` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSubstoichiometric inhibition of A\\xce\\xb21-40 aggregation by a tandem A\\xce\\xb240-1-Gly8-1-40 peptide\n\nPaper sections:\n1. INTRODUCTION\nThe aggregation of amyloid-\u00ce\u00b2 (A\u00ce\u00b2) is believed to be associated with the onset of Alzheimer's disease and there have been numerous studies of compounds that affect the aggregation process. A large number of compounds have been observed to inhibit aggregation and these have generally been grouped into three classes: those that inhibit oligomerization, those that inhibit oligomerization and fibrillization and those that inhibit fibrillization only (1-9). Among these studies, several investigators have used small peptides that would be expected to bind to full length A\u00ce\u00b2 but would be unable to form any structure that could serve as a template for subsequent monomer (or oligomer) addition (10,11). These latter studies were based on the observation of Tjernberg et al. (12) which suggested that the central region of the A\u00ce\u00b2 peptide (residues16-20) was responsible for the self-association and subsequent aggregation. These inhibitory peptides include those that are N-methylated (13,14) or cross-linked by a disulfide bond (15) or linked to an oligolysine (16). In general, such small peptides are indeed effective in preventing either oligomer formation or aggregation (17, 18) but the concentration of the peptide inhibitors required to prevent aggregation is high suggesting that the binding of the peptide is weak. Recently, Taylor et al. reported a class of retro-peptides which inhibited aggregation of either A\u00ce\u00b21-40 or A\u00ce\u00b21-42 at substoichiometric concentrations (19).
Here we report a novel approach to affect aggregation by using a tandem peptide consisting of two A\u00ce\u00b2 molecules linked by a glycine linker in such a way to give the tandem peptide construct NH2-A\u00ce\u00b240-1-(Gly)8-A\u00ce\u00b21-40-COOH. In this construct the N-terminal A\u00ce\u00b240-1 peptide has the reverse sequence of wild-type A\u00ce\u00b2 while the C-terminal A\u00ce\u00b2 peptide has the forward sequence.
\n\n2.1 Preparation of the Tandem peptide and A\\xce\\xb21-40\nIn our studies both A\u00ce\u00b21-40 and the tandem peptide were prepared as a fusion proteins as recently described by Garai et al. (20). The fusion protein of the tandem peptide was purified from inclusion bodies after dissolving in 6 M guanidine-HCl (GdnHCl), passed over a Ni2+-column and refolded on a Sephacryl S100 column in 25 mM HEPES with 100 mM NaCl at pH 7.5. The fusion protein eluted from the S100 column in two main fractions, one monomeric (60%) and the other multimeric (40%). Both fractions were treated with Factor Xa (New England Biolabs,USA) for 6 hrs at room temperature in 25 mM HEPES, pH 7.5 and 100 mM NaCl, using a ratio of Factor Xa to fusion protein of 1:100 (w/w). After cleavage, the peptide was precipitated with 200 \u00ce\u00bcM ZnCl2, dissolved in 6 M GdnHCl and purified by HPLC. The tandem peptide eluted at 33.5-35% in an acetonitrile gradient, was lyophilized and stored at -20 \u00c2\u00b0C. The yield of tandem peptide was 1mg/6L cell culture and showed a typical tyrosine fluorescence spectrum. Mass spectrometry of the purified material showed a single peak at a molecular weight of 9097.64 Da compared to the theoretical expected average isotopic mass of 9098 Da (supplementary figure S1). The peptide concentrations were measured by absorbance using values of 1450 M-1cm-1 and 2900 M-1cm-1 at 276 nm for A\u00ce\u00b21-40 and the tandem peptide, respectively.
\n\n2.2 Preparation of Peptide Solution and ThioflavinT assay\nThe time course of aggregation in the presence and absence of the tandem peptide was measured by Thioflavin T (Figure1). For these experiments, A\u00ce\u00b21-40 and the tandem peptide at concentrations of 200 \u00ce\u00bcM and 50 \u00ce\u00bcM respectively were dissolved in 5 mM NaOH. A 50 mM borate stock solution at pH 7.8 was then added to this solution to lower the pH to 8. The final concentration of borate buffer was kept at 25 mM. The solution was centrifuged at 14000g for 20-30 minutes and the supernatant solution was used for the experiments. Varying concentration of A\u00ce\u00b21-40 and the tandem peptide were incubated at 37 \u00c2\u00b0C and the extent of aggregation was measured by Thioflavin T.
For ThioflavinT assay, 20 \u00ce\u00bcl of the peptide solution was added in 1ml of glycine buffer (50 mM, pH 9.0) containing 10 \u00ce\u00bcM of ThioflavinT. Solutions were excited at 450 nm and emission was recorded at 490 nm. Before each reading a blank containing no peptide solution was taken to check the baseline. Between each reading the cuvettes were thoroughly rinsed with distilled water and dried to avoid any contamination.
\n\n2.3 Atomic Force Microscopy (AFM) of Amyloid fibrils\nFor AFM studies, 75 \u00ce\u00bcM A\u00ce\u00b21-40 in the presence and absence of 3 \u00ce\u00bcM tandem peptide was incubated for 4 days at 37 \u00c2\u00b0C in 25 mM borate buffer at pH 8.0. 5\u00ce\u00bcL of sample was diluted 20-fold with distilled water and allowed to settle on the freshly cleaved mica surface for 30 min. The majority of the solution was drawn off and the samples dried for 10-15 minutes in vacuo. The images were recorded using AFM MFP-3D-BIO (Asylum Research, Santa Barbara) with a scan resolution of 512\u00c3\u0097512 points/scan at a scan speed of 1 Hz.
\n\n2.4 Circular Dichroism Spectra of Tandem pepitide\nFor secondary structural analysis with CD, a tandem peptide stock solution (50 \u00ce\u00bcM) in 5 mM NaOH solution buffer was diluted 5-fold into 200 mM phosphate buffer at pH 8.0.The CD scans were recorded immediately after dilution using a Jasco J-715 spectropolarimeter. Ten scans from 200 to 260 nm with speed of 20 nm/minute were averaged. A buffer blank was performed under the same conditions and the final spectra were analyzed after buffer blank subtraction.
\n\n3.1 The ThioflavinT assay\nFigure 1A shows that the onset of fibrillization in the presence of the tandem peptide at a tandem pepide:A\u00ce\u00b21-40 molar ratio of 1:25 is delayed about 2-fold. At a tandem peptide:A\u00ce\u00b21-40 molar ratio of 1:10 (Figure 1B), no fluorescence increase is observed after 350 hrs compared to the fibrillization being complete by 175 hrs in the absence of the tandem peptide. The concentrations of A\u00ce\u00b21-40 used in these experiments are 50 \u00ce\u00bcM and 65 \u00ce\u00bcM respectively, while those of tandem peptides are 2 and 6.5 \u00ce\u00bcM, respectively. As a control experiment, two reference samples containing 2 \u00ce\u00bcM and 6.5 \u00ce\u00bcM of tandem peptide alone were kept under the same experimental conditions. Neither increase in ThioflavinT signal nor any precipitation was observed even after 12 days of incubation.
\n\n3.2 Atomic force Microscopy\nFigure 2 shows AFM images of A\u00ce\u00b21-40 in the absence and presence of tandem peptide at a 1:25 ratio. Figure 2A clearly shows large fibrils (~20 \u00ce\u00bcm in length) in the absence of the tandem peptide after 4 days of incubation while no fibril formation was observed in the presence of the tandem peptide (Figure 2B).
\n\n3.3 Circular Dichroism spectra of the Tandem peptide\nThe CD spectrum of the tandem peptide showed a characteristic minimum at 216 nm suggesting a high \u00ce\u00b2-sheet propensity (Figure 3). Interestingly, when the tandem peptide was kept for 4-5 days under these conditions at concentration ~10 \u00ce\u00bcM no increase in ThioflavinT signal was observed.
\n\n4. Discussion\nThe experimental results clearly indicate a sub-stoichoimeric inhibition of A\u00ce\u00b21-40 fibrilization by the tandem peptide. The present study represents a different and unique approach to study the aggregation mechanism of A\u00ce\u00b2. The results presented here not only suggest a mechanism for A\u00ce\u00b21-40 aggregation but also a general procedure for inhibiting other aggregation processes. The substoichiometric inhibition suggests first that the tandem peptide is binding to a form, presumably an oligomer, which is on pathway to form fibrils, and which is present in only low concentration. From the CD data, the tandem peptide shows a high \u00ce\u00b2-sheet propensity which might allow specific binding to an intermediate directly involved in fibrillization pathway. On the other hand, it is known that reverse sequence A\u00ce\u00b240-1 has different properties than that of normal A\u00ce\u00b21-40. For example, Giordano et. al., have suggested that both the nature of aggregates formed and the mechanism of toxicity differs between the peptides containing the forward and reverse sequences (21). The reverse sequence A\u00ce\u00b240-1 forms globular aggregates in contrast to the forward sequence which is fibrilar (21). This is indeed what we see in AFM when the tandem peptide aggregates at higher concentration (\u00e2\u0089\u00a5 25\u00ce\u00bcM) (supplementary figure S2).
Jan et al. (22) have shown that while A\u00ce\u00b21-40 appears to retard the formation of mature A\u00ce\u00b21-42 fibrils, the reverse sequence A\u00ce\u00b240-1 does not affect fibrillization of protofibrillar A\u00ce\u00b21-42 indicating the specificity of the interaction. Thus in the complex formed by tandem peptide and the on pathway oligomer(s) involved in fibrilization, the reverse sequence present in the tandem peptide may not allow monomer addition thereby preventing further aggregation.
\n\n5. Conclusion\nThese studies suggest a new approach for understanding the mechanism of fibrillization of intrinsically disordered proteins. Such studies are first of its kind and various permutation of such sequence attachment in A\u00ce\u00b2 is presently being pursued in our lab to check their effects on fibrilization. We are also currently in process of implementing tandem constructs in vivo to check its effect on aggregation of A\u00ce\u00b2 inside neuronal cells.
", "answer": "A\\xce\\xb2 peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer\\'s disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of A\\xce\\xb21-40 fibrillization as a tandem dimeric construct consisting of A\\xce\\xb240-1 (reverse sequence) linked to A\\xce\\xb21-40 via an eight residue glycine linker. At molar ratios of the tandem peptide to A\\xce\\xb21-40 of 1:10 to 1:25 inhibition of fibrillization, as measured by Thioflavin T, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.", "id": 2} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe are also grateful to darby proctor for useful comments on a previous version of the manuscript .\nthe present study was approved by the ethics committee of azabu university ( japan ) ( no .\n1303042 ) . this research was supported by the jsps research fellowships for foreign researchers ( no .\np10311 ) and the mext grant - in - aid for scientific research ( no .\n26380981 ) to t. r. , the mext grant - in - aid for challenging exploratory research ( no .\n23650132 ) to t. h. , and the grant - in - aid for scientific research on innovative areas ( no .", "answer": "in a recent paper,1 we examined whether oxytocin in the domestic dog modulates the maintenance of close social bonds in non - reproductive contexts . we found that exogenous oxytocin promotes positive social behaviors not only toward conspecifics , but also toward human partners . \n here we examined in further detail the effect that oxytocin manipulation has on social play . when sprayed with oxytocin , \n subjects initiated play sessions more often and played for longer periods of time than when sprayed with saline . furthermore , after oxytocin nasal intake dogs displayed play signals more often than after saline administration , suggesting that oxytocin enhances dogs ' play motivation . to our knowledge \n , this study provides the first evidence that oxytocin promotes social play in the domestic dog . \n we use these results to hypothesize on the potential therapeutic use of oxytocin for promoting social behaviors and treating social deficits in the domestic dog .", "id": 3} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe a : icr ( crl : cd1(icr ) ) and b : icr ( tac : icr ) mice were purchased from two different commercial laboratory animal breeding company in korea .\nthe mice were housed in a pathogene - free animal facility under a standard 12 h light / dark cycle , maintained in conventional housing conditions at 221 and 5010% relative humidity .\nall mice were provided with ad libitum access to standard irradiated chow diet ( purina rodent chow 38057 ) consisting of moisture ( 9.03% ) , crude protein ( 21.52% ) , crude fat ( 5.03% ) , crude fiber ( 4.33% ) , crude ash ( 6.31% ) , calcium ( 1.18% ) , and phosphorus ( 0.35% ) and drinking water .\nall animal procedures were conducted in accordance with guidelines of the institutional animal care and use committee , national institute of food and drug safety evaluation ( nifds , cheongju , korea ) .\nphylogenetic trees were constructed using the dnapars program of phylip ( phylogeny inference package ) version 3.695 ( http://evolution.genetics.washington.edu/phylip.html ) based on alignment of snps .\nseqboot and condense programs of the phylip package were used in bootstrap analysis of 100 resamplings of the data sets .\nmeasurement of body and organ weights was made based on the methods of the international mouse phenotyping consortium .\nhematological analysis was determined using by advia 2010i hematology system with autoslide ( siemens , germany ) .\nclinical chemical parameters were measured from a single serum sample using a hitachi 7100 automatic analyzer ( hitachi , japan ) .\nwe noticed that korl : icr had a significant increase in the litter size of the second litter as compared with the first litter .\ntherefore , the number of offspring of the first litter was taken as to litter size .\ntime to delivery represents the time period from mating to birth and fertility rate represents a ration between number of female mice giving birth and those used for mating .\ncages were observed three times per week and the number of pups born dead or alive and the number of pups weaned in each cage was recorded .\nstatistical changes in all data were determined using one - way analysis of variance ( anova ) .\nthe a : icr ( crl : cd1(icr ) ) and b : icr ( tac : icr ) mice were purchased from two different commercial laboratory animal breeding company in korea .\nthe mice were housed in a pathogene - free animal facility under a standard 12 h light / dark cycle , maintained in conventional housing conditions at 221 and 5010% relative humidity .\nall mice were provided with ad libitum access to standard irradiated chow diet ( purina rodent chow 38057 ) consisting of moisture ( 9.03% ) , crude protein ( 21.52% ) , crude fat ( 5.03% ) , crude fiber ( 4.33% ) , crude ash ( 6.31% ) , calcium ( 1.18% ) , and phosphorus ( 0.35% ) and drinking water .\nall animal procedures were conducted in accordance with guidelines of the institutional animal care and use committee , national institute of food and drug safety evaluation ( nifds , cheongju , korea ) .\nphylogenetic trees were constructed using the dnapars program of phylip ( phylogeny inference package ) version 3.695 ( http://evolution.genetics.washington.edu/phylip.html ) based on alignment of snps .\nseqboot and condense programs of the phylip package were used in bootstrap analysis of 100 resamplings of the data sets . the neighbor program of phylip\nmeasurement of body and organ weights was made based on the methods of the international mouse phenotyping consortium .\nhematological analysis was determined using by advia 2010i hematology system with autoslide ( siemens , germany ) .\nclinical chemical parameters were measured from a single serum sample using a hitachi 7100 automatic analyzer ( hitachi , japan ) .\nwe noticed that korl : icr had a significant increase in the litter size of the second litter as compared with the first litter .\ntherefore , the number of offspring of the first litter was taken as to litter size .\ntime to delivery represents the time period from mating to birth and fertility rate represents a ration between number of female mice giving birth and those used for mating .\ncages were observed three times per week and the number of pups born dead or alive and the number of pups weaned in each cage was recorded .\nstatistical changes in all data were determined using one - way analysis of variance ( anova ) .\nthe phylogenetic trees based on distance , the minimum genetic distance of korl : icr and other icr showed a genetic structure with three main clusters ( figure 1 ) . from these distance matrices , one can infer the nature of the identified stock differences and the genetic relationships between them .\nthis indicated that b stock has small genetic diversity compare with a stock and korl stock , and there is large genetic diversity between a stock and b stock .\nwe measured litter size , body weight , body length , various organ weight , hematology and clinical blood chemistry of the korl : icr compared to other icr .\nmouse phenotype analysis , body weight of korl : icr , a : icr and b : icr has been measured during the designated developmental periods ( 3 weeks to 12 weeks ) .\nkorl : icr and other icr mice experienced similar in body length as well ( figure 2b ) .\nfemale korl : icr mice were experiencing a significant increase in liver , heart and kidney weight compared to a : icr , but no difference with b : icr was observed ( figure 2c ) .\nmale korl : icr mice had a significant increase in liver , spleen and testis weight compared to a : icr ( figure 2d ) .\nthe mean litter size of korl : icr mice was 14.52.9 which was higher than commercial icrs ' ( table 1 ) . otherwise , there are no significant differences among the biological phenotypes of korl : icr and other icr .\nas summarized in table 2 , 3 , some hematological and biochemical parameters have been observed with sporadically significant differences .\nlaboratory mice are the essential resource to identify the potency and safety of the drugs and estimate the potency and adverse effects of drugs during the developing stage . according to the effectuation of the nagoya protocol , laboratory mice are not only indispensable for life science studies but also are being considered as important resource . among laboratory mice ,\nicr mice are most popular outbred mice broadly used in various fields like toxicology , oncology , pharmacology , pharmaceutical products safety test , and etc . .\nswiss mice , that were crossed in 1926 and then adopted by the institute of cancer research in 1974 ( subsequently merged with\ncommercial production of icr by companies began in 1959 , and the strain was made available to academic and commercial breeders .\ncurrently , many breeders worldwide have possessed their own icr stocks and the icr stocks have been reproduced for their academic or commercial purpose .\nthe opinions that there might be possible to have differences among icr mice already ensured in various regions of world which have been raised for long term and among mice of the identical stock bred by different breeders have been proposed in some point of view , but there are not sufficient evidences to support these yet .\neven though outbred mice are hard to realize the reliability and the repeatability , they are consider to be worked as better resource when the test result is applied to human due to the genetic diversity if compared to inbred mice .\nin addition , the advantage of using the icr stocks is extremely high in reproduction rate than the other outbred mice so that it may help the study cost effective .\nevery icr breeder has adopted and being bred these following common protocols : maintain icr stocks as long as possible , maintain genetic diversity as possible by composing multiple colonies , and minimize the genetic drift .\nthis study is carried out to establish scientific supports how different in aspect of normal growth curve , breed grad , and clinical blood chemical analysis to ensure the characterization data of icr stock mouse which have been bred by circulation breed approach for more than 50 years .\nthe breed capacity of both korl : icr mice and commercial icr mice were identified .\nthe mean litter size of the korl : icr mice were higher than other icr mice . between monthly litter size and litter size per number of pregnancy of the korl : icr mice did not experience a significant difference , but the size of second and third litter were higher than first and fourth litter ( data not shown ) .\nthe korl : icr mice were having median value of between a : icr and b : icr in a basic phenotype analysis . to tests\nevaluation of reactivity drugs , their behavioral changes were observed after administering caffeine and chlorpromazine which activates the central nervous system ; it was possible to identify that the recovery rate of the korl : icr was similar to other icr mice ( data not shown ) .\nkorl : icr was deduced that there was no significant difference with commercial icrs , and some weight gaps of the organs might be dependent the breeding condition ( feeds , the breeding place ) .\nsince the comparison studies on laboratory mice have not been remarkably activated , we have faced the difficulty of comparing the study result at this moment .\n( 2016 ) suggested that three icr groups , the korl : icr , a : icr and b : icr derived from different sources have an overall similar response of body weight , histopathological structure and inflammation to gastric ulcer inducers .\nalcohol induced ulcer model comparison assessment for reviewing the characteristics of the korl : icr were having similar result\n. however , the result would be more appropriate to compare with control group rather than the comparison of the absolute value because of a significant difference in certain enzymes .\nanother implication of the study is that references data ( breeding rate and basic phenotype ) regarding the korl : icr are secured and can be shared with the other researchers .\nthe korl : icr stocks have been used for decades in terms of conducting lot release project and more , in the national institute of food and drug safety evaluation . in conclusion , we will study secure general documents needed to have as mice resource through this accumulation of various experimental data .", "answer": "mouse is a commonly used animal in life science studies and is classified as outbred if genetically diverse and inbred if genetically homogeneous . \n outbred mouse stocks , are used in toxicology , oncology , infection and pharmacology research . \n the national institute of food and drug safety evaluation ( nifds ; former the korea national institute of health ) have bred icr mice for more than 50 years . \n we investigated to provide users with information and promote accountability to the korl : icr . to secure \n the indigenous data , biological characteristics of korl : icr were identified by comparing with other icr stocks . \n this domestic icr stock was denominated as \n korl : icr. phylogenetic analysis using snps indicated that the population stratification of the korl : icr was allocated different area with other icr . \n in addition , we measured litter size , body weight , body length , various organ weight , hematology and clinical blood chemistry of the korl : icr compared to other icr . \n otherwise , there are no significant differences among the biological phenotypes of korl : icr and other icr . \n these results suggest that as a genetically indigenous source colony , the korl : icr is seperated ( or independent ) stock with other icr . also , we confirmed that there is no difference among the korl : icr and other icr on biological phenotypes . \n therefore , the korl : icr source colony might be a new stock in distinction from other icr , it is a good milestone in securing ownership of the national laboratory animal resource . \n the nifds expects that the korl : icr mice will be useful animal resource for our domestic researchers .", "id": 4} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe analysis is based on food consumption data collected in nine european countries : denmark , finland , germany , ireland , italy , poland , spain , the netherlands , and united kingdom .\nthe data were collected by an international life science institute ( ilsi ) europe expert group ( 9 )\n. the selected micronutrients are vitamin a , retinol , vitamin d , vitamin e , niacin , vitamin b6 , folate , calcium , magnesium , iron , zinc , phosphorus , iodine , selenium , and copper .\ndata reflect intakes from natural sources plus mandatory fortification ( practiced in denmark , ireland , and poland ) other fortification and supplements are not included .\nthe survey methods comprise seven - day records or diaries with estimated or weighed amounts of foods ( denmark , ireland , italy , and uk ) and 24 ( poland ) or 48-hour recall ( finland , the netherlands , and spain ) .\ngermany used a modified diet history and the dutch and spanish recalls were supplied with semiquantitative food frequency questionnaires . the data from spain and the netherlands have been adjusted to correct for short registration period ( 9 ) . \n national dietary surveys with information on year , methodology , survey size , and age range intake of nutrients was calculated using national food composition databases .\nthe intake data provide data from four groups : children 410 years , children 1117 years , adult women , and adult men .\nthe analytical process included steps 2 and 3 of the following four steps for each of the selected vitamins and minerals and for each selected gender and age group : calculation of mean intakes from each of the dietary surveys ( an estimate of mean european intake).calculation of the ratio between the 95th percentile and mean intake in each survey.calculation of the average of the ratios.calculation of the common estimate for high intake as the product between steps 1 and 3 ( an estimate of european 95th percentile intake ) . \n \ncalculation of mean intakes from each of the dietary surveys ( an estimate of mean european intake ) .\ncalculation of the common estimate for high intake as the product between steps 1 and 3 ( an estimate of european 95th percentile intake ) .\naverage ratios for each country and the overall average arranged in ascending order are shown in table 2 .\nthe results show that for each nutrient the ratio has approximately the same value from one survey to another , implying that the ratio between high and average intake of micronutrients follows a regular pattern across countries and survey methods .\nthe polish ratios are systematically higher than those of the other countries due to the short registration period , which causes a wider intake distribution .\nthe spanish and to some extent also the dutch ratios are lower than the others probably because of adjustment of primary data . in the present analysis\naverage of ratios ( p95:mean intakes ) from national dietary surveys in nine european countries intake is not reported .\nnote : the overall average is based on ratios from all gender and age groups , i.e. normally four ratios from each country .\noverall , the ratios can be divided into three categories : one category with overall ratios of the 95th percentile and mean intake between 1.48 and 1.58 ; this range in ratios is close to the energy ratio ( 1.45 ) and includes the nutrients : magnesium , phosphorus , zinc , iron , vitamin b6 , niacin , and folate.another category has overall ratios in the range between 1.67 and 1.79 and includes the nutrients : calcium , selenium , vitamin e , iodine , and copper.a third category has overall ratios in the range of 2.072.32 and comprises the nutrients : vitamin a , vitamin d , and retinol.in table 3 , ratios of energy and micronutrients for young and older children , and adult females and males are presented .\nratios for the group of young children tend to be slightly lower than the ratios for adults .\nthe intake distributions of children aged 1117 years are wider and thus the ratios higher because of a wider range in energy requirements in this group .\nan exception from this tendency is the ratios of vitamin a , vitamin d , and retinol , which are lower than other group values . \n \none category with overall ratios of the 95th percentile and mean intake between 1.48 and 1.58 ; this range in ratios is close to the energy ratio ( 1.45 ) and includes the nutrients : magnesium , phosphorus , zinc , iron , vitamin b6 , niacin , and folate .\nanother category has overall ratios in the range between 1.67 and 1.79 and includes the nutrients : calcium , selenium , vitamin e , iodine , and copper .\na third category has overall ratios in the range of 2.072.32 and comprises the nutrients : vitamin a , vitamin d , and retinol .\naverage of ratios ( p95:mean intakes ) from all counties divided into age and gender groups note : figures in parentheses are the number of countries contributing to the average .\nthe results of the present study show that the ratio between high and mean intake for each micronutrient is fairly stable from one survey to another .\nthe similarity occurs despite differences in dietary habits across countries and despite several differences of methodological nature ( type of dietary survey , food composition data base , sampling procedure , etc . ) .\nthis similarity probably reflects the biological nature of eating and eating a variety of foods .\nwe divided the ratios into three rough categories in an attempt to explain the findings .\nsince most nutrients are widely distributed in rather low concentrations in many foods , their ratios are close to the ratio between the 95th percentile and mean energy intake ( category 1 ) . in category 2 ,\nintakes still follow energy intake but the intake distribution may be influenced by a few foods , which are important nutrient sources and has a skewed intake distribution , e.g. milk , which is the major source of calcium .\nthe third category includes highly skewed intake distributions due to only a few significant food sources of the micronutrient in question .\nthis effect may explain why the ratios for vitamin a , retinol , and vitamin d are lower among the children aged 1117 years than the three other groups , probably reflecting that most teenagers dislike fish , liver , and carrots foods very rich in these nutrients .\nthe only identifiable factors clearly affecting the ratios are the length of registration period and modification of primary data . because of the pragmatic purpose of this study and because excluding , i.e. polish data does not change the overall ratios much , we decided to accept all survey results .\nthe reason for this was the assumption that most underreporters are individuals found in the lower end of the intake distribution ( i.e. below mean intake ) and that the pattern of underreporting is the same in all populations . if the intakes of underreporters were increased to true levels , the intake distribution would be narrowed probably without any significant increase in levels of high intakes .\nthis means that the mean values will increase and the ratio p95/mean will be reduced .\nthe final product between the overall higher mean and lower ratio will be approximately unchanged .\nwe are fully aware of the limitations of the applied procedure where we used aggregated micronutrient data . with access to the individual data from each country\nbut even if the calculations are not mathematically ( statistically ) correct they will still create an estimate of high intake , which is sufficiently valid for the purpose of the present study .\nthe uncertainty is hardly any larger than that of results from any of the single surveys .\none could argue that simply calculating the average of 95th percentiles would be a more simple and direct way to a common estimate of high intake .\nthis is true and the results would probably be close to the results calculated via the ratios .\nanother argument against the present approach is the use of mean instead of median values . but using the ratio between 95th percentile and median did not change the final results ( results not shown ) and since it is important to find figures that will satisfy all member states in the eu , we suggest the use of mean values instead of median values . using the present method\nmakes it possible to include mean intake estimates from dietary surveys that are not able to describe the intake distribution .\nthis will allow us to use data from all or at least most european countries and thus increase the acceptability of the results across all eu member states .\nflynn et al . ( 4 ) used a different approach in their model for calculating safe additions to foods .\nthey expressed in each survey the high intakes ( 9097.5th percentiles ) as multiples of recommended intakes and used the mean of these multiples as a representative value .\nhowever , this method does not allow use of results from surveys giving only mean intakes . unfortunately the ilsi study does not provide data for all nutrients but we assume that the remaining vitamins and minerals will fit into a similar pattern\n. it still has to be shown based on dietary intake data whether this assumption is true , before the proposed model for calculating common european estimates for high intakes of all vitamins and mineral can be implemented in administrative practice .\nthe average ratio of the 95th percentile and the mean intakes of energy and micronutrients from foods show a remarkable similarity across countries and age groups . for each nutrient it\nis possible based on dietary surveys from different countries to calculate a representative european average .\nthe average ratio of the 95th percentile and the mean intakes is a simple and suitable measure for calculation of an estimate of high intake from an estimated average intake by the four steps described in the methods section .\nit is possible to include mean intake estimates from dietary surveys , which are not able to describe the intake distribution .\nthe authors declare that they have no conflict of interest and have received no funding for the present paper .", "answer": "background : a central element in establishing maximum amount of micronutrients in fortified foods and supplements is to reach to an agreement on how to estimate high intakes of vitamins and minerals from the european diet.objective:to examine whether ratios between the 95th percentile and mean intakes of vitamins and minerals show similarities across different countries independent of dietary habits and survey methods and if so , to suggest a simple and pragmatic way to calculate common estimates of high micronutrient intakes from foods.design:intake data of selected vitamins and minerals from nine european countries were examined for adult females and males and for children aged 410 and 1117 years . \n the ratios between the 95th percentile and mean intakes were calculated for each micronutrient , country , and age group.results:the ratios for each micronutrient follow a fairly regular pattern across countries and survey methods with differences between age groups.the nutrients fall into three categories : nutrients with ratios between 1.45 and 1.58 energy , magnesium , phosphorus , zinc , iron , vitamin b6 , niacin , and folate ; nutrients with ratios between 1.67 and 1.79 calcium , selenium , vitamin e , iodine , and copper ; nutrients with ratios between 2.08 and 2.32 vitamin a , vitamin d , and retinol.conclusion:sufficiently precise estimates of high micronutrient intakes across european countries can be reached by multiplying the overall average of ratios ( p95/mean intakes ) for each micronutrient with the corresponding mean intakes from all available dietary surveys in europe . \n this approach is a simple and pragmatic way to create common european estimates of high micronutrient intakes from foods .", "id": 5} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe beijing genotype is commonly present in russian population and in eurasia as a whole .\nthis lineage , especially bo\\w subline is characterized by high - level virulence , , , . for our analysis , we chose the mycobacterium tuberculosis strain b9741 , isolated from a 33-years - old hiv - positive female patient from irkutsk oblast , russia , with firstly diagnosed fibrocavernous tuberculosis , provided by the scfhhrp , irkutsk , russia .\nthis strain was resistant to isoniazid ( inh ) , rifampin ( rif ) , streptomycin ( sm ) and pyrazinamide ( pza ) .\ngenome sequencing was carried out on roche 454 gs junior instrument ( roche , switzerland ) , in the laboratory of bacterial genetics , vigg ras ( moscow , russia ) .\nall reads were assembled to an initial draft genome : 4,322,170 bp ( total length ) nucleotides at 13-fold coverage using the gs de novo assembler ( version 3.0 ; roche ) ( table 1 ) .\nthe automatic functional annotation results were obtained using ncbi prokaryotic genome annotation pipeline ( pgaap ) ( http://www.ncbi.nlm.nih.gov/genomes/static/pipeline.html ) .\nthe b9741 genome contains 4193 genes ( total ) , 4 rrnas , and 46 trnas .\na total of 250 pseudogenes , 3 noncoding rnas ( ncrnas ) , 1 clustered regularly interspaced short palindromic repeats ( crispr ) were predicted using the pgaap . according to housekeeping gene and toxin - antitoxin analysis , , we classified this strain to belong to b0/w beijing lineage .\nwe compared our output sequence with dna sequence of the high - virulent m. tuberculosis w-148 strain which belongs to b0/w cluster of beijing group . in this announcement , we focused on genes , which determine virulence and drug resistance .\nin addition , we analyzed snps in genes , which are associated with drug resistance to inh , rif , sm , and pza .\nanalysis we provide the comparison of sequenced dna with b0\\w dna sequences and revealed the presence of three polymorphisms at virulence genes .\nin the gene mce3f , which essential for survival of mtbs in macrophages and invasion to the host cells , we have found substitution - d410a , in irtb gene , which encode the part of irtab iron importer - a175 t , .\nthis protein play an essential role for iron homeostasis in stress conditions . and in vapc46 - a38 g , .\nthus , identified genes will be used for understanding of m. tuberculosis adaptation to patients with low immune level , including hiv + patients .\nothis whole genome shotgun ( wgs ) project has been deposited at genbank under the accession lvjj01000000 ( mycobacterium tuberculosis strain b9741 ) .\nthis whole genome shotgun ( wgs ) project has been deposited at genbank under the accession lvjj01000000 ( mycobacterium tuberculosis strain b9741 ) .\nthe beijing genotype is commonly present in russian population and in eurasia as a whole .\nthis lineage , especially bo\\w subline is characterized by high - level virulence , , , . for our analysis , we chose the mycobacterium tuberculosis strain b9741 , isolated from a 33-years - old hiv - positive female patient from irkutsk oblast , russia , with firstly diagnosed fibrocavernous tuberculosis , provided by the scfhhrp , irkutsk , russia .\nthis strain was resistant to isoniazid ( inh ) , rifampin ( rif ) , streptomycin ( sm ) and pyrazinamide ( pza ) .\ngenome sequencing was carried out on roche 454 gs junior instrument ( roche , switzerland ) , in the laboratory of bacterial genetics , vigg ras ( moscow , russia ) .\nall reads were assembled to an initial draft genome : 4,322,170 bp ( total length ) nucleotides at 13-fold coverage using the gs de novo assembler ( version 3.0 ; roche ) ( table 1 ) .\nthe automatic functional annotation results were obtained using ncbi prokaryotic genome annotation pipeline ( pgaap ) ( http://www.ncbi.nlm.nih.gov/genomes/static/pipeline.html ) .\nthe b9741 genome contains 4193 genes ( total ) , 4 rrnas , and 46 trnas .\na total of 250 pseudogenes , 3 noncoding rnas ( ncrnas ) , 1 clustered regularly interspaced short palindromic repeats ( crispr ) were predicted using the pgaap . according to housekeeping gene and toxin - antitoxin analysis , , we classified this strain to belong to b0/w beijing lineage .\nwe compared our output sequence with dna sequence of the high - virulent m. tuberculosis w-148 strain which belongs to b0/w cluster of beijing group . in this announcement\nwe developed the catalog of 342 genes determinate virulence , , . for this analysis ,\nin addition , we analyzed snps in genes , which are associated with drug resistance to inh , rif , sm , and pza .\nwe provide the comparison of sequenced dna with b0\\w dna sequences and revealed the presence of three polymorphisms at virulence genes .\nwe carried out a deeper analysis of these genes involved in virulence . in the gene mce3f ,\nwhich essential for survival of mtbs in macrophages and invasion to the host cells , we have found substitution - d410a , in irtb gene , which encode the part of irtab iron importer - a175 t , .\nthis protein play an essential role for iron homeostasis in stress conditions . and in vapc46 - a38 g , .\nthus , identified genes will be used for understanding of m. tuberculosis adaptation to patients with low immune level , including hiv + patients .\nothis whole genome shotgun ( wgs ) project has been deposited at genbank under the accession lvjj01000000 ( mycobacterium tuberculosis strain b9741 ) .\nthis whole genome shotgun ( wgs ) project has been deposited at genbank under the accession lvjj01000000 ( mycobacterium tuberculosis strain b9741 ) .\nthe authors declare that there is no conflict of interests with respect to the work published in this paper .\nthis research did not receive any specific grant from funding agencies in the public , commercial , or not - for - profit sectors .", "answer": "we report a draft genome sequence of mycobacterium tuberculosis strain b9741 belonging to beijing b0/w lineage isolated from a hiv patient from siberia , russia . \n this clinical isolate showed mdr phenotype and resistance to isoniazid , rifampin , streptomycin and pyrazinamide . \n we analyzed snps associated with virulence and resistance . \n the draft genome sequence and annotation have been deposited at genbank under the accession nz_lvjj00000000 .", "id": 6} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute acalculous cholecystitis ( aac ) is defined as acute inflammation of the gallbladder in the absence of gallstones and has a multifactorial pathogenesis.1 aac occurs in about 10% of all cases of acute cholecystitis .\naac has numerous causes that produce bile stasis and ischemia leading to inflammation and infection of the gallbladder .\naac tends to have a more fulminant course , is frequently associated with gangrene , perforation and empyema , and has high morbidity and mortality.2 aac has traditionally been recognized to occur in patients with serious co - morbid illnesses especially after a major operation , severe trauma , burns , systemic sepsis and prolonged intravenous hyperalimentation.3 however , there has recently been an increasing number of reports in the literature of the occurrence of aac in patients with none of the established risk factors.4 - 6 aac arising as a complication of laparoscopic appendectomy has been reported in just 1 case and it was treated conservatively.7 herein , we present the case of a 38-year - old woman who developed aac after laparoscopic appendectomy .\na 38-year - old woman who was previously in good health came to our emergency room 3 days after she received laparoscopic appendectomy at a local clinic .\nshe had acute abdominal pain which initially occurred in the epigastric and umbilical area and then migrated to the right lower quadrant after 10 hours and was associated with nausea and anorexia .\nacute appendicitis had been diagnosed by abdominal computed tomography ( ct ) and operative findings at another hospital . her abdominal pain and associated symptoms improved after surgery .\nbody temperature was 37.8. she exhibited tenderness and guarding in the epigastric region and right upper quadrant .\nresults of the laboratory studies were unremarkable , except for elevated c - reactive protein ( crp ) which was 8.04 mg / dl ( normal range less than 0.5 mg / dl ) .\nher body mass index ( bmi ) was 21.7 ( height : 168 cm , weight : 61.2 kg ) .\nabdominal ct showed a thickened , contrast - enhanced wall of the gallbladder ( fig .\nher abdominal pain subsided and crp decreased to 1.33 mg / dl after the ptgbd .\nthe patient 's postoperative progress was uneventful , and she was discharged 5 days after surgery .\naac generally occurs in patients after major surgery , in the presence of critical illnesses such as trauma , burns , and sepsis , and in the elderly.1 however there have been recent reports of acalculous cholecystitis in young healthy patients who had none of the established risk factors.6,8 the patient described in this case report was young and healthy and exhibited none of the standard risk factors other than recent surgery , although laparoscopic appendectomy is not considered to be a major operation .\nthe commonest postulated pathogenesis of aac is bile stasis resulting in a change of bile composition and ischemia.2 factors known to contribute to bile stasis in the postoperative patient are fasting , anesthesia , dehydration , fever , and narcotics for the relief of pain.9 i believe that the most probable mechanism of aac in this woman was bile stasis that resulted from the anesthesia given to her during the appendectomy and the narcotics given for the relief of pain .\naac is difficult to diagnose because clinical signs such as abdominal pain and fever , and laboratory test results are non - specific .\ndelayed diagnosis of aac is associated with high morbidity and mortality due to the high prevalence of gangrene and perforation.10 early diagnosis and appropriate treatment can improve outcomes in patients with aac.11 the treatment options for aac are cholecystostomy and/or cholecystectomy.9,12 cholecystectomy generally is considered the definitive therapy , and percutaneous cholecystostomy can be performed safely and rapidly.9 standard treatment methods of aac have not yet been established , but it is usually determined by the patient 's condition .\ni believe that early cholecystectomy in this case was an effective treatment tool for avoiding potential failure of conservative management and for preventing recurrence , although the patient was young and had none of the risk factors . as mentioned above , laparoscopic appendectomy may mask clinical signs and symptoms of aac .\ntherefore , when right upper quadrant pain , fever , leukocytosis , and abnormal liver function tests are observed after surgery , physicians should consider the possibility of aac , and promptly check radiological findings .\naac arising as a complication of laparoscopic appendectomy has been reported rarely , especially in young healthy patients .\nwhen abdominal pain , leukocytosis , fever and abnormal results of liver function tests are observed in patients after appendectomy , the possibility of aac should be considered .\nprompt recognition and appropriate treatment of aac is necessary to minimize the associated morbidity and mortality .", "answer": "acute acalculous cholecystitis ( aac ) is defined as acute inflammation of the gallbladder in the absence of gallstones . \n aac occurs in patients after major surgery and in the presence of serious co - morbidities such as severe trauma , burns , sepsis , prolonged intravenous hyperalimentation and hemodynamic instability . \n aac is rare in patients with none of the established risk factors . \n we present a case of a 38-year - old woman who developed aac after laparoscopic appendectomy .", "id": 7} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nresin - based composites are used worldwide in dentistry , mainly because of their aesthetic quality and good physical properties .\nsince resin composites were first developed , many efforts have been made to improve the clinical behaviour of this restorative material .\nseveral studies have demonstrated that the degree of polymerization of light - cured resin composites depends on many parameters , such as , the specific formulation ( i.e. type and relative amount of monomer , filler and initiator / catalyst ) , the wavelength distribution , the intensity of the incident light and the irradiation time .\nalthough both organic and inorganic phases might influence the material behaviour , the filler particles features and rate of curing are the most important factors related to an improvement in the mechanical properties of the resin composites .\nthe intended areas of usage of resin composites have traditionally included a trade - off between composites polish ability and strength , based on filler size and loading .\nrecently , resin composites have been classified according to their filler particle size as hybrid ( 0,5 - 3 m ) , microhybrid ( 0,4 - 1 m ) and microfilled ( 0,04 - 0,4 m ) .\nmore recently , however , with the introduction of nanotechnology in dentistry , a new class of resin composite , the nanofilled composite resin , is available to clinicians , in an endeavour to provide a material presenting high initial polishing ability combined with superior polish and gloss retention .\nthe degree of cure of visible light activated dental resins was recognized as important to the clinical success of these materials soon after these materials were introduced .\na curing light intensity output depends on many factors ( light guide , condition of the bulb , battery life ) and the total energy determines the mechanical properties of the resin composites .\nalso , the distance of the light from the the resin composite is a crucial factor . in the last few years , curing light technology has advanced with the introduction of high intensity halogen lights , plasma arc lights and light emitting diode units ( leds ) , with the aim of fast curing of resin composites and generating less heat . led curing lights\nhave recently become very popular since they have a number of advantages over conventional halogen units .\ntraditional modes use high initial irradiance and provide a higher degree of conversion ( dc ) ; on the other hand , a higher shrinkage stress may be induced during polymerization reaction .\ngradual polymerization modes have been introduced in order to minimize polymerization shrinkage and consequent marginal gap formation .\nphysical properties of composite resin are also dependent on the dc of the resin matrix .\na positive correlation has been demonstrated between increasing hardness and increasing dc ; however , it was concluded that an absolute hardness number could not be used to predict dc when different resin composites are compared .\na previously published study showed a significant correlation between the degree of conversion and hardness , modulus of elasticity and flexural strength of dental restorative resins .\ndirect methods that assess the degree of conversion , such as infrared spectroscopy and laser raman spectroscopy , have not been accepted for routine use as they are complex , expensive and time consuming .\nincremental surface hardness has been shown to be an indicator of the degree of conversion and a good correlation between knoops hardness and infrared spectroscopy has also been reported .\nit has been used to predict the wear resistance of a material and its ability to abrade or be abraded by opposing tooth structures . to define depth of cure based on top and bottom hardness measurements , it is common to calculate the ratio of bottom / top hardness , and give an arbitrary minimum value for this ratio . in order to consider the bottom surface as adequately cured ,\nthe current in vitro study evaluated vickers hardness ( vk ) and depth of cure ( hardness ratio ) of three microhybrid , two nanohybrid and one nanofilled resin composites , polymerized with a led curing unit by three different polymerization modes .\nsix resin composites were selected for the present study and were chosen in accordance with their type of filler particles : three microhybrid ( esthet.x hd , amaris , filtek silorane ) , two nanohybrid ( grandio , ceram.x mono ) and one nanofilled ( filtek supreme xt ) .\nthe materials evaluated and their manufacturers are shown in table 1 . during the whole experimentation ,\nthe resin composites were light cured with a led unit , celalux ii ( voco , cuxhaven , germany ) .\nthree light polymerization modes were used for each material : standard 20 s : 1000 mw / cm for 20 seconds ; standard 40 s : 1000 mw / cm for 40 seconds ; soft - start 40 s : 0 to 1000 mw / cm for 5 seconds + 1000 mw / cm for 35 seconds . the hardness testing methodology used to assess\nsamples of the respective materials were prepared by placing the material into a stainless steel mold ( 7 mm , h 2 mm ) , and were placed on a dark opaque paper background covered with a polyester matrix strip .\nthe mold was filled with the resin composite and a second polyester matrix strip was placed on the top of the filled mold .\na glass slide was pressed against the upper polyester film to extrude the excess resin composite and to form a flat surface .\nthe distal end of the light guide was placed against the surface of the matrix strip and positioned concentrically with the mold ; and , the material was then light - cured from the top .\nmaterials used in the study and their manufacturers the cordless curing unit was maintained at full charge before use , and irradiance was checked with a radiometer ( led radiometer , kerr , orange , ca , usa ) .\nafter polymerization , the samples were stored for 48 hours in complete darkness at 37c and 100% humidity before the vickers hardness test ( vk ) .\nthe vickers hardness ( vk ) of the surface was determined with a microhardness tester ( durometer zhu 0,2 zwick - roell , ulm , germany ) using a vickers diamond indenter and a 200 g load applied for 15 seconds .\nfive vk readings were recorded for each sample surface ( top and bottom ) ; and the measurements were made in a sequential pattern , starting with the bottom surface of all specimens , and in 1 mm increments from the specimen centre and extending 2 mm in both x ( east - west [ e - w ] ) and y ( north - south [ n - s ] ) axes .\nhardness measurements were not taken at more than 4 mm from the specimen centre to avoid any possible effect of the mold on polymerization . for a given specimen ,\nthe five hardness values for each surface were averaged and reported as a single value .\nthe mean vickers hardness and hardness ratio of the specimens were calculated and tabulated using the formula : hardness ratio = vk of bottom surface / vk of top surface .\nthe mean vickers hardness of top and bottom surfaces and hardness ratio associated with the standard 20 s polymerization mode is shown in table 2 .\nthe mean vickers hardness of top and bottom surfaces and hardness ratio associated with the standard 40 s polymerization mode is shown in table 3 .\nthe mean vk of top and bottom surfaces and hardness ratio associated with the soft - start 40 s polymerization mode is shown in table 4 .\nthe influence of three curing modes ( standard 20 s and 40 s and soft - start 40 s ) on hardness ratio of six composite resins was compared . according to statistical analysis ( t student test ) , it was observed that for all the materials there was no statistical difference ( p > 0.5 ) in hardness values recorded on top surfaces .\na statistical significant difference ( p < 0.01 ) was recorded on the bottom surfaces for all the materials tested ; and this is due to the reduced energy reaching the lower layers , thus affecting the final hardness .\nmean vickers hardness of top and bottom surfaces and hardness ratio recorded with the standard 20 s polymerization mode as seen in the study mean vickers hardness of top and bottom surfaces and hardness ratio recorded with the standard 40 s polymerization mode as seen in the study mean vickers hardness of top and bottom surfaces and hardness ratio recorded with the soft - start 40 s polymerization mode as seen in the study hardness ratio values for the different polymerization modes as seen in the study despite this drastic difference between the values recorded on the top and bottom surfaces for all the materials , hardness ratio was higher than the minimum value indicated in literature in order to consider the bottom surface as adequately cured ( 0.80 ) . a statistically significant difference ( p < 0.01 )\nwas recorded comparing standard 20 s polymerization mode with both standard 40 s and soft - start 40 s polymerization modes for esthet.x hd , amaris and ceram.x mono .\ncomparing standard 40 s and soft - start 40 s polymerization mode , there was no statistical difference between hardness values recorded on top and bottom surfaces .\nresin composites are widely used in restorative dentistry and specifically in posterior restorations , putting the material under constant masticatory stresses .\none of the most important parameters deciding the resin composites resistance to stress is the depth of cure .\nthe effectiveness of cure depends on the filler particle type , size , quantity and on the parameters ( intensity , time and polymerization modes ) of the light source .\neffective cure of light - activated composites is also important to prevent cytotoxicity of inadequately polymerized material .\nthe optimal degree of curing throughout the bulk of a visible light - activated dental resin composite is acknowledged to be important to the clinical success of a resin composite restoration .\nunfortunately , the dentist has no means of monitoring the cure of the resin surfaces not directly exposed to the curing light .\nstated that one brand of composite in flowable , hybrid and packable formulations did not achieve a 2 mm depth of cure with 20 s light exposure . de jong et al . demonstrated that with high intensity light - curing units , exposure times of 10s/2 mm increment can be sufficient to obtain under in vitro conditions a high degree of conversion .\nthese data suggest that a 2 mm buildup layering technique may not result in adequate curing of the bottom layer for such a wide range of materials and that manufacturers need to provide quantitative information about the degree of conversion at specific activation times and light intensities for their entire range of resin materials and shades so that the dentist can devise a placement technique that will ensure adequate cure of the bulk of a restoration .\nthese findings where in disagreement with some studies that have shown that 2-mm increments were well polymerized .\nconcluded that the bottom - to - top surface microhardness ratios of a composite resin proved to be an accurate reflection of bottom - to - top degree of conversion ; bottom - to - top microhardness ; and , degree of conversion were independent of composite composition .\nthe development of new technologies and polymerization modes for photo - activation of restorative composite resins has also caused a great interest among researchers .\nhowever , the real advantages of these techniques are not yet totally known . in the present study , 2-mm thick composite specimens were used as it ensured uniform and maximum polymerization .\nthe degree to which light - activated composites polymerize is proportional to the amount of light to which they are exposed .\nideally , the degree of polymerization of the composite should be the same throughout its depth and the hardness ratio should be very close or equal to one .\nas light passes through the composite , the light intensity is greatly reduced due to light scattering , thus decreasing the effectiveness of cure at the bottom surface .\nit was suggested that the hardness ratio should be greater than 0.8% for light activated composites to be adequately polymerized . in the present study ,\nthe hardness ratio for all the tested materials was over 0.8% for standard 20 s and 40 s and soft - start 40 s polymerization .\ndenehy et al . found that the top surface hardness of composites was less dependent on light intensity than the bottom surface .\nthe top surface is actually receiving the maximum energy from the curing light . a statistically significant difference ( p < 0.01 )\nwas recorded comparing standard 20 s polymerization mode with both , standard 40 s and soft - start 40 s polymerization modes , at top and bottom surfaces , for esthet.x hd , amaris and ceram.x mono .\nthese results depend on the total amount of energy reaching the composite layer and on chemical composition of the composites . at the the top surface\n, it has also been established that even relatively low intensity lights can cure the resin matrix to an extent almost equal to when high intensity lights are used .\nthe general lack of significance between standard 40 s and soft - start 40 s curing modes in top vickers hardness found in this study corroborate the mentioned studies . at the top surface\n, sufficient light energy reaches the photoinitiator , thus starting the polymerization reaction . at the bottom surfaces , a significant difference in vk\nwas observed for all the materials , but no statistical difference was observed between standard 40 s and soft - start 40 s polymerization modes .\nthis may be due to the very fast increase ( 5 s ) of light intensity in soft - start polymerization , while total light exposure was very similar between the two polymerization modes . about the properties of the composite resins , the results were generally dependent on the material evaluated , especially with regard to filler features .\nsuggested that no trend towards the size or shape of fillers affected hardness ; and all materials generally presented different results in comparison with one another .\ngrandio , for instance , presented the highest values , probably because of its large particles and the highest filler content .\nnanofilled filtek supreme xt showed significantly higher hardness values than esthet.x hd , filtek silorane and ceram.x mono , which were all conceived for posterior restorations . in this study\n, only one physical property was tested on a limited number of composite resins polymerized with one type of unit .\nmore research involving the use of other materials and multiple combinations of polymerization modes is warranted .\ncuring time did not affect hardness ratio values for filtek silorane , grandio and filtek supreme xt .\nthe effectiveness of cure at the top and bottom surface was not affected by soft - start polymerization mode .", "answer": "aim : the current in vitro study evaluated vickers hardness ( vk ) and depth of cure ( hardness ratio ) of six resin composites , polymerized with a light - emitting diode ( led ) curing unit by different polymerization modes : standard 20 s , standard 40 s , soft - start 40 s.materials and methods : six resin composites were selected for the present study : three microhybrid ( esthet.x hd , amaris , filtek silorane ) , two nanohybrid ( grandio , ceram.x mono ) and one nanofilled ( filtek supreme xt ) . \n the vk of the surface was determined with a microhardness tester using a vickers diamond indenter and a 200 g load applied for 15 seconds . \n the mean vk and hardness ratio of the specimens were calculated using the formula : hardness ratio = vk of bottom surface / vk of top surface.results:for all the materials tested and with all the polymerization modes , hardness ratio was higher than the minimum value indicated in literature in order to consider the bottom surface as adequately cured ( 0.80 ) . \n curing time did not affect hardness ratio values for filtek silorane , grandio and filtek supreme xt.conclusion:the effectiveness of cure at the top and bottom surface was not affected by soft - start polymerization mode .", "id": 8} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe applied the blastp program ( 5 ) to identify , for each predicted protein sequence in the h37rv genome ( genbank accession no .\nae000516 ) . following genbank annotations , we compared 3,972 predicted proteins in h37rv with 4,187 predicted proteins in cdc1551 .\nwe used a strict search criterion ( e = 10 - 50 ) to identify truly orthologous gene pairs .\nwe aligned ( 6 ) the putative orthologous pairs of amino acid sequences ( n = 3,428 ) , then imposed this alignment on the dna sequences .\nvisual inspection of amino acid alignments showed that certain alignments , usually near the n - terminus or c - terminus , had regions of very low sequence identity .\nexamination of the dna sequences of the corresponding genes showed that these regions of low identity were typically caused by a frameshift in one of the two genomes relative to the other .\nwhether these frameshifts are biologically real or result from sequencing error was uncertain ; therefore , we eliminated 119 such gene pairs from our data set .\nfor the remaining gene pairs ( n = 3,309 ) , we computed the proportion of synonymous substitutions per synonymous site ( ps ) and the proportion of nonsynonymous substitutions per site ( pn ) by using nei and gojobori s method ( 7 ) . because values of ps and pn were very low in most cases , we did not correct for multiple hits . because ps values appeared to fall into two groups ( see results ) , we used a simple probabilistic model to separate these two sets of gene pairs .\nwe assumed that the probability of synonymous substitution followed two separate binomial distributions , designated models a and b , with probabilities of success \n( i.e. , of a synonymous difference ) designated pa and pb , respectively . using the bayes equation , for each gene pair with a given ps value ,\nwe computed the probability that model a applies , given the observed ps : p(a|ps ) = ( psa ) fa /[(psa ) fa + ( psb ) fb ] , where fa is the frequency of cases to which model a applies , fb the frequency of cases to which model b applies , psa is the binomial probability of obtaining the observed ps , given the number of synonymous sites in the gene and a probability of a synonymous difference equal to pa ; and psb is the binomial probability of obtaining the observed ps , given the number of synonymous sites in the gene and a probability of a synonymous difference equal to pb .\nof 3,309 pairs of putatively homologous protein - coding genes in the h37rv and cdc1551 genomes of m. tuberculosis , 2,662 ( 80.5% ) showed no synonymous or nonsynonymous nucleotide differences between the two genomes , and 3,010 ( 91.0% ) showed no synonymous differences between the two genomes .\nhowever , in a small number of gene pairs , the proportion of synonymous differences per synonymous site ( ps ) was surprisingly high . in 13 ( 0.4% )\ngene pairs , ps was > 0.01 , and in 3 gene pairs ps exceeded 4% .\nthese extreme ps values seen in a small number of gene pairs are much higher than generally observed between alleles at neutrally evolving loci in eukaryotes ( 8) .\nthus , the comparison of protein - coding genes between the two m. tuberculosis genomes suggested the existence of two distinct groups of gene pairs : a large group having few or no synonymous differences and a much smaller group with a substantial degree of synonymous divergence .\nwe used a simple probabilistic model ( see methods ) to separate these two sets of gene pairs , designated group a and group b , respectively ( figure ) .\nthe application of this method showed 11 loci with unusually high ps values and probabilities of assignment to group a of < 50% ( figure ) .\na plot of p(a|ps ) , the probability of assignment of a locus to group a given the observed ps value , as a function of ps at 3,309 loci compared between the h37rv and cdc1551 genotypes of mycobacterium tuberculosis .\nthe plot shows the bimodal nature of the distribution of ps values , with overall higher values of ps at the 11 loci having p(a|ps ) > 50% .\nwe assumed that group a members are truly orthologous gene pairs that diverged at the time of the common ancestor of the h37rv and cdc1551 genomes .\ngroup a included 3,298 pairs , with mean ps for all genes of 0.000328 0.000022 standard error .\nwhen ps was estimated for the 3,298 genes concatenated together ( a total of 934,413 synonymous sites ) , an estimate of ps = 0.000348 0.00019 was obtained .\nthe range of ps values in group a was between zero and 0.012 ; a total of 288 loci in group a had ps values other than zero .\nthese results show a substantial level of nucleotide diversity , approximately half the level of nucleotide diversity in humans ( 9 ) .\nrates of nucleotide substitution per unit time are difficult to estimate in bacteria given the lack of calibration from the fossil record ( 10 ) . to obtain an estimate of the rate of synonymous nucleotide substitution ,\nwe used published data on comparisons of escherichia coli and salmonella typhimurium ( 11,12 ) , which are believed to have diverged approximately 100 million years ago ( 13,14 ) ( table 1 ) .\nthis procedure yielded estimates for the last common ancestor of h37rv and cdc1551 in the range of 34,00038,000 years ( table 1 ) .\nthese estimates are approximately twice previous estimates of the age of the common ancestor of worldwide m. tuberculosis ( 2,3 ) . to obtain the observed mean ps value between h37rv and cdc1551 within 15,00020,000 years would require a rate of synonymous substitution approximately twice that observed in enterobacteria . based on synonymous substitutions between escherichia coli and salmonella typhimurium , assumed to have diverged 100 million years ago ( 13,14 ) . \nestimates are shown standard error , based on standard error of mean ps . \ngroup b consisted of 11 gene pairs with mean ps of 0.0286 0.0050 ( table 2 ) . paired sample t - test of the hypothesis that ps = pn , p<0.01 .\nthe quantities ps and pn are the proportion of nucleotide difference per synonymous site and per nonsynonymous site , respectively . in enterobacteria , a negative correlation exists between observed proportions of synonymous difference and codon bias ( 11 ) . in the case of mycobacterium ,\ncodon bias results mainly from the very high third position g+c content of most genes ( 15 ) . in our data , however , we observed no correlation between ps and proportion g+c at third codon positions ( r = -0.010 ; not significant ) .\na number of additional possibilities may explain the occurrence of gene pairs with higher than expected ps values : 1 ) balanced polymorphism .\nselectively maintained polymorphisms are expected to be much older than neutral polymorphisms and may even predate speciation events ( 16 ) . in the case of haploid organisms such as bacteria\n, balancing selection would take the form of frequency - dependent selection rather than overdominant selection .\n2 ) differential deletion . in a multi - gene family , if one member of an orthologous pair of genes were deleted in one genotype , the gene pairs would involve paralogous , not orthologous comparisons .\n3 ) horizontal gene transfer . a gene obtained by one of the two genotypes from another bacterial species\none indication of a balanced polymorphism is a higher rate of nonsynonymous than synonymous substitution ( 8) . there was no strong evidence of such selection in the present case ; ps was greater than pn at 10 of the 11 loci , and pn exceeded ps only slightly at one locus ( table 2 ) .\nin addition , we compared ps and pn in sliding windows of 30 codons along the length of these genes .\nno regions were observed in which pn was greater than ps ( data not shown ) .\nthus , there was no evidence of positive selection acting on specific regions of these genes .\non the other hand , differential deletion can probably explain some cases , most notably members of the pe multi - gene family ( 11 ) ( table 2 ) .\nthe remaining gene pairs are possibly cases of horizontal gene transfer ( table 2 ) , for which there is some recent evidence in m. tuberculosis ( 17 ) .\nour results did not support the hypothesis that the common ancestor of m. tuberculosis was relatively recent ( 2 ) .\nrather , the pattern of nucleotide substitution at synonymous sites suggested a divergence time for the two available genotypes of this species approximately 35,000 years ago .\nsince h37rv and cdc1551 represent two genotypes sampled from within the species , they are probably not the most divergent genotypes possible .\nthus , the last common ancestor of m. tuberculosis likely occurred considerably earlier than 35,000 years ago .\nwhile the difference between an estimate of 15,00020,000 years and one of 35,000 years is not large on an evolutionary time scale , such a difference is substantial on the scale of human history .\nfor example , the existence of two genotypes in the current population of m. tuberculosis with a common ancestor at 35,000 years is evidence against the hypothesis that m. tuberculosis arose , presumably from m. bovis , at the time of human domestication of cattle ( 18 ) .\nour result is thus consistent with phylogenetic analyses based on insertion - deletion events , which suggest that the m. tuberculosis lineage was a human pathogen well before the origin of m. bovis ( 19 ) .\nthus , along with recent evidence of an ancient origin and extensive polymorphism in the malaria parasite plasmodium falciparum ( 20,21 ) , our study provides evidence against the long - held view that virulent pathogens are invariably evolutionarily recent ( 22 ) .\nour estimate is conservative because the rate of synonymous substitution may actually be lower in mycobacterium than in enterobacteriaceae , given the highly skewed g+c content in the former .\nfurthermore , our estimate of the mean proportion of synonymous difference was conservative because we excluded 119 loci with potential frameshifts between the two genotypes as well as a set of 12 loci with unusually high ps values .\nin addition to the 12 loci assigned to our group b , certain other loci might also have originated from horizontal gene transfer . however , even if horizontal gene transfer has occurred at other loci besides those in group b , eliminating further loci with relatively high ps values from group a will not affect the results greatly .\nfor example , if we eliminate the 10 loci with highest ps values from group a , mean ps will be reduced only to 0.000299 , and the estimated age of the common ancestor will be barely affected .\nthe degree of polymorphism observed in this study is unlikely to have been substantially influenced by sequencing errors .\nthe error rate for finished sequences from the institute for genomic research ( where cdc1551 was sequenced ) has been independently estimated at < 1 in 88,000 bases ( 23 ) . assuming a similar error rate for both 4.4 mega - bp m. tuberculosis genomes\n, we would expect to see approximately 100 differences between them due to sequencing errors .\napproximately 21 such differences would be expected in the 938,778 synonymous sites in group a and group b genes .\nin fact , 411 synonymous differences were observed at these sites ; thus , even if present , sequencing errors are likely to have made up only a small fraction ( approximately 5% ) of the total synonymous polymorphism . at such a rate ,\nsequencing errors would have little effect on our estimates of nucleotide diversity at synonymous sites or the age of the common ancestor of the two genomes .\nin addition , the hypothesis that the single nucleotide polymorphisms ( snps ) observed between these genotypes are real received strong support from a recent study that observed a number of the same snps in clinical isolates ( 24 ) . moreover , since sequencing errors are expected to occur at random with respect to the reading frame of coding sequences , the fact that mean ps exceeded mean pn in both group a and group b was strong evidence against the hypothesis that a substantial proportion of the observed polymorphism was due to sequencing error .\nsimple considerations of probability can explain why earlier studies produced relatively low estimates of this species age .\nif we assume that the per - site probability of a synonymous difference between two m. tuberculosis genomes is equal to the mean ps observed between h37rv and cdc1551 ( 0.000328 ) , then the probability is approximately 95% that no synonymous differences will be seen in a gene with 150 synonymous sites .\nthe probability that no synonymous differences will be seen in 10 such loci chosen at random is approximately 60% , and the probability that no synonymous differences will be observed at 20 such loci is approximately 37% . on the other hand , the probability that no synonymous differences will be seen at 100\nthese calculations emphasize the need to examine a very large number of nucleotide sites to obtain a reliable estimate of nucleotide diversity and thus of the age of the most recent common ancestor in cases where the frequency of substitution is less than one in a thousand .\neven when the frequency of substitution is between one in a thousand and one in a hundred , substantial stochastic error is possible if the number of loci examined is small .\nthus , any study that estimates population parameters from nucleotide sequence data needs to survey a substantial number of loci .\nthese considerations are particularly important in the case of pathogenic microorganisms , where a number of factors ( including both natural selection and horizontal gene transfer ) may lead to substantial differences among loci with respect to the level of nucleotide diversity .\ncomparison of two complete genomes of m. tuberculosis showed a greater extent of sequence polymorphism than would be expected on the basis of previous studies , in turn suggesting that analysis of additional genomes will likely show further polymorphism .\npolymorphism in any species of pathogen may complicate therapeutic strategies because it implies the existence of variation on which selection can act , including selection imposed by human vaccines and pharmacologic agents ( 20 ) .\non the other hand , known polymorphisms may prove useful to investigators in reconstructing the evolutionary relationships among clinical isolates and in providing markers for understanding the genetic basis of complex phenotypic traits .", "answer": "comparison of the pattern of synonymous nucleotide substitution between two complete genomes of mycobacterium tuberculosis at 3,298 putatively orthologous loci showed a mean percent difference per synonymous site of 0.000328 0.000022 . \n although 80.5% of loci showed no synonymous or nonsynonymous nucleotide differences , the level of polymorphism observed at other loci was greater than suggested by previous studies of a small number of loci . \n this level of nucleotide difference leads to the conservative estimate that the common ancestor of these two genotypes occurred approximately 35,000 ago , which is twice as high as some recent estimates of the time of origin of this species . \n our results suggest that a large number of loci should be examined for an accurate assessment of the level of nucleotide diversity in natural populations of pathogenic microorganisms .", "id": 9} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin dentistry , the concept of aesthetics is extremely subjective and is related to beauty , harmony and the needs of the patient .\nthe interactions between new restorative materials and techniques allow the reproduction of dental structures , restoring form and function in such a way that restorative procedures become imperceptible .\nnevertheless , during the evaluation of aesthetically compromised teeth , we encounter unfavorable clinical situations of great complexity , characterized by deep invasions of the mineralized structures .\nthe reproduction of the optical characteristics of the teeth , such as translucency , opalescence and fluorescence , requires a considerable knowledge of restorative techniques and the materials currently available .\ndental enamel defects have been associated with a broad spectrum of aetiologies , including genetic and epigenetic factors such as systemic , local and environmental factors .\na serious disturbance that occurs during the stages of enamel formation will impact the quality and/or quantity of the enamel formed , depending on the phase of amelogenesis that is affected and the duration of the stimulus on the ameloblasts .\nthe consequence of this disturbance in the formation of the organic enamel matrix is enamel hypoplasia , which can be characterized as small grooves , depressions and cracks in the enamel surface that can be viewed in mild cases .\nthis article presents a case report of a restorative treatment of enamel hypoplasia using hybrid composite resin to mask color alteration and enamel defects of the anterior upper teeth .\na 22-year - old female patient was referred to the dental clinic , reporting a visual discomfort from the presence of irregularities and discoloration in the maxillary incisors . dental history and\nclinical examination revealed that she had a soft form of enamel hypoplasia [ figure 1 ] .\nclinical examination also evidenced an enamel defect in the maxillary lateral and central incisors , with rough surfaces with irregular limits that principally involve the middle third of the crown [ figure 2 ] .\ninitial clinical aspect of the maxillary incisors a buccal view of the central and lateral incisors with hypoplastic alterations the clinical situation revealed that it was not possible to re - establish aesthetics and function without the use of a restorative procedure .\nthe position and pattern of the enamel irregularities , the occlusion and a tooth remnant with a large substrate suggested that a composite resin restoration would be a reliable option for this case .\nthe patient was systemically healthy , presented an overall plaque index and gingival index of below 10% and the restorative area was free from visible plaque .\na slight enameloplasty , using a spherical 1015f diamond bur ( kg sorensen , so paulo , brazil ) and manual instruments , was performed on both the irregularities and the limits of the tooth defect [ figures 3 and 4 ] .\nthe regularization of the defects created a good substrate that was favorable for adhesive restorations .\ndelimitation of the tooth irregularities with graphite enameloplasty with a spherical diamond bur for smoothing out defects the color was recorded using the vitapan classical scale ( vita zahnfabrik , bad sckingen , germany ) , and the shade a2/a3 was considered as the initial color .\nbriefly , the dental surface was acid etched ( 35% phosphoric acid ) [ figure 5 ] , rinsed for 30 s and dried with absorbent paper .\na two - component adhesive system ( adhese , ivoclar vivadent ag , schaan , liechtenstein ) was applied on the dentin and the enamel and was light - cured for 10 s with an intensity of 1400 mw / cm ( radii led curing light , sdi , australia ) [ figure 6 ] .\nthe dental surface was acid etched ( 35% phosphoric acid ) a two - component adhesive system was applied on the dentin and on the enamel a combination of the incremental and stratified layering technique was used to fill the tooth using a highly aesthetic nanohybrid composite resin , ips - empress ( ivoclar vivadent ag ) .\nthe composite was added in increments of 1.52 mm and was light - cured after every layer , according to the manufacturer 's instructions .\nfirst , the dentin was simulated with a thin layer of a microhybrid composite ( da3 ) and a final layer with an enamel composite ( ea2 ) , which was placed with a fine # 2 brush ( cosmedent , chicago , usa ) for fine detailing / texturizing to simulate the enamel , increasing the final brightness of the restoration [ figure 7 ] . a clinical view of the central incisor immediately after the restorative procedures\nthe contouring was refined using 30-blade carbide trimming burs ( 9714ff , kg sorensen ) , and the final polishing was performed with a high - luster polishing paste ( opal l , renfert gmbh , hilzingen , germany ) using goat - hair brushes and cotton buffs ( renfert gmbh ) .\nfour months after the restoration , a good final aspect was observed and the lateral smile view exhibited an imperceptible restoration [ figures 8 and 9 ] .\nwith the valuation of aesthetics , minimally invasive restorative techniques have provided an expansion of the current conservative philosophy .\nnevertheless , during the evaluation of aesthetically compromised teeth , we encounter adverse clinical conditions of great complexity , marked by the invasion of the mineralized structures at depth .\nenamel hypoplasia is an incomplete or defective formation in the organic matrix of the enamel and remaining certain areas susceptible to decay ; it is responsible for a major proportion of lesions .\nthe irregularities present in a hypoplasia provide favorable conditions for the retention of plaque and the early development of caries lesions , which progress and reach deep into the enamel and the dentin .\none of the signs of hypoplastic lesions is diminishing enamel luster and dental surfaces that have become eroded with cavitations and irregular wear because of the loss of the microanatomy affecting the color , morphology and texture of teeth . on some occasions , hypoplasia is mistaken for fluorosis ; however , enamel hypoplasia is an incomplete or defective formation in the organic matrix of the enamel , triggered by diseases , systemic disorders , trauma and infections in the pulp of deciduous teeth .\nit manifests with partial or complete absence of the enamel , which can be systemic ( when it affects a group of teeth ) or local ( when it has asymmetric distribution and is relegated to a single tooth ) . because it is neither fully transparent nor fully opaque ,\nsome modern composites provide optical similarities consistent with natural teeth , yielding satisfactory levels of opalescence , value and chroma .\nit is important to consider that the final restoration is dependent on both the thickness and the varying degrees of translucency and opacity of the several layers of the composite . of all dental structures\ndescribe a minimally invasive technique performed in cases of enamel hypoplasia based on enamel microabrasion and complemented with composite resin restorations .\nthe procedures employed are simple , but they require knowledge of the real causes of the staining and comprehension of restorative techniques . various treatment protocols may be performed , depending on the level of involvement and the severity of the lesions .\ncomposite resin restorations are fully capable of reproducing the appearance of a natural tooth with highly aesthetic outcomes . in this context\n, the main goal of the treatment of enamel hypoplasia is to re - establish the anatomical harmony between occlusion , function and aesthetics and to restore patient self - esteem , promoting social and psychological benefits .\nin conclusion , this case report demonstrates that restorative rehabilitation , in addition to promoting health , may provide a more favorable aesthetic appearance for the smile , matching the tooth polychromatic and raising the self - esteem of the patient .", "answer": "enamel hypoplasia is a developmental defect of the enamel that is produced by a disturbance in the formation of the organic enamel matrix , clinically visible as enamel defects . \n disorders that occur during the stages of enamel development and maturation reduce the amount or thickness of the enamel , resulting in white spots , tiny grooves , depressions and fissures in the enamel surface . \n the complexity and intensity of the dental deformity lesions will conduct the ideal treatment - associating conservative techniques . \n this article presents a case report of a restorative treatment of enamel hypoplasia using hybrid composite resin to mask color alteration and enamel defects . \n an aesthetic appearance that respects the tooth polychromatic and the self - esteem of the patient can be achieved with this approach .", "id": 10} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nadenomatoid odontogenic tumor ( aot ) is a benign , slow - growing , and noninvasive odontogenic lesion associated with an impacted tooth .\nthe presence of so - called unique duct - like structures under microscope imparts the tumor a glandular , i.e. , adenomatoid appearance .\nthe tumor is also known as two third 's tumor because about 2/3 cases occur in maxilla , about 2/3 cases are diagnosed in young females during the second decade , 2/3 cases are associated with an impacted tooth and in 2/3 cases , impacted tooth is canine .\nwe present a case of unusually large aggressive aot in the maxilla associated with impacted third molar .\na 19-year - old male reported with a chief complaint of painless mass over the left side of face and upper left back tooth region since 6 months .\ninitially , pea - sized and asymptomatic swelling appeared in upper left back tooth region .\nthree months later , swelling also appeared below left eye , initially pea - sized .\nhe gave h / o exfoliation of multiple teeth from the same region within these 6 months . on examination , solitary , smooth , roughly spherical - shaped swelling was present on the left side of face below eye .\nswelling extends from infraorbital region until malar prominence and from medial to lateral corner of left eye measuring approximately 5.0 cm 5.0 cm in maximum dimensions .\nthere was marked obliteration of palpebral fissure of the left eye [ figure 1a ] .\nintraorally , there was a solitary roughly oval - shaped growth in the left maxillary region , obliterating the buccal vestibule .\ngrowth was extending from canine region till retromolar area along alveolar ridge measuring approximately 7 cm 4 cm .\noverlying mucosa was erythematous , edematous , and inflamed . both extraorally and intraorally , swelling was firm , noncompressible , nonfluctuant , nontender , nonreducible , and nonpulsatile .\n( b ) intraoral photograph showing lesion involving palate , alveolar ridge , and buccal vestibule orthopantomogram revealed a huge , diffuse radiolucent lesion extending throughout left maxilla from canine till retromolar region . the lesion was associated with an impacted permanent upper left third molar , which was found to be present below floor of the orbit .\ncomputed tomography scan [ figure 3a c ] demonstrated a large cystic expansile radiolucent lesion with flecks of calcification of varying sizes .\nthe buccal and palatal bony expansion was remarkable , and resorption of bone with perforation was evident .\nmaxillary sinus was completely opaque . on the basis of these radiological findings , aot and pindborg tumor\northopantomogram showing a large radiolucent lesion involving left maxilla , and impacted upper left third molar teeth displaced below floor of orbit by the lesion ( red circle ) ( a - c ) computed tomography scan revealing the expansile radiolucent lesion with few radio - opaque flakes .\nthere is remarkable bony expansion and thinning and discontinuity of the palatal and buccal cortices .\nhaving accessed the tumor extraorally as well as intraorally , subtotal maxillectomy was performed , and the involved teeth were also removed [ figure 4b ] .\nthe surgical defect was simultaneously reconstructed using temporalis myofascial flap [ figure 4d ] healing was uneventful .\nsix months after surgery , computed tomogram was done which revealed complete eradication of the lesion [ figure 5a c ] .\nthere was no evidence of any recurrence 1 year after the surgery [ figure 6a and b ] .\n( a - d ) operative photographs ( a - c ) six months postoperative computed tomogram shows normal healing and no signs of recurrence ( a ) one year follow - up photograph .\n( b ) one year follow - up intraoral photograph with normal healing histological examination revealed a partially cyst - like cavity lined with the fibrous capsule . rounded and rosette - like aggregates of odontogenic epithelial cells with sparse areas of eosinophilic material could be visualized .\nthe characteristic rounded and rosette form lined with a single layer of polarised cuboidal or columnar epithelium cells giving it the adenomatoid appearance ( h and e , 400 )\naot has three clincopathological variants , namely intraosseous follicular ( 73% ) , intraosseous extrafollicular ( 24% ) , and peripheral ( 3% ) .\nthe intraosseous follicular type is associated with an impacted tooth as in our case , whereas the intraosseous extrafollicular type has no association with an impacted tooth and the peripheral variant is soft tissue component , attached to the gingival structures .\nthe lesion often leads to the expansion of the involved bone and the displacement of the adjacent teeth . owing to the slow growing and painless nature of the tumor , the patients tolerate the swelling for a long duration , sometimes years until it produces an obvious esthetic deformity .\nit may rarely show aggressive nature such as gaining unusually large size or extending into the intracranial space .\nradiographically , the lesion often demonstrates as a unilocular radiolucency associated with an impacted tooth . in certain cases , small radiopaque spots ( calcifications )\ndifferential diagnosis of aot includes dentigerous cyst , calcifying odontogenic cyst ( coc ) , calcifying odontogenic tumor ( cot ) ( pindborg tumor ) , and odontogenic keratocyst .\nradiolucency with multiple radiopaque foci ( particularly when the radiolucency surrounds a portion of the root or entire tooth ) is suggestive of an aot rather than a coc / cot .\nhistologically , aot is mostly surrounded by a well - developed fibrous connective tissue capsule .\nthe tumor is usually composed of spindle - shaped or polygonal cells forming sheets , rosettes or whorled masses in a sparse connective tissue stroma .\nthe amorphous eosinophilic material is present between the epithelial cells as well as in the center of these rosette - like structures .\nthe large size of this lesion has been attributed to a higher growth rate in younger patients and a delay in seeking treatment .\nhowever , in our case , the lesion was extremely large in size and expansile .\ntherefore , subtotal maxillectomy with simultaneous reconstruction of surgical defect with temporalis myofascial flap was planned and carried out .\nthe case presented is rare in occurrence because of certain atypical features such as unusual large size , aggressive behavior , the involvement of maxillary third molar , third molar present below floor of orbit , significant bony expansion , and cortical perforation . under general anesthesia ,\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .", "answer": "adenomatoid odontogenic tumor ( aot ) is a rare tumor comprising only 3% of all odontogenic tumors . \n it is a benign , encapsulated , noninvasive , nonaggressive , slowly growing odontogenic lesion associated with an impacted tooth . \n these lesions may go unnoticed for years . \n the usual treatment is enucleation and curettage , and the lesion does not recur . here \n , we present a rare case of an unusually large aggressive aot of maxilla associated with impacted third molar . the authors also discuss clinical , radiographic , histopathologic , and therapeutic features of the case . \n subtotal maxillectomy with simultaneous reconstruction of the surgical defect with temporalis myofascial flap was planned and carried out .", "id": 11} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSulfamate Esters Guide Selective Radical-Mediated Chlorination of Aliphatic C\\xe2\\x80\\x93H Bonds\n\nPaper sections:\n\nLate-stage alkyl C\u2013H functionalization[1] facilitates investigations into pharmaceutical small molecule leads.[2] Unfortunately, position-selective reactivity is difficult to achieve at unactivated C(sp3)\u2013H centers, which have high bond dissociation energies (90\u2013105 kcal/mol), are not acidic (pKa \u2265 50), and do not integrate more polarizable and electronically accessible \u03c0-orbitals. Consequently, in most efficient atom-transfer processes, site-selective activation originates at an electron-rich, sterically accessible bond (Scheme 1A),[1b,d,3] or is controlled kinetically by a directing group (Scheme 1B). A hydroxyl group is attractive as a directing moiety because alcohols are common within readily available small molecules. To our knowledge, there are no general strategies for aliphatic \u03b3-C\u2013H functionalization guided by a masked alcohol.[4,5] Herein described are the first experiments to demonstrate that sulfamate esters[6,7] can mediate 1,6-hydrogen-atom transfer (HAT) processes to guide the light-promoted chlorination of unactivated\u03b3-C(sp3)\u2013H centers.
Our strategy for \u03b3-functionalization is inspired by the modern resurgence of interest[8,9] in the Hofmann-L\u00f6ffler-Freytag (HLF)[10\u201312] reaction. In traditional HLF processes, position selectivity arises based on formation of an intermediate nitrogen-centered radical that engages in a 1,5-HAT process[13] through a kinetically favored, six-membered transition state.[14] By contrast, we anticipate sulfamate esters may be capable of mediating 1,6-HAT processes, which are rare[15] as they are expected to proceed through seven-membered transition states, which are often kinetically disfavored.[16] We hypothesize that sulfamate esters enable 1,6-HAT because their elongated O\u2013S and S\u2013N bonds (\u223c1.58 \u00c5) and compressed O\u2013S\u2013N bond angles (\u223c103\u00b0)[17] geometrically favor a seven-membered ring transition state for C\u2013H abstraction. The site-selectivity available through these reactions complements that achieved using traditional HLF chlorination transformations,[18] alternative guided chlorination methods,[19] or site-selective intermolecular[20] chlorination processes.
This approach is demonstrated in the course of site-selective chlorine-transfer to convert N-chlorinated sulfamate esters 1 to alkyl chlorides 2 (Scheme 1B). Predictable control has proven more challenging in C(sp3)\u2013H chlorination[21] than bromination reactions,[12d,22,23] owing to the promiscuity of chlorine radical promoted hydrogen-atom abstraction. Nevertheless, alkyl chlorides are useful synthetic intermediates, and components of bioactive small molecules, with >2000 known chlorine-containing natural products.[24] Consequently, new technologies for selective aliphatic C\u2013H chlorination have potential to streamline syntheses of bioactive small molecules.[25]
To minimize mechanistic uncertainty, we chose to generate nitrogen-centered radicals by using light to homolyze nitrogen\u2013chlorine bonds of N-chlorosulfamate esters 1. N-chlorosulfamate esters 1 are readily available from sulfamate esters 3[26] upon treatment with trichloroisocyanuric acid or tert-butyl hypochlorite (see supporting information for details).As anticipated, photolysis of pentyl methylchlorosulfamate ester 1a results in selective \u03b3-chlorination at a methylene center (Table 1, entry 1, C\u2013H bond dissociation energy (BDE) \u223c 98 kcal mol\u20131).[27] This reaction does not occur in the absence of light, indicating that photolysis initiates the reaction.
Chlorine-transfer proceeds from N-methyl-, N-tert-butyl-, N-trifluoroethyl- and N-2-(pyridin-2-yl)isopropylchlorosulfamate esters 1a\u2013d (Table 1, entries 1\u20137). The corresponding series of sulfamate esters 3 are predicted to differ in terms of N\u2013H bond acidity[28] by more than three pKa units, indicating that the reaction tolerates broad electronic variations across N-alkyl substituents. In all of these cases, the remaining mass balance can be accounted for principally by reduced 3. Notably, in the reaction of substrate 1b, <2% yield of \u03b4-chlorinated product 4b (not depicted) can be detected in the crude reaction mixture along with desired \u03b3-chlorinated 2b.While N-alkylsulfamate esters facilitate chlorination, some N-arylsulfamate esters may not engage in productive guided chlorine-transfer processes, as photochemical irradiation of arylated 1e generates a complex mixture of products.
In these chlorine-transfer processes, site-selectivity is orthogonal to that available through most atom-transfer processes reliant on innate selectivity. In the productive transformations of N-chlorinated 1a\u2013d, chlorinated alkanes 2a\u2013d are formed with exquisite \u03b3-selectivity, despite the fact that \u03b4-functionalization is expected to be favored under conditions that rely on inherent selectivity (Table 1; Scheme 1A).
Guided selectivity is preserved across a range of O-alkyl sulfamate esters (Table 2). For menthol-derived 1f, C(5)\u2013H and C(8)\u2013H bonds are expected to have very similar electron densities.[29] Nevertheless, unguided tertiary-selective intermolecular oxidation[29] and amination[30] processes result in selective functionalization of analogues at C(5), presumably because the C(8)\u2013H bond is sterically encumbered.[29] By contrast, under the described conditions, chlorination occurs exclusively at C(8)\u2013H, which is poised to interact with the sulfamate ester nitrogen-centered radical (entry 1) via a seven-membered transition state. This position-selectivity is analogous to that displayed in iron- and manganese-nitrene-mediated intramolecular amination reactions of sulfamate esters.[31,32]
Furthermore, the directed chlorination reaction overcomes the innate site-selectivity that arises from inductive deactivation in unguided oxidation processes. In unguided C\u2013H functionalization reactions, proximity to inductively electron-withdrawing groups deactivates C\u2013H bonds to oxidation. This phenomenon is evident when 3,7-dimethyloctanol is masked with an electron withdrawing group, and engages in undirected fluorination,[33] oxygenation,[34] amination,[35] azidation,[36] or trifluoromethylthiolation[37] processes that functionalize C(7) in preference to C(3). By contrast, the sulfamate ester-guided chlorination installs chlorine at the electronically deactivated C(3) position (entries 2\u20133).
Moreover, this guided functionalization process overcomes selectivity that typically arises from differences in bond strength. Pendant silyl ether 1i undergoes efficient and selective \u03b3-chlorination, without oxidation of the weak etherial C\u2013H bonds (BDE \u223c 85 kcal mol\u22121, entry 4).[27]
In addition to differentially masked diols, the reaction conditions are compatible with a variety of functional groups. Sulfamate esters derived from N-protected amino alcohols engage in selective atom-transfer, as phthalimidyl 1j provides chlorinated 2j in 82% isolated yield (entry 5). As noted previously, the reaction also allows pendant heteroaromatic moieties (Table 1, entry 7) and fluorides (Table 1, entries 4\u20136; Table 2, entries 1, 3\u20135, 9).
This method transforms C(sp3)\u2013H bonds at secondary, tertiary (BDE \u223c 96 kcal mol\u20131),[27] and benzyliccenters (BDE \u223c 90 kcal mol\u20131)[27] in synthetically useful yields (entries 1\u20138). Generally, chlorination of \u03b3-C(sp3)\u2013H centers occurs in preference to \u03b2-C\u2013H centers, even when the \u03b3-C\u2013H bond is primary and significantly stronger (BDE \u223c 101 kcal mol\u22121)[27] than a secondary \u03b2-C\u2013H bond. For example, chlorination of propyl tert-butylsulfamate ester 1m and (\u2013)-borneol derivative 1n occur at the stronger primary C\u2013H bonds, albeit with diminished efficiency (entries 8\u20139). While each of these substrates displays a geometrically accessible \u03b2-methylene center, chlorination at these positions is not detected. Instead, dehalogenated sulfamate esters 3m and 3n are the primary by products of these transformations. An analogous reactivity trend has been documented with White's manganese-catalyzed intramolecularamination with sulfamate esters.[32]
In principle, this chlorination reaction could proceed through a closed cycle and/or a radical chain propagation mechanism (Scheme 2). In either pathway, initiation would occur by light-promoted N\u2013Cl bond homolysis, thereby converting N-chlorosulfamate ester 1b to chlorine radical and sulfamyl radical 5b. The resulting nitrogen-centered radical 5b mediates an intramolecular 1,6-HAT to generate a carbon-centered radical 6b with exquisite position selectivity. Subsequent divergence in carbon\u2013chlorine bond forming events then distinguishes between the proposed pathways. In the closed radical cycle mechanism, intermediate carbon-centered radical 6b recombines with the chlorine radical to terminate the reaction and provide 2b (not depicted). Alternatively, carbon-centered radical 6b could engage in chlorine-atom abstraction with another equivalent of N-chlorosulfamate ester 1b (Scheme 2). This sequence would release desired halogenated 2b, along with another equivalent of radicalloid 5b, which could propagate this chain reaction.
These mechanistic hypotheses differ in terms of the number of product equivalents that can be generated per absorbed photon, a relationship that defines quantum yield (\u03a6). While a closed radical cycle could furnish a maximum of one product molecule per absorbed photon (\u03a6 \u2264 1), a radical chain propagation mechanism could provide multiple equivalents of the product per absorbed photon (\u03a6 > 1).
Quantum yield measurements have been performed to provide insight into the operative reaction mechanism,[38] and provide evidence that the reaction proceeds through a light-initiated chain propagation mechanism. Briefly, standard chemical actinometry using potassium ferrioxalate allowed us to determine the photon flux of a fluorimeter at 313 nm.[38,39] After 15 minutes of irradiation of N-chlorinated 1b in benzene at 313 nm in the calibrated fluorimeter, 68% conversion to chloroalkane 2b is observed. This yield corresponds to 77 equivalents of product formed per absorbed photon (\u03a6 = 77), indicating that this reaction proceeds through a chain propagation mechanism.
This sulfamate ester-guided HLF reaction is expected to provide a powerful and general platform to complement current HLF technologies. This research is among the first to establish that sulfamate esters can mediate 1,6-HAT such that the generated carbon-centered radicals can be trapped efficiently in guided intermolecular reactions. Furthermore, the method provides efficient access to secondary and tertiary alkyl chlorides, a valuable class of synthetic intermediates, with novel and predictable site-selectivity.
", "answer": "Masked alcohols are particularly appealing as directing groups because of the ubiquity of hydroxyl groups in organic small molecules. Herein, we disclose a general strategy for aliphatic \\xce\\xb3-C(sp3)\\xe2\\x80\\x93H functionalization guided by a masked alcohol. Specifically, we determine that sulfamate ester-derived nitrogen-centered radicals mediate 1,6-hydrogen-atom transfer (HAT) processes to guide \\xce\\xb3-C(sp3)\\xe2\\x80\\x93H chlorination. This reaction proceeds through a light-initiated radical chain-propagation process and is capable of installing chlorine atoms at primary, secondary, and tertiary centers.", "id": 12} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nTwo-photon uncaging of \\xce\\xb3-aminobutyric acid in intact brain tissue\n\nPaper sections:\n\nTwo-photon (2P) excitation is a method that has revolutionized many areas of biological science as it enables three-dimensionally defined excitation of chromophores in biological tissue1,2. We previously developed 4-methoxy-7-nitroindolinyl-L-glutamate (MNI-Glu3\n1) and 4-carboxymethoxy-5,7-dinitroindolinyl-L-glutamate (CDNI-Glu4\n2) for 2P uncaging in mammalian brain slices. Depending on the size of the 2P excitation volume, we mimicked synaptic quantal release of glutamate using diffraction limited 2P uncaging3 or fired action potentials and mapped unitary synaptic connections in a large volume of the neocortex using macro 2P uncaging5. Although a variety of caged glutamate probes have been reported6, \u03b3-aminobutyric acid (GABA), has received comparatively little attention from chemical biologists, and 2P uncaging of this vital neurotransmitter has not been reported. We have synthesized a new caged GABA derivative (CDNI-GABA, 3) that undergoes 2P photolysis in living brain slices with low power (ca. 10 mW at 720 nm) and at low concentrations (0.40-1.35 mM). Two-photon uncaging of CDNI-GABA over the axon initial segment (AIS) of CA1 pyramidal neurons enabled high resolution functional mapping that showed a punctate distribution of GABA-A receptors. Successive functional mapping of the apical dendrite with CDNI-GABA and MNI-Glu revealed no correlation between the distribution of GABA and glutamate receptors. CDNI-GABA uncages rapidly and efficiently (quantum yield of 0.60), therefore this new caged GABA probe is a useful addition to the optical toolbox available to neuroscientists.
The synthesis of CDNI-GABA (Fig. 1a) is outlined in Supplementary Fig 1. The quantum yield for uncaging of CDNI-GABA was determined by comparison with a known photochemical standard. HPLC analysis of the time-course of photolysis showed that CDNI-GABA was photolyzed about seven times faster than MNI-Glu, implying that the quantum yield of photolysis was 0.60 (\u00b1 0.02, n=3). The presence of a strongly electron withdrawing group at the 5-position promotes deprotonation of the C-2 hydrogen, enhancing the quantum yield of bond scission to give the desired uncaged amino acid.
Photolysis of CDNI-GABA near the edge of the perisomatic apical dendrite of CA1 pyramidal neurons (Fig. 1b) with 6.3 mW for 1 ms evoked fast inhibitory postsynaptic potential currents (which we call \"2pIPSCs\", see Fig. 1c) that were blocked by picrotoxin (PTX 4, Fig. 1d). Because power requirements for 2P uncaging of CDNI-GABA were low, we reasoned that this new caged GABA could enable three-dimensional mapping of receptor densities3, without fear of photodamage. Functional mapping at four z-sections (Fig. 1e) revealed that the axial resolution of the evoked current was close to the diffraction limit (Fig. 1f; full-width at half-maximum (FWHM) = 2.1 \u03bcm, microscope resolution 1.4 \u03bcm at 720 nm). These data show that non-linear excitation particularly helps limit axial uncaging in comparison to UV-visible (i.e. 1P) excitation. Similar benefits have been reported for 2P uncaging of glutamate in brain slices7-10.
We established that the evoked currents arose from 2P excitation1 by mapping the GABA-A receptor density across the surface of the apical dendrite with and without laser mode-lock (Fig. 1g-i). No current was evoked with a mode-unlocked laser (Fig. 1h), whereas similar functional receptor maps were detected before and after this experiment with a mode-locked laser (Fig. 1g,i).
Two-photon uncaging of CDNI-GABA allowed us to approximate miniature IPSCs (mIPSCs), as the rise time and decay kinetics of 2pIPSCs were similar to those of spontaneous mIPSCs (Fig. 1j, and Supplementary Table). Specifically, the average rise time (20-80%) of the 2pIPSCs was 2.0 \u00b1 0.2 ms (6-112 events per cell, n = 6 cells), whereas the average rise time of the spontaneous mIPSCs was 1.5 \u00b1 0.2 ms (10-66 events per cell, n = 6 cells). The average rise times of the 2pIPSCs and mIPSCs were not significantly different (P = 0.075, paired t test). The decay half-times were 24.7 \u00b1 2.5 ms (2pIPSCs) and 10.5 \u00b1 1.1 ms (mIPSCs), which were significantly different (P < 0.005, paired t test, n = 6 cells). Since 2P uncaging of CDNI-GABA on the perisomatic dendritic membrane showed a dense distribution of GABA-A receptors (Fig. 1e), the longer decay time of the 2pIPSC probably reflects the increased clearance time of uncaged GABA from clusters of GABA-A receptors near the focal volume of 2P excitation.
Funtional mapping with CDNI-GABA was reproducible (Fig. 1g,i correlation coefficient (CC) of 0.65 \u00b1 0.02, n = 4 pairs of maps in 4 cells), implying that hot spots of GABA responses do not rapidly diffuse laterally. If such hot spots were GABAergic synapses, they should be devoid of glutamate receptors, because GABAergic and glutamatergic synapses are structurally different11. Comparison of functional maps of GABA-A and \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors on the same proximal dendrites (Fig. 2a,b) showed CC of 0.22. These data suggest that the hot spots of functional GABA-A receptors were anchored clusters of GABA-A receptors, probably GABAergic postsynaptic sites, and that the number of functional GABA-A receptors varied among synapses.
One of the major functions of GABA-A receptors is to modulate the generation of action potential in the AIS where sodium channels are densely distributed12. Although immunological staining has revealed that axo-axonic cells innervate the AIS via GABAergic synapses with GABA receptors13,14, the functional distribution of GABA-A receptors along the AIS has not been clarified. Thus, we performed three dimensional mapping of GABA-A receptors on the AIS. We detected heterogeneous responses of functional GABA-A receptors along the AIS over 40 \u03bcm (Fig. 2c,d). The kinetics of the currents (Fig. 2e) was similar to that obtained at the somatic membrane. The detection of functional GABA-A receptors on the AIS needed a higher energy of 2P excitation than that used at the perisomatic apical dendrite. Immunoelectron microscopy has shown that synaptic size and the number of synaptic GABA-A receptors in the AIS are smaller than those in the soma14. Our data confirm this, showing a functionally disparate distribution of inhibitory receptors at the major input and output pathways of pyramidal neurons.
The most widely used15 caged GABA (\u03b1-carboxy-o-nitrobenyl[CNB]-GABA16\n5) has been reported to be a mild antagonist of GABA-A receptors17. Consequently we tested the basic pharmacology of CDNI-GABA, the structurally related CNI-GABA 6 and the widely used MNI-Glu. Concentrations of 0.325 mM CNI-GABA when bath-applied in the artificial cerebrospinal fluid (aCSF) perfusate have no effect on the tonic firing of neurons of the deep cerebellar nuclei in brain slices18. We found that a much higher concentration of CNI-GABA (10 mM), which we used for 2P uncaging (data not shown), or CDNI-GABA (10 mM) inhibited GABA-A receptors currents in acute hippocampal slices when co-applied with GABA itself (Supplementary Fig. 2a and 2b). Much to our surprise the same concentration of MNI-Glu (as used in Fig. 2) had similar effects (Supplementary Fig. 2b). These findings implied that high concentrations of structurally diverse caged transmitters such as MNI-Glu, CNI-GABA, and CDNI-GABA block GABA-A receptors. In particular, the block of GABA-A receptors by MNI-Glu indicates a potential risk for caged neurotransmitters to affect receptors other than their intended target. The lower concentration of CDNI-GABA (1.35 mM) used for Fig. 1 and Fig. 2 still reduced GABA-A receptors current when co-applied with 0.1 mM GABA by 70 % (Supplementary Fig. 2a and 2b). Spontaneous mIPSCs were surpressed during puff application of 1.35 mM CDNI-GABA (Supplementary Fig. 2c.) However, 0.4 mM CDNI-GABA reduced currents by only 22 % (Supplementary Fig. 2b). Further, the antagonism on the size and frequency of spontaneous mIPSCs at 0.4 mM was mild, as almost immediately after the end of the puff the standard-sized signals of spontaneous mIPSCs reappeared (Supplementary Fig. 2d). We tested 2P uncaging at this concentration and found it was feasible (Supplementary Fig. 3). Thus CDNI-GABA can be used for 2P functional mapping under conditions of very mild antagonism towards GABA-A receptors.
A variety of caged GABA compounds have been reported over the past 14 years16,18-21. However, only CNB-GABA16 has been used by many laboratories15, and so the properties of this important compound are compared with CDNI-GABA, along with recent alternative approaches18-20, in Table 1. CDNI-GABA is not only uniquely effective for 2P functional mapping (Figs. 1,2), it is significantly more photochemically efficient for UV-visible photolysis (i.e. \u03b5.\u03c6 ) than the other caged GABAs (Table 1).
The inherent non-linear nature of 2P microscopy means that axial excitation is greatly restricted when compared with UV-visible excitation1,2. This property has enabled several laboratories to achieve stimulation of AMPA receptors on isolated spine heads3,4,7-10,22-25 using 2P uncaging of glutamate. In this report we introduce a new caged compound, CDNI-GABA, that releases GABA with high quantum efficiency (0.6) and that undergoes effective 2P photolysis. Two-photon uncaging of CDNI-GABA on neurons in brain slices evoked rapid postsynaptic currents with an axial resolution of about 2 \u03bcm. This accuracy allowed high-resolution functional mapping of GABA-A receptors along the axon initial segment and the perisomatic dendritic region of CA1 pyramidal cells for the first time. Two-photon photolysis of CDNI-GABA should be a powerul tool to clarify, for example, GABAergic inhibitory effects on the ion flux through excitatory synapses, the propagation of depolarization along dendrites, and the generation of action potentials at the micrometer and even single synaptic level.
", "answer": "We have synthesized a photosensitive (or caged) 4-carboxymethoxy-5,7-dinitroindolinyl (CDNI) derivative of \\xce\\xb3-aminobutyric acid (GABA). Two-photon excitation of CDNI-GABA produced rapid activation of GABAergic currents in neurons in brain slices with an axial resolution of approximately 2 micrometers, and enabled high-resolution functional mapping of GABA-A receptors. Two-photon uncaging of GABA, the major inhibitory neurotransmitter, should allow detailed studies of receptor function and synaptic integration with subcellular precision.", "id": 13} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto report a case of recurrent idiopathic frosted branch angiitis ( fba ) successfully treated with adalimumab .\na 14-year - old otherwise healthy boy was referred to the uveitis clinic for bilateral panuveitis with diffuse retinal vascular sheathing and severe macular edema .\ntwo years ago , a similar episode had been treated with oral prednisolone , however it was complicated by adverse psychiatric effects .\nthe progressive course of the condition mandated considering other therapeutic measures ; adalimumab was chosen based on its purported efficacy for treatment of childhood uveitis and a favorable safety profile .\nthe patient responded dramatically to a single subcutaneous injection of adalimumab without any side effect during and after injection .\nto the best of our knowledge , this is the first case of idiopathic fba treated successfully with adalimumab without adjunctive steroid therapy .\nfrosted branch angiitis ( fba ) is a rare disease characterised by visual disturbance associated with anterior chamber and vitreous inflammation and severe sheathing of retinal vessels resembling the appearance of frosted branches of a tree .\nit was originally described in a six - year - old child by ito in 1976.1 fba can be associated with ocular and systemic diseases .\ncytomegalovirus retinitis , acquired immunodeficiency syndrome , and toxoplasma chorioretinitis are frequent ocular associations , while systemic lupus erythematosus , crohn 's disease , behcet s disease , large cell lymphoma , and acute lymphoblastic leukemia have been described as systemic associations.2 the idiopathic type typically occurs in young and healthy persons and is associated with good recovery of vision .\na 14-year - old boy , who was otherwise healthy , was referred to the uveitis clinic for progressive blurring of vision in both eyes since 1 month before . on examination ,\nanterior segment examination revealed mild ciliary injection and anterior chamber reaction ( 2 + cells ) but no keratic precipitates or posterior synechiae .\nboth eyes had inflammatory reaction in the vitreous ( 2 + cells ) but there were no snow balls or snow bank formation .\nfundus examination disclosed extensive retinal vascular sheathing and scattered intraretinal hemorrhages with severe macular edema in both eyes ( fig .\n1 ) . systemic work - up and investigations , including a complete blood count ( cbc ) , erythrocyte sedimentation rate ( esr ) , c - reactive protein ( crp ) titer , angiotensin converting enzyme ( ace )\ntiter , tuberculin skin test ( tst ) , urine analysis and chest x - ray were unremarkable .\nrheumatologic tests including antinuclear antibodies ( ana ) , anti double strand dna antibody ( anti ds - dna ) , rheumatic factor ( rf ) , antiphospholipid antibody , anti - neutrophil cytoplasmic antibodies ( ancas ) , and cryoglobulin assay were all negative .\nblood cd4 and cd8 counts were within normal range and serology for the human immunodeficiency virus was also negative .\nblood serology for possible infectious causes including herpes family viruses , i.e. herpes simplex virus ( hsv ) type 1 and 2 , varicella zoster virus ( vzv ) , cytomegalovirus ( cmv ) , and epstein - barr virus ( ebv ) , hepatitis b and c viruses , treponema , borrelia , and toxoplasma were checked .\nimmunoglobulin g ( igg ) levels against hsv type 2 and cmv ( but not igm ) were elevated .\nwe tested the aqueous specimen after an anterior chamber paracentesis to investigate the presence of deoxyribonucleic acid ( dna ) of hsv type 1 and cmv viruses .\nthe result of polymerase chain reaction ( pcr ) on aqueous samples was negative for both viruses . until the results of blood tests and aqueous pcr became ready , vision continued to deteriorate down to 20/1000 and 20/800 in the right and left eyes , respectively . based on the inconclusive work - up a diagnosis of idiopathic fba\nthe patient s parents mentioned that two years ago , for treatment of a similar condition , oral prednisolone 1 mg / kg had been commenced but soon after initiation , the patient developed severe mood changes which persisted long after discontinuation of treatment .\nthe progressive nature of the condition mandated considering other therapeutic measures to prevent macular scarring . due to the safety profile of anti - tumor necrosis factor ( tnf ) agents and their rapid onset of effect ,\nadalimumab was considered as an alternative to conventional treatment for which the parents provided written informed consent .\na single dose of 40 mg pre - filled adalimumab ( humira , abbott laboratories , north chicago , il , usa ) was injected subcutaneously in the patient s right thigh .\nno local or systemic adverse effect was noted at the time of injection or later on .\nthree weeks after injection , visual acuity improved to 20/200 and 20/120 in the right and left eyes , respectively .\nanterior chamber and vitreous reaction decreased to 1 + cell , and vascular sheathing and macular edema resolved dramatically .\nrepeat fluorescein angiography and optical coherence tomography ( oct ) confirmed the improvement ( figs . 2 and 3 ) .\n10 weeks after injection , visual acuity improved to 20/40 and 20/30 in the right and left eyes , respectively . in both eyes ,\nclinical improvement continued up to the last visit ( 6 months after the injection ) when visual acuity reached 20/25 in both eyes with no sign of active inflammation .\nfba is basically divided into three different subgroups.3 the first comprises patients affected by lymphoma and leukemia presenting with a frosted branch - like appearance in the fundus .\nthe second group includes patients with associated autoimmune or viral disease which can present with fba in association with the underlying disease .\nthe characteristic feature of this latter type is its occurrence in otherwise healthy young individuals with good recovery of vision .\nclinically , there is severe sheathing of retinal vessels appearing like the frosted branches of a tree , and acute visual disturbance associated with anterior chamber and vitreous inflammation ; fluorescein angiography shows leakage from sheathed vessels without signs of occlusion or stasis.4,5 systemic steroids are the main and only suggested treatment for this condition . in our patient however , prior adverse psychiatric effects of steroid treatment encouraged us to employ another therapeutic option : adalimumab , a fully humanized monoclonal anti - tnf antibody , was chosen based on its suggested effect for treatment of refractory childhood uveitis including juvenile idiopathic arthritis.6 - 8 our patient responded dramatically to a single subcutaneous injection of adalimumab .\nthe improvement was rapid and long lasting and the patient did not report any side effect during follow up .\nreview of the literature revealed no other therapeutic option for treatment of idiopathic fba except systemic steroids . to our best knowledge\n, this is the first case of idiopathic fba treated successfully with an anti - tnf agent without adjunctive steroid therapy .", "answer": "purposeto report a case of recurrent idiopathic frosted branch angiitis ( fba ) successfully treated with adalimumab.case reporta 14-year - old otherwise healthy boy was referred to the uveitis clinic for bilateral panuveitis with diffuse retinal vascular sheathing and severe macular edema . \n extensive work - up including aqueous sampling for detection of viral causes was inconclusive . \n two years ago , a similar episode had been treated with oral prednisolone , however it was complicated by adverse psychiatric effects . \n the progressive course of the condition mandated considering other therapeutic measures ; adalimumab was chosen based on its purported efficacy for treatment of childhood uveitis and a favorable safety profile . \n the patient responded dramatically to a single subcutaneous injection of adalimumab without any side effect during and after injection . \n the therapeutic effect was rapid and relatively long-lasting.conclusionto the best of our knowledge , this is the first case of idiopathic fba treated successfully with adalimumab without adjunctive steroid therapy .", "id": 14} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe introduction of digital technologies in clinical pathology practice could produce great benefits in the form of improved patient care , better efficiency of health services , and novel diagnostic tools . at the same time\n, it is clear that these benefits can only be achieved if digital pathology solutions are carefully crafted for the clinical prerequisites . whereas low - volume and nonurgent situations such as research , teaching , and to some extent , consultations , are currently feasible with existing digital pathology systems , if digital pathology is to reach prime time status then more work is needed to enhance the suitability of the systems for clinical routine .\nclinical deployment also requires solving issues such as validation mechanisms , cost - efficient digital storage , and medico - legal demands , as well as redesigning work practices for the digital era .\nefforts to advance the field are taking place around the world . in the nordic countries ( sweden , denmark , norway , finland , and iceland ) , there is a particular concentration of development work towards clinical use of whole slide imaging ( wsi ) . for example , all routine histology slides are today scanned in the hospitals of linkping and kalmar and extensive digital primary review is performed , and > 60 wsi scanners have been installed in sweden to date . against this backdrop , the nordic symposium on digital pathology ( ndp ) was created to promote knowledge exchange regarding the state - of - the - art in digital pathology .\nthe specific focus of ndp is advances toward the clinical adoption of wsi and other digital technologies in pathology .\nas these advances require a concerted effort from health care , industry , and academia , ndp is intended as a forum where professionals from all domains can meet .\nthe first ndp event was organized in november 2013 and attracted 125 attendees , whose feedback lead to an expanded ndp event in november 2014 as will be detailed below .\njudging from the history of digitization of radiology imaging , there is reason to believe that the nordics will continue to be a forerunner in clinical use of digital pathology .\nwhile perhaps not reflected by its regional name , ndp aims to be a venue of broad international interest where state - of - the - art in digital pathology is discussed and advanced .\nnordic symposium on digital pathology symposium 2014 took place november 56 in linkping , sweden .\na total of 144 attendees gathered , of which 47% listed health care as the primary affiliation , 33% industry , and 19% academia .\nthe health care representatives were dominated by pathologists , but also laboratory technologists and it staff were in significant numbers .\nthe participants represented 14 different countries from europe , north america , and australia , with the nordic attendees being in a large majority ( 87% ) .\ncentral to the program was a series of invited talks and a collaborative workshop on clinical deployment issues .\nthe contents of these sessions will be outlined in the sections below . in the science and innovation session ,\na double - blind review process was carried out by the symposium 's international program committee with 15 senior researchers in the field and this resulted in three jpi papers published alongside this editorial : a comparative study of input devices for digital slide navigation ( jesper molin et al . ) , randomspot : a web - based tool for systematic random sampling of virtual slides ( alexander wright et al . ) , and histopathology in three - dimensional : from three - dimensional reconstruction to multi - stain and multi - modal analysis \nin addition , the ndp included an industrial exhibition consisting 13 vendors , ranging from large multinationals to recent startups , showing everything from wsi scanners through enterprise image management to desktop electron microscopy .\nfigure 1 shows a session snapshot and the program details are available at the npd website http://www.liu.se/ndp?l=en .\na key part of the ndp program was the workshop discussing clinical adoption of digital pathology .\nthe workshop was organized as an open floor discussion where broad participation was encouraged and also achieved . as an input to the discussion\n, a survey was distributed among the health care attendees in advance of the symposium .\nsome results from this survey will be presented next as it paints an interesting picture of the attitude toward digital pathology in nordic health care .\nit must be noted that the respondents of the survey represents an extremely biased selection among the pathology community .\nsince only ndp participants were asked , this means that respondents are likely to be among the most positive to digital pathology and also among the most experienced .\nthere is also strong geographical dominance from the nordics and in particular sweden . of 74\nit is likely that the pathologist dominance were even higher for some questions that require deep knowledge of clinical practice .\nrole distribution of survey respondents the survey first asked : today , to what degree do you use digital images of histology slides in your practice ? ( in % of all histology cases . ) the results are shown in figure 3 , showing moderate levels of adoption but no use in about 50% of respondents .\nanother bias to note for these questions is that several people from the same institution may have responded . since the most digitized sites kalmar and linkping had several attendees , these numbers are likely to represent higher usage than numbers on a per site basis .\ncurrent use of digital pathology among survey respondents the same question was asked for the predicted situation at the end of 2016 , shown in figure 4 , showing significant optimism for near - future use of digital pathology . predicted use of digital pathology at the end of 2016 the respondents\nwere also asked to judge the impact of digitization : what effect do you foresee that digital pathology will have compared to traditional microscope practice , with regards to the following areas ? the impact grading was given in a five - point scale , \nmajor negativeminor negative status quo minor positive major positive . \nthe assessments with regards to pathologist work are in figure 5 whereas other laboratory aspects are in figure 6 and overall impact in figure 7 . foreseen impact of digitization with regards to pathologist 's work foreseen impact of digitization with regards to laboratory aspects foreseen impact of digitization with regards to overall effects broadly , these responses indicate a very positive attitude toward digital pathology in terms of its effects on pathologist and laboratory working .\nhowever , more negative responses were received in the effect on pathologists efficiency ( time per case and speed of slide navigation ) as well as perceived delays in slide arrival from the laboratory until starting review .\noverall effects of digitization were seen as very positive , especially for the quality of care .\nfinally , the respondents also were asked to state the three main barriers for adoption of digital pathology in their clinical practice .\nit was clear that the cost of implementation is a major issue ; 79% of the responses mentioned lack of sufficient funds as a barrier .\ntechnology limitations were listed in 71% of the responses , some referring to insufficient performance of commercial solutions and some referring to lacking it infrastructure in their organization . a conservative attitude among colleagues\nother responses concerned lack of organizational engagement at local , national and international levels to develop protocols , work practices , and standards .\nafter the survey results had been presented , a guided discussion between all participants took place .\nadvanced digital pathology implementation efforts were reported by many contributors , either established ( e.g. skne , linkping ) or in planning ( e.g. , gothenburg , karolinska / stockholm , oslo , copenhagen ) .\nthe planned use cases covered similar areas such as retrieving archived cases , presenting at multi - disciplinary meetings , obtaining second opinions ( either for individual cases or to share work between institutions ) .\ndigital pathology was seen by many contributors as a key enabler of higher quality pathology services , by increasing specialist reporting of cases or supporting and supporting colleagues across distances .\nthose who had implemented digital pathology on a large scale were positive about the effects it had on workflow and reported no untoward delay in slide arrival caused by the extra step of scanning ( in fact , one pointed out that the cases arrived in a more continuous flow , rather than the batches of glass slides normally received ) .\nseveral contributors ( linkping , skne , toronto ) had experience of working with moderate or large volumes of the digital work .\nfatigue using dp systems was mentioned by a few , possibly a combination of older less effective slide viewing software and the known effect of computer displays on eye fatigue .\nseveral experienced commenters pointed out that fatigue was often an issue with the microscope and that digital pathology offered ergonomic benefits which could be beneficial in the long term for the pathologist 's experience .\nlaboratories produce a lot of glass slides , and wsis produce large amounts of storage space .\nit was felt that data storage was very often raised as a concern by it departments involved in discussions about digital pathology implementations .\nsome contributors pointed out that projections of hundreds of terabytes of image data per year , while realistic for 100% digital practice , may serve to inhibit pathologists and it departments from trying the technology , and that in fact to start going digital - only a modest storage capacity of a few terabytes is needed .\nit contributors pointed out that mature information lifecycle management systems for digital pathology had yet to appear ( some contributors reported being charged excessive monthly costs for even small amounts of data ) , but it was likely that tiered storage systems would ameliorate the daunting costs associated with large amounts of live online storage , as would the constant reduction in price per terabyte of storage media .\nsome discussion around how long digital images should be kept for and what latency before image retrieval might be tolerated revealed that several contributors had envisaged such tiered data arrangements would be needed .\ncenters with mature or second - generation digital pathology systems often had it staff who understood well the complexities of wsi data , and well - integrated systems .\nexperienced users re - emphasized the need for digital pathology to be supported by knowledgeable and ( preferably ) designated it staff .\nstandards were mentioned by only a few contributors - the it staff , who expressed surprise at the lack of standardization of digital pathology image formats and interoperability , and those pathologists on their second generation of scanners who had experienced incompatibility between two different vendors products ( e.g. in viewers or in image analysis algorithms ) .\nsome audience members had experience of the last digital revolution in medical imaging ( in radiology ) and saw many parallels in the it needs , questions about validation / safety and clinical acceptance of the technology .\nthe room was understandably full of those keen to adopt digital pathology , many of whom reported colleagues with more conservative attitudes .\nsome of the objections were seen , however , as entirely justifiable ( e.g. concerns over speed of diagnosis and diagnostic accuracy with digital systems ) and many in the room agreed that these were issues that needed to be addressed . for successful implementations ,\nthe need for champions in each department was mentioned , as well as the value in immersing trainees in a digital working pattern from an early stage .\nwiser ( and older ) heads pointed out the benefits of actively seeking out sceptics and involving them in digitization projects .\ndr . andrew evans from the university health network , toronto described a long - standing program of digitization including telepathology and wsi in a university hospital network .\nhe provided a very detailed description of the assiduous planning involved in digital pathology adoption and his experiences of involving the entire department in projects .\nmetin gurcan of ohio state university spoke about his work in image analysis and computer aided diagnosis , introducing many parallels from radiological imaging and emphasizing the importance of pathologist - computer scientist partnerships and validation in such work .\njan baak from stavanger university hospital gave an expansive talk on his long career in pathology imaging , especially speaking about his role in the prognostication of breast cancer with morphology and image analysis , emphasizing the ongoing value of good pathological assessment even in a genomic era .\ndr . sten thorstenson from linkping university hospital explained his long experience of digital pathology at kalmar and linkping , starting at a time when a terabyte really was a large amount of data .\nafter 9 years he reports being entirely comfortable working digitally and has been reporting 100% from home for almost a year now without access to a microscope or physical slides .\nderek magee from the university of leeds gave an overview of his work in image analysis research .\na focus area has been digital three - dimensional pathology , and in particular tackling the inherent challenges of the slide registration , color normalization , and histology - radiology correlation .\nthomas miliander from vrmland county council , sweden , presented this health - care provider 's strategy for imaging it infrastructure .\nthe approach taken is an enterprise image management backbone for all medical images , relying on standards for tight integrations with other information systems , a context into which now also wsi is entering .\njohan lundin from the institute for molecular medicine finland , helsinki , provided an overview of his group 's work in digital pathology .\nthe portfolio presented spanned from web and touch - enabled wsi viewing applications to low - cost handheld microscopes utilizing smartphone camera components . in a special session ,\nelin kindberg of sectra presented preliminary results from a national swedish effort to investigate key medico - legal issues arising when deploying digital pathology . regarding access to swedish patient data outside of sweden\nthe legal situation is clear that this is possible provided those appropriate security measures are taken .\nlegal directions regarding whether all wsi data must be stored does not , however , exist ; the swedish law only mandates good and safe health care . \nthe conclusion is that the pathology profession needs to define what the legal mandate means in this case .\nthe swedish pathologist society is now finalizing an official guideline document describing different possible paths , all legal , and all with different advantages and drawbacks .\nthe 2 ndp spanned across many areas of interest with regards to the emerging use of wsi and related it tools in clinical routine .\nfeedback from attendees indicates that this sharing of knowledge and experiences across organizations , disciplines , and sectors is an important catalyst for development of best practices and overall progress .\norganizing ndp 2014 has been a very rewarding experience , and we welcome attendees from all over the globe to future gatherings of this group .", "answer": "techniques for digital pathology are envisioned to provide great benefits in clinical practice , but experiences also show that solutions must be carefully crafted . \n the nordic countries are far along the path toward the use of whole - slide imaging in clinical routine . the nordic symposium on digital pathology ( ndp ) \n was created to promote knowledge exchange in this area , between stakeholders in health care , industry , and academia . \n this article is a summary of the ndp 2014 symposium , including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees .", "id": 15} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlangerhans ' cell histiocytosis ( lch ) is a proliferative disease characterized by monoclonal proliferation and the infiltration of organs with langerhans ' cells .\nseveral organ systems may be involved in lch including the lungs , bone , skin , pituitary gland , liver , lymph nodes , and thyroid .\nlocalized forms of lch in bone have been referred to as eosinophilic granuloma since lichtenstein first described them in 1940 .\nthe term \" pulmonary langerhans ' cell histiocytosis ( plch ) \" was first coined by farinacci in 1951 and refers to disease in adults that affects the lungs , either in isolation or in addition to other organ systems .\nmulti - systemic variants of this disease are known by a variety of names , including systemic histiocytosis x , letterer - siwe disease , and hand - schuller - christian disease . to avoid confusion ,\nthe histiocyte society has established a simplified classification system . according to this system , plch is a disease in adults that affects the lungs , either in isolation or in addition to other organ systems .\nthe most common findings on high - resolution computed tomography ( hrct ) of the chest are multiple nodular and cystic changes , which occur predominantly in the middle and upper lobes .\nnodular lesions are predominant in the early stage of plch and progress to cystic lesions in later stages of the disease . in korea , multiple cystic lesions are the main radiological findings of plch , and no cases with multiple nodular lesions without cysts have been reported . here\n, we report a case of plch with multiple nodules without cysts throughout the lungs .\na 31-year - old male was admitted to our hospital for a cough and exertional dyspnea , which had been present for 2 months . he had no hypertension , tuberculosis , or diabetes , and no history of surgery , medication , or travel .\nhis vital signs were blood pressure 120/80 mmhg , pulse 84/minites , respiration rate 20/minites , and body temperature 37.2. physical examination of the head and neck revealed no palpable cervical lymph nodes or masses and no neck vein engorgement .\nauscultation of the chest revealed a regular heart beat with no murmurs and clear breath sounds with no crackles or wheezing .\nlaboratory examination indicated a white blood count of 10,310/mm , hemoglobin concentration of 16.0 g / dl , and platelet count of 202,000/l , and the chemistry was unremarkable .\narterial blood gas analysis revealed a ph of 7.455 , pao2 99.1 mmhg , paco2 38.2 mmhg , hco3 27 mmol / l , and 98% o2 saturation .\nthe results of the pulmonary function test were forced vital capacity ( fvc ) 5.46 l / minites ( 105% of predicted ) , forced expiratory volume in 1 second ( fev1 ) 4.59 l / minites ( 110% of predicted ) , and fev1/fvc 84% .\nwe performed fiber optic bronchoscopy for bronchoalveolar lavage and observed no abnormal findings in the gram stain or culture , acid - fast bacillus stain or culture , tuberculosis - pcr , or cytology .\nthe chest ct revealed variable - sized nodules with peribronchiolar or centrilobular distribution , some of which revealed thick - walled cavitary change ( fig .\nthe differential diagnosis based on the chest ct findings was that the pulmonary nodules represented hematogenous metastasis .\nhistologically , multiple nodules showed an infiltration of eosinophils , lymphocytes , and langerhans ' cells ( fig .\ntreatment consisted only of smoking cessation , and a chest radiograph 4 months later indicated that the nodules had decreased in size .\nafter 15 months , we observed that the symptoms had improved further , and a follow - up chest radiograph and hrct indicated that the multiple nodules had disappeared ( fig .\nthis case involved a young male who currently smoked and had multiple pulmonary nodules , which were suspicious of metastasis .\nplch is a rare disorder found in only 5% of biopsy - confirmed interstitial lung disease .\nreviewed 102 cases with histopathologically confirmed plch drawn from a group with a mean age of 40.3 years and a 1 : 1.5 ratio of males to females and found that 95% of the cases involved smokers .\nthe only consistent epidemiologic association is cigarette smoking , which is involved in the overwhelming majority ( > 90% ) of cases .\nseveral hypotheses have been proposed to explain the association between cigarette smoking and plch . according to one ,\ncigarette smoke induces the secretion of bombesin - like peptides from neuroendocrine cells in the lungs .\nthese peptides may have an important role in mediating lung injury and consequently induce lung fibrosis .\nother components of cigarette smoke , such as tobacco glycoprotein , have also been implicated in the pathogenesis of plch .\nnevertheless , plch occurs in a very small percentage of smokers , so genetic or environmental factors likely contribute to the development of this disease .\na young male who currently smoked complained of a cough and exertional dyspnea , common clinical features of plch ; however , the radiological findings did not support a diagnosis of plch .\nhrct of the chest is a useful , sensitive tool in the diagnosis of plch .\nthe combination of diffuse , irregularly shaped cystic spaces with small peribronchiolar nodular opacities , predominantly in the middle and upper lobes , is highly suggestive of plch [ 6 - 8,13 ] .\nwhen these features are present on hrct , they allow the clinician to make a diagnosis of plch without a lung biopsy .\nthe lung cysts of plch are often less than 20 mm in diameter and typically have thin walls ( < 1 mm ) [ 6 - 8 ] . the frequency of cystic change reflects the timing of imaging during the course of the disease [ 1,6 - 8 ] . in the early stages ,\nthe most common finding is nodular change , whereas in the later stages , cystic change and fibrosis predominate [ 6 - 8 ] .\nbased on the radiological staging , this case represents an early stage of plch comprised of nodular lesions only without cystic change .\nthis finding is rare ; only one other case of plch with multiple cavitating pulmonary nodules has been reported , although several cases of plch presenting as a solitary pulmonary nodule have been reported worldwide .\nnone of these cases progressed to a more severe stage , such as cystic change or reduced pulmonary function .\nbrauner et al . reported two cases of plch in which only nodules were present : one progressed to cystic change and the nodular lesion disappeared in the other .\nit is thought that predominantly nodular lesions in plch appear early in the reversible state of the disease . in korea ,\na number of cases of plch have been reported based on variable radiological findings , including multiple cysts and a combination of nodules and cysts . however , no case involving only nodular lesions has been reported .\natypical radiological findings as in this case need to be followed to determine whether sarcoidosis , pneumoconiosis , military tuberculosis , hypersensitivity pneumonitis , or metastatic lung nodules are present .\nthe confirmative diagnostic tool is a pathological examination of a lung biopsy . in this case ,\nan open lung biopsy was performed , which resulted in the diagnosis of plch based on positive staining for s-100 protein .\nthe only treatment was smoking cessation , and clinical and radiological improvement was observed 15 months later .\nhere , we report a case of early stage plch in a young male that had atypical radiological features , which consisted of variable - sized nodules only without cystic changes .", "answer": "a 31-year - old man presented with a dry cough and exertional dyspnea . \n the chest x - ray showed multiple nodular opacities throughout the entire lung field . \n chest computed tomography ( ct ) revealed variable - sized nodules with a peribronchiolar or centrilobular distribution , some of which revealed thick - walled cavitary change . based on the chest ct findings , it was initially assumed that metastatic lung nodules with hematogenous spread were present ; therefore , we performed an open lung biopsy . on microscopic examination , \n several compact cellular interstitial infiltrates composed of langerhans ' cells , eosinophils , and lymphocytes were observed . \n immunochemically , the langerhans ' cells showed strong cytoplasmic staining for s-100 protein . \n based on these findings , the patient was diagnosed with langerhans ' cell histiocytosis of the lung . \n high - resolution ct of the chest is a useful , sensitive tool in the diagnosis of pulmonary langerhans ' cell histiocytosis ( plch ) . \n a typical radiologic finding of plch is irregularly shaped cysts . \n the radiological finding in this case of nodular opacities throughout the lung fields only without cysts is rare in plch . \n we report a case of plch with atypical multiple nodules mimicking hematogenous metastatic lung nodules .", "id": 16} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthereby , reconstruction of the last common ancestor ( lca ) to all mollusks , the so - called hypothetical ancestral mollusk , has been hampered by difficulties in recovering fossils of unambiguous molluscan stem species and by the lack of a general agreement concerning the relationships of the various molluscan class - level taxa to each other . as a consequence ,\nmorphology - based analyses have suggested either one or the other of the sclerite - bearing but shell - less aplacophoran clades ( neomeniomorpha or chaetodermomorpha , respectively ) as the earliest molluscan offshoot [ 8 , 9 ] , a monophyletic aplacophora as sister group to all remaining mollusks ( the testaria ) , or a polyplacophoran - aplacophoran assemblage ( aculifera ) as sister to all other mollusks with a primarily univalved shell ( conchifera ) [ 11 , 12 ] .\nthis controversy may soon be settled , however , since two phylogenomic studies have independently confirmed the latter concept , whereby both recovered a monophyletic aplacophora as sister group to polyplacophora ( chitons ) within aculifera [ 4 , 5 ] . in the light of this phylogenetic framework ,\nthe recent description of a cylindrical ( i.e. , worm - shaped ) sclerite- and shell - bearing paleozoic mollusk and the results of integrative molecular - paleontological studies [ 13 , 14 ] have been considered as evidence for the presence of seven or eight shell plates in the lca of crown - group aculiferans . if correct , this implies that the body plan of recent aplacophorans is the result of secondary simplification and thus a derived condition [ 6 , 14 ] . despite additional descriptions of fossils that exhibit a mixture of polyplacophoran- and aplacophoran - like features [ 15 , 16 ]\nthis may be due to the overall paucity of well - preserved paleozoic fossils that undoubtedly can be assigned to the aculiferan lineage , the uncertainty as to whether or not some early ( cambrian or precambrian ) fossils [ 17 , 18 ] indeed represent crown- or stem - group mollusks , and the fact that solid morphological and developmental evidence from recent aplacophoran representatives is still largely lacking\n. the few reports of individual aplacophoran larvae and postlarvae have shown that these animals may bear six or seven rows of papillae , sclerites , or sclerite - secreting cells [ 1921 ] , but these studies found no further support by gross morphological developmental studies of two neomeniomorph representatives [ 22 , 23 ] .\nthe muscular architecture of mollusks is intimately associated with the existence , number , and arrangement of shells in the respective taxa . in polyplacophorans ,\nthe myoanatomy is highly complex [ 7 , 25 ] ( figures 1a and 1c ) and several components , such as a laterally positioned enrolling muscle and a dorsal rectus system that spans the longitudinal axis of the animal , have been widely considered as defining morphological features ( autapomorphies ) of this taxon . in stark contrast to the sophisticated polyplacophoran myoanatomy , aplacophoran representatives have a much simpler muscular organization that , together with the body wall musculature , mainly comprises serially repeated dorsoventral muscles ( figures 1b and 1d ) .\naccordingly , a scenario that suggests a shell plate - bearing aculiferan lca with polyplacophoran - like musculature implies drastic secondary simplification of the muscular body plan of aplacophoran mollusks . since ontogenetic data may provide important insights into the evolutionary history of a given taxon [ 26 , 27 ] , we investigated the development of a model neomeniomorph aplacophoran , wirenia argentea , from hatching of the larvae until after metamorphosis . in comparing myogenesis in wirenia with that of a polyplacophoran ( leptochiton asellus )\n, we found striking similarities in the muscular organization of both species ( see table 1 for a summary of major larval and adult muscle systems known for the various molluscan lineages ) , including the presence of a rectus muscle ( figures 2a2d ) , so far only known from polyplacophorans , and a laterally positioned enrolling muscle ( figures 2a2h ) .\nboth systems are retained in adult polyplacophorans but are lost during wirenia postlarval development ( note that some neomeniomorphs do exhibit distinct enrolling muscles as adults [ 28 , 29 ] ) . although homology between the polyplacophoran and neomeniomorph enrolling muscles has been questioned , their similar position in the respective animals and , in particular , their identical mode of ontogenetic formation as independent muscle system ( and not as a thickened derivative of the body wall musculature , as proposed earlier for the aplacophoran taxa ) argue strongly for their common evolutionary origin and thus for the presence of such a system in the lca of both clades . aside from these muscles\nboth systems are only transiently present in advanced larvae , and neither has a counterpart in either the polyplacophoran or the neomeniomorph adult body plan . as with the rectus and the enrolling muscles , the identical positions of the ventrolateral and the ventromedian muscles in wirenia and leptochiton larvae , together with their identical positions relative to other muscles , clearly suggest that these respective muscles are homologous between the two species ( see for a recent overview on homology theory and assessment ) . earlier , we had already found the ventrolateral system in larvae of another polyplacophoran , mopalia muscosa , but had overlooked the ventromedian muscle .\nreinvestigation of the original 3d data set , however , unambiguously revealed such a muscle also in mopalia ( data not shown ; available on request ) .\naccordingly , it appears highly likely that the ventrolateral and the ventromedian muscles together with the enrolling and the rectus muscle were all part of the muscular toolkit of the lca of polyplacophorans and neomeniomorphs , and that the simple myoanatomy of adult wirenia is a derived , secondary condition .\nformation of the eight sets of dorsoventral muscles in polyplacophorans passes through a transitory stage of multiple individual myocytes that appear synchronously ( figure 2e ) and give rise to the first seven paired shell muscle units ( while the eighth set forms considerably later , together with the most posterior shell plate ) .\nin wirenia , seven pairs of dorsoventral muscles develop simultaneously ( figures 3a3e ) and differentiate further in later stages ( figure 2f ) .\na gradual numerical increase of the dorsoventral muscle sets was observed only after metamorphosis ( figure 3f ) .\naccordingly , both neomeniomorphs and polyplacophorans exhibit a transient stage of seven - fold seriality in the arrangement of these muscles . despite the different ontogenetic pathways that lead to this seven - fold seriality ( fusion of multiple myocytes in polyplacophorans versus simultaneous formation in wirenia )\n, this seven - fold seriality appears to be a reoccurring pattern , at least in aculiferan mollusks ( unfortunately , the ontogenetic sequence of the formation of the eight pairs of dorsoventral muscles in monoplacophora is still unknown ) .\nthis is well in line with the description of the seven - shelled fossil kulindroplax , as well as with the serially arranged sclerites or papillae of some recent aplacophorans [ 1921 ] , and lends further support for an aculiferan lca with a seven - fold seriality of epidermal hardparts and the associated musculature .\nthis implies that the eighth set of dorsoventral muscles of recent polyplacophorans is a derived condition .\nthe late formation of the most posterior shell plate and associated musculature in polyplacophorans [ 7 , 31 ] may well be considered as ontogenetic testimony of such a scenario .\nthe rudimentary data on myogenesis ( and development in general ) of the second aplacophoran taxon , the chaetodermomorpha , does not allow for definite conclusions concerning the presence of neomeniomorph- and/or polyplacophoran - like features such as the rectus or the ventromedian muscles in the lca of this taxon .\nhowever , the ring musculature in the body wall of both aplacophoran clades , which is also rudimentarily present in the apical region of polyplacophoran larvae ( figure 2 ) , may constitute an aculiferan apomorphy uniting polyplacophora , neomeniomorpha , and chaetodermomorpha ( table 1 ) .\nthis , together with the cylindrical shape of the aplacophorans and the polyplacophoran larva as well as the fossil kulindroplax , argues for a worm - like body shape of the lca of aculifera , rendering the dorsoventrally flattened appearance of recent polyplacophorans a derived condition .\nthe paired lateral longitudinal muscle in the larva of the chaetodermomorph chaetoderma may correspond to either the enrolling or the ventrolateral muscle of larval polyplacophorans and neomeniomorphs ( table 1 ) , which would further support the inclusion of chaetodermomorpha within aculifera .\nthe fact that kulindroplax shares morphological features not only with polyplacophorans but also with recent chaetodermomorphs , including the absence of a pedal pit and the position of the gills , likewise supports such a scenario .\nwhether or not a monophyletic aculifera will stand the test of future phylogenetic analyses or whether chaetodermomorpha , despite these shared morphological characters , will be proven to have different affinities remains to be seen .\nthe transient expression of typical polyplacophoran - like muscles in the wirenia larva , however , strongly suggests that at least neomeniomorph aplacophorans stem from an ancestor with polyplacophoran - like features that most likely also included seven shell plates .", "answer": "summarymollusca is an animal phylum with vast morphological diversity and includes worm - shaped aplacophorans , snails , bivalves , and the complex cephalopods [ 1 ] . \n the interrelationships of these class - level taxa are still contentious [ 2 , 3 ] , but recent phylogenomic analyses suggest a dichotomy at the base of mollusca , resulting in a monophyletic aculifera ( comprising the shell - less , sclerite - bearing aplacophorans and the eight - shelled polyplacophorans ) and conchifera ( all other , primarily univalved groups ) [ 4 , 5 ] . the aculifera concept has recently gained support via description of the fossil kulindroplax , which shows both aplacophoran- and polyplacophoran - like features and suggests that the aplacophorans originated from a shelled ancestor [ 6 ] , but the overall morphology of the last common aculiferan ancestor remains obscure . here \n we show that larvae of the aplacophoran wirenia argentea have several sets of muscles previously known only from polyplacophoran mollusks . \n most of these are lost during metamorphosis , and we interpret them as ontogenetic remnants of an ancestor with a complex , polyplacophoran - like musculature . \n moreover , we find that the first seven pairs of dorsoventral muscles develop synchronously in wirenia , similar to juvenile polyplacophorans [ 7 ] , which supports the conclusions based on the seven - shelled kulindroplax . \n accordingly , we argue that the simple body plan of recent aplacophorans is the result of simplification and does not represent a basal molluscan condition .", "id": 17} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin this case report , we describe a case of asherman 's syndrome treated with adult autologous stem cells for endometrial regeneration that resulted in conception after in vitro fertilization - embryo transfer ( ivf - et ) .\nthe basis of this case is that endometrium is a dynamic , cyclically regenerating tissue , a unique model of physiological angiogenesis in adults .\nangiogenesis results either from sprouting of new vessels through recruitment of local endothelial cells from neighbouring blood vessels and/or by endothelial progenitor cells circulating in the peripheral blood after release from the bone marrow.[14 ] bone marrow stem cells also contribute to regeneration of the endometrium . on the basis of these facts ,\nher past treatment included a dilatation and curettage ( d and c ) in february 2005 .\nshe presented to us with infertility and scanty menstruation since her d and c. her first transvaginal ultrasound scan on day 3 of the menstrual cycle revealed normal size retroverted uterus with homogenous myometrium and thin single line endometrium , but intact endometriomyometrial junction .\nthe left ovary measured 2.52 2.51 3.04 cm , had two antral follicles and a hemorrhagic cyst , and was adherent to uterus posteriorly .\nright ovary measured 2.55 1.22 1.84 cm and had only one antral follicle .\ndoppler studies showed very poorly vascularised ovaries , even with minimum wall filter , pulse repetition frequency of 0.3 , and gains -0.8 .\na repeat scan on day 14 revealed that hemorrhagic cyst in left ovary had regressed partially .\nright ovary showed a follicle of 20 mm which on color doppler showed vascularity covering more than three - fourth of the follicular circumference with resistance index ( ri ) of 0.47 and peak systolic velocity ( psv ) of 11.23 cm / s , but the endometrium was only 3.2 mm with branches of spiral vessels seen only up to endometrio - myometrial junction .\nfollow - up scan after three days still showed the same endometrial picture though follicle had ruptured .\nmidluteal ultrasound scan ( ninth day post ovulation ) showed that endometrium had failed to grow even during secretory phase , despite corpus luteum with vascular ring covering more than half of the corpus luteal circumference with ri of 0.43 and psv of 10.43 cm / s on right side .\nsevere endometrial adhesions were seen , which were cut [ figures 1 and 2 ] .\nhysteroscopic picture - endometrial adhesions postadhesiolysis hysteroscopic picture iucd - cu t was placed to maintain surgically established patency of the endometrial cavity .\nshe was treated with cyclical estrogen and progesterones with ethinyloestradiol 0.05 mg from fifth to 25 day of the cycle and with medroxy progesterone acetate 10 mg from 20 to 25 day for 6 months to obtain a functional endometrium . during this period , she had withdrawal bleeding , which was scanty .\nultrasound assessment of the endometrium in the following cycle showed no growth of the endometrium in the periovulatory and secretory phase of the menstrual cycle despite normal follicular development , rupture , and corpus luteum formation .\nthin endometrium after removal of iucd in preovulatory period due to poor endometrial development , she was advised surrogacy with ivf .\nher fsh on day 3 of cycle was 19.70 iu / ml with an antral follicle count of 2 . in view of poor ovarian reserve ,\nshe was given oral oestradiol valerate tablets in increasing doses from 4 mg daily for 3 days , followed by 6 mg daily for another 3 days , and then 8 mg daily for a total of 25 days along with aspirin 75 mg daily for endometrial preparation .\nultrasound scans were done intermittently to assess the endometrium , but it never reached a thickness more than 3.6 mm .\nthis hormone replacement therapy cycle was repeated for 6 months without improvement of the endometrium . based on reports of adult autologous stem cells applications for regeneration of\ninjured cartilage and cardiomyocytes in cardiac infarction , it was thought that use of stem cells for regeneration of endometrium was worth trying , especially because endometrium naturally has a regenerating capacity .\nif the basal layer of the endometrium is repaired and further stimulated , it should increase in thickness .\non june 15 , 2009 , her bone marrow aspiration was done from the iliac crest under local anesthesia maintaining strict asepsis .\naspiration was done using bone marrow biopsy needle and 10 ml syringe prewashed with heparin .\ncollection was done in cpda ( citrate - phosphate dextrose anticoagulant ) medium using 1 ml of medium for 7 ml of bone marrow .\nit was sent to a dedicated stem cell laboratory working as per clinical gmp / gtp standard and having a working area with laminar airflow to class 100 .\nbone marrow was centrifuged using histopaque density gradient at 1000 rpm for 10 mins and 102 million mononuclear cells were separated .\nthese cells were further treated by column separation technique and customized cocktail of cd9 , cd90 , and cd133 antibodies was used for immunomagnetic isolation of endometrial angiogenic stem cells .\ngene expression study for cd9 , cd44 , and cd90 using rt - pcr technique was done for differentiated cells .\ntotal 39 million marker - positive endometrial angiogenic cells were supplied in 0.7 ml of pbs ( phosphate buffer saline ) with 2% autologous ( patient 's own ) heat - inactivated serum on the next day for transplant.[616 ] patient was called with partially filled bladder on june 16 , 2009 , second day of her menstrual cycle .\ncurettage was done under anesthesia . with patient in lithotomy position , sim 's speculum in place ,\nanterior retractor was used to retract the anterior vaginal wall , and volsellum was used to hold the anterior lip of cervix .\nfrance ) attached with 1-ml syringe , filled with 0.7-ml stem cell suspension , was advanced through cervix upto the fundal end of the endometrium under transabdominal ultrasound guidance .\nwhen the tip of the catheter was 0.5 cm below the fundus , piston was slowly advanced to allow slow steady flow of cell suspension in the uterine cavity . after instilling 0.3 ml of stem cell suspension at the fundus , injection was continued when cannula was gradually withdrawn out , till the tip reached mid cavity of the uterus .\nit was further very gently and slowly withdrawn out of the internal os and then external os , maintaining continuous pressure on the piston to prevent any back flow .\nspeculum and volsellum were removed , and patient was shifted when she recovered from anesthesia .\nshe was given oestradiol valerate 6 mg daily , starting on the same day for 25 days .\nultrasound was done on 14 day and 19 day of the cycle , which showed endometrial thickness of 5.0 and 5.2 mm , respectively , and color doppler showed spiral vessels reaching subendometrial zone .\nultrasound scans done at midcycle showed improvement in endometrial thickness , morphology , and vascularity [ figure 4 ] .\nwell - developed endometrium with low - resistance vascularity reaching zone 4 on november 2 , 2009 , endometrial thickness at ultrasound was 6.9 mm , with vascularity reaching intraendometrial region .\nthere were dominant follicles in either ovary , which excludes the possibility of any endogenous luteinizing hormone surge . on november 6 , 2009 ,\nthree 4 - 6 cell grade i donor oocyte ivf embryos were transferred . at this time , her endometrium was multilayered , with thickness of 7.1 mm and intraendometrial vascularity .\nshe was given progesterone vaginal gel ( crinone 8% , manufactured by fleet laboratories , uk , marketed by merck serono ) twice a day after et , as luteal support and ethinyl oestradiol was continued in a dose of 6 mg daily along with aspirin 75 mg daily .\nonce -hcg was positive , the dose of oestradiol valerate was increased to 8 mg daily .\nprogesterone vaginal gel 8% was continued twice a day along with aspirin 75 mg daily .\na single gestational sac of 12 mm , yolk sac of 2.9 mm , embryonic pole of 2.4 mm , with m - mode showing embryonic heart rate of 112/mt were seen at ultrasound on november 30 , 2009 .\nfollow - up scan was done at 8 weeks of pregnancy which showed a healthy fetus [ figures 57 ] .\ngestational sac , yolk sac , and embryonic pole after embryo transfer and positive -hcg test m - mode of cardiac activity of embryo 3d picture of 8 weeks scan\nthis was a case of infertility with severe asherman 's syndrome and bilateral cornual tubal block with low ovarian reserve . anti - mullerian hormone , which is now considered to be the most reliable marker for ovarian reserve , was not routinely used at that time ( 2007 ) and was not easily available locally , and therefore was not done .\nlow ovarian reserve with blocked fallopian tubes had left her with an option of oocyte donation .\nplacement of iucd after surgery and cyclical hormonal therapy in association with low - dose aspirin or nitroglycerine is an established protocol for development of functional endometrium .\nplacing iucd after curettage , followed by cyclical oestrogen progesterone therapy with aspirin , could not improve her endometrium .\nstem cells derived from tissues such as bone marrow , cord blood , adipose tissue , or the amniotic fluid have demonstrated regenerative potential in a variety of diseases and degenerative disorders . therefore , we tried to regenerate the endometrium with adult autologous stem cells after curettage , which was further supported with cyclical estrogen , progesterone , and aspirin for improving vascularization .\nbone marrow aspiration is fairly safe procedure with the risk of bleeding or infection , which are extremely rare when done meticulously in the hands of the expert .\ncurrettage was done to evoke injury - induced inflammatory reaction and hyperemia as homing induction , which in turn would enhance the response of endometrium to cyclical hormones .\nwe would like to qoute a study that has shown regeneration of injured endometrium using adult bone marrow cells . \ndonor - derived bone marrow cells have been identified in human uterine endometrium. recent evidence has implicated bone marrow - derived cells as possible endometrial progenitors .\nit is unknown whether these cells originate from bone marrow mesenchymal stem cells or , alternatively , are circulating endometrial cells originally derived from the endometrium and harbored in bone marrow .\nthese cells , regardless of their origin , may serve as a source of reparative cells for the reproductive tract .\nthese data show the potential for stem cells to have a role in the regeneration or repair of this tissue after injury .\nsignificant engraftment of endometrium by bone marrow is likely to occur after endometrial injury or inflammatory insult .\nadditionally , the proliferation and development of endometrium are entirely regulated by hormonal stimuli . ovarian estrogen and progesterone drive endometrial growth and apoptosis . in the case described in this study ,\nwe tried to regenerate the endometrium by endometrial angiogenic stem cells isolated from autologous adult stem cells and transplanting them in the endometrium immediately after curettage .\nthis was based on a study that describes that mononuclear cells collected from the menstrual blood contains a subpopulation of adherent cells and retains expression of the markers cd9 , cd29 , cd41a , cd44 , cd59 , cd73 , cd90 , and cd105 ; the markers used were cd9 , cd44 , and cd90 to isolate the desired cells .\nthere is a minimal risk of developed cells presenting certain other markers during the process , but immunomagnetic isolation with specific marker antibodies reduces this possibility .\nthis experimental therapy may be tried on larger scale when the basal layer of endometrium is also damaged by surgical insult .\nthe risk for malignancies after the use of adult autologous stem cells may be a concern in view of several reports , but we would like to draw attention to the fact that most of these reports discuss the cases where adult autologous stem cells were used to treat malignancies .\nthe total cost of the therapy in an indian set up comes to approximately rs .\n50 000 ( rupees fifty thousand ) , excluding the expense of ivf - et .\nmoreover , it has an emotional and social advantage that the patient can bear her own child as against surrogacy .\nto the best of our knowledge , no case of asherman 's syndrome conceived after endometrial regeneration with adult autologous stem cells after failure of all other conventional modes of treatment has been reported in literature .\nthis therapy can be used as an alternative to surrogacy in females with severe asherman 's syndrome , though larger trials may be needed to establish this as proved line of treatment .", "answer": "in a woman with severe asherman 's syndrome , curettage followed by placement of intrauterine contraceptive device ( iucd ) ( iucd with cyclical hormonal therapy ) was tried for 6 months , for development of the endometrium . \n when this failed , autologous stem cells were tried as an alternative therapy . from adult autologous stem cells isolated from patient 's own bone marrow \n , endometrial angiogenic stem cells were separated using immunomagnetic isolation . \n these cells were placed in the endometrial cavity under ultrasound guidance after curettage . \n patient was then given cyclical hormonal therapy . \n endometrium was assessed intermittently on ultrasound . on development of endometrium with a thickness of 8 mm and good vascularity , in vitro \n fertilization and embryo transfer was done . \n this resulted in positive biochemical pregnancy followed by confirmation of gestational sac , yolk sac , and embryonic pole with cardiac activity on ultrasound . \n endometrial angiogenic stem cells isolated from autologous adult stem cells could regenerate injured endometrium not responding to conventional treatment for asherman 's syndrome .", "id": 18} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynthesis of Stereodefined 1,1-Diborylalkenes via Copper-Catalyzed Diboration of Terminal Alkynes\n\nPaper sections:\n\nAlkenyl boronic acids and their derivatives are non-toxic, shelf-stable organometallic compounds that react with high fidelity in a range of C-C and C-heteroatom couplings, making them useful reagents in organic synthesis. 1 1,1-Diborylalkenes are an emerging subclass that offer exciting potential for accessing multisubstituted olefins in a stereocontrolled manner through sequential reaction at each of the two C-B bonds. 2 To this end, many approaches to synthesize 1,1-diboryl alkenes bearing two -Bpin groups (Bpin = pinacolatoboryl) have been developed from alkene 2c,3 and alkyne starting materials. 4 When such compounds are then employed in cross-coupling, the inherently similar reactivity of the two C-Bpin bonds makes it challenging to achieve high selectivity for a mono-functionalized product. Indeed, successful mono-selectivity at the less hindered position has only been demonstrated when the 1,1-diborylalkene contains an aryl group at the 2-position and when an aryl iodide is employed as the electrophile (Scheme 1 A). 2c,4b We reasoned that the scope of substrates and coupling partners could be expanded if the two boron centers were differentially protected with one -(pin) (pin = pinacolate) and one -(dan) (dan = 1,8-diaminonaphthalenyl) group (Scheme 1 A). The Bdan group is well known to possess diminished Lewis acidity, and to be generally inactive toward transmetalation, a key step of cross-coupling. 5 This so-called protected boron moiety can be reactivated by either deprotection under acidic condition, 5 or interaction with KOtBu or Ba(OH)2. 6 The sequential masking/unmasking strategy enabled by the Bdan group has been successfully applied to iterative cross-coupling, providing efficient and concise approaches to functional organic molecules including complex oligorenes, 5a-c,6c and optoelectronic materials. 5d Moreover, these isomerically pure 1,1-diborylalkenes represent a promising class of prochiral substrates to generate enantioenriched 1,1-diborylalkanes, 7 that are valuable versatile building blocks to access enantioenriched functionalized alkanes. 8
In view of the unique synthetic value of differentially protected 1,1-diborylalkenes, practical synthetic methods to access such complexes in a stereodefined manner are desirable. However, few methods are currently available. In 2017, Chirik and colleagues described a Co-catalyzed 1,1-diboration of aliphatic alkynes to synthesize (Z)-1,1-diborylakenes with use of the mixed diboron reagent pinB-Bdan (Scheme 1 B). 4b Later, Marder reported a base-catalyzed stereoselective diboration of alkynyl esters and amides with pinB-Bdan (Scheme 1 C). 9 Both methods, though highly enabling in their own right, have limited substrate scope and only provide access to the Z-configured products. Driven by our interest in developing new metal-catalyzed alkyne difunctionalization methods, we recently reported a CuH-catalyzed cascade process to access enantioenriched \u03b1-aminoboron compounds via sequential hydroboration and hydroamination of terminal alkynes. 10 Here we report an exclusively E-selective Cu-catalyzed three-component reaction to produce 1,1-diborylakenes through a tandem sequence comprised of dehydrogenative C(sp)-H borylation with HBdan and hydroboration of the resulting alkynylBdan intermediate with HBpin (Scheme 1 D).
Our investigation commenced by examining reaction conditions using phenylacetylene (1a) as pilot substrate, with HBdan and HBpin as coupling partners. After extensive optimization, we identified an effective protocol in which HBdan is first mixed with 1a in the presence of 5 mol% Cu(OAc)2 and 5 mol% (Ra)-DTBM-SEGPHOS in THF for 15 min. After this period HBpin is added, and the reaction is allowed to stir for an additional 16 h at room temperature, at which point the desired product 2a is isolated in 69% yield. (Table 1, entry 1) The timing of HBpin addition was found to be important. The yield of 2a decreased when HBpin added earlier, with larger amount of side products observed (Table 1, entries 2-3).
\n\nunderdeveloped\nAnother key finding from these studies was that acetate counteranion and (Ra)-DTBM-SEGPHOS ligand were both required (Table 1, entries 4-12). CuOAc was slightly less effective than Cu(OAc)2 (Table 1, entry 4), while other copper sources such as CuBr and CuCl, together with NaOtBu, showed no catalytic activity. In terms of other ligands tested, (Ra)-DM-SEGPHOS gave slightly lower yield of 2a than (Ra)-DTBM-SEGPHOS (Table 1, entry 12). Other phosphine ligands unfortunately led to either low yield or no reaction. There was no reaction in the absence of a ligand (Table 1, entry 13). The structure and (E)-stereochemical configuration of 2a were unambiguously assigned by X-ray crystallography ( Standard reaction conditions: 1a (0.10 mmol), HBdan (0.11 mmol), HBpin (0.12 mmol), Cu(OAc)2 (5 mol%), and (Ra)-DTBM-SEGPHOS (5 mol%) in THF (0.25 mL). b 1 H NMR yield using CH2Br2 as internal standard. c 10% of PhCHCH(Bpin) was also observed. d Together with NaOtBu (10%). e 9% of PhCHC(Bpin)2 was observed.
Next, we evaluated the scope and functional group compatibility of this stereoselective process (Table 2). The reactions with aryl-substituted alkynes were found sensitive to both electronic and steric effects. Aryl acetylenes with electron-donating groups normally performed better than those with electron-withdrawing groups. For example, p-MeO-substituted phenylacetylene gave product 2c in 70% yield, while p-CF3substituted phenylacetylene gave product 2f in 47% yield. Diboration of para-substituted phenylacetylenes generally occurred smoothly while meta-and ortho-substituted phenylacetylenes gave relatively low yield. A range of functional groups, such as halides (2e, 2k, 2l, 2m), an ester (2g), ethers (2c, 2i) and amines (2d, 2j), were well tolerated. 2-Ethynylnaphthalene and 3-ethynylthiophene underwent diboration as well to give corresponding 1,1-diborylalkenes (2h, 2n).
1,1-Diboration was similarly effective with aliphatic alkynes, furnishing the corresponding E-configured products as well. The structure of 1,1diborylalkene 2o was confirmed by X-ray crystallography (Table 2, bottom left). Remarkably, 1-ethynylcyclohexene underwent 1,1-diboration to furnish product 2s with C=C double bond intact. Functional groups like carbonate (2p), ether (2q) and silyl ether (2t) were tolerated with products isolated in useful yields. Conditions: 0.10 mmol scale, THF (0.25 mL). Percentages correspond to isolated yields.
Interestingly, when terminal alkynes 1 were reacted with 2.2 equiv HBdan in the absence of HBpin, 1,1-homodiboration proceeded smoothly, furnishing 1,1-diborylalkenes 4 bearing two -Bdan groups in excellent yields (eq. 1).
To illustrate the practical utility of this procedure, we performed stepwise Suzuki-Miyaura cross-couplings of 1,1-diborylalkenes (Scheme 2). The selective monoarylation of 2a worked well using 4-iodotoluene as coupling partner under standard cross-coupling conditions, giving 92% 5a after 12 h at 30 \u00b0C. Notably, the reaction with 4-bromotoluene also proceeded, albeit at a higher temperature of 80 \u00b0C, giving product 5a in 85% yield with no diarylation product detected. Next, the Bdan group of 5a was deprotected, and the resulting boronic acid was carried forward without purification in a second cross-coupling reaction with 4iodoanisole to produce triarylated alkene 6a as a single stereoisomer.
\n\nScheme 2.\nStepwise Suzuki-Miyaura coupling reactions of 2a.
Having established the scope and utility of the (E)-selective alkyne 1,1diboration method, we shifted our attention to investigating the reaction mechanism. Subjecting sterically bulky mesitylacetylene to the standard reaction conditions did not lead to formation of the typical 1,1-diboryalted product; instead, alkynylBdan 3u was isolated in 55% yield (eq. 2). This result suggests that alkynylBdan is the product from first step of the tandem process and that the second hydroboration step is sensitive to steric hindrance. Consistent with this notion, the reaction between 2a and HBdan before addition of HBpin was monitored by 1 H NMR spectroscopy (eq. 3), and 16% alkynylBdan 3a and H2 were both observed after 30 min (SI, Figure S1). To further support our hypothesis, the proposed intermediate 3a was independently synthesized and submitted to the reaction with HBpin under the standard conditions. Hydroboration of 3a proceeded smoothly to furnish 2a in 60% yield (eq. 4).
\n\nequiv\nBased on our experimental observations and previous reports, 11-13 a Cucatalyzed tandem process comprised of dehydrogenative borylation of terminal alkynes and following hydroboration is proposed (Scheme 3).
[LCuOAc] a1, generated by reduction of Cu(OAc)2 in the presence of phosphine, 14 reacts with terminal alkynes to give the alkynylcopper intermediate a2 and HOAc. 13b,15 Following \u03c3-bond metathesis between a2 and HBdan gives alkynylBdan 3 and [LCuH] a3. 11,16 syn-Insertion of a3 to intermediate 3 generates alkenyl copper species a4, 12,13,17 which then undergoes \u03c3-bond metathesis with HBpin to furnish the (E)-1,1-diborylalkenes and regenerate [LCuH] a3.
Under the optimal conditions, prior to addition of HBpin, the right cycle alone proceeds through several turnovers to build up 3a, and upon addition of HBpin the left cycle turns on. This strategy limits the formation of side products caused by the high reactivity of HBpin. In the 1,1-homodiboration system with HBdan only, both cycles presumably proceed in parallel. 18
In conclusion, we have reported the first (E)-selective synthesis of 1,1diborylalkenes bearing one -Bpin group and one -Bdan group from terminal alkynes via a Cu-catalyzed tandem process. A wide range of aryland alkyl-substituted alkynes underwent this transformation, giving the corresponding 1,1-diborylalkenes with broad functional group tolerance. We have also demonstrated that differentially protected 1,1-diborylalkenes are useful synthetic intermediates for the construction of multi-substituted alkenes with stereocontrol. Further applications of 1,1-diborylalkenes for the synthesis of more complex compounds are being pursued in our laboratory.
Scheme 3. Proposed mechanism.
\n\nSupporting Information\nThe Supporting Information is available free of charge at DOI: [filled later]. Detailed experimental procedures and compound characterization (PDF) Crystallographic data for 2a (CIF) Crystallographic data for 2o (CIF)
\n\nAUTHOR INFORMATION\nCorresponding Author *E-mail: keary@scripps.edu
\n\nORCiD\nYang Gao: 0000-0001-9270-6251 Keary M. Engle: 0000-0003-2767-6556
\n\nNotes\nThe authors declare no competing financial interests.
", "answer": "ration of terminal alkynes is described. The tandem process involves sequential dehydrogenative borylation of the alkyne substrate with HBdan (HBdan = 1,8-diaminonaphthalatoborane), followed by hydroboration with HBpin (HBpin = pinacolborane). This method proceeds efficiently under mild conditions, furnishing 1,1-diborylalkenes with excellent stereoselectivity and broad functional-group tolerance. Taking advantage of the different reactivities of the two boryl moieties, the products can then be employed in stepwise cross-couplings with aryl halides for the stereocontrolled construction of trisubstituted alkenes.", "id": 19} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsnoring is not a benign symptom . it is associated with an increased risk of hypertension , cardiac arrhythmias , and mortality .\nsnoring is defined as a sound produced when an individual breaths during sleep due to the turbulence of air passing through the partially obstructed airway .\nit is considered as one of the most common clinical symptoms of obstructive sleep apnea ( osa ) .\nsnoring may result in excessive daytime sleepiness , loss of concentration , and psychological disturbances that may eventually cause deterioration of the patient life quality unless treated .\nthis wide range is due to the differences in the populations studied , study design , investigations performed , ethnic group , age , and sex of the subjects .\nsnoring is potentially related to the increase in the body mass index ( bmi ) , cigarette consumption , ethnic differences , infections , and hypertension .\nnocturnal polysomnography is considered the best tool to investigate whether snoring is a health risk .\nhowever , it is not widely available and expensive to be used as a screening tool , as it is mostly available only in specialized sleep clinics .\ntherefore , the use of questionnaires like berlin questionnaire become a simple and effective method of screening for snoring and risk of osa .\nin addition , many craniofacial features and malocclusions were reported to be associated with snoring .\nfor example ; narrow airway at the level of the soft palate and oropharynx , more inferiorly positioned hyoid bone , more protruding maxilla , anterior - posterior discrepancy of maxilla and mandible , class ii malocclusion , increase in over - jet , reduced overbite , narrower upper , and shorter lower dental arch and crowding in the mandibular arch .\naccording to literature , snoring was associated with osa , and the characteristics were complicated with other dentofacial risk features such as facial profile , malocclusion classification , and dental arch morphology .\nfor instance , stellzig - eisenhauer and meyer - marcotty ( 2010 ) reported a significant difference between patients with retrognathism and pragmatism in respect to the transverse dimension of the nasopharynx .\nhowever , de freitas et al . , found no correlation between obstructions of the upper airway and the frequency of malocclusions .\nthis reflects the discrepancy between the influence of the facial profile , malocclusion classification , and dental arch morphology on airway measurements .\ntherefore , the aim of this study was to test the null hypothesis that there is no morphological difference in facial profile , malocclusion class , and dental arch morphology in adult yemenis male with and without snoring .\nrejection of the null hypothesis might improve our understanding of the influence of snoring on the surrounding dentofacial structures .\nafter the study was approved at the institutional level and informed consent was obtained , a cross - sectional study was carried out among male students and employees at the university of science and technology . for the prevalence study ,\nthe sample size was calculated using power and sample size software ( 5.2 mb version 2.1.31 . ) which indicated 840 subjects is required for this study . when the participants agreed to participate in the study\n, a consent form was given along with a set of the sleep behavior questionnaire ( berlin questionnaire ) .\nthe inclusion criteria were : age 18 and above , healthy individuals without any diseases or congenital abnormalities and the presence of at least six teeth in each maxillary and mandibular arch .\neach selected subject undergone clinical examination , upper and lower arch impression , and bmi calculation .\ntotally , 150 participants ( 75 snorers : 9 employees , 66 students ) and ( 75 nonsnorers : 8 employees , 67 students ) were able to complete their required records .\nbmi was calculated from the patient 's height and weight in standard units ( kg / m ) , and neck circumference ( nc ) was measured at the level of the thyroid cartilage .\nthe facial profile was assessed by classifying the facial profile into convex , concave , and straight .\nassessment of arch morphology and palatal morphology were carried out as following : arches were classified as constricted and nonconstricted . the dental arch constriction was defined as the presence of two or more maxillary posterior teeth in edge to edge cuspal relationship with their antagonists , or in a frank cross bite .\nthe palatal morphology divided into u - shaped ( normal ) and v - shaped ( constricted ) .\nmaxillary constriction was defined by the presence of all the following features : a narrow and high palatal vault ; corresponding narrow arch form and unilateral or bilateral buccal tilting of the maxillary alveolar arches with posterior teeth in crossbite or edge to edge relationship with the lower teeth .\nassessment of dental cast parameters were completed by taken dental impression and fabricating a set of upper and lower models .\nalginate impression material ( zhermack , germany ) mixed according to the manufacturer 's instructions .\nthe following measurements were recorded using digital calipers : inter - canine distance ; inter - premolar distance ; intermolar distance ; arch length ; palatal cast depth .\nout of 840 questionnaires distributed , 700 were returned ( 77 employees and 623 students ) ; the response rate was 80% .\nnine were employees ( 11.7% ) , and 105 were students ( 16.9% ) . totally ,\n150 participants ( 75 snorers ) and 75 nonsnorers were able to complete their required records and , therefore , were included in the comparison study .\ntable 1 shows the demographic profile of 150 subjects who were males with mean age of 24 4 years , mean height of 167 6 cm , mean weight of 63 10 kg , mean bmi of 22.5 3 kg / m , and mean nc 36 2.6 cm .\nclinical observation of snorers and non - snorers extra - oral variables accordingly , the mean neck size was found to be significantly greater for the snorer group ( 36.6 2.5 ) than nonsnorer group [ 35.4 2.6 ; p < 0.007 ; table 1 ] .\nclinical examination shows that the most frequent finding among snorer groups when compared with the nonsnorer group were straight profiles ( 52.0% ) , class i malocclusion ( 74.7% ) , and v palatal shape ( 16.0% ) , respectively [ table 2 ] .\nthe chi - square test revealed a significant difference among the v - shape palatal morphology ( p < 0.034 ) , but no significance was found in terms of the facial profiles ; malocclusion class or arch morphology .\nin addition , the upper arch length was significantly shorter ( 35.6 2.5 ) in the snorer subjects than the nonsnorer group ( 36.4 2.5 ; p < 0.038 ) , and the inter- first upper premolar distance was significantly narrower ( 39.6 2.6 ) in the snorer subjects than in the nonsnoring group [ 40.8 2.9 ; p < 0.013 ; table 3 ] . orthodontic observation of facial profile , malocclusion class , arch morphology and palatal shape orthodontic observation of dental cast measurements ( meansd ) in snorers and non - snorers\nthe present study was carried out to determine the prevalence of snoring among male adult at university population setting and to compare the craniofacial features of an adult with and without snoring using clinical examination .\nin addition , the clinical examination showed that the snoring in our adult university population manifested a significantly different craniofacial feature , such as a v - shaped palate ; higher nc ; lower upper arch length ; and a decrease in the inter- first upper premolar distance . based on our prevalence of snoring result , it seems that the prevalence of snoring in our sample is slightly higher from the average of snoring prevalence quoted earlier but lesser compared with the other studies in student population .\ntable 4 summarized previous studies of snoring among the student population . comparing our result to malaysian medical students ,\nour result showed a higher percentage of snoring , which might be due to a mixture of students and employees in our sample ; different age ; and bmi and diverse definition of snoring .\nconcluded that snoring was prevalent in student population , and male gender showed a trend as an independent predictor for snoring , which is similar to our result .\nsummery of snoring among the student population ( from most to least severe ) when we compared our result with the general adult population findings , our result is slightly lower than the prevalence of snoring reported by middle - eastern studies ( 52.3% saudi and 28.7% jordanian bahammam et al . and khassawneh et al . ,\nhowever , in asian adults , it was found that the prevalence of snoring is higher than the western population study .\nnevertheless , it should be understood that the prevalence of snoring does not necessarily indicate the development of obstructive complications but these findings do highlight the need for awareness about possible complications .\nthe results of this current study , indicate the nc is significantly greater for the snoring group than for the nonsnorer group .\nthis finding supports the view that nc is one of the significant risk factors for yemeni snorer , which is in good agreement with findings obtained in the chinese and japanese populations . increased nc even in the absence of obesity in our subjects ,\nmay draw our attention on the importance of the fat tissue around the neck in nonobese individuals . furthermore , snoring and greater nc were also considered as useful clinical predictors of osa .\nclinical examination findings indicate that the most frequent finding among snorer groups were straight profiles ( 52.0% ) , class i malocclusion ( 74.7% ) , and v palatal shape ( 16.0% ) , respectively .\neven though , there is no relationship between upper airway obstruction and the type of malocclusion were found but it has been reported that the upper pharyngeal width in the subjects with class i and class ii malocclusions with the vertical growth patterns were significantly narrower than in the normal growth pattern group .\ntherefore , this makes the orthodontist more alert to enquire about snoring even in class i malocclusion and straight profile patients especially with vertical growth patterns . on the other hand\n, it has been reported that convex profiles ( 71.7% ) , class ii malocclusion ( 51.7% ) , and v palatal shape ( 53.3% ) were frequent features in an asian osa sample .\nthis in contrast to our current study , and this could be related to the difference between the osa as a general term while the snoring is one of the osa symptoms and to the differences in the cranial base morphology between asians and caucasian . using dental examination\n, we found statistically significant difference between yemeni snorers and nonsnorer in a v - shape palatal arch ; the arch length and the inter- first premolar distance . in view of the fact that the roof of the mouth is also the floor of the nose , a narrow arch can infringe on the nasal cavity space\ntherefore , maxillary constriction , in addition to his responsibility as one of the important factors for determining nasal airway properties , it can also contribute to lateral narrowing of the upper oral cavity and a low tongue posture which consequently narrow the retroglossal region .\nthis may provide a reasonable explanation for the narrowing of the posterior airway space seen in osa patients . the v palatal shape was also included as one predictive morphometric model for osa , and the model illustrates the potential value of physical and dental examination .\nfor instance , there is a possibility of under diagnosis of snoring when a standard full night polysomnography test is not administered .\nhowever , berlin questionnaire can still be considered as an effective and inexpensive way for screening snoring .\nanother limitation of this study is the fact that females were not included . for cultural factors\n, this study suggests that snoring among our university population is associated with increased nc ; v - shape palatal morphology ; the short upper arch length ; and narrow inter- first upper premolar distance .\nclinically , increased nc even in the absence of obesity may draw our attention to the importance of the fat tissue around the neck in nonobese individuals .\nin addition , the orthodontist and other health care should be more alert to enquire about snoring , take the complaint of snoring seriously , and perform a thorough clinical and orthodontic evaluation even in class i malocclusion and straight profile patient especially college - aged male adult with vertical growth patterns .\nfurthermore , on the basis of clinical and orthodontic observation that have been recognized in this study , we believe that those observation features could be used to improve our understanding of the influence of snoring on the surrounding dentofacial structures of the adult university population and may provide valuable screening information in the identification of patients with undiagnosed osa .\nfurther studies are needed to find other clinical and orthodontic features in a diverse university population with different ethnic and sex trends in regards to snoring patterns .\nis associated with v - shape palatal morphology , increased nc , and decrease in the upper arch length and inter- first upper premolar distance .", "answer": "objectives : the objectives of this study were to determine the prevalence of snoring in an adult male university population , and to test the null hypothesis that there is no difference in facial profile shape , malocclusion type , or palatal morphology among snorer and nonsnorer.materials and methods : berlin questionnaire was given to 840 students and employees aged 1845 years ( 24 40 ) . both snorers and nonsnorers were assessed for the facial profile type , malocclusion type , and palatal morphology . \n chi - square and student 's t - test were used to compare the difference between the two groups.results:the prevalence of snoring was 16.28% . \n the most frequent findings among snorer were straight profiles ( 52.0% ) , class i malocclusion ( 74.7% ) , and v palatal shape ( 16.0% ) , respectively . \n the chi - square test revealed a significant difference in terms of v - shaped palatal morphology ( p < 0.05 ) ; higher neck circumference ( nc ) ( p < 0.007 ) ; upper arch length was significantly shorter ( p < 0.038 ) ; and the inter- first upper premolar distance was significantly narrower ( p < 0.013).conclusion : the null hypothesis is rejected . \n snoring in our university population is associated with v - shape palatal morphology , increased nc and decrease in the upper arch length , and inter- first upper premolar distance .", "id": 20} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto ensure successful pain relief , in - depth knowledge of local anesthetic solutions and appropriate application of local anesthetic techniques is mandatory .\nthe inferior alveolar nerve block is the most frequently used nerve block technique for anesthetizing mandibular teeth during endodontic procedures . in case of symptomatic irreversible pulpitis\nthe success rate of mandibular anesthesia with the inferior alveolar nerve block has been reported to vary from 38 - 85% .\nprevious studies have shown success rates of only 19 - 56% for inferior alveolar nerve blocks in patients with irreversible pulpitis .\nit is evident from these studies that severely painful inflamed tooth is often difficult to manage conventionally and local anesthetic failure is a common occurrence .\nthese include periodontal ligament injection , intrapulpal injection , intraosseous injection , and intraseptal injection .\nsupplemental injections are essential in patients with irreversible pulpitis as the local anesthetic injections had an eight - fold higher failure rate compared to normal patients .\nneedleless device uses pressure to force the anesthetic solution safely into oral tissues . in needleless jet injection ,\nthe anesthetic solution is immediately taken up by the myelin sheath of the nerve with an onset of action of approximately 1 ms .\nthe x - tip intraosseous injection allows deposition of a local anesthetic solution directly into the cancellous bone adjacent to the tooth to be anesthetized .\nsuccess of these supplemental intraosseous injections in achieving pulpal anesthesia in patients with irreversible pulpitis has been reported to be 82 - 98% .\nthe intraosseous systems available commercially in the market include the stabident system ( fairfax dental inc . ,\nmiami ) , x - tip system ( x - tip technologies , dentsply , maillefer ) , intraflow ( intra vantage , plymouth , mn ) , and the quicksleeper ( dht , cholet , france ) .\nclinical trial studies have been published using stabident , x - tip sytem , intra flow , and the quicksleeper system .\nthe x - tip anesthesia delivery system consists of a special hollow needle that serves as the drill and guide - sleeve component .\nthe drill leads the guide sleeve through the cortical plate after which it is separated and withdrawn .\nthe guide sleeve remains embedded in the bone and the anesthetic solution is delivered with the aid of a 27-gauge needle .\nthere has been a continual search for safer and more profound local anesthetic compounds for attaining adequate pulpal anesthesia .\narticaine , classified as an amide anesthetic , has increased liposolubility and potency because of the presence of a thiophene ring .\ngreater diffusion of articaine anesthetic solution to the teeth can be attributed to increased liposolubility and smaller size of thiophene ring of articaine in contrast to benzene ring of lignocaine . according to some authors ,\nability of articaine to diffuse into the bone can produce pulpal anesthesia in mandibular teeth even after infiltration anesthesia .\nclinical studies comparing the success rate of 4% articaine with that of 2% lignocaine have shown that 4% articaine was superior to 2% lignocaine as a general - purpose anesthetic .\nthe purpose of the study was to evaluate the anesthetic efficacy of x - tip intraosseous injection in patients with symptomatic irreversible pulpitis in mandibular posterior teeth , using 4% articaine with 1:100,000 adrenaline as local anesthetic when the conventional inferior alveolar nerve block proved ineffective .\nthe purpose of the study was to evaluate the anesthetic efficacy of x - tip intraosseous injection in patients with symptomatic irreversible pulpitis in mandibular posterior teeth , using 4% articaine with 1:100,000 adrenaline as local anesthetic when the conventional inferior alveolar nerve block proved ineffective .\nthirty patients , 15 males and 15 females 15 - 53 years of age with a diagnosis of symptomatic irreversible pulpitis of mandibular posterior teeth were included in this study .\napproval for the study was obtained from institutional ethical committee and written informed consent was acquired from each patient .\nthe diagnosis of irreversible pulpitis was confirmed by a chief complaint of spontaneous pain or pain at night , together with cold test and electric pulp testing showing an elevated and lingering pain response .\nvitality of these teeth was first tested with cold pulp tester , dichlorodifluoromethane ( endo - frost , roeko , langenau , germany ) followed by electric pulp tester ( digitest pulp tester ) . in all 30 patients selected , control teeth showed normal response and the inflamed teeth showed an elevated and prolonged pain response to these tests .\ninferior alveolar nerve block injection was administered using 1.7 ml of 4% articaine with 1:100,000 adrenaline ( septanest with adrenaline 1:100,000 , septodont , france ) with conventional long buccal injection . before commencing access preparation\n, it was ensured that the control teeth did not respond to the maximum output of the electric pulp tester and the cold test .\nthe patients were instructed to rate any discomfort during access using a heft - parker visual analogue scale ( vas ) [ figure 1 ] . the vas scale consists of four categories .\nmild pain was defined as greater than 0 mm and less than or equal to 54 mm .\nsupplemental intraosseous x - tip injection was administered in patients who had moderate or severe pain ( vas rating greater than 54 mm ) on access into dentin , when entering the pulp chamber or with initial file insertion .\nheft - parker vas pain scale used for pain assessment the intraosseous injection with the x - tip system ( dentsply maillefer , usa ) was administered in the following manner : the perforation site was selected according to manufacturer 's instructions , 2 - 4 mm apical to alveolar crestal bone level in the attached gingiva , at a site distal or mesial to the operating tooth .\nafter determination of the perforation site , the perforator attached in micromotor handpiece was pushed through the attached gingiva until the x - tip contacted bone . after placing the drill at a 90 angle to the bone , the slow - speed air motor handpiece was activated and drilled at 90 to the bone . in 2 - 4 seconds , the drill perforated the cortical bone into the cancellous bone .\nthe handpiece was always activated while the perforator was within the bone to prevent breakage that might occur if the perforator was allowed to stop rotating .\nafter perforation , the drill was withdrawn from the guide sleeve , leaving the guide sleeve in place .\nthe 27-gauge ultrashort x - tip needle was inserted into the guide sleeve to its hub , and 1.7 ml of 4% articaine with 1:100,000 adrenaline ( septanest with adrenaline 1:100,000 , septodont , france ) was delivered over a 1-minute time period .\nthe success of the supplemental x - tip technique is defined as the ability to access the pulp chamber , place initial files , and instrument the tooth without pain ( vas score of zero ) or mild pain ( vas rating less than or equal to 54 mm ) .\nif the patient had moderate to severe pain ( vas rating greater than 54 mm ) during access or initial instrumentation , the x - tip technique was considered as a failure and an intrapulpal injection was administered .\nout of the 30 patients who participated in the study , 25 patients experienced no pain or mild pain and were counted as success .\nfive patients who experienced moderate to severe pain during access or initial instrumentation after intraosseous injections were considered a failure .\nthe various factors associated with anesthetic failure for conventional ian block include accessory innervations , accuracy of needle placement , anesthetic solution migration along the path of least resistance , tetrodotoxin - resistant class of sodium channels , which have been shown to be resistant to the action of local anesthetics , anxiety , psychological factors , and altered resting potentials and decreased excitability thresholds of nerves arising from inflamed tissue . owing to these myriad limiting factors , supplemental injections become necessary in cases when inferior alveolar nerve block is not effective in providing satisfactory anesthesia . in needle - phobic patients ,\nthe time of onset of action for pressure anesthesia was less when compared to classic needle infiltration but the total duration of anesthesia was more for needle infiltration anesthesia . it can be used for restorative procedures of short duration and direct pulp injections . in this study , the anesthetic success using x - tip intraosseous injection was 83.33% .\nthe results of this study shows that supplemental x - tip intraosseous injection helps in achieving successful pulpal anesthesia in patients with symptomatic irreversible pulpitis .\nnone of the x - tip perforators broke , and the onset of anesthesia was immediate .\nthe thickness of the cortical plate of posterior mandibular region condemns the use of infiltration injections .\nthe intraosseous injection overcomes this problem by allowing direct access to the cancellous bone via perforation of the cortical bone . in this study ,\nthis fact is critical , as higher the lipid solubility , the higher is the potency and better will be the diffusion through the medium into which it is injected , and therefore , the greater is its ability to cross the lipid membranes of the epineuria\nthis molecular configuration is subject to rapid hydrolysis by plasma cholinesterases after it is absorbed into the systemic circulation .\nonly the remaining 5 - 10% is subject to the slower , traditional hepatic metabolism .\nthe allergen paraminobenzoic acid ( paba ) , a frequent metabolite of ester metabolism , is not a by - product of the hydrolysis phase of articaine .\nwithin the limitations of this study , we can conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia , the x - tip system using 4% articaine , was successful in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis .\nsupplemental intraosseous injection with x - tip using 4% articaine with 1:100,000 adrenaline enabled soothing , swift , and sound anesthesia .", "answer": "introduction : pain management remains the utmost important qualifying criteria in minimizing patient agony and establishing a strong dentist patient rapport . \n symptomatic irreversible pulpitis is a painful condition necessitating immediate attention and supplemental anesthetic techniques are often resorted to in addition to conventional inferior alveolar nerve block.aim:the purpose of the study was to evaluate the anesthetic efficacy of x - tip intraosseous injection in patients with symptomatic irreversible pulpitis , in mandibular posterior teeth , using 4% articaine with 1:100,000 adrenaline as local anesthetic , when the conventional inferior alveolar nerve block proved ineffective.materials and methods : x - tip system was used to administer 1.7 ml of 4% articaine with 1:100,000 adrenaline in 30 patients diagnosed with irreversible pulpitis of mandibular posterior teeth with moderate to severe pain on endodontic access after administration of an inferior alveolar nerve block.results:the results of the study showed that 25 x - tip injections ( 83.33% ) were successful and 5 x - tip injections ( 16.66% ) were unsuccessful.conclusion:when the inferior alveolar nerve block fails to provide adequate pulpal anesthesia , x - tip system using 4% articaine with 1:100,000 adrenaline was successful in achieving pulpal anesthesia in patients with irreversible pulpitis .", "id": 21} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntetralogy of fallot ( tof ) accounts for approximately 5% to 7% of all cases of congenital heart disease .\ncomplications related to surgical repair of tof are clinically relevant and include pulmonary regurgitation , residual obstruction of the right ventricular ( rv ) outflow tract , rv systolic dysfunction , and arrhythmias . among these ,\nresidual rv outflow tract obstruction with accompanying pulmonary regurgitation is the most frequently reported sequela after initial surgical correction of tof .\ntherefore , a systolic murmur that is audible over the base of the heart is frequently interpreted as a residual rv outflow tract lesion . however , this is not always true .\nwe herein report a rare case of subaortic stenosis in association with a previous tof surgical repair that was not considered to be a differential diagnosis .\ndiscrete subaortic stenosis is generally thought of as a disease of children or young adults ( < 25 years of age ) and is thus rarely reported in subjects older than 25 years , particularly in association with tof .\na 29-year - old woman presented for a routine check - up of surgically corrected congenital heart disease . at 7 years of age , she had undergone surgical repair of tof with excision of the infundibular stenosis and closure of a 10-mm ventricular septal defect .\nshe had been asymptomatic until her first decade of life , and only a 5-year clinical follow - up had been performed after the operation . approximately 6 months prior to presentation , she began to feel exertional dyspnea that was progressively aggravated . on physical examination , she was alert and well - oriented .\nher blood pressure was 100/60 mmhg , pulse 60 beats / min , respiration rate 18/min , and body temperature 36.6. the left ventricular ( lv ) impulse was almost normal in location .\non auscultation , a grade 3 of 6 mid- to late - systolic murmur was audible over the base of the heart and heard clearly on both sides of the sternum .\nroutine blood examinations , including a complete blood count , chemistry panel , coagulation panel , and c - reactive protein level , were all within normal ranges .\ntransthoracic and transesophageal echocardiograms both demonstrated severe subaortic stenosis due to a subvalvular membrane , on which a mobile mass - like structure that was suspicious of a vegetation was noted ( fig .\nthere was a mild degree of tricuspid regurgitation , but no clinically significant obstruction of the rv outflow tract .\nthe maximum velocity measured across the tricuspid valve was 2.8 m / sec , and thus the maximal pressure gradient was estimated to be 31.4 mmhg using the simplified bernoulli equation . due to the up to 20 mmhg pressure gradient across the pulmonary valve\nher rv was not dilated , and its systolic function was good . due to the suspicion of infective endocarditis despite the absence of clinical evidence , blood cultures were performed three times ; however , no pathogen was cultured .\nthe patient underwent resection of the subaortic membrane and myomectomy of the lv outflow tract along with aortic valve commissurotomy .\nthe membrane , with the exception of the noncoronary cusp area , was located beneath the aortic annulus ( i.e. , inverted u shape ) .\nthe mobile mass - like structure described on transesophageal echocardiography was proven to be loose tissue attached to the subaortic membrane .\nalthough subaortic stenosis is the second most - common form of lv outflow tract obstruction , it is predominantly found in children or adolescents [ 4 - 8 ] .\nsubaortic stenosis is strongly associated with other congenital heart defects ; however , subaortic stenosis in association with tof , especially in women , is extremely rare . according to a medline database review of the last 30 years\nfurthermore , all were diagnosed in childhood or adolescence ( < 20 years of age ) with two exceptions .\nthe present case is peculiar in that subaortic stenosis manifested more than 20 years after the initial tof surgical correction .\nalthough we could not definitively say that the subaortic stenosis in the present case was acquired , we consider it an acquired or progressive form given the long interval ( > 20 years ) before echocardiographic confirmation .\nthomas and foster suggested that acquired subaortic stenosis can develop gradually due to hemodynamic disturbances derived from coexisting lesions or after surgical correction .\nmoreover , the mass - like mobile structure observed on transesophageal echocardiography could be regarded as a degenerative byproduct of flow convergence induced by the subaortic membrane , further supporting the concept of an acquired or progressive form of the disease .\ndiscrete subaortic stenosis is well - known to be linked to important complications , such as bacterial endocarditis and significant aortic regurgitation .\nflow turbulence distal to the obstructing subaortic membrane plays a crucial role in progressive damage to the aortic valve with resultant thickening of its leaflets and regurgitation .\nthe secondary jet lesion also predisposes the patient to bacterial endocarditis . in this context ,\nin particular , patients with surgically corrected tof tend to be misinterpreted as having only residual rv outflow obstruction without consideration of the lv outflow tract lesion .\ntransthoracic and transesophageal echocardiography can assist differentiation of the rv from the lv outflow tract obstruction .\ntherefore , periodic performance of echocardiography should be kept in mind during follow - up of patients with surgically corrected tof .", "answer": "we herein report a rare case of subaortic stenosis in association with a previous tetralogy of fallot ( tof ) surgical repair , which was not taken into account as a differential diagnosis . \n echocardiography plays a pivotal role in identification of this rare combination . \n therefore , echocardiography should be performed periodically during follow - up of patients with surgically corrected tof . \n given the clinical complications that can result from subaortic stenosis ( i.e. , aortic regurgitation and infective endocarditis ) , early and aggressive management of this rare combination should be performed .", "id": 22} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin our model , each particle consists of a core sphere with four tetrahedrally oriented arms ( see fig .\nthe central sphere and the arms are modeled as interpenetrating hard spheres with diameter , with the centre of each arm located a distance l from the centre of the core . on the surface of each arm\nthe patch is modeled , via a standard kern - frenkel potential , as a square - well type attraction of depth : two particles are either bound or unbound , with no intermediate energy levels .\nthe opening angle of the patch is given by cos = 0.95 , and the maximum interaction range = 0.251. this choice ensures that each patch can form a bond with only a single other patch .\nfurthermore , in order to model arm flexibility , each arm can freely rotate around the core sphere within a maximum angle from its ideal ( tetrahedral ) position .\nnote that there are no hard - core interactions within a particle : spheres belonging to the same tetramer can overlap .\neach mc simulation included translation moves , rotation moves rotating a full tetramer , rotation moves rotating only the core sphere , and rotation moves that rotate a single arm around the core . additionally , we added volume moves for isobaric simulations , and particle insertion and deletion moves for grand - canonical successive umbrella sampling ( sus ) simulations . to detect ll phase separation , we used sus simulations , generating the relative free energy as a function of the density . to calculate the phase diagrams in fig . 4 , and the crystallization lines in figs . 2 and 3\nfor the liquid phases , we used a high temperature fluid as a reference state , where we obtained the helmholtz free energy f by combining the chemical potential ( evaluated from a sus simulation ) and the pressure p at the same density ( taken from an npt mc simulation ) , using : \n ( 1)ffn=p , \n where n is the number of particles .\nwe then used thermodynamic integration by integrating the temperature along an isochore : \n ( 2)2f(,t2)=1f(,t1)+12du(,t ) , \n with u( , t ) the average potential energy per particle , = 1/kbt and kb boltzmann s constant .\ntypically , at sufficiently low temperatures , the energy as a function of temperature takes the form \n ( 3)u=2+cexp(2 ) , \n where 2 is the ground - state energy ( where each particle has four bonds ) and c is a ( density - dependent ) constant .\nthis allows for straightforward extrapolation of the free energies to arbitrarily low temperatures after the regime in eq .\nthis regime is accessible in our simulations for all cases where the fluid does not crystallize at low t ( i.e. cos 0.9 ) . system sizes for the sus simulations\nwere chosen such that near the ll transition the system contained n 150 particles .\nother free - energy calculations were performed with similar or larger n. the investigated crystal structures were diamond and bcc ( corresponding to ice ic and ice vii in water , respectively ) . both are fully bonded structures and as such have the ( same ) lowest possible potential energy . depending on cos and l , there will be a variety of other fully bonded crystal structures .\nhowever , the structures commensurate with an ideal tetrahedral geometry will always have the highest entropy and hence will be more stable at the densities where they are accessible .\nthus , the only crystals which might compete with the ll phase separation are diamond and bcc . at high density ,\ni.e. beyond the bcc density , the stable crystalline phases will be controlled by a competition between packing , energy , and entropy , but as these phases will not change the stability of the ll phase transition , they are outside of the scope of this letter .\nsimilarly , we do not expect these crystal phases to affect the phase diagrams in fig .\n4 , with the possible exception of the ( dashed ) high - density liquid - bcc lines in panels ( c ) and ( d ) . to determine free energies for the crystal phases , we used an einstein crystal approach , for each t where a phase coexistence was calculated .\nsubsequently , using npt mc simulations , we employed thermodynamic integration along the density at constant temperature : \n ( 4)f(,t)=f(ref , t)+refd()p2 , \n where ref is the density where the reference free energy was calculated .\ns4 in the si for examples ) . to determine whether spontaneous crystallization occured in our sus simulations , we used a bond - order parameter to find the largest crystalline cluster in the system .\nfirst , we determine the neighbors of each particle using a solid - angle based nearest - neighbor method .\nwe then calculate for each particle the complex vector ql , the expansion of their environment in terms of spherical harmonics ylm , with l\nthe order of the symmetry of the crystal , and l m l : \n ( 5)qlm(i)=1nb(i)j=1nbylm(r^ij ) . \n here , nb is the number of neighbors of particle i , and r^ij is the normalized vector connecting particle i to particle j. for the purpose of finding crystalline clusters , two particles are considered bonded when their environments are sufficiently similar . to determine this , we calculate : \n ( 6)dl(i , j)=re(ql(i)ql(j)ql(i)ql(j) ) . \n to detect bcc clusters , we choose l = 6 , consider two particles bonded if dl(i , j ) > 0.6 , and label any particle that has at least 5 bonds as a crystalline particle . for diamond , two particles\nare considered bonded if either dl(i , j ) < 0.87 or 0.3 < dl(i , j ) < 0.1 , and only particles with 4 bonds are considered crystalline .\nsystems were considered to have crystallized spontaneously when more than 10% of the system was crystalline .\nnote that although the q6 based order parameter is sensitive to multiple crystal structures , visual inspection of the detected clusters consistently showed a bcc structure in all cases .", "answer": "one of the most controversial hypotheses for explaining the origin of the thermodynamic anomalies characterizing liquid water postulates the presence of a metastable second - order liquid - liquid critical point [ 1 ] located in the no - man s land [ 2 ] . in this scenario , \n two liquids with distinct local structure emerge near the critical temperature . unfortunately , since spontaneous crystallization is rapid in this region , experimental support for this hypothesis relies on significant extrapolations , either from the metastable liquid or from amorphous solid water [ 3 , 4 ] . \n although the liquid - liquid transition is expected to feature in many tetrahedrally coordinated liquids , including silicon [ 5 ] , carbon [ 6 ] and silica , even numerical studies of atomic and molecular models have been unable to conclusively prove the existence of this transition . \n here we provide such evidence for a model in which it is possible to continuously tune the softness of the interparticle interaction and the flexibility of the bonds , the key ingredients controlling the existence of the critical point . \n we show that conditions exist where the full coexistence is thermodynamically stable with respect to crystallization . \n our work offers a basis for designing colloidal analogues of water exhibiting liquid - liquid transitions in equilibrium , opening the way for experimental confirmation of the original hypothesis .", "id": 23} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients with conditions such as psoriasis , eczema , and skin cancer frequently face psychologic challenges which , in turn , impact their social functioning and the kind of life that they lead .\npatients may experience fearful anticipation of interaction with others , even when symptoms are not present , and develop avoidance - coping mechanisms .\nthis may prevent them from partaking fully , or at all , in social and recreational activities or employment .\nultimately , visible symptoms may change how patients see themselves and how they perceive their future .\nmultiple studies reveal consistently poorer quality of life and psychosocial functioning scores among patients with visible dermatologic skin conditions compared with those who do not have such conditions [ 25 ] .\nthe incidence of psychosocial comorbidities among such patients is high , as evidenced by a study which found that the risks of depression , anxiety , and suicidality attributable to psoriasis were 11.8 , 8.1 , and 0.4 per 1000 person years , respectively ( table 1 ) .table 1the attributable risk of psoriasis for diagnosis with depression , anxiety , and suicidality mild psoriasissevere psoriasisall psoriasisdepression attributable risk per 1000 person - years11.525.511.8anxiety attributable risk per 1000 person - years8.08.18.1suicidality attributable risk per 1000 person - years0.40.40.4reproduced with permission from arch dermatol .\nall rights reserved \n adjusted for age and sex \n the attributable risk of psoriasis for diagnosis with depression , anxiety , and suicidality reproduced with permission from arch dermatol\nall rights reserved \n adjusted for age and sex the dermatologist can play an important role in helping patients to overcome such substantial challenges and improve their overall quality of life .\nwe discuss several important considerations and propose strategies to assist dermatologists in addressing the important psychosocial side of treatment in patients with visible skin conditions .\nstudies have shown that successful treatment , which improves the patient s symptoms and changes their physical appearance , can lead to improvement in psychologic symptoms and a better quality of life [ 2 , 6 ] . however ,\nit is important to note that , sometimes , greater life satisfaction is achieved by accepting that perhaps some symptoms will remain or recur , even if a patient generally responds well to treatment .\nsuch acceptance involves acknowledging the existence of symptoms , but frees up the patient to pursue a meaningful life that is not overly limited by their condition .\nit is also crucial that patients are provided with the tools to accept their remaining symptoms and to reduce the impact of these on everyday life .\nas a clinician , one is familiar with the broad spectrum of available treatment options and the tools used to objectively measure outcomes in a clinical and/or academic setting .\ntreatment may be deemed successful if improvements in physical symptoms are in line with the results one would typically observe in other patients , or those that have been reported in clinical trials .\nhowever , it is important to remember that other factors may influence the patient s own perception of treatment success .\npatients have their own preferences and priorities regarding what treatment outcomes are more important to them .\nfor example , one patient may favor reduction or elimination of signs of disease that are visible to others when wearing typical clothes ( which may change with the season ) , whereas another patient may be more interested in reducing their level of physical discomfort .\npatients satisfaction is strongly influenced by their initial expectations and the changes they were expecting to see , as well as those of their family and friends ; objective measures of symptom improvement may be less important to them . therefore , when evaluating treatment options , it is important to consider asking the patient what outcomes are most important to them and to discuss what it is reasonably possible to achieve .\nas such , a broad outcome measure that includes psychosocial and overall quality of life measures , in addition to symptom remission , would be of particular value .\n, clinicians may wish to discuss expected outcomes before treatment is initiated , including the degree of symptom improvement that can realistically be expected , the likelihood of success , and the timescales involved .\nthis would ideally be a two - way conversation , in which the clinician could ask the patient to explain their hopes and expectations as a result of their treatment .\nthere are several ways in which realistic expectations ( i.e. not too high and not too low ) will result in the best outcome for the patient .\nif expectations are sufficiently high , a patient is more likely to be willing to initiate treatment and remain compliant , as they will be confident that they will eventually see an improvement in their symptoms .\nsimilarly , if they have a tempered understanding of the expected degree of improvement , and when this may occur , they will be more likely to adhere to treatment without getting discouraged by seemingly poor results .\nthis is especially important in the case of complicated regimens , such as those associated with frequent or inconvenient drug administration , those that involve some degree of pain or discomfort , or those in which extensive treatment is required before symptoms begin to improve .\nsecondly , appropriate expectations can help a patient and their family to know when they need to return to the clinician and ask for a different treatment approach .\nsuch a dynamic , interactive relationship between the clinician and the patient can ensure that the patient s needs are being met wherever possible , and may reduce unnecessary time and costs associated with treatment that is inappropriate or ineffective for that person . finally , focusing on the broad improvement of patient quality of life , and not just on the management of visible symptoms , may help to reduce the often excessive pressure placed on healthcare providers by patients with unrealistic expectations for improvement .\nthis can improve the clinician 's own sense of job satisfaction , as well as the overall relationship between the clinician and the patient .\nimpairment , however , is defined as the suffering that can be caused by symptoms , and may be physical , psychologic , and/or social .\nthe degree of impairment caused by a given symptom is often different in different people ; in fact , a patient can have a severe symptom but not be impaired by it at all .\nconversely , a different patient may be greatly impaired by symptoms of relatively mild severity , with a tremendously negative impact on their life .\nfor example , an insecure teenager may feel extremely self - conscious about minor acne and avoid some social situations , whereas a confident young adult with much worse symptoms may hardly think about them .\nwhen it comes to reducing the psychologic impact of a dermatologic condition and improving the patient s quality of life , it is crucial that we address impairment and not just symptoms .\nit is possible for a patient to actively refuse to be unnecessarily limited by their symptoms , rather than be passively resigned to them .\nhowever , support and encouragement are often needed in order for a patient to achieve this . as clinicians\n, we have the opportunity to encourage patients to live a big life , i.e. a life that is fulfilling , rewarding , meaningful , and interesting , and that has a positive impact on the world , in which the person accomplishes most of what they set out to do . in turn\n, the patient may strive to be the person that they want to be , regardless of their health status .\nother professionals , such as nurses , psychotherapists , or counsellors , who may be involved in the wider healthcare circle of a patient , can also assist in this regard . in some cases , an overly negative response to symptoms\ncan be indicative of low self - esteem , anxiety , or depression , which can warrant a referral to a mental health professional to help the patient cope , not only with their dermatologic condition , but also with other matters .\nwe can help patients to redefine themselves by asking the question , what would / could you do if you did not have these symptoms ? \nit should be emphasized that , although symptoms may affect how a patient lives their life , symptoms do not necessarily need to rule a patient s life .\nwe can also help patients to understand that tolerating discomfort may allow them to pursue more interesting goals in life .\nmental health professionals can help more limited patients to learn better coping methods to deal with sometimes debilitating discomfort .\npatients should , of course , be encouraged to follow the treatment regimen , and active engagement with the clinician will enable the patient to feel that they are in control of their condition and their treatment program .\nhowever , we can emphasize to patients that it is important not to wait for complete symptom remission before pursuing a fulfilled life .\nsome patients restrict their social engagement because they feel self - conscious about their visible symptoms and do not know how to respond to people s questions about them , such as why they look that way , or whether the condition is contagious .\nhelping patients find the right words to explain their visible symptoms to others can help them feel more comfortable going out into the world .\nthis is particularly true of situations in which the patient is likely to encounter people who are more likely to make inappropriate comments , ask personal questions , or make incorrect assumptions , such as that the condition is highly infectious .\nit is easier for the patient to cope and feel confident in such situations if they have an appropriate and informed range of responses prepared in advance .\npatients can choose to share personal information , but they also have the right not to do so .\nvisible medical conditions such as psoriasis , eczema , and skin cancer often have a substantial psychologic and social impact on patients .\nhowever , through appropriate discussion and interaction with a patient , the dermatologist can play an important role in helping to reduce this impact , potentially improving the patient s overall quality of life .\nit is important to discuss expected outcomes before treatment is initiated , in order to ensure that realistic expectations are in place . it may also be beneficial to discuss whether total symptom relief is a necessary component to living a better life . in addition ,\nhelping patients to find the right words to explain their visible symptoms to others can help them feel less self - conscious and more confident in a public setting . helping patients to come to terms with their condition , and helping them to build the skills required to reduce the psychosocial impact of their condition\n, may mean that they are more equipped to go out into the world and pursue a more meaningful life .\nthis article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors .", "answer": "skin conditions such as psoriasis , eczema , and skin cancer often have a substantial psychologic and social impact on our patients . \n some of these patients limit their life because they feel self - conscious about their symptoms . \n sometimes , greater life satisfaction comes from accepting that perhaps some symptoms will remain or recur , even in an individual who responds well to treatment . \n this acceptance involves acknowledging the existence of symptoms , thereby allowing the patient to pursue a meaningful life that is not overly limited by their potential presence . \n this is not only liberating for the patient but also for the medical professional , who can sometimes feel pressured by patients unrealistic expectations to achieve symptom reductions that are not possible . \n we discuss how to talk with patients about their expectations regarding treatment and whether relief of symptoms is a necessary component to living a better life . \n helping patients to find the right words to explain their visible symptoms to others can sometimes help them feel less self - conscious in public settings and thereby more comfortable going out into the world to pursue a meaningful life .", "id": 24} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfor the past 50 years disulfiram is the commonly prescribed drug for the treatment of alcohol dependence .\nimportant side effects of disulfiram are hepatological , dermatological , neurological ( polyneuritis , encephalopathy)1,2 ) and psychiatric in nature .\npsychiatric manifestations include confusion , loss of memory , psychosis,36 ) mania with psychotic symptoms.7,8 ) disulfiram s major metabolite diethyldithiocarbamate is an inhibitor of dopamine - betahydroxylase ( dbh ) , an enzyme that catalyzes the metabolism of dopamine ( da ) to norepinephrine ( ne).9 ) by inhibiting this metabolic pathway from da to ne in the central nervous system , disulfiram results in an increase of da concentrations in mesolimbic system resulting in psychosis .\nalcoholics who developed psychotic symptoms during disulfiram treatment are found to have low levels of amine and monoamine oxidase , suggesting dbh blockage.10 ) we present a case of 32-year - old male who developed psychosis with the use of disulfiram .\na 32-year - old male without past of psychiatric and neurological illness reported to psychiatry outpatient department with complaint of daily alcohol intake of 250750 ml ( 40% alcohol by volume ) for the last 5 years . with the informed consent of the patient\n, disulfiram was administered at the dosage of 250 mg twice daily for 1 month , while the patient abstained from alcohol .\nthen the patient presented complaint of fearfulness , suspiciousness , easy irritability , muttering to self , decreased sleep for last one month .\nhaematological and biochemical indices were within normal limits . on mental status examination delusion of persecution and auditory\nhis fearfulness , suspiciousness , irritability , muttering to self and impaired sleep gradually improved over a period of 10 days .\nrisk factors for development of disulfiram related psychotic symptoms include past history or family history of psychosis , overly rapid increase in dosage or greater than recommended total dosage , old age , impaired liver function and concurrent dopaminergic medications or psycho - stimulant abuse.5,11 ) our patient has family history of schizophrenia in his father .\nhis psychotic symptoms improved after stoppage of disulfiram and use of lorazepam tablet only without any additional requirement of anti - psychotic treatment .\nthese factors support the association between with disulfiram use and emergence of psychotic symptoms in our patient .\nthe usual recommended initial dosage is 500 mg per day for the first 1 or 2 weeks , followed by a maintenance dosage of 250 mg per day.12 ) disulfiram related psychosis usually involve either therapeutic or higher than recommended dosages.13 ) our patient has developed psychotic symptoms with 500 mg per day of disulfiram .\nwe recommend that disulfiram should be used at the lowest effective dose , possibly 250 mg daily .\nour case highlights the relevance of a careful history of patient s symptoms and family history that should be performed before starting treatment with disulfiram and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis .\ndisulfiram - related psychiatric complications are reported to be more prevalent in eastern countries,3 ) which suggests that genetic factors may play a role in disulfiram induced psychosis .", "answer": "disulfiram is the commonly prescribed drug for the treatment of alcohol dependence . \n it s major metabolite ( diethyldithiocarbamate ) is an inhibitor of dopamine - betahydroxylase , an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis . \n we recommend that disulfiram should be used at the lowest effective dose , possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis .", "id": 25} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe sign of leser - trelat historically has been characterized as the sudden eruption of numerous seborrheic keratoses and considered an ominous sign of internal malignancy , as it is classically described before the diagnosis of malignancy .\nthe seborrheic keratoses themselves are benign and , in some cases , have been reported to resolve with treatment of the underlying malignancy .\nthe mechanism of this phenomenon has been ascribed to secreted cytokines and growth factors from tumors ( e.g. , elevated epidermal growth factor receptor [ egf - r]-mediated signaling ) leading to development of seborrheic keratoses ( yamamoto , 2013 ) .\nthe malignancies classically implicated in the setting of sign of leser - trelat are gastric adenocarcinoma and other tumors of the digestive tract ; additionally , other classes of malignant tumors , such as lymphoma and breast cancers , have been cited in association with the condition ( husain et al . , 2013 ) .\nrare cases of gynecologic cancers ( e.g. , uterine leiomyosarcoma and ovarian adenocarcinoma ) have been associated with the sign of leser - trelat ( abakka et al .\n, 2013 , holguin et al . , 1986 ) . in general , with the exception of hypercalcemia and disseminated intravascular coagulation , paraneoplastic syndromes\nare not classically associated with gynecologic cancer ( ashour et al . , 1997 ) .\nthis case illustrates eruptive seborrheic keratoses with atypical annular and gyrate erythema that occurred in the setting of endometrial adenocarcinoma , which resolved upon surgical removal of the malignant uterine tissue ( lacey and chia , 2009 ) .\na 61-year - old post - menopausal caucasian female presented for an initial evaluation of numerous intensely pruritic scaly spots on her trunk .\nshe reported that similar lesions had been diagnosed as seborrheic keratoses by another dermatologist ; however , in the month before presentation in our clinic , the number of lesions on her trunk had dramatically increased .\nthe patient was able to distinguish new lesions from her existing seborrheic keratoses because they were constantly pruritic and many had coalescing and concentric rings of erythema around them .\nshe denied any history of cancer , but upon inquiry regarding her family history , she reported that her father had died of gastric cancer .\nthe patient denied any constitutional symptoms or any uterine bleeding , and complete review of symptoms was significant only for depression .\nher past medical history was significant for squamous cell carcinoma , uterine fibroids , dysmenorrhea , granuloma annulare ( ga ) , and benign pulmonary nodules .\ntotal body skin examination was notable for numerous brown papules that appeared to be attached to the surface of her skin as well as plaques consistent with inflamed seborrheic keratoses with surrounding annular and gyrate erythema with scaling at edges of rings some of which were concentric and had the appearance of targets on the face , neck , and trunk . there were no signs of acanthosis nigricans .\nbiopsy of an erythematous lesions surrounding a seborrheic keratosis on her trunk revealed multifocal intraepidermal langerhans cell microabscesses with eczematous dermatitis and superficial perivascular infiltrate containing scattered histiocytes and without granulomatous inflammation .\nthis presentation of atypical , acute eruption of seborrheic keratoses and family history of gastric cancer , as well as the fact the patient had not yet had her age - appropriate cancer screenings , prompted concern that the eruption was a marker of internal malignancy , and screenings for malignancy were recommended . she initially declined colonoscopy and other first - line screenings and insisted that she would only accept a positron emission tomography scan , which highlighted focal intense uptake in the uterus ; based on this , transvaginal ultrasound was recommended and revealed abnormally thickened endometrium .\ndilatation and curettage also revealed complex focal atypical hyperplasia , which prompted the gynecology team to perform a hysterectomy , and the postoperative diagnosis was endometrial adenocarcinoma . because of the significant , distressing pruritus associated with the lesions , the patient was treated symptomatically during the work - up period .\nsymptomatic treatment with cryotherapy , phototherapy , and topical steroids yielded some partial improvement ; however , the patient experienced dramatic clearance of the erythematous skin lesions and marked improvement in her pruritus after surgical removal of the abnormal uterine tissue . at present , after the hysterectomy , she has developed no new seborrheic keratoses and is asymptomatic .\nalthough seborrheic keratoses are a common benign skin finding in elderly people , a rapid and intensely pruritic eruption warrants suspicion for occult internal malignancy .\nspecial care should be taken for patients with first - degree relatives of gastric cancer because it is the most commonly implicated cancer in paraneoplastic dermatoses ( e.g. , the sign of leser - trelat ) .\nthe marked annular , gyrate , and targetoid erythema associated with seborrheic keratoses seen in our patient is not typical for the classic sign of leser - trelat .\nit is possible that this unusual morphology represents two coexistant paraneoplastic dermatoses similar to those seen in cases of prostate cancer and renal angiosarcoma ( da rosa et al . , 2009 , rubegni et al . , 2014 )\nthe possibility that the annular erythematous plaques could be a reactive granulomatous process was also considered , given the patient s history of ga . however , upon consultation with the pathologist , it was clarified that no granulomatous inflammation was seen .\nthe notable presence of high numbers of langerhans cells seen on microscopy may have signified abnormal antigen presentation in these lesions , which also supports a paraneoplastic process .\nit was suspected that cytokines and hormone stimuli associated with the endometrial adenocarcinoma might have triggered the paraneoplastic dermatosis . as in this patient 's case\nthis case demonstrates a common gynecological cancer presenting with a paraneoplastic dermatosis rather than the classical signs of uterine bleeding , and serves to raise awareness of cutaneous manifestations as markers of malignancy in a women s health issue in which early detection can affect health outcomes .\n-a sudden eruption of numerous seborrheic keratoses should prompt a malignancy work - up in patients with risk factors and those who have not undergone age - appropriate cancer screenings .- although gastric adenocarcinoma is the malignancy most commonly associated with the sign of leser - trelat , the possible association of other malignancies may necessitate a thorough work - up for internal malignancy . a sudden eruption of numerous seborrheic keratoses should prompt a malignancy work - up in patients with risk factors and those who have not undergone age - appropriate cancer screenings . although gastric adenocarcinoma is the malignancy most commonly associated with the sign of leser - trelat , the possible association of other malignancies may necessitate a thorough work - up for internal malignancy .", "answer": "eruptive seborrheic keratoses have been reported as a rare paraneoplastic dermatosis in the setting of internal malignancy , particularly that of the digestive tract . \n this case illustrates a patient with a family history of gastric cancer who presented with an acute eruption of inflamed pruritic seborrheic keratoses with annular and gyrate erythema , and was found to have endometrial adenocarcinoma . \n the inflammatory cutaneous eruption resolved shortly after surgical removal of the dysplastic uterine tissue . \n this case demonstrates an example of a common gynecological malignancy presenting in an uncommon way ; in the absence of uterine bleeding , the patient s skin manifestations in the form of a paraneoplastic dermatosis prompted timely diagnosis . \n thus this case serves to raise awareness of cutaneous manifestations of a women s health issue , in which early detection can impact health outcomes .", "id": 26} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe study protocol was approved by the ethics committee of the ministry of health and the school boards .\na total number of 30 clusters including 7,493 girls ( aged 620 years ) were selected .\nstudents with a history of acute or chronic diseases or any chronic medication use were excluded . in all subjects , height , weight , and pubertal stages\ngeneral physicians determined pubertal stages under the supervision of specialists by visual inspection and palpation , using the criteria and definitions described by marshall and tanner.10 accordingly , breast stages 15 were determined by both inspection and palpation .\nbreast stage b2 corresponded to the breast bud stage with palpable glandular breast tissue and elevation of the papilla , stage b3 with further enlargement of the breast and areola with no separation of the contours , stage b4 where the areola and papilla form a secondary mound above the level of the breast , and stage b5 was assigned in case of the mature breast with projection of the papilla only .\nthe onset of puberty was measured as the age at breast development at tanner stage 2 ( b2 ) .\nstage ph2 was assigned with the presence of long , slightly pigmented hair ( straight or curled ) .\nparticipants were grouped by 1-year age intervals , which extended from the day of their birthday to the day before the next birthday . for comparison of different areas\n, we used the national classification of the provinces according to their climate , ethnicity of the population , geographic locations , and socioeconomic variables .\nclassification of iranian provinces to regions according to climate , geographic location , ethnicity and socioeconomic status we estimated the mean of the time of men - arche , b2-b5 and ph2-ph5 stages .\nstatistical analysis was done using spss version 15 ( spss , chicago , il ) .\nanalysis of variance ( anova ) and post - hoc tests were used to compare the mean ages of menarche , pubarche , and telarche in different regions .\nwe estimated the mean of the time of men - arche , b2-b5 and ph2-ph5 stages .\nstatistical analysis was done using spss version 15 ( spss , chicago , il ) .\nanalysis of variance ( anova ) and post - hoc tests were used to compare the mean ages of menarche , pubarche , and telarche in different regions .\nwe estimated the mean of the time of men - arche , b2-b5 and ph2-ph5 stages .\nstatistical analysis was done using spss version 15 ( spss , chicago , il ) .\nanalysis of variance ( anova ) and post - hoc tests were used to compare the mean ages of menarche , pubarche , and telarche in different regions .\ntehran had the lowest mean age of menarche , being 11.99 1.35 years , which was significantly lower than other 10 regions .\nthe second region with lowest age at menarche was fars ( 12.40 1.27 years ) .\nthe mean age at b2 stage of breast development was significantly lower in ghazvin - zanjan region ( 8.97 1.45 years ) followed by the region consisting of khorasan jonobi and sistan balochestan ( 10.11 1.61 years ; p = 0.003 ) , boshehr - khouzestan region ( 10.05 1.21 years ; p = 0.01 ) , tehran - relatd cities ( 10.46 1.67 years ; p < 0.0001 ) , fars ( 11.01 1.88 years ; p < 0.0001 ) and kordestan - lorestan - ilam region ( 9.94 1.25 years ; p = 0.02 ) . in fars region , the mean age at b2 stage of breast development ( 11.01 1.88 years ) was higher than other regions except for mazendran - guilan and tehran - related cities regions .\nfigure 2 shows the mean age at b1-b5 of breast development in different regions in iran .\nmean age ( years ) at menarche in different regions mean age ( years ) at various stages of telarche in different regions in iran the mean age at ph2 stage of pubarche in kordestan - lorestan - ilam region ( 10.70 1.23 years ) was significantly higher than khorasan jonobi - sistan balochestan region ( p < 0.0001 ) , boshehr - khozestan region ( p < 0.0001 ) , tehran - relatd cities ( p < 0.0001 ) , chaharmahal - kerman - isfahan region ( p < 0.0001 ) , ghazvin - zanjan region ( p < 0.0001 ) , and boshehr - khozestan region ( p < 0.0001 ) .\nthe mean age at ph2-ph5 of pubic hair development in different geographic locations of iran is presented in figure 3 .\nto the best of our knowledge , this is the first study of its kind to compare the pubertal stages in different geographic locations in a country .\nit should be acknowledged that such comparison is not feasible in many countries with small population and no significant diversity in climate and other geographic characteristics .\nwe found that the mean age of menarche was significantly lower in tehran than all other regions .\ntehran province , including the metropolitan city of tehran , is located in central part of the country with multiethnic population .\nnot only multi - ethnicity but also higher socioeconomic status and more industrialized lifestyle habits in tehran might be associated with earlier menarche age . in another study\nthe mean age of menarche was 12.68 years in tehran in 2004.11 in our study conducted 2 years later , this age decreased to 11.99 1.35 years . decreasing trend of menarche age\nis observed in many developed and developing countries.1213 it might be attributed to changes in socioeconomic status of people14 and increasing rate of obesity.12 ethnicity is documented as a factor that describes some international varieties of puberty age.1516 in the current study , the mean age at menarche and ph2 was higher in girls with kurd ethnicity than in other ethnicities .\nkurd ethnicity is the third most prevalent ethnicity in iran after persian and azeri ethnicities .\nit can be suggested that the higher age of puberty in girls of this region might be attributed to their ethnicity as well as the cold climate and their high altitude mountainous region of living .\nin addition to ethnicity , the geographic characteristics may influence the age of puberty . in our study , the lowest mean age at b2\nwas documented in zanjan - ghazvin region , with mediterranean weather and spring rains , and population of azeri ethnicity .\nthe earlier telarche in this region in comparison to other regions with azeri population might be attributed to environmental factors .\npremature telarche is suggested to be associated with endocrine disrupting chemicals found in pesticides and plastics , with possible estrogenic and androgenic activities.1718 further investigations on environmental pollution might be necessary in this regard .\nthe considerably high prevalence of overweight among young iranian children19 might decrease the age of puberty in the near future .\nthe main limitation of this study was its cross sectional nature , and as a result , casualty can not be ascertained .\nin addition , we considered the prominent ethnicity in each region ; but some participants might have other ethnicities .\nwe found significant differences in the age of pubertal stages of girls living in various regions with different ethnicity and geographic characteristics .\nconsidering the impact of pubertal age on general health , more studies should be done about the lifestyle and environmental factors affecting the onset of puberty .\nmem participated in the design and conducting the study ; ar participated in the design and conducting the study and helped to draft the manuscript ; rk drafted and edited the manuscript ; pm conducted the statistical analyses and helped to draft the manuscript ; ss participated in conducting the study ; ga participated in the design and conducting the study ; ha participated in conducting the study ; np participated in conducting the study ; sk in conducting the study ; pp helped to draft and edit the manuscript ; as participated in conducting the study .", "answer": "background : this study aimed to compare the timing of puberty between various geographic locations and different ethnicities.methods:this national survey was conducted in 20 provinces in iran . \n healthy iranian girls were selected from public schools using cluster random sampling . \n a total number of 30 clusters including 7493 girls , aged 6.020 years , were selected . in order to compare different areas , the national classification of the provinces based on climate , ethnicity , geographic locations , and socioeconomic variables were used . \n accordingly , there are 11 regions in iran . \n analysis of variance was used to compare the mean ages of menarche , pubarche , and thelarche in different regions.results:tehranian girls , with 11.99 1.35 years ( mean sd ) , had the lowest age of menarche which was statistically significantly . \n the second region with lowest age at menarche was fars ( 12.40 1.27 years ) . \n the mean age at breast bud stage ( b2 ) was significantly lower in ghazvin - zanjan region ( 8.97 1.45 years ) . in fars region , \n the mean age at b2 stage of breast development ( 11.01 1.88 years ) was higher than other regions except for mazendran - guilan and tehran - related cities . \n the mean age at public hair development at tanner stage 2 ( ph2 ) in kordestan - lorestan - ilam region ( 10.70 1.23 years ) was significantly higher than other regions.conclusions:we found significant differences in the age of pubertal stages of girls living in various regions with different ethnicity and geographic characteristics . \n considering the impact of pubertal age on general health , more studies should be done about the lifestyle and environmental factors affecting the onset of puberty .", "id": 27} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nusing water as solvent in the organic reactions is one of the most important targets to organic chemists because of the easy availability , nontoxicity , and ecofriendly nature of the water [ 17 ] . in this endeavour\n, a number of chemical reactions such as diels alder , hetero diels - alder , 1,3-dipolar cycloaddition , oxidations , reductions , and others are performed successfully in water [ 13 ] .\nalso , it is reported that in few cases addition of the water increases the rate and the yield of a reaction and also enhances the enantioselectivity in a chiral synthesis .\nbut the main problems associated with water as a solvent is its poor ability to solubilise organic reactants and incapability to create anhydrous condition for moisture sensitive organic compounds and catalysts . to overcome the solubility problem , generally a surfactant is introduced to the reaction mixture .\nthe surfactant , due to its hydrophobic and hydrophilic nature , forms micelles with water insoluble organic compounds and promote the desired reactions to occur inside the hydrophobic ambience of the micelle core [ 9 , 10 ] .\ncleavage of the c = n bonds is a very important transformation in organic synthesis as the c = n functionality is widely used to protect both the carbonyl and amines .\nthere are a number of methods used for the cleavage of c = n bonds which include acidic reagents [ 1113 ] , oxidizing agents , metallic salts [ 15 , 16 ] , ( phseo)2o , nahso3 , and others .\nmost of these methodologies suffer from serious drawbacks like involvement of strong lewis and bronsted acids , use of toxic and costly transition metals ( i.e. , cr , pd , co ) , low temperature , longer reaction time , low yield , and difficulties in isolating the products\n. therefore , development of efficient , mild and environment friendly reagents are always necessary . on the other hand\n, bisindoles are recently emerging as extremely important class of compounds because of their novel antibacterial and anticancer activities [ 1921 ] .\nthat is why a number of methodologies have also been postulated for the synthesis of bisindoles [ 2229 ] . in our previous communications\n, we reported that surfactant- ( sds- ) mediated cleavage of c = n bonds could be achieved with acetic anhydride and surfactant - i2-water can be used for the deprotection of imines to carbonyls .\nwe have also shown that bis- and tris ( indolyl)alkanes can be synthesized in presence of bronsted acid in water . in continuation of our research in hydrated media , herein , we wish to disclose the dual catalytic activity of the system i2-sds - h2o which behaves as a lewis acid for the cleavage of 2,3-diaza-1,3-butadiene , 1-aza-1,3-butadienes , and oximes to produce carbonyls and amines , and the resulting reaction mixture reacts with indoles to produce bis ( indolyl)alkanes in situ at room temperature under neutral conditions .\nfor an initial study , molecular iodine was added to a mixture of 1,4-diphenyl-2,3-diaza-1,3-butadiene ( 1a ) ( 1 mmol ) and indole ( 2a ) ( 2 mmol ) in water .\nit was presumed that the activated imine should produce carbonyl compound in the reaction mixture which might be trapped with indole .\nbut only a trace amount of 3,3-bis(indolyl)phenylmethane ( 3a ) was found to be formed in the reaction .\nwe envisioned that the poor yield of the product may be due to the insolubility of organic substrates in water .\naccordingly , we added a surfactant ( sds ) to the reaction flask . to our delight ,\nthe reaction produced isolable amount of 3a as a brown solid but half of the 1,4-diphenyl-2,3-diaza-1,3-butadiene ( 1a ) left unreacted in the reaction mixture .\nso amount of indole ( 2a ) was doubled ( 4 mmol ) and the same reaction condition successfully produced quantitative amount of 3a .\nthe product was filtered out and the filtrate was treated with freshly distilled benzaldehyde ( 0.05 mmol ) in ethanol which furnished 1a ( m.p .\nthis infers the simultaneous involvement of two c = n bonds of bis - anils , leaving behind hydrazine in the reaction mixture .\nalso , no self - reaction of individual starting materials leading to indole dimer ( 4 ) or pyrrole formation ( 5 ) were observed under the same reaction conditions ( scheme 1 ) .\noptimization of the reaction conditions was undertaken by employing different catalyst loadings under various surfactant conditions .\nit was found that the best result was obtained by the application of 15 mol% of i2 containing sodium dodecyl sulphate ( sds ) and water at room temperature ( entry 1 , table 1 ) . in absence of the catalyst no formation of 3a\nwas observed even after stirring for 24 hours ( entry 5 , table 1 ) . to study the scope and limitations of the reaction ,\ni2-sds - h2o system was applied to the reaction of indole ( 2 ) and 2,3-diaza-1,3-butadiene derivatives ( table 2 , entries a \nthe bisindoles were formed in excellent yields under the reaction condition . it was observed that the reaction was relatively faster when an electron withdrawing substituent , for example , no2 , was present in the phenyl ring of the 2,3-diaza-1,3-butadienes ( table 2 , entry e ) in comparison to the electron donating groups , for example , ome and oh ( table 2 , entries b and f ) .\nidentical results were obtained when 2-methylindole ( 2a ) was used in place of indole ( 2 ) ( table 2 , entries g and h ) .\nall the products were characterized by their ir , h nmr , c nmr , and mass spectral data and also by comparison with the literature report ( scheme 2 ) [ 24 , 25 ] . in order to further explore the efficiency of the i2-sds - h2o system the reaction of the oximes 6 and indoles 2 was studied . when oximes ( 1 mmol ) and indole ( 2 mmol ) were allowed to react under the same reaction condition described earlier , bis - indolylalkanes formed ( table 3 ) . the product was filtered off and the filtrate was treated with benzaldehyde in ethanol .\nthe resulted product was benzaldoxime , which proved the liberation of hydroxylamine during the reaction .\nit was found that no michael addition product was formed and only a trace amount of indole dimer 5 could be identified .\nthe system was also applied to the reaction of 1-aza-1,3-butadienes 7 with indole ( 2 ) which produced bis ( indolyl)alkanes 8 in very good yield eliminating aryl amine in the reaction mixture ( table 4 ) .\nall the products were well characterized by comparison of their spectral and mass data with that of the reported value [ 24 , 25 ] .\nin conclusion , we have shown the dual catalytic activity of i2-sds - h2o system which deprotects the azadienes , oximes , and azabutadienes and produces bis ( alkyl)indoles in situ when indole is present in the reaction medium .\nthe two - step reaction can be carried out without using acid , transition metals , and organic solvents . besides , the reaction condition is mild and can be done in water under neutral condition which contributes to the criteria of green chemistry .\nh nmr spectra were recorded on avance dpx 300 mhz ft - nmr spectrometer .\nchemical shifts are expressed in units relative to tetramethylsilane ( tms ) signal as internal reference .\nir spectra were recorded on ft - ir - system-2000 perkin elmer spectrometer on kbr pellets or in chcl3 .\nthe solvents for chromatography were distilled before use . in a 50 ml round bottom flask\n, 15 mol% of i2 was first dissolved in water ( 10 ml ) .\n2,3-diaza-1,3-butadiene ( 1 mmol ) and indole ( 4 mmol ) were added and stirred in the presence of sodium dodecyl sulphate ( sds ) ( 0.02 g ) for the stipulated time .\nthe product formed was filtered off and washed with water , dried , and recrystallized from ethanol . \nidentical reaction condition was followed when 1-aza-1,3-butadienes and oximes were used as reactants . in this case , 2 mmol of indoles were used to react with 1 mmol of imines .\ncolorless solid ; mp : 150152c ; ftir ( kbr ) : 3418 , 3058 , 1623 , 1611 , 1445 , 1093 cm ; h nmr ( 300 mhz , cdcl3 ) : 5.95 ( s , 1h , ar \nch ) , 6.73(s , 2h ) , 7.06 ( t , 2h , j = 6.8 hz ) , 7.187.27 ( m , 3h ) , 7.317.36 ( m , 2h ) , 7.367.42 ( m , 6h ) , 7.98 ( br , s , 2h , nh ) ; c nmr ( 75 mhz , cdcl3 ) : 40.7 , 111.2 , 119.1 , 119.5 , 120.4 , 122.1 , 123.8 , 126.9 , 126.9 , 128.2 , 129.1 , 136.8 , 144.8 ; hrms calcd for c23h18n2 ( m ) : 322.2851 , found 322.2832 ; anal.calcd . : c , 85.70 ; h , 5.59 ; n , 8.69 ; found c , 85.75 ; h , 5.56 ; n , 8.56 . \npink solid ; mp : 76 - 77c ; ftir ( kbr ) : 3415 , 3060 , 1491 , 1465 , 1095 cm ; h nmr ( 300 mhz , cdcl3 ) : 5.91 ( s , 1h , ar ch ) , 6.76 ( s , 2h ) , 7.08 ( t , 2h , j = 8.3 hz ) , 7.22 ( t , 2h , j = 7.9 hz ) , 7.287.42 ( m , 8h ) , 8.01 ( br , s , 2h , nh ) ; c nmr ( 75 mhz , cdcl3 ) : 39.8 , 111.5 , 122.6 , 123.8 , 127.1,128.4 , 129.8 , 130.1 , 130.9 , 131.0 , 131.6 , 137.2 , 143.5 ; hrms calcd for c23h17n2cl ( m ) : 356.7371 ; found 356.7324 ; anal.calcd .\n: c , 77.52 ; h , 4.77 ; n , 7.86 ; found c , 77.48 ; h , 4.72 ; n , 7.80 . \nbrown solid ; mp : 323325c ; ftir ( kbr ) : 3420 , 1720 , 1455 , 1258 cm ; h nmr ( 300 mhz , cdcl3 ) : 5.98 ( s , 1h , ar - ch ) , 6.85 ( s , 2h ) , 7.107.55 ( m , 11h ) , 8.05 ( br , s , 2h , nh ) ,\nc nmr ( 75 mhz , cdcl3 ) : 34.8 , 107.0 , 110.0 , 111.5 , 117.8 , 119.9 , 120.0 , 122.5 , 124.8 , 127.1 , 136.8 , 142.2 ; hrms calcd for c21h16n2o2 ( m ) : 312.2621 ; found 312.2611 ; anal.calcd .\nc , 80.84 ; h , 5.12 ; n , 8.97 ; found c , 84.05 ; h , 5.15 ; n , 8.94 .\nthe spectral data of the compounds are available in the supplementary material available online at doi : 105402/2012/635835 .", "answer": "a novel catalytic system consisting of i2-sds - h2o has been developed which cleaves 2,3-diaza-1,3-butadiene , 1-aza-1,3-butadienes , oximes and in presence of indoles in the medium uses the corresponding aldehyde products to produce bis(indolyl)alkanes in situ . \n this one pot simple and mild dual catalytic system works in water at room temperature under neutral conditions .", "id": 28} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nAnalysis of membrane binding equilibria of peripheral proteins: allowance for excluded area of bound protein\n\nPaper sections:\n\nThe binding of peripheral proteins to membranes has been the subject of extensive study (for a recent review, see [1]). It is often the case that such proteins do not bind to discrete, specific sites on the membrane, but are electrostatically attracted to the head groups of the phospholipids that make up the membrane, so that the binding process is equivalent to physical adsorption [1]. The difference between binding to discrete sites and physical adsorption appears to have been neglected or glossed over by workers in this field (see for example, [2]). The purpose of the present note is to clarify this distinction and to demonstrate that neglect of the difference can lead to significant quantitative errors in the interpretation of binding data.
We consider the following experiment. A fixed amount of phospholipid membrane, or an equivalent phospholipid surface such as that produced by coating hydrophobic beads with phospholipid [3, 4], is equilibrated with varying amounts of peripheral protein. The amount of peripheral protein bound to the surface of the membrane or phospholipid-coated bead may be measured by a variety of techniques [2]. The quantitative analysis of the dependence of the equilibrium concentration of bound protein upon the total protein concentration proceeds as follows.
Let the total area of membrane per unit volume be given by\n(1)Amem=aLcL,tot where aL denotes the average cross-sectional area of a phospholipid molecule (lipid or L) in the plane of the membrane and cL,tot denotes the molar concentration of L. The fraction of surface area occupied by a concentration cP,bound of membrane-bound protein (P) is then given by\n(2)\u03d5=cP,boundaPcL,totaL=cP,boundnLcL,tot where aP denotes the area of membrane \"covered\" by each molecule of bound protein, and nL the number of lipid molecules \"covered\" by each protein molecule. It may be shown via a general thermodynamic argument [5] that the equilibrium between free and membrane-bound protein is given by\n(3)KcP,free=\u03d5\u03b3P,bound(\u03d5) where K denotes the intrinsic equilibrium association constant for binding of protein to a bare membrane and \u03b3P,bound denotes the thermodynamic activity coefficient of bound protein, a measure of the interaction between bound protein molecules. It may be shown that when the protein binds to discrete equivalent and independent sites, the activity coefficient of bound protein is simply 1/(1 - \u03d5) [5], and that as a result, the membrane binding isotherm may be described by the familiar Langmuir isotherm\n(4)KcP,free=\u03d51\u2212\u03d5 which may be combined with equation (2) to yield\n(5)cP,bound=cL,totnLKcP,free1+KcP,free Equation (5) has been used to model data on the reversible binding of peripheral proteins to membranes. However, to the extent that protein does not bind to discrete and independent binding sites, equation (5) is not a correct description of the binding equilibrium, since it does not allow for the fact that bound protein excludes surface area, and hence potential locations for binding, to other proteins, leading to values of \u03b3P,bound that substantially exceed 1/(1 - \u03d5) with increasing \u03d5.
The dependence of \u03b3P,bound on \u03d5 depends upon many factors, including the size and shape of the cross-section of the bound protein in the plane of the membrane, as well as the presence and magnitude of any interactions between bound protein over and above simple steric repulsion [5]. These details are generally unknown to the experimenter in advance, but in some instances may be deduced by fitting sufficiently comprehensive data with sufficiently sophisticated models [6]. The inadequacy of the na\u00efve Langmuir analysis of membrane binding may be demonstrated by application of the simplest model allowing for area exclusion by bound protein to the analysis of published experimental data.
For the purposes of this demonstration we represent the cross-section of bound protein in the plane of the membrane as a circular disk. It is emphasized that the footprint of an arbitrarily selected protein on a phospholipid surface may not be realistically modeled by a disk. This approximation is employed for didactic purposes only, and resulting parameter values obtained by fitting a model based upon this approximation should not be assumed to be physically realistic. The activity coefficient of the bound \"circular\" protein may thus be estimated using the scaled particle theory for a two-dimensional fluid of hard circular particles [7]\n(6)ln\u03b3P,bound\u2248\u2212ln(1\u2212\u03d5)\u22122+11\u2212\u03d5+1(1\u2212\u03d5)2\n\nAn expression equivalent to equation (6) may be obtained for any footprint describable as a convex polygon [5]. We note that the value of \u03b3P,bound obtained assuming a circular cross-section is the minimum value obtained for any convex hard particle of equal area at constant \u03d5, so that the results shown below represent a lower bound to magnitude of excluded area effects expected for any real steric interaction between bound proteins.
Equation (2), Equation (3), and Equation (6) may be solved numerically to yield the dependence of cP,bound upon cP,tot = cP,bound + cP,free for given values of cL,tot, K and nL. This model was fit via nonlinear least squares to the published data of Cho et al [2] for the binding of phospholipase A2 to phosphatidylcholine-coated beads (cL.tot = 6 \u00b5M) to obtain best-fit values of K = 4.4 (\u22121.0, + 3.5) \u00d7 106 M\u22121 and nL = 11.2 (\u00b12), where the indicated uncertainties correspond to one standard error of estimate. The dependence of cP,bound on cP,tot calculated according to this model with the above-given best-fit values of K and nL is plotted together with the data in Figure 1 (solid line).
For comparison, the Langmuir relation, equation (5), was fit to the same data to obtain best-fit values of K = 8.5 (\u22122, +2.5) \u00d7 106 M and nL = 29.1 (\u00b1 2), in agreement with best-fit values reported by Cho et al [2]. The dependence of cP,bound on cP,tot calculated according to the Langmuir model with the above-given best-fit values of K and nL is plotted together with the data in Figure 1 (dashed line).
Both models fit the data to approximately the same goodness of fit as measured by the sum of squared residuals, so the relative applicability of these two models cannot be distinguished solely on this basis. However, extrapolation of the respective best-fit curves to higher concentration, also illustrated in Figure 1, indicates that additional data obtained at significantly higher protein concentrations would enable such a distinction to be made. Additionally, if we accept the value of nL = 29.1 obtained from the Langmuir analysis, then according to equation (2), the highest amount of protein bound measured in the Cho experiment (0.175 uM) would correspond to a fractional area occupancy of around 85%. Chatelier and Minton [5] demonstrated unequivocally that in the absence of attractive interactions between adsorbed proteins leading to cluster formation, it is impossible to attain such a large fractional area occupancy at equilibrium with any experimentally attainable total protein concentration. So the Langmuir model, which does not take into account either repulsive or attractive interactions between bound ligand, cannot provide a physically reasonable interpretation of the Cho data that are treated in this MS.
The present example demonstrates that failure to take into account steric repulsion between peripheral proteins bound to a membrane may lead to significant overestimates of binding affinity and the number of lipid molecules \"covered\" by a protein molecule. Note that this number is not equivalent to the number of lipid molecules comprising a \"binding site\", since there are no specific binding sites for protein on a featureless phospholipid membrane.
The Langmuir analysis is valid only at very low levels of area occupancy by bound protein (\u03d5\u2212 1). This condition obtains in measurements such as those reported by Kim et al [8]. However, it follows from equation (5) that the apparent binding constant reported by these authors is not the actual binding constant K, but rather the quantity K/nL. In order to estimate the quantitities K and nL independently, it is necessary to measure ligand binding at sufficiently high values of \u03d5 to enable application of the full analysis described above, and even in this case it is necessary to make assumptions regarding the cross-sectional area of adsorbing protein and tendency of adsorbed protein to self-associate, both of which affect the dependence of \u03b3 on \u03d5[6]. The values of K and nL derived from modeling the experimental data will thus be subject to more or less uncertainty depending upon the reliability of these assumptions.
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", "answer": "When peripheral proteins bind to phospholipid membranes lacking discrete binding sites, steric repulsion between bound protein molecules may result in a reduction of the surface area available to additional bound protein by an amount significantly greater than the actual area occupied by bound protein. An approximate treatment of this effect demonstrates that neglect of area exclusion by bound protein may lead to significant errors in the evaluation of equilibrium association constants and the fractional coverage of membrane surface area.", "id": 29} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprostate cancer is a common health problem that in the majority of cases starts to develop at the age of 50 years , reaching its peak at 6070 years of age .\na variation in its incidence and prevalence exists between western , asian and arabic populations .\nthe highest incidence is in the usa and canada followed by european countries , then the asian population and the lowest incidence is in arabic population [ 1 , 2 ] .\nthe incidence of prostate cancer was reported to be about 100127/100.000 men in the usa , while only 3.1 , 3.3 and 6.5/100.000 men in saudi arabia , oman and kuwait .\nthe marked difference in the incidence and prevalence of prostate cancer between western and arabic countries is very interesting and can be attributed to different explanations .\nall arabic countries are actually islamic countries where muslims constitute the majority of the population .\nthey adopt male circumcision in the first few years of life as an obligatory event in relation to the religion of islam .\ninterestingly , many recent studies confirmed the association between circumcision and the lower incidence of penile viral infections .\nuganda trial reported that applying male circumcision results in a reduced incidence of hsv2 infection by 25% , hpv infection by 35% and hiv infection by 5060% [ 7 , 8 ] .\nmorris recently reported that male circumcision is a surgical vaccine that guards against genital and urinary bacterial and viral infection and protects against penile and prostate cancer . in a study of 20,243 men in finland , infection with hpv18\nwas associated with a 2.6fold increase in risk of prostate cancer ( p < 0.005 ) . for hpv16 ,\nsome studies reported that uncircumcised men have more than twice the incidence of prostate cancer compared with circumcised men [ 1214 ] which explains why prostate cancer is relatively rare amongst jews .\nof men operated on for prostatic obstruction , 1.8% of obstructions were cancerous in jews ( circumcised ) , compared with 19% of non jews ( uncircumcised ) .\na study in the uk in 1996 found an odds ratio for the reduction in risk of prostate cancer in circumcised men to be 0.62 .\ntable 1 illustrates some recent publications studying the association between male circumcision , stds and prostate cancer . \n \npublications studying the association of circumcision with sexually transmitted diseases and prostate cancer the age standardized incidence rate of prostate cancer is lower in asian countries than in the united states and european countries .\nhowever , the incidence rate in asians living in the united states is substantially higher than that in those living in their homelands .\nmigration studies have shown an increase in prostate cancer incidence in asian men after emigration to the united states .\nthis observation suggests that environmental factors and changes in lifestyles , particularly in dietary practices , can affect the aetiology of prostate cancer\n. a higher intake of vegetables in the arabic population may be also a factor that contributes to the lower incidence of prostate cancer .\na recent study from egypt confirmed higher vegetable intake to be of significant value in reduction of the risk of prostate cancer . a recent systematic\nreview confirmed that a diet low in fat and meat and rich in vegetables and fruits is recommended to lower the risk for prostate cancer .\nstudied the difference in serum testosterone between arab and german groups of patients with diseases other than prostate cancer and was able to demonstrate a significantly lower level of testosterone in the arab population in the middle age group ( < 30 years ) , pointing out that the relatively lower level of serum testosterone in that age group may be protective in the long run . in another study ,\nthe same group published the difference in levels of serum testosterone between arabs and american caucasians and reported lower levels o in arabic men in all age groups , with a higher significance in the middle age groups ( < 30 years ) .\nschistosomiasis is a parasitic disease that is endemic in tropical countries with more than half of the cases located in africa and middle east .\nanimal studies on the effect of schistosomal infection on the testes confirmed that schistosomal infection results in a significant decrease in the level of serum testosterone [ 2427 ] .\nanother endemic problem that emerged in egypt , secondary to schistosomiasis , is caused by the treatment itself . in the mid20 century , the egyptian ministry of health began to conduct mass treatment in rural areas and for every suspected infection using tartar emetic intravenous injection . at that time , the dangers of exposure to human blood were n't considered and disposable needles and syringes were not available [ 28 , 29 ] .\nfrank et al . reported a direct relationship between parenteral treatment of schistosomiasis and the country wide prevalence of antibodies to hepatitis c infection .\nmany studies [ 30 , 31 ] confirmed the association between hepatitis c infection and chronic liver disease with the occurrence of hypogonadotropic hypogonadism manifested by low serum level of gonadotropic hormones and serum testosterone .\ntable 2 illustrates findings in publications correlating serum testosterone in arabic and western populations . \n \npublications correlating serum testosterone in arabic and western populations serum psa is a widely used parameter for the early detection and monitoring of prostate cancer . in western countries men with total psa < 2.5\nng / ml have a low probability of having prostate cancer , while those with psa > 10 ng / ml have > 50% chance of having prostate cancer [ 3234 ] .\na recent paper from kuwait , demonstrated that for cases with psa > 10 ng / ml , prostate cancer was still of a low probability , with the majority of cases with elevated psa only suffering from prostatitis or bph .\nthey could detected a psa value of > 50 ng / ml to carry 100% specificity for prostate cancer in the arabic population .\na recent paper from saudi arabia studying the incidence of prostatic adenocarcinoma in patients admitted to king abdul \naziz university hospital showed that prostate cancer was detected in 28.5% of patients with psa > 4 ng / ml , which is considered lower than the expected incidence for their patients median age group of 68 years .\ntable 3 demonstrates the difference in incidence between the findings in the saudi arabia study with a canadian and a multi institutional studies . \n \nincidence of prostate cancer in different recent studies another arabic study compared age adjusted serum level of psa of the arabic population with that of usa caucasians and the japanese population .\nthey showed that usa whites tend to have the highest total psa , followed by japanese population and finally the lowest psa level , adjusted to age , was present in arabic population .\npsa density ( psad ) is another important parameter that was introduced by benston and colleagues as a useful tool to increase specificity of the detection of prostate cancer .\ndifferent cut off values of psad ranging from 0.1 to 0.15 was proposed by urologists aiming to increase the specificity of prostate cancer detection in the grey zone area of total psa level , and thus avoid unnecessary prostatic biopsies [ 4144 ] .\ncontrary to studies on the western population , a recent arabic study , trying to include psad as a mean to avoid unnecessary prostatic biopsy , concluded that in patients with total psa < 10 ng / ml , values of psad < 0.32 strongly suggest benign disease .\nthe aim of our work was to report the pattern of prostate cancer presentation in alexandria university that as a tertiary referral center , provides care for uro oncology cases .\ndata collection for all patients diagnosed with prostate cancer at alexandria universityin egypt through the year 2012 was done .\nall possible information including patients age , clinical presentation , dre findings and serum total psa and prostate volume were evaluated .\nanalytical analysis was done using two tailed fisher exact test and two tailed unpaired t test .\nwe found 950 patients diagnosed with prostate cancer in our database through the year 2012 .\nmean serum total psa , prostate volume and psad were 149 ng / ml , 63 grams and 3.1 ng / ml / gm respectively .\nthe remaining group was presenting with luts , including 23 patients who presented initially with back pain .\npatients characteristics only 7 patients were found to fulfill the criteria of low risk prostate cancer namely , psa < 10 , t1c and gleason grade < 7 .\nsymptomatic patients were significantly associated with finding suspicious nodules during dre ( p 0.002 ) and higher psa density ( p 0.01 ) .\npsa density of 0.15 did not yield any significant difference between both symptomatic and asymptomatic groups .\nthe median psa density for the whole group was 0.425 . when we used that value as the cutoff value , symptomatic patients had significantly higher psa density values .\ntable 5 shows the analytical analysis for the studied groups . \n analytical analysis for asymptomatic and symptomatic cases\nonly 54 patients ( 25% ) were diagnosed through surveillance programs for prostate cancer ( annual total psa and dre ) without having any symptoms .\nthirty three patients had suspicious findings on dre and 42 patients had serum total psa > 10 ng / ml . the striking features in those groups were the high psa density and that most of the cases ( 46 patients ) had a gleason grade > 6 .\nirritative urinary symptoms were the main presenting complaints in our patients and the same findings of markedly higher psa density and higher gleason grade were noted . using\nthe suggested western psa density value of 0.15 did not give any significant difference between surveillance and symptomatic groups , as the majority of cases had a psa density > 0.15 .\nwe decided to use psa density value of 0.425 as the cut off value , being as it was the median value from the all 216 cases .\nthe surveillance group had 65% of cases with a value < 0.425 , while the symptomatic group had 46% of patients with values < 0.425 ( p 0.01 ) .\nthat in the arabic population , a high psa density value up to 0.32 may present benign disease .\nour study also confirms the pivotal role of dre in the diagnosis of patients with prostate cancer as 77% of our cases had a suspicious finding during examination .\nit was clear that patients diagnosed with prostate cancer in egypt , regardless of their mode of presentation and whether screened or not , tend to have a high serum total psa , psa density , abnormal findings on dre and higher gleason grade , reflecting the aggressive nature of prostate cancer in the egyptian population ( using the western definitions ) .\na recent paper from nigeria showed that abnormal dre can predict higher gleason grades .\nour study shows that prostate cancer may not be a single disease throughout the world and racial , religious and life style conditions may be contributing factors that affect the nature and presentation of the disease . applying western definitions\nwould mean that nearly all of our cases already had a metastatic and advanced disease , while really only 11% of them had metastatic deposits .\nour reports confirm that egyptian men with prostate cancer had higher psa , psa density and higher gleason grade at initial diagnosis and tailored risk stratification may be needed to allow proper management for our cases .\negyptian men with prostate cancer have a markedly high psa density and gleason grade at diagnosis .", "answer": "introductionprostate cancer is a common health problem that in the majority of cases starts to develop at the age of 50 years , reaching its peak at 6070 years of age . \n a variation in its incidence and prevalence exists between western , asian and arabic populations.the aim of our work was to report the pattern of prostate cancer presentation in alexandria university that as a tertiary referral center provides care for uro \n oncology cases.material and methodsdata collection for all patients diagnosed with prostate cancer at alexandria university in egypt through the year 2012 was done.resultsthe mean age of the patients was 67 . \n mean serum total psa , prostate volume and psad were 149 ng / ml , 63 grams and 3.1 ng / ml / gm respectively . \n 25% of patients were asymptomatic diagnosed accidentally during screening for prostate cancer . \n the remaining group was presenting with luts , including 23 patients who presented initially with back pain.conclusionsegyptian men with prostate cancer have a markedly high psa density and gleason grade at diagnosis .", "id": 30} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsimultaneous palmar dislocation of the scaphoid and lunate is rare [ 17 ] and has been classified into two types depending on whether or not the scapholunate ligament is intact .\nten patients with dislocation of the scaphoid and lunate as a unit have been described to date , as well as six patients with divergent dislocation [ 16 ] .\nthe patient described here is therefore the seventh with palmar - divergent dislocation of the scaphoid and lunate . in this patient\n, the scapholunate and lunotriquetral ligaments were sutured through the dorsal approach , the anterior capsule was sutured through the palmar approach , and the scapholunate and lunotriquetral joints were fixed with kirschner wires . to our knowledge , this is the first report in which interosseous ligaments were sutured by open surgery for divergent dislocation of the scaphoid and lunate .\na 46-year - old man who fell from a height of 1.5 m onto his left hand was brought to the emergency center of our hospital and underwent a medical examination .\nradiography of the wrist revealed palmar - divergent dislocation of the scaphoid and lunate ( fig . 1 ) but with no neurovascular disturbance in the hand .\nseven days after the injury , open surgery was performed through the palmar and dorsal approaches .\nthe dorsal approach showed ruptures of the scapholunate and lunotriquetral ligaments , which were sutured with anchors .\nthe palmar approach showed an oblique tear of the anterior capsule , which was sutured with absorbable threads .\nfinally , the scapholunate and lunotriquetral joints were fixed with two kirschner wires , inserted from the scaphoid to the lunate and from the triquetrum to the lunate , respectively , and the wires were buried under the skin ( fig . 2 ) .\na short arm plaster splint was applied postoperatively ; 2 weeks later , it was changed to a removable splint and rehabilitation was started . as kirschner wires remained in the carpal bones , range of motion ( rom ) exercises of the wrist were restricted to avoid wire failure . at 7 weeks , the kirschner wires and splint were removed , and the patient was started on intensive rehabilitation for an additional 3 months . at the 1-year follow - up , the patient had returned to normal life and work and had no pain in his wrist , although wrist motion was still restricted .\nmeasurements of wrist and forearm rom showed that right / left extension was 60/50 , flexion was 70/40 , supination was 90/80 , and pronation was 90/90. a hand dynamometer showed that grip strength in his left hand was 16 kg compared with 27 kg on the contralateral ( dominant ) side .\nalthough we observed no evidence of dorsal or volar intercalated segment instability pattern deformity , radiography showed a break in arc ii of gilula s line between the lunate and triquetrum , as well as flexion deformity of the scaphoid ( fig . \nmagnetic resonance imaging showed no evidence of avascular necrosis of the scaphoid and lunate ( fig . \n1radiographs at initial diagnosis showing palmar - divergent dislocation of the scaphoid and lunatefig . \nthe scapholunate angle was 54 and the radiolunate angle 6. gilula s line was well - regulatedfig . \nthe scapholunate angle was 67 and the radiolunate angle 0. dorsal intercalated segment instability ( disi ) deformity was not observed , although there was flexion of the scaphoid and a break in arc ii of gilula s line at neutral and ulnar deviationfig . \n4magnetic resonance imaging at the 1-year follow - up showing no evidence of avascular necrosis of the scaphoid and lunate radiographs at initial diagnosis showing palmar - divergent dislocation of the scaphoid and lunate postoperative radiographs showing good alignment of the carpal bones .\nthe scapholunate angle was 54 and the radiolunate angle 6. gilula s line was well - regulated radiographs at the 1-year follow - up .\nthe scapholunate angle was 67 and the radiolunate angle 0. dorsal intercalated segment instability ( disi ) deformity was not observed , although there was flexion of the scaphoid and a break in arc ii of gilula s line at neutral and ulnar deviation magnetic resonance imaging at the 1-year follow - up showing no evidence of avascular necrosis of the scaphoid and lunate the patient provided written informed consent prior to inclusion in this study , which was authorized by the local ethics committee and performed in accordance with the ethical standards of the 1964 declaration of helsinki as revised in 2000 .\nas palmar - divergent dislocation of the scaphoid and lunate is rare , its optimal treatment remains unclear . in previous reports ,\ntwo patients were treated by open reduction and cast immobilization [ 1 , 2 ] , two by open reduction and percutaneous pinning of the carpal bones and cast immobilization [ 3 , 4 ] , one by open reduction and suture of the anterior capsule and cast immobilization , and one by proximal row carpectomy ( prc ) ( table 1 ) .\ncarpal instability is severe in divergent dislocation due to ruptures of both the scapholunate and lunotriquetral ligaments .\ntherefore , it is difficult to stabilize the carpal bones and still retain sufficient wrist motion.table 1review of previous patients with divergent dislocation of the scaphoid and lunateauthorfollow - up ( months)surgical procedureapproachimmobilization ( duration)k - wire removalrange of motioncomplicationscampbell 12only open reductionpalmarcastnr \next 1/2flex 1/3 of healthy sidenonegordon 12only open reductionpalmarcast4 weeks ext 15flex 25disikupfer 42open reduction k - wire pinning ( s - l)palmar & dorsalcast4 months4 monthsext 25flex 0crps disi an ( scaphoid , lunate)baulot 42open reduction anterior capsule suturepalmarcast6 weeksalmost fulldisikang 18open reduction k - wire pinning ( s - l / s - c)palmarcast6 weeks6 weeksalmost fullnonedomeshek 1proximal row carpectomypalmar & dorsalsplint1 month nrnran avascular necrosis , nr not recorded , k - wire kirschner wire , s scaphoid , l lunate , t triquetrum , c capitate , disi dorsal intercalated segment instability , crps complex regional pain syndrome , ext extension , flex flexion review of previous patients with divergent dislocation of the scaphoid and lunate an avascular necrosis , nr not recorded , k - wire kirschner wire , s scaphoid , l lunate , t triquetrum , c capitate , disi dorsal intercalated segment instability , crps complex regional pain syndrome , ext extension , flex flexion among the methods recommended to repair , the anterior and posterior ligaments on both sides of the lunate are combined palmar and dorsal approaches , and open reduction and percutaneous pinning of the scapholunate and scaphocapitate joints without suture of the interosseous ligaments .\nalthough we found that suturing of the dorsal scapholunate and lunotriquetral ligaments provided a satisfactory outcome in our patient , wrist stiffness , carpal malalignment due to a break in arc ii of gilula s line between the lunate and triquetrum , and flexion of the scaphoid still remained .\nfirst , we should have sutured the palmar , not the dorsal , lunotriquetral ligament because the palmar ligament is stronger .\nmoreover , in addition to fixing the scapholunate and lunotriquetral joints with kirschner wires , we should have fixed the scaphocapitate joint to maximize anatomical carpal alignment .\nthus , for reliable carpal stability , we recommend ligament repair and temporary joint fixation of the carpal bones .\nsubsequent wrist stiffness may be prevented by early removal of kirschner wires after surgery and starting wrist exercises .\nindeed , it may be possible to remove kirschner wires earlier than 6 weeks when interosseous ligaments are sutured . the injury to our patient\nprc on a patient with a scapholunate dislocation and complete scaphoid extrusion resulted in a good clinical outcome , suggesting that prc may eliminate avascular necrosis and avoid additional surgery in patients with this type of injury .\nhowever , although prc has shown satisfactory clinical outcomes , postoperative rom and grip strength averaged 5070% and 6090% , respectively , compared with the healthy side , outcomes similar to those observed in our patient .\ntherefore , except when unavoidable , we recommend surgical repair , especially for active young people and manual workers , with prc considered a salvage procedure .", "answer": "we describe a patient with palmar - divergent dislocation of the scaphoid and lunate . \n after successful closed reduction , the scapholunate and lunotriquetral ligaments were sutured through the dorsal approach , and the anterior capsule was sutured through the palmar approach . \n the scapholunate and lunotriquetral joints were fixed with kirschner wires for 7 weeks . at the 1-year follow - up , \n magnetic resonance imaging showed no evidence of avascular necrosis of the scaphoid or lunate , and radiographs showed no evidence of the dorsal and volar intercalated segment instability patterns associated with carpal instability . however , flexion of the scaphoid and a break in gilula s line remained . to our knowledge , this is the first report showing treatment of palmar - divergent dislocation of the scaphoid and lunate by suturing the carpal interosseous ligaments .", "id": 31} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin 2007 , a 14-year - old male killer whale at a marine park in san antonio , texas , usa , died suddenly without notable premonitory signs . on gross examination , mild multifocal meningeal hyperemia and petechial parenchymal hemorrhage\nfocally extensive tan discoloration and fibrosis were present in the right accessory lung lobe with associated hemorrhage and congestion .\ntissues fixed in 10% buffered formalin were processed routinely and stained with hematoxylin and eosin for histologic examination .\ninflammatory lesions of the central nervous system were focused in gray matter of the medulla oblongata , pons , mesencephalan , and cerebellum .\nblood vessels demonstrated mild to moderate acute necrosis and lymphocytic and contained plasmacytic and neutrophilic infiltrates within vascular walls .\nencephalitis was characterized by perivascular lymphocytes and fewer plasma cells expanding the virchow - robbins spaces .\npredominant lesions in the lungs were areas of chronic and active abscessation amid a focally extensive area of mixed inflammation and fibrosis .\nthey were characterized by central ulcerations with necrosis and a mixed inflammatory infiltrate surrounded by variable fibrosis and a rim of epithelial hyperplasia .\nchanges in spleen , lymph node , and kidney included acute edema , congestion , and vascular dilation .\nconventional diagnostic assays were performed for aerobic , anaerobic , and fungal microbes in liver , lung , kidney , cerebrospinal fluid , and brain .\nthe final diagnosis was fulminant peracute bacteremia and septicemia secondary to a primary viral infection associated with nonsuppurative encephalitis .\npublished etiologic considerations for cetacean nonsuppurative encephalitis include morbillivirus and protozoal infections ( 2 ) .\na dna microarray with highly conserved sequences from > 1,000 viruses was selected to screen for known and novel viruses ( 3 ) .\ntotal rna was extracted from brain tissue and hybridized to a microarray as described ( 4 ) .\nanalysis of the resulting hybridization pattern demonstrated a strong hybridization signal to many oligonucleotide probes on the microarray from the family flaviviridae , in particular to wnv .\nconsensus reverse transcription pcr primers ( 5 ) targeting wnv were used to confirm the microarray results .\nhq610502 ) yielded a sequence with 99% nt identity and 100% aa acid identity to wnv strain ok03 ( genbank accession no .\neu155484.1 ) , a strain originally identified in oklahoma , usa . to further support a wnv diagnosis , we performed immunohistochemical staining on brain tissue .\nrockville , md , usa ) with peroxidase - tagged goat antirabbit immunoglobulin g ( dakocytomation , carpinteria , ca , usa ) bridge and 3-amino-9-ethylcarbazole ( dakocytomation ) as the chromogen .\nthis staining demonstrated abundant wnv antigen within the cytoplasm of a small number of neurons and glial cells and in fewer macrophages in the brain tissue ( figure ) .\nbrain specimen from killer whale ( orcinus orca ) with west nile virus infection that died at a marine park , san antonio , texas , usa , 2007 . neurons and glial cells demonstrate abundant intracytoplasmic west nile viras antigen .\nwe evaluated wnv exposure within the same cohort , as well as a geographically distant cohort of whales by using serologic testing .\nall testing was performed at the same laboratory by using a standard plaque - reduction neutralization test . in this assay ,\na 90% neutralization cutoff was used ( 6 ) . a 90% plaque - reduction titer\nserum from the affected whale and 5 cohort killer whales from the same marine park in san antonio as well as 5 whales housed at another facility in orlando , florida , usa , were evaluated . in each facility , the animals have regular contact with each other .\nthe facilities are geographically separated so the animals do not have exposure to those in the other park .\nall 6 animals from texas had 90% plaque - reduction titers > 10 , ranging from 40 to 80 .\nthese findings broaden the known host tropism of wnv to include cetaceans in addition to previously known pinnipeds .\nalthough we can not definitively attribute the cause of death of this whale to wnv , the observed lesions are consistent with those caused by wnv in other animals .\nthe serologic results demonstrate that subclinical infections can occur and that exposure can be variable .\nboth bexar county , texas , and orange county , florida , have had wnv in wildlife since 2002 .\nmosquito management practices are similar in both facilities and have been expanded since this diagnosis .\ndifferences in wnv prevalence or mosquito numbers may have played a role in the different serologic results .\nhealth evaluations of free - ranging and captive cetaceans should include wnv serology to assess exposure rates .\nthis report focuses on killer whales , but the loafing behavior ( stationary positioning at the water s surface ) is commonly seen in many coastal dolphins , thereby increasing the likelihood of mosquito bites and exposure to wnv .\nserologic screening of bottlenose dolphins ( tursiops truncatus ) from the indian river lagoon demonstrated wnv titers ( 7 ) .\nas with many species of birds and mammals , wnv infection carries a risk for zoonotic transmission .\nuntil the implications of this infection in marine mammals are better understood , biologists and veterinarians working with cetaceans should consider this possibility .\npotential viral shedding can occur through the oropharygeal cavity and feces as well as through blood and organs during necropsies .\nfinally , our study demonstrates the broad applicability of using panviral microarray - based diagnostics .\neven though pcr diagnostics are well developed for wnv , the agent was not initially considered as a potential pathogen in this species .\npanviral microarray can be used not only to identify novel viruses but also to detect unsuspected agents .", "answer": "in 2007 , nonsuppurative encephalitis was identified in a killer whale at a texas , usa , marine park . \n panviral dna microarray of brain tissue suggested west nile virus ( wnv ) ; wnv was confirmed by reverse transcription pcr and sequencing . \n immunohistochemistry demonstrated wnv antigen within neurons . \n wnv should be considered in cases of encephalitis in cetaceans .", "id": 32} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 3.09 kg , 33-day - old boy with pierre robin syndrome was admitted to our hospital for a glossopexy .\nthe patient was born at 39 weeks by c - section and was diagnosed with the syndrome during pregnancy . after birth , the patient showed a micrognathia , retrognathia , and a large tongue .\nthe patient also showed moderate chest retraction with coarse breathing sounds presenting difficulty in maintaining patent upper airway .\nhe was kept in a prone / lateral position under 5 l / min of o2 hood at nicu until the operation . in the operating room\nintraoperative monitoring devices such as an ecg , an automatic blood pressure cuff , and a pulse oximeter were applied to the patient .\nthe initial oxygen saturation was 98% in room air and other vital signs ( bp : 96/27 mmhg , pr : 161/min , rr : 42/min ) were in normal ranges .\na mask was applied before induction and the manual ventilation was well maintained with patient 's spontaneous ventilation .\npremedication with 0.004 mg / kg of glycopyrrolate was given intravenously and anesthesia was induced with gradual increment of sevoflurane concentrations from 2% to 4% with oxygen by mask while also maintaining spontaneous respiration .\nbrief direct laryngoscopic examination with a curved mcintosh blade ( # 1 ) was performed and only the hypopharynx was seen .\nclassical reusable laryngeal mask airway ( lma ) # 1 , in which two vertically placed bars were removed , was inserted and effective ventilation was assured by chest expansion , auscultation , and etco2 monitoring . while pausing the ventilation , ultrathin fiberoptic bronchoscope ( fob ) ( olympus enf type xp , 1.8 mm od , length : 530 mm , tokyo , japan ) was passed through the lumen of the lma and the vocal cords were well visualized .\nunder the visualization of the vocal cords by the fob , we passed the cook airway exchange catheter ( caec ) ( 1.6 mm i d , 2.7 mm od ) ( cook medical incorporated , bloomington , in , usa ) through the lma into the vocal cords .\nhowever , passing the caec into the vocal cords under the guidance of the fob repeatedly failed because the caec frequently flexed backwards toward the esophagus . at that time , we recognized that the length of an uncuffed i d 3.0 mm endotracheal tube ( length : 16 cm ) was longer than that of lma#1 ( length : 11 cm ) .\ntherefore , through the lma , the tracheal tube was mounted on the fob and introduced into the trachea .\nsuccessful ventilation was verified by manual ventilation . to prepare for any accidental removal of the tracheal tube while removing the lma , we inserted the caec into the lumen of the tracheal tube . after placing the caec in the midtrachea ,\nlma was carefully removed while tightly holding both the caec and tracheal tube simultaneously . despite this , the endotracheal tube was displaced out of the vocal cords while removing the lma . by holding the caec firmly inside the trachea , the displaced endotracheal tube\nafter intubation , endotracheal tube position was verified again by auscultation of equal bilateral breathing sounds and etco2 . during the procedure\n, anesthesia was maintained with intermittent sevoflurane administration in oxygen ( o2 : 1 l / min , air : 1 l / min ) through the lma to prevent awakening and desaturation of the patient .\nthe maximum time allowed for the procedure was until the spo2 decreased lower than 95% .\natracurium 1.5 mg was given intravenously for muscle relaxation and mechanical ventilation was maintained during the operation .\nthe extubation was carried out when the patient was in a completely alert state and the spontaneous ventilation was well maintained without any chest retraction following the extubation .\nthe patient was then transferred to nicu in the supine position under 5 l / min of o2 mask .\npatients with pierre robin syndrome may create difficulties during intubation and airway control is a major concern for anesthesiologists .\nventilation using a face - mask in the presence of a markedly recessed mandible may be difficult and patient 's supine position frequently leads to a total obstruction of the airway .\nvisualization of the larynx is almost impossible once the patient is anesthetized . in a recent survey conducted amongst pediatric anesthetists in canada\n, 73% stated that they first attempted a direct laryngoscopy and , in the case of a failure , 51% would choose laryngeal mask airway - guided fiberoptic intubation .\nwhen fob is chosen to be used for intubation , most anesthesiologists generally tend to use lma as a conduit for the bronchoscope , indicating that this technique is now firmly established in an approach to the difficult pediatric airway .\nalthough this approach seems to be very successful , one problem is that the endotracheal tube can be easily withdrawn from the trachea during the removal of the lma . in order to prevent this , selim et al\ntherefore , it was possible to keep the intubated tube patent inside the trachea while lma was being removed , but instability of an elongated tube has still been a problem .\nin addition to this , some authors used a long guide wire inserted into the suction port of the fiberscope , which was then placed inside the trachea under direct vision . having the guidewire left in the trachea ,\nthe fiberscope and lma were withdrawn , and the tracheal tube was railroaded over the guidewire .\na disadvantage of this method was that the guidewire can be easily bent and flipped out of the trachea .\nosses et al . introduced a method of using an adult intubating stylet attached to the end of the tracheal tube so that lma would be removed while pushing the stylet inward . as an alternative approach , we used the caec under the guidance of the fiberscope to ease the insertion of the endotracheal tube into the trachea . however , when this catheter was passed down through the lma , it frequently emerged from the posterior aspect of the mask aperture of the lma and resulted in an esophageal intubation even though vocal cords were well - visualized with the ultrathin fob . despite many trials using a caec , it was very difficult to approach the vocal cords with the tip of the catheter .\nbrimacombe and berry have reported that the success rate of blind placement of the caec via the lma in adults was only 30% despite good lma positioning .\ntherefore , this indicates that , even when the lma is perfectly positioned , blind tracheal intubation can not always be performed successfully . in children , perfect positioning of the lma\nwas observed in 44% , 29% , and 49% of all cases , which also indicates that there may have been some impediment to blind passage of the endotracheal tube , a bougie or introducer when this technique is attempted . to correctly place the caec into the trachea ,\nafter the guidewire passed through the suction channel of the fob , a stiffening device such as the caec or ureteral dilator railroaded over the guide wire through the lma might be helpful in placing the caec or dilator correctly in the trachea .\nin addition to this , we suggest another method for successful placement of the caec . as shown in fig .\n1 , a fishing line is passed through the lumen of a caec and form a guide - loop like the one of arndt endobronchial blocker ( cook medical incorporated , bloominton , in , usa ) at the distal end of the caec and a tight knot is made at the proximal end of the catheter , making sure that it does not come loose .\nthen , the fob and lma were removed while keeping the catheter in midtrachea and the endotracheal tube is mounted on the caec , followed by railroading over the caec . in a pediatric patient , weighing 7.5 kg , thomas and parry also used a caec through which a fob was inserted and the tip of the fob was extended from the distal aperture of the caec . following introduction of caec with the enclosed fiberscope into the trachea , the fob was removed leaving the caec within the trachea .\nalthough this is an interesting approach , considering that they used an olympus lf - p fiberscope ( proximal od 2.2 mm and distal od 1.8 mm ) and a caec ( 2.3 mm i d for use with tracheal tubes of i d 4 mm or larger ) , it can not be used in a smaller pediatric patient because the olympus enf type xp or lf - p fiberscope can not pass through the lumen of the caec ( 1.6 mm i d for use with tracheal tubes of 3 mm or larger ) which we used .\nanother problem with this approach is that the caec has to be cut to an adequate length to ensure that the fob tip extends from the distal aperture of the caec . in our case ,\nan uncuffed 3.0 mm i d endotracheal tube ( length : 16 cm ) was longer than that of lma#1 ( length : 11 cm ) .\nhowever , in pediatric difficult airway cases in which the endotracheal tube length is similar to or shorter than the lma , the proximal end of the tracheal tube tends to disappear into the lma once the tracheal tube has passed through the vocal cords . in this situation\n, it might be helpful to insert a caec first through the lma using the suggested methods by walker , thomas and parry 's methods , or our method in order to facilitate easy insertion of the caec into the trachea . in summary\nfirst , it can provide a more stable passage for the endotracheal tube since the diameter of the caec which we used ( 1.6 mm i d ) is larger than the guide wire previously used to pass through the suction port .\nsecond , it is much safer to attempt repeated intubation in the case of accidental tube displacement out of the trachea during removal of the lma .", "answer": "the case of a 33-day - old boy with pierre robin syndrome using a cook airway exchange catheter in laryngeal mask airway - guided fiberoptic intubation is presented . \n after induction with sevoflurane , classical reusable laryngeal mask airway ( lma ) # 1 was inserted and ultrathin fiberoptic bronchoscope ( fob ) was passed through . a cook airway exchange catheter ( 1.6 mm i d , 2.7 mm od ) was passed through the lma under the guidance of the fob but failed to enter the trachea despite many trials . \n then , an endotracheal tube ( 3.0 mm i d ) was mounted on the fob and railroaded over the fob . after successful intubation \n , the cook airway exchange catheter was placed in the midtrachea through the lumen of the endotracheal tube . \n even though the tracheal tube was accidentally displaced out of the trachea during lma removal , the endotracheal tube could be easily railroaded over the airway exchange catheter .", "id": 33} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunilateral neglect ( un ) refers to the neuropsychological condition in which patients \n experience reduced orientation and concentration and response to stimuli on the \n contralesional side owing to behavioral problems that occur after brain injury , although \n these patients having sensorimotor abilities1 .\nun is caused by various forms of brain damage and has an especially \n high incidence in patients with stroke in the right inferior parietal lobe2 .\nit is \n negatively associated with the rehabilitation period because patients with un show \n relatively poor functional recovery compared with those without un3 .\nin addition , these patients experience difficulties in \n activities of daily living ( adl ) , including maintaining personal hygiene , eating , and \n dressing , and also are at increased risk of falling because of gait disturbance4 . therefore , having an appropriate treatment \n and strategy are important while treating this condition because it is essential to reduce \n un to achieve effective rehabilitation in these patients .\nwe proposed a new treatment method for un by modifying current treatment methods and \n combining them with mental practice and electromyogram - triggered electrical stimulation \n ( mp - emg es ) .\nmp - emg es is a new , state - of - the - art rehabilitation treatment technology based \n on neurologic theories .\nmp - emg es involves only repetitive mental practice ( for example , \n imagination of intense movement of the upper limbs on the neglected side ) , not voluntary \n muscular contraction . when the generated electric potential reaches a preset threshold , an \n electric stimulus is generated , resulting in actual muscular contraction and cortical \n activation5 .\nin other words , mp - emg es \n can produce a synergistic effect by combining two treatments ( mental practice plus \n electrical stimulation ) with proven efficacy in the alleviation of neglect .\nthe purpose of \n this study was to identify the effects of this novel training method \nmp combined with emg \n es over a 6-week period of daily training in patients showing right brain damage with \n un .\nthe participants for this study were recruited from the rehabilitation center of a local \n university hospital .\nthe inclusion criteria for participation were : ( 1 ) onset duration of \n > 6 months , ( 2 ) right hemisphere stroke with un , ( 3 ) mini - mental status \n examination score > 24 , ( 4 ) ability to imagine ( average score on the \n vividness of movement imagery questionnaire < 3 ) , and ( 5 ) active wrist muscle strength \n > 2 on the medical research council ( mrc ) scale .\nexclusion criteria were : ( 1 ) an implanted \n cardiac pacemaker , ( 2 ) skin lesion on the affected side or hypersensitivity at the electrode \n site , ( 3 ) a history of seizure or epilepsy , and ( 4 ) unstable medical conditions . in total , \n thirty - three stroke patients with neglect were eligible for this study .\nall participants \n provided written informed consent , and this study was approved by the inje university \n institution review board .\nthis study was designed as a single - blind randomized control study and was scheduled to \n last for a total 6 weeks .\neligible participants were randomly allocated to the two groups by \n block randomization using opaque envelopes containing a code specifying the group .\nthe \n experimental group ( n=16 ) received mp - emg es in addition to conventional rehabilitation \n therapy ( crt : physical therapy and occupational therapy ) , whereas the control group ( n=17 ) \n received cyclic es in addition to the same crt .\nmentamove ( mentamove deutschland gmbh , \n munich , germany ) was used to apply mp - emg es in the experimental group .\nsurface electrodes \n were attached to the wrist extensor muscle and a reference electrode was attached at the \n lateral side of the forearm .\nthe site of electrode placement was marked using a permanent \n marker throughout the intervention . during motor imagery training ,\nwhen the potentials reached \n a preset threshold , the induced electrical stimulation would contract the targeted \n muscle .\nthe mentamove process consisted of three stages : ( 1 ) motor imagery ( approximately 12 s ) , \n ( 2 ) electrical stimulation ( approximately 6 s ) , and ( 3 ) relaxation ( approximately 12 s ) .\nthe \n motor imagery used in this study was a vigorous waving of the affected whole arm .\nthis \n imagery was selected because the emg was not able to detect electrical stimulation induced \n by motor imagery of simple extension of the wrist or elbow .\nthe emg pick - up threshold was \n set afresh for each subject in every session .\nif the subject repeatedly reached the \n threshold during the mp - emges , the threshold was automatically increased slightly .\nimagine that your left \n arm moves rapidly and intensely when you see motor imagery in the tool window .\nif your \n performance is successful , you will experience an electrical stimulation in your forearm .\ncyclic es ( mendel gmbh , germany ) without the emg function was used to apply electrical \n stimulation in the control group .\nelectrodes also were attached to the wrist extensor \n muscle . in either instrument , biphasic pulses with a frequency of 35 hz and pulse width of \n\n200 s were applied for 12 s. stimulation intensity led to a clear extension of the wrist \n ( average 2030 ma ) . over a period of 6 weeks , both groups were treated 30 times in two \n 30-min sessions . the line bisection test ( lbt ) , star cancellation test ( sct ) , and catherine bergego scale \n ( cbs ) were used to quantify the severity of un .\ntwenty lines were drawn on an \n a4 sheet parallel to the long axis , and 18 of these lines were organized into 3 set of 6 : 1 \n set lay primarily on the left , 1 at the center , and 1 on the right side of the sheet .\nthe \n evaluator initially demonstrated the procedure by marking the 2,150-mm lines at the top and \n bottom of the sheet .\npatients were asked to mark the center points of each of the 18 lines \n in order .\ndistances from the left of each line to patient s marks and to true line centers \n were measured .\ndeviations were measured using the formula : percent deviation ( % ) = [ ( marked \n left side distance - true half length)/true half length ] 100 . in sct ,\nthe left and right halves \n of the sheet each contained 27 stars , and patients were asked to mark all of the stars .\nthe \n scores range from 0 to 27 , with lower scores indicating more severe un .\nassessment using cbs \n involved evaluating the performance of patients by directly observing them perform \n activities ( e.g. , dressing , grooming ) in real - life situations , and consisted of 10 items . \n\neach item was scored on a four - point scale as follows : 0 : no neglect 110 : mild neglect , \n 1120 : moderate neglect , and 2130 : severe neglect7 .\nparticipant characteristics were analyzed using a statistical software program ( spss \n statistics 20 ) and descriptive statistics were presented as mean sd . the shapiro - wilk test \n was used to check normality of the outcome variables . to evaluate the intervention effects , \n measures before and after the intervention in each group\nan independent t - test was used to compare changes in outcome measures between the \n two groups .\nall demographic and clinical characteristics of the participants were comparable and are \n summarized in table 1table 1.baseline characteristics of the subjects included in the studyexperimental group ( n=16)control group ( n=17)gendermale10 8 female69age ( years)67.510.362.210.2time post stroke ( months)3.31.33.51.6stroke typehemorrhage45infarction1212 .\nthe experimental group showed a significant improvement in the lbt ( p<0.01 ) , cbs , and sct \n ( p<0.05 ) scores after the intervention compared with the values obtained before the \n intervention ( table \n 2table 2.clinical parameters before and after the treatment ( n=33)experimental group control groupbeforeafterbeforeaftercbs12.14.210.14.612.63.811.24.1lbt30.58.924.110.332.69.127.710.6sct10.65.213.05.5 9.25.211.04.6the values are mean standard deviation .\ncbs : catherine bergego scale , lbt : line \n bisection test , sct : star cancellation test .\n* p<0.05 by paired t test between the \n initial and final scores in the group .\non the other hand , no significant difference was observed in the control \n group , except in the lbt score ( p<0.05 ) .\nno significant differences were observed in the \n lbt , cbs , and sct scores between the two groups after treatment .\ncbs : catherine bergego scale , lbt : line \n bisection test , sct : star cancellation test .\n* p<0.05 by paired t test between the \n initial and final scores in the group .\nmp - emg es is a recently developed method that produces tiny electrical signals in the brain \n through mental practice , rather than through actual physical movements , and this method is \n used to induce muscle contraction in the upper extremity ( u / e ) on the neglected side . in \n other words ,\nthe aim of mp - emg es is to form sensorimotor circuits for movement through a \n repeated cycle of brain signal transmission muscle movement , which can be used to \n produce functional changes in the central nervous system and the body .\nthe continual \n activation of these circuits helps reorganize the damaged areas of the cerebral cortex8 .\nit is thought that mp - emg es works by \n inducing neural and peripheral changes through activation of the cerebral cortex via mental \n practice and afferent stimulation of the neglected u / e via electrical stimulation .\nhong et al.5 reported mp - emg es is more \n effective than cyclic es for improving motor function on the affected side and improves \n cerebral glucose metabolism in supplementary motor , precentral and postcentral gyri on the \n contralesional side .\nhowever , there is little evidence about the effects of this treatment \n in cases of un . in this study\n, we investigated the effects of mp - emg es on neglect in \n comparison with those of cyclic es .\ncbs , lbt and sct scores significantly improved after \n treatment in the experimental group .\nthe control group received various crt interventions \n that were the same as the experimental group .\nthis control treatment was important because \n cyclic es has been proven to alleviate neglect to some extent by applying afferent \n stimulation to the neglected side .\ntherefore , while the control group only showed a \n significant improvement in lbt , they also showed a slight improvement in scores for cbs and \n sct , and as a result , no significant differences were demonstrated between the two groups in \n any assessments .\nsome studies \n reported that mental practice is effective for rehabilitation in patients with \n contralesional neglect , but it is difficult to verify whether patients imagine the specific \n movement well9 .\nmp - emg es seems to remedy \n the deficiencies of mental practice alone . in this study , patients were instructed to imagine a large and powerful movement of the \n neglected u / e during the mental practice stage of mp - emg es treatment . when imagining the \n movement of the neglected u / e , the muscles in the u / e show dynamic regulation and \n changes5 .\nin this regard , when a \n participant imagined a complex and powerful movement instead of a simple movement , the \n motor - evoked potential and the excitation in the corticospinal tract increased10 .\nthis study showed that mp - emg es is an effective method for reducing unilateral neglect in \n stroke patients .\nhowever , several factors need to be considered when applying this method . \n because mp - emg es requires the patient to be capable of imaging movement of the body on the \n neglect side", "answer": "[ purpose ] the aim of this study was to investigate the effect of mental practice combined \n with electromyogram - triggered electrical stimulation on neglect and activities of daily \n living in stroke patients with unilateral neglect . [ subjects and methods ] thirty - three \n stroke patients with unilateral neglect were recruited from a local university hospital , \n and were divided into two groups . \n the experimental group received an intervention \n consisting of mental practice combined with electromyogram - triggered electrical \n stimulation on the neglected side , while the control group received cyclic electrical \n stimulation at the same site . \n in addition , both groups received an identical intervention \n of conventional occupational and physical therapy . \n [ results ] after the intervention , the \n experimental group showed a statistically significant improvement in the line bisection \n test result , star cancellation test result , and catherine bergego scale scores . \n the \n control group showed a significant improvement only in the line bisection test result . \n \n [ conclusion ] these data suggest that mental practice combined with \n electromyogram - triggered electrical stimulation is an effective , novel treatment for \n reducing unilateral neglect in stroke patients .", "id": 34} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvoluntary exercise has been found to mitigate harmful consequences of stress on the brain and to prevent the expression of depression and anxiety - like behavior .increased activity of brain - derived neurotrophic factor ( bdnf ) signaling is suggested to be an important factor mediating the benefits seen after running.in agreement , stress and depression have been found to decrease bdnf expression [ 2 , 3 ] .\ncorticotrophin - releasing factor ( crf ) is the major hypothalamic mediator of stress and is also involved in the etiology of depression and anxiety - like behavior [ 4 , 5 ] and has been found to be downregulated in the mouse hypothalamus following exercise [ 6 , 7 ] .\ncrf acts through the seven transmembrane , g - protein - coupled receptor crf receptor 1 ( crfr1 ) , initiating the release of cortisol in humans and corticosterone in rodents from the adrenal gland .\nthe cloning of a second crf receptor ( crfr2 ) [ 911 ] , existing as two primary splice variants ( crfr2 and crfr2 ) , was followed by the discovery of three additional crf family members , the urocortin 1 ( ucn1 ) , urocortin 2 ( ucn 2 ) [ 13 , 14 ] , and urocortin 3 ( ucn 3 ) . in general , there is a limited overlap in the distribution of crf and the crf receptor subtypes and of the urocortins , suggesting separate but complementary functional roles .\nthe physiological roles of crfr2 in the brain are still somewhat elusive , but most reports in the literature suggest involvement in dampening the body 's response to stress . \nthus , mice deficient in crfr2 ( crfr2 / ) exposed to restraint stress show rapid and elevated acth levels compared to control animals , and behavioral studies show an increase in anxiety - like behaviors , possibly due to increased crf mrna levels in the central nucleus of the amygdala .\nhowever , studies using agonists and antagonists against crfr2 indicate that the attenuation of depression and anxiety - like behavior in relation to activated crfr2 is complex .\nthus , the effects has been found to be diverse , site specific , and depending on the stress level and experimental model as well as being different between genders .\nthe lateral septum ( ls ) , a brain area important in the shaping of coping responses to stress and found to modulate the activity in the amygdala , exhibits the highest density of crf2 in the brain . here\n, we have studied crfr2 and bdnf in the female mouse ls using quantitative real - time reverse transcriptase polymerase chain reaction ( qrt - pcr ) in an exercise paradigm .\nbrain punch biopsies from young female mice exposed to voluntary exercise and nonexercised age- and sex - matched controls were analyzed for expression levels of transcript for bdnf and crfr2 in ls .\nin addition , crf mrna was studied in the central nucleus of amygdala ( cea ) , as this is a key site for the integration of central stress circuits . \nfinally , we monitored the exercise - induced effects on morning corticosterone and leptin levels in plasma as well as the weight of abdominal fat mass .\nthe experiment was performed in 20 nave , 5-week - old c57/bl6 female mice ( scanbur , sollentuna , sweden ) . all experimental procedures in animals\nwere approved by the animal care and use committee at linkping university and in accordance with the european communities council directive guidelines .\nthe mice were housed individually under standard conditions with free access to water and food under a 12-h light and 12-h dark cycle ( lights on at 07:00 am ) .\nthe experimental groups ( n = 10 ) had access to a wheel ( : 13 cm ) for three weeks , and the housing of the control group ( n = 10 ) remained unchanged .\nvaginal smears were used to assess the stage in the estrous cycle and all females were in the estrous phase at the end point of the experiment .\nthe amount of running was on average 8,000 revolutions per day with peaks during the proestrus phase . for analysis of gene expression by qrt - pcr\n, the mice were euthanized after three weeks at 9.00 am by means of decapitation .\nblood was immediately withdrawn from the right ventricle by heart puncture , collected in edta containers ( sarstedt ab , landskrona , sweden ) and centrifuged at 7,000 g ( 4c ; 10 min ) .\nthe brains were dissected out , sliced , and put on ice , and punch biopsies were collected under a microscope using an air - powered punching machine following a microdissection protocol .\ntotal rna was extracted using rneasy lipid tissue mini kit ( qiagen , sollentuna , sweden)including dnase treatment and rna was reversely transcribed to cdna ( applied biosystems , foster city , calif , usa ) .\nquality control of rna extraction was performed on each brain area using the agilent rna 6000 nano assay protocol ( http://www.agilent.com/chem/labonachip/ ) according to their protocol .\nreal - time rt - pcr was performed on an applied biosystems 7900 fast real - time pcr system using taqman fast universal pcr master mix according to the manufacturer 's instructions ( applied biosystems , stockholm , sweden ) .\nthe taqman gene expression assays used were : bdnf = mm 01334042-m1 ; crfr2 = mm 00438303-m1 ; b - actin = mm 00607939-s1 and gapdh = mm 99999915-s1 as endogenous controls .\neach gene was normalized with the corresponding average of b - actin and gapdh expression in the same animal and expressed as the fold difference in relation to the control group . \nmorning corticosterone was measured by means of an enzyme immunoassay ( oc - teia ) , according to the manufacturer 's instruction ( ids nordic , herlev , denmark ) .\nassay sensitivity was 0.55 ng / ml . leptin concentration was measured by means of bead - based xmap luminex technology ( austin , tex , usa ) , using a commercially available kit ( electrabox , tyres , sweden ) according to the manufactures protocol .\ndata were acquired as mean fluorescence intensity , collected by the star station software program ( applied cytometry systems , dinnington , sheffield , uk ) .\ndata were analyzed with anova followed by student 's t - test to ascertain which group differed significantly from controls .\nhere , we report a 3-fold increase in bdnf gene - expression levels in the ls following three weeks of voluntary running ( p < 0.05 ) ( figure 1 ) . to our knowledge , this is the first demonstration that bdnf mrna levels in the female ls are markedly increased following long - term exercise .\nbdnf has a multitude of actions on neurons , and dysfunction of this neurotrophin may modulate mood .\nexercise has been found to induce bdnf - mediated increase of neurogenesis , and increased bdnf gene - expression and protein following acute or long - term exercise results in mood benefits and enhanced memory [ 3 , 21 ] .\nhowever , studies of exercise - induced effects on bdnf in other brain areas and circuits other than hippocampus are limited .\nin addition , we studied the effect after voluntary exercise on crfr2 , since the ls harbors substantial levels of crfr2 and since this receptor has been reported to mediate coping responses during the recovery phase after stress [ 4 , 22 ] . in the present study ,\ncrfr2 gene - expression was , however , not altered after three weeks exercise nor was cea expression of crf mrna although we found a trend towards an increase in crfr2 ( figure 1 ) .\nplasma concentrations of morning corticosterone were decreased by approximately 18% compared to the control group ( 15,3 1,6 ng / ml ; 12,6 2,4 ng / ml , p < 0.01 ) ( figure 2 ) , which may suggests that it is possible that a part of the hpa - axis is inhibited by voluntary long - term exercise . however\nwe used female mice , since anxiety and depression are twice as common in females , and there is accumulating evidence that the crf system also outside hypothalamus is differently regulated when comparing female and male rodents .\nthe amount of voluntary running in females is closely correlated to the levels of sex hormones .\nwe observed what others also have found that the average frequency of running where higher during the proestrus phase when there is a peak in estrogen levels .\nwe chose to collect the brains the day at estrus when estrogen levels are low , since it is known that bdnf is regulated by this sex hormone itself at least in the hippocampus .\nthus , bdnf - synthesizing neurons express estrogen receptors , and the bdnf gene contains an estrogen responsive element , suggesting possible interactions between estrogen and bdnf regulation [ 25 , 26 ] .\nour working hypothesis was that since acute exercise initiates the activation of the hpa - axis , crfr2 might be activated to counteract the crf / crfr1 system in the amygdala through the ls .\nthus , the activation of the crf system in the amygdala is tightly correlated to stress and anxiety - like behavior . however , neither crfr2 nor crf mrna were changed after three weeks running . taken together , if crfr2 and ls are involved in the strategies of stress coping , it seems that long - term voluntary exercise is a situation when ls crfr2 and cea crf are not activated . \n< 0.05 ) ( figure 2 ) , in parallel with a 30% reduction in fat mass ( p < 0.001 ) .\nfood intake and water consumption was not measured in the present study , but previous studies of mice using the same experimental model showed no difference in food intake in exercised animals versus controls , and no difference between groups in total body weight , similar to what we observed .\nleptin is a 16 kda protein hormone and a product of the obese gene that has been found to be correlated with the lipid content of the cells and plays an important role in regulating food intake and energy expenditure .\nit has been shown in both humans and mice that weight loss is associated with a decrease in plasma leptin .\nas already mentioned , we did not observe any changes in total body weight but a decrease in perigonadal fat pads .\na decrease in abdominal fat in combination with no weight loss is probably due to an increase in muscle weight after long - term exercise .\nit is possible that the decrease of plasma leptin in the present study is correlated to the decrease in perigonadal fat .\nhowever , further studies are needed , since the mechanisms responsible for regulating leptin expression and protein are complex and not fully understood at least not in females . in summary , these data show for the first time that long - term voluntary exercise increases bdnf gene expression but not crfr2 in the ls or crf in the cea in young healthy female mice .\nalthough our data show that the bdnf gene is activated by exercise in the ls , the limitation is that we did not measure bdnf protein levels .\nhowever , it is possible that exercise may promote ls neuronal survival through increased bdnf , but this needs to be further elucidated .\nin addition , to what extent this is related to an effect on depressive and anxiety - like behavior remains to be analyzed and would be an intriguing future perspective .", "answer": "voluntary physical activities are known to modulate anxiety and depressive / like behaviors in both animals and humans . \n brain derived neurotrophic factor ( bdnf ) , has been reported to be elevated following exercise . \n bdnf , as well as type 2 corticotrophin releasing factor receptor ( crfr ) 2 , has been shown to mediate anxiety - like behavior . in the present study we examined the effects of long - term voluntary exercise on the transcripts for bdnf and crfr2 in the lateral septum ( ls ) and for crf in the central amygdala ( cea ) in female mice . \n thus , increased activity of crf in the cea is associated with anxiety - like behavior . \n quantitative rt - pcr was employed to measure levels of mrna in punch biopsies from ls and cea . \n in addition , measurements of the concentration of corticosterone and leptin in plasma were employed . in the ls \n , we found a three - fold increase of bdnf mrna ( p < 0.05 ) but no significant change in crfr2 mrna . no changes in crf in the amygdala were observed but we found a decrease in the levels of plasma corticosterone . \n plasma leptin and the weight of perigonadal fat pads were decreased following exercise . in conclusion , these data show that bdnf gene expression in the ls is influenced by long - term exercise in females but not crfr2 .", "id": 35} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is surprising that a medline search reveals less than 10 articles on topics concerning adult thalassemia .\nthere is a severe resource data crunch at a time when information needs to be readily available to the physicians , the emphasis being on evidence - based medicine .\n this study aims to evaluate the clinical profile of thalassemia major patients surviving into adulthood so as to orient the physicians and the general practitioners to adult thalassemia patients .\nthe study included all adult patients of thalassemia ( > 18 years old ) who are attending the adult thalassemia care unit ( department of medicine ) for their management .\nthe department of pediatrics at our institute , which happens to be a tertiary institute , runs a thalassemia day care unit , wherein about 250 patients regularly receive transfusion and all patients who attain 18 years of age are referred to adult thalassemia care unit ( department of medicine ) for management , from where these data are being reported .\nall patients were evaluated clinically and investigated for complete blood counts , serum urea , creatinine , bilirubin ( total and direct ) , alanine and aspartate transaminases , alkaline phosphatase , total protein and albumin , fasting and postprandial plasma glucose , serum ferritin , and thyroid hormone levels .\nall the patients were receiving packed cell transfusions for at least 15 years with the aim to keep the hemoglobin levels at about 10 g / dl .\nunpaired student 's t - test was used to ascertain difference in clinical features between male and female thalassemia patients .\na total of 19 thalassemia patients were above the age of 18 years and were availing regular transfusion services at fortnightly intervals .\nas is evident from the table , the height in both the male and female subjects was quite lower than the usual height in indian adults .\nonly three males and one female had a height exceeding 150 cm , the maximum height achieved by a male subject being 168 cm and for the female 151 cm .\nthe average height in male thalassemics was significantly higher than that in females ( unpaired t - test , p=0.023 ) . despite the fact , the height was below average , the bmi was < 18.5 in eight thalassemia patients ( 42.1% ) and only one ( 5.3% ) had a bmi>25 i.e. 25.44 .\nclinical features of thalassemia patients nearly half of the patients ( 47.4% ) had undergone splenectomy by the time they reached their adulthood . interestingly ,\n72% males had undergone splenectomy as compared to 12.5% female thalassemics ( unpaired t - test , p=0.005 ) .\naverage hemoglobin was similar in both male and female subjects but six ( 31.6% ) had their hemoglobin levels < 8 g / dl .\naverage leukocyte counts were higher in males ( unpaired student 's t - test , p=0.0058 ) .\nmoreover , two ( 18.2% ) males and four ( 50% ) females had total leukocyte counts < 4000/mm .\nsurprisingly , no patient had achieved the recommended serum ferritin levels of < 1000 ng / ml .\nin fact , serum urea , creatinine , total proteins , and albumin levels were within the normal range for all patients .\nfour patients ( 21.1% ) had serum bilirubin levels > 1.5 mg/ dl with a predominant indirect hyperbilirubinemia .\none patient was positive for both hepatitis b and c virus infections and three others were only positive for hcv and one other harbored hiv infection . in total five ( 26.3% ) patients were harboring at least one of the three infections .\nfour ( 21.1% ) of the patients were receiving a combination of two iron - chelating drugs - deferiprone and desferrioxamine , while the remaining were receiving only deferiprone .\naverage dose of deferiprone being administered to each patient was 958 mg / kg body weight daily in divided doses .\nthalassemia is an autosomal recessive disorder and thalassemia major manifests as severe anemia in infancy or childhood and used to be incompatible with life in the absence of regular red cell transfusions .\nhowever , hematopoietic stem cell transplantation ( hsct ) has offered a prospect of cure with a normal life expectancy and quality of life , relief from life - long blood transfusions and its attendant complications .\nshort of hsct , thalassemia major patients need a two - pronged therapy in the form of transfusion \nit is only thalassemia minor / trait which may be diagnosed in adulthood and does not carry a great clinical significance being asymptomatic in majority of individuals .\nhowever , with increasing number of thalassemia major patients surviving through their adolescence into adulthood , adult physicians should brace themselves to face the challenge of dealing with thalassemia in their adult patients .\n what adult thalassemics will be like has been presented in this article . in spite of improvements in transfusion practices and availability of effective iron chelators , the life of thalassemia patients\nthe complications relate to inadequate transfusions , inadequate chelation , transfusion - transmitted viral infections , allosensitization , iron overload and its consequences of endocrine , cardiac , hepatic disturbance ; iron - chelator - related drug toxicities ; osteoporosis and psychosocial problems.[24 ] lack of proper and trained medical expertise , periodic requirement of safe and adequate packed red cell concentrates high cost of in - line leukocyte - depleting filters and iron - chelator drugs ; and poor compliance with blood transfusions , periodic monitoring , and regular chelation pose other major hurdles for the thalassemics .\ninadequate transfusions are a rule rather than the exception in india resulting in hypersplenism and greater rates of splenectomy .\na total of 31.6% patients had hemoglobin levels < 8 g / dl and 47.4% adult thalassemics had undergone splenectomy in the present study .\nhowever , this finding could not be corroborated because of lack of similar published studies .\nthe high total leukocyte counts observed in males can be explained as a consequence to splenectomy .\nthe low average height , weight , and the bmi in both males and females are signs of growth failure commonly seen in inadequately chelated beta - thalassemics .\nnormal serum protein and albumin levels rule out protein energy malnutrition as a cause of growth failure .\nserum ferritin levels were high in all patients , a testimony to inadequate chelation in this group .\nthis is despite the fact that all thalassemics were receiving iron chelation , either deferiprone alone or in combination with desferrioxamine .\neven the average dose of deferiprone while being used as monotherapy was 95 mg / kg / day ( range being 85114 mg / kg / day ) against the recommended dose of 75 mg / kg / day in divided doses . in fact\n, one study citing that deferiprone was not found sufficiently effective at the recommended dose of 75 mg / kg / day , tried a high dose of 100 mg / kg / day for 2 years and found it to be safe and effective .\nhowever , in the present study in adult thalassemics , deferiprone is not effectively chelating even at this high dose , so a higher dose may need to be tried or patients shifted to alternative iron chelators like deferasirox .\nrepeated blood transfusions are associated with the serious risk of transmission of chronic viral infections , which were observed in 26.3% of the cases in the present series .\nantibodies to hepatitis c virus were observed in 21% cases and the same figure has been reported from indian thalassemics .\naverage serum transaminase values are higher than normal in the present study and can be attributable to chronic viral hepatitis .\nthe absence of diabetes , hypothyroidism , cardiac arrhythmias in the present cohort can possibly be explained by the young age ( early adulthood ) , since these are a consequence of iron overload and the prevalence therefore increases with the number of blood transfusions and so with the age .\nindeed , one indian study did not report diabetes or impaired glucose tolerance in chronically transfused patients of thalassemia major between 8 and 15 years of age .\nhowever , cardiac involvement can not be entirely ruled out since it requires echocardiography and mri to see for the functional and structural effects of iron overload , respectively .\nosteoporosis and osteopenia are extremely frequent in thalassemia affecting from 52% to 96% of patients and the prevalence rises with age .\nechocardiography , mri , and dexa scan were not performed for the thalassemia patients in the preceding 1 year and could not be done as part of the study in view of cost constraints .\nthis study presents a profile of the adult thalassemia subjects and provides insight into the problems and complications faced by them despite several medical advances .\nthe onus of dealing with these lies squarely with the adult physician and it is imperative for one and all to be aware of these .", "answer": "background : effective transfusion and chelation have prolonged the quality and longevity of life in thalassemics , who now survive into adulthood . hence , adult physicians need to be aware of their clinical and laboratory profile and the problems faced by them.aim:the present study was aimed to evaluate the clinical profile of adult thalassemics.materials and methods : adult ( > 18 years ) thalassemia major patients ( n=19 ) were evaluated clinically and fasting pretransfusion blood samples were analyzed for complete blood counts , kidney and liver function tests , plasma glucose , serum ferritin , and thyroid hormone levels.results:average age was 21.652.47 years ( range 1928 years ) , 42.1% had body mass index ( bmi ) < 18.5 . \n splenectomy had been performed in 47.4% before reaching adulthood , males significantly outnumbered females ( 72% vs. 12.5% ) . hemoglobin levels < 8 g / dl were observed in 31.6% and none had serum ferritin levels in the recommended range suggesting inadequacy of both transfusion and chelation . \n indirect hyperbilirubinemia was observed in 21.1% patients although kidney functions , serum protein , and albumin were normal in all patients . \n electrocardiographic abnormalities , diabetes mellitus or hypothyroidism were absent . \n five patients ( 26.3% ) had contracted transfusion - transmitted viral infections \n 21.1% and 5.3% respectively had antibodies to hepatitis c virus and hiv , while 5.3% were positive for australia antigen . \n all patients were receiving chelation therapy \n deferiprone alone ( 78.9% ) or along with desferrioxamine ( 21.1% ) . \n average dose of deferiprone being used was 958 mg / kg.conclusion : adult thalassemia major patients present with a distinct clinical profile having low bmi , generalized hyperpigmentation , most are splenectomized , have low hemoglobin , inadequate chelation and harbor transfusion - transmitted infections . \n adult physician needs to be aware of this profile .", "id": 36} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is well established that the transition of vascular smooth muscle cells ( vsmcs ) from a differentiated phenotype to a dedifferentiated state plays a critical role in the pathogenesis of atherosclerosis .\nthe phenotypic modulation in vsmcs is accompanied by accelerated migration , proliferation and production of extracellular matrix components .\neventually , these cellular events result in the formation of atherosclerotic lesions . however , the molecular mechanisms involved in phenotypic control are still unclear\n. micrornas ( mirnas ) are a class of endogenous , small , non - coding rnas that pair with sites can in 3 ' untranslated regions in mrnas of protein - coding genes to downregulate their expression .\nmore importantly , one mirna is able to regulate the expression of multiple genes because it can bind to its mrna targets as either an imperfect or a perfect complement .\nthus , a mirna can be functionally as important as a transcription factor . as a group , mirnas\nit is therefore not surprising that mirnas are involved in the regulation of all major cellular functions .\nrecently , the role of mirnas in cardiac cell differentiation has been described . in this study , kwon et al . demonstrated that mir-1 plays important roles in modulating cardiogenesis and in maintenance of muscle - gene expression by targeting transcripts encoding the notch ligand delta .\nthe biological roles of mir-145 in diverse cancer cells have been recently identified ( reviewed in ) . in a recent article reported by xu et al .\n, mir-145 was found to be a critical switch for embryonic stem cell differentiation by repressing some core pluripotency factors . whether mirnas participate in the phenotypic control of vsmcs was unknown until recently . in this respect ,\nthree independent groups have reported exciting new discoveries regarding the critical role of the vsmc - enriched mirna , mir-145 , in vsmc phenotypic modulation [ 8 - 10 ] .\nthey identified that mir-145 plays a role not only in the differentiation of multipotent neural crest stem cells into vsmcs , but also in the differentiation of adult vsmcs .\nother mirnas that may participate in the phenotypic modula tion of vsmcs are mir-143 and mir-221 [ 9 - 12 ] .\nthis minireview summarizes the current research progress regarding the roles of mir-145 in the vsmc phenotype and the potential therapeutic opportunities of mirnas in atherosclerotic vascular disease .\nji et al . demonstrated that mir-145 is the most abundant mirna in arteries . its expression is significantly downregulated in rat balloon - injured arteries with neointimal lesion growth .\na recent nature article by cordes et al . showed that mir-145 expression was also decreased in mouse carotid arteries after ligation injury .\nmore interestingly , transcripts of mir-145 were down regulated to nearly undetectable levels in atherosclerotic lesions containing neointimal hyperplasia .\nour own unpublished data also revealed that mir-145 is largely downregulated in atherosclerotic mouse and human arteries , although the downregulation is less pronounced compared with that from cordes ' study .\nif the selected atherosclerotic tissue had fewer vsmcs , the expression level of mir-145 could be lower .\nrecently , cheng et al . found that mir-145 is the most abundant mirna in differentiated vsmcs .\nalso , its expression is quickly downregulated in subcultured dedifferentiated vsmcs and in dedifferentiated vsmcs induced by stimulation with platelet - derived growth factor ( pdgf ) .\nour unpublished data also indicate that mir-145 expression in vsmcs isolated from balloon - injured rat carotid arteries and atherosclerotic apoe - knockout mouse aortas is significantly decreased compared with that in vsmcs isolated from normal control arteries .\n. found that , during the development of arteries , the expression of mir-145 is associated with the state of vsmc differentiation .\nmir-145 expression is notably absent in the aorta and pulmonary arteries during later cardiogenesis , during which vsmcs and arteries are developing .\nin contrast , high transcript levels of mir-145 in vsmcs of the arteries are demonstrated postnatally , after vsmcs and arteries have completed their development .\ncordes et al . demonstrated that mir-145 was necessary and sufficient to induce differentiation of multipotent neural crest stem cells into vsmcs .\nin addition , cheng et al . identified for the first time that mir-145 is a critical modulator for the vsmc phenotype both in vitro and in vivo .\nvsmc differentiation marker genes such as sm -actin , calponin , and sm - mhc were downregulated by mir-145 downregulation , and upregulated by mir-145 upregulation . the regulatory effect of mir-145 on the vsmc phenotype\nwas further verified by cordes and colleagues . in contrast , another co - expressed mirna , mir-143 , had no significant effect on marker genes for vsmc differentiation , although it had a strong effect on vsmc proliferation .\n. demonstrated that the expres sion of the mir-143/145 cluster is confined to vsmcs during development .\nthey found that mir-143 and mir-145 are required for vsmc acquisition of the contractile phenotype because the vsmcs from mir-143/145-deficient mice are locked in the synthetic state .\nthe regulatory effects of mirnas on the vsmc phenotype are not limited to mir-143 and mir-145 .\ntwo recent studies revealed that mir-221 is also related to the vsmc phenotype that affects vsmc proliferation and migration .\nit is well known that phenotypic modulation of vsmcs is an initial cellular event in the development of atherosclerotic vascular disease . to determine the therapeutic potential of mir-145 in vascular disease ,\n. demonstrated that restoration of mir-145 in rat balloon - injured carotid arteries via adenovirus - mediated gene transfer significantly inhibited neointimal lesion growth .\nin contrast , knockout of mir-143 and mir-145 resulted in the formation of neointima in mouse arteries .\nthe roles of mir-145 in the vsmc phenotype and atherosclerotic vascular disease are summarized in figure 1 .\nexpression modulation of mir-145 in the vascular walls and the potential roles of mir-145 in vascular smooth muscle cell phenotype and atherosclerosis .\nits expression is significantly downregulated in developing arteries and in adult arteries containing intimal hyperplasia .\nthe downregulated mir-145 in adult arteries will increase vsmc dedifferentiation and result in the development of atherosclerotic lesions .\nmirna - based therapy may have some advantages compared with that for other molecular targets because one endogenous mirna can target its multiple target genes .\nalthough the recent studies have demonstrated that targeting mirnas , and mir-145 in particular , may represent a new therapy for atherosclerosis , there is still a long road before mirna - based technology can be translated to clinical therapy .\nfirst , the critical mirnas responsible for the development of atherosclerosis must be further identified , especially in human atherosclerotic arteries .\nsecond , the detailed cellular and molecular mechanisms of these critical mirnas in the prevention and treatment of atherosclerosis should be studied .\nthird , in addition to the biological effects of these mirnas on vsmcs , their effects on other atherosclerosis - related cellular events should be identified .\nfourth , although methods are available to downregulate a mirna in vivo , technology for upregulating a mirna in the vascular walls in vivo requires development . finally , the potential side - effects of mirna - based therapy should be studied before application in the clinic .\nmirna : microrna ; mir-145 : microrna-145 ; pdgf : platelet - derived growth factor ; vsmc : vascular smooth muscle cell .\nthis work was supported by a national institutes of health grant hl080133 and a grant from the american heart association 09grnt2250567 .", "answer": "micrornas ( mirnas ) represent a class of small , non - coding rnas that negatively regulate gene expression via degradation or translational inhibition of their target mrnas . \n recent studies have identified that mir-145 is the most abundant mirna in normal arteries and vascular smooth muscle cells ( vsmcs ) , and its expression is significantly downregulated in dediffer - entiated vsmcs and atherosclerotic arteries . \n mir-145 plays a critical role in modulating vsmc phenotype . \n because phenotypic modulation of vsmcs is an initial cellular event in the development of atherosclerosis , mirnas , and mir-145 in particular , may represent new therapeutic targets for atherosclerosis .", "id": 37} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmigraine is a chronic disease of the brain that enhances morbidity with complains like photophobia , headache attacks , phonophobia , and nausea . in the second edition of the headache classification by the international headache society ,\nmigraine is among the primary headaches and migraine without aura , migraine with aura , migraine cursors in childhood , retinal migraine , and migraine complications are grouped as potential migraines . according to the results of the turkish headache database ,\nthe number of female patients is 4 times that of male patients . there were 84% of the adults who were migraine without aura patients , and 14% who were migraine with aura patients .\nalthough most of these patients have been found to have comorbidity with other diseases , eye diseases were excluded from those studies ; however , photophobia is reported to be the most frequent accompanying symptoms .\nthe vision system is reported to play a role , especially in migraine with aura headaches .\none of 5 patients with a headache is directed to the department of eye diseases , mostly because almost all migraine with aura patients have visual auras .\nthe relationship between migraine and refractive errors has been studied for more than 100 years ; however , conflicting results have emerged from those studies [ 79 ] . in this study , we compared the auto - refractometric values of migraine patients with and without visual aura , with those patients without migraine complaints .\nwe prospectively compared the patients who consulted the neurology policlinic between june 2013 and march 2014 with a headache complaint and diagnosed with migraine in accordance with the ichd-2 criterion with the individuals of the same gender and age group with no headache complaint .\nthis study adhered to the tenets of the declaration of helsinki and was carried out with the approval of the institution .\nthe patients were given full detailed eye examinations and findings were noted . out of these patients , those over age 18 years who had 20/20 uncorrected vision and who did not have ocular pathology in their examination were included in the study .\nthe patients were divided into 3 groups : group 1 : 86 eyes of 43 migraine patients without aura ; group 2 : 38 eyes of 19 migraine patients with aura ; and group 3 : 60 eyes of 30 patients without headache . the same ophthalmologist examined the patients in the period with no headache .\nthe corrected and uncorrected vision of right eye and left and bilateral eye of all the patients were individually measured .\nthose patients whose uncorrected vision did not have 20/20 value for both eyes separately and bilaterally were excluded from the study .\nthe 3-dimensional vision and eye movements of the patients were evaluated by the worth 4-point test and those patients who failed this test were excluded from the study .\nbiomicroscopic and fundus examinations of the patients were carried out and the intraocular pressure values were measured with goldmann applanation tonometry ; those patients with ocular pathology were excluded from the study . before the eye examination ,\nfollowing the eye examinations , 45 minutes after the patients were given 1% cyclopentolate hcl drips 3 times with 5 minutes intervals , their auto - refractometry values were recorded again .\nthe intended purpose of using the cyclopentolate with mydriatic and cycloplegic effect was that with the cycloplegic effect , ciliary muscles contraction was hindered and refractivity of the lenses increases through cambering ; in other words , accommodation was hindered .\nthus , we aimed to provide more accurate refractivity values for the eye structures . in the study ,\nspherical equivalents ( se ) and cycloplegic spherical equivalents ( cse ) from the auto - refractometrical values of the patients were used .\nspherical equivalent is equal to the sum of the sphere value and half the cylindrical value , which were measured by the auto - refractometer device .\ndata were analyzed using spss ( statistical package for social sciences ) for windows 17.0 software . for quantitative data to compare the groups with normal distribution of parameters ,\nwe prospectively compared the patients who consulted the neurology policlinic between june 2013 and march 2014 with a headache complaint and diagnosed with migraine in accordance with the ichd-2 criterion with the individuals of the same gender and age group with no headache complaint .\nthis study adhered to the tenets of the declaration of helsinki and was carried out with the approval of the institution .\nthe patients were given full detailed eye examinations and findings were noted . out of these patients , those over age 18 years who had 20/20 uncorrected vision and who did not have ocular pathology in their examination were included in the study .\nthe patients were divided into 3 groups : group 1 : 86 eyes of 43 migraine patients without aura ; group 2 : 38 eyes of 19 migraine patients with aura ; and group 3 : 60 eyes of 30 patients without headache .\nthe corrected and uncorrected vision of right eye and left and bilateral eye of all the patients were individually measured .\nthose patients whose uncorrected vision did not have 20/20 value for both eyes separately and bilaterally were excluded from the study . the 3-dimensional vision and eye movements of the patients\nwere evaluated by the worth 4-point test and those patients who failed this test were excluded from the study .\nbiomicroscopic and fundus examinations of the patients were carried out and the intraocular pressure values were measured with goldmann applanation tonometry ; those patients with ocular pathology were excluded from the study . before the eye examination ,\n45 minutes after the patients were given 1% cyclopentolate hcl drips 3 times with 5 minutes intervals , their auto - refractometry values were recorded again .\nthe intended purpose of using the cyclopentolate with mydriatic and cycloplegic effect was that with the cycloplegic effect , ciliary muscles contraction was hindered and refractivity of the lenses increases through cambering ; in other words , accommodation was hindered .\nthus , we aimed to provide more accurate refractivity values for the eye structures . in the study ,\nspherical equivalents ( se ) and cycloplegic spherical equivalents ( cse ) from the auto - refractometrical values of the patients were used .\nspherical equivalent is equal to the sum of the sphere value and half the cylindrical value , which were measured by the auto - refractometer device .\ndata were analyzed using spss ( statistical package for social sciences ) for windows 17.0 software . for quantitative data to compare the groups with normal distribution of parameters ,\nforty - three ( 69% ) out of the total of 62 patients had migraine without aura and 19 of them ( 31% ) had aura migraine .\nage , gender distribution , and auto - refractometrical values of the migraine and control patients are given in table 1 .\nalthough the cycloplegic spherical equivalents results of the right eyes were not statistically significant , statistical significance was found in the tukey test between the migraine patients with aura and the control group ( p=0.05 ) .\nthe right and left eyes of the patients were evaluated together and a significant correlation was found between the groups . it was also found through the tukey test that the source of significance was patients with aura ( p=0.010 ) .\nwhen the refractive value differences between both eyes were evaluated , no significant difference was found in se and cse measurements ( p=0.411 and 0.536 ) . to evaluate\nthe impact of cycloplegia in patients , se and cse values were obtained and differences between these values were evaluated . in the post\nhoc tukey test , it was found that the change in group 2 patients was significantly lower than the change in group 3 patients ( p=0.024 ) .\nthe differences between cse and se in all eyes in both groups are given in table 3 .\nninety - nine percent of migraine patients with aura had visual symptoms . it was observed that since visual auras such as photopsy , scintillating scotoma , and hemianosmic changes in the foreground , especially in migraine with aura , the potential ocular problems in migraine pathogenesis have to be taken into account and the patients consulting with headaches were referred to ophthalmologists .\nwe give eye examination to the migraine patients referred to our policlinics from the department of neurology and evaluated their examination findings .\nthere are studies stating that migraine - related findings and refraction defects can trigger migraine .\nit was reported that migraine may impact the eyelids , conjunctiva , iris , pupil , optical nerve , retina , and extraocular muscles .\nthe relationship between the refractive errors and migraine has been researched since the beginning of the 20 century .\nalthough these studies especially emphasized that anisometropia and astigmatism were the triggers of migraine , the value of their results were limited because they were not controlled studies and no statistical evaluation was made [ 79 ] .\nemphasized that blurry vision generated by astigmatism could create a hyperexcitability on the visual cortex and this could be a triggering factor for migraine .\nwhen the migraine patients in our study were compared with the same age and gender groups , the spherical equivalents were found to be the same , but the cycloplegic spherical equivalents were significantly lower . when the migraine patients are divided into groups with and without aura and evaluated this way , while se values of the patient group with aura were similar to the control group , their cse values were significantly lower .\ncompatible with this finding , it was found that the changes in migraine patients with aura between the measurements before and after eye drops ( 1% cyclopentolate hcl ) were significantly lower .\nsimilar to our study , there are studies demonstrating that the refractive errors were not different in migraine patients and it was also suggested in these studies that binocular vision was important .\nhowever , even though we found no significant difference in refractive values between the 2 eyes in our study , all the patients involved in the study had 3-dimensional and uncorrected 20/20 vision .\nthe fact that the cycloplegic refraction values , especially in patients with aura , were found to be lower in comparison to healthy individuals could be an indication that these patients did not make sufficient accommodation .\nsince these patients could have blurry vision and difficulty focusing , it should be noted that this could be the trigger of a headache . on the other hand ,\nno anisocoria was found in any of our patients ; however , we failed to measure the pupil diameters since we did not have a pupillometer .\nit is possible that lack of accommodation in addition to isochoric and mydriatic pupils may create an attack with the increase in the amount of light entering the retina .\nit was found in the previous studies that visual stimulus triggered a migraine in more than 1/3 of the patients and that the migraines triggered by light decreased in patients who were given colored lenses during the migraine attack .\nbright light was a triggering factor in 87% of the migraine patients with aura , and this rate was 76% in migraine patients without aura .\nthe general characteristic of this condition is that with the third cranial nerve the most affected , it is accompanied by ocular cranial nerve palsy together with the migraine - like headaches in the form of attacks . in these situations ,\nin which the pathophysiology is not fully understood in 75% of the patients , there was contrast increase and thickening in the mri - scanned nerves during the attacks , and it was thought that there might be an accompanying migraine or independent neuropathy . in another study , in a spect - scanned nerve area ,\na low level of blood flow was detected and it was thought that a temporary ischemic attack might follow .\nin addition , ciliary ganglion cells or migraine - related elongated mydriasis might have occurred as a result of temporary dysfunctioning of postganglionic and parasympathetic fibers during a migraine attack .\nthe researchers who coined the term sillier ganglioplegic for this particular situation stated that this might be another result of ophthalmoplegic migraine pathogenesis . according to this hypothesis\n, the cause of ophthalmoplegic migraine may also cause elongated mydriasis by clinging to the parasympathetic fibers . in the same study , it was stated that , in theory , the pain stemming from the sillier ganglions may find its way to the ophthalmic region of the trigeminal nerve and may create a bilateral headache .\nbased on this study , it is possible to conclude that innervation deterioration in the sillier ganglions into the sillier muscle in these patients may cause insufficient accommodation .\nhowever , it was not possible to evaluate these hypotheses in our study since there were insufficient numbers of migraine patients with aura ; they were evaluated during the remission period and no mri tests were carried out .\nwe are of the opinion that the main causes of these conflicting results are misdiagnosis of headaches , changes in the diseases classification due to the new diagnostic techniques , evaluation of all the migraine patients together , and the lump - sum evaluation of all the eye impairments and visual levels .\nto keep our study free of such handicaps , we only evaluated the patient with uncorrected 20/20 vision , dividing them into groups with and without aura .\nwe found that the cycloplegic spherical equivalent values of our patients with aura were lower than in control patients .\nhowever , given the fact that our findings were obtained from the eye examinations of the patients during the remission period , it is not possible to determine whether migraine with aura is the trigger or the result of those attacks .\nhowever , the number of migraine patients with aura is less than those without aura and it is very difficult to detect by the patient s ophthalmologist during the attack period . in order to be more conclusive about this particular issue\n, the neurologist and ophthalmologist should be in communication and there is a need for more comprehensive studies with larger number of participants .", "answer": "backgroundthe aim of this study was to compare spherical equivalents ( se ) and spherical equivalents with cycloplegic ( cse ) values of migraine patients with and without visual aura , with those patients without migraine complaints.material/methodswe included patients over the age of 18 years , who had 20/20 uncorrected vision , and who did not have ocular pathology in their examination . \n the patients were divided into 3 groups : group 1 : 86 eyes of 43 migraine patients without aura , group 2 : 38 eyes of 19 migraine patients with aura , and group 3 : 60 eyes of 30 patients without migraine . \n spherical equivalents and spherical equivalents with cycloplegic from the auto - refractometrical values of the patients were compared.resultsthe mean age of the migraine and control patients was 34.28.3 and 33.610.8 years , respectively . \n forty - three ( 69% ) of 62 migraine patients had migraine without aura and 19 ( 31% ) had migraine with aura . \n the right and left eyes of the patients were evaluated together and a significant correlation was found between the groups . to evaluate \n the impact of cycloplegia in patients , se and cse values were obtained and differences between these values were evaluated . \n it was found that the change in group 2 patients was significantly lower than the change in group 3 patients ( p=0.024).conclusionswe found that the cycloplegic spherical equivalents values of our patients with aura were lower than control patients . \n we need further studies to reveal whether migraine with aura is the trigger or the result of those attacks .", "id": 38} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbecause many prenatal disorders involve more than one organ , an important clue of prenatal diagnosis is to look for multiple anomalies .\ntherefore , finding a specific lesion commands detailed examination of the fetus to rule out a possible involvement of other organs .\nthis approach is clinically important as identifying multiple lesions may impact on diagnosis , prognosis , and pregnancy / postnatal management .\nthe aim of the present work was to report on two cases in which digestive tract occlusion or perforation was found to be associated with brain hemorrhage . in one fetus , finding this association modified the prognosis and the outcome of pregnancy , while in the other , it influenced the postnatal management .\na 39yearold pregnant woman was referred to our multidisciplinary center of fetal medicine at 26 weeks of gestation for reevaluation of fetal intestinal dilatation and ascites .\nan amniocentesis performed at 21 weeks due to mother age was normal for a female fetus . on ultrasound ( us ) , a meconial pseudocyst in the left flank of the fetus , ascites , and slight bowel dilatation ( 7 mm ) were found ( fig .\nthe doppler study was normal for the umbilical artery and ductus venosus but it showed slight daily changes in the resistive index of the medial cerebral artery from 0.84 to 0.75 .\nperformed at 31 weeks , a sudden increase in bowel dilatation ( 15 mm ) was observed .\nthe mri performed on the next day , confirmed the presence of meconial pseudocyst , small bowel dilatation , and unused microcolon which likely developed in the context of perforation secondary to small bowel atresia .\nbecause the mri reference scan showed an abnormal hyperintense t1 cerebral lesion , a focused brain mri was performed the week after , at 32 weeks .\nthis examination demonstrated intraventricular hemorrhage and extensive intraparenchymal frontoparietal ischemic lesions , consistent with the diagnosis of grade 4 brain hemorrhage ( fig .\nthese lesions had most probably been overlooked at least on the us scan performed on the day before the first mri . a 26week and 4day axial us abdominal scan of the fetus 1 showing the meconial pseudocyst ( between crosses ) and the ascites ( arrow ) . a 31week t2 weighted mri coronal slice of the brain of the same fetus showing the periventricular parenchymal ischemic lesions ( arrow ) , the hemosiderin deposits in the subependymal region ( arrow head ) , and the ex vacuo dilatation of the frontal horn of the lateral ventricle : grade 4 hemorrhage .\nafter multidisciplinary discussion and complete information of the parents , they elected termination of pregnancy at 34 weeks because of the risk of cerebral palsy and poor abdominal prognosis .\na 25yearold pregnant woman came to our fetal medicine center for routine second trimester us at 22 weeks .\nthe amniocentesis revealed neither genetic anomalies nor infection . on subsequent us performed at 25 weeks , an intraventricular brain hemorrhage ( fig .\n, we observed a progressive dilatation of the bowel loops and resolution of the effusions .\nthe colon that should be clearly visible on third trimester us was never seen suggesting proximal bowel atresia .\na comprehensive mri performed at 31 weeks investigated both regions , the fetal brain mri confirmed the grade 2 hemorrhage without parenchymal lesions and the abdominal mr sequences demonstrated a distal small bowel atresia with unused microcolon ( fig .\nthe loops dilatation increased to 30 mm diameter with heterogeneous content and slight abdominal effusion suggesting parietal damage .\na caesarian delivery was performed on the same day giving birth to a 2620 g baby girl with good apgar score .\nthe neonatal surgery confirmed an isolated distal small bowel atresia , with proximal intact loops , the atretic segment was resected , and a double ileostomy was done .\na 25week axial us scan of the head of the fetus 2 showing subependymal hemorrhage ( arrow ) and the hyperechogenic wall of the lateral ventricle ( arrow head ) : grade 2 hemorrhage .\na 31week t2 weighted mri coronal scan of the fetus 2 showing normal fluid filled proximal loops ( arrow ) and dilated intermediate and distal loops attesting of the distal small bowel occlusion .\nwe report on two cases of prenatal diagnosis of digestive tract occlusion or perforation that were found to be associated with brain hemorrhage ; this significantly impacted on prognosis in one case and on postnatal management in the other .\ndifferent theories have been proposed to explain digestive tract atresia : for example , lack of vacuolization of the solid cord stage of intestinal development or ischemic insult to the midgut due to mesenteric vascular accident 1 , 2 .\nthe atresia can be isolated but may also be associated with meconium ileus , apple peel atresia , volvulus , or abdominal wall defect 3 , 4 .\ncystic fibrosis should be excluded as it is an associated condition in 740% of cases 5 , 6 .\nconcomitant extraintestinal anomalies are less frequent , though one study reported extra abdominal malformations like congenital heart disease , down 's syndrome , anorectal and vertebral anomalies , neural tube defect , microcephaly , and vesicoureteral reflux 7 . to our knowledge , the association of meconial peritonitis or ileal atresia with brain hemorrhage has never been described prenatally .\na vascular insult responsible of the gut atresia could be associated with blood flow disturbance leading to cerebral hypoperfusion and subsequent injury 8 , 9 . in case 1 ,\nthe appearance of the brain ischemic lesion on mri at 31 weeks was compatible with vascular insult going back to a few weeks earlier .\nexperimental studies in fetal sheep 10 have shown that cerebrovascular immaturity may impair the ability to maintain constant cerebral blood flow over a wide range of changes in arterial blood pressure ; this might also apply to human foetuses .\nperiventricular and subependymal regions that corresponded to the affected zones in our two fetuses are of greater susceptibility because of high metabolism and watershed vascular regions 11 .\nanother hypothesis explaining the rare association of meconial peritonitis and brain hemorrhage may be an intravascular meconial dissemination leading to endovascular occlusions by squamous cells\n. a neonatal case has been published associating meconium peritonitis , periventricular leukomalacia , and pulmonary hypertension leading to neonatal death secondary to respiratory insufficiency .\nnecropsy disclosed disseminated intravascular occlusions by squamous cells 12 . a case of twintotwin transfusion syndrome has also been reported ; one twin presented meconium peritonitis and intravascular disseminated coagulation that led to intrauterine death of the other twin .\nthese two possible pathogenic mechanisms could cause vascular disruption of the blood supply in multiple organs and hence explain the association we describe in the present report .\nthese two rare cases associating digestive tract occlusion or perforation and brain hemorrhage give us the opportunity to emphasize the need for careful screening of the fetal brain in such acute abdominal conditions . because brain lesions may be delayed , neonatologists and pediatricians should also be vigilant and prescribe transfontanellar us whenever a newborn has a history of bowel ischemia and/or perforation .", "answer": "key clinical messagewe report two prenatal cases of an exceptional association of digestive tract atresia or perforation with brain hemorrhage . \n this combination worsens the prognosis leading to termination of pregnancy in one case . \n we outline the importance of a careful fetal brain examination on imaging in cases of prenatal acute abdominal insults .", "id": 39} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nduring 20042007 , as part of a broader biodiversity survey and inventory program , we sampled birds from mostly forested sites in guangxi and guizhou provinces in the southern part of the people s republic of china ( figure ) .\nsampling was conducted by mist netting and selective harvesting with shotguns ; all birds in the study were apparently healthy and behaving normally at the time of collection . because initial sampling was focused on endoparasite communities , samples from 20042005 consisted of complete gastrointestinal tracts frozen in liquid nitrogen . in 20062007\nsoutheastern asia , showing 5 sites in the people s republic of china where land birds were collected and tested for influenza a virus .\nprevalence values were 4% ( n = 103 ) in dashahe in 2006 ; 6% ( n = 194 ) in kuan kuoshui in 2006 ; 0.3% ( n = 328 ) in shuipu in 2007 ; 3% ( n = 184 ) in jing xi , in 2004 ; and 0% ( n = 130 ) in shiwandashan in 2005 .\na total of 184 samples were collected from jing xi municipality in guangxi ( 21.122n , 105.964e ) in 2004 , 130 from shiwandashan nature reserve in guangxi ( 21.840n , 107.880e ) in 2005 , 103 from dashahe nature reserve in guizhou ( 29.167n , 107.575e ) in 2006 , 194 from kuan kuoshui nature reserve in guizhou ( 28.226n , 107.160e ) in 2006 , and 328 from shuipu village , guizhou province ( 25.485n , 107.882e ) in 2007 ( figure ) .\nsamples were tested for influenza a virus by real - time reverse transcription pcr ( 6 ) in 2 diagnostic laboratories ( southeast poultry research laboratory , us department of agriculture , athens , ga , usa , and national wildlife health center , us geological survey , madison , wi , usa ) .\nof 939 samples tested , 24 were positive for influenza a viruses ( prevalence 2.3% , table ; complete summary in appendix table ) .\nif migratory behavior ( species classified as migratory or nonmigratory on the basis of descriptions by mackinnon and phillipps ) , was considered , 11 ( 4.8% ) of 231 samples from species showing marked seasonal migrations were influenza positive .\nhowever , only 13 ( 1.8% ) of 708 samples from nonmigratory species were positive .\nthe cumulative binomial probability that such a high number ( 11 ) of positive samples would result among the 231 migratory - species samples , were the true prevalence to be 1.8% , is low ( p = 0.0013 ) .\nthus , migratory species appear to have higher influenza infection rates . in terms of general habitat use ( 7 ) , open - country species were slightly more prone to be influenza positive ( 8 [ 2.9% ] of 274 samples ) than forest species ( 16 [ 2.4% ] of 665 samples ) , but the difference was not significant ( cumulative binomial probability , p>0.05 ) .\ninteractions between migratory behavior and habitat use were not significant ( contingency test , p>0.05 ) .\nalthough all infections detected were among songbirds ( passeriformes ) , the sampling also concentrated on songbirds ( 94.3% ) .\nthus , we could not test adequately the hypothesis that influenza prevalence was equivalent between songbirds and other birds .\nan obvious question is whether the influenza a viruses we detected belong to the highly pathogenic subtype h5n1 strain currently circulating across much of asia .\npcr ( 6 ) , although this result does not exclude the possibility that h5 viruses were among the positive samples .\nthe preservation status of samples we tested prevented virus isolation or full , strain - level characterization of influenza viruses .\nthe subtype h5n1 strain of influenza virus has spread rapidly and has been detected across much of central and southern eurasia . although movements of wild birds have been implicated in this spread ( 8) , other studies question ( 9,10 ) or contradict ( 11 ) this idea .\nan important part of the argument centers on the question of the occurrence of the virus in wild birds without obvious illness , which can be difficult to interpret given the low prevalence of influenza .\nfor instance , a recent study based on sampling > 13,000 migratory birds in china detected the subtype h5n1 strain of influenza virus only 8 times ( 12 ) , and similar results have been obtained elsewhere ( 2 ) .\nour study , although not successful in characterizing influenza viruses to specific strains , nonetheless shows that influenza a virus infection occurs in more bird species than previously assumed and that influenza a infections can be found in birds that behave normally and show no sign of illness .\nalthough a review of avian influenza virus ecology ( 1 ) discussed the occurrence of influenza viruses across all groups of birds ( and other vertebrates ) , subsequent studies have assumed that waterbirds are the primary reservoir ( 8,13,14 ) . in this study ,\nalthough waterbirds could have higher prevalences , we have demonstrated broad occurrence of influenza viruses in diverse taxa of passeriformes ( songbirds ) in southeast asia .\nthis result suggests that land birds may also be a major reservoir of influenza viruses .\nwe have taken a step toward a more complete understanding of influenza virus ecology among wild birds .\nour partial survey of influenza virus distributions across the rich avifaunas of the southern region of china demonstrated frequent infections .\nwe suggest that to be effective future surveillance efforts will need to include the full diversity of wild birds .", "answer": "water birds are considered the reservoir for avian influenza viruses . \n we examined this assumption by sampling and real - time reverse transcription \n pcr testing of 939 asian land birds of 153 species . \n influenza a infection was found , particularly among migratory species . \n surveillance programs for monitoring spread of these viruses need to be redesigned .", "id": 40} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchronic suppurative otitis media ( csom ) is an inflammatory disease of the middle ear and mastoid air cell system , which can result in irreversible changes not only in the middle ear structures but also in the inner ear.1 ) dysfunction of the eustachian tube and the bacterial infection are important factors in the multifactorial pathogenesis of csom . in order to eradicate inflammation ,\nprevent recurrence and restore middle ear structures and hearing , both medical and surgical treatment modalities are important in csom .\nit has been emphasized that selection of appropriate antibiotics should be based on the bacteriologic studies to identify the pathogens and determine sensitivities.2,3 ) recent bacteriologic studies of the middle ear discharge in csom in korea have reported increasing prevalence of methicillin - resistant staphylococcus aureus ( mrsa).2,4,5 ) in addition , staphylococcus aureus ( s. aureus ) and pseudomonas species were most predominant from the postoperative otorrhea cultures.3 ) higher rates of postoperative otorrhea and reperforation after tympanomastoid surgeries were reported in csom patients with mrsa cultured from preoperative ear discharge.6 ) in addition to intrinsic mrsa infection of the mastoid air cell system , nasal colonization of mrsa may pose increased risk of postoperative infection . nasal colonization rate of mrsa and it is a known predictor of postoperative surgical site infection.7,8 ) previous studies have identified bacterial pathogens from the middle ear and the mastoid air cells , or nasopharynx as a bacterial reservoir in csom.4,5,9 - 12 ) however , few studies have focused on the effect of nasal mrsa colonization in the otologic surgery .\nthe aims of this study are to examine the prevalence of nasal mrsa colonization in patients undergoing otologic surgeries and to determine the association between mrsa colonization and the pathogens identified from perioperative culture studies .\nthe study included 66 consecutive patients ( 25 males and 41 females ) undergoing tympanomastoid surgeries from may 2010 to december 2011 at the yonsei university college of medicine gangnam severance hospital .\npatients with intracranial or extratemporal complications of csom , known history of external radiation , known history of corticosteroid therapy preoperatively , or those undergoing emergency operations were excluded .\nthe mean age at operation was 51.715.7 years ( range 34 - 74 years ) , and the right ear was operated in 34 ears , the left in 32 ears . upon the initial visit in the outpatient department , the external auditory canal was cleaned , and the middle ear discharge was collected with collected with cotton swabs through sterile otoscopes , taking care not to touch the external auditory canal skin . to assess nasal colonization of s. aureus ,\nthe nasal samples were obtained by cotton swab from the anterior vestibular of the nares by the physician . during the operation , intraoperative culture specimens were taken in cases with overt discharge in the middle ear cavity . during postoperative period of 1 month ,\npostoperative culture specimens were again taken in cases with otorrhea through the external auditory canal .\nall culture samples were in stuart transport medium and transported to the laboratory , where the samples were inoculated onto blood agar , macconkey 's agar , and chocolate agar plates .\nall plates were incubated at 37-c aerobically under 5% ( v / v ) co2 and examined 24 and 48 hours later .\nsusceptibility testing was performed using disk diffusion . identified pathogen species and antimicrobial susceptibility were compared between nasal swab and perioperative ( preoperative , intraoperative and postoperative otorrhea ) cultures .\nstatistical analysis was performed with fisher 's exact testusing spss statistical software ( version 15.0 ; spss inc . ,\namong the 67 patients undergoing operation for csom , nasal swab confirmed bacterial colonization in 37 ( 55.2% ) patients ( table 1 ) . clinically importantly , nasal cavity colonization of s. aureus was noted in 10/67 ( 14.9% ) of patients , and 4/67 ( 6.0% ) patients were positive for mrsa .\nalso , methicillin - sensitive staphylococcus aureus ( mssa ) was identified in 9/37 ( 23.4% ) and methicillin - resistant coagulase - negative staphylococcus ( mrcns ) in 11/67 ( 13.4% ) of patients .\npreoperative ear culture studies identified pathogens in 39/67 ( 58.2% ) of the patients : the most commonly identified species was staphylococcus [ mrcns 26.9% , methicillin - sensitive coagulase - negative staphylococcus ( mscns ) 1.5% , mrsa 13.4% and mssa 11.9% ] .\nmrsa was found in 3/40 ( 4.5% ) ears , mssa in 2 ears ( 3.0% ) , mrcns in 2 ears ( 3.0% ) and mscns in 1 ear ( 1.5% ) .\nafter the surgery , 11 of the 67 patients developed otorrhea within 1 month postoperatively .\nthe postoperative culture studies identified mrsa in 3/11 ( 27.3% ) and acinetobacter species in 1/11 ( 9.1% ) and fungus in 2/11 ( 18.1% ) patients ( table 2 ) .\npreoperative ear culture results and nasal swab culture results showed significant difference ( p=0.001 ) , as well as intraoperative middle ear cultures and postoperative otorrhea culture results showed significant difference ( p=0.023 ) .\nhowever , no significant difference was noted between preoperative ear and postoperative otorrhea culture results ( p=0.493 ) .\nthen we compared the culture results according to the presence of bacterial growth and reports of no growth ( fig .\nno significant difference was noted between preoperative ear culture , and nasal swab culture results ( p=0.055 ) , between preoperative ear and postoperative otorrhea culture results ( p=0.068 ) , or nasal swab and postoperative otorrhea culture results ( p=0.094 ) .\nlastly , the culture results were compared according to the presence of antibiotic resistance ( fig .\nno significant difference was noted between the antibiotic - susceptible and resistant strains identified between preoperative ear culture and nasal swab cultures ( p=0.098 ) , or between preoperative ear and postoperative otorrhea cultures ( p=0.053 ) .\nthen we analyzed the correlation of isolated organisms from the nasal swab and other cultures in patients with nasal colonization of antibiotic - resistant strains ( fig .\n4 ) . among 4 patients with identified with nasal mrsa colonization , preoperative ear cultures were also positive for mrsa in 3 patients ( 75.0% ) .\nhowever , intraoperative culture identified mrsa in only one patient , and none of the patients developed mrsa infection postoperatively .\npreoperative ear cultures reported mrsa in 1 , mrcns in 1 , and mscns in 7 , ciprobay - resistant pseudomonas in 1 , and no growth in 2 patients .\nincreasing incidence of antibiotic - resistant bacterial strains in csom patients poses a challenge to not only the selection of appropriate antibiotics therapy , but also to prevent the emergence of resistance to glycopeptides , the main drugs chosen for mrsa .\nit has been reported that patients who are colonized with s. aureus are the main source of s. aureus in hospitals , and that nasal carriage of mrsa increases the risk of postoperative infection . since the rate of methicillin resistance is higher in korean csom patients compared to other countries , we examined the rate of nasal mrsa colonization .\nthe rate of nasal carriage of mrsa in csom patients was higher than among healthy individuals reported as 0.2 - 2.8% of the united states population.7 ) although this study was limited to small number of patients , the finding may suggest that in addition to nosocomial infection , community - acquired mrsa infection may contribute partially to the relatively higher rate of mrsa in csom patients in korea . on the other hand ,\nthe rates of bacterial isolation from preoperative ear discharge , intraoperative middle ear discharge , or postoperative otorrhea cultures in our patients were lower .\nalso , the perioperative culture studies frequently reported no growth of pathogens . given that the patients were prescribed with antibiotics prior to surgery , it may signify that current antibiotics are effective in infection control during the tympanomastoid surgery . furthermore , the interpretation of the culture results from postoperative otorrhea is limited since antibiotics were routinely used postoperatively in all patients and culture samples were taken from the external auditory canal in cases with overt otorrhea or from wet surface of the grafted tympanic membrane immediately after removal of the packing material at 2 weeks postoperatively . the culture results can only reflect that mrsa infection that could not be controlled by routine antibiotics , which may be clinically significant .\nmrsa has been identified not only in csom patients,2,3,5,13 ) but also in patients with external otitis.14 ) \n s. aureus has been implicated in biofilm formation complicating cochlear implants.15 - 17 ) nasal mrsa colonization deserves attention since transmission from nasal carriage to surgical site infections or bacteremia is possible , and it is associated with increased morbidity and mortality .\nprevious studies have reported that elimination of nasal mrsa colonization reduces the risk of postoperative infections.8,18,19 ) application of 2% mupirocin calcium ointment to the nares has been proven to be effective , and chlorhexidine - based solutions is used to reduce the density of skin colonization of mrsa preoperatively.18 - 20 ) a recent study compared the rates of mrsa infection in otolaryngology surgeries , before and after implementation of preoperative screening and treatment of nasal mrsa carriage.21 ) further studies are warranted to investigate the possible benefit of preoperative treatment of mrsa colonized patients undergoing middle ear surgeries .\nthe rate of nasal mrsa colonization among patients with csom was higher than among the general community .\nfurther studies are warranted to investigate the possible benefit of preoperative treatment of mrsa colonized patients undergoing middle ear surgeries .", "answer": "background and objectivesmethicillin - resistant staphylococcus aureus ( mrsa ) is one of major pathogens in patients with chronic suppurative otitis media ( csom ) . \n in addition to intrinsic mrsa infection of the mastoid air cell system , nasal colonization of mrsa , a known predictor of postoperative surgical site infection , may pose increased risk of postoperative complications . \n the purpose of this study is to describe microbiology of preoperative nasal swab screening and localized middle ear specimens in patients undergoing otologic surgeries.subjects and methodsforty - nine consecutive patients with csom who underwent middle ear surgery were included . \n preoperative nasal swabs for mrsa , and preoperative and intraoperative middle ear swabs were collected and compared for pathogens.resultspreoperative nasal swab screening confirmed mrsa colonization in 3/49 patients ( 6.1% ) and methicillin - resistant coagulase - negative staphylococcus ( mrcns ) in 9/49 patients ( 18.4% ) . \n correlation with preoperative culture results and nasal swab screening results were compatible in 2/4 patients with positive nasal swab for mrsa and 1/9 patients with positive nasal swab for mrcns . \n postoperative conversion to mrsa was observed in 3 patients.conclusionsthe rate of nasal mrsa colonization among patients with csom was higher than among the general community . \n preoperative mrsa colonization was associated with mrsa from middle ear specimens . \n further studies are warranted to investigate the possible benefit of preoperative treatment of mrsa colonized patients undergoing middle ear surgeries .", "id": 41} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe patients in the african - heritage ( n = 9 ) and caucasian - heritage ( n = 11 ) groups had similar distributions of sex , age , and duration of diabetes ( male 75 vs. 70% , p = 0.89 ; mean sd age 53.3 7.2 vs. 55.2 4.6 years , p = 0.50 ; and duration 10.3 10.7 vs. 6.8 6.4 years , p = 0.37 , respectively ) .\nsystolic blood pressure and diastolic blood pressure were 124.4 vs. 122.1 mmhg ( p = 0.75 ) and 77.0 vs. 76.1 mmhg ( p = 0.81 ) , respectively .\nthe patients were nave to antihypertensive therapy , and equal numbers in each group received metformin ( n = 6 ) and insulin ( n = 2 ) .\na1c and urinary albumin were measured by high - pressure liquid chromatography ( ha 8 - 121 ; biomen , berkshire , u.k . ) and immunoturbidimetry , respectively .\nmicroalbuminuria was excluded on the basis of three consecutive albumin - to - creatinine ratios <3 mg / mmol in sterile , early - morning urine samples and a urinary albumin excretion rate < 30 mg / day .\nrenal plasma flow ( rpf ) was measured by the constant infusion method ( 6,7 ) .\na bolus dose of 8 mg / kg paraminohippurate ( merck , sharp & dohme , hoddesdon , u.k . ) was given with a 20 mg / min infusion .\nafter a 90-min equilibration period , the concentration of the infusate was multiplied by the infusion flow rate and divided by the mean of duplicate plasma samples at this and subsequent time points .\nplasma paraminohippurate was assayed after deproteinizing the samples with 6% trichloroacetic acid for 10 min at 70c and sequentially adding sodium nitrite , ammonium sulfamate , and n-1-naphthylethylenediamine using a cobas mira ( roche , lewes , u.k . ) .\nafter initial equilibration , an amino acid mixture ( vamin ; pharamcia & upjohn , milton keynes , u.k . ) was infused ( 0.043 ml kg min ) .\nrpf was assessed 80 min later , and then l - nmma ( clinalfa , laufelfingen , switzerland ) was begun at the nonpressor dose of 20 g kg min .\nboth infusions were continued for a further 20 min , after which a final rpf measurement was made . during the studies ,\nblood pressure was monitored automatically ( dinamap ; critikon , basingstoke , u.k . ) , and whole blood was sampled from a venflon in a hand vein to measure glucose by the oxidase method ( one touch ; lifescan , high wycombe , u.k . ) every 10 min .\nmean arterial pressure ( map ) was calculated as the diastolic blood pressure plus one - third of the pulse pressure .\nrenal blood flow ( rbf ) was calculated by dividing the rpf by 1 hematocrit and renal vascular resistance ( rvr ) by dividing map by rbf .\nthe study was approved by the ethics committee of the whittington hospital national health service trust .\nanalyses between or within the groups were performed using spss for windows ( version 10 ; spss , chicago , il ) .\ncontinuous variables were compared with parametric or nonparametric tests and associations tested with spearman 's rank correlation test or pearson 's x test according to their distribution .\ncategorical variables were compared using a test with continuity correction or fisher 's exact test .\nclearance and rpf measurements were corrected for a body surface area of 1.73 m. data are expressed as means sd unless otherwise stated .\nanalyses between or within the groups were performed using spss for windows ( version 10 ; spss , chicago , il ) .\ncontinuous variables were compared with parametric or nonparametric tests and associations tested with spearman 's rank correlation test or pearson 's x test according to their distribution .\ncategorical variables were compared using a test with continuity correction or fisher 's exact test .\nclearance and rpf measurements were corrected for a body surface area of 1.73 m. data are expressed as means sd unless otherwise stated .\ncomparative baseline measurements of rpf and systolic and diastolic blood pressures were similar between the african - heritage and caucasian - heritage groups ( rpf 533.7 174.7 vs. 565.3 260.8 ml / min per 1.73 m , p = 0.78 ; systolic 124.9 23.7 vs. 121.6 12.3 mmhg , p = 0.29 ; and diastolic 77.1 9.5 vs. 76.3 5.7 mmhg , p = 0.81 , respectively ) .\nthere were no differences in creatinine clearance or median urinary albumin excretion rate ( 93.7 19.9 vs. 98.9 19.5 ml / min per 1.73 m , p = 0.57 , and 12.6 [ 4.125.0 ] vs. 14.0 [ interquartile range 8.524.1 ] mg / day , p = 0.79 ) .\naveraged blood glucose was similar ( 6.7 0.9 vs. 7.4 0.9 mmol / l ; p = 0.14 ) .\na1c was lower in the african - heritage than in the caucasian - heritage group ( 6.8 0.69 vs. 8.0 0.94% ; p = 0.005 ) .\nthe l - nmma infusion was associated with significant changes in systolic blood pressure in the african - heritage group ( fig .\nrelative to the baseline and post amino acid measurements , there was a mean rise of 10.0 mmhg ( 95% ci 2.317.9 ; p = 0.017 ) and 7.3 mmhg ( 1.013.7 ; p = 0.03 ) , respectively , in the african - heritage group and 4.3 mmhg ( 1.8 to 10.4 ; p = 0.23 ) and 2.4 mmhg ( 3.5 to 8.3 ; p = 0.38 ) in the caucasian - heritage group .\nfinal blood pressure was higher in the african - heritage group ( 137.5 9.0 vs. 123.4 14.2 mmhg ; p < 0.05 ) and was associated with a fall in rbf ( 46.0 ml / min per 1.73 m ; p < 0.05 ) and a rise in rvr ( from 0.12 0.06 to 0.14 0.04 mmhg ml / min per 1.73 m ; p = 0.036 ) .\nthe changes in rvr correlated with map ( r = 0.77 ; p = 0.004 ) .\nin this study , patients without hypertension or renal disease of african heritage had an increased sensitivity to the renal vasoconstrictive effect of no synthase ( nos ) inhibition .\nthese data suggest that a reduction in no bioavailability may adversely affect autoregulatory processes that could potentially increase vulnerability to renal damage ( 8) .\nwe used the amino acid infusion to optimize renal blood flow and suppress tubuloglomerular feedback as a contributor to vasoconstriction .\ntherefore , the reduction in renal blood flow that we observed was probably due to an effect of nos inhibition on the renovascular smooth muscle .\nearly in the course of diabetes , no production is necessary to forestall a rise in blood pressure .\nhypertension is associated with the generation of no - quenching free radicals and is a prerequisite for the development of renal disease ( 1012 ) .\nfurthermore , the renal expression of nos in patients with diabetes is related to the degree of vasculopathy ( 13 ) .\nit could therefore be considered that upregulation of no production in patients of african heritage is related to a mechanism that opposes an enhanced vasoconstrictor tendency .\nalthough consistent with experimental studies , these outcomes require caution before being generalized . confirmatory studies in patients with and without diabetes with greater power and the evaluation of the role of vasoconstrictive cytokines , angiotensin", "answer": "objective we compared the renal and systemic vascular ( renovascular ) response to a reduction of bioavailable nitric oxide ( no ) in type 2 diabetic patients without nephropathy and of african and caucasian heritage.research design and methods under euglycemic conditions , renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of l-ng-monomethyl-l-arginine.resultsin the african - heritage group , there was a significant fall in renal blood flow ( 46.0 ml / min per 1.73 m2 ; p < 0.05 ) and rise in systolic blood pressure ( 10.0 mmhg [ 95% ci 2.317.9 ] ; p = 0.017 ) , which correlated with an increase in renal vascular resistance ( r2 = 0.77 ; p = 0.004).conclusions the renal vasoconstrictive response associated with no synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of african heritage .", "id": 42} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na retrospective chart review was performed for cases of infectious scleritis seen from january 2007 to august 2011 .\nthe diagnostic criteria for a case of infectious scleritis included the presence of single or multiple inflamed anterior scleral nodules or ulcerations , which revealed a causative organism on microbiological culture .\nmicrobial cultures were considered significant if growth of the same organism was present on more than one solid medium or if there was a confluent growth on inoculation on one solid medium or if growth of one medium was consistent with direct microscopy findings .\ndata regarding patient demographics , predisposing factors , causative organisms , and clinical features for all 12 patients was extracted .\nall patients except one were followed up for a period of at least 6 months and , therefore , the treatment and outcome details were analyzed for 11 patients .\ndata was analyzed by the chi - square test using spss version 11.0.1 to determine the prognostic factors .\ntwelve eyes of 12 patients were identified to have culture - positive infectious scleritis . demographic data and clinical features\npreceding surgical procedures performed included manual small - incision cataract surgery ( 4 ) , pterygium excision ( 1 ) , and trabeculectomy ( 1 ) .\nnone of the patients had a history of fever , joint pain , respiratory illness , skin rashes , etc .\n, one patient ( case 2 ) had progeria , another had chronic liver disease ( case 6 ) , and 2 patients had diabetes ( case 8 and 10 ) .\npatients with multifocal scleritis were associated with growth of either gram - negative bacilli ( gnb ) or nocardia on culture an example of which is shown in fig .\n2a and b. demographics , clinical features , organisms , management , and outcomes of infectious scleritis ( a ) multifocal scleral abscesses owing to pseudomonas sp .\n( b ) healed scleritis with minimal scleral thinning 2 months after treatment with topical fortified antibiotics and dexamethasone ( case 11 ) ( a ) nocardia asteroides : gram stain showing filamentous forms fragmented into bacillary and coccoid forms ( magnification = 1000 ) .\n( b ) nocardia asteroides : orange coloured , centrally heaped , dry colony all patients received topical antimicrobials based on the culture and sensitivity report .\nseven patients were also treated with topical steroids due to severe intra - ocular inflammation .\nin addition to medical treatment , 5 patients underwent various surgical procedures in an attempt to decrease the load of infective organism or to preserve the globe as shown in table 1 and fig .\nof these , only 2 patients had a good final visual acuity ( better than 6/18 ) on the last follow - up visit .\nsix months after corneo - scleral patch graft following infectious scleritis post - cataract surgery ( case 8) we determined the prognostic factors of infectious scleritis using the chi - square test .\na poor visual acuity at presentation ( less than counting fingers at 1 m ) usually resulted in a worse visual outcome ( p = 0.005 ) .\nthe causes of poor visual acuity at last follow - up include corneal scarring following keratitis ( 1 ) , failed corneal graft ( 1 ) , secondary angle closure glaucoma and optic atrophy ( 1 ) , choroidal detachment ( 1 ) , and endophthalmitis ( 5 ) .\nthe visual outcome was not dependant on any particular organism ( p = 0.099 ) or the presence of multifocal abscesses ( p = 0.209 ) .\nthe addition of surgical intervention did not result in a significantly better visual outcome than medical management alone ( p = 0.209 ) , but resulted in a higher rate of globe preservation ( p = 0.045 ) .\na clinical suspicion of infectious scleritis in all cases of scleral inflammation following trauma has been emphasized previously .\nhowever , in our series , 4 cases were preceded by cataract surgery and only 1 by pterygium surgery .\nanother case series of indian eyes also showed maximum number of their cases had cataract surgery prior to an episode of infectious scleritis .\nthis may be due to the large number of scleral - tunnel small incision cataract surgeries performed in india as compared to clear corneal phacoemulsification performed in developed countries .\npseudomonas aeruginosa is the leading cause of microbial scleritis in reported literature . in our series , 33.33% had gnb , 25% had nocardia , and 25% had fungal infection .\none of the fungi was identified to be rhodotorula spp , which we have reported elsewhere . in cases of scleritis following trauma\nwhere infection is suspected but routine microbial culture is negative , polymerase chain reaction tests may be used to confirm the diagnosis .\nif these tests are also negative , the possible diagnosis of surgically induced necrotizing scleritis ( sins ) should be considered .\nsins is a believed to be a delayed - type hypersensitivity response to any form of surgical trauma . up to 90% of patients who develop sins\nmay have an undiagnosed systemic vasculitis and , therefore , a detailed systemic investigation is warranted .\nthis is often seen as late as 9 months after the surgical intervention and , after ruling out an infectious cause , requires treatment with intensive systemic immunosuppression .\nwhen infectious scleritis occurs long after surgery , it has been hypothesized to be due to an underlying sins with secondary microbial infection , which can make diagnosis and treatment difficult .\nthese patients may benefit from a systemic evaluation to rule out an autoimmune vasculitis , which will require appropriate management .\nsome presented with scleritis and developed secondary intraocular spread , which has been described in other reports .\nothers had scleritis , uveitis , and endophthalmitis at presentation ( e.g. , case 7 where the sclera in the area of the bleb was necrotic with vitreous inflammation ) . the wide use of anti - metabolites at the time of trabeculectomy increases risk of scleral melt and inflammation , which may have resulted in secondary infection and endophthalmitis .\npseudomonas is most often associated with this presentation , which has been attributed to an intra - scleral dissemination facilitated by its proteolytic products and motility .\nour series had 6 cases of multifocal scleral abscesses , 3 of which were due to p. aeruginosa , 2 due to nocardia , and 1 due to klebsiella sp .\na review of past literature suggests that multifocal scleritis can be caused by several organisms and may be related to factors such as the load of infection , rather than specific organisms .\nthe visual acuity at presentation is the most important prognostic factor determining the final visual acuity , and this has been seen in other studies .\nthis suggests that early diagnosis should help preserve the patient 's remaining vision if effective treatment is initiated .\nthere is a lot of discrepancy among researchers regarding the effect of surgical debridement on the outcome of infectious scleritis .\na large series showed that despite adjuvant surgery in 46 of 56 eyes , approximately 50% lost functional vision .\nhowever , unlike other studies , we did not find any difference in the final vision between the medically and surgically treated groups . in conclusion ,\nmanual small incision cataract surgery is a common predisposing factor to infectious scleritis in developing countries .\nthe visual acuity at presentation is the most important prognostic factor determining the final visual outcome .\naggressive surgical intervention improves the chance of globe preservation but does not improve the visual outcome .", "answer": "in this retrospective case series , we studied the predisposing factors , causative organisms , clinical spectrum , and outcomes of 12 cases of culture - proven infectious scleritis . \n nine of 12 patients had a history of preceding trauma ( surgical or accidental ) . \n past surgical history included small - incision cataract surgery ( 4 ) , pterygium surgery ( 1 ) , and trabeculectomy ( 1 ) . \n six patients had multifocal scleral abscesses due to pseudomonas , klebsiella , or nocardia . only 2 patients retained useful vision ( > 6/18 ) . a poor visual acuity at presentation usually resulted in a worse visual outcome ( p = 0.005 ) . \n four eyes developed phthisis . \n the addition of surgical intervention did not result in a significantly better visual outcome than medical management alone ( p = 0.209 ) , but resulted in a higher globe preservation rate ( p = 0.045 ) . \n therefore , we concluded that infection must be ruled out in cases of scleritis with preceding history of trauma , and aggressive surgical intervention improves the anatomical outcome but does not change the visual outcome .", "id": 43} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntransportation planning and public health have important historical connections . in the early 20th century transportation planning and public health\nheld similar objectives . in 1909 marsh wrote , city planning is the adaptation of a city to its proper function .\nthis conception can be indefinitely expanded but its significance will be appreciated if we admit that no city is more healthy than the highest death rate in any ward or block and that no city is more beautiful than its most unsightly tenement ( p.27 ) . since the early 20th century , the relationship between transportation planning and public health has waxed and waned [ 1 , 3 ] .\nthere is growing recognition that integration of theories and methods from each discipline is beneficial for advancing research and practice . \nof particular relevance to both transportation planning and public health are injuries due to traffic collisions .\nworldwide , traffic collisions are one of the leading causes of death among youth and young adults .\na number of intervention strategies including black spot analyses are used in transportation planning to reduce road fatalities .\nthere is ongoing debate in the transportation planning literature that this type of intervention may have limited effectiveness in reducing road fatalities [ 68 ] .\nnew approaches are needed to reduce the burden of road traffic fatalities . given the need to reconnect transportation planning and public health , this paper will present rose 's strategy of preventive medicine [ 9 , 10 ] , a promising intervention approach from public health .\nthe prevention paradox states that a preventive measure which brings much benefit to the population offers little to each participating individual ( p.38 ) .\nthe prevention paradox is based on an important distinction between an individual case and the incidence of cases in a population .\na case is defined as an episode of disorder , illness , or injury affecting an individual , while incidence is defined as \nthe number of cases of a disease that come into being during a specific time period ( p.44 ) .\nthe basic principle of geoffrey rose 's strategy of preventive medicine is that the causes of cases ( i.e. , why a specific individual is involved in a collision ) are different from the causes of population incidence ( i.e. , why there are over 3 million collisions per year in the united states ) .\nbuilding from the prevention paradox , the primary concept of rose 's strategy is that the majority of cases do not occur in individuals at high risk .\nthus , a large number of people exposed to a small risk may generate many more cases than a small number exposed to a high risk ( p.59 ) .\nthe recent study by beck provides an example of this principle related to road traffic fatalities . \nshow that pedestrians ( 13.7 deaths per 100,000 person trips ) , cyclists ( 21.0 deaths per 100,000 person trips ) , and motorcyclists ( 536.6 deaths per 100,000 person trips ) are at higher risk of a fatal collision than motor vehicle users . despite their higher risk ,\npedestrians , cyclists , and motorcyclists represent only 20.5% of those killed in traffic collisions . \nfigure 1 shows that in the usa the majority of trips ( 86% ) and therefore exposure to causes of collisions are greater for motor vehicle users .\nthus , the majority of those killed ( 76.6% ) are motor vehicle users who are , on average , at a lower risk ( 9.2 deaths per 100,000 person trips ) than other road users except public transit users .\nfor interventions to be effective in reducing the total number of road deaths and injury , they must target fundamental causes ( i.e. , causes of incidence ) , which would result in a global reduction in exposure to a fundamental cause for the entire population . according to the strategy of preventive medicine road traffic fatalities can be neither understood nor properly controlled if high - risk road users are thought to constitute the entire problem .\npolicies and practices that attempt to prevent traffic fatalities must consider all modes of transportation because they all contribute to the total number of deaths ( figure 1 ) [ 14 , 15 ] . in transportation research , the volume and speed of motor vehicle traffic could be considered two of the fundamental causes of collisions , for all road users [ 16 , 17 ] . throughout the paper , we consider exposure to moving vehicles as a fundamental cause of road traffic deaths and injuries . in this example\n, a global reduction in the amount of kilometers driven would result in a reduction of the likelihood of collisions for all road users , a left shift in the risk of road death and injury ( figure 2 ) [ 18 , 19 ] .\nfor all road users , including pedestrians and cyclists , a reduction in traffic volume contributes to a lower risk of injury and death .\nsignificant public health benefits could be achieved through macrolevel interventions that influence the level of exposure to traffic volumes for all road users , for example , land use and transportation policies that encourage using safer transportation modes ( e.g. , public transit ) and area - wide traffic calming schemes covering whole metropolitan areas , among others . in the usa ,\nrecent reductions of traffic volume were associated with a reduction in the total number of road fatalities .\nrose 's perspective is one way to critically appraise the challenge of reducing the overall burden of collisions while maintaining the benefits of effective mobility .\nthe implementation of interventions supported by rose 's strategy requires a dialogue between researchers , planners , policy makers , and the public . throughout this discussion\nwe must recall that the primary function of roadways is not to cause collisions but rather the mobility and productivity of the population . because roadways have multiple functions , policy makers , planners , health officials , and the public\nmay disagree on how to balance road safety with other competing functions . as rose states ,\n if a problem is common and has been around for a long time , then people come to accept it even if it is large : it is the exceptional or new which causes alarm .\nthe toll of deaths from road traffic accidents vastly exceeds that from crashing aero planes , but only the latter lead to public health inquiries ( p.57 ) .\nas the previous quote suggests , researchers must critically appraise their work and dialogue with policy makers and the public about complex transportation challenges in order to achieve an acceptable balance between the need for mobility and its consequences [ 2224 ] .\nideally , interventions will both improve mobility and reduce the public health burden of road traffic injuries .\nin particular researchers must be conscious of the potential influence of structural global economic forces lead by major car and oil companies in influencing road collisions research and discourse [ 21 , 2527 ] .\nbeck et al . state , our findings suggest that a shift from passenger vehicle travel ( lower risk ) to nonmotorized travel ( higher risk ) could result in an overall increase in the numbers of people killed in traffic \nmeasures that prevent crashes and injuries for pedestrians and bicyclists are needed , especially given the recent focus on increasing physical activity through active travel ( p.216 ) .\nsuggests that the high - risk approach is a more acceptable intervention than a population approach , which would reduce exposure to fundamental causes , volume of motor vehicles in our example , for all road users .\nhowever , in general , interventions targeting high - risk groups ( e.g. , walkers and cyclists ) have limited population wide benefit for injury prevention . targeting the causes of incidence to reduce exposure to motor vehicle volume for all road users , the population approach ,\nhas the potential for a greater reduction in the total number of transportation fatalities in a population than the high - risk approach . \ncompares a population approach and a high - risk approach targeting pedestrians and cyclists . in the usa , between 1999 and 2003 , a 25% reduction in the number of pedestrian and cyclist fatalities would have resulted in 1386 fewer deaths ( 1212 for pedestrians , 174 for cyclists ) . a greater number of lives would have been saved by a 4% reduction in the fatal risk for all road users ( table 1 ) .\ntable 1 estimates the hypothesized effect of decreasing fatal risk over the entire population of road users .\nit shows that a 10% and 15% reduction in the fatality risk for all road users would result in a reduction of 4213 and 6320 cases , respectively .\nthese scenarios would benefit motor vehicle occupants but also pedestrians and cyclists . in urban settings ,\na risk reduction of 15% could be achieved through area - wide traffic calming interventions . reducing the risk of road death and injury by intervening to reduce the level of exposure to traffic volumes , or other fundamental causes ,\nfirst , the potential reduction in road injuries and deaths is much larger than with high - risk approaches .\nsecond , a population - wide prevention strategy is of benefit to high - risk road users , whatever the criteria used to define high risk ( e.g. , transportation mode , alcohol consumption , age group ) .\nthird , it may also reduce other externalities including pollution , noise , physical inactivity of fundamental causes such as traffic volume [ 21 , 29 ] . for decades ,\nthe strong relationship between traffic volume and road traffic injuries or death has been reported , at the street , city , region , or country levels [ 30 , 31 ] .\nfor all intersections from a road network , safety performance functions show that the expected number of collisions at intersections increases as traffic volume increases , though this relationship is not linear ( figure 3 ) .\nthe traditional intervention strategy , recommended by the us department of transportation is to return deviant intersections to within an acceptable range of the average collisions rate at comparable intersections . as seen in figure 3(a ) , this targeted intervention approach aims to move the deviant intersections closer to the best fit regression line .\nthis is an example of a high - risk approach that does not address the entire population of intersections or injured individuals . in montreal , for example , only 4% of pedestrian injuries occurred at 22 identified black spot intersections , whereas the remaining 96% of pedestrians were injured at more than 3500 different crash sites , none of which were black spots .\nthe population strategy acknowledges that interventions should address the fundamental causes of road deaths and injuries , in our example , the level of exposure to moving vehicles over the entire population , and for all intersections .\nthe population approach would ask whether it was possible to globally reduce the exposure to traffic volume ( figure 3(b ) ) and subsequently reduce the risk of death and injury at any given intersection for all road users . as the arrows show in figure 3(b ) , the traffic volume and subsequent risk are reduced at every intersection . in theory , it would result in a greater reduction of the number of injured road users than targeting deviant streets and intersections .\nrather we present a promising approach to think about road traffic fatalities . a detailed reading of rose 's work [ 9 , 10 ] will provide more precision and help clarify interested readers understanding .\nit should be noted that rose 's ideas are not without considerable debate in public health [ 3335 ] .\nfor example , modeling studies suggest that rose 's approach is generally more cost effective ; however , in certain cases a high risk approach can have better cost / benefit ratios .\nfor example , recent studies suggest that when compared with other roads , streets with cycle tracks have a lower risk of injury for cyclists [ 36 , 37 ] .\nas well , the potential of rose 's strategy for reducing social inequities in health in general [ 34 , 35 ] and in particular road fatalities for those residing in low income areas is still debated .\na vulnerable population approach may be the most acceptable when attempting to act on social inequities ; however , a recent study has shown that reducing traffic volume at all intersections of a canadian city would be most beneficial in poorer neighborhoods .\ntransportation planning and public health have important historical roots . to address common challenges , including road traffic fatalities , integration of theories and methods from both disciplines is required .\ngeoffrey rose 's strategy of preventive medicine made an important theoretical contribution to public health and has applications to transportation .\nthis paper allowed for both public health and transportation research to critically appraise their practice and engage in informed dialogue with the objective of improving mobility and productivity while simultaneously reducing the public health burden of road deaths and injuries .", "answer": "transportation planning and public health have important historical roots . to address common challenges , including road traffic fatalities , integration of theories and methods from both disciplines is required . \n this paper presents an overview of geoffrey rose 's strategy of preventive medicine applied to road traffic fatalities . \n one of the basic principles of rose 's strategy is that a large number of people exposed to a small risk can generate more cases than a small number exposed to a high risk . \n thus , interventions should address the large number of people exposed to the fundamental causes of diseases . \n exposure to moving vehicles could be considered a fundamental cause of road traffic deaths and injuries . \n a global reduction in the amount of kilometers driven would result in a reduction of the likelihood of collisions for all road users . \n public health and transportation research must critically appraise their practice and engage in informed dialogue with the objective of improving mobility and productivity while simultaneously reducing the public health burden of road deaths and injuries .", "id": 44} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA local mode picture for H atom reaction with vibrationally excited H2O: a full dimensional state-to-state quantum dynamics investigation\n\nPaper sections:\n\nMolecular vibrations have profound effects on chemical reactivity. Consequently, it has been one of the central topics for chemical reaction dynamics to study how initial vibrational excitation in\ue104uences reaction dynamics. Early studies on atomdiatom reactions led to the establishment of the well-known Polanyi rules, which state that vibrational energy is more efficient in promoting a late-barrier reaction than translational energy, whereas the reverse is true for an early barrier reaction. 1 In past decades, substantial efforts have been devoted to understanding the dependence of reactivity on the initial excitation of a reactant mode for reactions involving polyatomic reactants. [2][3][4][5][6][7][8][9] The H + H 2 O / H 2 + OH reaction is the simplest system with different vibrational modes, and therefore has become a prototypical system for such a purpose. Crim, Zare, and co-workers carried out a series of experimental studies on the H + H 2 O/HOD/D 2 O reaction and its isotopically substituted analogies. Strong mode speci\ue103c reactivity has been observed in the H + H 2 O/D 2 O reactions with H 2 O/D 2 O in overtone or fundamental vibrational excitations, and bond selectivity has also been demonstrated in the H + HOD reaction with a preferential cleavage of the HOD vibrationally excited bond. [10][11][12][13][14][15] Theoretically, besides the quasiclassical trajectory (QCT) studies of Schatz et al., [16][17][18] there have been a number of quantum dynamics studies, [19][20][21][22][23] which are in qualitative agreement with the experimental observations. Recently, Fu et al. calculated the exact coupled-channel (CC) integral cross sections (ICSs) for H 2 O and HOD initially in the \ue103rst and second stretching excited states and simultaneous excitations of both bending and stretching modes on the YZCL2 PES, and observed strong mode speci\ue103c and bond selected reactivity as discovered in the experiments. 24,25 Another important question of mode speci\ue103city is how the initial vibrational excitation in\ue104uences the product state distribution. The Crim group observed that the reaction of water molecules excited to the |04i \u00c0 overtone state predominantly produces OH (v \u00bc 0), while the reaction from the |13i \u00c0 state produces mostly OH (v \u00bc 1). 12 The Zare group showed that for the D 2 O antisymmetric stretch fundamental states (001) and (011), the OD product is produced with little vibrational excitation In this letter, we report the \ue103rst full-dimensional quantum differential cross-sections (DCSs) for the title reaction with initial nonrotating H 2 O in the (000), (100) and (001) vibrational states to investigate the initial vibrational excitation in\ue104uences on the product state distribution and DCS. The H + H 2 O 4 H 2 + OH and its isotopically substituted reactions are the prototype for the theoretical study of tetra-atomic reactions, in much the same way that the H + H 2 reaction served as the prototype for triatomics. Because three of the four atoms are hydrogens, the system is an ideal candidate for high quality ab initio calculations of a potential energy surface (PES), as well as for accurate quantum reactive scattering calculations. In the past few years, a number of PESs have been constructed with an increasing level of accuracy, [26][27][28][29][30] making the system the \ue103rst four-atom reaction with a quantitatively accurate PES. Through the development of the time-dependent wave-packet (TDWP) method, \ue103ve-dimensional (5D) state-to-state DCSs were calculated for the H + H 2 O / H 2 + OH reaction with the nonreactive OH bond length being \ue103xed for the initial ground rovibrational state. 31,32 Recently, the full-dimensional state-to-state DCSs were reported for the HD + OH / H 2 O + D and D 2 + OH / HOD + D reactions with unprecedented agreement with experiments, 29,33,34 declaring that theory is now able to compete with experimentation in studying simple four-atom reactions at the state-to-state level on given accurate PESs.
We employed the CXZ PES in our calculations, 30 which is the most accurate and smooth PES available, constructed by the neural network (NN) method [35][36][37] based on 17 000 ab initio points calculated at the UCCSD(T)-F12/AVTZ level of theory. The full-dimensional state-to-state quantum calculation is carried out by using the improved reactant-product-decoupling (RPD) scheme based TDWP method. 38,33 The numerical parameters used in the reactant atom-triatom coordinates are as follows: the interaction region was de\ue103ned by a rectangular box of [1.0,6.0]a 0 in the r 1 coordinate, and [1.0,6.0]a 0 for the R coordinate. The number of vibrational basis functions used was 40 for the r 1 coordinate. For the R coordinate, we used 40 sine discrete variable representation (DVR) points. The asymptotic region was de\ue103ned from 6.0 to 12.0 a 0 with 42 sine DVR points for the R coordinate and 8 vibrational basis functions for the r 1 coordinates. The number of vibrational basis functions for the nonreactive OH is 12 for interactions and 7 for asymptotic regions. For the rotational motion, we used j 1max \u00bc 28 and j 2max \u00bc 50, and up to 9 K blocks to compute state-to-state reaction probabilities for J up to 40 to get converged DCSs. Continuous propagation in the product diatom-diatom coordinates only involves a total number of 120 sine functions for the translational coordinate R 0 in a range of [3.0,15.0]a 0 , 5 vibrational basis functions for the H 2 bond, and 3 vibrational basis functions for the OH bond. We used j 1max \u00bc 30 and j 2max \u00bc 18, and up to 11 K blocks for J \u00bc 40. To minimize the computational cost, the coordinate transformation is carried out at every 8 propagation time steps. Since one OH bond is treated as a nonreactive bond in this work, the reaction probabilities and cross sections should be doubled.
Fig. 1 shows the DCSs for the three initial states, each at four collision energies from the threshold energy, in terms of surface plots for the product translational energy and angle distributions for the reaction. It can be seen at the \ue103rst glance that the \ue103rst symmetric (100) and antisymmetric (001) stretching excited states have essentially identical DCSs. Just like the ground initial state, the DCSs for these two states are strongly backward peaked at the threshold energy. As the collision energy increases, the angular distribution becomes increasingly broader, and the peak position starts to shi\ue09d gradually to a smaller angle, consistent with the fact that the title reaction is a direct reaction via an abstraction mechanism. At the same collision energy, the DCS for the ground state is very different Fig. 1 Surface plots for the product translational energy and angle distributions for the three initial states (000), (100) and (001) at several collision energies.
from those for the vibrationally excited state. However, one may note that the DCSs at each column shown in Fig. 1 resemble each other very well, indicating that the angular distributions for these three states are similar at the same total energy (because the excitation energy for (100) and ( 001) states are about 0.454 and 0.466 eV, close to the collision energy difference between the ground and vibrationally excited state shown in the \ue103gure).
In order to examine the effect of the stretching excitation on the angular distribution in a quantitative manner, we present the total DCSs for the three states at collision energies of 0.8 eV, 1.0 eV, and 1.2 eV in Fig. 2(a). As seen, the vibrational excitations dramatically enhance the DCSs, but with the enhancement factor decreasing considerably as the collision energy increases. The behavior of angle distributions for the excited states is quite different from the ground state at the same collision energy, and the former are sideways peaked and have obvious forward scattering components at E c \u00bc 1.2 eV. Moreover, the DCSs for the (100) state are only slightly larger than those for the (001) state at large scattering angles, indicating that one quantum in the symmetric or antisymmetric stretching excitation of H 2 O has nearly identical effects to DCS. Fig. 2(b) shows the total DCSs for the three states at total energies of 0.8 eV, 1.1 eV, and 1.4 eV, which are measured with respect to the energy of the H 2 O ground rovibrational state. Overall, the angle distributions for (000), ( 100) and (001) vibrational states are quite similar at the same total energy of reaction, although the excited states increase the cross section by at least 10 times relative to that for the ground state. As the total energy increases, the sideways scattering components increase substantially, and gradually become dominant. At E tot \u00bc 1.4 eV, the angular distributions for the excited states are slightly broader with peaks at 103 , than that for the ground state with a peak at 113 . Therefore, the energy initially deposited in stretching vibrations is much more efficient than the translational energy at promoting the reaction, but has rather similar effects on product angular distribution as the translational energy.
Fig. 3 shows the product H 2 (v \u00bc 1) and OH (v \u00bc 1) vibrational state populations for the three initial states as a function of total energy. It should be noted that the population for (000) state in Fig. 3(b) was multiplied by a factor of 5 before plotting. When H 2 O is in the vibrational ground state, both H 2 and OH products are vibrationally very cold in the energy region considered here. There is a small fraction of H 2 (v \u00bc 1) produced only for a collision energy higher than 1.25 eV with a population of 1.1% at 1.5 eV, and almost no OH (v \u00bc 1) produced. The initial vibrational excitations increase the branching ratios of H 2 (v \u00bc 1) and OH (v \u00bc 1) channels at the same total energy. The population of H 2 (v \u00bc 1) reaches 7.7% at E tot \u00bc 1.65 eV. However, the OH vibration excited populations remain small for the initial (100) and (001) states.
These small populations of OH (v \u00bc 1) clearly reveal that H 2 O fundamental stretching excitations produce vibrationally \"cold\" OH as the ground initial state, in agreement with the experimental observation of Zare and coworkers. 15 In the normal mode picture, the (100) and (001) state correspond, respectively, to the symmetric and antisymmetric vibrational excitations of H 2 O with both OH bonds vibrationally excited. Breaking one OH bond by an incoming H atom will leave another OH bond vibrationally hot. However, in the local mode picture, the (100) and (001) states correspond to |10i AE \u00bc 2 \u00c01/2 (|10i AE |01i), i.e. each OH bond is a superposition of the ground and \ue103rst excited quantum states. When the incident H comes in, it will react with each quantum state independently without any effect from the non-reacting OH group if the non-reacting OH is a spectator, producing OH in the corresponding quantum state. Because the reactivity of the OH excited state is much higher than the ground state, the incident H atom tends to react with the excited state, producing OH mainly in the corresponding ground state. On the other hand, the H atom also reacts with the ground OH state, producing a small fraction of the OH (v \u00bc 1) state. The fraction of OH (v \u00bc 1) should be approximately equal to the relative reactivity between the OH (v \u00bc 0) and OH (v \u00bc 1) states. As can be seen from Fig. 3(b), the fraction of the OH (v \u00bc 1) population is very close to the relative reactivity. Therefore, the local mode picture works very well here, and the non-reacting OH bond does act as a spectator.
Fig. 4 shows the fraction of total available energy in the product channel going into the rotation and vibration excitation of H 2 and OH as a function of total energy. For the ground state reaction, less than 25% of the available energy goes into the rotational motion of the products in the energy region considered here, and only a very small fraction appears as vibrational energy. The H 2 rotation excitation carries away an increasingly large portion of the internal energy with the increase of collision energy, while the fraction of energy going into the OH rotation excitation essentially does not change with the collision energy. For the excited states reaction, the product rotational distributions are close to those for (000) at the same total energy, leading to a small difference in the fraction of energy. For the H 2 vibration, the difference is bigger. The fraction obtained from vibrationally excited H 2 O is about a factor of 3.5 larger than that from the ground state H 2 O at E tot \u00bc 1.5 eV.
Therefore, our state-to-state quantum dynamics study revealed that the stretching excitation is much more efficient at promoting the reactivity than the translational energy, but has a rather similar effect on the angular distribution as the translational energy. The small populations of OH (v \u00bc 1) from ( 100) and (001) initial states can be explained clearly by the local mode picture of H 2 O vibration, and reveals that the non-reacting OH does act as a spectator in the reaction. More theoretical efforts should be put into studying higher levels of vibrational excitation and other X + H 2 O reactions in the future to further deepen our understanding of mode-speci\ue103c chemistry.
", "answer": "A local mode picture was postulated some time ago to explain the negligible OD product excitation from H reacting with D 2 O in fundamental asymmetrical excitation: the D 2 O asymmetric stretch state is best thought as a linear combination of local mode stretches with the H atom reacting preferentially with the excited OD bond, but has never been verified. Here we report the first full-dimensional state-to-state study for the title reaction with H 2 O in the ground and the first symmetric and asymmetric stretching excited states. It is found that symmetric and asymmetric stretching excited states, which vibrate in very different ways in the normal mode picture, behave essentially identically in the reaction. More importantly, our calculations revealed that the reaction produces a small fraction of OH in the v \u00bc 1 state, with the population close to the relative reactivity between the ground and vibrationally excited states, and therefore it confirms the local mode picture for H 2 O in symmetric or asymmetric stretch states when reacting with an H atom.", "id": 45} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe aim of vital pulp therapy ( vpt ) is to use biomaterials in order to safeguard as much vitality as possible for the dental pulp with carious exposure . direct pulp capping and pulpotomy , the two main vpt procedures , are less invasive than pulpectomy / root canal therapy ( rct ) .\nit is well known that the most common cause of pulp / periapical diseases is the presence of bacteria and their by - products within the involved tooth , and the most common pathway of their entrance is through carious lesions ; when further bacterial recontamination is prevented with a good biological seal , the exposed dental pulp has the capability to heal and construct a new dentinal bridge and periapical tissues have the ability of regeneration .\nthere is a body of evidence for biocompatibility and sealing ability of mineral trioxide aggregate ( mta ) .\ncurrently , mta is as an alternative gold standard for calcium hydroxide , a traditional gold standard , in the field of vpt .\nthis biomaterial creates a biological seal via hydroxyapatite crystal formation which is improved the first physical seal . despite the advantages , mta has nonpredictable antimicrobial activity , delayed setting time , poor handling characteristics , as well as high cost . the calcium - enriched mixture\n( cem ) cement is a newly introduced endodontic biomaterial with similar clinical applications as mta , but different chemical compositions .\nthis novel cement has an antibacterial effect comparable to calcium hydroxide and superior to mta and sealing ability similar to mta .\nrecent researches revealed that the biologic response of the pulpal and periapical tissues to the mta and cem cement were comparable in dogs teeth .\nhydroxyapatite crystal formation was reported over the set cem even in normal saline solution . besides the surface characteristics of the set cem cement , as well as the distribution pattern of calcium , phosphorus , and oxygen ions , is similar to dentine .\nlast but not least , the clinical use of cem has been approved by the iranian ministry of health and medical education . even after carious pulp exposure of symptomatic permanent molars , the pulp can heal , as it has been shown in several studies using mta and cem cement as pulp - capping biomaterials .\nthis case report discusses a successful treatment outcome of pulpotomy treatment in a symptomatic mature molar with established irreversible pulpitis associate with condensing apical periodontitis .\ndiagnostic tests were performed ; the involved tooth responded with mild pain to percussion and severe lingering pain to the cold thermal test .\nit was not responded within normal limits to the electric pulp test ( ept ) .\na radiographic examination showed a large carious lesion associated with condensing apical periodontitis [ figure 1a ] .\n( a ) preoperative radiograph shows a large carious lesion associated with a condensing apical periodontitis .\n( b d ) six months , 1 year and 2 years follow - up radiographs , respectively ; a complete resolution of condensing apical periodontitis is evident .\nnote the existence of a dentinal bridge beneath the cem cement ; the remaining pulp canal space does not obliterated following clinical and radiographic diagnostic examination , pulpotomy of the first mandibular molar was decided as the treatment .\nthe tooth was anesthetized with 2% lidocaine with 1:80,000 epinephrine ( daroupakhsh , tehran , iran ) , isolated with a rubber damn and then caries was excavated ; the exposed coronal pulp tissue was removed with a sterile round diamond bur with water spray .\nhemorrhage was controlled with sterile cotton pellets ; a ~2 mm layer of the cem cement ( bioniquedent , tehran , iran ) was placed without any pressure to cover the exposed pulp stump .\nthe patient was re - examined clinically after 1 and 7 days ; tooth mobility was within the normal physiological range , the percussion test was slight positive to negative , and patients were asymptomatic .\nsix months , one - year , and 2-years follow - ups revealed no clinical or radiographic pathological findings ( i.e. inflammation , infection , calcification , and resorption ) on the first mandibular molar ; radiographs showed normal periodontium apparatus , an evidence of complete periapical healing [ figure 1b d ] .\nthe root canal treatment of teeth with irreversible inflamed pulps is basically a prophylactic treatment , since the radicular vital pulp is frequently free of infection and the rationale is to avoid further infection of the root canal system . improved and more conservative vpt has the potential to reduce the need for more invasive / complicated rct .\nhowever , if this is to be achieved in permanent teeth , there is a need for suitable biomaterials for vpt , particularly pulpotomy . in this report , a case of established irreversible pulpitis associated with condensing apical periodontitis\nrecall examinations revealed that treatment outcomes were successful in preserving pulpal vitality and complete periapical healing of the tooth .\nit has been suggested that the existence of a dentinal bridge may at least be an indicator of vpt success , and there are several studies that point to its clinical importance .\nhowever , researchers reported the presence of tunnel defects in dentinal bridge under calcium hydroxide in vpt.[52122 ] they concluded that tunnel defects can serve as pathways for bacterial leakage . unlike ch , the calcified bridge formed by mta is continuous and has no evidence of tunnel defects . according to histological evidence from animal / human studies in mature permanent teeth , the cem cement , like mta , saves pulp vitality and also induces a hard tissue bridge formation , the both .\ndentine bridge induced by the cem cement has been shown to be similar to that induced by mta in terms of thickness , absence of tunnel defects , presence of adjacent odontoblast - like cells , predentine , and dentinal tubules .\nan important finding was the complete healing of the condensing apical periodontitis with reconstruction of bone structures to normal appearance surrounding the involved molar .\nmild inflammatory processes may at times cause the formation of condensing apical periodontitis , mostly involving the mandibular first molar .\nvarious studies have suggested that the key factor in success of vpt is the sealing ability of the material ; on the other hand , the most important cause of failure is bacterial recontamination .\nthe cem cement favourably prevents microleakage and has sealing ability comparable to mta and superior to irm .\nin addition , the cem cement was an effective antibacterial agent . therefore , when bacterial contamination is removed from the dentin - pulp complex in addition to a creation of tight coronal seal to prevent further bacterial recontamination the inflamed but vital pulp of a permanent molar has a chance to return to a healthy and functional status .\nall these are resulted in removing the etiologic factor of periapical lesion and complete periapical healing . because pulp / periapical healing was achieved without any need for further intervention\n, it seems that the cem cement has the required and acceptable properties to be used as a pulp protective biomaterial .\nthe exact biological mechanism by which the cem cement promotes pulp healing is currently unknown .\nthis characteristic is likely to be the result of several properties such as sealing ability , high alkalinity , antibacterial effect , biocompatibility , i.e. dentinogenesis , cementogenesis , low cytotoxicity , pain relief effect , anti - ierr ( inflammatory external root resorption ) effect , hydroxyapatite formation , and similarity to dentine .\nbesides , recent interesting studies have established favourable treatment outcomes for the cem cement when used in pulpotomy of human permanent teeth with irreversible pulpitis . in the future , biomaterials can play an important role in regenerative dentistry ; they may completely transform our whole philosophy of endodontic treatment .\nendodontics seems to be on the brink of an era when a diseased pulp can be a saved one .\nthere is a realistic biological argument to perform pulpotomy as a promising alternative endodontic treatment in mature permanent teeth ; the results of this case clearly show that cem cement can be used clinically in the treatment of a mature molar associated with irreversible pulpitis and condensing apical periodontitis .", "answer": "this case report describes a pulpotomy treatment of a permanent mature molar tooth with established irreversible pulpitis and condensing apical periodontitis , using calcium - enriched mixture ( cem ) cement . \n clinical examination revealed that the first right lower molar had a large carious lesion with history of spontaneous / lingering pain ; radiographic examination showed condensing apical periodontitis . \n pulpotomy was opted as the treatment ; cervical pulpotomy was carried out . \n following hemostasis , the radicular pulp stumps were covered with ~2-mm - thick layer of the prepared cem cement ; the tooth was restored with amalgam . \n two - year follow - up showed that the treated tooth had been symptomless , and there were no clinical signs / symptoms of either inflammation or infection . \n radiographically , the periradicular lesion was completely healed with reconstruction of bone structures to normal appearance ; the root canals were not calcified . according to chemical , physical , and biological properties of the cem cement , \n this novel biomaterial may be suitable for endodontic treatment .", "id": 46} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit was recently suggested that endometriosis may commence as an endometrial disease provoked by the aberrant expression of aromatase in this tissue , as this appears to play a pivotal role in its survival in ectopic locations.4 gene array studies have shown that the expression profiles of endometriosis lesions and the eutopic endometrium are similar , which supports the hypothesis that endometriosis is an endometrial disease.6 it is biologically plausible that the presence of aromatase activity in the endometrium is pivotal for the development of endometriosis by blocking phagocytosis by activated macrophages and may also be responsible for the exacerbation of menstrual symptoms whose onset predates the diagnosis of this pathology.1,4,7 in this hypothesis , endometriosis would be a late consequence of enzymatic changes that occur in the endometrium prior to its establishment outside the uterus , which could explain the lag that is often reported between the onset of symptoms and diagnosis of the disease .\nthis hypothesis could be tested by examining patients with severe dysmenorrhea or infertility to determine whether laparoscopy reveals endometriosis despite aromatase expression already being positive in the endometrium . in the present study\n, aromatase expression was determined in the eutopic endometrium of patients with severe menstrual symptoms and/or infertility who underwent laparoscopy and hysteroscopy as a part of their diagnostic work - up .\na total of 106 patients of reproductive age ( range = 1847 years ) received a laparoscopy and hysteroscopy with endometrial biopsy that was carried out using a 4 mm karman curette attached to a 10 ml syringe to produce a vacuum , which is the standard procedure for the evaluation of menorrhagia , severe dysmenorrhea , or infertility in the day hospital where the current study was carried out .\nall patients included in this group had reported at least two of these three symptoms for periods ranging from 2 to 8 years .\nthe control group consisted of sixteen patients who received a laparoscopy for reasons unrelated to infertility or severe dysmenorrhea and who were found to be endometriosis - free during the examination .\nthe indications for laparoscopy in this group were either benign non - endometriotic ovarian cysts ( seven patients ) or tubal ligation ( nine patients ) . in these patients ,\nan endometrial biopsy was performed at the time of the laparoscopy using a 4 mm karman curette .\nthe patients enrolled in the study gave written informed consent for immunohistochemical studies to be carried out on the endometrial biopsy specimens obtained as part of their standard medical care .\nlaparoscopies were performed either during the proliferative phase ( n = 72 ) or in the secretory or menstrual phase ( n = 34 ) , since the timing of the procedure depended on the availability of the surgical theater and the specifics of the institution s waiting list .\nthe laparoscopy reports and color images were retained in the patients files for further evaluation if necessary . during the laparoscopy procedure ,\nthe surgical team ascertained the presence of endometriosis and graded the stage of the disease in accordance with the american society of reproductive medicine ( asrm ) classification .\n8 using laparoscopic classification criteria , the patients with endometriosis were divided into four groups according to the severity of their lesions , using the asrm classification of minimal ( stage i ) , mild ( stage ii ) , moderate ( stage iii ) , or severe ( stage iv ) .\nthe severity of menstrual symptoms such as dysmenorrhea , the presence or absence of infertility , and the reason for laparoscopy were recorded in the patients files .\naromatase expression was investigated using the commercially available monoclonal antibody mca2077 clone h4 ( serotech , raleigh , nc ) .\nantigen retrieval was performed using tris - edta buffer ( ph 8.0 ; sigma - aldrich , so paulo , brazil ) .\nthe presence of aromatase expression was rated as positive if there was any detectable staining reaction in the glandular epithelium or negative when no reaction was observed .\nplacental tissue and an atrophic endometrial sample were used as positive and negative controls , respectively , in all immunostaining reactions for aromatase p450 .\nstatistical analysis was performed using the one - tailed chi - square test for differences in percentages , using an unnamed online interactive calculation tool for chi - square tests of goodness of fit and independence , which is hosted at http://quantpsy.org .\nin the group of patients with severe dysmenorrhea , endometriosis was diagnosed in 90/106 patients . in the remaining 16 cases ,\naromatase expression in the eutopic endometrium was detected by immunohistochemistry mainly in the glandular epithelium ( figure 1 ) .\nthe staining reaction was positive in 66/92 patients ( 72% ) with endometriosis and symptoms of dysmenorrhea and/or infertility , and there were no significant differences between the phases of the patient s menstrual cycle . in symptomatic patients who were found to have normal pelvic results during the laparoscopy ,\naromatase expression was still positive in the endometrium in 13/14 cases ( 95% ) , though this difference was not statistically significant ( p = 0.09 ) . in the asymptomatic control group without endometriosis , however , aromatase expression was negative in the eutopic endometrium in all cases . in the subset of symptomatic patients with a laparoscopic diagnosis of endometriosis ,\nthe percentage of endometrial samples positively expressing aromatase in the glandular epithelium showed a trend toward greater positivity as the severity of the disease increased in accordance with the asrm criteria .\naromatase expression was detected in the eutopic endometrium of 28/45 patients with stage i endometriosis ( 62% ) , 11/14 patients with stage ii ( 78% ) , 14/20 patients with stage iii ( 70% ) and 12/13 patients with stage iv endometriosis ( 92% ) .\nhowever , only the difference between stages i and iv of the disease was statistically significant ( p = 0.04 ) ( table 1 ) .\nthe present study not only showed an association between the presence of aromatase expression in the eutopic endometrium and the severity of endometriosis lesions at laparoscopy but also suggests that this expression was already present in symptomatic patients in whom pelvic endometriosis was not found .\nthese findings agree with the hypothesis that endometriosis may commence as an endometrial disease resulting from functional changes in the endometrium before the disease establishes outside the uterus .\nthe presence of similar epigenetic changes in the eutopic endometrium and the endometriotic lesions further corroborates the hypothesis that endometriosis is an endometrial disease.6 the positive correlation between mrna levels in the eutopic endometrium and the severity of endometriosis and adenomyosis also supports this hypothesis .\n9 whether endometriosis starts as an endometrial disease before establishing itself elsewhere in the pelvis6,7 can not be proven by the present study , but previous work shows that the onset of symptoms associated with this pathology may commence many years prior to its diagnosis , which support this hypothesis .\n1 the occurrence of severe dysmenorrhea for many years prior to a diagnosis of endometriosis may reflect these initial endometrial changes favoring the upregulation of both estradiol and prostaglandin production in this tissue.4,6,7 the occurrence of such symptoms in patients with a normal pelvis at laparoscopy , as shown in the present study , may suggest that these functional changes in the endometrium are not only associated with the onset of endometriosis - related symptoms but that they may occur prior to the diagnosis of any pelvic pathology by laparoscopy .\nfunctional endometrial changes leading to an increase in aromatase expression may therefore predate the development of endometriosis , initially provoking dysmenorrhea and possibly infertility before triggering the development of the disease outside the uterus.4 it still remains to be determined whether this group of symptomatic patients represents a high - risk population for the development of endometriosis . in patients with an established diagnosis of endometriosis , however , endometrial positivity for aromatase tends to increase with the severity of the disease .\nthis may be due to the greater possibility of spontaneous regression of early stage endometriosis , which may occur because of reduced aromatase activity in the eutopic endometrium .\nalthough aromatase expression in the eutopic endometrium may be pivotal for the onset and progression of endometriosis , it has yet to be clarified how this enzyme affects the development of endometriosis .\nthe role played by estrogens in inhibiting immune surveillance by activated macrophages has been suggested as one of the likely mechanisms by which aromatase affects the course of endometriosis.4,7,10 this local estrogen production in the endometrial cells shed to the pelvis in retrograde menstruation may favor their survival in these ectopic locations by directly preventing their destruction by activated immune cells through the inhibition of the phagocytosis mechanism.1013 the presence of aromatase in the eutopic endometrium may therefore represent the initial step in the development of endometriosis and could be necessary for the development of lesions outside the uterus.7 the similar genetic alterations found between endometriotic lesions and the respective eutopic endometrium also indicate a common histological origin.7 the current study s finding that aromatase expression is detectable by immunohistochemistry in the endometrium of symptomatic , endometriosis - free patients agrees with the hypothesis that this enzyme initially exacerbates dysmenorrhea or causes infertility prior to facilitating the development of endometriosis elsewhere in the pelvis .\na previous study has shown that aromatase expression in the endometrium reduces implantation rates in patients undergoing in vitro fertilization , however , which may help to explain the lower fertility rate of women with endometriosis.14 the presence of aromatase and other enzymes related to estrogen metabolism in the eutopic endometrium will ultimately create a hyperestrogenic milieu , resulting in increased prostaglandin production , particularly because cox-2 expression is upregulated by estradiol in this tissue.69,12,13 this would explain why the pelvis of a patient with severe dysmenorrhea or infertility may be normal , as was reported in the current study \naromatase expression in the eutopic endometrium may be sufficient to provoke these symptoms by enhancing the production of proinflammatory prostaglandins in this tissue .\nhowever , the possibility that some of these endometriosis - free patients have adenomyosis can not be completely excluded in this study , despite the fact that myometrial findings were normal at transvaginal sonography .\nestrogens produced locally in the endometriotic lesions and eutopic endometrium result in the mechanism of decreased immune surveillance and enhanced tolerance found in endometriosis,14 which may explain the inverse relationship between estrogen levels and impaired nk - cell function found as a function of the severity of the disease .\n15 local estrogen production would also stimulate the production of vegf , growth factors , and inflammatory cytokines by immune cells , thus favoring the progression of endometriosis.12,15,16 the blockade of phagocytosis by the local production of estrogens and the concomitant stimulation of growth and inflammatory factors would explain the paradoxical effects of macrophages in endometriosis , which seem to interact with rather than destroy these ectopic endometrial cells , thus enhancing their growth and angiogenesis.12,17 in conclusion , a vicious cycle of enhanced inflammation and local estrogen production mediated by cox-2 and aromatase expression in the eutopic endometrium of endometriosis patients may play a pivotal role not only in determining the clinical course of this disease but also in defining the intensity of its debilitating symptoms . in the pelvic cavity ,\nthe ensuing inflammatory reaction provoked by the arrival of endometrial cells will further exacerbate their preexisting aromatase activity , thus augmenting local estrogen production and halting phagocytosis by activated macrophages.6,7", "answer": "objectiveto investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy.patientsthe study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility . \n sixteen endometriosis - free asymptomatic patients were used as a control group.methodsconcomitant laparoscopy and hysteroscopy was carried out in all cases . \n an endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry . \n endometriosis was staged according to the american society of reproductive medicine classification.resultsendometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients . in this group , \n aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis ( 72% ) and in 13/14 ( 95% ) patients in the symptomatic , endometriosis - free group ( p = 0.09 ) . \n aromatase expression was not detected in any patients from the control group . in the endometriosis group , \n aromatase expression was detected in the eutopic endometrium of 28/45 patients ( 62% ) with american society of reproductive medicine classification stage 1 of the disease , in 11/14 patients ( 78% ) with stage ii , 14/20 patients ( 70% ) with stage iii , and in 12/13 patients ( 92% ) with stage iv ; however , the difference was only statistically significant between stages i and iv ( p = 0.04).conclusionaromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis . \n when endometriosis was present , however , there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity .", "id": 47} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nclassic bladder exstrophy ( be ) is a rare malformation of the genito - urinary tract affecting 1:50,000 - 1:100,000 live births .\nthe surgical reconstruction of the be - epispadias complex has evolved significantly during the last 50 years but is still challenging for the most experienced pediatric urologists , surgeons , and orthopedists .\nthe upper tracts are almost always normal in the neonates with classic be before abdominal wall , posterior urethral , and bladder closure . the upper tract changes or deterioration of renal function almost always occurs after reconstructive surgery .\nthe objectives of treatment are to achieve a secure closure of the bladder , pelvis , and the abdominal wall ; preservation of renal function ; urinary continence and creation of functional and cosmetically appealing genitalia .\ngrady and mitchell have described complete repair of classic be with the combination of bladder closure and epispadias repair at birth . however , the modern staged repair of exstrophy is still considered the gold standard .\nthis involves bladder closure shortly after birth , followed by epispadias repair at 6 - 12 months of age and bladder neck reconstruction at 4 - 5 years of age . to assess the success of staged reconstruction of the be and its effect on the upper urinary tract , we have analyzed the renal function and continence in 30\nbetween 1994 and 2013 , 30 patients with be have been managed at our institute in various stages of repair , 7 were females and 23 were male patients .\nof 30 patients 27 patients underwent primary repair and 3 patients were referred for secondary be closure .\ntwenty - one children presented before 1 year of age ; four neonates presented before 72 h of birth , in whom bladder closure was done without osteotomy with hip spica only .\nthree of these patients , who were operated without osteotomy , had bladder dehiscence , hence have undergone secondary repair with bilateral anterior iliac osteotomy and immobilization with external fixators ( efs ) .\neight patients presented before 3 months of age ; all underwent primary bladder closure with bilateral anterior iliac osteotomy and immobilization with hip spica .\nnine patients presented between 4 months and 1 year of age , all were operated with primary or secondary exstrophy repair with bilateral anterior iliac osteotomy and immobilization with efs .\ntwo of these children referred with bladder dehiscence , had primary repair with posterior iliac osteotomy ; hence , secondary exstrophy repair was carried out with bilateral anterior iliac osteotomy .\neight children presented between 1 and 5 years of age and one child presented at 9 years of age ; all underwent bladder closure with bilateral anterior iliac osteotomy and immobilization with efs .\nthe mean and median age of exstrophy repair was 1.25 years and 4 months , respectively .\none patient had failure and six had penopubic or urethro - cutaneous ( uc ) fistulae .\nthe average age at the time of epispadias repair was 5 years ( 212 years ) .\nthe triangular flaps of the bladder were incorporated into the bladder instead of de - epithelializing , and using these to buttress the bladder neck repair .\nthirteen children have undergone guy leadbetter bladder neck reconstruction , eleven males and two females .\neight children are continent for more than 2 h with good nocturnal continence ; one female child needs clean intermittent self - catheterization ( cisc ) every 34 h for bladder emptying .\ntwo other children also have undergone augmentation cystoplasty and are on cisc every 34 h. one male child , who underwent exstrophy reconstruction at 9 years of age , has surprisingly developed continence after epispadias repair only .\ninterestingly , one female child who presented at 3 years of age with good bladder plate was operated with bilateral cephalo - trigonal ureteric reimplantation , trigonal tubularization , and bladder and abdominal wall closure with bilateral anterior iliac osteotomy is continent for 3 h after single - stage repair only [ figures 1 and 2 ] .\nfemale exstrophy child with good bladder plate micturating cystourethogram showing good bladder capacity the average age at the time of bladder neck repair was 8 years ( 416 years ) and the mean bladder capacity at the time of repair was 100 ml ( 80200 ml ) .\nthirty patients have undergone primary or secondary bladder closure , four neonates presenting before 72 h of life were operated without osteotomy , three of these developed dehiscence .\nhence , following this all children were operated with bilateral anterior iliac osteotomy either with hip spica in infants <3 months and efs in all children older than 3 months [ table 1 ] .\nprimary bladder exstrophy repair / secondary bladder exstrophy repair eighteen children have undergone modified cantwell ransley epispadias repair , one had a failure and was successfully repaired again .\nsix children had uc fistula postoperatively ; three healed spontaneously and three required repair [ table 2 ] .\ncantwell - ransley epispadias repair thirteen patients have undergone all stages of be repair ; nine are continent for more than 2 h , and four children are continent for < 2 h. one child is continent after single - stage repair ; another child has developed continence after epispadias repair only .\none child with failed bladder neck repair and two children whose bladder capacity was < 80 ml have undergone augmentation cystoplasty .\nhence , out of 17 patients ; 14 are socially continent with good nocturnal continence .\ntwo children , who had undergone augmentation cystoplasty , have developed chronic renal failure and are on hemodialysis .\nthese changes resulted from progressive hydronephrosis due to bladder outlet obstruction after bladder closure in one female patient and after urinary diversion in another male child .\nfive patients developed bladder calculi after be or epispadias repair , and have developed renal scarring .\nthese patients who developed renal scarring following closure had one or more documented febrile urinary tract infections .\nfour patients who are coming for regular follow - up have still not developed adequate bladder capacity and are awaiting continence procedure [ table 3 ] .\nthe modern staged approach to be reconstruction has undergone significant changes since it was first advocated by jeffs and cendron as quoted by gearhart .\nhowever , the goal of upper tract preservation , obtaining urinary continence , and achievement of satisfactory functional and cosmetic external genitalia remains same .\nnonetheless , this success is associated with some risk to the upper urinary tract . usually , these complications are seen after failed initial closure , which can be categorized as complete dehiscence , bladder prolapse , and outlet obstruction . in our series ,\nthree neonates who were operated without osteotomy had bladder dehiscence ; other 27 children who were operated with bilateral anterior iliac osteotomy did not have bladder dehiscence .\nthe most critical support for osteotomy is that it allows tension free closure , which prevents subsequent dehiscence and organ prolapsed .\nstudies from europe and north america have shown that patients requiring repeat closure after failed attempt are less likely to have undergone osteotomy at initial closure .\nchildren operated before 3 months of age had primary bladder closure with bilateral anterior iliac osteotomy and immobilization with hip spica .\nin indian summers , it is difficult to maintain hygiene and avoid wound infection in hip spica .\nbhatnagar incorporates triangular flaps after urethral lengthening in the bladder repair ; we also incorporate these triangular flaps for the bladder repair .\nthis not only helps in utilizing bladder tissue for enhancing the bladder capacity but also improves the results of surgery with regard to urinary continence .\nthe patients with outlet obstruction after initial closure are at risk of hydronephrosis , severe reflux , pyelonephritis , and renal scarring .\none female child with outlet obstruction developed renal scarring and is on hemodialysis . in a review by baker et al .\nof exstrophy database , 29 boys and 12 girls were found to have posterior urethral obstruction after closure in the neonatal period . in our patients ,\nthe most common method of presentation was urinary tract infection seen in eight patients ; of these five had bladder calculi due to intersymphyseal stitch erosion into bladder and one presented with urinary retention .\nnow we prefer to use dexon suture for pubic symphyseal closure rather than prolene suture .\nhave revealed an acceptable risk of renal deterioration with 14.7% of patients developing renal deterioration over a follow - up of 12.7 years .\nthese authors suggest that most significant factors in the development of upper tract scarring after bladder closure are one or more febrile urinary tract infections , failure to use prophylactic antibiotics after bladder closure and presence of progressive hydronephrosis . in baker\net al . series , 22% had upper tract deterioration , including two with chronic renal insufficiency . in our series also , three patients ( 10% ) have developed renal deterioration .\nthe above statistics clearly suggest that in an infant or child with be , a febrile urinary infection should warrant a renal and bladder ultrasound to rule out hydronephrosis , hydroureter , and to assess bladder emptying . since all patients with exstrophy have various degree of reflux , all should receive chemoprophylaxis .\nthe prophylaxis should be continued until ureteric reimplantation and bladder neck reconstruction performed and reflux cured and appropriate bladder emptying proven on ultrasound .\nthe development of hydronephrosis after bladder neck repair can be due to ineffectual bladder emptying , a small inelastic bladder that is not capable of handling increasing volume of urine over time or ureteral obstruction secondary to reimplantation .\nthis can occur any time after repair , hence the importance of constant regular follow - up evaluations . in our series also , one child developed altered renal function due to small inelastic bladder not capable of handling the increasing volume of urine .\nalthough modified staged reconstruction is being performed at many institutes , grady and mitchell have proposed total reconstruction consisting of the bladder and urethral closure with penile disassembly in the newborn period . however , 50% of these patients required ureteric reimplantation after newborn period for febrile urinary tract infections .\nbaradaran et al . also stipulate that delayed primary repair of exstrophy does not compromise the rate of bladder growth .\nhowever , children born with smaller templates will have overall smaller capacities and are less likely to undergo bladder neck reconstruction .\nwhile bladder prolapse and dehiscence have been recognized as major complications of primary be repair , posterior urethral outlet obstruction after bladder closure puts bladder and upper tracts at risk and markedly decreases the success rate of modern techniques of staged reconstruction .\ntherefore , whichever treatment modality is chosen for the newborn with be ; modern type of staged reconstruction , bladder , and urethral closure by penile disassembly in the newborn or urinary diversion , follow - up must be careful and into and including adulthood . in our experience ,\nthe modern staged repair offers a low risk of renal scarring with acceptable continence opportunity with acceptable cosmetic appearance of external genitalia in the males and females .", "answer": "introduction : classic bladder exstrophy ( be ) is a rare malformation of the genito - urinary tract affecting 1:50,000 to 1:100,000 live births . the surgical reconstruction of the be - epispadias complex is challenging for the most experienced pediatric urologists , surgeons , and orthopedists.purpose:to assess the success of staged reconstruction of the be and long - term effects on the upper urinary tract , renal function , and continence.materials and methods : this is retrospective study ; between 1994 and 2013 , 30 patients with be have undergone stage 1 repair at the institute . \n eighteen male patients have been operated for epispadias repair and thirteen patients have undergone guy leadbetter bladder neck reconstruction . \n three patients required augmentation cystoplasty one child is continent after epispadias repair only and one child attained continence after single - stage repair.results:hence , out of 17 patients , 14 are socially continent , four patients require clean intermittent self - catheterization for bladder emptying . \n four patients , who are coming for regular follow - up , are awaiting continence procedure . \n two patients who underwent augmentation cystoplasty are on hemodialysis for renal failure and one child has altered renal function.conclusion:in our experience , the modern staged repair offers a low risk of renal scarring with acceptable continence opportunity with acceptable cosmetic appearance of external genitalia in the males and females .", "id": 48} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n the distribution of sandflies correlated with the appearance of cases of leishmaniasis in endemic regions , especially in forested areas .\nhowever , with human intervention and the disappearance of their natural habitat , some species appear to have adapted to degraded habitats , contributing to expansion of their spatial distribution and the spread of leishmaniasis [ 13 ] .\nthe main factors involved in the transmission of tegumentary leishmaniasis are related to deforestation , urbanization , the presence of domestic animals , and the development of agriculture , particularly the cultivation of cocoa , banana , and coffee .\nwhile some species of sandflies have disappeared , others have become more abundant and have adapted to synanthropic environments by changing their behavior [ 510 ] .\nin particular , this expansion has replaced traditional crops with crops that are more productive , which has led to changes in sandflies populations related to altered patterns of dispersal and spatial distribution of these species in new areas [ 1014 ] , because these changes may involve a greater risk of transmission [ 3 , 15 ] .\nthus , an understanding between habitat variation and sandflies populations is essential , and to examine whether these changes can increase the risk of transmission of leishmania , we studied populations of sandflies in a conserved area and two distinct agroecosystems .\nthe agroecosystems located in the parroquia cao el tigre , zea municipality , merida , venezuela , were studied .\nthese regions have an average elevation of 300400 meters above sea level , covering an area of 135 km , which includes 9,595 inhabitants , a tropical rainforest climate , and temperatures that range between 25 and 30c .\nthe main economic activities of the region are agriculture and cattle . according to methods previously described in the literature ,\nindicators associated with ecoepidemiological levels were recorded using a data sheet that identified the environmental and anthropogenic variables related to the presence of sandflies .\nthese variables included the climatic conditions ( elevation , temperature , and relative humidity ) , the presence of natural or anthropogenic water bodies , dominant vegetation stratum , crops and animals present , and the level of human interference ( e.g. , logging , burning , and use of fertilizer ) .\nthe aspects observed concern the vegetation and the presence of both dwellings and animal shelters .\nthree agroecosystems were selected with varying degrees of ecological disturbance : ( 1 ) a conserved area , predominantly forest , characterized by abundant primary vegetation ; ( 2 ) a fragmented area in which primary vegetation was partially replaced by cocoa crops without management ; and ( 3 ) a disturbed area with complete replacement of primary vegetation , resulting from the degradation caused by human activity related to citrus cultivation , specifically oranges ( figure 1 ) .\ncaptures of adult sandflies specimens were performed for 12-month period , from january 2012 to january 2013 at three agrosystems .\nthe captures were conducted at the peridomicile areas , using one shannon traps , three cdc traps , six sticky traps , and direct suction with an oral grabber .\nsampling was conducted after sunset , when sandflies are most active , between 18:30 h and 20:00 h ; with minimum of one capture by months each collection agrosystem .\nshannon traps were conducted in peridomicile areas with three collectors , the cdc light traps were placed in proximity of houses ( poultry houses , breeding pigs , tree , etc . ) , and sticky strips ( white paper sheets 21.6 27.9 cm coated with castor oil ) were placed indoors or outdoors in proximity of houses .\nthe traps were distributed over 1 ha of the agrosystems and arranged in transect with at least 20 m of distance between each trap . to determine the presence of leishmania promastigotes , the digestive system was extracted via the dissection of live females and examined using phase contrast microscopy at 400x magnification .\nwe then performed rapid identification of fresh sandflies individuals , and body or representative segments were subsequently cleared in nesbitt solution for 24 hours and were prepared and mounted on slides using berlese 's medium to identify females for corroboration of the species by comparative external and internal morphology .\nthe methods used were based on community structure , proportional abundance , dominance index , and margalef 's index which was used to calculate biodiversity .\nan analysis of the different captures among and agrosystems was conducted using a cluster analysis which was performed using pcord.5 software ( license belonging to icae ) .\nthe comparison for the different agrosystems was conducted using analysis of variance ( anova ) which was performed with a level of significance of 0.005 , tukey 's test . to investigate the possible association between species distribution and ecosystems\na simple correspondence analysis was carried out using the ibm spss statistical software package , which is publicly available for download at http://ibm-spss-statistics.softonic.com .\nthe ecoepidemiological characteristics and the degree of disturbance of the 3 agroecosystems are summarized in table 1 .\nthe shannon traps , cdc light traps , sticky traps , and direct suction captured 94.7% , 2.2% , 1.2% , and 0.9% of the sandflies , respectively .\nl. gomezi was the most abundant species in the area , present in all environments studied . according to the abundance values of sandfly specimens collected ,\nl. gomezi , l. ovallesi , l. walkeri , l. trinidadensis , and l. panamensis were the main species identified in the 3 agroecosystems .\nthese species were found at different abundance levels , although l. panamensis was only detected in the conserved forest ( table 2 ) .\ncluster analysis was performed to assess the segmentation of each capture , and we identified 2 groups of homogeneous captures with 46% similarity .\nthe anova results showed significant differences between the populations of sandflies identified in each agroecosystem ( one - way anova , f = 551 , df = 16 , p = 0.000 ) . to further evaluate these differences , a post hoc\ntukey 's test was performed for paired agroecosystems , specifically between forest and cocoa agroecosystems and cocoa and orange agroecosystems ( table 3 ) .\nthe highest values of diversity and species richness occurred in the most conserved agroecosystem , the forest ( 2.26 and 14 , resp . ) .\nmoreover , the values for diversity and species richness decreased with an increasing degree of ecological disturbance , as observed with the cocoa ( 1.80 and 9 ) and orange agroecosystems ( 1.32 and 7 , resp . ) .\nthe dominance level was 0.34 in the forest and increased with an increasing degree of ecological disturbance , with the highest value corresponding to the orange grove agroecosystem ( 0.64 ) ( figure 3 ) .\nthe simple correspondence analysis between sandflies species and agroecosystems identified a strong association between l. gomezi and l. atroclavata with disturbed agroecosystems and a strong association between l. ovallesi , l. walkeri , l. shannoni , l. hernandezi , l. panamensis , l. migonei , l. cayenensis , and l. pilosa with conserved agroecosystems ; species such as l. trinidadensis , l. olmeca nociva , and l. spinicrassa showed no association with any agroecosystem ( : 124.7 ; df = 30 ; p = 0.005 ) ( figure 4 ) . in the conserved agroecosystem ,\nl. gomezi , l. ovallesi , and l. walkeri demonstrated natural infection with leishmania species , which were identified as the subgenera leishmania and viannia .\nhuman encroachment on forest ecosystems is driven by logging and agricultural conversion , resulting in sharp and rapidly moving gradients between the relatively cool and humid primary forest and the cultured land , which show strong insolation , higher temperature , and lower humidity .\ntropical areas are characterized by a great diversity and wide distribution of sandflies fauna [ 19 , 20 ] . in brazil\n, it has been reported that the devastation of natural areas , which includes natural habitats for sandflies , increases the adaptability of these species to environments with human intervention , as observed by the increasing number of cases of leishmaniasis in urban environments .\nit is likely that habitat degradation and climate change greatly impact the abundance and richness of sandflies .\nthe results of this study highlight differences in the sandflies population composition and structure across 3 agroecosystems , characterized by the different degrees of ecological disturbance that were surveyed .\nfew studies on sandflies have focused on this aspect , as most reports have been limited to epidemiological studies and the documentation of naturally infected species .\nin addition , other studies have focused on how the population composition changes in different areas , such as the home and peridomestic or wild environments [ 2224 ] , or according to the type of capture method used .\nthe results are in concert with others who have proposed that changes in habitat may have a marked impact on the sandflies populations [ 510 ] .\nthe relationship between leishmaniasis and agricultural activity has been recorded and the relationship between coffee cultivation and the transmission of leishmania by sandflies has been recorded in venezuela , colombia , brazil , and mexico [ 11 , 2629 ] .\nthis could be explained by the suitability of shade - grown coffee plantations for the resting and breeding of sandflies .\nmoreover , this type of agroecosystem presents high biodiversity and promotes the presence of many vertebrates , which in turn act as reservoirs of leishmania and potential feeding sources for sandflies [ 30 , 31 ] . in this study ,\nthe effect of human intervention was reflected in the disturbed agroecosystems as an increase in dominance and a decline in diversity and species richness , relative to less ecologically disturbed areas such as the conserved agroecosystem , where dominance is lower and diversity and species richness are greater .\nthese results are supported by those of previous studies [ 3 , 21 , 32 ] .\nmost diversity and species richness in the forest , conserved area , could be caused by higher accumulation organic material to accumulate as a result of the decomposition of leaves and vegetation waste lying on the soil favoring larval development .\nenvironments with significantly disturbed wilderness areas cause certain species to adapt to these new spaces , as observed in our study .\nmoreover , our results show that anthropogenic modification can favor certain species to colonize these disturbed environments , such as was reported for l. longipalpis and l. flaviscutellata in urban areas of brazil .\nfew species are able to adapt to high levels of anthropogenic disturbance , consequently , demographic parameters such as mortality and birth rates for each species are affected differently , and ecosystem structure and dynamics are in turn affected ; yet based on the abundance values , our results suggest that l. gomezi was the species with the greatest ability to exploit disturbed environments [ 3 , 35 ] . both l. gomezi and l. ovallesi have been considered as important vectors of leishmania .\nthe type of agroecosystem affected the abundance of l. gomezi and l. ovallesi which have an important effect on the probability of humans being bitten by one of these two vectors .\nl. gomezi has been reported to have a marked preference for biting humans around homes where vegetation is scarce , and this species has also been known to invade the inside of the home [ 36 , 37 ] .\nthese findings suggest a greater risk of transmission of the disease in these areas . the abundance of l. ovallesi , a species that transmits leishmania braziliensis , has also been confirmed as a vector of leishmania mexicana in venezuela , and in conserved areas such as forests ,\na potential natural habitat and fragmented areas with cocoa plantations confirm the association of this species with woody vegetation [ 3840 ] .\nthe sympatric relationship between l. ovallesi and l. gomezi is comparable to what was reported in brazil between l. intermedia and l. neivai , where l. ovallesi is the species with a greater dependence on conserved areas than l. gomezi , predominated near the peridomiciles , indicating a process of adaptation , mainly to this environment of less dense vegetation .\nl. gomezi and l. ovallesi as predominant species of primary forest , as the deforestation extended , there was a tendency for l. ovallesi to disappear , suggesting that this species is more dependent on the primary forest than l. gomezi .\nin the conserved forest agroecosystem , l. gomezi , l. ovallesi , and l. walkeri demonstrated natural infection with leishmania of the subgenera leishmania and viannia , and this seems to indicate that these species may be transmitting the leishmaniasis agent in the forest agroecosystem area .\nif these areas have a greater diversity of sandflies species , it would be expected that there would be a greater coexistence of various species of leishmania , given the specificity between the sandflies vector and leishmania .\nmoreover , the increased abundance of l. gomezi in disturbed agroecosystems indicates that this species has adapted to new environments modified by humans .\nthe altered environments favor adaptation of l. gomezi ; these results suggest that the transmission pattern may be changing .\nthis study provides a basis for further in - depth studies to assess how anthropogenic changes can modulate vector composition and distribution and could also help to explain how this might affect the transmission of tegumentary leishmaniasis in merida and potentially disease risks .\nthese results clearly show that sandflies fauna exhibited changes in species number as well as population structure in degraded environments . as a result\n, changes in the determinants of transmission can lead to the development of new outbreaks .", "answer": "the exploitation of new wilderness areas with crops is increasing and traditional crop substitution has been modified by new more productive crops . \n the results show the anthropogenic disturbance effect on the sandflies population and leishmania transmission in endemic areas of venezuela . \n three agroecosystems with variable degrees of ecological disturbance , forest ( conserved ) , cacao ( fragmented ) , and orangery ( disturbed ) , were selected . \n four methods to sandfly capture were used ; the specimens were identified and infected with leishmania . \n diversity , population structure , anova , tukey test , and simple correlation analysis were carried out . \n shannon traps were able to capture 94.7% of the total sandflies , while cdc light traps , sticky traps , and direct suction just captured 2.2% , 1.2% , and 0.9% , respectively . \n the results showed the effect of ecological disturbance degree on the composition of sandflies and population structure , revealing a dominance level increased but decreased on the diversity and richness of sandflies species in the greatest ecological disturbance area in relation to areas with less organic disturbance . \n environments more disturbed cause adaptability of certain species such as lutzomyia gomezi and lutzomyia walkeri . \n these changes on the composition of sandflies population and structure emerging species could cause increasing of leishmaniasis transmission .", "id": 49} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan estimated 207 million cases of human schistosomiasis have been reported worldwide and about 90% of these live in sub - saharan africa , with nigeria having the highest prevalence .\nschistosoma infections cause significant morbidity and mortality with peak prevalence and intensity of infection occurring between the ages 10 and 20 years and subsequent decline by age 65 years .\nchronic human circulatory system infection by schistosoma haematobium is reported to affect the urinary bladder and is a possible risk factor in the aetiology of cancers of the bladder and the urinary tract system .\ns. haematobium infection has been linked with the development of squamous cell carcinoma of the bladder [ 4 , 5 ] .\ns. haematobium associated bladder damage has been closely linked to the immune reaction elicited against the parasite egg deposited in the bladder which eventually induces chronic inflammation related granulomatous injury .\nschistosomiasis and bladder cancer share common symptoms such as haematuria , dysuria , and pain with micturition .\nthis may prevent early diagnosis of bladder cancer and the resultant severe bladder damage particularly in people living in s. haematobium endemic areas . in nigeria ,\nmost studies have focused on the epidemiology of s. haematobium infection [ 3 , 7 , 8 ] particularly in school - age children , with limited information about the morbidity resulting from urinary schistosomiasis in adults .\nthis study was therefore aimed at determining the prevalence of schistosomiasis and associated bladder pathology in adults living in eggua , yewa , north local government area , ogun state , nigeria .\nthe study was carried out in eggua , a rural agrarian community , between august 2012 and may 2013 .\nit is one of the wards that make up yewa north local government area as previously described .\nit consists of settlements at sagbon , imoto , tata , agbon - ojodu , and igan alade .\ntwo major rivers ( yewa and iju ) flowing through the area serve as the main water source , resulting in high water contact by the inhabitants .\nthese rivers are used for religious , domestic , and entertainment activities which enhance the transmission of schistosomiasis .\nparticipants aged 30 to more than 60 years old from the community were enrolled for the study .\nchildren were excluded from the study in line with the objective of the study to determine the effect of chronic urinary schistosomiasis on adult members of the community .\ninformed consent was obtained from each participant under a protocol approved by the local government and local health officials .\nethical approval for the study was also obtained from the ogun state ministry of health .\nblood ( 5 ml ) and urine specimens were collected from each study participant .\nthe urine samples were collected between 10:00 and 14:00 hours to ensure maximum egg yield .\nthe urine samples ( 10 ml ) were processed for microscopic examination and egg count [ 3 , 10 ] .\nthe eggs were quantified by counting under the microscope and classified as light infection if there were 50 ( 149 ) eggs/10 ml urine and heavy infection if there were > 50 eggs/10 ml urine .\na blind ultrasound examination was carried out on each participant approximately 1 h after drinking potable water ( 0.11.5 litre depending on the age of the participant ) to distend the bladder .\nthe classification of bladder pathology or damage was based on the definition of the who [ 11 , 12 ] and shiff et al . ; the abnormalities assessed included abnormal bladder shape , bladder wall irregularities , bladder masses , presence of polyps , calcification , and presence of hydronephrosis in the kidneys .\nbladder lesions were considered severely abnormal when four of the above conditions or three conditions as well as hydronephrosis were present in a single individual .\nlesions were considered moderate if fewer conditions were seen and negative when no specific lesions were observed .\na structured , pretested questionnaire was used to obtain information about participants ' habits regarding smoking and alcohol consumption , which are determinants of bladder cancer .\nstatistical analysis of data obtained was done using spss version 20.0 ( p < 0.05 ) .\na total of 257 ( 79 males and 178 females ) participants aged 3090 years were screened for s. haematobium infection and associated bladder pathologies .\nthe overall prevalence of s. haematobium in the sampled population was 25.68% ( 66/257 ) , 21 ( 31.8% ) in males and 45 ( 68.2% ) in females .\nthe highest prevalence of infection was observed in participants over 60 years old ( table 1 ) . the majority ( 56/66 ) ( 84.8% ) of those positive for s. haematobium had a light intensity of infection with the egg mean intensity of 16.7 eggs/10 ml urine .\nthe yewa river was the main source of water for most ( 49/62 ) ( 79.0% ) of the participants infected with s. haematobium ( table 4 ) .\nbladder pathologies were observed in 33.9% ( 87/257 ) of the sample population and included abnormal bladder wall thickness ( 39/66 ) ( 59% ) , abnormal bladder shape ( 10/66 ) ( 15.2% ) , bladder wall irregularities ( 15.2% ) , bladder masses ( 1.5% ) , and bladder calcification ( 1.5% ) ( table 2 ) .\nbladder wall thickness , the most common abnormality , was recorded in 46/79 ( 58.2% ) males and 90/178 ( 50.6% ) females ( table 3 ) . among the participants ,\n56 ( 84.8% ) with bladder pathologies also had an existing schistosomiasis infection , 48 ( 87.3% ) of which were light intensity and 8 ( 72.7% ) of which were heavy intensity : = 267.5 , p = 0.001 ( table 5 ) .\nthus , there was an association between urinary tract pathology and the intensity of s. haematobium infection ( = 375.4 , p = 0.001 , table 2 ) . among the participants with light and heavy intensity of s. haematobium infections , bladder wall thickness was the most common bladder structural pathology\nidentified in 33/56 ( 58.9% ) and 6 ( 60.0% ) participants with light and heavy s. haematobium infections , respectively ( table 5 ) . abnormal bladder shape and bladder wall irregularity\nwere seen in 8/56 ( 14.3% ) and 2 ( 20% ) participants with light and heavy infections , respectively ( figures 13 ) .\nhydronephrosis was present in only one participant with light infection , while calcification was identified in only one participant with heavy infection .\nmild bladder pathology was more common than severe bladder pathology in this study and was found in 48 of the participants ( table 5 ) .\nthere was a higher incidence of bladder pathologies among female participants ( table 3 ) ; bladder mass and hydronephrosis were also seen only in female participants .\nthere was no significant relationship between cigarette smoking and bladder pathology in the study ( table 6 ) . among participants with bladder pathology , 29 ( 33.3% ) admitted consuming alcohol while 58 ( 66.7% ) said that they had never consumed alcohol ( table 7 ) .\nthe overall prevalence rate ( 25.98% ) of adults with s. haematobium infection recorded in this study was slightly higher than 20.8% and 20.0% reported in yewa north local government , ogun state , and owan east local government , respectively , in nigeria [ 3 , 13 ] .\nmost ( 81.3% ) of the participants depended solely on the s. haematobium contaminated river water , which could account for the higher s. haematobium prevalence ; and little or no schistosomiasis control ( drug ) intervention targeted to adults has been recorded in this area .\nthe higher frequency of light intensity s. haematobium infection observed in this study could be explained by some level of acquired protected immunity by adults in that community due to chronic exposure to schistosomiasis .\n. found that the proportion of egg - positive individuals falls progressively with age and is a feature in populations with lifelong exposure to the parasite .\ntherefore , chronicity of infections in older people will more likely be difficult to ascertain using egg count method .\nthe higher frequency of mild bladder pathology observed in this study was also similar to another study which observed a higher incidence of mild bladder than severe bladder pathology .\nthis result could be explained by the low number of participants who smoked cigarettes and consumed alcohol ; these conditions may serve as promoting factors either in progression of bladder pathology to cancer or in making the bladder pathology more severe ( table 4 ) .\nin addition , this lifestyle could buttress the possibility of s. haematobium being the principal cause of the reported bladder structural pathology in the study population .\nthe close relationship between the intensity of s. haematobium infection and the presence of bladder abnormalities was similar to previous reports [ 3 , 1416 ] .\nthe presence of hydronephrosis in participants with light infection is however at variance with the report of nmorsi et al . \nalthough hydrocalycosis ( a condition mostly mistaken for hydronephrosis ) was observed in some patients with heavy infection , indicating the likely contribution of this infection to kidney pathology .\nfemales ( 64.7% ) had more structural bladder pathology compared to males ( 35.3% ) .\nthis may be due to higher water contact by females and also to the higher number of female study participants than an indication of a female predilection to bladder pathology .\nhowever , since hydronephrosis and bladder mass or bladder calculi were found together in a female participant , female predilection to bladder pathology may not completely be ruled out . the structural changes to the bladder recorded in this study were in consonance with observations in west madagascar and nigeria [ 3 ,\n15 ] where bladder irregularities and bladder wall thickness were identified as the most common pathologies in individuals infected with s. haematobium . in conclusion , there is evidence that s. haematobium infections may be associated with bladder pathology , on ultrasound examination .\nindividuals with bladder pathologies could have heavy or light intensity of schistosomiasis infection or have no existing infection at all .\nhowever , a long term exposure to schistosomiasis is necessary for the development of bladder cancer\n. further research on the determinants and progress of the bladder pathologies seen in this study population is needed .", "answer": "screening for schistosoma haematobium infection and its possible morbidity was carried out in 257 adult participants in eggua community , ogun state , nigeria . \n parasitological assessment for the presence of ova of s. haematobium in urine and abdominopelvic ultrasonographic examination for bladder and secondary kidney pathology were carried out . \n s. haematobium prevalence of 25.68% ( 66/257 ) was recorded among the participants . \n there was a significantly higher prevalence of 69.2% of urinary schistosomiasis in the females than the prevalence of 31.8% in males ( p = 0.902 ) . \n the intensity of infections was mostly light ( 55 ) ( 21.8% ) compared to heavy ( 10 ) ( 3.9% ) with the mean intensity of 16.7 eggs/10 ml urine . \n structural bladder pathology prevalence among participants was 33.9% . \n the bladder and kidney pathologies observed by ultrasound in subjects with s. haematobium infections included abnormal bladder wall thickness ( 59% ) , abnormal bladder shape ( 15.2% ) , bladder wall irregularities ( 15.2% ) , bladder masses ( 1.5% ) , bladder calcification ( 1.5% ) , and hydronephrosis ( 3% ) . \n infection with s. haematobium was associated with bladder pathology . \n higher frequencies of bladder abnormalities were observed more in the participants with light intensity of s. haematobium infection than in those with heavy infection . \n more bladder pathology was also seen in women than in men , although this was not statistically significant . in conclusion , there is evidence that the development of bladder pathology may be associated with s. haematobium infection .", "id": 50} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe family is the cornerstone of human social support network and its presence is essential in everyone s life . changes inevitably occur in families with illness and hospitalization of a family member . in other words , among the sources of stress for families are accidents leading to hospitalization particularly intensive care unit ( icu ) .\nstatistics show that 8% of hospital beds in the united states are occupied by the intensive care units .\nstress in the family while the patient is in the icu can disrupt the harmony power of the family members and finally , it may causes disturbances in the support of the patient .\nin addition to the various sources of stress in intensive care units such as the patient s fear of death , financial problems , lack of awareness about the environment and etc . , their satisfaction level is another important source of stress for the patient s family .\ntoday , the family needs of hospitalized patients in the icu are summarized in five sections .\nthese factors may include receiving assurance , staying close to the patient , receiving information , feeling comfortable and receiving support .\nhowever , in many cases , the patient s family needs and their expectations in the icu will not be fulfilled which will cause dissatisfaction . since , how families deal with mental stress is the most important components of comprehensive care , it should be known that attention to the family needs of the patients hospitalized in intensive care units could increase their satisfaction and thus a reduction in stress disorders .\nstudies showed that the nurses in particular sections focus primarily on the patient and the disease .\ntherefore , attention to the families should be considered as an important part in patient management .\neffective interventions targeted at the needs and expectations of family members should help to reduce the stress and improve their satisfaction .\nfox et al . stated that the needs of the family members were not often overlooked by the nurses .\nhowever , the nurses spend a lot of time with the patients and their families and are in a good position to assess their needs and plan for meeting these needs with appropriate interventions .\nthe reason of investigating the satisfaction of the families of the patients in the icu is that the patients are facing life - threatening illness experiences and complex treatments , different technologies and different equipment are used for them .\nthese cases could potentially lead to the dissatisfaction of their families . in the meantime ,\nthe families of trauma and neurosurgical patients are more vulnerable than the other groups of patients .\nthey need supports that are more emotional and should be accepted by the icu staff . today , there are many theories expressed that in intensive care units , the patient and his family should be considered as a single unit . by providing care to this unit ,\nthe aim of this study was to analyze the satisfaction of the families of icu patients .\nthe tool of society of critical care medicine s family needs assessment ( sccmfna ) ( which has been validated in 1998 by johnson ) was used in that study .\nthe results showed that most of the family satisfaction was related to the communication and patient care and the lowest level of satisfaction was about the ability of staff to patients family comfort .\nbailey et al . have conducted a study in 2009 with the purpose of investigating the relationship between informational support to families of special care patients and their anxiety and satisfaction .\nthey showed that there is a direct link between the informational support and their satisfaction .\nthe study of fumis et al . in 2008 also showed that the increase in the availability of physicians for giving the information to the patient s family and as well as nurses efforts to provide understandable explanations about the patient s condition to them will increase the patient s family satisfaction .\nthis clinical trial was performed with respect to the existing gap for a study carried out for investigating the interventions for the satisfaction of the patients in the special care units and their families in iran .\nthe purpose of the study was to determine the effectiveness of nursing interventions based on family needs on family satisfaction level of hospitalized patients in the neurosurgery intensive care unit of al - zahra hospital in 2010 .\nthe statistical research community was the families of hospitalized patients in neurosurgery intensive care unit of al - zahra ( sa ) hospital , isfahan , iran from may to september 2010 .\nwith respect to inclusion criteria , the families of 64 patients were selected with simple sampling . after obtaining the informed consents from the hospitalized patients , by using the envelopes , which were prepaid by using a table of random numbers , they were divided into two groups ( intervention and control ) .\nthe inclusion criteria was included as the following cases : to be a first - degree member of the family , to be older than 18 years , willing to participate in the study , having the power to speak and write in farsi , to be hospitalized one day before the study , lack of physical or mental problem in the family member , no responsibility for the care of another patient , introduced as the first person responsible for the patient care .\nobtaining the written informed consent , completion of the questionnaires about demographic information and the families satisfaction were performed in the second day of hospitalization of the patients in icu in both groups .\njohnson questionnaire for the satisfaction of the family of icu patients was used to measure the family satisfaction .\nthe rating of the questionnaire was performed by using the likert scale with four options of 0 to 4 as follows : almost all the time ( 3 scores ) , often ( 2 scores ) , only occasionally ( 1 score ) and never ( zero score ) .\njohnson s questionnaire was the modified type of multer patient s family needs , which was evaluated in various scientific researches and there are extensive evidences for its validity .\nthe interventions were performed in the second and the third day of hospitalization of the patient in the neurosurgery icu by the researcher in the morning shift for the intervention group .\nthus , the researcher provided understandable explanations about the disease to the patient s family and answered honestly to the questions about the patient and the disease .\nthe researcher ensured them for providing the best care in the section and spoke about the prognosis of the disease .\nthe researcher took the family member to the patient s room and gave the necessary information about the room space , equipment , personnel departments and the actions that were done for the patient .\nthe patient family member was contacted if there was a change in the patient condition .\nthey let the family help the patient in some cases of the public health ( such as hand and foot massage and giving food ) .\nlocations of rest , nutrition , prayer room , bathroom and buffet of the hospital were introduced to them .\nthe telephone numbers of hospitals and wards ( and if necessary , the social worker and supervisor ) were given .\nvarious departments and personnel of the hospital were taught to accept the families and communicate with them . the hospital social worker was introduced and if necessary , the patient s family was allowed to express their feelings .\nthese interventions were performed in the evening shift of the second and the third day of the patient reception .\nthe actions were carried out by the fellow researcher . while , for the control group , only the routine work was done . on the fourth day , the satisfaction survey was completed by the selected family member in both of the intervention and control groups .\nstatistical methods used in this study were 2 test , man - whitney , independent student s t - test and paired t - tests .\nthe findings did not show statistically significant difference in the demographic characteristics of the intervention and control groups , such as : age ( p < 0.99 ) , gender ( p < 0.79 ) , marital status ( p < 0.41 ) , educational level ( p < 0.12 ) and relation with patient ( p < 0.54 ) . as shown in table 1\n, there was no significant difference in the mean satisfaction score before the intervention in the intervention and control groups ( p > 0.05 ) .\nthe mean satisfaction score after the intervention in the intervention group was significantly more than the control group ( p < 0.001 ) .\nthe mean satisfaction score in the intervention group after the intervention was significantly higher than before the intervention ( p < 0.001 ) .\nthere was no significant difference in the mean satisfaction score in the control group before and after the intervention ( p > 0.05 ) ( table 2 ) .\ncomparison of mean satisfaction score ( 100 * ) of participants in the intervention and control groups the mean of satisfaction score changes of the studied subjects in the intervention and control groups after intervention\nthe results of the present study showed that the nursing interventions based on the family needs increased the patient s family satisfaction in the neurosurgery intensive care unit of al - zahra hospital .\ndue to the differences in the study design , study population , the number of samples and methods of intervention , it would be difficult to compare the results . in chien et al .\nstudy , the results showed that performing the training based on the patients family needs in the icu , decreased the anxiety and increased their satisfaction . in the study of myhren et al . indicated that effective communication of the staff with the families of icu patients would increase their satisfaction .\nin the study by rosher and robinson , it showed that involving the families in patient care led to increase their satisfaction than before the intervention .\nthe mentioned results were consistent with the results of this study , because all of these interventions were some parts of the interventions performed in this study .\nhowever , the study of steele et al . indicated that clinical training had no impact on the family satisfaction of the patient hospitalized in the icu\n. therefore , there was no statistically significant difference in the satisfaction level in the control and intervention group .\nin this study , it was shown that the use of nursing interventions based on family needs ( confidence , support , information , proximity and convenience ) had significant impact on the family satisfaction of the patient hospitalized in intensive care unit .\nthey should be based on the family investigation and recognition and their priority needs should be determined in order to cause the greatest satisfaction .\nthe icu nurses must also accept their role in the care of patient s family members .\nthe findings of this study could be a basis for performing further studies about family needs of the patients in the icu especially with the different forms of culture and economy .\nconsequently , the increase in family satisfaction of patients can reduce the stress disorders and improve their mental state and ultimately better support of the patient by the family .\nthis study only examined the effect of nursing interventions in the first days of hospitalization on the satisfaction of the families but the effects on the patient s entire hospitalization period has not been assessed . by performing other researches in this field\n, it would be possible to compare the differences in the effects of nursing interventions based on the needs of families in the early days and the whole period of the patient s hospitalization .", "answer": "background : since the family is a social system , the impairment in each of its component members may disrupt the entire family system . \n one of the stress sources for families is accidents leading to hospitalization particularly in the intensive care unit ( icu ) . in many cases , \n the families needs in patient care are not met that cause dissatisfaction . since the nurses spend a lot of time with patients and their families , they are in a good position to assess their needs and perform appropriate interventions . \n therefore , this study was conducted to determine the effectiveness of nursing interventions based on family needs on family satisfaction level of hospitalized patients in the neurosurgery icu.materials and methods : this clinical trial was conducted in the neurosurgery icu of al - zahra hospital , isfahan , iran in 2010 . \n sixty four families were selected by simple sampling method and were randomly placed in two groups ( test and control ) using envelopes . in the test group , \n some interventions were performed to meet their needs . in the control group , \n the routine actions were only carried out . \n the satisfaction questionnaire was completed by both groups two days after admission and again on the fourth day.findings:both of the intervention and control groups were compared in terms of the mean satisfaction scores before and after intervention . \n there was no significant difference in mean satisfaction scores between test and control groups before the intervention . \n the mean satisfaction score significantly increased after the intervention compared to the control group.conclusions:nursing interventions based on family needs of hospitalized patients in the icu increase their satisfaction . \n attention to family nursing should be planned especially in the icus .", "id": 51} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 12-year - old female patient visited the department of oral medicine and radiology , yenepoya dental college , with a complaint of missing anterior teeth since three years ago .\nshe had a history of exfoliation of decidious teeth due to mobility three years ago and there was no eruption of the permanent teeth .\nthere was a history of presence of two mandibular natal teeth which were exfoliated two weeks after birth .\nher parents had no consanguineous marriage , however her elder sibling died of similar medical problem .\nher medical history revealed that she had visited genetic clinic and they have diagnosed her with ellis - van creveld syndrome .\nshe also had dyspnoea because of congenital lobar emphysema for which she had undergone left upper lobectomy when she was one and half year old .\nintraoral examination showed v - shaped notching of the upper lip at the mid line ( fig .\n2a ) , absence of mucobuccal fold in maxillary and mandibular anterior region ( figs .\n2b and c ) , conical shaped teeth , missing mandibular permanent anterior and retained deciduous mandibular canines , and right lateral incisor teeth ( fig . 2c ) .\nchest radiograph showed homogenous opacity in the left upper zone associated with elevation of hilum and left dome of diaphragm suggestive of left upper lobectomy ( fig .\nantero - posterior view of the legs showed genu valgum , hypoplasia of lateral end of tibia associated with medial tibial diaphysial outgrowth called exostosis , and mild shortening of fibula ( fig .\nhand - wrist radiograph showed carpal fusion , postaxial polydactyly , and shortening of metacarpal and phalangeal bone with cone shaped epiphysis .\nthere was fusion of capitate and hamate on the right hand and hamate and triquadral on the left hand ( fig .\na team work of pedodontist , oral and maxillofacial surgeon , and prosthodontist was required to correct the craniofacial and dental defects in this patient .\nsince the patient was in growing phase , the prosthodontist decided to give acrylic partial dentures for the missing teeth .\noral and maxillofacial surgeon performed frenectomy for the high labial frenum as it was hindering the placement of the partial denture .\nellis - van creveld syndrome ( evc ) otherwise known as chondroectodermal dysplasia has autosomal recessive inheritance .\nit is a syndrome found in amish population of pennsylvania in usa , affecting male and female equally.2 familial history may include parental consanguinity or affected siblings or family members .\nour patient was the second child of non - consanguineous and normally developed parents , however her elder sibling had died of similar medical problem .\nthese patients die due to either cardiac problem or respiratory distress.2 our case did not have any cardiac problem , however there was congenital lobar emphysema because of her dyspnoea .\nshe had undergone left upper lobectomy for the same reason when she was one and half year old child .\nthe syndrome affects mainly the bones such as the lower limb with genu valgum , which requires surgical correction .\nthe upper limbs show the characteristic bilateral postaxial polydactyly.3,4 our case had all these limb anomalies .\nother ectodermal features in this syndrome are the absence or hypoplastic features of finger and toe nails , natal teeth , conical shaped or missing teeth , and absence of labial vestibule because of fusion of upper lip to the gingival margin , leading to the notching of upper lip\n. this could be due to the continuation of the normal serrated condition of the gingiva from the third to seventh month in the uterine life of the fetus .\nit is considered as the characteristic and diagnostic feature of this syndrome.5 - 7 all of these features were also present in this case .\nthere are about 40 independent evc / evc2 mutations.8 ruiz - perez and goodship mentioned that the abnormalities in evc syndrome resulted from the tissue specific disruption of the response to hh ligands.9 weyer 's syndrome , asphyxiating thoracic dystrophy , and orofacial digital syndrome should be considered in the differential diagnosis of this syndrome .\nevc syndrome and weyer 's acrodental dysastosis are allelic conditions caused by loss of function mutation in evc and evc2 .\nthese are separated by 2 - 6 kb of genomeric sequence on chromosome 4p16.10 all the features are similar in both conditions except for the fact that there is delay in fusion of mandibular symphysis in acrodental dysastosis.6 patients with evc syndrome and asphyxiating thoracic dystrophy will have identical features in hand , pelvis , and long bones .\npresence of cardiac anomalies , nail hypoplasia , fusion of upper lip to gingiva and neonatal teeth in evc syndrome , and renal failure with hypertension in asphyxiating thoracic dystrophy will help in distinguishing these two disorders from each other.6,11 presence of multiple gingivolabial frenula is similar to evc in orofacial digital syndrome .\nhypoplastic nasal cartilage , moderate mental retardation , fissured tongue , and ankyloglossia helps to differentiate this from evc syndrome.11 in conclusion , the effective management of this syndrome will require a team which includes pedodontist , oral and maxillofacial surgeon , prosthodontist , clinical geneticist , cardiologist , pulmonologist , orthopaedician , urologist , psychologist , pediatrician , and pediatric neurologist . since the oral manifestation is one of the characteristic diagnostic features , and it affects the esthetic problem , speech , jaw growth of the child , the dentists have an important role to play in proper management of such cases .", "answer": "ellis - van creveld syndrome is a rare congenital genetic disorder having autosomal recessive inheritance . \n it is a syndrome affecting the amish population of pennsylvania in usa with prevalence rate of 1/5,000 live at birth . in non - amish population , \n the birth prevalence is 7/1,000,000 . \n the syndrome is characterized by bilateral postaxial polydactyly of the hands , chondrodysplasia of long bones resulting in acromesomelic dwarfism , ectodermal dysplasia affecting nails as well as teeth and congenital heart malformation . \n there were very rare reports of this syndrome in dentistry . \n the present case focuses on the striking and constant oral findings of these patients , which are the main diagnostic features of this syndrome . \n since the oral manifestations affect the esthetic , speech , and jaw growth of the child , the dentists have an important role to play in proper management of such case .", "id": 52} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nafter initial establishment and derivation of human embryonic stem cells ( hesc ; thomson et al . , 1998 ; reubinoff et al . , 2000 )\nfirst the infection free status of the donors has to be addressed , in europe couples are tested before any fertility treatment is offered , but the cells themselves have to be tested , too ( hovatta , 2011 ) .\nsecond , optimized good manufacturing practice ( gmp ) compliant systems must be implemented for derivation , scaling - up , banking of cells , and their corresponding quality assurance controls ( unger et al . , 2008 ; ausubel et al . , 2011 ) .\nthe culture systems currently encounter the problem of suboptimal quality of xeno - free culture constituents . thus strategies are needed to overcome this difficulty ( sidhu et al . , 2008 ) .\nsteps have been taken ; initially , hesc were grown on irradiated mouse feeders , later human fore - skin fibroblast were used ( hovatta et al . , 2003 ) , now we can use gmp compliant coating substrates specially designed for hesc growth ( rodin et al . ,\nsteps were also taken for the generation defined xeno - free gmp compliant medium for derivation and for expansion ( ludwig et al . , 2006 ;\nthe potential of somatic cell reprogramming via expression of specific transcription factors and thus the generation of hesc induced pluripotent stem cells ( hipsc ; takahashi and yamanaka , 2006 ; takahashi et al . , 2007 ) has the advantage that they could be generated from the recipient patients own cells .\nthere is no deep understanding of the effects that the reprogramming events have ; for instance on extracellular signaling ( okita et al . , 2011 ) , and the way that this could lead to immune reaction .\nhence fast reactivity is already present in healthy individuals for controlling any rapidly amplifying cells ( dhodapkar et al . , 2010 ) .\nun - silenced expression of the reprogramming factor oct-4 might then cause undesired immunoreactivity on the transplanted cells .\nimmunoreactivity toward graft - derived hipsc of the same genetic background was also shown in animal models ( zhao et al . , 2011 ) .\nfor successful reprogramming of somatic cells , many epigenetic changes must occur in an adequate manner .\ndna methylation changes during reprogramming must occur in important developmental and oncogenic regions , which increases the oncogenic risk of the reprogrammed cells ( doi et al .\nthere is an additional risk for abnormalities and high tumorigenic potential , especially if c - myc is used as one of the transcription factors ( okita et al . , 2007 ) .\nalso , genetic and epigenetic stability and large - scale genomic rearrangements after reprogramming and subsequent culture ( kim et al .\n, 2010 ; gore et al . , 2011 ; hussein et al . , 2011 ; lister et al . , 2011 )\nit is also important to address the safety of long - term culture , as shown recently ; the occurrence of chromosomal rearrangements in long - term culture of 125 hesc and 11 hipsc ( amps et al . , 2011 ) .\nthere is a consensus that undifferentiated pluripotent stem cells ( psc ) will not be used directly in any clinical transplantations procedure , but instead their psc derived differentiated cells recently , results using hesc derived dopaminergic neurons have shown correct phenotype differentiation and grafting potential given by no tumor formation , maintenance of the grafted cells , and functional recovery in parkinsonian animal models in mice , rats , and monkeys ( kriks et al . , 2011 ) .\nthe protocols designed for this cell replacement assay were optimal regarding the phenotype , quantity of the cells , functionality , and immunological properties .\nintegration of transplanted cells was achieved when single cells were transplanted , the use of proper biodegradable scaffolds must also be considered .\nin addition to this initial report regarding the neural lineage , differentiation protocols for other cell types are needed . even if transplantation in animal models is successful , it is important to generate safety strategies before clinical trials to appropriately remove undifferentiated psc from their psc derived therapeutic cells .\nstrategies such as inserting suicide gene ( drobyski et al . , 2003 ; uchibori et al . , 2009\n) might have controversial outcomes under clinical trials given their safety ( yi et al .\nalternatively , strategies such as removal of undifferentiated cells using antibodies might be safer ( tang et al . , 2011 ) .\nas discussed earlier , an optimal engraftment and cell replacement strategy should account for a minimal immune reaction in the recipient .\nthis immune reaction occurs because the immune system of the recipient recognizes the grafted cells as foreign material or mismatched cellular components and thus generates a cascade of events that ultimately results in destruction and rejection of the grafted cells .\nthis destruction can also compromise the recipient s immune status ( petersen et al . , 1975 ) .\nimmunoreactivity toward the graft is mainly caused by t cell response toward unmatched major histocompatibility complex ( mhc ) ; in humans called human leukocyte antigen ( hla ) .\nif the profile is unmatched , it will result in rejection ( lechler et al . , 2005 ) .\nthis rejection can occur via direct allorecognition of the donor antigen presenting cells ( apc ) or via indirect recognition of apoptotic cells ingested by the recipients apc , in both cases apcs presenting unmatched mhcs ( walsh et al . , 2004 ) .\nseveral groups have studied mhc profiles of hesc and their differentiated cells ( swijnenburg et al . , 2008 ; pearl et al . , 2011 ) .\nfindings are that undifferentiated cells express mhc i antigens , though at low levels compared with somatic cells ; but they do not express mhc ii molecules ( drukker et al . , 2002 , 2006 ; li et al . , 2004 ) .\nduring in vitro differentiation toward germ lineages , embryoid body ( eb ) formation , or teratoma formation mhc i expression increases dramatically ( drukker and benvenisty , 2004 )\n. also culture methods of hesc can change antigen expression levels ( rajala et al . , 2010 ) .\ncareful selection of culture conditions , both for the undifferentiated hesc and for their differentiated derivatives is needed .\nhuman embryonic stem cells adopts the expression of non - human cell surface markers if exposed to such substances during culture ( martin et al . , 2005 ; hisamatsu - sakamoto et al . , 2008 )\nhence , optimal culture conditions must be xeno - free from the initial derivation and onward .\nthese culture conditions must be carefully analyzed and scientific consensus must be achieved in order to raise current methodologies .\nchallenges with the immunoreactivity of the transplantable cells could be addressed by rigorous immunosuppressive treatments . unfortunately , this is not desired , since there is a clear correlation between the length and intensity of exposure to immunosuppressive therapy and post - transplant risk of malignancy and tumor aggressiveness ( gutierrez - dalmau and campistol , 2007 ) .\nan interesting solution is costimulatory blockage of t cell response ( grinnemo et al . , 2006 , 2008 ; swijnenburg et al . , 2008 ; pearl et al . , 2011\n. this immunosuppression strategy will generate tolerance to the grafted cells and thus increase graft survival ; initial pharmaceutical agents have been developed and pending clinical applications to the fda are to give in the near future more information .\nin this mini - review we highlighted the most important areas to be considered under a cell replacement therapy .\nthe possibility of using hipsc derived therapeutic cells in cell replacement therapies requires still long - term studies in non - human animal models addressing the questions of immunogenicity , epigenetic and genetic stability of these cells , and the optimized differentiation of the cells .\nthe importance of profiling immunogenic markers as part of the stem - ness characterization and profiling of cells allocated in stem cell banks must be consider .\nsuch information has to be well protected so that it will not be lost in any given situation .\nadequate culture conditions , supporting correct immunogenicity of the cells under a transplantation assay is also required .\nnext , the management of immunosuppression schemes must aim to a minimal time influencing the immunological status of the recipient . from all the information obtained ,\nthese profiles can then be used in combination with methodologies focused at monitoring the status of the transplanted cells . in a given scenario that undesired cells persist in the transplant , adequate counteracting actions have immediately to be taken .\nsuch possibilities have to be tested and the removal of undesired effects confirmed before starting cell transplantations .\nthe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .", "answer": "human embryonic stem cells ( hesc ) and induced pluripotent stem cells ( hipsc ) are an attractive cell source for regenerative medicine . \n these cells can be expanded to vast numbers and can be differentiated to many desired pluripotent stem cells ( psc ) derived therapeutic cells . \n cell replacement bears promises , but also challenges \n . the introduction of exogenous cells in a recipient must address several different topics ; its safety , the exclusion of tumor formation , the immunological response and possible rejection , the cells cleanliness and their biological quality , and quantity representing the functionality of the psc derived therapeutic cells . \n tumor formation requires the removal of any psc remaining after differentiation . \n immunological rejection can be addressed with immunomodulation of the cells and the recipient . \n cleanliness can be optimized using good manufacturing practice quality systems . at last \n , the functionality of the cells must be tested in in vitro and in animal models . after addressing these challenges , \n precise strategies are developed to monitor the status of the cells at different times and in case of undesired results , corresponding counteracting strategies must exist before any clinical attempt .", "id": 53} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthirty patients with zygomatic complex fractures were treated with one point fixation [ figures 13 ] .\npreoperative peripheral nerve stimulation x - ray preoperative computed tomography scan under general anesthesia , nasoendotracheal intubation was done .\nthe incision can be made from anterior to posterior or from medial to lateral and should extend through mucosa , submucosa , and any buccinators muscle fibers [ figure 4 ] .\nrowe 's zygomatic elevator was then inserted behind the infra temporal surface of the zygoma , and bone was reduced into its correct anatomical position using superior , lateral and anterior force . an audible click and fullness of the cheek together with palpation for normal contour of the zygomatic bone and orbital rim gave an idea about the adequacy of the reduction .\none hand over the side of the face was used to assist in the reduction .\na four hole plate with a gap was fixed with 4 mm 2.5 mm screws on the zygomatic buttress [ figure 5 ] .\nimmediate post operative immediate peripheral nerve stimulation x - ray six months postoperative and peripheral nerve stimulation x - ray\nfor all the patients , immediate postoperative and 6 months postoperative peripheral nerve stimulation x - rays were taken , and the x - rays review successful reduction .\nnone of the patients complained of any paresthesia , bony movements or pain in the frontozygomatic or zygomatic buttress region .\nsince intraoral approach was used , all the patients had an aesthetic facial profile without any unsightly scars .\nthe integrity of the zygoma bone is critical in maintaining normal facial width and prominence of the cheek .\nthe zygomatic bone is a major contributor to the orbit and plays an important role in protecting the eyes .\nzygomatic bone alone is rarely involved in fractures ; usually its articulating surfaces which are maxilla , temporal , frontal and sphenoid bones are also involved .\nthe fractured fragments of a tripod or tetrapod zygomatic complex fracture near these suture lines needs to be restabilized by open reduction followed by fixation .\nstudies suggest that two point gives a considerable stabilization , and three point fixation gives the maximum stabilization .\nhowever other studies suggest that one point fixation for zymatic complex fractures gives an excellent results considering the esthetics and stabilization for simple tripod fractures without any comminution of the zygomatic bone or the lateral orbital wall one point fixation with a single mini plate in the frontozygomatic area through the lateral eyebrow incision have been suggested by many authors .\ni n these cases it was found that when a tripod fracture without any comminution or mild or no displacement can be stabilized very well with a single point fixation in the frontozygomatic area without any complications of diplopia or enopthalmos .\nhowever , zygoma provides the attachment point for muscles of mastication and facial animation , but amongst these , it is the masseter that provides the most significant intrinsic deforming force on the zygomatic body and arch .\nthe integrity of zygomatic buttress is necessary for withstanding the contraction force of the masseter muscle . in 2002\nfujioka et al . \n in vivo studies successfully proved that one point fixation at the zygomaticomaxillary complex gives three point alignment and sufficient rigidity when the fractures are not comminuted . in 2011\nkim et al . found out that lateral eyebrow incision for mini plate fixation at the frontozygomatic area led to unaesthetic scar and few patients underwent plate removal through a second surgical re - entry through the existing scar of the lateral eyebrow incision which further enhanced the unsightly scars and compromised facial esthetics . since the skin over the lateral eyebrow region is thin there are more chances of palapation of the mini plates after fixation , and it may lead to pain . as early as in 1994 tarabichi et al .\nproved that in vitro studies are misleading regarding the mini plate fixation along the orbital margins and successfully applied transsinus reduction through anterior comminuted sinus wall . in 2012 kim et al .\nsuccessfully reduced the zygomatic complex fractured fragments through intraoral approach and gained sufficient rigidity and excellent esthetics with one point fixation at the zygomatic buttress region .\nwe also found that one point fixation with a single mini plate at the zygomatic buttress through intraoral incision provided excellent stability and esthetics in the selected cases of simple zygomatic complex fractures without any comminution of the zygoma or the lateral orbital rim without or with minimal displacement and none of our patient complained of pain or palpation or bony movements in the postoperative study period of 6 months rather they were happy to get operated without any unaesthetic facial scars .", "answer": "for decades , facial beauty and esthetics have been one of the most important quests of the human race . the lateral prominence and convexity of the zygomatic bone \n makes it the most important bone for providing the aesthetic facial look and sets up the facial width but at the same time this prominence and convexity makes this bone more vulnerable to injury . \n zygomatic complex fractures or tripod fractures are the second most common fractures after nasal fractures among facial injuries . \n several studies have been undertaken regarding the reduction and fixation of zygomatic fractures with mini plates and screws . in 2002 \n fujioka et al \n in vivo studies successfully proved that one point fixation at the zygomaticomaxillary complex gives three point alignment and sufficient rigidity when the fractures are not comminuted . in this article , \n 30 cases have been reviewed with one point fixation of zygomatic complex tripod fractures at the zygomatic buttress through keen 's intraoral approach along with advantages and disadvantages .", "id": 54} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n parent - of - origin effects is a broad term that encompasses two distinct phenomena \nparent - of - origin effects on transcription , and parent - of - origin effects on mutation rates .\na parent - of - origin effect on transcription , or genomic imprinting , results from epigenetic modification of the genome which , in turn , results in unequal transcription of parental alleles . for these imprinted genes , expression of the alleles is dependent upon the sex of the parent from which they were inherited ( 1 ) . a parent - of - origin effect on mutation rate\n, however , refers to the preferential occurrence of some spontaneous mutations in either the father 's or the mother 's germ line .\nthe mechanisms by which these spontaneous mutations arise depend upon the parental germ line in which the mutation occurred .\nfor example , base substitutions , arising from errors during replication , tend to be paternal in origin , owing to the greater number of cell divisions in spermatogenesis as compared with oogenesis ( 2 ) .\noocytes are arrested in prophase of meiosis i until sexual maturity , when one oocyte per month is selected to resume the cell cycle .\nit is thought that the longer the oocytes are arrested in meiosis , the greater the chance for a nondisjunction event to occur ( 3 ) .\nadvanced parental age seems to influence the development of some , but not all , of these mutations ( also referred to as the paternal or maternal age effect ) ( 2 ) .\nin 1998 , the catalogue of imprinted genes and parent - of - origin effects was first published ( 4 ) .\nthis catalogue served as the basis for the development of a more comprehensive , searchable , online database , made publicly available in 1999 .\nthe original database included 41 imprinted genes , and other parent - of - origin effects , including some records on the parental origin of spontaneous mutations ( 5 ) .\nwe have added recently a comprehensive section on spontaneous mutations that show a bias with respect to their parental origin .\nthis new part of the database can be searched according to mutation type , disorder , chromosomal location , gene name and inheritance pattern .\noutcomes of the search are presented in a tabular format with the following information : disorder , inheritance pattern , incidence of disorder , gene name , chromosomal location , evidence of a paternal or maternal age effect , mutation type and any recurrent mutations associated with a parent - of - origin effect , number of paternal mutations , number of maternal mutations and pubmed reference ( e.g. table 1 ) . in the case of base substitutions , data are separated according to the type of base substitution ( missense mutation , nonsense mutation or splice site mutation ) , whether the mutation is a transition or transversion mutation , and whether the base substitution falls within a cpg dinucleotide . for deletions and insertions , the distinction is made between large deletions and insertions ( > 20 bp ) and small deletions and insertions ( < 20 bp ) .\nthis size distinction is made based upon the possibility of different mechanisms contributing to these different types of mutations , and therefore potentially different parental origins ( 2 ) . in general , large deletions do not appear to have a parent - of - origin effect , whereas small deletions tend to be more paternal in origin .\ncurrently , > 1700 mutations with a parent - of - origin effect are catalogued in this database .\nthe other major section of the database includes known imprinted genes and observations of other putatively imprinted genes .\nof the 464 database entries , 152 entries describe 85 unique imprinted genes in humans , mice , cattle , sheep , pigs , rats and marsupials , as well as 14 genes for which the evidence of imprinting is conflicting or provisional .\nan additional 186 entries report parent - of - origin effects in the transmission or linkage of simple and complex genetic conditions including human diseases and animal quantitative traits .\nthe imprinted gene and parent - of - origin effect database is housed at the university of otago in dunedin , new zealand and can be accessed at .\nthe database is maintained by the corresponding authors who welcome submissions and comments and is updated as new literature is published .\nsubmissions to the imprinted gene database should be directed to i.m.m . and submissions to the parental origin of de novo mutations database\nexample of report for parental origin of de novo mutations showing base substitutions within a cpg dinucleotide ad , autosomal dominant ; xd , x - linked dominant ; xr , x - linked recessive ; p , point mutation ; ms , missense mutation ; ns , nonsense mutation ; cpg , mutation in a cpg dinucleotide ; ts , transition mutation ; tv , transversion mutation .", "answer": "the imprinted gene and parent - of - origin effect database ( ) consists of two sections . \n one section catalogues the current literature on imprinted genes in humans and animals . \n the second , and new , section catalogues current reports of parental origin of de novo mutations in humans alone . \n the addition of a catalogue of de novo mutations that show a parent - of - origin effect expands the scope of the database and provides a useful tool for examining parental origin trends for different types of spontaneous mutations . \n this new section includes > 1700 mutations , found in 59 different disorders . \n the 85 imprinted genes are described in 152 entries from several mammalian species . \n in addition , > 300 other entries describe a range of reported parent - of - origin effects in animals .", "id": 55} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nviruses are divided into two similar - sized groups depending on whether the virus particle contains dna or rna , and , as causes of human fatality , rna viruses are by far the more important ( 1 ) . new viral diseases continue to appear as a result of several changes in human activity : travel , population growth , interaction with wild habitats etc .\nwell - known novel , or emergent , rna diseases include severe acute respiratory syndrome ( sars ) ( 2 ) , human immunodeficiency virus 1 ( hiv-1 ) ( 3 ) , and may come to include avian influenza h5n1 virus ( 4 ) .\nthese emergent diseases are an important factor behind the increase in the number of genome sequences that ncbi treats as representing new species ( figure 1 ) . in 2005\n, more than 200 new virus species were submitted to genbank ( more recent dates are less reliable because there is typically a delay between submission and public availability ) . as more emergent viruses appear , it is important to have a site that allows their genomes to be compared to those of known viruses . the origin of most major infectious diseases is unknown because of our ignorance of the diversity of pathogens in wild animals .\nthis restricts our ability to both predict risks and develop treatments ( 5 ) . \n\ndates are the earliest given in the accession ( either of submission or publication ) .\nsubmissions after 2006 are excluded because accessions are made public typically only following publication and thus the frequency of submissions is more recent time periods is underestimated .\ndates are the earliest given in the accession ( either of submission or publication ) .\nsubmissions after 2006 are excluded because accessions are made public typically only following publication and thus the frequency of submissions is more recent time periods is underestimated . despite some advances ( 6,7 ) ,\nthe evolutionary history of rna viruses is in general poorly known , especially the deep phylogenetic relationships between virus families ( 8,9 ) .\nwe believe that one of the reasons for this is a lack of easily available translated genes and genomes for all species , and the lack of aligned genome sequences representing different isolates of the same species .\nin addition to the need to facilitate greater comparative analysis of rna viruses is the need to link together the existing virus web sites and their underlying databases .\nthere are many web sites that provide genomic data , tools for genetic analysis and/or biological information for some viruses ( see links on our site home page ) .\nthe rna virus database is intended to complement these other sites by providing basic genomic information and tools for all rna viruses and linking the user to more specialist sites , where they exist , e.g. for hiv-1 and hepatitis c virus ( hcv ) , we provide links to sites such as the los alamos laboratory on the main page for each of these viruses ( find by typing hiv-1 or hcv into the search window in the top toolbar ) . for such viruses ,\nwe do not duplicate the work of other groups by attempting to display the available diversity of genomes .\nwe intend that the rna virus database should develop further as a hub for other sites and we therefore encourage other workers to contact us with details of their sites that they wish linked to ours . also , we encourage workers to adopt a virus and improve and/or expand the information that we provide for individual species . this can be done by emailing us or getting involved directly in developing the database , which is an open source project available at our googlecode site ( http://code.google.com/p/rnavirusdb ) . some of the data and tools on the rna virus database can be found elsewhere , but not all of them can\n, e.g. ncbi 's genome site provides genomic overviews of virus species and pairwise alignments of other isolates to the reference sequence , but it does not provide multiple alignments or complete translated genomes as we do .\nsimilarly , its general entrez site provides pair - wise alignments of the query sequence and similar sequences in the database , plus a phylogenetic tree calculated from those distances ; however , no multiple alignment is built .\nwe also corrected the ( few ) errors in the genbank entries , and our database records features such as rna editing ( 10 ) that make genome translation problematic .\nwe have , therefore , created the rna virus database as a user - friendly site devoted to rna viruses , providing essential genomic data and tools ( discussed in more detail below ) and links to the other virus web sites .\nprovide multiple whole - genome alignments , gene and whole - genome translations for all rna virus speciesidentification and taxonomic searching facilityguidance to other web resources .\nprovide multiple whole - genome alignments , gene and whole - genome translations for all rna virus species identification and taxonomic searching facility guidance to other web resources .\nwe provide multiple alignments of whole genomes ( as nucleotides ) for all species where genbank contains multiple representatives .\nour database , thus , currently has multiple alignments for approximately half the species ( available from the main page of any virus species under \nthese alignments were made by downloading from genbank all complete ( or near - complete ) genomes using the bioperl genbank modules ( 11 ) .\naccidental mismatches were excluded by performing a preliminary alignment using blastalign ( 12 ) , which is designed to cope with non- or poorly homologous sequences and reports such matches .\nthe sequences that showed clear homology to the ncbi reference sequences ( we used a cutoff of a maximum of 40% of positions being represented by gaps in the blastalign alignment ) , up to a maximum of 50 , were then aligned using clustalw ( default parameter values ) ( 13 ) . for species for which we have at least three sequences ,\na neighbor - joining tree was then constructed using paup ( with hky - adjusted genetic distances ) ( 14 ) , and this tree is displayed both as a pdf [ via the treegraph program ( 15 ) ] and using figtree , which is a new java - based tree - drawing application created by one of us ( rambaut , a . , unpublished data ) .\nour site allows virus nucleotide or amino acid sequences submitted by the user to be identified or , if the query is a new species , its closest relative to be found .\nin addition , the genomic location of any matched region of the library sequences is shown .\nfor this we use ncbi 's suite of blast programs ( 16 ) ( go to the blast link on the toolbar of the home page ) . once the most closely related reference species has been located , the query sequence can then be placed into a whole - genome multiple alignment for that species ( where such an alignment is present ) in order to show the query 's phylogenetic relationships to the genomes in our database ( go to \n( i ) a blast of the query to the reference species sequence provides coordinates from the resulting pair - wise alignment .\nthese coordinates are then used to select homologous regions from the reference multiple alignment , and a new multiple alignment is then built using clustalw along with a phylogenetic tree using paup as described above .\n( ii ) blastalign ( described above ) is used to generate a new multiple alignment using the query sequence plus the sequences from the reference multiple alignment . \n\nfigure 2.screenshots illustrating use of the rna virus database to investigate a submitted virus nucleotide sequence .\nscreenshots illustrating use of the rna virus database to investigate a submitted virus nucleotide sequence .\nisolates , includes the biological data of the isolates used in the whole - genome multiple alignments [ except for hiv-1 , hcv and hepatitis b virus ( hbv ) , where we used manually built multiple alignments ; for these three species , accession numbers for the isolates are given in the supplementary data as accessionhivhcvhbv.xls ] .\nwe provide amino acid sequences for all virus genes ( or , more strictly , for all open reading frames ) plus complete translated genomes for each virus species ( go to \nthe translated genomes are intended to facilitate phylogenetic analysis of more distantly related viruses ( 9 ) .\none feature that makes annotation of rna viruses difficult is that most species have some gene overlap ( 17 ) , i.e. where the same nucleotides code for two different genes by being read in two different frames .\nwe , therefore , allow the user to select from three possible options for dealing with this feature : ( i ) have overlapped regions excised from the translated genome , ( ii ) have one only of any overlapped amino acid sequences represented or ( iii ) have all the amino acids sequences present , with overlapped sequences placed sequentially ( and thus the nucleotides represented twice ) . using a key word search of the genbank entries , and a standard reference work ( 18 ) where this did not reveal a match ,\nthe rna virus database is a php web application on top of a mysql database .\nphp is available at http://www.php.net , but should come pre - installed on unix machines .\nall data have been taken from the ncbi 's genome and nucleotide sites at the following two urls . \n\ntable names are in large bold font and interlinking column names are in small regular font . relationships of tables in the underlying mysql database .\ntable names are in large bold font and interlinking column names are in small regular font .\nspecies names , nucleotide sequences and accession numbers were downloaded directly from genbank using bioperl modules , while further details of the virus gene coordinates , taxonomic affinities etc.were subsequently extracted from the flatfile of all genbank entries that can be downloaded from the ncbi genome site ( 19 ) .\nour approach was to treat all entries in the ncbi virus genome sites as species and to follow their taxonomic classification , although we only give virus type ( e.g. single - stranded positive - sense , retrotranscribing ) , family and genus at our site .\nwe , therefore , follow ncbi 's inclusion of hepadnaviruses , which include hbv , and caulimoviruses among the rna viruses despite their mature virion containing dna rather than rna ( their possession of reverse transcriptase clearly places them biologically and evolutionarily among the reverse - transcribing group of rna viruses ) .\nthe php scripts can be accessed using subversion ( http://subversion.tigris.org/ ) from our googlecode site at http://code.google.com/p/rnavirusdb .\nthe mysql database ( a gzipped 16 mb dump ) may also be downloaded from the same site for installation on the user 's computer if required .\nif required , the database can subsequently be updated by other users following instructions and perl scripts given in the supplementary material ( perl_scripts.tar ) .\nthis updating involves a series of short intervening manual steps ( we find that complete automation of such processes is inefficient ) .\nwe intend to update the database on at least a 6-monthly basis in order to include newly discovered viruses , and are currently working to incorporate biological and epidemiological data .\nas discussed in introduction , we are keen to collaborate with other groups over further developments of our database .\nwellcome trust ( to r.b . ) ; eu marie curie fellowship scheme ( to t.d.o . ) ; the royal society ( to a.r . )", "answer": "the rna virus database is a database and web application describing the genome organization and providing analytical tools for the 938 known species of rna virus . \n it can identify submitted nucleotide sequences , can place them into multiple whole - genome alignments ( in species where more than one isolate has been fully sequenced ) and contains translated genome sequences for all species . \n it has been created for two main purposes : to facilitate the comparative analysis of rna viruses and to become a hub for other , more specialised virus web sites . \n it is available at the following four mirrored sites . \n \n http://virus.zoo.ox.ac.uk/rnavirusdbhttp://hivweb.sanbi.ac.za/rnavirusdbhttp://bioinf.cs.auckland.ac.nz/rnavirusdbhttp://tree.bio.ed.ac.uk/rnavirusdb", "id": 56} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe online version of this article ( doi:10.1007/s13555 - 015 - 0084 - 3 ) contains supplementary material , which is available to authorized users .\nfinasteride 1 mg is used successfully all over the world for the treatment of androgenetic alopecia in male pattern baldness .\nvarious clinical trials have established finasteride s efficacy in adult men with predominant vertex , anterior and midscalp region [ 2 , 3 ] . on average ,\ncommon side effects are loss of libido , erectile dysfunction and decreased ejaculate volume . these side effects were found in less than 0.5% of patients . to assess the huge difference [ 2 , 11 ] in reporting the side effects\n, we conducted a 2-year randomized , questionnaire - based research study on patients receiving finasteride 1 mg tablets for androgenetic alopecia .\nfor this , we used a questionnaire based on the international index of erectile function ( iief ) ( supplementary table 1 ) .\nthis checks five domains : erectile function , orgasmic function , sexual desire , intercourse satisfaction and overall sexual satisfaction .\na higher iief score indicates better sexual function and low score ( below 25 ) indicates erectile dysfunction .\nthe aim of the present study was to evaluate an age - matched comparison and evaluation of sexual function in patients treated by finasteride 1 mg for early androgenetic alopecia by using iief .\ninclusion criteria were age 1840 years , who came for an outpatient consultation for male pattern androgenetic alopecia , which was diagnosed using the norwood\n hamilton s grading of male pattern alopecia with grade 3 to 5 on treatment with finasteride 1 mg , with good physical health .\nexclusion criteria were patients being treated for various other causes of hair loss other than androgenetic alopecia .\nthose selected patients were briefed about the iief questionnaire and , with their consent , the questionnaire was provided for completion .\na mean duration of approximately 16 weeks of medication was consumed by the patients at the time of answering the questionnaire .\nour controls were 586 patients who attended outpatient consultation for various other non - hair related diseases such as psoriasis vulgaris , lichen planus , allergic contact dermatitis , irritant contact dermatitis , nail disorders , etc .\nthe resultant scores of erectile function domain and iief domain of both the study group taking finasteride 1 mg and their age - wise control group were analyzed with the ibm software package ( spss statistics , ny , usa ) . all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .\nboth the study group and controls were asked to answer the iief questionnaire anonymously to avoid any identity on sexual weakness .\nthe results were compared in an age - wise manner . comparing the age - wise finasteride - consuming patients and the control group ,\nthere was no statistical difference between the groups regarding their sexual function in total iief score or in any of the five domains mentioned .\n1 ) show the scores in the erectile function domain ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls.fig . \n1age controlled 3d graphs showing the scores of domain in erectile function ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls with age and scores both depicted in y axis age controlled 3d graphs showing the scores of domain in erectile function ( a ) and international index of erectile function domain ( b ) in patients on finasteride and their controls with age and scores both depicted in y axis\nthe main mechanism in androgenetic alopecia is miniaturization of hair follicles from terminal to vellus hair due to the effect of androgen , especially dihydrotestosterone .\ntestosterone is converted by 5 alpha reductase to 5 alpha dihydrotestosterone , which is five times more potent than testosterone .\nthis dihydrotestosterone binds to the androgen receptors of the genetically marked hair follicle and leads to miniaturization of that hair follicle .\nfinasteride is an azasteroid type 2 isoenzyme , 5 alpha reductase inhibitor , which inhibits dihydrotestosterone conversion from testosterone .\nthis type 2 isoenzyme is present in the hair follicles and its activity is important in controlling the end organ hyper - reactivity causing androgenetic alopecia .\nobservation of eunuchs and prepubertal boys highlighted the role of testosterone in the induction of androgenetic alopecia .\ntherefore , it is evident that finasteride should not cause any side effects , relating to sexual health , as there will be no decrease in the quantity or quality of the testosterone level .\nhowever , clinical trials conducted by leyden et al . and kaufman et al . \nresulted in 2% of patients experiencing sexual side effects such as the loss of libido , erectile dysfunction and decreased ejaculate volume . in this study\n, patients taking finasteride 1 mg for androgenetic alopecia and the control group were provided with the iief questionnaire and their responses analyzed .\nthe results indicated that erectile and sexual function was not reduced compared to the controls .\nso , not only theoretically , finasteride was found to be a comparatively safe drug in this indian male population .\nthis study was conducted in the indian context on the basis of the iief and the european study by tosti et al . .\nfurther studies should be conducted in a multi - center , double - blind manner .\nin both our study and the study conducted by tosti et al . , sexual and erectile function of those subjects who were orally treated with finasteride was not reduced compared with their age - related controls .\nsupplementary material 1 ( pdf 301 kb ) supplementary material 2 ( docx 19 kb )\nall procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .\nthis article is distributed under the terms of the creative commons attribution - noncommercial 4.0 international license ( http://creativecommons.org/licenses/by-nc/4.0/ ) , which permits any noncommercial use , distribution , and reproduction in any medium , provided you give appropriate credit to the original author(s ) and the source , provide a link to the creative commons license , and indicate if changes were made .", "answer": "introductionfinasteride is one of the most common drugs used in androgenetic alopecia . \n the literature discusses the sexual side effects of the drug ; however , in practice there is little evidence to support this . \n the aim of the present study was to investigate the sexual dysfunction in patients taking finasteride 1 mg for androgenetic alopecia.methodsa questionnaire , based on the international index of erectile function , was given to approximately 586 patients with androgenetic alopecia who were being treated with finasteride 1 mg for an average of 16 weeks . \n these patients were compared to an age - related control group who were attending the dermatology out patients department for various other skin ailments not related to hair disorders.resultsstatistical analysis of the results showed no significant difference in the scores between patients taking finasteride and the control group.conclusionanalysis showed no significant difference in sex - related problems with that of patients taking finasteride and age matched controls , suggesting that sex - related issues are not a side effect of finasteride.electronic supplementary materialthe online version of this article ( doi:10.1007/s13555 - 015 - 0084 - 3 ) contains supplementary material , which is available to authorized users .", "id": 57} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsystemic chemotherapy is the main treatment modality in the management of patients with metastatic disease . after chemotherapy ,\noncologists evaluate tumor response by observing tumor behavior , i.e. growth , reduction or stability in its dimensions [ 2 , 3 ] . nowadays\n, tumor response to therapy as determined by imaging methods is generally used to inform decisions regarding either maintenance or interruption of treatment . in the late 1970s the world health organization ( who ) introduced a standard assessment of tumor response , proposed by miller et al . and adopted internationally , defining objective responses of lesions measurable in two dimensions , such as pulmonary metastasis assessed by x - rays .\nthis evaluation is performed by comparison of tumor area , the sum of all lesions greater perpendicular diameter products , measured in a planar image .\nmore recently a new set of guidelines has been introduced by the response evaluation criteria in solid tumors ( recist ) group with the purpose of reviewing the former criteria and better standardizing response evaluation .\nthis model uses a unidimensional approach taking the sum of the longest diameters instead of the sum of the areas . with the introduction of cross - sectional imaging methods ,\nthe number of measurable metastatic lesions detected in a single patient has increased dramatically , and most oncologists ( as well as study protocols ) recommend the use of one lesion or a few representative lesions to evaluate response in individual patients with multiple lesions .\nmetastatic nodules are not uniform and consist of a heterogeneous cell population with diverse biological behavior that could account for differences in chemotherapy response . a wide range of growth patterns in pulmonary metastases of patients not previously submitted to treatment has been observed .\nthis variation in behavior , if observed in patients being evaluated for chemotherapy response , could influence the response perception .\nthe selection of one or a few nodules , instead of including all identifiable nodules in the response evaluation , could lead to misevaluation and consequently to the continuity of ineffective treatment or the interruption of potentially effective therapy . the present study used ct to quantify the variation in tumor response of pulmonary metastases of solid tumors of varied histology in individual consecutive patients that were submitted to ct studies in order to evaluate response to chemotherapy .\nwe submitted each pulmonary nodule individually , as if it were a solitary metastasis , as well as all the nodules of the same patient combined , to both the who and the recist criteria and compared the response evaluations in each setting .\nwe prospectively evaluated two consecutive chest ct scans of patients with the diagnosis of solid tumor and pulmonary metastases receiving systemic chemotherapy and being routinely evaluated for tumor response .\nwe included in this study 41 chemotherapy response evaluations in 33 patients ( 20 women and 13 men ) , with ages ranging from 14 to 81 years ( median 46 years ) . in eight patients\nthe attending physician ( department of clinical oncology ) established the diagnosis of pulmonary metastases usually by the presence of new pulmonary nodules and progression of metastatic disease and the type of chemotherapy used .\nthe interval between the ct evaluations varied from 1.25 to 8.8 months ( median : 3.9 ; mean ( sd ) 3.8 ( 1.6 ) months ) and the number of cycles varied from 2.0 to 6.0 cycles ( median : 4 ; mean sd : 3.7 1.2 cycles ) .\nhelical scan techniques were performed on ct prospeed and ct hispeed scanners ( general electric ) .\nthe slices obtained were contiguous with 7 mm thickness and a pitch of 1.5 or less .\nthe two larger perpendicular diameters on the axial plane were measured in images printed in lung windows .\nthe number of nodules in an individual patient varied from 2 to 69 ( median : 7 ; mean sd : 13.8 15.0 nodules ) .\nthe nodules initial larger diameter ranged from 2 to 82 mm ( median : 10 ; mean sd : 11.6 8.5 mm ) . in each set of ct scan examinations performed to assess tumor response to chemotherapy , who and recist criteria classified each nodule individually . for the patient s response evaluation a modified version of the who and recist criteria was used by considering the sum of measurements of all pulmonary nodules in each patient to better represent the total tumor volume change for each patient .\nthe bidimensional who criteria of tumor response categories are : ( a ) partial response when area reduction is 50% or more ; ( b ) stable disease for a reduction of less than 50% or an increase less than 25% ; and ( c ) disease progression for an increase of 25% or more .\nthe unidimensional recist criteria of tumor response categories are : ( a ) partial response if linear larger dimension reduction is 30% or more ; ( b ) stable disease for a reduction less than 30% or an increase less than 20% ; and ( c ) disease progression for an increase of 20% or more .\nthe disappearance of the lesion(s ) is considered a complete response by both assessment criteria and both consider the presence of any new nodule as progression of disease , independent of the behavior of any other nodule .\nthe following parameters were determined : ( a ) individual nodule response rate evaluation ; ( b ) response evaluation for each patient , as a whole , according to the who and the recist criteria ; ( c ) intra - individual distribution of response for every patient s nodule ; and ( d ) the proportion of nodules evaluated differently from the patient s response , taking the sum of all nodules into consideration .\nthe nodules response category distributions for different types of cancer , chemotherapy , and initial number of nodules were compared by chi - square test .\nthe agreement between both response evaluation criteria was calculated by the kappa - interrater agreement index .\nhalf ( n=283 ) of the nodules showed a reduction in size considering only the larger measured diameter , while 126 ( 22% ) remained unaltered comparing both ct scan studies and 157 ( 28% ) increased in size . according to the who criteria , 113 ( 20% ) had a complete response , 66 ( 12% ) had a partial response , 258 ( 46% ) were stable and 129 ( 23% ) progressed . using the recist criteria , 134 nodules were considered measurable as having a diameter twice the size of the slice thickness utilized ( > 14 mm ) .\nof these , 22 ( 16% ) nodules had a complete response , 17 ( 13% ) a partial response , 67 ( 50% ) were stable and 28 ( 21% ) progressed .\nclassification was different by the two criteria in 13 ( 10% ) of the 134 measurable nodules .\nthe kappa interrater agreement for both criteria evaluations was 0.85 ( table 2 ) . evaluating the patients response , taking into account the sum of all nodules , by the who criteria\n, one patient was classified as having complete response , five partial response , 15 stable disease and 20 progressive disease ; and by the recist criteria one patient was classified as having complete response , five partial response , 16 stable disease and 19 progressive disease .\nthe kappa interrater agreement for both criteria evaluations was 0.90 ( table 3 ) . \nthe intra - individual variation for metastases response evaluation was quite diverse by both criteria , with no relation to type of cancer , chemotherapy or number of nodules . by the who criteria : from the total of 41 response evaluations ,\nall the patients nodules had the same response classification in four ; in 16 evaluations there were nodules in two distinct classifications ; in 12 three different classifications ; and in seven , nodules in the four possible categories ( fig .\n1 ) . by the recist criteria : measurable nodules were present in 33 of the 41 response evaluations ; in seven there was only one nodule ; in 11 all the patients nodules had the same response classification ; in 12 evaluations there were nodules in two distinct classifications ; and in three evaluations there were nodules in three different classifications ( fig .\neighteen patients presented 82 new nodules observed at the second ct scan , varying from 1 to 21 per patient ( median 2 , mean 4.8 ) , in a proportion of the initial total number of nodules ranging from 5% to 525% ( median 25% , mean 75% ) . by the recist criteria , in one of the 19 patient evaluations resulting in disease progression no new nodule was present and in 14 a new nodule was the sole criterion for disease progression classification ( table 4 ) . by the recist criteria , the proportion of measurable nodules classified differently from the patient evaluation , taking the sum of all measurable nodules into consideration , varied from 0% to 100% ( median : 25% ; mean sd : 30% 33% ) . in a patient with three lung metastases ,\nthe patient evaluation by comparison of the sum of diameters of the three nodules resulted in partial response . in 15 evaluations\nthere were measurable lesions and there were no new nodules ; when the measurable response was the only considered factor , the proportion of measurable nodules classified differently from the patient evaluation , taking the sum of all measurable nodules into consideration , varied from 0% to 100% ( median : 33% ; mean sd : 35% 35% ) .\nafter chemotherapy , evaluation of tumor response is obtained by observing the progress of lesion size .\ndifficulties arose when the number of lesions per patient that could be evaluated increased , mainly after the introduction of cross - sectional imaging methods .\nnowadays most radiologists and oncologists use only one lesion or a few representative lesions to evaluate tumor response in patients presenting with multiple nodules .\nthus , it is important to know the intra - individual variability of response rate evaluation for different tumors in the same patient . clinically , the response rate of solid tumors has been calculated by taking the tumor diameters in observations separated by the treatment , and by determining tumor shrinkage , stability or growth . for many years\nthe world health organization criteria for treatment response evaluation have been the criteria used by most oncologists and in most clinical trials .\nmore recently , several organizations involved in clinical research have reviewed these criteria on the basis of experience acquired since they were introduced and a new set of guidelines has been developed with a model by which response rates could be derived from unidimensional measurement lesions instead of the former bidimensional approach . according to this model , the use of only one lesion dimension simplifies the task of evaluating tumor response and correlates well with the lesion s area , previously used .\nthe recist group tested their criteria in several historical study protocols and obtained good correlation with the who criteria .\nmore recently , studies have shown both good and poor correlation between the unidimensional and bidimensional response evaluations [ 8 , 9 ] . in this present study a high correlation between the who and the recist criteria in the evaluation of individual nodules and patients was achieved .\nthe advantage of using the recist criteria is the simplicity of taking only one measurement per lesion .\nnowadays , the best method of assessing tumor response in most clinical situations is ct scan , leading to detection of a larger number of lesions , with smaller diameters , and more precision on measuring when compared to other methods [ 10 , 11 ] .\neven though pulmonary metastases evaluated by ct scan should be one of the best scenarios in terms of measurement of lesions , since the low - density lung provides natural contrast for the dense pulmonary nodule , variability in the application of response criteria could compromise the reproducibility of results .\nmajor potential sources of response evaluation variation are imaging techniques , inter - observer variability , and the selection of target lesions [ 12 , 13 ] . in order to minimize observer variation ,\nthis study applied helical ct scanning and had the lesions measured by the same radiologist to evaluate response of the multiple metastases in the same patient , as routinely done in the clinical setting and in study protocols .\nthe presence of a new nodule was the main factor for determining disease progression , and the proportion of these new nodules in some cases was as low as 5% .\nthe systematic evaluation of all the patients nodules is then necessary to guarantee the identification of a new nodule .\nthe individual nodules in the same patient have individual and unpredictable behavior and can be evaluated as independent lesions . by using the who and the recist criteria of tumor response to therapy we verified that there were nodules labeled as disease progression in patients classified as stable , and unaltered nodules in patients evaluated as having progressive disease . in our patient population the proportion of nodules in a patient with response evaluation different from that obtained taking the sum of all nodules together amounted to 35% .\nthe results confirmed our previous impression that the application of the who or the recist method to one or some nodules in a patient , as frequently utilized by protocols , could also be misleading . in the same patient , one could select a stable nodule , a nodule with growth or a nodule in regression , and this could result in a decision error regarding the treatment regimen .\nthe use of the sum of the evaluation of all nodules together maximizes the reproducibility of response evaluations . in this study\nwe tried to reproduce what seem to be the usual conditions for tumor response evaluation in most protocols and institutions ; some of these conditions are limitations for the best possible response evaluation accuracy , but are close to clinical practice standard conditions .\nthere was no histological proof of the metastatic nature of the lung nodules , and some could have been infectious or inflammatory ; in clinical practice , however , histological proof is rarely required and the presence of new pulmonary nodules and overall oncologic disease progression are the criteria adopted by the oncologist for a diagnosis of lung metastases . when this study was conducted\nnowadays many institutions with faster and multiple detector cts adopt 5 mm or less in the evaluation of lung metastases .\nhowever , the recommendation of the authors of the recist group criteria was followed in measuring lesions no smaller than twice the size of the slice thickness .\nhard copy measurements were taken , despite having been shown to be less reproducible than computer display methods , as computer measurement is not always available , especially to the oncologist . in conclusion , there is a high correlation between the world health organization criteria and the recist group criteria .\nintra - individual variation in tumor response of pulmonary metastases is elevated in some patients , and chemotherapy response evaluation utilizing only one or some of the patient s nodules could lead to inappropriate reproducibility in therapeutic response perception .\nintra - individual distribution of response evaluation of pulmonary metastases by world health organization criteria . \nintra - individual distribution of response evaluation of pulmonary metastases by the response evaluation criteria in solid tumors ( recist ) group criteria . \ndistribution of primary types of metastatic solid tumor response evaluation of measurable nodules ( > 14 mm ) assessed by the who and the recist criteria response evaluation of patients assessed by the who and the recist criteria impact of the presence of new nodules in the patient s global response evaluation assessed by the recist criteria bold type indicates evaluations in which a new nodule was the sole criterion for disease progression .", "answer": "objective : with the introduction of cross - sectional imaging methods the number of lesions per patient that can be evaluated is frequently large and most oncologists and study protocols use only one lesion or a few representative lesions to evaluate chemotherapy response \n . intra - patient response variability can therefore affect evaluation reproducibility . \n this study evaluates intra - individual variation in response to chemotherapy in patients with multiple lung metastases . \n methods : we prospectively studied chest ct images of patients with solid tumors and pulmonary metastases under systemic chemotherapy being evaluated for tumor response . \n the response of 566 pulmonary nodules in 41 evaluations was determined by both who and recist criteria in order to determine intra - individual tumor response variation . \n results : there was almost perfect agreement between the who and the recist criteria for the evaluation of tumor response . \n high intra - individual variability of tumor response was observed in a significant proportion of the evaluations . \n a new nodule was the main criterion for determination of disease progression . \n a mean of 35% of the total number of nodules of a patient have a response evaluation different from that calculated with all the nodules together . \n conclusions : intra - individual variation in tumor response of pulmonary metastases is elevated in some patients . selecting any or some nodules for response evaluation could significantly influence therapeutic response perception .", "id": 58} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA straightforward approach towards combined \u03b1-amino and \u03b1-hydroxy acids based on Passerini reactions\n\nPaper sections:\nIntroduction\nMulticomponent reactions (MCR) are a very popular and powerful tool in modern organic synthesis [1][2][3][4]. Besides a wide range of heterocycle syntheses [5] and catalytic cross coupling reactions [6], the isonitrile-based MCRs (IMCR) especially have developed exceptionally well during the last few decades [7,8]. Based on the pioneering work of Passerini, who observed the first three-component coupling of carbonyls with carboxylic acids and isonitriles in 1921 [9], the so-called Passerini reaction became a powerful tool for the synthesis of acylated \u03b1-hydroxyacid amides [10]. Later on, in 1961, Ugi and Steinbr\u00fcckner reported the extension of this protocol by incorporating also a primary amine as a fourth component [11].
Therefore, the Ugi reaction is even more flexible than the Passerini approach, but both reactions together have made the IMCR highly popular in combinatorial chemistry [7,8].
Our group has been involved in amino acid and peptide synthesis for nearly two decades [12,13], and multicomponent reactions are known to play a dominant role [14,15]. In particular, the Ugi reaction has so far been used for the construction of exotic peptides [16][17][18][19] and cyclopeptides [20,21]. Herein we describe a straightforward protocol towards combined \u03b1-amino and \u03b1-hydroxy acids through Passerini reactions. Suitable amino acid precursors with an oxygen functionality in the side chain can be obtained by chelated enolate Claisen rearrangement [22,23] or transition metal-catalyzed allylic alkylation of chelated enolates [24] and subsequent oxidative cleavage of the \u03b3-\u03b4-unsaturated amino acids obtained.
\n\nResults and Discussion\nAn alternative approach is based on regioselective ring opening of epoxides, followed by oxidation of the hydroxy amino acid formed. While aryl-substituted epoxides react preferentially at the benzylic position giving rise to the terminal primary alcohols [25], the corresponding alkyl-substituted epoxides provide secondary alcohols 1 by nucleophilic attack of the enolate at the sterically least-hindered position [26]. These alcohols can easily be oxidized by Swern-oxidation [27] or with Dess-Martinperiodinane (DMP) [28], giving rise to the required \u03b3-oxoamino acids 2 (Table 1). In principle both protocols are suitable for oxidation, but in general the yields obtained were better with DMP (82-93%), while under Swern conditions the yields were in the range of 75 \u00b1 3%.
With these \u03b3-oxo-\u03b1-amino acids 2 in hand, we investigated the Passerini reactions under neat conditions with acetic acid as the (liquid) acidic component and isocyano acetates as the reactive component (Table 2). Interestingly, no reaction was observed Scheme 1: Passerini reactions of \u03b1,\u03b2-unsaturated aldehyde 5.
with the methyl-substituted oxo acid 2a (entry 1); only the starting material was recovered. For this reason, we switched to activated ketones bearing an electron-withdrawing group at the \u03b1-position. With the chlorinated ketone 2b the yield was 65% (entry 2), and similar results were obtained with a range of aryloxy-substituted derivatives 2c-2f (entries 3-7). The new stereogenic center was formed without significant selectivity.
To increase the synthetic potential of this protocol we also applied the Pd-catalyzed opening of a vinyl epoxide with our chelated enolate (Scheme 1) [29]. In this case an amino acid 4 with an allyl alcohol side chain was formed which could be oxidized to the \u03b1,\u03b2-unsaturated aldehyde 5. Although these types of aldehydes are critical candidates in Passerini and Ugi reactions [30], we were interested to see if we could also obtain unsaturated Passerini adducts by this procedure. Our first attempts in CH 3 OH and CH 2 Cl 2 were unsuccessful. While no reaction was observed in CH 2 Cl 2 , in CH 3 OH the only product (besides starting material) was the unsaturated acetal resulting from a nucleophilic attack of the solvent on the aldehyde group. Therefore, we decided to run the reaction also under neat conditions as reported for the \u03b3-oxo-amino acids. With acetic acid as the acidic component the yield of 6a was comparable to the previous examples. In principle, other acids such as benzoic acid or Cbz-protected glycine can be used as well. The lower yield obtained in these cases probably results from stirring problems under these solvent-free conditions.
To circumvent the problems caused by the \u03b1,\u03b2-unsaturated aldehyde, we hydrogenated 4 before oxidation to obtain the saturated aldehyde 7. And indeed, under our optimized reaction conditions the addition product 8 could be obtained in 80% yield (Scheme 2). In principle, Ugi reactions are also possible, as illustrated with the formation of 9, although the yield was significantly lower in this case and the products are formed as a 1:1 diastereomeric mixture.
\n\nConclusion\nIn conclusion, we showed that the ring opening of epoxides, either directly or Pd-catalyzed, with chelated enolates combined with Passerini reactions is a suitable tool for the synthesis of highly functionalized \u03b1-hydroxy and \u03b1-amino acid derivatives. These new compounds are interesting building blocks for peptide-derived drugs. Attempts to improve the yields and to evaluate the scope and limitations are currently underway.
\n\nSupporting Information\nSupporting Information features detailed experimental procedures, NMR as well as analytical data of all compounds.
Supporting Information File 1
Experimental section.
[http://www.beilstein-journals.org/bjoc/content/ supplementary/1860-5397-7-151-S1.pdf]
", "answer": "Complex amino acids with an \u03b1-acyloxycarbonyl functionality in the side chain are easily available through epoxide opening by chelated enolates and subsequent oxidation/Passerini reaction. This protocol works with both, aldehyde and ketone intermediates, as long as the ketones are activated by electron-withdrawing groups. In principle Ugi reactions are also possible, allowing the generation of diamino acid derivatives.", "id": 59} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nectopic thyroid tissue is a common abnormality and results from abnormal embryologic development and migration of the thyroid gland .\nsuch tissue is usually found along the path of descent of the thyroid gland in the anterior midline of the neck .\na lingual thyroid is the most common presentation of thyroid ectopy along with thyroglossal duct remnants . \nectopic thyroid tissue has been described in other parts of the head and neck such as the submandibular [ 3 , 4 ] and parotid salivary glands .\nthere are case descriptions of thyroid tissue identified in diverse locations such as the axilla , trachea [ 710 ] , adrenal , small intestine , and porta hepatis .\nthe most frequent noncervical location for ectopic thyroid tissue is the thoracic cavity [ 1418 ] .\n, the authors describe a case of ectopic anterosuperior mediastinal thyroid mass excised through a cervical incision and the subsequent investigation to exclude malignancy .\nan 80-year - old nonsmoker female patient presented with an incidental finding of a mediastinal mass on mri scan for investigation of vertigo ( figures 1 and 2 ) .\nthyroid stimulating hormone ( tsh ) and free thyroxine ( ft4 ) were within the normal range , and routine preoperative blood tests were normal .\nan anteroposterior chest radiograph demonstrated deviation of the intrathoracic trachea around the mass ( figure 3 ) . a subsequent ultrasound scan demonstrated a superior mediastinal mass separate from the inferior pole of the right thyroid lobe measuring 4.8 cm in maximal diameter ( figure 4 ) .\nthe first sample was inadequate ( thy1 ) , the second sample demonstrated only colloid and a few follicular cells .\nsince malignancy could not be definitively ruled out , the mass was excised through a cervical incision . under general anesthesia , the patient was placed in the supine position with the neck extended , prepared , and draped .\nendotracheal laryngeal nerve monitoring was used with nim contact emg endotracheal tube and nim - response 2.0 monitor ( medtronic usa , inc.6743 southpoint drive north , jacksonville , florida , usa , 32216 - 0980 ) . through a standard 5 cm midline cervical incision\n, the right thyroid lobe was dissected , found to be grossly normal , and excised .\nthe right recurrent laryngeal nerve was identified in the normal position , confirmed functioning with nerve stimulation at 2 ma , and preserved . \nseparate and inferior to the right thyroid lobe a discrete encapsulated mass was identified in the superior , mediastinum .\nthis extended across the anterior surface of the trachea to the left side , adjacent to the thymus .\nthe mass was separated from the thyroid gland by fat , in the same tissue plane but with no identifiable connection to the cervical region .\nthe mass was excised through the cervical incision . during excision of the mass , a double vascular pedicle , arising from inferiorly in the mediastinum ,\nhistopathologic evaluation of the excised mediastinal specimen demonstrated a 5.3 cm by 2 cm thyroid tissue mass with large oedematous loose areas and foci of calcification and fibrosis ( figure 5 ) .\nthe excised right thyroid lobe had a nodular architecture composed of follicles of varying sizes with focal lymphoid aggregates.thyroid function tests at 3 months were normal .\nfurther investigation with whole body radioiodine i123 scintigraphy demonstrated expected residual uptake in the remaining left thyroid lobe and surgical bed but no uptake suggestive of other ectopic thyroid tissue or metastatic disease .\nultrasound surveillance of a 9 mm nodule in the remaining left lobe demonstrated no change in size over 6 months .\nin humans , the thyroid gland begins to develop at the 24th day of gestation .\nthe thyroid is the first endocrine gland to develop and originates from between the first and second branchial arches .\nan invagination of endodermal epithelial cells begins at the midline of the developing pharyngeal floor forming a diverticulum .\nthis site , known as the foramen caecum , lies between the tuberculum impar ( median tongue bud ) and the hypobranchial eminence ( copula ) .\nthe foramen caecum can be observed in adults as a small pit at the base of the tongue where the tongue is divided into an oral anterior two - thirds and pharyngeal posterior third by the sulcus terminalis .\nthe initial path of descent of the bilobed thyroid diverticulum is anterior to the pharyngeal gut , the hyoid bone , and the laryngeal cartilages . at the same time\nembryological studies have shown that the strap muscles pull downward on the hyoid bone during development causing a forward tilt .\nthis tilt pulls the tract posteriorly and causes it to be hooked up behind the hyoid bone .\nthis explains the importance of excision of the median portion of the hyoid bone in the sistrunk procedure to excise a thyroglossal duct cyst . \nthe gland reaches its final location anterior to the trachea by the 7th week gestation . by this stage , it has acquired a median isthmus and two lateral lobes .\nas it descends , it is joined by the ultimobranchial bodies which form the parafollicular c cells .\nthyroid function begins at around the end of the 3rd month when the follicular cells commence production of colloid and follicles appear . during migration , from the 5th week gestation\n, the thyroid is still connected to the tongue by the thyroglossal duct . in normal development , this tubular structure subsequently obliterates entirely at approximately the 8 to 10th week . in some individuals , however , abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue .\nthese remnants can appear at any point along the migratory path and are always located at or near the midline .\nthe majority of remnants are found at , or just inferior to , the body of the hyoid bone as a thyroglossal cyst .\nremnants can also be found in the tongue base as a lingual thyroid or close to the thyroid cartilage .\nthe inferior end of the thyroglossal duct may fail to obliterate , and in at least half of individuals , a pyramidal lobe of the thyroid can be seen to persist .\nthis pyramidal lobe itself may be attached to the hyoid bone or may be incorporated into a thyroglossal duct cyst .\nectopic thyroid tissue in other locations is rare and generally the subject of single case reports .\nthe most important diagnosis to exclude is metastatic lymph node deposits of well - differentiated thyroid carcinoma .\nindeed , it is generally accepted that early reports of lateral aberrant thyroid tissue may represent papillary thyroid carcinoma metastases .\nanother hypothesis is that a thyroid nodule may become detached from the gland . in this case\n, the vascular supply should come from branches of the superior or inferior thyroid artery .\nthere are reports of thyroid deposits in the soft tissues of the neck representing surgical implantation of thyroid neoplasms . in one case ,\ninfiltrating thyroid tissue in muscle and fibrous tissue presented 3 years after major blunt trauma to the neck .\nthe tissue resembled that in a disrupted thyroid nodule present in the gland itself and was regarded as traumatically implanted .\nthere are , however , a number of ectopic thyroid masses reported which do not have features consistent with these theories and are considered truly developmental .\nanimal studies suggest that ectopic location of thyroid tissue may be related to vascular development .\nthe normal arterial supply of the thyroid gland consists of paired superior and inferior thyroid arteries . the superior thyroid artery is generally considered to be present in 100% of cases , and its absence has only been reported once . an unusually large superior thyroid artery may replace the contralateral vessels or the inferior thyroid artery .\nthe inferior thyroid artery when unusually small or absent may be replaced or supplemented by a thyroidea i m a artery .\npublished reports place the incidence of a thyroidea i m a artery between 2% and 12% . in the case\nthe ectopic mass was separate from the thyroid gland but in the same anatomical plane .\ncareful histological examination of the mass and the excised ipsilateral thyroid lobe demonstrated no evidence of neoplasia , and exhaustive investigations showed no evidence of thyroid malignancy elsewhere .\nthe authors therefore conclude that this represents developmentally ectopic sequestered thyroid tissue in the anterior mediastinum . despite this\n, the authors suggest that abnormally situated thyroid tissue , other than that in the central neck along the path of embryological descent of the thyroid gland , should be excised for careful histological analysis in order to exclude metastatic disease .", "answer": "an 80-year - old female presented with an incidental finding of a retrosternal mass on magnetic resonance imaging . \n ultrasound demonstrated a mediastinal lesion adjacent to but separate from the inferior pole of the right thyroid lobe . \n fine needle aspiration cytology demonstrated colloid and follicular cells . at surgery \n , the right thyroid lobe was found to be normal . \n a discrete 5 cm nodule was found in the anterior mediastinum separate from the thyroid and just anterior and to the right of the trachea and thymus . \n the nodule had a vascular pedicle arising from the mediastinum . \n the differential diagnosis included metastatic thyroid carcinoma . \n histology was consistent with a benign ectopic sequestered thyroid nodule . \n extensive investigations demonstrated no sign of a thyroid malignancy .", "id": 60} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey are present in 10 to 55% of cases trotter , konarik , reaching 23% of cases in the free part of the limb - valsecchi .\nthe brachial artery begins at the distal border of the tendon of the teres major muscle and ends close to the elbow joint .\nfrequently the brachial artery divides more proximally into radial , ulnar and common interosseous arteries .\nsome of the common variations of the brachial artery are present in the superficial brachial artery of the arm .\nthis artery moves together with the median nerve and continues as the radial artery twice as frequently , when compared to the ulnar artery ; less frequently it continues as both arteries - bergman et al . .\nthe brachial artery is used in routine procedures , such as blood pressure recordings and arteriography of different parts of the body .\nvariation in the proximal and distal branching pattern of brachial artery is important for vascular surgeons .\nthe superficial palmar arch is formed predominantly by the ulnar artery , with a contribution from the superficial palmar branch of the radial artery .\naccording to the classic description ( goss , bouchet & cuilleret , anastomosis among the ulnar and radiopalmar arteries form the superficial palmar arch .\nadachi thinks that the superficial palmar arch has an ulnar - predominant formation , which he calls the ulnar - type ( 59% of cases ) .\ncoleman & anson developed a classification , in which the superficial palmar arch is formed in 78.46% of cases .\nthe hand surgeon needs to know about the existence and healthy functioning of the palmar arch and the types of variations .\nthis is very important before surgical procedures such as arterial repairs or a vascular graft .\nthe main purpose of this case report is to describe the blood supply variations in the upper limb and to analyze the actual formation of the superficial palmar arch in the palm region .\nthe case was described after a routine dissection during the anatomy class with students from the department of anatomy , histology and pathology at the medical faculty of the university of sofia .\nthe 75 years old male cadaver was fixed with the formaldehyde method . at the left upper limb\nwere observed and documented vascular variations of the brachial artery and composition of the superficial artery arc .\nit became possible to trace the brachial artery after the removal of subcutaneous adipose tissue and venous branches .\nthis division was approximately at 10.4 cm from the beginning of brachial artery ( figure 1 ) .\nthis superficial brachial artery became radial and was not involved in the formation of the palm arch .\nthe superficial brachial artery pathway was closer to the median nerve in the first several centimeters , but after that it strayed on the lateral position and passed through the lateral sulcus of the cubital region . in this region , the brachial artery together with the ulnar and median nerve passes along the medial sulcus .\nthe brachial artery on the forearm gives the beginning of median , common interosseous and ulnar branches approximately 4 cm after the cubital region ( figure 2 ) .\nthe pathway of the median artery is accompanied by the median nerve and on the distal forearm part composes the superficial artery arch .\nthis structure is an anastomosis between the median and ulnar artery ( figure 3 ) .\nthe brachial artery persisted in the brachial region without the superficial branch and on the proximal forearm was divided by the common interosseous , ulnar and radial artery .\nthe superficial palmar arch was the connection between the ulnar and the radial artery in this case .\nat the time of embryo development , the deep artery system of the upper limbs originates from the primitive axial artery and superficial brachial artery ( muller , senior , rodriguez - baeza a , et al . ) .\nthe axillary , brachial and interosseous arteries are the main branches of the primitive axial artery .\nthe brachial and axillary arteries merge with the help of the superficial brachial artery in the proximal region of the arm .\ndistally , the superficial brachial artery anastomoses with the brachial artery by medial branch of the superficial brachial artery .\nthe derivatives of the forearm artery are median ( colligate with the deep branch of the radial artery , the branch of the primitive avail artery ) and the ulnar artery , which anastomoses with the terminal trunk of the primitive axial artery ( ulnar system ) .\naccording to singer , because of these anastomoses , there is an increase in the local blood flow and involution of the proximal segment of the superficial brachial artery . in this case\nit is possible for the ulnar artery to arise directly from the primitive axial artery .\nthis is one of the common morphological and genetic alterations found in the variations of the upper limb blood supply .\nchanges in the origin or involution of these segments are the cause of morphogenetic alterations found in the anatomy of the arteries of the upper limbs .\nthe position of the high bifurcation of the brachial artery relative to the biepicondylar line of the elbow and the pathway of median nerve are observed very well .\nmost significant research of detailed arterial variations of the upper limb are articles by adachi , bouchet & cuilleret coleman & anson ; according to these authors summative of more than a thousand cases , 18.5% are anatomical variations , 77% being cases with high origin of radial artery , while the ulnar artery was a persisting 12.2% of the variations .\ndescribed a case of arterial malformation in an old female cadaver , whereby the radial artery was formed in the axillary artery with a superficial path in an anterior region of the arm , converging deeply at the brachial artery in the cubital fossa . according to pelin et al . \nthe high origin of the radial artery is 14.27% in dissections of cadavers and 9.75% in an angiographic study . in some cases\ndescribed one case of triple branches of brachial artery on the 4.9 cm , which began at the brachial artery and formed the radial , ulnar and superior collateral ulnar arteries .\nanother interesting case described the trifurcation of the brachial artery occurring in the proximal third of the forearm and composing the radial , ulnar and common interosseous branches , which passed into the pronator teres muscle .\nthe presence of the superficial brachial artery originating in the axillary artery was observed in 12.2 % of 304 korean cadavers .\nthe superficial palmar arch ( spa ) is the main vascular structure of the palm region and is localized beneath the same name aponeurosis .\ncoleman ss , anson bj found a 37% chance occurrence of a complete arch , formed entirely by the ulnar artery .\nthey observed more than 650 specimens , while exploring the spa , and found out that the ulnar artery joined a large vessel from the deep palmar arch at the base of the thenar region .\nthe median artery ( ma ) of the antebrachial forearm region is the most important vessel at the time of embryo development .\nit maintains the superficial palmar arch ( spa ) , while the radial and ulnar arteries are developing .\nwhen the main arteries of this region are fully developed ( radial and ulnar arteries ) , the median artery disappears . in very rare cases ,\nafter that the ma may form the spa ( claassen h , schmitt o , wree a . due to its close proximity to the median , the median artery nerve can be involved in several clinical disorders such as carpal tunnel syndrome , anterior interosseous nerve syndrome and pronator syndrome . in view of the described variations\n, we believe that the knowledge of this unusual blood supply is extremely important , especially for the clinical or surgical practice .", "answer": "variations of arterial patterns in the upper limb have represented the most common subject of vascular anatomy . \n different types of artery branching pattern of the upper limb are very important for orthopedists in angiographic and microvascular surgical practice.the brachial artery ( ba ) is the most important vessel in the normal vascular anatomy of the upper limb . \n the classical pattern of the palmar hand region distribution shows the superficial palmar arch . \n normally this arch is formed by the superficial branch of the ulnar artery and completed on the lateral side by one of these arteries : the superficial palmar branch of the radial artery , the princeps pollicis artery , the superficial palmar branch of the radial artery or the median artery.after the routine dissection of the right upper limb of an adult male cadaver , we found a very rare variant of the superficial arch artery a division in a higher level brachial artery . \n we found this division at 10.4 cm from the beginning of the brachial artery . \n this superficial brachial artery became a radial artery and was not involved in the formation of the palm arch . in the forearm region , \n the artery variant was present with the median artery and the ulnar artery , which form the superficial palm arch .", "id": 61} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nadenomyosis is a common gynecological condition that is characterized by ingrowths of the endometrial cells into the myometrium .\nadenomyosis and leiomyoma are benign conditions that are often responsible for uterine enlargement , menorrhagia , anemia , and infertility .\nadenomyosis or internal endometriosis may occur as a result of increased overgrowth of the endometrium with invasion of the underlying myometrium or the displacement of the endometrium during pregnancy , delivery , endometrial curettage , cesarean section , myomectomy , or metroplasty .\nbecause of its similarities to leiomyoma , it can be difficult in some cases to accurately diagnose adenomyosis by ultrasound .\nmost gynecologists will consider conservative medical treatment more often for adenomyosis only , while surgical options will be chosen frequently for leiomyoma or combined adenomyosis and leiomyoma , especially in large uteri .\nthe three most common methods of clinical diagnosis of adenomyosis are magnetic resonance imaging ( mri ) , transabdominal ultrasonography ( tas ) , and transvaginal ultrasonography ( tvs ) .\nthere is limited diagnostic capacity with tas , while tvs is a more feasible option .\nmoreover , tvs is also much more cost effective than mri and is generally more readily available in the office to most practicing gynecologists .\nthe aim of this retrospective study was to determine the accuracy , sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of tvs in the diagnosis of adenomyosis and leiomyoma confirmed by postsurgical histopathological findings .\nthe importance of an accurate noninvasive diagnostic method like ultrasound for adenomyosis , leiomyoma , or combined is an ongoing need in the gynecological community .\nthis was an institutional review board ( irb ) approved retrospective consecutive case series study . from november 2006\nto may 2012 , patients underwent surgery for the treatment of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma .\ndiagnostic criteria of uterine adenomyosis include two of the five sonographic features on tvs : ( 1 ) no distinction of the endometrial - myometrial junction ; ( 2 ) asymmetry of the anterior and posterior myometrium ; ( 3 ) subendometrial myometrial striations ; ( 4 ) myometrial cysts and fibrosis ; and ( 5 ) heterogeneous myometrial echotexture . diagnostic criteria of uterine leiomyoma include two of the five sonographic features on tvs : ( 1 ) clear demarcation of the tumor margin ; ( 2 ) whorly appearance of the tumor content ; ( 3 ) the presence of blood vessels ( by color doppler ) surrounding the tumor ; ( 4 ) irregularities of the uterine surface ( subserous and intramural tumors ) ; and ( 5 ) irregularities of the endometrial surface ( submucous tumors type 1 and 2 ) .\nsymptomatic patients diagnosed with adenomyosis and leiomyoma via tvs underwent myomectomy with excision of the surrounding myometrium which presumably contained adenomyosis . following surgery , a histopathological examination was performed by the hospital pathologists .\nstudent 's t - tests were used for parametric continuous variables ; and the chi - square or fisher 's exact test , where suitable , was used for categorical variables .\nsensitivity , specificity , npv , ppv , positive and negative likelihood ratios , and accuracy were determined for ultrasound findings as they corresponded to the final histopathological diagnosis .\nfrom november 2006 to may 2012 , 163 patients underwent surgery for the treatment of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma .\none hundred and twenty - three patients were diagnosed with adenomyosis , and 134 patients were diagnosed with leiomyoma .\ntwenty - nine patients were diagnosed with adenomyosis only , 40 patients were diagnosed with leiomyoma only , and 94 patients were diagnosed with combined adenomyosis and leiomyoma , as illustrated in figure 1 .\npatient diagnosis groups one hundred and thirty patients diagnosed with adenomyosis or combined adenomyosis and leiomyoma via tvs underwent hysterectomy .\nthe mean age was 43.7 years with a standard deviation ( sd ) of 6.7 years and median of 43 years .\nthere was no significant difference in the mean age , weight , height , gravidity , and parity of the patient diagnosis groups .\npatient characteristics for 163 females who underwent hysterectomy or myomectomy between 2006 and 2012 of the 123 patients ( 75.46% ) who were positively diagnosed with adenomyosis , 93 of the patients ( 75.61% ppv ) diagnoses were confirmed by the histopathological findings .\nhistopathological reports found 23 ( 57.50% npv ) confirmed negative diagnoses and 17 ( 42.50% ) positive findings .\nthe sensitivity of tvs in the diagnosis of adenomyosis was 84.55% ( 95% ci 76.4 - 90.7 , p < 0.0001 ) and the specificity was 43.40% ( 95% ci 29.8 - 57.7 , p = 0.41 ) .\ntable 2 shows the sensitivities , specificities , ppvs , npvs , and accuracy for each of the initial tvs diagnoses .\nthis could be explained by the difficulty to diagnose adenomyosis in patients with other intrauterine abnormalities or conditions .\npatients positively diagnosed with adenomyosis via tvs are 1.49 ( 95% ci 1.16 - 1.92 , p < 0.002 ) times more likely to have the condition .\nconversely , patients negatively diagnosed with adenomyosis via tvs are 2.81 ( 95% ci 1.65 - 4.79 , p = 0.0002 ) times less likely to have the condition .\nnumber of patients , positive and negative predictive values , sensitivity , specificity , and accuracy of transvaginal ultrasound for initial diagnosis with histopathological correlation ( n=107 ) one hundred and thirty - four patients ( 82.21% ) were diagnosed with leiomyoma and 29 patients ( 17.79% ) were negative for leiomyoma upon the initial tvs .\nof the 134 patients diagnosed with leiomyoma , 133 ( 99.25% ppv ) had a confirmed diagnosis represented in their postsurgical pathology report and one patient 's ( 0.75% ) pathology report did not confirm the diagnosis .\nof the 29 patients whose tvs diagnosis was negative for leiomyoma , 24 ( 82.76% ) patients histopathological findings were also negative , and five patients ( 17.24% ) had a positive histopathological diagnosis .\nthe corresponding sensitivity and specificity of tvs as a diagnostic test for leiomyoma was 96.38% ( 95% ci 91.75 - 98.81 ) and 96.00% ( 95% ci 79.65 - 99.90 ) , respectively .\npatients with a positive diagnosis of leiomyoma via tvs are 24.09 times ( 95% ci 35.30 - 164.45 , p = 0.001 ) more likely to have leiomyoma .\npatients with a negative diagnosis of leiomyoma via tvs are 26.53 times ( 95% ci 11.16 - 62.89 , p < 0.0001 ) less likely to have leiomyoma .\nfor the statistical calculations of adenomyosis and leiomyoma as coexisting conditions , analyses were performed excluding the patients who were diagnosed with a singular condition .\nthese patients were classified as negative solely for the purpose of calculations regarding the combined condition . of the 94 patients ( 57.67% ) that were positively diagnosed with combined adenomyosis and leiomyoma ,\n70 ( 74.47% ppv ) had histopathological confirmation of both conditions and 24 patients ( 25.53% ) did not have evidence of both conditions in their post - surgical pathology report .\nsixty - nine ( 42.33% ) patients had a negative tvs diagnosis for combined adenomyosis and leiomyoma , and 49 ( 71.01% npv ) had histopathological confirmation of the negative diagnosis . however , 20 patients ( 28.99% ) had a positive histopathological diagnosis for both adenomyosis and leiomyoma . the sensitivity and specificity of tvs in the diagnosis of combined adenomyosis and leiomyoma was 77.78 ( 95% ci 67.79 - 85.87 ) and 67.12% ( 95% ci 55.13 - 77.67 ) , respectively .\npatients who obtained a positive tvs diagnosis are 2.37 times ( 95% ci 1.67 - 3.34 , p < 0.0001 ) more likely to be diagnosed with combined adenomyosis and leiomyoma .\nalternatively , patients who are negatively diagnosed with adenomyosis and leiomyoma via tvs are 3.02 times ( 95% ci 1.99 - 4.59 , p < 0.0001 ) less likely to be diagnosed with combined adenomyosis and leiomyoma .\nadenomyosis is a gynecological disorder that is characterized by the overgrowth of the endometrium into the underlying myometrium .\nthe difficulty in diagnosing adenomyosis clinically is due to the lack of strong positive pathognomonic signs and/or clinical findings .\nthe explanation for this wide range of values , as described by azziz , is the result of differences in the histological criteria for the diagnosis of adenomyosis , the care of which the pathologic specimens are handled , and the number of blocks of sampling specimens taken .\nvarious measures of accuracy were calculated for the diagnosis of adenomyosis , leiomyoma , and combined adenomyosis and leiomyoma .\ntable 3 shows a comparison of sensitivity , specificity , ppv , and npv of this study with several previous studies that investigated the diagnosis of adenomyosis .\nit is important to note that the mean number of patients included in the 13 previous studies in table 3 is 76.8 patients ; however , this study utilized 163 patients in the analyses .\nalong with differences in inclusion criteria , ultrasound equipment , and/or the differences in the criteria to diagnose adenomyosis , the larger sample size could contribute to the difference in results .\nthe sensitivity and specificity of tvs for the diagnosis of adenomyosis in this study was 84.55 and 43.40% , respectively .\nthe associated p value for the specificity was not significant , suggesting tvs as a diagnostic tool is sensitive , but not specific in the diagnosis of adenomyosis .\nthe sensitivity in this study is similar to those previously reported in table 3 , but the specificity is the lowest of those reported .\nthis could be due to the difficulty in diagnosing adenomyosis in the presence of other uterine abnormalities and conditions , especially uterine leiomyomata that may distort the uterus .\npatients that were diagnosed with multiple intrauterine conditions were not excluded from this study , since the principle inclusion criteria was patients who underwent hysterectomy or myomectomy and a preoperative tvs .\nsensitivity , specificity , positive and negative predictive values of tvs for the diagnosis of adenomyosis from previous series compared with this series the sensitivity of tvs for the diagnosis of leiomyoma was 96.38% and the specificity was 96.00% , which is similar to that of a previous study .\nthe sensitivity for the diagnosis of combined adenomyosis and leiomyoma was 77.78% , and the specificity was 67.12% .\nit was accurate , sensitive , and specific in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma .\ntvs was both accurate and sensitive in the diagnosis of adenomyosis , but not specific .\nmoreover , tvs is cost effective and readily available in the office to the majority of practicing gynecologists .\nthis study demonstrated that tvs is a valuable noninvasive method that should be utilized in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma .", "answer": "objective : to evaluate the accuracy , sensitivity , specificity , positive predictive value ( ppv ) , and negative predictive value ( npv ) of the diagnosis of adenomyosis , leiomyoma , or combined adenomyosis and leiomyoma by the use of transvaginal ultrasonography ( tvs ) compared to the histopathological findings.subjects and methods : this is a retrospective study of patients with a preoperative tvs diagnosis of adenomyosis , leiomyoma , or combined . \n patients diagnosed with adenomyosis or combined adenomyosis and leiomyoma via tvs underwent hysterectomy . \n symptomatic patients diagnosed with adenomyosis and leiomyoma via tvs underwent myomectomy with excision of the surrounding myometrium which contained possible adenomyosis . following surgery , a histopathological examination was performed by the hospital pathologists . \n the microscopic diagnosis of the specimen was recorded.results:tvs diagnosis of adenomyosis was sensitive but not specific . \n tvs was sensitive , specific , and accurate in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma.conclusion:this study demonstrated that tvs is a valuable noninvasive method that should be utilized in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma . \n tvs is sensitive , but is not specific in the diagnosis of adenomyosis only .", "id": 62} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsystemic thrombolytic therapy with recombinant tissue plasminogen activator ( rt - pa ) , intra - arterial thrombolytic therapy , and mechanical revascularization are therapeutic options in acute ischemic stroke ( ais ) in adults [ 1 , 2 , 3 ] . published experience in ais in childhood\na previously healthy 14-year - old boy was admitted with acute onset of severe left hemiparesis with a national institute of health stroke scale ( nihss ) score of 12 .\nthere was no prior history of trauma , infection or family history of migraine or other cerebrovascular disease , but the boy was complaining of frontal headache over the last 2 weeks .\nintravenous rt - pa infusion ( 0.9 mg / kg ) was started 3 h after onset of symptoms but was discontinued after 2/3 of dosage because of serious neurological deterioration .\nwe immediately performed an mri which revealed acute ischemic lesions in both territories of the anterior cerebral arteries ( aca ) and the left middle cerebral artery ( mca ) .\nmr angiography ( mra ) showed the right aca without flow signal , the left internal carotid artery ( ica ) with an intracranial stenosis , and several mca branches with lack of flow ( fig .\nseveral differential diagnoses were considered : dissection , isolated cerebral vasculitis , arterial spasms , infection , multiple cardiac embolism , and intoxication .\nscreening for heroin , amphetamine , ecstasy , ethanol , and cocaine in blood and urine was negative .\na previously healthy 10-year - old boy was admitted with acute severe left hemiparesis ( nihss 16 ) and headache after jumping on a trampoline .\nthere was no history of infection or family history of migraine or other cerebrovascular disease .\nmri revealed an acute ischemic lesion in the right mca territory , occlusion of the right ica , and a thrombus in the right mca ( fig .\n2 ) . intravenous rt - pa infusion ( 0.9 mg / kg ) was started within 3 h after onset of symptoms .\nas no improvement was observed at the end of the rt - pa infusion , mechanical revascularization was performed .\na goose neck snare was passed through the thrombus which was partially fragmented and finally dissolved .\nflow was established in the right mca and the branches 5 h after the onset of stroke ( fig .\nthe potential trauma ( bouncing trampoline ) and thrombus formation in the ica made an intima dissection most likely , but could not be confirmed by angiography . no stent was used and platelet inhibition was started the next day .\ntransesophageal echocardiography and routine blood samples , including extensive coagulation tests , were all normal .\nthe boy improved ( nihss 13 the next day ) and was transferred to the department of pediatric neurorehabilitation on day 3 . at 3 month\n, he was back to school , but was still suffering a slight hemiparesis ( modified rankin scale ( mrs ) 2 ) .\na previously healthy 14-year - old boy was admitted with acute onset of severe left hemiparesis with a national institute of health stroke scale ( nihss ) score of 12 .\nthere was no prior history of trauma , infection or family history of migraine or other cerebrovascular disease , but the boy was complaining of frontal headache over the last 2 weeks .\nintravenous rt - pa infusion ( 0.9 mg / kg ) was started 3 h after onset of symptoms but was discontinued after 2/3 of dosage because of serious neurological deterioration .\nwe immediately performed an mri which revealed acute ischemic lesions in both territories of the anterior cerebral arteries ( aca ) and the left middle cerebral artery ( mca ) .\nmr angiography ( mra ) showed the right aca without flow signal , the left internal carotid artery ( ica ) with an intracranial stenosis , and several mca branches with lack of flow ( fig .\nseveral differential diagnoses were considered : dissection , isolated cerebral vasculitis , arterial spasms , infection , multiple cardiac embolism , and intoxication .\nscreening for heroin , amphetamine , ecstasy , ethanol , and cocaine in blood and urine was negative .\na previously healthy 10-year - old boy was admitted with acute severe left hemiparesis ( nihss 16 ) and headache after jumping on a trampoline .\nthere was no history of infection or family history of migraine or other cerebrovascular disease .\nmri revealed an acute ischemic lesion in the right mca territory , occlusion of the right ica , and a thrombus in the right mca ( fig .\n2 ) . intravenous rt - pa infusion ( 0.9 mg / kg ) was started within 3 h after onset of symptoms . as no improvement\nwas observed at the end of the rt - pa infusion , mechanical revascularization was performed .\na goose neck snare was passed through the thrombus which was partially fragmented and finally dissolved .\nflow was established in the right mca and the branches 5 h after the onset of stroke ( fig .\nthe potential trauma ( bouncing trampoline ) and thrombus formation in the ica made an intima dissection most likely , but could not be confirmed by angiography .\ntransesophageal echocardiography and routine blood samples , including extensive coagulation tests , were all normal .\nthe boy improved ( nihss 13 the next day ) and was transferred to the department of pediatric neurorehabilitation on day 3 . at 3 month\n, he was back to school , but was still suffering a slight hemiparesis ( modified rankin scale ( mrs ) 2 ) .\nthe current american heart association pediatric stroke guidelines advocate thrombolytic therapy for childhood ais only in the setting of clinical trials .\nin contrast , the european stroke organization guidelines suggest that intravenous rt - pa may be administered in selected patients under the age of 18 beyond the current european recommendations . experience with systemic thrombolytic therapy and intra - arterial revascularization in ais in children is limited . the nationwide inpatient sample in the us recorded data of 2,904 children with stroke .\n( 687 children ) , 2% of children received thrombolytic therapy , 9% received intravenous and 6% intra - arterial therapy .\nboth studies showed increased in - hospital mortality and worse outcome in children treated with thrombolytic therapy compared to conservative treatment , probably reflecting a treatment selection bias towards more severe stroke . furthermore , the thrombolytic therapy often deviated from the current adult stroke guidelines by delayed initiation .\nin contrast , a review of 17 cases published in the literature , which were treated with systemic thrombolytic therapy or intra - arterial revascularization , probably reflects a publication bias towards positive results with good outcome and low mortality .\nour two children were treated according to the stroke treatment guidelines for adults , and no rt - pa related intracranial hemorrhage or other side effects were seen .\nlower concentration of tissue plasminogen activator and higher concentration of plasminogen activator inhibitor type 1 in children might influence the dose - response relation of rt - pa .\nsystemic thrombolytic therapy is approved in ais in adults , in whom atherothrombosis is the most frequent cause of ischemic stroke .\nin contrast , in children , cardiac disease , prothrombotic or hematologic disorders , dissection , moyamoya disease and vasculitis are common etiologies . however , our children were both previously healthy .\nin the first case , endovascular therapy was not available in our center at that time .\nthe history of headache over the last 2 weeks was suspicious for vasculitis , but now signs of inflammation were found and the later organ transplantations caused no systemic vasculitis .\nthere were no other medical conditions that might have indicated that the changes on mra were associated with the moyamoya syndrome .\nanother consideration was arterial spasm due to intoxication , but the screening for toxins was negative .\nautopsy was not permitted by the parents , and the stroke etiology remained unclear . in the second case ,\nthe history of a potential trauma and thrombus formation in the distal ica made an intima dissection most likely , but could not be confirmed on angiography or mri after successful mechanical revascularization .\nthe clinical outcome after 3 month was good ( mrs 2 ) and full recovery was seen after 5 month . in conclusion ,\ntreatment of ais in childhood without being part of a randomized controlled trial needs a careful individual approach .\ndifferences in the fibrinolytic system and the different etiology of ais in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy .\nacute multimodal imaging with mra , ct angiography , or angiography to clarify the etiology of ais might help to select the most appropriate treatment modality .", "answer": "thrombolytic therapy is not recommended for acute ischemic stroke ( ais ) in patients under the age of 18 and published experience is limited . in this case report , we describe two children treated with systemic thrombolytic therapy . \n one child received additional mechanical revascularization and achieved a good clinical outcome . \n the differences in the fibrinolytic system and the different etiology of ais in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy . \n acute multimodal imaging to clarify the etiology of ais might help to select the most appropriate treatment modality .", "id": 63} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsuccessful outcomes of endodontic treatment depend on the identification of all roots and root canals which in turn guarantees complete extirpation of pulp tissue , proper chemomechanical cleaning and shaping and three - dimensional obturation of the root canal system with an inert filling material .\nfailure of at least one of these stages entails high risk of unsuccessful root canal treatment of the tooth with a subsequent development or persistence of a periapical lesion . normally , mandibular first molars have one mesial root and one distally .\nthe mesial root has two canals ( mesiobuccal and mesiolingual ) , ending mainly in two distinct apical foramina .\nthe distal root typically has one root canal , although if the orifice is particularly narrow and round , a second distal canal may be present .\nanatomical variations in the number of roots as well as canal configuration in mandibular molars are not uncommon [ 3 , 4 ] .\none of the major anatomical variations is the presence of an additional third root , also called the radix entomolaris ( re ) which is located distolingually in mandibular molars . in very rare cases , when this additional root is located mesiobuccally , it is called radix paramolaris [ 5 , 6 ] .\nanatomical studies have reported an association between the presence of a separate re in the first mandibular molar and certain ethnic groups . in populations with mongoloid traits , such as chinese , eskimos , and american - indians ,\nit occurs with a frequency of 5 to more than 30% [ 7 , 8 ] . in african population ,\na maximum frequency of 3% was found [ 9 , 10 ] , whereas in europeans the incidence was even less .\nusing full - mouth periapical radiographs , investigated the incidence of radix entomolaris in german population .\nseven patients were found to have a three - rooted mandibular first molar with an overall incidence of 1.35% . in indian population , garg et al . examined 1054 periapical radiographs and reported 5.97% of occurrence of re in mandibular first molars .\nthe same method was used by karale et al . who reported a higher incidence ( 6.67% ) of re .\nknowledge of occurrence , location , and incidence of any tooth anatomical variation is important as it has a significant role in clinical dentistry .\nmany epidemiological studies have highlighted the importance of watching re while performing root canal treatment on mandibular first molars .\ndental schools have been very recently established in palestine and there is no single research dealing with teeth anatomy and the incidence of anatomical variation in our country . with a huge number of dentists and very few specialists in endodontics ,\nthis research has been conducted so as to provide information about various anatomical variations that could be encountered during endodontic therapy .\nthe purpose of this study was to evaluate the percentage of permanent mandibular first molar teeth with three roots in a palestinian population using conventional digital x - rays in two different angles .\nthree hundred and twenty two mandibular first molars from 185 females and 137 males of different ages scheduled for root canal treatment at the dental center of the arab american university were included in this clinical investigation .\nthe study sample represents all patients who needed primary root canal treatment or referred for retreatment over a 2-year period .\nthe age of the 322 participants ranged from 11 to 62 ( mean = 37 ) years .\nthis study was approved by the ethics committee of the school of dentistry research centre .\nthe criteria used to indicate the presence of re were clear distinction of an extra root , indicated by the crossing of translucent lines defining the pulp space and periodontal ligaments , originating in the upper half of the distal root .\none endodontist and one paediatric dentist ( both instructors of undergraduate dental students ) served as examiners in this study .\ndisagreement in the interpretation of the radiographs was discussed between the two investigators until a consensus was reached .\nat least two preoperative radiographs were taken for each tooth undergoing root canal treatment using a digital x - ray sensor ( dr . suni , san jose , california , usa ) .\none radiograph was taken from orthoradial position and the other taken either 30 mesially or distally . when the radiographs revealed a case of re , another radiograph for the opposing side was taken .\nafter obtaining adequate anaesthesia , the tooth was isolated with rubber dam and root canal treatment was initiated .\nthe pulp chamber was irrigated with 3% sodium hypochlorite and carefully examined with an endodontic probe ( dg-16 , dentsply , gloucester , uk ) .\nall canals were scouted using k - file number 10 ( dentsply , maillefer , ballaigues , switzerland ) .\nworking length was estimated using an apex locator ( novapex , forum technologies , rishon le - zion , israel ) and confirmed with a working length radiograph with k - files introduced into the canals .\nah plus ( dentsply detrey , konstanz , germany ) was used as a sealer .\na postoperative radiograph was taken to assess the technical quality of root canal filling . when satisfactory , a permanent filling was placed .\nfigures 1 , 2 , and 3 show an example of a mandibular first molar with three roots . the incidence of re and comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded .\ncomparison of the incidence and the correlations between males and females and left- and right - side occurrences were analyzed by using the pearson chi - square test with spss ( 15.0 ; spss inc . ,\nthree hundred and twenty two patients comprising 185 females and 137 males formed the study sample .\nthere was no significant difference in the incidence of three - rooted mandibular first molars between females ( 7/185 ) and males ( 5/137 ) ( table 1 ) .\nhowever , there was a significant difference between the right side ( 8/12 ) and the left side ( 4/12 ) ( p < 0.05 ) .\nknowledge of both normal and abnormal anatomy of teeth dictates the parameters for execution of root canal therapy and can directly affect the probability of success .\ntherefore , practitioners should be familiar with the existence as well as the prevalence of teeth abnormalities .\nmandibular first molars seem to be the most frequent teeth in need of root canal treatment as they are the first permanent teeth to erupt . nonetheless , anatomical variations of the root canal system in molars are not appreciated by a great number of general practitioners .\nthe presence of a third root ( re ) may complicate the endodontic treatment and lead to failure as a result of canal missing .\nwhile conducting root canal treatment in mandibular first molars , clinicians should be aware of this morphological abnormality . de moor et al . \ntype ii refers to an initially curved entrance which continues as a straight root / root canal .\ntype iii refers to an initial curve in the coronal third of the root canal and a second curve beginning in the middle and continuing to the apical third .\nthe infrequent occurrence of re requires that the clinician be cautious in diagnosis and management of the lower molar teeth .\nalthough it is not necessary , an additional root is often associated with an increased number of cusps and an increased number of root canals with a more prominent occlusodistal or distolingual lobe .\nradiographs taken at different angulations reveal the basic information regarding the anatomy of a tooth and can thus help to detect any aberrant anatomy such as extra canals and/or roots .\nwhen the outline of the distal root or the root canal seems unclear on the preoperative radiograph , the presence of a hidden third root should be suspected .\nstudies have shown that a second radiograph should be taken from a more mesial or distal angle ( 30 degrees ) which could probably reveal the presence of re .\nperiapical radiographs were used in this study because they are routinely used in the dental school of the arab american university throughout endodontic steps .\nthis technique is noninvasive and inexpensive and allows for interstudy comparisons relating to gender and bilateral occurrence difference for three - rooted mandibular first molars . on the other hand , this method has some disadvantages .\nas radix entomolaris is mostly situated in the same buccolingual plane as the distobuccal root , a superimposition of both roots can appear on the radiograph resulting in an inaccurate diagnosis .\nthe digital system offers many advantages over the conventional radiography such as ease and speed of use , reduction in time between exposure and image interpretation , less radiation dosage to the patient , elimination of chemical waste hazard , and the ability to digitally manipulate the captured image .\nunfortunately , a more advanced technology represented by the cone beam computed tomography ( cbct ) is not available .\ncone beam computed tomography scans were recently shown to be a valuable tool in several stages of endodontic treatment as they provide an immediate and accurate three - dimensional radiographic image .\npreoperatively , these images give information about the internal and external tooth anatomy which include number and location of roots and canals , root and canal curvatures , size of the pulp chamber , and the degree of calcification .\ncbct images allow a complete elimination of the superimposition of structural images outside the area of interest and provide a high - contrast resolution and data from a single computed tomography imaging process .\nthey also provide three dimensional images in the axial , coronal , or sagittal planes . in cases of re\n, cbct shows the exact position of distolingual root and hence it helps in tracking the curvature and prevents iatrogenic event that might occur in relation to canal curvature like instrument separation , perforation , ledge formation , and so forth .\nwhen the occurrence of re is confirmed or suspected on the radiograph , the access cavity preparation should be modified from the classic triangular access to a more rectangular or trapezoidal outline .\nthe orifice of re is mainly located disto- to mesiolingually from the main distal canal .\nif the entrance of re canal is not clearly visible after removal of the pulp chamber roof , a more thorough inspection of the pulp chamber floor and wall , especially in the distolingual region , is necessary .\nthe introduction of dental operating microscope ( dom ) has changed the face of endodontics . although the operating microscope is not used in our clinics , its use is recommended in routine endodontic practice as it offers an excellent illumination and magnification of the operating field and provides a tremendous advantage in locating and treating extra canals .\ncoelho de carvalho and zuolo reported that the dom had enabled them to locate 8% more canals in mandibular molars .\nal - nazhan has examined 251 mandibular first molars of saudi patients ( clinically and radiographically ) .\nhe reported an incidence of 6% of re amongst saudi population . in their clinical investigation conducted on chinese population , yu et al .\nscreened 378 cases of mandibular first molars with root canal therapy and reported an incidence of 27% of teeth with re . in our study\n, the overall incidence of patients with three - rooted mandibular first molars was 3.73% .\nthis finding was in a range of previous reports on middle easterners [ 24 , 26 ] .\nhowever , it was low when compared with data reported for asian races : 24.5% in koreans , 32% in chinese , and 25.6% in taiwanese . in the present study ,\nthe same result was reported by other studies [ 11 , 12 , 28 , 30 ] . when considering the right and left sides of the mandible\n, three - rooted mandibular first molars occurred more frequently on the right side than on the left side .\nthese findings were in accordance with some previous studies [ 12 , 28 ] and different from some others [ 11 , 31 ] which reported that re can occur more on the left side .\nloh report a bilateral occurrence of three rooted mandibular permanent first molars from 50 to 67% ; however , in our study the bilateral occurrence was only 33.3% .\nthis percentage was higher than the study on german population and much lower than the studies [ 2729 ] involving asian subjects ( koreans , chinese , and taiwanese , resp . ) .\ngeneral practitioners as well as specialists in endodontics should always think about a possible third root ( re ) when planning a root canal treatment for a mandibular first molar .\ncareful clinical and radiographic examination is indispensable in the diagnosis of any anatomic variation in the root canal system of any tooth prior to initiating treatment .\nas this study revealed that the incidence of a third root in palestinian population was within the range of previous reports from the middle east but considerably lower than the percentage from the far east , the use of conventional two - dimensional radiographs for the assessment of re would be probably considered as a limitation in the clinical approach and methodology of this study .\nhopefully , future research in palestine would be able to study a larger and more varied population utilizing cone beam computed tomography .", "answer": "purpose . \n the aim of this investigation was to evaluate clinically the percentage of permanent mandibular first molar teeth with three roots amongst palestinian population . \n patients and methods . \n three hundred twenty - two mandibular first molars from 185 females and 137 males scheduled for root canal treatment at the dental center of the arab american university were examined over a 2-year period . \n the incidence of a third root revealed by periapical radiographs and the comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded . statistical analysis . \n it was performed using the chi - square test with a significant level set at p < 0.05% . \n results . of the \n 322 treated mandibular first molars , twelve teeth were found to have a third root with an overall incidence being 3.73% . \n more teeth with a third root were treated on the right side of the mandible compared to the left side . conclusion . \n the incidence of a third root in palestinian population was within the range of previous reports from the middle east but considerably lower than the percentage from the far east .", "id": 64} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npositron emission tomography - computed tomography is useful for diagnosing primary and metastatic lesions of esophageal cancer .\nthe sensitivity and specificity of a pet / ct are also relatively preferable to other diagnostic imaging tools .\nalthough the number of cases is few , false positives exist in which an inflammatory tumor mass and a nonspecific tumor mass are difficult to differentiate between , even when combined with other image findings . in cases of esophageal cancer ,\nthe types of treatment and their prognosis are greatly affected if there is a metastasis or recurrence .\npositron emission tomography - computed tomographic false positives can not simply be ignored even if they appear to be due to inflammation or some other factors .\nthis case report discusses the reasons to conduct a pet / ct test and its limitations in diagnosing esophageal cancer .\nthe subjects of this investigation had suspected metastasis from a pet / ct which occurred before surgery of the 129 resected cases of esophageal cancer at our department from june 2010 to march 2015 .\nhowever , after surgery , biopsy and/or follow - up observation , only the cases that were confirmed as metastasis negative were considered to be pet / ct false positives for this assessment .\nthere were 3 cases of preoperative pet / ct false positives ( table 1 ) .\ntwo cases in which bone metastasis was suspected revealed almost normal range of squamous cell carcinoma ( scc)associated antigen , alkaline phosphatase , and serum calcium levels .\nabbreviations : ln , lymph node ; m , metastasis ; mt , middle thoracic lesion of esophagus ; n , node ; t , tumor ; ut , upper thoracic lesion of esophagus . in case 1 , a 59-year - old man , without particular medical history , had a diagnosis of esophageal carcinoma by endoscopy .\nmultiple bone metastases were suspected by a pet / ct in the spine , sternum , ribs , and pelvic bone ( figure 1 ) . after conducting a ct - guided biopsy of the right iliac bone ,\nthe patient is alive with no recurrence 4 years and 10 months after surgery , although the false - positive lesions in pelvic bone are still detected by pet / ct . in the case 1\n, multiple bone metastases were suspected by a positron emission tomography - computed tomography in the pelvic bone ( suvmax = 2.94 ) . in case 2 , a 71 year - old man , without particular medical history ,\nabnormal accumulations of fluorodeoxyglucose ( fdg ) in the manubrium sterni , vertebra th5 , and the pedicle of vertebral arch were found by pet / ct .\ntherefore , after the sufficient informed consent , the patient underwent a laryngopharyngeal esophagectomy , a transhiatal esophagectomy without thoracotomy , and reconstruction with the gastric tube through the posterior mediastinal route .\npathological finding showed poorly differentiated scc of esophagus and moderately differentiated scc of hypopharynx with a cervical lymph node metastasis .\nthe patient is alive with no recurrence 3 years and 11 months after the surgery . in case 3 ,\na 76-year - old man , without particular medical history , had a diagnosis of a superficial esophageal cancer by endoscopy .\nhe was suspected of lymph node metastasis of right recurrent nerve lymph node ( figure 2 ) by preoperative pet / ct .\n. scattered silicotic nodules and inflammatory lymphadenopathy might be caused by pneumoconiosis ( figure 3 ) .\ncase 3 was suspected of right recurrent nerve lymph node metastasis by preoperative positron emission tomography - computed tomography ( suvmax = 3.00 ) .\npathological finding of case 3 revealed scattered silicotic nodules in resected lymph nodes with infiltration of histiocytosis to sinusoid .\nin esophageal cancer treatment , fdg - pet / ct is also used to diagnose metastases and to judge the effectiveness of treatment . especially , pretherapeutic\nthere are cases when the surgery may not apply to a patient if remote metastasis or high - grade lymph node metastasis is found .\nmany cases have already been reported claiming that fdg - pet is a useful modality for a pretherapeutic staging .\nesophageal cancer causes 30% to 40% of lymph node metastases among cancers that spread to the submucosa , and the prognosis of esophageal cancer is known to be defined by the presence of lymph node metastasis , how many metastases are present , and how much the metastasis spreads .\ntherefore , evaluating lymph node metastasis is a very important factor in deciding the course of treatment .\nthe diagnosability of lymph node metastasis using a fdg - pet for esophageal cancer is generally reported to have a sensitivity of 32% to 51.9% , a specificity of 94.2% to 100% , and an accuracy of 48% to 93% .\nin addition , fdg - pet / ct , which is a combination of a fdg - pet and a ct , improves the diagnosability even more .\nyuan et al have reported that they evaluated the diagnosability of lymph node metastasis using fdg - pet / ct for esophageal squamous cancer and found a sensitivity of 94% , a specificity of 92% , and an accuracy of 92% . however , the size of a lymph node that can be detected by pet / ct is said to be only 6 to 8 mm , thus it is difficult to detect micrometastasis .\nalso , detecting metastasis to neighboring lymph nodes could be difficult in cases with a lot of fdg accumulation in the primary lesion , or accumulation in the intestinal tract such as in the stomach , or in the heart .\nthe fdg accumulates in inflamed lymph nodes as well , so false positives often appear in hilar lymph nodes or in patients who have chronic lung disease .\nlymph node metastasis was suspected after a preoperative pet / ct for the case 3 , as described above , but it was actually an inflammatory lymphadenopathy caused by pneumoconiosis .\ndual - time - point fdg - pet has been reported to be useful in reducing this kind of false positive .\nit uses the time differences of peak fdg accumulation for inflammation versus for tumors . after injecting the fdg ,\npet has revealed occult distant metastases at nodal and non - nodal sites in 5% to 40% of patients .\ndistant metastases of esophageal squamous cancer are mainly found in the lungs , liver , and bones .\nkato et al reported the diagnosability of fdg - pet for esophageal cancer as having a sensitivity of 92% , a specificity of 94% , and an accuracy of 93% . when comparing those numbers to bone scintigraphy , whose diagnosabilities are 77% , 84% , and 82% , respectively , the diagnosability of fdg - pet is superior , especially for osteolytic lesions .\nbut 2 false positives out of 44 cases came from pet , showing that fdg - pet is not perfect .\nthe suvmax of metastic tumor might be helpful to increase the accuracy of pet / ct .\nour previous study demonstrated that the suvmax of the primary tumor was positively correlated with tumor size and vessel invasion and was positively related to the suvmax of metastic tumor . in the report , the diagnostic accuracy of pet / ct ( 87.3% ) was higher than that of conventional ct scans . when diagnosing metastatic bone tumors , the positive predictive value of bone metastasis is known to be quite high if the findings for both pet and ct match .\ntherefore , even when bone metastasis is suspected due to abnormal fdg accumulation after a fdg - pet , yet no bone destruction image is found in the same site by ct , then interventional radiology or a surgical biopsy should be conducted to obtain a pathological diagnosis .\nthis case report was on 3 patients with suspected metastasis due to a false - positive pet / ct who were later confirmed to not have metastasis .\nthe metastases were originally suspected after conducting a pet / ct before surgery to treat esophageal cancer or during the postoperative course .\nconducting a pet / ct is useful when diagnosing esophageal cancer metastasis , but there should be an awareness of the possibility of false positives .\ntherapeutic decisions should be made based on appropriate and accurate diagnoses , and a pathological diagnosis should be actively introduced if necessary .", "answer": "of 129 esophagectomies at our institute from june 2010 to march 2015 , we experienced three preoperative positron emission tomography - computed tomographic ( pet / ct ) false positives . \n bone metastasis was originally suspected in 2 cases , but they were later found to be bone metastasis negative after a preoperative bone biopsy and clinical course observation . \n the other cases suspected of mediastinal lymph node metastasis were diagnosed as inflammatory lymphadenopathy by a pathological examination of the removed lymph nodes . \n conducting a pet / ct is useful when diagnosing esophageal cancer metastasis , but we need to be aware of the possibility of false positives . \n therapeutic decisions should be made based on appropriate and accurate diagnoses , with pathological diagnosis actively introduced if necessary .", "id": 65} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe success of valproic acid ( vpa , 2-propylpentanoic acid ) , a short branched chain fatty acid , for the therapy of absence seizures , partial seizures , tonic - clonic seizures , bipolar disorder , schizoaffective disorder , social phobias , neuropathic pain and for the prophylaxis and treatment of migraine headaches has spurred investigation for its use in the treatment of other conditions .\ntreatments for encephalopathy secondary to hyperammonemia as a side - effect of vpa treatment remain empirical and restoration of possible hepatic carnitine deficiency remains controversial .\nwhile some authors have found a positive correlation between plasma ammonia level and vpa dose or concentration others have found none .\nher elevated vpa levels were associated with elevated ammonia levels as expected of a positive correlation .\nin contrast , later on in the patient 's clinical course her raised venous ammonia levels were found to be slowly down - trending in the presence of sub - therapeutic serum vpa .\nthe present case report is about a 25-year - old hispanic female with a history of depression since age of 12 years , bipolar disorder , borderline personality disorder , purging type bulimia and history of suicide attempts at age 12 was admitted to the intensive care unit after attempted suicide by consuming an unknown number of vpa pills .\nthis patient had recently started taking vpa ( depakote ) as a mood stabilizer at a dose of 250 mg at bed time about 3 days earlier , after a failed therapy .\npatient was taking paroxetine 20 mg for depression ; this was incremented to 40 mg at the time vpa was started .\nshe reported that the change to vpa made her listless , lowered her mood , decreased her motivation , worsened her depression and caused suicidal thoughts .\nshe overdoses herself on vpa which she took with alcohol . after ingesting the pills she notified her family who then brought her to the emergency room . on admission ,\nher vitals were stable ( blood pressure : 118/72 mm hg ; temperature : 98.7f ; pulse : 82 beats / min ; oxygen saturation : 99% on room air ) . on initial examination\nshe looked disheveled , although drowsy , was oriented to person , place and time .\nthe complete blood count and comprehensive metabolic panel that was recorded initially and subsequently were unremarkable [ table 1 ] .\nsubsequently , she was administered oral lactulose once and then 1400 mg of levocarnitine orally every 6 h for the next 2 days . her vpa levels which peaked after admission continued to trend down over the next 4 days\n, the ammonia levels also peaked subsequent to admission then showed an initial dip followed by a very slow down - trend [ figure 1a ] .\nthe normalized log - linear plot of vpa serum concentration over time showed a down - trending linear first - order kinetics with a calculated t = 15.08 h [ figure 1b ] ( expected t for depakote : 9 - 16 h following oral dosing regimens of 250 - 1000 mg . the serum ammonia normalized log - linear plot in contrast showed two different decay kinetics : initial sharp down - trend for vpa levels greater than 90.9 g / ml but much slower downtrend for vpa levels less than 90.9 g / ml down into the subtherapeutic range of 8.5 g / ml .\npatient continued to complain of lethargy for the next 4 days which subsequently alleviated . at 14 days\nlaboratory values of the patient at the time of admission ( a ) valproic acid ( vpa ) and ammonia levels as a function of time ( days ) .\nvertical axes : straight line ( left ) : vpa levels ; dashed line ( right ) : venous ammonia levels .\n( b ) logarithm of normalized vpa and ammonia levels as a function of time in days .\nthe normalization for each compound , for levels at each recorded time point ( x ) was to its recorded maximum level ( xmax ) .\nthe normalized log - linear plot of vpa showed linear first - order decay kinetics with a calculated t = 15.08 h ( r = 0.994 )\nrecognition of symptoms of hyperammonemia remains a challenge especially in psychiatric patients . in a review of 11 case reports of symptomatic hyperammonemia in a psychiatric setting it was noted that acute hyperammonemic encephalopathy in psychiatric patients may present in various ways , sometimes with subtle clinical features .\nthe previously reported spectrum of clinical features included : improvement in mood , worsening of psychiatric symptoms , mild complaints of fatigue and delirium . in our patient ,\nhyperammonemia secondary to vpa overdose caused listlessness , lowering of mood , decreased motivation , worsening depression and suicidal ideation .\nwe observed presence of vpa in serum caused increased venous ammonia levels , which eventually trended down to normal after its cessation .\nincreasing vpa levels in serum was associated with increasing venous ammonia levels initially [ figure 1 ] .\nthe peak concentration of ammonia noted was likely a decrement from the real peak based on the time to peak of depakote tablets being 4 h ( the patients initial vpa levels were measured at 2 h after she allegedly consumed the vpa while the next blood draw was 9 h later ) .\nwe also made the following observations : ( 1 ) raised venous ammonia levels may remain symptomatic for a significant period of time beyond discontinuation of vpa .\n( 2 ) existence of more than one concurrent mechanism with different decay kinetics in the metabolism of ammonia in presence of high or low concentrations of serum vpa .\nunmasking of an inherent urea cycle metabolic disorder could have amplified the differential decay rates of venous ammonia .\nthe possibility of more than one mechanism causing hyperammonia secondary to vpa use is suggested by the different proposed mechanisms of vpa metabolites causing hyperammonemia , these include : ( 1 ) propionic acid inhibiting the urea cycle enzyme carbamoyl phosphate synthetase i ; ( 2 ) valproyl - coa or a closely related compound as a proximate inhibitor of mitochondrial ureagenesis ; ( 3 ) valproyl - carnitine ester causing a relative carnitine deficiency and ( 4 ) 2,4-dien - vpa inhibiting b - oxidation .\nalthough , we can not speculate on the mechanisms responsible for the different kinetics of decay of ammonia levels in the presence of down - trending vpa levels we can confidently state that non - elevated hepatic enzymes and hyperammonemia despite carnitine replacement indicated that hepatic damage and carnitine deficiency had very little role in causing the slowly down - trending elevated ammonia levels in the presence of subtherapeutic serum vpa levels .\nhyperammonemia and psychiatric disturbance secondary to valproate use in our case showed a score of 9 by a naranjo algorithm , indicating strong causality with the drug and placing it in causality category of definite . \nour assessment of a high adverse reaction probability scale was based on the fact that there are previous conclusive reports of hyperammonemia secondary to vpa use with similar psychiatric features as presented in this case report , hyperammonemia occurred only after vpa use and eventually trended down to normal levels with discontinuation of vpa , patients psychiatric disturbance correlated with hyperammonemia , the patient symptomatically improved with drug discontinuation , there are no alternative explanation of hyperammonemia and altered mood in this case , the serum levels of vpa were elevated with concentrations known to be toxic and that toxic effects observed were more severe with high dose and less severe when secondary hyperammonemia decreased .\nthis case report suggests that hyperammonemia , which is known to occur in about 50% patients treated with vpa , may have more than one concurrent etiologic mechanism with different decay kinetics which are not related to hepatic damage or carnitine deficiency .", "answer": "valproic acid ( vpa ) has successfully been used in the therapy of a number of conditions including absence seizures , partial seizures , tonic - clonic seizures , bipolar disorder , schizoaffective disorder , social phobias , neuropathic pain and migraine headaches . \n there is a high rise in number of cases of toxicity due to overdose of vpa . \n hyperammonemia , a common side - effect of vpa , is caused by several proposed etiologies , reported as having uncertain correlation with vpa dose or concentration . \n we present here a case of a 25-year - old female patient with a past history of psychiatric complaints , presented with elevated serum vpa levels associated with elevated venous ammonia levels subsequent to vpa overdose . later in the presence of sub - therapeutic serum vpa levels \n her venous ammonia levels remained raised and slowly down - trending . \n vpa levels and ammonia levels were found to be normal after 14 days . \n patient was treated with levocarnitine . \n her liver enzymes were never elevated . \n different decay kinetics of venous ammonia in presence of high and low concentrations of vpa indicates that vpa can cause symptomatic hyperammonemia via more than one concurrent etiological mechanism . in this patient , \n the mechanisms causing hyperammonia secondary to vpa use were not related to hepatic damage or carnitine deficiency .", "id": 66} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntopical steroid - dependent face is a common condition resulting from misuse of topical steroids over the face which may lead to erythema , burning and scaling .\n. the common indications are conditions such as psoriasis , lichen planus , eczema , lichen simplex chronicus , and other steroid - responsive dermatoses . however , because of their property of producing bleaching and anti - inflammatory effect , they have been misused frequently .\nthey are misused for varied indications such as acne , pigmentation , fungal infection , pruritus , and many a times as a cosmetic or a skin cream for any type of rash .\nthe main reason for such misuse in our country is its free availability as an over - the - counter ( otc ) medication .\nfurthermore , topical steroids are available in various irrational combinations which cause more damage to the skin . there are studies which have tried to highlight the various side effects and harm caused by misuse of topical steroids and its combinations .\nthese studies have tried to bring to the notice of regulatory authorities about the damage caused by the free availability of these creams . in this study , we have tried to find out the awareness among patients about these drugs and also as to how many of them have used these medicines .\nthis was a prospective study conducted at the dermatology outpatient department ( opd ) in a tertiary care hospital .\na total of 1000 adult patients attending the dermatology opd were included in the study . each patient attending the dermatology opd irrespective of their complaints\nthe questions mainly tried to find out if the patients had ever heard about the commonly abused topical steroids and its combinations ( betnovate , skinlite , melacare , panderm , fourderm , lobate gm , quadriderm ) in our area and if they had used any of those creams .\nthey were also asked about usage of any other creams other than the ones mentioned in the list .\nfurthermore , they were asked regarding who suggested those creams to them , the duration of usage , and if they noticed any side effect .\npatients < 18 years and those not willing to answer the questionnaire were excluded from the study .\na total of 1000 adult patients ( male : 360 , female : 640 ) were included in the study .\neight hundred and nine patients out of the 1000 patients had heard about at least one of the topical steroids mentioned in the questionnaire .\nsix hundred and twelve patients ( 400 female and 212 male ) had used the topical steroid or its combination for various indications [ table 1 ] .\nbrand names of the topical steroid - containing products the indications for which these medicines were used included acne ( 30.2% ) , allergy ( 14.8% ) , pigmentation ( 11.4% ) , boils ( 0.3% ) , eczema ( 0.98% ) , fairness ( as cosmetic 10.8% ) , fungal infections ( 3.4% ) , injury ( 3.5% ) , itching ( 11.7% ) , oily skin ( 0.65% ) , skin rashes ( 7.1% ) , white patches ( 1.9% ) , and burns ( 0.32% ) .\nacne was the most common indication for which topical steroid was used , followed by allergy and rashes . around 66 ( 10.8% ) patients were using these medicines as a cosmetic for fairness and 70 ( 11.4% ) patients were using it to remove pigmentation due to various reasons .\noverall 52.4% of patients were using these creams mainly over the face and rest of them were using it over other parts of the body as a general skin cream for any rashes .\nfriends had suggested these medicines in 191 ( 31.2% ) patients , followed by pharmacists in 71 ( 11.6% ) patients .\nthe duration of the usage of these creams varied from 1 day to 10 years . around 383 ( 62.5% )\npatients had used these creams for a duration varying from 1 week to 3 months .\none hundred and seven ( 17.4% ) patients had used these creams from 3 months to 2 years .\nthree hundred and eighteen ( 51.9% ) patients complained of some form of side effect after using these creams .\none hundred and twenty - seven patients complained of aggravation of symptoms , 65 patients complained of increased pigmentation [ figure 1 ] , 26 patients developed pimples [ figure 2 ] , and redness and irritation was seen in 74 patients .\nother minor side effects included white patches , burning sensation , and no improvement of the skin problem [ table 2 ] .\npigmentation due to use of topical steroid adverse effects as complained by the patients using topical steroids\ntopical steroids were first used in dermatology by sulzberger and witten in 1952 when they published an article on the effect of topically applied compound f in selected dermatoses .\ntopical steroids have greatly contributed to the dermatologist 's ability to effectively treat several difficult dermatoses .\nthey were hailed as a panacea for all ills by physicians and patients and gained rapid popularity .\ntopical steroids are one of the most commonly used drugs by dermatologists worldwide . however , the dramatic symptomatic relief from these medications led to misuse and abuse of these drugs by both nondermatologists and patients .\nthe rampant misuse and abuse of these medicines led to the development of various side effects , both cutaneous and systemic .\nvarious studies have tried to highlight the menace caused by the use of topical steroids . a multicentric study by saraswat et al .\nhas also been done to highlight the topical steroid abuse on the face . around 2296 patients with facial dermatoses\nwere screened , of which 433 patients were using topical steroids . in our study , we have included 1000 adult patients attending dermatology opd irrespective of their skin complaints .\nwe have tried to find out how many patients have heard about any of the common topical steroids available otc in our area and also how many of them have used these creams . around 809 patients ( 80.9% ) had heard of at least one of the topical steroids or its combinations .\nsix hundred and twelve ( 61.2% ) patients had used one of the steroids or steroid combinations for a duration varying from 1 day to 10 years .\nthe common indications for which steroid was used were acne , fairness ( as cosmetic ) , pigmentation , and allergy .\nthe findings are similar to the study conducted by saraswat et al . and dey .\nan iraqi study showed 7.9% of patients using topical steroid for similar indications . in our study , 302 ( 49.5% ) patients who had used the steroid had received the prescription from a doctor . in the study by saraswat et al .\n, 41% of the patients had received the recommendation from a doctor . in the present study , 301 ( 49% )\npatients were advised to use these medicines by pharmacists , friends , and relatives . however , most of the time , general practitioners and doctors from alternative medicine had prescribed these medicines .\ngeneral practitioners and pharmacists are often the first point of contact for most of the patients .\ntraining and sensitizing them regarding steroid abuse would help in reducing the incidence of topical steroid - related side effects .\nthe common side effects found in our study were acne , pigmentation , redness , itching , burning sensation , striae , and aggravation of existing skin problem .\nthese are similar to the findings by saraswat et al . and dey . the nature of side effect correlated with the duration of the usage of topical steroid .\nhowever , many of our patients were not aware of the fact that the problems they were facing were due to the long - term use of steroids .\nfrom the findings of our study and other studies , we would like to conclude that topical steroid abuse is rampant in our population .\nthe reason for this varies from wrong prescription , dubious marketing by pharmaceutical companies , free availability of these medicines as otc drugs , and lack of regulations regarding the manufacturing of irrational combinations .\nas general practitioners and pharmacists are recommending these products in majority of the cases , it is very important to sensitize these people about the possible complications of these drugs and the extent of problem the society is facing because of irrational and unregulated use of these drugs .\nour study aims to highlight the misuse of steroids and its combination anywhere on the body .\nour study was an outpatient - based study , and further larger studies will give a clearer picture about the magnitude of the steroid abuse .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\ntopical steroid abuse is not only limited to the face but also over the rest of the body .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\ntopical steroid abuse is not only limited to the face but also over the rest of the body .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\ntopical steroid abuse is not only limited to the face but also over the rest of the body .", "answer": "background : topical steroids are one of the most commonly abused drugs . \n there are only a few studies available which have highlighted the severity of this problem in india . \n however , these studies have concentrated mainly on the topical steroid abuse and its side effects over the face.aims:the aim of this study was to know the awareness among the people about various commonly available topical steroids and their combinations irrespective of usage and to know the extent of misuse of these drugs . along with this \n , we also tried to find the source of recommendation of these medicines which will help to sensitize people about this menace.materials and methods : this was a prospective , questionnaire - based study done at a tertiary care hospital . \n a total of 1000 adult patients attending the dermatology outpatient department were administered a questionnaire about awareness and usage of topical steroid and its combinations.results:a total of 1000 adult patients were included in the study , out of which 809 ( 80.9% ) patients had heard about at least one of the topical steroids or its combinations mentioned in the questionnaire . \n six hundred and twelve ( 61.2% ) patients had used these creams . \n acne and pigmentation were the most common indications for which topical steroid was used . \n these medicines were recommended by general practitioners in 302 ( 49.5% ) patients and pharmacists in 71 ( 11.6% ) patients . \n totally , 318 ( 51.9% ) patients complained of some form of side effect after using these creams . \n aggravation of the symptoms and increased pigmentation were the most common adverse effects.conclusion:misuse of topical steroids not just over the face but also as a cream for any skin problem is quite common . \n most of the times , it is recommended by general practitioners or pharmacists . \n it is very important to sensitize these people about the possible complications of these drugs and the extent of problem the society is facing because of irrational and unregulated use of these drugs .", "id": 67} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhidradenomas are benign cutaneous tumors of sweat gland origin , with the clear cell type constituting the most frequent histologic variety . usually , they are diagnosed in the elderly population , the peak incidence being the fifth to sixth decade .\nwe describe a young girl , in whom nodular hidradenoma developed at the age of 6 years .\nhence , our case demonstrates that nodular hidradenoma is a rare differential diagnosis of skin tumors , even in the pediatric age group .\na 10-year - old girl presented to us with a swelling on the left thigh , which had been progressively enlarging over the preceding 4 years .\ncutaneous examination revealed a solitary erythematous dome - shaped , well - circumscribed tumor , measuring approximately 6 cm 4.5 cm .\nthere was spontaneous dripping of straw - colored serous fluid at the rate of 2030 drops / min , the discharge accentuating on pressure .\nbiochemical analysis of the serous fluid revealed glucose 25 mg / dl , protein 4 g / dl , sodium 131 mmol / l , and potassium 4.3 mmol / l , almost similar to that of serum , the low concentration of glucose compelling us to think of something else . the mass was excised .\nthe solid portion was largely composed of a cell type having finely granular , faintly eosinophilic cytoplasm with a dark - colored round to oval nucleus .\nthe cyst was lined by a single layer of cuboidal epithelium without evidence of decapitation secretion [ figure 5 ] .\nsolitary dome - shaped , well - circumscribed tumor over the left thigh photomicrograph showing a well - encapsulated mass composed of solid and cystic portions ( h and e , 40 ) photomicrograph showing a well - encapsulated mass with large cystic spaces within it .\nductal luminal structures can be appreciated ( h and e , 100 ) photomicrograph showing clear cells in the center along with cystic spaces ( h and e , 400 ) note the large cystic cavity within the mass .\nclear cell hidradenoma or eccrine acrospiroma of the skin was first described by liu , in 1949 , as clear cell papillary carcinoma of the skin .\nit was reported under various designations such as nodular hidradenoma , eccrine acrospiroma , solid - cystic hidradenoma , clear cell acrospiroma , clear cell myoepithelioma , and eccrine sweat gland adenoma .\nclinically , nodular hidradenoma presents as a slow - growing , red- , blue- , or brown - colored solitary , 530 mm in size , freely mobile and firm nodule , with an occasional cystic appearance .\nthese are most commonly found on the scalp , face , thorax , abdomen , and gluteal region .\nthis tumor is found mainly in adults and is excised more commonly in women than in men .\nour patient was a young girl who presented with a gradually increasing swelling on the lower limb , a site that is unusual for the development of nodular hidradenoma .\nliterature search showed very few cases of nodular hidradenoma on the lower limb , that too in the pediatric age group .\nhowever , a case of nodular hidradenoma masquerading as umbilical polyp has been reported in a 1-year - old male child\nour patient complained of serous discharge from the lesion , for the preceding 3 months .\nclinical differential diagnoses for our case were cutaneous lymphoma , dermatofibrosarcoma protuberans , epidermoid cyst , and sweat gland tumor . however , histology reliably excluded all the possibilities .\nit was predominantly composed of a cell type having finely granular , faintly eosinophilic cytoplasm with a dark - colored round to oval nucleus .\nthe chronically discharging nature of the tumor in our patient was attributable to the fluid - filled cavity within the lesion .\nbiochemical analysis of the fluid was almost consistent with that of serum , however , the low concentration of glucose hinted that it might be normal sweat .\nrecently , nuclear grooving has been described as a useful morphological feature to aid in its diagnosis .\nimmunohistochemical staining of the tumor cells demonstrates positive staining with antibodies against ck - cam 5.2 , ber - ep4 , p63 , epithelial membrane antigen , s-100 protein , smooth muscle actin , and vimentin .\nhowever , due to unavailability of resources and financial constraints , the immunohistochemical analysis could not be performed in our case .\nthe high rate of local recurrence ( 10% ) and potential for malignant transformation make surgical removal with wide margins as the widely accepted modality of treatment .\nthe high recurrence is attributable to incomplete resection and to tumor tissue located between the dermis and subcutaneous tissue .\nthese are characterized by increased mitotic activity , angiolymphatic invasion , local extension into deeper tissues , and a dispersed pattern of growth .\nnodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting . \n \nnodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .\nnodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting . \n \nnodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .\nnodular hidradenoma in the pediatric age group is extremely rareit is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limbthe presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting . \n \nnodular hidradenoma in the pediatric age group is extremely rare it is usually located over the head , neck , and trunk . in our case ,\nthe lesion was present in the lower limb the presence of an unusually large cystic cavity within the tumoral mass , leading to serous discharge , makes our case even more interesting .", "answer": "a 10-year - old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion . based on histological features of the excised tumor , a diagnosis of nodular hidradenoma was made . \n atypical features including large size of the tumor , location on the lower limb , a weeping presentation , and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case .", "id": 68} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhaemolytic uraemic syndrome ( hus ) is most frequently caused by infection with shiga toxin - producing strains of escherichia coli or shigella dysenteriae type 1 .\nother causes include inherited and acquired abnormalities affecting the alternative pathway of complement , other infections and certain drugs , including cisplatin and carboplatin .\nrecently eculizumab , a humanized monoclonal antibody directed against c5 that prevents the activation of the terminal complement pathway , has been shown to be an effective treatment for patients with atypical hus ( ahus ) .\nthrombotic microangiopathy has long been recognized as a complication of disseminated cancer and cisplatin therapy .\nthe acute form has a high mortality rate , although successful treatment with plasma exchange has been described [ 2 , 7 , 8 ] .\na previously well 27-month - old boy with no family history of kidney disease presented with a cervical mass unresponsive to antibiotics . the plasma lactate dehydrogenase ( ldh ) was elevated at 1600 iu / l ( normal 266500 ) .\nbone marrow examination and metaiodobenzylguanidine ( mibg ) scan showed no evidence of distant metastases .\npre - treatment , the plasma creatinine concentration was 21 mol / l , and the glomerular filtration rate ( gfr ; measured by plasma disappearance of technetium ( tc)-99 labelled diethylene triamine pentacaetic acid ( dtpa ) was 107 ml / min/1.73 m body surface area .\ntherapy was started with a combination of vincristine , etoposide , carboplatin , cisplatin and cyclophosphamide . on day 45 of treatment ( 35 days after the first cisplatin dose , 15 days after the second )\n, the gfr had fallen to 60 ml / min/1.73 m. this was presumed to be due to acute cisplatin nephrotoxicity .\nthe hypertension became increasingly severe ( maximum value recorded 160 mmhg systolic ) and he required five agents to control the blood pressure .\nhe required seven infusions of platelets and four of red blood cells between days 50 and 59 , suggesting that the pancytopaenia was not solely due to myelosuppression and the plasma creatinine concentration rose from 39 to 140 mol / l .\na blood film confirmed the presence of schistocytes , the ldh had risen to 2438 iu / l and the plasma haptoglobin concentration was < 0.06\ng / l ) and c4 ( 0.20 g / l ) concentrations were normal .\nrenal biopsy was considered unsafe at this time , but the results above were considered compatible with a diagnosis of hus , likely due to cisplatin . stool and blood cultures were negative , as were serological tests for hiv1&2 .\nadamts13 ( von willebrand factor - cleaving protease ) levels were 80% of control values . despite the dearth of information concerning the pathogenesis of cisplatin / carboplatin - associated chemotherapy , we opted for therapy with eculizumab partly because it was felt that his severe hypertension , profound thrombocytopaenia and small size made plasma exchange hazardous .\nhe received the first dose of 600 mg the following day when his plasma creatinine was 155\nthe next day the plasma creatinine peaked at 160 mol / l and it steadily decreased thereafter ( figure 1 ) .\nafter a further dose of 300 mg a week later , he was maintained on fortnightly doses of 300 mg according to the manufacturer 's dosing guidelines .\nfive weeks after administration of the first dose of eculizumab , the plasma creatinine concentration had reduced to 34\niu / l and the gfr was 67 ml / min/1.73 m. a decision was made to avoid further exposure to platinum - containing agents , and therapy was changed to a combination of vincristine , topotecan and doxorubicin .\nthere was little further change in tumour size and , 126 days after starting chemotherapy , the tumour was surgically removed with clear excision margins and eculizumab was discontinued . at this time , the platelet count was 181 10/l and the plasma creatinine concentration was 34\nthe platelet count fell to 138 four weeks after the last eculizumab dose and remained in the range of 98160 10/l for the next 2 months .\ntwo months after discontinuing the eculizumab , the plasma ldh had risen to 807 iu /\nthe plasma concentration of the terminal complement complex ( sc5b-9 ) was elevated at 137 ng / ml ( normal range < 80 ) .\nof the 20 glomeruli in the light microscopy sections , five were globally sclerosed , and two showed periglomerular fibrosis .\nthe patent glomeruli showed an increase in mesangial cells and matrix with segmental sclerosis and capsular adhesions .\nthe toludine blue preparation and electron microscopy ( em ) showed thickened glomerular capillary loops ( double contour appearance ) , and areas of widening of the sub - endothelial space were seen .\nthis marked widening of the sub - endothelial space and fibrillar / particulate material is characteristic of hus ( figure 2 ) . \n\nlight microscopy showing sclerosed glomeruli ( to the left of the figure ) and a glomerulus showing increased mesangial matrix expansion and segmental sclerosis ( boxed area ) .\nthere is also focal tubular atrophy around damaged glomeruli ( jones silver histochemical stain , scale bar = 10 m ) .\n( b ) high power light microscopy showing glomerulus with mesangial matrix expansion and segmental sclerosis ( asterisks ) ( jones silver histochemical stain , scale bar = 5 m .\n( c ) toludine blue semithin preparation showing increased mesangial matrix expansion and segmental sclerosis ( asterisks ) and thickened capillary loop ( arrow ) mimicking membranoproliferative glomerulonephritis , scale bar = 5 m .\n( d ) em showing fluffy - like material within a markedly widened sub - endothelial space consistent with hus scale bar = 2 m .\nlight microscopy showing sclerosed glomeruli ( to the left of the figure ) and a glomerulus showing increased mesangial matrix expansion and segmental sclerosis ( boxed area ) .\nthere is also focal tubular atrophy around damaged glomeruli ( jones silver histochemical stain , scale bar = 10 m ) .\n( b ) high power light microscopy showing glomerulus with mesangial matrix expansion and segmental sclerosis ( asterisks ) ( jones silver histochemical stain , scale bar = 5 m .\n( c ) toludine blue semithin preparation showing increased mesangial matrix expansion and segmental sclerosis ( asterisks ) and thickened capillary loop ( arrow ) mimicking membranoproliferative glomerulonephritis , scale bar = 5 m .\n( d ) em showing fluffy - like material within a markedly widened sub - endothelial space consistent with hus scale bar = 2 m .\nthe haematological , biochemical and histopathological features suggested active hus , and eculizumab was therefore recommenced with an initial dose of 600 mg given 105 days after the last dose . before restarting the eculizumab ,\nthe gfr was measured at 54 ml / min/1.73 m , the serum complement c3 concentration was 0.9\nthe total haemolytic complement ( ch50 ) was 111% , but the alternative pathway haemolytic complement ( ap50 ) was low at 34% ( normal 80200 ) .\ng / l ) , normal platelets ( 248 10/l ) and a plasma creatinine concentration of 32 mol / l .\nthe gfr had risen to 71 ml / min/1.73 m. the plasma concentration of sc5b-9 remained elevated at 133 ng / ml , casting doubt on the suitability of this assay for assessing activity and response to treatment .\ndna extracted from a buccal smear at the time of diagnosis of hus was amplified by pcr for all coding exons 10 bases of the cfh ( factor h ) , cfi ( factor i ) , c3 ( complement component 3 ) , cfb ( factor b ) and cd46 ( membrane cofactor protein , mcp ) genes .\namplified products were subjected to bi - directional sanger sequencing ( abi ) , as previously described .\ncd46 expression on cell surfaces was assessed on peripheral blood neutrophils after recovery from myelosuppression by flow cytometry using cd46 fluorescein isothiocyanate - conjugated antibody ( bd pharmingen , 555949 ) .\nan intronic sequence variant ( c.1027 + 5g > t ) was identified in cd46 .\nthis variant had not been previously reported nor was it detected in dna from 188 normal control subjects . in silico splicing prediction analysis undertaken using alamut ( interactive bioscience software , seine biopolis , 70 route de lyons - la - foret , 76 000 rouen , france ; http://www.interactive-biosoftware.com ) suggests that this variant may cause aberrant splicing .\nafter discussion with the parents , a decision was made not to test other family members , because the result was felt to be of limited clinical utility , outweighed by potential anxiety induced in a carrier .\nendothelial cells , glomerular basement membrane and podocytes all show ultrastructural evidence of damage after cisplatin exposure .\nopsonization of damaged or apoptotic cells with c3b plays an important role in the efficient removal of such cells by phagocytes , and there is evidence of complement activation in cisplatin - induced aki . on host cell surfaces ,\ndeposited c3b is usually rapidly inactivated by several regulatory proteins including cd46 ( mcp ) and factor h , both of which act as cofactors for factor i. deficiency or reduced activity of these complement regulatory proteins would potentially lead to amplification of the endothelial cell damage induced by cisplatin .\nahus is most frequently associated with impaired regulation of the alternate pathway of complement regulation on the surface of host cells with normal regulation in the fluid phase , and plasma c3 levels are therefore frequently normal . because endothelial damage is associated with complement activation and c5\nplays a pivotal role in the development of ahus , it seemed appropriate to initiate treatment with eculizumab .\nthe finding of a novel mutation causing decreased expression of cd46 suggests that dysregulated complement activation played an important role in pathogenesis . the response to eculizumab , deterioration on withdrawal of eculizumab and improvement after restarting treatment all support this hypothesis .\nour patient is the first to have genetic investigation of the factors involved in the regulation of the alternative pathway of complement regulation and the first to be treated with eculizumab .\nthe possibility that dysregulated complement activation underlies the thrombotic microangiopathy in other patients with cisplatin - induced hus should be considered , and testing for abnormalities of complement regulation should be performed in future patients .\nthe optimal duration of eculizumab therapy remains unclear ; 4 months of therapy was clearly inadequate in our patient but we hope to be able to withdraw treatment in the future .\nr.d.g . received a travel grant to attend the era - edta conference in paris in 2012 .", "answer": "a 2-year - old patient with a neuroblastoma developed haemolytic uraemic syndrome ( hus ) following treatment with cisplatin and carboplatin . following treatment with eculizumab \n , there was a substantial improvement in renal function with the recovery of the platelet count and the cessation of haemolysis . \n subsequent investigations showed a novel , heterozygous cd46 splice site mutation with reduced peripheral blood neutrophil cd46 expression . \n withdrawal of eculizumab was followed by the recurrence of disease activity , which resolved with re - introduction of therapy . \n abnormal regulation of complement may be associated with other cases of cisplatin - induced hus and treatment with eculizumab may be appropriate for other affected individuals .", "id": 69} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prevalence of obesity in children and adolescents is increasing world - wide , notably in developing countries .\nnow - a - days , this problem has become one of the important concerns about general health at the global level .\nobesity in childhood and adolescence has different effects on mental health , including symptoms of anxiety , depression , insomnia , social isolation etc .\n, in turn , these conditions would have negative consequences on social relationships and learning issues .\nsome studies documented higher prevalence of mental disorders as depression and anxiety in obese than in normal - weight individuals .\nin contrast , the prevalence of mental disorders is increasing in children around the world ; this can be due to the escalating trend of childhood obesity . due to the importance of mental health\n, it is considered as part of the world health organization global school - based health survey ( who - gshs ) .\nsimilar to most other developing countries , iran is facing double burden of nutritional disorders .\nsome studies in iran have considered the relationship of overweight and obesity with mental disorders . although most studies in western countries found a higher prevalence of psychiatric disorders in overweight children and adolescents , but studies conducted in two cities in iran did not document the relationship of body mass index ( bmi ) with depression and anxiety in iranian students .\nbecause of diversity in the cultural and socioeconomic background in different regions of iran , it is necessary to extrapolate such investigations in different parts of the country to help in designing and implementing health promotion programs .\nthis nationwide study aims to assess the relationship of excess weight with some mental disorders in iranian students by using the who - gshs questionnaire .\nthis nationwide cross - sectional study was conducted as part of the third national survey of a school - based surveillance system entitled the childhood and adolescence surveillance and prevention of adult non - communicable disease - iii study .\nafter explanation of the study aims and methods , verbal assent was obtained from students and written informed consent from their parents .\nthis study was conducted in 2009 - 2010 among 5570 students , aged range from 10 to 18 years .\nthey were selected by random cluster sampling from urban and rural areas of 27 provinces in iran .\nthe questions related to the mental distress are presented in appendix i. trained health professionals conducted the physical examination under standard protocols and by using calibrated instruments .\nbmi was calculated as weight ( kg ) divided by height squared ( m ) .\ncontinuous variables are expressed as mean ( standard deviation [ sd ] ) and categorical variables are presented as number ( percentage ) .\nlogistic regression analysis was used to assess the association of obesity and overweight with mental disorders .\ncontinuous variables are expressed as mean ( standard deviation [ sd ] ) and categorical variables are presented as number ( percentage ) .\nlogistic regression analysis was used to assess the association of obesity and overweight with mental disorders .\ntheir mean sd age was 14.7 ( 2.4 ) years , without significant difference in terms of gender .\ntable 1 shows the frequency of anxiety according to gender and bmi categories . according to their self - report\n, 3182 ( 58.7% ) students had anxiety , which consisted of 1417 ( 53.1% ) girls and 1765 ( 64.7% ) boys .\nno significant association was documented neither between overweight and anxiety ( odds ratio [ or ] : 0.86 , 95% confidence interval [ ci ] : 0.68 - 1.09 ) , nor between obesity and anxiety ( or : 1.11 , 95% ci : 0.88 - 1.40 ) . frequency of self - reported anxiety among iranian adolescents by gender and weight status : the caspian - iii study as can be seen in table 2 , 3389 ( 62.6% ) of students reported to have depression , they consisted of 1643 ( 61.1% ) girls and 1746 ( 64.3% ) boys reported to have depression .\nthere was no significant relationship between overweight and depression ( or : 1.11 , 95% ci : 0.86 - 1.43 ) and between an obesity and depression ( or : 1.01 , 95% ci : 0.79 - 1.29 ) . the self - reported frequency of insomnia among students is presented in table 3 .\nit shows that 2618 ( 49.4% ) of students consisting of 1285 ( 49.1% ) girls and 1333 ( 49.7% ) boys had insomnia .\nno significant relationship was found neither between overweight and insomnia ( or : 1.17 , 95% ci : , 0.91 - 1.51 ) , nor between obesity and insomnia ( or : 0.91 , 95% ci : 0.71 - 1.17 ) .\nfrequency of self - reported depression among iranian students by gender and weight status : the caspian - iii study frequency of self - reported insomnia among iranian students by gender and weight status : the caspian - iii study\nthis study , which is the first nationwide study of its kind in iran , showed that overweight and obesity were not associated with depression , anxiety and insomnia in iranian adolescents .\ncontrary to our findings , several studies in western countries have documented higher prevalence of these mental disorders in overweight and obese individuals .\nthese differences could be because of social and cultural differences , especially the attitude of friends , family members and the community to obesity and obese person in various societies .\nsimilar to previous studies in iran , our findings propose that overweight and obesity in adolescence are well - accepted by the community and therefore the overweight or obese person is not under pressure by parents and peers .\nsome previous studies have suggested that obese children , who are mocked by their friends , would experience some negative feelings including shame , isolation and depression .\nmoreover , these studies proposed that pressure and sneap imposed by parents is increased in overweight and children and adolescents .\nit is also suggested that depression might lead to unhealthy behaviors and in turn might result in overweight and obesity .\nthe current study showed that anxiety and depression are more prevalent in boys than in girls .\nsome previous studies reported higher prevalence of such disorders in 12 - 18-year old girls and 10 - 12-year old boys .\nthey suggested that such differences might be because of hormonal changes during puberty . in another study ,\ndepression was reported to be more prevalent in girls with 15 - 18 years of age and boys aged 10 - 14 years .\nfurther studies shall be conducted about the effects of various items including genetic , environmental , cultural , social and nutritional factors on gender differences documented by various studies about the psychiatric distress during adolescence .\nthe present study did not find any significant difference in the prevalence of insomnia according to gender and weight status .\nsome studies documented higher prevalence of insomnia in girls and obese individuals . in our study , the prevalence of depression and anxiety was more than a previous study in iran , however , our finding is consistent with some other studies . study limitations and strengths : the main limitations of this study are its cross - sectional setting and using self - reported data on psychiatric distress among adolescents .\nthe main strengths are the novelty in the region , recruiting a large sample size of adolescents from diverse parts of the country , as well as using an internationally accepted questionnaire .\nwe did not find significant relationship between excess weight and psychological distress in iranian students .\nthis can be because of positive attitude of iranian families toward fatness in childhood and adolescence .", "answer": "background : excess weight may be associated with mental distress and this relationship varies according to the socio - cultural background of different populations . \n this study aims to assess the relationship of overweight and obesity with some psychological disorders in a nationally representative sample of iranian adolescents.methods:this nationwide study was conducted in 2009 - 2010 among 5570 students , aged 10 - 18 years , living in 27 provinces in iran . \n data were collected by using the translated and validated questionnaire of the world health organization global school - based health survey.results:data of 5528 students ( 49.7% girls ) were complete for this study . \n their mean age was 14.7 ( 2.4 ) years . \n overall 7.9% of participants were overweight and 8.8% were obese . \n 58.7% of students had anxiety , without significant association of overweight ( odds ratio [ or ] : 0.86 , 95% confidence interval [ ci ] : 0.68 - 1.09 ) and obesity ( or : 1.11 , 95% ci : 0.88 - 1.40 ) with an anxiety . \n nearly 62.6% of students reported to have depression , there was no significant relationship between overweight ( or : 1.11 , 95% ci : 0.86 - 1.43 ) obesity and ( or : 1.01 , 95% ci : 0.79 - 1.29 ) with the depression . \n about 49.4% of students had insomnia , without significant association of overweight ( or : 1.17 , 95% ci : , 0.91 - 1.51 ) and obesity ( or : 0.91 , 95% ci : 0.71 - 1.17 ) with the insomnia.conclusions:in iranian adolescents , excess weight did not increase the risk of psychological distress . \n this finding might be due to the positive attitude of family and peers to fatness in adolescence .", "id": 70} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchest pain is a typical symptom of acute coronary syndrome ( acs ) , of which there are three common types : unstable angina ( ua ) , st segment elevation ( stemi ) of myocardial infarction ( mi ) , and non - st - segment elevation of mi ( nstemi ) [ 1 , 2 ] .\nsymptoms of acs in the absence of chest pain are dyspnea , nausea , sweating , neck or jaw and arm pain .\near pain and sore throat are rare symptoms of acs , which makes diagnosis and treatment difficult and challenging .\nwe present a rare case of a patient presented to the emergency department of our hospital with symptoms of earache and sore throat for cardiac ischemia .\na 53-year - old african - american female presented to the ed complaining of earache and sore throat for 3 days .\nshe described the pain as a burning sensation that was worst when she woke up in the morning and got better as the day progressed .\nthe patient denied chest pain , shortness of breath , nausea , vomiting , or dizziness .\nthe patient worked as a telemarketer , described her job as very stressful , and claimed to smoke one to two cigarettes per week .\nher medical history was significant for dyslipidemia , newly diagnosed type 2 diabetes , and chest discomfort diagnosed 4 months ago at a different hospital as stemi with complete occlusion of the rca .\nshe was treated at the hospital by placement of a bare - metal stent in her rca .\ncurrent home medications included clopidogrel , aspirin , statin , beta - blocker , metformin , and nitroglycerin sublingually as needed for chest pain .\nher vital signs on arrival at the ed were : bp of 131/82 mmhg , pulse of 70 beats per minute , respiratory rate of 17 breaths per minute , temperature of 98 f , and oxygen saturation of 98% on room air . because of multiple risk factors , in addition to a symptom that could potentially be a referred cardiac pathology , an ecg , chest radiograph , and cardiac biomarkers were ordered at the triage .\ncardiovascular , pulmonary , abdominal , ear , nose , and throat examinations were unremarkable .\nthe initial ecg displayed no st segment elevation , but t wave inversion in inferior leads that was unchanged from a previous ecg .\na presumptive diagnosis of acs/ nstemi was made on the basis of an elevated troponin combined with the ecg changes .\nafter the acs protocol was initiated , a cardiology consultation was requested , and the patient was admitted to our hospital . on admission ,\nthe patient continued to complain of throbbing ear pain that fluctuated now between the two ears , but again denied chest pain or shortness of breath . on the 2nd day\nit was found that the previous bare - metal stent in the posterolateral branch ( distal rca ) was completely occluded , and no balloon could be advanced beyond that area .\na new lesion in the proximal / ostial rca greater than 70% occlusion was opened with a successful placement of a pci at the ostial rca using a drug - eluting stent . following this ,\nher troponin level had declined to 0.63 ng / m on the 3rd day , and the patient was discharged with a referral for cardiac rehabilitation .\nwe concluded on follow - up that otalgia in this patient was an atypical symptom of referred angina pain .\nthe patient was seen 2 weeks later at the cardiology clinic of our hospital and reported no complaints about her condition or recurrence of ear pain .\nan ecg revealed no changes from the previous one done 2 weeks earlier at the time of discharge .\nthe underlying pathophysiology of the referred otalgia in this patient can be explained by the autonomic dysfunction of the auricular branch of the vagus nerve often termed alderman s nerve .\nthis branch of the vagus innervates the inner portion of the outer ear , and also controls the skeletal muscles including the superior , middle and inferior pharyngeal constrictors . the sinoatrial ( sa ) node\nwe suggest that partial occlusion of the rca promoted damage of the parasympathetic fibers of the right vagus , and was the cause of referred otalgia and pharyngitis in our patient .\nsensory nerves are affected by type 2 diabetes [ 47 ] , but whether such a preexisting condition predisposes a person to angina - referred otalgia or pharyngitis is not clear . to our knowledge ,\nsymptoms of ear pain for cad and acute arterial occlusion in a patient have rarely been discussed in the literature .\nwe found only one report ; in this report the correct diagnosis of cardiac ischemia was missed in two patients who were initially treated for primary ear pain . in conclusion , clinicians should be aware and recognize that ear and throat pain may represent symptoms for cardiac ischemia .", "answer": "a rare case of a patient with unusual symptoms of earache and sore throat for cardiac ischemia is presented . \n a diagnosis of non - st - segment elevation myocardial infarction ( nstemi ) was made based on initial elevation of troponin and an abnormal electrocardiograph ( ecg ) . \n percutaneous coronary intervention ( pci ) performed with stent placement in the occluded coronary vessel was followed by a decrease in troponin level and complete resolution of the ear and throat pain and patient recovery from cardiac ischemia .", "id": 71} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe structures of acl and mcp in the gas phase were optimized at the b3lyp/6 - 31 g * level .\nthe structures of the water clusters were determined with classical molecular dynamics trajectories ( see details in the si ) .\nthe cluster models include solvents that have at least one of the atoms within 3 and 4 from acl and mcp , respectively . the geometry of the acl and mcp in the water clusters was further optimized at the b3lyp / cc - pvdz and cam - b3lyp / cc - pvdz levels , respectively . in the optimization ,\nthe water molecules were fixed at the md structure and replaced by point - charges ( tip3p charges ) .\nwe also fixed the c atom next to the o atom of acl . in mcp , the atomic coordinates of the central c atom were fixed .\nthe hf orbitals were transformed into mos localized within each fragment ( solute and solvent ) .\nour transformation uses reference orbitals ( rmos ) obtained with external calculations for isolated molecules .\n, we show the populations at the fragments . in the perturbation - selection step of the sac - ci calculations , a set of threshold , levelfour ,\nas a service to our authors and readers , this journal provides supporting information supplied by the authors .\nsuch materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors", "answer": "intermolecular interactions regulate the molecular properties in proteins and solutions such as solvatochromic systems . some of the interactions have to be described at an electronic - structure level . in this study , \n a commutator for calculating the excitation energy is used for deriving a first - order interacting space ( fois ) to describe the environmental response to solute excitation . the fois wave function for a solute - in - solvent cluster \n is solved by second - order perturbation theory . \n the contributions to the excitation energy are decomposed into each interaction and for each solvent .", "id": 72} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbrown sequard syndrome resulting from compression due to an epidural hematoma is a relatively rare occurrence , more so with a spontaneous history .\nshe underwent an open door laminoplasty for evacuation of the hematoma . following surgery the patient responded rapidly and currently at 18 months\nin the emergency room when a patient is clinically diagnosed as a case of brown sequard syndrome it is important to ask for an mri scan of the cervical spine .\nhematoma in the cervical epidural space should be considered in the differential diagnosis of brown sequard syndrome especially in the elderly with history of doubtful trivial trauma .\nbrown sequard syndrome is an incomplete spinal cord lesion characterized by a clinical presentation reflecting hemi - section of the spinal cord .\nthis is referred to as ipsilateral hemiplegia and contralateral pain and temperature sensation deficits ( anaesthesia ) .\nthe most common cause is penetrating trauma such as a gunshot wound or stab wound to the spinal cord , however spinal tumours and blunt trauma to the spine have also been implicated as potential causes .\nhematoma is also a cause of brown sequard syndrome but is very rare and usually occurs with predisposing risk factors for bleeding ( anticoagulant therapy , hypertension ) .\nbrown sequard syndrome as a result of cervical epidural hematoma is a rare entity with only a handful of cases reported in literature .\nwe describe a case of brown sequard syndrome in a 65 year old female without any underlying risk factors , presenting with sudden onset hemiparesis rapidly progressing to hemiplegia ( within a span of days ) due to a cervical epidural hematoma following a doubtful history of trivial trauma .\na previously healthy 65 year old female presented to us with the complaint of right side hemiplegia without any significant history of trauma . on subsequent inquiry\nshe gave a history of brisk involuntary hyperextension of the neck following which she developed sudden onset hemiparesis , progressed to hemiplegia within a span of five days .\nshe did not have a history of any congenital or acquired disorder of coagulation . on elaborate neurological survey\nit was found that motor power of the patient s right side upper and lower limb was of grade 0/5 with anesthesia of left side below c3 .\nshe was evaluated with a cervicodorsal mri scan , which showed a hyper intense space occupying lesion suggesting an epidural hematoma at the c3-c4 level ( fig.1 ) .\nthe patient was taken up for emergency surgery . with the patient in prone position under general anaesthesia\n, a posterior midline incision was taken exposing the tips of the spinous processes from c3 to c5 levels .\ntwo bony gutters were drilled bilaterally at the border of the exposed laminae by means of an air drill . in our case ,\nthe left side border of the laminae was excised from its cranial to caudal end with a kerison rongeur and the spinous processes and the laminae were pushed laterally as if to open a door , thereby exposing the spinal canal ( hirabayashi s open door laminoplasty ) .\na. t2 weighted transverse section of the cervical cord showing an area of heterogeneous hyper intensity compressing the cord .\nb. t1 weighted transverse section of the spine showing an isointense lesion compressing the cord . c. t2 weighted sagittal cut of the cervical spinal cord showing heterogeneous hyper intense signal of the hematoma .\npostoperatively the patient was immobilized with a hard cervical collar and physiotherapy ( passive mobilization ) was started .\nfour months following the surgery the patient regained her motor strength to grade 3/5 with partial return of sensory functions . at twelve months follow up motor power of the affected side improved to grade 5/5 with regaining of normal sensory functions on opposite\nabout 40% of the cases reported in the literature till date do not have any demonstrable etiology and are therefore referred to as idiopathic spontaneous cervical epidural hematoma .\nthese need to be differentiated from other well known causes such as neoplasm and systemic diseases , anticoagulant therapy , hypertension or vascular malformations and pregnancy for planning of the management and to predict prognosis .\nthere is controversy regarding the source of the hematoma ; is it arterial or venous ?\nthe proponents of the venous origin theory maintain that the sudden increase in intra - thoracic and intra - abdominal pressure leads to the rupture of the thin walled epidural veins .\nthus during activities like coughing , sneezing , straining during defecation and micturition , vomiting and coitus these thin walled epidural veins may rupture and lead to the generation of the hematoma .\nhowever several authors have pointed out that since the epidural venous pressure is less than the intrathecal pressure , thus these ruptured veins are an unlikely source to produce a hematoma large enough to cause compression of the thecal sac and develope brown sequard syndrome .\nafter study of the arterial structures of the cervical epidural region it has been hypothesized that extreme movements at the cervicodorsal junction could result in tearing of the arteries .\nthe high arterial pressure can lead to development of hematoma large enough to cause compression of the dural sac leading to the clinical syndrome of cord compression .\nthe most common presentation of spontaneous cervical epidural hematoma is acute onset of neck pain , which is usually radiating in nature and the localization depends on the involvement of specific nerve roots .\nthe second most common symptom is weakness of the limbs below the level of compression .\nthe weakness gradually increases over days but complete loss of motor power has not been reported and this deficit rarely recovers spontaneously .\nmri is the diagnostic tool of choice in spontaneous cervical epidural hematoma . on t2 weighted images the hematoma appears as an area of heterogeneous hyper- intensity of the cord with focal hypo - intense areas . on t1 weighted images the lesion is usually iso - intense in the acute phase ; however chronic hematomas may be hyper- intense .\nthe treatment of choice in spontaneous cervical epidural hematoma is emergency surgical decompression although a few cases have been reported in literature to have recovered without any surgical intervention .\nthe procedure of choice is a laminectomy , although a hemi - laminectomy or laminoplasty could be performed depending on the extent and localization of the hematoma .\nispontaneous cervical epidural hematoma leading to a brown sequard syndrome is a rare entity in clinical practice and it has a fatal progressive course in cases where the diagnosis is delayed .\nspontaneous cervical epidural hematoma may present as hemiparesis prompting the emergency room physician to make an erroneous diagnosis of cerebrovascular accident , leading to delay in the diagnosis .\nprompt diagnosis of the condition and urgent decompression is vital to prevent irreversible damage of the cord .\na thorough clinical examination is a must followed by a mri scan of the cervical spine to exclude this rare entity .\nalthough there have been rare reports of spontaneous recovery , surgical decompression is the preferred modality of treatment . in cases presenting as hemiparesis , sensory examination of opposite side\nan mri can delineate the cause and surgical decompression is warrented in cases of spontaneous epidural hematoma that causes neurodeficit .", "answer": "introduction : brown sequard syndrome resulting from compression due to an epidural hematoma is a relatively rare occurrence , more so with a spontaneous history . \n we report one such case.case report : we present a 65yr old female presenting with hemiplegia with contralateral anesthesia . \n magnetic resonance imaging showed a hematoma in the epidural space in the c3-c4 region . \n she underwent an open door laminoplasty for evacuation of the hematoma . following surgery \n the patient responded rapidly and currently at 18 months follow up she is neurologically grade 5/5 with normal sensations.conclusions:in the emergency room when a patient is clinically diagnosed as a case of brown sequard syndrome it is important to ask for an mri scan of the cervical spine . \n hematoma in the cervical epidural space should be considered in the differential diagnosis of brown sequard syndrome especially in the elderly with history of doubtful trivial trauma .", "id": 73} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prostate - specific antigen ( psa ) level has been an important diagnostic tool for detecting prostate cancer .\nit has been shown that an abnormal digital rectal examination ( dre ) has markedly decreased and biochemical findings ( elevated psa ) have increased over the past 20 years for the indication of prostate biopsy .\nthis means that evaluation of prostate cancer is more and more based on the psa level rather than on suspicious dre\n. however , cancer detection rates from biopsy in the presence of isolated psa elevation and a normal dre range between 30% and 40% . also , a high concentration of psa can be found in benign disorders such as benign prostatic hyperplasia ( bph ) , urinary tract infections , and bacterial prostatitis [ 2 - 5 ] .\nalthough it has been reported that acute inflammation is necessary to cause psa elevation , there is growing evidence that subclinical inflammation may also contribute to rises in psa levels [ 6 - 9 ] .\nfurthermore , several investigators have shown that treatment of chronic prostatitis , when identified , can decrease psa , which suggests that the use of anti - microbial or anti - inflammatory drugs may reduce the number of men who need prostate biopsies .\nthere is no doubt that symptomatic prostatitis needs to be treated , but uncertainty exists about the appropriate management of asymptomatic patients with elevated psa and normal dre .\nthe aim of our study was to investigate the possibility of reducing the number of prostate biopsies in patients with a high psa level showing a psa decrease or normalization after antibiotic therapy .\nthis approach could be useful in patients for whom it is necessary to postpone biopsy and in patients with previous negative biopsies who are willing to avoid biopsy until further psa increase .\nthis investigation was conducted prospectively among 413 patients with a serum psa level of over 4 ng / ml to under 10 ng / ml from january 2004 to december 2009 .\nsubjects were excluded if they had been treated by 5-alpha reductase inhibitor for more than 3 months or if they had a history of transurethral resection of the prostate .\nthe psa level was determined by using immunoenzymatic assay before dre and transrectal ultrasonography ( trus ) to avoid false - positive results . to exclude prostatitis\n, all patients underwent the expressed prostatic secretion ( eps ) or voided bladder urine 3 ( vb3 ) test to be classified into two groups .\none group had positive findings on the eps or vb3 test and the other group had negative findings .\na cover slip was placed over the specimen and it was examined under high - power microscopy . a positive finding\nwas defined as a white blood cell ( wbc ) count higher than 10 in the prostate secretion after eps or wbc higher than 10 in vb3 urine after eps .\nthe patients with a positive result were treated with quinolone antibiotics for 2 months , and they were asked to return for repeat screening 2 months later . if the psa level was still higher than 4 ng / ml after 2 months , the patients underwent prostate biopsy . in the other cases , the patients avoided prostate biopsy\nthe subjects underwent at least 10 core biopsies with transrectal ultrasound - guided needle biopsy of the prostate .\nchicago , il , usa ) was used for the statistical analysis , and independent t - tests were used for analysis of the characteristics of both groups .\nof the 413 men studied , 215 ( 52% ) patients had positive findings on the eps or vb3 test .\nof the 215 patients , 53 men avoided prostate biopsy because their serum psa level had decreased to less than 4 ng / ml . the other patients ( 162 of 215 ) still had an elevated serum psa level of more than 4 ng / ml , including 7 in whom the biopsy results revealed cancer .\npatients with negative findings on the eps or vb3 test ( 198 of 413 ) underwent prostate biopsy immediately ( fig .\nthe total prostate cancer detection rate was 11.6% in our subjects , whereas it was 20.7% in the patients with negative findings on the eps or vb3 test and 3.3% in those with positive findings , respectively .\nthe mean age was significantly different between the positive group ( 65.0 ) and the negative group ( 71.2 ) .\nthere were no significant differences in the mean initial serum psa level or prostate volume between the groups ( table 1 ) .\nsince psa was introduced in the 1980s as a variable for detecting prostate cancer , the detection rate of prostate cancer has been increasing .\nit is true that an abnormal finding on a dre or trus is an indication for prostate biopsy , but in the majority of cases , the psa level is the most important factor in deciding whether we will proceed with prostate biopsy .\nhowever , it is reported that 30 to 40% of patients who test positive for prostate cancer in prostate biopsy proceeded when only the psa was increased without any abnormality in the dre or trus .\nthe specificity and sensitivity of psa can result in high values in other positive diseases .\nthe psa may increase not only in bph but also in urinary tract infection and bacterial prostatitis .\nthe psa can increase in acute inflammation and silent infection [ 7 - 9,12 ] .\nalso , some researchers have reported that treatment with antibiotics and anti - inflammatory drugs for chronic prostatitis can decrease the psa and the necessity for prostate biopsy .\nnadler et al . reported that the size and infection of the prostate can be a chief cause of psa increase in the case of patients not diagnosed with prostate cancer .\nbut irani et al . reported that even if there is an infiltration of inflammatory cells in the prostatic interstitium , it is not related to the psa increase in the blood if the glandular epithelial cell layer is not destroyed at the same time .\nfurthermore , it has been reported that the existence of inflammatory cells of the interstitium or glandular tissue in the prostate biopsy has no statistical affiliation with the concentration of psa in the blood .\ncarver et al . argued that national institutes of health ( nih ) category iv asymptomatic prostatitis increases the psa concentration in the blood , but its clinical significance is not that greatbecause the mean differences with the normal group are 2.3 ng / ml and 1.4 ng / ml , respectively .\nreported that there is an increase of the concentration of psa in the blood in 71% of patients with acute prostatitis , 15% of patients with chronic prostatitis , and 6% of patients with nonbacterial prostatitis , but there was no psa increase in patients who showed only symptoms of chronic prostatitis .\nfound a relation of the psa concentration in the blood with acute and chronic prostatitis accompanied by clinical symptoms identified histologically , but no relation in the case of deactivated prostatitis .\nchang et al . investigated 223 patients who tested negative in a prostate biopsy by classifying the infection level and reached the conclusion that the whole size of the prostate is an important factor that contributes to the increase in the psa concentration in the blood , but that there was no relation with the prostatitis level .\nthe relationship of prostatitis and the psa increase continues to stimulate dispute , and we suggest that the findings mentioned above are not sufficient to explain the reason for the psa increase in the case of nih category iv asymptomatic prostatitis .\nnadler et al . investigated 421 patients with nih category iii chronic prostatitis and reported recently that the mean psa concentration in the blood of the patients investigated was 1.97 ng / ml . compared with the level in the normal group of 1.72 ng / ml , this was a statistically significant increase , but it is still below the normal psa range .\nalso , f - psa , percent f - psa , and the [ -2 ] ppsa isoform show some increase with prostate cancer , but they are inappropriate to be used as biomarkers of prostate cancer diagnosis because of their low specificity and sensitivity .\ntreatment with antibiotics in the case of chronic prostatitis and increased psa results in a very significant psa decrease .\nbut any special bacteria is found in 90% of cases of prostatitis with or without symptoms .\nthis kind of investigation of the changes in psa after treatment with antibiotics or anti - inflammatory drugs for nonbacterial prostatitis is uncommon . according to the report of potts among 122 patients with an average psa increase of 9.35 ng / ml , 51 ( 42% ) patients\nwere diagnosed with infection by urinalysis after a massage of the prostate or prostatic secretion ( eps ) .\nthe patients were then treated with antibiotics for 4 weeks , and after 6 to 8 weeks they had a psa examination .\nafter the treatment , 22 of the 51 patients had a normal psa concentration ( average , 2.9 ng / ml ) and they did not need a prostate biopsy .\nbut there was a continuous increase of psa in the remaining 29 patients , and among them , 9 patients were diagnosed with prostate cancer . in comparison with patients diagnosed with cancer in prostate biopsy after treatment with antibiotics ,\nthe psa decrease in patients with benign biopsy results was significantly greater ( -1.3% vs. -21.3% ) . in the investigation carried out with 95 patients diagnosed with nonbacterial prostatitis and who showed an increase of psa , bozeman et al\n. proceeded with prostate biopsy in patients in whom the psa value did not decrease after 4 weeks of treatment with antibiotics and anti - inflammatory drugs . among these ,\nthe psa of 36.4% of patients decreased from 8.48 ng / ml to 5.39 ng / ml after treatment ; in 44 patients ( 46.3% ) the psa decreased below 4 ng / ml , so they avoided prostate biopsy . in the remaining patients who underwent prostate biopsy , 13 patients ( 25.5% )\nwere diagnosed with prostate cancer , 37 patients ( 72.5% ) with chronic infection , and 1 patient ( 1.05% ) with bph . among the patients diagnosed with prostate cancer , just 4.8% of patients had shown a psa decrease from 8.32 ng / ml to 7.92 ng / ml , which was not statistically significant .\ntherefore , the authors argued that chronic prostatitis is the chief cause of psa increase and that treatment for prostatitis can decrease unnecessary prostate biopsy .\nbut hochreiter argued that although the authors of two investigations considered that the patients were not diagnosed with prostate cancer because the psa was decreased to less than 4 ng / ml , it was difficult to conclude that the patients in fact had no cancer .\nit is not a certainty that psa - normalized patients are cancer free after antibiotic therapy .\nthere are no general guidelines that can be applied to all men with increased psa before prostate biopsy . in cases\nin which the psa level is increasing , if we first exclude prostatitis and carry out a serial diagnostic procedure , it may help to reduce unnecessary prostate biopsy .", "answer": "purposewe aimed to reduce unnecessary prostatic biopsy in patients with high prostate - specific antigen ( psa ) by consideration of prostatic inflammation.materials and methodsthe investigation was conducted prospectively in 413 patients with a psa level of 4 to 10 ng / ml from january 2004 to december 2009 . \n all patients underwent the expressed prostatic secretion ( eps ) or voided bladder urine 3 ( vb3 ) test to be classified into two groups : positive group and negative group . \n patients with a positive result on the eps or vb3 test were treated with antibiotics for 2 months , and in cases in which the psa level remained high , we performed prostate biopsy . in patients with a negative result on the vb3 test , we performed prostate biopsy directly.resultsof the 413 study patients , 215 ( 52% ) patients had positive findings on the eps or vb3 test . \n after 8 weeks of antibiotics therapy , 53 of the 215 men avoided prostate biopsy because their psa level was normalized . \n the other patients ( 162 of 215 ) still had elevated psa levels of more than 4 ng / ml , including 7 patients in whom the biopsy revealed cancer . \n patients with negative findings ( 198 of 413 ) underwent prostate biopsy . \n of the 198 patients , 41 were diagnosed with prostate cancer . \n the total prostate cancer detection rate was 11.6% in our subjects , where as it was 20.7% in the patients with negative findings on the eps or vb3 and 3.3% in the patients with positive findings , respectively.conclusionsin cases in which the psa level is increasing , if we first exclude prostatitis and carry out a serial diagnostic procedure , it may help to reduce unnecessary prostatic biopsy .", "id": 74} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngraphene oxide ( go ) solution was synthesized from natural graphite powder by a modification of hummers method.45 cu2o / rgo composites were fabricated by a microwave - assisted hydrothermal reaction .\nfirstly , cu(no3)2 was added to a mixture of ethanol and water in the ratio of 64:36 .\nthen , a calculated amount of go solution and formic acid ( 3 ml ) were added . for optimization , cu2o / rgo composites with different amounts of rgo\nwere also synthesized , which include cu2o/0.25 % rgo , cu2o/0.5 % rgo , and cu2o/1 % rgo , in which x % represents the calculated weight ratio of the go added to cu2o . after stirring for 2 h ,\nthe homogeneous solution was heated with stirring in the microwave system at 150 c for 3 h. after the product was cooled to rt , the final product was collected by centrifugation , washed with water five times , and dried at 70 c .\nblank cu2o was synthesized through the same procedure , except for the addition of go solution .\nxrd was performed by using a rigaku rint 2100 diffractometer at a voltage of 40 kv .\nthe morphologies of the products were characterized by field - emission scanning electron microscopy ( fesem , jeol-6701f ) and tem ( jeol-2010f ) .\nuv / vis spectra were recorded by using a shimadu uv / vis 2550 spectrophotometer .\npl emission spectra were measured at rt by using a fluorescence spectrophotometer ( f-4500 , hitachi ) .\nphotocatalyst ( 5 mg ) and nafion solution ( 10 l , 5 wt % ) were dispersed in a water / isopropanol mixture ( 1 ml , 3:1 v / v ) by at least 30 min sonication to form a homogeneous catalyst colloid . for the measurements ,\nthe catalyst colloid ( 100 l ) was deposited onto an area of approximately 1 cm of the fto conductive glass to form the working electrode .\na pt wire was used as a counter electrode , and an ag / agcl electrode was the reference electrode in the three - electrode photo - electrochemical system .\neis were recorded under an alternating current perturbation signal of 10 mv over the frequency range of 1 mhz to 100 mhz .\nthe potential ranged from 1.0 to 0 v with a potential step of 10 mv at a frequency of 1 khz .\nthe co2 reduction reaction was performed in batches by using a septum - sealed glass chamber with a volume of 120 ml , which was heated at 160 for 1 h prior to measurement . to remove possible trace organic contaminants ,\nphotocatalysts were treated at 200 c for 3 h in a tubular furnace under the protection of ar or in air ( denoted cu2o treated in ar or air ) .\na typical photocatalytic experiment was conducted by using 0.5 g of photocatalysts and 3 ml of deionized water in a co2-purged 120 ml reactor .\nexcess ( 0.7 m ) sodium sulfite was added to each batch as a hole scavenger.15 , 46 a 150 w xe lamp ( newport ) was used as a light source .\nthe light output was measured by using a newport 1918-r high - performance optical power meter fitted with a newport 918-d calibrated photodetector equipped with an integrated attenuator .\nthe reaction product was monitored by periodical sampling of the gas phase from the glass chamber by using a gas - tight syringe and analyzed by gc ( varian gc-450 ) with a thermal conductivity detector ( tcd , connected to a molecular sieve column ) to detect h2 , o2 , and n2 and a flame ionization detector ( fid , connected to a cp - sil 5cb capillary column ) to detect hydrocarbons .\na methanizer was installed to enable the fid to detect co with 1000 higher sensitivity . for the isotope - tracer experiment ,\nafter the addition of cu2o / rgo ( 0.5 g ) into co2-saturated water ( 10 ml ) , the septum - sealed reactor was purged by ar gas for 10 min .\nthe sample was irradiated with a 150 w xe lamp for 30 min , and then 0.5 ml of the reaction product taken from the vessel headspace was analyzed by gc \ngraphene oxide ( go ) solution was synthesized from natural graphite powder by a modification of hummers method.45 cu2o / rgo composites were fabricated by a microwave - assisted hydrothermal reaction .\nfirstly , cu(no3)2 was added to a mixture of ethanol and water in the ratio of 64:36 .\nthen , a calculated amount of go solution and formic acid ( 3 ml ) were added . for optimization , cu2o / rgo composites with different amounts of rgo\nwere also synthesized , which include cu2o/0.25 % rgo , cu2o/0.5 % rgo , and cu2o/1 % rgo , in which x % represents the calculated weight ratio of the go added to cu2o . after stirring for 2 h ,\nthe homogeneous solution was heated with stirring in the microwave system at 150 c for 3 h. after the product was cooled to rt , the final product was collected by centrifugation , washed with water five times , and dried at 70 c .\nblank cu2o was synthesized through the same procedure , except for the addition of go solution .\nxrd was performed by using a rigaku rint 2100 diffractometer at a voltage of 40 kv .\nthe morphologies of the products were characterized by field - emission scanning electron microscopy ( fesem , jeol-6701f ) and tem ( jeol-2010f ) .\nuv / vis spectra were recorded by using a shimadu uv / vis 2550 spectrophotometer .\npl emission spectra were measured at rt by using a fluorescence spectrophotometer ( f-4500 , hitachi ) .\nphotocatalyst ( 5 mg ) and nafion solution ( 10 l , 5 wt % ) were dispersed in a water / isopropanol mixture ( 1 ml , 3:1 v / v ) by at least 30 min sonication to form a homogeneous catalyst colloid . for the measurements ,\nthe catalyst colloid ( 100 l ) was deposited onto an area of approximately 1 cm of the fto conductive glass to form the working electrode .\na pt wire was used as a counter electrode , and an ag / agcl electrode was the reference electrode in the three - electrode photo - electrochemical system .\neis were recorded under an alternating current perturbation signal of 10 mv over the frequency range of 1 mhz to 100 mhz .\nthe potential ranged from 1.0 to 0 v with a potential step of 10 mv at a frequency of 1 khz .\nthe co2 reduction reaction was performed in batches by using a septum - sealed glass chamber with a volume of 120 ml , which was heated at 160 for 1 h prior to measurement . to remove possible trace organic contaminants ,\nphotocatalysts were treated at 200 c for 3 h in a tubular furnace under the protection of ar or in air ( denoted cu2o treated in ar or air ) .\na typical photocatalytic experiment was conducted by using 0.5 g of photocatalysts and 3 ml of deionized water in a co2-purged 120 ml reactor .\nexcess ( 0.7 m ) sodium sulfite was added to each batch as a hole scavenger.15 , 46 a 150 w xe lamp ( newport ) was used as a light source .\nthe light output was measured by using a newport 1918-r high - performance optical power meter fitted with a newport 918-d calibrated photodetector equipped with an integrated attenuator .\nthe reaction product was monitored by periodical sampling of the gas phase from the glass chamber by using a gas - tight syringe and analyzed by gc ( varian gc-450 ) with a thermal conductivity detector ( tcd , connected to a molecular sieve column ) to detect h2 , o2 , and n2 and a flame ionization detector ( fid , connected to a cp - sil 5cb capillary column ) to detect hydrocarbons .\na methanizer was installed to enable the fid to detect co with 1000 higher sensitivity .\nafter the addition of cu2o / rgo ( 0.5 g ) into co2-saturated water ( 10 ml ) , the septum - sealed reactor was purged by ar gas for 10 min .\nthe sample was irradiated with a 150 w xe lamp for 30 min , and then 0.5 ml of the reaction product taken from the vessel headspace was analyzed by gc \nas a service to our authors and readers , this journal provides supporting information supplied by the authors .\nsuch materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors", "answer": "a facile one - step microwave - assisted chemical method has been successfully used for the synthesis of cu2o / reduced graphene oxide ( rgo ) composites . \n photocatalytic co2 reduction was then investigated on the junction under ambient conditions . \n the rgo coating dramatically increases cu2o activity for co2 photoreduction to result in a nearly six times higher activity than the optimized cu2o and 50 times higher activity than the cu2o / ruox junction in the 20th hour . \n furthermore , an apparent initial quantum yield of approximately 0.34 % at 400 nm has been achieved by the cu2o / rgo junction for co2 photoreduction . \n the photocurrent of the junction is nearly double that of the blank cu2o photocathode . \n the improved activity together with the enhanced stability of cu2o is attributed to the efficient charge separation and transfer to rgo as well as the protection function of rgo , which was proved by xrd , sem , tem , x - ray photoelectron spectroscopy , photo - electrochemical , photoluminescence , and impedance characterizations . \n this study further presents useful information for other photocatalyst modification for efficient co2 reduction without the need for a noble - metal co - catalyst .", "id": 75} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndue to the widespread use of imaging modalities , such as ultrasonography , computed tomography ( ct ) , and magnetic resonance imaging , the incidences of incidentally found small cortical renal masses ( srms ) and renal cell carcinoma ( rcc ) , have increased during the past years . for decades , the standard therapy for patients with clinically suspected rcc consisted of radical nephrectomy , an invasive surgical procedure with high morbidity .\nhowever , in a recently published randomized trial of nephron - sparing surgery ( nss ) in patients with srm yielded comparable oncological outcome with radical nephrectomy . in addition\n, population - based studies clearly demonstrate an overall survival benefit in patients undergoing nss as a result of preserved renal function [ 4 , 5 ] .\nnephron - preserving procedures , such as partial nephrectomy and image - guided minimally invasive ablative procedures , have therefore increasingly been applied in patients with srm [ 6 , 7 ] .\ninitially , image - guided ablative procedures were performed in patients who were not suitable candidates for nss based on significant medical comorbidity , advanced symptomatic disease , or refusal of conventional therapy [ 6 , 8 ] .\naccumulating data on follow - up and oncological safety suggest a broader indication in patients with srm .\na particular form of an image - guided ablative procedure is radiofrequency ablation ( rfa ) , which can be performed open or percutaneously . in rfa , an electric current oscillates through an electrode placed centrally in the target tissue .\nthis results in frictional ionic agitation and heat formation in the tissue surrounding the tip of the electrode , causing local protein coagulation and cellular death . compared with open and laparoscopic ( partial ) nephrectomy\nit is a nephron - sparing therapy with low morbidity and mortality , short hospital stay , and acceptable oncologic outcome [ 8 , 10 , 12 ] .\nnevertheless , rfa of the kidney can be accompanied by minor and even major complications .\nseveral investigators have postulated the occurrence of bowel perforation as a complication of rfa of renal masses due to the close proximity of bowel [ 13 , 14 ] . to our current knowledge ,\nonly two articles have described such a case [ 15 , 16 ] . yet in a large series of 100 percutaneously performed renal rfas , none of the patients had colonic injuries .\nthe reported incidence of bowel perforation complicating renal rfa therefore ranges from 0 to 8.3% [ 8 , 15 ] . in this article\n, we describe the first case of appendiceal perforation as a complication of ct - guided percutaneous rfa of an smr .\na 60-year - old male patient was referred to our outpatient clinic with an incidental mass in the right kidney , which was recently diagnosed during work - up of his microscopic hematuria .\nhis previous medical history consisted of kidney stone lithotripsy , hypertension treated with a beta - blocker and diuretic , and two episodes of transient ischemic attack .\nabdominal ct scan showed a rapidly enhancing , exophytic mass in the lower pole of the right kidney with a maximum diameter of 2.5 cm ( fig . \nthe appendix was noticed in a retrocecal position , at a 1.4-cm distance from the renal mass ( fig . \n1b , c ) . based on his mild comorbidity and on the small size of the renal mass ,\n1a small , exophytic , rapidly enhancing renal mass at the lower pole of the right kidney .\nb retrocecal position of the appendix on the lateral site of the right kidney in the vicinity of the renal mass ( c ) .\n* appendix , renal mass a small , exophytic , rapidly enhancing renal mass at the lower pole of the right kidney .\nb retrocecal position of the appendix on the lateral site of the right kidney in the vicinity of the renal mass ( c ) .\n* appendix , renal mass our technique of rfa in renal masses has extensively been described in previous articles [ 17 , 18 ] . in short ,\nafter the patient received an antibiotic prophylaxis ( 1,500 mg cefuroxim ) and epidural analgesic before the rfa procedure , he was placed in prone position on the ct table .\na planning ct scan was performed to locate the renal mass . under fluoroscopic ct guidance ,\na 17 g cool - tip electrode ( valleylab , covidien , boulder , co ) was placed centrally into the mass .\nsubsequently a 20 g needle was inserted lateral in the anterior pararenal space for injection of dextrose in water to hydrodissect the renal mass from the surrounding vital tissues , such as the colon and appendix . after the hydrodissection and\nthe positions of the needles were checked with a ct scan of the area of interest , ablation was started .\nfinal temperature after 15 min was > 75c with adequate roll - offs .\nthe rfa procedure was performed by a highly experienced interventional radiologist ( w.p . ) who at that time had already performed > 180 percutaneous image - guided ablative procedures ( including renal , liver , and lung ) .\na 60-year - old male patient was referred to our outpatient clinic with an incidental mass in the right kidney , which was recently diagnosed during work - up of his microscopic hematuria .\nhis previous medical history consisted of kidney stone lithotripsy , hypertension treated with a beta - blocker and diuretic , and two episodes of transient ischemic attack .\nabdominal ct scan showed a rapidly enhancing , exophytic mass in the lower pole of the right kidney with a maximum diameter of 2.5 cm ( fig . \nthe appendix was noticed in a retrocecal position , at a 1.4-cm distance from the renal mass ( fig . \n1b , c ) . based on his mild comorbidity and on the small size of the renal mass ,\n1a small , exophytic , rapidly enhancing renal mass at the lower pole of the right kidney .\nb retrocecal position of the appendix on the lateral site of the right kidney in the vicinity of the renal mass ( c ) .\n* appendix , renal mass a small , exophytic , rapidly enhancing renal mass at the lower pole of the right kidney .\nb retrocecal position of the appendix on the lateral site of the right kidney in the vicinity of the renal mass ( c ) .\nour technique of rfa in renal masses has extensively been described in previous articles [ 17 , 18 ] . in short ,\nafter the patient received an antibiotic prophylaxis ( 1,500 mg cefuroxim ) and epidural analgesic before the rfa procedure , he was placed in prone position on the ct table .\na planning ct scan was performed to locate the renal mass . under fluoroscopic ct guidance ,\na 17 g cool - tip electrode ( valleylab , covidien , boulder , co ) was placed centrally into the mass .\nsubsequently a 20 g needle was inserted lateral in the anterior pararenal space for injection of dextrose in water to hydrodissect the renal mass from the surrounding vital tissues , such as the colon and appendix .\nafter the hydrodissection and the positions of the needles were checked with a ct scan of the area of interest , ablation was started .\nfinal temperature after 15 min was > 75c with adequate roll - offs .\nthe rfa procedure was performed by a highly experienced interventional radiologist ( w.p . ) who at that time had already performed > 180 percutaneous image - guided ablative procedures ( including renal , liver , and lung ) .\non the ct images performed during the procedure , the colon and appendix were considered to be a safe distance ( at least 1.0 cm ) from the ablative field as a result of the hydrodissection ( fig . 2 ) .\nadequate ablation of the kidney tumor was achieved without intraprocedural complications . on the first postprocedural day\nfluid collection with air configuration on the lateral and anterior side of the renal mass as a result of hydrodissection can be seen .\nretrocecal appendix ( * ) is in the vicinity of the ablative field patient in left lateral decubitus position during rfa procedure .\nfluid collection with air configuration on the lateral and anterior side of the renal mass as a result of hydrodissection can be seen .\nretrocecal appendix ( * ) is in the vicinity of the ablative field five days after the procedure , he presented at our hospital with fever ( 39.5c ) and right lumbar pain .\n3 ) showed a large retroperitoneal fluid collection with air configurations , suggesting retroperitoneal abscess formation , on the lateral side of the right kidney .\nmoreover , a direct connection was noticed between the cecum and fluid collection , with contrast material in the retroperitoneal abscess , suggesting perforation at the base of the appendix ( fig . 3 ) .\nafter ct - guided drainage of the abscess and intravenous antibiotic therapy , the patient remained septic . therefore , 2 days later laparotomy was performed .\nintraoperatively , a retroperitoneally confined abscess was drained . however , due to an extensive local inflammatory reaction affecting the terminal ileum ( fig . \n4 ) , the approach had to be extended intra - abdominally to allow necessary resection of the ileocecal region followed by primary anastomosis between the ileum and ascending colon and an omental plasty . during this step ,\nhistopathologic examination of the resected specimen showed a perforated appendix based on ulcero - phlegmonous and gangrenous inflammation . on day 18 after the rfa\n3leakage of contrast material from the perforated cecum / appendiceal base into the right anterior pararenal space suggesting appendiceal perforation . presence of air configurations in the right anterior pararenal space suggesting abscess formationfig . \noversewn cecal perforation at the base of the necrotic appendix leakage of contrast material from the perforated cecum / appendiceal base into the right anterior pararenal space suggesting appendiceal perforation .\npresence of air configurations in the right anterior pararenal space suggesting abscess formation intraoperative view after abscess drainage .\nrfa of srm was first applied in 1997 and has proven to be a promising and safe technique since . in a large series of 100 patients with renal tumors treated with rfa , 11 minor and major complications were reported , of which the most common was haemorrhage .\n. complications of rfa can generally be divided into two categories : ( 1 ) those related to imaging - guided electrode placement and ( 2 ) those related to thermal therapy .\nthe latter are more common in kidney rfa compared with other rfa indications , e.g. , hepatic rfa , as a result of the proximity of other vital structures , such as the bowel and ureter . nevertheless , only two articles so far have reported bowel perforation as a complication of renal rfa [ 15 , 16 ] .\nthe first step in preventing thermal complications is thorough assessment of the tumor location on preprocedural ct scans during the process of patient selection .\npercutaneous renal rfa can be performed with the patient prone or in lateral decubitus position . in both positions ,\nvital structures in the vicinity of the target mass will be kept away from the ablative zone by way of gravity .\nthird , the rfa electrodes can be used to lift the ablated tumor away from vital structures .\nexamples of invasive methods include hydrodissection with glucose in water or injection of carbon dioxide in between the target tissue and the tissue that needs protection . in our patient ,\na lateral dissection was performed with glucose in water to dissect the renal mass from the appendix and the colon , which was located caudolateral with respect to the renal mass .\nunfortunately , in this way the appendix came even closer to the tract of the needle .\nnevertheless , on the ct images performed during the procedure , the appendix was considered to be at sufficient distance from the ablative field .\neventually , this caused the appendiceal perforation . since this complication , we modified our ablative technique .\ncurrently we start the hydrodissection before placement of the rfa electrode in the target tissue . in addition , instead of injecting 100 cm fluid during hydrodissection , we attach the needle to a continuous drip system .\nin conclusion , in this article we described a case of appendiceal perforation leading to retroperitoneal abscess formation as a complication of percutaneous rfa of an srm .\nalthough rfa of srm is generally a minimally invasive and safe procedure , one should be aware of the possibility of particular minor and major complications when performing this innovative and promising procedure .\nif vital structures remain in close vicinity of the ablative field , one should consider treatment options other than rfa .", "answer": "percutaneous radiofrequency ablation ( rfa ) has gained wide acceptance as nephron - sparing therapy for small renal masses in select patients . generally , it is a safe procedure with minor morbidity and acceptable short - term oncologic outcome . \n however , as a result of the close proximity of vital structures , such as the bowel , ureter , and large vessels , to the ablative field , complications regarding these structures may occur . \n this is the first article describing appendiceal perforation as a complication of computed tomography - guided rfa despite hydrodissection . when performing this innovative and promising procedure one should be aware of the possibility of particular minor and even major complications \n .", "id": 76} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneoadjuvant chemotherapy actually takes an important place in treatment of operable breast cancer in the hope of improving conservative surgery rate of female patients .\nneoadjuvant chemotherapy includes today on target therapies involving the research on expression of specific molecules by tumoral cells . in routine practice , estrogen receptors ( er )\n, progesterone receptors ( pr ) , and human epidermal growth factor receptor 2 ( her2 ) are the common used biomarkers .\nnew pharmaceutical molecules , other than er / pr or her2 , are now already evaluated in clinical research as new biomarkers and new target for neoadjuvant therapy .\nfine - needle aspiration cytology ( fnac ) of the breast is wellknown as a safe , effective , economical , and accurate technique for diagnosing palpable breast lesion [ 24 ] .\nthis last decade , fnac technique is improved by the development of new cytological methods allowing standardization of fixation and assuring constant results with ancillary tests such as immunocytochemistry and in situ molecular biology .\nalso , one of the advantages of fnac is the management of small tissue fragments permitting a repetitive evaluation of the chronological evolution in expression of tumoral biomarkers .\npreviously , the role of fnac has been challenged by results obtained with cnb that seems more robust than fnac . in general ,\nnevertheless , cnb carries disadvantage in terms of a long tissue processing time and patient discomfort such as pain ( 1.7% to 3.7% ) , hematoma ( 0.72% ) , and very rarely pneumothorax [ 6 , 7 ] .\nfnac includes more advantages than cnb such as minimal invasiveness and minimal discomfort ( more painless ) that could be interesting for aged or frailty patients with comorbidities . in palpable lesions ,\nfnac could perform repetitively and is a serious candidate for the chronological followup of neoadjuvant chemotherapy response .\nan important quality of fnac is its ability to give rapid diagnostic information equivalent to that of frozen sections . in our experience\n, the result of rapid fnac prior to cnb improves the quality of cnb and gives an immediate diagnosis decreasing anxiety of patient . \nother indications of fnac are staging of multiple tumors or suspicious zones and apparition of a new suspicious lesion during neoadjuvant chemotherapy .\nfinally , fnac could be an excellent alternative when radiographic screening of breast is not available . \ntable 1 compares the main advantages and disadvantages of fnac versus cnb . \n other clinical fnac indications . \n\npalpable breast lesion.rapid diagnosis to decrease anxiety of patient.patient with morbidity ( senile , cardiac , diabetic etc.).clinical staging : multiple lesions , suspicious lymph node , and so on .\napparition of new lesion in patient treated for breast cancer.evaluation of biomarkers.evaluation of biomarker changes following time or metastasis . when cnb technique is not available . \n \nevaluation of biomarker changes following time or metastasis . when cnb technique is not available .\nit is well known that the combination of clinical evaluation , mammography , and fnac , called triple diagnosis , gives a precise diagnosis [ 10 , 11 ] .\nyu et al . recently demonstrated in meta - analysis of 46 studies that fnac had a sensitivity of 92.7% and a specificity of 94.8% except the unsatisfactory samples .\nthe roc curve showed an excellent area under the curve of 0.986 , presenting a high level of accuracy . on the other hand ,\nif the fnac result was negative , the probability of breast cancer is approximately 8% .\nthese authors concluded that fnac was an accurate material for evaluation on breast malignancy if rigorous criteria are used .\nalso , they said that fnac may provide a favourable screening method and permit an improvement of treatment planning .\ntherefore , when fnac is unsatisfactory , cnb is required to minimize the probability of a missed malignant diagnosis . in a study of fnac and immediate diagnosis performed in 408 palpable breast lesions , liew et al . in 2010 \nreached the same conclusions : 98.1% sensitivity , 89.5% specificity , and 95.8% accuracy . in 508 cnb followed by jackman et al .\n, the rate of false negative for all lesions was 4.4% , for microcalcifications alone 1.2% , and for tumoral mass 0.8% .\nthese results of cnb are quasi - identical to those obtained with the satisfactory fnac .\nmost of false negative fnac results of sampling error or discordance between clinical and histological observations [ 6 , 14 ] . in a comparison between cnb and repeat fnac after an indeterminate diagnosis with fnac , kooistra et al . \nsuggested that cnb should be performed after an indeterminate fnac to obtain a reliable preoperative diagnosis .\nother authors concluded that , although the fnac is easier to perform , this technique was not efficient for small and nonpalpable lesions or diagnosis of microcalcifications as those for in situ carcinoma .\nthese comments are likely true because some preneoplastic lesions are associated with slight cell atypia .\nhowever , bilous emphasized that cnb shows also problems with similar lesions such as atypical proliferative lesions ( atypical ductal hyperplasia , in situ lobular neoplasia , etc . ) , cellular fibroepithelial lesions , papillary tumors , mucinous carcinoma , radial scar , spindle cell lesions .\nmoreover , fnac interpretation requires serious experience of the cytopathologist and they think that this is one of the main reasons that overall cnb is to be preferred . a recent japanese study of 5693 fnac and 7 different laboratories illustrated a great variability between the institutions suggesting likely difference between education of cytologists and the lack of clinical or radiological information ( triple diagnosis ) .\nthese last years a new cytological technique , called liquid - based cytology ( lbc ) , has been developed and approved by the food and drug administration .\nbriefly , lbc standardises the cell fixation , concentrates epithelial cells , and discards blood cells and/or cell debris that obscure the smear .\nthe efficiency of lbc in the breast cytology has been demonstrated by numerous publications . \nthe main advantage of lbc is surely to adjunct ancillary tests such as immunocytochemistry , flow cytometry , or molecular biology [ 1820 ] .\ncompared the er and pr statuses from fnac ( immunocytochemistry ) and cnb ( immunohistochemistry ) , both performed on surgical breast tumors .\nthey found that both methods give similar results with a concordance between the 2 tests of 98% for er ( with kappa correlation score = 0.93 ) and 96% for pr ( kappa = 0.91 ) .\n. demonstrated similar data in a comparative study between primary breast tumours and their metastasis .\ninterestingly , the concordance between these both localisations was 81% for er , 65% for pr , and 71% for her2 , suggesting a possibility of biological difference between primary tumors and their metastasis . \nother publications showed a long - time storage at 20c and 80c at least 6 months without significant loss of immunoreactivity of pr and ep from breast fnac .\nthe cell block cytology is an attractive cytological method for ancillary techniques or long - time cell conservations and consists in putting cells of fnac directly in formol fixative fluid identically at a classical histology ( figures 1 and 2 : er , her2 and fish on cell block cytology ) . briefly , after centrifugation to concentrate cells , the pellet was embedded in a synthetic polymer gel that is then processed in paraffin block that could be cut at 4 m , as classical biopsy slides . with this technique , ferguson et al . \nfound a concordance rate of 95% for er , 90% for pr , and 88% for her2 .\nsimilar results were observed by shabaik et al . with high specificity ( 100% for both ) and lower sensibility ( 85% and 80% resp .\nfor er and pr ) . finally , in fnac , false negative er or pr immunostaining exists but false positive tests are very unlikely .\nfalse negative immunohistochemical results are also observed in cnb : in a retrospective study , seferina et al . \ncalculated a rate of false negative of 26.5% and a rate of false positive of 63.8% for both er and pr . for her2 , they showed 5.4% for false negative rate and 50% for false positive rate .\nnevertheless , in our experience , this discordance is often associated with the manipulation of cnb before the fixation ( crush artefacts ) or with a defect of fixation as desiccation .\nfortunately the concordance with molecular biology by hybridisation in situ using fish , cish , and sish is very good and can help when her2 is uncertain [ 6 , 25 , 27 ] .\nthe fish is accurate for lbc cytology [ 22 , 25 , 28 , 29 ] .\nthe extraction of mrna or dna is also feasible from lbc and fnac , allowing all gene expression analyses [ 2932 ] . in our experience ,\nthe clinical staging and preoperative lymph node status are important for the evaluation of eligible patient to neoadjuvant therapy . in the axillary lymph node fnac , chang et al . \nfnac in lymph node is a cost effective and safe method , false positive is virtually non - existent , and false negative can occur when lymph node is partially involved such as by micrometastase , or isolated tumor cells . in our experience\n, we improve axillary lymph node fnac / lbc by immunocytochemistry using cytokeratin antibody . \nthus , axillary fnac plays a role in staging of advanced cases for systemic and neoadjuvant therapy and in evaluating candidates for sentinel lymph node surgical procedure or axillary lymph node dissection .\ndespite the fact that cnb has been progressively replaced by fnac in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion , fnac has yet a role in palpable lesions in the triple diagnosis association and performed by experienced cytologists . in these conditions , fnac is a safe , effective , economical , and accurate technique for breast cancer evaluation . \nrecently , cytological methods using lbc technology , associated or not with the cellblock cytological technique , improve immunocytological and molecular tests with the same efficiency as classical histology . \nif the limits of its indications are well known , fnac still plays a role in the modern oncological practice .", "answer": "despite the fact that cnb has been progressively replaced by fnac in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion , fnac has yet a role in palpable lesions provided it is associated with the triple diagnosis and experienced cytologist . in these conditions \n , fnac is a safe , effective , economical , and accurate technique for breast cancer evaluation . \n numerous literature reviews and meta - analyses illustrated the advantages and disadvantages of both methods cnb and fnac . \n the difference does not seem significant when noninformative and unsatisfactory fnac was excluded . \n recently , cytological methods using liquid - based cytology ( lbc ) technology improve immunocytological and molecular tests with the same efficiency as classical immunohistochemistry . \n \n the indications of fnac were , for palpable lesions , relative contraindication of cnb ( elderly or frailty ) , staging of multiple nodules in conjunction or not with cnb , staging of lymph node status , newly appearing lesion in patient under neoadjuvant treatment , decreasing of anxiety with a rapid diagnosis , evaluation of biomarkers and new biomarkers , and chronological evaluation of biomarker following the neoadjuvant therapy response .", "id": 77} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients who present to the emergency department with chest pain require rapid triage , evaluation and management .\nmyocardial infarction with st segment elevation ( ste ) on electrocardiography ( ecg ) is a common presentation in emergency rooms across the world .\nacute coronary syndrome ( acs ) marked by ste on the ecg warrants consideration for emergent cardiac catheterization and possible percutaneous coronary intervention ( pci ) .\nin fact , there are now core measures and quality metrics in place that grade a hospital 's efficiency at caring for such patients .\nhowever , the time pressure to optimize such quality metrics may lead to an unintended rush to treatment prior to adequate evaluation . in this report\n, we present a rare case where myocardial infarction was seen as a presenting feature of an underlying hematologic disease , thrombotic thrombocytopenic purpura ( ttp ) .\nthis case highlights the importance of a thorough , yet efficient , clinical evaluation in which the history , physical exam , ecg and laboratory data were needed to make the appropriate triage decision and not miss an unusual diagnosis .\na 48-year - old woman with no known coronary risk factors was transferred from an outside facility to the cardiac catheterization laboratory of our hospital with the diagnosis of ste myocardial infarction for primary pci .\non arrival to our catheterization laboratory , the ecg from the referring hospital showed sinus tachycardia with normal axis and intervals .\nthere was ste in leads i , ii , avl , v46 and reciprocal st segment depression in lead iii [ figure 1 ] .\nlaboratory data were not yet available . however , the patient 's history of present illness was significant for malaise , fever , chills and lethargy that began 3 days prior to hospitalization . further questioning\nestablished that she had mild generalized abdominal pain and one episode of non - bloody diarrhea .\nthe family also noted that she had been intermittently confused and was talking gibberish . on the morning of admission\n, she had severe chest pain associated with nausea , vomiting and dyspnea on exertion , which led her to seek medical care .\nsinus tachycardia at 121 beats per minute with st segment elevation in lead i , ii , avl , v46 on examination , she appeared toxic and in respiratory distress .\nvital signs revealed a blood pressure of 126/70 mmhg with a heart rate of 121 beats per minute .\nin addition , mottling of her skin and livedo reticularis over the thighs was noted .\nthere were a few purpuric skin lesions observed in her antecubital fossa and upper arms .\nher jugular venous pressure was elevated up to the angle of the jaw . cardiac exam revealed a normal first and second heart sound along with a fourth heart sound .\nperipheral pulses were not palpable in the feet and were only faintly palpable in the arms .\nneurologically , she was somewhat confused , but the sensory and motor exam was essentially normal . given that the patient was not having active chest pain , the history was inconsistent with acs and she appeared more toxic than expected for a lateral wall myocardial infarction ; cardiac catheterization was deferred and emergent laboratory studies were obtained .\ninitial laboratory studies revealed a white blood cell count of 13.5 10/mm ; hematocrit of 24% ; mean corpuscular volume of 88.4 fl and platelet count of 6 10/l .\nher lactate dehydrogenase was elevated at 2820 units / l and haptoglobin was low at less than 10 mg / dl .\ncoagulation profile showed international normalized ratio of 1.2 , prothrombin time of 12.6 seconds , fibrinogen 199 mg/ l and d - dimer 1.27 feu\nelectrolytes were within normal limits ; acute kidney injury was noted with blood urea nitrogen 51 mg/ dl and creatinine 1.9 mg / dl .\ntotal bilirubin was markedly elevated at 32 mg% with an indirect bilirubin of 2.1 mg% .\ncardiac biomarkers were elevated with creatinine kinase of 487 units / l and mb fraction of 28.8 ng / ml . troponin - t was 0.86 ng / ml . urinalysis showed ph of 6.0 , 3 + albumin , 3 + hemoglobin , eight wbcs and greater than two rbcs with some amorphous crystals .\nechocardiography demonstrated an ejection fraction of 4045% with severe hypokinesis of the inferior and basal anteroseptal wall .\nno significant valvular lesions were noted . in view of the acute onset of symptoms associated with microangiopathic hemolytic anemia , thrombocytopenia ,\nacute kidney injury and waxing and waning mental status , the presumptive diagnosis of ttp was made .\na disintegrin and metalloproteinase with thrombospondin motifs ( adamst-13 ) activity was found to be low with presence of adamst-13 inhibitors in the plasma .\nshe improved clinically with this treatment and normalized her platelets and lactate dehydrogenase , and ste in her ecg resolved [ figure 2 ] .\noutpatient cardiovascular follow - up demonstrated normalization of the left ventricular ejection fraction by echocardiography and a completely normal nuclear myocardial perfusion stress study .\nfurther testing with invasive catheterization was not pursued as the entire episode was considered to be transient , secondary to metabolic derangement .\nttp is defined as a severe , thrombotic microangiopathy that is characterized primarily by systemic platelet - von willebrand factor aggregation , organ ischemia , profound thrombocytopenia and fragmentation of erythrocytes .\npathologically , focal areas of necrosis and hemorrhage may be seen in the pancreas , adrenals , heart , brain and kidneys.[35 ] although myocardial injury and necrosis are observed in a large number of patients with ttp , it is infrequently the initial presentation , and most likely thought to be due to microthrombi from massive platelet aggregation than plaque rupture thrombosis cascade .\nvarious studies have determined the incidence of myocardial infarction in ttp to range from 1541%.[69 ] however , the heart is one of the most frequently involved organs at autopsy examination of patients with ttp .\nmortality is considerably higher in patients with ttp who have positive cardiac biomarkers , necessitating closer monitoring in this subgroup .\nearly recognition of myocardial injury in a case of ttp is crucial as it identifies higher risk .\nhowever , invasive therapy in the form of cardiac catheterization and pci may be fraught with complications and is precluded by acute kidney injury and low platelet count .\nthrombocytopenia also prevents the use of usual medical management in acs such as antiplatelet and anticoagulant therapy .\nbeta blockers and hmg coa reductase inhibitors may be used although their role is questionable . in acute bouts of ttp , such as this case , the treatment of choice is rapid initiation of plasmapheresis .\nin addition , immunosuppressive therapy including steroid therapy is helpful , especially in the setting of auto - antibodies against adamst-13 factor . relapsing\ncases of ttp have been treated with rituximab , a monoclonal antibody against cd20 on memory b cells with good effect .\nalthough cardiac involvement is common in ttp , as an index event it can be misleading . as swift protocols are activated in the emergency room and catheterization laboratories to ensure quality control , it is equally important to integrate all aspects of patient 's clinical and objective data to detect unusual disease entities", "answer": "myocardial infarction with st segment elevation ( ste ) on electrocardiography ( ecg ) is a common presentation in emergency rooms across the world . \n myocardial injury and necrosis are infrequently the initial presentation in patients with thrombotic thrombocytopenic purpura ( ttp ) . a 48-year - old woman presented with ste myocardial infarction from outside hospital for primary percutaneous coronary intervention . \n however , her clinical picture was not consistent . \n rapid evaluation revealed symptoms associated with microangiopathic hemolytic anemia , thrombocytopenia , acute kidney injury with waxing and waning mental status . \n a diagnosis of ttp was made with low adamst-13 activity . \n plasmapheresis was initiated along with intravenous steroid therapy . \n the patient had a full recovery and went home after full recovery of left ventricular ejection fraction and normal myocardial perfusion studies . \n rapid evaluation is needed to identify infrequent causes of ste myocardial infarction . as swift protocols are activated in the emergency room and catheterization laboratories to ensure quality control , \n it is equally important to integrate all aspects of the patient 's clinical and objective data to detect unusual disease entities .", "id": 78} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrussell body duodenitis ( rbd ) is a rare inflammatory disease characterized by an abundance of polyclonal plasma cells present in the duodenal mucosa .\nthese plasma cells contain intracytoplasmic eosinophilic globules of condensed immunoglobulin , the so - called russell body .\nwe describe the case of a patient with rbd in whom endoscopic and histopathologic findings were observed chronologically , along with a review of the relevant literature .\nhe was found to have a nodule in the right middle lung field on a plain chest radiograph at a local clinic , and was referred to our hospital for detailed examination .\na nodule measuring 2 cm was detected in segment 8 of the right lung on chest plain computed tomography ( ct ) .\nthe morphology of the nodule was lobulated , and cavitation was observed in the interior .\nresults of smear , culture , and polymerase chain reaction assay from sputum specimens were all negative for tuberculosis .\nbronchoscopy was performed on hospital day 9 , during which bronchial lavage fluid was collected , and a biopsy of the nodule was performed .\ndouble capsule - like circular objects were positive for periodic acid - schiff stain and grocott stain , yielding a diagnosis of pulmonary cryptococcosis .\nmoreover , the level of the cluster of differentiation ( cd ) 4 was 570/l , the cd8 level was 655/l , and the cd4/cd8 ratio was 0.87 , suggesting no evidence of aids . on hospital\nesophagogastroduodenoscopy ( egd ; day 14 ) revealed a significant amount of residue and an irregular ulceration with surrounding elevation of the duodenal bulb ( fig .\n1a ) , which had brought about severe stenosis . with the suspicion of duodenal cancer , biopsy samples were obtained from ulcer edges .\nalthough admixed with various inflammatory cells , necrotic tissues were observed , but no definition of adenocarcinoma cells was found ( fig .\nhowever , since some large atypical cells were admixed with infiltrating inflammatory cells , reexamination was required to rule out undifferentiated carcinoma and malignant lymphoma .\nthe second egd ( day 21 ) and the third egd ( day 30 ) revealed no signs of ulcer healing .\ncontrast - enhanced upper gastrointestinal radiography ( day 37 ) revealed severe stenosis from the duodenal bulb to the superior duodenal angle ( fig .\n2 ) . positron emission tomography - ct was performed to screen the whole body for malignant tumors .\nno significant accumulation of fluorodeoxyglucose was observed in any site except the lesion of pulmonary cryptococcosis in the right lung , and no accumulation was detected in the duodenal bulb .\nconsidering this benign stenosis , we performed a gastrojejunostomy ( day 43 ) , and thereafter , oral intake became possible .\nthe fourth egd ( day 56 ) revealed that the peripheral redness and edema of the ulcers had become more severe than in the previous findings ( fig .\nbiopsy samples revealed dissemination of large cells with eosinophilic cytoplasms and eccentric nuclei in the necrotic / granulation tissue of the duodenal lamina propria ( fig .\n3b ) . the large cells were cd20( ) , cd68( ) , cd79a(+ ) , and s100( ) , and they were chain(+ ) or chain(+ ) , suggesting russell bodies derived from polyclonal plasma cells ( fig .\nthe fifth egd ( day 91 ) revealed that the ulcers in the duodenal bulb had reduced in size , and some scarring was present ( fig .\nalthough a biopsy at this time confirmed the presence of a few russell bodies , the majority had disappeared ( fig .\nthe patient is being followed up while continuing the oral administration of a proton pump inhibitor ( ppi ) .\nhsu et al . showed that russell bodies originate from distended rough endoplasmic reticulum in which immunoglobulin is inhibited from being secreted and condensed .\ntazawa and tsutsumi first reported russell body gastritis ( rbg ) in 1998 , in which russell bodies were found in many plasma cells infiltrating the gastric mucosa .\nfirst reported in a patient positive for hiv ; only five cases have since been reported [ 5 - 8 ] .\nthe differential diagnoses include plasmacytoma , mucosa - associated lymphoid tissue lymphoma , and signet ring cell carcinoma . in the present case , because the russell bodies were derived from plasma cells positive for cd79a and were suggested to be polyclonal by the mixture of and chain - positive cells , rbd was diagnosed .\nmany patients with rbg are positive for h. pylori , which is believed to be associated with the development of rbg .\nhowever , only one of the five previously reported cases of rbd was positive for h. pylori .\nthe other background diseases were hiv infection in one , crohn disease in one , retroperitoneal metastasis of ureteral cancer in one , and adenocarcinoma of the ascending colon in one case .\nalthough the development of russell bodies is assumed to be associated with chronic inflammation , microorganisms , and immunodeficiency , the causes of their development remain unknown .\nalthough russell bodies are frequently found in benign tissue adjacent to a malignant tumor , there are also reports suggesting that the production of chemokines in tumor cells is associated with the development of russell bodies . in the present case ,\nthe patient was negative for h. pylori and hiv , and there was no evidence of malignancy or immunodeficiency .\nwe could chronologically observe the endoscopic appearance and histopathological findings of rbd in our patient .\nwhen the ulcers were first detected , although severe infiltration of inflammatory cells was observed , rbd was not manifested . through the aggravation of the ulcers\nfurthermore , the fifth egd revealed a tendency for the ulcers to heal , and the majority of the russell bodies had disappeared . from these processes , it was assumed that the russell bodies were not a cause of the ulcerations , but byproducts secondarily induced by a severe inflammatory state after the development of the ulcers . in the present case , because food residues were always retained in the duodenal bulb , mechanical stimulation might also have been associated with the development of the russell bodies .\nregarding therapeutic responses of russell bodies , there is a report of patients with rbg who were positive for h. pylori , in whom the endoscopic findings improved after h. pylori eradication and the russell bodies disappeared .\nthe present patient was negative for h. pylori and had not undergone h. pylori eradication .\nhis treatment consisted of administration of a ppi and gastrojejunostomy , which are assumed to have contributed to the resolution of the local inflammation . as for the correlation with the degrees of inflammation at the ulcer site\n, the russell bodies would be expected to appear and disappear as the degree of inflammation changed .\nthe prognosis was favorable with the internal use of a ppi in cases of rbg negative for h. pylori .\nthere have been no published reports of recurrence or malignant transformation during follow - up .\nhowever , it is often difficult to distinguish russell bodies from plasmacytoma , mucosa - associated lymphoid tissue lymphoma , and signet ring cell carcinoma .\nmultiple endoscopic observations and biopsies , like that used in the present case , are required to diagnose malignant disease .\nthis was a valuable case in which the clinical and pathological features of rbd , an extremely rare disease , could be compared in the present patient from onset to healing .", "answer": "a 64-year - old man was found to have a nodule in his right lung . \n he also complained of nausea and abdominal pain during the clinical course . \n esophagogastroduodenoscopy revealed a duodenal ulcer associated with severe stenosis and a suspicion of malignancy . \n however , three subsequent biopsies revealed no evidence of malignancy . \n the fourth biopsy showed scattered large eosinophilic cells with an eccentric nucleus , leading to a diagnosis of russell body duodenitis ( rbd ) . \n rbd is an extremely rare disease , and little is known about its etiology and clinical course . \n the pathogenesis of rbd is discussed based on our experience with this case .", "id": 79} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey give rise to all the other major brain cell types , which include oligodendrocytes , astrocytes , and neurons .\nhowever , molecular pathways , which are complicated and control the proliferation and differentiation of nscs , have been characterized incompletely to date . there is multiple indirect evidence suggesting a critical role of mirnas in nscs [ 47 ] .\npost - transcriptional control mediated by mirnas was identified as a further important regulation level , especially in neural proliferation where the action of these negative modulators of gene expression is pervasive .\nmirnas are small single - stranded non - coding rnas molecules which participate in the transcriptional regulation of eukaryotic genes and produce biological effects through inhibiting translation or destabilizing target mrnas [ 1012 ] .\nmirnas act as vital adjusters in multiple biological processes , including cell metabolism , differentiation , proliferation , and apoptosis .\nmir-126 is highly enriched in endothelial cells and previous studies found that mir-126 plays critical roles in vascular integrity and can promote angiogenesis during embryonic development [ 1518 ] .\nreported that the expression level of mir-126 was downregulated after spinal cord injury and that it can promote angiogenesis and attenuate inflammation in rats .\nhowever , the effects of mir-126 in nscs is still unclear ; therefore , we intended to study its role in nscs proliferation and survival .\nthe immortalized human nsc lines hb1.f3 and hb1.a4 were maintained with dulbecco s modified eagle s medium ( dmem , sigma ) containing 10% fetal bovine serum ( fbs ) .\ntotal rna was extracted from cell lines with a mirvanamirna isolation kit ( applied biosystems , foster city , ca , usa ) according to the manufacturer s instructions .\nthe expression level of mir-126 was detected by qrt - pcr according to the taqman mirna assays protocol ( applied biosystems ) and normalized by u6 small nuclear rna ( rnu6b ; applied biosystems ) with the 2 method .\nlv3-pglv - h1-gfp+puro plasmids with mir-126 mimics and negative control ( lv - mir-126 and lv - mir - nc ) were purchased from genepharma ( shanghai , china ) . hb1.f3 and\nhb1.a4 stably expressing mir-126 were established by transfecting lentivirus according to the manufacturer s instructions .\ncells were plated in 96-well plates in triplicate at approximately 1000 cells per well and cultured in the growth medium .\ncells were then treated with the indicated reagent and the numbers of cells per well were measured by the absorbance ( 450 nm ) of reduced water - soluble tetrazolium salt ( wst ) at the indicated time points .\ncells were plated into 6-well plates at a density of 1000 cells / well in 2 ml medium .\nthe colonies were observed using a phase - contrast microscope at a magnification of 4 ( we counted the colonies containing at least 50 cells ) .\ncells were transfected with mir-126 mimics or their respective controls and were harvested after transfection at 48 hours and then marked with the annexinv / pi double staining kit ( bd biosciences , usa ) according to the manufacturer s instructions .\nflow cytometry was used to assess the apoptotic cells in triplicates and all assays were repeated at least 3 times .\nstudent s t test or one - way anova were used for analysis when appropriate .\nthe immortalized human nsc lines hb1.f3 and hb1.a4 were maintained with dulbecco s modified eagle s medium ( dmem , sigma ) containing 10% fetal bovine serum ( fbs ) .\ntotal rna was extracted from cell lines with a mirvanamirna isolation kit ( applied biosystems , foster city , ca , usa ) according to the manufacturer s instructions .\nthe expression level of mir-126 was detected by qrt - pcr according to the taqman mirna assays protocol ( applied biosystems ) and normalized by u6 small nuclear rna ( rnu6b ; applied biosystems ) with the 2 method .\nlv3-pglv - h1-gfp+puro plasmids with mir-126 mimics and negative control ( lv - mir-126 and lv - mir - nc ) were purchased from genepharma ( shanghai , china ) . hb1.f3 and\nhb1.a4 stably expressing mir-126 were established by transfecting lentivirus according to the manufacturer s instructions .\ncells were plated in 96-well plates in triplicate at approximately 1000 cells per well and cultured in the growth medium .\ncells were then treated with the indicated reagent and the numbers of cells per well were measured by the absorbance ( 450 nm ) of reduced water - soluble tetrazolium salt ( wst ) at the indicated time points .\ncells were plated into 6-well plates at a density of 1000 cells / well in 2 ml medium .\nthe colonies were observed using a phase - contrast microscope at a magnification of 4 ( we counted the colonies containing at least 50 cells ) .\ncells were transfected with mir-126 mimics or their respective controls and were harvested after transfection at 48 hours and then marked with the annexinv / pi double staining kit ( bd biosciences , usa ) according to the manufacturer s instructions .\nflow cytometry was used to assess the apoptotic cells in triplicates and all assays were repeated at least 3 times .\nibm spss 19.0 statistical software was used to analyze the data . student s t test or one - way anova were used for analysis when appropriate .\nto further study the potential function of mir-126 in nscs , hb1.f3 and hb1.a4 were stably transfected with mimics or negative control ( nc ) .\nas indicated in figure 1a , mir-126 mimics showed good overexpression effects both in hb1.f3 and hb1.a4 and both cell lines overexpressing mir-126 showed marked cell growth increase ( figure 1b , 1c ) . to further confirm the function of mir-126 on cell proliferation and growth , soft agar colony formation assay was performed .\nas shown in figure 2a , 2b , the colony formation was significantly increased by mir-126 compared with the negative control group .\nwe next investigated the function of mir-126 in the regulation of cell apoptosis by flow cytometry .\ncells overexpressing mir-126 displayed a significant decrease in the apoptotic rate when compared with the control group ( figure 3a , 3b ) .\nthese results suggest that mir-126 may inhibit apoptosis in nscs , which may contribute to the growth induction features of mir-126 .\nto further study the potential function of mir-126 in nscs , hb1.f3 and hb1.a4 were stably transfected with mimics or negative control ( nc ) .\nas indicated in figure 1a , mir-126 mimics showed good overexpression effects both in hb1.f3 and hb1.a4 and both cell lines overexpressing mir-126 showed marked cell growth increase ( figure 1b , 1c ) . to further confirm the function of mir-126 on cell proliferation and growth , soft agar colony formation assay was performed .\nas shown in figure 2a , 2b , the colony formation was significantly increased by mir-126 compared with the negative control group .\nwe next investigated the function of mir-126 in the regulation of cell apoptosis by flow cytometry .\ncells overexpressing mir-126 displayed a significant decrease in the apoptotic rate when compared with the control group ( figure 3a , 3b ) .\nthese results suggest that mir-126 may inhibit apoptosis in nscs , which may contribute to the growth induction features of mir-126 .\nthey can profoundly regulate the expression of massive target genes that encode proteins , which may finally lead to the change of biological function .\nmir-126 , which is located in intron 7 of the egf - like domain 7 ( egfl7 ) gene , is a microrna that is highly enriched in endothelial cells and regulated by the transcription factors ets-1 and ets-2 in endothelial cells .\nprevious studies found that mir-126 promoted angiogenesis during embryonic development and after injury by targeting spred1 and pik3r2 .\nalso , knockdown of mir-126 resulted in delayed angiogenic sprouting , collapsed blood vessels , widespread hemorrhages , and partial embryonic lethality during zebrafish and mouse embryogenesis .\nit is also involved in cell growth regulation in several organs , such as colorectal cancer , gastric cancer , and liver carcinoma , by regulating multiple target genes , including insulin receptor substrate , p85 , pi3k , akt , and crk [ 2629 ] .\nreported that mir-126 plays an important role in angiogenesis and inflammation after contusion spinal cord injury in rats .\nin the current study , we verified that when the expression level of mir-126 was overexpressed by mimics transfection , the proliferation and survival of nscs were both significantly promoted .\ncck8 assay and colony formation assay both demonstrated that mir-126 can induce the proliferation of nscs .\nalthough the mechanism is not yet completely understood , our study provides further evidence in this area .", "answer": "backgroundthe aim of this study was to investigate the potential function of mir-126 in neural stem cells ( nscs).material / methodsexpression level of mir-126 was detected by quantitative real - time pcr ( qrt - pcr ) . \n mir-126 overexpression was established by transfecting mir-126 mimics into human nsc lines ( hb1.f3 and hb1.a4 cells ) . \n its effects on cell proliferation were studied using cell - counting kit-8 ( cck8 ) assay , colony formation assays . \n flow cytometry was performed to evaluate the effect of mir-126 on cell survival.resultscck8 assay and colony formation assay showed that overexpression of mir-126 promoted cell proliferation and increased colony numbers in hb1.f3 and hb1.a4 cells . \n the flow cytometry confirmed the results that mir-126 inhibited cell apoptosis.conclusionsmir-126 promoted the proliferation and survival of nscs .", "id": 80} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe dietary magnesium intake tends to be lower than that recommended worldwide even in western countries .\nseveral factors have been identified to be trigger for lowering magnesium intake including the waterborne magnesium factor , the loss of magnesium during food refining , and the magnesium content of vegetarian diets , as well as various metabolic situations such as hypertension , pregnancy , osteoporosis , drug therapy , alcoholism , stress , and even cardiac trauma .\nmagnesium is the most abundant intracellular divalent cation that is important for physiological processes including neuromuscular function and maintenance of cardiovascular tone . \nthe importance of magnesium intake in relation to cardiovascular diseases has been increasingly described , so that its intake can be inversely related to the risk of hypertension and type 2 diabetes mellitus and may improve serum lipid profiles .\nrecent surveys in sweden [ 3 , 4 ] have indicated that vegetarian diets provide a more adequate intake of magnesium , as illustrated in table 4 . note that the magnesium intake of men and women on vegetarian diets was considerably greater than the rda requirement ; this was attributed to the high intake of vegetables and whole - grain cereals by these individuals .\nrecent studies have shown that some components of the mediterranean diet such as vegetables , legumes , and nuts are rich sources of magnesium ; therefore , it seems that the high adherence to the mediterranean diet is associated with high consumption of magnesium .\nalthough the main dietary regimen of iranian population is mediterranean diet components especially the major sources of magnesium , the rate of coronary artery disease ( cad ) risk factors among this population has been considerably high . therefore , in the present study , we tried to determine effect of mediterranean dietary approach on laboratory parameters related to cad risk factors with the focus on serum magnesium concentration among iranian patients with cad .\nbaseline characteristics and clinical data of 102 consecutive patients with the diagnosis of cad and candidates for isolated coronary artery bypass surgery were entered into the study .\nstudied data were collected by the review of clinical recorded files in the day of admission . in this study ,\ncad was considered significant if there was a 75% or greater stenosis in the cross - sectional diameter and 50% or greater stenosis in the luminal view . \nblood samples were drawn from the corresponding peripheral vein into vacutainer tubes after 1214 h of overnight fasting and before operation .\nplasma glucose concentrations were assessed by means of a glucose hexokinase method ( pars azmoon kits accredited by bioactiva diagnostica , germany ) . serum total cholesterol , hdl cholesterol , and triglycerides were measured via enzymatic techniques ( pars azmoon kits accredited by bioactivadiagnostica , germany ) .\nthe friedewald formula was used to calculate low density lipoprotein ( ldl ) cholesterol , except when the triglyceride level was >\nblood pressure was calculated as the mean of two measurements , performed in the sitting position after 5 minutes of rest , using a random - zero sphygmomanometer ( hawksley - gelman , lancing , sussex , uk ) .\nc - reactive protein ( crp ) level was measured by immunoturbidimetry ( pars azmun , iran ) , and lipoprotein(a ) was measured using tint eliza ( biopool , usa ) .\ncreatinine was measured with jaffe reaction ( parsazmon kit , tehran , iran ) using an autoanalyzer ( hitachi , tokyo , japan ) .\nstudied patients were also interviewed on admission to surgical ward and before operation to report the consumption of food items listed as the number of times per day , per month , or per year during the previous year .\nwe assessed nutritional status by a validated food frequency questionnaire ( ffq ) , previously validated in iran and a 24-hour dietary recall questionnaire to record the types , amounts , and frequencies of foods consumed .\nsum of the consumption of each of several food items was used to determine the overall consumption of the food group to which each item belonged [ 9 , 10 ] .\nthe diet score was calculated on the basis of mediterranean diet quality index ( med - dqi ) that the construction of the score for this index ( table 1 ) .\nthe index assigns a score of 0 , 1 , or 2 according to the daily intake of each of the seven components and then final score was reported as a summation of all nutrient scores ranged between 0 and 14 .\nwe divided studied patients into two groups according to the final score : the groups with final score lower than 5 ( n = 35 ) and those who had final score between 5 and 10 ( n = 67 ) .\nwe compared categorized variables between the two above groups using chi - square test or fisher 's exact test if required .\nmultivariate linear regression analysis was used to investigate the potential confounding effects of patients ' characteristics and clinical data on the association between serum magnesium concentration and mediterranean regimen score .\nall the statistical analyses were performed using spss version 13.0 ( spss inc . , chicago , il , usa ) .\nstudied patients had the mean age of 58.8 year ( ranged between 38 and 78 years ) and 40.2% of them were male .\nhyperlipidemia and hypertension were observed in 75.5% and 56.9% of patients , respectively , and 51.0% of them were diabetics .\nhalf of the studied patients had moderate functional class , but three coronary arteries were involved in the majority of them ( table 2 ) .\ncomparison of the concentrations of serum laboratory parameters between the two groups with lower mediterranean dietary score and group with higher dietary score showed no significant differences between the concentration of albumin , last fasting blood sugar , last creatinine , and lipid profiles ( table 3 ) ; however , serum magnesium concentration in the group with dietary score between 5 and 10 was lower than that in group with higher score ( p = 0.026 ) .\nlinear multivariate regression analysis also showed that the lower mediterranean dietary score was a predictor for serum magnesium concentration after adjusting for confounders ( table 4 ) .\nrecent studies could confirm the cardioprotective role of intravenous magnesium for prevention of cardiac arrhythmia , pump dysfunction , and death in patients with cad , especially in the immediate postinfarction period [ 12 , 13 ] .\nmagnesium can inhibit the influx of calcium in vascular smooth muscle cells and therefore inhibit arrhythmic recurrence and the production of il-6 and mmp-1 after reperfusion and prevent the increase of myocardial lesions caused by calcium overload on myocytes .\nhowever , effect of dietary intake of this mineral on control and inhibition of cad risk factors has been questioned .\nsome researchers have been hypnotized that the low intake of magnesium may be related to the least degree of cardiovascular disease [ 15 , 16 ] .\nsome others could show that the dietary magnesium intake can be inversely associated with fasting serum insulin , plasma high density lipoprotein - cholesterol , and systolic and diastolic blood pressure . in the present study\n, we showed the potential effect of mediterranean dietary regimen on increasing of serum magnesium concentration that can mainly lead to the favorite control and prevention of cad risk factors .\nwe have shown that not only intravenous magnesium administration can be related to the lower risk of poor outcome in patients with cad , but also these effects can be obtained by dietary intake of this mineral via mediterranean dietary regimen . in a similar study by schrder\n, it was found that the high consumption of vegetables , fruits , legumes , nuts , fish , cereals , and olive oil as main components of mediterranean regimen led to high absorption of magnesiumin obesity and type 2 diabetes . also , singh showed that the increased intake of dietary magnesium in association with the general effects of a nutritious diet can offer protection against cardiovascular deaths among high - risk individuals predisposed to cad .\nfurthermore , in another study , it was observed that the intake of dietary magnesium was associated with a reduced risk of cad ; however , associations between dietary magnesium and coronary events occurring after fifteen years of follow - up were modest .\nit seems that the mediterranean dietary regimen and its components as rich pools of magnesiummight optimize micronutrient status in main body organs especially cardiovascular system . in the present study\n, it was also found that the patients ' baseline characteristics and even severity of cad had no relationship with serum magnesium concentration in multivariate analysis .\nsimilarly , in a study by mataix et al . , the risk of hypomagnesemia was not associated with any of the other factors that were investigated such as gender , educational level , obesity , smoking habits , alcohol consumption , and physical exercise .\nhowever , some studies showed that the magnesium intake could decrease in advanced age and in men for each of the different race or ethnic groups .\nit seems that the serum magnesium changes are mainly dependant on nutritional habit , metabolicprocesses , inflammatory biomarkers , and other related - potential mechanisms that should be investigated in future studies . in conclusion , taking mediterranean dietary regimen can be associated with increased level of serum magnesium concentration , and thus this regimen can be cardioprotective because of its effects on serum magnesium .", "answer": "background . \n recent studies confirmed cardioprotective role of intravenous magnesium for the prevention of cardiac events , but effect of dietary intake of this mineral via recommended dietary regimens on control and inhibition of coronary artery disease ( cad ) risk factors has been questioned . \n the aim of the present study was to determine effect of mediterranean dietary approach on serum magnesium concentration among iranian patients with cad . \n method . \n baseline characteristics and clinical data of 102 consecutive patients with the diagnosis of cad and candidates for isolated coronary artery bypass surgery were entered into the study . \n laboratory parameters especially serum magnesium concentration were measured after 1214 h of overnight fasting and before operation . \n nutritional status was assessed by food frequency questionnaire and the diet score was calculated on the basis of mediterranean diet quality index ( med - dqi ) . \n results . \n no significant differences were found in the concentrations of albumin , last fasting blood sugar , last creatinine , and lipid profiles between the groups with mediterranean dietary score < 5 and the group with higher dietary score ; however , serum magnesium concentration in the first group was higher than that in the group with higher dietary score . \n linear multivariate regression analysis showed that the lower mediterranean dietary score was a predictor for serum magnesium concentration after adjusting for confounders . \n conclusion . \n taking mediterranean dietary regimen can be associated with increased level of serum magnesium concentration , and thus this regimen can be cardioprotective because of its effects on serum magnesium .", "id": 81} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nauricular defects characterized by absence of the pinna may be congenital ( microtia or anotia ) or acquired as a result of infection , cancer surgery , or traumatic injury .\ncongenital defects may be associated with auditory canal , middle ear , and inner ear malformations .\nthe total or partial pinna mutilation may be a consequence of a car accident , war collateral damage , or chemical burn .\nrecently an increase in the number of patients presenting with pinna lesions due to chemical assault burns , occurring in the domestic or industrial setting , has been reported . whatever the cause , absence of the pinna is an important aesthetic problem , with a permanent effect on the patient 's quality of life , which can often cause severe psychological distress .\nthe modern era of pinna reconstruction surgery has its foundations in the techniques proposed by tanzer , brent , and nagata [ 46 ] .\nthe differing techniques for reconstructive plastic surgery of the auricular defect involve usually the insertion of autogenous rib cartilage framework under the skin .\nother surgeons have suggested the employment of prostheses made of synthetic material as a good alternative to autogenous costal cartilage [ 7 , 8 ] .\nthe reconstructive plastic surgery techniques based on the use of autologous cartilage inserts normally require repeated surgery acts at both implant site and donor site .\nthis creates a significant discomfort both for the pain complained about by the patient and for repeated hospital admissions to the detriment of quality of patient life .\ninitially , these epitheses were held in place by adhesives that , however , provided poor results in terms of stability and were often associated with skin irritations and deterioration of the prosthesis caused by the adhesive substances . also these defects imply a deterioration of patient quality of life .\ncurrently a superior , innovative surgical technique exists that allows fixation of the ear epitheses by osseointegrated titanium implants ( cochlear bone anchored solutions ab , sweden ) .\nbasically , this approach reflects an evolution of the implants developed for dental prostheses as proposed by brnemark in 1969 , which have been used for over 40 years in the field of odontostomatology and subsequently were proposed for application with osseointegrated craniofacial implants for use with bone - conduction hearing implant solutions [ 9 , 10 ] . in our study , we describe our experience using these pinna prostheses in 27 patients treated in the last three years .\nwe discuss the indications for auricular epithesis implant , the surgical technique , and outcomes .\nour case series comprised 27 patients ( 24 males and 3 females with a mean age of 33.1 years , range 1687 years ) ( table 1 ) .\nthe etiology was congenital in 17 patients ( figure 1 ) who were affected by microtia , while eight had posttraumatic mutilation ( figure 2 ) and two surgical amputation due to neoplasia ( figure 3 ) .\nsix of the patients with microtia and three of the patients affected by traumatic mutilation had previously undergone plastic reconstructive surgery with rib cartilage grafting and were not satisfied with the results .\nthese patients requested to have their previously reconstructed ear removed and replaced with an epithesis .\none patient ( patient 12 ) had previously undergone surgery , in a different hospital , using bone - anchored titanium implants but one of the abutments had broken because of a further unlucky trauma .\nafter six weeks , all the implants were osseointegrated and a retentive bar was fixed to the abutments .\nthe patients with microtia were offered the option of undergoing treatment with a bone - conduction hearing implant solution ( e.g. , baha ) to concomitantly address their hearing needs in parallel to the auricular rehabilitation with the bone - anchored epitheses .\nall patients declined the hearing treatment option , preferring to have the option at a later stage instead . before the surgical field is prepared and with the patient 's face still fully and easily visible , the implant sites should be carefully marked , using methylene blue , down to the bone .\nthese are ideally placed approximately 20 mm from the center of the external auditory canal opening or anticipated opening .\nthey are positioned at 8 o'clock and 10:30 on the right side and at 4 o'clock and 1:30 on the left side . in the presence of a complete malformation ,\nthe supposed location of the external auditory canal is determined by considering a triangle traced on the contralateral hemiface using the following references : the line between the lateral canthus and the auditory canal , the line between the auditory canal and the labial commissure , and the angle formed by these two lines ( figure 1(b ) ) .\nwe usually perform one - stage surgery , removing tags and remnants in cases of microtia and performing the necessary subcutaneous tissue reduction .\nthe one - stage surgical procedure can be used in adults to treat auricular defects involving nonirradiated tissue ; the two - stage technique should usually be chosen for paediatric patients and for the treatment of orbital and midface defects and auricular defects in patients with poor bone quality .\ndrilling begins using the guide drill with the spacer kept on 3 mm . during drilling\nthe bottom of the hole is repeatedly checked for bone at the base of the site .\nif there is adequate bone thickness , drilling continues to a depth of 4 mm .\nthe next step is to widen the hole to the exact diameter using a 3 or 4 mm drill countersink .\nthe low - speed setting should be used for implant insertion . in compact cortical bone , a torque setting of 40 ncm is recommended , whereas , in soft bone , a lower torque setting of 20 ncm should be used . the self - tapping fixture with the premounted fixture mount\nit is then picked up with the connection to the hand piece , which is placed into the drill hand piece .\nthe implant is installed without cooling irrigation until the small grooves at the distal end of the implant are well within the canal .\nwhen the flange of the implant has seated , the hand piece will automatically stop .\nthe titanium standard abutment is picked up with the abutment holder and placed into the implant .\nfinally a gauze dressing is applied in a figure eight form ( i.e. , foam dressing , soft silicone wound contact layer , or antiseptic dressing ) around the abutments .\nall patients were discharged the day after surgery and were revised for the first dressing after seven days .\nthe implants occurs six weeks after implant to permit sufficient healing and stabilization of the implants . following healing and stabilization of the surgical site\n, the patient was sent to the anaplastology technician who prepared the epithesis , modeling it with reference to the contralateral ear and carefully matching the individual 's skin colour ( figures 3(b ) and 3(d ) ) .\nthe definitive one has two sides : the inner one is an acrylic plate with clips that allow the attachment to a gold - platinum bar fixed to the abutments and the external one is made of soft silicone .\nthe patients receive two epitheses of different colours : a pale one for winter and a tanned one for summer . when the process of osseointegration is complete , the prosthesis , which has clips , can be easily and securely attached to , or removed from , the gold - platinum cylinder - and - bar system ( figures 3(c ) and 3(d ) ) .\nnone of the patients we treated experienced problems related to the implants over six months to three years ( osseointegration failure or wound healing problems ) .\nonly one patient encountered a relatively exuberant scar in the area of surgical remnants removing .\nthe patients were evaluated for their quality of life , during the week before pinna reconstruction with the short form health survey ( sf-12 ) as a baseline assessment ( t0 ) .\nstatistical analysis of changes over time was performed via pearson correlations , with a significant change deemed by p 0.05 .\nstatistical analysis adopting sf-12 score ( short - form health survey , 12 items ) suggests a significant role in quality of life of patients who underwent auricular rehabilitation .\nall our patients expressed their satisfaction regarding the short hospitalization and reduced invasiveness compared to other alternative therapies .\nthey had no adverse psychological reactions ; instead , they were able to resume social relations and usual physical activities .\nabsence of the ear , congenital or resulting from trauma or surgery , is a defect that can be resolved through reconstructive plastic surgery .\nthe surgical reconstruction of pinna defects remains a challenging task typically requiring multiple operations with often compromised aesthetic results .\nthis involves the insertion of either an autogenous rib cartilage framework or a prosthesis made from synthetic material into a subcutaneous pocket behind the ear , created through tissue expansion . in the past , if surgical reconstruction was refused , a patient could undergo an alternative rehabilitative approach using an adhesive - retained prosthesis .\nthe reconstruction using rib cartilage has some inherent disadvantages : it requires more than one surgical procedure , the risk of complications is relatively higher both at the implant site ( e.g. , infections , bleeding , haematoma , necrosis , and skin graft or cartilage graft exposure ) and at the donor site ( e.g. , infections , haematoma , and scarring ) .\npatients are very often dissatisfied with the final outcome because their new ear looks considerably different from the contralateral one and does not meet their expectations [ 13 , 14 ] .\nwellisz proposed the use of medpore prostheses made from porous polymer material inserted in subcutaneous pockets .\nthis procedure is frequently complicated by partial or total rejection and further build - up of scar tissue .\nthe use of adhesive - retained prostheses is also not without its issues , that is , dermatitis resulting from contact with the adhesives , unpredictable reliability of retention , variability of positioning of the prosthesis , and poorer hygiene directly attributable to the tackiness of the adhesive , as well as a decreased life span of the prosthesis resulting in an increased number of device renewals .\nrecent studies described the use of osseointegrated auricular prostheses as a good alternative treatment to surgical reconstruction . in this\nregard , titanium implant systems for bone - anchored implantable hearing solutions have shown us how such prostheses can be attached safely , securely , reproducibly , and without the need for adhesives [ 11 , 1517 ] .\nthe procedure discussed in this paper is suitable for patients who are unwilling to undergo plastic reconstructive surgery utilizing rib cartilage , which remains a challenging surgical procedure that involves more than one surgical step and is associated with the risk of complications at the donor site and/or the acceptor site .\nsimilarly , in cases of pinna amputation ensuing following damage to the pinna from chemical burns , the usual techniques of plastic surgery employed hold their inherent difficulties as they involve procedures that require the presence of large areas of intact skin around the lesion ( necessary for the preparation of sliding skin flaps or the use of tissue expanders prior to the placement of subcutaneous implants ) . subsequently ,\nthe use of these implants is also the only possible solution in cosmetic treatment of oncology patients who have previously undergone several surgical procedures and/or radiotherapy .\nradiotherapy does not constitute a contraindication for this procedure , although implant loss is relatively higher in irradiated cases than in nonirradiated cases at the site of treatment .\ngranstrom reported that the adjunctive use of hyperbaric oxygen could ultimately reduce the risk of implant loss .\nit is important to note the reasonably low cost of the implants and epithesis : typically amounting to a total of less than 4000 euros . in all previous reports patients\nexpress their satisfaction regarding the short hospitalization and reduced invasiveness compared to other alternative therapies .\n. local skin infection around the fixture could occur , as could the formation of granulation tissue and keloids .\nthese are complications that can be avoided or resolved using appropriate medication and topical treatments without loss of the fixture .\nabsolute contraindications for the use of titanium bone implants in prosthetic reconstruction of the auricle are exceptional and may be local or general conditions ( i.e. , resp . ,\ncontraindications for general anaesthesia need not preclude use of these implants since they can be positioned equally well under local anaesthesia .\nthis surgical technique is contraindicated in patients younger than 14 years of age , whose skull thickness is not sufficient to support the osseointegrated implant .\npreoperative evaluation of bone thickness via ct scans should , nevertheless , be a mandatory part of the surgical planning in all the patients [ 1517 ] . as mentioned earlier , indications for one - stage surgery are auricular defects , adult patients , and nonirradiated tissue , while two - stage technique should be used in young patients ( 1417 years old ) and to treat orbital and midface defects and auricular defects in patients with poor bone quality .\nconductive hearing loss due to malformations of the external and middle ear presents in all subjects affected by microtia and can be corrected by combining the placement of titanium implants for auricular rehabilitation with implantation of the fixture and abutment for a baha . in this way , both the sensory and the aesthetic problems can be resolved in a single operation . however , it should be pointed out that all the patients in our series refused to undergo baha implantation after testing the device prior to surgery ; these patients , being well accustomed to hearing on only one side , found the increased auditory perception provided by the baha disorienting and irritating .\nthe pinna epithesis fixed with bone - anchored titanium implants technique is characterized by excellent aesthetic outcome and lasting results .\nfor example , they are able to use also helmet required for some sport activities and can swim without the problems related to adhesive epitheses .", "answer": "different surgical solutions have been proposed for reconstruction of the auricle following loss of the pinna through traumatic injury or neoplastic disease or in patients with congenital defects . \n surgical treatment may involve the insertion of an autogenous rib cartilage framework or the use of a porous polymer material inserted into an expanded postauricular flap . \n reconstruction with rib cartilage has yielded good results but requires more than one surgical step , and adverse events can occur both at the donor and at the acceptor site ; cases of prosthesis rejection have also been described following application of the polymeric prosthesis . \n the use of a titanium , dowel - retained silicone prosthetic pinna , fixed to the temporal bone , has recently been proposed . \n this useful surgical approach is indicated particularly after resection of the pinna caused by neoplastic disease or in traumatic auricular injury . \n osseointegrated titanium implants used in 27 patients in this study provided them with a safe , reliable , adhesive - free method of anchoring the auricular prostheses . \n the prostheses allowed recovery of normal physical appearance and all the patients reported that they were completely satisfied with the outcome of the surgical reconstruction . \n no surgical complications , implant failures , or prosthetic failures were encountered over six months to three years .", "id": 82} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrhabdomyolysis is characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation .\nthe spectrum of the syndrome ranges from asymptomatic serum muscle enzymes elevation to life - threatening extreme enzyme elevations , electrolyte imbalances , and acute renal failure .\nwe report an elderly lady with a combination of risk factors who developed rhabdomyolytic acute renal failure .\na 65-year - old lady was suffering from type 2 diabetes for the past 30 years , hypertension for the past 20 years , and coronary heart disease for the past 10 years .\nthe medications included clopidogrel 75 mg / day , amlodipine 10 mg / day , frusemide 40 mg bds , and insulin .\na week before presenting to us , a cardiologist had added atorvastatin 10 mg / day to her prescription .\nshe presented to us with complaints of severe generalized myalgia , difficulty in assuming upright posture from sitting position , and difficulty in walking of 1 week duration .\nshe also complained of swelling of feet , face , nausea , loss of appetite and noticed decreased urine output , and reddish discoloration to urine for the last 3 days .\nthere was no fever , history of trauma , viral exanthem , severe exercise , seizure , uncontrolled blood glucose , and use of herbal medication preceding the illness . on examination\n, she was well - built and well - nourished , and had pedal edema and facial puffiness .\nshe was afebrile with pulse rate of 60 beats per min and blood pressure of 160/90 mm hg .\nneurological examination showed 2/5 power in all four limbs , absent deep tendon reflexes , and muscle tenderness with no sensory involvement .\nurinalysis showed glucose 2 + , ketone bodies negative , blood positive , red blood cells nil , and white blood cells 1 - 2/hpf .\nher hemoglobin was 11.4 g / dl , total leukocyte count 18 , 300 per mm , platelet count 5.0 lakh per mm , esr 20 mm after 1 h , electrocardiogram showed tall peaked and widened t waves with proximal limb steeper than distal limb , and the chest radiograph was normal .\nultrasound abdomen showed right kidney 9.3 3.7 cm and left kidney 9.2 3.2 cm .\nthe urine and blood cultures were sterile , hiv , hbsag , anti - hcv antibodies , anti - hav igm , and anti - hev igm were negative .\nmyalagia , reddish discoloration to urine , deterioration of renal function , elevated sgot , creatinine kinase , and increased urine myoglobin led to the diagnosis of rhabdomyolysis .\nlevothyroxine replacement was initiated at a dose of 50 g / day , increased after 15 days to 100 g / day .\nthe following three risk factors for the onset of rhabdomyolysis were identified : use of statin , undiagnosed hypothyroidism , and co - administration of amlodipine and clopidogrel .\nfrusemide was stopped as she had hypokalemia before the onset of illness which was again a risk factor for rhabdomyolysis .\nafter seven sessions of hemodialysis the urine output improved and serum creatinine stabilized at 3.2 mg / dl .\nhowever , it is difficult to directly compare the incidence of statin myopathy in clinical trials with real world clinical practice given the inconsistent definitions .\nthe common risk factors for the development of a statin - induced myopathy include high dosages , increasing age , female sex , renal and hepatic insufficiency , diabetes mellitus and concomitant therapy with fibrates , cyclosporine , macrolide antibiotics , warfarin , and digoxin .\nindividual statins differ in their risk of inducing rhabdomyolysis , with some patients developing this syndrome when switching from one statin to another .\nit is probable that genetic factors play a role in the pathogenesis of this syndrome .\nthe temporal relation between statin therapy and the onset or resolution of myopathy is not fully defined .\na retrospective study of 45 patients with statin myopathy at a tertiary center revealed a mean therapy duration of 6.3 months before symptom onset and a mean duration of 2.3 months for symptom resolution after discontinuation of statin therapy .\npatients in primo study developed muscle symptoms after a median of 1 month after initiation of statin therapy , ranging up to 12 months after initiation .\nhypothyroidism was reported as a predictor of statin - associated myopathy ( or 1.71 ; ci , 1.10 - 2.65 ) in primo study .\nthe likely mechanisms of renal impairment in hypothyroidism are the reduction in glomerular filtration rate due to the lower cardiac output and renal blood flow , thyroxine may mediate tubular secretion of creatinine , hypothyroidism may increase creatinine release from muscle , and rhabdomyolysis .\nit is possible for two different substrates of the same metabolizing enzyme to compete for catalytic sites on the same enzyme ; through competitive inhibition , one substrate may gain access to these sites whereas the other is excluded .\nthis process results in metabolism of the drug that successfully accesses the catalytic sites of the enzyme , whereas the excluded drug is metabolized at a significantly slower rate . in the present patient\nthe present patient provided a caution that hypothyroidism and interaction with other drugs should be considered when patients were going to be initiated on statins .", "answer": "rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation . \n we report a patient with chronic kidney disease who had deterioration of renal function due to combination of risk factors like hypothyroidism and interaction of amlodipine and clopidogrel with statins .", "id": 83} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe tree of life ( tol ) is a widely used metaphor to describe the history of life on earth . while darwin argued that the ' coral of life ' may be a more apt description ( since only the surface remains alive , supported by the dead generations beneath it ) , relationships between organisms based on shared characters are best organized using the schematic representation of a tree .\nuse of molecular markers , in particular small - subunit ribosomal rna , have allowed this metaphor to be extended to microorganisms ; however , this has also presented unique challenges for notions of phylogeny and evolution .\none of the most significant challenges is the impact of horizontal gene transfer , which causes genes that coexist in a genome to have different molecular phylogenies . despite these challenges , the increasing ease with which genomes can be sequenced has reinvigorated attempts to use genomic information to reconstruct the tol .\ntherefore , a vertical line of descent exists , and could theoretically be reconstructed as a purely bifurcating tree ( that is , an organismal or cytoplasmic tree ) .\nhowever , while evolution presupposes and requires descent via reproduction , the two are not analogous .\nevolution is , by definition , the change in the genetic material within a population of organisms across generations ; therefore , any process by which genetic material within a population changes that is unrelated to the reproduction of individuals will show a history that is unrelated to the organismal vertical line of descent .\nthe sum effect of these other genetic processes may completely obfuscate vertical descent , leaving only some measure of ' relatedness ' based on overall genetic similarity .\ntwo common approaches in constructing a genome - based tol are supermatrix analyses , in which sequence alignments for individual gene families are concatenated into a single dataset that is then used to construct a tree , and supertree analyses , in which a consensus phylogeny is constructed from multiple gene trees . in some cases ,\ndatasets are generated by finding orthologous genes in all organisms and removing all genes whose conflicting phylogenetic topologies seem to indicate horizontal gene transfer , and then using the remaining genes to reconstruct the presumed vertical lines of descent of the genomes ( see , for example , [ 4 - 6 ] ) .\nthis approach has an obvious shortcoming in that gene transfer and the resulting phylogenetic conflicts can only be inferred if each individual gene has retained sufficient phylogenetic information to enable its origin to be correctly assigned .\nfurthermore , the absence of evidence for gene transfer does not constitute evidence for the absence of gene transfer .\nthus , combining genes with different histories into a single data set will almost certainly result in a phylogeny that represents neither the history of any individual gene , nor the history of the organism as a whole .\nanother problem with supermatrix and supertree analyses is that they often give equal weight to genes that have different histories of horizontal gene transfer .\nthis results in an average or median phylogeny that may not represent organismal history ; if there are ' highways ' of gene sharing that is , large numbers of genes have , for some reason , been shared between specific groups of otherwise phylogenetically distinct organisms this can easily be mistaken for a consistent signal supporting an organismal tree . for example , because of such highways of gene sharing these types of analyses group members of the order thermotogales with the firmicutes , and the members of the aquificales with the -proteobacteria .\nin contrast , 16s rrna gene phylogenies and concatenated ribosomal protein phylogenies strongly support these two orders as deeply branching bacterial lineages ( figure 1 ) .\n( a ) extensive horizontal gene transfer at all phylogenetic levels combine to produce a ' web of life ' that often obscures the lines of descent between groups ( modified from ) .\ncopyright ( 2008 ) national academy of sciences , usa . ( b ) major microbial groups as defined by 16s ribosomal rna phylogeny .\nbands represent some avenues of extensive gene sharing involving thermotogales , aquificales , and firmicutes .\n( c ) impact on relationships between thermotogales and aquificales of genome content changes due to extensive horizontal gene transfer .\ngrey clouds represent groups of shared genes between clades that are non - monophyletic in the 16s tree .\nthe phylogeny based on these ' gene content ' clouds is quite distinct from that of 16s or other ribosome - based trees .\nif stringent criteria are applied to remove or down - weigh transferred genes from supertree or supermatrix analyses , the resulting trees at best represent the history of only a minor fraction of the genome , largely consisting of ribosomal proteins , effectively a ' tree of one percent ' . even if this remaining ' genome core ' retains a strong signal of vertical descent , this does not capture the true evolutionary history of genomes ; that is , a web where different strands depict the history of different genes .\na ribosomal tree of life has other shortcomings , in that within taxonomic orders many recombination and lineage sorting events may occur , and ribosomal genes are so highly conserved that such events at the tips of the tree may not be detectable .\nhowever , it can still provide a useful backbone for a reticulated genomic or organismal phylogeny , especially with respect to sets of genes that clearly have undergone horizontal transfer between more distantly related groups . while ribosomal protein and rna encoding genes have been transferred in the past ( see discussion in ) , these genes are resistant to transfer , with most transfers occurring between close relatives .\nthese properties make a phylogenetic reconstruction using ribosomal rna and proteins an ideal scaffold upon which to map horizontal gene transfers , clearly depicting their distinct contribution to genomic ( and organismal ) evolution .\nseveral attempts have been made to capture this web - like genome history ( see , for example , using ribosomal rrna as a backbone ( figure 1 ) .\nconceptually , this method is distinct from any ' tree of one percent ' or genome averaging approach in that rather than being discarded , genes undergoing horizontal transfer are included in the final reconstruction without obscuring the vertical signal , even if that vertical signal is preserved only in a minority of genes .\nin this issue , puigbo , wolf and koonin present an approach for salvaging the tol that is a variant on other supertree methods , in which nearly 7,000 phylogenetic trees of prokaryotic genes ( a ' forest of life ' ) are compared in order to determine a central tendency in their topologies .\nthe trees are built from clusters of orthologous groups of proteins ( cogs ) , and the central tendency is deduced from a set of nearly universal trees ( nuts ) , defined by puigbo et al . as those trees generated from a set of cogs that are represented in > 90% of the analyzed prokaryote taxa .\nwhat distinguishes their approach from earlier supertree analyses apart from the very large number of genes included in the comparison is that it does not depend on a concatenation of highly conserved proteins or rrnas , or on a supertree generated by ' pruning ' down to those genes giving a consistent topology , to determine a central tendency . instead ,\ncalculate an ' inconsistency score ' that is a measure of how representative a particular topology of each tree is to the rest of the trees in the forest of life . in reconstructing the central tendency in such a broad distribution of gene phylogenies , the work by puigbo et al . also shows the difficulty in resolving deep branches , which often simply collapse into radiations without any topological structure . in confronting this problem ,\nthey show that the relationship between phylogenetic depth and resolution supports a tree - like structure for these deep branches .\nthis result is significant in that it suggests that there is no need to postulate exotic ' big bang ' radiations early in evolution ; rather , deep phylogenies can still be represented as bifurcating evolutionary events , albeit with extremely short branches that can prove difficult ( or sometimes impossible ) to resolve . integrating the vertical descent of organisms and their genomes with the myriad phylogenetic patterns produced by horizontal gene transfer is essential for a truly comprehensive understanding of evolution .\na new method that acknowledges and promotes this integration , even if falling short of fully encompassing the intricate details of a complex genome - based biological reality , represents progress towards this goal , and it now appears that a vertical signal can be discerned , if not clearly resolved .\nwork in the authors ' lab is supported through the nsf assembling the tree of life ( deb 0830024 ) and nasa exobiology ( nag5 - 12367 and nnx07ak15 g ) programs .", "answer": "reconstructing the ' tree of life ' is complicated by extensive horizontal gene transfer between diverse groups of organisms . \n while numerous conceptual and technical obstacles remain , a report in this issue of journal of biology from koonin and colleagues on the largest - scale prokaryotic genomic reconstruction yet attempted shows that such a tree is discernible , although its branches can not be traced .", "id": 84} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na coracoid fracture is a rare orthopaedic condition as it accounts for only 2 10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures\nwe present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle .\nthe patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months\nfollow up the patient was pain free with full range of motion at right shoulder .\nconcomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs .\nct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle .\ncoracoid fractures alone are themselves a rare occurrence amounting to approximately < 0.1% of all fractures and even only 5% of all fractures of the shoulder [ 1 - 3 ] .\nno reliable figures currently exist to determine the prevalence of a simultaneous distal clavicle and coracoid fracture .\na 60 year old gardener presented with a history of injury to her shoulder as her arm was pulled by a lawn mower .\nthe patient did not have any previous injury or degenerative condition to this shoulder prior to this accident .\nphysical examination showed swelling and bruising around shoulder , tenderness and restricted movements of the right shoulder .\nct and plain radiographs of the shoulder displayed a displaced coracoid fracture and non - displaced fracture of the distal end of clavicle at the time of injury ( fig .\nthe patient was placed in a shoulder arm sling for six weeks and was then referred to physiotherapy .\nsome doubtful angulation of the coracoid process is visible but fracture is not appreciated clearly .\n1b- ct scan conforms the fracture of lateral end of clavicle and also displace coracoid fracture . at three months\nthe patient was pain free and back to working as a gardener with a free range of movement in the right shoulder .\n3 months follow up radiographs showing no further displacement of the fracture with early consolidation at the fracture site .\nwhen fractures of coracoid and distal clavicle co - exist , misdiagnosis is common because both the fractures may not be seen on standard projections .\nthe stryker notch view is recommended for detection of these fractures . furthermore ct imaging is advised if radiographs initially fail to show any bony injuries of the shoulder , but clinical examination suggests otherwise .\nthe mechanism of injury is probably the result of a resisted flexion of the arm and elbow which led to a forceful pull of the muscles , pectoralis minor and the coracobrachialis , that insert into the coracoid .\nthis has previously been described in two other case studies concomitant coracoid fractures and acromioclavicular dislocation .\nthe patient suffered an ipsilateral avulsion of the coracoid which would be considered as a type ii according to ogawa et al and a distal clavicle fracture which would be considered as a type i according to the neer s classification .\nit is to this day still controversial how to treat coracoid or distal clavicle fractures individually , let alone if they are present concomitantly .\ndetails and consequent treatment methods of coracoid fractures have also yet to be established in literature .\nogawa et al have recommended surgical treatment of coracoid fractures combined with other shoulder injuries , but have otherwise shown similar outcomes between operative and non - operative treatment of coracoid fractures alone .\nthey did however recommend non - operative management of type ii fractures as these do not disturb the scapuloclavicular connection .\nthere does not seem to be a general consensus on the treatment of distal clavicle fractures too .\nrobinson et al have recommended non - operative management of distal clavicle fractures in the middle aged or elderly patients . out of the 101 patients treated non - operatively with distal clavicle fractures , only in 14% of cases\nrokito et al compared nonoperative and operative treatment of a total of 30 type ii distal clavicle fractures retrospectively and did not reveal any significant difference in terms of ucla , constant and asesscore . on\nthe other hand haidar et al and meda etal advocate the use of clavicular hook plates .\nthese studies however did not compare the operative treatment to non- operatively treated control groups [ 10 , 11 ] .\nthe option of treating a symptomatic nonunion of the distal clavicle was described by kang et al who achieved 100% bone union in 10 patients following orif with an oblique locking t - plate and autogenous bonegraft .\nlasda et al described successful treatment of a concomitant acromioclavicular dislocation and coracoid fracture conservatively .\neleven years later carr et al further described two cases of concomitant coracoid fracture and acromioclavicular dislocation which were treated conservatively with good results .\nrecently duan et al published a case report of operative treatment of an acromioclavicular dislocation in combination with a coracoid fracture which was treated with a hook plate .\nthey described the problem of only partial bone union after 5 months and the additional plate removal that needed to be done 12 months after the initial operation .\nonly one case report by ruchelsman however has described the operative treatment of a concomitant lateral clavicle and coracoid fracture . in his case\nhe then proceeded with a open distal clavicle excision and reduction of the coracoclavicular interval with screw fixation achieving an excellent clinical outcome .\nthey commented that high index of suspicion is needed to avoid missing such combination injuries at shoulder girdle and additional radiological investigations should be done if pain at shoulder girdle is persistent .\nin view of the sparse and controversial literature available , we believe that the patient should be appropriately informed of both operative and nonoperative options treatment options . in our case the patient preferred nonoperative management which resulted in an excellent clinical result .\nconcomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs .\nct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . even in cases with displacement\na conservative management will result in a good clinical outcome as seen in our case .", "answer": "introduction : a coracoid fracture is a rare orthopaedic condition as it accounts for only 2 10 % of all scapular fractures and < 0.1% of all fractures . in even rarer cases coracoid fractures are also associated with other bony injuries of the shoulder . \n there is currently no consensus on the treatment of such injuries.case report : we present an unusually rare case of a simultaneous fracture of the coracoid process and the lateral end of clavicle . \n the patient was treated with shoulder arm sling for 6 weeks followed by physiotherapy . at 6 months \n follow up the patient was pain free with full range of motion at right shoulder.conclusion:concomitant fractures of lateral end clavicle and coracoid process are rare and may not be visible of plain radiographs . \n ct scan may be indicated if the clinical examination suspects additional injuries of shoulder girdle . \n we have treated this injury non operatively with a good clinical outcome .", "id": 85} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 23-year - old female presented with an asymptomatic , erythematous , atrophic macule on the upper right side of her back that increased gradually in size within the last four years without any symptoms ( figure 1a ) . on physical examination the surface of the lesion was smooth and no induration was examined on palpation .\ndermatoscopic evaluation of the lesion using 3gen dermlite - ii pro hr and documented with dermlite - foto 3gen ( llc , dana point , ca , usa ) showed a homogenous pigment network on a purplish erythematous background ( figure 1b ) .\nhistopathological examination of h&e ( hematoxylin and eosin ) stained sections revealed epidermal atrophy , increase in melanin in basal keratinocytes and heavy dermal cellular infiltrate composed of spindle - shaped cells arranged in a storiform pattern that extended into the subcutaneous tissue ( figure 2 ) .\nimmunhistochemical staining for cd34 was positive , while factor xiiia was negative ( figure 3a , b ) .\ndfsp is a rare , slow growing , locally invasive cutaneous neoplasm of fibrohistiocytic origin with intermediate grade malignancy with an incidence between 0.85.0 cases per 1 million persons per year .\nthe atrophic presentation of dfsp is the rarest variant of this infrequent neoplasm , which was first described in 1985 .\nthe non - protuberant dfsp can be considered the early clinical stage of dfsp before developing the typical protuberant feature unless it remains as a non - protuberant tumor that is called atrophic dfsp .\nit occurs as an atrophic , asymptomatic plaque that can be difficult to distinguish from morphea , morphea like basal cell carcinoma , scar , lipoatrophy and atrophic dermatofibroma .\nalthough the clinical appearance of atrophic dfsp is different from common protuberant type , histopathological features are similar .\natrophic presentation of the lesions may be due to the marked cellularity of the tumor cells in the dermis and infiltration to the subcutaneous fat .\nimmunhistochemical staining is important to distinguish dfsp from atrophic dermatofibroma and medallion - like dermal dendrocyte hamartoma .\nwhile dfsp cells are positive for cd34 and negative for factor xiiia , atrophic dermatofibroma cells are usually negative for cd34 and both of cd34 and factor xiiia are positive in the medallion - like dermal dendrocyte hamartoma [ 3 , 4 ] .\ndermatoscopic studies of dfsp are very rare in the literature . in 2013 , bernard et al reported the first study of dermatoscopic analysis of dfsp in 15 cases .\ndelicate pigment network , vessels , structureless light brown areas , shiny white streaks , pink background coloration and structureless hypopigmented or depigmented areas were defined as six main dermatoscopic features of dfsp . in 2014 , dermatoscopic features such as peripheral dilated vessels forming a mesh - like pattern , milky - red areas , whitish linear structures and fine pigment network were reported in a series of four cases of dfsp . to our knowledge , only one case of atrophic dfsp was presented with dermatoscopic features in the literature .\nthe reported dermatoscopic findings of that case were branching vessels on a yellowish background without pigment network .\nthe authors suggested that the dermatoscopic features might be the result of dermal atrophy and close approximation the subcutis to the epidermis .\nin contrast , our case showed dermatoscopically regular brown lines reticular on a purplish erythematous background .\nhomogenous brown lines reticular seen in our case correspond to the accumulation of melanin in basal keratinocytes , while the erythematous background is the result of dilated vessels in the dermal plexus . here , the smooth surface reflects the stratum corneum being normal .\nthe most frequent dermatoscopic pattern associated with dermatofibromas , a well - known and benign cousin of dfsp , is the central white scar - like patch and peripheral delicate pigment network .\nthe histopathologic correlation of white scar - like patch in dermatofibroma is pronounced fibrosis within the papillary dermis .\ncontrary to dermatofibromas , fibroplasia in the upper half of the dermis is uncommonly observed in dfsp which may explain the absence of white scar - like areas in our case . in conclusion , we have presented the dermatoscopic findings in an unusual case of atrophic dfsp .\natrophic dfsp should be kept in the differential diagnosis for atrophic and depressed skin lesions , particularly those seen on the trunks of women .\ndermatoscopy , a noninvasive method , may not only help to differentiate atrophic dfsp from other skin diseases but may also indicate the need for histopathological examination since the disease has prognostic significance .", "answer": "dermatofibrosarcoma protuberans ( dfsp ) is an uncommon locally aggressive mesenchymal tumor with a high local recurrence rate . \n atrophic dfsp is a rare variant of dfsp characterized by a non - protuberant lesion . \n we report on a 23-year - old female , who presented with an atrophic , asymptomatic macule on the right side of her back 2 cm in diameter . \n dermatoscopic examination revealed homogenous pigment network on a purplish erythematous background . \n the histopathological finding of the incisional biopsy material was consistent with dfsp . \n to our knowledge , this is the second case of atrophic dfsp discussing the dermatoscopic features of this relatively rare condition .", "id": 86} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmicrosatellites are simple sequence repeats ( ssrs ) that exhibit complex patterns in their frequency of occurrence , genomic distribution , mutability , function and evolution . apart from being the source of informative genetic markers , microsatellites per se\nhave attracted a lot of attention with respect to their origin , distribution , expansion , mutation and disintegration ( 17 ) .\nquestions are also asked about the functional role of microsatellites in particular and biological significance of the microsatellites in general ( 4,812 ) .\ngenetic studies and whole genome sequence analysis have established non - random distribution , variability and high mutability as characteristics of microsatellites .\nevidences are accruing , which support the role of microsatellites in gene regulation , transcription and protein function ( 13 ) .\nexistence of qualitative and quantitative differences between microsatellites of different genomes and their role in adaptive evolution have also been theorized ( 2,8 ) .\nhowever , such studies require information on type ( mono to hexa ) , motif ( gc% ) , abundance ( motif preferences ) , frequency , distribution ( linkage group - wise and chromosomal position ) , location ( exon , intron , regulatory element and transposon ) , nature ( perfect , imperfect and compound ) and copy number ( existence of paralogs ) of microsatellites not only on a whole genome basis but also as a comparative analysis of multiple genomes that are related by phylogeny ( for instance , fully sequenced primate genomes or fungal genomes or insect genomes ) to draw functional conclusions .\nwhole genome sequences of insects have lived up to the reputation of diversity and have thrown immense variability in size and organization of their genomes . among others , there are five fully sequenced insect genomes : drosophila melanogaster ( as a model organism it provides maximum annotated data ) , anopheles gambiae ( another dipteran but economically highly important as malarial vector ) , tribolium castaneum ( relatively early insect order of coleoptera ) , apis mellifera ( hymenoptera , relatively a recent insect order ) and bombyx mori ( economically important as silk - producing member of lepidoptera , members of which are crop pests ; also significant as a model for insect development ) .\nresearchers attempting to understand the biology and evolution of microsatellites are often faced with the following questions : ( i ) do microsatellites occur everywhere in the genome ? ( ii )\n( v ) does the gc content of the motif affect the length , repeat units or mutation rate of microsatellites ?\n( viii ) do microsatellites occur as families of common flanking sequences in the genomes ( paralogs ) ?\ninsatdb , unlike many other microsatellite databases that cater to only the needs of microsatellites as markers , allows users to address the above - mentioned questions by accessing qualitative and quantitative genome level microsatellites profile of a single insect or to carry out comparative genomic analysis using all the five genomes .\nt.castaneum sequences were downloaded from genbank ( ) and bombyx mori sequences were downloaded from .\nrepeats were extracted employing tandem repeat finder version 4 ( 14 ) . to ensure that the extracted repeat sequences were real microsatellites , those with less than five repeat units and shorter than 15 bp in length were excluded .\ntandem repeat finder does not employ minimal alignment score for detecting microsatellites ; rather a probabilistic model of random repeat sequences specified by per cent identity and frequency of insertions and deletions .\nthis includes calculation of average per cent identity between the copies ( pm ) and average percentage of insertions and deletions ( pi ) .\nthe algorithm has a pair of matching probability and indel probability values ( pm = 0.80 , pi = 0.10 ) as default to cover most divergent copies at every locus .\nwe used two sets of alignment parameters ( match , mismatch , gap ) , ( + 2 , 3 , 5 ) and ( + 2 , 5 , 7 ) to score the matches . all the microsatellites with a minimum alignment score of 30 are reported in the database , which means that both perfect and imperfect microsatellites are listed .\nsmit , r. hubley and p. green , unpublished data ; ) to obtain indices marking the occurrence of simple repeats , tandem repeats , segmental duplications , interspersed repeats including sines , dna transposons , retrotransposons , lines , etc .\nfurther , sequences were analysed for the delineation of exons and introns using genscan ( 15 ) . flanking sequences of microsatellites\nwere aligned to catalogue paralogous microsatellites that exhibit identical origin and hence considered belonging to the same microsatellite family .\noccurrence of two or more microsatellites contiguously with intervening non - repeat sequence of 70 bp were separately categorized as compound repeats .\nit stores microsatellites from all the five insect genomes separately as well as carries complete annotations of these microsatellites .\nthe database also provides basic information on each of the five insects and important links to obtain further knowledge , and contains a tutorial page and a glossary page .\nend users with adequate computational capabilities can batch download full complement of microsatellites ( insect - wise ) , microsatellite sequences , compound microsatellites and full list of microsatellite loci existing as families .\nthese data are made available as csv files , which are compatible with spreadsheet programmes such as ms excel .\nalternatively , details of the microsatellites with highly specific characteristics may be queried using a multi - option query sheet ( figure 2 ) .\nthe options include insect ( one at a time ) ; location ( intron , exon , i.e. boundary , upstream , intergenic , repeat elements single or in combination ) ; repeat type ( motif size , mono- to hexa - nucleotide ) or actual repeat motif ( by essentially entering up to five repeat motifs ) ; gc% ( fixed value or range ) ; repeat size in either base pairs or number of units ( fixed value or range ) ; repeat kind ( perfect or imperfect ) . once insect and location options\nthe output is primarily a list of microsatellites annotated for all options of the query sheet and the output table is generated as a hierarchical pre - sorted list .\neach microsatellite is given a unique i d that also carries genomic sequence i d and corresponding indices .\nif the number of microsatellites selected based on the options of the query sheet exceeds 500 , the output is split into sets of 500 microsatellites . in addition , a csv file containing total output is also made available for downloading . if the query options do not select any microsatellite , a message indicating zero output is displayed and a back button is provided to refine the options .\nssr motif and 100 bp each of the left and right flanking sequences are given for each microsatellite entry , which allows users to carry out sequence analysis of microsatellite vis - - vis locus .\nin addition , users can select individual microsatellites to convert them into locus - specific markers .\nthis is facilitated by automatic uploading of repeat and flanking sequences of the selected microsatellite into primer3 query form ( 16 ) .\nscreen shots of ( a ) insatdb homepage , ( b ) multi - option query sheet , ( c ) output table and ( d ) analysis page .\nour analysis showed that microsatellite content of five fully sequenced insect genomes is independent of both genome size and gc content ( table 1 ) .\nthe database consists of a dedicated section ( analysis ) that describes the types of analysis that can be carried out using the data obtained from insatdb .\nsome of the quick observations and inferences from a comparative genomic analysis are given in this section .\nmicrosatellite content of insect genomes preponderance of di- and tri - nucleotide repeats is observed in drosophila and anopheles , whereas tri- and tetra - nucleotide repeats are abundant in bombyx and tribolium . on the whole ,\nshorter microsatellites are abundant in the five insect genomes ; as the length of the microsatellite increases their number decreases logarithmically typified by bombyx and drosophila microsatellites ( > 90% of the microsatellites < 50 bp ) ; on the other hand , anopheles and tribolium have longer microsatellites in a relatively high frequency . shorter microsatellites\nnot only predominate microsatellite population in the five insect genomes , but also seem to possess higher number of imperfect repeat units . on the other hand , microsatellites spanning > 100 bp consisted of perfect , rather than imperfect repeats .\ninterruptions , if at all , occur mainly in the middle region of the repeat sequence and the ends seem to be selected against decomposition . on the whole ,\nthere is no linear correlation between gc content and the average number of repeat units .\naverage length of the microsatellite across gc range is 37 9 bp and between 0 and 5% gc content , microsatellites tend to be longer than 60 bp .\ncompound microsatellites account for nearly 3.2% in the insect genomes analysed ; owing to high density of microsatellites , apis has higher number of compound loci ( 6.12% ) .\nanopheles and apis genomes have as many as 50 and 60% of the total microsatellites in coding region , respectively .\nbombyx genome has only 10% of the microsatellites in regions spanning exons , introns and their boundary .\nmore than 70% of the microsatellites present in exons are trinucleotide repeats except in apis , where 50% tri- and 25% dinucleotide repeats are present in exonic regions .\nmicrosatellites in insects are at rich ( on an average 23.4% gc ) ; however , they exist within regions that are not always at rich .\nincorporation of microsatellite data from additional insects , query facility for better comparative genomic analysis such as gene - based microsatellite extraction and conservation analysis are planned .\nadditionally , based on users ' feedback , supplementary features will be added to make insatdb a single window system for insect genome analyses using microsatellite tools .", "answer": "insatdb presents an interactive interface to query information regarding microsatellite characteristics per se of five fully sequenced insect genomes ( fruit - fly , honeybee , malarial mosquito , red - flour beetle and silkworm ) . \n insatdb allows users to obtain microsatellites annotated with size ( in base pairs and repeat units ) ; genomic location ( exon , intron , up - stream or transposon ) ; nature ( perfect or imperfect ) ; and sequence composition ( repeat motif and gc% ) . \n one can access microsatellite cluster ( compound repeats ) information and a list of microsatellites with conserved flanking sequences ( microsatellite family or paralogs ) . \n insatdb is complete with the insects information , web links to find details , methodology and a tutorial . \n a separate analysis section illustrates the comparative genomic analysis that can be carried out using the output . \n insatdb is available at .", "id": 87} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nradial extracorporeal shock wave therapy ( rswt ) generates pressure waves through the \n collision of solid bodies1 .\nthere are a few recent \n reports regarding the effectiveness of extracorporeal shock wave therapy ( eswt ) on \n neurogenic heterotopic ossification ( ho ) in the lower extremity , but to our knowledge , the \n use of eswt or rswt to treat neurogenic ho in the upper extremity has not been reported in \n the literature4 .\nwe report 2 cases of rswt used to treat neurogenic ho in the upper extremities . in both \n cases , improvements in pain ,\nrange of motion ( rom ) , muscle strength , and hand function were \n observed .\neach patient gave their written informed consent and agreed to participate in the \n treatment .\nthis case report was approved by the ethics committee of the sahmyook medical \n center .\na 49-year - old man was admitted to our physical medicine and rehabilitation ( pmr ) \n department .\na subarachnoid hemorrhage ( sa ) occurred 10 months prior to admission and \n neurogenic ho of the left shoulder and elbow was diagnosed 2 months before his admission .\nhe \n had been taking disodium etidronate 800 mg per day ( fig . \n\n1.(a ) in case a , bone scan , x - ray , and musculoskeletal ultrasound demonstrate ho in the \n left shoulder and elbow .\narrows indicate the ho \n sites.ho : heterotropic ossification ; subs : subscapularis ; cp : coracoid process ; un : ulnar \n nerve ; me : medial epicondyle ; olec : olecranon ) . in spite of the medication , he continued to complain of constant pain , limited rom , \n muscle weakness , and impaired hand function .\nrswt was administered to the inferior portion \n of the coracoid process of the left shoulder and the medial epicondyle ( me ) of the left \n elbow using ultrasonographic ( usg ) guidance .\nthe target points of rswt were the ho area that \n could be seen with usg .\n( a ) in case a , bone scan , x - ray , and musculoskeletal ultrasound demonstrate ho in the \n left shoulder and elbow .\n: heterotropic ossification ; subs : subscapularis ; cp : coracoid process ; un : ulnar \n nerve ; me : medial epicondyle ; olec : olecranon\na 52-year - old man with a 6-month history of hypoxic brain injury was admitted to our pmr \n and diagnosed with neurogenic ho of the right elbow ( fig . \n 1 ) .\nrswt was administered to the ho area including the me and olecranon of the \n right elbow using usg guidance .\nmedications were not subsequently required due to a good \n response to rswt . in both cases , rswt was administered using the master plus mp 2000 ( storz , \n tgerwilen , switzerland ) , and the rswt protocol consisted of 3,000 pulses at a frequency of \n 12 hz during each treatment .\nthe intensity level ranged from 25 bars , and it was \n administered 5 times a week for 4 weeks , a total of 20 treatments . during rswt , all other \n treatments , including physical and occupational therapy , were continued as usual .\nboth \n patients were allowed to take previously prescribed oral medications but additional \n analgesics or antispastic medications were not permitted .\npain assessed with the numerical rating scale ( nrs ) , rom , muscle strength assessed with the \n manual muscle test ( mmt ) , a hand evaluation test , and the jebsen - taylor hand function test \n were evaluated prior to each treatment , after treatment , and following 1 month of treatment . \n\npain was reduced from 8 to 0 on the nrs , and the patients remained pain - free \n for 1 month after treatment . in case a , rom of flexion , abduction , adduction , internal rotation , and external rotation \n of the left shoulder and additionally , flexion of the left elbow was improved and \n maintained .\nthe mmt result also showed improvement and the improvement was maintained for 1 \n month ( table 1table 1.range of motion , manual muscle test , hand evaluation test and , jebsen - taylor hand \n function test resultstestcase acase bbeforeafterfollow up upbeforeafterfollow uprange of motion()shoulderflexion 90140 * 145*extension 202020abduction90130 * 130*adduction1020 * 20*internal rotation6070 * 70*external rotation2060 * 60 * elbowflexion 90100 * 100 * 4080 * 85*extensionfullfullfullfullfullfullsupination7070706065 * 80*pronation7060606062 * 80*manual muscle testshoulderflexionfairfair+*fair+*extensionfairgood*good*abductionfairfair+*fair+*horizontal abductionfairfair+*fair+*horizontal adductionfairgood*good*elbow flexionfairgood*good*fairfairfairextensionfairgood*good*fairfairfairhand evaluation test grasp power ( kg)1420 * 18 * 121212lateral pinch ( kg)3.54.5 * 5.5 * 1.52.5 * 2*tripod pinch ( kg)23.0 * 2.5 * 211.5nine - hole pegboard ( sec)30.625.7 * 25.0 * 13865.1 * 58.7*purdue pegboard test ( number ) 1112 * 12 * 03 * 1*jebson - taylor hand function test \n ( sec)writing55.3445.00 * 43.71*ntntntcard turning9.317.87 * 8.76 * 11.0411.076.9*small common object12.1610.59 * 10.15*nt47.3 * 19.5*feeding13.8112.25 * 10.94*ntnt25*stacking checkers7.134.50 * 4.12*ntntntlarge light object ( sec)5.845.914.81 * 8.125.71 * 6.34*large heavy object ( sec)6.945.78 * 4.63 * 8.697.12 * 5.06*follow up period was 4 weeks .\nfunctional testing of hand strength and speed of hand movement showed \n improvements that were maintained at least for 1 month after the end of treatment ( table 1 ) .\nfollow up period was 4 weeks . improved score ; nt : not testable ; \n affected side in case b , right elbow flexion , supination , and pronation were improved , the improvements \n were maintained for 1 month . in contrast to case a , improvement in the mmt result was not \n seen ( table 1 ) . in the hand function test ,\nthe \n strength of the hand and speed of hand movement improved , and these improvements were \n maintained at least for 1 month after the end of treatment ( table 1 ) .\nho is a complicated and significant medical problem characterized by abnormal growth of \n bone in soft tissues , commonly around large joints . in its severe form\n, the condition causes \n pain , limited rom , and loss of function in the affected joint .\nneurogenic ho is associated with injuries to the central nervous \n system , occurs 24 months after a neurological insult , and mainly affects the major synovial \n joints between spastic muscles6 .\nprimary treatment is a combination of gentle passive rom exercises and bisphosphonate \n medication , such as disodium etidronate or nonsteroidal anti - inflammatory drugs .\nsurgical \n excision may be considered for complicated cases , but surgical complications and \n postoperative recurrence are common4 .\neswt has been described in several case reports as a new treatment strategy for neurogenic \n ho , but it has been restricted to the lower extremities7 .\neswt has been shown to promote bone healing in stress fractures , \n avascular necrosis , and delayed and/or bony nonunion , and it has been widely used for \n managing the pain of various musculoskeletal conditions8 .\neswt consists of a sequence of single sonic pulses characterized by \n high peak pressure ( 1001,000 bars ) of short duration ( 0.2 s ) and has a focused pressure \n field with deep penetration depth .\ncompared with eswt , rswt is characterized by 110 bars of pressure of 0.20.5 ms duration \n and has a radial pressure field with shallow penetration depth . despite the physical \n differences , the stimulation effects and therapeutic mechanisms of eswt and rswt are almost \n the same1 . in our cases , pain , rom , muscle strength , and hand function improved although imaging \n studies with radiographs and bone scans showed no changes .\nthis result is consistent with \n previous studies that reported improvement in pain and function without changes in imaging \n studies7 , 8 .\nbased on the results of these studies , it is our opinion that \n imaging findings do not accurately reflect the pain and function caused by neurogenic \n ho .\nthe mechanism of pain reduction with eswt or rswt is not well known and there are several \n hypotheses9 .\neswt or rswt generates \n oscillations in tissue that lead to improvement of microcirculation and metabolic \n activity1 .\nimmediate pain reduction \n after eswt could be the result of a hyperstimulation analgesic effect10 .\nthe improvements observed in rom , mmt , and hand function of the present two cases could be \n associated with pain reduction , since proper management of pain caused by neurogenic ho with \n rswt could have been the cause of the improvements in rom and hand function .\nas reported by previous studies , in our cases , the improvements in pain , rom , mmt , and hand \n function were maintained for 1 month after the rswt treatment7 .\nthe mechanism of the long - term maintenance of the improvements is \n not known but rswt in the early phase of neurogenic ho is effective at preventing \n progression .\nthey were the inferior \n part of the coracoid process of the left shoulder and the me of the left elbow in case a , \n and the me and olecranon of the right elbow in case b. imaging guidance when administering \n rswt for treating neurogenic ho could help to correctly focus on the ho site and avoid the \n other vulnerable structures such as vessels and nerves2 , 10 . in conclusion , rswt improved the pain , rom , and hand function of two patients with upper \n extremity neurogenic ho .\nfurther studies are needed to support these results and to \n understand the mechanism behind the effectiveness of rswt , as well as to devise a protocol \n for rswt for neurogenic ho .", "answer": "[ purpose ] to report the effects of radial extracorporeal shock wave therapy ( rswt ) on \n heterotopic ossification ( ho ) . \n [ subjects and methods ] two cases of neurogenic ho in the \n upper extremity were administered rswt using the master plus mp 2000 ( storz , \n tgerwilen , switzerland ) and ultrasonographic guidance . the rswt protocol consisted of \n 3,000 pulses at a frequency of 12 hz during each treatment . \n the intensity level ranged \n from 25 bars , and it was administered 5 times a week for 4 weeks , a total of 20 \n treatments . \n [ results ] rswt improved pain , range of motion , and hand function in 2 patients \n with neurogenic ho in the upper extremity . \n [ conclusion ] further studies are needed to \n support these results and to understand the mechanism and to devise the protocol of rswt \n for neurogenic ho .", "id": 88} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nafter their biosynthesis at the endoplasmic reticulum , secreted proteins are transported to the golgi complex , where they are post - translationally modified and sorted for secretion , plasma membrane delivery , or delivery to prelysosomes .\nthe golgi contains multiple subcompartments , termed cis ( early ) , medial ( middle ) , and trans ( late ) cisternae ; each of these subcompartments houses different sets of glycosyltransferases and other enzymes .\nproteins enter the golgi at the cis compartment and exit at the trans compartment , but how they move from one cisterna to the next is still being determined .\ntwo possible models are widely discussed [ 1 - 3 ] . according to the cisternal maturation ( or progression ) model ,\ncargo remains in a given compartment and different enzymes arrive there to convert a cis cisterna into a medial one or a medial cisterna into a trans cisterna .\nalternatively , cargo moves from one golgi compartment to the next , encountering different enzymes in each subsequent compartment until it reaches the trans cisterna , where it is then sorted into carriers bound for post - golgi destinations .\nthis second class of model could use vesicles to transport cargo from one compartment to the next or compartment - connecting tubules through which cargo could pass .\nconversion of one golgi compartment into another by high - resolution , live cell video microscopy .\na limitation of those studies is that one of the compartment markers that was monitored is a peripheral membrane protein that is likely to reversibly bind to and release from the golgi surface .\nthe situation may be more complex in mammalian cells , where golgi cisternae are stacked tightly together , unlike yeast ; it is hard to imagine a single cisterna moving from one side of the well - stacked structure to the other .\nnevertheless , large procollagen cargo traverses the golgi without ever leaving a cisterna , in support of a maturation model . to complicate matters ,\nmembrane tubules have been detected between golgi cisternae under conditions of active secretion ; this scenario would permit cargo movement from one side of the stack to the next without maturation or vesicle transfer .\nimportant new clues to how golgi compartments might mature come from a study of golgi - localized , ras - related , rab family gtpases in yeast .\nrab gtpases are localized to different membrane compartments and catalyze the formation of functionally distinct , membrane microdomains that are important for transport vesicle formation , vesicle motility , and vesicle ( or compartment ) docking and fusion .\nrab gtpases help early endosomes mature into later endosomes by a process called rab conversion .\nthe early endosomal rab5 protein recruits a specific guanine nucleotide exchange factor ( gef ) that activates rab7 .\nrab7 then recruits rab7-specific effectors to that compartment , thereby converting an early endosome into a late endosome .\nthis type of rab cascade ( figure 1b ) was first described for a yeast golgi rab , ypt32p , recruiting the gef for the subsequent acting sec4p rab .\n( a ) endoplasmic reticulum , golgi , and endosome membranes are capable of homotypic fusion and fission .\n( b ) rab cascades occur when sequentially acting rabs recruit guanine nucleotide exchange factors ( gefs ) and gtpase - activating proteins ( gaps ) to membranes .\nraba recruits a gef that will convert the subsequent acting rab to its active form .\nrabb can then recruit a gap that will inactive the previous acting rab , thereby removing it from the newly formed , second compartment .\nrivera - molina and novick have now used live cell video microscopy to detect rab conversion at the yeast golgi : they see compartments containing the early golgi rab , ypt1p , convert into a compartment containing the late golgi rab , ypt32p .\n( although the light microscopy method employed could not resolve structures smaller than about 200 nm , the images were nevertheless highly compelling . )\nthe process involves the recruitment of ypt32p by the gtpase - activating protein ( gap ) that inactivates ypt1p : gyp1p . upon inactivation\n, ypt1p becomes a substrate for removal from membranes by another protein , gdi ( gdp - dissociation inhibitor ) .\nthe removal of rabs from the membranes makes this work subject to one of the same limitations of the previous studies ; nevertheless , these markers permitted the authors to detect an important molecular transformation .\nthe data provide a direct molecular mechanism for compartment inter - conversion at the golgi , reminiscent of maturation in the endocytic pathway .\ngolgi compartments were seen to be dynamic , undergoing a certain amount of fission and fusion . in some cases ( 30% )\n, a ypt32p compartment appeared to fuse to a ypt1p compartment to yield a mixed compartment or a mixed compartment appeared to undergo segregation and fission to yield separate ypt1p and ypt32p compartments .\nwhat this means is that , yes , yeast golgi compartments undergo apparent maturation by rab conversion , and at the same time , cargo may get the \nfast track from one compartment to the next by intermittent cisternal fusion and fission events ( figure 2a , b ) . importantly , although a compartment will seem to mature , it is actually forming from a stable predecessor .\nearly golgi has the capacity to fuse with other early golgi cisternae and so on .\nfission is favored in the absence of microtubules or when golgin proteins are depleted from cells .\nglycosyltransferases are localized to cis ( red ) , medial ( yellow ) , and trans ( orange ) golgi compartments but rarely have a perfectly sharp distribution .\nthus , for example , cis - golgi homotypic fusion events can occur with another cis compartment ( step 1 ) or perhaps a medial ( yellow ) compartment ( or both ) .\nsimilarly , a medial cisterna may be able to fuse with a trans cisterna ( orange ) . in this manner\n, a large cargo may be able to encounter all golgi - processing enzymes without entering a transport vesicle , indicated by fusion steps ( arrows ) 1 , 2 , and then 3 .\nthe ability of golgi cisternae to undergo fission and fusion has been known since the 1970s : simple , nocodazole - triggered depolymerization of microtubules causes the mammalian golgi to fragment into mini - stacks that disperse throughout the cytoplasm , and drug washout leads to rapid stack reassembly ( figure 2a ) .\nthis indicates that the golgi is capable of fission as soon as microtubules are lost and of fusion with itself as soon as microtubules repolymerize .\ncompartment collisions likely enhance fusion , and cytoskeletal motor proteins that decorate the golgi and connect it to both microtubules and actin cables are sure to contribute to both fusion and fission events , as is true in the endocytic pathway ( figure 1a , c ) . are intercisternal fusion / fission connections required for membrane traffic ?\ntransport is only partially blocked in nocodazole - treated cells and this condition favors stack fission .\nbut homotypic fission and fusion are likely much more prevalent than previously anticipated because cellular depletion of any one of many different golgi proteins ( golgins ) generates mini - stacks that are clustered near the microtubule - organizing center .\nsuch transient fusion and fission could yield the tubules that have been detected in electron micrographs of mammalian cell golgi complexes .\nfission and fusion would make it possible to accommodate extra - large cargoes , such as collagen , that are too big to fit into conventional transport vesicles .\nas is well established for the endocytic pathway , rab gtpases would define specific subdomains and retain specific golgi enzyme subsets there .\ncompartments would be defined by their distinct rab gtpases , and adjacent cisternae might fuse at some frequency that allows cargoes to encounter sequentially acting , processing enzymes . in a mixed compartment , rab gefs and gaps would segregate individual rabs into separate regions that would be segregated upon the simple action of a membrane - associated , cytoskeletal motor protein to drive fission .\norder within the stack would be maintained by the relationship between specific rabs and their cognate activators ( gefs ) and inactivators ( gaps ) , which are designed to permit rabs to function in a sequential cascade .\nindeed , the proteins that stack the cisternae may use a rab cascade to achieve their position in the stack . at the trans golgi\n, rabs would also initiate the process by which specific cargoes are collected into distinct transport carriers and delivered to their final destinations .\nvalidation and clarification of this model will require defining which rabs build which specific golgi enzyme microdomains and determining the specific molecular interactions that permit fission , fusion , and enzyme organization .\nvesicles are likely to be involved in golgi transport : we know that cop - i - coated vesicles collect kdel receptors for delivery back to the endoplasmic reticulum ; in this case , we can postulate that such vesicles bud from a rab gtpase - organized , functional membrane microdomain .\nthe same proteins that drive vesicle targeting and fusion may also participate in cisternal docking and fusion to permit protein transport across this central cellular compartment .\nthe mechanism by which depletion of any one of at least 10 different golgin proteins leads to mini - stack formation will likely tell us much about how proteins move through the mammalian golgi stack .", "answer": "the golgi complex is a central processing station for proteins traversing the secretory pathway , yet we are still learning how this compartment is constructed and how cargo moves through it . \n recent experiments suggest a key role for ras - like rab gtpases and provide important new ideas for how the golgi may function .", "id": 89} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nGromologist: a Gromacs-Oriented Utility Library for Structure and Topology Manipulation\n\nPaper sections:\nIntroduction\nMolecular dynamics (MD) simulations are a cornerstone of modern-day computational chemistry and biology, and in the last 40 years a range of general-purpose codes have been developed to make simulations more reproducible and accessible to the community [1][2][3][4][5][6][7]. Although the preparation of typical biomacromolecular systems, e.g. proteins, lipid membranes or nucleic acids containing standard residues, has become extremely streamlined and automated [8][9][10], the corresponding topology files -containing a full description of the system's connectivity and energetics -can be unreadable and not amenable to simple manual manipulation. As a result, any non-automated departure from these standards, such as removing atoms or adding bonds, can become a painstakingly complex process, in particular for novice users not aware of nuances and caveats of these fixed file formats.
To deal with these routine but non-standard tasks, high-level utility libraries are needed that can accommodate the increasing complexity of inputs and dynamically respond to popular requests from the community. One notable example of such a library, Parmed, has already been incorporated into Amber and contains many OpenMM-specific functions [11], but its primary goal is to provide easy access to general properties and allow for smooth interconversion between standard file formats. Another one, pmx, serves to prepare hybrid topologies for \"alchemical\" simulations and the analysis of thus obtained results [12]. Many routine tasks, though, are not covered by any popular library, leaving plenty of room for new developments.
In an attempt to fill that gap, we present Gromologist, a Pythonic utility library oriented at custom manipulation of Gromacs topologies. For many years now, Gromacs has been not only the most broadly used but also one of the fastest-growing MD engines in the field of molecular simulations [13,1] and has a well-established user base, whichcombined with the ease of format interconversion allowed by other tools -makes Gromologist a broadly applicable tool for all types of non-standard operations including, but not limited to, adding and removing atoms and bonds, introducing amino acid mutations in both the structure and topology, checking and listing force field parameter compatibilities, looking for mismatches between structures and topologies, merging files, manipulating alchemical states, modifying force field types or combination rules, parameter optimization or automated editing of structures. In addition, we maintain a strict zero-dependency policy (except for a few very specific features), so that the library is conveniently lightweight and can be easily installed with any modern Python distributions without causing dependency conflicts.
\n\nFeatures Topology manipulation\nTo handle Gromacs topologies, Gromologist implements a hierarchical representation of sections, subsections and entries. Sections represent high-level abstractions, such as individual molecule definitions, force field parameter sets or headers/footers. Subsections correspond to individual fragments of the topology file, delimited with the [ subsection name ] syntax, and directly handle most operations. Entries correspond to individual lines and provide a low-level access to all key features of the contents of a topology.
Splitting and merging. By default, topologies are saved as a single standalone file, including all .itp files referenced therein, but splitting to individual .itp is also supported. If needed, files can be made lightweight by keeping (a) only molecules listed in the [ system ] subsection and/or (b) only parameters used by the system.
Bonds and atoms. Primitive operations on topologies include adding, removing or swapping atoms in molecules while preserving a correct numbering scheme across all sections. Adding or removing bonds is also supported, including new bonds between two molecules, in which case the two become merged into a single molecule entry, and all new bonded terms (pairs, angles, dihedrals) are automatically identified and added, while existing ones are preserved and renumbered correctly. This allows for easy creation of chemical adducts or cyclic molecules, as well as editing of protonation states or simple chemical modifications without the need of extending the basic residue library (.rtp/.hdb files). Another heavily requested feature was the automated introduction of ,,special bonds\" -disulfides and transition metal coordination bonds -that are not always correctly guessed by default Gromacs tools. Finally, Gromologist also provides a low-level interface for the mutation library, and can be easily incorporated into custom modification workflows.
Mutations. In this vein, a mutations module allows to introduce standard amino acid mutations to the topology without the need to go through the full process of topology generation. This has proven particularly useful in the study of heavily glycosylated systems, such as the SARS-CoV-2 Spike [14], where ready-made topologies and systems were often shared publicly but introducing even minor changes (such as a point mutation) would entail going through the same complicated server-based pipeline, risking introducing additional errors at this stage. This idea is also extended to protonation states, so that individual titratable residues can be protonated or deprotonated easily and in a consistent manner. As long as standard atom name conventions are followed, the mutation module is force-field agnostic, and the user can point to a specific .rtp file containing the respective residue definitions.
Alchemistry. Another set of utilities is related to the management of alchemical states. Gromologist can add or remove selected alchemical states, or swap them -a useful feature e.g. for the equilibration of B-states that helps avoid the computational overhead associated with the use of the free energy code.
Force fields. Finally, some features are meant to facilitate force field development and the implementation of selected methods such as solute tempering (REST2) [15]. These include the possibility of automatically cloning types along with all their bonded interaction parameters and renaming all selected atoms to the new type, or by automatically adding NBFIX-type modifications just by specifying the deviation from the standard Lorentz-Berthelot rules [16,17]. An additional module implements a generic strategy for multiple dihedral fitting to QM data, akin to that available in the FFTK module of VMD for NAMD topologies [18].
\n\nStructure manipulation\nThe structure module can deal with both PDB and GRO files, interconverting between them when necessary. Common operations include constructing new atoms from existing ones, interpolating between structures, atom/residue renumbering according to custom rules or generation of virtual sites, e.g. upgrading 3-point water molecules to 4-point ones.
\n\n2/5\nIn addition, many often-required features of the PDB files can be filled in automatically. Chain assignment, an information typically lost in PDB to GRO conversion can be inferred based on a simple distance criterion, similarly to the CONECT entries required by some analysis programs. Elements can be inferred from atom names, and beta-factors can be set to reflect external data sets, including an option to smooth the values out spatially.
To assist with these operations, Gromologist implements a robust selection language akin to that of VMD [19], allowing for logical operations, selections \"within X of Y\", and a number of predefined molecule classes such as \"protein\", \"nucleic\" or \"solvent\". Periodic boundary condition (PBC) treatment is also implemented for any generalized triclinic box.
\n\nSimultaneous processing of topology and structure\nIn Gromologist, topologies can be matched with a compatible structure, so that where relevant, topology operations can be simultaneously performed on the structure attribute (and vice versa), facilitating the work with simulation-ready systems, and fully leveraging the information available in both files. Examples of such procedures include atom addition/removal, or introduction of mutations. When a topology is available, chain assignment can be made using molecule definitions therein. Moreover, when Gromacs often only indicates an unspecified mismatch between e.g. the number of atoms in structure and topology, Gromologist provides a specific list of all unmatched atom names, facilitating the identification of missing atoms or residues in either one.
\n\nChecking and printing\nThe last area of applications of Gromologist covers extracting information about the topologies and structures, or making it better visible to the user. On the most basic level, one can list molecules in the system, atoms in the molecule, as well as selected bonded terms (bonds, 1-4 pairs, angles, dihedrals) using atom names or atom types. Charges and masses of both the whole system and individual molecules are easy-to-access attributes. For a protein or a nucleic acid structure, the sequence can be printed chain by chain, and per-residue missing atoms identified, helping identify cases in which residues have to be rebuilt. Gradually diagnostic functions are being incorporated to quickly identify structural issues prior to simulation, like one currently allowing for validation of all chiral centres in a protein.
When required, atom names can be explicitly stated in the comments of bonded interaction entries to facilitate debugging, and numerical values of the parameters can be explicitly included in the topology. In the same vein, fields set using the define syntax can be set to their explicit values. Parameters whose numerical definitions are missing can also be identified with a single function call.
\n\nDependencies\nTo be applicable as broadly as possible, Gromologist uses no dependencies other than base Python libraries. Although a few optional features, such as smoothing of beta-factors or dihedral optimization, do require numpy and scipy, these make up extremely rare use cases and therefore do not form part of the official dependency list.
\n\nOutlook\nGiven the existing set of capabilities, Gromologist is becoming an easily extensible platform for the introduction of further convenience functions, editing tools and workflows. Further development of the platform could benefit the Gromacs community by rapidly implementing utilities tailored to new or popular protocols, and a closer collaboration with the Gromacs development team is expected to directly address these issues. Moreover, extensive testing and some code reorganization will be required to ensure that the library covers all features supported by Gromacs, including more cryptic ones. In the long run, however, we expect Gromologist to become a stable element of the Gromacs environment and a valuable contribution to the broad simulation community.
3/5
", "answer": "Despite the increasing automation of workflows for the preparation of systems for molecular dynamics simulations, the custom editing of molecular topologies to accommodate non-standard modifications remains a daunting task even for experienced users. To alleviate this issue, we created Gromologist, a utility library that provides the simulation community with a toolbox of primitive operations, as well as useful repetitive procedures identified during years of research. The library has been developed in response to users' feedback, and will continue to grow to include more use cases, thorough automatic testing and support for a broader spectrum of rare features. The program is available at gitlab.com/KomBioMol/gromologist and via Python's pip.", "id": 90} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthyroid incidentalomas are newly detected thyroid nodules , discovered during a computed tomography ( ct ) , magnetic resonance imaging ( mri ) , ultrasound ( us ) , or positron emission tomography ( pet ) exam for nonthyroid diseases .\nfocal type is defined as an area of uptake of 2-fluorodeoxyglucose ( fdg ) in less than one lobe , whereas diffuse type is fdg uptake in the entire thyroid gland .\nthere are guidelines for managing palpable thyroid nodules but there are no such guidelines for nonpalpable nodules .\nfdg - pet has a reported sensitivity of 7590% and a specificity of 90% for detecting thyroid malignancies .\nwhole body fdg - pet / ct combines the technology of whole body ct scan with fdg uptake localization to assess glucose utilization rates .\nthe vast majority of solid tumors have an enhanced glycolytic rate , and they are therefore amenable of being imaged with fdg - pet .\nfdg - pet has become the standard of practice for staging , restaging , and assessment of therapy response in a variety of malignant solid tumors .\nnormal thyroid gland shows very low fdg uptake , and some data suggest that a moderate diffuse uptake can represent a normal variant . however , fdg has high accumulation in tumors because of increased glucose transport and glycolysis .\nbenign diseases of the thyroid such as graves ' disease and thyroiditis can have high standard uptake values ( suv ) because of increased blood flow , increased glucose metabolism , autoimmune response by lymphocytes , and inflammation .\ntherefore , areas with high fdg uptake can be nonspecific and can range from benign processes to malignant neoplasms .\nthyroid nodules have different morphologic appearances , and they can be seen as diffuse or focused lesions on the pet / ct .\nus is usually the first step in the management of thyroid abnormalities found in physical and laboratory exams .\nthe overall incidence of thyroid incidentalomas is on the rise with 2.4 times increase in the last decade .\nbased on the pet / ct alone , definite diagnosis can not be made since there are no established criteria to diagnose benign or malignant incidentalomas .\ncurrent practice is to biopsy all nodules > 1 cm and all nodules < 1 cm with risk factors for malignancy .\nthis study also aims to assess the value of pet / ct as a screening tool to screen for thyroid incidentalomas .\nthere is no report on the prevalence of pet / ct thyroid incidentalomas in the general population . yet ,\nthyroid incidentalomas are quite common , and their prevalence depends on the population studied , region or country where the study was conducted , and the diagnostic methods used .\nwe performed a retrospective analysis of all whole body fdg - pet / ct done at our institution between 1/1/2000 and 8/20/2008 ( figure 1 ) .\nan inclusion criteria was that the lesions were not visible or palpable during routine clinical exam .\nwe excluded from our study all cases with prior histories of thyroid neoplasms and thyroidectomies or any type of thyroid surgery .\na total of 156 patients who had abnormal fdg uptake were further selected for secondary analysis . from this group ,\nunivariate one - way analysis of variance ( anova ) was performed to characterize differences between segments classified according to the results of diagnostic methods . a p value of < 0.05 was considered statistically significant .\nin this study , only 40 out of 156 incidentalomas ( 25.6% ) had biopsies .\nthere are lesions with low , hyperdense , and a mixture of low and high attenuations .\nour results show no correlation between the size of the lesion and the suv value .\nthere are papers that show the correlation between size and suv value while some show no correlation . in the group of cancerous incidentalomas , there are 6 males ( mean age 53.3 , age range 3378 ) and 9 females ( mean age 56.2 , age range 3873 ) . for the group with benign incidentalomas , there are 4 males ( mean age 76.5 , age range 6983 ) and 21 females ( mean age 59.1 , age range 3986 ) .\n14 out of 15 ( 93% ) malignant lesions have focal uptake , and the remaining 1 has diffuse uptake .\nthis finding agrees with prior studies in that focal uptake lesions have > 30% increase in malignancy rates compared to diffuse uptake lesions . among cancerous nodules ,\nthe highest suv value is 9.9 and the lowest is 2.5 ( figure 2 ) , and for the benign lesions , the highest is 46 and the lowest is 0.8 . from the 40 biopsy reports , there are 15 cancerous nodules , corresponding to about 38% .\nthere are 11 papillary carcinomas ( 6 right lobe , 3 left lobe , 2 both lobes ) , 1 follicular carcinoma ( left lobe ) , 1 anaplastic carcinoma ( right lobe ) , 1 adenocarcinoma from the breast primary ( left lobe ) , and 1 metastasis of unknown origin ( right lobe ) .\namong benign incidentalomas , there are 2 nonspecific benign lesions ( 1 left lobe and 1 right lobe ) , 18 colloid lesions ( 10 left lobe and 8 right lobe ) , 1 chronic lymphocytic thyroiditis ( right lobe ) , 3 follicular adenomas ( 2 left lobe and 1 right lobe ) , and 1 hurthle cell lesion ( right lobe ) .\ngenerally , incidentalomas found in males at young age carry a risk of being malignant .\nwe also find that incidentalomas are far more common in females than males , and this is in agreement with other studies .\nframingham population - based study reported the thyroid nodule prevalence of 6.4% for females versus 1.6% for males .\nthe average size of nodules in the malignant group ( n = 12 ) is 2.0 cm ( range 0.66 cm ) , and that in the benign group ( n = 20 ) is 1.4 cm ( range 0.22.4 cm ) .\nthe graphical representation of sizes in figure 3 shows that the majority of sizes of benign and malignant incidentalomas are in the same range ( i.e. , below 3 cm ) with only 2 of the lesions in the malignant group ( 5 cm and 6 cm , resp . ) outside this range .\nwe can not safely conclude that small nodules are benign and large nodules are cancerous , and there is no agreement yet on the cutoff value of the size of the lesion to warrant further workup .\nadequate samples are difficult to obtain from lesions < 8 mm . on the other hand\n, studies have shown that cancer prevalence for lesions < 1 and > 1 cm is the same , and so we must take the other risk factors into consideration besides the size . moreover ,\npapini et al . who examined us features of thyroid nodules also found no correlation between malignancy and the dimensions of the lesion or the multinodularity .\nattenuation is a feature of ct , and low attenuation means that a particular area is less intense than the surrounding .\nall of the malignant nodules confirmed by biopsy have low attenuation , with the exception of two which have a mixture of high and low attenuation . for this study ,\nsome studies associate low attenuation with malignancy while some suggest high attenuation for malignancy [ 4 , 6 ] .\ndiffuse fdg uptake is often due to hypothyroidism or thyroiditis , especially hashimoto 's or autoimmune thyroiditis .\none study reported higher likelihood of cancer when the average suv is greater than 5.69 but most other studies can not find a correlation between suv and malignancy [ 9 , 19 ] . in our study ,\nthe average suv value of the malignant group ( n = 15 ) is 5.5 , and that of the benign group ( n = 25 ) is 7.2 . as a result ,\nconsidering these information , we can not set a threshold suv value for malignant lesions .\nour prevalence of 38% falls within the range of 1850% reported in the literature for prevalence of malignancy among incidentalomas . in our study , most of the malignant incidentalomas are primary thyroid malignancies , and this is similar to other studies where most cancerous incidentalomas are thyroid primary .\npapillary carcinomas are most common , and the majority of them occur as right lobe lesions\n. prevalence of incidentalomas found by pet / ct at our institution is 1.84% , which is within the range of 1.24.3% reported by liu .\nthe results of our study are compared to studies done on incidentalomas at other institutions ( table 3).the investigations at various hospitals mentioned in table 3 reflect different study designs , patient populations , and institutional practices .\nthe prevalence of incidentalomas range from 1.1% to 7% and the prevalence of malignancy among incidentalomas ranges from 14% to 66% .\na new thyroid nodule appears at the rate of 0.08% per year in the general population , and the incidence of thyroid malignancy is 0.0040.1% per year .\nnot surprisingly , the incidence and prevalence of thyroid cancer in the patient population we see at the nuclear medicine department at ucsf is much higher than the general population .\nif we perform pet / ct scans to screen for incidentalomas in the general population , it will increase the health care costs with little benefit to the patients .\nthe cost of pet / ct far outweighs the reduced mortality associated with early diagnosis of thyroid cancers . a paper by ohba et al . , who prospectively followed patients for 3 years , mentioned that repeated fdg - pet to follow up patients with thyroid nodules is ineffective .\ndiffuse - type incidentalomas with the absence of risk factors can be managed by physician visits , lab tests , and monitoring with us .\nyet , we can not rule out malignancy based on the diffuse pattern alone because the diffuse uptake can mask the focal lesions .\none of the limitations of our study is that out of 156 abnormal pet / ct thyroid exams , only 40 had biopsy reports .\nthe prevalence of malignancy among incidentalomas may be different from the current one if all underwent biopsy .\nwe must be aware that pet / ct can not detect small lesions such as micropapillary thyroid carcinomas which can have normal or low suv uptake .\nour data suggest that focal fdg uptake representing incidentalomas should be followed by pathologic diagnosis , especially in those with chronic conditions or known diagnosis of a solid tumor .\nthis study did not support the idea for using pet / ct to screen the general population for incidentalomas .", "answer": "objectives . to determine the prevalence of incidentalomas in a patient population with no known thyroid malignancy who underwent whole body fdg - pet / ct for staging or restaging of neoplasia . \n the additional aim of the study was to evaluate the feasibility of using petct as a screening tool for malignant thyroid incidentalomas . \n methods . \n retrospective review of medical records of all the thyroid exams done at our institution between january 1 , 2000 and august 20 , 2008 . \n we made a criterion of pet / ct as the primary method of detection of incidentalomas . \n results . from a total of 8464 thyroid exams , \n 156 incidentalomas were found and 40 incidentalomas underwent anatomopathology analysis , which was used as gold standard . \n chi - square analysis was used to analyze the data . \n there is no significant association between suv value and the prevalence of incidentalomas . discussion . from january 1 , 2000 to august 20 , 2008 \n , incidentalomas have a prevalence of 1.84% at our institution . \n 38% of the incidentalomas that were biopsied were characterized as representing malignant tumors . conclusion . \n focal , abnormal fdg uptake representing incidentalomas must be followed up with biopsies . \n it is impractical to use pet / ct as a screening tool to detect incidentalomas for the general population but it must be done in patients with history of any type of cancer .", "id": 91} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe study was approved by the joint ethics committee of the institute of neurology and the national hospital for neurology and neurosurgery , london , uk .\nall structural and functional scans at time 1 and time 2 were acquired from the same siemens 1.5 t sonata mri scanner ( siemens medical systems , erlangen , germany ) .\nthe structural images were acquired using a t1-weighted modified driven equilibrium fourier transform sequence with 176 sagittal partitions and an image matrix of 256 224 , yielding a final resolution of 1 mm [ repetition time / echo time / inversion time = 12.24 ms / 3.56 ms / 530 ms ] .\npre - processing of 66 structural images ( 33 participants 2 time points ) used spm8 ( http://www.fil.ion.ucl.ac.uk/spm ) with the dartel toolbox to segment and spatially normalize the brains into the same template ; with and without modulation .\nmodulated images incorporate a measure of local brain volume while unmodulated images , used with proportional scaling to correct for global grey matter , provide a measure of regional grey matter density .\nprevious studies have shown the correlations between brain structure and cognitive ability are better detected by grey matter density .\nimages were smoothed using an 8 mm isotropic gaussian kernel at full width half maximum ( fwhm ) . the relationship between change in iq and change in brain structure\nwas investigated by entering the appropriate pre - processed images ( modulated or unmodulated grey or white matter ) into within subjects paired t - tests , with change in iq ( viq , piq or fsiq ) and year of scan as covariates . the degree to which time 2 iq was predicted by changes in brain structure\nwas investigated in a hierarchical regression analysis with time 1 iq entered before change in brain structure .\ndetails of the functional imaging paradigm have been reported elsewhere and are summarised in supplementary information ) .", "answer": "intelligence quotient ( iq ) is a standardized measure of intellectual ability that taps a wide range of cognitive skills1 . across life span \n , iq is generally considered to be stable with scores at one time point used to predict educational achievement and employment prospects in later years1 . \n neuro - imaging allows us to test whether unexpected longitudinal fluctuations in measured iq are related to brain development . \n here we show that verbal and nonverbal iq can rise or fall in the teenage years , with these changes in performance validated by their close correlation with changes in local brain structure . \n a combination of structural and functional imaging showed that verbal iq changed with grey matter in an area that was activated by speech , while nonverbal iq changed with grey matter in an area that was activated by finger movements . by using longitudinal assessments of the same individuals \n , we eschewed the many sources of variation in brain structure that confound cross sectional studies . \n this allowed us to dissociate neural markers for verbal and nonverbal iq and to show that these general abilities are closely linked to the sensorimotor skills involved in learning . \n more generally , our results emphasize the possibility that an individual s intellectual capacity relative to their peers can weaken or strengthen in the teenage years . \n this would be encouraging to those whose intellectual potential may improve ; and a warning that early achievers may not maintain their potential .", "id": 92} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen fibrosarcoma is diagnosed during the early years of life , it is called congenital infantile fibrosarcoma ( cif ) , representing less than 1% of all pediatric malignant tumors ( 1 , 2 ) .\nin contrast with adult fibrosarcoma , infantile fibrosarcoma ( if ) rarely exhibits distant metastasis and has a good prognosis ; greater than 90% of patients may be cured with appropriate management .\nthe tumor usually occurs in soft tissues of the extremities and is often asymptomatic . in such cases ,\nrarely , if may occur in the gastrointestinal tract ; a few cases of gastrointestinal fibrosarcoma have been reported in the literature .\nnecrotizing enterocolitis ( nec ) , which is a primary intestinal wall pathology , has been cited as the major cause of pneumoperitoneum in most published literatures ( 3 , 4 ) .\nhowever some conditions , not affected by a primary pathology of intestinal wall itself ( e.g. intestinal atresia , stenosis , meconium ileus , colonic aganglionosis or volvulus ) , may lead to neonatal pneumoperitoneum .\nthis case was a pneumoperitoneum not associated with a nec also . in this report , we present an extraordinary case of cif of the sigmoid colon causing pneumoperitoneum in a newborn baby .\na 2-day - old korean boy , delivered at 37 weeks by cesarean section owing to fetal bradycardia , with a birth weight of 3,420 g , was referred to the neonatal intensive care unit in pusan national university children 's hospital because of abdominal distension and free air in the peritoneal cavity at may 1st , 2011 .\na plain abdominal radiograph showed normal air - filled loops of bowel ; however a large amount of free air occupied the central portion of the abdomen ( fig .\n1 ) . the patient underwent an emergency laparotomy on the day of admission to the neonatal intensive care unit . a large amount of bile - stained\na round mass , about 5 cm in diameter , was observed in the left lower abdominal cavity , and it seemed to wrap around a loop of sigmoid colon ( fig .\npathologic analysis report described an infantile fibrosarcoma , measuring about 4.7 2.8 cm , involving mainly the submucosa and muscularis propria with an infiltrative growth pattern ( fig .\nthe immunohistochemical stain of the tumor was positive for vimentin and sma , and negative for h - caldesmon , s-100 , cd34 , c - kit , desmin , and alk-1 ( fig .\n4 ) . the ki-67 proliferation index was 20% . because complete surgical resection was performed and the surgical resection margins were free tumor , the patient was observed without adjuvant therapy .\nfibrosarcoma is a tumor that arising from mesenchymal cells and composed of malignant fibroblasts within a collagen background . after infantile fibrosarcoma\nfirst recognized in 1962 ( 5 ) , it has been generally studied . congenital infantile fibrosarcoma ( cif ) is a very rare type of nonrhabdomyosarcoma soft - tissue sarcomas , usually occurring in the 1st year of life , with approximately 40% of lesions present at birth and more than 80% diagnosed within 1 yr ( 6 ) .\nit accounts for 5%-10% of all soft - tissue sarcomas in infants younger than 1 yr and is slightly more common in boys ( 7 , 8) .\nin contrast with adult fibrosarcoma , infantile fibrosarcoma ( if ) is considered a low - grade malignant tumor and carries an excellent prognosis , with survival rates of 80%-90% ( 9 ) . if is usually located in subcutaneous tissues at various anatomic sites , most frequently involving the extremities and the axial regions . especially in older children , if less frequently involves the trunk , head and neck ( 6 ) .\nthe manifestation of infantile fibrosarcoma in the reported cases is generally a painless swelling , exhibiting steady growth .\nhowever , it may rarely involve the retroperitoneum , mesentery , mouth , presacral region , lung , or gastrointestinal tract .\na few cases have been reported recently about if involving the gastrointestinal tract ( e.g. , the duodenum , jejunum , ileum , and hepatic and splenic flexures of the colon ( 10 - 12 ) .\nintestinal obstruction or meconium peritonitis due to bowel perforation was the primary manifestation in the reported cases involving intestine . in our patient , pneumoperitoneum was the presenting problem , but there were no gross findings at surgery implying a definite perforation of the colon or rupture of the mass ; neither was there any ischemic change or obstruction , or apparent necrosis of the tumor on histologic examination .\nwe found no obvious explanation for the large amount of free - air in the peritoneal cavity seen on radiologic examination prior to surgery ; we assume that a sealed - off microperforation was responsible for the condition .\npneumoperitoneum in neonates accounts for about 1% of total admission at a neonatal intensive care unit .\nmost cases occur in relation to a primary intestinal wall pathology such as necrotizing enterocolitis ; however , pneumoperitoneum may rarely be associated with intestinal atresia , stenosis , meconium ileus , colonic aganglionosis , or volvulus .\nit is necessary to distinguish if from other stromal tumors , particularly in cases involving the gastrointestinal tract .\n. molecular biological analysis may be useful when identifying the presence of specific transcription errors , e.g. , the evt6-ntrk3 translocation , but it is not always used ( 6 , 9 , 11 )\n. surgical excision remains the principal component of treatment , showing a good result when complete resection with tumor - free margins is achieved .\nthere is no defined role for adjuvant chemotherapy or radiotherapy after complete surgical excision ( 9 , 13 ) .\nthe prognosis is generally favorable with more than 90% long - term survival ( 9 ) . in our patient\n, we could not identify any evidence of local recurrence or distant metastasis during a 1-yr follow - up period . in conclusion ,\ncif of the sigmoid colon is a rare soft tissue tumor , with a favorable outcome likely after appropriate surgical resection .\nit may present with bowel perforation in the early neonatal period ; therefore a neonatal pneumoperitoneum not related to necrotizing enterocolitis requires attention for management .", "answer": "congenital infantile fibrosarcoma ( cif ) is a rare soft - tissue tumor in the pediatric age group and seldom involves the gastrointestinal tract . \n a 2-day - old boy was transferred to our hospital with a pneumpoperitoneum . \n after emergency operation , we could find a solid mass wrapping around a sigmoid colon and performed a segmental resection of sigmoid colon including a mass . \n histopathologic examination showed an infantile fibrosarcoma origining from the muscular layer of colon . \n the baby was discharged on the 17th hospital day and followed for 1 yr without recurrence .", "id": 93} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npostoperative pulmonary complications are found to be associated with increased morbidity and mortality following abdominal surgeries .\nthey also lead to additional health cost and prolonged length of hospital stay . according to the findings reported in an australian study , postoperative pulmonary complications are 13% prevalent and significantly prolong length of hospital stay .\nhowever , various rates of pulmonary complications had been reported in the literature due to lack of proper criteria for pulmonary complications .\navailable evidences suggest that early postoperative mobilization following abdominal surgery contributes to improved lung volume which eventually reduces incidences of postoperative pulmonary complications [ 5 , 6 ] .\npreoperative counseling regarding hospital stay and patient 's role in recovery has proven to reduce anxiety , reduce length of stay , and have better compliance with postoperative care plan including early mobilization .\neventually , preoperative counseling may contribute towards early mobilization that can reduce postoperative pulmonary complications following abdominal surgery .\ncounseling regarding surgical procedures is commonly employed at every setup but less importance is given to additional counseling regarding postoperative management .\nthis study aims at evaluating the effect of preoperative counseling regarding postoperative mobilization and its impact on reducing pulmonary complications in a developing world .\nthe randomized control trial was conducted at the department of general surgery of a tertiary care hospital of karachi , pakistan , from september 2012 to march 2013 .\nparticipants were recruited from outpatient clinic as well as from emergency department of the hospital .\nminimally invasive surgeries and patients whose score was > 2 on the american society of anesthesiologist ( asa ) scale were excluded .\nmoreover , patients who were smokers and had abnormal findings on x - ray were also excluded .\nevery second patient who visited selected study setting was recruited in group i , whereas others were kept in group ii .\ngroup i received informed consent regarding surgical procedure as well as counseling related to early postoperative mobilization and its impact on surgical outcome , whereas group ii received information regarding surgical procedure only . to reduce biasness , senior residents who were not part of the study conducted these counseling sessions .\nexplanation was given about nature of study , rights of study participants , privacy and confidentiality of participants , and rights of withdrawal from study .\nin addition , history of previous illness , comorbidity , and any barrier to early postoperative mobilization were assessed .\nboth groups received counseling regarding nature of surgery and its complications , what to expect during hospitalization , postoperative pain management , and possible complications associated with surgery and anesthesia , whereas group i received additional information regarding postoperative mobilization and its impact .\npatients were encouraged and assisted to mobilize once they were fully awake , with stable blood pressure and pulse , no dyspnea on rest , and pain score of < 8 on visual analogue scale .\nthe time at which surgery ended and the time when patient first got out of the bed ( bed to chair ) were recorded .\nin addition , time from end of surgery to first mobilization of > 10 minutes was also recorded .\npatients who had prolonged duration of surgery and who were smokers underwent chest physiotherapy and incentive spirometry with the help of physiotherapy staff .\npostoperative pulmonary complications following abdominal surgery were assessed via criteria of scholes et al . \npostoperative pulmonary complications are as follows.chest x - ray showing collapsed lung or consolidation.increased body temperature > 38c for more than one consecutive postoperative day.sputum culture providing evidence of infection.productive yellow or greenish sputum.unexplained increased white blood cell count.abnormal breath sound on auscultation.diagnosis of pulmonary complication by physician .\nthe criteria for postoperative pulmonary complications were reviewed from preoperative health status . in the current study ,\n2 participants in group i and 5 participants in group ii were excluded from study because of poor surgical outcomes . 1 participant from group\ni declined to continue further as part of the study because of low pain threshold .\ndata from 113 participants from group i and 111 participants from group ii were analyzed .\nmean age of participants in group i was 36.70 8.69 years ( median : 37 years , range : 38 years ) with male to female ratio of 49 : 64 , whereas in group ii mean age of participants was 37.01 8.43 years ( median : 38 years , range 33 years ) with male to female ratio of 38 : 73 .\nthere was no significant difference noted in mode of admission among these two groups ( p = 0.43 ) .\ndiagnosis of the patients and procedure performed in both groups were almost the same as shown in table 1 .\nsimilarly , there was no significant difference in the duration of surgery ( p = 0.51 ) and pain score ( p = 0.32 ) among both groups .\nmean duration of surgery for group i was 64.91 mins ( median : 65 mins , range : 75 mins ) , whereas for group ii it was 63.3 mins ( median : 60 mins , range : 80 mins ) .\nsimilarly , participants in group i reported mean pain score on 3.8 ( median : 5 , range : 3 ) on given visual analogue scale ( vas ) ; however , mean pain score for participants in group ii was 3.9 ( median : 4 , range 5 ) . on evaluating postoperative status of patients ,\nsignificant difference was observed in participants of both groups in terms of early mobilization to bed to chair and upright mobilization for more than 10 minutes ( p < 0.001 ) .\npatients in group i were mobilized earlier from bed to chair ( mean : 342.9 mins , median : 340 mins , and range : 105 mins ) in comparison to patients in group ii ( mean : 1511.1 mins , median : 1500 mins , and range : 680 mins ) .\nlikewise , patients in group i had earlier mobilization for more than 10 minutes ( mean : 360.7 mins , median : 360 mins , and range : 125 mins ) in contrast to patients in group ii ( mean : 1570.5 mins , median : 1570 mins , and range : 680 mins ) .\nparticipants in group i who were early mobilized had fewer pulmonary complications ( 7.1% ) compared to group ii who had 29.7% participants suffering from pulmonary complications .\nas shown in table 2 , whoever fulfilled any three of the scholes et al . \non exploring the impact of counseling and support from staff for physiotherapy from group i participants , the majority of them ( 68.14% ) reported that counseling was very effective in providing them with motivation for early mobilization , as shown in table 3 .\nthe primary aim of this study was to evaluate effect of preoperative counseling along with physiotherapy support on facilitating early mobilization among patients undergoing abdominal surgery .\nthe findings of current study revealed that early mobilization is not associated with type of abdominal surgery and its duration .\nlikewise , previous study has also indicated no significant difference in length of anesthesia and mobility .\npostoperative early mobilization in combination with physiotherapy serves as a prophylaxis to reduce postoperative pulmonary complications .\nit has also been reported that change of position from supine to fowlers increases minute ventilation significantly .\nsimilarly , findings of current study revealed that delayed mobilization increases the risk of postoperative pulmonary complications as indicated by presence of fever , abnormal breath sounds , and cough .\nthis finding supports that early mobilization can prevent postoperative complications associated with surgery . in line with findings of current study\n. moderate level of mobility also improves muscle strength and alleviates adverse effects of immobility .\nhence , optimal level of mobilization is desirable among surgical patients to prevent morbidity associated with inappropriate mobilization . in the current study ,\npatients who were mobilized earlier reported that preoperative counseling and support of physiotherapy staff were effective . in line with the current study findings\n, the literature revealed that increase in physical activity can be achieved among preoperative patients via continuous support .\npostoperative physical activity interventions have also proved to be effective in providing better surgical outcome [ 14 , 15 ] .\none of the study findings revealed that preoperative instructions about exercise impact postoperative compliance with exercise .\nsuch preoperative cognition interventions have proved to be effective in increasing postoperative physical activity . moreover , in developing countries where literacy level is low such interventions can significantly affect outcome of abdominal surgeries .\nthus , preoperative counseling and support of physiotherapy staff can improve compliance with early mobilization which is proved to be effective in reducing postoperative pulmonary complications .\nearly postoperative mobilization following abdominal surgery is proved to be effective in reducing pulmonary complications . in addition , preoperative counseling along with physiotherapy support can foster early mobilization among patients undergoing abdominal surgery .\nhence , counseling regarding early postoperative mobilization should be promoted among patients undergoing abdominal surgery to improve surgical outcome .", "answer": "background and objectives . \n preoperative counseling is effective to foster early postoperative mobilization that reduces pulmonary complications following abdominal surgery . \n this study aims at evaluating the effect of preoperative counseling regarding postoperative mobilization and its impact on reducing pulmonary complications . \n design and setting . \n randomized control trial was conducted at the department of surgery of a tertiary care hospital , karachi . \n patients and materials . patients who underwent abdominal surgery and \n met inclusion criteria were recruited . \n all participants were randomly divided into two groups . \n both groups received information about the surgery and group i received additional counseling for postoperative mobilization . \n all patients were encouraged for postoperative mobilization . \n scholes et al . \n criteria were used to evaluate postoperative pulmonary complications . \n results . in total 232 participants were recruited and divided into two groups . \n there was no significant difference in participants ' age ( p = 0.79 ) , duration of surgery ( p = 0.5 ) , and pain score ( p = 0.1 ) of both groups . \n however , significant difference was identified in mobilization from bed to chair and mobilization for > 10 minutes . \n patients in group i experienced less pulmonary complications in comparison with group ii .", "id": 94} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit provides an impervious seal , fills the irregularities and minor discrepancies between the root canal wall and core filling material , and assists in microbial control if microorganisms were left on the root canal walls or in the tubules.[15 ] ideally , a thin layer of the sealer should be evenly applied to canal walls prior to the placement of the core filling material .\nthe thickness of the endodontic sealer layer is very influential in the quality of the root canal filling.[612 ] an inadequate sealer coating may result in voids and permit bacterial microleakage which leads to endodontic failure . on\nthe other hand , excess placement of the sealer can result in its extrusion beyond the apical foramen which can prevent or delay healing .\nmoreover , most sealers dissolve over time and the dissolution is probably responsible for the increase in leakage along the root fillings over time.[1720 ] therefore , the amount of sealer should be kept to a minimum and should only be found in a thin layer between the gutta - percha and the wall of the canal .\nseveral techniques of sealer placement have been described in the literature , such as the use of a file , lentulo spiral , absorbent paper point , gutta - percha cone , and an ultrasonic file .\neach technique may produce different distribution of the sealer onto the canal walls , which may affect the sealing . at present\n, there is no evidence to suggest that one method is better and reliable than others .\nhence , the purpose of this study was to evaluate the influence of three most commonly used methods of sealer placement on the sealing ability of the sealer .\none hundred and nineteen ( 119 ) human permanent central incisors teeth that had no caries , restorations , or any other noticeable defects were collected , stored in 0.9% isotonic saline , and used in this in vitro study .\nthe crowns of the teeth were removed at the cementoenamel junction by using a hard tissue cutter ( exact , germany ) under water cooling .\nthe working length was determined by introducing a size 10 k file into the canal until it could be seen at the apical foramen .\nthis length was measured and the working length was set 1 mm short of the resultant measurement .\nall the teeth were instrumented to a size f3 protaper ( dentsply maillefer , switzerland ) following the full sequence recommended by the manufacturer . during preparation and between each protaper file ,\nthe canals were irrigated with 2 ml of 5.25% naocl by using a disposable syringe and a 25-gauge needle .\nalso a size 10 hand file was introduced to remove any debris and to ensure the patency of the apical foramen .\nall root canals were then irrigated with 5 ml of 17% ethylene diamine tetra acetic acid ( edta ) followed by 5 ml of 5.25% naocl .\nfinally , the root canals were flushed with distilled water and dried with absorbent paper points .\nthe instrumented teeth were divided randomly into 3 experimental groups of 33 teeth each in addition to 2 groups which served as positive and negative control groups of 10 teeth each [ table 1 ] .\ngroups , number of specimens , and sealer placement techniques root canal obturation was performed by using the cold lateral condensation technique .\nafter sealer application according to the groups as shown in table 1 , the prefitted size 30 master gutta - percha cone was placed .\nthe process was repeated until the spreader penetrated only into the coronal one - third of the root canal space .\nexcess gutta - percha was removed with a heated instrument and the remainder was condensed vertically with a cold plugger .\nthe teeth were stored in 100% humidity at 37c for 7 days to allow the sealer to set completely .\nafter 7 days the external root surfaces were coated by two layers of nail polish except the coronal orifices . in the positive control group ,\nno sealer was used and the nail polish was applied as the experimental group . while in the negative control group , the instrumented canals were filled with the sealer using rotary lentulo spiral and cold lateral compaction .\nthen , the external root surfaces were entirely coated with two layers of nail polish , including the coronal orifices . each tooth was subsequently immersed in an aqueous solution of 2% methylene blue dye with ph 7.0 in an individual container and kept in the incubator at 37c for 3 days .\nthe specimens were then decalcified in 5% nitric acid for 72 h and dehydrated gradually in ascending concentrations of alcohol to 100% .\nmethyl salicylate was used overnight to clear the teeth . for linear dye penetration assessment ,\neach tooth was sectioned longitudinally by using a hard tissue cutter ( exakt , japan ) .\nmeasurements were done by a blinded assessor under a light microscope ( leica , germany ) at x20 magnification .\nthe coronal leakage was measured to the nearest 0.01 mm , from the coronal end of gutta - percha , to the most apical extent of dye , taking into consideration the region of highest penetration .\nthis was completed using leica image analyzer software ( leica , germany ) , connected to the microscope .\nten teeth of each experimental group were randomly selected and dye penetration was measured again after 1 week by the same investigator to determine examiner reliability .\nthe data of the first and second measurements were tested using a single - measured intraclass correlation statistic ( icc ) .\nthe difference in the amount of linear dye penetration between groups was compared using anova .\nthe icc was 0.99 ( 95% ci : 0.991.00 ) suggestive of a high examiner reliability . due to technical problems during the experiment , one specimen was lost in group g1 , resulting in 32 samples for this group .\nthe positive controls demonstrated complete dye penetration throughout the length of the canal in all teeth .\nin contrast , the negative controls showed no evidence of leakage in any of the samples .\nmeans of linear dye penetration and standard deviations for all groups are summarized in table 2 .\nthere was no significant difference ( p = 0.305 ) of dye penetration among all groups .\none of the objectives of root canal treatment is to provide a hermetic seal of root canal space .\nthis seal is usually produced by using a semisolid or solid core material in a combination with the endodontic sealer .\na solid core can not produce the desired hermetic seal ; thus , the endodontic sealer is required to provide three - dimensional obturation .\nthe experimental system of this study was tested by using both positive and negative control groups .\nthe positive control specimens showed total dye penetration throughout the root canal , which indicated that it is absolutely necessary to use a sealer to fill voids and gaps between the core material and the root canal walls and further confirmed the fact that filling the root canal with only the core obturating material without a sealer resulted in an increased leakage .\nhowever , the negative control specimens demonstrated no dye penetration , which indicated that two coatings of nail polish were an effective means of preventing dye penetration .\nthe results of this study showed no statistically significant difference ( p = 0.305 ) in microleakage among the three different tested techniques of sealer placement .\nhowever , the rotary lentulo spiral group produced the highest value of microleakage and the master gutta - percha coating group had the smallest mean microleakage value .\nit was expected that the rotary lentulo spiral group will produce a better adaptation of the sealer onto the canal walls with even thickness which in turn leads to a better seal but the results of this study did not support our assumption .\nfirst , more amount of sealer was introduced into the canal as compared with other techniques , and as the sealer shrunk during setting , more gaps and voids might had been created that had contributed to the highest value of microleakage .\nsecond , a high volume of the sealer material may also interfere with the placement of additional accessory points which leads to less gutta - percha volume percentage compared to the amount of sealer .\nthird , the use of rotary lentulo spiral during sealer placement may force some air bubbles into the material that will lead to void formation and microleakage , whereas , the endodontic sealer coating of master gutta - percha cone produced less sealer thickness with less potential void formation compared to the other techniques that eventually might have contributed to the smallest microleakage value obtained by this group .\nour results are in accordance with wiemann et al . 's , who compared the influence of four methods , file , lentulo spiral , ultrasonic files , and master gutta - percha , of sealer placement on the sealer sealing ability .\nin addition , they reported that less sealer was present in the apical third compared to the coronal and middle thirds of the root canal .\nkahn et al . investigated the efficacy of six methods of sealer placement using clear plastic blocks with simulated curved canals .\nthey concluded that the lentulo spiral and the max - i - probe delivery system were the most effective means of sealer placement , followed by ultrasonic and sonic files , and the least effective methods were the paper point and the k file . in this study ,\nthe three methods of sealer placement showed comparable results and could be used in clinical practice .\nhowever , as the master gutta - percha coating technique had produced the lowest microleakage values , it would be suggested to be used for better results .\nthe master gutta - percha coating technique is the simplest method among the three methods tested and it requires no additional instruments and procedures .\nfurther research perhaps is needed to study the effect of different sealer placement methods with different obturation techniques .\nwithin its limitations , this study showed that the three tested techniques of sealer placement provided a comparable seal .\nhowever , the master gutta - percha coating technique could be preferable as it produced the least leakage value , and no extra instrumentation and procedures are needed in its application .", "answer": "aim : the aim of this in vitro study was to evaluate the sealing ability of an endodontic sealer following different techniques of its placement.materials and methods : a total of 119 permanent human anterior teeth were prepared by using manual protaper and randomly divided into three equal groups of 33 teeth each . \n the teeth were obturated with the cold lateral condensation technique and ah26 sealer which was placed by using the following : g1 : rotary lentulo spiral ; g2 : manual lentulo spiral ; and g3 : master gutta - percha coating . the remaining 20 teeth served as positive and negative controls . the samples were immersed in the methylene blue solution for 3 days and longitudinally sectioned for dye penetration assessment and analyzed using a stereomicroscope.results:there was no statistically significant difference ( p = 0.305 ) among the three groups . \n however , the rotary lentulo spiral technique and the master gutta - percha coating technique showed the highest ( 4.5 mm ) and the lowest ( 3.8 mm ) microleakage values , respectively.conclusion:different techniques of sealer placement used in this study provided a comparable seal . \n however , the master gutta - percha coating technique might be preferable because of its ease of use .", "id": 95} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na rare , potentially fatal and usually self - limiting adverse effect of therapy with enalapril , the angioedema , is always a challenging encounter for an intensive care specialist .\nthe unpredictability of clinical course and the risk of airway compromise with not so high end airway management gears at hand make it more challenging in a rural health setup .\nincidence of enalapril - induced angioedema is three times more common in population of african origin .\nbotswana provides universal health care to its citizens , and health sector is almost completely under government management .\nwe came across two cases in a very short window of about a month at a rural health center .\na 74-year - old female was admitted to the emergency department of sekghoma memorial hospital , serowe village , botswana , past midnight with progressive swelling of her face , tongue and breathing difficulty for about 8 h. the family gave a history of change of antihypertensive medication recently .\nshe has been started on tablet enalapril , 20 mg , once daily , orally , 2 days back . on examination , she was conscious , coherent but very anxious .\non auscultation of chest , air entry was good bilaterally and there were some conducted sounds from pharynx due to excessive secretions .\nthe tongue was grossly swollen , hard in consistency , it was wedged between the teeth and she was not able to close her mouth [ figure 1 ] .\nit was not possible to transfer this case to a tertiary care hospital by helicopter as there were landing issues in darkness .\nthe patient was started on oxygen support at the rate of 5 l / min by facemask for building up her oxygen reserves in case of airway emergency .\nlateral view x - ray of neck was done which showed airway patency as fine [ figure 3 ] .\nelective blind nasal intubation as a proactive airway management was risky due to less chances of success and more risk of further airway compromise .\nthere were no ear , nose , and throat ( ent ) specialists available for either evaluation or surgical airway management .\nshe was injected with 100 mg of hydrocortisone , intravenously and 0.5 ml of injection adrenaline ( 1:1000 ) subcutaneously .\nshe was observed for about 30 min in which she gradually became worse and swelling of face and tongue increased .\nwe decided to go ahead with fresh - frozen plasma infusion under intravenous beta - blocker antihypertensive coverage .\nher blood group was o - positive and hospital being a peripheral center ; we had only blood storage facility where o - positive fresh - frozen plasma was not available .\nwe decided to go ahead with transfusion of the only pint of o - negative fresh - frozen plasma available at our storage facility .\ninjection metoprolol , 5 mg , intravenously was instituted and then we started with o - negative fresh - frozen plasma infusion intravenously , 220 ml over next 30 min . on post - fresh - frozen plasma infusion ,\n, she recovered grossly and after 6 h she was able to close her mouth completely .\nthe patient on arrival to intensive care unit the patient after fresh - frozen plasma transfusion lateral x - ray of neck taken to decide the airway management\nace inhibitors are one from the most widely used antihypertensive worldwide , particularly for the diabetics to prevent nephropathy and in cases of left ventricular dysfunction or heart failure . soon after the development of ace inhibitors , wilkin et al . reported angioedema and proposed enhanced kinin effects from inhibition of kininase ii as the underlying mechanism .\nlater , reports of ace inhibitor - related angioedema estimated an incidence between 1/1000 and 3/1000 .\nangioedema was about three times more likely to occur among black patients ( 1.62% vs. 0.55% for white patients ) and slightly more likely in women ( 0.84% vs. 0.54% for men ) .\nthe incidence of angioedema was lower in diabetic patients ( 0.43% ) and higher in patients with renal disease ( 1.63% ) or a history of rash ( 2.48% ) .\nthe most common sites of angioedema were the lips ( 49% ) and the face ( 52% ) .\nswelling of the tongue , neck , or eyelids occurred in approximately 1 of 5 patients with angioedema .\nthe incidence of angioedema was not affected by prior or current use of ace inhibitors at randomization .\nthey identified black race , history of drug rash , age > 65 years , and seasonal allergies as independent risk factors for angioedema related to enalapril .\nslater et al . reported a 14-fold higher incidence of angioedema in the 1 week compared with later time intervals .\nhedner et al . reported that about half of the cases occurred in the 1 week of therapy .\n, these patients should be carefully examined for any evidence of respiratory compromise such as stridor , a markedly enlarged tongue , symptoms of dyspnea , acutely presenting dysphagia , and drooling of saliva .\nlateral view x - ray of neck may be an important tool to decide about intubation .\nthe decision of when to intubate should be made early based on standard physiologic criteria , recognizing that intubation may be difficult secondary to edema of the airway .\ncricothyrotomy or emergency tracheostomy is required for maintenance of the airway if oropharyngeal and nasopharyngeal intubation fails .\nfluid resuscitation and therapy with vasopressors may be required if the patient is hemodynamically unstable .\nhypotension can be seen in severe cases secondary to the extravasation of large amounts of fluid into the extravascular space .\npatients presenting with respiratory symptoms should immediately receive 0.5 ml epinephrine ( 1:1000 ) subcutaneously .\ntherapy with antihistamines and steroids should be started initially in all patients , as a true allergic reaction can not be excluded . although the role of epinephrine , antihistamines , and corticosteroids is controversial in nonmast cell - mediated angioedema , i.e. ace inhibitor - related angioedema , in our case , we used all the three above - mentioned agents but there was no clinical improvement .\nfresh - frozen plasma has been used successfully for the treatment of resistant , life - threatening angioedema induced by ace inhibitor .\nthe benefit of fresh - frozen plasma in this condition may be due to the effect of kininase ii in breaking down accumulated bradykinin . in this case , we used fresh - frozen plasma , and the clinical improvement was observed .\nwe recommend that in case of life - threatening enalapril - induced angioedema in rural setup , where advanced airway management procedures may be difficult , we must give an early thought about starting fresh - frozen plasma .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .", "answer": "angioedema , a rare , potentially fatal and usually self - limiting adverse effect of therapy with enalapril , is always a challenging encounter for an intensive care specialist in a rural setup . here \n , we present a 74-year - old female , who presented to the emergency department of sekgoma memorial hospital , serowe village , botswana , with progressive swelling of her face , tongue and breathing difficulty just 2 days after starting tablet enalapril . \n she failed to respond to usual treatment with adrenaline , steroids , and h1-antihistaminic agent , but she responded well with intravenous fresh - frozen plasma infusion . \n this helped us manage a difficult airway situation in a less equipped rural health center .", "id": 96} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndr clark is the director of the centre for gambling research at ubc , which is supported by funding from the province of british columbia and the british columbia lottery corporation ( bclc ) .\ndr clark has provided paid consultancy to cambridge cognition ltd . on issues relating to neurocognitive assessment .\ndr clark has not received any other direct or indirect payments from the gambling industry or any other groups substantially funded by gambling to conduct research or to speak at conferences or events .", "answer": "billieux et al . ( 2015 ) propose that the recent proliferation of behavioral addictions has been driven by deficiencies in the underlying research strategy . \n this commentary considers how pathological gambling ( now termed gambling disorder ) traversed these challenges to become the first recognized behavioral addiction in the dsm-5 . \n ironically , many similar issues continue to exist in research on gambling disorder , including question - marks over the validity of tolerance , heterogeneity in gambling motives , and the under - specification of neuroimaging biomarkers . \n nevertheless , i contend that the case for gambling disorder as a behavioral addiction has been bolstered by the existence of clear and consistent functional impairment ( primarily in the form of debt ) , coupled with the development of a public health approach that has given emphasis to product features ( i.e. the structural characteristics of gambling forms ) as much as individual dispositions ( the addictive personality ) .", "id": 97} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmost pituitary adenomas are clinically inactive . in patients with long - standing compression of the optic chiasm , ganglion cells may undergo axonal degeneration .\nspectral domain optical coherence tomography ( sd - oct ) is able to identify retinal nerve fiber layer ( rnfl ) and ganglion cell loss in the retina .\nwe present a case in which sd - oct was used to diagnose an asymptomatic pituitary macroadenoma .\nsd - oct identified atrophy of the ganglion cell and nerve layers , with preservation of outer layers bilaterally .\nas macroadenomas enlarge , they can induce uncrossed axon loss , resulting in nasal field defects and reduced visual acuity . in these cases , there is atrophy of the nasal and temporal portions of the optic disc , thus occupying a horizontal band across the disc .\nsd - oct is able to identify rnfl loss in eyes with band atrophy of the optic nerve , which correlates with visual field defects found in perimetry .\nsd - oct is a useful tool to assess the structural and functional damage of ganglion cells . in our case\nthe sd - oct demonstrated a symmetrical loss of the rnfl and the ganglion cell layer in both eyes , indicating important optic nerve damage .\npituitary adenoma is the most common cause of the chiasmal syndrome.1 the tumor is classified based on size as microadenoma , smaller than 10 mm , or as macroadenoma when it exceeds 10 mm in diameter.2 some tumors secrete one or more hormones in excess , so - called secretory pituitary adenomas , but most are clinically inactive.3 classically , the nonsecretory tumors present with vision loss,4 whereas patients with secretory tumors are usually referred to ophthalmologists for evaluation due to hormonal imbalances that affect bodily functions.5 in patients with long - standing compression of the optic chiasm , ganglion cells may undergo axonal degeneration4 .\noptical coherence tomography ( oct ) is able to identify retinal nerve fiber layer ( rnfl ) and ganglion cell loss in retina.6,7 we present a case in which the oct ( 3d oct-2000 spectral domain oct , topcon corporation , tokyo , japan ) was used to diagnose an asymptomatic pituitary macroadenoma .\nthe authors adhere to the international standards developed in the 2 conference on research integrity in singapore ( 2010 ) , while performing this study .\nthe patient agreed to have their case published , and all information presented is non - identifiable.8\na 48-year - old , caucasian female presented with progressive vision loss in both eyes for several months .\nher past ocular , medical , and family history was non - contributory with no fatigue , loss of libido , no mood change , and no weight change . on examination , best - corrected visual acuity was hand motion in the right eye and 2/3 in the left eye .\nspectral domain optical coherence tomography ( sd - oct ) demonstrated diffuse atrophy of the ganglion cell and nerve layers , with preservation of outer layers bilaterally ( figure 1 and figure 2 ) .\nmagnetic resonance imaging of the brain was performed and a pituitary macroadenoma with suprasellar extension was observed ( figure 3 ) .\npituitary adenomas are common benign tumors of the pituitary gland that account for 12% of all intracranial tumors.9 people can develop pituitary adenomas at any age .\nsome adenomas secrete hormones in excess . of the secretory tumors , the most common are prolactinomas.5 they may be relatively small when detected .\nthe most common symptoms include headaches , menstrual changes in females , sexual dysfunction in males , vision problems , and behavioral changes.5 diagnostic imaging may include a high - resolution , t1 weighted , gadolinium enhanced magnetic resonance imaging.10 other secretory tumors may secrete corticotropin , growth hormone , gonadotropins , or thyroid - stimulating hormone.11 adenomas remain confined to the pituitary gland , but when a pituitary adenoma is 10 mm it is called a macroadenoma .\nmacroadenomas can compress the rest of the pituitary gland and surrounding structures , such as the crossing retinal ganglion cell axons in the optic chiasm , resulting in bitemporal visual field loss.4 as the tumor enlarges , it has been shown to induce uncrossed axons loss , resulting in nasal field defects and reduced visual acuity . in these cases , there is atrophy of the nasal and temporal portions of the optic disc with relative sparing of the superior and inferior parts where the majority of temporal fibers enter .\nthe optic atrophy occupies a horizontal band across the disc , called bowtie or band atrophy.12,13 oct is a noninvasive technique that allows cross - sectional imaging of the retina and quantifies the thickness of the rnfl around the optic nerve head .\na number of studies have demonstrated that oct is able to identify rnfl loss in eyes with band atrophy of the optic nerve.6,7 the degree of rnfl thickness reduction has been shown to correlate with that of visual field defects using goldmann perimetry4 and automated static perimetry.14,15 this fact gives oct prognostic value regarding the visual outcome , as demonstrated in different studies.16,17 oct is a useful tool to assess the structural and functional damage of ganglion cells , objectively and quantitatively.4 in our case the sd - oct demonstrates a symmetrical loss of the rnfl and the ganglion cell layer in both eyes , indicating important optic nerve damage .\nsd - oct can help in the diagnosis of adenomas in equivocal situations in which there is only subtle optic nerve pallor in the setting of nonspecific visual complaints or visual field defects , or when patients are referred to screen for subclinical compressive optic neuropathies .", "answer": "introductionmost pituitary adenomas are clinically inactive . in patients with long - standing compression of the optic chiasm \n , ganglion cells may undergo axonal degeneration . \n spectral domain optical coherence tomography ( sd - oct ) is able to identify retinal nerve fiber layer ( rnfl ) and ganglion cell loss in the retina . \n we present a case in which sd - oct was used to diagnose an asymptomatic pituitary macroadenoma.clinical casea 48-year - old female presented with progressive vision loss in both eyes . \n sd - oct identified atrophy of the ganglion cell and nerve layers , with preservation of outer layers bilaterally . \n magnetic resonance imaging of the brain showed a pituitary macroadenoma . \n the pathological diagnosis was nonfunctioning adenoma.discussionas macroadenomas enlarge , they can induce uncrossed axon loss , resulting in nasal field defects and reduced visual acuity . in these cases , there is atrophy of the nasal and temporal portions of the optic disc , thus occupying a horizontal band across the disc . \n sd - oct is able to identify rnfl loss in eyes with band atrophy of the optic nerve , which correlates with visual field defects found in perimetry . \n sd - oct is a useful tool to assess the structural and functional damage of ganglion cells . in our case \n the sd - oct demonstrated a symmetrical loss of the rnfl and the ganglion cell layer in both eyes , indicating important optic nerve damage .", "id": 98} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncerebral palsy ( cp ) is a non - progressive neurodevelopmental disorder that includes a wide \n spectrum of syndromes related to the early onset of posture and motor impairment1 .\ndysfunctional postural control and movement \n patterns lead to limitations in participation in activities of daily living ( adl)2 .\naccording to jeong et al.3 cp is the most common infant brain injuries \n in south korea , representing 57.8% of brain injuries in the 09 years category .\nmanagement \n of children with cp requires various rehabilitative approaches that draw on the expertise of \n many specialists in different disciplines .\nsome of the current clinical therapeutic \n interventions include traditional physical and occupational therapy , neurodevelopmental \n treatment , the vojta method , and sensory integration to improve postural control , balance , \n and locomotion for improved participation in adl4 .\nmany children with cp not only exhibit neuromotor deficits but demonstrate difficulties \n with sensory processing and praxis5 . \n\nsensory integration is a dynamic process that synthesizes , organizes and processes incoming \n sensory information from the body and the environment in order to create purposeful and \n goal - directed responses6 .\ngood sensory \n integration leads to the development of good body scheme , self - image , integration of \n primitive reflexes , balance , postural stability , ability to motor plan , coordination of two \n sides of the body , and eye - hand coordination7 . among the sensory systems ,\nalthough it may be important to apply sensory integration treatment \n techniques and sensory based activities for children with cerebral palsy , therapists maybe \n reluctant to do so as the evaluation of vestibular processing can prove to be difficult9 and vestibular activities may increase \n muscle tone in unwanted areas5 .\nthe \n purpose of this case report is to present the effects of vestibular stimulation on a child \n with hypotonic cerebral palsy through the use of swings .\nthis case was referred to this author via the child s occupational therapist who felt the \n child would benefit from this study .\ninje university affiliated hospital ethics review board \n approved this case study and informed consent was obtained from the child s mother .\nthe subject was a 19-month - old boy with a diagnosis of hypotonic cerebral palsy ( cp ) and \n oscillating nystagmus .\nhe was born at 39 weeks of gestation via caesarian section and there were no \n complications reported at birth .\nhowever his mother reported him to be a fussy baby who \n cried often and appeared to be colicky .\nhe started to demonstrate head \n control at about 8 months and ability to maintain the ring - sitting position for less than 30 \n seconds using his hands to prop himself up when put in a seated position ; however he had not \n made any further progress in gross motor skills since . at 5 months of age\n, he started to \n receive therapy for developmental delays , including hospital based occupational therapy 2 \n times per week , physical therapy using the neurodevelopmental treatment ( ndt ) technique and \n the vojta method 2 times per week , and sensory stimulation once a week .\nhe was reported to \n cry incessantly and was inconsolable in all of his therapy sessions from when he started \n therapies at 5 months to his initial assessment for this case study .\npre and post - intervention tests were completed by the researcher using the bayley scales of \n infant and toddler development ii .\nafter the pre - intervention test and during the \n intervention phase all of the subject s other therapies were stopped to control the effect \n of vestibular stimulation without other interventions .\nthe subject was provided with \n vestibular stimulation 3 times per week for 10 weeks in 1 hour sessions conducted by his \n mother as instructed by the researcher .\neach session started with 30 minutes of swinging on \n an infant swing for all 10 weeks .\nthe vestibular stimulation protocol using different swings \n is shown in table 1 \n table 1.vestibular stimulation protocol \n .\nthe subject s mental raw score was 21 with a corresponding developmental age of 1 month , \n and his motor raw score was 40 with a corresponding developmental age of 6 months , \n pre - intervention .\nthe subject s mental score increased to 46 with a corresponding \n developmental age of 4 months , and his motor score increased to 58 with a corresponding \n developmental age of 10 months ( tables 2table 2.results of bayleyscalepre - testpost - testraw scorepercentile % raw scorepercentile % mental 2146motor4058behavior ratingorientation e111%3223%emotional r121%286%motor q151%251%additional i14total r score391%897% , 3table 3.results of bayley , developmental agepre - testpost - testmental developmental age1 month4 monthsmotor developmental age6 months10 months ) .\nthe results show that the subject exhibited improved mental and motor skills of 3 and 4 \n months respectively which is a significant improvement at this age of development .\nthe \n subject was able to ring - sit for less than 30 seconds at pre - test , and was not able to \n transition from supine or prone to sitting or from sit to pull to stand .\nhowever after 10 \n weeks of intervention he was able to walk with his hand held and independently for about 15 \n meters before losing balance , and he was able to transition from supine or prone to sit to \n pull to stand independently .\nas for mental skills , the subject showed no interest in toys or \n people and he cried throughout the entire therapy session at the beginning of this study ; \n however once he was introduced to vestibular stimulation by swinging , he smiled , laughed and \n started to interact with both toys and people .\npostural control is dependent on the integration of proprioception , vision and vestibular \n systems of which vestibular input is particularly important10 .\nadequate motor performance and postural control is needed for an \n infant or a young child to independently perform and participate in play , activities of \n daily living and social interactions .\ninfants diagnosed with cerebral palsy demonstrate \n difficulties with postural control and locomotion and can miss opportunities to explore \n their environment11 .\nthe subject in this \n case study was diagnosed with hypotonic cerebral palsy and demonstrated poor postural \n control , only being able to maintain a ring - sit position using his hands to prop himself up \n for 30 seconds .\nthe subject was not able to explore his environment due to lack of mobility \n and he did not use his hands at the beginning of this research .\none possible explanation for \n his incessant crying during all of his therapy sessions in the past year is that he had an \n inefficient vestibular system .\nsensory integration of the vestibular system provides a \n gravitational security which helps with the emotional well - being5 however , due to the subject s poor integration of the \n vestibular system , he may have been fearful of being moved during all of his therapies which \n made him resistant and cry .\nwhen the subject was presented with intense vestibular inputs on \n different swings , he stopped crying very quickly and responded by holding his head and trunk \n more erect and eventually improved his postural control enough for him to walk . at the \n beginning of this study ,\nthe subject made no attempt to move his body and spent most of his \n waking hours lying in supine .\nwhen his mother put him in sitting position or moved him , he \n cried and was resistant to being moved .\nhowever by the end of this research the subject \n demonstrated improvements in movement in space and transitioning from supine or prone to \n sitting and from sitting to pull to stand independently .\nthe vestibular system is thought to be a primary organizer of sensory information and \n contributes to physical and emotional security12 .\nthis case study shows that improving the integration of the \n vestibular system through the use of swings resulted in the improvement of the subject s \n postural control , movement , exploration , and emotional well - being .\nthe subject s mother \n reported feeling anxious and helpless as she did not know how to console or interact with \n her crying child .\nhowever once the subject had been introduced to vestibular inputs on \n different swings , he responded almost immediately by not crying , and started to laugh out \n aloud and babbling .\nboth the subject and his mother appeared much more relaxed with each \n other and able to interact with each other better as the subject decreased crying and \n started to explore his environment .\nthe subject s mother reported that at the beginning of \n this study she could not take him anywhere to play as he cried the entire time when she took \n him to playgroups and playgrounds but from about the middle of the intervention of this \n study , he started to feel comfortable when taken to new environments .\nthe level of subject s \n comfort , exploration , interaction , and play had improved significantly by the end of this \n study .\nthis study has demonstrated that vestibular inputs through the use of swings has improved \n the subject s postural control , movement in space , emotional well - being , interaction with \n people and environment and participation in play .\ntherefore therapists may wish to consider \n providing vestibular inputs for children with hypotonic cerebral palsy in treatments to \n facilitate postural control and emotional well - being .\nsensory based activities must be \n provided by a well trained and experienced therapist as children with cerebral palsy present \n neuromotor deficits as well as sensory issues .\na limitation of this case study is that there \n was only one subject which makes it difficult to generalize the findings to a wider \n population .\ntherefore , further research with larger sample sizes are needed to determine the \n effectiveness of vestibular inputs through the use of swings on children with hypotonic \n cerebral palsy .\nfuture studies should also look at the effectiveness of sensory integration \n and ndt in the treatment of children with cerebral palsy .", "answer": "[ purpose ] the purpose of this case report is to present the effects of vestibular \n stimulation on a child with hypotonic cerebral palsy through the use of swings . \n [ case \n description ] the subject was a 19-month - old boy with a diagnosis of hypotonic cerebral \n palsy ( cp ) and oscillating nystagmus . \n the subject had received both physical therapy and \n occupational therapy two times per week since he was 5 months old but showed little to no \n improvement . \n [ methods ] pre and post - intervention tests were completed by the researcher \n using the bayley scales of infant and toddler development ii . the subject was provided \n with vestibular stimulation 3 times per week for 10 weeks in 1 hour sessions conducted by \n his mother as instructed by the researcher . during this research \n all other therapies were \n stopped to determine the effects of the vestibular stimulation and to exclude the effects \n of other therapies . \n [ results ] the subject demonstrated improvement of 4 months in motor \n skills and of 3 months in mental skills as shown by the bayley scales of infant and \n toddler development ii . [ conclusion ] vestibular stimulation was effective in improving \n postural control , movement , emotional well - being , and social participation of a child with \n hypotonic cerebral palsy .", "id": 99} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndata on all campylobacter isolates obtained from fecal or lower gastrointestinal tract samples , reported in england and wales from 1990 through 2007 , were extracted from the national laboratory database ( labbase ) and stored in a microsoft access ( microsoft corp . ,\ncases were assigned to 10-year age groups and to geographic areas on the basis of laboratory location ( northern , mid - country , southern ) .\nthe season was assigned on the basis of the earliest available specimen date ( spring , march may ; summer , june august ; autumn , september \ndata on cases of cryptosporidiosis and nontyphoidal salmonellosis for the same period were extracted , grouped , and categorized and manipulated as above for comparative purposes .\ndenominator data for england and wales for the same period were obtained from the office for national statistics .\ndata were analyzed in microsoft excel 2003 and stata version 10 ( statacorp , college station , tx , usa ) .\nestimates of incidence per 100,000 population were calculated throughout ; relative risks ( rr ) and 95% confidence intervals ( cis ) were calculated as required . from 1990 through 2007 in england and wales , 838,436 cases of campylobacter infection were reported ; patient age was available for 810,632 case - patients ( 96.7% ) . from 1990 through 1999 , incidence increased in all age groups ( figure 1 ) , but the increase was proportionate to increasing age ( 09 years of age rr 1.07 [ 95% ci 1.031.10 ] ; 1019 years rr 1.47 [ 95% ci 1.411.55 ] ; 2059 years rr 1.78 [ 95% ci 1.751.81 ] ; > 60 years rr 2.51 [ 95% ci 2.412.61 ] ) . from 2000 through 2004 , incidence declined in all age groups .\nhowever , although the degree of decline was similar for those 09 years of age ( rr 0.77 [ 95% ci 0.740.8 ] ) , 1019 years ( rr 0.73 [ 95% ci 0.700.76 ] ) , and 2059 years ( rr 0.75 [ 95% ci 0.740.76 ] ) , for patients > 60 years of age , the degree of decline was significantly lower ( rr 0.88 [ 95% ci 0.860.91 ] ; p<0.001 ) .\nfinally , although the incidence increased only moderately among those 1019 years of age ( rr 1.02 [ 95% ci 0.981.07 ] ) and 2059 years ( rr 1.04 [ 95% ci 1.031.06 ] ) from 2005 through 2007 , greater increases were observed for those 09 years ( rr 1.12 [ 95% ci 1.081.17 ] ) and those > 60 years ( rr 1.33 [ 95% ci 1.291.36 ] ) . during the surveillance period , therefore , the incidence among patients > 60 years of age , compared with the incidence among younger patients , increased markedly ( rr 0.45 [ 95% ci 0.440.47 ] in 1990 to rr 1.17 [ 95% ci 1.151.19 ] in 2007 ) .\nthis effect was observed for campylobacteriosis in both sexes , in 3 geographic areas of england and wales , and in all 4 seasons , but was not observed for nontyphoidal salmonellosis or cryptosporidiosis ( figure 2 ; technical appendix ) .\nincidence of laboratory - reported campylobacteriosis , england and wales , by age group , 19902007 .\nrelative incidence of campylobacteriosis by sex , region , and season , compared with rates of salmonellosis and cryptosporidiosis , among patients > 60 years of age , england and wales , 19912007 .\nnorthern , northwest , northeast , as well as yorkshire and the humber regions ; mid - country , wales , west midlands , east midlands , and east of england regions ; southern , london as well as southeast and southwest regions .\nsalmonellosis includes nontyphoidal salmonellae , with age data available for 356,270 of 380,915 case - patients ( 94% ) ; cryptosporidiosis includes age data for 76,462 of 79,808 case - patients ( 96% ) .\nwe report a striking change in the population at risk for campylobacteriosis in england and wales , which is independent of gender , geography , or season .\nthe absence of a similar change in the age distribution of laboratory - reported salmonellosis or cryptosporidiosis from the same population suggests that this is unlikely to be a surveillance artifact .\ncampylobacter infections are rarely typed beyond the genus level in england and wales , so infections are routinely reported as campylobacter species .\ntherefore , changes in the incidence of the various species that constitute this broad case definition could possibly explain some of the altered disease pattern reported .\nfor example , infections caused by certain species ( e.g. , c. fetus ) are more often associated with coexisting conditions that might occur more frequently in the elderly .\nfirst , isolation methods used in england and wales favor the growth of c. jejuni and c. coli ( 4,5 ) over that of other species , including c. fetus . furthermore , c. fetus normally causes systemic infections detected through blood culture , and the proportion of blood to fecal isolations of campylobacter species in patients > 60 years of age reported in england and wales remained constant from 1990 through 1999 ( 275/58,139 fecal isolations ; 0.47% ) , from 2000 through 2004 ( 185/44,349 ; 0.42% ) , and from 2005 through 2007 ( 135/31,637 ; 0.42% ) ( health protection agency , unpub . data ) . when disease incidence was ranked according to specific population group , children 09 years of age had the highest ranking in 1990 , but by 2007 , incidence for this age group ranked seventh of 9 age groups .\nthis finding led to the hypothesis that the introduction and increased utilization of the national health service s nhs direct ( a 24-hour telephone , online , and interactive digital tv service , which provided health advice and information ) at this time had a triage effect on those seeking care for children in this age group .\nthe 2 events are correlated in time ( initial nhs direct pilot sites began taking calls in march 1998 ; by april 1999 , 40% of the population of england had access , and by november 2000 , the service was available throughout england and wales ) , nhs direct has had a demonstrable negative effect on the use of general practice ( 7 ) , and infants and young children are overrepresented among calls to nhs direct about gastrointestinal conditions ( 8) .\nthe second infectious intestinal disease study in england , currently under way ( 9 ) , will provide further information upon which to assess this hypothesis , which is not readily testable by using laboratory data . by far the most striking\nfinding of this study is the emergence of older persons as the population most at risk for campylobacteriosis in england and wales .\nalthough the elderly were not the only group at risk in 2007 ( because of increasing incidence ) , the overall trend singles them out as the main emerging at - risk group ( the increase in other age groups requires continued monitoring , however ) .\nthe pattern of infection in older patients is perhaps predictable , given the similar pattern for incidence of listeriosis in england and wales since 2001 ( 10 ) . as life expectancy increases in the united kingdom ,\nthe number of persons living with chronic conditions is likely to increase ; these factors suggest that the incidence of campylobacteriosis in older persons will continue to increase in the future .\ntherefore , risk factors for campylobacter infection specific to older uk residents must be identified .\nrelative incidence of campylobacter infection in each year compared with that in 1990 among patients > 60 years of age infected with selected gastrointestinal pathogens , england and wales , 1991 - 2007", "answer": "to explore hypotheses for age - related changes in the incidence of campylobacter infections in england and wales during 19902007 , we analyzed electronic laboratory data . \n disease incidence was reduced among children , and the greatest increase in risk was for those > 60 years of age . \n risk factors for campylobacteriosis in the elderly population should be identified .", "id": 100} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbenign acute childhood myositis ( bacm ) is a self - limiting process characterized by sudden onset of muscle pain , more often calf pain , manifested by walking difficulty . since many clinicians are not familiar with bacm , it is often misdiagnosed and interpreted as a more severe and complex disease .\nwe report the case of a patient suffering from bacm in absence of any previous documented viral infections .\nwe underline how medical history and clinical examination are sufficient for a correct diagnosis of bacm , as well as to avoid unnecessary tests . based on the previous reports\n, we updated etiology and clinical data of bacm , and we propose differential diagnosis of muscle pain in children .\na 7-year - old boy with acute calf pain and progressive walking difficulty was referred to our pediatric center to rule out muscle degenerative diseases .\ntwo days earlier the child had suffered from fever , cough , malaise and rhinorrhea , which promptly resolved .\nthe onset of calf pain was early in the morning , and it was so sharp that he had to walk on his heels mimicking a spastic gait .\nthe child had undergone all compulsory vaccinations , and his previous clinical history was not suggestive of any remarkable diseases .\nno travels , trauma , vigorous exercise or similar episodes of limb pain were reported before onset of symptoms . on admission ,\nreflexes and sensitivity of the upper and lower limbs were also normal . at rest , the patient kept his feet in slight plantar flexion .\ngastrocnemius - soleus muscles on both sides were soft on palpation , and there were no inflammatory changes .\npassive dorsiflexion of the ankles caused sharp pain as well as passive stretching and gentle palpation of his calves . despite normal neurological examination ,\nthe patient was hospitalized in order to allow medical observation and exclude severe diseases . on admission laboratory tests\nshowed a significant increase in blood levels of creatinine phosphokinase ( 2161 u / l , normal range < 227\nu / l ) , alanine transaminase ( 69 u / l , normal range : 0 - 45 ) and aspartate transaminase ( 92 u / l , normal range : 17 - 59 ) .\nmg / l ) and white blood cell count ( 7400/l ) were within normal limits .\ncomplete blood count , electrolytes , blood urea nitrogen , creatinine , prothrombin time , partial thromboplastin time and other routine blood parameters were also within normal limits .\nfurthermore , serological tests ruled out recent viral infections by adenovirus , respiratory syncytial virus , cytomegalovirus , herpes virus and epstein barr virus , as well as serological tests for mycoplasma pneumonia .\nsince the patient refused to eat and drink , he received intravenous hydration for 24 h. during the 2 day of hospitalization pain spontaneously resolved and a normal gait was regained . considering\nthat daily urine output was normal , the boy was discharged , and no long - term follow - up was required .\nbenign acute childhood myositis is a self - limiting process which frequently affects the gastrocnemius and soleus muscles . in a review of 2004\nother agents such as enterovirus , mycoplasma pneumonia and dengue virus have been involved in the process . furthermore , five cases of bacm following h1n1 influenza a virus infection and human parainfluenza virus type 1 infection have been reported . in most cases ,\nthe disease is self - limiting and when the myositis develops the patient is already in the early convalescent phase of the viral illness .\nnevertheless , it is reported that 10/316 children ( 3% ) developed severe rhabdomyolysis , and temporary dialysis was necessary in six cases . during winter 20072008 , influenza b virus was responsible for a large number of cases of bacm in germany , especially among male children aged from 6 to 9 years .\nmedian time between the onset of fever and the beginning of bacm symptoms was 3 days . despite the clinical course of bacm being well described , mall et al .\nfurthermore , the exact current incidence , prevalence and pathogenesis of bacm are not known .\nthis could simply be explained by the increased tropism of viruses for immature muscle cells .\nfurthermore , each virus could act as a trigger in genetically predisposed children and in few patients with undiagnosed metabolic diseases .\nnevertheless , the onset may be mistaken for very severe neurological illness such as guillain barr syndrome or chronic autoimmune diseases . as a consequence unnecessary invasive tests , such as radiography , echocardiography ,\ndaily medical examination and urine dipstick ( with measurement of myoglobin ) are sufficient to promptly detect complications and rule out more severe illnesses and creatine kinase ( ck ) should be measured only at diagnosis in order to early exclude degenerative diseases .\nviral tests for bacm - related viruses should not be routinely performed because of the time interval between infection and seroconversion . moreover ,\nnot always etiological agents can be found , and antiviral drugs are not usually recommended . nevertheless , influenza test may be useful since influenza viruses can affect the severity of bacm .\nhowever , parents should be encouraged to monitor the child 's urine output and the appearance of coca - cola colored urine and swollen legs .\nhospitalization should be scheduled only when the patient 's parents do not seem able to monitor the condition of their child at home .\nwe report signs and symptoms which can help clinicians to make a correct differential diagnosis when a child suffers from acute muscle pain in table 1 .\n. a family history of neuromuscular disorders , myoglobinuria , trauma , chronic progression , rash , edema , muscle weakness or neurological diseases are not typically associated to bacm ; in these cases further investigation is required .", "answer": "acute muscle pain and walking difficulty are symptoms compatible with both benign and severe degenerative diseases . as a consequence , in some cases \n invasive tests and hospitalizations are improperly scheduled . \n we report the case of a 7-year - old child suffering from acute calf pain and abnormal gait following flu - like symptoms \n . a review of the literature will be helpful to better define differential diagnosis in cases of muscle pain in children . \n daily physical examination and urine dipstick are sufficient to confirm the diagnosis of benign acute childhood myositis ( bacm ) during the acute phase , to promptly detect severe complications and to rule out degenerative diseases \n . children with bacm do not require hospitalization , medical interventions or long - term follow - up .", "id": 101} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nposttraumatic cerebral edema leading to refractory intracranial hypertension is the main prognostic factor in brain - injured patients .\nmorbidity and mortality occur as a result of transtentorial herniation caused by mass effect due to cerebral swelling .\nthe combined medical and surgical objective during the acute phase is to prevent raised intracranial pressure ( icp ) and maintain cerebral perfusion pressure in order to limit the development of secondary lesions .\nearly decompressive craniotomy ( dc ) is a method for decreasing raised icp and has been associated with better outcomes . in neonates ,\nas the cranial sutures are open , any associated fracture may relieve the raised icp due to craniotomy flap - elevation like effect .\nan 8-day - old male child was brought to the emergency room with a history of fall from a cradle of about 3 feet height followed by loss of consciousness for half an hour .\nthere was no history of convulsions , vomiting or ear , nose , and throat bleed . on examination ,\nthe neonate was vitally stable , alert , conscious , moving all four limbs with no focal neurological deficit .\nthe physical examination showed a large swelling in the left temporal region behind the ear ( battle 's sign ) [ figure 1 ] .\nphotograph on the day of admission showing a swelling in the left temporoparietal region with battle 's sign computed tomography ( ct ) of the brain showed a large left sided frontoparietal contusion with brain herniation through the fracture segment [ figure 2 ] .\nplain axial computed tomography scan brain shows a large hyperdense area in the left frontoparietal region suggestive of a contusion ( black arrow ) , as well as brain herniation , with underlying sutural widening based on the clinical examination and ct findings , a decision was taken to medically manage the patient with anti - epileptic medications and monitor for any signs of raised icp .\nthe child showed progressive improvement in the neurological condition and was discharged after 8 days and asked to follow - up for dural repair and cranioplasty after 3 weeks .\nthe child was lost to follow - up and presented 2 months later with a cystic , nonpulsatile 5 cm 4 cm swelling in the left temporal region .\nct scan showed a large cystic lesion in the left temporoparietal region with underlying bone defect [ figure 3 ] .\na diagnosis of growing fracture skull ( posttraumatic leptomeningeal cyst ) was established , and surgical intervention planned .\nthe neonate underwent duraplasty with pericranial graft and cranioplasty with titanium mesh plate 70 days after the head injury insult [ figure 4 ] .\nthe infant tolerated the procedure well and was discharged after suture removal . on 6 months\nfollow - up , the infant was doing well with no neurological deficits or wound - related complications .\nplain axial computed tomography scan showing a large 6 cm 3.2 cm 5.3 cm cystic lesion in the left temporoparietal region with underlying bone defect in the temporal bone ( black arrow ) intraoperative photograph showing titanium mesh plate with underlying pericranial dural graft\nhead injury is likely to occur in children and adolescents ranging from 0 to 19 years in approximately 200 per 100,000 populations with a mortality rate of 29% , according to the national center for health statistic .\ndifferent components , such as vasogenic and cytotoxic edema and possibly cerebral vasocongestion contribute to posttraumatic brain swelling .\nthis brain swelling is associated with an exponential rise in the icp and eventually leads to brain herniation syndromes . in infants with open sutures ,\nthe relative increases in the icp and their tolerance remain unknown though there is a concern with regards to susceptibility to ischemic injury .\nany fracture extending across the cranial suture in an infant can cause bony separation leading to an open cranial vault .\nlinear skull fracture in association with open sutures can lead to a condition wherein an effect similar to dc is achieved . in adults with a thick solid skull , the linear undisplaced fracture can not expand and therefore probably will not tolerate an increase in icp as well .\nthe 2012 pediatric head injury guidelines state that decompressive craniectomy with duraplasty , leaving the bone flap out , may be considered for pediatric patients with traumatic brain injuries ( tbi ) who are showing early signs of neurological deterioration or herniation .\nhypothesized that early craniotomy ( within 6 h of injury ) in pediatric patients with refractory raised icp would result in better outcomes than following the historic standard of care , which reserved surgery as a final intervention in these patients .\nsimilar studies by kan et al . demonstrated good results with an early craniotomy . in our patient , we believe that the early dc achieved by linear undisplaced fracture and sutural diastasis prevented the development of raised icp leading to quick clinical improvement .\nadelson et al . has recommended the following criteria for selecting favorable patients for craniotomy in children : ( 1 ) diffuse cerebral swelling on cranial ct imaging ; ( 2 ) within 48 h of injury ; ( 3 ) no episodes of sustained icp > 40 mm hg before surgery ; ( 4 ) glasgow coma scale score > 3 at some point subsequent to injury ; ( 5 ) secondary clinical deterioration ; and ( 6 ) evolving cerebral herniation syndrome . while , our patient initially presented with diffuse cerebral swelling on ct , the infant was otherwise neurologically intact and showed no signs of raised icp .\nthus , an emergency surgery was not warranted , and early dural repair was planned .\n. found high rates of bone resorption following autologous bone grafting in pediatric tbi patients similar to our previous experience .\ndue to this and the size of the cranial defect in our patient , we performed the cranioplasty using the titanium mesh plate .\nlinear undisplaced fracture in neonates along with open sutures may act as a dc relieving the raised icp almost immediately .\nsuch infants in whom there are no signs of raised intracranial tension can be managed conservatively if the decompression effect achieved is adequate .\nhence , a close clinical and radiological follow - up is essential . as the effect of decompression", "answer": "decompressive craniotomy ( dc ) is used to treat intracranial hypertension associated with traumatic brain injury . \n early dc is associated with better outcomes . \n we present a neonate with a history of fall with computed tomography scan showing a large frontoparietal contusion and associated parietal and temporal bone fracture . \n this acted as a spontaneous dc causing bony segment to separate due to which the edematous brain could be accommodated . despite the presence of a large contusion , the child was neurologically intact and medically managed . \n the neonate presented with a posttraumatic leptomeningeal cyst 2 months later , which had to be repaired surgically . \n we discuss how a linear undisplaced fracture acts as spontaneous dc and the role of early dc in improving outcomes .", "id": 102} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na presentation to hospital with vertigo or dizziness is common [ 1 , 2 ] .\nthe usual \n reason is disabling dizziness leading to nausea , vomiting , and often prostration \n or inability to mobilise .\npatients with these symptoms are \n challenging with difficulty determining which specialty to refer to .\notolaryngologists have expertise \n in this area ; however , patients may be more appropriately referred to neurologists \n or general physicians in the first instance .\nwe discuss the close interplay of pathophysiology relating to vertigo , \n nystagmus , oscillopsia , and the vestibulo - ocular reflex and its modulation by \n head titubation .\nit may be induced by stimulation of the intact sensorimotor system or \n by dysfunction of any of the stabilising sensory systems .\ngeneral sensations of dizziness , in contrast , are often of \n nonvestibular aetiology . whether this be an impending \n faint ( type ii ) , dysequilibrium ( type iii ) , or vague lightheadedness ( type \n iv ) , it may be due to nonvestibular causes\n. these can include cerebrovascular \n disease , multiple sclerosis , cns tumours , migraine , or epilepsy . \n\t\t\t\na sixty - four - year - old lady presented to her general practitioner \n ( gp ) with acute onset of unsteadiness and dizziness associated with movement .\nshe \n visited her doctor with a complaint of feeling dizzy and faint but had a blood \n pressure of 113/70 mmhg .\nshe had no abnormalities on general , vestibular , \n neurological , and otological examinations , \n including no nystagmus .\nthe dizziness was described as repeated attacks of a sensation \n of internal moving ; that is the patient was whirling , but the room was still . \n\nher symptoms worsened over the \n following week , disturbing her daily activity and leading to nausea , vomiting , \n and prostration .\nthe gp had noted that she had irregular and erratic eye \n movement and had developed a postural drop in her blood pressure , from \n 113/70 mmhg to 97/63 mmhg on standing .\na week later she was permanently dizzy and nauseous and had noticed \n some difficulty in pronunciation of words .\nthe dizziness was now described as a \n constant sensation that she was turning and tilting over , when she knew she was \n upright , and the room was still .\nthere had also \n been the occasional sensation that the room was spinning around , although these \n were the only fleeting .\nshe had no visual disturbance , hearing problems , weakness \n or numbness , and her neurological examination was normal .\nshe was treated with antiemetics including \n prochlorperazine ; with a presumed diagnosis of vestibular failure , and her gp referred \n her to the otolaryngology services for further treatment and to investigate for \n an organic cause . on admission\non \n examination , she was noted to have a subtle head nodding tremor or titubation . \n\nthis was associated with a low - frequency tremor of the upper limbs , which appeared \n to increase on intention .\nshe had erratic eye movements and it was very difficult to elicit any \n nystagmus , even with frenzel glasses , whether spontaneous or positional .\nthis \n was due to the difficulty in keeping her eyes open secondary to overwhelming \n nausea .\nthe patient found that \n it very difficult to keep her eyes still and to focus on a stationary object \n and she was unable to smoothly pursue a moving target .\nthere was clearly a \n fixation instability and it appeared to be in the form of conjugate involuntary \n saccadic oscillations .\nthere was , however , a fleeting vertical nystagmus on upgaze , which may have \n indicated a gaze - evoked cause , but with no obvious horizontal element .\na halmagyi - curthoys head thrust test was \n attempted , but proved difficult to interpret due to the stimulation of \n vomiting .\nit was noted , however , that the patient was unable to fix on a \n stationary object during head rotation indicating a probable suppression of the \n vestibulo - ocular reflex ( vor ) . due to \n the significant nausea and vomiting , a caloric canal test was not performed .\nshe had subtle \n cerebellar signs on subsequent examination , including dysmetria and \n dysdiadocokinesis .\ndix - halpike test was symptomatically \n positive , with vomiting but with no rotatory nystagmus and no positional \n dependence .\nshe was given \n intravenous fluids and steroids and treated symptomatically for the nausea and \n vomiting .\nit was \n postulated that there was a central cause for her symptoms , due to the \n combination of cerebellar signs , fixation instability / opsoclonus , possible \n upbeat nystagmus , and vor suppression .\ntherefore , a magnetic resonance scan ( mri ) \n of the brain was ordered .\nthis revealed a large space - occupying lesion in the \n right lobe of the cerebellum , with a smaller lesion in the left lobe ( figure 1 ) . \n\nthe patient was referred directly to the neurosurgeons who performed a \n suboccipital craniectomy and excision of the cerebellar tumour .\nas a presentation to otolaryngology , the history of this case is not \n unusual .\n, it accounts for 13% of patients , but only 50% of those referred to \n otolaryngology services have an otological cause for their symptoms .\nit can be argued , therefore , that patients presenting with these symptoms should \n be referred to general physicians in the first instance , to rule out serious \n nonotological causes .\nthe anamnesis of dizzy symptoms is especially important to elicit in \n detail in order to make informed decisions on referral route .\nvertigo indicates a sensation of false movement ( generally \n described like a rotation ) , but rarely , the patient can describe it like a sensation \n of tilt . in our case ,\nthe patient described both rotational and tilting sensations , whilst stationary and on \n movement .\nmost importantly was the constant sensation that she was turning but \n that the room was still .\nthis specific symptom , and its duration , \n indicates an increased risk of central origin . with peripheral vestibular causes of vertigo\nthis may be a result \n of oscillopsia , an optical illusion of oscillation sometimes as a direct result \n of nystagmus .\noscillopsia is common in bilateral \n labyrinthine abnormality , but the presence of vertical oscillopsia indicates a \n vertical nystagmus , which is indicative of a central lesion . in this case ,\nspontaneous \n nystagmus , albeit fleeting , was vertical nystagmus and this is particularly \n specific to central lesions rather than peripheral vestibular lesions , and is a \n reliable indicator .\ndamage to the ventral \n tegmental tract , originating in the superior vestibular nucleus , leads to \n upward vestibular signals to the third nerve nucleus and so upbeat nystagmus \n ( ubn ) .\ntherefore , \n a vertical nystagmus should give high index of suspicion for a central cause .\nthe general inability to stabilise the eye , \n resulting in the erratic eye movement and opsoclonus seen may also indicate \n central pathology .\nparticular regions involved are the vermis , flocculus , and paraflocculus , which \n are responsible for coordinating smooth pursuit and adaptation of the \n vestibulo - ocular reflex ( vor ) .\nthese control mechanisms are essential to holding the eye steady for \n fixation , both immediately after saccades and in eccentric positions of gaze , particularly \n important when attempting to track a moving target .\nthe lesions in the cerebellum \n may well have impaired these important mechanisms in this patient , leading to opsoclonus \n and an inability to fixate .\nit is also known that an impairment of adaptation \n of the vor , to compensate for movement , may lead to oscillopsia .\nalthough \n the lesions seen on mri in this case are not in the vermis , surrounding oedema \n and paraneoplastic effects may be responsible for an impairment of vermis \n function .\nthe general difficulty in diagnosis , detailed \n neurotologic examination , and testing in this case may have been influenced by \n the use of prochlorperazine .\nthis is a phenothiazine antipsychotic agent which \n is very commonly used as a vestibular sedative for nausea due to vertigo .\nit is \n widely known , however , although affording symptomatic relief for the patient , \n this drug can result in a delay to vestibular compensation and influence \n diagnostic testing .\nthis is \n defined as nodding head tremor with a frequency of 3 to 4 hz and may be seen in \n midline cerebellar disease [ 12 , 13 ] .\ntitubation can occur in isolation or \n combined with a postural tremor elsewhere , especially in the arms .\nthis can be \n seen in patients with essential tremor or dystonic tremor , associated with \n posterior fossa disorders .\nessential tremor , such as this , is closely related \n to the oculomotor deficits described above . these include deficits of pursuit \n initiation and suppression of the vor .\nit has been shown that there is a strong \n correlation with the intensity of intention tremor and the oculomotor \n impairment and may indicate an impairment of the caudal cerebellar vermis . \n\nthere is the potential , however , that the tremor and head titubation may have \n been an extrapyramidal akathisia as a result of prochlorperazine use .\nthe closely related interplay of the mechanisms involved in this \n patient 's symptoms are \n difficult to sequence .\nthe cerebellar lesions are the only true evidence of a \n causal element to this case .\nhowever , it remains to be understood how these \n lesions had brought about the specific symptom complex identified .\nwas the \n vertigo a direct result of the lesion or was it secondary to an oscillopsia \n generated by nystagmus , or due to failure of the vor ?\nwas ubn or gaze - evoked nystagmus present , or was it just \n a brief recognisable pattern in the otherwise erratic oculomotor impairment or \n opsoclonus , or secondary to loss of adaptation of the vor ? was the head \n titubation the key ?\noscillopsia occurs when there is failure of the vor to \n adapt and compensate for head movements .\ncerebellar lesions may impair the \n normal cerebellar adaptive mechanism for the vor and so impair its ability to \n compensate for movement of the head .\nsimultaneously , a cerebellar lesion may \n also lead to an essential tremor , manifesting as head titubation and upper limb \n tremor .\nmany of the signs seen in this case , such as the impaired vor , the \n titubation , opsoclonus , and dysarthria , are classically caused by cerebellar \n vermal lesions .\nhowever , the lesions seen on mri are in the deeper hemispheres . \n one may , therefore , suggest that surrounding oedema and local compression have led to \n vermal damage .\nit can be seen in figure 1 that there is a degree of cerebellar midline shift .\none may conclude that the lesions themselves may have \n simultaneously caused a tremor and an inability for the vor to compensate for \n it .\noscillopsia due to an impaired vor has been shown to be more likely than oscillopsia due to a titubation . also , the two cerebellar lesions may have had \n the two separate effects of tremor and impaired vor\n. \n\t\t\t the differentiation between central and peripheral causes of vertigo \n can be perplexing and often require the expertise of a specialist \n neurotologist .\nmany signs and tests , such as saccadic pursuit , gaze - evoked \n nystagmus , and the halmagyi - curthoys test , have recently been shown to be \n unreliable in distinguishing peripheral from central causes ; therefore , an \n expert opinion may be required . however , whether the vertigo in this case was \n a result of an oscillopsia , nystagmus , or central cause , the referral route \n should initially be via a general physician to rule out such life threatening \n causes as central tumours .\n\n suspicion of a \n central cause for vertigo on examination should prompt urgent imaging of the \n central nervous system.a vertical nystagmus should give high index of suspicion for a central \n cause.central vestibular lesions may present with a wide variety of symptoms and signs which \n may include impaired vor , head titubation and tremor , opsoclonus , and oscillopsia.initial referral \n of patients with disabling vertigo should be via general physicians . \n \nsuspicion of a \n central cause for vertigo on examination should prompt urgent imaging of the \n central nervous system .\ncentral vestibular lesions may present with a wide variety of symptoms and signs which \n may include impaired vor , head titubation and tremor , opsoclonus , and oscillopsia .", "answer": "objective . discuss complex interplay of pathophysiological effects of cerebellar space occupying lesions on the vestibular pathway . \n discuss challenges of diagnosis and referral along with differential and final diagnosis of unusual presentation . \n case report . \n we describe the case of a patient with vertiginous symptoms complicated by neurological features , namely , head titubation and tremor . \n the patient also had signs of oscillopsia and possible impairment of the vestibulo - ocular reflex . the resulting symptom and sign complex made for a difficult diagnosis , as the interplay of the pathophysiology of these signs , were unusual . conclusion . \n the discussion has revealed that the cerebellar lesions themselves may have simultaneously caused head tremor and an inability for the vestibulo - ocular reflex to compensate , resulting in vertigo . \n however , whether the vertigo was a result of an oscillopsia , nystagmus , or central cause , the referral route should initially be via a general physician to rule out such a life threatening cause as a tumour .", "id": 103} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe grew the budding yeast saccharomyces cerevisiae in 200 l batch culture on bd falcon 96-well microtest plates at 30.7 c ( 0.2c , standard deviation ) using synthetic media ( yeast nitrogen bases + nitrogen , complete supplement mixture ) supplemented with 2% sucrose .\ncultures were maintained in a well - mixed condition by growing on a shaker at 825 r.p.m .\nserial dilutions were performed daily ( 23 hours of growth ) with variable dilution factors .\npopulation densities were recorded each day before the serial dilution by measuring optical density at 600 nm using a thermo scientific varioskan flash multimode reader .\nthe calibration between optical density and cell density was based on the previous characterization of this system . in the group of connected populations , for each dilution factor there were 4 replicate arrays each consisting of 10 patches .\npopulations were connected by controlled dispersal between nearest neighbors ( dispersal rate d=0.5 , which is defined as the fraction of population going out of a patch ) . reflecting boundary conditions\nwere adopted , meaning that a population on the edge would have 75% of its cells remaining in the patch during the dispersal step . in the group of isolated populations ,\nthe experiment was performed in a similar spatial setting except that there was no dispersal ( d=0 ) ; for each dilution factor there were 4 arrays each consisting of 5 patches , thus a total of 20 replicate populations isolated from each other .\nthe dilution factors for the data presented in fig . 2 are 500 , 1000 , 1200 , 1400 and 1600 . in the experiment to measure recovery length ,\npopulations were connected by nearest - neighbor dispersal ( d=0.5 , reflecting boundary conditions ) .\nthe dilution factor for the bad region ( 1 patch ) was 2500 ; the dilution factor for the good region ( 5 patches ) was varied as the environmental driver .\nthe dilution factors for the data presented in fig . 4 are 500 , 750 , 1000 , 1133 , 1200 , 1266 , 1350 and 1400 .\nstatistical indicators for the connected populations were calculated among 10 populations in one array on each day and averaged over a span of at least 5 days , after the populations stabilized .\nthe mean value of 4 replicate arrays and sem ( n=4 ) are shown in figure 2 .\nfor the isolated populations , statistical indicators were calculated on each day among 20 populations over 5 days .\nwe used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .\nthe coefficient of variation ( cv ) was calculated as the sample standard deviation ( supplementary fig .\n3b ) divided by the sample mean . because the local populations in our experiment were grown in a homogeneous environment , in principle they could all be treated as replicates . assuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .\nthe temporal correlation , defined as the lag-1 autocorrelation , was estimated by the pearson s correlation coefficient between the population densities at subsequent days . to correct for negative bias in small samples\nn is a fixed number for different dilution factors , so using the modified estimators would not affect the trend of indicators .\nthe spatial correlation , defined as the two - point correlation between all neighboring pairs , was estimated by the moran s coefficient .\nthe expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 . in the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations\nthe small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate .\nremoving gradient - type spatial heterogeneity before statistical analysis is similar to the detrending procedure commonly used in time - series analysis ; it prevents spurious signals such as positive spatial correlation ( supplementary fig .\nafter the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .\nthe half - point recovery length l was estimated by performing a shape - preserving interpolation ( matlab function pchip , piecewise cubic hermite interpolating polynomial ) to the recovery profile and then locating the position of half recovery at which n(x = lhalf)=12n(x=5 ) .\nthe population density of the bad region ( dilution factor 2500 ) in our experiment was close to 0 ( fig . 4 and supplementary fig .\n7 ) . in the more general scenario with a sharp boundary between two regions of different quality ( supplementary fig . 6 and 8) ,\nthe position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .\nthe exponential recovery length was estimated by fitting an exponential function with three parameters c1 exp(x / l ) + c2 to the recovery profile n(x ) .\nthe data points used for exponential fitting are from position 1 to 5 ( except for dilution factor 500 , the data for fitting are from position 0 to 5 ) .\nwe note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .\n4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile .\nwe grew the budding yeast saccharomyces cerevisiae in 200 l batch culture on bd falcon 96-well microtest plates at 30.7 c ( 0.2c , standard deviation ) using synthetic media ( yeast nitrogen bases + nitrogen , complete supplement mixture ) supplemented with 2% sucrose .\ncultures were maintained in a well - mixed condition by growing on a shaker at 825 r.p.m .\nserial dilutions were performed daily ( 23 hours of growth ) with variable dilution factors .\npopulation densities were recorded each day before the serial dilution by measuring optical density at 600 nm using a thermo scientific varioskan flash multimode reader .\nthe calibration between optical density and cell density was based on the previous characterization of this system . in the group of connected populations , for each dilution factor there were 4 replicate arrays each consisting of 10 patches .\npopulations were connected by controlled dispersal between nearest neighbors ( dispersal rate d=0.5 , which is defined as the fraction of population going out of a patch ) . reflecting boundary conditions\nwere adopted , meaning that a population on the edge would have 75% of its cells remaining in the patch during the dispersal step . in the group of isolated populations ,\nthe experiment was performed in a similar spatial setting except that there was no dispersal ( d=0 ) ; for each dilution factor there were 4 arrays each consisting of 5 patches , thus a total of 20 replicate populations isolated from each other .\nthe dilution factors for the data presented in fig . 2 are 500 , 1000 , 1200 , 1400 and 1600 . in the experiment to measure recovery length ,\npopulations were connected by nearest - neighbor dispersal ( d=0.5 , reflecting boundary conditions ) .\nthe dilution factor for the bad region ( 1 patch ) was 2500 ; the dilution factor for the good region ( 5 patches ) was varied as the environmental driver .\n4 are 500 , 750 , 1000 , 1133 , 1200 , 1266 , 1350 and 1400 .\nstatistical indicators for the connected populations were calculated among 10 populations in one array on each day and averaged over a span of at least 5 days , after the populations stabilized .\nthe mean value of 4 replicate arrays and sem ( n=4 ) are shown in figure 2 .\nfor the isolated populations , statistical indicators were calculated on each day among 20 populations over 5 days .\nwe used bootstrap to compute ses of the indicators by resampling 1000 times the ensemble of replicate populations ( for the coefficient of variation and the temporal correlation ) or arrays ( for the spatial correlation ) .\nthe coefficient of variation ( cv ) was calculated as the sample standard deviation ( supplementary fig .\n3b ) divided by the sample mean . because the local populations in our experiment were grown in a homogeneous environment , in principle they could all be treated as replicates .\nassuming the system is ergodic , the cv calculated over an ensemble of replicates can be interpreted either as spatial cv of many populations at one time point or temporal cv of a single population over many time points .\nthe temporal correlation , defined as the lag-1 autocorrelation , was estimated by the pearson s correlation coefficient between the population densities at subsequent days . to correct for negative bias in small samples\nn is a fixed number for different dilution factors , so using the modified estimators would not affect the trend of indicators .\nthe spatial correlation , defined as the two - point correlation between all neighboring pairs , was estimated by the moran s coefficient .\nthe expectation of moran s coefficient is 1n1 in the absence of spatial correlation ; we used a modified estimator with an additional term 1n1 so that the expectation is 0 . in this case , the sample size n is the number of patches in an array : n=10 for connected populations ; n=5 for isolated populations . for detailed formula of the statistical indicators , see supplementary note 4 .\nin the analysis we ensured environmental homogeneity by removing a linear gradient of population density observed in connected populations .\nthe small gradient is presumably caused by some heterogeneity in experimental conditions ( temperature , dilution errors , etc . ) across the plate .\nremoving gradient - type spatial heterogeneity before statistical analysis is similar to the detrending procedure commonly used in time - series analysis ; it prevents spurious signals such as positive spatial correlation ( supplementary fig .\nafter the recovery profile stabilized , we tracked the population density profiles of at least 6 replicates over several days .\nthe half - point recovery length l was estimated by performing a shape - preserving interpolation ( matlab function pchip , piecewise cubic hermite interpolating polynomial ) to the recovery profile and then locating the position of half recovery at which n(x = lhalf)=12n(x=5 ) .\nthe population density of the bad region ( dilution factor 2500 ) in our experiment was close to 0 ( fig . 4 and supplementary fig .\n7 ) . in the more general scenario with a sharp boundary between two regions of different quality ( supplementary fig . 6 and 8)\n, the position of half recovery can be defined as the midpoint between the equilibrium population density of the region of interest and the population density at the boundary .\nthe exponential recovery length was estimated by fitting an exponential function with three parameters c1 exp(x / l ) + c2 to the recovery profile n(x ) .\nthe data points used for exponential fitting are from position 1 to 5 ( except for dilution factor 500 , the data for fitting are from position 0 to 5 ) .\nwe note that our definition of exponential recovery length is phenomenological , because : 1 ) the deviation is expected to be exponential only close enough to the equilibrium ; 2 ) at higher dilution factors the profile can deviate from an exponential form ( supplementary fig .\n4c ) may be due to the limited data points used in fitting or experimental errors . for both the half - point recovery length and the exponential recovery length , we used bootstrap to compute ses for the indicators by resampling the ensemble of steady - state profiles 100 times and fitting the average recovery profile", "answer": "slower recovery from perturbations near a tipping point and its indirect signatures in fluctuation patterns have been suggested to foreshadow catastrophes in a wide variety of systems1,2 . \n recent studies of populations in the field and in the laboratory have used time - series data to confirm some of the theoretically predicted early warning indicators , such as an increase in recovery time or in the size and timescale of fluctuations36 . \n however , the predictive power of temporal warning signals is limited by the demand for long - term observations . \n large - scale spatial data are more accessible , but the performance of warning signals in spatially extended systems710 needs to be examined empirically3,1113 . here \n we use spatially extended yeast populations , an experimental system displaying a fold bifurcation6 , to evaluate early warning signals based on spatio - temporal fluctuations and to identify a novel warning indicator in space . \n we found that two leading indicators based on fluctuations increased before collapse of connected populations ; however , the magnitude of increase was smaller than that observed in isolated populations , possibly because local variation is reduced by dispersal . \n furthermore , we propose a generic indicator based on deterministic spatial patterns , recovery length . as the spatial counterpart of recovery time14 \n , recovery length is defined as the distance for connected populations to recover from perturbations in space ( e.g. a region of poor quality ) . in our experiments , \n recovery length increased substantially before population collapse , suggesting that the spatial scale of recovery can provide a superior warning signal before tipping points in spatially extended systems .", "id": 104} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe online version of this article ( doi:10.1007/s40121 - 014 - 0043 - 9 ) contains supplementary material , which is available to authorized users .\na member of the togaviridae family , infection with the chikungunya virus ( chikv ) has emerged as a major public health concern , resulting in outbreaks of fever and debilitating arthralgia in the caribbean and globally .\nthe first autochthonous ( native ) transmission of chikv in the caribbean was confirmed in december 2013 on the french island of saint martin .\nrapid spread and local transmission of chikv occurred in the caribbean and the americas within 9 months ( fig . 1 ) .\nthis has resulted in 651,344 suspected and 9,182 laboratory - confirmed chikungunya cases in the caribbean and the americas as reported by the centers for disease control and prevention .\nthe effective management of the rapid spread of chikungunya is integrally related to the geographic distribution and re - emergence of competent mosquito vectors , evolving chikv genotypes , susceptible human populations , environmental influences , and social mobilization .\nunderstanding the contribution of these factors is important to improving the control of the global transmission of this disease.fig . \n1introduction of chikungunya to the caribbean by epidemiological week first reported december 2013 to august 2014 .\ndata from paho / who statistics introduction of chikungunya to the caribbean by epidemiological week first reported december 2013 to august 2014 .\nthere are three distinct chikv genotypes : west african , east central south african [ ecsa ; or indian ocean lineage ( iol ) ] , and asian [ 1 , 5 , 6 ] . these genotypes represent the evolution of the virus in keeping with the geographic distribution over the years . in africa , this virus is transmitted through enzootic ( sylvatic ) and urban ( human mosquito cycle ) cycles among non - human and human primates by aedes mosquitoes species .\nprevious authors report the probable existence of the chikv in africa for hundreds of years , with the first suspected epidemic documented in 1779 .\nsubsequent reports included outbreaks in nigeria ( 1964 ) , the ivory coast ( 1981 ) , and senegal ( 1983 ) associated with the west african strain .\nthe resurgence of chikungunya in the twentieth century was first documented in 1953 , in the newala district of tangaiynika ( tanzania ) .\nthe chikv continued to spread through the suspected vectors aedesfurcifer / aedescordellieri , to other south african countries , inclusive of rhodesia ( zimbabwe ; 1961 , 1962 , and 1971 ) .\nepidemics associated with the ecsa lineage subsequently occurred in cameroon ( 2006 ) and gabon ( 2007 ) with aedesafricanus and aedesalbopictus reported as the principal vectors , respectively . in gabon in 2007 , concurrent chikv and dengue fever epidemics were also experienced , with chikv transmission linked to the a.albopictus mosquito .\nthe iol strain originated in coastal kenya in 2004 and 2005 ( affecting 75% of the lamu island s population , via the vector aedesaegypti ) and then spread to the reunion island ( affecting one - third of the population ) and was subsequently introduced to other islands of the indian ocean and continental india , via the vector a.albopictus [ 1 , 57 , 12 ] .\nit is believed that the 2007 outbreak in italy was initiated through the importation of the chikv by a traveler from reunion island .\nother countries in which international travel facilitated the spread of chikv included france ( from travelers from reunion island ; 77% ) , comoros ( 14% ) , and mauritius ( 9% ) .\nautochthonous transmission in france , however , was not detected until the year 2010 , in association with a. albopictus .\nstudies have reported a high efficiency of transmission of chikv in the temperate climates by the a. albopictus species .\nthere are several aedes species which are competent in the transmission of the chikv , with a.aegypti and emerging populations of a.albopictus identified as responsible vectors in asia .\nthe asian strain identified in thailand in 1958 was transmitted by the suspected vector , a. aegypti .\nthis asian strain was also reported in outbreaks in india ( 19621965 ) and southeast asia ( 19581960 and 19621964 ) , also in association with the a. aegypti mosquito .\nepidemics of the 1980s and 1990s in southeast asian countries ( philippines , thailand , myanmar , and indonesia ) were associated with the asian endemic / epidemic chikv lineage . since then\n, the asian endemic / epidemic chikv lineage has continued to circulate sporadically , transmitted primarily among humans by a.aegypti and was again documented in the 2006 outbreak in malaysia [ 1 , 7 ] .\nemergence of an iol strain with resulting replacement of the endemic asian strain occurred during the southeast asia epidemics of 20062009 [ 1 , 7 ] .\nit is thought that the e1 envelope glycoprotein mutation of the endemic asian genotype resulted in the decreased adaptability of the chikv to a.albopictus , with decreased transmission , and the facilitation of chikv evolution and strain replacement .\nthe caribbean region continues to encounter challenges with the control of mosquito populations including a.aegypti and other aedes species .\nthe aedes mosquito was introduced to the caribbean through the african slave trade . following its introduction ,\na significant increase in the a. aegypti population density was associated with the intercontinental exchange activities of the second world war .\npublic health interventions of national health ministries and the pan american health organization in the 1950s and 1960s successfully reduced a.aegypti vector indexes by 1972 .\nthis success , however , was short lived and the re - infestations of the latin american and caribbean regions by a.aegypti in the late 1970s was accompanied by the introduction of a.albopictus in the early 1980s to some caribbean countries . although both a.aegypti and a.albopictus may be found in the caribbean , a.aegypti remains the principal vector responsible for the transmission of chikv and dengue in this region . to date\n, the chikv lineage identified in the 2014 caribbean outbreak belongs to the old asian lineage .\nthe presence of the asian lineage chikv , compounded by a nave caribbean population and high prevalence of a.aegypti , makes the probability of establishment of endemicity of chikungunya in the caribbean high .\nthis risk of establishment of endemicity extends to most tropical and subtropical regions of latin america areas and the southern usa , which is presently experiencing challenges with a.aegypti re - infestation . in the months preceding the caribbean s first case , china and the philippines accounted for 27.5% of travelers into the caribbean .\nthere were ten cases reported in spain from travelers from haiti and dominica republic during april to june 2014 .\nthe expansion of the chikv to north and south america from the caribbean is of great concern .\nin their review of air travel from the caribbean , noted that the final destination of 52.1% of international travelers from the chikungunya - infected caribbean territories was the usa .\nthe most likely cities to be travelled to from the caribbean were new york ( 13.8% ) , paris ( 11.7% ) , miami ( 7.8% ) and san juan , puerto rico ( 3.9% ) .\nit is expected that the change of climatic conditions , compounded by the increase of the warmer weather in temperate zones , will facilitate the further spread of this disease .\nthe months june through to november are designated as the hurricane season in the caribbean , or the wet season . the wet season has been shown to be associated with the increased breeding of the a.aegypti mosquitos .\nflorida reported its first two cases of autochthonous chikv transmission in july 2014 and , as of september 9 , 2014 , remains the only us state with autochthonous transmission .\nflorida now has eight cases of local transmission and 184 travel - associated laboratory - confirmed chikungunya cases as reported to arbornet .\nthe impact of the introduction of chikv into the caribbean region , a known tourist destination exchange of an estimated 20 million persons annually of which 9 million are us residents , remains to be seen .\nthe acquisition of chikv by travelers to the caribbean enhances the spread to neighboring caribbean countries and globally . as of epidemiological week 35 , among the caribbean countries affected , those with the highest incidence rates ( incidence/100,000 population ) include : guadeloupe ( 16,465 ) , martinique ( 15,087 ) , saint martin ( french part 13,401 ) , saint barthelemy ( 11,707 ) , dominica ( 5,068 ) , dominican republic ( 4,128 ) , and haiti ( 627 ) ( fig . 1 ) .\nthe emergence of chikungunya in the caribbean unfolds a story of the dynamic evolution and interaction of microbes and risk factors underlying the determinants of health .\nthe interaction of economic trade and its role in the transmission of vectors and infectious agents needs to be reviewed and policies reinforced and implemented .\n. continued education to increase the awareness of this disease is needed to curtail the population growth of mosquitoes and to mitigate the spread of chikungunya by travelers to the usa and other regions . improved awareness of the epidemiology and clinical manifestations\npreventative measures and epidemiological monitoring of the evolving chikv epidemic in the caribbean must be improved and sustained .\nthis article does not contain any new studies with human or animal subjects performed by any of the authors . \n\nlizette mowatt and sandra t. jackson have no conflict of interest to declare with respect to this article .\nthis article does not contain any new studies with human or animal subjects performed by any of the authors .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .", "answer": "chikungunya is a mosquito - borne virus that has shown increased prevalence in the caribbean since october 2013 . \n there have been several outbreaks throughout asian and african countries over the past few decades with global travel and tourism having a major impact on the further spread of this disease . improved policies and practices for preventative measures and epidemiological surveillance must be implemented to prevent the continued transmission of chikungunya.electronic supplementary materialthe online version of this article ( doi:10.1007/s40121 - 014 - 0043 - 9 ) contains supplementary material , which is available to authorized users .", "id": 105} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntype 1 diabetes mellitus ( t1 dm ) is one of the most common chronic diseases in childhood and results from autoimmune destruction of pancreatic -cells , leading to insulin deficiency . t1 dm is thought to originate through a combination of genetic and unknown environmental factors , of which environmental factors remain poorly defined .\nnewfoundland and labrador ( nl ) , canada , is recognized as having one of the highest rates of t1 dm worldwide .\na study on hospitalizations of children in nl reported an increase in diabetes - related hospitalizations among children aged 019 years .\nt1 dm is a significant disease in nl with its associated acute and chronic complications as well as the economic costs to both families and the health care system .\nidentification of potential perinatal environmental risk factors is examined in this study to try and elucidate potential reasons of why the disease is so common in this region of north america .\nthis study was a case control design involving the linkage of data extracted from the newfoundland and labrador diabetes database ( nldd ) with the live birth system ( lbs ) .\nthe nldd is maintained by the janeway pediatric research unit at the janeway child health care centre ( jchcc ) in st .\nthe nldd includes data for the majority of cases of t1 dm diagnosed in nl from 1987 to present .\nchildren are included in the database as part of a prospective provincial study on the epidemiology of t1 dm in nl .\nthey have a confirmed diagnosis of t1 dm according to canadian diabetes association ( cda ) criteria .\nthe lbs is maintained by the newfoundland and labrador centre for health information ( nlchi ) .\ndata for this system are acquired from live birth notification forms that are completed in all provincial health care facilities .\nthe forms are provided to nlchi by the vital statistics division , service nl , and contain clinical and demographic data for all births ( resident and nonresident ) in the province .\ncases included children born in nl from 1992 onwards which have been diagnosed with t1 dm before 15 years of age .\nchildren with type 2 diabetes , maturity - onset diabetes of youth , transient hyperglycemia , and diabetes caused by chemotherapy or cystic fibrosis are excluded from the nldd and thus were not included in the study .\nchildren born prior to 1992 were not included in the study because there are no electronic birth notification data available before this date . \na unique identifier , such as the provincial health insurance plan number , was not available for all children in the nldd . as a result case subjects were linked to the lbs using child 's date of birth and mother 's maiden name .\nof the 301 cases in the nldd , 23 were excluded because they were born out of province . of the remaining 278 ,\nlinkage was possible for all but six children resulting in a total of 266 cases included in the study .\nthree control subjects ( n = 798 ) were selected for each case matched on year of birth , sex , and health authority of mother 's residence at time of delivery .\npower analysis was performed to determine whether this sample size would be sufficient to detect statistical significant associations between t1 dm and the risk factors of interest .\nthe power analysis was conducted considering an overall rate of birth by c - section in nl as 30.9% , in order to achieve a power of 80% with a desired odds ratio of 1.5 . using the method described by kelsey et al . \nthe power analysis confirmed that a sample size of 266 cases and 798 controls is sufficient to detect statistically significant relationships between t1 dm and delivery by c - section .\ncases and controls were grouped into two gestational age categories : preterm and term / postterm . birth weight in grams\nwas used to classify cases and controls as high birth weight ( > 4,000 grams ) or not ( 4,000 grams ) .\ncases and controls were also classified as small / appropriate - for - gestational - age or large - for - gestational - age using the method described by kramer et al . .\ncases and controls were grouped according to parity or birth order as either 1 and 2 or more .\nmother 's marital status was categorized as married , single , separated , widowed , or divorced .\nmother 's education level was classified into three categories : not graduated high school , graduated high school , and education beyond high school .\ndemographic and clinical factors of mothers , including age , marital status , education , place of residence , parity ( number of live born children delivered ) , and complications of pregnancy , were included .\ncases and controls were analyzed by sex , place of residence , age of onset , length of gestation , type of delivery , birth weight , size for gestational age , and birth order . \nchi - square tests were used to predict diabetes status on the basis of the independent variables .\nconditional multiple logistic regression was used to assess the relationship between t1 dm risk and the variables of interest .\nthe first model contained birth weight , gestational age , parity , delivery method , mother 's marital status , mother 's education level , mother 's age , maternal hypertension , and mother 's t1 dm status .\nthe second model incorporated all variables in the first model with the exception of birth weight and gestational age which were replaced with size - for - gestational - age .\nbirth weight and gestational age were not included in the same model as size - for - gestational - age as they are components of this variable . the statistical package for the social sciences ( spss ) 17.0\nthis study received approvals from the human investigation committee of memorial university , from each of the hospital boards and the secondary uses committee of the newfoundland and labrador centre for health information ( nlchi ) prior to commencement .\nthe percentages of male and female cases were similar ( 50.8 and 49.2 , resp . ) .\ntable 1 also demonstrates the age distribution of cases as well as their age of diagnosis .\nthere were more males than females diagnosed in the 04 age group ; however , this finding was not statistically significant . \n\ntable 2 presents maternal and perinatal characteristics of the study population . a higher percentage of cases than controls were born pre - term ( 9.8% versus 6.8% , resp . ) .\nwhile there was no significant difference observed between birth weight of the cases and controls , there was a significant difference observed for size - for - gestational - age with a higher percentage of cases than controls born large - for - gestational - age ( 18.2% versus 12.8% , resp .\nit was more common for cases to be delivered by c - section than controls ( 30.8% versus 22.1% , p = 0.009 ) .\nt1 dm was more common among first or second born cases compared to those born third or higher ( p = 0.022 ) . \n\ntable 3 presents the results of the conditional logistic regression models . in the model which included birth weight and gestational age , delivery by c\nchildren delivered by c - section were 1.41 times as likely to develop t1 dm ( hazard ratio ( hr ) 1.41 , p = 0.015 ) . in the second model , which included size - for - gestational - age\n, c - section delivery was not associated with increased risk of t1 dm ( hr 1.3 , p = 0.076 ) . both parity and size - for - gestational - age\nwere found to be significant risk factors for t1 dm from chi - square analysis ( table 2 ) ; these factors did not remain statistically significant in the conditional logistic regression models .\nfindings of this study indicate that c - section delivery was a significant risk factor for t1 dm in children aged 015 years .\nthis finding is in line with a recent meta - analysis of 20 studies which found that the combined effect of c - section delivery was 1.23 ( 95% ci 1.151.32 ) .\ntheories of why this may be associated with the development of t1 dm in offspring includes the involvement of the role of gut bacteria in the development of the immune system .\nstudies have shown a difference between the compositions of gut microbiota in vaginally delivered children and those delivered by c - section .\nchildren delivered by c - section may be primarily exposed to bacteria in the hospital and not maternal bacteria , hence the increased risk of t1 dm may be linked to a different composition of gut flora .\nanother possible explanation is related to the hygiene hypothesis which proposes that the risk of diabetes may be increased when children are not exposed to infections in early life .\nchildren delivered by c - section have decreased exposures to infections compared to children born vaginally and , in turn , have increased risk for diabetes .\nanother theory suggests that the observed increased risk of diabetes after c - section may be related to perinatal stress .\nnl has a high rate of birth by c - section as compared to other regions in canada .\nthe provincial rate of births by c - section was 30.9% in 2005 - 2006 versus the canadian rate of 26.3% .\nthe rates of c - section have increased in nl to 33% in 2010 . in the present study , maternal age at time of birth\nwas not found to be significantly associated with risk of t1 dm in offspring ; other studies have found significant relationships between mother 's age and t1 dm risk .\na recent meta - analysis of 37 studies found that the odds of t1 dm increased by 10% for children whose mothers were over 35 years of age at time of birth ( or = 1.10 95% ci 1.01 , 1.20 ; p = 0.03 ) .\nconversely , a matched case - control study of 196 cases in the united kingdom found that mothers of control children were older than mothers of cases ( or = 0.900 95% ci 0.854 , 0.948 ; p < 0.001 )\n. for other maternal factors , such as education level and marital status , there were no associations found which is consistent with other similar studies [ 14 , 15 ] .\nthe present study also did not find any associations between maternal hypertension and risk of t1 dm in offspring .\nother studies have found an increased risk of t1 dm in offspring with maternal history of t1 dm [ 13 , 16 , 17 ] ; however , these studies also included information on paternal history of t1 dm . a 2009 study by algert and colleagues did not find an association between maternal t1 dm and risk of t1 dm in children .\nsimilar to the present study , the study by algert et al . did not contain information on paternal t1 dm . there was no significant relationship between parity and t1 dm risk found in the current study .\nthis is different than a western australia population based cohort study of 835 cases of t1 dm diagnosed by the age of 15 that found a significant decrease in t1 dm with increasing birth order . \nbirth weight and gestational age were not found to be associated with risk of t1 dm in the present study ; however , chi - squared analysis revealed a significant difference between t1 dm and size - for - gestational - age with a higher percentage of cases than controls born large - for - gestational - age , but this was no longer significant in the conditional logistic regression models .\nour findings do not support the findings of a meta - analysis of 11 studies examining birth weight which found that a birth weight greater than 4,000 grams was associated with an increased odds of t1 dm ( or = 1.17 95% ci 1.09 , 1.26 ; p < 0.05 ) .\nfindings related to the association between gestational age and t1 dm appear to be mixed .\na case - control study conducted in austria found that babies born at 3439 weeks had a significantly higher risk for t1 dm compared to those born before 33 or after 40 weeks .\nhowever , a study by cardwell et al . found that children born after 40 weeks gestation had a significantly lower risk of t1 dm than children born prior to 40 weeks .\nwhile size - for - gestational - age has not been extensively studied , some studies have found significant associations .\na cohort study of 272 children in new south wales , australia , with t1 dm found that children who were small - for - gestational - age had a significantly decreased risk of t1 dm compared to children born appropriate - for - gestational age .\nthe findings of this study should be considered in the context of its strengths and weaknesses .\nan important strength is that the use of a record linkage case - control study design eliminates recall bias that is apparent in cross - sectional study designs .\nsecondly , data contained in the lbs were collected at time of birth by healthcare professionals , and the nldd data were collected from physician charts at time of t1 dm diagnosis which contributes to the reliability of the data .\na limitation of this study is that there was very little information available pertaining to fathers as the majority of the information collected at the time of birth for the lbs is related to the mother and child .\nthis study identified c - section as a significant risk factor for the development of t1 dm among children aged 015 years in nl , a region with very high rates of t1 dm .\nfindings may have an impact on health practice , health care planning and future research related to t1 dm among children .", "answer": "objectives . newfoundland and labrador ( nl ) \n has one of the highest incidences of type 1 diabetes mellitus ( t1 dm ) worldwide . rates of t1 dm are increasing and the search for environmental factors that may be contributing to this increase is continuing . methods . \n this was a population - based case control design involving the linkage of data from a diabetes database with live birth registration data . \n 266 children aged 015 years with t1 dm were compared to age- and gender - matched controls . \n chi - square analysis and multivariate conditional logistic regression were carried out to assess maternal and infant factors ( including maternal age , marital status , education , t1 dm , hypertension , birth order , delivery method , gestational age , size - for - gestational - age , and birth weight ) . \n results . \n cases of t1 dm were more likely to be large - for - gestational - age ( p = 0.024 ) and delivered by c - section ( p = 0.009 ) as compared to controls . \n c - section delivery was associated with increased risk of t1 dm ( hr 1.41 , p = 0.015 ) when birth weight and gestational age were included in the model , but not when size - for - gestational - age was included ( hr 1.3 , p = 0.076 ) . conclusions . \n birth by c - section was found to be a risk factor for the development of t1 dm in a region with high rates of t1 dm and birth by c - section . \n these findings may have an impact on health practice , health care planning , and future research .", "id": 106} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin this issue of critical care , kao and colleagues consider whether open lung biopsy ( olbx ) can assist in the management of patients with acute respiratory distress syndrome ( ards ) .\nclinical outcome in ards remains poor despite substantial advances in our understanding of the biology of this syndrome .\nalthough limiting transpulmonary pressure can clearly prevent worsening of ards , no other major therapeutic advances with proven benefit have occurred in this area .\nprogress has been limited potentially due to the heterogeneous phenotypes that are known to underlie the american european consensus definition of this disease .\nthus , methods to improve diagnostic specificity are likely to be helpful in making progress .\nolbx has been used for years as a method of defining the underlying pathology in patients with lung disease .\nwhile its role has become established in the setting of interstitial lung disease , its utility and safety are more controversial in critically ill patients .\nproponents of olbx argue that knowledge of underlying etiology can be helpful in defining the best course of treatment .\nin addition , the risk of biopsy in experienced hands is fairly low if adequate precautions are taken .\nopponents of olbx cite the lack of specific therapies for underlying etiologies of ards and believe that defining the underlying mechanism of injury is largely academic .\na similar discussion has taken place in the interstitial lung disease arena , where some advocate the demonstration of usual interstitial pneumonitis among patients with idiopathic pulmonary fibrosis , whereas others believe that a therapeutic trial of steroids in the majority of patients is justifiable until new therapeutic strategies emerge .\nthe work by kao and colleagues supports the existing literature that open lung biopsy is fairly safe and frequently revealing in the context of ards .\nfirst , the authors corroborate prior reports that the underlying pathology in clinical ards is often a pattern other than diffuse alveolar damage or fibro - proliferation . of note ,\nthis and prior studies were retrospective analyses making the generalizability of these findings difficult to define . without knowing the total number of ards cases potentially eligible for biopsy\n, we have no easy way to know how common the observed abnormalities would be in an unselected ards population .\nsecond , the authors found minimal morbidity attributable to the surgical procedures that their patients underwent .\nthese data support the existing literature that , in experienced hands , olbx can be safely performed in carefully chosen patients .\nthe risk of bronchopleural fistula was fairly low in the present study , which may reflect the use of protective mechanical ventilation .\nwe have recently observed that high pressures measured at the airway opening are strongly predictive of prolonged bronchopleural fistula risk following lung biopsy in ards .\nthus , attention to mechanical ventilator settings may be one factor that led to the low risk of this procedure .\nnearly 75% of patients had changes made in their therapeutic management due to findings from olbx . whether these changes were helpful to the patient is not entirely clear due to the lack of a control group\nhowever , at least 14 patients ( 11 with infections , 1 with hypersensitivity pneumonitis , and 2 with pulmonary edema ) had a disorder found for which accepted therapies exist .\ninterestingly , the most common change in management recorded in response to olbx results was the institution of glucocorticoid therapy .\nthe role of glucocorticoid therapy in ards has been controversial , with some smaller studies showing benefits whereas other larger studies demonstrated no important benefit .\na number of critiques have emerged after the recently published new england journal of medicine trial examining the role of steroids in persistent ards , leading some to speculate that , despite the negative results of that trial , some ards patients may still benefit from anti - inflammatory therapy . in this recent study , more than 95% of patients\nwere excluded prior to enrollment , leading to results that may not be generalizable to the overall ards population .\nthe most common reason for exclusion was glucocorticoid therapy , yielding the possibility that the best candidates for steroid therapy ( from both an efficacy and safety perspective ) were excluded from the study .\nin addition , the frequent use of paralytics ( in up to 50% of steroid treated participants ) and marked hyperglycemia ( mean values in excess of 200 mg / dl ) may have contributed to avoidable complications of steroid therapy .\nthus , the frequent re - intubations and neuromyopathies that occurred in this recent study may have offset the potential benefits of steroid therapy .\nregardless , the stratification of patients likely to benefit from steroid therapy , while avoiding the potential morbidity of pharmacological therapies and other intensive care unit measures ( including mechanical ventilation ) is likely to be a successful strategy .\nfuture studies that aggressively limit the side effects of steroids and that examine treatment response stratified by olbx findings may demonstrate subgroups of patients that derive important benefit from this therapy . in the future ,\nbiomarkers that could be defined either in the serum or by bronchoalveolar lavage would be preferable to olbx to stratify the likelihood of benefit from steroid therapy .\nsuch biomarkers may help define the underlying pathobiology and so become a surrogate for olbx in assessing the steroid responsiveness of the disease .\nanother class of biomarkers that may prove useful in the management of ards patients would be ones that provided information on the intrinsic steroid responsiveness of the patient .\nthe search for genetic polymorphisms that predict individual responsiveness to steroid therapies is well underway in other conditions such as asthma and ulcerative colitis .\nboth types of biomarkers would aid treatment decisions by better defining subgroups most likely to benefit from steroid therapy .\nthus , further work is clearly needed to determine whether individualized therapy will improve outcome in various subgroups of ards patients .", "answer": "progress in the treatment of acute respiratory distress syndrome ( ards ) has been slow , perhaps in part due to the heterogeneity in the biology underlying this syndrome . \n open lung biopsy is a feasible approach to define various subcategories of underlying histology . in experienced hands , with careful selection of patients and close attention to details of critical care management , including mechanical ventilator settings , the procedure is safe even in patients with severe disease . \n however , further work is needed to define which patients , if any , experience a beneficial effect on outcome from this procedure . \n more research is needed on assessing efficacy of potential therapies within histologically defined subgroups . in the future \n , various biomarkers may be available to non - invasively classify ards patients from the standpoint of responsiveness to various therapies , such as gluco - corticoids .", "id": 107} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndifferent factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine .\nour aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine .\nin this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences .\nwe also evaluated the texts on physical activity and genetics in pubmed and google scholar .\nthe results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior .\nit is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj .\nthe results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity .\nsuch categorization would be helpful in identifying illnesses due to sedentary life in special groups of people .", "answer": "background : different factors , especially genetic , effect individual attitude to regular physical activity in iranian traditional medicine . \n it was believed that individual physical activity attitude is affected by mizaj too . \n our aim was to conduct a comparative revision and evaluation of the effect of genetic factors on physical activity in classic medicine and iranian traditional medicine.methods:in this study , we reviewed persian resources in the research center of traditional medicine at shiraz university of medical sciences . \n we also evaluated the texts on physical activity and genetics in pubmed and google scholar.results:the results of classical medicine revision showed the effect of especial genes on obesity and sedentary behavior . \n it is also derived from iranian traditional medicine resources that physical activity and sedentary behavior is affected by individual mizaj.conclusion:the results showed that those with hot and cold mizaj have different genetic potentials in sedentary behavior and physical activity . \n such categorization would be helpful in identifying illnesses due to sedentary life in special groups of people . \n it would also allow designing dedicated treatment for each person .", "id": 108} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninstitutional review board approval was obtained from the wake forest university , and informed consent forms were completed for all participants .\nitems for four concepts identified in the literature were glucose control , well - being and side - effects , lifestyle burden , and treatment complexity and convenience and were evaluated in a series of five focus groups made up of five to eight patients drawn from an evaluation study of community diabetes clinics in north carolina ( 11 ) .\nparticipants were male and female and white and nonwhite with simple and complex medication regimens and a1c levels that ranged from well controlled to uncontrolled .\nthe resulting 35-item prototype instrument was administered by mail to a convenience sample of 75 patients ( the exploratory sample ) , who were treated with diabetes medications at our study community - care site , to assess item reliability , mean and distribution , redundancy or uniqueness , skewness , and construct validity .\nalso examined were item correlations with a1c level , the multidimensional diabetes questionnaire ( 12 ) lifestyle interference scale , the medical outcomes studies ( mos ) health worries scale score ( 13 ) , and global items assessing extent that blood glucose has been unacceptably high or low . an item performance score was constructed ( 0 , weak ; 1 , moderate ; or 2 , ideal performance ) to guide item retention .\nfifty - five ( 73% ) patients completed the survey , and nine items were removed based on skewness or redundancy ( r > 0.75 ) with other items . in the initial test sample\n, patients of a large family - medicine practice treated for diabetes with a recent a1c value within the last 3 months ( the evaluation sample ) were invited to complete the study survey packet including the revised 26-item instrument and validation instrument described above .\nmedication complexity was assessed using a score of 0 or 1 ( no / yes ) for common diabetes medications and a score of 0 or 2 ( no / yes ) for insulin , a more demanding regimen .\nself - reported adherence to medications was by recall of skipped or missed doses over the last 10 days .\npackets were mailed to patients with instructions and a voucher for a 25 usd gift certificate .\nexploratory factor analysis ( efa ) of the dmsat items was conducted using sas ( version 8 ; sas , cary , nc ) to assess whether the common factor model was appropriate ( 14 ) based on kaiser 's sampling adequacy , scree plot , and model fit .\ndiscriminant validity of the dmsat was examined by comparing means across levels of a1c ( < 8% and 8% ) , treatment complexity ( low and high ) , self - reported adherence , and mos health worries . for the final test sample ,\nanother sample of patients from our community diabetes care clinics ( 11 ) and from an academic medical center was recruited to conduct and evaluate confirmatory factor analysis of the dmsat and confirm validity\nin the evaluation sample , 194 ( 63% ) of 307 eligible patients returned the survey packet ; of these , 140 reported current medication use .\nparticipants had a mean age of 63 years , and most had completed high school ( 77% ) and had been diagnosed with diabetes at least 5 years previously ( 61% ) .\none - third ( 2939% ) were taking one , two , or three medications for diabetes , with 16% taking insulin ; 14% had a recent a1c > 8.0% , and 19% rated their adherence to their medication regimen in the last 10 days as less than complete .\nten items displayed high inter - item correlations ( > 0.75 ) and were removed .\ninitial factor analysis of the reduced 16-item questionnaire identified a four - factor structure consistent with our domains of lifestyle , medical control , convenience , and well - being and explained 75% of the total variance .\nas shown in table 1 , dmsat scales and total score discriminated ( p < 0.05 ) between high and low levels of treatment complexity , self - rated glucose control , mos health worries scale score , and clinical value for recent a1c ( < 8% vs. 8% ) in the expected direction .\ncorrelation of the dmsat scores with continuous a1c values was 0.24 ( p = 0.0049 ) . in the final , confirmatory sample ,\nas shown in table 1 , dmsat scales and total scores discriminated between validity groups as in the previous sample and were highly correlated with the dtsq ( r = 0.68 ; p < 0.001 ) . unlike the dmsat , the dtsq total score did not discriminate between levels of treatment complexity and clinical a1c value .\nthe dmsat is intended as a brief measure of diabetes medication treatment satisfaction and discriminates between important correlates of patient management .\nit performed as well as the dtsq in detecting self - rated glucose control and health worries but showed superior properties in correspondence with treatment complexity and a1c .\nnote that appraisals of cost of medications or specific side effects that may be caused by diabetes or its treatment , such as diminished sexual functioning , bloating , or weight gain , are not separately assessed and may require assessment elsewhere .\n, we believe that the 16-item dmsat offers a comprehensive assessment of satisfaction with diabetes therapy and may aid in individualizing patient diabetes treatment .", "answer": "objective to develop and test a patient questionnaire on treatment satisfaction with diabetes regimens.research design and methods survey items were developed from community clinic focus groups , pretested in patients with diabetes , and examined in two samples of treated patients.resultssixteen items performed well in assessing treatment experiences : ease and convenience , lifestyle burdens , well - being , and medical control . \n construct validity was supported by associations ( p < 0.05 ) with treatment complexity , self - rated glucose control , health worries , and a1c . \n internal consistency ranged from 0.89 to 0.95.conclusionsthe diabetes medication satisfaction tool offers a comprehensive assessment of patient acceptability , with diabetes therapy useful for individualizing therapeutic decision making .", "id": 109} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbreast - conserving surgery and radiation therapy are the standard alternatives to mastectomy for eligible women with stage 0 , i , or ii breast cancer [ 1 , 2 ] .\nsurvival outcomes are equivalent to women who undergo initial mastectomy , and the long - term rates of ipsilateral breast tumor recurrence ( ibtr ) are on the order of 5% to 15% [ 36 ] . for those who develop a clinically isolated ibtr after breast - conserving surgery and whole - breast radiation , salvage mastectomy\nthree - quarters of local recurrences are clinically solitary [ 7 , 8 ] , with an average size of 1 - 2 cm [ 914 ] . therefore , many ibtr appear amenable to additional attempts at breast - conserving surgery .\nbreast conservation has many potential benefits on patient self - image , sexuality , and quality of life compared to mastectomy .\nhowever , second attempts at breast conservation with surgery alone have been associated with high risks of second ibtr of 1848% [ 13 , 1619 ] .\narguments against reirradiation to improve local control include concerns for radiation resistance of the recurrent tumor , acute toxicity , poor cosmesis , or risk of serious late effects .\nit is not possible from the few available retrospective studies of external beam boost radiation to conclude whether local control after salvage breast conservation surgery is improved by conventional re - irradiation [ 16 , 20 , 21 ] .\nhowever , the rationale for postexcision radiation should be the same as in the initial adjuvant setting to address the risk for microscopic residual disease in the region of the excision cavity that exists even when surgical margins are negative . and\nthese early reports have demonstrated low risks of complications in selected patients . accelerated partial breast irradiation ( apbi ) is radiation confined to the immediate area around an excision cavity rather than to the whole breast volume . in the setting of a clinical trial , apbi has been proposed as an alternative to salvage mastectomy for selected patients with favorable ibtr after breast - conserving surgery and whole - breast irradiation [ 21 , 22 ] .\napbi has the potential of improving local tumor control compared to breast - conserving surgery alone .\nthe use of hypofractionation and the accelerated treatment time with pbi could improve the tumor control of tumors that have recurred after prior conventional 2 gy fractionation by overcoming effects of intrinsic radioresistance , repair or rapid repopulation .\napbi may reduce risk of toxicity of conventional re - irradiation by limiting the volume of breast tissue and neighboring normal tissue treated to high cumulative doses .\nproper patient selection for an ibtr of limited extent and favorable biology would be essential for treatment by apbi to have a chance of securing local control . a favorable profile of ibtr for such a trial of apbi would need to include isolated recurrences that are unifocal and limited in size so that a repeat breast - conserving surgery could obtain negative margins and maintain good cosmesis .\nin addition , the area of involvement would need to be limited in size without multifocality or multicentricity for a focused treatment such as apbi to have a reasonable chance for local control .\ntumors with a short interval to recurrence after radiation , less than 2 years being a typical cutoff , would more likely have an aggressive biology with a poorer prognosis due to a high incidence of systemic progression [ 6 , 19 ] .\nto better identify candidates who could have been eligible for a salvage apbi protocol , we studied the clinical and pathologic characteristics of 157 ibtrs after salvage mastectomy to identify factors associated with a favorable recurrence profile .\nwe retrospectively reviewed a prospective database of 3310 consecutive women with early - stage breast cancer treated with breast - conserving surgery and radiation therapy from 1980 to 2005 .\npatient demographics , tumor characteristics , and treatment - related information were entered prospectively and the data were maintained and updated by a single data manager .\nthe collection , storage , and retrieval of data were done in compliance with the hospital 's institutional review board and the health insurance privacy and portability act .\ninclusion criteria for this study were primary breast cancer ; american joint committee on cancer 6th edition initial cancer stages 0 , i , or ii ; initial treatment with whole breast radiation therapy ; a clinically isolated ibtr ; and treatment for ibtr by mastectomy .\nexclusion criteria included male breast cancer , t3-t4 disease , stage iv disease , mastectomy for initial treatment , and no radiation therapy as part of the patient 's initial treatment .\nall patients were treated initially by breast - conserving surgery followed by whole - breast radiation ( 4650 gy ) , with or without regional nodal radiation , and a boost to the tumor bed ( 1018 gy ) .\nthe total dose was generally determined by the final margin status after lumpectomy : 60 gy for a negative margin , 64 gy for a close margin , and 66 gy for a positive final margin . \nthe study endpoint was a classification as a favorable ibtr defined as an isolated first site of recurrence ; unifocal ; invasive or in situ ; less than or equal to 2 cm in size ; no skin involvement ; and more than 2 years from initial treatment .\nchi - square test , wilcoxon 's test , and generalized estimating equations were used for univariate and multivariate analyses .\nthe characteristics of the 157 patients in the study population are summarized in table 1 . at the time of their initial diagnosis and treatment\npatients were approximately equally divided between pre- and postmenopausal status and laterality of the breast cancer .\nthe interval to recurrence was 2 years in 8% and > 2 years in 92% .\nibtr was confined to the same quadrant as the initial tumor in 55% of patients , a different quadrant in 33% , was diffuse or multicentric in 6% , and skin was involved in 3% .\nhistologically , most patients presented with invasive ductal carcinoma ( 77% of primary tumors and 57% of ibtr ) . receptor status was considered hormone sensitive ( er or pr positive ) or insensitive ( er and pr negative ) .\nthis was available for only 39% of the ibtr compared to 72% of the initial tumors .\nthe differences in characteristics between the initial tumor compared to the subsequent ibtr are shown in table 3 .\nthere were more palpable tumors at time of initial diagnosis ( 55% ) compared with ibtr ( 41% ) .\nthe method of detection was physical examination only in approximately 20% at time of initial diagnosis and ibtr .\nmore ibtr were detectable on mammogram alone compared to the initial tumors ( 55% versus 40% ) .\npathologic t stage at initial diagnosis and clinical t stage of ibtr were predominantly t1 , 65% and 57% , respectively . among patients with known receptors ,\nthe percentage of hormone sensitive tumors was 78% of initial tumors and 67% of ibtr ( table 3 ) .\nfor patients initially hormone sensitive , the ibtrs was hormone sensitive in 37 of 41 ( 90% ) . for patients known to be initially hormone insensitive ,\nthe ibtr was sensitive in 9 of 20 ( 45% ) . among the 90 patients with a clinical t1 ibtr , pathology from salvage mastectomy was available for 75 patients . in 71 of 75 patients ( 95% ) with clinical t1 ibtr\nfor those with pathologic data , the ibtr were clinical stage t1 or dcis in 77% and pathologic tis or t1 in 70% .\nthe median tumor size at time of both initial diagnosis and ibtr was 1 cm .\nthe characteristics of the initial tumor versus the ibtr were analyzed to determine predictors of pathologic t1 size at time of salvage mastectomy .\nthere was no significant correlation between the studied initial tumor characteristics and subsequent pathological size of ibtr .\nclinical t stage at recurrence was the only independent predictor of having a t1 pathologic recurrence stage .\napproximately 1020% of patients with stage i or ii invasive breast cancer will develop an ibtr by 10 years after breast - conserving surgery and rt [ 36 , 2428 ] .\nin general , ibtr rates have been decreasing due to improvements in patient selection for initial treatment with breast - conserving surgery and whole breast radiotherapy , surgical and radiation techniques , and the use of systemic therapy [ 29 , 30 ] .\nour study population of only 157 ibtr from an initial population of over 3,000 patients ( less than 5% ) after a median followup of 140 months is consistent with this reported decreasing risk of ibtr in other studies .\ncurrent recommendations for surveillance of patients following breast - conserving therapy include monthly patient self - examination , examination by a physician every 4 to 6 months for 5 years and then annually , and mammography 6 months after radiation and then annually . in the current study\n, we found that 80% of ibtr were detectable on mammography , and the median size was 1 cm .\nwe have insufficient numbers of patients with ibtr t2 or larger to analyze for significant characteristics that could be prospectively identified .\nif there were a common independent factor that predicted for a large size of ibtr with current methods of physical examination and mammography , then a more intensive surveillance could be recommended for such patients .\nmastectomy is the standard treatment for patients with a clinically isolated ibtr after whole - breast irradiation .\nsalvage mastectomy is associated with local control rates of approximately 8595% [ 8 , 13 , 17 , 19 , 3134 ] . a change in this paradigm for salvage\ntherapy needs to be approached with caution so that new treatments for ibtr with lower rates of local control do not become commonplace .\nhowever , in the setting of a clinical trial , for women who find mastectomy unacceptable or are medically poor candidates , identification of other salvage treatment modalities for ibtr may be appropriate .\nhowever , second attempts at breast conservation with surgery alone have been associated with high risks of second ibtr of 1848% [ 13 , 1619 ] .\nthere is a limited published experience with giving further rt after prior whole - breast irradiation after salvage breast - conserving surgery for ibtr . in the study of kurtz et al .\n, 11 of 50 patients who had recurrences away from the original tumor bed were given additional radiation after wide excision .\nsecond local failures occurred in 36% of the patients treated with further irradiation , compared with 31% of those treated with wide local excision alone .\ndeutsch and colleagues reported on a series of 39 women treated for ibtr by repeat wide local excision and treatment to an electron field around the lumpectomy bed with an additional 50 gy .\nthere were no reported serious sequelae from the additional radiation . in the setting of a clinical trial ,\napbi has been proposed as an alternative to salvage mastectomy for selected patients with favorable ibtr after breast - conserving surgery and whole - breast irradiation [ 21 , 22 ] .\nhannoun - levi et al . reported on 69 patients with ibtr who were treated by a second breast - conservation surgery and interstitial brachytherapy .\nfactors associated with better local control were an interval to recurrence of 36 months or greater and use of a greater number of catheters for the implant .\nthis suggests that improved methods of radiation technique that optimize dose coverage may lead to better rates of local control in future studies .\nin addition to optimized apbi techniques , improved patient selection could result in improved rates of local control after salvage breast conservation for ibtr . a favorable profile of ibtr for apbi would need to be isolated , unifocal , and limited in size .\nselection of tumors with a longer interval to recurrence would also include ibtr with less aggressive biology and patients with better chances for long - term survival .\nwe identified approximately 70% of patients with these favorable ibtr characteristics after initial breast - conserving surgery and whole - breast radiation .\nthe clinical estimation of tumor size was the most significant independent factor predictive of having pathologically confirmed favorable ibtr at salvage mastectomy .\nthis favorable subset of patients could be a pool of eligible candidates for a clinical trial of salvage breast conservation in this setting .\nthe radiation therapy oncology group is currently studying salvage breast - conserving surgery and apbi in this favorable subset of patients .\npatient selection includes ibtr 3 cm or less in size , without imaging evidence of multicentricity , and an interval to recurrence of greater than 1 year .\nour data suggests that over 70% of patients with ibtr will be eligible for enrollment given that our selection criteria for most favorable ibtr are more strict than the rtog trial eligibility .", "answer": "background and objectives . accelerated partial breast irradiation ( apbi ) has been proposed as an alternative to salvage mastectomy for patients with ipsilateral breast tumor recurrence ( ibtr ) after prior breast conservation . \n we studied factors that are associated with a more favorable local recurrence profile that could make certain patients eligible for apbi . methods . between 1980 and 2005 , 157 stage 0ii breast cancer patients had an ibtr treated by mastectomy . \n clinical and pathological features were analyzed to identify factors associated with favorable ibtr defined as unifocal dcis or t1 2 cm , without skin involvement , and > 2 year interval from initial treatment . \n results . \n median followup was 140 months and time to recurrence was 73 months . \n clinical stage distribution at recurrence was dcis in 32 pts ( 20% ) , t1 in 90 pts ( 57% ) , t2 in 14 pts ( 9% ) , t3 in 4 pts ( 3% ) , and t4 in 9 pts ( 6% ) . \n ibtr was classified as favorable in 71% . \n clinical stage of ibtr predicted for pathologic stage 95% of patients with clinical t1 ibtr had pathologic t1 disease at salvage mastectomy ( p < 0.0001 ) . \n \n conclusions . \n clinical stage at presentation strongly correlated with pathologic stage at mastectomy . \n more than 70% of recurrences were favorable and may be appropriate candidates for salvage apbi trials .", "id": 110} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na retrospective review of clinical records of late postpartum eclampsia patients who had presented with acute onset of visual and/or neurological symptoms to the emergency department of a medical college hospital in south india between april 2009 and may 2013 was done .\nall patients had underwent mri with diffusion weighted imaging ( dwi ) and apparent diffusion coefficient ( adc ) mapping to differentiate vasogenic from cytotoxic cerebral edema .\npatient records were analyzed for presence of visual symptoms , peak systolic and diastolic blood pressures , associated neurological symptoms , location of mri lesions and time taken for recovery .\nthe mr images were graded for extent and severity of cortex and white matter vasogenic edema , degree of confluence , mass effect and ventricular distortion on a scale from 1 to 5 .\nstatistical analysis was performed using chi - square test and a p value of less than 0.05 was considered to be statistically significant .\nclinical and imaging findings are summarized in table 1 . clinical profile of patients with pres the 10 patients ranged in age from 21 to 32 years ( average-26 3.49 years ) .\nmean peak systolic and diastolic blood pressures were 144 21.71 and 93 9.19 mm of hg , respectively .\nbilateral visual loss was noted in five patients of whom three patients were able to perceive hand movements and two patients had only perception of light .\nthe most common abnormality noted on mri included bilateral symmetrical hyperintensities on t2-weighted images and fluid attenuated inversion recovery ( flair ) sequences in the parieto - occipital regions [ figs . 1 and 2 ] .\ndwi showed high signal intensity with no areas of restricted diffusion while adc mapping did not show corresponding low signal intensity thus suggesting vasogenic edema .\naxial mr image ( fluid attenuated inversion recovery ) showing confluent edema in subcortical and deep white matter ( grade 4 ) seen as hyperintensities in bilateral parieto - occipital lobes ( patient 6 ) axial mr image ( fluid attenuation inversion recovery ) showing edema in subcortical white matter ( grade 2 ) seen as hyperintensities in bilateral occipital lobes ( patient 9 ) five patients had additional abnormalities in the cerebellar hemispheres and three patients had involvement of frontal lobes . average time taken for visual recovery was 2.6 1.34 days .\nfollow - up mri in four patients after 1 month revealed complete resolution of these abnormalities . in the remaining , clinical symptoms and signs\nfollow - up scans were not performed due to financial constraints . the extent of cerebral edema in patients with and without visual loss was compared and results summarized in table 2 .\nposterior reversible encephalopathy syndrome ( pres ) is a rare neurotoxic state that presents with altered mental status , headache , seizures , and visual disturbances along with neuroimaging features of vasogenic edema involving the posterior cerebral circulation .\nalthough several cases of pres have been reported in neurology and neuroradiology literature , exposure in ophthalmic literature has been rather limited .\nthe causes of pres are diverse and include pre - eclampsia , eclampsia , renal insufficiency , solid organ transplantation and immunosuppressive therapy .\nhypertensive encephalopathy is said to be the cause of this syndrome which has been demonstrated by various clinical and experimental studies .\npatients with hypertensive encephalopathy have the same clinical signs as those with pres and they also have rapid resolution of clinical and imaging abnormalities once the blood pressure is lowered .\nthe most widely accepted theory states that sudden elevation of blood pressure causes failure of autoregulation in the cerebral blood vessels leading to hyperperfusion , breakdown of blood brain barrier , and vasogenic edema . the posterior circulation is preferentially affected since it has less sympathetic innervation than the carotid circulation , thus rendering it less able to adjust to blood pressure fluctuations . however , this theory is not comprehensive because pres can affect normotensives .\nhigh degree of suspicion is required in these patients of late postpartum eclampsia because it occurs between 48 hours postpartum and 1 month after delivery frequently in women who have had a normal pregnancy and delivery and no signs of a pre - eclamptic syndrome .\nalternative theory implicates endothelial dysfunction as the cause for occurrence of pres in eclampsia and sepsis .\nthis is supported by the fact that elevations in markers of endothelial dysfunction such as lactate dehydrogenase and abnormal red blood cell fragmentation have been reported in pres .\nvasospasm with subsequent ischemia has also been hypothesized to cause loss of integrity of the blood brain barrier in eclampsia .\nalthough reversible by definition early recognition and prompt treatment is essential to prevent secondary complications like intracerebral hemorrhage and infarction .\na large retrospective study of pres in diverse clinical situations revealed the occurrence of visual symptoms in 20% and headache in 26% while seizures was observed in 74% of cases .\nthe visual disturbances reported with pres include cortical blindness , visual neglect , homonymous hemianopia and blurred vision .\ncortical visual loss was observed in five of our patients ( 50% ) while the remaining denied any visual disturbances .\nour findings are in line with liman et al . , who observed that visual disturbances like cortical blindness , blurred vision and hemianopia are more common in eclampsia related pres ( 50% ) .\npatients with pres due to other etiologies more often present with severe symptoms like altered mental status or neurological deficit and lesser visual disturbances ( 27.8% ) .\nroth et al . , have also reported a higher percentage of disturbed vision in pre - eclampsia - eclampsia - related pres .\nthis could be because of the younger age and lesser associated comorbidities in these patients as compared to patients with pres due to other etiologies .\nall patients ( with / without visual loss ) demonstrated bilateral symmetrical hyperintensities in the parieto - occipital regions on t2-weighted images .\nthis feature along with predominant involvement of the white matter distinguishes this syndrome from bilateral posterior cerebral artery territory infarction .\nalthough several studies have reported visual symptoms of varying degrees in pres , to the best of our knowledge no study has attempted to correlate the visual symptoms with imaging abnormalities .\nthe limitations of our study include its retrospective design , and smaller sample size of postpartum eclampsia patients .\nwe conclude that there is a higher prevalence of cortical visual loss in patients with pres associated with late postpartum eclampsia .\npatients with higher degree of vasogenic edema of the posterior cerebral white matter might present with visual loss .\nophthalmologists should be aware of this clinical entity since it is reversible and readily treated by controlling the blood pressure .\nfurther prospective studies comprising larger sample size and different etiologies of pres are warranted in this regard .", "answer": "the purpose of this study was to determine the prevalence of visual disturbances in patients with posterior reversible encephalopathy syndrome ( pres ) associated with late postpartum eclampsia . \n we retrospectively reviewed the clinical records of late postpartum eclampsia patients with features of pres for the presence of visual disturbances and location of radiological abnormalities . \n we found a higher prevalence of cortical visual loss in patients with pres associated with late postpartum eclampsia . \n bilateral symmetrical vasogenic edema of the parieto - occipital lobe was the most common magnetic resonance imaging ( mri ) abnormality noted . \n no significant differences were observed in the extent of edema in patients with and without visual loss .", "id": 111} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin february 2012 , the birmingham and solihull tb service noted 2 distinct 24-loci miru - vntr strain types of mycobacterium tuberculosis ( clusters a and b ) isolated from 4 eritrea - born patients with pulmonary tb .\nthe diagnoses were made in july ( cluster a ) and december 2011 ( cluster b ) .\nepidemiologic links were considered to be patients naming each other as contacts , sharing a contact without naming each other , or sharing a location during the infectious period of 1 patient .\ncase managers interviewed patients to elicit names of persons they may have had regular contact with over the infectious period ; contacts in nonhousehold settings ( e.g. , workplace , leisure sites ) were also included , but geographic locations were not always defined .\nthe infectious period was defined as the date of onset of respiratory symptoms , if known , or 3 months before diagnosis .\nsurveillance data revealed an increased number of eritrea - born tb patients ( 1 , 4 , and 19 cases in 2004 , 2006 , and 2011 respectively ) ; estimated incidence was 960 cases per 100,000 persons . to investigate whether transmission had occurred in the united kingdom and to identify opportunities for wider community intervention , we invited all eritrea - born tb patients ( with and without strain typing available ) reported during 2004august 2012 for an extended interview with a dedicated tb nurse .\nsemistructured questions examined potential sources of infection and secondary cases . to systematically explore locations frequented by patients ,\nnurses asked patients to complete a 24-hour work / rest / play diary . since november 2011\n, extended interviews have been routinely conducted for all miru - vntr clustered tb patients in birmingham ; no ethics approval was required . according to routine practice , clustered eritrea - born patients continued to be interviewed through december 2013 .\nmost patients were male ( 65% ) and had pulmonary tb ( 67% ) ; median age was 29 ( interquartile range 2535 ) years , and median length of time in the united kingdom before diagnosis was 4 ( interquartile range 25 ) years .\nof 62 ( 71% ) patients who could be located , 49 participated in extended interviews . except for homelessness ( 1 patient ) , no other social risk factors ( e.g. , drug and/or alcohol misuse , imprisonment , or mental health problems ) were noted .\nsocializing occurred mainly in places of worship ( 43/49 patients frequented 9 places of worship ) and private homes ( 10/49 patients frequented 7 residences ) .\nmiru - vntr typing was available for all 61 culture - confirmed cases ; 46 isolates had 24 loci , and 15 isolates had 15 loci ( table 1 ) .\nof the isolates with 24 loci , 27 ( 59% ) clustered in 6 strain types . to identify risk factors for strain - type clustering , we compared demographic characteristics of clustered and nonclustered patients ( table 2 ) . according to bivariable analysis results ,\na noncongregate location was significantly associated with cluster a only ( table 2 ) . * miru - vntr , mycobacterial interspersed repetitive units variable - number tandem - repeat ; na , not applicable . \nno epidemiologic links between those from different countries were found except in cluster e. 15-loci miru - vntr typing was available beginning in 2003 . \niqr , interquartile range ; bcg , bacillus calmette - gurin ; miru - vntr , mycobacterial interspersed repetitive units variable - number tandem - repeat ; na , not applicable ; rv , religious venue ; tb , tuberculosis . fisher exact test ,\nthe figure shows the overlap of social networks and miru - vntr strain - type clusters for eritrea - born tb patients .\nfew cases were linked by routine contact investigation alone because patients named the place of congregation ( designated as religious venue [ rv ] 1 in the figure ) in different ways .\nthe extended interviews defined geographic locations to street level , and it was determined that rv1 was used for multidenominational worship and therefore was recognized by different names .\nroutine contact investigation also failed to elicit other households where patients socialized ( h58 in the figure ) .\nas a result of the study , location - based contact tracing at rv1 was undertaken .\nan additional 68 persons were assessed , of which 19 ( 28% ) had latent tb ( 16 started treatment and 14 completed treatment ) and 1 had active tb .\nlatent tb was confirmed by a single interferon- release assay ; therefore , infection resulting from distant exposure could not be ruled out .\nsocial network of eritrea - born patients with tb in relation to 6 distinct 24-loci miru - vntr strain - type clusters and associated cluster members born elsewhere , united kingdom , january 2009december 2013 .\nnonclustered eritrean patients are included if > 1 epidemiologic link to clustered patients is known .\ncircles denote eritrea - born patients ; triangles denote patients born elsewhere ; solid squares denote places of social mixing . for patients ,\nlabels denote strain type cluster ( a f ; x , no strain typing available ) and chronological order of case notification within each strain type cluster . for places ,\nlabels denote type ( h , private home ; rv , religious venue ; sc , school ; wp , workplace ) .\ndouble lines with arrows denote connections between tb patients who named each other as contacts during routine contact tracing investigations .\ndetached symbols at the bottom indicate persons for whom no epidemiologic links to any other case were detected .\nmiru - vntr , mycobacterial interspersed repetitive units variable - number tandem - repeat ; tb , tuberculosis . combined strain typing and in - depth interviewing also uncovered apparent casual transmission involving cluster e at a workplace ( wp1 in the figure ) .\nsix months before diagnosis , patient e2 had worked at wp1 for 2 weeks , during the infectious period of patient e1 . as a result , 5 new workplace contacts were investigated ; 3 cases were diagnosed ( no patients were born in the united kingdom , and interferon- release assay conversion was not documented ) , and these patients completed treatment for latent tb . a third case ( in patient f5 ) occurred at wp1 , 6 months after illness of patient e2 , but the isolate from patient f5 was of a different strain type . given the low probability of transmission , no further location - based contact tracing was undertaken at wp1 .\ndiscrepant strain types between patients known to have socialized at rv2 , rv3 , and school ( sc ) 1 also suggested that these cases did not involve the same chain of transmission .\nthe infectious period for patient b1 preceded the arrival of patient b2 in birmingham , and local transmission was thought to be unlikely ; both patients originated from the same town in eritrea .\ngenetically homogenous strain lineages prevalent in the countries of origin may falsely cluster persons from the migrant population ( 10 ) ; in our study , no patients within cluster d could be linked despite extensive epidemiologic investigation .\nwe have demonstrated the value of identifying places of social mixing during contact investigation for recognizing such microepidemics early . this approach has been found useful in other settings ( 11,12 ) .\na recent evaluation of the tb strain typing service in the united kingdom found that strain typing did not significantly affect time to diagnosis or the median number of secondarily infected persons found per index case ( 13 ) .\nhowever , strain typing can highlight gaps in current contact investigation procedures in specific patient populations and can help focus resources on scenarios in which recent transmission is more likely . whole - genome sequencing may offer the ability to identify more recent strain evolution and transmission ( 14 ) .\nconventional epidemiologic methods should be improved to complement molecular epidemiologic methods and increase their effect on tb control .", "answer": "to determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in birmingham , uk , during 20042013 , we conducted enhanced epidemiologic investigation of molecular clusters . \n this technique identified exact locations of social mixing and chains of apparent recent transmission , which can be helpful for directing resources .", "id": 112} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe first and second vertebrae ( atlas and axis , respectively ) are different from others with their function and anatomy .\nnormally , the intervertebral disc is located between two vertebrae , but not located between atlas and axis .\nthe most common cervical vertebrae anomalies ( cvas ) are fusion and posterior arch deficiency ( pad ) .\nthe second ( c2 ) and third ( c3 ) cervical vertebrae are most commonly influenced by fusion .\nposterior arch anomalies occur probably the result of a locally decreased blood supply during fetal development .\nskeletal deviations in maxillofacial region , head and neck posture deformities , cervical inclination , and orthopedic findings can be associated with malocclusion .\nseveral studies declared the relation between the cervical vertebrae morphology and position of the mandible .\ncva is often asymptomatic , for this reason , patients may notice anomalies with decrease age or an injury\nthe pathologic condition may reveal with the radiographic examination . although orthodontists do not have to be experts in cva\nthese patients should be directed to the experts early as possible and prevents progressively degenerative neurologic defects .\nthe present study is the first report to determine the frequency of cvas in orthodontic patients with dental malocclusions .\nthe aims of this study were to investigate the distribution of cvas among angle class i , ii , and iii malocclusions in a turkish patient population and whether a correlation between cva and dental malocclusion ; thus , being the first series of cvas in our population described in the english literature .\na power analysis conducted using the g*power version 3.1.7 . software ( franz faul , universitt kiel , germany ) indicated that a total sample size of 150 patients would give more than 80% power ( actual power = 0.8229 ) to detect significant differences with an effect size of 0.30 at an = 0.05 level of significance ( critical = 11.0705 ; noncentrality parameter = 13.5000 ) .\nthe study was performed on 318 patients clinical records ( case histories , lateral cephalometric radiographs , and study models ) which were taken in archive at the department of orthodontics , faculty of dentistry , kirikkale university .\nif an accurate diagnosis of the cva could not be made from these records , the subject was excluded from the study .\nexclusion criteria included the patients , who were less than 18 years of age , had records with poor quality radiographs , had craniofacial anomaly and systemic muscle or joint disorder and , wound , burns , or scarring in the head and neck .\nsubjects were selected according to the following criteria : turkish with turkish grandparents , no history of trauma , and previous orthodontic treatment , study models including the first molars and standardized lateral cephalometric radiographs with the first five cervical vertebrae visible .\na total of 341 subjects were included in the study , but 23 subjects with developmental anomalies were excluded .\nthe radiographs of the patients were obtained with the teeth in occlusion , the lips in a relaxed position in a standardized head posture ( the frankfort plane parallel to the horizontal ) .\nthe radiographs were taken by an experienced x - ray technician using an orthopantograph ( planmeca proline cc 2002 , helsinki , finland ) with a film - to - focus distance of 165 cm and a film - to - median plane distance of 15 cm .\ndental malocclusion groups observed through molar relationship in plaster models were divided into angle class i , ii , and iii according to angle 's classification .\nangle class i : normal relationship of the molars ( mesiobuccal cusp of the upper molar occludes in buccal groove of the lower molar ) , but a line of occlusion incorrect because of malposed teeth , rotation , or other causes .\nangle class ii : lower molar distally positioned relative to upper molar , a line of occlusion not specified .\nangle class iii : lower molar mesially positioned relative to upper molar , a line of occlusion not specified .\ncvas were categorized and recorded for all patients : fusion was defined as no intradiscal radiolucency or osseous continuities without complete separation between two cervical vertebrae .\npad was defined as a uniform radio - opacity without an internal cortical outline at the posterior arch of the cervical vertebra .\nthe lateral cephalograms were examined by an orthodontist ( h.k . ) and a dentomaxillofacial radiologist ( e.y . ) simultaneously . to determine errors in the methods ,\n20% of the subjects with or without cva were selected randomly.first , each radiograph was separately evaluated by authors , but a final examination was done together , so a sentence was made to decide .\nin addition , the same examiners twice reevaluated all of the radiographs after 4 weeks of the first evaluation .\na paired t - test was applied to both the first set and a second set of measurements , and no significant difference was found between the two sets .\nintra - examiner reproducibility was found to be 90 and 92% , respectively , and the agreement between both investigators was 95% .\nthe chi - square and fisher 's exact test were used to determine the potential differences in the distribution of dental malocclusions , and genders when stratified by cvas .\npearson 's correlation test was used to determine the correlation between cvas and different parameters ( dental malocclusions and genders ) .\nall of the statistical analyzes were performed with the spss software package ( spss version 16.0 , spss inc .\n, 233 south wacker drive , 11 floor , chicago , il , usa ) . a p < 0.05 was considered statistically significant .\nthe final sample of 318 patients was examined ( 170 females and 148 males , mean age ; 20 0.9 years from 18 and 29 years ) . of these 318 patients , 98 ( 30.81% )\nhad angle class i , 124 ( 38.99% ) had angle class ii , and 96 ( 30.18% ) had angle class iii malocclusion .\ncva was observed in 42 individuals ( of which 26 [ 8.1% ] had fusion and 16 [ 5.0% ] had pad ) , with a frequency of 13.2% .\nof the 26 fusion defect , 8 ( 30.8% ) had angle class i , 8 ( 30.8% ) had angle class ii , and 10 ( 38.4% ) had angle class iii malocclusion .\nof the 16 pad , 8 ( 50% ) had angle class i , 8 ( 50% ) had angle class ii but no patients with angle class iii malocclusion was observed .\nthe distribution of dental malocclusions regarding cvas was not statistically significant ( p = 0.076 ) [ table 1 ] .\nthe distribution of cvas according to dental malocclusions of these 42 individuals with cva , 52.3% ( 15 fusions and 7 pad ) were females and 47.7% ( 11 fusions and 9 pad ) were males .\nthe cvas and the gender were also compared [ table 2 ] and no statistically significant differences were found ( p = 0.339 ) . as shown in table 3 , statistically significant negative correlation ( p = 0.025 )\nwas found among cvas and dental malocclusions , but no statistically significant correlation was found between cvas and genders .\naccording to the sample size calculation for a power of 0.80 at = 0.05 significant level , 150 subjects would be sufficient . at baseline\n, there were 341 subjects for this study group ; twenty - three subjects in the study group have been excluded from the study . at the end of the study , there were 318 patients for the study group .\ncorrelation between cva and vertebrae morphology , craniofacial malformations , and skeletal malocclusions were reported in the previous studies .\nthe aims of our study were to identify the prevalence of cva in turkish population and also whether there is a correlation between cva and dental malocclusion . in our study ,\nthe prevalence of fusion and pad were found 8.1% and 5.0% , respectively [ table 1 ] . besides , a statistically significant correlation ( p = 0.025 ) was found among cva and dental malocclusions [ table 3 ] .\nthe prevalence of cva was reported with a wide range of 0 - 61.4% in the literature .\nsonnesen and kjaer reported that the incidence of fusion ( 61.4% ) more common in skeletal class iii patients and skeletal horizontal overjet when compared with control group ( 14.3% ) .\nthey revealed that if a skeletal horizontal overjet was caused by maxillary retrognathia , the decreased prevalence of fusion more likely seen .\nreported that the descending distribution of cva were determined in skeletal class i , ii , and iii malocclusion , respectively ( 17 ) .\nin addition , a higher prevalence of c1 level partial cleft and occipitalization was reported in their study .\nour study was designed to investigate dental malocclusion , but the previous studies were planned to examine skeletal anomalies . to the best of our knowledge , this is the first study evaluate the frequency and distribution of cvas in orthodontic patients with dental malocclusions .\nhad stated that the angle of the cranial base and the head posture deviations were sexually dimorphic , females showing larger cervicohorizontal , and cranial base angles than males .\nin addition , they reported that the relation between the cervical column fusion and cranial base angle , the inclination of the upper cervical spine and cervical lordosis were determined in females .\nhence , it could be hypothesized that cervical column fusion has a dimorphic pattern in their occurrence .\nin contrast , some researchers affirmed that there was no significant relation between gender and the occurrence of cva in their studies .\nso that , our findings supports the studies showing no gender dimorphism [ table 2 ] .\nit is not clear why vertebral anomalies occur and why these anomalies occur in different craniofacial morphology groups and skeletal malocclusion traits .\nthe genetic studies and insight of the early embryogenesis might be essential to understand the etiology of the cva . the recent studies affirmed that the notochord may be responsible to these anomalies . because the vertebral bodies were formed around the notochord in the prenatal period .\nbesides , the jaws develop from the migration of the neural crest cells to the craniofacial area before the notochord is surrounded by bone tissue . however , the association between the precise signaling of notochord to the neural crest and the migration of the neural crest cells to the craniofacial area is still unknown .\nlateral cephalograms are usually used in orthodontic clinics to planning pretreatment and examined the postorthodontic treatment results .\nearly diagnose of these pathologies on cephalograms can provide essential documentation to the patient due to symptoms , injury , aging , and progression of the degenerative process\n. however , two - dimensional radiographs may not be valid in the diagnosis of cva , because of the superimposition of the spine inclination and radiographic overlapping of the facets .\nfor this reason , the suspectable sign of cva on cephalogram is reevaluated with three - dimensional imaging systems like cone beam computed tomography to prevent misdiagnose .\n\n the prevalence of fusion and pad were found 8.1% and 5.0% in turkish population , respectivelystatistically significant differences were found among the dental malocclusions , and no statistically significant correlation between cva and angle class i , ii , and iii malocclusionno statistically significant differences were also found between the genders , and no statistically significant correlation between cva and genders were found . \n the prevalence of fusion and pad were found 8.1% and 5.0% in turkish population , respectively statistically significant differences were found among the dental malocclusions , and no statistically significant correlation between cva and angle class i , ii , and iii malocclusion no statistically significant differences were also found between the genders , and no statistically significant correlation between cva and genders were found .", "answer": "aims : the aims of our study were to investigate the distribution of cervical vertebrae anomalies ( cvas ) among dental angle class i , ii , and iii malocclusions in turkish population and whether a correlation between cva and dental malocclusion.materials and methods : the study was performed on lateral cephalometric radiographs which were taken at the department of orthodontics , faculty of dentistry , kirikkale university . \n the final sample of 318 orthodontic patients was included in the study . \n dental malocclusions were performed according to angle classification . \n cvas were categorized : ( 1 ) fusion and ( 2 ) posterior arch deficiency ( pad ) . \n the chi - square test was used to the analysis of the potential differences among dental malocclusions.results:the final sample of 318 patients was examined . \n cva was observed in 42 individuals ( of 26 [ 8.17% ] had fusion and 16 [ 5.03% ] had pad ) , with a frequency of 13.2% . \n of the 26 fusion defect , 8 ( 30.7% ) had angle class i , 8 ( 30.7% ) had angle class ii , and 10 ( 38.4% ) had angle class iii malocclusion . \n of the 16 pad , 8 ( 50% ) had angle class i , 8 ( 50% ) had angle class ii but no patients with angle class iii malocclusion was observed . \n the distribution of dental malocclusions regarding cva was not statistically significant ( p = 0.076 ) . \n of these 42 individuals with cva , 52.3% ( 15 fusions and 7 pad ) were females and 47.7% ( 11 fusions and 9 pad ) were males.conclusion:in our study , the prevalence of fusion and pad were found 8.1% and 5.0% in turkish population , respectively . besides , no statistically significant correlation between cva and angle class i , ii , and iii malocclusions were found . \n our findings support the studies showing no gender dimorphism .", "id": 113} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsubstantial improvement in survival of people living with hiv has been observed with the introduction of antiretroviral therapy ( art ) in sub - saharan africa .\nhowever , the introduction of art has led to new immune - mediated complications from dysfunction of the recovering immune system , termed immune reconstitution inflammatory syndrome ( iris ) . in patients with cryptococcal meningitis ( cm ) , a very common opportunistic infection in sub - saharan africa ,\niris is a frequent complication that is most often associated with exaggerated inflammatory responses in the central nervous system .\nalthough cm remains the most common cause of adult meningitis in the overall population in sub - saharan africa , there are only a few recognized , reported cases of gastrointestinal ( gi ) involvement with cryptococcus in the literature .\nan hiv - infected patient on art with a history of recent cm presented with chronic abdominal pain , thickened ileum , and abdominal lymphadenopathy .\nhe was initially treated for abdominal tuberculosis ( tb ) but later , he was shown to have a histologically confirmed cryptococcoma in the ileum . the major objective of this case report is to highlight the challenges in diagnosis and management of intra - abdominal cryptococcosis , especially in the setting of recent initiation of art .\na 37 year old hiv - positive male was initially diagnosed and treated for cm in may of 2009 with amphotericin induction therapy for 2 weeks followed by fluconazole 400 mg / day .\nhe had a protracted hospital course lasting 4 weeks because of persistently high intracranial hypertension despite sterilization of his cerebrospinal fluid , and he , required repeated therapeutic lumber punctures .\nhe started art ( zidovudine , lamivudine , and efavirenz ) on the 11th june 2009 with a baseline cd4 count of 5 cells/l . at day + 21 of art\n, he reported abdominal pain with hypogastric tenderness that was empirically treated as urinary tract infection with a 5 day course of ciprofloxacin , and he noted some improvement . his cd4 count at the time had risen to 29 cells/l . at day + 35 of art ,\nhis general exam was unremarkable , except for a tachypnea of 28 breaths per minute .\nthe patient was managed as a possible atypical pneumonia with doxycycline , and his respiratory symptoms improved . however , the abdominal pain persisted intermittently with occasional vomiting . at day + 84 of art and in view of the persistent abdominal pain and an occasional dry cough ,\nanother chest radiograph was performed to exclude tb , which was also unremarkable . at this time ,\nhis cd4 was only 14 cells/l , and the hiv-1 viral load was 22,000 copies / ml . he reported 100% adherence to his art , and pill counts verified his adherence . at day + 112 of art , the patient still had similar complaints of abdominal pain and occasional vomiting .\nrepeat cd4 was 8 cells/l , and the viral load was minimally decreased at 15,475 copies / ml . the patient initially declined an ultrasound - guided biopsy but consented to the procedure at day + 140 of art .\nthis second ultrasound revealed a thickened ileum up to 6 mm , with adjacent 1 cm lymph nodes .\ntwo biopsy specimens from the lymph nodes demonstrated no abnormality at histology . at day + 168 , the patient still had the same complaints with almost unchanged cd4 of 24 cells/l and viral load of 23,755 copies / ml .\nhe was presumed to be failing art , possibly due to poor absorptive surface because of the thickened gut wall .\na decision was made to initiate empiric anti - tb treatment for possible gastrointestinal tb .\nafter one week of tb empiric therapy , the patient presented with an acute abdomen , having signs of focal peritonitis in the right iliac fossa .\nan upright abdominal radiograph demonstrated evidence of perforation with free air visible under the right hemidiaphram .\nan emergency laparotomy was performed , revealing fecal matter with purulent fluid , adhesions , pneumoperitonium , and intestinal perforation at 10 cm proximal to the ileocecal junction .\nthe confirmatory histopathology report received 2 weeks later revealed a cryptococcoma in the ileal wall as the cause of the perforation with exuberant inflammation demonstrated by the multinucleated giant cell ( figs . 2 and 3 on hematoxylin and eosin stain and figs . 4 and 5 on periodic acid - schiff stain ) .\nthe patient 's marked clinical improvement after surgery , the lack of any evidence of cryptococcal infection elsewhere in the body especially in the central nervous system and a well formed granuloma formed the basis for the patient 's continuation with maintenance dose of fluconazole 200 mg / day under observation .\nat this point , his tb medications were stopped and he was switched to second line art with subsequent viral suppression . through december 2014 , he continues to remain in care on second line art without any complaints .\nwe have presented a 37 year old hiv positive male , with a history of recent cm who subsequently developed chronic abdominal pain , eventually manifesting as a cryptococcoma of the ileum .\nafter treatment for cm and initiating art , he had presented with chronic abdominal pain and low grade fever without diarrhea .\nhe subsequently developed an intestinal perforation and presented with an acute surgical abdomen requiring bowel resection .\nwe suspected an iris phenomena , in accordance with the patient presentation shortly after initiation of art , recent history of cm , and exuberant inflammation in the granuloma on histology .\nalthough , the initial immune recovery coupled with falling hiv-1 viral loads is consistent with iris , the subsequent virological failure makes the diagnosis of paradoxical iris less clear . in cryptococcosis ,\nideally , intra - operative cultures would have been performed which could have helped distinguish iris from cryptococcal relapse , based on culture sterility vs. growth , respectively .\ncryptococcus organisms can be acquired in the gut primarily through hematogenous dissemination or less commonly through direct inoculation during paracentesis or via a neurosurgical shunt .\nthe presentation in these gi cases of cryptococcal infection is usually vague , as seen in our patient , with subacute fevers , constitutional symptoms , asthenia , and anorexia .\nvirtually every intra - abdominal organ has been reported to be affected by cryptococcal infection .\nthe diagnosis of gi cryptococcosis requires a high index of suspicion , yet as in this case , clinicians may often initially focus on other common etiologies in immunocompromised persons , such as tb .\nalthough abdominal tb was found to be the most common diagnosis in patients with hiv / aids presenting with chronic abdominal pain and abdominal lymphadenopathy , these studies were conducted predominantly in persons without cryptococcosis . among persons with a known pre - existing opportunistic infection , such as cm , the pre - test probability changes as paradoxical iris enters into the differential diagnosis . in our case ,\nthe characteristics of granulomas found in hiv - infected persons varies depending on whether or not they are receiving art . in pulmonary cryptococcomas ,\npersons not receiving art demonstrate yeast proliferation with a histiocytic response but only minor lymphocytic and neutrophilic components .\nconversely , cryptococcal granulomas in persons on art are characterized by the presence of cd4 t cells , greater response of histiocytes , and multinucleated giant - cell formation , as demonstrated in our patient .\nthere is a paucity of evidenced - based data for the management of cryptococcomas . in our case ,\nthe initial abdominal lymph node biopsy ( 5 weeks prior to the perforation ) did not reveal a diagnosis .\nthe question raised is , if we had confirmed the diagnosis of gi cryptococcoma before the perforation , would we have been able to effectively intervene . to answer this question\n, it might be important to know if the cryptococcoma were due to iris or cryptococcal relapse .\ncould the patient have benefited from immunosuppressive therapy to treat iris and perhaps , avoid the perforation , or would more enhanced fungal therapy be needed to eradicate the cryptococcus ?\ntwo case reports have described cryptococcomas due to paradoxical iris ; one in the brain and the other in the retroperitoneal abdomen . in both cases\n, they simply observed the patients but also emphasized the importance of confirming sterility of contents in the cryptococcoma by culture . in a case report by katchanov et al .\n, a similar presentation of a central nervous system cryptococcoma was initially treated with antifungals exclusively with radiological worsening until steroids were added to direct therapy at paradoxical iris .\nwe have previously reported the challenges and dangers of using corticosteroids for cm because they may be contraindicated in cases of fluconazole - resistant cryptococcal relapse .\nsurgery , corticosteroids , and interferon - gamma have been tried in iris - like cryptococcomas due cryptococcus gattii \n .\nempiric tb therapy , including rifampin , could have induced the metabolism of fluconazole , possibly lowering plasma levels by ~50% . these lower levels may have removed the fungistatic control of the cryptococcus , precipitating the perforation . however , after the surgery , the patient was observed on secondary prophylaxis doses of fluconazole , and he did well . to treat a cryptococcoma in the setting of recent initiation of art , where iris versus relapse can not be determined due to the absence of culture results , treatment with a combination of enhanced antifungal therapy and anti - inflammatory therapy\ngi cryptococcosis has been described as a rare occurrence , with only a few published case reports .\nwe have discussed an hiv - infected patient with profound immunosuppression and recent cm who developed a gi cryptococcoma during initial immune recovery followed by virological failure after initiation of art .\nthe cryptococcoma was not identified and he developed perforation of the ileum , requiring surgery . we anticipate that with the roll out of art in sub - sahara africa , we are bound to see rare presentations of some of common conditions such as cm .\nwe recommend that health workers have a high index of suspicion for unusual complications of opportunistic infections in the setting of art - associated iris .\noften treatment of iris requires only observation or anti - inflammatory drugs , but the presence of active infection needs to be excluded .\nthe authors declared no potential conflicts of interest with respect to the research , authorship , and/or publication of this article .", "answer": "the introduction of antiretroviral therapy ( art ) may lead to unusual paradoxical and unmasking presentations of opportunistic infections . \n intra - abdominal cryptococcosis is a rare manifestation of cryptococcus . \n we present the case of an hiv - infected patient on art , with a history of cryptococcal meningitis who presented with subacute , worsening abdominal pain during immune recovery . \n this evolved into chronic abdominal pain , with thickened bowel , and abdominal lymphadenopathy , while receiving empiric tuberculosis treatment . at 6-months , he developed intestinal perforation due to a histologically confirmed cryptococcoma .", "id": 114} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nleft ventricular thrombus ( lvt ) is one of the most common complications of myocardial infarction ( mi ) .\nthe incidence of lvt in patients with acute anterior mis in the prethrombolytic era is ranged from 20% to 40% and with a non anterior acute myocardial infarction ( ami ) and the risk of lvt was < 5% . although controversial , in the contemporary era of routine early revascularization and more aggressive anticoagulation , the incidence of lvt complicating as an anterior ami is likely reduced and is currently estimated at 5 - 15% .\nthe risk factors for the development of lvt are consistently irrespective of infarct treatment and include large infarct size , severe apical akinesia , or dyskinesia left ventricular ( lv ) aneurysm , and anterior mi . two - dimensional transthoracic echocardiography is the imaging modality used most often for assessing the presence , shape , and size of an lv mural thrombus with an excellent specificity of 85 - 90% and sensitivity of 95% .\nhere , we report a case of 40-year - old male patient who is presented in emergency department with the complaint of substernal chest pain radiating to left arm and back associated with sweating for the last 1 day , there was no history of dyspnea , palpitation , any limb weakness , or any history suggestive of transient ischemic attack and peripheral embolization .\nhis 12-lead electrocardiogram was suggestive of inferior wall mi [ figure 1 ] . his total leukocyte and eosinophil counts were normal , prothrombin time / international normalized ratio and activated partial thromboplastin time were normal , and other tests for hypercoagulable states were planned for the follow - up evaluation .\na transthoracic echocardiogram was performed bedside which revealed hypokinesia of basal , mid inferior , and inferoseptal wall [ figure 2 and video 1 ] .\nsurprisingly , it also revealed a mobile mass which is the most probably thrombus attached to hypokinetic inferobasal septum just near the lv outflow tract ( lvot ) [ figure 3 and video 2 ] . considering the possibility\nthat this mass was high risk for embolism , we planned for coronary angiogram followed by the surgical extraction of possible thrombus .\nhowever , unfortunately , despite the proper counseling and explanation of the risk of embolism , the patient refused for further intervention and got discharged against medical advice .\nsmall arrows showing hypokinesia of basal inferior septum , large arrow indicates left ventricle probable thrombus apical four chambers view \nthrombi formation at basal interventricular septum near lvot is extremely rare as it is a region of high - velocity blood flow .\ntraditionally , the causes of lvt formation after acute st - segment elevation mi include segmental dysfunction of the infracted myocardium resulting in the stasis of blood , endocardial tissue inflammation that provides a thrombogenic surface and a hypercoagulable state .\nthe higher mortality has been reported in patients with lv thrombi after infarction , especially when these develop within the first 48 h after infarction .\nthe treatment for cardiac mass is a prompt surgical resection of the mass with the patients placed on cardiopulmonary bypass .\ntherefore , better understanding of the circumstances in which lv thrombosis occurs may influence the patient management . in our case ,\nthrombus formed at the very unusual site and could lead to dreaded complication for the patient .\nthe possible etiology of thrombus formation , in our case , is hypokinesia of basal septum due to mi , but the presence of a subtle septal rupture which is not detectable on echocardiography could not be ruled out .", "answer": "left ventricular ( lv ) thrombus formation is a frequent complication in patients with acute anterior myocardial infarction ( mi ) . \n its incidence is lower with inferior wall mi . risk factors for the development of lv thrombus are consistently irrespective of infarct treatment and include large infarct size , severe apical akinesia or dyskinesia lv aneurysm , and anterior mi .", "id": 115} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nage , gender , oral hygiene practices , and smoking are among the important risk factors that can affect the initiation , progression , and severity of periodontitis . the prevalence and severity of periodontal disease is found to increase with age .\nfurthermore , lack of oral hygiene encourages plaque formation , which leads to increase in pathogenic bacteria that are associated with severe forms of periodontal disease . since time immemorial\n, tooth brushing has been considered ideal for maintaining a good oral hygiene . despite the relationship between tooth brushing and periodontal disease being unclear ; the breakthrough came in with rajala et al . reporting the disease to be more prevalent in sporadic toothbrush users than otherwise .\nadditionally , a positive association between tooth brushing and low periodontal disease prevalence has been confirmed in some studies .\nstudies suggest that the smokers are 11 times more likely than non - smokers to harbor the bacteria that cause periodontal disease and are 4 times more likely to have advanced periodontitis .\nthe sebha city is situated in south - western libya with a population of about 1,30,000 and people come from various urban areas surrounding it ; therefore , it has a heterogeneous society with a low level of health education . as per leous periodontal disease\nis one of the main problems in libya ; bleeding , dental calculus and shallow pockets is prevalent in almost all the young adults .\nit is also worth while to note that some of the 18-year - old male never clean their teeth with a toothbrush .\nthe periodontal disease data from several countries collected by using cpitn , is stored in the who global oral health data bank .\nthe sebha city belongs to the countries of the regional office for eastern mediterranean ( emro ) .\nthe oral health data for emro countries is available for the ages ; 15 years , 17 years , 15 - 19 years , 16 - 20 years , 35 - 44 years , and 65 - 44 years .\nusually , epidemiological studies are primarily concentrated on adolescents , adults , and elderly population .\nunfortunately , no information is available for the young adults ( 18 - 34 years ) .\nthe plausible reason for this lack of information comes from the fact that early studies presented results which suggested little or no periodontal destruction before the age of 30 years . taking into consideration the lack of data about periodontal disease among young adults ,\nthe present study has been designed to assess the periodontal status among the young adults of sebha city .\nthe study also assesses the relationship of the risk factors , such as age , gender , oral hygiene practices , and smoking with periodontal disease .\na cross - sectional survey was conducted among the young adults aged 18 - 34 years from sebha city , libya .\nthe city was divided into four zones , and one representative area from each zone was selected .\nal - jadeed , al - mahdia , gurda , and sukkara were the four selected areas .\nthis was carried out to obtain the prevalence of the periodontal disease so as to calculate the sample size for the main study .\nthe pilot study results revealed that the prevalence of periodontal disease was 56% in al - jadeed .\nthe sample size was determined by using the formula n = z pq / d .\nassuming that the values obtained are z = a point on normal distribution with 95% confidence , p = prevalence of periodontal disease from pilot study , q = 100-p , d = admissible error that is 10% of prevalence .\nthe survey was conducted at the primary health center ( phc ) in the selected areas .\nthe medical officer posted at the phc was responsible for enrolling the participants for the study in the respective areas .\nyoung adults who visited the phc for the 1 time and voluntarily wished to participate were recruited for the survey .\nschedules were prepared such that the examination of the participant took place on one particular day of the week for one phc center . at first\n, the participant was interviewed to collect information as per the pro - forma [ appendix 1 ] and later underwent a clinical examination .\nthe oral examination was conducted by a single , trained , and calibrated examiner who was assisted by a recording clerk .\n10% of the sample was re - examined and a kappa value of 0.8 was obtained .\nthe codes and criteria of the index were as per the who , oral health survey .\nthree indicators of periodontal status ; gingival bleeding , calculus , and pockets were assessed .\n, 10 index teeth were examined , which were ( 16 , 17 ) , 11 , ( 26 , 27 ) , ( 36 , 37 ) , 31 , and ( 46 , 47 ) .\nwhen two index teeth were considered in a sextant , the tooth with the highest score was recorded . for those below 20 years\n, only 6 index teeth were examined , which were 16 , 11 , 26 , 36 , 31 , and 46 .\nthe overall cpi score of the participant represented the value of the highest recorded code for that individual . during examination , the probe was kept parallel to the long axis of the tooth , the tip was inserted gently into the gingival sulcus or pocket , and the total extent of sulcus or pocket was explored .\nthe codes were : \n code 0 : teeth are healthycode 1 : bleeding observed , directly or by using a mouth mirror , after probingcode 2 : calculus detected during probing , all the black band on the probe is visiblecode 3 : pocket is 4 - 5 mm ( gingival margin within the black band on the probe)code 4 : pocket is 6 mm or more ( black band on the probe not visible)x : sextant is excluded ( less than 2 teeth present)9 : not recorded . \n \ncode 0 : teeth are healthy code 1 : bleeding observed , directly or by using a mouth mirror , after probing code 2 : calculus detected during probing , all the black band on the probe is visible code 3 : pocket is 4 - 5 mm ( gingival margin within the black band on the probe ) code 4 : pocket is 6 mm or more ( black band on the probe not visible ) x : sextant is excluded ( less than 2 teeth present ) all the subjects were well - educated and signed the informed consent form . the ethical board , scientific committee of the faculty of dentistry , sebha university , sebha , libya approved the protocol of the study .\nstatistical analysis was carried out with the help of a statistical package for social sciences ( spss version 16 ) .\nchi - square test and analysis of variance ( anova ) was used to compare between the groups at 5% level of significance .\nthe variables were age , gender , frequency of tooth brushing , and smoking habit that were compared with the cpi codes .\nout of the determined sample size of 1,256 people , the study population comprised of 1,255 individuals , of which 1,006 ( 80.15% ) were females and 249 ( 19.84% ) were males .\nthe distribution of the sample as per the age and age groups is shown in table 1 .\ndistribution of the study sample according to the age regarding the oral hygiene practices , overall , 1,118 ( 89.08% ) people reported to have used toothbrush and toothpaste for cleaning and 137 ( 10.91% ) people used other aids , such as finger and siwak . only 50 ( 3.98% ) people were current smokers and all were males , of which maximum ( n = 22 ) people smoked 10 - 20 cigarettes / day .\noverall , the cpi analysis showed that a majority of 44.30% ( n = 556 ) were detected with calculus ( cpi code 2 ) followed by 40.63% ( n = 510 ) with shallow pockets ( cpi code 3 ) , 6.29% ( n = 79 ) with bleeding ( cpi code 1 ) , and 4.06% ( n = 51 ) with deep pockets ( cpi code 4 ) .\nonly 4.7% ( n = 59 ) had healthy periodontium ( cpi code 0 ) .\ntable 2 shows the distribution of people according to the cpi codes in relation to the different variables considered in the study .\nthe frequency of tooth brushing and smoking were not significantly related to the cpi codes .\ndistribution of people according to the community periodontal index cpi codes in relation to the different variables the overall mean cpi score was 2.33 ( 0.84 ) .\nmean cpi score of the sample for different ages table 3 shows the mean ( sd ) number of sextants as per the cpi codes in relation to age .\na maximum of 2.45 sextants were healthy among 18 years old , which further gradually decreased as the age advanced . from 19 years onward\nmean ( sd ) number of sextants as per the cpi codes in relation to age\nthe literature search for information regarding the oral health status of the population in sebha resulted in the presence of only one pubmed indexed article by hassan and one document that was an assignment report on the oral health situation in socialist people 's libiyan arab jamahiriya submitted to who geneva by leous .\nthe study by hassan among patients attending the dental clinic in sebha , libyan arab jamahiriya , reported that the people here , have poor oral hygiene and low level of education .\nfurthermore , it was found that caries ( 54% ) and periodontal disease ( 41% ) were the main causes for the high frequency of tooth extraction .\nthe report by leous was a pathfinder study conducted on 849 children and 269 adults from 14 sites of the following localities : tripoli , sebha , benghazi , zwara , ajelat , and kaddah .\nthe cpitn index was used to assess the periodontal disease , and its results indicate that the periodontal disease was present from a very young age .\nvery small population in the age group of 20 - 24 years was found to have a healthy periodontium . while drawing a comparison between the population aged 18 years and 20 - 24 years , respective percentage distributions\nwere observed : 3% and 2% had healthy periodontium , 8% and 0% had bleeding , 66% and 69% had calculus , 25% and 27% had shallow pockets , and 0% and 2% had deep pockets . comparing results of the present study with the results reported by leous indicate the percentages of people with cpi code 0 , 1 , 3 , and 4 to be different , while the prevalence of calculus ( code 2 ) was found to be the highest in both the studies . in the who global oral health data bank for periodontal disease using cpitn index , there was no data available for comparison in the age group 18 - 34 years from emro countries . however , for the ages 18 and 19 years , data from countries belonging to regional office for europe ( euro ) , regional office for western pacific ( wpro ) , regional office for africa ( afro ) , and regional office for south east asia ( searo ) was available and was compared with the present study participants of the same age [ figure 2 ] .\nfigure 2 presents a view for all the countries , calculus ( code 2 ) was the highest - recorded cpi score except in south africa where the percentage of healthy periodontium was the highest ( 51% ) .\noverall , it was observed that the highest prevalence of shallow pockets ( 34% ) was from sebha .\noverview of periodontal status from different countries it is widely assumed that symptoms of periodontal diseases escalate with age .\ntable 3 clearly indicates that the mean number of sextants for lower codes of 0 ( healthy ) and 1 ( bleeding ) was highest among 18 years old , but as the age increased , the mean number of sextants for higher codes of 2 ( calculus ) and 3 ( shallow pockets ) increased .\nthe presence of shallow pockets , which is an indication of the deterioration of periodontium , was more prevalent in the age group of 25 and above . in the present study\n, a significant relation was obtained between cpi codes and gender [ table 2 ] .\nalthough , there was an unequal distribution of males and females , the individual percentage calculation showed that more females had healthy periodontium , bleeding , and calculus as compared to males .\nhowever , the prevalence of shallow and deep pocket was more prevalent in the males .\nstudies indicate that predominantly males , because of their smoking habit , have shown more susceptibility to periodontal diseases .\nthough , the smokers in the present study were all males , significant difference in periodontal status was not observed with smoking .\nthis is a good percentage when compared to other previous studies on libyan and sudanese population , where the percentages were 74.6% and 53% , respectively .\ncurrently , many of the world populations in india , pakistan , several african countries , the arab countries , and most of the muslim world still use miswak .\nthe study reported that the sudanese regular miswak users had better oral health and lower levels of oral pathogens than adult sudanese who used a modern toothbrush regularly .\nhowever , in the present study , the frequency of tooth brushing was not significantly associated with the cpi codes .\nwithin the limits of the study , it can be concluded that only 4.7% young adults in sebha have healthy periodontium .\nthe benefits accuring from the control of periodontal diseases and promoting good periodontal health include , improved quality of life , enhanced general well - being and appearance , reduced halitosis , elimination of bleeding gums , reduced potential threat to longevity of teeth , and improved masticatory function .\nmore importantly , ensuring implementation of preventive procedures amongst young adults could possibly lessen the prevalence of periodontal diseases during their adulthood .\nthis study is probably , the first of its kind to report data on the young adults in sebha and this information can be utilized for planning a preventive model that will include dental health education and preventive procedures .", "answer": "background : the occurrence of periodontal diseases in humans has been a global problem . \n certain risk factors affect the initiation , progression , and severity of periodontitis . \n the present study has been designed to assess the periodontal status in relation to risk factors such as age , gender , oral hygiene practices , and smoking among the young adults of the sebha city in libya.materials and methods : a cross - sectional study was carried out among 1,255 subjects aged between 18 years and 34 years . \n 1,006 ( 80.15% ) subjects were females and 249 ( 19.84% ) subjects were males . \n data was generated by conducting interview and clinical examination . \n the periodontal status was assessed by using community periodontal index of community periodontal index of treatment needs . \n the chi - square test and analysis of variance were used for statistical analysis at 5% level of significance.results:a total of 89.08% reported the use of toothbrush and toothpaste for cleaning and 10.91% used other aids , such as finger and siwak . \n of the 1,255 subjects , 3.98% were current smokers ( all males ) . \n only 4.7% had healthy periodontium ( cpi code 1 ) , while majority of 44.30% were detected with calculus ( cpi code 2 ) . \n nearly 40.63% had shallow pockets ( cpi code 3 ) , 6.29% had bleeding ( cpi code 1 ) , and 4.06% had deep pockets ( cpi code 4 ) . \n the overall mean cpi score was 2.33 ( 0.84 ) . \n age and gender showed a statistically significant difference with the cpi codes.conclusion:the result of this study provides baseline information for planning a preventive program . with preventive procedures \n being implemented at this young age , there is a possibility that the prevalence of periodontal disease will be lesser during adulthood .", "id": 116} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsonographic estimation of fetal weight ( fw ) , especially in late pregnancy is an important guide in obstetric care .\narmed with this information informed decisions about delivery can be taken , thereby minimizing perinatal morbidity and mortality .\namniotic fluid cushions the fetus from traumatic forces , cord compression , and pathogens , as well as playing an essential role in fetal lung development . in late pregnancy\n, amniotic fluid production is largely dependent on fetal micturition and renal size in the newborn has been shown to bear a significant relationship to birth weight .\nit is therefore , reasonable to postulate a relationship between sonographically determined amniotic fluid index ( afi ) and estimated fw .\nprevious reports have investigated possible relationships between sonographically attained fluid index , and estimated fetal weight ( efw ) including the influence of afi on the accuracy of sonographically efw , among caucasians . however , such studies are rare among africans , especially nigerians .\nthis study was carried out to find out if any significant relationships exist between afi and efw in a nigerian cohort of healthy pregnant women .\ntwo hundred and fifty - eight low - risk pregnant subjects referred for routine ultrasound scans to the radiology department of the university of benin teaching hospital , nigeria were randomly selected over a 12-month period .\nthose with unsure dates , diabetes mellitus , and hypertensive disorders were excluded . only those whose menstrual dates\nsonography was performed with a 3.5 mhz transducer ( fukuda denshi ; fukuda co ltd , japan ) .\nfetal biometrics including biparietal diameter ( bpd ) , using the cavum septum pellucidum as landmark , as depicted in figure 1 ; fetal trunk cross sectional area ( fta ) using the four chamber view of the heart , as illustrated in figure 2 ; and the femur length ( fl ) , with the hook from the greater trochanter to the distal metaphysis included , as illustrated in figure 3 , were measured .\nthe fw was automatically estimated by the scanner using a combination of the bpd , fta , and fl , based on the in - built osaka university system 's formula .\nultrasound scan shows how to measure fetal trunk cross sectional area , using the four chamber view of the heart .\nsample report 1 shows estimated fetal weight calculated by the osaka university system 's formula .\nsample report 2 shows estimated fetal weight calculated by the osaka university system 's formula .\ndata was entered into a microsoft spreadsheet and analysed using the statistical package for the social sciences ( spss version 16 ) .\nmeasurements were stratified into pairs of afi and efw as follows ; 27 - 29 weeks , 30 - 32 weeks , 33 - 35 weeks , 36 - 38 weeks , and 39 - 41 weeks .\nspearman 's correlation was used to test possible relationship between the afi and efw pairs .\nthe mean age of the subjects was 29.1 4.9 years , and parity ranged from 0 to 7 , with a mean of 1.5 .\nthe mean maternal weight was 71.4 13.6 kg , and height was 1.6 0.5 m. the number of subjects in each gestational group were distributed as follows ; 64 ( 24.8% ) in the 27 - 29 weeks , 56 ( 21.7% ) in the 30 - 32 weeks ; 48 ( 18.6% ) in the 33 - 35 weeks ; 50 ( 19.4% ) in the 36 - 38 weeks , and 40 ( 15.5% ) in the 39 - 41 weeks ; as outlined in table 1 .\namniotic fluid index and estimated fetal weight values for the gestational age ranges table 1 also shows that the mean afi and efw values for 27 - 29 weeks gestation were 172.1 mm and 1250.19 g respectively ; 30 - 32 weeks were 170.3 mm and 1,648.04 g ; 33 - 35 weeks were 162.3 mm and 2,273.54 g ; 36 - 38 weeks were 144.0 mm and 2,906.12 g ; and 39 - 41 weeks were 125.0 mm and 3,222.65 g. spearman 's correlation values between afi and efw were 0.123 , 0.472 , 0.179 , 0.210 , and 0.221 for 27 - 29 weeks , 30 - 32 weeks , 33 - 35 weeks , 36 - 38 weeks , and 39 - 41 weeks respectively .\nthere was no significant association between afi and efw for all subdivisions of gestation age , except in the 30 - 32 weeks group ( p < 0.05 ; r = 0.472 ) .\noverall , there was no statistically significant relationship between afi and efw ( p > 0.05 ; r = 0.241 ) .\nfigure 6 shows the scatter plot diagram for all pairs of afi and efw , with r value of 0.241 .\namniotic fluid disorders , oligo - hydramnios , and poly - hydramnios have been associated with intrauterine growth restriction and abnormal fetal growth , but this relationship across the entire range of fws is unclear . however , when used alone , amniotic fluid measurement has been found to perform poorly in predicting fetal distress , fetal growth restriction or low apgar scores , among others .\npolyhydramnios and oligohydramnios could overestimate or underestimate sonographic fw assessment . while there are reports of afi measurements and ultrasound efws , as separate parameters , both in the nigerian and international literature,[810 ] there are few reports that assessed the possible relationship between afi and estimated weight , for both normal ( non - diabetic ) and diabetic pregnancies .\nthis study found a decrease in mean afi values from 172.1 mm in early third trimester ( 27 - 29 weeks ) , to a value of 144.0 mm at 36 - 38 weeks , before a sharp drop to 125.0 mm at 39 - 40 weeks , as observed in previous studies .\nas expected increase in fw was noticed throughout pregnancy , but there was no significant association between afi and efw when all the afi and efw pairs were considered ( p > 0.05 ; r = 0.241 ) . only the afi and efw pair for gestation age 30 - 32 weeks showed any significant relationship ; ( p < 0.05 ) .\nthis lack of significant relationship between afi and efw across all gestational age strata is supported by the works of perni et al . , and owen et al .\npossible reasons adduced for this are that swallowing and urinating mechanisms , rather than fetal size , are more involved in regulation of amniotic fluid volume .\nthe implication of this is that fetal size may not need to be considered in variations of amniotic fluid volume across the gestational ages .\nit is interesting to note that kofinas and kofinas in 2012 , found a significant relationship between afi and efw for both diabetic and non - diabetic pregnancies .\nwhile no explanation was offered for the former , it was postulated that fetuses of diabetic pregnancies spend more time breathing than swallowing ; since swallowing and breathing are mutually exclusive , the fetuses do not swallow as much amniotic fluid as expected ; thus in diabetic pregnancies , it may be necessary to consider fetal size when interpreting amniotic fluid variations across gestational ages .\nthis present report on relationship between amniotic fluid and estimated fetal weight is probably the first among pregnant women in nigeria and therefore , raises the need for more studies on the subject , especially with larger sample sizes .\nit has nonetheless supported the majority of the views of similar works in the foreign literature that reported the non - dependence of amniotic fluid measurements on ultrasound estimated fetal size .\nthis study has produced a range of values of afi and efw among nigerian africans . however , no significant relationship exists between these parameters .\nthe probable implication of this is neither parameter merits consideration when variations in the other are considered .", "answer": "introduction : fetal weight ( fw ) estimation in late pregnancy is an important guide in obstetric care . \n amniotic fluid protects the fetus against traumatic and infective insults . \n there possibly exists a relationship between fw and amniotic fluid index ( afi ) that can be estimated by ultrasonography.materials and methods : two hundred and fifty - eight low - risk pregnancies were prospectively studied by means of ultrasound over a 12-month period . \n fw was estimated using a combination of fetal parameters ; bi - parietal diameter , fetal trunk cross sectional area , and femur length . \n afi was assessed using the 4-quadrant method . \n spearman 's correlation was used to test possible relationship between amniotic fluid indices and estimated fw pairs . \n the level of statistical significance was set at p 0.05.results:the mean af1 and estimated fetal weight ( efw ) pairs were as follows : at 27 - 29 weeks the values were 172.1 mm and 1,250.2 g ; at 30 - 32 weeks af1 and efw values were 170.3 mm and 1,648.0 g ; at 33 - 35 weeks values were 162.3 mm and 2,273.5 g ; at 36 - 38 weeks values were 144.09 mm and 2,906.1 g ; at 39 - 40 weeks af1 and efw values were 125.0 mm and 3,222.6 g. overall , there was no statistically significant relationship between afi and efw ( p > 0.05 ; r = 0.241).conclusion : while fw calculations and amniotic index showed variations in value in late pregnancy , there does not appear to be a linear relationship between ultrasound estimate of fw and amniotic index . \n the implication of this is that fetal size need not be taken into cognizance when alterations in amniotic fluid values are noted .", "id": 117} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n disporopsis pernyi ( hua ) diels , which belongs to disporopsis genus of liliaceae family , mainly grows in south asia such as vietnam , laos , thailand , and yangtze river basin of china .\nit was a well - known traditional chinese medicine which has been widely used for the treatment of abnormal sweating , chronic cough , women postpartum weakness and irregular menstrual cycle , and so forth .\nthe medical value of disporopsis genus plants has not got much attention until the beginning of 21st century .\nthe roots of the plant are rich in bioactive substances which are possible to have considerable medicinal value and can be used for hypertension cough , inflammation , and tumor .\nstudy suggests that a total of 4 polyphenolic compounds are found in extract including rutin , luteolin , quercetin , and betulinic acid , and the phenolic compounds contribute significantly to the antioxidant and antimicrobial activities [ 2 , 3 ] .\nrutin has both antihypertensive effect and antidiabetes effect [ 4 , 5 ] . luteolin which has anti - inflammatory , antibiosis , and anticancer properties has been used for relieving cough and eliminating phlegm . in addition , it has potential anti - hiv effect [ 6 , 7 ] .\nquercetin can be used for relieving cough and eliminating phlegm and for hypertension and hyperlipemia ; also , it has neuroprotective and antiproliferative activities [ 8 , 9 ] .\nacid can kill human melanoma cell without hurting healthy cell and inhibit the hiv-1 infection .\nadditionally , recent study shows that it also has the inhibition effects of cerebroma and leukocythemia [ 10 , 11 ] .\nthe four compounds are major bioactive constitutes in the extract of disporopsis pernyi ( hua ) diels roots .\nso far , there is no report on the content of the 4 polyphenolic compounds in disporopsis pernyi ( hua ) diels .\nuplc is a simple and quick tool for the quantitative determination of the bioactive constituents in pharmaceutical industry [ 1214 ] . as rutin , luteolin , quercetin , and betulinic acid\nthe hplc - grade methanol and acetonitrile used were purchased from caledon ( canada ) and formic acid was obtained from dima company ( beijing , china ) .\nthe rutin , luteolin , quercetin , and betulinic acid were purchased from the national institute for the control of pharmaceutical and biological products in china .\nthe purity of the standard compounds was 98% ; their chemical structures are shown in figure 1 .\ndisporopsis pernyi ( hua ) diels were collected from songtao which is in guizhou province of china .\nstandard stock solutions of rutin , luteolin , quercetin , and betulinic acid were dissolved in methanol , at concentration of 1.0 mg / ml . all standard solutions were filtered through 0.22 m syringe filter . the extraction was carried out using 5.0 g of powdered roots . it was dissolved in 50 ml of 70% ethanol solution and back - flow for 60 min .\nafter filter and rotary evaporation to no ethanol smell , 50 ml acetic ether was added and extraction was done three times .\nthe extract and washing liquid were combined and filtered and then evaporated to dryness under reduced pressure in a rotary evaporator .\nthe dried extract was dissolved in methanol and diluted to a 5 ml volumetric flask .\nthe hplc system used was a shimadzu nexera x2 uplc ( kyoto , japan ) chromatograph equipped with a solvent delivery unit ( lc-30ad ) , an autosampler ( sil-30ac ) , a column oven ( cto-20a ) , a degasser ( dgu-20a5r ) , and a photodiode array detector ( spd - m20a ) .\nseparation was conducted on a shim - pack xr - ods column ( 2.0 75 mm , 1.6 m ; shimadzu cooperation , japan ) .\nthe column temperature was set at 30c . the mobile phase consisted of water containing 0.1% formic acid ( a ) and acetonitrile ( b ) .\nthe composition of the mobile phase was 5% ( b ) for 02 min , 5%10% ( b ) for 24.5 min , 10%40% ( b ) for 4.511 min , 40%60% ( b ) for 1113 min , 60%70% ( b ) for 13 - 14 min , 70%80% ( b ) for 1416 min , 80%90% ( b ) for 16 - 17 min , 90% ( b ) for 1720 min , and it was held for 3 min and then reequilibrated to 5% ( b ) until the end of the analysis .\nthe flow rate was 0.2 ml / min and the injection volume was 5 l .\nthe detection wavelengths of all standards and samples were in the uv at 210 , 254 , and 280 nm .\nthe 4 standard compounds were accurately weighed and dissolved in methanol to prepare stock solutions at a concentration of 1.0 mg / ml . stock solutions of the compounds were serially diluted to construct calibration curves .\nthe diluted concentrations of compounds were plotted against the peak area on the calibration curves and the linearity was measured from the correlation coefficient .\nblank samples were analyzed in triplicate and the area of the noise peak was calculated as the response .\nthe lod and loq were calculated as lod = 3.3 sd / s and loq = 10 sd / s , where sd is the standard deviation of the response and s is the slope of the calibration curve .\nthe precision was calculated by analyzing sample extracts containing low and high concentrations of the compounds .\nthe precision was represented by the relative standard deviation ( rsd ) , which was calculated using the equation rsd = ( standard deviation / mean ) 100 .\nthe precision was measured three times in a single day ( intraday precision ) and over three consecutive days ( interday precision ) .\nthe recovery was calculated as follows : recovery ( % ) = ( ( detected concentration initial concentration)/spiked concentration ) 100 .\nwe used pda detector in this experiment , which could select each wavelength of chromatogram . in our study , we took into account the question that most of the components we studied also have good absorption at wavelength of 350 nm and 370 nm [ 15 , 17 ] . by comparing the resolution and response at different wavelength , the results showed that the resolution and response of the four components at 350 nm and 370 nm are not as good as the wavelengths 210 , 254 , and 280 nm we chose . also , we chose 210 nm to detect betulinic acid for its good response .\ncombined with the literature reports , methanol - water , acetonitrile - water , and methanol - acetonitrile - water were examined as mobile phase as well as the type ( formic acid and glacial acetic acid ) and concentration ( 0.01% , 0.05% , and 0.1% ) of the acid . a shim - pack xr - ods column was employed for the simultaneous determination of the 4 compounds , as it has been the most frequently used technique in the chemical analysis of herbal medicines by uplc .\npeak resolution and shape of the compounds were considered better indicators when 0.1% formic acid was used as a modifier .\ntaking peak shape , degree of separation , the symmetrical factor , and other factors into consideration , acetonitrile-0.1% formic acid water solution was determined as gradient elution process .\nthe linearity of the calibration curve was measured by the correlation coefficient ( r ) , which ranged in value from 0.9992 to 0.9997 for each compound .\nthe lod and loq were 0.1370.264 g / ml and 0.4560.881 g / ml , respectively ( table 1 ) .\nthe intra- and interday precision , which were represented by the rsd values , were rsd < 2.0% .\nthe recoveries of the 4 compounds were in the range 96.2%102.6% , with rsd < 2.0% ( table 2 ) .\nthe results indicate that the developed analytical method was accurate and precise for the analysis of the 4 compounds in disporopsis pernyi ( hua ) diels .\nthe method we developed was applied to determine the 4 compounds in disporopsis pernyi ( hua ) diels successfully .\nthe calculated contents of the four compounds were 5.63 g / g for rutin , 2.51 g / g for luteolin , 3.87 g / g for quercetin , and 2.41 g / g for betulinic acid .\nthe uplc method mentioned here represented an excellent technique for simultaneous determination of rutin , luteolin , quercetin , and betulinic acid in the extract of disporopsis pernyi ( hua ) diels roots , with good sensitivity , precision , and reproducibility .\nthe method gives a good resolution among the four components with the analysis time ( 25 min ) .\nfurthermore , the method can be used as quality control of polyphenolic compounds in disporopsis pernyi ( hua ) diels roots and will play a reference role on the determination of polyphenolic compounds in other medicinal plants or pharmaceutical preparations .", "answer": "disporopsis pernyi ( hua ) diels , which belongs to genus disporopsis , has been widely used for the treatment of abnormal sweating , chronic cough , and so forth . \n an ultra - performance liquid chromatography ( uplc ) analysis was developed for the determination of rutin , luteolin , quercetin , and betulinic acid in disporopsis pernyi ( hua ) diels roots . \n uplc analysis was conducted by using a shim - pack xr - ods column with gradient elution with the mobile phase of acetonitrile and water containing 0.1% formic acid and with a flow rate of 0.2 ml / min , detected at 210 , 254 , and 280 nm . \n the method was precise , with relative standard deviation < 2.0% . \n the recoveries for the four components in disporopsis pernyi ( hua ) diels were between 98.5 and 100.9% . \n the average contents of rutin , luteolin , quercetin , and betulinic acid in roots were 5.63 , 2.51 , 3.87 , and 2.41 g / g , respectively . \n the method was accurate and reproducible and it can provide a quantitative basis for quality control of disporopsis pernyi ( hua ) diels .", "id": 118} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR\n\nPaper sections:\n\nNatural products have long been a source of inspiration for drug discovery, especially in the area of cancer research.1 Indeed, from the period of 1981 to 2010, 75% of all FDA-approved new chemical entities (NCE) for treatment of cancer were either derived from or inspired by natural products.1 One of the richest sources of naturally derived chemotherapies is the Madagascar periwinkle (Catharanthus roseus) which produces the cytotoxic vinca alkaloids, vinblastine and vincristine.2,3 Vindesine and vinorelbine are two semi-synthetic drugs that are built from the naturally occurring scaffolds. Also, the Madagascar periwinkle is a source of the eburnamine-vincamine alkaloids, vincamine (1) and (\u2212)-eburnamonine (2) (Fig. 1).4 These alkaloids are unique because they display their biological activity in the CNS. Another important member of this class of alkaloid is vinpocetine (3) which is a synthetic derivative of 1.4,5
Although vincamine 1 is generally considered to be the mother compound of these cerebrally active alkaloids, eburnamonine 2 has been shown to improve cerebrovascular disorders in patients.4,6 Moreover, in studies in canines, it can enhance both oxygen and glucose consumption in the brain as well as improve the brain's oxygen supply by increasing vertebral blood flow.4 Additional studies in rats have revealed that eburnamonine 2 can help alleviate learning and memory impairments in different experimental models of amnesia7 and can improve cerebrovascular function.8 Even though the mechanism of action has not been fully elucidated, it has been established that 2 has a relatively high affinity for human muscarinic receptors.9,10
Due to the array of biological activities displayed by these alkaloids, they have been a target of synthetic and medicinal chemists. For example, a total synthesis of (\u2212)-eburnamonine 2 and of (+)-epi-eburnamonine was accomplished by Wee.11 The most efficient total synthesis of racemic eburnamonine was published by Ghosh with an excellent overall yield of 35%.12 Eburnamonine (2) can also be accessed directly from vincamine (1) using a one-pot two-step procedure13 which was later optimized.14 Analogues of eburnamonine have been prepared by hydroxylation,15,16 trifluoromethylation,17 and nitration,16 but biological evaluations of these derivatives have not been reported. Amide derivatives of 2 at the C11-position have been synthesized and were investigated as protective agents against tin-induced brain edema.18 More recently, vinpocetine analogues were prepared and examined as potential antioxidants and cognitive enhancing agents.5 In 2011, Colby and co-workers synthesized 15-methylene-eburnamonine (4) by using an \u03b1-methylenation strategy that is promoted by the release of trifluoroacetate (Scheme 1).19 Analogue 4 displays antiproliferative activity in HL-60 (human leukemia) and cytotoxicity in MDA-MB-231 (breast cancer) cells (LC50 = 14.1 \u03bcM); however, the parent natural product 2 is nearly inactive in both cell lines. Even though the conversion of eburnamonine 2 into 15-methylene-eburnamonine 4 was accomplished in two steps, the yield was quite low (i.e., 28%). The steric congestion at the C16 position of 2 is apparent in its X-ray structure20 and prevents the installation of the \u03b1-methylene group using many other standard protocols; therefore the trifluoroacetate-release olefination approach was required to access the target 4. In order to conduct a more extensive biological evaluation of 4 in malignant cells as well as define its mechanism of action, an improved synthesis was clearly needed. Herein, we describe an efficient and scalable synthesis of 4 from 1 that enabled an investigation of its antiproliferative in additional cell lines and characterization of its mechanism of action by quantitative NMR.
Even though the target 4 was originally synthesized from eburnamonine 2, a more plentiful starting material was required to enable the production of larger quantities of 4; therefore, the aforementioned one-pot two-step synthesis from vincamine 1 was selected (Scheme 2).13 Accordingly, the alkaloid 1 was reduced with NaBH4 and BF3\u00b7OEt2 at 0 \u00b0C and then treated with a mixture of aqueous H2O2 and NaOH. Following purification, gram quantities of eburnamonine 2 were accessed. Next, 2 was transformed into oxime 5 (as a pair of rotamers) using t-BuOK and t-BuONO by the literature protocol.21 Acid-promoted hydrolysis with 15% aqueous HCl at 110 \u00b0C provided the known dione 6 in 64% yield (from 2).21 All of the new and previously reported compounds were characterized by 1H NMR, 13C NMR, IR, HRMS, and optical rotation.
Studies to convert the dione 6 into the target 4 were undertaken using a series of Wittig reactions that are listed in Table 1. Excess quantities of t-BuOK and PPh3CH3I were used in all of the reactions to promote this olefination process, but regardless of temperature, base, or solvent, only unreacted starting material was isolated. These results were disappointing because high temperatures can aid in the olefination of sterically hindered carbonyl groups using Wittig reactions. Next, titanium methylene complexes were screened,22 and only the highly reactive Tebbe reagent could overcome this critical issue of steric congestion at the C16 position and produce 4 in an optimized 16% yield.
A Peterson-type methylenation was then selected and trimethylsilylmethyl lithium was reacted with the ketone 6 to give the stable tertiary alcohol 7 (Scheme 3).23 Next, protodesilylation/elimination was attempted using many conditions, but this approach was not successful. For example, the alcohol 7 was completely inert to BF3\u00b7OEt2 and merely desilylated following exposure to TFA Therefore, the sterically encumbered tertiary alcohol 7 was trifluoroacetylated to 8 with TFAA and TMSOTf,24 which were required over the less-reactive, traditional mixture of TFAA with DMAP. The intermediate trifluoroacetyl ester 8 was treated with TASF to liberate the silyl group and eliminate trifluoroacetate; the target 15-methylene-eburnamonine 4 was finally accessed. The four-step sequence from the oxime 5 provides the product 4 in 59% yield.25 Although the highest yields in the final step were obtained with TASF, this reagent was replaced with CsF in DMF on a larger scale with only a modest decrease of isolated yields. The overall yield from vincamine 1 is 40%. Accordingly, we have synthesized up to 115 mg of 15-methylene-eburnamoine 4 for biological and mechanistic evaluations.
15-Methylene-eburnamonine 4 and eburnamonine 2 were tested side-by-side for cytotoxic activity in four additional cell lines: LNCaP (prostate cancer), RPMI-8226 (multiple myeloma), U266 (multiple myeloma), and KMS-12BM (multiple myeloma) cells (Table 2).26 Our rationale for choosing these additional cell lines is to compare prostate cancer cells to breast cancer cells and apply our prior discovery that enone-based anti-leukemic agents are also active against multiple myeloma cell lines.27 Agent 4 displays micromolar activity against the four cell lines and the natural product 2 is nearly inactive even at the high dose of 100 \u03bcM. Compound 4 displays higher cytotoxicity in prostate and myeloma cells compared to MDA-MB-231 (breast cancer) cells.19 Its most potent effects were LC50 = 4.3 \u03bcM (U266) and LC50 = 4.0 \u03bcM (KMS-12BM), and these low micromolar activities were an excellent validation of the aforementioned synthetic studies. The cell viability curves for four cancer cell lines are depicted in Figure 2 and present additional perspective on the side-by-side comparisons between 2 and 4. These viability curves, along with the previously published curves in MDA-MB-231 cells,19 display the repeated difference between the two agents across the five cells in that only compound 4 eliminates cancer cells in the low micromolar range. An additional antiproliferative study was conducted with agent 4 in an immortalized non-cancerous cell line to examine its potential selectivity for cancer cells. Indeed, highly selective killing of cancer cells has been demonstrated by the natural product, piperlongumine, which bears a similar \u03b1,\u03b2-unsaturated amide.28 The LC50 value of 4 in FnMSC cells, an immortalized mesenchymal stem cell line derived from the bone marrow, is 16.71 \u03bcM.29 The direct comparison of this data to cancer cells is to the LC50 value of 4.0 \u03bcM in KMS-12BM cells, and these data demonstrate decrease in potency in the non-cancerous cells compared to cancer cells.
The incorporation of an \u03b1-methylene group on eburnamonine 2 (thus forming 4) clearly imparted cytotoxic activity against the cancer cell lines. It is well known that \u03b1,\u03b2-unsaturated carbonyl groups may produce cytotoxic effects following a Michael addition from nucleophiles such as biological thiols.30 To define the structure\u2013activity relationship of the enone of 4, the \u03b1,\u03b2-unsaturation was reduced with Pd/C and H2 and analogue 9 was produced in 85% yield as a single diastereomer (Fig. 3).31 The axial assignment of the stereochemical configuration at the C15-site (eburnamonine numbering, see Fig. 1) was accomplished after acquisition of COSY and NOESY. On derivative 9, the proton at the C15 position is a quartet (J = 7.0 Hz) at 2.83 ppm and displays a NOESY crosspeak with the axial methine proton at the C3 position. This proton (see also Scheme 1) is a singlet at 4.16 ppm and exhibits a key NOESY crosspeak with the axial C21 methyl group (t, J = 7.5 Hz) at 0.98 ppm. These data support the axial assignment, because each is on the same face of the molecule. Next, a comparison of the cytotoxic effects of 9 and 4 in MDA-MB-231 cells demonstrates the expected loss of biological activity from removing the unsaturation at C15-position (Fig. 3B). These data validate the critical nature of the enone and this important structure\u2013activity relationship.
To establish the reactivity of the enone towards thiol-based nucleophiles,32 quantitative NMR studies were conducted.30,33 Quantitative NMR is a powerful analytical tool, and although the utility of NMR for structure determination is well established, its potential application in quantitation has not been fully appreciated in bio-organic and medicinal chemistry. Specifically, almost all molecules readily generate unique NMR signals, and the amplitude (integration) of NMR signals can be acquired proportional to the concentration. This technique eliminates the requirement of an internal standard to calibrate concentration. Knowing the exact concentration of a biologically active molecule and calculating the change in concentration in relationship to time provides valuable kinetic data. This point is fundamental in the reactivity of enones towards thiol-based nucleophiles, because the structure of the enone and the nature of the solvent can cause substantial differences in reactivity.32 Dithiothreitol (DTT) was chosen as a representative thiol for investigation with 15-methylene-eburanmonine 4 without any deuterated solvent.34 Accordingly, in an NMR tube, DTT (10 equiv) was added in one portion to a solution of 4 in 80% PBS buffer (pH 8.0) and 20% ethanol. The NMR sample was immediately placed in the spectrometer and spectra were acquired at intervals of 2, 8, 18, and 80 min. (Fig. 4). The 1H NMR peaks corresponding to the methylene groups disappeared after the addition of DTT; these data indicate that the thiol was adding into the enone. The changes in the concentration of 4 were simultaneously quantified by NMR at each time interval using our previously published no-D NMR methods (Fig. 4B).33,35 At t = 0 min, the concentration of 4 was 400 \u03bcM. Two minutes after treatment with DTT, the concentration of 4 decreased to 330 \u03bcM. After 18 min had elapsed, the concentration of 4 was 220 \u03bcM, and after 80 min, the compound was not detected (Fig. 4C).
These studies demonstrate the utility of installing an exocyclic enone into the structure of a natural product to impart anticancer activity as well as chemical reactivity toward nucleophilic thiols. The application of these structure\u2013activity data is a key one, because biological activity (i.e., micromolar levels) can be efficiently realized. Also, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance. Moreover, exploiting the release of trifluoroacetate enabled this selective modification to the structure of the natural product, eburnamonine. Lastly, the robustness and simplicity of quantitative analysis by NMR, which can be done readily without the use of deuterated solvents, were demonstrated by in situ monitoring of the consumption of reactant and formation of product. This NMR approach can gather mechanistic and kinetic data simultaneously, and presents a unique opportunity to examine complex systems at the interface of chemistry and biology.
", "answer": "The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (\\xe2\\x88\\x92)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance.", "id": 119} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfrom msm who attended the amsterdam municipal health service sti outpatient clinic in 2000 and 2001 , randomly selected stored specimens of c. trachomatis dna positive ( as assessed by ligase chain reaction , abbott laboratories , chicago , il , usa ) rectal samples were tested for the c. trachomatis variant by real - time pcr ( 6 ) . from 2002 to 2005 , msm with symptomatic proctitis ( i.e. , purulent discharge , rectal ulceration , bleeding , or edematous mucosa ) and msm without symptoms were included . from the san francisco region , 51 lgv positive isolates from symptomatic msm were analyzed ( 7 ) .\nthe isolates were collected in medical clinics ( e.g. , ambulatory care , emergency room , screening , acute care ) from 1979 to 1985 ( table ) .\nlgv was assessed at the time of collection , according to phenotypic properties observed during cell culture .\nalthough the growth characteristics of lgv serovars can be distinguished from serovars d k , cell culture for c. trachomatis is no longer available in most clinical settings . * in 2002 and 2003 , 45 lgv l2b variants of 109 isolates have been described in detail ( 5 ) . c. trachomatis serovar typing was performed as described previously ( 5 ) .\nbriefly , amplification of the ompa gene ( 1.1 kb ) was performed in a nested pcr format .\nthe ompa nucleotide sequences were subsequently analyzed by automated dna sequencing on an abi 310 sequencer ( pe biosystems , foster city , ca , usa ) .\nthe sequences obtained from c. trachomatis infected msm in 2000 and 2001 in amsterdam and from msm in san francisco were compared to the recently identified l2b variant to determine if the strain was present earlier .\nthe table presents the results of this analysis . in the amsterdam c. trachomatis dna positive rectal samples ,\nlgv strains were detected by real - time pcr in 2 of 67 samples in 2000 and in 4 of 28 samples in 2001 .\nsequencing showed that in all 6 lgv strain positive samples , the l2b variant was present .\nalso in 2002 and 2003 , 109 l2b - positive samples of 403 c. trachomatis dna positive rectal samples were identified , of which 45 were strain l2b , and these have been described in a previous publication ( 5 ) .\nall 51 san francisco specimens ( from 51 patients ) were positive for lgv variants by real - time pcr . by sequencing variable segment 2 of the ompa gene ( vs-2 )\n, we identified 15 as serovar l1 , 18 as serovar l2 prototype , and 18 as the l2b variant .\nwe sequenced the complete ompa gene of 5 of these 18 l2b variants that originated in san francisco ; all were identical to the recently described l2b variant circulating in amsterdam .\nfour nucleotide changes were found when compared to reference serovars l2 , l2a , and the variant l2 , including 1 change that encoded the previously undescribed change at amino acid 162 , aatagt ( 5 ) .\nthe l2b lgv variant identified as the cause of all the lgv proctitis in the recent outbreak among msm in amsterdam appears to have been circulating in amsterdam in 2000 .\nmoreover , we showed that this l2b variant was present in the 1980s in san francisco with exactly the same mutations in the complete ompa gene .\nhowever , since we only sequenced the ompa gene , and although the sequence was identical in old and new l2b strains , we can not exclude the possibility that it could involve different strains of c. trachomatis that differ in other parts of the genome , although this is unlikely .\nsince lgv causes potentially severe infections with possibly irreversible sequelae if adequate treatment is not begun promptly , early and accurate diagnosis is essential .\nsequence - based nucleic - acid tests that can discriminate between lgv serovars and less invasive c. trachomatis species can help detect cases and prevent further transmission of lgv . in conclusion , our results suggest that we are dealing with the same lgv variant > 25 years later , and the current lgv outbreak in industrialized countries has most likely been a slowly evolving epidemic with an organism that has gone unnoticed in the community for many years and is now being detected by new technologies .\nthe numbers detected in 2005 in amsterdam suggest that a considerable reservoir exists , which emphasizes the need for ongoing public health awareness .", "answer": "we traced the chlamydia trachomatis l2b variant in amsterdam and san francisco . \n all recent lymphogranuloma venereum cases in amsterdam were caused by the l2b variant . \n this variant was also present in the 1980s in san francisco . \n thus , the current \" outbreak \" is most likely a slowly evolving epidemic .", "id": 120} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nknowledge of the anatomy of root canal systems is an essential prerequisite for endodontic treatment .\nmany of the problems encountered during and after root canal treatment occur because of inadequate understanding of the pulp space anatomy .\nstudies on the internal and external anatomy of teeth have shown that anatomic variations can occur in all groups of teeth and can be extremely complex .\nthis applies to mandibular incisor teeth as well , as many dentists fail to recognize the presence of a second canal .\ncurrent knowledge of pulp space anatomy is based on research findings and individual case reports .\nthere is a lack of consistency in the reported prevalence of second canals in mandibular incisors.[15 ] the differences may be related to study design ( in vivo versus ex vivo ) , technique of canal identification ( radiographic examination , sectioning and clearing ) or to racial divergence .\nit is important to be familiar with variations in tooth anatomy and characteristic features in various racial groups , since such knowledge can aid location and negotiation of canals , as well as their subsequent management .\nadditionally , a number of studies have shown different trends in shape and number of roots and canals amongst the different races.[1368 ] these variations appear to be genetically determined and are important in tracing the racial origins of populations .\ndescriptions of the frequently occurring root canal systems of permanent teeth are based largely on studies conducted in europe and north america , and relate to teeth of mainly caucasian origin .\nthese descriptions may not be fully applicable to teeth of non- caucasian origin . there are no published reports on the root canal anatomy of mandibular incisors in north east indian population .\nhowever , some studies have examined an indian population . the north - eastern population in india is mostly comprised of indo - aryans ( caucasoid ) mongoloids ( tibeto - burman and paleo - mangoloid sub race ) and dravidian sub populations .\nthe population of north - east india is nearly 38 million , out of which tribal mongoloid population accounts for almost 42 - 45% of the total population .\na total of five hundred and thirty six extracted mandibular incisors were randomly collected from general dental clinics within north - eastern india.out of the collected teeth , fifty six teeth were excluded because of immature or resorbed apices and four hundred and eighty teeth were selected for the present study . the gender and age of patients was not known , and no attempt was made to differentiate between central and lateral incisors .\nthe samples were stored in 5.25% sodium hypochlorite ( organo bio tech laboratories pvt ltd new delhi , india ) for 30 minutes for the removal of organic debris , and then in 10% formaldehyde until use .\nthe teeth were cleaned under running water , access cavities were prepared and the coronal pulp tissue extirpated in the canal orifices .\nthe samples were stored in 5% nitric acid solution ( aries laboratories , india ) for 5 days .\ndemineralization was assessed by the insertion of a paper pin in the crown and with the help of radiographs .\nthe samples were then rinsed under running water for 4 hours and placed in 70 , 80 and 95% ethyl alcohol successively , for 1 day . at the end of this period ,\nthe clearing procedure was completed by placing the samples in methyl salicylate ( regent chemicals , mumbai ) ) . at the end of the third day , complete transparency was achieved .\nindia ink ( united ink and varnishes pvt ltd , mumbai , india ) was injected into the root canals of the transparent teeth using syringes with 27 gauge needle ( shree uniya surgical , india ) . after the ink had dried , root canal morphology was examined by a magnifying glass of 5x magnification [ figure 1 ] , and the following observations were made : transparent specimen showing canal bifurcation \n number and type of root canals , presence and location of lateral canals and intercanal communications , location of apical foramina , andbifurcation of canals.canals were categorized into the first five types of vertucci 's classification as follows : \n type i : a single canal is present from the pulp chamber to the apex.type ii : two separate canals leave the pulp chamber , but join to form one canal to the site of exiting.type iii : one canal leaves the pulp chamber , divides into two within the root , and then merges to exit in one canal.type iv : two separate and distinct canals are present from the pulp chamber to the apex.type v : single canal leaving the pulp chamber but dividing into two separate canals with two separate apical foramina . \n\n number and type of root canals , presence and location of lateral canals and intercanal communications , location of apical foramina , and bifurcation of canals .\ncanals were categorized into the first five types of vertucci 's classification as follows : \n type i : a single canal is present from the pulp chamber to the apex.type ii : two separate canals leave the pulp chamber , but join to form one canal to the site of exiting.type iii : one canal leaves the pulp chamber , divides into two within the root , and then merges to exit in one canal.type iv : two separate and distinct canals are present from the pulp chamber to the apex.type v : single canal leaving the pulp chamber but dividing into two separate canals with two separate apical foramina . \n \ntype i : a single canal is present from the pulp chamber to the apex .\ntype ii : two separate canals leave the pulp chamber , but join to form one canal to the site of exiting .\ntype iii : one canal leaves the pulp chamber , divides into two within the root , and then merges to exit in one canal .\ntype iv : two separate and distinct canals are present from the pulp chamber to the apex .\ntype v : single canal leaving the pulp chamber but dividing into two separate canals with two separate apical foramina .\nresults of this investigation indicate that one third of the teeth exhibit two canal system ( 36% ) . of the teeth with two canals ,\ntype iii configuration was most common followed by type ii and type v [ figure 2 ] .\nalthough two canals were found in 36% of teeth , only 6.25% of canals exited in two separate foramina ( type v ) [ table 1 ] . out of all the canals showing two canal configuration , around 83% joined and exited in single foramen ( type ii and iii ) and remaining 17% exited in two separate foramina ( type v ) [ table 1].the apical foramen was found to coincide with the apical root tip in 47.2% of teeth [ table 2 ] . in the present study\n, lateral canals were observed in around 13% of the cases [ figure 3 ] [ table 3 ] .\nanastomosis were found only in type iii canals which accounts for 2.5% of all the teeth [ table 4 ] .\napical ramifications were seen in around 7.42% of the teeth , out of which 75.7% were with two rami , 24.3%with three rami , and none with four rami [ table 4 ] [ figure 4 ] . in teeth with two canals ,\nbifurcations were seen maximum in middle third ( 64% ) followed by in cervical third 23.3% and in apical third 1.25 % [ table 5 ] .\nintercanal communications were observed in 28.4% of all teeth and in 70.2% of teeth with two canals [ table 6 ] .\ncanal configuration ( from left to right ) types i , ii , iii and v number and percentage of canal system types in mandibular incisors ( n=480 ) in the study distribution of apical foramen in mandibular incisors ( n=480 ) in the study curvatures in type i canal configurations- straight , s shaped and j shaped distribution of lateral canals in mandibular incisors in the study distribution of apical ramification in mandibular incisors in the study type i variations- apical ramification , reticular structure and lateral canals distribution of position of canal bifurcation in mandibular incisors in the study distribution of intercanal communications in mandibular incisors in the study\nvarious methods have been used to study root canal morphology including radiographic examination , root sectioning , staining and clearing techniques , direct observation with microscope , sectioning and macroscopic observation , stereo microscope , spiral computed tomography , and cone beam computed tomography .\nvertucci used the clearing technique to study the root canal morphology of extracted mandibular anterior teeth .\nit has been reported that fine details of the root canal system can be visualized by staining and clearing[figure 1 ] .\nthis technique also makes canal negotiation with instruments unnecessary , thereby maintaining the original form and relation of canals , and provides a three - dimensional view of root canal .\nthe process of changing the tooth into a transparent object involves many physical and chemical changes .\nthe inorganic constituents of the tooth are first dissolved by decalcification , and further water , air , and lipid components are removed by dehydration and by subsequent immersion in the clearing agents , th and this method was used in the present study as well .\nthe literature on mandibular incisors reveals that 1168% of mandibular incisors possess two canals , although in many of these cases , the canals merge into one in the apical 13 mm of the root .\nvertucci examined the root canal morphology of 300 mandibular anterior teeth and reported a second canal in 27.5% of mandibular incisors .\nmiyashita et al . , reported that 12.4% of mandibular incisors contained two canals ; however , only 3% had two foramina .\nsert et al . , noted that two canals were present in 68% of mandibular central incisors .\nmauger et al . , evaluated the canal morphology at different root levels in one hundred mandibular incisors , and reported that 98100% of the teeth had one canal in the area 13 mm from the apex .\nthe differences between these morphology studies may be related to variations of examination methods , classification systems , sample sizes and ethnic background of tooth sources . in a study in jordanian population , it was found that 73.8% of the mandibular incisors possessed a single root canal , and 26.2% of teeth were with two canals .\nthe results of the present study indicate that one third of the teeth exhibit two canal system ( 36% ) [ table 2 ] [ figure 2 ] .\nit was found that 63.75% of mandibular incisors possessed a single root canal ( type i ) with straight , j and s shaped curvatures [ figure 3 ] as well as frequent apical ramifications , lateral canals and reticular structures [ figure 4 ] .\nonly 6.25% of canals exited in two separate foramina ( type v ) . of the teeth with two canals ,\ntype iii configuration was most common followed by type ii and type v. therefore , the frequency of two canals in the present study was within the range of previous reports .\nthis is due to failure of the dentist to recognize the presence of the second canal , and the need for access cavities to have appropriate inciso - gingival extension to facilitate the location of lingual canals .\nnone of the teeth were seen with type iv canal system , which may be due to smaller number of samples examined in the present study and any conclusion drawn needs to be based on study of a larger population .\nthe apical foramen was found to coincide with the apical root tip in 47.2% of teeth [ table 2 ] .\nthis is higher than reported in previous studies that demonstrated that the apical foramen coincided with the anatomical apex in 1746% of cases . in the present study , total apical foramen count stands at 510 ( n=480 ) , which is because of type v canal configuration and apical ramifications\nthis finding may be of significance in working length determination which often depends on the average position of the apical constriction relative to root apex . in the present study , lateral canals were observed in around 13% of teeth and were found most frequently in the middle of the canal [ table 3 ] [ figure 4 ] .\nlateral canals in the apical third account for 2.94%.this is consistent with the findings of miyashita et al . ; however , much lower than that reported by vertucci .\nanastomoses were found only in type iii canals which accounts for 2.5% of all the teeth .\napical ramifications were seen in around 7.42% of the teeth out of which 75.7% were with two rami , and 24.3% with three rami , and none with four rami [ table 4 ] . in teeth with two canals ,\nbifurcations were seen maximum in middle third ( 64% ) followed by the cervical third 23.3% ; and , the apical third 1.25% [ table 5].this requires an individualized procedure for preparation and filling in each of these conditions to obtain the most desirable results .\npulp space anatomy of mandibular incisors in an indian population show high incidence of complexity which includes variations in canal configuration , number of canals and presence of isthmus .\nintercanal communications were observed in 28.4% of all teeth , and in 70.2% of teeth with two canals [ table 6 ] .\nthe high percentage of intercanal communications in teeth with two canals may be of clinical significance , because it may be difficult to debride and fill these communications adequately .\nwithin the limitations of the present study , it can be concluded that overall , 36% of mandibular incisors in this north - east indian population had two canals . in the teeth with two canals ,\nthe type iii canal system was the most prevalent followed by type ii.type v was the least prevalent .", "answer": "aim : to aim of this study is to investigate the root canal characteristics of mandibular incisors in a north east indian population using a canal staining and tooth - clearing technique.materials and methods : four hundred and eighty extracted mandibular incisors , collected from dental clinics within north east india were selected for this study . following pulp tissue removal , \n the teeth were decalcified with 5% nitric acid , dehydrated with ascending concentrations of alcohol and rendered clear by immersion in methyl salicylate . after staining of the canal systems with india ink , cleared teeth \n were examined under 5x magnification and the following features were evaluated : ( i ) number and type of root canals ; ( ii ) presence and location of lateral canals and intercanal communications ; ( iii ) location of apical foramina ; and , ( iv ) bifurcation of canals.results:the majority of mandibular incisors had a single canal ( 63.75% of teeth possessed a type i canal system ) . \n although 36.25% of the roots possessed two canals , only 6.25% had two separate apical foramina.conclusions:the prevalence of two canals in this group ( of north east indians ) of mandibular incisors was 36.25% and is within the range of previous studies performed on populations of different racial origin .", "id": 121} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlactic acid was first found and described in sour milk by the swedish chemist karl wilhelm scheele ( 17421786 ) in 1780 .\nthe swedish chemist jns jakob berzelius ( 17791848 ) found lactic acid in fluid extracted from meat in 1808 [ 2 , 3 ] , and the german chemist justus von liebig ( 18031873 ) , who established the world 's first school of chemistry at giessen , proved that lactic acid was always present in muscular tissue of dead organisms . in 1859 , emil heinrich du bois - reymond ( 18181896 ) published several articles on the influence of lactic acid on muscle contraction [ 59 ] .\naraki and zillessen found that if they interrupted oxygen supply to muscles in mammals and birds , lactic acid was formed and increased [ 1014 ] .\nthis was the first demonstration of the relationship between tissue hypoxia and the formation of lactate .\nthe occurrence of increased lactic acid in blood ( hyperlactataemia ) nowadays reflects severe illness , in which the increased blood lactate levels may result from both anaerobic and aerobic production or from a decreased clearance .\nit was the german physician chemist johann joseph scherer who first demonstrated the occurrence of lactic acid in human blood under pathological conditions after death in 1843 and 1851 [ 15 , 17 ] , and carl folwarczny in 1858 who first demonstrated lactic acid in blood of a living patient . in this article\nwe wish to honour scherer 's forgotten observations and describe the influence of his finding on further research on lactic acid at the end of the 19th century .\nborn on 18 march 1814 in aschaffenburg , germany , scherer studied medicine , chemistry , geology and mineralogy at the university of wrzburg between 1833 and 1836 .\nhe obtained his phd in medicine and surgery in 1838 with a thesis entitled versuche ber die wirkung einiger gifte auf verscheidene thierclassen \nhe practised medicine in wipfeld , but inspired by the chemist ernst von bibra ( 18061878 ) he completed his studies in chemistry at the university of munich between 18381840 . in 1840\nhe was employed at the laboratory of justus liebig at giessen , and became professor at the medical faculty in 1842 , professor of organic chemistry in 1847 , and later professor of general , anorganic and pharmaceutical chemistry .\nhis work especially concerned quantitative research on blood and urine in pathological conditions . in 1843\nhe published his book chemische und mikroskopische untersuchungen zur pathologie angestellt an den kliniken des julius - hospitales zu wrzburg ( chemical and microscopic investigations of pathology carried out at the julius clinic at wrzburg ) ( fig . 1 )\n, in which he described 72 case reports , giving details on clinical course , diagnosis , and results obtained during autopsy and analysis of body fluids .\nin one chapter in his 1843 book entitled ' untersuchungen von krankhaften stoffen bei der i m winter 18421843 in wrzburg und der umgegend herrschenden puerperal - fieber - epidemie ' ( investigations of pathological substances obtained during the epidemic of puerperal fever which occurred in the winter of 18421843 in and around wrzburg ) scherer described the cases of seven young women who all died peripartum .\none of the women , the 23-year - old primipara eva rumpel , gave birth to a healthy child on 9 january 1843 .\nthe same night she developed a painfully swollen abdomen and became ill , feverish , and sweaty , with rapid pulse and severe thirst .\nthe next evening she deteriorated , became delirious , with anxious breathing , a tense abdomen , cold extremities and rapid pulse , finally losing consciousness .\na.m. , 36 h after the onset of the first symptoms , she died . during autopsy\n, severe purulent endometritis , vaginal pus , pulmonary oedema , and shock liver and shock spleen were found .\nthe blood that was obtained directly from the heart was chemically analysed , in which lactic acid was found .\nmost likely this unfortunate woman had died from a fulminant septic shock caused by group a haemolytic streptococci ( streptococcus pyogenes ) .\nanother patient , the 28-year - old , 7 months pregnant ( second pregnancy ) margaretha glck , was , after being icteric , nauseous , vomiting and complaining about epigastric pain for 8 days , admitted to the lying - in birth clinic on 6 february 1843 .\nfour days later she was transferred to the hospital with severe nosebleeds and generalised exanthema or purpura . in the evening she suffered from severe gastric bleeding and epistaxis , showing rapid pulse , cold extremities and dizziness . the next morning\n, she was transferred back to the birth clinic , where she gave birth to a premature child ( 30 weeks ) and suffered from a severe post - partum fluxus .\nshe was again transferred to the hospital with the following symptoms : cold clammy skin , tachycardia , severe lochia and persistent exanthema or purpura , but without signs of an acute abdomen . during the night of february 11\nautopsy revealed a small intracerebral haematoma , normal lungs without pulmonary oedema , ascites and an anaemic , foul smelling uterus filled with purulent and decayed tissue and pus .\nblood was also obtained directly from the heart during autopsy and lactic acid was found . in this case\nwe could think of a haemorrhagic shock and cerebral haemorrhage due to clotting disorders possibly resulting from either acute fatty liver of pregnancy / hellp syndrome , idiopathic thrombocytopenic purpura , thrombotic microangiopathy ( ttp / hus ) or dic .\nin the conclusions of his 1843 book , scherer attached high importance to the fact that he found lactic acid in cases of puerperal fever , which he had not found before in healthy persons .\nhe held the opinion that lactic acid was formed in blood during bodily deterioration in severe diseases like puerperal fever .\nlactic acid was thus described for the first time in human blood and was demonstrated for the first time as a symptom of septic and haemorrhagic shock . in the same period a junior obstetrician in vienna , ignaz philipp semmelweis ( 18181865 ) , discovered in 1847 that physicians carried infectious particles on their hands from the mortuary to the obstetrical clinic , causing puerperal fever and puerperal sepsis , and he introduced a successful method for its prevention .\nlouis pasteur ( 18221894 ) found in 1879 that infection with streptococci was the most important cause of puerperal fever .\nscherer worked closely with the famous pathologist rudolf virchow ( 18211902 ) on several projects ( fig . 2 ) . in 1851\nvirchow performed an autopsy on a patient who had died from leukaemia and offered scherer blood from this patient for analysis .\nthe results of this analysis were published the same year in the verhandlungen der physikalisch - medicinischen gesellschaft in wrzburg .\nvirchow and scherer had previously studied the spleens of patients who died from leukaemia , and were curious if they could find the same results in the blood .\nscherer reached the conclusion that : the blood of this patient contains : ameisensure , essigsure und milchsure , die gleichfalls von mir schon frher als in der milzflssigkeit vorkommend bezeichnet wurden \n( formic acid , acetic acid , and lactic acid , as also found by me previously in fluids from the spleen ) . \n\n2johann joseph scherer ( left ) and rudolf virchow ( right ) in 1849 johann joseph scherer ( left ) and rudolf virchow ( right ) in 1849\nscherer 's observations inspired others to conduct further research , primarily in patients with leukaemia [ 1922 ] , but also in patients with other conditions and diseases and in animal experiments with dogs and rabbits .\nwhile scherer found lactic acid in blood obtained after death during autopsy , mosler and krner mention an observation made by carl folwarczny , published in the allgemeinen wiener medicinischen zeitung in 1858 , where blood was withdrawn from a leukaemia patient during life , analysed according to scherer 's method , and found positive for lactic acid . in addition , carl folwarczny described in 1863 in his ' handbuch der physiologischen chemie ' that lactic acid can be found in the blood of patients with leukaemia , septicaemia ( pyaemia ) and in conditions leading to septicaemia like puerperal fever , the latter probably after scherer 's observations . in an extensive article , the berliner physician georg salomon , who had serious doubts that the occurrence of lactic acid in blood was mostly related to leukaemia , proved in 1878 that lactic acid was also present in the blood of patients who were suffering and died from other diseases .\nhe studied blood obtained during autopsy from cadavers , but also blood from patients obtained by bloodletting or cupping , and in some cases he compared the blood before and after death .\nhe was able to demonstrate lactic acid in the blood of patients suffering from leukaemia , ( pernicious ) anaemia , congestive heart failure , chronic obstructive pulmonary disease , pleuritis , pericarditis , pneumonia and several solid malignant tumours .\ngaglio is often erroneously mentioned as the first author to find lactic acid in blood [ 2729 ] .\nhe was able to demonstrate lactic acid in fresh arterial blood withdrawn from dogs and rabbits after bloodletting .\nboth gaglio and berlinerblau , however , neglected previous research , as indignantly described by salomon in 1888 [ ich erlaube mir , den inhalt meiner arbeiten , die von gaglio nur ganz flchtig , von berlinerblau gar nicht berhrt sind , in krze zu reproduciren \n( i take the liberty of summarizing the contents of my work , which was mentioned only briefly by gaglio and not at all by berlinerblau ) ] .\nthe japanese chemist trasaburo araki showed that the amount of lactic acid in exhausted muscle results from muscle activation .\nirisawa , inspired by the results obtained by salomon and gaglio , obtained fresh blood of 11 dying patients with serious conditions . in six cases he found hyperlactataemia , in four cases normal values .\nhe speculated on the aetiology of hyperlactataemia , the most plausible cause being the severe hypoxia during the dying process . in an experiment in which he made a dog anaemic for several days\n, he found a rise in lactic acid levels during the time leading up to death . in cambridge ( uk ) ,\nwalter morley fletcher ( 18731933 ) and frederick gowland hopkins ( 18611947 ) worked together on the metabolic changes occurring in muscular contractions and rigor mortis under anaerobic conditions , and found that lactate was the product of carbohydrate metabolism .\ntheir classic 1907 paper demonstrated rigorously that muscle contraction is accompanied by the anaerobic formation of lactic acid , which is removed aerobically , at a rate depending on the level of exposure to oxygen .\npoul astrup and john severingshaus mentioned scherer 's 1851 article as first demonstration of lactic acid in blood , but overlooked the 1843 cases and folwarczny 's work . in conclusion , scherer 's 1843 case reports should be cited as the first description of lactic acid in human blood and also as the first demonstration of lactic acid as a pathological finding in septic and haemorrhagic shock .\nfolwarczny , in 1858 , was the first to demonstrate lactic acid in blood in a living patient .", "answer": "lactic acid was first found and described in sour milk by karl wilhelm scheele ( 17421786 ) in 1780 . the german physician \n chemist johann joseph scherer ( 18411869 ) demonstrated the occurrence of lactic acid in human blood under pathological conditions in 1843 and 1851 . in this article \n we honour the forgotten observations by scherer and describe the influence of scherer 's finding on further research on lactic acid at the end of the 19th century . \n we conclude that scherer 's 1843 case reports should be cited as the first description of lactic acid in human blood after death and also as the first demonstration of lactic acid as a pathological finding in septic and haemorrhagic shock . \n carl folwarczny was , in 1858 , the first to demonstrate lactic acid in blood in a living patient .", "id": 122} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfixed drug eruption ( fde ) is characterized by recurrent well - defined lesions in the same location each time the responsible drug is taken .\nwe report here a rare case of fde induced by atenolol , a beta - adrenoreceptor - blocking agent .\na 48-year - old tunisian woman was referred to our department for the appearance of five inflammatory plaques on both legs .\nshe had been treated for hypertension with atenolol ( hypoten , al - hikma pharmaceuticals , jordan ) 100 mg once a day for six weeks .\nno other medications had been taken and she had not previously received beta - blocking agents .\nphysical examination revealed five well - demarcated reddish and round plaques with an itching and burning sensation on both legs ( figure 1 ) .\nskin biopsy , taken from a lesion with no vesicular changes , showed focal necrosis of keratinocytes , hydropic degeneration of the basal cells , dermal edema and a perivascular lymphocytic infiltrate of the upper dermis .\ntopical desonide ( locatop ) was applied twice a day and skin lesions resolved within two weeks with a residual pigmentation .\n6 weeks after complete resolution , patch testing was carried out according to the international contact dermatitis research group ( jacobs et al 1999 ) recommendations with 10% atenolol in petrolatum on a previously affected site of the right leg ( figure 2 ) and on normal skin of the back . a positive reaction ( + + )\nwas seen at d2 and d3 on the left leg but no reaction was detected on the back .\nthey mostly include nonsteroidal antiinflammatory drugs , nonopioid analgesics , sulphonamides , and tetracyclines ( savin 2001 ) .\ntopical provocation testing has been reported to be useful and safe for the diagnosis of fde when applied on previously affected sites ( alanko et al 1987 ; alanko 1994 ; lee 1998 ; ozkaya - bayazit et al 1999 ) .\ndifferent patch test methods ( open / occlusive ) and variations in their evaluation ( erythema of more than six hours duration / erythema and infiltration ) exist ( ozkaya 2008 ) .\nbeta - blockers - induced fde are very rare ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) .\nonly two cases have been reported in the literature ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) .\nthey were induced by atenolol ( palungwachira and palungwachira 1999 ) and propranolol ( zaccaria et al 2006 ) .\nnone of them was confirmed by patch testing or systemic provocation ( palungwachira and palungwachira 1999 ; zaccaria et al 2006 ) .\nthus , to the best of our knowledge , we report herein the first case of fde induced by atenolol and confirmed by a positive patch test on previously affected sites .", "answer": "fixed drug eruption ( fde ) is characterized by recurrent well - defined lesions in the same location each time the responsible drug is taken . \n we report here a case of multiple fde induced by atenolol in a 48-year - old woman confirmed by positive patch test in previously affected sites . \n beta - blockers - induced fde are very rare . \n only two cases had been reported in the literature . to the best of our knowledge , \n this is the first case reported of atenolol - induced fde confirmed by a positive patch test .", "id": 123} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nour survey covered all small molecule new molecular entity ( nme ) drugs that are intended for systemic use and were approved by the fda between january 2013 and august 2016 . the new drug application ( nda ) review documents ( drugs@fda , http://www.fda.gov/drugsatfda ) and product labels were examined for pbpkrelated information for the 85 products that met the above criteria .\nthere were a total of 18 products for which pbpk models were considered in the nda review documents ( tables \n 14 ) . in the majority of cases , pbpk models were used for the prediction of the effect of metabolic enzyme mediated drugdrug interactions ( ddis ; figure \n 1a ; tables \n 14 ) .\nimportantly , the frequency of model use is consistent with the perceived level of reliability.1 , 3 , 5 \n overview of physiologically based pharmacokinetic ( pbpk ) information in product labels or us food and drug administration ( fda ) review documents for drugs approved by the fda between january 2013 and august 2016 .\n( a ) number of new molecular entities ( nmes ) with information of pbpk for respective areas of applications .\n( b ) proportion of product labels / reviews containing pbpk information for drugs in all nmes , anticancer agents , and nmes with breakthrough therapy designation and/or accelerated approval status at the time of approval .\nseven of eight nmes with pbpk and breakthrough / accelerated approval status were anticancer agents .\na key caveat of our survey was that it was limited to publicly available information .\nthe utilization of pbpk models for sponsor 's internal decisionmaking and earlier stage and postapproval regulatory interactions , such as postmarketing requirement ( pmr ) or supplementary nda , were not captured .\npbpk models have great potential to influence decisionmaking at different stages of drug development , such as initial dosing recommendations for pediatric clinical trials , design of ddi studies , etc.5 the current evaluation should be interpreted in the context of pbpk use during the final phase in the development of a new drug , because pbpk modeling strategies and the level of model validation can vary at different stages of drug development .\nthis survey also did not capture the potential value of cost and speed savings by using pbpk vs. conducting clinical studies .\ninterestingly , we observed wider acceptance of pbpk models in the field of oncology compared with other therapeutic areas ( figure \n 1b ) . one possible explanation is the difficulty of conducting clinical ddi studies in oncology , due to ( 1 ) shortage of appropriate patient populations or ( 2 ) ethical and safety concerns over exposing healthy volunteers to oncology medications .\nthe first point is supported by the observation that three of eight nmes with pbpk in the nononcology field were for rare diseases ( such as eliglustat , macitentan , and obeticholic acid ) .\nanother possible explanation is that the higher levels of toxicity and narrower therapeutic windows for oncology drugs compared with drugs in other therapeutic areas warrant precise optimization of drug exposure .\nit is also noteworthy that 7 of 10 anticancer agents were given regulatory incentives to accelerate drug development , either with breakthrough therapy designation or accelerated approval , which may have contributed to a greater reliance on pbpk simulations .\npbpk models have been most extensively used for the prediction of the effect of ddi or pharmacogenetic effect on the pharmacokinetics of nme as a victim ( figure \n 1a ) . in particular , the extrapolation of the effect of strong inhibitors or inducers to less potent perpetrators constituted the majority of the applications ( 11 among 13 nmes ; table \n 1 , ids 111 ) , and all applications resulted in labeling recommendations ( table \n 1 ) . in these cases , existing clinical data with strong perpetrator(s ) were used to anchor the pbpk model performance , namely by accurately providing fraction metabolized by a particular enzyme , which provides a higher level of confidence in ddi prediction.1 , 5 for example , a fourfold dose reduction of ibrutinib was recommended for patients taking moderate cytochrome p450 ( cyp)3a inhibitors based on the pbpk model validated with clinical ddi data using strong perpetrators .\npbpk models in product labels or fda review documents : new drug as a victim of ddis or genetic variations cyp , cytochrome ; ddi , drugdrug interaction ; i d , identification ; nme , new molecular entity ; pbpk , physiologically based pharmacokinetic ; pmc , postmarketing commitment ; pmr , postmarketing requirement ; ugt1a1 , udpglucuronosyltransferase 1a1 .\nthe numbers in the reference column represent pubmed i d ( if physiologically based pharmacokinetic models were published in scientific journals ) .\nthe elimination pathways for all the 11 nmes involve cyp3amediated metabolism , whereas two are metabolized by cyp2d6 in addition to cyp3a .\nthis observation is not surprising , considering that cyp3a and cyp2d6 are involved in metabolism of a large proportion of marketed drugs , and wellestablished probe perpetrators are available for these two enzymes . for two cyp3a and cyp2d6 dual substrates , aripiprazole lauroxil and eliglustat , complex interactions involving the inhibitors of these enzymes and cyp2d6 genotype\nanchoring of model prediction with both a strong inhibitor and an inducer has been conducted in most cases , but there were two cases in which model validation with inhibitors was used for the prediction of inducer effect ( cobimetinib , panobinostat ) , both of which resulted in a conservative labeling language of avoiding concomitant use with the strong inducers .\nthis may suggest that the required level of pbpk model qualification depends on the context of pbpk application . because modification of recommended dose in the product label\napplication of pbpk,2 the use of a certain amount of clinical pharmacokinetic data as an external validation dataset has generally been required for including dosing recommendations in the product label .\nthe case of belinostat is intriguingalthough there were no external data , the simulation performed by the fda during the nda review resulted in label language recommending a 25% reduction in the starting dose for homozygous carriers of a genetic polymorphism of its major metabolic enzyme , udpglucuronosyltransferase 1a1 .\nthis is likely , in part , because the recommended starting dose is equal to the maximum tolerated dose .\npmr to definitively examine the effect of pharmacogenetic alteration on belinostat pharmacokinetics and safety was included in the nda approval .\ntherefore , even when the pbpk approach could not obviate the conduct of a dedicated clinical study , the model can inform the optimal use of medications .\nthe second most frequent use of pbpk modeling is to predict the ddi potency of an nme as a perpetrator ( inhibitor / inducer ; table \n 2 ) .\nfour nmes ( ids 1417 ) have successfully utilized a pbpk modeling approach to demonstrate the lack of a clinically significant effect on the metabolic pathways of interest for the particular drug .\none method was to use a negative clinical ddi result with other cyp enzymes as an external validation ( alectinib , panobinostat ) , whereas another was to use a sensitivity analysis on inhibition parameters ( alectinib , canagliflozin ) . in the case of lenvatinib ,\nan external model validation was seemingly not performed , presumably supported by general perception that pbpkbased prediction of mechanismbased inhibition leads to overestimation of ddis.5 these observations based on limited cases suggest that required levels of model validation could be flexible , and that we may expect wider application of pbpk in this category .\npbpk models in product labels or fda review documents : new drug as a perpetrator of drugdrug interactions cyp , cytochrome ; ddi , drugdrug interaction ; i d , identification ; mate , multidrug and toxin extrusion transporter ; nme , new molecular entity ; oct2 , organic cation transporter 2 ; pbpk , physiologically based pharmacokinetic ; pmc , postmarketing commitment ; pmr , postmarketing requirement .\nthe numbers in the reference column represent pubmed i d ( if physiologically based pharmacokinetic models were published in scientific journals ) .\nthere were two nmes with pbpk models for which additional dedicated clinical ddi studies with cyp3a substrates were requested as pmr . for ceritinib ,\nin addition , neither of these two nmes had supporting clinical data to verify model performance .\nfurther examples will be needed to evaluate the ability of the pbpk approach to quantitatively predict positive ddi effects.1 \n\nmost of the pbpk applications on absorptionrelated pharmacokinetic changes were exploratory and did not impact the labeling recommendation ( table \n 3 ) .\naltered panobinostat absorption was not observed with drugs that elevate the gastric ph in pbpk simulation .\npbpk models in product labels or fda review documents : drug absorption ara , acid reducing agents ; auc , area under the curve ; cmax , peak plasma concentration ; fda , us food and drug administration ; i d , identification ; nme , new molecular entity ; pbpk , physiologically based pharmacokinetic ; pgp , pglycoprotein .\nthe numbers in the reference column represent pubmed i d ( if pbpk models were published in scientific journals ) .\nother pbpk applications observed in the nda review documents include prediction of the effect of hepatic impairment ( hi ; table \n 4 ) , but pmrs were issued for three of four nmes to conduct or complete dedicated clinical studies , presumably because of the low level of reliability.1 in the case of obeticholic acid , the effect of hi on hepatic exposure was explored with pbpk simulations , and this helped to inform the dosing recommendation in patients with hi .\npbpk models in product labels or fda review documents : other areas of pbpk applications cyp , cytochrome ; ddi , drugdrug interaction ; hi , hepatic impairment ; i d , identification ; nme , new molecular entity ; oatp , organic aniontransporting polypeptide ; pbpk , physiologically based pharmacokinetic ; pmr , postmarketing requirement .\nthe numbers in the reference column represent pubmed i d ( if physiologically based pharmacokinetic [ pbpk ] models were published in scientific journals ) .\nthe regulatory impacts of pbpkbased predictions have been limited in areas other than metabolismbased ddis and pharmacogenetics , such as in transportermediated ddis or effect of acid reducing agents .\naccumulated experience of pbpk application in these areas will help to establish the level of confidence necessary to inform regulatory decisions .\nalso , some degree of model validation with clinical data using the nme has generally been required for highimpact regulatory decisions.2 currently , validation of system components , such as hepatic metabolic activity in patients with renal impairment , based on other molecules that share same elimination pathways has not been considered sufficient .\nsuch limitations have impeded the application of pbpk models to replace clinical studies for evaluating socalled intrinsic factors , such as in pediatric populations , to evaluate ethnic differences in pharmacokinetics , or in patient populations with organ impairment .\nthe authors believe that future verification efforts of pbpkbased prediction performance with cross learning from other molecules , including both xenobiotics and endogenous biomarkers , will greatly expand the use of pbpk beyond ddi and pharmacogenetic applications and will contribute to acceleration of new drug development .", "answer": "physiologically based pharmacokinetic ( pbpk ) modeling can be used to predict drug pharmacokinetics in virtual populations using models that integrate understanding of physiological systems . \n pbpk models have been widely utilized for predicting pharmacokinetics in clinically untested scenarios during drug applications and regulatory reviews in recent years . here , we provide a comprehensive review of the application of pbpk in new drug application ( nda ) review documents from the us food and drug administration ( fda ) in the past 4 years .", "id": 124} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndr . coyne - beasley receives research funding from merck & co. none of these funds were used in the conduction or completion of the research contained in this manuscript .\nthis article was supported by grants from the national institutes of health 1r01ai113305 - 01 ( cates pi ) , and by the north carolina translational and clinical sciences institute , through support from the national center for advancing translational sciences ( ncats ) , national institutes of health , grant award number 1ul1tr001111 .\nthe content is solely the responsibility of the authors and does not necessarily represent the official views of the nih .", "answer": "a significant barrier to the delivery of hpv vaccine is reluctance by both healthcare providers and parents to vaccinate at age 11 or 12 , which may be considered a young age . \n this barrier has been called vaccine hesitancy in recent research . in this commentary \n , we suggest using social marketing strategies to promote hpv vaccination at the recommended preteen ages . \n we emphasize a critical public health message of a sexually transmitted infection ( sti ) as preventable and vaccination against hpv as a way to protect against its consequences . \n the message tackles the issue of vaccine hesitancy head on , by saying that most people are at risk for hpv and there is a way to prevent hpv 's serious consequences of cancer . \n our approach to this conversation in the clinical setting is also to engage the preteen in a dialog with the parent and provider . \n we expect our emphasis on the risk of sti infection will not only lead to increased hpv vaccination at preteen ages but also lay important groundwork for clinical adoption of other sti vaccines in development ( hiv , hsv , chlamydia , and gonorrhea ) as well as begin conversations to promote sexual health .", "id": 125} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe report a case of sle - associated myopericarditis in a young male without clear evidence of viral infection based on viral markers in blood .\nthe patient 's cardiac function dramatically improved after treatment with steroids without any additional complications .\na 19-year - old male was admitted to the combined armed forces hospital with a 7-day history of fever , cough , dyspnea , orthopnea , and chest pain .\nbased on the chest radiograph and computed tomography , he was diagnosed with a pericardial effusion and pneumonia ( fig .\n1a ) , and was transferred to our hospital for evaluation of the cause and treatment .\nhis blood pressure was 110/70 mmhg , pulse rate was 112 beats / min , respiratory rate was 24 breaths / min , and body temperature was 38. jugular veins were engorged . on cardiac auscultation , the cardiac rhythm was regular and rapid , summation gallops were heard at the cardiac apex , and there were pericardial friction rubs along with left lower sternal border in the sitting position .\nbilateral pretibial pitting edema was present on admission . on admission , blood tests showed white blood cell count of 5,420/mm , hemoglobin 10.6 g / dl and platelet count of 94,000/mm .\nc - reactive protein was 4.59 mg / l ( normal , 0 - 3 mg / l ) .\nthe blood chemistry revealed blood urea nitrogen to be 24.0 mg / dl , creatinine 1.1 mg / dl , total protein 5.7 g / dl , and albumin 2.6 g / dl .\nthe levels of cardiac markers were elevated ; troponin - i 0.87 ng / ml ( normal , 0 - 0.05 ng / ml ) and myoglobin 371 ng / dl ( normal , 16.3 - 96.5 ng / dl ) .\nan electrocardiogram ( ecg ) revealed sinus tachycardia and diffuse t - wave inversion in which leads ( fig .\nechocardiography demonstrated severe left ventricular systolic dysfunction { left ventricular ejection fraction ( lvef ) was 18% } with severe global hypokinesia and preserved wall thickness ( fig .\na large amount of pericardial effusion was observed 13 mm anterior to the right ventricle , 18 mm around the right atrium and 2 mm posterior to the lv .\nat first , we suspected viral myopericarditis , and started conservative treatment for congestive heart failure and pericarditis .\nbut , there was no improvement in lvef as well as in the clinical findings . viral markers for cytomegalovirus , coxsackie virus b type 2 , herpes simplex virus , and epstein - barr virus were all negative . during conservative treatment\n, he complained of new - onset ankle joint pain and tender erythematous swellings in both the ankles .\nthe immunofluorescence tests were positive for anti - nuclear antibody ( 1 : 640 titre ) , anti - dsdna antibodies ( 683.4 iu / ml ) , and anti - extractable nuclear antigen antibodies ( anti - sm , anti - rnp , anti - ro , and anti - la ) , and the complement level was low ( table 1 ) .\nwe concluded that the patient had sle according to the american rheumatism association / american college of rheumatology classification criteria for sle . on the 13th day of admission\n, we started treatment with high - dose glucocorticoids ( methylprednisolone 1,000 mg intravenously daily for three days followed by 1 mg / kg per day in divided doses ) . on follow - up examination , ecg showed normalization of t - wave inversion ( fig . 2c ) and echocardiography obtained just before discharge showed improved systolic function ( fig .\nchest x - ray also showed improving consolidation in both the lung fields and cardiomegaly ( fig .\ncomplement 3 was normalized and anti - dsdna antibodies decreased from 683.4 iu / ml to 383.8 iu / ml ( who u / ml , normal 0 - 93 ) .\nhe was discharged on the 33rd day of admission with oral prednisolone , and he visited the outpatient department 1 month later . in this 1 month , he had no symptoms .\nechocardiography revealed normal lvef , without significant valvular disease and pericardial effusion compared to the last examination ( table 2 ) .\nsubsequently , the steroid medication was tapered and it was planned to maintain him on sle - specific treatment in the rheumatologic department .\nsle is an autoimmune inflammatory disease of unknown etiology that affects various parts of the body , including all components of the cardiovascular system.1 ) the prevalence of lupus ranges from approximately 40 - 150 cases per 100,000 in the usa.2 ) in adults , the female - to - male ratio is 7 - 15 : 1.3 ) cardiac involvement in sle may comprise of involvement of the pericardium , myocardium , endocardium , heart valves , and coronary or pulmonary arteries.4 ) pericardial involvement is the most frequent cause of symptomatic cardiac disease5 ) and is the most common echocardiographic finding in sle patients .\nthe pericardium can be involved by acute and chronic inflammatory changes ; granular deposition of immunoglobulin and c3 , demonstrated by direct immunofluorescence,6 ) supporting the role of immune complexes in the development of pericarditis .\nmyocarditis is an uncommon , often asymptomatic manifestation of sle with a prevalence of 8 - 25% in different studies.7 ) global hypokinesis may be an echocardiographic indication of myocarditis and is present in approximately 6% of sle patients.8 ) the gold standard for diagnosing myocarditis in sle remains the endomyocardial biopsy.9 ) however , an endomyocardial biopsy is invasive with procedure - related risks and the diagnostic yield is low in 10 - 20% of cases , so it is not powerful enough to confirm the diagnosis.10 ) lupus myocarditis can be diagnosed based on clinical suspicion and echocardiographic evidence of a reduced lvef and segmental or global wall motion abnormality , once the other etiologies , such as viral and ischemic cardiomyopathy , have been excluded.9)11 ) immunofluorescence studies demonstrate fine granular immune complexes and complement deposition in the walls and perivascular tissues of myocardial blood vessels , supporting the hypothesis that lupus myocarditis is an immune complex - mediated disease .\nlupus myocarditis , although mild , has to be treated immediately with high - dose corticosteroids . in the most severe forms ,\nit is necessary to use intravenous pulse corticosteroid therapy ( methylprednisolone 1 g / day for three consecutive days ) followed by high doses of oral prednisone .\nimmunosuppressants , namely cyclophosphamide or azathioprine , and intravenous igg may be beneficial in the treatment of myocarditis.5 ) early mechanical circulatory supports help to save the life and prevent multi - organ failures in patients with fulminant myocarditis.12 ) in the present case , the patient was initially diagnosed with myopericarditis on the basis of his symptoms , diffuse t - wave inversion on ecg , elevated cardiac markers and echocardiographic findings .\nhowever , there was no improvement in his symptoms and the common cardiotrophic viral markers were all negative . also , the patient had pericarditis , thrombocytopenia and proteinuria .\nbecause the previous typical clinical signs and the positive immunofluorescence tests were suitable for making the diagnosis of sle , we confirmed the diagnosis of myopericaditis associated with sle in this patient .\nafter a provisional diagnosis of myopericarditis with sle was made , he was treated with intravenous corticosteroid pulse therapy ( methylprednisolone 1 g / day for three consecutive days ) followed by high doses of oral prednisone .\nafter 3 days of steroid therapy , the patient 's signs and symptoms were stabilizing and echocardiographic findings were improved .\ninitially , we had considered myopericarditis to be caused by viral infection ; however , the final diagnosis was myopericarditis during presentation of primary sle based on the clinical manifestations , echocardiography , immunofluorescence tests and good response to steroid therapy . because the treatment of sle induced myopericarditis\nshould be needed for some specific therapy such as corticosteroid , this case shows that careful investigation is needed for search of the cause of myopericarditis in a young male , and not only viral infection but also autoimmune disease should be investigated for . in this report\n, we described the first case of a korean young male sle patient in whom the first manifestation was of myopericarditis and treatment with glucocorticoids resulted in a good clinical outcome .", "answer": "myocardial involvement with clinical symptoms is a rare manifestation of systemic lupus erythematosus ( sle ) , despite the relatively high prevalence of myocarditis at autopsies of sle patients . in this review , \n we report the case of a 19-year - old male sle patient who initially presented with myopericarditis and was successfully treated with high dose of glucocorticoids .", "id": 126} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nproliferative vitreoretinopathy ( pvr ) remains the major complication after retinal detachment surgery [ 13 ] .\npvr was identified as an independent clinical entity in 1983 by the retina society terminology committee and a classification was created , based on the condition formerly named massive vitreous traction or massive periretinal proliferation [ 57 ] .\nthis classification divided pvr into four stages , a , b , c , and d , apparently by increasing its severity , from minimal to massive pvr ( table 1 ) . nevertheless , this classification had numerous limitations .\nit did not consider the location of the vitreoretinal traction and the magnitude of the contraction .\nin addition , some of the stages provide a false idea of severity ; for instance , d4 caused by a localized epiretinal membrane could be more easily treated by surgery than a c1 caused by intraretinal changes [ 8 , 9 ] . in 1989 , the silicone study group introduced a new classification including some characteristics , such as the location , anterior or posterior , and the type of contraction ( table 2 ) .\nclassification was then updated in 1991 according to modifications proposed by the silicone study group and also by other authors ( table 3 ) .\nthis classification appears to be difficult to use in clinical practice and may not offer any special advantage for decision - making in relation to the treatment of the disease .\nmoreover , the classifications might have prevented advances in the understanding of the disease pathogenesis .\nfor instance , because the retina society committee defined pvr as a proliferative disease , many treatments based on the inhibition of cell proliferation were developed for more than 20 years , none of which appears to have produced a significant clinical advance .\ntherefore , a review of both the classification and the pathogenesis of pvr appears to be appropriate to aid the development of new treatments .\nthere is a clinical impression that over the last 15 years clinicians have abandoned current pvr classifications .\nthus , the purpose of this study has been to evaluate the current use of pvr classifications in papers dealing with clinical practice and therapy as an indirect measure of the degree of usefulness of existing classifications .\na search in pubmed for papers published between january 2000 and january 2014 was undertaken by two independent researchers .\ninclusion criteria comprised human studies published in english , french , and spanish on pvr or retinal detachment with specific mention to pvr .\nprospective randomized and nonrandomized clinical studies , retrospective clinical studies , short series , and pilot studies were included .\na manual search of related articles was also performed through references reported in each article .\nwe also analyzed how the different authors interpreted the classifications , comparing the results they provided with the original description .\ntherefore , we investigated if they used all the characteristics ( grade [ a , b , c ] , pvr localization , extension in hours , and type ) of the updated retina society classification or if they were used only partially .\nfurthermore , it was also noted whether classifications were used both before and after an eventual pvr pharmacological or surgical treatment .\ndata were extracted using a custom - made data sheet performed with agreement between authors .\npreliminary search identified a total of 219 publications , 81 of which were eliminated as they did not fulfill the inclusion criteria .\n35 articles ( 25,4% ) did not undergo detailed analysis because there was no reference to the type of pvr classification used by the authors or because no classification was used ( generic terms such as initial or severe pvr or simply pvr were adopted , without using any grading system ) .\n103 publications ( 74,6% ) used standardized pvr classifications and they were analyzed in detail .\nthe most used classification was the updated retina society classification ( 58 cites ; 56,3% ) , followed by the first retina society classification ( 35 cites ; 33,9% ) .\nin addition , 3 authors ( 2,9% ) used modified or customized classifications [ 1315 ] . in 4 publications ( 3,8% ) , errors in the stated classification\nwere identified [ 13 , 1618 ] : in two papers [ 16 , 18 ] , the authors cite the updated retina society ( 91 ) but in fact they used the first retina society classification ( 83 ) , koerner et al . , after citing the updated retina society classification used a customized one , and roldn - pallars et al .\ncite the two retina society classifications at the same time . among the papers using the updated retina society classification , the most documented was grade c pvr ( 48 articles , 83% ) , while grades b and a were less frequently documented ( 15 ( 26% ) and 7 ( 12% ) articles , resp . ) .\nof the publications documenting only c grade , the classification of subtypes was infrequently used . in 5 of 48 publications ( 10,4% )\n, there was a full c grade description in terms of localization ( anterior or posterior ) , extension ( in clock hours ) , and type ( focal , diffuse , subretinal , circumferential , or anterior displacement ) .\na similar finding was observed when authors used the first retina society classification ( 35 papers ) : only c and d grades were frequently reported ( 27 and 10 papers , resp . ) , while grades a and b were infrequently used ( 4 and 7 articles , resp . ) .\nwhen the silicone study classification was used , only grade c was mentioned ( in 2 out of 4 articles ) .\nfinally , there were 2 publications ( 1,9% ) in which the standard classifications were used to assess changes in pvr status after any treatment , reporting pvr grade before and after it [ 19 , 20 ] .\nthe remaining authors used the classifications only to describe pvr status , rather than using them to analyze the improvement or worsening of the previous stage after the applied treatment .\nclassifications of pvr were developed to provide clinicians with a useful tool to compare results of treatments .\nthey are , to date , purely descriptive and do not reflect the pathobiology of this complex vitreoretinal disease .\nthe original classification of 1983 , which was relatively simple to use , induces errors in the estimating severity in some cases .\nas mentioned , d grades were based on the ophthalmoscopic appearance of the detached retina , and experience demonstrated that some of these cases could be relatively easily solved by peeling localized epiretinal membranes although , in some cases , classified as c , intraretinal severe changes prevent reattachment , unless complicated surgical techniques were used .\nsubsequent classifications [ 10 , 11 ] were more detailed and therefore more complicated to use on a routine basis .\nthey incorporated the anterior pvr forms , which add severity to the case , but until now no one has incorporated the intraretinal changes , observed in many surgical retinal samples [ 8 , 9 ] , which may prevent the anatomical reattachment of the retina and require retinectomy .\nanother important limitation is that they do not provide information on the activity of the process , although it has been observed that pvr progresses through several stages [ 13 ] .\nthis may be crucial in estimating the risk of reproliferation after surgery or when surgeons schedule removing silicone oil , and no data on the chronology of events is included in any classification .\nfurthermore , current classifications are not prognostic and do not correlate with visual prognosis or anatomical success after surgical treatment\n. moreover , some of these classifications can be difficult to use in clinical practice , due to their complexity ( grade , localization , extension , type , etc . ) and because they may not provide useful information they have been largely abandoned by clinicians .\nour findings in this study demonstrate that , in clinical research , investigators are using them inconsistently and reporting limited observations of stages ( mostly grade c ) .\nsome authors simply do not use any , preferring generic terms , such as minimal , moderate , and severe pvr [ 21 , 22 ] .\nfurthermore , early stages of pvr ( named as grades a and b ) , which are common to all classifications , are not used , and most authors refer only to most advanced stages , basically grade c [ 20 , 23 ] . moreover\n, the presence of classification errors could indicate that there is confusion concerning their use [ 13 , 1618 ] .\nan important relevant finding is that only a limited number of clinicians appropriately and fully use the current updated classification of 1991 [ 2427 ] , while the majority of authors avoid using the added characteristics of localization , extension , and type , limiting the description to the grade .\nin addition , many colleagues still use the first reported classification , probably because although it presents many limitations , it is easier to use compared to the last version [ 23 , 28 ] .\nadditionally , some authors decided to use alternative classification , probably to avoid problems evaluating pvr stages .\nthe use of multiple classifications makes the efficient communication between clinicians and the comparison of different studies very problematic .\nas mentioned , one of the aims of this study was to evaluate the usefulness of these classifications for pvr management with surgery and other adjunctive treatments .\nunfortunately , many ophthalmologists did not use the normalized classifications for comparing the outcomes using non - clearly defined terms such as pvr recurrence [ 29 , 30 ] .\nour findings showed the inconsistent and limited use of the current pvr classifications suggesting that it may be of benefit to produce a revised classification incorporating , if possible , the new knowledge on pvr which has been published since 1991 , pointing out new potential targets for therapeutic agents distinct from those , mainly proliferative agents , targeted by the original description of this disease .\nthus , it is possible that we could reduce its prevalence after retinal detachment surgery and to improve the anatomical and functional results of this disease which resists the attempts of both basic researchers and clinicians for more than 30 years .", "answer": "purpose . to evaluate the current and suitable use of current proliferative vitreoretinopathy ( pvr ) classifications in clinical publications related to treatment \n . methods . \n a pubmed search was undertaken using the term proliferative vitreoretinopathy therapy . \n outcome parameters were the reported pvr classification and pvr grades . \n the way the classifications were used in comparison to the original description was analyzed . \n classification errors were also included . \n it was also noted whether classifications were used for comparison before and after pharmacological or surgical treatment . \n results . \n 138 papers were included . \n 35 of them ( 25.4% ) presented no classification reference or did not use any one . \n 103 publications ( 74.6% ) used a standardized classification . \n the updated retina society classification , the first retina society classification , and the silicone study classification were cited in 56.3% , 33.9% , and 3.8% papers , respectively . \n furthermore , 3 authors ( 2.9% ) used modified - customized classifications and 4 ( 3.8% ) classification errors were identified . \n when the updated retina society classification was used , only 10.4% of authors used a full c grade description . \n finally , only 2 authors reported pvr grade before and after treatment . conclusions . \n our findings suggest that current classifications are of limited value in clinical practice due to the inconsistent and limited use and that it may be of benefit to produce a revised classification .", "id": 127} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimitive neuroectodermal tumor ( pnet ) , a highly aggressive tumor of the kidney is a rare malignancy with only few cases being reported in literature .\nboys and men are more likely to suffer rpnet ( renal pnet ) , and the sex ratio ( male : female ) is about 3:1 .\nit usually presents at an advanced stage , with distant metastasis and is associated with a poor prognosis .\nwe report in this paper , a case of primary renal pnet in a young male .\na 39-year - old male presented with complaints of hematuria and heaviness in the right flank since 15 days . physical examination revealed a soft lump in the right hypochondrium .\nultrasound examination of the abdomen showed an irregular cystic structure in the right kidney at lower pole with few internal echoes .\nct scan of the abdomen demonstrated a large significantly enhancing right renal lower polar mass with necrosis with thrombosis in right renal vein . on the basis of these clinico - radiological findings , diagnosis of right side renal cell cancer\ngross examination revealed a friable , grayish - white , lobulated mass ( 7 5 cm ) with multiple foci of hemorrhage and necrosis .\nthe mass extended from mid to lower pole of the right kidney and infiltrated into the renal pelvis and was limited to the renal capsule the renal vein and ureter were free of the tumor .\nthere was a thrombus inside the renal vein , which was not adherent to intima of renal vein .\nmicroscopically , the tumor was composed of monotonous sheets of round cells with scant cytoplasm , hyperchromatic vesicular nuclei , coarse chromatin and few conspicuous nucleoli , transverse by thin fibrous bands infiltrating and entrapping the renal glomeruli and tubules [ figure 1 ] .\non immunohistochemistry , the tumor cells were positive for cd99 [ figure 2a ] , fli-1 [ figure 2b ] , nse [ figure 2c ] , and synaptophysin [ figure 2d ] , but negative for desmin , ck , ema , and lca .\na diagnosis of pnet was made based on the above findings , and patient was started on vac ( vincristine , adriamycin , and cyclophosphamide ) alternating with ie ( ifosfamide and etoposide)-based adjuvant chemotherapy regimen which he tolerated well .\nafter 6 cycles of chemotherapy , a pet scan showed absence of any metabolically active focal uptake in whole body .\nchemotherapy with vac ( vincristine , actinomycin d , and cyclophosphamide ) alternating with ie ( ifosfamide and etoposide ) for a year was planned .\nsection showing malignant round cells arranged in pattern sheets infiltrating and entrapping the renal glomeruli and tubules { figure 1a : h&e ; 100 , figure 1b : h&e ; 200 } ( a ) the tumor cells express membranous expression of cd99 { dab ; 200 } ( b ) the tumor cells express nuclear positivity for fli-1{dab ; 200 } ( c ) the tumor cells express cytoplasmic positivity for neuron - specific enolase ( nse ) { dab ; 200 } ( d ) the tumor cells expressing cytoplasmic positivity for synaptophysin { dab ; 200 }\nthe primitive neuroectodermal tumor ( pnet ) , was first recognized by arthur purdy stout in 1918 , and is a member of the family of small round - cell tumors . pnet arising in the kidney was first reported by mor in 1994 .\nprimitive neuroectodermal tumors occurs preferentially in the soft - tissues of the paravertebral region and chest wall , less frequently in extremities , with a slight male predominance .\nrpnet appears to be an unique clinical entity that behaves more aggressively than pnet arising at other sites .\nthe presenting symptoms and images of rpnet are non - specific and similar to other renal tumors .\nrpnet show a male predominance with 85% cases being diagnosed during the second to fourth decade .\nit is an aggressive tumor that tends to recur locally and to metastasize to lymph nodes , lung , liver , bone , and bone marrow , which entail a worse prognosis .\nthe differential diagnosis of rpnet includes other small round cell tumors like neuroblastoma , adult nephroblastoma , malignant lymphoma , rhabdoid tumor , small cell carcinoma and monophasic , poorly differentiated , round cell variant of synovial sarcoma , carcinoid , rhabdomyosarcoma , clear cell sarcoma of the kidney , the small cell variant of osteosarcoma , and desmoplastic small round cell tumor .\ngrossly , rpnet are typically very large tumors with about 65% measuring > 10 cm in diameter .\nthey tend to be grayish in color , encapsulated , and contain focal areas of hemorrhage or necrosis .\nmicroscopically , the tumor is composed of sheets of round cells ; individual cells have a round nucleus with a distinct nuclear membrane , fine powdery chromatin , and 1 or 2 small nucleoli .\nthe cytoplasm is ill - defined , scanty , usually pas - positive , and mitosis are variable .\nperivascular pseudo rosettes and homer - wright rosettes are common . to better address the diagnosis ,\nimmunohistochemical markers to be used to confirm diagnosis are cytokeratin ( for nephroblastoma , small cell carcinoma , and synovial sarcoma ) , lca ( for lymphoma ) , nse / chromogranin a ( for neuroblastoma ) , and cd-99 for pnet .\ncd99 ( the product of mic2 gene ) greatly aids in recognizing the es / pnet family of tumors .\nmany pnet also stain for neural markers , including nse , leu-7 , s-100 protein , synaptophysin , and pgp9.5 .\nthe most frequent translocation in pnet is t(11;22)(q24;q12 ) , detected in approximately 90% of cases , resulting in ews - fli fusion gene .\nthe overall survival in patients who had localized rpent was longer than that in the patients who had rpent with regional nodes or distant metastases .\nthe role of radiotherapy is not clear , but it may be advocated in locally advanced disease and involvement of gerota 's fascia .\npost - operative chemotherapy for rpent is usually used and can improve the prognosis of rpnet .\nthe most commonly used chemotherapeutics are adriamycin , etoposide , dactinomycin , vincristine , cyclophosphamide , and ifosfamide . a multimodality management is recommended .", "answer": "primitive neuroectodermal tumor of the kidney is a rare entity . \n very few cases of primary renal pnet have been reported to date . \n most literature about rpnet is isolated case reports . \n we report a case of rpnet in a 39-year - old male with a pre - operative diagnosis of renal cell carcinoma with renal vein thrombosis . \n the patient underwent radical nephrectomy with thrombolectomy , and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells . \n tumor cells were positive for cd 99 and fli-1 , hence confirming the diagnosis of primitive neuroectodermal tumor . \n post - surgery , patient was given vac / ie - based adjuvant chemotherapy . in view of highly aggressive nature of this tumor , \n prompt diagnosis and imparting effective chemotherapy regimen to the patient is required , and it is important to differentiate pnet from other small round - cell tumors because of different therapeutic approach .", "id": 128} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninvasive meningococcal disease ( imd ) is due to infection with the gram - negative bacterium neisseria meningitidis ( n. meningitidis ) .\nalthough fulminant septicemia is less common , it is highly fatal , even if treated .\napproximately 500 000 cases occur worldwide annually , resulting in approximately 50 000 deaths and severe long - term complications in up to 20% of survivors .\ndeafness , intellectual and learning impairment , epilepsy , and other neurological deficits are frequent sequelae that lead to long - term reduction in quality of life . according to the world health organisation ( who ) estimates , the overall notification rate of imd in europe ranges from 0.214 cases per 100 000 in the general population .\nalthough the rates of imd can be low in european and other industrialized countries , the disease is potentially devastating , with a case mortality rate that has remained at about 510% despite treatment . in europe ,\nthe highest numbers of confirmed imd cases are reported in children younger than 5 y of age ( 7.37 per 100 000 ) , followed by children aged 1524 y ( 1.44 per 100 000 ) .\nmost of these cases of imd occur sporadically , although small local outbreaks are not uncommon .\nwhile the majority of imd infections are caused by n. meningitidis serogroups a , b , c , x , w-135 , or y , their relative prevalence has varied considerably over time and by geographical location , making trends in disease epidemiology unpredictable . in europe , the majority of imd cases ( 85% ) are caused by serogroups b and c , while serogroup y is the third most frequently reported cause ( 3% in 2008 , and 4% in 2009 ) .\noverall , the number of cases of imd attributable to serogroup y increased by 42% across european countries between 2007 and 2009 . however , the incidence of n. meningitidis infection due to serogroup c has declined since the introduction of the meningococcal group c conjugate vaccine ( mcc ) in some european countries while the incidence of imd across europe has also changed .\nactive surveillance is crucial to assess the epidemiology and burden of imd , as well as the impact of vaccination . in european countries , in which adequate surveillance systems have been in place for > 10 y\n, long - term surveillance has detected large reductions in meningococcal serogroup c disease following the introduction of the mcc .\nhowever , the scarcity of comprehensive country - specific data on the current burden of meningococcal disease in turkey arises from the lack of homogenous surveillance system , making it difficult to understand and to predict the dynamic changes in serogroup - specific epidemiology .\nmeningococcal conjugate acwy vaccine is used for both individual protection ( e.g. , target groups such as hajj pilgrims , military recruits , or teenagers in the united states ) and mass campaign vaccinations .\nit is established that mcv has a great impact in reducing meningitis if used at large scale , such as the use of menc conjugated vaccine in the uk . while commonly used meningococcal vaccines in europe cover serogroups a , c , y , and w-135 , an effective vaccine against serogroup b has not been available until recently . a quadrivalent protein - based serogroup b vaccine developed by novartis vaccines and diagnostics has been licensed in the eu for infant vaccination . although its use has not been implemented in large - scale vaccination programmes , phase iii studies have demonstrated that the vaccine has the potential to protect against 78% of all imd - causative serogroup b strains .\nlack of systemic surveillance data on serogroup - specific meningococcal epidemiology complicates the decision to be made by health authorities with regard to implementation and choice of available meningococcal vaccines .\nthe purpose of this review is to provide up - to - date information on the epidemiological situation regarding the burden of imd in turkey .\nin turkey , data available on the burden of imd at the national level are based on records collected by the turkish statistical institute ( tsi ) and by the ministry of health .\naccording to ministry of health data , between 1989 and 1999 , the incidence of imd varied between 1 and 35 cases per 100 000 and the mortality rate varied between 0.71 and 2.62 per million cases .\nthe tsi reports that meningococcal infections were responsible for 10.2% ( 1336 ) of all deaths in children under 5 y of age in year 2008 .\ntsi reports 21 , 14 , and 15 deaths from meningococcal infections in all age groups in 2010 , 2011 , and 2012 , respectively based on icd-10 coding system .\nthese contradictory data might be due to either the notification procedure ( report of death due to imd or report of newly identified imd cases ) or the identification of causes .\nthe current situation on meningococcal epidemiology may be better reflected by the prospective multicenter sentinel surveillance for childhood bacterial meningitis conducted by 2 groups since year 2005 .\none of the investigator - initiated sentinel surveillance studies was conducted by ceyhan et al . between february 16 , 2005 , through february 15 , 2006 , for acute bacterial meningitis among children admitted to 12 participating hospitals from 7 geographic areas and 12 health centers in 9 cities .\nthis study reports that n. meningitidis was the leading cause of bacterial meningitis in children aged < 1 y ( 56.5% ) followed by those aged 14 y. among the samples that were positive for n. meningitidis following pcr analysis , serogroup w-135 was the cause of most infections59 ( 42.7% ) cases were due to serogroup w-135 , 43 ( 31.1% ) were due to serogroup b , 3 ( 2.2% ) were due to serogroup y , and 1 ( 0.7% ) was due to serogroup a. there were no cases with a positive result for serogroup c. in this study , serogroup w-135 was also more common in children aged 416 y , while serogroup b was slightly more common in children aged <3 y. n. meningitidis serogroup w-135 was more prominent than the other meningococcal serogroups in the southeast anatolia while n. meningitidis serogroup b was much more common in the marmara ( northwestern turkey ) and the central region . during ongoing surveillance by ceyhan et al . between 20072009 , while the overall imd incidence was stable , the prevalence of imd due to serogroup b was reported to increase to 35% and the prevalence of serogroup w-135 decreased .\ninterestingly , the same group states that during the first 9 mo of 2011 , serogroup w135 was the predominant serogroup , followed by serogroup a , and serogroup b was observed in only 2.5% of cases .\nanother nationwide prospective rt - pcr - based surveillance for childhood bacterial meningitis was conducted between july 2006 and january 2009 and the turkish ministry of health with participation of 37 referral hospitals located in 23 cities in 7 geographic regions of the country .\nrt - pcr detected bacterial dna in 246 ( 29% ) of 841 csf specimens from children with suspected bacterial meningitis , of which 131 ( 53% ) were due to streptococcus pneumoniae , 47 ( 19% ) were due to neisseria meningitidis , and 40 ( 16% ) were due to hemophilus influenzae type b. in this study , 29 ( 62% ) of 47 n. meningitidis isolates were determined as serogroup b , 2 ( 4% ) serogroup c , 1 ( 2% ) serogroup x , 1 ( 2% ) serogroup a , 1 ( 2% ) serogroup w135 , and 13 ( 28% ) other serogroups ( undetermined ) .\nsixteen ( 32% ) of n. meningitidis were detected from the marmara ( north - western turkey ) region and only 5 ( 11% ) from the southeast anatolia .\nto prevent imd among young infants , protection needs to be achieved early in life . since the introduction of the first meningococcal conjugate vaccines in 1999\n, remarkable progress has been made in reducing the morbidity and mortality caused by meningococcal disease .\nstudies have demonstrated that meningococcal c conjugate ( mcc ) vaccination confers protection in infancy ( 012 mo ) from the first dose but this protection is short - term .\nhowever , administration of a booster dose early in the second year of life results in longer protection .\nthe burden of imd is the highest among infants aged < 1 y ( 2.6 cases per 100 000 persons ) in the us . among infants younger than 1 y of age , more than 50% of cases\nit was recently reported that bacterial meningitis was most frequently observed in the first 7 mo of life , regardless of the etiologic agent .\nall meningococcal meningitis cases occurred in those < 6 mo of age and mostly in those <3 mo of age .\nall cases in the youngest infants were due to meningococcal serogroup b and w135 in turkey .\nif meningococcal vaccines against men b and serogroups a , c , w135 , y with early infant indications may also be registered , we would have an opportunity to protect young infants starting from 2 mo of age in turkey .\nthe growing - complexity of national immunization programme ( nip ) in turkey has resulted in as many as 4 required injections during a single healthy baby visit .\nthe number of injections in a well - baby visit in the us is up to 7 .\nprotecting against vaccine preventable meningococcal serogroups will result in an increase in the number of injections up to 6 in turkey , but this is acceptable when we compare with developed countries ( table 1 ) current nip schedule .\ncontrasting data obtained from different surveillance studies may be related to regional differences in the weight of subjects enrolled from different regions of the country or methods used .\nargues that higher rates of serogroup w-135 since 2005 in their earlier study is due to 100 000 turkish hajj pilgrims traveling to saudi arabia every year , which was also seen in malaysia and singapore .\nthe results reported by bakir et al . showing the predominance of serogroup b may be explained by the millions of the turkish diaspora living in europe , where serogroup b is predominant , who travel back and forth to the country many times annually .\nthis is a more likely explanation of the existing sero - epidemiology because other explanations of the sharp decrease of serogroup b imd from 35% down to 2.5% in only a few years in the absence of serogroup - specific vaccination are unlikely .\nthis variation may also reflect the introduction and implementation of detection techniques such as the pcr .\nsero - epidemiology data on imd in 2 different surveillance studies in turkey at the same time periods had different results .\nthis complicates the decision to be made by health authorities on the implementation and the type of meningococcal vaccine to be chosen . in the light of available surveillance data in turkey , a vaccine effective against meningococcus serogroup b as well as serogroup\nsystematic continuous surveillance is warranted to measure the urgency of need and effectiveness of a vaccination program for imd . the who recommends the introduction of appropriate large - scale meningococcal vaccination programmes in countries with high ( > 10 cases/100 000 population / year ) or intermediate ( 210 cases/100 000\npopulation / year ) imd incidence rates , and in countries with frequent epidemics . in countries with lower imd incidence rates ( < 2 cases/100 000 population / year ) , vaccination is recommended for defined risk groups , including children and young adults residing in close communities , laboratory workers at risk of exposure , travelers to high - endemic areas and immunodeficient individuals .\noverall , each country should choose the appropriate vaccination program depending on the locally prevalent serogroup of n. meningitidis .\nconjugate vaccines are preferred over polysaccharide vaccines due to their potential for herd protection , immunologic memory and their increased immunogenicity , particularly in children < 2 y of age .", "answer": "each country chooses the appropriate vaccine against imd depending on the locally prevalent serogroups of n. meningitides . \n frequency of each meningococcal serogroup varies considerably over time and by geographical location . despite the majority of imd cases ( 85% ) \n are caused by serogroups b and c in europe , true prevalence of serogroup b imd cases in turkey is unclear . in one of the recent studies , the sharp decrease of serogroup b imd from 35% down to 2.5% in a few years despite the absence of vaccination is confusing . \n millions of european turkish people travels from europe to turkey every year who could most probably carry serogroup b. it is obvious that a nationwide active surveillance is crucial to assess the the true epidemiology and burden of imd which has a major impact on the choice of vaccine type and age interval the vaccination to be implemented .", "id": 129} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntuberculosis ( tb ) is a contagious , infectious disease , due to mycobacterium tuberculosis ( mt ) , which usually lasts throughout the life course and determines the formation of tubercles in different parts of the body .\nmt has very ancient origins : it has survived over 70,000 years and it currently infects nearly 2 billion people worldwide ; with around 10.4 million new cases of tb each year , almost one third of the world 's population are carriers of the tb bacillus and are at risk for developing active disease .\ntb has always been associated with a high mortality rate over the centuries , and also nowadays , it is estimated to be responsible for 1.4 million tb deaths , among infectious diseases after human immunodeficiency virus ( hiv ) .\ndue to its infectious nature , complex immunological response , chronic progression and the need for long - term treatment , tb has always been a major health burden ; in more recent years , the appearance of multi - drug resistant forms and the current tb - hiv epidemic , associated with its severe social implications , treating and preventing tb have represented a permanent challenge over the course of human history [ 4 , 5 ] .\nit has been hypothesized that the genus mycobacterium originated more than 150 million years ago .\nmycobacterium ulcerans , causing infections since ancient times , requires specific environmental conditions as reflected nowadays in its distribution worldwide .\nthree million years ago , an early progenitor of mt might have infected early hominids in east africa and 20.000 - 15.000 years ago , for the first time , the common ancestor of modern strains of mt might have appeared [ 8 , 9 ] .\negyptian mummies , dating back to 2400 bc , reveal skeletal deformities typical of tuberculosis ; characteristic pott 's lesions are reported and similar abnormalities are clearly illustrated in early egyptian art [ 10 , 11 ] .\nthe first written documents describing tb , dating back to 3300 and 2300 years ago , were found in india and in china respectively [ 12 , 13 ] .\nthe ancient hebrew word schachepheth is used in the biblical books of deuteronomy and leviticus in order to describe tb ; in the same period , in the andean region , archeological evidence of early tb , including pott 's deformities , was provided by peruvian mummies , suggesting that the disease was present even before the colonization of the first european pioneers in south america [ 15 - 18 ] . in the ancient greece tb\nhippocrates described phtisis as a fatal disease especially for young adults , accurately defining its symptoms and the characteristic tubercular lung lesions .\nexcellent discoveries of the early scientists who studied tb were made in the same period : in greece , isocrates was the first author supposing that tb was an infectious disease , while aristotle suggested the contagious nature of \" king 's evil \" in pigs and oxes . in roman times ,\ntb is mentioned by celso , aretaeus of cappadocia and caelius aurelianus , but it is not recognized as sharing the same etiology of extrapulmonary manifestations such as scrofula , pott 's disease and tb lupus . according to the greek clarissimus galen , who became personal physician of the roman emperor marcus aurelius in 174 ad , the symptoms of tb include fever , sweating , coughing and blood stained sputum ; he recommended fresh air , milk and sea voyages as successful treatments for the disease [ 20 - 22 ] .\nafter the decline of the roman empire , tb was widespread in europe in the viii and xix centuries , as witnessed by several archaeological findings .\nthe byzantine doctors aetius of amida , alexander of tralles and paul of aegina described the pulmonary and glandular forms of tb , while in the arabic empire , avicenna supposed the contagious nature of tb .\nin the middle ages , scrofula , a disease affecting cervical lymph nodes , was described as a new clinical form of tb .\nthe illness was known in england and france as \" king 's evil \" , and it was widely believed that persons affected could heal after a royal touch . in the 12 century , william of malmesbury reported complementary treatments including visits at royal tombs , the kings ' touch or the use of a coin - talisman .\nthe practice of the king 's touch established by english and french kings continued for several years .\nqueen anne was the last english monarch to use this practice ( 1712 ) , george i put an end to it in 1714 , while in france it continued up to 1825 . in the middle ages , moreover , the french surgeon guy de\nchauliac ( 1363 ) for the first time proposed a healing intervention for the cure of the \" king 's evil \" .\nguy de chauliac was also strongly in favour of the removal of scrofulous gland with an engraving , as recommended by paul of aegina , who advised the surgical removal of the diseased gland , taking care not to harm vessels or nerves of which the neck region is rich .\nas far as concerns the contagious nature of tb , a clear definition was first given by girolamo fracastoro in the sixteenth century .\nthe exact pathological and anatomical description of the disease was illustrated in 1679 by francis sylvius , in his work opera medica , in which he describes tubercles , their progression to abscesses , cavities and empyema in the lungs and in other sites of consumptive patients .\nshort afterwards , in italian health law , in particular in an edict issued by the republic of lucca in 1699 , there is the first official reference to the infectious nature of the disease . in 1735\nthe health board of the republic ordered the compulsory notification and isolation of consumptives , forbidding their admission in public hospitals , and establishing specific places for their treatment .\nin 1720 , for the first time , the infectious origin of tb was conjectured by the english physician benjamin marten , in his publication \" a new theory of consumption \" . for the early eighteenth century\nboth terms consumption and phthisis were used in the 17 and 18 centuries , until in the mid-19 century johann lukas schnlein coined the term \" tuberculosis \" . in the 18 century in western europe , tb had become epidemic with a mortality rate as high as 900 deaths per 100,000 inhabitants per year , more elevated among young people . for this reason ,\ntb was also called \" the robber of youth \" . during the industrial revolution , the diffusion of particularly problematic social conditions , such as extremely deprived work settings , poorly ventilated and overcrowded housing , primitive sanitation , malnutrition and other risk factors ,\nup to a third of english tradesmen and employees died of tb , whereas the same proportion decreased to a sixth in the upper class .\nthe extreme anemic pallor of people affected by tb was at the origin of the new term \" white plague \" , coined during the 18 century [ 20 , 35 ] .\none hundred years later , tb was defined as \" captain of all these men of death \" because of its epidemic proportions in europe and north america , determining one in four deaths . at the beginning of the 19 century\n, there was a large scientific debate about different theories concerning the etiopathological origin of phthisis , arguing whether it might be considered : an infectious disease as generally considered in southern europe an hereditary one as stated in northern europe or a form of cancer .\non the other hand , the discussion was about scrofula , tubercles , and phthisis as separate disease entities or manifestations of the same illness . in 1793 , the caseous necrosis , \" cheese - like \" , phthisic abscesses were named \" tubercles \" by the scottish pathologist matthew baille . in 1810 , the french physician gaspard - laurent bayle of vernet described the disseminated \" miliary \" tb in his work recerches sur la phthisie pulmonaire , recognizing tb not only as a disease affecting the lung , but a generalized one , clinically defined by coughing , difficulty in breathing , fever and purulent expectoration [ 37 , 38 ] . in 1819 ,\nthe french theophile laennac identified the presence of consolidation , pleurisy and pulmonary cavitation as pathognomonic signs of pulmonary or extrapulmonary tb .\ntuberculosis most commonly affects the respiratory tract , but it could also infect gastrointestinal , bones , joints , nervous systems , lymph nodes , genitourinary tract and skin with inflammatory infiltration , caseation , necrosis , abscesses , fibrosis , formation of tubercles and calcification [ 39 , 40 ] .\nhe described their first appearance in the lungs , in their \" miliary \" ( \" millet seed - like \" ) form , their progressing to larger tubercles containing \" cheese - like \" ( \" caseous \" ) material , their breakdown into pus , and eventually forming cavities and empyema .\nextra - pulmonary phthisic tubercles were recognized in the intestines , liver , meninges and other organs , as also described by sir percivall pott , a british surgeon that in 1779 defined as \" pott 's disease \" the vertebral collapse and spinal cord paralysis caused by tb infection [ 33 , 36 , 37 , 41 , 42 ] . in 1843 , the german physician philipp friedrich hermann klencke succeeded in the experimental reproduction of human and bovine forms of tb , causing generalized tb in rabbits , through a successful inoculation of material from a miliary tubercle into their liver and lungs . in 1849 lebert , publishing his work traite pratique des maladies scrofuleuses et tuberculeuses , suggested that the \" king 's evil \" was a childhood disease that might cause suppuration and ulceration of different body 's sites such as skin , ears , eyes , joints , bones , with a different pathogenesis from tb .\nthe first successful remedy against tb was the introduction of the sanatorium cure , described for the first time in 1854 in the doctoral dissertation \" tuberculosis is a curable disease \" by hermann brehmer , a botany student suffering himself from tb , who reported his healing after a travel to the himalayan mountains .\nafterwards brehmer founded an institution in gorbersdorf , a mountain town situated in a fir forest , in order to cure patients with continuous fresh air and good nutrition .\nthe subsequent sanatoria were built with the same setup and permitted to cure a lot of tb patients in the next decades .\nthe infectious nature of tb was demonstrated in 1865 by jean - antoine villemin , a french military surgeon at the army medical school .\nhe formulated his hypothesis observing that tb was more frequent among soldiers who stationed for long times in barracks than among those in the field .\nhe also highlighted how healthy army recruits coming from the countryside often became consumptive some months after the beginning of their service .\nvillemin 's experiments consisted in inoculating a rabbit with \" a small amount of purulent liquid from a tuberculous cavity \" removed at autopsy from an individual died of tb .\nas described in villemin 's work cause et nature de la tuberculose : son inoculation de l'homme au lapin , the inoculated animal remained alive and no disease signs were discovered , but at autopsy , three months later , extensive tb was evident .\nvillemin suggested that phthisis could be similar to glanders , an infectious disease in horses [ 20 , 34 , 36 , 37 , 47 ] .\npreuves rationelles et exprimentales de sa spcificit et de son inoculabilit , dated 1868 , in which he stated the presence of tblike illnesses in different animals .\nthe author also noticed that more crowded urban areas had a higher prevalence of tb and that some parts of the world , like new zealand and australia , seemed to have not known tb until the arrival of pioneers .\nsome years later , in 1867 , theodor albrecht edwin klebs was one of the early scientists to try to isolate the tb bacillus , sowing tuberculous material on egg white , stored in sterile flasks . in his experiments , the culture was quickly muddy and it was possible to recognize mobile bacilli , which , after inoculation into the peritoneal cavity , caused the disease in guinea pigs .\nusing the methylene blue staining recommended by paul ehrlich , he identified , isolated and cultivated the bacillus in animal serum .\nrobert koch presented this extraordinary result to the society of physiology in berlin on 24 march 1882 , determining a milestone in the fight against tb . in the decades following this discovery , the pirquet and mantoux tuberculin skin tests ,\nalbert calmette and camille gurin ( bcg ) vaccine , selman waksman streptomycin and other anti - tuberculous drugs were developed .\nkoch contributed also to the elucidation of the infectious etiology of tb and for his scientific results , he was awarded the nobel prize in medicine in 1905 [ 33 , 51 ] .\nnowadays tb is still a major public health problem , for this reason a combined strategy , based on improving drug treatment , diagnostic instruments , and prevention strategy , is necessary , in order to eradicate m. tuberculosis by the year 2050 , as committed by the world health organization ( who ) .", "answer": "summarytuberculosis ( tb ) is a contagious , infectious disease , due to mycobacterium tuberculosis ( mt ) that has always been a permanent challenge over the course of human history , because of its severe social implications . \n it has been hypothesized that the genus mycobacterium originated more than 150 million years ago . in the middle ages , scrofula , \n a disease affecting cervical lymph nodes , was described as a new clinical form of tb . \n the illness was known in england and france as \" king 's evil \" , and it was widely believed that persons affected could heal after a royal touch . in 1720 , for the first time , the infectious origin of tb was conjectured by the english physician benjamin marten , while the first successful remedy against tb was the introduction of the sanatorium cure . \n the famous scientist robert koch was able to isolate the tubercle bacillus and presented this extraordinary result to the society of physiology in berlin on 24 march 1882 . in the decades following this discovery , the pirquet and mantoux tuberculin skin tests , albert calmette and camille gurin bcg vaccine , \n selman waksman streptomycin and other anti - tuberculous drugs were developed .", "id": 130} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncharging of grains of identical insulating \n materials during collisions \n has been of considerable interest recently , both for its intrinsic \n physics and for its applications to situations ranging from volcanic \n dust plumes and desert sandstorms to industrial powder processing .\nhowever , work up to now has not explained why in some instances \n charging grows , rather than diminishes as one might naively expect , \n and can run away extremely rapidly , leading to electrical discharges : \n lightning .\noutstanding examples of runaway collisional charging involve \n ice , in thunderstorms both on earth and \n on other planets , and , it is speculated , in the \n solar nebula ; these instances concern granular media whose particles \n also undergo nucleation , growth , and fission , so that they , in effect , \n reproduce . in this work ,\nwe demonstrate with a minimal dynamical model \n that secondary nucleation , production of a new particle from an existing \n particle , is a key process in producing runaway electrical charging \n in self - replicating granular matter .\nwe concomitantly present the \n results of experiments on growing ice in situ from the vapor phase \n within an environmental scanning electron microscope .\nwe show that \n an effect of the electric field is to induce the formation of fast - growing \n ice palms \nintermediate in morphology between whiskers \n and dendrites ; the ease of breakage of these palmlike formations will \n clearly favor secondary nucleation and hence runaway electrification . in a thousand seconds , more or less , its volume increases \n a thousandfold , the intensity of its electric fields increases a thousandfold , \n and its electric energy increases a billionfold ; thus described \n vonnegut the tremendous metamorphosis a cumulus cloud undergoes to \n become a cumulonimbus or thundercloud .\nthundercloud electrification is a consequence of ice particles colliding \n within a cloud and exchanging electrical charge .\ncharge dipole development \n in a thunderstorm is due to the physical separation of particles with \n opposite charges inside the cloud : larger , heavier particles will \n fall , while smaller , lighter particles will rise in the updraft , owing \n to their different dynamics , and these \n particles carry different charges .\nusually , \n in thunderstorms , the smaller ice particle is an ice crystal and carries \n positive charge aloft in the updraft ; the larger graupel ice particle \n falls with an opposite negative charge , leading to a typical thunderstorm . \n\nwe may contrast the foregoing with charging in other granular media , where it has been argued that simple geometry , without growth and \n fission processes , leads to a net transfer of electrons from larger \n to smaller particles , so that smaller \n particles tend to charge negatively and larger ones positively . whether \n this differential charging tendency operates one way or the other \n depends on the microphysics , which differs for different materials , \n so this polarity differs .\nfor our present purposes , however , what \n is relevant is that there should exist such a triboelectric charging \n tendency in one sense or the other .\nhere we build a minimal model \n ( figure 1 ) incorporating solely the collisional \n dynamics of charge transfer plus nucleation , growth , and fission processes , \n which we aim to have general relevance to self - replicating granular \n media .\nanatomy of our minimal model of charging of friable self - replicating \n granular matter through secondary nucleation , incorporating the processes \n of particle growth ( ri ri + 1 ) , advection \n ( with speed ui ) , collision , \n charge transfer , and fission ( with probability s ) .\nwe consider ( figure 1 ) a one - dimensional \n system of length l , within which we place randomly n neutrally charged particles , qi = 0 for i = 1 , ... , n , of size ri extracted \n from a gaussian distribution of sizes with mean r = 1 and standard deviation . these particles grow at a constant \n rate , independent of particle size , that sets the time scale of the \n problem . at the same time , they sediment in an upward flow of constant \n magnitude at their terminal velocity , ui , determined by the instantaneous balance of fluid \n drag and gravitational forces .\nthe sedimentation speed is normalized \n by the updraft speed ( i.e. , ui = 1 for passive tracers ) and is approximated by a linear function \n of the particle size ri , ui = 1 ( ri / rc ) .\nthis function is positive ( negative ) for ri below ( above ) a critical value rc .\nthe sedimentation speed of all particles in the simulation \n is updated every integration time step ; in this way , small particles \n that are initially advected upward by the updraft slow their upward \n motion as they grow and begin moving downward after reaching the threshold rc . when the trajectories of two particles i and j cross , they collide . to overcome \n the 1d limitation of \n the model ,\nwe allow particles to get past one another after the collision , \n so that after each time step particles end up in whatever final position \n their velocities prescribe .\nboth mass and charge are conserved during \n a collision but , while charge is transferred in every collision ( the \n smaller particle leaving the collision positively charged : qi qi + 1 and qj qj 1 with ri < rj ) ,\nwe assign \n a certain probability s for fission to occur for \n each of the two particles involved in a collision .\nif fission does \n occur for particle i , a new , neutrally charged particle \n with radius 1 splits from it , reducing its size to ri = ri 1 .\nalthough fracture of particles has been shown \n to lead to additional charging , we left \n this effect out of the model for the sake of simplicity as it does \n not change qualitatively the presented results .\nboundary conditions \n are absorbing : particles leaving the system \n through the upper or lower boundary are absorbed there , and do not \n participate further in the dynamics , but their charge accumulates \n to the total charge at the boundaries : qu(l ) = qi for i leaving the system through the upper ( lower ) boundary , \n respectively .\nthe total large - scale charge separation is calculated \n as q = qu ql . for given initial conditions ( set completely \n by the concentration \n of particles , \n= n / l , and \n the initial spread of the size distribution , ) , the behavior \n of our minimal model then depends on just two parameters , the critical \n radius rc and the secondary nucleation \n rate s. in what follows , we set rc = 8 , = 2 and = 0.1 and explore the behavior \n of the model with respect to the secondary nucleation rate s. we note that electric forces are not considered in the \n model but implicitly ( through the secondary nucleation rate responsible \n for the process of fission ) .\nfigure 2 displays the typical transient \n dynamics of the charge distribution in the model .\nthe figure shows \n an initial stage in the transient dynamics chosen to exemplify how \n the charge separation process operates in the model .\nas time passes , \n as indicated by black arrows , light positively charged particles move \n toward the upper boundary while heavy negatively charged ones move \n in the opposite direction , contributing to a non - negligible dipolar \n large scale charge separation q .\nregions where \n localized collisions are produced generate large charges that are \n then separated by differential advection . even at those early stages \n in the process , the global dipolar structure of the system , quantified \n by the large - scale charge difference between the boundaries q , is the dominant field .\nfigure 3 shows particle size and charge distributions for the upper and lower \n boundaries .\nas time passes , light positively charged particles move toward the \n upper boundary while heavy negatively charged ones move in the opposite \n direction , as indicated by arrows , contributing to a non - negligible \n large - scale dipolar charge distribution q . \n\nparticle size ( rj ) \n and charge ( qj ) distributions \n for the system upper boundary ( left panels ) and lower boundary ( right \n panels ) .\nthe total charge separation \n q at a finite time step ( which is a measure \n of the speed of the charge - separation process ) displays nonmonotonic \n discontinuous behavior as a function of the secondary nucleation rate s. below a critical value sc , the long - term dynamics reaches an emptying state with no particles \n left in the domain and a finite ( and small ) final charge separation ; \n as there are few secondary nuclei , the initial particles grow and \n collide very little before leaving the system .\noccasionally some charge \n is produced , but not much . above sc , the \n number of collisions grows , and with it the charge transfer .\nas the \n charge acquired by the particles is correlated with their size , charge \n separation occurs too .\nthe system approaches a steady state with an \n average nonzero number of particles in the domain and an exponentially \n divergent charge separation , as shown in the inset of figure 4 .\nthis exponential charge growth is limited in nature \n by electrical discharges , lightning .\nthe total charge separation q displays nonmonotonic \n behavior as a function of the secondary nucleation rate s. inset : time evolution of q for s = 0.1 shows the exponential growth characteristic of all \n values of s > sc .\nhowever , for secondary - nucleation \n rates much greater than sc , there are \n more and more collisions .\nthe particles \n undergo more fission into secondary nuclei , and although much charge \n is produced , it does not separate as well ; charge separation is still \n exponentially divergent , but the growth rate decreases beyond sc .\nthere is thus an intermediate optimal value \n of the secondary nucleation rate to produce the greatest charge separation . \n\nthis critical value sc 1/(rc ) is 0.0625 in the simulations ( dashed line \n in figure 4 ) .\na smaller value of rc ( which means a weaker updraft ) requires secondary nucleation \n to occur more often ( larger sc ) in order \n to ensure some particles are advected upward ( leading to charge separation ) , \n while the initial density of particles , , controls the collision \n probability .\nit is worth mentioning that even in the limit of very \n high particle density , in which many collisions occur at early \n stages , charge separation is minimal in the absence of secondary nucleation . \n\nearlier work \n of ours made us suspect that secondary nucleation \n ought to be important in runaway collisional charging .\npreviously \n we have shown that the nonlinear feedback effects of secondary nucleation \n are responsible for chiral symmetry breaking in experiments involving \n crystallizing a chiral chemical compound from solution .\nwe showed that secondary nuclei in such stirred crystallization \n experiments are often easily detached whisker or needle crystallites \n growing from a mother crystal , and a runaway process involving the \n formation of secondary nuclei leads to complete chiral symmetry breaking .\nwater molecules possess a high electric polarizability ; they are \n electrical dipoles and can be highly affected by the presence of an \n external field . during dendrite growth , an electric field can produce \n an ordering of the molecular dipoles and increase the molecular flow \n toward the dendrite tip .\nthis increases the growth velocity , decreases \n the tip radius and disables the generation of side - branches , producing \n long whiskers .\nthese effects have long been noted and were studied quantitatively by libbrecht and tanusheva , who measured the tip velocity and found that \n high voltages could multiply the growth rate more than 10-fold .\nwe hypothesized that this dendrite growth mechanism should be involved \n in promoting secondary nucleation .\nthus , we undertook laboratory experiments \n to see whether similarly easily detached forms as in solution crystallization \n experiments are produced in ice under the influence of an electric \n field .\nwe employed a fei quanta 200 environmental scanning electron \n microscope ( esem ) equipped with a liquid nitrogen cold stage to grow \n ice in situ at low pressures and at temperatures of 90200 \n k. the microscope was set up so that the cold finger , together with \n a thermostat , was directly beneath the substrate ( a silicon wafer \n attached with silver glue ) .\nwe began by evacuating the chamber in \n the high - vacuum mode of the microscope ( 6 10 pa ) and lowering the substrate to the working temperature .\nwe first \n scanned the uncovered sample substrate , on which we grew an ice film \n by switching to low - vacuum mode and opening the water input microvalve \n at a pressure of 40 pa for some seconds .\nwe found this was the highest \n pressure at which we could obtain clear images .\nwe closed the microvalve \n at or before the point when the substrate temperature increases and \n can not be maintained at the working temperature , following which we \n switched back to high - vacuum mode and observed the ice growth in situ . in the electron - microscope chamber ,\na high - voltage electron beam \n is used for imaging , and as we display in figure 5 , we find that the electric field produces rapid dendrite \n growth wherever we charge with electrons by imaging .\na typical ice \n morphology seen under these circumstances is of a form intermediate \n between whiskers and dendrites , which often takes on the aspect of \n a palm tree ; see figure 5a . as we zoom out \n ( figure 5b , c )\n, we note that the palm forest \n is found only where we had been imaging ; outside the area of the electron \n beam , we find a relatively flat film of ice , while within the imaged \n zones , three in figure 5c , we find faster ice \n growth and the ice forest .\ngrowth in an \n esem : ( a , b ) at t = 170 k , p = 40 \n pa , v = 30 kv , an ice \nthe forest displays the morphology intermediate between whiskers \n and dendrites typically formed with charged ice .\n( c ) in an overview , \n the three zones where we imaged and charged with electrons stand out , \n showing the increased growth on the background ice film .\nwe had noted such palmlike forms in previous experiments \n involving \n growing ice inside an electron microscope , but had not then realized that the electric field was involved in \n their production .\nthese experiments are necessarily qualititative , \n being performed within the chamber of an unmodified esem , but we find \n the results suggestive : owing to their geometry , the breakage of these \n structures on collision is likely and will lead to the formation of \n new nucleation centers .\nsuch friable morphologies do not only form \n in ice under electric fields ; snowflakes too have such delicate structures , \n but an electric field promotes this form of growth .\nour minimal physical model of a self - replicating \n granular material \n shows how secondary nuclei from such growth can lead to runaway charging\n. \n these effects may be present in ice on earth , in terrestrial thunderstorms , and in astrophysical ices , in the solar nebula , and in thunderstorms on other planets , some of which , \n for example , on venus , may involve self - replicating granular materials \n other than water ice . it is conceivable that this dynamics is involved \n in the formation of the martian geological structures called razorbacks . while ice is clearly \n the most quotidian example of a friable self - replicating granular \n material , one that breaks easily and continues to grow , other such \n materials can be both sought in different astrophysical environments , \n and also produced in technological contexts .", "answer": "we \n establish that the nonlinear dynamics of collisions between \n particles favors the charging of an insulating , friable , self - replicating \n granular material that undergoes nucleation , growth , and fission processes ; \n we demonstrate with a minimal dynamical model that secondary nucleation \n produces a positive feedback in an electrification mechanism that \n leads to runaway charging . we discuss ice as an example of such a \n self - replicating granular material : we confirm with laboratory experiments \n in which we grow ice from the vapor phase in situ within an environmental \n scanning electron microscope that charging causes fast - growing and \n easily breakable palmlike structures to form , which when broken off \n may form secondary nuclei . \n we propose that thunderstorms , both terrestrial \n and on other planets , and lightning in the solar nebula are instances \n of such runaway charging arising from this nonlinear dynamics in self - replicating \n granular matter .", "id": 131} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe majority of women with menorrhagia , postcoital bleeding , intermenstrual bleeding , or postmenopausal bleeding ultimately undergo diagnostic hysteroscopy with endometrial sampling as part of their assessment , particularly if symptoms persist or pelvic imaging suggests a uterine abnormality .\ndilatation and curettage ( d&c ) has been widely considered to be the method of choice for obtaining endometrial samples for histopathological evaluation\n. however , the needs for admission and general anesthesia and their associated costs have made this option less favorable . in the outpatient setting , endometrial sampling is an effective and acceptable method for obtaining endometrial samples for histopathological assessment [ 3 , 4 ] .\ninadequate sampling is more problematic in postmenopausal women , for whom up to 68% of endometrial samples are reported to be inadequate . in our institution , the only sampling tool available to perform the outpatient sampling procedure is the uterine explora model i - mx120 ( http://www.coopersurgical.com/ ) ( figure 1 ) .\nin addition , the device is sterile and disposable ( one - time use ) .\nthe advantages of using explora rather than d&c as a sampling device include a reduction in hospitalization costs , extra convenience for the patient and physician , and the minimal complications of the procedure .\nthe purpose of this study is to compare the effectiveness of the explora model i tool with the conventional d&c technique for obtaining adequate endometrial samples that are capable of providing specific and informative histopathologic diagnoses .\nafter obtaining the approval of our institutional review board , all endometrial samples received at the histopathology department in king khalid university hospital ( kkuh , riyadh , ksa ) between january 2007 and december 2010 were included in this study . a total of 1270 endometrial samples were included ( table 1 ) .\ntwo hundred seventy - four samples ( 21.6% ) were obtained by conventional d&c in the surgical theater , while the remaining 996 samples ( 78.4% ) were obtained by senior obstetrics and gynecology residents who used a standardized biopsy technique in the outpatient procedure rooms . during the usage of the explora model\ni , the syringe provided with the instrument was used to create a negative pressure , and the explora was rotated as it was withdrawn . after withdrawal , the tip was cut off , and the tissue was placed in 10% buffered formalin saline fixative and was sent for pathological examination .\nthe pathologists who interpreted the endometrial samples were blinded to the instrument or method used to obtain the samples .\nan inadequate sample was defined as consisting of only blood , cervical mucus , endocervical epithelium , or blood with fragments of endometrial glands or stroma insufficient for histopathological assessment and diagnosis .\nthe age , gravidity , parity , menstrual history , uterine size , hysteroscopy findings ( when available ) , and the presence or absence of any cervical abnormality were recorded on the request forms , which were reviewed by the investigators . for each of the two methods used ( explora model i and d&c ) , the numbers and percentages of inadequate samples and age group clustering were calculated and statistically analyzed .\nof the 1270 endometrial samples obtained , 253 samples ( 19.9% ) were scored as inadequate . of these samples ,\nthe explora sampler was used to collect 224 samples ( 88.5% ) , whereas 29 samples ( 11.5% ) were obtained by d&c ( figure 2 ) .\nthus , the insufficient tissue percentage was higher with the explora ( 17.6% ) than with d&c ( 2.2% ) , which was a statistically significant difference ( p < 0.0001 )\n. age group clustering ( i.e. , numbers of premenopausal and postmenopausal women ) of inadequate sample results was also calculated ( figure 3 ) . of the 253 inadequate samples ,\n82.6% were from women 45 years of age and older ( i.e. , postmenopausal ) compared to 17.4% in premenopausal women ; the age difference was significant ( p < 0.0001 ) .\nthe detection rates of endometrial hyperplasia and carcinoma using both methods were assessed and calculated .\nof the 73 samples with a diagnosis of endometrial hyperplasia , 50 ( 68.5% ) were diagnosed by d&c , and 23 ( 31.5% ) were diagnosed using the explora sampler .\nhowever , of the 18 samples with a diagnosis of endometrial cancer , the rates of detection were similar between the two methods .\nendometrial sampling for the evaluation of dysfunctional uterine bleeding and the diagnosis of endometrial hyperplasia and carcinoma and other indications remains one of the most commonly performed gynecological procedures [ 14 ] . in recent years\n, less hazardous and more inexpensive and convenient outpatient sampling methods have replaced the traditional , in - hospital , endometrial curettage .\nthe advantages of outpatient endometrial biopsy include reduced cost and less risk for the patient , as no anesthesia is required .\nfurthermore , the discomfort and pain produced by sampling have been reported to be minimal .\nhowever , it is essential to ensure that outpatient endometrial sampling is quantitatively adequate and comparably accurate to conventional dilatation and curettage .\na sample is judged as adequate if a specific diagnosis can be given from the histological examination of the endometrial fragments obtained .\nadequacy can be measured by comparison of either outpatient biopsy with curettage histological evaluation or outpatient biopsy with the results of pathological examination of hysterectomy specimens [ 3 , 4 ] .\nmany techniques for obtaining an endometrial sample without the need for curettage have been described in the literature .\nchicago , il , usa ) and the novak biopsy curette with a 10 ml syringe functioning as an aspiratory device , which have been shown to be equally effective compared to d&c in detecting an endometrial pathology [ 69 ] .\nhowever , the vabra aspirator and novak biopsy curette , although widely available and relatively inexpensive , have several disadvantages , including the need for an electric vacuum pump to perform the aspiration in the former technique and the pain caused by both methods . as a result of these drawbacks , smaller inexpensive and\nself - contained instruments have been developed and the prototype of this class of endometrial samplers is the pipelle . the pipelle has been shown to have a diagnostic accuracy comparable to that of vabra aspiration and the novak curettage while causing less pain [ 911 ] .\nall of these instruments ( i.e. , the vabra aspirator , the novak biopsy curette , and the pipelle ) have low rates of false - negative and insufficient tissue results for the detection of endometrial abnormalities , as determined by comparison to hysterectomy specimens [ 1113 ] .\nit was found that pipelle biopsy had a sensitivity of 99.2% in pinpointing high grade cancer and a sensitivity of 93% in detecting low grade malignancies ; the sensitivities defined for d&c were 100% and 97% , respectively . while \nexcellent agreement was generally noted between preoperative histology and grade and the final pathology , pre - operative endometrial sampling more commonly provided underestimates of final grade ( low grade versus high grade ) than overestimates .\nthe explora is somewhat similar in its design to the pipelle , but clinical studies on its effectiveness are scarce , with the effectiveness ranging between 14.6 and 15% according to various studies [ 6 , 15 ] .\nour own findings revealed that the rate of obtaining inadequate samples using the explora was much higher ( 17.6% ) than the rates reported in the literature .\nhowever , most of these cases ( 82.6% ) were obtained from postmenopausal women with atrophic endometrial status .\nthis finding is in keeping with the rates reported by other investigators [ 58 , 16 ] .\nthis retrospective study suggests that traditional d&c produces better endometrial sample adequacy than the explora technique .\nthis finding indicates that clinicians performing endometrial sampling would benefit from more experience and training using the explora technique .\nadditional studies comparing the adequacy of samples obtained with different endometrial sampling techniques and devices are warranted .\nfurthermore , we recommend using the d&c procedure when the explora - obtained samples are inconclusive or when the use of the explora sampler is accompanied by ultrasound findings that are suspicious of endometrial hyperplasia or carcinoma .", "answer": "aims . our aim is to compare the adequacy and diagnostic yield of samples obtained by the endometrial explora sampler i - mx120 with endometrial specimens obtained by conventional dilatation and curettage ( d&c ) \n . methods . a total of 1270 endometrial samples \n were received in the histopathology laboratories at the king khalid university hospital , riyadh , saudi arabia , between 2007 and 2010 . in the outpatient clinic , \n the uterine explora model i was used to obtain 996 samples . \n the remaining 274 samples were obtained by conventional d&c . \n sample adequacy and the clustering of inadequate specimens according to age groups by the two different techniques were compared and statistically analyzed . results . out of 1270 endometrial samples , 253 ( 19.9% ) were inadequate . \n the uterine explora was used in 88.5% of these inadequate samples ( 253 samples ) , and the remaining 11.5% were obtained by d&c . \n the insufficient tissue incidence was higher with the explora ( 17.6% ) than with the d&c ( 2.2% ) and the difference was statistically significant ( p < 0.0001 ) . \n the ages of the patients , as well as the clinical indications for the procedures , were recorded . conclusion . \n this retrospective study demonstrated better specimen adequacy when d&c was used compared to the higher rate of sample insufficiency obtained with the explora .", "id": 132} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmedulloblastoma is the most common pediatric brain tumor , with an incidence of ~0.5/100,000 children < 15 years old ( 1 ) .\nit is classified as grade iv according to the world health organization ( who ) ( 2 ) .\ncurrent treatment consisting of surgery , radiotherapy and adjuvant chemotherapy has a limited role in improving the prognosis of patients ( 3,4 ) . novel therapeutic methods based on the specific mechanism of medulloblastoma carcinogenesis\nan increasing number of studies have revealed that micrornas ( mirnas / mirs ) serve a role in tumorigenesis ( 59 ) .\ngene expression is regulated by thousands of known mirnas , which bind to imperfect complementary sites within the 3 untranslated regions of their target protein - coding mrnas , and repressing the expression of these genes at the level of mrna stability and translation ( 10 ) .\nprevious research has revealed that mirnas are involved in the regulation of the majority of physiological and pathological process , including development , life span , and metabolism , and their dysregulation contributes to a number of types of disease , notably cancer ( 11 ) .\nthese small rnas may function as oncogenes or tumor suppressors by modulating the levels of critical proteins , and their relevance in human disease and therapy is currently under investigation ( 12 ) .\nan increasing number of studies have demonstrated abnormal mirna expression levels in the central nervous system ( cns ) of cancer patients , suggesting that mirnas may serve as key regulatory components in cancer of the cns ( 5,10,13 ) .\nit was observed that 22 mirnas were upregulated and 26 mirnas were downregulated in the tumor tissue .\ningenuity pathway analysis ( ipa ) was used to analyze the regulatory network of the differentially expressed mirna in medulloblastoma .\nit was proposed that the pathways exhibited in the network may have an important role in the tumorigenesis of medulloblastoma .\nthe data were downloaded from the ncbi gene expression omnibus ( geo ) database ( gse42657 , www.ncbi.nlm.nih.gov/geo ) .\nthe data include 7 control samples ( consisting of 3 cerebellum and 4 frontal lobe controls ) and 9 medulloblastoma samples .\nthe data from all samples was normalized using the limma package in r software version 3.3.0 ( https://www.r-project.org/ ) .\nthe selected samples of this profile are exhibited in table i. the differentially expressed genes ( degs ) were obtained with the thresholds of |logfc|>1.0 and p<0.01 , using linear models and empirical bayes methods for assessing differential expression in microarray experiments in the limma package ( table ii ) .\na heat map of the different groups was produced to visualize the degs and cluster the corresponding groups with the differentially expressed mirnas from the tumor tissue , using the r package gplots ( fig .\nthe dataset ( 48 differentially expressed mirnas ) was uploaded to the ingenuity pathway analysis software version 2016 ( qiagen , inc . ,\nvalencia , ca , usa ) , using the microrna target filter to find the targeting information .\na total of 40 micrornas targeting 11,757 mrnas were identified by the filter . the core analysis function ( rapid assessment of the signaling and metabolic pathways , molecular networks , and biological processes that are most markedly perturbed in the dataset of interest ) to analyze the associated network functions of the mirnas .\nusing mirna microarray data from the geo database , 48 mirnas which are differentially expressed in medulloblastoma were identified , compared with the control group ( table ii ) .\nthe core analysis demonstrated the molecular network interactions and signaling pathways associated with 28 differentially expressed mirnas of medulloblastoma , and their predicted molecular targets were rebuilt using ipa . the network \norganismal injury and abnormalities , reproductive system disease , cancer had an ipa score of 41 , focusing on 17 mirna molecules , and the network cancer , organismal injury and abnormalities , cell death and survival had an ipa score of 23 , focusing on 11 mirna molecules ( fig .\nthe most impacted biological processes and diseases regulated by the analyzed mirnas included organismal injury and abnormalities , reproductive system disease and cancer .\nthe molecular network maps demonstrated that three primary components were identified to be at the central hub of the most significant network with a score of 41 ; these were tumor protein p53 ( tp53 ) , argonaute 2 ( ago2 ) and mitogen activated kinases 3 and 1 ( erk1/2 ) ( fig .\ntp53 , sirtuin 1 ( sirt1 ) and y box protein 1 ( ybx1 ) were located in the center of the second network with a core analysis score of 23 ( fig .\nthe first network included mir-17 - 5p , mir-130a-3p , mir-182 - 5p , mir-18a-5p , mir-19b-3p , mir-4288 , mir-96 - 5p , which were upregulated in the medulloblastoma samples , and mir-128 - 3p , mir-132 - 3p , mir-133a-3p , mir-299a-5p , mir-409 , mir-668 - 3p , which were downregulated . the second notable network ( fig .\n2b ) involved upregulated mir-217 - 5p and mir-216a-5p , and downregulated mir-329 , mir-330 and mir-584 , which are associated with the regulation of key regulatory genes in medulloblastoma development , including tp53 , sirt1 and ybx1 .\nhowever , when the cerebellum samples were used as the control , it was observed that 4 mirnas were overexpressed and 5 mirnas were underexpressed in the medulloblastoma ( table iii ) .\nthe network cell death and survival , gastrointestinal disease , hepatic system disease had an ipa score of 9 , focusing on 4 mirna molecules ( fig .\nmirnas function as master regulators and signal modulators by fine - tuning gene expression in multiple complex pathways .\na number of the mirnas which exhibit dysregulated expression in medulloepithelioma have been reported to serve various roles in carcinogenesis ( 6,7,9 ) . through analysis of a geo mirna expression profiling dataset , mirnas which are over- and underexpressed in medulloblastoma\nwere identified , including mir-217 , mir-216 , mir-183 , mir-182 and mir-96 , which are upregulated in tumor tissue .\nprevious research demonstrates that mir-183 - 96 - 182 regulates cell survival , proliferation and migration in medulloblastoma , and increased mir-183 - 96 - 182 expression is associated with aggressive clinical course , high rates of metastasis and poor overall survival ( 8,9,14 ) .\nmir-217 and mir-216 were overexpressed in medulloblastoma . however , the role of mir-217 was controversial .\nmir-217 is an oncogene that is overexpressed in aggressive human b cell lymphomas ( 15 ) .\nhowever , it may be a tumor suppressor in hepatocellular carcinoma ( 16 ) . in pancreatic intraepithelial neoplasm , pancreatic ductal adenocarcinomas and\nfurther studies are required to determine whether increased expression of mir-217 in medulloblastoma represents an oncogenic effect , or if the dysregulation functions as a potential tumor suppressor . while mir-216 was underexpressed in various types of cancer , including breast cancer , pancreatic cancer and nasopharyngeal carcinoma ( 1921 )\n, it may serve as a tumor suppressor to inhibit cell proliferation , invasion and tumor growth .\nfurther studies are required to determine whether increased expression of mir-216 in medulloblastoma represents an oncogenic effect or is a potential tumor suppressor . in the present study ,\nmarked downregulation of mir-383 , mir-206 , mir-138 , mir-128a / b and mir-133b was identified .\nmir-383 , repressing peroxiredoxin 3 at transcriptional and translational levels , suppressed the cell growth of medulloblastoma ( 6 ) .\nadditionally , mir-206 was downregulated in all the four molecular subgroups of medulloblastoma as well as in cell lines .\northodenticle homeobox 2 ( otx2 ) , a target gene of mir-206 which is overexpressed in all non - sonic - hedgehog - driven medulloblastomas , is an oncogene in medulloblastoma .\ntherefore , underexpression of mir-206 contributed to the upregulation of otx2 expression and enhanced growth of medulloblastoma cell lines ( 7 ) .\nstudies have demonstrated a reduction in the mirnas mir-383 , mir-138 , mir-128a / b , mir-133 , mir-124 and let-7 g in medulloblastoma .\nnevertheless , mir-328 , mir-133b , mir-149 , mir-181b and mir-154 were downregulated in the study of ferretti et al ( 5 ) and the present study .\nin addition , the present study revealed that mir-433 , mir-488 , mir-584 , mir-329 , mir-299 - 5p , mir-330 , mir-770 - 5p , mir-656 and mir-642 were underexpressed in medulloblastoma , and further research is required to identify whether these mirnas have a specific role in the tumorigenesis of medulloblastoma .\nbased on microarray analysis , mirnas that distinguish normal brain from medulloblastoma tissue were identified . as presented in the heat map ,\nthe dysregulated mirnas are more closely associated with the medulloblastoma samples compared with the normal control samples .\nadditionally , by uploading the mirnas from the first network to the ipa , it was identified that the dysregulated mirnas were associated with key regulatory genes in tumorigenesis , including tp53 , insulin - like growth factor 1 receptor , ago2 and erk1/2 .\nthe overexpressed mirnas mir-17 - 5p and mir-182 ( log fold change > 2 ) have interactions with tp53 ; studies have demonstrated an association between these mirnas and tp53 in tumorigenesis ( 22,23 ) .\nagos are associated with mirnas , due to their function in the rna induced silencing complex ( risc ) , wherein they use small rna guides to recognize targets .\nago2 had an interaction with mirnas that are dysregulated in medulloblastoma , including mir-17 - 5p , mir-128 , mir-96 , mir-433 , mir-383 and mir-138 .\nthe second network , including mir-217 and mir-216 , which are upregulated in medulloblastoma , exhibits associations with key regulatory genes in medulloblastoma development , including tp53 , sirt1 and ybx1 .\nsirt1 is a well understood member of the sirtuin protein class , preventing cell aging and apoptosis of normal cells ( 24,25 ) .\nthe effects of sirt1 are controversial ; the protein was considered to be a tumor promoter in neuroblastoma , prostate and skin cancer ( 2628 ) , whereas it was considered to be a tumor suppressor in breast and colon cancer ( 29,30 ) .\ntherefore , sirt1 may serve a role in medulloblastoma and correlate with the formation and prognosis of human medulloblastomas ( 31 ) .\nrecently , dey et al ( 32 ) proved that ybx1 ( yb1 ) is upregulated across human medulloblastoma subclasses and is required for medulloblastoma cell proliferation .\nfurthermore , the study identified that the shh : yap : yb1:igf2 axis may be a powerful target for therapeutic intervention in medulloblastoma . when the medulloblastoma samples were compared with the normal cerebellum , 9 dysregulated mirnas were identified .\nthe 9 mirnas were uploaded to the ipa in order to perform the core analysis .\nthe network involved 4 downregulated mirnas and was associated with important regulators of tumorigenesis , including met proto - oncogene ( met ) , akt serine - threonine kinase 1 and sterol regulatory element - binding factor 1 ( srebf1 ) .\nprevious evidence has demonstrated the association between aberrant met signaling and medulloblastoma development ( 33,34 ) .\nprevious studies have revealed that overexpressed mir-206 may inhibit met in lung cancer ( 35,36 ) , however the function of downregulated mir-206 in medulloblastoma is unknown .\nsrebf1 is a transcription factor , regulating lipogenesis , which is also involved in tumorigenesis ( 37 ) .\nthese network components alone are not sufficient to initiate medulloblastoma formation ; the interactions between these dysregulated factors and additional genetic insults promote tumorigenesis . in conclusion , based on the mirna array data in the geo database , mirnas which are differentially expressed in medulloblastoma samples were identified .\ncertain dysregulated mirnas have been confirmed ; however , further research is required to verify the mirnas which have not been previously identified .\nadditionally , the ipa core analysis , presenting the interaction of mirnas and counterpart targets , provides a method to understand the tumorigenesis of medulloblastoma .\nthe results of the present study may provide a potent target for therapeutic intervention or diagnosis in medulloblastomas .", "answer": "medulloblastoma is the most common malignant brain tumor of the central nervous system among children . \n medulloblastoma is an embryonal tumor , of which little is known about the pathogenesis . \n several efforts have been made to understand the molecular aspects of its tumorigenic pathways ; however , these are poorly understood . \n microrna ( mirna ) , a type of non - coding short rna , has been proven to be associated with a number of physiological processes and pathological processes of serious diseases , including brain tumors . \n differentially expressed mirnas serve an important role in numerous types of malignancy . \n the present study aims to define a differentially expressed set of mirnas in medulloblastoma tumor tissue , compared with normal samples , to improve the understanding of the tumorigenesis . \n it was identified that 22 mirnas were upregulated and 26 mirnas were downregulated in the tumor tissue compared with the normal group . however , when the medulloblastoma tissue was compared with normal cerebellum tissue , 9 mirnas were identified to be up or downregulated in the tumor samples . \n the differentially expressed mirnas in the tumor tissue were identified in order to clarify the networks and pathways of tumorigenesis using ingenuity pathway analysis . \n subsequently , key regulatory genes associated with the development of medulloblastoma were identified , including tumor protein p53 , insulin like growth factor 1 receptor , argonaute 2 , mitogen - activated protein kinases 1 and 3 , sirtuin 1 and y box binding protein 1 .", "id": 133} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA Synthesis of the Chlorosulfolipid Mytilipin A via a Longest Linear Sequence of Seven Steps\n\nPaper sections:\n\nThe chlorosulfolipids are a most unusual group of lipids known since the independent reports of chlorinated C22 lipids isolated from the alga Ochromonas danica by the Vagelos and Haines groups in 1969.[1,2] These first compounds were characterized as bis-sulfates of 1,14-docosanediol, with varying levels of chlorination up to the hexachloride, now known as danicalipin A (1, Figure 1). In the decades since, this family has grown to include ill-characterized C24 analogs (also from O. danica),[3] the unusual chlorovinyl sulfate-containing lipid malhamensilipin A (2) that was isolated from the related alga Poterioochromonas malhamensis by Slate and Gerwick,[4] and the mytilipins, a small group of lipids isolated in very small quantities from toxic Adriatic mussels and reported by Fattorusso and co-workers.[5,6] These last compounds include the C15 lipid mytilipin A (3), which has some structural resemblance to danicalipin A and malhamensilipin A, and mytilipins B and C (4 and 5), two C24 lipids with an astounding level of stereochemical complexity that includes 11 chlorine-bearing centers. More recently, Okino has uncovered more natural congeners in the danicalipin series in a careful study of O. danica,[7] and the Sheu group isolated analogs of mytilipin A from an octocoral from the Strait of Taiwan.[8] Given the diversity of sources and structures, it is reasonable to expect that more members will be added to the chlorosulfolipid family in the years to come.[9]
Over the past four years, several groups, including our own, have reported syntheses of members of the chlorosulfolipid family. The Carreira group registered the first synthesis when they disclosed an elegant route to racemic mytilipin A.[10] Shortly thereafter, our group reported the stereochemical elucidation of danicalipin A and its synthesis in racemic form,[11] followed by the structural revision and enantioselective synthesis of malhamensilipin A.[4b,12] These three syntheses featured similar overall strategies with introduction of the polar substituents via alkene oxidation reactions.[13] The Yoshimitsu group developed a substantially different approach, featuring their method for stereospecific deoxydichlorination of enantioenriched epoxides,[14] which culminated in clever asymmetric syntheses of both mytilipin A and danicalipin A,[15] the latter of which was contemporaneous with a third very different, creative approach from the Matsuda group.[16] Finally, the Carreira group recently reported the synthesis of the proposed structure of mytilipin B as shown in Figure 1, and came to the conclusion that this chlorosulfolipid requires stereochemical revision.[17]
We now report a new synthesis of mytilipin A via a longest linear sequence of only seven steps for racemic material, eight for enantioenriched chlorosulfolipid, with several key features: (1) a highly diastereoselective haloallylation of a sensitive \u03b1,\u03b2-dichloroaldehyde; (2) a kinetic resolution of a complex vinyl epoxide; (3) a convergent olefination via Z-selective alkene cross metathesis; and (4) excellent levels of stereocontrol throughout.
Crotyl alcohol was treated with molecular chlorine in the presence of Et4NCl to afford the anti-dichloride 7; presumably this procedure generates Mioskowski's reagent[18] (Et4NCl3) in situ. Oxidation with the Dess\u2013Martin periodinane followed by a careful workup afforded the sensitive and volatile aldehyde 8 in crude form, which was immediately converted to vinyl epoxide 9. The bromoallylaluminum reagent[19] shown added with high diastereocontrol consistent with both the Felkin\u2013Anh and Cornforth models,[20,21] and the resulting bromohydrin was converted to the epoxide upon treatment with aqueous base. The moderate yield in this case might be attributed to volatility of the intermediate aldehyde and the product vinyl epoxide; in related systems with longer alkyl chains, yields of about 75% have been obtained. Although strategically attractive in the context of the chlorosulfolipids, carbonyl addition reactions to \u03b1,\u03b2-dichloroaldehydes can be plagued by facile elimination reactions, and only Yoshimitsu has previously embraced this type of C\u2013C bond forming reaction en route to these targets.[15] In our studies, we have found that a variety of allylation reagents that presumably react via closed transition states provide products with high levels of diastereoselectivity and without destruction of the sensitive substrate.
The alkene partner 11 required for the convergent step was obtained in two steps from 8-bromo-1-octene. Formylation of the Grignard reagent derived from 10 followed by Takai chloroolefination[22] afforded 11 in multigram scale.
The key convergent bond-formation\u2014Z-selective alkene cross metathesis[23] using the Grubbs cycloadamantyl catalyst 12[24]\u2014generated Z-vinyl epoxide 13 with complete control of alkene geometry. We attribute the relatively low yield in this particular case to catalyst deactivation by the vinyl epoxide; however, this step compares favorably overall with previous syntheses of this type of epoxyalkene via poorly selective Wittig reactions that require several extra steps.[10\u201312] Unfortunately, we were unable to achieve effectively more than a single turnover with 12;[25] however, this reaction is notable for the ability to directly introduce the vinyl chloride, which eliminates at least three post-convergence steps.[10,15a] The success of the cross metathesis in the face of possible RCM pathways can be attributed to: 1. the intrinsically slow reactivity of vinyl chlorides; 2. the slow kinetics of cyclooctene formation; and 3. the high kinetic selectivity of catalyst 12 for Z-alkenes, which presumably prevents reaction with the E-vinyl chloride in either RCM or cross metathesis events. Vinyl epoxide chlorinolysis with inversion of configuration[11,12] proceeded smoothly under the conditions shown, providing diene 14. Uncertain about the reactivity of the isolated vinyl chloride relative to the particularly electron-deficient allylic chloride in 14, we were pleased to observe a completely chemoselective, highly diastereoselective (93:7 d.r. of crude product, purified to 97:3), and efficient chlorination using Mioskowski's reagent. The generation of hexachloride product 15 constitutes a formal synthesis of mytilipin A, and sulfation of the secondary alcohol according to Carreira's conditions[10] completes the seven step (longest linear sequence) synthesis of racemic chlorosulfolipid. This route has enabled the preparation of over 100 mg of the target molecule to date, with a nearly 9% yield over the entire sequence. Although the final steps of the synthesis are related to those previously reported by us and the Carreira group, our rapid access to 13 takes advantage of a completely new strategy designed for general access to several of the chlorosulfolipids.
The convergent Z-selective alkene cross metathesis to form 13 is noteworthy for its complete diastereoselectivity if not for its efficiency. To see if the extremely high selectivity we observed was general for vinyl epoxides, as well as to investigate the low catalytic activity of 12 with respect to the specific case in Scheme 1, we tested the reactivity of cis-3,4-epoxy-1-undecene (18) with 1-decene (eq 1). With 10 mol% catalyst 12, complete conversion to Z-vinyl epoxide 19 was observed (83% isolated yield, >20:1 Z:E). With 1 mol% catalyst, the product was isolated in 43% yield (incomplete conversion), with equal selectivity. Therefore, it appears that vinyl epoxides are subject to highly Z-selective cross metathesis with catalyst 12, and that the poor efficiency observed in the convergent step to form 13 is likely specific to chlorinated substrates of type 9.
In principle, adaptation of our route to the enantioselective preparation of mytilipin A simply requires access to enantioenriched dichloroalcohol 7. However, methods for the asymmetric dichlorination of alkenes, including the allylic alcohol substrates pertinent to our synthesis, are not yet at a level of sophistication appropriate for the first step in complex molecule synthesis.[26] We contemplated accessing enantioenriched dichloroalcohols using either the stereospecific deoxydichlorination of an optically active epoxyalcohol derivative according to the method of Yoshimitsu,[14] or by resolution. Because it would add only one step to the sequence, we opted to investigate resolution strategies. Unfortunately, attempts at kinetic resolution of dichloroalcohol 7 (and dichloroaldehyde 8) using a variety of approaches were unsuccessful; however racemic vinyl epoxide 9 could be resolved by adapting the meso-epoxide desymmetrizing chlorinolysis of Denmark and co-workers (Scheme 2).[27] The strong preference for ring-opening of the vinyl epoxide at the allylic position (as opposed to the position proximal to the electron-withdrawing chloride residues) is presumably key to success; a selectivity factor of 13 was realized, allowing for material of 93.5:6.5 e.r. to be obtained at 57% conversion (by NMR analysis) and in 43% isolated yield.[28] On the basis of this result, we have defined an eight-step enantioselective synthesis of mytilipin A.[29,30] More details about this interesting resolution will be forthcoming in a full account.
A few short years ago, the highly chlorinated lipids shown in Figure 1 might have appeared to be intractable problems for chemical synthesis, because of the dearth of previous work on stereochemically complex polychlorinated compounds. Now, with the recent advances made by several groups,[10\u201316] and with the design and execution of our new direct synthesis described here, it has become clear that the chlorosulfolipids can be assembled in a relatively straightforward fashion. The synthesis of racemic mytilipin A that we report requires only seven linear steps from commercially available starting materials and features only productive chemical transformations. Using kinetic resolution of a vinyl epoxide, enantioenriched chlorosulfolipid can be obtained with only one additional operation. Furthermore, our synthesis demonstrates that \u03b1,\u03b2-dichloroaldehydes can participate in efficient and highly stereoselective carbonyl addition reactions, and that Z-selective alkene cross metathesis is a powerful method for convergent olefination en route to the chlorosulfolipids. The successful application of these catalysts in this context further documents the ever-expanding reach of metathesis processes for stereocontrolled natural product synthesis.
", "answer": "The chlorosulfolipid mytilipin A has been synthesized in racemic form in only seven steps and in enantioenriched form in eight steps. Key transformations include a highly diastereoselective bromoallylation of a sensitive \\xce\\xb1,\\xce\\xb2-dichloroaldehyde, a kinetic resolution of a complex vinyl epoxide, a convergent and highly Z-selective alkene cross metathesis, and a chemoselective and diastereoselective dichlorination of a complex diene.", "id": 134} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nanterior cruciate ligament ( acl ) has a primary role in the limitation of anterior translation of the tibia as regards to the femur .\nthey are also important for the compensation of stability in the acl in the knee lesions and patients with acl .\nthe hamstring muscle weakness and hamstrings weak relationship with the quadriceps are risk factors for acl injuries .\none of the most commonly used treatments is the method in which knee flexor tendons are used as autograft . as shown in previous studies , after using this method reconstructed knee recovered up to the 90% of flexion muscle strength of counter knee ( harter et al .\n, 1990 ; lipscomb et al . , 1982 ; simonian et al . , 1997 ) .\nit is also shown in previous studies that semitendinosus which is also used as acl graft has regeneration potential from more proximal and with similar morphology ( eriksson et al . , 2001 ; ferretti et al .\nalthough there is a development of regeneration close to normal morphology ; knee flexors abnormalities in neurological function can be a barrier to motor units function by preventing their healing .\nhowever , morphological factors such as muscle atrophy in these patients is not the only factor that determines the maximum power ; in previous studies , it is shown that despite the absence of morphological abnormalities the afferent feedback deficiency from acl may interfere with the activation of gamma motor unit of the muscles around the knee ( konishi et al .\neven if the knee flexor tendon regeneration is morphologically normal and that motor unit complex may prevent the function of the knee flexors by causing neurologic abnormalities .\ntherefore , while comparing knee flexor muscle strength of patients who underwent acl reconstruction with normal uninjured knee , muscle weakness due to the possibility of neurologic abnormalities can not be ignored .\nafter acl reconstruction , which muscle groups are more affected from frequently developing thigh muscle atrophy is a matter of debate .\nmuscle strength tests are used to evaluate recovery of acl after treatment and the effectiveness of treatment .\naccording to the study carried out , after acl reconstruction using hamstring tendon grafts , weakness in the knee flexor muscle strength can be observed up to 24 months .\nin addition , previous studies showed that in patients who underwent acl reconstruction quadriceps muscle torque per unit volume is significantly lower compared the intact knee ( konishi et al . , 2007b ) .\nin our study , we aimed to evaluate the effect of thigh circumference difference between patients knees who were administered the acl reconstruction with hamstring tendon autograft and intact knees , on torque between the hamstring and quadriceps muscles .\nas is known , development of muscle weakness in quadriceps after acl lesions caused by neurological dysfunction was shown to be a natural consequence . in our study\n, we planned to evaluate the effect of thigh circumference difference between operated extremity and intact extremity on knee flexorsmuscle strength .\nfifty - five patients ( 54 males , 1 female , mean age 28.156.47 ) who underwent acl reconstruction in our clinic and with at least 6 months follow - up period available were included in our study . while choosing the patients , not having any disease nor interventions previously on intact knees has taken into account .\npatients who have symptoms and signs such as discharge , inflammation , instability , locking , limitation of motion , anxiety while exercising were removed from the study .\nall operations were applied in teaching and research hospital by the same surgeon . the condition that autogenous hamstring tendon graft usage in acl reconstruction was searched for the patients . in all patients , same postoperative rehabilitation program which is indicated below\nfor the first week walking with a full load , 090 of passive knee extension , bringing the active flexion , quadriceps and hamstring muscle training , heel shift , straight leg rise ; between 12 weeks , hamstring training in the prone position , asideleg lift , walkingin the water if a swimming pool exist ; between 23 weeks , terminal extension and hamstring stretch studies with weight ; 34 weeks , if knee flexion has reached to 90 the pedals ergonometric work , walking back in the pool ( if possible ) , doing full daily activities ; 612 weeks , rising at finger tips and starting to closed kinetic chain exercises , preparations for the transition to the sport aiming to increase strength , durability and propsiosepsiyo ; in the 3rd month , cycling , running and scissoring in water ; in the 4th month , in addition to weight training activities beginning to proprioceptive and on the stairs activities , doing straight running ; in 68 months beginning to sport - specific movements , ensuring to return to contact sports were taken into account . each patient was laid in the supine position , knees at full extension and relaxed position prior to measurement of the circumference of the thigh muscles .\nboth thigh circumference were measured and recorded from 15 cm proximal to the upper limit of the patella for measuring . the determined length difference between there constructed knee and the intact knee\npower measurements of quadriceps and hamstring muscle groups in patients extremities who underwent operation and who did not in were done by using cybex ii dynamometer ( humac ) . during the measurements the maximum torque ( peak torque ) values at 60/sec , 240/sec infrequency ,\nthe application of standard equipment , data collection and heating procedures were performed before the measurement .\npatients were told to continue their usual daily activities not to do tiring activities in the day before the test . on the test day before the beginning of measurements patients\npatients pelvis were stabilized with the help of a belt , thighs were supported with pillows , ankle cuff was placed directly on top of malleolar .\npatients forearms were positioned so that the rotational axis of the forearms were aligned with rotational axis of knees . during the test\nthe range of motion was adjusted to be 0 extension and 90 flexion . in order to get support patients\nwere allowed to hold seats on the sidebar during the test . before starting the recording of the data patients did three times sample repetition at both angle rates .\nconcentric exercise were carried out for 5 times in maximal flexion and extension to patients after one minute rest .\nfirst , 60/sec speed after a minute rest the test was continued with 240/sec speed .\nseveral patients developed thigh pain during measurements and measurements were repeated after the test was terminated .\nnumber cruncher statistical system ( ncss ) 2007 and power analysis and sample size ( pass ) 2008 statistical software ( utah , usa ) were used for statistical analysis . besides descriptive statistical methods ( mean , standard deviation , median , frequency , rate , minimum , maximum ) for qualitative comparison of data pearson s chi - square test , fisher - freeman - halton test , fisher s exact test , and yates continuity correction test ( yates adjusted chi - square ) were used for the evaluation of data .\nage identifier values and follow - up periods of patients are shown in table 1 .\nthigh circumference of intact extremity and operated extremity of patients are shown in table 2 .\npeak torque of the mean extensor and flexor muscle strength and percentage values relative to each other , are shown in tables 3 , 4 , and 5 .\nstatistically significant relationship was observed at the level of 66.0% percent between the thigh diameter difference and cybex extension 60 of patients in negative direction ( while the thigh diameter difference increasing the cybex extension 60 percent decreasing ) ( r : 0,660 ; p=0.001 ; p<0.01 ) .\nstatistically significant relationship was observed at the level of 55.0% percent between the thigh diameter difference and cybex extension 240 of patients in negative direction ( while the thigh diameter difference increasing the cybex extension 240 percent decreasing ) ( r : 0,550 ; p=0.005 ; p<0.01 ) ( fig .\nstatistically significant relationship was observed at the level of 55.0% percent between the thigh diameter difference and cybex flexion 60 of patients in negative direction ( while the thigh diameter difference increasing the cybex flexion 60 percent decreasing ) ( r : 0,555 ; p=0.002 ; p<0.01 ) .\nit was observed a relation between the thigh diameter difference and cybex flexion 240 of patients in negative direction ( while the thigh diameter difference increasing the cybex flexion 240 percent decreasing ) at the level of 28.1% percent and this situation was found to be statistically significant ( r : 0,281 ; p=0.079 ; p>0.05 ) ( fig .\nafter our study , in accordance with our findings it is still possible to encounter the thigh atrophy in average 28 months after acl reconstruction surgery even under physical rehabilitation programs and appropriate follow - up . in line with earlier studies , quadriceps muscle mass\nis often seen as responsible for the present thigh atrophy , however negative effects of the hamstring muscle group on muscle atrophy which is determined with manual thigh circumference measurements are undeniable .\nas shown in previous studies , in patients with acl lesions the development of neurological dysfunction is not available in the knee flexors comparing with quadriceps muscle group .\ncomparative studies which was done in patients with acl lesion and in patients without any knee problems showed that there was no significant difference between the speed of flexion and torque per unit volume of the knee flexor muscle . despite this ,\nin the same study it was found that isokinetic torque that occurred in the knee with acl lesions at 60/sec was less than robust knee ( konishi et al . , 2012 ) .\nin addition , it is shown that the acl reconstruction with hamstring tendon is not effective on muscle torque power of knee flexors and flexion speed of these muscles by showing that detection of changes in the robust knee is the same . in the light of these data\n, it might lead to think that acl lesions does not cause neurological dysfunction in the knee flexors . in another study\nthere was a comparison between patients who were administered to the acl reconstruction and patients who did not have any knee problem , it has been identified that muscle torque power on per unit volume of the quadriceps was significantly lower in the patients who were administered to reconstruction .\nin addition , quadriceps weakness is associated with the neurologic dysfunction that is developed after acl reconstruction has been shown by other researchers ( hart et al . , 2010 ; rice et al . , 2009 ; snyder - mackler et al .\nit has been shown that muscle weakness in the quadriceps that is induced by the acl lesions is a natural result linked to the development of neurological dysfunction . in our study\nwe have showed the loss of torque power of thigh atrophy on quadriceps at the 60/sec , 240/sec frequency even in the patients who have an appropriate rehabilitation program after acl reconstruction and under going follow - up process .\nalthough , it has been shown in previous studies that acl lesion development in the thigh did not lead to neurological dysfunction on hamstring ; in our measurements , it has been determined statistically that atrophy developed in the thigh is effective on the hamstrings muscle torque power at least as it is on quadriceps , especially 60/sec frequency .\nit could not be shown that this weakness is correlated to thigh atrophy as well as quadriceps at 240/sec flexion frequency .\nthese difficulties are likely to be related to neurological dysfunction occurred in the quadriceps muscles . due to different muscle weakness mechanisms which are developing according to the morphological structure and muscle properties , it is inevitable for the clinician to consider these changes in diagnosis and rehabilitation stages .\nthe point that we want to emphasize in our study is ; it ca nt be ignored that muscle weakness mechanisms developing in the thigh circumference vary according to the thigh muscle group and knee flexors play an important role in thigh atrophy when determining an appropriate rehabilitation program after anterior cruciate ligament reconstruction application .", "answer": "after anterior cruciate ligament ( acl ) reconstruction , which muscle groups are more affected from frequently developing thigh muscle atrophy is a matter of debate . \n we evaluate the effect of thigh circumference difference between patients knees who were administered the acl reconstruction with hamstring tendon autograft and intact knees , on torque between the hamstring and quadriceps muscles . \n fifty - five patients at least 6 months follow - up period available were included in our study . \n power measurements of quadriceps and hamstring muscle groups in patients extremities were done by using isokinetic dynamometer . \n the maximum torque values at 60/sec , 240/sec in frequency , positions of flexion and extension were determined . in accordance with our findings \n it is still possible to encounter the thigh atrophy in average 28 months after acl reconstruction surgery even under physical rehabilitation programs and appropriate follow - up . \n it is inevitable for the clinician to consider these changes in diagnosis and rehabilitation stages . \n it ca nt be ignored that muscle weakness mechanisms developing in the thigh circumference vary according to the thigh muscle group and knee flexors play an important role in thigh atrophy when determining an appropriate rehabilitation program after reconstruction application .", "id": 135} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngiant inflammatory ( filiform ) polyposis is an uncommon benign lesion and is usually associated with inflammatory bowel disease ( ibd ) .\nlong - term inflammation of the colonic mucosa during chronic ibd with alternating periods of ulceration and healing may lead to the formation of finger - like projections [ 1 , 2 ] . in rare cases , a giant inflammatory polyposis forms a large tumor mass [ 3 , 4 , 5 , 6 , 7 ] . on colonoscopy and radiologic studies ,\nnumerous filiform polyps appear as a mass of worms or as a fungating mass ; hence , this condition is easily confused with cancer .\ninflammatory polyps or pseudopolyps are the most common lesions observed both in ulcerative colitis ( uc ) and crohn 's disease ( cd ) [ 8 , 9 , 10 , 11 , 12 ] . moreover , in some cases , the polyps contain both mucosal and submucosal tissue , indicating initial inflammatory involvement of the deeper bowel layers .\nthey are composed of a central core of submucosal connective tissue coated by normal , non - inflamed mucosa . here ,\nwe report the case of a patient with uc with large tumors obstructing the transverse and descending colon , who presented with severe diarrhea and melena .\na 25-year - old japanese man with an uc history of 2 years and 6 months was successfully treated with prednisolone .\nthe disease was in remission and his symptoms had been relieved . however , the disease flared up and the patient was admitted to our hospital because of severe abdominal pain and bloody diarrhea .\nphysical examination revealed direct soreness and masses in the upper and left lower abdominal sites .\nblood examination revealed anemia ( hemoglobin level 5.5 g / dl [ normal 11.515.0 ] ) , hypoproteinemia ( protein level 4.6 g / dl [ normal 6.78.3 ] ) and hypoalbuminemia ( albumin level 1.9 g / dl [ normal 3.85.3 ] ) . computed tomography ( ct )\nimaging showed bowel wall thickening of the transverse and descending colon , which raised suspicion of wall thickening of several segments of the small bowel .\nthe ct scan also demonstrated localized high - density areas in the lumen of the transverse and descending colon ( fig .\na colonoscopy revealed a large mass with numerous white - pale reddish polyps of complex shape in the descending colon .\nbased on this examination , colon carcinoma was strongly suspected , and several biopsies were performed .\nhistology of the examined sections indicated uncharacteristic inflammatory changes in the mucosa , but no cellular dysplasia .\n, we observed one tumor measuring 23 18 cm in the transverse colon and another measuring 14 13 cm in the descending colon .\nthere were no obvious areas of ulceration , although each tumor had a coral - reef - like surface with numerous soft , finger - like polyps ( up to 5 cm in diameter ) projecting into the lumen .\nthe cross - section of the tumors showed that narrow strings of tissue were interconnected , forming multiple , variably sized spaces inside the tumors ( fig .\n2 ) . the surrounding fat tissue was unaffected , and no suspicious lymph nodes were detected .\nmicroscopic examination revealed that the tumors comprised strings of fibrotic connective tissue , lined by inflamed colonic mucosa , and the surrounding spaces were filled with fecal and mucoid materials .\na fibrovascular core and inflammatory polyposis were evident from the submucosa to the proper muscular layer and the submucosa had partially disappeared in both the elevated and the depressed lesions .\nthe polyps contained regenerative and hyperplastic muscularis mucosa with an arborized and thickened configuration ( fig .\nthe crypt architecture was normal , and no epithelial atypia of the polyps was noted . the mucosal inflammation consisted of lymphocytes , plasma cells , eosinophils and lymphoid follicles .\nneutrophil infiltration , cryptitis , crypt abscess , which is characteristic of active uc , and paneth cell metaplasia were found in the transverse colon ( fig .\nsections through the bowel wall near the mass showed colonic mucosa with regenerative features , including architecturally mildly distorted glands , but without active inflammatory changes ( fig .\nfinally , histopathological examination of the resected colon led to the diagnosis of giant inflammatory ( filiform ) polyposis associated with uc .\ninflammatory polyps are a common complication in patients with ibds such as uc and cd , accounting for approximately 1020% of all cases .\ninflammatory polyps may originate from the regenerative mucosa in the remission stage after an acute recurrence of uc or cd . in rare cases ,\nnumerous large - sized polyps are present , and this condition is known as giant inflammatory ( filiform ) polyposis [ 8 , 9 , 10 , 11 , 12 ] .\nthese polyps are associated with cd in approximately two - thirds of cases and with uc in one - third of cases .\ngiant inflammatory polyposis can be localized in one segment of the colon , or numerous polyps can be diffusely involved in the entire colon .\nthe transverse colon is the most common site , followed by the sigmoid and descending colon , the cecum and the splenic and hepatic flexures . in our case ,\nthe clinical features of the reported cases indicate that the time from the initial diagnosis of uc to confirmation of giant inflammatory polyposis ranged from 3 to 276 months . in our patient\npatients may present with various symptoms , including anemia , weight loss , cramping abdominal pain , diarrhea , passage of blood through the rectum and colonic obstruction .\nmost patients go undiagnosed until they develop signs and symptoms of obstruction , hemorrhage and anemia [ 1 , 2 , 14 ] .\nthe pathogenesis of giant inflammatory polyposis is considered to result from enlarged mucosal tags , caused by repeated peristalsis and fecal stream .\ngiant inflammatory polyposis may be related to postinflammatory regeneration or hyperplastic proliferation of the colonic mucosa between ulcerations .\nthe histopathological features include inflammatory infiltrates overlying the muscularis mucosae , deep fissure - like ulcers , chronic mucosal inflammation with lymphoid hyperplasia and nerve hyperplasia in the surrounding mucosa [ 1 , 2 , 4 , 5 , 6 , 15 ] .\ngiant inflammatory polyposis in uc may be a consequence of severe inflammation rather than of increased duration of the disease . in summary , we present the case of a japanese patient with uc who was diagnosed with giant inflammatory polyposis localized in the transverse and descending colon .\nsevere ulcerative inflammation and its repair process may have caused the development of the giant inflammatory polyps .", "answer": "we report a unique case of giant obstructing inflammatory polyposis associated with ulcerative colitis ( uc ) . \n a 25-year - old japanese man with an uc history of 2 years and 6 months was referred to our institution because of diarrhea and melena . \n his computed tomography scan showed marked dilation of the transverse and descending colon ; therefore , we performed total colectomy . \n macroscopic evaluation of the excised specimen indicated constricting lesions with giant polyposis in the transverse and descending colon . \n the polyposis consisted of narrow worm- or noodle - like polyps that bridged over the irregular ulcers . \n histologic evaluation of the excised specimen indicated transmural inflammation with a thickened proper muscular layer overlaid with inflammatory polyposis . based on these data , a diagnosis of giant inflammatory polyposis \n should be considered in patients who have had uc . \n although giant inflammatory polyposis is considered benign , surgical treatment may be indicated to avoid serious complications .", "id": 136} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmalignant glaucoma , or aqueous misdirection syndrome , is a condition characterized by sudden intraocular pressure ( iop ) elevation , and it is usually unilateral and induced by ocular surgical intervention or by medical therapy . here , we report a case of simultaneous bilateral malignant glaucoma in a young patient with no history of any ocular diseases .\na case of a 24-year - old female with no apparent previous history of ocular medical or surgical conditions was referred to our hospital because of recent bilateral iop elevation associated with a severe drop in vision and shallow anterior chamber with no posterior segment anomalies detected by ocular ultrasound in both eyes .\nyttrium aluminum garnet ( yag ) laser iridotomy dropped the iop only temporarily and the patient received topical atropine treatment with combined trabeculectomy and anterior vitrectomy .\nin this case , the patient had a typical presentation of bilateral malignant glaucoma and her iop dropped only temporarily following laser iridotomy to rise again shortly thereafter .\nalso , deepening of the anterior chamber and iop decrease after topical atropine was very supportive of the diagnosis of malignant glaucoma .\nthis is a very rare case of bilateral malignant glaucoma in a young adult without any prior eye conditions ; only one similar case has been reported in the literature .\nwe propose our own theory regarding this simultaneous occurrence of the pathology based on previously published studies about the presence of communication between the two eyes along the cerebrospinal fluid pathways .\nmalignant glaucoma , or aqueous misdirection syndrome , was first described by von graefe in 1869 as an aggressive form of postoperative glaucoma that is resistant to treatment and can result in blindness.1 this entity is characterized by intraocular pressure ( iop ) elevation , with shallowing to complete flattening of the anterior chamber ( ac ) in the presence of a patent peripheral iridectomy and in the absence of posterior segment anomalies , particularly suprachoroidal hemorrhage.2 malignant glaucoma is thought to occur in anatomically predisposed eyes,2 with one of the proposing mechanisms being posterior misdirection of the aqueous humor within or behind the vitreous substance .\nthis produces a continuous expansion of the vitreous cavity and increased posterior segment pressure , leading to anterior displacement of the lens iris diaphragm in phakic and pseudophakic eyes , or forward displacement of the anterior hyaloid face in aphakic eyes.3 this generates a vicious cycle , in that the higher the pressure in the posterior segment , the more firmly the lens is held forward .\nthe iop is classically markedly increased , but it may also be normal.4 malignant glaucoma has been reported in different situations , such as following cataract surgery , laser iridotomy , neodymium : yttrium aluminum garnet ( nd : yag ) cyclophotocoagulation or sclerotomy ; following glaucoma drainage device implantation , viscoelastic use , intravitreal injection of triamcinolone acetonide ; with aspergillus flavus intraocular infection ; and with the ingestion of topiramate or sulfa drugs.5,6 only a few cases of isolated malignant glaucoma have been reported in eyes without any antecedent eye diseases or surgery , and only one case of bilateral simultaneous idiopathic malignant glaucoma has already been reported in the literature.7 here , we report a case of spontaneous , simultaneous , bilateral malignant glaucoma in a young female with no systemic or eye diseases and no prior medical or surgical eye treatments .\nwe also propose a postulated mechanism that might explain the simultaneous bilaterality of this case .\nthe patient is a 24-year - old female who was referred to our eye center in mediclinic dubai mall , dubai , united arab emirates , because of recent bilateral iop elevation with a severe drop in vision .\nshe had been hospitalized elsewhere 1 week earlier because of severe bilateral frontal headache , nausea , and vomiting .\nblood tests and brain magnetic resonance imaging ( mri ) were performed and revealed no abnormalities . during her stay\nafter 5 days in hospital , the patient complained of loss of vision in the right eye , and after approximately 6 hours , also in the left .\nthe ophthalmology consultant suspected bilateral acute angle - closure glaucoma as a possible cause for the severe bilateral loss of vision .\ngoldmann applanation pressure was > 60 mmhg in both eyes ; the patient presented with severely miotic pupils and flat chambers , with almost iridocorneal touch centrally , cloudy corneas , and severe bulbar conjunctival injection .\nthe patient s past history was negative for any medical or surgical diseases and her eye history was also negative .\nof note , a routine eye examination had been performed a few months earlier and was reported to be normal .\ninitial management at our center consisted of multiple topical antiglaucoma medications and intravenous acetazolamide ( 500 mg ) .\nultimately , we managed to perform bilateral nd : yag laser peripheral iridotomy despite the corneal clouding .\nafter the peripheral iridotomy , the iop dropped in both eyes to around 45 mmhg , but it rose back to its original level after less than half an hour .\nthe diagnosis of bilateral malignant glaucoma was raised and the patient was admitted to hospital for surgical management .\ntopical atropine 1% drops and intravenous mannitol ( 1 g / kg of body weight ) were started , and the patient was put under continuous monitoring . in less than 2 hours ,\nthe acs started to deepen in both eyes , with partial clearing of the corneas .\nthe iop dropped again to 45 mmhg in both eyes . at that stage , the possibility of bilateral malignant glaucoma as a diagnosis was more likely .\nthe next day , the patient was scheduled for trabeculectomy with mitomycin - c ( 0.02% for 2 minutes ) combined with pars plana vitrectomy .\ninformed consent was obtained from the patient prior to surgery . in the meantime , overnight treatment with topical atropine and antiglaucoma medications was continued , along with intravenous acetazolamide .\na second dose of intravenous mannitol was repeated 1 hour before the planned surgery . at the time of surgery ,\nsurgery was performed in the right eye as planned , and the same procedure was carried out in the left eye 1 day later . in brief , the surgical procedure was performed in both eyes as follows : a limbus - based conjunctival flap was performed , followed by topical 0.2% mitomycin - c application for 2 minutes ; prior to the dissection of a 33 mm half - thickness trabeculectomy flap , one - port limited core vitrectomy was performed through a pars plana approach 4 mm from the limbus .\nafter completion of the vitrectomy , the trabeculectomy was completed by entering the ac through a small sclerotomy opening using a super blade .\nthe trabeculectomy flap was sutured back using two 10 - 0 nylon titrated sutures , and the conjunctiva was closed using running 8 - 0 vicryl ( johnson & johnson , new brunswick , nj , usa ) .\npostoperatively , the patient was put on a topical combination of tobramycin ( 3 mg / ml ) and dexamethasone ( 1 mg / ml ) , and atropine was continued once a day for 2 weeks .\nboth eyes had well - formed superior blebs and , surprisingly , visual acuity returned to 20/20 without correction , and there was no optic nerve ( on ) damage in either eye .\nthe iop remained < 18 mmhg all throughout the postoperative follow - up period , which extended for more than 1 year , with both eyes maintaining deep chambers and reactive pupils .\nthe study was approved by the review board / ethics committee of the beirut eye specialist hospital , beirut , lebanon .\nthe main features of malignant glaucoma ( or aqueous misdirection syndrome ) include : increased iop ; the presence of shallowing to complete flattening of the ac ; the absence of posterior segment anomalies particularly suprachoroidal hemorrhage ; no response to peripheral iridectomy ; and adequate response to topical atropine.2,7 malignant glaucoma is difficult to treat and characteristically progresses to blindness.2 in our case , the patient had a typical presentation of malignant glaucoma and the iop dropped only temporarily after laser iridotomy , to rise again shortly thereafter . also , deepening of the ac and iop decrease after topical atropine was very supportive of the diagnosis of malignant glaucoma .\nalthough malignant glaucoma typically occurs in predisposed eyes , especially among those subjected to surgical or medical therapy , only a few cases have been reported where isolated malignant glaucoma occurs without a previous history of any kind of treatment and , to the best of our knowledge , only one case of bilateral simultaneous idiopathic malignant glaucoma has been reported in the absence of any history of previous systemic or eye diseases.7 as such , our case is considered as the second report of bilateral idiopathic malignant glaucoma .\nthe rare phenomenon of malignant glaucoma occurring simultaneously in both eyes of young patients who do not have any predisposing factors is highly unusual and warrants exploration .\nmalignant glaucoma is thought to occur in anatomically predisposed eyes,2 with one of the proposed mechanisms being posterior misdirection of the aqueous humor within or behind the vitreous body , which leads to anterior displacement of the iris lens diaphragm and anterior hyaloid face.3 in our case , the occurrence of malignant glaucoma in one eye ( most probably the right eye first , as deduced from the patient s own story ) was in an anatomically predisposed eye , and the aqueous entrapped behind the vitreous established a pressure gradient between the on head and the cerebrospinal fluid ( csf ) in the subarachnoid space ( sas ) of the on .\nthis pressure gradient encouraged fluid movement toward the sas of the on and subsequently to the sas of the brain .\nmigration of fluid to the sas of the controlateral on could occur directly through the optic chiasm , or it could be mediated by the elevated csf pressure within the sas of the central nervous system through the phenomenon of bidirectionality of csf flow.8 this proposed mechanism of aqueous humor migration from the vitreous cavity to the on and csf of the brain is also supported by the observation of silicone oil ( so ) migration from the vitreous cavity to the on and to the brain in vitrectomized eyes.9,10 also , espinosa et al11 reported the migration of so into the on of the contralateral eye causing optic neuritis .\nthis migration is facilitated if there is a gradient of pressure between the vitreous cavity and the csf , or in a predisposed on head , such as in the presence of an on pit.12\nin conclusion , one possible explanation for the occurrence of simultaneous bilateral malignant glaucoma is that the entrapment of aqueous humor behind the posterior vitreous face can establish a pressure gradient between the vitreous cavity and the fluid around the orbital on .\nthis facilitates the migration of fluid to the sas of the on , and then to the sas of the contralateral orbital on , either directly through the optic chiasm or due to increased intracranial csf pressure .\nthe fluid subsequently migrates to the vitreous cavity of the contralateral eye and pushes the total vitreous core anteriorly ; this precipitates forward movement of the anterior hyaloid face and lens iris diaphragm , resulting in malignant glaucoma in the contralateral eye .\nthis postulated mechanism could also explain the observed phenomenon of immediate constriction of the contralateral pupil when a strong miotic agent is injected into the ac of the first eye upon completion of the phakic posterior chamber intraocular lens ( piol ) implantation in a planned bilateral piol surgery .\ngiven this observed phenomenon , we avoid the injection of miotic agents into the ac upon completion of surgery on the first eye in the setting of bilateral implantation of phakic piol .\nalthough it is very rarely indicated in our surgical practice of cataract surgery , the same phenomenon is observed during bilateral cataract surgery .\none more lesson to learn from this case is that severe iop elevation causes symptoms that can mimic those of certain central nervous system disorders .\nfinally , the diagnosis of idiopathic malignant glaucoma is challenging because , on the one hand , it is an uncommon entity , and on the other hand , early intervention with vitrectomy could possibly maintain good visual acuity and prevent blindness .", "answer": "purposemalignant glaucoma , or aqueous misdirection syndrome , is a condition characterized by sudden intraocular pressure ( iop ) elevation , and it is usually unilateral and induced by ocular surgical intervention or by medical therapy . here , we report a case of simultaneous bilateral malignant glaucoma in a young patient with no history of any ocular diseases.case reporta case of a 24-year - old female with no apparent previous history of ocular medical or surgical conditions was referred to our hospital because of recent bilateral iop elevation associated with a severe drop in vision and shallow anterior chamber with no posterior segment anomalies detected by ocular ultrasound in both eyes . \n yttrium aluminum garnet ( yag ) laser iridotomy dropped the iop only temporarily and the patient received topical atropine treatment with combined trabeculectomy and anterior vitrectomy.resultsin this case , the patient had a typical presentation of bilateral malignant glaucoma and her iop dropped only temporarily following laser iridotomy to rise again shortly thereafter . \n also , deepening of the anterior chamber and iop decrease after topical atropine was very supportive of the diagnosis of malignant glaucoma . \n successful management with trabeculectomy and limited vitrectomy also affirmed the diagnosis of malignant glaucoma.conclusionthis is a very rare case of bilateral malignant glaucoma in a young adult without any prior eye conditions ; only one similar case has been reported in the literature . \n we propose our own theory regarding this simultaneous occurrence of the pathology based on previously published studies about the presence of communication between the two eyes along the cerebrospinal fluid pathways .", "id": 137} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nperiodontal health can be described as a dynamic state where the activity of proinflammatory / antimicrobial cytokines to control infection is optimally balanced by anti - inflammatory mechanisms to prevent unwarranted inflammation . in subjects susceptible to periodontal disease ( pd ) , an imbalance of the inflammatory response results in excessive production of proinflammatory cytokines and the subsequent loss of periodontal attachment . on the other hand ,\nfurthermore , the release of tissue regenerating factors may contribute to periodontal regeneration by regulating the function of periodontal ligament cells , endothelial cells , and cementoblasts . in this\nsetting , neurotrophin brain - derived neurotrophic factor ( bdnf ) has been reported to enhance periodontal tissue regeneration [ 4 , 5 ] .\nbdnf is a member of the neurotrophin family which is expressed by vascular endothelium and osteoblastic , immune , and neuronal cells .\nbdnf is reported to be involved in the joint inflammatory process and its production is increased in response to proinflammatory cytokines . although a role for bdnf in periodontal regeneration has been proposed , no information is available concerning bdnf and periodontal disease .\nthe aim of this study was to measure the levels of bdnf in periodontal tissues from patients with chronic periodontitis .\nthe presence of polymorphisms rs6265 and rs4923463 of the bdnf gene and its correlation with inflammatory and clinical parameters were also assessed .\ntwenty - eight patients with cp , treated at the periodontal clinic , school of dentistry , at universidade federal de minas gerais ( ufmg , brazil ) , were enrolled in this study .\npatients in this study met the following inclusion criteria : previous history of cp , diagnosed according to previously described criteria : ( 1 ) exhibiting more than one tooth with probing depth higher than 5 mm , ( 2 ) exhibiting more than two sites with clinical attachment loss deeper than 6 mm , and ( 3 ) exhibiting lesions distributed in more than two teeth in each quadrant .\npatients who met the following criteria were excluded : ( 1 ) having a history of smoking , ( 2 ) use of antibiotic , ( 3 ) usage of anti - inflammatory and/or immunosuppressive medications during the 6 preceding months , and ( 4 ) a history of any systemic diseases ( i.e. , immunologic and autoimmune disorders , diabetes mellitus ) .\nthe control group ( hc ) comprised 29 age and gender matched periodontally healthy patients enrolled for third molar removal surgery .\nperiodontal examination was performed in both groups of patients , cp and hc , at the initial visit to determine probing depth ( pd ) , clinical attachment loss ( cal ) , and bleeding on probing ( bop ) .\nmeasurements were performed full - mouth at 6 sites per tooth ( mesiobuccal , midbuccal , distobuccal , mesiolingual , midlingual , and distolingual ) .\nall the measurements were performed by the same examiner . at the time of the examination a peripheral blood sample\nperiodontal tissue samples from periodontal pockets or healthy oral mucosa extracted during surgery of impacted third molars were fixed in 10% buffered formalin , embedded in paraffin wax , and cut longitudinally ( 3 m ) .\nthe sections were deparaffinized , rehydrated , and stained with h&e for evaluation of the inflammatory infiltrate .\ninflammatory cells were counted in four fields in two independent sections , using a light microscope ( axioskop 40 zeiss ; carl zeiss , gottingen , germany ) at 400x magnification .\nthe concentrations of the il-17a , bdnf , il-10 , and tnf- and the chemokine cxcl10 were measured in periodontal tissues by enzyme - linked immunosorbent assay ( elisa ) using commercially available kits ( r&d systems , minneapolis , mn , usa ) .\nthe lower limit of detection for each cytokine was 15 pg / ml , 3.9 pg / ml , 5.5 pg / ml , 20 pg / ml , and 4.5 pg / ml , respectively , for il-17a , il-10 , tnf- , bdnf , and cxcl10 . the data were determined using a standard curve prepared for each assay and expressed as picograms of cytokine / chemokine per 100 mg of tissue .\nperiodontal tissue samples were also used for determination of myeloperoxidase ( mpo ) activity , a neutrophil enzyme marker , as described earlier .\nthe mpo activity in homogenized periodontal tissues was evaluated by enzymatic reaction and absorbance was measured at 450 nm .\nthe mpo content was expressed as relative units calculated from standard curves based on mpo activities from 5% casein peritoneal - induced neutrophils assayed in parallel .\ntotal genomic dna was extracted from blood samples using qiaamp dna blood mini kit ( qiagen , valencia , ca , usa ) according to manufacturer 's instructions .\nquality , integrity , and quantity of dna were analyzed by nanodrop spectrophotometer ( thermo scientific , wilmington , de , usa ) .\nall amplifications were carried out in an abi 7900h thermal cycler ( applied biosystems , foster city , ca , usa ) using taqman genotyping master mix and following manufacturer 's recommended amplification conditions .\nchi - square test analysis was used to test for deviation of genotype frequencies from hardy - weinberg equilibrium .\nthe levels of cytokines in periodontal tissues and the frequency of gene polymorphisms were compared by the student 's t - test and chi - square tests .\nthe sample included in the current study was composed by age and gender matched groups .\nthe clinical features pd , cal , and bop were significantly higher in the cp than in the hc group ( p < 0.0001 ) ( table 1 ) .\nthe levels of il-17a , cxcl10 , il-10 , tnf- , and bdnf in periodontal tissues were greater in cp patients than in controls ( figure 1 ) .\nmoreover , the mpo activity and the inflammatory infiltrate in the periodontal tissues , characterized by polymorphonuclear and mononuclear leukocytes , were significantly higher in the cp than in the hc group ( figure 2 ) .\nthe bdnf and il-10 levels in periodontal tissues were negatively correlated ( r = 0.691 , p = 0.002 ) , whereas no correlation between bdnf and il-17a , tnf- , cxcl10 , or clinical parameters was observed ( pd , cal , and bop ) . following the clinical investigation , the frequencies of polymorphisms ( bdnf ) were assessed in blood samples of hc and cp subjects ( table 2 ) . the frequency of these genotypes agreed with the hardy - weinberg equilibrium ( p > 0.05 ) .\nthe distribution of the bdnf polymorphisms was similar between the groups ( table 2 ) .\nwe also investigated whether some of these polymorphisms were associated with worse clinical periodontal parameters .\nas shown in table 3 , no differences in clinical parameters were found when comparing the genotypes .\nthe levels of bdnf and the inflammatory mediators cxcl10 and tnf- were increased in gg genotype of bdnf rs6265 polymorphism ( figures 3(a ) , 3(b ) , and 3(c ) ) , but mpo levels did not alter significantly ( figure 3(d ) ) . in bdnf\nrs4923463 polymorphism the levels of bdnf and mpo did not differ , but the levels of cxcl10 and tnf- were higher in patients with aa genotype ( figures 3(e)3(h ) ) .\na wide range of nonneural cells in peripheral tissues or in the immune system expresses neurotrophins and their receptors .\nthus , the mitogenic and immune regulatory functions of neurotrophins have been discussed [ 6 , 1012 ] .\nthe neurotrophin bdnf is reported to be involved in inflammatory reactions , and its production is increased in response to proinflammatory cytokines .\nthe present study is the first to demonstrate that bdnf levels were increased in periodontal tissues from chronic periodontitis compared to healthy subjects . in agreement with our findings\n, bdnf was found in high levels in the plasma of patients with osteoarthritis and in patients with rheumatoid arthritis .\nwhile some authors reported that bdnf levels were significantly correlated with self - reported pain , others did not find association between bdnf and clinical parameters of arthritis .\nseveral studies analyzed bdnf rs6265 polymorphisms in psychiatric disorders [ 1618 ] . to date , few studies examined the rs4923463 polymorphism [ 16 , 1820 ] .\nwhile one study found correlation between snp rs4923463 and attention - deficit / hyperactivity disorder , schizophrenia , and risk of suicide in bipolar disorder , another study did not find any correlation between schizophrenia and rs4923463 polymorphism .\npreviously , two studies have evaluated the effects of bdnf polymorphisms in bone [ 21 , 22 ] , but there are no available studies in periodontal disease . in the present study we did not find differences in bdnf genotype distribution between patients with cp and controls .\nnevertheless , we found that subjects with gg ( rs6265 ) genotype expressed higher levels of bdnf in periodontal tissues , in agreement with a previous report showing that bdnf - m66 variant alters intracellular trafficking and impairs bdnf secretion . on the other hand , rs6265 polymorphism\ninterestingly , the snp rs6265 was reported as a phossnp , which means this snp regulates protein phosphorylation .\nthe snp rs6265 affects substrate - kinase interaction between bdnf protein and chek2 kinase and regulates bdnf phosphorylation at site t62 .\nsubjects aa genotype carriers exhibited lower bone mineral density compared to g carriers . specifically , bdnf - v66 ( major allele g at rs6265 ) transfection significantly increases expression of osteoblast specific markers ( opn , bmp2 , and alp ) and promotes osteoblast differentiation and maturation in cell culture .\nan association of rs6265 with bone metabolism was also suggested in the largest meta - analysis involving 32,961 individuals of european and east asian ancestry .\nthey found that homozygous minor allele a carriers ( aa ) have significantly decreased bmd compared to major allele g carriers ( ga and gg ) .\nit has been reported that bdnf is able to induce an increase in il-10 expression . however , a negative correlation between the production of bdnf and il-10 was observed in samples from patients with periodontitis .\nil-10 can inhibit the release of proinflammatory cytokines from monocytes / macrophages and can therefore inhibit the lipopolysaccharide- and ifn--induced secretion of inflammatory cytokines ( e.g. , tnf- , il-1 , il-6 , cxcl8 , and others ) . in periodontal disease , il-10 is thought to be associated with lower disease severity .\nprevious studies demonstrated that bdnf induces periodontal tissue regeneration by activation of cementoblasts differentiation , vascular endothelial cell migration , and also has a positive effect on bone remodeling [ 5 , 28 ] .\nthis data together suggested that bdnf has a role in bone remodeling and any change in this neurotrophin levels could have an impact in bone repair .\nfinally , we observe that cp subjects with gg ( rs6265 ) and aa ( rs4923463 ) genotypes demonstrated increased levels of tnf- and cxcl10 .\ncxcl10 has several roles , such as chemoattraction of macrophages , t cells , nk cells , and dendritic cells .\nin addition , previous studies showed that exposure to bdnf substantially and synergistically enhanced tnf- levels in vitro , and tnf- preconditioning increased proliferation , mobilization , and osteogenic differentiation in vitro .\nwe can hypothesize that the concomitant increase of bdnf , tnf- , and cxcl10 in patients with the gg genotype may be an attempt of the host to induce periodontal healing .\nso , maybe if these patients were examined after periodontal treatment , they could display higher and better levels of tissue regeneration compared to patient who do not exhibit the gg genotype .\nin conclusion , bdnf seems to be related to periodontal pathogenesis and also involved in tissue repair .\nthe results obtained here provide a benchmark for future studies with a large cohort of patients to help strengthen and understand the influence of neurotrophins in periodontal disease .", "answer": "brain - derived neurotrophic factor ( bdnf ) is a member of the neurotrophic factor family . outside the nervous system \n , bdnf has been shown to be expressed in various nonneural tissues , such as periodontal ligament , dental pulp , and odontoblasts . \n although a role for bdnf in periodontal regeneration has been suggested , a function for bdnf in periodontal disease has not yet been studied . \n the aim of this study was to analyze the bdnf levels in periodontal tissues of patients with chronic periodontitis ( cp ) and periodontally healthy controls ( hc ) . \n all subjects were genotyped for the rs4923463 and rs6265 bdnf polymorphisms . \n periodontal tissues were collected for elisa , myeloperoxidase ( mpo ) , and microscopic analysis from 28 cp patients and 29 hc subjects . \n bdnf levels were increased in cp patients compared to hc subjects . \n a negative correlation was observed when analyzing concentration of bdnf and il-10 in inflamed periodontium . \n no differences in frequencies of bdnf genotypes between cp and hc subjects were observed . \n however , bdnf genotype gg was associated with increased levels of bdnf , tnf- , and cxcl10 in cp patients . in conclusion \n , bdnf seems to be associated with periodontal disease process , but the specific role of bdnf still needs to be clarified .", "id": 138} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n hepatitis b virus ( hbv ) is a major health problem , with approximately 400 million chronically infected people worldwide , and 1560% of the normal population in many african countries may be positive for one or more of the serological markers of hepatitis b virus infection .\nthese chronically infected patients not only are at an increased stage of developing liver cirrhosis and hepatocellular carcinoma , but also serve as a potential reservoir of infection . the major structural protein of virus envelope , hepatitis b surface antigen ( hbsag ) , is universally considered as a diagnostic marker of hbv infection .\nthe absence of hbsag in the serum and the presence of antibodies to core antigen ( anti - hbc ) usually indicate resolved infection .\noccult hbv infection ( obi ) usually has a serological evidence of previous hbv infection that has been described in a few cases .\nhiv coinfection has been reported to modify the natural history of hbv with potential consequences on morbidity and mortality .\ndata on obi in art untreated hiv patients is limited from a vast number of african countries like nigeria , where prevalence of hbv monoinfection , mode of transmission , viral genotype , and mutational pattern varies considerably in different parts of the country .\nno previous study from nigeria on prevalence on obi among any groups has been carried out .\nthis is particularly important as exposure to hbv is common among hiv - infected cases because of shared routes of transmission .\nnotably , there is considerable variation in prevalence of hiv / hbv coinfection according to geographic regions and exposure risk .\nsuccessful implementation of art leads to immune reconstitution that can potentially result in immune mediated liver injury in the setting of hbv coinfection .\nsome studies have reported an association between obi and elevated transaminase ; therefore identification of obi is of importance .\nof the 1,200 hiv - infected patients enrolled in the haart clinic of the specialist hospital , ikole , ekiti state , nigeria , from october , 2012 , to april , 2013 , we identified 980 hbsag negative patients ( art - nave subjects ) . among them , 188 were selected for the study by a simple random method .\ninformed consent was obtained from the patients , and the institutional committee approved the study protocol .\nall samples were tested for hbsag , anti - hbs , anti - hbc , anti - hcv , and anti - hiv using elisa ( drg diagnostics , marburg , germany ) .\nall anti - hbc positive samples were retested for hbsag as well as for anti - hbc , and only repeat positive samples were included in the study .\ndna was extracted from all the serum samples using qiaamp dna blood mini kit ( qiagen gmbh , hilden , germany ) following the manufacturers ' instructions .\nbriefly , samples ( 200 l ) were incubated with protease and lysis buffer .\nafter incubation , there were two washing steps , and the nucleic acids were eluted in a volume of 50 l of elution buffer .\nthe presence of hbv dna was examined in all samples using a routine diagnostic pcr .\nprimer pairs were designed from the highly conserved overlapping regions of the s and p genes of the hbv genome .\na nested pcr was performed : outer primer pairs were hbpr134 ( sense ) 5-tgctgctatgcctcatcttc-3 and hbpr135 ( antisense ) 5-cagagacaaaagaaaattgg-3 and the inner primer pairs were hbpr75 ( sense ) 5-caaggttatgttgcccgtttgtcc-3 and hbpr94 ( antisense ) 5-ggtataaagggactcacgatg-3. pcr amplifications were carried out in 25 l reaction volumes with 5 ng of genomic dna , 10x pcr buffer ( 20 mm tris - hcl ph 8.4 , 50 mm kcl ; qiagen ) , 2 mm of dntps , 50 ng of each primer , and 1 u ampli taq gold dna polymerase ( applied biosystems ) on a ptc 200 cycler ( peltier thermal cycler watertown , massachusetts , usa ) .\nthermal cycling parameters were initial denaturation at 94c for 2 min , followed by 35 cycles of 30 sec at 94c denaturation , 30 sec at 52c annealing temperature , and 45 sec at 72c extension , followed by a final extension of 5 min at 72c .\nthermal cycling parameters remained the same as in the first pcr round except for the number of cycles that is increased to 40 cycles of amplification .\neach pcr product ( 5 l ) was analysed by electrophoresis in 2% agarose gels . a positive control ( hbv plasmid dna ) and a negative control of the master mix only were integrated to each run to validate the pcr products that yielded a 340 bp fragment .\nquantification of hbv dna was performed with quantitative real - time pcr using a previously described procedure in a geneamp 7300 sequence analyzer ( applied biosystems , perkin - elmer , foster city , ca ) .\nhbv - plasmid dna was used to generate a standard curve following a serial 10-fold dilution .\nmean age and all the numerical data were analysed using student 's t - test .\nthe chi - square test and fisher 's exact test were used to compare categorical data . for the purpose of our study ,\nthe demographic , biochemical , and virological parameters of the study group are summarized in table 1 .\nthe mean age was 35 ( range : 367 ) years . the majority ( 45% ) had multiple sexual partners and 25% of the subjects had a history of concomitant alcohol use .\noverall , 29/96 ( 29.2% ) of patients were reactive for anti - hbc , an indication of prior exposure to hbv dna , and majority 6/8 ( 75% ) of the patients were female ( table 2 ) .\nthus , in the total study population , 21/188 ( 11.2% ) of patients were identified as obi and 62.5% of the obi patients had cd4 count less than 200 cells / mm .\naveragely the hbv viral load was < 50 copies / ml in the obi samples examined by quantitative pcr .\nserum levels of ast and alt were higher among patients with obi in comparison to anti - hbc positive hbv dna negative individuals , but the difference failed to reach standard significance ( p = 0.13 and p = 0.07 ) , respectively .\nthe comparison of different demographic , biochemical , and virological factors between hbv dna positive and negative cases was illustrated in table 3 .\nthe distribution of the study participants as per the 1993 revised classification system for hiv infection and expanded surveillance case definition for aids among adolescents and adults was as shown in table 4 . \nthe present study represents a comprehensive cross - sectional analysis of prevalence of obi in an art nave hiv positive cohort comprising various risk groups .\nmost previous studies looking at the clinical effects of obi in hiv include a large number of patients on anti - hbv drugs as a component of art .\nthis study describes the risk factors associated with obi , frequently of anti - hbc positivity and its possible values as a serological marker for identifying hiv - infected patients who benefit from hbv dna assay .\nwe found the prevalence of occult hbv to be 11.2% among a random selected group of hiv - infected patients .\nthe prevalence of obi in hiv positive individuals varies worldwide between 0 and 90% , depending on the geographic regions , risk factors , and the exposure involved . in the present study ,\nthe prevalence of anti - hbc ( 29.2% ; 28 of 96 ) and obi ( 28.6% ; 8 of 28 ) among the art nave hiv positive cohort was higher compared to previous report on blood donors from studies done in areas of india , areas which reported 21.3% obi among the hbsag negative anti - hbe positive donors . within nigeria , hbv and hcv coinfection among hcv - infected patients\nmost of the previous studies on hbv / hiv co - infection are aimed at detecting hbv prevalence in the hiv population are based on hbsag positivity ( prevalence 9.9 to 11% ) , but reports on obi are scarce .\na previous study on intravenous drug users in northeastern india detected a prevalence of 15.9% . among the obi cases , the rate of anti - hbs was lower ( 2/8 ; 25% ) , which may be due to the fact that hiv - infected patients are prone to lose anti - hbs immunity at a higher frequency than the general population .\nprevious reports suggested that the lower hbv replication was associated with milder hepatic damage . among the subjects with obi , elevated alt or ast\nhowever , our study is cross - sectional ; therefore evaluation of long term clinical significance of obi should be better addressed by follow - up studies .\nthe low level of viral load obtained in this study buttress the findings in another study that showed that showed that almost all obi cases are infected with replication incompetent hbv , revealing a strong suppression of overall replication activity and gene expression , thereby resulting in a significant reduced viral load .\nhiv patients are screened for concomitant chronic hepatitis b using hbsag elisa , and it is not considered cost - effective to perform hbv dna testing for all hiv patients in our resource - poor setting . our study tried to identify possible clinical and serological markers which could guide dna testing in these patients .\nobi is reported to be common among hcv infection , but we found its prevalence to be low among our study group\n. however , anti - hcv was not tested among the other hiv positive samples attending the specialist hospital , ikole , ekiti state , nigeria .\nfurthermore , none of the risk factors were found to be statistically significant markers of obi and can not be used as an independent marker for identifying patients who should benefit from hbv dna estimation .\nhowever , as one third of the anti - hbc positive negative patients were positive for hbv dna ( 8 of 28 ) , it is recommended that hiv positive patients with hbsag negative / anti - hbc positive patterns should be tested for the presence of hbv dna irrespective of their anti - hbs status .\nnevirapine is commonly included in the first line art regimens at most treatment centers in nigeria .\nour study identified only 21 subjects with obi , and all the samples were collected from a single center indicating that results might differ in setting with significant different demographic characteristics .\na main implication of the presently viable data is therefore further emphasizing the need for efficient hbv vaccination programs .\noverall , the present study highlights the need for screening hbv before the initiation of any haart containing anti - hbv regimens in hbv / hiv coinfected patients .\nit necessitates the use of nat for effective laboratory diagnosis of occult hbv infections in hiv positive patients , especially in developing countries where these assays are not widely available .", "answer": "hiv has been known to interfere with the natural history of hepatitis b virus ( hbv ) infection . in this study \n we investigate the prevalence of occult hepatitis b virus infection ( obi ) among hiv - infected individuals in nigeria . \n overall , 1200 archived hiv positive samples were screened for detectable hbsag using rapid technique , in ikole ekiti specialist hospital . \n the hbsag negative samples were tested for hbsag , anti - hbc , and anti - hcv by elisa . \n polymerase chain reaction was used for hbv dna amplification and cd4 counts were analyzed by cytometry . \n nine hundred and eighty of the hiv samples were hbsag negative . \n hbv dna was detected in 21/188 ( 11.2% ) of patients without detectable hbsag . \n cd4 count for the patients ranged from 2 to 2,140 cells/l of blood ( mean = 490 cells/l of blood ) . \n hcv coinfection was detected only in 3/188 ( 1.6% ) of the hiv - infected patients ( p > 0.05 ) . \n twenty - eight ( 29.2% ) of the 96 hiv samples screened were positive for anti - hbc . \n averagely the hbv viral load was < 50 copies / ml in the obi samples examined by quantitative pcr . \n the prevalence of obi was significantly high among hiv - infected patients . \n these findings highlight the significance of nucleic acid testing in hbv diagnosis in hiv patients .", "id": 139} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin clinical practice , paradoxical clinical results that require alternative strategies may be encountered . here\nwe present a case of a patient with results of cardiac catheterization that are incompatible with st segment elevation and elevated cardiac enzymes .\nalthough technologically advanced diagnostic examinations are becoming increasingly available , noninvasive bedside ultrasound examination remains to be indispensable .\nalthough cardiac myxomas are relatively uncommon compared with coronary and valve lesions in the elderly , they are easily diagnosed by basic echocardiography ; this diagnostic test may be the key to solving puzzling presentations and should a part of most cardiac workups .\nstroke is a complication in 10% to 30% of cardiac myxoma patients as found in a case series spanning 20 years in belgium and a 11-year series conducted at the mayo clinic ; no cases of cardiac myxoma in either study had concurrent myocardial infarction .\nforty cases of myxoma - related myocardial infarction were recorded in a systematic review of published data spanning 32 years .\nthis case report shares our experience with a rare case of cardiac myxoma with concurrent stroke and st - elevation myocardial infarction with normal coronary angiography .\nsigned consent from the patient was obtained , and approval was granted by the institutional review board of taipei tzuchi hospital for this case report . a 67-year - old unconscious woman presented to the emergency department of our hospital within 30 minutes of collapsing at an outdoor market\n. she was afebrile with blood pressure of 100/80 mm hg , heart rate of 90 beats per minute , and respiratory rate of 26 breaths per minute on mask oxygen .\non physical examination , the patient displayed grimace in response to painful stimuli , pupils were equal and reactive to light , heart beats were regular without obvious murmurs , breath sounds were coarse without wheezing , abdomen was soft and nontender , urine was clear with adequate output into a foley bag , and legs were warm and nonedematous ; examination was otherwise unremarkable .\nelectrocardiogram showed significant st elevation in the inferior and lateral leads ( figure 1 ) .\nchest x - ray showed lung congestion , minimal effusion in the pericardial and pleural spaces , and a narrow mediastinum . computed tomography of the brain showed no hemorrhage or detectable ischemia . although awaiting cardiac catheterization , she regained consciousness and was able to follow commands and move all extremities . however , severe orthopnea with respiratory distress developed , and she was endotracheally intubated .\nwe then performed echocardiography , which revealed an oscillating round mass measuring 3 3 cm inside the left atrium attached by a pedicle to the interatrial septum that was obstructing inflow through the mitral valve during diastole ( figure 2 ) .\nalthough in the intensive care unit , the patient 's lung edema deteriorated rapidly , resulting in cardiogenic shock that required increased inotropic support and high - setting ventilator support .\nechocardiograph of the oscillating left atrial myxoma ; surgical specimen of the completely resected atrial myxoma .\nthe myxoma was resected en bloc with its pedicle and adjacent interatrial septum ( figure 2 ) .\nataxia was noted during rehabilitation , and magnetic resonance imaging of the brain revealed left cerebellar infarction .\ncardiac atrial myxoma is uncommon , with an estimated incidence of < 0.1% by autopsy series .\noften initially asymptomatic , symptoms arise because of obstructive , embolic , or constitutional events .\na 20-year surgical cohort of cardiac myxoma cases in belgium estimated 65.6% of presenting symptoms to be obstructive and 15.6% to be embolic . as in our case\n, emergent resection may be necessary if cardiogenic shock develops because of mitral valve obstruction .\nechocardiography can readily reveal obstruction by a cardiac myxoma , usually of mitral valve inflow , allowing timely determination of severity and necessity for emergent surgical resection .\nmyxoma - related stroke is relatively more common than myxoma - related myocardial infarction for myxoma - related embolic events . in the aforementioned 20-year myxoma surgical series ,\nbrain ischemia was involved in 15.6% of cases , brain and peripheral artery embolic ischemia in 6.2% , and angina in 3.1% , whereas no cases involved myocardial infarction .\nmyxoma - related coronary artery embolism is rare and much less common than brain embolism .\nestimated incidence of myocardial infarction in cardiac myxoma ranges from close to 0% to as high as 10% if coronary emboli is included .\na review of cardiac myxoma cases spanning 11 years conducted by the mayo clinic found that 12% of cases had image - evident stroke .\ntherefore , coexisting stroke and myocardial infarction , as in our case , are exceedingly unusual .\nmyocardial infarction with normal immediate angiography is rare for cardiac myxoma . in a systematic review of published data from 1970 to 2002 ,\npatent coronary arteries were found only on latent angiography ( performed more than 2 weeks after the initial event ) , but not on immediate angiography .\nnegative latent angiography may be explained by recanalization performed days or weeks after the initial coronary events .\npossible explanations may include rapid and spontaneous recanalization , a washout effect of embolic myxoma fragments or induced thrombi , or compromised hemodynamics because of mitral valve obstruction .\nechocardiography , a noninvasive and portable examination , is often critical for properly identifying the etiology of cardiac conditions such as acute heart failure .\nbasic echocardiography , or focused cardiac ultrasound , is easily learned and often sufficient for detecting intracardiac masses or intrathoracic effusion .\nour case demonstrates the importance of basic echocardiography for optimizing the management of cardiac cases , and supports the recommendation that basic echocardiography be readily available for most cardiac teams or acute care centers .\nour atypical case of normal immediate coronary angiography in myxoma - related myocardial infarction with mitral valve obstruction and multisystem embolism ( heart and brain ) deserves attention because of the rarity of this combination of presentations .\nthe case stresses the value of basic echocardiography in the efficient and effective management of the patient and the importance of including it in most cardiac workups .\nin addition , this experience is a reminder for clinicians to include cardiac myxoma in the differential diagnosis list and to manage it timely if found .\nalthough cardiac myxoma may have unexpected presentations , it can be easily diagnosed by basic echocardiography and should not be missed .\nonce diagnosed , cardiac myxoma requires timely surgical en bloc resection to avoid deterioration resulting from worsening embolism or obstruction .", "answer": "abstractwe present a case of cardiac myxoma with atypical presentations of concurrent stroke and angiography - negative myocardial infarction . \n the case emphasizes the importance of basic echocardiography and timely surgery in the management of cardiac myxoma.an elderly woman presented to the emergency department in an unconscious state . electrocardiogram and \n elevated cardiac enzymes suggested acute myocardial infarction ; however , immediate coronary angiography proved patency . \n basic echocardiography revealed an oscillating left atrial myxoma obstructing inflow through the mitral valve . after regaining consciousness while in the intensive care unit , the patient developed respiratory distress and shock , and emergent en bloc resection was performed . \n ataxia was noted in her postoperative course and multiple small cerebellar infarcts were found on magnetic resonance imaging . after a 1-month period of rehabilitation , \n the patient recovered well and continues to be followed as an outpatient.cardiac myxoma requires timely management and may be missed if not included in the differential diagnoses . \n basic echocardiography , also called focused cardiac ultrasound , may aid in the diagnosing of perplexing cardiac cases .", "id": 140} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiarrhea , including that of parasitic origin , remains one of the most common illnesses among children and , as reported by the world health organization , is one of the major causes of infant and childhood mortality in developing countries .\nintestinal opportunistic parasitic infections are important causes of diarrhea which is a serious health problem in tropical regions .\nare common parasitic causes of human diarrhea with the prevalence rate of 1%3% in the industrialized world and 4%-17% in developing countries . in developed countries , massive cryptosporidium food borne and waterborne outbreaks\nhave been reported because cryptosporidium oocysts are not killed by conventional disinfectants and chlorination . in developing countries\n, cryptosporidium affects mostly children under five years of age and has been reported to be more common in malnourished than in well - nourished children[4 , 5 ] . \n c. parvum\n, a protozoan parasite of the phylum apicomplexa , is an enteric pathogen that causes an acute as well as chronic diarrhea in humans .\nthe human host range is broad and includes people with immunodeficiency , children in developing countries , and outbreaks among immuno - competent individuals . in a healthy adult\n, infection often results in a self - limited diarrheal illness , however , in children of developing countries , cryptosporidiosis can result in persistent diarrhea leading to malnutrition and developmental delays .\nindeed , cryptosporidium is still an under - diagnosed cause of diarrheal illness in children .\nfew reports with relatively small sample sizes are available on the prevalence and clinical presentation of cryptosporidium infection in both immuno - compromised and immune - competent children in iran[713 ] .\nthe purpose of this study was to determine and compare the prevalence of c. parvum infection in children with an acute or persistent diarrhea in isfahan city , central iran .\nthis cross - sectional study was prospectively conducted in three university hospitals in isfahan from august 2007 to june 2008 .\nchildren aged one month to 10 years presenting with acute or persistent diarrhea were visited in each hospital by one of the researchers ( pediatrician ) of the study and were included consecutively .\ndiarrhea was defined as the passage of abnormally liquid or unformed stools at an increased frequency and further defined as acute if lasted < 2 weeks and persistent if lasted for 2 to 4 weeks before admission .\nchildren who had used antiparasitic or antibiotic drugs before admission and also those with known hematologic diseases and immuno - compromised children were excluded from the study . assuming the average prevalence of c. parvum to be 5% according to previous reports , and a margin error of 2% ( difference between estimated and reported prevalence ) and 95% confidence , a sample size of 456 was calculated for determining the overall prevalence of c. parvum .\nfecal samples were collected in sterile plastic bottles and were transported without preservative and arrived in the central laboratory of isfahan city within 24 hours of collection .\nthe oocyst of c. parvum was tested using a modified acid - fast staining method which is a sensitive and specific approach for the identification of cryptosporidium and coccidian oocysts in stools . in this technique ,\nthe oocysts appear as pink to red , spherical to ovoid bodies on a blue or purple background .\nthe study protocol was approved by the ethical committee of isfahan university of medical sciences and consent was obtained from the parents .\nthe chi - square test was used to compare relative frequency of cryptosporidium infection between children with acute and persistent diarrhea .\nindependent t - test was used to compare the mean age between infected and non - infected children .\nduring the study period , 606 children aged one month to 10 years were presented with acute or persistent diarrhea to three university hospitals in isfahan .\nthere were 254 ( 41.9% ) males and 352 ( 58.1% ) females with the mean age of 42.430.0 months .\nacute or persistent diarrhea was present in 422 ( 69.6% ) and 184 ( 30.4% ) of the children , respectively .\ncryptosporidium oocysts were detected in 12.5% ( 23/184 ) of the children with persistent compared to 1.2% ( 5/422 ) of the children with acute diarrhea ; p<0.001 .\nmost ( 89.2% ) of the infected children were under 5 years of age , however , the age difference between the infected and non - infected children was not statistically significant ; p=0.1 . also , there was no significant sex difference between the infected and non - infected children ; p=0.5 ( table 1 ) . \n \ncomparison of infected and non - infected children the age difference between children with acute and persistent diarrhea was not statistically significant ( 43.933.4 vs 38.919.6 months , p=0.06 ) and there was no significant difference between the two sexes ( 248/174 vs 104/80 female / male ratio , p=0.6 ) .\nintestinal parasites are very common in developing countries and cryptosporidium has revealed to be one of the most common parasites .\ncryptosporidium infests the small intestinal epithelium , thereby , results in an accelerated loss of villous enterocytes , leading to severe villous atrophy and a malabsorptive and secretory diarrhea which is the most pronounced clinical feature of the infection .\nother symptoms include dehydration , weight loss , stomach cramp , or pain , fever , nausea , and vomiting .\nthe infectious dose is low and feeding studies have demonstrated that the ingestion of as few as 1030 oocysts can cause infection in healthy persons .\ninfected persons have been reported to shed 1010 oocysts in a single bowel movement and to excrete oocysts for up to 50 days after cessation of diarrhea[16 , 17 ] .\nthere are discrepancies in the prevalence of cryptosporidiosis in children among surveys in different parts of iran .\nthe reported prevalence is from 1.5% in rasht ( northern city of iran ) to 21.4% in shiraz ( southern city of iran)[713 ] .\nthe difference in the reported prevalence may be attributed to differences in study population ( considering age range ) , diagnostic methods , environmental risk factors ( public water supply ) , time of the study ( summer vs winter ) , nutritional status of the children , and other risk factors[6 , 18 , 19 ] .\nin other countries , the rates of cryptosporidiosis are 1%-2% in europe , 0.6%4.3% in north america , and 3%-10.2% in asia , australia , africa , and central and south america .\nseveral methods are available for identification of cryptosporidial oocysts in fecal specimens including modified acid - fast staining which detects oocyst wall , fluorescein - conjugated monoclonal antibody - based detection of oocyst wall antigen , enzyme - linked immunosorbent assay ( elisa ) which detects cryptosporidial antigen and most recently polymerase chain reaction ( pcr ) which detects crytosporidial dna . modified acid - fast stain of a fecal smear has been the gold standard for detecting cryptosporidium oocysts in stool .\nalthough the concentration and staining procedures are time- consuming and also require an experienced microscopist to read the slides , it is inexpensive and allows the detection of other parasites ( eg , isospora and cyclospora ) at the same time .\nhowever , the sensitivity for the detection of cryptosporidium is substantially better with elisa formats or immunofluorescent assays .\npcr method is sensitive , but the cost and tedious methodology have limited its use in the clinical microbiology laboratory .\nregardless of the method used , it is extremely important that the physician remembers to request cryptosporidial testing when stool from a child with diarrheal illness is to be examined for ova and parasites .\nthe results of the present study showed that children with cryptosporidiosis are more likely to present with persistent diarrhea , compared to acute diarrhea . in a report from southeastern iran , hamedi and\nhowever , khalili and colleagues in their study on 171 children found no relationship between type of diarrhea and infection .\nalthough our study did not show significant age difference between the infected and non - infected children , most of the infected children , as expected , were below 5 years old .\nthough humans are susceptible at any time in their lives , the prevalence of cryptosporidiosis is higher in younger children mostly in children aged below 5 years[8 , 10 , 11 ] .\nthe occurrence of high infection rates in younger children might be attributed to their weak immune responses and/or risk of contact with the oocysts . however , more studies are needed to confirm this subject[12 , 18 ] .\nalthough the sample size of the study was large enough , sampling was consecutive and not random .\nhowever , the study was multicenter and we conducted the study through one year , so it is unlikely that season or selection bias affected our results .\nalso we applied the modified acid - fast staining and although it is a sensitive and specific approach for the identification of cryptosporidium , elisa and immunofluorescent assays are more sensitive in this regard .\nwe recommend evaluating children for important risk factors for infection with cryptosporidium , such as nutritional and socioeconomic status , for future studies .\nthe prevalence of cryptosporidiosis in children presenting with persistent diarrhea is considerable and we suggest routine stool examination for cryptosporidium in these children for early diagnosis and treatment to prevent possible complications .\nalso , for control and prevention of this infection , strengthening water quality standards and improving sanitary practices are required .", "answer": "objectivecryptosporidiosis is an important enteric parasitic infection among infants and children in developing countries with significant morbidity and mortality especially among immuno - suppressed individuals . \n the aim of the present study was to estimate the prevalence of enteric cryptosporidiosis in children presenting with diarrhea in isfahan.methodsthis cross - sectional study was conducted from august 2007 to june 2008 in three university hospitals in isfahan . \n children aged 1 month to 10 years presenting with acute or persistent diarrhea were selected consecutively . \n the oocyst of c. parvum was investigated in stool specimens using a modified acid - fast staining method.findingsduring the study period , 606 children ( mean age 42.430.0 months , 58.1% female ) were recruited . \n acute and persistent diarrhea was present in 422 ( 69.6% ) and 184 ( 30.4% ) of the children , respectively . \n twenty eight ( 4.6% ) specimens were oocyst positive . \n the prevalence of cryptosporidium infection was significantly higher in children with persistent diarrhea compared to children with acute diarrhea ( 12.5% vs 1.2% ; p<0.001 ) . \n most of the infected children were under 5 years of age ( 89.2% ) , however , the age difference between infected and non - infected children was not statistically significant . also , there was no significant difference between infected and non - infected children in gender.conclusionthe prevalence of cryptosporidiosis in children presenting with persistent diarrhea is considerable and we suggest routine stool examination for cryptosporidium in this group of children .", "id": 141} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nreinforced surveillance systems aimed at monitoring the introduction of chikv have been implemented in 6 departments in southeastern france , including the var department , where ae .\nalbopictus has spread since its introduction in 2004 , presumably from northern italy ( 4 ) . on august 29 , 2010 ,\na 7-year - old girl ( patient 1 ) with acute febrile syndrome , headache , and abdominal pain sought treatment in the city of frjus ( var ) 1 day after she had returned from rajasthan , india .\ncontinuous chikv circulation in northern india districts has been reported during 20092010 ( www.promedmail.org ) .\nthree weeks after the notification of patient 1 , another young girl ( patient 2 ) experienced clinical symptoms that began on september 18 with fever , arthralgia , backache , headache , and retro - orbital pain .\npatient 2 s physician reported that a young girl ( patient 3 ) , a close friend of her patient , showed clinical symptoms compatible with chikv infection at the same time .\npatient 3 , who lives near patient 1 , had invited patient 2 to spend the night of september 15 at her home .\na serum sample from patient 3 was collected 1 week after onset of fever and monoclonal antibody capture elisa detected high titers of specific anti - chikv immunoglobulin m. the serum sample also showed a weak rt - pcr signal for chikv . given that patients 2 and 3 did not report any recent travel to areas endemic for chikv\nno complications were recorded , but all 3 patients had persistent weakness and joint pain 3 months after the acute phase .\nintensive mosquito control measures , including spraying for adult mosquitoes and destroying breeding sites , were undertaken around the patients residences and areas visited by confirmed case - patients .\nno further cases were found by the active case finding system ( a local physician and laboratories network ) implemented for 45 days after the declaration of the last autochthonous case .\na molecular study of france/2010 chikv strains isolated in frjus obtained from patients 1 ( imported case ) and 2 ( autochthonous case ) was performed .\nviral genomic rna was extracted from chikv grown once in mosquito c6/36 cells and then subjected to rt - pcr amplification by using a set of primers targeting the structural genes of chikv ( 7 ) . paired sequence analysis of the e26k \ne1 junction showed that the 2 france/2010 chikv strains display a divergence rate < 0.05% at the nucleotide level , whereas 100% identity was observed at the amino acid level .\nphylogenetic analysis demonstrated that these viral strains belong to a cluster that is closely related to strains from india within the ecsa lineage ( figure ) .\nthe france/2010 chikv isolate from patient 2 might be derived from an indian strain introduced by patient 1 ( index case ) .\ngenotypes e2 - 211 t , e2 - 312 m , e2 - 386a , 6k-8i , and e1 - 284e that are found in the currently circulating strains belonging to the ecsa lineage were identified in france/2010 chikv isolates ( 2,3,7 ) .\nthese isolates also display the genotype e1 - 211e specifically shared by viral strains belonging to the asian phylogenetic group ( table ) .\nthe residue ala at position e2 - 264 has not been previously described in any chikv strains .\nphylogenetic relationships among chikungunya virus isolates from cases of chikungunya fever in france , based on complete e2 - 6k - e1 nucleotide sequence ( 2,771 nt ) analysis .\nphylogenetic analysis was inferred by using the maximum - likelihood method as implemented in mega version 5 software ( www.megasoftware.net ) .\nthe sequence of the strains from france described in this study has been deposited in genbank ( accession number pending ) ; other sequences were retrieved from genbank .\n* molecular signatures were based on the analysis of complete amino acid sequence e2 - 6k - e1 ( 923 aa ) .\nthe numbering of amino acid positions refers to the african isolate s27 ( genbank access no .\nletters in parentheses after strain names refer to east / central / south africa ( a ) , asia ( b ) and west africa ( c ) phylogroups .\nrecent attention has focused on the predominant role of e1 and e2 proteins in successful chikv infection of the anthropophilic ae .\nvector competence experiments with la runion/2006 chikv isolates demonstrated the importance of the newly acquired e1-ala226val substitution for efficient transmission by ae .\nalbopictus from northern italy and from southeastern france showed disseminated infection rates ranging from 75%90% for chikv strains with e1 - 226v ( 10 ) .\nthe 2 france/2010 chikv strains isolated in frjus have ala at position e1 - 226 ( table ) .\nthe presence of an asp residue at position e2 - 60 , found in most of the ecsa chikv strains , may in part counterbalance the less favorable transmission of e1 - 226a strain in ae .\nalbopictus ( table ) . the thr residue at position e2 - 211 potentiates the infectivity of chikv in ae .\nthe presence of e2 - 211 t in chikv isolates from france underlines the risk for emergence of a fully adapted viral variant if the e1 - 226v genotype was selected during continuous transmission within ae .\nthe efficient chikv transmission in italy and southeastern france sheds new light on its dissemination potential in europe from 1 index case , regardless of the viral genetic background and mosquito species in the region of origin of the imported chikv ( 1,10,11 ) . in emerging regions , such as italy and runion island , where the seroprevalence in the population was < 50%\nhowever , > 2 years passed since the end of the epidemic in runion island before a local transmission of chikv was again detected . in europe\nwhere sylvatic cycles are absent , vertical transmission may participate in the maintenance and/or cyclic reemergences of chikv .\nalbopictus that may have more efficient vertical transmission than mosquito populations in eastern italy and tropical regions ( 11,12 ) . in 2010 ,\nsoutheastern france faced the concomitant emergences of dengue virus ( denv ) and chikv ( 13 ) . for each of these viruses ,\nonly 2 autochthonous infections were confirmed , which suggests that rapid detection and control measures implemented around imported and autochthonous cases have been efficient .\na recent report mentioned the dual emergence of chikv and denv in southeastern france and urged the implementation of specific surveillance and response measures to reduce the risk for arbovirus emergence ( 14 ) . since 2006 , a specific chikungunya / dengue national preparation and response plan based on rapid detection and investigation of imported and suspected autochthonous cases , mosquito control measures , and efficiency evaluation in the treated areas has been activated from may through november and then modified after annual debriefing meetings involving all partners . in 2010 , this model proved to be well adapted to the early detection and control of chikv and denv .\nalbopictus mosquitoes and the successful emergence of chikv in italy and france , reinforced surveillance and response to chikv and denv dissemination should become a higher priority in europe ( 15 ) .", "answer": "in september 2010 , autochthonous transmission of chikungunya virus was recorded in southeastern france , where the aedes albopictus mosquito vector is present . \n sequence analysis of the viral genomes of imported and autochthonous isolates indicated new features for the potential emergence and spread of the virus in europe .", "id": 142} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute appendicitis and typhlitis are the most common causes of gastrointestinal surgical complications in children undergoing chemotherapy for acute leukemia with reported incidences of 0.54.4% and 1.76.7% respectively [ 14 ]\n. early diagnosis by radiologic imaging is essential as appendicitis usually requires emergent surgical management .\nin such situations , the clinician must also balance the risk of further immunosuppression and chemotherapeutic toxicities with the risk of delaying appropriate leukemia therapy .\na retrospective case review of all children 18 years of age diagnosed with acute leukemia at our institution between january 2002 and december 2011 was performed after obtaining institutional irb approval . amongst 154 children eligible , three ( 1.9% ) patients\nappendicitis was diagnosed based on clinical , imaging and histologic findings . a 17-year - old girl with relapsed acute myeloid leukemia ( aml ) developed nausea , vomiting , mild lower abdominal pain and breakthrough menstrual bleeding three days into hospitalization for induction chemotherapy with cytarabine and mitoxantrone . on day fifteen\n, her abdominal pain localized to the right lower quadrant ( rlq ) followed by fevers three days later .\neventually , she underwent a matched unrelated donor bone marrow transplant ( bmt ) and was in remission at seven - year follow - up . an 18-year - old girl with relapsed leukemia consistent with acute lymphoblastic leukemia ( all )\nin addition to intermittent nausea , vomiting , and diarrhea , significant rlq pain with fever on hospital day nineteen ( maximum 39.5 c ) prompted an abdominal ct scan that showed an edematous , thickened appendix with surrounding inflammation .\nshe underwent an emergent laparoscopic appendectomy and pathology revealed a non - perforated appendix with inflammatory infiltrate without leukemic involvement .\nshe eventually underwent a matched related donor bmt and was in remission at three - year follow - up . a 10-year - old girl presented with generalized myalgias ,\nfevers and gingival hypertrophy and was diagnosed with primary aml with maturation ( fab : m2 ) .\ncytogenetics revealed no clonal abnormalities and aml panel fluorescent in - situ hybridization studies were normal . during hospitalization for induction chemotherapy , after five days of decitabine ( 20 mg / m / day ) on study and one dose of systemic cytarabine ( 100 mg / m / dose ) , she developed abdominal pain with high - grade fevers ( maximum 40.1 c ) .\nabdominal ct scan demonstrated numerous fluid - filled edematous bowel loops with enhancement , fluid collections , and findings consistent with an inflamed appendix with fecalith .\nan emergent laparotomy revealed gross soilage of the abdomen due to a perforated necrotic appendix eroding into the distal ileum and colon necessitating a diverting ileostomy and partial right colectomy . at the time of surgery , her absolute neutrophil count ( anc ) was 4.0810/l .\nhistopathology revealed immature myeloid cells , consistent with leukemic involvement of the appendix , in addition to inflammatory infiltrates .\nparenteral antimicrobial therapy was continued for approximately 6 weeks during which chemotherapy was held to avoid further immunosuppression .\npacked red blood cell and platelet transfusions were required within the first postoperative week following which no transfusion support was needed until resumption of standard chemotherapy about 8 weeks later . during this 8 week period ,\nher anc fluctuated from 0.64 to 5.3310/l with counts of < 110/l noted only on 2 occasions at 24 days and 37 days from surgery .\nshe did not experience sustained neutropenia and , hence , no significant issues were noted during this 8 week period .\nbone marrow biopsy twenty - five days from initiation of induction chemotherapy showed no morphologic features of aml . despite receiving only a short course of decitabine and one dose of systemic cytarabine , she achieved and maintained complete remission until resumption of standard intensive chemotherapy .\na 17-year - old girl with relapsed acute myeloid leukemia ( aml ) developed nausea , vomiting , mild lower abdominal pain and breakthrough menstrual bleeding three days into hospitalization for induction chemotherapy with cytarabine and mitoxantrone . on day fifteen , her abdominal pain localized to the right lower quadrant ( rlq ) followed by fevers three days later .\neventually , she underwent a matched unrelated donor bone marrow transplant ( bmt ) and was in remission at seven - year follow - up .\nan 18-year - old girl with relapsed leukemia consistent with acute lymphoblastic leukemia ( all ) was hospitalized for chemotherapy with cytarabine and clofarabine .\nin addition to intermittent nausea , vomiting , and diarrhea , significant rlq pain with fever on hospital day nineteen ( maximum 39.5 c ) prompted an abdominal ct scan that showed an edematous , thickened appendix with surrounding inflammation .\nshe underwent an emergent laparoscopic appendectomy and pathology revealed a non - perforated appendix with inflammatory infiltrate without leukemic involvement .\nshe eventually underwent a matched related donor bmt and was in remission at three - year follow - up .\na 10-year - old girl presented with generalized myalgias , fevers and gingival hypertrophy and was diagnosed with primary aml with maturation ( fab : m2 ) .\ncytogenetics revealed no clonal abnormalities and aml panel fluorescent in - situ hybridization studies were normal . during hospitalization for induction chemotherapy , after five days of decitabine ( 20 mg / m / day ) on study and one dose of systemic cytarabine ( 100 mg / m / dose ) , she developed abdominal pain with high - grade fevers ( maximum 40.1 c ) .\nabdominal ct scan demonstrated numerous fluid - filled edematous bowel loops with enhancement , fluid collections , and findings consistent with an inflamed appendix with fecalith .\nan emergent laparotomy revealed gross soilage of the abdomen due to a perforated necrotic appendix eroding into the distal ileum and colon necessitating a diverting ileostomy and partial right colectomy . at the time of surgery , her absolute neutrophil count ( anc ) was 4.0810/l .\nhistopathology revealed immature myeloid cells , consistent with leukemic involvement of the appendix , in addition to inflammatory infiltrates .\nparenteral antimicrobial therapy was continued for approximately 6 weeks during which chemotherapy was held to avoid further immunosuppression .\npacked red blood cell and platelet transfusions were required within the first postoperative week following which no transfusion support was needed until resumption of standard chemotherapy about 8 weeks later . during this 8 week period , her anc fluctuated from 0.64 to 5.3310/l with counts of < 110/l noted only on 2 occasions at 24 days and 37 days from surgery .\nshe did not experience sustained neutropenia and , hence , no significant issues were noted during this 8 week period .\nbone marrow biopsy twenty - five days from initiation of induction chemotherapy showed no morphologic features of aml .\ndespite receiving only a short course of decitabine and one dose of systemic cytarabine , she achieved and maintained complete remission until resumption of standard intensive chemotherapy .\nappendicitis is seen in the general population with a lifetime cumulative incidence rate of 9% .\nour calculated incidence rate of appendicitis in the setting of acute leukemia ( 1.9% ) correlates with the reported incidence of 0.54.4% .\nleukemic involvement of the gastrointestinal tract as well as the treatment thereof can compromise the structural integrity of the intestinal wall .\nmoreover , atypical presentations of appendicitis are common in immunocompromised patients due to underlying malignancy and ongoing chemotherapy .\nearly symptoms such as nausea , vomiting , abdominal pain , and diarrhea are non - specific and may be attributed to chemotherapy side effects delaying accurate diagnosis .\nin addition , typhlitis often mimics the classic presentation of appendicitis , and therefore imaging must be performed to distinguish these entities as their management approaches differ .\nalthough successful conservative management has been reported , the majority require surgical intervention to avoid devastating complications .\nseveral groups have demonstrated safety and efficacy of surgical intervention and operative management may also shorten the length of hospital stay compared to nonoperative management . in our cohort ,\nall three patients were operated upon emergently and all of them including the patient with appendiceal perforation and leukemic infiltration tolerated surgery well . for the treating clinician\n, the bigger conundrum is the need to suspend chemotherapeutic treatment during life - threatening infections such as appendicitis , while weighing in a heightened risk for uncontrolled leukemic cell proliferation . alternatively ,\nother anti - leukemic agents such as decitabine have been demonstrated to be effective and well - tolerated in adults with myelodysplastic syndrome , high risk aml , as well as those ineligible for standard chemotherapy due to extensive comorbidities such as the elderly [ 1113 ] .\ndecitabine ( 5-aza-2-deoxycytidine ) is a cytosine nucleoside analog that after phosphorylation directly incorporates into dna resulting in inhibition of dna methyltransferases .\nthe resulting dna hypomethylation causes reversal of abnormal epigenetic silencing of genes critical to normal cellular differentiation , proliferation , and normal cellular life processes such as apoptosis .\nit has minimal toxicity and hence is favored in patients who are unable to tolerate standard chemotherapeutic regimens .\nour third patient was enrolled in a trial utilizing a short five - day course of decitabine prior to intensive chemotherapy with cytarabine , daunorubicin and etoposide .\nshe achieved and remained in remission with one cycle of decitabine and one dose of cytarabine without significant hematologic toxicities despite considerable delay in resumption of chemotherapy due to overwhelming infection .\nlow - dose decitabine ( 20 mg / m / day for 10 days given every 4 weeks ) has demonstrated promising results in children with very high risk relapsed/ refractory aml in whom other treatment options had been exhausted .\nthree out of eight patients had a complete response , with best responses noted after a median of 2.5 cycles . despite significant comorbidities , decitabine monotherapy demonstrated minimal toxicity .\nrecently , sequential treatment with decitabine and cytarabine was found to be more effective than cytarabine alone in xenograft models of childhood aml .\nrelative to studies with heavily pre - treated patients , our patient was chemotherapy naive and had minimal hematologic or other toxicities secondary to chemotherapy .\ngiven the favorable toxicity profile and efficacy in childhood aml , we suggest that decitabine may serve as a bridging anti - leukemic agent during serious illness and reduce risk of recurrence secondary to prolonged treatment delays .\noverall , managing concurrent malignancy and critical illness is a delicate balance , one in which decitabine may play a pivotal role ; however further clinical trials are needed .", "answer": "acute appendicitis in children with acute leukemia is uncommon and often recognized late . \n immunocompromised host state coupled with the importance of avoiding treatment delays makes management additionally challenging . \n leukemic infiltration of the appendix though rare must also be considered . \n although successful conservative management has been reported , surgical intervention is required in most cases . \n we present our experience with acute appendicitis in children with acute leukemia and a case of complete remission of acute myeloid leukemia with a short course of decitabine . \n decitabine may serve as bridging therapy in critically ill patients who are unable to undergo intensive chemotherapy .", "id": 143} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nInvestigation of an F-18 oxytocin receptor selective ligand via PET imaging\n\nPaper sections:\n\nOxytocin was the first endocrine system hormone to be synthesized in the laboratory, and has been studied extensively for its role in the induction of labor and the milk ejection reflex.1 More recently, research foci have been directed toward the role of oxytocin and the oxytocin receptor (OTR) in the regulation of psychosocial behavior.2\u201310 In addition to being implicated in modulating maternal nurturing and mother\u2013infant bonding, pair bonding, social recognition, increased eye-to-eye contact, trust and empathy, the oxytocin system has also been investigated in relation to disorders characterized by disruption in social behavior, including autism spectrum disorders.11\u201317 While the bulk of the research conducted with the oxytocin system in humans has been limited to experimental paradigms involving administration of oxytocin followed by behavior monitoring, methodologies implemented for investigating OTR within the brain have been limited to post-mortem receptor autoradiography, in situ hybridization, and gene association studies.12,13,18\u201321 The development of a methodology permitting the quantification of OTR in the living brain would represent a significant advance in this area of research. Our goal is to develop a positron-emitting small molecule with high affinity and selectivity for the human and primate OTR to enable non-invasive correlations between neural OTR densities and behavior via in vivo positron emission tomography (PET). In addition to this goal, we are simultaneously seeking to discover new candidate pharmaceuticals which may prove useful in reaching OTR specifically within the brain or the periphery for the purpose of potentially alleviating and/or investigating symptoms associated with social behavior disorders. We report here the synthesis, radiosynthesis, and PET imaging evaluation of one of our lead candidate compounds meeting these criteria.
We have recently reported progress in the development of OTR selective ligands bearing radioactive isotopes with some bearing structural similarity to the lead candidate described here.22,23 These molecules were found to either not penetrate the blood\u2013brain barrier or have high affinity for the p-glycoprotein pump which prevented their retention within the brain. We concluded that the lack of a hydrogen bond donor may have been the cause for lack of brain penetration or retention. Therefore, we proceeded to modify the structure by eliminating the methyl sulfonyl group of our former lead candidate, 2, to generate a compound bearing a free amine to act as a hydrogen bond donor, 1 (Fig. 1). The synthetic route was derived from a precursor in our previously reported synthetic pathway, 3, and is outlined in Scheme 122 The free amine of 3 was protected using di-tert-butyl dicarbonate to generate 4. The phenol position of 4 was then alkylated using 1-bromo-2-fluoroethane to provide the fluoroethoxy moiety of 5. A deprotection using 2 M HCl in ether then resulted in the target molecule, 1, as a hydrochloride salt. Further synthetic details and characterizations are provided in the Supplementary data.
To determine if the structural modification resulted in any loss of biological properties, 1 was subjected to in vitro competitive binding assays using cell lines expressing human oxytocin and all known vasopressin receptor subtypes (V1aR, V1bR, and V2R). The results of these assays are displayed in Table 1 with data for 2 obtained from our previously reported study.22 These data indicate the removal of the methyl sulfonyl group actually resulted in a slight improvement of the biological properties. Having a Ki value of 15 nM for the OTR, 1 matched the binding affinity of 2. While the binding affinity of 1 for the V1aR slightly increased, the binding affinity for the V2R decreased significantly in comparison to 2, thus making it slightly more selective overall. Further in vitro binding assays were also performed on 88 other human G-protein coupled receptors (GPCR) in a screen to determine if 1 had affinity for these other receptors. Table 2 contains the results of the screen in which 7 other GPCR had modest to mild affinity for 1, none of which would be expected to display significant uptake during a PET scan. The most notable binding affinity was found in the alpha-1A subtype of the adrenergic receptor and the 6 subtype of the 5-hydroxytryptophan receptor (5-HT6) having a Ki values of 82 nM and 187 nM, respectively. Although these Ki values for the non-target receptors are not believed to be optimal for PET imaging, they would present an issue if 1 was to be considered for pharmaceutical development.
Having good binding affinity and selectivity, the F-18 analogue of 1 was generated for further investigation. The synthetic route to [18F]1 is outlined in Scheme 2. The Boc-protected amine 4 was alkylated with ethane-1,2-diyl bis(4-methylbenzenesulfonate) to generate our tosylate precursor 6. Radiolabeling was then conducted in a CTI-Seimens Chemistry process Control Unit (CPCU) to perform SN2 substitution using the cryptand ligated K222\n18F followed by removal of the Boc-protecting group with 1 M HCl. The crude radioactive mixture was eluted from the CPCU unit with a 7 ml solution of ethanol:water:triethylamine (50:50:0.1). Solid phase extraction was then performed to remove excess acid prior to HPLC purification. The extracted mixture was then purified via HPLC and concentrated into a dose form (15 ml solution of 10% ethanol in saline) via solid phase extraction and passed through 1 and 0.2 lm filters using high argon pressure. A dose would normally be prepared in 120 min from the start of synthesis and result in approximately 19% uncorrected yields of [18F]1 with a specific activity greater than 10 Ci/\u00b5mol. Radiochemical purity was greater than 99.9%. A representative analytical HPLC graph is shown in Figure 2.
To gauge the probability of brain penetration, the log P7.4 was determined to be 1.57 using previously reported methods. This lipophilicity measurement is within the range of 1\u20133 estimated to be the calculated optimal range for penetration of the blood brain barrier.24 To evaluate brain penetration in vivo, PET studies were first performed using female 180\u2013200 g Sprague\u2013Dawley rats (n = 4) in the same manner as our previously reported study.22,25\nFigure 3 contains representative time activity curves generated from [18F]1 distribution which compares the muscle tissue uptake with whole brain uptake. As can be seen in the graph, there is a burst of activity into the brain at the beginning of the scan which clears after 20 min post injection. Therefore, the first 20 min of the scan were summed to analyze brain uptake. Figure 4 contains representative images of [18F]1 over the first 20 min time span post injection. Uptake appears to be located at areas in and around the cerebral ventricles. However, it is difficult to make a conclusive determination of the exact areas of uptake in the rat due to the size of the subject, small areas of OTR binding in the rat brain, limits of resolution of the PET scanner, and limited time of retained uptake.
To further evaluate [18F]1 in a model which would better represent a human and should be large enough to detect regions of OTR binding with a PET scanner, PET imaging was conducted using [18F]1 in a cynomolgus monkey model. Three types of studies were performed to evaluate the tracer and its distribution within the brain, a baseline scan in which only the tracer was injected, a blocking scan (5 mg/kg of the cold standard was administered 30 min prior to the tracer), and a chase scan (5 mg/kg of cold standard was administered 45 min after the tracer). These procedures were performed on a subject anesthetized with Telazol (3 mg/kg; i.m.) and maintained on a 1\u20132% isoflurane in pure oxygen mixture while intubated and placed on a ventilator throughout the imaging procedure. A 15 min transmission scan was performed using a germanium- 68 point source to provide attenuation correction. Approximately 5 mCi of [18F]1 was then administered at the start of the emission scan and scanning continued for 2 h. For blocking and chase studies, 5 mg/kg of 1 was administered 30 min prior to [18F]1 injection or 45 min after [18F]1 injection, respectively, via a slow bolus injection.
Figure 5a\u2013c contains images obtained from the sum of the 2 h baseline scan and arrows indicate the uptake found primarily in the ventricles within the brain. One possible site of radiotracer binding within the ventricles is the choroid plexus, which is a highly vascularized network of structures within the ventricles of the brain which synthesizes and recycles cerebrospinal fluid (CSF). The time activity curves of the standard uptake values (SUV) for the ventricular lining, the whole brain, and the muscle tissue obtained from the baseline scan are shown in Figure 6a. The graph suggests significant amounts of [18F]1 reach the brain during the first 500 s of the scan, but as can seen by the concentration of [18F]1 in the ventricular lining during the same timeframe, it could be deduced to account for the bulk of brain activity detected. Therefore, no significant accumulation of the ligand was detected in any sites within the brain. Thus, it could be deduced that [18F]1 did not penetrate the extracellular space of the brain, and only reached the vasculature and the choroid plexus. As can be seen in Figure 5d which sums up the first 15 min of the scan, there is uptake observed at the middle cerebral artery in the sulcus of the outer region of the cerebral cortex near the insula. This may explain the increase in whole brain uptake during the first 500 s of the scan, although we cannot rule out accumulation in the CSF of this region. The time activity curve of the choroid plexus/ventricular lining in Figure 5a clearly demonstrates that [18F]1 binds strongly in this area. Although there have been reports of vasopressin 1a and alpha-1A adrenergic receptors in this region, there are have been no reports of OTR in the choroid plexus.26
To verify if the observed [18F]1 uptake was due to binding to a saturable protein on the cerebral ventricles, blocking and chase scans were performed in which 5 mg/kg of the cold standard, 1, was administered 30 min prior to [18F]1 (blocking) or 45 min post injection of [18F]1 (chase). The comparable time\u2013activity curves are shown in Figure 6b and c, respectively. The blocking study resulted in an increase of overall brain activity, primarily in the region of the choroid plexus. The images obtained were nearly identical to those obtained from the baseline scan and are not shown. The observed increase of [18F]1 after blocking is thought to be due to the blocking of peripheral OTR and perhaps the mild affinity 1 has for the alpha-1 adrenergic receptor (there is a vast distribution of these type of receptors in the periphery). Once the majority of these receptors are blocked in the periphery, it allowed more tracer to become available in the blood, thus increasing the overall activity concentrations in the choroid plexus and vasculature. The inability of 1 to block the uptake of [18F]1 in the choroid plexus would suggest that the uptake is not specific to a saturable protein. However, the chase study afforded completely opposite results. In the chase study, the uptake within the choroid plexus was completely removed after administration of 1 by the end of the remaining hour and 15 min of scan time. When the summed images from the final 30 min of both the baseline and chase scans are directly compared (Fig. 7), it is clearly evident [18F]1 is completely removed by the addition of 1. These results suggest that 1 has some type of affinity equilibrium within the choroid plexus that shifts when additional amounts of 1 are administered. It should be noted that previously investigated PET imaging studies using pharmaceutical derivatives, including our studies with a completely different OTR selective molecule, have shown to have uptake in the choroid plexus region; the phenomenon is not unique to 1.23,27,28
In summary, a very selective OTR ligand, 1, has been investigated in vitro with receptor binding assays and in vivo via synthesis of its positron emitting analogue, [18F]1, and PET. Brain penetration of [18F]1 may be present in the rat, but appears to be limited to the choroid plexus area in both the cynomolgus macaque and the rat. In the cynomolgus monkey, brain penetration appears to be negligible except for specific uptake within the choroid plexus. Neither PET scan suggested [18F]1 will be useful for detecting OTR in vivo. It is possible that the densities of OTR in the cynomolgus monkey model are not high enough to afford a signal via PET using a biomarker with a Ki affinity greater than 1 nM, or that they even do not exist. Indeed, to date, inconclusive results have been reported regarding specific OTR binding in the rhesus macaque brain29 (Young, LJ and Freeman, SM unpublished data). By contrast, we and others have confirmed that the common marmoset has high densities of OTR in the nucleus accumbens.19 Therefore, we will be conducting future investigations utilizing the common marmoset as the model system. We will continue to perform structure/activity studies with derivatives of this candidate compound to increase brain penetrance, increase affinity for OTR will maintaining selectivity, and eliminate binding to the cerebral ventricles.
", "answer": "The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin- 2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vivo via PET imaging using rat and cynomolgus monkey models. PET imaging studies in female Sprague\\xe2\\x80\\x93Dawley rats suggested [F-18]1 reached the brain and accumulated in various regions of the brain, but washed out too rapidly for adequate quantification and localization. In vivo PET imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain penetration while specific uptake of radioactivity significantly accumulated within the vasculature of the cerebral ventricles in areas representative of the choroid plexus.", "id": 144} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunicystic ameloblastoma ( ua ) was first described by robinson and martinez in 1977 as a special type of ameloblastoma .\nua usually appears very similar to a non - neoplastic odontogenic cyst and is frequently clinically misdiagnosed as dentigerous cyst and odontogenic keratocyst hence , histological confirmation is mandatory from the management point of view .\nthis report highlights the importance of clinical and radiographic features in the diagnosis and management of ua in a 5-year - old boy .\na 5-year - old boy presented to our unit center for dental education and research , all india institute of medical sciences , new delhi , india with a painless hard swelling in the lower chin region of 3 months duration .\nswelling was found to be approximately 2 cm 2 cm in size , overlying skin was normal in color and texture with no evidence of sinus / fistula .\nswelling was non - tender , non - pulsatile , bony hard , non - fluctuant , non - compressible on palpation with expansion of both , buccal as well as lingual cortical plates and aspiration from the swelling yielded cystic color fluid .\npanoramic radiographic revealed that unilocular well - defined radiolucent lesion extending from lower deciduous first mandibular molar to right lower canine with evidence of roots resorption [ figure 1 ] .\npre - operative panoramic radiograph showing radiolucent lesion in the right side of the mandible and resorption of the roots of the teeth on the basis of lingual cortical bone expansion , presence of cystic fluid on aspiration and evident of root resorption of the teeth in the panorex , we made the provisional diagnosis of ua .\nenucleation of the cyst with extraction of the involved teeth followed by application of carnoy 's solution for 3 min over the cavity was planned under general anesthesia ( ga ) .\nhistopathology report of the specimen revealed that type 1 ua as per the histological criteria defined by ackerman et al .\n( a ) discrete epithelial lines in a connective tissue stroma ( h and e , 10 ) , ( b ) discrete follicles with a similarity to the stellate reticulum of enamel with a varying quantity of connective tissue stroma.(h and e , 40 ) patient has been on regular follow - up since 2 years , patient is doing well with no signs of recurrence [ figure 3 ] . post - operative panoramic radiograph showing bone regeneration in the affected area and movement of tooth buds into the regenerated bone at 2 years follow - up period\nameloblastoma is rare before the age of 10 years . according to statistical analysis of 1036 cases of ameloblastoma collected from the literature by small and waldron\nthe ua is considered a variant of the solid or multicystic ameloblastoma , accounting for 6% to 15% of all intra osseous ameloblastomas .\npresence of lingual cortical plate expansion , cystic fluid on aspiration and presence of root resorption of teeth in panoramic radiograph helped us in making the preoperative diagnosis of ua over the dentigerous cyst without incisional biopsy ( which requires ga in the child ) .\nhistopathological features of the tumor showed type 1 ( tumor confined to the luminal surface of the cyst ) ua as per the histological criteria defined by ackerman et al .\ntreatment modality of ua is being divided into following types - enucleation alone yielded the highest recurrence rate among all treatments ( 30.5% ) .\na more conservative approach is enucleation with application of carnoy 's solution and the extraction of closely related adjacent teeth has resulted in a recurrence rate of 16% .\nthe success of the application of carnoy 's solution after enucleation was thought to be due to both its penetration and fixation action .\nthe usual practice is to apply the solution with cotton applicators or ribbon gauze for 3 - 5 min , rinse the bony cavity .\nthe recurrence rate could even lower than reported , if the closely related teeth with tumor are extracted .\nbecause in an attempt to preserve the tooth without damage , tumor remnants may be left around the tooth apex or root and these may lead to recurrence we carried out the same procedure in the case i.e. enucleation followed by application of carnoy 's solution for 3 min , extraction of all involved teeth and close follow - up .\nsecond surgery ( i.e. incisional biopsy followed by definitive treatment ) under ga in the child was not required due to proper preoperative planning of the case . at 2 years", "answer": "unicystic ameloblastoma rarely seen in first decade of life . \n this tumour usually appears very similar to a non - neoplastic odontogenic cyst and is frequently clinically misdiagnosed as dentigerous cyst . \n the distinction from dentigerous cyst is important as unicystic ameloblastoma ( ua ) unlike dentigerous cyst needs different treatment approach and long term follow - up due to its chances of recurrence . \n this report highlights the importance of clinical examination in the diagnosis and management of ua in a 5 year old boy .", "id": 145} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncryptorchidism , defined as the absence of at least one testis in the scrotum , is a frequent condition in the pediatric population .\nit affects up to 9% of full - term newborns and up to 1.5% of 1-year - old boys .\nthe most common location for an undescended testicle is just outside the external ring ( suprascrotal ) , followed by the inguinal canal followed by the abdomen .\ncryptorchidism occurs more commonly among patients with congenital disorders of testosterone secretion or action , secondary hypogonadism , testosterone biosynthetic defects , or insensitivity syndromes , abdominal wall defects , neural tube defects , cerebral palsy , and various genetic syndromes ( e.g. , trisomy 18 , trisomy 13 , noonan syndrome , prader - willi syndrome , and laurence - moon - biedl syndrome ) .\nrathke cleft cysts ( rccs ) are benign , epithelium - lined sellar and suprasellar cysts believed to originate from remnants of the rathke pouch lying between the pars anterior and the pars intermedia of the pituitary gland .\nthey are usually asymptomatic and are discovered incidentally , when radiographic or necropsy findings are reviewed .\nsymptomatic rccs are uncommon , but cysts can enlarge and cause symptoms secondary to compression of the pituitary gland , pituitary stalk , optic chiasm , or hypothalamus .\natypical presentations for rcc include abscess formation within the cyst , aseptic meningitis or entirely suprasellar rcc .\ndistinction among these remains a difficult preoperative problem , because the symptoms , signs , and biochemical and radiographic features of these lesions can mimic each other .\nhere , we report a rare case of entirely suprasellar rathke 's cleft cyst ( rcc ) in a 4.5-year old child causing hypopituitarism , who presented to us with bilateral cryptorchidism .\nalthough till date , a few cases of symptomatic rccs have been reported in world literature , the condition continues to remain largely unknown to practicing clinicians .\nthe current report intends to draw attention towards hypopituitarism as one of the etiology of cryptorchidism . to the best of our knowledge ,\nthis is the first case of entirely suprasellar rcc presenting in a child with cryptorchidism to be reported from world literature .\na 4.5-year - old boy presented to the pediatric surgery department with bilateral undescended testes for which surgery was planned . upon evaluation for short stature at the department of endocrinology , he was found to be born to nonconsanguineous parents , at full term by normal vaginal delivery ; there was no history of prolonged labor or birth asphyxia and his birth weight was 2.5 kg .\nmother noticed bilateral undescended testes at the time of delivery , but was reassured by the doctor that testes would descend subsequently .\nthere was no history of seizures or prolonged jaundice in the neonatal period , but his motor and mental milestones were delayed .\nhe remained shorter than his peers and his sister who is 2 years younger is taller than him .\nthere was no history of chronic systemic disease , hypothyroidism , or features suggestive of raised intracranial pressure . on examination ,\nhis height is 84 cm ( <3 percentile ) , upper to lower segment ratio is 0.9 [ figure 1 ] , standard deviation score was 4 , weight was 13 kg , and head circumference was 51 cm .\nhe had frontal bossing , doll - like facies , central obesity , micropenis with stretched penile length of 2 cm , and both gonads were palpable in suprascrotal area with a poorly developed empty scrotal sac .\ninvestigations revealed a hemoglobin of 13.6 g% ( 11 - 15 ) , total lymphocyte count of 5,600/mm ( 4 - 11,000 ) , erythrocyte sedimentation rate of 15 ( 5 - 20 ) , random blood sugar of 94 mg% ( 90 - 130 ) , creatinine 0.8 mg / dl ( 0.6 - 1.5 ) , free thyroxine ( t4)-0.9 ng / ml ( 0.93 - 1.7 ) , thyroid stimulating hormone ( tsh)-7.27 miu / ml ( 0.3 - 5.5 ) , bone age-1 year , basal cortisol-13.76 g / dl ( 8 - 20 ) , follicle stimulating hormone ( fsh)-0.63 miu / dl ( 1.5 - 10.2 ) , luteinizing hormone ( lh)-0.1 miu / dl ( 1.9 - 12 ) , testosterone basal 0.025 ng / ml ( 3 - 6.5 ) , stimulated testosterone with human chorionic gonadotropin ( hcg ) was 0.68 ng / ml ( suggestive of normally functioning testes ) , and insulin - like growth factor 1 ( igf-1 ) was undetectable .\nradiological evaluation revealed bilateral suprascrotal testes in ultrasound abdomen , a 3.8 3.6 cm suprasellar cystic lesion with compressed pituitary gland in magnetic resonance imaging ( mri ) brain [ figures 2 and 3 ] , which was hypointense on t1 and hyperintense on t2 images suggestive of cystic craniopharyngioma or rathke 's cyst .\nchild did not cooperate for an accurate visual field examination , but grossly he had some degree of visual impairment in left eye .\nurine output and fluid input both were approximately 1 l. magnetic resonance imaging ( mri ) sagittal section is showing suprasellar rathke 's cleft cyst ( rcc ) with normal compressed pituitary mri coronal section is showing suprasellar rcc child was subsequently treated with levothyroxine replacement in view of secondary hypothyroidism .\nafter 4 weeks ( with the normalization of t4 levels ) , he underwent right frontotemporal orbitozygomatic craniotomy , marsupialization of suprasellar cyst along with biopsy .\nbiopsy revealed a single - cell layered , cuboidal epithelium , suggesting a rathke 's cleft cyst .\nso the final diagnosis was rathke 's cleft cyst with hypopituitarism . at 6 and 12\nweeks after surgery , child was reevaluated for pituitary function , which revealed persistent secondary hypothyroidism and low igf-1 levels suggestive of growth hormone deficiency .\nlevothyroxine was reinstituted followed by initiation of growth hormone replacement along with 5 week hcg therapy ( intramuscular ( i m ) 1,000 iu twice a week ) .\nrccs are usually located in an intrasellar or combined intra- and suprasellar location , between the pars anterior and the pars intermedia of the pituitary gland ; they are assumed to be benign remnants of the craniopharyngeal duct , which is part of rathke 's pouch .\nthe pars tuberalis of the pituitary gland which lies above the diaphragma sellae , is also derived from rathke 's pouch , and is the site of origin of entirely suprasellar rccs .\nmajority of the rcc are asymptomatic . if the normal involution of rathke 's pouch fails to occur , the resulting rcc may increase in size by accumulation of cyst fluid and compress the surrounding structures with ensuing headache , visual problems , and hypopituitarism .\nentirely suprasellar symptomatic rccs with normal sella turcica are exceptionally rare and very few case reports are available in world literature .\nfurther , rcc presenting at such a young age with hypopituitarism has not been reported till date .\ntesticular descent occurs in two phases , comprising of transabdominal and inguinoscrotal descent , which occur approximately during the first and last thirds of gestation , respectively .\nkey anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the craniosuspensory ligament and a thickening of the gubernaculum .\nandrogens play a role in both these processes , particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent .\nthe thickening of the gubernaculum , a process crucial for anchoring the testis to the inguinal region is controlled by insulin - like 3 peptide ( insl3 ) and its g protein coupled receptor ( great ) . in turn , this insl3 is controlled by hcg and lh .\neven though surgical management is the cornerstone of treatment for cryptorchidism , medical treatment can be effective in the above mentioned endocrine disorders and it is prudent to give a trial before resorting to orchiopexy .\navailable agents are gonadotropin releasing hormone ( gnrh ) or hcg injections that produce a significant rise in local testosterone levels ; thereby facilitating testicular descent .\ncommonly used agent is hcg and there are many protocols for the use of hcg .\none such protocol is the administration of 1,000 - 2,500 iu two times per week intramuscularly for 4 - 5 weeks .\nwhatever protocol is used , the likelihood of success is greatest in the most distal true undescended testicles .\ncomplete success was defined as full descent of the testicle into the scrotum and needs assessment between 8 weeks and 6 months after the completion of treatment .\nthese studies have reported temporary virilizing side effects , including increased penile length , erections , and testicular enlargement associated with hormonal treatment .\nrcc causing a pressure effect on pituitary with subsequent inhibitory effect on the release of fsh , lh , growth hormone ( gh ) , and tsh led to the hypogonadism ( perhaps , the rcc was causing this pressure effect from the intrauterine period itself and hence resulted in cryptorchidism ) along with hyposomatotropism and hypothyroidism .\nwe also propose that because of its chronic compressive effect with consequent ischemic and pressure necrosis , all cell lineages were affected irreversibly as evidenced by no recovery of pituitary function in the post - surgical reevaluation .\nafter hcg therapy , gonads descended into the scrotum and the patient is on long - term follow - up with replacement of levothyroxine and growth hormone .\nin conclusion , rccs are usually intrasellar or combined intra- and suprasellar , can rarely occur in an entirely suprasellar location with intact diaphragm and intact sella turcica , but a presentation as in our case , with features of hypopituitarism at such a young age , is distinctly uncommon . in the evaluation of cryptorchidism\none should explore the possibility of central causes in the etiology , as this may respond to medical therapy , thereby obviating the need for unnecessary surgical intervention .", "answer": "rathke 's cleft cyst ( rcc ) are benign , epithelium - lined sellar and suprasellar cysts believed to originate from remnants of the rathke pouch . here , we report a rare case of entirely suprasellar rcc in a 4.5-year - old child causing hypopituitarism , who presented to us with bilateral cryptorchidism . subsequently we discuss the distinct rarity of entirely suprasellar rcc presenting in this fashion and the relevant literature is also discussed .", "id": 146} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nceftriaxone sodium is a long acting , broad - spectrum cephalosporin antibiotic for parenteral use .\nit exerts in vitro activity against a wide range of gram - negative and gram - positive microorganisms .\nit is highly stable to most beta - lactamases , both penicillinases and cephalosporinases , of gram - positive and gram - negative bacteria .\na thorough literature survey has revealed that hplc method for ceftriaxone sodium with combination of other drugs and individually in dosage forms [ 215 ] , microbial bioassay methods [ 16 , 17 ] , and spectrophotometric methods in dosage forms [ 1822 ] have been reported for analysis of ceftriaxone sodium .\ncostlier and volatile solvents were used as mobile phase solvent system and the time of analysis was more in some reported methods .\nsome spectrophotometric methods are recently described in the literature for analysis of drugs in raw material and finished products such as ceftazidime [ 2325 ] , cefuroxime , and cefazolin .\nthese spectrophotometric methods involve the use of no toxic organic solvents , which do not contribute to the generation of this kind of waste by the chemicals or industries . in this context\ntherefore , the trend is that the industries look for ways to reduce the impacts of their activities on the environment .\nso , the principle objective of this study was , therefore , to develop a simple , selective , precise , less time consuming , and economical method with a wide linear range and good sensitivity for assay of ceftriaxone sodium in the powder for injection dosage forms .\nthe parent drug stability guidelines issued by the international conference of harmonization ( ich ) require that analytical test procedure should indicate stability .\ntherefore , the present study was extended to establish the inherent stability of ceftriaxone sodium under different stress conditions such as , alkaline , acidic , oxidative , and photolytic conditions .\nthus , this method can be utilized to compare the results for the content analysis of stability samples , since the purpose of stability studies is to monitor possible changes to a product or a material over a time at different storage conditions .\nspectrophotometric analysis was carried out on a systronics 2201 , uv - visible double - beam spectrophotometer with matched 1 cm path - length quartz cells .\nabsorption spectra were recorded on a medium scan speed , setting slit width to be 1 nm .\nceftriaxone sodium was obtained as a gift sample from orchid chemicals and pharmaceutical ltd . ,\nthe other chemicals like sodium hydroxide , hydrochloric acid , and hydrogen peroxide used were of merck - ar grade and double distilled water was used throughout the experiment .\na stock solution was prepared by dissolving 100 mg of ceftriaxone sodium pure drug in 100 ml of distilled water to get standard stock solution ( 1 mg / ml ) . to a set of 10 ml volumetric flasks , aliquot volumes containing the drug were quantitatively transferred from standard stock solution and made up to the mark with distilled water to obtain final concentrations of 550 g / ml of ceftriaxone sodium .\nthe absorbance was measured at 241 nm and calibration graph was constructed by plotting the absorbance versus the concentration of the drug .\nthe validity of the method was tested regarding linearity , specificity , accuracy , and precision according to ich q2b recommendations .\naccuracy and precision of the method were evaluated with the help of percent recovery , standard deviation ( sd ) , and percent relative standard deviation ( rsd ) by using standard addition method .\nthree levels of standard drug ( 10% , 20% , and 30% ) were spiked individually with the 100 mg equivalent of powder for injection dosage form ceftriaxone sodium and analysed in six replicates during the same day ( intraday precision ) and six consecutive days ( interday precision ) .\na linear correlation was found between absorbance at max and various concentrations of ceftriaxone sodium .\nthe linearity graph obeyed beer 's law in the range from 5 to 50 g / ml and it was described by regression equation ( y = mx + c ) and correlation coefficient ( r ) which were displayed on the graph .\nmolar absorptivity , sandell 's sensitivity , standard error on slope , confidence limit of slope ( 95% ) , standard error on intercept , confidence limit of intercept ( 95% ) , lod , and loq were calculated . for the determination of lod and loq ,\nthe method is based on residual standard deviation of regression line and slope . to determine lod and loq ,\nthe specific calibration curve was studied using the sample containing analyte in the range of detection limit and quantitation limit .\nrobustness was studied by evaluating the influence of small but deliberate variations in the experimental condition like storing the similar concentration ( 20 g / ml ) of drug solution at two different temperatures ( 20c and 30c ) for 1 h and performing the stability of the sample solution at various time intervals ( after 1 h and after 6 h ) on the analytical performance .\na 2 ml aliquot of standard stock solution of ceftriaxone sodium ( 1 mg / ml ) was taken in four replicates in a volumetric flask ( 100 ml ) and mixed with 10 ml of 0.1 n hcl ( acid hydrolysis ) or 0.1 n naoh ( alkaline hydrolysis ) or 5% h2o2 ( oxidative degradation ) and set aside for 1 h at room temperature .\na solution of drug ( 20 g / ml ) was prepared as per the procedure under construction of the calibration graph and was exposed to uv radiation of wavelength 254 nm and of 1.4 flux intensity for 24 h in a uv chamber . for thermal degradation solid drug\nwas kept in an oven at 100c for 24 h. after cooling to room temperature , 20 g / ml concentrated drug solution was prepared as per above said method .\nfinally , absorbance of all the solutions resulted from acid and alkaline hydrolysis , and oxidative degradation , photolytic degradation , and thermal degradation were measured at 241 nm against respective solvent as blank in each case .\nfor the estimation ceftriaxone sodium from injection ( by procuring three brands from market ) , a portion of powder equivalent to 100 g of the drug from each brand was accurately weighed and transferred into 100 ml volumetric flask .\nthe drug was dissolved by adding 70 ml of distilled water and sonicated for 15 min .\naliquot containing suitable concentration ( 20 g / ml ) of ceftriaxone sodium was analyzed as described under construction of the calibration graph .\nthe nominal content of the drug in injection for each brand was determined using the corresponding regression equation and results of % rsd of drug content were statistically compared with reported method .\naqueous solution of ceftriaxone sodium showed absorbance maximum ( max ) at 241 nm ( figure 2 ) , and at this wavelength distilled water did not show any significant absorbance .\nleast square regression equation of ceftriaxone sodium in aqueous medium has shown that the r value very close to 1 indicated high degree of correlation between two variables , such as absorbance and concentration ( figure 3 ) .\nbeer 's law was obeyed over the range of 550 g / ml ; high values of molar absorptivity and low values of sandell 's sensitivity and lod revealed that proposed methods are highly sensitive .\nlod and loq values for the drug were found and all the parameters of calibraration curve were displayed in table 1 . to check accuracy and precision ,\nassays were carried out for six times within a day ( intraday precision ) and in six consecutive days ( interday precision ) by adding three different levels of analyte to the formulation .\n% rsd values were 0.5 ( intraday ) and 1.18 ( interday ) indicating high precision of developed method .\naccuracy of the method was ascertained as mean % recovery between measured actual concentration and taken concentration for ceftriaxone sodium .\nthe values of % recovery , very close to 100% , demonstrate high accuracy of the proposed method ( table 2 ) .\nrobustness studies assumed that the small variations in any of the variables did not significantly affect the results ( table 3 ) .\nceftriaxone sodium sterile formulations were analysed by proposed method and by reported method , which involved the analysis of analyte with 0.1 m sodium hydroxide and absorbance measured at 258.8 nm .\nresults were compared by student 's t - test and variance - ratio f - test . calculated t - values and f - values did not exceed tabulated values of 2.776 ( t ) and 6.39 ( f ) at 95% confidence level and for four degrees of freedom ( table 4 ) which indicates close similarity between proposed and reported method .\nceftriaxone sodium was subjected to various stress conditions like acid , alkaline , hydrogen peroxide induced degradation , and thermal and photolytic condition .\nanalysis was performed by measuring absorbance of ceftriaxone sodium after subjecting it to stressed conditions at max of pure drug .\npercentage degradation was calculated by the formula : % degradation = ( expected concentrationactual concentration)/expected concentration 100 , and percentage recovery also was calculated for each case ( table 5 ) .\nresults revealed no change in absorbance of drug solution at alkaline hydrolysis , so its percentage recovery is very close to 100% which indicates the drug stability .\nbut there was significant change in absorbance after acid and hydrogen peroxide treatment , confirming that ceftriaxone sodium is susceptible to acid hydrolysis ( % degradation of 11.0% ) and oxidation ( % degradation of 7.95% ) .\nanalyte undergoes significant degradation under acid hydrolysis and oxidation , whereas it is stable under alkaline treatment .\nproposed method was validated for linearity , accuracy , precision , and robustness and method was applied to various formulations and results were statistically compared with reference method which showed that there were no significant changes in the result .\nso , method can be utilized for determination of purity of drug available from various sources without any tedious procedure and also used in analysis of stability study samples .", "answer": "a simple , selective , and stability indicating spectroscopic method has been selected and validated for the assay of ceftriaxone sodium in the powder for injection dosage forms . \n proposed method is based on the measurement of absorbance of ceftriaxone sodium in aqueous medium at 241 nm . \n the method obeys beer 's law in the range of 550 g / ml with correlation coefficient of 0.9983 . \n apparent molar absorptivity and sandell 's sensitivity were found to be 2.046 103 l mol1 cm1 and 0.02732 g / cm2/0.001 absorbance units . \n this study indicated that ceftriaxone sodium was degraded in acid medium and also underwent oxidative degradation . \n percent relative standard deviation associated with all the validation parameters was less than 2 , showing compliance with acceptance criteria of q2 ( r1 ) , international conference on harmonization ( 2005 ) guidelines . \n then the proposed method was successfully applied to the determination of ceftriaxone sodium in sterile preparation and results were comparable with reported methods .", "id": 147} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nultrasound - guided fine - needle aspiration ( fna ) has become the gold standard for differentiating benign and malignant thyroid nodules due to the suboptimal accuracy using gray scale features alone . besides for mild associated pain ,\ndevelopment of postprocedural hematoma has been reported from 1.9% to 6.4% , with seven reported cases of life - threatening hematomas relating to airway obstruction . the true rate of complications following thyroid nodule fna is likely much higher though as most go undocumented and unpublished .\nalthough fna plays an essential role in thyroid nodule evaluation , the potential for a nondiagnostic ( nd ) specimen can lead to repeat procedures , increasing patient morbidity , cost , chance for complication , and delay in diagnosis .\nrecently , thyroid nodule fna pathological reporting has been standardized based on the bethesda system for reporting thyroid cytopathology adopted by the american society for clinical pathology ( ascp ) . based on their criteria ,\nan adequate specimen needs to contain at least six groups of follicular cells with each group composed of at least 10 cells each .\nan nd specimen can be secondary to obscuring blood , overlying thick smears , air drying of alcohol - fixed smears , or inadequate number of follicular cells . according to the ascp\n, nd specimens occur in 2%20% of cases but ideally should be limited to no more than 10% of all thyroid nodule fnas .\nrecently , the use of ultrasound strain elastography ( use ) has emerged as a promising diagnostic tool in differentiating benign and malignant thyroid . a novel approach aimed at decreasing the rate of nd nodule fna maybe to use elastography as a map , targeting biopsy needles to areas of lower strain ( i.e. , stiffer ) .\nseveral papers have been published illustrating increased detection of prostate cancer using use - targeted interventions through a transrectal approach .\nour study was performed to evaluate the role of use - targeted fna in decreasing the rates of nd aspirates .\nwe performed a review of all thyroid nodule fna performed over a 3-year period comparing fna results when an elastogram was available before fna or not .\nour hypothesis is that the presence of an elastogram before fna would decrease the rate of nd specimens .\nthe study was health insurance portability and accountability compliant , and informed consent was waived .\nbetween january 2011 and january 2014 , a total of 225 patients underwent ultrasound - guided thyroid nodule fna . among them were 171 females and 54 males with ages ranging from 27 to 90 .\nthe demographical data recorded included patients ' age and gender as well as which thyroid lobe contained the nodule biopsied [ table 1 ] .\ngray scale nodule characteristics that were recorded included the presence of microcalcifications , vascularity , solid components , and nodule size [ table 1 ] .\nthe decision to perform use was based strictly on suspicious gray scale characteristics , and guidelines set forth by the society of radiologists in ultrasound .\npatient demographics and nodule characteristics during this period , use for thyroid nodules was performed in cases where the available technician was comfortable and experienced with the elastography software .\nwhen elastography was performed , the applied transducer pressure was standardized by a real - time analysis utilizing a scale that was displayed at the right upper corner of the elastogram image [ figure 1 ] .\nthe nodule strain elastogram was displayed using a 256-color mapping scale [ figure 2 ] .\nthe degree of strain was assigned a given color shade utilizing a range from red ( greatest strain , soft ) to green ( intermediate strain ) to blue ( least strain , hardest component ) .\nreal - time applied transducer pressure analyzed by numeric scale displayed at the right upper corner of the elastogram image ( red box ) .\nnodule strain elastogram is displayed by a 256-color mapping scale with red representing the softest components and blue representing the hardest components .\nwe separated patients into two groups , based if an elastogram was available for the radiologist to review before fna or not .\nall fna were completed by one of two fellowship - trained radiologists with specialty in ultrasound - guided procedures .\na 21-gauge needle was used in every case , and aspiration was aided by a 5-cc syringe .\nall pathological analyses were performed by one of three board - certified cytopathologists . in all cases ,\nthe final pathological diagnosis was reviewed through the institution 's electronic medical record for every case .\nthe chi - square test was used to determine statistically significant variances in the demographic parameters .\nthere was no significant difference between the two groups in demographics ( including gender , age , and which thyroid gland contained the nodule ) as well as nodule characteristics .\nregarding the specimen adequacy , the total percentage of nd aspirates was 12.2% , slightly higher than the 10% supported by the ascp . in analyzing the two groups , when an elastogram was available before fna , the nd rate was 10% ( 14/140 ) which was in concordance with the ascp recommendations\n. however , the group without an elastogram available had an nd rate of 16% ( 13/81 ) .\nhowever , this difference was not found to be statistically significant , p = 0.205 .\nthyroid nodules continue to pose a diagnostic dilemma secondary to poor sensitivity and specificity using gray scale features alone .\nalthough considered the gold standard for nodule evaluation , fna carries its own risks including patient pain , cost , and possible complications ( although rare ) . the need for repeat fna secondary to nd results can cause further patient harm as well as delay time to treatment and increase patient anxiety . to help increase the rate of adequate specimen recovery , the use of ultrasound to guide fna has become the standard of care . with the assistance of ultrasound - guided fna ,\nthe rates of nd specimen aspirates still range up to 20% . in a recent meta - analysis ,\neven the addition of rapid onsite evaluation by a cytopathologist has shown considerable variability in helping to reduce nd rates .\nex vivo studies have found that malignant thyroid lesions have a stiffer architecture compared to benign thyroid stroma .\nfirst described in 1991 by ophir , tissue stiffness could be measured by applying an external axial stimulus and viewing the associated compressibility .\nthe continued research in elastography has focused on its ability to distinguish benign and malignant lesions by virtual palpation .\n several studies have been performed to evaluate the role of elastography in targeting interventions .\nmost papers have focused on ultrasound - guided transrectal biopsies of the prostate gland . using elastograms ,\nsmall studies have been able to show enhanced detection rates as well as decreasing the number of core specimens required for diagnosis . to date\n, there has been only one study performed evaluating strain elastography - guided fna of thyroid nodules . in 2013 ,\nyildrim et al . , prospectively analyzed the rates of nd aspirates between specimens obtained from regions of higher strain and lower strain from 96 patients .\nthe authors found a significant improvement in specimen adequacy when aspirates were obtained from regions that demonstrate a stiff elastogram as described previously .\nour study was aimed at replicating yildrim 's results in a larger patient sample and hoping to show an improved rate of nd aspirates . in our retrospective review , although there was a decreased rate of nd specimens in the group that use was performed ( 16% vs. 10% ) , this was not found to be statistically significant .\nfirst of all , we performed a retrospective review , which by its very nature allows for confounding bias .\nfurthermore , although an elastogram was available for the radiologist before fna in the elastography group , we were unable to prove that stiffer regions were actually targeted and aspirated during the procedure .\nfurthermore , it is possible that stiffer regions of nodules were sampled in the group without elastograms even though elastography was not performed . finally , as our study was a retrospective review , the pathologist performing the specimen analysis was not controlled for , leading to possible variability .\nanother possibility exists to explain why the presence of an elastogram prior the fna did not significantly reduce the rate of nd results .\nour study was predicated on the idea that stiffer regions within nodules would likely decrease nd aspirates as these regions may represent more cellular areas\n. however , the development of a stiff consistency in many cancers is secondary to a desmoplastic transformation that takes place .\nthis process is composed of activated fibroblasts ( also known as myofibroblasts ) , tumor vessels , inflammatory cells , and extracellular matrix components . activated carcinoma induced fibroblasts , along with other extracellular matrix proteins , comprise a dominant proportion of several carcinomas , including more than 90% of overall tumor mass in pancreatic cancers .\nit has even been shown that the complex relationship between these components may promote tumor cell growth .\nit is possible that the stiffer regions within thyroid nodules are more a product of fibroblastic growth than increased cellular density .\nwe were unable to demonstrate a significant difference in thyroid nodule aspirate adequacy between patients who had an elastogram present before fna compared with those without one .\nthese results may be secondary to lack of power , poor study design versus fibroblastic growth as described above .\nwe hope our study raises awareness of the exciting prospect of use - targeted biopsy and springs future studies confirming its potential .", "answer": "objectives : since 2009 , the rate of nondiagnostic ( nd ) thyroid nodule fine - needle aspiration ( fna ) has ranged from 2% to 20% \n . a nd result can cause further patient morbidity secondary to repeated procedures and delay in diagnosis . \n the use of real - time strain elastography ( rte ) in determining nodule malignant risk has gained considerable focus recently . \n a less studied area where rte may prove beneficial is its role in targeting areas for fna . \n our hypothesis is that fna performed in concurrence with rte will show a decreased rate of nd results leading to fewer repeated fna.materials and methods : the institutional review board approval was obtained . \n a retrospective review of all thyroid nodule fna from january 1 , 2011 , to january 1 , 2014 , was performed with review of nodule size , presence of microcalcifications , vascularity , solid components , patient age , and gender . \n cases were separated based if rte was done before fna or not . \n pathology reports were reviewed to assess for specimen adequacy . \n statistical comparison was performed using sas analysis software.results:a total of 221 specimens were reviewed , with rte performed on 140 cases ( 63.4% ) . \n both groups were similar in demographics and previously described nodule characteristics . \n the nd rate when rte was not performed was 16% ( 13/68 ) compared to 10% when rte was performed ( 14/126 ) . \n the difference was not found to be statistically significant , p = 0.205.conclusions:the presence of an elastogram failed to demonstrate a significant decrease in nd fna rates although these results may be secondary to study design . \n further evaluation with prospective trials using larger sample size may ultimately detect increased accuracy of rte - targeted fna .", "id": 148} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncastleman 's disease ( cd ) is a rare lymphoproliferative disorder caused by faulty immune regulation resulting in excessive b - lymphocyte and plasma - cell proliferation in lymphatic tissue .\nmarked interfollicular vascular proliferation leads to mass formation , which can encase bronchi and sometimes cause mural erosion leading to life - threatening hemoptysis .\nvascular supply to these lesions have been reported to arise from the bronchial , internal mammary , and intercostal arteries .\nwe report a case of hilar intrathoracic cd with atypical radiological features where the left inferior phrenic artery and bronchial circulation provided codominant blood supply .\na 24-year - old female with a 5-month history of wheeze and nonproductive cough underwent chest x - ray , which showed a well - defined mass in the left hilar region [ figure 1a d ] . a contrast - enhanced computed tomography ( ct ) scan of the chest revealed a heterogeneously enhancing 7 5 cm mass containing flecks of calcification at the left hilum . 18 fluorodeoxyglucose positron emission tomography ( 18-fdg pet )\nscan demonstrated an inhomogeneous hypermetabolic lesion with no evidence of metastatic uptake . a ct - guided percutaneous core biopsy revealed chronic inflammatory tissue with no evidence of malignancy .\ndue to worsening cough and wheeze , the patient underwent a thoracotomy and surgical resection . during the operation there was massive blood loss of 2000 ml .\nhistopathology confirmed the mass to have marked lymphoid infiltrate with irregular b cell follicles and hyaline vascular - like change consistent with cd .\nchest x - ray of a 24-year - old female ( a ) showing well - defined left hilar mass .\ncontrast - enhanced ct scan ( b and c ) shows heterogeneously enhancing mass with coarse calcifications within this hilar mass .\n18-fdg pet / ct scan ( d ) shows hypermetabolic uptake within the lesion two months after the thoracotomy , the patient presented to the emergency department with a 1-day history of massive hemoptysis ( > 200 ml ) .\na ct pulmonary angiogram for clinically suspected pulmonary embolism showed no pulmonary embolism , however , multiplanar reformats showed low attenuation soft tissue in the surgical resection bed at the left hilum receiving blood supply through hypertrophied left bronchial and left inferior phrenic arteries [ figure 2a f ] .\nthe patient had an embolization through a right common femoral artery approach and the common ( conjoined ) origin of the right broncho - superior intercostal trunk and left bronchial arteries were catheterized with a 5 fr ( cordis , usa ) left amplatz coronary i catheter ( cordis , usa ) .\nthe sharply angulated left bronchial artery could not be superselectively catheterized with a range of microcatheters .\nthe main trunk was embolized with 300500 micron polyvinyl alcohol ( pva ) particles ( cook , usa ) .\nthe medial division of the inferior phrenic artery was seen to supply the mass via its pericardial branch .\nthis was super - selectively catheterized with the same 5 fr catheter and a renegade microcatheter ( boston scientific , usa ) and embolized with the same pva particles .\nno spinal , esophageal , or coronary supply was demonstrated from the bronchial and left inferior phrenic arteries .\nthere were no procedure - related complications and the patient had an uneventful recovery with no further hemoptysis during the 3 years follow - up period .\ncontrast - enhanced ct with mip images ( a and c ) showing blood supply to the lesion with bronchial artery and left inferior phrenic artery ( arrows ) .\ncatheter angiogram demonstrates bronchial artery ( arrow in b ) and left inferior phrenic artery ( arrow in d ) and subsequent embolization with pva ( e and f )\ncd may be localized or multicentric and primarily involves the mediastinum , neck , and mesentery .\nthere are three known histological variates namely ( a ) hyaline - vascular , ( b ) plasma - cell , and ( c ) mixed variant .\nclassic features on a ct scan is a solitary , intensely , and homogeneously enhancing mass with no local invasion .\nthe standard treatment of the localized form is surgical resection , however , where there is encasement or invasion of the adjacent structures , preoperative embolization has been advocated . recently ,\nembolization alone without surgical resection has been shown to terminate hemoptysis and alleviate shortness of breath due to airway compression in patients with unresectable disease . in our patient ,\npreoperative embolization , which may have reduced the large volume intraoperative blood loss , was not considered .\nit was only when the patient presented with hemoptysis after surgical resection that the vascular supply was identified and an emergency referral to interventional radiology was made .\nprevious reports have identified bronchial , internal mammary , and intercostal arteries as feeding vessels to cd .\ninferior phrenic supply to cd has not been reported before to the best of our knowledge .\nwhen basal lung segments are suspected as the source of hemoptysis , inferior phrenic supply should always be considered .\ninferior phrenic supply to hilar masses is much rarer , but when it occurs , the supply is usually via the pericardial branch of its medial division .\nthe left inferior phrenic medial branch may supply the esophagus , and it is important to exclude any esophageal supply before particulate embolization .\ncareful review of multiplanar reformats of the ct scan aided procedure planning and the consent process by identifying the hypertrophied arterial feeders .\ncd should be considered in the differential diagnosis for all benign intrathoracic masses . where a mass shows avid enhancement , whether homogeneous or heterogeneous , a ct angiogram ,", "answer": "castleman 's disease ( cd ) is a rare lympho - proliferative disorder due to faulty immune regulation resulting in proliferation of lymphatic tissue . \n the vascular supply to these lesions have been reported to arise from the bronchial , internal mammary and the intercostal arteries . \n we report a case of hemoptysis secondary to intrathoracic cd with vascular supply arising from the left inferior phrenic artery which was successfully embolised with polyvinyl alcohol ( pva ) particles .", "id": 149} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nattention - deficit / hyperactivity disorder ( adhd ) is a behavioral disorder usually diagnosed during childhood .\nit is characterized by developmentally inappropriate symptoms of inattention , hyperactivity and impulsivity and significant impairment in multiple domains of functioning .\ndiagnostic and statistical manual of mental disorders ( dsm - iv ) diagnostic criteria define three adhd subtypes based on the presence of inattention and hyperactivity / impulsivity symptoms : predominantly inattentive type , predominantly hyperactive / impulsive type , and combined type . a recent us national epidemiological study of 8- to 15-year - old school children found an 8.7% prevalence of adhd , with the predominantly inattentive type most prevalent ( 4.4% ) among the adhd subtypes ( combined type , 2.2% ; predominantly hyperactive - impulsive type , 2.0% ) .\nthe behavioral manifestations of adhd inattentive type differ from those associated with combined and hyperactive / impulsive type .\nchildren with combined and hyperactive / impulsive type exhibit problems with behavioral inhibition , including interrupting , blurting out , getting out of their seat at inappropriate times , and playing loudly .\nin contrast , the primary difficulties of children with inattentive type are non - disruptive in nature and are related to planning and organizing actions .\nchildren with inattentive type often forget to complete or lose assignments , procrastinate , complete work carelessly , have difficulty planning for the completion of long - term projects and studying for tests , and have problems keeping materials organized [ 7 - 9 ] .\nthree treatments qualify as well - established interventions for children with adhd : psychopharmacological therapy , behavioral parent training , and behavioral classroom management .\npsychopharmacological therapy ( e.g. stimulant medication ) is the most utilized intervention modality for treating patients with adhd and produces marked improvements in sustained attention , impulse control and noisy and disruptive behaviors .\nwhile psychopharmacology ameliorates some of the core symptoms of adhd inattentive type , there is minimal evidence to suggest that medication promotes improvements in the ability to effectively plan and organize materials and/or actions . as such\n, stimulant medication is only minimally effective in improving important areas of functioning such as long - term academic achievement .\nsimilarly , evidence - based behavioral treatments , such as parent training and classroom management , primarily target impulsive and disruptive behaviors and do not focus on the problematic behaviors associated with inattentive type .\nin the past 2 years , several advances have been made in the treatment of behaviors exhibited by children with adhd inattentive type .\ninterventions have been evaluated that target planning , materials organization , time - management , and homework management skills .\nthese interventions typically focus on behavior in the school setting as demands for these skills are greatest at school and can lead to significant academic impairment .\nchildren are taught systems for organizing school materials and managing / planning homework responsibilities . checklists with operationalized definitions of behavior are used to monitor skills implementation . similar to existing evidence - based interventions for adhd , these interventions incorporate behavioral therapeutic techniques , such as rehearsal , prompting , shaping and contingency management , to teach and promote skills use and their generalization .\nfor example , point systems or token economies are often utilized to monitor and reward adherence .\ninterventions have been evaluated that target multiple aspects of organization and planning , including : classroom preparation , organization of bookbag , binder , and locker , and planning and tracking homework assignments and long - term projects .\nthese interventions are associated with short - term gains on process measures of materials organization , homework management , planning and procrastination .\nsome of these improvements appear to be sustainable for children with adhd as assessed at 8-week and 3-month follow - ups . at this point , it is unclear if gains on process measures ( e.g. materials organization or homework management checklists ) are ultimately associated with improvement in functional outcomes such as school performance .\nonly a subset of studies completed to date included both process measures and measures of functional impairment .\ndocumented improvements in organizational skills , parent ratings of homework problems , and grade point average . however , the gains in grade point average were relatively small .\npfiffner et al . documented improvements in organizational skills and a clinician completed clinical global impression , and these gains were maintained at a 3- to 5-month follow - up .\nabikoff and gallagher showed improvements in both organizational skills and parent - rated homework problems , but it is unknown if improvements in homework problems resulted in overall academic improvements .\nhence , alternative explanations for observed patient improvements are possible ( e.g. hawthorne effects ) .\nin addition , generalization across settings was not formally assessed in most of the studies .\nit would be important to determine if skills generalize across classrooms or from school to home .\nthe behavioral difficulties of patients with adhd inattentive type may be markedly different from those of children with combined or hyperactive / impulsive type and the targets of treatment will need to be tailored accordingly . while behavioral interventions targeting organization , planning and time - management can not be classified as \na central challenge will be figuring out how to disseminate these interventions into clinical practice .\nthe interventions evaluated to date have varied in where the intervention is delivered ( e.g. school , home , or clinic ) , and dissemination models will need to account for these factors . providing intervention directly in the setting where the skills are most relevant / problematic ( e.g. school ) should allow clinicians to achieve higher levels of skills generalization . to promote dissemination , intervention protocols should be developed that do not require a high degree of clinical specialization to implement and that can be implemented directly in the setting of interest .", "answer": "the behavioral difficulties of children with attention - deficit / hyperactivity disorder ( adhd ) inattentive type differ from those of children with adhd combined or hyperactive / impulsive type . \n existing evidence - based interventions primarily target the disruptive and impulsive behaviors exhibited by children with adhd combined and hyperactive / impulsive type . \n a number of recent advances have been made in the non - pharmacological treatment of behavioral difficulties associated with adhd inattentive type . \n additional research using randomized controlled research designs and long - term follow - up evaluation is necessary before these interventions may be considered established evidence - based interventions for patients with adhd inattentive type .", "id": 150} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrenal transplantation rates are low among patients highly sensitized to human leukocyte antigen ( hla ) because of the high rate of antibody - mediated rejection and subsequent graft loss .\nit was recently reported , however , that preoperative desensitization using an anti - cd 20 antibody ( rituximab ) and intravenous immunoglobulin improved transplantation rates in patients highly sensitized to hla . in contrast , the significance of a positive lymphocytotoxic crossmatch in living donor liver transplantation ( ldlt ) is controversial .\nsuccessful ldlt using a liver graft in which the lymphocytotoxic crossmatch was highly positive is reported .\nthe recipient was a 41-year - old woman with end - stage liver disease due to alcoholic liver cirrhosis ( model for end - stage liver disease score 21 ) . at the age of 20 , she was gravida one , para one .\nshe was considered a candidate for liver transplantation because of repeated episodes of encephalopathy . because of the severe shortage of cadaveric donor grafts in japan , we planned an ldlt , and her husband was willing to donate his partial liver .\nthe abo blood type was identical , but the t lymphocytotoxic crossmatch titer was over 10,000 and the b lymphocytotoxic crossmatch titer was 128 ( complement method with the dilution technique according to the standard national institutes of health technique ) .\nin addition , an examination of anti - hla antibodies using fluorescent microspheres revealed that the recipient had donor specific antibodies ( b51 and b52 ) .\nafter obtaining written informed consent from the patient and donor and the approval of the intra - institutional committee , we proceeded to the preoperative preparations .\nfor preoperative desensitization , the patient was first infused with rituximab 2 weeks before the scheduled surgery ( due to a catheter - associated infection , however , the operation was postponed and ldlt was performed 21 days after initiation of the rituximab therapy ) . as the antibody to hepatitis b core antigen was positive , entecavir ( 0.5 mg / day ) was administered for 3 weeks preoperatively to prevent a possible hepatitis b virus breakthrough .\non postoperative days 1 and 4 , 20 mg of anti - cd25 antibody ( basiliximab ) was administered in addition to the routine methylprednisolone and tacrolimus , as we were anxious about hyperacute rejection . besides , mycophenolate mofetil ( mmf ; 2,000 mg / day ) was started on postoperative day 7 .\nthe postoperative course was uneventful except for an episode of mild acute cellular rejection ( banff score 3 ) on postoperative day 27 , which responded promptly to steroid recycle therapy .\nthe liver biopsy specimen obtained at the time of the acute rejection showed mild infiltration of lymphocytes in the portal area and around the bile ducts .\none year after the ldlt , the lymphocytotoxic crossmatch remained negative and the patient has been well with good graft function.fig . \nacr acute cellular rejection , alt alanine aminotransferase , mmf mycophenolate mofetil , mp methylprednisolone , pe plasma exchange , tb total bilirubin , pod postoperative day the clinical profile of the present patient .\nacr acute cellular rejection , alt alanine aminotransferase , mmf mycophenolate mofetil , mp methylprednisolone , pe plasma exchange , tb total bilirubin , pod postoperative day\nthe impact of a lymphocytotoxic crossmatch - positive liver graft on acute cellular rejection and graft survival remains controversial , both in deceased donor liver transplantation [ 3 , 4 ] and in ldlt [ 57 ] .\nsome institutions have reported significantly unfavorable outcomes in ldlt recipients with a positive lymphocytotoxic crossmatch [ 6 , 7 ] .\nin contrast , our previous results showed that if the titer is low ( no more than 32 ) , a positive lymphocytotoxic crossmatch does not adversely affect the graft or survival in patients without desensitization .\nalthough the significance of a quantitative assessment of the lymphocytotoxic crossmatch has not been reported , the high titer in our present patient led to the need for perioperative desensitization to prevent early graft loss due to antibody - mediated rejection . after considering the results in the present patient ,\nwe have settled the indication criteria for preoperative desensitization therapy at the titer of 1,000 ( t lymphocyte crossmatch ) . in this patient ,\ntherefore , we applied preoperative desensitization using rituximab and plasmapheresis to reduce the high titer of preformed antibodies and b lymphocytes . as a result ,\nthe lymphocytotoxic crossmatch was negative after the 3rd plasmapheresis , and negativity was sustained thereafter .\npreoperative desensitization using rituximab was introduced in abo - incompatible ldlt in 2003 and has dramatically improved the outcomes of abo - incompatible ldlt .\nthe appropriate dosage of rituximab is still controversial , but many previous studies have reported the administration of 375 mg / m of rituximab 13 weeks before the transplant . following these successful cases , we planned the administration of 375 mg / m ( 500 mg / body ) of rituximab 2 weeks before the operation [ 8 , 9 ] .\nsplenectomy is also considered to be effective to reduce antibody production , as the spleen is the site of antibody production .\nafter the operation , the suppression of t - cell function to prevent the initiation of t - cell - mediated antibody production was regarded as indispensable .\nwe have routinely used tacrolimus and steroid as an immunosuppressive regimen , and in this particular patient , we added basiliximab ( postoperative days [ pods ] 1 and 4 ) and mmf .\nmild acute cellular rejection occurred about 3 weeks after the ldlt , but response to the steroid recycle therapy was prompt , and the lymphocytotoxic crossmatch was negative during this episode . in summary , we report a successful ldlt using a lymphocytotoxic crossmatch highly positive graft .\nperioperative desensitization using plasmapheresis and rituximab may provide significant benefits for reducing anti - hla antibodies .", "answer": "we describe a successful living donor liver transplantation ( ldlt ) using a lymphocytotoxic crossmatch highly positive graft . a 41-year - old woman with alcoholic liver cirrhosis was referred as a potential candidate for ldlt , and her husband was willing to donate his partial liver . \n as the t - lymphocytotoxic crossmatch titer was over 10,000 , the patient was first infused with rituximab for preoperative desensitization , and then five rounds of plasmapheresis were performed . after the third plasmapheresis , the lymphocytotoxic crossmatch test was negative . \n a left liver graft including the caudate lobe was implanted , and anti - cd25 antibody ( basiliximab ) was administered on postoperative days 1 and 4 . \n the postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27 . \n although the impact of a lymphocytotoxic crossmatch - positive liver graft on acute cellular rejection and graft survival in ldlt remains controversial , perioperative desensitization may provide benefits when using a highly sensitized liver graft .", "id": 151} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin this issue of critical care , laporta and coworkers review a multidisciplinary working group 's analysis of a case study on the causes of and solutions for staff turnover in an intensive care unit ( icu ) setting .\nthis issue is of profound significance to health care leaders in western countries because the workforce is shrinking as a result of impending baby boomer retirements and , as the population ages , the demand for intensive care services will grow considerably .\nthese demographic factors are further compounded by the fact that the complexity of care provided in the icu demands professionals who are highly trained and skilled . in this environment\n, turnover can be costly to the organization because of the significant expenses associated with recruiting and training workers .\nthere are many well documented reasons for staff turnover in the intensive care setting that are highlighted by laporta and coworkers as core reasons .\nthese core reasons include job dissatisfaction due to inflexible scheduling practises , insufficient opportunity for professional development , as well as a lack of collaborative decision making around clinical and practice issues .\nthe authors discuss that data on icu turnover comes from nursing literature and that this research may be applicable to other health care professionals .\nhowever , it is important not to assume that reasons for turnover are the same among different groups of health care providers and that staff turnover is something to be avoided at all costs .\nfor example , misra - hebert and coworkers state that one contributor to physician turnover is conflict between the physician 's and organization 's philosophy and goals .\nphysician turnover in this case may be beneficial both to the physician and organization if the two parties can not reconcile their differences and the conflict impacts on the ability of both parties to move forward .\nthere are other important reasons for turnover that should be considered by icu leaders , and these include burnout and generational diversity .\nburnout is a prevalent phenomenon in icus , and the nursing literature suggests that issues such as moral distress when engaging in futile care contributes to burnout . in the medical literature causes of physician burnout include volume of work , increased expectations of the public , lack of sleep and the possibility of being sued .\nthe consequence of burnout is that there is a negative impact on quality of care and staff morale , which can ultimately cause turnover .\nfor example , gunderson indicates that physicians who are dissatisfied may engage in inappropriate prescribing patterns .\nneuhauser , furthermore , discusses how environments with rigid systems and attitudes among the leadership will decrease staff morale because staff desire flexible policies and autonomy in decision - making .\nthe generational diversity found in the icu environment can also be a source of turnover of staff .\nit is well documented that generation x ( born in 19651980 ) and the millennial generation ( born in 19802000 ) have a strong desire for more balanced work life than veterans ( born in 19251945 ) and baby boomers ( born in 19461964 ) .\nresearch conducted by lorin and coworkers on internal medicine residents of the millenial generation showed that although 41% considered a fellowship in critical care , only 3.4% chose this training because of lack of leisure time and stress levels among faculty and fellows .\nclearly , it is important for leaders to be attuned to these generational differences when developing recruitment and retention plans and redesigning the workplace environment .\nthe review from laporta and coworkers also highlights the importance of icu leadership working with frontline staff to create a vision and strategy that addresses the core reasons for turnover .\nit is essential that this vision be aligned with the vision , mission and values , and strategic plan of the health care organization .\nfurthermore , the team should assess whether their hospital is highly reputable , has high patient satisfaction , and sufficient resources and equipment to provide care .\nall of these components are signs of a positive work environment , and leadership can build on these attributes to recruit and retain staff . the other key factor in this process is the use of a team work approach\n. team work training in the areas of conflict resolution , learning styles and giving feedback will help the staff to work together to create and achieve an inspiring vision .\nalthough the financial and human resource investments required to engage in this process are considerable , there is substantial evidence in the literature that highly functioning , satisfied teams lead to more efficient patient care and better outcomes .\nstaff turnover is a critical issue that icu leaders need to understand and address in their unit settings .\nattention to this issue with a systematic , evidence - based approach that focuses on team work and collaboration will not only improve retention but will also make the icu a highly competitive and desirable place to work .", "answer": "this commentary discusses laporta and coworkers analysis of a case study on the causes of and solutions for staff turnover in an intensive care setting . \n staff turnover is a significant issue for health care leaders due to the shrinking workforce in western countries and an increased demand for intensive care services as the population ages . \n the commentary considers reasons for turnover such as burnout and generational diversity , and highlights the importance of a team work approach to address the issue of turnover .", "id": 152} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nshallots ( wild garlic / osghordion ) with the scientific name of allium hertifolium , is one of the most famous plants from the alliaceae family . for a long time , shallots have been used as a source of food and medicine in iran .\nthe active ingredients of the plant could be referred to agapentagenin , allicin , omega-3 , omega-6 , and minerals such as potassium , sodium , magnesium , iron , copper , zinc , and manganese .\nthis study was conducted to compare shallots in the traditional and modern medicine in order to make a better use of this precious plant .\nto collect appropriate data , resources and articles in trustworthy databases ( e.g. cochrane library , pubmed , google scholar ) and traditional literature ( e.g. makhzan - ul - adwiah , canon , zakhireh - ye khwarazmshahi ) were studied .\nsubsequently , the findings were reviewed , classified , and reported in a tabular format .\nshallots are rich in fatty acids and minerals with many pharmacological effects such as its effect on the respiratory and nervous system and blood dilution , as reflected in the modern medicine\n. however , certain effects as mentioned in traditional medicine ( e.g. anti - warts , anti - lipoma , anti - kidney stone , and its diuretic effects ) are not covered in research studies of the modern medicine .\ndepending on its natural habitats , shallots have different pharmacological effects for which many usages are mentioned in traditional medicine .\nsome of these effects have been investigated in modern medicine ; however , further evaluation of its safety and dosages for clinical use is necessary .\nfurthermore , some cases have not been studied in modern medicine , which could be the basis for future research .", "answer": "background : shallots ( wild garlic / osghordion ) with the scientific name of allium hertifolium , is one of the most famous plants from the alliaceae family . for a long time , shallots have been used as a source of food and medicine in iran . \n the active ingredients of the plant could be referred to agapentagenin , allicin , omega-3 , omega-6 , and minerals such as potassium , sodium , magnesium , iron , copper , zinc , and manganese . \n this study was conducted to compare shallots in the traditional and modern medicine in order to make a better use of this precious plant.methods:to collect appropriate data , resources and articles in trustworthy databases ( e.g. cochrane library , pubmed , google scholar ) and traditional literature ( e.g. makhzan - ul - adwiah , canon , zakhireh - ye khwarazmshahi ) were studied . \n subsequently , the findings were reviewed , classified , and reported in a tabular format.results:shallots are rich in fatty acids and minerals with many pharmacological effects such as its effect on the respiratory and nervous system and blood dilution , as reflected in the modern medicine . \n however , certain effects as mentioned in traditional medicine ( e.g. anti - warts , anti - lipoma , anti - kidney stone , and its diuretic effects ) are not covered in research studies of the modern medicine.conclusion:depending on its natural habitats , shallots have different pharmacological effects for which many usages are mentioned in traditional medicine . \n some of these effects have been investigated in modern medicine ; however , further evaluation of its safety and dosages for clinical use is necessary . \n furthermore , some cases have not been studied in modern medicine , which could be the basis for future research .", "id": 153} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmy experience in state government has been that after natural or manmade point - source disasters , a governor reflexively turns to the office of emergency management , the department of public safety ( or homeland security ) , or the national guard for advice and counsel .\nthe staffs of these agencies , however , have neither the expertise necessary to guide the response to an epidemic nor an established , ongoing communications and surveillance system with hospitals , laboratories , and medical providers .\nit is essential , therefore , to establish a formal process that allows public health and medical experts to assist elected officials in analyzing and interpreting information about the outbreak and in coordinating the public health response to the outbreak .\nguidance for fiscal year 2002 supplemental funds for public health preparedness and response for bioterrorism issued by the centers for disease control and prevention ( cdc ) requires that a state establish an advisory committee that includes representatives from health departments , first responders , hospitals , and voluntary organizations such as the red cross ( 11 ) . in colorado\nthis advisory committee includes not only the nine groups listed in the cdc announcement but also the presidents of the state board of health , state medical society , and state hospital association ; the state veterinarian ; a wildlife disease specialist ; a medical examiner ; a specialist in posttraumatic stress management ; a pharmacist member of the board of pharmacy ; the attorney general ; the chief public information officer for the state health department ; and , as an ex - officio member , the chief of the colorado national guard ( 3 ) .\nthese persons were named to the committee because they possess useful expertise or connections to the community .\nthe statute authorizing the formation of the committee provided legal immunity to members for their advice ( 4 ) , and the members pledged that they would attend the committee meetings during a bioterrorist attack rather than report to their regular jobs . by meeting regularly\nthe committee members learn about each other s skills , experience , and roles and develop a working relationship that , by itself , can be extremely valuable during a crisis .\none notable absence in the composition of the advisory committee is representation from federal agencies , such as cdc , the federal emergency management agency , the environmental protection agency , and the federal bureau of investigation . although these agencies can not , as a practical matter , attend meetings in every state and large municipality , during a crisis they will have an integral role , and disputes are more likely if the leaders are meeting for the first time in a highly stressful situation .\nfor example , local - state - federal disagreements occurred in the management of the pneumonic plague epidemic in los angeles in 1924 , the last instance of person - to - person transmission of plague in the united states , as well as during the anthrax outbreak in 2001 ( 12,13 ) .\nsome existing state regulations , which in normal times are intended to ensure quality medical care , could hinder community efforts during a bioterrorist attack .\nfor example , consideration should be given to modifying , for a limited period through executive orders , the regulations that control the prescription and dispensing of medicine , licensing of physicians and nurses , and transfer of patients between hospitals .\nproviding antibiotics or vaccinations in mass clinics and obtaining the services of retired or out - of - state physicians and nurses may be necessary .\nin colorado , executive orders that address these concerns have been drafted by the governor s technical advisory committee .\nthe orders would permit a ) health - care providers other than pharmacists and physicians , such as nurses and emergency management technicians , to dispense medications , b ) medicines to be distributed without an identified patient s name on the packet or bottle , c ) practice of medicine and nursing by professionals who are not currently licensed in colorado , provided the practice is restricted to caring for epidemic - associated illnesses and the persons are working under the supervision of a licensed practitioner ( who is given legal immunity for the supervisee s work ) , and d ) persons seeking medical care at one facility to be redirected to another facility without initial assessment or stabilization attempt if the initial hospital is unable to care for any more persons or if a specific facility ( established or temporary ) has been directed to receive epidemic patients , e.g. , those with smallpox .\nthese draft orders must still be tailored to the actual emergency and signed by the governor , but the background legal work can be completed ahead of time . two additional features of the colorado bioterrorism statute exist ; these features were designed to encourage volunteers and remove legal barriers to cooperation among institutions and agencies .\nfirst , the statutory definition of civil defense worker was modified to include a physician , health care provider , public health worker , or emergency medical service provider who is ordered by the governor to provide specific medical or public health services during and related to an emergency epidemic and who complies with this order without pay or other consideration ( 7 ) . with this amendment\n, civil defense workers may receive compensation for injury , including illness caused by bioterrorism , which is suffered as a result of civil defense service .\nsecond , the statute provides that persons and entities [ including hospitals ] that in good faith comply completely with board of health rules regarding the emergency epidemic and executive orders shall be immune from civil or criminal liability for any action taken to comply with the executive order or rule and that the state shall provide compensation for property if the property was commandeered or otherwise used in coping with an emergency epidemic ( 4 ) .\nto ensure that a sufficient number of health - care providers , laboratory technicians , public health epidemiologists , and administrative support workers show up for work during a bioterrorist attack , appropriate personal protection ( e.g. , respiratory protection , vaccination , or chemoprophylaxis ) for the worker and , probably , for household members of the worker are essential . when performing nonstandard work , the worker may also need legal protection , as discussed above .\nplans for a bioterrorist attack should include these factors and be written by the employer who knows how the agency operates and is staffed because people work for an agency , hospital , or institution , not a region .\nnonetheless , coordination of resources should develop mutual aid agreements with neighboring jurisdictions and integrate single institution or agency plans into community , regional , or statewide plans .\nin the 2000 colorado bioterrorism statute , the state board of health was given the new authority to promulgate rules requiring each state and local health department , general or critical access hospital , and managed - care organization to write a plan for responding to bioterrorism ( 7 ) .\nwhile hospitals and health departments may have previously written plans for managing mass casualties resulting from aircraft , bus , or train crashes or natural disasters , such plans need to be modified to include consideration of the special circumstances of bioterrorism ( e.g. , chemoprophylaxis and personal protective equipment for workers , infection control , and handling of laboratory specimens ) .\nbecause pandemic influenza may pose challenges to the medical and public health systems similar to those of bioterrorism , a single plan for both types of epidemics should be drafted .\nduring typical outbreaks of communicable diseases , clear and timely communication by the state health department with multiple local health departments and hospitals can be a challenge . in a bioterrorist attack\n, the communications challenge will likely be greater because many more persons and agencies will be involved .\nthe telephone system may not have sufficient capacity for the increased demand or it may be damaged and disorganized , as happened during the response to the attacks on the world trade centers in new york city in september 2001 ( 14 ) .\nfurthermore , a large , sometimes overwhelming , number of inquiries made by members of the public to the public health agency usually occur during public health crises , and therefore , administrative plans for a bioterrorist event should include consideration of this workload .\nrather than relying on hospital personnel , public health agencies may find it advantageous to station their own personnel with mobile telephone or radio communications equipment in individual hospitals to assure that public health agencies get the information they need as rapidly as possible .\naccomplishing this may require an executive order of the governor that commandeers two - way radios .\nin colorado , board of health regulations require the state and local health departments to include assignment of employees to hospitals in the agency s emergency plan ( 8) .\ndisease reporting requires specification of what to report in what manner and timeframe to which parties .\na first legal step in this process is to require immediate reporting of any suspected or confirmed illness , syndrome , or outbreak caused by any potential bioterrorist agent .\nfor example , colorado regulations were modified in 1999 so that cases of plague , which had been required to be reported within 24 hours of diagnosis by telephone , fax , or through a web - based system , were to be reported immediately only by telephone to an on - call person if the physician or hospital suspected the case was related to a bioterrorist event ( 9 ) .\ndisease surveillance systems are critical not only for the initial detection of an outbreak but also for monitoring the extent and spread of the outbreak and for determining when it is over .\nmanaging a large outbreak would require gathering information from contact tracing and source - of - exposure investigations as well as information about the availability of critical medicine , medical equipment , and the handling of corpses .\nthese information needs are much different than those needed for early detection of an attack .\ntherefore , legal authority for surveillance should be modified as necessary to ensure collection of all information that could be needed by the public health agency to fulfill its duties throughout the epidemic .\nthis legal authority may include requirements for groups that do not commonly report information , such as pharmacists , to provide it .\nadministrative public health orders restricting personal behavior of persons with certain diseases , such as tuberculosis , are relatively common in this country ( 15 ) . such orders are usually hand - delivered to a specific person(s ) , and the restrictions are removed after a specified period , such as after one incubation period or when an ill person is no longer infectious .\nanother type of public health order might involve work restriction , e.g. , health - care providers who can not demonstrate evidence of immunity to a vaccine - preventable disease are not permitted to work during an outbreak of such disease .\nfew , if any states , however , have experience issuing and enforcing large - scale quarantine orders that last more than 12 days . orders restricting large numbers of contacts of cases of plague to home were issued in florence , italy , in 1630 and described in the 1999 book , galileo s daughter ( 16 ) .\nthe enforcement of orders restricting the movement of residents of an entire town in which there was an outbreak of viral hemorrhagic fever was depicted in the 1996 movie , outbreak .\nthe images of severe disease and enforced quarantine are similar in the book and movie and are plausible and disturbing to lay audiences .\na more recent , well - documented example of a large - scale movement restriction was the british epidemic of foot - and - mouth disease of 2001 , which affected many farms and businesses and led to the quarantine and slaughter of 4 million sheep , cattle , and pigs for disease control purposes ( 17 ) .\nin all three examples , a decentralized quarantine was imposed . in general , the advantage of a decentralized strategy ( e.g. , persons are restricted to home ) is that it may reduce the risk for transmission of disease because fewer persons congregate .\nalternatively , the centralized strategy ( e.g. , restricted persons are taken to a sports arena , auditorium , theater , school , or hospital ) is seemingly easier for the government to care for restricted persons and to enforce the order but could allow contagious and noncontagious persons to come into contact with each other .\nanother example of large - scale quarantine occurred in los angeles in 1924 during the last epidemic of pneumonic plague in this country ( 12 ) .\nthree days after the first 15 cases in this outbreak became known to public health officials , eight city blocks that housed approximately 2,500 mexicans were placed in quarantine .\npublic health nurses were sent to the area to make house - to - house inspections to identify new cases , and all patients with suspected cases in the area were examined by physicians at the patient s home and then sent to the county hospital .\nall persons who lived at addresses where cases had occurred were quarantined in the county general hospital , and a spanish - speaking priest and social workers were placed in the area to reassure and calm the residents .\nthe quarantine actions taken in this outbreak were a combination of centralized and decentralized strategies .\nas has been discussed by barbera et al . ( 18 ) , numerous concerns regarding large - scale quarantine exist .\nall states currently have in place varying degrees of legal authority enabling isolation , quarantine , or travel restrictions if needed to maintain the welfare and safety of the public .\ndrafting restrictive orders in advance is less helpful than with the other types of orders discussed above because restrictive orders require more tailoring to the specific circumstances and parameters of an outbreak .\nfactors such as duration and location of restriction are dependent on what the bioterrorist agent is , how it is transmitted , how widely the agent has been disseminated , whether exposed persons can be personally identified , and what resources are available to care for restricted persons .\nnot drafting such orders in advance , however , means that they may be written during the turmoil of multiple agencies trying to control an outbreak .\nauthorities should never hesitate to revise the orders on the basis of on updated information . at the end of the operation topoff exercise , for instance , when the governor had issued a travel restriction order for all of metropolitan denver and cdc\nhad quarantined the entire state of colorado , such orders created many unforeseen problems , including how to enforce the orders , maintain essential community services , and distribute foods and prescription medicines .\naccurate and substantive information given to the public by credible public health and medical experts can do much to allay the fears of the public and encourage their cooperation and participation in constructive , organized community response efforts ( 19,20 ) .\ni have discussed a number of ideas about legal and administrative preparations for a bioterrorist attack , but more work can be done , including development of strategies addressing issues related to mental health , disposal of corpses , performing forensic autopsies , signing death certificates , and managing potential animal vectors of disease .\ni have not discussed the sharing of medical and epidemiologic information between public health agencies and law enforcement agencies , such as the federal bureau of investigation . under normal circumstances , public health officials typically argue that release of disease surveillance information to the criminal justice system will discourage persons with reportable conditions from disclosing to public health officials where they have been and with whom they have had contact . however , a bioterrorist attack is not a routine event , and i recommend that state and local public health agencies review the laws and regulations governing the confidentiality of disease surveillance records and develop a legal and administrative protocol for sharing pertinent and relevant information with law enforcement agencies during a bioterrorist attack ( 21 ) . finally , i have not discussed the protection of civil liberties and due process for persons affected by executive orders of the governor and public health officials .\nthis is an important and difficult issue , especially when well persons are quarantined solely on the basis of their having visited , worked , or resided in a particular location at a particular time , as opposed to having had face - to - face contact with a known contagious person .\npublic health officials and attorneys general should review existing safeguards for the protection of civil liberties and determine whether modifications need to be made for the special circumstances created by a bioterrorist attack .", "answer": "this article proposes and discusses legal and administrative preparations for a bioterrorist attack . to perform the duties expected of public health agencies during a disease outbreak caused by bioterrorism \n , an agency must have a sufficient number of employees and providers at work and a good communications system between staff in the central offices of the public health agency and those in outlying or neighboring agencies and hospitals . \n the article proposes strategies for achieving these objectives as well as for removing legal barriers that discourage agencies , institutions , and persons from working together for the overall good of the community . \n issues related to disease surveillance and special considerations regarding public health restrictive orders are discussed .", "id": 154} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nindian population representing one - sixth of the world population has been the global melting pot of human diversity .\nit has all the world s major linguistic groups and the populations have been shaped by different waves of migrations and admixture ( 1 , 2 ) .\nfurther , stringent mating patterns have led to the existence of several endogamous populations , which makes it an important resource for mapping genes ( 3 ) .\nthe indian genome variation consortium ( igvc ) project , an initiative of the council for scientific and industrial research ( csir)was set up to develop a database of genomic variations in indian population for predictive marker discovery in complex diseases such as diabetes , asthma , neuropsychiatric , infectious and cardiovascular disorders , response to drugs , etc .\nthe phase i of the project was conducted to determine the extent of genetic differentiation in india . toward this genotype data of 405 snps from 75 genes and 4.2 \nmb contiguous chromosome 22 regions were studied in 55 contrasting populations ( 4 , 5 ) .\nthese populations were identified from 4 major linguistic groups namely , austro - asiatic ( aa ) , tibeto - burman ( tb ) , indo - european ( ie ) and dravidian(dr ) spanning 6 geographical regions of habitat ( n , north ; ne , north - east ; w , west ; e , east ; s , south ; c , central ) and different ethnic groups ( lp , large population , caste ; ip , isolated population , tribes ; sp , special population , religious groups ) .\nfive genetically distinct clusters were identified and a set of 24 populations that represent these clusters were selected for the phase ii of the project . in the phase ii , 3824 snps from 834 candidate gene as well as 50 000 ( affy 50 k array ) genome wide neutral markers\nthis initiative lays the foundation for the integration of global genotype - to - phenotype data ( 6 ) with indian population data and development of a federated database .\nto address the need for an online comprehensive resource that enables users to visualize igvc data with integrated information about snps from different resources we have developed igvbrowser as shown in figure 1 . \n\ndistribution of markers in 2.41 mb region in human chromosome 1 from igvc data is displayed along with annotation data from different resources .\ndistribution of markers in 2.41 mb region in human chromosome 1 from igvc data is displayed along with annotation data from different resources .\nthe database includes ( i ) final validated dataset from 1871 samples in phase i comprising of 405 autosomal snps spanning over 75 genes including 90 snps from 5.2 mb region of chromosome 22 from 55 diverse endogamous indian populations ( 3 ) ; ( ii ) phase ii dataset for 3824 snps spanning from 834 genes in 545 samples from 24 igvdb populations and ( iii ) 50 000 ( affy 50k xbai array ) neutral markers in 26 populations .\nthe phase ii populations are a subset of the populations genotyped in the phase i. web - based tool snpper ( http://snpper.chip.org/ ) was used to classify the 4229 markers in phase i and phase ii according to their location in genic regions ( figure 2 ) .\nsimilarly , david ( http://david.abcc.ncifcrf.gov/ ) was used to classify the genes containing these markers according to gene disease association class ( figure 3 ) and their mapping in various kegg pathways ( figure 4 ) .\nwe report that a large fraction of genes are implicated in cardiovascular , metabolic , cancer and immune system - related diseases .\nthus , the igvc data provide a basal level variation data in indian population to study genetic diseases and pharmacology . \n\nmore than 50% of the snps belong to intronic regions and 15% are in coding exons . \n\nfigure 3.bar graph shows the functional annotation of candidate genes in igvc according to gene disease association . \n\nfigure 4.bar graph shows the mapping of candidate genes in significant pathways ( after bonferroni correction ) of kegg pathway database .\nmore than 50% of the snps belong to intronic regions and 15% are in coding exons .\nbar graph shows the mapping of candidate genes in significant pathways ( after bonferroni correction ) of kegg pathway database .\nigvbrowser also included hapmap snp genotype data from phases i + ii and iii of the hapmap project ( http://hapmap.ncbi.nlm.nih.gov/downloads/gbrowse/2009-02_phaseii+iii/gff/ ) based on ncbi b36 assembly , dbsnp b126 from 4 populations : yoruba from ibadan , nigeria ( yri ) ; japanese in tokyo , japan ( jpt ) ; han chinese in beijing , china ( chb ) ; and ceph ( utah residents with ancestry from northern and western europe ) ( ceu ) .\nadditional annotation information including cytogenetic positions , link to pathway annotations in the reactome knowledgebase and mrna sequences were retrieved from hapmap in generic feature finding ( gff ) format .\nannotation data in tab - delimited format for non - coding rna genes and pseudogenes , omim - associated genes , mirbase and snornabase , simple repeats , database of genomic variants were downloaded from ucsc genome annotation database ( http://hgdownload.cse.ucsc.edu/goldenpath/hg18/database ) based on build hg18 . the browser implements one of the widely used platform - independent genome annotation viewer generic genome browser ( gbrowse v1.69 ) , developed by stein et al .\n( 7 ) as a part of the generic model organism system database project ( http://www.gmod.org ) .\ngbrowse is a combination of database and interactive webpage for displaying genomic information along with providing data interoperability across systems running the same software .\nintegrated annotation data from primary sources like ncbi , ucsc and hapmap have been linked with variation data from different ethnic populations in india .\ncompiled data processed into gff format and complete human genome sequence as plain text files were loaded into mysql relational database management system using a script of gbrowse .\na user can query chromosomal region of interest , reference snp i d , hgnc symbols , pathway name or any other unique feature recognized by database as a query .\nit allows researchers to upload their own data in gff format and view it along with data available in igvbrowser .\nin addition , the resource is facilitated with sequence analysis servers maintained by ncbi and ucsc .\nonline data analysis plugins allows text dumps of visible features using a number of standard formats and also facilitates the download of sequence corresponding to selected region .\nthe browser implements one of the widely used platform - independent genome annotation viewer generic genome browser ( gbrowse v1.69 ) , developed by stein et al .\n( 7 ) as a part of the generic model organism system database project ( http://www.gmod.org ) .\ngbrowse is a combination of database and interactive webpage for displaying genomic information along with providing data interoperability across systems running the same software .\nintegrated annotation data from primary sources like ncbi , ucsc and hapmap have been linked with variation data from different ethnic populations in india .\ncompiled data processed into gff format and complete human genome sequence as plain text files were loaded into mysql relational database management system using a script of gbrowse .\na user can query chromosomal region of interest , reference snp i d , hgnc symbols , pathway name or any other unique feature recognized by database as a query .\nit allows researchers to upload their own data in gff format and view it along with data available in igvbrowser\nin addition , the resource is facilitated with sequence analysis servers maintained by ncbi and ucsc .\nonline data analysis plugins allows text dumps of visible features using a number of standard formats and also facilitates the download of sequence corresponding to selected region .\nindian genome variation data would be enormously useful for the dissection of common complex diseases and in pharmacogenomics studies .\nfrequency profiles of markers on disease or drug - related genes that have been generated through the igvc are being used to identify at - risk chromosomes , founders , ld - based mapping , tracing history of diseases in pharmacogenetics as well as reference populations for mapping relatedness ( 3,4,5,819 ) .\nthe interactive web browser , igvbrowser , has been created as a central repository for the current and future dataset on indian populations and is being made accessible in the public domain .\na possible integration of igvbrowser with hgvbaseg2p ( 20 ) can enable researchers for cross study comparison among different populations of the world for disease gene association study .\nindian genome variation project was funded by the council for scientific and industrial research programme cmm0016 and sip0006 .\nfunding for igvbrowser and open access charge is provided by european community 's seventh framework programme ( fp7/2007 - 2013 ) under grant agreement number 200754the gen2phen project .", "answer": "the indian genome variation consortium ( igvc ) project , an initiative of the council for scientific and industrial research , has been the first large - scale comprehensive study of the indian population . \n one of the major aims of the project is to study and catalog the variations in nearly thousand candidate genes related to diseases and drug response for predictive marker discovery , founder identification and also to address questions related to ethnic diversity , migrations , extent and relatedness with other world population . \n the phase i of the project aimed at providing a set of reference populations that would represent the entire genetic spectrum of india in terms of language , ethnicity and geography and phase ii in providing variation data on candidate genes and genome wide neutral markers on these reference set of populations . \n we report here development of the igvbrowser that provides allele and genotype frequency data generated in the igvc project . \n the database harbors 4229 snps from more than 900 candidate genes in contrasting indian populations . \n analysis shows that most of the markers are from genic regions . \n further , a large fraction of genes are implicated in cardiovascular , metabolic , cancer and immune system - related diseases . \n thus , the igvc data provide a basal level variation data in indian population to study genetic diseases and pharmacology . \n additionally , it also houses data on 50 000 ( affy 50 k array ) genome wide neutral markers in these reference populations . \n in igvbrowser one can analyze and compare genomic variations in indian population with those reported in hapmap along with annotation information from various primary data sources.database url : http://igvbrowser.igib.res.in", "id": 155} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncarcinomas producing granulocyte colony - stimulating factor ( g - csf ) are extremely malignant and have a poor prognosis [ 1 , 2 ] .\nthus , a liposarcoma producing g - csf is particularly rare and has only been described in a few case reports [ 1 , 3 ] . here ,\nthe tumor also showed spontaneous rupture , which has not been previously reported for retroperitoneal liposarcoma .\npositron emission tomography using f - fluorodeoxyglucose ( f - fdg - pet ) is used to detect tumors based on elevated glucose metabolism in carcinoma cells .\nit has also been shown that f - fdg uptake by bone marrow is correlated with the peripheral blood neutrophil count , since uptake reflects increased marrow metabolism .\nwe performed f - fdg - pet with computed tomography ( pet / ct ) for imaging of the g - csf - producing tumor and found high f - fdg uptake by the tumor itself and diffuse uptake throughout the bone marrow .\nthese are the first pet / ct images of a g - csf - producing tumor in a urological disease .\nthe patient was a 63-year - old man with a history of hypertension and no specific family history .\nhe was taken to the emergency department of our hospital due to significant aggravation of the pain in late july 2008 . an abdominal ct imaging ( fig .\n1 ) revealed a non - fatty , non - fibrotic , and non - calcified right retroperitoneal tumor of 15 cm in size and retroperitoneal hemorrhage .\nhemorrhagic shock occurred due to spontaneous rupture of the retroperitoneal tumor during the examination , and an emergency transcatheter arterial embolization was conducted .\nthe nutrient vessels were the superior and inferior suprarenal arteries , inferior phrenic artery , renal capsular artery , and the first lumbar artery .\nthree days after admission , the patient was transferred to our department for a more detailed examination of the retroperitoneal tumor .\na routine peripheral hematological examination indicated a high white blood cell ( wbc ) count of 37,820/l and a strong left - shift of the differential leukocyte count , with a neutrophil count of 34,794/l .\nhowever , no infection appeared to be present based on physiological and biochemical findings , and endocrinological tests showed no abnormal findings .\nsince the wbc count remained high after the transfer to our department , further tests were carried out at the department of hematological internal medicine , based on the suspicion of a g - csf - producing tumor or a comorbid hematological disease . in parallel ,\nelevated uptake of < f - fdg correlated with the tumor site ( maximum standardized uptake value , suvmax , was 18.5 ) and the case was diagnosed as malignant .\npet / ct imaging also indicated diffuse uptake throughout the bone marrow , and particularly elevated uptake in the vertebral bone ( suvmax : 10.5 ) ( fig .\n2 ) . however , bone scintigraphy showed no bone metastasis , and bone marrow biopsy revealed little fat , significant hyperplasia , and increased neutrophils , but no findings of metastasis or bone marrow involvement .\nbased on all the above findings and the high serum g - csf level of 2,670 pg / ml ( normal < 8 pg / ml ) , the cause of the increased wbc count was determined to be a g - csf - producing tumor .\na malignant tumor was suspected and right nephrectomy and retroperitoneal tumorectomy were conducted in mid - september .\nhowever , since the tumor had infiltrated into the inferior vena cava , diaphragm and abdominal wall already , only partial resection of the tumor was performed .\nhistopathological tests using hematoxylin - eosin staining showed findings for malignant fibrous histiocytoma mixed with those for well - differentiated liposarcoma ( fig .\nthe tumor was diagnosed as dedifferentiated liposarcoma based on the diagnostic criteria of the world health classification ( who ) [ 5 , 6 ] .\nthe postoperative peripheral wbc count was 21,000/l and the serum g - csf level was 1,170 pg / ml , both of which showed a transient decrease . with informed consent from the patient , only symptomatic therapy , but no chemotherapy or radiotherapy , was carried out while observing the prognosis .\nliposarcomas are morphologically subdivided into five main subgroups : well - differentiated , myxoid , round cell , pleomorphic , and dedifferentiated .\ndedifferentiated liposarcoma was first recognized by evans in 1979 and was defined in 2002 as a tumor with a clear - cut and well - differentiated component clearly separated from or occupying a large area beside a poorly differentiated component [ 5 , 6 ] . among 78 cases of retroperitoneal liposarcoma ,\nfabre - guillevin et al . described 52 cases of dedifferentiated liposarcoma with a differentiated component with features of malignant fibrous histiocytoma ( 36 undifferentiated pleomorphic sarcoma ; 14 fibrosarcoma ; 1 myxofibrosarcoma ; 1 osteosarcoma ; and/or 4 leiomyosarcoma ) , 21 of well - differentiated liposarcoma , 2 of myxoid liposarcoma , 2 of round cell liposarcoma , and 1 of pleomorphic liposarcoma .\nthe cases of dedifferentiated liposarcoma had local recurrence and metastasis at rates of about 40 and 20% , respectively , and a poorer clinical outcome compared to well - differentiated liposarcoma [ 6 , 7 ] .\nthe production of g - csf has been reported in cases of hepatocellular carcinoma , pancreatic cancer , and gastric cancer [ 8 , 9 , 10 ] .\ng - csf - producing carcinomas show aggressive growth and a very poor prognosis [ 8 , 9 , 10 ] .\nthere have only been a few previous case reports of a g - csf - producing liposarcoma [ 1 , 3 ] .\nsix cases of liposarcoma accompanied by leukocytosis have been described in the english literature . however\n, the g - csf level has only been evaluated in 3 cases : in an upper arm dedifferentiated liposarcoma described by sakamoto et al .\n, in a mesenteric pleomorphic liposarcoma reported by nakamura et al . , and in the current case .\nin all 3 cases , the g - csf level and peripheral wbc counts were correlated with the clinical course .\nthe g - csf level and wbc count showed a transient postoperative decrease in our patient , but this was followed by an aggressive clinical course and the wbc count was 145,800/l at the time the patient died .\nno hematological diseases such as leukemia or a leukemoid reaction were observed and bone marrow biopsy only showed hyperplasia .\nthese findings led to the diagnosis of a g - csf - producing retroperitoneal dedifferentiated liposarcoma .\nthis is an extremely rare clinical presentation , with the description of spontaneous rupture of a renal liposarcoma by mazuch et al . \nthe rapid aggressive growth of the g - csf - producing tumor may have caused the rupture , and palliative surgery was performed because of the rupture .\npet / ct is useful for the evaluation of malignant lesions . in cases of carcinoma , diffuse f - fdg uptake in bone marrow is often indicative of bone metastasis or bone marrow involvement . in our case ,\npet / ct showed diffuse f - fdg uptake throughout the bone marrow , which indicated multiple bone metastases .\ndescribed 2 cases of g - csf - producing lung cancer that showed diffuse f - fdg uptake throughout the bone marrow .\ncommented that diffuse elevated f - fdg uptake in bone marrow may be helpful in the diagnosis of a g - csf - producing tumor .\nbone metastasis is a differential diagnosis , and in our case bone scintigraphy and bone marrow biopsy were useful for ruling out bone metastasis .\nmurata et al . showed that f - fdg uptake by bone marrow is strongly correlated with the wbc count ( especially neutrophil count ) and suggested that f - fdg uptake by bone marrow reflects marrow metabolism , which is mainly regulated by granulocyte progenitors and stimulated by endogenous hematopoietic growth factors .\nfound increased f - fdg uptake in patients treated with g - csf and showed that the increased uptake returned to the pretreatment value approximately 1 month after discontinuation of g - csf . the serum g - csf level is likely to be higher in patients with a g - csf - producing tumor than in those treated with g - csf\nthus , for a g - csf - producing tumor , at least 1 month is needed before a pet / ct evaluation after removal of the primary lesion .\nother conditions associated with diffuse f - fdg uptake in the bone marrow include marrow hyperplasia resulting from hemolytic / iron - deficiency / blood - loss anemia .\nin addition , van de weile et al . examined the relationship between bone marrow f - fdg uptake and levels of serum cytokines . in patients with non - small cell lung carcinomas , which are known to produce cytokines , f - fdg uptake by bone marrow\nthus , bone marrow f - fdg uptake in patients with a g - csf - producing tumor may also be related to cytokines such as tgf-. in conclusion , we encountered a rare case of a g - csf - producing retroperitoneal dedifferentiated liposarcoma that underwent spontaneous rupture due to rapid aggressive growth .\nthis case is also the first report of pet / ct imaging of a g - csf - producing tumor in a urological disease .\nin such cases , one needs to be careful to avoid a misdiagnosis of bone metastasis , but imaging may be useful for differential diagnosis of a g - csf - producing tumor in patients with abnormally high wbc counts in the absence of infection .", "answer": "the patient was a 63-year - old man who was referred to our hospital as an emergency case with the chief complaint of abdominal pain . \n an abdominal ct revealed a right retroperitoneal tumor of 15 cm and retroperitoneal bleeding . \n after a transcatheter arterial embolization was performed , the patient was transferred to our department . \n there was no infective focus . \n the white blood cell ( wbc ) count ( 37,820/l , normal range < 8 pg / ml ) and the serum granulocyte colony - stimulating factor ( g - csf ) level ( 2,670 pg / ml , normal range < 8 pg / ml ) were high . \n bone marrow biopsy revealed little fat , significant hyperplasia , and predominantly increased neutrophils , but no findings of bone metastasis or bone marrow involvement . \n a g - csf - producing tumor was diagnosed and right nephrectomy and retroperitoneal tumorectomy were performed . \n however , the tumor had infiltrated into the inferior vena cava , diaphragm and abdominal wall , and only part of the tumor could be removed . in histopathological tests , \n hematoxylin - eosin staining showed malignant fibrous histiocytoma - like findings mixed with those for well - differentiated liposarcoma , and the case was diagnosed as dedifferentiated liposarcoma . \n preoperative 18f - fdg - pet computed tomography showed diffuse 18f - fdg uptake throughout the bone marrow and elevated uptake at the tumor site . \n however , since bone biopsy and bone scintigraphy indicated no bone metastasis or bone marrow involvement , we concluded that pet / ct imaging gave false - positive results in the bone marrow . \n this is the first report of pet / ct imaging of a g - csf - producing tumor in a urological disease . \n the imaging results may be useful for differential diagnosis for this tumor in patients with high wbc counts without infection .", "id": 156} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nachaete - scute homolog 1 basic helix - loop - helix chromodomain helicase dna binding protein 7 central nervous system gamma - aminobutyric acid histone acetyl transferase long interspersed nuclear element 1 neuroepithelial precursor nucleosome remodelling and deacetylase oligodendrocyte precursor cell silencing mediator for retinoid and thyroid receptors nuclear receptor corepressors\na look into the pubmed database reveals that sox2 is one of the most studied transcription factors of recent years . in 2013 alone , there are about 750 publications mentioning sox2 in title or abstract .\nafter all , sox2 is intimately linked in the scientific consciousness to stem cells , both embryonic and neural , where it is key to induction and maintenance of pluripotency .\nit is also one of the 4 classical reprogramming factors that are necessary for the generation of induced pluripotent stem cells .\nsox2 is originally expressed in all blastomeres , and later in all cells of the inner cell mass and the epiblast .\nhigh sox2 expression results both in the suppression of mesendodermal differentiation , and the induction of a neuroectodermal fate . in the early neuroectoderm\n, sox2 is expressed in all nep ( neuroepithelial precursor ) cells often together with its close relatives sox1 and sox3 .\nthese 3 related proteins constitute the soxb1 group , and jointly ensure expansion and maintenance of nep cells .\nexpression of sox2 remains associated with nep cells throughout development of the early neuroectoderm into the cns ( central nervous system ) , and is even maintained in the adult where sox2 is found in adult neural stem cells in the subventricular zone of the lateral ventricle walls and in the subgranular zone of the dentate gyrus .\n. one of the mechanisms by which this is achieved , is suppression of premature neurogenesis . in accord ,\nsoxb1 proteins have been shown to counteract the activity of proneural bhlh ( basic helix - loop - helix ) proteins such as ascl1 and ngn1 in the early neural tube , and to repress neuronal gene expression . at first glance soxb1 proteins therefore appear to function prominently as repressors .\nindeed , such functions have been described for sox2 in studies on the transcriptional regulation of the neurod1 transcription factor and line-1 retrotransposons which both exert neurogenic activity .\nit has been postulated that sox2 represses neurod1 and line-1 expression by direct binding to the corresponding regulatory regions and recruitment of transcriptional co - repressors such as hdac1 ( histone deacetylase1 ) so that wnt/-catenin - dependent activation of transcription can not take place . while such function as a classical transcriptional repressor exists for a subset of its target genes and is thus biologically relevant , there is ample evidence that soxb1 proteins when acting as transcription factors \nthis is already suggested by standard in vitro tests for transcriptional activity , which readily identify a transactivation domain in the proteins carboxyterminal half , but fail to detect repressor functions .\nresults from in ovo electroporation experiments in the early chicken neural tube also point to a predominantly transactivating function . in this type of experiment ,\nsox2 function is mimicked by a chimeric protein in which the aminoterminal half of sox2 ( which includes its dna - binding hmg - domain ) is combined with a constitutively active heterologous transactivation domain from the herpesviral vp16 protein .\nanalogous combination of the aminoterminal half of sox2 with the strong repressor domain of the drosophila engrailed protein in contrast changed properties completely and reversed sox2 from an anti - neurogenic into a neurogenic factor as the resulting chimeric protein forced nep cell cycle exit and induced premature expression of neuronal markers .\nthis argues that suppression of neurogenesis is mostly indirect and involves the induction of factors , that then act as inhibitors of neurogenic proteins . what these factors are has not yet been analyzed in detail . \n\nsox2 exerts its diverse effects on gene expression during cns development by influencing epigenetics , transcription and micrornas .\nit regulates histone modifying enzymes and chromatin remodellers as a pre - patterning factor , and at the same time acts as an activating ( or repressing ) transcription factor to influence transcription of pluripotency and differentiation genes .\nadditionally , it impacts on neural and glial gene expression through modulation of micrornas . \n \nsox2 exerts its diverse effects on gene expression during cns development by influencing epigenetics , transcription and micrornas .\nit regulates histone modifying enzymes and chromatin remodellers as a pre - patterning factor , and at the same time acts as an activating ( or repressing ) transcription factor to influence transcription of pluripotency and differentiation genes .\nin addition to its role as transcription factor , sox2 has epigenetic , chromatin - associated functions ( fig .\ngenome - wide chromatin immunoprecipitation studies suggest that sox2 functions as a pre - patterning or pioneer factor ( for review see ref .\nsuch factors have the capacity to preselect and bind regulatory regions and thereby configure the local chromatin in a way that the corresponding genes are kept in a poised state . as such\nthey are not yet actively transcribed , but have the potential to be easily activated in ensuing developmental stages , provided certain preconditions are met . in the context of neurogenesis , this means that sox2 not only binds to regulatory regions of genes whose products are required for realization and maintenance of nep cell properties .\nit is also bound to regulatory regions of many neuronal differentiation genes , and thereby ensures that these genes can later be activated . for this to happen\n, sox2 is down - regulated and replaced on these regulatory regions by other factors , in particular the soxc proteins sox4 and sox11 , which then cooperate with proneural and other neurogenic factors to drive neurogenesis .\nthis role as pioneer factor is supported by results from recent proteomic analyses , that find sox2 associated with many different histone modifying and chromatin remodelling complexes and proteins including nurd , smrt / ncor , swi / snf , chd7 , hats and hdacs .\nthis aspect of the overall function of sox2 is equally important as its classical transcription factor function .\nalthough impossible to separate , one might argue in a somewhat simplistic manner that the role as transcription factor is most obvious for maintenance of nep cells and suppression of premature neuronal differentiation , whereas its role as pre - patterning / pioneer factor defines developmental potential and thus guarantees pluripotency . during development ,\noligodendroglia develop through the opc ( oligodendrocyte precursor cell ) stage into mature oligodendrocytes , the myelinating glia of the cns .\nwe noted that expression of sox2 and sox3 is maintained after nep cell specification into opc , and is downregulated in the oligodendroglial lineage not earlier than during terminal differentiation to mature myelinating oligodendrocytes .\nby analogy to neuronal development we initially assumed that soxb1 proteins would ensure opc maintenance and suppress differentiation into oligodendrocytes .\nneither deletion of sox2 alone nor in combination with sox3 interfered with proper proliferation or generation of opc in normal numbers .\nthus , the role of sox2 and the related sox3 during oligodendrogenesis differs dramatically from the one during neurogenesis with soxb1 proteins being involved in oligodendroglial differentiation events rather than the maintenance of progenitor characteristics . despite this clear - cut overall difference\n, it should be noted that differentiation functions have also been detected or proposed in late developmental phases of certain subtypes of retinal or gabaergic telencephalic neurons .\nthis argues that it is not a complete black - and - white between neurons and glia .\nour mechanistic studies indicated that sox2 is bound to regulatory elements of myelin genes and that soxb1 proteins can act as moderate transactivators of glial differentiation genes ( fig .\nhowever , activation potential appears much less than that of other activators of myelin gene expression such as sox10 and olig2 .\nconsidering that expression of the latter is essentially unaltered in the combined absence of sox2 and sox3 , it appears unlikely that the differentiation defect observed in soxb1-deficient oligodendroglia is attributable to the lack of direct activation of differentiation genes by sox2 and sox3 .\nrather we found evidence for an alternative mode of action that involved a microrna ( fig .\n, sox2 counteracts expression of mir145 , which targets pro - differentiation factors such as the transcription factor myrf ( myelin gene regulatory factor ) or the mediator subunit med-12 that is equally required for terminal differentiation of oligodendrocytes . in the absence of sox2 , terminal differentiation of oligodendrocytes and hence myelination\nare reduced at least in part because mir145 is de - repressed and inhibits expression of myrf and other factors that favor myelination .\nour studies thus identify sox2-dependent modulation of microrna expression as another important facet of its action .\nintriguingly , we also found evidence for a repressive influence of mir145 on sox2 expression , similar to what has been described in glioblastoma cells .\nthese findings argue that a reciprocal negative feedback - loop may exist in developing oligodendroglia between the 2 regulators .\nthe overall impression from current studies therefore is that in addition to its role as a transcriptional activator \nsox2 primarily functions as a pre - patterning / pioneer factor during neurogenesis and as a microrna regulator during oligodendrogenesis ( fig .\nthus , it is legitimate to ask whether sox2 function during the 2 processes is indeed mechanistically as different as the evoked effect .\nalthough there is no definite answer to this question , we like to suggest that this is not the case .\nwe rather assume that sox2 relies on all its different modes of action in both processes .\nas already mentioned , we have found sox2 on regulatory regions of myelin genes in our study .\nwhile this is compatible with a role of sox2 as a weak activator of myelin gene expression , it could equally be interpreted as the result of a pre - patterning function in which sox2 preselects those regulatory regions in opc that have to be activated later on in differentiating oligodendrocytes following the exchange of sox2 on these regions by sox10 .\nthus , it seems perfectly plausible that sox2 also functions as a pre - patterning / pioneer factor in oligodendroglial differentiation . on the other side , a first functional link between sox2 and a microrna was recently detected during in vitro neurogenesis .\nsox2 was found to activate expression of lin28 , which is a potent inhibitor of expression of the let-7 microrna family . let-7i in turn inhibits neuronal differentiation , by targeting among others the 2 proneural genes ascl1 and ngn1 .\nthese findings provide support for the assumption that at least some of the long known repressive effects of sox2 in nep cells on neurogenesis may be mediated by micrornas that are under direct or indirect control of sox2 . in our opinion , sox2 is a true central regulator of gene expression because it acts not only at the transcriptional level , but also pretranscriptionally as a chromatin - associated pioneer factor and posttranscriptionally as a microrna modulator .\nits mechanistic versatility is not only basis for its central role in many regulatory networks , but also endows it with a tremendous flexibility that allows it to acquire different tasks in diverse developmental setups including maintenance of the precursor state , suppression of neurogenesis and promotion of glial differentiation .", "answer": "the transcription factor sox2 is best known as a pluripotency factor in stem and precursor cells and its expression generally correlates with an undifferentiated state . \n proposed modes of action include those as classical transcription factor and pre - patterning factor with influence on histone modifications and chromatin structure . \n recently , we provided the first detailed analysis of sox2 expression and function during development of oligodendrocytes , the myelin - forming cells of the cns . \n surprisingly , we found evidence for a role of sox2 as differentiation factor and found it to act through modulation of microrna levels . \n thus , we add new facets to the functional repertoire of sox2 and throw light on the networking activity of this multitasking developmental regulator .", "id": 157} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe gene expression pathway initiates at nuclear transcription generating a pre - mrna , which very often undergoes splicing , post - transcriptional regulation , and then translation into a protein . during the pre - mrna splicing process\n, introns are removed and exons are joined in order to generate the mature mrna [ 13 ] .\nthe formation of this functional megacomplex is an orchestrated assembly of proteins and rna that requires identification of exon - intron boundaries .\nexons are regularly alternatively spliced , meaning that they are either included or excluded from the final mature mrna transcript .\na recent comprehensive sequencing study observed that more than 90% of the genes undergo alternative splicing .\nthis vastly increases the transcriptome repertoire , and emphasizes both the significance of splicing and the requirement for its accurate execution .\nin addition to protein coding genes , noncoding genes are transcribed . micrornas ( mirna ) , the most comprehensive noncoding group , are a class of ~22 nt noncoding rnas that inhibit gene expression through binding to the 3 untranslated region ( utr ) of target mrna transcripts [ 6 , 7 ] .\nthere are hundreds of unique mirnas in a given species , each predicted to regulate a plethora of target genes [ 913 ] .\nin fact , computational predictions indicate that mirnas may regulate 60% of all human protein coding genes .\ntherefore , it came as no surprise that mirnas were linked to many cellular processes such as differentiation , growth , and apoptosis , while mirna perturbations were associated with numerous diseases , including cancer [ 16 , 17 ] . in the past few years\n, the pivotal role played by mirnas in gene regulation has been recognized [ 1820 ] .\nmirnas are processed through a series of post - transcriptional biogenesis steps . the canonical maturation pathway , similar to protein - coding genes , initiates at transcription ( mostly by rna polymerase ii ) generating a primary ( pri- ) mirna .\nthe pri - mirna is characterized by a hairpin rna structure recognized by the nuclear rnase - iii enzyme drosha , and its cofactor dgcr8 .\nthe microprocessor cleaves the pri - mirna to generate a shorter hairpin of about 70 nt length the pre - mirna .\nthis intermediate mirna is exported from the nucleus to the cytoplasm via exportin-5 where the rnase iii endonuclease dicer generates the final mature mirna .\nthis short rna loses one of its strands ( the complementary mirna * strand ) while the other is loaded onto an argonaute - containing rna - induced silencing complex ( risc ) which mediates gene silencing .\nonce the mirna binds to its target gene , regulation takes place mainly through mrna degradation or translation inhibition [ 22 , 23 ] ( see figure 1 ) . for simplicity , the widely used term\nmirnas can be located inter- or intragenically . when intergenic , their expression is coordinated with other mirnas as a cluster [ 25 , 26 ] .\nwhen intragenic , namely , positioned within a protein - coding gene ( almost exclusively in introns ) , they are often expressed from the same strand as their host - gene [ 2730 ] and at correlated levels . given that both coding mrnas and mirnas are generated from the same transcriptional unit , and that they cooccur in close cellular proximity , it would be puzzling if these events exhibited total independence .\nrecent studies , from transcription , mirna - processing , and splicing oriented perspectives , have investigated these fascinating interactions and yielded interesting , yet somewhat controversial findings .\nrelationships between intronic mirnas and the processing events of their host mrna , namely , transcription and splicing have been addressed . here\nwe outline the major studies in the field . expressed sequence tag ( est ) libraries of expressed mrnas\nthe ests represent a snapshot of cellular transcripts at a particular time point and thus display the given mrna plethora and its variety at a particular cellular state .\nanalysis of this data revealed several chimeric transcripts containing mirna and part of the adjacent mrna sequences . at an early stage of mirna research\nnotably , at a later stage , some of these est fragments were shown to be partially spliced , with either 5 or 3 ends matching putative drosha cleavage sites .\nthese results strengthened the possibility that mirnas and mrnas are processed from the same rna substrate .\nin addition , the correlated expression pattern of host - gene transcripts and their mirnas suggested that mirnas have coevolved to use the same promoter for transcription .\nalong with this work , by comparing mirna processing in a construct containing only the intronic sequence versus one that also includes the flanking exons , pawlicki and steitz found that the levels of pri - mirna transcribed from introns are increased in the presence of flanking exons , due to prolonged retention at the site of transcription .\nthis supported the notion that flanking exons may facilitate mirna processing by increasing the time pri - mirnas spend tethered to the dna template [ 33 , 34 ] .\naltogether , the data indicates that intronic mirna processing is enhanced by physical proximity to the site of transcription , and possibly also by splicing of the host gene .\nseveral groups have isolated and identified various proteins associated with the human microprocessor complex [ 3537 ] . in these studies ,\nnumerous microprocessor - associated proteins were identified as splicing factors ( e.g. , hnrnph1 ; ) or involved in pre - mrna processing ( e.g. , dhx15 ; ) . taken together , based on mirna - mrna transcriptional ( est ) evidence ; shared promoters ; facilitated biogenesis when flanked by exons ; and overlapping proteins between the functional complexes , the data suggests that the microprocessor is potentially enhanced and present during transcription and most likely also during splicing .\nif the same rna substrate is subjected to both host - gene and intronic mirna maturation , the intriguing question raised is how do all these processes transcription , pre - mrna splicing , and mirna processing \nthe complexity of the mirna - host - gene interaction model has increased recently when studies from the proudfoot laboratory demonstrated that pre - mirnas are generated through cotranscriptional cleavage by drosha .\nsuggested that efficient clearance of intronic sequences following microprocessor ( drosha ) cleavage may act to enhance the splicing efficiency .\nthese researchers showed that the microprocessor complex , as well as 5-3 and 3-5 rna exonucleases , are recruited to chromatin associated with intronic mirnas during transcription of the host primary transcript , and that drosha cleavage occurs before host intron splicing .\nthey found that mirna - harboring transcripts preferentially associated with chromatin fractions , from which they concluded that both pre - mirna cleavage and intronic splicing must occur on the same nascent transcripts .\nthe rapid exonucleolytic removal of intronic sequences may clear the proximal vicinity of rna processing for the purpose of efficiently completing the pre - mrna splicing task .\nthe enhancement of splicing by the microprocessor does not agree with other studies [ 30 , 40 ] ( discussed below ) and does not concur with experiments in yeast that showed enhanced processing for sirna flanked exons in splicing mutants .\ndependencies are seen , for example , during the biogenesis process of small nucleolar rna ( snorna ) [ 4244 ] . in the process of snorna maturation , functional links between intronic snornp assembly ,\nan antithesis to this dependency is the alternative mirna biogenesis pathway that bypasses the microprocessor via generation of mirtrons [ 48 , 49 ] .\nthis mechanistically distinct class of intronic mirnas stem from very short introns where splicing substitutes the first step of mirna biogenesis . in this case , splicing activities replace the requirements for a microprocessor . however , not all roads lead to the observed dependency between microprocessing and splicing .\nying and lin have designed an artificial intron containing a pre - mirna secondary structure .\nthey used this construct to show that the mature mirna was released only from the spliced intron .\nthis suggested that spliced introns are subsequently used by drosha and argued against any physical link between the microprocessor and the transcriptional unit or between the microprocessor and the spliceosome .\n. showed that exons of pre - mrna are tethered to the elongating rna polymerase ii either directly or indirectly without affecting processing , indicating that cotranscriptional cleavage of nascent intronic mirna transcripts does not affect splicing efficiency [ 40 , 51 ] . supporting the same view , kim and kim addressed mirna biogenesis in light of the splicing mechanism .\nthey demonstrated that cleavage of an intronic mirna did not significantly affect the production of mature mrna and , conversely , the production of mature mirna was not significantly affected by splicing . in their experiments ,\nknockdown of drosha , or mutations in the mirna hairpin , eliminated mirna generation without dramatically affecting mrna splicing .\nthis suggested that mirna biogenesis and splicing are coordinated but not functionally linked or interdependent . taking a closer look\n, however , they also mention that drosha knockdown led to a modest increase in spliced mrna production and so did mutations in the mirna hairpin .\ntheir work showed that the adjacent introns were spliced more rapidly than mirna - encoding introns , suggesting that binding of the microprocessor may eventually interfere with the splicing to some extent .\ntaken together , kim and kim 's data imply mostly independent activities but can not exclude the possibility that the microprocessor interferes , to some level , with splicing . attempting to explain how both mirna and mrna are generated from the same dna locus , reconciling with the studies described here , we come up with two distinct models .\nthe second predicts generation of an mirna and mrna products arising from two independent rna transcripts ( see figure 2 ) . if the latter scenario was true , microprocessing and splicing would be independent of each other\n. the outcome would be either no functional hindrance between the microprocessor and spliceosome activities or a competition for available pre - mrna substrates .\nin the event that both rna products originate from the same precursor , it is conceivable that the two processes happen consecutively .\nthis would imply that execution of one process would be a prerequisite for the other to occur .\nalternatively , mirna processing and mrna splicing may be coordinated so that the microprocessor and spliceosome interact with each other .\nthis interaction may be minimal , without affecting the amounts of mirna and mrna produced as was suggested recently , or it may constitute a level of regulation .\nwe note that these events should always be looked at in the spatial - temporal context meaning that the microprocessor might act at an independent rate prior to the spliceosome assembly , and thus their direct interaction would be prevented . due to accumulating evidence , both in favor and against dependencies between splicing and microprocessing ,\nthe potential coordinated activity between the microprocessor and the spliceosome can be stratified into four possible relationships .\nthe microprocessor can inhibit or activate the spliceosome , and the spliceosome can inhibit or activate the microprocessor ( figure 3 ) .\n, the microprocessor could activate the spliceosome by recruiting splicing factors to intronic mirnas , while at the same time the spliceosome could inhibit microprocessing .\nwe can not rule out , however , that these relationships occur in one large complex depending on the presence of particular rna processing proteins within the microprocessor .\nmany complex regulatory loops , both positive and negative , were seen in other cellular systems ( e.g. , see [ 52 , 53 ] ) .\nthe microprocessor , on the other hand , is composed of a handful of proteins [ 21 , 36 ] , minimally described as a two - protein complex [ 24 , 35 ] ( alternatively , see ) .\nit is hard to visualize these two very differently - sized complexes aligned at the same position , competing for the same substrate .\nthus , a coordinated processing and crosstalk seems necessary for these complexes the microprocessor and the spliceosome to be able to process the same transcript with intricate accuracy . during the mrna splicing process\n, the rate at which transcription takes place may affect the transcripts ' pattern of splicing .\nthus , kinetics of intron removal and exon ligation may play a role in selecting particular spliced isoforms .\ngiven that some introns undergo mirna excision , unless the removal is extremely rapid , one can imagine a possible effect on splicing outcome .\nthus , from an evolutionary perspective , an intronic mirna might evolve to participate in determining splicing kinetics .\nconsequently , an evolutionary driving force may direct mirna positioning within the intron to prevent disruption of relevant splice signals ( also see ) . in summary\nhow widespread is the mechanism and does it govern all intronic mirnas ? to date , not all microprocessor and spliceosome crosstalk scenarios ( as described in figure 3 ) have been identified . yet , given the complexity of cellular pathways , it is probably only a matter of time before their elucidation .", "answer": "micrornas ( mirnas ) are often hosted in introns of protein - coding genes . given that the same transcriptional unit can potentially give rise to both mirna and mrna transcripts \n raises the intriguing question of the level of interaction between these processes . \n recent studies from transcription , pre - mrna splicing , and mirna - processing perspectives have investigated these relationships and yielded interesting , yet somewhat controversial findings . here \n we discuss major studies in the field .", "id": 158} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nMOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH\n\nPaper sections:\n\nHowever, information about intermediary reservoir is still unknown [1]. Coronaviruses (CoVs) are the enveloped positive stranded RNA viruses, supposed to be possessing largest viral RNA genome known till date [2,3]. As per the recent situational report released by World Health Organization (WHO) on March 28, 2020, 571678 COVID-19 cases have been confirmed globally, including 62514 new cases and total 26494 deaths [4]. SARS-CoV-2 a highly infectious and pathogenic coronavirus has become global concern [5].
Recently sequence analysis confirmed that the SARS-CoV-2 belongs to the class of \u03b2-coronaviruses including SARS-CoV and MERS-CoV. [6)]. Since, SARS-CoV-2 is novel pathogenic coronavirus, till date no effective antiviral therapy is available. Preventive and supportive therapies are main approach for management of COVID-19. Around the globe researchers are endeavoring for the development of effective prevention and treatment strategies for COVID-19. Preliminary studies have suggested potential repurposing of available anti-viral drugs like protease inhibitors lopinavir/ritonavir, nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (arbidol), tenofovir disoproxil (TDF), and lamivudine (3TC), etc. for the treatment of COVID-19 infected patients [7]. In another study Camostat mesylate, a clinically approved TMPRSS2 inhibitor was found to block SARS-CoV-2 entry to human cells, indicating its therapeutic potential as a drug against COVID-19 [8]. Xu et al. (2020) in another investigation screened 1903 approved drugs by homology modeling, molecular docking and binding free energy calculation and suggested nelfinavir as potential inhibitor against SARS CoV-2 [9].
A sizeable body of data demonstrates anti-coronaviral effect from several natural products and herbal medicines. In separate investigations Phenolic compounds of Isatisindigotica, Amentoflavone isolated from Torreya nucifera and Houttuyniacordata water extract have shown SARS-CoV 3CL protease enzyme inhibitory potential against SARS-CoV. (10)(11)(12) Since the Main Protease M pro or Chemotrypsin-like-protease (3CL) which is highly conservable among SARS CoV and SARS-CoV-2 proved by sequential analysis; is suggested to be potential target to fight SARS-CoV-2 [6]. Recently, Khaerunnisa et al, reported M pro Inhibitory potential of kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate against COVID-19 [13]. Prompted by this, in present study we investigated Caffeine, Capsaicin, Hypericin, Gossypol, Luteolin, Berberine, Embelin,Oxyacanthine, Sanguinarine and Emodin as potential inhibitor candidates for SARS-CoV-2 M pro with the help of molecular docking study.
\n\nMaterial and Methods\nThe crystal structure of the molecular target, protease enzyme (COVID-19 3cl pro /M pro (PDB ID: 6LU7), was retrieved from RCSB protein data bank (https://www.rcsb.org/) [14]. Target needs to be prepared before starting the molecular docking process, which involves removal of the water molecules and native ligand attached with target and other heteroatoms which may provide hindrance in the simulation. Besides, hydrogen atoms were added into target. These all processes were carried out in the Auto Dock window execution file. Investigational ligands were designed using ChemSketch (ACD 2012) and optimized for energy minimization using MM2 force field and saved in.mol format subsequently converted into .pdb format by Open Bable -2.3.2 software. The investigation ligand was loaded and their torsion salong with rotatable bonds are assigned and the files are saved as ligand. PDBQT. In the current study, identification of binding modes of the herbal molecules with targetwas identified using Auto Dock 4.2 software program. Moreover, to confirm actual binding interaction with targets blind docking was performed and the best conformers were represented with lowest binding energy (-kcal/mol) which might pave the way to disclose the mode of actions of these ligands. The docking parameters were defined as coordinates of the center of binding site with x = 126, y = 126, z = 126 and binding radius = 0.375 \u00c5. All AutoDock output file (.dlg) were then analyzed through Analysis option provided in MGLTools-1.5.6 rc3. Top-scoring molecules in the largest cluster were analyzed.
Conformers of the ligand were automatically docked to the enzymes and most stable conformer in terms of binding affinity (most negative) was used for post-docking analysis.
\n\nResults and Discussion\nTable1 shows the ligands structures and necessary hydrogen bond formation by ligands with targets required for inhibition of target enzyme of covid-19. The rationale of choosing these ligands is only that they have shown efficacy in preclinical experimental models in different diseases. The SARS coronavirus main peptidase (SARS-CoVMpro) plays an essential role in the life cycle of the virus and is a primary target for the development of effective antiviral agents in case of COVID-19 infection. Figure 1 indicates the active site of target to confirm the binding site of investigational ligands if they were interacted with the amino acids in the active site of target or found to be attached any other site inside the target. The active site of this target enzyme comprises The active site of this target enzyme is composed of HIS41, MET 49, PHE140, LUE141, ASN142, GLY143, HIS163, HIS164, MET165, GLU166, LEU167, PRO168, HIS172, GLN189, THR190, ALA191 (Figure 1).
The best poses of natural ligands and enzyme complexes are described, and the number of hydrogen bonds formed by both proteins with the drug are displayed in figure 2(a-j) as well as in the table1.
Figure1: Active site of target enzyme. GLY143, HIS163, HIS164, GLU166, GLU189 and THR190. In the current study, molecular docking analysis reveals that although all-natural ligands interacted in the active site of target enzyme but some of them could not interact through hydrogen bonds with target which are required for enzyme inhibition.Caffeine is a CNS stimulant, exhibited least binding affinity (-4.520 kcal/mol) towards enzyme but could afford to form required some hydrogen bonds with GLY143 and HIS163 amino acids residues of enzyme. Berberine is an alkaloid, showed slightly good binding energy (-7.910 kcal/mol) than that of Caffeine but could interact with enzyme through different amino acid viz. ASP187 and produced different conformational changes in the target enzyme after binding than that of caffeine (see figure2 b and 3b).
Although Luteolin exhibited moderate binding affinity (-6.890 kcal/mol) to target but could not make mandatory hydrogen bonds with enzyme for demonstrating inhibitory activity and made hydrogen bonds with ASP187 and GLU192 amino acids residues of enzyme and revealed quite similar conformational changes in the target enzyme (see figure 4b).
Therefore, Berberine and Luteolin could not be used as inhibitors of main protease enzyme.
Sanguinarine also demonstrated a good binding energy but could not afford any hydrogen bond with virus enzyme. Embelin, Capsaicin, Emodin and Gossypol were found to be in the active site and interacted with enzyme through requisite hydrogen bonds but could not exhibit good binding affinity toward target enzyme (-4.940 kcal/mol, -5.510 kcal/mol, -6.490 kcal/mol and -6.290 kcal/mol respectively). Hypericin is a naphthodianthrone, an anthraquinone derivative expressed better binding affinity i.e. -9.050 kcal/mol but made unsuitable hydrogen bond with ASN142 residue in the active site of target enzyme also made a necessary hydrogen bond with HIS 164 residue required for enzyme inhibition.Oxyacanthine displayed the highest binding affinity those of among other ligands involved in the study i.e. -10.990 kcal/mol and produced in the significant changes in the conformations of main protease enzyme (see figure.11b).
\n\nCONCLUSION\nA new strain of coronavirus has now been extended from Wuhan city of China to the other parts of world for which not any approved medications are existed. Therefore, from the current molecular docking study it has been concluded that Oxyacanthine can act as Mpro inhibitor but need to be explored for more experimental work regarding development of anti SARS-Mpro inhibitor.
", "answer": "Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process.", "id": 159} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presentation while feeding the horse .\nthere was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm .\ncopious irrigation with normal saline was done and he was administered anti - tetanus and postexposure rabies prophylaxis .\nhe underwent emergency wound debridement , and the ulna was stabilised with an intra - medullary square nail .\nhe had an uneventful recovery and at three - month follow - up , the fractures had healed radiographically in anatomic alignment . at two - year follow - up , he is doing well , is pain free and has a normal range of motion compared to the contralateral side .\nhorse bites behave as compound fractures however rabies prophylaxis will be needed and careful observation is needed .\nearly radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .\nfalls and kicks are common mechanism of injuries in people handling horses [ 1 - 3 ] .\nwe present a case of forearm open fracture due to horse bite and its management .\na 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presenting to us .\nhe had recently bought the horse for renting it for marriages and other social and religious functions . on examination , there was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm .\n1(a ) and ( b ) ) front and dorsal view of the forearm on presentation showing the bite wounds .\nhe was given 0.5 ml tetanus toxoid and 500 iu tetglob ( human tetanus immunoglobulin bp ) , and received post - exposure rabies prophylaxis with vaxirab ( purified duck embryo vaccine for rabies ip ) .\nradiographs revealed fracture of radius and ulna in the mid - shaft region ( fig .\nhe was taken to the operating room ( or ) where careful debridement of the wounds was done under loupe - magnification .\nthe ulna was stabilised with an intra - medullary talwalkar square nail ( inor , mumbai , india ) .\nseventy - two hours later , he was taken to the or for re - debridement .\nthe nail in ulna was removed and conversion osteosynthesis using dynamic compression plate and screws for radius and ulna was done ( fig .\nhe was changed to oral cephalexin and ciprofloxacin on day 6 which were given till suture removal .\nhe had an uneventful recovery and was discharged from the hospital on the 10th day from injury .\nthe patient , however , sold the horse as he was too scared to keep it . at three - months\nthree - month follow - up radiographs showing fracture healing in anatomic alignment . at two - year follow - up\n, he is doing well , is pain free and has a normal range of motion compared to the contralateral side .\nhe is able to use his hand for all routine work and has returned to his work in the farm .\nin horse - related accidents , the majority of injuries occur when the person falls from a horse [ 1 - 3 ] .\nblow by a horse , getting struck by an object while riding a horse , being kicked by a horse , the horse falling on the patient , being entangled by reins , and being bitten by a horse are other less common horse - related accidents .\nmost people bitten by horses do not seek medical advice as most bite injuries are minor and self - treated or do not require admission to hospital .\nthomas et al in their study estimated that 102,900 people are treated yearly in emergency rooms in the us due to nonfatal horse related injuries , and about 1800 patients are treated each year after horse bites .\nour patient was too frightened to keep the horse and risk another bite , and hence , sold it not caring for the implications of financial loss .\ndomestic animals at home differ between societies , and therefore , local traditions affect the epidemiology of animal - related injuries . comparing animal bite wounds , cat bites result in punctured deep wounds , dog bites cause rather superficial abrasion and laceration type wounds ; because of the great deal of force exerted by an equine in closing its jaws , in horse and donkey bites , the severity of injuries may range from mild superficial pressure trauma , cutaneous breaks of the skin , deep lacerations with loss of tissue , to amputations of digits and even the nose .\npeel et al reported a case of fracture of the forearm bones following horse bite that was treated with open reduction and internal fixation primarily .\nhe sustained repeated infections with purulent wound discharge from which mixed cultures of bacteria , including staphylococcus aureus , prevotella melaninogenica , escherichia coli , and pasteurella multocida were isolated .\nmore than 3 months after the initial attack by the horse actinobacillus suis was isolated by bone biopsy specimen . though the acute trauma is readily apparent from a biting event ,\nthere is also the risk of exposure to various microbes in the oral secretions of equines .\ntransmission of such agents with zoonotic potential can also occur from the non - bite exposures to the oral and respiratory secretions .\nbecause of the large number of bacteria in the mouth , animal bite wounds are generally contaminated and their treatment is difficult , particularly in extensive lesions .\nthe occurrence of bacterial infection after animal bites depends on several factors , such as species of animal aggressors ( humans would be associated with a higher infection risk ) , type and site of the injuries ( wounds located in hands have a higher infection risk ) , care given to the wound , inherent factors in the individual ( greater risk in elderly , those with diabetes mellitus , vascular disease , etc ) . in relation to wound type , puncture wounds\nhave been reported to have a higher infection rate after animal bites , possibly due to the deposition of bacteria deep in the skin .\nthere is evidence that the use of antibiotic prophylactic after bites of the hand reduces infection .\nhorse bites most commonly lead to infections with burkholderia , streptococcus , staphylococcus , rhodococcus , actinobacillus , yersinia , and pasteurella , escherichia , neisseria , prevotella , pseudomonas , listeria , hendra virus , vesicular stomatitis virus species .\nbites , kicks or strikes , animal contact and cutting or scratching were the most frequent mechanisms of injury reported .\nnearly 20% of reported horse - related injuries , 14% of cattle and cats and 11% of dog - related injuries resulted in admission .\nbrouwer et al reported a case of streptococcus equi meningitis complicated by brain abscesses , as a result of a horse bite .\nkse et al performed a retrospective evaluation of 24 patients presenting with animal bites ( 19 horse and 5 donkey bites ) .\nthe head and neck were the most frequent bite sites ( 14 cases ) , followed by the extremities ( eight cases ) and the trunk ( two cases ) .\nour primary aim was damage - control to aggressively debride and at the same time give stability to the limb for wound dressings .\npreliminary stabilisation of the forearm by an intramedullary talwalkar square nail ( inor , mumbai , india ) in the ulna was done following debridement of the wounds and excision of devitalised tissues . fixing the ulna with a nail also helped in maintaining forearm length .\nre - debridement at 72 hours , showed no features of infection and decision of internal fixation with plate and screws was taken .\nwe also wish to highlight to the journal reader community that putting in implants when there is any doubt of contamination is risking long term bone infection and other associated complications of delay - in - union and non - union with compromised hand function .\nintra - medullary nail was preferred over external fixator in this case , though in fractures with severe soft tissue damage the use of external fixator is indicated .\nthe problems of using external fixation in the forearm include : pin - track - infection , nerve damage due to insufficient anatomical exposure and a relatively high rate of non - union .\nconversion osteosynthesis to internal fixation after primary external fixation is associated with high rates of osteomyelitis .\nplating is established as the standard method in the operative treatment of forearm fractures in adults .\nwe successfully converted the fixation from intra - medullary nail to plating with no incidence of infection or delay - in - union .\ntherefore , it makes sense to debride wounds which have necrotic tissue early rather than later .\nconsidering the most common complication of zoonotic infection related to animal bite injuries , our successful surgical treatment without complication appears to have definite clinical relevance .\nthe systematic treatment protocol of early radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .\nhorse or other animal bites are uncommon injuries . the management of these cases should be staged with the principles of damage control and infection control taking precedence . through this publication\nwe wish to highlight these rare injuries in the orthopaedic community and the journal readers .", "answer": "introduction : fractures have been described mainly following falling accidents in horse - related injuries . \n horse bites are uncommon accidents . \n we present a case of open fracture of the forearm due to horse bite.case report : a 35-year - old male farm - worker presented to the emergency room with alleged history of horse bite to the right forearm about 2 hours prior to presentation while feeding the horse . \n there was deformity of the forearm with multiple puncture wounds , deep abrasions and small lacerations on the distal - third of the forearm . copious irrigation with normal saline was done and he was administered anti - tetanus and postexposure rabies prophylaxis . \n prophylactic antibiotic therapy was commenced . \n radiographs revealed fracture of radius and ulna in the mid - shaft region . \n he underwent emergency wound debridement , and the ulna was stabilised with an intra - medullary square nail . \n seventy - two hours later , he underwent re - debridement and conversion osteosynthesis . \n he had an uneventful recovery and at three - month follow - up , the fractures had healed radiographically in anatomic alignment . at two - year follow - up , he is doing well , is pain free and has a normal range of motion compared to the contralateral side.conclusion:horse bites behave as compound fractures however rabies prophylaxis will be needed and careful observation is needed . \n early radical debridement , preliminary skeletal stabilisation , re - debridement and conversion osteosynthesis to plate , and antibiotic prophylaxis were the key to the successful management of our patient .", "id": 160} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngastric volvulus is characterized by a rotation of the stomach along its axis in variable degrees and may present either acutely or chronically .\nit may cause a complete gastric outlet obstruction and strangulation , leading to ischemic necrosis and perforation with a mortality rate of 3050% .\nprimary gastric volvulus results from abnormalities of the four gastric ligaments that restrict rotation : gastrocolic , gastrophrenic , gastrosplenic and hepatogastric .\nwe report a case of a gastric volvulus in a patient with a history of a diaphragmatic hernia .\nan emergent laparoscopic diaphragmatic hernia mesh repair and gastropexy was performed , resulting in a complete recovery .\na 49-year - old woman presented to our emergency department with a 2-week history of epigastric pain and vomiting with no prior trauma . her past medical history included hypertension , iron deficiency anemia , laparoscopic cholecystectomy and an open uterine myomectomy .\nupon arrival to the emergency department , she had a pulse of 135 beats per minute , a blood pressure of 110/90 mmhg , a respiratory rate of 20/min , a body temperature of 37.6c and an oxygen saturation of 98% on room air .\nher clinical examination revealed tenderness over the epigastric region , and her bowel sounds were hyperactive . she had decreased air entry at the left basal region of the chest .\nthe initial laboratory results were white blood cell count 22.1 10/l ( neutrophilic ) , blood urea nitrogen 7.8 mmol / l , creatinine 121 umol / l and normal liver function tests , amylase and lipase .\na chest radiograph demonstrated a significant air - fluid level near the left lung base ( fig . 1 ) . \n\nfigure 1:chest x - ray showing an elevated air - fluid left in the left basal lung region .\nchest x - ray showing an elevated air - fluid left in the left basal lung region .\ntwo days prior to her admission , she had undergone upper gastrointestinal endoscopy for the same complaint in another center that revealed a dilated gastric lumen with herniation of the distal stomach , pylorus and first part of the duodenum into the left hemi - thorax ( fig . 2 ) .\nresuscitation was commenced with immediate nasogastric decompression , intravenous hydration and analgesia , proton - pump inhibitors and electrolyte replacement .\na double contrast - enhanced computed tomography ( ct ) scan of the chest and the abdomen demonstrated a large diaphragmatic defect ( 7 7 cm ) and a left diaphragmatic hernia containing a dilated stomach , suggestive of a gastric outlet obstruction ( fig . \n3 ) . a water - soluble gastrografin meal was performed , showing an intra - thoracic , mesentero - axial gastric volvulus ( fig . \nfigure 2:flexible upper endoscopy showing herniation of the distal stomach , the pylorus and the first part of the duodenum into the left hemi - thorax . \n\nfigure 3:different views of a double contrast - enhanced ct scan showing a left diaphragmatic hernia with an acute dilated stomach . \n\nfigure 4:water - soluble gastrografin meal showing an intra - thoracic mesentero - axial volvulus .\nflexible upper endoscopy showing herniation of the distal stomach , the pylorus and the first part of the duodenum into the left hemi - thorax .\ndifferent views of a double contrast - enhanced ct scan showing a left diaphragmatic hernia with an acute dilated stomach . water - soluble gastrografin meal showing an intra - thoracic mesentero - axial volvulus .\nthe patient was listed emergently , underwent general anesthesia and was placed in a 30-degree split - leg reverse trendelenburg position .\na four - port approach was used after verres pneumoperitoneum was achieved . on inspection of the peritoneal cavity ,\nthe stomach and the first part of the duodenum were incarcerated in the peritoneal sac in the left hemi - diaphragm ( fig . \nthe rotated stomach and the first part of the duodenum were completely reduced from the thoracic cavity into the abdomen .\nonce the dissection of the sac was complete , we confirmed that there was no visceral injury and proceeded to repair of the 7 7 cm diaphragmatic hernia ( fig . \na gore bio - a tissue reinforcement absorbable mesh ( 15 12 cm ) was selected to encourage the formation of vascularized neotissue .\nit was fixed in place using ethicon securestrap absorbable strap fixation device ( fig . \na gastropexy was then performed to the anterior abdominal wall using a 2 - 0 polypropylene suture . \n\nfigure 5:laparoscopic view showing the incarcerated content in the peritoneal sac with a twisted stomach . \n figure 6:laparoscopic view showing a large ( size 7 7 cm ) diaphragmatic defect . \n\nfigure 7:laparoscopic view showing the primary closure of the diaphragmatic defect using an interrupted pds ii suture . \n\nfigure 8:laparoscopic view showing bio - a tissue reinforcement absorbable mesh ( size 15 12 cm ) fixed intraperitoneally below the defect .\nlaparoscopic view showing the primary closure of the diaphragmatic defect using an interrupted pds ii suture .\nlaparoscopic view showing bio - a tissue reinforcement absorbable mesh ( size 15 12 cm ) fixed intraperitoneally below the defect . on the first post - operative day\n, a water - soluble meal study was repeated and revealed a marked regression of the stomach size and a normal intra - abdominal position of the stomach and the first part of the duodenum with no evidence of obstruction ( fig . \nthe patient had an unremarkable recovery and was discharged on post - operative day 3 .\nshe was followed up in clinic 2 weeks post - operatively , and a follow - up upper gastrointestinal endoscopy was performed , which showed normal anatomy to the second part of the duodenum ( fig . \nfigure 9:water - soluble gastrografin meal showing normal intra - abdominal position of the stomach . \n\na detailed history of the risk factors associated with gastric volvulus including previous surgical procedures , gastro - oesophageal reflux disease or history of trauma should be obtained .\nthe initial management includes nasogastric decompression ( endoscopically if necessary ) , fluid resuscitation and correction of electrolyte imbalances [ 1 , 6 ] .\nendoscopic decompression , de - rotation and percutaneous endoscopic gastrostomy ( peg ) fixation of the stomach to the posterior abdominal wall are the first - line management for cases of primary gastric volvulus .\nit is also employed in cases of secondary gastric volvulus who are unfit for surgical repair under anesthesia .\nthe use of two peg tubes is optimal as the stomach may still rotate over a single peg .\nsurgical intervention is the treatment of secondary gastric volvulus and cases of volvulus in which an endoscopic or nasogastric decompression and de - rotation have failed .\nthere are no randomized control trials available ; however , observational studies support laparoscopy for its benefits of reduced inpatient stays and improved post - operative morbidity\n. a recurrence rate of 42 vs. 15% post laparoscopic and open gastropexy , respectively , has been described in one study .\nhowever , it is important to stress that this is for gastric fixation alone and does not compare recurrence rates after hernia repair .\nthe laparoscopic approach is defined by the need to de - rotate and reduce the gastric contents into the abdominal cavity .", "answer": "gastric volvulus is an uncommon but serious surgical condition mandating an early diagnosis and surgical intervention . \n it may present either acutely or chronically with epigastric pain , retching and vomiting . \n there are two types of gastric volvulus : organo - axial and mesentero - axial . \n we report a case of a mesentero - axial gastric volvulus in a 49-year - old woman with a left - sided diaphragmatic hernia . \n she presented with a significant epigastric pain and vomiting . \n a flexible upper endoscopy , a barium meal and a contrast - enhanced computed tomography imaging had confirmed the diagnosis . \n she was treated with a laparoscopic mesh repair of the diaphragmatic defect followed by a gastropexy . \n she had an uneventful postoperative course and was asymptomatic thereafter .", "id": 161} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe assessment of intravascular volume and the adequacy of volume resuscitation are among the most difficult clinical challenges .\nsystolic blood pressure , heart rate and urine output change minimally in early hemorrhagic shock .\nhypotension , tachycardia , cold extremities , decreased urine output and poor capillary refill are only present in patients who have lost in excess of 30% of their blood volume ( classiii hemorrhage ) .\nfurthermore , both the central venous pressure and the changes in the central venous pressure in response to volume loading are poor indicators of intravascular volume and recruitable cardiac index .\nwhile flow to the brain and the myocardium is preserved in patients with ' compensated shock ' , splanchnic and renal perfusion may be seriously compromised .\nsplanchnic hypoperfusion leads to both functional and structural changes in the gut mucosa , with increased permeability and translocation of bacteria and bacterial products .\nincreased mucosal permeability has been strongly associated with the development of the multiorgan dysfunction syndrome .\nthe expedient detection and correction of tissue hypoperfusion associated with ' compensated shock ' may limit organ dysfunction , may reduce complications and may improve patient outcome .\nit is probable that the earlier tissue hypoperfusion is detected and corrected , the greater the likelihood that outcome will be improved .\nindeed , rivers and colleagues reported a 32% relative reduction in the 28 day , all cause mortality of patients with severe sepsis who received early aggressive volume resuscitation in the emergency department .\nused the central venous oxygen saturation as the endpoint of resuscitation in the intervention group , while treatment in the control group was guided by standard clinical endpoints including the central venous pressure .\nwhile their study clearly demonstrates the value of early aggressive volume resuscitation , the use of central venous oxygen saturation to guide early resuscitation is not practical and has important limitations .\nthe base excess ( be ) has become the standard endpoint of resuscitation in trauma patients .\nremarkably , while the be has been demonstrated to be of prognostic value , it has never been assessed prospectively in trauma patients .\nthe use of the be is based on the principle that tissue hypoxia associated with poor perfusion will result in the generation of hydrogen ions and a metabolic acidosis .\nhowever , it is probable that tissue hypoperfusion may occur in the absence of a significant change in the be .\nfurthermore , as significant time is required for the liver and kidney to regenerate bicarbonate , it can be expected that there will be a long lag phase between the correction of intravascular volume and normalization of the be .\nboth of these assumptions are elegantly demonstrated in the study by totapally and colleagues reported in the present issue of critical care . in a rat hemorrhage model these authors demonstrated that the be responded slowly to changes in intravascular volume and that there was a significant increase in the be only when the mean arterial blood pressure fell by greater than 50% .\nhowever , totapally etal . demonstrated that changes in the esophageal carbon dioxide gap closely mirrored changes in the intravascular volume .\nsimilar findings have been reported by other investigators . in patients with penetrating trauma , baron and\ncolleagues demonstrated that sublingual carbon dioxide measurements correlated well with the degree of blood loss .\nboth ivatury and colleagues and kirton and coworkers have demonstrated that gastric intramucosal ph correlates well with the degree of injury and that optimizing the gastric intramucosal ph in the first 24 hours following trauma is associated with a reduction in the incidence of organ failure and death .\nthe study by totapally and colleagues suggests that the be is an insensitive indicator of the degree of the intravascular volume deficit following hemorrhage and that it responds slowly to volume resuscitation .\nesophageal and sublingual capnometry , however , appear to provide near instantaneous information regarding the degree of the volume deficit and the adequacy of volume resuscitation .\nthis technology is simple and noninvasive , and is ideally suited for use in the emergency room and the trauma bay .\nthe esophageal or sublingual pco2 gap may prove to be a useful endpoint for the resuscitation of trauma victims .\nthe author has received a research grant from optical sensors inc , minneapolis , mn , usa , the manufacturer of the nellcor n-80 capnoprobe sl device .", "answer": "although it has never been prospectively validated , the base excess ( be ) is regarded as the standard end - point of resuscitation in trauma patients . in a rat hemorrhage model , in this edition of critical care , totapally and colleagues demonstrate that the be is an insensitive and slowly responsive indicator of changes in intravascular volume . \n this contrasts with changes in the esophageal - arterial carbon dioxide gap which more closely followed changes in blood volume . \n esophageal or sublingual capnometry may prove to be a useful tool for monitoring the adequacy of resuscitation in trauma victims .", "id": 162} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSolid-Phase Synthesis of 2-Aminobenzothiazoles\n\nPaper sections:\n\nLibraries of compounds based on diverse heterocyclic scaffolds comprise a key aspect of modern drug discovery. In this context, solid supported synthesis has proved to be a powerful tool leading to a wide-range of heterocyclic compounds.1 However, to the best of our knowledge, a procedure for the solid phase synthesis of 2-aminobenzothiazoles has not been reported. The 2-aminobenzothiazole scaffold is one of the \"privileged\" structures in medicinal chemistry.2 Indeed, various examples featuring this particular scaffold have been prepared, many exhibiting remarkable biological activities.3,4 Given the importance of this particular chemical entity to the field of medicinal chemistry, the development of improved and/or alternative methods for the rapid construction of libraries of derivatives is desirable. Although examples of solid supported synthesis of benzothiazoles have been reported,5,6 these methods are not applicable to 2-aminobenzothiazoles. We thus undertook a focused study to adapt previously disclosed methods for solution phase synthesis to the solid phase for this particular class of heterocycles.
The now classical synthesis of 6-substituted 2-aminobenzothiazoles entails treatment of 4-substituted anilines with potassium thiocyanate in the presence of bromine in acetic acid (Scheme 1 A).7 This method, however, is not generally applicable as thiocyanation in the para position of anilines is often the predominant reaction when 4-unsubstituted anilines are employed under these or similar oxidation conditions (Scheme 1 B).8,9 Alternative methods for the syntheses of 4, 5, 6, and 7 substituted 2-aminobenzothiazoles employ phenylthioureas as the synthetic precursors (Scheme 1 C). In these cases, heterocycle ring formation can be carried out, albeit non regioselectively, by treating the phenylthioureas with bromine in chloroform10 or acetic acid.11 Alternatively, regiospecific cyclizations can be performed via SNAri reactions, employing phenylthioureas obtained from the appropriate ortho-fluoroanilines in the presence of sodium methoxide.12 We report here adaptation of these reaction conditions onto solid support beginning with resin-bound isothiocyanate.
The resin-bound isothiocyanate 3 was prepared as previously described in two steps from carboxy-polystyrene (Scheme 2).13 Conversion of 3 to the N-acyl, N\u2032-phenylthioureas of general structure 4 was then readily achieved upon treatment of 3 with the appropriate aniline at room temperature in N,N-dimethylformamide.14 This reaction can be conveniently monitored by infrared spectroscopy following the disappearance of the characteristic isothiocyanate band at \u223c1910 cm-1 (Figure 1). When X = H cyclization of 4 to 2-acylaminobenzothiazole 5 was then performed by treatment with six equivalents of bromine in acetic acid (Scheme 2, Method A14). Alternatively, when X = F or Br, benzothiazoles obtained (e.g., entries e, and h Table 1), were formed by treatment of the corresponding N-acyl, N\u2032-phenylthioureas with sodium hydride (Method B & C14) via an SNAri mechanism.
Finally, the desired 2-aminobenzothiazoles of general structure 6 were obtained in good overall yield and >85% purity upon treatment of 5 with 4% hydrazine monohydrate in ethanol (Table 1).14 Alternative TFA-mediated cleavage conditions were also investigated, however, the optimized hydrazine cleavage conditions proved more reliable, and generally proceeded with little or no trace of contaminants or by-products (cf., Figure 2).
As anticipated, when 3-subtituted anilines (e.g., entries c and f, Table 1) were employed, oxidative cyclization conditions (Method A) led to mixtures of two regioisomers (i.e., 5- and 7-substituted 2-aminobenzothiazoles); the relative ratio apparently determined by the steric encumbrance of the substituent in the meta position of the starting aniline. Thus, while 3-bromoaniline furnished a separable 1:1 mixture of 5- and 7-bromo-2-aminobenzothiazoles, under the above reaction conditions, the 3-phenylaniline generated a mixture (95:5) in favor of the 5-substituted-2-amino-benzothiazole (cf., entries c and f, Table 1), which could be readily separated and purified by column chromatography or crystallization. Single crystal X-ray analysis confirmed the structure of 6f (Figure 3).
Although mixtures of regioisomers are often acceptable in the generation of libraries for HTS, single isomers could be obtained when ring formation was performed via SNAri, as exemplified by entries e (Method B) and h (Method C); each proceeded regiospecifically to furnish the 7-chloro- and the 5-bromo-2-aminobenzothiazole 6e and 6h (Table 1), respectively.
Finally, in order to exemplify the utility of this synthetic protocol for the construction of libraries of 2-aminobenzothiazole derivatives, we evaluated representative resin-bound bromobenzothiazoles 5c and 5h as possible starting points for further structural elaboration. Thus, 5c and 5h were treated under either Suzuki15 or Buchwald-Hartwig16 conditions to yield products of cross-coupling. Representative examples of C\u2013C, and C\u2013N bond forming reactions are summarized in Table 2.
Both cross-coupling reactions were carried out under microwave promoted conditions. For these reactions, 0.05-0.1 mol% of Pd(PPh3)4 was found to be the preferred catalyst (cf., Table 3).
In summary, we have developed an effective method for the solid supported synthesis of 2-aminobenzothiazoles, with an application to the preparation of a focused library of 2-aminobenzothiazole derivatives.
IR spectra.
LC/MS Analysis of the crude reaction obtained after hydrazine-mediated cleavage (entry f, Table 1); A: photodiode array detector; B: total ion current; C: mass spectrum.
X-ray crystal structure of compound 6f (CCDC 753930).
Commonly employed methods for the solution phase synthesis of 2-aminobenzothiazoles (A and C); thiocyanation of 4-unsubstituted anilines upon treatment with potassium thiocyanate in the presence of bromine in acetic acid (B).
Reagents and Conditions: (a) oxalyl chloride, DCE, rt, 16 h; (b) Bu4NNCS, DCE/THF, rt, 16 h; (c) aniline, DMF, rt, 16 h; (d) For X = H, Method A: Br2 (6 eq.), acetic acid, rt, 16 h; for X = F, Method B: NaH (6 eq.), DMF, rt, 16 h; for X = Br, Method C: NaH (10 eq.), DMF, 100 \u00b0C, 16 h (e) hydrazine monohydrate, EtOH, 150 \u00b0C, MW, 30 min.
Representative examples of 2-aminobenzothiazoles prepared.
Overall yield after purification.
Approximately a 50:50 mixture of 5- and 7-bromo-2-aminobenzothiazoles;
Approximately a 95:5 mixture of 5- and 7-phenyl-2-aminobenzothiazole.
Representative examples of cross-coupling reactions.
Approximately a 50:50 mixture of 5- and 7-phenyl-2-aminobenzothiazoles (separable).
Cross-coupling reaction investigation.
Conversion of the starting material by LC-MS analysis after cleavage of the product.
", "answer": "A traceless solid supported protocol for the synthesis of 2-aminobenzothiazoles is described, employing resin-bound acyl-isothiocyanate and a series of anilines. Cyclization of the resulting N-acyl, N\\xe2\\x80\\xb2-phenyl-thioureas generates the 2-aminobenzothiazole scaffold, which can be further elaborated prior to hydrazine-mediated cleavage of the final products from the carboxy-polystyrene resin. A small, focused library of 2-aminobenzothiazoles was prepared.", "id": 163} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nspasticity is a frequent consequence of stroke1 , \n 2 . in the lower leg ,\nthis malposition or \n malalignment causes mechanical stress to foot joints in the lateral forefoot area , and \n joints under this stress are likely to be inflamed and painful4 .\nfoot pain causes difficulty in standing and walking , and thus \n limits daily living activities .\nthe malposition or malalignment of the foot can be managed by the \n control of spasticity .\nit was proposed that correcting the malposition or malalignment can \n reduce abnormal mechanical pressure in specific areas of the foot , which leads to a \n reduction in foot pain . of the several options available for the management of spasticity\n, \n the clinical usefulness of nerve and motor point blocks with alcohol has been well \n demonstrated5,6,7 . in the current study , whether a reduction of ankle spasticity using nerve and motor point \n blocks with 20% ethyl alcohol can manage foot pain was examined .\na 58-year - old woman visited the rehabilitation department of a university hospital due to \n piercing pain ( numeric rating scale [ nrs ] : 8) in the left fifth metatarsal head for two \n years .\nerythema and edema were present on the lateral aspect of the head of the fifth \n metatarsal bone ( fig .\n1.(a ) an image of the patient s left foot shows erythema and edema \n in the fifth metatarsal head area .\n( b ) the left foot x - ray showed that the fourth and \n fifth intermetatarsal angle was 7.7 ) . the patient provided informed signed consent \n for participation in the study .\nthe study was approved by the research ethics committee of \n yeungnam university hospital ( yuh-16 - 0425-d7 ) . on the foot x - ray ,\nthe fourth and fifth \n intermetatarsal angle of the left foot was 7.7 ( fig . \n\nshe had a history of intracerebral \n hemorrhage on the right basal ganglia about five years previously .\nthe degree of her spasticity was a modified \n ashworth scale ( mas)8 of 1 + .\nadditionally , slight motor weakness ( medical \n research council9 : 4 + ) in the left upper \n and lower extremities was shown .\nother neurological symptoms , including sensory and \n cognitive deficits , were not present . at first , 0.5 ml of 2% lidocaine with 10 mg \n triamcinolone acetonide was injected into the tender point of the left fifth metatarsal head \n area .\n( a ) an image of the patient s left foot shows erythema and edema \n in the fifth metatarsal head area .\n( b ) the left foot x - ray showed that the fourth and \n fifth intermetatarsal angle was 7.7 it was proposed that the ankle spasticity in the patient caused repetitive pressure and \n shearing between the soft tissue and head of the fifth metatarsal bone .\nthus , we considered \n the possibility that controlling spasticity might be helpful in the management of pain from \n the tailor s bunion , and decided to control spasticity in this patient using a nerve or \n motor point block with 20% ethyl alcohol . to reduce the spasticity of the left ankle plantar \n flexor , the medial and lateral motor branches to the gastrocnemius muscle of the left tibial \n nerve\nthe block of nerve branches \n was performed based on the method described by jang et al5 . to manage spasticity in the left ankle supinator\na motor point \n block was performed in the left tibialis posterior muscle with 5 ml of 20% ethyl alcohol . \n\nboth nerve and motor points were \n located using the nerve stimulator at the popliteal area and at the mid - calf level , \n respectively .\nthe cathode stimulating needle ( teflon - coated , 23-gauge needle ) was slowly \n advanced in the direction of the nerve and posterior tibialis muscle .\nthe needle hub was \n connected to injection tubing that bore the syringe containing the 20% ethyl alcohol . \n\ncontractions were seen and palpated as the tip came close to the nerve or motor point of the \n tibialis posterior . at this stage ,\nthe intensity of the current was between 3 ma and 5 ma . \n after the needle was placed close to the targeted nerve or motor point ,\nthe tip is assumed to be in contact with the nerve or motor \n point when maximum contraction is obtained with minimum current .\nthe needle was finally \n positioned at a current of 1 ma with nerve block and 3.5 ma with motor point block . \n\nadditionally , the patient underwent the stretching exercises for the left ankle plantar \n flexors and ankle supinators for 2 weeks after the alcohol block ( monday through friday : 15 \n mins 1 time / day ) . to evaluate dynamic foot pressure , the foot pressure measurement system ( fpms ) ( tpscan ; \n biomechanics , goyang , korea ) was used10 . \n\ndynamic foot contact pressure data during gait were recorded on the fpms floor mat ( 40.5 \n 40.5 cm ) at the middle of the gait test .\nthe foot pressure was presented as a \n color : red is the highest pressure followed by orange , yellow , green , and blue .\nfoot contact \n pressure was evaluated twice before and one- month after the nerve and motor point block \n procedure . before the procedure\n, contact pressure was highly distributed to the lateral \n forefoot , however , reduced distribution was observed in the medial forefoot and hindfoot \n ( fig .\n2.foot \n pressure measurement imagethe foot pressure image of a normal foot and the \n images of the patient s foot pressure showing alterations pre - alcohol block and \n post - alcohol block . ) . \n\nafter the procedure , the distribution of foot contract pressure was found to be similar to \n that of a normal control ( 56-year - old female individual ) .\nfoot \n pressure measurement image the foot pressure image of a normal foot and the \n images of the patient s foot pressure showing alterations pre - alcohol block and \n post - alcohol block .\nat the follow - up evaluation , two weeks after the alcohol block , the spasticity in the left \n ankle plantar flexor and supinator had disappeared ( mas : 0 ) .\nin addition , ankle clonus was \n not present . moreover , the pain in the left fifth metatarsal head was significantly reduced \n from nrs 8 to nrs 1 . at one , two , and three\nmonths after the alcohol block the effects on \n ankle spasticity and foot pain were sustained .\nin the present study , foot pain related to tailor s bunion was reduced after spasticity \n treatment using nerve and motor point block with 20% ethyl alcohol .\nalthough the incidence of foot pain in patients with stroke has not been investigated , \n patients with stroke are prone to have foot pain due to deteriorated musculoskeletal \n position or alignment induced by spasticity or motor weakness .\nthe tailor s bunion or \n bunionette , which was first described by davies in 194911 , is a painful bony prominence on the lateral , dorsolateral , or \n plantar aspect of the head of the fifth metatarsal bone12 .\nthe conflict between the fifth metatarsal head and footwear has \n been reported to be the cause of tailor s bunions12 . in the patient ,\nthe spasticity in the ankle plantar flexor and \n supinator appeared to cause repeated mechanical stress and chronic irritation in the fifth \n metatarsal head area , which is thought to induce a tailor s bunion . for the management of foot pain due to tailor s bunion , corticosteroids were injected into \n the tender point of the fifth metatarsal head area ; however , the patient s pain was \n unresponsive to this injection .\nit was considered that non - controlled spasticity can lead to \n continuous mechanical stress or irritation and repeated occurrence of inflammation in the \n fifth metatarsal head area .\ntherefore , the spasticity was controlled using a block with 20% \n ethyl alcohol on the motor branches to the gastrocnemius muscle of the tibial nerve and the \n motor points of the posterior tibialis muscle .\nafter the block with ethyl alcohol , spasticity in this \n patient had almost disappeared ( from mas 1 + to mas 0 ) .\nalso , the patient received the \n stretching exercises for the ankle plantar flexors and the ankle supinators .\nthe stretching \n exercise is known to effectively reduce spasticity13 , \n 14 by increasing tissue \n extensibility15 .\nit was thought that \n the reduced spasticity in the patient was attributed , at least in part , to the stretching \n exercises .\nit is thought that the mechanical stress and irritation in the fifth metatarsal \n head area during walking were significantly reduced with the disappearance of spasticity in \n this patient .\nwhen the stress and irritation were reduced after the management of \n spasticity , the pain due to tailor s bunion appeared to be significantly reduced .\nin addition , the fpms was used for detailed evaluation of the effect of the 20% ethyl \n alcohol block . before the alcohol block ,\nafter the control of spasticity with the alcohol \n block , increased contract foot pressure in the hindfoot and medial forefoot were observed . \n\nthis change in pressure distribution is concurrent with the results of several previous \n studies10 , 16 , 17 . using fpms ,\nit was \n confirmed that mechanical stress abnormally concentrated on the fifth metatarsal head area \n was corrected to near normal following the alcohol blocks on the tibial nerve branches and \n the motor point of the tibialis posterior muscle .\nthe correction of foot contact pressure \n distribution appears to have contributed to the pain reduction in the fifth metatarsal head \n area . in conclusion ,\nthe case of a patient with chronic hemiparetic stroke whose pain due to \n tailor s bunion showed relief following the control of spasticity using nerve and motor \n point blocks with 20% ethyl alcohol was reported .\nthis study showed that deteriorated foot \n position or alignment induced by spasticity and malposition / malalignment - related foot pain \n can be successfully managed by nerve and motor point blocks with 20% ethyl alcohol . on the \n basis of the clinical experience in this study ,\nwhen clinicians treat foot pain in patients \n with stroke , they should consider the possibility that spasticity can contribute to the \n development of foot pain .\nthis is first study to show that management of spasticity can \n reduce foot pain in a patient with hemiparetic stroke . however , since this study reports a \n single case , further studies involving a larger number of patients are necessary .", "answer": "[ purpose ] this study report a case of a patient with hemiparetic stroke who showed \n significantly reduced foot pain when ankle spasticity was reduced using nerve and motor \n point blocks with 20% ethyl alcohol . \n [ subject and methods ] a 58-year - old woman with left \n hemiparesis following intracranial hemorrhage five years previously presented with pain in \n the left fifth metatarsal head for two years ( numeric rating scale[nrs ] : 8) . \n erythema and \n edema were observed on the lateral aspect of the head of the fifth metatarsal bone . \n she \n was diagnosed with a tailor s bunion . \n spasticity was observed in the left ankle plantar \n flexor and ankle supinator ( modified ashworth scale : 1 + ) . using 20% ethyl alcohol , a block \n in the medial and lateral motor branches to the gastrocnemius muscle of the left tibial \n nerve and the motor point of the left posterior tibialis muscle was performed . \n [ results ] \n after the alcohol block , spasticity had almost disappeared and foot pain was significantly \n reduced ( nrs : 1 ) . \n results from the foot pressure measurement system test showed foot \n contact pressure was highly distributed to the lateral forefoot pre - block . \n after the \n block , the distribution of foot contract pressure was similar to normal distribution . \n \n [ conclusion ] clinicians should consider the possibility that spasticity can contribute to \n foot pain .", "id": 164} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlower urinary tract symptoms ( luts ) due to benign prostatic hyperplasia ( bph ) are one of the most common diseases in elderly males .\npatients in general are prescribed an alpha - blocker first and then , if necessary , are treated by transurethral resection of the prostate ( turp ) if not enough response to the alpha - blocker is shown .\nturp has been accepted as the gold standard for the surgical management of symptomatic bph . even though several excellent alpha - blockers are in use , some patients with severe luts require surgical therapy .\nour county 's guidelines recommend surgical management for patients with bph with repeated urinary retention or bladder stone formation .\nrecently , surgical therapy has come to include methods thought to be relatively less invasive than turp .\nthese new methods have resulted in lower morbidity and excellent improvements in voiding and storage symptoms .\nfor example , holmium laser enucleation of the prostate ( holep ) has become a widespread and well - accepted treatment modality with excellent outcomes compared to other conventional treatment modalities such as turp and open prostatectomy . because this surgical procedure is comparatively new ,\nsurgeons tend to concentrate on the completion of the surgery , and most previous reports regarding holep have described the efficacy of the procedure for patients ' urination . as a next step , surgeons need to consider whether this procedure can be performed safely with a comparatively lower rate of adverse events than turp .\nthis new technique should not only be less invasive and offer better efficacy for urination but also show a lower ratio of adverse events , especially in terms of postoperative infectious diseases . in this study\n, we retrospectively examined the incidence of postoperative infectious complications ( pics ) in our early experience with holep for bph with a particular focus on the kind and duration of prophylactic antibiotic administration ( paa ) .\na retrospective study was conducted in 90 patients complaining of luts who underwent holep combined with morcellation at our institute between february 2008 and march 2011 .\nbriefly , a modified 26-fr continuous - flow resectoscope ( karl storz gmbh & co. , tuttlingen , germany ) was used for enucleation of the prostate . a 550-m end - firing laser fiber ( slimline 550 ; lumenis inc . , yoqneam , israel )\nwas engaged with an 80 w holmium : yttrium - aluminum - garnet laser ( versapulse select , lumenis inc . ,\nenergy power was usually set at 72 to 80 w ( 1.8 to 2.4 j and 30 to 40 hz ) and at 0.2 j and 40 hz for hemostasis .\ntissue morcellation was performed with a versacut morcellator ( versacut system , lumenis inc . ) through a 6-degree rectangular nephroscope ( karl storz gmbh & co. ) . during the transurethral procedure ,\nthe outer sheath was always in the urethra , because the resectoscope and nephroscope were exchangeable in the outer sheath .\nafter completion of the morcellation , a urethral catheter was inserted for continuous bladder irrigation with normal saline .\nthe kind and the dosing duration of paa were based on the physicians ' discretion .\npics were diagnosed according to the centers for disease control and prevention ( cdc ) guidelines ; in short , a pic was defined as a febrile ( body temperature 38 ) complication caused by a surgical procedure at a surgical site , such as urinary tract infection ( uti ) , that occurred within 30 days after surgery .\nwe analyzed the relationship between the emergence of pics and the kind or duration of paa .\nstatistical analysis was conducted with the jstat java virtual machine statistics monitoring tool with use of the chi - square test ( sun microsystems inc . , santa clara , ca , usa ) .\na retrospective study was conducted in 90 patients complaining of luts who underwent holep combined with morcellation at our institute between february 2008 and march 2011 .\nbriefly , a modified 26-fr continuous - flow resectoscope ( karl storz gmbh & co. , tuttlingen , germany ) was used for enucleation of the prostate . a 550-m end - firing laser fiber ( slimline 550 ; lumenis inc . ,\nyoqneam , israel ) was engaged with an 80 w holmium : yttrium - aluminum - garnet laser ( versapulse select , lumenis inc . ,\nenergy power was usually set at 72 to 80 w ( 1.8 to 2.4 j and 30 to 40 hz ) and at 0.2 j and 40 hz for hemostasis .\ntissue morcellation was performed with a versacut morcellator ( versacut system , lumenis inc . ) through a 6-degree rectangular nephroscope ( karl storz gmbh & co. ) . during the transurethral procedure ,\nthe outer sheath was always in the urethra , because the resectoscope and nephroscope were exchangeable in the outer sheath .\nafter completion of the morcellation , a urethral catheter was inserted for continuous bladder irrigation with normal saline .\nthe kind and the dosing duration of paa were based on the physicians ' discretion .\npics were diagnosed according to the centers for disease control and prevention ( cdc ) guidelines ; in short , a pic was defined as a febrile ( body temperature 38 ) complication caused by a surgical procedure at a surgical site , such as urinary tract infection ( uti ) , that occurred within 30 days after surgery .\nwe analyzed the relationship between the emergence of pics and the kind or duration of paa .\nstatistical analysis was conducted with the jstat java virtual machine statistics monitoring tool with use of the chi - square test ( sun microsystems inc . , santa clara , ca , usa ) .\ntwenty - three ( 25.6% ) had an indwelling catheter owing to urinary retention ( table 1 ) .\ndiabetes was seen in 19 patients ( 21.1% ) , heart disease in 17 ( 18.9% ) , and hypertension in 15 ( 16.7% ) .\nurological cancer was seen in 3 patients ( 2 patients had bladder cancer and 1 renal cancer ) .\nthere were 18 patterns regarding the kind and duration of paa ; the details are shown in table 3 .\nthe most frequently used paa was sulbactam / ampicillin ( sbt / abpc ; n=32 , 35.6% ) , followed by cefazolin ( n=18 , 20.0% ) and cefotiam ( n=9 , 10.0% ) .\nwe examined the influence of the kind or duration of dosing of paa on pcc occurrence .\nour statistical data showed that there were no significant differences between 2 or fewer days and 3 or more days of paa dosing with regard to pic occurrence .\nthere were also no significant differences between sbt / abpc , which was most frequently used in this study , and other antibiotics for paa with regard to pic occurrence ( tables 4 , 5 ) .\npic was diagnosed in 7 cases , and the paa of the cases was 3 sbt / abpc , 2 tazobactam / piperacillin , 1 cefazolin , and 1 cefotiam ( table 4 ) .\nthere were 3 cases of prostatitis , 2 cases of pyelonephritis , and 2 cases of epididymitis .\none case was diagnosed as sepsis after prostatitis caused by klebsiella pneumoniae and was cured by use of doripenem , cefazolin , and levofloxacin . in all , 2 cases of serratia marcescens , 1 case of proteus mirabilis , and 1 case of k. pneumonia were cultured , and these were quite different from the preoperative culture data shown above , which suggested that preoperative treatments might be effective ( table 6 ) .\ntwenty - three ( 25.6% ) had an indwelling catheter owing to urinary retention ( table 1 ) .\ndiabetes was seen in 19 patients ( 21.1% ) , heart disease in 17 ( 18.9% ) , and hypertension in 15 ( 16.7% ) .\nurological cancer was seen in 3 patients ( 2 patients had bladder cancer and 1 renal cancer ) .\nthere were 18 patterns regarding the kind and duration of paa ; the details are shown in table 3 .\nthe most frequently used paa was sulbactam / ampicillin ( sbt / abpc ; n=32 , 35.6% ) , followed by cefazolin ( n=18 , 20.0% ) and cefotiam ( n=9 , 10.0% ) .\nwe examined the influence of the kind or duration of dosing of paa on pcc occurrence .\nour statistical data showed that there were no significant differences between 2 or fewer days and 3 or more days of paa dosing with regard to pic occurrence .\nthere were also no significant differences between sbt / abpc , which was most frequently used in this study , and other antibiotics for paa with regard to pic occurrence ( tables 4 , 5 ) .\npic was diagnosed in 7 cases , and the paa of the cases was 3 sbt / abpc , 2 tazobactam / piperacillin , 1 cefazolin , and 1 cefotiam ( table 4 ) .\nthere were 3 cases of prostatitis , 2 cases of pyelonephritis , and 2 cases of epididymitis .\none case was diagnosed as sepsis after prostatitis caused by klebsiella pneumoniae and was cured by use of doripenem , cefazolin , and levofloxacin . in all , 2 cases of serratia marcescens , 1 case of proteus mirabilis , and 1 case of k. pneumonia were cultured , and these were quite different from the preoperative culture data shown above , which suggested that preoperative treatments might be effective ( table 6 ) .\nholep for bph has become widespread in the urological field and has recently been performed at many institutions .\nholep may involve less stress to patients and should offer a lower rate of surgical site infection and postsurgical complications than open surgery or turp .\nthis surgery has the benefit of less extensive injury to prostatic tissue than turp ; thus , postsurgical local inflammation may not be as severe as with turp .\ninflammation could be one risk factor for pics , such as prostatitis , and therefore holep may also be beneficial for suppressing pics . basically , holep is thought to cause the patients less stress in addition to having higher efficacy for luts .\nhowever , the present study had 7 cases of pics , and this ratio may be comparatively higher than in other reports .\nthere are several possible reasons for this ; 1 ) our 90 cases were performed by 7 surgeons including beginners with less than 5 cases of experience with holep .\neven though it is not clear whether there is a significant relationship between longer surgical time and a higher ratio of pic occurrence , beginners or less - experienced surgeons take more time to accomplish the surgery than experienced surgeons , both to finish the surgical procedures such as enucleation or tissue morcellation and to avoid surgery - related adverse events .\n2 ) paa may not have included the most appropriate kind of antibiotics or duration of dosing .\nthis is because the cdc guidelines and japanese guidelines recommend that first - generation cephalosporins be administered every 2 to 3 hours during surgery and that penicillins , first - generation or second - generation cephalosporins , and aminoglycosides be administered within 72 hours in turp , respectively .\nin addition , discrepancies may exist between paa performance and guideline recommendations in individual cases .\nthis is because , for instance , the japanese guideline recommends first - generation or second - generation cephalosporins , penicillins , and aminoglycosides for turp as mentioned above but has not yet established guidelines for holep .\nour most often used paa is sbt / abpc and the duration of dosing is recommended to be within 72 hours .\nhowever , our cases tended to have a longer duration of dosing with a higher ratio of pic occurrence than in other reports , even in preoperative nonpyuria cases .\nour statistical data showed that pic occurrence did not depend on the kind or duration of paa , which suggests that we may be able to shorten the duration of paa , which may lead to the control of unnecessary antibiotic use . regarding causative bacteria , the pic cases included 2 cases of s. marcescens , 1 case of p. mirabilis , and 1 case of k. pneumonia .\nour comparatively broader spectrum paa than recommended in guidelines or other reports , or preoperative intervention against preoperative pyuria cases , might have accounted for this difference .\nthis was a retrospective study and the number of cases was not enough for making definitive conclusions .\nsecond , some of our cases were performed by surgeons who were less experienced with holep and showed a comparatively higher ratio of pic .\nthird , our paa duration of dosing tended to be longer and the kind of antibiotics tended to be broad spectrum , which could lead to the emergence and spread of resistant strains .\nthe results of this retrospective study showed that pic occurrence did not depend on the duration or the kind of paa in our early experience with holep .\nfurther prospective study is necessary for the evaluation and establishment of prophylactic measures for pic .", "answer": "purposethe objective of this study was to retrospectively investigate postoperative infectious complications ( pics ) in our early experience with holmium laser enucleation of the prostate ( holep ) followed by mechanical morcellation for symptomatic benign prostatic hyperplasia.materials and methodsa retrospective review was performed of the clinical data for 90 consecutive patients who underwent holep at our institution between february 2008 and march 2011 . all patients were evaluated for the emergence of pics , including prophylactic antibiotic administration ( paa ) and the influence of the kind or duration of paa on pic . \n the details of cases with pics were also examined.resultsthe patients ' mean age was 71 years ( range , 50 to 95 years ) , and their mean prostate volume was 60 ml ( range , 2 to 250 ml ) . \n there were 7 cases ( 7.78% ) with pics ; in detail , 3 patients were diagnosed with prostatitis , 2 with pyelonephritis , and 2 with epididymitis . \n three patients had positive urine cultures : 1 had serratia marcescens / proteus mirabilis , 1 had s. marcescens , and 1 had klebsiella pneumonia ; only one case had urological sepsis . \n our statistical data showed no significant differences between 2 or fewer days and 3 or more days of paa and pic occurrence . \n there was also no significant effect on pic occurrence of sulbactam / ampicillin compared with other antibiotics.conclusionsthe results of this retrospective study showed that pic occurrence did not depend on the duration or the kind of paa . \n further prospective study is necessary for the evaluation and establishment of prophylactic measures for pics .", "id": 165} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrare fungi have recently been implicated in human infections ranging from colonisation to invasive fungal infections ( ifis ) in immunocompromised patients , accounting for < 10% of all isolated fungal pathogens.1 \n pseudozyma species ( spp . )\nare basidiomycetous yeast classified in the family ustilaginaceae , and its members are close relatives of ustilago maydis and other smut fungi .\ninfections in humans have rarely been reported after the first description as a human pathogen in 2003.3 data regarding the clinical characteristics and pathogenicity in humans remain insufficient .\nrecently , we experienced a case of pseudozyma aphidis fungaemia with invasive fungal pneumonia after reinduction chemotherapy for acute myeloid leukaemia ( aml ) . here , we describe this case and review the global literature .\nmary 's hospital approved this case report and waived the need for patient consent ( no .\na 51yearold man who was diagnosed with aml and had not experienced remission after the first induction chemotherapy started reinduction chemotherapy with 100 mg m cytarabine for 7 days and 90 mg m daunorubicin for 3 days . on day seven after reinduction chemotherapy ( d7 ) , neutropenic fever ( up to 38.0 c ) developed as measured using an axillary thermometer .\nlaboratory data included a white blood cell count of 220 l ( absolute neutrophil count , 0 l ) and creactive protein level of 8.60 mg dl .\nempirical antibiotic therapy with ceftazidime ( 2 g twice a day ) and isepamicin ( 400 mg once a day ) was initiated after performing blood cultures .\non d8 , the results of the blood culture revealed presumptive growth of grampositive cocci ( gpc ) .\nteicoplanin ( 12 mg kg a day after loading with 12 mg kg every 12 h for three doses ) was added based on the culture results .\nalthough the patient had no respiratory symptoms , infiltration was suspected in the right lower lung field on the chest radiograph on d9 .\nlowdose computed tomography of the lung was performed , which showed consolidation with surrounding ground glass opacity at the medial segment of the right middle lobe ( rml ) ( fig .\nthe patient received fluconazole instead of posaconazole as the primary antifungal prophylaxis ; because he had participated in a clinical trial using a thrombopoietin receptor agonist during the same period , a drug interaction was possible .\nthen , the antifungal prophylaxis was empirically changed to caspofungin ( 50 mg a day after the loading dose ) for the possibility of fungal pneumonia according to the revised definition of ifi from the european organization for the research and treatment of cancer / mycoses study group ( eortc / msg).4 \n low dose computed tomography of the lung .\nconsolidation with surrounding ground glass opacity at the medial segment of the right middle lobe .\nthe gpc from the blood culture was identified as vancomycinresistant enterococcus faecium ( 3 of 4 bottles ) , using vitek 2 ( biomrieux , hazelwood , mo , usa ) .\nhowever , the neutropenic fever persisted , and yeastlike organisms were noted from central blood culture ( 1 of 2 bottles ) performed on the same day ( d11 ) .\nthis culture result was reported after 2 days of incubation , using bd bactec fx blood culture system ( bd diagnostics , sparks , md , usa ) .\ncolonies observed on the blood agar plate were white , dry or wrinkled ( fig .\nthe species could not be identified using either vitek 2 or api 20c ( biomrieux ) .\ntherefore , further identification was performed using rdna gene sequencing analysis with the following primers : internally transcribed spacer ( its)1 ( forward primer [ 5tcc gta ggt gaa cct gcg g3 ] and reverse primer [ 5gct gcg ttc atc gat3 ] ) , its2 ( forward primer [ 5gca tcg atg aag aac gca3 ] and reverse primer [ 5tcc tcc gct tat tga tat3 ] ) , and d1/d2 domain ( forward primer [ 5gca tat caa taa gcg gag3 ] and reverse primer [ 5ggt ccg tgt ttc aag acg g3]).5 the isolated gene sequence showed 100% concordance with the p. aphidis strain ( genbank accession number : kf443199.1 and kf443201.1 ) . because the fungaemia developed during the caspofungin therapy and pneumonia was aggravated with persistent neutropenic fever , caspofungin was changed to liposomal amphotericin b ( 5 mg kg per day ) on d15 .\nyeastlike colonies that are dry , creamy , brightly coloured , and glabrous in texture ; ( b ) gram stain showing yeast with branching pseudohyphae ( arrow ) . the followup blood culture performed on\ntransbronchial lung biopsy and bronchial washing and brushing were performed at the rml bronchus to identify the pathogens of fungal pneumonia .\npathology specimens showed inflammatory changes with necrosis and dichotomous hyphae with a septum , suggestive of organising pneumonia with a fungal infection ( fig .\nas the neutropenia recovered , the patient improved clinically and was discharged with itraconazole capsules ( 200 mg twice a day ) . at the outpatient clinic ,\nchest radiography revealed little change in the rml consolidation despite 3 weeks of continued itraconazole .\nconsidering the possibility of both proven invasive pulmonary aspergillosis and fungal pneumonia due to pseudozyma spp .\nthe patient sequentially received consolidation chemotherapy and allogeneic stem cell transplantation ( sct ) while continuing the voriconazole . during the voriconazole treatment , serum level of voriconazole was within the therapeutic range .\nthe pneumonia resolved after 4 months of voriconazole treatment , with complete remission of aml after successful sct .\n( a ) haematoxylin and eosin stain , 100 ; ( b ) haematoxylin and eosin stain , 400 ; ( c ) silver stain , 400 .\ninvasive fungal infections remain a major cause of significant morbidity and mortality in immunocompromised patients , especially those with hematologic malignancies . of the ifis ,\na rare fungus is difficult to treat in the aspects of the early diagnosis and appropriate treatment , which might be related to the severity of the patient 's condition and often challenging intrinsic susceptibility pattern of the pathogens.6 \n pseudozyma spp .\nwas first described as a possible human pathogen in 2003 , when it was identified from blood cultures from three thai patients , as p. antarctica , p. parantarctica , and p. thailandica.3 the first case of p. aphidis human infection was reported in a 7yearold girl with short gut syndrome in 2008.7 \n \n pseudozyma spp .\nis classified under the family ustilaginaceae , phylum basidiomycota , subphylum ustilaginomycotina , class ustilaginomycetes , and order ustilaginales.2 , 8 ustilaginales are plant pathogens that can infect corn plants to produce tumourlike galls . of the pseudozyma spp .\naphidis is known as the most common human pathogen . however , due to the rare isolation of p. aphidis in human infections , this rare fungus species can not be identified using commercial systems that are available in routine diagnostic laboratories . however\n, sequencing and phylogenetic analysis can help with the direct detection of a fungus from blood or tissues because yeast taxonomy is continually evolving .\nwe retrospectively reviewed the global literature to identify the possible risk factors , clinical presentation , and optimal treatment strategies for pseudozyma infection ; in addition to the present case , 14 case reports were found ( table 1).3 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 since 2014 when previous literature review was reported by prakash et al .\ntherefore , we present a updated literature review with some modifications and adding recent cases . of the 15 cases ,\nlevel identification , and the remaining six cases were nonaphidis pseudozyma isolates that were all different spp . from thailand .\nof the nine cases with reported underlying medical conditions , three had gastrointestinal ( gi ) tract problems such as short bowel syndrome or intestinal surgery,4 , 9 , 13 and three had neutropenia7 , 14 , 15 which can damage the gut mucosa .\nof the seven patients for whom the presence or absence of a central venous catheter ( cvc ) was reported , six patients had a cvc .\nthe risk factors are thought to be similar to those of other less common yeast infections including gi tract problems , the presence of a cvc , and neutropenia .\nwe could not identify the exact social history or dietary history to determine potential exposure to plants or crops .\nhowever , crop exposure was identified in two cases : a farmer with mycetoma of the leg and a paediatric patient who had eaten corn chips.8 , 10 in the present case , the possible port of entry for the p. aphidis fungaemia is uncertain .\nwhile the fungaemia met the definition of a catheterrelated bloodstream infection because p. aphidis was isolated only from central blood , the origin of p. aphidis is unclear .\nliterature review of pseudozyma species infections in human amb , amphotericin b ; aml , acute myeloid leukaemia ; cas , caspofungin ; cvc , central venous catheter ; flc , fluconazole ; itc , itraconazole ; lamb , liposomal amphotericin b ; mic , minimal inhibitory concentration ; n / a , not available ; tpn , total parenteral nutrition ; vrc , voriconazole ; 5fc , flucytosine .\nhistopathology of deep tissue from the foot showed grains surrounded by inflammatory cells , periodic acidschiff stain showed clustered yeastlike cells , and tissue cultures showed septate hyaline hyphae on a wet mount .\nthe major manifestation of pseudozyma infection is fungaemia ( 12 of 15 cases , 80% ) ; others ( n = 3 ) have been isolated from a brain abscess that developed after brain surgery , deep biopsy of mycetoma of the leg , and pleural fluid.9 , 10 , 11 in our case , we proved p. aphidis fungaemia with fungal pneumonia from lung tissue .\nhowever , our case has a limitation , in that we could not identify the fungal pathogen from the lung tissue .\nantifungal susceptibility testing was performed in 11 cases of human infections caused by pseudozyma spp .\n, p. aphidis was susceptible to itraconazole , voriconazole , and amphotericin b ; had varying susceptibility to fluconazole ; and was resistant to echinocandines and flucytosine.7 , 8 , 11 , 14 , 15 nonaphidis pseudozyma spp\n. seemed to have susceptibility to amphotericin b only.13 in all reported cases , pseudozyma spp .\n, we described a case of a 51yearold male patient with aml who suffered from neutropenic fever during chemotherapy with a defined bacterial and fungal infection that was finally diagnosed as p. aphidis fungaemia and concurrent invasive fungal pneumonia without genus level identification .\nmany other fungal pathogens show subtle morphological differences between forms found in tissue and in culture\nthis case is worth reporting in the aspect that p. aphidis fungaemia developed during neutropenic fever with concurrent invasive fungal pneumonia in an aml patient .", "answer": "summary \n pseudozyma species rarely cause invasive diseases in humans , which are usually isolated from plants . \n there have been anecdotal reports regarding pseudozyma species infections in patients with underlying diseases or in neonates \n . however , clinical data and the pathogenicity in humans are still insufficient . \n we experienced a case of pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51yearold male with acute myeloid leukaemia ( aml ) . \n p. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rdna gene sequencing analysis . \n the patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the aml and infectious complications . here , we report a case of p. aphidis infection that developed during neutropenia in an aml patient and review the global literature .", "id": 166} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noral hygiene habits are instilled in childhood itself irrespective of the nationality or geographic location of an individual .\nthe most reliable and accepted method of oral hygiene maintenance the world over are mechanical methods of tooth cleaning but adjuvants for decreasing plaque formation and maintaining oral hygiene have been sought .\npresently chemotherapeutic agents are used as adjuvant agents to reduce plaque formation but they have their own disadvantages.1 kavala graha or gandoosha2 are procedures recommended for oral hygiene maintenance in ayurveda .\nit is described as a procedure in which an individual takes a comfortable amount of oil / medicated oil and holds it or swishes it in the mouth .\nwhen the oil turns thin and milky white it is spit out without swallowing.2 dr .\nf. karach popularised this procedure as oil pulling.3 he claimed that oil pulling can cure several illnesses including oral diseases , but his claims were not supported by evidence .\nrecent studies of oil pulling therapy using sunflower oil4 and sesame oil5 were found to decrease plaque induced gingivitis . even though coconut oil is used for gargling among the people in coconut farming communities ,\nno studies have been done on the benefits of oil pulling using coconut oil , to date .\ncoconut oil is an edible oil and is consumed as a part of the staple diet in many tropical countries .\ncoconut oil is different from most other dietary oils because the predominant composition of coconut oil is a medium chain fatty acid , whereas in the majority of other oils the basic building blocks are almost entirely long chain fatty acids .\nhuman breast milk is the only other naturally occurring substance with such a high concentration of lauric acid .\nlauric acid has proven anti - inflammatory effects and antimicrobial effects.678 therefore a study was conducted to assess the effect of coconut oil on plaque formation and plaque related gingivitis .\nthe aim of the study was to evaluate the effect of coconut oil pulling / oil swishing on plaque formation and to evaluate the effect on plaque induced gingivitis .\na total of 60 age matched subjects in the age - group of 16 - 18 years with plaque induced gingivitis were included in the study .\nthe use of systemic or topical antibiotics and the history of dental treatment in the past one month were set as exclusion criteria .\nthe study was designed to compare the baseline values and the post intervention values in a single group performing coconut oil pulling in addition to their oral hygiene routine .\na thorough history regarding the medical condition and the medication taken in the past 6 months was obtained from the subjects .\nall the chosen subjects had a habit of brushing once or twice a day with toothbrush and paste .\nsix subjects had the habit of flossing once in the night along with brushing twice a day .\nthe subjects were advised to routinely perform oil pulling with coconut oil every day in the morning in addition to their oral hygiene routine .\nfive subjects discontinued from the study as they could not tolerate the taste of the oil and three subjects discontinued from the study because of antibiotic usage during the period .\nmodified gingival index9 and plaque index10 were used as the clinical measures to assess gingival inflammation and plaque formation respectively .\nplaque and gingival indices were measured at baseline that is , and on days 1 , 7 , 15 , 30 after the oil pulling routine was started .\nreliability of clinical examination was tested for all the days of assessment and the interexaminer reliability was found to be substantial to good .\nthe kappa coefficient scores were in the range of 65 - 92 [ table 1a and b ] .\nthe mean gingival index was 0.91 and the plaque index was 1.19 at baseline . in comparison to the baseline values both the gingival and the plaque indices substantially reduced during the period of assessment .\nthere was a steady decline in both the plaque index and the gingival index values from day 7 .\nthe average gingival index score on day 30 was down to 0.401 and the plaque index score was 0.385 [ figures 1 and 2 ] .\nstatistical analysis using the paired t test showed that the decrease was statistically significant [ tables 2 and 3 ] .\nkappa scores for modified gingival index kappa scores for plaque index shows the mean and standard deviation of plaque index scores shows the mean and standard deviation of gingival index scores comparison of plaque index scores between baseline , 7 , 15 , and 30 days comparison of gingival index scores between baseline , 15 , 30 and 45 days\ndental plaque is defined clinically as a structured , resilient substance that adheres to intraoral hard surfaces and is composed of bacteria in a matrix of salivary glycoprotein and extracellular polysaccharides .\nplaque induced gingivitis is the result of an interaction between plaque and the tissues and the inflammatory response of the host .\nit is associated with the subtle microbial alterations as the plaque matures.1112 oral hygiene measures using chemo mechanical procedures reduce the incidence of plaque related diseases by decreasing the plaque accumulation .\nour study aimed at checking the effectiveness of oil pulling with coconut oil as an adjuvant to brushing , in decreasing the plaque accumulation and plaque induced gingivitis .\nplaque index by sillness and loe10 and modified gingival index9 were used for clinical assessment in the study as they are the most widely used indices in trials for therapeutic agents.13 oil pulling with sunflower oil was found to significantly reduce plaque index and gingival index after 45 days.4 asokan et al . , found oil pulling therapy with sesame oil was equally effective as chlorhexidine in decreasing plaque induced gingivitis.5 in our study also there was a significant decrease in the plaque and the gingival index at the end of 30 days .\nthere are various hypotheses on the mechanisms by which oil pulling may act in decreasing the plaque and gingival index . in oil pulling , as the oil is swished in the mouth the mechanical shear forces exerted on the oil leads to its emulsification and the surface area of the oil is greatly increased .\nthe oil film thus formed on the surface of the teeth and the gingiva can reduce plaque adhesion and bacterial co aggregation.5 it was also proposed that the alkalis in the saliva can react with the oil leading to saponification and formation of a soap like substance [ figure 3 ] which can reduce the adhesion of plaque.514 coconut oil has a high saponification value and is one of the most commonly used oil in making soaps .\nthe soaps produced with coconut oil can lather well and have an increased cleansing action.15 the lauric acid in the coconut oil can easily react with sodium hydroxide in saliva during oil pulling to form sodium laureate , the main constituent of soap16 which might be responsible for the cleansing action and decreased plaque accumulation .\nsaponification reaction the significant reduction in gingivitis can be attributed to decreased plaque accumulation and the anti - inflammatory , emollient effect of coconut oil . in animal studies\ncoconut oil was found to be an effective burn wound healing agent and this was attributed to its anti - inflammatory and antiseptic properties.17 coconut oil showed moderate anti - inflammatory effects on ethyl phenylpropiolate induced ear edema in rats , and carrageenin and arachidonic acid - induced paw edema.18 it was found be effective and safe when used as an emollient and moisturiser.19 there are many commercially available mouthwashes .\nlisterine ( phenol compound ) and meridol ( an amine / stannous fluoride mouthwash ) were found to be less efficacious than chlorhexidine in controlling plaque induced gingivitis .\nafter 3 weeks of rinsing , plaque indices remained the lowest in the chlorhexidine group , while subjects using listerine or meridol the score were similar but significantly lower than that of individuals rinsing with the placebo solution .\nthe antimicrobial potential of chlorhexidine was found to be the highest followed by meridol.20 in our study there was a 50% decrease in the plaque and gingival index scores in 4 weeks which is comparable to the decrease produced by chlorhexidine .\nchlorhexidine on long term use alters taste sensation and produces brown staining on the teeth which is very difficult to remove .\nthe mucous membranes and the tongue can also be affected and may be related to the precipitation of chromogenic dietary factors on to the teeth and mucous membranes.21 staining is also associated with the of long term use of phenol compound and stannous fluoride containing mouth washes.22 in the present study there were no reported alterations in the taste or noticeable staining from coconut oil at the end of 4 weeks . as an antimicrobial agent , chlorhexidine is effective against both gram positive and gram negative bacteria .\nits antibacterial action is due to an increase in cellular membrane permeability followed by coagulation of the cytoplasmic macromolecules.232425 it has also been shown that chlorhexidine can reduce the adherence of porphyromonas gingivalis to epithelial cells.26 pure - culture studies of 10 oral bacteria ( eight genera ) showed that actinomyces naeslundii , veillonella dispar , prevotella nigrescens , and the streptococci were highly susceptible to chx , while lactobacillus rhamnosus , fusobacterium nucleatum , were less susceptible.27 studies show that coconut oil also has substantial antimicrobial activity .\nit is shown to have significant antimicrobial activity against escherichia vulneris , enterobcater spp . ,\nincluding c. albicans , c. glabrata , c. tropicalis , c. parapsilosis , c. stellatoidea and c. krusei728 studies also show that coconut oil is affective against s. mutans and c. albicans in an in vitro oral biofilm model.29 the antimicrobial potency of coconut oil was not tested in our study .\nfurther studies with a have been planned to check the antimicrobial potential of coconut oil .\nthe fact that a control group with a proven chemotherapeutic agent was not used is the major the limitation of our study .\noil pulling has been proven to be an effective method in reducing plaque formation and plaque induced gingivitis .\nthis preliminary study shows that coconut oil is an easily usable , safe and cost effective agent with minimal side effects which can be used as an adjuvant in oral hygiene maintenance .\nmore studies on the antimicrobial potency of coconut oil on microorganisms causing oral diseases is required to authenticate the use of coconut oil as an effective oral antimicrobial agent .\nfurther studies on coconut oil with a large number of subjects and comparative studies using various chemotherapeutic agents can improve the quality of evidence .", "answer": "background : oil pulling or oil swishing therapy is a traditional procedure in which the practitioners rinse or swish oil in their mouth . \n it is supposed to cure oral and systemic diseases but the evidence is minimal . \n oil pulling with sesame oil and sunflower oil was found to reduce plaque related gingivitis . \n coconut oil is an easily available edible oil . \n it is unique because it contains predominantly medium chain fatty acids of which 45 - 50 percent is lauric acid . \n lauric acid has proven anti inflammatory and antimicrobial effects . \n no studies have been done on the benefits of oil pulling using coconut oil to date . \n so a pilot study was planned to assess the effect of coconut oil pulling on plaque induced gingivitis.materials and methods : the aim of the study was to evaluate the effect of coconut oil pulling / oil swishing on plaque formation and plaque induced gingivitis . \n a prospective interventional study was carried out . \n 60 age matched adolescent boys and girls in the age - group of 16 - 18 years with plaque induced gingivitis were included in the study and oil pulling was included in their oral hygiene routine . \n the study period was 30 days . \n plaque and gingival indices of the subjects were assessed at baseline days 1,7,15 and 30 . \n the data was analyzed using paired t test.results:a statistically significant decrease in the plaque and gingival indices was noticed from day 7 and the scores continued to decrease during the period of study.conclusion:oil pulling using coconut oil could be an effective adjuvant procedure in decreasing plaque formation and plaque induced gingivitis .", "id": 167} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nendoscopic ultrasound ( eus)-guided tissue acquisition is the diagnostic procedure of choice in many diseases of the gastrointestinal tract and adjacent structures .\nthis procedure is well known for its high accuracy and low complication rate ; however , its outcome closely relies on several factors .\nthe location and characteristics of the lesion , endosonographer 's experience , needle size and type , sampling technique , sample preparation , presence of a cytopathologist for rapid on - site examination ( rose ) , and cytologist 's expertise are considered some of the important factors.1,2 issues related to needle selection will be discussed here .\ncurrently , there are three different sizes of commercially available eus fine - needle aspiration ( eus - fna ) needles : 19 , 22 , and 25 gauge ( g ) .\nthe size of the needle should be chosen consciously because it can directly affect the quality of the procured sample . generally speaking ,\nlarger needles may render bigger tissue for diagnosis ; however , samples tend to be bloodier , which might hinder the cytologic interpretation .\nas a 19 g conventional needle is stiff and has limitation in the transduodenal approach , a new flexible 19 g nitinol needle ( expect 19 g flex ; boston scientific , natick , ma , usa ) has been introduced.3 recently , a new side - port needle has been developed by olympus ( tokyo , japan ) , and it is expected to allow better cellular acquisition.4 the spring - loaded 19 g biopsy needle trucut ( cook medical , winston - salem , nc , usa ) has been designed for the procurement of tissue core samples;5 however , it is not feasible to use with the transduodenal approach and has been reported to result in technical failures . the newly developed procore needle ( cook medical ) , which incorporates reverse bevel technology , has various available sizes and enables the transduodenal approach.6\ncurrently , there are three different sizes of commercially available eus fine - needle aspiration ( eus - fna ) needles : 19 , 22 , and 25 gauge ( g ) .\nthe size of the needle should be chosen consciously because it can directly affect the quality of the procured sample . generally speaking ,\nlarger needles may render bigger tissue for diagnosis ; however , samples tend to be bloodier , which might hinder the cytologic interpretation .\nas a 19 g conventional needle is stiff and has limitation in the transduodenal approach , a new flexible 19 g nitinol needle ( expect 19 g flex ; boston scientific , natick , ma , usa ) has been introduced.3 recently , a new side - port needle has been developed by olympus ( tokyo , japan ) , and it is expected to allow better cellular acquisition.4\nthe spring - loaded 19 g biopsy needle trucut ( cook medical , winston - salem , nc , usa ) has been designed for the procurement of tissue core samples;5 however , it is not feasible to use with the transduodenal approach and has been reported to result in technical failures .\nthe newly developed procore needle ( cook medical ) , which incorporates reverse bevel technology , has various available sizes and enables the transduodenal approach.6\nthe advantage of eus - guided tissue acquisition is its high accuracy and safety . according to a meta - analysis ,\nthe pooled diagnostic sensitivity and specificity of eus - fna in the diagnosis of solid pancreatic masses were 86.8% ( 95% confidence interval [ ci ] , 85.5 to 87.9 ) and 95.8% ( 95% ci , 94.6 to 96.7 ) , respectively.7 however , there is no consensus on the number of passes to achieve the highest diagnostic accuracy . increased number of passes may yield a higher diagnostic accuracy with a theoretically higher complication rate .\nthe average numbers of passes to obtain an adequate diagnostic sample for a solid lesion are known to be five to seven passes for the conventional fna needle .\nhowever , the mean number of passes required for diagnosis with the new olympus 22 g side - port needle was only 1.7 in a prospective multicenter study ; however , the number of enrolled cases in that study was small.8 the procore needle seems to be able to obtain enough tissue for diagnosis with only a few passes . when single and multiple ( two to four ) passes of the 25 g procore needle were compared in the diagnosis of solid pancreatic lesions , the sensitivity , specificity , and accuracy were 85% vs. 96% , 100% vs. 100% , and 86% vs. 96% , respectively.9 in a prospective study , the diagnostic accuracy of eus - guided trucut needle core biopsy was 61% , with a mean value of 1.4 needle passes.10 the transduodenal approach was possible only in 40% of the patients . when subgroup analysis was done on technically successful cases only , the diagnostic accuracy was 87.5% . in a multicenter , pooled , cohort study ,\nthe overall diagnostic accuracy of the 19 g procore needle was 85%.6 during transduodenal procedures , sampling was done in 94% ; however , there were some technical difficulties .\nthe combination of eus - fna / fine - needle biopsy ( fnb ) techniques revealed the highest diagnostic accuracy of 91% compared with 77% for eus - fna alone and 73% for eus - fnb alone ( p=0.008).11 another study showed an 84% diagnostic accuracy with eus - guided trucut needle biopsy and suggested the additional use of eus - fna as a rescue diagnostic tool.12 eus - fnb is useful in obtaining core tissue with a few passes\n. rose is critical for the high diagnostic accuracy of eus - fna;13 however , if an endosonographer can obtain visible tissue core with an fnb needle , the outcome may not be dependent on rose , which is not always readily available for many institutions .\naspiration of core tissue with preserved architecture is beneficial for the diagnosis of some specific diseases such as submucosal masses,14 lymphomas,15 and autoimmune pancreatitis.16 as molecular profiling and personalized oncologic therapy are becoming important concepts nowadays , a histologic core biopsy sample is necessary for ancillary testing.17 tissue core can be obtained with a conventional aspiration needle or a specialized fnb needle .\na study reported that satisfactory histologic specimens were procured in 94.7% and tissue acquisition for cytological assessment was successful in 100% , including the transduodenal route , when an expect 19 g flex aspiration needle was used.3 the high tissue acquisition rate is partially because of the high elasticity of the needle , which facilitates the transduodenal pass .\nsmall pancreatic lesions ( < 2 cm ) and nueroendocrine tumors are related to a higher complication rate ; however , no definite relation was proven with patient 's age , location of lesion , needle size , and number of needle passes.18 the type of needle does not seem to pose a big difference in the complication rate .\nmany studies reported that there was no significant difference in diagnostic outcome and needle size .\na study reported that the diagnostic accuracy of the 19 g needle for solid pancreatic and peripancreatic masses was 86.7% and that of the 22 g needle was 78.9% ( p=0.268).19 a 19 g aspiration needle could render a higher amount of tissue ; however , technical failure was more frequent when the mass was located in the head of the pancreas .\nwhen technical failures were excluded , the diagnostic accuracy of the 19 g needle was 94.5% .\nit can be easily bent in a perpendicular direction and also has a wider puncture range .\ntherefore , the 25 g needle is better for targeting pancreatic head and uncinate lesions through the transduodenal route .\nthe obtained sample size may be smaller , but it might result in minimal blood contamination . in a prospective , randomized trial comparing 22 and 25 g needles for solid pancreatic masses , the tissue samples provided positive diagnosis in 87.5% in the 22 g group and 95.5% in the 25 g group ( p=0.18).20 according to a meta - analysis , the pooled sensitivity of the 22 and 25 g needles was 0.85 ( 95% ci , 0.82 to 0.88 ) and 0.93 ( 95% ci , 0.91 to 0.96 ) , respectively .\nthe pooled specificity of the 22 and 25 g needle was 1 ( 95% ci , 0.98 to 1.00 ) and 0.97 ( 95% ci , 0.93 to 0.99 ) , respectively .\nthe 25 g needle showed a higher sensitivity ( p=0.0003 ) but comparable specificity to ( p=0.97 ) the 22 g needle.21 another study showed that the overall accuracy of the 25 and 22 g eus - fna needles and the 19 g trucut needle was 91.7% , 79.7% , and 54.1% , respectively , in the diagnosis of solid pancreatic masses.22 for head and uncinate lesions , the 25 g fna needle was technically more successful and had significantly superior overall diagnostic accuracy than the other needles .\na study compared same - sized fna and fnb needles for the diagnosis of solid pancreatic neoplasms and reported a striking result.23 when five passes of the 22 g echotip ultra needle and two passes of the 22 g echotip procore needle were performed for same lesion alternately for 32 cases , the ability to achieve a diagnosis was 93.8% for fna and 28.1% for fnb . during the fnb procedure ,\nwhen the echoendoscope was positioned within the duodenum , fnb could not be performed because of technical reasons .\nthe authors did not explain the details of tissue processing failures but noted that the \" procore needle failed to obtain enough tissue to survive processing as a regular core biopsy for histology ( tissue attrition during processing ) .\n\" however , a previous randomized trial that compared a 22 g fna needle ( expect ; boston scientific ) and a 22 g fnb needle ( echotip procore ; cook endoscopy , bloomington , in , usa ) for solid pancreatic masses reported different results.24 the diagnostic sufficiency was 100% and 89.3% ( p=0.24 ) for the fna and fnb needle , respectively .\nthe 22 g biopsy needle procured both cytologic and histologic specimen ( 89.3% and 80% , respectively ) , with a 3.6% technical failure rate .\naccording to a meta - analysis , needle size confers only a limited effect on the overall outcomes in eus - fna for solid pancreatic masses.25 a study compared 22 g eus - fna without rose and 19 g trucut biopsy.26 the overall accuracy was 76% for both procedures , whereas the combination of the two procedures rendered a 95% diagnostic accuracy .\nthus , eus - fnb showed a similar diagnostic accuracy to eus - fna without rose , with fewer passes .\nthe authors reported that they can obtain a positive report with eus - fnb when eus - fna was negative in cases of gastrointestinal stromal tumors , pancreatic adenocarcinoma , lung cancer , metastatic mediastinal node , retroperitoneal lymphoma , and mediastinal lymphoma.26\nusually , a cytological sample is enough to establish a diagnosis ; however , histologic assessment may be useful in some cases such as pancreatic tumors other than pancreatic adenocarcinoma , tumors surrounded by chronic pancreatitis , submucosal and intramural gastrointestinal tumors , and for the biopsy of lesions or lymph nodes in which lymphoma is suspected.17 certain diseases such as autoimmune pancreatitis , well - differentiated adenocarcinoma , and highly desmoplastic pancreatic neoplasm may also require tissue core samples for a definitive diagnosis .\nhistological samples can often be obtained with a standard fna needle , and addition of cell block examination can provide good information that is comparable to an fnb sample.27 therefore , eus - fnb can be a recommendable supplementary technique when additional tissue and histologic section are necessary for an accurate diagnosis and if molecular characterization of tumors is required.8,17 the stiffness of the needle is a large obstacle to overcome in harvesting core tissues with the transduodenal approach .\nthe needle size and type can be some of the factors that influence the diagnostic yield of eus - guided tissue acquisition .\nthere are no convincing data showing any significant advantage between the three commonly used fna needle sizes . the smaller 25 g needle , which yields at least comparable results to the 22 and 19 g needles , may be easier to maneuver .\nlarge - bore needles can procure more tissue ; however , the sample tends to be bloodier and technical failure may occur .\nthe yield of an fnb needle is higher with fewer passes and ancillary testing is usually possible .\nneedle selection is a complex process and should be made on the basis of many aspects , such as the location and physical characteristics of the lesion , availability of rose , and clinical needs considering the suspected diagnosis.29", "answer": "endoscopic ultrasound ( eus)-guided tissue acquisition is an indispensable technique for the diagnosis of many diseases of the gastrointestinal tract and adjacent structures . \n eus - guided fine - needle aspiration ( eus - fna ) is known for its high accuracy and low complication rate . however , the outcome of eus - fna highly depends on several factors such as the location and characteristics of the lesion , endosonographer 's experience , technique of sampling and sample preparation , type and size of the needle used , and presence of a cytopathologist for rapid on - site examination . \n eus - guided fine - needle biopsy is useful to obtain core tissue samples with relatively fewer passes . \n aspiration of core tissue with preserved architecture is beneficial for the diagnosis of certain diseases and the performance of ancillary testing such as tumor molecular profiling . \n issues related to needle size , type , and their acquired samples for cytologic and histologic evaluation are discussed here .", "id": 168} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsaudi arabia ( sa ) is a large country with an area of about 2.2 million square kilometers and total population exceeding 27 million , of which 69% are saudis .\nless than one quarter of cancer patients in sa present with localized disease . indeed , most cancer patients present with advanced disease with regional or distant extension .\nthe crude and age standardized cancer incidence rates in 2007 were 52.3 and 82.1 per 100,000 populations , respectively .\nthe five most common cancers , in descending order , are colorectal , non - hodgkin lymphoma , leukemia , lung , and liver in males ; and breast , thyroid , colorectal , non - hodgkin lymphoma , and leukemia in females .\nthe palliative care ( pc ) program at king faisal specialist hospital and research center ( kfshrc ) , riyadh , was established more than 20 years ago as the first program of its kind in the country .\nthe program delivers services for inpatients , outpatients , as well as for those at home through a home health care service .\nthe program has also established a structured postgraduate fellowship for physicians pursuing subspecialty in palliative medicine .\nawareness of symptomatology pattern in cancer patients enables health care professionals to place appropriate emphasis on various challenges in a prioritized manner\n. prioritization process may include patient care plans , professional education plans , and the needs of health care services .\nfurthermore , the quality of life of patients with advanced cancer could be significantly improved if specialized palliative care teams were involved in addressing the variety of symptoms that are common among these patients .\ntherefore , impeccable identification and management of symptoms are two crucial aspects of palliative care . a recent report from 11 european countries\nsuggests that there are variations between countries in the number of inadequately treated cancer - related symptoms . to the best of our knowledge ,\nno previous report has described the prevalence and severity of nonpain symptomatology among patients with advanced cancer in saudi arabia ( sa ) .\nthis paper aims at determining the prevalence and severity of 10 nonpain symptoms in cancer patients visiting the pc outpatient clinic at kfshrc , riyadh , sa .\nthis is a cross - sectional survey exploring the pattern of 10 common nonpain symptoms in an outpatient palliative care clinic .\nthe research advisory council ( rac ) of kfshrc have approved the research project ( rac number 2101053 ) based on the approval of the research ethics committee .\nadult cancer patients who were oriented to person , place , and time were consecutively included in the study .\nthe 10 nonpain symptoms included tiredness , nausea / vomiting , anxiety , depression , shortness of breath , drowsiness , insomnia , dry mouth , loss of appetite , and confusion .\nthe intensity of each symptom at the time of the encounter in the clinic was determined by each patient based on a 010 numerical scoring system where zero means the absence of respective symptom and 10 means the greatest severity a person could possibly imagine .\nthe performance status was determined using the palliative performance scale ( pps ) , which is a reliable and valid observer - rated tool for measuring performance status in pc patients .\nthe pps consists of five domains ( on a scale of 0%100% , with increments of 10% ) , namely ambulation , self - care , activity level / evidence of disease , intake , and conscious level .\nall interviews were conducted by one of the authors ( oa ) to avoid the potential of inter - rater variability .\ndata analysis was conducted using the software package sas version 9.2 ( statistical analysis system , sas institute inc . ,\nthe student 's t test for independent samples was used to compare means between two groups , such as those related to gender , age group , encounter type , and performance status .\none - way analysis of variance was used for comparing the means among more than two groups such as in the case of grouping according to cancer type . a value of p less than 0.05 was considered significant .\na total of 124 patients were interviewed , with a median age of 56 years and dominance of female gender ( 59% ) .\none third of the patients were seen on follow - up basis and the rest were new to the palliative care outpatient clinic .\nall patients had advanced incurable cancer , with the majority ( 102 ; 82.3% ) diagnosed with metastatic disease . for patients who were still receiving anticancer treatment ,\nthe most frequently encountered cancer types were female breast ( 27.4% ) , head and neck ( 15.3% ) , and genitourinary ( 12.9% ) .\nonly one patient denied any nonpain symptom while all other patients had from 1 to 10 nonpain symptoms per patient , with a mean number of symptoms of 5.1 2.2 .\nthe majority of patients ( 93 ; 75% ) had more than 3 nonpain symptoms each .\nthe mean number of symptoms was higher in patients with pps of less than 70% ( 5.9 1.9 ) as compared with those who had better performance status ( 4.6 2.3 ) ( p = 0.002 ) .\nhowever , the mean number of symptoms did not show any statistically significant difference between groups of patients based on age , gender , cancer type , or the type of outpatient encounter .\nthe most frequently reported symptoms were tiredness ( 79.8% ) , loss of appetite ( 71.8% ) , dry mouth ( 69.4% ) , and anxiety ( 60.5% ) , whereas the least prevalent symptoms were nausea and confusion ( 22.6% each ) [ table 2 ] . for symptomatic patients ,\nthe mean severity scores were highest for tiredness ( 5.1 ) and loss of appetite ( 5 ) and lowest for nausea and confusion ( 3.4 each ) as shown in table 2 .\nolder patients ( above the median age , 56 years ) had lower mean anxiety score compared with younger patients , 1.9 and 3.2 , respectively ( p = 0.003 ) .\nfemales had higher mean severity scores than males in 4 symptoms , namely , tiredness ( 4.6 vs 3.5 ; p = 0.04 ) , nausea / vomiting ( 1.0 vs 0.4 ; p = 0.02 ) , anxiety ( 3.2 vs 1.7 ; p = 0.001 ) , and loss of appetite ( 4.2 vs 2.7 ; p = 0.003 ) .\npatients with lower pps tended to have significantly higher severity scores for tiredness , shortness of breath , drowsiness , dry mouth , and loss of appetite , see table 2 .\nthe mean severity scores of symptoms did not significantly differ between patients according to their cancer type or the nature of outpatient visit ( new vs follow - up ) .\nhowever , when patients with primary or secondary lung or pleural disease were pooled in one group , they had higher mean severity scores of shortness of breath compared with other patients , 2.4 and 1.2 , respectively ( p = 0.01 ) . symptom prevalence and severity\nthe participation of all approached patients in our study was not unexpected because the questions were all focused on the presence and severity of symptoms known to be fairly common among cancer patients .\nthe median age of our study population agrees with the findings of a previous report on a larger group of advanced cancer patients in sa and appears generally younger than the median age of the palliative care population in western countries.[911 ] this might be explained by the fact that more than 97% of the saudi population represents those younger than 65 years .\nthe finding that metastatic or locally advanced disease is the rule in the studied population may be explained by the trend of delayed diagnosis of cancer in sa as well as the common practice of delayed referrals to palliative care in kfshrc .\nsymptom prevalence studies on patients with advanced cancer have mostly targeted inpatients rather than outpatients . furthermore , most reports have major variations in demographics of surveyed populations and in methodologies implemented , which obviously make comparisons between the findings of various reports less meaningful .\nthat being said , our findings have shown higher prevalence of nonpain symptoms among patients with advanced cancer compared with what other researchers have reported .\nfor instance , grond and colleagues have reported that cancer patients attending an outpatient pain clinic were having on average 3.3 nonpain symptoms the most prevalent of which were insomnia ( 59% ) and loss of appetite ( 48% ) . according to several reports , it seems that the more symptoms are actively assessed the more symptoms will likely be reported.[1517 ] similar to our results , there is a common finding among various reports that tiredness ( also reported as fatigue or weakness in some studies ) is often on the top of the list of prevalent nonpain symptoms among patients with advanced cancer.[1620 ] potter and coauthors have reported nonpain symptoms in patients seen at an outpatient pc clinic in the uk , with the most prevalent symptoms being tiredness and nausea ( 18% each ) and loss of appetite ( 17% ) .\na recent report from lebanon has shown high prevalence of fatigue ( 88.4% ) , dyspnea ( 65.1% ) , depression ( 53.5% ) , and confusion ( 37.2% ) among inpatients with advanced cancer .\nalshemmari et al . from kuwait have studied cancer patients who were largely having advanced incurable disease and found the most common nonpain symptoms to be fatigue ( 80% ) , anorexia ( 67% ) , weight loss ( 49% ) , and dyspnea ( 42% ) .\noverall , the severity of symptoms reported by our patients was generally more than what has been reported elsewhere on a group of cancer patients hospitalized for palliative reasons .\nour findings have supported previous reports suggesting that poorer performance status may be associated with higher symptom burden .\nin addition , we have found that some symptoms might be associated with higher severity scores in patients with poor performance status .\nhave found , our data failed to show an association between symptom prevalence and age or gender of patients .\nhowever , younger patients in our study had higher severity scores of anxiety than older patients . also , females reported higher severity scores as compared with males in few symptoms including anxiety .\nour finding that patients with primary or secondary lung or pleural cancer were having severe shortness of breath supports what has been suggested by kirkova et al . that some symptoms may vary in prevalence or severity ( or both ) based on cancer site . in the pc outpatient clinic at kfshrc\n, it is common for patients relatives to attend follow - up clinics on behalf of patients for the sake of medication refill , hence the lower proportion of follow - up patients as compared with new patients in our study .\nhowever , one reason could be the fact that many patients reside outside riyadh and , like most saudis , have widely extended families with good chances of having relatives living in riyadh who would be happy to visit the clinic on behalf of the patients .\nalthough air fares for health care - related travel are usually covered by the government , some patients may find it difficult to attend the clinic in person due to poor performance status .\nhowever , we are under the impression that a good number of patients who prefer to send relatives to attend the clinic on their behalf might be having symptoms that are fairly controlled .\nthis could partially explain the high prevalence and severity of symptom burden in our sample as well as the finding that symptom prevalence and severity in our study was similar in patients new to the pc clinic and those returning to the clinic for follow - up .\nlimitations of our study include the relatively small number of participants and the cross - sectional nature of the study design .\na longitudinal design with sequential assessments of a larger group of patients from different centers could have generated more generalizable data .\na much longer list of nonpain symptoms could have been better representatives of symptom burden among this group of patients .\nfuture multicenter research on the same lines may be focused on longitudinally assessing symptom burden in such patients , with emphasis on exploring the efficiency and effectiveness of symptom management strategies in pc outpatient settings .\ndespite the wide variation in reports that explored symptom pattern and prevalence in patients with advanced cancer , it is clear that they all agree upon the fact that patients with advanced cancer are polysymptomatic .\nthe significant prevalence and severity of nonpain symptoms among new and follow - up cancer patients seen in a pc outpatient clinic emphasizes the need for comprehensive assessment and routinely audited symptom management plans .", "answer": "background : epidemiology of cancer - related nonpain symptoms receives less attention in literature as compared with cancer pain.objective:this paper aims at exploring the prevalence and severity of nonpain symptoms in cancer patients attending a palliative care ( pc ) outpatient clinic.materials and methods : over a 5 months period , consecutive adult cancer patients attending pc outpatient clinic at a tertiary hospital were evaluated for the presence and severity of 10 nonpain symptoms . \n patients were grouped to new or follow - up cases and were also grouped according to performance status and cancer type . \n prevalence and severity of symptoms were compared between groups using t test or analysis of variance as appropriate.results:fifty-one males and 73 females were interviewed . \n the most common cancer is female breast ( 27.4% ) followed by head and neck ( 15.3% ) . \n majority of patients ( 67% ) were new to pc clinic . \n patients had 5.1 nonpain symptoms on average , with most common symptoms being tiredness ( 79.8% ) , loss of appetite ( 71.8% ) , dry mouth ( 69.4% ) , anxiety ( 60.5% ) , and depression ( 50.8% ) . \n the least common symptoms were confusion and nausea ( 22.6% each ) . \n the median scores of severity were highest for tiredness , loss of appetite , dry mouth , and insomnia ( 5 points each ) . \n symptoms were fewer among patients with good performance status ( p = 0.002 ) , whereas age , gender , cancer type , and encounter type were not associated with difference in symptom prevalence . \n younger patients , females and those with poor performance status have shown a tendency toward higher severity scores for several symptoms.conclusion:the significant prevalence and severity of nonpain symptoms among new and follow - up cancer patients seen in a pc outpatient clinic emphasizes the need for comprehensive assessment and routinely audited symptom management plans .", "id": 169} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit plays several important physiological and pathological roles in not only reproductive system but also other systems .\nestrogen disorder results in various diseases , such as endometrial diseases , skeletal diseases , and reproductive system tumors .\nincreasing attention has been paid to revealing of the functions of estrogen in physiological and pathological conditions .\nestrogen receptors ( er ) and , the two well established nuclear estrogen receptors , have different physiological functions depending upon their various distributions .\nlots of evidences show that estrogen induces the proliferation of cancer cells in breast , uterus , and ovarian cancer through er. on the contrary , activation of er can reverse this effect .\nnotably , a novel transmembrane estrogen receptor , known as g - couple estrogen receptor ( gper ) , was found .\ner are involved in the initiation , migration , and progression of estrogen - related multiorgan cancers , such as breast cancer , ovarian cancer , prostate cancer , testicular cancer , liver cancer , and lung cancer as well .\nalthough increasing studied are focused on the roles of gper-1 in different types of cancers , the functions of gper-1 in cancers remain unclear yet .\ncharacteristics and functions of reproductive system cancer will be summarized and discussed in the present review .\ng - protein - coupled estrogen receptor-1 ( gper-1 ) , a seven - transmembrane - domain receptor localized in cell surface , was first identified in 1996 .\ngper-1 is detected broadly in numerous human tissues , such as breast , prostate , ovary , placenta , subcutaneous adipose , visceral adipose , arteries , vessels , heart , liver , lung and intestine tissues .\ngper-1 is a member of gpcr superfamily , which is structurally unrelated to the classical er and er. there are four transcriptional variants encoding 375 amino acids composing seven transmembrane proteins .\nbut gper-1 binding domain exists inside the plasma membranes and the endoplasmic reticulum [ 58 ] .\nestradiol , the major type of estrogen , binds to gper-1 with a high affinity to gper-1 while the other two isoforms , estrone and estriol , have very low binding affinities [ 5 , 9 ] .\nfurthermore , numbers of environmental estrogen bind to gper-1 and activate the downstream signaling pathways , such as bisphenol a , genistein , and nonylphenol .\ngper-1-specific compound 1 ( g-1 ) is a specific agonist of gper-1 , which has no function of er and er and was identified using virtual and biomolecular screening in 2006 .\ng-1 has been widely used as a target tool to evaluate the function of gper-1 in different cells and disease models .\ngper-1 mediates both genomic and nongenomic response with its ligands . to date , gper-1 signaling pathways have not been fully elucidated yet .\nthe binding ligands of gper-1 , such as estrogen , g-1 , tamoxifen , and ici182,780 , cross the plasma membrane and bind to the gper-1 on endoplasmic reticulum where they activate its and subunits and subsequently activate both src and adenylyl cyclase ( ac ) leading to the intracellular camp production .\nthe phosphorylation of src induces matrix metalloproteinase ( mmp ) production , which cleaves pro - heparan - bound epidermal growth factor ( pro - hb - egf ) releasing free hb - egf .\nhb - egf binds to the egfr leading to activation of multiple molecules such as ras , pi3k , akt , and erk1/2 .\nthe downstream signal of pi3k and akt results in several nuclear receptors activation which is closely related the proliferation and migration of cancer cell .\ngper-1 also binds to the g - couple protein subunit and activates the phospholipase c ( plc ) , ac , and camp .\nactivated plc results in inositol triphosphate ( ip3 ) production , which further binds to its receptor and leads to intracellular calcium mobilization .\nbreast cancer is generally classified into estrogen receptor positive ( er+ ) and er negative ( er ) . in clinical practices ,\nthe endocrine treatments such as tamoxifen and aromatase are recommended in the er positive breast cancers , while there is no benefit in the er negative cancers .\ngper-1 is widely expressed in both of these breast cancer types and the primary breast cancers .\nrecent clinical study results showed that the expression of gper-1 might correlate with clinical and pathological poor outcome biomarkers .\nother results also showed that the expression of gper-1 was inversely correlated with the er expression .\ncoexpression of gper-1 and er was found in almost 24% patients with inflammatory breast cancer , while 19% only express er and 46% only express gper-1 .\nthe gper-1 mrna levels were significant higher in er positive breast cancer cells compared to er negative cancer cells , and the expression of gper-1 depends on er mrna level .\ninterestingly , gper-1 preformed a different proliferation manner in er positive mcf-7 breast cancer cell line .\ng-1 enhanced migration of mcf-7 breast cancer cells by activating erk1/2 and egfr signaling pathway , which is tremendously attenuated by g15 .\nthe other evidences also approved that gper-1 is an initiator of tamoxifen resistance in breast cancers [ 1921 ] .\nthe promotion roles of gper-1 in cancer cells proliferation and migration may be correlated with the autolysis of calpain 1 , cleavage of cyclin e , or the expression of target gene .\nthere are also some studies which found that gper-1 inhibits the growth of er positive mcf-7 cells , which is probably through g - couple and subunits activating without camp signal activation [ 2124 ] . however , combination treatment with g-1 and her2 antibody trastuzumab exerted an additive growth inhibitory effect on breast cancer cells .\nthus , gper-1 inhibits er positive breast cancers proliferation which is a potential target for er positive breast cancers and drug - resistant breast cancer .\ndeficiency of er in breast cancer is correlated with poor response to endocrine therapy . in er negative breast cancers , gper-1 stimulates the erk1/2 through the egfr / mapk signal cascade , inducing target gene like c - fos expression , which is involved in the progressing of breast malignancies [ 2729 ] .\nestrogen and antiestrogens can also promote the production of the early growth response-1 ( egr-1 ) , connective tissue growth factor ( ctgf ) , and insulin - like growth factor 1 ( igf-1 ) through the gper-1 [ 28 , 30 , 31 ] .\ngrp30 activation stimulated breast cancer cells migration through ctgh , cxc receptor ( cxcr1 ) , and notch pathways . furthermore , gper-1 agonist g-1 promoted inflammation in breast cancers .\ngper-1 was reported to affect the deformation of breast glandular structure inducing the malignant transformation of breast tissue .\ngper-1 can also induce expression of cancer - associated fibroblasts ( cafs ) in tumor microenvironment [ 34 , 35 ] . on the contrary\n, a recent study showed that activation of gper-1 by g-1 resulted in g2/m - phase arrest and induction of mitochondrial - related apoptosis .\nthe other studies also proved that g-1 treatment suppressed the growth of skbr3 cancer cells and increased the survival rate by inducing the erk1/2 signal activation [ 36 , 37 ] .\n1520% of breast cancers are included in triple negative breast cancers ( tnbc ) , characterized by lack of er , progesterone receptor ( pr ) , and egfr2 ( her-2 )\n. a higher rate of recurrence and aggressive biological features were found in younger females [ 38 , 39 ] .\ngper-1 expression was found in majority of tnbcs patients . in the gper knockdown mice model , the proliferation of tnbcs ,\nthese findings suggest that gper plays a key role in putative mechanism for tnbcs and gper might be a therapeutic target for tnbcs .\nsnps of gper-1 , histone acetylation , and transcription factor recruitment were significantly associated with tumor size and histological grading [ 42 , 43 ] .\ngper rna as well as gper-1 protein presents in both primary and malignant ovarian tumor tissues . the expression of gper-1 was significantly increased in ovarian carcinomas compared to pericarcinomatous tissues impendent with the expression of egfr , er , and er .\nestrogen and g-1 induce ovarian cancer cell growth responses via egfr - mapk signaling pathways .\nfurthermore , gper-1 promoted the migration and invasion of ovarian cancer cells ovcar5 which is characterized by negative er and positive gper by increasing the expression mmp-9 [ 48 , 49 ] .\natrazine , one of the most common pesticide contaminants , promoted ovarian cancer cells proliferation via induction of erk and expression of estrogen target gene through gper-1 pathway .\nbut other studies results showed that g-1 suppressed proliferation and induced apoptosis of human ovarian cancer cells probably through inhibition of cell cycle progression in g2/m - phase in ovarian carcinomas [ 51 , 52 ] . \n\ngper-1 has been shown to be involved in a variety of hormone - dependent cancers .\nit is well understood that estrogens play a critical role in pathological germ cell proliferation in testicular germ cell tumors .\ngper-1 seems to be involved in modulating the growth of estrogen dependent testicular cancer cells .\nestrogen induces the high expression of gper-1 correlated with low levels of er in human testicular carcinoma in situ and seminomas [ 53 , 54 ] .\nbisphenol a , a common environmental estrogen , can also promote the proliferation of testicular seminomas cells through gper-1 .\nthe above findings suggested that gper-1 may be a potential therapeutic target [ 56 , 57 ] .\nestrogen has an efficacy for advanced prostate cancer ( pc ) via the mediation of the classical estrogen receptors .\nthe effects of er on pc growth and metastases have different mechanisms in different cellular microenvironments .\nthe expression of gper-1 is higher in the preneoplastic lesions and normal areas of benign prostate than the basal epithelial cells .\ng-1 , the selectively activating gper-1 , inhibited the growth of multiple pc cells in vitro and in vivo through erk1/2 and c - jun / c - fos signaling pathways , which indicates that the g-1 may be a new option for pc through targeting gper-1 .\ng-1 inhibited castration - resistant phase but had no effect on androgen - sensitive tumors .\nthe antitumor effect of g-1 on cr tumors was related to necrosis ( approximately 65% ) accompanied with neutrophils infiltration .\ng-1 can also upregulate neutrophil - related chemokines and inflammation - mediated cytokines in the cr tumors . in one word\nthere are other studies which proved that gper-1 induced proliferation , differentiation , and drug resistance of lung cancers [ 63 , 64 ] , thyroid cancers , bladder cancers , and oral squamous carcinomas .\nmore studies to reveal the functions and mechanisms of gper-1 in the other system cancers are warranted .\nmajority of the study results addressed that activation of gper-1 by estrogen and g-1 results in the downstream signals and target genes activation , which promotes the proliferation , migration , and invasion of cancer cells . and\nthis effect is in nonclassical er expression dependent manner in most cancers except for ovarian cancers .\nit is interesting that several other studies showed that g-1 , the special agonist of gper-1 , promoted the expression of gper-1 and inhibited the proliferation of er negative breast cancer cells , ovarian cancer cells , and prostate cancer cells .\nthe opposite effects of gper-1 in cancer cells may be associated with the epigenetic of gper-1 , such as the snps and histone acetylation .\nthe different cell types , tumor microenvironment , and hormonal level may also affect the functions of gper-1\n. controversies still exist on the gper-1 localization and related signaling pathways , in particular the potential action as proapoptotic mediator . since the function and mechanisms of gper-1 are still unclear , more researches and clinical studies are strongly warranted to clarify the different function and mechanisms in different cancer types and conditions .", "answer": "the g - protein - coupled estrogen receptor-1 ( gper-1 ) , also known as gpr30 , is a novel estrogen receptor mediating estrogen receptor signaling in multiple cell types . \n the progress of estrogen - related cancer is promoted by gper-1 activation through mitogen - activated protein kinases ( mapk ) , phosphoinositide 3-kinase ( pi3k ) , and phospholipase c ( plc ) signaling pathways . however , \n this promoting effect of gper-1 is nonclassic estrogen receptor ( er ) dependent manner . \n in addition , clinical evidences revealed that gper-1 is associated with estrogen resistance in estrogen - related cancer patients . \n these give a hint that gper-1 may be a novel therapeutic target for the estrogen - related cancers . \n however , preclinical studies also found that gper-1 activation of its special agonist g-1 inhibits cancer cell proliferation . \n this review aims to summarize the characteristics and complex functions of gper-1 in cancers .", "id": 170} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneurofibromatosis type-1 ( nf-1 ) is a multisystem , autosomal dominant disorder of peripheral nerves affecting nearly 1/3000 individuals worldwide.1 it was first described by a german pathologist , friedrich daniel von recklinghausen .\ninherited or spontaneous mutation of the neurofibromin gene located on chromosome 17 is responsible for this diverse disorder .\ncommon skeletal manifestations of nf-1 include spinal deformities , congenital tibial dysplasia ( congenital bowing and pseudarthrosis ) , sphenoidal dysplasia and cystic lesions in bones . pathological fracture of the acetabulum with anterior dislocation of hip secondary to osseous involvement of the acetabulum , femoral head , and pubic rami has never been documented in a case of nf-1 .\na 16-year - old boy presented with the complaints of pain in the left hip associated with the inability to bear weight following a trivial fall . on examination , the affected limb was 1.5 cm short , abducted and externally rotated .\non general examination , patient had 8 caf au lait spots over the body , bilateral axillary freckles and multiple palpable neurofibromas in the subcutaneous tissues of forearm , thighs and back [ figure 1 ] .\npatient met three out of seven criteria described for the diagnosis of nf-1 [ table 1].2 plain radiograph and computed tomography scan of pelvis revealed an ill - defined lytic lesion causing pathological fracture - dislocation of the left hip [ figure 2 ] .\nmagnetic resonance imaging ( mri ) showed additional soft tissue involvement and joint effusion [ figure 3 ] .\nultrasound guided fine - needle aspiration cytology showed scanty cellularity with round to oval cells having minimal pleomorphism ; hyperchromatic nucleus and moderate cytoplasm with spindle cells and osteoblasts .\nclinical photograph showing skin lesions - caf au lait spots ( black arrows ) and axillary freckling ( white arrow ) criteria for diagnosis of nf-1 ( at least 2 or more features ) preoperative radiograph anteroposterior view ( a ) and computed tomography scan ( b ) of pelvis showing an ill - defined lytic lesion destroying anterior column of acetabulum , pubic rami and part of the femoral head coronal ( a ) and axial ( b ) sections of magnetic resonance imaging of pelvis showing expansile lytic lesion of acetabulum and pubic rami with soft tissue involvement and joint effusion a wide local excision followed by arthrodesis of the joint was planned .\nconsidering the extent of bony and soft tissue involvement , we used a modification of the ilioinguinal and iliofemoral approach to have a wide exposure .\nwe used the conventional ilioinguinal incision and combined it with femoral part of the iliofemoral incision [ figure 4a ] .\non exposing the pelvis , anatomy was distorted . the deformed femur head and acetabulum with deficient pubic rami\nthere was extensive soft tissue involvement adjacent to the acetabulum and lower part of the ilium .\nthe entire acetabulum with 2 - 3 cm clear margin of the ilium was resected along with the abnormal soft tissue .\niliofemoral arthrodesis was done using a 14 hole stainless steel dynamic compression plate [ figures 4c d , and 5 ] .\nintraoperative photographs showing ( a ) skin incision ( b ) deformed femoral head ( c ) 14 hole dcp ( d ) iliofemoral arthrodesis postoperative radiograph after tumor resection and iliofemoral arthrodesis histopathology revealed dense collagenous tissue cores with spindle cells having blunt nuclei with minimal atypia and no mitosis or necrosis [ figure 6a ] . on immunohistochemistry , cells were s-100 positive and of neural origin [ figure 6b ] .\npartial weight bearing was allowed at 6 weeks and full weight bearing at 10 weeks . at 1-year followup ,\nthe patient was comfortable , pain free , able to ambulate unassisted , stand on one limb , sit and climb stairs without any difficulty [ figure 7 ] .\n( a ) histopathological photomicrograph showing dense collagenous tissue cores and spindle cells with blunt nuclei .\n( b ) immunohistochemistry showing neural marker s-100 positivity clinical photographs showing functional outcome at 1-year followup\ntype 1 neurofibromatosis or von recklinghausen disease , is a multisystem disorder that primarily affects the cell growth of neural tissue and characterized by involvement of skin , peripheral nerves , subcutaneous tissue , eyes , and skeletal system .\nalthough involvement of the musculoskeletal system is common , there have been only a few cases of subluxation / dislocation of hip in patients with nf [ table 3].34567891011121314 on reviewing the literature , the etiology of hip instability leading to pathological subluxation / dislocation in patients with nf-1 can be classified as local and remote .\nmost of the cases are secondary to local ( intra and peri - articular ) neurofibromas , which can result in mass effect , bony erosions ( ilium , acetabulum , and femoral neck ) , acetabular dysplasia , narrowing of the femoral neck , coxa valga , increased femoral neck offset , capsuloligamentous laxity , and synovial membrane proliferation.3458101113 remote causes of hip instability include intra spinal neurofibromas / schwannomas leading to motor deficit ( hip abductor weakness ) or sensory deficit ( charcot 's neuropathic arthropathy ) , limb length discrepancies secondary to hemi - hypertrophy of lower limb and abnormal biomechanical alteration in the spinopelvic alignment due to scoliosis.6791011 endo et al . described anterior subluxation of hip secondary to decreased femoral head coverage resulting from decreased lumbosacral lordosis and posterior pelvic inclination following scoliosis correction.11 until date , there has been no case of nf-1 reported in the literature with pathological fracture of the acetabulum with anterior dislocation of hip attributable to a neurofibroma involving the acetabulum , pubic rami and femoral head .\northopedic manifestations of nf-1 comprehensive literature review on published cases of hip dislocation / subluxation in nf-1 the various treatment options described for pathological hip dislocations in nf-1 include closed reduction , open reduction , shelf operation with fascia lata tenorraphy , rotational acetabular osteotomy with femoral varus osteotomy , girdle stone resection , total hip replacement with the trochanteric distalisation.791114 the rate of re dislocation is very high in most of the cases , subsequently requiring a secondary surgical procedure for stabilization . since only a handful of cases have been described in the literature , it is difficult to comment upon the best line of management . in our case ,\narthrodesis was the best possible option since the bone stock after tumor resection was so inadequate that none of the above mentioned procedures could be tried .\nmoreover , the fear of redislocation , which might necessitate repeated surgeries , was negated .\na combination of ilioinguinal and iliofemoral approach was employed to have a better exposure of the hip joint .\nthe neurofibromatous tumors associated with nf-1 are usually benign ; however , there is a 2 - 5% chance of malignant transformation , especially with plexiform neurofibromas.15 plexiform neurofibromas are diffuse , poorly defined nerve sheath tumors arising from multiple nerve fascicles and surrounding tissues .\nthey are more prone for hemorrhage , dysfunction , pain , disfigurement , and malignant transformation.16 there was no clinical or radiological evidence of recurrence or malignant transformation in our patient at 1-year followup .\nsubtle clinical signs such as skin patches , axillary freckling , and subcutaneous neurofibromas can be easily missed .\northopedic surgeons must be aware about the various management options available and tailor them as per the needs of their patient .\niliofemoral arthrodesis offered a good functional outcome with improved quality of life in our case .", "answer": "skeletal neurofibromatosis ( nf ) commonly manifests as scoliosis and tibial dysplasias . \n nf affecting the pelvic girdle is extremely rare . \n pathological fracture of the acetabulum leading to anterior hip dislocation in a patient with nf-1 has never been reported in the literature . \n the paper presents the clinical symptomatology , the course of management and the successful outcome of such a rare case of nf-1 . \n histopathological and immunohistochemistry studies showing abundant spindle cells , which are s-100 positive and of neural origin are the classical hallmarks of neurofibromatous lesions . \n tumor resection and iliofemoral arthrodesis can be considered as a valid option in young patients with pathological fracture dislocation of the acetabulum .", "id": 171} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbacteria of the genus actinomyces are gram - positive bacilli which generally colonize mouth , colon and vagina .\n, if actinomycosis occurs , it often presents as an indolent , slowly progressive infection characterized by abscess formation , which can progress across tissue boundaries , can present with mass like features which simulate malignancy , can develop into a sinus tract and/or develop clinically into a refractory or relapsing infection after a short course of therapy .\na 43-year old woman with no significant medical history presented with complaints of an unilateral slowly growing painful mass in the left breast .\nmammography ( fig . 1 ) and ultrasonography were conducted and showed a small abscess - like density retroareolarly.fig .\n. 1 mammography of the left breast showing a confined density in the retroareolar area .\nspecies identification was performed using matrix - assisted laser desorption ionization - time - of - flight mass spectrometry ( maldi - tof ms ; bruker ) .\nsusceptibility testing for a. neuii was performed using e - tests ( biomerieux ) . at the time that culture findings became available ,\ntherefore , the cultured actinomyces was considered as skin commensals and a wait and see policy was installed .\nafter several months , the patient returned to the outward clinic with complaints of pain in the breast .\npsychical examination of the breast showed mild erythema and ultrasonography showed a minimal increase of the lesion .\nthe abscess was surgically drained and new purulent fluid from the abscess was sent to the laboratory . the material was processed as described above .\nin contrast to initial culture findings , determination by the maldi - tof ms showed peptostreptococcus magnus ( score value 2.056 ) . after four days there was also growth observed in the brewer thioglycollate medium .\nthe isolate was shown to be susceptible to penicillin , amoxicillin , clindamycin , meropenem and vancomycin .\nhistopathological examination of the obtained tissue showed abscess formation in an infection with a sinus tract .\nsubsequently , the patient was treated for six weeks of intravenous penicillin followed by six months of oral amoxicillin successfully .\nsecondly , a 73-year old woman with a history of bilateral breast cancer was seen at with severe pain and swelling of the left breast ten days after her ablation which was complicated by a large hamatoma treated conservatively .\ngram strain showed many leukocytes , some gram - positive cocci and many gram - positive rods .\ndetermination using maldi - tof ms identified a staphylococcus aureus after 2 days there were colonies visible on the anaerobically incubated schaedler agar .\ndetermination by the maldi - tof ms revealed an a. neuii susceptibility testing was performed using e - tests .\nunfortunately , patient returned four days after discharge with a relapse of the hematoma which was surgically evacuated . a month later at the outward clinic she showed full recovery.fig .\nother isolates that have been identified as pathogens causing primary breast actinomycosis include actinomyces viscosus , actinomyces turincensis and actinomyces radingae \n .\nit differs from the other actinomyces species because of its aerobic growth and its microscopic morphology without branching .\nwe were able to retrieve only three former cases of a. neuii causing primary actinomycosis .\nin the first case , treatment with antibacterials was unsuccessful and the lesion had to be surgically removed . in the second case ,\npatient was successfully treated with amoxicillin for 21 days . in the third case ,\nactinomycosis , regardless of species , should be treated with high doses of antibacterials for a prolonged period of time although therapy needs to be individualized .\ncurrent guidelines recommend high dose of penicillin intravenously for two to six weeks , followed by oral therapy with penicillin or amoxicillin for 6 to 12 months .\nalternative antibacterial treatments include doxycycline , erythromycin or clindamycin . if actinomycosis presents with well - defined abscess then surgical drainage followed by long - term antibacterial therapy is indicated .\nwe describe this combination of treatment in our cases . in the first case initial cultures showed islolated a. neuii . because signs of infection had decreased this finding was interpreted as skin flora and not as a pathogen . therefore medical treatment was considered unnecessary .\nin retrospect , if antibacterial therapy had been given at first presentation recurrence of the infection might have been prevented .\nactinomyces species morphologically resemble diphtheroids and could be dismissed as skin commensals , even when isolated from an abscess sample . in both of our presented cases we found different organisms in the culture additional to a. neuii . in\nthe first case we found p. magnus and in the second case s. aureus was present .\nalthough a. neuii infection is known for its chronicity , the influence of these mixed organisms on the severity of infections remains unclear .\nfurther research on the effect of mixed organism on the severity of an a. neuii infection is required .", "answer": "actinomycosis is a slowly progressive infection caused by anaerobic bacteria , primarily from the genus actinomyces . \n primary actinomycosis of the breast is rare and presents as a mass like density which can mimic malignancy . \n mammography , ultrasonography and histopathologic examination is required for diagnosis . \n treatment should consist of high doses of antibacterials for a prolonged period of time and possibly surgical drainage . \n primary actinomycosis infections are commonly caused by a. israelii . \n actinomyces neuii is a less common cause of classical actinomycosis . \n we present two cases of primary actinomycosis of the breast in two female patients caused by a. neuii .", "id": 172} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nstarvation and other altered metabolic conditions such as immobilization , denervation , \n aging , and unloading states induces loss of muscle mass1,2,3,4 . to study the signal \n transduction of atrophy in particular ,\nvarious cell culture models have been developed5,6,7 . in many studies , exogenous cytokines such \n as tnf-\n, glucocorticoids such as dexamethasone , and serum - free starvation of cultured cells \n have been used as atrophy models to confirm the mechanisms of whole skeletal muscle atrophy \n in vivo8,9,10 .\nthe elevated degradation of proteins in \n skeletal muscle atrophy and serum - free starvation is commonly coupled with activation of the \n protein ligases such as muscle specific ring finger-1 ( murf-1 ) and atrogin-11 , 4 , 5 , 11\n. \n meanwhile , cofilin is a ubiquitously expressed protein in mammalian cells and thereby \n regulates the actin filament dynamics and reorganization and other functions12,13,14 .\nfurthermore , cofilin binds to actin \n molecules , changing fibrous actin to globular actin13 .\nthis process is enabled by the dephosphorylation of cofilin by \n phosphatases12 , 15 . on the other hand , phosphorylation of cofilin\nabolishes the \n cofilin activity and inhibits its severing function12 , 16 ( fig . 1cfig .\n1.change in phosphorylation of protein and schematic representation of the cellular \n response caused by serum - free starvation with low glucose .\nmorphologic ( a - a30 , \n a - b100 ) and immunoblotting ( b ) analyses in the starved l6 myoblasts .\nfbs , fetal \n bovine serum ; h , hours ; e. period , experimental period ; hg , high - concentration \n glucose ; lg , low - concentration glucose ; p - cofilin , phosphorylated cofilin ; r , \n receptor ; f - actin , fibrous actin ; g - actin , globular actin ; rho - rac - cdc42 , rho family \n small gtpases ; rock , rho - associated protein kinase ; pak , p21-activated protein kinase ; \n ssh , cofilin - specific phosphatases slingshot ; skeletal mcs , skeletal muscle cells . ) .\nhowever , the changes in phosphorylation of cofilin in starvation - induced atrophy \n are not fully understood .\ntherefore , we investigated the changes in the phosphorylation of \n cofilin in l6 myoblasts during serum - free starvation with low glucose\n. change in phosphorylation of protein and schematic representation of the cellular \n response caused by serum - free starvation with low glucose .\nmorphologic ( a - a30 , \n a - b100 ) and immunoblotting ( b ) analyses in the starved l6 myoblasts .\nfbs , fetal \n bovine serum ; h , hours ; e. period , experimental period ; hg , high - concentration \n glucose ; lg , low - concentration glucose ; p - cofilin , phosphorylated cofilin ; r , \n receptor ; f - actin , fibrous actin ; g - actin , globular actin ; rho - rac - cdc42 , rho family \n small gtpases ; rock , rho - associated protein kinase ; pak , p21-activated protein kinase ; \n ssh , cofilin - specific phosphatases slingshot ; skeletal mcs , skeletal muscle cells .\nl6 myoblasts from rat neonate skeletal muscle were separated into control and serum - free \n starvation groups1 .\nthe control group of \n l6 myoblasts was purchased from the american type culture collection ( rockville , md , usa ) \n and cultured in dulbecco s modified eagle s medium containing 10% fetal bovine serum , 100 \n u / ml penicillin , 100 g / ml streptomycin , 200 mm glutamine , and 4,500 mg / l high - concentration \n d - glucose .\nthe serum - free starvation group of l6 myoblasts grown to 6070% confluence and \n undernourished in dmem containing 1,000 mg / l low - concentration d - glucose without fbs for 3 , \n 6 , 12 , 24 , 48 , and 72 h , respectively1 . \n\nafter each experimental treatment , cells were lysed with an extraction buffer ( 20 mm hepes , \n ph 7.5 , 1% nonidet p-40 , 150 mm nacl , 10% glycerol , 10 mm naf , 1 mm \n na3vo4 , 2.5 mm 4-nitrophenylphosphate , 0.5 mm pmsf , and one tablet \n of complete proteinase inhibitor cocktail [ roche , indianapolis , in , usa ] ) .\nthe morphological \n changes in l6 myoblasts with or without each experimental treatment were visualized with an \n inverted microscope ( ae30/31 , motic incorporation , richmond , bc , canada ) . to measure the \n phosphorylation of cofilin\nproteins ( 3045 g / lane ) were \n separated on 12% polyacrylamide sodium dodecyl sulfate gels and then transferred \n electrophoretically to a polyvinylidene fluoride membrane ( millipore ; bedford , ma , usa)2 .\nanti - cofilin antibody was purchased from \n santa cruz biotechnology ( santa cruz , ca , usa ) .\nantibody - specific bands were quantified \n using an image analyzer ( bio - rad ) .\nthe protocol for the study was approved by the committee \n of ethics in research of the university of yongin , in accordance with the terms of \n resolution 5 - 1 - 20 , december 2006 .\nthe data were \n statistically evaluated using student s t - tests for comparisons between pairs of groups and \n by anova for multiple comparisons . a p value of < 0.05 was considered to be statistically \n significant .\nl6 cell sizes and numbers were diminished as a result of serum - free starvation in a \n time - dependent manner ( fig .\nphosphorylation \n of cofilin was significantly decreased after 3 , 6 , 12 , 24 , 48 , and 72 hours of starvation \n compared with those of the control groups ( n=34 , fig . \n 1b , table 1table 1.changes in expression and phosphorylation of cofilin of l6 myoblasts during \n serum - free starvation with low glucoseexperimental periodcofilin ( % ) p - cofilin ( % ) 0 hour ( control)100.00.0100.00.03 hours252.329.5 * 20.76.1 * 6 hours242.720.7 * 25.34.6 * 12 hours201.026.2 * 24.76.3 * 24 hours198.722.9 * 26.35.9\n* 48 hours196.022.1 * 24.35.4 * 72 hours176.314.4 * 18.05.5*data were presented as the mean sem .\nthe basal levels of \n abundance and phosphorylation in controls ( 0 hour ) were considered to be 100% . \n * compared with the 0 hour control , p<0.05 . ) .\nhowever , the expression of cofilin was significantly increased after 3 , 6 , \n 12 , 24 , 48 , and 72 hours of starvation compared with the expression of cofilin in the \n control groups ( n=34 , fig .\np , phosphorylated protein . the basal levels of \n abundance and phosphorylation in controls ( 0 hour ) were considered to be 100% . \n * compared with the 0 hour control , p<0.05 .\nskeletal muscle atrophy and joint contracture have proven to be significant orthopaedic \n problems in the area of physical therapy3 , 17 , 18 .\nthe skeletal muscle is the largest organ with high plasticity in the \n human , comprising about 50% of the total body weight .\nmaintenance of muscle mass and \n neuromuscular function is important for activities daily living ( adl ) in patients1 , 2 , 19 , and maintenance of muscle mass in \n particular is related in part to optimal nutrient absorption and use . in contrast , nutrient \n starvation and disuse have in part the potential to negatively impact muscle mass such as \n through skeletal muscle atrophy20,21,22,23 .\nour previous study reported that the \n ubiquitin protein ligases murf-11 and \n atrogin-1 ( data not shown ) , markers of muscle atrophy , are increased in atrophied \n gastrocnemius muscle strips and involved in the development of serum - free starvation - induced \n atrophy in l6 myoblasts . simultaneously , extracellular signal - regulated kinase 1/2 ( erk1/2 ) , \n stress - activated protein kinase / c - jun nh2-terminal kinase \n ( sapk / jnk ) , and p38 mitogen - activated protein kinase ( p38mapk ) are involved in atrophy \n caused by cast immobilization of a hind limb and serum - free starvation of l6 myoblasts1 , 2 . \n\nalso , our previous report demonstrated that cast immobilization of rat gastrocnemius muscles \n increases the expression of tissue myoglobin24 .\nmeanwhile , cofilin in eukaryotic cells binds to actin and plays a \n role in actin dynamics and reorganization involved in cast immobilization - induced \n atrophy14 , 25 .\nphosphorylation of cofilin is achieved by lim kinases and thereby \n inhibits the actin binding , severing , and depolymerizing activities of cofilin16 , 25 \n ( fig .\nfurthermore , the kinases responsible \n for this phosphorylation are rho - associated protein kinase and p21-activated protein kinase , \n which are downstream kinases of the rho family small gtpases26,27,28 . on the other hand , dephosphorylation of cofilin\nis mediated by the \n cofilin - specific phosphatases slingshot12 , 15 ( fig . \n\nalthough cofilin is essential for maintenance of skeletal muscle mass12 , it has not been reported that \n phosphorylation of cofilin is related to atrophy caused by serum - free starvation in the area \n of physical therapy . however , further systematic studies in the area of physical therapy \n such as electrotherapy , neurotherapy , hydrotherapy , and others are needed to confirm the \n mechanism of cofilin under atrophic conditions29,30,31 ( fig .\nin summary , \n the phosphorylation of cofilin was decreased in starved skeletal muscle cells .\nthe present \n results suggest that serum - free starvation - induced atrophy may be in part mediated by \n cofilin from l6 myoblasts .", "answer": "[ purpose ] many studies have been using cell culture models of muscle cells with exogenous \n cytokines or glucocorticoids to mimic atrophy in in vivo and in vitro tests . \n however , the \n changes in the phosphorylation of atrophy - related cofilin are still poorly understood in \n starved skeletal muscle cells . in this study \n , we first examined whether or not \n phosphorylation of cofilin is altered in l6 myoblasts after 3 , 6 , 12 , 24 , 48 , and 72 hours \n of serum - free starvation with low glucose . [ methods ] we used western blotting to exam \n protein expression and phosphorylation in atrophied l6 myoblasts . \n [ results ] l6 cell sizes \n and numbers were diminished as a result of serum - free starvation in a time - dependent \n manner . \n serum - free starvation for 3 , 6 , 12 , 24 , 48 , and 72 hours significantly decreased \n the phosphorylation of cofilin , respectively . \n [ conclusion ] these results suggest that \n starvation - induced atrophy may be in part related to changes in the phosphorylation of \n cofilin in l6 myoblasts .", "id": 173} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe truth is that most medical breakthroughs have ultimately come from basic research , and i think that we as scientists need to do a better job of telling these success stories .\nmy favorite example is that antibiotics came out of finding a random contaminant on a plate . and remember that we have crispr [ clustered regularly interspaced short palindromic repeats ] tools only because people were studying some bizarro antipathogen mechanism in bacteria .\nit s a beautiful example of something entirely unanticipated coming out of left field . that s why it s important to maintain funding for a very diverse program of basic research ; history tells us you ca nt predict where the next advance will come from .\nright now it seems like funding agencies and the public have an engineering mentality , and they believe that , as long as we think hard enough about a problem , we can solve it .\nthat s an admirable attitude , but in the life sciences it s not always the right path to discovery .\ni would argue that under some circumstances , studying yeast cells is a better idea than studying highly transformed human cells in a dish .\nfor many years , we used to write in the significance section of grant applications that the reason that it is important to understand chromosome segregation is because , when it fails , cells become aneuploid and cancerous .\nwhy should aneuploidy cause cells to proliferate ? when you do yeast crosses and by chance get an aneuploid strain , invariably the cells do poorly . and\none explanation is that building an organism is a complicated procedure , so if you change the gene dosage of certain genes , you mess everything up . that s probably true\nyou could then further argue that , at the cellular level , maybe it does nt really matter how many chromosomes you have , as long as you have at least one of each .\nperhaps extra chromosomes are actually good for an individual cell and allow it to keep proliferating when they should not and this gives you cancer .\nhowever , we never thought this was very likely , given that aneuploid yeast often proliferate poorly .\nyou can very agnostically ask : what happens to a cell if you change the chromosome number ?\nyeast was the right organism for this because we have genetic tricks and selection methods to generate aneuploids that are stable enough to study .\nbecause this allowed us to examine many different types of aneuploidies at the same time , we could look for broad patterns\n. we could nt have done it in any other organism . actually , we do all our discovery work in yeast . and when we find something interesting , we move it into the mouse or human cell lines and ask whether we see the same thing .\nsometimes the answer is no , but more often the answer is yes .\n it s just harder to discover fundamentally new things in very complex organisms where the repertoire of tools is limited .\nand i would argue that , under some circumstances , studying yeast cells is a better idea than studying highly transformed human cells in a dish .\nangelika amon s work over the past 15 years has guided all of us who think about mitotic and meiotic cell division .\n, we wondered whether there was a systematic way the cell avoids losing or gaining chromosomes . to be honest\n, i was hoping there would be some kind of cute mechanism that counts chromosomes . that turned out to be completely wrong . or at least we havent been able to find anything of this sort .\nonce we realized that , we had to step back and let the genetics lead the way .\nwe did a lot of phenotypic characterization and then developed hypotheses to explain the patterns we saw .\nif complex subunits are not expressed in the correct ratios , often unassembled subunits need chaperones to maintain their soluble state and eventually need to be degraded if they can not find a binding partner .\ncancer cells do nt only lose or gain whole chromosomes , they also have translocations and deletions and point mutations . we know that making and repairing dna requires a lot of nifty multi - subunit complexes ,\nso our hypothesis was that whole - chromosome abnormalities cause stoichiometric imbalances in these complexes and this leads to defects in their formation and function .\nso we re testing the idea that aneuploidy contributes to cancer because it s a mutator , rather than because it s a promoter of growth and proliferation , and we re doing more and more mouse work to answer those kinds of questions .\nbut we still use yeast to discover new properties of aneuploidy and to look at the cellular effects of changing the dosage of specific genes .\nwe started a new project on mitochondria a few years ago that i m really excited about .\none big question is : how did these two organisms start talking to each other ? did one learn english or the other learn french ? or did they resort to a more primitive sign language metabolites to talk to each other ?\nthe other thing i m fascinated by is that a large fraction of uncharacterized yeast genes localize to mitochondria .\nthat tells you there s a lot of biology in the mitochondria still to be learned .\nwhat i think is even more important is that many of these genes are not at all conserved , not even in fungi .\nso here are all these very new , very fast - evolving genes and nobody knows what they do !\nusually when people hear that a gene is not conserved , they run ! arrgh !\nit s something yeast specific ! but in this particular instance i think it s important and suggests mitochondria are still battling it out with the nucleus .\none way to look at it is to say the nucleus and mitochondria are not really symbiotic .\nif mitochondria do nt get anything out of the relationship , they are really just slaves to the nucleus .\nso the mitochondria are trying to escape the reign of the nucleus and the nucleus is fighting back in an arms race . and\nif we can understand what all these nonconserved mitochondrial genes are doing , we can begin to find the frictions that still exist between the interests of the nucleus and the mitochondria .\ni m totally fascinated by understanding how these different entities interact with each other inside a single cell .", "answer": "the genetics society of america medal is awarded to an individual for outstanding contributions to the field of genetics in the past 15 years . \n recipients of the gsa medal are recognized for elegant and highly meaningful contributions to modern genetics . \n the 2014 recipient , angelika b. amon , has uncovered key principles governing the cell cycle and was the first to demonstrate a connection between the physical completion of anaphase and the initiation of mitotic exit . \n more recently , her research has focused on the consequences of aneuploidy . \n genetics spoke with dr . \n amon about her approach to science and what is next on the horizon .", "id": 174} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncavernous hemangioma is a benign vascular malformation and belongs to a wide and continuous overlapping spectrum of hamartomas .\nmost cavernous haemangiomas occur in the vertebral body and may extend into the epidural space .\npurely extradural cavernous hemangiomas without any vertebral body involvement is extremely rare and accounts for only 4% of all extradural spinal tumors and 12% of haemangiomas occurring extradurally .\nwe herein present a rare case of extradural dumbbell lumbar ( l3 ) cavernous hemangioma with paraspinal extension .\na 52-year - old female presented with insidious onset progressive low backache with pain radiating to whole of left lower limb associated with paraesthesias for two months .\nleft lower limb power was 4/5 in hip flexion , extension , abduction and adduction , 4/5 in knee flexion and extension , subtle weakness in ankle flexion and extension and great toe extension with hypotonia .\nthe reflexes of left lower limb were sluggish whereas on right side they were brisk ( normal ) . sensory examination\nrevealed impairment of all the modalities of sensations ( pin prick , touch , temperature , vibration- impaired upto anterior superior iliac spine ) from l2 to s4 dermatomes on left side .\nmagnetic resonance imaging of lumbar spine revealed an irregularly shaped , well defined extradural lesion at l3 vertebral level indenting the body , displacing the thecal sac posterolaterally and extending into left paraspinal region through l3- 4 neural foramen .\nlesion was isointense on t1w , hyperintense on t2w images with strong homogenous enhancement on gadolinium contrast study [ figure 1 ] .\nprovisional preoperative diagnosis of schwannoma was considered . though the clinical findings and radiology were not concordant ,\nthe patient was suggested surgical intervention for the presence of enhancing mass lesion noted on the imaging with guarded prognosis .\nshows irregularly shaped well defined extradural lesion ( arrows ) , hypointense on t1w ( a ) , hyperintense on t2w ( b ) images with homogenous contrast enhancement ( c , d , e ) and paraspinal transforaminal extension ( d , e ) the patient underwent left hemilaminectomy from l2 to l4 .\nthere was an extradural , brownish red , highly vascular mass located anterolateral to thecal sac at l3 vertebral body with well defined capsule around it .\nleft l3 nerve root was pushed superiorly by the tumor and it was not arising from any neural tissue .\nit was dissected clear from the l3 nerve and the dura keeping the dissection over the coagulated capsule .\nthe spinal component of the lesion was excised in toto until the neural foramen , where it was coagulated and was cut sharply leaving behind the extra - foraminal portion .\nmicroscopic examination revealed numerous dilated vascular channels of variable sizes lined by a single layer of flattened epithelial cells and filled with blood elements .\ninterspersed thick hyalinised blood vessels and mature adipose tissues were noted [ figure 2 ] .\nradiotherapy was administered to the residual paraspinal portion of tumor [ figure 3 ] . for radiotherapy ,\nthe patient was immobilised in a vacuum locking device and ct simulation was done in the treatment position .\nmargin of 1 cm was added to the post contrast t1w mri to obtain the clinical target volume ; planning target volume was obtained by adding a margin of 0.5 cm to the clinical target volume .\nthree dimensional conformal radiotherapy was planned on eclipse planning system ( varian medical systems , palo alto , ca ) on linear accelerator ( clinac ix- 3665 ) using 6 mv x rays .\nthe dose prescription was 40 gy , 2 gy per fraction , 20 fractions given five days a week over five weeks .\n( a , b ) the proliferating and anatomizing capillary channels lined by endothelial cells ( h and e , 100 ) shows postoperative changes ( arrow ) in spinal canal and residual tumor in paraspinal region\ncavernous hemangioma is a benign vascular malformation , also known as cavernous malformation , cavernous angioma or cavernoma .\nthe cavernous hemangiomas occur throughout the neuroaxis including both intracranial and spinal compartments . according to location ,\nits incidence in supratentorial , infratentorial and spinal compartments is 80% , 15% and 5% respectively .\npurely extradural spinal cavernous hemangiomas are rare and the extension through intervertebral foramen into extraspinal region ( dumbbell ) is still rarer . in that case , it can be confused with commonly diagnosed nerve sheath tumors .\nthe onset of symptoms in these spinal cavernomas may be acute , progressive or remittent , depending on the biological behavior of the tumor .\nlumbar extradural hemangiomas behave differently , not only from intramedullary cavernous hemangiomas but also from extradural cavernomas of other spinal locations .\npurely extradural hemangiomas should be included in the differential diagnosis of lumbar extradural soft - tissue lesions .\nin contrast to intracerebral cavernous hemangiomas , the patterns of density on ct scans and signal intensity on mr images are more homogenous in extradural hemangiomas .\nanother point of differentiation is the absence of low signal rim ( hemosiderin ) which is usually seen in intraaxial spinal cord cavernomas . as seen in present case , extradural cavernous hemangiomas\nare usually isointense on t1w and hyperintense on t2w images and show homogenous contrast enhancement because of the presence of sinusoidal channels .\nthe lesion should be differentiated from other epidural neoplastic or inflammatory conditions , such as meningioma , neurofibroma , lymphoma , hemorrhagic vascular mass , granuloma and angiolipoma .\ncomplete and in toto excision of the lesion should be attempted for clinical improvement ; however , in case of subtotal excision , adjuvant radiotherapy is advised .\nradiosurgery as primary or adjuvant therapy is increasingly becoming an option as advances in radiosurgical equipment are enabling safe and accurate targeting of lesions .\nthough purely extradural cavernomas are rare in occurrence , they should be considered as possible differential diagnosis of dumbbell lesions of spine in view of operative nuances ( especially massive haemorrhage ) and management thereof .", "answer": "a 52-year - old female presented with slowly progressive left lower limb polyradiculopathy . \n mri of the lumbar region revealed an extradural dumbbell mass at l3 vertebral level , isointense on t1w and hyperintense on t2w images with homogenous contrast enhancement and extending into paraspinal region through left l3/4 foramen . \n l2 to l 4 left hemilaminectomy and excision of intraspinal part of tumor was performed . \n histopathological examination revealed presence of cavernous hemangioma . \n this case is reported because of its rarity , unusual dumbbell shape of lesion and difficulty in making a preoperative diagnosis without a coexisting bone lesion .", "id": 175} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe diagnosis of rabies is not very difficult when associated with the classical features of excitations or phobias ( aerophobia , hydrophobia ) .\nbut it can be quite challenging when presented as acute flaccid paralysis ( afp ) .\nwe report here two cases of paralytic rabies who received four doses of postexposure ( grade iii dog bite ) vaccination without rabies immunoglobulin .\nparalytic rabies occurring after postexposure antirabies vaccination creates a diagnostic dilemma as vaccine - induced gbs becomes a distinct possibility .\na ten year - old boy presented with sudden weakness of both lower limbs for two days .\nhe also had a history of fever , vomiting , and back pain for three days .\nhis past history elicited an incident of an unprovoked bite by a street dog in his right hand ( grade iii ) three weeks back .\nfour doses of purified chick embryo cell ( pcec ) antirabies vaccine were administered according to schedule in the deltoid , starting from the day of the bite .\nthe patient had complained of back pain , but there was no typical history of pain , tingling , numbness at the site of the bite , hydrophobia , or behavioral changes .\nhis temperature was 39.5c , pulse rate was 110/min , blood pressure 100/70 mm hg , respiratory rate 30/min , and spo2 96% . neurological examination detected grossly reduced muscle tone and power ( lower limb 2/5 , upper limb 3/5 ) with areflexia ( both superficial and deep tendon reflexes were absent ) in all four limbs and the trunk along with urinary incontinence .\nthe failure to administer rig after the grade iii bite favored a provisional diagnosis of paralytic rabies was made even though the classical symptoms of rabies were absent .\nalthough rare with the modern cell culture vaccines , the possibility of vaccine - induced gbs was also considered .\nlaboratory investigations showed hemoglobin : 11.5 g / dl , white cell count : 70000/cu.mm ( neutrophil : 58% , lymphocyte : 40% , eosinophil : 2% ) , platelet count : 1,90000/cu.mm .\ncerebrospinal fluid analysis showed cell count : 10/cu.mm ( all lymphocytes ) , protein : 50 mg / dl , and sugar : 80 mg / dl ( no albumino - cytological dissociation ) .\nthe electrophysiological test designed to identify features of demyelination ( slowing of nerve conduction velocity with marked prolongation of distal latencies and occasional conduction block ) , was inconclusive .\nserum electrolytes were normal na : 136 meq / l , k : 5 meq / l .\nliver function , renal function tests , and repeat csf examination on the 7 day were unremarkable .\nconservative management was started but rapid progression of paralysis occurred over the next two days .\nintravenous immunoglobulin ( 2 g / kg / total dose ) was given over 12 hours for the sake of caution , but there was no improvement and the patient succumbed on the 10 day of onset of the disease .\ndue to inadequate stool collection by the afp surveillance worker , all the documents were sent to the national expert committee ( national polio surveillance project ) as a special case .\nthey classified the case as being nonpolio and as paralytic rabies . a six year - old girl presented with sudden onset of quadriparesis for one day , preceded by fever , myalgia , and vomiting for four days .\nthere was also a history of a dog bite in her right upper arm ( grade iii bite ) three weeks back .\nthe child was given the pcec vaccine as per schedule in the deltoid and received a total of four doses before the development of any symptoms .\nthe patient was treated conservatively , but the clinical features and the progression of disease was similar to the first case , except for the presence of myoedema , a striking feature of rabies . in spite of good supportive measures , she expired on the 12 day of disease onset .\nresults of laboratory investigations on the 11 day of the illness were also quite similar to the first case .\nneutralizing antibodies to rabies virus were detected in both serum and csf by the rapid fluorescent focus inhibition test ( rffit ) .\na ten year - old boy presented with sudden weakness of both lower limbs for two days .\nhe also had a history of fever , vomiting , and back pain for three days .\nhis past history elicited an incident of an unprovoked bite by a street dog in his right hand ( grade iii ) three weeks back .\nfour doses of purified chick embryo cell ( pcec ) antirabies vaccine were administered according to schedule in the deltoid , starting from the day of the bite .\nthe patient had complained of back pain , but there was no typical history of pain , tingling , numbness at the site of the bite , hydrophobia , or behavioral changes .\nhis temperature was 39.5c , pulse rate was 110/min , blood pressure 100/70 mm hg , respiratory rate 30/min , and spo2 96% . neurological examination detected grossly reduced muscle tone and power ( lower limb 2/5 , upper limb 3/5 ) with areflexia ( both superficial and deep tendon reflexes were absent ) in all four limbs and the trunk along with urinary incontinence .\nthe failure to administer rig after the grade iii bite favored a provisional diagnosis of paralytic rabies was made even though the classical symptoms of rabies were absent .\nalthough rare with the modern cell culture vaccines , the possibility of vaccine - induced gbs was also considered .\nlaboratory investigations showed hemoglobin : 11.5 g / dl , white cell count : 70000/cu.mm ( neutrophil : 58% , lymphocyte : 40% , eosinophil : 2% ) , platelet count : 1,90000/cu.mm .\ncerebrospinal fluid analysis showed cell count : 10/cu.mm ( all lymphocytes ) , protein : 50 mg / dl , and sugar : 80 mg / dl ( no albumino - cytological dissociation ) .\nthe electrophysiological test designed to identify features of demyelination ( slowing of nerve conduction velocity with marked prolongation of distal latencies and occasional conduction block ) , was inconclusive .\nserum electrolytes were normal na : 136 meq / l , k : 5 meq / l .\nliver function , renal function tests , and repeat csf examination on the 7 day were unremarkable .\nconservative management was started but rapid progression of paralysis occurred over the next two days .\nintravenous immunoglobulin ( 2 g / kg / total dose ) was given over 12 hours for the sake of caution , but there was no improvement and the patient succumbed on the 10 day of onset of the disease .\ndue to inadequate stool collection by the afp surveillance worker , all the documents were sent to the national expert committee ( national polio surveillance project ) as a special case .\na six year - old girl presented with sudden onset of quadriparesis for one day , preceded by fever , myalgia , and vomiting for four days .\nthere was also a history of a dog bite in her right upper arm ( grade iii bite ) three weeks back .\nthe child was given the pcec vaccine as per schedule in the deltoid and received a total of four doses before the development of any symptoms .\nthe patient was treated conservatively , but the clinical features and the progression of disease was similar to the first case , except for the presence of myoedema , a striking feature of rabies . in spite of good supportive measures , she expired on the 12 day of disease onset .\nresults of laboratory investigations on the 11 day of the illness were also quite similar to the first case .\nneutralizing antibodies to rabies virus were detected in both serum and csf by the rapid fluorescent focus inhibition test ( rffit ) .\nthere are two forms of human rabies : i ) the well - known encephalitic ( furious ) and ii ) the paralytic ( dumb ) rabies .\nthe encephalitic form starts with fever , malaise , pharyngitis , and paraesthesia at the site of the bite followed by the classical neurological symptoms of hydrophobia , aerophobia , agitation , hypersalivation , and seizures .\nthis is followed by paralysis and coma ; death is usually due to respiratory failure .\nthe second clinical form of rabies , paralytic ( dumb ) or guillain - barr - like , is characterized by progressive paralysis without an initial furious phase . even though the paralytic rabies is unfamiliar to health care providers , 2030% of rabies victims present in this manner .\nparalytic rabies is more common after rabid vampire bat bites and in persons who have received postexposure vaccination .\ndistinction of paralytic rabies from gbs may be difficult , although individuals with gbs usually do not have urinary incontinence , which is common in rabies . in our two cases ,\nfever at the onset of disease , the absence of albumin - cytological dissociation , even repeat csf examination and persistent urinary incontinence was against the diagnosis of vaccine - induced gbs .\ndifferent sites of neural involvement and possibly different neuropathogenetic mechanisms may explain the clinical diversity in human rabies .\nit is unclear whether weakness results from the involvement of anterior horn cells or of motor nerve fibers .\nmost likely , peripheral nerve dysfunction , due to demyelination , contributes to the weakness seen in paralytic rabies . on the other hand ,\nprogressive focal denervation starting at the bitten segment , was evident in furious rabies , even in the absence of demonstrable weakness .\nintense inflammation of the spinal nerve roots was observed to a greater extent in paralytic rabies patients .\ninflammation was mainly noted in the spinal cord segment corresponding to the bite in all cases .\nhowever , central chromatolysis of the anterior horn cells could be demonstrated only in furious rabies patient . in both patients , ncv findings revealed features of demyelination which may occur in paralytic rabies as well as in gbs .\nstudies conducted in the us by the center for disease control and prevention ( cdc ) have documented that a regimen of one dose of rig and five doses of the human diploid cell culture vaccine ( hdcv ) over a period of 28 days was safe and induced an excellent antibody response in all recipients .\nclinical trials with rabies vaccine adsorbed ( rva ) and purified chick embryo cell ( pcec ) vaccine have also demonstrated immunogenicity equivalent to that of hdcv .\nmany individuals did not receive immunoglobulin where indicated and some of them received the vaccine in the gluteal region instead of in the deltoid . although both of our patients had grade iii dog bite for which rig is strongly recommended , they only received the vaccine in the deltoid region without rig .\nneurological reactions following newer vaccine administration have been extremely rare . after millions of vaccinations worldwide , three guillain - barr type paralytic reactions have been described , and all cases recovered completely . if our patients had vaccine - induced gbs , definitely they were improved by good supportive measures . during the early stages of paralytic rabies ,\nnotable signs include myoedema , particularly in the region of the chest , deltoid muscles , and thighs . however , this phenomenon , a brief , unpropagated , localized muscle contraction that appears in response to percussion with a tendon hammer , is not a confirmatory sign of paralytic rabies but was present in our 2 case .\nif there is an inadequate stool sample with residual paralysis , death of the patient , or loss to follow - up at the time of afp surveillance , the case is referred to the national expert committee ( national polio surveillance project ) review for final classification as nonpolio afp or compatible with poliomyelitis . in our first case\n, there was inadequate stool sampling , so it was reviewed by the expert committee and declared to be paralytic rabies .", "answer": "two clinical forms of rabies are recognize : i ) a furious form associated with classical signs of excitation or phobic symptoms , ii ) dumb rabies ( paralytic rabies ) characterized by progressive paralysis without an initial furious phase wherein distinction from guillain - barr syndrome may be difficult . \n paralytic rabies is more common in persons who have received postexposure vaccination . \n we report here the diagnostic dilemma of two cases of acute flaccid paralysis due to rabies .", "id": 176} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmalignant melanoma is an aggressive skin cancer accounting for about 4.5% of all new cancer cases and 1.7% of all cancer deaths in the united states .\nmalignant melanoma can metastasize to various sites including , but not limited to , the brain , lung , and gastrointestinal tract .\nintra - thoracic metastases in malignant melanoma most commonly present as multiple or solitary pulmonary nodules and rarely as isolated pleural effusions .\nthough there are few reported cases of recurrent malignant melanoma presenting with isolated pleural effusion , what makes our case intriguing , is its presentation in the context of coexisting chronic lymphocytic leukemia ( cll ) .\na 65-year - old caucasian woman presented in march 2007 with a 3-month history of painless left - sided cervical lymphadenopathy .\nshe denied any associated fevers , chills , loss of weight , dyspnea , dysphagia , or any other symptoms .\nthe patient 's surgical history was pertinent for a completely resected stage ia melanoma over the left shoulder 16 years before this presentation .\nphysical exam revealed enlarged and non - tender cervical and axillary lymph nodes without splenomegaly .\na complete blood picture showed a white blood cell count of 14.7 103/l , an absolute lymphocyte count of 7.35 103/l , hemoglobin of 13.8 g / dl , a platelet count of 258 103/l , and lactate dehydrogenase of 291 u / l .\nflow cytometry of the peripheral blood demonstrated a monoclonal lymphocyte population expressing cd5 , cd19 , cd20 , cd24 , cd43 , and cd52 with lambda light chain restriction and no increase in cd34-positive blasts .\nbased on the above findings , the patient was diagnosed with rai stage i cll and placed under observation .\ntwo years after her initial diagnosis , the patient presented with progressive dyspnea , associated with pleuritic chest pain and a 20 lbs weight loss over a period of 3 months .\nphysical examination revealed increased axillary and cervical lymphadenopathy and decreased breath sounds over the right lung .\nwhite blood cell count was noted to be 53.4 103/l , and she had an absolute lymphocyte count of 40.7 103/l .\nthe pleural fluid analysis was consistent with an exudative effusion , with increased atypical lymphocytes .\nthe majority of the lymphocytes were cd4 + t - lymphocytes ( cd4:cd8 in a ratio of 15 : 1 ) , but polymerase chain reaction failed to show any clonal t - cell receptor- or t - cell receptor- gene rearrangements .\nsecondary to rapid reaccumulation of pleural fluid , increasing lymphadenopathy , and rapid doubling time of lymphocyte count , the decision to treat symptomatic cll was made .\nchemotherapy with pentostatin , cyclophosphamide , and rituximab did not result in any meaningful clinical response .\nas the patient 's pleural effusion was refractory to cll treatment , video - assisted thoracoscopic surgery was performed , which demonstrated diffuse nodular thickening of both visceral and parietal layers of the pleura ( fig .\na biopsy of these lesions revealed enlarged cells with an increased nuclear - cytoplasmic ratio and pleomorphic nuclei with occasional cherry red nucleoli ( fig .\nelectron microscopy revealed type ii melanosomes with cross - striated lattice in an enclosed membrane ( fig .\n1e ) , type iii melanosomes with increased deposition of electron - dense melanin , and type iv melanosomes with highly electron - dense melanin ( fig .\ncomputed tomography of the chest revealed extensive lobulated tumor lining the entirety of the right parietal pleural surface without any evidence of parenchymal involvement .\nthe patient 's medical condition rapidly declined , and she ultimately succumbed to death before initiation of any therapy .\ncll is a low - grade lymphoproliferative state characterized by the accumulation of functionally incompetent monoclonal b - lymphocytes .\nimmunosuppression in cll is hypothesized to be a result of immunosuppressive factors released by the neoplastic b cells that downregulate t - cell function .\nloss of chain and costimulatory molecule cd28 on t - cell lymphocytes along with reduced il-4 and ifn- expression by cd4 + t cells in patients with cll also seem to play a role in the t - cell dysfunction in cll .\nthe immune system plays a crucial role in immunosurveillance against malignant transformation and tumor propagation and , hence , t - cell dysregulation and dysfunction in cll patients increase their risk of recurrent or secondary malignancies . in several retrospective studies involving patients with cll ,\nincreased incidence of secondary cancers like kaposi sarcoma , head and neck cancer , lung cancer , and malignant melanoma was noted [ 7 , 8 ] .\nreported that the overall risk of any second - incident cancer in cll patients was higher than in the general population ( second - incident cancer : 2.17 , 95% ci 2.072.27 ) , and the risk of melanoma was found to be 7.74 times that of the general population ( 95% ci 6.858.72 ) .\nhence , prompt detection and treatment of the malignant melanoma are crucial in patients with cll .\nmetastases to various viscera have been known to occur even after the resection of the original tumor . however , isolated pleural metastasis with pleural effusion as a metastatic recurrence is very rare . in a series of 130 patients with malignant melanoma and thoracic complications ,\n15% were found to have pleural effusions , and less than 3% had isolated and unilateral pleural effusion .\nonly a handful of cases with recurrent isolated metastatic pleural involvement presenting after a prolonged period after resection of the primary lesion were reported , with the longest reported progression - free survival being 14 years [ 12 , 13 ] . in our patient , isolated pleural metastases were noted 16 years from the complete resection of the skin lesion . computed tomography of the chest may aid in the diagnosis of pleural metastasis by demonstrating thickened pleura and parenchymal involvement .\npositron emission tomography may also aid in the detection of fdg - avid pleural metastasis .\nthoracentesis , unless contraindicated , should be considered in all cases of suspected malignant pleural effusions .\neffusions in malignant melanoma are relatively richer in cd8 + than in cd4 + t - lymphocytes . in our case , the majority of the cells in the pleural effusion expressed cd4 + , and only 12% of the lymphocytes expressed the markers expressed by tumor cells .\nthe latter can be explained by the deficient migratory capacity of the b - cll cells , which might have led to a relative enrichment of reactive t cells .\nvideo - assisted thoracoscopic surgery and pleural biopsy may be useful for diagnosis and to perform molecular studies .\nconcomitant history of cll , pleural fluid studies suggestive of cll , and a distant history of malignant melanoma made the diagnosis challenging in our patient .\nwe speculate that immune dysregulation associated with cll could have led to recurrence of melanoma in our case .\nour case underlines the importance of having a suspicion for malignant melanoma in patients presenting with isolated pleural effusion , especially in the setting of an underlying lymphoproliferative disorder and a previous history of melanoma .", "answer": "isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma . \n we report an unusual case of a patient with chronic lymphocytic leukemia ( cll ) and recurrent pleural effusions . \n the pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of cll . however \n , chemotherapy with pentostatin , cyclophosphamide , and rituximab did not result in any meaningful clinical response . \n a video - assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma . \n our case underlines the importance of having a suspicion for secondary causes of effusion in patients with cll . \n we briefly discuss the mechanisms of an increased incidence of secondary cancers in cll and the diagnosis of isolated pleural metastases in malignant melanoma .", "id": 177} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmicroleakage between the root canal filling and root - canal walls may adversely affects the results of root - canal treatment.1 apical leakage is considered to be common cause of endodontic failure.2 hence , different endodontic filling materials , sealers and techniques have been introduced to the dental community in an attempt to improve apical seal.1 various materials have been used in root canal treatment in an attempt to achieve success .\nbut , a combination of gutta - percha and a sealer are used most commonly .\ngutta - percha is considered an impermeable core material ; therefore , leakage through an obturated root canal is expected to take place at the interfaces between the sealer and dentin or the sealer and gutta - percha , or through voids within the sealer.3 apical sealing is desirable to prevent passage of bacteria and their endodotoxin apically . in vitro evaluation of apical dye penetration\nis used to estimate the sealing ability which is corresponding to in vivo amount of micro leakage with particular sealer.2 many techniques were used to evaluate the leakage of sealers such as ; colored dye penetration radio labeled tracer penetration dissolution of hard tissue clearing of teeth , spectrometry of radioisotopes electrochemical and gas chromatography .\nhowever , many studies showed no significant difference between these techniques.1 the aim of this in vitro study was to quantitatively evaluate the sealing properties of three different root - canal sealers ; tubliseal , sealapex and ah26 using a spectrophotometric method .\nthirty - six extracted sound mandibular molar natural teeth specimens with complete root and free from caries or cracks were collected , stored , disinfected and handled as per the recommendations and guidelines laid down by occupational safety and health administration and centers for disease control and prevention.4 the teeth were then placed in 0.9% physiologic saline solution for ten days prior to access cavity preparation .\nthe samples were divided into three experimental groups ; group i : sealapex , group ii : tubliseal and group iii : ah26 with 12 samples in each group .\nthe samples were then coated with nail varnish all over the root surface except 2 mm around the apical foramen . 2 ml of freshly prepared 2% methylene blue dye was taken in each vial and the apical third of the root was suspended in the dye for 72 h. samples were washed with distilled water , nail varnish removed and then placed in 20 ml of 35% nitric acid for 72 h. standard solutions of 1% , 0.5% , 0.2% , 0.05% , 0.02% and 0.01% of methylene blue in 35% nitric acid were prepared and stored for 72 h. the standard solutions and the nitric acid solutions were filtered and centrifuged for 1 min after 72 h. the supernatant was subjected to spectrophotometric analysis using a filter of 670 nm .\nthe amount of leakage was extrapolated from a standard linear regression curve constructed from stock standard methylene blue dye solutions .\nobtained data were statistical analyzed with kruskal wallis and mann whitney u - tests using spss software version 20 ( ibm ) .\nthe results of the quantitative evaluation of the sealing properties of the three root - canal sealers are shown in table 1 .\n, tubliseal showed a significant difference ( p > 0.005 ) . in comparison to sealapex\ncomparisons made between tubliseal and ah26 showed no significant difference ( table 2 , chart 1 ) . mean and standard deviation values of volumetric dye penetration in groups with reference to transmission .\nthree - dimensional obturation of the root canal system with a fluid impervious seal is an important factor for successful endodontic therapy .\nthe root canal filling should seal the canal both apically and coronally to prevent the passage of microorganism to apex or vice versa.5 most reliable method is the use of gutta - percha cones with sealer cement .\nsealers based on zinc oxide - eugenol ( tubliseal ) , calcium hydroxide ( sealapex ) , epoxy resins ( ah26 ) were included in the present study . in present quantitative dye leakage study ,\ntubliseal demonstrated least dye leakage in comparison with other experimental groups ( table 1 ) .\nour results were in contrary to study by masoud and saleh where they found more microleakage in tubliseal group than other groups.6 sealapex is a calcium hydroxide type sealer .\ncalcium hydroxide used as root canal sealer since it stimulates periapical tissues in order to maintain health or promote healing and secondly for its antimicrobial effects.7 it has been observed in some studies that , calcium hydroxide sealers showed a significant volumetric expansion during setting because of water absorption , which increases its solubility .\nthe present in vitro investigation indicated maximum leakage value with sealapex among the experimental groups . in a contradictory to our results , cobankara et al .\n( 2006 ) observed sealapex with better apical sealing than the other sealers ( ah plus and rc sealer ) at 7 , 14 , and 21 days.3 ah26 is an epoxy resin based sealer that provides easy handling characteristics , good flow , good sealing to dentin and prominent antimicrobial activity.6 kumar et al . observed more micro leakage with zinc oxide - based sealer and least with resin based sealers , this is contradictory to our study.8 in our study , there was no statistical significant difference between tubliseal and ah26 in micro leakage .\nobserved least amount of dye penetration for ah plus and endorez group.9 even though , the current study did not indicate any statistically significant difference between ah26 and sealapex , it is time to question the overall efficacy of calcium hydroxide sealers on the grounds that the reparative and the calcification capabilities attributed to calcium hydroxide are generally desirable before completing the obturation .\nah26 , resin based sealer provided a better apical seal when compared with sealapex even though the results were statistically not significant .\nit mixes easily , flows well , and has ample working time , good radio - opacity , comparable solubility , good adhesion and good biocompatibility.3 in the present study , there was no significant difference between group ii and iii and group i and iii .\ndid nt find any significant difference between the tested three groups ; sealer 26 , enfoflas and resin group .\nbut they observed higher microleakage in sealer 26 group compared with control.11 joseph and sing evaluated the apical sealing with four root canal sealers ; ah26 , sealapex , endoflas fs and ah plus and observed no significant differences between all groups except between ah plus and endoflas.5 nagas et al .\nobserved significantly lower overall leakage with ah plus group , whereas no difference was found between master cone points.12 kopper et al . observed significant dye penetration for ah plus , endofill and sealer 26.13 cobankara et al .\nobserved better sealing values for roekoseal after 21 days when compared to ketac - endo and ah plus , and there was no statistically significant difference.1 dultra et al . found no statistical difference between groups for apical leakage ( endofill , ah plus , endorez and epiphany).14 in addition , before accepting a new material for routine clinical use further experiments\nshould also be performed to evaluate the other aspects of the materials physical and biological properties such as biocompatibility , solubility , disintegration , radio - opacity and dimensional stability . however\n, these in vitro studies do provide comparative information of the relative performance of sealers tested under the same conditions in each particular study and clinicians can use this information to possibly choose a better sealer .\nin the present study , tubliseal sealer showed least microleage compared with sealapex and ah26 sealer .\nit is important to remember before declaring any root canal sealer as most acceptable that the results of the dye penetration studies indicate only the relative sealing ability of root canal fillings in vitro and they do not indicate their ability to prevent the penetration of bacteria into filled root canals in vivo .", "answer": "background : the aim of this study was to quantitatively analyze the amount of dye leakage with ah26 , sealapex and tubliseal sealers in endodonticaly treated teeth.materials and methods : a total of 36 extracted mandibular molar specimens were divided into three groups ; group i : sealapex , group ii : tubliseal , group ii : ah26 with 12 samples in each group . \n standard access cavity and biomechanical preparation was done with step back flare technique . \n obturations were done using respective sealers in the three different groups . \n then , samples were subjected to spectro photometric analysis using a filter of 670 nm . \n spectrophotometric analysis was performed to quantitatively analyze the amount of dye leakage with all three sealers.results:tubliseal exhibited the least microleakage . in comparison to sealapex \n , tubliseal showed a significant difference . compared to sealapex \n , ah26 showed no significant difference . \n comparisons made between tubliseal and ah26 showed no significant difference.conclusion:in the present study , tubliseal sealer showed least microleage compared with sealapex and ah26 sealer .", "id": 178} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhile drugs can cause acute rhabdomyolysis individually , they can also interact with other drugs by cytochrome p450 and p - glycoprotein mechanisms to bring on the syndrome.clinicians should evaluate drug interactions in patients taking two or more medications .\nacute rhabdomyolysis ( ar ) is a clinical syndrome that occurs when the electrolytes and myoglobin that are released upon skeletal muscle damage enter into the circulation system .\nthere are several ways in which ar may occur , one of which is drugs ( fig . \n1etiology of acute rhabdomyolysis and its complications etiology of acute rhabdomyolysis and its complications a comprehensive study was carried out in 2011 using 20042009 data of the us food and drug administration ( fda ) to reveal which drugs may be associated with rhabdomyloysis .\nthe etiologies of 16,435 drug - induced cases of rhabdomyloysis involved hmg - coa reductase inhibitors or statins ( n = 4325 , 26.3 % ) as the first suspect .\na total of 100 cases were reported for diclofenac and 99 for omeprazole , a proton pump inhibitor , while there were no reports of cases associated with pantoprazole .\nthe cases of drug - induced rhabdomyolysis in previous literature were also associated with statins , and the frequency is similar to that reported in the abovementioned report . that said , drug interactions could not be assessed because the fda data did not include that level of systematic information .\nthe gastric side effects of non - steroidal anti - inflammatory drugs ( nsaids ) are well known , and their concomitant or subsequent combination with proton pump inhibitors is common . a review of adverse drug reactions , creatinine kinase elevations , and muscle events , including muscle weakness , myopathy , myositis , and polymyositis , analyzed such multiple drug regimens and found that the addition of pantoprazole to a treatment regimen was the cause of all muscle events , aside from myalgia .\na 45-year - old man was referred to hospital complaining of fatigue and extensive body pain .\nhis medical history included stress - induced headaches that had been present for almost the entire previous year , for which he began using diclofenac at 50 mg / day as the frequency of headaches had increased during the prior month .\nhe was referred to a physician for pyrosis , 1 week prior to presenting at the hospital , and was prescribed pantoprazole at 40 mg / day .\nhe started to experience pain in his leg muscles on the fourth day of the diclofenac and pantoprazole combination regimen and used two 50-mg doses of diclofenac to control the pain .\nthe muscle pain became more widespread on the fifth day , and the patient also developed fatigue .\nan examination revealed a blood pressure of 120/80 mmhg and a pulse of 76 bpm , full and rhythmic .\nmuscular strength was good ; however , the patient complained of muscle tenderness upon palpation .\nneurological and general system examinations were normal ; no abnormal findings were seen in an electrocardiogram ; and an abdomen ultrasound revealed no pathology , aside from an abdominal gas distention . a laboratory analysis revealed high levels of muscle destruction products , the foremost of which was creatinine kinase ( table 1 ) .\nglucose , urea , creatinine , cholesterol levels , amylase , direct and indirect bilirubin , electrolytes , anti - streptolysin o , c - reactive protein , rheumatoid factor , and thyroid hormones were all within their normal ranges.table 1laboratory parameters of patientadmission7 days afterreference rangeglucose ( mg / dl)96n / a70105alp ( alkaline phosphatase ) ( iu / l)565164306sgpt ( iu / l)4512042sgot ( iu / l)8814534ck ( iu / l)31146724190creatinine ( mg / dl)0.760.670.751.25crp ( mg / dl)0.880.5905ldh ( iu / l)230168125220 \n alp alkaline phosphatase , ck creatine kinase , crp c - reactive protein , ldh lactate dehydrogenase , n / a not available , sgot serum glutamic oxaloacetic transaminase , sgpt serum glutamic pyruvic transaminase laboratory parameters of patient \n alp alkaline phosphatase , ck creatine kinase , crp c - reactive protein , ldh lactate dehydrogenase , n / a not available , sgot serum glutamic oxaloacetic transaminase , sgpt serum glutamic pyruvic transaminase a cardiac pathology was excluded because the electrocardiographic assessments and cardiac sounds were normal , and because the patient did not describe any pain that would indicate an infarct , and test results and findings were stable on the following days .\nar was considered as a pre - diagnosis , as there was a chronologic alignment between the patient s clinical representation and the medications he used , and this was supported by the laboratory parameters .\nboth medications were discontinued and the patient was followed up for 1 week , during which no medical interventions were carried out , aside from a recommendation of general hydration .\nthe ar diagnosis was confirmed because his complaints disappeared , with his laboratory values returning to the normal range , a stable electrocardiogram , and other systemic examinations being found within normal ranges .\nto date , among the cases involving nsaids , two cases were reported that include diclofenac - induced rhabdomyloysis [ 4 , 5 ] . the patient detailed in this study was referred with extensive pain and fatigue , and represents the third case in which rhabdomyloysis developed while using 100-mg / day diclofenac tablets .\nthe other two cases were induced by diclofenac alone , with no interaction with other drugs . of these , one patient was admitted with pain that increased after the patient took 200 mg of diclofenac within 2 days ( 50 mg tablet / twice a day ) for joint pain .\nthe other case involved a patient who used diclofenac to ease an acute exacerbation of gout .\nthe patient was referred to a physician on the 13th day of intramuscularly self - administered diclofenac at 75 mg per day for 6 days , followed by 75 mg orally three times a day for 7 days . unlike the previous case , this patient was referred to the hospital because of erythematous pruritic eruptions that developed on various parts of his body . while drugs can cause ar individually , they can also interact with other drugs to bring on the syndrome .\nthe cyp1 , cyp2 , and cyp3 gene families are overall responsible for drug metabolism , and the similarities between the amino acid sequences within a gene family are at least 40 % , although the level of similarity may increase to 85 % between subgroups . the genetic polymorphisms in these genes\nalter the biotransformation of the drug . while fast metabolizers have increased enzyme activity , slow metabolizers show decreased enzyme activity . among these genes ,\ntheophylline , which is metabolized through this pathway , when used with erythromycin , returns to the cyp1a2 pathway and can not reach toxic concentrations [ 79 ] .\nthat said , to date , no such theory has been put forward for diclofenac and pantoprazole in the cyp enzyme system .\nthe fact that they are metabolized through the same subgroup ( 2c ) can be associated with a possible drug interaction .\nthis possibility of interaction between diclofenac and pantoprazole has been investigated in a randomized crossover trial of 24 subjects , and the results showed that the peak plasma concentrations of diclofenac are sustained in a stable range , and that diclofenac does not affect the pharmacokinetics of pantoprazole , meaning that this combination is completely safe .\nhowever , the results of an in - vitro study using diclofenac as a substrate marker for human liver microsomes suggested the contrary . according to this study , proton pump inhibitors , the strongest one being pantoprazole , carry a strong potential for drug interaction by inhibiting the activity of cyp enzymes , and it was underlined that drug interactions are significantly more pronounced in weak metabolizers with an enzyme deficiency .\np - glycoprotein ( p - gp ) is an adenosine triphosphate - dependent efflux transprotein that is found in the membranes of the enterocytes .\nit is expressed by the mdr1 gene in humans and can be found in various organs , including the liver , kidneys , intestinal region , and blood brain barrier .\np - gp actively pumps its substrates xenobiotics to the extracellular space and decreases their intracellular concentrations .\nproton pump inhibitors , including pantoprazole , anti - arrythmic drugs , anticancer drugs , antibiotics , and antidepressant drugs , inhibit p - gp , and therefore the modulation of this pump plays a crucial role in drug drug interactions [ 12 , 13 ] .\nwhile drugs can cause ar individually , they can also interact with other drugs to bring on the syndrome .\nthe cyp1 , cyp2 , and cyp3 gene families are overall responsible for drug metabolism , and the similarities between the amino acid sequences within a gene family are at least 40 % , although the level of similarity may increase to 85 % between subgroups . the genetic polymorphisms in these genes\nalter the biotransformation of the drug . while fast metabolizers have increased enzyme activity , slow metabolizers show decreased enzyme activity . among these genes ,\ntheophylline , which is metabolized through this pathway , when used with erythromycin , returns to the cyp1a2 pathway and can not reach toxic concentrations [ 79 ] .\nthat said , to date , no such theory has been put forward for diclofenac and pantoprazole in the cyp enzyme system .\nthe fact that they are metabolized through the same subgroup ( 2c ) can be associated with a possible drug interaction .\nthis possibility of interaction between diclofenac and pantoprazole has been investigated in a randomized crossover trial of 24 subjects , and the results showed that the peak plasma concentrations of diclofenac are sustained in a stable range , and that diclofenac does not affect the pharmacokinetics of pantoprazole , meaning that this combination is completely safe .\nhowever , the results of an in - vitro study using diclofenac as a substrate marker for human liver microsomes suggested the contrary . according to this study , proton pump inhibitors , the strongest one being pantoprazole , carry a strong potential for drug interaction by inhibiting the activity of cyp enzymes , and it was underlined that drug interactions are significantly more pronounced in weak metabolizers with an enzyme deficiency .\np - glycoprotein ( p - gp ) is an adenosine triphosphate - dependent efflux transprotein that is found in the membranes of the enterocytes .\nit is expressed by the mdr1 gene in humans and can be found in various organs , including the liver , kidneys , intestinal region , and blood brain barrier .\np - gp actively pumps its substrates xenobiotics to the extracellular space and decreases their intracellular concentrations .\nproton pump inhibitors , including pantoprazole , anti - arrythmic drugs , anticancer drugs , antibiotics , and antidepressant drugs , inhibit p - gp , and therefore the modulation of this pump plays a crucial role in drug drug interactions [ 12 , 13 ] .\nthe fda recommends that clinicians check cyp - mediated potential drug interactions routinely . in this case report , a case of diclofenac- and pantoprazole - induced ar is evaluated for drug - interaction mechanisms , and different perspectives are presented . while evaluating the patients with side effects of drugs ,\nthe cyp and p - gp mechanisms that play roles in drug absorption and distribution should be considered .\nwritten informed consent of the participant was obtained after the nature of the procedures had been fully explained .\nthe case report was carried out in agreement with the latest version of the declaration of helsinki .", "answer": "backgrounddrugs represent one of the etiologic causes of acute rhabdomyolysis ( ar ) with drug - induced rhabdomyolysis most commonly associated with hmg - coa reductase inhibitors . \n ar etiology can also result from the use of diclofenac , a non - steroidal anti - inflammatory drug , and omeprazole , a proton pump inhibitor . \n cases of ar triggered by pantoprazole have never before been reported , although it has been observed that its inclusion in multiple drug therapies can result in muscle events.case presentationa 45-year - old man presenting with complaints of fatigue and extensive body pain was diagnosed with acute rhabdomyolysis . \n his symptoms started on the fourth day of the concomitant use of diclofenac and pantoprazole . \n the patient was using diclofenac 50-mg tablets once daily for 1 month and pantoprazole 40-mg tablets once daily during the previous week for headaches and pyrosis , resulting in an increase in his creatinine kinase levels to 3114 iu / l ( reference range \n 24190 iu / l ) on the fifth day of concomitant use . \n his creatinine kinase levels returned to normal and his complaints disappeared after the seventh day of discontinuation of both treatments.discussiona third case of diclofenac - induced rhabdomyolysis was defined in which , different from previous cases , ar was detected during the concomitant use of diclofenac and pantoprazole . \n the timing of the symptom development and the limited number of ar cases induced by diclofenac and pantoprazole suggested a drug interaction.conclusionthe close relationship between diclofenac and pantoprazole , and the cytochrome p450 and p - glycoprotein systems offers a strong indication that a drug interaction may be occurring . \n while evaluating the side effects of drugs in patients undergoing monotherapy , clinicians should also consider the mechanisms that play a part in drug absorption and distribution .", "id": 179} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe ewing sarcoma family of tumors , including ewing sarcoma and the more differentiated counterpart , primitive neuroectodermal tumor , are the second most common primary malignancies of bone in childhood and adolescence but can also occur in the soft tissues .\nsystemic chemotherapy is aimed at treating known or micrometastatic disease as well as improving local control of the cancer .\nthe intergroup ewing sarcoma study ( int-0091 ) demonstrated that a regimen of alternating cycles of vincristine - doxorubicin - cyclophosphamide and ifosfamide - etoposide was superior to vincristine - doxorubicin - cyclophosphamide alone , leading to a 5-year event - free survival of 69% versus 54% in the standard arm .\nmore recently , a randomized trial evaluated dose intensification by interval compression ( administering cycles every 2 weeks ) and found that approach to be superior , with a 4-year event - free survival of 76% in the dose - dense arm compared with 65% in the standard 3-week chemotherapy arm .\nthis is now considered by pediatric oncologists to be the standard chemotherapy regimen for patients with ewing sarcoma , although it has not been adequately evaluated in patients older than 18 .\nalthough there have been improvements in the outcome for patients with localized disease , the outcome for patients with metastatic disease and for those who relapse is poor , with survival rates of 20% for those with metastases and 10 - 20% following a recurrence .\ntherefore , in addition to standard chemotherapeutics , future clinical trials will need to incorporate novel biologic agents in an effort to achieve further survival improvements .\nthe insulin - like growth factor ( igf ) system has two principal ligands : igf-1 and igf-2 .\nthese ligands mediate their stimulatory effects via the igf-1 receptor ( igf-1r ) , a transmembrane receptor tyrosine kinase . under normal physiologic circumstances , igf-1 and igf-2\nare stimulated by growth hormone and function in a negative feedback loop to control growth hormone release .\nthe insulin growth factor - binding proteins ( igfbps ) regulate the available free igf proteins available for igf-1r activation [ 7 - 9 ] . upon ligand binding , autophosphorylation of the igf-1r tyrosine kinase initiates activation of the mitogen - activated protein kinase and phosphoinositide 3-kinase / akt pathways , leading to proliferation , survival [ 10 - 13 ] , and enhanced angiogenesis via downstream induction of vascular endothelial growth factor .\nthe igf-2 receptor is a monomeric transmembrane protein with no kinase activity and has not been shown to play a role in the development of ewing sarcoma .\nthe pathway also has a role in promoting neuronal survival , myelination , and postnatal mammary development and lactation .\nin addition , metabolic pathways use the igf system to help integrate signals from nutrition and stress in order to shift appropriately between anabolic and catabolic states .\nhigh circulating levels of igf-1 have been associated with the risk of developing prostate , breast , or colorectal cancer .\nin addition , igf-1r expression is known to be necessary for cellular transformation and for signal transduction pathways stimulated by the igf-1r to enhance tumor cell growth and proliferation . furthermore\n, igf-1r gene expression is regulated by a number of tumor suppressors , including wt1 , brca1 , and p53 .\nthere are also data to suggest that signaling through the igf-1r enhances resistance to cytotoxic chemotherapy .\ntherefore , inhibition of the igf-1r is a potentially important therapeutic target against a variety of tumors .\nthe insulin - like growth factor ( igf ) system has two principal ligands : igf-1 and igf-2 .\nthese ligands mediate their stimulatory effects via the igf-1 receptor ( igf-1r ) , a transmembrane receptor tyrosine kinase . under normal physiologic circumstances , igf-1 and igf-2\nare stimulated by growth hormone and function in a negative feedback loop to control growth hormone release .\nthe insulin growth factor - binding proteins ( igfbps ) regulate the available free igf proteins available for igf-1r activation [ 7 - 9 ] . upon ligand\nbinding , autophosphorylation of the igf-1r tyrosine kinase initiates activation of the mitogen - activated protein kinase and phosphoinositide 3-kinase / akt pathways , leading to proliferation , survival [ 10 - 13 ] , and enhanced angiogenesis via downstream induction of vascular endothelial growth factor .\nthe igf-2 receptor is a monomeric transmembrane protein with no kinase activity and has not been shown to play a role in the development of ewing sarcoma .\nthe pathway also has a role in promoting neuronal survival , myelination , and postnatal mammary development and lactation .\nin addition , metabolic pathways use the igf system to help integrate signals from nutrition and stress in order to shift appropriately between anabolic and catabolic states .\nhigh circulating levels of igf-1 have been associated with the risk of developing prostate , breast , or colorectal cancer .\nin addition , igf-1r expression is known to be necessary for cellular transformation and for signal transduction pathways stimulated by the igf-1r to enhance tumor cell growth and proliferation .\nfurthermore , igf-1r gene expression is regulated by a number of tumor suppressors , including wt1 , brca1 , and p53 .\nthere are also data to suggest that signaling through the igf-1r enhances resistance to cytotoxic chemotherapy .\ntherefore , inhibition of the igf-1r is a potentially important therapeutic target against a variety of tumors .\nthe igf signaling pathway and , in particular , the igf-1r play a major role in the development and proliferation of ewing sarcoma .\nearly studies documented the major autocrine role of the igf-1 and igf-1r pathways in ewing sarcoma , and expression of igf-1r has been shown to be a requirement for ews / fli-1 transformation in fibroblasts .\na variety of approaches in vitro and in animal models have been undertaken to disrupt the igf-1r signaling pathway , including the development of small - molecule tyrosine kinase inhibitors ( tkis ) and anti - igf-1r antibodies . in preclinical testing\n, there was an initial difficulty in obtaining specific small - molecule kinase inhibitors of the igf-1r due to a very - high - sequence homology with kinase and atp - binding domains of the insulin receptor .\nafter initial attempts , the tki nvp - aew541 was shown to have a 27-fold increased selectivity for the igf-1r over the insulin receptor . this small - molecule tki has shown promise in preclinical models , where inhibition of migration , metastasis , and angiogenesis was seen in vitro and a significant reduction in tumor growth was seen in xenograft models .\nfurther elucidation of the metabolic alterations related to the use of tkis will be necessary prior to entry into clinical trials .\nmore recently , targeted antibodies have been shown not only to disrupt ligand - receptor binding , but also to decrease surface igf-1r expression by internalization and degradation of the antibody - bound receptor .\nhuman monoclonal anti - igf-1r antibodies have been produced by many pharmaceutical companies : imc - a12 ( imclone systems , new york , ny , usa ) , amg 479 ( amgen , thousand oaks , ca , usa ) , r1507 ( roche , basel , switzerland ) , cp-751,871 ( pfizer inc , new york , ny , usa ) , sch717454 ( schering - plough corporation , kenilworth , nj , usa ) , mk-0646 ( merck ) , and ave1642 ( immunogen , inc , waltham , ma , usa / sanofi - aventis , paris , france ) .\nthese antibodies have been tested in preclinical settings and ongoing early - phase adult studies [ 30,32 - 36 ] .\nthe sch717454 igf-1r antibody was tested against a panel of pediatric tumors by the pediatric preclinical testing program , a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models .\nintermediate or high activity was demonstrated in two of five ewing sarcoma xenografts , including one complete response .\nin addition , the imc - a12 antibody is currently under investigation in a phase ii children 's oncology group ( cog ) trial , with a stratum available for patients with ewing sarcoma . through the sarcoma alliance for research through collaboration ( sarc ) , the r1507 antibody has been tested in two phase i studies in adults .\nthe first study assessed the administration of the antibody on a 3-week basis and was well tolerated , without any dose - limiting toxicity or serious adverse events ; 11 of 26 patients were found to have stable disease , although none had ewing sarcoma . in the second study ,\nfour of eight heavily pretreated patients with ewing sarcoma demonstrated stable disease , with two of eight patients demonstrating durable partial responses .\nthe igf signaling pathway and , in particular , the igf-1r play a major role in the development and proliferation of ewing sarcoma .\nearly studies documented the major autocrine role of the igf-1 and igf-1r pathways in ewing sarcoma , and expression of igf-1r has been shown to be a requirement for ews / fli-1 transformation in fibroblasts .\na variety of approaches in vitro and in animal models have been undertaken to disrupt the igf-1r signaling pathway , including the development of small - molecule tyrosine kinase inhibitors ( tkis ) and anti - igf-1r antibodies . in preclinical testing\n, there was an initial difficulty in obtaining specific small - molecule kinase inhibitors of the igf-1r due to a very - high - sequence homology with kinase and atp - binding domains of the insulin receptor .\nafter initial attempts , the tki nvp - aew541 was shown to have a 27-fold increased selectivity for the igf-1r over the insulin receptor . this small - molecule tki has shown promise in preclinical models , where inhibition of migration , metastasis , and angiogenesis was seen in vitro and a significant reduction in tumor growth was seen in xenograft models .\nfurther elucidation of the metabolic alterations related to the use of tkis will be necessary prior to entry into clinical trials .\nmore recently , targeted antibodies have been shown not only to disrupt ligand - receptor binding , but also to decrease surface igf-1r expression by internalization and degradation of the antibody - bound receptor .\nhuman monoclonal anti - igf-1r antibodies have been produced by many pharmaceutical companies : imc - a12 ( imclone systems , new york , ny , usa ) , amg 479 ( amgen , thousand oaks , ca , usa ) , r1507 ( roche , basel , switzerland ) , cp-751,871 ( pfizer inc , new york , ny , usa ) , sch717454 ( schering - plough corporation , kenilworth , nj , usa ) , mk-0646 ( merck ) , and ave1642 ( immunogen , inc , waltham , ma , usa / sanofi - aventis , paris , france ) .\nthese antibodies have been tested in preclinical settings and ongoing early - phase adult studies [ 30,32 - 36 ] .\nthe sch717454 igf-1r antibody was tested against a panel of pediatric tumors by the pediatric preclinical testing program , a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models .\nintermediate or high activity was demonstrated in two of five ewing sarcoma xenografts , including one complete response .\nin addition , the imc - a12 antibody is currently under investigation in a phase ii children 's oncology group ( cog ) trial , with a stratum available for patients with ewing sarcoma . through the sarcoma alliance for research through collaboration ( sarc ) , the r1507 antibody has been tested in two phase i studies in adults .\nthe first study assessed the administration of the antibody on a 3-week basis and was well tolerated , without any dose - limiting toxicity or serious adverse events ; 11 of 26 patients were found to have stable disease , although none had ewing sarcoma . in the second study ,\nfour of eight heavily pretreated patients with ewing sarcoma demonstrated stable disease , with two of eight patients demonstrating durable partial responses .\nhuman monoclonal antibody therapy directed against the igf-1r holds great promise for improving the prognosis for children , adolescents , and adults with ewing sarcoma .\nthe recent data demonstrating responses in heavily pretreated patients with refractory ewing sarcoma bring a wave of excitement to move these therapies to the forefront .\nclinical trials are under way to assess the feasibility and efficacy of combining anti - igf-1r therapy with multiagent chemotherapy . over the next 5 years\n, feasibility testing will be completed , and if successful , phase iii studies will assess whether the addition of these new agents will result in therapeutic improvements .", "answer": "the insulin - like growth factor ( igf ) signal transduction pathway appears to play a key role in the development and proliferation of the ewing sarcoma family of tumors . \n integration of anti - igf-1 receptor therapy into the standard treatment for these patients is a novel approach that will likely be incorporated into future treatment to determine whether such agents will improve the outcome for patients with this malignancy .", "id": 180} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmacrolide , lincosamide and streptogramin b ( mlsb ) antibiotics are structurally different with a same mechanism of action .\nthese drugs , especially clindamycin , are alternative drugs for some staphylococcus aureus infections such as skin and soft tissue infections particularly in penicillin - allergic patients ( 1 , 2 ) .\nclindamycin resistance in s. aureus strains may be either constitutive ( cmlsb ) or inducible ( imlsb ) .\nrelapse of infection in a patient with s. aureus endocarditis was reported in 1976 ( 3 ) .\ndetection of isolates with inducible clindamycin resistance is a problematic issue for the routine diagnosis , because they are erythromycin resistant and clindamycin susceptible in vitro and in the condition that they are not place adjacent to each other . in these cases , in vivo treatment with clindamycin may lead to clinical therapeutic failures ( 4 , 5 ) .\nthe aim of this study was to determine the incidence of inducible clindamycin resistance in s. aureus isolates collected from clinical specimens in this geographic area .\ntotally 162 s. aureus isolates were collected from clinical specimens of patients admitted to three university hospitals with 462 , 420 and 300 bed capacities in kerman , south - east of iran , from march 2011 to february 2012 .\nconfirmation of s. aureus isolates and detection of methicillin resistant s. aureus ( mrsa ) were performed by phenotypic and genotypic methods as previously described ( 6 ) . only one isolate per patient\nthis test was performed by placing an erythromycin ( 15 g ) disk ( mast , group ltd .\n, merseyside , uk ) at a distance of 15 to 20 mm from clindamycin ( 2 g ) disk ( mast , group ltd . ,\nmerseyside , uk ) on a mueller - hinton agar plate inoculated with 0.5 mcfarland standard bacterial suspensions . following overnight incubation at 37c , flattening of the clindamycin zone adjacent to the erythromycin disk ( d shaped ) indicated inducible clindamycin resistance ( 7 ) .\nfrom 162 s. aureus isolates tested for determination of inducible clindamycin resistance , 70 ( 43.2% ) were mssa and 92 ( 56.8% ) isolates were mrsa ( table 1 ) .\nsensitivity to both erythromycin and clindamycin was significantly higher in mrsa compared to mssa isolates .\nresistance to methicillin , erythromycin and clindamycin was observed in 92 ( 56.8% ) , 75 ( 46.29% ) and 46 ( 28.4% ) of the isolates , respectively .\ninducible resistance to clindamycin was determined in 14 ( 8.64% ) isolates ( d - test positive , figure 1 ) .\ntable 2 shows the distribution of d - test positive s. aureus isolates in clinical specimens . among those , 11 ( 78.57% )\nabbreviations : mssa , methicillin susceptible s. aureus ; mrsa , methicillin resistant s. aureus ; ery , erythromycin ; cli , clindamycin ; s , sensitive , r , resistant ; cmlsb , constitutive macrolide lincosamide and streptogramin b ; imlsb , inducible macrolide lincosamide and streptogramin b. data are presented as no . ( % ) .\nflattening of the clindamycin zone adjacent to the erythromycin disk produces a d shape . \n( % ) . including : blood , skin and soft tissue , cerebrospinal fluid .\nclindamycin is an effective antibiotic agent used in the treatment of skin and soft - tissue infections caused by s. aureus isolates .\nthis antibiotic has good tissue penetration , potential antitoxin effects , and also accumulates in abscesses ( 8) .\nhowever , resistance to clindamycin may develop in s. aureus isolates with inducible phenotype and these isolates have a high rate of spontaneous mutation which would enable these isolates to develop constitutive resistance to clindamycin during therapeutic process ( 4 ) . a positive\nd - test indicates the existence of inducible resistance to clindamycin . in this study 8.64% of 162\ns. aureus isolates were d - test positive that is comparable with the findings of the studies by rahbar and hajia ( 9.7% ) ( 9 ) and sedighi et al .\nthe prevalence of inducible and constitutive clindamycin resistance differs in different geographic areas ( 12 ) . in our study\nhigh number ( 46.29% ) of s. aureus isolates were resistant to erythromycin . among those , 14 ( 18.66% ) isolates had positive and 15 ( 20% ) had negative d - test results and 46 ( 61.33% ) were constitutive clindamycin resistance . in this study the prevalence of inducible and constitutive resistance to clindamycin in mrsa ( 11.95% and 47.8% respectively ) is higher than those in mssa ( 4.28% and 2.85% , respectively ) .\nthe results of this study revealed that inducible resistance to clindamycin in s. aureus isolates is relatively high in this region .\ntherefore , d - test should be performed to prevent treatment failures of s. aureus infections caused by the agents that are resistant to erythromycin and sensitive to clindamycin .", "answer": "background : clindamycin is a frequently used antimicrobial therapeutic medicine used for the treatment of skin and soft tissue infections caused by staphylococcus aureus strains . resistance to this antibiotic is either constitutive or inducible . \n constitutive resistance to clindamycin could be detected by standard susceptibility testing methods . \n inducible clindamycin resistance could not be detected by in vitro routine tests . \n this type of resistance can be identified by d-test.objectives:the outbreak of inducible resistance to clindamycin in methicillin resistant and - susceptible s. aureus isolates were investigated in this study.materials and methods : totally 162 s. aureus isolates were evaluated for inducible clindamycin resistance by d - test in accordance with clinical and laboratory standards institute ( clsi ) guidelines.results:inducible clindamycin resistance was detected in 8.64% of s. aureus isolates . \n inducible and constitutive resistance to clindamycin was found to be higher in methicillin resistant s. aureus ( 11.95% and 47.8% respectively ) compared to methicillin susceptible s. aureus ( 4.28% and 2.85% respectively ) isolates.conclusions:our results showed that inducible resistance to clindamycin in s. aureus isolates is relatively higher in this region . \n therefore , d - test should be performed to prevent treatment failures against infections caused by s. aureus , which are resistant to erythromycin and the sensitive ones against clindamycin .", "id": 181} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nover the past few decades , the advancement in breast screening and management has increased the overall survival in women with breast cancer . but\nthis in turn , exposes them to the risk of developing new primary malignancies or metastases .\nthe metastatic involvement of gastrointestinal ( gi ) tract is rare and that of the rectum even rarer . even though lobular carcinoma constitutes only 10% of breast cancers , it is the commonest breast cancer metastasizing to the colon and rectum ( 1 ) .\nthese metastatic lesions can lead to diagnostic challenge for clinicians as they can mimic primary colo - rectal cancer due to the lack of diagnostic signs .\nwe report a rather unusual case of metastatic invasive ductal carcinoma masquerading as primary rectal cancer .\na 60 year old woman presented with a suspicious lump in her left breast in early 1996 and underwent open diagnostic surgical excision . she was found to have a moderately differentiated invasive ductal carcinoma measuring up to 20 mm in its greatest diameter extending less than 1 mm from the diagnostic excision margin . subsequently , she underwent left mastectomy and axillary node clearance which failed to show any residual invasive cancer . however , there was residual high grade cribriform dcis present adjacent to the diagnostic surgical excision cavity in the mastectomy specimen .\nthere was no evidence of vascular invasion and none of the seven lymph nodes excised contained any metastatic carcinoma [ g2t1n0mx ] .\nsince her cancer was oestrogen receptor ( er ) positive , she was started on tamoxifen post - operatively .\nshe presented 2 years later with localised pain in her right knee and bone scan revealed an isolated bony metastasis in the right proximal tibia .\nthis was managed using palliative radiotherapy to control the symptoms and her adjuvant hormonal therapy was switched to anastrazole ( astrazeneca plc , london , united kingdom ) .\nshe neither developed any loco - regional recurrence nor had any progression of her metastatic disease for the next 9 years . during this period\n, she underwent annual mammographic and clinical follow - up with her adjuvant hormonal treatment being stopped in 2005 after clinical consultation . in early 2007 , she presented with ongoing history of fresh rectal bleeding , alternating bowel habit and mucus discharge per rectum .\nabdomen was soft , non - tender without any organomegaly and digital rectal examination revealed a palpable tumour at 6 o'clock position .\nfungating rectal tumour on colonoscopy she underwent colonoscopy , which revealed a fungating tumour at 10 cm from the anal verge in the rectum and rest of the colon was normal ( figure 1 ) .\nthe histopathological examination of the biopsy revealed a poorly differentiated invasive adenocarcinoma ( figure 2 ) .\ntumour overlying the large bowel mucosa with the line demarcating the tumour edge with arrow pointing at the body of the tumour ( magnification4 ) .\nconsidering her previous history of invasive breast cancer , pathologist performed immunohistochemistry of the colonic biopsies .\nthe tumour cells were strongly positive for cytokeratin ( ck ) 7 with focal positivity for er but were negative for both carcino embryonic antigen ( cea ) and ck 20 .\nthe above immunohistochemistry profile with previous history of breast cancer favoured a metastatic breast origin over a primary colonic cancer even though the clinical and colonoscopic findings were not typical .\nthe staging ct scan did nt show any evidence of metastasis and the mri scan revealed a locally advanced tumour with involvement of mesorectal facial margins with possible involvement of the peritoneum locally ( figure 3 ) . the bone scan failed to reveal any evidence of active metastatic disease . mri scan .\narrow pointing to the localized tumour in the rectum with no evidence of widespread metastasis after discussing in the multi - disciplinary team meeting ( mdt ) , it was decided to treat the tumour with a short course of pre - operative radiotherapy .\nthe histopathological examination of the resected tumour showed poorly differentiated metastatic adenocarcinoma with predominantly solid , but with focal glandular growth pattern and large areas of necrosis .\nthe tumour involved full thickness of the bowel but the serosal surface and the resection margins were free of cancer .\nthere was no evidence of metastatic cancer in any of the twenty two lymph nodes excised .\nimmunohistochemistry showed tumour cells to be negative for cea and ck 20 , but was strongly positive for ck7 ( figure 4 & 5 ) .\nthe tumour also showed focal positivity for er and was negative for both progesterone receptor ( pr ) and human epidermal growth factor receptor 2 ( her2 ) . after comparing the morphological and immunohistochemistry charachteristics of the primary breast cancer and rectal tumour\n, the pathologist concluded that the features were consistent with a primary breast cancer metastasising to the rectum .\nshe underwent an uneventful post - operative recovery and remains disease free during her follow - up until now .\nck 20 immunohistochemistry positive normal large bowel mucosa with the adenocarcinoma being negative ( magnification 4 ) .\nin the largest clinical series till date , only < 1% ( 17 out of 2604 patients followed over 18 years ) of the patients with breast cancer were found to have gastro - intestinal [ gi ] metastasis ( 2 ) .\ninformation gathered from autopsy series shows small intestine being the commonest site of metastasis ( 28% ) followed by oesophagus ( 25% ) , stomach ( 25% ) , colon ( 19% ) and rectum ( 4% ) .\nthe commonest route of metastasis to the gi tract is through the haematogenous route followed by lymphatic and peritoneal spread .\neven though there are a few case reports of lobular carcinoma metastasizing to the rectum , there are only 3 case reports in the literature of invasive ductal carcinoma metastasizing to the rectum till date ( 3 - 5 ) . as a clinician the main challenge lies in the differentiation of such metastatic lesions from primary colo - rectal cancer as\nthe clinical presentation of metastatic lesion can be non - specific and mimic a primary cancer as in the present case .\nthe radiological investigations like , ct scan and double contrast barium enema are helpful in localizing the lesion but can not differentiate between them .\non endoscopy , the colo - rectal metastasis appear as diffuse thickening of the colonic wall mimicking linitis plastica or like in crohn s disease with ulcerated or nodular areas rather than as a solitary , discrete mass seen in primary colonic lesion ( 1 ) .\nbut the differentiation was made more challenging in our case , as colonoscopy revealed a solitary fungating mass arising from the rectal mucosa mimicking a primary rectal cancer .\nhistopathological examination by itself may not be conclusive as the tumour invasion is primarily in the sub - serosa , so unless deep endoscopic biopsies are available the diagnosis will be made only after resection of the tumour .\nbut immunohistochemical markers such as er , pr , gross cystic disease fluid protein ( gcdfp-15 ) , and differential expression of ck7 and ck20 can facilitate an accurate diagnosis as seen in the present report .\nsystemic treatment with chemotherapy and/or hormonal therapy is usually employed in patients with confirmed diagnosis of gastrointestinal metastasis ( 1 ) .\nthe role of surgery is limited to palliation or in patients presenting acutely with obstruction or perforation of the hollow viscus .\nthe lack of concordance between the clinical , radiological and colonoscopic findings with that of the histological findings resulted in our patient being managed with pre - operative radiotherapy followed with low anterior resection .\nthe prognosis of gi metastasis from primary breast cancer is poor with few patients surviving beyond two years , although survival up to nine years has been reported .\nour patient remains well and disease free four years after treatment for her rectal metastasis .\ngiven the increased survival of breast cancer patients due to the early diagnosis through breast screening and better management with current therapeutic regimens , more unusual presentations of metastatic disease , including involvement of the gastrointestinal tract should be anticipated .\nso the recognition of this rare entity ( rectal metastasis from primary breast cancer ) is important , as presentation resembles that of primary rectal carcinoma and differentiation is vital as different therapeutic modalities may be appropriate .", "answer": "gastrointestinal metastasis of the breast cancer is rare and its management varies significantly from that of a primary bowel cancer . \n we report a case of invasive ductal cancer metastasizing to the rectum and masquerading as a rectal primary.a 60 year old caucasian woman presented with fresh rectal bleeding nine years after treatment of her primary breast cancer . \n the investigations revealed features suggestive of primary rectal malignancy and was managed accordingly . \n however , the surgical histopathology revealed poorly differentiated metastatic adenocarcinoma and the immunohistochemical evaluation confirmed origin from a breast primary . \n she had an uneventful post - operative recovery and remains disease free thus far.the continuing advancement in the management of breast cancer patients with resulting increase in the overall survival will lead to such unusual metastatic presentations . \n hence , the awareness , identification and differentiation of such rare metastatic presentation are important in order to manage the patients appropriately in the future .", "id": 182} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients with univentricular heart malformations are at increased risk of suffering from thromboembolic events ( te ) . at least 20% of patients with univentricular hearts have reported to experience te , of which 25% are fatal . despite the high incidence of te , no consensus has been reached regarding the role of long - term anti - thrombotic treatment in this group of patients . here ,\nwe present a case of a 19-year - old woman with a univentricular heart who suffered a major stroke .\na 19-year - old woman born with a univentricular heart was found unconscious in her bed in the morning .\nshe was respiratory and circulatory stable with no fever at admission to the local hospital .\nthe glasgow coma scale score was 5 ( eyes , 1 ; verbal , 1 ; motor , 3 ) .\nan electrocardiogram showed sinus rhythm , left axis deviation , and left - sided hypertrophy , but was otherwise normal .\na test of arterial blood gasses revealed a fully compensated metabolic acidosis with ph 7.37 ( normal range 7.377.45 ) and base excess 7.7 mm ( 3.0 to 3.0 mm ) .\nvenous blood tests showed raised plasma lactate 3.7 mm ( 0.72.1 mm ) , plasma myoglobin 280 g / l ( 1949\ng / l ) , plasma glucose 8.6 mm ( 4.27.2 mm ) , plasma fibrin d - dimer 1.0 mg / l ( 0.00.5 mg / l ) , and inr 1.5 ( < 1.2 ) , whereas the remaining standard tests were all normal , including hemoglobin , leucocyte differential count , electrolytes , c reactive protein , liver and pancreas enzymes , renal parameters , plasma ethanol , plasma paracetamol , and plasma salicylate .\nshortly after admission , the patient developed babinski reflexes and a pronounced decorticate posture with spontaneous flexion of the arms over the chest and extended legs with feet turned inward .\nafter a tracheal tube was inserted and assisted ventilation was initiated , the patient was transferred to the neurological intensive care unit at a tertiary hospital .\na repeated computed tomography scan and magnetic resonance imaging of the head were performed , as well as a computed tomography angiography of the head and the neck .\nthese scans unveiled a major stroke located in the left cerebral ( figure 1 ) and cerebellar hemispheres , corresponding to the areas supplied by the left middle and posterior cerebral arteries and the left superior cerebellar artery .\na segmental occlusion in the top of the basilar artery was identified ( figure 3 ) .\nfinally , a transthoracic echocardiography was performed , revealing a well - functioning univentricular heart with no detectable thrombi .\nwarfarin was prescribed and the patient gradually regained consciousness . however , a severe right - sided hemiparesis persisted and the patient was transferred to a local neurorehabilitation unit .\nlater , a magnetic resonance imaging scan of the thorax and upper abdomen was performed ( figure 4 ) .\nthe patient had been referred to a cardiologist at the age of 5 months due to shortness of breath and failure to thrive .\ncardiac ultrasound and catheterization had revealed a double inlet left ventricle ( figure 5 ) and a hypoplastic right ventricle without transposition of the great arteries .\nsymptoms were caused by heart failure due to high pulmonary flow , which was treated by pulmonary artery banding . at the age of 6 years , a total cavopulmonary connection ( tcpc ) , including a lateral tunnel with fenestration to the right atrium , was established .\nthe surgical procedure markedly improved the patient s well - being , and , at the age of 13 years , the fenestration was closed .\nlife - long prophylactic antithrombotic treatment with salicylic acid was prescribed . during the last surgical intervention ,\nthe patient suffered mild brain damage and was now described as behaving at the level of a 12-year - old .\npostoperative echocardiography revealed good systolic function of the left ventricle and mild right atrioventricular valve regurgitation .\nsince no cardiac thrombi were identified , it is not known whether the described stroke was caused by a cardiac - derived embolus or spontaneous cranial thrombi .\nspontaneous thrombi in 19-year old patients are , however , extremely rare . hence , seen in the light of a known cardiac malformation , the probability of a cardiac - derived cerebral embolus is very high .\nthe incidence of univentricular hearts is reported to be between 0.5 and three cases per 10,000 live births.1 today , patients with univentricular heart conditions are usually treated surgically with a three - stage tcpc / fontan procedure,2 which separates the systemic and pulmonary venous return a precondition for adequate oxygenation of the arterial blood entering systemic circulation .\nthe technique has evolved from the classic fontan3 ( right atrium - to - pulmonary artery connection ) through an intracardiac lateral tunnel procedure , and it is currently performed in many centers as an extracardiac tunnel procedure by insertion of a tube graft between the inferior vena cava and the pulmonary artery.4 te , both systemic venous and arterial , are a major cause of early and late mortality in tcpc patients .\nthe reported incidence of te in these patients varies from 3% to 25% , depending on study design , imaging technique , and follow - up period duration .\nstudies with longer follow - up periods and more sensitive imaging studies suggest an incidence of at least 20% , of which the mortality rate is 25%.59 asymptomatic pulmonary emboli have been detected in 16% of tcpc patients .\nalthough the etiology for the high risk of te is not well defined , possible explanations include abnormal blood flow in the univentricle , arrhythmias , venostasis , dehydration , protein - losing enteropathy , and coagulation abnormalities .\nno stratification of te risk has been made between the different types of surgical intervention .\nsuch data would be very useful and should be compared against the efficacy of each treatment .\nprocoagulant factors ( factors ii , v , vii , ix , and x ; plasminogen ; and fibrinogen ) and anticoagulant factors ( protein c and antithrombin iii ) are lower than normal controls prior to stage two or three of tcpc completion.10,11 increased platelet reactivity prior to tcpc completion has also been shown . a recent report , however , found no significant differences in thromboelastography ( a global whole - blood assay of coagulation ) in pediatric tcpc patients compared with healthy children.12 despite the high incidence of te , no consensus has been reached about the role of long - term antiplatelet or anticoagulation therapy in those patients who remain in stable sinus rhythm .\nsome studies advise against routine anticoagulation,13 whereas others recommend routine antiplatelet14 or anticoagulation therapy.15,16 one recent study suggests that antiplatelet and anticoagulation therapy are equally effective in preventing te.17 te reduce quality of life18 and cause sudden death19 in adult patients with fontan circulation .\ntherefore , in these patients , the benefit of long - term prophylactic antiplatelet or anticoagulation therapy must be carefully considered and weighed against the risk of detrimental hemorrhagic side effects .\ndisagreement about antithrombotic therapy in tcpc patients warrants future study that compares the different therapeutic strategies .\nfuture studies should most likely be observational case - control studies due to the practical and ethical problems associated with randomized controlled trials .\nthe need for such studies is emphasized by the presented case , which might suggest that more aggressive antithrombotic strategies should be routinely introduced .", "answer": "patients with univentricular heart malformations are at increased risk of suffering from thromboembolic events . \n we present a case of a 19-year - old woman born with a univentricular heart who suffered a major stroke while being treated with only salicylic acid . \n at least 20% of patients with univentricular hearts have been reported to experience thromboembolic events , of which 25% are fatal . despite the high incidence of thromboembolic events \n , no consensus has been reached regarding the role of long - term anti - thrombotic treatment in this group of patients . \n this lack of consensus warrants future studies that compare the different therapeutic strategies .", "id": 183} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit presents with various obstructive and irritative lower urinary tract symptoms ( luts ) like frequency , urgency , nocturia , intermittency , weak urinary stream etc .\nthe international prostate symptom score ( ipss ) is a tool which is very commonly used in the evaluation of the severity of symptoms of the patients .\nit is a self - administered questionnaire which scores the symptoms the patient has experienced over of the preceeding 4 weeks .\nit helps the clinician understand the severity of patient 's symptoms and can guide treatment .\nhence the responses can depend upon the level of education and understanding of the patient .\nthis can have a significant bearing on the ultimate score and can lead to improper selection of treatment .\nit can lead to significant distress both to the patient and to the treating physician due to the lack of optimum response by the treatment based on the ipss .\nthe ipss questionnaire has been translated and validated in various languages but it has not been validated in any of the indian languages .\nwe commonly employ the english version of the questionnaire . for a population that does not have english as its primary language\n, this issue may have a serious impact on the understanding of questions and the scoring . in this study\n, we evaluate the patient 's ability to understand the ipss by comparing the scores when the questionnaire was self - administered versus when it was administered using the assistance of a clinician .\npatients who presented with luts suggestive of bph , those who had passed at least twelfth grade school and had a reasonable command over english ( assessed by their ability to have a conversation in english with the clinician ) were included in the study .\nthose who had previously filled an ipss questionnaire or those who were < 40 years of age were excluded from the study .\nthe patients were first given the ipss questionnaire and were allowed to self - administer it .\nthe score sheet was taken away and then a blinded clinician ( 2 year resident in urology ) , who was not aware of the score on the self administered questionnaire , assisted the patient in filling the responses ( english version ) by interpreting and explaining the meaning of the questions in english .\nthe second questionnaire was administered on the same day , 4 - 5 hours after the administration of the first questionnaire .\nthe ipss questionnaire comprises of eight questions , seven regarding the symptoms over a period of the preceedinglast 1 month and one assessing the quality - of - life .\nthe seven questions assessing the symptoms include incomplete emptying , frequency , intermittency , urgency , weak stream , straining and nocturia .\neach of these symptoms is assigned a score from 0 to 5 for a maximum 35 points .\nthe scores of these seven questions are added to determine the severity of patient urinary symptoms as follows , mild - 0 - 7 , moderate - 8 - 19 and severe - 20 - 35 .\nthe eighth question assesses the quality of life is assigned a score of 0 - 6 . for each question ,\nthe score in both the questionnaires was noted and kappa agreement statistical test was used to assess the level of agreement between them . by convention , a kappa of 0.0 means that the agreement is no better than a chance event .\nkappa scores of 0.01 - 0.20 , 0.21 - 0.40 , 0.41 - 0.60 , 0.61 - 0.80 and 0.81 - 0.99 are interpreted as showing poor , fair , moderate , substantial and almost perfect agreement , respectively .\nthe kappa values of the scores for each question have been shown in table 1 . no question had a perfect agreement of scores in the self - administered and the clinician assisted scoring scenarios . only the scores of questions about weak stream and nocturia showed moderate \nthe overall mean scores , kappa value and its interpretation for each question of the ipss questionnaire the total scores for each patient were calculated for both the clinical scenarios and they were classified into mild , moderate and severe categories as per the criteria mentioned before .\nit was found that total scores in the self - administered and the clinician assisted scoring agreed poorly with each other as the kappa value was 0.19 .\nthe categorization of patient 's symptoms as per the ipss questionnaire when it was self - administered compared to when it was administered by an assessor\nipss questionnaire is recommended by the american urological association during the work up of a patient with luts . apart from helping the clinician in assessing the severity of the symptoms of a patient\n, it also acts as a guide in selecting the appropriate mode of treatment which can vary from watchful waiting to surgery .\nstudies in the western population have pointed out that there can be significant misinterpretation of the ipss by the patients .\nsome of these studies have shown that it depends upon the level of education , with patients having a low level of education showing marked misinterpretation .\nthe issue of non - availability of the questionnaire in a local language and its impact on the ability of a patient to self - administer a questionnaire in english has been highlighted by ogwuche et al .\nwe also believe that a validated ipss questionnaire in an indian language may be helpful in decreasing the error in interpretation , but additional studies will be needed to prove this .\nit has also been reported that the error in interpretation of the ipss questionnaire can lead to miscategorization of the patients symptoms and selection of a treatment that may not be effective for him .\nfor example , a patient who on self - administered ipss questionnaire has a score of 6 ( mild symptoms ) may be offered only watchful waiting while he actually may be having moderate or severe symptoms which becomes evident when the questionnaire is explained to him by a medical assistant .\njohnson et al . have pointed out that 25% of patients who self - reported a mild score on ipss actually had a moderate or severe score . in our study too , there was a misinterpretation of the ipss questionnaire by the patients .\nthe scores for each question showed a poor agreement for five out of seven questions .\nthere was also significant miscategorization of patients symptoms ( mild / moderate / severe ) when the scores on self - administered questionnaire were compared to the clinician assisted questionnaire .\nthus it is important to realize that although ipss questionnaire is an important tool in the work up of patients with luts , it should not be the sole guide for the treatment offered .\nour study shows that there are some questions that are more prone for misinterpretation by the patients hence assistance by a clinician may be desirable .\nwe administered the questionnaire on the same day which might have an effect on the results as the patients might have been able to recall their responses in the first questionnaire .\nthe second issue is that we did not stratify our results according to the level of education of the patients included in the study .\nit is possible that people with a higher education may have a lesser chance of misinterpretation of the questions .\nour results show that our patients , who do not have english as their primary language , misinterpret the ipss questionnaire .\nthere are significant differences in the symptom scores when the ipss is self - administered as compared to the assisted scoring .\nthis problem can lead to errors in interpretation of the symptom severity of patients by the health care providers ; may affect the choice of treatment and ultimately , the clinical outcome .", "answer": "introduction : the international prostate symptom score ( ipss ) is commonly used in the evaluation of the severity of symptoms of patients with prostatic enlargement . \n it is a self - administered questionnaire . \n it has not been validated in any indian language and an english version is used which can be difficult to interpret by our patients who do not have english as their primary language . in this study , we evaluate the patient 's ability to understand the ipss by comparing the scores when the ipss questionnaire was self - administered versus when it was administered using the assistance of a clinician.materials and methods : patients who presented with lower urinary tract symptoms suggestive of benign prostatic hyperplasia , who had passed at least twelfth grade of school and had a reasonable command over english were included in the study . \n they were allowed to self - administer the ipss questionnaire following which a clinician , blinded to these scores , assisted the patient in filling the questionnaire . for each question , \n the score in both the questionnaires was noted and kappa agreement statistical test was used to assess the agreement between the two scores.results:a total of 87 patients were included in the study . it was found that none of the questions had a perfect agreement of scores in the self - administered and \n the assisted administration.conclusion:our results show that our patients misinterpret the ipss questionnaire . \n this problem can lead to significant errors in interpretation of the symptom severity .", "id": 184} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiabetes is a metabolic disease that leads to high blood sugar due to either insulin insufficiency , insulin resistance or both .\naccording to the world health organization at least 171 million people ( 2.8% of the world population ) suffered from diabetes in year 2000 .\nit is expected that more than 70% of total diabetic patients in the world will be from developing countries by year 2030 .\nthe prevalence of type 2 diabetes in iran ranges from 1.3% to 14.5% which will increase as the population ages in both males ( 10.6% ) and females ( 11.3% ) .\nvascular diseases are one of the most common causes of morbidity and mortality in diabetic patients .\nalthough , there is positive relation between insulin resistance and vascular disease , the exact mechanisms by which diabetes leads to arthrosclerosis is not well- understood .\nc - reactive protein ( crp ) and interleukin 6 ( il-6 ) the two most sensitive markers of inflammation have been elevated in patients with type 2 diabetes . in addition , high crp level is shown to be a risk factor for developing type 2 diabetes , which may be atherogenic .\noxidative stress is a component of cellular damage and has an important role in the pathogenesis of a number of human diseases including atherosclerosis .\nmechanisms that contribute to increased oxidative stress in diabetes may include not only increased non - enzymatic glycosylation and auto - oxidative glycosylation but also to decreasing antioxidant defence potential .\nfao / who , define probiotics as live microorganisms which when administered in adequate amounts confer a health benefit on the host .\nlactic acid bacteria ( lab ) and bifidobacteria are the most common types of microbes used as probiotics .\nanimal studies showed that lactobacillus gg treatment not only reduces glucose intolerance but also significantly decrease hyperglycemia in streptozotocin induced diabetes rats . among other beneficial effects of probiotics and prebiotics ,\nlactobacilli and bifidobacteria are the primary probiotic bacteria which are associated with cholesterol reduction , although comparable effect may be produced by other lactic acid bacteria , such as enterococci .\nit has also been reported that oral administration of heat killed lactobacillus casei to non - obese diabetic ( nod ) mice reduces the incidence of diabetes , but the mechanism underlying this effect has not been clarified .\nthis study was designed to determine the effect of probiotics on lipid profile , glycemic control , insulin level , oxidative stress and inflammatory markers in patients with type 2 diabetes .\nthis single - blinded clinical trial comprised 40 patients with type 2 diabetes recruited from medical clinic affiliated with shiraz university of medical sciences ( sums ) shiraz iran .\ndiabetic patients with fasting blood glucose 126 mg / dl , aged from 25 to 65 years , and diagnosed as having diabetes for less than 15 years were eligible for the study .\nexclusion criteria were current smokers , subjects on non - steroidal anti - inflammatory drugs and multivitamin , as well as patients undergoing hormone replacement therapy , and those with any chronic diseases involving kidney , liver , and lung .\nthe research was approved by the ethics committee of sums , and written informed consent was obtained from all patients prior to commencement of the study .\nsubjects were initially studied during a screening visit after an overnight fast starting from 8 pm in previous evening baseline plasma samples were collected and analyzed for triglyceride , total cholesterol , ldl - c , hdl - c , glucose , insulin , malondialdehyde , hs - crp and il-6 . using balanced block random sampling , subjects were then divided into two groups of intervention ( probiotics ) and placebo .\npatients in the intervention or treatment group received 1500 mg probiotic capsules twice daily , after lunch and evening meal for 6 weeks .\nthe lactobacillus probiotics contained l. acidophilus , l. bulgaricus , l. bifidum , and l. casei .\npatients in placebo group received 1500 mg capsules containing 1000 mg magnesium stearate twice daily for six weeks .\nmagnesium stearate is generally considered safe for human consumption at levels below 2500 mg / kg per day . according to the fda s subcommittee report on gras ( generally recognized as safe ) substances ( scogs ) , adding magnesium stearate directly to human food\nafter six weeks of experiment , fasting blood samples were collected and analyzed for all aforementioned parameters . \n\nmethods of data gathering \n demographic data including age , sex , weight , height , body mass index ( bmi ) , and waist to hip ratio ( whr ) were measured before and after the intervention .\nauto - analyzer bio - systems a-25 was used to determine the lipid profile and blood glucose concentration .\nelisa method was employed to determine insulin levels , high sensitive crp ( hscrp ) and il-6 .\ncomparison between different groups was performed through two independent samples t - test . in the absence of normal distribution , comparison between groups\nwas made using non - parametric wilcoxon on signed ranks and mann - whitney tests .\nthe study was conducted on 34 patients , of which 26 were females and 8 males .\nthere were no significant differences in bmi and whr between placebo and treatment groups ( table 1 ) . \nthe mean anthropometric data in the placebo and treatment groups * standard deviation ; * * waist to hip ratio ; * * * body mass index \n table 2 shows changes in biochemical markers after probiotic treatment . the fasting blood sugar did not change significantly after probiotic treatment ( table2 ) .\nserum triglyceride concentration was reduced in probiotic treated group but the change was not significant ( table2 ) .\nthere were no significant differences in total serum cholesterol , ldl - c , and hdl - c levels , between probiotic and placebo groups ( table2 ) . fasting plasma insulin level did not change in probiotic group compared to placebo group ( table2 ) . the mean parameters in placebo and treatment groups * non - parametric wilcoxon on signed ranks test ; insulin - sensitivity measure : quicki ( quantitative insulin sensitivity check index ) : 1/log ( glucose0 ( mg / dl))+log ( insulin0 ( mu / ml ) ) ; insulin - resistance measures : homa ir ( homeostasis model for insulin resistance ) : insulin0(mu / ml)glucose0 ( mmol / l)/22.5 , firi ( fasting insulin - resistance index ) : insulin0 ( mu / ml)glucose0 ( mmol / l)/25 , bennetts index : 1/log ( glucose0 ( mmol / l))log ( insulin0 ( mu / ml ) ) , insulin / glucose : insulin0 ( mu / ml)-to - glucose0 ( mmol / l ) ratio although mda and il-6 levels were reduced in treatment group , but the changes were not statistically significant ( table 2 ) .\nthere were an increase in crp levels in treatment group compared to placebo , but the change was not significant ( table2 ) .\ninsulin - sensitivity was determined through quantitative insulin sensitivity check index ( quicki ) and insulin - resistance by homa ir , firi , bennett s index and ins / gluc ratio but there were no significant changes in these indices ( table 2 ) .\ndiabetic complication , such as cardiovascular disease on the one hand and the dramatic growth of diabetic incidence on the other , demands a natural and safe solution to control and delay these complications .\na strong association has been found between the level of oxidative stress and risk of cardiovascular disease .\noxidative stress not only causes much pathopysiological complication but is also linked to insulin resistance which in turn causes diminished glucose uptake and disposal in peripheral tissues , and increasing glucose production in the liver .\nit has also been reported that postprandial hyperlipidemia and hyperglycemia are associated with increasing ldl - c oxidation and higher risk for cardiovascular disease .\nstudies showed that probiotic containing foods may reduce the concentration of serum lipid and decreases both fasting and postprandial blood sugars in human .\nmann and spoerry reported that lactic acid bacteria are associated with a marked reduction in the total serum cholesterol .\nyun si et al , reported a significant reduction in fasting and postprandial glucose and decreasing hba1c in probiotic ( bnr17 ) treated rats . in the present study ,\nwe were not able to demonstrate any significant effect on fasting blood glucose after treating with probiotics . serum triglyceride concentration was decreased but the change was not statistically significant .\nthe reasons for these unexpected results can be related to either the small sample size or short duration of the study . \nobserved some strains of lactobacillus acidophilus may decrease cholesterol absorption by enhancing the binding of cholesterol to the intestinal lumen .\nother possible cholesterol lowering properties of probiotics are deconjugation of bile by bile salt hydrolyses , binding of cholesterol to cellular surface and coprecipitation of cholesterol with deconjugated bile .\nthis study showed no significant improvement in serum total cholesterol , ldl - cholesterol and or hdl - cholesterol after treating diabetic patients with probiotics .\nyadav et al . in their study on diabetic rats reported a marked reduction in pancreatic tissue oxidative damage due to a significant decrease in lipid peroxidation . in another study the same investigators showed that probiotic dahi not only decreases oxidative damage but also increases the antioxidant content and activities of catalase , glutathione peroxidase and superoxide dismutase in diabetic rats .\nthe mechanism by which oxidative stress results in diabetic complications and tissue damage is the overproduction of the reactive oxygen species and reduction of the antioxidant defense function of the body .\nlipid peroxidation is one of the main biological targets of oxidative stress , which leads to formation of secondary products such as malondialdehyde that exacerbates oxidative damage .\nmda has been found to significantly increase in pathological conditions , which is considered as a common oxidative stress biomarker in recent years . \nthe present study , showed a reduction in mda levels in probiotic - treated group ; however , the reduction was not statistically significant .\n. showed a significant reduction in blood glucose and mda level in type 2 diabetic patients after consuming probiotic yogurt .\nevaluated the functional efficacy of antioxidative properties of probiotic in healthy subjects and found a significant improvement in blood total antioxidant activity ( taa ) and total antioxidant status ( tas ) after receiving probiotics .\nharisa et al . also reported a significant decrease in mda concentration after treating diabetic rats with l. acidophilus .\ndivergent evidence is available on the anti - inflammatory properties of probiotics . while some studies reported beneficial effect , others showed no effect at all . in this study , interleukin-6 ( il-6 )\nexamined the effect of probiotic bacteria on in vivo cytokine , antibody , and inflammatory responses in allergy - prone infants and showed that infants receiving probiotic had higher plasma levels of crp , and il-10 compared with those in the placebo group .\nstudied the effect of lactobacillus rhamnosus gg ( lgg ) on rheumatoid arthritis ( ra ) patients and reported an increase in serum il-1 beta after lgg treatment with no significant change in il-6 , tnf - alpha , myeloperoxidase ( mpo ) , and il-10 .\na reduction in oxidative stress and cardiovascular risk factor seems to be an ideal treatment strategy in type 2 diabetic patients .\nthe result of this study demonstrated that a 6 weeks oral treatment with probiotics decreased the concentration of tg , mda , and il-6 level in type 2 diabetic patients ; however the change were not statistically significant .\nthese finding could warrant future studies to determine the therapeutic effects of probiotic on diabetic patients .", "answer": "background : the dramatic increase in the incidence of diabetes and its associated complications require a natural and safe solution to control and delay such complications . \n the present study tested the hypothesis that probiotics may affect biochemical indices of diabetic patients \n methods : thirty four types 2 diabetic patients aged between 25 to 65 years , and diagnosed with diabetes for less than 15 years were selected for this single- blinded clinical trial . using balanced block random sampling , \n the patients were divided into two groups of intervention ( probiotics ) and placebo . \n blood samples tested for baseline glucose , insulin , tg , total cholesterol , ldl - c , hdl - c , malondialdehyde , high sensitive crp ( hs - crp ) and il-6 . \n after six weeks of experiment , fasting blood samples were re - tested and the data obtained were analyzed using spss software . \n \n results : there were no significant differences between anthropometric data including body mass index and waist to hip ratio in placebo and treatment groups . \n there was no significant difference in fbs , serum tg concentration total cholesterol and ldl - c levels between placebo and treatment groups . \n hdl - c levels were slightly elevated after probiotic treatment , which were not statistically significant . \n insulin , mda and il-6 levels were reduced and high sensitive crp hs.crp levels were elevated , although , not statistically significant . \n \n conclusion : the result of this study indicates a non- significant declining trend in the level of tg , mda and il-6 and insulin resistance after consumption of probiotics .", "id": 185} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntuberculosis of oral cavity is a rare entity . even before antitubercular chemotherapy era , oral lesions occurred less commonly in patients with pulmonary tuberculosis .\na 55-year - old labourer was referred to the outpatient department of our centre as a case of suspected gingivobu - ccal carcinoma for further evaluation and management .\nhe had a non - healing ulcer in the oral cavity for one and a half months , which was associated with pain .\nhe had been well until six weeks earlier when he noticed a lesion in his oral cavity .\nhe visited the local doctor for this and was given symptomatic treatment and vitamin supplements .\non enquiry , he had no systemic symptoms of chronic disease like fever , weight loss , and loss of appetite or weight .\nhe also had no history of tuberculosis or contact with a tuberculosis patient . on clinical examination ,\nthe patient had an ulcer in the right lower gingivobuccal sulcus of size about 21 cm and was covered with slough .\nthere was also mild fullness and soft tissue induration in the cheek below the lip .\nthe patient 's height was 167 cm ; weight , 62 kg ; blood pressure , 124/76 mm hg ; and pulse , 74 beats per minute .\non further investigation , haemoglobin was 13.9 gm% , total white blood cell count was 6,400 cells / dl , and erythrocyte sedimentation rate was 13 mm at the end of one hour .\nthese are usually accompanied by associated history like a stressor event or the presence of a sharp tooth , etc , pointing to diagnosis .\n. the most common cause of a non - healing ulcerative lesion in the oral cavity is malignancy .\nthe history is usually that of a rapidly growing lesion that does not respond well to any form of management . in most cases\nit is also usually accompanied by weight loss and features of chronic disease . in a developing country\nevery year , approximately 2.2 million people develop tuberculosis , of which about one million are new - smear positive highly infectious cases and about 5 lakh people die of tuberculosis every year .\nthis should be considered in the differential diagnosis , particularly in a non - healing lesion that does not respond to the usual therapy .\nactinomycosis is a rare , chronic , spreading , suppurative , granulomatous and fibrosing infection characterised by the formation of multiple abscess , draining sinuses and the release of characteristic sulphur granules .\npeak incidence occurs between 15 and 30 years , and males are more frequently infected than females .\nthe majority of examples of the clinical disease are cervicofacial ( 55% ) , with only 20% occurring in an abdo - minopelvic form and 15% as a thoracopulmonic form .\n. are anaerobic or aerotolerant ( facultatively anaerobic ) , non - sporulating , gram - positive bacteria that tend to form branching rods and filaments and have a fermentative type of carbohydrate metabolism .\nare not regarded as virulent human pathogens and are best considered as opportunistic pathogens , as they are normally present in healthy individuals as commensals of the mouth cavity and the upper respiratory tract .\ntheir presence in the oral and respiratory specimens does not necessarily signify clinical disease and might often not be reported .\nare polymicrobial . the copathogens are most commonly colonisers of the respective organ systems involved .\nthey act synergistically by inhibiting host - defense mechanisms or reducing the oxygen tension in the affected tissue , which promotes the growth of actinomyces spp .\nsyphilis is an infectious disease caused by a spirochete called treponema pallidum ( tp ) , which has a tropism for several organs and tissues in the body , causing complex clinical manifestations .\ntransmission of syphilis occurs mostly through sexual intercourse and sites of inoculations are usually genitals , though it can also be extragenital .\nit is characterised by several different dermatological lesions , involving both skin and mucous membrane . in the first stage of the disease ( primary syphilis ) , oral chancres\nsyphilitic chancre is a solitary , painless , indurated , hard in consistency , reddish ulcer , accompanied by regional lymphadenopathy , which is localised at the site of tp inoculation and usually resolves after approximately one month without scarring . in secondary syphilis ,\nthe oral manifestations are characteristic lesions , which are multiple mucous patches that are slightly raised and covered by grayish , white pseudomembranes and surrounded by erythema .\noral lesions are often painful and snail track ulcers result when multiple mucous patches become confluent .\nthe diagnosis is confirmed by the specific serology and the demonstration of tp in the lesion .\ntp has a slender , coiled morphology and when examined by dark - field microscopy , it was seen moving in a drifting rotary motion ( corkscrew ) .\nnaat is better than dark - field microscopic examination in the case of oral lesions because of the possible presence of saprophytic tp in the mouth .\nchest x - ray revealed an ill - defined patchy opacity and reticulo - nodular opacities in the upper and mid zone of both lungs [ figure 2 ] .\nsputum was positive for the presence of acid - fast bacilli 1 + in two consecutive samples .\nthese are usually accompanied by associated history like a stressor event or the presence of a sharp tooth , etc , pointing to diagnosis .\n. the most common cause of a non - healing ulcerative lesion in the oral cavity is malignancy .\nthe history is usually that of a rapidly growing lesion that does not respond well to any form of management . in most cases\nit is also usually accompanied by weight loss and features of chronic disease . in a developing country\nevery year , approximately 2.2 million people develop tuberculosis , of which about one million are new - smear positive highly infectious cases and about 5 lakh people die of tuberculosis every year .\nthis should be considered in the differential diagnosis , particularly in a non - healing lesion that does not respond to the usual therapy .\nactinomycosis is a rare , chronic , spreading , suppurative , granulomatous and fibrosing infection characterised by the formation of multiple abscess , draining sinuses and the release of characteristic sulphur granules .\npeak incidence occurs between 15 and 30 years , and males are more frequently infected than females .\nthe majority of examples of the clinical disease are cervicofacial ( 55% ) , with only 20% occurring in an abdo - minopelvic form and 15% as a thoracopulmonic form .\nare anaerobic or aerotolerant ( facultatively anaerobic ) , non - sporulating , gram - positive bacteria that tend to form branching rods and filaments and have a fermentative type of carbohydrate metabolism .\nare not regarded as virulent human pathogens and are best considered as opportunistic pathogens , as they are normally present in healthy individuals as commensals of the mouth cavity and the upper respiratory tract .\ntheir presence in the oral and respiratory specimens does not necessarily signify clinical disease and might often not be reported .\nthey act synergistically by inhibiting host - defense mechanisms or reducing the oxygen tension in the affected tissue , which promotes the growth of actinomyces spp .\nsyphilis is an infectious disease caused by a spirochete called treponema pallidum ( tp ) , which has a tropism for several organs and tissues in the body , causing complex clinical manifestations .\ntransmission of syphilis occurs mostly through sexual intercourse and sites of inoculations are usually genitals , though it can also be extragenital .\nit is characterised by several different dermatological lesions , involving both skin and mucous membrane . in the first stage of the disease ( primary syphilis ) , oral chancres\nsyphilitic chancre is a solitary , painless , indurated , hard in consistency , reddish ulcer , accompanied by regional lymphadenopathy , which is localised at the site of tp inoculation and usually resolves after approximately one month without scarring . in secondary syphilis ,\nthe oral manifestations are characteristic lesions , which are multiple mucous patches that are slightly raised and covered by grayish , white pseudomembranes and surrounded by erythema .\noral lesions are often painful and snail track ulcers result when multiple mucous patches become confluent .\nthe diagnosis is confirmed by the specific serology and the demonstration of tp in the lesion .\ntp has a slender , coiled morphology and when examined by dark - field microscopy , it was seen moving in a drifting rotary motion ( corkscrew ) .\nnaat is better than dark - field microscopic examination in the case of oral lesions because of the possible presence of saprophytic tp in the mouth .\nchest x - ray revealed an ill - defined patchy opacity and reticulo - nodular opacities in the upper and mid zone of both lungs [ figure 2 ] .\nsputum was positive for the presence of acid - fast bacilli 1 + in two consecutive samples .\nprimary tuberculosis of the oral cavity is rare , as it occurs in young individuals and is associated with cervical lymphadenopathy.[258 ] secondary tuberculosis of the oral cavity usually occurs following pulmonary tuberculosis .\nit is more common than the primary variety and occurs more often in old age.[257 ] tuberculosis of the oral cavity is rare because the intact mucosa is resistant to tuberculous infection and saliva has a protective effect .\nother possible causes for the relative rarity of oral tuberculosis include the presence of saprophytes in the oral cavity and resistance of stratified muscles to bacterial invasion .\nthere are reports in which dentists with pulmonary tuberculosis have infected patients during dental manipulation .\nnasolabial infection occurred in a physician who administered mouth - to - mouth resuscitation to a tuberculosis patient .\nother sites include the gingiva , soft palate , lip , buccal mucosa , floor of the mouth , and gingivobuccal sulcus . oral tuberculosis may present as single or multiple , painful or painless ulcers with irregular border .\nit can also present as nodules , fissures , vesicles , or peri - apical granulomas .\nthe oral tuberculous ulcers have some characteristic clinical features including chronicity , hyperemic changes , and multiple or satellite lesions , which lead to the suspicion of a tuberculous lesion .\noral tuberculosis occurs in 0.4 - 1.5% of patients with pulmonary tuberculosis . at present , with improved community health and anti - tubercular medication , the incidence of tuberculosis has decreased .\noral tuberculosis is not considered in the differential diagnosis of patients with oral ulcer by many clinicians ; hence , it is missed or the treatment is delayed .\nthe purpose of this paper is to alert clinicians to consider oral tuberculosis in patients with non - healing oral ulcer . on consultation with the physician ,\nanti - tubercular therapy was initiated with isoniazid ( 10 mg / kg of body weight ) , rifampicin ( 10 - 20 mg / kg of body weight ) , and pyrazinamide ( 10 - 20 mg / kg of body weight ) and ethambutol for two months , followed by isoniazid and rifampicin for the following four months . during the period , the patient was instructed not to undergo any surgical procedure within the oral cavity and was warned of transmitting the disease to others .\ntuberculous ulcer of the oral cavity secondary to pulmonary tuberculosis . from the department of head and neck oncology , tata memorial hospital , mumbai .", "answer": "tuberculosis of the oral cavity is a rare condition . \n a 55-year - old labourer was referred as a case of oral cancer for further management . \n the patient had no systemic symptoms . \n biopsy of the lesion revealed caseating granulomatous inflammation . \n chest x - ray and sputum revealed evidence of asymptomatic pulmonary tuberculosis . \n the purpose of this paper is to sensitize clinicians to consider oral tuberculosis as a differential diagnosis in patients with an non - healing oral cavity ulcer .", "id": 186} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen evaluating patients for clinical trial , intrauterine pregnancy is commonly considered an exclusion criteria , however guidelines do not exist to determine what to do should a pregnancy test result as positive .\nthe patient underwent standard - of - care therapy upfront with progression of disease and was referred to investigational therapeutics for phase i treatment .\npelvic ultrasound and -hcg heterophilic antibody testing were negative ruling out intrauterine and ectopic pregnancy or phantom hcg .\nher elevated -hcg appeared consistent with paraneoplastic syndrome reflected in a decline in -hcg that correlated with a response to treatment .\na 34-year - old african american female with metastatic mucinous ovarian carcinoma presented with a pelvic mass discovered during her annual gynecological examination .\nan ultrasound showed a 7.7 8.7 cm left ovarian mass with complex appearance .\nlaparoscopic left salpingo - oophorectomy showed a moderately differentiated mucinous ovarian carcinoma , stage ic1 , due to intraoperative rupture of the ovarian mass .\ntumor cells were diffusely positive for keratin 7 and very focally positive for keratin 20 .\nthe patient was taken for diagnostic laparoscopy with appendectomy , omentectomy , and multiple peritoneal biopsies by a gynecologic oncologist ; all of which were negative for malignancy .\neight weeks later the patient started adjuvant chemotherapy with one cycle of capecitabine and oxaliplatin ( xelox ) , transitioned to four months of fluorouracil and oxaliplatin ( folfox ) due to insurance issues .\nthe ct abdomen and pelvis post folfox chemotherapy showed an enhancing 2.6 cm nodule in rectus abdominis muscle .\nthe patient underwent an exploratory laparotomy with excision of a 5 6 cm abdominal mass involving fascia and muscle , consistent with metastatic adenocarcinoma .\nafter recovery , the patient received chemotherapy with carboplatin and paclitaxel for 6 months .\nthe ct abdomen and pelvis performed following 6 months of carboplatin and paclitaxel showed progression of disease with new nodal and perihepatic implants .\nthe patient subsequently consulted with the md anderson cancer center department of investigational cancer therapeutics for phase i clinical trial options .\nthe patient was treated with a phosphatidylinositol-4,5-bisphosphate 3-kinase ( pi3k ) inhibitor plus a mitogen / extracellular signal - regulated kinase ( mek ) inhibitor with progression of disease after 5 months .\nshe then started on a second phase i trial with a polymeric micellar nanoparticle of the substance dach - pt ( 1,2-diaminocyclohexane platinum ) , an in vivo metabolite of oxaliplatin , with progression following 1 cycle of therapy .\nthe patient was then enrolled in a trial with paclitaxel , bevacizumab and temsirolimus ( pat ) . on the day of clearance to start treatment , she was found to have a positive urine and serum pregnancy test .\nthe left ovary was surgically absent however the right ovary was enlarged with complex cystic mass with solid components measuring 9.5 6.6 cm .\nthe work - up for false positive elevation of -hcg including serial dilutions , incorporation of animal serum and outside institutional validation testing for -hcg heterophile antibody , was negative .\ntherefore , the -hcg elevation was not thought to be related to a phantom hcg .\ndilation and curettage to rule out trophoblastic disease was planned , but not completed due to discovery of a deep vein thrombosis and initiation of therapeutic anticoagulation .\nas no intrauterine or extrauterine pregnancy could be identified , after several weeks , the patient returned to clinic and was cleared to start treatment . at that time , her -hcg was 210.3 .\nthree weeks post treatment with pat , the -hcg decreased to 27.5 and ct scans showed partial response ( fig .\n, the patient was admitted to the intensive care unit for weakness due to guillain barre syndrome .\nnearly all female patients undergoing enrollment on clinical trial are evaluated for pregnancy as part of standard exclusion criteria .\nan elevated -hcg in the absence of viable pregnancy can occur for multiple reasons and has a broad differential diagnosis including miscarriage , ectopic pregnancy , pituitary hcg production , trophoblastic disease and phantom hcg .\nectopic pregnancy is frequently suspected when -hcg levels plateau or fail to double within 48 h without evidence of intrauterine pregnancy with ultrasound . when intrauterine and extrauterine pregnancy are ruled out ,\npituitary hcg may be produced in perimenopausal or postmenopausal women . as estrogen and progesterone production decreases , releasing gonadotropin releasing hormone ( gnrh ) from negative feedback , luteinizing hormone ( lh ) and follicular stimulating hormone ( fsh ) rise .\nthe subunit gene of lh is found in a sequence of 7 hcg subunit genes and therefore uncontrolled gnrh stimulation may lead to hcg production by pituitary gonadotrope cells ( cole , 2005 ) . using an fsh level of 45.0 miu\n/ ml identified hcg of perimenopausal women , ages 4155 years , with mildly increased serum hcg concentrations ( 5.014.0 miu / ml ) , an fsh cutoff of 45.0 miu / ml identified hcg of placental origin with 100% sensitivity and 75% specificity .\nfsh levels greater than 45 miu / ml were never observed when hcg was of placental origin . when hcg is less than 5.0 miu / ml , fsh testing is not performed as pregnancy is unlikely .\nwhen hcg is greater than 14.0 miu / ml , fsh testing is not performed as this is consistent with pregnancy ( gronowski et al . , 2008 ) .\nin one study , two weeks of estrogen - progesterone therapy suppressed pituitary hcg and may help confirm diagnosis ( cole et al . , 2007 ) .\ngestational trophoblastic disease is a group of conditions that may be classified as either premalignant , in the case of a partial or complete hydatidiform mole , or malignant , including invasive mole , choriocarcinoma , placental - site trophoblastic tumor and epithelioid trophoblastic tumor .\nalthough not always the case , -hcg is commonly found to be elevated in these conditions and these diseases are considered high on the differential diagnosis list when found .\nphantom hcg is a phenomenon first described in 1998 by laurence cole , ph.d . , where patients have persistent mild elevations of -hcg , occasionally following miscarriage .\nthe elevated -hcg often falsely interpreted and misleads physicians to evaluate or incorrectly treat patients with cytotoxic agents for trophoblast disease ( cole , 1998 ) .\nheterophilic antibodies against mouse , goat , rabbit , cow , horse , or sheep antigens can interfere with two - site immunoassays by creating complexes between the two anti--hcg antibodies without -hcg being present .\nthis leads to a false - positive result ( vladutiu et al . , 1982 ) .\npeople can develop heterophilic antibodies by exposure to the serum , tissue , or other antigens of nonhuman species .\nheterophilic antibodies do not appear to be excreted in the urine and therefore urine assays can be used to identify false - positive serum results .\nserial dilutions may also be performed to assess for interference . to avoid false positives ,\nthe excess of nonspecific antibodies saturates heterophilic antibodies in human serum and usually eliminates their interference with the assay ( johnson et al . , 2000 ) .\nadditionally , serum samples can be sent to outside laboratories with different assay systems to validate results . in our patient 's case ,\nthe patient continued to have normal menstrual cycles and was using two forms of contraception with her husband who had history of vasectomy .\nthe work up , including pelvic ultrasound and ct scans , was negative for pregnancy and trophoblastic disease .\nit was therefore believed that the patient 's -hcg production was due to the patient 's tumor , consistent with a paraneoplastic syndrome .\nparaneoplastic syndromes occur in about 8% of cancer patients and frequently develop with advanced disease .\nthey may appear earlier than symptoms of the primary tumor itself , leading to new diagnosis of cancer ( pelosof and gerber , 2010 ) .\nit can also be found in the testis , liver , lung , colon , and stomach in small amounts .\nmalignancies in these organs may lead to an increased serum levels ( demirtas et al .\na gastric origin is the most frequent , ranging from 11% to 17% of this rare subset ( germann et al . , 2002 ) .\nin our case , the patient had a primary ovarian neoplasm with metastases within the abdomen .\n-hcg levels rose while the patient was on a treatment break , nearly impeding her from further treatment . with re - initiation of therapy\n, the -hcg declined , corresponding to a partial response per response evaluation criteria in solid tumors ( recist ) on radiographic imaging .\nurine hcg remained positive despite decline in serum hcg as the level was still over the detection threshold of 25 \ninteresting enough , other tumor markers ( ca 125 , ca 15 - 3 , ca 19.9 and cea ) all increased .\nthe decreased size of tumor within the pelvis corresponded with decreasing -hcg levels while increased hepatic metastasis corresponded to increases in other markers .\nthis lends evidence to the idea that the patient had tumoral heterogeneity with different markers produced by tumors in different areas of the body .\nthis is the first case of paraneoplastic -hcg production from an ovarian adenocarcinoma reported in the literature .\nwe provide a treatment algorithm to evaluate for paraneoplastic hcg production when assessing for clinical trial eligibility ( fig .\nparaneoplastic syndrome should remain in the differential diagnosis in patients found to have elevated levels of -hcg without evidence of intra- or extra - uterine pregnancy .\ninformed consent to publish the information was granted from the patient . none of the authors have conflict of interest or competing interest .\njg participated in the design of the manuscript , analyzed the biomarker data and drafted the manuscript .\npp jg participated in the design of the manuscript , analyzed the biomarker data and drafted the manuscript .\nsp conceived of the study , and participated in its design and coordination and helped to draft the manuscript .", "answer": "there is a broad range of possible diagnoses for an elevated beta human chorionic gonadotropin ( -hcg ) in the absence of intrauterine or ectopic pregnancy . when women of child bearing potential undergo evaluation for clinical trial , it is often unclear what course of evaluation to take when a pregnancy test is positive . \n we describe the clinical course of a patient with widely metastatic mucinous ovarian carcinoma with metastasis to the peritoneum , lymph nodes and liver . the patient was found to have a mildly elevated -hcg during initial evaluation for clinical trial . \n extensive work up for ectopic pregnancy , trophoblastic disease , and phantom -hcg were negative . \n the patient 's -hcg levels continued to rise until initiation of therapy . \n she was treated on a phase i protocol with restaging scans revealing a partial response . \n the -hcg was retested and declined in conjunction with her response , consistent with paraneoplastic -hcg . here \n , we propose a decision making algorithm to evaluate a patient with an elevated -hcg undergoing assessment for clinical trial .", "id": 187} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 45-year - old man presented to our outpatient department with painless progressive diminution of vision both eyes for the past 10 days .\nmedical history included xdr - tb on treatment with linezolid ( 600 mg / day ) , ethambutol ( 800 mg / day ) , moxifloxacin ( 400 mg / day ) , cycloserine ( 500 mg / day ) , ethionamide ( 500 mg / day ) , and kanamycin ( 750 mg / day ) for the past 6 months .\non examination , his visual acuity was 20/200 ( ou ) , not improving with pin hole .\nanterior segment examination was unremarkable and pupils were 3 mm , round , regular , and reacting to light in both eyes ( direct and indirect ) .\nfundus examination revealed hyperemic disc with blurred margins ( ou ) [ figs . 1 and 2 ] .\nvisual field evaluation by humphrey field analyzer showed peripheral constriction and quadrantanopia in the right eye [ fig . 3 ] and low reliable fields in the left eye [ fig . 4 ] .\noptical coherence tomography ( oct ) revealed increased retinal nerve fiber layer ( rnfl ) thickness in both eyes [ fig . 5 ] .\nfundus photograph showing disc edema in right eye fundus photograph showing disc edema in left eye visual field showing peripheral constriction and superotemporal quadrantanopia in right eye visual field left eye showing quadrantanopia ( low reliability ) stratus oct showing increase in retinal nerve fiber layer thickness involving superior and inferior quadrants in right eye and superior , inferior , and nasal quadrants in left eye ( arrows ) ethambutol - induced toxic optic neuropathy was initially suspected and tablet ethambutol was discontinued after discussing with the treating physician .\nafter two weeks , the patient 's visual acuity had dropped to 20/400 in both eyes , and the fundus picture remained unchanged .\nhence , the possibility of toxic optic neuropathy due to linezolid was considered as reported in the literature and linezolid was discontinued ( a total cumulative dose of 126 g had been already consumed by the patient ) .\ncolor vision was restored to normal and patient 's vision was restored to 20/20 after one month .\nfundus examination revealed resolved optic disc edema with setting in of temporal pallor in both eyes [ figs .\nthe patient is under regular follow - up and no toxic effects have been noted at three months of follow - up .\nfundus photograph showing resolved disc edema with temporal pallor of optic disc in right eye fundus photograph left eye showing temporal pallor of optic disc follow - up visual field after discontinuation of linezolid showing partial recovery in right eye follow - up visual field in left eye after discontinuation of linezolid stratus oct showing reduction in retinal nerve fiber layer edema in both eyes\ntoxic optic neuropathies are characterized by gradual , progressive , painless , bilaterally symmetric visual loss affecting central vision , and causing central or centrocecal scotoma .\nxdr - tb is defined as resistance to at least rifampicin and isoniazid among the first - line anti - tb drugs ( which is the definition of multidrug - resistant tb ) in addition to resistance to any fluoroquinolone and at least one of the three injectable second - line anti - tb drugs ( capreomycin , amikacin , kanamycin ) .\nlinezolid inhibits protein synthesis by preventing formation of the ribosome complex that initiates protein synthesis .\nits unique binding site located on 23s ribosomal rna of the 50s subunit results in no cross resistance with other drug classes .\nhence , linezolid is being increasingly used for the treatment of infections caused by multidrug - resistant gram - positive bacteria .\nlong - term linezolid interferes with bacterial ribosomes and also with mammalian ribosomes , thereby disrupting mitochondrial oxidative phosphorylation and protein synthesis .\nserious adverse reactions demanding withdrawal of the drug include myelosuppression , peripheral and optic neuropathy , lactic acidosis , and serotonin syndrome .\nthe safety of linezolid treatment has been established for use only up to 28 days .\nthere are several case reports of linezolid - induced optic or peripheral neuropathy in patients treated for a time period beyond 28 days .\nonly two cases of toxic optic neuropathy have been reported following short - term linezolid treatment of 16 days .\nfundus picture can be varied , showing temporal pallor , disc edema , or essentially normal .\nthe most common indication for long - term linezolid therapy in these patients has been infection with methicillin - resistant staphylococcus aureus . in our case\n, neuropathy occurred after linezolid had been used for six months at a dose of 600 mg per day for infection with mycobacterium tuberculosis .\nwe attribute toxic optic neuropathy to linezolid in our patient because even two weeks after stopping ethambutol there was deterioration of vision , and it was only after withdrawal of linezolid that visual improvement started .\nlinezolid is recommended by the world health organization ( who ) to treat drug - resistant tuberculosis as a medicine with unclear efficacy .\nlinezolid , approved for gram - positive infections in 2000 has been used off - label for drug - resistant tuberculosis .\nthere is limited data available regarding the efficacy and safety of linezolid in multidrug - resistant tb since it is always administered as part of combination therapy .\nlinezolid may improve the chance of bacteriological cure only in the most complicated xdr - tb cases .\nits safety profile precludes its use in cases for which there are other alternatives . with increasing emergence of xdr - tb , for which treatment options are limited , physicians are compelled to resort to new drug therapies .\nalthough ethambutol is the most common antitubercular drug implicated to cause toxic optic neuropathy , it is pertinent to be aware that if withdrawal of one drug does not show visual recovery or there is further deterioration of vision , the possibility of toxicity due to other drugs should be thought of . with our country bearing the brunt of tuberculosis ,\nophthalmologists and physicians must be aware that monitoring of visual function is important in patients on long - term linezolid therapy and that early recognition of toxicity and discontinuation of drug results in complete visual recovery .", "answer": "many systemic antimicrobials have been implicated to cause ocular adverse effects . \n this is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect . \n we describe a case of progressive loss of vision associated with linezolid therapy . a 45-year - old male patient who was on treatment with multiple second - line anti - tuberculous drugs including linezolid and ethambutol for extensively drug - resistant tuberculosis ( xdr - tb ) presented to us with painless progressive loss of vision in both eyes . \n color vision was defective and fundus examination revealed optic disc edema in both eyes . \n ethambutol - induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn . \n deterioration of vision occurred despite withdrawal of ethambutol . \n discontinuation of linezolid resulted in marked improvement of vision . \n our report emphasizes the need for monitoring of visual function in patients on long - term linezolid treatment .", "id": 188} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary hyperhidrosis is a common disease that is characterized by excessive sweating of face , palms , or axilla , occurring in 0.6 - 3% of a population ( 1 , 2 ) .\nsince kux performed endoscopic thoracic sympathetic surgery ( 3 ) , it has been popular during the past few decades as the surgical treatment of choice for facial , palmar , and axillary hyperhidrosis ( 4 - 6 ) .\nalthough endoscopic thoracic sympathetic surgery offers permanent cure for hyperhidrosis , it is often accompanied by serious complications , such as compensatory hyperhidrosis . in order to decrease compensatory hyperhidrosis , endoscopic thoracic\nsympathetic surgery has attempted to reduce the extent of resection of the sympathetic nerve , but these procedures did not significantly decrease the occurrence of compensatory hyperhidrosis ( 7 ) .\nwe performed sympathetic nerve reconstruction surgery using intercostal nerve in 19 patients with severe compensatory hyperhidrosis after endoscopic thoracic sympathetic surgery and evaluated the results of the procedure .\nfrom february 2004 to august 2007 , we performed endoscopic thoracic sympathetic surgery in 184 patients with primary hyperhidrosis . among theses\npatients , reconstruction surgery of sympathetic nerve using intercostal nerve was performed in 19 patients with severe compensatory hyperhidrosis after endoscopic thoracic sympathetic surgery .\nfourteen patients were male and 5 were female ( median age : 28 yr , range : 19 - 61 ) .\nthis study was approved by the institutional review board of our hospital ( irb no : 3 - 20080021 ) .\nall procedures of reconstruction surgery were performed under general anesthesia with a single lumen endotracheal tube .\nthe patients were in a semi - fowler position with their arms extended . in 18 patients except for one patient with severe pleural adhesion ,\nstarting on the left side , two separate skin incisions were made along the previous thoracoscopic scars and thoracoscopic ports were placed .\nafter co2 gas insufflation into the thoracic cavity with less than 10 mmhg of pressure to deflate the lung , the pleural space was inspected with 5-mm thoracoscope .\nthe intercostal neurovascular bundle was dissected in lengths of 5 - 7 cm and the distal part was resected .\nafter the proximal and distal part of previously operated sympathetic nerve was exposed , the nerve sheaths of proximal and distal part of exposed sympathetic nerve and harvested intercostal nerve end were removed with an electro - surgical tip cleaner ( surgisite , ethicon , gargrave , skipton , uk ) .\nthe intercostal nerve end was placed between the proximal and distal part of the exposed sympathetic nerve and the fibrin glue was applied to contact surface of the sympathetic and intercostal nerve ( fig .\nthe same procedure was repeated on the right side . in cases of sympathetic nerve clipping\n, this procedure was performed after clip removal . in one patient with severe pleural adhesion\nwe reviewed the clinical charts of all patients who underwent sympathetic nerve reconstruction surgery using the intercostal nerve .\npatients were followed by telephone questionnaire on the effects of the surgery and postoperative complications .\nthe degree of improvement of compensatory hyperhidrosis was graded as \" definite \" , \" mild \" , or \" absent \" .\n\" definite \" means that patients felt fully satisfied after the reconstruction surgery , \" mild \" means that patients felt satisfied to a certain extent , and \" absent \" means that patients felt no improvement .\nmedian interval between the sympathetic nerve reconstruction surgery and questionnaire was 22 ( range : 1 - 45 ) months .\nin one patient ( patient number 17 in table 1 ) , digital infrared thermographic imaging was performed preoperatively and postoperatively .\nprimary hyperhidrosis patients were composed of 9 facial , 8 palmar , and 1 axillary , and one patient had both facial and palmar hyperhidrosis .\ninitial endoscopic thoracic sympathetic surgery for primary hyperhidrosis was t3 sympathicotomy in 5 patients ; t2 sympathicotomy in 8 ; t2 , 3 sympathicotomy in 1 ; t2 , 3 , 4 sympathicotomy in 1 ; t2 clipping in 2 ; t2 , 3 clipping in 1 ; and t2 clipping with t3 sympathicotomy in 1 patient .\nthe median interval between the first endoscopic thoracic sympathetic surgery for primary hyperhidrosis and sympathetic nerve reconstruction surgery was 47 ( range , 4 - 111 ) months .\nr3 intercostal nerve was used for sympathetic nerve reconstruction surgery in 15 patients , r4 intercostal nerve in 2 , r2 intercostal nerve in 1 , and r3 with r5 intercostal nerve in 1 patient .\nthree patients replied that the effects of reconstruction were \" definite \" , 6 responded with \" mild \" , and 8 said \" absent \" .\npostoperative complications were numbness of the chest wall in 2 patients , chest wall pain in 2 patients , and temporary ptosis in 1 patient in whom ptosis spontaneously resolved after 3 months .\npreoperative and postoperative digital infrared thermographic imagings performed in one patient showed the thermal change in chest and back .\nsince kux advocated thoracoscopic sympathetic surgery ( 3 ) , recent developments in thoracoscopy and specialized instruments have facilitated the procedure . and , it became the treatment of choice for hyperhidrosis because of its low morbidity , short hospital stay , and excellent cosmetic results ( 6 ) .\nalthough it has many advantages , some patients suffer from compensatory hyperhidrosis , which is by far the most common and disagreeable complication after endoscopic thoracic sympathetic surgery . according to the previous reports\n, compensatory hyperhidrosis occurs in 59.8 - 90% of patients after sympathetic surgery ( 8 - 10 ) .\nthe mechanism of compensatory hyperhidrosis is not clear , but it seems to be associated with compensation for thermoregulatory function ( 11 , 12 ) . because the incidence and degree of compensatory hyperhidrosis appear to be related to the extent of resection of the sympathetic chain , some clinicians have suggested that the extent of resection should be limited ( 13 ) . for these reasons , many treatment methods , such as different level sympathectomy or sympathicotomy , ramicotomy , and clipping ,\nhave been attempted to reduce the extent of resection ( 14 - 18 ) , although the effects of these methods remain controversial . in mild compensatory symptoms , antiperspirants including aluminum - based compounds , iontophoresis , and systemic or topical anticholinergic drugs can be used . however ,\nif the symptoms are severe , the management is more difficult and results are unsatisfactory .\nsince philipeaux and vulpian reported the first experimental nerve graft in 1870 , many successful nerve grafts were reported in the field of orthopedic surgery . in the field of thoracic surgery ,\nschoeller et al . ( 19 ) reported successful phrenic nerve reconstruction using sural nerve in patient with mediastinal tumor resection .\ntelaranta reported that reconstruction of the sympathetic chain using sural nerve graft diminished compensatory sweating in a male patient who underwent sympathicotomy for palmar hyperhidrosis ( 20 ) .\nmiura et al . ( 21 ) reported that sympathetic nerve reconstruction surgery using the intercostal nerve was useful after resection of the sympathetic nerve involved by tumor .\nalthough the sural nerve is the most commonly used for nerve graft , the intercostal nerve has several advantages over the sural nerve .\nfirst , the intercostal nerve has more sympathetic nerve fibers than the sural nerve , hence the intercostal nerve is more appropriate for sympathetic nerve reconstruction surgery .\nsecond , the sural nerve can be used only as free graft but the intercostal nerve can be used as pedicled graft and harvested as a neurovascular bundle . therefore , a sufficient blood supply in the graft can be maintained .\nso , an additional incision is not needed and donor site morbidity decreases . in our experience ,\nthoracoscopic intercostal nerve could be harvested in all patients except 1 patient with severe pleural adhesion , leading us to believe that the intercostal nerve is a useful graft for sympathetic nerve reconstruction surgery .\nepineural and fascicular sutures are the most used for nerve anastomosis , but the foreign body reaction caused by suture material to nerve is another possible problem ( 22 , 23 ) .\nsome reports demonstrated the successful nerve anastomosis using fibrin sealant without suture technique ( 24 , 25 ) .\nif microscopic suture technique is used in sympathetic nerve reconstruction surgery , it inevitably needs thoracotomy .\nthe type of anastomosis performed in this procedure is the modification of end - to - side neurorrhaphy where axonal sprouting occurs ( 26 ) . the nerve is generally anastomosed in the original direction , but the free graft should be prepared to be anastomosed in the original direction in this operation .\nsome reports revealed the anastomosis in reverse orientation did not influence the nerve conduction ( 27 , 28 ) . in the questionnaire on the effects of sympathetic nerve reconstruction surgery , nine patients replied \" definite \" or \" mild \" . in 3 patients who replied that the results were \" definite \" ,\ncompensatory sweating decreased and anhidrosis of the affected areas after endoscopic thoracic sympathetic surgery improved .\npatients , who replied mild improvement , complained still uncomfortable compensatory hyperhidrosis , although amount and frequency of perspiration decreased .\nthese results of the reconstruction surgery were not different between variables such as age , sex , affected area , and interval from endoscopic thoracic sympathetic surgery due to the small number of cases in this study .\nthe digital infrared thermographic imaging is a useful tool in evaluation of body temperature distribution . in the image ,\nbefore and after sympathetic nerve reconstruction , we performed the digital infrared thermographic imagings in 22 yr - old man complaining of compensatory hyperhidrosis in chest after t3 sympathicotomy .\nafter the reconstruction surgery , trunk temperature has increased , and this result corresponded with patient 's symptom . even though the number of patients is not sufficient for data analysis , outcome of the reconstruction surgery did not correlate with the interval between the sympathetic surgery and reconstructive surgery . to evaluate the exact effects of sympathetic nerve reconstruction , more cases and longer\npostoperative complications of the reconstruction surgery were seen in 5 patients ; prolonged chest wall pain which was tolerable in 2 patients , and numbness of chest wall in 2 patients .\nin addition , because compensatory hyperhidrosis depends on climate and season , the timing of a questionnaire survey is important . in this study , the questionnaire was performed on october when it is relatively cool and dry in korea .\n, our results suggest that sympathetic nerve reconstruction with intercostal nerve may be one of the useful surgical methods in severe compensatory hyperhidrosis patients .\nthe reconstruction surgery must be decided very carefully in highly selected patients with severe compensatory hyperhidrosis .", "answer": "we performed sympathetic nerve reconstruction using intercostal nerve in patients with severe compensatory hyperhidrosis after sympathetic surgery for primary hyperhidrosis , and analyzed the surgical results . from february 2004 to august 2007 , sympathetic nerve reconstruction using intercostal nerve was performed in 19 patients . \n the subjected patients presented severe compensatory hyperhidrosis after thoracoscopic sympathetic surgery for primary hyperhidrosis . \n reconstruction of sympathetic nerve was performed by thoracoscopic surgery except in 1 patient with severe pleural adhesion . \n the median interval between the initial sympathetic surgery and sympathetic nerve reconstruction was 47.2 ( range : 3.5 - 110.7 ) months . \n compensatory sweating after the reconstruction surgery improved in 9 patients , and 3 out of them had markedly improved symptoms . \n sympathetic nerve reconstruction using intercostal nerve may be one of the useful surgical options for severe compensatory hyperhidrosis following sympathetic surgery for primary hyperhidrosis .", "id": 189} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhemophilia a is a congenital disease transmitted by the x chromosome with a recessive trait , characterized by a deficiency in the production of factor viii .\nthe hemophilic pseudotumor affects 12% of patients with a severe disease , frequently associated with a traumatic injury .\nthe hemophilic pseudotumor develops from repeated episodes of bleeding , either from fracture sites or bleeding or subperiosteal hemorrhage of any soft tissue .\nthe interior of the pseudotumor consists of blood products at different stages of development , surrounded by a fibrous capsule containing hemosiderin - laden macrophages .\nit appears as a painless tumor of slow growth that can compress key organs causing bone destruction , muscle and skin necrosis .\nthe objective of case presentation is to describe a patient with a hemophilic pseudotumor of the abdomen , and to review the literature on hemophilic pseudotumor .\nthis is a case of a 31 year old male , diagnosed with severe hemophilia a at 2 years of age , treated with factor vii 2000 iu weekly since , whit a family history of 2 cousins with hemophilia ( no other specified ) . in september 2011 , he underwent drainage of a hematoma of the left pelvic limb . in october 2011\nblood transfusion on multiple occasions . in august 2012 had a hematoma in the left thigh surgically removed . in september 2012 presented upper gastrointestinal bleeding requiring hospitalization with remission of the symptoms .\nan abdominal tumor diagnosed 10 years ago during routine screening that progressively grew to encompass the entire abdominal area , with no associated symptoms . during his last hospital admission , hematology referred him to general surgery due to bowel obstruction symptoms , and to evaluate surgical treatment of a pelvic tumor referred as a possible teratoma . a ct scan of the abdomen ( figs . 1 and 2 )\nwas performed , showing a tumor in the pelvis with clear borders , 241 mm 192 mm of diameter , from the pelvis and projected into the bladder , rectum and adjacent structures , including the kidneys .\nthe lesion had irregular wall thickness , with a density of 195 houndsfield units in its interior , with heterogeneous enhancement and vascularity present within ; with tomographic diagnosis of abdominal pelvic teratoma .\nthe patient underwent surgery with surgical findings that included a cyst - like tumor of 40 cm 30 cm displacing loops of small bowel , colon and bladder , with adhesions to the great omentum , small intestine , descending colon and bladder .\nmacroscopically appeared as an old , organized , and calcified clots with a volume of 5000 ml .\nan abdominal tumor diagnosed 10 years ago during routine screening that progressively grew to encompass the entire abdominal area , with no associated symptoms . during his last hospital admission , hematology referred him to general surgery due to bowel obstruction symptoms , and to evaluate surgical treatment of a pelvic tumor referred as a possible teratoma . a ct scan of the abdomen ( figs . 1 and 2 )\nwas performed , showing a tumor in the pelvis with clear borders , 241 mm 192 mm of diameter , from the pelvis and projected into the bladder , rectum and adjacent structures , including the kidneys .\nthe lesion had irregular wall thickness , with a density of 195 houndsfield units in its interior , with heterogeneous enhancement and vascularity present within ; with tomographic diagnosis of abdominal pelvic teratoma .\nthe patient underwent surgery with surgical findings that included a cyst - like tumor of 40 cm 30 cm displacing loops of small bowel , colon and bladder , with adhesions to the great omentum , small intestine , descending colon and bladder .\nmacroscopically appeared as an old , organized , and calcified clots with a volume of 5000 ml .\nthe hemophilic pseudotumor of the abdomen is a rare but often disabling condition , potentially fatal in patients with severe hemophilia . diagnosing a hemophilic pseudotumor with invasive techniques such as , aspiration and biopsy\nimaging techniques of which mri is preferred , allows recognition of blood products in various stages of evolution .\nultrasonography ( usg ) shows a central anechoic region with increased echoes behind the lesion due to enclosed fluid in the pseudotumor . computed tomography ( ct )\nidentifies the thick pseudocapsule , but can not differentiate a hematoma from a chronic abscess .\nct is particularly helpful in the evaluation of bone , whereas mri is superior to ct for delineating soft tissue . at the moment ,\nhowever , there are instances where surgical extraction of the lesion is not feasible . in such situations ,\nthe decision to operate on this patient was made based on the gradual increase in the tumor size , the symptoms that the displayed by the patient . in this patient\nthis type of procedure is associated with complications such as bleeding , bowel perforation , and damage to nearby structures due to firm vascular , and nervous adhesions . surgical resection after performing arterial embolization to reduce the vascularization of the pseudotumor is a good alternative , thereby reducing the size of the pseudotumor and the risk of bleeding complications during surgery , at best about 2 weeks prior to surgery .\nit is a rare pathological entity , but it must be considered in the hemophilic patient with a long - standing abdominal tumor and trauma history , to plan appropriate treatment .\nthe abdominal hemophilic pseudotumor is a rare pathological entity , with few reports worldwide , but must be considered in hemophilic patients with a well documented abdominal tumor , as a complication of the hematologic disease .\nsigns and symptoms of compression should be evaluated by ct or mri because its early diagnosis is crucial for evaluation and proper surgical planning , and treatment in conjunction with other specialties .\nwritten informed consent was obtained from the patient for publication of this case report and case series and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .\nthe study conception and design , as well as writing the manuscript works were all equally distributed among all the authors.key learning pointshemophilic pseudotumor etiology.hemophilic pseudotumor management .", "answer": "introductionhemophilic pseudotumor is a rare complication that occurs in patients with severe hemophilia . \n results from multiple episodes of bleeding into the bones and soft tissues.presentation of casea 31 years old male patient , with severe hemophilia a. diagnosed with an abdominal tumor 10 years ago during routine screening , that progressively grew to encompass the entire abdominal area , with symptoms of intestinal obstruction.discussionhemophilic pseudotumor appears as a painless tumor of slow growth that can compress vital organs producing bone destruction , muscle and skin necrosis . \n the tumor may have fistulas or break spontaneously.conclusionthe abdominal hemophilic pseudotumor is a rare pathological entity , with few reports worldwide , but must be considered in hemophilic patients with a well documented abdominal tumor .", "id": 190} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nskin wounds are caused by the loss of connection in the skin and recovery requires cellular and biochemical reactions .\nchronic wounds arise from the lack of physiological processes and the disease due to complications ( e.g. infection and amputation ) has devastating consequences on societies . according to the principles of iranian traditional medicine ( itm )\nthis is a systematic review study that involved gathering data from three traditional medical textbooks , namely canon of medicine , tib - e - akbari and exir - e - azam with the keyword chronic wound or\nfew tables were developed for nutrition measures as well as edible and topical medicinal herbs .\nelectronic databases such as pubmed , scopus , web of science , and cochrane library were searched for relevant articles and those related to effective medicinal herbs in the treatment of wounds were obtained .\ndepending on appearance and secretions , wounds are divided into two categories , namely simple and compound wounds .\nthe prognostic factors are based on the age , weight , accompanied disease , as well as the quality and quantity of the wound secretions .\npatient s diet is very important and oral medications have a major role in the whole body detoxification .\ntopical medications are used together with the above - mentioned treatments ; noting that without detoxification , these medications are not effective entirely .\nbody detoxification is the first medical step , after which topical medications could lead to a better wound healing result .", "answer": "background : skin is the body s first defense against stressful factors . \n skin wounds are caused by the loss of connection in the skin and recovery requires cellular and biochemical reactions . \n chronic wounds arise from the lack of physiological processes and the disease due to complications ( e.g. infection and amputation ) has devastating consequences on societies . according to the principles of iranian traditional medicine ( itm ) \n , these disorders can be treated in a step - by - step procedure.methods:this is a systematic review study that involved gathering data from three traditional medical textbooks , namely canon of medicine , tib - e - akbari and exir - e - azam with the keyword chronic wound or ghorha . in the next step , \n few tables were developed for nutrition measures as well as edible and topical medicinal herbs . \n electronic databases such as pubmed , scopus , web of science , and cochrane library were searched for relevant articles and those related to effective medicinal herbs in the treatment of wounds were obtained.results:depending on appearance and secretions , wounds are divided into two categories , namely simple and compound wounds . \n the prognostic factors are based on the age , weight , accompanied disease , as well as the quality and quantity of the wound secretions . \n wound treatments include medical nutrition therapy , edible medications , and manipulation therapies . \n patient s diet is very important and oral medications have a major role in the whole body detoxification . \n topical medications are used together with the above - mentioned treatments ; noting that without detoxification , these medications are not effective entirely.conclusion:wound healing requires physiological processes within the body . from the perspective of itm , \n body detoxification is the first medical step , after which topical medications could lead to a better wound healing result .", "id": 191} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nclear - cell sarcoma ( ccs ) is a rare malignant connective tissue tumor that was first described by enzinger in 1965 .\nccs occurs most commonly in adolescents and young adults and the patients aged > 60 years are rare .\nit has a high rate of local recurrence , regional lymph node metastasis , and distant metastasis [ 1 , 2 ] .\nccs occurs most commonly in the deep soft tissues of the extremities , with rare involvement of the head , neck , and trunk .\nwe experienced a very rare case of primary ccs in the mediastinum with successful surgical resection in an elderly patient .\nin october 2011 , a 63-year - old man presented with a mass in the right upper mediastinum on chest radiograph .\ncomputed tomography showed a large oval mass ( 55 55 85 mm ) with clear margins and heterogeneous enhancement in the right upper posterior mediastinum between the phrenic nerve and vertebrae ( fig .\n1b ) , and 18f - fluorodeoxyglucose positron emission tomography showed abnormal uptake with a maximum standardized uptake value of 15.1 .\nthe tumor was excised by video - assisted thoracoscopic surgery , with negative surgical margins .\nthe tumor was soft , well circumscribed , encapsulated , and did not invade the pleura .\nhistological examination of the resected tumor with hematoxylin and eosin ( he ) staining showed morphological features compatible with conventional soft tissue ccs .\nthe tumor cells were distributed in nests separated by fibrous connective tissue , showing an alveolar pattern ( fig .\nthe tumor cells had eosinophilic and clear cytoplasm and oval vesicular nuclei of varying sizes with characteristic prominent eosinophilic nucleoli .\n2c ) , s-100 protein , calretinin , cd34 , cd56 , cd68 , and cd117 ; and negative for melan - a , cytokeratins ae1ae3 , cytokeratin cam5.2 , chromogranin a , desmin , caldesmon , myogenin , epithelial membrane antigens , cd57 , cd99 , and d2 - 40 .\nccs is a very rare soft tissue neoplasm , which occurs in the extremities in 9095% of cases .\nour case was diagnosed with a primary ccs in the mediastinum . a search of the english literature revealed only one previously reported case of primary ccs in the mediastinum .\nrecent cytogenetic studies showed that ccs is associated with the translocation t(12;22 ) ( q13;q12 ) ; this translocation is observed in up to 93% of patients with ccs , but never observed in malignant melanoma . in our case\n, we were unable to determine whether this translocation was present , because of the lack of availability of such analysis in japan .\nthe rarity of ccs in the mediastinum makes it difficult to draw conclusions regarding prognostic factors .\nreported that complete excision of the primary tumor with wide surgical margins appears to be the optimal approach to treatment , with or without adjuvant radiation therapy .\nccs is an aggressive malignant tumor , and unlike most soft tissue sarcomas , it often metastasizes to regional lymph nodes . in our case\n, we did not have a definitive diagnosis at the time of operation , and therefore we did not perform excision of the tumor with wide margins or dissect the regional lymph nodes . in most cases , ccs has a relentlessly progressive course and results in death because of widespread dissemination .\nthe reported overall survival rates without local recurrence are 30% at 5 years and 16% at 10 years .\nsome patients experience rapidly fatal progression , and late metastasis after many years of freedom from disease is also relatively common .\nwe believe that regular long - term follow - up with computed tomography , magnetic resonance imaging , and 18f - fluorodeoxyglucose positron emission tomography examination is important to identify local recurrence or distant metastasis as early as possible .", "answer": "we report a case of primary clear - cell sarcoma ( ccs ) in the mediastinum . in october 2011 \n , a 63-year - old man was admitted to our hospital for surgical resection . \n the tumor was completely excised by video - assisted thoracoscopic surgery . \n the tumor was well encapsulated and did not invade the pleura . \n histological examination led to a final diagnosis of primary ccs in the mediastinum . \n the patient remains alive without evidence of recurrence at 15 months after surgery .", "id": 192} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese conditions may be life - threatening ( e.g. oral cancers ) or not , progressing ( caries , periodontitis , etc . ) or not , dealing with aesthetics ( staining in anterior teeth such as molar \nincisor hypomineralisation ( mih ) ) or pain ( pulpitis , mih in posterior teeth , etc . ) .\nohrqol is highly subjective and has to be assessed within the framework of patients conditions , sociocultural environments and own experiences and states of mind : because ohrqol is related to daily life and is unique to each individual , even patients with severe conditions can report having good quality of life .\nfurthermore , quality of life is by itself multi - faceted , showing variation over time for each individual .\nohrqol should therefore be assessed longitudinally to take into account changes over time , using versatile tools .\nthis means having relevant questions with well - defined items and being able to analyse answers in a good way .\nmany limitations can be found to the current validation testing , including relevance of the questions , validity and sensitivity to change , risk of misinterpretations ( role of the ethnocultural environment ) , problems of translation of english questionnaires and difficulty to interpret the significance of a psychometric measurement when reported simply as a numerical score or a mean [ 1 , 2 ] .\nthis latter point is of importance since the same score can be obtained from people answering in a different way to a majority of questions . finally , patient - based outcome measures ( as named by fitzpatrick et al . )\nshould provide the opportunity to measure the extent or intensity of the changes in ohrqol .\nvarious psychometric instruments have also been used to measure ohrqol ( tables 1 and 2 ) [ 1 , 4 ] .\nthese are based on different criteria that enable them to be more or less patient- or expert - centred .\nsome are generic ( ohip1 - 49 , ohip-14 , oidp , oh - qol , sf-362 ) and can be considered as core indicators ; others are adapted to specific conditions / domains ( orthognathic qol questionnaire , sooq for orthodontic surgery , ohip - aesthetic,3 ohrqol for dental hygiene ) or populations ( cohqol and child - oidp for children , gohai for elderly people , etc.).table 1conceptual and structural basis of psychometric instruments used in dentistry ( adapted from brondani and mcentee ) instrumentsacronymstructural originsempirically basedconnotation of questionsnumber of questionssocial impacts of dental diseasesiddsipyesn14oral health impact profileohipicidhyesn49geriatric ( generic ) oral health assessment indexgohaiicidh and sipyesn and p12oral health - related qol instrumentohrqlmultiplenon36oral impact on daily performancesoidpicidhnon8dental impact on daily livingdidlsipyesn and nt and p36dental impact profiledipsipyesn and nt and p25oral health - related quality of life measureohqolmultiplenon3oral health quality of life inventoryoh - qolsipunclearp15rand dental questionnaireunspecifiedsipnon3oral health questionnaireunspecifiedicidhunclearn and nt and p70oral health quality of life ukohqol - ukicidh2yesn and p16subjective oral health status indicatorssohsimultiplenon and nt34liverpool oral rehabilitation questionnairelorqunclearnon40self - rated oral healthsrohicidhnon and p3dentaldentalunclearnon15dental health status quality of life questionnaireds - qolgeneric qol instrumentnon and punclearn 1/4 negative , nt neutral , p positive , sip sickness impact profile , icidh international classification of impairments , disabilities and handicapsinformation derived from open - ended interviewssome indicators present shorter or extended forms other than the original versionhealth - related models : natural history of disease model and sipdeveloped from existing measures ( rand , oral facial pain index , etc.).table 2oral health outcome measures developed before 2007 ( adapted from locker and allen ) pre-1997 ( presented at the 1997 conference ) social impacts of dental diseasegeneral ( geriatric ) oral health assessment index ( gohai)dental impact profile ( dip)oral health impact profile ( ohip)oral impacts on daily performances ( oidp)subjective oral health status indicators ( sohsi)oral health - related quality of life measuredental impact on daily living ( didls)oral health quality of life inventoryrand dental questionspost-1997ohqol - ukchild oral health quality of life questionnaire ( cohqol)child oidpohrqol for dental hygieneorthognathic qol questionnairesurgical orthodontic outcome questionnaire ( sooq ) conceptual and structural basis of psychometric instruments used in dentistry ( adapted from brondani and mcentee ) n 1/4 negative , nt neutral , p positive , sip sickness impact profile , icidh international classification of impairments , disabilities and handicaps information derived from open - ended interviews some indicators present shorter or extended forms other than the original version health - related models : natural history of disease model and sip developed from existing measures ( rand , oral facial pain index , etc . ) .\noral health outcome measures developed before 2007 ( adapted from locker and allen ) the ohip , also called ohip-49 , is the most widely used , and this has enabled investigators to modify forms that can be subsequently adapted to populations or conditions .\nthe initial 49-question form was constructed to assess the social impact of oral disorders .\neach of the set of 49 statements represented one of seven domains : it is mainly expert - centred and constructed to select items according to their fit with a conceptual framework rather than on the basis of their importance to the patients from whom they were derived .\na shorter version of ohip restricted to 14 items ( ohip-14 ) was later proposed .\none major question is to know if we need to use either a generic questionnaire , an adapted form of a generic questionnaire or to construct a new questionnaire specific to the population or condition to be studied .\nconstructing or using one of these specific questionnaires may lead to many questions , for example , ( 1 ) is it made specifically for the purpose of research or for clinical practice ? or ( 2 ) how to adapt each questionnaire to local languages and cultures ?\nthis may subsequently lead us to consider the impact of dentin hypersensitivity ( dhs ) or exposed cervical dentin ( ecd ) on ohrqol of those individuals being assessed .\nvery few studies have been devoted to this aspect of dhs / ecd as recently shown , with only two papers written in english specifically dedicated to the evaluation of ohqol in dhs / ecd patients .\none paper provided results using a generic questionnaire and the second paper constructed a specific questionnaire to evaluate ohqol in dhs / ecd patients but provided no epidemiological results . these studies are more extensively described in an accompanying paper . in the future ,\nstudies using validated questionnaires specifically constructed to evaluate the impact of the condition on ohqol should be employed .\nthese questionnaires should be patient - centred and derived from interviews with patients who are expected to complete the questionnaire [ 4 , 10 ] . furthermore , if these studies also attempt to evaluate the efficacy of desensitising agents in reducing dhs / ecd and its subsequent impact on ohqol , then it is imperative that the condition should be clearly diagnosed by trained and calibrated dentists experienced in conducting clinical studies using recognised and accepted clinical criteria for the evaluation of dhs / ecd . due to the cultural and language differences between countries ,\nthere is also a need of norm or reference value(s ) for each population to be studied .\nfor example , when constructing a questionnaire for a non - english - speaking population , the questionnaire should be initially written in english , then translated by two people of the designated native ( foreign ) language and subsequently translated back into english by two native english - speaking people to identify any potential issues that may have arisen from the translation . finally , as indicated above , any future study attempting to evaluate the efficacy of a desensitising agent in reducing dhs / ecd and its subsequent impact on ohqol\nshould be conducted by experienced and calibrated examiners using established guidelines for conducting dhs / ecd clinical studies .\nsuch studies should also be based on a randomised clinical study design and include both placebo or control groups .\npatients suffering from dhs / ecd have been reported to have a significantly impaired ohrqol ; this may however be improved following treatment with a desensitising agent as reported by several authors .\nit is therefore of the upmost importance that the use of the ohrqol as a quality control tool in the dental office be established in robust clinical studies .\nfurthermore , because of its ability to reflect a patient s satisfaction with any proposed treatment , it may prove to be a valuable asset for practitioners when assessing their patients quality of life before , during and after treatment of various clinical conditions such as dhs / ecd .", "answer": "objectivesoral health - related quality of life ( ohrqol ) can be considered as the scientific expression of that part of a person s well - being that is affected by his / her oral health . \n the aim of this paper was to evaluate how to use the data available in the field of research to make a link between ohrqol and dentin hypersensitivity ( dhs ) in the dental office.materials and methodsresearch papers in the field of ohrqol and dhs and reviews and research papers about ohrqol were used for analysis in this short review , with a particular insight on the instruments used to evaluate ohrqol.resultsvarious psychometric instruments have been used to measure ohrqol that are more or less patient- or expert - centred . \n some are generic , others are adapted to specific conditions / domains or populations . \n the impact of dhs or exposed cervical dentin ( ecd ) on ohrqol has been assessed in very few studies . \n it is therefore of the upmost importance that the use of the ohrqol as a quality control tool be established in robust clinical studies.conclusions/clinical relevancefuture studies evaluating the impact of the dhs / ecd on ohqol or evaluating the efficacy of desensitising agents should respect some key points , including study design ( randomization , placebo / control group , etc . ) , validated specific questionnaires and trained calibrated practitioners .", "id": 193} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nstreptococcus pneumoniae remains a major cause of childhood morbidity and mortality worldwide , particularlyin lower income countries .\npneumococcal diseases are the leading source of vaccine preventable deaths , mostly due to community - acquired pneumonia ( cap ) , accounting for approximately 11% of all deaths in children under 5 years old ( 1 ) .\ncolonization of the nasopharynx is a necessary step along the path to pneumococcal disease ( pd ) ( 2 ) .\npneumococcal conjugate vaccines ( pcv ) reduce nasopharyngeal carriage of serotypes which included in the vaccine by conferring capsular - specific immunity .\nexperience from countries where conjugate vaccines have been introduced has shown rapid and sustained carriage reduction of vaccine serotypes ( vt ) following vaccination ( 3 ) .\nthe microorganism produces a plethora of virulence factors , including the polysaccharide capsule , several surface - located proteins , and the toxin pneumolysin ( 5 , 6 ) .\nthe polysaccharide capsule is highly efficient in protecting the bacteria from opsonophagocytosis ( 7 ) .\nsurface proteins of s. pneumoniae ( pneumococcus ) have been investigated for their role in pneumococcal pathogenicity and as candidate antigens for protein based vaccines ( 8) . among the surface - associated proteins ,\nthe pneumococcal surface protein a ( pspa ) andc ( pspc ) are the best characterised choline - binding proteins ( 6 , 9 ) .\npneumolysin is a cytoplasmic toxin released by autolysis of the cell and it is a very important virulence factor with multiple effects .\nthe major autolytic enzyme of the pneumococcus is lyta ( nacetylmuramoyl - l - alanine - amidase ) , which is responsible for the deoxycholate- and penicillin induced cell lysis in the stationary phase , having a great clinical importance ( 10 ) . the lyta - encoded major autolysin of s. pneumoniae is a member of a widely distributed group of cell wall - degrading enzymes located in the cell envelope and postulated to play roles in avariety of physiological functions ( 11 ) .\nrrga is a virulence factor in a murine lung infection model and has a varied distribution among serotypes of s.pneumoniae ( 12 ) .\ns. pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits , rrga , rrgb and rrgc ( 13 ) .\nsome of the pneumococcal virulence factors are potential targets for protein- based pneumococcal vaccine production .\nthus , in this study the presence of three genes were detected among the isolates of s. pneumoniae .\na total of 260 samples from nasopharynx of healthy children under 6 years old were taken carefully and transferred under cold condition to the laboratory .\nthese samples were collected from children attending day care centers in different geographical areas of mashhad , iran .\nboth plates were incubated at 37c in an atmosphere of 5% co2 for 24 hours .\nthe plates were examined and -haemolytic colonies suspected to be streptococcus pneumoniae were confirmed by optochin test and pcr for cpsa gene as described earlier ( 14 ) .\nthe optochin - susceptibility test was performed using a 6.5 mm diameter disc containing 5 mg optochin ( oxoeid ) in an atmosphere of 5% co2 .\nthe genomic dna of the bacterial isolates were extracted by dnaase tissue kit ( kiagen , tehran , iran ) .\nthe presence of rrga , pspc and lyta genes were detected among confirmed s. pneumoniae isolates by three single pcr assays .\noligonucleotides which were used as primers to amplify particular sequences of s. pneumoniae amplification conditions for lyta and pspc genes were : 94 c for 2 min , 25cycles of 94 c for 10 s , 58 c for 15 s , and 72c for1 min , followed by a final extension at 72 c for 5 min .\namplification conditions for rrga gene were : 95c for 2 min , 25cycles of 95c for 30 s , 51c for 30 s , and 72c for 90 s , followed by a final extension step at 72c for 5 min .\none amplicon from s. pneumoniae with the gene rrga was sequenced by macrogen company ( south korea ) .\nsequences were examined for identity with published sequence data from national center for biotechnology information ( ncbi ) .\na total of 260 samples from nasopharynx of healthy children under 6 years old were taken carefully and transferred under cold condition to the laboratory .\nthese samples were collected from children attending day care centers in different geographical areas of mashhad , iran .\nboth plates were incubated at 37c in an atmosphere of 5% co2 for 24 hours .\nthe plates were examined and -haemolytic colonies suspected to be streptococcus pneumoniae were confirmed by optochin test and pcr for cpsa gene as described earlier ( 14 ) .\nthe optochin - susceptibility test was performed using a 6.5 mm diameter disc containing 5 mg optochin ( oxoeid ) in an atmosphere of 5% co2 .\nthe genomic dna of the bacterial isolates were extracted by dnaase tissue kit ( kiagen , tehran , iran ) .\nthe presence of rrga , pspc and lyta genes were detected among confirmed s. pneumoniae isolates by three single pcr assays .\namplification conditions for lyta and pspc genes were : 94 c for 2 min , 25cycles of 94 c for 10 s , 58 c for 15 s , and 72c for1 min , followed by a final extension at 72 c for 5 min .\namplification conditions for rrga gene were : 95c for 2 min , 25cycles of 95c for 30 s , 51c for 30 s , and 72c for 90 s , followed by a final extension step at 72c for 5 min .\none amplicon from s. pneumoniae with the gene rrga was sequenced by macrogen company ( south korea ) .\nsequences were examined for identity with published sequence data from national center for biotechnology information ( ncbi ) .\namong 260 nasopharanx samples from healthy children under 6 years , 59 isolates were confirmed as s. pneumoniae .\ndistribution of the lyta , rrga and pspc genes among isolates of s.pneumoniae were determined .\nrrga and pspc were also found in17 ( 28.81% ) , and 2 ( 3.38% ) isolates respectively .\nfive patterns of these genes were seen among s. pneumoniae isolates : lyta ( n=33 , 55.93% ) , rrga ( n=2 , isolates , 3.38% ) , pspc ( n=1 1.69% ) , lyta+rrga ( n=16 , 27.11% ) and lyta+ rrga+ pspc ( n=1 , 1.69% ) .\nthe amplicon represented expected sequences with more than 90% identity with published data from ncbi ( genbank : ef 560634.1 ) .\nthe amplicon represented expected sequences with more than 90% identity with published data from ncbi ( genbank : ef 560634.1 ) .\nit remains unclear , however , why some children develop invasive disease , whereas in the majority of cases , colonization remains asymptomatic , a combination of bacterial virulence and host factors may be responsible ( 18 ) .\nwe studied the s. pneumoniae isolates giving special reference to identification and distribution of virulence markers such as autolysin among the isolates from nasopharynx .\nthis exercise may help in understanding the factors contributing to the pathogenicity of s. pneumoniae .\nfurther , there are numerous reports giving us increasing evidences on the role of lyta in pneumococcal pathogenesis suggesting that this might be more appropriate as vaccine antigen against s. pneumoniae infections .\nthe cpsa was used as a novel genetic marker specific for identification of s. pneumoniae and to differentiate it from the closely viridans group streptococci as well as other pneumococcus - like streptococci such as s. pseudopneumoniae ( 19 ) .\nmany virulence genes contribute to the colonization of s. pneumoniae ; however , our study only demonstrates this for pspc , rrga and lyta genes .\nthus , synergistic effect and correlation of these virulence factors is necessary for our future work .\nour results showed that most of the isolates had lyta gene ( 84.74% ) which has an important role in colonization .\nthis observation is in concordance with previous report which was showed that all of the unencapsulated isolates of s. pneumoniae were negative for lyta and psaa by pcr .\ndetection of lyta and psaa in six encapsulated isolates for which a serotype could be determined was negative ( 9 ) .\nfalse negative results were obtained by the pcr assays for these two genes may be due to mutations or sequence variation . on the other hand , lyta is essentially a rather conserved gene displaying limited genetic variation ( 11 ) . in the study of whatmore ,\n33 out of 62 isolates of s. pneumoniae were selected to represent a diverse range in terms of serotype , clinical association , and time and place of isolation .\nautolysin which was found in all strains , might appear to be a suitable target virulence , and apparently highly conserved , for inclusion in a potential vaccine ( 11 ) .\nthe pneumococcal protein lyt a is the major autolysin of s. pneumoniae , it has an important function in pathogenesis by releasing pneumolysin and plays a fundamental biological role in bacterial lysis after exposure to certain antibiotics ( 19 ) .\nit has been reported that the lyta gene has higher specificity than the pspc for identification of s. pneumoniae ( 15 , 20 ) . in our study , only 2 out of 59 isolates of s. pneumoniae ( 3.38% ) had pspc gene .\ngiven the high sequence diversity of pspc , it is unlikely that pspc alone can be a vaccine antigen to provide protection from across different pneumococcal strains ( 16 ) . \n\nit was showed that rrga is central in pilus - mediated adherence and disease , even in the absence of polymeric pilus production ( 13 ) .\nhowever , it has been demonstrated that numerous protein virulence factors are involved in the pathogenesis of pneumococcal disease ( 21 ) .\nhence , new vaccine designs are focused on the surface proteins ( e. g. , pspa and pspc ) , cytolysin , and pneumolysin ( 22 ) .\nwe concluded that the gene cpsa was specific and highly conserved among s. pneumoniae isolates which were colonized in nasopharynx . on the other hand\n, we showed that lyta gene was the most frequent genes among the s. pneumoniae isolates , and combination of rrga , lyta was the most observed pattern.thus this should allow for appropriate screening of adhesin - based vaccines to prevent infections by streptococci .", "answer": "background and objectives : many surface proteins are implicated in nasopharyngeal colonization and pathogenesis of streptococcus pneumoniae . \n some of these factors are candidate antigens for protein based vaccines . \n new vaccine designs focus on the surface proteins ( e. g. , pspa and pspc ) and also cytolysin , and pneumolysin . in this study , \n 3 key virulence genes , lyta , pspc , and rrga , which encoded surface proteins , were detected among s. pneumoniae isolates.materials and methods : a total of 260 nasopharyngeal swabs were collected from healthy children under 6 years old attending day care centers in mashhad , iran . \n isolates of s. pneumoniae were confirmed by optochin susceptibility and colony appearance and also by pcr for cpsa gene . \n the presence of lyta , pspc , and rrga genes were also detected by pcr.results:a total of 59 isolates were confirmed as s. pneumoniae . among these isolates , 50 ( 84.74% ) , 19 ( 32.20% ) , and 2 ( 3.38% ) \n were positive for lyta , rrga , and pspc genes respectively . \n the presence of these genes among s.pneumoniae isolates were as follows : 1 ) rrga , lyta , pspc ( 1 isolate ) , 2 ) rrga , lyta(17isolates ) , 3 ) pspc ( 2 isolate ) , 4 ) lyta ( 50 isolates).conclusion : cpsa gene was specific for detection of s. pneumoniae isolates which were colonized in nasopharynx . \n the lyta gene was the most frequent gene among the s. pneumoniae isolates , and combination of rrga , lyta was the most observed pattern . \n thus , it is important for future monitoring of vaccine formulation in our country .", "id": 194} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlung cancer is the main cause of mortality related to cancer in the most developed countries .\nhowever , some of the patients at initial stages of disease ( stage i , ii ) are curable .\none of the most important factors in deciding for treatment of these patients is preoperative staging with the most common form being tnm staging .\nsince surgical resection is the basic treatment of the patients at stage i , ii and is associated with good results of survival ( long - term survival of 50 - 65% ) , determining of a preoperative accurate staging method is effective in planning the treatment strategy .\nalthough for tnm staging , history , clinical examination , chest ct scan , pet scan , mediastinoscopy , and endobronchial ultrasound are routinely performed ; the results are not accurate enough for determining the stage and can be associated with over and under staging . since nowadays\nmulti - modality treatments require accurate staging ; more invasive methods in staging have been suggested . among these methods\nis vats which can more accurately evaluate t , n , and m in the patients and can prevent unneeded surgeries .\nthe aim of this study was to evaluate the role of vats in staging of non small cell lung cancer ( nsclc ) patients and detection of vats diagnosis accuracy for accurate evaluation of preoperative surgery .\nin this prospective study , all the patients with lung cancer type nsclc referred to ghaem hospital of mashhad university of medical sciences were evaluated in terms of preoperative staging ( history , clinical examination , chest ct scan , cardiac evaluation , pet , mediastinoscopy , routinely and chest or brain mri , and bone scan if needed ) .\nbefore main surgery , the patients immediately underwent vats surgery with single port and were evaluated in terms of t ( tumor extending to mediastinal elements , plural involvement ) , n ( n2 station involvement ) , and m ( satellite lesion that involved other lobe ) . if the patients had no contraindication for surgery , such as other metastatic plural involvement confirmed by pathology or satellite lesion at involved lobe confirmed by pathology or + n2 station lymph node involvement confirmed by pathology , thoracotomy by posterolateral incision\nif the patients were not candidates for surgery according to the results of vats with mentioned criteria , the surgery would be terminated and the patients were referred to oncology department for appropriate treatment .\nthe data were collected and evaluated in terms of age , sex , type of tumor pathology , method of pathology , results of ct scan , results of vats ( t : plural involvement or mediastin elements ) , n2 involvement , m1 involvement ( satellite lesion of involved lobe ) , results of main thoracotomy surgery , type of pulmonary resection , and vats diagnosing accuracy . to evaluate mediastinal extension in vats ,\nthe patients were divided into three groups based on the results of preoperative ct scan , and vats . \n\npatients with confirmatory ct scan findingpatients without confirmatory ct scan findingimpossible to confirm ct scan finding . \n patients with\nconfirmatory ct scan finding patients without confirmatory ct scan finding impossible to confirm ct scan finding .\ndata were statistically analyzed by spss software version 11.5 and to evaluate vats diagnosing accuracy , we also used distribution , mean , and standard deviation for quantitative variables and frequency for qualitative variables .\ndiagnostic accuracy was estimated by table of test validity , for calculating diagnostic accuracy we devided the summation of true positive and true negative by the number of total cases .\nmediastinoscopy was performed with standard technique in the patients at supine position under general anaesthesia by a small incision in supra sternal notch .\nsampling was classically performed for all patients from ( 2l , 2r , 4l , 4r , 7 ) areas , and were sent for pathology evaluation .\nvats was also performed immediately before main surgery by double lumen ventilation and evaluation was performed by single port vats ( in terms of plural involvement , tumoral adhesion satellite lesion , n2 station ln involvement ) ; in case of any doubt , sampling was performed and were sent for frozen section and decision was made based on the results of pathology .\nif there was no contra - indication for main surgery , final surgery was performed by standard posterolateral thoracotomy incision and open technique .\nmediastinoscopy was performed with standard technique in the patients at supine position under general anaesthesia by a small incision in supra sternal notch .\nsampling was classically performed for all patients from ( 2l , 2r , 4l , 4r , 7 ) areas , and were sent for pathology evaluation .\nvats was also performed immediately before main surgery by double lumen ventilation and evaluation was performed by single port vats ( in terms of plural involvement , tumoral adhesion satellite lesion , n2 station ln involvement ) ; in case of any doubt , sampling was performed and were sent for frozen section and decision was made based on the results of pathology .\nif there was no contra - indication for main surgery , final surgery was performed by standard posterolateral thoracotomy incision and open technique .\na total of 40 patients entered the study with ratio of m / f = 21/19 .\nmean age of the patients was 57.2 16.64 yrs ( min 15 and max 65 yrs ) .\nother symptoms were hemoptysis in 27 patients ( 67.5% ) and exertion dyspnea in 33 cases ( 82.5% ) and pleuritic chest pain in 17 cases ( 42.5% ) . in the preoperative evaluation ,\nimportant findings in ct scan with iv contrast were as follows : observation of mass lesion in 40 patients ( 100% ) , observation of hilar or mediastinal lymphadenopathy in 17 cases ( 42.5% ) , and observation of effusion in 9 cases ( 22.5% ) which cytology of pleural liquid and pleural biopsy were negative in all of these 9 patients .\nthere was the possibility of involvement of mediastinal elements ( direct extension ) ( 22.5% ) .\nflexible bronchoscopy and bal were performed for all patients before surgery and 29 patients ( 72.5% ) had endobronchial mass and biopsy was performed for them . for 11 cases ( 27.5% ) because of peripherally located lesions and no endobronchial mass , tissue samples were taken by the method of ttnb under the guide of ct scan .\nall the patients underwent standard mediastinoscopy with samples from ( 2l , 2r , 4l , 4r , 7 ) areas and the results of pathology were negative in all .\nthe patients who were candidates for main surgery underwent vats immediately before final surgery and the results of vats immediately before final surgery were unresectable tumors in 6 patients ( 3 cases ( 7.5% ) due to seeding plural metastasis confirmed by pathology , 2 cases ( 5% ) due to n2 station ( one case in station 4 and one cases in station 9 ) , and one case ( 2.5% ) due to satellite mass that involved other lobe ) .\nthe remainder 34 patients ( 85% ) underwent thoracotomy immediately after vats and surgical resection was performed successfully in 31 cases ( 77.5% ) , but in 3 cases ( 7.5% ) due to adhesion of tumor to hilum , tumor was not resectable .\ntable 1 shows type of surgical resection and the frequency of pulmonary resection in 31 patients underwent surgery .\ntable 2 shows the frequency of pathological results . in terms of diagnosing accuracy of vats for evaluation of tumor direct extension based on the results of ct scan , in 9 patients ( 22.5% )\nthere was report by ct scan that involvement of hillum of the lung and mediastin elements ; vats showed that in 5 cases ( 12.5% ) , tumor was resectable ( not confirmed by ct scan finding ) , and in 4 cases ( 10% ) , we could nt determine whether tumor was resectable or not ( impossible to confirm ct scan finding ) . frequency and type of pulmonary resection frequency and type of pathological result based on the final results of surgery , all the patients in the group of non confirmatory ct scan findings ) ( 5 cases = 12.5% ) had successful pulmonary resection . in 4 cases ( 10% ) which we could nt determine whether tumor was resectable or not ( impossible to confirm ct scan finding ) , tumor was resectable in 1 case ( 2.5% ) and not resectable in 3 cases ( 7.5% ) . according to the above results , vats diagnosing accuracy for accurate evaluation of preoperative surgery was 92.5% .\nperforming tnm staging in lung cancer type nsclc is important for deciding the patients treatment and prognosis .\none of the criteria for determining preoperative staging is t and m stage which can be evaluated by bronchoscopy , ct scan , mri , and needle biopsy .\nnevertheless , some of the patients which are considered to be at stage iiib can be in lower stages and the patients which are estimated to be at stage i and stage ii can be at higher stage and more accurate evaluation is needed .\nthe study of passlick and co - workers reported that vats was a suitable method in evaluation of pleural involvement , finding lymph node ( n2 ) , or pulmonary ( n1 ) metastases on the other side .\nthey even reported that in patients with effusion and negative cytology , vats can confirm plural spreading in 60% of cases and recommended performing vats before thoracotomy for prevention of un - needed thoracotomies .\nthe main problem in treatment planning of these patients is evaluation of n stage , since an important factor for treatment planning and survival estimation is n2 or 3 stations involvement .\nde langen , et al . performed a study in 2006 about evaluation of n staging .\nthey attempted to answer the question of whether lymph node size observed in ct scan is a criterion for performing complementary methods to obtain tissue samples .\nthey showed that it is better for all of these patients to undergo fdg - pet after ct scan and divided the patients into three groups : group i : 10 - 15 mm , group ii : 16 - 20 mm , group iii : > 20 mm .\nthey found that the patients with tumor size : 10 - 15 mm with negative pet ( the possibility of lymph metastasis is < 5% ) were not candidates for other methods for obtaining tissue samples ; other patients with either positive or negative pet scans were candidates for mediastinoscopy .\nanother study by bill , et al . in 2009 showed that lymph node size and the results of negative pet were not accurate for evaluation of the patients in terms of n2 stage involvement and they recommended routinely performing of mediastinoscopy for all patients .\nstandard mediastinoscopy is a gold standard method and is confirmed by the most researchers for all patients with lung cancer , and tissue sampling should be performed in 5 areas : ( 2l , 2r , 4l , 4r , 7 ) ; for increasing the diagnosing accuracy of mediastinoscopy , other methods are mentioned .\nblock and colleagues in 2010 reported that performing endobronchial ultrasound is a complementary method in n staging and declared that biopsy of all stations is performable by ebu and it is better to perform two biopsies of each station to increase diagnosing accuracy .\nin study performed by gomez et al . using ebus with needle biopsy is considered helpful to diagnose central lymphadenopathy .\nkuzdza , et al . in 2007 mentioned that performing transcervical extended mediastinal lymphadenectomy is a suitable method in mediastinoscopy for n evaluation . the results of this method were similar to mediastinoscopy and the rate of invasion was also similar to mediastinoscopy .\nof course , these studies were limited and the more studies are required . to increase diagnosing accuracy ,\nvats is usually combined with mediastinoscopy to cover the areas which mediastinoscopy can not observe .\nsince vats can perform sampling of lymph nodes in these areas , it is a good replacement for extended mediastinoscopy .\nof course , standard mediastinoscopy has sensitivity of 81% and specificity of 91% and can not evaluate some patients . a study performed by witte , et al . on combination of mediastinoscopy with vats\nto increase diagnosing accuracy showed that this combination was helpful to increase diagnosing accuracy of standard mediastinoscopy . among accurate\ndiagnosing methods in n2 station is dye injection in tumor and evaluation of sentinel lymph nodes by vats . in the study of yamashita , et al . in 2011\n, they could find sentinel lymph nodes by injection of indocyanine green fluorescence image guide surgery and recommended to dissect the lymph node if they were not involved ; diagnosing accuracy of this method was 80.7% .\nsince treatment planning and prognosis determination require accurate evaluation of tnm staging , it seems that preoperative vats can help to determine tnm staging and prevents unnecessary thoracotomy in some patients and we recommend this method .\nhowever , the numbers of the patients in our study are limited and a definite conclusion needs further studies .", "answer": "introduction : since determining of prognosis and treatment method is related to accurate evaluation of tnm staging of non small cell lung cancer ( nsclc ) , we aimed to evaluate the role of video - assisted thoracic surgery ( vats ) in staging of nsclc.materials and methods : this study was performed on 40 patients with nsclc who had undergone preoperative staging and were candidate for curative surgery between 2008 - 2010 . they underwent vats immediately before the surgery . after performing vats , the patients underwent thoracotomy by posterolateral incision unless any criteria of inoperability were present . diagnostic accuracy of vats for confirmation or modification of preoperative \n staging was evaluated.results:m/f ratio was 21/19 . \n mean age of the patients was 57.2 16.64 yrs . \n the most common symptom was coughing in 90% of patients . \n 72.5% of the patients had endobronchial mass and only for 27.5% tissue sample was obtained by transthoracic needle biopsy ( ttnb ) method . after performing vats , \n 6 patients were excluded from surgery ( 3 cases ( 7.5% ) due to seeding plural metastasis , 2 cases ( 5% ) due to n2 involvement and one case ( 2.5% ) due to satellite lesion in other lobes ) . \n other 34 patients underwent surgery . \n surgical resection was performed successfully in 31 cases ( 77.5% ) , but in 3 cases ( 7.5% ) due to adhesion to hillum of the lung tumor was not resectable . according to the above results , vats diagnosing accuracy was 92.5%.conclusion : vats can help to determine tnm staging and prevent unnecessary thoracotomy in some patients and we recommend this method for accurate staging of nsclc .", "id": 195} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalzheimer s disease ( ad ) is a progressive and the most prominent old - age debilitating disease which had a notable epidemic growth in recent years . according to statistical analyses\n, it is estimated that the number of people suffering from ad will double every twenty years ; and by 2050 , the number of sufferers from ad in the world would reach 115 million ( 1 , 2 ) .\none - eighth of people aged 65 and older and half of people aged 85 and older were diagnosed with ad , approximately ; its death toll from 2000 to 2008 has increased by 66% ( 3 ) .\nthe costs for this disease are so high that one percent of global gdp is spent on ad s consequences ( 4 ) .\ndiagnosed patient with ad usually dies after 5 to 7 years ( 2 ) . in iranian traditional medicine ( itm )\nmanuscripts , diseases in which forgetfulness is the main symptom are categorized under nesyan label . in itm manuscripts ,\none of the types of nesyan which originates from coldness and dryness of the brain has the same symptoms as ad . forgetting recent events and remembering old happenings , cognitive disturbance , problems in constant talking ( language disability ) , and insomnia are of its most important signs ( 5 , 6 ) which are similar to ad s according to nincds - adrda criterion ( 7 ) .\nitm takes nourishment as one of the six pillars of health ( 8 , 9 ) ; therefore , itm manuscripts have dedicated a considerable part of their content to nutritional recommendations . in the first volume of canon of medicine , avicenna ( 970 - 1051 a.d . ) , the great persian scholar , described those in detail ( 10 ) .\nhe urged elderly people not to take foods producing black bile ( sowd ) such as lentil , eggplant , beef , dried meat , and salted foods ; and phlegmatic foods such as fish , watermelon , melon , and cucumber .\non the other hand , taking milk , shirberenj ( an iranian dish consists of milk , rice , sugar , and rosewater ) , honey milk , and milk with ginger are recommended .\napart from preventive recommendations , nutritional therapeutic recommendations are included to boost medication and shorten illness - period ; and nesyan is no exception .\nmuhammad ibn zakariy rz ( rhazes ) ( 865 - 925 a.d . ) , another great persian scholar , in his book al - hawi recommended to have poultry ( such as chicken , dull - yellow partridge , hoopoe , pheasant , and sparrow meat ) , their brains , and yolks for people affected to nesyan . at the same time\nthe patients were prohibited from having beef , mutton , goat meat , camel meat , and rabbit meat because they produce black bile ; and fish as well for producing phlegm ( balgham ) . moreover , having nuts such as almond , hazelnut , coconut , and walnut were recommended ( 12 ) .\nit is worth mentioning that some other persian scholars such as aghili korasani and chishti had the same idea as rhazes ( 5 , 6 ) .\nthere have been remarkable either observational or experimental studies on the role of diet and nutrients in prevention and treatment of dementia , especially ad .\nstudies on effects of different kinds of fat such as saturated fatty - acids ( sfa ) , unsaturated fatty - acids ( ufa ) , and cholesterol on ad have been conducted recently .\nunsaturated fatty - acids and cholesterol play an important role in the brain ; 60 percent of dry weight of the brain is consisted of fat which 20% of it is of unsatu - rated fatty - acids ( 13 ) .\nalthough the brain is only 2% of the total body mass , it carries 25% of cholesterol of the whole body ( 14 ) . in the light of\nthe fact that most of the brain is consisted of fat and it uses nutrients as other organs , types and amounts of fat consumption could be vitally important in the brain s health .\nstudying multi - nutrient diets ( instead of one or more nutrients ) has a notable importance .\none of the multi - nutrient diets which have been frequently studied is the mediterranean diet ( table 1 ) ( 15 ) .\nstudies have shown that it has preventive effect on ad ( 16 , 17 ) .\ntaking types of fat into consideration , this diet has a great deal of ufas and lesser amounts of sfas and cholesterol .\nufas positive impact has been reported in several other researches ( 18 ) . while the results of studies on therapeutic role of ufas ( especially omega-3 ) on ad are controversial ( 19 , 20 ) , ufas\nmulti - nutrient diets like the mediterranean diet which contains high levels of ufas have abated the incidence of ad ( 16 , 17 ) ; the abatement is 13% according to sofi et al .\nstudy on the relationship between the mediterranean diet and health status in 2008 ( 17 ) . about cholesterol\n, it plays a vital role in cell membranes , yet its functions in neurons are more prominent .\ncholesterol is amassed within lipid rafts in the neuronal cell membrane and is involved in the formation and maintenance of synaptic connections ( 21 ) . several studies on the effect of cholesterol on ad had ambiguous results . according to the importance of diets\nespecially fats - in ad , this study attempted to analyze the fat content of itm recommended diet for nesyan ( itm equivalent of alzheimer s disease ) . since traditional physicians used to recommend distinctive diets based on their own clinical experiences , analyzing these diets would eventuate in new nutritional regimen to improve ad sufferers quality of life .\nin order to study the traditional recommended diet for nesyan , itm prominent books including al - hawi ( rhazes , 10th century ) , canon of medicine ( avicenna , 11th century ) , zakhire - ye - khawrazmshahi ( jorjani , 12th century ) , kholasat - ul - hekma ( aqilikhorasani , 18th century ) , and exir - e - azam ( chishti , 19th century ) were searched for recommended and abstinent foods and diets traditionally prescribed for patients afflicted by senescence and/or nesyan ( 5 , 8 , 11 , 12 , 22 ) . to quantify the results ,\nthe content of fatty components of each food ( including polyunsatu - rated ( pufa ) , monounsaturated ( mufa ) , and saturated fatty acids ( sfa ) and also cholesterol ) were extracted from the database of the department of agriculture of the usa ( usda ) ( 23 ) .\nthe content of fatty elements per 100 gr of each recommended food was compared with that of the abstinences and statistically analyzed by mann - whitney test via spss ( version 16 ) .\nabout the diet , the sum of the nutrients of recommended and abstinent diets for daily consumption was also measured .\nad dietary recommendations and abstinences which currently published in medical journals were also searched via scopus .\nfinally , traditional and new dietary suggestions were compared with each other and the results presented as tables and figures .\nthe results show that the recommended foods ( presented in the first column of table 2 ) are fattier than the abstinent ones ( presented in the first column of table 3 ) ( p<0.001 ) .\nthere are also meaningful differences between unsaturated fatty acids ( p<0.001 ) , saturated fatty acids ( p<0.001 ) , and cholesterol ( p<0.05 ) of recommended foods and abstinent foods ( fig .\nthese foods form recommended and abstinent diets for nesyan . this recommended diet is fattier than the abstinent diet ( 4.5 times ) ( see the last row of table 2 and 3 ) ; polyunsaturated fatty acids of recommended diet\nit is the same story for monounsaturated fatty acids and cholesterol ( 11 and 1.4 times more than abstinent diet , respectively ) ( fig .\n2 ) . fatty components in 100 gr of each food traditionally recommended or forbidden for people afflicted by nesyan . *\nerror bars indicate sem comparison between nutritional factors of recommended and abstinent diet in nesyan the results of searching scopus database show that recent studies emphasize on diets with high amounts of unsaturated fatty acids for ad sufferers .\na considerable number of papers but not all of them - emphasizes on probable positive role of cholesterol on ad .\nnutritional factors of daily diet recommended for patients affected with nesyan in iranian traditional medicine .\nthe last row of the table presents the amounts of nutrients in daily recommended diet nutritional factors of daily diet forbidden for patients affected with nesyan in iranian traditional medicine .\nthe last row of the table presents the amounts of nutrients in daily abstinent diet .\niranian traditional medicine has nutritional recommendations to help curing nesyan ( ad equivalent in traditional medicine ) . in this study , evaluating the ingredients of the recommended foods highlights that it is ufas - rich because of having nuts .\nthe types of meat in the recommendations are mostly poultry ( chicken , pheasant , and sparrow ) ; their remark is their greater amount of cholesterol compared to the abstinences .\nsome recent studies substantiate that cholesterol is a boost to improve memory function ( 24 , 25 ) .\nwhen cholesterol is consumed with ufas , it will turn into hdl ( 26 , 27 ) . in 2004 ,\nreitz and colleagues have concluded that there is no connection between serum cholesterol level and ad ( 28 ) .\nhowever , some other studies have shown that the higher the serum cholesterol level in the elderly , the better memory functions ( 24 , 25 ) .\nsome studies also have shown the decline in serum total cholesterol levels is associated with increased dementia risk ( 29 , 30 ) .\nfurthermore , in a cohort study conducted on 1130 people ( published 2010 ) , reitz et al .\nconclude that high hdl levels in elderly individuals may be associated with a decreased rate of ad ( 31 ) .\nprior to reitz , singh - manoux and colleagues ( 2008 ) indicated that a low level of hdl could be considered as a risk factor of memory dysfunction ( 32 ) .\nbear in mind , there has been no study on hdl destructive effect on ad , so far ( 33 ) .\ntherefore , prescribing more amounts of cholesterol along with ufas in itm is in accordance with recent studies . on the other side ,\nrecent studies have shown that cholesterol and all of its precursors in cerebrospinal fluid ( csf ) and its precursorslanosterol , lathosterol , and desmosterol in plasma abate in ad sufferers ( 34 , 35 ) . in 2010 , klsch et al . determined csf and plasma levels of cholesterol and its precursors in ad diagnosed people compared to those of healthy individuals .\nthe results showed that csf levels of cholesterol and all of its precursors and also plasma levels of two of the precursors named lanosterol and lathosterol are lower in ad diagnosed people than those of healthy individuals ( 34 ) .\nsato et al . showed in 2012 that plasma levels of desmosterol , another precursor of cholesterol , are also lower in alzheimer s sufferers than the levels in healthy ones ( 35 ) .\nthis casts doubt whether the cholesterol reducing agents have preventive effect on ad or not .\nthere are some studies highlighting that cholesterol reducing agents such as statins are ineffective on ad incidence ( 36 , 37 ) . in a prospective study conducted by zandi et al .\n( 2005 ) on 5000 elderly people in the usa , the relationship between statins consumption and the onset of dementia or ad has been violated ( 36 ) . along the lines of zandi\ns study , mcguinness and colleagues ( 2009 ) co - evaluated two randomized double blind clinical trials containing 26 thousand participants which resulted that there is no relationship between statins consumption and the risk of ad incidence ( 37 ) .\nalso , reduction in serum total cholesterol could be considered as a risk factor of dementia in the elderly ( 29 , 30 ) .\nthere are other ingredients in the abstinences which are not considerable in having fats and cholesterol .\npumpkin , lettuce , melon , garlic , onion , cabbage , beans , broad beans , and mushroom are of its examples .\naccording to iranian cuisine in the past , there were foods in itm that have no place in eating habit nowadays ; so there is not much information about them .\nhoopoe , lark , dull - yellow partridge meat and their brain are of the examples .\nthis diet contains high amounts of unsaturated fatty acids and cholesterol to boost treatment of nesyan ( traditional equivalent of alzheimer disease ) .\naccording to new scientific findings , this kind of diet could be useful as a complementary therapy of alzheimer disease .\nethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .", "answer": "abstractbackgrounddietary notifications have been introduced recently for alzheimer disease ( ad ) . in iranian old medical manuscripts , there are some nutritional recommendations related to nesyan ( ad equivalent ) . \n the aim of this article was to compare dietary recommendations of iranian traditional medicine ( itm ) with novel medical outcomes.methods1 ) searching for dietary recommendations and abstinences described in itm credible manuscripts ; 2 ) extracting fatty components of itm diet according to the database of the department of agriculture of the usa ; 3 ) statistical analysis of fatty elements of traditionally recommended foods via mann - whitney test in comparison with elements of the abstinent ones ; 4 ) searching for ad dietary recommendations and abstinences which currently published in medical journals ; 5 ) comparing traditional and new dietary suggestions with each other.results1 ) traditionally recommended foods are fattier than abstinent ones ( p<0.001 ) . \n there are meaningful differences between unsaturated fatty acids ( ufas ) ( p<0.001 ) , saturated fatty acids ( p<0.001 ) , and cholesterol ( p<0.05 ) of recommended foods and abstinent ones . \n 2 ) traditionally recommended diet is also fattier than the abstinent diet ( 4.5 times ) ; ufas of the recommended diet is 11 times more than that of the abstinent one ; it is the same story for cholesterol ( 1.4 times ) ; 3 ) recent studies show that diets with high amounts of ufas have positive effects on ad ; a considerable number of papers emphasizes on probable positive role of cholesterol on ad ; 4 ) traditional recommended diet is in agreement with recent studies.conclusionitm recommended diet which is full of unsaturated fatty acids and cholesterol can be utilized for complementary treatment of ad .", "id": 196} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbicycle riding is popular throughout the world for transportation , recreation , sports , and health - related benefits .\n53% are men . in korea , according to the needs of the times , such as economic development and increased leisure time , a trend for preferring environmentally friendly sports , and growing interest in health and well - being , the awareness of cycling as a leisure sport has recently increased .\nthere were 24,406 recreational bicycle riders in 911 bicycle clubs in korea as of january 2010 .\nbicycling is an ideal form of aerobic , nonimpact exercise with established protective cardiovascular effects and a beneficial influence on the risk of hypertension , diabetes , and stroke .\nalthough there are controversies about changes to the genitourinary system in subjects who cycle , bicycle riding has been known as a common source of acute traumatic injuries as well as overuse injuries [ 4 - 6 ] .\nbicycling studies suggest perineal trauma , pressure , or both may have a role in these genitourinary hazards .\nmany of them directly affect the genitourinary tract , causing genital numbness , erectile dysfunction ( ed ) , priapism , infertility , hematuria , and effects on serum prostate - specific antigen ( psa ) levels .\nmany healthy recreational bicycle riders have questioned urologists about the relationship between bicycle riding and prostate - related lower urinary tract symptoms ( luts ) .\nbut to the best of our knowledge , there has been no study of luts in male recreational bicyclists . with this study ,\nour goal was to evaluate the impact of bicycle riding on luts and sexual dysfunction in men with the use of amateur marathoners as a control group of physically equivalent individuals with a low level of perineal pressure or trauma .\na total of 22 healthy male amateur bicycle riders from two bicycling clubs in jeonju , korea , were studied .\nthe recruitment criteria were age between 40 and 50 , bicycling period of more than 1 year before the study , three or more times of cycling per week , and 30 minutes or more of cycling duration per time .\nthe controls were 17 healthy male marathoners from an amateur marathon club in jeonju , korea .\n, all subjects were informed about the experimental procedures , which were in accordance with the ethical standards of chonbuk national university hospital , and were required to give written informed consent .\nthe evaluation contained a study questionnaire assessing sports participation habits , urological and medical history , the international prostate symptom score ( ipss ) , the international index of erectile function ( iief ) , the international continence society ( ics ) male questionnaire - short form , the overactive bladder symptom score ( oabss ) , and the premature ejaculation diagnostic tool ( pedt ) .\nan ipss of more than 7 defined the voiding dysfunction ( vd ) group , and erectile ed was defined as a score of 21 or less on the iief-5 , an abridged 5-item version of the iief-15 , which ensured identification of the mildest forms of ed .\nfurthermore , we examined serum total prostate - specific antigen ( tpsa ) , free prostate - specific antigen ( fpsa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound ( trus , b&k medical , herlev , denmark ) of the prostate in all subjects .\nchicago , il , usa ) . to test differences between the two groups in serum tpsa , fpsa , uroflowmetric values , pvr urine volume , calculated volume of the prostate using trus , and the total or subscale score of each questionnaire , we used independent - sample t - tests with statistical significance as p<0.05 .\nalso , we compared the two groups for the prevalence of vd and ed by using the chi - square or fisher 's exact tests with statistical significance as p<0.05 .\na total of 22 healthy male amateur bicycle riders from two bicycling clubs in jeonju , korea , were studied .\nthe recruitment criteria were age between 40 and 50 , bicycling period of more than 1 year before the study , three or more times of cycling per week , and 30 minutes or more of cycling duration per time .\nthe controls were 17 healthy male marathoners from an amateur marathon club in jeonju , korea .\n, all subjects were informed about the experimental procedures , which were in accordance with the ethical standards of chonbuk national university hospital , and were required to give written informed consent .\nthe evaluation contained a study questionnaire assessing sports participation habits , urological and medical history , the international prostate symptom score ( ipss ) , the international index of erectile function ( iief ) , the international continence society ( ics ) male questionnaire - short form , the overactive bladder symptom score ( oabss ) , and the premature ejaculation diagnostic tool ( pedt ) .\nan ipss of more than 7 defined the voiding dysfunction ( vd ) group , and erectile ed was defined as a score of 21 or less on the iief-5 , an abridged 5-item version of the iief-15 , which ensured identification of the mildest forms of ed .\nfurthermore , we examined serum total prostate - specific antigen ( tpsa ) , free prostate - specific antigen ( fpsa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound ( trus , b&k medical , herlev , denmark ) of the prostate in all subjects .\nchicago , il , usa ) . to test differences between the two groups in serum tpsa , fpsa , uroflowmetric values , pvr urine volume , calculated volume of the prostate using trus , and the total or subscale score of each questionnaire , we used independent - sample t - tests with statistical significance as p<0.05 .\nalso , we compared the two groups for the prevalence of vd and ed by using the chi - square or fisher 's exact tests with statistical significance as p<0.05 .\na total of 22 recreational bicyclists ranging in age from 42 to 57 years completed the questionnaires and were included in the assessment .\nthe riders had cycled for a period of 1 to 10 years ( range , 4.052.04 years ) , 3 to 6 times per a week ( range , 4.231.19 times ) , and with 60 to 240 minutes of cycling duration per time ( range , 9159 minutes ) .\nthe subjects ' body mass index ( bmi ) ranged from 22.8 to 34.6 kg / m ( range , 25.92.67 kg / m ) .\nthere were no significant differences between the two groups in age , bmi , comorbidities , or exercise habits ( table 1 ) .\nthere were no significant differences in the total and subscale scores of the ipss between the two groups .\nthe prevalence of vd on the basis of the ipss was not significantly different between the two groups ( 8/22 vs. 4/17 , p=0.494 ) .\nthere were no significant differences in total and subscale scores of the iief between the two groups .\nthe prevalence of ed based on the iief was not significantly different between the two groups ( 11/22 vs. 10/17 , p=0.748 ) .\nalso , we found no statistical differences in other questionnaires such as the oabss , ics male questionnaire - short form , and pedt ( table 2 ) .\nas shown in table 3 , there were no significant differences between the two groups regarding uroflowmetric parameters such as peak urinary flow rate ( qmax ) , voided urine volume , or pvr urine volume . in all subjects ,\nprevoid urine volume was at least 150 ml and voided urine volume was at least 125 ml . in the cyclists ,\nthe mean calculated volume of the prostate by trus was 23.32 cc and there was no statistically significant difference between the two groups ( 23.32 vs. 23.71 , p=0.848 ) .\nalso , the serum tpsa level was within the normal range in all subjects and there was no significant difference between the two groups ( 0.800 vs. 0.888 , p=0.470 ) . the prevalence of a significantly low qmax , excess pvr , or benign prostatic hyperplasia was not significantly different between the two groups ( table 3 ) .\nthe most common bicycling - associated urogenital problems are nerve entrapment syndromes presenting as genitalia numbness , which was reported in 50% to 90% of cyclists , followed by erectile dysfunction in 13% to 24% .\nother less common symptoms include priapism , penile thrombosis , infertility , hematuria , torsion of the spermatic cord , prostatitis , perineal nodular induration , and elevated psa , which are reported only sporadically .\nbicycle riding is used throughout the world for well - known exercise , fitness , and recreational benefits . as such\n, it is not surprising that these statements have created much controversy . in our study population , we investigated in particular the relationship between bicycle riding and luts or sexual dysfunction by use of questionnaires ; thus , we did not ask the study group about complications such as genitalia numbness . to date\nrecently , saka et al reported that bicycle riding has no impact on serum psa levels and urinary flow parameters .\nthe goal of their study was to investigate whether professional bicycle riding altered plasma concentration of tpsa , fpsa , percent free psa ( f / t psa ) , and urinary flow parameters in healthy men .\nwe present a cross - sectional study of the effects of bicycle riding , a sport with perineal impact , on genitourinary function in men . in our study ,\nthe subjects were amateur recreational bicycle riders from clubs , and we aimed to find any hazards of bicycle riding in male luts or sexual dysfunction .\nour hypothesis was that if bicycle riding had any impact on the genitourinary tract there would be significant differences in genitourinary functional parameters between a regular long - term bicycle - riding group and control group of physically equivalent individuals with a low level of perineal pressure or trauma , such as a regular long - term marathon running group .\nhowever , there were no significant differences between the two groups regarding the questionnaires , uroflowmetric parameters , pvr urine volume , prostate volume , or serum psa level .\nthus , we found the inverse of our hypothesis : that bicycle riding may have no hazardous impact on genitourinary health in recreational male bicycle riders .\nthe prevalence of luts or vd as defined by an ipss of 8 was not significantly different between the two groups .\nphysical activity has been documented to be protective against luts in previous studies , and the perineal impact of bicycle riding does not seem to offset that effect .\nmany of the bicyclists enrolled were very energetic and confident of their health , and there were no significant differences in the uroflowmetric analysis results , trus - measured prostate volume , or serum psa level .\nbicycle - riding - induced perineal impacts do not have enough influence on the prostate mechanically or physiologically .\nprevious reports about the effect of bicycling on serum psa concentrations were not conclusive , but in recent studies the dominant finding was that there was no statistically or clinically significant change in psa levels regardless of cycling [ 7 - 12 ] .\nno other published data have compared questionnaires evaluating luts , uroflowmetric analysis results , or trus - measured prostate volume of regular long - term amateur bicycle riders with a control group of physically equivalent individuals with a low level of perineal pressure or trauma such as a regular long - term runner group .\nprevious studies have reported an association between bicycling and sexual dysfunction , but those studies were based on biological measurements such as penile blood flow , focused on sexual dysfunction after prolonged exposure to perineal impact , or suggested a trend but no strong association .\nthe results of our study support the observation of others that bicycle riding has no effect on luts and male sexual function .\nfirst , the cross - sectional study structure may have affected the validity of the results .\nwe did not collect baseline data about luts and sexual dysfunction parameters before activity from either group .\nwe implemented a cross - sectional study design as an efficient and cost - effective investigation to perform a preliminary exploration for an association with the potential to generate additional hypotheses for more structured research .\nsecond , the small number of subjects may have introduced some selection bias into the results .\nhowever , we suspect that the influence of the bias may be weak because almost all of the 5th and 6th decades of each club participated in our study . we plan to do vertical , annual follow - up studies of the subjects .\nthe fact that the results of our study are consistent with data from other studies in similar sports supports the validity of our results and decreases the chance of systemic errors .\nmore assessment of the effect of bicycle riding on the human pelvic anatomy and genitourinary complaints is warranted to further validate the results of this study .\nconcern about bicycle riding as a leisure sport has recently increased as many urological outpatients and healthy recreational bicyclists have questioned urologists about the relationship between bicycle riding and prostate - related luts and sexual dysfunction . in our opinion , bicycle riding seems to have no statistically measurable effect on luts or sexual functioning in men , at least in amateur recreational bicyclists .\nthere is a need for further large - scale research on this subject and study of the underlying mechanisms leading to cycling - related luts and sexual dysfunction .", "answer": "purposethis study was designed to determine whether men who engaged in recreational bicycle riding are more likely to be affected by lower urinary tract symptoms ( luts ) and sexual dysfunction than are man who exercised by amateur marathon running with less perineal impact.materials and methodsa total of 22 healthy male amateur bicyclists and 17 healthy male amateur marathoners were enrolled in the study . \n we evaluated questionnaires including the international prostate symptom score ( ipss ) and the international index of erectile function ( iief ) , serum prostate - specific antigen ( psa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound of the prostate in all subjects . \n we also compared the prevalence of urination disorders ( ud ) and erectile dysfunction ( ed).resultsthere were no significant differences between the two groups in age , body mass index , comorbidities , or exercise habits ( p>0.05 ) . \n mean total and subscale scores of the ipss and iief and the prevalence of ud ( 8/22 vs. 4/17 , p=0.494 ) and ed ( 11/22 vs. 10/17 , p=0.748 ) were not significantly different between the two groups . \n also , there were no significant differences between the two groups in uroflowmetric parameters such as peak urinary flow rates , voided urine volume , pvr urine volume , prostate volume , or serum psa level.conclusionsbicycle riding seems to have no measurable hazardous effect on voiding function or sexual function in men who cycled recreationally .", "id": 197} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwarfarin is the most commonly used oral anticoagulant both for prophylaxis as well as treatment for arterial and venous thromboembolic conditions .\nit has a narrow therapeutic index and is metabolized by hepatic cytochrome p450 2c9 enzyme ( cyp2c9 ) .\nvarious polymorphisms exist in the gene that code for cyp2c9 , of which * 1 is the wild form expressing normal activity . amongst the variants , * 2 and * 3 are more common than the rest and exhibit lesser enzymatic activity .\nthe anticoagulant effect of warfarin is measured by prothrombin time - international normalized ratio ( pt - inr ) .\nwarfarin exerts its anticoagulant effect by reducing the regeneration of active vitamin k through inhibition of vitamin k epoxide reductase , encoded by vitamin k epoxide reductase complex subunit 1 gene ( vkorc1 ) .\nincreased risk of deranged inr or bleeding has been reported in patients harboring mutant form of either cyp2c9 or vkorc1 .\nthis case report describes a patient on low - dose warfarin , who succumbed to a subdural hematoma and was found to have polymorphic cyp2c9 ( * 1/*3 ) .\na 49-year - old male patient , who was a known case of superior sagittal sinus thrombosis for the past 8 years on tablet warfarin 2.5 mg every night , was brought to the hospital unconscious .\nthe patient was non - compliant in not following up with his physician nor did he check his pt - inr levels regularly for the past 1 year .\nthe patient 's relative , however , maintained that the patient was regular in taking the prescribed dose of warfarin ( 2.5 mg ) every night . on physical examination\n, he was found to be unconscious ( glasgow coma scale score of 3 ) , pulse was feeble and the blood pressure was not recordable .\na plain computed tomography ( ct ) brain revealed 24.2 mm hyperdense cresentic subdural hematoma in left fronto - temporo - parieto - occipital region with subfalcine extension and midline shift [ figure 1 ] .\nhis pt - inr was found to be 9 [ normal ( in the absence of anticoagulation therapy ) is 1 and it has to be maintained between 2 and 3 for an appropriate therapeutic effect for warfarin ] .\nfresh frozen plasma was initiated at a dose of 15 ml / kg / day .\nblood ( 5 ml ) was collected from the patient and genotyping was done for both cyp2c9 and vkorc1 .\ncyp2c9 was found to be polymorphic for * 3 ( * 1/*3 ) and vkorc1 was found to be wild - type ( normal ) .\nplain ct brain revealing 24.2 mm hyperdense cresentic subdural hematoma ( red arrow ) in left fronto - temporo - parieto - occipital region\npharmacogenetics is the study of genetic influence on inter - individual variation in the response of a drug .\npharmacogenetics has been shown to be of value in detecting an optimal response as well as in preventing adverse reactions following drugs such as warfarin , clopidogrel , and phenytoin .\nwarfarin is metabolized by cyp2c9 and over 30 polymorphic alleles have been identified in the gene coding for cyp2c9 .\nthe wild form of the gene is * 1 and the most common polymorphic forms include * 2 and * 3 .\nallelic frequency of cyp2c9 * 2 and * 3 in various populations including indians were found to be in the range of 0 - 20% .\na recent systematic review concluded that in comparison to the patients with cyp2c9 * 1/*1 genotype , the cyp2c9 * 1/*2 , cyp2c9 * 1/*3 , cyp2c9 * 2/*2 , cyp2c9 * 2/*3 , and cyp2c9 * 3/*3 patients required warfarin doses that were 19.6 , 33.7 , 36.0 , 56.7 , and 78.1% lower , respectively .\nsimilarly , in the vkorc1 gene , two alleles have been identified in vkorc1 namely g and a. patients with gg ( wild type ) are resistant requiring a higher dose of the drug whereas aa are sensitive requiring a lesser dose and ga requires intermediate .\na randomized clinical trial has also shown that pharmacogenetic - based dosing of warfarin was associated in maintaining the pt - inr levels within the acceptable range for a longer time than by the standard dosing .\nunited states food and drug administration ( fda ) has recently modified the warfarin labeling by suggesting cyp2c9 and vkorc1 genotyping before initiating the drug to ensure warfarin safety .\nour patient had a fatal subdural hematoma despite low - dose ( 2.5 mg hs ) of warfarin .\nhe had massively deranged inr of 9 , was brought in with glasgow coma scale of 3 .\nthe * 1/*3 variant cyp2c9 explained this serious adverse event with low - dose warfarin . the * 3 variant is less than 5% as active as the wild type whereas * 2 retains around 12% of the activity .\na recent indian review of oral anticoagulant use revealed lack of proper laboratory facilities , with irregular pt - inr monitoring in 25% patients and deranged inr values in a high proportion of patients .\npharmacogenetic testing needs to be done only once and hence can be considered cost - effective .\nstudies have shown that along with age , gender , body weight , cyp2c9 and vkorc1 polymorphisms account for almost 64% of the variability in the dose of warfarin required for an individual .\nhence , by doing these genetic testing a priori to the treatment initiation , there is a high possibility that the patients may receive an appropriate dose than just by routine practice .\neven , several international algorithms for predicting dose of warfarin have been developed with these predicting factors of which , gage 's and wadelius algorithms have been shown to be the most accurate .\nrecently , an algorithm for indian patients has also been developed , which was found to be more accurate , sensitive and significantly reduced the risk of overestimation of dose of warfarin .\nthis algorithm can be used for predicting the appropriate dose of warfarin in our population with the genotype details of cyp2c9 and vkorc1 . to conclude\n, this case highlights the necessity of adopting the practice of routine genetic testing for cyp2c9 and vkorc1 while initiating warfarin therapy .", "answer": "warfarin is the most common and cheap oral anticoagulant currently used in clinical practice . \n a high inter - individual variation is seen in the response to warfarin . \n recently , pharmacogenetics has gained importance in managing patients on warfarin , both in predicting the optimum required dose as well as in decreasing the risk of bleeding . \n this case report is a description of a 49-year - old patient who had a lethal subdural hematoma with low - dose warfarin . \n he was subsequently found to have cyp2c9 gene polymorphism ( * 1/*3 ) . \n this case report stresses the importance of pre - prescription assessment of genetic analysis for those initiated on warfarin .", "id": 198} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nEfficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives\n\nPaper sections:\nIntroduction\nCyclic \u03b2-amino acids have for the past few decades aroused widespread synthetic interest owing to their diverse biological activities, especially applications in the field of medicinal chemistry. \u03b2-Amino acids (i.e., amino acids containing an extra methylene group in the backbone) occur naturally in peptidic structures [1][2][3][4][5] and have been used in peptide design to obtain mixed peptides that retain their biological activities [6,7].
Moreover, they can be used as starting substances for different heterocycles, as precursors for the synthesis of polymers, as potential pharmacons, for the synthesis of natural products or analogues, and also as building blocks in drug research [8][9][10][11]. Furthermore, some \u03b2-amino acid derivatives have antibiotic (oryzoxymycin) and antifungal activities (Figure 1) [12,13]. Among the cyclic \u03b2-amino acids, the most widely investigated derivatives are the five-and six-membered derivatives [8][9][10]14,15], but only a few synthetic methods are available for the synthesis of \u03b2-amino acids containing seven- [14][15][16], and eight- [14,17,18] membered rings. Only one of these studies previously reported by F\u00fcl\u00f6p and co-workers was on the synthesis of hydroxylated cyclooctane amino acids starting from 1,5-cyclooctadiene [17], the others were on the synthesis of non-hydroxylated cyclooctane amino acids [14,18]. Also in other ring systems, only non-hydroxylated cyclic amino acids and derivatives were synthesized [8][9][10]15,16]. Therefore, we were inspired to develop new methods for the synthesis of hydroxylated \u03b2-amino acid derivatives containing eight-membered rings. We have recently reported the synthesis of various eight-membered aminocyclitols and their derivatives [19][20][21][22][23][24][25]. In the present paper, we describe the synthesis of some hydroxyl-ated \u03b2-amino acid derivatives containing eight-membered rings starting from cis,cis-1,3-cyclooctadiene.
\n\nResults and Discussion\nInitially, we focused on the synthesis of \u03b2-lactam 2, which was prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, as described in the literature [26]. \u03b2-Lactam 2 was transformed into cis-amino ester 3 by cleavage of the lactam ring with HCl(g) in MeOH (Scheme 1).
N-Boc protection of cis-amino ester 3 with (Boc) 2 O in pyridine and 4-(dimethylamino)pyridine (DMAP) gave N-Boc-amino ester 4 (yield 95%). The 1 H and 13 C NMR spectroscopic data of 4 were in agreement with the proposed structure. Treatment of 4 with OsO 4 /NMO gave the expected diol 5 as a single isomer in 91% yield. We assume that the trans selectivity of hydroxyl- ation in ester 4 is due to the steric effect of the presence of the bulky Boc group. The structure of 5 was determined with the help of 1D ( 1 H and 13 C) and 2D (COSY and HMQC) NMR spectra. The diagonal peak at 4.10 ppm has cross peaks with the protons resonating at 2.96, 3.95, and 5.39 ppm, respectively, in the COSY spectrum. The cross peak between H-2 and H-3/H-4 suggests that the proton H-2 should have a trans configuration relative to the proton H-3. Removal of the Boc protection by HCl resulted in the formation of the target \u03b2-amino acid 6, which was characterized based on its NMR spectra (Scheme 1).
The N-Boc-amino ester 4 was reacted with m-CPBA to give epoxide 7 as the sole product in 94% yield (Scheme 2). The structure of 7 was assigned based on its NMR spectra. Epoxide 7 was used as the precursor material in the synthesis of the other isomer of \u03b2-amino acid 6. The ring-opening reaction of 7 with HCl(g) in MeOH resulted in a mixture of products 8 and 9 in a 9:1 ratio ( 1 H NMR). The product 8 in the reaction mixture was purified by recrystallization from ethanol/ether, but all attempts to purify the expected product 9 failed. The product 8 was obtained as the major product in 80% yield, and the expected product 9 was formed as the minor product in 4% yield. We propose that diol isomer mixture 9 can be formed by solvolysis. The presence of the lactone ring in 8 was determined by 2D NMR spectroscopic data (COSY and HMQC). The diagonal peak at 4.62 ppm has cross peaks with the protons resonating at 4.26 and 4.39 ppm, respectively, in the COSY spectra of 8. The cross peak between H-7 and H-6 showed strong correlation, which clearly supports the trans relation of the proton H-6. The cross peak between H-7 and H-10 also showed weak correlation, which clearly supports the cis relation of the proton H-10. In this reaction, lactonization and hydrolysis of the Boc group to the corresponding amine were observed. The formation of lactone 8 as the major product can be explained by nucleophilic attack of the neighbouring carboxyl group, which was formed by hydrolysis of the corresponding methyl ester.
For the synthesis of other isomeric \u03b2-amino acid derivatives, epoxide 7 was treated with two equivalent amounts of NaHSO 4 [27] in methylene chloride/MeOH at room temperature (Scheme 3). The formation of a mixture of products 10 and 11 in a 7:3 ratio was determined by NMR spectroscopy. The reaction mixture was purified using preparative silica gel TLC on a chromatotron with ethyl acetate/hexane (50:50) as the eluent to give carbamate 10 and diol isomer mixture 11 in 65% and 25% yields, respectively. However, all attempts to isolate isomer mixture 11 failed. Again, we suggest that diol isomer mixture clearly supports the trans relation of the proton H-7. Furthermore, its structure was unambiguously confirmed by single crystal X-ray analysis (Figure 2) [28]. The formation of lactone 10 can again be explained by participation of the neighbouring group, as discussed above. However, during the purification on silica gel of the lactone-Boc product, its transesterification also resulted in corresponding methyl carbamate 10.
We then investigated the epoxide-ring-opening reaction of 7 with sodium azide, to introduce an extra amino group in position 4 on the cyclooctane skeleton. For this, epoxide 7 was treated with NaN 3 in the presence of NH 4 Cl/DMF and this formed lactone 13 as the sole product in 80% yield (Scheme 4). The epoxide 7 was treated with NaN 3 and NH 4 Cl/DMF to obtain compound 12. From this reaction, the formation of unexpected lactone 13 was observed. The reaction was repeated again with only NH 4 Cl and DMF, and the reaction resulted in formation of compound 13. This experiment shows that NaN 3 / DMF does not to play any role in this transformation. The structure of 13 was elucidated with the help of the 2D NMR (COSY and HMQC) experiments. Finally, removal of the Boc group Scheme 5: Suggested mechanism for the reaction of epoxide 7 with NaHSO 4 .
from 13 with HCl(g)-MeOH resulted in the formation of cyclic \u03b2-amino acid derivative 8 in high yield.
Our suggested mechanism for the reaction of epoxide 7 with NaHSO 4 in a mixture of methylene chloride/MeOH proceeded as described in Scheme 5. First, the C=O group of the ester prefers to attack the protonated epoxide to give intermediate 15.
Then, water, which is available in methanol as an impurity, attacks the oxonium ion to give dealkylation product 10, which is a typical transesterification reaction.
To explain the formation of lactone 10, we performed a series of DFT computations using the Gaussian 16 software [29]. For this purpose, we performed geometry optimizations using the B3LYP functional [30][31][32][33]. Vibrational frequencies were computed to characterize each stationary structure. In all the computations, Pople's polarized triple-\u03b6 split valence basis set with diffuse functions, 6-311++G(d,p) [34][35][36], was utilized. The solvation model based on density (SMD) [37] was used to investigate the effects of methanol (\u03b5 = 32.613) and dichloromethane (\u03b5 = 8.93) on the computed Gibbs energies. For the TS between species A and B, the TSA-B notation is used throughout the article.
According to the given mechanism in Scheme 5, there are two possible paths for the attack of the carboxyl group on the epoxide ring. For the formation of the five-membered lactone 15 (path a), 14 \u2192 15, the reaction proceeds via a barrierless path and the solvent corrected reaction free energies are \u221217.5 and \u221218.1 kcal mol \u22121 with methanol and dichloromethane, respectively. For the formation of the six-membered lactone 16 (path b), 14 \u2192 16, the solvent corrected reaction free energy and barrier are \u22129.5 and 14.5 kcal mol \u22121 with methanol, respectively and \u221211.1 and 13.5 kcal mol \u22121 with dichloromethane, respectively (Figure 3). For the formation of the five-membered lactone 18 (path a), 17 \u2192 18, the reaction proceeds via a barrierless path and the solvent corrected reaction free energies are \u221217.2 and \u221218.0 kcal mol \u22121 with methanol and dichloromethane, respectively. For the formation of the six-membered lactone 19 (path b), 17 \u2192 19, the solvent corrected reaction free energy and barrier are \u22125.4 and 14.5 kcal mol \u22121 in methanol, respectively and \u22127.1 and 13.4 kcal mol \u22121 in dichloromethane, respectively (Figure 4). These results indicate that the formation of the methyl carbamate may occur before or after the attack by the carboxyl group. Overall, our computations demonstrate that the 14 \u2192 15 and 17 \u2192 18 conversions are kinetically more favourable, by about 14.0 kcal mol \u22121 , compared to the 14 \u2192 16 and 17 \u2192 19 conversions. These results rule out the formations of 16 and 19 at room temperature. Therefore, we conclude that the final product is lactone 10, and the formation of lactone 20 is not feasible under the experimental conditions. Furthermore, lactone 10 is energetically more stable, by 5.0 kcal mol \u22121 in methanol and by 3.7 kcal mol \u22121 in dichloromethane, than lactone 20. The computations were in good agreement with the experimental results (Figure 3 and Figure 4).
To explain why lactone 10 is formed, a conformational analysis for the epoxide 7 was performed. It is seen that the conformation is quite appropriate for the formation of lactone 10. The hydrogen bond between the C=O group of methoxy ester and NH group of the carbamate in 7 provides an appropriate conformation for the formation of lactone 10. Additionally, according to the conformational analysis of epoxide 7, the relative free energy of 7b is higher by 10.3 kcal mol \u22121 than that of 7a (Figure 5).
\n\nConclusion\nIn summary, we successfully synthesized hydroxylated cyclooctane \u03b2-amino acid 6 and its derivatives 8, 10, and 13 starting from \u03b2-lactam 2. The regioselective synthesis of lactone 8, which is a cyclic \u03b2-amino acid derivative, was achieved by oxirane ring opening in epoxide 7 with HCl(g)-MeOH, NaHSO 4 , or NH 4 Cl-DMF. The regioselectivity of oxirane ringopening in 7 was attributed to the conformational effects. The mechanism for the formation of compound 10 was elucidated with DFT computations. Our computations demonstrate that the formation of the five-membered lactone is kinetically more favourable, and the formation of six-membered lactone is not feasible under the experimental conditions. The conformation of epoxide 7 is quite appropriate for the formation of the five-membered lactone 10, in contrast to the formation of the sixmembered lactone 20. In addition, these novel compounds synthesized may be used as intermediates to design pharmacological tools.
", "answer": "The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6-en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density-functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate was confirmed by X-ray diffraction.", "id": 199} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nliquid - based cytology ( lbc ) as a technique was introduced and tried on pap smears .\nthereafter , this technique was performed for non - gynecological cytology , including conventional fine needle aspiration cytology ( fnac ) , guided fnac and fluid cytology .\nthe thin - prep ( tp ) smears were consistently devoid of obscuring elements and the cells were adequately preserved and evenly dispersed .\npitfalls noticed as cytomorphologic alterations in lbcs are small - sized cell clusters , with more single cells than sheets .\nthe cells are generally smaller , occasionally show spindling , chromatin detail is attenuated , nucleoli are more prominent , intranuclear inclusion is difficult to visualize , decrease of extracellular particles is seen , there is a decrease in the number of small mononuclear cells / red blood cells / myoepithelial cells and the background matrix is altered\n. the pathologist should be cautious in interpreting fine needle aspirations prepared using tp if that is the only methodology employed .\nthe advantages of lbc , independent of diagnostic accuracy and morphology , have been well described .\nalthough studies on lbc are documented for breast , non - gynecological specimen , thyroid , salivary gland and soft tissues , the authors supplemented bone lesions to all the above in their study .\nlbc in fnac smears can be performed on aspirates from different organs like salivary gland , thyroid , lymph nodes , breast , bone and soft tissue and other usual and guided fnac samples .\nprocessing of the samples is carried out using the tp kit , marketed by cytec corporation , malborough , ma , usa . in a comparison study , usually two passes are made .\nthe first pass is performed for the conventional preparation ( cp ) and the second pass is for the tp preparation .\ntp smears are superior to cp smears in fnac ; this fact can be proved by performing a wilcoxon 's signed rank test , p value < 0.001 .\ntp preparations are nowadays used in some sophisticated investigations like immunohistochemistry studies in breast lesions , non - hodgkin 's lymphoma ( nhl ) and hodgkin 's lymphoma ( hl ) in effusions , analysis of proliferating cell nuclear antigen ( pcna ) , cell blocks from scraping of cytosmears and comparison with conventional cell blocks .\nthe aim of our study was to determine the efficacy of lbc technology over conventional smear methods in fnac samples .\nthe study was performed on patients attending the cytology outpatient department ( opd ) of the hospital over a period of 2 years .\n, samples were processed using the liquiprep processing kit and a special kit marketed by cytec corporation .\nprocessing was performed manually in three steps , i.e. collection , concentration and cellular encapsulation .\nthe lp cytology processing kit contains a preservative solution and a cellular base . using the lbc processing kit ,\n, the samples were pushed into a preservative solution , approximately three - times the volume of the sample , and left as such for at least 1 h. this is followed by the next step , i.e. concentration , where the preserved sample is centrifuged at 3000 rpm for 30 min . for cystic fluids , the supernatant fluid is discarded and , after adding the cleaning solution , it is again centrifuged for 15 min to increase its concentration .\na pellet is produced , the supernatant fluid is discarded and a base solution of about 50 microl is added to the pellet to make a thin , homogenous suspension .\nthis suspension was placed on an ethanol - cleaned glass slide and two circular smears of 1 cm diameter were made .\nthe second option , which uses a cellular base solution , was used in certain cases , particularly if the sample contains necrotic substance or mucin .\nabout 4 ml of cleansing solution was used in selected cases , along with the preservative solution , and the processing was performed in a similar fashion .\ntwo passes were performed , the first pass was for cp and the second pass yielded material for the tp preparation , which was processed by the tp kit marketed by cytcec corporation .\ndifferent stains were used for staining the cp and lp smears , like he , pap and diff quick .\nthe representative cs and lb preparations were compared by a semiquantitative scoring system using several criteria [ table 1 ] .\nthe concentration method used in the procedure was useful in the diagnosis of cystic lesions like aneurysmal bone cysts , warthin 's tumor of salivary glands and metastatic carcinoma .\nstatistical analysis was performed using the wilcoxon signed rank test on the spss program ( chicago , il , usa ) .\nevery cytological diagnosis was recorded and tabulated and compiled to yield the p - value .\na total of 110 cases were studied , which were distributed among 30 cases of breast ( 10 fibroadenoma , four mastitis and 12 ductal carcinoma ) , 40 cases of lymph node ( 20 reactive hyperplasia , 12 granulomatous lymphadenitis , three lymphoma and five metastatic carcinoma ) , 10 cases of salivary gland ( two sialadenitis , five mixed tumor , one warthin 's tumor and two mucoepidermoid carcinoma ) , 18 cases of thyroid ( 10 colloid goiter , four thyroiditis and four carcinoma cases ) and 12 cases of soft tissue and bone lesions ( five benign and seven malignant ) .\ncomparison between cytological features in lbc and cs was carried out using the wilcoxon signed rank test separately for each organ in a tabular form , as shown in table 2 . in our study , in two cases of pleomorphic adenoma , one case of warthin 's tumor and two cases of colloid goiter , a support of cs was needed due to pitfalls in lbc described above .\nwilcoxon signed rank test statistics of lbc versus cp for breast cases , fibroadenoma , mastitis and ductal carcinoma were better diagnosed on lbc preparations due to clarity of the nuclear features [ figure 1 ] .\ncomparison data for lymph nodes suggested that the rs cells were more easily diagnosed on lbc smears due to monolayering .\nliquiprep cytosmear of the breast showing pleomorphic - looking ductal epithelial cells in a cluster and acinar pattern in a clear background in case of salivary gland lesions , the mixed salivary tumor was better visualized in the conventional smear because of preservation of the stromal component .\ncystic neoplasms of the salivary glands were better appreciated in lbc smears because of concentration . in sialoadenitis ,\nlbcs were not very useful in goiter and infectious lesions , but they proved very useful in neoplastic lesions [ figure 2 ] . in lytic bone lesions like aneurismal bone cyst ( abc ) , giant cell tumor ( gct ) and metastasis ,\nliquiprep cytosmear showing papillary carcinoma of the thyroid in a clear background with nuclear grooving the study conducted by mygdakos et al .\nlbc was favored over cs for evaluating gynecological specimens , which was approved by the fda in 1996 .\nthereafter , lbc has been found to be useful in non - gynecological cytologic specimens like fnac and body fluids , both small and large volume , which have drawn variable conclusions . in conventional fnac\nsmears , cells are admixed with debris , blood and exudates , which make the interpretation difficult .\nthere is suboptimal preservation of cells and cellular obscuring by unwanted material , leading to a high proportion of cases reported as inadequate or unsatisfactory for assessment . to overcome this problem , the lbc technique was introduced , which preserves cells in a liquid medium and removes all debris , blood and exudates , either by filtration or density gradient interpretation\n, there is even distribution of cell material , lack of obscuring factors , no drying artifact and monolayering . in our study , fnac was performed from various sites like breast , lymph node , salivary glands , thyroid and bone and soft tissue . in fibroadenoma breasts , although stromal fragments were lost , lbc proved to be useful in the diagnosis based on visualization of ductal aggregates and bipolar cells . for duct carcinomas ,\nthe wilcoxon signed ranked test for thyroid lesions [ table 2 ] , lbc was not useful in goiter and infectious lesions .\nlbc was not useful in cystic neoplasms like warthin 's tumor , mucoepidermoid and adenoid cystic carcinoma and comparable to the study by parfitt et al . for bone and soft tissues , good results were obtained in lbc because of background clearing and concentration phenomenon . in all lesions of the lymph node ,\nlbc proved to be a better option . because of the pitfalls of lbc , as described above , in some selected cases of granulomatous lymphadenitis ( lacking epitheloid cells ) , mucinous tumors ( lack of mucin ) , colloid goiter ( thin colloid fragmented ) and pleomorphic adenomas of the salivary gland ( myxoid background poor and present in droplets ) , a support on cs may prove useful .\nas observed by the authors , lbc of bony lesions do not require support of cs .\ntp preparations are superior to cps with regard to clear background , monolayer cell preparation and cell preservation .\nit is easier and less time consuming to screen and interpret tp preparations because the cells are limited to smaller areas on clear backgrounds , with excellent cellular preservation .\nhowever , tp preparations are more expensive than cp and require some experience for interpretation .\nlbc is strongly advocated in the best interest of public health , by improving the quality of the sample and reducing the likelihood of false - negative cytology results .", "answer": "background : liquid - based cytology ( lbc ) is fast becoming a useful method in evaluating both gynecological and non - gynecological preparations , including fine needle aspiration ( fna ) cytology \n . even distribution of cells , decreasing obscuring background elements like blood and mucus , well preserved nuclear and cytoplasmic details and rapid fixation helps in better visualization of cells.aim:this study was conducted to asses the diagnostic accuracy of liquid based cytology versus conventional smears in fine needle aspiration samples.study design : in this prospective study , we had 110 cases , including 30 cases of breast , 40 of lymph node , 10 of salivary glands , 18 of thyroid and 12 of bone and soft tissue . in each case , two passes were performed . \n the first pass was for conventional preparation ( cp ) and the second pass yielded material for thin - prep ( tp ) preparation . \n both cp and tp smears were compared for cellularity , background blood and necrotic cell debris , cell architecture , informative background , presence of a monolayer of cells and nuclear and cytoplasmic details by a semiquantitative scoring system . \n wilcoxon 's signed rank test on an spss program was used for statistical analysis.results:diagnostic accuracy was better in lbc smears compared with cp smears due to lack of background debris and better cell morphology , which was performed according to wilcoxon 's signed rank test , yielding a p - value of < 0.001 . \n however , in some cases , because of a decrease in cell size , clustering and altered background in lbc , a support of cp was essential.conclusion:lbc performed on fna samples can be a simple and valuable technique . only in few selected cases , where background factor is an essential diagnostic clue , a combination of both cp and tp is necessary .", "id": 200} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe epidemic of human immunodeficiency virus / acquired immunodeficiency syndrome ( hiv / aids ) is in its third decade and has reached to alarming proportions worldwide . according to the centers for disease control and prevention , more than one million people are living with hiv with an estimated 56,300 infections happening each year in the united states .\nmen who have sex with men ( msm ) population account for more than half ( 53% ) of all the new hiv infections , and blacks represent almost half ( 46% ) of people living with hiv in the united states.1 most of the hiv - related research is targeted towards high - risk groups such as prostitutes , gays and substance abusers but there is evidence that it is increasing in college students and adolescents as well.23 in 33 states with confidential name - based hiv reporting , of the 17,824 persons 13 - 24 years of age , 62% were males and 38% were females.2 an early step in preventive hiv counseling is behavioral risk assessment especially among high risk individuals in resource - limited settings.4 psychosocial stabilization as a means of coping among hiv infected individuals can not be overemphasized .\nbesides the trained hiv counselors , family physicians , who are trained in psychosocial and community medicine , are equally poised to meet this demand.5 patient - provider relationships , when it comes to hiv positive patients , are ironically constrained as risk - reduction counseling falls woefully short of required percentage.6 si - milarly , counseling for hiv positive individuals who are on treatment for maintaining treatment adherence is quite poor.7 some of the barriers may be providercentric , such as dealing with emotional issues surrounding hiv and doubtfulness of providing good care.8 these barriers faced by counselors need to be addressed by techniques such as interactive counseling , motivational interviewing and application of stages of change.9 the usa preventive services task force made a recommendation few years back of counseling all adolescents and adults about risk reduction after they have been advised about risk factors for hiv infection and sexually transmitted diseases,10 and sexual history taking.11 some of the risk factors for engaging in unsafe sexual activities among the college students are use of alcohol,12 partner characteristics such as age,13 and substance abuse.14 the determinants of safer sex in adult population vary from whether they are hiv positive males , hiv positive females , gay or a bisexual population .\nthe risk factors in a study which looked at hiv positive gays and bisexuals were mainly unprotected anal sex , which has a higher risk of hiv transmission . some of the strategies tried in this population were problem solving exercises that attempt to increase perceived benefits of safer sex .\ncounselors also made the participants aware of alternative to regular use of male condoms.15 the reason for engaging in unsafe sexual practices especially in this gay population was pleasure seeking .\nsome of the barriers for attaining safer sex are inaccurate risk perception , and gender inequalities , like women being powerless to negotiate their sexual safety.16 risk perception can be improved by using social interactions .\nsocial network formation which includes spousal communication related to aids risk has been proven to improve diffusion of behavioral change through the society.17 protection from getting hiv / aids consists of abstinence , consistent and correct condom usage and having just one sexual partner ( monogamy ) .\nseveral studies have found that pregnancy prevention rather than disease prevention was the impetus for condom use.1819 health education in the form of information about pregnancy prevention can unintentionally increase condom use .\nit was found that nigerian undergraduates , who had very good knowledge about hiv / aids , had low condom use to prevent its transmission.19 further evidence of knowledge - behavior gap comes from a study , which used a random sample survey of students in which the level of student knowledge was very high but did not lead to protective condom behaviors .\nhowever , knowledge was found to be an enabling factor in maintaining a comfort level when asking partners about their sexual histories and in requesting their partners to take an aids test.20 in a pilot project , which looked at the effect of hiv / aids prevention related messages in improving protective behaviors among indonesian participants , it was found that those exposed to the intervention were significantly more likely to use condoms to avoid aids .\nthey also felt that these messages had a great impact on them to a point of wanting to change their lifestyle.21 this study did not show conclusively that there was actual behavior change on part of the participants .\nthis helps to conclude that hiv / aids education related programs are not enough for generating a behavior change and can help in awareness of the disease to certain extent .\nfurthermore , from the point of view of clarifying risk perception , one needs to provide counseling which includes risk reduction or harm reduction as its integral part .\nthe purpose of this review is to address a number of counseling strategies used for education and counseling of individuals at risk of getting hiv / aids .\nmoreover , later in this paper are discussed some of the counseling strategies used in individuals already diagnosed with hiv or aids and these strategies were used in preventing further transmission of the disease .\nin order to collect materials for this review , a detailed search of cinahl , medline , eric , academic search premier , scopus , web of science , and social sciences citation index databases was carried out for the time period 1995 - 2010 . a boolean search strategy where the key words entered for search were counseling and strategies and hiv / aids and hiv/ aids and counseling in differing orders was used to extract studies related to counseling skills and strategies for risk reduction as well as strategies in hiv positive people .\nhiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .\nit consists of dealing with a variety of issues such as medical , psychological and social .\nclient - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word \nclient - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,\nthe risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .\nresults showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27 counseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .\nmotivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique\n, the health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .\na meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31\nhiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .\nit consists of dealing with a variety of issues such as medical , psychological and social .\nclient - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word \nclient - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,\nthe risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .\nresults showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27 counseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .\nmotivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique ,\nthe health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .\na meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31\nhiv prevention counseling is a very important mode of behavioral intervention especially in the absence of an effective vaccine or a curative treatment .\nit consists of dealing with a variety of issues such as medical , psychological and social .\nclient - centered counseling changed the focus of counseling from a sole educative one to one focusing on client 's needs and circumstances . the word \nclient - centered meant that counseling should be tailored to needs , circumstances and behaviors of a specific client which entailed active listening , to provide assistance and determining client 's specific prevention needs.22 prevention counseling primarily consists of risk reduction counseling , pretestcounseling and post - test counseling . in terms of adolescent counseling ,\nthe risk reduction approach to hiv counseling can be divided into various phases such as , exploring clients feelings about sexual activity , using their existing hiv knowledge as an engaging tool , addressing the barriers they have for safer sex , focusing on perceptions that might affect risky behaviors , focus on safe sex planning and in the end , referral making.23 risk reduction counseling is used as a harm reduction technique quite effectively.24 other interesting approaches used were information - motivation - behavior change model .\nresults showed that men who received the full information motivation behavior ( imb ) model showed greater risk reduction skills and relatively lower rates of unprotected intercourse over 6 months of follow - up and had fewer sexually - transmitted infections.25 hierarchical counseling technique as opposed to single - method counseling in a group of women showed that there was a tendency for increased protective behavior among the group which received hierarchical counseling as compared to the other two groups.26 canadian counseling guidelines for counseling related to safer sex and contraception , mention using scaled questionnaire format . in this technique , the emphasis is on the clients or patients , as they are the best judge of what is important to them personally and how they would incorporate any change in their behaviors.27\ncounseling for safer sex is used in individuals who are hiv infected to prevent further transmission of the disease .\nmotivational interviewing has been used as an effective technique by some of the hiv care providers . in this counseling technique\n, the health care provider takes into account the readiness of the client to change his / her risky behavior and helps them resolve the ambivalence associated with changing the behavior.2829 one - on - one counseling was used in these studies .\na meta - analytic review of effects of counseling and testing on sexual risk behaviors concluded that serodiscordant couples reduced unprotected intercourse and increased condom usage more than hiv - negative and untested participants.30 similarly , a multi - clinic safer sex behavioral counseling intervention using loss - frame intervention by emphasis on negative consequences of safe sex reduced the number of sexual partners among hiv positive patients compared with the control arm.31\nthere are several examples of one - on - one counseling methods used for risk reduction counseling among hiv positive individuals .\nthe various dimensions touched upon were use of a negative approach,31 assessing readiness to change,32 and motivational enhancement therapy.33 hence , we see multiple approaches used by counselors in providing education and prevention counseling to at risk individuals and also individuals who have been infected with the virus .\ninternet - based counseling has gained some popularity over recent years but has to deal with issues such as lack of visual and verbal cues , confidentiality , accessibility problems by those in great need and increased client separation.34 counseling related to using spiritual coping techniques have been well established in cancer literature but has limited evidence in hiv related counseling .", "answer": "objectives : the human immunodeficiency virus / acquired immunodeficiency syndrome ( hiv / aids ) epidemic is in its third decade and has reached to alarming proportions worldwide . according to the centers for disease control and prevention , more than one million people are living with hiv with an estimated 56,300 infections happening each year in the united states . \n diagnosis of hiv / aids via early testing along with pretest and post - test counseling is important for psychosocial stabilization and destigmatization . \n risk reduction counseling as a preventive counseling method is equally important in high - risk individuals such as adolescents , substance abusers and in gay and bisexual population . \n the purpose of this review is to address a number of counseling strategies used for education and counseling of individuals at risk of getting hiv / aids and also among those who are hiv-infected.methods:in order to collect materials for this review , a detailed search of cinahl , medline , eric , academic search premier , scopus , web of science and social sciences citation index databases was carried out for the time period 1995-2010.results:some of the various dimensions of counseling are negative approach counseling , assessing readiness to change , and motivational enhancement therapy.conclusions:multiple approaches are used by counselors in providing education and prevention counseling to at risk individuals and also individuals who have been infected with the virus . \n no one method is superior to another and some gamut of techniques are practiced by hiv / aids counselors .", "id": 201} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmost cases were reported in patients with chronic liver disease and cancer , and cases of s. algae infection in end - stage renal disease ( esrd ) patients are few .\nthe problems related to clinical practice are that little is known about the etiology of s. algae infection in esrd patients and that this bacterium is often confused with shewanella putrefaciens , although these two species may have different pathogenicities in humans .\nwe herein report a case of s. algae bacteremia in a patient with esrd and review previous case reports on shewanella infection in esrd patients .\na 71-year - old man was admitted to our hospital in mid - july because of a 5-day history of nausea and abdominal pain .\nhe had been diagnosed with chronic kidney disease ( ckd ) due to chronic glomerulonephritis and had had an arteriovenous fistula in his left arm in preparation for renal replacement therapy since two month prior to the onset .\nhe had been given an erythropoiesis - stimulating agent ( esa ; darbepoetin alpha 180 g / month ) for renal anemia ; he was not on any iron supplements .\nthe laboratory data 1 month before the onset of symptoms showed hemoglobin of 6.9 g / dl , fe of 141 g / dl , transferrin saturation ( tsat ) of 76.6% , and ferritin of 704 ng / ml , findings that were indicative of dysregulated iron metabolism .\nhe had eaten sliced raw fish or sashimi of mackerel and squid three days before the manifestations of nausea and abdominal pain , for which he visited the outpatient unit , where he was diagnosed with infectious enterocolitis and was given oral fosfomycin .\nhowever , his symptoms worsened , and he was admitted to our hospital five days after the onset of symptoms .\na physical examination showed that his blood pressure was 160/70 mmhg , heart rate 83 beats / min , and body temperature 39.5. he had abdominal tenderness without rebound tenderness .\nlaboratory tests on admission showed a white blood cell count of 3,700 /l with 83% segmented neutrophils , hemoglobin of 7.6 g / dl , mean corpuscular volume ( mcv ) of 93.4 fl , mean corpuscular hemoglobin ( mch ) of 30.2 pg , mean corpuscular hemoglobin concentration ( mchc ) of 32.5 g / dl , and platelet count of 156,000 /l .\nserum chemistries showed serum sodium 134 meq / l , potassium 5.0 meq / l , chloride 91 meq / l , calcium 5.0 mg / dl , phosphorus 11.7 mg / dl , magnesium 1.6 mg / dl , uric acid 11.8 mg / dl , blood urea nitrogen 166.9 mg / dl , creatinine 23.0 mg / dl , total protein 6.8 g / dl , albumin 2.8 g / dl , aspartate aminotransferase 27 u / l , alanine transaminase 19 u / l , lactate dehydrogenase 882 u / l , alkaline phosphatase 210 u / l , -glutamyl transpeptidase 19 u / l , creatine kinase 1,809 u / l , and c - reactive protein 11.7 mg / dl . abdominal computed tomography ( ct ) revealed intestinal swelling and fluid collection , compatible with infectious enterocolitis ( figure ) . a , b : abdominal computed tomography on admission revealed intestinal swelling and fluid collection , compatible with infectious enterocolitis .\ntwo sets of blood cultures were collected before cefmetazole ( 1 g / day ) was started . on the second hospital day , he went into cardiac arrest ; cardiopulmonary resuscitation resulted in the return of spontaneous circulation .\nantimicrobial therapy was changed to meropenem ( 2 g / day ) . on the third hospital day ,\ngram - negative bacteria appeared in both sets of the blood culture obtained on admission and were identified as s. putrefaciens 4 days later .\nceftazidime ( 2 g / day ) was given based on the susceptibility test ( table 1 ) .\nmic : minimum inhibitory concentration his condition improved ; therefore , continuous hemodiafiltration was switched to hemodialysis 3 times per week .\non the 13th hospital day , the antimicrobial agent was changed to levofloxacin and continued for 1 week .\nhe was discharged on the 26th hospital day without any complications and continued maintenance hemodialysis .\nthe bacterium recovered from the blood culture was further analyzed because the patient 's condition had deteriorated . a 16s rrna gene sequence analysis revealed that the bacterium was s. algae\ns. algae is a rare causative pathogen of bacteremia , skin and soft tissue infection , or hepatobiliary infection .\nwe reported a case of s. algae bacteremia in an esrd patient and demonstrated the probable link between raw seafood consumption and shewanella infection .\nthis patient had iron overload that was related to a dysregulated iron metabolism caused by esrd .\nraw seafood consumption by an esrd patient may be a risk factor for shewanella infection .\nshewanella species are gram - negative bacteria that are mainly isolated from the marine environment .\nthis species was once named pseudomonas putrefaciens ; it was originally classified in the family vibrioneceae until the 1990s , when it was reclassified as genus shewanella ( 1 ) .\nmost case reports of shewanella infection have described an association with exposure to seawater ; such contact can cause ear infection , skin or soft tissue infection , and bacteremia ( 1 - 3 ) .\ntwo species , s. putrefaciens and s. algae , have been reported to be pathogenic in humans ( 1 ) .\nit is often difficult to distinguish between these two species , because automated identification systems only include the database of s. putrefaciens , but not s. algae ( 2 ) .\ntherefore , some authors have suggested that the previously reported s. putrefaciens infections may have actually been caused by s. algae , which is thought to be more virulent ( 3 ) . the accurate distinction between these two species requires a 16s rrna gene sequence analysis or phenotypic tests ;\ns. algae can only grow at 42 and in 6% nacl ( 1 ) . in the present case , an automated identification system ( microscan walkaway 96 plus , siemens healthcare diagnostics , tokyo , japan ) initially determined the bacterium to be s. putrefaciens ; however , a 16s rrna gene sequence analysis confirmed the bacterium to be s. algae .\nshewanella infection can be fulminant and fatal and is often misdiagnosed as vibrio vulnificus infection , because of the similarities in their clinical manifestations ( 2,4 ) .\npatients with underlying diseases , such as hepatobiliary disease or malignancy , were reported to be predisposed to shewanella infection , as well as to v. vulnificus infection ( 3 ) ; the mortality rate of shewanella bacteremia was increased in these patients ( 5 ) .\nshewanella species belong to the microflora of the marine environment , and exposure to seawater was reported to be one of the risk factors for shewanella infection , especially in temperature regions ( 3 ) .\ntherefore , more attention should be paid to the pathogenicity of this bacterium , especially in patients with underlying diseases who are exposed to these environments .\nthere have been seven previously published case reports on shewanella infection in esrd patients ( 4,6 - 11 ) ( table 2 ) .\ntwo cases were reported to be caused by s. algae and four cases by s. putrefaciens ; however , only two cases were further analyzed by a biochemical procedure .\nthe most common route of infection was skin ulcer ( 3 cases ) , followed by catheter - related infection ( 2 cases ) ; no case was related to oral intake of seafood . in the present case ,\nthe onset of symptoms was related to seafood consumption , and abdominal ct scan showed signs of infectious enterocolitis .\ntherefore , we concluded that the shewanella infection in this patient was probably caused by dietary intake of raw fish or sashimi .\nthis was the first case of s. algae infection that might have been transmitted orally in an esrd patient .\nesrd : end - stage renal disease , flux : flucloxacillin , gm : gentamicin , pipc : piperacillin , cpfx : ciprofloxacin , cez : cefazolin , lvfx : levofloxacin , mino : minocycline , cfpm : cefepime , caz : ceftazidime , mepm : meropenem , vcm : vancomycin , doxy : doxycycline , drpm : doripenem , amk : amikacin although the reason why the esrd patient was predisposed to shewanella infection is still unclear , dysregulated iron metabolism may be a risk factor for this patient .\niron is not freely available , since it binds to transferrin in the blood ( 12 ) .\npseudomonas and vibrio species have the ability to produce siderophore , which plays an important role in supplying iron to bacteria ( 12,13 ) .\nsiderophore has a high affinity to iron and is able to displace iron from transferrin .\ns. algae was reported to produce siderophore and was capable of absorbing iron into its body ( 14 ) .\npatients with hepatobiliary diseases who are susceptible to s. algae often had the complication of iron overload .\nthe association between shewanella infection and hepatobiliary diseases may be due to iron overload ( 5 ) . in the present case\n, the patient did not have hepatic dysfunction but did have esrd with a dysregulated iron metabolism ; his anemia was esa - resistant , and there seemed to be excessive iron levels , although he was not taking any iron supplement .\nit was suspected that uremia of the patient contributed to the esa - resistant anemia , because the patient was just starting renal replacement therapy , and the serum creatinine level on admission was extremely high .\nrecent studies have demonstrated that hepcidin , which reduces iron release from reticuloendothelial and hepatocyte stores , plays an important role in the disordered iron metabolism of uremia including esa resistance ( 15,16 ) .\nthe serum hepcidin level is related to the residual renal function and elevates in ckd and in esrd patients ( 15,17 ) .\nserum hepcidin can be removed by renal replacement therapy ( 18 ) , and insufficient hemodialysis is known to cause esa - resistant anemia ( 19 ) . therefore\n, we speculated that the esrd , especially the accompanying iron overload , might have been a risk factor for shewanella infection in this patient . to our knowledge ,\nno previous report has described the status of iron metabolism in the esrd patients with shewanella infection .\nthe limitation of this report was that the data for serum ferritin and tsat on admission were not available .\nhowever , we measured both of these markers at one month before the onset , when the patient was in a stable condition without acute inflammation or infection .\niron status should be evaluated based on ferritin and tsat in ckd and esrd patients ( 19,20 ) .\nthe ferritin level and tsat of the patient in the present study were compatible with iron overload ( 21,22 ) .\nin addition , we were unable to recover s. algae from a stool culture on the eighth hospital day , when the patient had already received courses of an antimicrobial agent to which the bacterium was susceptible .\nwe could not collect a stool sample at an earlier time , such as at admission , because of the patient 's critically ill condition . in conclusion , we reported a case of s. algae bacteremia that was probably caused by oral intake of raw fish in an esrd patient .\nin addition , a dysregulated iron metabolism in esrd may be a risk factor for shewanella infection .", "answer": "a 71-year - old man was admitted because of nausea and abdominal pain . \n he was receiving an erythropoiesis - stimulating agent for anemia and dysregulated iron metabolism due to stage g5 chronic kidney disease . \n he had a history of raw fish intake and was diagnosed with infectious enterocolitis , which worsened and led to septic shock . \n shewanella putrefaciens grew in the blood culture , but shewanella algae was identified in a 16s rrna gene sequence analysis . \n we herein report a case of s. algae bacteremia believed to have been transmitted orally . \n we also reviewed previous case reports on shewanella infection in end - stage renal disease patients .", "id": 202} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\neligible subjects were healthy individuals who voluntarily received routine comprehensive health check - ups , including computed tomography ( ct ) scan analyses of abdominal adipose tissue , from january to december 2008 at the seoul national university hospital healthcare system gangnam center .\ndata were collected through a questionnaire , anthropometric measurements , blood samples , and ct scans .\ndetailed descriptions of the method used for the measurement of abdominal adipose tissue have been published previously ( 8) . in brief , a 5-mm thick umbilical level abdominal section from 16-detector row ct imaging of the abdomen was obtained .\nthe cross - sectional area ( cm ) of the abdominal fat was calculated using rapidia 2.8 ct software ( infinitt , seoul , korea ) .\nthe vat area was defined as intra - abdominal fat bound by parietal peritoneum or transversalis fascia , and the sat area was calculated by subtracting the vat area from the total adipose tissue area . because of the high colinearity between sat and vat , adjustments to the regression model or stratification of vat are insufficient to control for the effects of vat on sat .\nthe ratio between sat and vat ( sat / vat ratio [ svr ] ) was therefore calculated and used in the current study .\nmets was defined according to the modified national cholesterol education program adult treatment panel iii ( 9 ) and asia - pacific abdominal obesity criterion ( 10 ) . means with 95% ci and\nnumbers of participants ( % ) with metabolic risk factors were compared across the svr quintiles .\nwe used multivariate logistic regressions to evaluate the association between mets and svr after adjusting for age , smoking , alcohol consumption , bmi , menopausal status , and hormonal replacement therapy ( women only ) .\ndata are expressed as odds ratio ( or ) [ 95% ci ] ; and p for trend .\ndetailed descriptions of the method used for the measurement of abdominal adipose tissue have been published previously ( 8) . in brief , a 5-mm thick umbilical level abdominal section from 16-detector row ct imaging of the abdomen was obtained .\nthe cross - sectional area ( cm ) of the abdominal fat was calculated using rapidia 2.8 ct software ( infinitt , seoul , korea ) .\nthe vat area was defined as intra - abdominal fat bound by parietal peritoneum or transversalis fascia , and the sat area was calculated by subtracting the vat area from the total adipose tissue area . because of the high colinearity between sat and vat , adjustments to the regression model or stratification of vat are insufficient to control for the effects of vat on sat .\nthe ratio between sat and vat ( sat / vat ratio [ svr ] ) was therefore calculated and used in the current study .\nmets was defined according to the modified national cholesterol education program adult treatment panel iii ( 9 ) and asia - pacific abdominal obesity criterion ( 10 ) .\nmeans with 95% ci and numbers of participants ( % ) with metabolic risk factors were compared across the svr quintiles .\nwe used multivariate logistic regressions to evaluate the association between mets and svr after adjusting for age , smoking , alcohol consumption , bmi , menopausal status , and hormonal replacement therapy ( women only ) .\ndata are expressed as odds ratio ( or ) [ 95% ci ] ; and p for trend .\nforty percent of men and 25% of women had elevated blood pressure , 31% of men and 15% of women had elevated fasting glucose , and 25% of men and 14% of women had mets .\nthe mean sat and vat areas were 139.8 cm and 134.4 cm in men and 173.1 cm and 80.0 cm in women , respectively .\nthe prevalence of elevated fasting glucose , elevated triglycerides ( tgs ) , and reduced hdl cholesterol ( hdl - c ) significantly decreased as the svr quintile increased ( 26 , 16 , and 37% in quintile 1 vs. 5 , 4 , and 11% in quintile 5 , respectively ; all p for linear trend < 0.05 ) robust linear decreases in these risk factors were also seen among men ( supplementary table 1b ) .\nors of mets significantly decreased across all 5 quintiles of the svr after adjusting for covariates in both men ( or 1.0 for quintile 1 vs. 0.5 in quintile 5 ; 95% ci 0.30.7 for quintile 5 ; p for linear trend < 0.01 ) and women ( or 1.0 for quintile 1 vs. 0.2 in quintile 5 ; 95% ci 0.10.5 for quintile 5 ; p for linear trend < 0.01 ) ( table 1 ) .\nunadjusted and adjusted ors and 95% ci from logistic regressions predicting the likelihood of mets for each of the svr quintiles * adjusted ors take into consideration age , smoking , alcohol consumption , bmi , and menopausal status , hormone replacement therapy ( women only ) .\nors of mets significantly decreased across all 5 quintiles of the svr after adjusting for covariates in both men ( or 1.0 for quintile 1 vs. 0.5 in quintile 5 ; 95% ci 0.30.7 for quintile 5 ; p for linear trend < 0.01 ) and women ( or 1.0 for quintile 1 vs. 0.2 in quintile 5 ; 95% ci 0.10.5 for quintile 5 ; p for linear trend < 0.01 ) ( table 1 ) .\nunadjusted and adjusted ors and 95% ci from logistic regressions predicting the likelihood of mets for each of the svr quintiles * adjusted ors take into consideration age , smoking , alcohol consumption , bmi , and menopausal status , hormone replacement therapy ( women only ) .\nthe purpose of this study was to assess the cross - sectional correlation of abdominal sat with mets in a korean study population .\nwe found that as the svr increased , mets components such as reduced hdl - c , elevated tgs , and elevated fasting glucose decreased in both sexes . furthermore , this relationship was maintained even after the adjustment for a variety of variables .\nsmall adipocytes in sat play the role of powerful buffers , uptaking circulating free fatty acids and tgs in the postprandial period .\nbut if they lose their function in adipogenesis or fat storage capacity in sat , fat begins to accumulate in tissues not suited for lipid storage such as vat .\nperoxisome proliferatoractivated receptor- ( ppar- ) agonists stimulate the differentiation of adipocytes , resulting in increased accumulation capacity in sat ( 12 ) .\nthe ppar- coactivator 1 mrna expression is significantly higher in subcutaneous fat than in omental fat ( 13).this mechanism explained the finding that treatment with thiazolidinedione improves insulin sensitivity ( 6 ) . vat and sat differ in cytokine secretion profile such as leptin , adiponectin , interleukin-6 , interleukin-8 , plasminogen activator inhibitor 1 , and angiotensin , which may play some role in the development of mets ( 14,15 ) .\nlongitudinal associations of vat / sat change with mets , and with leptin and/or adiponectin level should be the focus of future studies .\ngluteofemoral sat , which may act as a confounding factor , was not considered in the study .\nhowever , the current study included the analysis of a large dataset of ct - measured sat and vat .\nmoreover , the study population was generally healthy , which implies that the results can be applied to the general korean population .", "answer": "objectivethis study aimed to assess the correlation between abdominal subcutaneous adipose tissue ( sat ) and metabolic syndrome ( mets ) in korean adults after adjusting for the effects of visceral adipose tissue ( vat).research design and methodsthe sat / vat ratio ( svr ) was calculated using abdominal computed tomography in 2,655 subjects . \n we used regression analyses to assess whether the svr predicted mets.resultsfor both sexes , the prevalence of elevated triglycerides , reduced hdl , and elevated fasting glucose significantly decreased with increasing quintiles of svr ( p for trend < 0.05 ) . the prevalence and odds ratios of mets significantly decreased as the svr increased ( men : odds ratio 0.5 [ 95% ci 0.30.7 ] ; women : 0.2 [ 0.10.5 ] for comparisons of lowest vs. highest quintile ; p for trend < 0.05).conclusionsafter adjustment for vat , abdominal sat was inversely correlated with the occurrence of mets .", "id": 203} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a recent issue of critical care , meyer and colleagues report interesting surveillance data from icus in 30 german hospitals , based on a large amount of microbiology and pharmacy data gathered between 2001 and 2008 .\none of the main study findings is a decreasing rate of methicillin - resistant staphylococcus aureus ( mrsa ) and a dramatic increase of third generation cephalosporin ( 3gc ) resistant enterobacteriaceae over the study period . in recent years\n, most european countries have succeeded in reducing the burden of disease caused by mrsa .\nthis progress has , however , been partly off set by the increase across europe in the prevalence of multiresistant gram - negative pathogens producing extended - spectrum betalactamases ( esbls ) or carbapenemases .\nthe current study confirms this worrisome finding and also shows an increase in carbapenem , 3gc and fluoroquinolone use in german icus with a stable volume of overall antibiotic use .\nthe latter two antibiotic classes have been repeatedly identified as risk factors for carriage of multidrug resistant gram - negatives .\ncarbapenems on the other hand are first - line drugs for the treatment of infections due to esbl - producing bacteria .\nit is tempting to assume that overuse of fluoroquinolones and 3gc antibiotics contributed to the observed increase in esbl producers , which subsequently increased carbapenem use .\nthe ecological nature of the data , however , makes it difficult to infer clear cause - and - effect relationships , as does the failure to differentiate between hospital- and community - acquired isolates and clinical versus surveillance cultures .\nin addition , the analysis of trends is hampered by variation in the number of participating icus over time .\nnevertheless , the increased burden of multidrug - resistant gram - negative bacteria is a real phenomenon .\nin contrast to mrsa , esbl producers - notably strains of escherichia coli carrying plasmids of the ctx - m family - are mostly imported from the community into the hospital . assuming a relationship with antibiotic use in animals and subsequent transmission of antibiotic resistant e. coli via the food chain is alluring , but strong epidemiological evidence is still lacking .\nthe recently started european union - funded saturn project ( impact of specific antibiotic therapies on the prevalence of human host resistant bacteria ) will gather more information on these risk factors . as mentioned above\n, antibiotic overuse in humans probably plays a central role in the spread of esbl producers . in the context of this study\nit is noteworthy that germany has a relatively high level of fluoroquinolone use in the community . as to antibiotic use in hospitals ,\nthe overall quantity of antibiotic use in german icus is comparable to that of other countries .\nalthough there is important heterogeneity between icus , inappropriate antibiotic use is still common in germany ( as in many other countries ) , where infectious diseases as a stand - alone speciality and antibiotic stewardship programmes are still underdeveloped . compared to other european countries or highly publicised health threats , such as bioterrorism and swine flu , public awareness and political commitment to control multidrug - resistant microorganisms has been slow to rise in germany . only recently ( 2009 )\nhas a german reference centre for surveillance of gram - negative bacteria been established , which focuses , among other things , on detection of carbapenemase producing bacteria .\na first outbreak of carbapenemase producing klebsiella pneumoniae in germany has recently been reported , probably linked to an index patient with previous healthcare contact in greece .\nthe fact that two icus in 2008 reported carbapenem resistant k. pneumoniae in the current study raises the concern that these strains might already be more common in central europe than previously assumed since detection of these strains may be difficult with routine laboratory techniques .\nwith regard to esbl - producers the growing community reservoir makes it unlikely that we will be able to control the spread by conventional measures targeted at nosocomial infection control .\nthe promotion of prudent antibiotic use in the community and animal husbandry should therefore be a key priority .\nas to carbapenemase - producing enterobacteriaceae , early identification of these strains and aggressive infection control measures seem essential .\nexamin ing novel decolonization strategies for gram - negative enterobacteriacae might be a further strategy worth evaluating .\nif we manage to enforce all these measures , we will hopefully be able to think positive again - even with regard to gram - negatives .\n3gc : third generation cephalosporin ; esbl : extended - spectrum betalactamase ; mrsa : methicillin - resistant staphylococcus aureus .\npreparation of this commentary was supported in part by the 6th and 7th framework programme of the european community in the context of the projects ' changing behaviour of health care professionals and the general public towards a more prudent use of anti - microbial agents ' ( champ , contract sp5a - ct-2007 - 044317 ) and ' impact of specific antibiotic therapies on the prevalence of human host resistant bacteria ' ( acronym saturn , agreement fp7-health-2009-n241796 ) .", "answer": "the increasing prevalence of multiresistant gram - negative bacteria of the enterobacteriaceae family in europe is a worrisome phenomenon . \n extended spectrum betalactamase - producing escherichia coli strains are widespread in the community and are frequently imported into the hospital . \n of even more concern is the spread of carbapenem - resistant strains of klebsiella spp . from regions where they are already endemic . \n antibiotic use is a main driver of antibiotic resistance , which again increases broad spectrum antibiotic use , resulting in a vicious circle that is difficult to interrupt . \n the present commentary highlights important findings of a surveillance study of antimicrobial use and resistance in german icus over 8 years with a focus on gram - negative resistance .", "id": 204} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nEnantioselective Synthesis of \\xce\\xb1-Secondary and \\xce\\xb1-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation\n\nPaper sections:\n\nPiperazine is a common structural motif in pharmaceuticals and is considered to be a privileged scaffold in medicinal chemistry.[1] Piperazine itself has been used as an anthelmintic and notable piperazine-containing small molecule pharmaceuticals include imatinib (1), a kinase-inhibiting anticancer agent;[2] ciprofloxacin (2), a potent fluoroquinolone antibiotic;[3] piribedil (3), an antiparkinsonian agent;[4] and indinavir (4), an HIV protease inhibitor (Figure 1a).[5] Common methods for the selective asymmetric preparation of substituted piperazines[6] include enantio selective hydrogenation,[7] enzyme-mediated chiral resolution,[8] \u03b1-lithiation mediated by (\u2212)-sparteine and other chiral diamines,[9] Pd-catalyzed cyclizations,[10] or synthesis from amino acids or other members of the chiral pool.[11] One of the most straight forward methods for the synthesis of chiral piperazines is the reduction of the corresponding chiral keto- or diketopiperazine. However, methods for the asymmetric preparation of these piperazine precursors are currently limited.
Piperazin-2-ones possess an additional functionality (i.e. the carbonyl) that allow for the synthesis of more highly substituted piperazine-2-ones, which, upon reduction, yield substituted piperazine derivatives. Although piperazin-2-ones are employed infrequently in medicinal chemistry, they can be found in some pharmaceutical agents including the p53/MDM2 inhibitor (\u2212)-nutlin-3 (5, Figure 1a),[12] and in several naturally occurring bioactive compounds including the marcfortines,[13] pseudotheonamides,[14] and malbrancheamides (Figure 1b).[15] Piperazin-2-ones also play a crucial role as conformationally constrained peptidomimetics. These piperazin-2-ones mimic inverse \u03b3-turns in peptides, which play crucial roles in the secondary structures of proteins.[16] Chiral piperazin-2-ones[17] can be prepared from amino acids or other members of the chiral pool[18] or by chiral auxiliary-mediated alkylations[19] or dynamic resolutions.[20] However, most of the available methods are not capable of generating chiral \u03b1-tertiary piperazin-2-ones (6, Figure 2) and there are no previous examples that prepare this motif by catalytic enantioselective methods. Thus, there is an unaddressed absence of catalytic asymmetric synthesis strategies to these valuable compounds.
Our research group has had a longstanding interest in the construction of \u03b1-tetrasubstituted carbonyl compounds including quaternary centers using transition metal catalysis and has developed conditions for the asymmetric allylic alkylation of lactams to furnish \u03b1-quaternary lactam products.[21] Morpholin-3-ones were also identified as viable substrates under the same conditions, generating an \u03b1-tertiary stereo center.[22] We sought to extend this catalyst system to enantio selectively generate \u03b1-tertiary piperazin-2-ones (6), which, upon subsequent reduction, would generate chiral tertiary piperazines (7). \u03b1-Tertiary piperazine species are not well precedented in the literature presumably due to the difficulties associated with their preparation, and no general methods exist for their asymmetric synthesis, let alone catalytic asymmetric synthesis. A direct, catalytic asymmetric synthesis of tertiary piperazin-2-ones and their subsequent reduction to the piperazines would provide access to an invaluable scaffold, enabling the exploration of unprecedented chemical space (Figure 3).
Medicinal chemistry has long utilized linearly substituted, non chiral piperazines and has also, although less frequently, utilized chiral \u03b1-secondary piperazines, as in indinavir (4).22 Access to enantiopure \u03b1-tertiary piperazines would provide a unique opportunity to explore these three dimensionally elaborated piperazines in drug discovery.
Given that secondary and tertiary nitrogen atoms may exhibit undesired reactivity in Pd-catalyzed reactions, it is necessary to protect both nitrogens of the ketopiperazine ring. Taking into consideration our prior results, in which N-benzoyl protected lactams reacted with high enantioselectivities in the decarboxylative asymmetric allylic alkylation,[21e] we began our studies with the 1,4-bisbenzoylated piperazin-2-one 8a (Table 1). When utilizing Pd2 (pmdba)3 [tris(4,4'-methoxydibenzylideneacetone) dipalladium (0)] at 5 mol % catalyst loading and the (S)-(CF3)3-t-BuPHOX ligand at 12.5 mol % loading in a 0.014 M solution of toluene, the bis-N-benzoylated \u03b1-allylated product 9a (Table 1) was formed in high yield but modest ee. It was reasoned that the sp2-hybridized nature of the N(4) position was detrimental to the enantioselectivity of the reaction due to its ability to stabilize the enolate intermediate.[23] Taking into consideration the need for an alkyl protecting group at the N(4) position, we next examined 4-benzylpiperazin-2-one 8b (R1=Bz, R2=Bn, R3=Me, R4=H). Under our standard conditions, the N-benzyl-protected \u03b1-allylated compound 9b was obtained in both good yield and ee. Additional N(4)-protecting groups were investigated which allow for the chemoselective deprotection of N(4). The para-methoxybenzyl protecting group, which can be cleaved by acidic or oxidative conditions, would allow for orthogonal deprotection. 4-Methoxybenzylpiperazin-2-one 9c was also obtained in good ee but with slightly lower yield than the 4-benzyl compound 9b. Given the slightly higher yield, the 4-benzyl protecting group was selected for further optimization.
In efforts to increase the ee of the allylic alkylated products, additional protecting groups at the N (1) position were examined. Considering that benzoylated compounds provided the best results in the lactam case,[21e] we examined additional acyl protecting groups (Table 1). The para-fluoro benzoyl and para-methoxybenzoyl compounds 9d and 9e were obtained in nearly identical ee and just slightly lower yields, demonstrating that substantial electronic changes of the N(1)-substituent do not have a strong influence on the reaction efficiency or selectivity. However, the reaction is somewhat sensitive toward ortho substitution at the N(1)-benzoyl group as 9f was obtained in a significantly lower enantiomeric excess compared to 9d and 9e. Additionally, the1-carboxybenzyl ketopiperazine 9g was also prepared in high yield, albeit moderate ee. Given these data, the unsubstituted benzoyl group was selected as the optimal choice of N(1)-protecting group, and the benzyl group was selected as the optimal N(4)-group.
With protecting groups for both nitrogen atoms investigated, the scope of the reaction with regard to the \u03b1-substituent was examined. Piperazin-2-ones bearing alkyl (9h, 9i) and benzyl (9j) groups were prepared, as was benzyl ether 9k (Table 1), which provides an additional handle for further functionalization. Additionally, bicyclic product 9n, which is reminiscent of the marcfortine core, was obtained in good yield in the reaction (Table 1). The effect of expanding ring size was also examined. The 1,4-diazepan-2-one 9o was formed with only moderate enantiomeric excess, a result that suggests that the reaction is sensitive to ring size, contrary to the lactam examples.[21e]
Common piperazine pharmacophores include N-arylpiperazines and N-methylpiperazines,24 and we sought to determine if 4-aryl ketopiperazines and 4-methyl ketopiperazines were also competent substrates in this chemistry. The low ee observed in bis-benzoylated compound 9a suggests that an sp2-hybridized N(4) position would prove detrimental to the enantioselectivity of the reaction. Despite this, 4-phenyl compound 9p, with its partial sp2-nature of its aniline nitrogen, could be obtained in good yield and with excellent enantiomeric excess (Table 1). The 4-methylketopiperazine 9q could also be prepared in good yield but with slightly diminished ee.
Contrary to results with the piperdinone substrates, we were delighted to find that even the unsubstituted \u03b1-secondary ketopiperazine 11a could be obtained in excellent yield and enantioselectivity (Table 2). Previous attempts to generate trisubstituted stereo centers via our asymmetric allylic alkylation of lactam and ketone substrates were unsuccessful. Such experiments have generally resulted in mixtures of mono-, di-, and unallylated products, and the desired trisubstituted product was formed in poor yield and with only moderate ee. We were delighted to find that in the case at hand, unsubstituted \u03b1-secondary ketopiperazine 11a could be obtained with no detectable amounts of di- or unallylated byproducts. It is likely that the low acidity of the \u03b1-hydrogen of the monosubstituted piperazin-2-one substrate and product is key to obtaining a high yield of the monoallylated product. Given this exciting result, additional allyl substrates were tested (Table 2). Numerous allyl groups are compatible, including methallyl 11b, chloroallyl 11c, and phenylallyl 11d which were all obtained in fair to excellent yield and high enantioselectivity.
The ketopiperazine products can be converted to the related piperazines in two steps, hydrolysis of the benzoyl group to piperazine-2-one 12 followed by reduction of the amide to piperazine 13 (Scheme 1A). The deprotected N(1) position can be further alkylated to form for instance, di-allyl piperazin-2-one 15 (Scheme 1B). Cross-metathesis can also be performed (Scheme 1C). Additionally, the 4-methoxybenzylgroupcan be selectively cleaved under oxidative conditions to form piperazine-2-one 17 (Scheme 1D).
Finally, we have demonstrated that these tertiary piperazines can successfully be incorporated into known piperazine-containing pharmaceuticals, leading to novel analogs with comparable bioactivities in preliminary testing. Substitution on the piperazine ring has been shown to modulate bioactivity and, in some cases, result in more specific and stronger enzyme binding.[25] We considered imatinib (1), an antiproliferative agent developed for the treatment of several cancers, notably including Philadelphia chromosome-positive chronic myelogenous leukemia (CML),[2] to be an ideal candidate for proof of concept. Imatinib targets the Abl tyrosine kinase domain of the Bcr-Abl fusion protein, and it is known that genetic point mutations can render imatinib ineffective because it is no longer able to bind to the enzyme.[26] The piperazine moiety of the molecule forms two key hydrogen bonds to two amino acid residues, and thus plays a crucial role in binding.[27]
Given that the piperazine is so crucial to the binding of imatinib, we wanted to explore whether highly substituted and congested piperazine analogs would disrupt these interactions. Enantiomerically pure, benzylated analog 18 (Scheme 2) was assessed for its antiproliferative activity against the human K562 CML cell line.
N-substituted analog 18 was found to have significantly less antiproliferative activity than imatinib (1, Table 3) signifying that too much bulk around N(4) might perturb key interactions. We also synthesized two novel des-methyl tertiary piperazine-containing imatinib analogs (Scheme 2). These analogs, (S)-20 and (R)-20, were assayed for their antiproliferative activity and were found to have activities slightly greater than that of N-desmethyl imatinib (CGP 74588) 19, the main bioactive metabolite of imatinib. The (R)-enantiomer is slightly more potent ((R)-20, Table 3). These results point to the potential utility of stereochemically-rich piperazines as important building blocks for medicinal chemistry. Additionally, these novel substructures will likely open up new chemical space around a privileged scaffold in drug discovery.
In summary, we have developed the first catalytic enantioselective synthesis of \u03b1-tertiary piperazin-2-ones. These important molecules can be easily converted to novel \u03b1-tertiary piperazines. This method utilizes palladium catalysts derived from Pd2(pmdba)3 and electron-deficient PHOX ligands to deliver \u03b1-tertiary piperazin-2-ones in good to excellent yields and enantioselectivities. This method also allows for the synthesis of \u03b1-secondary piperazin-2-ones in modest to excellent yields and good to excellent enantioselectivities. In addition to being tolerant of a variety of N-substitutions, this reaction is also tolerant of substitution at the stereocenter including fused bicycles such as those found in piperazine-2-one-containing natural products. We have further demonstrated that these chiral piperazin-2-ones can be reduced to the corresponding chiral piperazines, and these chiral \u03b1-tertiary piperazines can successfully be incorporated into known piperazine-containing pharmaceuticals. Specifically, these piperazines can be incorporated into the imatinib framework without major perturbation of the drug's antiproliferative activity against the human K562 CML cell line, thus indicating the enormous potential that these novel three-dimensionally elaborated chiral piperazines have in drug discovery.
", "answer": "The asymmetric Pd-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows for the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogs. The introduction of these chiral tertiary piperazines resulted in imatinib analogs that exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.", "id": 205} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nventriculo - peritoneal ( vp ) shunting is the preferred and most successful method for managing congenital hydrocephalus .\nabdominal complications include peritonitis , ascites , bowel obstruction , bowel and abdominal wall perforation , and inguinal herniae .\nan uncommon but recognized complication is formation of an abdominal pseudocyst , with cerebrospinal fluid ( csf ) collecting and being poorly absorbed or not absorbed across the serosa .\nthe continuous flow of csf within a confined space leads to increased pressure within the abdominal cavity , reducing forward pressure gradient and , eventually , shunt malfunction .\nthese pseudocysts have traditionally been treated with surgical shunt externalization , antibiotics , and a second surgical procedure for shunt reinsertion .\nexploratory laparotomy with a partial excision pseudocyst and placement of a catheter in a quadrant of abdomen is also an option .\nwe report a 20-month - old female child with a vp shunt and a gradual distension of abdomen since three months , respiratory distress , and bilious vomiting for two days .\nright - sided vp shunt insertion was done on the seventh day of life and meningomyelocele repair on the 15 day of life . at the age of three months\n, there was shunt malfunction for which the right - sided vp shunt was removed and a vp shunt was inserted on the left side . at the time of index admission\n, she presented with a history of gradual distension of abdomen for 3 months and respiratory distress and bilious vomiting for 2 days .\n, there was a large , 15 cm 12 cm , nontender , cystic intraperitoneal lump with a smooth surface and ill - defined margins , occupying almost the entire abdomen ; moreover , fingers could be insinuated between the costal margins and the lump .\nx - ray of the abdomen showed vp shunt in the left side of the abdominal cavity having ground glass opacity around the shunt , with the displacement of bowel loops to the periphery of the opacity [ figure 1 ] . abdominal ultrasonography\n( usg ) revealed a large multiseptate pseudocyst with the presence of the shunt within .\nas the baby had considerable respiratory distress , an ultrasound - guided aspiration of 200 ml of a straw - colored fluid was done .\nhowever the fluid recollected immediately with increasing abdominal distension and the symptoms persisted ; hence , we decided to operate on the child .\nx - ray abdomen showing a giant psuedocyst on the left lower abdomen with a shunt in situ we went ahead with two - port laparoscopy ; one 5-mm primary epigastric camera port above the cyst placed under vision and one 5-mm port in the right iliac fossa .\nthe placement of the second port was difficult , as there was a large csf pseudocyst predominantly on the left side of the abdomen , with multiple adhesions of bowel loops around the pseudocyst .\ngentle maneuvering and dissection with the scope itself helped identify a window in the right iliac fossa where the second port could be placed .\na grasper was used to gently free all adhesions of the cyst wall to parietes .\nthe cyst was incised with a hook cautery and 1,100 ml of the csf fluid was drained .\nthe incision in the cyst wall was extended carefully so as to avoid injury to the adherent bowel loops , and the cyst was then deroofed .\nthe shunt was repositioned in the right subdiaphragmatic space over the liver after confirming the patency of shunt with a free flow of the csf .\n. on sixmonth follow - up , the child is recovering well and is asymptomatic .\ninsertion of a vp shunt is the preferred and most successful method for the management of congenital hydrocephalus . in the setting of a vp shunt ,\nthe time from the last shunt procedure to the development of the abdominal csf pseudocyst ranges from 3 weeks to 5 years .\na chest and abdominal x - ray visualizes the position of the thoracoabdominal part of the vp shunt .\npathi reported that ultrasound and computerized tomography features of the vp shunt floating in the thickened sac wall would allow early recognition of this complication .\nthese pseudocysts have traditionally been treated with surgical shunt externalization , antibiotics , and a second surgical procedure for shunt reinsertion . moreover , exploratory laparotomy with partial excision and marsupialisation of pseudocyst and placement of catheter in a quadrant of abdomen has been done .\nan extensive review revealed increasing use of laparoscopic management of this complication . using the technique of laparoscopy , kim et al . excised a portion of the csf pseudocyst , removed the shunt catheter from the residual cavity , and repositioned it within the peritoneal cavity in a 12-year - old boy .\n( 2003 ) found that the laparoscopic management of csf pseudocyst , accomplished through 3-mm to 5-mm ports with the help of delicate laparoscopic instruments , minimizes the risk of a laparotomy , and the formation of intraperitoneal adhesions .\nfurthermore , laparoscopy allows visual confirmation of the adequate flow of the csf from the end of the catheter after it is repositioned .\nhowever , the greatest advantage of laparoscopy lies in its ability to assess the entire abdominal cavity for the presence of adhesions and undertake adhesiolysis when necessary .\nthis allows placement of the catheter in the quadrant of the abdomen with the maximum absorptive surface .\nmartin et al . performed laparoscopy in ventriculoperitoneal shunt revision for pseudocyst in two cases and reported the use of extensive adhesiolysis for decreasing the risk of future adhesive obstruction and extending shunt life and thus , recommended laparoscopy for vp shunt revisions .\nperformed the laparoscopic drainage of a pseudocyst containing 2 liters of fluid and retrieved the catheter from the peritoneal cavity .\nesposito et al . recommended that laparoscopy is a safe procedure in patients with abdominal complications of vp shunts , especially in adhesions and pseudocyst formation . on extensive search and review of literature\n, we found that minimally invasive technique is a useful modality for the treatment of this complication .\nhowever , the management of this complication is generally done using three ports ( one camera port and two working ports ) .\nwe recommend that even giant pseudocysts can be managed by the two - port laparoscopic technique as done in another child with giant csf pseudocyst as well .\nto summarize , laparoscopy is a useful modality for the treatment of intra - abdominal complications of vp shunt such as adhesions and pseudocyst .\nit is effective , avoids multiple laparotomies , and its attendant complications and future adhesions .\nit is feasible to manage this complication by using only the two - port laparoscopic technique .", "answer": "insertion of a ventriculo - peritoneal ( vp ) shunt is the most common operative procedure for the treatment of hydrocephalus in children . of the several causes of shunt malfunction , \n cerebrospinal fluid ( csf ) pseudocyst is relatively uncommon . \n there are several modalities to treat a csf pseudocyst . \n laparotomy is required , at times , more than once . \n we managed a patient of csf pseudocyst with two - port laparoscopy , by deroofing the psuedocyst and repositioning of the shunt . \n this minimally invasive technique avoids morbidity associated with laparotomy and aids in early recovery .", "id": 206} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan infliction in the life expectancy figure of patients with sickle cell disease ( scd ) occurred around the middle of the 1970s ( fig .\nthis minimal increase in life expectancy coincided with my appointment at thomas jefferson university as the associate director of the newly created adult sickle cell center .\nthe number of adults at that time was small and the transition from pediatrics to adult programs was at the age of 18 years .\nthe trickle of patients increased gradually and we were faced with adolescent and young adult african american patients who were in a state of confusion .\nstripped from the protective sphere of the pediatric world and the empathy of their pediatric hematologists and the pediatric ancillary staff , they were in a state of fear , anxiety , depression and , worst of all , severe pain .\nthe fact that most patients were barely educated , many without a high school degree , unemployed , mediocre health coverage , and dysfunctional family structure conferred a logarithmic dimension to the problem .\nthe arrow indicates the infliction point where life expectancy of patients with sickle cell disease began to increase .\nthe steady stream of admissions of patients with acute painful vaso - occlusive crises ( vocs ) to the emergency department ( ed ) and hospital were not welcome by most providers , hospital administration , the house and nursing staffs .\nthere was subtle resentment of the patients that sometimes extended to the hematologists who showed compassion to the patients . soon labels such as drug addicts , drug - seeking behavior , and hospital hopping and frequent flyer emerged .\nlistening to and believing the patients and keeping detailed records of ed and hospital admissions and the analgesics prescribed , revealed that most patients genuinely do not respond to a certain analgesic or a certain dose . increasing the doses of an analgesic or switching to another drug solved the problem in most patients .\naccordingly and with the approval of the institutional review board ( irb ) , i issued an identification wallet - sized , plasticized card that was carried by patients and presented to the provider treating their voc in the ed , hospital or any other medical facility .\ninformation printed on both sides of the card included : 1 ) demographic data and a recent photograph ; 2 ) hematological data including reticulocyte count ; 3 ) medical data including the type of scd , its complications and co - morbidities if present ; 4 ) all medications being taken by the patient and the recommended treatment of vocs including the name , dose , and the route of administration of the analgesics in question ; and 5 ) my name and contact information for answering questions if needed .\nit was not expensive to issue these cards . a polaroid camera available at that time and a laminator were the only equipments needed to issue these cards .\nlater on , information on the card was computerized and a printed copy was given to the patient .\nthe patients were very compliant in carrying it as faithfully as they carry their medical cards .\nsome providers liked it very much because it facilitated having a concise history about the patients .\nwhile this controversy was brewing , interesting developments in basic science were in progress to understand the pharmacodynamics and pharmacokinetics of opioids .\nin the 1970s , it was hypothesized that opioids have receptors to bind to and activate in order to relieve pain by blocking or minimizing the transmission of painful stimuli and raising the pain threshold .\nit did not take long after that to identify opioids as ligands that bind to stereospecific and saturable receptors in the central nervous system and other tissues [ 3 , 4 ] .\nin addition , recent elegant studies [ 6 - 10 ] have revealed a helical structure of the opioid receptors , which forms pockets in which the corresponding opioid ( ligand ) fits snugly ( fig .\nrecognition is highly specific , such that only l - isomers of certain opioids exert analgesic activity .\nphysiologically , by binding to receptors , opioids initiate a series of biochemical events including activation of g proteins , inhibition of adenylate cyclase , and extrusion of potassium ions , resulting in hyperpolarization of cell membranes [ 14 - 16 ] ; this delays or prevents transmission of painful stimuli .\nthus , the riddle why some patients respond to one opioid but not another had a pathophysiologic explanation .\n( a ) morphine - like molecule ( yellow ) in the deep pocket ( blue ) of the -opioid receptor . ( b )\n-opioid receptors from an intimate pair when crystallized with a ligand ( yellow ) such as morphine . knowing how an opioid molecule ( yellow ) sticks in the pocket of its receptor ( blue )\nparallel to the progress in the pharmacodynamics of opioids mentioned above , a concomitant advance in the pharmacokinetics of opioids was bubbling to the surface .\nphase i involves the cyp enzymes and phase ii metabolism conjugates the drug to hydrophilic substances , such as glucuronic acid , sulfate , glycine , or glutathione .\nmorphine , hydromorphone and oxymorphone are metabolized by glucuronidation , whereas the majority of the other opioids are metabolized by the cytochrome p450 isoenzyme system .\nthe net effect of an opioid depends on the availability of enzyme(s ) to convert it into metabolites that could be active or inactive .\nbriefly , the cyp2d6 genotypes are categorized into phenotypes based on the activity of the variant enzymes .\nultrarapid metabolizers ( ums ) have greater than normal activity due to duplication or triplication , of active alleles [ 20 - 23 ] , extensive metabolizers ( ems ) have normal enzyme activity , intermediate metabolizers ( ims ) have decreased enzyme activity , and poor metabolizers ( pms ) have absent or little enzyme activity .\npatients who are ums of fentanyl would rapidly convert it into inactive metabolites with minimal or absent analgesic effect requiring increasing the dose of fentanyl .\non the other hand , patients who are pms of fentanyl would experience prompt relief with relatively small doses of fentanyl but higher doses could be toxic due to the accumulation of unmetabolized fentanyl .\nthe cyp3a4 enzyme metabolizes more than 50% of all drugs ; consequently , opioids metabolized by this enzyme have a high risk of drug - drug interactions .\ntogether , current data on the pharmacodynamics and pharmacokinetics of opioids show great variability of genotypes among patients and extreme variability in individual responses to opioids . determining the pharmacogenetics profile of each patient\nfacilitates the choice of drugs that would be efficacious for that patient and avoid those drugs associated with harmful drug - drug interaction .\nthis approach in diagnostics and therapeutics ushers in the dawn of a new field for the management of individual patients based on their unique pharmacogenetics , phenotypic and biomarker characteristics .\nthis future approach is referred to as personalized medicine or , more recently , precision medicine .\nwe hope that this methodology would be approved and sponsored by the insurance companies for patients with scd . in the meantime , listening , believing and respecting the patient with sickle cell pain should be maintained for now as the approach to individualized therapy .", "answer": "in the 1970s , sickle cell pain was treated with trial and error approach by increasing or decreasing the dose of an opioid or switching from one analgesic to another . \n this approach was controversial with criticism and doubt about its usefulness . since then , advances in determining the structure of opioid receptors and the role of the cyp450 enzymes in metabolizing opioids revealed that these anatomic and metabolic findings are not the same in all persons , thus explaining the variability in response to opioids among patients . \n thus , the trial and error approach has a scientific basis after all .", "id": 207} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsince the first practical implementation of electrospray ionization ( esi ) with mass spectrometry reported by yamashita and fenn in 1984 , a number of different atmospheric pressure ionization ( api ) techniques have been developed .\nmany api techniques require extensive sample preparation as well as costly consumables to obtain mass spectra .\none of the most cost effective and widely available media for chemical separation and analysis is paper .\nit has been shown that an electro - osmotic flow similar to that of static electrospray can be utilized to interface a triangle of wetted paper to a mass spectrometer ( ms ) ; this form of analysis is called paper spray ( ps ) [ 49 ] .\nthe use of a chromatographic medium such as paper allows for the analysis of complex mixtures since separations will occur as the analyte is being driven along the paper medium .\nseparating analytes on a paper medium provides the benefits of reduced probability of ion suppression and rapid analysis .\nthe paper medium allows for analysis of complex samples such as biological tissue and dried blood spots which are not suitable for traditional infusion techniques due to their complex matrices [ 4 , 7 ] .\none limitation to ps , like many ms techniques that utilize incomplete chromatographic separations is the detector being utilized to perform the analysis .\nwhen dealing with complex samples or unknown samples , there is a need for high - quality data in order to determine what is being analyzed .\nfourier transform ion cyclotron resonance ( ft - icr ) mass spectrometers are powerful tools for analysis of complex mixtures due to their unsurpassed capability to obtain broadband high - resolution mass spectra with high mass accuracy . utilizing ps with a fourier transform ion cyclotron resonance ( ft - icr ) mass spectrometer as a detector allows for rapid analysis of both unknowns and/or complex mixtures . in this present work ,\nwe show the suitability of a 12 tesla ft - icr ms to obtain high - resolution broadband mass spectra utilizing a coffee filter paper spray medium .\nhigh - resolution mass spectra were first obtained for polypropylene glycol ( ppg ) and polyethylene glycol ( peg ) standards to test the source .\nsecond , urine and calf lung surfactant extract ( clse ) were analyzed to test the ps source for analysis of complex mixtures not suitable for direct infusion .\nall solvents used were hplc grade obtained from sigma aldrich ( st . louis , mo , usa ) .\nppg was obtained in the form of a tuning standard from applied biosystems ( bedford , ma , usa ) .\npeg standard was made by dissolving 1 mg of peg 2000 obtained from sigma aldrich ( st . louis , mo , usa ) in 1 ml of hplc grade water .\ncoffee filter , wegmans brand ( rochester , ny , usa ) , was cut by hand into an isosceles triangle with dimensions of approximately 5 mm ( base ) by 10 mm ( height ) . \n\nsamples for ppg and peg ps analysis were prepared by wetting the coffee filter triangle with 10 l of the standard solutions .\nthe wet filter paper samples were allowed to dry under ambient conditions before ps analysis was performed .\nmass spectra were then obtained by wetting the dried paper triangle with 10 l of 50 : 50 methanol : water and using the method described in section 2.5 .\n( amherst , ny , usa ) . prior to analysis , the sample was stored in chloroform in the refrigerator .\nsamples for clse analysis were produced by wetting a coffee paper triangle with 2 l of clse and allowing the sample to dry under ambient conditions before ps analysis was performed .\nmass spectra were then obtained by wetting the paper with 10 l of 50 : 50 methanol : water using the instrument method described in section 2.5 .\nurine samples were collected from two healthy adult males into sterile polypropylene centrifuge tubes ( vwr scientific ) and immediately placed in the freezer .\nthe samples were collected in accordance with the health sciences institutional review board at the university at buffalo ( hsirb no .\nprior to analysis , the samples were thawed to room temperature and 1 ml was pipetted into 2 ml sample vials ( agilent , santa clara , ca , usa ) for use .\nten l was injected directly onto a triangular coffee filter and allowed to dry under ambient conditions .\nonce dry , the filter paper was attached to the mass spectrometer via a copper clip and rewetted using 50 : 50 methanol : water for ps analysis using the instrument method described in section 2.5 .\nhigh - resolution spectra were obtained on a 12 t bruker solarix ft - icr ms ( bruker daltonics inc . ,\nthe positive potential was obtained by grounding the paper triangle using a copper clip and applying a negative voltage at the inlet to the mass spectrometer ( figure 1 shows an image of the source ) .\nmass spectra were obtained at various mass to charge ranges with a pre - ft - icr - trap hexapole accumulation time of 0.400 seconds and an ft - icr trap accumulation time of 0.025 seconds .\nall mass spectra were obtained in the positive mode at a spray voltage of 2 kv .\n polymeric standards were utilized to determine the suitability of ps with high - resolution ft - icr ms . in ft - icr ms the resolution of the mass spectra is relative to m / z as well as the number of data points that can be obtained during the detection process .\nhigh - resolution spectra require a time domain signal stable for longer than several hundred milliseconds .\npolyethylene glycol and polypropylene glycol produce a broad m / z range of ions ideal for testing the suitability of ps with high - resolution mass spectrometry .\nhigh - resolution mass spectra of peg and ppg are displayed in figures 2 and 3 , respectively .\nidentifies of the oligomer ion detected and their associated errors is given in tables 1 and 2 , respectively .\nsignal - to - noise obtained for peg and ppg after tuning spectra was in excess of 100/1 with absolute intensities that varied shot - to - shot by less than 20% .\nthis allowed ample time for adjustment of the filter paper towards the inlet of the mass spectrometer so as to optimize instrument setup and analysis .\nutilizing polymers of known m \n n values ( provided by the manufacturers ; polydispersity not given ) such as peg 2000 and ppg 2000 provides a detection window several hundred m / z wide for broad mass accuracy calibrations for ft - icr ms . \ncalf lung surfactant extract ( clse ) , which is commercially available in drug form as infasurf , is used to treat respiratory distress syndrome .\nclse is obtained by doing a total lipid extraction on the lavage fluid from a slaughtered calf lung [ 11 , 12 ] .\nphosphatidylcholine ( pc ) makes 79% of the molar distribution of lipids and consists of a choline head group attached to the phospholipid with varying degrees of unsaturation in the fatty acid chains .\nbased on the optimized setup determined from previously analyzing the standards , clse was then analyzed .\nps mass spectra of clse are given in figures 4 and 5 , and the identities with associated error provided in table 3 . \ndue to the complex nature of urine , many small molecules and metabolites were detected at varying intensities using ps with ft - icr .\nps mass spectra , showing numerous lipids and other metabolites obtained from the analyzed urine specimens of two healthy adult male subjects , are shown in figure 6 ; an inset of one of these ps mass spectra is shown in figure 7 while the other is shown in figure 8 .\na few of the metabolites identified in the 27-year - old volunteer using the exact mass capability of ft - icr are provided in table 4 .\nmetabolites identified in the 44-year - old volunteer using the exact mass capability of ft - icr are given in table 5 .\nof note , the 44-year - old volunteer , who was taking prescribed vitamin d supplements , showed indications of the vitamin d metabolite 25-hydroxyvitamin d2 - 25-glucuronide in the urine .\ninterestingly , both adult male subjects had indications of one or more glucuronides in urine .\nthis may signal a particularly strong propensity for glucuronides to ionize via the ps ionization mechanism ; this capability of ps should be further explored .\nwe developed a ps source for bruker ft - icr instrumentation that can be utilized for a broad range of chemical species .\nthe ps source was tested on a range of samples and determined the source was suitable for both polymer and biological samples .\nthe ps source provided an api medium for the analysis of complex mixtures while mitigating the possibility of cross contamination due to the disposable nature of coffee filter paper .", "answer": "paper spray ionization is an atmospheric pressure ionization technique that utilizes an offline electro - osmotic flow to generate ions off a paper medium . \n this technique can be performed on a bruker solarix fourier transform ion cyclotron resonance mass spectrometer by modifying the existing nanospray source . \n high - resolution paper spray spectra were obtained for both organic and biological samples to demonstrate the benefit of linking the technique with a high - resolution mass analyzer . \n error values in the range 0.23 to 2.14 ppm were obtained for calf lung surfactant extract with broadband mass resolving power ( m/m50% ) above 60,000 utilizing an external calibration standard .", "id": 208} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nautologous peripheral blood hematopoietic cell transplantation ( auto - pbhct ) is a well - established therapeutic option for patients with a variety of hematologic malignancies .\nmobilization of peripheral blood progenitor cells ( pbpc ) for auto - pbhct can be accomplished by using cytokines , most commonly granulocyte - colony stimulating factor ( g - csf ) , either alone or in combination with chemotherapy ( e.g. , cyclophosphamide , etoposide , cytarabine , etc . ) or plerixafor [ 1 , 2 ] .\nrecently reported phase iii studies have also shown superiority of the combination of g - csf with plerixafor over g - csf alone for mobilizing pbpc in patients with non - hodgkin lymphoma ( nhl ) and multiple myeloma ( mm ) [ 3 , 4 ] .\nplerixafor acts by selective and reversible antagonism of cxcr4 on cd34 + hematopoietic stem cells ( hsc ) .\nthis results in disruption of its interaction with cxcl12 ( formally sdf1 ) on bone marrow stromal cells , that cause a rapid release of stem and progenitor cells from bone marrow into peripheral blood .\nwhile plerixafor - based pbpc mobilization can circumvent the need for chemotherapy to mobilize cd34 + pbpcs , to our knowledge no prospective trials comparing plerixafor plus g - csf to chemomobilization have been published to date .\nlimited data on murine models suggest that a combination of plerixafor and chemotherapy may be more effective than the use of plerixafor alone for pbpc mobilization . despite the promising results of plerixafor and g - csf for pbpc mobilization in patients with mm and nhl [ 3 , 4 , 68 ] , the use of chemotherapy and g - csf - based regimens to mobilize pbpc remains standard practice in many transplant centers .\nthis decision is often influenced by a desire to improve collection yield , reduce mobilization failures especially in patients who are elderly , heavily pre - treated , and have poor bone marrow cellularity , and/or as an attempt to provide disease control [ 911 ] .\nlimited data are available on the preemptive use of plerixafor salvage in patients failing to collect adequate numbers of pbpc with chemotherapy and g - csf - based mobilization [ 1214 ] , and this topic has been reviewed recently .\nherein we report our experience from two north american transplant centers in a series of patients who received plerixafor salvage while failing chemotherapy and g - csf mobilization .\nfor patients undergoing chemotherapy and g - csf - based mobilization , it is standard operating procedure at both transplant centers to measure peripheral blood cd34 + cell count daily when the patient 's white blood cell ( wbc ) count recovers to 4,000/l or from day + 12 ( after chemotherapy ) onwards ( whichever occurs first ) .\npatients destined to fail pbpc chemomobilization were defined as ( i ) those with a peak peripheral blood cd34 + cell count of < 10/l following wbc count recovery ( wbc count of 4,000/l ) after chemotherapy - induced nadir or ( ii ) those who failed to collect at least 1 10 cd34 + cells / kg after two apheresis sessions . in these patients failing chemomobilization , we administrated plerixafor at a dose of 0.24 mg / kg subcutaneously 10 hours prior to apheresis in conjunction with g - csf ( 10 g / kg ) , as a preemptive salvage strategy . all collections were performed with a cobe spectra apheresis system ( caridianbct , lakewood , co ) , by processing three to four blood volumes .\nit is the institutional policy at both transplant centers to routinely target collection of 5 10 cd34 + cells / kg .\ndetermination of peripheral blood cd34 + cell count and cd34 + cell content of the apheresis product was performed at the georgia health sciences university hla laboratory and west virginia university hospitals flow cytometry laboratory .\nthe bd facscanto ii flow cytometer , ( becton dickinson , san jose , ca ) was used for all analyses .\nafter red blood cell lysis , washed samples were used for cd34 + enumeration with pe - labeled , 8g12 clone , immunoglobulin g1 ( becton dickinson , san jose , ca ) based on international society of hematotherapy and graft engineering ( ishage ) guidelines .\nthe final products were cryopreserved in 10% dmso using a controlled rate freezer and stored in liquid nitrogen .\nsuccessful mobilization was defined as a total of 2 10 cd34 + cells / kg patients body weight in the final product .\ndata was collected on mobilization and transplant outcomes through an electronic data base , prospectively maintained at each participating institution and analyzed utilizing spss version 13.0 .\npatient characteristics and transplantation outcomes of 16 patients who were failing chemomobilization ( as defined above ) and received preemptive plerixafor are summarized in table 1 .\npatients had received a median of two lines of therapies ( range 13 ) prior to pbpc mobilization . after recovering from chemotherapy - induced count nadir ( i.e. , wbc 4000/l ) , 15 patients had a peak peripheral blood cd34 + cell count of < 10 l .\nfive patients underwent at least 2 sessions of apheresis but were unable to collect 1 million cd34 + cells / kg .\nthese patients subsequently received a median of two doses of plerixafor salvage ( range 18 ) .\nthe median number of apheresis sessions was 3.5 ( range 27 ) , and the median number of cd34 + cells collected was 3.9 10 cells / kg ( range 2.47.8 ) . utilizing a cutoff of 2 10 cd34 + cells / kg , all patients who received plerixafor had a successful collection .\nnineteen percent of the patients were able to collect 5 10 cd34 + cells / kg .\nthree patients ( one with hodgkin lymphoma and two with nhl ) required more than four doses of plerixafor , but all eventually collected 2 10 cd34 + cells / kg .\nthe median peak peripheral blood cd34 + cell count prior to plerixafor administration was 3.5/l ( range 015 ) and increased to 6/l ( range 247 ) after the first dose of plerixafor ( p = 0.03 ) .\n93% of the patients had a peak peripheral blood cd34 + cell count of < 10/l before plerixafor salvage .\nfour patients had a peak peripheral blood cd34 + cell count of 1/l before plerixafor salvage .\nkinetics of peripheral blood cd34 + cell and wbc count changes after each dose of plerixafor for these 4 patients is shown in table 2 .\nafter transplantation , the median time to neutrophil and platelet engraftment was 10 days ( range 915 ) and 20 days ( range 929 ) , respectively . in order to identify predictors of response to plerixafor salvage ,\nas expected , patients with a higher peripheral blood cd34 + cell count at the time of the first plerixafor dose had a higher magnitude of change in their peripheral blood cd34 + cell counts ( r = 0.58 , p = 0.01 ) .\nonly three patients had a cd34 + cell count of 10/l before the first dose of plerixafor , and their median increase was 18/l compared to 6/l for patients who had peripheral blood cd34 + cell counts of < 10/l however , this difference was not statistically significant ( p = 0.3 ) .\nwe did observe a positive correlation between peak peripheral blood cd34 + cell count before the first dose of plerixafor and the total number of cd34 + cells collected at apheresis ( r = 0.62 ; p = 0.01 ) .\nof the 41 collections with plerixafor , the mean cd34 + cell dose collected was 0.79 10 cd34 + cells / kg from 25 collections in patients with a peripheral blood cd34 + cell count < 10/l versus 2.09 10 cd34 + cells / kg from 16 collections in patients with a cd34 + cell count greater than 10/l ( p = 0.001 ) .\ncorrelation analyses were performed in order to define an optimal cutoff of wbc count that can be used as a marker for the initiation of plerixafor salvage , which showed that wbc count had no correlation with a change in cd34 + cell count after the first dose of plerixafor ( r = 0.21 , p = 0.41 ) .\nutilizing the median wbc count of 32/l at the time of administration of plerixafor in our patients , we found that we were able to collect a higher number of cd34 + cells in patients who had a wbc count 32/l as compared to those with a wbc count > 32/l ( 1.67 10/kg versus 0.8 10/kg , p = 0.02 resp . ) .\nour limited multicenter outcomes data suggest that the addition of plerixafor as a preemptive salvage may rescue patients who are destined to fail chemotherapy and g - csf - based pbpc mobilization .\nin our series we used plerixafor salvage to rescue an otherwise failed attempt for chemomobilization , which contrasts with prior studies where plerixafor was used to remobilize patients who had failed prior mobilization attempts .\nthis is also in contrast to studies where plerixafor was routinely given to patients undergoing chemomobilization . in our series plerixafor\nwas given after recovery from chemotherapy - induced count nadir ( median of 11.5 days after chemotherapy ) and resulted in successful cd34 + cell collection in all patients , who were otherwise likely to fail chemomobilization .\ninterestingly patients with a wbc count of 32/l were able to collect a higher number of cd34 + cells .\nthis is in contrast to earlier data [ 1215 ] that indicated limited efficacy of plerixafor in patients with a lower wbc count .\nthis discrepancy can be a reflection of the decreased efficiency of the collection process in patients with a higher wbc count or possibly a reflection of timing of plerixafor administration .\ngenerally a cd34 + cell count of 1013/l is used as a cutoff for initiating apheresis following cytokine only , cytokine plus plerixafor , or chemomobilization in majority of transplant centers in the country . the median cd34 + cell count of our patients was only 3.5/l with 82% less than 10/l at the time of the first plerixafor dose , and all patients were able to collect a minimum of 2 10 cells / kg . however\n, a valid cutoff for peripheral blood cd34 + cell count to initiate apheresis when plerixafor is used as a salvage for failed chemomobilization is unknown .\npatient characteristics and institutional preference will likely continue to influence the choice for mobilization strategy in patients undergoing an auto - pbhct . while no prospective data are available to demonstrate better efficacy or cost effectiveness of plerixafor - based mobilization over chemotherapy - based mobilization , our preliminary data provide safety and efficacy data for plerixafor salvage to rescue patients failing chemotherapy - based pbpc mobilization .", "answer": "the combination of filgrastim ( g - csf ) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non - hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation . \n however , chemotherapy and g - csf - based mobilization remains a widely used strategy for peripheral blood progenitor cell collection . in this paper \n we describe our experience from two north american transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and g - csf mobilization . \n patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery . \n the use of plerixafor was associated with a 2.4-fold increase in peripheral blood cd34 + cell count and 3.9-fold increase in total cd34 + cell yield . \n all patients were able to collect 2 106 cd34 + cells / kg with this approach . \n these results were more pronounced in patients with a higher cd34 + cell count at the time of the first plerixafor dose . \n interestingly , peripheral blood white blood cell count was not shown to correlate with a response to plerixafor . \n our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization .", "id": 209} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nGenetic variation of fifteen folate metabolic pathway associated gene loci and the risk of incident head and neck carcinoma: The Women\\xe2\\x80\\x99s Genome Health Study\n\nPaper sections:\nIntroduction\nHead and neck carcinoma (HNC), the fifth most common cancer worldwide, is one of the most challenging conditions in clinical oncology owing to its resistance to therapy and high capacity to re-populate during treatment, thus posing a serious public health burden (1, 2). In addition to the well-reported risk factors, including advanced age, alcohol abuse and tobacco use, folate deficiency --an essential (antioxidant) vitamin that is present in fruit and vegetables-- has recently been associated with an increased risk of HNC (3\u20137). Altered folate metabolism contributes to carcinogenesis via mechanisms that impair DNA synthesis, replication, repair and methylation (7\u20139). Whether the importance of folate metabolism/deficiency in the underlying pathogenesis of HNC was modulated by genetic variation within the folate metabolic pathway (FMP) associated genes remains elusive (1, 2, 10).
To date, data from large prospective, epidemiological studies on examining the relevance of FMP associated genes as potential risk markers for HNC are scarce. We, therefore, examined the potential involvement of 203 tag-single nucleotide polymorphisms (tSNPs) in fifteen FMP genes (Supplementary Data Tables I and II) with (i) baseline plasma homocysteine (hcys) levels, and (ii) incident HNC, in a large prospective cohort of 23,294 initially healthy US Caucasian middle-aged women.
\n\nStudy design\nDetails of the study design have been previously described (11). In brief, participants in the Women's Genome Health Study (WGHS) \u2013a genetic substudy of the Women's Health Study (12, 13)\u2013 included initially healthy North American women aged 45 or older with no previous history of cardiovascular disease, cancer, or other major chronic illnesses. A baseline blood sample was collected during the enrollment phase of the Women's Health Study between 1992 and 1995. Study participants, who gave an informed consent for blood-based analyses related to risks of incident chronic diseases, were followed up for incident events that were adjudicated by an endpoints committee using standardized criteria and full medical record review (12, 13). The present investigation included 23,294 Caucasian participants of the WGHS; all were free of known cardiovascular disease and cancer at baseline. During a 15-year follow-up period, 55 cases of newly diagnosed HNC were identified. As described elsewhere, DNA extracted from the baseline WGHS blood samples underwent tSNP (r2 \u2248 0.80) genotyping using the genome-wide Illumina Infinium II Human HAP300 Duo \"+\" platform (14, 15). The Brigham and Women's Hospital Institutional Review Board for Human Subjects Research approved the study protocol.
\n\nStatistical analysis\nGenotype frequencies were compared with values predicted by Hardy\u2013Weinberg equilibrium using the chi-square test with one degree of freedom. Multivariable linear regression analysis, adjusting for age, and smoking status, was performed to assess the relationship of the tSNPs with baseline loge-transformed plasma homocysteine (lnhcys) levels. Hazard ratios (HRs) for association of each of the tSNPs with HNC were calculated separately by Cox regression analysis adjusting for age, smoking status, randomized treatment assignment, and further adjusting for baseline lnhcys levels and daily alcohol intake, assuming an additive model for genetic effects.
Haplotype estimation and inference were determined by expectation-maximization algorithm. Haplotype blocks were defined using the software Haploview v4.1. In addition, the relationship between haplotypes and HNC risk was examined by a referent (wild-homozygous) haplotype-based Cox regression analysis, adjusting for the same potential confounders/risk factors used in the single-SNP analysis. Only genes with 3 or more significant tSNPs (arbitrary cutoff) in the single-SNP analysis were further considered for a haplotype-based analysis. All analyses were carried out using SAS v9.1 package (SAS Institute Inc). A 2-tailed uncorrected p-value of 0.05 was considered a statistically significant result. Genotyping call rates were >99% per SNP.
\n\nResults\nThe baseline characteristics of the 23,294 initially healthy Caucasian women are shown in Table 1. Thirty-two out of the 203 SNPs evaluated were not in Hardy\u2013Weinberg equilibrium with uncorrected p-values <0.0500 (Supplementary Data Table I). In the multivariable linear regression analysis, a total of 42 SNPs (22 MTHFR, 8 MTR, 1 RFC1, 4 DHFR, 3 MTRR, 1 MTHFD1, and 3 TCN2) were differentially associated with baseline lnhcys levels (p-uncorrected <0.050; Supplementary data Table III). Results from the multivariable Cox regression analysis showed evidence for differential associations of 11 SNPs (1 MTHFR, 7 RFC1, 1 DHFR, and 2 TYMS) with HNC risk (p-uncorrected <0.050; Table 2). Supplementary Data Table IV presents the nominal (uncorrected) Cox regression results for all 203 SNPs evaluated. Further adjustment for baseline lnhcys levels, and alcohol intake showed virtually identical results (data not shown). Supplementary Data Figure I presents the linkage disequilibrium (LD) pattern of the tSNPs of RFC1 in the present sample population. The haplotype distribution (defined by Haploview v4.1) is shown in Table 3. Results from the haplotype-based analysis again showed an association of two Haploview-defined haplotypes of RFC1 with HNC risk (p-uncorrected <0.050; Table 3), consistent with the involvement of rs10033019. All SNPs evaluated were in agreement of proportionality hazard assumption.
\n\nDiscussion\nTo the best of our knowledge, the present prospective investigation is the first to examine the possible involvement of FMP genes in the risk of incident HNC, and we found -suggestive- evidence for an association of the genes evaluated, in particular, the replication factor C-1 (RFC1) gene locus.
Genetic variation within the FMP gene loci has been implicated in various forms of cancer including HNC (1). The FMP genes evaluated in the present study encode proteins for the complex one-carbon interconversion processes, which ultimately regulate and maintain genomic stability. Recent studies have demonstrated the effects of genetic variation within the FMP associated genes, in particular, MTHFR (C677T/rs1801133, A1298C/rs1801131, G1793A/rs2274976), MTR (A2756G/rs1805087), MTRR (A66G/rs1801394, C524T/rs1532268), SLC19A1 (A80G/rs1051266) in modulating risk of HNC (reviewed by Galbiatti and coauthors (1)). However, the present study found no association of the abovementioned gene variants with HNC risk (Supplementary Data Table III). Moreover, the present study confirmed an inverse relationship of MTR A2756G (rs1805087) (16\u201319), MTRR A66G (rs1801394) (20) with plasma hcys levels, and a null association of MTHFD1 G1958A (rs2236225) with HNC (21), as previously reported.
The present investigation, moreover, suggests that the replication factor C-1 (RFC1) gene variation may play a role in the underlying pathogenesis of HNC. Replication factor C (RFC) is an important factor involved in DNA replication, repair mechanisms, post-translational methylation as well as cell proliferation. Recent experimental investigation of the subunit 1 of Arabidopsis RFC (AtRFC1) -a homologue of p140, the large subunit of human RFC1- showed that AtRFC1 mutations caused defects in embryogenesis and led to embryo and seed abortion (22), suggesting that RFC1 may play a similar role in embryogenesis in humans, and its relevance to the congenital malformations caused by folate deficiency. Furthermore, using interaction cloning, Uchiumi et al. showed that the large subunit of replication factor C interacts with the DNA sequence repeats of telomeres and recognizes the 5-prime-phosphate termini of double-stranded telomeric repeats, thus suggesting that replication factor C may also play a role in telomere stability or turnover (23). Telomere instability, a hallmark of tumourogenesis, is widely demonstrated to play an important role in cancer development (24\u201326). Owing to the observed functional characteristics of RFC in relation to embryonic development (its relevance to congenital malformations due to folate deficiency), and telomere stability, the present findings encourage the need of further investigation into the possible involvement of replication factor C cascade, and the telomere-telomerase complex in the pathogenesis of HNC.
Strengths of the present study are the overall sample size, the prospective design and the complete long-term follow-up. Nonetheless, some potential limitations of our study require discussion. Our sample population was limited to Caucasian female healthcare professionals from the US. Thus, our results may not be generalizable to other racial/ethnic or socio-economic groups, geographical regions, or to males. Cautious interpretation of our present (uncorrected) findings should be exercised, and confirmation in other prospective studies is needed. Furthermore, pre-cancerous prediction of head and neck carcinoma based on SNPs analysis may be inadequate or low for clinical use (27).
In our study, we had the ability to detect, based on the present sample size, assuming 80% power, at an alpha of 0.05, an effect estimate of greater than 1.65 if the minor allele frequency is 0.50, and of greater than 3.50 if the minor allele frequency is 0.02, assuming a univariable-additive model. Thus, the present study may not have the power to detect a true low-to-modest risk of HNC associated with the gene variants tested.
In conclusion, if corroborated by other large, prospective investigations, the present data from a large cohort of apparently healthy Caucasian US females provide evidence for an association between the folate metabolic pathway associated gene variants tested, in particular, the replication factor C-1 gene locus and the risk of head and neck carcinoma.
", "answer": "Objective Recent studies have demonstrated the importance of folate metabolic pathway (FMP) in the pathogenesis of head and neck cancinoma (HNC). Whether the genetic variation within the FMP associated genes modulates HNC remains elusive. To date, prospective, epidemiological data on the relationship of FMP gene variation with the risk of HNC are sparse. Methods The association between 203 tag-SNPs (tSNPs) of 15 FMP associated genes (CBS, BHMT, DHFR, FOLR1, FOLR2, FOLR3, MTHFR, MTR, MTRR, MTHFD1, RFC1, SHMT1, SLC19A1, TCN2, and TYMS) and incident HNC was investigated in 23,294 Caucasian female participants of the prospective Women\\xe2\\x80\\x99s Genome Health Study. All were free of known cancer at baseline. During a 15-year follow-up period, 55 participants developed a first ever HNC. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and HNC risk assuming an additive genetic model. Haplotype-block analysis was also performed. Results A total of 11 tSNPs within DHFR, MTHFR, RFC1, and TYMS were associated with HNC risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis revealed an association of several prespecified haplotypes of RFC1 with HNC risk (all p-uncorrected <0.050). Conclusion If corroborated in other large prospective studies, the present findings suggest that genetic variation within the folate metabolic pathway gene loci examined, in particular, the replication factor C-1 (RFC1) gene variation may influence HNC risk.", "id": 210} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npica actually refers to the latin word for magpie , a bird thought to have odd feeding habits .\nincidence of pica has also been linked to iron and zinc deficiency . whether the pica is an eating disorder or obsessive compulsive disorder is still controversial .\nthe patient was a 27 year old young indian lady living in the baruipur with no previous psychiatric or medical history .\npatient complained of an unusual sensation in her abdomen for the last 3 months while her parents gave a history of habitual consumption of nails for the same duration .\nthe patient was a single child to her parents and she was living in the suburbs since her birth .\nshe had attended public schools and had completed her graduation on arts from a college in kolkata .\nsoon after her marriage , she expressed sexual aversion with history of dyspareunia . within a month of her marriage , she found it extremely difficult to live in her in - laws house and preferred to stay at her parental home , although her parents repeatedly insisted her to go back to her in - laws residence .\ndepressed and also admitted that for the last 3 months , she was having a sense of hopelessness and worthlessness over her future days .\nvanished. she temporarily enjoyed the gritty and spiky sensation of nails along her throat , but at night she used to have a vague abdominal sensation which she described to be \nfunny. according to her mother , she did not want to go back to live with her husband . on close interviewing of the patient , initially her response to same- sex relationship was guarded but later it was found that she was actually having such a relationship with another lady of her age for the past 3 years .\nshe also accepted that she used to consume glass piece occasionally since last 3 years but never disclosed them to anyone .\nshe had once had an x - ray of her abdomen done 2 years back due to complaints of low back pain which was inconclusive ; perhaps glass beads which are radiolucent were missed . no further investigation was done .\nthe patient was decently dressed in a pastel shade salwar with a boyish cut hairstyle . on mental state examination\non interviewing the husband , it was known they had never had any sexual intercourse since marriage .\non routine examination , possibility of iron deficiency anemia , serum ferritin abnormality and zinc deficiencies were ruled out .\nx ray of abdomen showed multiple radio opaque pointed objects in her gut ( ingested iron nails ) .\nthe patient had been nurtured in an overprotected environment by her parents in her early childhood days .\nhowever immediately following her high school , she had to take many responsibilities of the family all of a sudden because of loss of job of her father .\nshe was more bonded to her mother and in the elderly , often avoided her father because he was alcoholic .\nthe cultural , psychodynamic , and physiological aspect of this case is a unique one . the patient 's initial experimentation with ingestion of glass beads , though in a very remote sense , may be culture based considering the fact that the practice of ingesting such beads and sharp metallic objects has been reported .\nconsidering the fact that the patient was initially nurtured in an overprotected environment by her parents and suddenly being exposed to a comparatively hostile situation where she found a discouraging picture of the members of the opposite sex from that of her alcoholic father , the patient 's inclination toward same - sex relationship can be explained .\npsychologically , the inclination of the patient toward same sex relationship and her unfamiliarity and uneasiness with the members of the opposite sex led to marital dissatisfaction . also ,\nsince the patient had to take many burdens of her family at an age which may be considered quite an early one considering the indian standards and her socioeconomic profile , this probably has caused her to resort to some , harsh robust means like ingestion of nails which may have been an act to depict her \nher intelligent quotient as measured by wechsler 's adult intelligence scale had been found to be 98 which fall in normal age .\nas in most cases of pica , she initially did not come with a complaint of pica .\nrather , she had reported to the hospital with complaints of unusual sensation in her abdomen .\nthe present case presented a unique conglomeration of cultural , psychodynamic , and physiological determinants which together contributed to the expression of pica in comparison with previous reports and reviews . however , an interesting fact in this case is the age of the patient which is quite unusual for pica to occur .\nthis perhaps necessitates further research in dealing with the epidemiology and other aspects of this quite rare but interesting disease entity .", "answer": "pica has been considered as the ingestion of inedible substances or atypical food combinations . \n pica has been reported widely in pediatric age group and often found to be co existing with obsessive compulsive or major depressive disorder . \n reports of pica in elderly age group are relatively uncommon and rarely does it have an adult onset . in this article we present a case of adult onset pica . a young lady with unusual sensation in her abdomen \n was found to consume iron nails over years and there was history of dyspareunia since her marriage three months back . on query \n it was known that the lady is having same sex relationship over years . there \n unique conglomeration of cultural , psychodynamic and physiological determinants which together is responsible for this unusual habit of this lady . \n moreover the onset of the disease at a late age and different psychodynamic issues make the case all the more interesting . whether the pica is an eating disorder or \n obsessive compulsive disorder is still controversial . \n pica has been mentioned in diagnostic and statistical manual iv tr . \n the present case report warrants the need to look into this entity more closely with regards to its occurrence and etiology .", "id": 211} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncystic fibrosis ( cf ) is the most common autosomal recessive disorder among caucasians with an incidence rate of 1 in 2,500 individuals . the epithelial cells of several organs , including respiratory tract , exocrine pancreas , intestine , vas deferens , hepatobiliary system and also exocrine sweat glands are involved in cf .\ntherefore several clinical features , including suppurative lung disease , pancreatic insufficiency , neonatal bowel obstruction ( meconium ileus ) , multifocal biliary cirrhosis , absent vas deferens to malabsorbtive condition and growth retardation could be seen in affected patients [ 2 , 3 ] .\nhigh sweat electrolytes ( chloride and sodium ) concentration , which is seen in cf patients became basis for sweat chloride test since 1949 .\nthe measurement of sweat electrolyte concentrations was established as a standard procedure for diagnosis of cf and remained the gold standard test for the diagnosis of cf .\nthe diagnosis of cf could easily be made in the majority of cases based on typical clinical features and abnormal sweat chloride values . in such situations ,\ngenetic analysis of cystic fibrosis transmembrane conductance regulator ( cftr ) gene is not necessary .\nhowever , it may be useful in confirming the diagnosis , which also enables carrier testing and prenatal diagnosis [ 6 , 7 ] .\nthe universally accepted reference intervals for sweat chloride concentrations regardless of age or sex are > 60 mmol / l , which is considered diagnostic of cf ; 4060 mmol / l is considered borderline , whilst < 40\nin addition to sweat chloride concentrations , sweat sodium is also usually measured , as there is little difference between sweat sodium and chloride concentrations [ 810 ] in order to ensure accurate results from a quantitative sweat test using filter paper , a minimum sweat rate of 1g / m / min corresponding to 75 mg collected in 30 minutes is required ( for a 22 inch filter paper ) .\nconventionally , it takes around 45 minutes to collect proper volume ( 50400 mg ) sweat for accurate test , which makes the classic sweat test as a time consuming procedure .\nindeed many local laboratories in developing countries have not been approved to do the test for both techniques of sweat gathering and also electrolytes measuring . forming of salt crystallization of perspiration described by ferre calvete\net al could be considered as a useful and alternative test for easy detecting cf patients in these regions .\ntherefore , we designed this study to compare the results obtained by these two methods . in this study , 60 children with clinical signs suggestive of cf , who were referred to the children 's medical center , pediatrics center of excellence in iran , were investigated .\nthe study protocol was approved by the research ethics board of the childrens medical center , tehran university of medical sciences .\nclassic sweat tests ( gibson and cooke sweat test ) and crystallization test were performed for each subject for at least two times in the referral laboratory of the hospital .\nlocalized sweating was produced by iontophoresis of pilocarpine nitrate ( gibson and cook method ) using wescor gel discs [ 5 , 12 ] a copper electrode was then attached and a weak electrical current of about 3 milli - amperes ( ma ) was generated using a 9-volt battery for 5 minutes to stimulate sweating . immediately following stimulation ,\na preweighed filter paper was placed directly over the site of the positive electrode . at the end of the collection\nabout one hour later , the filter paper was removed and the weight was determined .\nthe test was repeated for two or three times in all subjects to confirm the results .\nmeanwhile one drop of each sample was put on lamella and heated by the light of microscope for 5 minutes .\nsixty children ( 29 females and 31 males ) with age range of 9 months to 2 years had taken part in this study .\nmeq / l , while it was 49.81meq / l in the male group without any significant difference between genders ( p>0.05 ) .\ncf was diagnosed for the remaining 29 patients who showed positive values of sweat classic test .\n1 ) , which provided the test with 100% sensitivity ( ci : 93.1100 ) . only one of 31 subjects without cf ( 17 males and 14 females ; aged 9 months to 2 years ) had positive crystallization test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) .\ncrystal formation in sweat sample of cystic fibrosis patients cystic fibrosis ( cf ) is one of the most frequent ( 1 in 2500 ) autosomal recessive diseases characterized by substantial clinical heterogeneity recent studies have begun to identify chromosomal locations that identify specific genes contributing to this variation . over the past several decades , there has been substantial progress toward diagnostic tools of cf .\ndetermination of chloride concentration in sweat is the current diagnostic gold standard for cf . \n \nthe conventional sweat test with elevated sweat sodium and chloride concentration after iontophoresis of pilocarpine is the standard laboratory test for cf .\nan accurate sweat test relies on coordination of several factors . technical error of instrument calibration and result reporting\nthe tests should be performed by expert personnel to ensure sufficient sweat volumes and proper use of equipment .\nthe centers doing such tests should follow standard guidelines to reduce complexity in interpreting a variety of result ranges [ 14 , 15 ] advanced equipments and experienced personnel which are necessary for accurate classic sweat test made this test unavailable for many centers , especially in developing countries .\nalthough sweat studies became standard diagnostic strategy for diagnosis of cf , it has some limitations whilst it may be unreliable due to not enough collected sweat or borderline values .\nindeed genetic studies to detect cftr mutation(s ) take time and may even find no useful information . therefore selecting the best cost - benefit method with high sensitivity and specificity\nis needed for diagnosis of cf . for this reasons nanoduct as a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes is also introduced as a reliable diagnostic tool .\nnanoduct has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion , diagnosis or suspicion of cf .\nsands and his colleagues indicated that simultaneous bilateral sweat testing with two different methods ( concentration and conductivity or nonoduct ) provides an extra quality control system , allowing more time efficient organization of the diagnostic and training procedures . \n \nforming of salt crystallization of perspiration seems as an attractive and alternative test for easy detecting cf patients . in this study , we have shown that looking for salt crystals in just one drop of sweat could diagnose cf , since crystal formation of sweat under light microscope was detected in a significant number of cf patients .\ncomparing these two methods of sweat test showed good positive predictive value of 96.7% and the negative predictive value of 100% with specificity and sensitivity of 96.7% and 100% , respectively .\ntherefore , the test could be a very useful alternative test , whenever the classic test is not accessible .\nsince the classic sweat test measuring chloride levels with the use of acceptable methods ( gibson - cooke or wescor macroduct ) should be performed in centers that conduct sweat tests frequently with properly documented controls , we recommend sweat crystallization test as an alternative test for cf diagnosis at least in areas where neither classic sweat test nor genotyping are accessible .\nlimitations : there were some limiting factors to consider in interpreting the study 's result .\nfirst , this study was conducted on a relatively small sample size . ideally , a larger and more popular sample size would perhaps delineate more suitable differences between the two methods of cf diagnosis in children with cystic fibrosis .\nsecond , this study compared two kinds of test in children whose first presentation was compatible with cystic fibrosis , although this would not be statistically a problem .\nas further study , comparing two methods of the mentioned tests between cf patients and normal children could be more helpful .\nthis study demonstrates the validity of sweat crystal formation test to support a diagnosis of cf in children whenever conventional sweat test is unavailable .\nin this study , 60 children with clinical signs suggestive of cf , who were referred to the children 's medical center , pediatrics center of excellence in iran , were investigated .\nthe study protocol was approved by the research ethics board of the childrens medical center , tehran university of medical sciences .\nclassic sweat tests ( gibson and cooke sweat test ) and crystallization test were performed for each subject for at least two times in the referral laboratory of the hospital .\nlocalized sweating was produced by iontophoresis of pilocarpine nitrate ( gibson and cook method ) using wescor gel discs [ 5 , 12 ] a copper electrode was then attached and a weak electrical current of about 3 milli - amperes ( ma ) was generated using a 9-volt battery for 5 minutes to stimulate sweating . immediately following stimulation ,\na preweighed filter paper was placed directly over the site of the positive electrode . at the end of the collection about one hour later , the filter paper was removed and the weight was determined .\nthe test was repeated for two or three times in all subjects to confirm the results .\nmeanwhile one drop of each sample was put on lamella and heated by the light of microscope for 5 minutes .\nsixty children ( 29 females and 31 males ) with age range of 9 months to 2 years had taken part in this study .\nmeq / l , while it was 49.81meq / l in the male group without any significant difference between genders ( p>0.05 ) .\ncf was diagnosed for the remaining 29 patients who showed positive values of sweat classic test .\n1 ) , which provided the test with 100% sensitivity ( ci : 93.1100 ) . only one of 31 subjects without cf ( 17 males and 14 females ; aged 9 months to 2 years ) had positive crystallization test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) .\ncystic fibrosis ( cf ) is one of the most frequent ( 1 in 2500 ) autosomal recessive diseases characterized by substantial clinical heterogeneity recent studies have begun to identify chromosomal locations that identify specific genes contributing to this variation . over the past several decades , there has been substantial progress toward diagnostic tools of cf .\ndetermination of chloride concentration in sweat is the current diagnostic gold standard for cf . \n \nthe conventional sweat test with elevated sweat sodium and chloride concentration after iontophoresis of pilocarpine is the standard laboratory test for cf .\ntechnical error of instrument calibration and result reporting are major factors that affect the results .\nthe tests should be performed by expert personnel to ensure sufficient sweat volumes and proper use of equipment .\nthe centers doing such tests should follow standard guidelines to reduce complexity in interpreting a variety of result ranges [ 14 , 15 ] advanced equipments and experienced personnel which are necessary for accurate classic sweat test made this test unavailable for many centers , especially in developing countries .\nalthough sweat studies became standard diagnostic strategy for diagnosis of cf , it has some limitations whilst it may be unreliable due to not enough collected sweat or borderline values .\nindeed genetic studies to detect cftr mutation(s ) take time and may even find no useful information . therefore selecting the best cost - benefit method with high sensitivity and specificity\nis needed for diagnosis of cf . for this reasons nanoduct as a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes is also introduced as a reliable diagnostic tool .\nnanoduct has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion , diagnosis or suspicion of cf .\nsands and his colleagues indicated that simultaneous bilateral sweat testing with two different methods ( concentration and conductivity or nonoduct ) provides an extra quality control system , allowing more time efficient organization of the diagnostic and training procedures . \n \nforming of salt crystallization of perspiration seems as an attractive and alternative test for easy detecting cf patients . in this study , we have shown that looking for salt crystals in just one drop of sweat could diagnose cf , since crystal formation of sweat under light microscope was detected in a significant number of cf patients .\ncomparing these two methods of sweat test showed good positive predictive value of 96.7% and the negative predictive value of 100% with specificity and sensitivity of 96.7% and 100% , respectively .\ntherefore , the test could be a very useful alternative test , whenever the classic test is not accessible .\nsince the classic sweat test measuring chloride levels with the use of acceptable methods ( gibson - cooke or wescor macroduct ) should be performed in centers that conduct sweat tests frequently with properly documented controls , we recommend sweat crystallization test as an alternative test for cf diagnosis at least in areas where neither classic sweat test nor genotyping are accessible .\nlimitations : there were some limiting factors to consider in interpreting the study 's result .\nideally , a larger and more popular sample size would perhaps delineate more suitable differences between the two methods of cf diagnosis in children with cystic fibrosis .\nsecond , this study compared two kinds of test in children whose first presentation was compatible with cystic fibrosis , although this would not be statistically a problem .\nas further study , comparing two methods of the mentioned tests between cf patients and normal children could be more helpful .\nthis study demonstrates the validity of sweat crystal formation test to support a diagnosis of cf in children whenever conventional sweat test is unavailable .", "answer": "objectivesweat chloride measurement is considered a standard diagnostic tool for cystic fibrosis ( cf ) . \n this study was performed to compare sweat chloride values obtained by quantitative pilocarpine iontophoresis ( classic test ) with sweat crystallization detected by direct observation of a drop of perspiration under light microscopy in patients with and without cf.methodsthe tests using both techniques were performed simultaneously in patients with and without cf . \n cutoff values of 60 mmol / l of chloride concentration for the classic sweat test was considered for diagnosis of cf . in crystallization method , \n observation of typical dendritic forms of salt crystals under light microscopy was interpreted positive.findingssixty patients suspected to cf ( 31 males and 29 females ) with age range of 9 months to 2 years underwent the sweat test using both techniques . \n median sweat chloride values was 26.13 + 10.85 in group with negative and 72.76 + 12.78 \n mmol / l in group with positive sweat test , respectively . \n all the patients who had positive sweat test in classic method showed typical dendritic forms of salt crystal in sweat crystallization test , which provided the test with 100% sensitivity ( 95%ci : 93.1100 ) . \n only one of the 31 subjects with negative results for classic sweat test had positive result for crystallization sweat test , which provided the test with 96.7% specificity ( 95%ci : 92.9100 ) . \n time spent to perform the crystallization test was significantly shorter than the classic method whereas its cost was also lower than the second method.conclusionthere was a good correspondence between two studied methods of sweat test . \n these results suggested the sweat crystallization test as an alternative test for detecting cf disease with high sensitivity and specificity .", "id": 212} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwaldenstrom 's macroglobulinemia ( wm ) is the result of a clonal proliferation of lymphocytes that produce monoclonal immunoglobulin m ( igm ) .\nit is now considered to correspond to lymphoplasmacytoid lymphoma as defined by the world health organization classification system ( 1 , 2 ) .\nmany central nervous system ( cns ) complications have been described in wm patients ; the majority have been associated with blood hyperviscosity caused by igm .\nthe hyperviscosity syndrome is characterized by headache , tinnitus , vertigo , blurred vision , and chronic bleeding from the nose and gums ( 3 ) .\nhowever , cns infiltration by plasmacytoid lymphocytes ( bing - neel syndrome ) has only rarely been reported ( 4 ) .\na 51-yr - old woman was diagnosed with wm three years prior to this presentation .\nshe received six courses of chlorambucil ( 0.3 mg / kg per day on day one to four orally ) and prednisone ( 45 mg / m per day on day one to four ) .\nnext , she received fludarabine chemotherapy ( 25 mg / m per day on day one to five intravenously ) with a limited response .\nhigh - dose cyclophosphamide and granulocyte colony - stimulating factor were administered to induce peripheral blood progenitor cell ( pbpcs ) mobilization for autologous stem - cell transplantation ; however , the number of pbpcs collected was not sufficient .\nwe then decided on a conservative treatment approach , because the patient did not have specific symptoms and the serum igm level was stable ( 3,000 - 3,500 mg / dl ) .\nthe laboratory values on admission were as follows : white cell count 8,050/l with normal differential counts , hemoglobin 9.6 g / dl , platelets 296,000/l , erythrocyte sedimentation rate 144 mm / hr , total protein 9.44 g / dl , albumin 2.85 g / dl , igg 3144.4 mg / dl , iga 25.4 mg / dl , igm\na brain computed tomography scan revealed multifocal extra - axial tumorous lesions along the dura matter .\na brain magetic resonance imaging showed an extra - axial soft tissue tumor along the left cavernous sinus and tentorium , right frontal convexity and tentorium and falx ; the brain parenchyma appeared to be unremarkable ( fig .\ncerebrospinal fluid analysis showed the following : white cell count 43/l with neutrophils 1% , lymphocytes 52% and monocytes 47% , total protein 1.81 g / dl , glucose 104 mg / dl , igm 64.5 mg / dl and a few plasmacytoid lymphocytes on cytology .\nstereotactic biopsy of dural tissue at the falx showed a diffuse infiltration with atypical cells , which were identified immunophenotypically as plasmacytoid lymphocyte with expression of lca ( + ) , cd3 ( - ) , cd20 ( + ) , and vs38a ( + ) ( fig .\n2 ) . the patient was confirmed to have cns infiltration by atypical plasmacytoid lymphocyte infiltration ( bing - neel syndrome ) .\nthe paitent received a total dose of 1,980 cgy with irradiation therapy of the whole brain that was administered in 11 fractions , and then her headache subsided , but the igm level was elevated persistently to 3,379.8 mg / dl . following radiation therapy ,\nfludarabine chemotherapy was performed ( 25 mg / m per day on 1 to 5 intravenously , two courses ) .\na follow - up brain mri after six months revealed a marked decrease in the size of the mass in the tentorium and falx ( fig .\nthe patient had no evidence of cns recurrence during the follow - up period of one year\n. however , the igm level has been increasing slowly , so further chemotherapy , including rituximab may be considered .\nin 1936 bing and neel reported the association of hyperglobulinemia , cns symptoms ( paresthesias , headache , and paralysis ) , and brain infiltration composed of plasma cells and lymphocytes in two patients ( 5 ) . in 1944 , waldenstrom described the syndrome that bears their name ( bing - neel syndrome ) ( 6 ) .\nthe bing - neel syndrome , originally placed in a \" toxic - infectious \" category , appears to be the result of involvement of the cns by diffuse neoplasm infiltration .\nalthough they are most often peripheral , they can involve the cns . in wm , the cns may be involved by a variety of mechanisms , including hyperviscosity and direct infiltration by neoplastic cells ( 7 , 8) .\npatients with bing - neel syndrome have sometimes presented with a mass containing neoplastic cells , but the masses have been intraparenchymal rather than meningeal ( 8 , 9 ) .\nthis syndrome can be subdivided into diffuse and tumoral forms . in the diffuse infiltrative form such as this case\n, malignant cells are localized mainly in leptomeningeal spaces , periventricular white - matter , pons , and medulla ( 7 , 10 - 12 ) .\nradiological findings in this syndrome have been reported , but a typical pattern has not emerged ( 13 - 15 ) . an imaging technique would be the preferable diagnostic test , although histological confirmation is necessary to establish the definitive diagnosis .\nintraventricular chemotherapy for bing - neel syndrome was reported to be effective in 1984 ( 15 ) .\nhowever , a review of the literature reveals that the outcome for most patients who underwent chemotherapy was poor , and the patients died within several months ( 10 , 13 , 14 ) .\ntherefore , patients with bing - neel syndrome may benefit from cranial radiation therapy prior to chemotherapy ( 9 , 12 , 16 ) .\nrecently , a great deal of interest has been noted by treatments with purine nucleoside analogs ( fludarabine , cladribine , and pentostatin ) because of their remarkable activity in lymphoproliferative disorders .\nit has been reported that a patient with bing - neel syndrome ( in its diffuse form ) was successfully treated with cladribine administration ( 17 ) , or radiation therapy and combination of cladribine , cyclophosphamide , and prednisone ( 18 ) . in the present case\nfurther treatment was not possible because of persistant bone marrow suppression . a follow - up brain mri after six months revealed a marked decrease in the size of the mass in the tentorium and falx ; the patient had no evidence of cns recurrence during the follow - up period of one year , but the igm level has been increasing slowly . we think that the major effect of deceased mass size was due to the radiation therapy in the present case .\nseveral retrospective and prospective studies have indicated that rituximab may induce an objective response in approximately 30 - 40% of previous treated patients with wm ( 19 ) .\nhowever , the effect of rituximab treatment on the cerebrospinal fluid b - cell compartment is limited in comparison with the effect on the b cells in the periphery ( 20 ) , and it has not been tried in bing - neel syndrome as yet . therefore , the effect of rituximab on cns involovement of wm need to be validated by of future studies .", "answer": "waldenstrom 's macroglobulinemia is an uncommon low - grade b - cell lymphoproliferative disorder in which monoclonal immunoglobulin m is produced . \n neurological symptoms due to hyperviscosity are frequent manifestations of waldenstrom 's macroglobulinemia . however , central nervous system infiltration by plasmacytoid lymphocytes ( bing - neel syndrome ) has only rarely been reported . \n we report a case of a 51-yr - old woman suffering from waldenstrom 's macroglobulinemia who complained of persistant headache . \n brain magnetic resonance imaging revealed an extra - axial soft tissue mass along the left cavernous sinus , left tentorium , right tentorium , and falx cerebri . a stereotactic biopsy of dural tissue from the falx was performed and showed plasmacytoid lymphocyte infiltration . \n the patient became symptom- free with irradiation of the whole brain followed by chemotherapy with fludarabine .", "id": 213} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nurinary tract infection ( uti ) is the most common infection contracted by renal allograft recipients . in patients of autosomal dominant polycystic kidney disease ( adpkd )\n, cyst infection presents a complex diagnostic and therapeutic challenge , especially in the post transplant period .\nconsequently , early and reliable detection of infected renal cyst is crucial for optimal patient management , especially when initial antibiotic therapy has failed .\nit has been infrequently reported in the post transplant scenario or in the adpkd patients .\nwe report a case of post transplant xpn in the native adpkd kidney presenting as relapsing uti .\n18-fluorodeoxyglucose ( fdg)-positron emission computerized tomography ( pet / ct ) scan allowed the exact localization of the infection in the renal parenchyma and guided the therapeutic procedure with subsequent resolution of uti .\na 53-year - old male of adpkd - ckd on maintenance hemodialysis since one and half years received a deceased donor renal transplant at our institute .\nhis postoperative recovery was uneventful and he was discharged on tenth post transplant day with a serum creatinine of 1.2 mg / dl .\nhe presented two weeks later with complains of fever , malaise and dysuria . on clinical examination , he was hemo - dynamically stable but febrile .\nlaboratory parameters included hemoglobin 10.2 gm / dl , leukocytes 8,600/cmm , platelets 2.9 lacs / cmm , glucose 186 mg / dl , urea 18 mg / dl , serum creatinine 1.7 mg / dl , sodium 138 meq / l , potassium 4.3 meq / l .\nurine analysis showed , albumin 1 + , 40 - 50 leukocytes /high power field ( hpf ) , red cells 4 - 5/hpf , no casts , bacteria , acid fast bacilli or fungus were found .\nchest x - ray was normal , abdominal ultrasonography showed multiple hepatic and renal cysts in native kidneys , but was not suggestive of any infection , graft kidney was unremarkable .\nhe was treated with antibiotics and responded well to the same and later discharged . over the next three months patient presented twice with symptoms of uti and the urine cultures on both occasions grew escherichia coli .\nhe was evaluated with ultrasonography and unenhanced computerized tomography ( ct ) , which revealed a normal transplant kidney and multiple cysts without evidence of any infection , hemorrhage or calculi in native kidneys .\nsubsequently , patient underwent cystoureteroscopy with bilateral selective urine sampling from native kidneys , however culture revealed no growth . in an attempt to localize the source of infection\nit showed hyper - metabolic lesion arising in postero - inferior part of right native kidney [ figure 1 ] .\npet / ct guided aspiration reveled purulent fluid , culture of the same yielded heavy growth of e. coli . on the basis of these findings , patient was subjected to right native kidney nephrectomy .\nthe cut section of the gross specimen showed xanthomatous area [ figure 2 ] and the histopathology was suggestive of xpn [ figure 3 ] .\npatient made a good recovery with s. creatinine returning to 1.3 mg / dl and urine culture being sterile on subsequent follow - up of three months .\npet / ct scan showing strong fdg uptake into postero inferior part of right native kidney ( arrow ) gross section of right kidney showing xanthogranulomatous area ( arrow ) light micrograph showing an interstitial infiltrate composed of neutrophils , mononuclear cells , and , most characteristically , lipid - laden macrophages ( arrow ) .\nfebrile illness owing to complicated uti 's secondary to renal or hepatic cyst infection is a common cause of graft dysfunction .\nif not localized early and redressed they can be a source of significant morbidity especially in an immuno - compromised host .\nit is characterized by replacement of renal parenchyma with diffuse or segmental cellular infiltrate of lipid laden macrophages called foam cells .\nhere , we report a case of rare occurrence of xpn in native polycystic kidney of a renal allograft recipient . in the literature ,\nxpn in adpkd either in transplant scenario or otherwise has been infrequently reported.[46 ] in our case , conventional ct scan was non - contributory , however fdg pet / ct scan was helpful in localizing the site of infection .\nas the patient was not responding to conservative management it was decided to proceed with nephrectomy of infected kidney .\nxpn was subsequently established on evaluation of gross specimen [ figure 2 ] and histopathology [ figure 3 ] .\nfdg pet / ct scan in the recent times has emerged as a valuable tool for the transplant physician in localizing of infections especially in adpkd patients .\npet / ct can overcome interpretive challenges in identifying tissue infection , based on the high metabolic activity and increased uptake of the glucose - analogue fdg by inflammatory cells .\npost transplant , uti especially in the adpkd patients is challenging to the transplant physician .\nthis case highlights the rare occurrence of xpn as a cause of post transplant uti , especially in the absence of obstruction or stone disease .\nfdg pet / ct imaging is a valuable tool in both localization and subsequent planning of therapeutic interventions for complicated utis associated with adpkd transplant patients .", "answer": "urinary tract infection ( uti ) is the most common infection contracted by renal allograft recipients . in patients of autosomal dominant polycystic kidney disease ( adpkd ) \n , cyst infection presents a complex diagnostic and therapeutic challenge especially in the post transplant period . \n accurate diagnosis forms the cornerstone in salvaging the graft from potentially catastrophic outcome . \n we describe a case of xanthogranulomatous pyelonephritis ( xpn ) in the native kidney in a patient of post transplant adpkd which presented as frequently relapsing uti with graft dysfunction where in accurate diagnosis was made possible with the aid of 18-fluorodeoxyglucose ( fdg ) - positron emission computerized tomography ( pet / ct ) .", "id": 214} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfrontalis sling surgery is the treatment option for myopathic blepharoptosis with poor levator muscle action .\nnontuberculous mycobacterial infections in the periocular region are rare and are usually caused by organisms belonging to runyon group iv including mycobacterium chelonae and mycobacterium fortuitum .\nchang et al . reported six cases of nontuberculous mycobacterial infection and found an association with nasolacrimal duct obstruction , implantation of foreign body , history of recent surgery , and immunosuppression .\nmauriello found implantation of a foreign body in 5 out 13 patients of nontuberculous mycobacterial infections of the periocular region .\ntreatment of nontuberculous mycobacterial infections can be difficult because of their multi - drug resistance .\ntreatment usually involves surgical debridement with removal of infected foreign body and a prolonged course of antibiotics like amikacin , clarithromycin , ciprofloxacin , and doxycycline .\nwe report a rare case of nontuberculous mycobacterial infection of the silicone rod after frontalis sling surgery .\na 65-year - old apparently healthy male presented with complaints of pain and swelling of both eyelids of 2 months duration .\nhe had undergone cataract and frontalis sling surgery for myopathic blepharoptosis in both eyes 2 years prior to presentation .\nthe best corrected visual acuity for distance was 20/400 in right eye and 20/25 in the left eye .\nexamination of face showed multiple , erythematous nodules involving both upper eyelids and the brow .\nall nodules were localized to the scars from the previous ptosis surgery with a few showing signs of suppuration ( fig . \nthe posterior segment showed hypertensive retinopathy in both eyes and a scar at the macula in the right eye .\nsystemic workup was unremarkable and included a complete blood picture , chest x - ray and serological tests for hiv .\nthe patient was clinically diagnosed to have chronic progressive external ophthalmoplegia status post bilateral frontalis sling and cataract surgery with multiple abscesses in forehead and upper eyelids .\nthe patient underwent an incision and drainage of the abscesses in the brow and the purulent material was sent for microbiological examination .\nthe smear showed the presence of acid fast bacilli on 20 % acid fast staining ( fig . \n1b ) and culture was significant for staphylococcus sp . and m. fortuitum ( fig . \nthe patient received intravenous amikacin ( 1 g / day , single dose ) and ciprofloxacin ointment locally .\npoor response to treatment necessitated exploration with explantation of the silicone rod sling in the right eye 10 days later .\na repeat microbiological evaluation showed acid fast bacilli and significant growth of m. fortuitum on culture .\nas the isolate showed a similar antibiotic sensitivity pattern the patient was continued on intravenous amikacin ( 1 g / day ) .\nhowever , 11 days later , the patient suffered from another episode of pain and swelling in the left eye .\na repeat exploration of the brow with drainage and silicone rod explantation was performed in the left eye .\nthe patient showed a slow but definite improvement and received intravenous amikacin for 6 weeks .\nfive months after commencement of therapy the patient was asymptomatic and the left upper eyelid position was maintained ( fig . \n1a an apparently healthy 62-year - old man presented with painful , erythymatous nodules of bilateral brow and upper lids two years after frontalis sling surgery for severe myopathic ptosis .\nb microscopic picture of the purulent material showing long , slender acid fast bacilli along with polymorphonuclear cells ( ziehl neelsen stain , total magnification 1,000 ) .\nc sheep blood chocolate agar inoculated with purulent material along with silicone tube ( left eye brow after 11 days of treatment ) shows confluent growth of cream colored , opaque , medium size colonies of staphylococcus aureus and tiny , semi - opaque colonies of mycobacterium fortuitum ( incubation : 4 days , 5 % co2 , 37 c ) .\nd five months after sensitivity - based antibiotic treatment and explantation of bilateral silicone rods , the patient showed resolution of symptoms .\nthe left upper eyelid maintained an elevated position after silicone rod explantation a an apparently healthy 62-year - old man presented with painful , erythymatous nodules of bilateral brow and upper lids two years after frontalis sling surgery for severe myopathic ptosis .\nb microscopic picture of the purulent material showing long , slender acid fast bacilli along with polymorphonuclear cells ( ziehl neelsen stain , total magnification 1,000 ) .\nc sheep blood chocolate agar inoculated with purulent material along with silicone tube ( left eye brow after 11 days of treatment ) shows confluent growth of cream colored , opaque , medium size colonies of staphylococcus aureus and tiny , semi - opaque colonies of mycobacterium fortuitum ( incubation : 4 days , 5 % co2 , 37 c ) .\nd five months after sensitivity - based antibiotic treatment and explantation of bilateral silicone rods , the patient showed resolution of symptoms .\nseveral authors have reported about nontuberculous mycobacterial infections after periocular surgery [ 3 , 4 ] .\nthe median time interval between prior surgery and onset of infection in these reports was 6 weeks ( range 0.511 months ) [ 3 , 4 ] . in our patient , multiple erythematous nodules with suppuration along the tract of the silicone rod more than 2 years after surgery led to the suspicion and eventual diagnosis of nontuberculous mycobacteria . some aspects in our patient need to be highlighted .\nfirst is that a bilateral infection by nontuberculous mycobacteria involving the silicone rod after frontalis sling surgery has not been reported earlier .\nthe lodgement of nontuberculous mycobacteria in the brow region in our case may be related to the persistent irritation from the silicone rod and its predeliction for fat [ 4 , 5 ] .\nsequestration of nontuberculous mycobacteria with fat allows its growth without detection by normal immunosurveillance [ 4 , 5 ] . in our patient ,\nsequestration of nontuberculous mycobacteria in the brow fat may have been responsible for delayed and bilateral infection involving the silicone slings .\nfurther , fitzgerald et al . found nontuberculous mycobacteria in 82 % of fat globules in their series of 71 cases .\ncomplete resolution in our case occurred only after silicone slings were removed from both eyes .\nfinally , removal of the silicone sling did not result in a recurrence of blepharoptosis .\nthis phenomenon is postulated to be due to scarring and fibrosis along the tract of the silicone rod .\nnontuberculous mycobacterial may be responsible for bilateral delayed infection after frontalis surgery with silicone slings in an immunocompetent adult .\nsurgical removal of infected slings and prolonged course of antibiotics are required for complete resolution .\nthe authors do not have any financial interest or any conflicting relationship in any of the issues or products referred to in the manuscript .\nthis article is distributed under the terms of the creative commons attribution license which permits any use , distribution and reproduction in any medium , provided the original author(s ) and source are credited .", "answer": "purposethe purpose of this study is to report a case of nontuberculous mycobacterial infection after frontalis sling surgery.methoda 65-year - old man presented with bilateral painful , erythematous lesions in the brow and upper eyelids . \n he had a history of frontalis sling surgery for myopathic ptosis 2 years back and all lesions were found localized to the tract of the silicone rod used in the previous frontalis sling surgery.resultincision and drainage of the lesions with microbiological analysis revealed significant growth of coagulase negative staphylococcus and mycobacterium fortuitum . \n sensitivity - based antibiotic treatment with intravenous amikacin was started , but poor response necessitated eventual explantation of both silicone rods for relief of symptoms . \n culture of the explanted rods revealed similar results of m. fortuitum infection . \n five months after the acute presentation , the patient is asymptomatic.conclusionnontuberculous mycobacterial infection may be a delayed onset complication in frontalis sling surgery using silicone rods .", "id": 215} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngenome - wide association ( gwa ) analysis has provided the first effective strategy to allow a systematic dissection of the genetic basis of common , complex , multifactorial traits .\nalthough for many of these we remain some distance from a complete enumeration of causal mechanisms , there have already been substantial advances in understanding of disease - the role of autophagy in inflammatory bowel disease and cell adhesion in autism , for instance . however , for most common traits the proportion of the overall phenotypic variance explained remains small , limiting the extent to which prediction of individual disease risk is possible .\nthere is growing speculation about the mechanisms that might account for the substantial proportion of trait heritability that remains to be characterized .\nthis speculation has repercussions well beyond recondite theoretical discussion about the genetic architecture of complex traits .\nwith advances in technology ( particularly next - generation sequencing ) and growing enthusiasm for funding large - scale gene discovery efforts , hypotheses about the nature of this so - called ' genetic dark matter ' have a direct bearing on research strategies .\nrecently , this debate has seemed increasingly polarized between those who feel a continued search for common susceptibility variants is of limited value , because all that remains to be found are variants of vanishingly small effect , and those who feel that , pending reductions in costs that will allow high - quality , whole - genome sequence data to be generated in adequately powered sample sizes , there is virtue in persisting with an approach of proven worth .\nthere is good reason to assume that this ' dark matter ' is neither an illusion created by inflated estimates of heritability nor the consequence of marked non - additivity of effects .\nif so , then the sum total of genetic variance should largely be explicable in terms of the main effects of all the risk alleles of various types ( single nucleotide polymorphisms , indels , copy number variants ( cnvs ) and inversions ) , allele frequencies ( rare , low - frequency and common ) and effect sizes .\nso far , the only parts of this ' space ' explored systematically are those occupied by rare , penetrant alleles ( principally through linkage analysis of monogenic phenotypes ) and common , mostly low - effect alleles ( accessible through gwa analysis ) .\nas we seek to make sensible decisions about the direction of future discovery efforts - in terms of the characteristics of the variants we are seeking and the technologies we should use to find them - we need to understand what the exploration of the ' known ' genetic landscape can tell us about the parts that remain largely uncharted .\none long - standing view is that complex trait susceptibility is predominantly a matter of common variants .\ncommon variants collectively account for most individual variation in dna sequence , and the same might be expected to be the case for phenotypic variation .\nif true , the results of gwa studies so far indicate that most of the as - yet - undiscovered variants must ( in europeans at least ) have very small effects , because the high coverage and large sample sizes used will have left few , if any , large common - variant effects undiscovered .\nevidence ( for example , from large - scale meta - analyses ) is , for many traits , consistent with the notion of a long ' polygenic tail ' of small effects , but it remains unclear how much of overall heritability can be explained under this model .\nthe idea that complex - trait susceptibility involves a very large number of variants of modest effect has led some to suggest that the value of all such discoveries is diminished , on the basis that one learns little about the biology of disease if too many genes are implicated . however , for many phenotypes , the overall salience of the loci of greatest effect emerging from gwa studies ( the pathways implicated and the relationships to monogenic forms of the same traits ) argues forcefully against such a nihilistic interpretation .\nthe contrasting viewpoint holds that common - trait susceptibility derives mostly from the action of rare or low - frequency variants .\nalthough such variants account for less individual sequence variation than common variants , there may be a disproportionate effect on disease susceptibility .\nthe more recent origin of low - frequency variants may allow alleles with more dramatic phenotypic effects to be represented in the population . also , large - effect alleles may cause phenotypic disturbances that are not as easily buffered by compensatory changes during development as are well tolerated , small - effect , common - variant alleles .\nrecent evidence that large , rare cnvs are associated with behavioral and psychiatric disease phenotypes supports this view .\nsome argue that such a rare variant architecture is precisely what one would expect for diseases causing low reproductive fitness , though this rationalization fails to explain the high yield of common - variant signals reported for other diseases , such as type 1 diabetes , that were , until recently , fatal during early life .\nit has even been suggested that many of the common - variant associations discovered by recent gwa studies may turn out to be due to the concerted action of multiple low - frequency and rare causal variants .\nthe nod2 ( card15 ) signal for crohn 's disease indicates that this is certainly possible . for many diseases ,\nhowever , evidence that common - variant associations are consistent across multiple ethnic groups represents a strong counter to such a model : one would expect the linkage disequilibrium patterns around recent rare and low - frequency causal variants to result in far more inter - ethnic heterogeneity than is actually observed .\nalthough both extreme positions have merit , the likelihood is that , for most diseases , the architecture of predisposition features causal variants that have a wide range of allele frequencies and effect sizes . for most complex traits\n, the absence of compelling signals from linkage studies conducted in families segregating multifactorial diseases imposes an upper bound to feasible effect sizes ; even so , it is easy to show that a limited number of low - frequency susceptibility alleles of medium effect could go a long way to explaining missing heritability .\nfor example , the effect of a low - frequency variant with a population minor allele frequency of 1% and a per - allele odds ratio of 3 , when measured in terms of sibling relative risk ( a commonly used measure of familial aggregation ) , exceeds that of the largest common - variant effect known for type 2 diabetes ( around tcf7l2 ) .\ntwenty such variants across the genome would account for most of the unexplained heritability for this condition .\nsuch a constellation of variants could provide a respectable tool for individual disease prediction , and the variants discovered would ( because of their relatively large effect size ) be valuable resources for detailed molecular and physiological study\n. the extent to which variants with these characteristics are segregating in the population remains unknown , but this is an area in which the combination of next - generation sequencing technologies and large - scale association analysis provides a powerful stimulus to discovery .\nearly results of this approach ( such as the identification of low - frequency variants within the ifih1 gene that have a marked effect on type 1 diabetes susceptibility ) are encouraging .\nultimately , we can expect large - scale , high - depth , genome - wide sequencing to enable the systematic exploration of the entire allele - frequency , effect - size space and provide empirical resolution of many of these issues .\nhowever , there remain serious financial , logistical and analytical barriers to the implementation of this technology , and the number of such experiments that could be supported by the major funders is , for the time being , limited .\nall this means that , for the next few years , the power of next - generation sequencing will need to be used carefully if a profusion of underpowered discovery efforts is to be avoided .\nefforts targeted to specific genomic regions ( around particular candidate genes or pathways or exons across the genome , for example ) are attractive because high coverage of the selected areas in large sample sizes can be generated at reasonable cost .\nwhole - genome sequencing will , for now , be restricted to low - pass coverage across respectable sample sizes , or high - depth coverage in smaller , highly selected , phenotypically extreme sample sets .\nthe genomic distribution of disease - effect loci will have a major impact on the success of these alternative approaches ( figure 1 ) .\nif the low - frequency and rare variants influencing a given trait are disproportionately located in the same loci as the common variants that have been found to date , then targeted follow - up of regions revealed by gwa studies will be a powerful approach , and extending the range and scope of gwa analysis ( to other ethnic groups , for example ) should be a particularly efficient strategy . if , on the other hand , the ' dark matter ' variants have little positional ( or biological ) overlap with those already known , then genome - wide resequencing is likely to be the only practical way to find them .\nthe evidence so far ( overlap between monogenic and multifactorial loci ; growing numbers of loci with multiple independent association signals ; extensive pleiotropy , and so on ) provides some support for the former view .\neffort in tracking down common susceptibility variants , as well as being valuable in its own right , should therefore guide researchers towards other types of causal variants .\ntwo possible versions of the state of nature are presented ( see text ) . in one ( ' even ' ) , causal variants differing in terms of allele frequency ( color scale ) and effect size ( height of bar ) are distributed randomly across the genome : the location of common - variant ( red / orange ) associations of modest effect provides no guide to the location of lower - frequency variants ( yellow / green ) , some of which have quite large effects . in the other ( ' lumpy ' ) , causal variants congregate around certain genomic positions ( ' genes ' ) : gwa studies that reveal the location of the common - variant associations will also reveal the positions of lower - frequency variants , and the proportion of disease biology explained by the loci discovered through gwa studies will be far greater than the proportion of variance explained would suggest .\nwith only limited empirical data to guide future locus - discovery efforts , extrapolation from the modest proportion of genetic variance so far explained is fraught with danger .\nthe menu of possible research strategies is large , but each choice makes some implicit assumption about the characteristics of the variants being sought and the genomic architecture of the disease under consideration . given uncertainties over the true state of nature , it is difficult to say which approaches will be most productive .\nthis argues for open minds , a healthy disdain for orthodoxy , and careful exploration of the technological and methodological options . at the same time\n, it is important that the next wave of large - scale discovery efforts is designed so as to test assumptions about trait architecture and technological performance so that lessons of generic value to the field can be learned .\ni thank the many colleagues around the world who contributed to the discussions that informed this article .", "answer": "identification of common - variant associations for many common disorders has been highly effective , but the loci detected so far typically explain only a small proportion of the genetic predisposition to disease . \n extending explained genetic variance is one of the major near - term goals of human genetic research . \n next - generation sequencing technologies offer great promise , but optimal strategies for their deployment remain uncertain , not least because we lack a clear view of the characteristics of the variants being sought . here \n , i discuss what can and can not be inferred about complex trait disease architecture from the information currently available and review the implications for future research strategies .", "id": 216} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneonatal diabetes mellitus ( ndm ) is a rare monogenic form of diabetes starting within the first 6 months of life 13 .\nthe disease has an incidence of about 1:100,000260,000 live births and can be permanent ( pndm ) , requiring lifelong treatment , or may be transient ( tndm ) , in which case the diabetes may spontaneously remit ( or be so mild as not to require treatment ) , but will often relapse , usually during adolescence 35 .\na genetic diagnosis has been made in up to 90% of these patients 7 . in the majority of them\n( around 70% ) , it was found that a genetic or epigenetic alteration in the tndm locus on chromosome 6q24 causing the overexpression of two imprinted genes 7 .\nless frequently , activating mutations of the genes kcnj11 and abcc ( accounting for 10% and 13% of the cases , respectively ) may result in tndm 7 .\nmutations in these genes lead to a gain - in - function of the pancreatic atp - sensitive potassium ( katp ) channel , which is critical in the regulation of insulin secretion by the beta cell 3,6,8,9 .\nthe beta cell katp channel is an octameric complex composed of four pore - forming subunits : channel - building inwardly rectifying potassium - channel subunits ( kir6.2 ) encoded by the kcnj11 gene , and four regulatory sulfonylurea - receptor subunits ( sur1 ) and encoded by the abcc8 gene 10,11 .\nthese subunits regulate the metabolic activity of the channel , which is shut down in response to an increase in intracellular atp , leading to insulin secretion .\ngain - in - function mutations of either of these genes keep the channel in open conformation and impair insulin secretion 1012 .\nmost patients with kcnj11 mutations treated with insulin can be transferred to sulfonylurea ( su ) with a remarkable improvement in metabolic control and patient 's quality of life 13 .\nsulfonylureas close katp channels , through an atp- independent route , improving insulin secretion and representing a suitable therapeutic alternative for patients with kcnj11 mutations 10 . for these reasons ,\nidentification of katp channel mutation can have a major impact on the treatment 's choice .\nthis is an example about how molecular diagnosis can influence the clinical management of the patients .\nherein , we report on a case of ndm in a caucasian boy , who presented severe diabetic ketoacidosis ( dka ) at 17 days of life .\nthe genetic screening showed a heterozygous missense mutation ( c.679 g > a ) in the kcnj11 gene which leads to the replacement of lysine with glutamic acid at position 227 ( e227k ) of the atp sensitive potassium channel .\nan 11-day - old caucasian boy was admitted to the neonatal care unit with complaints of poor weight progression , suppurative conjunctivitis , and mucoral candidiasis .\nhe was the second child of a 21-year - old woman ( gravida 2 , para 1 ) without history of diabetes , and was born through cesarean section at 38 weeks of pregnancy due to preeclampsia .\napgar score was 5/9/10 ; birth weight was 2890 g ( p15 ) , length 47 cm ( p15 ) and head circumference 34.5 cm ( p50 ) 14 . on physical examination ,\nthe infant exhibited axial hypotonia and weak suction reflex , demanding a nasogastric tube in order to be feed . at 17 days\nthe child became irritable , drowsy , dehydrated , tachypneic , tachycardic with poor peripheral perfusion ; rectal temperature was 37.8c .\nhe was started on intravenous vancomycin after isolation of a methicillin - resistant staphylococcus from the axillary suppurative adenitis .\nblood tests revealed a glycemia of 1412 mg / dl with high levels of ketonemia ; serum sodium was 172 \nmmol / l ; potassium 3.9 mmol / l , and the ph was 7.0 .\nafter initial treatment with intravenous 0.9% saline serum , he was started on intravenous insulin perfusion ( 0.01 u / kg / h ) in a 0.45% saline serum supplemented with 15 meq / l of potassium chloride .\nthree days later , the insulin perfusion was stopped and the child was transferred to a subcutaneous protocol of intensive insulin therapy , consisting in a once daily administration of insulin glargine ( 1 u / day ) , and insulin lyspro every 6 h. further investigations revealed that there was no evidence of pancreatic exocrine failure .\ntransfontanelar and abdominal ultrasounds ; electroencephalography and brain magnetic resonance imaging showed no relevant findings . an interatrial communication\n ostium secundum , associated with enlargement of right cavities was found in the echocardiogram .\nc - peptide was 0.37 ng / ml ( 0.804.20 ) ; auto antibodies against islet cell ( ica ) , decarboxylase of glutamic acid ( gad ) , and insulin were all negative .\nthe infant was referred to a tertiary hospital due to instability of his metabolic control , alternating episodes of hypoglycemia with hyperglycemia .\ntwo months later , insulin administration was stopped , given that glycemia was always within normal levels with minimal amounts of insulin . at this stage ,\nthe c - peptide was already normal . at the age of 9 months , his growth had declined from p10 to p<1 .\nthe e227k mutation found in our patient is a gain - function mutation that results in both impaired atp sensitivity and higher intrinsic \nthe e227k mutation has been reported in several other patients with tndm but also in a few with pndm reflecting the phenotypic variability of kcnj11 mutations ( table1 ) .\nthe reason why the same mutation causes a relapsing / remitting form of diabetes in some patients whereas in others it produces a permanent diabetes is unclear 15 .\nit was not demonstrated a clear relationship between the clinical phenotype and the magnitude of the impairment of the atp - sensitive potassium ( katp ) channels .\ntndm may result from a reduction in insulin requirements at the time of remission due to changes in beta cell turnover or to compensatory alterations ( at the level of the beta cell , pancreas , or whole body ) , overcoming the lower effectiveness of the atp sensitive potassium channel .\ntherefore , the genetic background of the patient as well as other still unrecognized environmental factors may play an important role in the phenotypic expression of the mutation . on the other hand\n, the apparent clinical variability may result from confounding factors : patients diagnosed during puberty or early adulthood may have had a period of hyperglycemia that was missed during the neonatal period .\nclinical data of patients with heterozygous e227k mutation wks , weeks ; mth , months ; yrs , years ; dka , diabetic ketoacidosis ; mody , maturity - onset diabetes of the young . the e227k may be inherited from affected parents , or occurs as de novo mutation . in our study , the mutation is present in the affected child but also in his asymptomatic mother , suggesting that there was not a complete co - segregation of the mutation with diabetes .\nthis situation has also been described previously ( table1 ) . in the majority of tndm and\npndm cases caused by kcnj11 mutations 3,13 , including e227k mutations 11 , metabolic control was achieved by replacing insulin therapy with sulfonylureas , which are well - known katp channel inhibitors ( table1 ) .\nthis finding supports the idea that if our patient has a relapse of diabetes , he may achieve optimal glycemic control with oral sulfonylurea treatment , strengthening the importance of the molecular diagnosis even if neonatal diabetes remits .\nthe expression of kcnj11 in the central nervous system and skeletal muscle explain the neurological features associated with syndromic forms of pndm , such as developmental delay , muscle weakness , and epilepsy 16,17 .\nhowever , neurological features were also identified in patients with nonsyndromic forms of pndm and tndm who carried kcnj11 mutations as speech delay , autistic spectrum disorder , and learning disability .\nuntil now it is difficult to assure whether these complications are a consequence of the mutation or whether environmental and/or other genetic factors are involved 6 . in the case herein reported , the infant exhibited axial hypotonia and weak suction reflex , that may be caused by the mutation or / and may be due to exposure to hyperglycemia and ketosis during the first days of the child 's life 1,3,18 .\nfurther studies are necessary to clarify the etiology of neurological impairment in tndm patients who carried kcnj11 mutations and to access the effectiveness of su in improving the neurological development . in conclusion\nmolecular diagnosis should be performed in order to identify those patients who may benefit from su therapy .\nfurther investigation is required to understand clinical heterogeneity and the incomplete co - segregation of the kcnj11 mutation with diabetes , and also the molecular mechanisms underlying the biphasic course of tndm .", "answer": "key clinical messageneonatal diabetes is a monogenic form of diabetes . \n herein , we report on a newborn presenting diabetic ketoacidosis at 17 days of life . \n a kcnj11 mutation was identified . in such cases , \n insulin can be replaced by sulfonylurea with a successful metabolic control , as an example of how molecular diagnosis may influence the clinical management of the disorder .", "id": 217} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthough limited in efficacy in many cases , the control methods available today represent a major progress when compared to the lack of any means for the control of these plants one or two decades ago .\ncrops can be protected by resistance , by selective fungicides , by biocontrol agents , and by cultural methods that did not existed before . the current focus in applied\nbreeding is leveraging biotechnological tools to develop more and better markers to allow marker assisted selection with the hope that this will speed up the delivery of improved cultivars to the farmer . to date , however , progress in marker development and delivery of useful markers has been slow in legumes .\nwe are now also facing an accelerated progress in the genomic and biotechnological research , which should soon provide important understanding of some crucial developmental mechanisms in both the parasites and their host plants and will provide candidate genes for resistance to ascochyta blight .\nthe application of ngs technologies will provide a new research framework and molecular tools to be applied in resistance to ascochyta blight in legumes .\nthe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .", "answer": "legume cultivation is strongly hampered by the occurrence of ascochyta blights . \n strategies of control have been developed but only marginal successes achieved . breeding for disease resistance is regarded the most cost efficient method of control . \n significant genetic variation for disease resistance exists in most legume crops with numerous germplasm lines maintained , providing an excellent resource for plant breeders . \n fast and reliable screening methods have been adjusted to fulfill breeding program needs . however \n , the complex inheritance controlled quantitatively by multiple genes , has been difficult to manipulate . \n successful application of biotechnology to ascochyta blight resistance breeding in legume crops will facilitate a good biological knowledge both of the crops pathogen interaction and of the mechanisms underlying resistance . \n the current focus in applied breeding is leveraging biotechnological tools to develop more and better markers to speed up the delivery of improved cultivars to the farmer . to date , however , progress in marker development and delivery of useful markers has been slow in most legumes . \n the limited saturation of the genomic regions bearing putative qtls in legume crops makes difficult to identify the most tightly linked markers and to determine the accurate position of qtls . \n the application of next generation sequencing technologies will contribute to the development of new markers and the identification of candidate genes for ascochyta blight resistance .", "id": 218} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncongenital adrenal hyperplasia ( cah ) is caused by deficiency of 21-hydroxylase in the \n adrenal glands .\ncortisone acetate ( ca ) is used worldwide as an equivalent to hydrocortisone \n ( hc ) , as the glucocorticoid component of substitution therapy for cah .\nhc is identical to cortisol , while ca is \n nearly equivalent to cortisone apart from the presence of an acetate group at the c21 \n position .\ncortisol represents active glucocorticoid , while cortisone is an inactive form . \n the hepatic enzyme 11-hydroxysteroid dehydrogenase \n ( 11-hsd ) type 1 catalyzes the conversion of cortisone to cortisol by \n reducing the keto group at the c11 position to a hydroxyl group\naccordingly , orally \n administered ca must be converted to cortisol by 11-hsd in order to be \n bioactive .\nthe overall bioactivity of ca given orally has been reported to be 80% of that of hc ( 1 ) .\nfurthermore , a patient with 21-hydroxylase deficiency has been reported as \n a poor responder to ca treatment ( 2 ) .\nwe converted 10 \n of our cah patients from ca to hc substitution therapy , compared clinical and laboratory \n findings before and after the change .\nten patients with cah caused by 21-hydroxylase deficiency were studied ( 6 male , 4 female ; \n ages , 4 to 35 yr ) .\nof the 10 patients , 8 were salt \n losers , who required fludrocortisone in addition to glucocorticoids .\nfor all subjects , hc \n was administered instead of ca , initially at 80% of the previous ca dose .\nthe dose of hc \n then was increased or decreased according to circulating concentrations of \n 17-hydroxyprogesterone ( ohp ) and/or adrenocorticotropin ( acth ) .\ntarget concentrations were \n below 10 ng / ml for 17-ohp and below 50 pg / ml for acth .\ndoses of fludrocortisone were not \n changed . to compare required doses of ca and hc ,\nthe ca requirement was calculated as the \n average of the several months preceding the change of drug , while the hc requirement was the \n dose found to provide stable control of cah after several months .\nthese doses were \n calculated as milligrams per square meter of body - surface area . before and after the drug change , we measured concentrations of 17-ohp and acth , as well as \n patients height and weight . the mean observation period after the drug change was 10 mo ( 6 \n to 14 mo ) .\na radioimmunoassay was used to measure 17-ohp , while acth was measured by \n immunoradiometric assay .\ngenomic dna of a patient who responded poorly to treatment with ca was obtained from \n peripheral leukocytes .\nall exons , exon - intron boundary regions and 2.4 kb of the promoter \n region of 11-hsd were amplified by pcr .\nthen the dna sequence was \n determined using an abi prism 310 genetic analyzer . for bone age determination ,\nthe \n tanner - whitehouse 2 rus method according to the japanese standard was used .\nthe mean 17-ohp concentration during treatment of our patients with ca was 48.6 ng / ml . this \n decreased to 10.1 ng / ml when the treatment was changed to hc ( table 1table 1 demographic , pharmacologic , and endocrinologic data for individual \n subjects , fig .\n1 serum concentrations of 17-hydroxyprogesterone ( ohp ) during treatment were \n significantly lowered by changing from cortisone acetate ( ca ) to hydrocortisone ( hc ) . \n\neach data point represents the mean concentration of 17-ohp of an individual during \n treatment with ca or hc . ) .\nthe mean concentration of acth was 198.0 pg / ml during treatment with ca , decreasing \n to 35.1 pg / ml during treatment with hc .\nwe compared the dose of ca preceding the change of \n drug with that of hc after dose adjustment , when disease control was stable .\nthe average \n drug requirement for ca was 33.9 mg / m , while it was 20.3 mg / m for \n hc . the relationship can be expressed as an equation , hc = 0.58 ca , and the coefficient is \n substantially lower than the conventionally reported dose ratio of 0.8 ( 1 ) .\nin addition , \n older patients required more ca per square meter of body - surface than younger patients .\nthe \n relationship between the ca dose shortly before the change of drug and the final hc dose is \n shown in fig .\n. 2 relationship between the dose requirements of cortisone acetate ( ca ) and \n hydrocortisone ( hc ) . the solid regression line can be expressed as : hc = 0.58 \n ca .. no significant change in the obesity index occurred in any subject in association \n with the change of drug . among subjects who already had attained their adult height , all \n male patients ( cases 5 , 8 , and 9 ) showed short stature attributable to precocious puberty . \n in case 5 ,\nfour patients ( cases 1 to 4 ) who had been diagnosed by \n neonatal screening were at a prepubertal age . in cases 1 to 3 , no change of height sd score \n was recognized before or after the drug change .\ncase 4 showed some auxological change \n related to medication , described below . serum concentrations of 17-hydroxyprogesterone ( ohp ) during treatment were \n significantly lowered by changing from cortisone acetate ( ca ) to hydrocortisone ( hc ) . \n\neach data point represents the mean concentration of 17-ohp of an individual during \n treatment with ca or hc . \nrelationship between the dose requirements of cortisone acetate ( ca ) and \n hydrocortisone ( hc ) .\nthe solid regression line can be expressed as : hc = 0.58 \n ca .\ncase 4 : a 10-yr - old boy was found to have an increased concentration of 17-ohp at 6 yr of \n age , and was treated with ca .\nthe ca dose was increased from 20 mg / m at 6 yr to \n 35 mg / m at 8.2 yr . during this period ,\nheight velocity increased , as did height \n sd score ( 0.1 to 0.8 ) . the bone age ( ba ) / chronological age ( ca ) ratio also increased ( 0.9 \n to 1.2 ) .\nafter conversion to hc at 9.4 yr of age , control of disease improved as evidenced \n by a decrease in 17-ohp . at 10.1 yr of age ,\nthe height sd score had decreased to 0.6 , and \n the ba / ca ratio had decreased to 1.1 . the hc requirement was 20.9 mg / m . in case 5 , we performed dna sequence analysis for 11-hsd type 1 because \n treatment with ca had no effect at all .\ncase 5 : a 13 -yr - old boy was referred from another hospital where he had been treated with \n 28 mg / m of hc . in our outpatient clinic , treatment was changed to 36 \n mg / m of ca . soon afterwards 17-ohp\nincreased abruptly to 260 ng / ml from 5.3 \n ng / ml . the plasma level of acth increased to 1038 pg / ml from 8.3 pg / ml . since this patient \n appeared to be a poor responder to ca , 28 mg / m of hc\ninability to respond to ca initially was thought to result from impaired \n low conversion of cortisone to cortisol , because of low activity of 11-hsd \n type 1 . however , dna sequence determination in the gene encoding this enzyme detected no \n changes from the reported normal sequence in any of the six exons , exon - intron boundary \n regions , or the promoter region ( 2.4 kb ) ( 3 ) .\nin 10 patients with 21-hydroxylase deficiency , we changed the glucocorticoid for the \n substitution therapy from ca to hc .\nindices of control of cah such as 17-ohp , and acth \n decreased , indicating improvement . on average , the final requirement for hc based on these \n indicators , was only 0.58 times the previous dose of ca , which was smaller than previously \n reported ( 1 ) .\nwhorwood and warne ( 4 ) determined urinary tetrahydrocortisone ( the ) / \n tetrahydrocortisol ( thf ) ratios for 14 cah patients treated with ca , and found that better \n control of the disease was associated with lower the / thf ratios .\nthe pharmacologic effect of ca depends on conversion of cortisone to cortisol by \n 11-hsd .\nhowever , when we performed gene sequencing in one of our poor ca \n responders , we found no mutation in the 11-hsd gene including the promoter \n region .\n( 2 ) \n similarly reported failure to detect a mutation in the 11-hsd gene .\nup to \n the present , no 11-hsd gene mutation has been detected in poor responders . \n\neven single - nucleotide polymorphism has not been common , apart from the recently reported \n intronic gene polymorphism ( 5 ) .\nas described for case \n 4 , an individual patient s response to ca can vary with age or other factors .\nin addition , \n blood concentrations of cortisone have been reported to be higher than those of cortisol in \n the neonatal period and early infancy ( 6 ) .\naccordingly \n steroid metabolism in young children may differ from that in school - age or older children . \n in our study ,\na poor response \n to ca , therefore , may involve variability of 11-hsd activity rather than \n genetic changes .\njamieson et al . ( 7 ) reported a 36-yr - old woman who had clinical features of hypercortisolemia \n associated with a normal plasma cortisol concentration and an elevated urinary the / thf \n ratio , possibly caused by a defect in hepatic 11-hsd . in another case of 6 \n\nyr old boy with precocious pubarche had an elevated urinary the / thf ratio ( decreased thf / the \n ratio ) attributed to low activity of 11-hsd ( 8) . this enzyme has attracted considerable attention in studies concerning obesity and other \n endocrinological disorders .\nan agonist at the peroxisome proliferator - activated receptor is \n suspected to regulate 11-hsd , decreasing its activity ( 9 ) . among patients with cah , good responders\nhowever , we found no relationship between \n response to ca and obesity . among our subjects who attained adult height ,\nmale patients were shorter than previously \n reported adult patients with cah ( 10 ) .\nour findings provided no definitive \n indication of whether or not hc is superior to ca in achieving a desirable height .\nhowever , \n in one growing child ( case 4 ) , changing the drug from ca to hc decreased the ba / ca ratio . \n\nfinal height in patients treated with hc might prove to be greater than that in patients \n treated with ca .\nas a therapeutic agent , ca shows considerably greater inter- and intra - individual \n variations in efficacy than hc .\nin addition , we found greater difference in pharmacological \n activity between ca and hc than has been previously reported .\nca would seem inadequate for substitution \n therapy not only in patients with cah , but also those with other forms of adrenal \n insufficiency such as adrenal hypoplasia or hypofunction caused by pituitary disorders . \n\ntreatment with hc is recommended for these patients as well . however , since hc has been \n reported to be too bioavailable to maintain cortisol concentrations within physiologic \n limits ( 11 ) , careful evaluation of physiologic \n aspects of hc - based substitution regimens may be needed .", "answer": "although cortisone acetate is approved worldwide as corticosteroid substitution \n therapy in congenital adrenal hyperplasia ( 21-hydroxylase deficiency ) , its effectiveness \n is uncertain since its biologic activity depends on activation by \n 11-hydroxysteroid dehydrogenase ( 11-hsd ) . \n we sought to \n compare the effect of cortisone acetate with that of hydrocortisone . in 10 patients with \n congenital adrenal hyperplasia , \n cortisone acetate was replaced with hydrocortisone in \n substitution therapy . during this change , \n blood concentrations of 17-hydroxy - progesterone , \n adrenocorticotropin ( acth ) , and requirements for each drug were monitored . \n concentrations \n of 17-hydroxyprogesterone decreased ( mean 10.1 vs. 48.6 ng / ml ) , as did those of acth . \n \n cortisone acetate dose requirements averaged 33.9 mg / m2 , while hydrocortisone \n dose requirements averaged only 20.3 mg / m2 . \n in one of the patients resistant to \n cortisone acetate therapy , dna sequences in the coding regions and promoter of the \n 11-hsd gene were analyzed , detecting no genetic abnormalities . \n \n cortisone acetate is inferior to hydrocortisone as substitution therapy in patients with \n congenital adrenal hyperplasia .", "id": 219} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiabetes represents a challenging health issue in the 21st century with a growing incidence estimated to be 381.8 million patients globally in 2013 and high morbidity and mortality rates .\nthough population data are often scarce , the african continent is expected to bear the most important burden of diabetes during the next coming decades [ 13 ] . however\n, a few countries have developed national strategies to contain this coming epidemic . in many cases ,\nlack of data is the major barrier for setting up efficient programs for prevention and management of diabetes in disadvantaged populations . in senegal\n, there is not yet available data on diabetes burden at national level but one recent survey in saint - louis city ( northern region ) reported a prevalence of 10.4% with two - thirds of patients uncontrolled .\nmoreover , marked disparities had been reported between urban and rural regions where lifestyle habits and access to care are different [ 24 ] .\nthe objective of this study was to compare prevalence and risk factors of diabetes in adult populations living in rural and urban areas in senegal .\nwe performed a community - based cross - sectional survey in saint - louis ( northern region of senegal ) .\nall individuals aged 18 years and living in saint - louis for 3 months were eligible to participate in the study .\na two - stage cluster sampling method was used to select a representative sample of adults living in urban and rural areas of saint - louis .\nwe firstly selected 17 localities as clusters ( 9 urban areas and 8 rural areas ) .\nthen , we randomly took a number of households proportional to population size of each locality ( data available from the national agency of statistics and demography ) . from each household a maximum of two participants\nconsidering -error of 0.05 and a power of 80% , the required sample size was 855 individuals and we added a 20% attrition rate to get a sample of 1026 participants . finally , a total of 1056 persons were sampled to enter the study .\ndata were collected on site during house - to - house visits that were conducted between 7 a.m. and 12 p.m. or at the nearest health centre when patients did not live far away from this facility .\na modified version of the who stepwise questionnaire ( http://www.who.int/chp/steps/ ) was pretested and validated before its use to collect data .\nresearchers assisted by medical students , trained nurse practitioners , and community health workers had to fill the data collection form , to document the sociodemographic status ( age , sex , marital status , education , profession , and education ) , personal and family health history ( regarding , particularly , hypertension , diabetes , stroke , and heart and kidney disease ) , and lifestyle ( nutritional habits , physical activity , smoking , and alcohol consumption ) of each participant .\nanthropometric measurements ( weight , height , waist , and hip circumference ) were performed using standard methods and calibrated devices .\nblood pressure was measured twice at five minutes intervals by a semiautomatic sphygmomanometer and the mean of the two readings was calculated .\nif the difference between the readings was greater than 10 mm hg , a third measurement was performed .\nhypertension was defined as a systolic blood pressure of 140 mm hg or more , diastolic blood pressure of 90 mm hg , any prescription of antihypertensive medication in the past two weeks , or any self - reported history of hypertension .\nserum total cholesterol , ldl cholesterol , hdl cholesterol , and triglycerides were measured with colorimetric method .\nfasting blood glucose ( fbg ) was measured with a glucose oxidase method , and serum total cholesterol , hdl cholesterol , and total triglycerides were measured by an enzymatic calorimetric method .\ndiabetes was defined as fbg 126 mg / dl or by prescription of hypoglycemic agents despite fasting plasma glucose or any self - reported history of diabetes .\nphysical inactivity was defined as less than 30 minutes of moderate activity per week or less than 20 minutes of vigorous activity three times per week , or the equivalent .\nstatistical analyses were performed with stata 12.0 ( stata corp , tx , usa ) .\ncomparison of proportions and means were done using pearson 's chi - square test or student 's t - test as appropriated .\nthe age - standardized prevalence rates were calculated with the direct method , using the results of senegalese general population census as the standard ( http://www.ansd.sn/ ) .\nclinical and biochemical parameters associated with diabetes were assessed , in bivariate analysis , comparing the group with diabetes and the group without diabetes using student 's t - test or a chi - square test .\nvariables significantly associated with diabetes were then included in a multivariate logistic regression model with age , gender , and urbanization as forced variable .\nodds ratio ( ors ) with 95% ci and p values of the final model are presented .\na total of 1056 participants were involved in the study with a response rate of 99.1% . but\n21 of them were excluded from the analysis because of incomplete collected data and 1026 individuals were finally analyzed .\nthe crude prevalence of diabetes in our sample was 10.8% ( 95% ci : 6.9%14.2% ) .\nthe age - adjusted prevalence of diabetes was 7.6% ( 95% ci : 5.4%10.5% ) with a difference between men ( 6.0% ) and women ( 9.0% ) .\nthe mean age of diabetic patients was 46.8 13.5 years ( 1876 years ) .\nthe crude prevalence of diabetes in urban and rural settings was , respectively , 12.7% and 6.8% .\nadjusted prevalence of diabetes was higher in urban areas ( 8.1% ) compared to rural areas ( 4.6% ) ( figure 1 ) .\nalso , in both settings , there was an increase in diabetes prevalence with age as shown in figure 2 .\ncomparing cardiovascular risk of people living in urban and in rural settings , we found similarly high prevalence of traditional cardiovascular risk factors such as hypertension , obesity , and physical inactivity contrasting with low proportion of smokers . regarding the disease awareness ,\n43% of patients were diagnosed during the survey , 36% were previously declared diabetic but without any medical follow - up , and 21% were regularly treated by a physician . the presence of diabetes was associated with common risk factors like age , gender , obesity , and familial history of diabetes ( see table 2 ) .\nunivariate analysis showed that age 35 years ( 10% of diabetics versus 5.5% in people aged < 35 years ) , female gender ( 9.0% of diabetics versus 6.0% in males ) , family history of diabetes ( diabetes prevalence of 8.4% versus 5.1% ) , and obesity ( diabetes prevalence of 13.9% versus 8.3% ) were significantly associated with a higher chance to get diabetes .\nconversely , physical activity and daily consumption of 3 fruits / vegetables were associated with lower risk of diabetes in this population ( prevalence differences of 19.5% and 4.4% , resp . ) . after adjustment for age , gender , smoking , familial history , and obesity ,\nthe risk of diabetes was similar in individuals living in urban area compared to those living in rural areas ( they presented a diabetes risk excess of 27% ) .\nonly age > 35 years ( or = 1.63 , 95% ci = [ 1.482.06 ] ) , existence of family history of diabetes ( or = 1.42 , 95% ci = [ 1.123.77 ] ) , and abdominal obesity ( or = 1.17 , 95% ci = [ 1.001.78 ] ) remained significantly associated with diabetes ( see table 3 ) .\nprevalence of diabetes in sub - saharan africa is variable across countries , ethnic groups , and settings considered . reported data from community - based studies range from 2.8% in rural populations in angola to 28.2% found in south african mixed ancestry populations living in urban areas [ 8 , 9 ] .\nepidemiological studies in rural populations are scarcer but they generally show a lower prevalence [ 1012 ] compared to surveys in urban settings [ 1315 ] . in this study ,\nthe prevalence of diabetes in urban areas is quite twice the one in rural areas .\ncomparable prevalence ratios ( urban / rural ) were found in kenya and in democratic republic of congo .\nas already reported in the literature , we found an increasing prevalence with age which is a major risk factor for type 2 diabetes .\nsome studies found higher prevalence in men [ 10 , 11 ] and others reported the contrary [ 9 , 16 ] . in the present study , female gender , absence of school education , and living in urban setting\nwere associated with diabetes at univariate analysis . however , these associations were no longer significant after adjustment for true risk factors that were abdominal obesity , age , and familial history of diabetes . as underlined in many studies , we found a higher prevalence of diabetes in women compared to men and this difference was more striking among rural populations .\nhowever , these rates are better than what was reported in rural tanzanians ( 8.3 to 13.2% ) [ 17 , 18 ] or south africans ( 15.3% ) or in a previous survey in dakar ( capital city ) where 90% of newly diagnosed diabetics were not aware of their disease .\nrecent forecast suggests an alarming increase of diabetes incidence in africa during the next decade in addition to other noncommunicable and infectious diseases . in the us population between 1980 and 2011 ,\nthe crude prevalence of diagnosed diabetes increased from 2.5% to 6.9% while age - adjusted prevalence rose in the same proportions indicating that changes in the population age structure do not explain the epidemic transition .\nthe true explanation of this rising burden of diabetes in both urban and rural africa is probably multifactorial . with life expectancy increase ,\nthe most important part might be driven by lifestyle modifications ( fast urbanization , physical inactivity , and dietary transition ) which promote obesity and insulin resistance but also environmental and genetic factors have not been well explored .\ndata on the changes in the -cell function and insulin resistance in the early stages of the disease process in african populations are scarce .\na few genetic studies performed in small groups from northern and western africa had identified some polymorphism associated with diabetes but epigenetic factors which should play an important role in the disease onset are still unknown [ 2224 ] . other conditions like hiv and sickle cell diseases are also incriminated in the current epidemics of diabetes in africa [ 25 , 26 ] . despite its epidemiological importance of describing diabetes face in senegalese populations\nfirstly , the cross - sectional design is not suitable for inferential analysis about causality or direction of association between diabetes and other cardiovascular risk factors .\nsecondly , incidence of diabetes could not be calculated to estimate the disease potential progression in the population .\nage , familial history of diabetes , and abdominal obesity are the main risk factors identified .\nprevention program targeting both urban and rural populations are urgently needed in african countries in order to reduce the morbidity and mortality due to diabetes .", "answer": "diabetes represents a challenging global health issue in the 21st century . \n data from sub - saharan african populations are scarce and are usually restricted to urban settings . \n the objective of this study was to compare prevalence and risk factors of diabetes in rural and urban areas in senegal . \n methods . in a community - based survey between january and may 2012 , we included 1027 adults aged 18 years living in northern senegal . \n sociodemographic , clinical , and biological data were collected during household visits . \n multivariate logistic regression was performed to identify factors associated with diabetes . results . \n mean age of participants was 48.0 16.9 years and 65.7% were female . \n participants from urban area represented 55.7% . \n the age - standardized prevalence of diabetes was 7.6% ( 6.0% in men versus 9.0% in women ) . \n prevalence of diabetes was higher in urban areas ( 8.1% ) compared to rural areas ( 4.6% ) . \n disease awareness rate was 43% . \n after multivariate analysis , age ( or = 1.63 , p = 0.001 ) , familial history of diabetes ( or = 1.42 , p = 0.001 ) , and abdominal obesity ( or = 1.17 , p = 0.05 ) were associated with diabetes . \n conclusion . \n diabetes is frequent in urban and rural areas in senegal . \n awareness rate is very low among populations . \n age , family history of diabetes , and abdominal obesity are the main risk factors identified .", "id": 220} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nverruciform xanthoma ( vx ) , which has almost similar histologic features , is also a rare lesion usually found on the oral mucosa or the genital area .\nit is presumably associated with the inflammatory response to mucosal damage.1 however , xanthoma and vx of the esophagus are extremely rare . since the first report by remmele and engelsing2 only 13 cases of esophageal xanthoma have been reported,1,2,3,4,5,6,7,8,9 and since the report by herrera - goepfert et al.,10 only four cases of vx of the esophagus have been reported.10,11,12,13 the etiologies of both lesions are not understood .\nwe describe herein a new case , including a review of all reported cases of xanthoma and vx of the esophagus .\na 70-year - old man with an unremarkable medical history was hospitalized with a complaint of epigastric pain .\nserum total cholesterol , triglyceride , high density lipoprotein cholesterol , and low density lipoprotein cholesterol levels were 151 , 215 , 33 , and 102 mg / dl , respectively .\nmultiple shallow gastric ulcers and a duodenal ulcer were detected and suspected to be the cause of the pain .\nbesides the ulcers , in the upper esophagus 20 cm from the incisors , a 3-mm yellowish granular elevated mucosal lesion was found and a biopsy was performed ( fig .\n1 ) . microscopically , large round cells were aggregated in the lamina propria immediately beneath the squamous epithelium .\nthe etiologies are different , as xanthoma is caused by hyperlipidemia and vx arises presumably as a result of an inflammatory response to continuous mucosal damage.1 however , the etiologies of the two lesions arising in the esophagus are not understood .\nthe characteristics of all reported cases of xanthoma and vx of the esophagus are summarized in table 1 .\nfourteen cases of xanthoma and four cases of vx of the esophagus have been reported .\nhowever , some reports loosely stratified vx into esophageal xanthoma , whereas others have excluded it.6,8 in terms of clinical data , both diseases were found predominantly in men than in women : 9 versus 3 in xanthoma and 3 versus 1 in vx .\nthe median age was 59 years ( range , 37 to 74 ) in xanthoma and .\nthe predominant location was the lower esophagus for xanthoma ( lower , 7 ; middle , 2 ; upper , 3 ) , whereas vx was not reported in the lower esophagus ( upper , 2 ; middle , 2 ) .\nthe median size was not different : 3 mm ( range , 2 to 10 ) for xanthoma and 4 mm ( range , 3 to 20 ) for vx .\nthe associated medical conditions were diverse ; however , two patients with malignant tumors were included in each group : hepatocellular carcinoma and ileocecal lymphoma in xanthoma , and gastric cancer and multifocal cancer ( cancer of the glottis , liver , and trachea ) in vx , although there was no definite association .\nvx is characterized by its histologic features , including papillomatosis , acanthosis , and hyperparakeratosis.11 also , the external morphology is verrucoid .\nnevertheless , findings of large round foam cells in the lamina propria under the squamous epithelium are the same as those in xanthoma .\nit is difficult to differentiate between the two lesions on the basis of gross examination when they arise on the esophagus .\nexophytic and verrucoid features seen in vx of the skin were not observed in the esophagus because most of the reported cases were small in size.10,12 considering that xanthoma and vx are nonneoplastic lesions , differentiating between them could be a waste of effort .\nhowever , these lesions have to be grossly distinguished from ectopic sebaceous glands and small subepithelial tumors such as carcinoid and granular cell tumor because most of the reported esophageal xanthomas are yellowish or white mucosal elevated lesions . in terms of microscopic findings , signet ring cell carcinoma , which contains round cells with abundant cytoplasm ,\nwhile signet ring cell carcinoma has an eccentrically located nucleus because of the intracellularly abundant mucin , xanthoma has a centrally located and small nucleus .\npositive immunohistochemical staining for cd68 , which indicates a histiocytic origin , is another characteristic finding of xanthoma.5 moreover , esophageal cancer and ectopic sebaceous glands do not commonly stain with lugol 's solution ; thus , endoscopists need to be aware of these lesions for the differential diagnosis.6,14 with more case reports of esophageal xanthoma and vx of the esophagus , the characteristics of both lesions will be more clearly elucidated .", "answer": "xanthoma is an uncommon nonneoplastic lesion resulting from the accumulation of histiocytes . \n it predominantly shows cutaneous manifestations associated with dyslipidemia . however , xanthoma of the esophagus is extremely rare . to the best of our knowledge , \n only 14 cases have been reported thus far . \n the clinical significance of this lesion has not been established . \n however , this lesion should be distinguished grossly from ectopic sebaceous glands and small subepithelial tumors such as carcinoid and granular cell tumor . moreover , signet ring cell carcinoma , which contains round cells with abundant cytoplasm and has similar histologic features to xanthoma , should be distinguished microscopically .", "id": 221} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nventricular tachycardia or fibrillation ( vt / vf ) in patients with acute myocardial infarction ( ami ) is associated with a poor prognosis.1 ) despite a better prognosis for early vt / vf compared to late vt / vf , early refractory vt / vf is a serious obstacle for the definitive treatment with primary percutaneous coronary intervention ( pci ) .\none of the recent advances in the field of critical care is the extracorporeal life support ( ecls ) system , which is portable , readily applicable and easy to maintain . before its advent ,\npatients with ami complicated by refractory vf / vt before commencing primary pci would rarely survive or recover without ischemic brain damage .\nsuch patients are among those who can derive the most benefit from ecls at present . in fact\n, ecls has well demonstrated its efficacy in treating in - hospital cardiopulmonary arrest and is being used for broader indications then before.2 ) the use of ecls after prolonged cardiopulmonary resuscitation ( cpr ) , a traditional contraindication , is particularly challenging . here , we present two cases of emergency ecls after prolonged cpr for in - hospital cardiac arrest caused by refractory vf in patients with ami waiting for primary pci .\na 55-year old man visited the emergency room due to acute ch - est pain .\nhis vital signs were stable but his electrocardiogram ( ecg ) showed st - elevation in leads ii , iii and avf as well as q waves in leads v 1 and 2 ( fig .\n1 ) . the patient had a history of repeated amis , for which he had received multiple stents in two different hospitals . despite the higher risk of recurrent cardiovascular events , his compliance seemed poor and he was still a heavy smoker .\nhis current medication included triple antiplatelet therapy , a lipid - lowering agent , a beta - blocker , and an angiotensin - converting enzyme inhibitor .\nthe pain - to - door time was about 30 minutes and the pci team was called after diagnosis of an acute inferior wall st - elevation myocardial infarction ( stemi ) . during the stay in the emergency room , the patient suddenly collapsed from vf .\ncpr was initiated and repeated shocks at maximum energy were administered . throughout about 30 minutes of conventional cpr ,\n, we decided to implement ecls ( capiox ebs , terumo , tokyo , japan ) .\nthe right femoral vessels were accessed guided by anatomical landmarks and ecls was finally implemented , about 2 hours from the initiation of cpr . with full support\n, we achieved a flow rate of 4.8 l / min and mean arterial pressure of 70 mm hg , but vf persisted .\nnow the patient could be transferred to the catheterization room to undergo primary pci , without the need for chest compressions for his fibrillating heart . in the catheterization room\n, the left femoral artery accessed also guided by anatomical landmarks and a coronary angiogram ( cag ) was performed .\nthe right cag revealed one stent in the proximal portion that was totally occluded by a thrombus ( fig .\nthe coronary flow was successfully restored after ballooning , about three hours from the onset of chest pain .\nwe implanted a long drug - eluting stent on the previous stent because the residual stenosis after ballooning was more than 80% ( fig .\nwe finished the procedure by installing an intra - aortic balloon pulsation ( iabp ) catheter to assist recovery .\nthe iabp and ecls could be weaned on the third day and the patient was transferred to general ward on the fourth day .\nhe was discharged with chest wall pain , caused by the cpr , and a large hematoma around the ecls cannula insertion site , which had required a transfusion .\nvital signs were stable but his ecg showed st - elevation in leads v 1 - 4 and isolated vpc .\nhe had hypertension , hypercholesterolemia and acquired immunodeficiency syndrome , for which he received regular medications including anti - viral agents .\nthe pain - to - door time was about 60 minutes and primary pci was promptly arranged after diagnosis of an acute anterior wall stemi . during transfer to the catheterization room , one run of non - sustained vt appeared which could be suppressed with intravenous lidocane .\nhowever , during preparation for the procedure in the catheterization room , a sustained vt developed and turned into vf .\nwe immediately called the ecls team and continued cpr . at about 45 minutes of continuous cpr ,\nnormal sinus rhythm spontaneously restored with the implementation of ecls ( capiox ebs , terumo , tokyo , japan ) via the right femoral vessels .\nrestoration of sinus rhythm resulted in a stable patient with a flow rate of 2.5 l / min and mean arterial pressure of 80 mm hg .\nhis right cag showed no significant stenosis , however , the left cag revealed a thrombotic occlusion of proximal left anterior descending coronary artery .\ncoronary flow was successfully restored after ballooning , about two and half hours from the onset of chest pain .\nwe implanted a drug - eluting stent in the culprit lesion with no further complications .\nhe regained full consciousness the same day , in the absence of any neurological deficit .\nthe ecls could be weaned the second day and the patient was transferred to general ward on the third day .\nfinally , he was discharged with no complications except for chest wall pain caused by the cpr .\na 55-year old man visited the emergency room due to acute ch - est pain .\nhis vital signs were stable but his electrocardiogram ( ecg ) showed st - elevation in leads ii , iii and avf as well as q waves in leads v 1 and 2 ( fig .\n1 ) . the patient had a history of repeated amis , for which he had received multiple stents in two different hospitals . despite the higher risk of recurrent cardiovascular events , his compliance seemed poor and he was still a heavy smoker .\nhis current medication included triple antiplatelet therapy , a lipid - lowering agent , a beta - blocker , and an angiotensin - converting enzyme inhibitor .\nthe pain - to - door time was about 30 minutes and the pci team was called after diagnosis of an acute inferior wall st - elevation myocardial infarction ( stemi ) . during the stay in the emergency room , the patient suddenly collapsed from vf .\ncpr was initiated and repeated shocks at maximum energy were administered . throughout about 30 minutes of conventional cpr ,\n, we decided to implement ecls ( capiox ebs , terumo , tokyo , japan ) .\nthe right femoral vessels were accessed guided by anatomical landmarks and ecls was finally implemented , about 2 hours from the initiation of cpr . with full support\n, we achieved a flow rate of 4.8 l / min and mean arterial pressure of 70 mm hg , but vf persisted .\nnow the patient could be transferred to the catheterization room to undergo primary pci , without the need for chest compressions for his fibrillating heart . in the catheterization room\n, the left femoral artery accessed also guided by anatomical landmarks and a coronary angiogram ( cag ) was performed .\nthe right cag revealed one stent in the proximal portion that was totally occluded by a thrombus ( fig .\nthe coronary flow was successfully restored after ballooning , about three hours from the onset of chest pain .\nwe implanted a long drug - eluting stent on the previous stent because the residual stenosis after ballooning was more than 80% ( fig .\nwe finished the procedure by installing an intra - aortic balloon pulsation ( iabp ) catheter to assist recovery .\nthe iabp and ecls could be weaned on the third day and the patient was transferred to general ward on the fourth day .\nhe was discharged with chest wall pain , caused by the cpr , and a large hematoma around the ecls cannula insertion site , which had required a transfusion .\nvital signs were stable but his ecg showed st - elevation in leads v 1 - 4 and isolated vpc .\nhe had hypertension , hypercholesterolemia and acquired immunodeficiency syndrome , for which he received regular medications including anti - viral agents .\nthe pain - to - door time was about 60 minutes and primary pci was promptly arranged after diagnosis of an acute anterior wall stemi . during transfer to the catheterization room ,\none run of non - sustained vt appeared which could be suppressed with intravenous lidocane .\nhowever , during preparation for the procedure in the catheterization room , a sustained vt developed and turned into vf .\nwe immediately called the ecls team and continued cpr . at about 45 minutes of continuous cpr ,\nnormal sinus rhythm spontaneously restored with the implementation of ecls ( capiox ebs , terumo , tokyo , japan ) via the right femoral vessels .\nrestoration of sinus rhythm resulted in a stable patient with a flow rate of 2.5 l / min and mean arterial pressure of 80 mm hg .\nhis right cag showed no significant stenosis , however , the left cag revealed a thrombotic occlusion of proximal left anterior descending coronary artery .\ncoronary flow was successfully restored after ballooning , about two and half hours from the onset of chest pain .\nwe implanted a drug - eluting stent in the culprit lesion with no further complications .\nhe regained full consciousness the same day , in the absence of any neurological deficit .\nthe ecls could be weaned the second day and the patient was transferred to general ward on the third day .\nfinally , he was discharged with no complications except for chest wall pain caused by the cpr .\nprolonged cpr ( > 30 minutes ) or unwitnessed cardiac arrest are poor prognostic markers for the implementation of ecls.3 ) according to rhee et al.4 ) the time to ecls for in - hospital arrest or shock patients was 4323 minutes in failed weaning cases versus 258 minutes in successful weaning cases in korea . with this in mind ,\nalthough the precise impact of cpr duration on predicting survival or neurologic recovery seems to be unclear , our experiences suggest that well organized cpr can protect the major organs , including the brain , for up to 2 hours in witnessed in - hospital cardiac arrest . with advancements in ecls systems , patients with in - hospital arrest\nmore experience with the use of ecls will help define its most appropriate time of deployment . because primary pci ( the treatment of choice for stemi ) is readily available and highly successful in current practice , patients with refractory cardiac arrest are likely candidates for ecls .\nhowever , conclusions from our limited experiences should not be generalized to other causes of cardiac arrest .\naccording to recent epidemiological study , sustained vt / vf occurred in 5.7% of acute stemi patients undergoing primary pci , which mostly happened before the end of cardiac catheterization.1 ) although the frequency of refractory cardiac arrest is not well documented , it is a potential threat in all patients with ami .\nour experience of the past two years suggests refractory vf / vt accounts for about 2.5% of patients with stemi waiting for primary pci ( unpublished data ) .\nthe importance of chest compression during cpr is increasingly emphasized.5 - 8 ) we think the favorable results of our cases are based on the endeavored cpr , conducted with minimal interruption of chest compression .\nalso , the cpr in both cases was fully directed by the same experienced cardiologist . to improve the outcome of ecls ,\nrapid and accurate cannulation of the ecls system is important . in one of our two cases we spent about 90 minutes on ecls implantation , mostly due to difficulty in cannulation of the pulseless vessel without interrupting chest compression\nthis was further complicated by formation of a large hematoma at the cannulation site , requiring a transfusion .\nwe hope our experiences may contribute to improving the prognosis of patients with cardiac arrest .", "answer": "extracorporeal life support ( ecls ) has well demonstrated its efficacy in treating in - hospital cardiac arrest and is being used for broader indications . \n however , ecls after prolonged cardiopulmonary resuscitation ( cpr ) has been traditionally contraindicated and is now challenging . here , we introduce two cases of successful ecls after prolonged cpr , resulting in a immediate and full recovery . both these acute st elevation myocardial infarction patients waiting for primary percutaneous coronary intervention ( pci ) suddenly collapsed due to ventricular fibrillation ( vf ) , which was refractory to conventional treatment . \n after 2 hours of conventional cpr , the ecls had been implemented and primary pci could be performed . \n subsequent to successful revascularization , the vf was stopped with a single electric shock . in our second case , \n normal sinus rhythm was spontaneously restored after ecls implementation , which was completed after 45 minutes of conventional resuscitation . \n both patients made a full neurological recovery on the day of the event and were discharged with only minor complications .", "id": 222} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlaparoscopic supracervical hysterectomy ( lsh ) has continued to represent a favorable alternative to total abdominal hysterectomy ( tah ) for the treatment of benign gynecologic conditions , particularly due to the reduced complication rates , shorter surgery / hospital stay , and prompt resumption of patient daily living activities .\nnevertheless , studies continue to suggest that lsh should not be used as a treatment for benign gynecological conditions , particularly cervical dysplasia .\nthe purpose of this commentary is to address the primary objections against lsh and further illustrate the benefits inherent in this procedure . initially , the primary impetus for removal of the cervix at the time of hysterectomy in patients with benign conditions was to prevent cervical cancer . however , the incidence of cancer in the cervical stump is extremely low and primarily preventable due to latent disease progression , pap smear technology , and hpv screening .\ntherefore , removing this organ solely for the purpose of preventing cervical cancer appears counterintuitive , especially considering that both at - risk patients and the general nonhysterectomized population receive the same recommended screening guidelines . since lsh involves the removal of the uterine section ostensibly related to the specific condition , the operation fixes many gynecologic problems while it conserves the patient 's anatomy and sexual function by retaining the cervix and its mucous - secreting glands .\nfurthermore , the cervix is not typically associated with pelvic pain or bleeding , and thus patients can thereby avoid the common complaints of vaginal dryness and dyspareunia .\nstudies have further indicated that removal of the normal cervix can cause untoward bladder and bowel consequences , including prolapse and urinary incontinence .\nadditionally , prior research has reported that lsh outcomes coincide with favorable rates of prolapse and vaginal cuff dehiscence ( vcd ) .\nin particular , hur et al examined the prevalence of vcd in a large hysterectomy study , indicating that the condition has a significantly following tah compared with lsh .\nrandomized controlled trials and metaanalyses have documented that lsh is associated with a higher incidence of cervical stump complications ( eg , cyclical bleeding and urinary incontinence ) .\nhowever , the cyclical bleeding with lsh is often slight and can be tolerated if the patient receives adequate preoperative counseling . in terms of stress\nurinary incontinence , tah appears to be associated with more favorable outcomes compared with lsh , whereas there were no reported lower urinary tract symptom ( luts ) differences between the 2 procedures .\nwe contend that because vaginal suspension alters the bladder neck angle and reduces postoperative incontinence , when performing lsh , consideration for suspending both the vagina and the cervical stump may significantly mitigate stress urinary incontinence .\nwhile there were no reported differences between tah and lsh regarding the incidence of luts , urinary tract infections , incomplete bladder emptying and voiding complications increased after tah at 1-year follow - up but decreased in the lsh patients . in an earlier surgical study ,\ngimbel et al also reported a much higher incidence of serious adverse events and perioperative blood loss in patients treated with tah compared with those treated with lsh .\nfurthermore , the tah group exhibited more bladder / ureteral injuries , underwent longer operative times .\npatients who present with recurrent cervical dysplasia should consider having their cervix removed if a total hysterectomy is warranted .\nhowever , when a patient initially presents with cervical dysplasia , lsh may be preferable to hysterectomy particularly given the reportedly lower complication rates , reduced surgical time , and earlier recovery .\nthe combination of improved prevention programs , patient adherence to annual screening recommendations , and an informed community appreciation of the virus 's vaccination distribution may further render this issue inconsequential .\nwe suspect that the controversy surrounding the removal of the cervix is partially attributed to both insufficient lsh outcome studies and because many gynecologic surgeons are not formerly trained or experienced with this treatment option .\nwhile we recognize that both the american college of obstetrics and gynecology and a recent cochrane analysis clearly state that tah is more beneficial than lsh in treating benign gynecologic conditions , clinicians should strongly consider the several encouraging lsh findings and emerging studies that continue to substantiate the efficacy of lsh for treating many common benign gynecologic conditions .", "answer": "recent results from metaanalyses and observational studies have suggested that total abdominal hysterectomy ( tah ) is superior to laparoscopic supracervical hysterectomy ( lsh ) for the treatment of benign gynecologic conditions . \n however , because lsh is associated with fewer intraoperative complications , shorter operative time , and preserves patient anatomy and sexual function in comparison with tah , clinicians should reconsider the benefits of lsh .", "id": 223} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmosquitoes were collected from june to september 2003 at the ejido francisco villa , municipality of pesqueria , state of nuevo leon ( 2547n , 10003w ) , with cdc - type light traps baited with dry ice and mechanical aspiration from resting sites on vegetation and in houses .\nthe area is located 40 km northeast of monterrey and consists of mixed suburban housing and agriculture .\naverage annual rainfall in the region is 550 mm ; the mean annual temperature is 28c .\nafter collection , the mosquitoes were placed on dry ice for transport back to the medical entomology laboratory , faculty of biological sciences , autonomous university of nuevo leon , monterrey , where they were separated into pools of 10 insects each , based on species , date , and method of collection ( table 1 ) .\nthe mosquitoes were stored in a mechanical freezer at 70c and later transported on dry ice to the university of texas medical branch ( utmb ) to be processed for virus isolation .\na total of 2,297 mosquitoes , representing 4 genera and 11 species , were tested in 238 pools ( table 1 ) .\nindividual mosquito pools were titrated manually in sterile , ten broeck tissue grinders containing 1.0 ml of phosphate - buffered saline , ph 7.4 , containing 30% fetal bovine serum and antimicrobial agents ( penicillin , streptomycin , and amphotericin ) .\nthe resultant suspension was centrifuged at 12,000 rpm for 5 min ; then 200 l of the supernatant was injected into a flask culture of vero cells .\nafter the solution was absorbed for 1 h at 37c , maintenance medium ( 9 ) was added ; cultures were maintained in an incubator at 37c and examined daily for evidence of viral cytopathic effect ( cpe ) for 14 days . a single pool of cx .\nquinquefasciatus yielded a virus isolate , designated nl-54 , which produced cpe on approximately day 7 .\nthe isolate was identified as wnv by immunofluorescence , hemagglutination - inhibition ( hi ) test , complement - fixation test , vectest wnv / sle antigen assay ( medical analysis systems , camarillo , ca , usa ) , and reverse transcription polymerase chain reaction ( rt - pcr ) ( 9,10 ) .\nthe wnv human isolate was from a 62-year - old mexican woman living in the municipality of etchojoa ( near ciudad obregon ) in sonora state .\nshe visited a local hospital in july 2004 with symptoms of fever , headache , vomiting , arthralgias , and myalgia .\nan acute - phase blood sample was obtained , and a presumptive diagnosis of dengue fever was made .\nthe patient was sent home and subsequently completely recovered . when rt - pcr using dengue primers was negative on the acute - phase serum , a culture was performed .\nwnv was isolated from the sample at the state public health laboratory in sonora and at utmb , upon culture in vero cells .\nhi tests conducted on the acute - phase serum at utmb with west nile , st .\nlouis encephalitis , yellow fever , dengue 1 , and dengue 2 viral antigens were negative , which indicated that the patient had no preexisting flavivirus antibodies .\nan immunoglobulin ( ig ) m enzyme - linked immunosorbent assay ( 11 ) , performed on the acute - phase specimen and a 30-day convalescent - phase serum specimen in sonora , demonstrated seroconversion and the presence of wnv - reactive igm antibodies in the convalescent - phase serum sample .\nviral rna was extracted from the 2 wnv strains after a single vero cell passage directly from 140 l of the infected cell culture supernatants , using the qiaamp viral rna extraction kit ( 12 ) .\nrt - pcr was performed by using 3 primer pairs to amplify the entire prm - e genes of each wnv isolate as previously described ( 12 ) .\npcr products were gel purified with the qiaquick kit ( qiagen , valencia , ca , usa ) according to the manufacturer 's protocol , and the resulting template was directly sequenced with the amplifying primers .\nanalysis and assembly of sequencing data were performed with the vector nti suite software package ( informax , frederick , md , usa ) .\nnucleotide and deduced amino acid sequences of the 2004-nucleotide region representing the prm - e genes from each isolate were aligned with the alignx program in the vector nti suite and compared to sequences of selected north american wnv isolates for which the prm - e genes were available in genbank .\nphylogenetic trees were constructed by bayesian analysis with the program mrbayes , version 2.0 ( 13 ) , with the metropolis - coupled , markov chain , monte carlo algorithm run with 4 chains over 150,000 generations under a general time - reversible model with a burn - in time of 50,000 generations .\nthe bayesian consensus tree was compared to trees generated by neighbor - joining , maximum parsimony , and maximum likelihood analyses using paup , version 4.0b10 ( 14 ) , and each method generated trees with the same overall topology .\nthe consensus phylogram of the 40 wnv isolates generated by bayesian analysis ( 13 ) is shown in the figure , with confidence values at relevant nodes to demonstrate statistical support for each clade . \nphylogram of 2 west nile viruses ( wnv ) isolated from a mosquito pool and human serum in mexico ( shown in bold ) .\nthe phylogenetic tree was generated by bayesian analysis of a 2004-nucleotide region of the prm and e genes of 40 wnv isolates rooted by the most closely related old world strain , israel 1998 .\nay963774 ) , to the prototypical north american wnv isolate , wn - ny99 ( genbank accession no .\nay371271 ) ( 2 ) , and an isolate collected in harris county , texas , in 2002 ( genbank accession no .\nay185906 ) ( 15 ) indicated nucleotide and deduced amino acid differences and similarities among each of the isolates .\nboth the mexican mosquito and human isolates reported herein shared a nucleotide mutation at position 660 ( c to u ) of the prm gene and 2 mutations at positions 1442 ( u to c ) and 2466 ( c to u ) of the e gene .\neach of these 3 mutations was shared with a 2003 horse strain from nuevo leon ( mexnl-03 ) ( 7 ) and a 2002 bird isolate from harris county , texas ( tx-1 ) ( 15 ) .\nthe mutation at nucleotide 1442 also represented a deduced amino acid substitution in the envelope protein ( v159a ) .\nthe mexican mosquito and human isolates reported herein shared a unique mutation at genomic position 1320 ( a to g ) in the e gene .\nthe human isolate also had 3 additional mutations in the e gene at positions 1074 ( g to a ) , 1656 ( u to c ) , and 1974 ( c to u ) .\nthe nucleotide mutations at nucleotide positions 660 , 1442 , and 2466 have also been described in most wnv isolates sequenced from texas , illinois , and colorado in 2002 ( 12 ) .\nthis finding suggests that isolates obtained from northern states of mexico ( i.e. , nuevo leon and sonora ) were derived from wnv strains circulating in the western united states .\nonly a single mutation at position nucleotide 2466 was shared by these 2 isolates and a 2003 bird isolate from tabasco state ( tm171 - 03 ) .\nthis finding supports results from earlier studies that suggest separate introductions of wnv into mexico ( 2,7 ) .\nphylogenetic trees generated by a number of methods indicate that the recent mexican mosquito and human isolates belong to the clade comprised of wnv isolates collected outside the northeastern united states after 2001 , with the exception of isolates collected along the southeast coast of texas .\n( those isolates constitute a separate , sister clade relative to all other north american wnv isolates sequenced to date [ figure ] . ) . because of a shared mutation between the recent mexican mosquito and human isolates ,\nthese 2 virus strains constitute a distinct subclade within the larger us 2002 clade that is supported by strong bayesian confidence values ( 94% ) .\nthe accumulation of 3 additional nucleotide mutations in the 2004 mexican human isolate is illustrated by longer branch lengths in comparison to the 2003 mosquito pool isolate nl-54 , which suggests the continued microevolution of wnv in mexico from year to year .\n* nucleotide numbers correspond to wn - ny99 ; amino acid substitutions are in brackets . genbank accession number . \nour patient represents the first reported autochthonous human case of confirmed wnv infection in mexico .\nthe paucity of human cases reported to date from mexico is curious for several reasons : 1 ) a large number of cases are reported from the united states , 2 ) available evidence indicates that wnv is now widely distributed in mexico ( 17 ) , 3 ) most of the wnv virus strains circulating in the republic are genetically similar to those in the united states ( figure ) .\none explanation for this difference could be the failure of local health personnel to recognize the various clinical forms of wnv infection .\nas illustrated by our patient , west nile fever can easily be mistaken for dengue fever\n. a second reason may be the difficulty of making a serologic diagnosis of wnv infection among persons living in geographic regions where several different flaviviruses circulate , and people have multiple flavivirus infections ( 11 ) .\na third and related possibility is that wnv infection may be less severe in persons with preexisting heterologous flavivirus antibodies ( 11 ) .", "answer": "west nile virus has been isolated for the first time in mexico , from a sick person and from mosquitoes ( culex quinquefasciatus ) . partial sequencing and analysis of the 2 isolates \n indicate that they are genetically similar to other recent isolates from northern mexico and the western united states .", "id": 224} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey may occur at any point and age along the line of the repaired cleft .\nreported recurrence range , after surgical correction of cleft palate , varies between a wide range of 10% and 30% depending on the technique used and age at the time of primary repair .\nsmall fistulas may be asymptomatic but patients commonly complain of regurgitation of liquids into the nose , and food may become impacted with resultant malodor .\npalatal fistulas can be variedly located in reconstructed palate starting from alveolar margin to anterior third , middle third , or posterior one - third of palate .\nthe probable cause for occurrence of anterior palatal fistulas ( apfs ) is anatomically shorter lesser segment , wide palatal cleft defect with thin palatal shelves , improper reflection of subperiosteal flap , and improper closure .\nthis study is a retrospective record review of patients diagnosed with apf in 3.5 years ( which reported in our unit between january 2010 and july 2013 ) .\na total number of 91 patients with anterior palate fistula were operated in this duration .\nthere were forty cases of unilateral apf which were treated with one or another technique surgically depending on various factors influencing the choice of surgical technique .\npatients were categorized in the study depending on the procedure followed for the apf closure .\nanalysis of preoperative , immediate postoperative , and 1-month follow - up pictures was done to check for the site of occurrence , type of cleft , evaluation of adjacent tissue , size of fistula , postoperative healing , and closure with various techniques to compare and evaluate the results and outcome along with complication if any . out of the forty patients included in the study ,\nprimary palate closure of ten patients was done in our unit ( bhagawan mahaveer jain hospital , bengaluru , india ) , whereas thirty were treated elsewhere for repair of cleft palate primarily . in the study ,\nunilateral apfs were evaluated depending on their site of occurrence , type of cleft , evaluation of adjacent tissue , and the size of fistulae .\ndepending on the site of occurrence , apf were categorized into three locations : alveolar fistulae , alveolar fistulae extending to hard palate , and fistulae in hard palate [ figure 1 ] .\n( c ) fistula in hard palate all the palatal fistulas were evaluated for the adjacent tissue in which the quality of tissue was assessed if it is a normal anatomical tissue or secondary mucolized tissue postpalatoplasty .\n( b ) normal anatomical tissue techniques adopted for closure of apf were anterior palate redo with bardach 's principle [ figure 3 ] , closure with rotation of island flap [ figure 4 ] , closure with crevicular flap , closure with buccal advancement flap , and closure with tongue flap and vomer flap . ( a ) unrepaired anterior palatal fistula .\nas shown in table 1 , forty cases were split for surgical correction into various options depending on their size , site , and quality of the tissue .\nmost of the cases were operated with a bardach 's redo for fistula closure ( n = 16 ) ( 40% ) and crevicular flap technique ( n = 13 ) ( 32.5% ) .\nour overall success ( satisfactory results ) was 77.5% as observed in 31 out of 40 cases with individual success rates for bardach 's and crevicular being 75% and 77% , respectively . there was reduction in size of fistula in three cases ( 7.5% ) and a remnant pinpoint hole in four cases ( 10% ) among all the operated cases .\nwe observed just two breakdowns of repair in forty cases . during evaluation of all the three cases managed with vomer flap ,\nresults were considered satisfactory in case of the absence of any symptomatic or asymptomatic fistula , no particular complaints by patient or nasal regurgitation . indicating the split up of 40 cases into various surgical techniques adapted for apf closure and comparison of result\neven today , cleft palate and its associated surgical repair are rated among the greatest challenges in reconstructive surgery . a successful treatment outcome expected after repair of cleft palate includes achieving normal speech without increasing maxillofacial growth disturbances .\nfactors predisposing to development of postoperative dehiscence or fistula include width of the palatal cleft , amount of deficiency of palatal segment , misplacement , and distortion of the cleft segment .\nother extrinsic variables considered for the fistula formation are the timing of repair , sex of the patient , surgical procedures , and the operating surgeon .\nearly dehiscence and fistulas are primarily caused by errors in technique such as inadequate mobilization , closure under tension , injury at reintubation , poor handling of the tissue , failure to achieve a layered closure , and postoperative bleeding and infection .\ndenny and amm proposed closure of palatal fistula with anterior palate redo with bardach 's principle .\nthey documented the technique of total palatal elevation to be a safe and reproducible technique for closure of hard palate fistulas using local palatal flaps .\nthe authors were of the opinion that this technique possesses added advantage of allowing direct visualization of all the elements essential for a successful repair .\nour results held resemblance to this concept since we were able to achieve a successful treatment outcome in 75% of the cases .\nhenderson discussed the use of advancement island flap for the closure of apf and named it as the tadpole flap . \nalthough lesser number of defects were repaired in the current case series with island flap , but almost all of them showed satisfactory healing outcome .\ncarstens in his study put forward the sequential cleft management with sliding sulcus technique and alveolar extension palatoplasty .\nhe stated that conventional methods of cleft lip repair deprive the anterior ( buccolingual ) alveolar mucoperiosteum of blood supply from the facial - internal maxillary arcade .\nafter 6 months , while performing palatoplasty , the lingual incisions permanently isolate the lingual mucoperiosteum from vascular supply which is the greater palatine artery , thereby transforming the osteogenic alveolar mucoperiosteum from a richly supplied boundary zone between the two angiosomes into an isolated tissue surviving primarily on osseous backflow .\nsubperiosteal techniques that preserve the blood supply to this tissue is considered in a sequential plan of cleft management .\nthe authors were able to perform apf repair in 13 cases through this technique in our study with a predictable healing result in 77% cases .\nanother approach utilized by jackson for the management of small- and moderate - sized fistulae involved a combination of buccal and palatal flaps along with bone grafting .\nhowever , such an intervention was performed in fewer number of patients in this study .\nanother attempt made by the surgeons to repair apfs with secondary mucolized tissue involved creating a vomer flap in small figure of three which was associated with significantly improved healing outcome in all the cases .\nperhaps , an exclusive study on fate of vomer flap would provide more precise details regarding the predictability of this technique .\nhenceforth , the authors have made an effort to put forward treatment options for apf depending on their location by means of a simplified algorithm [ figure 5 ] .\nfor an apf , exclusively in alveolus buccal flap or crevicular flap can be used if patients ' age is over 11 years , whereas for patients ' younger than this secondary alveolar bone grafting with or without prior orthodontics or buccal flap appear to be more suitable . during management of fistulas extending to hard palate or into the hard palate , selection of the treatment modality depends on a major extent on the tissue quality . in case of normal palatine tissue ,\nwhereas in cases with secondary mucolised tissue , if it is present over greater segment , a vomer flap is advocated ; if it is bilateral , tongue flap is advised ; and in case of lesser segment , rotation of the greater segment is recommended .\nthe current study was based on a stringent protocol regarding the selection of a surgical treatment plan based on anatomical location of fistula and the quality of surrounding tissue .\npostoperative follow - up of maximum number of cases revealed minimal complication or recurrence rate .\nadditional factors that could be included in future studies for similar clinical cases include speech , etiology of fistula , and width of palate at the time of primary closure .\nfurthermore , we believe that a long - term follow - up of at least 6 months would be better to provide more reliable result", "answer": "aim : aim of this retrospective study was to access the various surgical treatment options available for repair of anterior palatal fistula depending upon their size and presenting age , and also to anticipate the treatment outcome.materials and methods : the series include study report of forty patients with secondary anterior palatal fistula post cleft palate repair , reported in a single unit during a duration of 3 years . \n all the cases were managed surgically under general anesthesia . \n the patients were classified depending upon the location of anterior palatal fistula ( apf ) , the quality of tissue and age of patients to chalk out a justified treatment option outlay.results:forty cases were split for surgical correction into various options depending on their size , site , and quality of the tissue . \n most of the cases were operated with a bardach 's redo for fistula closure ( n = 16 ) ( 40% ) and crevicular flap technique ( n = 13 ) ( 32.5% ) . \n our overall success ( satisfactory results ) was 77.5% as observed in 31 out of 40 cases with individual success rates for bardach 's and crevicular being 75% and 77% , respectively . \n there was reduction in size of fistula in three cases ( 7.5% ) and a remnant pinpoint hole in four cases ( 10% ) among all the operated cases.conclusion:management of post palatoplasty fistulas of the hard palate presents a challenging situation for a clinician following the surgical correction of cleft palate . \n current paper describes the diagnosis and clinical management of forty cases reporting with unilateral apf following cleft palate surgery , over 3 years . \n authors have attempted to propose different treatment modalities for surgical management of unilateral apf . \n it was concluded in the primary review that the size of fistula was irrelevant in determining the clinical outcome . \n instead , the quality and condition of the adjacent tissue appear to be the major governing factors for selecting treatment modality as well as the surgical consequences .", "id": 225} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndyschromatosis is a rare genodermatosis which is characterized by hyper and hypo pigmented macules of variable shape and size .\ncase one was a 30-year - old male patient who presented with asymptomatic multiple hypopigmented , and hyperpigmented skin lesions all over the body [ figure 1a and b ] since the age of 10 years . the initial lesions started in the chest and then spread to the entire body in 2 years .\nthere was no history of photosensitivity or handling of any chemical or any history of drug intake .\nskin biopsy from the hyperpigmented macules showed the increased melanin pigmentation [ figure 2a ] , and the hypopigmented macules showed a marked decrease in the epidermal basal melanin [ figure 2b ] .\nbased on these findings , a diagnosis of dyschromatosis universalis hereditaria ( duh ) was made .\n( a and b ) case one with multiple hypopigmented and hyperpigmented macules all over the body photomicrograph depicting marked increase in the epidermal basal melanin from the hyperpigmented macules ( a ) and decrease in the epidermal basal melanin from the hypopigmented macules ( b ) of all the five cases ( h and e , 400 ) case two was a 22-year - old male presenting to our outpatient department with asymptomatic multiple hypo and hyperpigmented macules all over the body [ figure 3 ] since 12 years .\ncase two with multiple hypopigmented and hyperpigmented macules all over the body case three was a 14-year - old boy who presented with similar lesions all over the body [ figure 4a and b ] since the age of 2 years .\nhe also had multiple verucca vulgaris over the left arm and dorsum of hands [ figure 4c ] .\ncase three with similar reticulate pigmentation all over the body ( a and b ) ; broad nasal bridge , long philtrum ( a ) with verucca vulgaris on the dorsum of right hand ( c ) depicts case three and case four with palms showing similar mottled pigmentation case four was the 9-year - old sibling of the 14-year - old boy who revealed similar lesions all over the body [ figure 6 ] since 9 months of age .\nhe had recurrent pyodermas [ figure 6a ] since birth . on examination , he had molluscum contagiosum lesions [ figure 6b ] on the face . both the siblings also had a broad nasal bridge , long philtrum , and high arched palate . the possibility of primary immunodeficiency was kept and baseline immunodeficiency workup was done .\nhis serum immunoglobulin assay was normal and human immunodeficiency virus one and two tests ( elisa ) were negative .\nboth the brothers had hypopigmented , and hyper pigmented macules of varying sizes all over the body .\ncase four with similar reticulate pigmentation all over the body , abscess over the forehead , molluscum contagiosum ; broad nasal bridge , long philtrum based on these findings , a diagnosis of duh was made in all the four cases .\nthe other differential diagnosis in all these four cases included xeroderma pigmentosum , dyschromatosis symmetrica hereditaria , dyschromic amyloidosis , and disorders due to chemical exposure such as diphenylcyclopropenone , and monobenzyl ether of hydroquinone .\nabsence of photosensitivity , atrophy , telangiectasia , eye involvement and benign nature of the condition makes xeroderma pigmentosum unlikely .\nthese lesions were differentiated from dsh in which the lesions occur in a more acral distribution .\nthe disorder was also differentiated from dyschromic amyloidosis by the absence of predominant lesions in the sun exposed areas and absence of amyloid deposits in the papillary dermis .\ncase five was a 21-year - old male who presented with asymptomatic multiple hypo and hyperpigmented skin lesions over the extremities [ figure 7 ] since the age of 1-year .\nbiopsy from the hypopigmented macules showed decreased melanin pigmentation whereas biopsy from the hyperpigmented macules showed increased focal melanin in the basal layer .\nother possibilities such as duh , and reticulate acropigmentation of kitamura were included in the differentials .\nduh was ruled out as it is characterized by more extensive lesions including the non acral / unexposed areas of the body .\nfurther , the disease is differentiated from reticulate acropigmentation of kitamura by the absence of atrophic macules , palmar pits or breaks in the epidermal ridge pattern .\ncase five with similar lesions over the extremities the features of all these five cases have been summarized in table 1 .\nreticulate pigmentary dermatoses ( rpd ) comprise a rare group of disorders , characterized by hyperpigmented and hypopigmented macules coalescing to form a reticular pattern .\nthe various acral rpd includes reticulate acropigmentation of kitamura , acropigmentation of dohi , acromelanosis heterochromia extremitarium , and dyschromatosis symmetrica hereditaria ( dsh ) .\nthe differential diagnoses of generalized rpd are duh , dermatopathia pigmentoreticularis , naegeli - franceschetti - jadassohn syndrome , and dyskeratosis congenita ( dkc ) .\ndyschromatosis is a spectrum of disease which includes duh , dyschromatosis symmetrica hereditaria ( dsh ) or acropigmentation of dohi and a segmental form called unilateral dermatomal pigmentary dermatosis .\nduh , a rare autosomal dominant genodermatosis was first described by ichikawa and hiraga in 1933 .\nduh is characterized by the presence of both hyperpigmented and hypopigmented , small , irregular macules distributed symmetrically all over the body .\nthese cases usually do not progress or worsen as age advances , once well established .\ntheses macules are usually smaller ( 15 mm ) , but larger macules measuring up to 15 cm have been reported . the trunk and the extremities are commonly involved .\nthe face is generally not involved , and there is sparing of the palms , soles , and mucous membranes .\nvarious systemic associations including small stature and high - tone deafness , dowling - degos disease , x - linked ocular albinism , tuberous sclerosis have been described .\nmany other associated conditions have been reported , such as ocular abnormalities , photosensitivity , learning difficulties , mental retardation , epilepsy , insulin - dependent diabetes mellitus , and erythrocyte , platelet and tryptophan metabolism abnormalities .\nduh is thought to occur secondary to the interference with the neural - melanocytic interaction in early embryonic life in those who are genetically susceptible .\nthe gene responsible for duh has been mapped to 6q24.2-q25.2 ( omim 127500 ) . because the exact biochemical basis of the gene defect is unknown , the diagnosis generally relies on the external phenotype . here\none case was associated with mental and growth retardation , recurrent respiratory tract infection , verucca vulgaris ; and his younger brother had recurrent pyoderma with molluscum contagiosum .\nboth the brothers had characteristic facies of high arched palate , broad nasal root , and long philtrum .\nwe also report one case of dyschromatosis symmetrica hereditaria in a 21-year - old male patient presenting with similar macules over the extremities .\npatients with dyschromatosis symmetrica hereditaria ( reticulate acropigmentation of dohi ) present with hyperpigmented and hypopigmented macules on the face and the dorsal aspects of the extremities .\nskin lesions remain localized on extremities in nearly half of the patients and involve face and extremities in the remaining half .\nmost cases of dsh are inherited as autosomal dominant , although an autosomal recessive variant of dhs has been reported .\nlater , novel mutations in the adra1 were reported in chinese families confirming that this gene is responsible for dsh in the different ethnic group .\nmore recently , suzuki et al . reported 16 novel mutations in the adra1 without identifying such mutations in patients with duh .\nin a recent ultra - structural skin investigation , nuber et al . indicated that duh is a disorder of melanosome synthesis rate or melanocyte activity and not a disorder of melanocyte number .\ndyschromatosis is a benign condition which is usually not associated with systemic involvement which has to be differentiated from conditions like xeroderma pigmentosum , dkc .\nwe report these cases because of their rare occurrence and characteristic facies of high arched palate , broad nasal root , and long philtrum ; recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas as an association of duh has not been reported to the best of our knowledge .\nduh and dsh can present without a family history of similar complaints which has been rarely reportedduh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas . \n \nduh and dsh can present without a family history of similar complaints which has been rarely reported duh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas .\nduh and dsh can present without a family history of similar complaints which has been rarely reportedduh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas . \n \nduh and dsh can present without a family history of similar complaints which has been rarely reported duh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas .\nduh and dsh can present without a family history of similar complaints which has been rarely reportedduh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas . \n \nduh and dsh can present without a family history of similar complaints which has been rarely reported duh can be associated with characteristic facies of high arched palate , broad nasal root and long philtrum , recurrent respiratory tract infections , verucca vulgaris , molluscum contagiosum , and pyodermas .", "answer": "dyschromatosis is a pigmentary genodermatosis which presents with hyper and hypopigmented skin lesions giving a mottled appearance . \n it is a rare entity in india reported mainly in the east asian population . \n classically , two forms have been described ; dyschromatosis universalis hereditaria ( duh ) and dyschromatosis symmetrica hereditaria . here \n we report four cases of duh and one case of dyschromatosis symmetrica hereditaria from india .", "id": 226} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe current research on human diseases primarily focuses on the molecular , microbiological , immunological , and pathological influences .\nthe mechanical basis of disease is now often being explored to decipher any direct contributions toward the physiological response [ 1 , 2 ] . in functionally loaded tissues such as cartilage and bone , cells ( chondrocytes and osteocytes ) experience multiaxial forces ( hydrostatic , compressive , tensile , and shear ) , which play a significant role in modulating the biological function through maintenance of the phenotype and production of a neotissue .\nconversely , abnormal mechanical forces ( either static or dynamic ) can lead to altered cell behavior resulting in pathological matrix synthesis , increased catabolic activity ( degradation ) , and ultimately osteoarthritis or osteoporosis ( apoptosis ) .\nour previous investigations have indicated that chondrocytes and likely other cell types respond to their stress - strain environments in a temporal and spatial manner .\nit has also just been shown that individual cellular mechanical properties may indicate the regenerative potential of mesenchymal stem cells .\ninvestigations of the biomechanics at the cellular level have also identified the biomarkers of disease .\ncytoskeletal stiffness of metastatic cancer cells was reported as more than 70% softer than the benign cells that line the body cavity in patients with suspected lung , breast , and pancreatic cancer .\nthese approaches highlight the utility of single - cell biomechanics as a critical component of advancing microscale therapeutics . \nadvancements in laser technology and microfluidics now allow the use of optical tweezers or traps and fluid mechanics to manipulate isolated single cells [ 8 , 9 ] .\nisolated loads can be applied experimentally to single cells in culture to quantify cellular and cytoskeletal biomechanics .\none can then apply forces and displacements as small as pico - newtons and nanometers , respectively [ 1012 ] .\nthe local microenvironment can therefore be precisely manipulated to facilitate biomechanical test sequences on individual biological cells and molecular structures . in order to explore the connection between external mechanical stimulation and cellular regeneration or degeneration\n, we developed a three - dimensional , multiphysics computational model to fully characterize a unique micromechanical environment .\nthe applied stress state within our custom - fabricated optical and hydrodynamic ( optohydrodynamic ) trap have been mathematically developed from the fundamental equations describing microfluidic creeping flows past a suspended sphere .\nthe objective described in the following paper is to explore the full - field cellular strain response to a range of applied stresses and cellular moduli .\nthe described computational framework will now allow us to develop more realistic cellular models , whose intracellular structures are distinctly identified .\nliving non - adhered , suspended osteoblasts , chondrocytes , fibroblasts , and myoblasts have recently been isolated and mechanically manipulated [ 12 , 16 ] .\nprimary cultures of chondrogenic and osteogenic tissues were generated directly from rat long bones , while muscle cells were acquired from the mouse - derived myoblast c2c12 cell line ( atcc , crl-1772 , manassas , va , usa ) .\nall cells were tested at room temperature experiments ( ~20.5c ) in a flow media consisting of a physiological buffer resulting in a media viscosity of ~1 mpa s. this single cell biomechanical manipulation was made available by combining optical trapping with microfluidics to create the optohydrodynamic trap .\nthis work was facilitated by an instrument , which integrates two laser - based techniques for the mechanical characterization of cellular and biomolecular structures [ 8 , 12 ] . \nthe optical tweezers or the trap component of the device utilizes an infrared laser ( = 1,064 nm ) to suspend micron - sized objects with nanometer position control and pico - newton constraining forces . in the mie regime , where objects are larger in dimension than the wavelength of the trapping laser ( here biological cells ) ,\na ray optics description indicates the transfer of refracted light and the associated momentum into trapping forces ( figure 1 ) .\nmicron - particle image velocimetry can be engaged by incorporating two frequency - doubled lasers ( = 532 nm ) aligned through the same optical path as the ot for full - field flow velocity characterization .\nhowever , the nanoparticles associated with velocity imaging have proven deleterious to cellular health , but provide useful experimental validation of flows around synthetic micron - sized particles\n. the hydrodynamic component of this approach is facilitated through a microfluidic chip design configured in the form of a cross - junction channel ( figure 2 ) .\nthis geometry creates an extensional flow environment and a stagnation point at the channel 's geometric center .\ncells are positioned at the centroid with the optical trap and manipulated with microfluidics , thus creating the optohydrodynamic trap .\nthe cell experiences a total drag force equal to zero , confirmed by integrating the stress tensor as defined by the normal ( form drag ) and shear ( friction drag ) stresses ( figure 3 ) .\nthis reflects the mechanical stability or the saddle - point nature of the optohydrodynamic trap .\nprevious studies describe chip fabrication in detail including the control of the gravity - driven flow initially associated with microfluidic manipulation . \nthe two- and three - dimensional stress states were previously developed as applied to the surface of a nonrotating spheroid cell of radius a , within the optohydrodynamic trap [ 2 , 12 , 14 , 15 ] .\nbriefly , the full - field fluid velocity vector u was constructed from the constitutive equations describing a non - rotating sphere suspended in a general linear flow with viscosity and pressure distribution p . in the polar - spherical components ( r-- magnitudes and er - e-e vectors ) , the generalized flow field produces the individual velocity components : \n ( 1)u = u(ra52(ar)2 + 32(ar)4)sin2cos2er+u(ra(ar)4)sincoscos2e+u(ra(ar)4)sincos2e \n including the pressure distribution \n ( 2)p = p5ua(ar)3sin2cos2. the velocity gradients can be converted into the applied fluid stresses by applying the constitutive equation for an incompressible , newtonian fluid : \n ( 3)t=pi+2e , \n where t is the stress tensor and i is the identity matrix associated with the local isotropic ( hydrostatic ) pressure distribution p. the strain rate tensor e can be characterized by the flow velocity gradient tensor and its transpose : \n ( 4)e=(12)[u+ut ] . by incorporating the velocity and pressure fields into the gradient analysis and then in turn into the constitutive equation ,\nthe fluidic stress tensor can be fully defined as \n ( 5)trr=p+ua(2 + 15(ar)312(ar)5)sin2cos2er , tr=ua(25(ar)3 + 8(ar)5)sincoscos2e,tr=ua(25(ar)3 + 8(ar)5)sinsin2e. defining the stress tensor at the cellular surface , r = a , produces the volumetric fluidic stress state applied to the cell : \n ( 6)tr = ter=rrer+re+re , \n where the full - field stress state can then be defined in terms of distinct normal , rr , and shear , r and r , stress components , respectively , in polar spherical coordinates : \n ( 7)rr=p+5uasin2cos2,r=5uasincoscos2,r=5uasinsin2. \n a three - dimensional presentation of the stresses was developed ( matlab , mathworks , inc . , natick , ma ) for demonstration of the site - specific nature of the stress distributions ( figure 4 ) . \nthe six deviatoric stresses were combined as an effective stress value , eff , as a means to model the three - dimensional stress state : \n ( 8)eff=12[(xy)2+(yz)2+(zx)2 + 6(xy2+yz2+zx2)]1/2 . \n here\n, the maximum polar coordinate derived stresses were converted to the cartesian coordinate stresses such that the maximum normal stresses are located along the x - y - z axes and the maximum shear stresses are defined along the 45 orientation off - axis locations . \nvolumetric strain , e , based on the strain invariants , ii , was defined to encompass the full - field deformation response of the cell within the multiaxial fluidic loading environment and does not apply the small - displacement theory assumption .\nthe cartesian axes associated with the maximum normal strains were determined from a mohr 's circle analysis [ 12 , 20 ] : \n ( 9)e = i1+i2+i3=x+y+z+xy+yz+zx+xyz . the experimental approach described earlier is a planar - wise measurement technique ; thus the optical depth strain value , z , can be determined through a transposition of the planar loading scenario , again through a mohr 's circle analysis : \n ( 10)z=1(x+y ) . \n however , in this modeling presentation here , the full - field stress state and the corresponding strains are fully characterized . \nthe optohydrodynamic deviatoric stress state was applied to an isotropic , homogenous biological cell ( 20 m in diameter ) within a multiphysics computational environment ( comsol v4.0 , palo alto , ca , usa ) in order to determine the individual principal strains and in turn the volumetric strains .\n in this work , we continue to examine the cellular biomechanics induced within a controlled micromechanical environment .\nthree - dimensional cellular strains were computationally modeled in silico with multiphysics software applying the analytically defined stress state ( figure 5 ) .\nvolumetric stress and strain relationships indicated both the nonlinear response of the spherical cellular structure as well as the logarithmic increase in strain with subsequently softer cellular moduli ( figure 6 ) .\nthis relationship is further explored when examining the direct relationship of strain with elastic moduli ( figure 7 ) .\nthe extreme strain response induced in diseased cells indicates their further vulnerability when passively or actively resisting applied stresses .\n we explored the full - field cellular strain response to a range of applied hydrodynamic stresses and cellular moduli , representing various degrees of functional loading and health / disease , respectively .\nthe computational framework now allows us to develop more realistic cellular models with intracellular and membranous structures , distinct in spatial , elastic , and active transport characteristics . \nthe mechanical properties of a single cell are often formulated using either macroscopic or microscopic approaches .\nmacroscopic approaches , as partially described in this work , homogenize every cellular component to produce an isotropic or anisotropic yet homogeneous continuum model so that the mechanical properties of cells can be formulated using temporal and spatially continuous partial differential equations .\nfuture efforts will incorporate a more microscopic approach , which regards the cell as a biocomposite material consisting of randomly or uniformly spaced anisotropic reinforcement cytoskeletal materials within an isotropic medium .\nthe microscopic approach generally obtains the biomechanical response of a single cell by applying the mechanical boundary conditions at the individual fiber and matrix level , scaling up to the cellular level .\nmicroscopic approaches often provide much more detail into the subtle interaction between the cytoskeletal fibers and matrix , which potentially leads to a more accurate model of the cellular behavior , such as characterizing the irreversible deformation of the cellular skeleton .\nunfortunately , refined microscopic models suffer from inhibitory computational and storage costs [ 26 , 27 ] . \nwhen interpreting the potential geometric changes in cellular shape associated with mechanical loading , the cell may experience some interesting membrane transitions triggering unique biologic cues . under suspension and hydrostatic loading , the cell 's volume ( v ) can be defined as a sphere , v = 3/4abc , with radii a = b = c. as seen here during the hydrodynamic extensional loading state , the isotropic , homogenous cell model deformed into a scalene ellipsoid ( a b c ) with equal and opposite tensile and compressive strains in the horizontal plane .\nhowever , with the future inclusion of intracellular structures and organelles as well as nonlinear elastic properties assigned to the membrane and cytoskeleton , cellular models may also deform into either an oblate spheroid ( formed when an ellipse is rotated about its minor axis , a = b > c ) or a prolate spheroid ( formed when an ellipse is rotated about its major axis , a = b < c ) .\nthe resulting shape here replicated a scalene ellipsoid likely due to different maximum stresses applied in the three orthogonal axes .\nongoing experiments and modeling will continue to explore multiaxial single - cell biomechanics as well as the biologic triggers associated with geometric shape - shifting . \nthe described multiphysics computational framework will facilitate more realistic cytoskeletal model interpretations , whose intracellular structures can be distinctly defined , including the cellular membrane substructures , nucleus , and organelles .\nfuture results will provide mathematical outcomes supporting the ongoing investigations in tissue and cellular engineering .", "answer": "controlled external chemomechanical stimuli have been shown to influence cellular and tissue regeneration / degeneration , especially with regards to distinct disease sequelae or health maintenance . \n recently , a unique three - dimensional stress state was mathematically derived to describe the experimental stresses applied to isolated living cells suspended in an optohydrodynamic trap ( optical tweezers combined with microfluidics ) . \n these formulae were previously developed in two and three dimensions from the fundamental equations describing creeping flows past a suspended sphere . \n the objective of the current study is to determine the full - field cellular strain response due to the applied three - dimensional stress environment through a multiphysics computational simulation . in this investigation , \n the multiscale cytoskeletal structures are modeled as homogeneous , isotropic , and linearly elastic . \n the resulting computational biophysics can be directly compared with experimental strain measurements , other modeling interpretations of cellular mechanics including the liquid drop theory , and biokinetic models of biomolecule dynamics . \n the described multiphysics computational framework will facilitate more realistic cytoskeletal model interpretations , whose intracellular structures can be distinctly defined , including the cellular membrane substructures , nucleus , and organelles .", "id": 227} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npapillary and follicular carcinomas of the thyroid gland , commonly referred to together as differentiated thyroid carcinoma ( dtc ) , are characterized by a slowly progressive course , and a 10-year survival rate as high as 80 - 95% .\ndistant metastases are seen in a minority of the patients and the reported rates of occurrence range from 4% to 15% .\nthe most common site of distant metastases is the lung , followed by the bone .\nwe present a case of asymptomatic radioiodine - avid renal and brain metastases presenting 20 years after hemi - thyroidectomy for adenomatous goiter and identified with i - whole body scintigraphy ( wbs ) and i single photon emission computed tomography / computed tomography ( i - spect / ct ) .\na 65-year - old man , investigated at a different hospital for intermittent cough and white - colored expectoration for 4 months , was found to have multiple bilateral nodular lesions on a chest x - ray [ figure 1a ] and a hyperdense lesion ( arrow ) in the right posterior parietal lobe of the brain on ct [ figure 1b ] .\nhe had undergone left hemi - thyroidectomy 20 years previously , reportedly for adenomatous goiter .\nsince serum thyroglobulin ( tg ) was > 3000 ng / ml , a provisional diagnosis of metastatic dtc was made .\nhowever , abdominal ultrasonography ( usg ) showed multiple echogenic round lesions with areas of necrosis and internal vascularity in both kidneys .\n( a ) chest x - ray showing multiple nodular lesions in both lungs and ( b ) computerized tomography of the brain showing a hyperdense lesion ( arrow ) in the right posterior parietal lobe i wbs [ figure 2a ] and spect / ct [ figure 2b and c ] performed 48 h after oral administration of 2 mci i showed tracer uptake in the head , neck ( residual thyroid ) , bilateral hilar lymph nodes , right third and fourth ribs with lytic changes , lung nodules , s1/s2 spinal canal , right femur , acetabulum and humerus , and multiple exophytic renal nodules .\nusg - guided biopsy of a left renal nodule revealed only thyroid follicular cells ( positive for tg immunostaining ) with no pathological evidence of malignancy .\npostoperative investigations after 6 weeks showed tg > 3000 ng / ml , anti - tg 30.1 iu / ml , and thyroid stimulating hormone 14.28 iu / ml .\nhe was treated with 207 mci of i under steroid cover ( prednisolone 40 mg / day ) .\ni whole body scan ( a ) 48 h after administration of 2 mci 131i showing increased tracer uptake at multiple sites in the neck , chest , abdomen , pelvis and right thigh .\na small focus of radioiodine uptake is seen on the right side of the head posteriorly ( arrow ) , adjacent to a known focus of tracer contamination ( arrowhead ) .\nsingle photon emission computed tomography / computed tomography of the neck and chest ; ( b ) localizes tracer uptake to residual thyroid , bilateral hilar lymph nodes , right 3rd and 4 ribs with lytic changes and multiple lung nodules .\nsingle photon emission computed tomography / computed tomography of the abdomen ; ( c ) shows tracer uptake in multiple exophytic renal nodules a fifth - day posttherapy whole body planar and spect / ct scan [ figure 3a and b ] confirmed metastasis in the brain ( arrow ) and other sites seen in the pretherapy scan . after an uneventful hospital stay ,\nhe was discharged on a suppressive dose of thyroxin ( 225 g / day ) .\nwhole body planar ( a ) and single photon emission computed tomography / computed tomography ( b ) scans 5 days after 207 mci 131i showing increased tracer uptake in the brain ( arrow ) , d11 vertebra , sacrum , and right acetabulum , in addition to residual thyroid and lungs\ndistant metastases from dtc may present after a latent period of many years . around 10% of the patients with dtc present with multiple sites of distant metastases other than lung , bone , and lymph nodes ,\n50% of which involve the brain , 25% the liver , and 25% other sites .\nthe reported incidence of renal involvement from a primary thyroid malignancy is very rare , being only about 4.5 - 5.9% , whereas of all secondary metastases to the kidneys from all cancers , thyroid cancer constitutes only about 2.5 - 2.7% . so far ,\nmost of the subjects were female and older than 45 years of age , whereas our patient was an elderly male .\nrenal metastasis usually appears in the setting of multifocal metastases , as in the present case .\nhowever , in our patient , no pathological evidence of malignancy was identified in any of the surgically resected thyroid specimens .\nit is possible that malignancy ( most likely follicular thyroid carcinoma ) might have escaped detection in the left hemi - thyroidectomy specimen 20 years earlier ; a similar case has been reported previously .\napart from a recent onset of cough , our patient was asymptomatic in the presence of renal as well as bone and brain metastases .\nmetastases from dtc may develop several years ( occasionally decades ) after the removal of the primary thyroid malignancy .\nfurthermore , they may remain undetected for a long time if no radioiodine intervention is done .\nsince multiple iodine avid lesions were seen throughout the body on planar scintigraphy , a whole body spect / ct scan was performed for lesion localization .\nthis helped in precisely localizing abnormal radioiodine uptake in the hilar nodes , lung nodules , kidneys , bone , spine , and brain .\n. however , our patient showed radioiodine uptake in the brain metastasis in the presence of radioiodine - avid residual thyroid , renal , and other metastases , which is extremely uncommon .\nmetastases to the brain are observed in only about 1% of the thyroid carcinomas and , in one study , 23% of the brain metastases were discovered only at autopsy .\nthe median interval between the diagnosis of dtc and that of brain metastasis was 6.5 years . however , the actual number of reported cases of brain metastases from thyroid carcinoma remains small , and there has been little evidence of benefit from any specific mode of therapy .\nthe median disease - specific survival from diagnosis of brain metastases was 16.7 months for patients who underwent local excision of one or more brain metastases , compared with 3.4 months for those who did not ( p < 0.05 ) .\nour patient had metastatic involvement in multiple organs , which were not amenable to surgery .\nthe patient 's condition improved symptomatically with absence of any cough during the 2 months following iodine treatment ; he is currently doing well under regular follow - up . to conclude ,\nmetastatic dtc should be suspected in asymptomatic patients with incidentally detected lesions , raised serum tg and history of thyroid lesions .", "answer": "a 65-year - old patient , with a history of left hemi - thyroidectomy for adenomatous goiter 20 years previously , was found to have pulmonary lesions on chest x - ray , a brain lesion on computerized tomography ( ct ) , and elevated serum thyroglobulin ( tg ) . while completion thyroidectomy revealed that no pathological evidence of thyroid malignancy , radioiodine - avid pulmonary , brain , and renal and bone lesions were identified on diagnostic as well as posttherapy whole body planar scintigraphy and single photon emission computed tomography - ct . \n subsequent ultrasonography - guided biopsy of a renal nodule showed thyroid follicular cells . \n this case suggests that metastatic differentiated thyroid carcinoma should be suspected in asymptomatic patients with incidentally detected lesions , raised serum tg , and history of thyroid lesions .", "id": 228} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe epstein barr virus ( ebv ) infects b cells . in most cases , ebv - positive patients develop a severe form of infectious mononucleosis which typically manifests with fever , tonsillopharyngitis , lymphadenopathy and hepatosplenomegaly .\ndeficiencies may be characterized by abnormal activity of lymphocyte function leading to hemophagocytosis and multi - organ failure .\nalthough ebv - associated hlh carries a high mortality rate , quick diagnosis and appropriate treatment can subside the disease .\nwe describe here a patient who developed hepatosplenomegaly and pancytopenia at 2 years of age but achieved automatic recovery .\n, there was a clinical suspicion of ebv - induced hlh and the patient was given the option of treatment with rituximab .\nshe received antibiotic treatment due to fever and chills . during the hospitalization period , the patient recovered and developed hemophagocytosis with pancytopenia as well as sores on the lip .\nthe patient underwent bma and nothing abnormal was found . in spite of treatment , the disease did not subside and she developed fever , abdominal distention and edema in her lower extremities .\nphysical examination showed that the patient had decreased deep - tendon reflexes ( dtr ) and was unable to walk .\nclindamycin , ceftazidime , dexamethasone , ivig ( intravenous immunoglobulin ) and g - csf were administered .\nsince the patient did not achieve full recovery , she was transferred to our center .\nbased on clinical symptoms and lab tests ( table 1 ) , bma was performed once again and the result raised suspicion of ebv - induced secondary hlh .\nrituximab was injected once and the patient developed a blood ebv load of zero within one week . in order to control abnormal stimulation of the immune system ,\nthe patient was investigated for mutations in il-2-inducible t cell kinase ( itk ) and negative test results were received .\n( the patient was negative for mutations in il-2-inducible t cell kinase ( itk ) ) .\nshe is now considered to be an acceptable candidate for transplantation from an hla matched sibling donor . \n \nhlh can be divided into two subgroups : primary or familial hlh and secondary hlh .\nthe primary form is an inflammatory disease which is similar to secondary one on the basis of symptoms .\nprimary hlh usually arises in young children less than one year old ( 70% cases ) ; however , in rare cases it can also occur in adults ( perforin gene mutations have been identified in patients with primary hlh ) .\nfor example , type 2 is caused by mutations in genes 21 - 22 and type 5 is due to mutations in the munc18 - 20 that may be accompanied by hypogammaglobulinemia .\nhypogammaglobulinemia was not confirmed in the patient because it was not possible to check mutation ( the related tests were sent to germany to examine the type 5 disease ) .\nebv may also be accompanied by hypogammaglobulinemia for a certain period secondary hlh is associated with immunologic stimulation caused by malignancies and bacterial or congenital infections .\nthe most common causes of secondary hlh are viral infections by ebv , cmv , prob19 and hiv .\nhowever , it may also be seen in patients with immune system defects . , 4 secondary hlh is a known complication of ebv infection , particularly in patients with x - linked lymphoproliferative disease .\nthe incidence of x - linked lymphoproliferative syndrome is 1 in 1,000,000 male infants . \n \ndiagnostic criteria for hlh disease diagnosis of hlh requires the presence of all 5 major criteria .\nif the patient meets only 4criteria but the clinical suspicion for hlh is high , one should initiate treatment , because delays may be fatal .\nalternative criteria 1 or a combination of 2 and 3 may substitute for 1 major criterion . adapted from henter ji , elinder g , ost a.semin oncol . 1991 ; 18:29 - 33 .\nit means that ebv - infected b cells stimulate cytotoxic t lymphocytes leading to hypercytokinemia and stimulation of histolytic cells .\nmore recently , it has been found that chronic stimulation by ebv may cause chronic hlh in the patient . on the other hand\n, ebv causes stimulation , generation and uncontrolled secretion of t - and nk- cells , as well as generation of il2 , infa and il6 .\nthere is another mechanism by which ebv stimulates membrane protein ( lmp-1 ) in cells .\nsimilar to xlp , lmp-1 may cause acquired immune deficiency , leading to hlh accordingly . \n \ntreatment follows two goals : first , to suppress immune response using ivig , steroid and hlh protocol .\nsecond , to inhibit undesirable influence of immune response and cytokine - stimulated cell activation using immunochemotherapy . in cases with neurological symptoms\nthe level of viral dna which is measured by quantitative pcr may be useful to demonstrate treatment response predicting mortality .\nthe dna level reached zero in our patient . using ivig prior to start of protocol 2004\nit has also been recommended in the treatment of ebv - induced secondary hlh monthly . \n \ndecrease of b cells , which have been contaminated by ebv , actually causes decrease of viruses , as it may be useful for our patient as well .\nfinally , treatment - refractory patients , transplant candidates , patients with familial type of hlh , or recurrent disease undergo chemotherapy for 8 weeks .\npatients who respond favorably to treatment do not undergo transplantation but those who experience relapse and exhibit neurological symptoms are considered for transplantation .\nsevere infection of ebv is not associated with life - threatening condition , but our case study needs urgent treatment . in patients with long - term ebv infection , pancytopenia , coagulopathy and hepatosplenomegaly ,\nbma will be performed and the serum ferritin level will be measured as well . for patients with secondary hlh ,\nrituximab can be used when hlh is associated with ebv to inhibit the immune response .\nthus , the main aim of treatment is to reduce the rate of mortality in patients with hlh .", "answer": "hemophagocytic lymphohistiocytosis ( hlh ) is one of the complications of epstein - barr virus ( ebv ) infection . \n although the patients who have developed hlh following ebv have normal immune system , there are a few patients with ebv - induced immune deficiency who develop hlh as well . here \n , we describe the case of a 10-year - old girl with neurological complications caused by ebv - induced hlh . \n the patient received rituximab , leading to weakening inflammation associated with ebv infection and suppression of disease through quick treatment .", "id": 229} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatient 1 , a 55-year - old man who had received a diagnosis of ankylosing spondylitis 7 \n years previously , was admitted to laikon hosptal , athens , greece , in may 2005 for \n evaluation of encrusted vesicular lesions on the face .\nthe patient had been receiving nonsteroidal antiinflammatory agents \n until 12 months before admission , when his medications were changed to infliximab ( 3 \n mg / kg ) plus methotrexate ( 10 mg weekly ) because of his deteriorating clinical \n condition .\nhe was living in a leishmaniasis - endemic area in athens , had no pets in \n his house , and had no history of recent travel abroad .\nthe central scale was removed \n from one of the lesions , and scrapings from the base of the lesion were stained with \n giemsa stain , which showed intracellular amastigotes with peripheral nuclei and \n rod - shaped kinetoplasts .\nresults of indirect immunoflorescent antibody ( ifa ) testing \n were positive for leishmania parasites ( titer 6,400 ) .\ninfliximab \n and methotrexate therapy was discontinued , and treatment with liposomal amphotericin \n b was started at a dose of 3 mg / kg , for days 1 to 5 , and 2 additional doses ( 3 \n mg / kg ) on days 14 and 21 .\neighteen months later , treatment with etanercept was begun \n due to the patient s severe spondyloarthritis ; 2 years after the new \n anti - tnf treatment , he is well , with no signs or symptoms of leishmaniasis .\npatient 2 , a 71-year - old woman who had giant cell arteritis , was admitted to the \n euroclinic hospital , athens , in may 2005 with a high fever and fatigue .\nthe patient \n had been treated with infliximab ( 0.25 mg / kg ) and variable doses of \n methylprednisolone for the previous 2 years .\nshe was also living in an athens suburb , which is \n leishmaniasis - endemic , and had 4 dogs .\nlaboratory tests showed a high level of \n c - reactive protein ( 163 mg /\n06 mg / l ) , high erythrocyte \n sedimentation rate ( 77 mm / h ) , pancytopenia ( hemoglobin level 12.5 g / dl , leukocyte \n count 3,300/mm , platelet count 122,000/ mm ) , and diffuse \n hyperglobulinemia .\nthe examination of giemsa - stained smears from bone marrow \n aspirate demonstrated abundant leishmania parasites , and ifa was \n marginally positive for leishmania antibodies ( titer 400 ) .\npcr was \n positive for the detection of the leishmania genome in peripheral \n blood .\ninfliximab and methotrexate treatment was discontinued , and treatment with \n intravenous liposomal amphotericin b was started at a dose of 3 mg / kg for 5 days . \n \ntwo days later , the fever subsided , and within the next few days , the patient \n recovered from pancytopenia , while the inflammatory markers showed a gradual \n decrease .\nshe received 2 additional doses of liposomal amphotericin b ( 3 mg / kg ) on \n days 7 and 14 , and by that time , she exhibited no signs or symptoms of visceral \n leishmaniasis .\nwe then searched medline , embase , and current contents databases for all reports on \n leishmaniasis in europe and the mediterranean area among patients with autoimmune \n rheumatic diseases , which are often treated with anti - tnf agents . in our search \n strategy , we used medical subject heading terms and text words , including rheumatoid \n arthritis , juvenile rheumatoid arthritis , still s disease , seronegative \n arthritis , psoriatic arthritis , behet s disease , ankylosing \n spondylitis , reactive arthritis , vasculitis , giant cell arteritis , \n wegener s granulomatosis ( anca [ anti - neutrophil cytoplasmic \n antibody]associated vasculitis ) , panarteritis nodosa , leishmaniasis , \n leishmania , and anti - tnf .\nwe found 13 additional cases of \n leishmaniasis in patients with autoimmune rheumatic diseases ( 214 ) , all published after the introduction of anti - tnf agents in 1998 ( table ) .\nall 15 patients ( including our 2 \n patients ) were treated in the past or at the time of the diagnosis of leishmaniasis \n with > 1 standard immunosuppressive agents , including \n corticosteroids ( 11/14 [ 78.5% ] ) patients for whom treatment details were reported ) , \n methotrexate ( 9/14 [ 64.3% ] ) , cyclosporine ( 3/14 [ 21.4% ] ) , cyclophosphamide ( 3/14 \n [ 21.4% ] ) , azathioprine ( 2/14 [ 14.3 ] ) , and chlorambucil ( 1/14 [ 7.1% ] ) . seven ( 46.6% ) \n patients received an anti - tnf agent along with standard immunosuppressive agents . \n \ntwo of the 15 reported patients had been treated with a recombinant \n interleukin1 receptor antagonist ( anakinra ; amgen inc . ,\nthousand oaks , \n ca , usa ) ( 5,13 ) . in most of the patients ,\nvisceral leishmaniasis developed ( 13 patients , \n 86.6% ) , while cutaneous leishmaniasis developed in 2 patients ( 1 was receiving an \n anti - tnf agent ) .\nall patients were living in leishmaniasis - endemic areas of europe \n ( figure ) . *\nreference ; anca , anti - neutrophil \n cytoplasmic antibody ; na , not applicable . \nall \n biologic treatments had been terminated 6 mo before leishmaniasis \n occurred . reported cases of leishmaniasis in patients with autoimmune rheumatic \n diseases in europe , indicated by stars ( 1 case from israel not shown ) .\ndark \n gray shading , distribution of leishmaniasis ; light gray shading , \n distribution of leishmaniasis vector sandfly .\nthe anti - tnf agents were introduced into clinical practice in 1998 , and the first \n case of leishmaniasis associated with anti - tnf blockade occurred in 2001 ( 4 ) . during the 6-year period ( 19982003 ) ,\na total of 6 reports were \n made of leishmaniasis in patients with rheumatic diseases ; 1 ( 16.6% ) occurred in a \n patient treated with an anti - tnf agent . during the ensuing 5 years \n ( 20042008 )\n, 9 cases of leishmaniasis were reported , 6 ( 66.6% ) in \n patients receiving anti - tnf agents .\nthe median duration of previous immunosuppressive therapy , before the diagnosis of \n leishmaniasis , was 60 months ( range 2360 months ) for all 15 patients \n ( able ) .\nfor the 7 patients who received anti - tnf agents , the median \n duration of anti - tnf treatment was 18 months ( range 960 months ) .\nsix of \n these 7 patients were receiving anti - tnf agents when symptoms and signs of \n leishmaniasis occurred . in 1 patient ( 5 ) , biologic treatments had been discontinued 6 months before the diagnosis of \n leishmaniasis ( table ) . only 1 patient had \n been tested for antibodies against leishmania spp . before \n immunosuppressive therapy was begun , and the results were negative ( 6 ) . therefore , this is the only case with compelling evidence that \n leishmaniasis was a primary infection and not reactivation of a latent \n infection .\nour data suggest that the introduction of tnf blockade into the clinical practice is \n associated with increasing reports of leishmaniasis in patients with autoimmune \n rheumatic diseases who live in leishmaniasis - endemic areas of europe .\nnotably , in \n most reported cases , patients had not received anti - tnf agents but other \n immunosuppressants .\nhowever , all cases of leishmaniasis in patients with autoimmune \n rheumatic diseases were reported after 1998 , the year of introduction of anti - tnf \n agents , and most ( 9/15 ) of the reported leishmaniasis cases occurred during the past \n 5 years ( 20042008 ) , mainly among patients receiving anti - tnf agents ( 6 \n of the 9 patients with leishmaniasis ; 66.6% ) .\nthis increase coincides with the \n increasing use of anti - tnf agents during the same period , as prescription practice \n started changing toward treating patients with lower disease activity ( 15 ) .\nanother indirect piece of evidence that tnf blockade may increase the risk \n for leishmaniasis is that the median duration of previous anti - tnf treatment before \n the diagnosis of leishmaniasis was significantly shorter than the median duration of \n immunosuppressive therapy for all 15 patients ( 18 vs. 60 months ) .\nit is unclear for all cases ( with 1 exception ) presented \n in this article whether leishmaniasis was primary infection or reactivation of \n latent disease .\nwe can not also exclude the possibility that the concomitant , \n long - term use of other immunosuppressants , and not the anti - tnf agents per se , \n played a crucial role in the development of leishmaniasis .\ndifferent prescribing \n patterns of anti - tnf agents might influence the number of cases reported from each \n disease - endemic european country .\nhowever , the small number of reported cases and \n the lack of data on differences in the anti - tnf prescribing policies do not allow \n any conclusions to be reached .\nfinally , due to underreporting , the reported cases \n may underestimate the real incidence of leishmaniasis among patients with autoimmune \n rheumatic diseases .\nprospective studies to estimate the incidence of the disease , the impact of risk \n factors and the need for serologic screening for leishmaniasis before initiation of \n anti - tnf agents or any other immunosuppressive treatment are clearly needed .\nthis is \n particularly important since currently only a few patients with autoimmune rheumatic \n diseases receive anti - tnf agents ( 15 ) .\ntherefore , the use of anti - tnf treatment is likely going to increase , \n possibly causing a parallel increase in opportunistic infections such as \n leishmaniasis .", "answer": "we report 2 cases of leishmaniasis in patients with autoimmune rheumatic diseases \n in greece . to assess trends in leishmaniasis reporting in this patient \n population , we searched the literature for similar reports from europe . \n reports \n increased during 20042008 , especially for patients treated with \n anti tumor necrosis factor agents .", "id": 230} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nparkinson 's disease ( pd ) is a chronic and progressive disorder with an estimated prevalence of 2% in adults over age 60 .\nthe study of disease progression and its determinants is of great importance to improve our understanding of the disease in order to optimize treatment . a wide variety of correlations between different subtypes of the disease and the progression of motor and nonmotor symptoms\nhave been reported . a cohort study with an eight - year follow - up found that axial symptoms ( gait and postural instability ) progress more rapidly than other motor features of pd ( tremor , bradykinesia , and rigidity ) .\nlikewise , a study with a nine - year follow - up reported a greater progression of motor scores in subjects with the following characteristics : male gender , older age at diagnosis , akinetic - rigid subtype , and lower baseline motor score . a slower progression of tremor in comparison to other cardinal features of pd has also been reported . on the other hand ,\nnonmotor progression has been less studied . a study derived from the adagio study population demonstrated an increase of 10% in the movement disorder society unified parkinson 's disease rating scale ( mds - updrs ) part i score , which evaluates nonmotor experiences of daily living ( nm - edl ) , in the placebo group through a nine - month follow - up .\nanother study reported a rate of progression for nm - edl of 0.42 points per year , while progression on the motor experiences of daily living ( m - edl ) was reported to be of 0.8 points per year .\nthe objective of the present study is to describe the change in motor and nonmotor symptoms assessed by the mds - updrs and the nonmotor symptoms scale ( nmss ) in a real - life cohort of subjects with pd after a 21-month follow - up .\nsubjects with pd were recruited from the movement disorders clinic of the national institute of neurology and neurosurgery ( mexico city ) .\ndiagnosis was made according to the uk parkinson 's disease brain bank 's criteria by a movement disorder specialist .\nthe study was submitted and obtained approval from the institutional review board and local ethics committee .\nfull signed consent from all participants was obtained in order to participate in the study .\nlevodopa equivalent daily dose ( ledd ) was also calculated . the spanish version of mds - updrs , the parkinson disease quality of life questionnaire ( pdq-8 ) , and the nmss were applied to all subjects at two different cut - points ( initial evaluation and a follow - up visit at 21 3 months ) .\nthe full 65-item mds - updrs was applied by a neurologist with expertise in movement disorders .\nthe mds - updrs consists of four parts : part i , non - motor experiences of daily living ; part ii , motor experiences of daily living ; part iii , motor examination ; and part iv , motor complications .\nthe pdq-8 is a health status scale covering eight different dimensions of health - related quality of life .\neach item is scored using a likert scale ( never , occasionally , sometimes , and always ) .\nthe nmss is a nine - domain scale for the evaluation of nonmotor symptoms in pd ( cardiovascular , sleep / fatigue , mood / cognition , perceptual problems / hallucinations , attention / memory , gastrointestinal tract , urinary function , sexual function , and miscellaneous ) .\neach domain is assessed in terms of severity ( from 0 : none to 3 : severe ) and frequency ( from 1 : rarely to 4 : very frequent ) in the last month .\nthe score for each domain is obtained by multiplying frequency by severity ; total score is the sum of the nine domains .\ndisease severity was categorized using the recently published triangulation - based cut - offs classification of mds - updrs severity ( part i : mild 010 , moderate 1121 , and severe 22 ; part ii : mild 012 , moderate 1329 , and severe 30 ; part iii : mild 032 , moderate 3358 , and severe 59 ; part iv : mild 04 , moderate 512 , and severe 13 ) .\nquantitative data such as mds - updrs , nmss , and pdq-8 scores were compared using a t - test for related samples .\nordinal data ( use of antiparkinsonian drugs ) were compared using a mcnemar test ; when more than two outcomes were present ( disease severity ) the mcnemar - bowker test was used .\nfifty - three patients concluded the follow - up ( 33 women and 20 men ) . in all cases , loss to follow - up was due to migration out of the city resulting in unavailability to attend the follow - up visit . the mean age at the initial visit for the final sample was 64.1 14.3 years and the mean disease duration was 9.1 5.4 years .\ncomparison of treatment schemes between the initial and follow - up visits is shown in table 1 .\nthe frequencies for each severity group according to the mds - updrs at the initial and follow - up visits are shown in table 2 .\nthe comparison of total scores in the mds - updrs , pdq-8 , and nmss between visits is shown in table 3 .\nno statistically significant difference was found in regard to disease severity according to the mds - updrs part iii between the initial and follow - up visits .\nmost of the patients remained in the mild and moderate disease groups , although there was a slight increase in the mild group as a consequence of clinical improvement in subjects initially classified as moderate severity .\nthe mds - updrs part iii demonstrated a statistically significant decrease of 7.2 2.3 points ( 95% ci , 3.1 to 11.2 , p = 0.001 ) between the initial and follow - up visits . when compared by disease severity , subjects with mild disease had a mean improvement of 5.7 0.1 points ( 95% ci , 3 to 8.4 , p < 0.0001 ) ; subjects with moderate disease also showed improvement although statistical significance was not reached ( 8 3.5 points , 95% ci 4.4 to 20.4 , p = 0.159 ) .\nthe m - edl assessed by mds - updrs part ii did not show any statistically significant change between visits . in regard to motor complications assessed by the mds - updrs part iv , a mean increase of 0.9 0.6 points ( 95% ci , 0.8 to 1.6 , p = 0.015 ) was observed .\nwhen analyzed by severity , subjects with a mild disease worsened by 0.4 0.2 points ( 95% ci , 0.1 to 0.8 , p = 0.017 ) .\nno statistically significant association was found between the mean change in the total mds - updrs score and the predominant motor phenotype ( p = 0.397 ) .\nwhen analyzed independently , no association was found between the different mds - updrs parts and predominant phenotype ( part i p = 0.787 , part ii p = 0.286 , part iii p = 0.578 , and part iv p = 0.994 ) .\nno association was found between motor scores and gender ( p = 0.427 ) or disease duration ( p = 0.941 ) .\nno statistically significant change in nonmotor severity as assessed by the mds - updrs part i was found between visits with most of the patients remaining in the mild severity group .\nmoreover , the nm - edl score did not show a statistically significant change between the initial and follow - up visits even when accounting for severity classification .\nconversely , all nonmotor symptom domains in the nmss scale showed an increase in the mean score , as shown in table 4 .\nan increase of 14.3 11.4 points ( 95% ic , 0.47 to 27.4 , p = 0.043 ) in nmss total score was found between visits . even though there was an increase in the score of all domains , the difference was statistically significant only for the perceptual problems and hallucinations item ( 0.2 0.7 to 0.8 2.1 , p = 0.044 ) . when analyzing by disease severity according to the mds - updrs part i score , no statistically significant increase in nmss total score within groups\nthe mds - updrs part i and nmss total scores showed a high correlation ( r = 0.611 , p = 0.01 ) .\nno statistically significant associations were found between nmss scores and disease duration ( p = 0.677 ) , gender ( p = 0.964 ) , or motor phenotype ( p = 0.427 ) .\nno statistically significant changes were found in quality of life as assessed by the pdq-8 between visits .\npd is a progressive neurodegenerative disease . rates of change in motor and nonmotor symptoms appear to progress differently in a nonlinear fashion with a greater increase in the m - edl in comparison to the nm - edl .\ntraditionally , pd severity is assessed using the hoehn and yahr staging . in this regard ,\nthe mds - updrs severity scale was preferred instead due to the fact that the hoehn and yahr scale relies mainly on the motor state . in order to evaluate the impact of nonmotor symptoms a severity classification accounting for them was needed .\nthe recently published cut - off points for pd severity levels based on the mds - updrs had the advantage of including nonmotor symptoms . in the present study ,\nthe overall improvement of seven points in the mds - updrs part iii can be explained by several factors .\nfirstly , the study was carried out at a referral center and the initial evaluation was actually the first time the patient was seen at the clinic . as a consequence ,\nit should be pointed out that although the ledd increased by 120 mg / d , the actual levodopa daily dose was slightly increased .\nthe latter means that no major levodopa dosage adjustments were performed but also that antiparkinsonian drugs were added as expected .\nfor instance , the use of monoamine oxidase inhibitors and the dopamine agonist ledd was doubled .\nit also should be emphasized that motor evaluations were performed during the on clinical state , in contrast to an off state that could be a better index of the disease natural history . on the other hand ,\nan increase in motor complications such as on time with troublesome dyskinesia and motor fluctuations assessed in the mds - updrs part iv was found .\nmotor complications related to dopaminergic treatment are expected to increase with disease progression despite better motor scores .\ninterestingly , no difference in m - edl ( mds - updrs part ii ) was found between visits despite the improvement in motor scales . moreover , health - related quality of life assessed by the pdq-8 also failed to show any improvement . in regard to the nm - edl ,\nreported a significant worsening of nm - edl scores in the mds - updrs in the placebo group , but no change in treated patients . on the other hand , a statistically significant increase of 14% in the nmss total score was observed . even though every nmss domain had an increase in its score , only the perceptual changes and hallucinations item had a statistically significant difference .\nthat is , all the nonmotor symptoms worsened , but only the cumulative effect and hallucinations reached statistical significance .\na possible explanation may be that the worsening in individual nonmotor symptoms was not clinically significant and as a consequence proper management was not initiated .\nfor instance , use of antidepressants remained the same despite the increase in the mood domain score .\nadditionally , some symptoms like hallucinations can be an adverse effect of dopaminergic replacement therapy , as well as a consequence of disease progression .\nour findings oppose the study of lang et al . , which reported a greater decline in m - edl in comparison to nm - edl based on mds - updrs parts i and ii . this study had a longer follow - up period ( up to 5 years ) and only included subjects with pd in early stages .\nit is possible that discrepancy is the result of a shorter follow - up and the inclusion of subjects with varying degrees of severity .\nmore important is the fact that patients in our study received the best medical treatment in comparison to untreated patients enrolled in a randomized clinical trial setting . as such , our study provides a pragmatic view of the effectiveness of interventions in real - life practice .\nit should be highlighted that mds - updrs part i and nmss total scores had a high correlation coefficient , but the mds - updrs part i failed to show any statistically significant difference .\nreported a strong convergent validity between mds - updrs part i and nmss but also a lack of concordance in patients with a high burden of nonmotor symptoms .\nalthough it is expected that mds - updrs scores correlate with the disease duration , the patients assessed in our study had different pd durations . while this issue affects direct extrapolation , it also gives a more objective overview of daily clinical practice .\nsecondly , patients had different therapeutic schemes at the initial evaluation ; thus final outcomes could be influenced by the optimization of the treatment rather than from disease progression . finally ,\nas mentioned before , all scales were applied during patients ' on clinical state in order .\nthis might not reflect the natural history of the disease and therapeutic effect should be considered . on the other hand , nonmotor symptoms did not change with treatment as much as motor scores . also , nonmotor fluctuations were not assessed . in conclusion , we found a motor improvement during the 21-month follow - up accompanied by an increase in motor complications .\nstudies assessing motor and nonmotor changes over time in different stages of severity are needed .", "answer": "background . \n parkinson 's disease ( pd ) is a chronic and progressive disorder . \n rates of change in motor symptoms have been more studied compared to nonmotor symptoms . \n the objective was to describe these changes in a real - life cohort of subjects with pd . methods . \n a cohort study was carried out from 2011 to 2013 . \n consecutive patients with pd were recruited from a movement disorders clinic . \n mds - updrs , pdq-8 , and nmss were applied to all subjects at an initial evaluation and a subsequent visit ( 21 3 months ) . \n disease severity was categorized using a recent classification of mds - updrs severity \n . results . \n the mds - updrs part iii showed a significant decrease of 7.2 2.31 points ( p = 0.001 ) between evaluations . \n a mean increase of 0.9 0.6 points ( p = 0.015 ) in the mds - updrs part iv was observed . \n an increase of 14.3 11.4 points ( p = 0.043 ) in the nmss total score was found ; when assessed individually , the difference was statistically significant only for the perceptual problems / hallucinations item . \n quality of life remained unchanged . \n conclusion . \n motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization . \n nonmotor symptoms worsened as a whole . \n the overall effect in the quality of life was negligible .", "id": 231} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients with heart failure ( hf ) older than 65 years have a two - fold increased risk of cognitive impairment than elders without hf ( 1 ) .\nthe prevalence of cognitive impairment in adults with chronic heart failure is recognized as a factor contributing to the complexity of care for these patients ( 2 ) .\ncognitive impairment may impact the ability to perform heart failure self - care procedures and is associated with an increased risk of re - hospitalization and mortality ( 3 ) . despite the prevalence of these two conditions , cognitive impairment in hf patients\nis usually underestimated by physicians ( 4 ) and currently , there is insufficient evidence to develop recommendations for strategies to improve cognitive impairment for hf patients ( 5 ) .\nthis study was designed to determine factors related to cognitive impairment among elder with hf .\nin this descriptive , correlational , cross - sectional study , 184 patients with chronic heart failure were selected from four mazandaran university of medical sciences teaching hospitals using convenience sampling : imam khomeini hospital in behshahr , fatemeh zahra heart center in sari , imam khomeini hospital in fereydunkenar and imam khomeini hospital in noor .\npatients hospitalized for symptomatic heart failure between october 2013 and january 2014 were included in this study and confirmed by the cardiologists .\ninclusion criteria were a history of at least six months involvement with heart failure , age 60 , and remaining stable 1 - 2 days after admission .\nexclusion criteria were communication problems such as severe hearing impairment ( without hearing aids ) , speech problems , severe cognitive impairment with abbreviated mental test ( amt ) scores < 4 ( 6 ) and uncooperativeness .\nafter providing written informed consent , each patient was interviewed by an independent data collector who was not involved in the patient s care .\nsocio - demographic variables consisted of age , gender , location , living status , education level , and income .\nclinical variables consisted of left ventricular ejection fraction ( ef ) , poly - pharmacy ( 5 different drugs ) , comorbidities ( charlson comorbidity index ) , blood pressure , depressive symptoms , body mass index ( bmi ) , number of hospitalizations during the previous six months , and some biochemical characteristics of the blood . these variables were collected from patients medical records and by interviews .\ncognitive status was measured using the iranian version of the abbreviated mental test . the ideal cut - off point reported 6 , while sensitivity and specificity identified at 88 and 99% , respectively ( 6 ) , using a 10-item scale .\neach correct answer received a score of 1 and incorrect answers were scored as 0 .\na total score of 6 indicates the presence of cognitive impairment ( a score of 0 - 3 indicates severe cognitive impairment and 4 - 6 indicates moderate cognitive impairment ) .\nthe severity of comorbid conditions was assessed using the charlson comorbidity index ( 7 ) , which classifies comorbidities based on the number and seriousness of one - year survival , with higher scores indicating greater risk of death .\nmost diseases are assigned a score of 1 on the index , but more severe conditions are given a weight score of 2 , 3 or 6 .\nfisher s exact test and logistic regression were used to compare cognitive status scores with demographic characteristics and disease related variables .\nthe independent samples t - test was used to compare biochemical characteristics of the blood from the subjects both with and without cognitive impairment .\nsocio - demographic variables consisted of age , gender , location , living status , education level , and income .\nclinical variables consisted of left ventricular ejection fraction ( ef ) , poly - pharmacy ( 5 different drugs ) , comorbidities ( charlson comorbidity index ) , blood pressure , depressive symptoms , body mass index ( bmi ) , number of hospitalizations during the previous six months , and some biochemical characteristics of the blood . these variables were collected from patients medical records and by interviews .\ncognitive status was measured using the iranian version of the abbreviated mental test . the ideal cut - off point reported 6 , while sensitivity and specificity identified at 88 and 99% , respectively ( 6 ) , using a 10-item scale .\neach correct answer received a score of 1 and incorrect answers were scored as 0 .\na total score of 6 indicates the presence of cognitive impairment ( a score of 0 - 3 indicates severe cognitive impairment and 4 - 6 indicates moderate cognitive impairment ) .\nthe severity of comorbid conditions was assessed using the charlson comorbidity index ( 7 ) , which classifies comorbidities based on the number and seriousness of one - year survival , with higher scores indicating greater risk of death .\nmost diseases are assigned a score of 1 on the index , but more severe conditions are given a weight score of 2 , 3 or 6 .\ntest and logistic regression were used to compare cognitive status scores with demographic characteristics and disease related variables .\nthe independent samples t - test was used to compare biochemical characteristics of the blood from the subjects both with and without cognitive impairment .\nthe amt mean was 6.18 2.002 ( minimum 4 and maximum 10 ) , with 95% ci ( 5.89 to 6.48 ) . the majority of the elders in the study ( 110 persons , 59.8% ) had scores of 4 - 6 and the others ( 74 persons , 40.2% ) had scores of 7 - 10 .\nfemales made up 61.4% of participants ( 113 persons ) and 38.6% ( 71 persons ) were male .\nthe 60 - 75 age group comprised 70% of the subjects ( 128 persons ) , 29% ( 54 persons ) were in the 75 - 90 age group and 1% ( 2 persons ) were in the 90 - 94 age group .\nthe mean ages in women and men were 70.7 8.35 and 70.01 8.99 , respectively ( p = 0.595 ) .\nthe ci odds ratio was higher in older patients than in the younger ones ( p = 0.002 ) .\nin addition , the ci odds ratio was higher in female subjects than male ( p < 0.001 ) ( table 1 )\n. there were significant relationships between cognition status scores and living status ( p < 0.001 ) and also between cognition status scores and education level ( p < 0.001 ) ( table 2 ) .\nvalues are expressed as mean sd . the ci odds ratios were higher in subjects with an ejection fraction of < 40% compared to subjects with an ejection fraction of 40% ( p = 0.002 ) ( table 1 ) .\nfisher s exact test results showed a significant relationship between cognitive status scores and hypertension ( p = 0.039 ) and also between cognitive status scores and anemia ( p = 0.046 ) .\nalthough the ci odds ratio was higher among subjects with hypertension and anemia , there was not a significant relationship ( table 1 ) .\nthere was no significant correlation between biochemical characteristics of the blood and cognitive status scores .\nhowever , there was a near - significant level for hemoglobin , blood urea nitrogen ( bun ) and systolic blood pressure ( table 3 ) .\nvalues are expressed as mean sd . the mean of charlson comorbidity index and depression symptoms were higher among subjects with cognition impairment ( p < 0.001 ) ( table 4 ) .\nthe amt mean was 6.18 2.002 ( minimum 4 and maximum 10 ) , with 95% ci ( 5.89 to 6.48 ) . the majority of the elders in the study ( 110 persons , 59.8% ) had scores of 4 - 6 and the others ( 74 persons , 40.2% ) had scores of 7 - 10 .\nfemales made up 61.4% of participants ( 113 persons ) and 38.6% ( 71 persons ) were male .\nthe 60 - 75 age group comprised 70% of the subjects ( 128 persons ) , 29% ( 54 persons ) were in the 75 - 90 age group and 1% ( 2 persons ) were in the 90 - 94 age group .\nthe mean ages in women and men were 70.7 8.35 and 70.01 8.99 , respectively ( p = 0.595 ) .\nthe ci odds ratio was higher in older patients than in the younger ones ( p = 0.002 ) .\nin addition , the ci odds ratio was higher in female subjects than male ( p < 0.001 ) ( table 1 ) .\nthere were significant relationships between cognition status scores and living status ( p < 0.001 ) and also between cognition status scores and education level ( p < 0.001 ) ( table 2 ) .\nthe ci odds ratios were higher in subjects with an ejection fraction of < 40% compared to subjects with an ejection fraction of 40% ( p = 0.002 ) ( table 1 ) .\nfisher s exact test results showed a significant relationship between cognitive status scores and hypertension ( p = 0.039 ) and also between cognitive status scores and anemia ( p = 0.046 ) .\nalthough the ci odds ratio was higher among subjects with hypertension and anemia , there was not a significant relationship ( table 1 ) .\nthere was no significant correlation between biochemical characteristics of the blood and cognitive status scores .\nhowever , there was a near - significant level for hemoglobin , blood urea nitrogen ( bun ) and systolic blood pressure ( table 3 ) .\nvalues are expressed as mean sd . the mean of charlson comorbidity index and depression symptoms were higher among subjects with cognition impairment ( p < 0.001 ) ( table 4 ) .\nin this study , the prevalence of cognitive impairment was higher among elderly subjects with a lower level of education , patients living alone or with their children , and females .\nit seems that fewer years of education contribute to processing speed ( 2 ) . providing social support another important factor that may decrease patient stress and improve cognitive status .\nthe results of the present study show that comorbidities contribute to cognitive impairment in hf patients .\nthese findings are consistent with other studies ( 2 , 9 , 10 ) , but differ from that of pressler et al . who found no association between comorbidities and cognitive status ( 11 ) .\nin this study , there were significant relationships between cognitive impairment with depression , hypertension , and anemia .\nthese findings are consistent with some studies ( 9 , 10 ) . in a clinical setting , it is hard to differentiate mild stages of dementia and late life depression , because both situations may have similar presentations ( 12 ) .\nfew studies have directly examined the association between cognitive impairment and depression in persons with heart failure , despite the likelihood of common mechanisms ( 13 ) .\npersons with heart failure exhibit numerous pathological changes on neuro - imaging , including greater atrophy and the presence of white matter hyper - intensities , frequently in frontal brain regions ( 14 ) .\nhypertension has a significant impact on cardiovascular function , cerebral structural integrity and associated cognitive deterioration ( 15 , 16 ) .\nthe most common explanation for the deleterious effect of hypertension on cognition is that hypertension increases cerebrovascular disease ( 17 ) .\nsome longitudinal studies have shown a positive association between hypertension and cognitive impairment ( 15 , 16 ) .\nthese effects were independent of clinical strokes and the association was stronger in individuals who did not use antihypertensive drugs ( 15 ) .\nthe results of some studies indicate that hypertension may be a risk factor dementia , especially alzheimer s disease ( ad ) ( 18 , 19 )\n. however , the factors that predispose individuals with hypertension to developed ad are unknown ( 20 ) .\nthere have been very few studies on the association of anemia with cognitive status ( 22 ) .\nthe literature on the association between anemia and dementia is also limited and the results are inconsistent ( 23 , 24 ) .\nanemia in heart failure may have multiple origins , which are thought to involve reduced erythrocyte production , decreased bmi , and hemodilution ( 25 ) .\nfurther contributors to the risk of anemia in hf are comorbid renal disease and increased inflammation ( 26 ) .\nelevated levels of pro - inflammatory cytokines may also inhibit hematopoietic proliferation ( 27 ) .\nin addition , some medications , such as angiotensin - converting enzyme ( ace ) inhibitors and angiotensin receptor blockers , reduce erythropoietin production ( 25 ) .\nfirst , this is a cross - sectional study and the correlations can not imply causation relationships between parameters .\nmoreover , the data represent only the subjects who agreed to participate in the study . identifying factors affecting cognitive impairment in hf may help clinicians in directing educational interventions on disease management to families to possibly prevent readmission of their loved ones .\nfurther research to determine the feasibility and acceptability of cognitive assessment in routine clinical care is suggested .\nfirst , this is a cross - sectional study and the correlations can not imply causation relationships between parameters .\nmoreover , the data represent only the subjects who agreed to participate in the study .\nidentifying factors affecting cognitive impairment in hf may help clinicians in directing educational interventions on disease management to families to possibly prevent readmission of their loved ones .\nfurther research to determine the feasibility and acceptability of cognitive assessment in routine clinical care is suggested .", "answer": "backgroundpatients with heart failure ( hf ) older than 65 years have a two - fold increased risk of cognitive impairment than elders without hf . \n identifying factors affecting cognitive impairment in hf may present targets for intervention.objectivesthe aim of the present study was to determine cognitive function and related factors among elderly patients with heart failure.patients and methodsin this cross - sectional study , 184 elderly patients with heart failure were selected from four mazandaran university of medical sciences teaching hospitals using convenience sampling . \n data were collected from patients medical records and by interview , using the abbreviated mental test , geriatric depression scale , and charlson comorbidity index.resultsthere were significant relationships between cognitive status and living arrangement ( p < 0.001 ) , education ( p < 0.001 ) , hypertension ( p = 0.039 ) , anemia ( p = 0.046 ) , charlson comorbidity index ( p < 0.001 ) and geriatric depression scale ( p < \n 0.001).conclusionsscreening of cognitive impairment in elderly patients with heart failure seems necessary .", "id": 232} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n\t\t\t\t olfactory neuroblastoma ( onb ) is a rare malignant tumor arising from the olfactory epithelium of the nasal cavity and the paranasal sinuses .\nthe anatomic origin in the superior nasal cavity leads to nonspecific symptoms that make early diagnosis difficult .\ndirect extension of the tumor into the anterior cranial fossa , either at presentation or at disease recurrence , is common .\nonb is mostly a locally aggressive tumor that can spread to lymph nodes but metastatic involvement of bone , bone marrow , and other organs was also reported .\nthe most commonly used staging system proposed by kadish is currently based on computer tomography and magnetic resonance imaging . in stage\na , the tumor is limited to the nasal cavity , in stage b the tumor extends to paranasal sinus , and in stage c the tumor is extending over the nasal cavity and sinus and/or metastasized distantly .\na histological grading system based on microscopic findings proposed by hyams at 1988 showed a clear correlation of survival with histological differentiation of disease . \nhowever most authors believe that craniofacial resection followed by rt offers the gold standard treatment in this disease . despite aggressive therapies , local , regional relapse , and distant metastasis occur frequently and often after extended periods of follow - up .\ndata for this case series were acquired retrospectively from the files of division of medical oncology , cerrahpasa medical faculty , istanbul university .\nadditional information regarding the clinical course and outcome was collected from the patients ' charts and phone calls to the patients , their relatives , and their general practitioners . in this study , we have reviewed 19 cases of olfactory neuroblastomas treated over 24-year period and analyzed the clinical features , treatment outcomes , and prognostic factors .\nthe data of nineteen patients of olfactory neuroblastomas treated and followed up between 1986 and 2010 at division of medical oncology , cerrahpasa medical faculty , istanbul university , were analyzed retrospectively .\npatient characteristics , initial symptoms , tumor extent , histologic features , primary therapy , tumor recurrence , and treatments of recurrent disease were determined .\npatients were staged according to the kadish staging system . a single pathologist with expertise in head and neck neoplasms reviewed the histological specimens .\nlocal ethics committee 's approval and patients ' or their next of kin 's informed consent were taken before the study .\ntreatment response was assessed by clinical examinations and computed tomography ( ct ) or magnetic resonance imaging ( mri ) .\nsurvival rates were calculated from diagnosis to the death of the patient using the kaplan - meier life table method .\nthe madian age at diagnosis was 46 ( range : 19 to 68 years ) .\ntumor staging was kadish stage a in 3 , stage b in 5 , and stage c in 11 patients .\nfour patients had metastasis of cervical lymph nodes , two brains , one bone marrow , one bone and lung metastases , and one bone , mediastinal lymph node , and liver metastases at the time of diagnosis .\ntumor localization , clinical symptoms , and presentations at the time of diagnosis are listed in table 1 .\nmedian time from onset of first symptoms until diagnosis was 8.8 months ( range : 1.829 months ) .\nthe common presenting symptoms were nasal obstruction ( 53% ) , epistaxis ( 31% ) , rhinorrhea , and facial pain ( 26% ) .\npatient treatments consisted of surgical resection , radiation therapy , and chemotherapy ( ctx ) ( table 3 ) .\ninitial treatments included surgery alone in three patients , radiotherapy ( rt ) with or without ctx in five , surgery plus postoperative rt in seven and multimodality therapy ( surgery plus postoperative ctx plus postoperative rt ) in three , and finally ctx alone in one . in 14 patients ,\nfour of these patients had also radical neck dissection due to cervical lymph nodes involvement .\nnasal tumor resection in 2 patients , maxillectomy plus orbital exenteration in 1 , and external ethmoidectomy ( ee ) in 1 were also used as surgical treatments . of these 14 patients who underwent surgical tumor resection ,\n4 were treated with surgery alone , 5 with adjuvant radiation therapy after surgery , 2 with adjuvant ctx after surgery , and the remaining 3 with radiation therapy and ctx after surgery . of the remaining 5 patients , four in advanced stage and one in early stage refused surgical treatment .\nradiation therapy was administered to two of the patients , radiation therapy followed by ctx to the other two , and ctx alone to one patient .\nthe average radiation dose was 57.9 gy and the ctx was chosen from cisplatin - based regimens . as a part of the primary treatment modality , 12 patients underwent radiation therapy , so did the five relapsed patients .\nas a part of primary treatment modality 8 patients received ctx , so did the three relapsed patients . \nfifteen patients died of tumor progression during the follow - up , of whom 9 were at an advanced stage ( stage c ) by the time of diagnosis and 6 at an early stage ( stage a / b ) .\nkadish stage c patients had a significantly poorer outcome compared to the stage a / b patients ( 2-year survival rate : 71 versus 25% , resp .\nhistopathologically high - grade patients ( grade 3/4 ) had a significantly poorer outcome when compared to the lower grade ( grade 1/2 ) patients ( 2-year survival rate : 16 versus 50% , resp .\nprimary tumor extensions to orbital area had a significantly poorer outcome compared to the tumors with no extension to orbital area ( 2-year survival rate : 22 versus 60% , resp .\nthere was no statistically significant difference in survival rate between male and female patients ( 2-year survival rate : 40 versus 44% , resp .\npatients with age < 45 years had no poorer outcome compared to patients with age > 45 years ( 2-year survival rate : 41 versus 43% ; p = .059 ) .\nbrain and bone marrow involvements showed poorer outcome compared to those without such involvement ( median survival rate : 9.1 versus 28.8 months , resp . ;\nsurvival rate was not significantly different among pateints of kadish c when stratified according to initial treatment ( p = .8 ) . \nlocoregional recurrence developed in 6 and distant metastasis in 6 patients . during the follow - up period , these groups exhibited distant metastasis to the brain , spinal cord , bone , bone marrow , meninges , and lungs .\nas a treatment for recurrence and metastasis , reoperation of primary site plus radiation therapy in 4 patients and radiation therapy alone in 4 patients were offered .\nonb is a rare malignant tumor that comprises 4,65% of malignant nasal and paranasal tumors .\nsome 1000 cases have been reported in the english literature since it was first introduced in 1924 .\nthe incidence rate is bimodal , with peaks in the second and third decades of life and in the sixth and seventh decades of life and equal among females and males . as for our study ,\nthe age at diagnosis was most common in the fourth decade and female - to - male ratio was equal .\nthe average time between the appearance of the first symptom and the diagnosis was reported as 6 months and this period was similar also in our group .\nthe most common symptoms at the initial diagnosis were defined as unilateral nasal obstruction and epistaxis in the literature .\nthis tumor may be misdiagnosed as an undifferentiated small cell carcinoma , melanoma , rhabdomyosarcoma , or other small blue cell neoplasms .\nhyam proposed a grading system with grades 14 based on the presence or absence of seven different histopathological parameters .\nthese are growth , architecture , mitotic activity , necrosis , nuclear pleomorphism , rosette formation , and fibrillary stroma . \n. staining paterns for neuron - spesific enolase , chromogranin , synaptophysin , s-100 , and epithelial markers can be helpful . \nthere is evidence that histological grade of onb influences biologic behavior , particularly because it relates to disease progression , local recurrence , and metastasis . for the well - differentiated tumors a slower disease progression and less tendency for local recurrence have been described . in our study , the 2-year survival rate of this grade i / ii - iii / iv disease was 16 versus 50% , respectively .\nmore aggressive treatment , such as surgery , radiation , and intensive ctx , may be useful for patients with grade iii / iv disease .\na meta - analysis showed that the median overall survival at 5 years is 45% in 390 patients .\nthe distribution of onb from 21 studies according to kadish staging system was 12% at stage a , 27% at stage b , and 61% at stage c. the mean 5-year survival is 75% for stage a , 68% for stage b , and 41% for stage c .\nthe conclusions of the university of virginia stated that kadish stage is predictive of disease - related mortality .\nhowever , in the series of the mayo clinic it was found that kadish stage did not affect the outcome .\ndanish clinicopathological study found that the staging system of kadish was able to stratify into prognostically significant groups . in our study , the 5-year survival rate of these tumors was 26% and median survival time was 23 months .\nthe distribution of onb according to kadish staging system was 16% at stage a , 26% stage b , and 58% stage c. however , in our study , the 5-year survival rates of these stage groups were inferior compared to those reported in other studies .\nthe cause of this poor result was presentation of 5 patients with distant metastases ( 26% ; 2 brain , 1 bone marrow , 2 other sites ) , 4 patients ( 21% ) with cervical lymph node metastasis , 12 patients ( 63% ) with high - grade histology at the time of diagnosis , and inability to evaluate the surgical margins of the resected tumors .\nthe survival rate of node positive patients is 29% compared with 64% of node negative patients .\ndistant metastases have been described in the pancreas , the liver , mediastinum , bone marrow , lungs , leptomeninges , skin , and breasts [ 11 , 12 ] .\ncervical nodal metastases can develop in 17 to 33% of patients and distant metastases in 10 to 40% of patients over the course of disease\nmetastatic disease at presentation occurs in 10 to 50% of patients , depending on the study [ 6 , 13 , 14 ] .\nwe found the local recurrence rate to be 31.5% and distant metastasis 31.5% after initial surgery . during the follow - up periods these groups exhibited distant metastases to the brain , spinal cord , bone , bone marrow , meninges , and lungs .\npatients who had brain and bone marrow metastases had poorer prognosis than others having metastatic deposits of other sites .\ninvolvement of the orbit is a serious prognostic factor , but when the orbital periosteum is affected without penetration into the orbital structures themselves , the eye may be preserved by resection and grafting of the periosteum without an adverse effect on survival as compared with orbital clearance .\nirrespective to the most sophisticated imaging , involvement of the dura and orbital periosteum can accurately be determined only at surgery . in our study ,\nthis group 's ( 8 patients ) survival rate is poorer than those with no involvement of the orbita ( p = .042 ) .\nthe institute of laryngology and otology , university college london , published a study of 42 patients treated over 23 years .\noverall and disease - free survival rates were 77 and 61% at 5 years , and 53 and 42% at 10 years , respectively .\nlate recurrences were seen . based on this experience , combined therapy with craniofacial resection and radiation therapy is recommended by this group . in a retrospective study of 47 patients treated at multiple centers in germany from 1979 to 2001 ,\nthe 5-year overall survival and event - free survival rate were 64% and 50% , respectively .\npatients who received multimodality therapy had a significantly better event - free survival rate compared with those who did not receive multimodality therapy ( 74 versus 41% ) .\nthe authors recommend a combination therapy including ctx , surgery , and postoperative radiation therapy for kadish stage c patients . in our study ,\ninitial treatment included surgery alone in three patients , rt with or without ctx in five , surgery plus postoperative rt in seven , and multimodality therapy ( surgery plus postoperative ctx plus postoperative rt ) in three , only ctx in one patient .\nhowever , in our study choice of treatment modality did not show a statistically significant difference in survival rate .\nthe reasons for that might be including low number of patients in the study , being 5 distant site metastasis , 4 cervical lymph node metastasis at the time of diagnosis , only one orbital exentration ( although there were 8 orbital involvement ) , and 12 patients exhibiting high grade histology and inability to evaluate surgical margins in resected tumors . in conclusion , advanced tumor stage ,\nthe initial histopathologic grade of iii / iv , and involvement of orbita , brain , or bone marrow metastasis were the statistically significant poor prognostic factors , whereas age , sex , and treatment modality were not prognostic factors .", "answer": "objective . \n the aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas . study design . \n retrospective record review . setting . \n istanbul university , cerrahpasa medical faculty , medical oncology outpatient clinic . \n subjects and methods . \n there were 3 stage a tumors , 5 stage b and 11 stage c according to the kadish staging system . \n there were 5 grade i / ii and 12 grade \n iii / iv according to the hyams ' histopathologic system . \n involvement to orbita was detected in eight patients at the time of diagnosis . \n results . \n the median follow - up period was 23.7 months . \n the 5-year survival rate for the whole group was 26% . \n the stage a / b groups exhibited a better survival rate than the c group with 2-year survival rates being 25 versus 71% respectively ( p = .008 ) . \n the grade i / ii groups exhibited a better survival rate than the grade iii / iv groups with 2-year survival rates being 50 versus 16% respectively ( p = .001 ) . \n the group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital . \n conclusion . in our study , \n tumor stage , histopathologic grading , involvement of the orbita , brain and bone marow metastases were the statistically significant prognostic factors .", "id": 233} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a network querying problem , one is given a small network , corresponding to a known pathway or a complex of interest . the goal is to identify similar instances in a large network , where similarity is measured in terms of sequence or interaction patterns .\nprevious approaches to the query problem required precise information on the interaction pattern of the query and were usually limited to small queries ( 24 proteins ) .\npathblast a server for querying linear pathways within a protein protein interaction ( ppi ) network ( 1)was subsequently extended to allow searching for more general structures ( 2 ) .\na general framework for subnetwork querying was developed ( 3 ) , but it is applicable only to very small queries due to its complexity .\ntwo other methods are netmatch , a cytoscape ( 4 ) plugin implementing the work of ferro et al . ( 5 ) that utilizes fast heuristics for subgraph isomorphism to identify approximate matches of queries within a collection of networks , and netgrep ( 6 ) , a system for searching networks for patterns corresponding to small sets of proteins with specified attributes and topology .\nthe torque server implements a novel method for querying protein networks that does not require information on the interconnections ( topology ) among the query proteins ( 7 ) ( figure 1 ) .\nthis makes torque applicable in broader scenarios , such as querying complexes or pathways whose topologies are not completely known , or even when querying from species for which ppi information is not available .\n( 8) also studied queries with no topology information , but since their method is enumerative it was applied to very small queries ( 24 proteins ) .\nit was tested extensively on hundreds of queries of known complexes from a variety of species ( 7 ) .\nit was shown to yield far more matches than the qnet topology - based approach ( 2 ) , while providing results that are highly functionally coherent . \n\nthe network induced by the vertices labeled a , b , c , d and e is a match to the query , where vertex c is an insertion and query element 4 is deleted .\n( a ) the query proteins ; ( b ) the queried network . colored vertices in the network match nodes of the same color in the query .\nthe network induced by the vertices labeled a , b , c , d and e is a match to the query , where vertex c is an insertion and query element 4 is deleted .\nthe torque web server implements the algorithms in ( 7 ) for querying protein sets across species .\nit combines three approaches : a dynamic programming method utilizing color coding , integer linear programming and a fast heuristic based on shortest paths .\ntorque automatically selects the best method to apply at each stage and outputs the highest scoring match .\nscores are based on the underlying network structure , on interaction confidence values and on sequence similarities between matching proteins .\nthe input for torque consists of : \n a query set of proteins in species a;their protein sequences;a ppi network for species b;the sequences of the network proteins . \n \na query set of proteins in species a ; their protein sequences ; a ppi network for species b ; the sequences of the network proteins .\nall inputs are in simple text format : \n the query set can be entered directly as a comma - delimited or whitespace - delimited list.protein sequences are given in the standard fasta format.the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] . \n \nthe query set can be entered directly as a comma - delimited or whitespace - delimited list .\nthe ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .\nit is possible to use a single fasta file ( input 2 ) for many queries , if it contains the sequences for all proteins in all queries .\nwhen the query field is left blank , torque will use all the proteins in input 2 as the query .\nif input 1 contains uniprot protein ids ( www.uniprot.org ) , their sequences need not be entered in input 2 ; instead , torque automatically retrieves them from the uniprot database . for several target species ,\ncurrently , the server supports this option for the three target species saccharomyces cerevisiae , drosophila melanogaster and homo sapiens .\nthe user can indicate one of these target species instead of providing inputs 3 and 4 .\nthe user can control two parameters of the algorithm , setting a trade - off between speed and sensitivity .\nthe user can set the threshold for blast similarity ( e - value ) . by setting a lower threshold , less\nhomologs will be identified for the query proteins , making the algorithm faster but less sensitive .\nthe second parameter is a threshold for the confidence values of ppi network edges provided as part of input 3 .\nedges whose confidence value is lower than the threshold are discarded ; hence , this parameter determines the sparsity of the target network and affects the number of possible matches and the running time .\nthe running time of torque is typically a few minutes , but may be up to an hour , depending on the size and other properties of the query ( for more details , see ( 7 ) ) .\nif several queries are submitted to the server at the same time , they are queued and executed sequentially . rather than waiting for the results online , they can be accessed later , in two ways : \n when a torque job is started , it is assigned a nine - digit job i d .\nthis i d can be used to access the results later from the main torque page.before submitting a query , the user may enter an email address .\nonce torque has finished processing the query , the results will be sent to the email address provided .\nwhen a torque job is started , it is assigned a nine - digit job i d .\nthis i d can be used to access the results later from the main torque page . before submitting a query\nonce torque has finished processing the query , the results will be sent to the email address provided .\nthe web server generates a web page ( figure 2 ) with the image of the top - scoring match for the query in the target network , as well as an auxiliary file in.sif format that can be viewed using the cytoscape software ( 4 ) .\nthe content of the.sif file includes , for each edge , a numerical value representing the confidence in the interaction it represents , as provided in the input .\nthe image shows the subgraph induced by the top - scoring match in the ppi network .\neach vertex is labeled with its protein name in the ppi network and its matching query protein , if such exists .\ninsertion vertices are shown in gray , and proteins from the query for which there was no match in the solution ( deletions ) are listed separately . \n\nthe following example uses as query the mouse dna synthesome complex , downloaded from the corum website ( http://mips.gsf.de/genre/proj/corum/index.html ) . this 13-member complex was queried in the yeast network ( 5430 proteins , 39 936 interactions ) .\nexamining the subnetwork identified by torque we find that it is functionally coherent ( nucleotidyltransferase activity , p < 1.4e 10 ) and significantly intersects the yeast alpha dna polymerase : primase complex , supporting its biological plausibility .\nthe input for torque consists of : \n a query set of proteins in species a;their protein sequences;a ppi network for species b;the sequences of the network proteins . \n \na query set of proteins in species a ; their protein sequences ; a ppi network for species b ; the sequences of the network proteins .\nall inputs are in simple text format : \n the query set can be entered directly as a comma - delimited or whitespace - delimited list.protein sequences are given in the standard fasta format.the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] . \n \nthe query set can be entered directly as a comma - delimited or whitespace - delimited list .\nthe ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .\nit is possible to use a single fasta file ( input 2 ) for many queries , if it contains the sequences for all proteins in all queries .\nwhen the query field is left blank , torque will use all the proteins in input 2 as the query .\nif input 1 contains uniprot protein ids ( www.uniprot.org ) , their sequences need not be entered in input 2 ; instead , torque automatically retrieves them from the uniprot database . for several target species ,\ncurrently , the server supports this option for the three target species saccharomyces cerevisiae , drosophila melanogaster and homo sapiens .\nthe user can indicate one of these target species instead of providing inputs 3 and 4 .\nthe user can control two parameters of the algorithm , setting a trade - off between speed and sensitivity .\nthe user can set the threshold for blast similarity ( e - value ) . by setting a lower threshold , less\nhomologs will be identified for the query proteins , making the algorithm faster but less sensitive .\nthe second parameter is a threshold for the confidence values of ppi network edges provided as part of input 3 .\nedges whose confidence value is lower than the threshold are discarded ; hence , this parameter determines the sparsity of the target network and affects the number of possible matches and the running time .\nthe running time of torque is typically a few minutes , but may be up to an hour , depending on the size and other properties of the query ( for more details , see ( 7 ) ) .\nif several queries are submitted to the server at the same time , they are queued and executed sequentially . rather than waiting for the results online , they can be accessed later , in two ways : \n when a torque job is started , it is assigned a nine - digit job i d .\nthis i d can be used to access the results later from the main torque page.before submitting a query , the user may enter an email address .\nonce torque has finished processing the query , the results will be sent to the email address provided .\nwhen a torque job is started , it is assigned a nine - digit job i d .\nthis i d can be used to access the results later from the main torque page . before submitting a query\nonce torque has finished processing the query , the results will be sent to the email address provided .\nthe web server generates a web page ( figure 2 ) with the image of the top - scoring match for the query in the target network , as well as an auxiliary file in.sif format that can be viewed using the cytoscape software ( 4 ) .\nthe content of the.sif file includes , for each edge , a numerical value representing the confidence in the interaction it represents , as provided in the input .\nthe image shows the subgraph induced by the top - scoring match in the ppi network .\neach vertex is labeled with its protein name in the ppi network and its matching query protein , if such exists .\ninsertion vertices are shown in gray , and proteins from the query for which there was no match in the solution ( deletions ) are listed separately . \n\nthe following example uses as query the mouse dna synthesome complex , downloaded from the corum website ( http://mips.gsf.de/genre/proj/corum/index.html ) .\nthis 13-member complex was queried in the yeast network ( 5430 proteins , 39 936 interactions ) .\nexamining the subnetwork identified by torque we find that it is functionally coherent ( nucleotidyltransferase activity , p < 1.4e 10 ) and significantly intersects the yeast alpha dna polymerase : primase complex , supporting its biological plausibility .\nthe torque web server allows users to run topology - free queries on predefined or user - provided target networks .\nthe result is a subnetwork of the target network most similar to the query , and is presented both graphically and as a downloadable text file .\n) ; german - israel foundation grant ( to r.s . ) ; postdoctoral fellowship from the edmond j. safra bioinformatics program at tel aviv university ( to f.h . ) . funding for open access charge", "answer": "torque is a tool for cross - species querying of protein \n protein interaction networks . it aims to answer the following question : given a set of proteins constituting a known complex or a pathway in one species , can a similar complex or pathway be found in the protein network of another species ? to this end , torque seeks a matching set of proteins that are sequence similar to the query proteins and span a connected region of the target network , while allowing for both insertions and deletions . unlike existing approaches \n , torque does not require knowledge of the interconnections among the query proteins . \n it can handle large queries of up to 25 proteins . \n the torque web server is freely available for use at http://www.cs.tau.ac.il/bnet/torque.html .", "id": 234} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin europe , prostate cancer ( pca ) is the most common malignancy in males and the third most common cause of cancer mortality .\ncurrently , more extensive and earlier diagnosis has led to a decrease in pca related mortality [ 1 , 2 ] . despite an extended search for a more specific biomarker than prostate specific antigen ( psa ) , psa still remains the only widely employed diagnostic and follow - up marker for pca .\nthe predictive capability of the 4 ng / ml psa threshold as a biopsy indicator is deficient since 2040% of pca cases are thereby missed .\nthus , other accurate diagnostic pca biomarkers , especially for aggressive and potentially life - threatening pca , are needed .\nsince increased aerobic glycolysis or the warburg effect has been identified as common to neoplastic cells , this mechanism promises potential for diagnostic and therapeutic targets .\nthe enzyme transketolase - like 1 ( tktl1 ) , therefore , comes into investigational focus since it is a crucial enzyme for sugar fermentation , linking glucose and fat metabolism without pyruvate dehydrogenase [ 6 , 7 ] .\nwhen overexpressed , tktl1 activates the pentose phosphate pathway ( ppp ) , accelerating tumor cell growth and supporting tumor survival and systemic dissemination .\naccordingly , an assay was developed to evaluate tktl1 based on the fluorometric epitope detection of specific antibodies in cd14/cd16 positive monocytes , following tumor cell phagocytosis and digestion ( edim - test ) .\nstill , the role of tktl1 as a cancer biomarker is controversial [ 10 , 11 ] and the edim - test has not been approved for routine clinical application . nevertheless ,\nthough tktl1 does not play a role in conventional medicine , it has gained high popularity in alternative / complementary medicine , not only as a diagnostic but also as a prediction marker to assess the risk of metastatic progression .\nthe goal of the current investigation was to compare the tktl1 serum level in patients with a clinically localized pca to that in healthy controls .\nfurthermore , the investigation was directed towards establishing whether the tktl1 serum level correlates with clinical and histologic parameters of the tumor , thus facilitating identification of patients harboring life - threatening disease requiring definitive treatment . for this purpose ,\nthe serum concentration of tktl1 in pca patients and healthy controls was analyzed by means of an enzyme - linked immunosorbent assay ( elisa ) , which is a highly standardized detection system , and correlated to clinical and histologic parameters .\npatients ( n = 66 ) undergoing curative radical prostatectomy ( rpe ) for biopsy - proven pca in the department of urology , goethe - university , frankfurt am main , germany , were included in the investigation . controls ( n = 10 ) were healthy , age - matched , male volunteers .\nfirstly , 10 ml peripheral blood was drawn from patients several days before surgery and from controls .\nblood samples were allowed to coagulate and then centrifuged at 3000 rpm at + 4c for 10 minutes .\nthe concentration of tktl1 was determined in pca patient and control serum using a commercially available elisa kit ( seh018hu , cloud - clone corp , houston , tx , usa ; sensitivity : < 0.055 ng / ml with no significant cross - reactivity or interference between tktl1 and analogues ) .\nall assays were done in duplicate and the concentration was calculated from a standard curve using a 4-parameter curve fit ( magellan software , tecan ) .\nunivariate analysis was performed by the wilcoxon - man - whitney - test for comparison between two groups and the kruskal - wallis - test with the iman - conover - method ( bonferroni - holm - corrected ) for more than two groups .\nhanns ackermann , epsilon - publishers , frankfurt , germany ) . the null hypothesis ( tktl1 concentration in serum of pca patients does not differ from that of healthy volunteers ) was rejected if p - values were less than 0.05 .\nthe clinical tumor stage was classified according to the 7 edition of the ajcc and the pathologic tumor stage was determined according to the 6 edition of the tnm classification .\nimaging was carried out according to the currently valid guidelines of the european association of urology .\nthe median age at tumor diagnosis was 66 years ( range 4688 ) and the median serum psa was 8.0 ng / ml ( range 1.857.0 ) ( median age control group : 60 years ( 5572 ) ; control psa : 2.8 ng / ml ( 2.04.0 ) . nearly all pcas submitted to surgery were clinically significant .\nnone of the patients had evident clinical signs of infection or acute or chronic inflammation at surgery .\nclinical and histopathological demographics of 66 pca patients values expressed as median with range or number ( % ) .\nrpe radical prostatectomy ; dre digital rectal examination , psad psa density univariate analysis of the elisa investigation demonstrated that serum tktl1 was significantly lower in the serum of pca patients , compared to healthy controls ( p=0.0001 , effect size indicator r = z / sqr(n ) = 0.4179 , figure 1 ) .\nhowever , correlation between serum tktl1 and serum psa ( p = 0.38 ) , biopsy and prostatectomy gleason sum ( p = 0.79 and 0.89 , respectively ) , prostate volume ( p = 0.23 ) , psa density ( p = 0.80 ) , clinical and pathologic t - stage ( p = 0.66 and 0.65 ) , highest gleason pattern in the biopsy and prostatectomy specimen ( p = 0.83 and 0.74 , respectively ) , upgrade of gleason sum from biopsy to prostatectomy ( p = 0.86 ) , pn- , l- , v- , n- and r status ( p = 0.32 , 0.88 , 0.30 , 0.90 and 0.32 , respectively ) , extracapsular extension , seminal vesicle invasion as well as d`amico classification ( p = 0.75 , 0.89 and 0.34 , respectively ) did not reach statistical significance . tktl1 serum concentration ( ng / ml ) in pca patients and controls .\nbox : lower line quartile q1 ( 25% quantile ) ; middle line \ntktl1 , as evaluated by the edim - test , has been propagated as a reliable cancer biomarker , since a positive correlation between tktl1 expression and tumor progression has been reported .\nhowever , investigations negating the reliability of tktl1 have also been published [ 11 , 13 ] , making a definitive assessment regarding tktl1 reliability as a biomarker questionable .\nindeed , the decreased serum tktl1 found in pca patients in the present investigation stands in opposition to the increase in monocyte associated tktl1 claimed by the proponents of the edim - test .\nhowever , the different methods and localities , where tktl1 was measured , in serum and in macrophages , could account for the differing results . speculatively , assuming the accuracy of the edim test together with the theoretical background proposed by coy and colleagues , an inverse correlation between tktl1 detected in macrophages and extracellular tktl1 in serum could occur , since tumor cells undergo phagocytosis .\ntktl1 could therefore be sequestered in macrophages and the tktl1 level in serum be reduced . still , this hypothesis is speculative and requires further evaluation .\nalthough , in the present investigation , serum tktl1 levels differed in cancer patients and healthy persons , no correlation was apparent between serum tktl1 and clinical or pathologic parameters .\nconflicting reports about tktl1 expression associated with various cancer entities and clinical outcome have been published by several investigators [ 10 , 13 , 14 ] .\ntktl1 , determined with the same immunohistochemical method in colorectal cancer tissues , has been positively associated with tumor progression and tktl1-expression level in one study , whereas another study pointed to a significant decrease in tktl1-expression associated with metastasis .\nrecently , the dna demethylating agent 5-aza-2'-deoxycytidine ( 5-aza ) has been reported to augment expression of tktl1 in melanoma cells and was associated with enhanced invasion of the tumor cells , whereas others have demonstrated reduced invasion of melanoma cells under 5-aza treatment .\ngrimm et al . correlated an increase of edim scores with a metabolic shift from aerobic to anaerobic conditions , whereas this correlation could not be confirmed by others .\npossibly , these inconsistencies have led to the recommendation of combining tktl1 quantification with a standardized panel of established blood biomarkers .\nthe ambivalence of tktl1 expression in so many different investigations shows that the role of tktl1 may be more complex than initially thought .\nthis study was designed as a pilot investigation and thus includes a limited number of patients .\nsince patients only underwent a general health check , this could contribute to a potential , though unlikely , bias for the high serum tktl1 expression found in this cohort .\nthe study was designed to assess the diagnostic potential of tktl1 , not its prognostic ability . since pca , in most cases ,\nis associated with slow progression , long - term follow - up would be required to follow the course of serum tktl1 during the course of the disease .\nserum tktl1 was decreased in patients with clinically localized pca , but failed to facilitate identification of patients with aggressive disease , who might particularly benefit from definitive cancer treatment .\nbased on these results , we can not currently advise introducing serum tktl1 into clinical practice .\nfurther long - term studies including larger patient cohorts and simultaneous measurement of serum tktl1 and macrophage sequestered tktl1 are warranted to clarify the role of tktl1 in pca and resolve its applicability as a pca biomarker .", "answer": "introductionmonocyte associated transketolase - like 1 ( tktl1 ) as a cancer biomarker has become popular with alternative practitioners , but plays no role in conventional medicine . \n this investigation evaluates the potential of serum tktl1 as a biomarker for prostate cancer.material and methodspatients ( n = 66 ) undergoing curative radical prostatectomy ( rpe ) for biopsy - pro - ven pca were included in the study . \n controls ( n = 10 ) were healthy , age - matched , male volunteers \n . 10 ml of peripheral blood was drawn from patients several days before surgery and from controls . \n serum tktl1 was measured using the elisa method.resultsthe median age at tumor diagnosis was 66 years and median serum psa was 8.0 ng / ml . nearly 96% of pcas submitted to surgery were clinically significant . compared to healthy controls , serum tktl1 was significantly lower in pca patients ( p = 0.0001 , effect size indicator r = z / sqr(n ) = 0.4179 ) . \n no correlation was apparent between serum tktl1 and serum psa , gleason sum , tumor stage or further clinical and pathologic parameters.conclusionsreduced serum tktl1 in pca patients stands in opposition to tktl1 epitope detection in monocytes ( edim ) based studies , whereby increased tktl1 in monocytes of tumor patients has been reported . since serum tktl1 \n does not correlate with clinical parameters in the current investigation , further research is needed to clarify whether serum tktl1 has potential as a biomarker for pca .", "id": 235} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nplacenta accreta is a pathology characterized by abnormal and firm attachment of the placenta to the myometrium.1 the depth of penetration of the placental villi into the myometrium defines three severity levels of placenta accreta ; accreta , increta , and percreta .\naccreta , the least severe and most common of the three , occurs when the placental villi attach directly to the myometrium rather than to the decidua basalis .\npercreta , the most rare and severe manifestation of accreta , is the invasion of the placental villi through the entire thickness of the myometrium , and even further.2 placenta accreta tends to reoccur ; however , little is known regarding the pathophysiological processes leading to this invasive placentation .\nthe most severe complication of placenta accreta is spontaneous rupture of the uterus , which poses diagnostic challenges and management dilemmas , and can be a life - threatening event to the mother and fetus .\nherein , we describe a woman diagnosed with repeated placenta accreta that was complicated by spontaneous rupture of the uterus .\nthis case demonstrates increasing placental invasiveness and , to the best of our knowledge , is a first report of this kind .\nfurthermore , repeated invasive placentation occurred at the same site , and not at the cesarean section ( cs ) scar , which raises a fundamental question regarding the mechanism of trophoblast implantation and location of recurrence of placenta accreta .\nunderstanding the processes that influence the timing and location of this life - threatening complication may set the basis for better diagnosis and management protocols .\na 32-year - old woman in her fourth pregnancy , with parity of 2 , presented at 19 weeks gestation to the gynecologic emergency department with lower abdominal pain for the past 2 days .\nher obstetric history included retained placenta in both first and second deliveries , which necessitated manual revision of the uterine cavity and curettage .\nshe had a perforation of the left posterior uterine wall during curettage in her second delivery that was laparoscopically repaired . in her third pregnancy\n, she presented with an acute abdomen at 19 weeks gestation and underwent exploratory laparoscopy that demonstrated a 2.5 cm rupture in the posterior uterine wall at the site of the previous perforation .\nlaparoscopy was turned into laparotomy ; the rupture was sutured and the patient recovered well . magnetic resonance imaging ( mri )\nperformed at 21 weeks gestation demonstrated placental tissue penetrating , but not perforating , the myometrium of the posterior uterine wall , which was indicative of placenta increta ( figure 1 ) .\nafter counseling , the couple chose to terminate the pregnancy , and hysterotomy was performed at 22 weeks gestation . in the current pregnancy , upon admission to the emergency department ,\nthe patient presented normal vital signs , and the gynecologic examination revealed 19 weeks gestation \nthis suspicion raised by sonography , together with the patient s history , prompted an mri at 24.2 weeks that demonstrated the presence of placenta percreta at the site of the previous placenta increta ( figure 2a ) . following counseling , the couple decided to continue the pregnancy , and the patient was hospitalized for observation .\nrapid bedside ultrasound examination demonstrated intraabdominal bleeding , and emergency cs was performed . during laparotomy ,\nmassive intraabdominal bleeding was observed , originating from a uterine rupture with a perforating placental tissue ( figure 2b ) .\nfollowing the delivery of the fetus and complete placental removal , as well as suturing of the uterine wall , the bleeding stopped and hysterectomy was avoided .\nthe mother recovered well , while her neonate died of prematurity complications . due to the ominous nature of the patient s obstetric history ,\nplacenta accreta , at any level of severity , is a rare obstetric complication with an estimated incidence of between 1 in 533 ( as reported by wu et al3 ) and 1 in 2,500 pregnancies ( as reported by miller et al1 ) .\nhowever , once placenta accrete is diagnosed , it has a tendency to reoccur in subsequent pregnancies.4,5 little is known about recurrence of placenta accreta , and specifically its location , histopathological invasiveness , and prognosis .\nthe only known risk factor for repeated placenta accreta is parity.6 here we report , for the first time , a case of four consecutive pregnancies complicated by abnormal placentation . in primary placenta accreta , the strongest independent risk factor has been found to be previous cs.1,7 this is explained by the tendency of implantation and placentation to occur in the scarred area.1 in the case presented here , recurrence occurred in the left uterine cornu , the site of the previous placenta increta , rather than the cs scar .\nadditionally , the clinical manifestation was aggravated with each consecutive pregnancy : retained placenta necessitating manual lysis and curettage in the first and second , placenta increta in the third , and spontaneous uterine rupture due to placenta percreta in the fourth .\ntherefore , this case presents not only placenta accreta recurrence but also increased invasiveness of the placentation .\neven though placentation is prone to develop within previous cs scars , other prior uterine injuries may play a similar role , and hence are considered to be a risk factor for placenta accreta.7 it is not known whether injury location affects the risk for placenta accreta . the correlation between scarred uteri and placenta accreta\nis explained by a relative hypoxic environment in the scar tissue8 or the histologically abnormal structure of the scar .\nthis abnormal structure is characterized by defective re - epithelialization and relative abundance of extracellular matrix.9 alternatively , prior uterine injury is associated with dynamic changes in decidual leukocyte distribution,10 which subsequently affects the homing of the blastocyst to its implantation site .\nonce placenta accreta is diagnosed , proper counseling and discussion with the patient should be undertaken regarding further management of the pregnancy in light of the complications involved.11 the most severe complication is spontaneous rupture of the uterus , as seen in this case , which poses both a diagnostic challenge and an immediate risk to the life of both mother and fetus .\nthe incidence of spontaneous uterine rupture is reported to be approximately one in 5,000 ; however , this includes etiologies other than placenta accreta.12 uterine rupture due to placenta accreta is extremely rare , and a systematic review of reported cases is yet to be done . in the past ,\nmost cases were managed by hysterectomy , but conservative treatment is becoming common recently.13,14 during the operation , active bleeding stopped promptly and the patient remained hemodynamically stable . completing the procedure outweighed the risk of blood loss involved in hysterectomy , and uterine repair was technically feasible .\nthe location where spontaneous uterine rupture occurs has not been thoroughly studied ; however , some reports associate first trimester ruptures with the fundus and third trimester ruptures with the lower uterine segment.15 in case of previous cs , the rupture usually occurs at the site of the old scar.12 in our patient , the rupture appeared in the left uterine cornu , where the placenta was invading through the myometrium , rather than in the cs scar .\nthis could be explained by the fact that the uterine wall was already disrupted by the placenta percreta prior to the rupture , as was seen in the mri . as with rupture location , factors affecting the timing of uterine rupture due to placenta accreta\nwhile it is well established that spontaneous uterine rupture usually occurs in the third trimester,15 there have been reports of first8 and second1619 trimester ruptures as well . in our case , spontaneous rupture occurred at 24 weeks gestation ; a critical time for the fetus .\nthis gestational age marks the limit of viability , since preterm delivery around this time results in 50% long - term survival probability of the newborn.20 in the face of immediate risk for the mother , urgent cs was inevitable , even when considering the probable prematurity complications for the fetus . with the increase in conservative management of placenta percreta\nalthough systematic reviews of these complications are not yet available , this insight should be taken into account during counseling following conservative management of placenta accreta .\nnotes : transabdominal two - dimensional ultrasound in the transverse plane showing an abnormal placenta with thinning of the myometrium in the left posterior uterine wall , indicated by an asterisk .\nsimilar findings are seen in the longitudinal plane in addition to fundal placental lacunas ( arrow head ) with increased blood flow by color doppler scanning .", "answer": "placenta percreta is an obstetric condition in which the placenta invades through the myometrium . \n this is the most severe form of placenta accreta and may result in spontaneous uterine rupture , a rare complication that threatens the life of both mother and fetus . in this case report , we describe a 32-year - old woman in her fourth pregnancy , diagnosed with repeated placenta accreta , which was eventually complicated by spontaneous uterine rupture at 24 weeks gestation . \n this patient had a history of abnormal placentation in prior pregnancies and previous uterine injuries . \n this case demonstrates a pattern of escalating placental invasiveness , and raises questions regarding the process of abnormal placentation and the manifestation of uterine rupture in scarred uteri .", "id": 236} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe countermovement jump ( cmj ) is an explosive movement that is essential in many sports , \n including basketball and volleyball1 .\ncmj \n height , which is determined by measuring the jump height starting from an erect position \n followed by a downward movement before starting to push off , is an important criterion in \n athletic evaluation .\nathletes spend much time and effort in various training activities to \n improve their athletic performance2 .\nmany \n researchers have reported the performance characteristics of the cmj and have discussed \n multiple issues related to achieving better cmj height3,4,5 .\nugrinowitsch et al.6 reported that better \n cmj height was the result of an increased vertical shift in the body s center of mass . to \n improve cmj performance , ankle flexibility4 ,\nmuscle strength3 , 7 , 8 , \n initial jumping posture ( squat depth)5 , \n and take - off velocity during vertical jump1 are required .\nrobertson and fleming9 investigated the contributions of the extensors in the lower limb \n and found that the greatest contributor to jump performance was the hip ( 40% ) followed by \n the ankle ( 35.8% ) and the knee ( 24.2% ) . furthermore , another study suggested that ankle \n joint flexibility contributes significantly to increasing cmj height4 . during a vertical jump , the contribution of the ankle joint \n depends on the torque produced by the plantar flexors as well as the ankle dorsiflexion \n range of motion ( df rom)10 .\ntoe flexor muscles ( tfm ) , which support the longitudinal arch of the foot against the \n reaction of the floor on the forefoot , also affect athletic performance11 .\nprevious studies reported that tfm strengthening may have \n a positive effect on athletic performance7 , 12 .\nin addition , tfm strength may affect the \n use of the metatarsophalangeal joint ( mpj ) before take - off during the cmj10 . to date\n, no studies on the effects of tfm \n strength on cmj height have been conducted .\ntherefore , this study investigated the correlations between peak tfm strength , df rom , and \n cmj height .\nthe results of this study may help identify the factors for improving cmj height \n in training athletes .\neighteen healthy volunteers ( age : 23.3 2.5 years , body weight : 71.9 11.2 kg , height : \n 174.6 3.8 cm , df rom : 19.6 3.9 , cmj height : 46.3 10.3 cm ) participated in this study . \n\nall participants were free of injuries , especially in the ankle joints , feet , and mpj .\nthe \n exclusion criteria were ( 1 ) any cardiovascular , respiratory , abdominal , neurological , \n musculoskeletal , or other chronic disease and ( 2 ) any symptoms that could affect the \n musculoskeletal system .\nthe study procedure was approved by the yonsei university wonju \n campus human studies committee ( approval number : 1041849 - 201508-bm-018 - 03 ) ; all participants \n provided written informed consent before enrollment .\npeak tfm strength , df rom , and cmj height were used as the variables in this \n cross - sectional study .\neach participant s body weight and height were determined at the \n beginning of the test protocol .\nprior to gathering data , participants performed a warm - up \n that consisted of 5 minutes of walking up and down the stairs .\nthree cmjs were performed by each \n participant , and the mean value ( mean cmj height ) was used for analysis .\npeak tfm strength was measured using a digital dynamometer ( msc-200 , ametec inc , largo , fl , \n usa ) . for a stable measurement setting\n, the digital dynamometer was attached to a wooden \n frame consisting of a platform , a vertical board , and a footboard13 , 14 .\neach \n participant was instructed to sit comfortably with his or her back supported by a chair \n backrest and to place the foot to be tested on the footboard .\nthe hip , knee , and ankle \n joints were positioned at 90 during the test .\nthe toe to be measured was inserted into a \n leather cuff that was placed on the plantar side of the proximal phalanx , and the \n participant was instructed to pull the cuff downward as hard as possible for 5 seconds .\neach \n of the 5 toes ( phalanges ) was measured 3 times in the same way .\nfor familiarization with the \n testing procedure , participants were allowed to practice before measurement . for analysis\n, \n the highest value of 3 tfm strength measurements in each toe was used .\na 3-minute rest \n period was provided between the strength measurements of each toe to minimize muscle \n fatigue . a blinded tester with experience working with a digital dynamometer read and \n recorded the strength value for each tfm on the digital display to eliminate experimental \n bias ( table 1table 1.mean ( sd ) of peak toe flexor muscle strengths by participants ( n=18)first toesecond toethird toefourth toefifth toepeak tfm strength13.1 3.93.1 1.02.8 0.83.1 1.0 4.2 1.3values are presented as the mean sd .\ntfm : toe flexor muscle the maximal df rom of the dominant leg was measured with a universal goniometer in 1 \n increments with the participant lying prone with 90 knee flexion .\none lever of the \n goniometer was positioned on the proximal fibular head , while the pivot was placed on the \n lateral malleolus .\nthe measuring arm was positioned on the fifth metatarsal bone , and its \n position was used to determine the passive df rom15 .\nparticipants were instructed to perform 3 maximal cmjs with the use of both arms , trying to \n cover the longest possible vertical distance .\nthe highest successful cmj height among the 3 attempts of each participant was chosen \n for jump height analysis7 .\ntwo - dimensional \n ( 2d ) kinematics measurement was obtained during the procedure with regular sampling at \n 25 hz .\na camera ( canon 500d , tokyo , japan ) was mounted on a tripod , which was placed 5 m \n away from the participants , to record movements in the sagittal plane .\na marker was placed on the sacrum at the \n approximate center of mass ( com ) , and the camera lens was focused on each participant s \n sacral marker in the standing position16 . \n\nvideo \n sequences were digitized and examined using virtualdub software ( avery lee , version 1.5.10 , \n cambridge , ma , usa ; http://www.virtualdub.org/ ) .\nthe images were then analyzed using the \n imagej computer program ( national institutes of health , bethesda , maryland usa ; \n http://rsb.info.nih.gov/nih-image ) for height comparison .\nthe data were analyzed using pasw version 18.0 ( chicago , il , usa ) for windows .\npearson \n correlation coefficients ( r ) were used to determine the strength and directionality of the \n relationships among the variables ( peak tfm strength , df rom , and cmj height ) .\nmukaka17 suggested threshold values of 0.00.3 , \n 0.30.5 , 0.50.7 , 0.70.9 , and 0.91.0 for negligible , low , moderate , high , and very high \n correlation coefficients , respectively .\nin addition , the coefficient of determination \n ( r ) was used to account for the variation among the variables . in all \n analyses ,\ntable 2table 2.correlation coefficients between peak tfm strength , df rom , and cmj \n heightfirst tfmsecond tfmthird tfmfourth tfmfifth tfmdf romcmj heightfirst tfm strength1.0second tfm strength0.161.0third tfm strength0.0820.7011.0fourth tfm strength0.2280.5030.7901.0fifth tfm strength0.2080.6250.6230.5851.0df rom0.7100.2190.1860.0070.0291.0cmj height0.7650.0210.2330.1020.0630.6421.0*p<0.05 ; * * p<0.001 .\ncmj : countermovement jump , df rom : ankle dorsiflexion range of motion , tfm : toe \n flexor muscle shows the pearson s correlation coefficients between peak tfm strength , df \n rom , and cmj height in the participants . cmj height showed a moderate correlation with df \n rom ( r=0.642 , r=41.3% , p<0.001 ) and a high correlation with peak first tfm \n strength ( r=0.765 , r=58.5% , p<0.001 ) .\nthe relationships between cmj height \n and peak tfm strength of the other toes were negligible ( r=0.021 to 0.233 , p>0.05 ) . * p<0.05 ; * * p<0.001 .\ncmj : countermovement jump , df rom : ankle dorsiflexion range of motion , tfm : toe \n flexor muscle\nthe results of this study indicate that cmj height is correlated with peak first tfm \n strength and df rom in healthy subjects .\nseveral previous studies investigated multiple issues related to cmj and reported a \n proximal - to - distal sequence of muscle activation \nhip extensors , followed by knee extensors \n and finally ankle plantar flexors3 , 18and a proximal - to - distal transfer of \n energy during jumping10 , 19 .\npapaiakovou4 reported that the ankle should be a key joint in transmitting the \n energy generated by the proximal part ( hip extensor , knee extensor , and ankle plantar \n flexor ) to the ground during cmj execution .\nhowever , the mpj is smaller than the other \n joints in the leg , but the mpj force amounts to about 86% body weight during push - off in the \n gait cycle20 .\nthe tfm around the mpj may \n have a profound effect on forefoot loading and force transmission21 , and improvements of tfm strength training may have a \n significant effect on athletic performance enhancement7 , 12 .\nthe results of this study indicate a high correlation between peak first tfm strength and \n cmj height ( r=0.765 , r=58.5% , p<0.001 ) .\ncohen22 reported that the coefficient of determination could be used to \n more fully interpret the r value .\nthus , 58.5% of the total variation in peak first tfm \n strength can be explained by variation in cmj height .\nnihal et al.23 reported that dancers had greater hallux muscle strength \n than non - dancers ( 7 4n vs. 6 4n , respectively ; p<0.049 ) . in addition , the first tfm \n strength was twice the second tfm strength ( 9 4n vs. 4 1n , respectively ; p<0.001 ) . \n furthermore ,\ntanaka et al.24 demonstrated \n that the tfm are important contributors to sustaining dynamic balance ; in particular , the \n tfm of the hallux was greater than the sum of the others combined . tfm strength may \n influence mpj stiffness before take - off during cmj performance .\nstefanyshyn and nigg10 reported that increasing mpj stiffness \n would decrease the energy lost at the mpj , which would correspond to a positive effect on \n jump height .\nthis finding may indicate a lack in the peak first tfm strength leading to a \n large amount of energy loss and , therefore , would not adequately transmit energy via the \n lower limb extensors before take - off during a cmj .\nthus , the results of this study suggest \n that the peak first tfm strength is an important factor not only in stabilization of the \n forefoot but also in the transmission of energy generated from the lower limb extensors to \n the ground , as well as in improving athletic performance ; it is a major contributor in \n performing a higher cmj .\ndf rom during a full squat before take - off was reported to affect cmj height25 . in this study ,\ncmj height showed a \n moderate positive correlation with df rom ( r=0.642 , r=41.3% , p<0.001 ) , \n consistent with the results of a previous study4 .\nindividuals with a greater df rom were reported to have the ability \n to place their heels in contact with the ground during a full squat , which causes the ankle \n plantar flexor muscles to achieve sufficient force - generating capacity for a deeper squat \n position before take - off4 .\nit has been \n shown that an active muscle , when lengthened , may sustain high forces and stretch the tendon \n sufficiently so that it can store elastic energy for the late concentric phase when the \n muscle activity starts to decay26 . \n\nhowever , studies have shown that people lacking df rom raised their heels off the ground , \n had greater horizontal shift rather than vertical shift of com , and achieved a low jump \n height25 , 26 .\nthus , df rom is thought to be a second contributor to achieving \n sufficient force - generating capacity and proper vertical shift of com during cmj \n performance .\nfirst , the participants performed the experiment \n barefoot , but they wear shoes for actual athletic activities .\nsecond , other related muscles \n that may contribute to the cmj , including the ankle plantar flexors , knee extensors , and hip \n extensors , were not investigated .\nhowever , this \n study is the first to examine the relationship between peak tfm strength and cmj height . \n further study is needed to investigate the correlation between peak tfm strength and ankle \n plantar flexors .\nsecond , further research will need to examine whether improvement in peak \n tfm strength and df rom can have a clinically useful impact on cmj performance .\nthis study was performed to investigate the correlations between df rom , peak tfm strength , \n and cmj height .\nthe results of this study indicate that the peak first tfm strength and df \n rom are the main contributors to cmj performance .\nmeasuring the strength of peak first tfm , \n ankle plantar flexors , knee extensors , and hip extensors in the lower limb and df rom may be \n useful in clinical practice for improving jump performance in athletes such as volleyball \n and basketball players .", "answer": "[ purpose ] this study assessed the relationships between peak toe flexor muscle strength , \n ankle dorsiflexion range of motion , and countermovement jump height . [ subjects and \n methods ] eighteen healthy volunteers participated in the study . \n each participant completed \n tests for peak toe flexor muscle strength , ankle dorsiflexion range of motion , and \n countermovement jump height . \n [ results ] the results showed ( 1 ) a moderate correlation \n between ankle dorsiflexion range of motion and countermovement jump height and ( 2 ) a high \n correlation between peak first toe flexor muscle strength and countermovement jump height . \n \n peak first toe flexor muscle strength and ankle dorsiflexion range of motion are the main \n contributors to countermovement jump performance . \n [ conclusion ] these findings indicate \n that the measurement of peak first toe flexor muscle strength and ankle dorsiflexion range \n of motion may be useful in clinical practice for improving jump performance in athletes \n training for sports such as volleyball and basketball .", "id": 237} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthree fruiting bodies of t. matsutake were used to measure the number of spores produced from each fruiting body .\nthe samples used for the enumeration of spores were similar in size used for the investigation of spore dispersion , and their veils under each pileus had just started to open .\nwe cut the stem of each mushroom and set the pileus above a piece of aluminum foil for 4 days to obtain spore prints .\nall of the spores on the foil were collected and measured for weight , and the numbers of spores in a serial - diluted solution were enumerated using a haemacytometer .\nthe experimental site was mainly composed of 65-year - old japanese red pines ( pinus densiflora s. et z. ) , although a few oaks ( quercus variabilis bl . ) occupied less than 20% .\nthe site had been surveyed for mushroom growth for more than 4 yr , and the locations of pine mushroom had been thoroughly documented .\nonly one fruiting body of t. matsutake remained within each site ; all others , including other mycorrhizal mushrooms , were thoroughly removed .\nwe established three sites for study , and the distances from each site were more than 50 m. we established 48 slide glasses coated with glycerin nearby each fruiting body in four directions separated by four different distance intervals at three heights .\nthe distances were set as 50 , 100 , 200 and 500 cm from the fruiting body . at each point\n, we installed a stick containing three slide glasses that were 0 , 50 and 100 cm above the ground .\nthe dispersed spores were collected from the time immediately after the veils of pileus were torn out .\nwe installed the collecting glasses when the fruiting body was hemispherical and stopped when it became planar , a total of 4 days as described by ka et al . .\nthe slide glasses were installed at 10 am every day and were replaced by a new one after 24 hr .\nthe number of spores on each slide was enumerated by the line - transect method under a microscope ( 400 ) using an image analyzer ( leica , sasem onairtv ) .\nthe plate was overlapped by grids of 116 m118 m for counting , and triplicates were applied for the enumeration .\nthree fruiting bodies of t. matsutake were used to measure the number of spores produced from each fruiting body .\nthe samples used for the enumeration of spores were similar in size used for the investigation of spore dispersion , and their veils under each pileus had just started to open .\nwe cut the stem of each mushroom and set the pileus above a piece of aluminum foil for 4 days to obtain spore prints .\nall of the spores on the foil were collected and measured for weight , and the numbers of spores in a serial - diluted solution were enumerated using a haemacytometer .\nthe experimental site was mainly composed of 65-year - old japanese red pines ( pinus densiflora s. et z. ) , although a few oaks ( quercus variabilis bl . ) occupied less than 20% .\nthe site had been surveyed for mushroom growth for more than 4 yr , and the locations of pine mushroom had been thoroughly documented .\nonly one fruiting body of t. matsutake remained within each site ; all others , including other mycorrhizal mushrooms , were thoroughly removed .\nwe established three sites for study , and the distances from each site were more than 50 m. we established 48 slide glasses coated with glycerin nearby each fruiting body in four directions separated by four different distance intervals at three heights .\nthe distances were set as 50 , 100 , 200 and 500 cm from the fruiting body . at each point\n, we installed a stick containing three slide glasses that were 0 , 50 and 100 cm above the ground .\nthe dispersed spores were collected from the time immediately after the veils of pileus were torn out .\nwe installed the collecting glasses when the fruiting body was hemispherical and stopped when it became planar , a total of 4 days as described by ka et al . .\nthe slide glasses were installed at 10 am every day and were replaced by a new one after 24 hr .\nthe number of spores on each slide was enumerated by the line - transect method under a microscope ( 400 ) using an image analyzer ( leica , sasem onairtv ) .\nthe plate was overlapped by grids of 116 m118 m for counting , and triplicates were applied for the enumeration .\nthe fruiting bodies used for spore counting were 230 22 g in fresh weight , 12 0.3 cm in pileus diameter , 15 0.3 cm in stipe length and 3.5 0.1 cm in stipe diameter .\nalthough the fruiting bodies were relatively larger and heavier than generally harvested mushrooms as goods , they could be considered as representative fruiting bodies of overmatured mushrooms .\nthe spores collected from each fruiting body reached about 150 mg in total mass and were counted as 4.5~5 billion , which varied depending on the size of the mushroom .\nalthough we set the slide glasses at three heights ( 0 , 50 and 100 cm above the ground ) , the data collected from the slides located at 50 and 100 cm above the ground were unusable due to sparseness with large variation .\nas deering et al . showed for the airflow surrounding a simulated mushroom , the spores of t. matsutake did not fly at high elevations but instead streamed down along the forest floor .\nthus , we only used the data from the slides set on the ground for the enumeration .\nthe number of spores increased with time but rapidly dropped as the pileus turned over ( on the fifth day ) ; 475 spores / cm on the first day , 497 spores / cm on the second day , 599 spores / cm on the third day and 836 spores / cm on the fourth day after the veils of pileus opened . ogawa noted that the most abundant time for spore production is 3~4 days after the veil of pileus is torn down .\nhe noted that spores are immature if the veil is not torn down or the pileus turned over , and the amount of spores also becomes smaller .\nthus , we used the cumulative numbers of spores over 4 days to compare the differences in the amount of spores among directions and/or distances .\nthe spores dispersed more along the slope compared to those within the slope ( table 1 ) .\nalthough we did not measure the intensity of the wind within the forest , the intensity of the wind was stronger along the slope than that within the slope .\nthus , we estimated that the difference in intensity of the wind resulted in the differences in spore dispersion .\nthe number of spores dispersed downward was about 1.5 times greater than that dispersed upward , which indicates that gravity was another key factor in the dispersion of spores , as noted by deering et al . .\nalthough spores may usually spread more toward the lower part of mountains , pine mushrooms are mainly produced on the upper parts .\nthis implies that the decline in the productivity of pine mushroom was not due to an insufficient number of spores but actually other factors , such as unsuitable site conditions for growth .\nfurther , the number of spores decreased exponentially as the distance increased from each fruiting body ( fig .\n1 ) . more than 95% of the spores dropped within a meter of the fruiting body , with about 75% of them within 0.5 m ( table 2 ) . however , the spores dispersed over 5 m from the fruiting body could not be discounted as they numbered more than 50 million , considering that the number of spores produced by a fruiting body is about 5 billion .\nthe pattern of spore dispersion was also dependent upon the stand density and other micro - environmental factors ( table 3 ) .\nas stand density increased , the number of dropped spores on the sampled slides decreased ( 2,605 spores / cm for dense , 2,089 spores / cm for middle and 1,670 spores / cm for sparse ) , which indicates that stand density might have affected air flow and therefore spore dispersion .\nogawa reported that spore dispersion is largely dependent upon the climatic conditions or fructification time .\nhe mentioned that the amount of mature spores would be quite few if the air temperature is very high or low .\nin addition , he stated that relative humidity is a key factor in spore dispersion ; for example , colonized spores are high in number after rain or fog . in some cases ,\na spore print was formed on the surface of litter , which indicates that the spores were not widely spread out .\nthus , stand density and other site factors could be major factors in the dispersal of spores , but microclimatic factors such as wind are more important in spore dispersion .\nthe fruiting bodies used for spore counting were 230 22 g in fresh weight , 12 0.3 cm in pileus diameter , 15 0.3 cm in stipe length and 3.5 0.1 cm in stipe diameter .\nalthough the fruiting bodies were relatively larger and heavier than generally harvested mushrooms as goods , they could be considered as representative fruiting bodies of overmatured mushrooms .\nthe spores collected from each fruiting body reached about 150 mg in total mass and were counted as 4.5~5 billion , which varied depending on the size of the mushroom .\nalthough we set the slide glasses at three heights ( 0 , 50 and 100 cm above the ground ) , the data collected from the slides located at 50 and 100 cm above the ground were unusable due to sparseness with large variation .\nas deering et al . showed for the airflow surrounding a simulated mushroom , the spores of t. matsutake did not fly at high elevations but instead streamed down along the forest floor .\nthus , we only used the data from the slides set on the ground for the enumeration .\nthe number of spores increased with time but rapidly dropped as the pileus turned over ( on the fifth day ) ; 475 spores / cm on the first day , 497 spores / cm on the second day , 599 spores / cm on the third day and 836 spores / cm on the fourth day after the veils of pileus opened . ogawa noted that the most abundant time for spore production is 3~4 days after the veil of pileus is torn down .\nhe noted that spores are immature if the veil is not torn down or the pileus turned over , and the amount of spores also becomes smaller .\nthus , we used the cumulative numbers of spores over 4 days to compare the differences in the amount of spores among directions and/or distances .\nthe spores dispersed more along the slope compared to those within the slope ( table 1 ) .\nalthough we did not measure the intensity of the wind within the forest , the intensity of the wind was stronger along the slope than that within the slope .\nthus , we estimated that the difference in intensity of the wind resulted in the differences in spore dispersion .\nthe number of spores dispersed downward was about 1.5 times greater than that dispersed upward , which indicates that gravity was another key factor in the dispersion of spores , as noted by deering et al . .\nalthough spores may usually spread more toward the lower part of mountains , pine mushrooms are mainly produced on the upper parts .\nthis implies that the decline in the productivity of pine mushroom was not due to an insufficient number of spores but actually other factors , such as unsuitable site conditions for growth .\nfurther , the number of spores decreased exponentially as the distance increased from each fruiting body ( fig .\n1 ) . more than 95% of the spores dropped within a meter of the fruiting body , with about 75% of them within 0.5 m\nhowever , the spores dispersed over 5 m from the fruiting body could not be discounted as they numbered more than 50 million , considering that the number of spores produced by a fruiting body is about 5 billion . the pattern of spore dispersion was also dependent upon the stand density and other micro - environmental factors ( table 3 ) .\nas stand density increased , the number of dropped spores on the sampled slides decreased ( 2,605 spores / cm for dense , 2,089 spores / cm for middle and 1,670 spores / cm for sparse ) , which indicates that stand density might have affected air flow and therefore spore dispersion .\nogawa reported that spore dispersion is largely dependent upon the climatic conditions or fructification time .\nhe mentioned that the amount of mature spores would be quite few if the air temperature is very high or low .\nin addition , he stated that relative humidity is a key factor in spore dispersion ; for example , colonized spores are high in number after rain or fog . in some cases ,\na spore print was formed on the surface of litter , which indicates that the spores were not widely spread out .\nthus , stand density and other site factors could be major factors in the dispersal of spores , but microclimatic factors such as wind are more important in spore dispersion .", "answer": "the spore of tricholoma matsutake is considered to be the starting point of the mushroom growth cycle , but the mechanism of mycelial development from the spore stage is not yet clarified . in this study , we tried to measure how far the spores of t. matsutake disperse from a fruiting body located at a pinus densiflora stand in korea . \n we established 16 slide glasses coated with glycerin near a fruiting body in four directions separated by four different distance intervals within a mushroom productive stand after removing all other fruiting bodies from three plots . \n the number of dispersed spores increased with time from the first day ( 475 spores / cm2 ) to the fourth day ( 836 spores / cm2 ) after the pileus opened . \n the number of spores dispersed downward was about 1.5 times greater than that dispersed toward the ridge . \n the number of dispersed spores decreased exponentially as the distance from each fruiting body increased . \n more than 95% of the spores dropped within a meter from the fruiting body , with 75% dropping within 0.5 m. even so , the number of spores dispersed over 5 m from the fruiting body was more than 50 million when considering the total number of spores produced by a fruiting body is about 5 billion .", "id": 238} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngranuloma faciale ( gf ) is an uncommon , benign , inflammatory skin disorder of unknown etiology .\nit is characterized by single or multiple , grey - brown or violaceous nodules or plaques primarily occurring on the face and occasionally at extra - facial sites .\nthe disease is notoriously resistant to therapies and often tends to relapse when treatment is discontinued .\nwe present a patient with multiple lesions of gf and its response to topical tacrolimus .\na 35-year - old female presented to our department with a 5 year history of single , asymptomatic , grey - brown pigmented , nodule over the left cheek [ figure 1 ] .\nit started as a pin head sized papule which gradually increased to 2.5 cm 1.5 cm in size .\ntwo years later similar lesions appeared on the forehead , both arms and upper back .\npast and personal history was unremarkable . before treatment single , grey - brown nodule with prominent follicular orifices over left cheek .\nafter treatment residual lesion after three months of tacrolimus application general physical and systemic examination was normal .\ncutaneous examination revealed multiple , well - defined , grey - brown , indurated , non - tender plaques , varying in size from 0.5 cm 0.5 cm to 1.5 cm 2.5 cm , present on the left cheek , left forehead , both arms and upper back .\nmultiple grey - brown plaques over upper back routine hematological and biochemical investigations were normal .\nskin biopsy ( 4 mm ) from plaque revealed normal epidermis with clear sub epidermal \ngrenz zone and pan dermal dense infiltrate comprising of neutrophils , lymphocytes , histiocytes and plasma cells .\nsmall dermal vessels showed infiltration of neutrophils in the vessel wall along with peri - appendageal and peri - neural infiltrate in subcutaneous fat [ figure 3 ] .\n( h and e , 100 ) skin biopsy with normal epidermis and dense , mixed inflammatoey infiltrate beneath a narrow grenz zone in the dermis .\ninfiltrate is composed of mononuclear cells with neutrophils and eosinophils she was started on intralesional triamcilone acetonide 10 mg / ml injection monthly with tab .\nsix sessions of cryotherapy were performed once monthly after which she developed erythema and itching over the plaques and discontinued treatment .\nthe lesions showed 40 - 50% improvement after 3 months of therapy [ figure 1 ] .\nclassically , red - brown or violaceous nodules or plaques with associated telangiectasia and follicular accentuation are seen on the face over sun - exposed sites .\ndifferential diagnosis includes lupus pernio , lupus vulgaris , lymphoma , discoid lupus erythematosus and deep mycotic infection .\nskin biopsy is characterized by a mixed inflammatory infiltrate with a predominance of neutrophils and eosinophils in the dermis , in conjunction with small vessel vasculitis .\nthere is a grenz zone that separates the infiltrate from the epidermis and pilosebaceous units .\nthe disease is notoriously resistant to therapies and often tends to relapse once the treatment is discontinued .\nseveral medical and surgical modalities like topical and intralesional corticosteroids , cryotherapy , pulsed dye laser , puva , systemic corticosteroids , dapsone and antimalarials have been tried with variable success rates .\ncarbon dioxide laser has also been used in a case of recurrent gf . surgical excision has been performed with often unsatisfactory results .\nablative procedures may leave residual pigmentation and scarring , whereas long - term application of corticosteroids is associated with skin atrophy , telangiectasia and other possible adverse effects . in recent years successes with topical calcineurin inhibitors has been reported .\nseveral authors have reported complete or near - complete resolution of lesions after application of topical tacrolimus 0.1% ointment.[48 ] treatment regimens , duration and time to resolution of lesions have varied in these case reports [ table 1 ] .\nothers have found time to resolution to be between 4 and 6 months . in our patient ,\ntreatment with tacrolimus 0.1% ointment twice daily for 3 months has resulted in improvement . reported cases of successful treatment of granuloma faciale ( gf ) with topical tacrolimus tacrolimus\ninhibits t - cell proliferation , production and release of several pro - inflammatory cytokines like interleukin-2 ( il-2 ) , il-4 , tumor necrosis factor - alpha , and interferon - gamma ( ifn - gamma ) .\nalthough the pathogenesis is still unknown , it has been suggested that gf may be an ifn - gamma mediated disease .\nin addition , an increased production of il-5 , probably induced by the clonal expansion of a locally recruited t - cell population may enhance the attraction of eosinophils into the lesions of gf .\ntherefore , a possible mechanism of action of topical tacrolimus in this condition may be the inhibition of ifn - gamma and il-5 production and release , induced by the down - regulation of the t - cell activity , primarily involving the calcineurin binding and inactivation .\nhowever , we did observe eosinophils in skin biopsy in our case , probably since the biopsy was taken after one year of oral dapsone .\nour patient experienced a relevant improvement within 3 months of treatment with tacrolimus ointment after no response with intra lesional steroids , dapsone and cryo therapy . in conclusion\n, the previous reports and our observation suggest that topical tacrolimus may be a well - tolerated , efficacious therapy for gf .", "answer": "granuloma faciale ( gf ) is a chronic condition characterized by red - brown plaques with follicular accentuation present usually on the face . \n we present a case of 35-year - old female with 5 year history of plaques over cheek and extra facial sites consistent with gf and its response to topical tacrolimus . \n this case supports previous reports of successful treatment of gf with topical tacrolimus .", "id": 239} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin 2008 , the greater london authority and the london health consortium , with funding provided by the big lottery , instigated a series of health interventions entitled \nwell london. these activities were set up in 20 of london 's most disadvantaged neighbourhoods , in an effort to promote healthier life - styles as a way of combating chronic disease ( wall et al .\nan evaluation of the project was undertaken in which a series of in - depth interviews were conducted with 60 residents across three of the well london areas ; a key component of the interview was to enquire about the environment and residents perceptions of their neighbourhood . a frequent and vociferous complaint that arose unprompted concerned the prevalence of dog excrement , or to use local terminology : \ndog poo. not only was the frequency of the complaint remarkable , but also its specificity and distinctive nature , making further detailed investigation necessary .\napart from an element of antipathy , there was also considerable anger expressed in relation to : who was responsible ; the lack of care demonstrated by its ongoing presence ; and fear over its risk to human health .\n dog - poo was not the only form of pollution complained about in the three areas , but it was the most frequently cited . in terms of risk to human health ,\nfor example , since 2000 between one and eight laboratory confirmed reports of toxocarosis have been received annually by the health protection agency ( hpa 2011 ) .\nin addition , a keep britain tidy report into litter cites a 40% drop in the incidence of dog faeces in the uk over recent years ( 2007 ) . despite this lack of evidence concerning risk or prevalence , canine faeces\ncontinues to be a significant cause for complaint , requiring further explication in order to understand its relevance for public health . in a study of urban environmental factors that impact on health ,\nkennedy ( 2000 ) cites residents complaints of dog faeces as a blight that affected their sense of wellbeing .\nsimilarly , two separate studies by jones ( 1996 ) and cresswell ( 1992 ) report residents complaints of dog faeces in urban areas of the uk affected by poverty and environmental neglect .\ntherefore , the presence of dog faeces has associations and implications that can be linked with more subjective responses\n. one key facet of the complaints raised by residents in the well london study was a sense of disgust evoked by \ntherefore , the challenge was to explore not the grievance itself ( whether dog poo existed or its potential as a disease carrying agent ) but rather the symbolic \nthis article critically engages with residents explicitly focused disgust with canine faecal matter and generates understanding of its symbolic value that helps clarify what has to date , been a poorly resolved public health issue .\nsixty qualitative interviews were conducted in total : 20 individuals in each of the three well london areas , which were located in the north , east and south of the city .\nall three areas were characterised by high levels of unemployment , poor health , environmental neglect and a mixed indigenous and global migrant population .\nquality assurance procedures were undertaken whereby three randomly selected interviews were recoded , blind to the initial coding , by two independent researchers .\nthe three versions of each interview were then compared to identify new codes and establish the degree of consensus in applying a particular code to similar text . a major part of the interview focused on what residents thought about the area where they lived\n. recurrent and spontaneous reference was made to the prevalence of dog faeces in the area and , more subjectively , the feelings that were evoked by its presence .\ndog poo ( most frequently cited among all its synonyms ) , over all other complaints . extended coding of the interviews revealed the contextual significance of these complaints . \nincivility emerged as a recurrent theme : a lack of respect for the neighbourhood environment by residents and negligence by local authorities whether the police or local council .\nthis meant carrying out repairs , cleaning and ensuring personal safety , especially in relation to the presence of gangs , local drug dealers and other types of criminality .\nfurther , measurement of actual incidence of dog foul across london was undertaken : 40 areas were examined and divided into \n211 were found to contain no dog faeces ; 72 had a small amount and eight had a moderate amount .\nhowever , 117 coded references pertaining to dog poo ( and its synonyms : dog shit / muck / litter / mess / fouling ) were found in all 60 interviews .\nthe disparity between high numbers of complaints and the limited presence of actual faecal matter required an alternative mode of analysis that would help locate , more specifically , residents concerns . interpreting how meaning is expressed through cultural symbols in this instance \nanalysing the symbolic content and context in which the complaints occurred , highlighted compelling evidence of its link to social neglect , including criminality , dirt and the absence of cohesive community relations .\nthe work of social anthropologist douglas ( 1966 ) is seminal in the symbolic interpretation of matters pertaining to pollution .\nalso , studies by van der geest ( 1998 , 2007 , 2008 ) , stallybrass and white ( 1986 ) , laporte ( 2000 ) , enzensberger ( 1972 ) and miller ( 1997 ) offer useful theoretical perspectives on dirt and disgust ; especially regarding bodily substances that transgress boundaries in relation to social morality , inequality and taboo .\nthe inherent value of examining cultural symbols shows how in this instance , they express not only fears of the transgression of boundaries , but also how \ndog poo is constructed as a metonym for the disgust felt by residents about their experience of incivility .\nthis includes neglect of the environment , and a lack of respect by local authorities and fellow neighbours alike , as one resident implied : and the worst thing is they just , they poo everywhere in the buildings a month back there was dog poo in our own building .\ni do n't know whose poo it is whether it 's human or dog poo , but i seen it. another described a similar sense of repulsion : the outside spaces , there 's dog foul .\ni mean wherever you put your feet and it 's unsafe because the poo of the dog and you put your foot \noh no! the focus on canine excrement did not exclude other complaints : of drugs , gangs , noisy neighbours and the lack of intervention by either police or local authorities .\nhowever , complaining about dog poo conveyed a powerful message about these neighbourhoods blighted by multiple problems , and often by unknown perpetrators : like this drug dealing problem going on , on my doorstep .\nyou do n't know who 's done it , or why they done it , or where did they come from .\nand they 're smoking , they 've got needles there on the stairs , they wee do on the stairs , everything we ca n't say nothing . and my lift is still broken .\n( sita ) the notion of incivility evoked through residents descriptions of their environment determined the appropriateness of symbolically linking complaints of dog poo , with the experiences of social neglect .\nas requests to improve living conditions and expressed worries about safety and cleanliness were ignored , a pervasive sense of hopelessness took over .\nright , the area is dangerous , dirty , very , very unkempt and has been basically forgotten by the powers that be for the past , i 'd say , 15 years . in as much as one person who i spoke to at the local housing office who was at the time in charge of major works , did n't even know where i was living . did n't know where it was , so that 's the \nit 's just been a forgotten little area and it 's been left to rot and decay .\n( robert ) for stallybrass and white : what is socially peripheral , is so frequently symbolically central ( 1986 : 5 , authors italics ) .\nthis resonates with the well london residents sense of social marginalisation that was marked by the absence of effective management of the neighbourhood , as explicitly articulated above .\nbut , when these explicit complaints were neither heard nor acted upon , they became symbolically represented by excreta , which defined their experience of marginality .\nthe path as you go up there , there 's always glass up there or dogs poo , always \nthere 's dogs poo along there and it 's , well , it 's just disgusting. van der geest ( 1998 , 2007 , 2008 ) has written extensively on attitudes towards defecation , including an historical examination of the origins of our revulsion towards bodily functions and their \nmanagement. he suggests that without the containment of bodily matter , there is nothing to prevent chaos and disorder ( 2007 ) .\ntherefore , if faeces , animal or human , is taken as an effective metonym that represents disorder , it follows that managing dirt has as its main function the restoration of order primarily , social order as part of a civilising process .\ndirt in its rightful place ordered and bounded within a set of social rules of behaviour .\ndouglas ' ( 1966 ) work on symbolism and in particular matter out of place , states that \ndirt is defined by its place or context ; in other words , where it is found and who is responsible for it .\nfor example , faecal matter inside the body is less problematic than when it becomes external to it , where it is an object of revulsion .\nthe attitude and management of excrement , both human and animal , is linked with the state as it intervenes in the management and consequent attitudes towards dirt ; segregation of public and private means that all faecal matter is consigned to private rather than public space ( enzensberger 1972 , laporte 2000 ) .\nfaeces , now considered taboo in the public domain , contrasts with the pre - victorian era when horse manure covered the streets of london and running sewers were open to public senses ( pike 2005 ) .\nthis segregation of public and private in relation to cleanliness was also acknowledged among residents : when we moved to this area , we saw dog poo now it 's a little bit clean , my area is , because it 's a private area. another spoke of her annoyance at her neighbour who \npushed rubbish over to her side of the passageway , invading her private space and breaking boundaries .\nbut , complaints also illustrated a more extreme form : the permeability of private space that could be infiltrated by bad smells and noise : yeah , the noise .\nmy downstairs neighbours , they 're singing like five o'clock in the morning and it wakes you up and you just ca n't do anything .\nand then they smoke marijuana and you know this is a converted building ? so there 's lots of holes in the you see those things ?\nyeah , every time they smoke , every time they drink if they 're vomiting in their toilet , it all comes up ( here ) .\ndog poo has salience within their particular social and cultural milieu of urbanised , inner city london where neighbourhoods are unsafe , environmentally polluted and often without social cohesion .\nanger and blame is placed on those who seem to ignore the boundaries i.e dog owners , \ndirty neighbours , the police , or the local authorities responsible for the management of the neighbourhood .\n dog poo is therefore a transgression of not only spatial boundaries , but also social norms of what is considered civil behaviour ; especially when focused on personal responsibility : and that 's one thing as well , the dog fouling , they do n't pick up .\nthey do n't pick up their dog fouling , do you know what i mean ? and\ni 'll tell you what , it would be a big sense of achievement if they actually put cameras in every direction to catch these people out , because it 's terrible . you 've got kids playing around and every time they 're playing football , they stop in dog foul .\nas campkin and cox ( 2007 ) suggest theorising about dirt is constitutive of space and social relations. here , vociferous complaints of canine faeces in the absence of actual evidence of high incidence indicated a more hidden form of distress or grievance that was better understood by examining its symbolic content , as well as its context . by taking \ndog poo as a metonym for the disgust with which residents experienced their neighbourhoods , the authorities and each other it was possible to gain deeper insight into the problem .\nacknowledgement of this has implications for intractable public health problems , where not only the contextualisation of complaints is important , but also analysis of their deeper symbolic components ; especially in the face of frequent , inexplicable complaints .\nconducting such an analysis uncovered the distress of residents living in some of london 's more deprived neighbourhoods where grievances were frequently ignored , leading to frustration and anger . had the issue of dog faeces\nclean up operation alone , this would never have uncovered the scale of the problem or the depth of feeling in relation to the issues , which can be defined as poor social relations and inadequate or ineffective communication with local authorities .\ninvestigations and analyses of this kind lend themselves to the development of constructive , inclusive public health policies that can improve the wellbeing of marginalised populations by understanding how people articulate their concerns .\nthe approach used here is effective in this , because it can : generate new insights into intractable public health problems ; offer alternative and useful methods to understand and communicate complex social issues in relation to public health ; advance theoretical knowledge ; and broaden the scope of analytic tools with which to understand well - being and society .", "answer": "during a well london study , residents were asked about their neighbourhood and its environment . above all other complaints , \n dog poo was mentioned as a key concern . despite low rates of infection and disease among the human population resulting from contact with canine faecal matter \n , the concerns of the public continue to rate it as a serious public health issue . \n most public health studies , therefore , seek to identify processes of transmission and disease pathology as a method of addressing the problem . \n this study approaches the issue through a contextualised analysis of residents complaints , using anthropological theory to examine the symbolic representation of \n dog poo. analysis of the interviews shows that these specific complaints were located among less easily defined or articulated experiences of social and environmental neglect , where neighbours were estranged from one another and local authorities seen as negligent . \n this approach has important implications for public health , as it provides not only a strong indicator of the level of dissatisfaction within some of london 's more disadvantaged neighbourhoods , but also identifies a need for policies that are grounded in cross - disciplinary research into the relationship between health , wellbeing and experiences of marginalisation among urban populations .", "id": 240} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwritten informed consent was obtained from the parents , and assent was obtained from the subjects .\nthe institutional review board at ut southwestern medical center approved this study , which began in august 2006 and ended in may 2008 .\nparticipants were randomized to either the mi or sde group based on a sex - stratified schedule .\na third education session was planned ( t2 ) if a1c continued to be 9% .\nthree diabetes educators were assigned to the mi arm and trained on motivational interviewing at a 2-day workshop .\n( 3 ) , journal articles ( 4 ) , and guidance from the mi trainer and psychologist .\nthe remaining six educators were assigned to the sde arm and did not receive additional training .\neducators used a comprehensive checklist compiled using core content recommended by the american diabetes association ( ada ) on medication , monitoring , acute complications , and lifestyle ( 5 ) .\nall audiotapes were coded using the motivational interviewing treatment integrity 3.0 ( miti 3.0 ) coding system ( 6 ) .\nthe coder attended a 2-day workshop on miti 3.0 and was blinded to the treatment groups .\na1c ( measured via a dca vantage analyzer ) and psychosocial measures were collected at baseline and at 3 , 6 , and 9 months ( t3 ) .\npsychosocial measures included the center for epidemiologic studies depression scale ( ces - d ) ( 7 ) , the epidemiology of diabetes interventions and complications quality of life questionnaire ( edic - qol ) ( 8) , and the summary of diabetes self - care activities ( 9 ) .\nthe mixed - model procedures of proc mixed in sas version 9.2 ( sas institute , cary , nc ) were used for the primary analysis .\nbaseline values of a1c and each baseline psychological measure were included as covariates in the respective analyses .\nthe main effect of treatment group and the treatment group time period interaction effect were examined .\ncohen 's d was interpreted as the effect size estimator for the between - subject treatment group effect .\na1c ( measured via a dca vantage analyzer ) and psychosocial measures were collected at baseline and at 3 , 6 , and 9 months ( t3 ) .\npsychosocial measures included the center for epidemiologic studies depression scale ( ces - d ) ( 7 ) , the epidemiology of diabetes interventions and complications quality of life questionnaire ( edic - qol ) ( 8) , and the summary of diabetes self - care activities ( 9 ) .\nthe mixed - model procedures of proc mixed in sas version 9.2 ( sas institute , cary , nc ) were used for the primary analysis .\nbaseline values of a1c and each baseline psychological measure were included as covariates in the respective analyses .\nthe main effect of treatment group and the treatment group time period interaction effect were examined .\ncohen 's d was interpreted as the effect size estimator for the between - subject treatment group effect .\na total of 26 participants were randomized to the mi group and 28 to the sde group .\nsix - month data ( t2 ) were available on 21 and 23 patients in the mi and sde groups , respectively ( table 1 ) .\nfour patients each in the mi and sde groups had a third education session at t2 .\nbaseline characteristics , a1c , psychosocial measures , and miti 3.0 least squares ( ls ) means are adjusted for each respective baseline measure .\nf statistic was used to test for omnibus mean difference on each measure between the two treatment groups over 6 months of follow - up . * children 's health insurance program ( chip)/children with special health care needs ( chscn ) .\nprimary outcome variable , least squares means for a1c , adjusted for baseline over 6 months of follow - up .\noverall competence of the clinician in using mi based on a global rating scale of 15 , where 1 is low spirit and 5 is high spirit .\nthe score for beginning proficiency and competency are 3.5 and 4 , respectively . # giving information , education , providing opinion without advising .\nfidelity to mi would correspond to lower scores on this variable . * * asking permission before giving advice , affirming , emphasizing control , and supporting the participant . number is based on frequency of occurrences .\nfidelity to mi would correspond to higher scores on this variable . after adjusting for baseline a1c , the pattern of omnibus least squares ( ls ) mean a1c values differed between groups ( f = 4.84 , df = 1 , 42.1 , p = 0.03 ) over the 6 months of follow - up ; the sde group had lower a1c ( least squares mean 10.31 , se 0.32 ) than the mi group ( least squares mean 11.35 , se 0.34 ) ( d = 0.66 , medium effect size ) .\nno overall time period effect emerged ( f = 0.33 , df = 2 , 34.8 , p = 0.72 ) and no treatment group time interaction effect was found ( f = 0.20 , df = 2 , 34.8 , p = 0.81 ) ( table 1 ) . after controlling for baseline , there were no differences between the groups on any psychosocial outcome , none of which improved in either group ( table 1 ) .\nthere were 21 subjects in the mi group and 22 in the sde group with interpretable tapes and miti scores .\nthe groups differed on all indicators of fidelity to mi in the expected direction ( p < 0.001 , repeated - measures anova ) ( table 1 ) .\nafter adjusting for baseline a1c , the pattern of omnibus least squares ( ls ) mean a1c values differed between groups ( f = 4.84 , df = 1 , 42.1 , p = 0.03 ) over the 6 months of follow - up ; the sde group had lower a1c ( least squares mean 10.31 , se 0.32 ) than the mi group ( least squares mean 11.35 , se 0.34 ) ( d = 0.66 , medium effect size ) .\nno overall time period effect emerged ( f = 0.33 , df = 2 , 34.8 , p = 0.72 ) and no treatment group time interaction effect was found ( f = 0.20 , df = 2 , 34.8 , p = 0.81 ) ( table 1 ) .\nafter controlling for baseline , there were no differences between the groups on any psychosocial outcome , none of which improved in either group ( table 1 ) .\nthere were 21 subjects in the mi group and 22 in the sde group with interpretable tapes and miti scores .\nthe groups differed on all indicators of fidelity to mi in the expected direction ( p < 0.001 , repeated - measures anova ) ( table 1 ) .\nalthough we hypothesized that lack of motivation more than poor knowledge impedes good metabolic control , we found that one brief intervention followed by a short education session could decrease mean a1c levels by 1% .\nsubsequent sessions did not further affect the a1c , and the positive effect was maintained at 9 months .\nwe should have assessed knowledge of diabetes pre- and posteducation to show that improved knowledge played a role in our results .\nhowever , we did find a higher amount of given information in the sde group compared with the mi group by miti scoring .\nthe lack of efficacy of mi in our study is consistent with a recent trial in adult patients with poorly controlled type 1 diabetes ( 10 ) .\nin contrast , mi improved both metabolic control and psychosocial measures over a 12-month period in teens with diabetes ( 11 ) , but this study had more interventions over a longer period than ours .\nthis was a small study that detected a treatment effect in the direction opposite to that hypothesized .\nperhaps the educators in the mi group were not proficient in mi compared with other studies ( 1113 ) , but the miti demonstrated good fidelity of our intervention to mi principles . in conclusion , brief motivational interviewing - based counseling with no pre - established level of educational content does not lead to improved metabolic control , whereas ongoing education is important for teens with poorly controlled diabetes .\nwe did show that we could train diabetes educators in mi with adequate proficiency . before translating research to clinical practice\nfuture studies should compare structured diabetes education and sde plus motivation in a multicenter setting for a longer follow - up period .", "answer": "objectiveto compare motivational interviewing based education ( mi ) and structured diabetes education ( sde ) for improving a1c and psychosocial measures in adolescents with type 1 diabetes.research design and \n methodsthis study was a 9-month randomized controlled trial comparing mi ( n = 21 ) to sde ( n = 23 ) . \n interventions were at baseline ( t0 ) and 3 months ( t1 ) , with a1c and psychosocial measures obtained at 6 months ( t2 ) and 9 months ( t3).resultsover the 6 months of follow - up , the sde group had lower adjusted mean a1c value ( least squares mean 10.31 , se 0.32 ) than the mi group ( least squares mean 11.35 , se 0.34 ) ( p = 0.03 , d = 0.66 ) . there were no differences on any of the psychosocial measures.conclusionssde is effective at improving metabolic control in adolescents with type 1 diabetes . \n diabetes educators were proficient in learning mi .", "id": 241} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nintractable nausea and vomiting are very rare symptoms of medullary compression and there are approximately less than 10 cases reported in the literature of the aforementioned symptomatology mostly due to tumors .\nthere is one reported case where vertebral artery compression of the medulla led to intractable nausea and vomiting .\na 69-year - old woman presented with a 10-month history of intractable nausea and vomiting resulting in a 50 pound weight loss .\nshe had an extensive medical workup at multiple outside hospitals including a comprehensive gastrointestinal workup which was significant for celiac disease .\nher pertinent past medical history includes a history of breast cancer , mastectomy , and cholecystectomy . during her evaluation by the gastroenterologists at our hospital ,\nthe diagnosis of celiac disease was confirmed , and she was also noted to have a duodenal ulcer .\nhematologic and biochemical workup was only significant for anemia attributable to her ulcer and celiac disease .\nmagnetic resonance imaging / angiography ( mri / mra ) of the brain and neck , and diagnostic four vessels cerebral angiogram were obtained to further evaluate her dizziness and double vision .\nthe left vertebral artery angiogram revealed a tortuous left vertebral artery with a 9.6 5.6 mm dissecting aneurysm in the v3 segment .\nthis , along with dolichoectasia of the vertebro - basilar arteries , resulted in compression of the medulla oblongata , which was also confirmed in the contrasted mri / mra of the brain and neck [ figure 1 ] . computed tomography angiography ( cta ) also confirmed that the vertebral artery was pushing the medulla medially [ figure 2 ] .\nthe patient was offered a microvascular decompression ( mvd ) of the vertebral artery to attempt to decompress the brainstem and alleviate her intractable nausea and vomiting .\npreoperative magnetic resonance imaging ( mri ) t2 sequenceshowing compression of the medulla by the vertebral artery preoperative computed tomography angiography ( cta ) showing a tortuous left vertebral artery crossing the midline a left retrosigmoid craniotomy was completed to approach the vertebral artery and lower brainstem . the elongated , ectatic vertebral artery\nadditionally , indentation of the lower part of the medulla by the vertebral artery was also recognized .\napericranial graft was used as a sling and tacked to the dura , to decompress the brainstem .\nthe postoperative course was uneventful , and the patient was kept in the hospital to transition her from gastrostomy tube feedings to regular oral feeding .\npostoperative cta demonstrated that the vertebral artery had been mobilized [ figure 3 ] away from the medulla .\npostoperative cta showing left vertebral artery away from the medulla the patient was discharged from the hospital without any antiemetic medication and was documented to have started gaining weight . at her 2-year postoperative visit , the patient had a nonfocal neurologic exam without recurrence of her prior nausea or vomiting .\npatients with central lesions often wait months or years and undergo countless tests before a central etiology is added to the differential diagnosis because most cases do not present with localizing neurological deficits\n. sustained hiccups with vomiting or isolated spontaneous vomiting with negative gastrointestinal symptoms should prompt further workup , including neuroimaging , to search for a central cause .\nthe patient in our case was incidentally found to have dizziness and diplopia during the initial workup , but was not demonstrating positional vomiting or headaches , which would have prompted a neurological workup sooner . the tortuous vertebral artery in this case\nwas found on the diagnostic mri / mra of the head and neck obtained secondary to her history of breast cancer and new onset symptoms of diplopia and dizziness . without a proper neurological examination\nthis patient 's celiac disease and gastrointestinal reflux would have continued to mask the true cause of her symptoms . while compression of the medulla by a dilated vertebral artery is much less common than other brainstem compression syndromes such as trigeminal and glossopharyngeal neuralgias ; it is still significant .\nvascular compression of the medulla can cause disabling positional vertigo , hypertension , and hemifacial spasm ; but there are only a few reports of intractable nausea and vomiting as a symptom of an ectatic vertebral artery .\nless than 10 cases of nausea and vomiting due to vertebral artery compression have been reported in the literature .\nof the 20 cases of vertebral artery compression of the medulla reported in a meta - analysis by savitz et al .\n, only one patient experienced nausea and vomiting as a symptom . the majority of patients presented with hemiparesis and cranial nerve dysfunction .\nmvd was the choice of treatment for 17 of the patients , including the patient with symptoms of nausea , and it was shown to relieve symptoms in 16 patients .\nmedullary compression can produce a wide spectrum of signs and symptoms from very few to several .\nregardless of the etiology , compressive forces on the neuronal tracts and nuclei that lie within the medulla can produce a number of clinical scenarios .\nwhen the etiology is vascular in origin , ischemic injury can produce symptoms such as headache , transient ischemic attacks ( tias ) , or infracts depending on the location of the compression . at the floor of the rhomboid fossa\nit contains specialized cells consisting of ependymal cells and tanycytes that allow for direct communication of cerebro spinal fluid and blood because it lacks an intact blood brain barrier . as a circumventricular organ ,\nthe area postrema is able to detect toxins and drugs in the blood as well as hormones and other humoral signals to help maintain autonomic homeostasis .\nstimulation of the area postrema by vagal afferents from the nucleus ambiguous and gastrointestinal system or from emetogenic drugs and cytokines in the blood may trigger vomiting .\nthe nucleus tractus solitarius ( nts ) lies adjacent to the area postrema , serves as a relay center to collect all afferent signals and activate the appropriate visceral nuclei to coordinate the action of vomiting .\nefferent pathways from the area postrema and nts project to the central pattern generator , ventral medulla , and hypothalamus .\nthe central pattern generator is proposed to coordinate the activation of these nuclei within the medulla .\nthe efferent signals stimulate the appropriate parasympathetic and sympathetic neurons , which produce the different phases of vomiting .\nthe signal also diffuses through the brain via microglial messengers and cytokines such as substance p to allow for the cognitive recognition of emesis . a lesion to any of the afferent relay tracts or emetic reflex center proper may produce an abnormal emetic reflex and could produce intractable nausea and vomiting , as was observed in our case . on the preoperative mri ,\nthe vertebral artery was seen to be compressing the medulla , where the area postrema is located , and nts at the inferior and posterior limit of the fourth ventricle .\nthe potential disruption of the area postrema in this case may have caused an overstimulation of the emetic reflex .\nthe first mvd was performed in 1966 by dr peter jannetta to relieve the facial pain in a patient with a compressed trigeminal nerve .\nit is now used to treat compression of the facial and glossopharyngeal nerves , as well as vascular abnormalities .\nthe indications of mvd could potentially be expanded to treat compressive symptomology ; including , for example , intractable vomiting due to vascular compression of the medulla as demonstrated in this case report .\nthis case demonstrated the importance of neurological investigations in the isolated intractable vomiting patient without a clear evidence of peripheral cause and including a central nervous system etiology on the differential , and the role of mvd in achieving cure .", "answer": "vertebral artery compressing the medulla and causing intractable vomiting has only been reported once previously . \n we report a case of a 69-year - old woman with intractable nausea and vomiting causing a 50 pound weight loss and who failed medical management and whose symptoms were completely reversed following microvascular decompression ( mvd ) .", "id": 242} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthoracic injury can result in a wide range of clinical manifestations depending on the structures involved like chest wall , diaphragm , mediastinum , trachea , lungs parenchyma etc .\nthe non penetrating trauma to the lungs manifests as contusions , lacerations of pulmonary parenchyma , pneumatocele formation , hematomas , and fractures of trachea and bronchi .\nwhile pulmonary contusion is commonly associated with blunt thoracic trauma , appearance of cavitary lesions variably described as traumatic pulmonary pesudocysts , ( tpp ) , traumatic pneumatoceles , traumatic lung cysts are rare , developing in less than 3% of patients with pulmonary parenchymal injuries .\na 26 year old unmarried male was referred to us with history of left sided chest pain for two days .\nhe had consulted at local hospital immediately after trauma . a skiagram chest taken there [ figure 1 ] showed non homogenous opacity with central lucency in the region of left hilum . on examination ,\nthe patient gave history of trauma - a tractor wheel hitting him on the anterior chest wall , while he was lying down ; following which he developed the pain .\nthere was no history of breathlessness , fever , cough , hemoptysis , cough or expectoration .\nthere was no history suggestive of bronchial asthma or exposure to pets at home or work place .\nthe margins of the lesion were now thinned out and smooth [ figure 2 ] .\nchest radiograph on day 1 - pa view showing non homogenous opacity with central translucency near left hilum day 3 - chest radiograph pa view showing multiple cavities near left hilum his sputum for afb was negative .\nother lab investigation revealed haemoglobin 14.4 , leukocyte count 7900 , and differential count of 78 % polymorphs and 19% lymphocytes .\nhis serum was non reactive for hiv antibodies . a ct scan of thorax done on 03 - 09 - 2011 showed a single smooth walled cavity abutting left chest wall with surrounding areas of ground glass haziness , probably suggestive of lung contusion [ figure 3 ] . computed tomogram of chest showing smooth walled cavity in left upper lobe with surrounding ground glass opacity of lung contusion fibre optic bronchoscopy\nwas performed to achieve a microbiological diagnosis and to inspect the trachea - bronchial tree in view of previous reports being inconclusive .\nbronchoscopy revealed a bleeding spot in left main bronchus , but no active bleeding was seen .\nbronchial brushings taken from left upper lobe were negative for malignant cells and afb , and the lavage fluid also was sterile .\nin view of the patient 's history of ancedent recent trauma , negative past and present history for any infectious process , and negative microbiological reports , a diagnosis of post traumatic pulmonary pseudo cyst ( tpp ) was made .\nserial follow up chest skiagram showed rapid resolution of the cavities [ figure 4 ] without any antibiotics , thus confirming our diagnosis of tpp .\namong the various names given to the cavitary appearance of pulmonary lacerations , the term traumatic pulmonary pseudo cysts ( tpp ) appears to be the best nomenclature because the wall of these lesions are formed by the inter lobar interstitial connective tissue and shows no epithelial lining or bronchial wall elements .\nthe rarity of the entity can be estimated by the fact that there have been only around 10 large case series with 8 or more patients published since 1967 .\ntpp following blunt or non penetrating trauma develops through a mechanism that allows transmission of high compressive forces to the lung parenchyma .\nretraction of normal lung elastic tissue from contusion induced cavities permits the escape of air and fluid into it .\nlaceration of pulmonary parenchyma and appearance of cavity may also occur if there is closure of the glottis at the moment of injury which may prevent fast exit of the air from compressed lung segment .\nthe parenchyma and/or interstitium get lacerated in a bursting manner resulting in a cavity formation .\nresolution of a pulmonary hematoma or drainage into a bronchus may result in development of tpp at a later stage and it is called secondary tpp .\ntpp can occur at any age , but they are more often seen in children and young adults , probably because of greater compliance of chest wall which permits a larger transmission of force of impact to the parenchyma .\nsorsdahl and powell reported that 85% of the patients with tpp were under the age of 30 years with male predominance .\nimpact velocity and degree of chest wall displacement may play an important role in the development of tpp after blunt trauma to the chest .\na high velocity impact causes peripheral tpps while a low velocity high displacement impact produces central parenchymal and major bronchial disruption .\ntpp is a clinical entity that manifests itself with minor clinical and major radiological signs .\nthe usual clinical manifestations include hemoptysis , occurring in about half of the cases , cough , dyspnoea , chest pain , fever and leucocytosis .\ntpps may appear immediately or within a few hours after injury and their sizes range from 2 to 14 cm in diameter tpp can be differentiated from cavitating hematomas on the basis of radiographic appearance of air within the tpp 's within 48 hours .\ntpps may be identifiable on chest radiography but ct scans are superior for detecting them .\nunlike other cystic lesions and cavities , the size , shape , and nature of wall of tpps change relatively quickly . therefore\n, serial skiagrams of chest , done over several days can help to differentiate pseudo cysts from other lesions .\nfound a greater resolution time in blood filled tpps and those with > 2 cm in size .\nthey may be seen on the site of injury or on the opposite side secondary to countre coup effects .\nthe majority of tpps are found in the lower lobes , the ct appearance of single or multiple thin walled cystic lesions with air space consolidation of the surrounding lung parenchyma in the backdrop of antecedent trauma is diagnostic .\ndifferential diagnosis includes ruptured oesophagus , or herniation of viscera , post pneumonia pneumatocele , tuberculosis cavity , cavitating bronchial carcinoma , lung abscess , bronchogenic cysts , and pulmonary sequestration .\na history of trauma , rapid sequential changes over days on chest skiagram , and presence of contusion on the base of lesion usually delineates any confusion . if the cavitary lesion does not decrease with time other aetiology must be considered .\nconservative management is recommended as long as evidence of a decrease in size of the lesion occurs within 6 weeks after trauma in adults and 3 - 4 months in children .\nthe use of antibiotics is controversial and may be used more to provide simple reassurance that the pseudo cyst wo nt get infected .\ntpp 's can be complicated and may require surgery . they may rupture and cause a secondary pneumothorax that may require tube thoracostomy .\nthe indications for diagnostic and therapeutic bronchoscopy are endobronchial bleeding , thick sputum , large air leak , mediastinal emphysema and lobar collapse .\nthe approach to an infected pseudo cyst is similar to that for a lung abscess .\nif an infected pseudo cyst is larger than 2 cm , or there are unremitting signs of sepsis after 72 hours of antibiotics , the pseudo cysts may be drained percutaneously .\nearly lobectomy may be considered for complex tpp 's with extensive lung abscess surrounded by necrotic parenchyma , failure of bronchoscopic treatment of massive airway bleeding , infected pseudo cyst more than 6 cm in size , or no response to more conservative treatment .\nvideo assisted thoracoscopic surgery ( vats ) may be considered for managing a persistent air leak , hemothorax due to pseudo cyst rupture , failure of lung expansion , progressive enlargement of pseudo cyst and compression of lung parenchyma .\nlate thoracotomy has been reported ( lobectomy , cystotomy , capitonnage ) up to 6 months after trauma because of pneumonic infiltration and persistent cavitary size .\nour patient presented with few abrasions on anterior chest wall and history of blunt trauma to chest wall of one day duration .\nthere was no previous history of any respiratory illness or unconsciousness during or after trauma .\nthe immediate chest skiagram revealed an area of consolidation with central area of lucency around left hilar region .\nthere was no associated cough , fever , expectoration , hemoptysis or breathlessness which clinically ruled out an infective process .\nserial skiagrams over next 24 hours showed a rapid development of a cavity which regressed spontaneously and significantly over next 7 days without any antibiotics .\nct thorax done was also suggestive of tpp , in view of a cavity adjacent to anterior chest wall with surrounding contusion .\nexclusion of other infectious diseases like tuberculosis , lung abscess , by absence of relevant clinical history , sputum negativity on zn staining , sterile pyogenic culture , negative mantoux test , negative microbiology of bal , and cytology of bronchial brushing led us to the diagnosis of tpp which was well supported by the available literature .\nit is generally a self limiting benign condition , diagnosed by excluding other conditions which may present with similar radiological manifestations .\na typical history of blunt trauma to chest , rapid radiological changes of the cavity and exclusion of other cavitary pulmonary diseases by adequate laboratory work helps in diagnosing this rare condition .\nthe disease at times might become complicated and becomes life threatening ; hence , should be closely monitored and followed up .", "answer": "blunt thoracic trauma manifests in various ways , depending on the structures injured and type of injury . commonly manifested as parenchymal contusion , at times , pseudacavitation may also been seen on the chest x ray . \n they are to be differentiated from other causes of pulmonary cavitations which are often done based on history . \n the so called pulmonary pseudo cysts usually have a benign course and needs only observation .", "id": 243} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nflurodeoxyglucose ( f - fdg ) positron emission tomography / computed tomography ( pet / ct ) has become the imaging modality of choice for initial staging , follow - up and treatment response assessment in patients with hodgkin 's lymphoma and has proved superior to contrast enhanced ct ( cect ) in these settings .\nf - fdg pet / ct has accuracy of almost 100% in diagnosing primary splenic involvement during initial staging of lymphoma . however , in the post - therapy setting its role for evaluation of secondary splenic involvement is limited .\none of the pattern of splenic activity that help to detect splenic involvement on pet / ct is diffusely increased f - fdg uptake greater than that in the liver and bone marrow with or without corresponding ct lesions . in this context , we report a case of a patient with hodgkin 's lymphoma in remission presenting with f - fdg avid splenomegaly .\nthe present case report is about a 22-year - old male patient who presented with enlarged right cervical lymph node .\nf - fdg pet / cect performed for staging revealed metabolically active lymph nodes on either side of the diaphragm [ figure 1a , broken arrows ] , enlarged spleen with multiple hypodense hypermetabolic , lesions [ figure 1a , arrow ] ( suvmax= 9.4 ; spleen suvmax / liver suvmax ratio = 3.76 ) and bone lesion .\nhe was then given 6 cycles of chemotherapy and f - fdg pet / cect was done for response evaluation .\npet / ct showed complete metabolic response , with normal spleen uptake [ figure 1b , arrow ] ( spleen suvmax= 2.5 , liver suvmax= 2.6 s / l ratio = 0.96 ) . at 1-year\nlater routine follow - up the patient complained of mild fever , lethargy and listlessness . in view of previous history of hodgkin 's lymphoma ,\npet / ct revealed enlarged spleen with diffusely increased fdg uptake [ figure 2a c , arrow ] ( suvmax= 5.3 ; liver suvmax= 2.3 s / l ratio = 2.30 ) .\nthe first differential in the given clinical scenario was splenic relapse of lymphoma , however , a second differential diagnosis of some infective / inflammatory process was considered .\non further evaluation , peripheral smear showed evidence of malaria parasite infection ( plasmodium vivax ) .\nfollow - up pet / ct after 7 months revealed normalization of size and f - fdg uptake of spleen [ figure 2d , arrow ] ( suvmax= 3.0 ; liver suvmax= 2.7 s / l ratio = 1.1 ) .\nhence , malaria and other relevant ( endemic ) infective possibilities ( kala - azar etc . ) should be considered and further investigation , if warranted , should be advised .\nf - flurodeoxyglucose ( f - fdg ) positron emission tomography/ computed tomography ( pet / ct ) done for staging and response evaluation .\n( a ) staging maximum intensity projection ( mip ) pet image showing multiple metabolically active lymph nodes in thorax , abdomen and pelvis ( broken arrows ) with splenic ( arrow ) and bone lesion ( left femur ) .\n( b ) mip pet image done for response evaluation demonstrates complete metabolic response with normal splenic fdg uptake ( arrow ) .\nphysiological gastric fdg uptake noted ( bent arrow ) f - flurodeoxyglucose ( f - fdg ) positron emission tomography / computed tomography ( pet / ct ) done for recurrence detection and follow - up .\n( a - c ) follow - up pet / ct performed 1 year after chemotherapy showing enlarged spleen with diffusely increased fdg uptake ( arrow ) .\n( d ) maximum intensity projection pet image performed after anti - malarial therapy , showing normalization of size and fdg uptake of spleen ( arrow ) . ( a and d )\nfocal fdg uptake noted in the pelvis is due to urinary fdg activity in the left ureter ( curved arrows )\npet / ct is a useful modality for staging and restaging of hodgkin 's lymphoma with high sensitivity and specificity .\nfurthermore , it is a sensitive modality for early detection of relapse in asymptomatic patients making surveillance f - fdg pet / ct clinically important .\nsplenic uptake on f - fdg pet can be due to a wide variety of causes such as lymphoma , anemia , granulocyte colony stimulating factor treatment , beta - thalassemia , inflammation and infections .\nsplenic uptake , greater than hepatic uptake , is a relatively reliable indicator of lymphomatous involvement of the spleen , in the absence of recent cytokine administration . in early stage hiv infection , diffusely increased splenic uptake is noted due to reactive stimulation of b - cells in the spleen .\npost - therapeutic reactive splenic uptake is also noted after administration of granulocyte colony - stimulating factor for myelosuppression or high - dose interferon - alpha-2b adjuvant therapy for melanoma . until date , only a single report by liu et al . have demonstrated f - fdg uptake in spleen in case of malaria .", "answer": "18flurodeoxyglucose ( 18f - fdg ) positron emission tomography / computed tomography ( pet / ct ) is nowadays routinely used in management of lymphoma patients . \n we here present a case of hodgkin 's lymphoma which showed 18f - fdg avid splenomegaly on pet / ct done for clinically suspected relapse . \n further evaluation by peripheral smear examination revealed malaria . \n the patient was then started on anti - malarial medications and follow - up pet / ct revealed resolution of hypermetabolic splenomegaly . \n this report highlights that in endemic regions malaria can cause 18f - fdg avid splenomegaly and might mimic relapse of lymphoma .", "id": 244} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsubependymoma , first described by scheinker in 1945 , is a rare central nervous system tumor . since its first description in the spinal cord by boykin et al in 1954 ,\n32 involved the cervical cord . in the spinal region , these lesions are predominantly subpial in location , with exophytic components .\nthe location of these lesions in the spinal cord suggest a subpial glial progenitor origin rather than its proposed origin from subependymal progenitor cells.[14 ]\na 37-year - old lady presented to us with complaints of neck pain and gait disturbances of 1 year duration with severe progressive weakness of her right upper limb since 3 months .\nmri revealed a long - segment t2 hyperintense intramedullary lesion opposite to the c3 to d4 vertebral levels with mild heterogeneous enhancement on the post contrast study [ figure 1 ] .\n( a ) sagittal t2 and ( b ) post contrast t1-weighted mr images showing a long segment t2 hyperintense and mild hetrogenous enhancing lesions in the cervical cord , showing cord expansion .\nintraoperatively , the lesion was firm , with a poor plane of demarcation from the normal cord , and was seen intermingling with posterior and anterior nerve rootlets .\nit was eccentric in location , involving more of the left hemicord , with exophytic components [ figure 2 ] .\nsurgical finding : typical exophytic subpial lesions , with lesion on either sides of the dorsal nerve roots .\nall of the resected tissue submitted for histopathological analysis was processed and embedded in three paraffin blocks .\nhistopathological examination [ figure 3 ] revealed characteristic features of a subependymoma ( who grade 1 ) with small monomorphic cells arranged in a lobular pattern against a finely fibrillary background , with occasional rosette like pattern .\nfeatures of pleomorphism , mitotic activity , endothelial cell proliferation , and necrosis were not seen .\nthe mib-1 proliferative index was low ( < 1% of tumor cells ) ( ) . immunohistochemistry revealed diffuse positivity for glial fibrillary acidic protein ( gfap ) , whereas tumor cells failed to express epithelial membrane antigen ( ema ) .\nhistopathology : ( a ) h and e staining shows lobular pattern arrangement of monomorphic nuclei in fibrillary pattern ( 400 ) .\n( b ) mib-1 labeling index is less than 1% of tumor cells ( not shown in figure ) ( 400 ) .\nimmunohistochemistry for ( c ) gfap highlights diffusely positive tumor cells in a fibrillary background ( 400 ) ( d ) tumor cells are negative for ema ( 400 ) she did not receive any adjuvant treatment and has been on follow up for 6 months with periodic mr imaging .\nsubependymomas are rare central nervous system tumors accounting for 0.7% of all intracranial neoplasms and 8.3% of all ependymal tumors .\nthey are located most frequently in the fourth ventricle ( 5060% of cases ) followed by the lateral ventricles ( 3040% ) .\nso far , only 47 cases have been reported in the english literature in the spinal cord ; of which 32 cases were located in the cervical , cervico - medullary , and cervico - thoracic locations .\nmost are intramedullary in location , with few subarachnoid and extramedullary variants mentioned in the literature .\nthe symptomatic subependymoma generally occur after 40 years of age and are rare in childhood.[13 ] the salient features 33 in cases of cervical subependymomas they have a mean age of presentation of about 44 years with a strong male preponderance [ table 2 ] .\nepidemiology of spinal subependymomas ( including our case).[16 , 814 ] histopathologically these tumors are low grade ( who grade 1 ) , characterized by homogenous cells with sparse cellularity showing clustering of nuclei over a fibrillary background formed by cell processes and occasional occurrence of microcysts .\nthe tendency to form pseudorosettes and the cells being round with hyperchromatic nuclei are reminiscent of ependymomas .\nimmunohistochemical characteristics are however identical to that of astrocytic neoplasms with diffuse gfap and s-100 protein positivity . in contrast to ependymomas ,\nthe former is evidenced by the processes containing intermediate filaments and the latter by microlumens , cilia , microvilli , and intercellular junctions .\nthe histogenesis of these tumors has been much debated . due to their ultrastructural similarities with ependymal cells\n, they were initially thought to arise from ependymal cells , with reactive astrocytic proliferation .\nsince immunohistochemical profile favors a glial origin , they were grouped with low - grade glial tumors .\ntanycytes were also proposed as source of origin , due to the presence of ultrastructural features of glial as well as ependymal components .\nhowever , the presence of round cells rather than spindle - shaped cells differentiates these lesions from tanycytic ependymomas .\nthe identification of cells similar to subependymal glial precursor cells suggested alternate cell of origin .\nsubependymal zone glial precursor cell origin can not explain the predominant peripheral and exophytic location of these lesions in spinal cord unlike their intracranial counterparts .\nthe current concept seems to suggest that these progenitor cells exist throughout the spinal cord white matter as well as the root entry zones .\nthey are more localized in the outer subpial white matter than the medial zones , especially at the dorsal and ventral spinocerebellar tracts .\nthey tend to proliferate within their template zones and do not possess trans - zonal migratory ability .\nthe tumor origin from these cells better explains the eccentric , subpial , and exophytic locations of spinal subependymomas .\nthe progenitor cells origin postulated by horner et al is an alternative to the conventional old postnatal theory [ type 1 , figure 4 ] where the progenitor cells migrate from the subependymal zone to the outer zones .\nthere are two alternative postulates : one where the stem cell divides asymmetrically and the daughter cell migrates to the outer white matter where it remains as a glial progenitor cell and multiplies [ type 2 , figure 4 ] , and the second which postulates that the stem cells exist separately in the outer zone where tracts are constantly proliferating even postnatally and these give rise progenitor glial cells [ type 3 , figure 4 ] .\n( a ) post natal theory : where the subependymal stem cells give rise to glial progenitor cells which then migrate to the periphery .\n( b and c ) alternate new theories where the stem cells themselves migrate to the periphery and become glial progenitor cells ( b ) or the stem cells already existing in the periphery of the cord become glial progenitor cells ( c ) .\nirrespective of their origin the subpial spinal white matter progenitor cells may be the origin of the spinal subependymoma .\nthe subependymomas reported are more commonly located in the cervical cord and the cervico - thoracic cord followed by the pure thoracic and lumbar segments .\none rare case occurring in the filum teminale has also been reported [ table 2 ] .\nradiologically , these lesions are located eccentrically within the cord , with iso or hypointense on t1-weighted images and mild hyperintensity on t2-weighted images .\nthere is minimal diffuse or no enhancement on contrast.[148 ] these lesions can usually be excised totally .\nonly three cases have been reported with recurrence of the tumor after initial total excision .\nall of them had a resurgery and were not subjected to adjuvant radiation or chemotherapy despite recurrence .\nthe chances of recurrence after total excision are low ; hence , a total excision should always be attempted [ tables 1 and 2 ] . however , as with our case , the size of the lesion and its extensive intermingling with the nerve roots made it sometimes necessary to settle for a subtotal excision .\nthere have been instances of postoperative radiation following subtotal excision , but it is generally not recommended .\nresidual or recurrent tumor on follow up after gross total resection should be strongly considered for a re - excision rather than adjuvant therapy.[268 ]", "answer": "subependymomas are extremely rare lesions of the spinal cord . \n only 33 cases including ours have been reported in the cervical cord . \n these are typically benign slow growing tumors occurring eccentrically within the cord , producing minimal neurological deficits . \n the clinical , radiological , and histopathological aspects of this unusual lesion have been reviewed in detail . \n as the histogenesis of this tumor is much debated , we propose an alternate origin for the same .", "id": 245} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmetastasis of transitional cell carcinoma ( tcc ) of the renal pelvis to the eye is a very rare event and has only been reported in one case in the literature .\nonce diagnosed , these cases usually show widespread metastases and carry a very poor prognosis .\nwe present a case report of a male patient with unilateral choroidal metastasis secondary to tcc of the renal pelvis .\nreview of the relevant literature will be addressed to highlight the involvement of the choroid in cases of metastatic disease , the unusual presentation of tcc , diagnostic methods , and the various therapeutic modalities used to treat these cases .\na 61-year - old male , who has a history of congestive heart failure , is a nonsmoker , and has no significant family history of malignancies , presented to the ophthalmology clinic with sudden - onset loss of vision of the left eye associated with intermittent left eye pain , relieved by analgesics\n. ophthalmic evaluation revealed a visual acuity of 20/40 in the right eye and 20/400 in the left eye .\nfunduscopic examination of the left eye showed an amelanotic macular choroidal lesion associated with inferior exudative retinal detachment ( fig 1a ) .\na b - scan ocular ultrasound showed a dome - shaped , 2.8-mm choroid thickening with variable internal reflectivity , associated with inferior exudative retinal detachment ( fig 1b ) .\nfluorescein fundus angiography revealed early choroid blockage ( fig 1c ) and late leakage associated with hot spots at tumor margin .\nall of these clinical features are suggestive of the clinical diagnosis of left choroidal metastasis .\nphysical examination of the patient also revealed multiple suspicious chest wall nodules . in search for a primary malignancy ,\nimaging studies were done , which revealed multiple pulmonary and liver metastasis , subcutaneous metastasis , multiple lymphadenopathies , and left renal upper pole mass ( fig 2 ) .\nct - guided left renal mass biopsy and ultrasound - guided biopsy of the left chest wall subcutaneous mass were performed .\nthey are negative for ck20 , pax2 , ttf-1 , synaphopysin , and s100 ( fig 3 ) .\nexternal beam radiation therapy ( ebrt ) is a common mode of treatment and will be considered if there is no improvement of visual symptoms with chemotherapy .\nchoroidal metastasis is the most common intraocular malignancy , due to its rich vascular supply and high oxygen concentration [ 4 , 5 ] .\nless common primary cancers include the thyroid , prostate , kidney , testicles , pancreas , ovary , and liver .\nrarely is it seen in cases of tcc , as there have only been 5 previous reports in the literature involving choroidal metastasis , 3 from tumors involving the bladder , and 2 from other parts of the urinary tract .\nchoroidal metastasis is commonly associated with disseminated disease and , unfortunately , carries a very poor prognosis .\ntcc usually metastasizes to the regional lymph nodes ( 78% ) , liver ( 38% ) , lung ( 36% ) , bone ( 27% ) , adrenal gland ( 21% ) , and intestine ( 13% ) .\nthe heart , brain , kidney , spleen , pancreas , meninges , uterus , ovaries , prostate , and testes have been reported as unusual sites of presentation of tcc .\nother less common clinical presentations include flashes ( 5% ) and floaters ( 5% ) .\ndiagnosis is based on clinical findings , which are typically seen as yellow , plateau - shaped lesions associated with subretinal detachment .\na - scan and b - scan ultrasonography show irregular internal reflectivity and a solid plateau - shaped mass , respectively .\nfluorescein fundus angiography typically shows mottled hypofluorescence in early stage and leakage in late stage .\nthe treatment of choroidal metastasis should be individually tailored , taking into consideration the patient 's systemic state , disease activity , and the presence of visual symptoms .\nits aim is palliation , to improve the quality of life of the patient and to restore or maintain visual function .\nlocal therapeutic regimens include ebrt , plaque radiotherapy , and complete enucleation for painful , blind eyes [ 13 , 14 ] .\nebrt delivered at a dose of 40 gy over 20 fractions was effective in improving and maintaining vision in patients with choroidal metastasis [ 15 , 16 ] . in cases of widespread metastases , systemic chemotherapy alone or in combination with local therapy is an accepted therapeutic option . in patients with choroidal metastasis alone ,\nlocal therapy has been reported to be safe , maintaining visual functions without the systemic side effects of chemotherapy .\nchoroidal metastasis related to tcc of the renal pelvis is an extremely rare event and is associated with widespread disease and a very poor prognosis\n. systemic chemotherapy with carboplatin and gemcitabine is a palliative treatment option for this patient .\nebrt offers local palliation and will be considered according to the patient 's visual response to chemotherapy .", "answer": "metastases of transitional cell carcinoma ( tcc ) of the renal pelvis to the eye is a very rare event , as only one previous case has been described in the literature . \n we present a patient with choroidal metastasis secondary to tcc of the renal pelvis , with a review of the relevant literature . a 61-year - old male presented with sudden - onset loss of vision of the left eye . upon evaluation and assessment , \n the patient was found to have unilateral choroidal metastasis secondary to tcc of the renal pelvis . \n he is currently on palliative chemotherapy with carboplatin and gemcitabine . \n external beam radiation therapy is a common mode of treatment and will be considered accordingly .", "id": 246} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe number of patients undergoing chemotherapy grows year by year . despite their efficacy in controlling the cancer , chemotherapy drugs are not inert , and they cause damage to the human body\nregarding nail involvement , diverse clinical features can be observed , according to the structure affected and the severity of the damage caused .\nthe most common chemotherapeutic agents implicated in nail changes are cyclophosphamide , doxorubicin and hydroxyurea [ 2 , 3 ] . in the majority of cases ,\nthe effects are fully reversible after a few months once the causative agent has been withdrawn [ 2 , 4 ] .\na 25-year - old male patient was admitted to the hospital 's hematology ward with the diagnosis of acute lymphocytic leukemia .\nthe hyper - cvad regimen delivers a combination of drugs in 2 cycles ( cyclophosphamide , vincristine , doxorubicin and dexamethasone in cycle a , methotrexate and cytarabine in cycle b ) , split into smaller doses and administered at more frequent intervals in order to minimize side effects . during hospitalization , a dermatology assessment was requested .\nthe dermatological examination showed nail injury characterized by transverse , brown - gray hyperpigmentation affecting the proximal half of the nail plate , with a brown band delimiting the healthy nail plate on all fingers ( fig . 1 , fig\nchromonychia induced by chemotherapeutic agents has different forms , the most common being melanonychia [ 2 , 4 , 5 ] . the dark pigmentation in nails can be diffuse , transverse or longitudinal and can coexist with skin and mucosal pigmentation [ 2 , 4 , 6 ] .\nit has been suggested that chemotherapy drug regimens influence the incidence of changes that may result from toxicity in the nail matrix , nail bed , periungual tissue and digits vessels [ 2 , 6 ] .\nalthough several chemotherapeutic agents can cause these changes , those most associated with these side effects are cyclophosphamide , doxorubicin and hydroxyurea [ 2 , 3 ] .\ncyclophosphamide is an alkylating agent whose main target is the cell cycle ; thus , tissues with high proliferation rates are more susceptible .\nalkylating agents form cross - links with dna filaments and prevent dna replication , therefore entailing cytotoxicity .\ncyclophosphamide can cause nail changes such as diffuse , black pigmentation , longitudinal striae ranging in color from slate gray to black , and diffuse , dark gray pigmentation located proximally , with overlying transverse , black bands [ 2 , 4 ] .\nthis drug - induced nail pigmentation starts from the proximal edge of the nail and proceeds towards the distal edge . upon withdrawal of the drug\nit takes approximately 46 months [ 2 , 3 ] . in 60% of patients ,\ncyclophosphamide is also associated with pigmentation of the oral mucosa and tongue , which also regresses upon withdrawal of the drug [ 2 , 4 ] .\nits side effects include skin and nail hyperpigmentation , alopecia , skin rash , pruritus , photosensitivity , urticaria , acral erythema and palmoplantar erythrodysesthesia .\nnail changes such as transverse , dark brown bands alternating with white stripes [ 2 , 7 ] and dark brown diffuse pigmentation bands 45 mm wide , which affect two - thirds of the distal portion of the nail , also occur [ 2 , 5 ] .\nadditionally , doxorubicin can cause subungual keratosis , onycholysis and thickening of the nail plate .\nhydroxyurea causes an immediate inhibition of dna synthesis by acting as an inhibitor of ribonucleotide reductase , without interfering in the synthesis of ribonucleic acid or protein .\nthis pigmentation has a diffuse , dark brown color which may appear as single or double transverse bands [ 2 , 4 ] .\nungual hyperpigmentation induced by chemotherapy is not uncommon , although its occurrence is underestimated and seldom reported , especially in patients with dark skin phototypes , such as our patient , in this case , the drugs most probably implicated are doxorubicin and cyclophosphamide because they produce ungual alterations very similar to the ones seen in our patient ; his chemotherapeutic scheme included both of them .", "answer": "chemotherapy drugs can affect the skin and its appendages . \n several clinical presentations can be observed , depending on the affected structure . \n the most common dermatological side effect is chromonychia . \n the main causative agents are : ( 1 ) cyclophosphamide , which can provoke a diffuse , black pigmentation , longitudinal striae and dark grey pigmentation located proximally on the nails ; ( 2 ) doxorubicin , which promotes dark brown bands alternating with white striae and dark brown pigmentation in transverse bands , and ( 3 ) hydroxyurea , which produces a distal , diffuse , dark brown pigmentation . in the majority of cases , \n the effects are reversible after the suspension of the causative agent for a few months . \n we report a patient who developed chromonychia while undergoing treatment with cyclophosphamide , vincristine , doxorubicin , dexamethasone , methotrexate and cytarabine for acute lymphocytic leukemia .", "id": 247} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey may be the first manifestation of metastatic spread of an internal malignancy or herald cancer recurrence long after treatment of a primary tumor .\nbreast cancer , colorectal cancer , and melanoma frequently metastasize to the skin in women . in men ; melanoma , lung cancer , and colorectal cancer are the most common sources of cutaneous metastases .\nhowever , such patterns may differ geographically as a study in taiwan found internal malignancies metastasize to the skin with different frequencies and at rates differing from primarily caucasian populations .\nan extensive literature review was conducted using pubmed from may 26 , 2011-july 16 , 2013 relating cutaneous metastases .\narticles chosen for reference were queried with the following prompts : cutaneous metastases , clinical presentation , histological features , and\nfurther searches included treatment and management options for metastatic breast , metastatic colorectal , metastatic melanoma , metastatic lung , and hematologic cancers .\nwe review the literature on clinical presentation , diagnosis , and advances in the management .\ncutaneous metastases may be asymptomatic or be associated with pain and tenderness [ figure 1a ] .\nthey frequently present as a rapidly growing painless dermal or subcutaneous nodules with intact overlying epidermis [ figures 1b d ] , but can also mimic an inflammatory dermatosis .\nmetastases may also present as macules , infiltrated or indurated plaques , discoid lesions , tumor nodules with telangiectasias , bullous or papulosquamous lesions , scarred plaques , or pigmented tumors . while there is no single diagnostic characteristic which predominates ; a few patterns have been recognized .\n( a ) gingival metastases from a primary chondrosarcoma.(b ) firm nodule at the base of the ear from a primary lung cancer .\n( c ) two subcutaneous firm nodules in the clavicular fossa from metastatic lung cancer .\n( d ) isolated firm nodular lesion from metastatic colon cancer metastases originating from breast cancer tend to appear in the anterior chest wall , either from direct extension of underlying tumor or by lymphatic spread [ figures 2a and 3a ] .\nextensive cutaneous involvement of metastatic breast cancer can simulate cellulitis ( carcinoma erysipeloides ) or a breast - plate of armor ( \" en cuirasse \" pattern ) .\ninterestingly , a subset of breast cancer patients has superior prognosis , even among breast cancer patients with stage iv disease .\n( a ) cellulitis - like appearance of metastatic breast cancer.(b ) plaque - like area with multiple nodules from a primary breast cancer .\n( c ) massive recurrence of breast cancer on the chest wall and abdomen of the en cuirasse type .\n( d ) breast cancer , metastatic to the thoracic spine with extension to the skin , and lceration secondary to radiation therapy ( a ) cellulitic - type appearance with multiple nodules in metastatic breast cancer of the shoulder and upper back .\na cam 5.2 stain reveals perinuclear staining ( original magnification , 400).(c ) metastatic squamous cell carcinoma of the skin reveals neoplastic cells in the dermis ( cytokeratin 5/6 stain ; original magnification , 100 ) .\na her2/neu stain is positive and decorates the neoplastic cells in the dermis indicating possible metastasis from breast carcinoma ( original magnification , 200 ) while most cancers present as solitary nodules , melanoma and carcinomas with an unknown primary frequently present as multiple nodules .\nlocoregional melanocytic metastases may be explained by angiotropism , an extravascular migratory phenotype , and an important marker and prognostic factor of metastasis in melanoma .\nthe face and scalp are most commonly affected by metastases , suggesting that blood vessels and patterns of innervation may influence the spread of metastases .\nthese patterns can also been associated with cancers of gastric , pulmonary , prostatic , ovarian , laryngeal , palatine - tonsillar , pancreatic , colorectal , parotid , thyroid , or uterine origin and may suggest local treatments that work for melanoma may also work for other metastatic cutaneous malignancies .\nalthough metastases may be comprised of cells which are more undifferentiated than the primary tumor , careful examination usually reveals important clues .\nfor example , melanoma is associated with pigment in at least some of the neoplastic cells in most cases .\nsquamous cell carcinoma is associated with keratin pearl formation , and adenocarcinomas usually exhibit gland formation .\nthyroid cancer may exhibit colloid bodies , colon cancer may be associated with mucinous cells , and other tumors may exhibit telltale clues as to their origin . when confronted with a possible metastasis ,\ncomparison with the histologic appearance of any prior malignant neoplasms is usually one of the first steps that may help identify the source .\nadditionally , studies have indicated the majority of metastatic cancers to the skin are adenocarcinomas .\nwhen tumors are poorly differentiated or anaplastic , screening immunohistochemical studies can be very helpful .\nwhen neoplastic cells stain with cytokeratin markers such as ae1/ae3 and cam 5.2 , a carcinoma is likely [ figure 3b ] .\nstaining with cd45/leukocyte common antigen ( lca ) indicates that neoplastic cells are of lymphoid origin , while s-100 , melan - a , mart-1 , hmb-45 , and sox-10 decorate most melanomas .\nmore detailed immunohistochemical studies [ table 2 ] can be performed when screening studies and clinical correlation have not been fruitful in identifying a tumor of origin .\nalthough advances in immunohistochemistry are very promising , there is still much work that needs to be done to characterize metastases .\na recent letter to the editor highlights the pitfalls that can occur when differentiating primary cutaneous apocrine carcinoma from a metastasis .\nalthough cytokeratin 5/6 is associated with cutaneous apocrine carcinoma , this staining pattern has also been noted with metastatic squamous cell carcinoma [ figure 3c ] .\nsimilarly , cytokeratin 7 usually stains metastases diffusely , but is associated with only focal staining in primary adnexal carcinoma , but this pattern is not absolute .\nmammaglobin is of interest as it is associated with more widespread staining of metastases than primary apocrine carcinoma , but the results are still preliminary .\ncyclooxygenase 2 is associated with tumors of the mid - gut ( ileum and appendix ) , gut , colorectal adenocarcinoma as well as gastroesophageal adenocarcinoma .\nstaining of adenocarcinoma of the lung and endometrioid adenocarcinoma can also occur , highlighting the fact that all immunochemical marker studies must be interpreted in the context of other findings .\nwhen an epithelial carcinoma is identified , cytokeratin 7 and 20 stains can provide important useful characterization of tumors .\nadditional testing can include thyroid transcription factor-1 ( ttf-1 ) and other markers as needed . when clinical appearance , clinical history , and the histologic findings on biopsy are all taken into account\nunfortunately , there are still many cases that elude precise diagnosis regarding whether a tumor is primary or metastatic .\nrecent reports have proposed a diagnostic algorithm for metastatic tumors of unknown primary . until better methods are developed\nwe recommend excising metastases when surgically feasible and when this will result in a significant decrease in total tumor burden , improve quality of life , or result in increased functionality .\nnovel treatments have had a profound effect on prolonging the survival and improving quality of life with metastatic cancer .\noftentimes , treatment of the primary cancer with a successful regimen will cause cutaneous lesions to lessen .\ninterestingly , the abscopal response represents an unusual response to radiation therapy in which radiation of a tumor causes untreated distant skin lesions to dissipate without recurrence .\nthe pathophysiology and mechanism of the abscopal effect have not been well - defined , but one study used monoclonal antibodies to analyze infiltrating lymphocytes and suggested that the abscopal effect was caused by activated cellular immunity .\nthe abscopal response has been reported with treatment of melanoma , merkel cell carcinoma , hematologic , and solid tumors .\nthe study of effective local treatments for melanoma may serve as a model for other malignancies that disseminate via lymphatics and the blood stream to the skin . for melanomas ,\nwe typically excise isolated metastases with a 1 cm margin of normal skin , understanding that there are no evidence based studies looking at the utility of margins for metastatic disease . in areas of high cosmetic importance or when therapy is limited to palliation\n, we sometimes perform excisions with very limited margins . therapy for patients with widespread cutaneous and subcutaneous metastases of advanced melanoma that are nonresectable is limited to other types of palliative therapy .\noptions include radiotherapy , systemic chemotherapy , polychemotherapy , isolated limb perfusion , interferon alpha injections , cryotherapy , laser ablation , or radiofrequency ablation .\nelectrochemotherapy is a novel therapeutic option based on enhanced drug delivery into cancer cells using externally applied electrical fields that increase cell membrane permeability . using targeted electric pulses on tumor - specific areas , cytotoxicity of cisplatin\nincreased 80 times and bleomycin 8,000 times with a large reduction in systemic side effects .\na study comparing tumor nodules treated with electrochemotherapy with cisplatin versus cisplatin alone found at a 124-week follow - up , 77% of control rate of tumor nodules treated with electrochemotherapy was observed compared to 19% for those treated with cisplatin only .\nelectrochemotherapy is well - tolerated by patients , highly effective with low doses of cisplatin or bleomycin , has a short duration of treatment sessions , insignificant side effects , and is more cost - effective than isolated limb perfusion , radiotherapy , interferon - alpha , and hyperthermia associated with radiotherapy and chemotherapy .\noncogene - targeted therapy for metastatic melanoma using vemurafenib ( plx4032 ) for melanoma associated with a mutation of the braf gene v600 mutation results in complete or partial tumor regression in the majority of patients with an estimated median progression - free survival of more than 7 months .\nside effects include arthralgia , rash , nausea , photosensitivity , fatigue , cutaneous squamous - cell carcinoma , pruritus , and palmoplantar dysesthesia .\nimiquimod 5% cream has also been used successfully in the treatment of metastatic melanoma that is difficult to remove by surgery . in one report ,\na 58-year - old woman with a superficial spreading melanoma with a breslow thickness 0.75 mm was treated with wide local excision followed by flap reconstruction .\nmelanoma reemerged 14 months later that was treated with wide local excision followed by split - thickness graft repair .\nthe patient was enrolled in a melanoma peptide vaccine trial 5 months later without improvement .\ntwenty - one months later , the patient was treated with imiquimod 5% cream and histopathologic evaluation revealed regression of the widespread cutaneous metastases after 6 months of imiquimod .\nany change in the skin should raise the suspicion of metastases in the correct clinical context .\nbiopsy is mandatory in patients with a history of cancer or those with at high risk of cancer .\nimmunohistochemical screening methods continue to improve and assist in diagnosing the primary tumors of origin .\nimmunohistochemical findings can also help direct treatment options . with advances in novel therapies that prolong survival ,", "answer": "skin metastases are rare in the routine clinical practice of dermatology , but are of major clinical significance because they usually indicate advanced disease . \n we reviewed the literature on skin metastasis regarding recent trends in clinical presentation and diagnosis of the most common cutaneous lesions . \n an extensive literature review was conducted using pubmed from may 26 , 2011 to july 16 , 2013 relating cutaneous metastases . \n articles chosen for reference were queried with the following prompts : cutaneous metastases , clinical presentation , histological features , and \n immunohistochemistry . \n further searches included treatment and management options for metastatic breast , metastatic colorectal , metastatic melanoma , metastatic lung , and hematologic cancers . \n we also reviewed the literature on the current management of melanoma as a model for all cutaneous metastatic disease . \n our own clinical findings are presented and compared to the literature . \n additionally , we highlight the most useful immunohistochemical studies that aid in diagnoses . \n several novel therapies and combination therapies such as electrochemotherapy , vemurafenib , and imiquimod will be discussed for palliative treatment of cancers that have been found to improve cutaneous lesions . \n we review these notable findings and developments regarding skin metastases for the general dermatologist .", "id": 248} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbenign prostatic hyperplasia ( bph ) is a progressive and androgen - dependent disease that causes lower urinary tract symptoms ( luts ) .\nalthough bph is not a life - threatening disease , it can have a negative effect on the quality of life .\nalpha - adrenergic receptor antagonists ( -blockers ) and 5-alpha reductase inhibitor ( 5ari ) are the first - line treatment option in patients with bph .\n5ari blocks the conversion of the sex steroid hormone testosterone to dihydrotestosterone ( dht ) , which is an essential component of bph pathogenesis .\nprevious studies reported that the serum prostate - specific antigen ( psa ) level and prostate volume were decreased by approximately 50% and 20% , respectively , after treatment with 5ari .\nhowever , some clinical questions remain as to how to interpret the psa level in men treated with 5ari .\nfurthermore , the effects on luts and prostate volume after discontinuation of 5ari are not well understood .\ntherefore , in the present study , we analyzed the changes in luts , prostate volume , and psa level after discontinuation of 5ari .\nfrom december 2003 to december 2012 , 81 men more than 40 years of age with moderate to severe bph symptoms as determined by the international prostate symptom score ( ipss8 ) and a prostate volume of greater than 25 cm measured by transrectal ultrasonography ( trus ) were collected retrospectively for the study .\ntwo patients ( case 1 , 4.91 ng / ml ; case 2 , 5.43 ng / ml ) with a psa level of 4 or more and with a negative pathologic result on the initial prostate biopsy were included in the study .\npatients were excluded from the study if they had chronic urinary tract infection ; a history of prostate or testicular surgery , prostate cancer , acute urinary retention , or chronically large postvoid residual urine volume ; or 5ari treatment history .\nthe patients were classified into group 1 ( n=42 ) and group 2 ( n=39 ) according to 5ari use .\na combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year .\n, group 1 ( n=42 ) received a combination of dutasteride 0.5 mg with tamsulosin 0.2 mg daily , and group 2 ( n=39 ) received -blocker monotherapy only .\nthe ipss , prostate volume , and psa level were measured at baseline and at 12 and 24 months . with trus ( aloka , tokyo , japan ) , prostate volume was measured by use of the prostate ellipsoid formula and was calculated by multiplying the longest anteroposterior ( height , h ) , transverse ( width , w ) , and cephalocaudal ( length , l ) diameters and 0.524 ( hwl/6 ) .\npasw ver . 18.0 ( ibm co. , armonk , ny , usa ) was used for all statistical analyses .\nstudent t - test was used to compare the baseline values of ipss , prostate volume , and serum psa level in each group .\nthe repeated - measures analysis of variance was performed to compare the change in ipss , prostate volume , and psa level from 0 to 12 months and also from 12 months to 24 months .\nthe mean age of the patients ( n=81 ) was 71.70 years ( standard deviation [ sd ] , 7.80 ) .\nthe mean prostate volume was 43.96 cm ( sd , 17.38 ) and the mean baseline serum psa level was 3.00 ng / ml ( sd , 1.98 ) .\nthe patients were classified into group 1 ( n=42 ) and group 2 ( n=39 ) .\nthere were no statistically significant differences between the two groups in mean age , total ipss , baseline prostate volume , or psa level ( table 1 ) .\nthe differences in total ipss , prostate volume , and serum psa level according to the absence of dutasteride are shown in table 2 . at 1 year after combination therapy , total ipss\nhad decreased by 17.6% ( from 17.88 [ sd , 7.77 ] to 14.95 [ sd , 7.27 ] ; p<0.001 ) in group 1 and by 13.3% ( from 15.50 [ sd , 7.60 ] to 13.45 [ sd , 2.50 ] ; p<0.001 ) in group 2 . however , at 1 year after dutasteride had been withdrawn , total ipss had increased by up to 7.6% ( from 13.45 [ sd , 2.50 ] to 14.93 [ sd , 5.48 ] ; p<0.001 ) in group 2 ( table 2 ) . at 1 year after combination therapy , the prostate volume was reduced by 21.9% ( from 41.59 cm [ sd , 13.97 ] to 32.95 cm [ sd , 10.10 ] ; p<0.001 ) in group 1 and by 15.5% ( from 45.96 cm [ sd , 23.02 ] to 38.96 cm [ sd , 23.91 ] ; p<0.001 ] in group 2 . at 1 year after dutasteride had been withdrawn , the prostate volume had increased by up to 13.1% [ from 38.96 ( 23.91 ) cm to 43.82 ( 23.45 ) cm ; p<0.001 ] . at 1 year after combination therapy ,\nthe transition zone volume had been reduced by 20.0% ( from 15.62 cm [ sd , 5.76 ] to 12.23 cm [ sd , 4.50 ] ; p<0.001 ] in group 1 and by 17.6% ( from 17.84 cm [ sd , 10.35 ] to 14.61 cm [ sd , 9.81 ] ; p<0.001 ] in group 2 . at 1 year\nafter dutasteride had been withdrawn , the prostate volume had increased by up to 14.2% ( from 14.61 cm [ sd , 9.81 ] to 16.46 cm [ sd , 10.06 ] ; p<0.001 ] in group 2 .\nthe psa level had decreased by 48.4% ( from 3.30 ng / ml [ sd , 2.09 ] to 1.75 ng / ml [ sd , 1.33 ] ; p<0.001 ) in group 1 and by 49.4% ( from 2.67 ng / ml [ sd , 1.82 ] to 1.35 ng / ml [ sd , 0.92 ] ; p<0.001 ) in group 2 .\nhowever , 1 year after discontinuation of dutasteride , the psa level had increased up to 108.2% of the baseline level ( from 1.35 ng / ml [ sd , 0.92 ] to 2.89 ng / ml [ sd , 2.10 ] ; p<0.001 ) in group 2 ( fig .\nthe changes in ipss , prostate volume , and psa over time also did not differ significantly between groups 1 and 2 ( table 2 ) .\npatients discontinued dutasteride in group 2 owing to adverse events , including loss of libido ( n=9 ) or erectile dysfunction ( n=17 ) , lack of therapy efficacy ( n=7 ) , abnormal ejaculation ( n=5 ) , and gynecomastia ( n=1 ) .\nthese symptoms may be associated with bph , which causes extrinsic compression of the prostatic urethra leading to impaired voiding .\nbph is a common disease in aging men that leads to deterioration in symptoms , acute urinary retention , bph - related prostatic surgery , gross hematuria , urinary tract infection , bladder stones , and renal insufficiency .\nmen who have a prostate volume of more than 30 ml are more likely to have moderate - to - severe symptoms ( 3.5 times ) , decreased flow rates ( 2.5 times ) , and acute urinary retention ( 3 - 4 times ) than are men with a prostate volume of less than 30 ml .\nbph can significantly affect quality of life in a negative direction , thus requiring treatment .\nbph can be managed medically with alpha - blockers , 5-ari , or a combination of both .\nalpha - blockers relax the smooth - muscle tone in the prostate and bladder neck .\nhowever , alpha - blockers do not provide long - term reduction in the risk of acute urinary retention or bph - related surgery .\nthe main role of 5ari is to induce glandular epithelial atrophy , which causes volume reduction in the prostate .\n5ari is responsible for impeding the conversion of testosterone to dht by inhibiting the nuclear - bound steroid 5-reductase ( 5ar ) isoenzymes .\nboth normal prostate development and hyperplasia of the prostatic transitional zone are regulated by dht .\nmen taking 5ari have a 57% reduction in the risk of acute urinary retention compared with those taking placebo and a 34% reduction in the risk of surgery .\ndutasteride results in a reduction of 20% or more in the size of the prostate and a reduction of 48% in the risk of bph - related surgery . in our study ,\ntotal ipss improvement and prostate volume reduction were evident in all men after treatment with dutasteride 0.5 mg .\nfew reports have discussed the effect of discontinuation of 5ari on luts , prostate volume , and psa level .\nstoner demonstrated that the prostate volume returned to near the baseline values at 12 weeks after discontinuation of 5ari . in our study , the mean percentage of prostate regrowth had reached 95.5% of the baseline prostate volume 1 year after discontinuation of dutasteride . owing to the complex etiologies of prostate enlargement , the mechanism of prostate regrowth after 5ari withdrawal is not fully understood .\nthe hyperplastic changes in bph are an androgen - dependent process , and it is possible that the sensitivity to dht is increased or overly activated as a result of the prolonged pharmacologic inhibition of 5-reductase by the 5ari .\nandrogen receptors , which become more sensitive or up - regulated during treatment with 5ari , may be considered as an alternative mechanism .\nour study showed that the total ipss had increased 1 year after cessation of dutasteride .\ntherefore , we propose that reuse of 5ari is helpful in cases that have aggravated bph symptoms or complications of bph .\nthe psa level is also commonly used as a screening tool for prostate cancer , and the level of 4.0 ng / ml or greater , or more recently , greater than 2.5 ng / ml , has predictive value for prostate cancer detection .\npsa velocity also has some predictive potency for detection of the cancer , especially in men with a psa level of 4.0 ng / ml or less .\nthe epithelial cells of the prostate secrete psa , and it is synthesized by androgen regulation . at 1 year of 5ari treatment , the treatment results in an approximate 50% decrease in the psa level compared with the baseline serum level . the use of 5ari changes the psa level , and this may distract the clinician 's attention .\nthe psa level must be multiplied by 2 to maintain its usefulness as a marker .\nthe psa level increases after discontinuation of 5ari because psa is secreted by the epithelial cells of the prostate . in our study , the psa level had decreased 1 year after combination therapy and had increased 1 year after discontinuation of 5ari . in group 1 ,\ntwo patients had continued psa level elevation , and they were finally diagnosed as having prostate cancer .\nthus , regular monitoring of the psa level may be helpful for prostate cancer detection .\nalthough it is not mandatory , we suggest measuring prostate volume by using trus in selected patients with aggravated bph symptoms or a high psa level .\ntrus can provide psa density , which helps clinicians make decisions about further evaluations such as prostate biopsy .\nthe limitations of this study include it being a retrospective review and having a small number of cases .\nprospective randomized clinical trials with a larger number of cases are needed to fully determine the effect of discontinuing 5ari .\nmaximal urinary flow rate is needed to evaluate the changes in urinary symptoms with the use of 5ari .\nlast , our study investigated changes 1 year after the discontinuation of dutasteride , but longer follow - up is necessary to make therapeutic decisions about the effect of 5ari .\nour study showed that withdrawal of 5ari during combination therapy resulted in prostate regrowth and deterioration of luts .\nthe psa level was reduced by the use of 5ari , but discontinuation of the drug resulted in an increase in the psa level . as a result , regular checkup of the ipss and psa level may be helpful for all patients who continue or discontinue use of 5ari .\nwe recommend measuring prostate volume by using trus in selected patients with aggravated bph symptoms or a high psa level .", "answer": "purposeto assess changes in lower urinary tract symptoms ( luts ) , prostate volume , and serum prostate - specific antigen ( psa ) after discontinuation of 5-alpha reductase inhibitor ( 5ari ) combination therapy in patients with benign prostatic hyperplasia ( bph).materials and methodsfrom december 2003 to december 2012 , data were collected retrospectively from 81 men more than 40 years of age with moderate to severe bph symptoms ( international prostate symptom score [ ipss]8 ) . \n the men were classified into group 1 ( n=42 ) and group 2 ( n=39 ) according to the use of 5ari therapy . \n a combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year . \n for the next 1 year , group 1 ( n=42 ) received the combination therapy and group 2 ( n=39 ) received tamsulosin 0.2 mg monotherapy only . \n the ipss , prostate volume , and psa level were measured at baseline and at 12 and 24 months according to the use of dutasteride.resultsdiscontinuation of dutasteride led to significant deterioration of luts , increased prostate volume , and increased psa level . \n the repeated - measures analysis of variance showed that the changes in ipss , prostate volume , and psa level over time also differed significantly between groups 1 and 2 ( p<0.001).conclusionswithdrawal of 5ari during combination therapy resulted in prostate regrowth and deterioration of luts . \n the psa level is also affected by the use of 5ari . \n therefore , regular check - up of the ipss and psa level may be helpful for all patients who either continue or discontinue the use of 5ari .", "id": 249} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nidiopathic demyelinating polyneuropathies are not common in the context of acute kidney injury ( aki ) .\npoems syndrome ( polyneuropathy , organomegaly , endocrinopathy , monoclonal gammopathy , and skin changes ) is a rare disease characterized by the presence of proliferation of plasma cells with mainly lambda - chain restriction and diverse systemic symptoms occurring over several years , meaning that patients typically visit several clinical departments before obtaining the final diagnosis1 ) . kidney dysfunction is not included in the diagnostic criteria of poems syndrome , but aki can be present with other systemic symptoms2 ) .\na 52-year - old korean man was admitted to this hospital because of abdominal distension and diarrhea .\nhe had been well until 4 years ago , when he was diagnosed with cerebral infarct at another hospital .\nhe was a businessman who rarely drank alcohol and had no previous history of medication .\nwhen he was transferred to our hospital 2 years ago , he had the symptom of mild tingling sensation in the left hand .\none and a half years ago , paresthesia of right arm and intermittent difficulties with handwriting developed .\nbrain magnetic resonance imaging ( mri ) with mr angiography showed neither infarct nor vascular stenosis .\nnine months ago , after undergoing health checkups , he was referred to the nephrology , endocrinology , and ophthalmology clinics because of high scr ( 1.52mg / dl ) , elevated thyroid stimulating hormone , and papilledema in both eyes , respectively .\nsince then , he suffered from gradually increasing paresthesia of both feet , progressing to both ankles and to both lower legs .\nhe did not feel muscle weakness , but had some difficulties maintaining balance while walking as well as morning stiffness of both arms .\nnerve conduction studies showed absent bilateral tibial nerve responses , slow motor responses on bilateral peroneal nerves , decreased sensory responses on bilateral sural nerves on the lower extremities , and slow motor and sensory nerve conduction velocities over the right median nerve .\non cutaneous examination , red papules with diameters of 2 to 6 mm , which developed in the previous year , were scattered on the truncal areas .\nhypertrichosis with hyperpigmentation was observed in both hands and lower arms and finger clubbing was present .\nthe pathologic diagnosis of the papules was glomerular hemangioma . computed tomography ( ct ) of the chest and abdomen\nct of abdomen showed multiple small lymph node enlargements around the aorta as well as a small amount of ascites .\na diagnosis of chronic inflammatory demyelinating polyneuropathy was made and therapy with oral prednisolone was initiated . during the next 2 months , weakness in the patient 's legs increased and he developed a limping gait\n. he could not walk on his toes and heels and his perception of vibration decreased in both knees .\nthe test results for syphilis , hepatitis b and c , and hiv were negative .\ntests for autoantibodies such as rheumatoid factor , anti - nuclear antibody , anti - ganglioside antibody , and anti - myelin - associated glycoprotein antibody , were all negative .\ntests for vasculitis and anti - phospholipid syndrome were also negative . the levels of serum complements c3 , c4 and immunoglobulins ig g , a , and m were within normal limits .\na small m - peak was noted ( 0.1 g / dl ) in serum protein electrophoresis ( pep ) and no light chain was detected in urine pep .\nsix months before admission , he was referred to the oncologist for this finding and monoclonal gammopathy of undetermined significance ( mgus ) was a plausible diagnosis .\nthree months after steroid pulse therapy , his muscle weakness and gait improved , but burning paresthesia persisted .\nafter 4 months , the steroid dose had been tapered and stopped . after stopping steroid treatment , he noted rapid progression of muscle weakness ( he could not stand from the floor ) and difficulties with walking and balancing .\nalthough his appetite markedly decreased , his body weight increased by 5 kg and leg edema and abdominal girth increased .\nhe had not taken any nephrotoxic agents including nonsteroidal anti - inflammatory drugs ( nsaids ) .\nlaboratory results showed an increase in scr to 3.21mg / dl and fena and feurea was 0.24% and 12.3% , respectively .\nas abdominal distension increased with ascites he needed therapeutic paracentesis every 4 to 5 days .\nlight microscopic examination revealed renal cortex and medulla containing about 33 glomeruli , one of which was globally sclerotic .\nmost glomeruli showed increase in size and cellularity with mild to moderate endocapillary proliferations with diffuse double contours of capillary walls .\nthere were diffuse interstitial edema and mild interstitial lymphocytes infiltrations with focal tubular atrophy containing hyaline casts destructing of tubular cells .\nimmunofluorescence study did not show any immunoglobulin or complement deposition or staining for kappa and lambda light chain .\nelectron microscopic examination revealed that most glomerular capillary lumina were compromised with diffuse duplications of capillary walls and subendothelial widenings with flocculent materials and mesangial interposition .\nvisceral epithelial cells showed hyperplasia and focal effacement of foot process about 20% of external capillary surfaces .\nbone marrow biopsy showed normal bone marrow cellularity ( 60% ) and a normal ratio of the plasma cells ( 2.3% ) .\nmegakaryocyte hyperplasia was observed and a lymphoid follicle was seen in the bone marrow biopsy .\nimmunohistochemical staining showed that the majority of plasma cells were positive for lambda light chain ( fig .\nthe patient 's diagnosis was almost certainly poems syndrome accompanied by recurrent aki ; however , an additional major criterion was required . upon retrospective review of his previous chest and abdomen\nct , we found osteosclerotic bone lesions in thoracic vertebral bones in the chest ct scan ( fig .\n3 ) . therefore , poems syndrome was diagnosed based on polyneuropathy , monoclonal plasma cell disorder with iga lambda , sclerotic bone lesion , extravascular volume overload , endocrinopathy , hepatomegaly and skin changes , consistent with proposed diagnostic criteria .\nonce the diagnosis of poems had been established , the patient was treated with a 28 days cycle of bortezomib and dexamethasone combination followed by autologous hematopoietic stem cell transplantation ( hsct ) at another hospital .\ntwo months after the procedure , the patient showed a notable clinical improvement including polyneuropathy , normal scr ( 0.80mg / dl ) and mobilization was possible with the aid of a walker .\npoems syndrome is a rare paraneoplastic syndrome resulting from a proliferative monoclonal plasma cell disorder1 ) .\nthe diagnosis of poems syndrome must include two mandatory major criteria of ( 1 ) demyelinating polyneuropathy and ( 2 ) monoclonal plasma cell - proliferation ( almost always type ) .\nin addition , one other major criterion must be present ( any one of the following three features : osteosclerotic bone lesions [ almost always present ] , elevated levels of vascular endothelial growth factor [ vegf ] , or castleman disease ) .\nin addition , at least one of the following seven minor criteria should be met : organomegaly , extravascular volume overload , endocrinopathy ( excluding diabetes mellitus or hypothyroidism ) , typical skin changes , papilledema , or thrombocytosis , polycythemia1 ) . making a diagnosis can be a challenge as the syndrome is rare and can be mistaken for other neurologic disorders .\nthe most prominent symptom of this patient was his progressive sensory neuropathy , followed by the development of motor weakness over a period of 4 years .\npossible differential diagnoses of polyneuropathy and kidney injury include nutritional deficiency such as pyridoxine or thiamine , human immunodeficiency virus - related neuropathy , amyloid , vasculitis , and paraneoplastic syndrome3 ) .\nhis laboratory results for viruses and vasculitis revealed no positive findings and his aki had no definite cause .\nduring the clinical course of this patient , there was no event of renal ischemia caused by nephrotoxic drugs or other systemic hemodynamic change . in the kidney , continuous endothelial injury caused mesangial interposition , mesangial proliferation and finally mesangial sclerosis .\nin addition to the glomerular change , ischemic damage caused by obliteration of arterioles and small arteries was proposed to induce recurrent acute kidney injury2 ) .\nvegf is a potent microvascular permeability - enhancing mediator and a selective mitogen for vascular endothelial cell8 ) .\ntherefore , the vegf produced by plasma cells leads to a decrease in intravascular volume by increasing vascular permeability , which may contribute to prerenal aki5 ) .\nwe might discern from this case that serum and urine pep should be obtained in patients with polyneuropathy and unexplained kidney injury to detect monoclonal gammopathy . however , serum and urine pep of this patient were normal 8 and 6 months ago ( table 1 ) . in poems syndrome ,\nthe median percent of plasma cells in the bone marrow is less than 5% , which is reflected by the small amount of m - protein , and serum pep often can not detect the m - peak1 ) .\ninstead , serum and urine ife should be performed to identify the isotype , as these techniques are three times more sensitive in detecting monoclonal immunoglobulin than serum pep4 ) . in kidney biopsy ,\nimmunofluorescence staining showed no deposition of -light chain and electron microscopy showed no electron - dense deposits .\nthese are quite different findings from other plasma cell disorders that showed kidney damage with deposition of a monoclonal immunoglobulin4 ) .\ninstead , renal pathology of this patient showed extensive endothelial cell injury and evidence of increased extravascular permeability .\nsecretion of vegf from the monoclonal plasma cells in patients with poems syndrome has been suspected to trigger these changes25 ) , but the mechanism remains unknown and must be investigated6 ) .\nin contrast to the pathologic lesions , proteinuria was absent and microscopic hematuria was minimal in this patient , which may reflect a relatively intact glomerular basement membrane structure and podocyte functions .\ntreatment of poems syndrome is directed to target the underlying monoclonal plasma cell disease7 ) and therapeutic strategies for the treatment of multiple myeloma have been reported to show successful patient and renal outcomes and an improvement in morbidities related to treatment67 ) .\nas this patient showed bone marrow involvement , he received systemic chemotherapy and had autologous blood stem cell transplantation .", "answer": "poems syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction . here \n , we report a case of poems syndrome with recurrent acute kidney injury ( aki ) . a 52-year - old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine . \n the patient was finally diagnosed with poems syndrome on the basis of fulfilling the two mandatory major criteria ( polyneuropathy and monoclonal gammopathy ) , one other major criterion ( sclerotic bone lesion ) , and several minor criteria . \n a renal biopsy was performed to clarify the cause of aki and showed membranoproliferative glomerulonephritis - like lesions with mesangiolysis and endothelial cell injury . \n this case illustrates that renal manifestations , not included in the diagnostic criteria for poems , can be apparent before various other systemic symptoms .", "id": 250} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin pregnant women with mechanical heart valves , the frequency of valve thrombosis increases due to pregnancy - related hypercoagulability . therefore , effective anticoagulation is critical in pregnant patients with mechanical heart valves but remains problematic because both oral anticoagulation and heparins have been associated with important fetal and maternal side effects ( 1 ) .\ncoumarin derivatives are anticoagulants of choice for mechanical heart valves , but they cross the placenta and are associated with coumarin - induced fetal loss or embryopathy ( 1 - 3 ) .\nunfractionated heparin ( ufh ) provides an alternative therapy that avoids fetal side effects , however , the use of ufh is associated with increased maternal thromboembolic and bleeding complications ( 1 , 4 , 5 ) . low molecular weight heparin ( lmwh ) may be more advantageous than ufh ( 6 ) , and appears a good alternative . however , little clinical information and no reliable data are available regarding its efficacy and safety . no consensus has been reached about optimal antithrombotic therapy in pregnant patients with a mechanical heart valve .\ncoumarins are contraindicated in pregnancy in north america due to fetal concerns , but european experts have recommended low dose coumarins ( less than 5 mg daily ) throughout pregnancy given a very low frequency of fetal anomalies ( 2 , 3 ) .\nreports of lmwh use began to appear , and many physicians now use lmwh because of its good safety profile for both mother and baby ( 7 - 10 ) .\nhowever , treatment failures have been reported ( 11 , 12 ) , and no lmwh has been licensed for use in pregnant patients with mechanical heart valves .\navailable published data regarding the efficacy and safety of lmwh in this clinical setting have been derived from small case series , and usually enoxaparin has been used . here\n, we report our experience of nadroparin treatment , and its associated pregnancy outcomes and maternal complications .\nbetween 1997 and 2005 , 31 pregnancies were analyzed retrospectively in 25 women with mechanical heart valves .\nbasic characteristics and previous operative data are listed in table 1 . in 23 of these 31 pregnancies ,\nnadroparin was used as an anticoagulant during the first trimester with given informed consent , concerning the risks and benefits of lmwh .\nothers were anticoagulated with coumarin derivatives ( cmd ) with or without aspirin due to unawareness of pregnancy until the first trimester , or because of refusal or poor compliance on self - injected lmwh . in the lmwh - treated group ,\nwhen pregnancy was confirmed , coumarins were stopped and changed to subcutaneous nadroparin ( 7,500 u , twice daily ) , from 6 weeks to 12 weeks of gestation .\naspirin , at 100 mg / day , was also administrated throughout the pregnancy . at gestation week 38\n, women were scheduled for labor induction and changed to nadroparin to avoid the delivery of an anticoagulated fetus . after establishing labor\n, we carefully checked for hemorrhages and other complications , and babies were examined for congenital anomalies and weight . in the cmd - treated group , coumarins and aspirin were continued throughout the pregnancy and the target international normalized ratio ( inr ) was maintained between 2.5 to 3.5 .\ncoumarins were changed to nadroparin before 2 weeks prior to the expected delivery date to avoid fetal bleeding complications during delivery .\npregnancy outcomes , namely , numbers of healthy babies , fetal anomalies , fetal losses , and maternal complications , including thromboembolism or bleeding , were analyzed . to evaluate the efficacy and safety of lmwh , eight pregnancies , maintained using coumarins throughout pregnancy , were compared .\ndata were analyzed using spss for windows version 10.0 software and compared using the student 's t - test , at a level of significance of p<0.05 .\nno maternal death or bleeding complication occurred in either the lmwh - treated group or the cmd - treated group .\nfrequencies of maternal thromboembolism were not different between the two groups ( table 2 ) . a maternal transient ischemic attack ( tia ) occurred in one case in each group , and both patients had previously undergone mitral valve replacement .\nprosthetic mitral valve thrombosis occurred in three pregnancies , two in the lmwh group and one in the cmd group ( table 3 ) .\nthe two of these three patients underwent redo surgery , and other patient was managed on thrombolytic therapy .\nnumbers of live born and healthy babies were higher in the lmwh group ( table 4 ) . in both groups , two babies had low birth weights of 2.1 kg and 2.4 kg , but were otherwise healthy . in the cmd group , one baby had hydrocephalus . however , the frequency of fetal loss including therapeutic abortion and stillbirth were significantly higher in the cmd group .\ntwo fetal losses occurred in the lmwh group , both occurred in cases of maternal valve thrombosis .\nfour fetal losses occurred in the cmd group , and one of these involved maternal valve thrombosis .\nthis study demonstrates that lmwh - based therapy is superior to coumarin therapy in pregnant women with a prosthetic heart valve , and that the use of nadroparin during the first trimester with 100 mg of aspirin throughout pregnancy could be a safe and effective protocol for thromboprophylaxis in these women .\nrecent recommendations , published in 2004 as part of the 7th american college of chest physicians ( accp ) consensus on antithrombotic therapy ( 12 ) , included the following three regimens : 1 ) aggressive adjusted - dose lmwh throughout pregnancy ; 2 ) adjusted - dose ufh , throughout pregnancy ; or 3 ) either lmwh or ufh between 6 and 12 weeks and close - to - term only and the use of cmd at other times .\nour protocol was similar to the third regimen , but we also administered aspirin ( 100 mg daily ) throughout pregnancy to reduce coumarin dosages and the risk of thromboembolism .\nthe overall frequencies of maternal thromboembolism , including valve thrombosis , were similar in both groups , but the frequencies of live and healthy baby births were higher in the lmwh group .\nthese results demonstrate that lmwh - based therapy is a good alternative to coumarins , because it has similar anticoagulation effects with lower fetal side effects .\nexposure to coumarins during the second part of the first trimester is associated with fetal loss , primarily due to spontaneous abortion or coumarin - induced embryopathy .\nthe reported frequencies of coumarins - related embryopathy vary for debatable reasons ( 14 , 15 ) , a recent study suggested that coumarin risk is dose related and that adverse effects occur mainly in women taking > 5 mg daily .\n, the target inr was maintained with less than 5 mg of coumarins in all patients in the cmd group ; however , a half of these lost their babies due to abortion or stillbirth .\nour results represent only observational data , and the effect of dose - related embryopathy remains uncertain .\nlmwh does not cross the placental barrier and offers potential advantages compared with ufh in terms of better safety profile with less thrombocytopenia , less bleeding , less osteoporosis with prolonged treatment , a more predictable and rapidly reached anticoagulant effect , and the possibility of self - administration of anticoagulant therapy without laboratory monitoring\n. however , treatment failures have been reported , and the use of lmwh for pregnant women with mechanical heart valves has become controversial due to small numbers of patients and a lack of accurate postmarketing data ( 16 ) .\na recent review of 81 pregnancies in 75 women treated with lmwh reported an 8.6% rate of valve thrombosis ( 17 ) , and found that appropriate dose adjustments could reduce the frequency of thromboembolism .\nthe 7th accp recommendations call for the use of lmwh at levels that achieve peak anti - factor xa values of around 1.0 u / ml ( 12 ) . a recent prospective study with deltaparin reported that dosages based on body weight were inadequate to maintain a therapeutic level of lmwh in pregnancy ( 18 ) .\nour data demonstrate that valve thrombosis occurred in 2 patients treated with nadroparin ; a prevalence of 8.7% .\nunfortunately , we did not monitor anti - xa levels during nadroparin administration , and thus , we can not conclude that valve thrombosis is associated with an inadequate nadroparin dose .\nfurther studies , with sufficient statistical power , are required to clarify the clinical significance of anti - xa levels . in conclusion , despite the retrospective design of the present study , it might be worth to mention that lmwh appears a safe and effective substitute for any other anticoagulants in pregnant women with mechanical heart valves .\nwe have experienced that pregnancy outcomes are acceptable with lmwh , but that its efficacy for preventing valve thrombosis remains uncertain .\nfurther studies are needed in order to establish appropriate management protocols for pregnant women with mechanical heart valves .", "answer": "no definitive recommendation is available concerning optimal antithrombotic therapy in pregnant women with a mechanical heart valve . the purpose of the current study was to evaluate the clinical results of nadroparin treatment with respect to pregnancy outcome and maternal complications . from 1997 to 2005 , 31 pregnancies were reviewed in 25 women . \n nadroparin ( 7,500 u , twice daily ) was used in 23 pregnancies between 6 and 12 weeks of gestation and close - to - term only , and coumarin derivatives were used with aspirin at other times . \n eight pregnant women treated with coumarin derivatives throughout pregnancy were compared to evaluate the safety and efficacy of nadroparin . \n no maternal death or bleeding complication occurred in either of the two groups , and frequencies of maternal thromboembolism including valve thrombosis ( 8.7% vs. 12.5% , p>0.05 ) were similar . \n however , the frequencies of live born ( 91.3% vs. 50% , p=0.01 ) and healthy babies ( 90.4% vs. 25% , p<0.01 ) were significantly higher , and the fetal loss rate was significantly lower ( 8.7% vs. 50% , p=0.01 ) in the nadroparin - treated group . regarding the efficacy and safety of antithrombotic treatment in pregnant women with prosthetic heart valves , nadroparin treatment during the first trimester is an acceptable regimen and produces better results than coumarin derivatives .", "id": 251} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhepatocellular carcinoma ( hcc ) is a common malignancy and is now one of the major causes of death in asian countries . generally , hccs are often asymptomatic , but fatigue , abdominal distention and low - grade fever\nhowever , fever as a primary symptom in hcc is relatively rare . additionally , high crp in laboratory results is also rare .\nhcc with pyrexia has been reported only in a few studies [ 24 ] and the cause of pyrexia has remained unknown . recently , increased production of proinflammatory cytokines and chemokines , such as interleukin-1 ( il-1 ) , interleukin-1 ( il-1 ) , interleukin-6(il-6 ) , interleukin-8(il-8 ) , and tumor necrosis factor- ( tnf- ) have been reported to be febriferous in acute and chronic inflammatory disease [ 5 , 6 ] . these cytokines are produced by immune cells including various populations of lymphocytes macrophages and other cells . among the proinflammatory cytokines ,\nil-8 is a neutrophil chemotactic factor and involved in tumor proliferation and migration , angiogenesis in malignant tumors .\nthis is often accompanied by rapid growth and poor prognosis in malignant tumors [ 713 ] . \nwe herein discuss a case of hcc accompanied by prolonged spiking fevers , which disappeared after tumor resection .\na 50-year - old man with a history of liver dysfunction was admitted to iizuka hospital with the chief complaint of a prolonged fever and general fatigue in october , 2005 .\nhematological laboratory data on admission were as follows : wbc 9670/ l , alp 552 u / l , crp 16.7 mg / dl , and afp 11.1 ng / ml .\nhbs - antigen was positive ( table 1 ) . a computed tomography ( ct ) showed a peripherally enhanced low density mass 7.5 cm in diameter , which located in segment 6 in the right lobe of the liver ( figure 1(a ) ) .\nthe tumor was accompanied with tumor thrombus to the posterior branch of portal vein ( figure 1(b ) ) .\nceliac angiography showed this lesion was hypervascular ( figure 1(c ) ) and portal vein tumor thrombus in posterior segment was observed in the portal phase ( figure 1(d ) ) . \npatients have chronic hepatitis b and then tumor was hypervascular and accompanied with portal thrombus , which is the feature of hcc , therefore a preoperative diagnosis was made as hcc with portal vein thrombus and nonsteroidal anti - inflammatory drugs were used to reduce the fever .\na single nodule of disseminated cancer cells was found near the posterior segment on the abdominal wall during the operation .\nposterior segmentectomy of the liver and thrombectomy including the dissemination was performed . on the cut section ,\nthe noncancerous liver tissue showed a moderate chronic inflammatory infiltrate in the fibrous stroma , diagnosed as liver fibrosis .\nimmunohistochemical stain of il-8 was performed with paraffin embedded sections of liver tissue using mouse monoclonal antibody at dilutions of 1 : 100 ( assay designs , ann arbor , usa ) .\nthe subsequent reaction was performed by the peroxidase labeled streptavidin - biotin technique using histofine sab - po kit ( nichirei , tokyo , japan ) .\nil-8 was observed in the cytoplasm of cancer cells ( figure 3(b ) ) . \nafter the tumor resection , fever disappeared and crp dropped gradually from 16.7 to 2.7 , but the patient had recurrence with multiple liver metastasis and pleuritis carcinomatosa and died on february 2 , 2006 , 79 days after the operation .\nin 1991 , okuda et al . reported five patients with hcc and pyrexia , for an incidence of less than 1% , in japan .\nhe also mentioned that very poorly differentiated sarcomatoid hcc may frequently appear with pyrexia and leukocytosis mimicking liver abscess . in 1995 , hayashi et al . reported hcc with pyrexia\nlaboratory data revealed high crp . nevertheless , in both case reports , the mechanism of a fever was not revealed . in our case ,\nthe sarcomatoid change of the cancer cell was not detected , only poorly differentiated hcc . \nit is well known that cancer cells produce humoral factors and cause the paraneoplastic syndrome . among the clinical symptoms and laboratory data , fever and high crp ,\nwhich is not commonly observed in the patients with hcc , is suspected to be due to humoral factors , especially inflammatory cytokine .\nil-8 is a proinflammatory cytokine whose principal role in infection and inflammation appears to be the recruitment and activation of circulating and tissue neutrophils to the site of tissue damage .\nit has been demonstrated that il-8 is produced by a wide variety of cell types in vitro , including endothelium , monocytes , eosinophils , astrocytes and keratinocytes . in sepsis patients , for example ,\nil-8 concentrations have been reported as being markedly elevated at diagnosis and remaining high during the course of the illness .\nthis symptom is induced by many humoral factors , including il1 , il-6 , il8 and tnf. zampronio ar reported that il-8 induced fever by prostaglandin independent mechanism .\nil-8 resulted in a dose - dependent increase of crp , a decrease in the production of transferring and prealbumin .\ntherefore , il-8 is related to pyrexia in parts , not all . in other cancer ,\nwe examined by immunohistochemical staining of il-8 and tumor tissue stained positive for il-8 in this case .\nakiba et al . reported that a high il-8 level in hcc had a significantly higher frequency of portal vein invasion and venous invasion and bile duct invasion . in vitro\nreported il-8 production was enhanced progressively with escalating severity of hepatitis and the development of hcc and the level of il-8 were significantly increased in patients with advanced hcc with distant metastasis , and then this leads to poor prognosis .\nren et al . reported serum il-8 level was correlated with tumor size and tumor stage , and then il-8 level was a significant prognostic factor in terms of disease - free survival and overall survival .\nadditionally , elevated il-8 levels in the drainage vein of colorectal cancer are related to the occurrence of hepatic metastasis .\nthis case presented portal vein tumor thrombus , bile duct invasion , intrahepatic metastasis , peritoneal dissemination , early tumor recurrence , rapid tumor regrowth and finally a poor prognosis .\nin fact , all patients with il-8 production do not have a high fever , the serum concentration of il-8 or the degree of neutrophil infiltration will be concerned with pyrexia . in many cancers such as esophageal cancer , gastric cancer and colorectal cancer ,\nserum crp was known as a prognostic indicator [ 2023 ] . in particular , some reported that serum crp levels indicated a poor prognosis in hcc patients and portal vein invasion was significantly higher in the serum crp - positive group [ 24 , 25 ] . according to the in vitro previous studies , cultured hcc can produce crp that is regulated in part by proinflammatory cytokines , such as il-6 , il-8 and tnf- [ 18 , 26 , 27 ] . among the many proinflammatory cytokines , recent report il-6 mediates cell cycle arrest in hepatocellular carcinoma through a stat 3-dependent pathway\nhcc produce proinflammatory cytokines such as il-8 by autocrine or paracrine , which lead to crp production and inflammatory cascade or tumor progression . \nin this report we discussed a patient who had poorly differentiated hcc with pyrexia and high crp .\nil-8 production was histologically revealed in this case and may have contributed to the high fever , high inflammatory reaction and poor prognosis .", "answer": "we discuss a patient who had poorly differentiated hcc with pyrexia and high crp in laboratory data , which are not commonly observed in the usual hcc . \n a 50-year - old man with a history of liver dysfunction was admitted with a chief complaint of a prolonged fever and general fatigue . \n preoperative diagnosis was hcc with portal vein tumor thrombus . \n posterior segmentectomy of the liver and thrombectomy was performed . \n rapid tumor recurrence occurred after surgery , and he died 79 days after the operation . \n immunohistochemical stain of hcc in this patient revealed the production of proinflammatory cytokine , interleukin-8 ( il-8 ) . \n il-8 production may have contributed to the high fever , high inflammatory reaction , and poor prognosis in this case .", "id": 252} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe treatment of lymphoma depends on the type , location and stage of the disease .\nthe majority ( 50%90% ) of oal is low - grade mucosa associated lymphoid tissue ( malt ) lymphoma . according to the world health organization modification of the real classification ,\nthe other 4 main types of oal are follicular cell , mantle cell , diffuse large b cell ( dlbcl ) and lymphoplasmacytic lymphoma .\nthey are all b cell , non - hodgkin s lymphoma , the subtype derived from various stages of b cell maturation .\nthe new classification of lymphoma is dependent on histological , immunophenotypic and molecular genetic analysis .\nhodgkin s lymphoma does not affect the ocular adnexal structures unless there is widespread systemic involvement or a history of previous systemic hodgkin s lymphoma . according to the ann - arbor staging system lymphoma confined to the orbit\nis designated as stage i , involvement of adjacent structures ( sinuses , tonsil and nose ) is stage ii .\nstage iii is abdominal nodal disease below the diaphragm and iv by definition refers to disseminated involvement of one or more extra - nodal sites ( eg , liver , bone ) and e is used when there is a local extra - nodal extent ( eg , ie , iie , iiie and i ve ) .\nthe grading system is similar to nodal lymphomas . broadly speaking , oal with systemic involvement\nrequires systemic treatments whereas low - grade ( emzl or follicular cell ) lymphoma localized to the eye can be very successfully managed with local treatments such as cryotherapy , surgical excision or external beam radiotherapy . when considering local treatment it is important to exclude bilateral ocular involvement . even in the absence of clinical signs\nstaging investigations should include full blood count , hepatic enzymes including ldh , ct abdomen , chest and pelvis , mri or ct of the orbits , and a bone marrow biopsy and aspirate .\nthis is only appropriate for low - grade lymphoma localized to the conjunctiva or orbit with no systemic involvement .\nsurgical excision or cryotherapy is most appropriate for localized stage 1 conjunctival emzl / malt lymphoma.1 this is not curative treatment but can control local disease and relieve local symptoms .\ntanimoto et al2 reported very good local control of stage 1 malt lymphoma following biopsy or surgical resection alone .\npatients were followed for a median of 7.1 years , 69% of patients did not require any further treatment .\nthe estimated overall survival rates were 94% at 10 years and 71% at 15 years.2 although , patients should be closely followed for recurrence , histological transformation of the tumor and long - term systemic manifestations of lymphoma .\nthis has been the mainstay of treatment for localized oal for many years with excellent control rates .\ncentral nervous system prophylactic radiotherapy is not required as metastatic intraocular or brain involvement is rare.3 the dose of radiation is tapered according to the grade of the lymphoma , 28 to 36 gy for low - grade lymphoma and 30 to 40 gy for high - grade .\nemzl , lymphoplasmacytic and follicular cell lymphoma are considered low grade , whereas dlbcl and mantle cell are high - grade lymphomas .\nfive - year local control rates for emzl and follicular lymphoma after a dose of more than 30 gy reach 100%.4 however , high rates of delayed systemic recurrence suggest long - term follow up studies are required to assess the true benefit of radiotherapy.5 there is ongoing debate about use of lens shielding radiotherapy to protect the lens from cataract formation .\nsome studies show no effect on local recurrence , whereas in others all recurrences have occurred in patients whose lenses were shielded.6,7 partial orbit volume irradiation leads to unacceptable incidence of intraorbital recurrence and is presently not recommended .\nocular complications , including dry eye and cataract are frequently reported in patients that have long - term follow up.8 these localized complications need to be kept in mind by the treating oncologist .\nifn - alpha has been used for the treatment of systemic lymphoma for more than 20 years .\none study treated 5 patients with intralesional ifn - alpha using an intensive protocol.9 an initial complete response was seen in all patients with stage i oal , one patient with more advanced disease at presentation ( stage iia ) died from systemic lymphoma .\nlong - term follow up studies are required to assess the value of this treatment .\nrituximab is a monoclonal antibiotic against cd20 positive b cells , which is being considered as an alternative first line treatment for localized cd20 positive oal to avoid the ocular complications of radiotherapy .\nantibody - induced destruction of cd20 positive b cells can occur by apoptosis , complement mediated cytolysis and antibody - dependent , cell - mediated cytoxicity .\nrituximab has also been used as monotherapy for localized emzl / malt , in some cases complete regression can be achieved .\ninitial responses are encouraging but the efficacy of rituximab is lower than that reported for gastric malt lymphoma,10 as long - term distal relapse is seen in 50% of cases . very few case series are published on the effect of single agent rituximab on ocular malt / emzl .\nferreri and associates achieved regression of malt lymphoma using first line single agent rituximab in all 5 newly diagnosed patients ; however early relapse was seen in 4 of the 5 patients.10 therefore , close follow up intervals are required to detect early relapse when rituximab is used alone .\nrituximab was not successful for the treatment of local relapse.10 greater success is achieved when rituximab is used in combination with chemotherapy .\nrituximab and chlorambucil were used as first - line therapy for 9 patients with newly diagnosed emzl .\ntreatment achieved complete remission in 89% with a median follow up of 2 years.11 first - line chemotherapy is often treatment of choice for mantle cell oal , as a high proportion of patients have systemic involvement at presentation .\nencouragingly , rituximab containing chemotherapy for mantle cell oal had a significantly better 5-year survival than patients receiving chemotherapy alone ( 83% overall 5-year survival verses 8%).12 combination treatment with rituximab and chemotherapy or radioimmunotherapy may achieve a more durable local response and improve patient survival.1113\nchemotherapy is reserved for treatment of oal when there is systemic involvement , except for the high - grade dlbcl when systemic chemotherapy is first - line treatment even for stage i disease .\nmore recently chlorambucil and the purine analogs fludarabine , clardarabine and pentostatin have also been used .\nthe extranodal lymphoma study group ( ielsg ) is currently recruiting patients to a clinical trial investigating the role of rituximab alone or in combination with chlorambucil for malt lymphoma ( ielsg # 19).14\nnovel mechanisms of tumor pathogenesis have related lymphoma to infection leading to new approaches to diagnosis and treatment .\nchronic antigen stimulation may result in an abnormal lymphoproliferative response that ultimately develops into lymphoma .\nthis association is most profound for gastric malt cell lymphoma , which is related to chronic gastritis from helicobacter pylori infection in more than 90% of cases.15 h. pylori has been isolated from ocular lymphoma specimens .\nhowever , h. pylori eradication is not effective treatment for oa malt lymphoma.16 chlamydia psittaci infection has also been linked to oal .\nferreri and associates17 identified c. psittaci in 80% of italian oa malt lymphoma specimens . in korea , c. psittaci was isolated in 78% of oa malt lymphoma specimens.18\nsubsequent reports from south florida , new york state , chicago , netherlands , japan and france failed to identify dna for c. psittaci in any of their oa malt lymphoma specimens.1924 there is wide geographical variation in the prevalence of c. psittaci infection in oa malt lymphoma specimens.25 of the european countries studied , the lowest rate of infection ( 12% ) was present in the uk .\nresults following first line antibiotic treatment are variable.26 abramson and coworkers27 documented a clinical response following antibiotic treatment in 3 patients with oa malt lymphoma .\nferreri and associates28 recorded an objective response following oral doxycycline in 4 out of 9 patients with c. psittaci positive oa malt lymphoma .\nalthough , grunberger and associates29 were unable to replicate these results . in a multicenter prospective trial ,\n27 patients with ocular adnexal malt lymphoma were treated with oral doxycycline . c. psittaci dna positive cases had an overall response rate of 64% , the response was of short duration.30 a clinical response\nwas also seen in 38% in c. psittaci dna negative cases.30 lack of response to antibiotic therapy may be a reflection of the biological and genetic heterogeneity of this disease .\nthe extranodal lymphoma study group ( ielsg ) has activated a prospective trial ( ielsg # 27 ) into oal to explore the role of antibiotic treatment and to identify potential infectious agents.14 in summary , advances in our knowledge of the immunophenotypic and genetic alterations in lymphoma cell lines have led to a better understanding of the pathogenesis of the disease .\nthe interplay between a possible infective agent and the immune response has allowed a new wave of treatment possibilities .\nstaging the patient at diagnosis guides subsequent management and local treatments should be reserved for localized disease .\nhowever , the practical approach to the patient remains first do no harm and with this in mind ocular oncologists are tempted to administer an initial trial of oral antibiotics for stage 1 malt lymphoma .\nalthough , general blanket treatment with antibiotics should be discouraged unless there is proof of an infective agent .\nwe recommend a diagnostic biopsy with immunophenotyping and genetic analysis to determine the grade of the lymphoma combined with pcr analysis to determine the presence of an infective agent . if h. pylori or c. psittaci infection is found a trial of oral doxycycline ( 100 mg twice daily for 3 weeks )\nwe have also seen some early impressive responses to systemic rituximab ( weekly intravenous infusion over 6 weeks ) . however , close follow up is required as others have reported early local relapse with rituximab alone.10 at present , despite the ocular side effects , localized radiotherapy still remains the standard first - line treatment for stage i low - grade oal .", "answer": "most lymphomas that involve the ocular adnexal structure are low grade , b cell , non - hodgkin s lymphomas . \n the treatment depends upon the grade and stage of the disease . \n high grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade ( extranodal marginal zone lymphoma ) can be successfully managed with local radiotherapy . \n chlamydia psittaci infection is associated with low grade ocular lymphoma ; however there is wide geographic variation in the strength of this association . \n blanket antibiotic therapy is not advised unless there is proof of an infective agent . \n the monoclonal antibody , rituximab , may be successful for cd20 positive lymphoma , although it is likely that rituximab will have better long - term results when used in combination with systemic chemotherapy .", "id": 253} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe femoral head often leads to healing complications , while the more predictable prosthetic replacements are associated with poorer function and significant complications .\nthe treatment of these fractures depends on the age of the patient , fracture displacement , bone quality , timing of surgery and activity level of the patient .\ndisplaced fractures in healthy , active patients are best treated by reduction and internal fixation .\nthere are however , complications unique to femoral neck fractures which are almost impossible to predict . non - union and avascular necrosis\nnon - union usually can definitely diagnosed within a year of fracture fixation with the same being achieved within 3 months at times . after non - union has been established , intervention is inevitable .\nthe decision to proceed in the management of failed fixation is based on the careful consideration of various factors . in young patients\nrevision internal fixation with cancellous or muscle pedicle bone grafting ( vascularised bone graft ) or an osteotomy results in useful outcome .\nwe report a case of non - union of the fracture of the neck of the femur , who refused additional procedures after his non - union had been established .\nthe study conforms to the declaration of helsinki and was approved by the institutional ethical board .\na 38-year old male businessman reported to the out door department of our hospital with a history of a fall from height .\nclinical and radiological examination revealed a displaced fracture of the neck of the femur which was graded as garden type 4 ( fig .\nthe patient was operated within 24 h. intraoperatively the garden alignment index was used as a yardstick of acceptable reduction .\nthe fracture was fixed with 3 ao 6.5 mm cannulated screws in an inverted triangle .\nonward the patient complained of persistent but mild groin pain on ambulation which was assisted .\nthe patients conservative line was continued till 1 year when his symptoms continued and radiologically there was no progress . at this point\ntwenty - six months into the post operative followup the patients pain subsided and radiographs started showing signs of union . a radiograph taken 32 months after the fixation showed full union .\nnon - union after femoral neck fracture can be defined as a lack of radiographic evidence of union 6 months after the fracture .\ndelayed or non - union often manifests as continued pain with weight bearing beyond 3 months post fixation .\nincidence of non - union of femoral neck fractures has been reported to be between 2 and 22% and generally becomes apparent within 1 year [ 69 ] .\n3radiograph at 32 months depicting union garden 4 type fracture of the neck of the femur showing persistent non - union at 2 years radiograph at 32 months depicting union anatomical reduction and rigid internal fixation are the two important surgeon controlled factors that may contribute to outcome .\nthe preferred treatment for symptomatic non - unions in the elderly is prosthetic replacement . in the young active patients ,\nif failure is due to technical errors , revision open reduction and internal fixation may be adequate .\nour case demonstrates that as long as the implant is holding and the patient is regularly followed up good results might be expected in cases as far as 32 months into the post fixation period .", "answer": "fracture of the femoral neck continues to be a vexing clinical and therapeutic challenge for the orthopedic surgeon . \n the fracture has a propensity for non - union and avascular necrosis . \n it is a challenge for the orthopedic surgeon to decide when to intervene in a case with non - union where the implant continues to be in place . \n we present a case with persistent clinical and radiological non - union signs where the fracture eventually united after 32 months . \n the case bolsters the view that a continued conservative regime might entail good results in such situations .", "id": 254} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 78-year - old woman presented with weakness , fatigue and hemoglobin of 8.3 g / dl , to another clinic in september , 2009 , and she was given erythrocyte suspension replacement .\nshe had regression in her existing complaints with blood replacement therapy , but after one month , same complaints reappeared with a low hemoglobin value and she was referred for further investigation to the outpatient clinic of hematology of our university faculty of medicine . her hematologic parameters ar that time were as follows : white blood cell count of 6390/mm , neutrophils 3785/mm , hemoglobin 8.1 g / dl , mean corpuscular volume ( mcv ) 95 fl , and platelets 211.000/mm . with the provisional diagnosis of myelodysplastic syndrome due to an isolated anemia unrelated to nutritional status , bone marrow aspiration biopsy was performed .\nher bone marrow aspiration showed normal cellularity ; and biopsy revealed increase in the number of megakaryocytes , signs of dismegakaryopoiesis , minimal dysplasia in erythroid series , and normal morphology in myeloid series . upon conventional cytogenetical studies\nshe had been lost - to - follow up for approximately a year and during that time she had received a total of 4 units of erythrocyte suspension , and erythropoietin treatment was started .\nhowever , erythropoietin treatment discontinued because she did not respond to the maximum dose of 10.000 iu three times a week .\nshe did not attend to her follow - up visits regularly and in the mean time she had transfusions monthly at another clinic .\nsince her transfusion dependency increased , she was considered for lenalidomide treatment in april , 2013 .\nafter 10 days of treatment , her liver enzymes increased more than 3 times of normal values and she had thrombocytopenia ( platelet count : 38.000/mm ) then her treatment was postponed for two weeks she restarted lenalidomide treatment at daily doses of 5 mg after liver enzymes and platelet counts returned to normal . during\nfurther follow - up , increase in liver enzymes and severe thrombocytopenia were not detected ; her hemoglobin value increased and transfusion dependency was not observed ( figure 1 ) .\nin myelodysplastic syndrome , interstitial deletion in the long arm of chromosome 5 is a common cytogenetical abnormality seen in 16 - 28% of the patients .\nit is characterized by hypoproliferative anemia and normal megakaryocytes with hypolobated nuclei or increased dysplastic megakaryocytes in bone marrow [ 7 , 8 ] .\nmost of the patients are transfusion - dependent because endogen erythropoietin production is usually increased .\none of the major problems during the progression of the disease in transfusion - dependent mds patients is the iron overload secondary to transfusion and the dependency for chelation therapy to treat iron overload .\nthe immunomodulatory drug lenalidomide that has additional benefits in the regulation of erythropoiesis , inhibition of angiogenesis , and reorganization of erythroid production , targets the mds clone directly [ 9 , 10 ] .\nthis syndrome is rarely seen ; therefore , there is not enough data about isolated 5q - syndrome as well as lenalidomide therapy in our country .\nisolated 5q - syndrome presents with normal or increased thrombocyte counts in peripheral blood and anemia with frequent transfusion replacement dependency . in clinical studies\nlenalidomide provided long term blood transfusion independency and erythroid response in patients with low- risk del(5q ) and without del(5q ) . in a phase ii study of low- risk del(5q ) patients ; after 24 weeks , evaluation of erythrocyte response showed that 67% of the patients with 5q deletion who were treated with lenalidomide became transfusion independent . in low- risk\n5q deletion mds patients , daily doses of 10 mg for 21 days are used , and repeated with 28 day - intervals that can be modified if needed . in order to evaluate the response ,\nadverse events can be easily overcome with dose modifications . in clinical studies , thrombocytopenia and leukopenia\nare frequently observed but these adverse reactions usually appear during the first 8 weeks of treatment .\ntherefore , weekly clinical follow - up at the beginning of the therapy is recommended .\nless often adverse events of fatigue , rash and diarrhea can be noted . in conclusion , in isolated 5q - syndrome which is a mds subgroup and characterized by transfusion dependency ; lenalidomide can decrease transfusion dependency with a tolerable adverse event profile that can be overcome with dose modifications .\nassessment of all prevalent cases in our country will be helpful to reveal the efficacy and adverse event profile of lenalidomide .", "answer": "5q - syndrome is a special subgroup of myelodysplastic syndrome in terms of follow - up and treatment . \n lenalidomide is an immunomodulatory drug that is frequently used in the treatment of multiple myeloma . \n some clinical studies have shown that lenalidomide treatment is effective in 5q syndrome and significantly decreases the transfusion dependency in these patients . in this paper \n , we would like to share a dramatic response of lowered transfusion dependency after treatment with low - dose lenalidomide in a patient who received myelodysplastic syndrome diagnosis and isolated 5q anomaly in our clinic .", "id": 255} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlangerhans cell histiocytosis ( lch ) refers to a clonal , neoplastic expansion of langerhans cells .\nstimulation by tumor necrosis factor and granulocyte - monocyte colony - stimulating factor has been implicated in the pathogenesis ( as has human herpesvirus 6 ) .\nit most commonly affects children between the age of 1 and 4 , although cases have been described in all age groups ; the incidence in pediatrics has been estimated at 25 per million / year .\nit is exceptional for lch to present with brain involvement as the sole presenting symptom .\nthis complication is reported as occurring in 14% of patients with multisystem disease , typically 520 years from the initial diagnosis .\nhe developed depression , anxiety and agitation , which led to his retirement from construction work .\nshortly thereafter , he developed episodes described as hyperventilation , lasting from seconds to minutes , mostly in the morning , which were followed by confusion and a severe pounding headache affecting the whole head , both of which lasted for hours .\none year prior to presentation , his family described personality changes ( it was hard for them to characterize this further ) and worsening confusion , particularly over the preceding 3 months .\nthree months before presentation , he developed weakness of the right leg , which had been slowly progressing since .\ntwo weeks prior , it became so bad that he needed help walking . at this time\n, he also noticed weakness of the right arm and slurring of speech , which led him to seek medical help . he had been diagnosed with peripheral arterial disease ( claudication in his left leg ) 4 months prior to presentation , and paroxysmal atrial fibrillation 1 month prior\nhis initial review of systems revealed that he was anorexic and had lost 30 lb over the last 2 years .\nhe also complained of a loss of libido and an occasional shortness of breath when walking . on initial exam ,\nhe was unable to sustain upward gaze ; vertical saccades were followed by a slow downward drift , then a compensatory saccade .\nhe had a weakness of the right side of his face , sparing the forehead .\nhe was weak throughout , with strength of 4/5 on his right side in an upper motor neuron pattern with signs of spasticity ; babinski 's reflex was present on this side .\nhis initial complete blood count , comprehensive metabolic panel , serum protein electrophoresis and folate were normal apart from a white cell count of 13 10/l ( 95% neutrophils ) and platelets of 570 10/l .\nhis sodium was initially normal , but , during his admission , it was generally in the range of 145160 mmol / l .\nmg / l ( < 10 ) , and the erythrocyte sedimentation rate 60 mm / h ( < 20 ) .\nhe was hypothyroid with a thyroid - stimulating hormone ( tsh ) level of 5.6 iu / ml ( < 4.9 ) and a free t4 of 0.6 ng / dl ( > 0.7 ) .\nhe had hypogonadism ( presumably secondary ) with total testosterone of < 20 ng / dl ( > 200 ) .\na lumbar puncture was done shortly after admission , showing 4 red cells , 9 white cells ( 56% lymphocytes , 43% macrophages ) , and a protein level of 45 mg / dl ( < 35 ) .\noligoclonal bands were absent and cytology showed no signs of malignancy . shortly after admission , a complete serum paraneoplastic panel was sent ; this was negative .\nthe antibodies reported were : anti - neuronal nuclear types 13 , anti - glial nuclear type 1 , purkinje cell types 12 and type tr , amphiphysin , crmp-5-igg , striatal , t / q and n - type calcium channels , ach receptor - binding , ach receptor ganglionic and neuronal voltage - gated k channels .\nmri is notable for the presence of t2-hyperintense lesions in the left frontal lobe , the right mesial temporal lobe and the brainstem , which were minimally enhanced .\nan mr perfusion scan of the brain showed no significant increase in relative blood volume or relative blood flow in these lesions .\na ct of the thorax , abdomen and pelvis showed 5 small lung nodules ( maximum diameter 6 mm ) and a pneumatocele in the left lower lobe .\nas there was nothing further on history , exam or initial investigations to suggest cancer anywhere else , a pet / ct was not performed .\nimmunohistochemistry shows the lesion to be cd1a- and s100-positive , which is characteristic for histiocytosis .\ninitially , we were unsure of the cause of his right temporal lesion . given the rarity of lch with onset in the central nervous system ( cns ) in adults , the possibility of another tumor was raised , and so a second biopsy was performed .\nin retrospect , it would have been better to avoid performing this , as the diagnosis was already clear and his other lesions were attributable to lch .\nfurthermore , the procedure precipitated status epilepticus and led to preventable complications which ultimately contributed to his death .\nthis illustrates mild edema , hypercellularity and reactive changes , all of which are consistent with the edge of an inflammatory process .\nseptic shock ( likely due to ventilator - associated pneumonia ) and a pulmonary embolism complicated his course thereafter .\nhistiocytosis affecting his skull was thought to be in remission as a result of the treatment , as there was no sign of new or enlarging lytic lesions .\nafter discharge from the icu , he showed signs of critical illness myopathy / neuropathy .\nthere was widespread muscle atrophy and generalized weakness . he was unable to stand without support and his tracheostomy remained in place .\ngiven the suspicion of paraneoplastic brainstem inflammation , he was started on intravenous immune globulin ( ivig ) 400 mg / kg 5 days .\ntwo weeks after the initial treatment , the brainstem showed some improvement in the degree of flair hyperintensity ( fig .\nan mri 1 month after a second course of ivig showed these changes to be stable overall , with some increase in pontine enhancement ( fig .\nhe then developed recurrent pneumonia and septic shock , again requiring an icu admission . following this , his family elected a palliative approach to care and he died 6 months after his initial presentation .\nour patient 's episodes of hyperventilation followed by confusion are typical for seizures involving the right mesial temporal lobe ; the similarity to panic attacks has previously been identified in a case series .\nthe development of status epilepticus following biopsy of this region lends support to this being an epileptogenic focus . in\nhis cerebrospinal fluid ( csf ) , the finding of a high proportion of macrophages is striking .\nwe were unable to find literature specifically addressing the significance of this finding ; classically it is said to be associated with meningitis due to fungi or tuberculosis .\nnone of the other case reports we studied , including one with langerhans cells in the csf , reported this finding .\none series has shown elevations of neurofilament protein light chain , glial fibrillary acid protein and total tau protein in the csf of patients with lch affecting the brain .\nthese advise the use of cladribine for patients such as ours with multisystem and cns involvement ( cytarabine is thought be a reasonable alternative ) .\nmyelosuppression is the main dose - limiting toxicity ; this has best been studied in the setting of hairy cell leukemia where neutropenia was reported in 70% , anemia ( hb < 8 g / dl ) in 35% and thrombocytopenia in 10% of patients .\nthe most recent and thorough description of the neuropathology of lch comes from a series of 12 cases from grois et al . in 2005\nthe authors divide the pathology into 3 categories : ( 1 ) the typical circumscribed granulomas found in other organs ; ( 2 ) infiltrating granulomas with profound t - cell dominated inflammation and severe neurodegeneration ; ( 3 ) neurodegenerative lesions lacking langerhans cells , typically affecting the brainstem and cerebellum and resembling paraneoplastic encephalitis .\nit appears that the temporal and frontal lesions in our patient were of the second type ; it is probable that the biopsy came from the neurodegenerative part of the lesion rather than that containing langerhans cells .\nthe mri appearances of the brainstem in our patient are typical of the third type .\nthe presence of inflammation without langerhans cells has led to the view that these lesions are paraneoplastic in origin and that the neurodegeneration seen is thus autoimmune .\nthe langerhans cells are thought to take up normal neuronal antigens , provoking an immune response to these ; alternatively , the immune system may target antigens shared by langerhans cells and microglia . if an antigen is involved , the pathology reported by grois et al . \nthe antigens responsible for this phenomenon have not been identified and thus it was to be expected that our patient 's paraneoplastic panel was negative . using multiple immunosuppressants\nlangerhans cells in their normal form are thought to have a lifespan of months , and lch is characteristically a slowly progressive disorder .\nby contrast , cytotoxic t - cells typically have a half - life of 2448 h when activated .\nwhen used in the treatment of leukemia and lymphoma , it is typically given every 4 weeks .\nthus , the initial doses of cladribine would have been expected to lead to the death of a majority of neoplastic histiocytes while the t - cell - mediated inflammation would have been expected to resume within 34 weeks .\nivig would not have been expected to affect the viability of langerhans cells , but should have reduced t - cell activity for 34 weeks .\nit leads to a selective decrease in t - cells overall and an increase in regulatory t - cells . in children with lch\n, ivig has been reported to contribute to a stabilization of inflammation in 4/5 patients treated and to enable long - term remission in 1 case [ 11 , 12 ] .\nit has been suggested that ivig be given prophylactically to prevent the development of cns complications of lch , particularly diabetes insipidus , which tends to be irreversible .\nalternative agents reported to treat the paraneoplastic inflammation in lch include vincristine / cytarabine and all - trans - retinoic acid .\nthe use of steroids in our patient would not have been expected to have had long - lasting effects .\nbearing the above in mind , as well as the results of treatment in other t - cell - mediated paraneoplastic conditions , strong consideration should be given to agents that primarily target t - cells : steroids , ivig , plasma exchange and mycophenolate mofetil or cyclophosphamide .\nother paraneoplastic disorders recognized in patients with lch include cancer - associated retinopathy and spinocerebellar degeneration .\nbrain imaging should always be undertaken in an older patient with episodes suggestive of seizures , diabetes insipidus of central origin or symptoms suggestive of pituitary dysfunction .\nonce a diagnosis of lch is made , a brain biopsy is not essential if the mri appearances are typical for the inflammatory processes that accompany this condition .\nonce lch appears stable , prolonged treatment may be needed to prevent recurrence of inflammation .\nivig appears to be a reasonable adjunct to cladribine , particularly in a case such as this where cytopenias or infections limit the use of conventional chemotherapy .", "answer": "we report a case of langerhans cell histiocytosis in a 64-year - old male who presented with symptoms and signs of brain involvement , including seizures and hypopituitarism . \n the diagnosis was confirmed with a biopsy of a lytic skull lesion . \n the disease affecting the bone showed no sign of progression following a short course of cladribine . \n signs of temporal lobe involvement led to an additional biopsy , which showed signs of nonspecific neurodegeneration and which triggered status epilepticus . \n lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition . \n these lesions improved after treatment with cladribine . \n they remained stable while on treatment with intravenous immune globulin .", "id": 256} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSelective functionalization at N 2 -position of guanine in oligonucleotides via reductive amination\n\nPaper sections:\n\nMethods to synthesize modified oligonucleotides are of prime importance due to their role in a variety of applications. For example, modified oligonucleotides are useful to understand the effect of specific chemical modifications on nucleic acid stability, ability of DNA to replicate, and to study nucleic acid-protein interactions. [1][2][3][4] In addition, modified oligonucleotides also have diagnostic or therapeutic applications; for example in nucleic acid sequencing and identification, or in small interfering RNA technology for enhanced stability and target affinity in vivo. 5 However, selectively modified oligonucleotides are difficult to obtain, and are most commonly synthesized on a solid-phase using the corresponding phosphoramidite derivative. The synthesis of the desired phosphoramidite, in turn, involves several steps including nucleotide protection and deprotection, and purification processes such as ion exchange and HPLC. This makes the overall process challenging, time-consuming, and expensive.
One approach to circumvent this problem is to introduce the desired modifications after DNA (or RNA) synthesis. However, this would require methods that can chemoselectively target one out of the four nucleobases. Although a number of reagents are known to form adducts with DNA 6,7
, very few chemical methods exist for selective targeting of one nucleobase over others. One such example was reported by Okamato et al., in which they showed that 5-methylcytosine, an important epigenetic modification, can be sequence selectively oxidized using osmium based reagents for the selective cleavage of a DNA strand. 8 In another example, Geigle et al. have performed selective modification at the O 6 position of guanine in DNA using metal carbenes.
9
The selective modification of guanine in DNA is biologically relevant. In particular, modifications at the N 2 -position of guanine frequently lead to mutagenic DNA adducts, and the availability of such substrates is essential to elucidate the biological ramifications of adduct formation. Recently, N 2 -modified deoxyguanine oligonucleotides were used as substrates to study the activity of the enzyme Top1, which is highly susceptible to modifications in the DNA bases. 10 Guanine nucleotide and its derivatives are also interesting as they self-assemble to form higher order structures in the presence of some metal ions. These have a variety of applications as anticancer hydrogels 11 , inducers of effective cell growth 12 , and selective absorption of anionic dyes from water 13 . These properties can be tuned by appropriate chemical modifications. Moreover, substituted guanine containing deoxy-oligonucleotides have been shown to efficiently fold into G-quadruplexes, biologically relevant structures comprised of four G-rich DNA strands. The modified G-quadruplexes have several desirable characteristics like enhanced thermal stability, 14 and anti-thrombin and anti-HIV properties. 15,16 Antisense oligonucleotides containing guanine, substituted at its N 2 -position with cationic groups, show enhanced DNA (and RNA) binding, while preserving RNase H activity required for gene silencing. 17,18 In summary, the utility of N Despite its importance, very few reagents are available for the post-synthetic functionalization of the exocyclic amine of guanine nucleotide selectively over other nucleotides. Although previous studies have reported reductive alkylation of the exocyclic amine of guanine derivatives, 19,20,21 a systematic study of the reactivity and selectivity of the exocyclic amine of guanine in a complex chemical environment such as DNA is lacking. The availability of chemical methods for guanine N 2 modification are particularly important as the N 2 -alkyl deoxyguanine nucleotides are not substrates for DNA polymerases (except for polymerase \u03ba 22), precluding the use of enzymatic methods for modified nucleotide incorporation into DNA. Here, we have systematically studied reductive amination of guanine with various aliphatic aldehydes to selectively make guanine N 2 substituted DNA oligonucleotides. We show that this simple yet powerful reaction can selectively modify the N 2 -position of guanine, leaving the other aromatic exocyclic amine bases (viz. cytosine and adenine) unaffected under the reaction conditions.
We first treated an aqueous solution of each of the four nucleotide monophosphates (NMPs) individually with propanal in the presence of sodium cyanoborohydride (Table 1). Near quantitative conversion was obtained for guanine (both dGMP and GMP) to give the monoalkylated product after six hours. The product identity and site of the reaction was confirmed by NMR methods. The product assignment was further supported by the observation that inosine triphosphate (ITP), lacking the N 2 amine, did not react under these conditions. Under the same reaction conditions, no conversion was observed for adenine and cytosine nucleotides, both of which contain an exocyclic amine, even after 24 hours, indicating that the reaction was selective for guanine (Table 1). Similarly, uracil and thymine derivatives did not react under these conditions. We also treated a mixture of all the four deoxy NMPs (dNMPs) under the given reaction conditions. After 6 hours, the crude reaction mixture was analysed by HPLC, which indicated that even in the mixture, only dGMP successfully reacted with propanal to form N 2 -propyl substituted dGMP, while others remained unchanged (Fig 1). Not surprisingly, screening several aliphatic aldehydes in this reaction revealed that the reaction became more sluggish as the hydrophobicity of the aldehyde increased. This was likely due to the reduced solubility of the aldehyde in aque-ous medium, and correlated well with the calculated logP values for the aldehydes. In agreement with this, we also found no reaction with aromatic aldehydes under the same reaction conditions.
Although the exact reason for selectivity towards guanine needs to be investigated, it is likely that the N 2 -amine of guanine is significantly more nucleophilic, as it is part of a guanidinium system. In comparison, the amidines of cytosine and adenine are less nucleophilic. 23,24 We further note that aliphatic ketones showed negligible reactivity with guanosine under the given reaction conditions, indicating that in addition to the reactivity of guanine, electronic and steric properties of the carbonyl substrate also play an important role in differentiating the exocyclic amine of guanine. The selectivity observed for guanine was remarkable because of the ability of a simple reaction to distinguish between GMP/dGMP and other nucleotide bases, indicating that this reaction could potentially be applied to post synthetic modification of oligonucleotides, allowing guanine base to be selectively targated. To test this idea, we started with a four nucleobase DNA sequence containing all four nucleotides, i.e., d(GTCA). When this oligonucleotide was treated with propanal and NaCNBH 3 , a new peak appeared in HPLC, but complete consumption of the starting material was not observed. So, we performed systematic optimization of the reaction conditions, including temperature and reagent concentrations. We found that although an increase in temperature up to 45\u00b0C increased yield to 70%, any further increase led to significantly lower yields likely due to decomposition of the reducing agent. In contrast, increasing aldehyde concentration pushed the reaction towards completion, with almost complete disappearance of starting material within 3 hours, and appearance of a new peak in the HPLC profile (See Fig. 2, and Table 2). A mass spectrometric analysis of this peak showed a single propyl modification in the oligonucleotide, and was consistent with a modification on guanine. We note that even at 1500-fold excess of aldehyde, other nucleobases remained unreacted. DNA concentration was 5 mM in water, a % conversion was calculated based on area under the peak with respect to starting material; b reaction was stopped after 8 hours since there was no significant change in % conversion after 3 hours.
We then tested a series of DNA oligonucleotides using the above reaction protocol, and found that method works efficiently with all tested DNA sequences irrespective of the position of guanine, and the number of cytosine and adenosine bases (Table 3). In all G-containing oligonucleotides, a new peak appeared in the RP-HPLC profile indicating likely formation of one new product in the reaction mixture. This new peak was attributed to reaction at the single guanine site, as oligonucleotides lacking guanine did not show any change in HPLC profile after six hours (Table 3, Entry ODN5, ODN7, ODN10). To further confirm this result, ODN11 was treated with phoshodiesterase I from Crotalus adamanteus venom followed by calf intestine phosphodiesterase (CIP) digestion. This treatment hydrolyzes the DNA into individual nucleosides and allows product identification by HPLC. Analysis of the hydrolyzed products showed the presence of N 2 -propyl deoxyguanosine nucleoside, along with other unreacted deoxynucleosides (dC, dT and dA). Taken together, the data presented above strongly support that the reaction takes place regio-and chemo-selectively at the N 2 -position of guanine in DNA, leaving all other nucleobases unaffected. We applied this reductive amination strategy to functionalize a G-quadruplex forming sequence TT(GGGT) 4 . A mass spectrometric analysis of the modified sequence showed that eleven out of the twelve guanine bases were modified, indicating the potential of this reaction to densely functionalize DNA. When oligonucleotide ODN11 was treated with more hydrophobic aliphatic aldehydes, the reaction was sluggish, and the % conversion was significantly reduced for aldehydes having logP more than 1.5 (Table 4). We further explored the potential of this reaction to introduce bioorthogonal handles such as azide or alkyne into a DNA oligonucleotide (Table 4). Aldehydes with suitable bioorthogonal handles reacted with ODN11 to give moderate to good yields of the monosubstituted product. The bioorthogonal functionality introduced on oligonucleotides in this manner can be further reacted with a desired probe for example a fluorophore or affinity tag to obtain labeled oligonucleotides. We have demonstrated this using dibenzylcyclooctyne-PEG 4 -5/6-tetramethylrhodamine (DBCO-TAMRA) as a representative example to illustrate the scope of the reaction. We first reacted ODN11 with 5-azido-1-pentanal, and the product was washed with ethyl acetate to remove organic reagents. The bioorthogonal handle containing DNA was further reacted with DBCO-TAMRA under strain mediated copper free click conditions. The formation of the fluorescently labeled DNA was confirmed by HPLC, as well as HRMS (Fig. 3). Oligonucleotide used is d(AACTGACTCA). DNA concentration was 5 mM in water; aldehyde = 1500 equiv. and NaCNBH3 = 150 equiv. w.r.t DNA; conversions are based on area under the peak (\u03bb = 253nm). In summary, we have shown that reductive amination with DNA bases can selectively modify guanine in nucleic acids. This simple yet powerful method can readily produce oligonucleotides modified at the N 2 -position of guanine. We have also shown an application of this method to access fluorescent DNA labeled specifically at guanine base. The method is simple and readily accessible even for biologists, and significantly reduces the time and cost involved in using modified phosphoramidites for selective labeling of guanine in nucleic acids.
", "answer": "Chemo-and site-specific modifications in oligonucleotides have wide applicability as mechanistic probes in chemical biology. Here we have employed a classical reaction in organic chemistry, reductive amination, to selectively functionalize the N 2 -amine of guanine/2'-deoxyguanine monophosphate. This method specifically modifies guanine in several tested DNA oligonucleotides, while leaving the other bases unaffected. Using this approach, we have successfully incorporated desired handles chemoselectively into DNA oligomers.", "id": 257} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbartter syndrome ( bs ) is a rare inherited renal tubular disorder characterized by renal salt wasting , hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism1 , 2 ) . although bs is a typical tubular disorder ,\nthere have been several case reports of patients who developed focal segmental glomerulosclerosis ( fsgs ) , a glomerular lesion , during the course of bs3 - 7 ) .\nsuch cases support a possible link between the two diseases , and indicate that stimulation of the renin - angiotensin system ( ras ) and increased angiotensin ii in response to chronic glomerular hyperfiltration due to salt - losing tubulopathy may lead to secondary fsgs3 , 4 , 8) .\nin addition to fsgs , several other factors have been reported to influence the renal survival of patients with bs , including recurrent episodes of dehydration during early infancy , chronic hypokalemia , long - term use of non - steroidal anti - inf lammatory drugs , nephrocalcinosis , and mutations in the bsnd gene9 - 11 ) .\nhowever , there have been only a few case reports of patients with bs who underwent renal transplantation6 , 12 - 15 ) . here ,\nwe present a case of a patient with bs who developed fsgs and subsequently underwent renal transplantation due to aggravation of his renal function .\nwe also review previously reported cases of both diseases and cases of individuals with bs who underwent renal transplantation .\nthere were no perinatal problems including polyhydramnios , and the family history was unremarkable . at age\n3 months , the patient visited a hospital due to recurrent febrile episodes and poor weight gain . the patient was diagnosed as bs , and potassium supplement and indomethacin medication were started . however ,\nhis compliance to the drug was very poor . detailed clinical and laboratory data from that time are unavailable . at age 7 , proteinuria was incidentally detected upon routine follow - up urinalysis .\na renal ultrasonography revealed diffusely increased parenchymal echogenicity without definite evidence of nephrocalcinosis or nephrolithiasis . at age 8 ,\na renal biopsy was conducted at the hospital due to persistent proteinuria ( 24-hour urine protein excretion 3,840 mg / day , serum albumin 3.4 g / dl , and serum creatinine 1.2 mg / dl ) .\nhis proteinuria did not respond to 4 weeks of oral prednisolone ( 2 mg / kg / day ) treatment . at age 10 ,\nthe patient 's height was 123 cm ( < 3rd percentile ) , weight was 36 kg ( 90 - 97th percentile ) , and blood pressure was 117/69 mmhg at the time of admission .\nthe laboratory examination revealed a serum creatinine level of 3.1 mg / dl , a sodium level of 138 mmol / l , a potassium level of 3.7 mmol / l , a chloride level of 103\nmmol / l , a bicarbonate level of 30 meq / l , a magnesium level of 2.0\n/ ml / hr ( normal range 1 - 2.5 ) , an aldosterone level of 558 pg / ml ( normal range 50 - 194 ) , and a spot urine calcium ( mg ) to creatinine ( mg ) ratio of 0.02 . additionally , the patient 's bone age was 6 years 5 months upon admission .\ngenetic analysis revealed a homozygous p.trp(tgg)610stop(tga ) mutation in exon 16 on the clcnkb gene .\nhis renal function deteriorated progressively for one year thereafter , at which point hemodialysis was started .\nsubsequently , the patient underwent renal transplantation successfully from a deceased donor at age 16 .\nthe post - transplantation course has been uneventful for more than 3 years , with complete disappearance of bs without recurrence of fsgs .\nclinically , bs can be classified into two variants , antenatal / neonatal bs and classic bs according to the onset age .\ngenetically , bs can be classified into at least 5 subtypes according to underlying mutant genes , all of which are expressed in the tubular epithelial cells of the thick ascending limb of the loop of henle .\nbs type i is caused by loss - of - function mutations of slc12a1 encoding the apical sodium - potassium - chloride cotransporter ( nkcc2 ) , while bs type ii is caused by loss - of - function mutations of kcnj1 encoding the apical inwardly - rectifying potassium channel ( romk ) , bs type iii is caused by loss - of - function mutations of clcnkb encoding the basolateral chloride channel ( clc - kb ) , bs type iv is caused by loss - of - function mutations of bsnd encoding barttin , and bs type v is caused by gain - of - function mutations of casr encoding the basolateral calcium sensing receptor ( casr)2 ) .\nbs is an inherited tubular disorder ; however , our patient developed fsgs , an acquired glomerular lesion , later in the disease course .\nthere have been five similar case reports of bs complicated by fsgs3 - 7 ) ( table 1 ) .\nin addition , there is an additional report of a patient with classic bs who developed end - stage renal disease due to glomerulopathy12 ) .\nhowever , this patient was excluded from the review because the renal pathology was described as ' diffuse ' glomerulosclerosis . as shown in table 1 ,\npatients with bs and fsgs show development of fsgs independently of gender , clinical variants of bs or genetic subtypes of bs .\none patient had nephrocalcinosis , and three patients had a history of long - term non - steroidal anti - inflammatory drug treatment prior to the onset of proteinuria .\nthree patients had progressed to chronic renal failure , but the rate of progression was variable .\none other patient revealed mildly decreased renal function one year after diagnosis with fsgs5 ) .\nnormal renal function was maintained in the remaining two patients , and , interestingly , proteinuria resolved completely in one of these patients after one year treatment with potassium supplements , spironolactone , and indomethacin3 ) .\nthe renal pathologic findings were described in detail in three cases , two of which had perihilar type fsgs .\nthe perihilar variant is common in patients with secondary forms of fsgs mediated by glomerular hyperfiltration or other adaptation after loss of renal mass8 , 16 ) .\nthese findings suggest that fsgs complicated by bs may be a secondary lesion due to adaptive response to chronic hyperfiltration by chronic salt - loss and resultant chronic stimulation of the renin - angiotensin system .\nseveral case reports of gitelman syndrome complicated by fsgs support this explanation17 , 18 ) .\ncase reports of patients with bs who underwent renal transplantation are also rare , and the causes of esrd include progression of fsgs or other causes including complication of long - term non - steroidal anti - inflammatory drug treatment6 , 12 - 15 ) . in one of the patients , pre - emptive bilateral native nephrectomies and renal transplantation were conducted prior to the onset of esrd due to severe , clinically brittle , neonatal bs15 ) . in all of the cases ,\ntransplantation was successful and bs disappeared completely after transplantation as shown in our patient . in summary , bs may be complicated by fsgs due to adaptive response to chronic salt - losing nephropathy , and fsgs may cause esrd in some patients .", "answer": "bartter syndrome ( bs ) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting , hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism . \n there have been several case reports of bs complicated by focal segmental glomerulosclerosis ( fsgs ) . here \n , we have reported the case of a bs patient who developed fsgs and subsequent end - stage renal disease ( esrd ) and provided a brief literature review . \n the patient presented with classic bs at 3 months of age and developed proteinuria at 7 years . \n renal biopsy performed at 11 years of age revealed a fsgs perihilar variant . \n hemodialysis was initiated at 11 years of age , and kidney transplantation was performed at 16 years of age . \n the post - transplantation course has been uneventful for more than 3 years with complete disappearance of bs without the recurrence of fsgs . \n genetic study revealed a homozygous p.trp(tgg)610stop(tga ) mutation in the clcnkb gene . in summary , \n bs may be complicated by secondary fsgs due to the adaptive response to chronic salt - losing nephropathy , and fsgs may progress to esrd in some patients . \n renal transplantation in patients with bs and esrd results in complete remission of bs .", "id": 258} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nreliable information on morbidity and mortality is the key for evidence - based public health practice .\nmore emphasis on estimating burden of diseases was given at global level , especially since the launch of global burden of disease study .\n while the decision - making priorities of global health authorities are dependent on these projected data , developing countries often lack the local data for proper public health planning .\nhealth professionals still fights to establish vital registration , while the morbidity surveillance is still in its initial stage . in countries where information is available ,\ndata from ambulatory care services , primary healthcare centers , and outpatient departments ( opd ) are often lacking .\neconomic impacts of the mild to moderate ill health conditions are considerable given the large number of patients utilizing these services .\nas an example , in sri lanka , more than 43 million visits are made to the opds in government hospitals annually .\ngiven that the only 50% of outpatient care is delivered through public sector , the total outpatient visits are estimated to be more than 80 million , four times the sri lanka population of 20 million . despite this heavy burden , information on opd morbidities are not routinely collected and used in healthcare planning .\nas a preliminary study to assess the burden of disease and morbidity pattern in opd , we conducted a rapid survey in a tertiary care hospital in sri lanka .\nstudy sample consisted of opd patients visiting teaching hospital peradeniya , which is the teaching hospital for second largest medical school in sri lanka .\nthree of the six authors physical presented at the opd during the study period , explained the procedure to patients , and consented patients filled a self - administered short questionnaire .\na half - page questionnaire was used and the main problem which patients sort medical advice was inquired .\na total of 3817 patients attended opd during the study period and 1908 were recruited as the study sample using the systematic sampling strategy .\nof them , 1439 completed the questionnaire with a response rate of 75.4% . a significantly higher number of females ( 924,64.2% ) visited the opd compared to males ( 515,35.8% ) ( chi square for goodness of fit 116 , p<0.001 ) .\nthe age of the patients attending the opd ranged from 1 year to 89 years .\nthe mean age of the study sample was 40 years ( sd = 19 years ) .\nmajority of the females attending the opd were of middle age while males were distributed evenly among all age categories .\nthe mean age of females was significantly higher than that of males ( t = 4.03 , p<0.001 ) .\nhousewives constituted the major occupational group among females , accounting for 52% of the total sample , followed by adolescents ( 15.9% ) .\nten leading cause of opd visits were nonspecific body aches and pains 225 ( 15.6% ) ; respiratory symptoms ( cough and cold ) 151 ( 10.5% ) ; abdominal pain 122 ( 8.5% ) ; fever - 117 ( 8.1 ) ; backache and joint pains 112 ( 7.8 ) ; skin conditions - 106 ( 7.4 ) ; constipation - 84 ( 5.8 ) ; chest pain 66 ( 4.6 ) ; diarrhea - 59 ( 4.1 ) ; and dog bite / s 51 ( 3.5 ) . table 1 shows the leading morbidities according to sociodemographic profile of the patients . among children ( 10 years)/school children , cough and cold was the commonest complaint followed by dog bites .\nconstipation ( 14.5% ) was the commonest presenting complaint among tamils ( 6.3% ) but was not in the leading five commonest complaints among the other ethnic groups .\nmain presenting symptom among adolescents was various skin conditions , which was third commonest condition among young adults .\ncommonest presenting complaint by demographic characteristics among patients attending outpatient department of teaching hospital peradeniya , sri lanka ( n = 1 439 )\nthis could be explained partly from the so - called male - female health survival paradox \n( i.e. , males report better health than females , but encounter higher mortality at all ages ) .\nthere is growing evidence to conclude that men are healthier , but have substantially higher mortality rates .\nhowever , this could be also due to a gender difference in health - seeking behavior as shown in previous studies.[46 ] children less than 10 years accounted for only 5% of the opd patients , which shows a marked difference from the private sector utilization in sri lanka where 32% of encounters were reported as children , which was completely different from the findings of the present study .\npreviously , respiratory tract problems were reported as the commonest encounter in government phc setting as well as in gp practice in sri lanka , with higher percentages ranging from 20% to 55%.[79 ] in our study , respiratory problems was the commonest among younger age groups . however , nonspecific body aches and pains was the leading encounter .\nhowever , this problem needs to be studied to provide meaningful services . despite having low annual numbers of rabies\n, dog bite showed to be a leading problem among children . reported constipation encounters as leading reason for opd care seeking among tamil ethnic group\nthese observations from a single hospital could not be generalized to sri lanka or other developing countries .\nhowever , our study provides early evidence for probability of changing morbidity patterns with demographic transitions that should be taken into account in public health program planning .", "answer": "background : global disease burden estimates often lack real data on morbidities , especially from patients treated in outpatient department ( opd ) . in sri lanka , around 40 million visits are made annually to the opds in government hospitals and we conducted a preliminary study to assess the morbidity profile of these opd patients.methods:patients attending the opd , in teaching hospital peradeniya , sri lanka , was recruited into the study using systematic random sampling procedure . \n a self - administered , structured questionnaire was used to collect data . \n investigators explained the study to patients and data collection was completed before seeing the physician . \n self - reported presenting complain was used to analyze the morbidity profile of the patients.results:the study sample consisted of 1 439 patients ( male - 515 , female - 924 ) . \n the mean age of the study sample was 40 years ( sd = 19 years ) . \n the mean age of the females were statistically significantly higher than that of the males ( t = 4.03 , p<0.001 ) . \n housewives constituted the major occupational group ( 52% ) followed by students ( 15.9% ) . \n the most common presenting complains reported were body aches and pains ( 15.6% ) , cough and cold ( 10.5% ) , and abdominal pain ( 8.5% ) . \n leading cause of hospital visit among different demographic categories showed statistically significant variations.conclusions:the morbidity pattern observed in this patient population was not previously reported . \n opd surveillance should be established to understand the changing pattern of minor ailments which might have a huge impact on health of the public .", "id": 259} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\novotesticular disorder of sex development ( ot - dsd ) is a rare disorder of sexual \n differentiation characterized by the presence of testicular tissue with distinct \n seminiferous tubules and ovarian tissue with mature ovarian follicles in the same gonad \n ( ovotestis ) or separately in a single individual ( 1 , \n 2 ) . ot - dsd\nit constitutes between 3 and 10% of the \n total dsd and presents significant diagnostic and management challenges ( 3 , 4 ) .\ntypically , \n both mullerian and wolffian duct derivatives are seen , and most affected individuals \n commonly present with ambiguous external genitalia as neonates or infants .\nhowever , the \n phenotype of the external genitalia may range from normal male to normal female depending on \n the degree of testicular tissue present .\nthe ovotestis is usually the most common gonad in \n individuals with ot - dsd , and such gonads are known to be at an increased risk of developing \n germ cell tumors ( 5 ) .\nmore than five hundred cases of ot - dsd including familial cases have been reported in \n medical literature ( 3 , 6 , 7 ) .\nepidemiologically , the geographical \n distribution of ot - dsd shows a higher prevalence in the african continent , especially among \n south african blacks , with the number of published cases being 17 per 100 million people , \n followed by europe at 15.3 .\nage and mode of presentation is often variable and \n usually comprises hypospadias , unilateral or bilateral cryptorchidism , inguinal hernia , \n urogenital sinus , gynecomastia at pubertal age or lower abdominal mass in adulthood ( 4 ) .\ninternally , the presence of an ovotestis is the most \n common finding followed by ovaries ( 4 , 9 ) .\nthe chromosomal findings in ot - dsd were first reported in 1959 by hungerford , who \n demonstrated a 46,xx chromosomal complement in peripheral blood lymphocytes of an individual \n with this disorder ( 10 ) . ot - dsd is a genetically \n heterogeneous condition with the predominant karyotype being 46,xx , while 46,xx/46,xy \n chimerism , 46,xy karyotype and x - y translocation are less frequent ( 4 ) .\nthe objective of this paper is to describe the diverse clinical , \n cytogenetic and histopathological features of five patients diagnosed with ot - dsd in sri \n lanka .\nthis is a report of the clinical , cytogenetic and histopathological data of patients with \n ot - dsd who were referred to the human genetics unit for cytogenetic evaluation between 2005 \n and 2011 .\nthis facility serves as the main referral center for cytogenetic testing in sri \n lanka , and the majority of children with dsd in the country undergo karyotype testing at \n this center .\nthe diagnosis of ot - dsd had been \n confirmed by histopathological examination of the gonads , which were biopsied either \n laparoscopically or at exploratory laparotomy .\nfive milliliters of peripheral blood was \n obtained from each patient , and chromosomal analysis was performed on routinely cultured \n lymphocytes after gtg - banding .\nkaryotyping was done according to guidelines of the \n international system for human cytogenetic nomenclature ( iscn , 2005 ) .\nat least 30 \n well - spread and well - banded metaphases were examined in each patient by an experienced \n cytogeneticist .\nthe age , sex of \n rearing , mode of presentation , status of the external and internal genitalia and karyotypes \n of the patients are summarized in table \n 1 .\ntheir ages ranged from 2 mo to 47 yr , and all were reared as males . in four \n of the patients ( cases 1 , 3 , 4 and 5 ) ,\ntwo \n patients ( cases 1 and 3 ) had perineal hypospadias with bilateral cryptorchidism , while the \n other two patients ( cases 4 and 5 ) , who were siblings , both had male external genitalia with \n a short , blind - ending vagina and bilateral inguinal lumps .\ncase 2 was reared as a male but \n started feminizing and developed female secondary sexual characteristics at puberty with \n gradual atrophy of both testes .\ncase 1 underwent surgical correction for perineal \n hypospadias during early childhood but remained undiagnosed until an exploratory laparotomy \n performed for an intra - abdominal lump led to the diagnosis of ot - dsd at the age of 47 yr . in \n addition to the lower abdominal mass , this patient was observed to have gynecomastia . \n\ntwo patients had \n bilateral ovotestis : one had an ovotestis on one side and an ovary on the other side , the \n other had an ovotestis on one side and a testis on the other side ; the remaining patient had \n an ovary and testis separately on either side .\nfour patients ( cases 1 , 2 , 4 and 5 ) had a \n 46,xy chromosome complement , while 46,xx/46,xy chimerism was observed in the remaining \n patient ( case 3 ) . there were no cases of 46,xx karyotype . \n\ntable 1 profiles of the five patients with ovotesticular disorder of sex \n developmentcaseagesex of rearingindication for investigationexternal genitaliainternal genitalia / gonadskaryotype147 yrmaleambiguous genitalia at birth / abdominal \n mass in adulthoodperineal hypospadias , bilateral \n cryptorchidismuterus with tubes , left ovotestis and \n right testis 46,xy223 yrmalefemale secondary sexual characteristics at \n puberty with gynecomastiamale external genitalia with bilateral \n atrophic testes uterus with tubes and bilateral streaky \n ovaries and atrophic testes46,xy32 momaleambiguous genitalia / inguinal lumpperineal hypospadias , bilateral \n cryptorchidismuterus with tubes , left ovary and right \n ovotestis46,xx/ 46,xy49 momaleambiguous genitalia / bilateral inguinal \n lumpsmale external genitalia with blind - ending \n vaginauterus with tubes and bilateral \n ovotestis46,xy55 yrmaleambiguous genitalia / bilateral inguinal \n lumps male external genitalia with blind - ending \n vaginauterus with tubes and bilateral \n ovotestis46,xy \n\not - dsd is a rare disorder of sexual differentiation that is phenotypically and genetically \n heterogeneous with wide - ranging manifestations .\nthe presence of well - differentiated ovarian \n and testicular tissue in the same individual , whether as a single tissue - type gonad or an \n ovotestis , is the hallmark of this condition ( 9 ) .\nmost \n patients with ot - dsd have ambiguous genitalia and are often diagnosed within the first few \n months to years of life ( 1 , 4 , 9 ) .\nin addition to ambiguous \n genitalia , patients may present with inguinal hernias , gynecomastia during adolescence or \n lower abdominal mass in adulthood ( 4 , 11 ) .\nfour out of 5 patients in this series had ambiguous genitalia \n diagnosed in the first few months to years of life , and all were reared as phenotypic males . \n\ninguinal hernias and gynecomastia were also present in some patients . a small number of \n ot - dsd cases are incidentally picked up during laparotomy for unrelated causes .\none of the \n patients in this series had a similar presentation ; he presented with a lower abdominal mass \n in the fourth decade that was later discovered to be an 18-wk - size uterus at laparotomy . a \n similar case of ot - dsd in a 42 yr old was reported in north india ( 4 ) . in ot - dsd\n, the degree of virilization of the external genitalia \n depends on the capacity of the testicular tissue to secrete testosterone .\nprevious studies \n indicate that although approximately 70% of ot - dsd patients are raised as males , less than \n 10% have normal male external genitalia ( 1 ) .\nit is \n generally believed that the leydig cell function of the dysgenetic testis is inadequate for \n normal virilization ( 4 ) , and this is exemplified in \n this series by case 2 , who had bilateral atrophic testes and started feminizing at puberty . \n\nprevious reports have also indicated that testicular tissue in ot - dsd patients becomes \n dysgenetic and that germ cells begin to disappear with increasing age ( 12 ) .\nthe patients in this study had internal genital organs ranging from streaky ovaries and a \n uterus to atrophic testes , but the common presenting gonad was the ovotestis .\nit is known \n that gonadal tissue may be located at any level along the route of embryonic testicular \n descent and is frequently associated with an inguinal hernia\n. a sub - classification of ot - dsd \n based on the type and location of the gonads has been described ( 13 ) . according to this classification , ot - dsd\nis considered to be lateral \n if a testis is present on one side and an ovary is present on the other side ( case 2 ) , \n unilateral if an ovotestis is present on one side and a testis or ovary is present on the \n other side ( cases 1 and 3 ) and bilateral if an ovotestis is present on both sides ( cases 4 \n and 5 ) .\n( 9 ) reported \n that the ovotestis was the most frequent gonad , accounting for 59% in their series of 16 \n patients with ot - dsd , and krob et al .\n( 3 ) also reported that an ovotestis was found in 44.4% of 568 gonads examined . the \n same observation is reflected in this series , in which 4 out of 5 cases ( 1 , 3 , 4 and 5 ) had an \n ovotestis and 2 of the patients , who were siblings , had bilateral ot - dsd . with regard to the \n frequency of gonadal distribution\n, it is reported that the most common form is ovotestis \n plus ovary followed by bilateral ovotestis and ovary on one side and testis on the other \n side , representing 34% , 29% and 25% of cases , respectively ( 8) .\nprevious studies have reported that the risk of germ cell tumors , especially \n dysgerminomas , in patients with ot - dsd ranges from 4% among those with the 46,xx karyotype \n to up to 10% in those with 46,xy and 46,xx / xy chimerism ( 4 , 5 ) .\nanalysis of the chromosomal distribution of ot - dsd shows that about 5065% cases have a \n 46,xx chromosomal constitution followed by 46,xx/46,xy chimerism , while less than 10% have a \n 46,xy karyotype ( 1 , 8 , 9 ) .\nthe 46,xy karyotype is believed to be \n extremely rare and equally distributed throughout asia , europe and north america ( 3 ) .\nin contrast to published reports ( 3 , 4 , 8 , 9 , 14 ) , the predominant karyotype was 46,xy in 80% of the \n patients in this series . there is no apparent reason for 46,xy being the most common \n karyotype in this study other than the small number of patients studied , with possible \n over - representation of the 46,xy karyotype in this study sample , or it could be reflective \n of the pattern seen in the sri lankan population .\nkaryotypes such as 46,xx/46,xy , which was \n seen in only one patient , are thought to result from chimerism , possibly from double \n fertilization ( involving two spermatocytes one x and one y ) of either a binucleate ovum or \n of an ovum and its polar body ( 15 ) . in some of the patients , proper investigation and accurate\ndiagnosis had been delayed for \n many decades in spite of ambiguous genitalia being detected early in life , which led to \n clinical and psychological problems in their adult life .\nit is therefore recommended that in \n addition to cytogenetic evaluation , phenotypic males with ambiguous genitalia should be \n thoroughly investigated by means of either abdominal ultrasound scan and/or exploratory \n laparoscopy / laparotomy with histopathological examination to properly assess the exact \n nature of their internal genital system .\nalthough considered a rare presentation , the cases \n reported in this series suggest that abnormal inguinoscrotal or abdominal masses may occur \n in ot - dsd and should be considered in the differential diagnosis of patients , especially in \n those with cryptorchidism and inguinal hernia having the 46,xy karyotype .", "answer": "ovotesticular disorder of sex development ( ot - dsd ) is a rare disorder of sexual \n differentiation in which the gonads of an individual are characterized by the presence of \n both mature ovarian and testicular tissues . \n the objective of this paper is to report the \n clinical , cytogenetic and histopathological findings in sri lankan patients diagnosed with \n ot - dsd who were referred to the human genetics unit for cytogenetic evaluation during 2005 \n to 2011 . \n five patients had histopathologically confirmed ot - dsd . \n their ages at \n presentation ranged from 2 mo to 47 yr . \n clinical symptoms varied from ambiguous genitalia \n and inguinal hernias at birth to a lower abdominal mass presenting in adulthood . \n all 5 \n were reared as phenotypic males . \n an ovotestis was detected in all cases except one , and \n the predominant karyotype was 46,xy . \n the findings in this series of predominantly 46,xy \n karyotype are in contrast to previously published reports that have reported 46,xx as \n being the predominant karyotype . \n it is therefore recommended that individuals with \n ambiguous genitalia who have the 46,xy karyotype should be thoroughly investigated by \n ultrasonographic or laparoscopic assessment to determine the exact nature of their \n internal genital organs . ot - dsd \n should also be considered in the differential diagnosis of \n patients with cryptorchidism and inguinal hernia .", "id": 260} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 21-month - old male patient , 75 cm in height and 10 kg in weight , experienced tricuspid valve regurgitation ( tvr ) and was scheduled to undergo tricuspid valve plasty . the tvr was discovered in a follow - up test 1 year after he had undergone ventricular septal defect repair surgery . before tricuspid valve plasty\n, a tee was performed , which showed a level 3 - 4 tvr and severe right ventricular hypertrophy .\natropine , thiopental sodium , and vecuronium were administered to induce anesthesia and muscle relaxation .\na catheter was placed at the left radial artery to measure the constant blood pressure and analyze the abga ( table 1 ) .\nthere were complications due to the adhesion of the svc and ivc near the surgical site .\ntherefore , a 20 fr and 22 fr cannula was placed on them , respectively . 2 u of packed red blood cells ( prc ) , albumin , and mannitol was used as the priming solution . immediately after activating the cardiopulmonary bypass , the measured hematocrit level was 27.5% .\nthe acid - base balance management mid - surgery was performed with an -stat . during extracorporeal circulation ,\nthe body temperature was aimed at a moderately low degree of 25. the perfusion rate was kept at 0.5 - 1.0 l / min .\nafter tricuspid valve surgery , the patient was weaned from the cardiopulmonary bypass by reducing the perfusion rate of the machine and starting mechanical ventilation .\nthe total anesthesia , surgery and extracorporeal circulation time was 510 minutes , 420 minutes and 180 minutes , respectively .\nthe amount of blood loss was estimated to be 800 ml . during surgery , 600 ml of a crystalloid solution , 3 u prc and 2 u platelets were administered .\nhowever the patient 's eyes could not focus , and his upper and lower limbs experienced intermittent convulsions .\nbrain computed tomography revealed findings indicative of a cerebral infarction in the occipital lobe ( fig .\neeg was performed , which showed no abnormal findings of alpha rhythm loss , which is customary in cortical blindness .\nphenobarbital was administered until 19 days after surgery under the suspicion of a connection between the ocular deviation and the convulsions .\nthe convulsions did not return , but the reaction to light or objects in front of the eyes did not trigger an avoidance response from the patient .\nthere were no hopeful clinical signs of a visual recovery but fundoscopy showed normal findings .\non the postoperative day 28 , when the flash visual evoked potential ( fvep ) and mri had been planned , the patient 's eyes refocused .\nhe was able to recognize the objects in front of his eyes , could walk and avoid things in his path , and was able to recognize his guardians .\npost surgery visual loss or reduction can be caused by a variety of factors , and occurs 0.1% to 1% of cases .\nvisual loss is caused by damage to any connecting striate area between the cornea and occipital cortex .\ndirect pressure on the eyeball , indirect increase in ocular tension due to improper positioning and blood vessel damage can cause central retinal artery occlusion or ischemic optic nerve damage , which can lead to visual loss . in addition , a severe decrease in blood pressure , emboli , and thrombus mid- or post - surgery can cause an infarction in the occipital cortex , which can lead to cortical blindness .\nvisual loss after a cpb might be caused primarily due to emboli , severe low blood pressure , acute anemia , hypoxia or a combination of these factors . in the present case\ntwenty seven cases were cortical blindness , of which 22 cases occurred after cardiac surgery ( 81% ) .\naldrich et al . reported a retrospective study of 25 patients , where the causes of cortical blindness were natural ischemic stroke in 8 patients ( 32% ) , cardiac surgery in 5 patients ( 20% ) , cerebral angiography in 3 patients ( 12% ) , non - surgery in 4 patients ( 16% ) , seizure in 2 patients ( 8% ) , and other factors , such as damage to the head and peritoneal dialysis , in 3 patients ( 12% ) .\nthere were also cases of temporary cortical blindness reported after post - cardiac surgery angiography . in the case of children ,\nthe early indicators of brain damage after surgery are age , the complexity of surgery , metabolic acidosis , increase in lactate , and artery acidosis . diagnosing cortical blindness is simple when the patient makes a complaint but as in our case , a pediatric patient has limited ability to communicate . therefore , conducting an eeg , fvep , angiography , and funduscopy can assist in making a diagnosis . in this case , the eeg did not show the abnormal finding of a loss in alpha rhythm . however , computed laminography revealed an infarction in the occipital cortex\nwe checked for visual loss with light and objects to test the patient 's avoidance response but he did not respond properly .\nhowever , microemboli caused by extracorporeal circulation can obstruct the blood flow in the cerebral vessels , particularly in the watershed area .\nbraekken et al . reported that cardiac surgery using extracorporeal circulation causes microemboli in most cases .\nin addition , in patients with neural damage , there are more cases of transcranial doppler detection of microembolic signals in the right middle cerebral artery than in patients without .\nmicroemboli mid - surgery occurs most often when blocking the aorta ( 18% ) and unblocking the aorta ( 13% ) .\nrodriguez and belway stated that in pediatric cardiac surgery , the likelihood of microemboli can increase with increasing time of extracorporeal circulation depending on the oxygenator , circuit , adnexa parts , and components .\nthe surgery in this case was not complicated , but may have increased the likelihood of microembolization due to the long extracorporeal circulation time .\nhowever , we should have been more careful in the selecting the -stat and ph - stat method .\nnevertheless , the strength of the ph - stat should have been considered regarding neural sequelae .\nthe cpb priming solution in pediatric patients , unlike adults , can cause blood thinning , which can lead to possible ischemic organ failure .\naldrich et al . reported that conditions , such as the age below 40 , no diabetes or high blood pressure , and no impairment in cognitive skills , language skills or memory , indicate a good prognosis for visual recovery .\nin addition , eeg tests can assist in a diagnosis but are not helpful in accurately predicting the prognosis . in this study ,\ntwo weeks after the surgery , he recovered his speech and cognitive skills , so we did expected a good prognosis .\nthe patient 's vision recovered rapidly from postoperative day 28 and he could be discharged .\nother tests such as a fvep were not performed , so the precise extent of the recovery rate is unknown .\nconsiderable effort is required to reduce neural sequelae after pediatric cardiac surgery , such as visual loss .\nthe cpb machine 's circuit components and type choice should be made on what can best prevent the likelihood of emboli .\na pediatric transesophageal scan and cerebral oxymeter can help in the early identification of neural side - effects .\na transesophageal scan plays an important role in eliminating emboli , so it should be prepared for all suitable pediatric patients .\nthe pathological difference between an adult and pediatric cardiopulmonary bypass should be recognized , and proper measures should be followed .\nwhen cortical blindness is suspected , the ophthalmologist and neurologist should perform a combined examination , being cautious of permanent sequelae . in conclusion , with the reported visual loss in our pediatric patient , surgeons should consider the possibility of visual loss and cerebrovascular injury after a cardiac surgery using cardiopulmonary bypass .", "answer": "visual loss occurring after pediatric cardiac surgery employing cardiopulmonary bypass ( cpb ) is relatively rare but the risk is substantial . \n compromised cerebral perfusion due to a cpb related micro - embolization and inflammatory vascular changes as well as reduced oxygen carrying capacity in hemodilution and hypothermia during cpb might be major contributing factors to the development of postoperative visual loss after cardiac surgery with cpb . \n a case of immediate but transient postoperative visual loss was encountered in a 21-month - old male who underwent tricuspid valve surgery . despite routine intraoperative measures to maintain an adequate perfusion pressure throughout the procedure , postoperative computed tomography revealed a subacute infarct in his occipital lobe . \n recovery began on postoperative day 28 , and the patient 's vision was restored by 31 days .", "id": 261} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\non april 21 , 2008 , three whooper swans ( 2 adults and 1 juvenile ) were found dead at lake towada , akita prefecture , japan ( figure 1 ) .\nit was taken to the wildlife protection center in akita but had to be euthanized that day in moribund status .\nhomogenates from the tracheas , cloacas , and internal organs of 3 swans were pooled and inoculated into embryonated chicken eggs for virus isolation .\nmap of japan and nearby countries , with enlargement of the northern part of the country ( inset ) showing location of lake towada .\nagents were confirmed to be type a influenza viruses by a commercial rapid antigen assay kit and were excluded from being newcastle disease virus by the hemagglutination inhibition test with newcastle - specific antiserum .\nafter those tests conducted at the animal hygiene service center , viruses were brought to the national institute of animal health , tsukuba , japan , for further analysis .\nthe viruses were subtyped as h5n1 with a panel of antiserum , and 1 yielded from cloaca homogenates was designated as a / whooper swan / akita/1/2008 ( wsak08 ) and was further analyzed .\nwsak08 was shown to be highly pathogenic to chickens by an intravenous administration of 10-fold diluted infectious allantoic fluid .\nthis result coincides with the sequence analysis of the hemagglutinin ( ha ) gene , showing that the ha protein possesses a series of basic amino acids ( pqrerrrkr ) at the cleavage site .\nphylogenetic analysis of the ha1 region of the ha gene ( figure 2 ) showed that wsak08 belongs to clade 2.3.2 and is clearly distinguishable from the hpaivs previously isolated in japan in 2004 , a / chicken / yamaguchi/7/2004 ( clade 2.5 ) , and in 2007 , a / chicken / miyazaki / k11/2007 ( clade 2.2 ) . although sequence data were not found in genbank , a / common magpie / hong kong/5052/2007 reportedly resides in the same clade ( 9 ) .\nantigenic analysis of wsaki08 with a panel of antiserum and monoclonal antibodies showed low reactivity against antibodies in the panel ( appendix table ) . a > 32-fold reduction from homologous titers of all hyperimmune serum used\npostinfection duck serum against a / chicken / yamaguchi/7/2004 and a / chicken / miyazaki / k11/2007 did not react with wsak08 .\nnone of the monoclonal antibodies against ha protein of a / chicken / yamaguchi/7/2004 reacted with wsak08 .\nthus , wsak08 is genetically and antigenically distinguishable from the hpaivs that caused previous outbreaks in japan .\nphylogenetic tree constructed based on the hemagglutinin ( ha ) 1 region ( 966 bp ) of the ha gene of the highly pathogenic avian influenza viruses ( h5n1 ) .\nclade designation follows the criteria proposed by the world health organization / world organisation for animal health / food and agriculture organization h5n1 evolution working group ( 8) .\nrepresentative strains of the previous highly pathogenic avian influenza outbreaks in japan are in boldface .\nab436731ab436738 ) showed that it does not contain amino acid substitutions conferring resistance to adamantane or neuraminidase inhibitors . unlike many isolates related to qinghai lake strains that have spread worldwide\nthe neuraminidase protein has a 20-aa deletion at aa 49 to 68 in the stalk region .\nnonstructural protein 1 has a 5-aa deletion at aa 80 to 84 , commonly observed in currently circulating hpaivs ( h5n1 ) in southeastern asia .\nwhooper swans breed in northern eurasia and winter in europe and eastern asia i.e. , china , the korean peninsula , and japan . in japan\n, 35,00038,000 whooper swans spend every winter primarily in hokkaido , tohoku , and the hokuriku area ( 10 ) . in the lake towada area , 300 whooper swans arrive beginning in late october ; they leave the area between late march and late april ( 11 ) . in late march , summer birds begin to arrive . according to results of satellite tracking of 8 swans ( 12 ) , as well as the results of banding studies since 1961 ( 13 ) ,\nwhooper swans that winter in japan migrate from the northern end of honshu island to eastern hokkaido , by means of sakhalin , and reach eastern siberia , where they breed . to our knowledge , there have been no reports of whooper swans that winter on the eurasian continent migrating north through japan . in light of the migratory route mentioned above , the whooper swans found dead at lake towada were most likely recently infected with hpaiv ( h5n1 ) in japan .\nit is unlikely that the swans were infected before they flew to japan in autumn , maintained the virus within the flock , and then suddenly developed the disease after no apparent infections for several months .\nalthough the susceptibility of a certain species of birds to a subtype h5n1 virus may be different depending on the virus strain ( 14 ) , whooper swans as well as mute swans have been considered to be susceptible species to hpaiv ( h5n1 ) , as they showed a fulminant course of disease at the outbreak in germany in 2006 ( 7 ) .\nthe possibility that the swans were infected by domestic fowl is low because there has been no report of hpai among domestic fowl in japan since the beginning of 2008 .\none possible explanation is that other wild birds brought the virus from outside the country .\nalthough it is not known whether any birds wintering on the continent migrate north through japan , passage visitor birds such as wader birds migrate from south to north through japan in spring ; summer birds , e.g. , egrets , swallows , songbirds , and some raptors , come to japan from the south in spring for breeding .\nalso , the possibility of anthropogenic introduction of virus , such as by inappropriate importation of birds , meats , or materials , can not be excluded . in conclusion\n, genetic analysis demonstrates that the virus that killed the 4 swans in japan in 2008 is genetically distinguishable from the strains that caused previous poultry outbreaks in japan , ruling out a possibility of resurgence of previously introduced hpaiv in japan . after the incident we describe\n, 2 other whooper swan cases of hpaiv ( h5n1 ) infection were confirmed in eastern hokkaido in early may .\npossible involvement of wild birds in the introduction of the virus to japan requires further scrutiny .\nantigenic analysis of whooper swan / akita/1/2008 highly pathogenic avian influenza virus ( h5n1 ) versus related isolates *", "answer": "on april 21 , 2008 , four whooper swans were found dead at lake towada , akita prefecture , japan . \n highly pathogenic avian influenza virus of the h5n1 subtype was isolated from specimens of the affected birds . \n the hemagglutinin ( ha ) gene of the isolate belongs to clade 2.3.2 in the ha phylogenetic tree .", "id": 262} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbenign recurrent intrahepatic cholestasis ( bric ) is an autosomal - recessive cholestatic disorder which was first described by summerskill and walshe in 1959 in two patients with recurring cholestasis [ 2 , 3 ] .\nten years later , tygstrup and jensen formulated the defining criteria as : ( 1 ) several episodes of pronounced jaundice with severe pruritus separated by symptom - free intervals lasting several months or years , ( 2 ) absence of a factor known to produce intrahepatic cholestasis ( e.g. drug intake , pregnancy , intoxication ) , ( 3 ) biomechanical signs of obstructive jaundice but with normal intrahepatic and extrahepatic bile ducts ( visualized by cholangiography ) , and finally ( 4 ) bile plugs within ducts in histological specimens [ 1 , 2 , 4 , 5 ] .\npreviously , summerskill - walshe - tygstrup syndrome has been regarded as an idiopathic disease [ 1 , 2 ] .\nmeanwhile it is known that bric displays a genetic heterogeneity and is associated with mutations in the atp8b1 ( bric 1 ) and abcb11 ( bric 2 ) genes and belongs to the canalicular transport defects .\nas it typically does not lead to liver cirrhosis , it is considered as a benign liver disease .\nfor the right diagnosis , both clinical and pathological features are pivotal [ 5 , 6 ] .\ntherapeutically , in moderate cases , conservative treatment with cholestyramine , rifampicin [ 6 , 7 , 8 ] , steroids , phenobarbital , ursodeoxycholic acid or 5-adenosylmethionine may be applied . in more severe cases , a nasobiliary drainage tube can be inserted , or surgical interventions such as partial biliary diversion or ileal bypass may be performed to relieve the patient 's suffering . despite these various possibilities , in some patients symptoms mostly pruritus may still be resistant [ 5 , 9 ] . for such severe cases ,\nnew therapeutic approaches are required to avoid liver transplantation as the ultimate required therapy . in 1988 , several attempts succeeded in lowering bile acids by plasmapheresis [ 10 , 11 ] .\nadditionally , since 2001 , albumin dialysis ( molecular adsorbent recirculation system , mars ) has been successfully applied to improve these patients medical condition and to significantly reduce serum bilirubin and bile acid levels [ 8 , 12 , 13 ] . in the case of our patient , the extracorporeal liver assist device prometheus ( fresenius medical care , bad homburg , germany ) , which is frequently used in patients with severe\ncholestasis or liver failure as a bridging procedure to transplantation [ 14 , 15 ] , has been applied to resolve therapy - resistant pruritus .\nwe report a 45-year - old caucasian woman with summerskill - walshe - tygstrup syndrome which was first diagnosed in 1998 . despite extensive conservative therapy with prednisolone ( 510 mg / day ) , ursodeoxycholic acid ( 3 500 mg / day ) and cholestyramine ( 3 4 g / day )\n, she suffered from intermittent attacks of cholestatic jaundice , severe pruritus and anxious nervousness . on clinical examination\nusually , serum bile acids were elevated at 22.5 2.7 mol / l ( normal\n< 6 mol / l ) , while transaminases as well as -glutamyltransferase ( -gt ) and alkaline phosphatase ( ap ) remained at approximately normal values ( < 35\ne , cmv , ebv and hsv ) and immunological serology ( ana , ama , anca , sma , sla , lkm , -globulin and igg / igm ) were all negative .\nhowever , both the patient 's grandmother and mother suffered from cholecystolithiasis . in march 2008\nultrasound examination revealed normal liver morphology without signs of obstructive cholestasis ( diameter of the common bile duct 3 mm ) .\nadditionally , a liver biopsy was performed which demonstrated normal hepatocyte architecture without inflammatory cells or bile plugs within the canaliculi ( fig .\nthe first 3 dialysis cycles were performed in april 2008 , followed by another 5 cycles in june 2008 , leading to complete recovery and decreasing laboratory parameters . in the following years\n, bile acids were lowered significantly by 78% from an average of 22.5 2.7 to 7.3 1.7 mol / l ( p = 0.003 ) . due to cicatrization of the dialysis catheter , a cimino - brescia fistula was finally applied in january 2011 .\nwe here report a patient with characteristic features of bric , occurring frequently with insistent symptoms . she suffered from intermitting severe pruritus as well as infrequent jaundice .\nthis disease is remarkable for its discrepancy between a rise in serum bile acids at the onset of each attack and a later rise in total serum bilirubin levels . due to conservative treatment with prednisolone ( 510 mg / day ) , ursodeoxycholic acid ( 3 500 mg / day ) and cholestyramine ( 3 4 g / day ) ,\nin contrast , conservative treatment did not have any positive effects on agonizing pruritus . during this stage\n, laboratory parameters revealed the typical periodic elevation of total serum bilirubin and bile acids .\nhowever , transaminases , ap and -gt were less affected ( < 35 u / l ) . whenever intractable pruritus appeared , liver dialysis using the prometheus system was performed .\nthe first cycle was set after worsening of the patient 's condition when a 7 fr nasobiliary drainage tube dislocated in march 2008 . in the following years\n, 3 up to 5 cycles of liver dialysis per session were necessary to normalize laboratory parameters and relieve the patient 's suffering .\nthis range for dialysis sessions is in accordance with other studies describing the application of prometheus in patients with insistent pruritus [ 16 , 17 , 18 ] .\nthe pathogenesis of cholestatic pruritus is not completely clear . besides bile acids , which apparently seem to play a major role as pruritogens , elevated levels of endogenous opioids and amphiphilic lysophosphatidic acid ( lpa )\nin contrast to bile acids , lpa and autotaxin ( the enzyme responsible for the transformation of lysophosphatidylcholine into lpa ) plasma levels were demonstrated to correlate significantly with the severity of patients pruritus .\nconservative treatment is based upon this knowledge as e.g. the bile acid sequestrate cholestyramine is recommended as the first - line treatment by easl and aasld .\ninvolvement of the opioid system furthermore allows the application of opioid antagonists such as naltrexone to resolve pruritus . reported positive effects of the serotonin re - uptake inhibitor sertraline\nactually indicate an involvement of the serotonin system . despite these numerous mechanisms by which the pathogenesis of pruritus can already be affected therapeutically to relieve the majority of patients from pruritus , some of them remain resistant to these therapies . as severe pruritus\nmay lead to reduced quality of life and even to suicide [ 16 , 17 ] , the necessity for an effective therapy becomes obvious .\nin these patients , e.g. with primary biliary cirrhosis , liver transplantation may become the ultimate therapeutic option . until now\n, several studies have provided evidence for extracorporeal liver support systems , first for mars and later for prometheus , to be an effective and safe therapeutic alternative for patients with cholestatic pruritus [ 8 , 12 , 13 , 16 , 17 ] . with regard to the elimination of albumin - bound molecules such as bilirubin ( strongly albumin - bound ) or bile acids ( less tightly albumin - bound ) , there are slight differences between these two methods .\nkrisper and stauber characterized the dialysis performance of prometheus as less selective to albumin - bound molecules and more efficient at the same time as compared to mars . concerning bile acid removal , stadlbauer et al\n. found similar efficiency for both prometheus and mars , while a change in the particular bile acid profile towards hydrophobic bile acids was observed only under prometheus treatment .\nbesides changes in white blood cell count , no adverse effects have been reported so far [ 18 , 22 ] .\nbecause of its rareness summerskill - walshe - tygstrup syndrome is first considered in the differential diagnosis of cholestasis after many years of extensive investigations .\nhowever , in some cases , prometheus liver dialysis appears to be a beneficial alternative for patients with bric - related symptoms mainly intractable pruritus", "answer": "summerskill - walshe - tygstrup syndrome is a rare benign chronic liver disease characterized by recurring cholestasis with jaundice and severe pruritus . due to insufficient conservative treatment , liver dialysis by prometheus \n was applied to a 45-year - old female patient with resistant pruritus . \n initially , other possible liver diseases were excluded and the patient was treated symptomatically since the diagnosis of summerskill - walshe - tygstrup was stated in 1998 . as conservative and endoscopic methods progressively failed to relieve the patient 's suffering , prometheus liver dialysis was performed regularly since 2006 at 3-month intervals and successfully led to a decrease in the patient 's symptoms . \n cholestatic liver enzymes and also serum bile acids could be lowered significantly from an average of 22.5 2.7 to 7.3 1.7 mol / l . \n consequently , prometheus liver dialysis may be a beneficial option for patients with benign recurrent intrahepatic cholestasis suffering from therapy - resistant symptoms and may be used as well as other extracorporeal liver support devices which have already been reported to improve cholestatic pruritus .", "id": 263} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbidirectional ventricular tachycardia ( bvt ) is defined as a tachycardia showing beat - to - beat alternation in the qrs axis .\nthe rate is typically between 140 and 180 bpm , with a frontal plane axis varying between 20 and 110. the most common causes of bvt include catecholaminergic polymorphic ventricular tachycardia and cardiac glycoside toxicity .\nother previously described etiologies include myocarditis , long qt syndrome type 7 , congenital cardiomyopathies , cardiac tumors , and acute cardiac allograft rejection .\ncardiac sarcoidosis is characterized by myocardial inflammation and interstitial fibrosis that can lead to slowed conduction and macro re - entrant arrhythmias .\nwe report a case of bvt in a patient with cardiac sarcoidosis and briefly discuss the proposed mechanisms underlying bvt .\na 73-year - old man with history of chronic pulmonary sarcoidosis was seen for an annual checkup , during which ventricular bigeminy was identified on a 12-lead electrocardiogram .\nsubsequent holter monitor assessment showed multiple premature ventricular beats and several short runs of non - sustained ventricular tachycardia ( vt ) , with two different qrs morphologies ( fig .\n1 ) . a cardiac magnetic resonance tomography with delayed gadolinium showed a curvilinear region of patchy mid - myocardial enhancement within the inferolateral left ventricular myocardium near the base , consistent with cardiac sarcoidosis ( fig .\n2 ) . the left and right ventricular ejection fractions were 47% and 37% , respectively .\na nuclear myocardial perfusion study using single - photon emission computed tomography showed no myocardial perfusion defects on stress or rest imaging , ruling out ischemia .\na fasting 18-fluorodeoxyglucose positron emission tomography ( pet ) demonstrated increased uptake in the same area of the myocardium that had shown late gadolinium enhancement , consistent with active cardiac sarcoid ( fig .\nthe patient was elected to have an implantable cardioverter defibrillator ( icd ) placed for prevention of sudden cardiac death .\nhe had not experienced any vt episodes during the one - year follow - up .\none of the proposed mechanisms of bvt include elevated intracellular calcium , causing delay after depolarization in anatomically separate parts of the conducting system .\nproposed that two separate foci , with different rate thresholds for delayed after depolarization induced ventricular bigeminy , were present in a rabbit model .\nthis would effectively double the heart rate , increasing the overall ventricular rate above the second threshold .\nonce this had developed , the two competing sites would simply alternate on a beat - to - beat basis .\nthis is likely the mechanism underlying bvt observed with digitalis toxicity and catecholaminergic polymorphic vt .\nthe other proposed mechanisms for bvt include an alternating bundle branch block related to bifocal automaticity and inscribed in opposite directions , or scar - mediated reentry around a circuit with two alternating exit sites .\ndescribed a mechanism including retrograde conduction over the mid septal fascicular pathway , with alternating block in the left anterior or posterior fascicles , to explain polymorphic fascicular vt patterns .\nscarring is typically patchy , with a predilection for the basal septum , anterior wall , and perivalvular regions of the left ventricle .\nit may also be confluent , affecting the right ventricular epicardium or endocardium . in sarcoidosis , it is plausible that multiform or bidirectional premature ventricular contractions ( pvcs ) are due to multiple exits from the areas of inflammation and/or scarring .\nconduction disturbances in cardiac sarcoidosis are not uncommon , and often affect the his - purkinje system . in our case ,\nthe patient had an intraventricular conduction delay at baseline , with prolonged qrs complexes at relatively low atrial rates ( fig .\nthe majority of the retrospective data suggest that immunosuppression reduces the burden of arrhythmias , especially in the early phases of the disease .\nprevious case series have reported various success rates with vt ablation in patients with cardiac sarcoidosis , likely due to the small number of patients in each series , with varying degrees of disease burden .\nthe most common circuit for vt in one report was reentry in the peritricuspid area , which can be safely ablated . in another study , abolishing all inducible tachycardias was not always feasible because of septal intramural circuits , extensive right ventricular scarring , or sites of origin in close proximity to the left anterior descending , the ramus intermedius arteries , or the para - hisian region , which prohibit safe ablation . in the current case , it is likely that the presence of a septal focus leads to alternate exits into the right or left ventricle which shows the observed electrocardiogram pattern .\nalthough the septal involvement was not visible by imaging until a year after diagnosis , it might have been present initially , but was microscopic in nature .\nthis is consistent with previous autopsy studies that have shown a heterogeneous distribution of sarcoid granulomas in the myocardium .\nthe recent expert consensus document is an excellent resource for management and risk stratification for cardiac sarcoidosis patients .\nicd implantation for primary prevention is commonly performed due to the high burden of vt events ( estimated incidence rate of 15% per year ) in patients with cardiac sarcoidosis . in the current case ,\nicd implantation was recommended due to the high burden of nonsustained vt episodes , left and right ventricular dysfunction , and the presence of fibrosis and active inflammation by imaging studies .", "answer": "a 73-year - old man with history of pulmonary sarcoidosis was found to have runs of non - sustained bidirectional ventricular tachycardia ( bvt ) with two different qrs morphologies on a holter monitor . \n cardiac magnetic resonance delayed gadolinium imaging revealed a region of patchy mid - myocardial enhancement within the left ventricular basal inferolateral myocardium . \n an 18-fluorodeoxyglucose positron emission tomography ( fdg - pet ) showed increased uptake in the same area , consistent with active sarcoid , with no septal involvement . \n follow - up fdg - pet one year later showed disease progression with new septal involvement . \n cardiac sarcoidosis , characterized by myocardial inflammation and interstitial fibrosis that can lead to conduction system disturbance and macro re - entrant arrhythmias , should be considered in differential diagnosis of bvt . \n bvt may indicate septal involvement with sarcoidosis before the lesions are large enough to be detected radiologically .", "id": 264} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is estimated to be the most common cause of neonatal hospital readmission in north america ( 1 ) .\nit may lead to bilirubin accumulation in basal ganglia and brain stem nuclei and lead to kernicterus .\nif the infants survive the acute phase , which is marked by lethargy , hypotonia , poor feeding and opisthotonus , they may develop chronic encephalopathy .\nthis condition is manifested by cerebral palsy , sensory neural hearing loss , dental dysplasia , upward gaze paralysis and mental retardation ( 2 ) . \n \n\ncauses of severe neonatal hyperbilirubinemia are categorized either as hemolytic ( blood group mismatch , sepsis , g6pd deficiency ) or non - hemolytic ( breast feeding jaundice , internal hemorrhage , gestational diabetes , pyloric stenosis , hypothyroidism and some mutations in hepatic enzymes ) .\nprematurity , jaundice in the first 24 hours of life , jaundice noted before discharge from hospital , a history of jaundice treated with phototherapy in siblings and asian race are other predisposing factors for severe hyperbilirubinemia noted by various studies ( 3 - 5 ) . \n \n\nhowever , severe hyperbilirubinemia is mainly treated by exchange transfusion ( et).according to american academy of pediatrics ( aap ) , neonates with weight 2500 grams in healthy term , et is indicated when indirect bilirubin level reaches 25 mg / dl and 20 mg / dl and in cases with risk factors or gestational age of35 - 37 wk and well despite 6 hr of intensive phototherapy . in newborns of 35 - 37 wk and risk factors , et is indicated when the indirect bilirubin level reaches 18 mg / dl despite 6 hr of intensive phototherapy ( 2 ) .\net is associated with many complications such as hypersensitivity reactions , sepsis , catheter - induced vascular damage , hypotension , necrotizing enterocolitis , etc ( 5 ) . \n \n\nthe present study has been conducted to investigate the causes of severe hyperbilirubinemia leading to exchange transfusion from march 2009 to march 2011 in bahrami children hospital , tehran , iran .\nthe aim was to identify neonatal predisposing factors that can be prevented by screening or other measures , thus reducing the incidence of kernicterus , which can be prevented and also to avoid et and its side effects . \n\n\n all infants below 30 days who underwent et for severe hyperbilirubinemia in bahrami children hospital during 2009 - 2011 were enrolled into this cross sectional study . a questionnaire prepared consisted of neonates gender , gestational age , age at the time of admission , birth weight , time of jaundice appearance , history of severe hyperbilirubinemia in siblings , blood group and rh of both mother and neonate , g6pd activity , complete blood count , reticulocyte count , peripheral blood smear , total and direct bilirubin before and after exchange transfusion , direct coombs in mother and indirect coombs in neonates , times of transfusion , any other diagnostic laboratory data based on attending neonatologist 's decision and the cause of hyperbilirubinemia stated by the attending neonatologist .\ncriteria for diagnosis of abo incompatibility were type o maternal blood group and a , b or ab neonatal blood group associated with neonatal hb drop .\npositive coombs , peripheral blood spherocytosis and high corrected reticulocyte count were other diagnostic criteria .\nicteric breastfed newborns with the beginning of jaundice in the second or third day of life and 2% or more weight loss per day of life with or without uremia or hypernatremia were considered breastfeeding jaundice . \n \n\n\n during the study period , 94 neonates ( 56.4% boys and 43.6% girls ) underwent exchange transfusion due to severe hyperbilirubinemia .\nthe infants had a mean birth weight of 195040 g and a mean gestational age of 35.21.4 weeks .\nfifty nine ( 63% ) of neonates were preterm , and history of neonatal jaundice in siblings was reported in 50% of cases .\nhowever , only 18(19% ) had a history of severe hyperbilirubinemia leading to et in their siblings . \n \n\nmost cases ( 40.5% ) of severe hyperbilirubinmia started to become icteric on the second day after birth . \n \n\nfirst day jaundice was observed in 10 neonates , all of them due to hemolysis .\ntable 1 shows a summary of underlying factors for severe hyperbilirubinemia according to the onset of jaundice . \n \n\nthe majority of infants ( 91.5% ) had only one episode of et , and hemolysis was the sole underlying reason in the remaining who had 2 or 3 episodes of et .\ntotally , after prematurity , the second most prevalent underlying factor for severe hyperbilirubinemia was breastfeeding jaundice that included 33(35% ) of neonates .\nwe found that the next most prevalent causes were abo mismatch and g6pd deficiency ( table 2 ) .\nthere was no kriglernajar cases in our study because no significant hyperbilirubinemia was found after discharging and fallow up . \n\n\n according to epidemiological studies , some risk factors are associated with severe hyperbilirubinemia in neonates .\nthe risk factors are male gender , jaundice presenting in the first 24 hours after birth , jaundice noted at discharge from the hospital , previous sibling with jaundice , preterm labor , breast feeding , rh and abo incompatibility , g6pd deficiency and sepsis ( 4,6 ) . \n \n according to the canadian pediatric society\n, gestational age of 35 - 36 weeks is an important risk factor for hyperbilirubinemia ( 7 ) .\nkuzniewicz et al also reported gestational age to be the main predictor of severe hyperbilirubinemia ( 8) . in our series , infants had a mean gestational age of 35.2 weeks and fifty nine ( 63% ) of neonates were preterm . \n \n\nmost cases ( 40.5% ) of severe hyperbilirubinmia started on the second day after birth .\nthis corresponds with views of american academy of pediatrics and canadian pediatric society , which recommend clinical assessment of infants for jaundice within the first 48 hours of birth ( 6 , 7 ) . however , clinical assessment of newborns is not an accurate means of assessing the severity of hyperbilirubinemia ( 1 ) . \n \n in the present study ,\nbreastfeeding jaundice , as the most important factor associated with severe hyperbilirubinemia and according to salas and mazzi ( 9 ) , is encountered in 33(35% ) of cases .\nthe data also corresponds with findings of huang et al ( 6 ) , who reported an odds ratio of 3.2 for severe hyperbilirubinemia in neonates who were breastfed ( 10 ) .\nguidelines advise mothers to nurse their infants at least 8 to 12 times per day for the first several days , rooming in with night feeding , discouraging 5% dextrose or water supplementation and ongoing lactation support for reducing the incidence of breast feeding jaundice ( 2 ) . \n \n in this study ,\nabo mismatch was the third most common cause of severe hyperbilirubinemia and accounted for 24.5% of cases .\nthis is similar to the reports of badee and sanpavat who reported abo mismatch in 22% and 21.3% of cases , respectively ( 11 , 12 ) .\nhowever , according to canadian surveillance program , the most common causes of severe hyperbilirubinemia were incompatibility abo blood group and g6pd deficiency . \n \n\nthe g6pd deficiency was the fourth most prevalent risk factor for severe hyperbilirubinemia leading to et and accounted for 12(12.8% ) of cases .\nbadee also reported g6pd deficiency in 19.1% of neonates who underwent et ( 11 ) . according to johnson\net al , g6pd deficiency was considered to be the main cause of hyperbilirubinemia in 19 of 61 ( 31.5% ) infants who developed kernicterus ( 14 ) . \n \n\nsepsis was the most common underlying cause for et in the study performed by koosha and rafizadeh ( 15 ) . \n\n\n prematurity was the most prevalent risk factor for severe hyperbilirubinemia . thus following protocols for prevention of premature labor\nis recommended . educating mothers for breast feeding in regard to the right times and method of feeding are important issue that should be considered . since blood group mismatch and g6pd deficiency\nwere the third and fourth most prevalent underlying factors , screening infants for blood group and if proven to be cost effective , g6pd activity in the first day of life are also recommended . arranging earlier and continuous visits in neonates with these risk factors during the first four days of life are also mandatory .", "answer": "background : severe neonatal hyperbilirubinemia is associated with significant morbidity and mortality . \n this study was conducted to investigate the causes of severe hyperbilirubinemia leading to exchange transfusion ( et ) from march 2009 to march 2011 in bahrami children hospital , tehran , iran in order to establish guidelines to prevent profound jaundice & et . \n\n \n methods : 94 neonates underwent et for severe hyperbilirubinemia data for demographic data , and onset of jaundice , history of severe hyperbilirubinemia in siblings , blood group of both mother and neonate , g6pd activity , hemoglobin , hematocrite , reticulocyte count , peripheral blood smear , total and direct bilirubin before and after et , direct and indirect coombs , times of transfusion and the cause of hyperbilirubinemia were all recorded for analysis . \n\n results : ninety four neonates ( 56.4% boys and 43.6% girls ) underwent et with a mean birth weight of 195040 g and a mean gestational age of 35.21.4 weeks . \n premature labor , breastfeeding jaundice , abo incompatibility and g6pdd with the frequency of 59(63% ) , 33(35% ) , 25(24/5% ) and 12(12.8% ) were of major causes of et . \n\n \n conclusions : predisposing factors for severe hyperbilirubinemia in this study were premature labor , breastfeeding jaundice , abo incompatibility and g6pdd . the authors recommend prevention of premature labor , reevaluation of successful breastfeeding education for mothers and screening infants for blood group and g6pd in the first of life . arranging earlier and continuous visits in neonates with these risk factors during the first four \n days of life is also recommended .", "id": 265} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan adrenal incidentaloma is an adrenal mass , larger than 1 cm in diameter , detected on imaging studies performed for other indications than adrenal disease [ 1 , 2 ] .\nthe increasing use of computed tomography ( ct ) scans and magnetic resonance imaging ( mri ) causes a marked increase in incidence of adrenal incidentalomas . in approximately 6% of all autopsies and 4% of all abdominal\nct scans an incidentaloma of the adrenal gland is discovered [ 4 , 5 ] . the incidence of adrenal incidentaloma increases with age to an incidence of 10% in patients over 70 years old .\nadrenal incidentalomas are characterized by size , growth , imaging characteristics , and functional status .\nalthough rare , the normal function of the adrenal gland can be disrupted by adrenal incidentalomas . in most cases adrenal incidentalomas will be a small , nonhormonal active cortical adenoma , a benign impediment ( 80% ) .\nsome adrenal incidentalomas cause hormonal hypersecretion ( 15% ) or appear to be a primary or secondary malignancy ( < 5% ) [ 6 , 7 ] . \nadrenal incidentalomas can cause disease by hypersecretion of hormones . conditions due to hormonal activity of adrenal incidentaloma include hypercortisolism , ( cushing 's syndrome ) , catecholamine excess ( pheochromocytoma ) , or hyperaldosteronism ( conn 's syndrome ) .\nsubclinical autonomous cortisol hypersecretion is the most frequent hormonal abnormality in patients with adrenal incidentalomas .\nsome of these patients eventually develop overt clinical cushing 's syndrome . adrenal cortical adenomas with or without hormonal overproduction\nvascular lesions of the adrenal are suggestive of a medullary derived pheochromocytoma , but confirmation of a pheochromocytoma by serum or urine measurement of metanephrines is required to diagnose pheochromocytoma .\nnot only will the radiologist appoint this finding in the radiology report , the radiologist will often also add a recommendation for the next diagnostic procedure .\nthis retrospective study aims to get a clear view on the detection rate of adrenal incidentalomas on abdominal ct scans in our hospital , and the subsequent diagnostic procedures used after detection of this incidental finding .\nthis retrospective study was designed to investigate the detection rate of adrenal incidentalomas on abdominal ct scans . for inclusion in this investigation ,\nan adrenal incidentaloma was defined as an adrenal mass , greater than 1 cm in diameter , initially discovered by diagnostic imaging for a clinical condition not related to , or suspicious for , adrenal disease .\ntwo investigators learned from an expert radiologist to examine ct scans of the abdomen for primarily the adrenal gland .\neach investigator independently evaluated 180 ct scans out of 360 ct scans , of many patients , that were indicated for diagnostics of hepatic , pancreatic , or renal pathology between 2005 and 2007 .\nage , gender , indication for ct scan , and abnormalities in size or morphology , were noted . at the time of examining the adrenal glands ,\nthe investigators were not aware of the content of ct scans ' radiology report or indication for ct scan . only after their own judgement about size and aspect of the adrenal glands , indication for ct scan and the radiology report\nan expert abdominal radiologist ( over 45,000 abdominal ct scans examined ) reviewed the ct scans marked by the investigators with abnormal adrenal glands in size or morphology and results were compared .\nif an adrenal incidentaloma was mentioned in the original radiology report , the patients ' record was reviewed to determine whether additional investigations , for example , hormonal studies , additional imaging , or interventional diagnostic studies , were performed after the ct . \nan interobserver test was performed to evaluate the resemblance of the way of evaluation between the investigators and expert radiologist .\nthe ct scans performed for suspected hepatic , pancreatic , or renal pathology of 75 new patients , between 2007 and 2008 , were evaluated for this purpose .\nthe interobserver variability was calculated with the friedman test , a non - parametric test for coupled observations , with independent observers .\nof the 360 patients studied , 206 ( 57% ) were men and 154 ( 43% ) were women .\nof the total of 360 patients , 4 patients were excluded because suspected adrenal pathology was also an indication for imaging in these patients . in the remaining 356 ct scans evaluated , the investigators discovered independently a total of 44 ( 12% ) abnormal adrenal glands in 42 patients ( 2 bilateral adrenal incidentalomas ) .\neach radiology report was checked for adrenal incidentalomas which were already noted . in 25 ( 7% ) of 356 patients an adrenal mass\nthe expert radiologist reassessed the ct scans of 42 patients ; the radiologist discovered 17 patients with an adrenal incidentaloma .\ntwo patients had bilateral incidentalomas , giving a total of 19 adrenal incidentalomas not noted previously ( figure 1 ) .\nthe total number of adrenal incidentalomas was 44/356 ( 12% ) in 42 patients . \n\nfigure 3 shows an enlarged right adrenal not mentioned in the initial radiology report . in 64 of 356 ( 18% ) patients , a malignancy was the indication for imaging .\npatients with an adrenal incidentaloma were more likely to have a malignancy as indication for ct scan , 20/42 ( 48% ) . \nthe 25 patients that had an adrenal incidentaloma mentioned in the initial radiology report were checked for additional diagnostic procedures performed . in 3/25 patients a follow - up ct scan\nnone of these patients showed hormonal overproduction caused by the adrenal lesion . in 2 patients ( 8% ) a second ct scan was performed to exclude increase in adrenal size ; there was no growth of the adrenal lesion shown . \none patient who underwent a hemihepatectomy had a simultaneous resection of the right adrenal incidentaloma .\nthe interobserver variation was calculated using a friedman analysis test to exclude or to demonstrate a significant difference in perception between different readers .\nthe friedman test showed that there was no statistically significant difference in perception between the investigators and the radiologist ( p = .867 ) .\nthe detection of adrenal incidentalomas in this study was 7% and the actual incidence of adrenal abnormalities was 12% after focused assessment of ct scans .\nthis is high compared to other studies and can be explained by the relatively large group of patients who underwent imaging examination because of a malignancy [ 7 , 11 ] .\nhowever , because of the absence of histological examination of the enlarged adrenal glands , it can not simply be concluded that these patients had metastases in the adrenal gland .\nthe incidence of adrenal incidentalomas in the literature varies from 0.5% to 15% and depends mainly on the age of the investigated group [ 11 , 12 ] .\nonly 6 of 25 ( 24% ) patients with an adrenal incidentaloma were further investigated with hormonal workup or imaging .\none reason for the lack of additional diagnostic testing and treatment after detection of an adrenal incidentaloma is the lack of a clear evidence based guideline .\nalso unfamiliarity with adrenal incidentalomas by the physician who has requested the ct scan will cause lack of additional screening .\nanother reason for the lack of additional diagnostic testing of adrenal incidentalomas is the apparent lack of direct clinical consequences [ 13 , 14 ] .\nundetected hormonal hypersecretion will probably reveal itself in time and the chance of an adrenal carcinoma is low with 0.72/million / year [ 10 , 13 ] . because of this low risk of malignancy and because of the limited impact of hormonal overproduction in an asymptomatic patient , it is not clear whether a guideline for diagnosis and treatment of adrenal incidentaloma is necessary .\nsuch a guideline may cause an increase in diagnostic procedures with additional burden and uncertainty for the patient .\na comprehensive cost - effectiveness study showed however that hormonal analysis of an adrenal incidentaloma is cost effective .\nthe cost effectiveness of additional imaging of the adrenal gland is less clear in this study .\nin addition , the radiation dose to the patient becomes more important and therefore complementary imaging with an mri scan has its advantage .\nthe optimal strategy for screening and followup of an adrenal incidentaloma is still under discussion .\nthe guideline of the nih ( 2002 ) seems to be the best alternative in this debate , but the nih already recognized that the guideline is not based on hard evidence .\n( table 1 ) protocols on the diagnostic procedures of adrenal incidentalomas are described in several other publications as well , without describing additional prospective data on the clinical results of these protocols [ 9 , 10 , 1518 ] .\nthere are currently no prospective studies that have examined the effects of an additional diagnostic procedure for adrenal incidentalomas . \nfollowing this study a guideline for additional screening and followup was made ( figure 2 ) . in each radiology report a recommendation will be added for every patient with an adrenal incidentaloma and the referring physician is pointed to a webpage with a brief summary about adrenal incidentalomas .\nthis website also contains the brochure with information for patients , which can be printed . in conclusion ,\nit is not always noted by the radiologist and focused assessment of abdominal cts increased the detection rate of this abnormality form 7% to 12% . when detected and mentioned in the radiologist 's report , only a small percentage of patients receives additional hormonal or imaging investigations to determine the nature of the incidentaloma .", "answer": "objectives . the aim of this study was to investigate the detection rate of adrenal incidentalomas and subsequent workup . design . \n retrospective cohort study . methods . \n two investigators evaluated the adrenals on abdominal ct scans . \n abnormalities were compared to the original radiology reports and an experienced abdominal radiologist reviewed the ct scans . all additional imaging and laboratory tests were assessed . \n results . \n the investigators detected 44/356 adrenal incidentalomas ( 12% ) . in 25 patients \n an adrenal incidentaloma had been noted in the radiology report . \n the expert radiologist agreed on 19 incidentalomas in 17 patients , two with bilateral incidentalomas . \n of the 25 incidentaloma patients , 4 ( 16% ) patients were screened for hormonal overproduction and 2 ( 8% ) patients had follow - up imaging studies . \n conclusions . \n 12% of the patients had an adrenal incidentaloma ( 42 of 356 ) . \n 17 ( 40% ) had initially not been reported by the radiologist . \n when diagnosed with an adrenal incidentaloma , only a small percentage of patients ( 16% ) is screened or undergoes repeated imaging ( 8% ) as proposed in the national institutes of health ( nih ) guidelines on adrenal incidentalomas .", "id": 266} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe delicate catheter ablation of atrial fibrillation ( af ) involves a relevant risk of major complications although mortality is less than 1 in 2000 , , .\npatients undergoing catheter ablation for af are required to lie motionless on the procedure table for several hours , and repeated stimuli from ablation are sometimes painful . for these reasons ,\nthe safety of deep sedation in this procedure has already been tested , and high - frequency jet ventilation during general anesthesia has also proved to be a safe technique .\naid for anesthetic management in these setting can be non - invasive ventilation ( niv ) , first used in acute respiratory failure , sometimes during sedation , subsequently used outside of the intensive care unit and in cardio - surgical procedures , , , .\nthe aim of our study was to evaluate the usefulness of niv during sedation in catheter ablation of use af instead of atrial fibrillation compared to deep sedation .\nin the study period ( 24 months ) , conducted in a single high - volume electrophysiology procedure center , consecutive patients undergoing catheter ablation for paroxysmal / persistent atrial fibrillation were retrospectively revised ( fig . 1 ) .\nexclusion criteria for the procedure were left ejection fraction less than 40% , moderate - to - severe mitral valve disease , severe heart failure ( new york heart association functional class iii or iv ) , expected surgery for structural heart disease , secondary af ( due to cardiac surgery , infection or hyperthyroidism ) , severe copd with concomitant respiratory insufficiency ( pao2 < 60 mmhg ) , presence of inducible myocardial ischemia or other acute illness underway , or contraindications to anesthesia . complications and recurrence of af occurring within 48 h of the electrophysiological procedure were also examined .\nperioperative anesthesia visits and sedation procedures were performed according to siaarti ( societ italiana di anestesia analgesia rianimazione e terapia intensiva ) guidelines , , including pulmonary function tests in the anesthetic assessment .\nroutine monitoring ( electrocardiography , pulse oximetry , invasive arterial pressure , seriate arterial blood gas analysis and apnea monitor ) were performed .\nsedation and niv were performed after trans - septal puncture in order to rule out left - sided emboli through neurologic assessment . midazolam\n0.010.02 mg / kg iv was administered immediately before monitoring , fentanyl ( 2.55 g / kg ) was administered as analgesic and sedation was performed by propofol infusion ( bolus dose 11.5 mg / kg , maintenance 24 \nthe infusion rate was carefully titrated to achieve a target sedation level of a ramsay sedation scale of 23 .\nmean arterial pressure was maintained above 75 mmhg during the entire procedure . during deep sedation\n, the patients were breathing spontaneously and were given supplemental oxygen ( fio2 80100% ) to maintain the oxygen saturation level above 92% . in patients undergoing niv ventilation the procedure was performed with a respironic latex - free total face mask connected to garbin ventilator ( linde inc . , herrsching , germany ) in spontaneous / temporized mode applying incorporated algorithms to improve patient - ventilator synchrony by adjusting to changing breathing patterns and dynamic leaks .\ni - pap , e - pap and respiratory rate were modified according to the clinical response , tolerance of the patient to obtaining exhaled tidal volume of 68 ml / kg ; fio2 requirement was 40% or less to maintain oxygen saturation above 92% .\nthe ventilator settings were adjusted on the basis of pulse oximetry and serial measurement of arterial blood gases .\nsedation was halted when the mechanical ventilation was discontinued or at the end of the catheter ablation procedure . at the end of the procedure ,\npatients were transferred , according to hospital protocol , to the intensive care unit for monitoring .\noral anticoagulation with stable international normalized ratio ( inr ) superior to 2.0 was ensured for at least 3 weeks before ablation .\ntransesophageal echocardiography was performed within 24 h before the procedure , to rule out the presence of left atrial thrombi . local anesthesia ( lidocaine 1% )\nafter septal puncture of interatrial septum , intravenous heparin was administered according to institutional standards .\nminneapolis , mn , usa or carto-3 mapping system , biosense webster , diamond bar , ca , usa ) with image integration using computer tomography or magnetic resonance reconstruction of the left atrium .\ncatheter ablation procedure was performed using radiofrequency energy or cryoablation balloon ablation catheter ( arctic front , medtronic , minneapolis , mn , usa ) .\nthe electroanatomic mapping systems and the energy sources used during the procedure were selected by the electrophysiology team in relation to clinical characteristics of the patient .\ncategorical variables were represented as percentages , continuous variables as mean standard deviation .\ncomparisons between groups were performed by unpaired samples two - sided t - test or chi - square test , with continuity correction , where appropriate .\nintra - procedural changes of arterial blood gas variables were expressed as percentage variation of their basal values . a p - value less than 0.05 was considered statistically significant .\nduring the study period 72 electrophysiology procedures carried out in deep sedation were evaluated ; 41 ( 57% ) procedures were performed with niv ( niv group ) and the other 31 ( 43% ) with - out niv ( deep sedation group ) .\nthe clinical characteristics of the patients and the procedural details are shown in table 1 .\nthe two groups of patients showed no differences in these fields , but between the two groups , a significant variation was present in the basal paco2 ( p = 0.008 ) with values in the physiological range and in intra - procedural blood gas parameters ( ph p = 0.001 , pao2 \n p = 0.004 , paco2 \n p = 0.002 respectively ( fig . \nanalysis of the percentage change between basal to intraprocedural blood gas parameters ( fig . \n3 ) shows a statistical variation in the changing of ph and paco2 ( p = 0.002 and 0.001 , respectively ) . during niv procedures\nthere were no problems due to mask - related difficulties , gastric distention , niv discomfort or significant hemodynamic alterations related to positive pressure ventilation . in the deep sedation procedure there were two episodes of respiratory complications with severe hypercapnia ( achieved a paco2 greater than 60 mmhg ) treated with application of niv .\nadverse events , focused on periprocedural complications , were reported in 26 patients ( 36% ) . among the complications , vascular access complications occurred in nine cases ( iatrogenic femoral pseudoaneurysms that required percutaneous treatment in 5 cases and femoral hematoma with decrease in hemoglobin levels greater than 2 g / dl in four cases ) ; none of these cases required transfusion support .\npleuro - pericardial effusion was documented in 8 cases ; exacerbation of bronchial asthma in three cases ; bradyarrhythmia requesting definitive pacemaker implantation in two cases ; pulmonary embolism in one case ; procedural myocardial infarction in one case ; post - procedural stroke in one case and permanent paralysis of the phrenic nerve in one case .\nthe recurrence of af within 48 h of the electrophysiological procedure was recorded in 21 patients ( 29% ) and was treated by electrical or pharmacological cardioversion .\ndeep sedation for catheter ablation of af is feasible and safe while maintaining spontaneous ventilation . in our sedation procedures in catheter ablation of af\nthe niv was safe as well , and maintained ( although with respiratory parameters in the physiological range ) a better homeostasis in these parameters compared to deep sedation in breathing spontaneously . data shown in fig . 2 , fig . \n3 confirmed a lower impact of niv on arterial blood gas tensions and hematic ph balance compared to deep sedation .\nwhile statistically significant differences were found , the absolute value differences had a clinically limited benefit ; using niv made it possible to reduce the flow of oxygen administered to the patient during the procedure and maintain better respiratory dynamics .\nthese conditions allowed us to maintain effective co2 elimination with minimum impact on the ph compared to the deep sedation group .\nfurthermore , in the 2 cases of patients who developed severe hypercapnia during deep sedation , the application of niv was effective in solving the respiratory problem without the need for endotracheal intubation .\nthis data shows an important and clinically relevant difference between the groups , although the small sample size does not allow to compare this end point between the two arms of the study .\ndeep sedation requires frequent control and titration by anesthesiologist due to minor problems such as requiring high oxygen dose , great difference between basal and intraprocedural gas properties and occasional hypercapnia .\nfurthermore , niv allows to reduce the risk of hemodynamic , respiratory or neurological problems secondary to improper ventilation .\nwe did n't have problems related to mask - related difficulties , gastric distention , niv discomfort or significant hemodynamic alterations related to positive pressure ventilation .\nalso , consideration must be given to the demographic characteristics of own patients : our population had a high number of overweight patients ( overweight 39% , obese 25% ) and with a history of smoking ( 44% ) . in relation to these conditions ,\neven when outside the guidelines , , our patients ' baseline respiratory function characterization was performed .\na limit of our study is the relatively small number of patients evaluated , which did not arrive at the number of patients evaluated in other studies that assessed the safety of deep sedation or high - frequency jet ventilation . as previously described , af catheter ablation procedure has substantial procedural risks , , .\nmost of the complications ( 12/26 cases ) that we reported were due to the difficult balance between bleeding ( due to systemic anticoagulation ) and thrombotic ( ablation procedure and recurrence of af ) processes . in our cases\npleuro - pericardial effusion is due to the irritation of the serosa secondary to the ablation procedure as well as paralysis of the phrenic nerve and the damage occurring to the conduction system .\nincidence of major procedural complications ( 5/26 cases ) was comparable to the previous reports , , do not show differences in the two groups and are imputable to electrophysiological procedure rather than anesthetic management . of the minor complications , the only one related to anesthetic management was exacerbation of bronchial asthma .\nwe did not find significant differences between the two anesthetic regimens tested ( two cases in niv group vs one case in the deep sedation group ) .\nthese patients responded rapidly to treatment with inhaled 2-agonists and showed no alterations in chest x - ray compatible with bronchopneumonia .\nown data on the early recurrence of af are in line with the literature , and this event was not related to the long - term success but was due to edema and inflammation of the myocardium subjected to ablation . in relation to the thromboembolic risk of early relapse of af , international guidelines recommend oral anticoagulation therapy in the first few months post - ablation . in conclusion\n, our study suggests that in catheter af ablation , niv proved to be a safe practice in anesthesiological management , as it can treat respiratory depression induced by sedation and maintain better respiratory homeostasis and better arterial blood gas balance when added to deep sedation .\nfurthermore , during the procedure patient safety was also ensured by a ventilator , which allowed continuous control of tidal volume , amount of ventilation lost to leak and effective minute ventilation .", "answer": "anesthetic management of patients undergoing pulmonary vein isolation for atrial fibrillation has specific requirements . \n the feasibility of non - invasive ventilation ( niv ) added to deep sedation procedure was evaluated.seventy-two patients who underwent ablation procedure were retrospectively revised , performed with ( 57% ) or without ( 43% ) application of niv ( respironic latex - free total face mask connected to garbin ventilator - linde inc . ) during deep sedation ( midazolam 0.010.02 mg / kg , fentanyl 2.55 g / kg and propofol : bolus dose 11.5 mg / kg , maintenance 24 \n mg / kg / h).in the two groups ( niv vs deep sedation ) \n , differences were detected in intraprocedural ( ph 7.37 0.05 vs 7.32 0.05 , p = 0.001 ; pao2 117.10 27.25 vs 148.17 45.29 , p = 0.004 ; paco2 43.37 6.91 \n vs 49.33 7.34 , p = 0.002 ) and in percentage variation with respect to basal values ( ph 0.52 0.83 vs 1.44 0.87 , p = 0.002 ; paco2 7.21 15.55 vs 34.91 25.76 , p = 0.001 ) of arterial blood gas parameters . \n two episodes of respiratory complications , treated with application of niv , were reported in deep sedation procedure . \n endotracheal intubation was not necessary in any case . \n adverse events related to electrophysiological procedures and recurrence of atrial fibrillation were recorded , respectively , in 36% and 29% of cases.niv proved to be feasible in this context and maintained better respiratory homeostasis and better arterial blood gas balance when added to deep sedation .", "id": 267} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmelioidosis is predominantly a tropical disease and most cases are reported during the rainy season in endemic area .\nit is characterized by abscess - formation in the lung , liver , spleen , skeletal muscle and prostate with the lung being the most commonly involved organ .\nthe clinical features are variable from rapidly progressing septicemia to chronic debilitating abscess - forming disease .\nunderstanding about melioidosis is important in tuberculosis endemic areas , because its progression and roentgenographic findings are so similar to tuberculosis that it is not rare for melioidosis to be misdiagnosed as tuberculosis .\nthe patient was a 50-yr - old man who was diagnosed with melioidosis on bronchoscopic washing culture and whose symptoms improved after treatment with high dose ceftazidime .\na 50-yr - old man visited our hospital because of intermittent fever associated with cough , sputum , generalized myalgia and general weakness for about four weeks .\nhe had lived in indonesia for twenty years for business , and visited a local hospital in indonesia and was treated for typhoid fever without improvement of symptoms .\ninitial chest radiograph and computed tomography ( ct ) images showed multiple satellite nodules in the left lower and upper lobes , and judging from that roentgenographic examination , tuberculosis was the most probable diagnosis ( fig .\n1 ) . bronchoscopy showed no endobronchial lesion and washing cytology and culture were also negative .\nthree months later we rechecked chest radiograph and ct findings , and found new infiltration in the left lower lobe and improvement of lesions in the left upper and lower lobes ( fig .\nlaboratory findings included white blood cell count of 5,240/l and hemoglobin value of 11.6 g / dl .\niga was 227 mg / dl ( normal range : 90 - 400 mg / dl ) and anti - neutrophilic cytoplasmic antibodies with cytoplasmic staining pattern ( canca ) was negative .\nhowever , secretion was seen in left lower lobe , so washing cytology and culture was done .\ncytology was negative but a species of bacteria grew on blood agar media ( fig .\n3 ) . it was gram - negative , non - spore forming and showed as a safety pin shaped organism on microscopic examination ( fig .\napi20ne strip and vitek gni card ( biomerieux , inc . , hazelwood , u.s.a . ) ,\nthe organism was identified as burkholderia pseudomallei ( 1 ) . on dna sequencing of 16s ribosomal rna , it was compatible with b. pseudomallei with 100% homology and formed a characteristic rugose colony on blood agar .\nwe prescribed ceftazidime 2 g intravenously every 8 hr and he did not complain of intermittent fever any more .\nafter one week of intravenous ceftazidime , he was discharged with oral amoxicillin - clavulanate ( 750 mg every 8 hr ) .\none month later the cough and sputum were almost disappeared but his general weakness persisted although it was also improving .\nfour months later we rechecked chest ct to show an improvement of infiltration in left lower lobe .\nhe said his condition was as good as his previous state before suffering from melioidosis .\none month later , we stopped administrating oral antibiotics to him , which resulted in him taking amoxicillin - clavulanate for total five months .\nthe endemic area includes southeast asia , north australia , madagascar , and guam ( 2 ) . in northeast\nthailand , melioidosis accounts for 20% of all community - acquired septicemias , and causes death in 40% of treated patients .\nmelioidosis was first described by whitmore in 1911 and more than 100 cases had been reported by 1917 ( 3 ) . since then , with sporadic cases being reported during and after world war ii and many soldiers fighting in vietnam suffering from this disease , western countries began to take an interest in melioidosis .\nb. pseudomallei is a motile aerobic , non - spore - forming and gram - negative bacillus .\nthe colonies develop a rugose appearance , and take up crystal violet dye from the medium .\nalthough it is gram - negative bacterium , it is usually resistant to aminoglycoside , 1st & 2nd cephalosporin , macrolide , rifamycin and colistin , but is susceptible to ampicillin / sulbactam , chloramphenicol , tetracycline , bactrim , 3rd cepha and carbapenem ( 4 ) .\nb. pseudomallei is a soil saprophyte and can be recovered readily from water and wet soils in rice paddy fields .\nfor example , in thailand the organism can be cultured readily from more than 50% of rice paddies ( 5 ) .\nit presents as a febrile illness , ranging from an acute fulminant sepsis to a chronic debilitating localized infection .\nthe lung is the most commonly affected organ , either presenting with cough and fever resulting from a primary lung abscess or pneumonia .\nseeding and abscess formation can arise in any organ , and the liver , spleen , skeletal muscle and prostate are common sites .\nlocalized pulmonary melioidosis often can not be differentiated from tuberculosis on clinical and chest radiography findings .\nfirst , some melioidosis cases have rapid clinical and roentgenographic progression within a few days .\nsecond , melioidosis usually responds to treatment well and has apparent roentgenographic improvement within 1 - 2 weeks .\nthird , parapneumonic effusion develops in 5 - 15% of cases , but the amount is not large and associated pulmonary infiltration is always present .\nin contrast , tuberculosis pleurisy in which a large amount of pleural fluid is present without underlying pulmonary infiltration is common .\ndiagnosis of melioidosis is made by isolation of b. pseudomallei from any site ; for example blood , sputum , abscess fluid and throat swab .\nsince splenic abscess is much less common in other diseases , its presence is more likely to suggest melioidosis .\nthe antibiotic of choice is ceftazidime ( 40 mg / kg intravenous injection every 8 hr ) , while other 3rd generation cephalosporin is less effective ( 9 ) .\nfour - drug combination is usually recommended as oral antibiotics , and those are chloramphenicol ( 40 mg / kg per day in four divided doses ) , doxycycline ( 4 mg / kg per day in two divided doses ) , trimethoprim - sulfamethoxazole ( 10 mg and 50 mg / kg per day , respectively , in two divided doses ) .\nhigh dose ceftazidime followed by long term oral antibiotics is considered to be most effective treatment .\nthe distribution and frequency of melioidosis is probably greatly underestimated ( 10 ) . in tuberculosis endemic areas ,\nit is important to understand melioidosis and differentiate this disease from tuberculosis because the treatment of the two diseases is completely different .", "answer": "melioidosis is an infection of the gram - negative bacterium burkholderia pseudomallei . \n while it is known as an important cause of sepsis or chronic abscess - forming disease in southeast asia and northern australia , no case has yet been reported in korea . \n a 50-yr - old man visited our hospital for intermittent fever associated with dry cough and sputum . \n roentgenographic examination showed migrating pulmonary infiltration . \n symptoms and chest radiograph and computed tomography ( ct ) image findings did not improve despite use of fluoroquinolone antibiotics . \n gram - negative bacteria were isolated on bronchoscopic washing culture and were identified as b. pseudomallei on dna sequencing of 16s ribosomal rna with 100% homology . \n treatment for melioidosis was commenced with high dose ceftazidime , and the patient 's fever , cough , and sputum were improved and the lesion on chest radiograph and ct almost disappeared .", "id": 268} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nCopper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light\n\nPaper sections:\n\nBecause amines are a privileged functional group in bioactive molecules,1 the development of more versatile methods for their synthesis is an important objective.2 Whereas the alkylation of an amine by an alkyl halide via an SN2 pathway is a classic transformation, at the same time the process represents an ongoing challenge in synthesis.3 Thus, rather than the desired C\u2013N bond formation, undesired pathways such as E2 reactions and over-alkylation often intervene. Furthermore, because SN2 reactions are sensitive to steric effects, unactivated secondary and tertiary alkyl halides oftentimes do not serve as useful electrophilic partners. Due in part to these limitations, an array of methods other than the substitution reaction of an amine with an alkyl halide have been developed in order to selectively and efficiently introduce an alkyl group to an amine.2
Whereas transition-metal catalysis has been pursued very extensively to address the challenge of effecting substitution reactions of aryl halides by nitrogen nucleophiles,4 until recently there were essentially no systematic investigations of corresponding metal-catalyzed substitution reactions of alkyl halides.5 During the past few years, this deficiency has begun to be addressed, including through our work on photoinduced, copper-catalyzed processes (carbazoles, carboxamides, and indoles as nucleophiles)6,7 and a study by Hartwig on palladium-catalyzed reactions (benzophenone imines as nucleophiles).8
Nevertheless, to date a general method for transition-metal-catalyzed substitution of an alkyl halide by an aliphatic amine, which can be regarded as the prototypical nitrogen nucleophile, has not been described. In this study, we report a photoinduced, copper-catalyzed process that achieves the selective mono-alkylation of an array of aliphatic amines with unactivated secondary alkyl halides under mild conditions (\u221210 \u00b0C; eq 1).
In earlier work, we have described a variety of coupling reactions of nucleophiles with organic (aryl, alkenyl, alkynyl, and alkyl) electrophiles that are induced by light and catalyzed by copper;6,9 an outline of one of the possible pathways for such processes is provided in Figure 1.10,11 To date, all of our reported couplings have employed nucleophiles wherein the nucleophilic site is part of a \u03c0 system (N: carbazole, indole, and imidazole; S: aryl thiol; O: phenol; C: cyanide). On the other hand, our initial efforts to utilize nucleophiles that lack this feature were unsuccessful. For example, under conditions in which carbazole6a and cyclohexanecarboxamide6b undergo alkylation by an unactivated secondary halide in good yield, the corresponding alkylation of a primary aliphatic amine does not proceed (eq 2 and eq 3). Having the nucleophilic site incorporated within a \u03c0 system might be important for any of a variety of reasons, including determining the viability of the initial photoexcitation (A \u2192 B in Figure 1)12 and/or of electron transfer from that excited state to the electrophile to generate a copper(II) complex (B \u2192 C).13
\n \n \n \n
\n \n \n \n
\n \n \n \n
While examining the functional-group compatibility of a method that we had developed for photoinduced, copper-catalyzed arylations of phenols,9d we discovered that the presence of 1.0 equiv of an aliphatic amine additive unexpectedly leads to predominant N-arylation of the aliphatic amine, rather than O-arylation of the phenol (eq 4; in the absence of n-BuNH2: 80% yield of PhO\u2013Ar).
One of the possible pathways by which phenol might enable the photoinduced, copper-catalyzed cross-coupling of an aliphatic amine is depicted in Figure 2. Thus, photoexcitation of a copper(I)\u2013phenoxide complex (E \u2192 F) and then electron transfer to an electrophile (R\u2013X) affords a copper(II)\u2013phenoxide (G) and an organic radical (R\u2022). Ligand exchange of the copper(II)\u2013phenoxide with an amine (NH2R) leads to a copper(II)\u2013amido (H)14 that engages in C\u2013N bond formation with the organic radical to furnish the cross-coupling product (R\u2013NHR) and a copper(I) complex (I).15 Ligand substitution then regenerates a copper(I)\u2013phenoxide complex (E).
\n \n \n \n
Given the paucity of systematic studies of metal-catalyzed substitution reactions of unactivated alkyl halides by aliphatic amines, we attempted to exploit our initial observation (eq 4) to devise a photoinduced, copper-catalyzed process that would address this deficiency. Indeed, building on this lead result, we have been able to develop a method that achieves the selective mono-alkylation of a primary aliphatic amine by an unactivated secondary alkyl halide under mild conditions (\u221210 \u00b0C) in good yield (92%).
Control reactions establish that essentially none of the coupling product is generated in the absence of CuI, rac-BINOL, light, or BTPP (Table 1, entries 2\u20136). A variety of copper(I) and copper(II) sources furnish a good yield of the desired secondary amine, whereas copper nanopowder does not (entries 7\u201311). N-Alkylation proceeds less efficiently in the presence of less BINOL (entries 12 and 13) and when BINOL is replaced with related ligands (entries 14 and 15). The use of other Br\u00f8nsted bases (entries 16 and 17), a smaller excess of electrophile or BTPP (entries 18 and 19), or a lower catalyst loading (entry 20; no further reaction after 24 h) also leads to significantly lower yields. Under our standard conditions, other cyclohexyl electrophiles (bromide, chloride, and tosylate) do not serve as suitable coupling partners (entries 21\u201323). Cross-coupling does occur in the presence of a small amount of air or water, although less effectively (entries 24 and 25).
An array of unactivated secondary alkyl iodides, both cyclic and acyclic, serve as suitable electrophiles in this photoinduced, copper-catalyzed mono-alkylation of aliphatic amines (Table 2).16 The efficiency of the coupling is sensitive to steric effects, with more hindered electrophiles furnishing more modest yields (entries 6 and 7). Saturated oxygen and sulfur heterocycles are compatible with the reaction conditions (entries 8 and 9), and C\u2013N bond formation can be achieved with excellent diastereoselectivity (entries 11 and 12; >20:1). In a gram-scale reaction, the alkylation illustrated in entry 1 proceeds in good yield with 10% CuI/20% BINOL (1.32 g, 81%).
Although many unactivated primary alkyl halides can serve as useful electrophiles in SN2 reactions, neopentyl halides typically are rather poor substrates.17 Nevertheless, the combination of a CuI/BINOL catalyst and blue-LED irradiation enables the alkylation of an aliphatic amine by neopentyl iodide in good yield at \u221210 \u00b0C (eq 5). In contrast, a simple SN2 reaction proceeds very slowly even at 100 \u00b0C, and the addition of CuI/BINOL is not beneficial (eq 5).
\n \n \n \n
We have also examined the scope of this photoinduced, copper-catalyzed N-alkylation with respect to the nucleophile (Table 3). Thus, the efficiency of C\u2013N bond formation does not appear to be highly sensitive to the steric demand of the aliphatic amine (entries 1 and 2). The method is compatible with a variety of functional groups, including an ether, an acetal, an aryl chloride, an aryl bromide, a furan, and a thiophene (entries 3\u201310).
Through an additive study, we have further assessed the functional-group compatibility of this method. For the coupling illustrated in entry 1 of Table 2, the addition of 1.0 equiv of an alcohol (5-nonanol), an alkyne (5-decyne), an ester (methyl octanoate), a ketone (2-nonanone), a cis olefin (cis-5-decene), and a trans olefin (trans-5-decene) has little impact on N-alkylation (>75% yield), and the additive is virtually unaffected (>90% recovery). On the other hand, the addition of a nitroalkane (nitrocyclopentane) or an aldehyde (cyclohexanecarboxaldehyde) impede coupling (<5% and 51% yield, respectively).
If desired, N-protection of the secondary amine can be effected in situ in good yield. For example, upon completion of the alkylation illustrated in entry 1 of Table 2, direct trifluoroacetylation followed by purification provides the TFA-protected amine in 86% yield. Similarly, a 73% yield of the purified carbamate can be obtained after in situ protection with Boc2O.
Although reaction development is the primary focus of this investigation, we have also carried out preliminary mechanistic studies; as mentioned earlier, one of the possible pathways for this process is outlined in Figure 2. With regard to the identity of the primary photoreductant, ESI\u2013MS of a reaction mixture after partial conversion reveals the presence of copper(I)\u2013binaphtholate complex E'; alternatively, deprotonated BINOL itself could also fill this role.18,19 The illustrated mechanism includes d9 copper(II) complexes as intermediates, and we have indeed detected such species via EPR spectroscopy by sampling a catalyzed coupling at partial conversion; at least two copper(II) species are evident (hyperfine coupling to copper), which together account for ~60% of the total copper that is present in the reaction mixture.
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According to the pathway depicted in Figure 2, C\u2013N bond formation occurs through out-of-cage coupling of an organic radical (R\u2022) with a copper(II)\u2013amido complex.15 Consistent with this hypothesis, the addition of TEMPO (1.5 equiv) to a reaction mixture leads to the formation of a TEMPO adduct (eq 6).
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In summary, we have determined that the combination of visible light and a copper catalyst provides the first general method for the transition-metal-catalyzed alkylation of aliphatic amines by unactivated secondary alkyl halides. This process addresses some of the deficiencies of the classic SN2 approach, including its need for reactive electrophiles and its propensity for over-alkylation. With respect to our efforts to expand photoinduced, copper-catalyzed coupling reactions, this represents our first success with nucleophiles wherein the nucleophilic site is not part of a \u03c0 system. With our optimized method, C\u2013N bond formation proceeds without significant over-alkylation (<1%) under mild conditions (\u221210 \u00b0C) in the presence of a variety of functional groups, upon irradiation by blue-LED lamps of a catalyst derived from commercially available components. A preliminary mechanistic study is consistent with the formation of an alkyl radical that engages in out-of-cage C\u2013N bond formation. Our future work will focus on expanding photoinduced, copper-catalyzed couplings to other classes of non-conjugated nucleophiles, as well as on elucidating the mechanisms of these processes.
", "answer": "Although the alkylation of an amine by an alkyl halide serves as a \\xe2\\x80\\x9ctextbook example\\xe2\\x80\\x9d of a nucleophilic substitution reaction, the selective mono-alkylation of aliphatic amines by unactivated, hindered halides persists as a largely unsolved challenge in organic synthesis. We report herein that primary aliphatic amines can be cleanly mono-alkylated by unactivated secondary alkyl iodides in the presence of visible light and a copper catalyst. The method operates under mild conditions (\\xe2\\x88\\x9210 \\xc2\\xb0C), displays good functional-group compatibility, and employs commercially available catalyst components. A trapping experiment with TEMPO is consistent with C\\xe2\\x80\\x93N bond formation via an alkyl radical in an out-of-cage process.", "id": 269} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsince 1965 when brnemark et al.1 introduced and established the osseointegration concept , dental implant has achieved enormous development and progress . defined as direct connection between bone and implant surface ,\nosseointegration is formed by the process of bone formation between bone and implant surface . because the success and failure of implant is determined by osseointegration , it is a precondition for prosthetic repair through implant .\nthe primary stability is obtained by mechanical fixation of the implant with bone , and this is one of the basic conditions for osseointegration.2 primary stability is related with implant surface area , geometry , length , contact area between implant and bone .\nother factors include ratio of spongy bone vs. cortical bone , and implant technique.3 the secondary stability is generated secondarily by bone formation and bone remodeling in the process of osseointegration due to biological fixation in the interface between bone and implant.4 therefore , we can evaluate the degree of osseointegration through the measurement of changes in the implant stability.5 meredith et al .\nreported on the use of the resonance frequency analyzer to evaluate the stability of implant , and demonstrated the ability of the device to evaluate the changes in stiffness of the interface in the early in vitro experiment.6,7 recently , histomorphologic studies suggested that the resonance frequency value has a high correlation with the level of contact between bone and implant.8 - 11 this discovery supports the use of resonance frequency analysis to evaluate the changes in the process of osseointegration and bone healing after placement of implant .\nthe resonance frequency analyzer can measure clinically and noninvasively the stability of implant and estimate the degree of osseointegration . in this study , we used a recently developed magnetic resonance frequency analyzer to measure the stability of implant . for measurement unit , implant stability quotient ( isq ) is used which is recorded as a number between 1 and 100 with 100 representing the highest stability.12 this study intends to measure and analyze the changes in implant stability without load during an early healing period of six months after placement of three different types of implants by one stage implant . in this way , this study will provide useful information for prosthetic treatment planning through immediate and early loading after placement of implant as well as the evaluation of long - term prognosis for it .\na total of 28 patients ( 25 males and 3 females , mean age : 58.6 9.23 ) were selected among the patients who visited between march and september 2004 with the main purpose of implant placement .\ninclusion criteria were as follows \n adults aged 18 or olderpatients who understand and agree to this studyadequate oral hygiene ( 1 or lower mean modified sulcus bleeding index , 1 or lower mean modified plaque index)sufficient bone volume to place the planned implantone or more edentulous mandible parts which are six months or longer after dental extraction ( however , adjacent teeth must be healthy and properly repaired)fertile women who received pregnancy test no later than one week before surgery and have been confirmed to be negative \n adults aged 18 or older patients who understand and agree to this study adequate oral hygiene ( 1 or lower mean modified sulcus bleeding index , 1 or lower mean modified plaque index ) sufficient bone volume to place the planned implant one or more edentulous mandible parts which are six months or longer after dental extraction ( however , adjacent teeth must be healthy and properly repaired ) fertile women who received pregnancy test no later than one week before surgery and have been confirmed to be negative exclusion criteria were as follows \n smokers over 10 cigarettes / daya history of alcoholism or drug addition during the past 5 yearssevere teeth clenching or bruxismrisk of subacute bacterial endocarditisuncontrolled hypertension or diabetespatients with malignant tumor \n smokers over 10 cigarettes / day a history of alcoholism or drug addition during the past 5 years severe teeth clenching or bruxism risk of subacute bacterial endocarditis uncontrolled hypertension or diabetes patients with malignant tumor the three types of 45 implants were divided into 3 groups including osseospeed ( group a , astra tech , sweden ) , camlog ( group c , biotechnologies ag , switzerland ) , and replace ( group r , nobelbiocare , sweden ) in this study .\none assigned operator placed implants by one stage technique in accordance with the surgical protocol suggested by the manufacturer .\nbone quality classification followed the criteria proposed by lekholm & zarb , and type 1 , 2 , 3 or 4 was determined on the basis of the sense of resistance during bone drilling .\nafter placement , isq was measured , a healing abutment was connected , and sutured . for magnetic resonance frequency analyzer , this study used osstell ( gteborg , sweden ) .\na special smart peg was connected to the implant body at 4 - 5 n / cm torque , and measurements were made at 2 - 3 mm away so that the probe tip of the analyzer would point to the small magnet above the smart peg ( fig .\nif the probe measures two values simultaneously and the difference between these two values is 3 isq or higher , the values must be indicated simultaneously .\nisq was measured immediately after placement , after 3 weeks , 6 weeks , 8 weeks , 10 weeks , 12 weeks and 24 weeks .\nin addition , we examined the existence of discomfort at the time of healing abutment removal and the smart peg connection .\nthe data were analyzed by implant type , bone type , healing time , and location .\nthe data were recorded as implant isq over time , and were analyzed by implant type , bone type , healing time , and location . for the analysis by bone type , interaction between time and type with two - factor effect mixed model was used . here , the comparison between the time points used contrast comparison in the two - factor effect mixed model . for comparison of bone types at different time points , the multi - comparisons of anova and tukey were used ( p = .05 ) .\nthe analysis by mandible location used the time effect with two - factor effect mixed model and the location effect with two - factor effect mixed model .\nthe data were recorded as implant isq over time , and were analyzed by implant type , bone type , healing time , and location . for the analysis by bone type , interaction between time and type with two - factor effect mixed model was used . here , the comparison between the time points used contrast comparison in the two - factor effect mixed model . for comparison of bone types at different time points , the multi - comparisons of anova and tukey were used ( p = .05 ) .\nthe analysis by mandible location used the time effect with two - factor effect mixed model and the location effect with two - factor effect mixed model .\nthe surgeries produced no complications in all the patients and the isq numbers were obtained without causing inconvenience to the patients .\nbone types 2 and 3 were grouped together , because recent papers demonstrated that it was difficult to reliably differentiate the drilling resistance in intermediate bone .\nthe two - factor mixed model anova was used to determine the existence of interaction between bone type and time in groups a , c and r ( p = .0022 , p = .017 , p = .0018 ) .\nin other words , the change patterns of isq by time were different by bone type ( fig . 2 - 4 ) .\nfurthermore , the isq values of bone types were compared through multi - comparisons of anova and tukey . in the groups a , c and r , the measurements immediately after placement showed statistical differences in bone types 1 , bone types 2 & 3 , and bone type 4 ( p < .05 ) .\nthe mean isq of implants immediately after placement was over 70 in the bone type 1 , between 65 and 70 in the bone type 2 & 3 , and between 48 and 50 in the bone type 4 ( fig .\na , between week 0 and 6 , isq increased 4.78% in bone type 1 , 8.73% in bone type 2 & 3 , and 56.47% in bone type 4 .\nthe bone type 1 did not show significant change ( p = .052 ) , while bone types 2 , 3 and 4 showed significant changes ( p = .044 , p = .0326 ) . in group c , between week 0 and 6\n, isq increased 0.52% in bone type 1 , 6.38% in bone type 2 & 3 , and 49.11% in bone type 4 .\nthe bone type 1 , 2 & 3 showed slow increase between six weeks and six months .\nthe bone types 1 , 2 & 3 showed significant changes ( p = .0356 , p < .0001 ) , but type 4 did not show significant changes ( p = .3715 ) . in group r , between week 0 and 6 , isq increased 7.37% in bone type 1 , 11.87% in bone type 2 & 3 , and 47.81% in bone type 4 .\nthe bone types 1 did not show significant changes ( p = .6411 ) , but type 4 showed significant changes ( p = .0005 , p = .0462 ) . according to the two - factor mixed model , groups a and c did not show significant differences in stability changes by healing time according to the anatomical location between maxilla and mandible .\nin group r , the change of stability by healing time showed significant difference between maxilla and mandible ( p = .0238 ) .\nhowever , the comparison between maxilla and mandible by the two - sample t - test did not find significant difference among 3 groups ( fig . 9 - 12 ) .\naccording to the two - factor mixed model , groups a and c did not show significant differences in stability changes by healing time according to the anatomical location between maxilla and mandible .\nin group r , the change of stability by healing time showed significant difference between maxilla and mandible ( p = .0238 ) .\nhowever , the comparison between maxilla and mandible by the two - sample t - test did not find significant difference among 3 groups ( fig .\nthe need for clinical diagnosis tools with high accuracy to recognize the stability of implant and early healing changes is increasing along with the immediate and early load concept .\nthe resonance frequency device invented by meredith4 has been used for clinical reference of the stability of implant placed in various bone types .\nthere are several reports about implant stability influenced by healing time.8,10,11 this study also found through an analysis with the interaction between time and type with two - factor effect mixed model that the interaction of time and bone quality had significant influence on the isq values .\nthe result of implant stability immediately after placement was bone type 4 < type 2 & 3 < type 1 in all implant groups . the implant stability measured immediately after placement is primary stability resulting from the mechanical press - fitting of implant with a greater diameter than the hole in the bone , and is influenced by the stiffness of adjacent bones.3,4 in other words , the higher the stiffness of adjacent bones , the higher the primary stability .\ntherefore , the stability immediately after placement of bone type i that has a high volume of cortical bone and a small volume of spongy bone is higher . on the other hand , bone types 2 & 3 and type 4 have a less volume of cortical bone and a more volume of spongy bone , which decreases the stiffness of bones and lowers the stability immediately after placement of implant.13 the three bone types experienced great changes in stability between week 0 and week 6 . in an experiment with rabbits\n, robert14 reasoned that human bone quality would undergo significant changes between week 0 and week 6 by the formation of woven bone and the deposition of lamellar bone .\nfurthermore , the size of changes between week 0 and week 6 varied by bone type . the ascending order of the size of changes was bone type 1 > type 2 & 3 < type 4 .\nhowever , the cancellous healing showed was fast because in addition to trabecular remodeling , the bone is close to bone marrow that has a rich vascular system and mesenchymal progenitor cells which can be differentiated into osteoblasts .\ntherefore , it seems that the closer to bone type 4 , the higher implant stability by the fast regeneration of woven bones.15 the slow increase of implant stability between week 6 and six months ( plateau effect ) has been reported by cochran et al.16 this phenomenon has a correlation with the strengthened bone formation concept around the implant .\nrobert14 believed that the later stage of the deposition of the lamellar bone into the grids in human woven bones and the interface remodeling begins at week 6 and continues until week 18 , and the deposition of lamellar bone gives sufficient strength to withstand load .\nthe changes of stability by healing time according to the mandible location were not significantly different between the upper and lower mandible groups .\nthere are many existing studies that found that the lower mandible shows higher stability.17,18 the result of this study was different , which seems to be due to the small number of samples ( there were five cases of bone type 4 in the 13 maxilla cases )\n. the implant length may be an important factor that influences isq value.19 however , this study could not analyze the differences due to the insufficient number of samples by length .\nwithin the limitation of this study , we found that the time / bone quality interaction had significant influence on isq values through an analysis among implant groups a , c , and r. in other words , in all the implant groups a , c and r , the change patterns of isq over time differed by bone type .\nimplant stability increased greatly between week 0 and week 6 ( order of increase : type 1 < type 2 & 3 < type 4 ) , and showed slow increase between week six and six months ( plateau effect ) .\nhowever , no significant difference in stability changes by healing time according to locations was found in all the implant groups .\nmore studies are required about the mechanotransduction effect during the early implant loading in various implant systems , and the effect of this on the magnetic resonance frequency analyzer during the early healing period .", "answer": "purposeto determine the change in stability of single - stage , three different design of implant systems in humans utilizing resonance frequency analysis for early healing period ( 24 weeks ) , without loading.material and methodstwenty - five patients were included into this study . a total of 45 implants , three different design of implant systems ( group a , c , r ) were placed in the posterior maxilla or mandible . \n the specific transducer for each implant system was used . \n isq ( implant stability quotient ) reading were obtained for each implant at the time of surgery , 3 , 6 , 8 , 10 , 12 , 24 weeks postoperatively . \n data were analyzed for different implant type , bone type , healing time , anatomical locations.resultsfor each implant system , a two - factor mixed - model anova demonstrated that a significant effect on isq values ( group a = 0.0022 , c = 0.017 , r = 0.0018 ) . \n for each implant system , in a two - factor mixed model anova , and two - sample t - test , the main effect of jaw position ( p > .005 ) on isq values were not significant.conclusionsall the implant groups a , c and r , the change patterns of isq over time differed by bone type . \n implant stability increased greatly between week 0 and week six and showed slow increase between week six and six months ( plateau effect ) .", "id": 270} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 50-year - old , 168 cm , 68 kg man without significant past medical history , was admitted to emergency room following a slip - down accident . on admission ,\nneurologic examination confirmed a glasgow coma scale ( gcs ) of 15 , and the pupils were symmetrical and reactive . emergent skull x - ray series , facial computerized tomography ( ct ) and forearm x - ray revealed fracture of the frontal sinus , skull base , and right distal radius fracture . computed tomography ( ct ) of the brain showed multiple small subdural pneumocephalus ( fig .\nemergent lumbar drainage was performed to manage csf rhinorrhea and empirical prophylactic antibiotic treatment was given .\nthe patient 's post - traumatic symptoms improved gradually in the surgical intensive care unit . at post - trauma 8 days , following trauma , the patient underwent orthopedic surgery for distal radius fracture under general anesthesia .\nanesthesia was induced with intravenous thiopental 300 mg and 0.5 g / kg / min remifentanil infusion .\nendotracheal intubation was performed after administering 50 mg rocuronium injection with 100% oxygen mask ventilation for 3 min without any difficulties .\nanesthesia was maintained with oxygen ( 2 l / min)-air ( 2 l / min)-sevoflurane ( 1 - 1.5 vol% ) , continuous infusion of 0.125 - 0.5 g / kg / min remifentanil and 10 - 15 mg / h of rocuronium .\ntidal volume and respiratory rate were adjusted to maintain end - tidal carbon dioxide tension at 30 - 35 mmhg .\nfollowing surgery , the patient was extubated in the operation room after gaining consciousness and spontaneous ventilation .\nhe was then transferred to the post - anesthesia care unit where he recovered fully without complications .\nten hours later , the patient complained of severe , increasing , headache and exhibited abrupt deterioration in mental state . in view of his clinical aggravation ,\nneurologic examination demonstrated a gcs 11 and emergent brain ct showed large quantity of both frontal and right occipital pneumocephalus ( fig .\nhigh flow ( 8 l / min ) oxygen via a partial non - rebreathing mask was administered in conjunction with supportive care for 2 days .\nno infectious neuromeningeal complications occurred during hospitalization , and the patient was discharged at post - trauma day 32 .\nit develops mostly from acute and subacute complications of head trauma , or as late complications during the recovery phase of head injury .\nsubarachnoid or subdural air accumulation is the most common form of pneumocephalus , and intracerebral pneumocephalus can occur albeit rarely .\nintracranial air is accumulated as a result of communications between paranasal sinuses , mastoid air cells and the cranial fossa , associated with dural tear .\nthe other mechanism of air penetration is a ball - valve effect like sudden increase of nasopharyngeal pressure , such as during coughing and sneezing , forcing air into the cranial cavity which subsequently remained trapped .\ninjuries of the paranasal sinuses , which are closely contiguous to bony structures , the dura mater and the brain frequently accompany head traumas .\n75 - 90% of pneumocephalus are posttraumatic and the incidence of pneumocephalus secondary to head injury range from 0.5% to 13.2% .\nother causes include facial tumors that eroded through the skull , gas - forming bacterial infections , paranasal sinusitis and neurosurgical and facial procedures .\npneumocephalus is mostly asymptomatic and self - limiting , because gas is not irritating to the surrounding brain .\nintracerebral pneumocephalus have usually become sizable when it is confirmed by simple skull x - ray or brain ct .\ntension pneumocephalus caused by large amounts air can evoke sudden or insidious mass effects capable of shifting midline structures , causing major neurological deficits .\nrepresentable iatrogenic pneumocephalus are related to positive pressure ventilation in the upper airway , such as nasal continuous positive airway pressure , face mask ventilation and even nasal oxygen cannulae .\nit is well known that positive airway pressure can result in pneumothorax , pneumomediastinum and subcutaneous emphysema .\nit is difficult to predict which head trauma patients who do not initially develop pneumocephalus will experience iatrogenic pnemocephalus during positive pressure oxygen therapies .\nthe mechanism of air delivered via manually operated mask tracking into the cranial cavities appears to be identical to that in traumatic pneumocephalus . because csf leakage is usually a result of osteomeningeal fistula , csf rhinorrhea is commonly associated with pneumocephaus , as demonstrated in this patient .\nhis initial primary pneumocephalus accompanied by rhinorrhea was completely subsided following lumbar drainage and general supportive care , but post - anesthetic secondary pneumocephalus probably developed during anesthesia induction using ppmv .\ntherefore , avoidance of excessive positive pressure during mask ventilation is recommended to prevent pneumocephalus . because most mild pneumocephalus usually recover spontaneously within one week\n, its management includes strict bed rest in the semi - fowler position , analgesia and antibiotics .\nprevention of intracranial pressure elevation by avoiding the valsalva maneuvers , coughing , sneezing , nose blowing , and excessive physical activities is important to avoid pneumocephalus aggravation . because severe headache , personality change , disorientation , and mass effect associated with midline structure shift are the symptoms and signs of tension pneumocephalus , emergent surgical procedures , such as subdural drainage to decrease intracranial pressure , should be considered immediately after confirming the diagnosis with x - rays or brain ct .\nwhen the patient experienced severe headache and became rapidly lethargic , analgesia , antibiotic and high flow , high fio2 oxygen via a partial non - rebreathing reservoired mask were administered under a presumed diagnosis of impending tension pneumocephalus .\nthe management principle is as follows : high fio2 oxygen reduces blood and brain tissue nitrogen concentration , thereby increases the nitrogen concentration gradient that promotes pneumocephalus gas absorption . to avoid tension pneumocephalus in head trauma patients , lma or tracheostomy tube intubation\nin addition , anesthesiologists should be aware of potential complications caused by low intracranial pressure during anesthesia in head trauma patients . in theory ,\nhypotension , hypovolemia , excessive hypercapnia and head - up position during anesthesia can reduce intracranial pressure that facilitates air influx through open osteomeningeal fistulae secondary to head trauma , causing pneumocephalus . in conclusion\n, anesthesiologists and surgeons should be aware of pneumocephalus as a potential complication during positive pressure mask ventilation for facial trauma , secondary to air invasion through osteomeningeal fistulae .\nclose monitoring for pneumocephalus development should be mandatory following general anesthesia or during respiratory care with continuous positive airway pressure in head trauma patients .", "answer": "pneumocephalus is a condition which usually results from head trauma . \n it has been known that iatrogenic pneumocephalus can occur as a complication of positive pressure mask ventilation during induction of anesthesia or ventilatory care for head trauma patients . \n we report a case of mask ventilation during anesthesia induction in a 50-year - old male patient with head trauma . \n initial pneumocephalus associated with cerebrospinal fluid leakage was diagnosed immediate following head injury involving facial sinuses . \n he was managed with emergent lumbar drainage and supportive care . \n pneumocephalus recurred following positive pressure mask ventilation ( ppmv ) during anesthesia induction for surgery on the right arm . \n recurred pneumocephalus was managed with high flow oxygen and supportive care . \n anesthesiologists should be aware of pneumocephalus as a potential complication of ppmv in head trauma patients , even after resolution of previous pneumocephalus .", "id": 271} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noculogyric crisis ( ogc ) , classified as eyeball dystonia , was first described in patients suffering from encephalitis lethargica.1 nowadays , this symptom is more frequently observed as a side effect of treatment with dopamine receptor - blocking drugs ( drbds).2 it manifests as spasmodic deviations of the eyeballs , mainly upward but also in other directions , lasting from a few minutes to several hours.3 it occurs during the first hours or days after the introduction of drbds .\ntetrabenazine is mainly used in patients with hyperkinetic movement disorders , such as tics , chorea , tardive dyskinesia , and dystonia .\nits mechanism of action involves the reversible inhibition of vesicular monoamine transporter type 2 , thus preventing the uptake of serotonin , norepinephrine , and dopamine by presynaptic neurons .\njankovic and beach found that acute dystonic reactions occurred in nine ( 2.3% ) patients and two ( 0.5% ) additional patients had acute oculogyric crises attributed to tetrabenazine.4 we present a case report of a patient suffering from gilles de la tourette syndrome ( gts ) who developed ogc during treatment with tetrabenazine .\nan 18-year - old male patient with gts began to experience head shaking followed by coughing at the age of 11 years . during the next several years , he developed numerous motor and vocal tics ( nose twitching , jaw tightening , biting his cheek , clenching his fingers into a fist , throwing his head back , rolling his eyes to one side , tensing his buttocks , twisting movements of the hands and feet , resulting in abnormal posture , bending his body to one side giving the sustained position of his body , and exhaling loudly ) .\nhis tic - reducing therapy included haloperidol , perphenazine , quetiapine , sulpiride , and clonazepam without success , and thus he was referred to piotr janik ( the first author of this paper ) at age 17 years .\nhe had a positive family history of tics ( his brother ) and obsessive compulsive behaviors on his paternal side ( his brother , uncle , and grandfather ) .\nwe found his tics to be associated with lower educational achievements and negative impacts on his family and social life . during the next year\n, he was put one by one on risperidone , aripiprazole , and topiramate without success . during another visit at age 18 years , he presented with jaw snaps , head jerks , quickly flexing and extending arms , popping knuckles , tensing of the abdomen , nose picking , rubbing one foot against the other , bending up of the nose using a finger combined with frowning , and rapid jerking of the body .\nhis vocal tics included screeching ; throat clearing ; and sniffing , humming , and squeaking noises .\nhe also displayed self - injurious behavior he had to use a mouthguard to protect his teeth from damage caused by clenching his jaw . to assess the severity of his tics\ncomorbid conditions included depression at age 16 treated with escitalopram and paroxetine . at the time of examination ,\nno comorbid mental disorders were diagnosed . due to the lack of effectiveness of previous treatments , tetrabenazine in gradually increasing dose\nwas introduced . however , after 8 days of therapy , at a dose of 62.5 mg of tetrabenazine daily , the patient developed involuntary movements of the eyeballs characterized by spasmodic deviations of the eyes upward and to one side that lasted for around an hour , with a frequency of a few times per day .\nin addition to ogc , the patient experienced severe , brief episodes of throwing back his head and twisting movements of his hands and feet that resembled retrocollis and limb dystonia , respectively .\nexcessive salivation , slurred speech , and food dropping from the mouth were also reported by the patient .\nall symptoms resolved a week after tapering the tetrabenazine dose to 37.5 mg daily . at this dose , tics remained poorly controlled and tetrabenazine was totally stopped . despite further treatment with other drbds , among them\npermission from an ethics committee was not necessary in the presented case , as tetrabenazine is a widely approved treatment for gts .\nthe drug has previously been used as a last - resort treatment for patients with severe tics ; therefore , no novel medical treatments were performed on our patient .\nacute ogc seems to be a rare complication in the treatment of gts patients because , nowadays , mostly second - generation drbds are used to alleviate tics .\nthere are only a few case reports in the literature of this complication arising with the use of second - generation drbds .\ntwo papers report the development of acute ogc shortly after administration of aripiprazole and one paper reports similar symptoms after treatment with risperidone.57 we also observed two young adults with gts who developed ogc after treatment with risperidone 4 mg daily and sulpiride 300 mg daily .\nthe only two reports of tetrabenazine - induced acute dystonia were those of jankovic and beach4 and burke et al.8 the four patients described by burke et al varied in terms of drug dose ( from 25 to 300 mg ) , underlying condition ( gts in one case , dystonia in three others ) , patients age ( from 20 to 30 years ) , and sex ( two females , two males).8 unfortunately , the characteristics of patients who developed acute dystonia with tetrabenazine treatment were not included in the second paper.4 both authors reported that acute dystonia was dose - related and improved spontaneously when the dosage was reduced , as was the case with our patient . in contrast to burke s patient with gts who developed ogc and retrocollis while being treated with tetrabenazine 300 mg , we observed such a complication on a low dose of tetrabenazine .\nthe fact that tetrabenazine - induced ogc is rarely seen and may occur with different doses suggests that this complication will develop in vulnerable young adults in particular .\nin addition , our patient had some dystonic tics as part of his tic repertoire since early adolescence .\ninterestingly , these tics as well as some facial and cervical motor tics worsened during treatment with tetrabenazine .\nthe severity of all these tics abated after tetrabenazine treatment was reduced and then stopped . since dystonic tics often resemble acute dystonic reaction , it is not always easy to differentiate these movement disorders . compared to dystonia , tics are shorter lasting movements , typically not painful , are preceded by premonitory sensations , and do not cause persistent postures .\nbased on these clues , we classified these movements as worsened tics rather than drug - induced acute dystonic reaction .\nit is believed that to cause acute dystonic reactions , the drug must be able to block dopamine receptors .\nhowever , tetrabenazine , a monoamine - depleting medication , and alpha - methyl - para - tyrosine , a catecholamine - depleting agent , may induce acute dystonic reactions.8,9 our case report is not in line with the hypothesis that tetrabenazine causes this side effect by dopamine blockade rather than monoamine depletion because it is also able to block dopamine receptors in rat brain.10,11 our patient had been exposed to numerous drbds before and after he developed ogc , which never caused symptoms of acute dystonia .\nthe resolution of ogc after a reduction in the dosage of tetrabenazine , which probably resulted in enhanced dopaminergic transmission , is compatible with the theory that the decrease of dopamine transmission induced by tetrabenazine could also be involved in the pathogenesis of acute dystonia .", "answer": "tetrabenazine is used in the treatment of chorea , tardive dyskinesia , tics , and dystonia . \n it rarely causes acute eyeball dystonia and the description of this complication in gilles de la tourette syndrome is limited . \n we provide a description of an acute oculogyric crisis caused by tetrabenazine in a patient with severe tics . \n the patient had never developed acute dystonic reactions , although he was previously exposed to numerous dopamine receptor - blocking agents . \n after 8 days of therapy with tetrabenazine at a dose of 62.5 mg daily , the patient developed involuntary movement of the eyeballs . \n withdrawal of tetrabenazine caused resolution of all symptoms after a week . \n the purpose of this description is to draw attention to the potential of tetrabenazine to induce acute oculogyric crisis as well as the difficulty of differentiating drug - induced dystonia from dystonic tics in patients with gilles de la tourette syndrome .", "id": 272} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npursuing the goal of improved health literacy requires more alliances between health and education sectors to improve literacy levels in the population .\nit is important for health educators to know about knowledge transfer to meet their needs in transferring their knowledge to public\n. knowledge transfer , which means the synthesis , exchange and ethically application of knowledge within a complex system of relationship among researchers and users , has become one of the recent priorities in research centers . the word \nthe method of knowledge transfer , apart from its characteristics , requires active interactions between researchers and users .\ncaplan proposes the two- communities theory indicating a gap between researchers and policymakers , whereas these days another gap has been formed between researchers and other users .\nin addition to illiteracy in developing countries that hampers effective health education , there are multitudes of non - medical specialists who do not have enough information about daily health affairs , and this lack is more remarkable in countries that welcome immigrants .\nimmigrants often have significant language and health literacy difficulties , which are further exacerbated by cultural barriers .\nalongside with sophisticated methods like computer and internet , using simple methods help us bring to achieve our health goals[68 ] . also , the lack of health literacy needs more attention when it is manifested in caregivers .\nit is believed that some of the undesirable health outcomes in children are because of inadequate health knowledge among caregivers . in the usa ,\ntherefore researchers have considered different methods to come up with this deficiency by having children to cooperate in their health programs .\na research group in india endeavored to transfer knowledge on leprosy in cooperation with children and informed their parents through them .\njacob et al ( 1994 ) started conducting a similar research that yields promising results .\nrimal and flora ( 1998 ) express that parental dietary behavior is partially affected by children .\nthe findings from studies in this field have encouraged other experts to apply similar methods to conduct their research projects , allahverdipour and bashirian , onyango - ouma and mwangagain from the influence of children in order to teach different parts of their society[1316 ] . despite the researcher 's trends in using novel methods in this field ,\nnone of them have used childish poem as a medium for knowledge transferring . in this study\n, we try to raise families health knowledge about infectious diseases by a method that uses children as health agents .\ninfectious diseases are still the leading cause of mortality in children less than 60 months in developing countries .\njuvenile age is accompanied by learning childish poems , which can be sung contnuously at home and potentially become as part of both children 's and parents memories .\nwe decided to transfer health knowledge to families through altering this information to childish poems and teaching children at kindergartens . in this method\nthe outcome of transferring health knowledge through childish poems has been assessed in this study .\nin this study , we use the method of interventional pre and post series to conduct our research .\nthe proposal of this non - invasive project was approved by the research committee of hamadan medical university in january 2009 .\nit was also accepted by hamadan welfare organization , which is the responsible organization of kindergartens in hamadan .\nour methodology is briefly explained as follows . at first , a sub specialist in pediatric infectious diseases provides seven short texts about health and common pediatric infectious diseases prevention .\nthen , a poet transfers these conceptions to childish poems for the first time ( appendix 1&2 ) . in the process of preparing an accurate questionnaire , at first 30 questions with three choices of \n, false and do not know were made , but 24 items of those are confirmed as valid questions by two experts of health education and infectious diseases . to assess\nthe reliability of the questionnaire a pilot study on a 40 participant sample was performed and cronbach 's alpha of the questionnaire was determined as 83 percent .\nin addition , we defined knowledge mark ( km ) as a parent mark in both the pre - test and/or post - tests . among 35 kindergartens in hamadan , we selected 7 kindergartens by simple random method .\nthe parents ( either father or mother , the one who is responsible to take her / his child ) of all five to six year old children of the selected kindergartens are asked to participate in the survey and a verbal consent is obtained from those who accepted .\nwe excluded the following children from our sample : those whose parents are physicians , nurses , health - care workers , and those children whose parents work at the kindergarten ( exclusion criteria ) .\nwe asked the parents of the sample survey to participate in a pretest by answering to a questionnaire when they are in the kindergartens .\nalso , they were asked to come to the kindergartens personally one more time when it is required ( to answer to the post test ) . then , we asked our kindergarten tutors to teach children seven musical poems about hydatid cyst , antibiotic misuse , botulinum toxin in home - canned foods , dysentery , the importance of sixth tooth , brucellosis and tetanus . in this step , children were not allowed to take home these texts , but they were asked to sing the poems at home and want their parents to re - write the poems on a paper and give them the papers to take to the kindergarten .\nthe teaching stage took between three to four months . during the next stage , parents took a post - test survey with the same 24 questions .\nparents of 115 kids participated in the pre - test and 103 of them completed the post - test .\nstatistical analysis is done on 103 who completed both tests by paired t - test .\nthe sample data consists of 103 parents who provided solutions to both the pre- and post - test question survey . of the participants 77 were female and 26 male . from the level of education point of view\n, 19 were below high school diploma , 45 had high school diploma , 8 had associate degree , 27 had ba , 3 had ma , and 1 had phd .\nthe results of the survey show a significant difference between the correct answers in both pre - test and post - test stages ( fig .\n1 ) . the frequency of correct answers to the tests \n table 1 shows the mean of the correct answers in the pre - test stage is 59.22 while the same figure for the post - test step is 81 ( p < 0.001 ) .\nin addition , we define knowledge mark ( km ) as a parent mark in both the pre - test and/or post - test stages . the mean km shows a significant increase ( 5.01 ) from 13.62 in the pre - test to 18.63 in the post - test ( table 2 ) . \n \nmean percent of correct answers to pre - test and post - test categories \n analyzed by paired t - test sd : standard deviation mean of knowledge mark in pre - test and post test analysed by paired t - test the difference of km promotion among females and males was not significant ( 21.6120.17 in males and 20.331.61 in females , p=0.8 ) . the km was increased to 19.9325.06 among parents who at most had high school diploma and 23.4720.84 among parents with upper educational levels ( p=0.5 ) .\nhealth has been the concern of poets such as fiona sampson for years , however , these poems never had educational purposes . the results of this study\nconfirm our hypothesis about the role of children in raising family 's knowledge on health .\nthe results show that neither gender nor the grade of knowledge degree ( below and upper high school diploma or below and upper ba ) affect answers .\ntherefore , people with different educational status have received the information similarly implying that this method can be extended to general cases in a straightforward manner . \n\n1 shows that the percentage of correct answers has increased in 23 out of 24 questions .\nthe percent - age of correct answer to post - test has decreased only in one item ( item 11 ) which compares the risk of brucellosis transmission via unpasteurized milk and yogurt . although the term yogurt has not been mentioned directly in the related poem , but there is a hint about boiling mechanism and we expect that the audience discover the answer by logical thinking about the necessitation of boiling milk for preparing yogurt .\nthe decrease in answering is 2 percent which is not significant ; however , it shows that it would be better to mention the conceptions directly in these types of poems in order to avoid any misconceptions .\nmoreover , the percentage of correct answers to the questions of selected topics in pre - test and post - test has been compared ( table 1 ) and shows that parents have done better in post - test about all topics except one .\nthe difference of correct answers to the questions about brucellosis does not show a significant increase in post - test .\nthis finding is probably due to higher basic knowledge about brucellosis among parents . in other words , parents have had acceptable information about brucellosis even without our educational program , so we observe lower contrast between pre - test and post - test about brucellosis\n. it should be taken into consideration that brucellosis is an endemic disease in hamadan and people have been educated in different ways about this disease in recent years . although the lowest contrast between pre - test and post - test correct answers belongs to a question about botulism , the overall assessment shows that parent 's knowledge about this topic has been promoted significantly ( p<0.001 , table 1 ) . the significant difference between the pre - test and post - test km , based on the results of table 2 , is the sign of successful knowledge transfer through childish poems .\nthe researcher 's method is impressively successful ; however , the fact that he mentions that some mothers can not distinguish the semantic difference between information and advice , needs serious attention .\nin addition , since daughters may misunderstand the information , it would be probable to transfer the misconceived information to their mothers and this fact threats the successfulness of study in applying . while , in our study ; firstly , childish poems do not imply sententious , secondly , if the poem is sung wrong , the disturbance in rhythm will be appeared , so the information which is transferred through poems is not at risk of alteration . in evans research ,\nparents get familiar with educated topics with the help of their children in homework assignments designed for asthma management , and are taught about asthma indirectly .\nthe advantage of our study in comparison with evans is that in evans method knowledge transfer brings to bear via homework assignment , while in our study there is no obligation for doing home works , and parents are educated while enjoying their child 's singing . on account of the fact that making communication with younger children is not as difficult as with adolescents for parents , we are sure that knowledge transfers within a family through a continuous and friendly communication will work .\nchristensen expressed the importance of children 's role in promoting the family health status . in his article , he emphasized on the activities that children can perform to enhance their health and promote their family health situation via the health efforts for themselves .\nwe showed that children , additionally to what christensen mentioned , are able to affect their family 's health status directly . they can improve their family 's health as little teachers in health .\nit should be taken into consideration that the limitations of this study was the impact of other media on participant 's knowledge , which was not preventable .\none of the acceptable results of this survey was publishing the poems as a book for children which was republished and welcomed by public .\nthis study 's results suggest that health knowledge transfer to families through childish poems is an applicable method that has many advantages . by applying this joyful , cost - effective and easy - to - use method\nhowever , it should be taken into consideration that this method is applicable for families with trainable children , for teaching in larger scales more general ways should be added to this method .\nmoreover , the simplicity of poems and expressing the topics in a less elaborative form are the key factors that affect the successfulness of this way .", "answer": "objectivethe purpose of this study is to propose an innovative method of knowledge transfer that aims to improve health literacy about pediatric infectious diseases prevention in families . \n children have an appreciable role in this scheme.methodsthis study is a before and after trial that has been conducted in hamedan in 2009 . after changing seven infectious disease topics into childish poems , we selected five kindergartens randomly and taught these poetries to the children . teaching process held after a pretest containing 24 questions that examined 103 of parents about mentioned topics . \n the same post - test was given after 4 months of teaching process.findingsthe mean of correct answers to the pretest was 59.22% comparable with 81.00% for post - test ( p<0.00 ) . \n gender and knowledge degree could not change the results significantly . \n assuming one 's correct answers to the questions as his / her knowledge mark , the mean of this variable increased to 5.32 by this method.conclusionthis cost - effective and joyful method had successful results in promoting health knowledge . \n children are able to play an active role in family 's health situation . \n learning within family atmosphere without any obligations makes our scheme a solution for paving the knowledge transferring way .", "id": 273} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe class i elements include the long terminal repeat ( ltr ) retrotransposons , the non - ltr retrotransposons and the short interspersed nucleotide elements ( sines ) 1 , 2 .\nthe class ii elements have terminal inverted repeats with transposase - binding sites , and include the p elements found in drosophila .\nthe best - known sines are the alu elements of primates , which are thought to have a common origin with the b1 elements of rodents 1 , 3 , 4 .\nalu elements are the most abundant transposable elements in the human genome , being present in about 500,000 copies .\nthese retroposons consist of two related monomers in tandem and , as the name implies , contain a restriction site for the enzyme alui .\nthey have no open reading frames , and the factors necessary for their amplification are thought to come from long interspersed elements ( lines ) which code for functional reverse transcriptases with an endonuclease domain 2 , 4 .\nthe present work describes the first sine detected in the genome of the cephalochordate amphioxus .\nprevious studies of transposable elements in amphioxus are limited to a class i non - ltr retrotransposon ( bfcr1 ) 5 and a class ii , non autonomous transposable element ( ate-1 ) 6 .\namphioxus ( branchiostoma ) is an aquatic invertebrate with a much simpler body plan than vertebrates ( e.g. no paired eyes , ears or limbs ) .\nmoreover , the amphioxus genome appears to have a similar organization as that of vertebrates but lacks the extensive gene duplications that occurred in the vertebrate lineage 7 .\nhowever , recent analyses done with large gene sets have placed amphioxus basal in the chordates with the rapidly evolving tunicates as the sister group of vertebrates 8 , 9 .\namphioxus is , therefore , the most appropriate organism for comparison with vertebrates to understand how the vertebrates evolved from invertebrate chordate ancestors .\nthe surprising finding of the present work is not that amphioxus has transposable elements or that this element is a sine , which are common in eukaryotic genomes , but that it contains three alui sites , two of which are in tandem .\nthus , the finding of an alu element in amphioxus raises the question whether amphioxus and primates are an example of convergent evolution or whether they both arose from an alu element in the ancestral chordate .\nthe transposable element was located by blastn searches of the amphioxus ( branchiostoma floridae ) genome sequences in the trace archives of genbank with portions of the upstream regulatory region of the foxd gene ( af512537 ) , which we had sequenced from cosmid mpmgc117o0129 available from the rzpd ( http://www.rzpd.de ) .\nsequences that were present in this cosmid , but absent from at least one of the foxd alleles in the trace archives , were suspected transposable elements . additional copies of this transposable element were located by blastn searches of amphioxus bac clones deposited in genbank .\nwe have previously identified a notochord - specific enhancer in the foxd gene in amphioxus ( branchiostoma floridae ) 10 .\nthis enhancer encompassed 4.7 kb upstream of the atg start codon and has several binding sites for the notochord marker brachyury as well as for fox d itself , suggesting autoregulation .\nsubsequently , we determined that the 5 ' portion of this enhancer , which includes these binding sites , is essential for directing expression to the notochord [ j - k .\n] however , just downstream of the foxd binding sites are two sites for foxa2 ( hnf3 ) , which , like brachyury , is expressed in the notochord ( figure 1a ) .\ntherefore , it seemed likely that this region with the foxa2 sites is also involved in directing notochordal expression .\nsurprisingly , blast searches of the amphioxus genome sequences in the trace archives of genbank , which represent the two alleles of a single individual , revealed that both alleles lacked the region with the foxa2 binding sites that corresponds to 1168 to 1543 upstream of the foxd atg start codon in the clone we previously sequenced , which was from a different individual ( figure 2 ) .\nmoreover , we found this 375 bp region in numerous traces with flanking regions that did not correspond to the foxd gene .\nan estimate would be 50 - 100 copies in the genome of the individual sequenced .\nfigure 1b compares this sine with eight representative homologous sines found in the trace archives and in cosmid sequences , all of which are from the two alleles of the same individual .\nthe first two of these eight sines are located in cosmids containing respectively , the tbx15/18/21 gene and the pax1/9 gene . in the former ,\nthe sine is 4200 bp upstream of the atg start codon of tbx15/18/21 and in the latter it is 40 kb upstream of the 5 ' end of pax 1/9 and located within an intron of a hypothetical gene coding for a cyclic nucleotide - gated cation channel .\nthe remaining sines in figure 1 were contained in relatively short bac end sequences and genomic traces , and therefore , their location relative to particular genes can not be determined until the full genome sequence is available .\nthe amphioxus sine has several characteristic features of sines in general and of primate alu elements in particular , and i , therefore , term it the amphi - alu element .\nsines generally are about 300 bp long with a polya tail of varying length and have similar , but not identical , left and right halves 11 - 13 .\nsines typically have a region derived from trna that contains a consensus rna polymerase promoter 14 .\nthe amphioxus element is 375 bp long , the polya tail ranges from 1 - 13 bases ( figure 1b ) , and the right and left halves are 52% identical ( clustal w alignment ) .\nmost of the copies of this element have from one to three alui sites , although they can be mutated ( figure 1b ) .\nmoreover , alignments with trna sequences from sea urchin available at http://lowelab.ucsc.edu/gtrnadb/ reveal a high percentage of identities with a sea urchin trna for glutamine with an imperfect match for the rna polymerase promoter a site and a nearly perfect one for the b site ( figure 3 ) . as is typical for sines , deletions of portions of either the left arm or the right arm are common .\nshow that these repeats are within the alu element and not in the flanking region .\nsuch repeats are lacking at the 3 ' end of the alu element and in the adjacent 3 ' flanking sequence .\nfigure 2 shows the insertion site in the foxd gene for an allele lacking amphi - alu .\nthe potential insertion site in is between 2 t residues and is flanked by direct repeats of ctttgtt . in the clones containing the amphi - alu element , there are direct repeats in the flanking regions of some clones ( e.g. gttttattg / gtttcttg for foxd ) .\nhowever , direct repeats are not always present on either side of amphi - alu , raising the possibility , which can be tested when the full genome assembly is available , that some amphi - alu sines may be longer than the one in the amphifoxd allele shown in figure 1 10 .\none unusual feature of amphi - alu is that the region with the highest identity to a trna is from base 199 to base 183 , rather than at the 5 ' end 13 as is typical for sines .\nalthough it is possible that figure 1 depicts amphi - alu in the reverse orientation , this is not likely since a varying number of a residues were present in all clones at the end designated as the 3 ' end in figure1b .\nmoreover , comparisons of the reverse strand of amphi - alu with trnas from a range of species , including sea urchin , had few matches .\nthis raises the possibility that the amphi - alu sine is a chimeric element , but it is puzzling that in either orientation , the putative rna polymerase iii sites are not near the ends of the element .\nalu elements have previously been described only in primates 15 , raising the question of whether amphi - alu and primate alu elements are descended from a common ancestral alu , or whether the presence of alu sites in these two sines from primates and amphioxus represent convergent evolution .\nit has been argued that the fla ( free left arm ) alu family arose at the origin of mammals about 112 mya 15 .\nhowever , alignments of human alu elements and amphi - alu do not reveal a high level of identity ; in general , amphi - alu is not as gc rich as human alu elements , and the most at - rich region is not central as in human alu elements but starts at base 290 .\nmorover , human alus and the related b1 elements of rodents have a 7sl rna - related region 3 , 13 , 16 , while amphi - alu is related to a trna for asparagine .\nthus , since amphioxus and vertebrate lineages are estimated to have split about 520 mya , it seems more likely that the alu sites in the amphioxus and mammalian alu elements have arisen through convergent evolution . however , there are few descriptions transposable elements in basal vertebrates such as agnathans 17 or in tunicates 18 , which recent phylogenetic analyses place as the sister group to vertebrates , amphioxus being basal in the chordates 8 , 9\n. alignments of a tunicate sine ( cics-1 ) , which lacks alui sites , with amphi - alu reveal only a few short regions of identity 18 .\na thorough study of transposable elements in amphioxus and these animals is critical for understanding the evolutionary history of alu elements . in the three instances where complete cosmid or bac sequences were available ,\nthe amphi - alu elements were located in likely regulatory dna either upstream of the atg start codon ( foxd and clone ch302 63l21 ) or within an intron ( ch302 119j21 ) .\nhuman alu elements within introns have been implicated in alternative splicing and exonization whereby part of the sine is not spliced out of the mrna and can cause frame shifts and gene inactivation 2 , 19 .\nmoreover , whether in the upstream regulatory region or in an intron , sines may provide binding sites for transcription factors and thus influence gene regulation .\nthe amphi - alu element has probable binding sites for foxa2 , which is normally expressed in the endoderm and notochord of amphioxus 20 .\nits location in the foxd gene just downstream of an important enhancer ( figure 1a ) , suggests that it might be contributing to regulation of the foxd gene in the individuals that have it in the foxd regulatory region .\nalu elements have been implicated in regulation of many genes 21 , 22 . to what extent\nsuch transposable elements might mediate evolution of cis - regulation in animals in nature is not known .\nhowever , it is certainly a possible mechanism for effecting large changes in cis - regulation . in summary ,\nthe finding of an alu element in the amphioxus genome that is present in the regulatory dna of some , but not all , alleles of the foxd gene and in the regulatory regions of other genes raises questions both about the evolution of sines in chordates and suggests that the insertion of such sines into regulatory dna could mediate evolution of cis - regulatory regions .\nthere is some evidence for positive selection for such transposon - mediate changes in regulatory dna 21 , 22 , and it may become evident with the sequencing of the genomes of more organisms like amphioxus with relatively short life cycles are sequenced to what extent such changes in regulatory dna mediate large evolutionary changes .\nthe amphi - alu sine from the foxd gene in an individual of branchiostoma floridae .\na. schematic diagram of the upstream regulatory region showing the foxd repeat region in cosmid mpmgc117o0129 , which we have shown is essential for directing expression of foxd to the notochord just upstream of the amphi - alu element , which is inserted into the foxd gene at base 1168 upstream of the atg start codon .\nthis element contains two binding sites for foxa2 which is also expressed in the notochord , but as it is not present in two other foxd alleles , it can not be essential for notochord expression .\nb. representative sequence variations of the amphi - alu sine from the foxd gene in cosmid mpmgc117o0129 and from six bac clones and two genomic traces from the trace archive database ( http://www.ncbi.nlm.nih.gov/traces/trace.cgi ? ) .\nthe amphi - alu sine in bac ch302 63l21 is located in the presumed upstream regulatory region of the tbx15/18/21 gene and that from ch302 119j21 within an intron of a hypothetical gene coding for a cyclic nucleotide gated cation channel .\nsince the other sequences are either from bac end sequencing or shot - gun sequencing , it is not possible as yet to determine if they are within regulatory regions of genes .\nthe amphi - alu sequence is shown in the reverse orientation of its insertion into the foxd locus to orient the polya stretches as polya tails ( double - underlining ) .\nthe 5 ' end of the alu element is shown as 1 , the alu sites are shaded in grey , two regions corresponding to the binding sites for rna polymerase on the trna - like region are underlined and the binding sites for foxa2 are shown by thick lines over the sequence the amphifoxd genomic region lacking the amphi - alu sine from a sequence in the trace archives of genbank ( gnl|ti|545126576 name : afsa504495.g2 ) .\nthe site corresponding to the insertion site of the amphi - alu sine in the foxd gene in cosmid mpmgc117o0129 is shown by the arrowhead .\nalignment of the sea urchin ( strongylocentrotus purpuratus ) trna for asparagine and the corresponding region of the amphi - alu element .\nthe regions with high identity to the a and b binding sites for rna polymerase iii are boxed .", "answer": "transposable elements of about 300 bp , termed \n short interspersed nucleotide elements or sines are common in eukaryotes . \n however , alu elements , sines containing restriction sites for the alui enzyme , have been known only from primates . here \n i report the first sine found in the genome of the cephalochordate , amphioxus . \n it is an alu element of 375 bp that does not share substantial identity with any genomic sequences in vertebrates . \n it was identified because it was located in the foxd regulatory region in a cosmid derived from one individual , but absent from the two foxd alleles of bacs from a second individual . \n however , searches of sequences of bacs and genomic traces from this second individual gave an estimate of 50 - 100 copies in the amphioxus genome . \n the finding of an alu element in amphioxus raises the question of whether alu elements in amphioxus and primates arose by convergent evolution or by inheritance from a common ancestor . \n genome - wide analyses of transposable elements in amphioxus and other chordates such as tunicates , agnathans and cartilaginous fishes could well provide the answer .", "id": 274} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndental materials contain a great variety of different monomers and additives.1 because of the complex chemical composition and the incomplete monomer \npolymer conversion , several components are leached out from each resin - based restorative material into the oral environment.2,3 this in turn may cause some adverse effects.4 previous studies have used in vitro cytotoxicity tests to evaluate the biological risks of resin composites used in dentistry.1,5 cytotoxicity tests have primarily focused on restorative materials such as glass ionomers , dental adhesives and composite resins.68 however , fewer studies on prosthodontic materials have been published , and investigations regarding the cytotoxicity of provisional prosthodontic materials are even more limited.5,9 provisional restorations are used in the interim between tooth preparation and fitting a definitive restoration . the length of time between preparation of teeth and cementation of final restorations can vary from a few days for straightforward cases , to several weeks or even , in the case of complex reconstruction , several months .\nprovisional restorations are generally essential to cover freshly cut dentine , stabilize the position of the prepared tooth , regain chewing function and phonation , maintain esthetic appearance and evaluate the minimal thickness of the definitive restoration .\nthey can also help stabilize the periodontal condition prior to definitive restoration.10 provisional materials can be classified by the type of resin .\nacrylic polymethyl or polyethyl methacrylates belong to the oldest group of provisional materials . the latest class of materials is formed by bis - acryl composite resins , which are comparable to composite resins used for direct restoration therapy.10 they consist of an organic matrix and inorganic fillers .\nbis - acryl composites produce less heat and shrinkage during polymerization than other resins , resulting in a better marginal fit.11 aesthetically they are reasonable and are more color stable than polymethyl or polyethyl methacrylates.12 most recently , visible light cured resins have been introduced based on urethane dimethacrylate .\nthese resins have good mechanical properties , being light cured , the operator has some control over the material s working time and colour is relatively stable but marginal fit can be poor.10,13 acrylates and mainly methacrylates were found to cause cytotoxic effects.14 evaluation of the cytotoxicity of dental resin materials showed a relationship between their composition and the degree of cytotoxicity.15 continuous cell lines , like l929 mouse fibroblasts are being routinely used for the testing of cytotoxic properties of dental materials because of their reproducible growth rates and biological responses.1 the purpose of this in vitro study was to evaluate the effect of current bis - acryl and urethane dimethacrylate based provisional materials on the fibroblast cell viability .\ntwo of the tested materials were bis - acryl based ( tempofit duomix , detax , germany & protemp 3 garant , 3 m espe , germany ) and one was urethane dimethacrylate based ( revotek lc , gc corporation , japan ) provisional restoration materials .\ntest specimens were prepared according to the manufacturers instructions in standard teflon discs , 5 mm in diameter and 2 mm of height .\nall specimens were prepared and handled under aseptic conditions to limit the influence of biological contamination on the cell culture tests .\nspecimens were prepared between mylor and glass slabs to minimize the oxygen inhibition and maximize the surface smoothness .\ntempofit duomix is a two - part base / catalyst , hand - mix , self - curing and bis - acrylic composite based provisional restoration material .\nbase and catalyst were extruded equal amounts by pressing onto piston in the dispenser onto mixing pad .\nprotemp 3 garant is a two - part base / catalyst , auto - mix , self - curing and bis - acrylic composite based provisional restoration material . using the garant dispenser ,\nthe base and catalyst were extruded directly into the teflon disc and after 2 min 30 sec curing completed .\nrevotek lc is a light cure single component sculptable composite resin for temporary restorations . using a spatula required amount of material dispensed and applied into the teflon disc .\nthe specimen was light - cured for 6 sec by led light curing unit ( led , bluephase , ivoclar vivadent , liechtenstein , austria ) .\nthe samples immersed in 7 ml culture medium for 24 hours at 37c to extract residual monomer or cytotoxic substances .\nthe culture medium containing material extracts were sterile filtered to use on the cell cultures .\nl929 fibroblast cell line ( atcc ccl 1 ) cultured in basal medium eagle ( bme ) , biological industries , israel ) containing 10% new born calf serum ( biochrom ag , berlin , germany ) and 100 mg / ml penicilin / streptomysin ( biological industries , israel ) at 37c in a humidified atmosphere of 95% air/5% co2 .\nconfluent cells were detached with 0.25% trypsin and seeded at a density of 510 well in 96-well plate at 37c under 5% co2 for 24h and .\nafter 24 hours incubation , culture medium was replaced with 200 l of culture medium containing material extracts of provisional restoration materials .\nthe succinic dehydrogenase activity has been shown to be reasonably representative of mitochondrial activity in the cells and reflects both cell number and activity.16 the old medium removed and cell cultures were rinsed with phosphate buffer saline ( pbs ) and 200 l aliquots of freshly prepared mtt [ 3-(4,5-dimethyl - thiazol-2-yl)-2,5-diphenyl - tetrazolium bromide , sigma aldrich , germany ] solution ( 0.5 mg / ml in bme ) were added to each well . after a 2h incubation period ( 37c , 5% co2 )\nthe supernatant was removed and the intracellulary stored mtt formazan was solubilized in 200 l dimethyl sulfoxide for 30 min at room temperature .\ntwelve replicate cell cultures were exposed to a constant concentration of a single material in at least two independent experiments .\nl929 fibroblast cell line ( atcc ccl 1 ) cultured in basal medium eagle ( bme ) , biological industries , israel ) containing 10% new born calf serum ( biochrom ag , berlin , germany ) and 100 mg / ml penicilin / streptomysin ( biological industries , israel ) at 37c in a humidified atmosphere of 95% air/5% co2 .\nconfluent cells were detached with 0.25% trypsin and seeded at a density of 510 well in 96-well plate at 37c under 5% co2 for 24h and .\nafter 24 hours incubation , culture medium was replaced with 200 l of culture medium containing material extracts of provisional restoration materials .\nthe succinic dehydrogenase activity has been shown to be reasonably representative of mitochondrial activity in the cells and reflects both cell number and activity.16 the old medium removed and cell cultures were rinsed with phosphate buffer saline ( pbs ) and 200 l aliquots of freshly prepared mtt [ 3-(4,5-dimethyl - thiazol-2-yl)-2,5-diphenyl - tetrazolium bromide , sigma aldrich , germany ] solution ( 0.5 mg / ml in bme ) were added to each well . after a 2h incubation period ( 37c , 5% co2 ) the supernatant was removed and the intracellulary stored mtt formazan was solubilized in 200 l dimethyl sulfoxide for 30 min at room temperature .\ntwelve replicate cell cultures were exposed to a constant concentration of a single material in at least two independent experiments .\nin contrast , protemp 3 garant group demonstrate full cell density in figure 2(c ) .\nthe results showed that , eluates of the revotek lc and protemp 3 garant lead to 99% and 101% cell survival . statistically revotek lc and protemp 3 garant were not cytotoxic for cells when compared to control group ( p>.05 ) .\ntempofit duomix was cytotoxic for cells when compared to control group and other tested materials ( p<.05 ) .\nthe literature contains descriptions of cell - culture tests with various cell types to establish cell damage caused by dental materials.17 in the present study the effect of two bis - acryl and one urethane dimethacrylate based commercially available provisional restoration materials on fibroblast cells were investigated by mtt test .\nfibroblasts are the targets of any chemical components that may be released from the dental restorative materials .\nl929 fibroblast cells were selected due to its availability , popularity and efficiency to grow in vitro.18 mtt assay is a well - established method for analyzing cell viability.16 the viability and proliferation of the cells are assessed by means of the functional state of the cell mitochondria.19 mitochondrial dehydrogenases in living cells reduce the yellow tetrazolium salt , mtt ( 3-(4,5-dimethyl ) thiazol-2-yl ) 2,5 diphenyltetrazolium bromide ) to blue mtt formazan , which is then retained in the cell .\nformation of the formazan product has been found to correlate well with number of viable cells.8,19,20 today , bis - acryl composites possess considerable amount of the market share for tooth colored provisional material .\nmain advantages of bis - acryl provisional materials include a lower curing temperature , reduced polymerization shrinkage ( 5% ) with improved marginal fit , and minimal odour and taste.13,21 the low setting temperature of these materials allows them to be used directly with decreased risk of pulpal injury.22 in addition , bis - acryls are gaining in popularity , in part because of their cartridge delivery system .\nthis dispensary method not only is convenient but also may allow for a more accurate and consistent mix.21 dental practitioners have clearly welcomed these products and very limited data can be available about their cytotoxicity and biocompatibility . in present study , two of the tested provisional restoration material was bis - acryl based which are chemically very similar to bisphenol - a - glycidyl methacrylate ( bis - gma ) composites . according to our results , eluates from tempofit duomix lead to 88% cell survival and when compared to control group and other tested materials it was cytotoxic for cells ( figure 2a b ) . on the hand protemp\n3 garant , the other bis - acryl based provisional material , was not cytotoxic for l929 fibroblast cells ( figure 2c ) .\nthe modifications include a newly developed monomer system , not with the rigid intermediate chain characteristic of some bis - gma homologues , but with a somewhat flexible chain in comparison to other synthetic resins ( espe technical product profile ) .\nhowever , manufacturer of tempofit duomix do not state any difference in monomer formulation . probably as most other bis - acryl\nbased provisional materials , the organic polymer matrix of tempofit duomix is composed of traditional monomers such as bis - gma , triethylene glycol dimethacrylate ( tegdma ) or similar monomer systems .\npatents may also hinder objective research.23 only available composition of the resin cements tested in this study .\ncurrent investigations reported the cytotoxic effects of some resin monomers , such as bis - gma , tegdma and urethane dimethacrylate ( udma).24,25 these resin monomers are able to deplete intracellular glutathione as well as interfere with the expression of some proteins , such as collagen i , osteonectin , and dentin sialoprotein , which play a fundamental role in the pulp repair.26,27 among the tested materials , revotek lc is the only udma based and light cure provisional material .\ngeurtsen et al1 reported that udma is as cytotoxic as bis - gma and tegdma .\nelution of residual monomers from resin materials related to degree of their polymerization , properties of resin composition , and chemistry of organic solvents in vitro situation.28 altntas et al29 demonstrated that leaching of udma was lower than bis - gma and tegdma from a resin cement .\nconsequently , in present study , eluates of the revotek lc showed similar cytotoxicity with control group .\nthe results of this study demonstrated that cytotoxic potential may vary among provisional materials . taking into consideration the limitations of this in vitro study\n, provisional restoration materials may have cytotoxic effects and should be selected carefully for clinical applications .", "answer": "objectives : the aim of the present study was to evaluate the cytotoxic effects of three different provisional restoration materials on fibroblasts . two bis - acrylic based [ tempofit duomix ( detax ) , protemp 3 garant ( 3 m espe ) ] and one urethan dimethacrylate [ revotek lc ( gc corporation ) ] based provisional restoration materials used.methods:materials were prepared according to the manufacturers instructions in standard teflon disks ( 25 mm ) and four samples were extracted in 7 ml of basal medium eagle with 10% new born calf serum and 100 mg / ml penicillin / streptomycin for 24 hours . \n the l929 fibroblast cells were plated ( 25.000 cells / ml ) in well plates , and maintained in a co2 incubator at 37c for 24h . after 24 hours \n , the incubation medium was replaced by the immersed medium in which the samples were stored and the l929 fibroblasts were incubated in contact with eluates for 24 hours at 37c for 24h . \n the fibroblast cell viability was analyzed by measuring the mitochondrial activity with the methyltetrazolium test ( mtt ) . \n twelve well used for each specimen and experiment repeated for two times . \n the data was statistically analyzed by mann - whitney u tests.results:the results showed that , revotek lc and protemp 3 garant were not cytotoxic for fibroblast cells when compared to control group ( p>.05 ) . \n however , tempofit duomix was cytotoxic for l929 fibroblasts when compared to control group and other tested materials ( p<.05).conclusions : taking into consideration the limitations of an in vitro study , our study indicate that provisional restoration materials might have cytotoxic effects on fibroblasts and should be selected carefully for clinical applications .", "id": 275} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nzonisamide ( zns ) is an antiepileptic drug that has recently been approved in many countries .\nit is also effective for the management of migraine , neuropathic pain , essential tremor , anxiety , and other conditions .\nrecently , zns has been approved as a new adjunctive therapy for motor complications of parkinson 's disease ( pd ) in japan .\nmore recently , zns was reported to be effective for the management of impulse control behavior in pd , suggesting potential effects on non - motor pd symptoms .\ndream enactment associated with aggressive , violent behavior can carry a serious risk of injury to patients , as well as to spouses or caretakers .\nwe describe a patient with pd who had vivid nightmares and dream - enacting behavior that resolved after treatment with zns .\nin 2009 , a 71-year - old man with a history of pulmonary surgery noticed tremor of the left hand and akinesia . in march 2010 , he showed features of moderate parkinsonism , including masked face , stooped posture , bradykinesia , left - side - dominant rigidity , and resting tremor .\nbradykinesia , rigidity , and resting tremor responded to treatment with pramipexole ( 0.5 mg / day ) . since july 2010 ,\nhis wife was awakened nearly every night because of the patient 's aggressive or violent behavior during the middle of the night .\nfor example , he suddenly flew up or walked , collided with furniture or walls , cried out , or exercised his limbs noisily .\nhe was often injured . on the nights he presented with this behavior , he remembered having vivid nightmares , such as being chased by a cat , bear , or his wife or of fighting with a thief or grandchild .\ninterviews with the patient 's wife indicated that this aggressive , violent behavior during the night occurred sometimes in 2009 . in april 2011 , stooped posture and lumbar pain developed , which were attributed to pramipexole .\nwe switched from pramipexole ( 1.0 mg / day , once before sleep ) to zns ( 25 mg / day , once before sleep ) .\nbefore switching to zns , motor and non - motor symptoms were as follows : the scores on parts i , ii , iii , and iv of the unified parkinson 's disease rating scale ( updrs ) were 3 , 5 , 17 , and 0 , respectively .\nthe scores on the mini - mental state examination ( 29/30 ) and frontal assessment battery ( 18/18 ) were normal .\nthe heart - mediastinum 123i - metaiodobenzylguanidine uptake ratio was significantly decreased . because he noticed reduced olfactory sensitivity\n, we assessed olfactory recognition ability by using the odor stick identification test for japanese ( osit - j ) , as described previously .\nbriefly , the osit - j tests for 13 kinds of odors familiar to japanese people ( curry , cooking gas , perfume , japanese cypress , india ink , menthol , nattou [ fermented soybeans]/sweaty socks , rose , putrid smell , wood , roasted garlic , condensed milk , japanese orange ) .\nwe asked the patient to choose an answer among four possible odor names , one of which was correct , plus \ndetectable but not recognizable and odorless. he could identify four odors ( perfume , curry , cooking gas , and condensed milk ) .\nthe identification rate was 33% , consistent with that of patients with olfactory disturbances ( 36 34% ) .\nthe score on the pittsburgh sleep quality index ( ranging from 14 for normal to 56 for unsleeping ) was 16 , and the 2-point increase above normal was ascribed to difficulty in sleeping caused by nightmares .\nhis wife was no longer awakened since the patient 's aggressive and violent behavior had resolved .\nwe obtained informed consent from the patient and tested whether pramipexole elicited nightmares or violent behavior .\nfirst , he was given pramipexole ( 0.5 mg / day ) in the context of stable doses of zns ( 25 mg / day ) for 2 weeks .\nour patient showed aggressive and violent behavior associated with vivid nightmares , which probably preceded such behavior , during the middle of the night .\nthis disorder strongly suggested a rapid - eye - movement sleep behavior disorder ( rbd ) . in our patient , who had rbd\ndopamine agonists can lead to vivid dreams , nightmares , and parasomnia - like motor activity , but rbd in our patient was not induced by rechallenge with pramipexole . in patients with pd ,\npramipexole was reported to be effective for rbd , but to worsen rem sleep electromyographic abnormalities on video - polysomnography .\none study showed that pramipexole did not improve rbd in pd , and the authors mentioned that rbd in pd may be either 2 different stages of the same condition or 2 completely different conditions .\nthis can explain our observations during treatment with pramipexole , but we believe that pramipexole did not alter rbd in our patient since the wife 's interviews indicated that rbd was evident before starting pramipexole .\nthis notion is supported by the results of a previous study showing that the frequency and severity of rbd were unaffected by pramipexole therapy .\nhowever , our finding raises an open question whether zns is useful for treating rbd in patients with early pd .\ndream generators are suppressed by inhibition of brainstem locomotor pattern generators , which can modify dream content in rbd .\ndopaminergic dysfunction may play a role in the pathophysiology of rbd and dopamine modulates the expression of locomotion and other rhythmic motor patterns in neural circuits known as central pattern generators . a zns - induced effect on the dopaminergic system\nmight have modulated or inhibited brainstem locomotor pattern generators , consequently suppressing vivid nightmares , leading to the resolution of dream - enacting behavior .\nour experience suggests that zns potentially might be effective for the management of vivid nightmares or dream - enacting behavior in patients with early pd .\nthe authors report no conflicts of interest . there was no financial disclosure related with this work .", "answer": "recently , zonisamide ( zns ) has been approved as a new adjunctive therapy for motor complications of parkinson 's disease ( pd ) . \n more recently , zns was reported to be effective for the management of impulse control behavior in pd , suggesting potential effects on non - motor pd symptoms . \n dream enactment associated with aggressive , violent behavior can carry a serious risk of injury to patients , as well as to spouses or caretakers . \n this report describes a patient with pd who had vivid nightmares and dream - enacting behavior that resolved after treatment with zns . \n the present case raises the question whether zns might potentially be effective for the management of vivid nightmares or dream - enacting behavior .", "id": 276} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe occurrence of screw loosening is reported to be 12.7% in single tooth restoration and 6.7% in partial fixed prostheses .\n23 jemt et al.4 observed that most of the screw loosening occurred within a year and the frequency of screw loosening was reduced over time .\nhenry et al.5 and khraisat et al.6 stated that screw loosening is more frequent in external type implants .\nin internal type connections , the stability of the prosthesis is obtained from the clamping force of the screw joint and the frictional force created by contact between the conical mating parts of the implant - abutment assembly .\nbecause of this connection , internal type implants have more favourable stress distribution , better stability , and superior resistance to lateral load.7 however , tsuge and hagiwara8 presented no significant difference between internal and external implant - abutment connections concerning their effect on the abutment screw loosening .\ntheoharidou et al.9 also reported that the frequency of screw loosening in single tooth restoration was 2.7% in external type implants and 2.4% in internal type implants ; this difference was not statistically significant .\nthe frequency of screw loosening is reduced over time , but still occurs in spite of recent advances in the design and screw materials .\nscrew loosening produces discomfort for patients ; therefore , methods to prevent screw loosening are needed .\none method for preventing screw loosening that is easily applicable to clinical practice is retightening .\ngradual functional loading causes sliding of the screw thread and relief of screw extension induced by preload .\ngradual reduction of preload below a critical point causes screw turning . applying a greater preload on the screw in the first phase of screw loosening\nsiamos et al.11 reported that in order to minimize the loss of preload , it is necessary to retighten the screw 10 minutes after the first screw tightening .\nhowever , the retightening procedure may change the shape of the abutment screw and the inner screw thread of the implant ; hence , stability during function may be affected.12 in addition , conflicting results on the effect of retightening have been reported . according to tzenakis et al.,13\nif the abutment screw is repeatedly retightened , a higher preload can be obtained because of surface wear that can lower the coefficient of friction .\nhowever , weiss et al.14 reported that repeated tightening / removal procedures decreased the reverse torque value ( rtv ) of screws .\nriccardi - copped et al.15 reported that repeated tightening and removal of titanium screws caused the rtv to decrease gradually .\nthe effect of screw retightening remains controversial and on the timing and frequency of retightening are lacking .\nthe aim of this study was to assess the effect of dynamic loading and screw retightening on rtv in external and internal connection type implants .\ntwenty external type implants ( diameter , 4 mm ; length , 10 mm ; sola , shinhung , seoul , korea ) and 20 internal type implants ( diameter , 4 mm ; length , 10 mm ; luna , shinhung , seoul , korea ) were used ( fig .\n1 ) . abutments for cementretained prostheses ( diameter , 5 mm ; gingival height , 5.5 mm ; esthetic abutment for external implant and duo abutment for internal implant , shinhung , seoul , korea ) were connected to each implant ( fig .\neach implant and abutment assembly was held in a customized jig in all testing procedures . using a digital torque controller ( mgt 12 , mark-10 co. , new york , ny , usa )\nafter 10 minutes , the assemblies were retightened with 30 ncm torque to compensate for embedment relaxation.11 after tightening the screws twice , an initial measurement of rtv was made .\nthe implant / abutment assemblies were divided into 4 groups ( 10 assemblies per group ) in order to evaluate the effect of intermittent retightening : 1 ) ext - n , external type implant with no retightening ; 2 ) ext - rt , external type implant with retightening ; 3 ) int - n , internal type implant with no retightening ; 4 ) int - rt , internal type implant with retightening .\nthe implant / abutment assemblies were fitted to the mounting base of a universal testing machine ( electroplus e 3000 , instron , washington dc , wa , usa ) with the long axis of the implant fixed at 30 degrees relative to the vertical axis ( fig .\nthe testing device delivered sine curved cyclic loading between 20 and 250 n at 14 hz for 100,000 cycles . in the groups with no retightening ( ext - n and int - n ) , the rtv was measured after 100,000 cycles of loading , while rtv was measured after 3 , 10 , and 100 cycles as well as every 20,000 cycles in the retightening groups ( fig .\n3 ) . for all statistical evaluations , spss version 20.0 , spss inc . ,\none - way analysis of variance ( anova ) was used for comparing rtv depending on the implant system and retightening . when the rtv was measured repeatedly after various loading cycles ,\ntukey 's test was used for post hoc comparisons , and the significance level was set at =0.05 .\nthe initial rtvs were 27.8 1.3 ncm in external implants and 25.1 1.9 ncm in internal implants .\nboth implant systems showed decreased rtvs when compared with the tightening torque value of 30 ncm .\nthe initial rtv of external implants was significantly higher than that of internal implants ( p<.05 ) .\nthe rtvs of all implant / abutment assemblies were significantly reduced after cyclic loading ( p<.05 , table 1 , table 2 ) .\nthe rtvs of the groups without retightening were 25.4 1.2 ncm in the ext - n group and 15.8 1.8 ncm in the int - n group .\nthe ext - n group showed a significantly higher rtv when compared with the int - n group ( p<.05 ) .\nthe rtvs of the groups with retightening were 23.8 1.8 ncm in the ext - rt group and 19.9 3.3 ncm in the int - rt group .\nthe ext - rn group showed a significantly higher rtv than the int - rn group ( p<.05 ) . in external implants\non the other hand , retightened internal implant / abutment assemblies showed superior rtvs when compared to internal implants with no retightening ( table 1 , table 2 ) .\nscrew loosening is the most frequently occurring mechanical complication of implant restorations.516 abutment screw loosening has been reported in a large number of studies with an incidence ranging from 2% to 15% of abutments .\n2359 screw loosening is caused by inadequate tightening torque , settling of implant components , inappropriate implant position , inadequate occlusal scheme or crown anatomy , poorly fitting frameworks , improper screw design / material , and heavy occlusal forces.171819 to overcome screw loosening and joint instability , many technical solutions have been suggested .\nfor example , new abutment screw designs and materials for maximizing preload,120 mechanical torque - applying instruments for optimizing tightening torque,21 precise implant components for antirotation , and internal conical connection implants with no micromotion or microgaps have been proposed . in the current study ,\nthe initial rtv was always smaller than the tightening torque ( 30 ncm ) in external and internal type implants .\nhaack et al.22 reported that most of the tightening torque is used to overcome the friction of the surface and only 10% of the tightening torque is used to generate preload .\nthey suggested that 75 - 80% of tightening torque remained in titanium or gold screws.22 kim et al.23 reported that the amount of remaining torque was affected by the screw material ( 77% remained in titanium alloy and 66% remained in gold alloy ) . for standardization of the results ,\nthe same titanium alloy was used for both internal and external abutment screws in the present study .\nthe results showed that the remaining torque was 90.9% in external implants and 83.3% in internal implants .\nthese relatively high remaining initial rtvs might have been caused by advanced milling technique and/or the screw design / material .\nin the current experiments , initial rtvs and post - cyclic loading rtvs were higher in external implants than in internal implants .\nthis is a result of the difference in connection type between the implants . in external implants ,\njoint stability is obtained by the tension of the screw , while it is achieved mainly by friction between the abutment and the implant in internal type implants.24 most of the tightening torque is used to produce preload in external implants,25 while in internal implants , tightening torque is distributed between friction with the abutment and preload on the screw .\nmoreover , internal implants are susceptible to the wedge effect , which arises when tightening torque and mechanical load are applied , leading to axial displacement of the abutment , so that the tensile force of the screw is lost and preload is decreased.232425 according to lee et al.24 and kim et al.,25 axial displacement of the abutment is greater in internal implants , while rtv is greater in external implants .\nalthough screws from the same manufacturer were used for standardisation , the screws for external implants have longer threads than those of the screws used for internal implants ( fig .\n1 ) . the thread - engaging surface may affect the preload in screw - tightening procedures .\nto our knowledge , no internal / external implant system manufactured by the same manufacturer offers either similar or identical screw shapes owing to the different inner structures of internal / external implants .\nalthough the 2 implant systems had different screw sizes and dimensions , the lengths of the engaging or the mating threads were similar in both.24 the upper part of the thread in the screw of the external implant was not in contact and just passed through the inner surface of the implant .\ncomparison of the groups with and without retightening after cyclic loading revealed no significant differences in rtvs in external implants .\nhowever , in internal implants , retightening resulted in higher rtvs than those found in implants without retightening .\nthese results can be explained by the difference in connection type between the implants and the number of times the implants were retightened . in internal type implants , less settling effect occurs during tightening and loosening procedures , because tightening torque generates less preload due to dissipation of force via friction between the abutment and the implant .\ntherefore , a greater number of retightening procedures allows more settling effect and making an adequate surface of the screw .\ncardoso et al.26 found that rtvs decreased as the number of insertion / removal cycles increased in external type implants .\nin contrast , tzenakis et al.13 reported an increase of preload in internal type implants .\ntherefore , retightening of screws is strongly recommended for joint stability , especially in internal type implants .\nthe appropriate number of retightening procedures is not clear from the results of previous studies .\ntzenakis et al.13 reported a gradual increase in gold screw preload from tightening for the first time to retightening 5 and 10 times in internal type implants . in the current study\nit should be noted that retightening more than 5 times is not recommended for the maintenance of preload . in the present study ,\nthis phenomenon was observed in both external and internal type implants . according to delben et al.,27 rtvs\nwere maintained constantly by retightening after every 100,000 cycles of loading in external type implants . according to binon and\nmchugh,28 the average daily number of mastication is about 2,700 and so 100,000 cycles corresponds to around one month . in the current study ,\nthe load cycle was decreased to 20,000 cycles ( corresponding to one week ) in order to infer the timing of retightening , because previous studies found no significant differences with 100,000 load cycles . in the current experiments ,\nrtvs decreased only 10 rounds of cyclic loading in external and internal type implants . in our previous study,24\nthus , axial displacement of the abutment screw can affect joint stability , especially in internal implants . to increase preload and secure joint stability ,\nit is recommended that retightening be performed after 10 loading cycles for both external and internal implants . moreover , retightening after 1 week is also profitable for internal type implants .\nthis study evaluated rtv according to retightening and cyclic loading in external and internal type implants .\ninitial rtv and postcyclic loading rtv were higher in external implants than in internal implants . in external type implants ,\nretightening did not produce a significant difference in rtv when compared with the non - retightening group after 100,000 rounds of cyclic loading . in internal type implants ,\nthe retightening group showed significantly increased rtvs when compared with the non - retightening group after cyclic loading .\na decrease in rtv occurred after only 10 rounds of cyclic loading , which represents the early stage of cyclic loading .\nafter 20,000 cycles of loading , rtvs were maintained constantly in both external and internal type implants .", "answer": "purposethe aim of this study was to evaluate the effect of cyclic loading and screw retightening on reverse torque value ( rtv ) in external and internal type implants.materials and methodscement - retained abutments were connected with 30 ncm torque to external and internal type implants . \n experimental groups were classified according to implant connection type and retightening / loading protocol . in groups with no retightening \n , rtv was evaluated after cyclic loading for 100,000 cycles . in groups with retightening , \n rtv was measured after 3 , 10 , 100 cycles as well as every 20,000 cycles until 100,000 cycles of loading.resultsevery group showed decreased rtv after cyclic loading . before and after cyclic loading , external type implants had significantly higher rtvs than internal type implants . in external type implants , retightening did not affect the decrease in rtv . \n in contrast , retightening 5 times and retightening after 10 cycles of dynamic loading was effective for maintaining rtv in internal type implants.conclusionretightening of screws is more effective in internal type implants than external type implants . \n retightening of screws is recommended in the early stage of functional loading .", "id": 277} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npelvic fractures and in particular crescent fracture dislocations , which are characterised by disruption of the sacroiliac joint with extension proximally as a fracture of the posterior iliac wing , usually occur as a result of high velocity trauma ( 1,2 ) .\nosteopenia and the associated loss of bone trabeculae decreases the elastic resistance of the osseous elements of the pelvis , thus making the pelvis a common location for insufficiency fractures ( 3 ) . as the general population ages , the number of osteopenic specific pelvic fracture patterns are likely to increase . in cases where surgical fixation is required ,\nless invasive techniques are beneficial in this older population ( 3 ) . the unique fracture pattern described in this report occurred as a result of the patient falling in such a way as to result in simultaneous sudden flexion of one hip with extension of the contra - lateral hip , into a position known in athletic terms as the front splits . the combination of the torque force produced by the fall and the patients reduced bone mineral density resulted in a unique , unstable pelvic fracture . to our knowledge\nthis is the first reported case of bilateral crescent fractures , and the first reported case of pelvic fracture as a result of this mechanism of injury .\nthe authors have obtained the patient 's informed written consent for print and electronic publication of this case report .\na 57 year old woman slipped while shopping resulting in a fall , where - upon her right hip flexed to 90 degrees and her left hip extended to 90 degrees , to a point where her perineum came to rest on the floor .\nthis particular fall resulted in a twisting or torque like force being transmitted through her pelvis as she fell .\nshe attributed the increased pain that she was experiencing to aggravation of her long standing back complaint . prior to her fall\nshe had attended the spinal clinic for her back pain and was scheduled for a bone scan with a view to progressing to facet joint blocks .\non attendance at the spinal clinic following her scan it was noted that her low back pain had become more pronounced and she required walking aides in the form of crutches to mobilise . on reviewing the bone scan ,\nfurther imaging , both plain film and computed tomography ( ct ) ( fig.1 & fig .\n2 ) revealed extensive pelvic fractures with displaced bilateral superior and inferior pubic rami fractures and bilateral posterior ring crescent fractures .\nshe had no previous fractures and prior to her fall worked as a care assistant .\ncoronal computerised tomography ( ct ) image demonstrating bilateral posterior iliac wing fractures and sacro - iliac joint disruption three - dimensional ct reconstruction showing both the bilateral crescent and superior and inferior pubic rami fractures following admission , routine blood parameters ( including bone profile ) were all normal and a pelvic mri scan out - ruled any intra - pelvic soft tissue lesions . open reduction and internal fixation of her anterior pelvic ring was undertaken through a stoppa approach , both rami fractures were reduced and plated anteriorly and superiorly . at this time bone and soft tissue samples from the anterior ring were sent for analysis . following reduction and fixation of her anterior pelvis , intra - operative fluoroscopy revealed that her posterior injuries were in an acceptable position .\na 3 cm long vertical incision was made over both anterior inferior iliac spines and supra - acetabular screws were placed from the anterior inferior iliac spines to the posterior inferior iliac spines to fix the bilateral iliac wing fractures .\ninlet radiograph at 16 months post surgery demonstrating solid fixation and bony healing post - operative recovery was uneventful .\nsubsequent dual energy x - ray absorptiometry scanning revealed mild osteopenia for which she is being managed medically .\nfinal follow - up at 16 months demonstrated that the fractures had healed , and the patient was pain free and mobilising unaided ( fig .\nthese injuries are rotationally unstable , there may also be some vertical displacement but this is limited by the sacrotuberous and sacrospinous ligaments , which typically remain intact ( 1,2 ) .\nour patient sustained bilateral crescent fractures and complete bony disruption of her anterior pelvic ring through inadvertently and suddenly performing what is known in athletic terms as the front splits , where one hip is flexed and the other extended to 90 degrees in neutral adduction / abduction .\nalthough this does not fit with the classic description of high energy trauma , the force imparted to the untrained individual s pelvis in performing such an act would be considerable .\nanother contributing factor is our patients post - operative diagnosis of osteopenia , the associated loss of bone trabeculae decreases the pelvic elastic resistance making it a common location for insufficiency fractures in post - menopausal women ( 4 ) .\nday et al ( 5 ) have classified crescent fractures according to the extent of sacroiliac joint involvement , with type i fractures entering the anterior third of the sacroiliac joint , type ii fractures involving the middle third and type iii fractures limited to the posterior third of the sacroiliac joint .\noperative stabilisation of these injuries is recommended and aims to achieve accurate reduction of the sacroiliac joint and stabilisation of the associated pelvic ring fracture , thus facilitating early mobilisation and minimising disability due to post - traumatic malunion and osteoarthritis or instability of the sacroiliac joint ( 2,3,6 - 9 )\n. however both reduced function and ongoing pain are commonly reported even after technically satisfactory surgery ( 2,7 ) .\npelvic insufficiency fractures are relatively common and should be suspected in older female patients with unexplained hip , groin , buttock , low back pain and/or difficulty with ambulation , particularly if there is any recent history of trauma ( 10 ) . while the majority of these insufficiency fractures may be treated conservatively our patient required surgical fixation due to the unstable nature of her injury . to our knowledge this is the first reported case of bilateral crescent fractures and also of a pelvic fracture occurring as a result of this unique mechanism of injury .", "answer": "a case is presented of a healthy 57 year old female who slipped and fell awkwardly into what is known in athletic terms as the front splits . as a result of her fall she sustained bilateral crescent and superior and inferior rami pelvic fractures . \n successful operative fixation was undertaken by a combination of open and percutaneous techniques . to our knowledge \n this is the first reported case of bilateral crescent fractures , and of a pelvic fracture as a result of this mechanism of injury .", "id": 278} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsupravalvar mitral ring is a circumferential ridge or membrane arising from the left atrial wall overlying the mitral valve and frequently attached to the mitral valve.1 variable in thickness and extent , the ring ranges from a thin membrane to a thick discrete fibrous ridge.2 the membranous variety may be difficult to detect because the membrane often adheres to the anterior mitral valve leaflet while remaining just proximal to the posterior mitral leaflet .\nadhesion to the valve may impair the opening of the leaflets , and this impairment may be the main mechanism of mitral valve inflow obstruction in some patients .\nin other patients , the ring may be large enough to protrude into the mitral valve inflow and cause obstruction .\nthe supramitral ring may initially be incomplete and eccentric , allowing for an unobstructed flow through the mitral valve .\nhowever , turbulence can cause a progressive increase in the supravalvar membrane or ridge thickness , worsening mitral inflow obstruction.3 the same mechanism is responsible for the acquired variety of supravalvar mitral stenosis , which occurs after mitral annuloplasty for the repair of mitral regurgitation .\nwe herein present a case of a supraventricular ring in a 17-year - old male , who presented with syncope .\nabout 15 years ago , he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair . in chest x - ray\nboth lungs were clear , and the electrocardiogram result showed normal sinus rhythm , had undergone right bundle branch block , and right ventricular hypertrophy .\ntransthoracic echocardiography , transesophageal echocardiography , and finally cardiac catheterization revealed ejection fraction of 5055% , pulmonary hypertension with pulmonary artery pressure ( pap ) of 80/40 mm hg , pulmonary capillary wedge pressure of 23 mm hg , gradient in the mitral valve plane of 40 mm hg , no residual vsd , no patent ductus arteriosus ( pda ) , bicuspid aortic valve , no aortic insufficiency , no aortic stenosis , no sub - aortic web , normal coronary arteries , mild mitral regurgitation , moderate to severe mitral stenosis , supra mitral valve ring , normal left ventricle size , moderate right ventricle enlargement , and moderate systolic dysfunction .\nthere was a free floating high redundant obstructive membrane in the left atrium that was attached to the mid portion of the anterior mitral valve leaflet and also in the medial and base of the posterior mitral valve leaflet and large papillary muscles in the left ventricle ( figure 1 ) .\nit also extended just adjacent to the lower limb of the left atrium appendage mouth with a small orifice ( 6 mm ) in the lateral side and also multiple small fenestrations ( by 2 dimensional echocardiography ) , resulting in a severely restricted diastolic flow ( mean peak gradient = 9.3 mm hg ) .\nthis web was not found in mri cine turbo - flash images acquired on a 1.5 t scanner ( magnetom vision - siemens ) in the four - chamber view ( 3a ) and the transverse plane , short - axis view ( figure 2 ) . the patient s ascending aorta , descending aorta , and aortic arch were tortuous with moderate narrowing of the descending aorta distal to the subclavian artery with a systolic gradient of about 30 mm hg , which was suggestive of insignificant coarctation of the aorta .\nafter heparinization , extracorporeal circulation was established between the venae cava and the ascending aorta . following a median sternotomy ,\nthere was a long supravalvar muscular band , which was resected ( figure 3 ) .\nsupravalvar mitral ring rarely occurs as an isolated defect ; other congenital heart defects coexist in 90% of patients .\nthe mitral valve itself is often abnormal and stenotic at the valvar or subvalvar level ; fusion of leaflets , a small valve orifice , and abnormal papillary muscles are common abnormalities .\nshone s complex is a combination of four congenital heart defects : supravalvar mitral ring , parachute mitral valve , subvalvar aortic stenosis , and aortic coarctation .\nother common associated lesions in patients with supravalvar mitral ring are ventricular septal defect ( vsd ) , pda , atrioventricular ( av ) canal defect , and tetralogy of fallout.4 uncommonly associated defects include atrial septal defect , cor triatriatum , left superior vena cava , unroofed coronary sinus , partial anomalous pulmonary venous drainage , pulmonary venous obstruction , double - orifice mitral valve , and wolff - parkinson - white syndrome.5 lesions such as transposition of the great arteries , atrioventricular discordance , and double - outlet right ventricle are occasionally complicated by a supravalvar left atrioventricular valvular ring .\nobstruction to the mitral inflow results from the reduced area of the mitral valve orifice .\nwhen clinically significant , a diastolic pressure difference occurs between the left atrium and the left ventricle . left atrial and pulmonary venous pressures increase , leading to exudation of fluid into the pulmonary interstitial , which increases lung stiffness .\nbreathlessness and tachypnea are secondary to the interstitial edema and diminished pulmonary compliance.6 in severe cases , frank pulmonary edema can occur.7 an associated atrial septal defect may decompress the left atrium , reducing or masking the severity of the mitral valve obstruction .\nassociated lesions such as vsd or pda , which increase the left ventricle output , exacerbate the manifestations of mitral inflow obstruction.8 conversely , a supravalvar mitral ring may be difficult to detect in conditions with a diminished pulmonary blood flow such as tetralogy of fallot.9 persistently elevated pulmonary venous hypertension leads to pulmonary arterial hypertension , rise in pulmonary vascular resistance , and eventual failure of the right ventricle and tricuspid regurgitation .\nit also deserves of note that predilection for race , age , and sex has not been found yet .\ntreatment is the surgical resection of the web , but balloon dilatation is reported to have been successfully performed under fluoroscopic and transesophageal echocardiographic guidance by some authors.10\npreoperative identification of a supravalvular mitral ring is the target for obtaining good surgical results . for the identification of this congenital heart disease ,", "answer": "supravalvar mitral ring is a rare congenital heart defect of surgical importance . \n the condition is characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve . \n it often substantially obstructs the mitral valve inflow . \n we herein introduce a case of a supravalvar mitral ring in a 17-year - old male , who was admitted to our hospital with cardiac syncope . \n he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair 15 years before . \n transthoracic echocardiography , transesophageal echocardiography , and finally cardiac catheterization revealed a neglected supravalvular mitral ring . \n the ring was resected in a second operation , and the patient was discharged from the hospital symptom free .", "id": 279} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmore recently , they have been used in autotransplantation procedures to replace non - restorable teeth .\nthe transplantation of third molars may help to maintain alveolar bone and enable endosseous implantation without requiring bone regeneration , fulfilling functional and aesthetic demands .\ninformation regarding morphology and number of roots may be especially beneficial for careful extraction and subsequent endodontic procedures in autotransplantation .\nrelatively few studies have been conducted on the root and canal morphology of mandibular third molars , and there is no available report that specifically examines the use of cone - beam computed tomography ( cbct ) .\ncbct was introduced for head and neck applications and consists of a conical radiographic source and a high - performance digital panel detector .\ncbct has been used in various applications , including measurements for gingival and dentogingival units , as a preoperative tool in decision making for furcation involvement , evaluation of the facial bony wall , estimation of cancellous bone density , clinical assessment of bone grafting , assessment of root length , and resorption of the root .\nit has been suggested that cbct data may provide a better basis for treatment plans .\nthe main purpose of this study was to investigate the root morphology of korean mandibular third molars , and to evaluate the prevalence of c - shaped ( gutter - shaped ) , two - rooted , and three - rooted mandibular third molars with distolingual roots .\nevaluations were performed on 60 male and 77 female patients whose mean age was 35.3 15.3 [ table 1 ] .\ndescriptive statistics of study population according to the age and gender an i - cat scanner ( imaging sciences international , hatfield , pa , usa ) with a spatial resolution of 10 line pairs per centimeter and an isotropic 0.4-mm voxel size was used for this study .\nserial axial cbct images were evaluated continuously by moving the toolbar from the floor of pulp chamber to the apex to determine the number of roots and their morphology , using commercially available software ( m - view , seoul , korea ) .\nthe incidences of mandibular third molars with one - root , c - shaped roots , two roots , or three roots were evaluated by age group , gender , and topology [ figures 14 ] . to evaluate the bilateral occurrence of one - rooted , c - shaped , and three - rooted mandibular third molars ,\nevaluations were performed only on the patients who had bilateral mandibular third molars ( patient n = 77 ) .\ncone - beam computed tomography images showing mandibular third molars with one root ( arrow ) mandibular third molars with one root with c - shaped canal ( arrow ) mandibular third molars with two roots ( arrow ) mandibular third molars with three roots having distolingual root ( arrow ) statistical analyses of the occurrences , according the contributing factors , were performed using the chi - square test .\ndata analysis was done with commercially available software ( pasw statistics 18 , spss inc . ,\nthe number and percentage of mandibular third molars evaluated in the study group are listed in table 1 .\none hundred and twenty - one teeth ( 56.5% ) were detected to have two roots .\nonly 3.7% of mandibular third molars had c - shaped roots , and 1.9% had three roots with distolingual roots . calculating the incidence of each type by using the total number of teeth in each age group as the denominator ,\nthe occurrence of three - rooted teeth in each affected age group ( 20 - 29 , 30 - 39 , 40 - 49 ) increased to a respective 1.0% ( 1/99 ) , 4.2% ( 2/48 ) , and 6.7% ( 1/15 ) .\nthe percentage of c - shaped roots for the age groups 20 - 29 , 30 - 39 , 50 - 59 , 60 - 69 was a respective 4.0% ( 4/99 ) , 2.1% ( 1/48 ) , 5.6% ( 1/18 ) , and 14.3% ( 2/14 ) .\nthe overall occurrence of the number of roots in each age group was reported to show significant difference [ p < 0.05 , table 2 ] , and the incidence of multi - rooted third molars tended to increase with patient age .\nanalysis of incidence of mandibular third molars with one - root , c - shaped root , two roots , or three roots according to age groups the classification of mandibular third molars by root number and gender is seen in table 3 .\nusing the total number of mandibular molars in male and female patients as the denominator , the incidences of one root ( 31.5% ( 29/92 ) for male versus 42.6% ( 52/122 ) for female ) , c - shaped root ( 4.3% ( 4/92 ) for male versus 3.3% ( 4/122 ) for female ) , two roots ( 63.0% ( 58/92 ) for male versus 51.6% ( 63/122 ) for female ) , three roots ( 1.1% ( 1/192 ) for male versus 2.5% ( 2/112 for female ) were similar between males and females ( p = 0.144 ) .\nclassification of mandibular third molars by root number and gender classification of mandibular third molars by number of roots and topology is done in table 4 .\nthe incidences of one root ( 37.3% ( 42/110 ) for right side versus 38.5% ( 40/104 ) for left side ) , c - shaped root ( 3.6% ( 4/110 ) for right side versus 3.8% ( 4/104 ) for left side ) , two roots ( 57.3% ( 63/110 ) for right side versus 55.8% ( 58/104 ) for left side ) , three roots ( 1.8% ( 2/110 ) for right side versus 1.9% ( 2/104 ) for left side ) appeared to be very similar between the right and left sides ( p = 0.919 ) .\nclassification of permanent mandibular third molars by root number and topology ( right and left side ) an analysis of bilateral and unilateral distribution of mandibular third molars with c - shaped roots , two roots , or three roots having distolingual roots is listed in table 5 . to evaluate the bilateral occurrence of one - rooted , c - shaped , two - rooted , and three - rooted mandibular third molars , only patients who had bilateral mandibular third molars\nthe incidence rate of each of these types was calculated using the total number of mandibular molars in each group ( the one - rooted , c - shaped , two - rooted , and three - rooted groups ) as the denominator .\nbilateral occurrence was more evident for all groups except for the three - rooted group .\ncalculated bilateral and unilateral distributions for each group are as follows : one - rooted group ( 79.4% ( 50/63 ) for bilateral distribution versus 20.6% ( 13/63 ) for unilateral distribution ) , c - shaped group ( 66.7% ( 4/6 ) for bilateral distribution versus 33.3% ( 2/6 ) for unilateral distribution ) , two - rooted group ( 85.4% ( 70/82 ) for bilateral distribution versus 14.6% ( 12/82 ) for unilateral distribution ) , and three - rooted group ( 0.0% ( 0/3 ) for bilateral distribution versus 100.0% ( 3/3 ) for unilateral distribution ) .\nanalysis of bilateral and unilateral distribution of mandibular third molars with c - shaped root , two roots or three roots having distolingual root\nthis study used cbct images to evaluate the number of roots and the morphology of 214 mandibular third molars in 137 korean individuals .\nthe mandibular third molar , the last tooth in the molar series , is reported to be associated with greater variation in root pattern and canal systems . it is widely accepted that mandibular molars usually have two roots : one located mesially and one distally .\nthis study showed that highest percentage of mandibular third molars ( 56.5% ) had two roots , which is consistent with previous reports that showed respective results of 53.0% and 53.4% .\nthe incidence of three roots found for this report was rare ( 1.9% ) , and the additional roots were found in the distolingual area .\nan additional root that is located distolingually is called radix entomolaris , and this is a morphological variant identified as an mongolian trait . an additional root located in the lingual area\nwe found that the overall occurrence of the number of roots according to age groups was significantly different ; specifically , the younger the group , the lower the incidence rate of multi - rooted teeth .\nfurther study with a larger number of patients may be needed to draw conclusions about this apparent trend .\ngender predilection for the presence of distolingual roots and c - shaped roots in mandibular third molars was also evaluated in this study .\nprevious reports have already found no significant differences in third molar development between males and females , and no significant relationship between the gender of the patient and the presence or absence of third molars has been found either .\ntopological predilection for the presence of either the distolingual root or c - shaped root in mandibular third molars is rarely reported in the literature .\nthis study observed very similar occurrences between the right and left sides of the same patient 's jaw .\nno significant side differences of mandibular third molar mineralization have been reported previously , and prior study found that left - right symmetry in the root development of the mandibular third molar was very high , with a correlation coefficient of 0.93 for males and 0.95 for females .\nanalysis was performed to evaluate the unilateral or bilateral occurrence of one - rooted , c - shaped , two - rooted , and three - rooted teeth in the mandibular third molars .\nmost patients ( 80.5% ) exhibited similar morphology on both their right and left mandibular sides .\na previous report indicated that 78.2% of the individuals studied possessed both mandibular third molars , while 11.3% had one and 10.5% had none .\nextraction of mandibular third molars is a common operation in oral and maxillofacial surgery , and many reports have been published related to this issue .\nvarious aspects such as the prevalence of caries experience , carious lesions , or restorations on the occlusal surface have been determined in asymptomatic third molars that have erupted to the occlusal plane .\nthe prevalence of caries in third molars is considered to be high as well as associated with patients caries experiences in first and second molars .\nthe morphology of mandibular third molars may be of interest to the operator for many procedures including surgical removal , autotransplantation for atraumatic procedures , and endodontic treatment .\ntooth autotransplantation using mandibular third molars is reported be a useful surgical method to replace non - restorable teeth , with a high long - term survival rate .\nrecently , phase - contrast radiography was used to assess the root morphology of mandibular third molars , and it was suggested that phase - contrast radiography may be more useful than conventional radiography for this purpose .\nthere was a high prevalence of two - rooted and one - rooted mandibular third molars from a korean population , and it was found that the incidence of multi - rooted third molars tended to increase with patient age .\nthese data regarding the occurrence and morphology of teeth roots will provide useful information to dentists for various dental procedures .", "answer": "objective : the purpose of this study was to investigate the morphology and number of roots of korean mandibular third molars , and to evaluate the prevalence of c - shaped , two - rooted , and three - rooted mandibular third molars using cone - beam computed tomography ( cbct).materials and methods : serial axial cbct images of the mandibles were gathered from 137 korean patients . \n the total number of roots in the mandibular third molars of these patients was measured , and both the incidence and the correlations between left- and right - side occurrences , as well as between males and females , were analyzed.results:most of the mandibular third molars either had two roots ( 56.5% ) or one root ( 37.9% ) . \n there was no significant difference regarding the incidence of the different types of roots according to gender ( female versus male ) or topology ( right versus left side ) . a higher percentage ( 80.5% ) of the patients had similar root morphology on both sides.conclusion:the morphology and number of 214 mandibular third molars were examined using cbct . \n there was a high prevalence of two - rooted mandibular and one - rooted mandibular third molars from this korean population . \n even though the anatomical variations in the mandibular third molars may not be high , these data regarding the occurrence and morphology of the roots will provide useful information to dentists performing these procedures .", "id": 280} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe main attributes of biological identity are sex , age , stature , and ethnic background of the individual , which are also called the big four in forensic context .\nhuman identification is of paramount importance , for both legal as well as humanitarian purpose .\nalbeit there have been tremendous advancements in forensic medicine , this remains a practical problem .\nthe use of dental identification has long been considered a reliable method , especially when other methods ( fingerprints ) fail because body conditions are not available , and over time , forensic odontology has emerged as a complete branch .\nteeth can survive and remain virtually unaffected long after other soft tissue and skeletal tissues have been destroyed .\nthe recognition of teeth as a tissue that withstands great variation in environment ( temperature upto 1600 c , humidity , and ph ) has lead to its application in personal identification .\nit has been observed in past time that dental tissues have witnessed its importance worldwide where it has contributed enormously in identification of victims in disaster , 80% of non - thai in tsunami in thailand and 20% in 26/11 incidence where 12 coordinated shooting and bombing attacks were carried by terrorists in mumbai , india 's most populous city on 26 november , 2010 were identified using teeth .\nother than this , it has been reported that renowned people like adolf hitler and indian prime minister rajiv gandhi were identified using tooth .\nseveral parameters have been proposed for sex determination to identify an individual from teeth , but none of them have proved its reliability .\nrecently , dna analysis in forensic have gained attraction , but it is expensive and time - consuming .\nthis prompted us to look for other methods of dental identification , which will be cost - effective yet reliable .\ntooth pulp is encased in a hard tissue casting , where it may be protected from detrimental effects of impact , trauma , and heat .\ndeveloped a technique using pulpal tissue stained with quinacrine mustard , specific for y chromosome to determine sex of an individual . in literature , there is scarcity of relevant studies that analyzed the effect of caries on viability of pulpal tissue in sex determination .\nso , keeping in mind this fact , present study was conducted to analyze the effect of caries on pulpal tissue stained with quinacrine hydrochloride with the application of fluorescent microscope .\nthis study was carried out in the department of oral pathology and microbiology , swami devi dyal hospital and dental college barwala , panchkula .\nthe study protocol was approved by the ethical committee of college before commencement of the procedure .\nfifty maxillary and mandibular permanent teeth that were indicated for extraction for periodontal and endodontic reasons were included in the study .\nstudy sample consisted of 25 male and 25 female teeth , which were further categorized into 5 groups of 10 each ( 10 from males and 10 from females ) based on the extent of caries progression .\ngroup a includes freshly extracted tooth specimens with no caries , group b consisted of tooth specimens with caries in enamel , group c comprised of tooth specimens with caries less than half way of dentin , group d consisted of freshly extracted teeth with caries more than half way of dentin , and group e includes freshly extracted tooth specimen with caries involving pulp . the teeth were examined radiographically and clinically for analyzing the various stages of caries progression [ figure 1 ] .\n( a ) sound teeth , ( b ) enamel , ( c ) less than half way of dentin , ( d ) more than half way of dentin , ( e ) pulp modeling wax was folded and made into a block .\nthe tooth was embedded on the modeling block . to remove the pulp , the crown\nit was adequately washed in normal saline to remove any calcified bone or dentine particles .\nthe pulp tissue was then transferred to the dry and clean conical centrifuge tubes containing 5 ml of fixative ( 3 methanol:1 glacial acetic acid ) and left as such for about half an hour to 2 hours for the fixation of the pulp cells .\nit was then crushed with the glass rod sufficiently to isolate the pulp cells . a suspension\nfive ml of fresh fixative was then added to re - suspend the pellet , and the process was repeated thrice till a clear suspension of the pulp cells was obtained .\nthin smears were prepared on chilled microscope slides of 1 mm thickness by the air - drying method i.e. , by dropping 2 - 3 drops of the above suspension on the slide from a distance of inches to get a homogenous population of cells .\nthe slide was mounted in buffer of ph 5.5 and was observed under leica dmr fluorescent microscope ( oil immersion in dark field at 40 ) by bv exciting method ( emitting a blue - violet color , mainly at 4.047a0 and 4.038a0 ) . only those cells which contained the characteristic y chromatin i.e. , a brightly fluorescent spot attached to the nuclear membrane were counted as positive cells while those which did not show any such fluorescent spot were labeled as negative .\nresults obtained were subjected to statistical analysis by using independent t - test using spss ( version 9.0 ) software .\nthe tooth was embedded on the modeling block . to remove the pulp , the crown\nit was adequately washed in normal saline to remove any calcified bone or dentine particles .\nthe pulp tissue was then transferred to the dry and clean conical centrifuge tubes containing 5 ml of fixative ( 3 methanol:1 glacial acetic acid ) and left as such for about half an hour to 2 hours for the fixation of the pulp cells .\nit was then crushed with the glass rod sufficiently to isolate the pulp cells . a suspension\nfive ml of fresh fixative was then added to re - suspend the pellet , and the process was repeated thrice till a clear suspension of the pulp cells was obtained .\nthin smears were prepared on chilled microscope slides of 1 mm thickness by the air - drying method i.e. , by dropping 2 - 3 drops of the above suspension on the slide from a distance of inches to get a homogenous population of cells .\nthe slide was mounted in buffer of ph 5.5 and was observed under leica dmr fluorescent microscope ( oil immersion in dark field at 40 ) by bv exciting method ( emitting a blue - violet color , mainly at 4.047a0 and 4.038a0 ) . only those cells which contained the characteristic y chromatin i.e. , a brightly fluorescent spot attached to the nuclear membrane were counted as positive cells while those which did not show any such fluorescent spot were labeled as negative .\nresults obtained were subjected to statistical analysis by using independent t - test using spss ( version 9.0 ) software .\nthis study was done to evaluate the use of the fluorescent body test as a diagnostic test for sex determination .\ntable 1 showed sensitivity , specificity , positive predictive value , negative predictive value , and efficiency of each of the five groups .\nthe values obtained were highest for sound teeth with caries in enamel and value decreases with the progression of the caries .\ntable 2 depicted that fluorescent bodies were found to be more in sound teeth in males as the caries increase , the mean percentage of fluorescent bodies observed decreases in males .\nwe also observed the fluorescent spots in females , and the value of the spot increases in female as the caries progresses , thereby giving false positive results in females [ figure 3 ] .\nthe p value were found to be significant for sound teeth and teeth with caries in enamel and involving less than half the way of dentin , whereas it was non - significant for teeth involved with further caries involvement .\ndiagnostic utility of fluorescent body in identifying gender percentage of fluorescent bodies ( in % ) in different groups fluorescent photomicrograph showing bright fluorescent cell in males representing y chromosome fluorescent photomicrograph representing faint fluorescence in females\ndespite the fact that tremendous research work is carried out to determine a reliable method , but none have proven its efficacy .\nthe most reliable means of identification include fingerprints , dental comparisons , and biologic methods such as dna profiling . in some cases\n, however , fingerprints are not available from the deceased , or ante - mortem prints can not be obtained . sex determination from skull\nis highly unreliable although number of workers have described differences in the size of male and female teeth , such measurements seem unlikely to be used to determine the sex of an individual .\nso , a technique has been developed , which may offer a solution whenever soft tissue remains can be recovered .\ncasperson et al . showed that chromosome stained with quinacrine mustard fluoresced differentially along their length when viewed in ultraviolet light and the human y chromosome fluoresced more brightly than other chromosomes .\nhe suggested that alkylating agents like quinacrine acts on the dna portion rich in guanine and accumulate there .\nthis technique has been used in forensic science for sex determination from dried blood stains , saliva , and hair .\nthus , it might be applicable to sex determination from tooth pulp some time after death , because the teeth are a stable part of the skeleton and the pulp tissue is well - protected .\nseno and ishizu carried out the detection of y chromosome in the nuclei of dental pulp .\nthey found that f- body positive rate in the nucleated cells of male dental pulp was over 30% , even with the male teeth as old as 5 months , after the extraction . with female teeth ,\ntypical f - body can not be detected , and f - body like spot has been observed in 0.4% of cells , indicating that there can be no error in the identification of male tooth from that of female one , even such an f - body like spot is taken as an f - body itself .\npresent study revealed that in males , 60 - 75% fluorescent y bodies [ figure 2 ] were observed in sound teeth ( mean 69.4% bodies ) , 59 - 70% bodies in tooth with caries in enamel ( mean 64.2% bodies ) , 19 - 53% in teeth with caries in half way of dentin ( mean 39.8% bodies ) , teeth with caries involving more than half way of dentin and involving pulp showed 13 - 29% , 1 - 19% ( mean 21.8% , 6.37% bodies ) off bodies respectively as shown in table 2 .\nseno and ishizu showed a range of 56 - 72% fluorescent y bodies in freshly extracted sound teeth , which are in accordance to sound teeth in this study .\npseudo y body in the present study [ figure 4 ] in females were found to be in the range of 0 - 12% ( mean 5.2% ) , 0 - 12% ( mean 5.2% ) , 14 - 22% ( mean 17.8)% , 12 - 22 ( mean 16.8% ) , and 7 - 15% ( mean 11.6% ) for sound teeth , teeth with caries in enamel , caries in half way of dentin , caries involving more than half way of dentin caries , and caries involving pulp , respectively , as shown in table 2 .\nfluorescent photomicrograph representing artifacts or pseudo f - bodies in females discrepancy between various studies could be attributed to random inclusion of carious and non - carious teeth .\nso , the present study considered the effect of caries on fluorescent body test as literature ( when searched via pubmed and medline ) revealed lack of studies analyzing this fact . from present study , it can be inferred that as the caries progresses from enamel to dentin and further to pulp tissue , the sensitivity and specificity of determining y chromosome decreases [ table 1 ] .\nwhen the caries have involved only enamel or half the way of dentin , it has shown significant difference in fluorescent body test determining males and females , unlike when it involved more than half way of dentin and pulp where the difference is non - significant [ table 2 ] .\nthe decrease in y body could be attributed to the fact that cariogenic bacteria alter the microenvironment of pulp , resulting in alteration in fluorescent staining . as the caries progresses , the inflammatory processes in the pulp are initiated , as the inflammation progresses the internal architecture of the cell is lost , and is also characterized by necrotic poorly stained cellular debris .\nmany workers attributed the appearance of fluorescent bodies in females to artifacts , whereas others ascribed it to the presence of fluorescent debris .\nit was necessary to smear pulp cells thinly to prevent masking the fluorescent y chromosomes by fluorescent debris .\nsex determination by fluorescent staining of the y chromosome is a reliable technique in teeth with healthy pulp tissue or caries with enamel or upto half way of dentin .", "answer": "aims : to determine and compare the reliability of pulp tissue in determination of sex and to analyze whether caries have any effect on fluorescent body test.materials and methods : this study was carried on 50 maxillary and mandibular teeth ( 25 male teeth and 25 female teeth ) , which were indicated for extraction . \n the teeth are categorized into 5 groups , 10 each ( 5 from males and 5 from females ) on the basis of caries progression . \n the pulp cells are stained with quinacrine hydrochloride and observed with fluorescent microscope for fluorescent body . \n gender is determined by identification of y chromosome fluorescence in dental pulp.results:fluorescent bodies were found to be more in sound teeth in males as the caries increase the mean percentage of fluorescent bodies observed decreases in males . \n we also observed the fluorescent spots in females , and the value of the spot increases in female as the caries progresses , thereby giving false positive results in females.conclusion:sex determination by fluorescent staining of the y chromosome is a reliable technique in teeth with healthy pulps or caries with enamel or up to half way of dentin . \n teeth with caries involving pulp can not be used for sex determination .", "id": 281} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 16-month old , baby girl , weighing 9.5 kg and measuring 74 cm , visited the hospital because of a cough . in a chest radiograph\ndone under the suspicion of an upper respiratory infection , a round foreign object with a diameter of 21 mm was detected in the upper esophagus ( fig .\n1 ) . in a sleep endoscopy , it was confirmed to be a circular battery ( fig .\n2 ) , and ingestion was estimated to occur three days prior to the hospital visit , and it was determined that endoscopic removal would not be easy .\nthe infant had no underlying disease , and glycopyrrolate 0.05 mg was i m injected 30 minutes before arriving at the operating room as premedication for the anesthesia .\nthe infant was monitored by ecg , non - invasive blood pressure ( nibp ) , and a pulse oximetry , and before anesthesia , her blood pressure was 85/61 mmhg ; her heart rate was 160 beats / min with 100% oxygen saturation .\n10 mg of ketamine was iv injected and after loss of consciousness , 5 mg of rocunium was iv injected .\nwhen the muscles were sufficiently relaxed , an uncuffed endotracheal tube with a 4 mm inside diameter was intubated .\nafter intubation , both lungs were checked through a stethoscope and found to be normal , and the endotracheal tube was set to 11 cm in accordance with the top front teeth .\nanesthesia was maintained by 2 l / min of air , 2 l / min of o2 , and 2.0 - 3.5 vol% of sevoflurane .\nthe tidal volume was 90 ml ; respiratory rate was 18/min through volume - controlled mechanical ventilation to maintain an end - tidal co2 ( etco2 ) pressure of 35 - 40 mmhg and the peak inspiratory pressure ( pip ) at this point was 19 cmh2o .\nan adult endoscope with a 9 mm outer diameter was used for the removal procedure because the hospital did not have a pediatric endoscope with forceps .\n2 minutes after inserting the endoscope , severe abdominal inflation was observed , and pip increased up to 28 - 30 cmh2o with the tidal volume decreasing to less than 50 ml .\nthe battery had caused an inflammatory change and conglutinated onto surrounding tissue in the esophagus , and 3 minutes after inserting the endoscope , oxygen saturation decreased to 80% , and etco2 pressure rose to 70 mmhg therefore the surgery was stopped and the endoscope was removed . by manual ventilation using 100% oxygen , oxygen saturation was recovered to 100% and etco2 pressure to 40 mmhg , and thereafter , the endoscope was reinserted . in the second attempt of the procedure ,\nmanual ventilation was done instead of mechanical ventilation . however , 1 minute after the insertion of the endoscope , a sudden strong resistance was felt in the reservoir bag , and the tidal volume was less than 20 ml despite applying more than 35 cmh2o for the pip .\noxygen saturation dropped below 60% so the procedure could not be continued ; therefore , the endoscope was removed again . here , a pip of 25 - 30 cmh2o and a tidal volume of 50 ml were maintained .\nthe endoscope was reinserted after recovering oxygen saturation to 100% , but due to the increased airway pressure , ventilation was not possible , and oxygen saturation dropped back down to less than 40% .\nthe authors suspected the possibility of tef considering the period of intake and the excessive air volume seen in the stomach in the chest radiograph taken before the surgery .\nhence , the endotracheal tube was inserted until one lung ventilation was possible and then retreated while auscultating to secure onto the location where the pulmonary sound from both lungs became equal .\nthe adjusted position of the endotracheal tube was 15 cm based on the top front teeth .\na pip of 25 - 30 cmh2o and a tidal volume of 80 - 100 ml were maintained . in the next insertion of the endoscope ,\na pip of 30 cmh2o and a tidal volume of 50 ml were maintained but abdominal inflation was excessive so air in the stomach was partially removed with the endoscope , and the operating doctor was required to use the minimal amount of air for the surgery to proceed .\na pip of 25 - 30 cmh2o , a tidal volume of 50 - 80 ml , and oxygen saturation of 100% were maintained during the procedure , and the battery was removed . after the removal of the battery , the vital signs were blood pressure 96/69 mmhg , heart rate 152 beats / min , and 100% oxygen saturation .\nthe patient was not extubated but moved to postoperative intensive care , and after pediatrics observed vital signs for about 3 hours to verify that there were no abnormalities , extubation was done .\nsubsequent vital sign checks and physical exam were normal , and there were no abnormalities found in the blood test .\nmoreover , the right main bronchus appeared on the screen in the postoperative esophagography ( fig .\n3 ) , and the chest ct scan found tef at 1.4 cm in the upper carina ( fig .\n4 ) . the guardian wanted to have surgery for tef at another hospital ; therefore , 3 days after the surgery , she was transferred .\ningested batteries usually pass through the gastrointestinal tract and are defecated in a few days , but when it is caught in the esophagus , the moist environment of the esophagus allows for the discharge of substances inside the battery together with electrical discharges , which can cause tissue damage of the esophagus .\nin addition , necrosis can develop in the mucus membrane of the esophagus due to the pressure from the battery , and these can trigger complications such as esophageal burns , perforation , and tef .\nmore severe complications arose in cases where the diameter of the battery was larger than 20 mm and the infant was younger than 4 years old .\nthe main factors that cause severe complications in battery ingestion were the size ( larger than 20 - 30 mm ) and components of the battery .\nespecially if the negative terminal of the battery is attached to the tissue , it can lead to more severe results .\nin addition , lithium batteries cause the most severe damages , and it was reported that in a dog 's esophagus , necrosis developed in the trachea within an hour . in this case study , the corroded battery and inflamed mucous membrane of the esophagus were confirmed in endoscopy before the surgery , but tef could not be tested and confirmed due to the urgency of the surgery .\nit is reported that esophageal burns start 4 hours after battery ingestion and perforations that form fistulas start in 6 hours . since the estimated ingestion period for this case was 3 days , it is enough time for tef to develop .\nthe infant in this case study did not have respiratory difficulties before of the surgery , but ventilation failure during the surgery was because the endotracheal tube was fixed at 11 cm at first .\nthe tef located approximately 2.6 cm under the end of the endotracheal tube allowed the inhalation gas for the anesthesia to flow into the stomach leading to abdominal inflation , and consecutively , the air injected for the endoscopic surgery flowed over to the respiratory tract to greatly increase the airway pressure .\nafterwards , when the endotracheal tube was inserted deeply into the carina , the tube was located past the tef so the influence of tef was eliminated for the decrease in airway pressure . when there is tef , it is important to position the endotracheal tube above the carina and below the tef to maintain anesthesia .\nthis is because effective ventilation would not happen due to a loss of the tidal volume through the fistulous openings in the tef , the contents of the stomach being aspirated into the lungs , and excessive positive pressure ventilation when inducing anesthesia can cause abdominal inflation and cardiovascular suppression .\nhowever , in our case , ventilation was not completely recovered even when the endotracheal tube was inserted deeply to eliminate the influence of tef , and this is thought to be from accompanying ventilation failure from the endoscope .\nthis ventilation failure can be caused by pressure on the pharynx and the trachea from the weight of the endoscope , or motor abnormality of the diaphragm due to abdominal inflation from the injected air .\nwengrower et al . reported that approximately 7% of infants who had endoscopic procedures under sedation or anesthesia exhibited temporary desaturation .\nthere are reports that an infant with a similar height and weight developed ventilation failure from a tee probe with outer diameter of 10 8 mm . in our case , the fact that direct pressure on the respiratory tract was applied by using an adult endoscope with a 9 mm diameter and that air had to be injected continually since the battery had attached itself to the esophagus and was hard to remove could have been some other causes for the excessive airway pressure , ventilation failure , and hypoxemia .\nwhen upper gastrointestinal endoscopic procedures were done on 99 infants of 0.9 - 10.1 kg using an endoscope with a 5.2 mm outer diameter , only 1 infant with global developmental delay exhibited hypoxemia , and gryboski recommended using endoscopes with a 5 mm outer diameter on infants with esophageal diseases .\nit is important to use pediatric endoscopes with the smallest possible outer diameters to prevent hypoxemia during endoscopic procedures on infants . since the removal of foreign objects in the esophagus of infants\nare usually done under general anesthesia , anesthesiologists need to anticipate ventilation failure and hypoxemia from the physical pressure from the procedural equipment and the excessive injection of air and proceed with anesthesia under close cooperation with the operating surgeon .\nespecially when a battery has been ingested , it is necessary to be aware that there could be complications such as tef in the location where the battery is depending on the battery 's components , size , and ingestion period .\nin addition , to more effectively block the mutual flow of air and anesthetic gas towards either the esophagus or the trachea in the case of a potential tef , a cuffed endotracheal tube should be chosen preferentially and special caution should be taken to fix the position of the tube and in selecting a suitable size for the endoscope used in the procedure .", "answer": "ingestion of disk batteries may have serious complications such as esophageal burn , perforation , and tracheoesophageal fistula , particularly when the battery is caught in the esophagus . \n proper placement of the tracheal tube is critical when tracheoesophageal fistula was occurred from esophageal impaction the battery . \n endoscopy of upper gastrointestinal tract in infants and children is an important and effective tool for the diagnosis and treatment of foreign body ingestion . but \n upper gastrointestinal endoscopy in infant and children has very high risk of tracheal compression and airway compromise . \n we present a case of ventilatory compromise during insertion of the upper gastrointestinal endoscopy in 16-month - old child with tracheoesophageal fistula secondary to disk battery ingestion .", "id": 282} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na total of 30 mabs that were either developed or in - licensed by companies are currently undergoing evaluation in late - stage studies ( tables 1 and 2 ) .\nfive of these ( brodalumab , mabp1 , moxetumomab pasudotox , tildrakizumab , rilotumumab ) transitioned into phase 3 studies during the period from late 2012 to april 2013 .\nbrodalumab ( amg827 , amgen ; khk4827 , kyowa hakko kirin ) , a human igg2 targeting the interleukin ( il)-17 receptor , is undergoing evaluation in three phase 3 studies ( amagine-1 , -2 , and -3 ) of patients with psoriasis .\nthe amagine-1 study ( nct01708590 ) is evaluating the efficacy , safety , and effect of withdrawal and retreatment with brodalumab in patients with moderate - to - severe plaque psoriasis . in this study , either of two doses ( 140 mg or 210 mg ) or placebo is administered subcutaneously ( sc ) every two weeks until week 12 , when patients are rerandomized to placebo or continued treatment .\nthe estimated primary completion date for the study is march 2014 . in the amagine-2 ( nct01708603 ) and amagine-3 ( nct01708603 ) studies ,\nthe efficacy and safety of induction and four maintenance regimens of brodalumab compared with placebo and ustekinumab in patients with moderate - to - severe plaque psoriasis is being evaluated .\nthese studies have estimated primary completion dates of august and september 2014 , respectively . note : table compiled from information available as of april 25 , 2013 .\nabbreviations : cd , cluster of differentiation ; il , interleukin ; pcsk9 , proprotein convertase subtilisin / kexin type ; sle , systemic lupus erythematosus . note : table compiled from information available as of april 25 , 2013 . * in - licensed\n; national cancer institute is sponsoring the phase 3 study in hairy cell leukemia patients .\nabbreviations : all , acute lymphoblastic leukemia ; cll , chronic lymphocytic leukemia ; hgf / sf , hepatocyte growth factor/ scatter factor ; nhl , non - hodgkin lymphoma ; nscl , non - small cell lung ; vegfr2 , vascular endothelial growth factor receptor 2 . a first phase 3 study ( nct01767857 ) of mabp1 ( xilonix , xbiotech , inc . ) , a human mab targeting il-1 , was recruiting patients as of march 2013\n. the study will evaluate overall survival of metastatic colorectal cancer patients with cachexia who are administered the mab as a monotherapy .\nthe effects of mabp1 administered intravenously ( iv ) every two weeks , plus best supportive care will be compared with those of megestrol acetate administered daily plus best supportive care .\nthe difference between the study arms in median overall survival from baseline to 18 mo will be compared .\nthe recombinant immunotoxin moxetumomab pasudotox ( cat-8015 , astrazeneca ) is undergoing evaluation in a phase 3 study ( nct01829711 ) of patients with relapsed / refractory hairy cell leukemia .\nthe study is sponsored by the national cancer institute ( nci ) ; the mab is currently licensed to astrazeneca . in 2004 , nci licensed moxetumomab pasudotox to genencor , inc .\nthe mab was then acquired in 2005 by cambridge antibody technology , which was itself acquired by astrazeneca in 2006 .\nmoxetumomab pasudotox comprises a mouse disulfide stabilized variable fragment with the variable heavy domain fused with a 7-mer linker and the pseudomonas aeruginosa exotoxin a pe38 fragment . in the phase 3 study\n, patients will receive 40 g / kg of the immunotoxin administered iv over 30 min on days 1 , 3 , 5 of each 28 d cycle until complete response , progressive disease , initiation of alternate therapy or unacceptable toxicity is observed .\ninitiated in march 2013 , the study s estimated primary completion date is december 2014 .\ntwo phase 3 studies of tildrakizumab ( sch900222/mk-3222 , merck ) , a humanized mab targeting the p19 subunit of il-23 , are recruiting patients .\ninitiated in december 2012 , nct01722331 is a 64-week study to evaluate the efficacy and safety / tolerability of sc administration of tildrakizumab in patients with moderate - to - severe chronic plaque psoriasis .\npatients receive 100 mg or 200 mg tildrakizumab at week 0 and week 4 , and then every 12 weeks until study end or participant discontinuation .\npatients receive the same doses of tildrakizumab , but the study includes 50 mg etanercept as well as placebo as comparators .\nthe two phase 3 studies have estimated primary completion dates of june and july 2015 , respectively .\nrilotumumab ( amgen ) is a human igg2 targeting human hepatocyte growth factor / scatter factor ( hgf / sf ) that blocks binding of hgf / sf to its receptor met , thereby inhibiting the met signaling pathways .\nthe mab is undergoing evaluation in a phase 3 study ( nct01697072 ) of chemotherapy ( epirubicin , cisplatin and capecitabine ) with rilotumumab or placebo for untreated advanced met - positive gastric or gastresophageal junction adenocarcinoma .\nrilotumumab or placebo is administered iv at doses of 15 mg / kg every 21 d. the primary outcome measure is overall survival in a time - frame of three years .\ninitiated in october 2012 , the estimated primary completion date for the study is december 2015 .\nrecently announced results for three late - stage studies of two mabs for cancer ( farletuzumab , naptumomab estafenatox ) and tabalumab , a mab treatment for autoimmune disorders , indicate that clinical endpoints were not met .\nfarletuzumab ( morab-003 , morphotek / eisai ) is a humanized igg1 mab that targets human folate receptor , which is overexpressed in most epithelial ovarian cancers , as well as some forms of endometrial , breast , renal , lung and colorectal cancers .\nthe primary endpoint of progression - free survival ( pfs ) was not met in the phase 3 far-131 study ( nct00849667 ) of farletuzumab in combination with carboplatin and a taxane in patients with platinum - sensitive epithelial ovarian cancer in first relapse .\npatients received placebo or farletuzumab at either 1.25 mg / kg or 2.5 mg / kg weekly for ~six cycles .\nalthough the primary endpoint was not met , a trend toward improved pfs was observed in some patient subsets in a post - hoc analysis .\nthe safety and efficacy of farletuzumab in combination with a platinum containing doublet in chemotherapy - nave subjects with stage iv adenocarcinoma of the lung are being evaluated in a phase 2 study ( nct01218516 ) . as announced in january 2013 by active biotech ab , initial results of a phase 2/3 study ( nct00420888 ) of naptumomab estafenatox ( abr-217620 , anyara ) in combination with interferon as a treatment for advanced renal cell carcinoma indicated that the study did not achieve its primary clinical endpoint of overall survival in the intention - to - treat cohort .\na confounding factor was the presence of high levels of pre - formed anti - drug antibodies found in a majority of patients in this , but not previous , studies .\na doubling of pfs and overall survival occurred in the 25% of patients who had low or normal levels of base - line il-6 and expected levels of anti - drug antibodies .\nnaptumomab estafenatox is composed of an antigen - binding fragment ( fab ) that targets metastasis - associated 5t4 fused to a mutated form of staphylococcal enterotoxin a ( sea / e-120 ) .\nphase 3 studies of tabalumab ( ly2127399 , eli lilly and co. ) as a treatment for ra have been discontinued due to lack of efficacy .\ntabalumab , a human igg4 targeting b - lymphocyte stimulator , was being evaluated in five phase 3 studies of ra patients .\ntabalumab in combination with bortezomib and dexamethasone is also being evaluated in a phase 2/3 study ( nct01602224 ) of patients with previously treated multiple myeloma .\nhistorically , ~50% of mabs in the commercial clinical pipeline have been studied as cancer agents ; however , ~67% of the current cohort of mabs at phase 3 is in studies for non - cancer indications ( table 1 ) .\nthese 20 mabs are human or humanized , with more than half ( 55% ) targeting an interleukin or an interleukin receptor .\nthe mabs are being developed as treatments for immunological disorders such as ra , sle , ms and psoriasis , but also for hypercholesterolemia , cachexia and alzheimer disease . reflecting the overall greater challenge of demonstrating safety and efficacy in cancers ,\nthe molecular types of the 10 mabs in late - stage studies of cancer ( table 2 ) are more diverse than those for non - cancer indications .\nof particular note is the inclusion of a toxin in three molecules ( naptumomab estafenatox , moxetumomab pasudotox , inotuzumab ozogamicin ) and use of less than a full - length sequence for three molecules ( naptumomab estafenatox , moxetumomab pasudotox , onartuzumab ) . the majority ( 70% ) of the 10 product candidates\nare in studies of solid tumors , with the remainder undergoing evaluation as treatments for hematological cancers .\nthe number of anti - cancer mabs at phase 3 is likely to increase in the next 35 y as more adcs move into and through the clinical pipeline . \n\nmabs will continue to track the progress of antibody therapeutics in clinical study throughout 2013 , and we look forward to reporting on results that may be released during the year in which are the antibodies to watch in 2014 ?", "answer": "the transitions of antibody therapeutics to late - stage clinical development , regulatory review and the market are proceeding at a rapid pace in 2013 . since late 2012 , two monoclonal antibody ( mab ) therapeutics ( itolizumab , trastuzumab emtansine ) received their first approvals , first marketing applications for three mabs ( vedolizumab , ramucirumab , obinutuzumab ) were submitted to regulatory agencies , and five mabs ( brodalumab , mabp1 , moxetumomab pasudotox , tildrakizumab , rilotumumab ) entered their first phase 3 studies . the current total of commercially - sponsored antibody therapeutics undergoing evaluation in late - stage studies is 30 . \n recently announced study results for farletuzumab , naptumomab estafenatox , and tabalumab indicate that clinical endpoints were not met in some phase 3 studies of these product candidates .", "id": 283} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe annual frequency of drug shortages increased 200% from 2006 to 2010 . furthermore , in 2012 the food and drug administration ( fda ) reported a record number of 251 drugs on shortage .\nthe increasing problem of drug shortages has the potential to adversely affect patient care , delay medical procedures , result in medication errors , and burden the health care system with additional costs [ 35 ] .\nwhen these medications are unavailable , it may lead to significant patient harm when clinicians must resort to second- or third - line agents that may have inferior or less evidence for use .\nthis is especially true for shortages of often non - interchangeable , curative therapies such as antimicrobials and oncologic agents , which comprise the majority of shortages .\na 2013 survey of infectious disease physicians found that 78% ( n = 489 ) of respondents had to modify their choices of antimicrobial therapy because of a drug shortage in the previous 2 years .\npoor patient outcomes due to a shortage were reported by 55% ( n = 345 ) of responding physicians who reported having to use alternative agents which were less effective , more toxic , or more costly .\nthe growing magnitude of drug shortages and the risk of patient harm they pose have gained much attention from the government , media , and researchers as strategies are developed to mitigate their effects . while progress has been made on quantifying the magnitude and causes of drug shortages , a lack of data exists on the causality of shortages on patient outcomes as well as the development of a system for reporting and monitoring patient harm on a real - time basis .\nthere remains a need for appropriate tracking of the relationship between drug shortages and patient outcomes in the long term [ 1 , 4 ] .\nspecifically , the need remains for a system where clinicians can report specific instances of patient harm they believe to be due to a drug shortage .\ntraditionally , adverse event reporting is managed through the adverse events reporting system ( aers ) of the fda ; however , aers is known to under - represent actual events due to infrequent clinician reporting .\nfurthermore , drug shortages that lead to patient harm may not be recognized as adverse events .\nwe have suggested that a novel method for maximizing the reporting of adverse events due to drug shortages would be simple , anonymous , use standardized terminology for easy tabulation , and have a mechanism for attributing causality of the adverse event to a drug shortage [ 1 , 4 ] .\nwe focused on shortages of antimicrobial drugs as they are often non - interchangeable , curative , and represent a large portion of overall shortages , thus making them particularly sensitive to shortages that result in patient harm .\nwe hypothesized that a novel method for reporting patient harm due to antimicrobial shortages would aid in anonymous and convenient reporting of these cases of patient harm .\nclinicians were asked anonymously to report occurrences of patient harm related to antimicrobial drug shortages through an online survey ( surveymonkey ; surveymonkey , palo alto , ca , usa ) consisting of 11 questions ( table 1 ) .\nthe survey was distributed through an editorial in pharmacotherapy , a letter in the american journal of health - system pharmacy , and through the american college of clinical pharmacy ( accp ) infectious diseases practice and research network ( i d prn ) email listserv .\nreports from the survey were tabulated from august 2012 through october 2013 , and three reminder emails were sent to the accp i d prn during this timeframe .\nthis study was approved as exempt by the midwestern university institutional review board.table 1survey questions1please list the full name of your institution ( for de - duplicating purposes)2how many inpatient beds does your institution currently have?3which of the following best describes the location of your institution ? \nif yes , please list the patient s age5sex : male or female6which antimicrobial was unavailable for your patient?7please list the infection for which treatment or prophylaxis was needed8what adverse event did your patient experience?9please attribute the causality of the shortage to the adverse event that occurred in your patient unrelated : the adverse event is clearly not related to the shortage unlikely : the adverse event is doubtfully related to the shortage possible : the adverse event may be related to the shortage probable : the adverse event is likely related to the shortage10please attribute a severity to the adverse event that occurred in your patient death disabling hospitalization life threatening required intervention other ( please specify)11what was the final patient outcome ?\nplease check all that apply death treatment failure / development of resistance readmission due to treatment failure increased length of hospitalization patient transferred to an institution with a supply of antimicrobial delay of therapy suboptimal treatment other ( please specify ) respondents were surveyed regarding : institution ( for de - duplication purposes ) , patient age ( if < 90 years old ) , sex , antimicrobial on shortage , type of infection requiring treatment or prophylaxis , adverse event , and patient outcome .\ncriteria for causality attribution were obtained from the common terminology criteria for adverse events ( ctcae ) of the national cancer institute . using these criteria\n, the reporter assessed the relationship between the adverse event and the antimicrobial shortage as unrelated ( clearly not related ) , unlikely ( doubtfully related ) , possible ( may be related ) , or probable ( likely related ) .\nthe severity of the adverse event was also assessed using standardized aers criteria , modified for the setting of infectious diseases . using these criteria , the reporter classified the severity of the adverse event according to the following terminology : death , treatment failure or development of antibiotic resistance , readmission due to treatment failure , increased length of hospital stay , patient transfer to an institution with a supply of antimicrobial , delay of active therapy , canceled care , or other .\noverall , there were seven de - duplicated reports of adverse events related to antimicrobial shortages .\nthe incomplete reports did not provide the level of causality due to a shortage but did report an instance of patient harm .\nall institutions were in urban settings with 500740 beds ( n = 3 ) or 100249 beds ( n = 1 ) .\nthe infections for which these patients were being treated or receiving prophylaxis included stenotrophomonas maltophilia bacteremia , pneumocystis jirovecii pneumonia , neonatal sepsis of unknown etiology , and cytomegalovirus colitis .\nfinal patient outcomes included death , delay of therapy , readmission , and limited access to treatment .\ntwo adverse events ( a delay in treatment and an inability to treat with other antimicrobials due to resistance ) were attributed to have probable causality due to a shortage , while the remaining adverse events ( death and an inability to tolerate high oral doses ) were attributed to have unlikely and possible causalities due to a shortage , respectively .\nthe antimicrobials on shortage in the incomplete reports included three cases of a shortage of sulfamethoxazole trimethoprim .\nthe infections for which these patients were being treated or receiving prophylaxis were p. jirovecii pneumonia and stenotrophomonas spp.table 2patient vignettes of complete reports detailing adverse drug events due to antimicrobial shortagespatientage ( sex)antimicrobial on shortageinfection being treatedade experiencedcausality due to shortageseverity of adefinal patient outcome1<90 ( f)sulfamethoxazole trimethoprim iv \n stenotrophomonas maltophilia bacteremiadeathunlikelydeathdeath245 ( f)sulfamethoxazole - trimethoprim ivpcp pneumonianausea / vomiting / diarrhea when given high oral dosepossiblerequired interventiondelay of therapy3<90 ( f)gentamicinempiric neonatal sepsis1 h delay of treatmentprobablerequired interventionreadmission425 ( m)foscarnetcmv colitisuntreatable due to resistanceprobableother : disease still presentother : obtained foscarnet outside the united states \n ade adverse drug event , cmv cytomegalovirus , f female , iv intravenous , m male , pcp \n pneumocystis jirovecii pneumonia patient vignettes of complete reports detailing adverse drug events due to antimicrobial shortages \n ade adverse drug event , cmv cytomegalovirus , f female , iv intravenous , m male , pcp \n pneumocystis jirovecii pneumonia\nthe methodology demonstrated in this study illustrates a successful system capable of capturing real - time instances of patient harm and attributing the causality of that harm to antimicrobial shortages . by maintaining a database where the specialists most likely to manage shortages can continuously report instances of patient harm anonymously and conveniently ,\nwe believe our methodology offers an ability to capture harmful effects of antimicrobial drug shortages on patient outcomes .\nclinicians wishing to report on future harms due to antimicrobial shortages can do so at : http://www.surveymonkey.com/s/antimicrobialshortages .\nthe instances of patient harm reported in this study further underline the harmful effects of drug shortages reported elsewhere in the literature .\nthese effects include utilization of less effective or more toxic alternative medications , medical errors , delays in procedures , and higher healthcare costs [ 35 ] .\nfor example , two of the drugs on shortage reported in our survey are first - line agents for their respective indications ( i.e. , sulfamethoxazole trimethoprim for p. jirovecii pneumonia prophylaxis , and foscarnet for cytomegalovirus colitis ) .\nit is worth noting that two of the three antimicrobials reported to be on shortage in our survey required clinicians to follow special instructions to obtain a supply .\ntrimethoprim was available through drop shipments from the manufacturer only after the need for therapy was documented to the manufacturer .\nas there may be significant time lags associated with obtaining such products , special measures are required to ensure ready access to the product at the time of need . of further note ,\nthe number of full - time equivalents allocated to shortage management has increased in many healthcare institutions ; this has not seemed to curb the inability of some institutions to procure drugs on shortage .\none potential solution may be increased education about procuring drugs on shortage and how best to mitigate their harmful effects , which antimicrobial stewardship programs could potentially provide .\nthis survey methodology , a quick and anonymous online survey , offers an advantageous alternative over conventional surveys which may only provide a snapshot of the incidence of patient harm and not specific patient characteristics .\nthe benefits of the fda aers system include that it is a publically available system for reporting adverse events and it provides a form that prompts reporters for pertinent information . however , due to issues such as prescriber disinclination to report for fear of identification and litigation , lack of time to submit reports , and lack of knowledge of the reporting structure , most adverse drug events are never reported .\nit has been estimated that under - reporting exists over 90% of the time . specifically in regards to the aers system\n, an original study found that only 57% of prescribers were aware of aers , likely leading to reporting rates ranging from 1% to 5% .\nwe have written about the need for standardization of assessing the impact of antimicrobial shortages on patient outcomes and suggested that the traditional method of reporting adverse events is likely under - reporting the true impact due to the time required for submissions , the complexity of the system , and the personally identifying nature of the report [ 1 , 4 ]\n. a 2009 review of the determinants of under - reporting of adverse events found under - reporting to be influenced in part by a lack of suitable means to report the event in 75% ( n = 45 ) of all studies , and that the available system was considered to be too bureaucratic or not easy enough in 25% ( n = 45 ) of all studies . the methodology presented here may also be useful in assessing patient harm due to shortages in other drug classes .\nreports may have been limited as respondents may have not wished to disclose medication errors or adverse events which occurred at their institutions .\naccuracy of self - reporting is an inherent liability to which all surveys , including the fda aers database , are subject . the results from our survey were driven by large institutions in urban settings ; however , results from elsewhere in the literature clearly demonstrate that institutions of all sizes and settings are affected by shortages [ 6 , 11 ] . despite these limitations , the results of this survey provide valuable information regarding patient harm due to antimicrobial drug shortages .\nour study demonstrated a novel method for encouraging providers to report patient harm due to antimicrobial shortages .\nthis method is standardized , anonymous , convenient , and capable of de - duplicating responses .\nthis pilot study has revealed unique instances of patient harm with assessed causality attributed to antimicrobial shortages .\nsuch studies may help gage the true impact of shortages and may help guide policies aimed at allocating appropriate resources to control and prevent patient harm caused by future shortages .\nmilena m. mclaughlin , erik skoglund , zachary pentoney , and marc h. scheetz have no conflicts of interest to disclose pertaining to the subject matter of this manuscript .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .", "answer": "introductionthe number of drug shortages in the united states has increased in recent years . while some literature exists on factors that contribute to antimicrobial shortages , the need remains to accurately gage the level of patient harm incurred as a result of realized antimicrobial shortages . \n furthermore , current methods of reporting adverse drug events are known to under - report instances of patient harm . \n we sought to develop an ongoing and accurate method of reporting patient harm due to antimicrobial shortages , which was convenient , anonymous , and allowed clinicians to estimate the causality due to a shortage.methodswe distributed a public surveymonkey ( surveymonkey , palo alto , ca , usa ) link to gather information regarding institution ( for de - duplicating purposes ) , patient age , sex , antimicrobial product on shortage , type of infection requiring treatment or prophylaxis , adverse event , and patient outcome.resultsto date complete data were reported on four patients being treated for infections that included stenotrophomonas maltophilia bacteremia , pneumocystis jirovecii pneumonia , neonatal sepsis of unknown etiology , and cytomegalovirus colitis . \n antimicrobials that were unavailable to patients included sulfamethoxazole \n trimethoprim , gentamicin , and foscarnet . \n two adverse events ( a delay in treatment and an inability to treat with other antimicrobials due to resistance ) were attributed with probable causality due to a shortage , while the remaining adverse events ( death and an inability to tolerate high oral doses ) were attributed to have unlikely and possible causalities due to a shortage , respectively.conclusionthese methods encourage reports of antimicrobial shortage harms.electronic supplementary materialthe online version of this article ( doi:10.1007/s40121 - 014 - 0040-z ) contains supplementary material , which is available to authorized users .", "id": 284} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin june 2014 , a 61-year - old female was admitted to keimyung university dongsan medical center because of a severe dry cough that had lasted for over 20 days . according to her medical history ,\nshe had undergone a hysterectomy in 2005 , and the pathologic diagnosis was leiomyoma of the uterus . in 2006 ,\nchest computed tomography ( ct ) findings demonstrated multiple nodules in both lungs ( fig .\nmicroscopic examination revealed a proliferating spindle cell tumor showing relatively bland nuclei , no pleomorphism , and no mitoses .\nin addition , immunohistochemical staining analysis was positive for smooth muscle actin , desmin , vimentin , estrogen receptor ( er ) , and progesterone receptor ( pr ) , and negative for cd34 , pan - ck , and s100 proteins . the result of the pathologic study was benign leiomyoma , and the nodules were diagnosed as pulmonary benign metastasizing leiomyoma ( pbml ) .\n, the patient did not return to our outpatient clinic for follow - up . upon the patient s return ,\na posteroanterior chest x - ray showed a very large mass on the right cardiac border ( fig .\nchest ct demonstrated a 101-mm mass on the right lower lobe that compressed the posterobasal segmental bronchus ( fig .\na ct - guided needle biopsy of the huge mass revealed it to be leiomyoma .\nafter right thoracotomy , a very large mass , 100 mm in size , originating from the visceral pleura of the right lower lobe was observed ( fig .\nthe mass was in contact with the parietal and diaphragmatic pleura , but no invasion was noted . near the mass , multiple fine ,\nscattered , whitish nodules measuring less than 1 cm were found on the diaphragmatic , parietal , and visceral pleura .\nwe performed an excision of the mass in the right lower lobe and excised fine nodules from the parietal and diaphragmatic pleura for biopsy .\nintrapulmonary nodules found in the middle lobe and upper lobe were not excised , because they had not increased in size .\nthe necrotic lesion showed severe cellular atypia , frequent mitoses ( more than 15 per 10 high power fields [ hpfs ] ) , and continuity of the leiomyoma and leiomyosarcoma ( fig . 2c ) .\nimmunohistochemical staining revealed that the tumor was positive for smooth muscle actin ( sma ) , er , and pr , but negative for cd34 , pan - ck , s100 , and hmb45 ( fig .\nthe nodular lesions taken from the parietal and diaphragmatic pleura showed no malignant cells . the patient was discharged 8 days after the operation without complications .\nlarge heterogeneous hypermetabolic masses were found from the left para - aortic area to the left pelvic cavity ( fig .\n3 ) , and we diagnosed them as metastatic leiomyosarcoma . additionally , increased fluorodeoxyglucose ( fdg ) uptake was observed in the peribronchial lymph nodes , the mediastinum , and the supraclavicular lymph nodes .\ntwo months later , en - bloc resection of the retroperitoneal masses with left nephrectomy was performed , and the pathologic diagnosis was metastatic leiomyosarcoma .\nwe decided to continue observing fdg uptake in the mediastinal and peribronchial lymph nodes rather than prescribing chemotherapy , because metastasis of leiomyosarcoma to the lymph nodes is rare . a chest ct scan done 1 year after surgery demonstrated no changes in the pulmonary nodules and no recurrence of the mass .\nbenign metastasizing leiomyoma ( bml ) results from metastasis of a uterine leiomyoma ; thus , bml patients have a history of uterine leiomyoma\n. the condition may occur at any age , but occurs most often in women from 30 to 74 years old .\nbml can occur in a number of different areas of the body , including but not limited to the lungs , para - aortic lymph nodes , abdominal lymph nodes , heart , breast , liver , and esophagus .\nthe most common site of occurrence is in the lungs , in which case it is known as pbml .\nthe pathogenesis of pbml is unknown , but the most common theory is hematogenous spreading of leiomyoma during uterine surgery .\nimmunohistochemical staining of affected tissue is positive for desmin , sma , pr , and er . most cases of pbml do not require treatment , but pbml that metastasizes or increases in size does need to be treated , as it can cause respiratory failure , chest pain , or hemoptysis .\nsurgical excision is the treatment of choice , but this is only possible in cases of resectable pbml .\nin some cases of pbml that a repositive for er or pr , reducing hormone release via hysterectomy , bilateral adnexectomy , and/or hormone therapy may decrease the tumor s size .\nthe incidence of the sarcomatous transformation of benign uterine leiomyomas is only 0.1%0.8% , and is most often seen in women in their 50s .\npbml can also undergo malignant transformation ; excluding our case , just 1 case of the malignant transformation of pbml has been reported .\nradiologically , it is difficult to differentiate between normal pbml and pbml that has become malignant .\non fdg pet - ct , heterogeneous fdg uptake of the tumor may reflect necrosis within the leiomyosarcoma . in our case ,\npathologically , the current criteria used to differentiate a malignant smooth muscle tumor from a benign mass are the presence of necrosis , a high mitotic index ( > 5 mitoses seen in 50 hpfs ) , nuclear atypia , cellularity , and an ill - defined tumor border .\nhowever , in primary pulmonary leiomyosarcoma ( ppl ) , progress is slow , and metastasis of ppl occurs late in the disease process .\nif the condition is diagnosed early , wide excision with negative margins ( r0 ) is the standard treatment .\nthe 5-year survival rate in ppl patients who undergo complete resection is over 50% , and recurrence is rare .\nlymph node resections are generally not necessary because ppl rarely shows lymph node involvement . for advanced lesions , depending on the size and grade of the tumor , radiation therapy , chemotherapy , or both may be indicated as an adjuvant therapy . however , the median survival of patients with an unresectable sarcoma or metastatic disease is about 12 months .\noverall , early diagnosis and complete mass resection are vital in cases of the malignant transformation of pbml .\nhowever , preventive resection or diagnostic excisional biopsy is not recommended for all pbml patients , since the occurrence of a malignant change is extremely rare\nif there is a very large , newly developed mass that is increasing in size rapidly , or if a malignant mass is found on pet - ct , diagnostic mass resection should be considered .", "answer": "pulmonary benign metastasizing leiomyoma ( pbml ) is defined as metastasis of a leiomyoma to lung tissue . \n it was first reported in 1937 . \n p bml is known as a benign disease , but can undergo malignant transformation . only 1 case of the malignant transformation of pbml to leiomyosarcoma has been reported previously . in this report , we present a case of malignant transformation of pbml .", "id": 285} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncough is one of the most distressing symptoms in cancer patients with lung or mediastinal metastasis or due to complications of cancer treatment .\ntwenty to 42% of cough do not respond to conventional medications and are referred to as refractory cough and these are often a medical challenge .\nit shows features such as abnormal throat sensation ( laryngeal parasthesia ) , increased cough sensitivity to tussigens ( hypertussia ) , and cough triggered by nontussive stimuli such as cold or talking ( allotusia ) .\ngabapentin is known to be effective in treating neuropathic pain with central sensitization and findings from the present case predicts its effectiveness in treating refractory cancer related cough .\nit further affirms the fact that vagal neuropathy may be associated with refractory chronic cough .\na 15-year - old boy , who had previously been diagnosed with malignant spindle cell sarcoma , was referred to the department of palliative care and psycho - oncology for chronic refractory cough .\nfollowing histopathological diagnosis of spindle cell sarcoma of right lower limb in the year 2014 , he had undergone surgery followed by radiotherapy for local control . in may 2015 , he presented to the clinical oncology department with a history of persistent dry cough of 6 months duration .\na computed tomography scan of thorax [ figure 1 ] revealed a large heterogenous hypodense soft tissue mass ( 10.5 cm 10.3 cm ) in the right lower lobe with extension to the left atrium through the right inferior pulmonary vein .\nin addition , there were enlarged right paratracheal , subcarinal , and hilar lymph nodes . computed tomography scan of thorax showing the mass in the right lower lobe with extension to the left atrium through the inferior pulmonary vein the child had persistent cough for the duration of 6 months .\nthe cough intensity on a numerical rating scale ( nrs ) was 10 ( out of 10 ) .\neach bout of cough lasted for 30 s and there were 20 such bouts in a day .\ncough was severe in the morning and was triggered by activities that involved walking , talking , or exposure to the cold environment .\nhis eastern cooperative oncology group ( ecog ) performance status score at the time of presentation was 3 .\na trial of codeine phosphate started by the primary treating team did not reduce cough but instead caused excessive drowsiness and giddiness due to which he had to stop the medicines .\npatient was started on gabapentin 50 mg 3 times a day and advised to increase the dose by 50 mg every 3 days until response was obtained or the child felt drowsy ( in the latter case , the drug dose would be decreased ) .\nthe patient responded significantly well with 200 mg / day of gabapentin after 1 week without any side effects such as drowsiness or giddiness and he continues to improve .\nthere was a decrease in the cough intensity to 2 ( out of 10 on nrs ) and both cough duration and bouts ( 2/day ) .\nthe child is now able to enjoy his routine life and socialize with friends and relatives .\npatients with primary or metastatic cancer of the lung often present with distressing symptoms such as breathlessness and cough which significantly impacts their quality of life\n. there are multimodal options for treatment in cancer related cough which include corticosteroids , bronchodilators , brachytherapy , laser therapies , and opioids .\nour patient had an extensive mass crossing the mediastinum which precluded radiation to the mass as this involved significant risk to the mediastinal structures .\nopioids are commonly used in cancer patients for the management of pain , cough , and breathlessness .\nopioids act by stimulating the mu receptors in the cough centers of the brain and helps in suppressing the cough . in one study ,\nslow release morphine sulfate showed a significant improvement in the cough related quality of life as compared to placebo and this was not associated with cough reflex sensitivity which is consistent with central action of morphine .\nthe treatment , on the contrary , caused significant drowsiness and giddiness affecting his quality of life .\ncough reflex is mediated by the stimulation of the vagal primary afferent nerve distributed along the tracheobronchial tree . thus , rapidly adapting receptors of the vagal afferents are known to be evoked by mechanical stimuli and deformity in the airway epithelium , which results in cough .\nthus , an unresectable mass in the mediastinum acts as a constant source of irritation for the airway which in turn triggers cough .\nwe used gabapentin in our patient with successful control in cough intensity , duration , and frequency .\ngabapentin is a lipophilic structural analog of the neurotransmitter gamma aminobutyric acid which is proven to have a central action .\nit is known to act on the alpha 2 and delta receptor of calcium channel inhibiting the release of neurotransmitters such as substance p , a tussigenic agent , and possibly inhibits the n - methyl - d - aspartate receptors .\nrecent trials have shown the superiority of gabapentin in reducing the frequency and intensity of cough .\nperipheral cough sensitivity to capsaicin was not changed by gabapentin which proves its central effect . in the same study\n, there was a significant improvement in cough related quality of life in the gabapentin arm .\nthe common side effects of gabapentin include dizziness , fatigue , headache , and confusion which was not reported by our patient .\nthere is , thus , a need to explore the use of neuromodulatory agents in symptom conditions which are known to have a neural origin such as cough , pruritus , and hiccoughs .", "answer": "vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough . \n earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin . \n we present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures . \n the patient was successfully treated with gabapentin with reduction in the cough intensity , duration , and frequency .", "id": 286} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napproximately 24% of non - hodgkin 's lymphomas are considered to be of extranodal origin .\nprimary uterine non - hodgkin 's lymphomas are extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas .\nhowever , the diagnosis of primary uterine lymphoma is often delayed due to its low incidence and nonspecific clinical presentation .\n, we present magnetic resonance imaging ( mri ) and fluorine-18-fluorodeoxyglucose ( f - fdg ) positron emission tomography ( pet)/ct findings in a patient with primary uterine peripheral t - cell lymphoma .\na 27-year - old female was admitted to our hospital because of intermittent fever with neutropenia for 7 months .\nlaboratory tests showed decreased white blood cell count ( 1.4 10/l ; range 410 10/l ) .\nserum cancer antigen 125 was elevated ( 193 u / ml ; range < 35 u / ml ) .\nmri showed an ill - defined mass involved both the uterine corpus and cervix , resulting in diffuse enlargement of the uterus .\nthis mass showed inhomogeneous hypointensity on unenhanced t1-weighted images , hyperintensity on diffusion - weighted imaging , relative hypointensity compared to the surrounding myometrium on t2-weighted images , and lower enhancement than the surrounding myometrium on enhanced t1-weighted images ( figure 1 ) .\n, f - fdg pet / ct was performed showing intense fdg uptake in the thickened wall of the uterine corpus and cervix with suvmax of 26.9 .\nthere were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum ( figure 2 ) .\ntransverse unenhanced t1-weighted image ( a ) showed an inhomogeneous hypointense mass ( arrows ) in the uterus . corresponding transverse diffusion - weighted imaging ( b ) showed peripheral hypointensity of the mass .\nsaggital t2-weighted mr image ( c ) showed the mass ( arrows ) involved both the endomerium and myometrium , resulting in diffuse enlargement of the uterus .\nthis mass showed relative hypointensity compared to the surrounding myometrium . on transverse ( d ) , coronal ( e ) , and saggital ( f ) enhanced t1-weighted images , this mass showed lower enhancement ( arrows ) than the surrounding myometrium .\nmaximum intensity projection pet ( a ) showed intense fdg uptake of the enlarged uterus ( arrow ) and multiple hypermetabolic lymph nodes ( arrowheads ) in the pelvis and retroperitoneum .\ntransverse ct ( b , c ) , corresponding pet ( d , e ) , and fused ( f , g ) images showed intense fdg uptake in the thickened wall of the uterine corpus ( arrows ) and cervix ( arrowhead ) with suvmax of 26.9 .\nct = computed tomography , fdg = fluorodeoxyglucose , mri = magnetic resonance imaging , pet = positron emission tomography .\nmicrophotograph revealed diffuse myometrial infiltration by small round tumor cells with multifocal coagulative necrosis ( figure 3a ) .\nthe tumor cells were positive for cd2 , cd3 ( figure 3b ) , cd43 , and lat , and negative for cd19 and cd20 .\nthe imaging and pathologic findings were consistent with primary peripheral t - cell lymphoma of the uterus ( stage , ii e ) . after 3 circles of chemotherapy , a follow - up mri showed decreased thickness of the uterine wall ( figure 4 ) .\nhistopathology at higher magnification ( a , hematoxylin - eosin , original magnification 400 ) revealed diffuse myometrial infiltration by small round tumor cells .\nthe tumor cells were positive for cd3 staining ( b , original magnification 400 ) .\na follow - up enhanced t1-weighted image showed decreased thickness of the uterine wall after 3 circles of chemotherapy .\nprimary uterine non - hodgkin 's lymphomas are extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas .\nthe mean age of patients with primary uterine non - hodgkin 's lymphoma at presentation is 55 years and abnormal uterine bleeding is the most frequent complaint .\nthe combination of chemotherapy and irradiation is the most effective treatment regimen for uterine lymphomas . on mri , diffuse enlargement of the uterus , relatively homogeneous signal intensity , and multinodular growth pattern\nare helpful for diagnosing uterine lymphoma . in this case , on t2-weighted mr images , the tumor showed relative hypointensity compared to the surrounding myometrium , which may be due to the hypercellularity and less necrosis of the tumor . on diffusion - weighted imaging ,\nthe tumor showed remarkable hyperintensity indicating marked restricted diffusion of the water molecules due to the dense microstructure . on enhanced t1-weighted mr images , the tumor showed lower enhancement than the surrounding myometrium , which may be due to the minimal tumor angiogenesis and destroying of the normal uterine vessels .\nmri may be helpful for the differential diagnosis between uterine lymphoma and uterine leiomyosarcoma or abscess . unlike uterine lymphoma , hemorrhage and necrosis are common in uterine leiomyosarcoma .\ntherefore , uterine leiomyosarcoma commonly manifests as a large infiltrating myometrial mass with heterogeneous hypointensity on t1-weighted mr images , and intermediate - to - high signal intensity with central hyperintensity on t2-weighted mr images .\nuterine abscesses commonly show high - signal intensity on t2-weighted mr images , which is different from relative hypointensity of uterine lymphoma .\nfdg pet / ct may be useful for detection , staging , and treatment evaluation of uterine lymphoma .\nhigh - grade uterine lymphomas usually show intense fdg uptake , whereas the low - grade ones show lower fdg uptake . therefore , fdg pet / ct may be helpful for assessment of the tumor grade .\nthis case indicates uterine lymphoma should be included in the differential diagnosis of abnormal uterine fdg accumulation along with physiological endometrial uptake , postpartum uterus , adenomyosis , endometrial hyperplasia , leiomyoma , cervical cancer , endometrial cancer , choriocarcinoma , uterine sarcoma , and uterine metastasis . in conclusion , primary uterine non - hodgkin 's lymphoma should be taken into consideration when a uterine tumor shows large size , relative hypointensity on both t2-weighted images and enhanced t1-weighted images compared to the surrounding myometrium , and intense fdg uptake on pet / ct .\nethical approval was obtained from the ethics committee of changhai hospital , shanghai , china .\nwritten informed consent was obtained from the patient for publication of this case report and any accompanying images .", "answer": "abstractprimary uterine non - hodgkin 's lymphoma is extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas . \n imaging findings of primary uterine lymphoma have rarely been reported before . \n we present magnetic resonance imaging ( mri ) and fluorine-18-fluorodeoxyglucose ( 18f - fdg ) positron emission tomography ( pet)/ct findings in a patient with primary uterine peripheral t - cell lymphoma.a 27-year - old female presented with intermittent fever with neutropenia for 7 months . \n mri showed an ill - defined mass involved both the uterine corpus and cervix , resulting in diffuse enlargement of the uterus . \n this mass showed inhomogeneous hypointensity on unenhanced t1-weighted images , hyperintensity on diffusion - weighted imaging , relative hypointensity compared to the surrounding myometrium on t2-weighted images and lower enhancement than the surrounding myometrium on enhanced t1-weighted images . \n fdg pet / ct showed intense fdg uptake in the thickened wall of the uterine corpus and cervix with suvmax of 26.9 . \n there were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum . \n uterine curettage and ct - guided biopsy of the uterine mass revealed peripheral t - cell lymphoma . \n bone marrow biopsy revealed no evidence of lymphomatous involvement . \n the imaging and pathologic findings were consistent with primary uterine lymphoma . \n after 3 circles of chemotherapy , follow - up enhanced mri showed decreased thickness of the uterine wall.despite its rarity , primary uterine non - hodgkin 's lymphoma should be taken into consideration when a uterine tumor shows large size , relative hypointesity on both t2-weighted images and enhanced t1-weighted images compared to the surrounding myometrium , and intense fdg uptake on pet / ct . \n mri may be helpful for describing the relationship between the tumor and adjacent structures . \n fdg pet / ct may be useful for tumor detection and staging .", "id": 287} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nisotretinoin is a systemic synthetic retinoid used to treat moderate to severe nodulocystic acne vulgaris that is not responding to other therapies , as well as a number of other dermatologic diseases , including psoriasis , hidradenitis suppurativa , ichthyosis , lesions associated with lupus erythematosus , some cases of severe acne rosacea , and various skin cancers , or even adjunctive therapy for acute promyelocytic leukemia.1 among other adverse effects , isotretinoin has repeatedly been associated with depression , suicidality , and psychotic symptoms , although the link between isotretinoin use and psychiatric events remains controversial.2 remarkably , when affective psychosis and obsessive - compulsive disorder ( ocd ) occur following isotretinoin treatment , associated psychopathology is generally severe and eventually poorly responsive to conventional treatment , as highlighted by recent , large , retrospective studies.3 also , although patients suffering from bipolar disorder may be at increased risk for mood symptom exacerbations due to isotretinoin therapy , including suicidal ideation , even with a concurrent antimanic therapy,3 less is known about the risk for developing ex novo affective psychosis and antidepressant manic vulnerability when isotretinoin treatment is used during adolescence . furthermore , acne itself often occurs during adolescence , and can be eventually induced by lithium , a standard treatment for bipolar disorder , which , in turn , usually has its onset at the same age .\na 25-year - old caucasian male came to his first psychiatric consultation at the age of 23 years at the suggestion of his general practitioner due to complaints about intrusive obsessive thoughts starting about one year earlier .\nobsessive symptoms essentially consisted of self - reproachment about his ineptitude in sitting academic examinations and consequent overwhelming feelings of guilt toward his parents .\nthere were no associated physical problems , although he reported a history of severe acne vulgaris that had been successfully treated by a dermatologist with isotretinoin 10 mg / day since the age of about 16 years .\ninitial evaluation led to a diagnosis of ocd , after excluding a personal or family history for psychiatric disorders .\ndiagnosis was also made on the basis of the mini international neuropsychiatric interview4 and yale - brown obsessive - compulsive scale,5 the total score for which was 26 ( 24 indicates severe ocd ) .\nhe was prescribed fluvoxamine 100 mg / day , having agreed to the proposal of dose augmentation within the following weeks .\ntwo weeks later he had an unexpected precocious response with a marked ego - dystonic reaction , so current therapy was maintained .\nmore surprisingly , two weeks later , intrusive thoughts reappeared , now associated with loss , concomitant intractable delusions of grandeur , flight of ideas , and an increase in goal - directed activity ( eg , a sudden desire to start guitar lessons and to leave law school to become a theatrical agent ) .\na diagnosis of mixed state with psychotic features was made on the basis of a young mania rating scale6 total score of 24 ( 12 indicates mania , although mixed state assessment may be roughly estimated ) .\ntherapy was then revised , halving the antidepressant dose and adding 1200 mg / day of carbamazepine ( lithium , a neuroprotective antisuicidal drug having the potential to worsen psoriasis , and typical antipsychotic augmentation options being disregarded due to a likely lack of compliance and the patient s concerns about potential dermatologic recurrences ) . despite the proposal of cognitive behavioral therapy augmentation or other nonpharmacologic interventions , the patient refused to take advantage of any therapy likely to be free of side effects , apparently for compliance reasons . after a further month\nthe patient had a relapse of obsessive symptoms , with a substantial persistence of elation ( despite considerably high carbamazepine serum levels , usually increasing by up to 60% in case of fluvoxamine coadministration ) , so he was prescribed fluvoxamine 25 mg / day and olanzapine 5 mg / day .\ndoses were then increased every three weeks , reaching a final amount of 300 mg / day and 15 mg / day , respectively .\nboth obsessive and mood symptoms progressively remitted until almost complete resolution was observed six months later .\npatients with ocd and related disorders , eg , body dysmorphic disorder , may have excessive concern about minor variations in skin color or texture , ordinary moles , or thinning hair.7 a minority of cases , eg , some patients with severe psychotic body dysmorphic disorder and acne vulgaris , may abuse dermatologic drugs and cosmetics to inhibit normal seborrhea , as in the dorian gray syndrome ( dream of eternal youth ) , eventually increasing the risk of long - term development of other psychiatric disorders , including affective psychosis.8 on the other hand , acne , alopecia areata , atopic dermatitis , and psoriasis may be associated with psychiatric conditions such as depression and suicidal ideation , as well as with the use of some psychotropic medications , possibly suggesting a substantial immunoneuroendocrine overlap.9 nonetheless , when a psychiatric comorbidity is diagnosed , patients seeking dermatologic care may interpret a suggestion to see a psychiatrist as indicating that the dermatologist thinks they are crazy or wants to get rid of them , thereby further reducing the chance of appropriate treatment . concerning the relationship between isotretinoin and the potential for subsequent onset of psychopathology ,\npositive dechallenge and rechallenge cases have been reported , prompting physicians to look out for the onset or worsening of psychiatric symptoms , including bipolar disorder.10,13 nonetheless , the neurotoxicity of the synthetic retinoic acid analogs is supported by a considerable body of literature .\nin fact , retinoids may lead to a decrease in dopaminergic orbitofrontal functioning via their effect on the hippocampus , which modulates dopaminergic function in the medial prefrontal cortex .\nretinoic acid - induced deficits in hippocampal function may lead to a downstream effect on orbitofrontal function .\nhowever , evidence regarding the effects of retinoic acid in the serotonin pathways is controversial , although higher doses have resulted in decreased or complete loss of serotonergic neurons.1 this finding has psychiatric implications because the prefrontal dopaminergic imbalance may be closely associated with depression .\nrecent evidence from positron emission tomography studies in human subjects showed isotretinoin to be associated with a decrease in orbitofrontal metabolism , which is known to play a major role in the symptomatology of both ocd and bipolar disorder .\nin fact , the molecular components required for retinoic acid signaling are expressed in the adult brain , and the overlap of brain areas implicated in retinoic acid function , stress , and depression suggests that retinoids could play a role in affective and anxiety disorders,14 which are often comorbid . in this case , the choice of the selective serotonin reuptake inhibitor fluvoxamine was based on its proven efficacy in ocd and on its modulatory effects on -1 receptors , which might increase the antipsychotic effect of atypical antipsychotic drugs , possibly contributing to the early psychotic resolution showed by the patient described here.15,16 naturally occurring neurosteroids , as well as many psychotropic drugs , bind to -receptors , which may mediate some neuroprotective action , including mood and cognition improvement.17,18 although olanzapine and other atypical antipsychotic augmentation strategies for selective serotonin reuptake inhibitor - refractory , psychotic ocds and/or concomitant mood disorder are supported by an increasing body of literature,19,20 the choice of a single agent is often difficult.21 given their higher affinity for 5-ht2a receptors than for dopamine receptors , it has been speculated that atypical antipsychotics may induce ocd , even at low doses , due to high 5-ht2a antagonism , whereas improvement is thought to occur only at high doses in response to high dopaminergic antagonism.22 the choice of olanzapine augmentation for fluvoxamine therapy was also suggested by pharmacokinetic considerations .\nfluvoxamine increases the olanzapine plasma concentration by approximately two - fold via cyp1a2 inhibition . on the other side , the alternative strategy of adding carbamazepine ( even at low doses ) to fluvoxamine and olanzapine\nwas discounted for compliance reasons . moreover , the patient did not originally show a satisfactory response to this antiepileptic drug even at 1200 mg / day ( whereas olanzapine was indeed more effective , especially in reducing psychotic features ) .\nthere were also pharmacokinetic considerations in the decision not to add carbamazepine , because it increases the renal clearance of olanzapine by about 45% and reduces the half - life of olanzapine by about 20%.23 in this case , the unusually rapid exacerbation on antidepressants , as well as the presence of plausible iatrogenic - induced depression with flights of ideas,24 pointed to a bipolar diathesis related to previous treatment with isotretinoin , suggesting the switch to an atypical antipsychotic that is associated with a rapid positive antipsychotic response .\nindeed , antidepressant lability could occur even without any previous or current isotretinoin exposure , and it may be difficult to discriminate whether mood switches and rapid exacerbation phenomena are due to isotretinoin or not .\nit is noteworthy that the patient had no prior familial or personal predictors of bipolar disorder , including during adolescence , which is the usual age of onset .\nmoreover , in this case it is remarkable that even a considerable dose of carbamazepine was not able to prevent the mood switch . also ,\nthe use of antidepressants such as fluvoxamine in the course of mixed states is debatable , although they are apparently well established in the management of ocd symptoms .\nalthough the demonstration of a def initive causal relationship between isotretinoin use and increased risk for subsequent ocd development characterized by iatrogenic vulnerability for affective psychosis is beyond the scope of this report , the modern pathogenic concept of the vulnerability stress model25 ( with isotretinoin considered an essential stress factor ) of psychiatric disease may prompt further controlled research on this association .\nfinally , in addition to the suggestion of a relationship between isotretinoin and psychiatric disorders , this case report suggests that we should consider carefully both the course of illness and psychopharmacologic choices for patients reporting long - term use of isotretinoin during adolescence and complicated by ocd .", "answer": "isotretinoin , a drug used for moderate to severe acne , has been repeatedly associated with various psychiatric complications , although a definitive causal relationship has not been established to date . \n this case report describes a 25-year - old male who developed obsessive - compulsive disorder at the age of 23 years following isotretinoin treatment for acne ( 1020 mg / day ) since the age of 16 years . \n although standard treatment for obsessive - compulsive disorder caused mood swings , the combination of fluvoxamine 300 mg / day and olanzapine 15 mg / day significantly improves the clinical picture . \n although rare , severe adulthood psychiatric complications may occur following isotretinoin treatment , requiring management which is individually tailored to the patient .", "id": 288} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncolloidal iv vi semiconductor nanocrystals ( also known as quantum dots , qds ) are of increasing potential applications in telecommunication , photoelectronic device , and biomedical labeling , etc .\npbse qds are important materials because of the strong confinement effect due to their large bohr radius and the small band gap in near infrared region .\nseveral approaches have been developed to prepare pbse qds with uniform size and high quantum yields [ 3 - 5 ] .\npbse / pbs and pbse / sio2 core / shell structures have been synthesized to stabilize pbse qds .\nbut cdse should be a better shell material due to the higher stability under air condition , the lower lattice mismatch of ~1% , and the little change of the surface chemistry and physics .\nit is difficult to grow cdse shells upon pbse cores using typical cadmium oleate anion precursor because of high reaction temperatures needed .\nhollingsworth s group recently developed a method of ion exchange to form pbse / cdse core / shell structures in which cd atoms replaced pb atoms in the outlayers of large pbse qds .\nhowever , it may not be easy to control the thickness of the cdse layers . in this work , we employed the successive ion layer adsorption and reaction ( silar ) technology to form air - stable pbse / cdse qds with strong photoluminescence\ntwo solutions were prepared for cdse shell growth . a cadmium injection solution ( 0.04 m )\nwas prepared by heating cadmium cyclohexanebutyrate ( 0.1804 g ) in oleyamine ( 8.130 g ) at 60c under n2 flow to obtain a clear colorless solution . a selenium injection solution ( 0.04 m )\nwas prepared by mixing selenium powder ( 0.0316 g ) in octadecene ( 7.880 g ) at 220c under n2 flow until a clear yellow solution was obtained .\n, pbse qds ( 4.8 nm in diameter , 1.01 10 mmol of particles ) dispersed in 5 ml of hexanes were loaded into a 25-ml three - neck flask and mixed with 1.500 g of octadecylamine and 5.000 g of octadecene .\na mechanical pump was employed at room temperature for 30 min to remove hexanes from the flask .\nthen , the predetermined amounts of the cadmium and selenium solutions were alternatively injected into the three - neck flask drop by drop with syringes using standard air - free procedures .\ntransmission electron microscope ( tem ) was used to characterize pbse and pbse / cdse core / shell qds as shown in fig .\n1 . tem images and histograms of 4.8 nm pbse ( a , b ) and 6.2 nm pbse / cdse ( c , d ) qds .\nthe pbse and pbse / cdse qd samples shown here have narrow size distributions of 8.1% ( b ) and 6.9% ( d ) , respectively figure 2 shows the evolution of absorption and photoluminescence spectra of the pbse / cdse qds upon the series growth of three monolayers of cdse shells on the 4.8 nm pbse cores .\na consistent red shift of the peak wavelength was observed in both the absorption and pl spectra .\nthe red shifts of the first excitonic absorption peak for three layers were 11 , 10 , and 11 nm , respectively .\nthe red shift of absorption and pl spectra depends on several factors including ( 1 ) the connection between pbse and cdse renders the expansion of the carriers wavefunctions out of the core region with different expansion probabilities resulting in the increase of exciton distance and ( 2 ) the surface polarization due to the different dielectric constants of pbse and cdse materials . absorption ( a ) and photoluminescence ( b ) spectra recorded during cdse shell growth . a consistent red shift of the peak wavelength ( 11 , 10 , 11 nm ) was observed when one to three monolayers of cdse shells grown on 4.8 nm pbse cores the optical gap ( egap ) of pbse qds is the minimum energy needed to excite an electron from the valence band to the conduction band .\nthe optical gap is given by where are bulk material kinetic energies of the electron and hole , respectively ; is band gap of bulk material ; are the confinement kinetic energies of electron and hole , respectively ; are the surface - polarization energies of the electron and hole , respectively ; and jeh is the direct electron \nthe size of the pbse qds ( 4.8 nm ) is much smaller than the bohr radius ( 46 nm ) ; therefore , in the strong confinement realm , the energy difference between the electron and hole should be as followed where r is the radius of quantum dot particle ; and mr is the reduced mass of the electron and hole .\nthe energy of coulomb attraction is given by where are the wavefunctions of the electron and hole , respectively ; and is the potential function of the electron and hole .\nthe surface - polarization energies of the electron and hole are where is the surface polarization potential where is the screened coulomb potential of the qd at point due to a point charge located at and is the same quantity in the corresponding bulk material system .\nwhen two semiconductors contact , both electron and hole will induce tunnelling effect and the wavefunctions will diffuse into cdse shells .\nthe transmission coefficient can be given as where e is energy barrier at the interface of core / shell structure ; m is the effective mass of diffusing particle ; a is the thickness of energy barrier . because the wavefunctions diffuse into shells , the confinement energy will change with the increase in shell thickness . according to eq .\n2 , where t is the difference of transmission coefficients of electron and hole . from the energy levels shown in fig .\n3[16 - 18 ] , the expansion probability of electron is bigger than that of hole because of the lower barriers of electron according to the very closed effective masses of electron and hole ( me = 0.070 , mh = 0.068 ) . in this case\n, one nanometer shell barrier will result in a decrease in 17.55 mev for the confinement energy .\nwe have also calculated that the increase in coulomb energy is 0.068 mev for one nanometer barrier .\ncorrespondingly , the red shifts of the first excitonic absorption peak for three individual monolayer cdse shells are counted as 10.81 , 9.45 , and 8.36 nm , respectively .\nthey are in good agreement for the experimental data taking account of the effect of surface polarization energy .\nlumo and homo structures for 4.8 nm pbse qds and 0.35 nm cdse shell the third term in eq .\n1 is the surface - polarization energy that affects the gap energy egap , which is the stark effect .\na certain number of defect states are expected on the surface of unpassivated pbse qds .\ntherefore , charge carriers trapped on or near the surface of qds may generate localized electric fields , where delocalized exciton states within the qds can be highly polarizable .\nthe surface polarization energy versus local electric field is given by where and are the resolved exciton dipole and polarizability , respectively .\naccording to muller et al.s work , the spectrum shift of cdse nanorods depends on the direction of the external electric field .\nthe positive electric field induces red shift , and the negative one leads to blue shift .\nsince the qds in this work are spherical ( zero dimensional ) , it is reasonable that their peak shifts are independent of the direction of the electric field .\nboth positive and negative electric field can cause the emission peak to red shift , and the red shift increases when the electric field is stronger .\nit has been known that unpassivated pbse qds surface is a pb atom - rich shell .\ntherefore , there may be polarization charges on the surface of pbse qds which generate surface - polarization energy .\nhowever , the polarization charges are neutralized , because pb atoms on the surface of pbse qds connect to oleic acid ( the organic ligand used in the synthesis ) .\nwhen the pbse / cdse core / shell was synthesized , cdse contacted with pb atoms instead of oleic acid ; this induced the increase of surface polarization charges .\nthe spectra shift to red because of the enhancement of the stark effect ( fig .\ndifferent crystal lattices and thermal expansivities for pbse and cdse will more or less induce surface defects at the interface of the two materials . the carriers will be trapped and result in the enhancement of the stark effect .\nsuch local fields cause the first exciton peak to shift to red and suppress the emission strength due to a reduced electron hole wavefunction overlap .\nunbalanced charges may also decrease the photoluminescence efficiency ( quantum yield ) via nonradiative auger recombination .\nthe new traps were induced by surface defects depend on the shell growth . compared with the photoluminescence of one monolayer core / shell qds ,\nhowever , it was found that more shell layers resulted in a decrease in photoluminescence strength ( fig .\nthat is also because the tensile change at the interface is nonlinear with the shell thickness .\nwhen pbse qds were covered with two layers of cdse , the good lattice tensility at the interface reduced the lattice mismatch and therefore increased the photoluminescence strength .\nwhen pbse qds were covered by three layers of cdse , the lattice tensility was stronger and hence the photoluminescence strength decreased .\neven so the quantum yield was still as high as 70% for our pbse / cdse core / shell qds ( ir-26 as the reference ) .\npbse qds are unstable even under the ambient conditions ( room temperature and room light in air ) ( fig .\nthis process for each particle induces the effective particle size decrease and the blue shift of the spectrum .\nwhen the old oxidized surface is gone , the new surface will be oxidized quickly . for pbse\n/ cdse core / shell structures , cdse shells effectively prevent pbse cores from the quick oxidation .\nthe lifetime of pbse qds under ambient conditions therefore can be extended from a few days to at least a month ( currently available data ) .\nthe stability of pbse ( a ) and pbse / cdse ( b ) qds .\nthe cdse shells prevent pbse core from the destructive oxidation . compared with the unstable pbse core ,\nthe pbse / cdse qds remained unchanged in conclusion , pbse / cdse core / shell qds with a quantum yield of 70% were synthesized .\nthe surface polarization and the expansion of carriers wavefunctions contributed to the spectral red shift .\nthe spectra red shifts during the formation of cdse shells were calculated , and they exhibited a good fit to the experimental data .\nthe funding supports from the state key laboratory on integrated optoelectronics , college of electronic science and engineering , jilin university , the worcester polytechnic institute , and the national 863 projects of china ( 2007aa03z112 , 2007aa06z112 ) are acknowledged .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .", "answer": "pbse / cdse core / shell nanocrystals with quantum yield of 70% were obtained by the successive ion layer adsorption and reaction technology in solution . \n the thickness of the cdse shell was exactly controlled . \n a series of spectral red shifts with the cdse shell growth were observed , which was attributed to the combined effect of the surface polarization and the expansion of carriers wavefunctions . \n the stability of pbse nanocrystals was tremendously improved with cdse shells .", "id": 289} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n interhemispheric connections are essential components of the complex neural network in eutherian animals [ 1 , 2 ] . among such connections ,\nthe corpus callosum ( cc ) is the most prominent commissural connection , composed of callosal axons , in the brain . in humans ,\nthe corpus callosum consists of about 200 million axons , making it the most prominent fiber tract within the central nervous system [ 3 , 4 ] .\nmany studies have clarified the molecular mechanism involved in the development of the cc in humans using mouse experiments . \ncallosal neurons are mostly found in layers ii / iii and layer v of the cerebral cortex in rodents .\nrecently , molecules related to the identities of the general or subtypes of cortical neurons have been disclosed .\nalcamo et al . reported that satb2 , a dna - binding protein , has a key role in the specification of callosal neurons and the formation of corticocortical connections . \ndevelopmentally , callosal axons from layer v first start to project to the contralateral targets , and callosal axons from the upper layers follow the preexisting axons .\nafter the callosal axons start to elongate , they are guided by many cues within their pathfinding route .\nalthough the importance of such cues in the development of callosal axons has been known for over 30 years , it still remained unclear until recently how these cues help callosal axons encountering them to project precisely to their targets .\nrecent studies have , however , revealed the detailed mechanisms in the regulation of axon guidance by these structures .\nmidline structures , which consist of glia and neurons , express or secrete short- or long - range guidance molecules . in the contralateral cortex , where the callosal axons terminate\n, interactions with postsynaptic neurons play important roles , in an activity - dependent manner , in ensuring proper projections [ 1012 ] . in this paper , we first focus on how the callosal axons are guided by the cues that they encounter , namely , the ( 1 ) midline structures and ( 2 ) neighboring axons , from the time that they start to grow until they reach their targets in the contralateral cortex . then , we describe the activity - dependent development of the interhemispheric connections .\nthe midline structures mainly consist of glial populations , but also contain neuronal populations . the role of the midline glial structures in the formation of the cc\nin the mouse brain , these glial structures have been shown to already exist on embryonic day ( e ) 15.0 and can guide the growth of callosal axons [ 8 , 14 , 15 ] .\nthe midline glial structures mainly consist of four structures : the glial wedge ( gw ) , the indusium griseum ( ig ) , the midline zipper ( mz ) , and the glial sling ( gs ) [ 8 , 16 ] ( figure 1 ) .\nthe mz is thought to be required for the fusion of the two hemispheres , which facilitates the passage of axons across the midline [ 9 , 17 ] .\nthe other structures are responsible for promoting the crossing of at least the callosal axons [ 1823 ] .\nthese structures help the callosal axons find their correct path by secreting or expressing guidance molecules .\ninterestingly , shu and richards have illustrated that correct orientation as well as the presence of the gw is required for callosal axons to turn toward the midline ; in one experiment , when the gw was replaced with 180 rotation ( medial to lateral ) , the axons turned away from the midline . \nstudies have gradually uncovered the molecules secreted by the midline structures for callosal axon guidance .\nthe axon guidance cues for callosal neurons secreted by the midline structures have been classified into two types : long range ( figures 2(a)2(c ) ) and short range ( figure 2(d ) ) .\nthe long - range guidance molecules are secreted by the midline glial populations , forming a concentration gradient and helping callosal axons pass through the cc with attractive ( figure 2(a ) ) and repulsive signals ( figures 2(b ) and 2(c ) ) .\nslits [ 15 , 24 , 25 ] , wnts , netrins [ 27 , 28 ] , draxin , and semaphorins are some of the reported long - range guidance molecules .\nhave suggested a novel role of slits in regulating the positioning and maturation of the midline glial populations , presumably independent of the activity of its receptor , robo1 , in addition to its role as a repulsive axon guidance cue . wnt5a\nnot only promotes axon outgrowth as a long - range guidance molecule , but also serves as a short - range repulsive axon guidance cue [ 32 , 33 ] . \nin addition to the midline structures , other cell populations have also recently been shown to play roles in the formation of the cc .\ngabaergic and glutamatergic neurons that transiently exist within the cc have been shown to be able to attract callosal axons .\nthe meninges have also been reported to be involved in the development of the cc .\nbmp7 secreted by the meninges has been shown to inhibit the outgrowth of callosal axons , potentially preventing early formation of the cc . \nthe short - range molecules guide axons through transmembrane or membrane - associated proteins ( figure 2(d ) ) .\neph receptors are divided into two subclasses , a and b , according to the sequence homology and binding affinity for their ligands , ephrins a and b , respectively [ 36 , 37 ] .\nalthough the ephrin / eph system signals through eph tyrosine kinase receptors , ephrins can also transduce reverse signals into the cell in which they are expressed . the ephb receptors and ephrin b ligands\nhave been well studied and shown to play important roles in callosal axon pathfinding [ 39 , 40 ] .\nimportantly , the complementary expression of multiple ephrin b ligands and ephb receptors in the callosal axons and midline structures has led to the hypothesis that interactions occur between the eph receptors in callosal axons and ephrins in the midline structures or vice versa , although it is also possible that the interactions occur between callosal axonal fibers .\nthe expression of ephrin b ligands in the callosal axons is suggestive of the involvement of reverse signaling , and bush and soriano showed that ephrin - b1 reverse signaling is critical for callosal axon pathfinding , which requires the binding of the psd-95/dlg / zo-1 ( pdz ) domain - containing proteins for the transduction of this reverse signal .\n pioneer neurons represent one of the most important players in callosal axon guidance by other preexisting axons during cc development . on e15.5 in mice , the axons of the pioneer neurons , which originate from the cingulate cortex ,\ncross the midline and enter the contralateral cortex ( figure 3(a ) ) [ 42 , 43 ] .\nit has been shown that cc genesis is triggered by these pioneer axons [ 39 , 4245 ] ; pioneer axons are the first to form the path for the commissural neurons through interactions with several cues , including the midline structures , and on e17.0 , the most early follower axons from layer v follow those of these pioneer neurons [ 42 , 43 , 46 ] ( figure 3(a ) ) .\nan accepted view is that the follower axons utilize their direct interactions with the pioneer axons to find their correct path of growth , although the molecular mechanism of such interaction remains unclear .\ninterestingly , piper et al . described the molecular mechanisms driving the guidance of the cortical pioneers during development .\nthey demonstrated that neuropilin 1 expressed on the cingulate pioneers plays a crucial role in the crossing of the midline by the pioneer \nwhile many studies have revealed the indispensable roles of the interactions between the callosal axons and the midline structures , it is still unclear whether axon - axon interactions play important roles in callosal axon pathfinding .\nalthough increasing evidence has revealed the importance of these interactions in other systems , such as the retinal , spinal and olfactory systems [ 4750 ] , the involvement of such axon - axon interactions in cc development remains to be explored in detail .\nhave recently reported repulsive interactions between callosal axons originating from the medial and lateral cerebral cortices ( figure 3(b ) ) .\nbased on a previous study by the same group , they focused on epha3 , which is preferentially expressed in the callosal axons from the lateral cerebral cortex , and found that knockdown of epha3 in the lateral cortical axons resulted in their disorganized segregation in the cc and disrupted axon pathfinding .\nthey have suggested that epha3 mediates , at least in part , the repulsive interactions between the medial and lateral cortical axons . \nso far , several studies using knockout and transgenic mice have identified molecules involved in the development of the cc . however , as knockout and transgenic mice show influences of all developmental stages , analyses of these mutant mice are not necessarily sufficient for describing the primary causes of the abnormal phenotypes .\nrecent studies using in utero electroporation and various culture experiments , including the stripe assay [ 37 , 54 , 55 ] , have enabled reasonably easy analysis of each specific stage of cc development .\nfurther experiments focusing on each step of development will be essential to understand the entire process of formation of the cc .\nto eventually establish interhemispheric connections through the cc , reshaping of the axons is also crucial .\nthe callosal connections are initially exuberant and brushed up by the selective death of neurons and withdrawal and degeneration of axonal collaterals . since callosal axons start to establish synapses with specific postsynaptic neurons after entering the contralateral hemisphere [ 39 , 57 ] , the involvement of synaptic activity - dependent mechanisms ( as well as nonsynaptic activities ) in this process of reshaping of the axons has been shown by many studies [ 57 , 58 ] . in the visual system , for example , the stimuli from the eyes contribute to the formation of the precise patterns of callosal axonal connections [ 59 , 60 ] . \nimportantly , although the callosal axons are generally believed to have a simple mirror projection across the cc in the contralateral hemisphere , there are also heterotopic callosal projections . in addition\n, the tangential distribution of the callosal axon projections is not even in the adult cortex .\nfor example , the callosal connections are highly focused at the level of the primary areas .\nwhile these might possibly be established during the later development of the callosal axon projections ( i.e. , refinement and elimination ) , establishment of such uneven projections in the early phase of development can not also be ruled out .\nrecently , synaptic and non - synaptic activities have also been reported to be involved in the regulation of different aspects of development of the callosal projections besides reshaping of the axons .\nblockade of the spontaneous electrical activity of the callosal neurons resulted in abnormal projections in the somatosensory cortex and visual cortex .\ninterestingly , blockade of the spontaneous electrical activity of projection neurons such as the motor and olfactory neurons also influenced a variety of guidance and adhesion molecules that are critical for their development [ 6163 ] , suggesting that spontaneous electrical activity of the axons may also have some role in axon guidance .\n as described above , a number of different control mechanisms are involved in the development of the interhemispheric connections , and disruption of any of these mechanisms may cause malformations of the cc .\nsome examples are knockout mice lacking some of the molecules involved in the formation of the midline glial structures [ 1923 ] , gabaergic neurons [ 34 , 64 , 65 ] or pioneer neurons , or the axon guidance mechanism\n. phenotypes of such knockout mice are quite varied and range from hypoplasia or partial dysgenesis of the cc to complete dysgenesis and formation of probst 's bundles [ 40 , 67 ] , which are also observed in partial dysgenesis . \na comparison between mice and humans revealed many similarities in the development of the cc between the mouse brain and human brain .\nnot only are the midline glial structures conserved in humans , but also the expression profiles of the molecules known to be involved in the formation of the cc are similar between human and mouse brains [ 9 , 69 , 70 ] . in humans , several psychiatric , neurologic , and metabolic disorders have been shown to be associated with congenital agenesis of the cc or the surgical procedure , callosotomy [ 5 , 71 , 72 ] . among the famous of these reports is the story of the patient with callosotomy who could not verbally describe the stimulation presented to his freshly disconnected right hemisphere . in subjects with complete dysgenesis of the corpus callosum ,\npaul et al . described that despite having normal iq , individuals with complete dysgenesis of the cc show impaired social intelligence , analyzing their responses to pictures from the thematic apperception test .\nmoreover , many studies have reported that major mental disorders , such as autism , attention deficit hyperactivity disorder ( adhd ) , and schizophrenia , may be related to the morphology of the cc [ 7476 ] .\nhowever , the precise nature of these associations remains unclear . how could malformations of the cc have any relation to these disorders ? do the genes associated with these disorders play a role in normal cc development ?\nfuture studies on the development of the cc may help elucidate the precise nature of these associations .\n by integrating information between the right / left hemispheres , interhemispheric connections enable us to accomplish higher brain functions .\ndevelopment of interhemispheric connections such as the cc is guided by molecules in the axonal environment , under the regulation of a number of different control mechanisms .\nit would be of great interest to conduct detailed investigation of the mechanisms underlying cc development , especially in view of their relevance in the pathogenesis of human disorders .", "answer": "numerous studies have investigated the formation of interhemispheric connections which are involved in high - ordered functions of the cerebral cortex in eutherian animals , including humans . \n the development of callosal axons , which transfer and integrate information between the right / left hemispheres and represent the most prominent commissural system , must be strictly regulated . from the beginning of their growth , until reaching their targets in the contralateral cortex , the callosal axons are guided mainly by two environmental cues : ( 1 ) the midline structures and ( 2 ) neighboring ? \n axons . \n recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms . in this paper , we review these guidance mechanisms during the development of the callosal neurons . \n midline populations express and secrete guidance molecules , and pioneer \n axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons . \n finally , we describe callosal dysgenesis in humans and mice , that results from a disruption of these navigational mechanisms .", "id": 290} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan hiv - negative male , in his sixties , originally presented with a 6-month history of an isolated large nodule on the right malleolar region which was confirmed as kaposi 's sarcoma ( ks ) on excision .\nsubsequently he continued to develop more papules and plaques on the feet and over the following 7 years underwent excision of around 20 skin lesions under local anaesthesia .\nmore recently he developed , simultaneously , a crop of 5 nodules and a large plaque of ks 5.5 cm in diameter on the dorsum of the right foot with extension to the interdigital spaces and toes ( fig . 1a , fig .\nchemotherapy with intravenous liposome - encapsulated doxorubicin was not considered because of the significant comorbidities including mild to moderate heart failure .\ntherefore , in the following order , we tried two courses of photodynamic therapy , imiquimod 5% cream applied once daily for 8 weeks and a cycle of anti - herpes therapy based on valganciclovir .\nit was decided to administer intralesional vinblastine 1 mg / ml diluted 1:5 with saline solution . however , the patient developed side effects such as general malaise , swelling and erythema of the perioral and periocular areas and tingly tongue after the first injection , in keeping with a possible allergic reaction .\nat that point , at a bit of a loss for options , we switched to doxorubicin . following a serial dilution test from 1:20 to undiluted ,\nthis medication was used intradermally at the dose of 2 mg / ml diluted 1:1 with saline solution . the large ks plaque on the dorsum of the right foot\nwas treated by spacing the intradermal injections every 5 mm , using a similar technique to that used in the treatment of axillary hyperhidrosis with botulinum a toxin .\nthe treatment led to complete resolution of the ks lesions after 4 treatments spaced 6 weeks apart .\nwe observed skin necrosis in some well - delimited areas following each injection ( fig .\n1b ) , associated with mild to moderate pain which was well controlled with paracetamol 1,000 mg twice daily .\nthe patient has not developed any new lesions for almost 18 months and continues to remain clear ( fig .\nks is an angioproliferative disease associated with human herpesvirus 8 . the classic variant of ks is characterised by a low mortality and significant morbidity , and treatment needs to be finely balanced between these two aspects . to date\n, a curative treatment has yet to be found and therapeutic management includes surgery , radiotherapy , chemotherapy or a combination of all of the above .\nalthough in recent years numerous agents such as thalidomide , imatinib , sirolimus as well as matrix metalloproteinase inhibitors ( col-3 ) , anti - angiogenic factors ( bevacizumab ) and nf-b inhibitors ( bortezomib ) have been tried , the outcome of these treatments remains unsatisfactory .\nliposomal anthracyclines ( pegylated or liposomal daunorubicin or doxorubicin ) and taxanes such as paclitaxel therefore remain the cornerstones of systemic therapy against ks .\ndoxorubicin acts through intercalation of double - stranded dna bases and by inhibiting dna topoisomerase ii whose activity is markedly increased in proliferating cells .\nit represents a particularly effective treatment for widespread ks as it accumulates in highly vascularised lesions .\ncommon agents for intralesional use in ks include interferon alpha , and more recently vincristine and vinblastine .\nalthough intralesional doxorubicin is a standard treatment for ks in some centres , there are no publications showing the effectiveness of this treatment in ks .\nintralesional doxorubicin was very successful in this case and the persistent remission induced would suggest that doxorubicin might be equally or even more effective than other standard intralesional treatments for ks cutaneous lesions in selected cases . further studies with a large cohort of patients could be helpful to clarify the impact of intralesional doxorubicin in ks .", "answer": "classic kaposi 's sarcoma ( ks ) is a disease with low mortality but high morbidity . \n the optimum treatment of ks depends upon several factors , including location of lesions , disease progression , severity of symptoms and patient preference . \n we report the long - term response to the use of intralesional doxorubicin to successfully treat a large cutaneous lesion of ks on a patient refractory to traditional treatments .", "id": 291} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nexperimental groups of 20 ( 4- to 6-week old ) c57bl/6 female mice ( charles river , l'arbresle , france ) were injected intracerebrally with 20 l of 10% ( weight / volume ) homogenates per mouse prepared from brain stem samples of 3 cattle tse isolates .\ntwo of the isolates were characterized , as previously described ( 7 ) , by a higher molecular mass of unglycosylated prp ( h - type isolates ) and labeling with p4 monoclonal antibody ( table ) .\nmice were housed and cared for in an appropriate biohazard prevention area ( a3 ) according to european ( directive 86/609/eec ) and french ethical committee ( decree 87848 ) guidelines .\nmice were checked at least weekly for neurologic clinical signs and were killed when they exhibited signs of distress or confirmed evolution of clinical signs .\nthe whole brain of every second mouse was frozen and stored at 80c before western blot analysis .\nfrozen mouse brain tissues and fixed brain tissues were examined by western blot analysis and immunohistochemical tests as previously described ( 12,13 ) .\nprp extracted from half of whole brain was detected with monoclonal antibodies sha31 ( 1:10 from tesee sheep / goat western blot , bio - rad , hercules , ca , usa ) ( 14 ) and 12b2 ( 340 ng / ml ) ( 15 ) . these antibodies are directed against the 144-wedryyre-151 and 88-wgqgg-92 murine amino acid prp sequences , respectively .\nantibody 12b2 , which has an n - terminal specificity similar to that of monoclonal antibody p4 , shows poor binding to bse - derived prp , but unlike p4 , binds with high affinity to prion protein from most mammalian species , including mice and cattle .\nbound antibodies were detected by using enhanced enzymatic chemiluminescence ( amersham , little chalfont , uk ) or supersignal ( pierce , rockford , il , usa ) and visualized either on film ( biomax , eastman kodak , rochester , ny , usa ) or directly in an image analysis system ( versadoc , bio - rad ) .\nmolecular masses of prp glycoforms were determined as the average of the center positions of the bands from at least 3 repeated electrophoretic procedures , as measured by comparison with a biotinylated marker ( b2787 , sigma , saint louis , mo , usa ) included on each gel .\nimmunologic reactivities of antibodies 12b2 and sha31 were compared in western blots run in parallel with the same samples with both antibodies .\nafter intracerebral injection of cattle brain samples into c57bl/6 mice , disease was observed in mice with the 2 h - type isolates , as well as with the bse sample .\nsurvival periods of mice and results of prp detection among mice analyzed by western blot are shown in the table .\nwestern blot analysis of prp from h - type infected mouse brains in comparison with bse - infected mice is shown in figure 1 .\nthis pattern showed higher molecular mass prp glycoforms in mice infected with h - type isolates than in mice infected with a typical bse agent ( 1.1- to 1.5-da difference in the unglycosylated prp ( figure 1a ) .\nstudies of prp protease cleavage showed that only the prp of mice infected with h - type isolates was recognized by antibody 12b2 ( figure 1b ) .\nthis finding is in contrast to the result obtained with monoclonal antibody sha31 directed against an epitope in the central region of the protein , which showed that the 12b2 epitope was preserved in h - type infected mice .\nthus , the molecular features of h - type cattle isolates , which are distinct from those of the bse agent , were maintained after development of disease in mice .\nwestern blot analysis of disease - associated prion protein ( prp ) from proteinase k treated brain homogenates of c57bl/6 mice infected with type h ( lanes 2 and 4 ) or bovine spongiform encephalopathy isolates ( lanes 3 and 5 ) .\nprp of mice infected with an experimental scrapie strain ( c506m3 ) ( 6 ) was used as a control ( lane 1 ) .\nmonoclonal antibodies used for detection of prp were sha31 in panel a and 12b2 in panel b. lane m , molecular mass markers : 39.8 , 29 , 20.1 , and 14.3 kda .\nhistopathologic analysis showed vacuolar lesions in the thalamus ( figure 2a ) that were absent from the hypothalamus , cochlear nucleus , and superior collicules .\nthese 3 neuroanatomic sites were severely affected in c57bl/6 mice brain after primary passage of the bse agent as we and others have reported ( 1 ) .\nabnormal prp was detected only in amyloid plaques ( figure 2b ) , in contrast to what was reported after bse transmission in c57bl/6 mice ( 1 ) .\na ) characteristic vacuolar lesions in the thalamus ( hematoxylin and eosin stained , scale bar = 60 m ) .\nb ) immunohistochemical analysis of prion protein with monoclonal antibody 12b2 ( diluted 1:200 ) shows the absence of granular deposition , but the presence of plaques in the thalamus .\nthe inset shows that plaques are amyloids since they bind congo red and show birefringence in polarized light ( scale bar = 60 m , scale bar in inset = 16 m ) .\nour data show that the recently identified bovine h - type isolates involve an infectious agent that can induce development of a disease across a species barrier , while maintaining the specific associated prp molecular signature .\nthis evidence in favor of a new bovine prion strain in cattle suggests that bse is not the only transmissible prion disease in cattle .\nthese cases suggest either the existence of alternative origins of such diseases in cattle or phenotypic changes of prp after infection with the bse agent .\nhowever , based on analysis of molecular features of prion diseases in cattle , this situation is similar to that in humans ( 5 ) , in which different subtypes of sporadic creutzfeldt - jakob disease agents are found .", "answer": "we previously reported that cattle were affected by a prion disorder that differed from bovine spongiform encephalopathy ( bse ) by showing distinct molecular features of disease - associated protease - resistant prion protein ( prpres ) . \n we show that intracerebral injection of such isolates into c57bl/6 mice produces a disease with preservation of prpres molecular features distinct from bse .", "id": 292} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbreast cancer screening programmes are now an established part of the health care service of many countries . the continuous evaluation of this practice is based on observational studies , leading to the possibility of confounding and self - selection bias .\nto assess the effect of screening , breast cancer mortality in both screened and not screened women has to be compared ; this can be looked upon as the relative risk ( rr , or rate ratio ) of breast cancer mortality .\nconfounding bias of the rr occurs when the prevalence of a risk factor ( or set of risk factors ) for breast cancer death is imbalanced across the compared groups . to adjust for the confounding effect\n, the prevalence of the risk factor(s ) has to become similar in both groups .\nusually age is the only risk factor measured when evaluating population - based breast cancer screening programmes , because information on date of birth and date of invitation of women is mostly available .\nthis term covers both within - stratum confounding , for example too - broad age categories , and confounding due to unmeasured variables .\nself - selection bias can be regarded as a special form of residual confounding because participation may induce an imbalance in the risk factors for breast cancer death .\nhaving accounted for age , we clarified the influence of adjustment for residual confounding on the rate ratio of breast cancer death .\nwe compared the mortality rate in the screened ( ms ) with not screened women ( mns ) .\nthis results in an apparent screening mortality association ( rra ) that is seemingly real , but not necessarily so because of possible residual confounding bias .\nspecific screening effect rrs , and a non - specific effect of the potential confounding factor(s ) c , which is reflected in the following formula . \n\n\\documentclass[12pt]{minimal } \n\t\t\t\t \\usepackage{amsmath } \n\t\t\t\t \\usepackage{wasysym } \n\t\t\t\t \\usepackage{amsfonts } \n\t\t\t\t \\usepackage{amssymb } \n\t\t\t\t \\usepackage{amsbsy } \n\t\t\t\t \\usepackage{mathrsfs } \n\t\t\t\t \\usepackage{upgreek } \n\t\t\t\t \\setlength{\\oddsidemargin}{-69pt } \n\t\t\t\t \\begin{document}$$ \\begin{aligned } { \\text{rr}}_{\\text{a } } & = { \\text{m}}_{\\text{s } } /{\\text{m}}_{\\text{ns } } \\\\ & = { \\text{rr}}_{\\text{s } } * { \\text{c } } \\\\ & = { \\text{rr}}_{\\text{s } } * \\left [ { { \\text{p } } _ { 1 } { \\text{rr}}_{\\text{c } } + \\left ( { 1-{\\text{p } } _ { 1 } } \\right ) } \\right]\\,/\\,\\left [ { { \\text{p } } _ { 2 } { \\text{rr}}_{\\text{c } } + \\left ( { 1-{\\text{p } } _ { 2 } } \\right ) } \\right ] \\\\\n\\end{aligned } $ $ \\end{document } the quantity c thus represents the effect of the potential confounder(s ) among screened and the not screened women .\nthe influence of c depends on the relative risk of breast cancer death rrc , the proportion p1 of screened women with the confounder present , and the proportion p2 of not screened women having the confounder .\nthe formula is based on previous work by cornfield and colleagues , schlesselman and greenland .\n, that the apparent rra is 0.50 , and a risk factor producing a twofold increase in risk of breast cancer death ( rrc ) is present among 20% ( p1 ) of the screened group and 50% ( p2 ) of the not screened group . then , the non - specific part of the apparent screening effect is 0.20 * 2 + 0.80 * 1 = 1.20 among the screened women , and 0.50 * 2 + 0.50 * 1 = 1.50 among the not screened women . the ratio of these non - specific effects is 1.2/1.5 = 0.80 , which is the influence of confounding ( c ) among the screened and not screened groups .\n1a heuristic device to address residual confounding in the mortality effect of breast cancer screening .\nboth arrows on the left indicate the observed breast cancer mortality risk in the screened and not screened group , suggesting rra = 0.50 .\nwe assume that a confounder with a twofold relative risk on breast cancer death ( rrc ) , is present among 20% ( p1 ) of the women in the screened group and among 50% ( p2 ) in the not screened group .\nthe arrow on the right indicates the expected breast cancer mortality risk in the not screened population when the presence of the risk factor in that group is adjusted from 50% to 20% .\n2 ) a heuristic device to address residual confounding in the mortality effect of breast cancer screening . both arrows on the left indicate the observed breast cancer mortality risk in the screened and not screened group , suggesting rra = 0.50 .\nwe assume that a confounder with a twofold relative risk on breast cancer death ( rrc ) , is present among 20% ( p1 ) of the women in the screened group and among 50% ( p2 ) in the not screened group .\nthe arrow on the right indicates the expected breast cancer mortality risk in the not screened population when the presence of the risk factor in that group is adjusted from 50% to 20% .\n2 ) in the above calculation we used the cohort approach and the risk ratio ( or rate ratio ) as a measure of effect .\nhowever , this same method can be applied when the odds ratio ( or ) is the effect measure .\ncontrol design has been increasingly used for the evaluation of screening programmes [ 612 ] . in the case \ncontrol evaluation , the odds of having been screened versus not screened in the case group of breast cancer deaths is compared to the same odds in the control group of invited women from whom the cases originate .\nas an example , we report on a case control study conducted within the nijmegen breast cancer screening programme which started in 1975 . after adjustment for age , we found that the breast cancer mortality rate in the screened group was 65% lower than that of the not screened group : or = 0.35 and 95% confidence interval ( ci ) = 0.190.64 .\ndense mammographic breast pattern , for which a high relative risk of 6 has been reported , is a likely candidate for being treated as a confounding factor . despite its strength ,\nnevertheless , suppose its prevalence in all screened women is 5% ( p1 = 0.05 ) in contrast to a supposed 20% ( p2 = 0.20 ) prevalence in the not screened women , then , according to the formula , the apparent or of 0.35 would be adjusted to an or of 0.56 ( see also fig . 2 , left upper diagram).fig . \n2diagrams of the adjustment for residual confounding in the effectiveness measurement of breast cancer service screening .\nmortality or = 0.35 ; panel b is for or = 0.50 and panel c for or = 0.75 . from top to bottom , the figures represent the adjusted ors for confounding factors with rrc = 6 , 4 , 2 and 1.5 , respectively .\nthe x - axis displays the proportion ( p2 ) of the not screened population with the confounding factor .\nthe lines displayed in the figures present the adjusted or for the confounding factor for p2 ranging from 0.0 to 0.6 , and four different points of departure for p1 of the screened population ( upper line at p1 = 0.05 , then p1 = 0.10 , p1 = 0.20 and the lowest line p1 = 0.35 ) .\nthe y - axis in each figure depicts the expected ors adjusted for residual confounding diagrams of the adjustment for residual confounding in the effectiveness measurement of breast cancer service screening .\npanel a shows the baseline situation of an age - adjusted screening mortality or = 0.35 ; panel b is for or = 0.50 and panel c for or = 0.75 . from top to bottom , the figures represent the adjusted ors for confounding factors with rrc = 6 , 4 , 2 and 1.5 , respectively .\nthe x - axis displays the proportion ( p2 ) of the not screened population with the confounding factor .\nthe lines displayed in the figures present the adjusted or for the confounding factor for p2 ranging from 0.0 to 0.6 , and four different points of departure for p1 of the screened population ( upper line at p1 = 0.05 , then p1 = 0.10 , p1 = 0.20 and the lowest line p1 = 0.35 ) .\nthe y - axis in each figure depicts the expected ors adjusted for residual confounding other risk factors for breast cancer like obesity , socio - economic status , nulliparity , late age at menopause , early age at menarche , and family history show a 1.5 to fourfold relative risk of breast cancer at most .\nwe assume that the risk magnitude of the factors applies to the incidence and mortality alike .\npanel a shows the baseline situation of an age - adjusted screening mortality or of 0.35 ; panel b is for or = 0.50 and panel c for or = 0.75 .\nthe expected values of the ors in order of decreasing magnitude are displayed on the y - axis in each figure : after adjustment for dense breast pattern rrc = 6 ; late age at menopause rrc = 4 ; nulliparity rrc = 2 ; and serious overweight rrc = 1.5 .\nthe x - axis shows the proportion ( p2 ) of the not screened population with the confounding factor . in each figure , the lines present the or adjusted for the confounding factor with p2 ranging from 0 to 0.6 , and four different situations of the proportion ( p1 ) confounder in the screened group : the upper line is for a p1 = 0.05 , then p1 = 0.10 , p1 = 0.20 and the lowest line for a p1 = 0.35 . in practice ,\nprevious screening programme evaluations have qualitatively discussed the magnitude of residual confounding bias on their effectiveness estimate [ 6 , 9 , 10 , 12 ] or estimated the amount of bias due to self - selection [ 7 , 8 , 11 ] .\nwe present an educated and pragmatic method to quantify the potential impact of residual confounding , and to de - bias the comparison of screened with unscreened groups , a method originally introduced by cornfield et al . .\nour results demonstrate that residual confounding has a minor influence on the observed screening effect . closely related to residual confounding\nthe difference between these three biases is subtle ; the nuances seem to lie in the clarification of definable confounding factors or a combination of indefinable confounding factors .\nself - selection into screening may result in an imbalance of a combination of indefinable risk factors , causing a different background risk of dying from breast cancer in screened versus not screened women .\nhealthy screenee bias may occur because some women in the not screened group , although invited for screening , may already have been diagnosed with cancer , while screened women were not diagnosed with breast cancer at the time of participation .\nboth biases can be regarded as a form of residual confounding since participation in screening may be correlated with the baseline risk of dying from breast cancer .\nan estimate of the amount of self - selection can be obtained by calculating the ratio of the breast cancer deaths among not invited and not screened women .\nthis calculation is not possible in a steady state situation of population based screening since there is no uninvited group . by using the implementation period of screening\n, we quantified a 0.84 lower background risk in not screened women compared with not yet invited women .\nduffy et al . proposed a factor based on data from the swedish and canadian screening trials , showing a 1.36 higher risk for not screened women . with these factors ,\nthe difference in background risk between not screened and screened women can be calculated by taking the percentage uptake in a programme into account .\nfor instance , if we use duffy s factor of 1.36 and if the screening uptake is 80% , which is in accordance with most european programmes , not screened women have a 1.42 higher background risk compared with screened women .\nthis factor actually represents c in our formula , it is the difference in background risk p1 = 0 and p2 = 1 . in this scenario an apparent or of 0.35 would be adjusted to 0.51 . however , using our factor of 0.84 , not screened women have a 0.80 lower background risk compared with screened women . in our scenario\nan apparent or of 0.35 would be adjusted to 0.28 . in cornfield s original paper\napparent effect , then rra = c , and rrs = 1 . in our example\nwe applied this method to adjust ors for combinations of p2 between 0 and 0.6 , and values of p1 = 0.05 , 0.10 , 0.20 and 0.35 .\nthese values were chosen based on the expected prevalence of the risk factors in the female population , i.e. 5% for mammographic density , 10% for late age at menopause , 20% for nulliparity , and 35% for serious overweight .\nas , we aimed to challenge the age - adjusted screening effect , we developed scenarios where p1 was smaller than p2 .\nour calculation does not account for random error or uncertainties about the relation of risk factors and breast cancer .\nit is possible to correct for this by using more complex techniques based on a monte carlo and a bayesian approach .\nhowever , the aim of this study was to present a heuristic device to address residual confounding .\nin conclusion , in studies on breast cancer screening the mortality reduction ranges from 38 to 70% [ 612 ] .\nas we have shown , residual confounding does not have a great effect on these estimates of screening effectiveness .\nafter having addressed for age , future breast cancer screening programme evaluations can ignore residual confounding .", "answer": "residual confounding , after adjustment for age , is the major criticism of observational studies on breast cancer screening effectiveness . \n we developed realistic scenarios for the prevalence and strength of risk factors on screened and not screened groups , and explored the impact of residual confounding bias . \n our results demonstrate that residual confounding bias is a minor issue in screening programme evaluations .", "id": 293} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nimproving quality of life and quality and management of care of clients with a schizophrenic disorder by the use of a comprehensive internet based disease management ( dm ) platform . presenting factors influencing the implementation of an internet based dm platform for clients with schizophrenia .\ntwo mental health care institutions in the south of the netherlands participate in the implementation of the digital instrument ( the dm platform ) .\nthe implementation of the dm platform will be followed by a process and an effect evaluation .\nmeasurement instruments : in the effect evaluation , quality of life , number of symptoms of schizophrenia , quality of care , social functioning , self management , and insight in schizophrenia and its treatment will be measured .\nprocess evaluation : semi - structured interviews will be held with different ( formal primary and secondary , and informal ) caregivers , managers and clients of each institute . these interviews will be conducted before the implementation of the platform and one , two and three years later .\nin the digital platform the guideline for people with schizophrenia will be implemented and also information for clients and their home caregivers . when the platform is ready clients will be able to communicate digital with their caregivers in the mental health institute and with their home caregivers and gps .\nthe effect evaluation starts in september 2009 , the process evaluation has started in may 2009 .\nwe will have the first results in june 2009 ; they will be used to adjust the implementation and the development of the dm platform . in the meantime\nwe can report about the building of the dm platform and what the expectations from the future users are .\n what are the factors that influence the process of implementation of a digital tool that provides help and care on a distance ?\n in what way does the digital tool ( care from a distance ) stimulate people who need chronically care to be more self - supporting ? in what way does the digital tool support professionals to be able to stimulate people with schizophrenia to be more self - supporting ?", "answer": "purposeimproving quality of life and quality and management of care of clients with a schizophrenic disorder by the use of a comprehensive internet based disease management ( dm ) platform . presenting factors influencing the implementation of an internet based dm platform for clients with schizophrenia.contextthe project started in december 2008 . \n two mental health care institutions in the south of the netherlands participate in the implementation of the digital instrument ( the dm platform).the implementation of the dm platform will be followed by a process and an effect evaluation.data sourcemeasurement instruments : in the effect evaluation , quality of life , number of symptoms of schizophrenia , quality of care , social functioning , self management , and insight in schizophrenia and its treatment will be measured . \n process evaluation : semi - structured interviews will be held with different ( formal primary and secondary , and informal ) caregivers , managers and clients of each institute . these interviews will be conducted before the implementation of the platform and one , two and three years later.case descriptionin the digital platform the guideline for people with schizophrenia will be implemented and also information for clients and their home caregivers . when the platform is ready clients will be able to communicate digital with their caregivers in the mental health institute and with their home caregivers and gps . \n they also get information and feed - back about their illness and psycho education.(preliminary ) conclusionsthe effect evaluation starts in september 2009 , the process evaluation has started in may 2009 \n . we will have the first results in june 2009 ; they will be used to adjust the implementation and the development of the dm platform . \n in the meantime we can report about the building of the dm platform and what the expectations from the future users are.discussion what are the factors that influence the process of implementation of a digital tool that provides help and care on a distance? in what way does the digital tool ( care from a distance ) stimulate people who need chronically care to be more self - supporting? in what way does the digital tool support professionals to be able to stimulate people with schizophrenia to be more self - supporting ?", "id": 294} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 21-year - old man ( height = 180 cm , weight = 95 kg , body mass index = 29.3 kg / m ) presented to the outpatient department with a long history of frequent and severe snoring . on physical exam ,\nafter a diagnosis of obstructive sleep apnea was made , a bilateral tonsillectomy and uvulopalatopharyngoplasty was planned for treatment .\nprior to surgery , the patient had normal laboratory results with hemoglobin ( hb ) of 15.8 g / dl and no systemic or hematological diseases or history of bleeding disorders . on the day of the surgery , the patient received no premedication due to the history of sleep apnea .\nintraoperative monitors included electrocardiogram , non - invasive blood pressure ( bp ) , pulse oximetry ( spo2 ) , and end - tidal co2 .\npre - anesthetic vital signs were bp 120/82 mmhg , hr 68 bpm , and spo2 96% .\ngeneral anesthesia was induced with remifentanil 0.5 g / kg / min and propofol 180 mg iv at 10:10 am . at loss of eyelash reflex ,\ncisatracurium 16 mg was administered , and the trachea was intubated after a short period of facemask ventilation .\nanesthesia was maintained with sevoflurane 2 vol% in 50% oxygen - enriched air and remifentanil 0.2 g / kg / min .\nthe neuromuscular block was antagonized with glycopyrrolate 0.6 mg and pyridostigmine 15 mg iv without neuromuscular monitoring upon the completion of the surgical procedure at 11:25 am .\npostoperatively , a physical examination confirmed the presence of acute bleeding in the left inferior pole of the tonsillectomy site in the post anesthetic care unit .\nthe surgeon requested an emergent re - operation under general anesthesia for the control of bleeding .\na rsi for a second round of general anesthesia was performed with propofol 120 mg , midazolam 5 mg , and rocuronium 100 mg at 11:55 am .\nthe surgeon confirmed active bleeding due to an aberrant arterial blood supply in the left inferior pole of the tonsillectomy site .\nafter the completion of the surgical procedure , no twitch was shown after train - of - four ( tof ) stimulation ( tof = 0 ) with neuro - stim ( model ns-3cc , houston , tx , usa ) at 12:40 pm . the neuromuscular block was then antagonized with sugammadex 200 mg iv and the rocuronium - induced nmb was completely reversed within 2 min .\nthe patient was transferred to the recovery room , and there were no specific findings on physical exam .\na post - operative laboratory assessment showed hb of 14.6 g / dl ( table 1 ) .\nafter 6 h and 20 min , the surgeon again requested emergent anesthesia and re - operation for control of bleeding .\nthe surgeon attempted to control bleeding at the ambulatory otolaryngology clinic but was unable to do so .\nwhen the patient arrived at the operating room ( or ) , vital signs were within normal limits and hb was found to be 13.2 g / dl .\na third round of general anesthesia was induced with propofol 120 mg and rocuronium 40 mg by the on - call resident at 19:00 pm .\nthe neuromuscular block was antagonized with sugammadex 200 mg iv and a tof = 0 at 20:00 pm .\nthe patient was again extubated successfully and transferred to the recovery room with no specific findings ( table 1 ) . after 2 h and 35 min ,\nwhen the patient arrived at the or , vital signs were stable and hb was 11.6 g / dl .\na fourth induction of general anesthesia was performed with propofol 120 mg and rocuronium 40 mg by the same resident at 22:35 pm . during tof stimulation\n, 1 twitch was seen , and an additional dose of rocuronium 10 mg was given due to bucking 20 min after the induction of anesthesia . at the end of the procedure ,\nthe neuromuscular block was antagonized with glycopyrrolate 0.4 mg and pyridostigmine 10 mg iv with a tof = 1 at the end of the surgical procedure at 0:20 am .\nextubation was carried out after confirming the recovery of consciousness , regular respiration , and the absence of fade on tof monitoring .\nafter extubation , the patient vomited a large amount of blood on the operating table ( approximated to be more than 200 ml ) .\nhowever , the patient was alert and aware of his surroundings and had regular respirations ( table 1 ) .\nafter 20 min , the surgeon requested a re - induction of general anesthesia for additional bleeding control .\nan rsi for a fifth round of general anesthesia was performed with propofol 120 mg and rocuronium 100 mg at 0:40 am .\nthe neuromuscular block was antagonized with glycopyrrolate 0.4 mg and pyridostigmine 10 mg iv with a tof = 1 after the surgical procedure was completed at 1:30 am .\napproximately 15 min passed after the nmb was antagonized as above , but no evidence of recovery from the rocuronium - induced nmb was seen .\ntherefore , we injected a bolus of iv sugammadex 200 mg to reverse the residual nmb .\nonce again , the nmb was completely reversed within 2 min , and tracheal extubation was performed in the or uneventfully ( table 1 ) .\na decision by surgeon was made to perform angiography of the left external carotid artery with subsequent embolization of the bleeding vessel .\nembolization of the left ascending pharyngeal artery was performed with polyvinyl alcohol particle ( 350 m ) and tornado embolization microcoil ( cook , bloomington , usa ) ( 3/2 mm ) ( fig .\nthe patient 's postoperative course was uneventful , and hb was found to be 10.5 g / dl .\npth occurs in approximately 1 in 20 adults ( 5.1% ) , and more than half of patients who bleed are likely to require a procedure of some type to control their hemorrhage .\naberrant arterial blood supply to the tonsillar region derived from the internal carotid artery or the carotid bulb may be present .\nto control bleeding , electrocauterization , packing of the pharynx , or angiographic embolization of the feeding artery may become necessary .\nthe endovascular embolization due to refractory bleeding after tonsillectomy proved to be a valuable treatment method as an effective alternative to surgical intervention .\nit is a safe and permanent treatment option in this potentially life - threatening complication . in a case such as this ,\nthe aberrant arterial blood supply in the left inferior pole of tonsillectomy site caused continuous bleeding .\nthe anesthesiologist has experienced difficulties , because an experienced surgeon has embarrassed due to repetitive bleeding . in the first induction of anesthesia\n, no problems were encountered with conventional anesthesia , although neuromuscular monitoring was not performed .\nthe most common anesthetic used for rsi during the management of children with pth is succinylcholine . since the introduction of sugammadex , rsi with rocuronium followed by reversal with sugammadex allowed for earlier establishment of spontaneous ventilation than with succinylcholine , which has many adverse side events . during the second round of anesthesia , rocuronium 100 mg ( 1 mg / kg )\nwas injected for rsi , followed by reversal with sugammadex 200 mg ( 2 mg / kg ) at deep nmb ( tof = 0 ) . during the operation ,\nnmb monitoring was difficult due to problems attaching leads to the arms during the operation .\ntof stimulation was applied at the ulnar nerve using conventional instrumental monitoring rather than quantitative monitoring due to convenience .\ndeep nmb was maintained for bleeding control in an attempt to not disturb the procedure . during nmb reversal\n, we found an absence of fade on tof monitoring just 2 min after sugammadex was administered .\nre - administration of 0.6 mg / kg rocuronium could then be given after sugammadex at the recommended waiting time of 6 h . during the third anesthesia induction ,\nan on - call resident used rocuronium 40 mg for muscle relaxation during intubation followed by reversal with sugammadex 200 mg at deep nmb ( tof = 0 ) .\nan absence of fade on tof monitoring was shown 2 min after sugammadex was given . for the fourth round of anesthesia , the same resident used rocuronium 40 mg for intubation 2 h and 35 min after the previous nmb reversal with sugammadex .\nhowever , we believe this decision was made without considering the recent sugammadex use . when rocuronium is used within a short time interval ( less than 6 h ) after sugammadex administration , the onset time of rocuronium may be prolonged and may also have an unpredictable duration of action .\nwe suspect that the additional dose of rocuronium 10 mg due to bucking may be related to the short time interval between sugammadex and rocuronium administration . in situations such as these ,\nthe benzylisoquinoline class of medications are recommended instead of re - administering rocuronium within 6 h after sugammadex .\nwhen considering this case , cisatracurium for muscle relaxation and intubation may have been a better choice for the fourth round anesthesia . however , one drawback of cisatracurium is the slower onset time than rocuronium .\nreversal of the rocuronium - induced nmb with pyridostigmine at a moderate nmb ( tof = 1 ) was uneventful .\nafter extubation , the patient vomited more than 200 ml of blood on the operating table ; however , he was alert and showed regular respirations .\npostoperative nausea and vomiting ( ponv ) after an operation for pth is common due to blood swallowed during the procedure .\ntherefore , patient awareness and complete reflexes are important , but aspiration must be avoided and monitored closely during the recovery period . however , ponv increases the risk of primary hemorrhage and unexpected postoperative hospital admissions . in this case\nthe patient did not aspirate , but did have an increased risk of pth due to ponv .\nfor the fifth round of anesthesia , rocuronium 100 mg ( 1 mg / kg ) was injected for rsi after a time interval from sugammadex administration of 4 h and 40 min .\nit has been reported that re - administration of 1.2 mg / kg rocuronium could have been given after sugammadex 2 mg / kg without a waiting time .\nhowever , neuromuscular monitoring did not show the expected recovery , and the patient had residual paralysis after 15 min .\nit has been shown previously that the reversal of nmb with anticholinesterase drugs may not be complete after a large dose of a neuromuscular blocking agent .\nsugammadex resolved the residual nmb within 2 min , even after reversal with anticholinesterase agents , and is a safe alternative to reversal of nmb induced by steroidal non - depolarizing agents . in this case , deep rocuronium - induced nmb can be reversed successfully with sugammadex at doses of 2 mg / kg and in as little as 2 min .\nre - administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of the nmb agent .\nsugammadex made it possible to perform a rapid , complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase .", "answer": "post - tonsillectomy hemorrhage ( pth ) is the most frequent complication of tonsillectomy , and occasionally results in a lethal outcome . \n a 21-year - old man ( height 180 cm , weight 95 kg ) was scheduled for a bilateral tonsillectomy and uvulopalatopharyngoplasty for treatment of obstructive sleep apnea . \n he required 5 rounds of general anesthesia due to recurrent pth . \n the anesthesiologist used sugammadex a total of 3 times to achieve the successful reversal of the deep neuromuscular blockade ( nmb ) induced by rocuronium . \n after sugammadex 2 mg / kg was administered , the nmb was reversed in 2 minutes each time . \n re - administration of rocuronium within a short time interval after sugammadex may result in unpredictable effects of neuromuscular blocking agents . \n sugammadex made it possible to perform a rapid , complete reverse when the residual block was maintained by an incomplete reversal of anticholinesterase .", "id": 295} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute cholecystitis is an inflammation of the gallbladder due to obstruction of the neck or cystic duct , primarily caused by gallstones .\nacute cholecystitis is characterized as a combination of local and systemic inflammation , and its treatment is dependent on the severity , although it is often treated conservatively with antibiotics .\nwhen acute cholecystitis becomes severe , it is treated surgically , while for some patients , percutaneous transhepatic gallbladder drainage ( ptgbd ) is an alternative to surgery .\nan accurate assessment of the severity is critical for the appropriate management of acute cholecystitis .\nabdominal ultrasonography ( us ) is useful for the diagnosis of diseases of the abdominal cavity . with abdominal us ,\nhowever , this condition can be treated more appropriately if the severity is evaluated , using diagnostic imaging prior to the occurrence of organ failure or worsening of blood test variables . with regard to diagnostic imaging\n, wall thickening is representative of edema and correlates with the severity of acute cholecystitis , while inflammation is indicated by both edema and increased blood flow . if blood flow is assessed using abdominal us , it is possible to more accurately evaluate the severity of acute cholecystitis .\nsuperb microvascular imaging ( smi ) is based on color doppler imaging of abdominal us and enables the visualization of very slow blood flow without requiring contrast medium .\nit is composed of color - coded ( csmi ) and monochrome smi ( msmi ) , where csmi visualizes pulsatory signals such as color doppler images and msmi enhances the blood flow signal by suppressing background signaling .\n, we present the changes observed using csmi and msmi over the course of an acute cholecystitis in 1 patient .\nan 84-year - old man was admitted to the national hospital organization shimoshizu hospital with right upper abdominal pain that persisted for 3 days .\nwhite blood cell count ( wbc ) and c - reactive protein ( crp ) levels were 11.4 10/l and 15.3 mg / dl , respectively .\ntotal bilirubin , alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase , and -glutamyl transpeptidase levels were 1.5 mg / dl , 206 iu / l , 20 iu / l , 10 iu / l , and 10\nthe possibility of obstructive jaundice was low . to clarify the cause of inflammation , computed tomography ( ct ) scans ( somatom emotion 16 ; siemens , munich , germany ) were performed , which showed slight thickening of the gallbladder wall ( fig .\n1a ) . to confirm the results of the ct scans , the patient was subjected to abdominal us ( applio 400 ; toshiba medical , ohtawara , japan ) with a curved array transducer ( pvt-375bt ) at 3.75 mhz ( toshiba medical ) .\nthe severity was classified as mild as the patient showed no signs of organ failure .\ndiagnostic imaging found no evidence of marked local inflammation such as pericholecystic or hepatic abscess .\nthe patient was treated conservatively with antibiotics ( cefazolin sodium 3 g / day ) intravenously from the date of admission .\nafter 2 days of treatment , right upper abdominal pain still persisted , and his body temperature rose to 38.7c .\nwbc and crp levels rose to 15.6 10/l and 19.6 mg / dl , respectively .\nthese data indicated that the acute cholecystitis had worsened . to evaluate the acute cholecystitis morphologically ,\nabdominal us showed that the wall thickness of the gallbladder had increased and a sonolucent area was visible ( fig .\ncomplications , such as liver abscess or peritonitis , were considered possible . to avoid complications and promote recovery ,\nseven days after ptgbd , wbc and crp levels were 6.8 10/l and 1.2 mg / dl , respectively , also confirming recovery .\n, csmi showed a pulsatory signal on the wall of the gallbladder with the curved array transducer ( 2.0 cm / s ; pvt-375bt ) at 3.75 mhz ( fig .\n2a ) , whereas no such signal was observed on the wall with msmi ( 2.2 cm / s ) ( fig .\nwhen his acute cholecystitis had worsened , this signal became more evident with csmi ( fig .\nafter ptgbd , the gallbladder shrank due to drainage of the gall and the pulsatory signal was no longer visible with either csmi ( fig .\nabdominal us is recommended as a first - line diagnostic imaging tool for the diagnosis of acute cholecystitis ; however , false negatives are a known issue of this technique . in our case , a pulsatory signal was observed on the wall of the gallbladder on the day of admission , which suggested positive csmi , even when wall thickening was minimal .\nsmi is expected to reduce the incidence of false negatives when diagnosing this condition . in the present case , the strength of the pulsatory signals correlated with the severity of the gallbladder inflammation , as illustrated using both csmi and msmi .\nthe results suggest that the signal intensity of csmi and msmi is correlated with the severity of inflammation .\nour case shows that both csmi and msmi are useful for the diagnosis and evaluation of the severity of acute cholecystitis .\ncontrast - enhanced abdominal us shows a strong enhancement that successfully differentiates acute cholecystitis from a healthy gallbladder and chronic cholecystitis .\nhowever , unlike contrast - enhanced abdominal us , smi does not require contrast medium and is therefore suitable for the management of acute cholecystitis .\na primary limitation of the present study is that it is based on just 1 case of acute cholecystitis . in order to confirm the usefulness of smi for the evaluation of the severity of acute cholecystitis\n, more patients should be enrolled in larger studies and smi findings for acute and chronic cholecystitis compared .\nfurthermore , signal intensity should be stratified against the severity of acute cholecystitis . in conclusion ,\na strong pulsatory signal correlated with the severity of acute cholecystitis with both csmi and msmi and may be suitable for the evaluation of the severity of this condition .\nthis report was approved by the ethical committee of the national hospital organization of shimoshizu hospital .\nthe study was considered an element of daily clinical practice as opposed to a clinical trial .\nwritten informed consent was obtained for the performance of contrast - enhanced ct and ptgbd .\nthe patient 's records were anonymously and retrospectively analyzed , and written informed consent was obtained for their use in this report .", "answer": "evaluation of the severity of acute cholecystitis is critical for the management of this condition . \n superb microvascular imaging ( smi ) enables the assessment of slow blood flow of small vessels without any contrast medium . \n an 84-year - old man visited our hospital with right upper abdominal pain . computed tomography and abdominal ultrasonography showed a slight thickening of the gallbladder . \n white blood cell count and c - reactive protein levels were elevated . \n he was diagnosed with acute cholecystitis and treated conservatively with antibiotics . \n two days later , his condition worsened and percutaneous transhepatic gallbladder drainage ( ptgbd ) was performed . \n the patient recovered and was discharged , and his drainage was withdrawn 7 days later . on admission , \n color - coded smi ( csmi ) showed pulsatory signals on the slightly thickened gallbladder wall . on the day of ptgbd \n , the intensity of the signal on csmi had increased . \n once the patient was cured , no further signal was observed on the gallbladder wall with either csmi or msmi . in conclusion , the strong pulsatory signal correlated with the severity of acute cholecystitis observed with csmi and msmi . illustrating the signal intensity is useful for the evaluation of the severity of acute cholecystitis .", "id": 296} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngenomic dna hypomethylation has been observed in the peripheral blood mononuclear cells of leukemia patients and in tumor cells of patients with b - cell lymphoproliferative diseases ( 1 ) .\ndna methylation may affect karyotypic stability , may influence euchromatin - heterochromatin interactions , and has been correlated with disease progression ( 2 ) . on the other hand ,\nfor example , some patients with lymphomas do not express tumor suppressor genes because the promoters of these genes are methylated .\n, bone marrow produces a large number of abnormal white blood cells , which overwhelm the other types of blood cells , including red blood cells and platelets , thus impairing the production of normal white blood cells . in clinical classification , leukemia can be classified as acute myeloid leukemia ( aml ) and chronic myeloid leukemia ( cml ) .\ncml is a clonal disease of stem cell origin that is characterized by the presence of the philadelphia chromosome ( ph+ ) , which has been named t(9,22)(q34:q11 ) .\nits fusion gene product , bcr - abl , is a constitutively active tyrosine kinase .\nnevertheless , the differential factors through which they produce a different type of leukemia are not yet completely understood . in hematopoietic malignancies ,\nhypermethylation of several genes including e - cadherin , dap kinase , estrogen receptor ( er ) alpha , and p15 are associated with gene inactivation ( 7 - 10 ) .\ngenes , such as dab2ip , dlc-1 , h - cadherin , id4 , integrin 4 , runx3 , sfrp1 , and shp1 , has been identified as being implicated in aberrant dna methylation during development of human malignancy ( 11 - 18 ) . in order to gain insight into the differential epigenetic alterations in leukemia , we investigated the methylation statuses at selected locus of these genes in aml and cml patients using a methylation - specific polymerase chain reaction ( msp ) .\ndiagnostic bone marrow samples were obtained from 23 patients with aml and 21 patients with cml .\nthe samples were gathered by the division of hematology / oncology ( department of internal medicine , korea university medical center , seoul , republic of korea ) and analyzed by pathologist . institutional review board approval and informed consent were obtained ( kumc - irb-2006011-p-1 , kumcirb-2006012-p-2 ) . of the aml patients , 17 males and 6 females were included , with ages ranging from 26 to 78 yr , at a median age of 45.61 ( sd , 15.56 ) yr . of the cml patients ,\n11 males and 10 females were included , with ages ranging from 18 to 75 yr ( meansd , 49.9116.53 ) . as controls ,\n22 normal peripheral bloods were obtained from healthy volunteers ( 11 males and 10 females ) ranging from 20 to 78 yr of age ( meansd , 45.3620.64 ) .\nchemical modification was performed as described previously , with minor modifications ( 19 ) . in brief\n, 1 g of genomic dna was denatured by incubation with 0.2 m naoh for 10 min at 37 , followed by the addition of 550 l of 3 m sodium bisulfite ( ph 5.0 ) ( sigma , st .\nlouis , mo , u.s.a . ) and 10 mm hydroquinone ( sigma ) , which was brought to a final volume of 600 l .\nthe mixtures were incubated at 55 for 16 hr , and the modified dna was then desalted with the wizard clean - up system ( promega corp . ,\nwe performed polymerase chain reaction ( pcr ) using specific pcr primers capable of distinguishing between methylated and unmethylated dna sequences .\nthe primers for the unmethylated and methylated dna sequences , pcr product size , and annealing temperature are shown in table 1 .\nthe msp primer sets were selected at the 5'-cpg island regions of genes using the methprimer software ( www.urogene.org ) .\nthe pcr conditions were as follows : initial denaturation and hot start at 95 for 5 min , and cycles consisting of 30 sec at 95 , 30 sec at the annealing temperature , and 30 sec at 72. in addition , sck , a human cholangiocarcinoma cell line , was used as positive control for integrin 4 gene ( 20 ) .\nmsp results were analyzed as a dichotomous variable based on the presence or absence of gene methylation .\nthe msp results of tumor and normal samples were compared and analyzed with the pearson chi - square test ( version 12 ; spss inc . ,\ndiagnostic bone marrow samples were obtained from 23 patients with aml and 21 patients with cml .\nthe samples were gathered by the division of hematology / oncology ( department of internal medicine , korea university medical center , seoul , republic of korea ) and analyzed by pathologist . institutional review board approval and informed consent were obtained ( kumc - irb-2006011-p-1 , kumcirb-2006012-p-2 ) . of the aml patients , 17 males and 6 females were included , with ages ranging from 26 to 78 yr , at a median age of 45.61 ( sd , 15.56 ) yr . of the cml patients ,\n11 males and 10 females were included , with ages ranging from 18 to 75 yr ( meansd , 49.9116.53 ) . as controls ,\n22 normal peripheral bloods were obtained from healthy volunteers ( 11 males and 10 females ) ranging from 20 to 78 yr of age ( meansd , 45.3620.64 ) .\nchemical modification was performed as described previously , with minor modifications ( 19 ) . in brief\n, 1 g of genomic dna was denatured by incubation with 0.2 m naoh for 10 min at 37 , followed by the addition of 550 l of 3 m sodium bisulfite ( ph 5.0 ) ( sigma , st .\nlouis , mo , u.s.a . ) and 10 mm hydroquinone ( sigma ) , which was brought to a final volume of 600 l .\nthe mixtures were incubated at 55 for 16 hr , and the modified dna was then desalted with the wizard clean - up system ( promega corp . ,\nwe performed polymerase chain reaction ( pcr ) using specific pcr primers capable of distinguishing between methylated and unmethylated dna sequences .\nthe primers for the unmethylated and methylated dna sequences , pcr product size , and annealing temperature are shown in table 1 .\nthe msp primer sets were selected at the 5'-cpg island regions of genes using the methprimer software ( www.urogene.org ) .\nthe pcr conditions were as follows : initial denaturation and hot start at 95 for 5 min , and cycles consisting of 30 sec at 95 , 30 sec at the annealing temperature , and 30 sec at 72. in addition , sck , a human cholangiocarcinoma cell line , was used as positive control for integrin 4 gene ( 20 ) .\nmsp results were analyzed as a dichotomous variable based on the presence or absence of gene methylation .\nthe msp results of tumor and normal samples were compared and analyzed with the pearson chi - square test ( version 12 ; spss inc . ,\nthe multiple genes were found to be methylated in bone marrow from patients with aml or cml . specifically , the frequencies of promoter hypermethylation at selected locus in the 23 aml samples were : 78.3% ( 18/23 ) for shp1 , 65.2% ( 15/23 ) for id4 and sfrp1 , 26.1% ( 6/23 ) for h - cadherin , 8.7% ( 2/23 ) for dlc-1 , and 4.3% ( 1/23 ) for dab2ip and runx3 .\nthe frequencies of dna hypermethylation at selected locus in the 21 cml samples were : 28.6% ( 6/21 ) for shp1 , 19.0% ( 4/21 ) for h - cadherin , 14.3% ( 3/21 ) for id4 , 9.5% for ( 2/21 ) for sfrp1 , and 0% ( 0/21 ) for dab2ip , dlc-1 , integrin 4 , and runx3 ( fig .\nhowever , promoter hypermethylation of the 22 normal peripheral bloods was observed less frequently ( table 2 ) . there was a statistically significant difference between normal peripheral bloods and aml with respect to the frequencies of methylation of id4 , sfrp1 , and shp1 ( pearson chi - square test ; p<0.0001 , p<0.0001 , and p<0.0001 , respectively ) and between normal peripheral bloods and cml with respect to the frequencies of shp1 methylation ( pearson chi - square test ; p=0.007 )\n. furthermore , there was a statistically significant difference between the dna methylation frequencies of aml patients and cml patients .\nthe frequencies of dna methylation of id4 , sfrp1 , and shp1 were higher in aml compared to those in cml ( p=0.001 , p<0.0001 , and p=0.001 , respectively ) ( table 2 ) .\nin contrast , no statistical differences between aml and cml were detected in other genes such as dlc-1 , dab2ip , h - cadherin , integrin 4 , and runx3 .\npromoter methylation results at selected locus of eight genes with msp method were shown in fig .\nthe results of the present study demonstrate the substantially increased frequency of promoter hypermethylation in id4 , sfrp1 , and shp1 genes in aml compared to cml .\nleukemia , a heterogeneous group of hematopoietic malignancies that occur worldwide , includes acute and chronic myeloid leukemia . despite many important advances in understanding the different biological and cytogenetic aspects of acute and chronic leukemia ,\nit is understood that some kinds of leukemia present specific cytogenetic alterations ( 21 ) .\ndifferent types of leukemia usually have specific epigenetic modifications that cause the activation of oncogenes and , in particular , the formation of abnormal fusion genes such as aml1-eto ( 22 , 23 ) , a fusion protein resulting from t(8,21 ) translocation that commonly occurs in aml .\nanother typical example is the fact that bcr - abl is a constitutively active , cytoplasmic tyrosine kinase that is generated by t(9;22 ) translocation in more than 95% of cml ( 24 ) .\nthe central role of epigenetic modification of these genes in leukemia development promoted them as reasonable targets for understanding the differential mechanism between acute and chronic leukemia . in the present study , id4 , sfrp1 , and ship1\nthese results suggest that the epigenetic modification of these genes may play specific roles in the development of aml rather than cml and , thus , promoted them as ideal targets for drug development to treat aml . in the future , it is clearly imperative to understand the patho - physiological differential mechanisms of these genes in aml , and to finally explore novel therapeutic strategies . in present study ,\nmethylation frequencies of shp1 gene were the high detected in cml as well as aml .\nshp1 is a member of the shp family of proteins , cytoplasmic protein tyrosine phosphatase ( ptp ) , and has been known as a candidate tumor suppressor gene in lymphoma , leukemia and other cancers ( 25 ) .\nalso , the hypermethylation of shp1 gene was frequently detected in several human cancers and the reduced expression of the shp1 gene in various types of leukemias and lymphomas mainly occurred by promoter methylation ( 26 - 28 ) . therefore , these results indicate that aberrant dna methylation of shp1 gene may be related to the tumorigenicity of myeloid leukemia .\nthe methylation frequencies of the dab2ip , dlc-1 , and runx3 genes were detected at different levels in acute and chronic leukemia patients ; however , the difference was negligible . in some genes like integrin 4 gene ,\nhowever , hypermethylation of these genes was frequent event in esophageal squamous cell carcinomas , lung cancers , and gastric cancers ( 11 , 12 , 15 , 16 ) .\nthus , dna methylation of these genes may be not related to tumorigenicity of aml / cml in contrast with other cancers . in summary , we have identified that aberrant dna methylation of shp1 is a frequent event in aml and cml . also , the frequencies of dna methylation of several methylation - controlled genes , including id4 , sfrp1 , and shp1 , were higher in aml patients compared to those in cml patients .\nalthough these results should be confirmed , more comprehensive studies are necessary involving various known risk factors such as smoking and occupational carcinogens , and genetic susceptibilities .\nour results suggest that aberrant dna methylation of shp1 may be related to the tumorigenicity of aml and cml and hypermethylation of id4 , sfrp1 , and shp1 genes may contribute to the pathogenesis mechanism of aml specifically .", "answer": "to gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia , we identified the methylation status on one part of 5'cpg rich region of 8 genes , dab2ip , dlc-1 , h - cadherin , id4 , integrin 4 , runx3 , sfrp1 , and shp1 in bone marrows from acute myeloid leukemia ( aml ) and chronic myeloid leukemia ( cml ) patients . also , we compared the methylation status of genes in aml and cml using methylation - specific pcr ( msp ) . \n the frequencies of dna methylation of id4 , sfrp1 , and shp1 were higher in aml patients compared to those in cml patients . in contrast , no statistical difference between aml and cml was detected for other genes such as dlc-1 , dab2ip , h - cadherin , integrin 4 , and runx3 . \n taken together , these results suggest that these methylation - controlled genes may have different roles in aml and cml , and thus , may act as a biological marker of aml .", "id": 297} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhardware removal is indicated for infection , nonunion , failure of fixation , pain , soft tissue irritation , and anticipated strenuous activity after fracture healing [ 14 ] . during removal cases\nsubsequent removal of broken hardware increases surgical time , and retained metalwork potentially complicates future surgeries ( figure 1 ) . \nalthough there have been several articles that have discussed titanium implant failure , most have discussed this issue within the context of hardware failure during fracture healing , and not particularly during removal of hardware [ 69 ] . to our knowledge\n, none have been specific to the elbow , which merits its own discussion due to its unique anatomy .\nthe distal humerus of the elbow is unique in that is has a high ratio of cortical to cancellous bone .\ntherefore , in this study we set out to investigate incidence of bone screw failure during hardware removal procedures and we were interested in comparing titanium and stainless steel bone screws because these are the most common types of metallic fracture implants in circulation .\nin addition , we set out to determine whether the duration of implantation and the anatomic location of the bone screws about the elbow were associated with bone screw failure during removal procedures\n. a better understanding of metallic hardware failure during removal procedures may help surgeons in the preoperative planning stages of these cases , in terms of surgical tool selection and staff availability .\nafter institutional review board ( irb ) approval , all cases performed by orthopaedic trauma or upper extremity surgeons between 1/1/2000 and 10/1/2009 at our level 1 trauma center were reviewed .\ninclusion criteria were ( 1 ) deep implant removal cases , ( 2 ) hardware removed from the distal humerus or the proximal ulna , and ( 3 ) isolated elbow injuries .\nthe exclusion criteria were ( 1 ) cases that did not have relevant or inaccessible elbow x - rays , ( 2 ) single screw fragment extraction cases ( because in these cases the hardware had previously broke and was small in size , which we believe was not representative of the other screws being removed ) , ( 3 ) patients younger than 17 years , and ( 4 ) cases that were originally performed at an outside institution ( unavailable medical records ) . the factors considered were ( 1 ) whether or not the bone screws broke during removal and the type of implant metal used ( titanium alloy , ti6al4v or stainless steel ) , ( 2 ) the length of time between initial implantation and removal , where cases were divided into two groups based on a conservative estimate of the time period required for osseointegration of titanium implants [ 10 , 11 ] : one group was for cases where the duration of time between implantation and removal was less than 12 months and the second group was for cases where the duration between implantation and removal was 12 months or more ; and ( 3 ) anatomic location about the elbow ( distal humerus or proximal ulna ) .\nthe data was extracted from the medical record . due to the small sample size , fisher 's exact test was used to determine statistical differences between two sets of categorical data .\nan independent t - test was used to compare the means of two independent groups .\ndifferences that had less than 0.05 probability of occurring from chance were considered statistically significant .\nwe identified a total of 47 cases , of which 21 met the inclusion criteria .\nwe carried out an independent t - test to determine if there were any differences between the ages of patients that had broken screws and those that did not , and no statistical significance was found , p = 0.740 .\nout of 21 cases , screws broke during removal in 5 cases ( 23.8% ) . in 16 out of 21 cases ,\nthe reasons for hardware removal were infection in 7/21 cases , symptomatic , prominent hardware in 7/21 cases , nonunion in 6/21 cases , and contracture in 1/21 cases . \n14 involved titanium alloy and 7 involved stainless steel implants . within the titanium hardware group , in 10 cases removal was uneventful , and in 4 cases , fracture of at least one screw occurred . in comparison , out of the 7 stainless steel hardware removal cases , there was one case that resulted in one or more broken screws .\noverall , compared to stainless steel , failure of titanium alloy screws during removal was not found to be statistically significant ( p = 0.61 ) . in order to determine whether there were any association between the duration of implantation and hardware failure during removal\n, cases were divided into two groups : group ( 1 ) duration of hardware implantation was 12 months or less ( mean 7.7 , range two to 12 months ) , and group ( 2 ) : duration of implantation was more than 12 months ( mean 41.6 , range 16 to 74 months ) .\ntwelve cases had hardware removed within 12 months of implantation and nine cases had hardware removed after 12 months of initial implantation .\nbone screws that were removed after 12 months of surgery were more likely to break during removal ( p = 0.046 ) .\nwhen titanium screws were analyzed separately , those removed within 12 months of surgery were more likely to be removed intact as compared to those removed more than 12 months after implantation ( p = 0.003 ) . the small number of stainless steel cases ( seven ) did not warrant statistical calculations .\nwith respect to anatomic location , there were 12 distal humerus and 15 proximal ulna cases ( table 1 ) .\nsix cases involved the distal humerus only , nine cases involved the proximal ulna only , and six cases had simultaneous proximal ulna and distal humerus involvement . in one case where titanium screws broke and in one case where stainless steel screws broke , it was unclear where the location was and these cases were discarded from the analysis . in general , bone screw failure was equally likely to occur when removed from the distal humerus and the proximal ulna ( p = 0.28 ) .\nhardware failure during removal cases is a commonly seen problem in orthopaedics ( figure 1 ) .\ncurrently , there is no single hardware removal technique that is uniformly successful , and several different methods may be employed during the same case .\nsuch techniques include the use of screw extractors , trephines , extraction bolts , pliers , and various other devices .\nthe purpose of this article was to determine the incidence of bone screw failure during hardware removal procedures , and we were interested in comparing titanium and stainless steel bone screws .\nin addition , we set out to determine whether the duration of implantation and the anatomic location of the bone screws about the elbow had any association with bone screw failure during removal procedures .\nwe believe that prior knowledge of the type of metal implanted ( mainly titanium ) and the duration of implantation to be useful information that can help in the preoperative planning of hardware removal procedures .\nfirstly , this may allow surgeons to request hardware removal kits , thus saving precious operative time .\nsecond , it is our experience that hardware removal procedures are often considered not technically demanding and are often delegated to less experienced surgical staff such as junior residents who may be more likely to break the hardware .\ntherefore , we believe that experienced staff surgeons should be available during procedures where titanium is being removed . having broken hardware in the elbow may complicate future surgeries in the same region of the limb . with regards to orthopaedic implants\n, it is known that both titanium alloy and commercially pure titanium hardware are more predisposed to in situ fracture relative to stainless steel [ 69 ] . as compared to stainless steel ,\ntitanium alloy is lighter , has a lower modulus of elasticity , and has superior corrosion resistance and biocompatibility , but inferior ductility and notch sensitivity .\nthe literature search performed for this review did not reveal any previous studies that compare hardware removal from the elbow in vivo for titanium and stainless steel fracture implants .\nin contrast to titanium implants remaining in situ for less than 12 months , we observed that the titanium implants remaining in situ for more than 12 months had a tendency to fail during extraction . in this series , it is likely that a combination of titanium alloy 's fatigue properties secondary to notch sensitivity and osseointegration were responsible for this observation .\nthe fatigue strength of titanium alloy is generally comparable to stainless steel 316l , but notch sensitivity in both commercially pure titanium and titanium alloy has been shown to significantly shorten the fatigue life of these implants in comparison to stainless steel [ 1214 ] . \nosseointegration has been observed to occur within 310 months in titanium alloy [ 10 , 11 ] .\nthe degree of bone ingrowth and on - growth , however , continues to increase for years after initial implantation ( figure 2 ) .\nalthough there have been studies showing evidence of stainless steel osseointegration , it is generally accepted that commercially pure titanium and titanium alloy are more biocompatible and more likely to osseointegrate than stainless steel . in our series , it is likely that as osseointegrataion became more complete , greater removal torques contributed to the failure of titanium alloy screws in this series . given these properties , we postulate that over longer periods and increased loading cycles , the development of micofractures and osseointegration contributed to screw breakage during implant removal .\nsecondly , the cases studied were not uniform ; there were a wide variety fractures and hardware systems involved .\nin addition , due to the small number of cases it was necessary to include multiple surgeons .\nin addition , not all x - rays were available for review ; therefore we were not able to account for the type of hardware , such as locking or non locking plate technology . in this study\n, there appears to be a time - related association for bone screw failure during removal cases , and for titanium alloy in particular .\nthis is likely due to the increased bone ingrowth and the adverse effect of notch sensitivity on titanium alloy 's fatigue properties .", "answer": "a retrospective review of 21 patients that underwent bone screw removal from the elbow was studied in relation to the type of metal , duration of implantation , and the location of the screws about the elbow . \n screw failure during extraction was the dependent variable . \n five of 21 patients experienced hardware failure during extraction . \n fourteen patients had titanium alloy implants . in four cases , \n titanium screws broke during extraction . \n compared to stainless steel , titanium screw failure during removal was not statistically significant ( p = 0.61 ) . \n screw removal 12 months after surgery was more likely to result in broken , retained screws in general ( p = 0.046 ) and specifically for titanium alloy ( p = 0.003 ) . \n bone screws removed from the distal humerus or proximal ulna had an equal chance of fracturing ( p = 0.28 ) . \n there appears to be a time - related association of titanium alloy bone screw failure during hardware removal cases from the elbow . \n this may be explained by titanium 's properties and osseointegration .", "id": 298} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npotential candidates include l - lactate , -hydroxybutyrate , d - lactate , salicylate , formate and oxalate in toxicological situations , pyroglutamate , semisynthetic penicillins , sulphate and hippurate in renal failure , and occasionally urate and amino acids with catabolic states and total parenteral nutrition .\nreports of increased tricyclic acid ( tca ) cycle anions in shock are now emerging . their presence\nis often inferred from the anion gap ( ag ) , calculated as [ na ] + [ k ] - ( [ cl ] + [ hco3 ] ) . when its reference range is exceeded , a search for unmeasured anions should commence , irrespective of the overall metabolic acid - base status , because a competing metabolic alkalosis can mask their presence .\nlikely culprits vary with the clinical scenario , but the search usually starts with l - lactate and -hydroxybutyrate . during this process , stoichiometry is tracked between ag ( measured ag normal ag ) and the summed concentrations of suspect anions ( always in meq / l , because we are dealing in electrical neutrality ) . if ag \nboth sensitivity and specificity are reduced by perturbations of albumin ( remembering that albumin negative charge forms the bulk of the normal ag ) , ph , [ ca ] , [ mg ] and [ phosphate ] .\nthe most promising alternative is the strong ion gap ( sig ) like the ag , the sig quantifies unmeasured anions minus unmeasured cations , but unlike its predecessor it is insulated from variations in [ albumin ] , [ phosphate ] , ph , [ l - lactate ] , [ ca ] and [ mg ] . in the previous issue of critical care , bruegger and\ncolleagues combine sig calculations with capillary electrophoresis , and report that anions associated with the tca cycle , specifically citrate and acetate , contribute to the metabolic acidosis of canine haemorrhagic shock .\ntheir data originate from an earlier experiment designed to investigate the benefits of a perflurocarbon - based oxygen carrier during resuscitation from a predefined oxygen debt .\ncapillary electrophoresis on specimens before shock , during shock and on resuscitation revealed maximal citrate elevations of 1.9 meq / l , whereas the peak acetate increase was 3.4\nalthough these findings fuel ongoing speculation concerning tca anions in shock , several potential confounders are worthy of comment . during preparation , the animals acquired major metabolic perturbations , with severe baseline hypoalbuminaemia ( 1.5 g / dl ) and impressive hyperchloraemia ( 130 mmol / l ) , but ( from the parent study ) only mild anaemia ( 11 g / dl ) .\nmost surprising in this context was a massive baseline plasma acetate ( 2.4 meq / l ) , which is 40 times the level reported from a previous study in dogs ( 0.06 mmol / l ) .\nthe postshock acetate peaked at 5.8 meq / l , over 30 times that in the previous report ( 0.19 mmol / l ) . to our knowledge such prodigious acetate levels are unprecedented outside the setting of exogenous administration .\nin the parent study , ringer 's solution 15 ml / kg per hour was documented as infused during all but the shock phase .\nif this was ringer 's acetate , and if the animals had received both saline ( as stated by bruegger and colleagues ) and ringer 's acetate , then this would explain much .\nof relevance is a report that exogenous acetate can elevate hepatic citrate . although the authors acknowledge that they re - infused blood containing citrate phosphate dextrose solution during the shock phase , thus introducing exogenous citrate\na final caveat is that charge and dissociation indices for human albumin used in this study differ from those for canine albumin , although the effect on sig calculations is probably small . until now ,\ntalk of unmeasured ions in critical illness has largely been speculative , based on discrepancies in ag or sig . nonetheless ,\nsince the late 1960s reports have emerged of accumulating tca cycle intermediates in shock and dysoxic states . the pattern reported by forni and colleagues in human metabolic acidosis differed substantially from the findings reported by bruegger and coworkers , with relatively small increases in isocitrate , -ketoglutarate , malate and d - lactate , and in some cases citrate and succinate . only on aggregate were these sufficient to inflate the ag .\nit is insufficient to invoke ' tissue stress ' to explain such increases in tca anions .\nelevations must be considered within the context of anaplerosis and cataplerosis , which combine to maintain adequate concentrations of tca intermediates .\nag = anion gap ; sig = strong ion gap ; tca = tricyclic acid .", "answer": "evidence is emerging that elevated concentrations of the intermediates of the citric acid cycle may contribute to unmeasured anions in critical illness . \n both the anion gap and the strong ion gap are used as scanning tools for recognition of these anions . \n the mechanisms underlying these elevations and their significance require further clarification .", "id": 299} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n the dissemination of hepatitis viruses among patients in hemodialysis ( hd ) centers is one of the most important causes of morbidity and mortality in end stage renal disease patients .\nwhile the introduction of vaccination programs and isolation of hd machines have limited the spread of hbv infection , its prevalence rates continue to be unacceptably high in most hd centers .\nprevalence of positive hepatitis b surface antigen ( hbsag ) ranged between 1.3% and 14.6% in asia - pacific countries and 13.3% in turkey [ 2 , 3 ] .\nhepatitis c virus ( hcv ) is also a major cause of liver disease in hd patients .\nprevalence of hcv in hd wards has been reported from 5% to 60% in different countries .\nhigh risk behaviors and blood transfusion are not the usual routes of hcv transmission in hd patients . environment of hd and failure to follow the safety measures for infection control may be the main cause of hcv dissemination in these centers .\naccordingly the kidney disease improving global outcome ( kdigo ) in 2008 and the center for disease control and prevention ( cdc ) in 2001 advised protocols for infection control in hd centers .\nprincipally , these recommendations are based on : ( a ) compliance with infection control protocols by healthcare professionals ( hcp ) , ( b ) performing viral serological tests periodically , and ( c ) continuing training courses for personnel [ 7 , 8 ] .\nthe main practical points to be considered are cleaning the rooms and patients ' area , disinfection of instruments , correct drug preparation , and regular hand hygiene [ 9 , 10 ] .\nappropriate staff training and regular monitoring for hepatitis viruses are also mandatory . in a study from saudi arabia , by utilization of these recommendations , no new case of hcv was found in a period of 2 years .\nviral hepatitis infections are still the challenging problem in hd centers in iran . in a review by alavian et al .\nserologic markers of hbv and hcv showed a declining trend from 3.8% and 14.4% to 2.6% and 4.5% , respectively , in recent years , but it varies in different parts of the country . in our recent report ,\nseroprevalence of hcv , hbv , and hcv - hbv coinfection was 7% , 7% , and 1.7% , respectively , in hd centers in kerman province .\nministry of health recommended universal anti - infective standard precautions to all hd centers but they are not supervised officially . in order to clarify the contributing risk factors for higher viral transmission in this part of country , this study was conducted to determine the compliance rate of hcp with safety recommendations of kdigo and cdc in southeast of iran .\nthis cross - sectional study was carried out in seven hd centers around the whole province of kerman , in 2011 .\nout of 208 hd patients , 91 cases were under healthcare services in kerman city , the center of the province and the remained 117 cases were distributed in other 6 cities .\nthe data were collected by using a check list based on the safety recommendations of cdc and kdigo protocols .\nthese recommendations are a major part of educational program both at the beginning of work and also during the annual retraining courses for hd personnel in iran .\nthe content of the check list comprised of three parts : ( a ) necessary care taken by the hcp ( 18 items ) , ( b ) periodic viral serological assessment ( 4 items ) , and ( c ) participation of hcp in retraining courses ( 4 items ) . the first part of the study was observed during working hours .\nafter the first part finished , the other two parts were assessed by interviewing with the hcp and reviewing the documents .\nwe defined the rate of observance of recommended protocols by hcp into four categories : ( a ) excellent : 90% , ( b ) good : 8089% , ( c ) adequate : 7079% , and ( d ) weak : less than 69% compared to standard ( 100% ) safety measures by cdc and kdigo protocols . \ndata were analyzed using spss version15 ( spss inc . , chicago , il , usa ) software .\ndialysis was performed in three running times : 138 ( 66.3% ) cases in the morning , 58 ( 27.9% ) cases in the evening , and 12 ( 5.8% ) cases at the night hours .\nhcp who worked in dialysis wards were 61 persons ( 36 females , 25 males ) with a mean age of 32.4 11.2 years old . \nthe first item of this section was the presence of a dedicated clean room in the hemodialysis wards .\nthe level of adherence of hcp was adequate to excellent in 10 items .\n weak adherence was observed in 7 items : not sharing of trolley to carry patients ' medications ( 29.8% ) , cleaning and disinfecting the shared instruments ( 46.2% ) , using single use materials for many patients ( 52.4% ) , carrying used materials in disposable and nonpermeable containers ( 51.9% ) , not returning of unused materials to the clean room ( 55.3% ) , adherence to adequate hand washing ( 58.7% ) and not drawing drug for injection to many patients from a single vial ( 67.3% ) .\na significant difference was observed for some of the items between working shifts ( table 1 ) .\nhbv monitoring including hbs ag detection , hbv vaccination , and regular measurement of hbs antibody ( ab ) titer had been performed in all of the patients .\nit covered 74.1% of men and 61.6% of women ( p = 0.063 ) . in case of persistent high alanine aminotransferase ( alt ) level and negative hcv ab , hcv pcr was measured in 2.4% .\ncompliance of hcp to report the new cases of positive hcv to the local cdc was 92% .\nmonitoring of viral markers had a significant difference in favor of other cities than kerman , the center of the province ( p < 0.001 ) ( table 2 ) .\nthe percentage of hcp who participated in the annual retraining courses were as hand hygiene practice , 76% ; use of protective instruments by hcp , 76% ; routes of dissemination of viruses , 52% ; methods of correct administration of medications , 47% ( figure 1 ) .\nthe aim of this study was to assess the rate of compliance of hcp with safety measures for control of hepatitis viruses in hd wards in southeast iran .\ncompliance of hcp with many items of kdigo and cdc recommendations was adequate to excellent .\nthe main noncompliant items were : sharing the medications trolleys , no disinfection of instruments , reuse of single use materials , return of unused materials to the clean room , and no adherence to hand hygiene .\nhd associated viral hepatitis are a challenging health problem around the world and especially in developing countries such as iran .\nprevalence of hbv in iranian general population declined to 2.6% due to public hbv vaccination and improved public health awareness in recent years .\nhcv prevalence is low in iranian general population and is estimated to be less than 1% . on the other hand , prevalence of hcv and hbv in hd wards in iran has been reported 524% and 7% , respectively [ 12 , 14 ] .\nit seems that poor compliance with infection control measures and inadequate disinfection of hd equipments play a major role in hepatitis virus dissemination . in several studies hd environment was the most important factor for hepatitis virus transmission .\nit is highly recommended that medicines should be prepared in clean areas away from dialysis apparatus and served in separate trays for different patients .\nmultidoses vials should not be used and the drugs should be carried in separate trolleys for each patient [ 17 , 18 ] . based on a survey on hd centers from usa in 2002 , hbv incidence was higher in centers with inappropriate drug preparation . in our study ,\npreparation and carrying medicines were served inadequately and they need to be revised by hd staffs .\nhd wards equipments including bed , chair and external surfaces of the dialysis apparatus and instruments like scissors , stethoscopes , and blood pressure cuffs should be cleaned and in cases should be disinfected for every patient .\nthese items were also among the other weak adherent points in our study .\nhand hygiene practices are mandatory for prevention of viral spreading . in our study , wearing of gloves by personnel was excellent ( 98% ) but they had a weak compliance rate with hand washing ( 58% ) .\nsimilar results have indicated in other studies [ 18 , 21 , 22 ] . in girou\nstudy , the rate of compliance with hand hygiene was 37% , and gloves were immediately removed after patient care in 33% .\nshowed that the dialysis staff adhered to hand washing and changing gloves in 57% before starting dialysis , in 55% between injections of medications to different patients , and in 47% when changing from one patient to another .\nmonitoring of viral markers is also essential for prevention of hepatitis viruses . in our study monitoring of hbv infection\nwas satisfactory but it was weak for hcv , especially at the center of province .\nbetter performance of hcp in other cities could be mainly due to low volume of patients and higher ratio of personnel to patients . according to cdc recommendations\nall hd patients should be screened and followed for hcv infection by anti - hcv , hcv pcr , and alt level determination . in the present study ,\nperiodic test of anti - hcv was performed in 69% of patients , but monthly assessment of alt and in case of high alt , pcr request , were the main defect points . in the 2002 survey of us\nattention to the primary education of personnel and regular annual retraining courses are the main steps in the elevation of performance of personnel in hemodialysis centers . in a study from sudan , although the knowledge of hcp about infection control measures in hd centers was good ( 81% ) but their performance in patients ' bed was weak ( 823% ) . in our study 4776% of personnel\nalthough there is a decreasing trend in the frequency of viral hepatitis in iran , it seems that still hd patients have a higher risk of infections mainly due to ignoring of safety measures to minimize the risk of transmission .\nemphasis on observance of standard infection control recommendations , retraining of hcp , and official supervision on performance of hd centers would be effective steps to reduce the viral transmission .", "answer": "introduction . noncompliance with the recommended infection control measures by the healthcare professionals ( hcps ) plays a major role in transmission of hepatitis b ( hbv ) and hepatitis c ( hcv ) viruses in hemodialysis ( hd ) wards . \n this study aimed to determine the compliance rate of the hcp with safety measures in the hd wards in southeast iran . \n patients and methods . a total of 208 patients were enrolled . \n adherence of hcps with standard infection control measures was assessed . \n results . \n sixty - one hcps with a mean age of 32.4 11.2 years old were responsible for healthcare services . \n compliance with the following items was weak : not sharing medications trolley ( 29.8% ) , disinfecting the shared instruments ( 46.2% ) , using single use materials for many patients ( 52.4% ) , carrying used materials in disposable containers ( 51.9% ) , not returning of unused materials to the clean room ( 55.3% ) , and adherence to hand washing ( 58.7% ) . \n periodic monitoring for hbv and hcv was performed on 100% and 69.7% of the patients , respectively . \n less than 2/3 of hcps participated in the retraining courses . \n conclusion . \n compliance of hcps with safety measures for viral hepatitis prevention was partly inadequate in hd wards . \n emphasis on retraining of hcps and official supervision would be effective steps in the reduction of viral dissemination .", "id": 300} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe chia ( salvia hispanica ) seed was used as an offering to the aztec gods , and , because of its religious use , it essentially disappeared for 500 years .\nthis is an annual herbaceous plant belonging to the lamiaceae or labiatae family . in pre - columbian times , it was one of the basic foods of several central american civilizations , less important than corn and beans , but more important than amaranth .\nthe chemical composition reports contents of protein ( 1525% ) , fats ( 3033% ) , carbohydrates ( 2641% ) , dietary fiber ( 1830% ) , and ash ( 4 - 5% ) .\nchia seeds have been investigated and recommended due to their high levels of proteins , antioxidants , dietary fiber , vitamins , and minerals but particularly due to their oil content with the highest proportion of -linolenic acid ( -3 ) compared to other natural sources known to date .\nchia seeds contain up to 39% of oil , which has the highest known content of -linolenic acid , up to 68% .\nchia seed gum has the potential for industrial use because of its slimy properties , evident even at very low concentration , and because the plant , native to america , grows well in semiarid regions that have few practical plants .\nchia gum begins to emerge from seeds as soon as they are placed in water .\nthe exudate is either partially cross - linked or is bound to the seed surface , since it is not easily separated from the seed .\nseparation can be accomplished by strong stirring , preferably in the presence of sand to aid in dislodgment or cleavage of insolubilizing bonds . for research purposes ,\ngum has been removed by extraction of seeds with a 6 m urea solution .\nchia gum is composed of -d - xylopyranosyl , -d - glucopyranosyl , and 4-o - methyl--d - glucopyranosyluronic acid unit in the ratio 2 : 1 : 1 . the polysaccharide seems to consist of a repeating unit .\nextracted gum has a slimy , mucilaginous character at very low concentrations , giving it wide potential use in a variety of industrial applications , especially in certain foods and food preparations .\nthe objective of the present study was to determine the physicochemical properties of fatted and defatted gums from chia ( salvia hispanica ) seeds .\nchia ( s. hispanica l. ) seeds were obtained in the yucatan state of mexico .\nreagents were of analytical grade and purchased from j. t. baker ( phillipsburg , nj , usa ) , sigma ( sigma chemical co. , st .\nlouis , mo , usa ) , merck ( darmstadt , germany ) , and bio - rad ( bio - rad laboratories , inc .\nseeds of chia were submitted to gum extraction with water at a 1 : 20 ratio ( w / v ) for 30 min and at a 50c temperature .\nafter that , the suspension was milled in a mixer and then it was boiled again at 50c under stirring for 15 min .\nthe crude mixture , containing water , gum , and seeds , was centrifuged at 9460 g at 15c for 3 h. the recovered gum ( fcg ) was dried at 40c for 24 hours and milled .\none portion of the recovered gum was partly defatted ( pdcg ) in a soxhlet .\nstandard aoac procedures were used to determine nitrogen ( method 954.01 ) , fat ( method 920.39 ) , ash ( method 925.09 ) , crude fiber ( method 962.09 ) , and moisture ( method 925.09 ) contents in the fatted and defatted chia gums .\napproximate water absorption capacity was first determined by weighing out 0.1 g ( d.b . ) of sample , adding water until saturation ( approximately 5 ml ) , and centrifuging at 2000 g for 10 min in a beckman gs-15r centrifuge .\napproximate water absorption capacity was calculated by dividing the increase in sample weight ( g ) by the quantity of water needed to complete original sample weight to 15 g. water absorption capacity ( wabc ) was then determined by placing samples in four tubes , adding different quantities of water to bracket the measurement ( 1.5 and 0.5 ml water above original weight and 1.5 and 0.5 ml water below ; one in each tube ) , agitating vigorously in a vortex for 2 min , and centrifuging at 2000 g for 10 min in a beckman gs-15r centrifuge .\naverage water absorbed was calculated and the wabc was calculated , expressed as g water absorbed per g of sample .\nbriefly , 0.1 g ( d.b . ) of sample was placed in an equilibrium microenvironment at 98% relative humidity , generated by placing 20 ml of saturated potassium sulfate saline solution in tightly sealed glass flasks and placing these in desiccators at 25c .\nthe sample was left in the microenvironment until reaching constant weight ( 72 h ) .\nbriefly , 0.1 g ( d.b . ) of sample was weighed and then stirred into 20 ml of distilled water or corn oil ( mazola , cpi international ) for one minute .\nthese fibrous suspensions were then centrifuged at 2200 g for 30 min and the supernatant volume was measured .\nwater - holding capacity was expressed as g of water held per g of sample , and oil - holding capacity was expressed as g of oil held per g of gum .\ncorn oil density was 0.92 g / ml . apparent viscosity was evaluated using an adaptation of the li and chang method , using a brookfield viscometer model dv - ii ( brookfield engineering lab . , stoughton , ma ) with spindle 27 ( for small samples ) and share rate range from 2.5 to 100 rpm at 25c .\nthe samples were dispersed in water to 0.5 , 1.0 , 1.5 , 2.0 , and 2.5% ( w / v , db ) .\nthe results were expressed in pa.s and data was fixed to an ostwald - de waele model to determine the consistency index ( k ) and flow behavior index ( n ) .\nthis percentage was lower than reported by sciarini et al . in gleditsia triacanthos seeds ( 11.934.16% ) .\nhowever , the chia gum 's yield was higher than reported by oomah et al . in flaxseed ( 3.68% ) .\nthe proximal composition ( table 1 ) showed that pdcg registered a higher content of protein , ash , and nfe than fcg .\nthe fiber content of fcg ( 28.96% ) was similar to that reported by vazquez - ovando et al . in a fiber - rich fraction of chia seeds ( 29.56% ) .\nthe moisture content of both gums was similar to that reported by kader et al . in acacia glomerosa ( 9.09% ) but lower than reported in guar gum ( 10.36% ) , xanthan gum ( 11.08% ) , and gleditsia triacanthos ( 14.08% ) .\nwith respect to the nfe content , both gums registered lower values than reported by vazquez - ovando et al . in a fiber - rich fraction of chia seeds ( 34.52% ) .\nhowever , the ash content of fcg and pdcg was higher than that reported by kader et al . in arabic gum ( acacia senegal , 3.6% ) although lower than reported by sciarini et al . in xanthan gum ( 9.35% ) .\nthe protein content of both gums was higher than registered in corn gum ( 5.1% ) and mesquite gum ( 5.8% ) , this last one with important emulsifying properties attributed to its protein content according to bosquez . in this respect ,\nestablish that hydrocolloids rich in protein , such as gelatin , arabic gum , and mesquite , are good stabilizers because they have sufficient hydrophobic groups to act as bonding points as well as hydrophilic groups that reduce surface tension in a liquid - liquid or liquid - gas interface . on the other hand , yadav et al . \nestablish that the lipid content in the gums may also play an important role in stabilization of oil - water emulsions .\nhowever , bosquez established that carbohydrates avoid flocculation and coalescence of oil droplets to extend in the aqueous solution .\nthese findings suggest that fcg and pdcg could act as good emulsifiers and stabilizers in the food industry . \n\nwater absorption capacity is indicative of a structure 's aptitude to spontaneously absorb water when placed in contact with a constantly moist surface or when immersed in water .\nwater adsorption capacity is the ability of a structure to spontaneously adsorb water when exposed to an atmosphere of constant relative humidity .\nwabc was higher in fcg ( 44.08 g / g of sample ) than pdcg ( 36.2 g / g of sample ) .\nthe high values of wabc obtained here could be due to the proteins present in the gums , which would have a large number of exposed hydrophilic sites interacting with water .\nthe wabc of fcg and pdcg was higher than reported by vzquez - ovando et al . in a fiber - rich fraction of chia seeds ( 11.73 g / g of sample ) , who establish\nthat fiber content is an important factor in the increment of this property for its capacity to form gels and to hold water ; this justifies the higher value of wabc in fcg .\non the other hand , pdcg ( 0.84 g / g of sample ) registered a higher value of wadc than fcg ( 0.27 g / g of sample ) .\nthe wadc of dcg was also higher than registered by vzquez - ovando et al . in a fiber - rich fraction of chia seeds ( 0.3 g / g of sample ) , similar to that reported in carrots ( 0.82 g / g of sample ) but lower than the value registered in beet bagasse ( 1.58 g / g of sample ) .\nhowever , whc of both gums was higher than that reported by vzquez - ovando et al . and baquero and bermdez in a fiber - rich fraction of chia seeds ( 15.41 g / g of fiber ) and passion fruit peel ( 8.7 g / g of fiber ) , respectively .\na similar behavior was observed with orange waste ( 7.658.23 g / g of fiber ) . soluble fiber and the denaturalized proteins\nmay have increased the whc of both gums , thus enhancing the swelling ability , an important function of proteins in preparation of viscous foods such as soups , gravies , dough , and baked products . on the other hand\n, fcg showed a higher ohc than pdcg , which might be related to its higher value of fat .\nhowever , both gums registered higher ohc values than those registered in guar and xanthan gum ( 46 g oil / g fiber ) although similar to that reported in arabic gum ( 8 - 9 g oil / g fiber ) .\nthis functional property has been attributed to the physical entrapment of oil for molecules such as lipids and proteins . for the above mentioned\n, the ohc registered in chia gums could be due to protein and fat contents as well as factors as particle size and the absence of hemicellulose .\nchia gum seems to possess an adequate fat absorption capacity , allowing it to play an important role in food processing , since fat acts on flavor retainers and increases the mouth feel of foods . \n\nboth gums showed a non - newtonian behavior where viscosity presented a relation directly proportional to the concentration and inversely proportional to the shear rate . the maximum viscosity reached between both gums\nwas registered by pdcg ( 55.4 pas ) at 2.5% . in general , pdcg registered a higher viscosity profile than fcg suggesting that the fat content was the principal factor that generated this behavior . at this respect ,\nreport that gums with higher oil absorption as arabic gum show less viscosity ( 2.34 pas at 3.8% ) . according to table 2 ,\nthe rheological behavior of the fcg and pdcg dispersions was a shear thinning or pseudoplastic type due to registered values of n < 1 .\nthe results suggest the use at low concentrations of dcg in products as yoghurts , sauces , toppings , and pastries among others that require high viscosity , whilst fcg could be used in sauces , mayonnaises , and meat products as emulsifying and stabilizer .\nthe results obtained here show that chia gums present interesting physicochemical properties for the food industry .\nthe partly defatted chia gum showed a very good ability to water holding ( 110.5 g / g ) ; however , their ability of oil holding ( 11.67 g / g ) and water absorption ( 36.26 g / g ) was minor compared to the fatted chia gum , which provided a greater retention of oil holding ( 25.79 g / g ) and water absorption ( 44.08 g / g ) .\nrheological behavior of gums was shear thinning or pseudoplastic type . from a functional point of view\n, chia gum also is an important food ingredient due its emulsifier and stabilizer potentials .", "answer": "chia ( salvia hispanica l. ) constitutes a potential alternative raw material and ingredient in food industry applications due to its dietary fiber content . \n gum can be extracted from its dietary fiber fractions for use as an additive to control viscosity , stability , texture , and consistency in food systems . \n the gum extracted from chia seeds was characterized to determine their quality and potential as functional food additives . \n the extracted chia gum contained 26.2% fat and a portion was submitted to fat extraction , producing two fractions : gum with fat ( fcg ) and gum partly defatted ( pdcg ) . \n proximal composition and physicochemical characterization showed these fractions to be different ( p < 0.05 ) . \n the pdcg had higher protein , ash , and carbohydrates content than the fcg , in addition to higher water - holding ( 110.5 g water / g fiber ) and water - binding capacities ( 0.84 g water / g fiber ) . \n the fcg had greater oil - holding capacity ( 25.7 g oil / g fiber ) and water absorption capacity ( 44 g water / g fiber ) . in dispersion trials , \n the gums exhibited a non - newtonian fluid behavior , specifically shear thinning or pseudoplastic type . \n pdcg had more viscosity than fcg . \n chia seed is an excellent natural source of gum with good physicochemical and functional qualities , and is very promising for use in food industry .", "id": 301} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrecurrent epithelial ovarian carcinoma has a poor prognosis and is almost always fatal [ 1 , 2 ] .\nthe most frequent relapse site involves the peritoneal cavity and the infradiaphragmatic lymph nodes . outside the abdomen ,\nthe most frequent metastatic sites are the pleura and the mediastinal lymph nodes [ 3 , 4 ] .\nalthough nodal metastases are well known in the course of epithelial ovarian carcinoma , solitary lymph node relapses are rarely described . the cervical , supraclavicular , groin and axillary areas are unusual sites of isolated lymph node involvement . in a retrospective study evaluating 640 ovarian cancer patients ,\nprognosis of isolated lymph node relapse seems better than that of metastatic recurrence at other sites and in the event of an asymptomatic relapse , immediate or delayed therapy should be assessed .\nrecurrence of ovarian carcinoma is commonly suspected when there is a progressive increase of the serum ca-125 level , but it does not allow differentiation between localized and diffuse tumor spread .\nct scan is the imaging technique of choice , but its capability to detect residual tumor is limited in case of small metastases , such as peritoneal , mesenteric and omental recurrences .\nf - fdg - pet can detect residual tumor with a higher accuracy than ct and even with a higher sensitivity than the tumor markers ca-125 [ 7 , 8 ] .\nrecently , we have observed internal mammary lymph node metastases diagnosed by f - fdg - pet / ct as a solitary recurrence site in 3 ovarian cancer patients .\na 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .\na pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .\n1a , b ) , with suspected infiltration of the right side of the sternum ( fig .\na ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .\nshe was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,\nthe serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .\nexternal radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .\npet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .\n6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007\n, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008\n, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .\nshe was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,\ndisease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .\na 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .\nsubsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments\n, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable . in absence of other signs of localizations ,\nthe patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .\nradiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .\nshe was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .\nno postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .\nshe was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,\nalmost 5 years later , the patient was well and showed no evidence of disease .\na 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,\n6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .\nthus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .\nfrom april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .\nthe serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .\na 65-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy , pelvic lymphadenectomy and omentectomy followed by chemotherapy ( carboplatin and cyclophosphamide ) for ovarian papillary serous adenocarcinoma stage ic in 1997 . at her annual followup , 9 years later ( may 2006 ) , the serum ca-125 level was increased ( 83 u / ml , normal value < 35 u / ml ) .\na pet / ct scan showed increased f - fdg uptakes in the bilateral internal mammary lymph nodes ( fig .\n1a , b ) , with suspected infiltration of the right side of the sternum ( fig .\na ct scan confirmed an abnormal left internal mammary lymph node of 1.7 cm in size and a thickening of the right parasternal tissue .\nshe was treated with 7 courses of chemotherapy ( carboplatin plus gemcitabine ) . at the end of the treatment ,\nthe serum ca-125 level was stable ( 75 u / ml ) and a ct scan confirmed stable disease .\nexternal radiation therapy was administered to the bilateral internal mammary lymph node chains at a total dose of 4,680 cgy .\npet / tc was performed 4 months after the end of the radiation therapy and showed a reduction of the f - fdg uptake in the right internal mammary lymph node ( suv max .\n6 vs. 11 ) and a complete normalization in the contralateral lymph node . in november 2007\n, she was retreated with chemotherapy ( 6 courses of carboplatin ) for disease progression in the internal mammary lymph nodes and the sternum . in july 2008\n, she developed 2 subcentimetric brain metastases that were treated with stereotaxic radiosurgery , obtaining a complete remission . in september 2008 , an increase of the serum ca-125 level occurred ( 265 u / ml ) and the ffdg - pet / ct scan showed multiple pathological uptakes in the supradiaphragmatic lymph nodes ( bilateral supraclavicular , internal mammary chains and mediastinal ) .\nshe was treated with 6 courses of carboplatin + paclitaxel and the serum ca-125 level was normalized . during 2010 ,\ndisease progression was further documented and monochemotherapy with pegylated doxorubicin was started . on december 31 , 2010 , she was still on treatment .\na 47-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and lombo - aortic lymphadenectomy followed by chemotherapy ( cisplatin and cyclophosphamide ) for ovarian papillary serous carcinoma stage iii in 1991 .\nsubsequently , she first received anterior sigmoid resection for pelvic relapse and adjuvant carboplatin ( 1996 ) , and secondly , chemotherapy with cisplatin + paclitaxel , followed by liver dissections for liver metastases and carboplatin + topotecan chemotherapy ( 1998 ) . during these treatments\n, there was no evidence of disease . in 2001 , at a follow - up examination , a right supraclavicular lymph node was palpable .\nin absence of other signs of localizations , she was treated with gemcitabine + vinorelbine over a 4-month period .\nthe patient experienced partial remission and subsequently , she was submitted for dissection of the right supraclavicular lymph node .\nradiation therapy was delivered postoperatively . in december 2002 , a pet / ct carried out during a follow - up examination , showed an increased f - fdg uptake in a left internal mammary lymph node ( fig .\nshe was operated on and a lymph node metastasis was removed and histologically confirmed ( poorly differentiated adenocarcinoma ) .\nno postoperative treatment was administered . in january 2006 , a pet / ct showed an increased f - fdg uptake in 3 supradiaphragmatic nodules located in the right anterior costophrenic sinus .\nshe was treated with supradiaphragmatic lymphadenectomy and partial diaphragm resection ; 3 out of 14 lymph nodes were massively infiltrated by a poorly differentiated adenocarcinoma of ovarian origin . at the last follow - up examination ( december 2010 ) ,\nalmost 5 years later , the patient was well and showed no evidence of disease .\na 51-year - old woman had been treated by total abdominal hysterectomy , bilateral salpingooophorectomy and omentectomy , followed by chemotherapy ( carboplatin and paclitaxel ) for ovarian papillary serous carcinoma stage iiib in 2002 . at her annual follow - up ,\n6 years later , the serum ca-125 level showed an increase above the normal level ( > 35 u / ml ) . a pet / ct scan revealed an increased ffdg uptake in the right internal mammary lymph nodes and the cardiophrenic nodule .\nthus , 1 month later , she was submitted for right internal mammarian lymphoadenectomy ; the histological examination confirmed a papillary adenocarcinoma .\nfrom april to july 2009 , she was treated with 6 courses of carboplatin and paclitaxel .\nthe serum ca-125 level was within the normal range . at the last follow - up visit , in september 2010 , she was well and showed no signs of recurrent disease .\nwe have been unsuccessful in finding reports on internal mammary lymph nodes metastases from ovarian cancer in the recent literature . in this case report , we have presented 3 cases of recurrent ovarian cancer in which pet / ct detected internal mammary lymph node metastases as unique site of disease , 6 , 9 and 11 years after the primary surgical operation , respectively . in the first and third case ,\npet / ct confirmed the recurrence suspected by the increase of the serum ca-125 level ; in the second case , pet / ct was carried out as a follow - up examination in absence of symptoms or increased serum ca-125 levels . in these 3 patients ,\nthe pet / ct scan has enabled a local therapeutic approach : a surgical treatment in two patients and radiation therapy in 1 patient , permitting a local control of the disease . at , respectively , 4.5 , 8 and 2 years after the diagnosis of internal mammary lymph node metastases our patients are still alive .\nto our knowledge , this is the first report on internal mammary lymph nodes as a site of late and very late solitary ovarian cancer recurrence and on the determining role of pet / ct scan for the diagnosis of isolated tumor involvement and therapeutic decisionmaking . surgical dissection or radical radiotherapy", "answer": "internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described . in this case report , \n 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented . \n 18f - fdg - pet / ct allowed the diagnosis which was suspected by the increase of the serum ca-125 level in 2 out of 3 cases . \n local treatment , consisting of surgery ( in 2 patients ) and radiation therapy ( in 1 patient ) , permitted an optimal long - term disease control .", "id": 302} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalong with the introduction of effective therapeutic agents such as somatostatin analogue ( ssa ) , multityrosine kinase inhibitor and mammalian target of rapamycin inhibitor , much improvement has been made in the treatment of neuroendocrine tumors ( net ) .\nespecially , the promid and radiant studies proved the effectiveness of these new therapeutic agents in the treatment of mid gut and pancreatic net , respectively .\nhowever , in the case of metastatic gastric net , there is neither an established treatment strategy nor a prospective study because gastric nets are not only rare but also mostly diagnosed in the early stage , which can be controlled by surgical resection .\ntherefore , gastric net has been considered a part of the gastroenteropancreatic net category and there have been no studies exclusively aimed at gastric net . in the treatment of metastatic net , a treatment approach according to the presence of hormonal symptom , embryological origin of primary site and pathologic grade is usually accepted as a principle . however , in the case of gastric net , a separate treatment approach depending on a specific classification , which can be recognized based on clinical and histologic characteristics , is considered . in the classification of gastric net , type\ni ( 74% of the gastric nets ) is associated with chronic atrophic gastritis and hypergastrinemia , and type ii ( 6% of the gastric nets ) is associated with multiple endocrine neoplasia type i , zollinger - ellison syndrome and hypergastrinemia .\nlastly , sporadic type iii gastric neuroendocrine carcinoma ( nec ; 13% of the gastric nets ) is gastrin - independent and carries the worst prognosis . in this paper\n, we describe the case of a female gastric net patient with multiple liver metastases who was unresponsive to biologic therapy and cytotoxic chemotherapy .\nin addition , we look at the therapeutic strategy for metastatic gastric net together with a literature review .\nupper endoscopic examination revealed a localized , fixed and firm subepithelial tumor ( diameter , 2.2 cm ) in the peripyloric area , but there was no evidence of gastric ulcer in the entire stomach ( fig .\na stomach computed tomography ( ct ) was performed and revealed two non - enhancing , low - attenuated liver masses in s4 ( 2.2 cm ) and s5 ( 1.6 cm ) suggesting metastasis ( fig .\nlaparoscopic antrectomy with gastrojejunostomy and liver biopsy were performed , but hepatic metastatectomy was not tried due to multiplicity .\nthe biopsy result of both gastric mass and metastatic hepatic nodule revealed a well - differentiated nec ( net g2 by 2010 who classification ) .\npathologically , the tumor was 37 21 mm in size with a negative margin ( distance from resected margin : 0.5 cm ) and infiltrated the muscular propria layer .\nmicroscopically , the tumor cells were medium - sized and uniform in shape and showed moderate cellularity with mild mitosis ( < 1/50 per high - power field ) ( fig .\non immunohistochemical staining , the tumor cells were positive for chromogranin a and cd56a ( fig .\n3d ) , and the serum gastrin level was increased to 1,832 pg / ml ( normal range 0108 ) . the vitamin b 12 level was 350 pg / ml ( normal range 211911 ) , chromogranin a level was 356.29 ng / ml ( normal range 2794 ) , 5-hydroxy indole acetic acid level was 3.04 mg / day ( normal range < 10 ) and serotonin ( 5-hydroxytryptamin ) was 48 ng / ml ( normal range < 200 ) .\nhowever , ct and mri did not localize any tumor assumed of gastrinoma . considering the gastrin level and histologic grade\nmoreover , she complained of abdominal pain with diarrhea and was therefore treated with long - acting repeatable ( lar ) sandostatin at a dose of 20 mg intramuscularly every 28 days .\nhowever , abdominal ct , which was performed 3 months later , revealed progression of the hepatic metastases without tumor recurrence in the operated bed ( fig .\nthe patient received an etoposide plus cisplatin ( ep ) combination chemotherapy ( etoposide 100 mg / m on days 13 , cisplatin 75 mg / m on day 1 ) . despite 3 cycles of ep chemotherapy , response evaluation identified a stable disease status , and eventually , her disease progressed after 6 cycles of ep chemotherapy ( fig . 2c ) . because of the patient 's economic situation and lack of grounds , targeted agents such as sunitinib and everolimus were infeasible .\ntherefore , we chose a combination therapy with interferon- ( ifn ) and sandostatin lar . on response evaluation after 3 months of treatment , she showed favorable response with regression of liver metastasis ( fig .\nsince oberndorfer first denominated the carcinoid tumor in 1907 , there has been much improvement in the classification and treatment of net .\nespecially the introduction of the new who pathologic classification system , which is based on the ki-67 labeling index and a few landmark studies such as promid and radiant , provided a useful guide to the oncologists dealing with gastroenteropancreatic net . based on these studies\n, ssa is known to be effective in the treatment of midgut nets , and cytotoxic chemotherapy such as the ep regimen is known to be effective in the treatment of foregut nets , including pancreatic nets .\nhowever , net can arise in most organs of the body and can show a variety of clinical features according to its origin and the degree of differentiation .\nmoreover , in the case of nets that originate from rare primary sites , standard treatment strategies have not been defined yet .\nalthough a division according to the embryological origin , which divides nets into foregut , midgut and hindgut nets , has been used in practice , it can not guarantee the homogeneity between the different organs inside the same embryological category .\nthat is to say , although gastric net embryologically originates from the foregut , we do not know exactly whether it shows an aspect similar to net of the pancreas .\nmoreover , gastric net has a few distinctive features in its pathogenesis and natural course .\ngastric net is known to be derived from the enterochromaffin - like ( ecl ) cells , which produce histamine , express the gastrin receptor and regulate gastric acid secretion .\ngastrin , which is released by g cells in the antrum of the stomach , duodenum and the pancreas , stimulate the release of histamine in ecl cells .\ntherefore , neoplastic changes in ecl cells are often associated with elevated serum gastrin levels . based on this unique pathogenetic background ,\na separate classification system for gastric net was first defined by rindi et al . in 1993 . according to this classification , gastric net\ncan be subdivided into types i , ii and iii , depending on the gastrin level and source of hypergastrinemia . a treatment strategy according to that system\nbecause of the relatively benign clinical course , low metastatic potential and low histologic grade of type i and ii gastric nets , the treatment strategy for these types of nets was focused on local control , and the principal treatment was conservative , including endoscopic follow - up or endoscopic mucosal resection . even in the case of multicentric tumor with liver metastasis , antrectomy and the consequent normalization of gastrin levels was considered sufficient for the control of the remnant lesion . as for medical treatment , biologic therapy such as ssa and ifn\na few studies also demonstrated a therapeutic value of octreotide in nets of gastroduodenal origin [ 6 , 7 ] . besides that , khuroo et al\n. showed that long - acting ssa injections reduced serum gastrin and serum chromogranin a levels with a 50% reduction in the visible number of tumors in 3 patients with type i metastatic gastric carcinoids .\nifn- and - have also been used in the treatment of gastrointestinal nets , regardless of functionality .\nimmune - mediated cytotoxicity , inhibition of progression of the cell cycle from the s to the g2 phase and inhibition of tumor angiogenesis were proposed as main mechanisms of ifn . however , systemic side effects such as flu - like symptoms and hypothyroidism hindered widespread usage as a first - line treatment . according to the european neuroendocrine tumor society ( enets ) guidelines , ssa is known to be valuable for the subgroups of patients with slowly progressive and low proliferative nets ( g1 ) of gastroduodenal origin , and in cases of metastatic g3 necs or well - differentiated but rapidly progressive metastatic disease , combinations of etoposide and cisplatin are recommended .\nhowever , it is not certain whether the histologic grade depending on the rate of cellular proliferation correlates with the classification based on gastrin levels and how to integrate the gastric net and who classifications into the same treatment strategy for gastric nets , especially in cases of metastatic disease .\nmoreover , there is the opinion that dysplastic cells are less dependent on gastrin stimulation and do not regress in response to reduced circulating gastrin levels .\nindeed , a few metastatic cases with a bad prognosis have been reported in type i or ii gastric nets [ 11 , 12 ] . in our case\n, the biopsy results showed a well - differentiated , g2 nec with 4% of ki-67 mitosis and an elevated gastrin level of 1,832 pg / ml .\nhowever , there was no evidence of endocrine neoplasia at the other site . based on the histologic grade and gastrin level , type\ntherefore , we expected good response to ssa , but somatostatin did not achieve response and disease progression was faster than expected .\nhowever , after 6 cycles of ep chemotherapy , the tumor eventually progressed within only 2 months . because the general condition of our patient was infeasible for another cytotoxic chemotherapy , we again used ssa for the relief of functional symptoms and stabilization of the tumor .\nin addition , we added ifn- and obtained favorable response . according to previous studies comparing ssa or ifn alone with a combination of the two drugs ,\nresponse was not superior in any of these groups , whereas the side effects leading to an interruption of the therapy were more frequent in the combination group .\nhowever , according to kolby et al . , the combination of ifn- and ssa reduced tumor progression better and for a longer time than either agent alone and was well tolerated because ssa can reduce side effects of ifn- , although the study was aimed at midgut net .\none review article about the combination of ifn- and ssa presented data showing an advantage of additional ifn- after progression following ssa alone .\nhowever , there is not enough statistical evidence for an upfront use of the combination of ifn- and ssa . in summary , for the treatment of metastatic gastric net , both the clinical classification according to the gastrin level and the pathologic grade should be considered .\nssa can be considered a first - line medical treatment for type i and ii metastatic gastric net .\nhowever , the combination of ssa and inf- can be an effective option in cases showing aggressive tumor behavior or after failure of ssa alone .", "answer": "despite remarkable progression in the treatment and classification system of neuroendocrine tumor ( net ) , some questions have remained unanswered . \n the lack of an established treatment strategy for gastric net is one of the problems . because of its paucity , gastric net \n is not discussed in independent , large - scaled prospective studies and tends to be excluded from clinical trials . \n moreover , a separate classification system and some distinguished clinical features render the treatment of gastric net more complicated . here , we present a case of a female gastric net patient with g2 proliferation index and multiple liver metastases . \n based on the histologic grade and a high serum gastrin level , we initially treated her with somatostatin analogue . \n however , the patient did not respond . \n after that , cytotoxic chemotherapy with the etoposide plus cisplatin regimen only showed response in the short - term period . \n however , combination therapy with octreotide and interferon brought about significant regression of the tumor . herein , we present our case together with a literature review of the treatment of metastatic gastric net .", "id": 303} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneuromyelitis optica ( nmo ) or devic 's disease is a rare inflammatory , demyelinating disease of the central nervous system ( cns ) that predominantly targets the optic nerves and spinal cord 1 . the disease was first described in 1870 by albutt and 24 years later , devic described the clinical characteristics of nmo \nthe discovery of a specific nmo immunoglobulin ( nmoigg ) opened a new era in the classification and understanding of the pathogenesis of nmo 3 .\nnmoigg binds to aquaporin4 , which is the main channel that regulates water homeostasis in the cns .\ndiagnostic criteria for nmo with aquaporin4 antibodies ( aqp4ab ) requires at least one core clinical characteristic , a positive test for aqp4ab using best available detection method ( cellbased assay recommended ) and exclusion of alternative diagnoses 1 .\nthe core clinical characteristics are , for example , optic neuritis , acute myelitis , acute brainstem syndrome , symptomatic narcolepsy , or symptomatic cerebral syndrome with typical nmo brain lesions 1 .\nneuromyelitis optica must be distinguished from other demyelinating diseases , for example , multiple sclerosis .\nthe presence of aqp4ab differentiates nmo from multiple sclerosis ( ms ) with high specificity 4 .\nin contrast to typical ms , the clinical events in nmo are usually more severe 5 , 6 .\ncerebrospinal fluid ( csf ) findings in nmo are also known to differ significantly from those in classical ms . csfrestricted oligoclonal igg bands are absent in most nmo patients .\nhowever , pleocytosis is usually mild , and frequently includes neutrophils , eosinophils , activated lymphocytes , and/or plasma cells 6 , 7 .\nstudies carried out in europe , south east and southern asia , the caribbean and cuba suggest that the incidence and prevalence of nmo ranges from 0.050.4 to 0.524.4 per 100,000 , respectively 9 .\nthe disease is mainly sporadic , although a few familial cases have been reported 10 .\nwe describe a case of an unusual and severe course of nmo affecting almost the entire spinal cord and brain .\nexamination on the day of admission revealed normal results as regards ecg , troponin i , and computed tomography ( ct ) of the chest and abdomen .\nthe next day , the patient reported headache and neurological examination showed rightsided hemiparesis and afferent pupillary defect of the left eye suggesting an afferent optic nerve defect . within a few hours , the patient showed a rapid neurological deterioration with progressive tetraplegia and global decline .\nmri of the spinal cord showed myelitis in the spinal cord segments c2 to th5 ( fig .\ncsf examination revealed polymorphonuclear pleocytosis ( leukocytes 1210 10/l , neutrophils 95% ) and an increased total protein concentration ( 2273 mg / l ) .\ndue to spinal cord mri and csf findings , infectious transverse myelitis could not be excluded and the patient was treated with dexamethasone , acyclovir , ceftriaxone , ampicillin , and levofloxacin .\n( a ) sagittal t2fse mri of the spinal cord showing high signal changes . ( b )\naxial t2flair brain mri showing high signal changes in thalami , internal capsule , and corpus callosum .\n( c ) axial t2flair brain mri showing high signal changes in pons , medulla oblongata , cerebellum , and middle cerebellar peduncle .\nthe next day , the patient 's condition worsened ; she became comatose and had a respiratory failure that required assisted ventilation ; this might be caused by bilateral phrenic nerve involvement as its roots originate from c3 to c5 where the lesion was also seen ( fig .\nbrain mri showed high signal changes in thalami , internal capsule , and corpus callosum ( fig .\n1b ) and also similar changes in pons , medulla oblongata , cerebellum , and middle cerebellar peduncle ( fig .\ntreatment with methylprednisolone and immunoglobulin was attempted and as serum aqp4ab was confirmed as positive ( indirect immunofluorescence assay was used , the titer was 19.85 , normal < 10 ) and the patient did not respond to the treatment , the patient was also treated by means of plasmapheresis .\nhistological examination of the cns revealed extensive , sharply limited demyelination and axon defect ( fig . 2a and b ) .\nthe spinal cord was almost entirely affected . only the lumbar area was partly spared .\nsmaller demyelination foci were found in the periventricular area of the hippocampus and in the corpus callosum .\ndemyelination was verified by showing both cd68positive macrophage infiltration and betaapp positivity as signs of axonal damage .\n( b ) the axon defect is shown by immunostaining ( brown staining ) of betaamyloid precursor protein ( app ) .\nthis is the first case report of nmo described from finland from the aqp4ab era .\nthere is only one older publication of a finnish nmo patient from the preaqp4antibody era 11 .\nthe patient was referred to hospital with an acuteonset chest pain , which is an unusual first symptom of nmo .\ndemyelination affected almost the entire spinal cord , sparing only partly the lumbar cord , which is unusual at first myelitis .\nlesions involving the lumbar or sacral spinal cord in addition to the cervical and thoracic portions have been reported only in 11% of patients at first myelitis .\nprevious reports have revealed that 92% of the patients have at least one spinal cord lesion extending over three or more vertebral segments at their first myelitis .\nit has been reported that seropositive women have more severe clinical attacks than males , as evidenced by high lesion load in the spinal cord and other types of coexisting autoimmunity 6 .\nbrain mri abnormalities are relatively common and may be relatively unique by virtue of localization and configuration 12 , as seen also in our patient .\nthe histopathological findings in the cns , csf , and aqp4ab seropositivity are consistent with neuromyelitis opticatype demyelination , although the disease course of our case was not typical of nmo due to its rapid and severe course . according to hospitalbased observational studies , mortality of nmo ranges from 2.9% to 25% and\nreported that disease duration at the time of death ranged from 6 months to 23.6 years 6 .\nin addition , our patient 's histological examination revealed extensive , sharply limited demyelination of the spinal cord and brain in the acute phase of the disease . to the best of our knowledge ,\nthe treatment in this particular case was targeted to multiple causes of the symptoms due to the unknown etiology in the beginning of the disease .\nacute attacks and relapses of nmo are generally treated with intravenous glucocorticoids followed by plasmapheresis for refractory or progressive symptoms 13 , 14 .\nhowever , there are no controlled trials evaluating the treatment of nmo , and recommendations are primarily supported by data from observational studies and by the clinical experience of experts . despite several forms of treatment , the patient did not survive .", "answer": "key clinical messageneuromyelitis optica is a rare inflammatory , demyelinating disease of the central nervous system that predominantly targets the optic nerves and spinal cord . \n our case represents an unusual and severe course of neuromyelitis optica . despite several forms of treatment \n , our patient died after a severe and shortterm attack .", "id": 304} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nDirect Amination of \\xce\\xb1-Hydroxy Amides\n\nPaper sections:\n\n\u03b1-Amino amides are very important molecules that are widely used in organic and medicinal chemistry. They are present in many drugs, such as Leukotriene D4, Safinamide, Lidoderm, Altace, Indinavir, Vyvanse, and in all aminopenicillins. They are also present in many natural products, such as canthiumine, coelichelin,[1] zorbamycin,[2] guadinomine B,[3] myrianthine B,[4] abyssenine,[5] paliurine E,[5] and mucronine J.[6] Moreover, \u03b1-amino amides are used as building blocks for the synthesis of different molecules and scaffolds like hydantoins.[7] Recently, the use of \u03b1-amino amides as organocatalysts for various asymmetric reactions has proven to be an extremely valuable approach owing to their facile structural modification and accessibility.[8]
Tremendous progress has been made in the use of C\u2013N bond formation for direct amination reactions.[9] Recently, more efforts have been focused on the direct amination of alcohols by using transition metals or Lewis acids (Scheme 1, method A).[9\u201310] These protocols improved the waste balance and are a powerful tool for the C\u2013N bond formation. This approach is also strongly preferred in industry, and more research in this field is desirable.[11]
Despite good progress in this field, the scope of alcohols and amines is largely restricted. Moreover, these approaches are not valid for more complex structure like \u03b1-hydroxy amides, and also for inactivated amines, where reaction typically proceeds with poor yield. Direct amination of the \u03b1-hydroxy amide is more challenging than the alcohol, as the amide group could hinder the coordination sites on the catalyst to resist direct amination. Therefore, finding a new method for the direct amination of \u03b1-hydroxy amide to gain access to highly important \u03b1-amino amides remains an important challenge.
Conversely, to the best of our knowledge, there is only one report by Beller and co-workers for the direct amination of \u03b1-hydroxy amides (Scheme 1 method B).[12] They used a ruthenium-catalyzed \"borrowing-hydrogen\" process for the direct amination. This protocol is simple and green, but it involves the use of a costly catalyst and ligands. Moreover, high reaction temperatures and a limited substrate scope were major disadvantages.
Here, we are reporting a TiCl4-assisted, general, economical, base/ligand-free mild method for the direct amination of \u03b1-hydroxy amides. The method is distinguishable by its wide scope, which includes primary, secondary and heterocyclic amines, and even indole and a primary amide.
We started our optimization by screening different Lewis acids, as Lewis-acid-activated reactions are well-developed for the direct amination of alcohols, when used in catalytic and stoichiometric amounts.[9\u201310] We sought to examine the possibility of these economical and non-toxic Lewis acids for the direct amination of \u03b1-hydroxy amides. We evaluated different Lewis acids, such as InCl3, ZnCl2, ZrCl4, GdCl2, Sc(OTf)3, TiCl4, and FeCl3, in a catalytic amount at room temperature in 1,2-dichloroethane (DCE); however, a trace of the target product was only observed when using TiCl4. Next, we increased the temperature and catalyst amount of TiCl4. Ultimately, we found that increasing the temperature to 100 \u00b0C, and a stoichiometric amount of TiCl4, product formation slightly improved. Then, we screened different solvents with 1 equivalent of TiCl4 at 100 \u00b0C (Table 1). In DCE, a low amount of the desired amination product 3a was observed together with a significant amount of starting material (Table 1, entry 1). The reaction did not reach completion even after three days. With further solvent screening, the coupling product yield improved remarkably up to 62% in solvents, such as 1,4-dioxane, toluene, and THF (Table 1, entries 2\u20134). The reaction in methanol did not proceed at all. In CH2Cl2, a lower product yield (53%) was observed. Further improvement was observed when acetonitrile was used as a solvent, affording the product in excellent yield (85%, Table 1, entry 7). The reaction did not reach completion with xylenes or DMF even after three days.
Aiming to get a higher yield, we turned our attention toward the use of different additives,[9\u201310] such as bases (KOH and triethylamine) or drying agents (molecular sieves and MgSO4). With these additives, the reaction became slow and did not finish even with longer reaction times, with starting materials remaining unreacted in substantial amounts \u224850\u201360%. Next, we performed equivalence studies of the amine morpholine and we found that 1 and 2 equivalents of morpholine formed only 23 and 42% product, respectively. When the TiCl4 equivalents were reduced to 20 mol%, no product was formed. However, when using 50 mol% TiCl4, some product was formed (39%), but the reaction remained incomplete even after three days at 130 \u00b0C. In conclusion, the optimal conditions for this reaction were 100 \u00b0C with 1 equivalent of TiCl4 in MeCN.
With these optimized conditions in hand, we examined the scope and limitations of this TiCl4-mediated amination reaction (Scheme 2). Alkylamines like allylamine, cyclohexylamine, and benzylamine effectively worked, forming the corresponding products in good yields (68, 76, and 83%, respectively).
Arylamines worked well (3e and 3f). Electron-donating and electron-withdrawing substituents on the arylamines were compatible with the reaction, leading to the desired products in good to moderate yield (3g and 3h). Moreover, we expanded the scope of the reaction to heterocyclic amines. Heteroaryl molecules are very important in drugs, as these molecules are present in almost half of the top 200 drugs.[13] Heterocyclic amines like pyrimidine, benzothiazole and benzimidazoles are known to be inactivated amines; however, they can be used in this protocol, providing good yields of 58, 84 and 69%, respectively (3i\u20133k).
Next, we screened different secondary amines, including cyclic amines like piperidine and thiomorpholine 1,1-dioxide, which also proved to be good substrates. The reaction with indole also provided the product in 36% isolated yield. The low yield owed to incomplete conversion, although the reaction was carried out for three days at 130 \u00b0C and up to 3 equivalents of TiCl4. The method also worked for a primary amide, butyramide, to form bis-amide product 3p, in low 15% yield, while recovering mostly starting material (>50%).
Finally, we extended the scope of the reaction to differentially substituted \u03b1-hydroxy amides. As expected, other \u03b1-hydroxy amides derivatives also showed similar results. Aliphatic and aromatic amides, and the heterocycle thiophene also worked well. The product of thiophene-substituted \u03b1-hydroxy amide with morpholine 3q was produced in 70% yield. Aliphatic derivatives 3r and 3s formed their corresponding products in moderate yields of 62 and 59%, respectively, as the reaction remained incomplete.
Previously, TiCl4-assisted substitution reactions were reported to proceed through a carbocation mechanism.[14] Other groups described TiCl4-catalyzed nucleophilic substitutions of alcohol that proceeded via carbocation formation followed by nucleophilic attack.[14a,15] Studies on the detailed mechanism of this direct amination of \u03b1-hydroxy amides are now underway.
In summary, we developed a TiCl4-facilitated, ligand/additive-free relatively mild reaction for the direct amination of \u03b1-hydroxy amides. Under the optimized reaction conditions, a broad range of amines including primary, secondary and heterocyclic amines, and even primary amides and indoles were found to participate in this transformation, providing the products in moderate to high yields. Different \u03b1-hydroxy amides containing aliphatic, aromatic or heterocyclic substituents such as thiophene also worked well.
", "answer": "A TiCl4-mediated reaction for the direct amination of \\xce\\xb1-hydroxy amides has been developed. This simple, general, additive/base/ligand-free reaction is mediated by economical TiCl4. The reaction runs under mild conditions. This highly efficient C\\xe2\\x80\\x93N bond formation protocol is valid for diverse amines, including primary, secondary and heterocyclic amines, and even a primary amide and indole.", "id": 305} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npapillon - lefevre syndrome belongs to a heterogeneous group of skin diseases that are characterized by hyperkeratosis of palms and soles .\npapillon - lefevre syndrome is inherited as an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and early loss of primary and permanent teeth .\npapillon - lefevre syndrome differs from other types of palmoplantar keratoderma in its severe periodontopathy and premature loss of primary and permanent dentition .\npapillon - lefevre syndrome was first described in 1924 by papillon m m and lefevre p in two siblings .\nfifty percent of the patients with papillon - lefevre syndrome appear to have been derived from consanguineous marriages .\nhart et al . , showed that mutations of cathepsin c gene are responsible for papillon - lefevre syndrome and a region of chromosomes ( 11q14 - 21 ) is responsible for this .\nan 18-year - old boy reported to the department of periodontology and implant dentistry , bharati vidyapeeth university dental college and hospital , navi - mumbai for the treatment of generalized mobility of teeth and bleeding gums .\nscaly skin lesions began to appear by third year of age , later fissures appeared on palms and soles .\nintense itching was noted and skin lesions went on to involve fingers , knees and elbows .\npatient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .\nintraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .\nhyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1 this patient too showed considerable hyperkeratosis of palms and soles [ figure 6 ] .\northopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .\nhyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,\nthorough scaling and root planing of all teeth was carried out along with administration of systemic antibiotics .\npatient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .\nintraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .\nhyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1 this patient too showed considerable hyperkeratosis of palms and soles [ figure 6 ] .\northopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .\nhyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,\npatient showed bilateral hyperkeratosis of palms , soles , dorsal surface of fingers and knees [ figures 1 and 2 ] .\nintraoral examination showed that the patient had lost most of his permanent teeth and the remaining teeth showed grade ii mobility .\nhyperkeratosis of palms and soles - case 1 hyperkeratosis of knees - case 1 intra - oral view - maxilla - case 1 intra - oral view - mandible - case 1\northopantomograph showed moderate horizontal bone loss and erupting permanent tooth buds [ figures 79 ] .\nhyperkeratosis of palms and soles - case 2 intra - oral view - maxilla - case 2 intra - oral view - mandible - case 2 complete blood count , serum calcium and alkaline phosphatase levels were done for both patients and were found to be within normal limits . on the basis of history ,\nthorough scaling and root planing of all teeth was carried out along with administration of systemic antibiotics .\npapillon - lefevre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis .\nskin lesions develop concurrently with oral lesions and may extend to dorsal surfaces of hands and feet .\nanother form of disease associated with palmoplantar keratosis and severe aggressive periodontitis has been named haim - munk syndrome .\nit differs from papillon - lefevre syndrome in symptoms such as arachnodactyly , acroosterolysis and onychogryphosis . in papillon - lefevre syndrome\nthe permanent dentition starts to erupt at proper time , but around 8 - 9 years of age periodontal destruction is repeated in the same manner as in primary dentition .\nall permanent teeth are usually lost before 14 - 16 years of age . in subjects with papillon - lefevre syndrome\nthe exact biochemical defect leading to periodontal disease is still unclear . in 1942 , wannenmacher suggested that papillon - lefevre syndrome was due to a combination of ecto and mesodermal malformations .\nsuggested that a functional imbalance of collagenolytic activity in the periodontal ligament was responsible for periodontitis in papillon - lefevre syndrome . in 1984 , vandyke suggested that neutrophils from an individual with papillon - lefevre syndrome exhibit decreased receptor affinity for chemotaxins such as formyl peptides .\npapillon - lefevre syndrome is associated with myeloperoxide deficiency , low integrin expression , defective phagocytosis and chemotaxis .\nhattab et al . , reported four cases of papillon - lefevre syndrome affecting two jordanian families with eight children . in all patients there was a relationship between increased severity of skin lesions and seasonal variations and intensified periodontal destruction .\nlass et al . in three multiplex families , one ethiopian and two german , demonstrated linkage of papillon - lefevre syndrome with chromosome 11q13-q14 .\nfischer et al . , conducted a primary genome wide search by homozygosity mapping in a large consanguineous family with four affected siblings .\ntoomes et al . , showed that in patients with papillon - lefevre syndrome gene for cathepsin c which lies in chromosome 11 had undergone mutation resulting in decreased cathepsin c production .\nhart et al . , reported mutations in cathepsin c gene in patients with papillon - lefevre syndrome from five different countries . in conclusion , we have reported two cases of papillon - lefevre syndrome .\nfurther studies in the field of microbiology and genetics are necessary to find the exact cause of periodontal destruction in such patients , so that best possible dental treatment can be rendered to them .\nin subjects with papillon - lefevre syndrome there is defective cathepsin c production . the gene for cathepsin c lies on chromosome 11 .\nthe exact biochemical defect leading to periodontal disease is still unclear . in 1942 , wannenmacher suggested that papillon - lefevre syndrome was due to a combination of ecto and mesodermal malformations .\nsuggested that a functional imbalance of collagenolytic activity in the periodontal ligament was responsible for periodontitis in papillon - lefevre syndrome . in 1984 , vandyke suggested that neutrophils from an individual with papillon - lefevre syndrome exhibit decreased receptor affinity for chemotaxins such as formyl peptides .\npapillon - lefevre syndrome is associated with myeloperoxide deficiency , low integrin expression , defective phagocytosis and chemotaxis .\nhattab et al . , reported four cases of papillon - lefevre syndrome affecting two jordanian families with eight children . in all patients there was a relationship between increased severity of skin lesions and seasonal variations and intensified periodontal destruction .\nlass et al . in three multiplex families , one ethiopian and two german , demonstrated linkage of papillon - lefevre syndrome with chromosome 11q13-q14 .\nfischer et al . , conducted a primary genome wide search by homozygosity mapping in a large consanguineous family with four affected siblings .\n. toomes et al . , showed that in patients with papillon - lefevre syndrome gene for cathepsin c which lies in chromosome 11 had undergone mutation resulting in decreased cathepsin c production .\nhart et al . , reported mutations in cathepsin c gene in patients with papillon - lefevre syndrome from five different countries . in conclusion ,\nfurther studies in the field of microbiology and genetics are necessary to find the exact cause of periodontal destruction in such patients , so that best possible dental treatment can be rendered to them .", "answer": "papillon - lefevre syndrome is a rare ( 1 - 4 cases per million ) autosomal recessive disorder showing predominantly oral and dermatological manifestations in the form of aggressive periodontitis affecting both primary and permanent dentition and palmoplantar hyperkeratosis . \n genetic studies have shown that mutations in the major gene locus of chromosome 11q14 with loss of function of cathepsin c gene are responsible for papillon - lefevre syndrome . \n this report presents two siblings with classic signs and symptoms of papillon - lefevre syndrome . \n the exact cause for periodontal destruction in patients with papillon - lefevre syndrome is not known but it is thought to be due to defect in neutrophil function , immune suppression and mutations in cathepsin c gene .", "id": 306} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalpha ( )2-adrenoceptor agonists have been used as adjuvant to anesthetic agents in peri - operative period for its several beneficial actions . these drugs improve hemodynamic stability during endotracheal intubation and surgical stress by its central sympatholytic action , and thus reduce anesthetic and opioids requirements .\ndexmedetomidine , the pharmacologically active d - isomer of medetomidine , is highly selective and specific 2-adrenoceptor agonist .\nthe analgesic effect of dexmedetomidine is qualitatively different as compared to opioids and can be used as an alternative to opioids in general anesthesia .\nthe anesthetic sparing effect of dexmedetomidine demonstrated in earlier studies is confounded by the use of opioids .\nopioids , when used as analgesic in general anesthesia , are known to decrease mac value of sevoflurane .\ninhalation agents were titrated based on either hemodynamic criteria and/or bispectral index values in studies done earlier , and none of them demonstrated the effect of dexmedetomidine alone on requirement of sevoflurane with the use of entropy as a measure of depth of anesthesia .\nthe primary objective of our study was to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on sevoflurane requirement during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis .\nthe study protocol was approved by ethical committee of the institute , and written informed consent was obtained from all patients included in the study .\nthe study population comprised of 60 patients , aged 18 - 55 years , with american society of anesthesiologists ( asa ) status of 1 and 2 , undergoing major elective surgical procedures .\nwe excluded patients older than 55 years , those with a history of psychiatric / neurological illness , cardiovascular disease , hypertensive patients , morbid obese patients , pregnant and nursing women , with known allergic reaction to any of the study medication , recent use of sedatives or analgesics , and with significant laboratory abnormalities .\nthe consenting patients were randomly allocated into one of the two anesthetic groups based on the simple randomization table generated : group a ( control group ) : sevoflurane - fentanyl and group b ( test group ) : sevoflurane - dexmedetomidine .\nafter arrival in the operating room , glycopyrrolate 0.004 mg / kg and ondansetron 0.15 mg / kg intravenous ( iv ) were given as pre - medication in both the groups .\nthe patients in group b received dexmedetomidine(2 ml diluted in 48 ml of saline ) iv in a dose of 1 mcg / kg over10 minutes through infusion pump prior to induction .\nmonitoring consisted of continuous electrokardiogram ( ekg ) , non - invasive blood pressure ( nibp ) , pulse oximetry ( spo2 ) , co2 expired fraction ( etco2 ) , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and electroencephalograph ( eeg ) analysis by entropy ( response and state entropy ) . after the start of drug infusion , heart rate ( hr ) , blood pressure\n( bp ) , respiratory rate ( rr ) , spo2 , and entropy were measured at 5 and 10 minute .\npatients in group a received fentanyl 2 g / kg intravenous slowly , 2 minutes prior to induction .\nafter pre - oxygenation for 10 minutes , general anesthesia was induced with thiopentone sodium 5 mg / kg iv slowly .\n, dexmedetomidine infusion was continued between 0.2 and 0.8 mcg / kg / h depending on hr , bp , and entropy value changes .\nanesthesia was maintained with sevoflurane to a maximum of 2.5% end tidal to maintain heart rate and blood pressure within 20% of baseline value and entropy value between 40 and 60 .\nthe anesthesiologist was permitted to treat hemodynamic events , defined as heart rate and blood pressure more than 20% of baseline , in spite of increasing sevoflurane concentration to 2.5% and dexmedetomidine infusion to 0.8 mg / kg with supplemental analgesia in the form of fentanyl 1 mcg / kg . if rise in heart rate and blood pressure persisted further after supplementation with fentanyl , anesthesiologist was permitted to administer incremental doses of metoprolol 2 - 5 mg .\nephedrine 5 mg iv was given for fall in heart rate and blood pressure more than 20% of baseline .\nin the group b , dexmedetomidine was stopped approximately 15 - 20 minutes before completion of surgery , diclofenac sodium aqueous 1 mg / kg was given iv in both groups at the time of skin closure .\nreversal of neuromuscular blockade was achieved with neostigmine 0.05 mg / kg and glycopyrrolate 0.008 mg / kg iv slowly .\ntracheal extubation was done when respiration was satisfactory and adequate muscle tone was achieved . \n\nhr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.depth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.end tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis . \n \nhr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .\ndepth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .\nend tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis .\nstatistical analysis was conducted with epi info software ( version 3.5.3 , 2011 , centers for disease control and prevention , atlanta , ga , usa ) for windows statistical package using unpaired t - test for continuous variables with normal distribution .\nthe non - parametric kruskal - wallis test was used for variables not normally distributed . for categorical variables , chi - square test was used .\nthe two groups were similar regarding age , sex , weight , and asa physical status [ table 1 ] .\npre - induction heart rate , systolic and diastolic blood pressures were similar between two groups ( p > 0.05 ) .\nthe depth of anesthesia as assessed by response entropy ( re ) and state entropy ( se ) was comparable between two groups at all time points during maintenance period ( p > 0.05 ) .\nthe re and se was maintained between 40 and 60 during the period of observation .\nthe fisevo concentration was significantly less in group b as compared to the group a at all time points ( p < 0.05 ) [ figure 1 ] .\nthe average etsevo concentration during anesthetic maintenance was 1.35% and 1.72% in the group b and a , respectively .\na significant decrease of 13% to 33% of etsevo concentration was seen with group b from 5 min to 60 minutes post - intubation ( p < 0.05 ) during surgery [ figure 2 ] .\nfraction of inspired sevoflurane at different time interval ( pi - post - intubation , fi - fraction of inspired ) end tidal sevoflurane at different time intervals ( pi - post - intubation ) during anesthesia maintenance , group b showed a statistical significant decrease in heart rate , systolic and diastolic blood pressure from baseline at all time points as compared to the group a ( p < 0.05 ) .\nan average 6.5% fall in heart rate from baseline in group b as compared to 3.7% rise in the group a , 8% fall in systolic blood pressure from baseline as compared to 3.6% rise in the group a , and 8.16% fall in diastolic blood pressure from baseline as compared to 3.3% rise in the group a was observed [ figures 3 and 4 ] .\nchanges in sbp and dbp at various time points post - intubation ( pi - post - intubation , sbp - systolic blood pressure , dbp - diastolic blood pressure ) changes in hr at various time points post - intubation ( pi - post intubation , hr - heart rate ) in our study , none of the patients in either group required supplemental analgesia or anti - hypertensive drugs intra - operatively .\nbradycardia was observed in 2 patients in group b within 10 mins post - extubation , which promptly responded to atropine 0.6 mg iv .\nthe major observation in our study was that dexmedetomidine infusion as an adjuvant in general anesthesia causes decreased requirement of sevoflurane without compromising adequate depth of anesthesia , thus it has anesthetic - sparing property .\na study done on patients undergoing hysterectomy showed a 30% reduction of maintenance concentration of isoflurane .\nsimilarly , a reduction in 35% to 50% in isoflurane concentration with low or high dose of dexmedetomidine was found in a study on healthy human volunteers .\nthis larger reduction in isoflurane requirement seen as compared to our study might be due to difference in study population ( healthy human volunteers vs. patients posted for elective surgery ) and the type of stimulus ( tetanus nerve stimulus vs. surgical stimulus ) .\nthe results of our study results are consistent with that of the study done by fragen , et al . in elderly patients , which showed a 17% reduction .\ndexmedetomidine by its sympatholytic action decreases heart rate and blood pressure , thus assessing the depth of anesthesia by hemodynamic parameters would be unreliable in evaluating its effect on requirement of inhalational agent . several electroencephalogram - dependent indices such as bispectral index and entropy have been used to measure the depth of anesthesia .\nentropy is a useful monitor for measuring the electroencephalographic effects of increasing and decreasing sevoflurane concentration and assessing the depth of anesthesia .\nanalogous to the bispectral index , entropy displays a high degree of specificity and sensitivity in assessing consciousness during anesthesia . using bispectral index to assess the depth of anesthesia , magalhes et al\n. showed decreased requirement of sevoflurane with continuous infusion of dexmedetomidine during general anesthesia . in our study , we used entropy to measure the depth of anesthesia , thereby eliminating the bias of evaluation by hemodynamic parameters as in earlier studies .\nuse of dexmedetomidine produces intra - operative and post - operative opioids - sparing effect .\ndexmedetomidine by its sympatholytic action attenuates symapthoadrenal response to tracheal intubation . in patients undergoing laparoscopic tubal ligation , a 33% decrease in morphine\nuse post - operatively was observed when dexmedetomidine was used at a dose of 0.4 mcg / kg .\ndexmedetomidine when administered as infusion at a dose of 0.5 mcg / kg / h has specific analgesic effect and provides visceral pain relief . in morbidly obese ,\ndexmedetomidine produces a greater decrease in sympathovagal balance intra - operatively than fentanyl along with better post - operative analgesia .\ndexmedetomidine , when used as sole substitute for remifentanil in ambulatory gynecologic laparoscopic surgery , provides better peri - operative hemodynamic stability and post - operative analgesia .\ndexmedetomidine provides similar intra - operative hemodynamic response and better post - operative analgesia compared to remifentanil in patients undergoing supratentorial craniotomy .\nuse of opioids along with dexmedetomidine would confound its effect on requirement of inhalation agent .\nhence , in our study , fentanyl was not administered in dexmedetomidine group b , and we found a 21.5% decrease in the etsevo , in contrast to 33.12% decrease in study done by magalhes e et al . where fentanyl was used .\none limitation of our study was that we included both laparoscopic as well as open surgeries .\nto conclude , the continuous infusion of dexmedetomidine , as adjuvant in general anesthesia , significantly decreases the requirement of sevoflurane for maintaining adequate depth of anesthesia .\nstudies measuring plasma concentration of dexmedetomidine should be undertaken to establish the precise correlation between its dose and inhalational agent 's requirements .", "answer": "background : dexmedetomidine , a 2 agonist as an adjuvant in general anesthesia , has anesthetic and analgesic - sparing property.aims:to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on requirement of sevoflurane during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis.materials and methods : sixty patients were randomly divided into 2 groups of 30 each . in group \n a , fentanyl 2 mcg / kg was given while in group b , dexmedetomidine was given intravenously as loading dose of 1 mcg / kg over 10 min prior to induction . \n after induction with thiopentone in group b , dexmedetomidine was given as infusion at a dose of 0.2 - 0.8 mcg / kg . \n sevoflurane was used as inhalation agent in both groups . \n hemodynamic variables , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and entropy ( response entropy and state entropy ) were continuously recorded . \n statistical analysis was done by unpaired student 's t - test and chi - square test for continuous and categorical variables , respectively . \n a p - value < 0.05 was considered significant.results:the use of dexmedetomidine with sevoflurane was associated with a statistical significant decrease in etsevo at 5 minutes post - intubation ( 1.49 0.11 ) and 60 minutes post - intubation ( 1.11 0.28 ) as compared to the group a [ 1.73 0.30 ( 5 minutes ) ; 1.68 0.50 ( 60 minutes ) ] . \n there was an average 21.5% decrease in etsevo in group b as compared to group a.conclusions:dexmedetomidine , as an adjuvant in general anesthesia , decreases requirement of sevoflurane for maintaining adequate depth of anesthesia .", "id": 307} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninsulin detemir has now become established as an effective basal insulin preparation and is widely used in the management of both type 1 and type 2 diabetes . although it is similar in efficacy to isophane insulin , we have observed a relative lack of efficacy in two patients with significant hypertriglyceridemia and established nonalcoholic fatty liver disease , suggesting that there are circumstances where the efficacy of detemir may be adversely affected by specific metabolic parameters .\npatient 1 was a 56yearold caucasian man with a 4year history of poorly controlled type 2 diabetes and marked hypertriglyceridemia ( random triglycerides were 28.7 mmol / l and total cholesterol was 7.9\nhis mother had type 2 diabetes , but there was no other family history of note .\nhe denied alcohol consumption for the previous 14 years and had been only a light drinker previously . at the time of starting insulin\nhe was being treated with metformin , gliclazide , fenofibrate , and omacor . on examination , he was obese with a body weight of 109 kg and bmi of 32 kg / m .\nglycated hemoglobin ( hba1c ) was 69 mmol / mol ( 8.5% ) , fasting triglycerides 8.4 mmol / l , and total cholesterol 4.5 mmol / l .\nmol / l ( egfr 102 ml / min/1.73 m ) and liver enzymes were slightly elevated : ast 71\nserum albumin was normal 47 g / dl ( 3550 ) , inr 1.04 , and hepatitis serology was negative .\nultrasound confirmed a 17.7cm spleen and ct demonstrated nonalcoholic fatty liver disease ( nafld ) . in view of splenomegaly\n, he underwent a bone marrow aspirate and trephine biopsy , both of which were normal .\na liver biopsy confirmed hepatosteatosis with marked steatosis , mild inflammatory activity , and hepatocellular ballooning ( fig .\n1a ) . in part of the biopsy , bridging fibrosis with parenchymal nodule formation was in keeping with cirrhotic transformation ( fig .\n( b ) reticulin stain ( gordon and sweet ) reveals , in part of the biopsy core , bridging fibrosis with parenchymal nodule formation in keeping with cirrhotic transformation .\ninsulin detemir ( 14 units nocte ) was commenced as his random glucose values were 1722 mmol / l .\nhe was using 158 units per day of detemir , in divided doses , plus insulin aspart 24 units with each meal . despite these doses ,\nmmol / l and hba1c remained unsatisfactory at 69 mmol / mol ( 8.5% ) .\nbasal insulin was then changed to insulatard 70 units per day in divided doses ( insulin aspart dose unchanged ) and within four months his hba1c had fallen to 51 mmol / mol ( 6.8% ) and by 12 months he had lost 6 kg of weight .\npatient 2 was a 68yearold man with a 20year history of type 2 diabetes and type v hyperlipidemia . for two years , after the diagnosis of diabetes , he was managed with oral hypoglycemic agents alone .\nhe then developed necrotizing pancreatitis ( considered secondary to hypertriglyceridemia ) and was treated with human isophane insulin and human soluble insulin for ten years before being switched to detemir and novorapid .\nhe was referred due to the patient 's concern of escalating insulin dose and associated weight gain of 20 kg over the previous five years . at the time of referral the detemir dose was 120 units twice daily and novorapid 120 units with each meal ( total of 600 units / day ) .\nhe did not drink alcohol . on examination he was obese with body weight of 126 kg and bmi of 44.6 kg / m .\nrandom triglycerides were markedly elevated ( 31.9 mmol / l ) , total cholesterol was 6.3 mmol / l , and hdl was 0.3\nthere was no clinical or biochemical evidence of any endocrinopathy to explain insulin resistance and no evidence of immunemediated insulin resistance .\nliver enzymes and synthetic function were normal but there was mild renal impairment ( serum creatinine 145 mol / l ; egfr 77ml / min/1.73 m ) .\ndetemir was changed to isophane insulin 100 units bd and novorapid reduced to 100 units / meal .\nafter six months , the dose of insulatard had stabilized at 140 units bd and novorapid 50 units tds ( 430 units / day 30% reduction in total daily dose ) , his weight remained unchanged and despite the reduction in insulin dose , hba1c improved to 50 mmol / mol ( 6.7% ) .\nthe two cases presented in this report showed that in patients with a history of severe hypertriglyceridemia and significant fat infiltration of the liver , a hepatoselective insulin ( detemir ) appeared less efficacious in achieving glycemic control .\ninsulin detemir differs from human insulin by the deletion of the amino acid threonine in position 30 of the b chain , plus the addition of a c14 fatty acid chain at position 29 of the b chain .\nthis allows detemir to reversibly bind to serum albumin 1 and is a characteristic that has led to it being considered a hepatoselective insulin : the albumin insulin molecule is unable to pass through the capillary endothelial cell barrier to reach peripheral adipocytes , whereas in the liver , the albumin detemir molecule is able to pass freely through the sinusoids .\nthis allows it to exert a greater effect on hepatocytes than in peripheral tissues 2 .\nhypothetically , the efficacy of hepatoselective insulin may be reduced in nafld by less hepatic exposure to insulin ( due to increased insulin clearance or to portosystemic shunting ) , or from direct hepatic parenchymal cell damage .\ngiven that the usual action of insulin is to stimulate the liver to store glucose in the form of glycogen and to switch off gluconeogenesis , underexposure of hepatocytes to insulin would lead to hyperglycemia .\na portosystemic shunt was thought to be unlikely in these patients as there were no radiological features of collateral ( variceal ) circulation .\nincreased clearance of detemir might have occurred ; premarketing studies suggested that hepatic impairment affected the bioavailability of insulin . in these studies\nthere was a 3547% faster clearance of detemir in patients with severe / moderate liver insufficiency as compared to healthy subjects 3 .\nby contrast , clearance of human insulin is usually reduced in liver failure 4 and insulin clamp studies with human insulin have shown decreased clearance in patients with fat infiltration of the liver 5 . in a mouse model of nafld ( induced by highfat feeding ) , there was decreased insulin activation of glycogen synthase and increased gluconeogenesis 6 during a euglycemic hyperinsulinemic clamp , suggesting a direct , adverse consequence of hepatic fat accumulation .\nthe closest model available is of detemir 's action in obesity where the presence of nafld may be inferred 7\n. a pharmacodynamic study of 18 subjects showed that in the presence of grade 1 obesity ( bmi 3035 kg / m ) a lower glucose infusion rate was required to maintain normoglycemia after administration of detemir , compared to neutral protamine hagedorn ( nph ) insulin or glargine 8 .\nadvanced hepatocellular fibrosis may be associated with a change in the configuration of the sinusoidal endothelium , including loss of fenestrations , which would reduce the exchanges between hepatocytes and sinusoidal blood .\ntherefore , this would suggest that in severe nafld / cirrhosis , higher doses of detemir insulin would be required .\nan alternative hypothesis is that hypertriglyceridemia may have a direct , adverse effect on detemir action .\nthe binding of detemir to albumin could be affected by the lipid content of plasma .\ncompetition experiments with fatty acids have shown that levemir can be displaced from human albumin by longchain fatty acids ( containing at least 12 carbon atoms ) but with much weaker competition by a medium chain fatty acid 9 .\nthe significance of this is uncertain , but potentially it could lead to loss of biological activity , or unpredictable release or clearance of levemir .\nantibody development has been observed in phase 3 clinical trials of detemir , but did not impact on metabolic control 10 .\nthere were no specific features of alternative cause(s ) for a relative lack of efficacy of insulin , such as lysosomal storage disease or monogenic insulin resistance syndromes and these were not tested for .\nit is possible that the cases described relate to less common etiologies of insulin resistance . in managing patients with diabetes , interindividual differences in response to insulin\nmay be encountered ; a relative lack of efficacy with one type of insulin may not be seen with an alternative insulin .\nsuch a response may be unrelated to the degree of hepatoselectivity of the insulin chosen . in conclusion\n, these two cases suggest that detemir may be less efficacious in patients with significant hypertriglyceridemia complicated by nafld .\nit is not possible to determine a precise mechanism to explain this observation but this could be due primarily to hypertriglyceridemia or due to the effects of infiltration of hepatic parenchyma with lipid .", "answer": "key clinical messageinsulin detemir is commonly used in obese patients with diabetes mellitus as it is considered hepatoselective and causes less weight gain . \n we describe a relative lack of effectiveness of detemir in patients with significant nafld and hypertriglyceridemia , compared to isophane insulin . \n this may affect how such patients are managed with insulin .", "id": 308} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe clinical effects of toxic alcohols are mainly due to depression of both the central nervous system and myocardial function.1 there are very few published reports of the magnetic resonance imaging ( mri ) features of central nervous system involvement in various types of toxic alcohol poisoning.15 all reports mention cerebral and/or cerebellar toxicity , also known as toxic encephalopathy . there have been no published reports of brain and spinal cord injury secondary to isopropanol ( isopropyl alcohol ) intoxication.15\na 60-year - old caucasian merchant ship captain presented to the emergency department of our hospital with headache , dizziness , and disorientation one day after ingestion of isopropanol along with ethanol ( ethyl alcohol , drinking alcohol ) .\nhe had celebrated his 60th birthday aboard ship by consuming ethanol and then isopropanol , because ethanol was not available later .\nhis colleague accompanying him to the hospital brought an empty bottle of rubbing alcohol labelled as 70% volume per volume isopropyl alcohol with a capacity of 473 ml ( one pint ) .\nthe label on the bottle mentioned its indication for use as a first aid antiseptic and for rubbing and massaging .\nthe patient s colleague mentioned that the patient had consumed most of the liquid in the bottle and that he ( the colleague ) had consumed a small amount .\nthe patient s colleague did not give any recent or past history of substance abuse .\nan unenhanced computed tomography ( ct ) scan of the brain was performed immediately and was unremarkable .\nthe patient collapsed in the hospital just 30 minutes after the ct scan was done .\nhe became deeply comatose with a score of 3/15 on the glasgow coma scale ( a scale to assess central nervous system status where a total score of 15 indicates best and normal outcome ) .\nhe also developed hypotension , with a blood pressure of 80/40 mmhg , a pulse rate of 65 per minute , and a respiratory rate of 8 per minute .\nafter administration of intravenous fluids and endotracheal intubation , the patient was admitted to the intensive care department .\nblood investigations revealed leukocytosis of 26,000 ( normal 4,00010,000 ) white blood cells per l , a hemoglobin of 15.7 ( normal 1317 ) g / dl , and a mean corpuscular volume of 93 ( normal 83101 ) fl . the initial arterial blood gas report indicated a ph of 6.731 ( normal 7.357.45 ) , a pco2 level of 28.2 ( normal 3548 ) mmhg , a po2 level of 141 ( normal 83108 ) mmhg , a bicarbonate level of 3.5 ( normal 2128 ) mmol / l , and oxygen saturation of 95% ( normal 95%98% ) .\nother blood investigations revealed a blood urea nitrogen of 9.5 ( normal 1.78.3 ) mmol / l , serum creatinine of 157 ( normal 62124 ) mol / l , na of 141 ( normal 134146 )\nmmol / l , cl of 107 ( normal 96110 ) mmol / l , hco3 of 5 ( normal 2430 ) mmol / l , and capillary blood glucose of 7.2 ( normal 3.35.5 ) mmol / l .\nhis blood lactic acid level was significantly elevated at 8.7 ( normal 0.52.2 ) mmol / ml .\nblood levels of isopropanol and other toxic alcohols ( like methanol , ethylene glycol , propylene glycol , and diethylene glycol ) could not be obtained because the necessary investigations were not available .\ninvestigations repeated at 2-hour intervals revealed increasing renal impairment , hyperglycemia , and electrolyte imbalance ( low bicarbonate levels and hyperkalemia ) .\nno growth was detected on cultures of urine and blood , and no crystals were found in the urine on microscopic examination .\nthe patient received hemodialysis because of severe acidosis and hyperkalemia , which led to gradual improvement in his blood ph and lactic acid levels .\nhe was also treated with norepinephrine ( as a vasopressor ) and intravenous fluids , but there was no improvement in blood pressure .\nhe received 500 ml of fractionated plasma protein stat over 30 minutes , 2,000 ml of normal saline over 2 hours , and was then kept on 200 ml / hour of normal saline .\nhe did not respond to intravenous fluids and within the first 2 hours was started on norepinephrine 10 g per minute , which was gradually increased up to a maximum dose of 90 g per minute .\nunenhanced mri scans of the brain and spine performed 6 days after hospital admission showed bilaterally symmetrical hyperintensities on t2-weighted , t1-weighted , t2 * -weighted , fluid attenuated inversion recovery ( flair ) , and diffusion - weighted images in the cerebral and cerebellar cortex and white matter , basal ganglia , thalami , and brainstem ( figures 14 ) . a swollen and edematous cervical spinal cord was noted with t2-weighted and flair hyperintensities within it ( figures 2 and 4 ) .\ncerebellar tonsillar herniation of 17 mm was noted to be compressing the proximal cervical cord ( figures 2 and 4 ) .\npetechial hemorrhages were noted in the brainstem and the gangliocapsular regions bilaterally ( figure 1 ) .\nall the features described above are compatible with toxic brain and cervical spinal cord damage .\nfinally , the patient expired ten days after hospital admission , despite his improving blood picture .\nchemicals involved in alcohol intoxication are ethanol , methanol , isopropanol , ethylene glycol , diethylene glycol , and propylene glycol .\nethanol is considered as a drinking alcohol and the rest as toxic alcohols . among the toxic alcohols ,\nisopropanol itself is more toxic than its metabolite ( acetone ) , while the metabolites of the rest of the toxic alcohols are more toxic than the parent alcohol .\nisopropanol poisoning is characterized by an increased osmolal gap in the setting of positive serum and urine ketones and does not cause metabolic acidosis , while the rest of the toxic alcohols cause mild to severe metabolic acidosis.1 when not mixed with ethanol or other intoxicants , the signs and symptoms of intoxication may start earlier ( few hours ) after isopropanol ingestion and may be delayed by up to a day or more after ingestion of other toxic alcohols . unlike methanol and ethylene glycol ,\nisopropanol is more toxic than its metabolites ; hence , alcohol dehydrogenase inhibitors are not given.1 hemodialysis removes both isopropanol and its metabolite.1 in our case , the clinical and biochemical features were atypical for isopropanol toxicity likely due to coconsumption of ethanol and delayed patient presentation .\ningestion of approximately 200 ml of pure isopropanol can be lethal.1 the patient was managed symptomatically , mainly with hemodialysis .\nwe wish to emphasize the atypical mri features in this case that have not been reported before in cases of toxic alcohol ingestion . in our case ,\nthese were likely due to reduced brain perfusion.6 these lesions were bilaterally symmetrical , and the distribution of the affected areas was highly indicative of a toxic injury.6 bilateral involvement of the basal ganglia and thalami has been reported in a few cases of ethylene glycol intoxication . however , cervical spinal cord involvement and cerebellar tonsillar herniation has not been reported before in cases of toxic alcohol ingestion and even in cases of other substance abuse . in humans ,\nthe opioid receptors are predominantly present in the cerebellum and the limbic systems , thus causing cerebellar - predominant toxicity in cases of opioid intoxication.6 involvement of the basal ganglia is also noticed in a few of these cases.6 a similar explanation may be given in cases of alcohol intoxication . to the best of our knowledge ,\nthis is the first reported case of cerebral , cerebellar , brainstem , and cervical spinal cord involvement on mri secondary to isopropanol intoxication .\nhere we present a very rare case of involvement of cerebrum , cerebellum , brainstem , and cervical spinal cord demonstrated on mri after coconsumption of isopropanol and ethanol . to our knowledge ,\ninvolvement of the cervical spinal cord and cerebellar tonsillar herniation after toxic alcohol ingestion have not been reported before in the published literature .", "answer": "a 60-year - old man presented with headache , dizziness , and disorientation one day after consumption of isopropanol along with ethanol . computed tomography ( ct ) of the brain performed immediately was unremarkable . \n the patient collapsed within the hospital 30 minutes after the ct scan was done , and remained comatose until death , showing no improvement with symptomatic treatment . \n magnetic resonance imaging of the brain and spine done 6 days after admission revealed bilaterally symmetrical hyperintensities involving the cerebral and cerebellar cortex and white matter , basal ganglia , thalami , and brainstem on t2-weighted , fluid attenuated inversion recovery and diffusion weighted images ; similar hyperintensities were seen involving the swollen and edematous cervical spinal cord and cerebellar tonsillar herniation compressing the proximal cervical cord . \n petechial hemorrhages were also noted within the brainstem . \n these features are compatible with toxic injury to the brain and cervical spinal cord . to our knowledge , \n the magnetic resonance imaging features of brain and spinal cord injury and cerebellar tonsillar herniation , secondary to isopropanol intoxication have not been reported in the published literature before .", "id": 309} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndilatation of various lengths and severity of the common bile duct ( cbd ) , entitled choledochal cyst , has been detected in utero and usually presents with icterus in infancy , clinically mimicking biliary atresia and neonatal hepatitis1 ) .\nyounger children and occasionally infants tend to present with painless jaundice , and older children present with recurrent abdominal pain , which was actually due to acute pancreatitis12 ) .\npostnatally , ultrasonography ( us ) is the initial diagnostic modality of choice , allowing for precise measurements of intra- or extrahepatic duct dilatation and identification of stones and sludge .\nmagnetic resonance cholangiopancreatography ( mrcp ) and endoscopic retrograde cholangiopancreatography ( ercp ) has superseded the use of computed tomography ( ct ) for preoperative anatomical delineation of the pancreaticobiliary tract .\nhere we present the biggest choledochal cyst reported in infancy in the literature to our knowledge .\na term female baby was born by normal delivery route after consanguineous marriage , at house , in syria as the 6th child of her parents .\nthis family was living the civil war in syria at that time . during 4 months period abdominal distension had increased . because of restlessness and growing abdominal distension\nbut as a result of investigations they were sent home because of normal laboratory results . after 15 days they admitted to hospital because of jaundice and abdominal cyst\nshe had referred to our hospital ( in turkey ) with the preliminary diagnosis of abdomianl cyst and hepatitis developed due to compression of cyst . on her admission ,\nus revealed giant abdominal cyst with thin wall and liquid - debris level extending from right upper quadrant to pelvic region .\nit was suspected that bile duct 's dilatation was due to abdominal giant cyst 's pressure .\nshe was operated with the differential diagnosis of duplication , omental or mesenteric cyst . at operation , a giant type 1a choledochal cyst , 160 mm in diameter , was surprisingly detected ( fig .\nserum levels of bilirubin decreased sharply and the patient was discharged without any problems on the tenth postoperative day .\na choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts2 ) .\ntype ia is a cystic dilation of the cbd ; type ib is a focal segmental dilation of the distal cbd ; type ic is a fusiform dilation of both the common hepatic duct and cbd . in type ii , the cyst forms a diverticulum from the extrahepatic bile duct .\ntype iii , also known as choledochocele , is a dilation of the distal cbd lying mainly within the duodenal wall .\ntype iv is essentially type i anatomy with either intrahepatic bile duct cyst ( iva ) or choledochocele ( ivb ) .\nsome authors refer to caroli 's disease with multiple cystic dilations of the intrahepatic biliary tree as type v23 ) . in our case\nthere was a cystic dilation of the cbd as a type ia choledochal cyst with minimal dilatation of intrahepatic bile ducts .\nthis malformation primarily affects girls ( 4:1 ) and about 80% become symptomatic during childhood .\ncholedochal cysts remain relatively uncommon in western europe and the united states , although they are appreciably more common in asia .\nobstructive jaundice is the main presentation symptom in children , but abdominal pain is the commonest symptom in adults .\nthe classical triad of pain , jaundice and a palpable mass is uncommon , occurring in no more than 6% in one uk series4 ) .\nthe complications of congenital cystic dilatation of the bile duct are biliary stone formation , progressive biliary cirrhosis with portal hypertension , and carcinoma .\nfusiform lesions are never large enough to be palpable while multiple intrahepatic type 4 lesions cause predisposition to stone formation and sepsis .\na wide variety of imaging techniques are available which noninvasively reconstruct biliary anatomy and give an excellent idea of biliary function .\nalthough us is the first described imaging method to determine the cbd cyst , ct , mrcp , and ercp are superior to assess the extention of the cyst and associated pathologies such as cholangitis , pancreatitis and pancreaticobiliary junction anomaly . in our case , we used us and ct to identify the abdominal mass ' origin . because of the diameter of the cyst , cbd cyst was not thought in the differential diagnosis .\ncbd malformations should be kept in mind as a differential diagnosis of the cystic mass regardless of size , and patient 's age .\nsurgery is the main choice of treatment but some centres in south american and asia have reported ercp and sphincterotomy alone as definitive treatment for mild fusiform dilatation although their long - term prognosis is not known3 ) . at operation , it was difficult to make the differential diagnosis of our giant cyst .\nit was important to make the dissection of the cyst carefully in order to avoid the iatrogenic injury .\nfollowing the diagnosis of choledochal cyst was confirmed , hepaticojejunostomy was easier depending on the wide common hepatic duct of our huge cyst .\ntang et al.5 ) reported a study that involves 62 children ( average age of 2.3 years ) who had cysts with the average diameter of 42 mm ( range , 12158 mm ) .\nthere is no information about the child'a age with the 158-mm cyst . as our knowledge we report the biggest choledocal cyst case in infancy in the literature . in conclusion ,\ncbd malformations should be kept in mind as a differential diagnosis at the cystic mass regardless of cyst 's size , and patient 's age , especially in children presented with abdominal pain , jaundice , and palpable mass .", "answer": "choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts . \n postnatally , ultrasonography is the initial diagnostic modality of choice , allowing for precise measurements of intra- or extrahepatic duct dilatation and identification of stones and sludge . \n symptoms depend on the age at presentation . \n common bile duct malformations should be considered as a differential diagnosis of a cystic mass regardless of the cyst 's size or patient 's age , especially in children presenting with abdominal pain , jaundice , and palpable mass . to the best of our knowledge , \n we report the largest choledochal cyst in infancy .", "id": 310} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nas a national reference center for q fever , our center receives samples from france and other regions for serologic , molecular , histologic , and immunohistochemical analyses as described ( 57 ) .\nin 2012 , we received a cardiac valve sample from a patient in cayenne with q fever endocarditis who had undergone surgery in martinique . in the same year , we collected 4 heparinized blood samples from patients with acute q fever from cayenne that were collected before initiation of antimicrobial drug treatment .\nserologic titers of igg1 increased to 51,200 in this patient , and results of quantitative pcr ( qpcr ) and immunohistochemical analyses of the valvular sample were positive for c. burnetii ( figure 1 ) .\nthe other 4 patients ( 2 men and 2 women ) had fever and acute pneumonia , and 2 of them also had increased transaminase levels .\nthe heparinized blood samples were tested by using a specific qpcr ; samples from only 1 patient were positive for c. burnetii .\nimmunohistochemical detection of coxiella burnetii in resected cardiac valve of a 60-year - old man with q fever endocarditis , cayenne , french guiana .\nwe successfully cultured c. burnetii from the valvular sample after incubation for 16 days and from 3 blood samples after incubation for 25 , 32 , and 32 days .\nparadoxically , the only blood sample that was positive by qpcr was negative by culture .\nspacers cox 51 and cox 20 were the most discriminating spacers in identifying this genotype , and the 3 isolates from the blood cultures were also identified by these 2 spacers as genotype 17 ( figure 2 ) .\nthis genotype had been identified in our laboratory only once , in 2000 in an aortic valve of a 40-year - old french man who had undergone surgery in france , had q fever endocarditis , and was co - infected with streptococcus oralis .\nretrospectively , we found that patient had lived in cayenne for years before his diagnosis with q fever endocarditis .\ntherefore , all genotype 17 isolates were obtained from who lived or had lived in cayenne , making it unique to this area .\nwe determined the antimicrobial drug susceptibilities of these isolates , and the mic of doxycycline was 0.25 g / ml for all isolates ( 10 ) .\nphylogenetic diversity of 34 genotypes of coxiella burnetii identified by using multispacer sequence typing ( mst ) .\nscale bar indicates nucleotide substitutions per site . for the past 10 years , routine cell culture for c. burnetii has been performed in our laboratory .\nwe found that the proportion of isolates obtained from blood samples of patients with acute q fever was higher for patients from cayenne than for patients from metropolitan france .\nwe obtained 3 isolates from 5 blood samples from untreated patients in cayenne and 3 isolates from 65 samples from patients in metropolitan france ( p = 0.003 , by fisher exact test ) .\nhowever , we did not find any difference with respect to the culture delay between patients from the 2 locations .\nour work shows that genotype 17 , a unique genotype , is circulating in cayenne .\nthis genotype is related to genotypes that harbor the qph1 plasmid , which causes the most severe clinical forms of acute q fever in experimental animal models ( 11,12 ) .\nonly bacteria from this group and bacteria containing the qpdv plasmid have been found in cases of human acute q fever ( 9,13 ) .\nwe believe that severity of q fever infection is related to the strain of c. burnetii circulating in cayenne . because the population in french guiana is a large diversity of creole , amerindian , maroon , caucasian , and asian persons ( 14 ) , we excluded the hypothesis that genetic susceptibility of patients from cayenne to c. burnetii infection might be related to severity of the disease .\nwe observed a higher rate of strain isolation from the blood of patients from cayenne than from the blood of patients from metropolitan france .\nthis difference may be related to a higher bacterial load in blood or a greater ability of the bacteria to grow on cell cultures .\nthis second hypothesis seems more likely because even if the observed delay for the first culture was the same for genotype 17 and other genotypes , the strain from cayenne was isolated more frequently in the cell line that we used ( hel cells ) than other strains of c. burnetii from france . in addition , we did not find a higher number of dna copies in the blood of patients from cayenne , and qpcr results were not correlated with culture results . c. burnetii isolates from cayenne were susceptible to antimicrobial drugs , particularly doxycycline .\nthese isolates cause acute pneumonia and endocarditis . among the 34 genotypes identified in our study by multispacer\na larger biodiversity of strains has been observed in samples from patients in metropolitan france ( 9 ) , where 21 genotypes circulate ( figure 2 ) .\nin contrast , during the recent q fever outbreak in the netherlands , it appears that a single strain ( genotype 33 ) was responsible for the epidemic ( 15 ) .\nwe believe that there has been an epidemic developing in cayenne since 1996 that is caused primarily , if not solely , by a single strain that has circulated since at least 2000 , whose reservoir is unknown ( 1,2 ) . in conclusion ,\nc. burnetii genotype 17 is circulating in french guiana and causing acute infections and endocarditis .\nthis strain is epidemic and most likely causes more acute infections with exacerbated immune responses than other known genotypes of c. burnetii .", "answer": "acute q fever is an emergent and severe disease in french guiana . \n we obtained 5 coxiella burnetii isolates from samples of patients from cayenne and found an epidemic clone circulating in cayenne . \n this clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains .", "id": 311} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin some clinical situations , such as root canal overinstrumentation , apical resorption and teeth with open apices , there may be extrusion of the filling material , either gutta - percha , root canal sealer or both , due to the difficulty or impossibility to lock the master gutta - percha cone . in these situations ,\nfabrication of an apical plug with calcium hydroxide and , more recently , with mineral trioxide aggregate ( mta ) has been suggested2,4,13,21,25,26 .\nmta was introduced in the early 1990 's as an experimental material developed by dr .\nmahmoud torabinejad at loma linda university , usa . this material was originally indicated as a retrograde filling material for use in endodontic surgery and cases of intraradicular and furcal perforations18 . since then\n, it has been used in different clinical situations , such as communicating internal and external resorptions , as capping material in mechanically exposed pulps , as intracoronal barrier during internal bleaching of endodontically treated teeth , and as apical plug in case of difficulty to lock the master gutta - percha cone4 .\nthese indications of mta are related to the possibility of use in moist environments , as in most aforementioned indications , and mainly to its biocompatibility4,26 .\nthe sealing ability of mta apical plug and its thickness have been investigated by several authors2,13,16,17,20,21,26 .\nfour - millimeter - thick plugs have been shown to be the most efficient with respect to root canal sealing ability and resistance to displacement13,20,21,26 .\nall of these studies have sought an alternative to mta apical plug as well as its most appropriate thickness .\nwucherpfennig and green27 ( 1999 ) have called the attention to the fact that mta and portland cement were similar materials .\nother studies were conducted and confirmed this similarity by means of microbiological , chemical , physical and biological behavior tests1,5,8,10,11,15,23 .\nthe purpose of this study was to evaluate the sealing ability of apical plugs made of white and gray mta - angelus ( angelus solues em odontologia , londrina , pr , brazil ) and white portland cement ( votorantim cimentos , votorantim , so paulo , sp , brazil ) placed via the root canal and having different thicknesses ( 2 , 5 and 7 mm ) .\nthis study was approved by the institutional review board of the dental school of bauru , university of so paulo , brazil .\nninety extracted human single - rooted teeth with intact roots and completely formed apices were used .\nthe teeth were obtained from the files of the department of endodontics of the dental school of bauru and were kept in 10 % aqueous formalin solution .\nthe dental crowns were sectioned at the cementoenamel junction with a low - speed diamond saw ( kg sorensen , so paulo , sp , brazil ) under continuous water spray to obtain access to the root canal .\nthe root canal length was determined by inserting a size 15 k - file ( dentsply - maillefer instruments sa , ballaigues , switzerland ) into the canal until its tip reached the apical foramen . the working length was established by subtracting 1 mm from this measurement .\nthe stepback technique was employed and the root canal was flared using a size 60 k - file to the working length .\ninstrumentation was aided by irrigation with 1 ml of 1% sodium hypochlorite solution ( biodinmica qumica e farmacutica ltda , ibipor , pr , brazil ) alternated with the sequence of instruments , followed by a final flushing with 1 ml of sterile water .\nthe teeth were assigned to 3 groups ( n=30 ) , according to the material used for fabrication of the apical plugs : group a = placement of gray mta - angelus plugs ; group b = placement of white mta - angelus plugs ; group c = placement of white portland cement plugs .\nthe groups were further subdivided into groups of 10 teeth each , according to the thickness of the apical plugs , namely 2 , 5 and 7 mm ( table 1 ) . before standardization of the foraminal opening\n, the roots were made impermeable by application of a layer of epoxy adhesive ( araldite - ciba - geigy s.a .\n, taboo da serra , sp , brazil ) , followed by two coats of nail polish ( cosbra cosmeticos ltda . , so paulo , sp , brazil ) .\nthe foramen diameter was standardized by inserting the 40 k - file 1 mm beyond the apical foramen , so that only the apical opening would not be impermeable . for fabrication of the apical plugs ,\nthe tested materials were applied with a size 4 lentulo spiral ( dentsply - maillefer instruments sa , ballaigues , switzerland ) at the apical end of the root , trying to fill it completely .\nthe material was condensed with the tip of a size 40 k - file involved in cotton for achievement of the plug19 .\nnext , using a size 40 k - file with a rubber stop positioned 2 , 5 and 7 mm shorter than the root canal length , the excess material was removed for fabrication of 2- , 5- and 7-mm - thick apical plugs , respectively .\nfinally , the root canal walls were cleaned with the tip of an instrument wrapped in moist cotton .\nthen , the canal entrances were sealed with epoxy adhesive and nail polish , and the roots were immersed in 0.2 % rhodamine b solution ( labsynth produtos para laboratrios ltda , diadema , sp , brazil ) at ph 7.0 for 72 hours at 37c . after this period , the roots were removed from the dye , washed in running water for 24 hours , had the impermeable coating scraped away and were washed for additional 12 hours .\nthe roots were then sectioned longitudinally in a buccolingual direction for exposure of the apical plugs , photographed with a digital camera ( canon eos rebel 300 d ) and analyzed by image tool software ( university of texas health science center , san antonio , tx , usa ) .\n\n table 2 shows the percent marginal leakage for the different materials for each plug thickness .\ntables 3 , 4 and 5 show the results of the kruskal - wallis statistical test for comparison among groups a ( mta - angelus gray ) , b ( mta - angelus white ) and c ( white portland cement ) with respect to the plug thicknesses ( 2 , 5 and 7 mm ) . a statistically significant difference ( p<0.05 )\nwas observed between groups a and b as to the leakage in 2- mm - thick plugs , with better results for group a ( table 3 ) .\nmaterials did not show statistically significant difference ( p>0.05 ) when groups with 5-mm - thick plugs were compared to each other ( table 4 ) . regarding the 7-mm - thick plugs , there was statistically significant difference ( p<0.05 ) between groups a and b and between groups b and c , with worst results for group b in both comparisons ( table 5 )\n. in figure 1 shows the graphic presentation of percent marginal leakage ( 0.2% rhodamine b ) in the root canals , regarding the tested materials and plug thicknesses .\nit is possible to verify that 2-mm - thick plugs yielded the least satisfactory results in all groups , whereas the 7-mm - thick plugs yielded the best results for groups a and c , yet not for group b , in which the 5-mm - plugs had the best results as to dye leakage .\nthis study investigated the sealing ability of gray mta , white mta and white portland cement used for fabrication of apical plugs , given that this procedure is often required in the clinical practice12,14,19 , mainly in cases where appropriate adaptation of the master gutta - percha cone is difficult .\ntorabinejad and chivian25 ( 1999 ) pointed out that the goal of an apical plug is to induce hard tissue formation , in order to prevent filling material extrusion in teeth with open apices .\nthe use of methylene blue in marginal sealing studies has been questioned , due to its incompatibility with alkaline substances , which may induce discoloration of the dye .\nwhen calcium oxide is mixed with water , it results in the formation of calcium hydroxide , with a subsequent increase in ph , as previously demonstrated by duarte , et al.9 ( 2003 ) .\ntherefore , rhodamine b dye solution is more appropriate for evaluating the sealing ability of mta22,24 . in the present study , 5- and 7-mm - thick plugs\nwere more efficient for apical sealing than 2-mm - thick plugs , regardless of the material utilized ( table 1 and figure 1 ) , which is in agreement with the findings of previous2,13,21,26 . in group\nb ( white mta ) , the 5-mm - thick plugs had better performance than the 2- and 7-mm - thick plugs , yet without statistically significant difference .\nwith regard to tested materials , no statistical difference was expected among them because the chemical components of mta and portland cement are the same , except for bismuth oxide , which provides radiopacity to mta8,10,11 .\ncamilleri , et al.7 ( 2005 ) evaluated the chemical constitution and biocompatibility of white and gray portland cement , white and gray mta , portland cement clinker without calcium sulfate and portland cement clinker without calcium sulfate with addition of bismuth oxide .\nthey concluded that the chemical composition of the tested materials is similar , primarily containing tricalcium silicate and dicalcium silicate .\nthe white cements differ from the gray cements by the small quantity of iron oxide ( feo ) , while mta differs from portland cement due to the presence of bismuth oxide .\nthere was no difference between white and gray mta , and the addition of bismuth oxide did not interfere with the biocompatibility of cements . in the present study , white mta showed poorer results than gray mta and white portland cement for all tested plug thicknesses ( table 1 ) .\nasgary , et al.3 ( 2005 ) observed significant differences between gray and white mta , especially in the contents of aluminum trioxide ( al2o3 ) , magnesium oxide ( mgo ) and iron oxide ( feo ) .\nhowever , these differences are not enough to explain the results of the present study , in which gray mta showed better results than white mta as to dye leakage .\nmatt , et al.21 ( 2004 ) observed similar results in their study , where apical plugs made with gray mta were more efficient than those made with white mta .\nas to the fabrication of apical plugs , torabinejad and chivian25 ( 1999 ) recommended carrying the mta with a large amalgam carrier to the root canal and then condensing the material to the apical end of the root with pluggers or paper points .\nsometimes , this procedure is difficult due to the root canal diameter and anatomy . in the present study ,\nmta and portland cement were carried to the root canal with a size 4 lentulo spiral , according to the technique proposed by bramante , et al.6 ( 2004 ) .\nthe lentulo spiral is used to carry the mta in paste consistence more easily to the root canal end in a fast and correct manner .\nanother important factor is material condensation at the end of the root canal because the apical plug should resist the filling material .\nthis condensation is more effective when performed with a k - file compatible with the root canal diameter and with the tip wrapped in a cotton mesh .\ncleaning of the root canal walls and removal of excess material must be performed with the same k - file wrapped in moist cotton in sterile saline , not to interfere with the proper root canal filling .\nthe findings of the present study showed that gray mta and portland cement had better sealing ability than white mta when used as apical plugs .\ndye leakage was smaller for 5- and 7-mm - thick plugs compared to 2-mm - thick plugs .", "answer": "this study evaluated the sealing ability of apical plugs made of white and gray mta - angelus and white portland cement placed via the root canal and having different thicknesses ( 2 , 5 and 7 mm ) . \n ninety extracted human single - rooted teeth were instrumented using a size 40 k - file to standardize the foraminal opening by the stepback technique . \n the teeth were assigned to 3 groups ( n=30 ) , according to the material used for fabrication of the apical plugs : a = gray mta ; b = white mta ; c = white portland cement . \n the groups were subdivided into groups of 10 teeth each according to the apical plug thickness ( 2 , 5 and 7 mm ) . \n marginal apical dye leakage was assessed using 0.2% rhodamine b solution in which the specimens were immersed for 72 hours at 37c . \n the roots were sectioned longitudinally in a buccolingual direction for apical plug exposure , and digital photographs were taken and analyzed by image tool image - analysis software . \n data were analyzed statistically by kruskal - wallis and dunn 's tests . \n significance level was set at 5% . \n the least percent leakage was observed for 5- and 7-mm - thick plugs ( p<0.05 ) . \n no significant difference ( p>0.05 ) was found between gray mta and white portland cement . among the three materials analyzed , white mta presented the highest marginal leakage ( p<0.05 ) . \n the findings of the present study showed that gray mta and portland cement had better sealing ability than white mta when used as apical plugs . \n dye leakage was smaller for 5- and 7-mm - thick plugs compared to 2-mm - thick plugs .", "id": 312} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nits prevalence varies among ethnic groups , but it affects approximately 13% of the population in industrialised countries .\nits clinical course can vary greatly in terms of morphology , distribution , and severity of the disease . in its commonest subtype\nit is characterised by the formation of discrete , pink , scaly plaques occurring at various sites on the body .\nalthough it can present at any age , it occurs most frequently between the ages of 15 and 20 and again between 50 and 60 years of age .\npsoriasis has very significant psychosocial morbidity which appears independent of objective disease severity [ 3 , 4 ] .\nit is also associated with an increased risk of cardiovascular disease and mortality [ 58 ] . indeed patients with psoriasis have almost twice the risk of cardiovascular disease when compared with normal controls [ 9 , 10 ] .\na number of studies have shown significantly increased rates of hypertension , dyslipidemia , diabetes mellitus , smoking , and excessive alcohol consumption in patients with psoriasis .\nfound that patients with severe psoriasis had an increased risk of diabetes ( odds ratio ( or ) , 1.62 ; 95% confidence interval ( ci ) , 1.32.01 ) , obesity ( or , 1.79 ; 95% ci , 1.552.05 ) , and smoking ( or , 1.31 ; 95% ci , 1.171.47 ) compared with controls .\nprodanovich et al . also found a higher prevalence of these risk factors in patients with psoriasis .\nhowever , even after controlling for these variables , they found a higher prevalence of ischemic heart disease ( or 1.78 ; 95% ci , 1.512.11 ) , cerebrovascular disease ( or , 1.70 ; 95% ci , 1.332.17 ) , and peripheral vascular disease ( or , 1.98 ; 95% ci , 1.322.82 ) when compared with controls .\nindeed they also found psoriasis to be an independent risk factor for mortality ( or , 1.86 ; 95% ci , 1.562.21 ) as a result of the association with atherosclerosis . \nthese risk factors in combination with the chronic inflammatory process are thought to be significant components in the development of vascular disease [ 9 , 14 ] .\nlinks with alterations in levels of folate and homocysteine in patients with psoriasis have also been implicated in contributing to the propagation of atherosclerosis and atherothrombotic events [ 9 , 15 , 16 ] .\n recent case control studies have demonstrated that patients with psoriasis have lower levels of folate in comparison to normal controls [ 9 , 15 , 17 , 18 ] .\npostulated mechanisms include alterations in gut absorption of folate due to microscopic inflammatory changes seen in the bowel mucosa of patients with active psoriasis and psoriatic arthritis .\na more likely explanation however probably relates to the accelerated keratinocyte turnover seen in patients with psoriasis .\nthis action results in excessive consumption of folate used to methylate dna in these actively dividing cells thus lowering folate levels . conversely homocysteine levels are elevated in psoriasis patients [ 9 , 15 , 17 ] . in one case - controlled study this was found to directly correlate with disease severity and to be inversely related to plasma folate levels .\nplasma homocysteine is an independent risk factor for cardiovascular disease [ 19 , 20 ] , peripheral vascular disease , cerebrovascular disease and possibly alzheimer 's diseases .\nthe magnitude of this risk is equivalent to the risk of smoking or dyslipidemia . \numol / l ) is thought to favour atherosclerosis and vascular thrombosis by a number of mechanisms .\nthese include damaging endothelial cells , promoting clot formation , decreasing flexibility of blood vessels leading to aortic stiffness , and reducing blood flow velocity .\nthe endothelial dysfunction is thought to result from the accumulation of asymmetrical dimethylarginine ( adma ) which is a natural inhibitor of nitric oxide synthase . as a result\nthere is a reduction in the production of the vasodilator nitric oxide which protects the vessel wall against the pathogenesis of atherosclerosis and thrombosis ( figure 1 ) .\nit has been suggested that hyperhomocysteinemia in addition to other factors may be caused by reduced levels of folate in these patients [ 9 , 15 ] .\ncoenzymes methylene tetra - hydrofolate , methylcobalamin , and pyridoxal phosphate are essential for three of the enzymes involved in the metabolism of homocysteine and are dependent on folate , vitamin b12 and b6 , respectively . hence in patients with severe psoriasis who have large areas of rapid skin turnover and increased keratinocyte activity\nthis in turn results in reduced breakdown and elevated serum levels of homocysteine with all of its adverse effects .\n it appears from this paper that patients with psoriasis have lower levels of folate and higher levels of homocysteine than normal controls . as psoriasis\nis associated with an increased risk of cardiovascular morbidity and mortality and homocysteine is an independent risk factor for cardiovascular disease , it may seem intuitive that managing this risk factor would have beneficial effects in terms of cardiovascular mortality and morbidity . \nfolate has long been used in combination with methotrexate in the management of psoriasis , psoriatic arthritis , and rheumatoid arthritis . here\nit is effective in reducing gastrointestinal side effects and liver function test abnormalities . in a retrospective cohort study looking at over seven thousand patients with psoriasis , methotrexate\nwas found to reduce the incidence of vascular disease and this reduction was further enhanced when folic acid was added ( figure 2 ) .\nhowever , homocysteine levels can be elevated for other reasons including obesity , hypertension , smoking , and excessive alcohol consumption all of which have significant prevalence in the psoriatic patient population .\narmitage et al . in a double - blinded randomised control trial assessed the beneficial effects of lowering homocysteine levels in over 12,000 post - mi patients .\nthey failed to demonstrate any benefit in vascular outcomes from long - term reductions in homocysteine with folate and vitamin b12 supplementation .\nit is possible that hyperhomocysteinemia in psoriasis is independent of folate deficiency and instead is linked with other risk factors such as hypertension and obesity .\n the psoriatic march , a concept of how severe psoriasis may drive cardiovascular morbidity , suggests a process of genetic susceptibility triggered by environmental factors and immune responses .\nit is this chronic inflammatory burden and state of insulin resistance which can result in endothelial dysfunction and ultimately atherosclerosis .\n it is well established that folic acid supplementation has a role in the treatment of psoriasis in conjunction with methotrexate treatment .\nhowever , the evidence to support its use in reducing the risk of cardiovascular disease by directly impacting on plasma homocysteine levels is lacking .\nnow management of associated risk factors such as obesity , dyslipidemia , and hypertension as well as encouraging smoking cessation are paramount for these patients as is , of course , the management of their skin .", "answer": "psoriasis is a chronic inflammatory skin condition with an increased risk of cardiovascular disease . \n this risk has been attributed to an association with many independent risk factors including obesity , hypertension , smoking , and dyslipidemia . \n psoriasis patients also have lower levels of folate and conversely higher levels of homocysteine , which in itself is a risk factor for cardiovascular disease . \n it has been postulated that low folate levels in this group may be a direct cause of hyperhomocysteinemia and therefore a treatable risk factor by folate supplementation . this paper looks at the literature published to date on the relationship between psoriasis , homocysteine , and folate levels .", "id": 313} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsalivary gland neoplasms constitute an important area in the field of pathology of head and neck region .\nthey are mainly classified as either hodgkin 's or non - hodgkin 's lymphoma ( nhl ) .\nnhl comprises a heterogeneous group of lymphoid neoplasms with a spectrum of behaviour ranging from relatively indolent to highly aggressive and potentially fatal .\nthe vast majority of nhl represent b cell and less commonly t cell lineage neoplasm .\nnhls of b cell origin are known to be relatively common in extra nodal sites and many are thought to originate from mucosa associated lymphoid tissue ( malt ) .\nthis is a low to intermediate grade lymphoma that show a follicular architecture and represents the neoplastic counterpart of germinal center b lymphocytes .\nfollicular lymphoma is very uncommon under the age - group of 40 years and is extremely rare in children .\nthe t ( 14;18 ) ( q32;q21 ) chromosome translocation has been purported to be the cytogenetic hallmark of follicular lymphoma .\nthe molecular consequence is deregulation of bcl2 expression leading to over expression of bcl2 proteins in neoplastic follicles .\na 40-year - old female patient reported to our institute with a complaint of swelling in the left side of lower jaw since 2 months [ figure 1 ] .\npost its onset , the swelling gradually increased in size over a period of 2 months .\nthe patient is a known diabetic since 5 years and is under oral anti diabetic medication .\nconcurrent with the history of swelling , the patient gives a history of weight loss in past 2 months .\nno history of cold , cough or fever . clinical picture showing the swelling in the left submandibular region examination revealed a swelling of 9 4 cm in size which extended anteriorly 1 cm in close proximity to chin on left side and posteriorly in line with the ear lobe [ figure 2 ] .\nmargins were well - defined and the swelling was firm , fixed to underlying tissues and non tender on palpation .\nno local rise of temperature was seen in the concerned area . left submandibular lymph node was 0.5 cm in size and mildly tender on palpation .\nfew differential diagnoses such as sarcoidosis , sjogren 's syndrome , lymphomas and mikulicz disease were considered .\nsjogren 's syndrome was ruled out as there was no history of dryness . in both sarcoidosis and sjogren 's syndrome\nmikulicz disease is an autoimmune disease and thus was ruled out . swelling seen 2 cm below the ear lobe the following investigations were done : \n fnac gave an impression of chronic non specific lymphadenitis .\nno evidence of cytological atypia seenultra sonography report showed a circumscribed mixed area of 3 1.5 cm in the anterior region of left submandibular gland .\nno evidence of cytological atypia seen ultra sonography report showed a circumscribed mixed area of 3 1.5 cm in the anterior region of left submandibular gland .\nthe patient was further subjected to ct scan of head and neck and the impression was of \n submandibular salivary gland tumourmultiple submental and submandibular lymphadenopthy . \n \n, a diagnosis of benign tumour of the left submandibular gland was given . during excision of the tumour , it was found that whole of the gland was involved .\nso , total submandibular gland excision was done and the specimen was sent for histopathological analysis .\ngross finding revealed a single bit of soft tissue measuring 4 6 2 cm , yellowish red in color , firm in consistency .\n[ figure 3 ] cut sections revealed yellowish to whitish central core surrounded by whitish brown to brownish areas [ figure 4 ] .\nspecimen showing 2 lymph nodes attached to the soft tissue specimen grossed specimen showing yellowish to whitish central core surrounded by whitish brown to brownish areas histopathological examination revealed hematoxylin and eosin ( h and e ) stained sections revealed destruction of salivary gland architecture .\nphotomicrograph showing neoplastic lymphocytes in a follicular pattern.(h&e stain , 100 ) photomicrograph showing neoplastic lymphocytes with hyperchromatic nuclei and scanty cytoplasm .\n( h&e stain , 200 ) based on the histopathological appearances , a provisional diagnosis of low grade lymphoma was made and immunohistochemical profiling was done to confirm the type of lymphoma . the tissue was stained for bcl2 an anti apoptotic marker , cd20 b lymphocyte marker , cd3 which is exclusively a t lymphocyte marker , cytokeratins and ema .\nimmunohistochemistry revealed that the cells were strongly positive for bcl-2 [ figure 7 ] and cd 20 [ figure 8 ] which are both cytoplasmic markers and negative for cd3 [ figure 9 ] .\n( ihc stain , 200 ) photomicrograph showing neoplastic cells expressing strong positivity for cd20 .\n( ihc stain , 100 ) photomicrograph showing neoplastic cells with negative expression for cd3 .\n( ihc stain , 100 ) based on the results of immunohistochemical profiling , a diagnosis of follicular b cell lymphoma was reached .\npatient was referred to higher center where full body mri did not reveal any foci of disease . nevertheless ,\nconsidering the indolent course of this disease , she has been on regular follow up and has not reported with any clinically suspicious changes .\nlymphomas also involve in the descending order of frequency , the submandibular gland ( 30% ) , minor salivary glands and the sub lingual glands .\nthe finding of a lymphoma in a major salivary gland could mean one of two things : either it is part of a disseminated process , or it is the first clinicopathologic evidence of lymphoma .\nin the latter instance , whether the disease originated in the glandular stroma itself or in a para glandular lymph node and then invaded the stroma , the lymphoma is defined as primary , as long as there is no detectable disease outside the salivary gland .\nhyman and wolf have given few criterions for diagnosis of primary lymphoma which are : \n involvement of gland should be the first clinical manifestation of the diseasehistologically , the disease should involve the gland parenchyma and not the adjacent node or soft tissue alonethere should be confirmation of malignant nature of lymphoid infiltrate . \n \ninvolvement of gland should be the first clinical manifestation of the disease histologically , the disease should involve the gland parenchyma and not the adjacent node or soft tissue alone there should be confirmation of malignant nature of lymphoid infiltrate .\nlichenfield et al . , reserved the diagnosis of primary salivary gland lymphoma , when lymphoma has been ruled out elsewhere in the body .\nthe diagnosis of lymphoma in case of a salivary gland swelling is rarely done preoperatively .\neven though the diagnosis of lymphomas , in the algorithm of diagnosis of salivary gland swelling is rare , nevertheless , it should be considered .\nfollicular lymphoma , although unpredictable and often associated with a prolonged course shows indolent behavior .\novertime , there is a tendency to transform to a higher grade of lymphoma , usually diffuse large cell lymphoma . although various treatment modalities exist , none are curative and very few have been shown to prolong survival .", "answer": "lymphomas are neoplastic diseases of lymph nodes . \n lymphoma of the salivary gland is rare accounting for less than 5% of lymphomas overall . \n furthermore , lymphomas arising in the submandibular gland are reported to comprise 916% of all salivary gland lymphomas . among lymphomas originating from salivary glands , \n the ratio of follicular lymphoma is very low . \n they can also be seen in the lymph nodes of the salivary glands which is an uncommon presentation . here , \n we present a case follicular lymphoma which presented as a salivary gland tumour .", "id": 314} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmalaria is one of the world 's leading killers , having a greater morbidity and mortality than any other infectious diseases , with greater mortality in children and pregnant women .\nmalaria is caused by a parasite of the genus plasmodium and transmitted by female anopheles mosquito .\nrenal damage and hemolysis induced by malaria , especially p. falciparum and p. vivax , occur between 2 and 6% of hospitalized patients with a mortality that can reach up to 50% .\nthe pathogenesis of renal damage and hemolysis during malaria infection is multifactorial and not well characterized , but several studies suggest involvement of cytoadherence of parasitized erythrocytes and proinflammatory response as well as oxidative stress [ 35 ] .\nthis has prompted research towards the discovery and development of new , safe , and affordable antihemolysis drugs during malaria infection . in this\nplant extracts are commonly investigated in several parts of the world for their possible activities for using in malaria [ 710 ] . moreover , many studies recently endorsed the use of traditional medicinal plants to treat diseases [ 1116 ] .\nthis plant is widely found in asia and southeast asia including thailand and used for general weakness , malaria fevers , and chronic rheumatism .\nthis result is confirmed by the existence of phenolic and flavonoids such as catechin , luteolin , and borapetoside .\nthese are responsible for high antioxidant activity and other activities including anti - inflammation , antimicrobials , and anticancer [ 1921 ] .\nthe antioxidant properties of t. crispa stem extract make it useful for the treatment of diseases resulting from oxidative stress such as cardiovascular disease , cancer , liver damage , and renal disease .\nit also has been used as an antimalarial agent in vivo [ 22 , 23 ] .\nhowever , it has not been reported yet to use t. crispa stem extract to treat renal damage and hemolysis induced malaria infection .\nhence , the present study was aimed to investigate the protective effects of t. crispa stem extract on renal damage and hemolysis induced by p. berghei infection in mice .\nfresh stems of tinospora crispa were collected from natural environment in suphanburi province , thailand , from march to april 2015 .\nstems were minced into small pieces and dried in hot - air oven at 60c for 72 h , after which the dried plants were ground and then extracted in distilled water at the proportion of 1 : 10 ( w / v ) using microwave at 360 w for 5 min .\nthe extract was filtered through whatman number 1 filter paper , and evaporation was then performed to remove solvent .\npowder extract was dissolved in distilled water to obtain appropriate doses for using in mice and volume should not be higher than 1 ml .\ndrug doses , expressed in mg / kg of body weight , were adjusted at the time of administration according to the weight of the mice .\npathogen - free , female icr mice , aged 46 weeks and weighting 2530 g , were purchased from the national laboratory animal center , mahidol university , bangkok , thailand .\nthey were kept at 2225c with 12 h light / dark cycle and given standard mouse pellet and water ad libitum .\nall procedures of the animal experiments were approved by the ethical committee on animal experimentation , faculty of medical technology , western university . \n\npbanka was kept alive by intraperitoneal ( ip ) passage of 1 10 parasitized erythrocytes in nave mice .\nin addition , hematocrit ( % hct ) was also monitored by collecting tail vein into heparinized hematocrit tubes and centrifuged at 10,000 g for 10 min .\nblood urea nitrogen ( bun ) and creatinine were used as indicators of renal function .\nmouse blood was collected from tail vein into heparinized hematocrit tubes and centrifuged at 10,000 g for 10 min .\nplasma was subsequently collected and used as subjects for measurement of bun and creatinine using an available commercial kit ( biosystems ) according to manufacturer 's instruction .\nprotective effect of aqueous crude extract of t. crispa on renal damage and hemolysis during malaria infection was done based on standard 4-day suppressive test .\ngroups of icr mice ( 5 mice of each ) were randomly divided , and infection was then performed with 1 10 parasitized erythrocytes of pbanka by ip injection .\ntwo hours after infection , they were given orally by gavage with 500 , 1000 , and 2000 mg / kg of the extracts and every 24 h twice a day for 4 consecutive days .\nthree control groups were used ; normal controls were given either distilled water or the extract while untreated control was given only distilled water . on day 4 of experiment , tail blood was collected to assess hemolysis by measurement of % hct .\nparasitemia was first detectable on day 1 after infection with a parasitemia of 0.5% and reached 65% on day 10 ( figure 1(a ) ) .\nnext , we observed that bun and creatinine levels were markedly increased in infected mice , and first significant ( p < 0.05 and p < 0.001 ) increases were found on day 4 after infection ( figures 1(b ) and 1(c ) ) .\nadditionally , we also observed progressive decreases of % hct in infected mice in response to the presence of parasitemia ( figure 1(d ) ) .\nit was found that t. crispa stem extract showed protective effect on renal damage induced by pbanka infection in mice , and the highest activity was found at dose of 2000 mg / kg of extract treated group ( figure 2 ) .\nthe bun and creatinine levels were increased significantly ( p < 0.01 and p < 0.001 , resp . ) by malaria infection ( untreated group ) and infected mice treated with 500 mg / kg of the extract , compared to normal control .\ninterestingly , after oral administration of t. crispa stem extract , bun and creatinine levels declined significantly ( p < 0.01 and p < 0.001 , resp . ) , especially at doses of 1000 and 2000 mg / kg , compared to untreated control .\nhowever , t. crispa stem extract could not be able to decrease parasitemia levels . \n\nt. crispa stem extract exerted antihemolytic effect against pbanka infected mice . as shown in figure 3 ,\nhemolysis was observed in untreated control and infected mice treated with 500 mg / kg of the extract as indicated by decreasing of % hct with significance ( p < 0.01 ) , compared to normal control .\ninterestingly , % hct was significantly ( p < 0.01 ) increased in infected mice treated with 1000 and 2000 mg / kg of the extract , compared to untreated control .\nthe highest effect was found at dose of 2000 mg / kg of the extract .\nmoreover , prolonged survival time of infected mice treated with this extract was also observed .\nin the current study , we provide evidence that describes the protective effect of t. crispa stem extract on renal damage and hemolysis induced by p. berghei infection in mice .\nthe onset of renal damage and hemolysis in icr mice infected with pbanka come out from day 4 after infection and the incidence of renal damage and hemolysis were confirmed through manifestations such as increasing of bun and creatinine as well as decreasing of % hct in infected mice .\nrenal damage and hemolysis are proposed to be a consequence of parasite adhesion and exacerbated immune response against products of oxidative stress released during infection .\nin addition , parasitized erythrocyte sequestration at the microvascular site of renal has also been discussed to induce renal damage .\nthe destruction of erythrocytes during blood stage infection accumulates high levels of toxic - free heme that has ability to induce oxidative stress from production of hydroxyl radicals via fenton / haber - weiss reaction .\nmoreover , heme - derived oxidative stress is considered to be a main factor in the iron - induced lipid peroxidation resulting in the formation of oxidized ldl .\ntherefore , these conditions derived by blood stage of infection result in renal damage and hemolysis .\nhowever , protective effects of renal damage and hemolysis induced by malaria infection were found in infected mice treated with t. crispa stem extract .\npolyphenols and flavonoids show high antioxidant and anti - inflammation properties and then protect oxidative stress development .\nt. crispa stem extract has been shown to contain high amounts of polyphenols and flavonoids .\nthus , the potent antioxidant activity of this extract might play a central role in protecting renal damage and hemolysis from oxidative stress induced by malaria infection .\nmoreover , t. crispa stem extract has been reported to have antimalarial activity against p. yoelii infection in mice .\nso , antimalarial activity to inhibit p. berghei growth and subsequently inhibit renal damage and hemolysis might also be mentioned .\ntaken together , our results suggest that t. crispa stem extract shows protective effects against p. berghei - induced renal damage and hemolysis .\nappropriate pharmaceutical strategies might now be devised to increase the low bioavailability of this extract and to protect against rapid in vivo metabolic transformation , in such a way to make them more amenable as alternative antimalarial drug in combination therapies .", "answer": "renal damage and hemolysis induced by malaria are associated with mortality in adult patients . \n it has been speculated that oxidative stress condition induced by malaria infection is involved in its pathology . \n thus , we aimed to investigate the protective effects of tinospora crispa stem extract on renal damage and hemolysis during plasmodium berghei infection \n . t. crispa stem extract was prepared using hot water method and used for oral treatment in mice . \n groups of icr mice were infected with 1 107 parasitized erythrocytes of p. berghei anka by intraperitoneal injection and given the extracts ( 500 , 1000 , and 2000 mg / kg ) twice a day for 4 consecutive days . to assess renal damage and hemolysis , blood urea nitrogen ( bun ) , creatinine , and hematocrit ( % hct ) levels \n were then evaluated , respectively . \n malaria infection resulted in renal damage and hemolysis as indicated by increasing of bun and creatinine and decreasing of % hct , respectively . \n however , protective effects on renal damage and hemolysis were observed in infected mice treated with these extracts at doses of 1000 and 2000 mg / kg . in conclusion , \n t. crispa stem extract exerted protective effects on renal damage and hemolysis induced by malaria infection . \n this plant may work as potential source in the development of variety of herbal formulations for malarial treatment .", "id": 315} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsciatic hernias are one of the rarest types of hernia and often pose diagnostic difficulty to clinicians . imaging is often required to confirm the diagnosis and usually involves computed tomography ( ct ) or magnetic resonance imaging ( mri ) . to our knowledge , we report the 115th case of sciatic hernia in the literature who had a falsely negative ct but had the diagnosis confirmed using ultrasonography .\nan 80-year - old lady was referred to the on - call surgical team by her gp with a 3-week history of a right - sided swelling of the buttock .\nshe had a past medical history of hypertension , osteoarthritis and pemphigus vulgaris and a past surgical history of a perianal abscess requiring incision and drainage .\nshe was allergic to penicillin and took regular oral betamethasone , xylometazoline nasal spray and topical aqueous cream .\nshe did not consume alcohol , was a non - smoker and lived in warden - controlled accommodation . on examination , her cardiac , respiratory and abdominal examinations were normal .\ndigital rectal examination revealed a non - tender stool - filled rectum with no palpable masses . on standing , a swelling on the medial aspect of the right buttock became apparent which was easily reducible , had audible bowel sounds and a positive cough impulse .\nshe was reviewed by the on - call consultant who discharged her with a working diagnosis of possible obturator hernia , with a plan for an outpatient ct of her pelvis and follow - up in clinic .\nct scan of the pelvis did not identify a cause for the swelling ( fig . 1 ) .\ndue to the positional nature of the swelling , a gluteal ultrasound was organized , which revealed a large colonic sciatic hernia ( fig . 2 ) .\nas the patient had minimal symptoms and was not keen for surgical intervention , a plan for conservative management was agreed and the patient was discharged from clinic . \n\nfigure 1:ct of the patient 's pelvis demonstrating a normal right sciatic foramen ( arrowed ) . \n\nus hip rt : confirms reducible herniation of colon in the right sciatic region into the buttock. ) ct of the patient 's pelvis demonstrating a normal right sciatic foramen ( arrowed ) .\nhip rt : confirms reducible herniation of colon in the right sciatic region into the buttock. )\nsciatic hernias are one of the rarest types of hernia and often pose diagnostic difficulty to the clinician .\na sciatic hernia is defined as herniation of intraperitoneal contents through either the greater or lesser sciatic foraminae ( fig . \nthe majority of sciatic hernias are found in women ( 77% ) with more than one - third of these being aged 60 or over .\nthe contents are variable and hernias containing ovaries , ureters , bladder , small and large intestine , omentum and dermoid cysts have been reported [ 16 ] .\nhalf of patients report non - specific abdominal or pelvic pain and one third have a mass on clinical examination .\nsciatica , intestinal obstruction , urinary sepsis and hydronephrosis have also been described [ 15 ] .\ndiagnostic laparoscopy or laparotomy is often required to fully evaluate the sac contents and to repair the defect [ 2 , 3 , 5 ] . in symptomatic patients ,\nsurgical repair is indicated due to the high risk of bowel strangulation [ 1 , 3 ] . \n\nfigure 3:pelvis demonstrating the greater ( red ) and lesser ( green ) sciatic foraminae .\ndiagnosis by clinical examination alone is possible in only the minority of cases and imaging is frequently used to confirm the suspicion of sciatic hernia .\ncommonly used imaging modalities are computerized tomography ( ct ) [ 25 ] and mri [ 3 , 4 ] , particularly if the sciatic nerve is thought to be involved .\ncurrently , the most commonly used imaging modality of choice is a ct scan with the patient supine . however ,\nif the hernia is only apparent in a dependent position , this can produce a false - negative result , as in our case .\nthe benefit of ultrasound is that it allows for real - time positional assessment of the region of interest , to reduce the risk of missing this rare but significant hernia .\ndue to their rarity , sciatic hernias are often not considered in the differential diagnosis .\nthe authors recommend that all patients presenting with non - specific abdominal or pelvic pain associated with a gluteal swelling should have sciatic hernia considered amongst their differential diagnosis . for patients\nin which there is a high degree of clinical suspicion for a sciatic hernia and a negative ct , the use of ultrasonography for positional defects may be a useful aid to confirming the suspected diagnosis .", "answer": "sciatic hernias are one of the rarest types of hernia and often pose diagnostic difficulty to clinicians . we report a case of an 80-year - old lady with a sciatic hernia who had a falsely negative computed tomography ( ct ) but was found to have a colonic hernia on ultrasonography . \n the authors recommend that for patients in which there is a high degree of clinical suspicion for a sciatic hernia and a negative ct , ultrasonography may be considered as a useful imaging modality to confirm the diagnosis .", "id": 316} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a recent issue of critical care , we presented a series of 13 patients undergoing post - cardiotomy extracorporeal membrane oxygenation ( ecmo ) with bivalirudin - based anticoagulation .\nafter this series , we satisfactorily continued this experience , reaching about 20 patients treated .\nhowever , we think that a word of caution should be added to our recently published experience . owing to its pharmacological profile\n, bivalirudin is rapidly cleaved by proteolytic enzymes , and its half - life is about 25 minutes when the renal function is normal .\nthe use of bivalirudin for cardiopulmonary bypass ( cpb ) and ecmo is a feasible option .\nhowever , it is recommended that , during cpb , blood stagnation in the circuit be avoided because the rapid cleavage of bivalirudin may result in thrombosis .\nthe ecmo circuit is devoid of a reservoir , and therefore blood stagnation is usually not a circuit- related problem .\nconversely , under some circumstances , the cardiac chambers may act as a ' natural reservoir ' , which entails blood stagnation and the risk for spontaneous intracardiac thrombosis .\nthis is particularly true in the case of a very large right or left atrium with insufficient venous drainage or the case of very poor ventricular systolic function with intraventricular blood stagnation . to avoid this condition\n, we think that maintaining a partial ecmo support , leaving a minimal degree of intracardiac blood flow , may be a reasonable choice .\nthis may be checked by echocardiographic view of heart valve movement or simply by the observation of some degree of pulsatile arterial blood pressure .\nwe think that , in the event of echocardiographic evidence of a ' smoke effect ' within one or more cardiac chambers , bivalirudin should be replaced by standard heparin anticoagulation .\nintracardiac thrombus formation during ecmo with heparin anticoagulation has been described as well , but the pharmacokinetic properties of heparin may limit the risk of thrombus formation due to blood stagnation .", "answer": "bivalirudin has been proposed as the sole anticoagulant in patients under extracorporeal membrane oxygenation ( ecmo ) or cardiopulmonary bypass . \n owing to the pharmacodynamic properties of bivalirudin , areas of blood stagnation should be carefully avoided in order to limit the risk of thrombosis . \n the ecmo circuit has no reservoir and is usually devoid of blood stagnation areas . \n conversely , under some circumstances , intracardiac blood stagnation areas may exist . in this case \n , there is a potential risk for the spontaneous formation of an intracardiac thrombus . \n we suggest that , under bivalirudin anticoagulation , a minimal degree of intracardiac blood flow with left heart valve movement is allowed .", "id": 317} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe use of bleaching materials both hydrogen peroxide and carbamide peroxide has become an attractive procedure in the dental clinic .\nfurthermore , the use of fluoride - releasing glass ionomer as a dental restorative material has also become popular .\nthe situation where these materials interact within the oral cavity during the bleaching process can occur frequently ; thus , understanding their reaction is important .\nthe bleaching process is believed to occur through oxidation by hydroxyl radicals that are generated from the bleaching agent . with clinically favorable and safe aspects for patients ,\nseveral studies have shown the effectiveness of bleaching agents on dental restorative materials and teeth with regard to surface hardness , or other modifications . during setting of glass ionomer ,\nfluoride ions are produced from strong soluble aluminofluoride complexes like alf . when a fully set glass ionomer is exposed to neutral aqueous solutions , it absorbs water and releases ions such as sodium , silica , calcium , and fluoride .\ntwo processes occur during fluoride release : a fast elution process during the early periods , and a long - term diffusive process .\nit is also influenced by experimental factors , i.e. , storage media , frequency of change of the storage solution , composition and ph - value of saliva , plaque , and pellicle formation . in vitro ,\nfluoride release increases in acidic media ; this was explained by the fact that decreasing ph increases the dissolution of the material leading to a higher fluoride level in acidic immersion .\nthereby , the proportion of free fluoride to bound fluoride was higher under acidic than under neutral conditions . when hydrogen peroxide is stored , an acidic ph must be maintained to extend the shelf life .\nthey found that at home bleaching products have a ph range from 5.66 to 7.3 .\nwhile they found ph of in - office bleaching system were lower and ranged from 3.6 to 6.5 .\nwhen hydrogen peroxide interacts with dental materials , it decomposes to form hydroxyl radical intermediates and finally to form water and oxygen . also , carbamide peroxide will dissociate to h2o2 , co2 , urea and nh3 , and then h2o2 will decompose again to water and oxygen finally . those chemical ingredients may affect the fluoride release of glass ionomer restoratives .\nthe purpose of this study was to evaluate the effect of vital bleaching on the fluoride release of various types of glass ionomer restorations . also , to compare the fluoride release of various types of glass ionomer restorations .\ntwo vital bleaching commercial products and three types of glass ionomer restorative materials were selected for this study .\nbleaching materials used were opalescence xtra boost ( 38%hydrogen peroxide with ph of 7 ) and opalescence quick ( 35%carbamide peroxide with ph of 6 ) both manufactured by ultradent ( inc .\nglass ionomer materials used were ketac fil ( conventional glass ionomer ) , photac fil ( resin modified glass ionomer ) , and f2000 ( poly acid modified composite resin ) manufactured by 3 m ( espe , st paul , usa ) .\nthirty disk shaped specimens ( 5 mm in diameter and 2 mm in thickness ) were prepared for each brand of glass ionomer .\nthe mold was sandwiched between two glass plates to allow setting of glass ionomer under pressure .\ncapsules of ketac fil were activated then triturated according to manufacturer instructions for 15 s , injected in the holes of the mold in one increment .\nthe mold was filled to slight excess , the specimen 's top surface was covered by a mylar strip and a glass slide was secured to flatten the surface and pressed with standard load 500 mg over the mold then left for setting .\ncapsules of both photac fil and f2000 were triturated according to manufacturer instructions for 15 s and injected into holes , covered with glass slide , and light cured for 40 s per each side using a light source ( pencure , j morita mfg corp . ,\neach disk specimen was removed from the mold by separating its two halves and placed in a numerated plastic tube containing 5 ml of distilled water , tightly sealed with a cap .\nthe specimens were incubated at 37c during the whole experimental period ( 3 months ) . after 24 h\neach group was further subdivided into three sub - groups , 10 samples for each group .\nthe first sub group was a control group , the second sub group was bleached with opalescence xtra ( ox ) , and the last one was bleached with opalescence quick ( oq ) .\nsecond and third subgroups were bleached with the two bleaching agents ox and oq according to their manufacturer instructions , every sample was covered with 2 ml of the bleaching material and left for 1 h. disks were then washed thoroughly with distilled water , and then returned back to their tubes . control samples ( the first sub group ) returned back to the tubes after water in the tubes of all subgroups being changed with new 5 ml of distilled water .\nthe measurements were performed after 1 week , 1 month , and 3 months and every time , samples were rinsed with distilled water and water in the tubes changed with new 5 ml of distilled water .\nfluoride release measurements were performed using specific ion electrode ( ph meter f-22 horiba ) after adding total ionic strength adjustment buffer ( tisab ) solution .\ndata were recorded and analyzed by using one - way analysis of variance ( anova ) followed by bonferroni multiple comparison post hoc test at the significance level of = 0.05 .\nthe analysis of variance was carried out considering the factors ( material , time , and interaction ) .\ndata were recorded and analyzed by using one - way analysis of variance ( anova ) followed by bonferroni multiple comparison post hoc test at the significance level of = 0.05 .\nthe analysis of variance was carried out considering the factors ( material , time , and interaction ) .\ntime had highly significant effect on fluoride released from all glass ionomer materials under test at p < 0.05 [ table 1 ] . ketac fil showed initial burst in fluoride release in the first week ( t1 ) of 58.6 ppm , then concentration of fluoride decreased sharply after 1 month ( t2 ) of 10.94 ppm .\nafter 3 months ( t3 ) , the concentration of fluoride decreased again of 5.94 ppm [ figure 1 ] .\nfor photac fil , time had only a significant effect on fluoride release [ figure 2 ] .\nfluoride release of f2000 was also affected by time and this was highly significant [ figure 3 ] .\neffect of time on fluoride release for three types of glass ionomer materials mean fluoride concentration of ketac fil as affected by time .\nstudying fluoride release as affected by the type of glass ionomer material regardless the type of bleaching and time ; the result was highly significant at p < 0.01 . comparing the three brands ;\nthere was no significant difference at p > 0.05 in fluoride release considering only the type of bleaching regardless type of glass ionomer and time .\na significant increase in the mean fluoride released from ketac fil bleached with opalescence xtra compared to the untreated control group and the group bleached with opalescence quick . for photac fil ,\nopalescence xtra caused slight increase in fluoride release while no significant differences in fluoride release were found after bleaching f2000 .\naccording to the type of bleaching and the time , highly significant difference was found between the tested materials at p < 0.01 .\nthe use of hydrogen peroxide or peroxide releasing agents , such as carbamide peroxide or sodium perborate for brightening discolored teeth has become a popular treatment modality .\nglass ionomers are often used for restoration of cervical lesions because of bonding to tooth structure and releasing fluoride .\nthe influence of various bleaching agents on physical properties , surface morphology , and color of different restorative materials has been investigated in several in vitro studies simulating the clinical situation as closely as possible . in our study\n, it was found that the effect of bleaching on fluoride release of glass ionomer is material dependent depends on the type of bleaching material and the type of glass ionomer .\nmoreover , time factor was found to have an essential role . the high initial fluoride \neffect was only observed with ketac fil and photac fil after 1 week and dropped sharply by the second period after 1 month .\nthis finding is in agreement with previous studies which may be attributed to the high instability and erosion of glass ionomer during the early setting period .\nthose studies have shown that the cumulative amount of fluoride ions released from glass ionomer cements , after a short period of time , is diffusion controlled and follows a decreasing gradient , which is linear to the square root of time .\nthereby , the initial high amounts of fluoride rapidly decrease after 24 - 72 h and plateaued to a nearly constant level within 10 - 20 days . in contrast\nsignificant difference in fluoride release was found between both ketac fil , photac fil , and f2000 but no significant difference was found between ketac fil and photac fil .\nranking the three brands according to their fluoride release at the first period of the test ; ketac fill was the material with the greatest rate of fluoride release , followed by photac fill then f2000 .\nthis difference can be explained by the composition of the compomer brands , which exhibited higher fluoride content and contained smaller fillers , which might lead to a better reactivity due to the greater size of the specific surface .\nhowever , it was material dependent and depended on the type of bleaching , type of glass ionomer , and time .\nthis effect was highly significant by the first week and did not prolong to other periods of the test .\n, 1997 who stated that the main daily release of fluoride did not differ significantly between bleaching agent and control .\nthe reason for the contrasting results between the two studies may be attributed to different concentrations of bleaching agents used in both studies .\nopalescence quick has no significant effect on the fluoride release of the three materials . excluding the ph factor ( as both bleaching materials are close to neutral ) , this can be attributed to that : carbamide peroxide degrades into approximately one - third hydrogen peroxide and two - thirds urea , and hydrogen peroxide can be considered its active ingredient .\nthe hydrogen peroxide content in opalescence quick is therefore much lower than that in opalescence xtra .\nalso opalescence quick has more complicated steps of break down to free radicals than opalescence xtra .\nthis result was in agreement with lee , et al . , 2002 who concluded that hydrogen peroxide has a similar effect on the fluoride release from compomers compared to the case of distilled water .\nopalescence xtra ( ox ) increased fluoride release from conventional and resin - modified glass ionomers in the first week while the effect faded by time .\nopalescence quick ( oq ) had no significant effect on the fluoride release of the three materials .", "answer": "objective : this study was designed to evaluate the effect of two bleaching agents on the fluoride release of three types of glass ionomer materials.materials and methods : a total of 90 specimens of the tested materials ( ketac fil , photac fil and f2000 ) were prepared by a split teflon ring with an internal diameter of 5 mm and thickness of 2 mm . \n the tested materials were applied and bleached according to manufacturer instructions . \n fluoride release measurements were made by using specific ion electrode.results:results revealed that bleaching with opalescence xtra caused little increase in fluoride release from ketac fil and photac fil but has no effect on f2000 . \n however , opalescence quick had no significant effect on the three tested materials.conclusions:bleaching effect on fluoride release is material dependent and time has a significant role on fluoride release .", "id": 318} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nearly atherogenesis is characterized by the recruitment of circulating leukocytes ( e.g. , monocytes / macrophages and t - lymphocytes etc . ) into artery wall , the formation of foam cells in the vessel intima , leading to the development of atherosclerotic lesions .\nthe inflammatory responses in the atherosclerotic lesions play a crucial role to promote plaque rupture and thrombosis in the late progression of atherosclerosis , leading to myocardial infarction and strokes ( libby , 2002 ) .\nthe rupture - prone plaque is featured by a large lipid core and accumulation of inflammatory cells including macrophages and t - lymphocytes ( mann & davies , 1996 ) . a family of matrix metalloproteinases ( mmps ) , which are proteolytic enzymes secreted by the inflammatory cells , play a pivotal role in degrading extracellular matrix and plaque rupturing ( newby , 2005 ) .\nchemokines , a superfamily of chemotactic cytokines , not only cause the recruitment of leukocytes into the arterial wall , but also influence atherosclerotic plaque stability by enhancing mmps releases ( reape & groot , 1999 ; sheikine & hansson , 2004 ) , and thus play a crucial role in both the initiation and the progression of atherosclerosis .\nleukotactin-1 ( lkn-1/ccl15 ) , a new member of the human cc chemokine family , is a potent chemoattractant for leukocytes , and it is implicated in inflammatory pathologies including atherosclerosis . our previous study and\nothers have shown that the levels of lkn-1/ccl15 expression are markedly up - regulated in macrophage - derived foam cells and in human atherosclerotic lesions ( lee et al . , 2002 ; yu et al . , 2004 ) , and moreover , the proatherogenic mediators such as oxidized lipoprotein and oxidative stress markedly upregulte lkn-1/ccl15 gene expression and protein release from the foam cells ( yu et al . , 2004 ) , indicating lkn-1/ccl15 plays a role in the initiation of atherogenesis .\nhowever , it remains unclear whether lkn-1/ccl15 is associated with the progression of atherosclerosis . in the present study\n, we investigated whether lkn-1/ccl15 can enhance mmp-9 release from macrophages and/or foam cells , which influence plaque rupture .\nour data demonstrated that lkn-1/ccl15 enhanced mmp-9 protein release from human macrophages and macrophage - derived foam cells , indicating that lkn-1/ccl15 may be associated with the vulnerability of plaque rupture in the late stage of atherosclerosis .\nthe cells were plated at a density of 5 10 cells / ml in the medium containing phorbol myristate acetate ( pma , sigma ) at 10 m for 48 h to induce their differentiation into macrophages .\nafter washings twice with hbss without ca and mg , the pbmcs were then suspended in 10% fbs containing rpmi and incubated for 60 min at 37 to let the monocytes attach to the culture dish .\nthe attached monocytes were harvested by vigorous pipetting and plated at a density of 5 10 cells / ml in the medium containing pma at 10 m for 48 h to induce their differentiation into macrophages .\nhuman low density lipoprotein ( ldl ) ( d = 1.006 - 1.063 ) was separated from freshly drawn normal plasma sample by sequential ultracentrifugation and extensively dialyzed at 4 against 0.15 mol / l nacl and 0.01% edta .\nafter edta was removed , ldl was subjected to oxidative modification by incubation with cu ( 5 m cuso4 , 16 h at 37 ) .\nthen cu was removed by extensive dialysis ( yu et al . , 2004 ) .\nthe extent of modification was assessed by the determination of electrophoretic mobility on agarose gels . in agarose gel electrophoresis ,\noxldl was stored at 4 and was used within 4 weeks of preparation . to prepare macrophage - derived foam cells ,\nhuman thp-1 cells were plated at a density of 5 10 cells / ml in the medium containing pma at 10 m for 48 h to induce their differentiation into macrophages , and then the cells were treated with human oxidized ldl ( 25 g / ml ) for 4 days ( yu et al . , 2004 ) .\nthe gelatinolytic activities of mmp-9 in the conditioning culture medium were assayed by electrophoresis on 10% polyacrylamide gels containing 1 mg / ml gelatin at 4. page gels were run at 120 v , washed in 2.5% triton x-100 for 1 h , and then incubated for 16 h at 37 in activation buffer ( 50 mm tris - hcl , ph 7.5 , 10 mm cacl2 ) . after staining with coomassie blue ( 10% glacial acetic acid , 30% methanol and 1.5% coomassie brilliant blue ) for 2 - 3 h , the gel was destained with a solution of 10% glacial acetic acid , and 30% methanol without coomassie blue for 1 h. white lysis zones indicating gelatin degradation were revealed by staining with coomassie brilliant blue r-250 .\nthe cells were plated at a density of 5 10 cells / ml in the medium containing phorbol myristate acetate ( pma , sigma ) at 10 m for 48 h to induce their differentiation into macrophages .\nafter washings twice with hbss without ca and mg , the pbmcs were then suspended in 10% fbs containing rpmi and incubated for 60 min at 37 to let the monocytes attach to the culture dish .\nthe attached monocytes were harvested by vigorous pipetting and plated at a density of 5 10 cells / ml in the medium containing pma at 10 m for 48 h to induce their differentiation into macrophages .\nhuman low density lipoprotein ( ldl ) ( d = 1.006 - 1.063 ) was separated from freshly drawn normal plasma sample by sequential ultracentrifugation and extensively dialyzed at 4 against 0.15 mol / l nacl and 0.01% edta .\nafter edta was removed , ldl was subjected to oxidative modification by incubation with cu ( 5 m cuso4 , 16 h at 37 ) .\nthen cu was removed by extensive dialysis ( yu et al . , 2004 ) .\nthe extent of modification was assessed by the determination of electrophoretic mobility on agarose gels . in agarose gel electrophoresis ,\nto prepare macrophage - derived foam cells , human thp-1 cells were plated at a density of 5 10 cells / ml in the medium containing pma at 10 m for 48 h to induce their differentiation into macrophages , and then the cells were treated with human oxidized ldl ( 25 g / ml ) for 4 days ( yu et al . , 2004 ) .\nthe gelatinolytic activities of mmp-9 in the conditioning culture medium were assayed by electrophoresis on 10% polyacrylamide gels containing 1 mg / ml gelatin at 4. page gels were run at 120 v , washed in 2.5% triton x-100 for 1 h , and then incubated for 16 h at 37 in activation buffer ( 50 mm tris - hcl , ph 7.5 , 10 mm cacl2 ) . after staining with coomassie blue ( 10% glacial acetic acid , 30% methanol and 1.5% coomassie brilliant blue ) for 2 - 3 h , the gel was destained with a solution of 10% glacial acetic acid , and 30% methanol without coomassie blue for 1 h. white lysis zones indicating gelatin degradation were revealed by staining with coomassie brilliant blue r-250 .\nthe present study has demonstrated that lkn-1/ccl15 enhances mmp-9 protein release by macrophages and macrophages - derived foam cells , indicating that lkn-1/ccl15 may play a role in the plaque rupture of the atherosclerotic lesions .\nmacrophages , which are abundant in ruptured atherosclerotic plaques , express multiple mmps , weakening the plaque and making it rupture prone ( boyle , 2005 ) . among mmps , mmp-9 ( 92-kda gelatinase b ) , which is a prevalent form expressed by activated macrophages and foam cells , is found in human coronary atherosclerotic lesions ( galis & khatri , 2002 ; pasterkamp et al . , 2000 ) .\nwe found that lkn-1 significantly activated human thp-1 monocytes - derived macrophages and human pbmc - derived macrophages to release mmp-9 ( fig . 1a and 1b ) .\nit has been shown that the circulating levels of lkn-1 are increased in plasma of atherosclerotic patients , and lkn-1 stimulates endothelial cells to release intracellular adhesion molecule-1 ( yu et al . ,\n2004 ) . since mmp-9 is required for monocyte infiltration through endothelium from blood , lkn1/ccl15 action on macrophages to release mmp-9 may accelerate the recruitment of macrophages into the atherosclerotic lesions .\nit has been shown that the expression levels of chemokine genes such as monocyte chemoattractant protein-1 ( mcp-1 ) and interleukin-8 ( il-8 ) are upregulated in human atherosclerotic lesions and they are associated with plaque rupture by activating endothelial cells and smooth muscle cells to release mmps ( kodali et al .\natherosclerotic lesions consist of mainly macrophages and lipid - laden foam cells , and thus excessive production of mmp-9 by lkn-1/ccl15 from macrophages and macrophage - derived foam cells in the lesions may accelerate the destabilization and rupture of the fibrous cap of the atherosclerotic plaque .\nour data demonstrated that lkn-1 markedly enhanced the production of mmp-9 from macrophage - derived foam cells ( fig .\nwe have previously shown that proatherogenic mediators enhance lkn-1/ccl15 release from macrophages and macrophage - derived foam cells ( yu et al . , 2004 ) .\ntherefore , it can be postulated that macrophages and macrophage - derived foam cells in atherosclerotic lesions may enhance the local concentration of lkn-1 in the lesions , and lkn-1/ccl15 subsequently stimulate the macrophages / foam cells per se to secrete mmp-9 , indicating that lkn-1/ccl15 action on macrophages and foam cells to release mmp-9 may contribute to plaque destabilization in the progression of atherosclerosis . in conclusion , lkn-1/ccl15 enhanced mmp-9 protein secretion from thp-1 monocytic cells - derived macrophages , human pbmc - derived macrophages , and thp-1 macrophage - derived foam cells in a dose dependent manner . considering the association of mmp-9 in plaque rupture , our findings suggest that lkn-1/ccl15 could be associated with plaque destabilization in the progression of atherosclerosis . lkn-1/ccl15 may be a useful target for the management of atherosclerosis .\nfurther studies are needed to elucidate the inhibitory effect of phytochemicals or food factors on lkn-1/ccl15 release from macrophages / foam cells .", "answer": "atherosclerosis is characterized by a chronic inflammatory disease , and chemokines play an important role in both initiation and progression of atherosclerosis development . \n leukotactin-1 ( lkn-1/ccl15 ) , a new member of the human cc chemokine family , is a potent chemoattractant for leukocytes . \n our previous study has demonstrated that lkn-1/ccl15 plays a role in the initiation of atherosclerosis , however , little is currently known whether lkn-1/ccl15 is associated with the progression of atherosclerosis . \n matrix metalloproteinases ( mmps ) in human coronary atherosclerotic lesions play a crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture . in the present study \n , we examined whether lkn-1/ccl15 modulates mmp-9 release , which is a prevalent form expressed by activated macrophages and foam cells . human thp-1 monocytic cells and/or human peripheral blood monocytes ( pbmc ) were treated with phorbol myristate acetate to induce their differentiation into macrophages . \n foam cells were prepared by the treatment of thp-1 macrophages with human oxidized ldl . \n the macrophages and foam cells were treated with lkn-1/ccl15 , and the levels of mmp-9 release were measured by gelatin zymography . lkn-1/ccl15 \n significantly enhanced the levels of mmp-9 protein secretion from thp-1 monocytic cells - derived macrophages , human pbmc - derived macrophages , as well as macrophage - derived foam cell in a dose dependent manner . \n our data suggest that the action of lkn-1/ccl15 on macrophages and foam cells to release mmp-9 may contribute to plaque destabilization in the progression of atherosclerosis .", "id": 319} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nworksites in glass and metal works , foundries , rolling mills , in the vicinity of hardening furnaces , rotary kilns in the cement industry , high - temperature laboratory furnaces , as well as firefighting , are associated , in addition to common mechanical hazards ( e.g. , due to splashes of molten metals and slag ) , sparks and direct contact with open fires , with hazards caused by emission of harmful optic radiation within the visible ( vis ) and infrared ( ir ) spectrum range .\nexcessive exposure to ir radiation leads to dryness of the mucous membranes , burns of the eyeball and development of cataracts .\nprotection against thermal hazards due to excessive amounts of ir radiation reaching the eyes is provided by protective optic filters installed in spectacles , goggles or face protections . besides protecting the user against hazardous ir radiation\n, such filters should ensure that the object / area of work can be seen clearly . if the level of ir radiation is very high ,\nthe use of filters reflecting radiation is recommended , as it allows the temperature increase in the filter itself to be reduced .\nthe filters currently used for the protection of the face and eyes against hazardous ir radiation are of metallic reflective type , made of glass or organic material ( mainly polycarbonate ) bases coated with a single metallic layer for reflectance of ir radiation or absorption filters .\nabsorption filters are manufactured from dyed glass obtained in a mass staining process by introduction of a factor modifying the radiation within the vis and near infrared ( nir ) spectrum range passing through the filter .\nthe effect of a protective optical filter obtained as a result of this process is based on absorption of a large proportion of optic radiation , whereas only a small proportion of radiation the filter is exposed to is reflected .\nthis is an undesirable phenomenon , contributing to deterioration of the filter user 's comfort .\nreflective metallic filters are obtained by deposition of a metallic layer of copper ( cu ) or gold ( au ) on mineral or organic bases .\nsuch filters take advantage of the characteristic properties of the metals used in their production , i.e. , significant reflection coefficient for ir radiation and significant transmittance for the vis spectrum . despite the fact that the technique of deposition of interference layers has been known for many years the application of thin film ir filters in eye protections to block\nthe previous papers published by the authors of this study contain descriptions of the structure of interference filters designed for application in eye protections \nhighly effective in reduction of ir radiation with high level of transmission of the vis spectrum .\nthe authors investigated also the optical and mechanical parameters of the newly developed protective optic filters manufactured with the use of interference technologies .\nthe analysis of the results of the conducted tests demonstrated numerous advantages of interference technology application in the construction of protective filters , including : improved resistance to damage of the external protective filter surface ( cracking , scratching etc . ) as well as high reflection coefficients for the nir spectrum .\nthe aim of the present study was to compare the optic properties of protective filters manufactured by taking advantage of the interference technology and those coated with a single metallic layer reflecting ir radiation .\nthe coefficients characterizing their optic parameters , allowing to assess the protective properties within the vis and ir spectrum range were compared .\nthe following coefficients were analysed : \n luminous transmittance ( \n v),ir transmittance within the 7801400 nm range ( \n a),ir transmittance within the 7802000 nm range ( \n n),ir reflectance within the 7802000 nm range ( r \n n),ir absorptance within the 7802000 nm range ( a \n n),shade number ( n ) . \n \nluminous transmittance ( \n v ) , ir transmittance within the 7801400 nm range ( \n a ) , ir transmittance within the 7802000 nm range ( \n n ) , ir reflectance within the 7802000 nm range ( r \n n ) , ir absorptance within the 7802000 nm range ( a \n n ) , the level of protection ( shade number ) is determined on the basis of luminous transmittance ( the higher protection level correlates with the higher level of ir radiation blocked and appropriately lower vis light transmittance ) .\nprotection level consists of a code number ( e.g. , 4 ) for ir filters and a shade number ( e.g. , 3 , 5 , 7 ) calculated according to the following equation : \n ( 1 ) \n where \n v \n = luminous transmittance . for the particular level of protection , the mean ir transmittance within the 7801400 and 7802000 nm ranges as well as the ir reflectance and absorptance within the 7802000 nm range are determined .\nfor comparative analysis of the metallic reflective filters available in the market versus the interference filters developed by the authors , the following samples were prepared for the tests : \n off the shelf metallic reflective filters on a polycarbonate base ( flat parallel plate of 50 mm diameter and 2 mm thickness with a metallic layer of copper ( cu ) protection levels : 4 - 3 , 4 - 5 , 4 - 7);interference filters on a polycarbonate base ( flat parallel plate of 50 mm diameter with interference coating made up of the following materials : aluminium , h4 latio3 substance and silicon dioxide ) . \n off the shelf metallic reflective filters on a polycarbonate base ( flat parallel plate of 50 mm diameter and 2 mm thickness with a metallic layer of copper ( cu ) protection levels : 4 - 3 , 4 - 5 , 4 - 7 ) ; interference filters on a polycarbonate base ( flat parallel plate of 50 mm diameter with interference coating made up of the following materials : aluminium , h4 latio3 substance and silicon dioxide ) .\nthe protection levels , luminous transmittance and symbols used for marking the tested filters are presented in table 1 . \n\ncharacteristics of the filters.symbolluminous transmittance v ( % ) protection levelfilter typecu 4 - 314.1334 - 3metallic reflectiveitf 4 - 39.0824 - 3interferencecu 4 - 52.0214 - 5metallic reflectiveitf 4 - 51.4704 - 5interferencecu 4 - 70.3534 - 7metallic reflectiveitf\n4 - 70.1604 - 7interferencenote : protection level consists of code number ( 4 ) for infrared filters and shade number ( 3 , 5 , 7 ) calculated according to equation ( 1 ) . \n \nnote : protection level consists of code number ( 4 ) for infrared filters and shade number ( 3 , 5 , 7 ) calculated according to equation ( 1 ) .\noptical properties of the filters were measured with a cary 5000 spectrophotometer ( varian , australia ) . the spectrophotometer enabled transmittance or reflectance of optical radiation within the vis and nir spectrum to be recorded with 1 nm steps and 0.001% resolution level .\nspectral transmittance and reflectance measurements were carried out within the wavelength range of 7802000 nm .\nthe quartz halogen lamp was used as a source of radiation . to detect transmitted or reflected radiation\nthe photomultiplier tube and lead sulphide detector were used for vis and nir spectrum , respectively .\nspectral transmittance was measured with incident radiation falling normally on the filter surface in the visual centre ( defined as in ) . for spectral reflectance\nthe measurements were taken every second owing to the high absorption of investigated filters within the nir region .\nsince the minimum averaging time of the cary 5000 spectrophotometer was 0.0125 s , the values of transmittance or reflectance were measured 125 times for a given wavelength .\nthe aforementioned coefficients were calculated from the following equations [ 1012 ] : \n luminous transmittance \n ( 2 ) \n\n where ( ) = spectral transmittance , v( ) = spectral visibility function of the average human eye for daylight or night vision , s \n d65( ) = spectral energy distribution of standard illuminant d65 ; \n ir transmittance within the 7801400 nm range \n ( 3 ) \n\n where ( ) = spectral transmittance ; \n ir transmittance within the 7802000 nm range \n ( 4 ) \n\n where ( ) = spectral transmittance ; \n ir reflectance within the 7802000 nm range \n ( 5 ) \n\n where ( ) = spectral reflectance ; \n ir absorptance within the 7802000 nm range \n ( 6 ) \n\n where r \n n = ir reflectance within the 7802000 nm range , \n n = ir transmittance within the 7802000 nm range .\nluminous transmittance \n ( 2 ) \n ir transmittance within the 7801400 nm range \n ( 3 ) \n ir transmittance within the 7802000 nm range \n ( 4 ) \n ir reflectance within the 7802000 nm range \n ( 5 ) \n ir absorptance within the 7802000 nm range \n ( 6 ) \n the factor before integrals corresponding to the value of the measurement step at the measurement of spectral characteristics .\ntransmittance and reflectance characteristics of the studied filters.note : cu 4 - 3 = metallic reflective filter ; itf 4 - 3 = interference filter ; cu 4 - 5 = metallic reflective filter ; itf 4 - 5 = interference filter ; cu 4 - 7 = metallic reflective filter ; itf 4 - 7 = interference filter . \n \ntable 2 presents the values of coefficients determined on the basis of equations ( 3)(6 ) . \n\ninfrared transmittance within the 7801400 and 7802000 nm range , infrared reflectance within the 7802000 nm range and infrared absorptance within the 7802000 nm range . \ninfrared transmittance a and n ( % ) infrared reflectance rn ( % ) infrared absorptance an ( % ) symbola 7801400 ( nm)n 7802000 ( nm)rn 7802000 ( nm)an 7802000 ( nm)cu 4 - 31.4860.94283.51615.542itf 4 - 31.0030.56382.08417.353cu 4 - 50.2160.13487.31912.547itf 4 - 50.0380.00691.0378.957cu 4 - 70.0040.02388.30811.669itf 4 - 70.0040.03994.3125.649 \n\noptical radiation within the 7801400 nm spectrum range passes through the anterior compartment of the eye , the lens and reaches the retina . exposure to an excessive amount of radiation from this range\ncan result in burns of the retina and , in extreme cases , its permanent damage .\n, chronic long - term exposure may lead to the development of cataracts , referred to as ir or glass worker 's cataracts . in view of the above\nthe results presented on the graphs in figure 1 and the determined transmittance values ( see table 2 ) indicate unequivocally more effective blocking of ir radiation provided by interference filters .\nthe values of \n a and \n n for interference filters are lower even by an order of magnitude than those obtained for the metallic reflective filters .\nfor instance , the mean value of ir transmittance within the 7802000 nm range for interference filters with protection level 4 - 5 ( one of the most common protection levels used in the metallurgic industry ) equals 0.006% and is significantly lower than the maximum acceptable value specified in , which is 10.6% .\nfor all the investigated filters , the values of r \n n exceed 60% , which classifies them in the group of filters with increased ir reflectance .\nthe levels of the ir absorptance for metallic reflective filters and interference filters of 4 - 3 and 4 - 5 protection class are similar . for the highest of the investigated protection levels 4 - 7 \nthe above findings are important for selection of a filter appropriate for the radiation source .\nthe selection of filter protection level is dependent on the temperature of the radiation source .\nthe 4 - 7 level is used for radiation sources whose temperature exceeds 1600 k ( e.g. , occurs in the metallurgical industry ) . with such high temperatures ,\nreduction of filter heating as a result of exposure to ir radiation is important . as it follows from comparative analysis of the optic properties of filters taking advantage of the interference technology and filters coated with a single metallic layer reflecting ir radiation\n, the interference filters provide a more effective blocking of ir radiation in comparison with the currently used protective filters .", "answer": "the paper analyses the selected optical parameters of protective optic filters used for protection of the eyes against hazardous radiation within the visible ( vis ) and near infrared ( nir ) spectrum range . \n the indexes characterizing transmission and reflection of optic radiation incident on the filter are compared . \n as it follows from the completed analysis , the newly developed interference filters provide more effective blocking of infrared radiation in comparison with the currently used protective filters .", "id": 320} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute cytomegalovirus ( cmv ) infection is common in both immunocompromised and immunocompetent patients worldwide.12 the infection is often asymptomatic .\nsymptoms , when they occur , include fever , cervical lymphadenitis , and arthralgia.3 rarely , acute cmv infection may be complicated by pneumonia , colitis , myocarditis , pericarditis , or hemolytic anemia.4 vascular events caused by acute cmv infection , including thrombosis of the venous or arterial vascular system , are rarely reported in the english literature .\nwe report a case of acute cmv colitis in an immunocompetent adult that was complicated by vascular thrombosis and pulmonary embolism .\nfurther , we present a review of the literature regarding the association between vascular events and cmv infection in immunocompetent patients .\na 78-year - old man was referred to our emergency department with a 3-day history of diarrhea and fever .\nhe had no recent travel history , did not use steroids , and had not experienced recent trauma .\nhe used medication for hypertension and diabetes mellitus , both of which were well controlled . on admission ,\nhis vital signs were : body temperature , 38.8 ; blood pressure , 145/85 mmhg ; respiratory rate , 18/min ; and pulse rate , 90/min . on physical examination , his pulse was regular and he had no cardiac murmurs , his chest was clear without signs of respiratory distress , and his abdomen was soft with hyperactive bowel sounds .\nlaboratory tests showed a white blood cell count of 8,270/mm ( normal : 3,99010,500/mm ) , a platelet count of 199,000/mm ( normal : 140,000450,000/mm ) , a prothrombin time of 14.10 seconds ( control : 11.16 seconds ) , an inr of 1.21 , an activated partial thromboplastin time of 26.0 seconds ( control : 27.4 seconds ) , and crp level of 16.7 mg / dl ( normal : < 0.8 mg / dl ) . a coagulation profile , including protein c ( 80% , normal : 70%140% ) , protein s ( 75% , normal : 60%130% ) and anti - thrombin iii ( 95% , normal : 75%125% ) , was normal .\n. colonoscopy demonstrated multiple giant ulcers with skip lesions in the distal colon , sparing the rectum ( fig .\nmultiple forceps - biopsy tissue samples , taken from the coloniculcers , were sent for pathological examination .\nhowever , 5 days post - colonoscopy , the patient experienced dyspnea and severe hypoxemia , necessitating emergent endotracheal intubation and ventilation .\na chest radiograph obtained post - intubation revealed an engorged main pulmonary trunk with an abrupt cutoff of pulmonary vascularity in the distal portions bilaterally , indicative of the \" westermark sign \" ( fig .\nsubsequently , a ct scan of the chest was performed that showed several filling defects within the pulmonary trunk and main pulmonary arteries ( fig .\nhistological evaluation of the colonic biopsy specimens revealed cytomegalic cells with densely staining nuclei and intranuclear inclusion bodies in the epithelium ( fig .\nthese epithelial cells were positive for monoclonal anti - cmv antibody on immunohistochemical analysis , indicative of cmv infection ( fig .\nthe patient had no obvious risk factors for thrombosis , and had no family history of coagulopathy .\nfollow - up ct scan of the patient 's chest showed complete resolution of the pulmonary emboli .\nacute cmv infection in immunocompetent patients is common worldwide , with seroprevalence rates ranging from 40% to 100% , depending on country , socio - economic conditions , and age.1 colitis is the most common manifestation of severe cmv infection.2 patients with cmv colitis are generally asymptomatic ; if symptomatic , they may present with diarrhea , fever , bleeding , abdominal pain , and perforation .\n4 vascular events are a very rare manifestation of severe cmv infection in immunocompetent individuals.2 these vascular events include thrombosis of the portal , superior mesenteric , or splenic vein ; cerebral venous thrombosis ; deep vein thrombosis ; and life - threatening pulmonary embolism .\n567 vascular complications may be discovered only several weeks after the initial diagnosis of cmv infection . however , abgueguen et al . proposed that venous thrombosis in immunocompetent patients with cmv infection may not be as rare as previously reported.8 although the pathogenesis of cmv - induced vascular events is unknown ,\nseveral mechanisms have been postulated , including direct damage to endothelial cells , increased levels of hemostatic indicators , induction of smooth muscle proliferation , enhanced platelet - derived growth factor production , and the presence of antiphospholipid antibodies.91011 vascular thrombosis in immunocompetent patients is usually associated with predisposing factors such as heterozygous factor v leiden mutation , presence of antiphospholipid antibodies , heterozygous prothrombin gene mutation , protein c and/or protein s deficiency , or oral contraceptive use.12 in contrast , this patient had no family history of coagulopathy , was not bed - ridden , and had no other risk - factors for thrombosis .\nit is , therefore , likely that cmv infection was the precipitating factor for pulmonary embolism . in the diagnosis of vascular events caused by cmv infection ,\ndoppler ultrasound and ct scanning are the most useful diagnostic modalities.6 treatment of cmv - associated pulmonary embolism includes immediate administration of antiviral agents and anticoagulants .\nadvanced age , male gender , presence of immune - modulating comorbidities , and need for surgical intervention all negatively influence survival.13 although the cost - effectiveness of investigating for acute cmv infection in patients presenting with thrombosis has not yet been established , we believe that serum samples for cmv infection should be obtained and endoscopic examination should be considered in patients with idiopathic thrombosis . in conclusion , although pulmonary embolism caused by acute cmv colitis in immunocompetent patients is extremely rare , it should be considered in patients who present with severe respiratory symptoms . to the best of our knowledge ,\nthis is the first report of an immunocompetent patient with acute cmv colitis complicated by vascular thrombosis with pulmonary embolism in which no other obvious underlying predisposing factor for thrombosis was identified .", "answer": "acute cytomegalovirus ( cmv ) infection occurs commonly in immunocompromised and immunocompetent patients , but is usually asymptomatic in the latter . \n vascular events associated with acute cmv infection have been described , but are rare . \n hence , such events are rarely reported in the literature . \n we report a case of pulmonary embolism secondary to acute cmv colitis in an immunocompetent 78-year - old man . \n the patient presented with fever and diarrhea . \n colonic ulcers were diagnosed based on colonoscopy findings , and cmv was the proven etiology on pathological examination . \n the patient subsequently experienced acute respiratory failure . \n pulmonary embolism was diagnosed based on the chest radiography and computed tomography findings . \n a diagnosis of acute cmv colitis complicated by pulmonary embolism was made . \n the patient was successfully treated with intravenous administration of unfractionated heparin and intravenous ganciclovir .", "id": 321} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nGold Catalyzed Decarboxylative Cross-Coupling of Iodoarenes\n\nPaper sections:\n\nGold was once thought to have few uses in fine chemical synthesis. 1 Advances in homogeneous gold catalysis demonstrated that gold(I) complexes can promote a wide variety of synthetically relevant transformations. [2][3][4][5] Most employ a gold(I) catalyst as a Lewis acid or \u03c0-activator, where gold is thought to formally remain at the +1 oxidation state. The apparent redox stability of gold(I) complexes [6][7][8] contrasts with prominent two electron redox events known for palladium, rhodium, platinum, and iridium complexes. The redox stability of gold(I) complexes has limited development of complementary methods utilizing redox gold catalysts. This work describes a gold catalyzed decarboxylative cross-coupling reaction.
Pioneering studies demonstrated that gold(I) complexes could participate in oxidative addition with methyl iodide, 9,10 trifluoromethyl iodide, 11,12 aryl diazonium salts, [13][14][15][16][17][18] iodine(III) reagents, [19][20][21][22][23][24][25][26] and other strong oxidants. [27][28][29] Initially Lloyd-Jones and co-workers demonstrated a catalytic oxidative coupling of aryl silanes in the presence of a strong acid and a stoichiometric iodine(III) oxidant (Scheme 1a). 20,21 A limiting feature of this and subsequent work [22][23][24][25][26]30,31 is that the site selectivity of C-H bond activation is governed by an apparent electrophilic aromatic substitution (EAS) mechanism. Patil and coworkers demonstrated a dual gold/photoredox catalyzed cross-coupling with aryl silanes 17 or aryl stannanes, which is thought to occur via a radical mechanism (Scheme 1b). 18 The direct oxidative addition with more standard and less hazardous aryl halide electrophiles (e.g. Ar-I), which is standard for palladium(0), is relatively rare with gold(I). 6,7,[30][31][32][33][34][35][36][37][38] The barrier for the oxidative addition of gold(I) complexes into aryl halides can be decreased through the use of bidentate ligands with a hemilabile site. 6,33,37 Amgoune, Bourissou, and co-workers recently disclosed a gold catalyzed arylation of electron rich indoles and trimethoxybenzene with aryl halides (Scheme 1c). 30,31 This was recently expanded to amination. 38,39 Attempts at expanding this reactivity to more common organometallic reagents have been problematic. In an elegant study, Bower, Russell, and co-workers demonstrated that all three elementary steps in a putative gold(I/III) cross-coupling are viable. 6,32 However, this reactivity was not incorporated into a catalytic method. Additionally, aryl boron reagents were found to be sub-optimal coupling partners, which may be due to a challenging and potentially endothermic transmetalation. 40,41 An alternative to transmetalation would be to utilize decarboxylation.
\n\nScheme 1. Gold Catalyzed Biaryl Formations\nOur lab has focused on decarboxylative cross-coupling. 42,43 Decarboxylative functionalization reactions are recognized as promising alternatives to traditional cross-couplings because expensive or unstable organometallic reagents can be replaced by readily available benzoic acids . [44][45][46][47][48] Inspired by two reports describing stoichiometric gold(I) mediated decarboxylation, 49,50 we surmised that this elementary step could offer an alternate pathway to gold-aryl complexes, obviating traditional transmetalation. 6,40,41 Presented herein is a gold catalyzed decarboxylative cross-coupling reaction between iodoarenes and (hetero)aryl carboxylates (Scheme 1e). This work represents the first site-specific gold catalyzed cross-coupling with standard coupling partners and the first gold catalyzed decarboxylative coupling of (hetero)aryl carboxylates. Initial trials were inspired by Amgoune and Bourissou, who recommended MeDalphos as a ligand. 30,31 The use of sodium carboxylate 1a (M = Na) with NaOTf did not produce any detectible biaryl (Table 1, entry 1). Excitingly, using AgOTf afforded cross-coupled product 3a along with protodecarboxylation product 4 (entry 2). 51 Switching from a sodium carboxylate to a silver carboxylate (entry 3) and decreasing the loading of AgOTf dramatically improved the yield (entry 4). Changing the limiting reagent to iodoarene 2a significantly diminished the yield (entry 5).
\n\nTable 1. Optimization for Gold Catalyzed Decarboxylative Cross-Coupling\na Reactions conducted with benzoate 1a (0.1 mmol), iodoarene 2a (0.5-1.0 mmol), in 1,2-dichlorobenzene (0.5 M, DCB), with 5 mol % [Au]. b Yield determined by 19 F NMR analysis. All yields reflect the average of duplicate trials. c Reactions conducted neat in iodoarene 2a. d A variety of precatalysts were screened and it was discovered that Buchwald style phosphine ligands performed well under neat conditions (entries 6-11). 52 The quantity of iodoarene was decreased from 10 equiv to 5 equiv (entries 12-13). The t BuXPhos ligand outperformed the t BuJohnphos ligand under these conditions. Next, the counterion on the precatalyst was evaluated (entries 14-16). With LAuCl or LAuI complexes, in the absence of silver trifluoromethanesulfonate, significant homocoupling of benzoate 1a was observed. The optimal precatalyst was LAuNTf2 (entry 17). A further reduction in the iodoarene to 3 equiv was tolerated but decreased the selectivity (entry 18). The reaction was conducted in a new vial with a new stir bar to avoid possible contamination, 53 which did not significantly affect the yield (entry 19). In the absence of gold, small amounts of product were observed along with significant protodecarboxylation (entry 20, see SI for additional trials and control experiments).
The substrate scope of the iodoarene was investigated (Table 2). Substrate 3a was isolated in excellent yield (86%). Iodobenzene (3b), 4-iodoanisole (3c), and 4-iodobenzotrifluoride (3d) afforded product, covering the traditional Hammett series (4-OMe, \u03c3p = -0.27; 4-CF3, \u03c3p = 0.54). Iodoanisole gave an improved yield at 120 \u00b0C, while iodobenzotrifluoride required heating to 160 \u00b0C. This matches prior observations demonstrating that oxidative addition at gold(I) is faster with electron rich substrates (vide infra). 31,33 Iodoarenes with meta substituents gave acceptable yields (3e-3h). The reaction tolerated ortho groups (3i-3k). Chemoselectivity was observed for oxidative addition in the presence of aryl chlorides (3j) and aryl bromides (3h, 3k). Iodonaphthalene (3l) also worked well.
\n\nTable 2. Substrate Scope of Iodoarene\nYield determined by 19 F NMR. Yield in parenthesis is the isolated yield. All values are the average of duplicate reactions. Reaction conducted at a 120 \u00b0C, b 160 \u00b0C, c in 1,2-dichlorobenzene. See SI.
A competition experiment was conducted between 4-iodoanisole (2c) and 4-iodobenzotrifluoride (2d, Table 2 bottom). The reaction afforded biaryl 3c as the major product with a 3c:3d ratio of 3.3:1. A similar competition experiment with stoichiometric MeDalphosAuSbF6, afforded gold(III) complexes with a ratio of 6.7:1. 31 The inversion of reactivity, relative to oxidative addition at palladium(0), 54 is a potential hallmark of gold oxidative addition. 27,31,33 The substrate scope with respect to the aryl carboxylate was investigated (Table 3). It is well recognized in the area of palladium, copper, and silver decarboxylative cross-coupling that substrates with polarizing ortho substituents are particularly reactive. [44][45][46][47][48] Hoover and co-workers correlated the field effect parameter (Fortho) to reactivity for silver mediated protodecarboxylation. 55 Here, products 3m -3v could be isolated in good to excellent yield and these results qualitatively correlate to the field effect parameter. Less activated substrates required elevated temperatures and/or increased catalyst loading (3v -3y). It is particularly exciting that substrates 3x and 3y can be isolated in any yield given the scope limitations of other decarboxylative cross-coupling reactions. 43,48,56 Substrates with an ortho C-H bond did not afford product with palladium catalyzed reactions 42,43,56 and a chlorine substituent (3y) is not considered to be particularly polarizing. A substrate with an orthomethoxy was not activated enough to provide an acceptable yield (3z, Fortho = 0.29). Activated pyridine carboxylates afforded products 3aa and 3bb. Pyridines are particularly challenging substrates in traditional cross-coupling reactions. [57][58][59] It is conceivable that the observed cross-coupling reaction could proceed via protodecarboxylation 51,55 and subsequent C-H bond activation. 60 This concern is valid because product 4 was observed and since carboxylates facilitate C-H bond activation. 60 A reaction with 1,3-difluorobenzene (4) and excess silver benzoate 1o afforded a negligible quantity of product 3a (Scheme 2a). The majority of compound 4 was detected after the reaction, with the mass loss being attributed to volatility. As such, a protodecarboxylation and C-H bond activation sequence is unlikely.
\n\nTable 3. Substrate Scope of (hetero)aryl carboxylates\nYield determined by 19 F NMR. Yield in parenthesis is the isolated yield. All values are the average of duplicate reactions. Reaction conducted a in 1,2-dichlorobenzene at 0.1 M, b in 1,2-dichlorobenzene at 0.17 M, c at 180 \u00b0C, d at 180 \u00b0C using 10 mol % [Au]. See SI. Fortho = field effect parameter.
A tentative mechanism was supported by monitoring various elementary steps with isolated complexes (Scheme 2). Benzoate 1a' underwent salt metathesis, yielding complex Au1 (Scheme 2b). Gold(I)-aryl complex Au2 could be isolated via thermolysis of complex Au1 (Au2 crustal structure shown, Scheme 2b), indicating that gold mediated decarboxylation is viable. 49,50 Heating complex Au2 in neat iodoarene provided some biaryl (Scheme 2c). The majority of complex Au2 remained unreacted, even after 24 h. However, when AgOTf was used with complex Au2, product 3a was observed in high yield (Scheme 2c). This suggests that silver is needed to either promote oxidative addition or reductive elimination en route to product 3a. Tetracoordinate gold(III) complexes can be stable and halide abstraction can trigger reductive elimination. 12,27 While minimal product 3a was formed from complex Au2 (Scheme 2c) in the absence of silver, using stoichiometric t BuXPhosAuNTf2 with carboxylate 1a' did produce product 3a (21%) as well as complex Au2 (36%, Scheme 2d). Potentially, t BuXPhosAuNTf2 can abstract iodide from a putative gold(III) complex, while complex Au2 does not. To test this hypothesis, complex Au2 was subjected to the reaction conditions with added t BuXPhosAuNTf2 (Scheme 2e) and product 3a was observed. These results demonstrate that silver is not required and the most likely role for AgOTf is to promote halogen abstraction prior to reductive elimination from an Au(III) complex. 12,27 A reversible and endothermic oxidative addition is also possible and would complicate the isolation of Au(III) complex. In conclusion, we report the first gold catalyzed decarboxylative cross-coupling. This work expands on recent progress regarding gold(I) oxidative addition. Decarboxylation overcomes site selectivity limitations associated with prior gold catalyzed arylations. The scope of the aryl carboxylate correlates qualitatively with the field effect parameter and preliminary studies indicate that all steps in a catalytic cycle can occur at gold. A more comprehensive mechanistic study will be reported in due course.
", "answer": "This report details a decarboxylative cross-coupling of (hetero)aryl carboxylates with iodoarenes in the presence of a gold catalyst (>25 examples, up to 96% yield). Generating an aryl nucleophile via decarboxylation obviates problems associated with transmetalation at a putative gold(III) complex. This reaction is site specific, which overcomes prior limitations associated with gold catalyzed oxidative coupling reactions. The reactivity of the (hetero)aryl carboxylate correlates qualitatively to the field effect parameter (Fortho). Furthermore, each step in a proposed mechanism was observed from isolated gold complexes, supporting a gold catalyzed mechanism.", "id": 322} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfor many patients with multivessel disease , pci is a definitive alternative to coronary artery by - pass graft ( cabg ) [ 1 , 2 ] .\ncomplete revascularization remains a desirable goal , and a satisfactory outcome may be obtained with complete revascularization with ptca or cabg [ 4 , 5 ] .\nhowever , complete revascularization may not be possible in many patients , either because of the operator inability to treat all diseased coronary arteries such as chronic total occlusions and adverse stenosis morphology or simply being not easy to plan in the presence of coronary narrowing less than severe ( > 50% but < 70% ) .\nalternatively , the operator might decide to selectively revascularize only large areas of myocardium at risk .\nindeed , clinical reasons for this decision include , among others , unstable angina , recent myocardial infarction , severe left ventricular dysfunction , urgent / emergent pci , preexisting renal failure for which the amount of angiographic contrast media should be limited , and premature termination of the procedure for unexpected problems , such as in those elderly or frail patients who can not lay flat for prolonged periods .\nthus , revascularization of the culprit lesion may be part of an incomplete revascularization strategy which may be of value other than a common clinical practice in many selected cases , when wisely chosen because of its easier achievement and lower immediate risk .\nin the bari trial comparing cabg with multivessel pci , the 10-year survival did not differ between the two treatments despite the fact that 91% of significant lesions were bypassed in the cabg patients compared to 54% of significant lesions in the pci patients . in the same trial , cardiac death ,\nmyocardial infarction and angina at 10-year follow - up were similar in patients in whom a pci was performed as a planned incomplete revascularization , as compared to those with a planned complete revascularization .\nfurthermore , even in patients for whom complete revascularization with angioplasty was planned , only 50% of lesions were both attempted and dilated .\nsimilar results were obtained by vandormael et al . who found an important symptomatic relief achieved with partial revascularization in patients with multivessel disease .\nin these patients , 1-year cardiac event rate was not significantly higher than the rate in the group with complete revascularization . at followup ,\n66% of patients with complete revascularization were asymptomatic and 84% had clinical improvement ; this was similar to 58% and 85% , respectively , for patients with incomplete revascularization .\nthus , incomplete revascularization seems to be a valuable solution when a culprit lesion can be identified , particularly when this vessel is a favourable lesion which serves a large noninfarct territory , or in case of an acute coronary syndrome where there is the need to stabilize patient 's condition [ 11 , 12 ] .\nmoreover , in the arterial revascularization therapies studies ( arts ) , randomization of stenting in patients with incomplete revascularization including diabetics did not influence late mortality . \nhowever , in multivessel disease , complete revascularization is often an achievable goal not often pursued both by pci and cabg , despite the fact that the latter is generally more complete . indeed , even when complete revascularization is planned such as in the chronic total occlusion subgroup of the syntax trial , complete revascularization is obtained in only 49.4% of pci treated patients while in only 68.1% of cabg treated patients .\nmore recently , in the five - year outcome of the arts ii study , there was no significant difference in survival rates between patients with complete and incomplete revascularization treated by pci or cabg .\nconversely , this study showed a significantly lower free - from - mace survival in patients with higher syntax tertiles compared to the lower and intermediate ones .\n\n exercise testing is a widely used method particularly valuable in assessing cardiovascular status after the occurrence of a cardiac event or therapeutic interventions such as pci .\nwhen it is performed after discharge it is helpful for activity counseling and/or exercise training as part of the cardiac rehabilitation program .\nhowever , data obtained from two meta - analyses demonstrate that exercise testing , even if information from the electrocardiogram and symptomatic data is synthesized , is poor diagnostic for myocardial ischemia with a sensitivity of 46% and a specificity of 77% [ 6 , 7 ] .\nthe use of stress nuclear imaging increases significantly the sensitivity to 87% and the specificity to 78% , while that of stress echocardiography imaging increases the sensitivity to 63% and the specificity to 87% .\nthe lower sensitivity of the exercise ecg compared to imaging techniques in clinical practice is worsened further by inadequate stress yielding low exercise heart rates , the use of drugs that are known to influence test results , and the extent of disease in vessels other than those dilated .\nfurthermore , the exercise electrocardiogram does not permit the determination of location of the ischemia , nor does it accurately assess the extent of ischemia ; these factors are often crucial in the clinical decision making after - pci . \nalthough exercise testing has the advantage of widespread availability and relatively low cost , the higher test accuracy obtained by stress imaging provides greater advantages for clinical assessment of these patients .\nan additional advantage is that pharmacological imaging stress testing may be performed in patients who are unable to exercise or who have an uninterpretable electrocardiogram .\nseveral studies [ 6 , 7 , 1623 ] employing spect myocardial perfusion imaging ( mpi ) at different times from pci have shown high level of sensitivity and specificity of nuclear imaging when compared to those of coronary angiography ( figures 1 and 2 ) .\nthe overall performance of spect - mpi for the detection of myocardial ischemia was 79% for both sensitivity and specificity .\nthe decreased specificity observed when mpi is performed prematurely after pci was initially noted following ptca [ 2426 ] and after coronary stenting [ 27 , 28 ] .\nindeed , mpi may be altered as a consequence of impaired flow reserve due to an epicardial coronary stenosis or , in the absence of coronary obstruction , as a consequence of an endothelial dysfunction and medial injury at the treated site or abnormal microvascular and resistive vessel function distal to the pci site as shown by various authors [ 29 , 30 ] and by us in two editorials [ 31 , 32 ] . \nsimilar to mpi , echocardiography in conjunction with exercise provides useful functional assessment of coronary lesions and has a high concordance with myocardial scintigraphy .\nmertes and colleagues found that exercise echocardiography may predict the development of recurrent ischemia after ptca , with a sensitivity of 83% and specificity of 85% .\nthe functional significance of a lesion may also be determined with the use of pharmacological stress .\nfor the detection of coronary restenosis , exercise , dipyridamole , and dobutamine echocardiography have shown a diagnostic accuracy similar to that seen with mpi although a lower sensitivity ( 75% to 87% ) and a slight higher specificity ( 84% to 95% ) were found in the direct comparison with the nuclear data [ 36 , 37 ] .\na limitation of stress echocardiography is the inability to get acceptable quality images of left ventricle walls in about 15% of patients .\nindeed , if this exam is performed at institutions and interpreted by physicians with adequate experience and training , it is considered of major importance for coronary artery disease detection and , along with gadolinium , for viability detection to predict left ventricular function recovery .\nboth mpi and stress echocardiography have a clear superiority with regard to specificity and predictive value for postrevascularization events [ 4044 ] .\nindeed , for mpi , these findings have been shown regardless of the method selected and include the use of 201tl or 99mtc radiopharmaceuticals or after the use of different modes of stress imaging [ 4548 ] . in the angioplasty\ncompared to medicine study , 328 patients were randomized to ptca or to medical therapy . at six months after randomization\n, 82% of patients underwent stress mpi and were followed for more than five years .\nmortality in the ptca group was 20% for those with a reversible defect versus 7% for those without such a defect ( p = 0.03 ) . by multivariate analysis , the strongest predictors of mortality were diabetes , smoking , and a reversible perfusion defect at mpi .\nsimilarly , the relative prognostic information derived from mpi at 1 year after revascularization for patients with multivessel coronary artery disease included in the prospective east trial reveals a strong correlation between detected ischemia on thallium scintigraphy and subsequent events [ 45 , 47 ] .\nmore recently , in patients with incomplete revascularization procedures , we demonstrated that exercise spect mpi provides significant independent information concerning the subsequent risk of both hard and soft cardiac events , with a composite annualized event rate < 2% for patients with a normal scan ( figure 3 ) .\nmpi is able to provide incremental prognostic information after adjusting for clinical , angiographic , and exercise variables and is able to predict the occurrence of cardiac hard and soft events when separating patients according to the presence of myocardial ischemia and necrosis ( figures 4 and 5 ) .\nthe results of this study suggest that certain high - risk patients , such as those with multivessel coronary artery disease , treated by incomplete revascularization may benefit from routine mpi ; this is especially true for low - risk patients as shown by ho and colleagues who studied 211 patients between 1 and 3 years after pci and monitored them for 7.3 years . despite a low overall annual event rate of 1% per year ,\nan abnormal mpi was significantly predictive of cardiac death or mi , whereas a normal mpi was associated with low risk .\nto date , the major evidence that supports revascularization in patients with an abnormal mpi is based on the following three studies .\nexamined a prospective database from a single center and classified patients on the basis of the severity of ischemia on stress mpi and examined the effect of revascularization versus medical therapy on subsequent mortality after an average followup of two years .\nthere was no difference in mortality between medical therapy and revascularization in patients with ischemia < 10% of myocardium , while patients with an ischemia > 10% had lower mortality with revascularization .\nthese results were also confirmed in the nuclear substudy of the courage trial , in which patients with stable angina had paired mpi studies performed at baseline and 618 months after randomization of optimal medical therapy versus optimal medical therapy and pci .\na reduction of ischemia > 5% on mpi was associated with a 13.4% rate of the death / myocardial infarction composite event rate , whereas in those with no reduction of ischemia the composite event rate was 27.4% ( more than two - fold ) . indeed , pci was more effective in achieving an ischemia reduction of > 5% compared to medical therapy ( 33% versus 19.8% , p = 0.004 ) .\nthese two studies suggest that the benefits of revascularization over medical therapy are related rather than to a more complete anatomical revascularization , to a significant reduction of ischemia , revascularization driven .\nsimilarly , in a recent study by our group in patients with a residual cto in a main coronary artery left untreated after pci who underwent follow - up stress mpi , myocardial perfusion imaging provided significant independent information concerning the subsequent risk of cardiac events .\nindeed , patients with severe ischemia had significantly higher rates of death and myocardial infarction than those with either mild ischemia or no ischemia .\nfurthermore , by characterizing the type of defect in terms of presence of scar , ischemia only , or scar and ischemia , we observed that patients with ischemia had the worst outcomes .\nthis study emphasizes the prognostic significance of ischemia on stress mpi even in patients with chronically occluded coronary vessels , so refocusing the attention on the difference between anatomic and functional revascularization .\nthis study , with all others from literature , underlines that it is not the anatomic severity of coronary disease which determines prognosis , rather the achievement of a functionally complete revascularization , in other words revascularization of all coronary arteries which serve only ischemic and viable myocardial segments [ 9 , 13 , 52 , 53 ] ( figure 6 ) .\nthis is why many studies evaluating the impact of completeness of revascularization strategy based only on anatomic criteria ( coronary stenosis 50% ) have failed to demonstrate improvements in survival rates .\nalthough complete revascularization remains a desirable goal in multivessel disease patients , incomplete revascularization strategy may be a preferred treatment strategy and a common clinical practice in many selected cases , when wisely chosen , because of its easier achievement and lower immediate risk . among these incompletely revascularized patients , mpi is able to identify those patients with ischemic and viable myocardial regions , in which a functionally complete revascularization is needed to improve their outcome ( figure 7 ) .", "answer": "percutaneous coronary intervention ( pci ) is actually the most used method of revascularization . \n although complete revascularization remains a desirable goal , it may not be possible or not easy to plan in many patients . \n thus , incomplete revascularization might be a preferred treatment strategy in selected patient categories . \n stress myocardial scintigraphy , because of its high diagnostic accuracy and prognostic value and its ability to assess location and extent of myocardial ischemia regardless of symptoms as well as to evaluate patients who are unable to exercise or who have uninterpretable electrocardiogram , is of paramount importance for clinical decision making in patients with multivessel disease and incomplete revascularization .", "id": 323} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napproximately 225,000 primary total hip arthroplasties ( thas ) are performed in the united states per year , and projections indicate that more than 4 million thas will be performed annually by 2030.1 neurologic injury after tha is reported to occur in 0.09 to 3.7% of primary thas and 0 to 7.4% of revision thas.2 noted causes of neurologic injury include direct intraoperative nerve injury , leg lengthening , excess retraction , cement extravasation , cement - related thermal damage , patient positioning , and postoperative hematoma.2 the majority of these injuries are symptomatic within the early postoperative period and can be managed conservatively with close follow - up . delayed onset of neurologic injury\nwe report a case of neuropathy caused by malposition of an acetabular cup screw causing direct injury to the sciatic nerve .\nthe patient developed progressively worsening loss of ankle dorsiflexion , resulting in complete footdrop 2 years after initial tha .\nthe presentation , intervention , and outcome of other cases of delayed neuropathy are reviewed in the present report .\ndelayed neuropathies are most often caused by irritation from hardware , component failure , or wear - related pseudotumors .\nthe patient was a 52-year - old woman with end - stage arthritis of her bilateral hips with previous uncomplicated right tha that underwent an elective left tha .\nno intraoperative complications , abnormal anatomic landmarks , or events were noted at the time of surgery .\nthe patient 's initial orthopedic postoperative course was complicated by paresthesias of the right lower extremity , severe hypesthetic pain primarily in the lateral and anterior aspect of the right calf , and severe sciatica . during her hospital\nstay , the patient 's sensation and pain improved ; however , less than 1 year after her tha she noted gradual onset of weakness in her right lower extremity .\n, she had developed a complete footdrop with loss of ankle dorsiflexion and required the use of an ankle - foot orthosis ( afo ) to ambulate .\nshe underwent an emg at an outside facility , had a neurologic evaluation , and was undergoing physical therapy .\nthe patient had 0/5 dorsiflexion strength with 3/5 eversion and 5/5 inversion and plantarflexion strength .\ndecreased sensation was noted in the lateral aspect of the leg and the dorsum of the foot .\nshe had no gross deformity of the lower extremity and had normal quadriceps and hamstring strength at the knee and the hip .\nemg showed severely reduced amplitude of the peroneal compound muscle action potentials and unrecordable superficial peroneal sensory response .\nfibrillation potentials were seen in the peroneal division of the sciatic nerve with minimal evidence of reinnervation changes to the muscle units .\nthis localized the lesion to proximal to the short head of the bicep femoris muscle .\nthis led to obtaining advanced imaging consisting of a computed tomography ( ct ) of the pelvis , which demonstrated a malpositioned acetabular cup screw within the soft tissues adjacent to the sciatic nerve ( fig .\nthe sciatic nerve was dissected via internal neurolysis into peroneal and tibial divisions at the level of the buttock .\nthe division of the sciatic complex was dissected proximally to the exit of the sciatic from the pelvis .\nthe peroneal portion of the nerve was found to be compromised by the malpositioned screw .\nthere was no neuroma identified at the site of nerve compression , although there was evidence of nerve displacement by the protruding screw .\nthe nerve was stimulated locally and nerve action potentials were recorded proximal and distal to the site of injury .\nboth peroneal and tibial portions of the nerve were tested separately to avoid false - positive conduction from the tibial division .\nthe intraoperative recordings showed preservation of conduction across the site of nerve impingement ( fig .\nthe nerve was reflected off the head of the screw and gently moved proximally toward the sciatic notch .\nwhen the nerve was free of the screw and protected , a titanium cutting drill bit was used to shorten the screw so that it was flush with the bony interface . repeated\nstimulation of the nerve confirmed that action potentials were still able to propagate past the site of injury .\nthe patient is now 2 years out of surgery and has demonstrated some recovery of peroneal nerve function , supporting the decision to pursue external neurolysis . the patient 's improvement has not been complete and the patient requires an external orthosis .\nthe patient was a 52-year - old woman with end - stage arthritis of her bilateral hips with previous uncomplicated right tha that underwent an elective left tha .\nno intraoperative complications , abnormal anatomic landmarks , or events were noted at the time of surgery .\nthe patient 's initial orthopedic postoperative course was complicated by paresthesias of the right lower extremity , severe hypesthetic pain primarily in the lateral and anterior aspect of the right calf , and severe sciatica . during her hospital\nstay , the patient 's sensation and pain improved ; however , less than 1 year after her tha she noted gradual onset of weakness in her right lower extremity .\n, she had developed a complete footdrop with loss of ankle dorsiflexion and required the use of an ankle - foot orthosis ( afo ) to ambulate .\nshe underwent an emg at an outside facility , had a neurologic evaluation , and was undergoing physical therapy .\nthe patient had 0/5 dorsiflexion strength with 3/5 eversion and 5/5 inversion and plantarflexion strength .\ndecreased sensation was noted in the lateral aspect of the leg and the dorsum of the foot .\nshe had no gross deformity of the lower extremity and had normal quadriceps and hamstring strength at the knee and the hip .\nemg showed severely reduced amplitude of the peroneal compound muscle action potentials and unrecordable superficial peroneal sensory response .\nfibrillation potentials were seen in the peroneal division of the sciatic nerve with minimal evidence of reinnervation changes to the muscle units .\nthis localized the lesion to proximal to the short head of the bicep femoris muscle .\nthis led to obtaining advanced imaging consisting of a computed tomography ( ct ) of the pelvis , which demonstrated a malpositioned acetabular cup screw within the soft tissues adjacent to the sciatic nerve ( fig .\nthe sciatic nerve was dissected via internal neurolysis into peroneal and tibial divisions at the level of the buttock .\nthe division of the sciatic complex was dissected proximally to the exit of the sciatic from the pelvis .\nthe peroneal portion of the nerve was found to be compromised by the malpositioned screw .\nthere was no neuroma identified at the site of nerve compression , although there was evidence of nerve displacement by the protruding screw .\nthe nerve was stimulated locally and nerve action potentials were recorded proximal and distal to the site of injury .\nboth peroneal and tibial portions of the nerve were tested separately to avoid false - positive conduction from the tibial division .\nthe intraoperative recordings showed preservation of conduction across the site of nerve impingement ( fig .\nthe nerve was reflected off the head of the screw and gently moved proximally toward the sciatic notch .\nwhen the nerve was free of the screw and protected , a titanium cutting drill bit was used to shorten the screw so that it was flush with the bony interface . repeated\nstimulation of the nerve confirmed that action potentials were still able to propagate past the site of injury .\nthe patient is now 2 years out of surgery and has demonstrated some recovery of peroneal nerve function , supporting the decision to pursue external neurolysis .\nthe patient 's improvement has not been complete and the patient requires an external orthosis .\ntha is a widely used procedure for the treatment of end - stage hip arthritis that is able to restore functional ability to hundreds of thousands of patients a year in the united states .\nthere is a known risk of immediate neuropathy from mechanisms such as intraoperative compression from retractors , hematoma , limb lengthening , and inappropriate patient positioning .\nhowever , there is also a rarer risk of delayed neuropathy after tha that has different causative pathologies .\nour findings from the literature suggest that late complications from tha may be more likely due to migration of hardware over time with subsequent nerve compression or reactive mass or fluid collection . in our case , a long , malpositioned screw was found in the soft tissue compressing the peroneal branch of the sciatic nerve .\na search of the pubmed database was conducted using the search term delayed neuropathy after total hip arthroplasty covering the years 1950 through 2015 .\nfifteen case reports on 16 patients were selected based on involvement of a neuropathy that appeared after tha.3 \n 4 \n 5 \n 6 \n 7 \n 8 \n 9 \n 10 \n 11 \n 12 \n patients presenting prior to 1 month included those that developed postoperative hematomas , had poor patient positioning , had previously undiagnosed hereditary neuropathy with liability to pressure palsies ( hnpps ) , or had anesthetic - induced inflammatory neuropathy and were felt to qualify as early postoperative complications .\ndelayed onset was defined as those with neuropathies developing over 1 month from surgery .\nabbreviations : afo , ankle - foot orthosis ; ct , computed tomography ; emg , electromyography ; ir , interventional radiology ; mri , magnetic resonance imaging ; tha , total hip arthroplasty .\ndate of presentation ranged from 4 months to 9 years postoperatively . presenting symptoms included eight patients with pain , nine with sensory deficits , eight with motor deficits , and four with loss of reflexes .\nregarding patient workup , three received hip radiographs , four had cts , two had magnetic resonance imaging ( mris ) , and nine underwent emgs .\nten patients received operative intervention , whereas one was treated conservatively with a brace and one with no intervention . mechanisms of injury include three patients with mass formation adjacent to the construct , one patient with limb - lengthening injury , and seven patients with hardware migration and compression .\nof those with mass formation next to the construct , one was felt to be inflammatory pseudotumor whereas two were felt to be wear - related cysts caused by metal debris . after intervention\n, four patients made a full recovery of function , whereas six out of eight patients with preintervention motor deficits had persistent motor deficits and one without preintervention motor deficits developed a foot drop postoperatively .\nout of the nine patients with sensory deficits , four had persistent sensory loss after intervention .\npatients with delayed neuropathy varied in presentation with pain , sensory , and motor symptoms .\nmost patients were evaluated with an emg that can objectively quantify degree of motor compromise and aid in lesion localization . as the causes of delayed nerve injury are largely local anatomical changes , ct and mri can be helpful in identifying the cause of neuropathy .\nemg localization of the level of deficit , combined with screw malposition , suggested that it was the cause of the patient 's sensory and motor loss .\ndelayed neuropathy is a rare complication after primary tha that can be caused by hardware irritation as in the present case .\npatients can present with pain , sensory loss , motor loss , and decreased reflexes that are best worked up with emg to localize the area of neuropathy and imaging to identify the root source .\nresults from the literature show that operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function .", "answer": "background \n total hip arthroplasty ( tha ) is an established treatment for end - stage arthritis , congenital deformity , and trauma with good long - term clinical and functional outcomes . \n delayed sciatic nerve injury is a rare complication after tha that requires prompt diagnosis and management.methods \n we present a case of sciatic nerve motor and sensory deficit in a 52-year - old patient 2 years after index left tha . \n electromyography ( emg ) results and imaging with radiographs and ct of the affected hip demonstrated an aberrant acetabular cup screw in the posterior - inferior quadrant adjacent to the sciatic nerve.case description \n the patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement . \n a literature review identified 11 patients with late - onset neuropathy after tha . \n ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function.conclusions \n delayed neuropathy of the sciatic nerve is a rare complication after tha that is most often due to hardware irritation , component failure , or wear - related pseudotumor formation . \n operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function .", "id": 324} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntoday , the treatment of choice is surgical excision of the tongue , but before 1900 , surgery was often temida1 . only in 1673 niels\nthe size and shape of the teeth are directly influenced by the size of tongue3 .\nthe shape of the teeth is determined by forces employed on the teeth , especially the muscles of the tongue , lips and cheek . due to the effects caused by the aesthetic and functional macroglossia\nthe macroglossia is classified as true when there is excessive enlargement of the language and a relative when there is an imbalance between the size of the tongue and oral cavity , resulting in insufficient space for organ4 .\nthe goal is to establish technical bases associated with partial glossectomy orthodontic treatment of dentofacial deformity in patients with macroglossia .\nthree patients underwent orthognathic surgery associated with partial glossectomy from 1995 to 1999 , a multidisciplinary team - doctor and dentist .\nall patients had macroglossia relative and underwent clinical assessment taking into account the respiratory function , swallowing and speech deficit , as well as changes in dental occlusion and was also performed radiological evaluation .\nthe main problem was manifested by the presence of steep lower dent alveolar , destabilizing the use of dentures causing joint dysfunction with severe pain .\nshe underwent a single surgical intervention in the partial glossectomy and orthognathic surgery for targeting sub apical segment dent alveolar anterior inferior .\nthe main problem of the second patient was the anterior open bite accompanied by difficulty in breathing and articulation of words .\nafter treatment for orthodontic tooth alignment leveling , underwent surgery for a single suspension by corticotomy posterior maxillary le fort i type , reduction of mandibullary prognathism by sagittal technical branches , targeting sub apical posterior - inferior right and partial glossectomy .\nthe third patient had mandibullary prognathism and , during orthodontic treatment in preparation for orthognathic surgery , the surgery was anticipated , since the interposition of the tongue between the back teeth did not allow the evolution of orthodontic treatment .\nhe underwent a partial glossectomy to reduce the transverse diameter of the tongue and mandibullary prognathism by sagittal technical branches .\nwe used rigid skeletal fixation with titanium plates and screws so that patients could stay without intermaxillary block in the immediate postoperative period . to control tongue edema ,\nthe technique used consist of segmental resection along the median raphe of the tongue and suture by planes - figure 1 . as a routine\nthe symptoms regressed completely and all skeletal segments remained stable . \n demarcation and resection of the lingual and final appearance .\nthe classification of macroglossia is not yet consensus in the literature . according to shafer ( 1968)5 , or\nprimary congenital macroglossia is due to the excessive development of the musculature , which may or may not be associated with generalized muscular hypertrophy or unilateral hypertrophy . since the secondary macroglossia may occur as a result of a tumor in the tongue , as a diffuse hemangioma or lymphangioma , neurofibromatosis , and occasionally blocking efferent vessels in cases of malignant neoplasm of the tongue .\nwolford et al . ( 1996)6 refer to as macroglossia on pseudomacroglossia , separating it from the true macroglossia .\n( 1980)7 macroglossia consider the functional as a third classification , occurring when the language does not fit into the oral cavity after a surgical procedure .\nthe true when there are histological abnormalities associated with the increase of the tongue , such as vascular malformation , stretching and tumors .\nrelative macroglossia includes cases of apparent increase in volume without an explanation of the language exam , as in down syndrome .\nthe decision to refer the patient to partial glossectomy should be based on the volume of the language , mobility , position , function , symptoms , speech intelligibility , skeletal anterior open bite , interference in orthodontic treatment , drooling , swallowing and tongue recurrent trauma9 .\nthe language has increased in volume expansive effect on the lower dental arch , being blamed as the cause and maintenance of open bite , bimaxillary protrusion or diastemas10 .\nbeing interposed between the arches , is an important etiologic factor for malocclusion listed ( figures 2 and 3 ) . \n\na partial glossectomy performed simultaneously with mandibullary osteotomy for treatment of patients with mandibullary prognathism and anterior open bite is advantageous to prevent recidivas11 .\nthe tongue can cause deformity increased dental - muscle - skeletal , instability in orthodontic treatment and orthognathic surgery , masticatory disability , communication problems and respiratory6 .\nthere are several clinical and radiographic findings , but not all features are always present and their existence is not necessarily path gnomonic for the diagnosis of macroglossia .\nshould be included the clinical , radiographic and functional for the interference with speech , mastication , airway and stability of orthodontic treatment and orthognathic surgery .\nthere are basically three choices in the surgical sequence : ( i ) stage 1 : partial glossectomy , stage 2 : orthognathic surgery ( ii ) stage 1 : orthognathic surgery , stage 2 : partial glossectomy and ( iii ) partial glossectomy and orthognathic surgery in a single stage surgery .", "answer": "summary \n introduction : macroglossia is a condition which influences the size and shape of the teeth employed due to the forces on teeth . \n objective : to establish bases for the indication of partial glossectomy associated with orthodontic treatment and surgical dento - facial deformity in patients without tumors and down syndrome as a cause of macroglossia . \n \n case reports : three patients underwent orthognathic surgery associated with partial glossectomy under general anesthesia . \n all patients had macroglossia relative and underwent clinical assessment taking into account the respiratory function , swallowing and speech deficits and radiological evaluation . \n the technique used consist of segmental resection along the median raphe of the tongue and suture by planes . \n we used rigid skeletal fixation with titanium plates and screws so that patients could stay without intermaxillary block in the immediate postoperative period . \n were followed over five years . \n the symptoms regressed completely and all skeletal segments remained stable . \n \n discussion : the decision to refer the patient to partial glossectomy should be based on the volume of the language , mobility , position , function , symptoms , speech intelligibility , skeletal anterior open bite , interference in orthodontic treatment , drooling , swallowing and tongue trauma applicant .", "id": 325} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npari passu with the progress of science in medical education , simulation in medical education is also progressing in leaps and bounds .\nsomething which was hardly ever talked about even a couple of years ago has now become the new buzz word in medical education circles , and now india is also getting on the bandwagon .\nsimulation has been variably defined as the imitation of the operation of a real - world process or system over time ; an imitation of some real thing , state of affairs , or process for the practice of skills , problem solving , and judgment . \nthe aim of medical simulation training is to imitate reality , or rather , to mimic reality to the closest extent possible so that the learner is in a state of suspended disbelief and he believes himself to be undergoing a real experience .\nsimulation has been used at its greatest effect in pilot training - indeed , it is mandatory for all pilots of commercial aircraft to undergo refresher courses on flight simulators , regardless of their real flying experience .\nmedical simulation has unfortunately not kept up with the development of simulation in engineering systems , flight training , etc . however , this situation is now rapidly changing .\nthis change has been brought about by three main reasons : firstly , a big increase in student population in medical education , both at the undergraduate and post - graduate level .\nthis unprecedented growth has occurred in the past two decades ( mci vision 2015 ) .\napproximately 33,528 graduates pass out every year from these colleges ( mci annual report 20092010 ) .\n. there has also been legislation which limits the number of hours residents can now work , reducing further the opportunity for bedside learning .\nthe american medical association 's accreditation council for graduate medical education has limited the time that residents can be required to work to 80 h a week .\nalthough this action was intended to improve patient safety , it also reduced the number of patient - contact hours needed to train residents .\nsecondly , there is a growing awareness of patients of their rights and reluctance to be practiced upon and the growing incidence of medical litigation leading to a reduction in the number of available patients .\nfinally , there has been a huge technological improvement in the quality and variety of simulators .\nnow , high fidelity computerised human patient simulators have been developed by various companies ( e.g. simman by laerdal , the meti family of human patient simulators by cae health care ) , which mimic very realistically the response of human beings to physiological insults , whether it be an acute cardiac event , or a trauma event ; indeed , any disease process that affects the cardiovascular or respiratory system can be accurately modelled .\nsurgical simulators have been developed to practice laparoscopic surgery using a virtual reality environment ( e.g. the lapvr laparoscopic simulator by cae health care ) , which even provide haptic feedback ( a sense of tissue resistance ) .\n, many countries are now making certification on simulators mandatory before performing procedures on actual patients . even in india\n, the mci 2015 vision document says that a mandatory and desirable comprehensive list of skills has been planned and would be recommended for bachelor of medicine and bachelor of surgery ( mbbs ) graduate .\nthe educational technology section of the 2004 aem consensus conference for informatics and technology in emergency department health care concluded that there should be increasing use of web - based , virtual reality and human patient simulation in educating emergency medicine trainees .\nthe authors postulate the philosophy of see one , simulate many , do one competently , and teach everyone .\n there are now many articles on how simulation can be used in medical training .\na key challenge for surgical training is to provide conditions for effective learning without putting patients health at risk .\nsimulation presents an attractive solution , offering a safe , simulated clinical environment where the training agenda can be determined by the needs of the learner , not the patient .\nevidence is now available to suggest that simulation training actually improves clinical performance . in a review of simulation articles , it was found that four ( 3% ) journal articles provided evidence for the direct correlation of simulation validity with effective learning .\nanother study showed that the use of virtual reality surgical simulation to reach specific target criteria significantly improved the operating room ( or ) performance of residents during laparoscopic cholecystectomy .\nsimulation in wound management is still relatively in its infancy when compared to the use of simulation in other areas of medical education .\nit is however reasonable to believe that the use of simulation in wound management will result in improvement in wound care .\nsimulation in relation to wounds can be divided into use of simulation to study the effect of projectiles on tissue ( wound modelling ) and the use of simulation in the management of wounds .\nthe purpose of this article is to outline the present status of simulation related to wounds , in terms of their creation and management .\nmoulage is the art of creating mock injuries to simulate wounds . theatrical makeup and common everyday materials\nmoulage is commonly used in mass casualty and disaster drills to add realism to the simulation .\nit is reasonable to believe , though not proven , that the use of moulage would create a more realistic environment to enhance learning in mass casualty and other trauma situations . as far back as in 1964 , omissions and deficiencies in disaster ability were dramatically and conclusively revealed by use of what appeared to be a \nlive disaster setting with smoke , fire , explosions ; adverse weather and light conditions ; realistically simulated casualties especially prepared not only to look but also to act the part .\nmoulage by author ( drp ) showing bleeding thigh wound and evisceration on metiman ( cae health care ) mannequin\nanother area where simulation is used in wounds is to simulate the effect of injuring agents on the body so as to understand the various forces that are at work on the tissues during the causation of an injury .\nthis would help in accurate wound assessment and anticipation of likely tissue damage if the causative agent is known .\nwork has mainly been done on cavitating injuries produced by high - velocity projectiles . because gelatin and glycerin soap have approximately the same density as human tissue , the gunshot effects in them are comparable with those in human tissue . the experiments with these substitutes make it possible to understand what happens to the human body as the result of , for example , a penetrating gunshot .\nsome other authors have used transparent gel candles [ 15% kraton ( polymers ) in 85% white paraffin oil ] for the same purpose . a synthetic skin skull\n brain model has been developed to simulate gunshot wounds to the head in such a realistic manner as to reconstruct the specific physical characteristics of a given trauma , including its progressive formation .\nthis model uses a silicon cap containing synthetic fibres for artificial skin , a layered polyurethane sphere for the skull ( containing the outer and inner tables as well as the diploe ) , a periosteum of latex and the brain itself is simulated with ordnance gelatin .\nhigh fidelity simulators are now available which can mimic the physiological effects of wounds on the body .\nthe aim of management of a wounded individual in the emergency department is mainly to correct and prevent the life - threatening physiological derangements associated with the wound like airway obstruction , hypovolemia , respiratory distress , etc . as such\nthese physiological derangements can be mimicked extremely realistically by these high fidelity systems , examples of which are the meti family of mannequins from cae health care or the simman family from laerdal .\nthese simulators are used the world over to train emergency medical care providers , medical students , post - graduates and practicing physicians and surgeons in emergency trauma management [ figure 2 ] .\nmilitary specific simulators ( e.g. caesar from cae healthcare ) are now in advanced stages of development to train soldiers with non - medical backgrounds at the point of injury . \njohn 's ambulance team ( malaysia ) demonstration of trauma scenario on ecs ( meti ) simulator\nthere are a few articles on the emergence of simulation in wound management , which deal essentially with teaching learners local wound management .\nthis includes wound dressing techniques , performance of local surgery like escharotomy or wound debridement .\nwound management simulators can be divided into basic part task trainers which use low - technology solutions that are cheap and high - technology virtual reality simulators which , of course , will be much more expensive . the low - technology solutions are discussed first , followed by the high - technology virtual reality solutions .\nsimulated wounds have been created on animal models like pig trotters to teach the technique of wound debridement . a simulated wound covered with thick slough\ncan be created on a pig trotter by excising an area of skin and then applying a layer of hydrocolloid paste ( e.g. adapttm , hollister ) on the denuded area . a layer of toothpaste\nmay then be applied and covered with a piece of glad wrap to simulate the application of emla cream . a small curette\nis then used to debride the wound as in a human patient , after washing away the layer of toothpaste ( = topical anaesthetic ) .\nanother study has created a simulated abscess in chicken breast by injecting mock purulent material under the chicken breast skin .\nthe author felt that this new simulation model may be an effective tool to teach skin abscess management .\nphysicians who evaluated the simulated abscess found that it replicates the classic palpable fluctuance and ultrasound findings of an actual abscess , and it can be surgically incised and drained in a similar fashion .\nyet another researcher has used an orange to simulate debridement - the student is required to remove the peel and the white fibres ( representing slough ) off the orange without puncturing the inner orange itself . burn wounds offer a challenge to learners in terms of local wound care , and as a result\nthis helps train burn care trainees in the management of such wounds , specifically to perform escharotomy .\na major technological development has been that of a thigh wound virtual reality model by delp et al .\nthey have used the data from the visible human project as the basis of reconstruction of the thigh anatomy , on which they superimposed wound models of bullet wounds gleaned from data available in the literature .\nfunctional consequences of the injuries were also modelled , which provided both short - term consequences as well as long - term disability of the simulated patient .\nthe user could interact with the virtual thigh model using virtual surgical instruments from a virtual tray to stop the bleeding , assess muscle bleeding and contractility , perform debridement , align bone , etc .\nthe overall effect on the patient 's physiology was also calculated and displayed in terms of vital signs readouts , which changed depending upon appropriate treatment , e.g. control of bleeding , etc .\nthe virtual reality medical center ( vrmc ) conceptualised and developed a unique injury simulator as an adjunct to current combat medic training .\nthis initial technology , called injury creation science ( ics ) , very realistically simulated a number of battlefield injuries such as amputations , eviscerations , blast injuries , punctures and burns . since the initial prototypes , vrmc has developed this technology into wearable \npart - task trainers that simulate injuries as well as allow combat medics to practice actual medical procedures common to the battlefield .\nthe procedures currently available or under development include treatment of pneumothorax , hemoperitonium and gunshot wounds to an artery . by integrating medical science with cutting - edge simulation and training technologies , realistic prosthetic tissue , wounds and part - task trainers\none of the major issues with wounds is the risk of hospital - acquired wound infections , which are usually preventable by simple personal hygiene techniques .\nunfortunately , many hospital workers are either unaware of them or unwilling to follow these steps .\ntraining of all hospital staff to prevent cross infection is therefore high on the agenda for most hospital administrators , impinging as it does on patient safety .\nif the movement of bacteria that cause wound infection , and their removal from hands and other inanimate hospital objects could be seen , then it would be a very useful training tool and could markedly increase staff compliance with hygiene measures .\nthis is exactly what was done in one study wherein ultraviolet polyethylene microspheres were able to simulate the spread of bacteria through direct and indirect contact on different surfaces and had the ability to be washed off under specific hand washing guidelines .\nthe authors felt that due to the positive results , the use of microspheres as a simulator of bacterial presence and spread should be explored further in order to improve hand washing techniques and compliance .\na simulation - based training system for surgical wound debridement has been developed and comprises a multimedia introduction , a surgical simulator ( tutorial component ) and an assessment component .\nthe multimedia training component describes varieties of wound categories ( e.g. burns , lacerations , etc . ) , methods of debridement ( e.g. sharp , mechanical , etc . ) and equipment / materials used in the procedure .\nthis module provides the pedagogical context for skills training and assessment , linking together all of the required elements for mastering the procedure .\na software virtual agent is included and performs the role of an instructor by providing verbal guidance and assessment feedback . designed to be comprehensive in order to reduce the need for a more senior instructor , the software addresses the patient 's condition , initial description of the injury , and provides instruction on operation of the simulator .\nspecific instructions cover the removal of foreign objects with forceps , scrubbing with a brush , rinsing with saline solution and the maintenance of sterility .\ntrainees are instructed to remove debris with forceps , scrub with a brush and rinse with saline solution to maintain sterility . in conclusion ,\nincreasing sophistication in simulation technology has been also used in simulation of wounds , both in wound modelling and wound management .\nthe available simulators include low - technology solutions and high - technology virtual reality simulators , all of which train learners in the art of wound management .\nhowever , this technology is yet to be validated in wound management to see if simulator training can result in better management of wounds in actual patients .\nfuture developments would include research on application of simulator training to real patient care , and the development of better technology to make virtual reality simulators even more realistic by the improvement of design , graphics and haptic feedback .", "answer": "simulation in medical education is progressing in leaps and bounds . \n the need for simulation in medical education and training is increasing because of a ) overall increase in the number of medical students vis - - vis the availability of patients ; b ) increasing awareness among patients of their rights and consequent increase in litigations and c ) tremendous improvement in simulation technology which makes simulation more and more realistic . \n simulation in wound care can be divided into use of simulation in wound modelling ( to test the effect of projectiles on the body ) and simulation for training in wound management . \n though this science is still in its infancy , more and more researchers are now devising both low - technology and high - technology ( virtual reality ) simulators in this field . \n it is believed that simulator training will eventually translate into better wound care in real patients , though this will be the subject of further research .", "id": 326} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunilateral absence of pulmonary artery ( uapa ) is a rare congenital abnormality , with an estimated prevalence of 1 in 200,000 .\nsome patients with uapa are totally asymptomatic while others may have severe pulmonary hypertension , hemoptysis , congestive heart failure , and cyanosis .\nwe report a 2.5-year - old girl with congenital absence of the right pulmonary artery with associated congenital cystic adenomatoid malformation ( ccam ) of the right lower lobe , patent ductus arteriosus ( pda ) , and atrial septal defect ( asd ) , who presented with ortner 's syndrome due to severe pulmonary hypertension .\na 2.5-year - old girl presented with hoarseness of voice noticed since 3 months of age , breathlessness for the past 15 days and failure to thrive .\nshe had been admitted elsewhere for lower respiratory tract infection at 3 months of age .\nthe child was noticed to have a weak cry and an exaggerated suck - rest - suck cycle and sweating over the forehead while feeding .\npulse oximetry in room air showed an oxygen saturation varying between 60% and 70% in all four limbs .\nweight and height were 7 kg and 77 cms , respectively both below the third percentile for age and sex .\nan ejection systolic murmur grade 3 was heard in the right parasternal region in the fourth and fifth intercostal spaces .\nthe liver was palpable 2 cm below the right costal margin in the mid - clavicular line .\nchest x - ray [ figure 1 ] revealed cardiomegaly with a cardio - thoracic ratio of 0.6 and deviation of the trachea and mediastinum to the right .\ntwo - dimensional ( 2d ) echocardiography showed decreased flow in the right pulmonary artery , a small asd with a right - to - left shunt , and a dilated right atrium and right ventricle with severe tricuspid regurgitation , suggestive of severe pulmonary hypertension .\nmultiple detector computerized tomography aortogram [ figure 2 ] confirmed the findings of asd with pulmonary hypertension , absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of ccam in the right lower lobe .\nchest x - ray posterioranterior view showing cardiomegaly and shift of trachea and mediastinum to the right multiple detector computerized tomography aortogram showing absent right pulmonary artery , and cystic lesions in the right lower lobe suggestive of congenital cystic adenomatoid malformation ( arrow ) of lung at admission , the patient was started on oxygen , furosemide , enalapril and intravenous cefotaxime , on a provisional diagnosis of congenital cyanotic heart disease with increased pulmonary blood flow , lower respiratory infection , and congestive cardiac failure . despite these measures ,\nthere was persistent hypoxemia and worsening of cardiac failure in the form of tachycardia and bilateral basal crepitations .\nthe child was intubated and ventilated and started on pressors , but sustained a cardiac arrest on the 4 hospital day from which she could not be resuscitated .\ncomplete arrest of pulmonary artery supply results in the arrest of early bronchial development leading to agenesis of the affected lobe or segment .\npulmonary agenesis is usually unilateral , right sided absence of pulmonary artery being more common .\nmore than 50% of children with pulmonary agenesis have associated congenital anomalies that involve the cardiovascular ( pda and patent foramen ovale ) , gastrointestinal , skeletal , and genitourinary systems . our patient had asd and pda .\nwhile some patients with uapa are totally asymptomatic , others may have severe pulmonary hypertension , hemoptysis , congestive heart failure , and cyanosis .\nchest x - ray may show an absent hilar shadow , a shrunken affected lung , and shift of the mediastinum to the affected side .\nan early interruption in the development of the pulmonary artery could result in the continued development of the primitive capillary supply to a region of the lung with resultant abnormal development of the supplied region .\nthe magnitude of the insult would determine the exact development of the affected lung tissue and final blood supply , resulting in pulmonary sequestration , ccam , or a combination of the two lesions .\nthe incidence of pulmonary hypertension in patients with isolated uapa varies between 18% and 44% . in patients with uapa with pda as in our patient , the incidence of pulmonary hypertension was observed to be as high as 86% , those with pulmonary hypertension dying at an early age .\nortner syndrome or cardiovocal syndrome refers to hoarseness of voice due to recurrent laryngeal nerve paralysis secondary to cardiovascular disease .\nthis syndrome was first described by ortner in 1897 in two patients who had mitral stenosis and left recurrent laryngeal nerve paralysis .\nthe syndrome has since been described in adults with various cardiovascular disorders , but reports in children are less common .\nthe pulmonary artery , enlarged due to pulmonary hypertension , has been implicated as the main mechanism of nerve injury .\nfetterolf and norris studied the anatomic relations of the left recurrent laryngeal nerve in cadavers and concluded that the nerve must be squeezed between the enlarged left pulmonary artery and the aorta or ligamentum arteriosum .\nunilateral absence of pulmonary artery should be considered in the differential diagnosis of children who present with cyanosis , pulmonary hypertension , or recurrent lower respiratory tract infections .", "answer": "we report a 2.5-year - old girl who presented with hoarseness of voice since 3 months of age and failure to thrive . \n chest x - ray showed cardiomegaly with a deviation of the trachea and mediastinum to the right side . \n two - dimensional echocardiography showed decreased flow across the right pulmonary artery , a small atrial septal defect ( asd ) with a right - to - left shunt , and a dilated right atrium and right ventricle with severe tricuspid regurgitation suggestive of severe pulmonary hypertension . \n a silent large patent ductus arteriosus was also seen . \n multiple detector computerized tomography aortogram confirmed the findings of absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of congenital cystic adenomatoid malformation in the right lower lobe . \n hoarseness of voice was due to the left vocal cord palsy probably secondary to severe pulmonary hypertension ( ortner 's syndrome ) .", "id": 327} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhealthy skin protects against the effects of environmental hazards , such as ultraviolet radiation in sunlight , low humidity , and wind.2 dry skin affects many people , occurring when skin loses its water content , causing the skin to appear dry , rough , and scaly , possibly with reddening , cracking , and itching.3 when the skin becomes dry , the epidermal layer loses its ability to retain moisture . without protection or treatment ,\nthe skin can not repair itself , leading to persistently dry skin.4 several treatments can be used to restore dry skin or protect it from dryness .\na topically applied moisturizer is the main treatment , which makes the epidermal layer of the skin softer and more pliable by enhancing hydration and decreasing water evaporation .\napplication of an occlusive mask to the skin can also improve hydration and protect against water loss from the epidermis.5 masks can be produced from various sources .\ncellulose masks obtained from natural sources , such as bacteria , are of interest because of their low toxicity and biodegradable properties .\nacetobacter xylinum , a bacterium , can produce acid from glucose and synthesize cellulose.6 it creates cellulose from sugars and related substrates via the pentose cycle.7 bacterial cellulose has been widely used as a stabilizer in foods and cosmetics . in the form of a film , it can be used in surgical procedures and for dental implants.8 recently , bacterial cellulose obtained from acetobacter xylinum culture was characterized and found to be composed of long , smooth , and oriented fibrils and to exhibit considerable thermal stability.9 therefore , it was of interest for use as a bacterial cellulose cosmetic device , in particular as a facial mask . the objectives of this study were to determine the in vivo efficacy of a cellulose mask obtained from acetobacter xylinum in changing skin characteristics and to evaluate user satisfaction after a single application .\nif a product can provide the expected results and achieve a high level of user satisfaction after single use , it is likely that the user will purchase that product again .\nbriefly , broken - milled rice ( oryza sativa ) was used as the feeding substrate and distilled water was used as a medium for growth of acetobacter xylinum . under appropriate incubation , the bacterium could synthesize cellulose .\nthe cellulose with absorbed water obtained was cut into a face shape with holes for the eyes , nose and mouth at the correct positions .\nthe finished products were sterilized by steam in an autoclave at 121c for 15 minutes .\nthe manufacturer reported that the masks were nonirritant and satisfactory when studied in 16 thai women.10 thirty healthy thai volunteers aged 2140 years participated in testing of the efficacy of the cellulose mask for improvement of skin characteristics .\ntwenty - three , five , and two volunteers were in the age ranges of 2125 , 2630 , and 3140 years , respectively .\nthe sample size was estimated to be sufficient to detect a difference between two population means when the probability of type i error ( ) and that of type ii error ( ) was set at 0.05 and 0.20 , respectively .\nthe study was carried out with the approval of the ethics committee of the faculty of pharmaceutical sciences at prince of songkla university , songkhla , thailand .\nall volunteers gave their informed written consent and underwent testing for any skin irritation that might be caused by the cellulose mask before the study .\nno skin irritation occurred when the cellulose mask was applied to the lateral arm for 24 hours , so all volunteers were able to be included in the study .\nthe experiment was done in a laboratory room where the temperature and relative humidity was controlled at 25c and 50% , respectively .\nfor the first test , volunteers in the group were assigned to apply moist towels to the face for 25 minutes , while volunteers in the other group were assigned to apply the trial masks to the face for the same time period .\none week later the experiment was repeated , with the volunteers changing over to the alternative treatment .\nskin moisture , sebum , elasticity , texture , dullness , and desquamation levels were assessed before applying the sample and five minutes after removing it using a tool normally used as part of routine skin counseling ( moritex corporation , tokyo , japan).11 the skin counseling system consists of a touch screen computer with a sensor and a scope to evaluate sebum , moisture , elasticity , texture , and dullness of the skin . the values obtained are reported as percentages , and ranked as low , medium and high , in comparison with reference values in a population of the same age range provided by the manufacturer . to evaluate desquamation , a 2 cm 1 cm\nthe sticker was applied to the experimental area of skin for one minute and then peeled off .\nafterwards , the surface of the sticker containing a sample of the skin from each volunteer was attached to the lens window of the scope , which was then used to rate the condition of the skin .\ntexture , dullness , and desquamation were ranked as a , b , or c good , fair , or poor , respectively , when compared with reference values . at the end of the study ,\nall volunteers completed a questionnaire rating their degree of satisfaction with the cellulose mask on a five - point scale ( excellent = 5 , good = 4 , fair = 3 , poor = 2 , very poor = 1 ) .\nthe paired t - test and t - test were used to identify statistically significant differences in skin characteristics before and after using the trial product and between the trial product and the control , respectively .\nbriefly , broken - milled rice ( oryza sativa ) was used as the feeding substrate and distilled water was used as a medium for growth of acetobacter xylinum . under appropriate incubation , the bacterium could synthesize cellulose .\nthe cellulose with absorbed water obtained was cut into a face shape with holes for the eyes , nose and mouth at the correct positions .\nthe finished products were sterilized by steam in an autoclave at 121c for 15 minutes .\nthe manufacturer reported that the masks were nonirritant and satisfactory when studied in 16 thai women.10\nthirty healthy thai volunteers aged 2140 years participated in testing of the efficacy of the cellulose mask for improvement of skin characteristics .\ntwenty - three , five , and two volunteers were in the age ranges of 2125 , 2630 , and 3140 years , respectively .\nthe sample size was estimated to be sufficient to detect a difference between two population means when the probability of type i error ( ) and that of type ii error ( ) was set at 0.05 and 0.20 , respectively .\nthe study was carried out with the approval of the ethics committee of the faculty of pharmaceutical sciences at prince of songkla university , songkhla , thailand .\nall volunteers gave their informed written consent and underwent testing for any skin irritation that might be caused by the cellulose mask before the study .\nno skin irritation occurred when the cellulose mask was applied to the lateral arm for 24 hours , so all volunteers were able to be included in the study .\nthe experiment was done in a laboratory room where the temperature and relative humidity was controlled at 25c and 50% , respectively .\nfor the first test , volunteers in the group were assigned to apply moist towels to the face for 25 minutes , while volunteers in the other group were assigned to apply the trial masks to the face for the same time period .\none week later the experiment was repeated , with the volunteers changing over to the alternative treatment .\nskin moisture , sebum , elasticity , texture , dullness , and desquamation levels were assessed before applying the sample and five minutes after removing it using a tool normally used as part of routine skin counseling ( moritex corporation , tokyo , japan).11 the skin counseling system consists of a touch screen computer with a sensor and a scope to evaluate sebum , moisture , elasticity , texture , and dullness of the skin .\nthe values obtained are reported as percentages , and ranked as low , medium and high , in comparison with reference values in a population of the same age range provided by the manufacturer . to evaluate desquamation , a 2 cm 1 cm\nthe sticker was applied to the experimental area of skin for one minute and then peeled off .\nafterwards , the surface of the sticker containing a sample of the skin from each volunteer was attached to the lens window of the scope , which was then used to rate the condition of the skin .\ntexture , dullness , and desquamation were ranked as a , b , or c good , fair , or poor , respectively , when compared with reference values .\nat the end of the study , all volunteers completed a questionnaire rating their degree of satisfaction with the cellulose mask on a five - point scale ( excellent = 5 , good = 4 , fair = 3 , poor = 2 , very poor = 1 ) .\nthe paired t - test and t - test were used to identify statistically significant differences in skin characteristics before and after using the trial product and between the trial product and the control , respectively .\nthe cellulose mask was a translucent patch which could be fitted onto the face as demonstrated in figure 1 .\nthe skin sebum level after moist towel application was 51.43 12.24% and after using the trial cellulose mask was 50.57 12.09% .\nthe skin elasticity level after moist towel application was 44.30 12.73% and after using the trial cellulose mask was 46.70 8.78% .\nthe skin moisture content after moist towel application was 47.33 7.81% and after using the trial cellulose mask was 61.23 10.84% .\nit was also noted that , after using the cellulose mask , skin moisture levels increased by between 7% and 28% , without changes in the other parameters , ie , sebum and elasticity levels , as shown in table 1 .\ndata for skin texture and dullness and keratin desquamation are also reported in table 1 .\nthere was no significant difference between grades obtained for skin texture after moist towel application and those after application of the cellulose mask .\nskin transparency improved in eight of the 30 volunteers ( 26.7% ) when using the cellulose mask .\nhowever , there was no detectable change in degree of pigmentation between the two treatments .\nsigns of keratin desquamation were not significantly different after moist towel application , but changed from grade b \nc to grade a in seven cases ( 23.3% ) after using the cellulose mask .\nall the volunteers completed and returned their satisfaction questionnaires , the answers to which are reported in table 2 .\nthese results indicate that a single application of the cellulose mask did not significantly reduce sebum levels or increase elasticity of the skin ( p > 0.05 ) . however , it did significantly enhance moisture uptake ( p < 0.05 ) .\nthe water content in formulations or devices used for skin hydration is an important consideration.12 like many moisturizers , cellulose masks can absorb moisture from the environment.13 using the cellulose mask , absorption of moisture by the skin occurred due to the high concentration gradient of water between the mask and the skin . the occlusive effect of the cellulose mask administered to facial skin for 25 minutes can reduce transepidermal water loss,14 with efficacy of moisture uptake varying according to the skin condition of the individual volunteers .\nthe increased skin moisture content achieved by the cellulose mask did not improve skin texture , dullness , and desquamation significantly when compared with moist towel application ( p > 0.05 ) .\nhowever , a minority of the volunteers did achieve improved skin transparency and desquamation after applying the cellulose mask , the reasons for which are unclear .\nit is possible that different subjects responded differently to hydration after topical application of the cellulose mask depending on their general health , skin condition , age , gender , and possibly other factors . in a previous study\n, it was reported that eight of thirty - four volunteers had a significantly greater reduction in eye puffiness after application of caffeine gel than after placebo ( p < 0.05 ) , while most volunteers did not show a differential response to these two products.15 the results from our questionnaires demonstrated that the odor , color , and texture of the cellulose masks were acceptable to the subjects , the majority of whom rated the cellulose mask comfortable to use and able to provide skin hydration within an acceptable period .\noverall , user satisfaction with the cellulose mask was rated as good . in the future , it is possible that cosmetically active compounds , eg , for skin - whitening and antiageing , will be able to be incorporated into such cellulose masks as nanoformulations , which are likely to meet user demands further.16,17\nthe cellulose mask derived from acetobacter xylinum could be used as a natural cosmetic product in order to increase moisture uptake in the skin .\nsingle application of the cellulose mask significantly enhanced moisture uptake by the skin when compared with moist towel application ( p < 0.05 ) . however , it did not change skin characteristics to a significant degree .\nthe responses to the satisfaction questionnaire used in this trial suggest that the cellulose mask is acceptable to users .", "answer": "backgroundcellulose masks obtained from natural sources such as bacteria are of interest as cosmetic devices for the treatment of dry skin because they not only improve hydration of the skin , but have low toxicity and are biodegradable . \n the aims of this study were to determine the in vivo effects of a cellulose mask obtained from acetobacter xylinum on skin characteristics and to evaluate user satisfaction with the product.methodsthirty healthy thai volunteers aged 2140 years participated in the study . \n the volunteers were randomly separated into a control group and an experimental group . for the control group , \n volunteers were assigned to apply moist towels to the face for 25 minutes . \n for the experimental group , the volunteers were assigned to apply the masks , ie , translucent patches which could be fitted onto the face for the same period . \n the following week , the groups were changed over to the alternative treatment . \n skin moisture , sebum , elasticity , texture , dullness , and desquamation levels were assessed using a system used for routine skin counseling before applying the trial product and five minutes after its removal . \n degree of satisfaction with use of the cellulose mask was investigated using a five - point rating scale.resultsthe cellulose mask increased moisture levels in the skin significantly more than moist towels ( p < 0.05 ) after a single application . no obvious effects on other skin characteristics were found . \n the cellulose mask product rated around 4/5 on the satisfaction rating scale.conclusionsa single application of the trial cellulose mask enhanced moisture uptake by facial skin . \n users also reported being satisfied with the trial product .", "id": 328} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmodern insulin analogues are a convenient new approach or tool to glycaemic control , associated with low number of hypoglycaemia and favourable weight change .\na1chieve , a multinational , 24-week , non - interventional study , assessed the safety and effectiveness of insulin analogues in people with t2 dm ( n = 66,726 ) in routine clinical care .\nplease refer to editorial titled : the a1chieve study : mapping the ibn battuta trail ..\nthe patient characteristics for the entire cohort divided as insulin - nave and insulin users is shown in the table 1 .\nthe majority of patients ( 81.1% ) started on or were switched to biphasic insulin aspart .\nother groups were insulin detemir ( n = 22 ) , insulin aspart ( n = 6 ) , basal insulin plus insulin aspart ( n = 2 ) and other insulin combinations ( n = 4 ) . overall demographic data after 24 weeks of treatment , overall hypoglycaemia decreased for both insulin user ( from 30.1 events / patient - year to 13.8 events / patient - year ) and insulin nave ( from 24.9 events / patient - year to 12.7 events / patient - year ) groups .\nthe hypoglycaemia incidence in insulin naive group at 24 weeks was lower than that observed in insulin users at baseline .\nalso a decrease in body weight was observed for both the groups at 24 weeks [ tables 2 and 3 ] .\nall parameters of glycaemic control improved from baseline to study end in the total cohort [ table 4 ] .\noverall efficacy data of the total cohort , 146 patients started on biphasic insulin aspart ogld , of which 95 ( 65.1% ) were insulin nave and 51 ( 34.9% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events or episodes increased for both the groups ( insulin nave : from 26.4 events / patient - year to 14.7 events / patient - year and insulin users : from 29.6 events / patient - year to 14.1 events / patient - year ) .\nquality of life improved at the end of the study [ tables 5 and 6 ] .\nbiphasic insulin aspartoral glucose - lowering drug safety data all parameters of glycaemic control improved from baseline to study end in those who started on or were switched to biphasic insulin aspart for both insulin nave and insulin user groups [ table 7 ] .\nbiphasic insulin aspartoral glucose - lowering drug efficacy data of the total cohort , 2 patients started on or were switched to basal + insulin aspart and both of them were insulin users .\nof the total cohort , 22 patients started on insulin detemir ogld , of which 17 ( 77.3% ) were insulin nave and 5 ( 22.7% ) were insulin users .\nafter 24 weeks of starting or switching to insulin detemir , hypoglycaemic events decreased for both insulin nave ( from 0.4 events / patient - year to 0.6 events / patient - year ) and insulin user ( from 2.9 events / patient - year to 1.9 events / patient - year ) group .\nquality of life improved at the end of 24 weeks [ tables 8 and 9 ] .\ninsulin detemiroral glucose - lowering drug safety data all parameters of glycaemic control improved from baseline to study end in those who started on or were switched to insulin detemir oglds for insulin - nave group [ table 10 ] .\ninsulin detemiroral glucose - lowering drug efficacy data of the total cohort , 6 patients started on insulin aspart ogld of which 1 ( 16.7% ) was insulin nave and 5 ( 83.3% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 13.0 events / patient - year to 0.0 events / patient - year for insulin user group [ tables 11 and 12 ] .\nof the total cohort , 146 patients started on biphasic insulin aspart ogld , of which 95 ( 65.1% ) were insulin nave and 51 ( 34.9% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events or episodes increased for both the groups ( insulin nave : from 26.4 events / patient - year to 14.7 events / patient - year and insulin users : from 29.6 events / patient - year to 14.1 events / patient - year ) .\nquality of life improved at the end of the study [ tables 5 and 6 ] .\nbiphasic insulin aspartoral glucose - lowering drug safety data all parameters of glycaemic control improved from baseline to study end in those who started on or were switched to biphasic insulin aspart for both insulin nave and insulin user groups [ table 7 ] .\nof the total cohort , 2 patients started on or were switched to basal + insulin aspart and both of them were insulin users .\nof the total cohort , 22 patients started on insulin detemir ogld , of which 17 ( 77.3% ) were insulin nave and 5 ( 22.7% ) were insulin users .\nafter 24 weeks of starting or switching to insulin detemir , hypoglycaemic events decreased for both insulin nave ( from 0.4 events / patient - year to 0.6 events / patient - year ) and insulin user ( from 2.9 events / patient - year to 1.9 events / patient - year ) group .\nquality of life improved at the end of 24 weeks [ tables 8 and 9 ] .\ninsulin detemiroral glucose - lowering drug safety data all parameters of glycaemic control improved from baseline to study end in those who started on or were switched to insulin detemir oglds for insulin - nave group [ table 10 ] .\nof the total cohort , 6 patients started on insulin aspart ogld of which 1 ( 16.7% ) was insulin nave and 5 ( 83.3% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 13.0 events / patient - year to 0.0 events / patient - year for insulin user group [ tables 11 and 12 ] .\nour study reports improved glycaemic control following 24 weeks of treatment with any of the insulin analogues ( biphasic insulin aspart ; insulin detemir ; insulin aspart ) with or without ogld .\nbodyweight decreased and quality of life improved after 24 weeks in the total cohort . though the findings are limited by number of patients , still the trend indicates that insulin analogues can be considered effective and possess a safe profile for treating type 2 diabetes in oriental morocco .", "answer": "background : the a1chieve , a multicentric ( 28 countries ) , 24-week , non - interventional study evaluated the safety and effectiveness of insulin detemir , biphasic insulin aspart and insulin aspart in people with t2 dm ( n = 66 726 ) in routine clinical care across four continents.materials and methods : data was collected at baseline , at 12 weeks and at 24 weeks . this short communication presents the results for patients enrolled from oriental , morocco.results:a total of 180 patients were enrolled in the study . \n four different insulin analogue regimens were used in the study . \n study patients had started on or were switched to biphasic insulin aspart ( n = 146 ) , insulin detemir ( n = 22 ) , insulin aspart ( n = 6 ) , basal insulin plus insulin aspart ( n = 2 ) and other insulin combinations ( n = 4 ) . at baseline glycaemic control was poor for both insulin nave ( mean hba1c : 9.0% ) and insulin user ( mean hba1c : 8.8% ) groups . \n after 24 weeks of treatment , both the study groups showed improvement in hba1c ( insulin nave : 1.7% , insulin users : 1.6% ) . \n sadrs including major hypoglycaemia did not occur in any of the study patients.conclusion:starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia .", "id": 329} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nseptic shock is consistently the most common causative factor identified for acute kidney injury ( aki ) in critical illness , and has been associated with nearly 50% of cases internationally . despite advances in our understanding of the pathophysiology of septic aki ,\ntreatment aimed at reversing or preventing septic aki remains primarily based on supportive haemodynamic management . in the previous issue of critical care , legrand and colleagues examine the association between haemodynamic targets of resuscitation ( cardiac output , mean or diastolic blood pressure , central venous pressure ( cvp ) and central venous oxygen saturation ) and development or persistence of aki in a single centre study of patients with septic shock admitted to a surgical icu .\nthe authors found that only higher cvp and low diastolic blood pressure were associated with increased risk of development of new aki , or persistence of renal dysfunction present at icu admission . in these patients\nimportantly , the association between cvp and aki remained when potentially confounding effects of positive fluid balance and higher positive end - expiratory pressure were accounted for in a multivariable analysis .\nso , a 5 mmhg increase in cvp predicted 2.7-fold odds of new or persistent aki .\nfurthermore , when the association between different levels of mean cvp and aki was examined in a non - parametric logistic regression , there was a trend for higher cvp to be associated with worse renal outcome for all levels of cvp from 4 mmhg upward , so that a cvp of 15 mmhg was associated with an approximately 80% risk of new or persistent aki , compared to approximately 30% at a cvp of 6 mmhg .\nthese findings are important because current surviving sepsis campaign guidelines recommend fluid resuscitation of patients with sepsis - induced tissue hypoperfusion to target a cvp of 8 to 12 mmhg ( or 12 to 15 mmhg in mechanically ventilated patients ) within 6 hours of presentation . in patients with sepsis - induced hypotension\nthe rationale for cvp targeted fluid resuscitation is to ensure ' adequate cardiac preload and hence maintain cardiac output and organ perfusion .\nhowever , absolute levels or changes in cvp poorly predict cardiovascular response as sepsis - induced hypotension is multi - factorial , related to changes in myocardial performance , vascular tone , regional blood flow distribution , venous reservoir capacity and capillary permeability . in contrast\n, elevated cvp will cause a direct and predictable increase of renal venous pressure that , experimentally , has been associated with elevated renal interstitial and intra - tubular pressure .\nresultant renal venous congestion can reduce renal blood flow ( lower trans - renal pressure gradient ) and decrease the pressure gradient for ultrafiltration ( higher intra - tubular pressure ) . in septic shock ,\n. aggressive fluid resuscitation beyond reversal of hypovolaemia to arbitrary cvp targets could result in increased venous congestion without substantial benefit to forward renal perfusion , thus predisposing to renal dysfunction .\nthe association between elevated cvp and renal dysfunction has been made previously in the setting of chronic cardiac failure .\nnow legrand and colleagues have provided evidence that such an association is observed in septic shock and its treatment .\ntheir findings are also in accord with secondary analysis of the vasopressin in septic shock trial , which reported that a more positive fluid balance and elevated cvp were associated with increased mortality in patients with septic shock even when accounting for differences in baseline illness severity and demographics .\nalthough these observational findings are hypothesis - generating rather than confirmatory , they add weight to the literature suggesting the adverse effects of fluid overload in critical illness and aki in particular , effects that may be mediated in part by venous congestion causing impaired organ function .\nit is now important to determine whether uncritical pursuit of cvp targets such as those advocated by the surviving sepsis campaign might , in some patients , add insult to sepsis - induced organ injury .\nprospective data are required to evaluate the true contribution of raised venous pressure to renal and other organ dysfunction and to determine better endpoints for fluid resuscitation in sepsis .\nrajkumar rajendram bsc mbbs mrcp frca fficm , specialty registrar in anaesthesia , royal free hospital , london .\njohn r prowle ma msc md mrcp fficm , consultant in renal medicine and intensive care , the royal london hospital , london .", "answer": "in critical illness , septic shock is a contributing factor in nearly half of all cases of acute kidney injury ( aki ) . \n traditional approaches to prevention of organ dysfunction in early sepsis have focused on prevention of hypoperfusion by optimisation of systemic haemodynamics , primarily by fluid resuscitation . \n fluid administration to a target central venous pressure ( cvp ) of 8 to 12 mmhg ( 12 to 15 mmhg in mechanically ventilated patients ) is currently recommended for the early resuscitation of septic shock . \n however , in the previous issue of critical care , legrand and colleagues report that higher cvp in the first 24 hours of icu admission with septic shock was associated with increased risk for development or persistence of aki over the next 5 days . \n this study highlights a potential association between venous congestion and the development of septic aki , suggesting that cvp - targeted fluid resuscitation in septic shock might not be beneficial for renal function .", "id": 330} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe fda - approved da vinci surgical system is a novel approach to perform minimally invasive surgery and is considered a second revolution in surgery after the introduction of laparoscopic surgery .\nthis system was introduced in april 2003 at our institution , with 90 pediatric patients undergoing a variety of procedures performed by our surgical group . among these procedures ,\nseveral reports have been published on this subject , concluding that it is a feasible , safe alternative . despite some of its potential benefits\n, there has yet to be any improvement shown by using the robot over the standard laparoscopic or open technique .\nour objective in this study was to compare results using the robot system with that of laparoscopic and open techniques in our pediatric patients to determine the potential for acceptance as a standard approach in this population .\nfollowing irb approval , 150 charts of patients who underwent nissen procedures from 1994 to 2005 were divided into 3 treatment groups defined by technical approach , either robotic ( r ) ( n=50 ) , laparoscopic ( l ) ( n=50 ) , or open ( o ) ( n=50 ) .\ngroups were case - matched and performed by several surgeons and residents , under the care of one of the 3 staff surgeons at our facility .\nthe robot system used was the da vinci ( intuitive surgical , mountain view , ca , usa ) .\nthe fourth arm was used in a minority of pediatric patients due to the short distance between ports leading to the restricted movement of the working arms outside the patient .\nwe now use a 5-mm scope in addition to the 11-mm stereoscopic scope more typically used .\nall cases were performed with the patient in a reverse trendelenburg position under general anesthesia and complete paralysis with an age - appropriate esophageal dilator in place .\nport placement with the robot followed laparoscopic standards with the exception of ports being placed more distant to one another to allow broader external movements .\nin open cases , unless the patient had a previous midline scar , a left subcostal incision was performed .\nregardless of the surgical approach , once the equipment was inside the abdominal cavity , identical steps were taken to dissect the gastroesophageal junction and wrap the gastric fundus around the esophagus .\ndescriptive and analytical statistics were applied to compare surgical times , length of hospitalization , and outcomes using kruskal - wallis and tukey tests for continuous data and the chi - square text for nominal data .\nin the 150 nissen cases included in this study , patients were younger and smaller in the open group ( 8555 months , 2417 kg , p<0.05 ) compared with those in the robotic ( 11764 months , 3723 kg ) and laparoscopic groups ( 10771 months , 3324 kg ) ( table 1 ) .\nthe most common indication for the procedure was reflux refractory to medical management either as the sole reason or associated with failure to thrive or neurological impairment , or both of these [ r = 39(78% ) , l = 50(100% ) , o = 34(68% ) ] .\nother indications include a failed previous antireflux procedure , reflux associated with oromotor dysfunction , hiatal hernias , aspiration with an acute life - threatening event , and esophageal stricture .\nrobot operative times proved significantly longer compared with times for laparoscopic and open procedures ( r 16061 min , l = 107 + 31 min , o = 7327 min , p<0.05 ) .\nthe number of gastrostomy tubes done in addition to the nissen fundoplication in the robot group were similar to that of the other groups [ r = 17/50 ( 34% ) , l = 24/50 ( 48% ) , o = 11/50 ( 22% ) , p>0.05 ] .\nthe robot group experienced 2 conversions to the open approach ( 2/50 4% ) , comparable to the laparoscopic conversion rate ( 1/50 2% ) .\nopen cases resulted in longer hospitalization compared with the robot - assisted cases [ r = 2.944.5 d , o = 3.52.8 , p<0.05 ] .\ncomplication rates were equivalent between groups , including hiatal hernia , tight wrap requiring dilatation , and wound infection [ r = 7(14% ) , l = 8(16% ) , o = 5(10% ) , p=0.387 ] . the most common complication with the da vinci and laparoscopic approaches was a tight wrap , requiring dilatation [ r = 4/50 , 8% and l = 3/50 , 6% ] , whereas in the open series , wound infections were more common ( 2/50 , 4% ) . on 30-day follow - up ,\nthe presence of transient symptoms including dysphagia , abdominal pain , feeding aversion , and gas bloating were equivalent [ r = 15 ( 30% ) , l = 14(28% ) , o = 6(12% ) , p=0.06 ] .\nin our experience , the robot proved to be an acceptable approach for laparoscopic nissen fundoplication .\nthis parallels the findings reported on early experiences from other centers . as in previous randomized trials , our experience with nissen fundoplication shows comparable efficacy of the robotic and laparoscopic approaches , with similar morbidity . the laparoscopic procedure , whether da vinci assisted or not , demonstrated a slight reduction in hospital stay compared with the open technique .\npatient demographics , surgical times , and complication rates according to surgical approach denotes significant difference between the robot vs. open group .\nof the 2 robot cases that were converted to open , one was due to intraoperative hypotension and arrhythmia and the other due to difficult dissection following failed prior repair .\npostoperatively , the presence of transient symptoms was similar between groups , reaching up to 30% .\nthere was a trend towards fewer symptoms in the open group that may be due to achieving a tighter wrap in the robot and laparoscopic groups leading to more gas bloating and abdominal complaints .\nhowever , in long - term follow - up , all patients achieved symptomatic relief .\nthe learning curve for the da vinci system played a key role in our surgical times despite previous reports .\nthe 50 robotic cases in our study were distributed among the 3 surgical faculty and 4 pediatric surgery residents during this time .\nin addition to this , the robot requires several extra steps to achieve assembly in a sterile fashion and to change the instruments .\nwe believe these factors combined would explain why the robot - assisted procedures resulted in both longer operative and total room times compared with the open series .\nwe expect reduced surgical times once the operating surgeons overcome this 10-case learning curve and reduced setup time as well with more practice and repetition of use . therefore , like others , we have found no proven outcome benefits of using the robot in low- or medium - difficulty cases compared with the laparoscopic approach .\npotential benefits over standard laparoscopy include 3-dimensional image quality , camera steadiness , and the dexterity of the instrumentation for dissection and suturing .\nto better delineate cases that benefit most from each one of the 3 techniques , randomized prospective trials utilizing surgeons past the learning curve is required .\nrobot - assisted surgery is equivalent to standard laparoscopic surgery in terms of complications and length of stay , with both having significantly increased operation times but reduced length of stay compared with open surgery .\nimproved results are expected once the learning curve is overcome . however , potential outcome benefits have yet to be proven .", "answer": "background : robot - assisted surgery must be evaluated before its acceptance as an option for standard therapy in the pediatric population . \n our objective is a comparison of results using the robot system with results for the laparoscopic and open approaches.methods:following irb approval , robot - assisted procedures were case - matched with controls , selected from 1994 to 2005 . \n data for 150 nissen cases were divided equally into 3 groups [ robot ( r ) , laparoscopic ( l ) , and open ( o ) ] , comparing surgical times , length of hospitalization , and outcomes.results:the average age ( r = 11764 months , l = 10771 months , o = 8555 months , p<0.05 ) and weight ( r = 3723 kg , l = 3324 kg , o = 2417 kg , p<0.05 ) of the open group were lower comparatively . \n robot operative times proved significantly longer compared with laparoscopic and open time ( r = 16061 min , l = 107 + 31 min , o = 7327 min , p<0.05 ) . \n the robot had 2 conversions ( 2/50 , 4% ) , comparable to the laparoscopic conversion rate ( 1/50 , 2% ) . \n open cases resulted in longer hospitalization [ r = 2.944.5 days , l = 3.547.8 days , o = 3.52.8 , p<0.05 ] . \n complication rates were equivalent between groups . \n the most common complication with the da vinci and laparoscopic approaches was tight wrap requiring dilation [ r = 4/50 ( 8% ) and l = 3/50 ( 6%)].conclusion : robot - assisted surgery is equivalent to standard laparoscopic surgery in terms of complications and length of stay , with both having significantly increased operation times but reduced length of stay compared with open surgery . \n further experience with this technology is needed to overcome the learning curve and reduce operative times .", "id": 331} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncannabis is a prominent political , health , and law enforcement issue in north america that is currently receiving a great deal of attention .\nas we watch the effects of the legalization of cannabis in colorado , washington , alaska , oregon , and the district of columbia , other jurisdictions are debating the future of this illicit drug .\nhow can we prevent commercialization promoting increased rates of use within a legalization model ? where does marijuana for medical purposes fit into the picture , if at all ?\na critical piece of information often missing from these debates or not addressed adequately is the scientific evidence about the effects of cannabis use on a person 's overall health .\nthis concern is even more pressing when it comes to the cognitive , physical , and mental health harms to adolescents who use cannabis .\nit is critical we ask these questions because adolescence is a time of rapid development that helps lay the foundation for success later in life .\nconversely , it can also set the stage for experiencing challenges in adulthood , as youth are disproportionately more likely than adults to experience greater harms from drug use .\ntheir brains are undergoing rapid and extensive development that can be negatively affected by cannabis use .\nthere is certainly cause for concern about the amount and frequency of cannabis use among youth . according to the 2014 monitoring the future ( mtf ) survey in the us , 35.1% of high school seniors reported pastyear use of cannabis , with 5.8% reporting daily or near daily use .\ncomparable prevalence rates are reported in canada , with 22% of 1519yearolds and 26% of 2024yearolds reporting pastyear use of cannabis in 2013 according to the canadian tobacco , alcohol and drugs survey . moreover\n, a 2013 unicef report noted that canada 's youth are the highest users of cannabis when compared to students in other developed countries .\nthe mtf survey also indicates a growing perception among young people that cannabis is a relatively harmless drug , and there is strong evidence that perception of harm is inversely related to rates of use . knowing that youth are disproportionately heavy users of cannabis\n, what specific concerns should this raise about short and longterm consequences and how do we incorporate these concerns in the debate ?\nrecent evidence shows that early and frequent use of cannabis has been linked with deficits in shortterm cognitive functioning , reduced iq , impaired school performance , and increased risk of leaving school early all of which can have significant consequences on a young person 's life trajectory.1 of note , the impact of cannabis use on iq has been the topic of recent debate among experts in the field and further research aimed at understanding this relationship will provide much needed clarity .\nheavy cannabis use in adolescence is also a risk factor for psychosis , a risk that is heightened if users have a preexisting vulnerability to that condition.1 cannabis use can also lead to dependence , with evidence from longitudinal studies in the us estimating the risk of developing cannabis dependence to be one in six among those users who initiated in adolescence,2 a rate higher than that reported among adults .\nrecent data from the 2012 canadian community health survey reveal that more than one in 20 young canadians aged 1524 met the criteria for cannabis abuse or dependence during the past year . there is also growing evidence from the human literature that early and frequent use of cannabis can alter structural aspects of the developing brain , including those that are responsible for memory , decisionmaking , and executive functioning.1 however , we do not yet know the full extent of the impact of early cannabis use on changes in brain function and behavior of young people , which underscores the need for further investment in research in this area . beyond longerterm consequences , cannabis can also acutely impair cognitive and motor functions like perception , coordination , and balance for hours after use .\nthis impairment presents a safety hazard for drivers getting behind the wheel , as well as for other motorists and pedestrians .\nin fact , the risk of car crashes doubles for drivers who get behind the wheel after using cannabis and this risk is further elevated if cannabis use is combined with other substances , most notably alcohol .\nrecent data from the national fatality database indicate that cannabis was the most common illicit drug present among fatally injured drivers aged 1524 in canada between 2000 and 2010 .\nthe drug abuse warning network , which monitors the health impact of drugs in the us , estimated that in 2011 , there were nearly 456,000 drugrelated emergency department visits in which cannabis use was mentioned in the medical record .\ndata from the canadian institute for health information reveal that from 2006 to 2011 , youth aged 1524 spent the largest number of days in a hospital for a primary diagnosis of mental and behavioral disorders due to the use of cannabinoids . furthermore , the number of days spent in a hospital increased by almost 40% during the same time period.3 \n these findings are particularly troubling because recent research from canada has revealed that young people are confused about cannabis and do not have the knowledge they need about the risks associated with this drug to make more informed decisions.4 some have expressed questionable beliefs about the effects of cannabis , indicating that it helps to improve their focus at school and can prevent or even cure cancer .\nyouth also expressed mixed beliefs as to whether cannabis improves or impairs driving performance , and felt that cannabis and driving was not as dangerous as drunk driving .\nyouth talked about how cannabis is natural and so they did not really think of it as a drug .\nthe findings from this reviewed research highlight the complexity of the issues surrounding youth consumption of cannabis . youth are confused with the mixed messages they are receiving from discussions ranging from legalization to the use of cannabis for medical purposes , which points to the need for a coordinated , comprehensive , factual , and consistent approach to increasing awareness of this drug and its impact .\nas primary care is an important intervention point for youth experiencing harms related to cannabis , there is an urgent need to develop practical , evidenceinformed tools to assist healthcare providers in the early identification of cannabis use and cannabis dependence , as well as tools to deliver interventions to treat potential problems .\nexamples of such tools may include screening instruments to screen for cannabis use that warrants clinical intervention , as well as brief intervention strategies aimed at addressing the problematic substance use revealed during the screening process .\nthere is also an urgent need for further research aimed at improving the understanding of differences between the short and longterm effects of cannabis use , particularly on the developing adolescent brain .\nsuch research should include mechanistic studies regarding alteration of cellular structure and function related to cannabis to determine the impact on adolescent brain development .\nof particular concern are the impacts of the dramatic increase in concentrations of tetrahydrocannabinol ( thc ) , the main psychoactive ingredient of the cannabis plant , over the past 25 years .\nthe average potency of federally seized cannabis in the us has steadily increased from 3.5% in 1985 to 13.2% in 2012.5 in light of such an increase in potency , some historical findings about the health and developmental effects of cannabis use might not be relevant when trying to predict effects on contemporary users .\nmore research is also needed to shed light on the influence of cannabis policy on public health , public safety , and other outcomes .\nthe current understanding of the impact of cannabis policy on market forces , such as healthcare costs , lost productivity costs , and tax revenues , for example , is very limited , as is overall understanding of how perception , use , and outcomes interrelate around this drug . in an effort to help clear the smoke , the canadian centre on substance abuse is currently undertaking a comprehensive review and synthesis of the literature on the effects of cannabis use during adolescence that will highlight key areas for action in policy , practice , and research\n. this muchneeded work will provide clarity to misperceptions about cannabis , and make sense of some conflicting evidence about the effects of cannabis use and the impact of early or regular use during a time when the brain is still developing . by integrating neuroscience with the behavioral and social context of cannabis use by youth\n, this report will provide a muchneeded resource for those working with youth and those involved in making decisions about policies , programs , or practices related to cannabis .\naj porathwaller has provided expert testimony at the standing committee on health 's ( hesa ) recent report on marijuana 's health risks and harms , october 2014 .", "answer": "cannabis is the most commonly used illicit substance among youth . \n recent policy developments and ongoing debate related to this drug underscore the urgent need to clear the smoke and better understand what the scientific evidence says about the health and behavioral effects of cannabis use , particularly on youth whose brains are undergoing rapid and extensive development .", "id": 332} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nseizures are the most common neurological events of childhood with approximately 35% of children experiencing a seizure at some point in their lives 25% of whom subsequently go on to develop epilepsy .\nthe prevalence of epilepsy in india is 4.9 to 6.2 per 1000 population . of these patients with epilepsy , 43%\ncomprises of children and adolescents . intractable epilepsy is defined as a failure to respond to at least two antiepileptic drugs ( aeds ) given over at least a two - year period . a single definition for intractable\n epilepsy can not suit all situations as definitions of intractability are individualized to the patient . of these patients\ndeemed to be intractable , approximately 50% are estimated to have surgically remediable epilepsy [ 4 , 5 ] .\n hemispheric epilepsy ( he ) refers to epileptiform activity in all four lobes of one hemisphere , and when it involves more than two lobes of the brain , it is termed subhemispheric epilepsy ( she ) [ 4 , 6 , 7 ] .\nthese hemispheric brain lesions are commonly associated with early onset of catastrophic epilepsies and multiple seizure types that inhibit brain development .\nthese respond well to early hemispheric / subhemispheric disconnective / resective surgeries [ 69 ] .\nan analysis was done of the pre- and postsurgical data of 34 children who underwent disconnective epilepsy surgeries , that is , a peri - insular hemispherotomy ( pih ) or a peri - insular posterior quadrantectomy ( pipq ) for hemispheric / subhemispheric epilepsy from april 2000 to march 2011 .\nthe hemisphere contralateral to the hemiparesis was shown by radiological ( mri / computerised tomography ( ct ) ) and functional ( scalp eeg / eeg video telemetry ) imaging to have a unilateral diffuse abnormality and the remaining hemisphere was normal . when the epileptogenic zone encompassed large areas of the temporal , parietal and occipital lobes with sparing of the frontal lobe\nthe decision was dependant on good concordance between the imaging ( mri , ct , nuclear studies ) , eeg , clinical and neuropsychological evaluations , and a clear localization of the lesion to the unilateral - affected region .\nthe indications for pipq were the same as for hemispheric epilepsy , the pathology being localized to involve the temporal , parietal , and occipital lobes .\nthe presence of residual voluntary motor function of the contralateral distal musculature , that is , finger opposition and foot tapping , was the indication for pipq preserving eloquent uninvolved sensorimotor cortex .\nall patients went through a presurgical evaluation including a study of the seizure semiology , neurological examination , multiple electroencephalogram ( eeg ) examinations ( video telemetry ) , magnetic resonance imaging ( mri ) , and neuropsychological evaluation .\nthe focus of the evaluation was to identify a surgically remediable epilepsy syndrome with good electro - clinico - radiological concordance .\nif the structural lesion responsible for epilepsy could be safely removed without causing deterioration in the functional status , the patient was considered for epilepsy surgery . however , if there was no concordance in investigations in the phase i evaluation , the patient would enter a phase ii evaluation which would include prolonged invasive eeg monitoring , nuclear medicine studies ( positron emission tomography ( pet ) and single photon emission computerized tomography ( spect ) ) , and a wada ( sodium amylobarbital ) test . however , none of our patients required a phase ii evaluation .\n( figure 1 ) this is a surgical method of functional hemispherectomy that enables disconnection of the hemisphere through peri - insular windows requiring limited removal of the fronto - parieto - temporal opercular cortices . following the surgical principles of anatomical subtotal removal of the hemisphere and complete disconnection ,\n the pih is a radical hemispheric tractotomy based on the concept of maximum disconnection with minimal excision .\nit resulted from the demonstration that the hemisphere could be disconnected , made nonfunctional , through very small removal of brain tissue [ 9 , 14 , 15 ] .\na pipq was performed in all cases of subhemispheric epilepsy and the surgery tailored to encompass the whole epileptogenic lesion yet preserving the central region , which is still functional .\n( figure 2 ) in this technical variant , there is a minimal removal of brain tissue but complete disconnection of the remaining major part of the abnormal cortex , which is left anatomically intact and viable by preservation of the arteries and veins irrigating these lobes . the primary motor and sensory cortices\nare identified and recognized from the study of the mri and correlation with intraoperative surface anatomy , based on gyral pattern , arteries , and veins [ 6 , 7 ] .\nthe identification of the functional cortex is also aided by electrophysiological means under general anaesthesia before the disconnection .\nthis identification maximizes both the extent of resection and the safety of surgery [ 6 , 7 ] . in this variant\n, the mesial temporal structures are resected , but the temporal neocortex is disconnected and not resected followed by a parieto - occipital disconnection [ 6 , 7 ] .\nthe data was analyzed with nonparametric tests because of the small sample size among the children with poor outcome following surgery ( engel 's class ii \nnonparametric square test and mann - whitney u test was were to compare the categorical and continuous variables between the groups .\np < 0.05 ( two tailed ) was considered significant and data was analyzed using spss ( version 19 ) .\nthe mean age of seizure onset was 3.8 years ( range : from neonates to 12 years ) .\nthe mean duration of epilepsy was 4 years ( range : from 3 months to 14 years ) .\n28 children ( 82.3% ) had a seizure frequency of 2 episodes / day , while 11 ( 32.3% ) had at least one episode of status epilepticus prior to surgery .\nepilepsy was due to rasmussen 's encephalitis ( re ; n = 11 ) ( figure 3 ) , infantile hemiplegia seizure syndrome ( ihss ; n = 12 ) ( figure 4 ) , hemimegalencephaly ( hm ; n = 3 ) ( figure 5 ) , sturge weber syndrome ( sws ; n = 4 ) ( figure 6 ) , and postencephalitic sequelae ( pes ; n\ntwenty - seven ( 79.4% ) patients underwent pih for lesions causing hemispheric epilepsy , and seven ( 20.6% ) underwent pipq for lesions causing subhemispheric epilepsy .\nthe seizure outcome after surgery was assessed by engel 's classification and is described along with followup in table 1 .\nwe recorded 11 variables and analyzed them to arrive at predictive variables of a complete seizure freedom .\nwe found that age of seizure onset ( p = 0.03 ) and the etiology of the disease causing epilepsy ( p = 0.007 ) were predictive variables for the same .\npatients who had re , sws , pes , and ihss had good seizure outcomes following surgery .\nthe results of our cognitive outcomes that have been published before show that the mental and social age showed a steady increase after surgery .\nhowever , in the long term , intelligence quotient ( iq ) showed only a gradual gain on followup .\nolder age of onset of seizures and a shorter duration of seizures prior to surgery were predictive of positive cognitive gains following surgery .\ncomplications in this series included pseudomeningocele in 2 ( 5.8% ) and low pressure hydrocephalus in 1 ( 2.9% ) who required a low pressure ventriculoperitoneal shunt .\nthis is quite low as compared to other published series ( table 4 ) [ 911 ] .\nwe also had 15 patients who developed postoperative fever , but csf cultures were sterile .\nthis could have been due to an aseptic meningitis due to the presence of blood products in the disconnected cavity .\nour series documents 91.1% seizure freedom , which is similar to other published studies [ 9 , 12 , 1621 ] . following functional hemispherectomy ,\nseizure free outcomes have ranged from 52 to 90% [ 9 , 1621 ] . this range could be explained by differences in patient selection or technical pitfalls such as incomplete removal in anatomical hemispherectomy and incomplete disconnection in functional hemispherotomy [ 14 , 19 ] .\nwe found the age of seizure onset to be a strong predictor of seizure freedom ( table 2 ) .\nthis finding is also supported by other studies [ 3 , 22 , 23 ] .\na younger age of seizure onset is usually seen in children with developmental cortical malformations and multifocal epilepsy , which are proven to have poor seizure control .\nthe etiology of the disease producing epilepsy is also a strong predictor of seizure freedom ( table 3 ) .\nthe best results in our series were obtained in children suffering from re , sws , pes , and ihss ( table 3 ) .\nihss and sws are seen in the perinatal age group , and they are generally unilateral with complete sparing of the opposite side . there has been evidence to support that in such cases , early surgical intervention facilitates good seizure control and helps the uninvolved hemisphere to develop and take over the functions of both sides\n. however , in one patient with ihss , we had a class ii seizure outcome and this was in the initial part of the series , which could be attributed to incomplete disconnection , and this patient was lost to follow up .\nall patients with re had a class i seizure outcome as this disease also strictly affects only one hemisphere . however ,\nthe seizure outcome in patients with hm was not satisfactory as described in literature , and this has been reported in other series too [ 9 , 1721 ] .\nthe likely explanation could be the presence of migrational abnormalities in the so - called preserved hemisphere or early development of an epileptic encephalopathy , already in utero .\nwe found a significant gain in the mental and social age in the immediate postsurgical period which continued into the second and third years of followup .\nour study also showed that older age of onset of seizures showed positive mental and social age gains at followup .\nonset of intractable epilepsy within the first 24 months of life is a significant risk factor for mental retardation , especially if seizures occur daily [ 12 , 24 ] .\nmost of these children have a low dq / iq to begin with and the improvement in cognitive skills after surgery is poorer in these children .\nfurthermore , our study also showed that a shorter duration of seizures prior to surgery is predictive of positive mental and social age gains , a finding that is in keeping with those of freitag and tuxhorn and basheer et al . .\nin general , children with ie in our country are not exposed adequately to environmental stimuli as schooling is discontinued in the presence of seizures . with good postoperative seizure control ,\nthe child 's attention capacities increase and they engage in social interaction with their family and peers .\nan improved school attendance due to seizure freedom improves their adaptive skills that in turn helps the child improve his performance in activities of daily living .\nin our experience , over 90% of children with hemispheric and subhemispheric epilepsy syndromes achieve an excellent seizure outcome with less morbidity following epilepsy surgery . age of seizure onset and etiology of the disease causing epilepsy are independent predictive variables of a good seizure outcome .\nfollowing seizure freedom , improvement of function in the residual brain occurs that in turn leads to improvement in adaptive and social functions and quality of life .", "answer": "objectives : to study the outcome of disconnective epilepsy surgery for intractable hemispheric and sub - hemispheric pediatric epilepsy . \n methods : a retrospective analysis of the epilepsy surgery database was done in all children ( age < 18 years ) who underwent a peri - insular hemispherotomy ( pih ) or a peri - insular posterior quadrantectomy ( pipq ) from april 2000 to march 2011 . \n all patients underwent a detailed pre surgical evaluation . \n seizure outcome was assessed by the engel 's classification and cognitive skills by appropriate measures of intelligence that were repeated annually . \n results : there were 34 patients in all . \n epilepsy was due to rasmussen 's encephalitis ( re ) , infantile hemiplegia seizure syndrome ( ihss ) , hemimegalencephaly ( hm ) , sturge weber syndrome ( sws ) and due to post encephalitic sequelae ( pes ) . \n twenty seven ( 79.4% ) patients underwent pih and seven ( 20.6% ) underwent pipq . \n the mean follow up was 30.5 months . at the last follow up , 31 ( 91.1% ) were seizure free . \n the age of seizure onset and etiology of the disease causing epilepsy were predictors of a class i seizure outcome . \n conclusions : there is an excellent seizure outcome following disconnective epilepsy surgery for intractable hemispheric and subhemispheric pediatric epilepsy . an older age of seizure onset , re , \n sws and pes were good predictors of a class i seizure outcome .", "id": 333} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthyroid lesions containing gross fat include heterotopic fat nests , thyrolipoma , teratoma , liposarcoma , and thyroid cancers of the papillary or follicular type ( 234567 ) .\nmost of these cases are only described upon obtaining pathological data after surgery ; radiologic methods are of limited use ( 89 ) . with the approval of the institutional review board of our hospital ,\nwe reported the case of an intrathyroid nodule composed mainly of gross fat detected by computed tomography ( ct ) and confirmed by lobectomy as a follicular variant of papillary thyroid cancer ( fvptc ) with mature fat .\na 58-year - old woman presented with an incidentally detected mass in the thyroid on routine ultrasonography ( us ) at a primary clinic .\nthe patient had a 10-year history of diabetes mellitus and hypertension , and was currently taking medication .\nphysical examination revealed a firm mass of approximately 3 cm in size in the right anterior neck .\nlaboratory tests revealed that serum anti - microsomal antibody , anti - thyroglobulin antibody , thyroglobulin , calcitonin , t3 , free t4 , and thyroid - stimulating hormone levels were within normal ranges .\nultrasonography revealed an ovoid lesion with a smooth margin of approximately 2.9 2 1.3 cm in size .\nthe nodule was generally hyperechoic , with the peripheral portion more hyperechoic than the central area .\nthe perithyroidal fat , muscle , and vertebral bodies were therefore not clearly visualized ( fig .\ndoppler us did not show any vascular signals in the nodule . based on these findings\na board - certified radiologist performed us - guided fine needle aspiration using a freehand technique with a 23-gauge needle and a 5-ml disposable plastic syringe .\ncytologic smears were made on glass slides and immediately fixed in 95% alcohol for both papanicolaou staining and may - grunwald - giemsa staining .\ncytology revealed atypia of undetermined significance or a follicular lesion of undetermined significance with negative for braf mutations and positive for an nras 61 mutation .\nthe thyroid ct protocol at our hospital includes pre - contrast , early , and delayed phases .\nearly phase images ( 40 seconds ) were scanned from the hyoid bone to the thoracic inlet to cover the entire thyroid and level iii - vi lymph nodes .\ndelayed scans ( 90 seconds ) covered the area from the skull base to the upper mediastinum .\nall scans were acquired with a slice thickness of 2.5 mm and reconstruction increment of 2.5 mm .\npre - contrast ct showed markedly low attenuation ( mean ct number , -80 hounsfield units [ hu ] ) , in a well - defined mass with fine reticular and thick septa - like structures in the parenchyma of the right mid - to - upper portion of the thyroid ( fig .\n1b ) . to measure the enhancement pattern of the tumor , 25 mm of the region of interest was placed in the area of the fatty mass , including the reticular and thick septa - like soft tissue lesions .\nthe tumor was enhanced in the early phase ( mean ct number , 16 hu ) and was washed out in the delayed phase ( mean ct number , -13 hu ) ( fig .\nthe tumor was ovoid in the longitudinal direction , had a lobular appearance in the axial plane , and was completely encapsulated in the thyroid parenchyma , with no evidence of extrathyroidal extension .\nbased on these findings , we suspected a fat - containing , neoplastic lesion of the thyroid gland , such as thyrolipoma , teratoma , lipoma , low - grade liposarcoma , or a follicular tumor with stromal fat . considering the results from cytopathology and the gene mutation analysis\nit showed a yellowish , homogeneous , and well - demarcated nodular lesion measuring 2.5 2.2 1.5 cm at the upper - to - mid pole .\nmicroscopic examination revealed a well - circumscribed , thin , fibrous , and capsulated nodule with mature fat .\nthere were atypical follicular cells with nuclear enlargement , nuclear overlapping , chromatin clearing , and nuclear grooves without papillary structures in the nodule ( fig .\non immunohistochemistry , the tumor cells stained positive for hbme-1 ( dako , glostrup , denmark , 1:100 ) and galectin-3 ( novocastra , newcastle upon tyne , uk , 1:200 ) . finally , we tested for the v600e and k601e mutations in exon 15 of the braf gene and codons 12 , 13 , and 61 of the kras and nras genes .\nin our case , the tumor was a yellowish , homogeneous , and well - demarcated nodular lesion on gross examination , with negative value of attenuation on ct , suggesting fat .\nhowever , it was difficult to recognize the tumor as a fat containing mass on us examination .\nthe hyperechoic nature of the mass and the curtain - like hyperechoic shadowing posterior to the mass may suggest rich fatty component .\nwe suspected that the hyperechoic shadowing might have been due to a reverberating artifact caused by innumerable fat globules and septa of the tumor , similar to the artifact frequently observed along the thick abdominal walls that consist of several layers of fat globules surrounded by connective tissues , skin , and fascia . computed tomography and gross specimen findings of our case were very similar to those of thyrolipoma , a benign fat - containing tumor ( 810 ) .\nthyrolipoma is considered a variant of follicular adenoma , which is characterized by a well - circumscribed and encapsulated nodule resulting from the proliferation of thyroid follicles admixed with mature fat ( 1011 ) .\nthis case could have been misdiagnosed as a follicular neoplasm or thyrolipoma , as the tumor cells did not show a papillary growth pattern upon microscopic examination and the gross features were very similar to thyrolipoma .\ntwo reports provided the ct and magnetic resonance imaging findings of thyrolipoma ( 812 ) .\nthe mass predominantly had fat attenuation and distinct margins in the thyroid gland . however , the authors only performed pre - contrast ct on the lesion .\ntherefore , it is uncertain whether thyrolipoma and thyroid cancer with massive stromal fat can be differentiated by ct with contrast enhancement . in our case ,\nthe tumor was enhanced in the early phase and slightly washed out in the delayed phase .\nfat - containing thyroid cancer of the papillary or follicular type , have only been reported from pathological studies ( 2456 ) .\nfat tissue was observed only by microscopy , so it was assumed that small amounts of fat tissue could not be detected by ct .\nwe also assumed that the detectability of the fat component is variable , as it depends on the total number of fat cells in the mass .\nmature teratoma can be recognized if the fat - containing mass contains calcification , bone or cartilage , and cystic components .\nhowever , this is not possible , as radiological images do not always exhibit all these attributes ( 7 ) .\nct images of liposarcoma ( 3 ) in the thyroid gland are very similar to those in our case , and differentiating between teratoma , thyrolipoma , liposarcoma , and papillary thyroid cancer with massive fat may be impossible using radiology alone .\nsome investigators have insisted that fat cells are derived from displaced remnants of embryonic structures in the thyroid . in amyloid goiter ,\nschrder and bcker ( 1 ) postulated that adipose tissue may be derived from metaplasia of stromal fibroblasts due to either impaired circulation and diffusion or tissue hypoxia caused by amyloid deposition .\nderienzo and truong ( 5 ) suggested that the fat cells in thyrolipoma and follicular carcinoma might be neoplastic tissue because 1 ) fat did not exist in the normal thyroid , 2 ) fat was a major component of the tumor , 3 ) there was no evidence of degenerative changes such as dystrophic calcification , cystic or hemorrhagic degeneration , or amyloid deposition , 4 ) fat was widely distributed in the tumor , and 5 ) there were similar fat - containing tumors in other organs such as thymolipoma , parathyroid adenoma , and fat - containing fibroadenoma of the breast .\nour case showed similar microscopic features to theirs in agreement with the suggestion that the fat cells might be neoplastic cells themselves . in summary\nthese findings included a hyperechoic mass with a smooth margin with a reverberating artifact and no detectable doppler signal on us .\nct revealed a well - encapsulated fat - attenuation mass with enhancing septa - like structures .\nfvptc should be included in the differential diagnosis of fat - containing focal lesions in the thyroid , in addition to thyrolipoma , teratoma , liposarcoma , and small focal fat nests near the capsule .\nmoreover , fine needle aspiration cytology with gene analysis may be helpful in determining the nature of fatty tumors before surgery .", "answer": "thyroid cancer may have small adipose structures detected by microscopy . however , there are no reports of thyroid cancer with gross fat evaluated by radiological methods . \n we reported a case of a 58-year - old woman with a fat containing thyroid mass . \n the mass was hyperechoic and ovoid in shape with a smooth margin on ultrasonography . \n on computed tomography , the mass had markedly low attenuation suggestive of fat , and fine reticular and thick septa - like structures . \n the patient underwent a right lobectomy . \n the mass was finally diagnosed as a follicular variant of papillary thyroid cancer with massive stromal fat .", "id": 334} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncleft lip and palate ( clp ) is one of the most common craniofacial anomalies of humans .\nvaried incidence of clp deformity caused due to unknown precise etiology is reported in the literature with severity ranging from minor notching of lip or bifid uvula to complete unilateral or bilateral cleft of the lip and palate .\nnewborns with abnormal oro - nasal communication face the threat to life due to difficulty in feeding . hence , there arises an acute demand of feeding appliance that serves as an obturator in the cleft area , in view of the complications of feeding tube .\na feeding appliance or obturator is a prosthetic aid that is used to restore the separation between oral and nasal cavities .\nin addition , it is also the primary step in the fabrication of different devices such as palatal obturator , articulation development prosthesis , palatopharyngeal obturator , palatal lift prosthesis , nasal conformer , and appliances for presurgical infant orthopedic or presurgical nasoalveolar molding , those that are introduced to enhance speech , esthetics , and function .\nit has been emphasized in literature that every precaution must be taken while making impression for neonates and infants with cleft palate , and surgeons ' presence is needed to manage airway emergency .\nmaneuvering the child 's head position forward to avoid the aspiration of impression material has been the only suggested precaution .\nthis does not ensure complete control over the impression material and avoidance of complication of impression material being pushed too deep into the nasal cavity or distally through the pharynx .\nthis clinical report presents dental putty - gauge hybrid impression technique as a simple and safe method of maxillary impression making in neonates and infants with cleft palate , permitting complete control over impression material during functional movements .\non extraoral examination , there was bilateral complete cleft lip with forward placed premaxilla [ figure 1 ] .\nintraoral examination revealed a median cleft of the palate involving complete soft and hard palate [ figure 2 ] .\nthey were explained the treatment plan for fabrication of feeding plate and consent was obtained .\nextraoral view showing bilateral cleft lip intraoral view showing cleft lip and palate it was planned to make the maxillary impression when the infant was fully awake , without any premedication or anesthesia .\nthe infant was seated upright in his mother 's lap in dental chair with face forward .\nsmall size of the mouth opening did not permit the use of impression tray or flat wooden stick as carrier for the material . thus , it was planned to make impression with finger - loaded impression material . fast setting elastomeric putty impression material ( express std ,\n3 m espe , usa ) was mixed and loaded on the index finger and an adequately large piece of gauze was wrapped all over the loaded impression material with loose ends wrapped toward the hand [ figures 3 and 4 ] .\nthe gauze permitted control over the material and restricted the excessive displacement of impression material toward the nasal cavity and pharynx [ figure 5 ] .\nthick consistency of the impression material did not permit leakage of material through the gauze and kept it within the flexible confines of the gauze .\nthe resultant sucking pressure embedded the gauze threads in the putty impression material as the easily moldable gauge did not offer any resistance .\nafter the impression material was set , the impression was removed in toto from the patient 's mouth [ figures 6 and 7 ] .\nthen , the impression was poured in dental stone ( kalstone , kalabhai karson pvt ltd ) .\n, mumbai , maharashtra , india ) and the master cast was obtained [ figure 8 ] .\nsingle visit feeding obturator was fabricated using clear , flexible thermal - forming material with a midline extraoral extension for a hole to tie a safety thread [ figure 9 ] .\ndental putty loaded on the index finger gauze wrapped around the putty impression material loaded on the finger maxillary impression made with functional movements by neonate hybrid impression retrieved in toto dental putty maxillary impression clear soft feeding obturator with safety thread attached feeding obturator in situ parents were demonstrated about the use and hygiene maintenance of the feeding plate .\na regular follow - up after 24 h and monthly follow - ups later were scheduled and the parents were advised to use the appliance till surgical intervention .\na cleft palate hampers intraoral pressure built - up required for suction and favors nasal reflex of food , thus posing challenge of middle ear infections .\nfeeding is an immediate concern for newborn with clp where the role of dentist and the feeding plate is evident .\nvarious head and body positions and diverse impression materials have been used to make maxillary impression in neonates and infants with suggestions to take all precautions including the presence of surgeon to handle airway emergency . a feeding appliance bridges the gap between oral and nasal cavities .\nfeeding obturator becomes urgent in clp infants considering the health of the infant as surgical treatment usually starts at 23 months of age .\nhowever , little is found in literature regarding the impression required to fabricate these maxillary appliances .\nimpression making is the initial , crucial , and clinical step in cleft palate of infants and poses a challenge because of lack of cooperation from patient , inadequate size of oral cavity , and nonavailability of suitable impression trays .\nthere is a risk of breakage of some parts of impression material that may get lodged in the undercut in the defect or the child can swallow or aspirate the material .\ndifficulty in withdrawal of impression , cyanotic events , and asphyxiation has been encountered during impression making\n. displaced intranasal impression material may remain undetected for a very long period of time .\nimpression compound softened and placed on finger is the commonly used method to make preliminary impression .\nindividualized impression trays for clp have been designed and the tray handle has also been used to carry the material . impression making under general anesthesia has been adopted for infants .\nadequate suctioning and resuscitation facilities should be available chairside . in case of airway emergency ,\nit is advised to maneuver the infant position and head position to keep the tongue forward to avoid posterior displacement of impression material . making the child to cry throughout the impression procedure\nhowever , it does not prevent the thin consistency material passing down the pharynx . in this case , the child was not crying during the procedure , but performed the functional movements to mold the impression material to obtain accurate anatomic details .\ncleft palate affects feeding , facial growth , dentition development , speech , and may cause psychological problems for the child and parents as acceptance of the parents for the dysmorphic child can be difficult .\nhowever , in the present case , parents were involved in the care from the start of therapy that provided assurance and motivation to them .\na variety of impression materials have been advocated ; however , putty type vinyl polysiloxane has been used in this case because its high viscosity reduces the risk of aspiration and there is no risk of thermal injury to the delicate oral mucosa of the neonate unlike that with the use of wax or thermoplastic impression compound . the use of gauze wrapped around the impression material throughout the functional movements completely removed the chances of aspiration or swallowing of material making , it a risk - free procedure in an awake child as young as 1-day - old .\nhowever , in this patient , soft , clear , and flexible thermoplastic material was used as it permitted a single - step appliance fabrication .\nthe feeding plate was delivered without any delay , on the same day in view of the urgency for feeding the newborn .\nthe prosthetic therapy delivered through feeding plate remains a suitable treatment modality until the time prenatal diagnosis and intrauterine fetal surgery through feto - endoscopic approach for human fetus with a clp are well established .\nthis article describes the successful immediate oral rehabilitation of clp neonate achieved with simple feeding appliance and risk - free procedure that decreased the stress for the parents and the child and provided instant feeding ability .\nmaxillary impression procedure in infants with cleft palate poses a unique set of challenges and we should be well - equipped for every precaution while making impression .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .", "answer": "cleft lip and palate is one of the most common craniofacial anomalies of humans . \n intraoral impression making is the first clinical step in the fabrication of feeding appliance for infants with oro - nasal communication . \n it is difficult to control the flow of the impression material in the cleft area and undercuts in a child patient . \n this clinical report presents a simple and safe impression technique for maxillary impression making in neonates and infants with cleft palate . \n a gauze piece was used to confine the impression material during functional movements of sucking while impression making in an awake child to avoid the risk of aspiration or swallowing .", "id": 335} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nuncontrolled bleeding remains major challenge , responsible for 40% trauma - related deaths , which could be prevented by timely intervention . in blunt trauma , extent of hemorrhage\ncan not be determined by physical examination , as vital signs may not give a clear picture in all the patients , especially young healthy once .\nalthough abnormal vital signs does indicate shock but the absence of abnormality does not exclude hypoperfusion in trauma patients .\ndecision - making is difficult , regarding surgical intervention to treat injuries hidden from physical examination .\nthese patients are intensely vasoconstricted and may suffer end organ ischemia even with normal systolic blood pressure ( sbp ) .\nalthough shock index ( si ) can be a useful parameter in acute hemorrhage , but it still needs more study in its support to be better than simple vital sign analysis .\nblood ammonia has been shown to be elevated in hemorrhagic shock in animals and humans .\nintestinal bacterial enzymes acting on it produces ammonia which is freely diffusible and moreover liver in not fit for detoxification of ammonia .\nwe investigated the significance of ammonia levels estimation in blunt trauma abdomen patients to predict internal hemorrhage , complications and correlated with need of intervention .\none hundred blunt trauma abdomen patients ( > 12 years old ) presented in trauma ward / emergency department of tertiary care hospital were included in the study .\ngroup i required blood transfusion 2 units and/or intervention to control bleeding within 24 h following admission .\nit was analyzed within 20 min of sampling on autoanalyser cobas 6000 ( roche diagnostics india pvt ltd ) .\nroutine investigations such as blood sugar , kidney function test , hemogram , x - ray chest , and ultrasound abdomen were done at admission .\ngroup i comprised 62 patients , forty patients needed intervention and blood transfusion both , whereas 22 patients needed only 2 units of blood .\naverage age was 31.84 14.8 and 32.37 13.6 years , respectively , almost same in both the groups .\nmost of the patients had more than one organ system involved and most frequently injured organ was liver ( 40% ) followed by spleen ( 29% ) .\nmean si and arterial ammonia levels were significantly higher in group i compared to group ii patients [ table 1 ] .\nabout 88.7% patient of group i had si > 0.9 compared to only 13.1% patients in group ii [ table 2 ] .\nsignificantly higher number of patients developed complications in group i compared to group ii ( 38 vs. 7 ) and 8% mortality rate was noted in group i only .\npatients , who developed complications or died , had higher levels of ammonia at admission [ table 3 and figure 1 ] .\nmean shock index and ammonia levels percentage of patients showing shock index 0.9/0.9 ammonia levels in patients with complications and mortality in group i receiver operating characteristic analysis of hospital stay , shock index , and ammonia levels the cutoff point for ammonia levels is > 58.85 mol / l ( sensitivity 77.42% and specificity 93.37% ) .\npositive predictive value and negative predictive value at this point are 96.7% and 78.9% , respectively .\nthe cutoff point for ammonia levels is > 58.85 mol / l ( sensitivity 77.42% and specificity 93.37% ) .\npositive predictive value and negative predictive value at this point are 96.7% and 78.9% , respectively .\nroadside accidents were a major cause of trauma ( motor vehicle injury ) in our study probably due to increase population and number of vehicles on the road . similar cause has been reported by other studies also .\na maximum number of patients ( 78% ) were below the age of 40 years suggesting this age group people are more outgoing and rash drivers making them more prone to accidents .\nmale preponderance ( 93% ) noted in our study is higher than earlier studies , may be reflecting indian culture where male member of the family being breadwinner , needs to travel more than females .\nthe routine evaluation of blunt trauma abdomen patients includes various clinical parameters , physical examination , radiological and laboratory findings .\nincreased ammonia levels as observed in our study could itself be danger signal in these patients as it is sign of blood in abdominal cavity due to blunt trauma . intestinal bacterial enzymes acting on it produces ammonia which is freely diffusible and moreover liver in not fit for its detoxification as hemorrhage decreases hepatic blood flow through portal vein causing dysoxia of cells\n. increased ammonia levels have been reported in animal hemorrhagic shock and in few human studies as well .\ncutoff value for ammonia was also calculated to maximize sensitivity and specificity in identifying patients requiring intervention .\nthe purpose of this study was to augment the diagnostic accuracy of routine clinical assessment of such patient .\nhigh ammonia levels in bleeding patients ( group i ) correlated well with si as 88.7% of these patients had si > 0.9 , i.e. , having potentially severe trauma requiring immediate treatment .\nother workers have also reported similar si in bleeding patients . although si can be useful clinical parameter in acute hemorrhage which depicts severity of situation in heterogeneous patients presented in emergency but it still needs more study in its support to be single reliable parameter .\nfive patients died in group i had high ammonia levels ( 87.4 mol / l ) at admission .\nhigh ammonia itself is toxic and can cause various complications , so it must be diagnosed and treated as early as possible .\nmoreover , trauma patient loses lots of valuable time in reaching trauma center , but once reached the hospital , they need to be diagnosed correctly and quickly .\nbiochemical marker which is time and cost effective such as ammonia estimation can predict need of intervention in these patients and best treatment can be provided in the golden hour .", "answer": "background : in blunt trauma , extent of hemorrhage can not be determined by physical examination , and vital signs may also not give clear picture in all the patients , especially young healthy ones . \n hemorrhagic shock has been reported to increase blood ammonia levels . \n arterial ammonia was analyzed in blunt trauma abdomen patients and correlated with shock index ( si ) . \n its predictive value was determined for timely decision of intervention.materials and methods : hundred blunt trauma abdomen patients presented in the emergency ward of tertiary care hospital were included in the study . \n group i comprised 62 patients requiring either blood transfusion 2 units and/or intervention to control bleeding within 24 h following admission . \n group ii had 38 patients : not requiring transfusion / intervention during hospital stay . \n arterial blood sample was taken immediately after admission ; ammonia was analyzed within 20 min of sampling on cobas 6000 ( roche ) . \n si was calculated . \n predictive value of ammonia was determined using receiver operating characteristic curve.results:ammonia levels and si were significantly ( p < 0.001 ) higher in group i compared to group ii patients ( 68.55 14.36 \n umol / l vs. 37.55 7.41 umol / l and 1.28 0.5 vs. 0.74 0.12 , respectively ) . \n significantly higher number of patients in group i ( 88.7% vs. 13% ) had si > 0.9 . \n ammonia levels were significantly higher in patients with complications and in those expired.conclusions:ammonia levels were significantly higher in patients requiring blood transfusion / intervention in 24 h of admission . \n the best cutoff value to maximize sensitivity and specificity was ammonia > 58.85 \n mol / l . \n ammonia estimation at admission can be clinically significant indicator of traumatic hemorrhage needing intervention .", "id": 336} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe conducted a preliminary screening of the 16s rrna methylase - producing bacilli on our gram - negative microbial stock of 2,877 strains isolated from japanese hospitals within the past several years .\narbekacin , a semisynthetic aminoglycoside belonging to the kanamycin group , requires 2 modifications at the ( 6 ) aminogroup and the ( 2 ) hydroxyl group for inactivation , so this agent is not inactivated by known plasmid - mediated aminoglycoside - modifying enzymes .\n512 mg / l ) was used as a marker for screening the 16s rrna methylase - producing strains .\nall arbekacin - resistant strains were subjected to polymerase chain reaction ( pcr ) analysis to detect rmta , rmtb , or arma , and all strains were pcr positive , except for a strain of acinetobacter demonstrating a very high level of resistance to arbekacin ( mic 1,024 mg / l ) .\nthis strain was later shown to produce both aminoglycoside 6-acetyltransferase and 2-adenyltransferase ( 12 ) , so arbekacin was inactivated in this strain by both 6-acetylation and 2-adenylation .\neach pcr primer set was used to detect rmta and rmtb genes as in our previous reports ( 6,7 ) .\nthe pcr primers for amplification of arma were newly designed ( forward : 5-agg ttg ttt cca ttt ctg ag-3 , reverse : 5-tct ctt cca ttc cct tct cc-3 ) , and the predicted size of the amplicon was 590 bp .\nthese 3 sets of pcr primers were very reliable in detecting rmta , rmtb , and arma genes , respectively .\neach pcr amplicon was then subjected to sequencing analyses on both strands to confirm its nucleotide sequences for detecting mutations in the methylase genes .\nas reported in our previous study , rmta and rmtb genes had been found in p. aeruginosa isolates ( 6,10 ) and in 1 strain of s. marcescens ( 7 ) , respectively . as shown in the table , 5 p. aeruginosa strains isolated after our previous report ( 6 ) were rmta positive .\nthe rmtb gene was additionally identified in 4 k. pneumoniae , 2 e. coli , and 1 k. oxytoca strains in japan . to our surprise ,\nthe arma gene , which had been found in various gram - negative microbial species belonging to the family enterobacteriaceae exclusively in europe as reported by galimand et al .\n( 13 ) , was also identified in japan in 1 strain each of e. coli , s. marcescens , and acinetobacter sp .\nnotably , the arma and rmtb genes were also recently identified in k. pneumoniae and e. coli in taiwan ( 9 ) .\nfurthermore , the genetic environment of the arma gene found in c. freundii isolated in poland was similar to that of k. pneumoniae isolated in france .\nthe genetic environments of the arma gene found in the 3 japanese microbial species , e. coli , s. marcescens , and acinetobacter sp . , ( genbank accession nos . ab116388 and ab117519 ) , were also similar to those found in europe ( genbank accession nos . af550415 and ay220558 ) .\nthese findings suggest that the arma - producing gram - negative nosocomial microbes that harbor a very similar genetic environment carrying the arma gene have spread globally .\nas described previously , arbekacin still shows a very broad antimicrobial spectrum from gram - positive to gram - negative nosocomial microbes and has been approved solely to treat methicillin - resistant staphylococcus aureus ( mrsa ) infections in japan since 1990 to ensure the prudent use of this agent .\nthe emergence and presence of the 16s rrna methylase - producing gram - negative bacilli , however , has not been well recognized in japan to date ; arbekacin has not been listed among the antimicrobial agents for daily antimicrobial susceptibility testing of gram - negative microbes .\nthe use of semisynthetic aminoglycosides , including arbekacin , in japanese clinical settings for > 10 years may have promoted the emergence and dissemination of the 16s rrna methylase - producing gram - negative microbes in japan .\nthe large amount of various aminoglycosides used in livestock - farming environments could have also been a selective pressure for the emergence and spread of pathogenic microbes that harbor genetic determinants for the newly identified 16s rrna methylases , as exemplified by recent isolation of arma - producing e. coli from swine in spain ( genbank accession no .\nsince acquisition of multidrug resistance against clinically important antimicrobial agents such as carbapenems and fluoroquinolones has been developing rapidly worldwide , the acceleration of even greater aminoglycoside resistance among gram - negative bacilli promises to become an actual clinical concern in the near future , just as vancomycin - resistant enterococci ( vre ) did in the 1990s ( 14 ) .\nthe emergence of gram - positive cocci including mrsa and vre that acquire the 16s rrna methylase could also be a grave clinical matter , although fortunately no such hazardous microbes have been identified .\nthus , steps must be taken to further block proliferation of these multidrug - resistant gram - negative super microbes , including p. aeruginosa , k. pneumoniae , and acinetobacter spp .\n, as well as multidrug - resistant cocci such as mrsa and vre , which have acquired an extraordinarily high level of resistance to various aminoglycosides through production of 16s rrna methylases , especially in clinical environments .", "answer": "emergence of the newly identified 16s rrna methylases rmta , rmtb , and arma in pathogenic gram - negative bacilli has been a growing concern . \n arma , which had been identified exclusively in europe , was also found in several gram - negative pathogenic bacilli isolated in japan , suggesting global dissemination of hazardous multiple aminoglycoside resistance genes .", "id": 337} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunlike tears and ganglion cysts of the anterior cruciate ligament ( acl ) , mucoid degeneration is a less - understood entity .\nthe injury or loss of functional synovial lining protecting the acl is the primary lesion causing mucoid degeneration of acl though there was no significant preceding trauma that patients can relate to current symptoms.1 but the symptomatology , mri findings , and arthroscopy appearance are consistent.2 the excision of the degenerated acl has been the treatment of the choice , the authors believe that if the taut and hypertrophied acl were to be debulked and notchplasty done , full extension could be achieved without having to excise the entire acl .\nthe purpose of this study was to describe the clinical characteristics and diagnosis of mucoid degeneration of the acl and to assess the outcomes of arthroscopic treatment in a series of 20 patients .\nthe mean age was 42.2 years ( range 28 - 52 years ) in males and 39.4 years ( range 30 - 54 years ) in females .\nall the patients had clinical symptoms of central knee pain behind patella without any prior trauma ( 18 patients on terminal extension and 2 patients on terminal flexion ) . in four patients , there was mean flexion deformity of 6. the type of activity performed was : physically active like running , sports , and army training ( n=6 , 30% ) ; moderately active doing routine work ( n=12 , 60% ) ; and sedentary ( n=2 , 10% ) .\nthe symptoms started insidiously , had a mean duration of 21 months ( range 1247 months ) without preceding significant trauma .\neighteen patients had extension deficit and two patients had limited flexion.34 there was medial joint pain in two patients .\nanterior lachman and anterior drawer test showed firm endpoint in all patients , with + 1 laxity in three patients .\nall patients were treated with nonsteroidal anti - inflammatory drugs and physiotherapy for a minimum of 2 months before contemplating magnetic resonance imaging ( mri ) and treatment .\nplain roentgenograph of both the knees was done with anteroposterior weight bearing , lateral and skyline views .\nradiographic diagnosis was made only when all three key criteria56 were met : ( 1 ) abnormally thickened and ill - defined acl , ( 2 ) maintenance of normal orientation and continuity , and ( 3 ) increased intraligamentous signals ( intermediate signal intensity on t1-weighted images and high signal intensity on t2-weighted and proton density weighted images [ figure 1 ] .\nproton density show increasing intraligamentous signal intensity of the anterior cruciate ligament over the left knee arthroscopy was performed by use of a 30 lens through standard anterolateral and anteromedial portals .\nall compartments were explored to evaluate the state of menisci , ligaments , and cartilage .\nthe chondral lesion of each patient was described according to the outerbridge classification.7 the locations of the lesions on the articular surfaces of the patella , trochlea , medial femoral condyle , lateral femoral condyle , medial tibial plateau , and lateral tibial plateau were recorded .\nbulk specific to anteromedial ( am)posterolateral ( pl ) bundles of acl , its color , and its tautness hooked with probe were recorded .\nimpingement of acl fibers to lateral wall of intercondylar notch , and lateral compartment during flexion extension maneuver were recorded [ figure 2 ] .\narthroscopic examination of a left knee , showing impingement ( arrow ) of hypertrophied posterolateral portion of acl to lateral wall and roof of intercondylar notch during extension the aim of surgery was to remove as much of the degenerative mass as possible without having to sacrifice the entire acl .\nthus , the remaining acl consisted of some intact anteromedial or posterolateral portion of the acl interspersed with degenerate acl tissue .\ncare was taken to see that this remaining acl had intact attachment to the femoral condyle and did not impinge on the roof or lateral wall of the notch [ figure 3 ] . by use of basket forceps ,\nthe materials were stained with h and e and then with mucoid tissue - specific alcian blue [ figure 4 ] . in knees without notch narrowing , debridement of the hypertrophied acl was performed first beginning with the removal of small osteocartilaginous fragments from the upper portion of the lateral wall and roof by use of a 6.4-mm curved osteotome .\nthis allowed easier inspection of the inner space between the acl and the lateral wall , and accurate removal of impinging structures .\nwe decompressed the lateral wall and roof from anterior to posterior while performing a flexion extension maneuver with a 4.5-mm motorized bur and curette .\ncare was taken to remove all visible impinging structures in the posterior portion of the notch .\ncopious debridement of mucoid hypertrophied lesions of the acl was performed by use of basket forceps as well as a 4.2-mm motorized shaver .\nsome of the mass was removed by first teasing between the anterior fibers of the acl using a probe and then removing it with an arthroscopy grabber .\nthe major posterior portion of the mass was removed using the basket punch ( acufex ) introduced through the anteromedial portal , with the arthroscope through the anterolateral portal .\nthe probe was used to assess the tension and the clearance of the remaining acl and the notch .\narthroscopic examination of a left knee , showing impingement of hypertrophied posterolateral portion of acl to lateral wall and roof of intercondylar notch during extension photomicrograph showing distorted collagen fibers with scanty myxomatous degeneration ( h and e stain , 40 ) during the followup , no immobilizer or brace was used except in one patient who had undergone acl reconstruction .\nall other patients were encouraged to perform daily active range of motion exercises with quadriceps strengthening and allowed to carry full weight bearing loads immediately .\npreoperative central knee pain on terminal extension was moderate in 10 knees and severe in 8 knees .\npostoperatively , 12 knees showed complete pain relief and 7 showed pain improvement by at least 3 visual analogue scale ( vas ) grades , for a total of 16 had well to excellent results regarding pain on terminal extension .\npreoperative average international knee documentation committee ( ikdc ) score8 was 33.6 which improved postoperatively to the average 73.2 .\nthe flexion deformity was found in four patients , with a mean angle of 6. postoperatively , it improved significantly with no deformity .\nmris of all 20 patients showed an acl that appeared bulky , occupying almost the entire intercondylar notch , with a marked increased signal , particularly in the t2-weighted images , and with a mass - like configuration intertwined with its fibers with celery stalk \nsign.910 on mri , 6 patients had medial compartment arthritis , 4 patients had torn medial meniscus grade iii , and 1 patient had grade ii tear in posterior horn of lateral meniscus .\narthroscopy showed osteoarthritic changes in 9 knees and concomitant degenerative pathologies in 4 knees ; these included meniscal tears and synovitis .\nsix ( 30% ) degenerative lesions of the medial meniscus and 1 ( 0.5% ) degenerative lesion of lateral meniscus were noted .\nthree femoropatellar cartilaginous lesions ( 15% ) , 4 ( 20% ) medial femorotibial lesions ( two grade 1 , one grade 2 , one grade 3 ) , and 1 ( 0.5% ) lateral femorotibial lesion grade 1 were observed .\nit filled the entire intercondylar notch and was unusually taut , toward 90 of flexion in 2 patients with hypertrophied am bundle of acl , and taut in extension in rest of the patients with hypertrophied pl bundle of acl .\nthe posterolateral portion of the acl bulged into the lateral compartment in extension impinging in the notch . by flexion \nwhen each knee was brought into full extension , impingement of the hypertrophied acl to the lateral wall and roof of the intercondylar notch was observed.1112 impingement was particularly apparent in knees with a severely hypertrophied acl or narrowed notch , as well as limited knee joint extension .\narthroscopic treatment consisted of debridement of the afflicted portion of the acl in all cases . in six knees with evident notch narrowing\n, notchplasty was performed first . because yellowish degenerative hypertrophied lesions were entangled around the posterolateral acl fibers , the anteromedial portion was retained in 18 patients . in 2 patients , posterolateral portion of acl was retained because of hypertrophied degenerated am bundle of acl .\nalthough in one patient after debridement , the remaining portion of the acl was not enough to stabilize the knee , so we had to reconstruct the acl with hamstring graft which is comparable with the study by lintz et al.(7%).1 at an average followup time of 24 months ( range 12 - 36 months ) , all except two patients had a full range of painless motion .\nit was 1 grade higher as compared with the opposite knee in 14 knees and the same as the opposite knee in 6 knees .\nall patients had a firm endpoint on lachman test without any symptoms of instability , inferring some intact portion of the acl between the tibia and the femur .\ntwo patients had pivot shift positive + 1 with glide and 18 patients had negative pivot shift .\na soft endpoint on anterior translation would imply no intact acl tissue in the intercondylar area . the histopathologic appearance and reports of the biopsy specimens were consistent with mucoid degeneration of the acl .\nregression of the size and bulkiness of the treated acl was seen , with the t2-weighted images showing decreased signal with some intact acl fibers between the tibia and femur .\nthe mucoid hypertrophy of the acl is a rare condition found in middle - aged individuals .\nmucoid degeneration of anterior cruciate ligament is not an uncommon pathology , but is often unknown . according to bergin\net al.6 and salvati et al.,13 reported its occurrence as 2 and 5% , respectively , of knee where mri was done .\nour findings were incidental in initial 4 cases where clinical and radiological findings were not correlated as radiologist reported partial rupture of acl only . in practice and in the literature , it is often confused with a diagnosis of partial acl rupture . it becomes apparent in two subpopulations of patients .\nthe first group is younger , active , athletic , in whom we can assume an acl mechanism affected by real trauma or repeated microtraumas causing an early lesion.14 the second group is older and presents with progressive degenerative acl lesions , with frequent concomitant degenerative meniscal lesions .\nthe pathogenesis of mucoid degeneration is unclear , but injury , ganglion cysts , and degenerative process leading to loss of synovial lining have been implicated as the most likely etiologic factors in the production of this change . in younger group\nthe possible cause of repetitive minor trauma is impingement of the acl to the lateral wall and roof of the narrow notch , which has been reported to be more common in female patients.15 in second group there is subtle alterations in joint kinematics due to osteoarthritis , meniscal tears , and other degenerative changes , leading to stretching of cruciate ligaments .\nfealy et al.16 suggested that knee pain on flexion might be caused by tensioning of the diseased am bundle of the acl .\nfor kumar et al.18 the pain is attributable to the effect of the acl mass in the posterior notch .\nhsu et al.19 and kim et al.11 attribute it to incarceration of the pathological acl in the posterior femoro - tibial compartment .\nhowever , we found that the hypertrophied acl bulged into the lateral compartment , impinged on the lateral tibiofemoral joint , and caused an extension or flexion block , depending on the position of the impingement in the lateral tibiofemoral joint .\nwe believe the most important source of pain is mechanical impingement , associated with unique function of the acl in providing nociceptive sensory signals .\nit is mentioned elsewhere only by mcintyre et al.2 who reported one case of atraumatic acl rupture at 1 postoperative year after partial resection .\nour results indicate that postoperative laxity , largely asymptomatic , can increase anterior laxity over time and evoke instability .\nmucoid hypertrophy of the acl should be clinically suspected in elderly person presenting with persistent knee pain on terminal extension without preceding trauma , especially when associated with extension deficit , which is more common in elderly individual with degenerated knee .\narthroscopic debridement of mucoid hypertrophy of the acl in conjunction with notchplasty can effectively provide symptomatic improvement without instability .", "answer": "background : mucoid degeneration of the anterior cruciate ligament ( acl ) is a less understood entity . the purpose of this study was to diagnose mucoid degeneration of anterior cruciate ligament and to assess the effectiveness of arthroscopic treatment in these patients.materials and methods : between december 2007 and november 2011 , 20 patients were diagnosed to be suffering from mucoid degeneration of anterior cruciate ligament ( acl ) on the basis of magnetic resonance imaging ( mri ) , histopathology , and arthroscopy findings . \n 12 patients were males and 8 patients were females , with mean age of 42.2 years for males ( range 28 - 52 years ) and 39.4 years for females ( range 3054 years ) . \n they presented with pain on terminal extension ( n=10 ) and on terminal flexion ( n=2 ) without history of significant preceding trauma . \n mri showed an increased signal in the substance of the acl both in the t1- and t2-weighted images , with a mass - like configuration that was reported as a partial or complete tear of the acl by the radiologist . at arthroscopy , \n the acl was homogenous , bulbous , hypertrophied , and taut , occupying the entire intercondylar notch . \n a debulking of the acl was performed by a judicious excision of the degenerated mucoid tissue , taking care to leave behind as much of the intact acl as possible . releasing it and performing a notchplasty treated impingement of the acl to the roof and lateral wall . in one patient , we had to replace acl due to insufficient tissue left behind to support the knee.results:good to excellent pain relief on terminal flexion extension was obtained in 19 of 20 knees . \n the extension deficit was normalized in all knees . \n lachman and anterior drawer test showed a firm endpoint in all , and 85% ( n=17 ) showed good to excellent subjective satisfaction.conclusions:mucoid hypertrophy of the acl should be suspected in elderly persons presenting pain on terminal extension or flexion without preceding trauma , especially when there is no associated meniscal lesion or ligamentous insufficiency . \n they respond well to a judicious arthroscopic release of the acl with notchplasty .", "id": 338} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsuccess in endodontic treatment is best defined by the contemporary endodontic triad of diagnosis , anatomy , and debridement . in the learning curve of endodontics ,\nthe incisor tooth forms the basics due to its simple morphology of one root - one canal .\nthe common developmental anomalies in a maxillary lateral incisor ( mli ) includes peg - shaped crown , radicular groove , talon cusp , and dens invaginatus ( di ) . from an endodontic perspective\nconsidering the occurrence of additional canals , the literature shows that , mli with a maximum of four canals and with dens formation , three root canals have been reported .\nteeth with di are often recognized clinically due to their unusual crown form or extremely marked foramen caecum and many a time may show no clinical signs of the malformation .\nhowever , due to the limitation of conventional radiographs in assessing root canal configuration , complex root canal morphology due to dental anomalies such as multiple root canals , two roots and dens formation poses a considerable diagnostic challenge to achieve the required success .\nnevertheless , advanced radiographic techniques such as the cone beam computed tomogram ( cbct ) helps in a three - dimensional evaluation of a particular tooth to overcome the limitations of conventional radiography .\nthe purpose of the present case report is to discuss the endodontic procedure adopted to negotiate the complex tooth morphology of a peg - shaped mli with di and five root canals ( frc ) .\nthe present case is about a 17-year - old male patient who was referred to the department of endodontics with a primary complaint of heaviness and pain in relation to the upper front tooth .\nclinical evaluation revealed no significant extraoral findings . on intraoral examination , both the mlis appeared peg - shaped .\nhowever , the right lateral incisor was associated with a soft tissue swelling in the labial vestibule [ figure 1a ] , tender on percussion and gave a negative response to electric pulp testing .\nintra oral periapical radiograph of the maxillary right lateral incisor revealed ill - defined periapical radiolucency associated with an unusual canal morphology and di [ figure 1b ] . based on the clinical and radiological findings\n( a ) peg - shaped lateral incisor with intra - oral swelling in the labial vestibule .\n( b ) radiograph revealing periapical radiolucency associated with right lateral incisor and presence of dens invaginatus .\n( d ) radiograph with instruments in five canals the need for an endodontic therapy was explained to the patient and was advised to take a course of analgesics and antibiotics ( amoxicillin 500 mg , metronidazole 400 mg , ibuprofen 400 mg thrice daily for 5 days ) .\nthe patient was administered local anesthesia of 2% lidocaine with 1:100,000 epinephrine . under rubber dam isolation ,\nan access opening was made and an orifice ( c1 ) was visualized after copious amount of purulent discharge was allowed to drain through the c1 .\nthe endodontic explorer was placed in the c1 and verified with an apex locator ( sybron endo mini , sybron endo , glendora , usa ) and radiograph .\nhowever , as the drainage of purulent discharge persisted , a calcium hydroxide intra - canal medicament ( calcicur , voco , cuxhaven , germany ) was placed and access cavity was temporarily sealed .\n( cavit , 3 m espe ag , seefold , germany ) . after 3 days\n, the calcium hydroxide was removed from c1 and subtle changes were noted at some points over the sub - pulpal floor , which suggested the possibility of additional canals away from the c1 that was located on the labial half . in order to locate the possibility of a palatal canal , the access cavity was redefined in the distopalatal ( dp ) region and the second canal ( c2 )\nwas identified and negotiated successfully . on further probing in the distolabial ( dl ) region , two additional orifices ( c3 and c4 )\nhowever , the orifices of c3 and c4 were interconnected . with four instruments placed in the respective canals , the radiograph showed the presence of another unidentified canal .\nthe fifth canal orifice ( c5 ) was located at the mesiopalatal ( mp ) aspect , summing - up to five canals all with separate apical exit [ figure 1c and d ] .\neach time an orifice was identified , it was checked with an apex locator to rule out perforation .\ncoronal flaring alone was performed with protaper rotary ni ti instruments ( dentsply , maillefer ) and subsequent cleaning and shaping was completed by hand instrumentation ( dentsply , maillefer ) due to the constricted coronal pulp space .\na cbct scanning was done to study the tooth morphology , which confirmed the presence of a single root with five canals with separate apical exit and a type iii di [ figure 2a and b ] .\n( c ) radiograph taken after root canal filling and placement of temporary restoration in the access cavity .\n( d ) follow - up radiograph after 12 months showing signs of healing one week later the tooth was obturated in the third visit , with gutta - percha and sealer ( apexit , ivoclar vivadent ) by cold lateral compaction technique [ figure 2c ] .\nthe patient was periodically monitored , with satisfactory healing and the follow - up period of 12 months was uneventful [ figure 2d ] .\ndens invaginatus is a developmental malformation resulting from invagination of the crown or root before calcification has occurred . with a reported incidence from 0.04% to 10%\n, di can be found affecting either the primary or the permanent dentition , and commonly involving the mlis .\ncases of bilateral occurrence and rare cases are reported in molars , premolars , and maxillary central incisors .\nan indian study reported a prevalence of 0.5% of surveyed teeth ; however , according to a chinese study , di was found in 517 permanent teeth from 67 chinese individuals , which account for 5% of di .\nthe literature shows that mli with a maximum of four canals has been reported , but as far as the author 's knowledge , this is the first case with frc , especially in a peg - shaped lateral incisor complicated by the presence of di . according to the literature , di in a mli is considered as unusual .\ntype 2 involves the root , but does not reach the apex , and in type 3 , the invagination extends past the periapical region with and without manifesting an additional apical foramen .\nthe pathways of infection in a di is found to be due to hypomineralized internal enamel and the thin canals or fissures in the dentin connecting the invagination to the pulp cavity through which microorganisms and irritating agents from the oral cavity gain access to the pulpal space leading to pulp alterations .\nthe challenge posed in this case is the restricted access coupled with complex and unpredictable morphology of the root canal system .\nkrape and fidler emphasized the need and suggested incisal edge as the predominant location of straight - line access in anterior teeth .\nvarious treatment techniques have been reported in the literature , including preventive sealing or filling of the invagination , root canal treatment with or without endodontic apical surgery , intentional replantation and extraction .\nremoval of di using hand files and gates glidden drills and with the aid of an operating microscope and subsequent root canal treatment has also been described .\nthe presence of multiple root canals in a peg - shaped mli complicated by di poses substantial difficulty in diagnosis and treatment as well as achieving endodontic success for better prognosis .\nthe present case has been evaluated and negotiated with the aid of conventional radiographs and by applying law of symmetry , cemento enamel junction and orifice location .\nthe complicated tooth morphology with multiple root canals warrant use of cbct to define and confirm the canal morphology .\nin line with a molar tooth , the multiple canals in this case is named according to the surface in which it is located namely c1 mesiolabial , c2 dp , c3 and c4 dl1 and dl2 , and c5 mp , respectively [ figure 1c ] .\ncase selection is the key in successful outcome of a treatment . treating a tooth with a unique morphology\ndefinitely tests the clinical knowledge , skill of the operator and one should be ready for any kind of pulp space variant that could exist . although , cbct would have been beneficial to precisely define and confirm the canal location in a complicated morphology , the present case illustrates the successful negotiation with conventional radiographs .", "answer": "this case report describes endodontic treatment completed in a peg - shaped maxillary lateral incisor , with single root and five root canals of which , one is due to dens invaginatus . \n cone beam computed tomogram scanning confirmed the unique morphology of the tooth . \n new nomenclature for the five canals is proposed .", "id": 339} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na safe and efficient hemostasis is one of the most important factors in minimally invasive surgery .\nhemostasis can be achieved by sutures , clips , application of hemostyptica or thermic coagulation . for thermic coagulation , high - frequency ( hf ) coagulation in monopolar or bipolar mode , cold plasma , and ultrasonic coagulation\nklingele compared the ultrasonic technique with the bipolar technique in dissected vessels and examined the tissue damage .\nunderwood et al . measured the differences in operative time , blood loss and complications when using bipolar or ultrasonic technique in colectomies and fundoplications [ 7 , 8 ] .\nsutton et al . examined the lateral thermal spread using monopolar and bipolar diathermy , the harmonic scalpel and ligasure by measuring the maximum temperature . in our present study\nthe tests were performed on perfused , isolated pig liver in a minimally invasive model with a pulsatile organ perfusion ( p.o.p . ) trainer . for analysis\na complete laparoscopic equipment setup for minimally invasive surgery was used together with a p.o.p .\nthe experimental procedure began with heating the isolated , frozen liver in a water - cooled vacuum in order to warm it up to about 30c35c before the actual start of the experiment .\nthe pump of the trainer was activated to check the correct function ( figure 2 ) .\nsmall open vessels on the liver surface were closed with sutures . after a final check of the correct connection of blood vessels ,\nafter 30 minutes , the tissue temperature was detected by the laboratory thermometer at 5-minute intervals until it reached 37c . to start the experiment ,\na 2 - 3 cm thick slice of the liver was resected to create a deep tissue bleeding .\nafter closure of the cover , the pump was activated again ; the bleeding area was photodocumented ( figure 3 ) . \nthe cut surface was divided horizontally in two halves . only the upper half was coagulated to see the difference to untreated tissue and calculate the tissue loss ( figure 4 ) .\nthe coagulation was started using one of the four techniques until the bleeding could be stopped . using ultrasonic coagulation\n, it was not possible to create hemostasis in preliminary experiments for hemostasis of large bleeding areas in perfused pig liver .\nafter 5 minutes , the cell walls were highlighted and a first approach of coagulated tissue became visible .\nthe bleeding did not stop ; the extraction of tissue by the mechanical vibrations of the ultrasonic applicator could be observed .\nafter 10 minutes , there was an increase of foam ; after 15 minutes , we saw extracted tissue without sufficient hemostasis ( figures 5 and 6 ) . \nbased on these preliminary tests , the ultrasonic technique was not considered for further experiments and pathological examination . using the other devices , after stopping the pump and opening the cover ,\nthe tissue was fixed on a cork plate and placed in formalin solution after photodocumentation . from the resected tissue ,\n10 cuts in 510 mm distance were made , each cut was examined at 10 points microscopically ( figure 7 ) .\nfurthermore , the maximum tissue damage was determined to compare the tissue loss caused by the different techniques .\nthe high - frequency coagulation devices were used with the settings shown in table 1 .\nthe gas flow had little effect ( cooling ) on the coagulation performance . with 1.5 l / min gas flow ,\nforced coag was chosen because the required output voltage of the monopolar technique for a similar coagulation is significantly higher than in bipolar technology .\nthe tissue structure changes on the necrotic side the color is darker in the thermally damaged area . \nmicroscopically the necrotic cells are not clearly defined and shrank because of the evaporated water . in addition , the color is very dark compared with the nondamaged tissue . \nthe 10 measuring points are lined up linearly , so that the measurements cover a distance of 1 mm of the tissue sample .\nthe tissue loss is measured in relation to the lower half of the untreated sample at the point of greatest loss .\nthe measurement can be easily carried out macroscopically ( figure 4 ) . for statistical evaluation of tissue damage and tissue loss ,\nwe measured the coagulation time of 3 different techniques ( monopolar , bipolar , and cold plasma ) on 4 experimental days .\nultrasonic coagulation was excluded , because hemostasis of large bleeding areas could not be reached . as shown in figure 9 , the shortest time\nthere was almost no difference between monopolar ( 11 min ) and cold plasma ( 11.25 min ) . to determine the tissue loss ,\nthe height difference between the coagulated area and the untreated area was macroscopically analyzed and measured in mm ( figure 10 ) .\nthe minimal tissue loss was 4 mm ( bipolar coagulation ) ; the maximal tissue loss of 8 mm occurred using cold plasma coagulation . on average ,\nthe tissue loss was the least in bipolar technique ( 4.5 mm ) , more in monopolar technique ( 6.0 mm ) , and most in cold plasma coagulation ( 7.5 mm ) .\nthe depth of tissue necrosis was analyzed microscopically and measured in mm ( figure 11 ) .\nthe lowest value was found in cold plasma coagulation ( 0.157 mm ) , the highest in monopolar coagulation ( 0.598 mm ) .\nthe slightest average damage to the tissue was observed in cold plasma coagulation with a mean of 0.264 mm .\nbipolar coagulation led to an average depth of 0.346 mm , monopolar coagulation of 0.459 mm .\nbipolar coagulation of large bleeding areas of the perfused pig liver led to a rapid hemostasis causing moderate tissue damage and depth loss .\nthe worst results occurred with monopolar coagulation compared to bipolar technique ( coagulation time + 33.3% , tissue loss + 33.3% , tissue damage + 32.7% ) .\nultrasonic coagulation was excluded because large bleeding areas could not be treated sufficiently and hemostasis was not reached .\nthe aim of this study was to examine whether there are differences between the common coagulation techniques in a minimally invasive model concerning the efficiency of hemostasis and local tissue damage [ 1 , 3 ] . the experiments were done with isolated , perfused pig livers .\nthe use of ultrasonic coagulation did not lead to a complete hemostasis even after 15-minute coagulation time .\nthe termination resulted from the application form of energy causing foam formation and extraction of tissue components .\nthe benefits of ultrasonic technology in minimally invasive surgery are clear in the preparation and dissection of tissue , the use close to other organs , and the closure of isolated vessels of up to 57 mm . in our model , it was not useful for coagulation of large bleeding areas .\nthe first parameter in this study was the coagulation time until a sufficient hemostasis was reached .\na good instrument should be safe and quick to reduce damage to lateral tissue and to minimize the energy flow to the patient .\nwe know from clinical use that with longer monopolar coagulation time more and more necrotic tissue sticks to the instrument and is pulled out .\nthe average tissue loss was 4.5 mm in bipolar technique and 6.0 mm in monopolar technique ( cold plasma coagulation 7.5 mm ) .\nthe depth of tissue damage by coagulation was the third parameter in this study . because of the high efficiency of bipolar coagulation , less energy was needed to stop the bleeding .\nthis resulted in an average depth of tissue necrosis of 0.346 mm in bipolar coagulation and 0.459 mm in monopolar coagulation .\nit showed the longest coagulation time and the highest tissue loss , while the depth of tissue damage was the lowest in this study .\none possible explanation could be the gas , which is pressed into the tissue during the contactless coagulation .\nit leads to a deep dissection of necrotic tissue and a rapid shrinkage of the particles ( figure 13 ) .\nthis indicates a low degree of necrosis and corresponds with the previously mentioned results ( figure 14 ) .\nafter monopolar coagulation , we regularly see black carbonized tissue ( figure 15 ) , after cold plasma coagulation grey - brown to black tissue ( figure 16 ) . in summary ,\nthe collateral tissue damage consisted of the tissue loss and the tissue necrosis in the depth . when both factors are added , the total damage can be calculated ( table 2 ) .\nthe results of this work came from experiments on isolated pig livers in an in vitro test environment and can not be easily transferred to human application .\nperfusion of the isolated liver was achieved with colored saline solution and not with blood , what restricts hemostasis and prolongs the coagulation time .\nthis is one reason for the relatively long coagulation time that we measured in the perfused liver .\nfurther studies have to show the presumed superiority of bipolar technique . in our surgical department\nthe experimental study showed differences between several coagulation techniques in a minimally invasive model for hemostasis in deep liver bleeding .\nultrasonic coagulation , which is very useful in dissection of tissue and coagulation of isolated vessels , did not lead to a sufficient hemostasis in large bleeding areas .\nthe bipolar technique was the form of coagulation with the highest efficiency and the least tissue damage .", "answer": "hemostasis in minimally invasive surgery causes tissue damage . regardless of the method of production of thermal energy , \n a quick and safe coagulation is essential for its clinical use . in this study \n we examined the tissue damage in the isolated perfused pig liver using monopolar , bipolar , cold plasma , and ultrasonic coagulation . in a \n minimally invasive in vitro setup , a 2 - 3 cm slice of the edge of the perfused pig liver was resected . \n after hemostasis was achieved , liver tissue of the coagulated area was given to histopathological examination . \n the depth of tissue necrosis , the height of tissue loss , and the time until sufficient hemostasis was reached were analyzed . \n the lowest risk for extensive tissue damage could be shown for the bipolar technique , combined with the highest efficiency in hemostasis . \n using cold plasma , coagulation time was longer with a deeper tissue damage . \n monopolar technique showed the worst results with the highest tissue damage and a long coagulation time . \n ultrasonic coagulation was not useful for coagulation of large bleeding areas . \n in summary , bipolar technique led to less tissue damage and best coagulation results in our minimally invasive model . \n these results could be important to recommend bipolar coagulation for clinical use in minimally invasive surgery .", "id": 340} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhyperpigmentation of the gingiva has always been a concern to certain patients , especially young females .\nalthough melanin pigmentation of the gingiva is completely benign and does not present a medical problem , its unaesthetic appearance as black gums is more pronounced in patients having a high smile line ( gummy smile ) .\n gummy smile can be due to incomplete passive eruption , maxillary protrusion , hyperactive muscle of lips , short lip , gingival enlargement , etc .\ngingival depigmentation can also be performed by surgical blade , coarse diamond bur , electrosurgery , cryosurgery or lasers . considering the advantages of lasers over other modalities of treatment , this article will focus on the management of such a case using gaalas diode lasers of 810 nm .\na 22-year - old female patient was referred with a complaint of gummy smile and hyperpigmented gingiva [ figure 1 ] . on examination , pseudopockets ( approximately 23 mm ) were detected in the maxillary and mandibular anteriors along with generalized excessive amount of melanin pigmentation on the gingiva [ figure 2 ] .\nthe patient was explained about the treatment options and informed that , after depigmentation , melanin pigmentation tends to recur and , as gingivectomy is also performed simultaneously , the overall appearance would be worth doing it .\nprofile view of gummy smile with hyper melanin pigmentation of the gingiva intraoral view of gummy smile with hyper melanin pigmentation of the gingiva gingivectomy and depigmentation were planned in the 1525 region and the 3444 region using a 810 nm diode laser .\nalthough procedures like this can be performed under topical anesthesia , infiltration was planned as the patient was anxious and sensitive . under infiltration anesthesia with 2% lignocaine ( with 1:100,000 adrenaline ) , an 810 nm gaalas diode laser ( picasso)*(picasso , by amd lasers ) was used in contact mode with the gingival tissues .\ne gel was prescribed for local application -three to four times a day for 2 days . because a large area of the raw wound was kept exposed , antibiotic cap .\nimmediate postoperative view of gingivectomy and depigmentation using an 810 nm diode laser the patient reported no adverse effects or discomfort during the postoperative healing phase .\nshe was happy and satisfied with 6-month postoperative results [ figures 4 and 5 ] .\ngingivectomy and depigmentation were planned in the 1525 region and the 3444 region using a 810 nm diode laser .\nalthough procedures like this can be performed under topical anesthesia , infiltration was planned as the patient was anxious and sensitive .\nunder infiltration anesthesia with 2% lignocaine ( with 1:100,000 adrenaline ) , an 810 nm gaalas diode laser ( picasso)*(picasso , by amd lasers ) was used in contact mode with the gingival tissues .\ne gel was prescribed for local application -three to four times a day for 2 days . because a large area of the raw wound was kept exposed , antibiotic cap .\nimmediate postoperative view of gingivectomy and depigmentation using an 810 nm diode laser the patient reported no adverse effects or discomfort during the postoperative healing phase .\nshe was happy and satisfied with 6-month postoperative results [ figures 4 and 5 ] .\ndiode laser is a versatile laser and has been successfully used at three wavelengths : 980 nm , 810 nm and , more recently , 940 nm .\nit has numerous soft tissue applications , viz frenectomy , crown lengthening , gingival depigmentation , troughing , etc . in a diode laser ,\nthe substance stimulated to produce a coherent light beam is a semiconductor . this technology has produced a laser that is compact and economic .\na diode laser has become an important tool in the dental armamentarium due to its exceptional ease of use and affordability .\nthe diode laser is well absorbed by melanin , hemoglobin and other chromophores that are present in periodontal disease .\nthis provides the diode laser with broad clinical utility : it cuts precisely , coagulates , ablates and vaporizes the target tissue with much less trauma , improved postoperative healing and faster recovery time .\nmelanin pigmentation in gingiva is present only when melanin granules synthesized by melanocytes are transferred to the keratinocytes .\ntherefore , recurrence of the pigmentation is inevitable and has been reported from 24 h to 8 years following surgery .\nconventional procedures for corrections of pigmented gingiva consist of surgical stripping with scalpel , use of electrosurgery , cryosurgery or a coarse diamond bur . however , the laser is the least - invasive and predictable method of performing this procedure .\nit has a high level of precision , requires minimal anesthesia and causes very low collateral tissue damage .\ncases where only gingivectomy is required can be performed without anesthesia or under topical anesthesia , but because both gingivectomy and depigmentation were planned together in this patient and a significantly larger area needs to be operated upon , infiltration anesthesia was given .\ngiven the incredible ease of use and its versatility in treating soft tissue , the diode laser becomes the \npatients with complaints of hyperpigmented gingiva should also be assessed for the presence of gummy smile .\nonce the amount of gingiva displayed is reduced by gingivectomy , the patient 's concern for hyperpigmented gingiva will also reduce . as a result , in most of the cases , a repeat surgery for depigmentation", "answer": "hyperpigmentation of gingiva becomes more pronounced if it is associated with \n gummy smile . \n correction of gummy smile and depigmentation together are key to complete patient satisfaction . \n an 810 nm ( 1.5 w , pulsed ) gaalas diode laser was used to achieve the desired results in a 22-year - old female patient . \n the 6-month follow - up results showed excellent color and contour of the gingiva . \n mere depigmentation without correcting gummy smile may look cosmetically good but esthetically unacceptable . \n diode laser was used as it is known to be an excellent tool as compared with other conventional surgical procedures in terms of patient and operator comfort .", "id": 341} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nGeometric and energetic data from quantum chemical calculations of halobenzenes and xylenes Authors\n\nPaper sections:\nValue of the Data\n\u2022 All 1505 possible halobenzenes and three xylenes are explicitly shown in this paper with numbering, IUPAC name, PubChem CID and SMILES. These can be used as a reference for both theoretical and experimental work involving this class of compounds. \u2022 Geometric and energetic data can be used for further analysis to understand relative stability of isomers.
In particular, the unexpected trend in relative stability of isomers are of particular interest to scientists in a similar manner to cis and gauche effect. The data set includes many examples where steric hindrance alone fails to account for the behaviour observed in halobenzenes and xylenes. \u2022 Raw data as well as associated scripts and codes are provided so that interested researchers can reproduce our data and perform calculation at other levels of theory or for other relevant class of compounds.
Vibrational spectrum and other detailed information can be extracted from output files as needed. There are many potential uses of the spectral information, for example, detection of xylene for food safety application [1] and understanding formation of polychlorinated biphenyls (PCBs). [2] The data can also be a test set for molecular modelling software packages.
\n\nData Description\nA total of 1505 unique compounds of benzene, including all degrees of substitution with F, Cl, Br, and I atoms, and three isomers of xylene were investigated. Classification and counting of the 1505 compounds are exhaustively shown in Tables 1 and 2 with specific examples in Figures 1, 2 and 3. The main difference between Table 1 and Table 2 is the treatment of hydrogen atom. In Table 1, hydrogen is treated in the same way as halogen and this leads to the binomial coefficients ( 5 \ud835\udc58 ) for five kinds of elements. In Table 2, hydrogen is treated in a special way and this leads to binomial coefficients ( 4 \ud835\udc58 ) for four kinds of halogen atoms. Table 3 summarizes the total number of Q-Chem 5.2.1 [3] output files for different classes of compounds, types of calculation (geometry optimization/frequency calculation) and levels of theory (HF, B3LYP, MP2, and CCSD)
In supplementary information, summary table files (.csv) are provided per level of theory.
\u2022 Geometric data of 12 bond lengths, 12 bond angles and 12 torsional angles in a single csv file \u2022 Energetic data, in separate files, include electronic energy (Eelec) in Hartree, thermal correction to enthalpy (Hcorr) in kcal mol -1 , zero-point vibrational energy (EZPE) in kcal mol -1 and entropy (S) in cal mol -1 K -1 . The following associated files are also provided.
\u2022 Raw Q-Chem output files (.out) for all compounds.
\u2022 Geometry in Z-matrix and Cartesian coordinate format (.xyz) for all compounds.
\u2022 Wolfram Mathematica notebook (benzene.nb) and associated script (script.txt).
\n\nExperimental Design, Materials, and Methods\nDue to prohibitive computational cost, frequency calculations at MP2 and CCSD levels of theory were excluded and only benzene to dihalobenzenes and xylenes were selected for CCSD optimization jobs. The output files were processed by custom-made scripts and Wolfram Mathematica 12.0[4] codes to extract geometric and energetic data of all halobenzene compounds in a similar manner to our previous work. [5] Data from the three xylene compounds are provided for reference purpose and were read from IQmol 2.13 manually. [6] Table 1 List of all compounds by the number of elements bonded to carbon atoms (In total, there are 1,505 benzene and halobenzene compounds with 210 possible empirical formulas.) a See Figure 1. b See Figure 2.
\n\nNumber of structures\n) =60 Table 2 List of all compounds by different degrees of substitution to benzene (In total, the number of compounds and empirical formulas is the same as in Table 1.)
Benzene 0 C6H6
", "answer": "This article presents theoretical data on geometric and energetic features of halobenzenes and xylenes. Data were obtained from ab initio geometry optimization and frequency calculations at HF, B3LYP, MP2 and CCSD levels of theory on 6-311++G(d,p) basis set. In total, 1504 structures of halobenzenes, three structures of xylenes and one structure of benzene were generated and processed by custom-made codes in Mathematica. The quantum chemical calculation was completed in Q-Chem software package. Geometric and energetic data of the compounds are presented in this paper as supplementary tables. Raw output files as well as codes and scripts associated with production and extraction of data are also provided.", "id": 342} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe measured the differences in stiffness between extrafloral nectaries of v. faba and the tissue that surrounds them .\nwe mounted 20 stipules from 20 , 18-day - old plants on adhesive tape that was attached ( sticky side up ) to the surface of a piece of flat styrofoam .\nwe did a penetrometer test to measure the initial modulus of rigidity of the spot being tested , using a texture analyzer ( ta.xt2i , stable micro systems , surrey , uk ) fitted with a 10 stainless steel cone moving at 0.5 mm / s . in each stipule\n, one measurement was done in the center of the extrafloral nectary and 3 measurements were done in random locations on the stipule . for each stipule , an average \nstipule stiffness was calculated from these 3 measurements and this value was compared with the measured stiffness of the extrafloral nectary on that stipule .", "answer": "abstractextrafloral nectaries play an important role in plant defense against herbivores by providing nectar rewards that attract ants and other carnivorous insects \n . however , extrafloral nectaries can themselves be targets of herbivory , in addition to being exploited by nectar - robbing insects that do not provide defensive services . \n we recently found that the extrafloral nectaries of vicia faba plants , as well as immediately adjacent tissues , exhibit high concentrations of chemical toxins , apparently as a defense against herbivory . here \n we report that the nectary tissues of this plant also exhibit high levels of structural stiffness compared to surrounding tissues , likely due to cell wall lignification and the concentration of calcium oxalate crystals in nectary tissues , which may provide an additional deterrent to herbivore feeding on nectary tissues .", "id": 343} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndual energy photon absorptiometry ( dxa ) has long been the standard for monitoring areal bmd ( abmd ) .\nwe have compared vbmd measured by high resolution peripheral computerized tomography ( hr - pqct ) with the results obtained by dxa ( abmd ) in a group of 49 of healthy premenopausal , normally menstruating women , aged 21 - 45 , spanning a range of bmi ( 18.5 - 46.5 ) .\nthey were exercising less than 4 hours per week , and did not have conditions or medications known to affect bone ; we wanted to see if the results of scanning with hr - pqct paralleled those of dxa in subjects with a wide range of bmi .\nthe subjects gave informed consent and the study was approved by our institutional review board .\nusing data from 187 females between 18 and 45 yrs , the mean and standard deviation for the total body bone density by dxa are 1.2044 and 0.1107 . using these results and assuming a correlation between the two measurements of bmd equal to 0.7 , gives a standard deviation for the difference between two measurements equal to 0.0857 .\na sample of size 45 has a power of 80% for detecting a difference between mean bmd of the two instruments equal to 0.0386 .\nthis corresponds to detecting a difference equal to 3.2% of the mean areal bmd of all bones in all areas was measured by dxa ( ge lunar idxa , hawaii , usa ) in whole body mode .\nparticipants were measured on the same densitometer with the same software , scan speed and technologist .\nthe long term precision was 0.35% , and the least significant change for bmd measurements was 1.00% .\nthe software provides values for the masses of muscle , fat , and bone for the whole body and specific regions .\nstructural bone parameters of the non - dominant distal radius and left distal tibia were assessed by hr - pqct ( xtremect scanco medical ag , brutisellen , switzerland . ) a stack of 110 slices with a nominal voxel size of 82 m was obtained with the most distal computerized tomographic ( ct ) slice placed 9.5 mm from the endplate of the radius or 22.5 mm from the endplate of the tibia .\nthe coefficient of variation ( cv ) of a phantom containing hydroxyl - apatite ( ha ) rods embedded in resin ( qem .\nthe voi was automatically separated into a cortical area ( ct ar ) and trabecular area ( tb ar ) .\nd100 is the average vbmd in a scanned region one scan of the distal radius was excluded because the subject was unable to control the shaking of her hand .\nareal bmd of all bones in all areas was measured by dxa ( ge lunar idxa , hawaii , usa ) in whole body mode .\nparticipants were measured on the same densitometer with the same software , scan speed and technologist .\nthe long term precision was 0.35% , and the least significant change for bmd measurements was 1.00% .\nthe software provides values for the masses of muscle , fat , and bone for the whole body and specific regions .\nstructural bone parameters of the non - dominant distal radius and left distal tibia were assessed by hr - pqct ( xtremect scanco medical ag , brutisellen , switzerland . ) a stack of 110 slices with a nominal voxel size of 82 m was obtained with the most distal computerized tomographic ( ct ) slice placed 9.5 mm from the endplate of the radius or 22.5 mm from the endplate of the tibia .\nthe coefficient of variation ( cv ) of a phantom containing hydroxyl - apatite ( ha ) rods embedded in resin ( qem .\nthe voi was automatically separated into a cortical area ( ct ar ) and trabecular area ( tb ar ) .\nd100 is the average vbmd in a scanned region one scan of the distal radius was excluded because the subject was unable to control the shaking of her hand .\ntable 1 shows that the average and compact bone density ( hr - pqct ) are both higher in the radius than in the tibia whereas dxa shows a higher bone density for the legs ( weight bearing bone ) compared to the arms .\nslice area ( which reflects cross sectional area ) and cortical thickness are greater in the tibia than in the radius , and this difference in geometry makes it difficult to interpret the difference in volumetric bone density ( hr - pqct ) ; bone strength is dependent inter alia on cross sectional area and cortical thickness .\nfigure 1 shows that bmd arms is significantly correlated with % fat whereas d100 ( average vbmd by hr - pqct ) , is non - significantly correlated with % fat .\ntable 2 shows that there is significant r between bmd ( dxa ) of legs and arms with bmi as well as w and % fat , whereas there is no significant r between d100 ( hr - pqct ) and these variables .\nthere is no significant r between age and bmd or between age and d100 radius but there is a significant r between age and d100 tibia table 3 shows that sl area ( cross sectional area ) tibia is correlated with w , bmi , % fat , age .\nadult bones expand in diameter throughout adult life , apparently in adaptation to changing mechanical demands seen by hr - pqct , but not by dxa .\nthe increased bone cross sectional area should decrease bmd ( dxa ) with increased bmi , instead of the increase which we found .\nfigure 2 shows the r between d100 radius v % fat and bmd arms v % fat .\nthe residuals of d100 ( hr - pqct ) / bmd ( dxa ) plotted against % fat have no significant r with the radius / arms ( r = 0.186 ns ) but for the tibia / legs , r=0.378 p<0.01 are shown in figure 3 .\nbolotin et al showed that all soft tissue ( fat and muscle ) inhomogeneities could cause inaccuracies as large as 20 - 50% in bmd measured by dxa .\nthey reported that the ratio of fat to lean , and the ratio of yellow to red bone marrow in the region of interest ( roi ) has a major effect on the measured bmd .\nwe have shown in vitro that surrounding fat markedly alters the result of bmd measured by dxa .\nbosy - westphal has shown that the configuration of fat and muscle around the bone and fat within the bone can markedly alter the measured bmd result .\nthis is probably because dxa can distinguish only two components in one pixel using the attenuation ratio of two different x - ray energies , whereas the output actually consists of three components , bone , fat , and muscle . in pixels containing bone , the composition of the soft tissue\ncan not be measured , and so in those pixels , soft tissue has to be extrapolated from adjacent areas .\nthis assumption is invalid if the composition of the soft tissue in front of or behind the bone or the bone marrow fat differs in composition from soft tissue next to the bone .\nan undetected loss of fat either in front of , behind , or within the bone leads to an increase in pixel density that may lead to an overestimation of bmd .. the difference in r between bmi and the bone parameters measured by hr - pqct and those measured by dxa may possibly be explained by a difference in the effect of fat on the absorption of x - rays causing an artifactual increase in bmd measured by dxa .\nthe measurement of bmd by hr - pqct did not parallel those of dxa in subjects with increasing bmi .\nour results by hr - pqct were obtained with scanco i which has a voxel size of 82 m .\nthe results of scanco i partially depend on identification of bone obtained by the absorption of x - rays in the voi .\nthis study should be repeated with scanco ii.which is a second generation hr - pqct scanner with a voxel size of 61 m .\nthis will provide a geometric measurement of the amount of bone , the result of which does not depend on the absorption of x - rays .\nwe have shown by radiogrammetry that geometric measurements of bone thickness are not altered by surrounding fat .\nthe decreased dependence ( with scanco ii ) on absorption of x - rays , may permit a more accurate assessment of the ability of hr - pqct to measure bmd independently of the amount of surrounding fat .\nhr - pqct shows that increasing bmi is associated with increased bone cross - section .\nthis would tend to decrease measured bmd ( dxa ) as opposed to the increase which we observed with increasing bmi .\nour study suggests that the increased bmd ( dxa ) found with increased bmi may partly be an artifact caused by absorption of x - rays by fat and muscle .\nit is important to validate the measurement of bmd by dxa in the context of obesity because of the large number of studies which depend on it .", "answer": "objectivewas to compare the measurement of areal bone mineral density ( abmd ) by dual energy x - ray absorptiometry ( dxa ) with the measurement of volumetric bone mineral density ( vbmd ) by high resolution peripheral computerised tomography(hr - pqct ) in subjects with a wide range of body mass indices ( bmi).subjectswe scanned the arms and legs of 49 premenopausal women , aged 21 - 45 , with bmi from 18.5 - 46.5 , by high resolution peripheral computerized tomography ( hr - pqct ) and found that there was a non - significant change in volumetric bmd ( vbmd ) associated with increased bmi whereas abmd ( dxa ) was associated with a positive significant increase.hr-pqct scans a slice at the extremity of the tibia and radius , whereas dxa scans the entire leg and arm.resultsthe correlation coefficients ( r ) of bmd ( dxa ) of the legs with bmi were 0.552 p<0.001 , % fat 0.378 , p<0.01 , and w 0.633 , p<0.001 . \n the r of bmd ( dxa ) of the arms with bmi 0.804 p<0.001 , with % fat 0.599 p<0.001 , and with w 0.831 p<0.001 whereas the r of the average bone density ( d 100 ) of legs and arms measured by hr - pqct with bmi , w , and % fat , were not significant.conclusionsalthough hr - pqct and dxa scan different parts of the bone , the high r of bmd with bmi and low r of bone density measured by hr - pqct with bmi suggests that bmd measured by dxa is artifactually increased in the presence of obesity .", "id": 344} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncervical spondylosis is a common cause of chronic neck pain , radiculopathy and/or myelopathy resulting in significant disability .\nwhen patients do not respond to conservative therapy , anterior cervical discectomy and fusion ( acdf ) usually is used to achieve neural decompression , maintain cervical lordosis , and provide segmental stabilization . in our practice , it was often found that patients with cervical spondylosis tended to have concomitant cervical vertigo symptoms such as tinnitus , headache , blur vision , and palpitation .\nrecent studies have indicated that cervical spondylosis patients with cervical vertigo symptoms could be managed successfully with acdf . in this study , we report 2 cases of cervical spondylosis with concomitant cervical vertigo and hypertension that were treated successfully with acdf .\nthis study obtained the approval of the medical ethics committee of our hospital ( general hospital of armed police force , beijing , china ) .\ncase 1 , a 49-year - old female , was admitted with 2 years of history of chronic neck pain , headache , and episodic vertigo and tinnitus .\nepisode occurred 1 to 2 times every day , and lasted 1 to 2 h each time .\nshe felt numbness of both upper extremities and weakness of all 4 extremities for 1 year .\nphysical examination showed that limited neck motion , slightly diminished sensation in both arms , and brisk deep tendon reflexes .\nradiographic examination of the cervical spine showed mild diminution in the height of the c5/6 disc space ( figure 1 ) .\nmagnetic resonance imaging ( mri ) scan showed cord compression by a large central herniation of c5/6 disc with signs of myelomalacia ( figure 2 ) .\nlateral radiograph of cervical spine before operation showed slight narrowing of the c5/6 disc space . t2-weighted sagittal magnetic resonance imaging ( mri ) revealed a large herniation of c5/6 disc before operation , with marked compression of cervical cord , resulting in myelomalacia .\nthe patient had a 2-year history of hypertension , blood pressure was 160/100 mmhg at onset , and then controlled in the normal range ( 110130/7080 mmhg ) by oral medications ( betaloc , 100 mg , once daily ; enalapril , 10 mg , once daily ) .\ncase 2 , a 60-year - old male , was admitted with 10 years of history of chronic neck pain and stiffness .\nhe also experienced vertigo , palpitation , nausea and vomiting with noted numbness of upper limbs , and heaviness of 4 limbs for over 6 months before admission .\nradiographic examination of the cervical spine revealed large anterior and posterior spur formation at the c5/6 and c6/7 disc levels , severe diminution in the height of the c5/6 disc space , and moderate diminution in the height of the c6/7 disc space .\nmri scan showed cervical canal stenosis with marked cord compression secondary to spondylotic changes in c5/6 and c6/7 discs .\nthe patient had a 1-year history of hypertension ( maximum at 180/120 mmhg ) , which was controlled within the normal range by oral medications ( irbesartan , 150 mg , once daily ; nifedipine sustained release tablets , 20 mg , once daily ; amlodiping besylate , 5 mg , once daily ) .\ncervical spondylotic myelopathy was diagnosed and subsequently cervical anterior surgery was recommended for the 2 patients preoperatively based on clinical findings consistent with imaging study .\ncase 1 underwent acdf at the c5/6 disc level ( figures 3 and 4 ) .\nafter surgery , strength in all 4 limbs was significantly recovered , and symptoms of neck pain , headache , vertigo , and tinnitus disappeared .\ninterestingly , her blood pressure also dropped to within the normal range after surgery even without oral medications .\nlateral radiograph of cervical spine 3 months after operation showed anterior cervical plate fixation with cage fusion at c5/6 disc level .\nt2-weighted sagittal magnetic resonance imaging ( mri ) 7 days after operation showed disappearance of cord compression at c5/6 disc level .\nhis symptoms of cervical vertigo completely disappeared , numbness of both upper limbs significantly released , and muscle strength of 4 limbs obviously increased . similarly to case 1 ,\nher cervical vertigo never recurred , and her blood pressure remained normal without the use of antihypertensive medications .\ncase 2 has undergone a follow - up of 14 months , the patient never had cervical vertigo anymore , and his blood pressure remained normal throughout ( 120130/7585 mmhg ) .\nclinical results indicated that acdf can eliminate the concomitant vertigo symptoms in the 2 patients .\nhowever , the exact mechanisms of resolution of symptoms can not be elucidated precisely . because cervical spondylosis is a common disease , vertigo occurred in patients with cervical spondylosis is of particular importance .\none previous study showed that vertigo was present in 50% of patients with cervical spondylosis , whereas another study identified cervical spondylosis as the cause of dizziness in 65% of elderly patients .\nit has been shown that the patients with cervical spondylosis complaining of vertigo have significant lower blood flow parameters than non - vertigo patients with cervical spondylosis .\ninsufficient blood supply to posterior circulation is called vertebrobasilar insufficiency . the most common complaint in patients with vertebrobasilar insufficiency\ninsufficient blood supply does not necessarily cause symptoms if there is sufficient collateral circulation , whereas a full range of symptoms commonly occur as a result of an insufficient terminal vessel .\nthe vascular supply to the vestibulocochlear organ , being an end artery , makes this organ more susceptible to vertebrobasilar insufficiency .\nneurons , axons , and hair cells in the vestibulocochlear system are known to respond to ischemia by depolarizing , causing transient hyperexcitability with ectopic discharges , manifesting as tinnitus , vertigo , and dizziness .\nit was hypothesized that vertebral artery insufficiency secondary to cervical spondylosis could result in vertigo .\nhowever , the mechanisms of vertigo caused by cervical spondylosis are not clear so far .\nthe mechanical compression on vertebral artery from spurs of the luschka joint was considered as a main mechanism .\nthe reduction of vertebral artery flow can be more obvious with the rotation and hyperextension of the head . in our current study\nin addition , mechanical compression can not explain some other symptoms such as palpitation , nausea , vomiting , etc .\nrecent clinical studies by hong et al and li et al demonstrated that the stimulation of the sympathetic nerve fibers other than the compression of the vertebral artery induces these symptoms such as vertigo , tinnitus , nausea , and vomiting .\ncurrent study clearly indicates that hypertension can be associated with cervical spondylosis , as a secondary condition .\nwe speculate that the mechanisms of hypertension induced by cervical spondylosis could be the same as that of cervical vertigo .\nit is well known that cervical disc , dura mater , and posterior longitudinal ligament are rich in sympathetic fibers .\nsympathetic nerve fibers distributed around the vertebral artery have been implicated in the autoregulation of vertebrobasilar artery blood flow and cerebral blood flow .\nit has been evidenced that sympathetic nerve activity withdraws the blood flow , whereas sympathectomy can increase it .\na previous study investigated sympathetic and parasympathetic changes incited by the stimulation of nerves around the proximal vertebral artery in cat model and found subsequent papillary changes , pulse and blood pressure changes .\nelevation in levels of inflammatory cytokines has been detected in painful discs of humans , and thought to be related to degeneration and pain . the pathogenic change in the painful disc\nis featured with the formation of zones of vascularized granulation tissue and extensive innervation extending from the outer layer of the annulus fibrosus into the nucleus pulposus .\ndegenerative changes in the disc , such as loss of the normal structure and a mechanical load , can lead to abnormal motion , which can provoke mechanical stimulation .\nmechanical stimuli , which are normally innocuous to disc nociceptors can , in certain circumstances such as inflammation , generate an amplified response termed peripheral sensitization .\nthe vertebral arteries are mainly innervated by nerve fibers from the cervical sympathetic ganglia ( 13 ) .\ninnervation in cervical disc is analogous to that in the lumbar spine , receiving innervation posteriorly from the sinuvetebral nerves , laterally from the vertebral nerve , and anteriorly from the sympathetic trunks .\nrecently , an animal study revealed a reciprocal neural connection between cervical spinal and sympathetic ganglia .\nit seems likely that stimulation of sympathetic nerve fibers in the pathologically degenerative disc and surrounding tissues produce sympathetic excitation , and induce a sympathetic reflex to cause vertebrobasilar insufficiency and hypertension .\nimprovement of neurological function , resolution of vertigo , and recovery of blood pressure following surgery could be attributed to the excision of degenerative and herniated cervical disc , the decompression of the dura mater and posterior longitudinal ligament , and the stabilization of degenerated segment .\nchronic neck pain is one of the major symptoms in patients with cervical spondylosis , whereas some studies have indicated that resting blood pressure levels may be elevated in patients with persistent pain . in healthy individuals ,\nthese interactions are believed to reflect a homeostatic feedback loop that helps restore arousal levels in the presence of acutely painful stimuli .\na role for baroreceptors in this feedback loop appears likely , with pain triggering sympathetically driven blood pressure increases , resulting in increased stimulation of baroreceptors , which in turn activates descending pain inhibitory pathways .\nprevious studies suggested that blood pressure / pain regulatory relationship may be substantially altered in chronic pain conditions .\na retrospective study by bruehl et al suggested that chronic pain could be associated with increased risk of hypertension .\ntheir study found that over 39% of patients with chronic pain were diagnosed with clinical hypertension , compared with only 21% of pain - free internal medicine patients .\nthey thought that chronic pain - related impairments in overlapping systems modulating both pain and blood pressure would result in a higher prevalence of clinically diagnosed hypertension in patients with chronic pain than in comparable pain - free patients .\nour study indicates a possible relation between chronic neck pain and hypertension . if chronic neck pain could lead to hypertension through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms , early treatment for resolution of chronic neck pain may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis\nwe report here 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension that were treated successfully with anterior cervical discectomy and fusion .\nstimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation , and induce a sympathetic reflex to cause cervical vertigo and hypertension .\nin addition , chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms .\nearly treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis .", "answer": "abstractcervical spondylosis and hypertension are all common diseases , but the relationship between them has never been studied . \n patients with cervical spondylosis are often accompanied with vertigo . \n anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy . \n we report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion . \n stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation , and induce a sympathetic reflex to cause cervical vertigo and hypertension . \n in addition , chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms.cervical spondylosis may be one of the causes of secondary hypertension . \n early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis .", "id": 345} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsince dental ceramic restorations have been introduced in 20 century,1 reproduction of natural appearance of teeth has been a major concern in dentistry . for metal - ceramic restorations ,\nlight reflection from an opaque porcelain layer to mask the metal substrate resulted in opaque appearance and therefore , their use in high esthetic area was limited.2 glass ceramic restorations without metal substrate induced more light transmission and accordingly , they improved the ability to reproduce the appearance of tooth structure.3 despite the esthetic advantage of glass ceramics , the demands for stronger ceramic restorations have increased . as a result\n, high strength zirconia - based ceramics combined with cad / cam technology have broadened the range of their applications in dentistry.4 however , cohesive failure of the veneering porcelain has been reported as a major drawback56 and thereby , fabricating monolithic zirconia restoration which consists of a single zirconia material without any veneering could be an alternative approach to obviate the veneering failure.7 the esthetic value of dental ceramic restorations is influenced by several factors , such as color , translucency , fluorescence , surface texture and shape.8 furthermore , the overall color of ceramic restorations can be influenced by the thickness of the ceramic , the thickness and the color of luting agent , and the color of the underlying tooth structure .\n9 several studies investigated the effect of the thickness on overall color and translucency of ceramic restorations.291011121314 changes of color and translucency may be expected when the thickness of porcelain layer changes , although the direction of color change may depend on the specific components of the ceramic systems.15 due to its inherent white and opaque appearance , monolithic zirconia can be colored in a pre - sintered state to match adjacent teeth . in a clinical situation , there could be a thickness reduction during the process of occlusal adjustment by dentists .\nhowever , there have been no reported studies regarding the changes of color and translucency as a function of changes in thickness using monolithic zirconia .\nthe purpose of this study was to evaluate the effect of the amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics .\nthe null hypothesis to be tested was that there was no significant difference in color and translucency between monolithic zirconia ceramics with different amount of thickness reduction .\none - hundred sixty - five square - shaped specimens from presintered yttria - stabilized tetragonal zirconia blocks ( lot no . : b 105566 , b 105583 , b 105565 , b 88712 ; bruxzir , glidewell laboratories , newport beach , ca , usa ) were colored with coloring liquid ( lot no . : 40127 , 40129 ; tanaka zircolor , a2 , tanaka dental , skokie , il , usa ) and assigned to 5 groups according to the number of coloring liquid application ( group i ( one time ) to v ( five times ) , n = 33 per each group ) following the same protocol used in our previous study.7 the specimens were heated in a furnace ( austromat basic , dekema dental - keramikfen gmbh , freilassing , germany ) with a step sintering procedure ; sintering at 950 for 10 minutes and at 1,500 for 2 hours .\nafter sintering , the thickness adjustment was performed in the same manner as was used in our previous studies.716 accordingly , the final dimensions of the specimens were 16.3 mm 16.3 mm 2.0 mm .\neach group was then divided into eleven subgroups ( n = 3 per each subgroup ) by reducing the thickness of 0.1 to 1.0 mm in increments of 0.1-mm on the colored surface using a horizontal grinding machine ( hrg-150 , am technology , asan , korea ) ; subgroup 0 ( no reduction ) , subgroup 1 ( 0.1 mm reduction ) to subgroup 10 ( 1.0 mm reduction ) .\ncolor parameters were obtained from cie - lab ( commission internationale de l'eclairage l , a , b ) color space relative to d65 on a reflection spectrophotometer ( cm-3500d , konica minolta , tokyo , japan ) . for the instrument ,\ndiffuse illumination was used and the reflected light was measured ( cie diffuse/8-degree ) at the center and each quarter of the specimen . a 3-mm diameter aperture for diffuse illumination and 3-mm measurement area\neach of l , a and b values was measured against a black background ( cm - a 101b , konica minolta , tokyo , japan , l = 0.1099 , a = 0.2107 , and b = -0.4292 ) and a white background ( cm - a120 , konica minolta , tokyo , japan , l = 96.6880 , a = -0.1755 , and b = -0.1236 ) in the reflectance mode with specular component excluded ( sce ) at 10 nm intervals in the wavelength range of visible light , 400 - 700 nm .\noptical contact was obtained by placing a drop of distilled water ( refractive index : 1.33 , approximately ) between each specimen and a background.11 spectral reflectance against a white background was recorded at 10 nm intervals in the range of 400 to 700 nm . color difference between each subgroup was calculated using cie lab color - difference formula17 denoted by eab = [ ( l ) + ( a ) + ( b ) ] .\nl , a , and b refer to the difference on lightness , red / green axis , and yellow / blue axis , respectively . to determine the color difference , the average cie values against a black background were used . for translucency measurements , translucency parameter\ntp value was calculated by the color difference between values against a black and a white background18 which is denoted by tp = [ ( lb - lw ) + ( ab - aw ) + ( bb - bw ) ] .\ndiffuse transmittance measurement was performed using an integrating sphere with the aperture size of 9.5 mm in diameter .\nall measurements , therefore , were made at the center and each quarter of the specimen and values were averaged .\n, chicago , il , usa ) and the level was set at 0.05 .\nnormal distribution of each color value and tp value was verified with shapiro - wilk test . to identify\nif there is any significant difference in color and tp values among subgroups , one - way anova was carried out followed by multiple comparison scheff test .\npearson correlation and linear regression was fitted to test for a relationship between the amount of thickness reduction and color and tp values .\n3 showed means of cie l , a and b values of each group against a black background in the reflectance mode as a function of the amount of thickness reduction , respectively .\ncie a value generally increased , while cie b value decreased with the increase of thickness reduction in all groups .\ncorrelation analyses between l , a or b values against a black background in the reflectance mode and the amount of thickness reduction were conducted .\nthere were negative , but weak correlations between l value and the amount of thickness reduction in most groups ( -0.58 < r < 0.34 , 0.09 < r < 0.34 ) .\nthere were positive correlations between a value and the amount of thickness reduction in all groups ( 0.72 < r < 0.85 , 0.52 < r < 0.73 ) .\nthere were negative correlations between b value and the amount of thickness reduction in all groups ( -0.86 < r < -0.07 , 0.00 < r < 0.74 ) .\naverage spectral reflectance curves against a white background of each subgroup within groups were obtained ( fig .\n4 ) . there was a significant difference between subgroup 0 and other subgroups through the entire spectrum and the values of spectral reflectance in other subgroups were lower than subgroup 0 .\nthe interpretation of the color difference for this study is based on the visual matching study of johnston and kao19 who found that color difference of 3.7 eab unit was acceptable for resin composites .\ncolor differences between subgroup 0 and other subgroups were clinically perceptible ( eab > 3.7 ) ( fig . 5 )\ncolor differences between subgroup 1 and 2 were within the range of perceptibility threshold ( eab < 3.7 ) except group ii .\ncolor differences between subgroup 2 and 3 were within the range of perceptibility threshold except group v. color differences between subgroup 3 and 4 , 4 and 5 , 5 and 6 , 6 and 7 , 7 and 8 , 8 and 9 , 9 and 10 were within the range of perceptibility threshold in all groups .\nmeans of tp for each subgroup within groups are calculated and ranged from 2.27 to 5.34 ( table 1 ) .\nhighly significant correlations were found out between tp values and the amount of thickness reduction in all groups ( r > 0.94 , r > 0.89 , p < .001 ) .\nspectral transmittance of each subgroup exhibited similar spectral behavior through the entire spectrum and transmittance generally increased with increasing the amount of thickness reduction in all groups ( fig .\naccording to the results of this in vitro study , the null hypothesis could be rejected because there were significant differences in l , a or b values and tp values between monolithic zirconia specimens with different amount of thickness reduction .\nthe effect of various changes in thickness of each layer on the final appearance of layered metal - ceramic structures has been studied.212152021 l value substantially increased with the decrease of porcelain thickness212 and the direction of color changes were dependent on porcelain shade and the type of metal - ceramic alloy .\nincreasing the thickness of dentin porcelain produced more scattering and absorption of the incident light and less light reflected back from the opaque layer .\nwith regard to all - ceramic systems , l value generally decreased due to increased absorption of incident light with thicker specimens , while a and b values increased as the ceramic thickness increased.101113 there might be a difference in the amount of light reflection at the opaque core between all - ceramic systems with different core translucency .\ndouglas and przybylska2 demonstrated that the semi - translucent all - ceramic systems were less affected by reduced porcelain thicknesses compared to metal - ceramics . in this study ,\nthe changes in l value showed a different feature compared to metal - ceramic or all - ceramic systems .\nthere was a significant decrease in l value at initial reduction , but there were no further significant changes on l value in most groups ( fig .\n1 ) . the different aspect of change might come from different optical and structural properties since monolithic zirconia ceramic is polycrystalline monolayer without any veneering .\nit can be inferred that there might be reduced scattering due to the reduced thickness which induces lower l value at first 0.1 mm reduction . however , as the thickness reduction proceeds , monolithic zirconia itself could act as an opaque core and induce internal reflection.22 thus , reduced reflection might compensate increased internal reflection and l value could be relatively stable .\nchromatically , a value increased , while b value generally decreased with increasing thickness reduction . regarding the shift in chroma ,\nb value was more sensitive to the change of thickness than a value showing minimal shifts in a value .\n21113 according to the study of douglas and brewer,23 dental observers were more sensitive and critical to the color difference in redness than yellowness for metal - ceramic crowns .\nhowever , their study was conducted with metalceramic crowns and therefore , further study should be performed to determine whether there is any difference in subjective color assessment between a and b value for monolithic zirconia restorations .\n3 ) , group ii exhibited noticeable changes in a and b values down to 0.2 mm reduction and group iii ; to 0.3 mm reduction , group iv ; to 0.6 mm reduction , and group v ; to 0.5 mm reduction .\nthere was no distinct difference in a and b values between groups after around 0.6 mm reduction .\nit can be inferred that the more coloring liquid is applied , the deeper the coloring liquid infiltrates .\nin addition , one time of coloring liquid application might infiltrate 0.1 mm deep through monolithic zirconia specimen , two times of application ; 0.2 mm deep , three times of application ; 0.3 mm deep , and four or five times of application ; around 0.6 mm deep through monolithic zirconia specimen .\nthis study exhibited a perceptible color difference from no reduction ( eab > 3.7 ) even after first 0.1 mm reduction regardless of the number of coloring liquid applications .\nantonson and anusavice14 investigated the translucency of dental core and veneering ceramics as a function of ceramic thickness .\nthere was a positive linear correlation between contrast ratio and thickness ( r > 0.81 ) .\nhefffernan et al . investigated the effect of the thickness of core materials,24 and the thickness of veneered core materials25 on the translucency of the specimens .\no'keefe et al.26 suggested that the thickness of the porcelain veneer was the primary factor affecting light transmission and not the opacity .\ntp values generally increased as the amount of thickness reduction increased in all groups ( r > 0.89 , p < .001 ) . based on lambert 's law,27 decreasing the thickness of material\nthe fraction of incident light that is reflected , absorbed , and transmitted depends upon the thickness of the specimen as well as the scattering and absorption characteristics.28 this in vitro study has several potential limitations .\nthe first limitation is that even application of coloring liquid on the specimens and exact amount of the increase of coloring liquid were difficult to control .\nsecondly , possible pressure fluctuation inside the furnace during the sintering process might have induced uneven color of the specimens .\nthirdly , the aperture diameter of spectrophotometer for reflectance measurement was 3 mm and possible edge loss would have affected the color measurement .\nfinally , this study was conducted with limited color of shade a2 and with a specific kind of monolithic zirconia system and coloring liquid .\ntherefore , the influence of varied color combinations with different monolithic zirconia systems should be further studied .\nincreasing thickness reduction reduces lightness and increases a reddish , bluish appearance , and translucency of monolithic zirconia ceramics .", "answer": "purposethis study investigated the effect of amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics.materials and methodsone - hundred sixty - five monolithic zirconia specimens ( 16.3 mm 16.3 mm 2.0 mm ) were divided into 5 groups ( group i to v ) according to the number of a2-coloring liquid applications . \n each group was then divided into 11 subgroups by reducing the thickness up to 1.0 mm in 0.1-mm increments ( subgroup 0 to 10 , n=3 ) . \n colors and spectral distributions were measured according to cielab on a reflection spectrophotometer . \n all measurements were performed on five different areas of each specimen . \n color difference ( e*ab ) and translucency parameter ( tp ) were calculated . \n data were analyzed using one - way anova and multiple comparison scheff test ( =.05).resultsthere were significant differences in cie l * between subgroup 0 and other subgroups in all groups . \n cie a * increased ( 0.52` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynergistic catalysis: cis-cyclopropanation of benzoxazoles\n\nPaper sections:\nIntroduction\nIn the last years huge efforts have been made to develop new activation modes in order to synthesize complex scaffolds in an enantiopure form. The most common approach has been the development of new catalysts to activate an \"unreactive\" compound A that will react with a highly reactive compound B to render C. However, recently a new approach pushes the boundaries of organic chemistry: synergistic catalysis, where the concurrent activation of both reactants allows the use of both unreactive substrates to form a new C-C bond. Earlier examples of synergistic catalysis merging transition metals and organocatalysts can be found in the pioneering works of Cordova who reported the a-allylic alkylation of unactivated aldehydes with allyl acetates by using both enamine and Pd chemistry. 1 Later, Zhang reported an efficient asymmetric variant by using Cordova's synergistic strategy and Pd catalysts with C 2 -symmetrical chiral metallocene ligands. 2 MacMillan and Sibi reported examples of asymmetric synergistic catalysis based on enamine catalysis and metal-bound electrophiles. 3 On the other hand, synergistic catalysis with a,b-unsaturated carbonyl compounds has attracted much recent interest. The works of Cordova in b-silylation, b-arylation or b-borylation by using iminium and transition-metal activation demonstrated the importance of this approach. 4 In this area, List also reported excellent results for allylation and Overman rearrangement reactions by using phosphoric acid derivatives and transitionmetal catalysts. 5 Very recently, our research group became interested in synergistic catalysis. 6 Our research focuses on the development of methodologies for the stereoselective synthesis of alkyl benzoxazoles based on the concurrent activation of alkyl benzoxazoles by metal-based Lewis acid catalysis (inspired by the pioneering work of Lam) 7 and organocatalytic activation of several electrophiles. 8 It is well known that one of the most important concerns of this approach is the possible autoquenching of both catalysts. However, by careful choice of the catalysts and the reaction conditions, we successfully developed the addition of alkylbenzoxazoles to Morita-Baylis-Hillman (MBH) carbonates and enals in good yields and stereoselectivities (Fig. 1).
Despite signi\ue103cant progress and the advantages of using two unreactive substrates, synergistic catalysis presents a clear limitation in terms of range and scope: all these reactions generate only 1 C-C bond, making this approach more expensive and contrary to atom economy (2 catalyst for only 1 bond formation). This drawback attracted our interest and we propose to overcome this limitation by a carefully designed cascade reaction based on a synergistic approach. In our earlier examples we successfully combined metal Lewis activation of azaarenes with iminium catalysis, with good results but with some limitations such as moderate enantioselectivities and low diastereoselectivities due to an epimerization process. 6b We thought that a good option to develop a cascade reaction based on a synergistic approach and, at the same time, to limit the drawbacks of our previous work, should be the design of an organocascade reaction that could trap the enamine \"in situ\", rendering a more complex scaffold with high stereoselectivity using the same catalytic system in order to push the boundaries of synergistic catalysis by forming 2 C-C bonds using 3 catalytic cycles.
Due to our experience in organocascade reactions, we envisioned that a cyclopropanation using chloro-alkylbenzoxazoles and enals will ful\ue103l the requirements as a proof of concept of this approach and at the same time will allow us to synthesize an important scaffold in organic chemistry.
Cyclopropanes 9 are structural motifs widely present in naturally occurring compounds, including terpenes, fatty acid metabolites, pheromones, etc., 10 and in pharmaceutical compounds with a large spectrum of biological properties. 11 Cyclopropanes are also useful as synthetic intermediates that can undergo ring-opening or ring-expansion reactions to form a range of functionalized products. 12 Asymmetric cyclopropanation reactions have fascinated organic chemists for decades and exciting advances have recently been reported; however, the development of new methodologies for the stereoselective synthesis of cyclopropanes is still a major challenge. In the literature, several approaches for their enantioselective synthesis are reported, for example, the venerable Simmons-Smith cyclopropanation, 13 organometallic methodologies that use Cu, Rh and other transition-metal complexes 14 or, with the advent of organocatalysis, several Michael-initiated ring-closing domino reactions, etc. 15
\n\nResults and discussion\nTo show the viability of the present reaction initially we studied the addition of chloro-alkylbenzoxazole 1a with cinnamaldehyde. The proposed synergistic mechanism is shown in Fig. 2.
As shown in Fig. 2, we envisioned that the metallic Lewis acid would interact with the alkylbenzoxazole 1 by coordinating to the nitrogen atom of 1 and increasing the acidity of the proton in the methylene position. The co-catalyzed mechanism involves the stereoselective addition of palladium enolate (9) to chiral iminium intermediate 6, followed by an intramolecular 3exo-tet cyclization. As suggested by Lam, 7 at \ue103rst a coordination of the palladium to the benzoxazole occurs, followed by deprotonation by the external base leading to species A\ue09der a short screening we found that the best conditions were MeCN as a solvent, Pd(OAc) 2 as a Lewis acid, Jorgensen-Hayashi catalyst (I) as secondary amine and 2,6-lutidine as stoichiometric base. To our delight the reaction rendered the \ue103nal cyclopropane rings in excellent yields and stereoselectivities. The study of NMR spectra con\ue103rmed that the major diastereomer obtained in the cyclopropanation reaction has a cis disposition between the aryl ring and the benzoxazole substituent (see ESI \u2020). This result adds, without any doubt, an important value to the present methodology. The synthesis of cis di(hetero)aromatic cyclopropanes via an intermolecular reaction is very challenging. This unusual cis con\ue103guration is difficult to obtain by any other enantioselective methodology that forms the C-C bond bearing both aryl groups. Only Mezzetti 16 and Katzuki 17 using ruthenium and iridium catalyst got the cis compound as a major diastereomer with excellent results in the reaction of styrenes with diazoacetates. Formally, the methodology reported in this paper is stereocomplementary with the MacMillan cyclopropanation that renders trisubstituted cyclopropanes in a trans con\ue103guration. 18 With the optimized reaction conditions in hand, we investigated the substrate scope of the reaction with respect to enal derivatives. As shown in Scheme 1, the reactions afford the corresponding formyl cyclopropanes in good to excellent yields with moderate to good diastereoselectivities and excellent enantioselectivities in the major diastereomer. Remarkably, in all the examples the major diastereomer could be easily isolated by column chromatography while the other two diastereomers observed, usually are non-separable mixtures. All the diastereomeric ratios are from the \ue103nal isolated products.
The reaction is compatible with several substituents in the aromatic ring. Electron-withdrawing groups like 4-NO 2 (4d) or 4-CN (4f) render the \ue103nal cyclopropane in good yields (79% and 63%), good diastereoselectivities and excellent enantioselectivities. Several halides were also tested in the reaction giving similar results, for example 4-Br (4b), 4-Cl (4c) and 4-F (4e) render the predicted formyl cyclopropane in good yields and diastereoselectivities (86-70% yield and up to 3 : 1 d.r.) and exceptional enantioselectivities (up to 99% ee). When the most sterically demanding 2-Br cinnamaldehyde derivative was used, the formyl cyclopropane (4h) was obtained with good yields and excellent enantioselectivity in the major diastereomer but with lower diastereoselectivity. To our delight, when we tested the enal derived from glyoxylate, the reaction rendered the cyclopropane (4i) with good yield and excellent diastereoselectivity (only one diastereomer) but lower enantioselectivity. This could be due to an epimerization at C3 position of the product during the reaction.
As shown in Fig. 3, when an ester moiety is placed in C3, this proton becomes quite acidic and could undergo epimerization with the base to form the most stable trans diastereomer, which would be stabilized by a coordination of the metal with the nitrogen from benzoxazole and the carbonyl compound from the ester. If this epimerization occurs, the outcome of the reaction will be one diastereomer with moderate enantioselectivity as observed by us. Finally, the only limitation of the present methodology is with the aliphatic enals that gave complex crude mixtures when subjected to the reaction conditions.
The relative con\ue103guration of the minor diastereomer was con\ue103rmed by X-ray crystallography (Fig. 4), while the relative con\ue103guration of the major diastereomer was inferred by NMR spectroscopy (see ESI \u2020).
The absolute con\ue103guration of the two diastereomers was determined to be 1R,2R,3S for the major diastereomer 4d (using (S)-I as catalyst) and 1R,2R,3R for the minor diastereomer 4d 0 (using (R)-I as catalyst) by TD-DFT simulation of the Electronic Circular Dichroism (ECD) spectra (Fig. 5 and ESI \u2020). 19 This absolute con\ue103guration and diastereoselectivity of the major diastereomer is in agreement with the mechanism proposed and with the previous works done with this type of catalysts, where the stereochemistry at b-position of the enal is perfectly controlled by catalyst (I). 15 The relative and absolute con\ue103guration of the minor diastereomer could be rationalized by the reaction with the (Z)-palladium enolate.
Next, we investigated the substrate scope of the reaction with respect to the benzoxazole derivative 1. Several benzoxazole derivatives were tested (Scheme 2) and the presence of electronwithdrawing groups in the azaarene ring was crucial for the reactivity. Cl-substituted benzoxazole rendered the \ue103nal product 5a, 5e and 5f with good yields, good stereoselectivities and excellent enantioselectivities. When the benzoxazole had a -NO 2 group at a different position (5b and 5d), slightly lower yields were observed but good diastereoselectivities and excellent enantioselectivities were obtained. Finally, changing the electron-withdrawing -NO 2 group to an ester group rendered the \ue103nal product 5c in excellent yield, good diastereoselectivity and excellent enantioselectivity. The only limitation, as previously noted in our previous reports on synergistic catalysis, 6a,b is that an electron-withdrawing group must be present on the benzoxazole ring. Probably, the electron-withdrawing group decreases the pK a value of 1 and allows the deprotonation and the subsequent reaction.
\n\nConclusions\nIn summary, we have demonstrated that synergistic catalysis can be applied to the development of a cascade reaction by developing a highly enantioselective cyclopropanation of enals with chloro-alkylbenzoxazoles. For the \ue103rst time, the metal activation of azaarenes was combined with an organocatalytic cascade reaction, pushing the boundaries of this synergistic approach. Two different catalytic cycles, (i) the metallic Lewis acid activation of azaarenes and (ii) the secondary amine activation of enals, worked in accord to afford the \ue103nal products in good yields, with excellent enantioselectivity and good diastereoselectivity. Moreover this reaction gives access to cis cyclopropanes that are difficult to obtain by any other method. The mechanistic studies, synthetic applications and development of new organocascade reactions based on this concept are currently ongoing in our laboratory.
", "answer": "In the present paper we report our latest efforts in pushing the boundaries of synergistic catalysis. We propose the use of 3 different catalytic cycles working in concert for the formation of cis cyclopropane derivatives of benzoxazoles with excellent stereoselectivities. This is the proof of concept that synergistic catalysis could be successfully used in cascade reactions.", "id": 365} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynthesis and evaluation of cyclic sulfite diesters as sulfur dioxide (SO2) donors\n\nPaper sections:\nIntroduction\nSulfur dioxide (SO2) is an environmental pollutant that is also produced during metabolism of sulfur containing amino acids [1] as well as hydrogen sulfide (H2S), which is known to mediate a number of cellular processes. [2] The known vasodilatory effects of SO2 in animal models suggest possible signaling roles for this gas as well. [3] SO2 is also used in the food industry as a preservative and an anti-bacterial agent. [4] At elevated levels SO2 is known to cause biomacromolecular damage and cell death; [5] these damaging effects are perhaps responsible for the anti-bacterial properties of this gas. However, due to the limited understanding of molecular mechanisms of action of this gas, reliably producing [6] and detecting SO2 within cells are necessary. While there are numerous probes for SO2, biological studies have thus far relied on gaseous SO2 or a complex formulation of inorganic sulfites. [7] Both methods may not be well suited for enhancing SO2 within cells and offer no temporal control over SO2 release. Furthermore, they are useful for studying effects of SO2 as a single dose, which is unsuitable for study of prolonged exposure. Thus, the chemical biology of SO2 remains largely uncharacterized. 15 Our laboratory has developed several strategies having different triggers for generating SO2 under physiological conditions using small organic molecules. [8] First, 2,4-dinitrophenylsulfonamides with tunable rates of generation of SO2 when triggered by biological thiols were reported (Scheme 1). The use of thiol is used as a trigger may complicate biological studies as targets of SO2 include biologically relevant disulfides and thiols. [8a, 8b, 9] In a second strategy, a series of benzosultines as SO2 donors with controlled rate of generation of SO2 under physiological condition, having heat as a trigger was reported (Scheme 1). [8c] Although enzosultines are stable as solids, they are not highly suited for prolonged storage at room temperature as stock solutions. In third strategy, benzosulfones were reported as photochemically activated SO2 donors by our group and others (Scheme 1). [8d] These compounds might have limitations associated with the inconvenience associated with using a light source in cellular studies and possibly by intensity of light that was required for SO2 generation. [10] Xian et al. reported sodium benzothiazole sulfonate as water-soluble SO2 donor, having limitation of prolonged half-life (t1/2 = 13 days) at physiological pH 7.4. [11] Recently, SO2 donors, using esterase as a trigger, [8f, 12] and click reaction as a mode of SO2 donation, have been reported by our, and Wang's group (Scheme 1). These strategies rely on the use of cellular enzyme, and bio-orthogonal reaction.
Scheme 1. Reported strategies for generation of SO2 under physiological conditions.
Therefore, new self-emulative SO2 donors which are stable at room temperature and permeate cells to enhance intracellular SO2 could help better understand cellular responses to this important gaseous molecule.
\n\nResults and Discussion\n1,2-Cyclic sulfite diesters were considered as SO2 donors (Scheme 2). Upon attack by a nucleophile (such as water), a sulfite monoester would be formed, which could spontaneously decompose to produce SO2. Modulating substituents \"R\" or perhaps the pKa of the leaving group would help tune the rate of substitution by a nucleophile and possibly SO2 release. Here, we report results of synthesis and evaluation of a series of 1,2-cyclic sulfite diesters as SO2 donors. 1,2-diols used for synthesis of 1,2-cyclic sulfite diesters were either commercially available (1 and 2; Figure 1) or prepared by Upjohn dihydroxylation from corresponding olefin by OsO4 mediated dihydroxylation [13] (diols 3-5 and 11; Figure 1) or by nucleophilic ring opening of 4-substituted styrene oxide by 10% aq. K2CO3 solution. The diol 6 and 10 were synthesized from Ltartaric acid, and NaBH4 mediated reduction [14] of (\u00b1)-benzoin respectively. The diols 7 and 8-9 were prepared by ring opening of corresponding (\u00b1)-phenyloxirane and substituted (\u00b1)phenyloxirane, in 10% K2CO3 reflux condition respectively. Various 1,2-cyclic sulfite diesters (12-22) were prepared by the reaction of 1,2-diols with thionyl chloride, triethylamine and imidazole in DCM at 0 \u00b0C (Table 1). [15] The cis-1,2-diols 3 and 4, gave an isomeric mixture (depending on sulfoxide orientation) of 14 (1:0.68), 15 (1:0.64) by 1 H NMR. [16] The diols 5, 6 and 11 afforded mixture of diastereomers of 16, 17 and 18 in the ratios (depending on chirality of sulfoxide), 16 (1:0.95), 17 (~1:1) and 22 (1:0.86) by 1 H NMR. The racemic 1,2-diols 7-10 afforded mixture of diastereomers for 18-21.
The aforementioned derivatives 12-22 were evaluated for SO2 release in pH 7.4 phosphate buffer. First, ethylene glycol derivative 12 was incubated at 37 \u00b0C in pH 7.4 buffer for 30 min. The reaction was monitored for SO2 generation by ion chromatography equipped with an ion conductivity detector; [8b] SO2 was quantified as sulfite, SO3 2-. After 30 min, 12 gave 45% of SO2 (Table 2, entry 1). The pinacol derivative 13 produced negligible amounts of SO2 and a 2% yield was recorded (Table 2, entry 2). These results suggest that increasing sterics on the carbon bearing the sulfite functional group reduced the propensity for decomposition of the compound supporting direct displacement at the carbon, which involves formation of a sulfite monoester, which in turn rapidly rearranges to produce SO2 and an alcohol (Scheme 2) Scheme 1. Sulfite diesters can decompose in pH 7.4 buffer to produce SO2. In the cases of 12-15, nearly similar pKa values for the alcohols implies that any difference in SO2 yields must be due to increased steric hinderance at the carbon bearing the sulfite ester. The diesters 12, 14 and 15 gave SO2 yields > 20% after 30 min, whereas pinacol derivative 13 gave 2% of SO2. These results suggest that when leaving group was similar the important determinant of observed reaction rates was sterics supporting the proposed mechanism (Scheme 2). These results are also consistent with previous reports [17] of 1,2-cyclic sulfite diesters undergoing nucleophilic substitution with various nucleophiles such as chloride, azide and (CH3OOC)2HC \u2212 at one of the activated carbon atoms (Scheme 2). [17][18] The hydrolysis of cyclic sulfite esters of normal, or cis or trans diols under acidic (cat. H2SO4/HClO4) or basic (2 eq. NaOH) reflux condition, results in sulfur-oxygen bond fission to give corresponding diol without change in stereo-configuration. [17,19] In order to study the electronic effect on decomposition, diesters 16 and 17 were incubated in pH 7.4 buffer and 93% and 98% SO2, respectively were recorded (Table 2, entry 5 and 6). These compounds contain an electron withdrawing substituent as compared to ethylene glycol diester 12. The electron withdrawing nature of the ester enhances electrophilicity of the carbon bearing the sulfite functional group contributing to an increased rate of displacement.
Next, decomposition of derivatives with phenyl substituent 18-21 was carried out. After 30 min, the phenyl derivative 18 gave 73% of SO2 (Table 2, entry 7). The 4-NO2-phenyl derivative 19 on the other hand produced higher amount of SO2 and a 96% yield was obtained (Table 2, entry 8). Incubation of the 4-F-phenyl derivative 20 (Table 2, entry 9) resulted in a nearly similar SO2 yield as that of phenyl derivative 18. The diphenyl derivative 21 gave 83% SO2 after 30 min (Table 2, entry 10). These results suggest that electron withdrawing group on phenyl substituent increases the rate of decomposition, again consistent with a nucleophilic displacement mechanism. Values are for the corresponding 1,2-diol (most acidic proton) calculated using ChemBioDraw Ultra 16.0.
A number of SO2 probes that typically use the distinct nucleophilic properties of sulfite/bisulfite have been developed by various groups. [20] . For example, Sun et al. have reported probe 23 for selective detection of SO2 derivatives HSO3 -/SO3 2in pH 7.4 buffer (Scheme 3). [20c] The probe 23 absorbs at 545 nm and upon reaction with HSO3 -/SO3 2-, a distinct and ratiometric shift to an absorbance at 410 nm (for 24) was observed (see Supporting Information, Figures S1 and S2). A similar UV profile was observed when 23 was reacted with the SO2 donor 17 supporting the intermediacy of sulfite (Figure 2a). The probe 23 fluoresces in the red region and upon reaction with SO3 2-/HSO3it forms green fluorescing adduct 24 (Figure 2b). When 23 was treated with sulfite diester 17, we find a similar shift in emission (Figure 2b). Together, these data independently confirm the ability of 17 to generate SO2 in pH 7.4 buffer.
\n\nScheme 3. Reaction of probe 23 with sulfites\nThe expected product formed during hydrolysis in buffer is the diol (Scheme 2). In order to confirm this, we incubated 19 in pH 7.4 buffer and monitored the decomposition and formation of 1-(4-nitrophenyl)ethane-1,2-diol 8 (Figure 3). We find nearly complete disappearance of 19 during 30 min with the formation of 8 as the exclusive product (Figure 3) and a nearly quantitative yield of SO2 (Table 2, entry 8). Thus, the decomposition of the sulfite monoester was and SO2 is likely to be generated as soon as the intermediate is produced (Scheme 2). Having established the suitability of cyclic sulfite esters for molecular biology studies, cell permeability as well as the suitability of these compounds for enhancing intracellular levels of SO2 was examined. The ratiometric probe 23 has been previously reported to be suitable for detection of intracellular sulfite/bisulfite. When DLD-1 cells treated with 23 (10 \u03bcM), we found a distinct fluorescence signal only in the red channel but not in the green channel (Figure 4A-C). [20c] When cells pre-treated with 23 were exposed to 17 (20 \u03bcM), a decrease in fluorescence signal in the red channel with concomitant increase in fluorescence increase in green channel was observed (Figure 4D-F). Under similar conditions, when a similar experiment was conducted with authentic bisulfite, we found a similar profile. [20c] However, an increased concentration of 200 \uf06dM was necessary to elicit this response whereas with the donor developed in this study, a significantly lower concentration could achieve enhancement of intracellular SO2. Above results suggest the compatibility of cyclic sulfite diesters with cellular nucleophiles. Lastly, a cell viability assay conducted with human cervical cancer cells (HeLa) revealed SO2 donors 17 and 13 were not significant inhibitors of proliferation at 100 \u03bcM (see Supporting Information, Figures S3 and S4). Thus, the SO2 donor 17 might find convenient use for studying cellular responses to enhanced reactive sulfur species.
\n\nConclusions\nIn summary, we report a series of 1,2-cyclic sulfite diesters that: can be easily synthesized; are stable at room temperature; have tunable SO2 release profiles; and are well suited to study effects of enhanced intracellular levels of SO2 and duration of exposure to this reactive species. Together, we present superior alternatives to inorganic sulfites, the most commonly used SO2 donors. Due to the fundamental importance of redox regulation in cellular growth and survival, perturbation of redox homeostasis has emerged as a possible mechanism for the development of new therapeutics. [21] Thus, reliably generating reactive oxygen, [22] nitrogen [23] and sulfur species [8a, 8b, 8e] may have a range of applications including developing small molecule-based inhibitors of against bacteria such as Staphylococcus aureus, [8e, 22e] Mycobacterium tuberculosis [8a, 8b, 22a, 22b] as well as cancer. [24] Experimental Section Synthesis and characterization data for all new compounds and assay protocols.
", "answer": "Although sulfur dioxide (SO2) finds widespread use in the food industry as its hydrated form, sulfite, a number of aspects of SO2 biology remain to be completely understood. Among the tools available for intracellular enhancement of SO2, most suffer from poor cell permeability and a lack of control over SO2 release. We report 1,2-cyclic sulfite diesters as a new class of reliable SO2 donors that dissociate in buffer through a nucleophilic displacement to produce SO2 with tuneable release profiles. We provide data in support of the suitability of these SO2 donors to enhance intracellular levels of SO2 at an efficiency superior to sodium bisulfite, the most commonly used SO2 donor for cellular studies.", "id": 366} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe relationship between pulp of the tooth and surrounding periodontium was first described in 1964 , and since then the term endo - perio has become an integral part of the dental vocabulary . unfortunately , this term has been used indiscriminately to categorize disease of either periodontal or endodontic etiology , with or without secondary involvement of the other .\nit conveniently provides a blanket diagnosis but could be misleading for any such lesion , regardless of its primary etiology .\nalthough the role of pulpal pathology in the etiology of furcation involvement is still unclear , the high incidence of molar teeth with accessory canals supports such an association .\nvarious treatment modalities have been proposed for the treatment of furcation involvement alone including open flap debridement , bio - modification of root surface , and various regenerative procedures including gtr and bone grafts .\nbone grafts having a property of osteogenesis , osteoinduction , and osteoconduction have been used in the past .\nthis case report attempts to utilize a bioactive glass with the property of osteostimulation as bone replacement graft in the treatment of a combined endo - perio lesion with furcation involvement .\nthe periodontium and pulp have embryonic , anatomic , and functional interrelationship . the relationship between pulpal and periodontal disease\ncan be traced to embryological development , since the pulp and the periodontium are derived from a common mesodermal source . at the stage of tooth development\n, the developing tooth bud pinches off a portion of mesoderm that becomes pulp , while the remaining mesoderm develops into the periodontium .\nectomesenchymal cells proliferate to form the dental papilla and follicle , which are the precursors of the periodontium and the pulp , respectively\n. this embryonic development may give rise to an anatomical connection between these two vital structures throughout the life of a tooth .\nthree main pathways have been implicated in the development of periodontal - endodontic lesions , namely : \n dentinal tubuleslateral and accessory canalsapical foramen \n lateral and accessory canals the most commonly used classification was given by simon et al . \n\nprimary endodontic lesionprimary periodontal lesionprimary endodontic lesion with secondary periodontal involvementprimary periodontal lesion with secondary endodontic involvementtrue combined lesion \n primary endodontic lesion primary periodontal lesion primary endodontic lesion with secondary periodontal involvement primary periodontal lesion with secondary endodontic involvement\nthe periodontium and pulp have embryonic , anatomic , and functional interrelationship . the relationship between pulpal and periodontal disease\ncan be traced to embryological development , since the pulp and the periodontium are derived from a common mesodermal source . at the stage of tooth development ,\nthe developing tooth bud pinches off a portion of mesoderm that becomes pulp , while the remaining mesoderm develops into the periodontium .\nectomesenchymal cells proliferate to form the dental papilla and follicle , which are the precursors of the periodontium and the pulp , respectively . this embryonic development may give rise to an anatomical connection between these two vital structures throughout the life of a tooth .\nthree main pathways have been implicated in the development of periodontal - endodontic lesions , namely : \n dentinal tubuleslateral and accessory canalsapical foramen \n lateral and accessory canals\nprimary endodontic lesionprimary periodontal lesionprimary endodontic lesion with secondary periodontal involvementprimary periodontal lesion with secondary endodontic involvementtrue combined lesion \n primary endodontic lesion primary periodontal lesion primary endodontic lesion with secondary periodontal involvement primary periodontal lesion with secondary endodontic involvement\na 22-year - old patient reported to the department of periodontics with a complaint of pain in the lower right back tooth region associated with pus discharge since 1 month . on intraoral examination , an intraoral sinus was found to be present in relation with 46 [ figure 1 ] .\na radiograph was taken with a gutta percha cone inserted in the sinus so as to gauge the path of the sinus tract as shown in figure 2 .\niopa also showed widening of periodontal ligament space in relation with the mesial root and radiolucency in the furcation area .\nthe horizontal probing depth ( hpd ) with naber 's probe and vertical probing depth ( vpd ) with the unc-15 probe were measured which were found to be 6 mm and 4 mm , respectively .\nprobing was standardized by fabricating an acrylic stent as shown in figures 1 and 3 .\nthe patient was then referred to department of conservative dentistry to check for tooth vitality .\nelectric pulp testing was done to check for tooth vitality , which confirmed that the tooth was nonvital .\nvpd of 4 mm with unc-15 probe radiograph showing gutta percha when inserted though the sinus tract extending till the mesial root of 46 hpd of 6 mm with naber 's probe treatment planning was done taking into consideration that the tooth was nonvital with a prevailing sinus tract and grade ii furcation involvement as well .\nendodontic treatment was taken up first and the patient was followed up for 3 months . at the end of third month , iopa was taken with 46 which showed that the furcation involvement still prevailed [ figure 4 ] .\non clinical examination , it was observed that there was no change in the soft tissue measurements .\ntherefore , periodontal regenerative surgery using dental putty was planned for treatment of furcation defect [ figure 5 and 6 ] . obturated 46 with radiolucency still evident after 3 month furcation defect with 46 graft material in place at the defect after taking care of asepsis and sterilization the surgery was planned . the area selected for surgery\na full thickness flap was raised at the buccal aspect following intracrevicular incision and vertical releasing incision .\na vertical releasing incision was placed extending into the alveolar mucosa not closer than one tooth to the involved area , i.e. 46 .\nfull thickness flap was raised till the base of furcation defect followed by split thickness flap beyond the mucogingival junction .\nthis was done so as to facilitate the coronal positioning of flap , there by resulting in complete coverage of the defect and the material used . after reflection thorough degranulation and debridement was done at the defect area using gracey 's curette # 13 and 14 .\nalso thorough scaling and root planning was carried out on the exposed root surface area of the defect .\ndental putty graft material with osteoconductive and osteostimulative properties was placed and stabilized in the furcation area .\nprimary soft tissue closure of the flap was done with nonresorbable black silk ( 30 ) suture using interrupted suturing technique [ figure 7 ] .\nimmediate postoperative the patient was advised proper plaque control , and was prescribed 0.12% chlorhexidine mouthwash for rinsing twice daily .\nthe sutures were removed 10 days after surgery and the patient was advised to brush at the surgical site using a postsurgical brush for 2 weeks .\nthe patient was put on regular recall at 1 , 3 , 6 , and 9 months .\nthe post - op radiograph shows bone fill in the furcation defect as shown in figure 8 .\nafter taking care of asepsis and sterilization the surgery was planned . the area selected for surgery\na full thickness flap was raised at the buccal aspect following intracrevicular incision and vertical releasing incision .\na vertical releasing incision was placed extending into the alveolar mucosa not closer than one tooth to the involved area , i.e. 46 .\nfull thickness flap was raised till the base of furcation defect followed by split thickness flap beyond the mucogingival junction .\nthis was done so as to facilitate the coronal positioning of flap , there by resulting in complete coverage of the defect and the material used .\nafter reflection thorough degranulation and debridement was done at the defect area using gracey 's curette # 13 and 14 . also thorough\nscaling and root planning was carried out on the exposed root surface area of the defect .\ndental putty graft material with osteoconductive and osteostimulative properties was placed and stabilized in the furcation area .\nprimary soft tissue closure of the flap was done with nonresorbable black silk ( 30 ) suture using interrupted suturing technique [ figure 7 ] .\nthe patient was advised proper plaque control , and was prescribed 0.12% chlorhexidine mouthwash for rinsing twice daily .\nthe sutures were removed 10 days after surgery and the patient was advised to brush at the surgical site using a postsurgical brush for 2 weeks .\nthe patient was put on regular recall at 1 , 3 , 6 , and 9 months .\nthe post - op radiograph shows bone fill in the furcation defect as shown in figure 8 .\nwhen a clinician can not make a definitive diagnosis in the case of an endo - perio lesions , it may be prudent for him or her to initiate either of the treatment modalities and hope for repair .\nhowever , this could be overcome by proper history taking and sequential treatment planning . when the etiology is purely endodontic , calcium hydroxide can be used as an intracanal medicament .\nit is an excellent medicament in general , because it is bactericidal , anti - inflammatory and proteolytic ; it inhibits resorption ; and it favors repair .\nit is especially effective in endodontic lesions with extensive periapical pathology and pseudo pockets , because of its temporary obturating action which would inhibit periodontal contamination of the instrumented canals via patent channels of communication .\nhowever , lesions which are not true combined lesions , little or no improvement would be seen with the periodontal perspective after endodontic treatment , leaving a very poor and often hopeless prognosis . but with the advent of new regenerative materials\n, however , successful periodontal treatment of such lesions has been possible . in this report the pulp vitality test which showed the nonvital nature of the tooth was a pivoting finding suggesting the primary endodontic involvement . generally , in a case of combined endo - perio lesion , an adequate endodontic therapy would result in healing of the endodontic component , and the prognosis would finally depend on the efficacy of periodontal repair / regeneration initiated by either of the treatment procedures . in this case , following endodontic treatment the periodontal lesion did reduce to an extent on radiographic evaluation after 3 months but did not subside completely with no change in the clinical parameters .\nit enhances bone formation by ionic dissolution of the ceramic particles such that the silica gel layer forms over the particles on contact with body fluids . over this silica gel layer , a calcium phosphate layer forms , which is quickly converted into a hydroxycarbonate apatite layer\nthis apatite layer has been shown to be identical to bone mineral and to provide the surface for osteoblast cell attachment and bone deposition .\nthe results of this case report suggest that bioactive glass in the form of putty resulted in a significant amount of bone fill and reduction in hpd .\nthis was in accordance with the studies by yukna et al . and anderegg et al .\nusing bioactive glass showed significant improvement in the clinical parameters when used in furcation defects .\nthe healing of an endodontic lesion is highly predictable , but the repair or regeneration of periodontal tissues is questionable if associated with it .\nendodontic therapy mostly should precede periodontal pocket elimination procedures in the case of a primary endo and secondary periodontal involvement ; however , endodontic therapy would result only in resolution of the endodontic component of involvement and would have a little effect on the periodontal lesion .\ntherefore a thorough diagnostic examination usually will indicate the primary etiology and , thereby , direct the proper course of treatment plan as presented in this case .\nit could also be concluded that bioactive glass in the form of putty which was primarily due to 21% of glycerin added to 69% of bioactive glass and 10% of poly ethylene glycol , made it feasible for manipulation of the material and effective defect fill .\ntherefore within the limits of this study it can be concluded that bioactive glass is effective as a bone graft substitute in treatment of periodontal component of the endodontic lesion .", "answer": "the success of a combined periodontal and endodontic lesion depends on the elimination of both of these disease processes . in the case of a combined endo - perio lesion , the endodontic therapy results in healing of the endodontic component of involvement while the prognosis of tooth would finally depend on the healing of the periodontal structures . \n this case report evaluates the efficacy of bioactive glass in the management of furcation defect associated with an endo - perio lesion in a right mandibular first molar . a 22-year - old male patient with an endo - perio lesion in the right mandibular first molar \n was initially treated with endodontic therapy . following the endodontic treatment , \n the furcation defect was treated using bioactive glass in a putty form . at the end of 9 months \n , there was a gain in the clinical attachment level and reduction in probing depth . \n radiographic evidence showed that there was a significant bony fill .", "id": 367} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a recent issue of critical care , morgan and colleagues present the results of a well - conducted systematic review and meta - analysis of the effect of statin therapy on inflammatory markers after cardiac surgery .\nobservational evidence suggests that statin therapy may dampen the inflammatory response following exposure to a significant trigger and there is currently much interest in using statins to treat sepsis . in this context cardiopulmonary bypass ( cpb )\nis appealing methodologically because it allows the study of preventive interventions [ 4 - 6 ] .\nfortunately for patients , mortality following cpb is low , but the methodological downside of this success is that very large trials of low risk patients ( or somewhat smaller trials of higher risk patients ) are needed to show a mortality effect .\nthe randomised controlled trials included by morgan and colleagues measured post - operative inflammatory markers in adults receiving a statin or placebo prior to cpb . they found that statin therapy may reduce post - cpb inflammation as measured by il-6 , il-8 , c - reactive protein and tumour necrosis factor - alpha .\nfor example , six of the eight apparently randomised studies provide no information on sequence generation and allocation concealment .\nthree were unblinded and only two had a low risk of bias ( defined by applying the cochrane risk of bias tool ) .\nthe median sample size was 43.5 ( range 20 to 200 ) and the confidence intervals around the mean differences in inflammatory markers for individual studies and for the summary estimates were fairly wide .\nother studies of inflammatory biomarkers are likely to vary widely between patients and within patients over time , suggesting that analysis of within - patient changes over time may detect differences between treatment groups with more statistical power .\nwhile the meta - analysis does not provide a definitive answer , it raises key methodological issues relevant to sepsis research in general , and to statin research in critical illness in particular .\nthe methodological quality of many of these studies is variable and frequently the mechanisms ( at both biological and functional levels ) through which benefit are supposed to accrue were not robustly described .\nwe agree with other authors that the logical sequence of questions to answer before performing pragmatic mortality trials should be : first , can statins theoretically beneficially modulate the immune response in these patient populations ?\nsecond , do statins beneficially ( and safely ) modulate the immune response and associated physiology ?\nthird , does the modulated immune response translate into benefit at the level of organ function ? in this regard the critical care research community can learn much from colleagues in rheumatology , cardiology and oncology , who have explored and described mechanistic pathways - paths reliably connecting biological plausibility and effect with organ performance and then outcomes important to patients ( for example , mortality ) ; and developed reliable and validated surrogate endpoints .\nmorgan and colleagues want to establish whether potential surrogate endpoints ( inflammatory markers ) are modulated , but herein lay the problems .\nsecond , while data from successful ' mortality ' randomised controlled trials may improve our understanding of surrogate outcomes , interventions that improve surrogate markers do not necessarily translate into improved mortality [ 12 - 14 ] .\nthird , what is the minimum clinically important difference for a biomarker or combination of biomarkers ? how much should individual ( and aggregate ) marker levels differ between groups to translate into clinical benefit ?\nlastly , what if ' good ' markers are also suppressed and , indeed , how much inflammation is good for you ?\nit is clear that in this relatively new study area the knowledge space is already occupied by poor studies and potentially unreliable data .\nwe would like to encourage investigators to design studies that are methodologically robust and provide reliable mechanistic data .\nicu researchers should work towards developing valid surrogate endpoints to allow robust and reliable translational research , although we acknowledge that previous success at improving organ performance has not always improved outcomes [ 12 - 14 ] .\nonce validated , these surrogate endpoints should be used to establish the biological effectiveness of new treatments ( and probably some existing ones ) before moving on to pragmatic studies using mortality as outcome measure . without demonstrating first biological and then functional ( for example , organ performance ) effectiveness , we run the risk of wrongly adding statins to the wasteland of icu pharmacotherapy . on the positive side ,\nthe pleiotropic effects of statins and extensive experience with these agents in cardiology mean that we may be less likely to fall into a trap constructed of an insufficient understating of mechanisms combined with a single - target therapy .", "answer": "statin therapy may prevent an excessive inflammatory response after cardiopulmonary bypass for cardiac surgery . in a recent issue of critical care , morgan and colleagues present data from a well - conducted systematic review and meta - analysis of randomised controlled trials using inflammatory markers as primary outcome measure . \n they find that pre - operative statin therapy , compared with placebo , may reduce various post - operative markers of systemic inflammation ( il-6 , il-8 , c - reactive protein , tumour necrosis factor - alpha ) . \n their ability to make definitive conclusions is limited , however , by the suboptimal methodological quality of the primary studies . \n their review suggests that icu researchers should focus on developing valid surrogate markers and use these to accurately describe the mechanisms and effectiveness of novel therapies before proceeding to large pragmatic trials using mortality as primary outcome .", "id": 368} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n. an earlier version of this paper was written as part of charlotte khlbrandt 's msc dissertation project at the london school of hygiene and tropical medicine .\nck conducted the literature review , collected and analysed the data , interpreted the results and drafted the paper .\nwe would like to thank dr alex mold , who co - supervised the msc dissertation and commented on a draft of this paper .\nwe are also grateful for the wellcome trust 's commitment to cover open access charges .\n. an earlier version of this paper was written as part of charlotte khlbrandt 's msc dissertation project at the london school of hygiene and tropical medicine .\nck conducted the literature review , collected and analysed the data , interpreted the results and drafted the paper .\nwe would like to thank dr alex mold , who co - supervised the msc dissertation and commented on a draft of this paper .\nwe are also grateful for the wellcome trust 's commitment to cover open access charges .", "answer": "light therapy is still used to treat a number of common diseases in russia . \n the practice is firmly anchored in history : soviet clinical practice was divorced from the emerging field of evidence - based medicine . \n medical researchers were cut off from international medical research and scientific literature , with much soviet scientific activity based on a particular socialist ideology . in this study , \n the use of light therapy serves as a case study to explore tensions between international evidence - based medicine and practices developed in isolation under the soviet union , the legacy of which is to the detriment of many patients today . \n we used four different search methods to uncover scientific and grey literature , both historical and contemporary . \n we assessed the changing frequency of publications over time and contrasted the volume of literature on light therapy with more orthodox treatments such as statins and painkillers . \n our search found an increasing number and comparatively large body of scientific publications on light therapy in the russian language , and many publications emanating from prestigious russian institutions . \n combined with our analysis of the historical literature and our appraisal of 22 full text articles , this leads us to suggest that light therapy entered mainstream soviet medical practice before the stalinist period and still occupies an important position in contemporary russian clinical practice . \n we propose that this outdated treatment survives in russia in part due to the political , economic and social forces that helped to popularize it during soviet times , and by the seeming justification offered by poorly executed studies .", "id": 369} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe protein folding problem , or the protein structure prediction problem , is one of the most interesting problems in biological science .\nstudies have indicated that proteins biological functions are determined by their dimensional folding structures . because the structure of a protein is strongly correlated with the sequence of amino acid residues , predicting the native conformation of a protein from its given sequence\nsince the problem is too difficult to be approached with fully realistic potentials , the theoretical community has introduced and examined several highly simplified models .\none of them is the hp model of dill et al . 1 . , 2 . , 3 . where each amino acid is treated as a point particle on a regular ( quadratic or cubic ) lattice , and only two types of amino acids\nalthough the hp model is extremely simple , it still captures the essence of the important components of the protein folding problem ( 4 ) .\nthe protein folding problem in the hp model has been shown to be np - complete , and hence unlikely to be solvable in polynomial time 5 .\n.. for relatively short chains , an exact enumeration of all the conformations is possible . in dealing with longer chains ,\nthe methods used to find low energy structures of the hp model include genetic algorithm ( ga ; ref . 8 . , 9 .\nthese algorithms can find optimal or near - optimal energy structures for most benchmark sequences , however , their computation time is rather long . in this paper ,\na branch and bound algorithm is proposed to find the native conformation for the two - dimensional ( 2d ) hp model .\nthe experimental results have shown that our algorithm is very efficient , which can find optimal or near - optimal conformations in a very short time for a number of sequences with lengths ranging from 20 to 100 monomers .\nthe monomers are numbered consecutively from 1 to n along the chain , which is folded on the square lattice , and each monomer occupies one site with the center on the lattice point .\nnote that each monomer should be connected to its chain neighbors and is unable to occupy a site filled by other monomers .\nif monomer i is placed on the square lattice , then the coordinates of its location are denoted by ( xi , yi ) .\nthe hp model is based on the assumption that the hydrophobic interaction is one of the fundamental principles in the protein folding .\nan attractive hydrophobic interaction provides for the main driving force for the formation of a hydrophobic core that is screened from the aqueous environment by a shell of polar monomers .\ntherefore , the energy function of the hp model is defined as:(1)e=-i , j < i-1ij where i = 1 if the i monomer in the chain is hydrophobic , otherwise i = 0 . in other words ,\nthe energy of a conformation can be obtained by counting the number of adjacent pairs of hydrophobic monomers ( h h ) that are not consecutively numbered , and multiplying by 1 .\nthe goal of the protein folding problem is to find the conformation with the minimal energy .\nit can be seen that each monomer occupies one lattice site connected to its chain neighbors .\nthe energy of this conformation is 4 , which is the lowest energy state of the sequence .\nin our algorithm , a conformation is built by adding a new monomer at an allowed neighbor site of the last placed monomer on the square lattice . in order to obtain a self - avoiding conformation ,\nthe monomers are placed consecutively until all the n ( the length of the chain ) monomers are placed , that is , our algorithm is a growth algorithm .\nif k 1 ( 1 k n ) monomers have been placed on the square lattice , the k monomer may have three possible locations : turn 90 right , turn 90 left , or continue ahead .\nfigure 2 gives a partial conformation where four monomers have been placed on the square lattice .\nthe next monomer , namely monomer 5 , can be placed at any one of these unoccupied positions , resulting in three different partial conformations accordingly . in this way\nas shown in figure 3 , a search tree representation can be used to denote all possible folding conformations , with three descendants at most for each node .\neach node in the search tree corresponds to a partial conformation , and a line between two nodes represents a placement choice of a new monomer to the existing partial conformation .\nconsequently , leaf nodes at the end of the tree correspond to the complete conformation . from figure 3 , it is obvious that the conformational space grows exponentially when the length of the protein chain increases .\nas mentioned by unger and moult ( 12 ) , the number of possible ( self - avoiding ) conformations for an l - long sequence on a 2d square lattice is al , where 2.63 and 0.333 .\naccordingly , for a protein chain of not too short length , the search space is too huge to find the lowest energy conformation within a reasonable running time . to reduce the computational cost ,\na so - called branch and bound method is introduced in this paper . in this search method , only the promising nodes are kept for further branching and the remaining nodes are pruned off permanently . since a large part of the search tree is pruned off aggressively to obtain a solution , its running time is polynomial in the size of the problems . in our algorithm , we treat h monomers and p monomers differently . for a partial conformation where\nk1 monomers have been placed on the square lattice , if the k monomer is p , then all possible branches should be kept .\notherwise , if the k monomer is h , then the benefit of all possible branches of the k monomer will be evaluated and some branches may be pruned .\nthat is to say , the main part of our algorithm is centered on the evaluation and pruning of the h monomers .\nthis strategy maintains the diversity of the conformations and eliminates the hopeless partial conformation at the same time .\nthe details are as follows : we set two variables , uk and zk , as the thresholds to evaluate the benefit of all branches for monomer k. here , uk is defined as the lowest energy of the partial conformation with length k that has ever been generated so far , and zk is the arithmetic average energy of the partial conformation with length k so far . after pseudo - placing monomer k at a possible location , we calculate ek , which is defined as the energy of the current partial conformation with k monomers placed .\nit should be pointed out that the term pseudo - place means that it is just a test and the placing process can be reverted .\nthen we compare ek with thresholds uk and zk : if ek uk , it means that this partial conformation is very promising and this branch should be kept .\nif ek > zk , that means the benefit of the partial conformation is below the average , so this conformation is discarded with probability 1 otherwise , if zk ek > uk , the partial conformation is discarded with probability 2 .\nthe pseudo - code of this subroutine is presented in figure 4 , including the details of evaluation criterion and the pruning mechanism , which is the main part of our algorithm .\nthe above process is implemented in a recursive way until all the conformations are either pruned or hit length n. from the conformations hitting length n , we choose one with the lowest energy as the output of the algorithm .\nit should be mentioned that the search could be implemented by depth - first or breadth - first , where the two results are identical . in this paper ,\nour algorithm is implemented by depth - first . here , emin is the minimal energy of the complete conformations ever built .\nnote that the first two monomers of a chain can be placed on the square lattice randomly .\nthe initial values of the two thresholds uk and zk are both 0 . obviously ,\nif 1 = 0 and 2 = 0 , the search space will be the complete tree ( no node be pruned ) and it will take a prohibitively long time to search for the lowest energy conformation . if 1 = 1 and 2 = 1 , it takes a very little time to search the entire search space because the thresholds are so high that many promising nodes may be discarded . that is to say , the higher the value of the probabilities , the more difficult a branch is to be kept .\ntherefore , choosing the value of 1 and 2 is an essential factor affecting the speed and efficiency of this approach . in this paper\nthe probability 2 is chosen to be less than 1 because a partial conformation with energy below average is more promising than a high energy partial conformation . in this way , ek , the energy of the partial conformation , can be viewed as the energy expectation of the partial conformation after looking one step ahead and zk is expressed as the mean energy of the already generated partial conformations of length k. zk keeps a historical record , which is , to a large extent , conducive to the formulation of promising conformations .\nfor any partial conformation , it would have more opportunities to procreate if holding higher individual quality ( ek ) , which is in accordance with the law of natural selection .\nto test the performance of the branch and bound algorithm , we compared it with the mc , ga , and mixed search ( ms ; ref . 13 ) algorithms by using 10 benchmark sequences for evaluation ( table 1 ) .\ntable 2 presents the results obtained by the four methods on the 10 different sequences .\nas shown in the table , our branch and bound algorithm can find the optimal lowest energy conformations for six sequences .\nit is noteworthy that our algorithm can find one native state for the sequence of length 60 , whereas the other three methods failed .\nfor the two long sequences of length 85 and 100 , respectively , our algorithm can find near - optimal energy conformations .\nit should be pointed out that predicting the longest sequence of length 100 is a hard problem , whose native state can only be obtained by a few methods such as the perm algorithm 14 .\n, 15 . and the guided simulated annealing method ( 7 ) . we did not compare the speed with other methods directly because the machines were different .\nmoreover , the running time of the other three methods was presented in terms of number of steps while the exact cpu time was used in our test .\nall the computations in this study were carried on a 2.4 ghz pc with 512 m memory .\nthe cpu time for all sequences was less than 10 s except the sequence of length 64 , for which the cpu time was 39.46 s. it can be seen from unger and moult ( 12 ) that the number of steps of mc and ga methods increases badly with the increase of sequence lengths , therefore , it is imaginable that the computational speed of mc and ga methods in unger and moult ( 12 ) for practical applications is unacceptable .\nthe resulting folding conformations for sequences with 24 , 36 , 60 , 85 , and 100 monomers are given in figure 5 , respectively .\nfor sequences with 24 , 36 , and 60 monomers , the corresponding conformations are all of the lowest energy . for the other two sequences with longer lengths , the corresponding conformations are also of near - optimal energy .\nit can be seen that the conformation has a single compact hydrophobic core for all sequences , which is analogous to the real protein structure .\nthe branch and bound algorithm proposed in this paper is a novel and effective tool for the conformational search in the low - energy regions of the protein folding problem in the 2d hp model .\nthe experimental results on 10 benchmark sequences demonstrate that our algorithm outperforms other three methods in terms of speed and efficiency .\nour algorithm is similar to the population control scheme ( 15 ) where individuals would have more opportunities to procreate if holding higher individual quality , and the pruning mechanism reduces considerably the computational burden of search .\nwe should point out that , the coding of this algorithm is very simple and hence it can be easily implemented by practitioners .", "answer": "a branch and bound algorithm is proposed for the two - dimensional protein folding problem in the hp lattice model . in this algorithm , \n the benefit of each possible location of hydrophobic monomers is evaluated and only promising nodes are kept for further branching at each level . the proposed algorithm is compared with other well - known methods for 10 benchmark sequences with lengths ranging from 20 to 100 monomers . \n the results indicate that our method is a very efficient and promising tool for the protein folding problem .", "id": 370} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbilateral carotid artery occlusion accompanied with basilar tip aneurysm is extremely rare.15 ) it has been suggested that increased blood flow through the vertebrobasilar system , which is the major source of collateral circulation , intensifies the hemodynamic stress on the arterial walls and this may result in the formation of saccular aneurysms.13 ) direct clipping for these aneurysms is difficult and the morbidity is high due to the extensive collateral networks as well as the already compromised cerebral blood flow and high internal blood pressure.2)3)7)14 ) thanks to the development of endovascular techniques , the aneurysms that are difficult to reach by craniotomy can now be treated with excellent results.3)4)6 ) to the best of our knowledge , there have been only seven cases of bilateral carotid artery occlusion with concurrent basilar tip aneurysm not being related to moyamoya disease.5)7)8)11)12)17)18 ) among them , only three cases were treated with coil embolization.7)12)17 ) we report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery ( ica ) occlusions with abnormal vascular networks from the posterior circulation .\na 43-year old man with a sudden onset of headache , nausea and vomiting visited the emergency room at our institution .\nhis aunt suffered from moyamoya disease , but he had not undergone diagnostic work - up for familial cerebrovascular diseases because he had not experienced neurological deficits such as ischemic attacks , including dysarthria , dizziness and gait disturbances .\nmentally alert , the patient had meningismus , experiencing neck stiffness on admission . a brain computed tomography ( ct )\nscan demonstrated diffuse and thick subarachnoid hemorrhage ( sah ) in the bilateral sylvian fissures , the anterior interhemispheric fissure , the basal cistern and the posterior fossa , including the perimesencephalic region ( fig .\nsubsequent carotid angiography showed complete occlusion of both icas , the so called ' bottle neck appearance ' or ' beak shape , ' at the level of the carotid bulb without appreciable intracranial filling and there were small collaterals from both external carotid arteries through the middle meningeal arteries to the anterior cranial fossa ( fig .\nvertebral artery angiography demonstrated that both hemispheres were seen filling in an antegrade fashion from the upper basilar artery and both posterior cerebral arteries through an extensive network of collateral vessels to the ica bifurcations .\na 6 4 mm aneurysm was also observed at the basilar artery bifurcation ( fig .\nperfusion ct scans revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to acetazolamide ( fig .\n4 ) . the abdominal ct aortograms did not demonstrate any other extracranial pathological vascular findings , including renal artery stenosis and fibromuscular dysplasia ( figures not shown ) .\ntwo guglielmi electrically detachable platinum coils and two hydrosoft helical coils were successfully deployed into the aneurysm .\nwe tried to deploy a microplex coil at the lower neck portion of the aneurysm , but failed due to the wide neck of the aneurysm .\nthe balloon or stent - assisted technique was not used even though there was a relatively large orifice because of the risk of thromboembolism and obstruction of the parent arteries during the procedure .\neventually , only the dome and waist of the aneurysm were packed completely ( fig .\nafter embolization , we closely monitored the patient 's neurological condition in the intensive care unit .\nthe first follow - up angiograms 6 months after treatment did not show aneurysm recanalization .\natherosclerosis and aortic inflammation are known to be the most common causes of bilateral carotid artery occlusion without moyamoya disease.17 ) atherosclerosis can occur at the point of ica bifurcation , leading to chronic and progressive arterial stenosis , whereas aortic inflammation is likely to be involved with the aortic arch and its branches , resulting in bilateral carotid artery occlusion .\ngenerally , an occlusion at the beginning part of the ica is likely to be caused by atherosclerosis , while the occlusion of the bilateral common carotid artery is likely aortitis.17 ) according to the study by aburahma and copeland,1 ) all patients with atherosclerotic bilateral ica occlusion had a history of cerebral ischemic attack such as transient ischemic attack ( tia ) , amaurosis fugax , or stroke even though collateral circulation was present , and they all needed surgical interventions such as endarterectomy , carotid - subclavian bypass or medical treatments using warfarin or aspirin .\nby contrast , definite cases of moyamoya disease are diagnosed in patients with bilateral stenosis or occlusion that occurs at the terminal portion of the ica together with an abnormal vascular network at the base of the brain , as is shown by cerebral angiography .\nthus , moyamoya syndromes that have underlying diseases such as cerebrovascular disease with atherosclerosis , autoimmune disease , meningitis , brain neoplasm , down 's syndrome , neurofibromatosis , head trauma or irradiation to the head , as well as other conditions , should be excluded.9 ) meanwhile , our case showed complete occlusion at the bilateral proximal portion of the internal carotid arteries above the carotid bulbs with abnormal vascular networks from the posterior circulation without basal moyamoya vessels .\nthe patient did not have any underlying diseases such as cerebral infection , trauma and aortic inflammation that may lead to stenosis or occlusion of the ica .\nalthough he had no past history of tia , he had two risk factors for atherosclerosis which were hypertension and smoking .\nno abnormal findings that may imply fibromuscular dysplasia were seen on the vertebral and abdominal angiograms .\nthese findings are not characteristics of moyamoya disease or moyamoya syndrome , but suggest idiopathic or atherosclerotic bilateral carotid artery occlusion .\nthe basilar tip aneurysm associated with bilateral carotid artery occlusion or moyamoya disease is well known , life - threatening complication that causes sah . to the best of our knowledge ,\nthere have been only seven cases of bilateral carotid artery occlusion with concurrent basilar tip aneurysm without moyamoya disease in the literature.5)7)8)11)12)17)18 ) the causes of carotid artery occlusion included aortic inflammation in two cases and atherosclerosis in five cases.5)7)8)11)12)17)18 ) of them , 5 cases had sah.8)11)12)17)18 ) it has been suggested that increased blood flow through the vertebrobasilar system , which is the major source of collateral circulation in bilateral carotid artery occlusion , intensifies the hemodynamic stress on the arterial walls and this may result in the formation of saccular aneurysms.13 ) although the formation of anastomosis from the external carotid artery may alleviate the hemodynamic burden on the posterior circulation , the effect is limited and local blood pressure still rises which leads to the risk of basilar artery aneurysms.17 ) conservative management for these aneurysms can lead to dismal results,11)18 ) therefore quick , aggressive treatments should be considered .\nhowever , direct clipping is difficult and dangerous due to extensive collateral channels,2)14 ) stiffness of the carotid artery,10)16 ) and high internal blood pressure.7 ) moreover , the fact that the basilar artery is the sole source of blood for most of the brain precludes prolonged temporary clipping to aid in safe dissection around the aneurysm.13 ) thus , these aneurysms have been recently treated with endovascular procedures using soft platinum coils .\nthere have been several reports have showing excellent results of endovascular embolization for the basilar tip aneurysms in patients with moyamoya disease and bilateral ica occlusion.4)6)7)10)12)17 ) of course , if increased blood burden through the vertebrobasilar system is not alleviated , the aneurysm will probably regrow .\nthus , in our case , regular follow - up angiograms are essential and additional embolization with extra - intracranial revascularization may be needed even though there was no perfusion defect seen on the perfusion ct scans .\nproximal bilateral ica occlusion is rare but often shows similar clinical features with moyamoya disease such as abnormal collateral vascular networks from posterior circulation and accompanying saccular aneurysms .\ndifferential diagnosis between idiopathic and atherosclerotic occlusion may be needed for further cardiovascular work - up .\nthe basilar tip aneurysm associated with proximal bilateral ica occlusion is more rare and dangerous , but curable disease .\nendovascular embolization for such aneurysms is safe and useful even without the assistance of balloon or stent .", "answer": "we report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery ( ica ) occlusions with abnormal vascular networks from the posterior circulation . a 43-year old man with a familial history of moyamoya disease presented with subarachnoid hemorrhage . \n digital subtraction angiography demonstrated complete occlusion of the bilateral icas at the proximal portion and a ruptured aneurysm at the basilar artery bifurcation . \n each meningeal artery supplied the anterior cranial base , but most of both hemispheres were supplied with blood from the basilar artery and the posterior cerebral arteries through a large number of collateral vessels to the ica bifurcation as well as the anterior cerebral and middle cerebral arteries . \n the perfusion computed tomography ( ct ) scans with acetazolamide ( acz ) injection revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to acz . \n an abdominal ct aortogram showed no other extracranial vessel abnormalities . \n a ruptured basilar tip aneurysm was successfully treated with coil embolization without complications . \n endovascular embolization may be a good treatment option with excellent safety for a ruptured basilar tip aneurysm that accompanies proximal ica occlusion with vulnerable collateral flow .", "id": 371} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the early 1960s ross and barratt - boyes introduced the use of human allograft cardiac heart valves , or homografts , into clinical practice [ 1 , 2 ] . in 2012 the 50th anniversary of the first so - called ross operation was celebrated . \nthe ross operation encompasses implantation of a pulmonary autograft in the aortic position , while an allograft is transplanted in the pulmonary position . \never since , there has been a need to store available donor grafts , so that they can be prepared , stored in a tissue bank , and used for implantation , either in elective or in emergency patients . from the end of the sixties and into the eighties tissue banks were founded all over europe . in the same period studies about the techniques and successes of homograft implantation in larger series of patients\nwere published , followed in the nineties by studies which covered more than a decade . because , over time , they were the only successful biological heart valve prostheses beside the mechanical ones , the results were very satisfactory . \nthe advantages were clear : a low rate of thromboembolic events , thus avoiding a lifetime of anticoagulation therapy .\nin addition , their hemodynamic properties were superior to those of mechanical valves , especially those available in the early 1960s and 1970s . \nas time went by , it became clear that the availability and cardiectomy techniques to obtain cardiovascular tissues were a problem as suitable donors were recipients of heart transplants , organ donors whose hearts were not accepted , or donors who were autopsied and their relatives had agreed to their tissues being used . \nin the last 20 years , the european cardiovascular tissue banks have invested a great deal of finances and effort in improving the safety and quality of their tissue banking methods and facilities .\nissues such as donor selection , validation of testing methods , the improvement of sterility systems and clean rooms were addressed . \nregulations based on directives of the european union became law in all member states . \nthe foundation of european tissue banks initiated a survey to obtain an assessment and quantification of the situation in the field of cardiovascular tissue banks , after implementation of the european directives into national legislation .\nin 2011 , questionnaires were sent out to 30 cardiovascular tissue banks , 18 of which completed and returned them .\none cardiovascular tissue bank had started its activities in early 2011 ; hence no data could be reported as yet .\nthree additional questionnaires were received after the statistical analysis was closed , and these data are not included . \nranges and means were calculated and tabulated giving insight into the level of activities of these cardiovascular tissue banks .\npercentages of detected positive serology were assembled , and a break - down of microbiological contamination as the reason for discarding tissue should yield information on the reasons for tissues being discarded during the process . \nthe statistics in table 1 are based on the assumption that every heart received in the cardiovascular tissue banks provided two grafts .\nout of 18 tissue banks , 11 had registered the number of donor reports rather than the hearts actually received in the bank . in these 11 tissue banks , 67% of the donors reported resulted in the receipt of a heart in the bank .\ntable 1 shows that from the total of 1640 hearts received by 18 tissue banks in 2010 , only 46.9% provided suitable grafts ; hence the discard rate is 53.1% . \nthe cardiovascular tissue banks show a considerable difference in their activities : while in 2010 the highest number of grafts received was 262 , the smallest bank processed only 17 grafts . when it comes to issuing grafts , similar differences are observed . as shown in table 2 ,\nthe statistics in table 2 confirm that the demand for pulmonary grafts is about twice as high as the demand for aortic valves : 67% of all grafts issued were pulmonary valves . the data provided by the 18 cardiovascular banks show that , in 2010 , exporting of tissues to other countries was done by 7 banks , with the proportion varying from 1% to 72% of the annual number of processed grafts .\nthe average donor age ranges from 40 ( in 2007 ) to 42 in 2010 .\nfifty - seven percent of the hearts originated from organ donors of whom the heart could not be transplanted , 28% from non - organ donors ( those who become donors after an extended period of cardiac arrest , and are thus unsuitable as organ donors ) and 15% were retrieved from so called domino donors .\ndomino donors are people who undergo a heart transplantation , and whose native heart may still have valves that are transplantable as tissue grafts . the criteria for the time between cardiac arrest and cardiectomy , as observed by the tissue banks in this study , ranged from 2 to 48 hours .\nin reality , the average time until cardiectomy was between 8 hours in 2007 , and 11 hours in 2010 .\nafter receipt in the tissue bank , the valvular grafts are excised from the heart and decontaminated . also here , the criteria differed greatly between the banks and the time varied from 18 hours to 72 hours , while the average number of hours in practice was 24 . \ntable 4 shows the reasons for discarding donor tissue . in 2010 , 45.3% of the tissue grafts had to be discarded . in many cases\nthere was more than one reason for not accepting the heart , or its tissue grafts , for transplantation .\nheart valve discards in 2010 , average % of all cardiovascular banks . in 32.7% of the cases\nthe reason for discard was that there were contraindications for transplantation of the tissue in the donor s medical history . during processing 35.8% of the cardiovascular tissue\nwas found to be unsuitable because of its morphology . in 17.65% and 4.2% of the cases , respectively , microbiology or serology test results were a reason not to accept the grafts for transplantation . \ntechnical and unknown reasons were responsible for 7.3% and 7.8% , respectively , of the discards .\nsubstantial differences can be observed in the number of hours during which the tissue banks culture the tissue to detect and/or eliminate micro - organisms ; the range is 5 - 72 hrs .\nalso , the temperature under which incubation takes place shows a large variety : from 4o c to 37o c. the banks use 25 different antibiotics in many different concentrations . in table 6\na breakdown of other tissues provided by the banks in this study shows that pericardium , arteries and veins are processed alongside valvular allografts .\nthe level of activity in cardiovascular tissue banks is determined by the numbers of donors .\nthis study shows that the range of donor hearts received in 18 banks varied from 1640 in 2010 to 1700 in 2007 . as the number of hearts received represents only 67% of the number of donors referred , it may be worthwhile to analyze the reasons why the hearts of 33% of the reported donors were eventually not allocated to the tissue bank . by eliminating factors preventing the donation from materializing\non the other hand the statistics document that in 2010 45.3% were not suitable for transplantation and had to be discarded .\nbetter donor screening beforehand , and a more effective process from cardiectomy to excision and for decontamination in the bank are three factors which could decrease this high number of discards .\nthis study shows in statistics what cardiovascular tissue bankers have known for a long time , that the demand for pulmonary valves is about twice as high as the demand for aortic valves : 66% of all grafts are pulmonary valves . \nalthough this study does not extend to the use of grafts , the literature shows that for many centers the pulmonary valve is the allograft of choice in congenital as well as in acquired cardiac diseases .\nthe activity of the banks varies from processing less than 20 to 262 donor hearts in 2010 .\none has to wonder about the routine capabilities of personnel as well as about the optimal use of the investment and costs of maintenance of a class a laboratory .\nthe donor age ( table 3 ) has gradually increased from an average of 40 in 2007 to 42 years in 2010 .\nas the average age in the european population increases , the donor age increases accordingly .\nthe reason is twofold : some authorities forbid the use of non - organ donors;to set up a cardiectomy team on a 24/365 basis requires additional organizational constraints and investments which some banks wish to avoid .\nsome authorities forbid the use of non - organ donors ; to set up a cardiectomy team on a 24/365 basis requires additional organizational constraints and investments which some banks wish to avoid .\nthe dependency on the receipt of organ donor and domino donor hearts brings them into a vulnerable position .\nthe need for additional cardiovascular grafts could be compensated by an effort to set up a non - organ donor program . \nhowever , the differences in decontamination methods , use of antibiotics and their concentrations , as well as temperature should be a subject to cause concern in the cardiovascular tissue banks participating in this study . in 2010 , a conference of these tissue bankers and their microbiologists was organized by the foundation of european tissue banks .\nsubstructuring and validation methods were exchanged , and some arguments were proven to be right . at that conference , and from the questionnaire in this study , no adverse events were reported by any of the participating tissue banks . while most of the cardiovascular tissue banks in this study concentrate on the processing and distribution of the classic homograft heart valves , nine banks showed activities with respect to processing tissues such as arteries , veins and pericardium .\ncorrespondence with different tissue bank representatives revealed that the demand for arterial grafts is growing throughout europe . while veins are used in access surgery ( shunts ) , pericardium serves as patching material to bridge larger gaps of deficient tissue during cardiothoracic operations . \nthe numbers of these tissues issued over the period 2007 - 2010 also show a considerable increase .\nfor the first time since the start of the clinical use of human allogeneic heart valves , data from a number of european cardiovascular tissue banks could be accumulated . \nstatistics with respect to numbers , discard and use of cardiovascular tissue provide insight into the magnitude of their activities as well as into some of the parameters they use . \nfirst of all , looking at the number of tissue grafts issued for transplantation , one can conclude that the demand for tissues has not decreased during the period of 4 years encompassed in this study . apparently the demand\nthe results show that cardiovascular tissue bank activities have remained relatively stable over the years , though the number of donors has somewhat decreased ( 3.5% ) .\nwhile the demand for pulmonary grafts still increased from 810 to 981 ( 21.1% ) , only 505 aortic grafts were issued in 2010 .\nwhat happens with all the aortic grafts which are not issued is a logistical as well as an ethical question . in order to cope with the persistently high demand for pulmonary grafts and arteries ,\nthose cardiovascular tissue banks which do not retrieve hearts from non - organ donors should seriously consider initiating such a donor program . \nalthough not clinically proven , studies show that stem cell techniques may eventually contribute to the quality and availability of human heart valves , yet none of the cardiovascular tissue banks indicated that they are in any way involved in stem cell research . \nthe differences in accepted time lapses from death to cardiectomy , and from cardiectomy until excision of the valves and further processing find their origin in view - points with respect to quality and safety . a consensus between the tissue banks contributing to this study should be based on data with respect to the potential loss of tissue quality starting at cardiac arrest and measured over time . \nas there are very large methodological differences with respect to microbiology testing , incubation and decontamination of cardiovascular tissue between the 17 contributing tissue banks , there is a necessity to validate procedures and room for improvement .\nthis survey shows an increased demand for other tissues , which may be worth further exploration .\nafter all , where alternatives seem to fail or are absent , it is the task of tissue banks to satisfy the clinical demand for tissue grafts .", "answer": "introductionin the past 50 years , human cardiovascular tissue allografts , also called homografts , have been implanted into patients with different valvular diseases . \n the use of these allografts and the number of cardiovascular tissue banks and their respective techniques increased . \n we conducted a survey to establish the quantity of allografts processed , and issued by , european tissue banks . \n the survey also included the collection of other relevant statistics.methodsin 2011 , the foundation of european tissue banks collected data from 19 different cardiovascular tissue banks in 11 european countries.resultsfrom 2007 to 2010 the data show a decrease in the number of hearts received , from 1700 to 1640 in 18 tissue banks ; the average number of hearts received for cardiovascular tissue processing decreased from 113 to 91 . \n the number of heart valves issued for transplantation increased from 1272 in 2007 to 1486 in 2010 . \n the average rate of discard because of microbiological contamination was 20.7% , while 4.2% of the grafts were not used because of positive serology . \n half of the tissue banks issued arterial grafts , while 3 banks also issued veins and pericardium . \n an overview of decontamination methods shows considerable methodological differencesbetween 17 cardiovascular tissue banks.conclusionsfrom the experience in europe , it can be concluded that cardiovascular tissue banks have an established place in the domain of cardiovascular surgery . \n the statistics show fluctuating data concerning the demand for human cardiovascular allografts and methodological questions . \n there is room for growth and improvement with respect to validation of decontamination methods .", "id": 372} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noroantral fistula ( oaf ) is an abnormal communication between the oral cavity and the maxillary sinus .\nthe chances of occurrence of oroantral communication increases , if there is an underlying peripical infection or a preexisting sinus disease .\nthe chronic long standing nature of oaf may be due to fungal infection like mucormycosis .\nthe sinus pathology is a predisposing factor for chronic non - healing nature of oaf .\nmany times this aspect is overlooked and simply the diagnosis of non - specific maxillary sinusitis is given , which leads to improper treatment .\nthe case we present here is a 34-year - old female patient [ figure 1a ] who was complaining about non - healing opening in the upper left front region and exposure of root of one tooth .\nthe lesion started as a small swelling in the left maxillary anterior vestibular area in the region of canine eminence .\nafter few days , patient noticed the area where the swelling ruptured was not healing and instead , it was showing small aperture .\nthe aperture went on increasing to the present size of 0.5 cm 0.5 cm .\npatient revealed the history of trauma in maxillary left front teeth region during field work 2 years back .\n( a ) a 34-year - old female patient presenting with mild to moderate swelling in left maxillary sinus area ( arrow ) .\n( b ) intraoral examination revealed the oroantral communication ( arrow ) in maxillary left anterior labial vestibule at mucogingival junction in the area of canine .\n( c ) the dorsal surface of tongue was coated with white leathery coat with central rhomboidal shaped erythematous area ( arrow ) .\n( d ) the cytosmear revealed pas positive numerous long thin filaments of candidal organism ( arrow ) .\nbudding yeast cells were seen scattered along the with pseudohyphae ( pas , 200 ) extraoral examination revealed a mild swelling in the left maxillary sinus area [ figure 1a ] . on intraoral examination\n[ figure 1b ] oroantral communication was noticed in maxillary left anterior labial vestibule at mucogingival junction in the area of canine .\nthe opening was around 0.5 cm 0.5 cm in size exposing the apical third portion of root of canine .\nthe dorsal surface of the tongue was coated with white leathery coat with central rhomboidal shape erythematous area [ figure 1c ] .\nno caries was detected in all maxillary left anterior teeth . on pulp vitality test maxillary left lateral incisor and canine was found to be non - vital .\nthe clinical diagnosis of oaf secondary to chronic periapical abscess in relation to maxillary left canine was established .\nthe conventional approach was undertaken to close the fistula and access opening was created in maxillary left canine .\npatient was followed up for observation of healing at closure of oaf and also to continue with root canal treatment of maxillary left canine .\nafter 4 weeks of primary closure of oaf , still there were no signs of healing and instead the oaf was re - established as it was before commencing the treatment .\npatient also complained of dull gnawing pain in the maxillary sinus area and more heaviness in the same region .\nlooking at non - healing chronic nature of oaf , the incisional biopsy from the margin of oaf was planned to seek histological changes in the region of oaf .\nbased on histopathological diagnosis , reclosure of oaf was planned . for chronic maxillary sinusitis antibiotics and nasal wash\nthe patient was followed - up regularly to assess for healing at oaf and check for the status of chronic maxillary sinusitis .\npatient reported with non - healing of oaf and even chronic maxillary sinusitis did not respond to treatment . this time to avoid surgical trauma , a cytological smear was prepared by swabbing the unhealed oaf .\ncytosmear stained with periodic acid schiff stain , revealed a pale homogenous stroma , with abundant acute inflammatory cells .\nnumerous long thin filaments of candidal organism having budding yeast cells were seen scattered along with pseudohyphae [ figure 1d ] . based on the cytological features , the diagnosis of oaf with superadded candidiasis was given .\nafter about 5 - 6 weeks patient was completely all right and clinical healing was complete .\nthere were no sign of candida organism on repeated cytological examination at the site of closure .\npresent case is an example for clinicians where they can learn that , sinus disease secondary to oaf is not only of bacterial origin but it could be also of fungal origin . since there is no history of extraction of tooth , oaf would have arisen due to periapical pathology secondary to trauma .\nthe candida organisms from oral cavity might have colonized the oaf leading to sinus pathology .\ncandida organisms can be easily detected at tissue level as candida hyphae at superficial epithelial surface , but sometime these superficial hyphae are washed away from tissue during processing in various chemicals .\nthis might be the reason why candida organisms were not detected and diagnosed in biopsied tissue .\nmere presence of this fungus in oral cavity is not sufficient to produce the disease .\nthere must be actual penetration of fungus in to the tissue , although such invasion is superficial and occurs only when there is breach in the continuity of epithelium .\nin present case , oaf must have become reason for the colonization of candida organisms over the maxillary sinus lining .\nthe other predisposing factors for candidiasis can be prolonged intake of antibiotics , corticosteroids ; anemia , etc . since initially patient was diagnosed with non - specific maxillary sinusitis .\nso inadvertent use of antibiotics could also be responsible for occurrence of superadded infection of candidiasis with oaf .\naccording to katzenstein , sinus mycoses can be classified as \n non - invasive chronic mycoses ( fungus ball),allergic mycosis , chronic indolent invasive mycosis , andfulminating invasive mycoses . \n \nnon - invasive chronic mycoses ( fungus ball ) , chronic indolent invasive mycosis , and fulminating invasive mycoses .\ntypes 3 and 4 are found in the immunosuppressed where as in immunocompetent , types 1 and 2 are common , with a granulomatous inflammatory response and necrosis .\ncandida organism can grow as opportunistic pathogen especially in presence of human immunodeficiency virus ( hiv ) infection .\nsince there was no hiv associated periodontal disease in patient , the remote possibility of hiv as cause for candida growth and occurrence of oaf could be ruled out .\nfurthermore , the mucosa of the dorsum surface of the tongue ( filiform papillae ) may represent a site of residual colonization and reservoir of organisms .\nsince patient 's dorsal surface of tongue was showing white coat with central erythematous area [ figure 1c ] .\nthis would have been possible source for colonization of candida organisms in maxillary sinus through oaf .\nthe mycetes most often involved was aspergillus fumigatus ( 76.9% ) . even after extensive literature search , no report was found for sinus formation with candida .\nthis case is good learning lesson for clinicians and histopathologists for stepwise approach in diagnosing oaf associated with sinus disease .\nit is understood that sinus pathology should be primarily treated for the successful closure of oaf . for the proper treatment of sinus disease identification of causative agent ( pathogen )\ntherefore , sinus disease secondary to oroantral communication should be primarily screened for pathogen through simple cytological approach .", "answer": "oroantral fistula ( oaf ) and oral candidiasis are common to come across as separate individual lesions . \n however when candida organisms infect maxillary sinus through oaf then diagnosis should not be limited to clinical diagnosis only . \n in such situation role of cytological examination can prove to be fruitful . \n a female with chronic long standing oaf , not responding to conventional treatment approach is reported . \n on incisional biopsy , the case was diagnosed as chronic maxillary sinusitis with oaf . \n however patient did not respond to any treatment approach and later presented with a more progressive lesion involving maxillary sinus . \n a cytosmear stained with periodic acid schiff stain , revealed the presence of numerous candidal hyphae . \n finally , case was diagnosed as oaf with a superadded candidal infection . \n patient responded well to antifungal treatment followed by reclosure of oaf . \n we should not neglect a simple cytological examination which may prevent wrong diagnosis and wrong treatment .", "id": 373} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwest nile encephalitis is a mosquito - borne disease endemic to africa , asia , australia , and europe and the west nile virus is a single - stranded rna virus which belongs to the japanese encephalitis serogroup of flaviviruses ( 1 ) .\nit could be accompanied with various neurologic symptoms and signs including headache , mental confusion , optic neuritis , and muscle weakness ( 2 , 3 , 4 ) .\nafter the first two cases of west nile encephalitis were diagnosed in 1999 in new york ( 5 ) , many neurological abnormalities were noted in patients of west nile encephalitis , and the flaccid muscle weakness is a distinctive feature of this disease ( 2 , 3 , 6 ) . until now\n, west nile encephalitis was never diagnosed in korea , and it is the first report of west nile encephalitis in korea .\na 58-yr - old man was admitted with headache for 2 months in june 2012 .\nthe patient had been on a business trip in guinea , west africa since 7 months ago .\nhe denied other symptoms such as nausea , vomiting , neck stiffness , and dizziness .\nthe headache and cognitive impairment had been worsening and accompanied general weakness and weight loss 10 kg for 2 months .\nhe had no hypertension , cardiac diseases , chronic renal disease , and liver disease .\nhe had a 20 pack - year history of smoking and no recent alcohol intake .\nthe patient denied using any medications except for antimalarial drug ( sulfadoxine 500 mg , pyrimethamine 25 mg , artemether 80mg / ml ) and analgesics in africa . at admission to our hospital , he was afebrile ( 36.4 ) and his vital signs were blood pressure 121/78 mmhg , heart rate 97/min , and respiratory rate 20/min with normal findings of physical examinations .\nfindings on initial neurologic examinations were normal except minimental state examination ( mmse ) with score 20 .\nadmission complete blood count revealed hemoglobin of 12.7 g / dl , leukocyte count of 16.2 10/l with 79% neutrophils , and a platelet count of 388 10/l . the patient 's calcium level , chemistries , and liver function tests were normal and crp was slightly increased .\nanalysis of cerebrospinal fluid ( csf ) demonstrated 0 rbc/l , 214 wbcs/l ( with 80% lymphocytes and 12% neutrophils ) , a protein level of 161.9 mg / dl , a glucose level of 93 mg / dl and ada level of 4.8 .\na brain magnetic resonance imaging ( mri ) revealed multifocal patchy t2 high signal lesions in both temporal lobes , basal ganglia , internal capsule posterior limb , and corona radiata , which suggested encephalitis .\nelectroencephalogram showed frequent semirrhythmic medium amplitude delta slowing on both hemispheres , with frontal dominancy . on hospital day 1 , his body temperature was 38.0 and malaria test was negative .\nfollow up csf tapping was done on hospital day 3 and 6 rbc/l , 340 wbcs/l ( with 67% neutrophils and 28% lymphocytes ) , a protein level of 164.6 mg / dl , a glucose level of 70 mg / dl and ada level of 6.0 .\nthe patient complained of both leg weakness and the motor strength of bilateral lower extremity was 4+/4 + .\nhe also complained of both leg pain and paresthesia , deep tendon reflex on both lower extremities were areflexia .\nthere was no remarkable finding on nerve conduction study ( ncs ) and needle electromyogram ( emg ) , but arachnoiditis and myelitis were observed on lumbar spine mri ( fig .\npolymerase chain reactions ( pcr ) for hsv , vzv , ebv , cmv , enterovirus , tuberculosis , and mycoplasma pneumonia were negative in csf .\nserological test for brucellosis , lyme disease , leptospirosis , hantann virus and tsutsugamuchi disease were negative at admission\nan additional serological study for specific antibody for west nile virus was done , the total antibody titer of west nile virus was 1:337 , and follow up titer after 2 weeks was 1:1,632 in serum by plaque reduction neutralization test .\ntreatment with interferon- 3mu was started and maintained for 2 weeks . follow up csf tapping was done after one month later and 9 rbc/l , 9 wbcs/l ( with 16% neutrophils and 67% lymphocytes ) , a protein level of 99.9 mg / dl and a glucose level of 66 mg / dl .\nencephalitis with severe muscle weakness is a common symptom and may provide a diagnostic clue . to confirm a diagnosis , it needs identification of west nile virus in serum or csf .\nigm antibody is usually detectable only during a few days of illness ( 7 ) .\nanother method is the identification of a change by a factor of four or more in the antibody titer or virus - neutralization tests ( 7 ) , the case was positive for the virus - neutralization tests .\nserological test and pcr for other infectious agents were all negative and autoimmune encephalitis such as nmda receptor encephalitis was excluded by clinical symptoms ( 8) .\nmany studies indicated that the weakness was probably caused by infection and inflammation in the anterior horn cells of the spinal cord and brainstem like poliomyelitis ( 6 , 9 , 10 ) .\nelectrophysiologic studies showed reduced compound muscle action potentials , and normal sensory nerve action potentials , which is distinguished from guillain - barre syndrome ( 3 , 6 , 9 , 10 ) .\na few autopsy studies demonstrated that the inflammatory changes with severe leukocytic inflammation of the anterior horns with striking loss of motor neurons ( 4 , 11 ) . but this case did not present any abnormalities in the electrophysiologic study .\nhe complained about severe sensory symptoms with leg pain and arachnoiditis was observed in lumbar mri .\nonly a few reports noted a caudal equine enhancement ( 4 ) and weakness due to acute radiculitis ( 12 ) .\nit 's hard to say that his weakness was caused by only radiculopathy , because paralysis of the west nile encephalitis generally results from anterior horn cell damage .\nbut in this case , radiculopathy also contributes the motor weakness of the west nile encephalitis . at present\nthere is no established treatment for west nile encephalitis and basic treatment is a supportive care .\nbut because it 's a fatal disease , sometimes it was treated with plasmapheresis or administration of iv immunoglobulin ( 5 ) .\ninterferon- has been reported to inhibit west nile virus replication , and some successful cases were reported using of interferon- to treat west nile encephalitis ( 13 ) .\nkorea is not an endemic area of west nile virus , but an increasing overseas trip poses a risk of the influx of overseas diseases and may contribute to the global spread of infectious diseases .", "answer": "west nile encephalitis was first identified in 1937 , but until now , it was never diagnosed in korea . \n a 58-yr - old korean man was admitted with headache and cognitive dysfunction . \n the patient had been on a business trip in guinea . \n cerebrospinal fluid ( csf ) showed pleocytosis . \n the patient complained of both leg weakness , and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging ( mri ) . \n a specific neutralizing antibody for west nile virus was positive in serum . \n after a treatment with interferon- 3mu , follow up csf findings recovered completely after 3 months later . \n the first case of west nile encephalitis in korea was imported from guinea , and was cured successfully.graphical abstract", "id": 374} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nMINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics\n\nPaper sections:\nBackground\nMetabolomics, the study of the population of small molecules in a cell, has drawn intense interest in fields from medicine to synthetic biology because it can provide a fine-grain representation of cellular state and activity [1\u20134]. Of particular interest is untargeted metabolomics, which seeks to measure as much of the metabolome as possible by limiting methodological detection bias. The dominant analysis technique for untargeted metabolomics is chromatography coupled with mass spectrometry (MS) but this method is hindered by a large number of unknown peaks [5] and the limited number of reference spectra available to identify the peaks [6]. A number of tools have been developed to propose structural matches for unannotated peaks [7\u201311] but in practice these tools either return too many candidates when drawing from large chemical databases such as PubChem [12] or miss compounds not yet present in curated biochemical database [13, 14].This has the effect of locking untargeted metabolomics in a unfortunate paradox: compounds that are not present in biochemical databases are not identified and in the absence of experimental identification, new compounds cannot be added to databases [15].
There is a growing consensus that many enzymes mediate undocumented side-reactions (known as promiscuous activities) as a result of exposure to diverse cellular metabolites [16, 17]. These activities may explain unannotated peaks in metabolomics datasets [18, 19] but are difficult to detect as they may be overshadowed by a known function [20] or be dependent on intracellular conditions [21]. Predicting novel chemical reactions based on broad enzyme specificity has been utilized by a number of tools for the prediction of new biochemical pathways [22\u201324]. Recently, this technique has also been used to expand structure databases for metabolomics by the MyCompoundID tool [25] the In Vivo/In Silico Metabolites Database (IIMDB) [15], LipidHome [26] and others [27, 28].
Here we present Metabolic In silico Network Expansions (MINEs) that utilize the Biochemical Network Integrated Network Explorer (BNICE) [29, 30] to expand on general biochemical databases as well as organism-specific databases for Escherichia coli and yeast. The focus on endogenously present and organism-specific metabolites has been cited as critical to improving the confidence of compound matches [5] and thus we complement existing resources that focus on human metabolism. In principle, these predictions could also be made using Reaction Difference Matching (RDM) [23], machine learning methods [31, 32], or other rule-based methods such as ChemAxon's Metabolizer. Each of these approaches has their benefits; the output really depends on the quality and coverage of the reaction rules used in the analysis. We selected BNICE because we have a set of BNICE reaction rules that have been demonstrated to reproduce a large fraction of known biochemical reactions [24], as well as to predict enzyme reactions that were subsequently verified experimentally [33]. Importantly, we also have the right to re-distribute BNICE output. No license is required for academic users to access the website or APIs and all BNICE predicted compounds are available for download in SDF format from the website.
\n\n\nMINE database construction and access methods. The process of constructing a MINE database from the curated source databases is depicted on the left. The methods for accessing the database are shown on the right.
\n\nConstruction and content\nCompound information was obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) (Release 68.0) [36], the Yeast Metabolome Database (YMDB) (Version 1.0) [37] and EcoCyc (Version 17.0) [38]. Generalized (containing R groups), inorganic compounds, and disconnected fragments were removed using the Pybel toolkit [39]. Generalized structures are of very limited utility, as they cannot be assigned an accurate mass or represented in a canonical form. Where possible, we encourage developers to avoid ambiguity by enumerating all possible structures in their databases. Additionally, biochemical databases often contain numerous duplicate compounds [40] and these were identified by Standard InChIKey [41] comparison and removed for computational efficiency.
\n\n\nGeneralizing a BNICE reaction rule from known biochemical reactions. The common motif of the hydrolysis of the 1,3-diketone is shaded for emphasis.
\n\nConstruction and content\nBNICE products may take a variety of tautomeric forms depending on the source structure and the nature of the operator applied. Therefore, products were processed with ChemAxon's Standardizer & Structure Checker (JChem 6.0.4, 2013) to ensure canonical valences and placement of charge. Natural Product Likeness scores [42] and estimated logP values were calculated with a standalone Java ARchive (JAR) package and ChemAxon's Calculator Plugins (JChem 6.0.4, 2013) respectively. Estimated Kov\u00e1ts Retention Indices were calculated using the NIST RI algorithm [43].
Compounds were matched to PubChem [44] and KEGG COMPOUND databases with the connectivity block of InChIKeys for annotation. Generated compounds are assigned identifiers based on hash of the canonical SMILES [45] for internal use and a numeric MINE ID for human readability. Finally, the exact mass and chemical fingerprints of structures were calculated with Pybel.
Compound and reaction data is stored as collections in a Mongo Database (v2.6.2). A compound entry contains the chemical formula, exact mass, InChIKey canonical SMILES [45], FP2 and FP4 fingerprints and lists of reactions in which the compound is predicted to participate as a reactant or product. A compound may also be annotated with additional information such as common names or database links if it matches a KEGG or PubChem entry. Reactions are uniquely identified by an 'R' followed by the SHA1 hash of the sorted chemical reaction. Reactions entries contain arrays of reactants and products as tuples of the stoichiometric coefficient and the compound ID as well as a list of the operators that predicted the reaction.
\n\n\nComparison of MINEs generated from various source databases and other databases containing computationally predicted metabolites
Histogram of Natural Product Likeness. This plot shows the distribution of Natural Product Likeness Scores for the KEGG Database (mean score 0.77), the KEGG MINE (mean score 0.98) and a random sample of 500,000 PubChem compounds (mean score \u22120.52). A more positive score indicates more natural atomic features.
Screenshot of Metabolomics search results. This screenshot displays features of the metabolomics results including filtering by attributes and highlighting (blue) of compound present in a specified KEGG genome reconstruction.
Annotation of MassBank data
\n\nUse case: annotation of accurate mass datasets\nFinally, to demonstrate the practical utility of MINE databases, we utilized the EcoCyc MINE to annotate untargeted metabolomics data from an E. coli knockout study analyzed by LC\u2013MS. The protocols for sample extraction, data acquisition and post processing are available in the supplementary information. 493 distinct exact MS features were extracted, 30 of which were identified following a traditional annotation workflow using NIST MSPepsearch (see Additional file 2); in contrast, the EcoCyc MINE database proposed candidates for 132 of the accurate masses when searching with 5 mDa precision and with [M+]+, [M+H]+, [M+Na]+ adducts. The resulting MINE candidates were consistent with 93% of the NIST MSPepsearch results.
\n\n\nPositive MS spectrum (a), positive MS/MS spectrum (b) and negative MS/MS spectrum (c). The positive MS spectrum provides the mass of the precursor ion [M+H]+\u00a0=\u00a0690.5099\u00a0Da and its isotopic abundance pattern. The prominent ion in the positive MS/MS spectrum corresponds to the neutral loss of the phosphoethanolamine head group. The negative MS/MS spectrum shows the molecular ion [M\u2212H]\u2212 as well as a pair of ions corresponding to the (16:0) and (16:1) side chains.
\n\nFurther development\nIn addition to the existing web tools, the underlying MINE databases are accessible through free, developer-friendly APIs. Clients are available for integration into Python, Perl and JavaScript frameworks at https://github.com/JamesJeffryes/MINE-API. This API allows the databases to be integrated into existing candidate ranking algorithms and pipelines. Future versions of these databases will incorporate transformation rules for spontaneous chemical reactions of metabolites, and improved filtering and prioritization of candidate structures.
In addition to expanding the scope for the metabolome, the MINE framework also offers a pipeline for illuminating the synthesis and degradation of poorly annotated secondary metabolites. While applied very broadly to nearly all of metabolism in this study, BNICE expansions may be focused on a region of interest in the metabolic network by adjusting the starting compounds and permissible transformations in a manner similar to that recently demonstrated by Ridder et al. [27]. These targeted MINEs will integrate the generation of plausible pathways by BNICE with the tools to detect the presence of predicted pathway intermediates with accurate mass spectrometry thereby accelerating the process of proposing and evaluating hypothetical enzymatic synthesis routes for a number of compounds of interest.
\n\nConclusions\nHere we have presented Metabolic In silico Network Expansions (MINEs) that utilizes generalized biochemical transformations to propose structures for use in untargeted metabolomics. The resulting compounds are rarely found in PubChem but are structurally similar to natural products. We have demonstrated the utility of these databases for proposing correct metabolite structures that stymied a standard annotation workflow. MINE data are accessible without licensing restrictions for non-commercial users through a user-friendly web interface and API for developers in several common scripting languages.
\n\nAvailability and requirements\nMINE databases are freely accessible at: http://minedatabase.mcs.anl.gov and API clients are available at https://github.com/JamesJeffryes/MINE-API. There are no restrictions for Academic Use. Commercial users must obtain a license from Pathway Solutions Inc. (www.pathway.jp) and explicit permission from the authors.
\n\n\nTransformations of High and low Natural Product Likeness compounds.
Sample extraction, LC\u2013MS data collection and processing protocols and repository access.
Metabolic In Silico Network Expansions
natural products
liquid chromatography\u2013mass spectrometry
Biochemical Network Integrated Computational Explorer
Kyoto Encyclopedia of Genes and Genomes
International Union of Pure and Applied Chemistry
IUPAC International Chemical Identifier
Application Programing Interface
", "answer": "BackgroundIn spite of its great promise, metabolomics has proven difficult to execute in an untargeted and generalizable manner. Liquid chromatography\u2013mass spectrometry (LC\u2013MS) has made it possible to gather data on thousands of cellular metabolites. However, matching metabolites to their spectral features continues to be a bottleneck, meaning that much of the collected information remains uninterpreted and that new metabolites are seldom discovered in untargeted studies. These challenges require new approaches that consider compounds beyond those available in curated biochemistry databases.DescriptionHere we present Metabolic In silico Network Expansions (MINEs), an extension of known metabolite databases to include molecules that have not been observed, but are likely to occur based on known metabolites and common biochemical reactions. We utilize an algorithm called the Biochemical Network Integrated Computational Explorer (BNICE) and expert-curated reaction rules based on the Enzyme Commission classification system to propose the novel chemical structures and reactions that comprise MINE databases. Starting from the Kyoto Encyclopedia of Genes and Genomes (KEGG) COMPOUND database, the MINE contains over 571,000 compounds, of which 93% are not present in the PubChem database. However, these MINE compounds have on average higher structural similarity to natural products than compounds from KEGG or PubChem. MINE databases were able to propose annotations for 98.6% of a set of 667 MassBank spectra, 14% more than KEGG alone and equivalent to PubChem while returning far fewer candidates per spectra than PubChem (46 vs. 1715 median candidates). Application of MINEs to LC\u2013MS accurate mass data enabled the identity of an unknown peak to be confidently predicted.ConclusionsMINE databases are freely accessible for non-commercial use via user-friendly web-tools at http://minedatabase.mcs.anl.gov and developer-friendly APIs. MINEs improve metabolomics peak identification as compared to general chemical databases whose results include irrelevant synthetic compounds. Furthermore, MINEs complement and expand on previous in silico generated compound databases that focus on human metabolism. We are actively developing the database; future versions of this resource will incorporate transformation rules for spontaneous chemical reactions and more advanced filtering and prioritization of candidate structures.Graphical abstractMINE database construction and access methods. The process of constructing a MINE database from the curated source databases is depicted on the left. The methods for accessing the database are shown on the right.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-015-0087-1) contains supplementary material, which is available to authorized users.", "id": 375} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen you hear hoofbeats , think of horses not zebras , the art of medicine is based on soundness : the higher the pretest probability , the sounder the diagnosis .\nthe problem with this medical aphorism is that it actively encourages the clinician to turn a deaf ear ( and a blind eye ) to the possibility of lesser known and , therefore , more easily overlooked disease states that mimic or \nthis report presents a case in point : a 47-year - old woman with triple - negative breast cancer on a clinical trial called primetime ( nct02518958 ) who received the anti - pd-1 inhibitor nivolumab and the experimental anticancer agent rrx-001 for 18 weeks ; initially treated for pneumonitis , an \nexpected autoimmune complication of nivolumab , based on the development of dyspnea and ct abnormalities . the overall clinical picture , nevertheless , was atypical , which prompted the investigating team to aggressively pursue alternate possibilities , ultimately leading to the correct diagnosis : pulmonary tumor thrombotic microangiopathy or pttm .\nthis example highlights the importance of exercising due diligence and not automatically jumping to conclusions with regard to the diagnosis of immune - related adverse events ( iraes ) such as pneumonitis during treatment with pd-1 or ctla-4 inhibitors .\nanalogous to another pulmonary medical aphorism , all that wheezes is not asthma , the differential diagnosis for breathlessness in the context of immune checkpoint inhibition is broader than only pneumonitis and should involve a systematic investigation for other etiologies , including the rare and rapidly progressive disorder pttm . a case history and review of the literature\nare presented for pttm , which we propose to define as a paraneoplastic syndrome ( pns ) . in addition , a potential treatment option based on its pathophysiology is discussed .\nthe goal of cytotoxic t - lymphocyte antigen-4 ( ctla-4 ) and programmed death-1 ( pd-1 ) pathway blockade , including nivolumab approved for the treatment of melanoma , squamous - cell lung cancer and renal cell carcinoma , is to overcome the t - cell suppression mediated by these inhibitory receptors ( fig .\n1 ) ; a potential side effect of revving up the immune system to attack malignant tumors is the breaking of self - tolerance and the induction of iraes , which include rash , colitis , hepatotoxicities , endocrinopathies , and interstitial pneumonitis . as the most serious irae ,\nreportedly responsible for 5 total fatalities across the spectrum of nivolumab - treated patients , the incidence of pneumonitis increased from 3.4% on a melanoma trial to 6% on a nsclc clinical trial , according to a recent bristol myers squibb press release ; this increase in incidence should raise the suspicion that increased awareness of and , consequently , narrowed focus on pneumonitis by oncologists has resulted in erroneous overdiagnosis .\nthe clinical manifestations of pneumonitis are protean and include fever , chills , malaise , cough , chest tightness , hypoxia , and dyspnea , while the nonspecific radiological characteristics of ground glass opacities ( i.e. , lung opacities that do not obscure the associated vessels ) , consolidations ( i.e. , lung opacities that do obscure the associated vessels ) , and effusions also overlap with multiple other disease entities including acute respiratory distress syndrome , pneumonia , pulmonary embolism ( pe ) , congestive heart failure , and the subject of this case report , pttm .\npttm is a rare and possibly underdiagnosed extrapulmonary sequella of metastatic cancer , specifically adenocarcinomas , formally described in 1990 by von herbay et al . \nthat presents as acute cor pulmonale , a maladaptive response to pulmonary hypertension , resulting in dyspnea and hypoxemia as well as ground - glass opacity ( or diffuse consolidation ) and pulmonary edema on ct [ 12 , 13 ] .\nthe available literature on pttm is sparse , existing mostly as case reports or small case series from japan , with a lack of higher - order treatment studies .\nadenocarcinomas , and gastric cancer in particular , have been linked with pttm in these japanese case reports , which is not surprising , given the high incidence rate of gastric cancer in japan .\nthe etiologic mechanism of pttm is related to the intravasation of circulating tumor cells in the pulmonary vasculature ; these circulating tumor cells release a plethora of vascular remodeling factors including vascular endothelial growth factor ( vegf ) , fibroblast growth factor , osteopontin , and platelet derived growth factor ( pdgf ) associated with abnormal endothelial proliferation , the local activation of the coagulation cascade , and the development of pulmonary hypertension from resultant stenosis of the pulmonary capillaries and arterioles ( fig .\nwhich is only rarely diagnosed antemortem , due to a nearly uniform fatality rate , ( almost all reported patients have died within 2 weeks of dyspnea onset ) , may be suspected in cancer patients ruled out for pe who develop acute or subacute right - sided heart failure , pulmonary hypertension , and abnormal coagulation parameters .\nour nivolumab - treated patient with metastatic triple - negative breast cancer who is the subject of this case report recapitulated these clinical and laboratory abnormalities almost to a t , including , unfortunately , the time interval between onset of first symptoms and death .\nwhile the term textbook example is not applicable in the context of pttm , since no textbooks on it have been written ( only case reports ) , this patient 's clinical course and trajectory were indeed \ntextbook for pttm , even though a default diagnosis of nivolumab - induced pneumonitis was initially made .\nhowever , in light of the atypical presentation , discussed below , and findings that did not quite \nadd up , the team , suspecting that pneumonitis was a red herring , decided to trust their intuition , and pursued a further work - up , which ultimately led to the diagnosis of pttm .\na 47-year - old female with rapidly progressive refractory triple - negative metastatic breast cancer , metastatic to the lungs , was treated at walter reed on a clinical trial called primetime ( nct02518958 ) where she received the anti - pd-1 inhibitor nivolumab , 3 mg / kg , every other week in combination with weekly rrx-001 , an experimental epi - immunologic agent . during her week 18 infusion on december 3 , 2015 ,\nshe developed fever ( 101f , 38.3c ) , headache , palpitations , and diaphoresis ; the presence of fever prompted a sepsis work - up consisting of complete blood count , routine blood culture , urinalysis , and chest x - ray in the hospital to determine the source of the fever and rule out an infection .\nher labs were otherwise significant only for anemia ( hemoglobin 9.4 g / dl and hematocrit 30.6% ) and a normal leukocyte count ( 5.8 10/l ) with a high percentage of segmented neutrophils on the differential ( normal 4373% ) and no bandemia . as part of the work - up for sinus tachycardia ,\nthyroid function tests were performed but thyroid - stimulating hormone ( tsh ) and free t4 were within normal limits .\nher symptoms progressed to dyspnea and hypoxia the next day ( on december 4 , 2015 ) after administration of isotonic normal saline to restore volume .\nchest ct , which had been clear on admission , revealed interlobular septal thickening , diffuse ground - glass attenuation , and bilateral effusions ( fig .\n3 ) . a shortened list of differential diagnoses included atypical viral or bacterial pneumonia , cardiogenic pulmonary edema ( since the patient had received doxorubicin in the past ) , and treatment - induced pneumonitis . on that basis ,\nfluids were withheld , the patient was discontinued from the trial and combination treatment with broad - spectrum empiric antibiotics ( vancomycin , zosyn and levaquin ) and 1 mg / kg prednisone was started .\nhowever , the antibiotics and corticosteroids were withdrawn a week later due to worsening dyspnea and hypoxia .\na ventilation - perfusion scan was performed on december 14 , 2015 and read as low probability for pe ( no perfusion defects ) . to identify the cause of the edema ,\na transthoracic echocardiography was ordered , which revealed a normal left ventricular ejection fraction with right ventricular dilatation and severely reduced right ventricular function secondary to pulmonary hypertension ( a pressure > 50 mm hg is generally accepted as severe and her estimated right ventricular systolic pressure exceeded 65 mm hg ) .\nprobnp was also drawn ; it was elevated at 3,226.0 pg / ml , indicative of heart failure ( 5125 nl range ) .\nthe presence of acute cor pulmonale pointed away from pneumonitis and strongly suggested three rare possibilities : ( 1 ) occlusion of the pulmonary vessels from microscopic tumor emboli ( also known as pulmonary tumor embolism ) , leading to pulmonary arterial hypertension ( pah ) ; ( 2 ) pttm , a related but even rarer pulmonary vasculopathy , associated with adenocarcinomas of the stomach , pancreas , breast , lung , and liver , in which minute tumor emboli in the peripheral pulmonary arteries damage the vascular endothelium , leading to accelerated coagulation and pah , and ( 3 ) pulmonary venous occlusive disease , the venous form of pah [ 19 , 20 ] , due to fibrous occlusion of the post - capillary vessels , which may or may not be associated with an autoimmune process ( the association is only anecdotal ) . the pulmonary hypertension was managed with diuretics ( furosemide 40 mg i.v . ) , bosentan 62.5 mg , and oxygen ( 2 liters by nasal cannula ) as well as intravenous epoprostenol , norepinephrine , and dobutamine ; however , no improvement was observed .\nsince a lung biopsy carried too much risk , the patient was catheterized ; pulmonary artery catheter - derived blood samples were negative for the presence of tumor emboli .\nblood was also drawn for the measurement of coagulation parameters , since pttm is associated with coagulopathy .\nthe results were as follows : elevated d - dimer ( or serum fibrin degradation products ) of 1.04 g / ml ( normal < 0.5 g / ml ) and a prolonged prothrombin time of 16.5 s ( normal 1114 s ) .\nplatelets were never outside of the normal range . the partial thromboplastin time and thrombin time\nwere both prolonged at 67.2 s ( normal 2535 s ) and 48 s ( normal 1420 s ) , respectively , due to treatment with a heparin gtt for potential venous clots . in the setting of adenocarcinoma , pulmonary hypertension , and a negative ct and ventilation - perfusion scan for pe ,\npttm is distinct from simple embolic obstruction because it is characterized by ( 1 ) the systemic activation of coagulation with the generation of intravascular fibrin and the consumption of procoagulants , leading to a disseminated intravascular coagulation - like picture , present in this case and ( 2 ) remodeling of the pulmonary vasculature due to expression of vegf and pdgf from embolic tumor cells ( see fig .\n2 ) . based on the proposed involvement of vegf and pdgf in the pathogenesis of pttm , the primary investigator planned to treat the patient with sunitinib , which dually inhibits vegf and pdgf pathways\nthe observations in this case study strongly suggest that pd-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default , requiring a thorough work - up to rule out conditions that may mimic it , including pe , atypical pneumonia , pulmonary venous occlusive disease , congestive heart failure , and pttm . in the case of this acutely dyspneic patient , who initially received a\n pneumonitis by default diagnosis , pttm was only identified when her shortness of breath deteriorated despite treatment with high dose steroids , alerting the principal investigator to the possibility of heart failure , which led to further investigation .\nthe treating oncologist must be alert to the development or presence of pns , defined as a pathology caused by tumor cells , which systematically produce a large amount of hormones , growth factors , cytokines and a variety of specific symptoms .\nthese include : cushing syndrome , carcinoid syndrome , dermatomyositis - polymyositis , myasthenia gravis and syndrome of inappropriate antidiuretic hormone . to this list\n, we would add pttm , since its pathogenesis is related to the local release of mitogenic factors associated with vascular remodeling and coagulopathy . as a heretofore unrecognized pns\n, pttm requires background knowledge and a high index of clinical suspicion . in the absence of a biopsy ,\neven though the case under discussion was refractory to standard therapies and the patient died before sunitinib , the multitargeted tyrosine kinase selective for vegf and pdgf receptors , could be started , it is reasonable to assume that early diagnosis and treatment would have resulted in a better outcome .\nthe patient described in this case report has given his informed consent as part of the primetime clinical study ( nct02518958 ) .\nthis study protocol has been approved by the walter reed national military medical center institutional review board .", "answer": "a case report of a 47-year - old woman with triple - negative breast cancer on a clinical trial called primetime ( nct02518958 ) who received the anti - pd-1 inhibitor nivolumab and the experimental anticancer agent rrx-001 is presented . although initially diagnosed and treated for anti - pd-1-induced pneumonitis , clinical and radiological abnormalities triggered further investigation , leading to the diagnosis of pulmonary tumor thrombotic microangiopathy ( pttm ) . \n this example highlights the importance of exercising due diligence in determining immune - related adverse events and suggests that pd-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default . \n a case history and review of the literature are presented for pttm , which we propose to define as a paraneoplastic syndrome .", "id": 376} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmyofascial pain syndrome ( mps ) can be caused by frequent muscle or fascial stiffness as a \n result of prolonged tension and muscle fatigue due to repetitive stress of muscles or \n overuse of particular muscles1 , 2 .\nmps activates trigger points in 54% of women and 45% of men , and is regarded as \n the most common cause of pain in the musculoskeletal system3 . in particular , the upper trapezius requires head movement according \n to the direction of view , but it can be vulnerable to damage when the hands and arms are \n used repetitively in work that requires precise control4,5,6 . once myofascial trigger points are activated , changes in the \n structural characteristics and contraction function of the muscle will occur .\nthe most \n distinctive changes are taut bands , tender nodules , referred pain , local twitch response , \n muscle weakness , and restricted range of motion3 .\nto evaluate the contraction function of skeletal muscle , various methods can be used . among \n them ,\nsurface electromyography ( emg ) analyzes functional changes in muscle by measuring \n quantitative changes in motor unit action potential that is activated by muscle \n contraction7 , 8 .\nsurface emg is widely used in kinetic analysis to diagnose normal \n or abnormal function in muscles and nerves according to amplitude and frequency9 .\nit has several advantages , as it is \n noninvasive and convenient , and can perform measurement even during dynamic motion10 , 11 .\nalthough a number of clinical reports on the pathologic mechanisms or clinical diagnosis \n and treatment of mps can be found , few studies have been conducted on the changes in \n contraction function in myofascial trigger point areas or on the electrophysiological \n characteristics and neuromuscular physiological information .\nthis study aimed to compare the \n electrophysiological characteristics of normal muscles versus muscles with latent or active \n myofascial trigger points , and to identify their neuromuscular physiological \n characteristics , in order to provide a quantitative evaluation of mps and clinical \n foundational data for its diagnosis .\nthis study was approved by the \n research agency , and all participants provided written informed consent .\nsubjects were \n selected among those with no known neurologic disease , no regular exercise habit , and no \n drug use that could affect the experimental result .\nsubjects in the active myofascial trigger point group were those diagnosed with mps \n by a physician and whose clinical characteristics were pain in the upper trapezius during \n rest , taut bands , tender nodules , referred pain , local twitch response , and muscle weakness . \n\nsubjects in the latent myofascial trigger point group were those not diagnosed with mps but \n who felt tenderness when the upper trapezius was stimulated .\nmean age , height , and weight , respectively , were 23.27 \n 4.21 years , 172.32 8.44 cm , and 64.14 6.54 kg in the active trigger point group ; 23.74 \n 6.47 years , 174.76 6.22 cm , and 66.74 5.74 kg in the latent trigger point group ; and \n 24.17 3.14 years , 171.21 9.64 cm , and 63.44 7.51 kg in the control group . to measure maximum voluntary isometric contraction ( mvic ) , the shoulders and heads of the \n subjects were firmly fixed and pulled as the dynamometer as maximum power , thereby measuring \n mvic against the upper trapezius .\nendurance time was measured from the start of mvic to a \n 50% reduction in contraction force .\nmedian frequency ( mdf ) was measured by using emg at the \n muscle belly of the upper trapezius during mvic .\nmuscle fatigue index was calculated by \n obtaining the mdf at a section where the mvic force was reduced from 100% to 50% , and remove \n the 50% mdf from 100% mdf was divided into 100% mdf .\nthe sampling rate for the surface emg \n signal was set at 1,000 hz , and the frequency band filter was set at 20 to 450 hz , using one \n channel .\nstorage and analysis of the emg signals was performed using acqknowledge 3.8.1 \n ( biopac systems , goleta , ca , usa ) .\nthe average of three measurements was calculated and used \n in the analyses ; 10 minutes of rest was given between measurements to prevent muscle \n fatigue .\nstatistical analyses were performed using spss version 18.0 for windows ( spss , inc . \n\none - way analysis of variance was conducted to examine differences among \n groups with respect to the measured items , while the tukey test was conducted for post hoc \n analysis .\nthere were no significant differences in mvic or endurance time among the three groups . \n however , mdf was significantly different among all three groups ( p < 0.05 ) ( table 1table 1.comparison of mvic , et , mdf , and fi among the three groupsgroup a ( n = 30)group b ( n = 30)group c ( n = 30)post hocmvic , kg19.811.5 * 22.19.423.510.2/et , s48.59.749.510.251.28.8/mdf , hz102.521.488.523.184.517.4a <\ncmfi0.150.070.080.040.060.04a < cdata are presented as mean sd . * significant difference among the three groups ( p \n < 0.05 ) .\ngroup a : active myofascial trigger points ; group b : latent myofascial \n trigger points ; group c : control .\net : endurance time ; mdf : median frequency ; mfi : \n muscle fatigue index ; mvic : maximal voluntary isometric contraction ) .\ntukey post hoc results showed that the active myofascial \n trigger point group was significantly different from the control group .\nmuscle fatigue index \n also was significantly different among all three groups ( p < 0.05 ) ( table 1 ) .\ntukey post hoc results showed \n that the active myofascial trigger point group was significantly different from the control \n group .\ndata are presented as mean sd . * significant difference among the three groups ( p \n < 0.05 ) .\ngroup a : active myofascial trigger points ; group b : latent myofascial \n trigger points ; group c : control .\net : endurance time ; mdf : median frequency ; mfi : \n muscle fatigue index ; mvic : maximal voluntary isometric contraction\nthis study aimed to measure mvic , endurance , mdf , and muscle fatigue index of normal \n muscles versus muscles with latent or active myofascial trigger points , thereby identifying \n the neuromuscular physiological characteristics of muscles with active myofascial trigger \n points and providing clinical foundational data that are applicable for the quantitative \n evaluation and diagnosis of mps .\nsurface emg , which was used to evaluate the functionality of trigger points in this study , \n is nonintrusive and convenient ; thus , it is widely used in studies on the functional \n characteristics of muscle , by analyzing the electrical activity of muscle .\nthe results of \n mdf according to surface emg show changes in recruitment of fast - twitch muscle fibers and \n conduction velocity of motor unit action potential12 .\nin addition , increases in mdf reflect recruitment of type ii \n fibers , and muscle fatigue index can be analyzed according to the relationship between type \n ii fibers and mdf13 , 14 . in the present experiment ,\nmdf was significantly higher in the \n active trigger point muscles than in normal muscles .\nthe above results indicate that as \n trigger points were activated , recruitment of motor unit action potential of type ii fibers \n also increased .\nin addition , muscle fatigue index also increased due to the increased \n distribution of type ii fibers .\nhowever , mvic was lower in active trigger point muscles than \n in normal muscles .\nalthough a high correlation between muscle strength and mdf has been \n reported15 , 16 , the same correlation was not found in this study .\nthis result was \n due to increased recruitment of motor unit action potential of type ii fibers in active \n trigger point muscles , which more easily induced muscle fatigue as a physiological \n phenomenon , thereby reducing muscle strength .\nin other words , the greater the fatigue , the \n weaker the muscle strength17 ; endurance \n also was decreased due to muscle weakening .\ntherefore , this study s results will be effective in complementing the physical therapy \n diagnosis of mps which , until now , has focused on physical examination only by understanding \n not only the usefulness of electrophysiological analysis in mps diagnosis , but also the \n neuromuscular physiological characteristics of active trigger point muscles .", "answer": "[ purpose ] this study compared the differences in electrophysiological characteristics of \n normal muscles versus muscles with latent or active myofascial trigger points , and \n identified the neuromuscular physiological characteristics of muscles with active \n myofascial trigger points , thereby providing a quantitative evaluation of myofascial pain \n syndrome and clinical foundational data for its diagnosis . [ subjects ] ninety adults in \n their 20s participated in this study . \n subjects were equally divided into three groups : the \n active myofascial trigger point group , the latent myofascial trigger point group , and the \n control group . [ methods ] \n maximum voluntary isometric contraction ( mvic ) , endurance , median \n frequency ( mdf ) , and muscle fatigue index were measured in all subjects . \n [ results ] no \n significant differences in mvic or endurance were revealed among the three groups . \n \n however , the active trigger point group had significantly different mdf and muscle fatigue \n index compared with the control group . [ conclusion ] given that muscles with active \n myofascial trigger points had an increased mdf and suffered muscle fatigue more easily , \n increased recruitment of motor unit action potential of type ii fibers was evident . \n \n therefore , electrophysiological analysis of these myofascial trigger points can be applied \n to evaluate the effect of physical therapy and provide a quantitative diagnosis of \n myofascial pain syndrome .", "id": 377} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nperforation of the biliary system occurs \n most frequently in the gallbladder , usually associated with ( and complicating \n upto 10% cases of ) acute cholecystitis .\nperforation of the extrahepatic biliary \n tree is a rare entity , accounting for less than 10% of intraperitoneal biliary \n rupture .\nbile duct perforation is most commonly described in infants related to congenital \n biliary system anomalies .\naetiology in the adult is commonly attributable to \n intramural infection , necrosis of the wall of the bile duct secondary to \n thrombosis , increased intraductal pressure secondary to obstruction , cirrhosis , \n and direct erosion by calculi .\noverall , 70% of cases are related to calculi \n . the incidence of biliary tract disease during pregnancy ranges from 0.050.3% . despite these apparent low \n figures , complications from gallstones\nrepresent the most common general surgical condition \n requiring surgical intervention , second only to appendicitis .\nindications for intervention of gallstones during pregnancy \n include obstructive jaundice , acute cholecystitis , or pancreatitis failing \n medical management .\nwe present the case of a young woman diagnosed with \n gallstones in late pregnancy , complicated by acute gallstone pancreatitis and \n subsequently spontaneous common bile duct perforation .\na twenty - year - old primigravida woman was \n planned for elective caesarean section due to breech presentation .\nthe patient \n had a past medical history of -thalassemia trait , but was not \n normally on regular medication .\nher mother had previously undergone a \n cholecystectomy for gallstones . at 34 weeks gestation , she presented \n acutely with a two - week history of worsening abdominal pain localised to the \n epigastric region , associated with vomiting . on examination ,\nblood results revealed raised inflammatory markers ( wbc 14.4 [ 4.011.0 ] , \n neutrophils 11.9 [ 2.07.5 ] , crp 60 \n [ 07.5 ] ) and evidence of pancreatitis ( amylase 1369\niu / l [ 36128 ] ) , mildly \n raised bilirubin ( 24 mol / l [ 020 ] ) and raised alkaline phosphatase ( 183\nan abdominal ultrasound revealed multiple small gallstones and a \n thickened gallbladder wall , but no evidence of a dilated intra or extrahepatic \n biliary system .\nthe patient was treated conservatively , rapidly improved , and liver function tests \n normalised .\nan emergency caesarean \n section was performed and a term baby delivered , but no obvious cause was found \n to explain her clinical condition .\nthe following day her clinical condition worsened , with progressive abdominal pain \n and a metabolic acidosis .\nshe required aggressive resuscitation , inotropic , and ventilatory support and was , \n therefore , admitted to the intensive care unit .\na computed tomography ( ct ) \n revealed extensive free peritoneal fluid and gas of which the aetiology was not \n apparent .\nthe patient underwent a prompt laparotomy and was found to have \n generalised biliary peritonitis .\nthe gallbladder was intact but a 2 mm \n perforation was found on the anterior surface of a dilated common \n bile duct ( 12 mm ) . on table\ncholangiography suggested obstruction of the distal \n common bile duct caused by a 5 mm gallstone impacted within the distal common \n bile duct . \n\nthe calculus was removed , and the duct was repaired over a t - tube .\na t - tube cholangiogram was performed \n after 4 weeks , and the tube was uneventfully removed ( figure 1 ) .\nalthough the pathogenesis of spontaneous biliary perforation is poorly understood , \n recognised mechanisms include the following : calculous perforation at the site \n of impaction ; calculous erosion without impaction ; increased canalicular \n pressure due to obstruction by tumour , stone , or spasm of the sphincter of \n oddi ; intramural infection ; mural vessel infarction leading to mural necrosis ; \n or rupture of a biliary tract anomaly such as cyst or diverticulum .\nthus , \n because perforation of the biliary system is a recognised complication of \n cholelithiasis , the diagnosis should be suspected if a perihepatic abscess or \n peritonitis is combined with biliary stone disease . as early as 1882 , freeland reported the first case of extrahepatic biliary system rupture in an adult ( diagnosed at autopsy ) , an entity that was \n subsequently first described in pregnancy by piotrowski et al . over a \n century later . since this time ,\nvery few cases of spontaneous common bile duct \n perforation in adults have been reported in the literature , with cases \n occurring during pregnancy being even more scarce .\nthe importance of this clinical \n scenario lies in the potential serious morbidity and not infrequent mortality \n associated with missed biliary system perforation .\npetrozza \n et al . described two cases of gallbladder perforation due to cholelithiasis in \n the early postpartum period .\nboth cases presented a diagnostic dilemma , and it \n was concluded that a history of cholelithiasis in a patient with persistent \n intra - abdominal symptoms in the postpartum period must alert to prompt \n investigation and early management .\n, \n one patient was found to have suffered gallbladder rupture as a result of \n cholecystitis , and in the second , a common bile duct perforation was found at \n laparotomy with no obvious precipitating cause .\n. also drew \n attention to the similarity of symptoms of gallbladder disease in pregnancy to \n mild pre - eclampsia , having in common hypertension , epigastric pain , and mildly \n deranged liver function tests .\nthese cases highlight the importance of \n recognising the possibility of delayed diagnosis of cholelithiasis as a result \n of nonspecific abdominal symptoms during pregnancy and indicate early \n investigation and treatment in order to reduce serious morbidity .\n. \n block and kelly reported the optimum time for surgical management of \n gallstone pancreatitis to be in the second trimester or early postpartum \n period , in order to minimise maternal / fetal mortality and recurrent \n pancreatitis .\nunfortunately , in those women presenting \n late in pregnancy ( as in the case described ) , the balance of risk favours \n watchful waiting until after delivery followed by elective cholecystectomy . \n certainly , this risks early recurrence of acute pancreatitis , as well as rare but severe \n consequences such as biliary peritonitis . \n whether an early endoscopic retrograde cholangiopancreaticography ( ercp ) \n and sphincterotomy in those cases presenting with gallstone pancreatitis can be \n an acceptable temporary preventive measure is unclear , but undertaking ercp is \n not without risk , and the potential risks should be considered carefully in \n individual cases . in this particular case , \n\nit is impossible to know whether the eroding calculus had been present during the \n initial episode of pancreatitis .\nmagnetic resonance scanning is a commonly used \n imaging modality in obstetrics , considered to be safe and avoiding the use of \n ionising radiation .\ntherefore , magnetic resonance cholangiopancreatography \n ( mrcp ) would have been a reasonable next investigation during this patient s \n initial presentation , and if a ductal stone had been revealed , then the indication \n for ercp may have been clearer .\non the other hand , neonatal and postnatal \n care of babies born early have progressed significantly , suggesting the \n possibility of induction of labour perhaps at 3638 weeks \n gestation in severely symptomatic or high - risk patients .\nof course , every case \n must be considered individually , taking into account maternal and fetal \n history and health .", "answer": "spontaneous perforation of the extrahepatic biliary system is a rare presentation of ductal stones . \n we report the case of a twenty - year - old woman presenting at term with biliary peritonitis caused by common bile duct ( cbd ) perforation due to an impacted stone in the distal common bile duct . \n the patient had suffered a single herald episode of acute gallstone pancreatitis during the third trimester . \n the patient underwent an emergency laparotomy , bile duct exploration , and removal of the ductal stone . \n the postoperative course was uneventful .", "id": 378} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe standard management for muscle - invasive transitional cell carcinoma ( tcc ) and non - muscle - invasive tcc of bladder with a high risk of progression is radical cystectomy with pelvic lymph node dissection .\northotopic neobladder ( onb ) substitution is an accepted form of urinary diversion after radical cystectomy with a better quality of life as compared with cutaneous urinary diversion .\nthere is a possibility of urethral recurrence after onb substitution , compromising its functional integrity .\nthe reported recurrence rate of urethra after radical cystectomy has a wide variation and ranges from 0.5% to 18% . in initial studies ,\nprostatic involvement was considered as a significant prognosticator for urethral recurrence , but later on it was shown that despite a positive endoscopic biopsy from the prostatic urethra , if the resected margin of the urethra on frozen section analysis ( fsa ) was negative , then the urethral recurrence is unlikely even after 10 years of follow - up .\nthere is paucity of data on the robustness of intra - operative fsa , influencing the decision of urinary diversion .\nmore often than not , the yield of fsa is lower than expected , and , in a majority of cases , it seems to be an unnecessary step .\nit is interesting to see that even a positive urethral margin on fsa does not predict the recurrence of tcc at the urethral stump .\nthis raises an important issue of performing a step as a routine when it may not be necessary .\nwe analyzed our data to assess the need for fsa in patients of radical cystectomy planned for onb .\nfor this institutional ethics board approved study , data on radical cystectomy performed between january 2000 and june 2013 were retrieved from the hospital information system and internal data management source of our center .\na total of 233 radical cystectomies were performed during the study period . of these ,\n, fsa was performed for presence or absence of malignancy at the urethra on the patient side .\nbased on the low yield of fsa , after 2010 , this step was not performed as a routine and only those patients who had visible growth at the bladder neck had fsa . for statistical analyses ,\npatients were grouped into three groups , i.e. patients with fsa and positive margin , patients with fsa but negative margin and those in whom fsa was not performed .\npathological characteristics of these groups were compared for local staging and presence or absence of carcinoma in situ . a contrast - enhanced computed tomography ( cect )\nimaging parameters like hydroureteronephrosis , tumor size at the time of presentation and site of the bladder tumor in relation to the bladder neck were assessed .\nlocation of the tumor in relation to the bladder neck and trigone on cect was matched with the findings on the cut - open specimen .\npatients were followed - up every 4 months with ultrasonography , serum creatinine , lower urinary tract symptoms , uroflowmetry , post - void residue and venous blood gas analysis .\nsurvival curves for patients whose fsa was negative and patients who did not have fsa were compared with the log rank test .\nbinary logistic regression analysis was performed to analyze the effect of imaging parameters on the status of the urethral margin .\nall the statistical analyses were performed using spss 16 ( chicago , il , usa ) .\nsurvival curves for patients whose fsa was negative and patients who did not have fsa were compared with the log rank test .\nbinary logistic regression analysis was performed to analyze the effect of imaging parameters on the status of the urethral margin .\nall the statistical analyses were performed using spss 16 ( chicago , il , usa ) .\nsurvival curves for patients whose fsa was negative and patients who did not have fsa were compared with the log rank test .\nbinary logistic regression analysis was performed to analyze the effect of imaging parameters on the status of the urethral margin .\nall the statistical analyses were performed using spss 16 ( chicago , il , usa ) .\nthe mean age of 151 patients who were planned for onb was 56.3 10.7 years .\nof those 109 patients , only three ( 2.7% ) patients had a positive urethral margin .\ntwo of them had ileal conduit diversion and one patient , after having a negative biopsy on the second fsa , had onb .\nalthough none of the factors , i.e. hydroureteronephrosis , tumor size and site , were found to be significant for predicting urethral margin status , all three patients with a positive urethral margin had tumor encroaching the bladder neck [ figure 1 ] .\nall the patients with a positive urethral margin died of cancer at a mean follow up of 29.33 18.3 months , but none had urethral recurrence till the time of death .\npatients who died of cancer had pelvic and/or distant metastasis . pathological characteristics of the patients according to the urethral margin status outcome of the patients according to the frozen section analysis ( fsa ) of the urethral margin one of the patients with a positive urethral margin who had tumor involving the bladder neck ( blue solid arrow ) overall , 34/151 ( 22.5% ) patients had growth at the bladder neck on cect . of these , six tumors were actually found to be away from the bladder neck on the cut - open specimen .\n[ figure 2 , table 3 ] the false - positive report of bladder neck involvement on cect was 18% , ( six of 34 cases ) .\ntherefore , only 28/138 ( 21.5% ) patients had growth at the bladder neck [ table 3 ] .\nof these 28 patients , three ( 10.7% ) had a positive urethral margin and all these three patients had tumor involving the bladder neck .\ntumor involving the bladder neck on the contrast - enhanced computed tomography scan was found to be away from the bladder neck in the cut - opened specimen ( white solid arrow ) comparative results of bladder neck involvement found on cect and during naked eye examination in the surgical specimen regarding association of the urethral margin with the involvement of the prostate , it was found that of 141 male patients , 10 ( 7% ) had their prostate involved but none had a positive urethral margin [ table 4 ] .\nsimilarly , two male patients who had a positive urethral margin had no prostatic involvement .\nlocation of the tumor at the bladder neck did not correlate with the involvement of the prostate ( p = 0.983 ) [ table 4 ] .\nrelationship between location of the tumor and the involvement of the prostate gland ( n=128 ) the 1- and 5-year overall survival of patients with negative fsa were 91.5% ( 95% ci , 8593.5 ) and 79% ( 95% ci , 7284% ) , and of those in whom fsa was not performed were 93% ( 95% ci , 8695% ) and 82% ( 95% ci , 7489% ) .\n[ figure 3 ] the mean follow - up times were 46.3 25.1 months and 36 9.3 months for the frozen section negative and not sent groups , respectively .\nnone of the patients without fsa ( 42 ) had urethral recurrence at a mean follow - up of 36 9.3 months .\nmeir survival curve with log rank test comparing survival in patients with negative urethral margin and in patients in whom frozen was not sent only two patients had recurrence in the penile urethra : one patient after 6 years and the other patient 2 years following onb . in both the cases ,\nthe urethral biopsy was positive for malignancy but the neo bladder urethral junction was normal .\nthe gold standard treatment for muscle - invasive or recurrent transitional carcinoma of the urinary bladder is radical cystectomy with urinary diversion . among the various kinds of urinary diversions ,\nonb substitution provides the most natural way to void , with a relatively better quality of life .\nthe whole purpose of using an external sphincter as a continent mechanism for onb would be defeated if there is recurrence in the urethra .\ntherefore , it is a standard practice to send the urethral margin for fsa before performing onb to ensure that the urethral margin is negative . the reported rate of urethral recurrence after radical cystectomy has a wide variation , ranging from 0.5% to 18% .\nas recurrence at the urethral stump is known even after having a negative margin , it seems likely that the reason for recurrence is not the status of margin assessed by the available means . according to early reports ,\nthe most consistent risk factor in men for predicting urethral recurrence was the involvement of the prostate .\nalthough urethral recurrence was not common in patients with prostatic urethral involvement , prostatic ductal and stromal involvement were associated with the urethral recurrence , ranging from 10% to 67% .\nsimilarly , women with tumors located at the bladder neck or involving the anterior vaginal wall are at a higher risk for urethral recurrence .\nlater on , onb substitution was perfromed even in patients who had involvement of the prostatic urethra ( confirmed on endoscopic biopsy ) , provided the fsa showed a negative urethral margin .\nafter a minimum follow - up of 10 years , none of the patients had urethral recurrence . in another study of a similar kind , the positive and negative predictive values of the prostatic urethral biopsy prior to cystectomy were 12% and 99.9% , respectively .\nthey concluded that presence of tumor in the prostatic urethra prior to cystectomy would not preclude orthotopic neobladder substitution if the urethral frozen section is negative .\nfollowing these studies , intraoperative frozen section biopsy of the urethral margin became the pre - requisite for an onb , disregarding the status of prostatic involvement .\ninterestingly , that the rate of urethral recurrence in patient undergoing onb has been found to be low .\nalthough these studies are retrospective in nature , where bias of choosing a case with better tumor characteristics could be the reason , the inexplicable protective effect of onb against recurrence at the urethral margin is quite evident .\npublished their series and concluded that patients with onb have a lower risk of urethral recurrence than those who had cutaneous urinary diversion for tcc urinary bladder .\nthis protective effect of onb for urethral recurrence was also demonstrated by stein et al .\nalthough one would argue against not performing fsa , one needs to assess the overall impact of fsa in terms of decision making for or against the onb .\nurethral recurrences have also been reported with the negative urethral margin , the incidence of which has been described to range from 0.9% to 2.8% . in one series , two of 13 patients with positive fsa had urethra recurrence as opposed to 13 recurrences in 222 patients who had negative fsa .\ntherefore , the urethral margin status failed to accurately predict recurrence at the urethral stump . in the present study too , we had a very low yield of frozen section biopsy , wherein we had only 2.7% of positive fsa .\nall three patients died of their disease , but none had urethral recurrence at the time of death . among the survivors also , we had only two urethral recurrences at the mid penile urethra , and both the patients had negative fsa as well .\nlooking at the recurrence rate of less than 3% at the urethral stump and low positive predictive value of the frozen section , should we be performing fsa in all the patients ?\nmoreover , an overall survival in patients where frozen was not sent was not different from those in whom frozen was sent and had a negative urethral margin .\ninterestingly , in our study , although the location and size of the tumor and hydroureteronephrosis did not predict the status of the urethral margin , three patients who did have a positive urethral margin had tumors located at the bladder neck . in our experience ,\ncarcinoma in situ ( cis ) changes are not found as frequently as reported in the literature ; moreover , normal - looking mucosa on cystoscopy is unlikely to have cis changes .\nnone of the patients who had tumor away from the bladder neck showed a positive margin , and about 77.5% of our patients had growth away from the bladder neck .\nthe cut - section of the specimen immediately after the cystectomy is a useful way to determine the location of the growth at the neck , as six of 34 ( 18% ) cases had a false - positive report on cect scan .\ninvolvement of the prostate in the radical cystectomy specimen in the present study was just 7% , as against 17% in one of the largest series on radical cystectomy .\nnone of the patients with prostatic involvement in the present series had a positive urethral margin , which contradicts the theory of synchronous involvement of the urethra .\nvisual impression of the specimen to determine the encroachment of tumor to the bladder neck , similar to the one we apply during partial nephrectomy , could be helpful in deciding against sending a routine frozen section\n. limitations of the study are relatively less number of patients with positive urethral margin and relatively short follow - up of those in whom we did not send the frozen section .\nthis study questions the ubiquity of performing a step that is unlikely to help in decision making . in the majority of cases\n, fsa seems to be an unnecessary step and mere visual impression of the tumor and urethra could be helpful in deciding about sending the urethral margin for fsa .\nonly patients who have growth located at the bladder neck on the cut - open specimen should have fsa .", "answer": "introduction : this study was aimed at analyzing the need for routine use of frozen section analysis ( fsa ) before performing orthotopic neobladder ( onb ) after radical cystectomy for carcinoma urinary bladder.materials and methods : a total of 233 patients underwent radical cystectomy from january 2000 to june 2013 . \n of these , 151 ( 65.6% ) patients were planned for onb . in the initial 109 ( 72% ) patients , \n fsa of urethral margin was performed , but , in the subsequent 42 ( 28% ) patients , frozen section of urethral margin was not sent . \n impact of hydroureteronephrosis , tumor size and location of tumor in relation to the bladder neck on the status of the urethral margin was analyzed.results:only three of the 109 ( 2.7% ) patients had a positive urethral margin . \n two of them had ileal conduit and one , after negative re - resection , had onb . \n although none of the factors was found to be significant , all three patients with a positive urethral margin had growth at the bladder neck and died of cancer at a mean follow up of 29.33 18.3 months , without urethral recurrence . among the negative fsa ( 106 ) , two patients had recurrence in the penile urethra . \n the mean follow - up was 46.3 25.1 months . \n none of the patients without fsa ( 42 ) had urethral recurrence at the mean follow - up of 36 9.3 months . \n of the 28 patients who had their growth located at the bladder neck , three had positive fsa , while none with growth away from the bladder neck had positive fsa.conclusion:routine fsa of the urethra before performing onb can be avoided in those patients where the tumor does not reach the bladder neck .", "id": 379} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nPermuting Diels-Alder and Robinson Annulation Stereopatterns\n\nPaper sections:\nIntroduction\nSynthetic planning directed to conjugated octalones, of the type 1, traditionally tends to center around enolate and enol based progressions inherent in the expression \"Robinson Annulation\" (RA, see eq. 1).1,2,3 By contrast, nonconjugated octalone systems of the type 2 are perceived as likely to arise from a Diels-Alder based cycloaddition logic (DA, eq. 2).4,5,6,7\n(1)\n(2)
Not surprisingly, these widely used synthetic platforms lead to differing biases in diastereoselection. For instance, consider the consequences of these modalities for orchestrating a 1,4 stereorelationship in a bicyclic product arising from two kinds of cyclohexene substrates \u2013 an enolate (3) and an enone (5). In the R A m o d e , diastereofacial induction tends to be stereoelectronically, rather than sterically, driven for the RA progression.8 Thus, if enolate alkylation occurs in the preferred axial sense, with the resident C5 group (asterisk) equatorial, formation of an \"anti product,\" of the type 4 would be favored.9,10 By contrast, in the DA modality, preferred combination of the DA diene with 5 would tend to occur anti to the R group, leading to a \"syn\" type product (6).11\n(3)\n(4)
These differing stereopatterns are also associated with strikingly different displays of the key functional groups (olefin and ketone) in the bicyclic products (compare octalones 1 and 2). Given this situation, we addressed the question as to whether the conventional structural and diastereoselection tendencies can be exploited such that a DA \"stereopattern\" might be transmitted to a typical RA type product.
Recently, we described a somewhat fortuitous discovery, wherein the double bond of a Diels-Alder derived octalone of the type 7 can be isomerized under mediation by silica gel to afford 8 (Scheme 1).12,13 The latter type of structure is easily seen to be a double bond isomer of a standard Diels-Alder cycloaddition product. It could well be anticipated that Saegusa-Ito-type oxidation14,15 of 8 would give rise to 9, in which a DA stereochemical pattern is ensconced in an RA functional group arrangement (i.e. the expected \"wild-type\" RA stereomotif would be that shown in 10).
Attention has already been drawn16 to the potential value of pattern recognition analysis (PRA) as a resource in the planning of the synthesis of complex targets. While the compelling logic of prioritized strategic bond disconnection, advanced by Corey and associates many years ago,17,18 still lies at the heart of contemporary retrosynthetic analysis, PRA, which seeks out identifiable holistic substructural domains, may provide a complementary venue for forward planning.16 Thus, the question we posed above, concerning the permutability of the diastereoselectivity biases of these key reaction types, has the potential to offer new avenues for synthetic planning, particularly in subtle issues of stereochemistry (vide infra, syntheses of carissone19 and of the reported structure of cosmosoic acid20).
\n\nResults and Discussion\nAs shown in Scheme 2, we began our inquiry by demonstrating how two mainstay products of classical RA-based strategies, the Hajos\u2013Parrish ketone (13)21 and the Wieland\u2013Miescher ketone (14),22 could be synthesized in quite reasonable overall yields from the easily available, appropriate \u03b1-methylcyclenones.23,24 Of course, in the particular cases of 13 and 14, there were no issues of relative stereochemistry to be addressed. Though we have not yet pursued the matter, enantioselectivity could, in principle, be realized from a catalyst that can impose absolute stereochemical guidance at the stage of the [4+2] cycloaddition event.
We next turned to cases bearing C4 substitution on the dienophilic cyclenone substrate. As shown in Scheme 3, the facial stereoselection of the cycloaddition reaction is high (>10:1).25 At this writing, the ratio of \u03942:\u0394 3 regioisomers in the double bond migration step in this series was somewhat disappointing.26,27 While the precise factors governing the selectivity of isomerization remain to be determined, they may well reflect minimization of peri interactions between C4 and C6 in the isomerized structure. Fortunately, we were able to retrieve the un-rearranged material and re-subject it to isomerization, thus improving our material throughput. Saegusa-Ito oxidation14,15 proceeded well to afford 17a and 18, respectively. That epimerization had not occurred at C6 during this step, was shown in the case of 17a by its non-identity with compound 17b, previously described and assigned in a rigorous way by Grieco and co-workers.28,29 Subjection of compound 17a to equilibrating conditions did, indeed, lead to epimerization, with emergence of 17b. Thus, the chemistry described above does lead to the otherwise difficultly accessible 6-axially alkylated \u03944 3-octalones.
This chemistry was next extended to a situation where the substituent on the cyclohexenone dienophile appears at C5. Four cases were examined (Table 1). As seen, the cycloadditions were, again, highly stereoselective, providing substantially one isomer in the Diels-Alder reaction.25 Again, silica gel mediation of the double bond isomerization occurred quite smoothly, this time in higher ratios than those contained in the 4-substituted series. Once again, Saegusa-Ito oxidations14,15 delivered the target octalones, this time bearing a substituent at C7,26\ncis to the junction methyl group. This type of series is not readily generated from classical Robinson annulation strategies.
Adding to the patterns accessible by this logic was the fact that the chemistry is also extendable to the situation where the Diels-Alder diene contains a methyl substituent group at a terminal carbon30 (Table 2). Once again, the levels of face selectivity in the cycloadditions were excellent, giving rise to the major adducts shown. Silica gel mediated isomerizations afforded the \"iso-DA-type\" products in high ratios relative to starting DA adducts. Following Saegusa oxidation, there were obtained the octalones 33, 35, and 37 with a cis relationship between the junction (C10) and the C6 or C7 substituents.26 As discussed above, this stereopattern is not readily obtained from Robinson annulation strategies, either due to epimerization, in the case of the 6-substituted product, or because of the stereoelectronics of alkylation which govern the case where the substituent is at C7.
The applicability of this permuting of RA:DA logic was demonstrated in the context of two total synthesis programs. As will be seen, the targets were selected to exemplify the enhanced possibilities enabled by the chemistry described above. It was for the purpose of synthesizing the sesquiterpene carissone that we conducted the Diels-Alder reaction of 38 with 19.19,31 As shown in Table 2, cycloadition of 38 and 19 gave rise to a cycloadduct which underwent silica induced double bond isomerization, followed by Saegusa oxidation14 to afford 35. Not surprisingly,32 selective reduction of the non-conjugated ketone (C9) could readily be achieved to afford an alcohol (39), which, upon Barton deoxygenation,33 gave rise to 40. Deprotection, as shown, afforded (+)-carissone (41). We note that an elegant total synthesis of (+)-carissone, that does not draw from the chiral pool, has recently been described by Stoltz and colleagues.34 In the Stoltz synthesis, the C7\u2013C10 stereorelationship was also managed through a non-RA program.
Recently, we noted a disclosure in the literature describing the isolation of a compound called cosmosoic acid (42)20 from Cosmos sulphureus, a plant native to Brazil and Mexico. This plant had been identified as a source of anti-malarial natural products, although antimalarial properties of 42, per se, were not reported. The gross structure and stereochemistry of cosmosoic acid had been determined strictly by spectroscopic methods, not supported by any degradative or crystallographic investigations.20 Given the Pattern Recognition Analysis line of thinking,16 one immediately notes the \"iso-Diels-Alder\" characteristic of cosmosoic acid.35 In this context, C3 of the C3\u2013C4 iso-DA pattern carries a carboxyl group. One might well have considered synthesizing cosmosoic acid by a Diels-Alder reaction of diene 4336 with the generic dienophile 44, followed by isomerization of 45. To us, it seemed that such a program presented unlikely prospects for success. First, dienes of the type 43 tend to be quite unstable.37 Furthermore, the electron withdrawing carboxyl group at C2 would render this diene even less reactive in a hypothesized DA cycloaddition4-6 with an electron withdrawing dienophile of the type 44. Moreover, the key silica gel\u2013mediated isomerization reaction has not been demonstrated in the context of octalin-related DA adducts arising from cycloadducts of the type 45. Instead, we preferred to resort to our usual 2-siloxybutadiene DA building block. If cycloaddition and isomerization would occur with appropriate selectivities, success would depend on converting the subsequently tautomerized ene-siloxy function in 47 to the corresponding unsaturated acid.
In the event, reaction of siloxydiene 4638 with the enone 4439 occurred quite smoothly in the presence EtAlCl2 to provide 49 in 90% yield. Happily, the silica gel\u2013mediated isomerization of 49 proceeded, providing the isomerized silylenol ether (see 47). It seemed prudent to protect the ketone in the light of subsequent operations which were planned (vide infra). Remarkably, it was possible to convert the ketone function of 47 to its corresponding enol ether derivative, 50, via deprotonation with LDA and O-methylation with dimethyl sulfate. This method is not a common one for generating methyl enol ethers from ketones and could warrant future research as to its scope.
With compound 50 in hand, we turned to the conversion of the silylenol ether to the corresponding vinyl triflate. In the event, this subgoal was accomplished by generating the corresponding site-specific enolate via the action of 50 with methyllithium,40 whereupon quenching with the Comins reagent41 afforded the corresponding vinyl triflate 51. With compound 51 in hand, we examined the possibility of a modified Heck-carbonylation.42 Happily, this subgoal was accomplished relatively smoothly (75% yield) under the conditions shown. The intermediate acid was converted to its methyl ester 52. Hydrolysis of the enol ether function gave rise to ketone 53 in an overall yield of 75%. Saponification of the methyl ester gave rise to a product, tentatively assigned as structure 42.
Surprisingly, the NMR spectrum of presumed 42, thus obtained, exhibited certain clear differences from the NMR spectrum reported for cosmosoic acid.43 Obviously, we had reason to be concerned about a possible structural mis-assignment on our part, somewhere during our synthetic work. Upon reexamination of the intermediates generated in the total synthesis progression and our assignments along the way, we remained convinced that we had in fact synthesized 42 as shown. Happily, the matter was objectively established by an X-ray crystal structure of the synthetic material, which clearly revealed the end product of our total synthesis to be compound 42.44 At this stage, it seemed very likely that the structure of the natural product cosmosoic acid does not correspond to that shown in 42. Several attempts were made to network with the original authors,20 but these efforts did not provide any additional insight. No helpful samples or spectral readouts were obtained.
At the time of writing, we can only conclude that the structure of cosmosoic acid does not correspond to 42. Having no access to the natural product, itself, we are unable to provide an informed opinion as to the correct structure of naturally occurring cosmosoic acid.
Finally, we examined substitutions at C6 of the cyclohexenone (which would correspond to C8 of the resulting octalone26). In this connection we studied the case of compound 54.45 Attempted cycloadditions of 54 with diene 46 resulted in approximately 1:1 mixtures.46 Thus, the stereoguidance that we had successfully encountered in the cases of the 4- and 5-substituted 2-methylcyclohexenones, apparently does not provide useful margins with the 6-substituted system (cf. 54).25 This, in itself, is perhaps not surprising in the light of the nature of the Diels-Alder reaction.4-6 In the cycloaddition of a compound such as 54, one envisions the initial orienting bonding would occur at C3 of the cyclohexenone, and slightly later at C2 in the imperfectly concerted cycloaddition. That being the case, the methyl group at C6 would be only weakly directing, since it is in a 1,4-relationship to the emerging \"lead\" bond.
\n\nConclusion\nIn summary, we have demonstrated modalities for permuting the stereochemistry and gross structural patterns emerging from a classical Robinson annulation (RA), with Diels-Alder (DA)-based technologies. The line of reasoning has led to stereospecific syntheses of carissone and the previously assigned structure of cosmosoic acid. In the latter case, the total synthesis work suggests that the structural assignment of the natural product is in error. We are hopeful that the successful demonstrations provided above for broadening the accessible relationships applicable to PRA can be applied to interchanging the structural and stereomotifs of other reaction dualities.
", "answer": "Controlled isomerization of the double bond of certain Diels-Alder reactions provides substrates that, upon oxidation, give rise to products whose gross structure corresponds to that of a Robinson annulation. In these cases, the stereochemistry of the Robinson annulation product reflects the fact that the initial combination occurred in a Diels-Alder mode. Using these principles, we have synthesized carissone and cosmosoic acid. In the latter case, our total synthesis raised serious questions as to the accuracy of the assigned structure of the natural product.", "id": 380} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbriefly , poly(-caprolactone ) ( pcl ) were dissolved at 143 mg / ml in equal parts tetrahydrofuran and n , n - dimethylformamide , then extruded at 2.5 ml / h through a spinneret charged to + 13 kv .\nthe resulting nanofibrous jet was collected on a grounded mandrel rotating at 10 m / s and located 20 cm from the spinneret .\naluminum shields on either side of the spinneret were charged to + 9 kv to focus the jet . the spinneret was fanned back and forth to ensure uniform fiber deposition .\nmscs were isolated from femoral and tibial bone marrow of 3 - 6 month old calves and expanded to passage 2 as described previously .\nscaffolds were hydrated by sequential washes in 100 % , 70 % , 50 % and 30% ethanol and finally phosphate buffered saline ( pbs ) . before seeding ,\n50 l of cell solution ( 1 10 cells / ml ) were applied to one side , followed by incubation at 37c for one hour .\nscaffolds were then turned and an additional 50 l of cell solution applied to the other side .\nafter two hours further incubation , samples were transferred to chemically defined media ( dmem , 0.1m dexamethasone , 40 g / ml lproline , 100 g / ml sodium pyruvate , 1% insulin , transferrin , selenium / premix , and 1% penicillin , streptomycin and fungizone supplemented with 10 ng / ml transforming growth factor 3 ) . media was replaced twice weekly for the duration of the study . after measuring cross - sectional area using a custom laser device , samples ( n=5 ) were clamped with serrated grips and loaded into an instron 5542 testing device .\nall testing was performed in a pbs bath . the mechanical testing protocol consisted of : ( 1 ) a nominal tare load of 0.1n applied at 0.1% strain / sec , followed by stress relaxation for 5 minutes , ( 2 ) 15 preconditioning cycles to 0.1% strain at 0.05% strain / sec , and ( 3 ) a quasi - static elongation at 0.1% strain / sec until failure .\nstrain was determined as extension normalized to gauge length ; stress was computed as the load normalized to initial cross - sectional area .\nmodulus was computed as the slope of the stress - strain plot , determined by regression to the linear portion of the curve . for biochemical analyses ,\nsamples were digested for 16 hours in papain at 60c , then analyzed for s - gag content using the 1,9-dimethylmethylene blue dye - binding assay , for orthohydroxyproline ( ohp ) content ( after acid hydrolysis ) to determine collagen content by reaction with chloramine t and dimethylaminobenzaldehyde , and for dna content using the picogreen dsdna quantification kit .\nohp content was converted to collagen with a ratio of 1 : 7.14 ( ohp : collagen ) .\nparaformaldehyde - fixed sections were stained for cell nuclei ( 40,6-diamidino-2-phenylindole , dapi ) , glycoasaminoglycans ( alcian blue ) and collagen ( picrosirius red ) .\ndapi - stained sections were visualized at 20 on a nikon t30 inverted fluorescent microscope .\nquantitative polarized light microscopy was performed on picrosirius red stained sections to quantify collagen alignment as described previously .\nbriefly , grayscale images were collected ( 20 ) at 10 increments using a green bandpass filter ( bp 546 nm ) with crossed analyzer and polarizer coordinately rotated through 90. this was repeated with the filter replaced by a compensator .\ncustom software was then used to determine collagen fiber orientations for a series of nodes within the central portion of each region of interest .\nnanofibrous scaffolds of approximately 1 mm thickness were prepared as above and excised along the fiber direction .\ntwo weeks of after seeding with mscs , samples ( n=5 ) were placed in apposition with a 20 mm overlap and secured with porous polypropylene and foil and cultured as above .\nlap tests were performed by gripping the overhang on either end of the bilayer and extending to failure at 0.2 mm / s .\naligned nanofibrous scaffolds of approximately 1 mm thickness were excised at 30 from the fiber direction .\nagarose was dissolved in pbs at 2 , 4 , 5 , and 6% w / v and melted by autoclaving .\nmolten agarose was applied between layers of scaffold , and allowed to set at room temperature .\nno significant difference was observed in cross sectional area across all concentrations , indicating controlled , reproducible interface formation .\nsignificance was established by p 0.05 as determined by two - way anova with a tukey 's post hoc test for independent variables of bilayer orientation ( parallel / opposing ) and culture duration ( or agarose concentration ) .\nbriefly , poly(-caprolactone ) ( pcl ) were dissolved at 143 mg / ml in equal parts tetrahydrofuran and n , n - dimethylformamide , then extruded at 2.5 ml / h through a spinneret charged to + 13 kv .\nthe resulting nanofibrous jet was collected on a grounded mandrel rotating at 10 m / s and located 20 cm from the spinneret .\naluminum shields on either side of the spinneret were charged to + 9 kv to focus the jet . the spinneret was fanned back and forth to ensure uniform fiber deposition .\nmscs were isolated from femoral and tibial bone marrow of 3 - 6 month old calves and expanded to passage 2 as described previously .\nscaffolds were hydrated by sequential washes in 100 % , 70 % , 50 % and 30% ethanol and finally phosphate buffered saline ( pbs ) . before seeding ,\n50 l of cell solution ( 1 10 cells / ml ) were applied to one side , followed by incubation at 37c for one hour .\nscaffolds were then turned and an additional 50 l of cell solution applied to the other side .\nafter two hours further incubation , samples were transferred to chemically defined media ( dmem , 0.1m dexamethasone , 40 g / ml lproline , 100 g / ml sodium pyruvate , 1% insulin , transferrin , selenium / premix , and 1% penicillin , streptomycin and fungizone supplemented with 10 ng / ml transforming growth factor 3 ) . media was replaced twice weekly for the duration of the study .\nafter measuring cross - sectional area using a custom laser device , samples ( n=5 ) were clamped with serrated grips and loaded into an instron 5542 testing device .\nall testing was performed in a pbs bath . the mechanical testing protocol consisted of : ( 1 ) a nominal tare load of 0.1n applied at 0.1% strain / sec , followed by stress relaxation for 5 minutes , ( 2 ) 15 preconditioning cycles to 0.1% strain at 0.05% strain / sec , and ( 3 ) a quasi - static elongation at 0.1% strain / sec until failure .\nstrain was determined as extension normalized to gauge length ; stress was computed as the load normalized to initial cross - sectional area .\nmodulus was computed as the slope of the stress - strain plot , determined by regression to the linear portion of the curve . for biochemical analyses ,\nsamples were digested for 16 hours in papain at 60c , then analyzed for s - gag content using the 1,9-dimethylmethylene blue dye - binding assay , for orthohydroxyproline ( ohp ) content ( after acid hydrolysis ) to determine collagen content by reaction with chloramine t and dimethylaminobenzaldehyde , and for dna content using the picogreen dsdna quantification kit .\nohp content was converted to collagen with a ratio of 1 : 7.14 ( ohp : collagen ) .\nparaformaldehyde - fixed sections were stained for cell nuclei ( 40,6-diamidino-2-phenylindole , dapi ) , glycoasaminoglycans ( alcian blue ) and collagen ( picrosirius red ) .\ndapi - stained sections were visualized at 20 on a nikon t30 inverted fluorescent microscope .\nquantitative polarized light microscopy was performed on picrosirius red stained sections to quantify collagen alignment as described previously .\nbriefly , grayscale images were collected ( 20 ) at 10 increments using a green bandpass filter ( bp 546 nm ) with crossed analyzer and polarizer coordinately rotated through 90. this was repeated with the filter replaced by a compensator .\ncustom software was then used to determine collagen fiber orientations for a series of nodes within the central portion of each region of interest .\nnanofibrous scaffolds of approximately 1 mm thickness were prepared as above and excised along the fiber direction .\ntwo weeks of after seeding with mscs , samples ( n=5 ) were placed in apposition with a 20 mm overlap and secured with porous polypropylene and foil and cultured as above .\nlap tests were performed by gripping the overhang on either end of the bilayer and extending to failure at 0.2 mm / s .\naligned nanofibrous scaffolds of approximately 1 mm thickness were excised at 30 from the fiber direction .\nagarose was dissolved in pbs at 2 , 4 , 5 , and 6% w / v and melted by autoclaving .\nmolten agarose was applied between layers of scaffold , and allowed to set at room temperature .\nno significant difference was observed in cross sectional area across all concentrations , indicating controlled , reproducible interface formation .\nsignificance was established by p 0.05 as determined by two - way anova with a tukey 's post hoc test for independent variables of bilayer orientation ( parallel / opposing ) and culture duration ( or agarose concentration ) .", "answer": "successful engineering of load - bearing tissues requires recapitulation of their complex mechanical functions . given the intimate relationship between function and form , biomimetic materials that replicate anatomic form are of great interest for tissue engineering applications . \n however , for complex tissues such as the annulus fibrosus , scaffolds have failed to capture their multi - scale structural hierarchy . \n consequently , engineered tissues have yet to reach functional equivalence with their native counterparts . here \n we present a novel strategy for annulus fibrosus tissue engineering that replicates this hierarchy with anisotropic nanofibrous laminates seeded with mesenchymal stem cells . \n these scaffolds directed the deposition of organized , collagen - rich extracellular matrix that mimicked the angle - ply , multi - lamellar architecture and achieved mechanical parity with native tissue after 10 weeks of in vitro culture . \n further , we identified a novel role for inter - lamellar shearing in reinforcing the tensile response of biologic laminates , a mechanism that has not previously been considered for these tissues .", "id": 381} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npulmonary artery aneurysms and pseudoaneurysms are uncommon ; most are caused by infections , like tuberculosis , vasculitis ( behet 's syndrome ) or trauma , often iatrogenic ; less common causes include pulmonary hypertension , congenital heart disease , lung carcinoma , and connective tissue disease ( 1 - 3 ) . because of potential risk of high mortality , secondary to pseudoaneurysm enlargement and rupture , prompt\nwe , hereby , describe a case of ascending branch of the left pulmonary artery pseudoaneurysm , following a left upper lobectomy , for which a transcatheter endovascular embolisation of the aneurysm with intra - aneurysmal n - butyl 2-cyanoacrylate ( glue ) injection was performed .\na 30-year - lady had been presented to us 3 months ago with multiple episodes of hemoptysis and one major episode of 400 cc , and gave us a history of intermittent fever , cough , breathlessness and chest pain for a period of 2 - 3 months .\nshe was a known case of pulmonary tuberculosis with left upper lobe fungal ball ( pulmonary aspergillosis ) for the past 7 years .\nshe had had complete a course of anti - tuberculosis therapy and was asymptomatic until this period when she was presented to us with hemoptysis . at this time\nthe patient visited an emergency department again a month ago for exacerbation of the above symptoms .\nbecause of the recurrent symptoms and deteriorating pulmonary function test results , the left upper lobectomy for pulmonary aspergilloma was performed .\nthe inferior pulmonary ligament was excised in order to enable the lower lobe to occupy the entire left thoracic cavity .\nthe early postoperative period was uneventful . in the third post - operative week , she started having streaky hemoptysis .\nfibre optic bronchoscopy detected a normal tracheobronchial tree , however , the left upper lobe surgical closure site was congested and inflamed .\nthough the white blood cell count was normal , the patient was treated for a presumed chest infection .\nthe patient had spotty hemoptysis for the next two weeks , until she developed 2 - 3 episodes of massive hemoptysis of about 400 - 500 cc of blood .\npatient was intubated and emergency computed tomography ( ct ) pulmonary angiography was done , which revealed a large pseudoaneurysm of the ascending branch of the left pulmonary artery ( fig .\nbecause of the patient 's severe pulmonary insufficiency , she was not a surgical candidate and was referred to us for endovascular embolisation . under local anesthesia , with anesthetists standing by for emergency resuscitation if need arise , pulmonary angiography with 5 fr , 110-cm pigtail catheter ( cordis , johnson & johnson , new jersey ) was introduced via the right femoral venous approach , which showed approximately 3.5 cm aneurysm arising from the ascending branch of the left pulmonary artery , shortly after its origin ( fig .\nthen , a 5 fr , 100-cm head hunter catheter ( cordis , johnson & johnson , new jersey ) was introduced into the feeding artery of the aneurysm , just short of the aneurysm sac .\ninitially , we tried to occlude the feeding vessel with 35 - 5 - 5 and 35 - 8 - 8 coils ( cook , bloomington , in , usa ) , but both of these coils got misplaced proximally in the lateral basal and lower lobe trunk arteries , respectively .\nbecause of larger diameter of the coils than the caliber of these arteries , the misplaced coils got stuck in a proximal part of the arteries . on an angiogram , we could see the uninterrupted rapid blood flow through the coils to the lower branches .\nfurther , with digital road mapping , 5 fr head hunter catheter in the feeding artery , and acting as a guiding catheter , the aneurysm sac was catheterized with a 2.7 fr microcatheter ( terumo progreat ; terumo deutschland gmbh , germary ) .\nnow we decided to occlude the aneurismal sac by completely filling the sac with n - butyl 2-cyanoacrylate ( glue ) injection .\nwe calculated the volume of the glue mixture required in order to fill the aneurysm cavity by slowly calculating the volume of contrast injected , without causing the reflux of the contrast into the normal pulmonary circulation proximally .\nthe volume required was approximately 4 cc . to prevent a reflux , 5 cc of higher concentration i.e. 75% glue mixture of histoacryl ( braun , melsungen , germany ) and iodized oil ( lipiodol , andre guerbert , aulnay sous bois , france ) was taken in a 5-ml luer - lock syringe\n, however we could only inject approximately 1.5 cc of the glue , as the microcatheter got blocked .\ncatheter sticking or breakage did not occur during the process of catheter retrieval and was immediately flushed vigorously with 5% dextrose to reopen the lumen .\ncheck angiogram showed the glue cast in the central part of the aneurysm sac with aneurysm still filling in the periphery ( fig .\nwe now attempted to occlude the feeding artery with coil , but this time , the coil got dislodged in the aneurysmal sac .\nnow , the angiographic picture was much clearer , and on correlating with ct saggital reconstructed images , we got to know that the length of the feeding artery to the pulmonary artery aneurysm ( pap ) sac was very short .\nso now , not to compromise the pulmonary circulation , we did not have any other option except to fill the sac either with coils or liquid materials .\nin order to be economical on the cost , as well as our past experience with the glue , we decided to occlude pap with intra - aneurysmal injection of the glue .\nwe introduced the previously used microcatheter into the sac , and this time , we used 50% glue mixture and were able to fill the sac completely with calculated volume of 3 cc of liquid mixture without spillage into the proximal normal circulation .\npost embolisation check angiogram showed a complete obliteration of the aneurysm sac with anterior ascending branch , and other branches of the left pulmonary artery being patent ( fig .\nthere was no alteration in the blood flow through the coils into the lower lobe branches , and therefore , we did not try to retrieve the coils .\nct performed on the 6th day showed glue cast with no filling of the aneurysm .\nhowever , after being asymptomatic for 2 months , she presented again to our hospital with a single episode of 300 cc of hemoptysis .\nemergency ct was performed , which did not show the new aneurysm or refilling of the previously embolised aneurysm ( fig .\n1 g ) ; however , at this time , we could see a new aspergilloma in lateral basal segment of the lower lobe , and rib osteomyelitis ( fig .\nat present , she is still admitted and is on a conservative management and being further investigated for these new ct findings .\npulmonary artery aneurysms and pseudoaneurysms ( paps ) are rare ; most are caused by infections , like tuberculosis , vasculitis ( behet 's syndrome ) or trauma , often iatrogenic , especially after swan ganz catheter insertion ; and less common causes include pulmonary hypertension , congenital heart disease , lung carcinoma , and connective tissue disease ( 1 - 3 ) .\nthus , any destructive process of the lung , whatever its pathogenesis , can erode the vessels in its vicinity , be it a pulmonary or systemic vessel .\nthe etiology in this case can be attributed to inadvertent insult to the pulmonary artery during surgery for pulmonary aspergilloma .\nalso , after lobectomy , significant increase in the pulmonary vascular resistance index has been described in the literature ( 4 ) , and this could have had a possible contributory role for the development of the pseudoaneurysm .\nanother cause could be a low grade infection of the already weakened upper lobe pulmonary arterial wall , though the blood investigations were normal in our patient .\nthe most common cause for intrapulmonary bleedings is the hemoptysis , due to bronchial artery erosion seen in as many as 95% of all cases . in contrast , bleeding from the pulmonary arteries is very rare , usually massive , accounting for less than 5% of all cases ( 5 ) , and is usually due to pseudoaneurysm rupture . because of the risk of pap enlargement and rupture , which leads to death in approximately 50% of patients , prompt therapy is required .\nthe available treatment modalities for pap are medical therapy , surgery and percutaneous catheter embolisation of the pseudoaneurysm .\nmedical treatment by the means of immunosuppressive drugs and steroids has been found to cure or decrease the size of aneurysms in behcets disease ( 6 , 7 ) .\nseveral surgical techniques , such as lobectomy , pneumonectomy , hilar clamping with direct arterial repair and ligation , have been used . however ,\nin our case , due to the patient 's severe pulmonary insufficiency , she was not a surgical candidate .\nthere are number of reports in the literature addressing the treatment of paps - most of them using metallic coils ( 8) or silicon balloon ( 9 ) to occlude the arterial feeders .\nthese placements can also occlude the perfusion to aerated lung , distal to the embolisation site , and are associated with complications , like coil migration and damage to vessel wall .\nother authors have occluded the pap by intraneurysmal placement of coils ( 10 ) ; however it carries a potential risk of mass effect and aneurysm rupture .\nstill , other authors have described the use of covered stents ( 11 ) , and recently , hovis and zeni ( 12 ) have used thrombin percutaneously for the paa refractory to coil the embolisation . in our case , initially , we attempted unsuccessfully to occlude the feeding artery with the coils .\nhowever , the coils migrated proximally to enter into the lower lobe circulation without compromising the blood circulation to these segments .\nwe later realized that this was due to a short length and wide neck of the feeding artery , that we were not able to keep the catheter stable in this branch .\nwe did not want to occlude the aneurysmal sac with coils , firstly because of the large size of the lesion , use of multiple coils could result in a mass effect after embolisation , and secondly it would have been very expensive ; also it might be further complicated by coil migration , resulting from the wide neck of the aneurysm . in our case , because of regular and comfortable experience at tackling abdominal visceral aneurysms with glue embolization , we decided to use this liquid material as embolic material .\n( 7 ) embolised the feeding branch to paa , using the glue with a \" bubble technique \" ; however , this was not possible in our case because of the short length in the feeding artery .\ntherefore , we considered the alternative option of intraaneurysmal injection of liquid embolic ( glue ) .\nglue ( n - butyl 2-cyanoacrylate ) is a rapidly hardening liquid adhesive , and has been used as an effective embolic agent for brain vascular malformations ; however , necessity of operator experience with the use of liquid embolic material is a major limitation in its application to aneurysms .\nthere are some studies showing the feasibility of intraaneurysmal injection of the glue in intracranial aneurysms ( 13 ) , thereby keeping the antegrade flow in the aneurysm bearing artery patent .\nwe report the first case , in which the n - butyl 2-cyanoacrylate was successfully injected , intraaneurysmally , through the transcatheter route for the occlusion of a pulmonary artery pseudoaneurysm , after an upper lobe lobectomy for aspergillosis .\nglue offers the advantage of permanent occlusion of the vessel , and because of its low viscosity , it can be injected through a microcatheter into small and tortuous arteries .\nit is admixed with ethiodized oil in various ratios to achieve radiopacity and to adjust the polymerization time allowing for more controlled embolisation . the use of higher concentrations of glue results in quicker solidification ; however , on the contrary , the longer the polymerization time , the greater the risk of non - target embolisation because there is the possibility of embolic material being washed away before it solidifies . in our case\nwe initially used 75% glue to prevent the reflux into the parent artery ; however there was early polymerisation of the glue with the sac preventing an evenly distribution .\ntherefore , we had to dilute the glue to make it 50% concentration , and this time , there was complete filling of the aneurysm . in conclusion\nintraaneurysmal injection of the liquid embolic materials is feasible , safe , and effective trancatheter treatment option for pulmonary artery aneurysms and is possibly not associated with the risk of rupture seen with packing of aneurysms with coils .\nhowever , appropriate concentration of the glue , long term results , and etc . will require further experience to confirm its safety and efficacy in pulmonary circulation .", "answer": "we report a case of pseudoaneurysm of the anterior ascending branch of the left pulmonary artery , following a left upper lobectomy for pulmonary aspergillosis , for which we have done an endovascular treatment . \n this is the first case where complete pseudoaneurysm occlusion was accomplished after a transcatheter intra - aneurysmal n - butyl 2-cyanoacrylate ( glue ) injection .", "id": 382} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe global prevalence of diabetes mellitus has been remarkably increased during the last two decades and has reached from almost 30 million cases in 1985 to 285 million cases in 2010 ( 1 ) .\nthe prevalence of diabetes in iran was about 7.7% in 2005 ( 2 ) , and this amount reached 8.7% in 2007 ( 2 ) . \nobviously , many factors are required to meet the needs of the patients with diabetes .\nalthough , complete treatment of diabetes is a long way ahead , medical care and sociopsychological support have great effects on its acute and chronic outcomes ( 3 ) . in light of high prevalence of this disease , it has become the subject of significant research in different clinical areas . because of the increased prevalence of diabetes and its complex etiology ,\nadaptation mechanisms are needed to make a change in the concepts of diabetes management and the treatment programs that have been considered so far .\nthis change should be from the physical variables to sociopsychological factors which may be effective on the disease management and its outcomes ( 4 ) .\nin addition , the new treatment recommendations have specifically confirmed the importance of the integration of sociopsychological concepts with the usual care of patients with diabetes .\nthis new approach helps them achieve suitable control over their glucose level and leads to the person 's high compatibility ( 5 ) .\nmarital satisfaction is a situation in which husband and wife have a sense of happiness and are satisfied from each other most of the times .\nsatisfactory relationships between couples can be measured by mutual love , the amount of caring from each other , and understanding of each other ( 6 ) . according to winch ( as cited in olia ) , marital satisfaction is the adaptation between the individual 's present situation in marital relationships and his or her expected situation .\nmarital satisfaction does not appear from thin air and its development needs the effort of the couple .\nthe study results show that the outcome of marital satisfaction ( supporting each other ) can affect people s health ( 7 ) .\nfurthermore , a positive correlation has been found between marital conflict , anxiety , depression , and the low level of physical health ( 8) .\nliterature review in iran and other countries revealed that there has been no study about the relationship between marital satisfaction and compatibility with diabetes in patients with type 2 diabetes . despite benefiting from multiple therapeutic interventions like diets , regular exercise , weight control , chemotherapies , and epidemiologic investigations\nthe aim of the present study was to investigate the relationship between marital satisfactions with compatibility with type 2 diabetes .\nthis study method was descriptive - correlative . the sample consisted of patients ( 20 - 60 years old ) with diabetes who refereed to diabetes clinic in meybod , iran .\nthe patients with the following criteria were enrolled in the study : being 20 to 60 years old , having diagnosed their disease at least one year before the study , visiting one of the physicians in the diabetes clinic , and having medical case with the physician . \nthe people who had the following exclusion criteria were omitted from the study : having history of other physical diseases except the ones related to diabetes symptoms , and having mental retardation or other psychological disorders before diabetes diagnosis . according to the mentioned criteria , 160 patients from the clinic members ( 103 females and 57 males ) were randomly selected .\nthe sample size was determined based on random sample size formula of krejcie ( 9 ) which estimated to be 160 out of community of 280 patients . at first the list of the names of all people who were at that age range\nthey were called and those who had the criteria for entering into the study were chosen and invited for participating in the study . the questionnaires that were used in this study\nthey believed that this scale is related to the changes that happen during the individual 's life ( 10 ) .\nthis questionnaire included 47 questions rated in a 5-point scale from completely agree to completely disagree .\nthe validity of the instruments was also calculated by content validity method and its reliability was calculated by retest method ( 0.82 ) that was significant ( 11 ) .\nthe factors are family relationships , relationship with friends , dependency and independency conflicts , physical image , and the attitude toward the disease .\nthese factors show how diabetes affects the individual 's way of living and his or her compatibility .\nthose responses that show positive compatibility with diabetes were given the score of 1 and those which show negative compatibility were given 0 .\nthe reliability of this questionnaire with retest method on 15 patients with diabetes was found 0.73 after 5 weeks , and its content validity was confirmed by 3 psychologists and endocrinologists and psychiatric nursing .\nthey believed that this scale is related to the changes that happen during the individual 's life ( 10 ) .\nthis questionnaire included 47 questions rated in a 5-point scale from completely agree to completely disagree .\nthe validity of the instruments was also calculated by content validity method and its reliability was calculated by retest method ( 0.82 ) that was significant ( 11 ) .\nthe factors are family relationships , relationship with friends , dependency and independency conflicts , physical image , and the attitude toward the disease .\nthese factors show how diabetes affects the individual 's way of living and his or her compatibility .\nthose responses that show positive compatibility with diabetes were given the score of 1 and those which show negative compatibility were given 0 .\nthe reliability of this questionnaire with retest method on 15 patients with diabetes was found 0.73 after 5 weeks , and its content validity was confirmed by 3 psychologists and endocrinologists and psychiatric nursing .\nmost of the study samples were in the age range of 41 - 50 with the frequency of 50 which involves 31.2% of the participants and the least frequency was in the age range of 21 - 30 with 11 ( 6.8% ) participants . also , most of the participants were women 103 ( 64.4% ) .\ntable 1 shows the mean and standard deviation of marital satisfaction and the aspects of compatibility with diabetes in the sample group .\ntable 1 shows that the mean and standard deviation of marital satisfaction in the sample group are respectively 136.9 and 14.07 , and the mean and standard deviation of compatibility with diabetes are respectively 40.12 and 3.33 . \ntable 2 shows the result of anova ( analysis of variance ) on the mean of marital satisfaction score in two groups ( men and women with diabetes ) .\ntable 2 shows that , there is no significant difference between women and men with diabetes regarding marital satisfaction ( p = 0.3 ) .\ntable 3 shows the correlation between marital satisfaction and aspects of compatibility with diabetes in women and men with diabetes .\ntable 3 shows that a positive , significant relationship exists between marital satisfaction and compatibility with diabetes in women ( p = 0.006 ; r = 0.26 ) .\nit means that as marital satisfaction increases in women with diabetes , compatibility with diabetes will also increase .\nhowever , there is no significant relationship between marital satisfaction and compatibility with diabetes in men with diabetes ( p = 0.87 ; r = 0.02 ) .\nalso , there is no significant relationship between aspects of compatibility with diabetes and marital satisfaction in women and men .\nas it was mentioned , the present study was carried out to investigate the relationship between marital satisfaction and compatibility with diabetes in patients with type 2 diabetes .\nthe results revealed that a positive significant relationship exists between marital satisfaction and compatibility with diabetes in women .\nit means that by increasing marital satisfaction , compatibility with diabetes increases and vice versa .\nin fact , marital satisfaction affects people 's mental health and these result are in consistent with the results of other studies ( 12 , 13 ) in which the relationship between mental health and marital satisfaction were investigated in people with chronic diseases .\nthe results of the other studies ( 14 , 15 ) in which the relationship between family support and blood glucose control was investigated in elderly with type 2 diabetes revealed that family support increases marital satisfaction which is in line with increasing the elderly mental health .\nelder and george ( 16 ) also cited in their study that close relationships are the main source of pleasure and support during life .\npeople who have closer relationships are in better physical and mental health condition ( 16 , 17 ) which is consistent with the results of this study .\nlal and bartle - haring ( 18 ) investigated marital satisfaction in patients with chronic lung diseases and their results also revealed that marital satisfaction was related to psychological improvement which could affect and alleviate their chronic pains .\nwhitsitt ( 19 ) investigated coping strategies and compatibility with coronary artery diseases in couples and the results showed that marital quality can affect better compatibility with the disease .\n20 ) revealed in their studies that the relationship between the couples can reinforce the behaviors related to health and lead to people 's improvement .\ntherefore , this issue destroys the balance of suitable behaviors and leads to loss of intimacy .\nmarital satisfaction is considered as a continuum and an evolutionary process between husband and wife .\nmarital satisfaction includes some elements such as self - esteem , self - effectiveness , domination , and control over life .\nthe weakness in any of these factors leads to the reduction in individual 's health and ability for dealing with his or her present conditions .\nin fact , marital satisfaction acts as a protective and reinforcing factor for the patient .\nwhen marital satisfaction is high , domination , control , and life expectancy will increase in the person and he or she tries more to improve himself or herself .\nwhen marital satisfaction is high , the person also benefits from the advantages of this relationship which occurs in a substitutive way and he or she can adopt his or her condition . in this study the interaction of variables like occupation , education , duration of marriage , number of children , personality , place of living , and other effective social and cultural variables were not examined with the test variables .\ntherefore , it is suggested that the relationship of test variables with other variables such as age , gender , education , duration of marriage , and personality be investigated in different cities .\nin addition , this study has its own limitations like the small number of the subjects who were a group of patients referred to the hospitals in meybod .\nso , further studies should be done , in different cities and on other age groups with other instruments and the results should be compared . in the future studies it is important to consider other psychological factors too , since investigating possible interactive effects of some personal issues in predicting compatibility with type 2 diabetes can help us in explaining problems regarding diabetes management in a more suitable way .", "answer": "background : marriage is a legal pact between a man and a woman for participating in a social life together which can play an important role in dealing with difficulties.objectives:this study was carried out to investigate the relationship between marital satisfaction and compatibility with diabetes in patients with type 2 diabetes.patients and methods : the study method was descriptive - correctional . \n the study sample included 160 diabetic patients ( 103 females and 57 males ) who were randomly selected . \n the instruments used were enrich marital satisfaction questionnaire and the questionnaire of compatibility with diabetes . \n in addition , the data were analyzed through descriptive statistics and analysis of variance by spss.results:the result of the study revealed a significant correlation ( p = 0.006 ) between marital satisfaction and compatibility with diabetes in women with type 2 diabetes ( r = 0.26 ) . \n however , this correlation was not significant in men with diabetes . also , a significant relationship existed between the dimensions of compatibility with diabetes and marital satisfaction in both men and women with diabetes.conclusions:marital satisfaction affects compatibility with diabetes in women . \n therefore , it might be possible to increase compatibility with diabetes in them by offering specialized interventions as family and couples therapies and giving consultations .", "id": 383} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nautoimmune polyglandular syndrome ( aps ) is a rare genetic disease that causes multiple endocrine disorders .\nthe vague presentation of endocrine dysfunction can cause a delay in both the diagnosis and the treatment of life - threatening conditions .\nwe , herein , present a case of aps in a 21-year - old man whose condition did not respond to initial treatment and in whom a definitive diagnosis was subsequently achieved by workup for hypocortisolism .\na 21-year - old man with a history of hashimoto 's thyroiditis with hypothyroidism presented to the emergency department for evaluation of an altered mental status .\nhe was very lethargic , stared blankly , and was unable to respond appropriately to questions .\nhe reported no fever , difficulty swallowing , shortness of breath , muscle or joint pain , headache , vomiting , or excessive thirst or urination .\nphysical examination revealed a temperature ( t ) 34.3c , heart rate ( hr ) 68/min , respiratory rate ( rr ) 16/min , and blood pressure ( bp ) 87/57 mmhg .\nhe was very lethargic , confused , and able to answer only yes - or - no questions .\nthe patient exhibited hyponatremia ( 128 meq / l ) , hypoglycemia ( 29 mg / dl ) , and a high thyroid - stimulating hormone ( tsh ) level ( 14.31 iu / ml ) .\ntest for other metabolic panel , complete blood count , triiodothyronine and thyroxine levels , head computed tomography , and urine toxicology screening results were all normal .\nhe was diagnosed with severe hypothyroidism and received 2 l of fluid for resuscitation , 25 g of dextrose , and a single intravenous ( iv ) dose of 100 mcg levothyroxine at the emergency department .\na random serum cortisol level was < 1.0 g / dl . a 250 g adrenocorticotropic hormone ( atch ) stimulation test was < 0.1 g / dl . he was diagnosed with primary adrenal insufficiency and received a treatment with iv hydrocortisone .\nhis mental status , generalized fatigue , and metabolic parameters including glucose and sodium levels substantially improved .\naps type 2 ( aps2 ) was suspected based on his history of hypothyroidism and primary adrenal insufficiency .\nthe results of an additional liver function test , anti - gad65 antibody titer , testosterone level , and plasma renin activity were all within normal limits .\nthe patient had returned to his normal level of activity by the time of the outpatient follow - up and reported feeling much better after treatment with hydrocortisone , fludrocortisone , and levothyroxine .\nthe present case illustrates an example of aps2 , the clinical presentation of which may overlap that of primary adrenal insufficiency and hypothyroidism due to autoimmune thyroiditis .\nthe present patient exhibited lethargy , an altered mental status , hypothermia , hypotension , hypoglycemia , an elevated tsh level , and normal thyroxine levels .\nhe was later found to have primary adrenal insufficiency and his clinical symptoms improved after receiving corticosteroid replacement therapy .\nother autoimmune diseases , especially of the skin , stomach , and gonads , may occur with increased frequency in patients with aps2 .\nthe greatest danger associated with aps2 is treatment of the presenting hypothyroid state without recognition of concomitant hypoadrenalism .\nhypothyroidism reduces cortisol clearance , and the addition of thyroid hormone replacement increases cortisol clearance .\nadditionally , hypothyroidism reduces the metabolic rate , thereby , reducing the need for cortisol . the increased metabolic rate accompanying thyroxine replacement increases the requirement for cortisol .\nfurthermore , a high serum concentration of tsh in the absence of primary thyroid failure can be a feature of adrenal insufficiency .\nthe development of an adrenal crisis due to underlying adrenal insufficiency has been reported after the administration of thyroxine replacement therapy to patients initially thought to have only hypothyroidism .\nthe management of aps2 is based on individualized , lifelong replacement therapy for the affected endocrine organs plus monitoring for development of insufficiency in other organs or associated conditions .\nthe use of medical alert sensors and other measures should be taken to ensure that adrenal function is considered during illness , surgery , or emergency situations .\nin summary , we have reported a case involving a patient with aps2 who presented with lethargy , hypotension , hypoglycemia , and an elevated tsh level .\nthe vague presentation of this syndrome can cause missed or delayed treatment for adrenal insufficiency resulting in a life - threatening adrenal crisis .", "answer": "context : \n autoimmune polyglandular syndrome is a rare condition that causes a variety of clinical symptoms due to autoimmune processes involving multiple endocrine organs . its vague presentation can cause missed or delayed treatment for adrenal insufficiency , resulting in a life - threatening adrenal crisis.case report : a 21-yr - old man presented with lethargy , hypotension , hyponatremia , hypoglycemia , and an elevated thyroid - stimulating hormone level . \n he was binge drinking the day before presentation . \n no significant response to initial treatment with levothyroxine and dextrose occurred . \n diagnostic workup later revealed primary adrenal insufficiency . \n all initial symptoms completely resolved following treatment with hydrocortisone , fludrocortisone , and levothyroxine.conclusion:autoimmune polyglandular syndrome causes dysfunction of multiple endocrine organs such as the thyroid gland , adrenal gland , and pancreas . initial diagnosis of aps is crucial and difficult because of its vague , acute presentation , which often involves hypothyroidism and adrenal insufficiency . \n delayed treatment of adrenal insufficiency can result in a life - threatening adrenal crisis . a diagnostic workup for adrenal insufficiency \n should be performed in patients who do not respond to hypothyroidism treatment .", "id": 384} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na study on serologic and molecular characterization of denv isolates was initiated in january 2005 at the fundao de medicina tropical do amazonas ( fmtam ) .\nparasite - negative patients who had clinical symptoms of malaria were invited to participate in the study .\neach patient received essential information and signed a consent form approved by the fmtam ethical committee .\nall serum samples were collected during the acute phase of illness and tested for denv infection by using 3 methods .\nthe first method was virus culture , for which serum samples were placed on the aedes albopictus cell line c6/36 grown in leibovitz-15 medium containing 5% fetal bovine serum , followed by viral antigen identification with type - specific monoclonal antibodies in an indirect immunofluorescence assay ( 8) . the second method was detection of immunoglobulin m antibodies to denv by an elisa on serum samples from patients > 7 days after onset of symptoms ( 9 ) .\npcr ( rt - pcr ) protocol on the basis of that described by lanciotti et al .\nbriefly , viral rna was extracted by using the qiaamp viral rna mini kit ( qiagen , valencia , ca , usa ) , and reverse transcription was conducted on 5 l of extracted rna with superscript iii ( invitrogen , carlsbad , ca , usa ) and random primers .\nafter incubation for 1 h at 50c , 2 l of each cdna was subjected to pcr amplification with d1 and d2 primers for 35 cycles consisting of 1 min at 94c , 1 min at 55c , and 1 min at 72c , and a final extension for 10 min at 72c .\na second round of amplification was conducted with 10 l ( diluted 1:100 ) of the first amplicon , a mixture of type - specific reverse primers ( ts1ts4 ) , and the conserved forward primer d1 .\ndenv-4 was detected in 3 samples ( am750 , am1041 , and am1619 ) by virus culture or rt - pcr .\nit was identified as a co - infecting virus with denv-3 in isolate am750 ; samples am1041 and am1619 represented single denv-4 infections ( table ) . to confirm these results ,\ngenerated amplicons were cloned into a ta vector ( invitrogen ) , and > 3 colonies for each sample were sequenced in both directions by using the bigdye terminator cycle sequence kit ( applied biosystems , foster city , ca , usa ) .\ndenv-3 and denv-4 nucleotide sequences obtained were subjected to a basic local alignment search tool ( blast ) ( www.ncbi.nlm.nih.gov/ ) analysis that used the megablast algorithm optimized for highly similar sequences . using this approach , we obtained sequences with identities ranging from 95% to 99% for denv-3 and 94% to 98% for denv-4 for isolates am750-d3 , am750-d4 , and am1619 .\neu127898 ( am750-d3 ) , eu127899 ( am750-d4 ) , and eu127900 ( am1619 ) .\n* igm , immunoglobulin m ; m - pcr , multiplex typing pcr described by lanciotti et al .\n( 10 ) ; s - pcr , single serotype - specific primer pcr ; d , dengue serotype ; blast , basic local alignment search tool ; ns , not sequenced . \nisolate am750 is from a person with a co - infection ; different clones were sequenced .\nthe 3 denv-4positive samples were obtained from patients who lived and worked in manaus and reported no travel history for > 15 days before onset of symptoms .\nthese samples were obtained during another study that identified 62 denv - positive samples from january 2005 through june 2007 ( 24 denv-2 , 35 denv-3 , and the 3 denv-4 cases in our study ) among 128 samples tested from patients in 14 municipalities in amazonas .\nsince its introduction into the western hemisphere in 1981 , denv-4 has been associated with dengue fever and only sporadically associated with serious cases of dhf or dss ( 1 ) .\na study in colombia found more dhf patients infected with denv-2 than with denv-3 or denv-4 ( 11 ) .\nconversely , another study showed an association of denv-4 with an epidemic of dhf that occurred in mexico in 1984 ( 12 ) .\nthere are many host ( and perhaps viral ) factors in dengue infections that may lead to development of dhf . on the basis of the antibody - dependent enhancement hypothesis\n, the most important factors would be those generated by the patient s immune response upon secondary infections ( 13 ) .\nthe 3 isolates reported in our study were from patients with no travel history , which indicates that denv-4 is present in manaus .\ndetection of denv-4 in brazil co - circulating with other denv serotypes endemic to this country represents an increased risk for dhf or dss because many persons have been sensitized by previous dengue infections but are not protected against infection with denv-4 .\nthe first report of denv-4 in brazil was in the state of roraima in 1982 .\nsince that time , no other isolate of denv-4 has been reported in any part of brazil ( 14,15 ) .\nthe resurgence of denv-4 in the amazon region of brazil most likely resulted from the proximity of brazil to denv-4endemic countries ( venezuela and colombia ) .\nadditional genotyping studies are being conducted to verify this assumption and to obtain information on dengue epidemiology in brazil .\nour study documents the detection of denv-4 in manaus , amazonas , and the first isolation of this serotype in brazil in 25 years .\nthese findings reinforce the need for continual epidemiologic studies and use of classic and molecular approaches in the surveillance of emerging or reemerging diseases .", "answer": "we report dengue virus type 4 ( denv-4 ) in amazonas , brazil . \n this virus was isolated from serum samples of 3 patients treated at a tropical medicine reference center in manaus . \n all 3 cases were confirmed by serologic and molecular tests ; 1 patient was co - infected with denv-3 and denv-4 .", "id": 385} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSelective Recognition of d-Aldohexoses in Water by Boronic Acid-Functionalized Molecularly Imprinted Cross-Linked Micelles\n\nPaper sections:\n\nCarbohydrates are one of the most important classes of biomolecules and involved in numerous biological processes including cell\u2013cell interaction, immune response, and viral and bacterial infection.1,2 Synthetic analogues of carbohydrate-binding lectins are powerful tools for the detection of biologically important sugars and intervention of carbohydrate-mediated interactions.3 Although receptors based on both covalent4-8 and noncovalent9-12 interactions have been reported, a general method for selectively binding carbohydrates in water remains elusive.13,14
As building blocks of oligo- and polysaccharides, the eight d-aldohexoses differ only in the stereochemistry of 1\u20133 hydroxyls. Unfortunately, the hydroxyl group is not a good functional group handle from the supramolecular viewpoint, because its strong solvation by water makes it difficult to use hydrogen bonds to bind a sugar. Having the same number of carbon and hydroxyls, the aldohexoses have only minute differences in hydrophobicity, mainly in the axial/equatorial distribution of the hydroxyls. Although the difference has been used successfully to distinguish glucose/glucoside from other monosaccharides,11,15 it is not clear how the other d-aldohexoses can be differentiated in this regard.
Despite these tremendous challenges, literature suggests boronic acid-based covalent receptors could potentially overcome the difficulty. Boronic acid-functionalized molecularly imprinted polymers (MIPs) were reported in the 1970s by Wulff as the stationary phase to separate sugar derivatives by chromatography.16 Monoboronic acids generally bind fructose more strongly than glucose due to its higher percentage of furanose that contains the preferred synperiplanar 1,2-diol for boronate formation.17 This selectivity, interestingly, could be reversed with diboronic acids preorganized to form boronate with the particular hydroxyls of glucose, whether the furanose or pyranose form.18-21 The preorganization comes from the organic scaffold whose structure and conformation dictate how the diboronic acids interact with its guests. Strongest binding is obtained when the maximum number of boronate ester bonds are formed with minimal strain.
The above results suggest that a general method to recognize carbohydrates might result if the number, distance, and orientation of boronic acids on the receptor can be tuned precisely to match the hydroxyl groups on the guest. Such structural control, however, is difficult to imagine given the minute structural differences of the carbohydrates.
Herein, we report that this level of structural precision can be readily obtained through covalent molecular imprinting within cross-linked micelles. The molecularly imprinted nanoparticles (MINPs) obtained practically could distinguish all eight d-aldohexoses based on the configurations of the hydroxyls. This work lays the foundation for the construction of receptors to bind more complex carbohydrates, since different hydroxyls contributed quite differently to the binding.
With a tripropargylammonium headgroup, surfactant 1 could be cross-linked in the micellar form on the surface by click chemistry with diazide 2 (Scheme 1), to afford alkynyl-functionalized surface-cross-linked micelles (i.e., alkynyl-SCM).22-24 Template 3 was solubilized in water together with DVB and a photoinitiator (DMPA) by 1 in the very beginning. It was prepared from 4-vinylphenylboroxine and glucose according a literature procedure.25 Because the diboronate product contains different isomers (e.g., 3a, 3b, etc.) that undergo transesterification during repeated crystallization, the material obtained from a single crystallization was used without further purification.26 After surface-cross-linking, azide 3 was added to decorate the resulting alkynyl-SCMs with a layer of hydrophilic ligands. Free radical polymerization was subsequently initiated by UV irradiation in the core to polymerize/cross-link the methacrylate of 1, DVB, and the polymerizible styrenyl groups of 3. The doubly cross-linked micelles were recovered by precipitation from acetone. Glucose was removed by repeated washing with acetone/water, methanol/acetic acid, and acetone.27 Template 3 has a free hydroxyl. As demonstrated previously, hydrophilic groups on the template anchor the template near the surface of the micelle/MINP and is helpful to its removal/rebinding.28,29
The MINP preparation was adapted from our published procedures.28-31 Cross-linking of the micelles and formation of the MINPs likewise were monitored by 1H NMR spectroscopy and dynamic light scattering (DLS), as shown by Figures S1 and S2 in the Supporting Information. DLS also allowed us to estimate the molecular weight of the nanoparticles. SCMs were characterized previously also by transmission electron microscopy (TEM) and mass spectrometry (after cleaving the surface-cross-linkages).22
To understand the potential of MINPs in carbohydrate recognition, we prepared boronic acid-functionalized receptors first for glucose, mannose, and galactose. Among the eight d-aldohexoses, these three are most biologically relevant, serving as building blocks for many naturally occurring oligo- and polysaccharides. We also prepared MINP(5), using the diboronate derivative of 4-nitrophenyl \u03b1-d-mannopyranoside 5 as the template. We are interested in the glycoside because the added hydrophobic aglycan potentially could contribute to the binding. In addition, the glycoside will be bound in the pyranoside form, different from the free sugars.
All the bindings were studied by isothermal titration calorimetry (ITC). The method previously was found to yield similar binding constants (Ka) as fluorescence titration for fluorescently labelled templates.28-31 As shown in Table 1, Ka between MINP(glucose) and glucose was 1.18 \u00d7 103 M\u22121 in 10 mM HEPES buffer at pH 7.4. This binding affinity compares favorably with those between lectins and their monosaccharide ligands (typically 103\u2013104 M\u22121).1,2 Importantly, the MINP receptor displayed excellent selectivity, showing negligible binding toward other d-aldohexoses except allose (Ka = 0.52 \u00d7 103 M\u22121). Binding with selected non-aldohexoses was very weak, with Ka = 0.06 and 0.003 \u00d7 103 M\u22121 for fructose and xylose, respectively. Thus, covalent imprinting within the cross-linked micelles must have positioned the boronic acids quite accurately to match the hydroxyls on the templating sugar. Our MINPs were prepared with a 1:1 surfactant/DVB ratio. This amount of DVB was the maximum that could be solubilized by the micelle and corresponds to ~50 molecules of DVB per micelle. The high cross-linking density was found previously to be critical to the MINP binding selectivity.28
To our delight, the binding selectivity was reproduced when mannose and galactose were used as the templates. MINP(mannose), for example, bound its sugar template with Ka of 0.94 \u00d7 103 M\u22121 and no other d-aldohexoses except altrose (Ka = 0.56 \u00d7 103 M\u22121) (Table 1, entries 13\u201320; see Chart 1 for structures). MINP(galactose), likewise, only bound its template (Ka = 1.41 \u00d7 103 M\u22121) and one other sugar (gulose, Ka = 0.80 \u00d7 103 M\u22121) among the d-aldohexoses (Table 1S).
Molecular imprinting has become a very powerful technique to create guest-complimentary materials.32-43 Conventional typical MIPs, however, are intractable highly cross-linked polymers. In our case, because polymerization and cross-linking largely occurred within the boundary of the micelles, the MINPs were completely soluble in water due to their nanosize and hydrophobic/hydrophilic core\u2013shell structure.28-31 Note that most MINPs in Table 1 had a single binding site per nanoparticle on average.44 The number of binding site per nanoparticle is controlled by the surfactant/template ratio used in the MINP preparation and, as demonstrated earlier, is fully tunable if desired.28 This number was determined by the ITC titration from the guest/host ratio.45 Previously, the ITC-determined binding stoichiometry was found to agree well with those determined by the Job plots for fluorescently labeled substrates.46
It is very interesting that a consistent binding selectivity was displayed by all three MINPs. Strong binding for the template sugar was fully expected. Why did the MINP bind only one of the remaining d-aldohexoses? The answer becomes clear when the following trends are considered.
(a) Inversion of two (or more) hydroxyl groups of the templating sugar turns off the binding essentially completely. This trend was seen from glucose to any of the diaxial sugars, and from mannose to allose/galactose/idose. The anomeric hydroxyl at C1 was not considered because it exchanges between the \u03b1 and \u03b2 form as the hemiacetal.
(b) The effect of a single hydroxyl inversion depends on the position of the hydroxyl. Consistently for all three MINPs, inversion at either C2 or C4 turned off the binding\u2014e.g., from glucose to mannose/galactose or from mannose to glucose/talose. Inversion at C3, however, weakened the binding by 40\u201360%, e.g., from glucose to allose, mannose to altrose, or galactose to gulose. As shown by xylose, missing the C6 hydroxyl also caused a complete loss of binding.
When monoboronic acids bind free monosaccharides, literature generally agrees that binding of the first boronic acid occurs through the C1,2 hydroxyls of the sugar.4,47,48 Binding of the second boronic acid, however, could differ depending on the reaction conditions (e.g., aqueous or nonaqueous solvent, solution pH, concentration) and the structure of the boronic acid. The situation is complicated further by pyranose\u2013furanose interconversion. Furanose, having the preferred synperiplanar 1,2-diols for boronate formation,17 is generally the minor component, sometimes representing <1% of the mixture. Nonetheless, two or all three of the C3,5,6 hydroxyls are frequently involved in the second boronate formation for furanose.4 There is also evidence that, for certain sugars, additional conformations (e.g., twist boat) may play roles in the binding, at least in aqueous alkaline media.48
In our case, the hydroxyls at C2, C4, and C6 were critical to the binding and the C3 hydroxyl played a secondary role. The results suggest that, under our conditions, the boronic acids probably bound two pairs of hydroxyls, at C1,2 and C4,6, respectively. Because the boronate template was synthesized in organic solvent under azeotropic distillation, neutral trivalent boronate esters instead of negatively charged tetravalent structures are expected.4
Solution pH has a large effect on the binding of small-molecule boronic acids. A change of pH from 6.5 to 8.5 increased the binding constant between phenyl boronic acid and glucose by over an order of magnitude.49 The pH effect came from the acid\u2013based equilibria involved in the binding and the tetrahedral vs. trigonal forms of boronic acid/boronate. In our case, the same pH change barely had any effect on the MINP binding (compare entries 1, 11, and 12 of Table 1). Presumably, the overall hydrophobicity of the diboronate template means that the boronic acids would reside in a relatively hydrophobic region of the MINP. With poor solvent exposure, neither the boronic acids nor the boronate esters formed after binding would be very sensitive to the solution pH.
4-Nitrophenyl \u03b1-d-mannopyranoside 5 should interact with the MINP receptor through hydrophobic interactions, in addition to two boronate esters through the C2,3 and C5,6 hydroxyls.25 After template removal, a binding site is expected to form in the hydrophobic core of the cross-linked micelle, complementary to the 4-nitrophenyl group in size and shape. The hydrophobic imprinting worked very well for many substrates in our previous work.28-31 Consistent with the added hydrophobic interactions, binding between 5 and MINP(5) was over twenty times stronger than those between the sugars and their MINPs (Table 1, entry 21). Encouragingly, significant selectivity was found for the binding of similar glycosides. Glucopyranoside 6 was bound by MINP(5) with <1/3 of the binding affinity and mannopyranoside 7 with ~1/6. Apparently, inversion of one or two hydroxyl groups could still be easily distinguished, even for the pyranosides. Lastly, MINP(5) was also able to bind mannose with Ka = 0.5 \u00d7 103 M\u22121 (entry 24). The binding constant was similar to that between mannose and its own MINP (entry 14). Thus, the binding site imprinted from the mannopyranoside was able to bind mannose, most likely in the pyranose form.
The most significant discovery of this research is the general applicability of the MINP receptors, which are completely water-soluble and similar to proteins in size. It is very important that the MINP receptors displayed a very clear and consistent trend in the binding, mainly controlled by the C2, C4, and C6 hydroxyls of the d-aldohexoses. The milli- and submillimolar binding affinities already approached those found in natural lectins for monosaccharides. The observed binding selectivity suggests that the cross-linked micelles can be used as a platform to precisely position and orient binding groups even to distinguish minute structural changes in carbohydrates. If the same holds true for oligo- and polysaccharides, a general method for selective binding of carbohydrates will become available.
", "answer": "Molecular imprinting within cross-linked micelles using 4-vinylphenylboronate derivatives of carbohydrates provided water-soluble nanoparticle receptors selective for the carbohydrate templates. Complete differentiation of d-aldohexoses could be achieved by these receptors if a single inversion of hydroxyl occurred at C2 or C4 of the sugar or if two or more inversions took place. Glycosides with a hydrophobic aglycan displayed stronger binding due to increased hydrophobic interactions.", "id": 386} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbased on recent basic and clinical studies , it has been shown that adipocytokines may contribute to the induction of carcinogens and progression of tumors ( 1 ) . \n \n\nvisfatin was initially recognized as a growth factor for proliferation of b - cell lymphocyte , called the pre - b cell colony - enhancing factor .\nsubsequently , it was found as a cytokine present in a variety of cells and tissues with metabolic and inflammatory effect .\nvisfatin have also been shown to correlate with pro - inflammatory cytokines such as il-1 , il-6 , and tnf . it stimulates il-6 and il-8 and may be associated with oxidative stress parameters .\nmodulation of insulin by binding to the insulin receptor is another recognized function for visfatin ( 2,3 ) . \n \n\npreviously , we reported the levels of various adipocytokines in patients with colorectal cancer and we found a significant increase in the visfatin serum level in colorectal cancer patients comparing to controls ( 4 ) .\ntherefore , we examined if this cytokine increases in patients with colorectal adenoma as a precursor of colorectal cancer .\nto the best of our knowledge , in addition to a previous study done by nakajima et al .\n( 1 ) , the present study is among the first reports to evaluate the visfatin level in patients with colorectal adenoma comparing to healthy controls . \n\n\n this case - control study was conducted at the department of surgery of imam medical complex affiliated to tehran university of medical sciences . between january 2014 and june 2015\n, a total of 34 patients diagnosed with colorectal adenoma and 35 disease - free controls were included in case and control groups , respectively .\npatients with a previous history of any colorectal disease including polyps , adenoma , irritable bowel disease or cancerous lesion were excluded from the study .\ndisease - free controls were selected from participants in the persian gulf healthy heart study ( 5 ) .\nthis study was carried out between march 2013 and march 2015 in colorectal surgery department of tehran university of medical sciences .\nall the patients were informed about the study and written informed consent was taken from each patient . \n \n for each patient , systolic and\nbody mass index ( bmi ) and waist - to - hip ratio ( whr ) were calculated after measuring height , weight , waist circumference ( midway level between the costal margins and the iliac crests ) and hip circumference ( at the level of the greater trochanters ) . in order to measure serum markers ,\nfasting venous blood samples were obtained from all patients and the disease - free controls .\nserum biochemical parameters including blood glucose , triglyceride , and cholesterol levels were measured on the day of sampling using selectra 2 autoanalyzer ( vital scientific , spankeren , netherlands ) .\nserum cholesterol ( hdl and total ) and triglyceride levels were measured using cholesterol oxidase / phenol aminoantipyrine and glycerol-3-phosphate oxidase phenol aminoantipyrine enzymatic methods , respectively . in cases with triglycerides level of less than 400 mg / dl , serum ldl was calculated using the friedewald formula .\nenzyme - linked immunosorbent assay kits ( adipogen , seoul , korea ) were utilized in order to measure visfatin levels .\nthe assay sensitivity for visfatin was 0.10 ng / ml ; the intra- and inter - assay coefficients of variance were 3.85.5% and 6.49.5% , respectively . \n \n\ndescriptive values were expressed as the mean sd . in order to compare visfatin levels between groups a two - tailed t - test was considered .\npearson s correlation was also used to assess the relationship between visfatin levels and other measured variables .\n\n this case - control study was conducted at the department of surgery of imam medical complex affiliated to tehran university of medical sciences . between january 2014 and june 2015\n, a total of 34 patients diagnosed with colorectal adenoma and 35 disease - free controls were included in case and control groups , respectively .\npatients with a previous history of any colorectal disease including polyps , adenoma , irritable bowel disease or cancerous lesion were excluded from the study .\ndisease - free controls were selected from participants in the persian gulf healthy heart study ( 5 ) .\nthis study was carried out between march 2013 and march 2015 in colorectal surgery department of tehran university of medical sciences .\nall the patients were informed about the study and written informed consent was taken from each patient . \n \n for each patient , systolic and\nbody mass index ( bmi ) and waist - to - hip ratio ( whr ) were calculated after measuring height , weight , waist circumference ( midway level between the costal margins and the iliac crests ) and hip circumference ( at the level of the greater trochanters ) . in order to measure serum markers ,\nfasting venous blood samples were obtained from all patients and the disease - free controls .\nserum biochemical parameters including blood glucose , triglyceride , and cholesterol levels were measured on the day of sampling using selectra 2 autoanalyzer ( vital scientific , spankeren , netherlands ) .\nserum cholesterol ( hdl and total ) and triglyceride levels were measured using cholesterol oxidase / phenol aminoantipyrine and glycerol-3-phosphate oxidase phenol aminoantipyrine enzymatic methods , respectively . in cases with triglycerides level of less than 400 mg / dl , serum ldl was calculated using the friedewald formula .\nenzyme - linked immunosorbent assay kits ( adipogen , seoul , korea ) were utilized in order to measure visfatin levels .\nthe assay sensitivity for visfatin was 0.10 ng / ml ; the intra- and inter - assay coefficients of variance were 3.85.5% and 6.49.5% , respectively . \n\ndescriptive values were expressed as the mean sd . in order to compare visfatin levels between groups a two - tailed t - test was considered .\npearson s correlation was also used to assess the relationship between visfatin levels and other measured variables .\n\n in this study a total of 69 cases including 34 patients with colorectal adenoma and 35 disease - free controls were enrolled .\npatients included 18 males ( 53% ) and 16 females ( 47% ) and controls were 18 male ( 51% ) and 17 female ( 49% ) . patients and controls were also matched regarding their age as well .\ndemographic information of both groups and other studied variables including systolic and diastolic blood pressures , body mass index ( bmi ) , waist to hip ratio and lipid profile of patients have been summarized in table 1 . as can be seen in table 1\n, there was no significant statistical difference among the patients and the controls in terms of these variables ( p>0.05 in all comparisons ) . \n \n\n* p < 0.05 were considered significant . \n \n * * two - tailed t - test was used to compare visfatin levels between groups .\npearson s correlation was used to evaluate the relationship between visfatin levels and other measured variables . \n \n\nmeansd of visfatin levels in male and female patients were 6.33.01ng / ml and 7.13.05ng / ml , respectively . the visfatin level in the control group was 7.22.41ng / ml and 6.42.59ng / ml for males and females , respectively\n. moreover , there was no significant difference in terms of the visfatin level between both gender in each group ( p=0.482 for patients and p=0.375 for controls ) .\nwe also tried to analyze any possible correlation between the visfatin levels and each of the mentioned studied variables . except for a significant correlation between the bmi value and visfatin level ( p=0.041 ) ,\nvisfatin levels were analyzed separately based on the location of the adenoma within the large intestine in the patient group ( table 2 ) .\nwe found no significant difference between the levels of visfatin in each location comparing the healthy controls ( p>0.05 in all comparisons ) .\nthere was no statistical difference between the locations groups in terms of visfatin level as well ( p=0.068 ) . \n \n\n* values show possible differences between visfatin levels of patients suffering from adenoma in each part of colon or rectum comparing to the control levels . \n\n\n visfatin can be found in significant amounts in adipose tissue and it is produced primarily by visceral adipose tissue .\ntherefore , visfatin serum levels may be affected by a change in body weight and relationship between obesity , bmi and serum levels of visfatin has also been documented ( 2,6 ) .\nalthough the visfatin level had a significant relation with the bmi value in our adenoma patients , we found no statistical significant relation in the healthy controls . \n \n\nmetabolic syndrome is a group of harmful metabolic abnormalities , including visceral obesity , hyperglycemia , dyslipidemia , and hypertension .\nincreased circulating visfatin levels have also been found in patients with metabolic syndrome ( 7,8 ) .\ntherefore , we tried to depict any relation between visfatin level and metabolic abnormalities involved in metabolic syndrome in patients with colorectal adenoma .\nalthough we found a significant relation between the visfatin level and bmi of patients , we did not detect any relation for hyperglycemia , hypertension ( systolic and diastolic ) and dyslipidemia ( hyper cholesterolemia or hypertriglyceridemia ) . \n \n\nsigmoid ( 13 patients , 38.2% ) and rectum ( 13 patients , 38.2% ) were the most common site followed by ascending colon ( 6 patients , 17.6% ) . ascending ( 3.923.25 ng / ml ) and transverse colon ( 8.551.34 ng / ml ) had the lowest and highest mean serum levels of visfatin , respectively .\nnevertheless , our analysis revealed no significant difference between these levels and the value for the visfatin level in normal controls .\nnakajima et al . ( 1 ) analyzed the possible relations between the size and number of colorectal adenomas and some adipocytokines including the visfatin .\nthey found that except for adiponection , other cytokines including the visfatin has no relation with these two factors .\nconsequently , according to this study and our findings , it seems that size , number and location of colorectal adenoma are not influential factors affects the adipocytokine levels . \n \n\nlow number of cases was the major limitation in our study . designing another study with higher number of patients\n\n although visfatin level has been shown to be increased in serums of patients with colorectal cancer , it does not significantly increase in cases with colorectal adenoma .\nsite of adenoma within the colon or rectum does not seem to play an important role in this regard as well .", "answer": "background : visfatin is an adipocytokine secreted by visceral adipose tissue . it has been shown \n that adipocytokines may contribute to the induction of carcinogens and progression of tumors . previously , \n we found a significant increase in the visfatin serum level in colorectal cancer patients . \n herein , \n we investigated if this cytokine increases in patients with colorectal adenoma as a precursor of \n colorectal cancer . \n\n \n methods : in this case - control analytic study , a total of 34 patients diagnosed with colorectal adenoma \n and 35 disease - free controls were included . \n adenomas were also categorized based on their \n location within the colon . \n visfatin serum levels were measured in all cases and controls using enzyme- \n linked immunosorbent assay kits . in order to compare visfatin levels between groups a twotailed \n t - test was considered . \n pearson correlation was also used to assess the relationship between \n visfatin levels and other measured variables . \n\n \n results : patients included 18 male ( 53% ) and 16 female ( 47% ) with a meansd age of 48.310.96 \n years and controls were 18 male ( 51% ) and 17 female ( 49% ) with a meansd age of 51.612.52 \n years . there were no significant difference in terms of the visfatin level between the two groups \n ( 6.73.01 ng / ml for patients and 6.82.49 ng / ml for controls , p>0.05 ) . except for a significant correlation \n between the bmi and visfatin level ( p=0.041 ) , no other correlation was detected . \n we found no \n significant difference between the levels of visfatin in each location of adenoma comparing the \n healthy controls ( p>0.05 in all comparisons ) . \n there was no statistical difference between the locations \n groups in terms of visfatin level as well ( p>0.05 ) . \n\n \n conclusion : visfatin serum level does not significantly increase in patients with colorectal adenoma . \n site of adenoma within the colon or rectum does not seem to play an important role in this regard \n as well .", "id": 387} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan 81-year - old female with oavs presented to a general dentist for a dental implant consultation .\nher medical history was remarkable for an epibulbar dermoid and previous grafting of an anterior mandibular defect at the age of 16 .\nafter a routine examination , the patient was referred to an oral and maxillofacial surgeon for implant treatment planning .\nthe surgeon requested a maxillofacial cbct scan extending from the level of the nasal fossa through the inferior border of the mandible , and from the anterior border of one ramus to the anterior border of the contralateral ramus . upon radiographic examination ,\nthe bilateral paramedian area of the mandible appeared abnormally heterogeneous with a poorly defined border on the right .\nthe mandibular canals anterior to the right second molar and the left mental foramen were untraceable ( fig .\n1 ) . multiplanar reconstructions revealed a large , heterogeneous , expansile entity of mixed density along the facial side of the mandible , extending from the mandibular left premolar area to the mesial aspect of the mandibular right third molar , and from the level of the root apices through the inferior border of the mandible .\neffacement of the facial cortical plate without an effect on the neighboring teeth was observed ( fig .\n3 ) . three - dimensional volume rendering depicted the considerable size of the entity in question ( fig .\n4 ) . a cartilaginous neoplasm could not be ruled out based on cbct imaging and an incisional osseous biopsy was therefore performed .\nhematoxylin and eosin - stained slides prepared after formalin fixation and decalcification were reviewed ( fig .\ngrowth or overgrowth is a recognized sequela of ccgs . almost all patients that seek corrective surgery following ccg overgrowth in the mandibular body or condyle present with facial asymmetry .\nthis happens even when the grafts are placed bilaterally due to their unpredictable growth potential . for a definitive diagnosis to be made , radiographic examination followed by a histopathological evaluation is indicated.9 most of the published cases of ccg overgrowth in the mandible were described radiographically using panoramic images and/or multi - detector computed tomography ( mdct).10111415161718 yang et al.9 reviewed 68 cases of ccg overgrowth in the maxillofacial region .\nthe authors described a case of overgrowth of a ccg that replaced the right mandibular body using panoramic , lateral cephalometric , and posteroanterior skull radiographs , and mdct .\nnone of the radiographs demonstrated asymmetry due to the inherent limitations of this imaging modality .\nmdct allowed better visualization of the facial deformity and chin deviation in all dimensions.9 the advantage of the 3-dimensional visualization of such complex cases using mdct is indisputable .\nhowever , plain radiography is still commonly used due to its availability , low cost , and reduced patient exposure to ionizing radiation .\nthe authors reported 4 cases that demonstrated low - attenuation grafts with occasional foci of high attenuation , clear borders between the graft and host bone , and lateral and superior rims of ossification using mdct .\nthe follow - up period of these cases ranged from 5 months to 8 years .\na clear border was only seen in the case in which only 5 months had elapsed since surgery .\nfukuta et al.16 published a case of recurrent overgrowth of a ccg placed for hemimandibular reconstruction using panoramic images , mdct , and a nuclear medicine bone scan .\nthese images were of poor quality , but the authors noted the deviation of the mandible on mdct on 2 occasions ( before each corrective operation ) and increased uptake of the radionuclide by the graft on the third day after surgery .\nthis profound growth potential may have been due to the patient 's young age ( 2 years old ) .\nsimilarly , samman et al.18 demonstrated an increase in isotope uptake by the graft using technetium scintigraphy , supporting the theory that ccgs have an inherent growth potential .\nkaban et al.11 described the incorporation and calcification of a ccg replacing the mandibular condyle , and ultimately resembling a normal condyle upon periodic follow - up .\nunfortunately , the quality of the images was poor in the previous articles , which made us unable to evaluate the imaging findings .\neckardt et al.10 described a case of ccg reconstruction after hemimandibulectomy in which follow - up was performed at regular intervals , up to 6 years after surgery , using panoramic images .\nthe authors used linear and angular measurements to calculate the ratio between the operated and unoperated side to evaluate overgrowth versus growth retardation .\nalthough this approach is inaccurate , as panoramic images are prone to positioning errors and unpredictable distortion between successive images and within the same image;19 significant growth of the ccg along the vertical dimension was evident .\nko et al.13 accurately used landmarks on lateral and posteroanterior cephalometric radiographs to assess ccg growth .\nthe authors noted that the follow - up period was critical when evaluating overgrowth ; the longer the follow - up period , the more growth they found in their sample .\njang et al.20 described the case of a ccg extending from the angle of the mandible and replacing the condyle using ct .\nthe graft appeared stable with no signs of resorption or overgrowth at 10 months after surgery .\nschatz and ginat8 pointed out that autografts have the disadvantage of resorption hindering their cosmetic effect .\nthe authors demonstrated a low - attenuation cartilage graft with a peripheral rim of ossification using an axial mdct image .\nkaracaolan et al.21 also demonstrated that cartilage grafts had a tendency to undergo resorption , using magnetic resonance imaging ( mri ) after a 12-month follow - up period to assess the degree of resorption .\nthe majority of the grafts had a low signal with a few foci of high signal near the soft tissue periphery on follow - up imaging .\nno article in the literature described similar growth or changes in synthetic cosmetic implants in the soft tissue .\nhowever ; cosmetic implants , like autogenous grafts , can become incorporated into the underlying bone .\nother complications associated with cosmetic implants include migration , extrusion , erosion , and foreign bone reaction.8 with the increased use of radiographic imaging to diagnose and treat a variety of dental and medical conditions , there is an increased likelihood of incidental findings , such as implants that were not expected based on the patient 's history .\na history of implants for cosmetic purposes may not be elicited because the patient may not feel that they are important to the issue being discussed .\nalthough most implants and grafts will present as benign - looking entities within the soft tissue that can easily be interpreted as such , some may present as unusual entities that may mimic a more serious disease , such as a benign or malignant neoplasm .\nthe common management of facial defects in oavs includes reconstructive surgery , often using implants or grafts to improve patients ' cosmetic appearance .\nwe present the case of an incidentally found cosmetic graft . according to the patient ,\nan autogenous rib graft was harvested and sectioned to augment the mandibular symphysis . on imaging ,\nattempts to recover previous medical and surgical notes were unsuccessful , as the surgeon who performed the procedure in 1950 was deceased .\nthe exact surgical technique used was unclear ; however , the graft had maintained its proper anatomical location and aesthetic shape for over 65 years .\nthe most probable surgical technique may have involved the surgeon dicing the osteocartilage into multiple pieces and creating a tunnel between the mandibular periosteum and overlying mucosa to hold the diced cartilage graft in place during the healing period.21 to our knowledge , this is the last published case of an anterior mandibular costochondral graft . no case with long - term follow - up\nhas been published and a review of the literature concerning imaging related to cosmetic facial grafts did not identify any similar cases .\nclinical correlations , imaging , and histology were essential to render a final diagnosis of costochondral graft material .\nthe histopathology suggested a benign cartilaginous process ; however , the anterior mandible is a rare site for benign cartilaginous neoplasms , and without proper clinical and radiographic correlations the lesion could have been misdiagnosed .\nhowever , mandibular osteochondromas have almost exclusively been reported in the condyle.22 the characteristic imaging findings of an osteochondroma , involving a pedunculated or sessile bony cortical mass continuous with the underlying bone , were absent .\nfacial implants and grafts are found incidentally in many cbct studies performed for dental treatment .\na thorough knowledge of their normal appearance is important in order to recognize what is abnormal .\nbased on imaging alone , chondrosarcoma was initially considered due to the speckled diffuse flocculent calcification and the infiltration into adjacent normal bone .\nchondrosarcomas occur where cartilaginous tissues may be present and may occasionally occur in the symphyseal region.23 schatz and ginat8 discussed the imaging appearance of these augmentation materials using ct and mri .\nchin augmentation materials such as hydroxyapatite , silicone implants , and cartilage grafts have been described .\nthe authors concluded that cartilage grafts appear to have a soft tissue density that may form a rim of calcification or ossification.8 our case involved a more diffuse calcification pattern , which may have been due to the longer follow - up period .\nalthough most are well defined and radiographically homogeneous , being of relatively inert non - biological material , immune reactions to some may stimulate alterations in the appearance of surrounding tissues .\nbiological implants may undergo growth and differentiation , causing their appearance to mimic neoplastic lesions .\nwe present the case of a costochondral graft in the soft tissue anterior and facial to the mandible , with changes mimicking a cartilaginous neoplasm . in light of the fact that chondrosarcomas are known to occur in the anterior rib cage , an evaluation of random growth\na vascularized graft is thought to be more controlled in growth than a nonvascularized graft .\nthis is the first case to report the cbct imaging features of a long - standing graft in the anterior mandible .", "answer": "to our knowledge , the imaging features of costochondral grafts ( ccgs ) on cone - beam computed tomography ( cbct ) have not been documented in the literature . \n we present the case of a ccg in the facial soft tissue to the anterior mandible , with changes mimicking a cartilaginous neoplasm . \n this is the first report to describe the cbct imaging features of a long - standing graft in the anterior mandible . \n implants or grafts may be incidental findings on radiographic images made for unrelated purposes . \n although most are well - defined and radiographically homogeneous , being of relatively inert non - biological material , immune reactions to some grafts may stimulate alterations in the appearance of surrounding tissues . \n biological implants may undergo growth and differentiation , causing their appearance to mimic neoplastic lesions . \n we present the case of a cosmetic autogenous ccg that posed a diagnostic challenge both radiographically and histopathologically .", "id": 388} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nVarious types of non-covalent interactions contributing towards crystal packing of halogenated diphospha-dicarbaborane with an open pentagonal belt\n\nPaper sections:\n\nInnerly and/or outerly substituted boron cluster hydrides (heteroboranes) of various architectures are known for various types of non-covalent intermolecular interactions and thus serve as good models for the evaluation and mutual comparison of various types of hydrogen, dihydrogen (diH), halogen (X), chalcogen, pnictogen (Pn) or even tetrel bonds. 1,2 The neutral nido-B 7 P 2 [C(R)] 2 H 7 cage with an open P 2 CBC pentagonal belt can be formally obtained from nido-B 11 H 11 4\u00c0 (nido-B 11 H 14 \u00c0 exists) 3 by replacing four BH vertices with two tetrel and Pn vertices. Miscellaneous dicarba dipnictogen nido eleven-vertex heteroboranes have been prepared by reacting arachno-4,5-C 2 B 7 H 13 with PCl 3 , AsCl 3 and SbCl 3 . [4][5][6] The crystal structures of 3-Cl-nido-7,8, (3) compounds are already known. [4][5][6] The crystal packing of 3 is governed by Pn-bonds. 6 In contrast to 3, it has not been possible to record the singlecrystal X-ray data of the parent nido-7,8,9,11-P 2 C 2 B 7 H 9 and nido-7,8,9,11-As 2 C 2 B 7 H 9 in sufficient quality. Interestingly, it is feasible to determine the structure of single-crystal halogenated compounds 1 and 2, revealing a supramolecular architecture mainly resulting from extensive Pn-bonding. [4][5][6] In order to proceed in the examination of the non-covalent interactions of nido-heteroboranes, we attempted to iodinate 1 (Fig. 1) by the reaction with elemental iodine in the presence of aluminum trichloride (details in ESI \u2020). The resulting 3-Cl-10-I-nido-7,8,9,11-P 2 C 2 B 7 H 7 (4) was obtained in a moderate yield of 49% and was characterized in solution in terms of multinuclear NMR spectroscopy (Table 1).
In the crystal structure of 4 (Fig. 2), four molecules have been found in the unit cell. The structure of the cage of 4 is essentially the same as found for 1 4 except for the very slight shortening of the B(10)-C(9/11) bonds inside the open P 2 CBC pentagonal belt caused by the substitution of the B(10) atom by the heavy iodine. In fact, there are only two examples of a similar structural pattern in the Cambridge Structural Database, i.e. dicarba-closo-dodecaborane-1,2-diyl-1,2-bis(diisopropylamino)diphosphines, 9 but these are heavily distorted with no option of a serious structural comparison. The discrepancy between the calculated and experimental chemical shift results from the neglect of the effect of spin-orbit (SO) coupling on the overall shielding, which is not taken into account in the GIAO-MP2 scheme. However, it has been shown that due to iodine being terminally bonded to a boron atom within a neutral boron cluster, SO coupling increases the contribution of this B atom towards overall shielding by about 20 ppm, 7,8 which would considerably improve the fit in the present case.
a Institute of Inorganic Chemistry of the Czech Academy of Sciences,
To better understand non-covalent interactions of 4, we computed its ESP potential (Fig. 3) and compared it with other recently studied analogous compounds, 1-3. Compound 1 has only one highly positive s-hole located on the P vertices. The other expected s-holes of 1 could not be defined on the P vertices due to the more positive neighboring CH vertices. The Sb and As vertices of 2 and 3 have more positive ESP surfaces than the CH vertices. Both molecules thus have three well-defined s-holes on the Pn atoms. From this point of view, the ESP surface of 4 is thus analogous to 2 and 3. Compound 4 has three s-holes located on P atoms with the same magnitude (V S,max ) of 31.5 kcal mol \u00c01 . The P vertices of 4 have even more positive ESP values than the CH vertices. The ESP surface on top of the CH vertices has the value of 28.2 kcal mol \u00c01 . Besides the s-holes located on P atoms, the 4 compound also has s-holes on the X atoms. While the I atom has a positive s-hole with the V S,max value of 6.8 kcal mol \u00c01 , the Cl atom only has a relative s-hole (i.e. the top of the Cl atom is less negative than its belt but the V S,max value is negative). The 4 compound can thus form Pn-, H-and X-bonds, the last of which are, however, less probable due to the lower V S,max values on the X atoms (Table 2). The most negative ESP surface of 4 is on the negative belt on the I and Cl atoms (the magnitudes of \u00c015.1 and \u00c012.3 kcal mol \u00c01 , respectively).
Finally, we have studied pairwise interactions in the crystal structure of 4 and compared them with those of 1, 2 and Highly-accurate MP2/CBS interaction energy (DE) values are summarized in Table 3 (see also Fig. 4). The A\u00c1 \u00c1 \u00c1B motif is the most stable motif of 4. The motif can be described as two symmetrical P 2 \u00c1 \u00c1 \u00c1I Pn-bonds. Since the Pn-bond is quite long (3.8 \u00c5), it could also be seen as a nonspecific dispersion contact with an optimal dipole-dipole arrangement. The DE value of \u00c09.5 kcal mol \u00c01 is very large, considerably more negative than the most negative bonding motifs of 1 and 2 (the DE of about \u00c06.0 kcal mol \u00c01 ), which also had two Pn-bonds. However, considering that the A\u00c1 \u00c1 \u00c1B motif of 4 has two Pn-bonds, they are weaker than the Pn-bonds of 3. Compound 3 has a binding motif that is exclusively formed by a single Pn-bond and has the DE value of \u00c06.5 kcal mol \u00c01 . 6 The A\u00c1 \u00c1 \u00c1C motif, formed by two symmetrical C-H\u00c1 \u00c1 \u00c1I-B H-bonds, has DE of \u00c06.5 kcal mol \u00c01 . The H-bond is again rather long (3.2 \u00c5). The third most stable motif is A\u00c1 \u00c1 \u00c1D with DE of \u00c06.1 kcal mol \u00c01 . It is formed by the C-H\u00c1 \u00c1 \u00c1H-B dihydrogen bond and the C-H\u00c1 \u00c1 \u00c1I-B H-bond. The C-H\u00c1 \u00c1 \u00c1H-B diH-bond is the only contact in the crystal structure of 4 with the length below the sum of van der Waals radii (2.9 \u00c5 between the H and Fig. 2 The molecular structure (ORTEP 50% probability level) and atomic numbering of 4. The selected interatomic distances [\u00c5] are: I1-B10 2.184(2), Cl1-B3 1.786(2), B2-C11 1.730(3), B2-P7 2.053(2), B3-P8 2.1117(19), B3-P7 2.113(2), B4-C9 1.732(2), B4-P8 2.0516(18), B5-C9 1.715(3), B6-C11 1.715(2), C9-B10 1.608(2), C9-P8 1.8681(17), C9-H9 0.91(3), B10-C11 1.604(3), C11-P7 1.8706(19) and P8-P7 2.1970 (6). For all the distances and other structural characteristics, see Table S2 (ESI \u2020). the center of the B-H bond; H\u00c1 \u00c1 \u00c1H and H\u00c1 \u00c1 \u00c1B distances of 2.3 and 3.0 \u00c5, respectively). The A\u00c1 \u00c1 \u00c1E motif also has all contacts much higher than the sum of the van der Waals radii (e.g. the P 2 \u00c1 \u00c1 \u00c1Cl Pn bond of 3.9 \u00c5). In summary, compound 4 (3-Cl-10-I-nido-7,8,9,11-P 2 C 2 B 7 H 7 ) was prepared by reacting 3-Cl-nido-7,8,9,11-P 2 C 2 B 7 H 8 with elemental iodine in the presence of aluminum trichloride. Its molecular structure has been characterized by NMR spectroscopy, X-ray crystallography and ab initio computations. Apart from B (10) there is a good accord between the experimental and computed 11 B chemical shifts. It is the spin-orbit coupling that is responsible for such a disagreement related to B (10). The combination of Pn-, diH and H-bonds turned out to be a driving force for the crystal packing as revealed by quantum chemical computations.
\n\nConflicts of interest\nThere are no conflicts to declare. Fig. 4 The most significant interaction motifs from the crystal structure of 3-Cl-10-I-nido-7,8,9,11-P 2 C 2 B 7 H 7 (4). The distances are in \u00c5. The positions of the H atoms have been optimized at the DFT-D3/BLYP/DZVP level. 10
", "answer": "Various types of non-covalent interactions contributing towards crystal packing of halogenated diphospha-dicarbaborane with an open pentagonal belt \u2020 Josef Holub, a Zden \u02c7ka Ru \u02daz \u02c7ic \u02c7kova \u00b4,b Pavel Hobza, * c Jindr \u02c7ich Fanfrl\u0131 \u00b4k, * c Drahom\u0131 \u00b4r Hnyk * a and Ales \u02c7Ru \u02daz \u02c7ic \u02c7ka* bWe have prepared 3-Cl-10-I-nido-7,8,9,11-P 2 C 2 B 7 H 7 by the reaction of 3-Cl-nido-7,8,9,11-P 2 C 2 B 7 H 8 with I 2 in the presence of AlCl 3 .The product was obtained in a yield of 49% and was characterized by NMR spectroscopy and X-ray crystallography. Quantum chemical calculations have demonstrated that the crystal structure is stabilized by hydrogen, dihydrogen and pnictogen bonds.", "id": 389} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is well established that the presence of neoplasms in the upper tract urothelium necessitates the en bloc removal of the ipsilateral kidney , ureter , and bladder cuff as the standard of care based on the premise that urothelial cancers are caused by a field change or defect . however , due to the morbidity associated with open nephroureterectomies , conservative management may be appropriate for poor surgical candidates .\npercutaneous and ureteroscopic techniques have been utilized in the management of urothelial tumors with percutaneous access required to treat larger of upper tract urothelial cancers being used in suitable candidates.various techniques for this approach have been reported including monopolar electrocautery , laser , rollerball , and electrovaporization .\nthe reported recurrence rates have been low , and disease - free survival is comparable to that in patients treated with nephroureterectomy . the use of monopolar electrosurgery however can interfere with cardiac pacemakers resulting in potentially fatal dysrhythmias . \nwe report the case of an upper tract urothelial carcinoma in the renal pelvis resected with bipolar cautery through percutaneous access without deactivation of the cardiac pacemaker . to our knowledge\nan 82-year - old man who was a lifelong nonsmoker presented with a history of intermittent gross hematuria .\nhis medical comorbidities included non - insulin - dependent diabetes , hypertension , hypercholesterolemia , hypothyroidism , chronic renal insufficiency ( creatinine 2.4 mg/ dl ) , multiple transient ischemic attacks , stroke , sleep apnea , peripheral vascular disease resulting in a below - knee amputation , colon resection for diverticulitis , and a vdd pacemaker ( model # 640 , vitatron , minneapolis , mn ) for bradycardia .\nhis preoperative cardiac risk was goldman class ii - iii , and he was at high risk of developing a deep venous thrombosis .\nthe retrograde pyelogram on the right side was normal , but the left retrograde pyelogram demonstrated moderate hydronephrosis in a bifid collecting system and a 2-cm filling defect in the renal pelvis with renal malrotation ( figure 1 ) .\na ct scan of the abdomen and pelvis revealed a tumor limited to the left renal collecting system with no evidence of metastases .\nretrograde pyelogram displaying a renal filling defect in a bifid renal collecting system with a malrotated kidney .\nbased on a background of renal insufficiency , the options were discussed with the patient and a tumor ablation with the holmium : yag laser and flexible ureteroscopy was carried out .\nthe ureteroscopic procedure was ineffective in completely ablating the tumor at its stalk because the ureteroscope could not fully access the tumor due to the capacious renal pelvis and renal malrotation .\nthis patient was dependent on his vdd pacemaker , thus making monopolar cautery potentially hazardous .\ntherefore , a percutaneous resection using a bipolar resectoscope was planned under a second general anesthetic without deactivating the pacemaker .\nwith the patient under general anesthesia , percutaneous access to the kidney was obtained , the tract was dilated to 30 f , and an amplatz sheath was inserted .\na resectoscope using bipolar cautery ( vista , acmi corporation , south - borough , ma ) was used to resect the tumor ( settings : cut , 6 ; coagulation , 6 ) through the amplatz sheath .\nthe operation lasted 30 minutes without any evidence of dysrhythmias or interference with the pacemaker .\na 22 f nephrostomy tube was left indwelling until postoperative day 1 when it was removed , and the patient was discharged home without any complications .\nthe patient used a continuous positive airway pressure ( cpap ) machine postoperatively that helped prevent any postoperative respiratory complications .\nthe patient was seen in follow - up at 3 months with an intravenous pyelogram ( ivp ) that was free of any filling defects and negative cytology .\nserum creatinine increased only slightly from 2.4 mg / dl ( preoperatively ) to 2.6 mg / dl , postoperatively . at 8 months\n, a retrograde pyelogram revealed a recurrence of his upper tract tumor that was too large for ureteroscopic management , and percutaneous bipolar resection was once again undertaken .\nthe patient declined upper tract bacille calmette - gurin therapy and laparoscopic nephroureterectomy due to his declining health including a recent cerebral vascular accident . at 6 months ,\nthe patient remains free of recurrent or metastatic disease with stable renal function ( 2.5 mg / dl ) .\nbipolar electrocautery was introduced over 20 years ago as an energy source for endourologic procedures .\nthe potential benefits of bipolar energy include the use of isotonic normal saline irrigation and improved hemostasis .\nimportantly , it can also be used on patients with permanent cardiac pacemakers and has been described in a case involving transurethral resection of a bladder tumor in a similar pacemaker - dependent patient .\nelectrocautery - induced cardiac pacemaker failure or malfunction has been well described.since the invention of cardiac pacemakers nearly 50 years ago , electromagnetic interference has been a concern for patients who wear them . over the years , despite improved technology , permanent cardiac pacemakers remain susceptible to this electromagnetic interference , including electrocautery , during surgical procedures . traditionally , the use of monopolar electrosurgery is avoided in patients with cardiac pacemakers because the monopolar current passes from the instrument tip through the patient 's body towards the ground plate and may adversely affect the pacemaker , resulting in potentially fatal dysrhythmias .\nbipolar electro - surgery can reduce the level of interference between electrocautery units and pacemaker electrodes . \n \nbipolar electrosurgery has also been shown to reduce the depth of thermal damage at the site of surgery . in an ex vivo\nporcine kidney model , wendt - nordahl et al compared the effects of the vista bipolar system to monopolar cautery .\nthe depth of thermal damage was significantly deeper at 300 m measured with the monopolar resectoscope but only reached 160 m with the bipolar device even at the highest output level ( level 8) .\nexcessive heat may cause problems with the urothelium of the renal collecting system or penetrate deeply into parenchyma resulting in arteriovenous fistulae .\nhowever , in patients with significant medical comorbidities who are not candidates for radical surgery , bipolar resection through a percutaneous access is an alternative .\ngiven the patient 's cardiac status , a bipolar resectoscope was used not only to perform tumor resection but also to minimize the risk of electrical interference with the pacemaker .\nboth ureteroscopy and percutaneous laser ablation would have been tedious due to tumor size and location .\ndisease recurrence occurred due to multifocality and not due to failure of the initial bipolar procedure .\nit can be argued that the patient underwent 2 endoscopic procedures while under general anesthesia , whereas a laparoscopic nephroureterectomy would have offered treatment in a single procedure ; however , the single procedure would have required more surgical time in one sitting and is much more invasive than 2 short endoscopic procedures . the mortality and morbidity risk would be higher with a nephroureterectomy than 2 shorter endoscopic procedures . \nwhile the use of the bipolar electrocautery may be advantageous in the percutaneous resection of upper tract urothelial tumors , potential drawbacks of this technique include limited utility depending on tumor location and access , and dessication of the tissue creating more artifacts for pathological examination .\nit is advisable to perform a cold biopsy of the tumor for both pathology and margin status before using the bipolar electrocautery .\nmore importantly , this approach is not a replacement for nephroureterectomy but may be an option for nonsurgical candidates or patients who may benefit from nephron - sparing procedures\n. it may be a palliative procedure in some cases and potentially therapeutic in others . as illustrated in this case\n, the use of bipolar electrocautery circumvents the potential risks of using electrocautery in patients with cardiac pacemakers .\nbipolar electrocautery is a safe and feasible resection modality in percutaneously approached upper tract urothelial neoplasms in patients with cardiac pacemakers .", "answer": "percutaneous approaches to upper tract urothelial cancers have been performed in patients unsuitable for radical nephroureterectomy . \n we present the case of an 82-year - old man with significant comorbidities including dependency on a cardiac pacemaker . without deactivating the pacemaker , we used bipolar cautery to percutaneously resect a large upper tract urothelial tumor in the renal pelvis . \n bipolar cautery is a suitable method of percutaneous or transurethral resection in patients who are pacemaker dependent .", "id": 390} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbetween july 2010 and june 2013 , 385 csf cytology samples were collected from 42 patients with the presence of a metastatic tumor confirmed by at least two histologic or cytological studies .\ncytology samples obtained before adjuvant therapies were excluded to evaluate the diagnostic rate of csf cytology more consistently .\nthe breakdown of the patient population was as follows : 25 males and 17 females , with a median age of 55 years ( range , 29 to 77 years ) .\nthe mean observation period was 5 months ( range , 1 to 22 months ) , and the mean number of csf examinations was 9 ( range , 2 to 34 ) .\nall patients underwent an operation for the placement of a ventricular catheter and reservoir as well as consecutive csf collections using the reservoir ( fig .\nto minimize dry artifacts and prevent cell degeneration , samples were delivered to the department of pathology immediately upon collection .\nsamples were then processed using liquid - based cytology ( lbc ) ( thinprep , cytyc co. , boxborough , ma , usa ) , an automated method of preparation and smearing of cells in a monolayer .\nof the 385 csf samples , 54 were processed by a conventional smear method rather than the liquid - based method because those samples were obtained when the liquid - based method was not available for csf cytology .\nimmunocytochemistry ( icc ) was performed using a ventana xt automated stainer ( ventana co. , tucson , az , usa ) with an antibody to cytokeratin ( 1:300 , ae1/ae3 , dako , carpinteria , ca , usa ) .\nslides were incubated with primary antibody for 32 minutes at 37 followed by a universal secondary antibody for 8 minutes at 37. slides were incubated in streptavidin - horseradish peroxidase d for 16 minutes at 37 , and then the substrate , 3,3'-diaminobenzidine tetrahydrochloride ( dab ) h2o2 , was added for 8 minutes , followed by hematoxylin and bluing reagent counterstains at 37. cases without atypical cells suggestive of metastasis were diagnosed as negative for malignancy .\na positive diagnosis of malignancy was defined as the presence of atypical cells with cytokeratin immunoreactivity , regardless of the amount ( fig .\n2 ) . there were some cases that presented with atypical cells on papanicolaou - stained slides , but it was not possible to evaluate many of these cases using cytokeratin icc slides because the cells disappeared during the staining process . in those cases , we termed the diagnosis suspicious for malignancy , and these cases were regarded as positive findings when calculating the diagnostic rates .\nall slides , including those for icc , were independently reviewed by two pathologists ( s.h.k and y.s.b ) .\nbetween july 2010 and june 2013 , 385 csf cytology samples were collected from 42 patients with the presence of a metastatic tumor confirmed by at least two histologic or cytological studies .\ncytology samples obtained before adjuvant therapies were excluded to evaluate the diagnostic rate of csf cytology more consistently .\nthe breakdown of the patient population was as follows : 25 males and 17 females , with a median age of 55 years ( range , 29 to 77 years ) .\nthe mean observation period was 5 months ( range , 1 to 22 months ) , and the mean number of csf examinations was 9 ( range , 2 to 34 ) .\nall patients underwent an operation for the placement of a ventricular catheter and reservoir as well as consecutive csf collections using the reservoir ( fig .\nto minimize dry artifacts and prevent cell degeneration , samples were delivered to the department of pathology immediately upon collection .\nsamples were then processed using liquid - based cytology ( lbc ) ( thinprep , cytyc co. , boxborough , ma , usa ) , an automated method of preparation and smearing of cells in a monolayer .\nof the 385 csf samples , 54 were processed by a conventional smear method rather than the liquid - based method because those samples were obtained when the liquid - based method was not available for csf cytology .\nimmunocytochemistry ( icc ) was performed using a ventana xt automated stainer ( ventana co. , tucson , az , usa ) with an antibody to cytokeratin ( 1:300 , ae1/ae3 , dako , carpinteria , ca , usa ) .\nslides were incubated with primary antibody for 32 minutes at 37 followed by a universal secondary antibody for 8 minutes at 37. slides were incubated in streptavidin - horseradish peroxidase d for 16 minutes at 37 , and then the substrate , 3,3'-diaminobenzidine tetrahydrochloride ( dab ) h2o2 , was added for 8 minutes , followed by hematoxylin and bluing reagent counterstains at 37.\ncases without atypical cells suggestive of metastasis were diagnosed as negative for malignancy . a positive diagnosis of malignancy was defined as the presence of atypical cells with cytokeratin immunoreactivity , regardless of the amount ( fig .\n2 ) . there were some cases that presented with atypical cells on papanicolaou - stained slides , but it was not possible to evaluate many of these cases using cytokeratin icc slides because the cells disappeared during the staining process . in those cases , we termed the diagnosis suspicious for malignancy , and these cases were regarded as positive findings when calculating the diagnostic rates .\nall slides , including those for icc , were independently reviewed by two pathologists ( s.h.k and y.s.b ) .\nlung was the most common primary site with 22 cases , followed by breast with 6 cases .\nof the 385 specimens , 132 were diagnosed as positive for malignancy and 27 were suspicious for malignancy , for a total of 159 specimens considered to have a positive diagnosis of malignancy . among the 42 patients ,\n3 were never diagnosed as malignant by cytology examination even though all were confirmed to have cns metastasis on brain tissue biopsy .\nthe positive malignancy diagnosis rates in the other 31 patients ranged from 4.5% to 87.5% , and the mean positive rate was 41.3% .\ntable 2 demonstrates two representative cases ( case nos . 4 and 12 ) from our series .\nduring a period of two months , these two patients underwent 13 and 15 csf cytology examinations , which yielded positive results in 6 and 10 of the tests , respectively .\nthe intervals between csf cytology examinations ranged from 0 to 13 days and were short enough to enable more meticulous analysis of consecutive diagnostic rates . however , the results appeared random , without a consistent trend . even within the same day ,\nrapid transport is important for optimal cellular preservation in csf materials , which can be cytolysed quickly . in order to reduce the number of nondiagnostic cases ,\ncsf materials should be examined as soon as possible after collection . from a routine diagnostic viewpoint ,\ndegeneration is one of the most problematic artifacts when diagnosing cytology slides , as csf specimens tend to degenerate more readily than other cytology specimens .\nwe were able to control artificial factors by reminding clinicians of the importance of rapid processing and encouraging them to submit the samples immediately .\nmost previous studies concerning the diagnostic rates of csf examination used the lumbar puncture as a diagnosing modality.4 - 6 however , lumbar puncture can be harmful to patients and difficult for clinicians because it is an invasive procedure .\nit is this for reason that most previous studies regarding the diagnostic accuracy of csf performed only one csf examination per patient . in this study , however , consecutive csf sampling was performed using the ventricular catheter and reservoir from each patient .\nalthough a neurosurgical procedure is required to implant a ventricular catheter in patients , it enables the continuous collection of csf and consecutive analysis .\nlbc is now a widely used method for preparing cytology samples and has achieved broad acceptance for most cytology specimens.8 - 11 furthermore , for the diagnosis of metastatic tumors in csf , thin - layer lbc has been suggested as an appropriate diagnostic method.12,13 as in immunohistochemistry , icc improves the diagnostic rates because cytology is often difficult and problematic to evaluate using cellular morphology alone.14 using lbc is more convenient for performing icc than conventional smear techniques , and the diagnostic efficacy of icc on smears processed by thin - layer lbc has been previously validated.15 - 17 up to the present time , there have been several reports regarding the diagnostic accuracy of csf cytology in patients with cns metastasis .\nwasserstrom et al.5 reported a sensitivity of 54.4% in initial examination and 91.1% in subsequent examination .\neven though we used implanted ventricular catheters when obtaining csf and lbc when preparing csf slides , results of our study showed much lower diagnostic rates than previous studies .\nthe discrepancy between results of previous studies and ours might be due to the different process of gathering csf ; unlike previous studies , we tried to evaluate the diagnostic rates of csf cytology using consecutive examination of csf samples from each patient .\nmoreover , in our study , samples were obtained from patients receiving adjuvant treatments such as chemotherapy and radiation therapy , which may have affected the diagnostic rates of csf analysis . from the viewpoint of daily practice\n, our results may be more practical and accurate because most patients with cns metastasis are now managed with ancillary treatments.7 we could not analyze the results of csf examinations with statistics of sensitivity or specificity because not all cytology specimens had a concordant tissue biopsy .\nin other words , the negative findings could not be directly considered as false negatives because we could not completely exclude the possibility that the negative findings resulted from true tumor regression due to adjuvant therapies . however , as shown in table 2 , results were distributed unevenly although all examinations were performed within very short intervals , even within the same day in some cases .\ntherefore , we suggest that the negative findings are not the results of tumor regression but false negative results . if so , the value of 41.3% can be regarded as sensitivity of csf cytology in patients being treated with adjuvant therapies due to cns metastasis .\nfirst , several factors influencing the quality of csf cytology specimens should be investigated . in our study ,\nhowever , this can not be the reason for the negative results because csf is physiologically acellular .\nthe volume of the submitted specimen can affect the diagnostic accuracy , but unfortunately this aspect was not evaluable because the amount of fluid was not promptly recorded .\ndry artifact is one of the most important factors in determining the quality of csf slides . as mentioned earlier , we could maintain the quality of csf cytology by notifying clinicians of the importance of rapid transport .\nhowever , specimen transport could not be controlled precisely and evenly because the specimens were transported by different clinicians with different time intervals .\nthere was no significant difference among negative results when grouped according to the sites of primary tumors ( data not shown ) .\ntaken together , the negative results should be regarded as a multifactorial phenomenon without a specific reason .\ntemporary csf cytology examinations are no longer sufficient for estimating clinical course because chemotherapy and optional radiotherapy are generally standard treatment modalities in patients with cns metastasis .\nalthough the total number of cases included was not remarkable , this study is noteworthy in that we tried to evaluate the diagnostic rates of csf cytology in a novel way . by analyzing consecutive csf samples obtained within short - term intervals ,\nwe were able to evaluate the diagnostic rates of csf examination more precisely and more practically .\nalthough the sensitivity of csf cytology as a diagnostic tool in patients with cns metastasis was lower than expected , even with the icc , we consider this result to be important and instructive as negative results should not be ignored or regarded as tumor regression . alternatively ,\ncontinuous follow - up using csf cytology is essential for determining clinical course , and the results must be interpreted in conjunction with clinical and radiological findings .", "answer": "backgroundcerebrospinal fluid ( csf ) examination can be used to verify the presence of primary malignancies as well as cases of central nervous system ( cns ) metastasis . \n because of its importance , there have been several studies concerning the sensitivity of csf cytology . to determine the practical use and reproducibility of diagnoses based on csf cytology \n , we evaluated this test by analyzing cytology results from consecutive csf samples.methodsbetween july 2010 and june 2013 , 385 csf cytology samples from 42 patients were collected . \n the samples were gathered using a ventricular catheter and reservoir . \n csf cytology of all patients was examined more than two times with immunocytochemistry for cytokeratin.resultsprimary neoplastic sites and histologic types of patients ' metastatic cancer were diverse . \n the overall sensitivity for detecting malignancy was 41.3% . \n even within short - term intervals , diagnoses frequently changed.conclusionsour results were inconsistent , with low sensitivity , when compared to the results of previous studies . \n however , csf evaluation can still provide valuable diagnostic and prognostic information because adjuvant treatments are now routinely performed in patients with cns metastasis . \n negative csf cytology results should not be ignored , and continuous csf follow - up is essential for following the clinical course of patients with metastatic cancer involving the cns .", "id": 391} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndespite many years of research efforts and impressive progress in knowledge of mechanisms of endometriosis development , the etiopathogenesis of the disease and exact cause of infertility in patients suffering from endometriosis still remain poorly understood .\nnone of the theories and models of endometriosis pathogenesis provide definitive explanation of the disease development , considering its different manifestations and various localizations .\nrecently published studies present new data on potential role of free radicals in endometriosis pathophysiology .\nalthough the origin of the oxidative stress occurring in the peritoneal cavity in endometriotic patients is unknown , accumulating data suggest that increased iron levels , together with apoptotic endometrial fragments and activated macrophages , may promote prooxidant environment .\nin addition , oxidative stress in endometriotic patients may potentially be induced by environmental factors , including dioxins or heavy metals [ 1 , 2 ] . in our preliminary work\nwe found significantly increased levels of ox - ldl in peritoneal fluid of women with stage iii / iv endometriosis compared to patients with follicle ovarian cysts .\nhowever , peritoneal fluid oxldl concentrations did not differ significantly between patients with minimal / mild endometriosis and women from the reference group .\nmurphy et al . showed increased low - density lipoprotein ( ldl ) oxidation in peritoneal fluid of patients with endometriosis , which may be a result of peritoneal cavity macrophages hyperactivity .\nit was also proved that oxidized ldls stimulate monocyte chemotactic protein-1 ( mcp-1 ) expression in mesothelial and endometrial cells which provides direct evidence of oxidative stress role in etiopathogenesis of the disease . increased concentrations of lipid peroxidation end products , malondialdehyde ( mda ) , 8-isoprostane , and 25-hydroxycholesterol , were found in peritoneal fluid of infertile women with endometriosis [ 610 ] .\nserum of patients with endometriosis , compared to healthy women , contains also significantly higher 8-isoprostane levels .\nmurphy et al . showed that peritoneal fluid of patients with endometriosis contains increased concentration of lysophosphatidylcholine , another lipid peroxidation product with confirmed chemotactic properties for monocytes .\nmda and 7-hydroxynonenal ( hne-7 ) expression were increased in endometriosis implants tissue ; however , both lipid proteins are also expressed in eutopic endometrium .\nconcentrations of antibodies against lipid peroxidation products were found to be increased in serum of women with endometriosis , with no immunoglobulins detected in their peritoneal fluid .\nserum of women with endometriosis contains also elevated concentration of lipid hydroperoxide ( looh ) , and its levels correlate positively with the stage of the disease according to revised american fertility society classification .\nperitoneal fluid of endometriotic patients contains oxidatively modified protein - lipid complexes , showing both chemotactic properties and ability to stimulate selected cytokines production . however , there are relevant data published in the literature according to which the concentrations of mda and mda - cu complexes demonstrate no significant differences , being comparable in peritoneal fluid of patients with and without endometriosis , showing also no significant correlation with the stage of the disease [ 1618 ] .\nno differences were also found in peritoneal fluid concentration of another lipid peroxidation product , cholest-3,5-dien-7-one .\nthe objective of the study was to assess concentrations of oxidized low - density lipoproteins ( oxldl ) in peritoneal fluid ( pf ) of women with endometriosis .\nclinically and histologically confirmed diagnosis established the following groups : women with endometriosis ( e , n = 110 ) and as the reference groups : patients with simple serous ( r1 , n = 78 ) and dermoid ( r2 , n = 41 ) ovarian cysts . in each case\nthe disease was found to be minimal ( e1 ) in 23 cases , mild ( e2 ) in 25 patients , moderate ( e3 ) in 39 women , and severe ( e4 ) in 23 cases . \nsubjects were not given hormonal therapy and/or anti - inflammatory medications for at least 3 months before laparoscopy .\nmedical history of the patients and basic clinical examination showed no general chronic diseases , except for the condition , which was the indication for laparoscopy .\nsimilarly , no significant difference was found in the phase of menstrual cycle of the time of laparoscopic procedures between women in all study groups .\nall patients signed an informed consent , and the lublin medical university ethics committee approval was obtained for the study .\nall visible pfs were aspirated during laparoscopy from the anterior and posterior cul - de - sacs , under direct vision to avoid blood contamination .\nsamples were immediately centrifuged at 500 g for 5 minutes , and the supernatants were aspirated and stored at 70c until analysis .\noxldl concentration in the pf was measured in duplicate using a commercially available enzyme - linked immunoassay kit ( immundiagnostik ag , cat .\nall data were tested with the shapiro - wilk test for normality . because data were not normally distributed , statistical significance between e and r groups was determined with the mann - whitney u test .\ndata are presented as medians ( me ) , minima ( min ) , maxima ( max ) , and lower and upper quartiles .\nconcentrations of oxldl in pf of patients with endometriosis were significantly higher compared to women with serous ovarian cysts ( p = 0.03 ) .\nhowever , no significant difference in the pf oxldl levels was found between patients with endometriosis and women with dermoid ovarian cysts ( p = 0.4 ) .\nlevels of oxldl in pf of women with serous ovarian cysts were similar to those noted in patients with dermoid cysts ( figure 1 , table 1 ) . by analyzing concentrations of oxldl in pf of women with different stages of the disease\n, it was noted that they were higher only in the subgroup of patients with stage iv endometriosis as compared to women with ovarian serous cysts .\nno significant differences were found between concentrations of oxldl in pf of women with different stages of the disease ( table 2 ) . \npf oxldl concentration did not differ significantly between the subgroups of women in the follicular and the luteal phase of the menstrual cycle ( me , range : 71.5 , 1.21470 ng / ml versus 80.3 , 16.71870 ng / ml , p = 0.5 ) .\nin our work , we demonstrated that peritoneal fluid oxldl concentration was significantly higher in patients with endometriosis than in women with serous ovarian cysts ; however , it did not differ significantly as compared to subjects with dermoid cysts . after analysis of data obtained in women with different stages of the disease , it was noted that these results are found only in patients with severe endometriosis . in case of minimal , mild , and moderate disease ,\nto our knowledge , only murphy and colleagues investigated the possible role of oxldl in the pathogenesis of endometriosis .\nbased on a small number of cases , they found increased oxidation of low - density lipoprotein in women with pelvic endometriosis and increased levels of oxldl in the pf of patients with this disease .\nour results agree with these findings . however , our data suggest that only the severe stage of endometriosis is associated with increased oxidation of low - density lipoprotein in the peritoneal cavity , probably as the result of an imbalance in prooxidant / antioxidant pf systems .\nshanti et al . demonstrated that women with endometriosis had increased serum concentrations of autoantibodies to markers of oxidative stress including oxldl .\ndata from our work indirectly confirm these results . based on many findings , there is an emerging concept of treating endometriosis as an autoimmune disease .\nan increased incidence of endometriosis was observed in the group of women with autoimmune diseases such as multiple sclerosis , lupus erythematosus , psoriasis , crohn 's disease , hypothyroidism , hyperthyroidism , and rheumatoid arthritis .\nendometriosis shares many similarities with other autoimmune diseases including elevated levels of cytokines , decreased cell apoptosis , and t- and b - cell abnormalities .\na variety of autoantibodies have been detected in patients with endometriosis patients , which suggests a polyclonal activation of b cells .\nthe most commonly reported types are antiendometrial , antiovarian antibodies , and autoantibodies against phospholipids , histones , and nucleotides\n. other similarities between endometriosis and autoimmune diseases include familial occurrence , tissue damage , preponderance of females , and multiorgan involvement [ 21 , 22 ] .\nlipid peroxidation processes are closely associated with the pathophysiology of autoimmune diseases . therefore , increased levels of oxidized ldl in pf of women with endometriosis support the theory of treating endometriosis as an autoimmune disease .\noxidized ldl induces secretion of numerous proinflammatory cytokines including macrophage colony - stimulating factor ( m - csf ) , interleukin-6 ( il-6 ) , and tumor necrosis factor ( tnf- ) .\nconcentrations of these cytokines were found to be elevated in the pf of patients with endometriosis .\nwe can speculate that increased levels of oxidized ldl in the peritoneal cavity of women with severe endometriosis may be one of the factors responsible for increased levels of m - csf , il-6 , and tnf- in pf .\nelevated pf concentrations of these cytokines promote adhesion , invasion , proliferation , and angiogenesis of ectopic endometrium and create an inflammatory environment in the peritoneal cavity in women with endometriosis .\n. demonstrated that oxldl caused an increase in accumulation of monocyte chemotactic factor-1 ( mcp-1 ) in the medium of cultured mesothelial and endometrial cells .\nthey also found that cells cultured in the presence of pf from endometriosis patients secreted more mcp-1 than those cultured with pf from subjects without the disease .\ntherefore , we hypothesize that increased concentration of oxldl may be responsible for , as demonstrated in other studies , higher concentrations of mcp-1 in the pf of women with endometriosis .\nstimulation of mcp-1 production by increased pf levels of oxidized ldl may hypothetically be another factor responsible for the creation of proinflammatory environment in the peritoneal cavity of patients with endometriosis . \nunfavorable changes in lipid profile are present not only in the pf of women with endometriosis .\nit has been recently shown that plasma of patients with this disease contains higher concentrations of total cholesterol , low - density lipoproteins , high - density lipoproteins ( hdl ) and triglycerides as compared to healthy women .\nalthough all lipoproteins were significantly elevated in endometriosis patients , the difference was most substantial for ldl levels , which were 38% higher in women with endometriosis .\nverit et al . found that patients with endometriosis displayed significantly lower serum levels of hdl and higher levels of triglycerides , total cholesterol , and ldl than women without the disease .\nthey also demonstrated that serum of women with endometriosis is characterized by significantly lower activity of paraoxonase-1 ( pon-1 ) , which negatively correlated with the progression of the disease .\nthis hdl - associated antioxidant enzyme with paraoxonase activity prevents ldl and hdl oxidation and is also responsible for the antioxidant effect of hdl .\ntherefore , authors speculated that unfavorable lipid profile combined with lower pon-1 activity in women with endometriosis may contribute to the increased susceptibility for the development of atherosclerosis . in conclusion ,\noxldl levels were significantly higher in the peritoneal fluid of patients with severe endometriosis than in women with serous ovarian cysts .\nthis suggests that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the etiopathogenesis of the more advanced stages of the disease .\nhowever , it can not be excluded that high oxldl levels are the result of more oxidant environment in the peritoneal cavity of patients with severe endometriosis than with less advanced disease .", "answer": "the etiopathogenesis of endometriosis still remains unknown . \n recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease . \n it has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid ( pf ) and serum of endometriotic patients . \n we assessed the concentration of oxidized low - density lipoproteins ( oxldl ) in pf of 110 women with different stages of endometriosis and 119 women with serous ( n = 78 ) or dermoid ( n = 41 ) ovarian cysts , as the reference groups . \n pf oxldl levels were evaluated by elisa . \n we found that concentrations of oxldl in pf of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts . \n interestingly , by analyzing concentrations of oxldl in women with different stages of the disease , it was noted that they are significantly higher only in the subgroup of patients with stage iv endometriosis as compared to women with ovarian serous cysts . in case of minimal , mild , and moderate disease , \n pf oxldl levels were similar to those noted in reference groups . \n our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease .", "id": 392} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngeneralized convulsive status epilepticus ( gcse ) and non - convulsive status epilepticus ( ncse ) are important neurological conditions potentially associated with significant morbidity and mortality.1 even with the best current practice , the mortality of patients with refractory gcse is up to 50% .\ntherefore , there is an urgent need for new treatment options that can treat these seizures safely and more effectively than the current standard drugs.2 the most common treatment protocols for status epilepticus include an intravenous benzodiazepine , either lorazepam ( lzp ) or diazepam , as the initial antiepileptic drug ( aed ) therapy , followed by phenytoin ( dph ) or fosphenytoin .\nphenobarbital ( pb ) is added if the seizures continue.3 a pharmacologically induced coma , using the barbiturates , propofol or midazolam , is also a frequently used therapy for refractory status epilepticus ( rse),2,4,5 which is defined as the persistence of discrete seizures without return to baseline , despite treatment with benzodiazepines and at least two adequate aeds.6,7 however , it requires artificial ventilation and hemodynamic support , and is associated with significant complications and increased mortality.2,4 topiramate ( tpm ) is an aed with demonstrated efficacy for a broad spectrum of seizure types8 ; it has multiple activities at receptors and ion channels that may be more effective than conventional anticonvulsants in treating rse.7,9 we report our experience with the use of tpm for the treatment of benzodiazepine - refractory status epilepticus ( se ) or recurrent seizures in 16 patients who are under severe medical complications such as systemic infection , renal dysfunction , hepatic dysfunction , and pancytopenia from bone marrow suppression .\nwe retrospectively identified patients with gcse or ncse who were treated with tpm at our hospital between july 15 , 2006 and august 10 , 2008 .\nthe medical records were reviewed for information regarding patient characteristics , associated medical conditions , type of se ( gcse or ncse ) , duration , abnormal laboratory findings , treatment history prior to administration of tpm , and outcome .\nhepatic dysfunction was defined as an ast and alt > 200 mg / dl and renal dysfunction was defined as a serum creatinine > 2.0 mg / dl and a creatinine clearance < 0.6 .\nanemia was defined as a hemoglobin < 12.0 g / dl , thrombocytopenia as a thrombocyte count < 150,000/mm and pancytopenia as a leukocyte < 4,000/mm with anemia and thrombocytopenia . administration of aeds , other than tpm , followed our hospital s protocol : lzp ( 4 mg ) was injected intravenously and dph ( 15 mg / kg ) or vpr ( 20 mg / kg ) were infused intravenously for 30 minutes .\nthe mixture was allowed to sit for several minutes to avoid clumping and then administered via syringe into a nasogastric tube .\nthe loading dose was individualized by patient ; 612 mg / kg / day , up to 1,000 mg / day .\nthe resolution of recurrent gtc and gcse was determined by cessation of clinical seizures , and confirmed by follow - up electroencephalopgrahy ( eeg ) . for ncse ,\nfrom the database on se patients , 16 patients were identified for inclusion in this study .\nno patient had a history of seizures or was receiving tpm or other aeds prior to admission .\nthe most common previous , co - morbid disease at the onset of seizures was sepsis ( n=8 ) .\nthe laboratory studies showed that 12 patients had hematological problems ( pancytopenia 8 , anemia alone 2 , and anemia with thrombocytopenia 2 ) .\nseven patients had renal dysfunction , three patients had hepatic dysfunction only and another four patients had both renal and hepatic dysfunction .\nthe majority of patients had experienced gcse ( n=6 ) or ncse ( n=7 ) .\nthe mean tpm treatment dose was 637.5244.6 mg ( 3001,000 mg ) . within a few days\n, 13 patients could experience their seizure control ( the mean duration , 3.72.6 days ; range 18 days ) , but the seizures of the other 3 subjects did not be terminated in spite of all efforts . none of the patients had a worsening of their cbc or blood chemistry profiles with the tpm treatment . for seven patients ,\nthe tpm was administrated after the failure of the loading of high doses of dph or vpr .\nthe administration of tpm was within 2 hours after the infusion of dph or vpr .\nthe overall outcome was described as follows : patient death ( n=11 ) , improved ( n=4 ) , transferred to another hospital ( n=1 ) .\nthe causes of 11 deaths were sepsis ( n=7 ) , fulminant hepatitis , sah , hypoxic brain damage , and herpes encephalitis .\nwe now represent two illustrative cases using tpm for controlling recurrent seizures from a variety of medical derangement .\na 48-year - old woman with no history of seizures was admitted to the hospital in poor health .\nthe patient was diagnosed with paroxysmal nocturnal hemoglobinuria ( pnh ) 20 years prior to admission and had been treated as an outpatient with oral steroids .\nthe routine blood tests on admission revealed pancytopenia ( hemoglobin 4.4 g / dl , hematocrit 13.3% , wbc 730/mm , and a platelet count of 52,000/mm ) and acute renal failure ( bun 126.5 mg / dl and creatinine 9.23 mg / dl ) .\ncontinuous renal replacement therapy ( crrt ) was performed in the intensive care unit . on the third hospital day , gcse developed .\na loading dose of tpm ( 800 mg ) was administrated via a nasogastric tube . by the next day ,\nhowever , intermittent brief seizures occurred several times under a maintenance dose of tpm ( 300 mg bid ) during the subsequent two days .\nthe diffusion - weighted mri revealed multifocal high signal intensity involving the occipital lobes , the right basal ganglia and the subcortical white matter of the prefrontal gyri on the diffusion and t2-weighted images .\nthe identified lesions showed increased values on the adc map , suggesting vasogenic edema or a posterior reversible encephalopathy ( pres ) .\nthe tpm was maintained at a dose of 200 mg bid , and there was no further seizure activity .\nhowever , aspiration pneumonia and sepsis developed , and the patient died on the 15th hospital day .\na 56-year - old woman was admitted to the hospital with impaired mental status . the patient had a history of multiple myeloma ( stage iiia ) diagnosed three years prior to the admission\nvad chemotherapy using vincristine , doxorubicin and dexamethasone was started . however , generalized seizures developed during the third cycle of chemotherapy , and the patient became unresponsive with her eyes deviated to the right side . the routine blood tests revealed pancytopenia ( hemoglobin 5.2 g / l , hematocrit 14.4% , wbc 4,570/mm , and a platelet count of 15,000/mm ) , and septic shock developed .\nhowever , the blood culture revealed staphylococcus epidermidis , and she died on the 49th hospital day from septic shock .\nwe described 16 patients with gcse , ncse or recurrent gtc in whom tpm was administered alone or together with other aeds .\nmost patients with overt , convulsive status epilepticus respond to the first or second aed . however , when the patient fails to respond to this standard protocol during the initial treatment , the patient is considered refractory and requires additional , more aggressive treatment.3 rse is a life - threatening condition that carries a high mortality risk .\naggressive , early intervention permitting avoidance of a pharmacological coma can reduce the overall morbidity and mortality.4 current recommendations for the treatment of refractory status epilepticus include midazolam ( mdz ) , pentobarbital and propofol.10 however , respiratory depression and/or hypotension may result from this treatment , which may necessitate endotracheal intubation and/or vasopressor support .10,11 oral aeds such as tpm or lev , however , have much to offer if they can pre - empt these more aggressive managements.12 tpm has at least five independent actions at the cellular level13 : inhibition of kainate - evoked currents , enhancement of -aminobutyric acid ( gaba)-evoked currents , blockage of voltage - activated sodium channels , blockage of voltage - activated calcium channels , and inhibition of carbonic anhydrase isoenzymes .\nthe multiple mechanisms of action confer broad - spectrum efficacy against different seizure types and make tpm an attractive choice in the treatment of both partial and generalized se.14 since tpm has pleiotropic effects on neuronal excitability , a favorable pharmacokinetic profile and appears to have few side effects in the setting of rse , it is a reasonable therapeutic option in patients with se.3 tpm is also considered appropriate for treatment of patients with of hepatic or renal disease\n. it does not significantly increase the risk of hepatotoxicity and renal disease is not a contraindication to the use of tpm.15 there are some reports on the use of tpm in se patients .\n16 reported a patient with drug - resistant complex partial se who responded to tpm .\ntowne and colleagues described six adult patients with a variety of types of se who were unresponsive to conventional treatment , including two who also failed to respond to treatment with pentobarbital.7 a suspension of tpm administered by a nasogastric tube was effective in aborting the rse in all cases .\nremarkably , no adverse events were observed and all six patients who survived and were discharged from the hospital .\nbensalem et al . also described the use of tpm via a nasogastric tube in three patients with rse ( two with generalized seizures and one with partial seizures).14 tpm appeared to be very effective in stopping the rse ; in two of the patients that were resistant to either pentobarbital or propofol , and no adverse effects were noted .\npatients who had se after therapeutic doses of at least two antiepileptic medications were given tpm , 10 mg / kg / d for consecutive days , followed by maintenance doses of 5 mg / kg / d . in each case , the se was stopped within 21 hours of the initial dose of tpm . in our study , the seizures of subjects were terminated both clinically and electrographically in 13 out of 16 patients .\nthe timing of improvement in our patients was within 18 days of starting the administration of tpm .\nthese findings are consistent with the pharmacokinetic properties of tpm and previous reports . in six cases , given tpm after loading with dph or vpr failed , tpm successfully stopped the seizures , even in medically complicated patients .\nalthough seizures were stopped clinically and electrographically in the majority of our patients , the overall outcome was not very favorable in our study .\n. the high mortality rate of the patients studied reflects the large number of leukemia and lymphoma patients treated in our hospital .\nthe majority of the patients studied had serious and often life threatening hematological problems such as pancytopenia or thrombocytopenia .\nthey had a variety of medical comorbidities , including systemic infection , hepatic or renal dysfunction and hematologic / oncologic disorders .\nhowever , our results convincingly support that tpm is safe and effective in a special group of seriously ill patients .\nwe could find that tpm was not only safe but very effective for the control of recurrent epileptic seizures or se in patients with serious medical co - morbidities .\ntpm may be considered as another treatment option when conventional protocols fail . a large prospective , randomized ,\ncontrolled study is warranted to investigate the efficacy and safety of tpm for the treatment of se .", "answer": "background and purpose : the conventional therapeutic regimen for status epilepticus ( se ) may require artificial ventilation and hemodynamic support , and is associated with significant complications and increased mortality . \n we investigated the safety and effectiveness of topiramate ( tpm ) in patients with refractory se , who had medical complications such as systemic infection , renal dysfunction , hepatic dysfunction , and bone marrow suppression.methods:we analyzed the clinical features and therapeutic outcome in 16 patients with gcse , ncse or recurrent gtc in whom tpm was administered for its control.results:the majority of our patients had gcse ( n=6 ) or ncse ( n=7 ) . \n the common co - morbid diseases at the onset of seizures were hematological disorders ( pancytopenia 8 , anemia 2 , anemia with thrombocytopenia 2 ) and sepsis ( n=8 ) . \n twelve patients were under the renal and/or hepatic dysfunction . within a few days \n , 13 patients could experience their seizure control ( the mean duration , 3.7 2.6 days ) , but the seizures of the other subjects did not be terminated in spite of all efforts . \n no patients experienced a worsening of their cbc or blood chemistry profiles with the tpm treatment.conclusions:we could confirm that tpm was not only safe but very effective for the control of recurrent epileptic seizures or se in patients with serious medical co - morbidities . \n tpm may be considered as another treatment option when conventional protocols are ineffective .", "id": 393} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe endotracheal tube ( ett ) should be placed at the optimal level to avoid inadvertent complication .\nif the ett is too deep , it increases the risk of unintended single lung ventilation .\non the other hand , if the ett is too shallow , it may cause vocal cord injury by the ett balloon or accidental extubation .\nthere are many methods for determining the appropriate depth of ett in adults ; fixed insertion depth according to sex ( 23 and 21 cm from the upper incisors in adult males and females , respectively ) , the use of depth marks on the ett , suprasternal palpation of the ett tip or cuff , and bilateral auscultation .\nalthough chest radiography and bronchoscopy are considered an accurate method , they are not always feasible and the costs are considerable . considering the individual variation in the length of the trachea , using fixed depths or marks on the ett may result in inadequate placement of the ett . to reduce the risk of single lung ventilation or vocal cord injury , the segment between the proximal edge of the cuff and the ett tip should be placed at the mid - trachea level . if the length of the trachea can be predicted at bedside before intubation , the ett can be placed at a safe depth for each patient .\nthe purpose of this study was to determine whether surface anatomical landmarks can be used to predict the mid - tracheal level in adult patients .\nneck computed tomography ( ct ) images of adults obtained between 2009 and 2014 were reviewed by a single reviewer after obtaining approval form seoul national university hospital institutional review board ( july 17 , 2015/no .\npatients with laryngeal , tracheal , or thoracic abnormalities , tracheostomy or significant tracheal deviation caused by mass lesions were excluded .\nin addition , poor ct image quality , absent sagittal ct images , ct images that did not cover the entire trachea , or ct images taken in neck hyperextension ( boidin angle > 130 on scout view ) or hyperflexion ( boidin angle < 110 on scout view ) position were also excluded .\nlevels of subglottic and tracheal airway segments that include the vocal cords ( vc ) , the cricoid cartilage ( cc ) , and the carina were identified using the method described by sirisopana et al .\nthe vocal cords were identified as the most cranial level of the upper airway , with a teardrop shape below the laryngeal ventricle . anatomic level of suprasternal notch ( ssn )\nthe level of manubriosternal junction ( msj ) was defined as the middle level between the manubrium and the body of the sternum where the second rib attaches to the sternum .\nthe level of carina was defined as the bifurcation of right and left main bronchus and identified by the figure 8 shaped lumen .\nthe external locations of the cc , ssn , and msj were defined on the skin surface .\nthe distances between the external points of the cc and the ssn ( extcc - ssn ) , and those of the ssn and the msj ( extssn - msj ) were measured .\nthe distances between the subglottic structures at the levels of the vc , the cc , ssn , and carina were measured .\ntracheal length was calculated as the summation of the distances measured from the vc to the carina .\nthe mid - trachea level was calculated from tracheal length and the ideal position of ett is shown in fig .\n2 . identification of subglottic segments on axial view ( right ) , and defining the distances between subglottic segments on sagittal view ( left ) in a 45-year - old male patient .\ncc = cricoid cartilage , extcc - ssn = the surface distances from the cricoid cartilage to the suprasternal notch , extssn - msj = the surface distances from the suprasternal notch to the manubriosternal junction , msj = manubriosternal juction , ssn = suprasternal notch , vc = vocal cord , tracheal length = a + b + c + d. the ideal position of endotracheal tube ( ett ) to minimize the risk of endobronchial intubation and vocal cord injury .\nthe mid - point between the proximal edge of the cuff and the ett tip was matched to the level of the middle of the trachea ( mtl ) , which was calculated from the tracheal length .\ncc = cricoid cartilage , ett = endotracheal tube , msj = manubriosternal juction , mtl = the level of the middle of the trachea , ssn = suprasternal notch , vc = vocal cord .\nthe correlations between age , height , weight , and tracheal length were analyzed using linear regression .\nthe relationships between surface measurements and the mid - tracheal level were analyzed with bland \nthe distance between the cc and the ssn was longer in females ( p < 0.001 ) , whereas distances between the vc and the cc , the ssn and the carina , and the tracheal length were longer in males ( p < 0.001 ) .\nthe extcc - ssn was longer in females ( p < 0.001 ) , whereas extssn - msj was longer in males ( p < 0.001 ) .\ndemographic data and measured distances between subglottic structures of trachea , external landmarks , and calculated tracheal length .\nthe calculated tracheal length was 131.9 ( 10.3 ) mm and ranged from 106.0 to 169.8 mm .\ntracheal length showed weak correlation with height ( r = 0.2188 ) and weaker correlation with age ( r = 0.0004 ) and weight ( r = 0.0466 ) ( fig .\nthe calculated mid - tracheal level was 66.0 5.1 mm from the vc .\naltman plots showing the difference between the mid - tracheal level and the surface measurements are shown in fig .\nthe bias was calculated by subtracting the mid - tracheal level from the surface measurements .\nthe difference between the extcc - ssn and the mid - tracheal level was 6.6 ( 12.5 ) mm , and the difference between the extssn - msj and the mid - tracheal level was 19.2 ( 6.1 ) mm .\naltman plots showing the agreement between the mid - tracheal level ( mtl ) and the surface measurements of surface anatomical landmarks .\n( left ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 6.6 [ 31.1 to 17.9 ] ( mm ) .\n( right ) the bias ( subtraction of the mid - tracheal level from the surface distance from the suprasternal notch to the manubriosternal junction ) and 95% limit of agreement as the mean difference were 19.2 [ 31.1 to 7.2 ] ( mm ) .\nextcc - ssn = the surface distances from the cricoid cartilage to the suprasternal notch , extssn - msj = the surface distances from the suprasternal notch to the manubriosternal junction , mtl = the level of the middle of the trachea .\naltman plots of the difference between the extcc - ssn and the mid - tracheal level in female and male patients .\nthe calculated mid - tracheal level was 64.5 ( 4.6 ) mm in females and 67.9 ( 5.0 ) mm in males .\nthe difference between the extcc - ssn and the mid - tracheal level was 1.7 ( 11.7 ) mm in females and 12.8 ( 10.7 ) mm in males ( p < 0.001 ) .\naltman plots of female ( left ) and male ( right ) patients showing the agreement between the mid - tracheal level ( mtl ) and the surface the surface distance from the cricoid cartilage from the suprasternal notch .\n( left ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 1.7 [ 24.6 to 21.2 ] ( mm ) in females .\n( right ) the bias ( subtraction of the mid - tracheal level from the surface distance from the cricoid cartilage to the suprasternal notch ) and 95% limit of agreement as the mean difference were 12.8 [ 33.8 to 8.2 ] ( mm ) in males .\nextcc - ssn = the surface distances from the cricoid cartilage to the suprasternal notch , mtl = the level of the middle of the trachea .\nthis study showed that mid - tracheal level could be estimated by the surface distance between the cc and the ssn ( extcc - ssn ) . compared with males , extcc - ssn more\naccurately predicts the mid - tracheal level in females . in clinical practice , physicians can use extcc - ssn to determine the depth of ett so that the segment between the proximal edge of the cuff and the ett tip lies at the mid - tracheal level .\nthere are several studies that used the distance between the surface anatomical landmarks to estimate the airway length and the optimal insertion depth of endotracheal tube .\nlee et al showed that the distance between the upper incisor and the manubriosternal angle in the neck extension position correlates with the distance between the upper incisor and the carina in the neutral neck position .\nevron et al used the sum of the 2 distances from the mouth angle to the jaw angle and from the jaw angle to the sternal manubrium to determine the depth of ett\n. however , these methods are complicated than single measurement of extcc - ssn due to the difficulty in locating the sternal manubrium , more than 1 measurement , and the need for full neck extension .\nthe physicians can easily apply our method with a simple measurement of the extcc - ssn to estimate the mid - tracheal level , and apply this depth during endotracheal intubation .\nhowever , according to previous studies in adults , flexion and extension of the neck from neutral position are associated with the inward and outward movements of the ett .\nconrardy et al showed that the orally intubated ett can move 1.5 ( range 0.52.0 ) cm toward the carina during flexion and 2.4 ( range 1.34.3 ) cm away from the carina during extension .\nkim et al showed that the ett can migrate 1.3 ( sd 0.6 ; range 0.52.5 ) cm toward the carina during flexion and 1.7 ( sd 0.8 ; range 0.43.1 ) cm during extension .\ntherefore , the position of the neck should be considered when determining the optimal depth of the ett .\nfirst , this study was a retrospective analysis of ct images and the distances were measured in the neutral position .\nsecond , since the vc is used as a baseline of the depth of intubation in our method , it can be difficult to apply our method to patients with high cormack grades .\nlastly , the efficacy of this method is yet to be demonstrated in clinical practice . in conclusion ,\nthe mid - tracheal level , which is considered the optimal depth of ett , can be predicted by the surface distance between the cc and ssn in adults , especially in females .", "answer": "abstractendotracheal tube ( ett ) should be placed at the optimal level to avoid single lung ventilation or accidental extubation . \n this study was performed to estimate the mid - tracheal level by using surface anatomical landmarks in adult patients.neck computed tomography images of 329 adult patients between the ages of 16 and 79 years were reviewed . in the midline sagittal plane , the levels corresponding to the vocal cords , cricoid cartilage , suprasternal notch , manubriosternal junction , and carina were identified . \n the surface distances from the cricoid cartilage to the suprasternal notch ( extcc - ssn ) and that from the suprasternal notch to the manubriosternal junction ( extssn - msj ) were measured . \n the relationship between mid - tracheal level and the surface distances was analyzed using bland \n altman plot.the difference between the extcc - ssn and the mid - tracheal level was 6.6 ( 12.5 ) mm , and the difference between the extssn - msj and the mid - tracheal level was 19.2 ( 6.1 ) mm . \n the difference between the extcc - ssn and the mid - tracheal level was smaller in females compared with males [ 1.7 ( 11.7 ) mm vs 12.8 ( 10.7 ) mm ; p < 0.001].the mid - tracheal level , which is helpful in planning the insertion depth of an ett , can be predicted by the surface distance between the cricoid cartilage and suprasternal notch in adults , especially in females .", "id": 394} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan increased incidence of hashimoto thyroiditis has been reported in patients with turner \n syndrome . in view of its pathogenic relationship with autoimmune thyroiditis\nwe report the case of a 9-yr - old girl with turner syndrome who developed graves \n disease during recombinant human gh therapy , and we discuss previous reports of this \n association .\nthe patient was the first child of healthy unrelated parents of normal stature , father \n 175.0 cm and mother 159.0 cm .\nthe patient was born \n after an uncomplicated pregnancy at a gestational age of 37 wks and 1 d. her birth weight \n was 2490 g. on examination , lymphedema and webbed neck were detected .\nchromosomal analysis \n of peripheral blood lymphocytes ( n=26 ) showed complete deletion of the short arm of the \n second x chromosome ( karyotype : 45 , x ) . at the age of 5 yr and 2 mo ,\nher height was 98.2 cm ( 2.25 sd ) and her weight was 14.4 kg \n ( 1.48 sd ) .\na gh stimulation test was performed , and \n the peak gh values after stimulation with clonidine and arginine were 8.39 ng / ml and 5.56 \n ng / ml , respectively . of note\nis that diagnosis of complete gh deficiency is less than 5 \n ng / ml in this assay .\nrecombinant human ( rh ) gh therapy ( 0.175 mg / kg / wk ) was initiated with \n success ( fig .\nthyroid function tests showed a tsh level of 0.01 u / ml ( normal , \n 0.50 to 5.50 u / ml ) , a free ( f ) t4 value of 6.00 ng / dl ( normal , 0.85 to 1.80 \n ng / dl ) , and a free t3 value of 21.76 pg / ml ( normal , 2.50 to 5.50 pg / ml ) . \n\nanti - thyroglobulin antibody was 3.4 u / ml ( normal , < 0.3 u / ml ) .\nanti - thyroid peroxidase \n antibody was 5.5 u / ml ( normal , < 0.3 u / ml ) .\ntsh receptor antibody ( trab ) was 52% ( normal , \n < 15% ) .\nthese results are compatible with a diagnosis of graves disease and treatment \n with thiamazole was started . \ngrowth curve of the patient at the latest follow up ( 9 y old ) , the development of the patient s breast was tanner stage \n 1 .\ntreatment with thiamazole was continued and the thyroid function has stayed within normal \n ranges .\nthe association of turner syndrome with graves disease was reported in english about \n 1020 years ago ( 1,2,3,4,5,6,7,8,9,10 ) .\ntable 1table 1 graves disease in turner syndrome summarizes the historical thirteen known cases of graves disease with turner \n syndrome , including our case .\nthis table reveals that the clinical characteristics of \n graves disease with turner syndrome are similar to those known generally in patients \n without turner syndrome in terms of ages of the onset , symptoms and prognosis .\ntreatment with rhgh was \n given to 4 patients in table 1 , and it was \n continued in 3 out of the 4 patients including our case .\nthis continuation of gh treatment , \n together with the successful treatment of hyperthyroidism , suggests that a direct link \n between gh treatment and graves disease is unlikely .\nconsistent with this hypothesis , the \n incidence of hyperthyroidism in japanese patients with turner syndrome receiving rhgh \n therapy is 0.40% , which is similar to overall incidence of hyperthyroidism in patients with \n turner syndrome , 00.5% ( 11 , 12 ) .\nit is well known that hyperthyroidism in patients with turner syndrome leads to \n acceleration of height velocity ( 6 , 13 ) . in our patient ,\nthe height velocity was not \n increased by hyperthyroidism , probably because her growth had been already accelerated by \n rhgh therapy before the onset of hyperthyroidism .\nit is important to monitor changes of thyroid function as well as growth parameters in \n patients with turner syndrome , as is recommended by sybert and mccauley ( 14 ) .", "answer": "an increased incidence of hashimoto thyroiditis has been reported in patients with \n turner syndrome , but several cases of graves disease were also described ten to 20 years \n ago . \n we report the case of a patient with turner syndrome who developed graves disease , \n 3 years after successful treatment with recombinant human growth hormone ( gh ) . \n a diagnosis \n of graves disease was made and treatment with thiamazole was started , which resulted in \n normalization of the thyroid function . \n it is important to monitor thyroid function as well \n as growth parameters in patients with turner syndrome .", "id": 395} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmost patients are asymptomatic or suffer from mild symptoms only , ( 1 ) and many present with extraintestinal manifestations such as neurologic disorders ( 2 ) .\nthe anti - tissue transglutaminase antibody ( ttga ) test is a sensitive and specific tool in disclosing celiac disease with overt villous atrophy ( 3 ) with a specificity of approximately 95% , false positive tests are uncommon , and ttga may appear in serum at an early stage in the disease , in other words before the clinical manifestations and even before the development of villous atrophy ( 4 ) .\npsychiatric disorders are also common in untreated celiac disease , especially depressive symptoms ( 58 ) .\nhallert & derefeldt reported that nine out of 42 studied subjects had attended a psychiatric clinic because of neurotic problems and most of them are involved with depressive disorders ( 7 ) .\nceliac disease was considered relatively uncommon in iran , until recently an estimated population prevalence of 1:166 was reported ( 9 ) .\ngreater awareness of its varying presentation and the availability of new serologic tests have shown celiac disease to be relatively common ( 10 ) .\nthese observations prompted us now to assess the association between celiac disease and severe chronic depression and schizophrenia .\nthis cross - sectional study was carried out in 2006 - 2007 . by random sampling\n, 200 inpatient men comprising 100 with chronic depression and 100 with schizophrenia ( mean age 37 years , range 18 - 68 years ) were enrolled in razi hospital , tabriz , iran .\nchronic depression was defined according to dsm - iv criteria , ( 11 ) diagnosed and treated by semi - structural clinical interview by two psychiatric experts .\nthe duration of the diseases was more than two years , and the diseases were unbearable without antipsychotic drugs .\npatients with schizophrenia suffered from different types of the disease such as paranoid , phrenetic or undistinguished .\ntwo hundred healthy males were selected as controls , matched for age and birthplace ( mean age 32 , range 4 - 77 years ) .\na written informed consent was obtained from patients ( or from next of kin if necessary ) and the study was approved by the institutional ethics committees of the research center for gastroenterology and liver disease , tabriz medical university .\niga class ttga antibody was measured by enzyme - linked immunosorbent assay using a commercially available kit ( eu - ttg iga , eurospital , trieste , italy ) .\na titer of > 7 u / ml was considered positive as recommended by the manufacturer .\na frequency of 0.6% celiac disease has been reported in iran ( 9 ) . assuming this frequency in 200 controls and a tenfold frequency in psychiatric patients ( 6% , as has been reported in many autoimmune conditions ) the statistical power of 0.80 at a significance level of 0.05\npercentages were compared by rates and proportion ; 95% confidence intervals ( ci ) were reported .\na frequency of 0.6% celiac disease has been reported in iran ( 9 ) . assuming this frequency in 200 controls and a tenfold frequency in psychiatric patients ( 6% , as has been reported in many autoimmune conditions ) the statistical power of 0.80 at a significance level of 0.05\npercentages were compared by rates and proportion ; 95% confidence intervals ( ci ) were reported .\nnone of the 200 patients had a history of chronic diarrhea and all were taking antipsychiatric drugs ( antipsychotic such as risperidone , haloperidol or perphenazine and anticholinegic for schizophrenic patients , and fluoxetine and tricyclic antidepressants for depressive patients ) .\nthree patients with chronic psychiatric disorders were ttga positive , in which one ( age 52 years ) with schizophrenia and two ( both 30 years of age ) with chronic depression . of these three patients ,\ntwo refused duodenal biopsy and one died during the study period . in the control group ,\none ( age 25 years ) out of 200 individuals was positive , but duodenal histology proved normal .\nthe prevalence of positive celiac disease serology in patients with chronic psychiatric disorders was thus slightly but not significantly higher than in controls ; 1.5% , ( 95% ci : 0.38 - 4.03 ) and 0.5% ( 95% ci : 0.00025 - 2.44 ) , respectively ( p = 0.06 ) . clinical features and laboratory findings among the patients with schizophrenia and depression are shown in table 1 .\nfive in the study group and none in the control group had selective iga deficiency . \n \nclinical and laboratory features of male patients with schizophrenia and depression \n ttga iga - class anti - tissue transglutaminase antibody ; meanstandard deviation\nin our reports , the frequency of positive celiac disease serology in iranian inpatients suffering from depression or schizophrenia was 1.5% . by comparison , pynnnen et al .\nhave shown the prevalence of celiac disease in patients with depression to be 0.7% ( 5 ) .\nthe same authors have reported that in adolescent celiac disease patients the frequency of depression and disruptive behavioral disorders was higher than in controls , 31% and 7% , respectively ( 6 ) .\nthe present observations support earlier findings that celiac disease is not increased in patients with schizophrenia .\n( 12 ) studied 7754 schizophrenia patients in denmark and found a frequency of untreated celiac disease of 0.05% . in uk , west et al . showed that in subjects with celiac disease the prevalence of schizophrenia was 0.25% , the adjusted odds ratios showing no association between the two conditions ( celiac disease vs. controls 0.76 , 95% ci : 0.41 - 1.4 ) ( 13 ) .\nby contrast , a study in the uk revealed that patients with celiac disease developed schizophrenia 3 times more frequently than non - celiac controls ( 14 ) .\nsome studies have suggested that schizophrenia and celiac disease may be associated with similar or adjacent genes ( 15 , 16 ) .\nit has indeed been reported that genetic susceptibility in schizophrenia lies in human leukocyte antigen ( hla ) dq , similarly to autoimmune disorders such as celiac disease ( 17 ) .\nby contrast , a recent study showed no such hla association in schizophrenia ( 18 ) . in a case report\n, the symptoms of schizophrenia were improved in a celiac patient aged 33 years after the introduction of gluten free diet ( 19 ) .\nhere we had no opportunity to investigate the effect of gluten - free diet , since two patients refused and one died during the study . in this present study ,\nthe frequency of positive celiac disease serology in patients with chronic depressive ( 2% ) and schizophrenia ( 1% ) was in fact similar to that found in healthy blood donors in iran ( 0.6% ) ( 9 ) . in the latter study ,\nthe frequency of celiac disease in males ( 1.8% ) was higher than in females ( 0.5% ) , although usually 60%-70% of celiac disease patients are female . we could not investigate females with psychiatric disorders , which may be considered as a limitation to the current study . on the other hand ,\nall our patients were inpatients , indicating that they suffered from severe manifestations of chronic psychiatric disorders .\npatients with selective iga deficiency remain negative by ttga iga class screening , and we had no opportunity to test our 5 such subjects by igg class ttga . in blood donors\nthere may thus be additional celiac case in our study group , but we consider that this would not change our conclusions . to conclude , mass screening for celiac disease in patients with depression or schizophrenia is not advocated . despite this , alertness to celiac disease should be high , since early diagnosis and treatment by gluten - free diet may ameliorate the symptoms and quality of life of these patients .", "answer": "aimthe aim of this study was to determine the prevalence of celiac disease in iranian patients suffering from chronic depression or schizophrenia.backgroundpsychiatric disorders are common in untreated celiac disease.patients and methodstwo hundred iranian inpatient men with in chronic phase of depressive disorders or schizophrenia , and 200 age - matched healthy male subjects were screened for celiac disease by anti - tissue transglutaminase iga antibodies . \n the mean age of the study patients was 37 years.resultsone ( 1% ) schizophrenic and two ( 2% ) depressive patients were positive for anti - tissue transglutaminase iga antibodies ; duodenal biopsy was not possible in these subjects . in the control group one ( 0.5% ) \n individual was positive for anti - tissue transglutaminase iga antibodies , but had normal duodenal histology . \n the difference between patients and controls was not statistically significant.conclusionthe frequency of celiac disease serology in schizophrenic and depressive inpatients was not significantly higher than that in the general population \n . we would therefore not advocate systematic serologic screening in these patients , but alertness to celiac disease should be kept in mind .", "id": 396} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nobesity is associated with numerous chronic diseases and , currently , its prevalence is 34% in us adults . \nexcess fat storage is the result of greater energy intake than expenditure for a period of time ; thus , increasing energy expenditure is an important strategy to treat obesity . \nphysical activity energy expenditure ( paee ) can be further divided into energy expended during structured exercise and during activities of daily living other than structured exercise .\nthere has been extensive research investigating the effects of various exercise and/or caloric restriction interventions for inducing weight loss . in general ,\nthese programs are successful at inducing weight loss ; however , there is some evidence showing that increases in total daily energy expenditure during prescribed exercise interventions are less than expected given the amount of energy expended during the prescribed exercise sessions [ 38 ] . \nin support of this , one study showed that accelerometer counts from physical activities outside of structured exercise decreased by 8% after a 12-week training period . \nthis suggests that paee outside of the structured exercise may decrease as a result of the exercise treatment .\nall of these prior studies examined the chronic or longer - term effects of exercise interventions on paee . \nhowever , it is also important to determine whether there are potential changes in paee acutely on days in which the exercise is performed . \nyet , to date , only one small study examined this acute effect of exercise on daily paee . \nit reported that accelerometer counts from nonexercise activities were lower on days with , than without , structured exercise during a 12-week exercise program . \nthus , the purpose of the present study was to determine whether performing a single exercise bout impacts daily paee in postmenopausal women and to determine whether the intensity of the exercise bout plays a role in any potential changes in daily paee .\nwomen in this study are a subset of those enrolled in a randomized clinical trial that was designed to determine whether intensity of aerobic exercise affects the loss of abdominal adipose tissue and improvement in cardiovascular disease risk factors in postmenopausal women with abdominal obesity ( clinicaltrials.gov : nct00664729 ) . \nbriefly , they were : ( 1 ) older postmenopausal ( age : 5070 yr ) , ( 2 ) overweight or obese ( bmi : 2540 kgm and waist circumference > 88 cm ) , ( 3 ) nonsmoking , ( 4 ) not on hormone therapy , and ( 5 ) sedentary ( < 15 minutes of exercise , two times per wk ) in the past 6 months before enrollment . \nthe study was approved by the wake forest university institutional review board , and all women signed an informed consent form to participate in the study according to the guidelines for human research .\ndata used for the current analyses are from women who were randomized to caloric restriction plus moderate - intensity aerobic exercise ( moderate - intensity ) or caloric restriction plus vigorous - intensity aerobic exercise ( vigorous - intensity ) and completed the study interventions . \nthere were 18 women in the moderate - intensity and 18 women in the vigorous - intensity groups who had paee data available from before the intervention and from days with and without center - based exercise in the last month of intervention .\nboth the moderate - intensity and vigorous - intensity interventions were 5 months , and the energy deficit was designed to be approximately 2100 kcalwk from caloric restriction and 700 kcalwk from center - based exercise . \nindividual energy needs for weight maintenance were calculated from each woman 's resting metabolic rate ( indirect calorimetry after an overnight fast by using a medgraphics ccm / d cart and breeze 6.2 software , medgraphics , st .\npaul , mn ) and an activity factor based on self - reported daily activity ( 1.2 - 1.3 for sedentary lifestyle ) .\nindividual diets were developed by a registered dietitian according to each woman 's choices from a menu designed by a registered dietitian . throughout the course of the 5-month intervention ,\nall women were provided with daily lunch , dinner , and snacks prepared by the general clinical research center ( gcrc ) metabolic kitchen . \nthey were asked to eat only the food that was given to them or that was approved from the breakfast menu . \nenergy make - up of the diet was approximately 25% from fat , 15% from protein , and 60% from carbohydrate . \nwomen were allowed to consume as many noncaloric , noncaffeinated beverages as they liked . \nthey were also allowed 2 free days per month during which they were not provided food but were given guidelines for diet intake at their prescribed energy level . \nall women were provided with daily calcium supplements ( 500 mg , 2 timesd ) . \nthey were asked to keep a log of all foods consumed , and the records were monitored by the dietitian to verify compliance .\nthe exercise interventions were center - based walking on treadmills ( lifefitness 9500hr , life fitness co. , il ) on 3 dwk under the supervision of an exercise physiologist . \nexercise progressed from 2025 min the first week to 55 minutes by the end of the sixth week for the moderate - intensity ( 4550% of maximum oxygen consumption , vo2max ) group and it progressed from 1015 minutes the first week to 30 min by the end of the sixth week for the vigorous - intensity ( 7075% of vo2max ) group . \nthe target exercise intensity was determined based on each woman 's target heart rate calculated from the karvonen equation [ ( hrr intensity ) + resting heart rate ] , where hrr is the maximal heart rate , obtained from each woman 's maximum exercise test , minus resting heart rate . \ntreadmill speed and grade were adjusted on an individual basis to ensure women exercised at their prescribed exercise intensity . \nheart rate readings ( by polar heart rate monitors ; polar electro inc , lake success , ny ) were taken before , at least 2 times during ( to monitor compliance to the prescribed exercise intensity ) , and after the exercise .\nit is about the size of a pager and is worn by clipping onto the waist . \nit collects 3-dimensional data at one minute intervals and stores such data for 7 days . \nactivity energy expenditure was computed using the manufacturer 's software from the integrated acceleration and body mass with formula developed by the manufacturer . \ndaily paee was calculated using the average calories expended per minute times 1440 minutes a day .\nwomen were asked to wear the accelerometer before and each month during the intervention , for 57 days including week days and weekend days . \nwomen were instructed not to change their activities while wearing the accelerometer at all times , except while sleeping and bathing . \ndata collected from rt3 monitors were included only when there were valid data from both before the intervention and during the last month of intervention . during the last month of intervention ,\nrt3 data were considered valid when data were collected from at least 2 days with center - based exercise and at least 2 days without center - based exercise . \nthe average paee from days with and without center - based exercise were used for the current analyses . of note ,\nthe average daily paee from days with center - based exercise included the energy expended during the exercise sessions , and none of the women performed structured exercise at baseline .\ntreadmill readings during the exercise sessions were recorded for each woman as a measure of energy expended during center - based exercise . \nheight and weight were measured before and after the 5-month intervention with shoes and jackets or outer garments removed .\nall analyses were performed using sas software , version 9.1 ( sas institute , cary , nc ) . \npaired t - tests were used to compare values within the same group at different measurement points . \nas shown in table 1 , there were no differences in baseline characteristics such as age , racial distribution , body weight , and body mass index between the moderate - intensity and vigorous - intensity groups . \nthe total amount of weight loss during intervention was similar between the moderate - intensity and vigorous - intensity groups ( 12.9 4.2 kg or 14.6 4.8% and 12.6 5.1 kg or 13.5 4.6% , resp . ) . during the last month of intervention ,\npaee on days with center - based exercise was significantly higher in women performing moderate - intensity exercise than in women performing vigorous - intensity exercise ( p = .052 ) . \nin contrast , paee on days without exercise was not statistically different between the two groups ( p = .135 ) .\nin the moderate - intensity group , 13 of the 18 women had higher paee on days with than without center - based exercise ( figure 1 ) , and the average paee on days with exercise ( 577.7 219.7 kcald ) was higher than on days without exercise ( 450.7 140.5 kcald , p = .011 ) ( table 1 ) . yet , the difference ( 127.0 188.1 kcald ) was much smaller than the energy expended during exercise ( 325.0 79.6 kcald ) ( figure 2 ) , suggesting that , during the 5th month of exercise training , women expended less energy on activities outside of the structured exercise when they exercised during the day . in support of this , paee on days with center - based exercise was not different from baseline paee ( 520.8 206.5 kcald ; p > .05 for both ) in women performing moderate - intensity exercise even though energy expended during exercise was included in the daily paee on days with exercise . on the other hand , in the vigorous - intensity group , 12 of the 18 women had lower paee on days with than without center - based exercise during the last month of the intervention ( figure 1 ) . \nthe average daily paee on days with exercise ( 450.6 153.6 kcald ) was lower than on days without exercise ( 519.2 127.4 kcald ) ( difference = 68.6 136.1 kcald , p = .047 ) again even though energy expended during exercise ( 296.8 93.0 kcald ) was included in daily paee on days with exercise ( figure 2 ) . \nthis indicates that , during the 5th month of exercise training , women performing vigorous - intensity exercise were expending more total calories on nonexercise days than on exercise days . \nin addition , paee on days without exercise was not different from baseline daily paee ( 543.2 164.0 kcald ; p > .05 ) ; however , paee on days with exercise ( which included energy expended during center - based exercise ) was significantly lower than baseline paee ( p = .020 ) .\nthis study adds information to the literature regarding how acute exercise sessions affect daily paee and whether the intensity of exercise influences the effects . \nwe found that , during the last month of a 5-month moderate - intensity exercise training intervention , the daily paee during days with center - based exercise was higher than days without exercise by an amount much smaller than the exercise energy expenditure . \nduring the 5th month of a vigorous - intensity exercise training intervention , daily paee during days with center - based exercise was lower than days without center - based exercise sessions , even with energy expended during the exercise sessions included in paee . \ntherefore , there was a reduction in paee outside of the center - based exercise sessions in both intervention groups , and this reduction appeared to differ based on the intensity level of the center - based exercise because it was greater in women performing vigorous - intensity , compared to moderate - intensity , exercise .\nour findings are in line with those of meijer et al . , who found that accelerometer counts of total physical activity were similar between days with and without training , and that after energy expenditure during the training session was subtracted out , accelerometer counts were significantly lower on training days . in their study ,\nthe training program included one aerobic exercise of 60 minutes and one cardio- and weight - stack machine exercise of 90 minutes each week for 12 weeks in men and women of 55 years and older . \nwe can not directly compare the magnitude of the paee responses in our study to their study because the intensity of the exercises was not specified and only accelerometer counts were reported in their study .\nwe also showed that exercise at vigorous intensity induced greater compensation in paee than moderate - intensity exercise . of note ,\nboth exercise programs in our study are consistent with the current physical activity guidelines for adults [ 11 , 12 ] . \nthe frequency of the exercise sessions was the same for the moderate - intensity and vigorous - intensity exercise groups , and the volume of exercise was also similar . \nhowever , this does not exclude the possibility that volume or frequency of exercise of an exercise program may affect the chronic response in paee to the program . \nfurther studies are needed to address these questions because these are important factors to consider when designing exercise programs to better meet an individual 's goal for participating exercise . in this study ,\nthus , women were relatively trained so that paee responses to acute exercise may be somewhat different from those if women were untrained\n. however , we suspect that the compensation in paee is likely lower in the trained state . in other words , for a person who does not participate in regular exercise , an acute session of exercise may induce greater compensation in paee\n. on the other hand , the information found in this study may be more important because with the epidemic of obesity , many individuals participating in exercise programs may think that would satisfy the goal of weight control . \nthus , we should educate and encourage them to maintain higher daily activities while participating in exercise programs at the same time .\nthe results of this study should be interpreted in light of a few considerations . \nthe daily paee during days with and without center - based exercises was the average of at least two days . \nalthough this provides a good measure of activity energy expenditure , it would be better if data from more days were available . \nsecond , all exercise sessions were during the week . for paee during days without exercise , we did not have enough data to determine whether there was a difference in paee between those weekdays and weekend days . \nthese are not accurate measures of energy expenditure ; however , we believe this will not affect our conclusion given the big difference shown between exercise energy expenditure and the difference between paee during days with and without exercise sessions ( figure 2 ) . in summary ,\nthe main finding of this study is that women expended more energy during physical activities outside of prescribed exercise sessions on days they did not perform center - based exercise , especially if the prescribed exercise was of a higher intensity . \nmore research is needed to determine what exercise prescription can minimize this compensation . \nthis phenomenon may have biological and behavioral reasons , and future research investigating the underlying mechanisms is warranted . \nthus , health professionals should encourage individuals who are participating in exercise programs to maintain levels of activity in addition to the program , so that greater weight loss can be achieved .", "answer": "this study determined whether performing a single moderate- or vigorous - intensity exercise bout impacts daily physical activity energy expenditure ( paee , by accelerometer ) . \n overweight / obese postmenopausal women underwent a 5-month caloric restriction and moderate- ( n = 18 ) or vigorous - intensity ( n = 18 ) center - based aerobic exercise intervention . during the last month of intervention , in women performing moderate - intensity exercise , paee on days with exercise ( 577.7 219.7 kcald1 ) was higher ( p = .011 ) than on days without exercise ( 450.7 140.5 kcald1 ) ; however , the difference ( 127.0 188.1 kcald1 ) was much lower than the energy expended during exercise . in \n women performing vigorous - intensity exercise , paee on days with exercise ( 450.6 153.6 kcald1 ) was lower ( p = .047 ) than on days without exercise ( 519.2 127.4 kcald1 ) . \n thus , women expended more energy on physical activities outside of prescribed exercise on days they did not perform center - based exercise , especially if the prescribed exercise was of a higher intensity .", "id": 397} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe nerves and their structures change and are subject to the law of neuroplasticity : they adapt to reflect the stimulus which is present ( mechanical , biochemical , electrical , or metabolic).1 the peripheral nervous system is subjected to a daily mechanical tensile load , as when a joint moves , undergoing compression and stretching .\ncompression happens when the surrounding tissues create a longitudinal force to a nerve , such as when the muscles are stretched , while stretching occurs when a force is parallel to the nerve , for example , when the elbow is flexed , the ulnar nerve is stretched.2 this mechanical stress can leave the physiological confines when there is direct trauma to the nerve or surrounding tissue.2 the physiological tensile load allows the nerve to regenerate , through autocrine and paracrine substances , generated by the same nervous structure . when the nerve is subjected to stress in elongation , the schwann cells can proliferate and synthesize many neurotrophic factors , which play roles in nerve repair and remodeling.3 the synthesized molecules are varied , with different functions depending on the site of production and the quantity and based on the combinations that occur ; their direction and propulsion force also change.4,5 the synthesized molecules from nerve structure can travel along the nerve and stimulate the various receptors , activating or switching them off , so as to or not to interact with the molecule produced ; the same molecules can behave in different modes based on the area where they were synthe - sized.4,5 in order for the nervous tissue to reshape correctly , it must have the ability to retain its elasticity .\nthe correct sliding of the fascial structures that make up nerves and the sliding of nerves between the various tissues that cross and innervate it become fundamental , so that the mechanical stress can be communicated properly and has the ability to adapt and regenerate the nerves.6 an impediment to this slide will lead to dysfunction and pathology.7 the biochemical information carried by the nerve does not merely have the function of operating on the nervous system , but it is also able to assist trophism and tissue function that crosses the nerve and innervates it .\nnerves can carry multipotent cells for repair and remodeling of tissues and organs , which are innervated by the same nerves.8 the fascial structure of a nerve is divided into three layers : the endoneurium , perineurium , and epineurium .\nall the layers are innervated and have a subtle but potentially important plexus of nociceptors.9 the epineurium is composed mainly of type i and iii collagen , fibroblasts , mast cells , and fat cells .\nthe inter - fascial epineurium is loosely attached to the perineurium , facilitating sliding of the various fascia .\nthere is abundant epineurium in larger nerves , in order to disperse most of the compressive forces .\nthe epineurium is attached to paraneural fascial components of the connective tissue that surrounds the nerve and is an extension of the dura mater .\nthe vessels enter the epineurium in rolled - up form ( to adapt better to the strain in elongation of the nerve ) and periodically along its length , forming the vasa nervorum .\ntherefore , the epineurium supports the blood vessels while keeping the microvascularity of the nerve constant and also supports the nervi nervorum ( sensory nerve fibers ) of the nerve itself .\nit contributes to the tensile strength of the nerve and to the sliding , but it does not provide a barrier function.10,11 the perineurium surrounds the axon filaments with a dense connective tissue and the same perinerium is formed by up to 15 layers of flat perineural cells .\nwe can encounter collagen type i and ii , and other cells with different carriers modulating the tension recorded from the nerve , thereby regulating intraneural pressure .\nperineural cells synthesize several substances and are in close contact with laminin and collagen type iv , further acting as a shock absorber .\nanother key task of the perineurium is to act as a blood barrier , ie , not allowing all the filtered substances to reach the endoneurium .\narterioles that reach and penetrate the perineurium form an oblique angle ; these vessels have developed little smooth muscle and therefore do not possess a great intrinsic ability to regulate blood flow .\nnevertheless , the perineurium performs important functions in the repair of nerve tissue by managing the traffic of molecules inside and out of the neural environment by active transcytotic transport.10,11 a study has shown the presence of many pinocytotic vesicles for this transcytosis , but more research is needed to draw conclusions.11 molecules can also be transported via specific membrane receptors.11 the endoneurium contains individual axons wrapped several times by schwann cells ; this sheet is in turn wrapped by type iv collagen cells , fibronectin , laminin , and proteoglycans . inserted between the various filaments , collagen type i and ii with a longitudinal orientation ,\nmast cells and macrophages , and endoneurial fluid ( 70% water ) can be found .\nthe capillaries that penetrate the endoneurium increase in size , allowing the blood flow to head in different directions .\nthe arterioles , however , are tightly wrapped by the endoneurium cells to create an additional barrier to the blood .\nit is most likely that the blood flow comes into contact with the endoneurium by diffusion .\nvenules carry the blood back to the venous system . the lymphatic system , however ,\nis present only in the epineurium ; there are no lymphatic drainage vessels into the nerves ( figure 1).10,11 the nervi nervorum , or a nerve s nerves , can evoke local neuroinflammation when there is nonphysiological damage or mechanical stress to the nerve tissue , to assist in its repair.9 the fascial nerve system innervated by the nervi nervorum may become a source of local pain.9 another cause of pain by the fascial nerve system , connected to axonal and physiological dysfunctions and capable of generating dysesthetic or distant pain ( for example , pain resulting from traction of the sciatic nerve , when the leg is stretched during tests ) , follows directly from the fascial structures of the axon .\nthese fascial structures become more sensitive to mechanical stimulation and , after a few days of local inflammation , they are able to generate potential action similar to the mechanical stimulus that causes dysfunction .\nthis mechanism is known as ectopic electrogen - esis.9 such nonphysiological situations may require from 1 week to 2 months to disappear and only involve the epineurium and perineurium.9 there is a strong hypothesis that impeded sliding of a nerve between its various layers and tissues that cross its fascial system will generate local and dysesthetic pain .\nwhen there is an impediment to the sliding of a nerve , the rigidity of its fascial structures during joint movement is increased , and this is even more true when the joint is moved swiftly , which often occurs with everyday gestures.10 an elongated nerve causes a reduction in its diameter , defined as transverse contraction , with an increase in the pressure of the endoneurial compartment.10 its return to size and length at rest happens due to the elasticity of the perineural tissue , while the endoneurial tissue has less elastic compliance.10 a decrease in the nerve s ability to stretch may damage the endoneurial integrity before a lesion to the epineurium is visible.10 repetitive elongation of a nerve with reduced fascial elasticity properties brings about further inability of the nerve to slide , decreasing blood flow and likely leading to ischemic problems.10 for example , use of a computer mouse for prolonged periods leads to a reduction of the flow capacity of the median nerve at the level of the carpal tunnel , with possible pathological consequences of nerve compression , including the formation of edema , inflammation , and the production of adhesions , along with pain and reduced axonal flow ( figure 2).10 edema is found at the intraneural level and is a common response to trauma , compression , tension , or excessive vibration .\na slight trauma may give rise to edema , more superficially , at the epineural level ; this can be transformed into intraneural edema if compression continues , creating a mini - compartmental syndrome of the nerve , due also to the absence of lymphatic vessels in the endoneurium .\nall this will lead to fibrous adhesions , decreasing the sliding of the intrafascicular tissue .\nthe fibrosis increases the compression both inside and outside the tissues with a thickening of the nerve .\nthis is even more noticeable when the nerve passes through small areas.12 the situation described will still generate pain symptoms .\nmany peripheral nerves can be palpated and directly moved , but at the same time , they are more susceptible to trauma than the central nervous system , which is protected by the cranium.9,13 many peripheral nerves can be palpated and directly moved for anatomical reasons.9\nthere are very few texts in the scientific literature on manual treatment of the peripheral nervous system .\nsuch therapy is used by manual operators with the intent of allowing adequate sliding of the peripheral nerve and surrounding tissue , using two methods in particular : the sliding technique or a technique that alters the tension of the nerve path.13 studies on the human model are scarce , and there are no precise data on the method of movement that should be performed on a patient s nerve path in order to optimize the results .\nspecific work protocols are lacking , and a positive clinic outcome is not always observed.1419 within the field of osteopathy , there are no scientific articles that deal with palpation or manual techniques applied directly to the peripheral nerve , although there is a book that describes and shows how the osteopathic operator should palpate and treat emergencies superficial to the nerve path.20 the purpose of these therapies and treatments is to alter the mechanical properties of fascia , such as density , stiffness , and viscosity , so that the fascia can more readily adapt to physical stresses .\nin fact , some osteopathic physicians and manual therapists report local tissue release after the application of a slow manual force to tight fascial areas ; these reports have been explained as a breaking of fascial cross - links , a transition from gel to sol state in the extracellular matrix , and other passive viscoelastic changes of fasciae.21 the fascial osteopathic technique is the application of a low - load , long - duration stretch into the myofascial complex that is intended to restore the optimal length of this complex.21 the operator places his or her hand on the fascial restriction identified previously by palpation , using different approaches , until the perceived resistance disappears or greatly decreases , inducing or stopping the preferential direction of the tissue.21,22 the time required for the technique varies according to the response of the patient.22 there are reports in the literature that improvement in the sliding of the different fascia layers , via manual manipulation , may decrease pain symptoms and reduce inflammation at the local level.21,23 palpation of the peripheral nerves is feasible and is also used to evaluate nerve function , because these nerves are very often superficial.24,25 our clinical experience encourages us to support osteopathic fascial treatment of the peripheral nerve , providing a strong incentive to launch new research aimed at understanding what happens to the nerve using fascial osteopathic techniques , in addition to quantifying the benefit derived by the patient .\nit is important to remember that evidence - based medicine involves not only scientific research highlighted in an article , but also the patient s experience of treatment and the clinical experience of the operator.26 to provide some examples of treatment of peripheral nerve fascia , a finger or fingers are placed on the nerve emergence , either at the elbow on the cubital tunnel , where it passes the ulnar nerve ( figure 3 ) , or in the middle third lateral of the humerus , where the radial nerve passes ( figure 4).24 ulnar compression difficulties may be encountered at the cubital tunnel level , while the humeral area is subject to direct trauma that might damage the radial nerve.2729 the method of treating any emergence of the peripheral nerve is relatively simple and noninvasive .\nonce the fingers are in contact with the emergence and the most superficial area of the nerve branches , a fascial osteopathic technique is used , during which the operator waits for the tissues of the fabric to release under the fingers.21 it is common for the area being treated to be characterized by tissue hardness , with layers that slide with difficulty under the fingers : the technique ends when the tissue in the area has been restored , as close as possible , to a softer , more flexible tissue .\nwe do not know the exact scientific reasons for this fascial release , despite many studies showing that an osteopathic fascial treatment is useful in many clinical conditions.21 an in vitro study demonstrates how osteopathic techniques can influence the metabolic behavior of fibroblasts , such as proliferation and inflammatory response.21 another possible explanation is that improved sliding of the various fascial layers would allow resetting of the afferents of the free nerve endings , resulting in a physiologic response of the efferents.21 further studies are expected in order to facilitate choosing the best osteopathic approach to ensure the well - being of the patient .\nthe peripheral nerves are composed of several layers of fascial tissue , which can become a source of pain if they fail in their ability to slide .\nit is only recently that fascial osteopathy research has been aimed at understanding what happens to the fascia following treatment and , as a result of the first studies , it has been possible to highlight some of the benefits , including a reduction in local pain and inflammation .\nthe osteopathic approach to the fascial system of the peripheral nerve does not have a grounding in scientific research , being based only on the clinical experience of individual operators , despite the use of peripheral nerve palpation as a method for the evaluation and testing of the nerve s function .\nthe authors wish to encourage the initiation of new research in the fields of academic and clinical osteopathy that is aimed at quantifying the possible benefits a patient may derive from osteopathic treatment of the peripheral nerve .", "answer": "the peripheral nerve is composed of several layers of fascia tissue , which can become a source of pain if the way they slide is impeded . \n it is only recently that fascial osteopathy research has been aimed at understanding what happens to the fascia following treatment , and as a result of previous studies , we are able to highlight some of the benefits , including a reduction in local pain and inflammation . the osteopathic approach to the fascial system of the peripheral nerve does not have a grounding in scientific research , being based instead on the clinical experience of individual operators , despite peripheral nerve palpation being used as a method to evaluate and test its function . \n the authors wish to encourage the initiation of new research in the fields of academic and clinical osteopathy that is aimed at quantifying the possible benefits a patient may derive from osteopathic treatment of the peripheral nerve .", "id": 398} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninfarct of the anterior spinal artery is the most common subtype of spinal cord infarct , and is characterized by bilateral motor deficits with spinothalamic sensory deficits .\nwe experienced a case with atypical anterior - spinal - artery infarct that presented with bilateral hand weakness but without sensory deficits .\na 29-year - old man presented with sudden neck pain and bilateral weakness of the hands . magnetic resonance imaging ( mri ) of the brain did not reveal any lesion .\nhis motor symptoms improved rapidly except for mild weakness in his left wrist and fingers .\nmagnetic resonance angiography showed proximal occlusion of the left vertebral artery ; a spine mri revealed left cervical cord infarction .\nbilateral or unilateral hand weakness can be the sole symptom of a cervical cord infarct .\nspinal cord infarction is much less frequent than cerebral infarction , accounting for only 1% of all strokes.1 the anterior spinal artery supplies the anterior two - thirds of the spinal cord via the sulcal ( central ) artery .\nthis usually results in anterior spinal artery infarcts presenting with profound bilateral motor deficits , sensory disturbances , and spinothalamic sensory deficits.2,3 although the mechanisms are not completely understood , there are some case reports of restrictive clinical syndromes , such as the ' man - in - the - barrel syndrome ' and the sulcal artery syndrome.4,5 here we describe a patient who presented with bilateral hand weakness but without sensory deficits due to left vertebral artery occlusion .\na healthy 29-year - old man without any vascular risk factors presented with sudden neck pain and bilateral hand weakness . after flexing his neck while tying his shoelaces\n, the patient experienced a sudden , severe pain ( with a maximum score on a visual analog scale ) that started in the posterior neck and spread rapidly across the entire head .\nbilateral hand weakness that followed the pain onset prevented the patient from tying his shoelaces .\nthe patient 's vital signs were stable upon hospital admission , except for markedly elevated blood pressure ( 202/108 mm hg ) .\nthe initial neurological examination revealed weakness in both flexion and extension of the wrists and fingers bilaterally , and during left leg extension [ medical research council ( mrc ) grade 4 ] .\nhowever , the deep tendon reflexes were normal and the patient denied hypoesthesia in any sensory modality including pain , temperature , proprioception , and vibration .\nlaboratory findings were normal , and chest radiography did not reveal any pathology ; an electrocardiogram also produced no evidence of ischemia or arrhythmia .\nhis motor symptoms improved rapidly within 1 day except for mild weakness of his left wrist ( mrc grade of flexion / extension iv / iv ) and fingers ( mrc grade of flexion / extension iv / iv ; slightly more severe in the 5th finger ) .\nbrain computed tomography ( ct ) and brain magnetic resonance imaging ( mri ) did not reveal any signal abnormalities or mass lesions .\nhowever , ct aortography identified severe stenosis and occlusion of the left vertebral artery , and a pseudo lumen with mural thrombi was suspected on cervical mri ( fig .\nmri of the cervical segment produced high signal intensities in the left gray matter of spinal cord at the c3 , c4 , and c6 levels on diffusion - weighted images ( fig .\nmagnetic resonance angiography performed 3 months after symptom onset showed persistent occlusion of the left vertebral artery .\nunique features of this spinal - cord - infarct patient were bilateral hand weakness , absence of sensory deficits , and rapid improvement of motor symptoms in the right hand and left leg .\nweakness of both arms has been reported previously in association with cervical cord infarcts , typically also with spinothalamic sensory deficit and vertebral artery occlusion.4,5,6,7 the mechanism that preserves leg strength in these cases is most likely collateral flow from the surrounding pial plexus.4 nevertheless , weakness of both hands without sensory deficits is rare in infarcts of the cervical spinal cord , and its mechanism remains to be determined.7,8 the anterior spinal artery forms at the level of the foramen magnum from the branches of the vertebral artery , and gives rise to the sulcal ( central ) arteries that penetrate the right and left sides of the spinal cord.3 unlike circumferential areas of the spinal cord , its interior has no anastomosis and the sulcal arteries are essentially end arteries .\ntherefore , the weakness of both hands in the present patient suggests that the end - arteries zone or the zone bordering the sulcal artery and circumferential artery corresponds to a region where hand motor neurons are located bilaterally.8 this would include the ventrolateral to lateral regions within the gray matter of the lower cervical spinal cord ( fig .\n3).9,10 alternatively , the hand motor areas may be more vulnerable than the more proximal arm motor areas .\nthe hand motor area occupies a relatively large proportion of the cortical homunculus , so the hand motor area may occupy a larger area in the spinal gray matter , or require a larger blood supply.11,12 finally , the isolated unilateral hand weakness of this patient may be related to variation in the branches of the sulcal artery .\nsuccessive sulcal arteries generally alternate in their distribution to the left or right side of the spinal cord , but not both ; this would make unilateral involvement or improvement possible.5 sensory deficit was absent in the present case .\nall subtypes of spinal cord infarcts are presumed to have sensory deficits , and therefore a pure motor presentation can result in misdiagnosis.2,3 anterolateral involvement could explain the present atypical presentation , and bilateral presentation without facial weakness may indicate a spinal cord infarct.5 transient ischemic attacks in the spinal cord reported occur primarily in the cervical cord , and recovery depends on the severity of the initial involvement and its collateral flow.1,2,6 cervical lesions are generally less vulnerable to ischemic insults than are thoracic or lumbar lesions due to the intensive vascularization from the vertebral and radicular arteries.3,6,13 the rapid improvement in the present case might therefore have resulted from initial distal involvement and collateral flow from the intact right vertebral artery . in conclusion , transient bilateral hand weakness can be the initial symptom of a spinal cord infarct , and unilateral hand weakness can be the sole symptom of a cervical cord infarct .", "answer": "backgroundinfarct of the anterior spinal artery is the most common subtype of spinal cord infarct , and is characterized by bilateral motor deficits with spinothalamic sensory deficits . \n we experienced a case with atypical anterior - spinal - artery infarct that presented with bilateral hand weakness but without sensory deficits.case reporta 29-year - old man presented with sudden neck pain and bilateral weakness of the hands . \n magnetic resonance imaging ( mri ) of the brain did not reveal any lesion . \n his motor symptoms improved rapidly except for mild weakness in his left wrist and fingers . \n magnetic resonance angiography showed proximal occlusion of the left vertebral artery ; a spine mri revealed left cervical cord infarction.conclusionsbilateral or unilateral hand weakness can be the sole symptom of a cervical cord infarct .", "id": 399} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nperi - implantitis is inflammation of the peri - implant supporting tissue , which can lead to progressive loss of supporting bone , if untreated .\na history of periodontitis , poor oral hygiene , and smoking are considered risk factors for peri - implant diseases .\nit is of paramount importance to treat periodontitis of the residual dentition prior to implant placement . a higher implant failure rate and elevated number of sites with peri - implant bone loss were documented in periodontally compromised patients who did not adhere to comprehensive supportive periodontal therapy . customized and correctly performed\nsupportive periodontal therapy is essential to enhance the long - term outcome of implant therapy .\nthe outcome of non - surgical periodontal treatment ( nspt ) of peri - implantitis is unpredictable .\nalthough minor beneficial effects of laser therapy on peri - implantitis have been shown , this method requires further evaluation .\nthe diode laser is not an ablative instrument and can directly contact the implant surfaces without inducing melting , cracking , or crater formation .\nthe 810-nm diode laser , when used in accordance with appropriate parameters , does not damage titanium surfaces , which is useful when uncovering submerged implants , and can be used to treat bacterial induced peri - implantitis .\nthe use of laser treatment in periodontal therapy is an emerging therapeutic option , although little reliable evidence suggests that it can effectively treat peri - implantitis .\na 45-year - old male presented with pain and swelling at a mandibular implant site ( nobel biocare , sw ) . clinical examination revealed a deep pocket [ 7-mm pocket depth ( pd ) ] and bleeding on probing [ figure 1 ] , with suppuration and gingival inflammatory edema at the implant site .\nthe patient was in good general health , did not take any medications , and was an occasional smoker ( 4 - 5 cigarettes / day ) .\nclinical examination revealed 7-mm probing depths , circumferentially around a mandibular implant , bleeding on probing , and the presence of exudate and gingival inflammatory edema no occlusal trauma or parafunctional habits were detected .\na periapical radiograph demonstrated bone loss of five fixture threads on the most distal mandibular left implant , when compared to the original radiograph [ figure 2 ] .\nperiapical radiography shows bone loss for five fixture threads on the most distal mandibular left implant the patient was eventually scheduled for periodontal surgery to treat the inflammatory lesion , but emergency intervention was indicated to disinfect the area by removing the bacterial biofilm and alleviating pain using an 810-nm diode laser [ figure 3 ] .\nthe patient was treated using an 810-nm diode laser to disinfect the area and facilitate bacterial biofilm removal by mechanical and manual periodontal instrumentation the patient was asked to rinse with undiluted chlorhexidine 0.2% for 1 min .\nafter insertion of the optical fiber parallel to the long axis of the implant 1 mm from the most apical portion of the pocket , the diode insert was moved in an apico - coronal and mesio - distal direction for 30 sec at each inflamed implant site .\nit was used at a power of 0.5 w in a continuous wave ( cw ) [ equivalent to 1 w in pulsating mode ( pw ) for 30 s ] in duplicate on each site , for a total time of 360 sec with a fluence of 1.96 j / cm .\nnon - surgical periodontal instrumentation was performed with hand instrumentation using a titan curette ( roncati implant care , by martin kls ) and a piezoelectric ultrasonic device with plastic fused to a metal insert ( piezon master 700 , ems , pi insert ) , as needed .\nfinally , a 0.5% chlorhexidine gel was deposited into the sulcus with a disposable syringe and a blunt needle .\nthe area was checked for plaque removal and home care compliance for the first month on a weekly basis and was followed by routine supportive periodontal therapy at 3-month intervals .\nthe adjunctive use of the diode laser was included in the conventional periodontal maintenance every 6 months for the following 3 years .\nperiodontal indices were documented and intraoral periapical radiographs were taken at the 1-year [ figure 4 ] , and 2- , 3- , 4- , and 5-year [ figures 5 and 6 ] follow - up recall appointments .\nperiapical radiograph : 1-year post - non - surgical treatment periapical radiograph : 5-year follow - up clinical probing depth : 5-year follow - up satisfactory results were obtained by the application of laser - assisted non - surgical peri - implant therapy .\nperiodontal pocket depth was reduced from 7 to 3 mm with no bleeding upon probing .\nintraoral periapical radiographs , taken for up to 5 years post - non - surgical treatment , provide evidence of some improvement of the bone level .\nthe reduction of periodontal pockets is probably due to re - epithelialization , with formation of a long junctional epithelial attachment .\nat the 6 european workshop on periodontology , it was reported that mechanical non - surgical therapy with an adjunct of local antibiotics or laser application was effective longitudinally to reduce bleeding on probing and pds over a period of 6 - 12 months .\nhowever , the outcome is unpredictable due to possible re - infection related to the inability to completely remove bacterial deposits from titanium implant surfaces , thus interfering with new histological bone - to - implant contact .\nthe primary objective of non - surgical treatment for peri - implantitis is to remove bacterial contaminants to allow resolution of the inflammatory lesion . to date , no critical probing depths in the therapy of peri - implant diseases have been defined to guide selection of a non - surgical or surgical approach .\nlaser treatment may serve as an alternative or adjunctive treatment to conventional periodontal mechanical therapy or peri - implantitis .\ndiode lasers have a bactericidal effect due to a localized increase in temperature , which has been verified in vivo using dna probes that detect periodontal pathogens .\nthreaded implants have a different morphology than root surfaces ; therefore , debridement instruments might be different .\nthe laser may be a valuable tool to detoxify the implant surface [ figure 7 ] , and significant bacterial reduction should lead to a more satisfactory recovery .\nit is possible to point the diode laser insert toward the wall of the ulcerated pocket epithelium to kill virulent periodontal pathogens .\nvaporization of granulomatous tissue seems to result in a more favorable effect compared to that of solo instrumentation .\nthreaded implants have a different morphology than root surfaces ; therefore , debridement instruments may differ .\nthe laser may facilitate detoxification of the implant surface the diode laser detoxifies root and implant surfaces by inactivating bacterial endotoxins .\nthe thermal effect weakens calculus chemical adhesion to the root and/or implant , facilitating its removal by curette or ultrasonic devices .\nthe diode laser also stimulates fibroblasts and osteoblasts , which , in turn , cause increased production of rna messengers , leading to significant collagen production during periodontal tissue healing .\nthe patient experienced no postoperative discomfort and he was able to comply with home care procedures , such as debridement , after the surgery .\nin contrast , patients often have post - treatment discomfort , and compliance with home care procedures decreases because the recommended home care protocols for plaque control are painful ; this results in impaired healing .\nimportant changes were also detected in the patient : bleeding , a marker of inflammation with a high prognostic value , was compared at baseline and at 1 year after laser - assisted periodontal therapy , and was reduced significantly to < 20% .\nabsence of bleeding has a negative predictive value . besides laser therapy , the following therapeutic interventions\nall of these combined may have contributed to healing , complicating isolation of the most effective modality .\nthe laser has been used as an adjunct to many periodontal treatments , but it is not a replacement for conventional non - surgical treatment or proper home care with adequate patient compliance . the absence of attached gingiva may be an etiological factor in the development of peri - implantitis ; this issue is controversial .\ntraditional protocols of non - surgical periodontal therapy , in conjunction with the use of an 810-nm diode laser , can be an effective alternative treatment modality for peri - implantitis\n. other treatment options may successfully enhance resolution of peri - implant soft and hard tissue inflammation , and preserve long - term periodontal health .\nregardless of the method used , correctly performed supportive periodontal therapy is a key factor in successful implant therapy .", "answer": "an 810-nm diode laser was used to non - surgically treat a 7-mm pocket around an implant that had five threads of bone loss , bop+ , and exudate , and the patient was followed up for 5 years . \n non - surgical treatment , home care reinforcement , clinical indices records , and radiographic examination were completed in two consecutive 1-h appointments within 24 h. the patient was monitored frequently for the first 3 months . \n subsequently , maintenance debridement visits were scheduled at 3-month intervals . \n the patient had a decreased probing pocket depth and a negative bop index compared to initial clinical data , and the results were stable after 1 year . \n after 5 years of follow - up visits , there appeared to be rebound of the bone level radiographically . within the limits of this case report \n , conventional non - surgical periodontal therapy with the adjunctive use of an 810-nm diode laser may be a feasible alternative approach for the management of peri - implantitis . \n the 5-year clinical and radiographic outcomes indicated maintenance of the clinical improvement .", "id": 400} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntopical bimatoprost is a popular prostaglandin analog used primarily as a powerful ocular hypotensive agent for treatment of glaucoma ( approved in 2001 ) .\nit is also used cosmetically to induce hypertrichosis , approved by the us food and drug administration in 2008 as latisse ( allergan , inc , irvine , ca , usa ) .\nhowever , it may cause complications such as periocular skin hyperpigmentation , intraocular inflammation , and conjunctival hyperemia.1 these mainly affect superficial tissues and , to date , there has been no report on involvement of deeper periocular tissues as far as we are aware .\nherein , we report an unusual case of periocular muscle atrophy and weakness secondary to unilateral topical bimatoprost use .\na 58-year - old chinese female was referred to the oculoplastics services of national university hospital , singapore , for right upper eyelid ptosis of 1.5 years duration and difficulty in closing her right eye .\nshe had a history of bilateral primary angle closure diagnosed in 2003 , for which bilateral laser peripheral iridotomies were performed .\nshe was started on topical latanoprost 0.005% once every night to the right eye , as intraocular pressure ( iop ) was suboptimal .\nsubsequently , she underwent an uneventful right cataract extraction with intraocular lens implantation that same year .\nher condition remained stable until 2008 when there were progressive defects in her right visual field with increased iop .\nthus , she was started on topical bimatoprost 0.03% ( lumigan , allergan , inc ) once every night to her right eye .\nhowever , she reported an onset of right upper eyelid drooping 2 months after starting treatment .\nthe ptosis did not show any diurnal variability or fatigability , and there was no diplopia . a detailed evaluation by the neuro - ophthalmology team revealed no underlying neurological cause .\nfour months after starting treatment , the treated eye was found to have long eyelashes and ocular pigmentation .\nsubsequently , the patient reported worsening of her right ptosis after 12 months on treatment and was keen for referral to the oculoplastics team . by the time the patient was reviewed by the oculoplastics team in 2010\nmeasurements of the palpebral aperture ( pa ) of her right and left eye were 6 mm and 8 mm , respectively . measurements of marginal reflex distance 1 ( mrd1 ) for her right and left eyes were 0.5 mm and 2 mm , respectively .\nlevator palpebrae function was 8 mm for the right eye and 14 mm for the left eye .\nlid creases measured 7 mm and 5 mm for the right and left eye , respectively . eventually , the patient underwent a surgical correction of her ptosis with levator muscle advancement in august 2011 .\nseven months after the operation , her pa measured 9 mm and 8 mm while mrd1 measured 4 mm and 3 mm for the right and left eye , respectively . the pre- and postoperative clinical photos of her eyelids are shown in figures 1 and 2 , respectively .\npreoperatively , she had clinically significant right ptosis obscuring her visual axis , and right lagophthalmos with orbicularis oculi muscle weakness .\ntopical bimatoprost is highly efficacious and superior to many other anti - glaucoma eye drops.2,3 however , it commonly causes side effects such as ocular hyperemia , periocular and iris pigmentary changes , although these are mostly reversible with cessation of use.4 periorbital lipodystrophy resulting in periorbital hollowing , eyelid retraction , and enophthalmos from chronic use of bimatoprost has also been well - documented.58 upper eyelid sulcus deepening has been shown to occur significantly more frequently ( objectively and subjectively ) with bimatoprost use than with other prostaglandin analogs , namely latanoprost , tafluprost , and unoprostone.9 aihara et al reported an increased incidence of upper eyelid sulcus deepening in patients who were switched from latanoprost to bimatoprost , suggesting that the latter has a more potent effect on periorbital fat tissue.10 the term prostaglandin - associated periorbitopathy ( pap ) has been coined to describe the constellation of periorbital soft - tissue changes resulting from the use of topical prostaglandin analogs .\nthe clinical features of pap include upper eyelid ptosis , deepening of the upper eyelid sulcus , involution of dermatochalasis , orbital fat atrophy , mild enophthalmos , flattening of lower eyelid bags , inferior scleral show , and tight orbits.11 these effects can appear after a period of several weeks to several years , and have been reported to be reversible upon cessation of use.11 most of the anatomical changes in pap are thought to be caused by orbital fat atrophy , while dehiscence of levator aponeurosis or mller muscle may account for the upper lid ptosis.11 it has been postulated that upregulation of prostaglandin f2- results in significant anti - adipogenic effect.12 prostaglandin f2- blocks adipogenesis through the activation of mitogen - activated protein kinase , resulting in the inhibitory phosphorylation of peroxisome proliferator - activated receptor - gamma , a nuclear hormone receptor central to adipocyte differentiation.13,14 topical prostaglandin analogs have been shown to downregulate the expression of peroxisome proliferator - activated receptor - gamma and inhibit the accumulation of intracytoplasmic lipid droplets.15 the reversal of fat atrophy upon cessation of use may be due to removal of this inhibition , allowing adipogenesis to recommence .\nimaging of orbits ( computed tomography and magnetic resonance imaging ) has ruled out orbital pathology in the fellow eye ( resulting in pseudo - enophthalmos ) and other disease processes such as cicatrizing changes.5,6 periorbital changes may be underestimated , as they may be subtle or attributed to age - related volume depletion .\nbilateral topical use of prostaglandin analog eye drops in glaucoma may lead to equivocal changes in both eyes , which may be less obvious and thus under - reported .\nhowever , in asians , who tend to have greater upper eyelid fullness , unilateral periorbital fat atrophy may result in more obvious disfigurement.16 to date , as far as we are aware , there has been no report of topical bimatoprost use resulting in periorbital muscle atrophy .\nin figure 1 , it can also be seen that the patient had deepening of her upper eyelid sulcus and dermatochalasis involution .\nclinical eyelid measurements clearly showed reduced function of the right upper eyelid , suggesting that the effects of topical bimatoprost may not be limited to periorbital fat .\nreduced levator function and ptosis may be masked by the more common eyelid retraction and deepening of the upper eyelid sulcus .\npeplinski and albiani smith postulated that mller muscle ( smooth muscle ) may be directly affected by prostaglandin - mediated pathways , but whether there is a similar effect on levator muscle ( striated muscle ) remains unknown.17 other reasons for the induced right ptosis might have been stretching of the eyelid due to initiation of glaucoma - drop usage , disruption of the whitnall s suspensory ligament from the relative enophthalmos , or the patient s previous cataract surgery , even though there was no fixing of patient s superior rectus during the surgery .\nfurther studies are warranted . in this case , the patient was advised to stop topical bimatoprost and right ptosis correction surgery was performed successfully . in figure 2 , it can be seen that the upper eyelid sulcus deepening was much reduced , with a marked improvement in the dermatochalasis involution after the surgery .\nit may be worthwhile to note that topical bimatoprost used cosmetically can also cause unwanted side effects such as conjunctival hyperemia and iop reduction.18 therefore , while considered generally safe when applied superficially to the base of eyelashes , ocular side effects can still occur with risk of instillation onto the eye surface .\nherein , we report an unusual and previously unreported case of upper eyelid ptosis secondary to levator muscle atrophy as a result of the chronic unilateral use of topical bimatoprost .\nclinicians and patients should be aware of this , as it may compromise visual field and be potentially disfiguring , especially when used monocularly .\npatients using latisse should similarly be warned , since the cosmetic and ophthalmic preparations are identical .\nalthough this side effect may not be completely reversible with discontinuation of medication , this case shows that it may be successfully corrected with surgical intervention", "answer": "topical bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma . \n side effects include ocular hyperaemia , ocular pruritus , and periocular and iris pigmentary changes . \n perioribital lipodystrophy is another well - documented outcome associated with chronic use of topical bimatoprost , which results in periorbital hallowing , upper eyelid sulcus deepening , eyelid retraction and enophthalmos . \n we report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use . \n our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye . \n clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle , suggesting that effects of topical bimatoprost may not be limited to periorbital fat . \n she was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully . \n ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost , as it may be potentially disfiguring , especially with monocular use . \n however , its exact mechanism of action needs to be clarified further .", "id": 401} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity\n\nPaper sections:\n1. Introduction\nHypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes which encode sarcomeric proteins [1\u20134]. The most frequently affected genes are MYH7 [5], MYBPC3 [6], and TNNT2 [7], coding for the heavy chain of myosin, the myosin-binding protein-C, and troponin T, respectively. More than 200 mutations have been described in these genes. Furthermore, mutations in a number of other genes, for example, mitochondrial genes [8] have been associated with HCM, albeit at a much lower frequency. Among the rare causes of HCM [9] are mutations in MYL3 which encodes the myosin essential light chain (ELC) of the sarcomere [4, 10\u201319]. The ELC is located at the lever arm of the myosin head and stabilises this region (Figure 1) through interaction with the IQ1 motif [20, 21] at aminoacid residues 781\u2013810 [22] in beta myosin. The N-terminus of ELC interacts with actin [23]. Although the precise functional role of ELC has not been defined [24], the protein belongs to the EF-hand family of Ca2+-binding proteins [25] and appears to be involved in force development and fine tuning of muscle contraction [26, 27]. The phosphorylation of a C-terminal serine residue has recently been shown to be of major significance for cardiac contraction [28] in zebra fish.
To date, nine HCM-causing mutations have been described in MYL3. Three missense mutations, p.E56G, p.A57G, and p.R81H, have been found in exon 3 and six, p.G128C p.E143K, p.M149V, p.E152K, p.R154H, and p.H155D in exon 4 [4, 10\u201319] (Figure 2).
The described phenotypes of ELC mutations vary considerably [24], from HCM with an autosomal dominant inheritance and sudden death events, as in p.A57G [13, 17] and p.M149V [10], to a recessive phenotype where only homozygosity was associated with sudden cardiac death [14]. The penetrance is high in middle-aged mutation carriers [24].
Here, we describe a family with a novel MYL3 mutation characterised by low expressivity and late onset of disease.
\n\n2. Materials and Methods\nThe proband and family members were subjected to a full clinical evaluation including family history, physical examination, echocardiography, stress test, and 12-lead electrocardiograph (ECG). Disease status for the proband and family members was determined using conventional diagnostic criteria [29, 30]. All family members gave informed consent for genetic testing, while for testing of children, consent was obtained from the parents.
Genomic DNA was extracted from blood samples using a QIAamp DNA purification kit (Qiagen, Germany). DNA from the proband was screened for mutations in the coding regions of MYH7, MYBPC3, TNNT2, TPM1, TNNI3, MYL3, MYL2, ACTC, TCAP, and CSRP3, and exons 3, 7, 14, 18, and 49 of TTN, as detailed in a previous study [5]. The primers and conditions used for screening MYL3 have previously been described [9]. Three-hundred ethnically matched Caucasian controls were used to establish frequencies of genetic variants.
Polyphen2 (http://genetics.bwh.harvard.edu/pph2/) was used to predict the effect of the identified ELC variant (p.V79I) [31].
The modelling of ELC and regulatory domain of MYH7 was performed using PDB Protein Workshop (http://www.rcsb.org/) and the PdB file 1WDC [32]. Homology studies and gene-structure studies were performed using BioEdit vers 7.0.9 [33] and Ensembl (http://www.ensembl.org/).
\n\n3.1. Family History\nThe proband, a 38-year-old obese (BMI = 44) man, was referred for clinical assessment following the identification of a cardiac murmur during routine health check. He was asymptomatic and had never experienced cardiac symptoms, systemic hypertension, or syncope. Echocardiography demonstrated asymmetrical septal ventricular hypertrophy becoming more concentric towards the apex (max WT 21\u2009mm), a resting left ventricular outflow gradient (36\u2009mm\u2009Hg) and left atrial dilation (54\u2009mm) (Table 1). Genotyping of 11 sarcomere genes showed him to be heterozygous carrier of a novel missense mutation (c.235G > A), p.V79I, in MYL3, which encodes the ELC of the ventricle. PolyPhen2 prediction of the p.V79I mutation indicated this variant to be \"possibly damaging\". The family was offered screening for the mutation and clinical evaluation (see Figure 3 for the pedigree and Table 1 for clinical data on family members).
Examination of the family members resulted in the identification of nine additional heterozygous carriers of the p.V79I mutation, none of whom fulfilled the diagnostic criteria for HCM. Three mutation carriers, see Figure 3 and Table 1, exhibited a borderline phenotype, either based on the presence of an angulated septum in combination with T-wave inversion in AVL on the ECG or diastolic dysfunction in association with left axis deviation (LAD) or LAD and QRS deviation on the ECG. One mutation carrier, a 29-year-old male, exhibited intraventricular conduction defect (IVCD) as an isolated abnormality. The three borderline cases were 58, 55, and 36 years of age, whereas the remaining asymptomatic mutation carriers were 3, 8, 11, 17, 23, and 29 years of age. None of the family members shown in the pedigree had experienced cardiac events or sudden death, but the grandfather of the proband (I-1) was said to have died suddenly and unexpected at the age of 55 years; while a sister (II-6) to the mother had died suddenly and unexpected at the age of 19 years. No information was available as to the cause of these deaths that occurred 4-5 decades ago, and no DNA was available for analysis. As none of the mutation carriers, including the patient with HCM, had any symptoms, severe disease expression, or risk markers, the mutation was considered benign. However, all mutation carriers were offered a follow-up evaluation.
The mutation was not found in 300 controls and had not been registered as a variant in the NCBI SNP databases (dbSNP). Furthermore, there were no clinically affected or borderline cases among the nonmutation carriers.
The p.V79I is a novel variant, which is located in exon 3 in the region where two other HCM-associated missense mutations have previously been identified (Figure 2). Multiple species alignment of MYL3 in seven species indicate that valine is strongly conserved at this position (Figure 4). We examined the location of the p.V79I mutation in the three-dimensional structure of ELC by interpolating the human structure on the structure established for the scallop myosin regulatory domain (Figure 5). The mutation is located on the linker connecting the N- and C-terminal lobes and it is located just two aminoacid residues from the N-C connecting-loop interacting with the first IQ1 motif on myosin (aa 780\u2013810) (Figure 5) [34]. It is possible that the more nonpolar, longer side chain of the isoleucine residue may disrupt interaction of ELC with the positively charged lysine and arginine residues of myosin heavy chain that interface with this ELC region [35].
\n\n4. Discussion\nWe have described a patient with mild HCM associated with a novel, dominantly inherited, MYL3 mutation p.V79I. The mutation segregates with disease and is absent in 600 control alleles in a family in which no other mutation was identified in known HCM-associated genes. The phenotypic presentation of the p.V79I mutation is that of classical HCM with asymmetric septal hypertrophy, just as previously described for the p.A57G mutation in two unrelated Korean families [13, 17] but distinct from the rare midcavitary obstruction previously described in patients with p.E143K [14], p.M149V, and p.R154H mutations [15]. Expression was reduced and/or the disease exhibited late occurrence, as nine mutation carriers were asymptomatic and did not fulfil diagnostic criteria for HCM, and no mutation carriers below 35 years of age were affected or even borderline affected. However, four of the mutation carriers, all >35 years of age, exhibited either a borderline phenotype or ICVD. Strictly defined, the mutation has a penetrance of 10%, but as many of the carriers are below 25 years. If we define the phenotype as borderline HCM with a late onset, we can say that all mutation carriers above the age of 35 exhibit this phenotype. However, a more precise definition of the penetrance of disease will depend on followup studies. Unfortunately, it was not possible to obtain more information about the sudden deaths occurring in the two potential mutation carriers, I-1 and II-6, 4-5 decades ago. However, their existence supports that the mutation carriers are offered clinical follow-up.
The part of beta myosin containing the IQ1 motif that interacts with the N-C-loop of ELC harbours a number of HCM-associated mutations, that are, p.S782D [36], p.S782N [35], p.R787H [4], p.L796F [1], and p.A797T [37], supporting the concept that interference with the interaction between ELC and beta myosin results in HCM. Another part of the beta myosin molecule that comes into close contact with ELC is the arginine residue at position 723 [35], and mutations here also result in HCM, for example, p.R723G [38] and p.R723C [39], which further supports the concept that interference with the interaction between ELC and myosin is a pathogenetic substrate of HCM.
Homology modelling suggests that the p.V79I mutation may interfere with the interaction between ELC and myosin heavy chain, a mechanism which is believed to be the cause of disease for a number of reported mutations. Based on this evidence we find it likely that the p.V79I mutation is disease causing. However, it can not be ruled out that the mutation may only be associated with hypertrophy when other triggering conditions are present. In this case, the proband is very obese; obesity has recently been associated with a cardiac hypertrophic response in mice fed a high-fat diet through inactivation of the Foxo3a transcription factor via the Akt pathway [40]. As the cardiac hypertrophic response in the same mouse model is associated with increased caspase activity [40] and caspase has ELC [41] as its primary substrate in the failing heart, obesity may aggravate the development of a hypertrophic phenotype in conditions with reduced ELC functionality. A less specific aggravation of hypertrophy through the leptin-induced cardiac hypertrophic response seen in neonatal rat cardiomyocytes phenotype could also explain that the proband is the only mutation carrier with clinical HCM [42].
The finding of a clinically silent mutation with low expressivity and late onset raises the question of whether it should entail a detailed followup of mutation carriers. However, as most mutations in MYL3 have been associated with sudden death [24], it would seem prudent to conduct a clinical followup of mutation carriers. The potential relation between a MYL3-based genetic predisposition, the hypertrophic phenotype and obesity in the proband should also strengthen the recommendation to the proband to lose weight.
", "answer": "Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, in MYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion, MYL3 mutations can present with low expressivity and late onset.", "id": 402} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nobesity is a leading risk factor for many adverse health outcomes including type 2 diabetes , hypertension , dyslipidemia , coronary heart disease , and certain types of cancer .\nthe prevalence of adult obesity in the us had doubled from 19761980 to 1999 - 2000 . in 2009\nus ranked the highest in adult obesity prevalence among all countries in the organization for economic cooperation and development .\nthe estimated annual medical cost of obesity in the us totaled 147 billion us dollars in 2008 .\nmore recent data indicated a slowing down of the trend in adult obesity and even some leveling off in childhood obesity .\nsmall but significant declines in the prevalence of obesity among low - income preschoolers aged 25 years were reported in 19 of 43 us states examined in the pediatric nutrition surveillance system from 2008 to 2011 .\nno significant change in the prevalence of adult obesity was found between 20032008 and 2009 - 2010 in the national health and nutrition examination survey ( nhanes ) .\nthe prevalence of morbid ( i.e. , grades 2 and 3 ) obesity was still increasing from 2005 to 2010 , but its growth rate had slowed down as indicated in the behavioral risk factor surveillance system ( brfss ) . given the large disease burden of obesity and its high prevalence , it is crucial to continuously monitor the prevalence of obesity in the us .\nthis study provides national estimates of obesity among us adults aged 20 years and older in 2011 - 2012 and tracks its trends from 1999 to 2012 .\nstudy sample came from nhanes 1999 - 2000 , 2001 - 2002 , 2003 - 2004 , 2005 - 2006 , 2007 - 2008 , 2009 - 2010 , and 2011 - 2012 waves .\nnhanes is a program of studies designed to assess the health and nutritional status of adults and children and represents a multistage probability sample of the us civilian , noninstitutionalized population .\nparticipants ' body weight and stature height were measured by digital scale and stadiometer in the nhanes mobile examination center .\nbody mass index ( bmi ) is defined by weight in kilograms divided by height in meters squared .\nfour prevalence measures were examined : overweight and obesity combined ( bmi 25 ) , obesity ( bmi 30 ) , grades 2 and 3 obesity combined ( bmi 35 ) , and grade 3 obesity ( bmi 40 ) .\nage was adjusted by direct standardization to the year 2000 census population using the age groups 2039 years old , 4059 years old , and 60 years and older .\nnhanes wave - specific sampling weight , sampling stratum , and primary sampling unit were taken into account in estimating prevalence in the population .\nprevalence was estimated for both the overall population and subpopulations stratified by gender and race / ethnicity ( i.e. , non - hispanic white , non - hispanic african american , and hispanic ) .\npiecewise logistic regressions were used to test the differential trends in adult obesity before and after 2010 .\nthe model has the following setup : \n ( 1)logit(yi)=0+1xi+2(xi2010)di+i , di=1{xi2010}. in ( 1 ) , yi is an indicator variable for overweight and obesity combined ( bmi 25 ) , obesity ( bmi 30 ) , grades 2 and 3 obesity combined ( bmi 35 ) , or grade 3 obesity ( bmi 40 ) ; xi a continuous variable taking the values of 2000 , 2002 , 2004 , 2006 , 2008 , 2010 , and 2012 for the nhanes waves 1999 - 2000 , 2001 - 2002 , 2003 - 2004 , 2005 - 2006 , 2007 - 2008 , 2009 - 2010 , and 2011 - 2012 , respectively ; di an indicator variable for xi 2010 ; and i the error term . if the estimated coefficient 2 is significantly different from zero ( equivalent to the estimated odds ratio e to be significantly different from one ) ,\npiecewise logistic regressions were performed on the overall sample and on each gender and race / ethnicity group , controlling for age group ( i.e. , 2039 years old , 4059 years old , and 60 years and older ) and accounting for survey design .\nin total , 5,560 adults aged 20 years and older participated in the nhanes 2011 - 2012 wave . among them , 57 pregnant women and 322 individuals with missing values in body weight / height measures were excluded from the analyses . \nnhanes oversamples minorities : 1,364 non - hispanic african americans and 1,037 hispanic were included besides non - hispanic white . \n\ntable 2 reports the estimated bmi and prevalence measures among us adults aged 20 years and older in 2011 - 2012 .\nthe age - adjusted mean bmi was 28.5 ( 95% ci : 28.029.0 ) among men and 28.8 ( 28.329.3 ) among women .\nnon - hispanic african american women had the highest mean bmi of 32.3 ( 31.633.0 ) among all gender and race / ethnicity subgroups .\nthe age - adjusted prevalence of overweight and obesity combined ( bmi 25 ) was 71.1% ( 68.0%74.2% ) among men and 65.5% ( 61.8%69.3% ) among women , and the age - adjusted prevalence of obesity ( bmi 30 ) was 33.3% ( 30.5%36.2% ) among men and 35.8% ( 32.3%39.4% ) among women . among men , 11.8% ( 9.7%13.9% ) and 4.3% ( 2.2%6.3% )\nwere classified in grades 2 and 3 obesity combined ( bmi 35 ) and grade 3 obesity ( bmi 40 ) , respectively , whereas among women , 16.7% ( 14.5%8.9% ) and 8.0% ( 6.6%9.5% ) were classified in grades 2 and 3 obesity combined and grade 3 obesity , respectively .\nwomen had higher prevalence of obesity , grades 2 and 3 obesity combined , and grade 3 obesity than men ( although the differences were not always statistically significant ) among all race / ethnicity groups .\nnon - hispanic african american women had the highest prevalence of overweight and obesity combined ( 81.5% ) , obesity ( 56.4% ) , grades 2 and 3 obesity combined ( 28.7% ) , and grade 3 obesity ( 15.8% ) among all gender and race / ethnicity groups , which were 29% , 73% , 92% , and 122% higher than among non - hispanic white women , respectively . \n\nfigure 1 shows the percentage change in prevalence measures among us adults of 20 years and older from 1999 - 2000 to 2011 - 2012 with 1999 - 2000 as the baseline .\nthe age - adjusted prevalence of overweight and obesity combined ( bmi 25 ) , obesity ( bmi 30 ) , grades 2 and 3 obesity combined ( bmi 35 ) , and grade 3 obesity ( bmi 40 ) in 2009 - 2010 were 7.2% , 17.8% , 17.6% , and 33.0% higher than in 1999 - 2000 . compared to 2009 - 2010 ,\nthe prevalence measures slightly decreased in 2011 - 2012 , but the reductions were not statistically significant at p < 0.05 . \n\nfigure 2 shows the gender- and race / ethnicity - specific trend in the age - adjusted prevalence of overweight and obesity combined ( bmi 25 ) , obesity ( bmi 30 ) , grades 2 and 3 obesity combined ( bmi 35 ) , and grade 3 obesity ( bmi 40 ) among us adults aged 20 years and older from 1999 - 2000 to 2011 - 2012 .\ncompared to 2009 - 2010 , most gender- and race / ethnicity - specific prevalence measures remained unchanged or slightly decreased in 2011 - 2012 , except for the prevalence of overweight and obesity combined among non - hispanic white women , the prevalence of obesity among hispanic men , and all 4 prevalence measures among hispanic women which increased by 1.3 to 3.3 percentage points .\nnone of the changes in gender- and race / ethnicity - specific prevalence measures ( 24 of them in total ) between 2009 - 2010 and 2011 - 2012 were statistically significant at p < 0.05 . \n\ntable 3 reports the statistical tests for trends in obesity over the 14 years of survey cycles from 1999 to 2012 using piecewise logistic regressions .\nthe coefficients are expressed as annualized odds ratios ( ors ) , denoting the estimated increase per year in the odds of a prevalence measure .\na majority of the gender- and race / ethnicity - specific prevalence measures seemed to slightly increase over time ( as indicated by the estimated e > 1 ) .\nfor example , the estimated or for the prevalence of obesity ( bmi 30 ) among hispanic women is 1.03 ( 1.011.04 ) , approximately equivalent to a yearly increase in obesity prevalence of 0.6 percentage points .\nnearly all gender- and race / ethnicity - specific prevalence measures appeared to deviate downwards from the increasing trend ( as indicated by the estimated e < 1 ) during 20102012 , but those changes in trends were not statistically significant at p < 0.05 .\nthe rate of increase appeared to slow down since the 2000s and most recent data on childhood obesity even indicated some leveling off . using a nationally representative sample ,\nthis study estimates the obesity prevalence among us adults aged 20 years and older in 2011 - 2012 and tracks its trends from 1999 to 2012 . the main advantage of nhanes relative to other national health surveillance systems such as the brfss and the national health interview survey ( nhis ) is the objectively measured body weight and height , which eliminates self - report bias .\nhowever , the relatively small sample size of nhanes ( about 5,000 in every two - year survey cycle , compared to about 0.4 million a year in brfss ) limits the precision for population estimates . unlike brfss or nhis , nhanes\nmoreover , nhanes is a probability sample of the us civilian , noninstitutionalized population , excluding inmates of institutions ( e.g. , people in penal / mental facilities or homes for the aged , or on active duty in the armed forces ) .\nthe prevalence measures are based on bmi , a function of weight and height , rather than on body fatness .\nalthough bmi has been found to be closely associated with percentage body fat measured by dual x - ray absorptiometry in the nhanes , these two measures are fundamentally different and their levels of agreement could be a function of gender , age , and race / ethnicity .\nfor instance , percentage body fat was found to be more correlated with bmi in women than men .\nthe relation between percentage body fat and bmi in hispanic american women differed from that of african american and european american women . a thorough investigation on the differential relationship between bmi and body fatness across population groups and the long - term trend of obesity prevalence measured by percentage body fat is beyond the scope of this study but warranted in future research .\nthe growth rate of the obesity epidemic among us adults appears to have slowed down in 2000s , but it is still too early to conclude that it has already reached the plateau and begun to level off . both figures 1 and 2 showed some decline in the obesity prevalence measures in 2011 - 2012 compared to in 2009 - 2010 , but none of the changes were statistically significant .\nthis has also been indicated in the results of piecewise logistic regressions where the null hypotheses on the similarity in trends for prevalence measures before and after 2010 were not rejected . in conclusion ,\nconcurrent evidence on the leveling off of the obesity epidemic in the us is thin and the trend is unclear and inconclusive at this time . given the high prevalence of obesity and its profound socioeconomic consequences , close monitoring of the trend is warranted .", "answer": "aim . to provide national estimates of obesity among us \n adults aged 20 years and older in 2011 - 2012 and track its trends from 1999 to 2012 . \n methods . measured weight / height from national health and nutrition examination survey 19992012 waves was used to calculate body mass index ( bmi ) and prevalence measures . \n piecewise logistic regressions were conducted to test the differential trends before and after 2010 . \n results . in 2011 - 2012 , the age - adjusted prevalence of overweight and obesity combined ( bmi 25 ) was 71.1% ( 95% ci : 68.0%74.2% ) among men and 65.5% ( 61.8%69.3% ) among women , and the prevalence of obesity ( bmi 30 ) was 33.3% ( 30.5%36.2% ) among men and 35.8% ( 32.3%39.4% ) among women . from 19902000 to 2009 - 2010 , the prevalence of overweight and obesity combined , obesity , grades 2 and 3 obesity combined ( bmi 35 ) , and grade 3 obesity ( bmi 40 ) increased by 7.2% , 17.8% , 17.6% , and 33.0% , respectively . compared to 2009 - 2010 , most gender- and race / ethnicity - specific prevalence measures remained unchanged or slightly decreased in 2011 - 2012 . \n no significant difference in trends among prevalence measures was found before and after 2010 . \n conclusions \n . concurrent evidence on the leveling off of obesity in the us is thin . \n given its high prevalence and profound socioeconomic consequences , close monitoring of the trend is warranted .", "id": 403} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntiam1 is involved in a number of cellular processes including migration and the regulation of cell - cell adhesions and survival .\nalthoughtiam1 has been implicated in cellular proliferation , its role during the cell cycle is unknown . in mdck\nii cells expressing either gfp - tagged tiam1 or ha - tagged tiam1 , we were intrigued to observe a signal not only at cell - cell adhesions ( as previously described ) but also at the two microtubule ( mt ) asters surrounding the centrosomes .\nthis localization was apparent both before nuclear envelope breakdown ( nebd ) in prophase cells ( figure 1a and figure s1a , available online ) and after nebd in prometaphase cells ( figure 1b and figure s1b ) and was dependent on mts because it was lost after nocodazole treatment ( data not shown ) .\nhowever , in metaphase cells , tiam1 localization to centrosomal regions was no longer detected ( right - hand cell , figure 1b ) . to investigate the potential function of tiam1 at centrosomes , we generated mdck ii cells expressing doxycycline - inducible short hairpin interfering rnas ( shrnas ) to tiam1 ( two independent targets : rnai # 1 and rnai # 2 ) or control scrambled shrna ( scr ) . upon doxycycline addition , endogenous\ntiam1 protein was depleted from cells containing either tiam1 shrna target ( figure 1c ) . in subcellular fractions enriched for centrosomes ,\nendogenous tiam1 cosedimented with the centrosomal marker -tubulin and was depleted from these fractions after tiam1 shrna expression ( figures s1c and s1d ) .\nmoreover , immunofluorescence analysis confirmed that endogenous tiam1 localized to centrosomal regions in early mitosis ( figures 1d and s1e ) ; this signal was depleted after tiam1 shrna expression ( figure 1d ) . because tiam1 is a rac - specific activator\ngfp - tagged rac was detected at cell - cell adhesions as shown previously ; however , it also colocalized with the two mt asters in prophase ( figure 1e ) and prometaphase cells ( figure s1f ) .\nendogenous rac showed a similar localization ( figure 1f and figure s1 g ) .\nhence , tiam1 and rac localize to centrosomal regions in early mitosis . during prophase ,\nduplicated centrosomes begin to separate around the nuclear envelope before nebd ( prophase pathway ) , in preparation to form a bipolar spindle in prometaphase .\nhence , we measured centrosome separation in control and tiam1-depleted prophase cells . strikingly , the intercentrosomal distance increased by over 40% in tiam1-depleted cells ( figure 2a ) .\nthis defect was efficiently rescued by expressing rnai - resistant wild - type tiam1 ( figure 2a ) but not the gef mutant tiam1 ( q1191a , k1195a ) , which is unable to activate rac ( figure 2a ) .\ntreatment with a specific rac inhibitor ( nsc-23766 ) also increased centrosome separation in prophase cells ( figure s2a ) .\nafter tiam1 depletion , a similar increase in centrosome separation was seen in mouse p1 cells ( figures s2b and s2c ) . thus , tiam1 functions via rac to oppose centrosome separation in prophase .\nrelatively little is known about centrosome separation during prophase , with conflicting evidence for the involvement of eg5 [ 13 , 14 ] .\ntreatment with the eg5-specific inhibitor monastrol led to a significant decrease in the intercentrosomal distance of prophase mdck ii cells ( figure 2b ) ; similar results were obtained with a second eg5-specific inhibitor s - trityl - l - cysteine ( stlc , data not shown ) .\ntiam1 also localizes to the cortex in prophase cells ( figure 1a and figure s1a ) , and cortical movements driven by myosin - ii activity ( regulated by rho kinase [ rock ] ) are required after nebd for centrosome separation via astral mt connections . to gain mechanistic insight into the regulation of centrosome separation in prophase\n, we treated cells with inhibitory concentrations of blebbistatin ( myosin - ii inhibitor ) or y-27632 ( rock inhibitor ) ( figures s2d and s2e ) .\nhowever , neither treatment affected centrosome separation in control prophase cells ( figure 2b ) or the increased intercentrosomal distance in tiam1-depleted prophase cells ( figure 2c ) .\nin contrast , low concentrations of taxol , a mt - stabilizing agent , although not effecting centrosome separation in control cells , prevented the increased centrosomal separation of tiam1-depleted prophase cells ( figure 2c ) .\nthese data suggest that in prophase , centrosome separation is driven by eg5 but is unlikely to involve cortical movements .\nfurther , the effects of tiam1 depletion on centrosome separation , although probably independent of the cortex , may be mediated through microtubule stabilization , although how is currently unclear . a role for tiam1 in stabilizing mts during front - rear polarization in cell migration\nwe detected no change in the localization of eg5 in tiam1-depleted cells ( data not shown ) , suggesting that this is independent of tiam1 . using time - lapse fluorescence microscopy of cells expressing -tubulin - gfp\nafter tiam1 depletion , there was no significant difference in the period between the onset of centrosome separation and nebd compared with controls ( figure 2d ) .\nhowever , the centrosome separation rate in prophase was significantly increased in tiam1-depleted cells compared to controls ( figures 2d and 2e ) .\nfurther , tiam1-depleted cells maintained their increased centrosome separation after nebd ( figure s2f ) .\nconsistent with this , the intercentrosomal distance in prometaphase from fixed samples was also significantly increased after tiam1 depletion ( figure s2 g ) or rac inhibition ( figure s2h ) . however , the rate of centrosome separation during prometaphase was markedly reduced compared to prophase and was unaffected by tiam1 depletion ( figure 2e ) . to investigate further the role of tiam1 in centrosome separation in prometaphase , we arrested cells in a monopolar prometaphase state with monastrol , then released them to allow mitosis to proceed .\nwe found that centrosomes in tiam1-depleted cells separate significantly further 10 min after washout compared to controls ; however , at 20 min the increase was not significant ( figure s2i ) .\nthus , tiam1-rac affects centrosome separation apparently independently of the nuclear envelope and seemingly more potently when centrosomes are in close proximity .\nthis property may account for the greater influence that inhibition of this pathway exerts during prophase compared to prometaphase . to examine whether tiam1 antagonizes eg5 during bipolar spindle formation , we treated control and tiam1-depleted cells for 18 hr with stlc or monastrol at concentrations that reduce but do not abolish eg5 activity . in controls ,\neg5 suppression resulted in mainly monopolar mitotic spindles ( figure 3a ) : 60% in stlc - treated cells ( figure 3b ) and 70% in monastrol - treated cells ( figure s3a ) .\nhowever , after tiam1 depletion , mitotic spindles were mainly bipolar ( figure 3a ) , with significantly fewer monopolar spindles : 15% in stlc - treated ( figure 3b ) and 30% in monastrol - treated cells ( figure s3a ) .\nwe next confirmed that the bipolar spindles formed in tiam1-depleted cells , under conditions of eg5 suppression , were functional and able to segregate chromosomes later in mitosis .\nin control cells , the proportion of mitotic cells in anaphase or telophase significantly reduced from over 32% to 20% after stlc ( figure 3c ) and 12% after monastrol treatment ( figure s3b ) .\nconversely , in tiam1-depleted cells , eg5 suppression had little effect on the proportion of mitotic cells in anaphase or telophase : 32% after stlc ( figure 3c ) and over 25% after monastrol treatment ( figure s3b ) .\nconsistent with this , in controls the mitotic index increased by over 4.5-fold after eg5 suppression ( figure 3d and figure s3c ) as a result of the monopolar spindles activating the spindle assembly checkpoint ( sac ) , thereby delaying mitosis .\nhowever , tiam1 depletion prevented the accumulation of mitotic cells after eg5 suppression ( figure 3d and figure s3c ) . to determine whether eg5 function is antagonized by rac signaling in vivo , we utilized conditional rac1 knockout mice , focusing on the intestinal epithelium .\nepithelial cells within intestinal crypts are highly proliferative and arrest rapidly after administration of various drugs ; this arrest is visualized via an accumulation of mitotic figures within the intestinal crypt .\nwe first conditionally deleted rac1 within the intestinal epithelium ( as described in the supplemental experimental procedures ) .\nthree days after cre induction , the intestinal epithelium from ahcre rac1 mice showed loss of rac1 ( figures s3d and s3e ) .\ndeletion of rac1 at this stage did not affect proliferation ( data not shown ) or cellularity ( figure s3f ) .\nwe next treated mice with 25 mg / kg stlc and investigated mitotic arrest after 3 hr . in wild - type mice , stlc treatment induced a significant mitotic arrest ( figures 3e and 3f ; rac1 control versus rac1 stlc - treated ) . remarkably , rac1 deletion completely rescued the induction of mitotic arrest ( figures 3e and 3f ; rac1 stlc - treated versus rac1 stlc - treated ) .\nmoreover , in wild - type mice the proportion of mitotic cells in anaphase was significantly reduced after stlc treatment , indicating an arrest prior to this stage ( figure 3 g ) .\ntaken together , these data indicate that tiam1-rac signaling antagonizes eg5 function , both in vitro and in vivo ; in their absence mitotic cells can assemble bipolar spindles and complete mitosis under conditions of reduced eg5 activity .\nwe tested whether tiam1 depletion induced further mitotic defects by using time - lapse fluorescence microscopy of cells expressing histone-2b - gfp . in controls ,\nchromosomes efficiently congressed to the metaphase plate after nebd and rapidly entered anaphase ( figure 4a ) . in over 60% of tiam1-depleted cells , however , chromosomes spent over 15 min aligning on the metaphase plate ( compared to less than 5% of controls ) , before eventually aligning and entering anaphase ( figure 4a ) .\nthe duration of early mitotic stages , calculated from numerous movies , indicated that tiam1 depletion specifically increased prometaphase duration ( figure 4b ) .\nanalysis of fixed mitotic cells revealed that after tiam1 depletion , congression errors were over 2.5-fold higher than controls ( figure 4c ; see figure s4a for example images ) .\nsimilar results were obtained after tiam1 depletion in p1 cells ( data not shown ) .\nimportantly , this chromosome congression defect was efficiently rescued by expressing rnai - resistant wild - type tiam1 , but not gef mutant tiam1 ( figure 4c ) .\nmoreover , cells treated with rac inhibitor also displayed significantly increased congression errors compared to controls ( figure 4d ; see figure s4b for example images ) , consistent with a role for rac downstream of tiam1 .\nwe confirmed that these congression errors observed in tiam1-depleted cells were due to an increased prometaphase duration ( figure s4c ) .\nhence , cells with compromised tiam1-rac signaling fail to efficiently align chromosomes to the metaphase plate , resulting in a prolonged prometaphase .\nthis is probably due to maintained activation of the sac , which delays mitosis until all chromosome kinetochores are captured .\nsubsequently , we determined whether the increased centrosome separation of tiam1-depleted cells leads to the congression errors . using time - lapse fluorescence microscopy of individual mitotic cells expressing -tubulin - gfp\n, we confirmed that in the presence of stlc , the majority of tiam1-depleted mitotic cells formed bipolar spindles ( figure s4d ) ; furthermore , the intercentrosomal distance in prometaphase was now similar to that found in untreated controls ( figure 4e ) .\nsignificantly , correcting the balance of forces during bipolar spindle formation completely rescued the chromosome congression errors resulting from tiam1 depletion ( figures 4f and 4 g ) and restored normal mitotic progression ( figures s4e and s4f ) .\ntogether , these data indicate that the defects in chromosome congression induced by tiam1 depletion are due to the increased centrosome separation . in conclusion\n, we have shown that tiam1 , acting through rac , is a critical mediator of forces during bipolar spindle assembly .\ntiam1-rac signaling counteracts eg5 during bipolar spindle formation in vitro and in vivo .\nto our knowledge , this is the first signaling module that retards centrosome separation during prophase in mammalian cells and the first demonstration of an increased rate of centrosome separation in prophase leading to chromosome congression defects .\nimportantly , we show that correcting the balance of forces , by attenuating eg5 activity in tiam1-depleted cells , completely rescues the defects in chromosome congression , allowing cells to satisfy the sac and progress through mitosis normally ( for a model see figure 4h ) .\nthere are numerous other pathways that promote [ 1 , 3 , 20 ] and oppose [ 13 , 21 ] centrosome separation during bipolar spindle formation .\nthis considerable overlap is not surprising given the importance of the bipolar mitotic spindle to the survival of eukaryotic cells , providing a number of fail - safes that decrease the risk of chromosome segregation errors during cell division .", "answer": "summarycentrosome separation , critical for bipolar spindle formation and subsequent chromosome segregation during mitosis , occurs via distinct prophase and prometaphase pathways [ 13 ] . \n kinesin-5 ( eg5 ) , a microtubule ( mt ) motor , pushes centrosomes apart during bipolar spindle assembly [ 4 ] ; its suppression results in monopolar spindles and mitotic arrest [ 5 , 6 ] . \n forces that antagonize eg5 in prophase are unknown . here \n we identify a new force generating mechanism mediated by the guanine nucleotide exchange factor ( gef ) tiam1 , dependent on its ability to activate the gtpase rac . \n we reveal that tiam1 and rac localize to centrosomes during prophase and prometaphase , and tiam1 , acting through rac , ordinarily retards centrosome separation . \n importantly , both tiam1-depleted cells in culture and rac1-deficient epithelial cells in vivo escape the mitotic arrest induced by eg5 suppression . \n moreover , tiam1-depleted cells transit more slowly through prometaphase and display increased chromosome congression errors . \n significantly , eg5 suppression in tiam1-depleted cells rectifies not only their increased centrosome separation but also their chromosome congression errors and mitotic delay . \n these findings identify tiam1-rac signaling as the first antagonist of centrosome separation during prophase , demonstrate its requirement in balancing eg5-induced forces during bipolar spindle assembly in vitro and in vivo , and show that proper centrosome separation in prophase facilitates subsequent chromosome congression .", "id": 404} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthree types of calibrated microspheres have recently been approved in japan as embolic agents for hypervascular tumors and arteriovenous malformations . to date , two types of embolic microspheres capable of being loaded with drug have been introduced : dc bead ( biocompatibles , farnham , uk ) and hepasphere ( biosphere medical , roissy cdg cedex , france ) . in a phase\nii randomized controlled study of transarterial chemoembolization ( tace ) using a drug - eluting bead ( deb - tace ) for hepatocellular carcinoma ( hcc ) , the precision - v study , the response rate after 6 months was 52% in the deb - tace group and 44% in the tace group using a lipiodol ( laboratoire guerbet , aulnay - sous - bois , france)/anticancer drug mixture solution ( lip - tace ) , showing no significant difference or superiority of deb - tace .\nhowever , complication by postembolization syndrome , such as abdominal pain , fever , nausea , vomiting and liver enzyme elevation , developed in 2080% after lip - tace [ 3 , 4 ] , whereas symptoms developed in only 1837% after deb - tace [ 5 , 6 ] , showing that the complications were milder than those after lip - tace . on the other hand , deb - tace induced liver abscesses at a relatively high frequency , which could be fatal [ 5 , 7 , 8 , 9 ] .\nadverse events after deb - tace have been reported occasionally [ 5 , 7 , 8 , 9 , 10 , 11 ] , but as it has just been introduced in japan , many points regarding adverse events are unclear with respect to the developmental mechanism and risk factors .\nwe encountered a hcc patient who underwent deb - tace and experienced delayed intratumoral hemorrhage .\nan 81-year - old male regularly visited his physician for treatment of hepatitis c virus - related cirrhosis . on routine abdominal ultrasonography ( us ) ,\non esophagogastroduodenoscopy , a type 0-iia early gastric carcinoma with a diameter of 25 mm was detected in the lesser curvature of the middle body .\nthe patient was referred to our hospital for further examination and treatment . during the first examination ,\nthe liver function was classified as child - pugh class a , and the tumor markers were normal ( afp level : 3.4 ng / ml , afp - l3 fraction level < 0.5% ) , but the pivka ii had a level of 118 mau / ml , showing a mild elevation .\nit was capsulated and enhanced in the arterial phase on dynamic computed tomography ( ct ) ( fig .\n1 ) , and showed a mosaic pattern accompanied by a marginal hypoechoic zone on gray - scale us .\nthe mass was enhanced in the vascular phase ( 040 s ) on contrast - enhanced us ( ceus ) using sonazoid ( daiichi sankyo , tokyo , japan ) , and showed a hypoechoic area in the postvascular phase ( 10 min after an intravenous injection of sonazoid ) .\nbased on the tumor marker and imaging findings , the patient was diagnosed with hcc .\ndeb - tace was performed because the patient declined to undergo surgical resection of hcc .\naccess for tace was performed under sterile conditions and under local anesthesia , via the right femoral artery using a 3-fr sheath ( medikit , tokyo , japan ) and in a retrograde fashion .\nwhen a microcatheter was advanced to the anterior segmental artery of the right hepatic artery and contrast imaging was applied , an intensely stained tumor was observed , with a5 as the feeding artery . a solution impregnated with 100300 m dc bead and 50 mg epirubicin hydrochloride , with a dc bead volume of 0.35 ml , was administered via the feeding artery to perform deb - tace .\ndisappearance of the intensely stained tumor image was confirmed by right hepatic arterial angiography , and the treatment was completed .\nthe course after deb - tace was favorable , and no adverse events above grade 3 according to the common terminology criteria for adverse events ( ctcae ) version 4.0 were observed .\nendoscopic submucosal dissection ( esd ) of the early gastric carcinoma was performed about 1 month after deb - tace .\nright hypochondriac pain suddenly developed 3 days after esd , but no adverse events were assumed to be caused by esd ( i.e. , free air , noted on dynamic ct ) .\nhowever , the tumor diameter had increased from that before deb - tace , and the tumor showed a high - intensity area on unenhanced ct ( fig .\n2a ) , which was not enhanced in the arterial phase on dynamic ct , suggesting intratumoral hemorrhage .\nthe hemodynamics of the tumor were followed using ceus over the time before and after deb - tace .\non ceus carried out on the day after deb - tace , the whole intratumoral enhancement decreased , and nonenhanced patchy regions , assumed to be necrosis , were noted in the tumor in the vascular phase . on ceus\nperformed 4 weeks after deb - tace , i.e. , immediately before esd , the tumor size was 33 31 mm , and the enhancement area was increased in the vascular phase ( fig .\nhowever , the tumor had enlarged to 41 36 mm on ceus when the right hypochondriac pain developed ( 5 weeks after deb - tace ) , and changes in the echogenicity on gray - scale us and nonenhancement of almost the entire tumor in the vascular phase on ceus were noted ( fig .\nbased on the above findings , the cause of right hypochondriac pain may have been deb - tace - associated intratumoral hemorrhage .\nsince the hemorrhage was limited to inside the tumor , it stopped spontaneously with rest .\nthe advantages of deb - tace are as follows : the infusion dose of the chemotherapeutic agent can be modified by adjusting the chemotherapeutic agent carrier , while altering the depth of embolization with beads , the duration of tumor exposure to chemotherapeutic agent can be fine - tuned through sustained release of the chemotherapeutic agent , and systemic adverse reactions of chemotherapeutic agent can be attenuated by continuous release of high - dose chemotherapeutic agents into the tumors .\ndeb has proven to be extremely potent and safe by allowing large amounts of the chemotherapeutic agent to concentrate within the tumor over time , thereby maximizing the cytotoxic effect , which also makes it attractive as an effective treatment for large lesions .\nfavorable therapeutic effects have been reported occasionally [ 8 , 9 ] and have increased the expectations of hcc treatment with deb - tace ; however , the beads exhibit characteristic physical properties and behavior that are different from those of gelatin particles .\nit is important to fully investigate these characteristics to avoid inadequacy of the therapeutic effect and to prevent the onset of adverse events .\nprevious studies have reported that the incidence of mild adverse events , such as postembolization syndrome , is lower in the deb - tace group compared with the lip - tace group [ 3 , 4 , 5 , 6 ] .\nmeanwhile , liver abscesses were induced at a relatively high frequency ( about 1.67.4% ) [ 5 , 7 , 8 , 9 ] .\nmalagari et al . reported that the 30-day mortality was 1.26% among 237 hcc patients treated with deb - tace with dc bead loaded with doxorubicin , and that the cause was liver abscess in all cases .\nregarding other adverse events , acute pancreatitis and cholecystitis developed with incidences of 15 and 16.3% , respectively .\nprevious studies have shown that rare adverse events included liver failure and infection , bile duct injury , upper gastrointestinal bleeding , pulmonary embolism , splenic infarction , or spinal embolization [ 1 , 7 , 10 , 11 ] .\nunlike lip - tace , many adverse events occurred due to ischemic changes induced by the inflow of beads into organs other than the hcc lesion , which is characteristic of deb - tace .\ntumor hemorrhage has also been reported after deb - tace [ 1 , 7 , 10 , 11 , 13 ] with large tumors , with a diameter of 516 cm , and the tumor locations were subcapsular in all previous reports . to our knowledge , there has been no case of a tumor with a diameter < 5 cm distinct from the subcapsular , as was observed in our patient .\nthere has been no report of a mechanism underlying the deb - tace - specific tumor hemorrhage . in general\n, the mechanism of tumor rupture after tace might be related to increased intratumoral pressure as a result of rapid edematic expansion due to tumor necrosis or vascular injury , secondary to embolization .\nthe risk is particularly high in subcapsular lesions , and we must be careful because the spread of hemorrhage in the abdominal cavity can not only lead to hemorrhagic shock , but also peritoneal metastasis .\nunlike the reported cases of tumor hemorrhage after deb - tace , in the present case , the tumor diameter was not large and the tumor was distinct from the subcapsular region .\nhowever , intratumoral hemorrhage occurred about 1 month after deb - tace . local pooling of the contrast agent within the target tumor could occur during deb - tace , and seki et al . \nreported that it occurred in 25.2% of 135 hcc patients treated with deb - tace ( epirubicin - loaded hepasphere ) .\nwhile the cause of this local pooling remains unclear , it is similar to extravasation or blood sinus , suggesting that it was a local hemorrhage due to intratumor vascular collapse as a consequence of the treatment .\nwhen local pooling of the contrast agent was noted , seki et al . added a small amount of gelatin sponge particles , with a diameter ranging from 1 to 2 mm , to the feeding artery until the pooling disappeared .\nbased on the above findings , the observation of local pooling of the contrast agent within the target tumor during treatment suggests that intratumoral pressure has already increased , which was unlikely in our patient .\ntreatment - induced intratumoral hemorrhage continued immediately after deb - tace because no pooling was noted during treatment or on confirmation angiography following treatment .\nhowever , it is possible that the amount of dc bead was insufficient and embolization was incomplete .\nit was assumed that incomplete embolization subsequently caused intratumoral vascular collapse , i.e. , a phenomenon similar to pooling , and that the hemorrhage expanded to the necrotic intratumoral area by sustained release of the chemotherapeutic agent and embolization , leading to complication of intratumoral hemorrhage despite the low risk of tumor hemorrhage .\nmany points remain unclear , i.e. , the appropriate bead sizes for each case and the level of embolization , but it may be important to apply sufficient embolization because insufficient embolization is likely to lead to tumor hemorrhage .\ndeb - tace is considered to rarely cause adverse events , but fatal complications have been reported [ 5 , 7 , 8 , 9 ] , and reports of adverse events may increase with augmentation of the numbers of deb - tace - treated patients . if reports of tumor hemorrhage after deb - tace increase , the mechanism of intratumoral hemorrhage in cases similar to our patient may be elucidated .\nintratumoral hemorrhage was suspected due to the presence of a high - intensity area in the tumor on unenhanced ct and a rapid increase in the tumor diameter and accompanying enlargement of the unenhanced area on ceus performed before and after deb - tace . based on these findings\nit was difficult to assess the therapeutic effect of deb - tace by ct , based on lipiodol accumulation , unlike that after conventional lip - tace , and evaluation of the intratumoral hemodynamics could be important .\nceus is superior in evaluating intratumoral hemodynamics in real time , and the utility of ceus to evaluate the therapeutic effect after deb - tace was suggested .\nwe encountered a patient who experienced intratumoral hemorrhage about 1 month after deb - tace .\ndeb - tace for hcc is a new treatment method in japan , and reports of adverse events may increase in the future . to obtain the therapeutic effect of deb - tace while preventing the adverse events , it may be important to understand the characteristics of the beads themselves and to apply the appropriate embolization to each individual case .\nit was also suggested that ceus is useful to evaluate the therapeutic effect after deb - tace .", "answer": "transarterial chemoembolization ( tace ) using a drug - eluting bead ( deb - tace ) for hepatocellular carcinoma ( hcc ) is a new treatment method . \n we report on a case of delayed intratumoral hemorrhage after deb - tace . \n an 81-year - old male with hepatitis c virus - related cirrhosis was diagnosed with a hcc of 35 mm in diameter in s5 detected by dynamic computed tomography ( ct ) and contrast - enhanced ultrasonography ( ceus ) . \n deb - tace with dc bead and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection . \n the treatment was completed , and the course after deb - tace was favorable . however , right hypochondriac pain suddenly developed about 1 month after deb - tace . \n unenhanced ct showed an increase of the tumor diameter and intratumoral high - intensity area , which was not enhanced in the arterial phase . \n ceus performed at the time of right hypochondriac pain ( 5 weeks after deb - tace ) showed nonenhancement of almost the entire tumor in the vascular phase . \n the cause of the symptom may have been deb - tace - associated intratumoral hemorrhage . \n tumor hemorrhage has been reported after deb - tace with tumors > 5 cm in diameter , and the tumor locations were subcapsular in all previous reports . there has been no case of a tumor with a diameter < 5 cm distinct from the subcapsular , as was observed in our patient . \n incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks . to obtain the therapeutic effect of deb - tace while preventing the adverse events \n , it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case .", "id": 405} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese include evolution from fiberoptic imaging to generation of images using a charge - coupled device and high definition digital imaging .\nenhanced endoluminal imaging techniques have included chromoendoscopy and modalities that aspire to optical biopsy . among techniques for enhanced optical diagnosis , narrow band imaging ( nbi )\nis a proprietary imaging modality in which the endoscope processor filters standard white light to specific wavelengths in the blue green spectrum ( 415 nm and 540 nm ) .\nnbi thereby capitalizes on the peak absorption of hemoglobin and has the ability to accentuate visualization of the mucosal vasculature 1 .\nproposed clinical applications of nbi include endoscopic evaluation of barrett s esophagus and endoscopic diagnosis of colorectal polyps .\nstudies of nbi in endoscopic inspection of barrett s esophagus have demonstrated high sensitivity of nbi in detection of barrett - associated high grade dysplasia 2 , and the ability of nbi to detect dysplasia in a higher proportion of patients with fewer biopsy samples compared with standard white light endoscopy 3 . with respect to colorectal polyps ,\nan nbi - based classification scheme has been developed which may accurately distinguish adenomatous from hyperplastic polyps 4 , although it is not certain that use of nbi improves polyp detection rates 5 \n 6 \n 7 . despite data regarding potential gastrointestinal endoscopic applications of nbi , the degree to which nbi use has been adopted into clinical practice\nlegitimate questions exist regarding the degree to which efficacy of nbi as demonstrated in clinical studies will translate into effective use of nbi in actual practice 8 .\nthe aim of this study , therefore , was to prospectively define the rate of nbi use among patients referred to a large group endoscopy practice for diagnostic endoscopy ( esophagogastroduodenoscopy and colonoscopy ) , and to identify procedural factors associated with nbi use .\napproval to conduct this study as a quality assurance protocol was granted by the institutional review board at the study institution .\nthis study was conducted at the endoscopy center of a tertiary care academic center , where both inpatient and outpatient procedures are performed in a hospital - based suite .\neach procedure room is equipped with nbi capability ( 180 series gastroscope or colonoscope , cv-180 evis exera ii video processor , and clv-180 light source ; olympus medical systems , tokyo , japan ) .\neach consecutive esophagogastroduodenoscopy ( egd ) and colonoscopy was directly observed by in - room endoscopy technicians , who assist the endoscopist with equipment setup and when endoscopic accessory use ( i. e. biopsy forceps , polypectomy snare , endoscopic hemostatic device , etc . )\na technician is present in each procedure room for the entire duration of each procedure . for each eligible procedure , the technician documented whether or not nbi was used .\nprocedures performed by the study author were not included ; otherwise all faculty endoscopists were eligible for observation .\nthe following endoscopic procedures were excluded from the analysis : egd or colonoscopy with therapeutic intent , specifically endoscopic dilation , endoluminal stent maneuvers , or delivery of endoscopic hemostatic therapy ; egd for nasoenteral or percutaneous feeding tube placement ; balloon- or spiral - assisted small - bowel enteroscopy ; endoscopic retrograde cholangiopancreatography ; egd with endoscopic ultrasound ; ileoscopy and pouchoscopy .\nfollowing completion of the 2-week observational study period , operative reports including reports generated by olympus endoworks software and dictated operative notes were manually reviewed by the study author , who was not blinded to study design or intent .\nthe following data were extracted : procedure type , procedure indication , identification of attending endoscopist , trainee involvement , patient type ( inpatient versus outpatient ) , procedure start time ( a.m. vs. p.m. ) , sedation - type ( endoscopist - directed conscious or deep sedation vs. monitored anesthesia care with anesthesia staff support ) ; performance of endoscopic polypectomy , either by snare or forceps biopsy ; performance of endoscopic tissue biopsy for intent other than polypectomy .\nextracted data were stored in a microsoft excel spreadsheet , and statistical analyses were performed using jmp 10.0.0 software ( sas institute , cary , nc , usa ) .\nthe chi - squared or fisher s exact test was used for comparison of categorical variables . two - sided p values of < 0.05 were considered statistically significant .\nduring the two - week observational study period in july august 2013 , data regarding nbi use were recorded for 318 elective endoscopic procedures , consisting of 106 egds and 212 colonoscopies .\nthe most common indications for egd were evaluation of abdominal pain / dyspepsia ( 22 % ) and evaluation of gastroesophageal reflux disease ( 19 % ) .\nadditional indications included evaluation of weight loss , anemia or suspected gastrointestinal bleeding , and diarrhea . the most common indication for colonoscopy was screening / surveillance for colorectal cancer ( 56 % ) .\nadditional indications included evaluation of suspected or established inflammatory bowel disease , anemia or suspected gastrointestinal bleeding , and diarrhea .\nthis included use of nbi in 4.7 % ( 5/106 ) of egds and 7.5 % ( 16/212 ) of colonoscopies ( p = 0.47 for comparison ) .\nno difference in rate of nbi use was found when comparing egd with or without biopsy ( 5.5 % [ 3/55 ] vs. 3.9 % [ 2/51 ] ; p = 1 ) , or when comparing colonoscopy with or without biopsy ( 10.5 % [ 8/76 ] vs. 5.9 % [ 8/136 ] ; p = 0.28 ) .\nnbi use was significantly higher in colonoscopy with polypectomy when compared with colonoscopy without polypectomy ( 13 % [ 10/77 ] vs. 4.4 % [ 6/135 ] ; p = 0.03 ) ( fig . 1 ) . \n\nrates of narrow band imaging ( nbi ) use for all study procedures , esophagoduodenoscopy ( egd ) with and without biopsy , colonoscopy with and without polypectomy .\n, there was no association between patient type ( outpatient vs. inpatient ) , procedure start time , sedation type , or trainee involvement and use / non - use of nbi . for both egd and colonoscopy ,\nthere was no association between procedure indication and use / non - use of nbi .\nnbi use was observed in zero of seven egds with a documented primary procedural indication of screening for or surveillance of barrett s esophagus .\nnbi use was observed in 2 of 9 ( 22 % ) colonoscopies with a documented primary indication of surveillance in the setting of chronic ulcerative colitis .\nno use of an alternative imagine modality , such as methylene blue chromoendoscopy or high magnification endoscopy was described in any operative report .\nobserved endoscopic procedures were performed by 23 faculty endoscopists , with a procedure volume ranging from 1 to 58 per endoscopist during the 2-week study period .\nthe rate of nbi use ranged from 0 to 100 % of procedures per endoscopist .\nafter excludsion of endoscopists who performed fewer than five endoscopies during the study period , the rate of nbi use for the remaining 15 endoscopists ranged from 0 to 23 % . there was a significant difference in rate of nbi use ( p < 0.01 for overall comparison ) amongst these 15 endoscopists .\nnbi use among the 5 highest volume endoscopists ranged from 0 to 16 % . among cases with\nobserved nbi use , photodocumentation of nbi use was present in 24 % ( 5/21 ) of operative reports .\nthis observational study detected use of nbi in 6.6 % of elective endoscopic procedures .\nthe highest rate of nbi use was observed in colonoscopies with polypectomy ( 13 % ) , and this rate was significantly higher than that observed in colonoscopies without polypectomy .\nthis study also detected a significant difference in the rate of nbi use in global comparison of individual endoscopists .\nspecific factors that influence the adoption of nbi use into routine practice by individual endoscopists were not examined in this study .\nendoscopists were not asked to self - report nbi use and were not informed of the study .\nthe study was designed in this fashion to avoid the potential of a hawthorne effect , wherein performance may be influenced in subjects who are aware that they are being observed .\nthe endoscopists were blinded to the study , making the study design and findings unique .\na survey of european university hospitals reported use of nbi or alternative commercial enhanced - imaging technology in 67 % of institutions in the evaluation of barrett s neoplasia 9 , but did not report a per - case use rate . in the current study , there was no a priori hypothesis regarding the rate of nbi use expected in this observational study , as there are limited standard recommendations or guidelines for routine nbi use in diagnostic endoscopy , and existing guidelines are open to flexible interpretation .\nfor instance , the american gastroenterological association medical position statement on barrett s esophagus suggests that chromoendoscopy or electronic chromoendoscopy is not necessary in the routine endoscopic surveillance of barrett s esophagus , but may be helpful in guiding biopsies for patients with dysplasia or visible mucosal abnormalities 10 .\nthe rate of nbi use in this study can therefore not be subjectively designated as high or low , but instead serves as a baseline metric in this study setting against which future nbi use can be measured .\nadoption of nbi use in routine diagnostic endoscopy may have implications for application of future enhanced - imaging technologies . in the hands of the endoscopist\nno additional equipment is required other than an existing video monitor and nbi - equipped scope and processor .\nan endoscopist can toggle between nbi and standard white light literally in seconds , without use of additional endoscopic devices , accessories , or medications . and while there may be a learning curve for interpretation of nbi images 11 \n 12 , endoscopist interpretation of endoluminal nbi images would seem less a departure from white light endoluminal images than interpretation of images generated by other optical techniques , such as endomicroscopy , that focus on cellular structures . based on these criteria , one would speculate that adoption and use of imaging technologies requiring additional equipment or capital investment , additional time with respect to procedure duration , and/or increasingly complex image analysis would be lower than that for nbi . finally , it is worthwhile to note that documentation of nbi use was uncommon .\nphotodocumentation of nbi use was provided in 24 % ( 5/21 ) of operative reports from cases in which nbi use was observed .\nfuture consideration may be warranted as to whether documentation guidelines should exist for procedural use of nbi or other adjunct imaging modalities .\nan american society of gastrointestinal endoscopy preservation and incorporation of valuable endoscopic innovations ( pivi ) statement on real - time endoscopic assessment of histology of colon polyps suggests that lesion photocumentation is necessary if a resect - and - discard strategy is to be implemented 13 . while extending the study duration to increase sample size would increase statistical power and eliminate the possibility of type ii error in examining factors associated with nbi use , the study as completed is likely to have strong internal validity , in that the observed range of endoscopic procedures during the 2-week time period is likely to offer an accurate representation of the range of endoscopic practice in this setting\n. it may not be possible , however , to generalize the study findings to other institutions or endoscopy settings which may have differing practice patterns .\ninstances of nbi use may not have been documented if not observed or not recognized by the endoscopy technician .\nan alternative would have been to video record the entire procedure for subsequent review ; however maintenance of adequate blinding with this approach would be challenging .\ndocumented cases of nbi use can not distinguish between intentional and unintentional nbi use for instance , if the endoscopist had inadvertently pressed the button on the scope handle for application of nbi when he / she had intended instead to press the button for image capture . in addition , there was limited heterogeneity in some of the procedural variables ( e. g. trainee involvement ) to adequately assess for potential association with nbi use / non - use .\na post hoc survey of participating endoscopists might offer insight as to whether their opinions on the role of nbi match their actual practice , but has no bearing on the aim of this study , which was to objectively document rate of nbi use . in summary ,\nadditional large - scale prospective data are needed to assess the magnitude of impact of nbi on routine endoscopic practice .", "answer": "background and study aim : narrowband imaging ( nbi ) is an enhanced endoscopic optical technique which filters white light and accentuates imaging of the mucosal vasculature . \n potential clinical applications of nbi include endoscopic inspection of barrett s esophagus and endoscopic diagnosis of colorectal polyps . \n the degree to which nbi use has been adopted into clinical practice is unknown . the study objective was to identify the rate of nbi use in patients undergoing elective esophagoduodenoscopy ( egd ) and colonoscopy , and to identify procedural factors associated with nbi use . \n \n methods : elective endoscopic procedures were prospectively observed over a 2-week study period . \n nbi use during diagnostic egd or colonoscopy was recorded in blinded fashion . \n \n results : nbi use was observed in 6.6 % ( 21/318 ) of procedures , including 4.7 % ( 5/106 ) of egds and 7.5 % ( 16/212 ) of colonoscopies . \n there was no difference in rate of nbi use when comparing egd with or without biopsy , or when comparing colonoscopy with or without biopsy . \n nbi use was significantly higher in colonoscopy with polypectomy compared with colonoscopy without polypectomy ( 13 % [ 10/77 ] vs. 4.4 % [ 6/135 ] , p = 0.03 ) . \n nbi use varied significantly among endoscopists . \n there was no association between patient type ( outpatient vs. inpatient ) , procedure start time , sedation type , or trainee involvement and use / non - use of nbi . procedural documentation of nbi use was limited . \n \n conclusions nbi use was observed in 6.6 % of elective endoscopic procedures and was highest in colonoscopies with polypectomy . \n rate of nbi use varied significantly among endoscopists . \n additional studies are needed to assess the magnitude of impact of nbi on routine endoscopic practice .", "id": 406} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin 1978 , primary health care was seen as the solution to the inadequate illness management systems that had developed throughout the world .\nit was hoped that phc would address some of the major inequalities in health that were observed by a balanced system of treatment and disease prevention . the world health organization ( who ) envisaged that phc would take place as close as possible to where people live and work and be the first element of a continuing health care process .\nadditionally , health service collaboration and multi - professional partnerships were expected to replace professional boundaries and competition . to sum up\n, phc used family physician as the most important ways to increase equitable access and utilization of public health services . in any case , family physician , with the key elements of first contact , comprehensiveness , continuity , and coordination of patient care , is central to the health of any health care system .\nrecent government initiatives are supporting general practice to deliver health care through a variety of means and personnel .\nthese initiatives have included expanding the roles of nurses in general practice and enabling better access to allied health services through general practitioners ( gps ) .\nevidence clearly indicates the effectiveness of teams in improving the outcomes , especially in chronic disease .\nnow , people in most of the countries use professional and educated nurses [ called nurse practitioner ( np ) ] besides family physician or are under their supervision for diagnosis , treatment , and specifically health education of the family . in accordance with the international council of nurses definition ,\n a nurse practitioner is a registered nurse who has acquired the expert knowledge base , complex decision - making skills , and clinical competencies for expanded practice , the characteristics of which are shaped by the context and/or country in which s / he is credentialed to practice .\n the royal college of nursing ( rcn ) defines an np as a registered nurse who has undertaken a specific course of study of at least first - degree ( honors ) level and who : \n makes professionally autonomous decision , for which he or she is accountable;works collaboratively with other health care professionals;provides counseling and health education;screens patient for disease risk factors and early signs of illness ; andhas the authority to admit or discharge patients from their caseload , and refers patients to other health care providers as appropriate . \n \nmakes professionally autonomous decision , for which he or she is accountable ; works collaboratively with other health care professionals ; provides counseling and health education ; screens patient for disease risk factors and early signs of illness ; and has the authority to admit or discharge patients from their caseload , and refers patients to other health care providers as appropriate . in new reform toward family physician in iran ,\nthere is not enough attention toward nurses , their services , and specifically their role in education and counseling .\naccording to the health - for - all goals , the central concern of nurses in primary care should be the prevention of the disease by educating individuals and families on healthy lifestyles , and teaching community health workers and traditional birth practitioners to carry out many of the functions that nurses themselves have normally performed .\nwhereas a big part of the family physician program has not been realized in iran yet ( especially in big cities with a population of over 20,000 ) , most graduate nurses are now working in the school of nursing and midwifery , hospitals , and ambulatory clinics with limited responsibilities .\nin addition , most graduate nurses in our community can play an important role in preventing medicine and family physician team . consequently , in spite of their ability and capacity , they have a brief role in our family physician team & their job description .\nthe main goal of this study was to review the role and situation of nps in the new reform for better use of their capabilities in health care services .\nthis is a qualitative , comparative ( role of nurses in family physicians team ) , and cross - sectional study that was carried out with triangulation method in three stages in 2011 . in the first stage , we conducted a literature review to design a conceptual framework .\nthe second stage was a comparative study on four countries that had great experiences in these two fields ( family physician reform and nps ) and included usa , uk , austria , and canada , based on purposive sampling . in the third stage ,\nall experts were completely familiar with the health system and had academic and research experiences in nursing education system in iran .\nthe survey on health systems in different countries indicates that many of the health sectors have begun their reforms with two main goals , including quality improvement and cost limiting .\nfamily physician and referral system are among the few options that can maintain and even upgrade the quality of services , reducing the costs simultaneously . as each health system in each country\nhas its specific referral system , iran is now on the verge of implementing a best fit referral system reform .\nso , it is crucial to well define the roles of each component , such as nurses , in this system . in the united states ,\nnps are licensed by the state in which they practice , and have a national board certification ( usually through the american nurses credentialing center or american academy of nurse practitioner ) .\nmost nps specialize in a particular field of medical care , and there are as many types of nps as there are medical specialties .\nnps provide high - quality , cost - effective individualized care that is comparable to the health care provided by the physicians , and np services are often covered by insurance providers .\nrole of nurses in some organizations in canada , the nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration .\nthen , they are allowed to prescribe drugs , and lab and other diagnostic tests .\nhaving access to patient medical record , nps can reduce unnecessary visits . according to the standards of practice for nps , the college of nurses of ontario states that they offer the full scope of primary health care practice , including consultation with physicians or other health care professionals when the client requires care beyond the nps scope of practice . \nfurther , they are accountable for establishing a consultative relationship with a physician and consultation occurs with a family physician ; however , nps may consult with a specialist physician , if appropriate to the situation and practice setting .\nno legislative or regulatory deterrent related to the scope of practice exists for the nps to refer to specialist physicians . in austria , nurses in nursing home and maternity do some of the medical procedures under the supervision of physicians .\nthese nurses are educated , and can treat , inject drugs , and request for some diagnostic tests for their patients . in the united kingdom ,\nthe gps monopoly on primary care has been broken by nurse - led services , including nhs direct , which provides 24-h health advice by telephone , and nhs walk - in centers , which treat minor illness and injury .\npractice nurses and nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases such as asthma , diabetes , and coronary heart disease . in england and wales ,\nthe role of the nps had evolved from that of undertaking traditional , medically prescribed nursing tasks in a treatment room to undertaking screening activities and health assessments of new patients , with over 50% of the nps managing chronic disease clinics .\nsix experts in two panels were asked to confirm the role of nurses in family physician reform .\nthey suggested that special courses are needed to empower our graduated nurses for their new rules .\nmeanwhile , using nps as substitution of gps does not seem to be logically correct due to the gps workload and the social and cultural background in iran .\nthe survey on health systems in different countries indicates that many of the health sectors have begun their reforms with two main goals , including quality improvement and cost limiting .\nfamily physician and referral system are among the few options that can maintain and even upgrade the quality of services , reducing the costs simultaneously . as each health system in each country\nhas its specific referral system , iran is now on the verge of implementing a best fit referral system reform .\nso , it is crucial to well define the roles of each component , such as nurses , in this system .\nin the united states , nps are licensed by the state in which they practice , and have a national board certification ( usually through the american nurses credentialing center or american academy of nurse practitioner ) .\nmost nps specialize in a particular field of medical care , and there are as many types of nps as there are medical specialties .\nnps provide high - quality , cost - effective individualized care that is comparable to the health care provided by the physicians , and np services are often covered by insurance providers .\nrole of nurses in some organizations in canada , the nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration .\nthen , they are allowed to prescribe drugs , and lab and other diagnostic tests .\nhaving access to patient medical record , nps can reduce unnecessary visits . according to the standards of practice for nps , the college of nurses of ontario states that they offer the full scope of primary health care practice , including consultation with physicians or other health care professionals when the client requires care beyond the nps scope of practice . \nfurther , they are accountable for establishing a consultative relationship with a physician and consultation occurs with a family physician ; however , nps may consult with a specialist physician , if appropriate to the situation and practice setting .\nno legislative or regulatory deterrent related to the scope of practice exists for the nps to refer to specialist physicians . in austria , nurses in nursing home and maternity do some of the medical procedures under the supervision of physicians .\nthese nurses are educated , and can treat , inject drugs , and request for some diagnostic tests for their patients . in the united kingdom ,\nthe gps monopoly on primary care has been broken by nurse - led services , including nhs direct , which provides 24-h health advice by telephone , and nhs walk - in centers , which treat minor illness and injury .\npractice nurses and nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases such as asthma , diabetes , and coronary heart disease . in england and wales ,\nthe role of the nps had evolved from that of undertaking traditional , medically prescribed nursing tasks in a treatment room to undertaking screening activities and health assessments of new patients , with over 50% of the nps managing chronic disease clinics .\nsix experts in two panels were asked to confirm the role of nurses in family physician reform .\nthey suggested that special courses are needed to empower our graduated nurses for their new rules .\nmeanwhile , using nps as substitution of gps does not seem to be logically correct due to the gps workload and the social and cultural background in iran .\naccording to the who , in most countries , nurses are the most important group of health workers in terms of numbers , closeness to people and their health problems , and understanding of community needs . there is still debate in nursing and medical circles about what the focus of their role should be .\nfor example , lauder , sharkey , and reel suggest that nps and gps in rural and remote areas should be interchangeable and that the focus should be on the competency of the person delivering care rather than the right of one discipline ( medicine ) to perform a particular role .\nin contrast , campbell believes that public acceptance of nurses as gp substitutes would be poor , and therefore suggests that a better role for nurses in primary care would be health education and illness prevention . on the other hand , in our country ( iran ) until now , nurses have not got a competent role in health sector reform .\ngiven that consumers have limited understanding of phc , it is not surprising they do not articulate confidence in nps acting autonomously but rather as complementary to gps , perhaps undertaking initial assessment for triage purposes and providing ongoing management , education , and support under the gps delegation .\nthey would also like them to be family oriented and holistic in their practice , supporting their emotional and social needs in the context of their family lives .\nit means that any effort to change nurses roles in health care services should accompany with some social and cultural changes toward their competencies . in iran , whereas a noticeable reform toward family physician is going on , redefining nurses role is essential .\nthey can perform more active roles in associating with gps in the clinics of family physicians , both in urban and rural areas , even with higher degrees of autonomy .\ntheir competencies for case management , education , treatment , and follow - up may repair many of the pitfalls we are confronting in health care services .\nof course , if it has to be done , special courses are needed to empower graduated nurses for their new rules .\nmeanwhile , substitution of gps with nps does not seem to be a good suggestion due to gp workload and social and cultural background in iran .\nthus , it can be concluded that in order to achieve the goals of family physicians reform and also utilize the maximum capacity of trained nurses , a fixed and definite place must be considered for them in the gp team to provide their services under the supervision of family physicians .\ntheir active role not only enriches the family physician team , but also might be crucial in patients training , which is currently one of our weaknesses .", "answer": "background : most countries use educated nurses called nurse practitioners ( nps ) besides the family physicians for diagnosis , treatment , and specifically health education of the family . \n the main goal of this study was to redefine the role of nps for better use of their capabilities in the so - called family physician reform in iran.materials and methods : this is a qualitative and comparative study carried out in three stages ( triangulation method ) in 2011 . in the first stage \n , we conducted a literature review to design a conceptual framework . \n the second stage was a comparative study on four countries . in this study , we focused on the role of nps , which in turn helped to redefine this role in the health sector reform of iran . in the third stage , \n two expert panels were involved and the suggested roles were confirmed.results:in the united states , nps are licensed by the state in which they practice and have a national board certification . in canada , nurses involved in clinics should participate in specific training course of diagnosis and management of health care after registration . in austria , \n nurses in nursing homes and maternity do some of the medical procedures under the supervision of the physicians . in the united kingdom , \n nps increasingly substitute for gps in the care of minor illness and routine management of chronic diseases.conclusions:there is still debate in nursing and medical circles about what the focus of the np roles should be . in iran , whereas a noticeable reform toward family physician \n is ongoing , redefining the nurses role is essential . \n they can perform more active roles in associating with gps in the clinics of family physicians , both in urban and rural areas , even with higher degrees of autonomy .", "id": 407} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneonatal intestinal perforation ( nip ) is an extremely rare complication of intestinal hemangioma ( ih ) .\nneonates younger than 30 days and having perforation include more common etiologies such as necrotizing enterocolitis , meconium ileus , and spontaneous idiopathic as well as gastric perforation.1 nip has been associated with mortality rates of 40% to 70%.2 this report presents a rare case of nip resulting from ih .\na 27-day - old male neonate was admitted with low - grade fever , abdominal distension , and bilious vomiting associated with bouts of diarrhea of 2 days duration .\nbaby was a product of full - term spontaneous vaginal delivery with normal prenatal follow - up . before coming to our hospital ,\nthe patient weighed 4.1 kg and was febrile , irritable , and moderately dehydrated .\nplain abdominal radiographs suggested bowel obstruction versus ileus , therefore a barium meal follow through was obtained , which showed persistently dilated jejunal and proximal ileal loops but normal flow of contrast .\ncomputed tomographic scan with intravenous contrast was not done because of family history of allergic reaction to the dye . on the basis of the diagnosis of intestinal obstruction , a decision for exploratory laparotomy was made .\nlaparotomy revealed dense inflammatory adhesions surrounding a solitary hemangioma located at the antimesenteric border 30 cm from the ileocaecal valve and on close inspection a small perforation was seen on one side of the hemangioma , which was sealed by extensive adhesions ( fig .\nother areas of the bowels inspected were normal and resection with primary anastomosis was done . \n\ndilated capillary spaces lined by single layer of endothelium with proliferation of endothelial cells in between .\nhemangiomas of the gastrointestinal tract are rare and account for only 0.05% of all intestinal neoplasms.3 they are commonly found within the small bowel , jejunum being the commonest site and compose 7 to 10% of all benign tumors.3 \n\n4 they have a tendency toward multiplicity , with solitary tumors being extremely rare.3 \n 5 microscopically , ih may be classified as cavernous , capillary , or mixed types , commonest being the cavernous.6 the usual presentation is intestinal bleeding usually insidious presenting as anemia7 or sometimes acute and potentially life threatening.4 other forms of rare presentation include intussusception , obstruction , and perforation.8 \n 9 \n 10 \n ileal perforation is a rare complication of ih in neonates , and so far , only one case has been reported in the literature , by mcgaughey et al,11 who discovered evidence of ileal perforation due to ih while operating on a neonate with intestinal obstruction .\nours is the second reported case of nip due to ih , and what makes it unique is the fact that the hemangioma belonged to the rare capillary type whereas the previously reported case was of the commoner cavernous type .\ndiagnosis in both reported cases , including ours , were made only at surgery for presumed acute intestinal obstruction .\nalthough various causes of nip including the rare ih have been reported , diagnosis can be difficult and exploratory laparotomy has often proved to be the final diagnostic tool .\nalthough a rare cause of intestinal perforation in neonates , ih should be considered in the differential diagnosis .", "answer": "intestinal perforation is an extremely rare complication of hemangioma of the small intestine in the neonatal period . \n this is a case report of a 27-days - old male infant who presented with signs and symptoms of acute intestinal obstruction . \n exploratory laparotomy findings revealed intestinal perforation due to solitary hemangioma in the ileum , which led to obstruction from peritoneal reaction and adhesions . \n there are two reported cases in the literature presenting with ileal perforation in the pediatric age group , but only one previous report mentioned in the neonatal period . because there are other more common causes of perforation in the neonatal period , intestinal hemangioma in spite of its rarity \n should be included in the differential diagnosis .", "id": 408} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 36-year - old japanese man was referred to us for the evaluation of bilateral retinal hemorrhages .\nhe developed an acute vision decrease in his left eye , pain in his right chest area , and headache after he had trekked at an altitude of 4600 m in tibet for 1 week .\nbecause of the illness , he descended 3 days later , and he felt better at that time but the visual impairment remained .\nour examination showed that his visual acuity was 20/20 od and 20/200 os with refractive errors of 0.25 diopters ( d ) od and 0.50 d os measured 3 weeks after the onset of the visual decrease .\nfunduscopic examination revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye [ fig . 1 ] .\nsd - oct ( spectralis , heidelberg engineering , heidelberg , germany ) showed that the macular hemorrhage was in the superficial layer of the retina beneath the inner limiting membrane of the left eye [ fig\nthe thickness of the choroidal layer at the fovea was 530 m od and 490 m os which was thicker than the mean subfoveal choroidal thickness in normal subjects of approximately 300 m in the enhanced depth images obtained by spectralis sd - oct .\nmost recent studies report that the average subfoveal choroidal thickness is 287 m in caucasians of an average age of 50.4 years and 272.6 m in the japanese of an average age of 30.5 years obtained by the enhanced depth imaging of the spectralis sd - oct .\nfundus photograph of the right eye ( a ) and the left eye ( b ) showing multiple intraretinal hemorrhages and a macular hemorrhage in the left eye optical coherence tomographic images at the first visit .\nthe choroidal layers ( white arrowheads ) are thick in both eyes ( a : right eye , b : left eye ) .\na macular hemorrhage located in the superficial retina beneath the inner limiting membrane of the left eye ( white arrow ) can be seen\nindividuals with acute mountain sickness present with lethargy , nausea , headache , insomnia , anorexia , and disorientation .\nthe proposed mechanism for the symptoms of acute mountain sickness is respiratory alkalosis from hyperventilation and increased cerebral blood flow . in hace , there is a breakdown of the blood \nhowever , hace can lead to long - lasting severe neurological and psychiatric disorders and even death in some cases .\nwiedman and tabin examined 40 climbers who had ascended to altitudes of over 4870 m whether they developed signs of har , symptoms of acute mountain sickness , and clinically signs of hace .\nthus , they concluded that when advanced har is recognized , treatment should be initiated for hace with oxygen , steroids , or diuretics , and immediate descent to prevent further progression of hace . a pronounced increase in retinal blood flow in mountaineers with retinal hemorrhage and\ndilated epipapillary network has been detected with heidelberg retina flowmeter after acute hypoxic stress at high altitudes .\nthe increase in retinal blood blow and cerebral blood flow under hypoxic conditions may also be associated with an increase in choroidal blood flow resulting in an increase in choroidal thickness .\nthe pathogenesis of the increased choroidal thickness may be similar to that of hace , namely a breakdown of the blood \nit is difficult to draw strong conclusions from a single case ; however , we suggest that measurements of the choroidal thickness may be useful in evaluating the status of hace\n. currently , data are not available from population - based studies on the normal values for the choroidal thickness of a large number of caucasians or asians .\nfurther studies are needed to evaluate the choroidal thickness in mountaineers with acute mountain sickness .", "answer": "we report a case of high - altitude retinopathy with increased choroidal thickness detected by spectral - domain optical coherence tomography ( sd - oct ) . a 36-year - old japanese man developed an acute vision decrease in his left eye after he had trekked at an altitude of 4600 m in tibet for 1 week . \n his visual acuity was 20/20 od and 20/200 os with refractive errors of 0.25 diopters ( d ) od and 0.50 d os 3 weeks after the onset of the visual decrease . \n funduscopic examinations revealed multiple intraretinal hemorrhages bilaterally and a macular hemorrhage in the left eye . \n sd - oct showed that the thickness of choroidal layer at the fovea was 530 m od and 490 m os which is thicker than that in normal subjects of approximately 300 m . \n we suggest that the increase in the retinal blood flow under hypoxic conditions may be associated with an increase in the choroidal blood flow resulting in an increase in choroidal thickness .", "id": 409} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n( itbl ) are \n often used as synonyms for hilar or intrahepatic diffuse bile duct strictures , \n necrosis , ecstasies , or dilatations ( see figure 1 ) [ 1 , 2 ] .\nthe reported \n incidence of itbl after olt varies between 1.4% and 20% [ 35 ] .\nthis complication encounters for major morbidity and mortality , creates high \n costs , and aggravates organ shortage [ 7 , 8 ] .\na recent study on 1113 liver transplant patients showed \n no relevant donor or recipient risk factor of itbl .\nthere are only \n two studies evaluating the impact of chemokine receptors ( ccr ) on the \n development of itbl [ 6 , 9 ] . in moench 's study on 146 olt patients ccr-532 mutation\nwas evaluated and correlated \n with a significant increased incidence of itbl . a recent study on \n 137 pediatric liver transplants failed to show an association between ccr-532 and biliary complications . \n\nccr-532 is a single base - pair deletion of ccr-5 that \n leads to a nonfunctional receptor .\nthe clinical impact of this \n mutation was first described for homozygous ccr-532 caucasians being highly resistant to hiv-1 \n infection .\nif there was an immunological cause for itbl , a \n nonfunctional ccr might be relevant for this complication .\nexperimental studies correlated a \n nonfunctional ccr-5 with less acute rejection episodes in lung , heart and islet cell transplantation .\nthe aim of this study was to re - examine a \n correlation of ccr-532 genotype with the susceptibility of itbl \n within our patients .\nall patients were transplanted at the transplant center of the \n humboldt university of berlin between 03/2002 and 03/2005 and were included \n during routine follow - up examination .\n11 patients with the established diagnosis of itbl , that were transplanted \n earlier than 03/2001 , were selectively included into this study due to the low \n incidence of itbl of only 4.0% within our patients .\nthe diagnosis of itbl was \n made within the first year after transplantation in 82% of the patients .\nthe \n following demographic data were extracted from the hospital records and \n evaluated : age , gender , underlying liver disease , blood group , child - pugh score \n ( cps ) , model for end stage liver disease score ( meld score ) , initial \n immunosuppression , cytomegalovirus infection ( cmv ) , hla match , donor age and \n gender , donor serum sodium , cause of brain death and length of stay on \n intensive care unit ( icu ) prior to organ harvesting .\n154 patients received a \n cadaver graft , 15 patients received a graft from a living donor .\nitbl was defined as nonanastomotic intra- or \n extrahepatic biliary strictures without any history of hepatic artery \n complications , abo , incompatibility or other known causes of bile duct damages . \n in all cases patency of the hepatic artery\nrecurrence \n of primary biliary cirrhosis ( pbc ) or primary sclerosing cholangitis ( psc ) and \n vanishing bile duct syndrome were ruled out in all cases by liver biopsy . \n\ndiagnosis of itbl was always established with endoscopic retrograde \n cholangiography or percutaneous transhepatic cholangiography .\nall \n genotype analyses were performed at the johannes gutenberg university of mainz , \n department of transplantation surgery . for analysis of the ccr-5 genotype , \n\ngenomic dna was prepared from 200 l peripheral blood using the qiaamp dna blood \n kit ( qiagen , cologne , germany ) .\n2.5 l of dna were amplified by pcr using the \n following ccr-5 specific primers : ccr - sense , 5-caaaaagaaggtcttcattacacc-3 \n and ccr-5-antisense , 5-cctgtgcctcttcttctcatttcg-3. the pcr mixture was \n composed of 2.5 l 10 x pcr buffer ( roche molecular systems , \n mannheim , germany ) , 0.5 l of 12.5 mmol / l dntp ( peqlab , erlangen , \n germany ) , 2.5 l of each sense and antisense primer ( 10 mol / l ) , and 1.25 u amplitag dna polymerase \n ( roche molecular systems ) in a total volume of 25 l .\nforty pcr cycles were run on a genius \n thermocycler ( techne , cambridge , uk ) , using the following temperature profile : \n initial denaturation , 94c 3 minutes ; amplification , 94c 1 minute , 64c 1 \n minute , and , 72c 1 minute ( 40 cycles ) ; terminal elongation , 72c 9 minutes .\nthe size \n of the wild - type product was 189 base pairs ( bp ) , and the ccr-532 allele yielded a product of 157 bp .\ndescriptive statistics \n were used to summarize the donor and recipients characteristics . for \n independent variables , cross tabulations and chi - square tests were performed . \n\nnonparametric variables were evaluated with fisher 's exact test , and asymptotic \n significance was calculated .\nall \n calculations were performed in association with the department of biometrical \n medicine of the humboldt university of berlin .\na total \n number of 169 liver transplant recipients were available for genotyping and \n complete data analysis .\ngender and age were equally distributed between \n wild - type group ( wt / wt ) and heterozygous ccr-532 group ( wt/32 ) .\nthe observed genotype \n frequency was as expected assessed by hardy - weinberg equilibrium in the study \n population .\nthere were no differences between wt / wt group and wt/32 group regarding to cps score , meld score or \n blood group ( table 1 ) .\nthere were \n no statistical significant differences in the composition of underlying liver \n disease of group wt / wt and wt/32 .\ninitial \n immunosuppression was tacrolimus based in 82.6% in the wt / wt group compared to \n 84.8% in the wt/32 group .\ncmv infection \n that demanded ganciclovir treatment was present in approximately 30% in the \n wt / wt and wt/32 group and in both homozygous patients .\ndonors of group 32/32 were younger ( 35.7 years versus 46.5 years and \n 48.5 years ) .\nmmol / l in the wt/32 group and 155.5 mmol / l in the 32/32 group .\ndata of causes of brain death and \n length of stay on the icu prior to organ harvesting are shown in table 2 .\nincidence \n of itbl was 11.2% in this study due to the selection of patients with itbl that \n were additionally included into this evaluation .\nhomozygous 32 patients developed no itbl compared to 11.2% \n and 12.1% of homozygous wild - type patients and heterozygous patients , \n respectively .\nthe rate of retransplantation was 3.0% in both wt / wt and wt/32 group ( see table 3 ) .\nretransplantation of \n the heterozygous patient was indicated due to chronic ductopenic rejection \n following olt for psc . in the wt / wt group ,\nthe \n problem of genetic association studies and complex clinical syndromes or \n diseases must be addressed .\none can always question the usefulness of these \n studies that are often even small in sample size .\n, it seems important to undertake \n replication studies for reported associations between genetic polymorphisms and \n diseases , especially in diseases of major clinical importance . in this \n study ,\nthe distribution of heterozygous 32 and homozygous 32 mutation was very consistent with the \n published data of the global distribution of this gene polymorphism [ 10 , 16 ] .\nheterozygous and homozygous genotypes occur \n in caucasian population in 15%20% and 1% , respectively .\nthis seems \n important due to the small number of patients included in this study and the \n possible bias by including selected patients with the diagnosis of itbl into \n the study cohort . despite \n increasing success rates in clinical olt over the past decades\n, itbl remains a \n major cause for recipient morbidity and mortality [ 15 ] .\nup till \n today , only risk factors for itbl could be identified in various clinical \n studies .\nthe length of cold ischemic time was correlated with the development \n of itbl [ 14 ] .\nimmunological causes seem to play only a minor role in the pathogenesis of \n itbl .\ndescribed a single base - pair deletion in the coding region \n of the chemokine receptor-532 , ccr-532 , to be a significant risk factor for the \n development of itbl . in moench 's study on 146 olt patients ccr-532 was a significant risk factor for itbl \n ( incidence of itbl in ccr-532 patients was 30% versus 11.7% in ccr-5 \n wild - type patients ) and was correlated with a decreased survival rate after \n olt .\nthe different incidence of itbl of the study by \n moench and this study may be a reason for the different findings , even though \n both investigators used the same definition of itbl .\ndonors were younger in \n this study with 38.2 16 \n ( non - itbl patients ) and 42.9 17 ( itbl ) \n versus 46 14 \n ( non - itbl ) and 52 14 ( itbl ) \n in moench 's study . however , cold ischemic time was shorter in moench 's \n investigation ( 564 minutes ( itbl ) and 538 minutes ( non - itbl ) versus 637 minutes ( itbl ) and \n 558 minutes ( non - itbl ) ) .\nthe use of arterial back table perfusion was also \n routinely done for all organs that were harvested by a team of our own . \n\nanalyzed ccr-532 polymorphism in 137 pediatric patients but \n showed no correlation with biliary complications .\nthe incidence of \n itbl varies between 1.4% and 20% according to the literature , which might be a \n problem of different definition of this disease [ 35 ] .\nthe rate of itbl in our olt \n patients ( 2100 patients between 1988 and 2004 ) is 4.0% . in the presented study \n on 169 olt patients\nthe overall incidence of itbl was 11.7% , but only due to a \n selective inclusion of patients with the established diagnosis of itbl .\nthis \n practice of patient recruitment may be criticized , but we think it is justified \n according to our low incidence of itbl .\nitbl rate in ccr-532 patients was virtually equal to the one in \n ccr-5 wild - type patients .\nno statistically significant differences regarding \n itbl or retransplantation were observed . why would \n ccr-532 mutation promote the development of itbl ?\nccr-532 is a 32-base - pair deletion within the \n coding region of ccr-5 , which results in a frame shift and generates a \n nonfunctional receptor . \n\nhomozygous expression of ccr-532 is associated with a reduced risk of \n asthma and with a reduced severity of rheumatoid arthritis [ 17 , 18 ] , \n multiple sclerosis [ 19 , 20 ] , and primary biliary cirrhosis ( pbc ) . in other words ,\nthe nonfunctional nature of \n ccr-532 protects the individual from autoimmune \n diseases where ccr-5 seems to play a central pathophysiological role .\nthese \n data do not backup the theory , that immunological risk factors are dominant in \n the development of itbl .\nlikewise , a correlation of a reduced survival rate \n with ccr-532 would not be consistent to the literature , \n where ccr-532 mutation is associated with an increased \n survival in renal , lung , heart and islet \n cell transplantation .\nin contrast \n to those findings , ccr-532 is strongly associated with an increased \n severity of psc .\npatients suffering from psc have been \n described as carrying a higher risk for itbl , with a reported significantly \n increased incidence of 15.8% to 25% [ 1 , 8 , 23 ] .\nanother study reported psc as the only \n independent risk factor for itbl with an incidence of 31% compared with 9% of the \n control group .\nhowever , \n the problem of differentiation between itbl and recurrence of psc must be addressed . \n\nrecurrence rates of 8.6% to 25% were described for psc after olt [ 2527 ] .\nthe diagnose of recurrence \n of psc is based on cholangiographic findings of intrahepatic , hilar and/or \n exrahepatic strictures , duct irregularities and on the histopathological picture \n of fibrous cholangitis and/or fibro - obliterative lesions with or without \n ductopenia , biliary fibrosis , or biliary cirrhosis .\nmost of these findings are neither \n pathognomonic for either recurrence of psc nor itbl .\nall patients with itbl in this study \n underwent percutaneous liver biopsy , and our pathologists ruled out psc \n recurrence .\nsince two \n of three studies failed to show an association between itbl and ccr-532 gene polymorphism , a general recommendation \n for screening of olt patients for ccr-532 does not seem to be justified .", "answer": "it has been shown that certain chemokine receptor polymorphisms may correspond to certain complications after organ transplantation . \n ischemic - type biliary lesion ( itbl ) encounters for major morbidity and mortality in liver transplant recipients . \n so far , the exact cause for itbl remains unclear . \n certain risk factors for the development of itbl like donor age and cold ischemic time \n are well described . in a previous study , a 32-nucleotide deletion of the chemokine receptor-532 ( ccr-532 ) \n was strongly associated with the incidence of itbl in adult liver transplantation . \n this study re - evaluates the association of ccr-532 gene polymorphism and the incidence of itbl . \n 169 patients were included into this retrospective \n analysis . \n 134 patients were homozygous for wild - type ccr-5 , 33 patients heterozygous , and 2 patients were homozygous for ccr-532 mutation . \n there were no major differences in donor or recipients demographics . \n no association was found between ccr-532 mutation and the development of itbl . \n we conclude that ccr-532 is no risk factor for the development of itbl in our patient cohort .", "id": 410} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nNickel-Catalyzed Cross-Electrophile Coupling of Aryl Chlorides with Primary Alkyl Chlorides\n\nPaper sections:\n\nCross-electrophile coupling has rapidly become an important approach to the synthesis of Csp2-Csp3 bonds,1 but engaging less reactive C-Cl bonds, outside of activated systems2 or intramolecular reactions,3 has proven challenging. Indeed, unactivated C-Cl bonds are well-tolerated functional groups4 in cross-electrophile coupling methods (Scheme 1).5,6 The ability to cross-couple with organic chlorides is valuable for several reasons \u2013 first, organic chlorides are more abundant than organic bromides or organic iodides;7 second, the low reactivity of the C-Cl bond allows it to be introduced early in a synthesis and later diversified.8,9,10
The central challenge presented by C-Cl bonds in cross-electrophile coupling is the need for higher reactivity without sacrificing selectivity (Scheme 1). While the homodimerization of alkyl chlorides11 and aryl chlorides8c has been reported, no general cross-selective approach has yet been found.12 Recently, Zhang reported couplings of a variety of aryl chlorides, but only with an excess of ClCF2R reagents.13 Several groups have reported on the coupling of aryl chlorides with alkyl bromides14 or tertiary alkyl oxalate esters.15 However, the coupling of chlorobenzene with a simple alkyl bromide provided less than 25% yield of cross-coupled product.14a Switching to an alkyl chloride further diminishes selectivity and yield using our standard conditions (Scheme 1).16
Based upon our proposed mechanism for the coupling of aryl iodides with alkyl iodides,17\u201318,19, overcoming this dual reactivity-selectivity challenge requires a catalyst that selectively reacts with the Ar-Cl over the Alkyl-Cl, yet can slowly generate an alkyl radical from the Alkyl-Cl starting material. Herein we show that this can be accomplished through the use of salt additives to maintain a very low, steady-state concentration of an alkyl bromide/iodide and a uniquely selective pyridine-2,6-bis(N-cyanocarboxamidine) (PyBCamCN)20,21 ligated nickel catalyst (Scheme 1).
During reaction development, we observed a strong synergistic effect between the catalyst and the presence of substoichiometric amounts (10\u201330 mol%) of bromide or iodide (Table 1 and Supporting Information Figures S1, S4-S7). While no catalysts were found that provided high yields of product in the absence of bromide or iodide, high selectivity could be achieved in reactions with PyBCamCN ligand and NiBr2(dme) or NiI2\u20224H2O; and in reactions with PyBCam ligand and NiBr2(dme) (Table 1, bold-faced entries). Reactions with bipyridine (bpy) or pyridine 2-carboxamidine (PyCam) ligands, which are optimal for the coupling of aryl bromides with alkyl bromides,20,22 favored formation of aryl dimer products (bpy) or hydrodehalogenated arene (PyCam) without consuming the alkyl chloride. Reactions with terpyridine (tpy), which is useful for the dimerization of alkyl halides,23 converted alkyl chloride to dimeric and hydrodehalogenated products without consuming aryl chloride. In contrast to tpy, reactions with 4,4\u2032,4\u2033-tri-tert-butyl-2,2\u2032:6\u2032,2\u2033-terpyridine (tpy\u2034), which is useful in Negishi cross-coupling reactions of alkyl halides,24 consumed both substrates but formed approximately 1:1:1 product/alkyl dimer/aryl dimer.25 See also Chart S1 in the Supporting Information.
Routine optimization with PyBCam and PyBCamCN demonstrated that PyBCamCN was superior, that reactions were best conducted at 60\u201380 \u00b0C, and that a variety of iodide and bromide additives provide similar results.25 Reactions with bromide additive provided the highest yields when the alkyl chloride was added slowly, either portionwise via syringe or dropwise through an addition funnel. Reactions with iodide additive did not benefit from slow addition. The primary side products in both cases are the alkyl dimer and aryl hydrodehalogenated product.
The optimized conditions were then applied to a variety of primary alkyl chlorides and chloroarenes (Scheme 2). Electron-rich aryl chlorides, which were unreactive under our previously published conditions, coupled in 69\u201372% yield (3b, 3f, 3g, 3r). However, a more sterically hindered aryl chloride, 2-chlorotoluene, coupled poorly (3e, 15% yield). While we had coupled electron-poor aryl chlorides with alkyl bromides previously,14 under these conditions electron-poor aryl chlorides could be coupled with alkyl chlorides for the first time, with yields ranging from 53\u201373% yield (3c, 3h, 3i, 3s, 3u, 3v). As expected with PyBCam ligands,20 a variety of heterocycles could be coupled, including both electron-poor quinoline (3s, 63%) and pyridine (3u, 66% and 3v, 73%); and electron-rich indole (3r, 71%) and thiophene (3t, 33%). A particular advantage of cross-electrophile coupling is tolerance for alkyl halides with \u03b2-leaving groups (3z-3ad). The analogous organometallic reagents would be prone to elimination. Finally, secondary alkyl chlorides do couple under these conditions, but in lower yield (3ai, 44%).
Despite the higher temperatures, functional group compatibility remained broad. The low basicity of the conditions allowed us to tolerate both aryl and alkyl pinacol boronic acid esters (3o-3q, 49\u201373% yield), providing opportunities for further elaboration of the products. Acidic N-H (3ag, 60%) and O-H (3ae, 57%) groups are tolerated, which would be a challenge for organomagnesium or organozinc reagents.26 As a testament to the low basicity of the conditions, a free thiol was tolerated (3g, 70% yield), avoiding competing SN2 with the alkyl electrophile and S-arylation (pKa of thiophenol in DMSO is 10.3,27 which makes it more acidic than acetic acid).28 On the other hand, despite the presence of Lewis acids (ZnII salts, Li+ salts) at 60\u201380 \u00b0C, Boc groups on nitrogen were still tolerated (3ag, 60%; 3ah, 71%). While esters were tolerated, we did observe scrambling when two different esters were present due to transesterification (for example, methyl and ethyl ester exchange). For this reason, we coupled chloroarenes bearing esters (3i, 3j) with 1-chlorooctane. Other functional group highlights include a benzylic diethylphosphonate ester (3n, 51%) and a trimethoxysilane (3y, 32%). Despite the low yield, the cross-coupling to form trimethoxysilane product 3y is notable because it is a different approach29,30 to forming functionalized silanes that could be useful in attaching molecules to glass or silica.31 As in our previous studies on cross-electrophile coupling reactions with less reactive substrates, this chemistry can be scaled up using standard techniques (3ac).32
The distinctive feature of this reaction, when compared to other cross-electrophile couplings of aryl halides with alkyl halides, is the ability to engage two relatively unreactive substrates in a selective manner (Scheme 1). There are three keys to the success of this method.
First, LiCl was essential for efficient reduction of the nickel catalyst by the zinc surface. We have recently noted that ZnCl2 can have an inhibitory effect on reduction of nickel catalysts and that lithium chloride is among the best agents for overcoming inhibition,33 consistent with previous reports on reduction of organic molecules.34 Here too, reactions conducted without LiCl resulted in 3% formation of the cross-coupled product and primarily returned both substrates (Supporting Information Figure S2). We also verified that neither organic chloride reacts directly with zinc to form an organozinc reagent (Supporting Information Figure S2).
Second, halide exchange plays a key role by increasing the reactivity of the alkyl chloride. We found that 10\u201330% of bromide or iodide, regardless of how it was introduced, was essential for reasonable reaction rates (Scheme 3 and Supporting Information Figures S4-S7). Importantly, the low concentration of bromide was essential; reactions run without any bromide (Scheme 3d) or with only alkyl bromide (Scheme 3e) provided lower yields than reactions with a catalytic amount of bromide (Scheme 3a \u2013 Scheme 3c and Table 1).
Studies on halide exchange showed that it is fast compared to the rate of reaction (reaching equilibrium in 1\u20132 h vs 24 h for reaction time) and unfavorable (Supporting Information Figure S8-S16). Significantly, the presence of zinc and lithium salts altered the equilibrium to more strongly favor alkyl iodide/bromide. This led to the counterintuitive outcome that increasing total chloride concentration increased alkyl iodide concentration. Under concentrations of salts chosen to mimic those present catalytic reactions, we found that the amount of alkyl iodide increased as the concentration of ZnCl2 increased, although the ratio of alkyl-Cl/alkyl-I remained large in all cases (\u226598:2, Figure S10 and S16). We tentatively attribute this phenomenon to the favorable formation of LiZnCl3 over LiZnCl2Br or LiZnCl2I, resulting in sequestration of chloride as the concentration of Zn2+ increases at later reaction times.35 The halogen exchange is also somewhat faster than reported for exchanges in amide solvents with only sodium bromide, but this process could be catalyzed by zinc: catalysis of alkyl halogen exchange by titanium, zirconium, rhodium, and iron salts has been reported.36
While iodide exchange to enhance the reactivity of alkyl bromides,14 sulfonic acid esters,37 epoxides,38 and chlorides11 in cross-coupling reactions is now well established, the use of bromide is more rare.39 In cases where iodide co-catalysis isn't practical, the use of bromide co-catalysis should be considered.
Finally, studies with a variety of ligands revealed that PyBCam nickel catalysts are unique in being able to react with both substrates at similar rates, even with activation by halide exchange (Table 1 and Supporting Information Figure S1). Compared to nickel complexes of tpy\u2034, which could also react with both substrates but formed both biaryl and bialkyl, nickel PyBCam catalysts avoid biaryl formation entirely and form only small amounts of alkyl dimer. The origin of these differences in reactivity are not yet clear and are the subject of ongoing studies, but it is clear that PyBCam and PyBCamCN are a distinctive, new class of tridentate ligands for nickel catalysis.40
In conclusion, the first selective cross-electrophile coupling reaction of aryl chlorides with primary alkyl chlorides has been developed by the synergistic effect of three changes: a new, selective ligand (PyBCamCN), LiCl to enhance catalyst turnover, and bromide/iodide co-catalysis. The mechanism by which PyBCamCN improves yields is under investigation and will be reported in due course. We expect that the generally unreactive nature of alkyl and aryl chlorides should make this new method to functionalize them a useful addition to synthesis.
", "answer": "Alkyl chlorides and aryl chlorides are among the most abundant and stable carbon electrophiles. Although their coupling with carbon nucleophiles is well developed, the cross-electrophile coupling of aryl chlorides with alkyl chlorides has remained a challenge. We report here the first general approach to this transformation. The key to productive, selective cross-coupling is the use of a small amount of iodide or bromide along with a recently reported ligand, pyridine-2,6-bis(N-cyanocarboxamidine) (PyBCamCN). The scope of the reaction is demonstrated with 35 examples (63%\\xc2\\xb116% ave yield) and we show that the Br\\xe2\\x88\\x92 and I\\xe2\\x88\\x92 additives act as co-catalysts, generating a low, steady-state concentration of more-reactive alkyl bromide/iodide.", "id": 411} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npolycystic ovary syndrome ( pcos ) is the most common endocrine disorder among women of reproductive age , affecting nearly 7% of them .\nthe endocrine hallmarks are hyperandrogenemia and , to a less extent , hypersecretion of luteinizing hormone .\nthe characteristic clinical features of pcos are menstrual irregularity , such as amenorrhea , oligomenorrhea , or other irregular uterine bleeding , and signs of excessive androgen production , such as hirsutism , greasy skin , acne , and obesity .\npcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder , and its morbidity may include hyperinsulinemia , insulin resistance , early onset of type 2 diabetes mellitus , and dyslipidemia .\nobesity is a prominent feature of pcos , occurring in 40 - 50% of pcos patients .\nalso , the prevalence of pcos is increased in overweight and obese women when compared to their lean counterparts .\nthe prevalence rates of pcos in underweight , normal - weight , overweight , and obese women are 8.2 , 9.8 , 9.9 , and 9.0% , respectively .\nprevalence rates reaches 12.4 and 11.5% in women with bmi 35 - 40 kg / m and greater than 40\nobesity worsens the clinical , endocrine and metabolic features of the syndrome , mostly by increasing insulin resistance and hyperinsulinaemia . besides obesity ,\nthe topography of body fat is an important issue . the major endocrine symptom of pcos , hyperandrogenicity , is clearly associated with the amount of fat localized in the upper body sites .\nit is suggested that there is a possible association between diet and risks of pcos .\nthe objective of this study was to characterize the anthropometric and dietary profile of women with pcos and to compare it with that of healthy age - matched women .\nthe study participants , materials , and methods were approved by the student research committee of shiraz university of medical sciences . this study was a case - control study .\nthe study population consisted of patients who attended the clinic for gynecology and obstetrics at motahari clinic ( shiraz medical university ) from april 2009 to august 2009 .\nsixty five women aged between 17 and 48 years , who fit the diagnostic criteria for pcos served as cases .\nthe pcos was diagnosed byultrasound appearance of polycystic ovaries and determination of hormonal parameters based on standard rotterdam criteria 2003 .\nwe excluded patients with any other etiology such as liver , kidney and heart problems .\nthe control group consisted of 65 healthy women who attended the clinic along with their patients and were matched for age with the pcos group .\nall the participants , pcos patients as well as controls , were in good health conditionandwere not on any medication which might affect hormone metabolism or body composition .\nall the participants were non - smokers and none of them was on excessivephysical training .\nfor each participant , a questionnaire of demographic information ( job , exercise habits , education and socio- economic status , etc .\neach participant was asked to provide a detailed history of menstruation and also signs and symptoms of pcos such as acne , hirsutism and greasy skin .\nanthropometric information was gathered as follows : stature ( in cm ) and body weight ( in kg ) were determined for eachparticipant and bmiwas calculated . the waist and hip circumferences were measured and the waist - to - hip ratio ( whr ) was also calculated . to evaluate the dietary intake of the participants , three 24-hour dietary recall questionnaires were filled for each person ( two weekdays and a weekend ) by a trained dietition .\ntotal energy intake ( kcal ) , levels of carbohydrate ( % ) , protein ( % ) , fat ( % ) , sfa ( gr ) , pufa ( % ) and mufa ( % ) intake in the participants were also analyzed , using food processor software nut-4 modified by incorporating the iranian food table .\nstatistical analysis was done using the statistical package for the social sciences , version 13.0 , for windows ( spss , inc . ,\nchicago ) . the independent samplet - test and mann - whitney u test was used to compare the means of the two groups .\nstatistical analysis was done using the statistical package for the social sciences , version 13.0 , for windows ( spss , inc . , chicago ) .\nthe independent samplet - test and mann - whitney u test was used to compare the means of the two groups .\nthe participants of the present study were 65 women with pcos as cases and 65 healthy women as control group .\nthe average age of the participants in the case and control groups was 25.11 6.1 and 26.11 6.5 years , respectively .\nbesides the age variable , the two groups were also matched regarding the education and socio - economic status ( p = 0.499 ) .\nthere was no significant difference in the percentage of women who exercised regularly between the two groups ( 32.3% vs. 35.8% ; p = 0.075 ) .\na significantly higher percentage of pcos women reported pcos in their family than healthy women ( p < 0.001 ) .\nthere was no significant difference between the mean of body mass index of the two groups [ table 1 ] , but the mean of the waist circumference was significantly higher in the pcos group , compared to the control group ( p = 0.016 ) .\nanthropometric characteristics of the participants we also compared the occurrence of three most common signs of this syndrome including acne , hirsutism and greasy skin in the normal weight and overweight subgroups of pcos women [ table 2 ] . although there were no significant differences in greasy skin and acne between the normal weight and overweight pcos patients , a significantly higher percentage of overweight patients had hirsutism compared to the normal weight ( p = 0.009 ) .\npcos signs and dietary pattern in the normal weight and overweight patients with pcos the mean intakes of calorie in the pcos and control group were 1508 581 and 1207 391 kcal , respectively [ table 3 ] .\nthere was a significant difference between the mean calorie intake of the pcos and control groups ( p = 0.001 ) so that the pcos women consumed more calorie than the healthy ones .\nthe mean fat intake ( % ) was significantly higher in the pcos group than the control group ( p = 0.019 ) .\nsfa and pufa were also consumed more in the pcos group ( p = 0.043 and 0.025 , respectively ) .\nas shown in table 2 , no significant difference was seen between their dietary intakes .\npcos is the most common endocrine disorder among women of reproductive age , affecting nearly 7% of them .\npcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder , and its morbidity may include hyperinsulinemia , insulin resistance , early onset of type 2 diabetes mellitus , dyslipidemia , macrovascular disease and thrombosis , endometrial hyperplasia and carcinoma , and obstructive sleep apnea . in the present study , the dietary patterns and anthropometric characteristics of a group of women with pcos and a group of age - matched healthy women were compared .\nthe mean bmi of the two groups was within the normal range ( 19 - 24.9kg / m ) , and there was no significant difference between the two means .\nbut different patterns of fat distribution were seen between the two groups , so that the marker of abdominal obesity , mean of waist circumference was significantly higher in the pcos patients than the healthy controls .\nsimilar results were reached in a study by kirchengast et al . , who showed that lean pcos patients have a significantly higher amount of fat tissue of the total body and the upper body region compared to the lean controls .\nthe gynoid type of fat distribution develops during female puberty and persistsduring the fertile phase of adult life .\nperipheralfat tissue , especially in the lower body region is an importantsource of extra - ovarian estrogen synthesis , because the aromatizationfrom androgens to estrogens takes place there .\nit is important to note that the major endocrine symptom of pcos , hyperandrogenicity , is clearly associated with a preponderance of fat localizedin the upper body sites .\nthis sex specific fat distribution , commonly called android fat distribution , is associated with obesity and a variety of metabolic characteristics , but is also mentioned as an indicator of reduced reproductivecapability of the woman .\ninsulin resistance is independent of the effect of obesity ; both lean and obese women with pcos have evidence of decreased insulin sensitivity , but insulin resistance is most marked where there is an interaction between obesity and the syndrome .\nsystemic hyperinsulinism plays a major role in the development of the hyperandrogenism characteristic of the pcos .\ninsulin also inhibits hepatic synthesis of sex hormone binding globulin , the key circulating protein that binds to testosterone and thus increases the proportion of testosterone that circulates in the unbound , biologically available , or free , state .\na close correlation exists between adiposity and severity of the symptoms in women with pcos , and since acne , hirsutism and greasy skin are the most common variable signs of hyperandrogenism , the prevalence of these symptoms were assessed in two bmi subgroups of our patients : the normal weight and overweight .\nalthough there were no significant differences in greasy skin and acne between the normal weight and overweight pcos patients , a significantly higher percentage of overweight women reported hirsutism compared to the normal weight . in a study by liou et al . , the obese women with pcos did not present with a higher prevalence of hirsutism and in fact they had a lower incidence of acne than non - obese participants . in another cross - sectional study by tamimi et al .\n, hirsutism , the major clinical feature of pcos , did not increase significantly from the normal weight subgroup to overweight and to obese subgroups of pcos patients .\nthere is a fairly general agreement that sex hormone binding globulin ( shbg ) concentrations are much lower in obese women than the lean pcos patients .\nobese women with pcos have high free androgen indices and lower shbg than non - obese women ; therefore , one would expect the obese women with pcos to show more severe functional hyperandrogenism . among hyperandrogenism symptoms ,\nlifestyle modification focusing predominantly on diet and exercise behavior is considered the preferred first - line treatment for pcos management with the primary goal to normalize serum androgens and restore reproductive function .\nthe reported incidence of obesity and insulin resistance among the women with pcos led us to hypothesize that patients with pcos consume foods that contribute to obesity , elevated insulin concentrations , and ultimately , insulin resistance .\nour major findings were that women with pcos had a diet with higher total energy and fat , saturated fat and poly - unsaturated fat compared to the healthy controls .\nbut we did not find any difference between the dietary intakes of normal weight and overweight pcos patients .\nwild et al.21 found that women with pcos had a diet higher in saturated fat and lower in dietary fiber than age - matched control women .\n, investigated the habitual diet and activity patterns of 21 uk women with pcos . in their study ,\nmean percentage energy from fat was 38% ( 12% energy from saturated fat ) , with 68% of women with pcos consuming > 35% energy from fat .\nepidemiological studies suggest an association between a high fat , particularly saturated fat intake and reduced insulin sensitivity . in most of the dietary studies in women with pcos\n, improvements in metabolic and reproductive outcomes have been closely related to improvements in insulin sensitivity , suggesting that dietary modification designed to improve insulin resistance may produce benefits greater than those achieved by energy restriction alone . in an interventional study by thompson et al . on the effects of energy - restricted high protein diet ( 5000 - 6000 kj / d ) , weight loss via energy restriction improved reproductive function , cardiometabolic abnormalities , and hormonal parameters in overweight and obese women with pcos . as reported , in our participants ,\nthis high fat diet might have increased insulin resistance and caused hyperinsulinemia in patients . as we discussed previously , hyperinsulinemia can cause hyperandrogenism . we conclude that in pcos patients , android obesity in a common feature and this abdominal adiposity may be related to pcos complications .\nwe can also report that pcos symptoms are more severe in overweight pcos patients than the normal weight . as to the dietary pattern ,\npcos patients consume more calories and more fat in their diets and this might have been correlated to their disease .\nwe recommend clinical trials to be designed to assess the effects of different patterns of diet and changes in anthropometric indices on the signs and symptoms of pcos .", "answer": "objective : polycystic ovary syndrome ( pcos ) is the most common endocrine disorder among women of reproductive age . \n pcos is considered to be not only a reproductive endocrinopathy , but also a metabolic disorder . \n the objective of the present study was to characterize the anthropometric and dietary profile of women with pcos and to compare it with that of healthy age - matched women.design:in this case - control study , 65 women with pcos served as cases . \n the control group consisted of 65 age - matched healthy women . \n for each participant , demographic , anthropometric and dietary intake data were gathered and compared between the two groups.results:there was no significant difference between the mean of the body mass index of the two groups , but the mean of waist circumference was significantly higher in the pcos group , than the control group ( p = 0.016 ) . compared to the normal weight pcos patients , a significantly higher percentage of overweight patients had hirsutism ( p = 0.009 ) . in dietary analysis , women with pcos consumed more calories and more fat than healthy women ( p = 0.001 and p = 0.019 , respectively).conclusion : it is concluded that in pcos patients , android obesity is a common feature and this abdominal adiposity may be related to the syndrome 's complications . \n pcos symptoms were more severe in overweight patients than the normal weight . \n regarding the dietary pattern , it was indicated that patients with pcos consume more calories and more fat in their diets and this might have been correlated to their disease .", "id": 412} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe program evaluation is generally classified into three types : planning , summative , and formative evaluation .\neven though distinctions between the different types of evaluation are sometimes blurred , differentiating their intent helps us in clarifying our understanding of evaluation process ( 1 ) .\nplanning evaluation takes place before a program begins to give those involved in program development a precise understanding of the program , and it is sometimes referred to as \" pre - formative evaluation \" ( 2 ) .\nsummative evaluation is the typical and most common type of evaluation , which is conducted at the end of a program to provide decision - makers with judgements about the program 's overall merit or worth .\nhowever , although necessary , it often comes too late to be much help ( 3 ) . on the other hand ,\nformative evaluation occurs during the process of a program to provide those who are responsible ongoing information about whether things are going as planned and whether expected progress is being made . if not , this same information can be used to guide necessary improvements , before it is too late ( 4 ) .\neven though there is a great extent of literature on formative evaluation , most of them mainly focus on its conceptual framework , methodology and use .\nsurprisingly , the subsequent effect of using the findings of formative evaluation has not received systematic attention , and few researches demonstrate this by comparing data from the initial program with the final program to show whether there was an improvement in program implementation and impacts ( 5 ) .\nthis study aimed to evaluate the subsequent effect of the formative program evaluation based on a case study of a clinical training program in lao people 's democratic republic ( pdr ) .\nthe main health care delivery system of lao pdr is a government - controlled , public system which has a strong vertical structure with three levels : central , provincial , and district level ( 6 ) .\neven though all health care professionals in the country are required by law to continuously improve their knowledge and skills , the continuing professional development ( cpd ) training system in lao pdr has not yet been functioning well ( 7 ) . in 2012 , under the support of korea international cooperation agency ( koica ) , faculties from seoul national university ( snu ) college of medicine in korea and university of health sciences ( uhs ) in lao pdr launched the \" continuing professional development training project to strengthen the capacity of provincial and district hospitals in lao pdr \" ( 8) . at the beginning of the project , uhs faculties conducted a needs assessment survey in luang prabang province , which was the pilot area for this project .\nbased on the needs assessment results , korean and lao faculties worked together to develop a cpd training program and a handbook including 80 clinical topics on 5 major clinical specialties : internal medicine , surgery , obstetrics and gynecology , pediatrics , and emergency medicine .\nand then , uhs faculties provided a 1-week ' training of trainers ' program for 30 medical faculties of the luang prabang provincial hospital .\nalso , the training management committee composed of provincial hospital executives and department chairs was established to monitor and manage the training effectively .\nfinally , the trained provincial hospital faculties provided a 10-week training program in the provincial hospital for the district hospital health professionals in luang prabang province .\nthe training was conducted 4 times consecutively over 2 yr , and 12 medical professionals , 1 from each district hospital , were invited to each training program . among the total 48 medical professionals , 35 of them were medical assistants , and the other 13 were medical doctors .\nthe training was composed of 5 major clinical sections , and the trainees rotated each clinical section every 2 weeks .\nlecture about clinical topics , observation of trainers ' performance , and trainee 's own medical practice with trainers ' feedback were the main training methods .\nformative program evaluation was conducted during the whole process to continuously improve the training program ( fig .\n1 ) . kirkpatrick model was applied for the program evaluation covering level 1 ( reaction ) and level 3 ( transfer ) ( 9 ) .\nquestionnaire survey and focus group interviews with the trainees were used to evaluate the reaction of the trainees .\nthe questionnaire was designed by the co - work of faculties from snu and uhs based on the literature review ( 1011 ) .\nit was composed of 14 items , regarding the goals and objectives , relevance , organization , trainers ' knowledge , trainers ' communication , trainers ' preparedness , training methods , discussion and interaction , practical session , handbook , facilities , schedule , applicability , and helpfulness of the training program .\nthe trainees were asked to rate the items with a 5-point likert scale ( 1 , strongly disagree ; 2 , disagree ; 3 , neutral ; 4 , agree ; 5 , strongly agree ) ( table 1 ) .\nthe survey was conducted every two weeks at the end of each clinical section of the training program .\nfocus group interview with the trainees was facilitated by the uhs faculties at the end of each 10-week training program .\nthe transfer of the trainees was evaluated through the review of medical records written by the trainees .\ntotal 354 medical records written by 44 trainees before and 3 months after the training program were collected .\nglobal rating with a 5-point anchored scale ( 1 , novice ; 2 , advanced beginner ; 3 , intermediate ; 4 , proficient ; 5 , expert ) was used for the evaluation .\na total of 25 trainers received a half - day workshop before assessing the medical records , and they practiced with some pilot medical records and received feedback during the workshop .\nthe medical records were coded by the coordinator , and they were randomly distributed to the trainers without any personal and time information .\nthe difference of average scores between the medical records written before the training and those written after the training was calculated to evaluate the transfer of the trainees .\nthe evaluation data was collected under the responsibility of the training management committee and analyzed by the study team .\nthe results were shared with the committee and the trainers after the end of each batch of the training program .\nthe committee and the trainers reached a consensus on how to improve the training program through the group discussion based on the evaluation results .\nafter the final end of the training program , the average scores of the survey results and the achievement of global rating scores of medical records among the four batches were analyzed statistically with the anova using spss .\nthe institutional review board of seoul national university college of medicine and seoul national university hospital exempted review of this study since it was an analysis of de - identified data ( irb no .\nthe institutional review board of seoul national university college of medicine and seoul national university hospital exempted review of this study since it was an analysis of de - identified data ( irb no .\naccording to the results of the survey , the trainees were quite satisfied with the training program ( table 2 ) .\nhowever , especially in the early period of the training program , the trainees were not so satisfied in such areas as the organization and schedule of the training program , and discussion , interaction , and practical sessions during the training program . from the second batch ,\nthere was continuous increase of the satisfaction of the trainees in all the items of the questionnaire , and most of the significant improvement happened between the first and the second batch ( supplementary fig .\nthe focus group interviews provided similar but more in - depth view of the trainees ' reactions ( table 3 ) .\nhowever , especially at the first batch of the training , some trainees suggested that there should be more practice and interaction in the training program and the trainers should pay more attention and provide more explanation to the trainees . from the second batch of the training , comments about the program and\nthe trainers became more positive , and there was less criticism about the issues that were previously mentioned . in the second batch , some trainees suggested that the training should be more applicable to the situation of district hospitals , which also seemed to be improved from the third batch of the training program .\nthe average global rating scores of the medical records which were written after the training program were higher than those written before the training , except the second batch ( table 4 ) . and the achievement of the average global rating scores between the medical records before the training and those after the training increased from the first batch to the last batch , especially between the second and the third batch ( supplementary fig .\nthe purpose of this study was to evaluate the effect of the formative program evaluation , which was applied to continuously improve the training program . according to the evaluation results , there was continuous improvement of the reaction and the transfer of the trainees from the first batch to the last batch of the training program .\nwe might have a close look at the ways how the formative program evaluation contributed to the continuous improvement of the training program . at the first batch of the training program ,\nthe trainees were not so satisfied in some areas like organization and schedule of the training program , and discussion , interaction , and practical sessions in the training program .\nsome trainees thought the training activities were not enough for them , and there should be more practical sessions like bed side teaching or real practice rather than lectures .\ntrainees also suggested that the trainer should pay more attention to them and there should be more discussion and interaction between the trainer and the trainees .\nthe review of the medical records written by the first batch trainees showed a minimal achievement of global rating scores .\nthese results of the formative program evaluation were shared with the committee and the trainers at the end of the first batch of the training program .\nthe committee and the trainers reached a consensus on how to improve the training program through the group discussion based on the evaluation results .\nthey decided to increase the training activities , especially practical sessions like bed side teaching and real practice under supervision . and\neven during the lecture time , they agreed to foster more interaction and discussion between the trainers and the trainees .\nthe training management committee also emphasized to the trainers that the trainees are not young students , but experienced medical professionals . at the second batch of the training program ,\nthe average scores of all the items in the survey were much increased , and there was no item which was rated below 4.0 . also the trainee 's comments , especially about the trainers , in the focus group interview became more positive than before .\nhowever , the review of the medical records written by the second batch trainees did not show any achievement of global rating scores .\nafter a group discussion based on the results of the survey and focus interview , the training management committee and the trainers reached on a consensus that there still should be more practical sessions for the trainees , which later could be applicable to the medical practice in the district hospitals . at the third batch of the training program ,\nthe trainees were more satisfied with the practical sessions and more trainees appreciated the applicability of the training program . and\nthe achievement of global rating scores of the medical records was much increased comparing to the first and the second batch .\nthe program evaluation results of the fourth batch showed a minimal improvement of the reaction and transfer of the trainees .\nthere were several key factors which should be noted in this study on the formative program evaluation .\nfirst of all , two levels , level 1 ( reaction ) and level 3 ( transfer ) , of the kirkpatrick model were selected for the program evaluation for the reason that the reaction of the trainees should be closely related to the implementation of the training program and the transfer of the trainees could be a reliable parameter of the outcome or impact of the training program ( 12 ) .\nsecond , the survey for the evaluation of the trainees ' reaction was conducted every two weeks during the training program to improve the reliability of the ratings .\nit was to minimize the dominating effect of the trainee 's emotional experiences of both the peak and the end of the training program ( 13 ) .\nthird , focus group interviews were added to seek more deeply the problems of the training program which were discovered by the survey results . by this\n, the quantitative evaluation using a likert scale and qualitative evaluation using focus group interviews , both of which have their relative merits ( 14 ) , were integrated into the formative program evaluation process . finally , to evaluate the transfer of the trainees , medical records which were written 3 months after the training program were collected , analyzed , and compared with those written before the training .\nit was based on the evidence from the previous studies that most meaningful changes would take place over a longer period of time than just right after the training ( 1516 ) .\nwe were not able to assign a control group and conduct a case - control study due to the small size of the trainees group . and\nthe formative program evaluation did not cover the level 2 ( learning ) and level 4 ( result ) of the kirkpatrick model because of the feasibility and the time limit of the evaluation process .\nfurther study is needed for more delicate study design and concrete results . however , even though it was a pilot clinical training program in lao pdr , the plan for the formative program evaluation was designed from the beginning of the project , and was shared with the all the participants .\nthe whole evaluation process was conducted by the lao health professionals under the guidance and support of the study team . in conclusion\n, the results showed that the formative program evaluation contributed to the continuous improvement of the training program .", "answer": "this study aimed to evaluate the effect of the formative program evaluation on the continuous improvement of a clinical training program for lao health professionals . \n the training program was conducted 4 times consecutively for total 48 health professionals , and the formative program evaluation was carried out during the whole process . to evaluate \n the satisfaction and the transfer of the trainees , the questionnaire survey , the focus group interview , and the trainees ' medical records were used . after the end of each batch of the program , \n the evaluation data were analyzed , and its results were shared with the training management committee and the trainers , who , based on the results , reached a consensus on how to improve the program . \n the evaluation results and the comparison of them among the four batches of the program showed that there was a continuous increase of the satisfaction and the transfer of the trainees , especially in the early period of the program . \n the formative program evaluation which was conducted during the whole process of the clinical training program had a positive effect on the improvement of the program , especially in the early phase , by increasing the satisfaction and transfer of the trainees .", "id": 413} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmanagement of immature root with a necrotic pulp and apical periodontitis is a challenging task .\nobturation of the root canal is difficult because of lack of apical barrier for containing the root filling material .\ntreatment of choice in such cases is the apexification procedure , i.e. , establishing an apical barrier .\nit has also been shown that the use of calcium hydroxide weakens the resistance of the dentin to fracture . in recent times ,\na bonded restoration can be placed without any delay , thus reducing the possibility of root fractures .\nthe major disadvantage of mta is its manipulation due to which its placement in the wide apical area is difficult to achieve .\na matrix can be used in apexification procedures against which mta can be placed and condensed .\nuse of an apical matrix allows for the predictable placement and judicious use of this expensive material .\nseveral materials have been recommended to create a matrix including calcium sulfate , hydroxyapatite , resorbable collagen , and platelet - rich fibrin . in this case series , we are presenting two cases of mta apexification using polyglactin - based resorbable suture material as the apical matrix .\na 16-year - old male patient reported with a chief complaint of discolored maxillary left central incisor .\nhistory revealed that the patient had suffered trauma 8 years back and undergone treatment in a private clinic .\nclinical examination revealed grayish discoloration of tooth 21 and attempted access preparation in the same tooth .\nperiapical radiograph showed well - defined periapical radiolucency and wide open apex in relation to tooth 21 [ figure 1a ] .\nthe final diagnosis was pulpal necrosis with chronic apical periodontitis in relation to tooth 21 .\nafter discussing different treatment options with the patient 's parents , we opted to go for mta apexification with the use of an apical matrix .\nafter rubber dam isolation , the tooth 21 was accessed and working length was established radiographically [ figure 1b ] .\nroot canal was chemo - mechanically debrided with circumferential filing using the international organization for standardization ( iso ) 80 k - file ( dentsply maillefer , switzerland ) in conjunction with copious amount of 0.5% sodium hypochlorite ( shivam industries , india ) .\na volume of 3 ml of 17% ethylenediaminetetraacetic acid ( edta ) solution ( prevest denpro , india ) was used for smear layer removal .\napexcal medicament paste ( ivoclar vivadent ag schaan , liechtenstein ) was placed in the root canal , and access cavity was restored with temp paste ( pyrex exports , india ) .\none week later , tooth was again accessed under rubber dam isolation , and copious amount of normal saline was used to remove any remnants of the calcium hydroxide medicament .\none end of the suture material was modified to form a mesh , whereas the other end is left as such so that it could be used to adjust the position of apical matrix [ figure 1c ] .\nsuture material was saturated with iodine - based radiographic contrast medium iopamidol ( bracco , italy ) for 10 min to render it radio - opaque [ figure 1d ] .\nthe matrix was gently placed on working length with the help of preselected hand pluggers [ figure 1e ] , and its position was verified using radiographs [ figure 1f ] .\nany adjustment required was done using the hand pluggers or free end of the suture material .\nwhite mta angelus ( angelus , londrina , pr , brazil ) was mixed according to manufacturer 's instructions and using hand pluggers , gently condensed against the matrix to form 4 mm of apical plug [ figure 1 g ] . after placing a moist cotton pellet ,\nnext day , root canal was obturated using lateral condensation of gutta - percha ( meta biomed , korea ) and ah - plus root canal sealer ( dentsply detrey gmbh , germany ) , and tooth was restored with brilliant ng bonded resin restoration ( coltene / whaledent , switzerland ) [ figure 1h ] .\nthe patient was recalled after 3 months for clinical and radiographic evaluation . at the follow - up visit ,\nradiograph demonstrated the resorption of the apical matrix and healing periapical lesion [ figure 1i ] .\n( a ) preoperative , ( b ) working length radiograph , ( c - f ) formation and placement of suture matrix , ( g ) mineral trioxide aggregate plug , ( h ) immediate postoperative , and ( i ) 3 month follow - up a 15-year - old female patient presented with the chief complaint of discomfort while chewing in front region of upper jaw .\npatient gave a history of traumatic incident 9 years back for which she had visited a private clinic .\nclinical examination revealed slightly grayish discolored tooth 21 and previously attempted treatment in the same tooth .\nintraoral periapical radiograph showed a well - defined periapical radiolucency surrounding the wide open apex of tooth 21 [ figure 2a ] .\nafter rubber dam isolation , tooth was assessed and working length determined using the radiograph [ figure 2b ] .\nroot canal debridement was done using iso 80 k - file ( dentsply maillefer , switzerland ) and 0.5% sodium hypochlorite ( shivam industries , india ) .\na volume of 3 ml of 17% edta solution ( prevest denpro , india ) was used for smear layer removal .\nroot canal was medicated with apexcal paste ( ivoclar vivadent ag schaan , liechtenstein ) for 1 week .\nafter 1 week , 4 mm of mta plug was formed by condensing white mta angelus ( angelus , londrina , pr , brazil ) against vicryl suture ( johnson and johnson ltd . ,\nnext day , the tooth was obturated using laterally condensed gutta - percha ( meta biomed , korea ) and ah - plus ( dentsply detrey gmbh , germany ) [ figure 2e ] .\nbonded composite resin brilliant ng ( coltene / whaledent , switzerland ) was used for definitive restoration . at the 3-month follow - up visit ,\nperiapical radiograph revealed resorbed apical matrix and healing periapical lesion in relation to tooth 21 [ figure 2f ] .\n( a ) preoperative , ( b ) working length determination , ( c ) suture matrix in place , ( d ) mineral trioxide aggregate plug , ( e ) immediate postoperative , and ( f ) 3 month follow - up\na 16-year - old male patient reported with a chief complaint of discolored maxillary left central incisor .\nhistory revealed that the patient had suffered trauma 8 years back and undergone treatment in a private clinic .\nclinical examination revealed grayish discoloration of tooth 21 and attempted access preparation in the same tooth .\nperiapical radiograph showed well - defined periapical radiolucency and wide open apex in relation to tooth 21 [ figure 1a ] .\nthe final diagnosis was pulpal necrosis with chronic apical periodontitis in relation to tooth 21 .\nafter discussing different treatment options with the patient 's parents , we opted to go for mta apexification with the use of an apical matrix .\nafter rubber dam isolation , the tooth 21 was accessed and working length was established radiographically [ figure 1b ] .\nroot canal was chemo - mechanically debrided with circumferential filing using the international organization for standardization ( iso ) 80 k - file ( dentsply maillefer , switzerland ) in conjunction with copious amount of 0.5% sodium hypochlorite ( shivam industries , india ) .\na volume of 3 ml of 17% ethylenediaminetetraacetic acid ( edta ) solution ( prevest denpro , india ) was used for smear layer removal .\napexcal medicament paste ( ivoclar vivadent ag schaan , liechtenstein ) was placed in the root canal , and access cavity was restored with temp paste ( pyrex exports , india ) .\none week later , tooth was again accessed under rubber dam isolation , and copious amount of normal saline was used to remove any remnants of the calcium hydroxide medicament .\none end of the suture material was modified to form a mesh , whereas the other end is left as such so that it could be used to adjust the position of apical matrix [ figure 1c ] .\nsuture material was saturated with iodine - based radiographic contrast medium iopamidol ( bracco , italy ) for 10 min to render it radio - opaque [ figure 1d ] .\nthe matrix was gently placed on working length with the help of preselected hand pluggers [ figure 1e ] , and its position was verified using radiographs [ figure 1f ] .\nany adjustment required was done using the hand pluggers or free end of the suture material .\nwhite mta angelus ( angelus , londrina , pr , brazil ) was mixed according to manufacturer 's instructions and using hand pluggers , gently condensed against the matrix to form 4 mm of apical plug [ figure 1 g ] . after placing a moist cotton pellet ,\nnext day , root canal was obturated using lateral condensation of gutta - percha ( meta biomed , korea ) and ah - plus root canal sealer ( dentsply detrey gmbh , germany ) , and tooth was restored with brilliant ng bonded resin restoration ( coltene / whaledent , switzerland ) [ figure 1h ] .\nthe patient was recalled after 3 months for clinical and radiographic evaluation . at the follow - up visit ,\nradiograph demonstrated the resorption of the apical matrix and healing periapical lesion [ figure 1i ] .\n( a ) preoperative , ( b ) working length radiograph , ( c - f ) formation and placement of suture matrix , ( g ) mineral trioxide aggregate plug , ( h ) immediate postoperative , and ( i ) 3 month follow - up\na 15-year - old female patient presented with the chief complaint of discomfort while chewing in front region of upper jaw .\npatient gave a history of traumatic incident 9 years back for which she had visited a private clinic .\nclinical examination revealed slightly grayish discolored tooth 21 and previously attempted treatment in the same tooth .\nintraoral periapical radiograph showed a well - defined periapical radiolucency surrounding the wide open apex of tooth 21 [ figure 2a ] .\nafter rubber dam isolation , tooth was assessed and working length determined using the radiograph [ figure 2b ] .\nroot canal debridement was done using iso 80 k - file ( dentsply maillefer , switzerland ) and 0.5% sodium hypochlorite ( shivam industries , india ) .\na volume of 3 ml of 17% edta solution ( prevest denpro , india ) was used for smear layer removal .\nroot canal was medicated with apexcal paste ( ivoclar vivadent ag schaan , liechtenstein ) for 1 week .\nafter 1 week , 4 mm of mta plug was formed by condensing white mta angelus ( angelus , londrina , pr , brazil ) against vicryl suture ( johnson and johnson ltd . ,\nnext day , the tooth was obturated using laterally condensed gutta - percha ( meta biomed , korea ) and ah - plus ( dentsply detrey gmbh , germany ) [ figure 2e ] .\nbonded composite resin brilliant ng ( coltene / whaledent , switzerland ) was used for definitive restoration . at the 3-month follow - up visit ,\nperiapical radiograph revealed resorbed apical matrix and healing periapical lesion in relation to tooth 21 [ figure 2f ] .\n( a ) preoperative , ( b ) working length determination , ( c ) suture matrix in place , ( d ) mineral trioxide aggregate plug , ( e ) immediate postoperative , and ( f ) 3 month follow - up\napexification is defined as a method to induce a calcified barrier in a root with an open apex or the continued apical development of an incomplete root in teeth with necrotic pulp .\nthis chemical has several disadvantages such as difficulty of the patient 's recall management and delay in the treatment .\nfurthermore , there is a risk of tooth fracture after dressing with calcium hydroxide for extended periods . the most promising alternative to calcium hydroxide is mta .\nthe advantages of this material are ( i ) reduction in treatment time , ( ii ) immediate restoration of the tooth , ( iii ) no adverse effect on the mechanical properties of root dentin . in a prospective study ,\nplacement of the material in a wide open area is a challenging task and also there is a risk of extruding this expensive material into periapical tissues .\nlemon advocated the use of a matrix when the diameter of the perforation is larger than 1 mm to prevent the extrusion of sealing material .\nsimilarly , a matrix can be used for the predictable placement of mta in apexification procedures .\nvarious materials have been advocated to be used as a matrix , for example , calcium sulfate , hydroxyapatite , collagen , platelet - rich fibrin .\nthe common limitation shared by these materials is that once placed their position ca n't be adjusted as required .\nvicryl is a synthetic absorbable suture material composed of 90% polyglycolic acid and 10% polylactic acid .\nhowever , the suture material lacks the radio - opacity which makes it difficult to be viewed in the radiographs .\niopamidol was used in our technique to impart radio - opacity to the suture material .\nit is a water soluble nonionic iodine - based contrast medium which is routinely used for angiography , arteriography , contrast - enhanced computed tomography , and urography .\nhowever , a proper history of the patient and sensitivity test should be done before using it . in our technique ,\none end of the suture material was used for the matrix formation , whereas other end was kept outside the tooth so that the placement of the matrix can be adjusted as required .\nafter the matrix was placed at the desired position , the free end of the suture was cutoff and then mta was condensed against it .\nthe apical matrix mentioned here in our study is cost - effective , easily available , and provides for adjustment of its position .\nresorbable suture with a contrast agent may be used as a matrix for mta placement but properly designed clinical trials with long - term follow - up are mandatory to support this novel technique as there is no evidence of such procedure available in the literature presently .\nresearch concentrating on the effect of suture material and contrast media on the healing kinetics can further through some light on this technique .", "answer": "the treatment of choice for necrotic teeth with immature root is apexification , which is induction of apical closure to produce more favorable conditions for conventional root canal filling . the most commonly advocated medicament is calcium hydroxide although recently considerable interest has been expressed in the use of mineral trioxide aggregate ( mta ) . \n mta offers the option of a two - visit apexification procedure so that the fragile tooth can be restored immediately . \n however , difficulty in placing the material in the wide apical area requires the use of an apical matrix . \n materials such as collagen , calcium sulfate , and hydroxyapatite have been used for this purpose . \n this article describes the use of resorbable suture material to form the apical matrix which offers many advantages over the contemporary materials .", "id": 414} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbreast cancer is one of the major causes of mortality in middle - aged women , especially in developed countries . at present , there are no effective ways to prevent breast cancer since its cause remains unknown . therefore , early detection becomes the key to improving the breast cancer prognosis and reducing the mortality rates .\nmammography has been widely recognized as being one of the most effective imaging modalities for early detection of breast cancer .\nhowever , it is a hard work for radiologists to provide both accurate and uniform evaluation for the enormous number of mammograms generated in widespread screening .\na computer - aided detection or diagnosis ( cad ) system , which uses computer technologies to detect the typical signs of breast cancer , has been developed to provide a second opinion for radiologists and to improve the accuracy and stability of diagnosis . in general\n, there are three signs of breast cancer in a mammogram : microcalcification clusters ( mcs ) , architectural distortions , and masses . in this paper\n, we particularly focus on the detection of mcs since they appear in 3050% of mammographic diagnosed cases and show a high correlation with breast cancer .\naccording to the breast image reporting and data system ( bi - rads ) lexicon , mcs are tiny calcium deposits that appear as small bright spots in mammograms . as an example , figure 1 shows an mc in a mediolateral - oblique ( mlo ) mammogram .\nit is often hard for radiologists to find individual mcs in mammograms because they are very small ( typically , 0.051 mm ) in the size and the contrast between the mcs and the surrounding breast tissue is not high enough . \nover the past two decades , there has been extensive research focused on developing the cad tools for automatic detection of mcs in mammograms .\nseveral review papers have also been published on this topic [ 2 , 48 ] .\nas described in , mc detection can be classified into four categories : ( 1 ) image enhancement methods [ 913 ] ; ( 2 ) multiscale decomposition methods [ 1417 ] ; ( 3 ) stochastic modeling methods [ 18 , 19 ] ; and ( 4 ) machine learning methods [ 2028 ] . in , a performance evaluation was summarized using free - response receiver operating characteristic ( froc ) in which a support vector machine ( svm ) approach is found to be superior to conventional methods and is capable of achieving a true positive rate of approximately 90% when the false - positive ( fp ) rate is on average of 1.1 fp clusters per image .\nhowever , such fp is not low enough for clinical application . in this paper\n, we present a new method based on a hybrid method which combines a morphological technique and wavelet decomposition processing for detecting the mcs in mammograms .\ncompared with previous methods , the proposed method can achieve not only a high sensitivity but also a lower fp . in the proposed method , we first use a multistructuring - elements ( ses- ) based top - hat transform to enhance the intensity of microcalcification .\nsubsequently , we employ a wavelet decomposition to refine the enhanced results for removing the false enhanced microcalcifications .\nthen , based on the feature of malignant mcs , threshold processing is used to segment the mcs from mammograms . \nthe rest of paper is organized as follows : section 2 presents a morphological processing technique to enhance the mcs in mammogram . in section 3\nsection 4 presents the detection of the mcs and gives the experimental results by using the proposed method .\nas mentioned in section 1 , the mcs appear as small bright spots in mammograms . in this sense , mcs can be directly segmented by using a threshold process . however , since most mammograms have a low dynamical rang and the intensity contrast between mcs and surrounding tissue is quite low , selection of a threshold for the whole image is not an easy task . as a solution ,\nthe difference of gaussian ( dog- ) based method which approximates the individual microcalcification as a two - dimensional ( 2d ) gaussian kernel has been reported in , but this method only is suitable for detecting the microcalcifications with approximate circle shape . in this section\n, we propose a new method which is based on a morphological filtering technique to enhance the individual microcalcifications for mc detection .\nthe basic idea of the method is to use a set of top - hat transforms based on multi - structuring elements ( ses ) of which sizes and shapes are fitted to the individual microcalcifications to enhance them .\nthe top - hat transform of a gray - scale image f is defined as f minus its opening by structuring element b : \n ( 1)t = f(f b ) , \n where denotes the opening operation ; the difference operation yields an image in which only the components fitting to the se remain . \nfigure 2 illustrates the concept of the top - hat transform in one dimension . \nin the top - hat transform , selection of an appropriate se fitting to the target objects is the key . since\nindividual microcalcifications in mammograms frequently vary both in size and shape , it is imposable to use a single se to remove all of them . to solve this problem\n, we use a multi - ses - based method which uses eight different flat ses , denoted as bi ( i = 1,2 , , 8) to remove the individual microcalcifications in the opening processing . in this paper\n, the ses are a set of lines revolving around its center in a 15 15 array . for a mammogram image with resolution 0.05 mm / pixel\n, the 15 15 array indicates that the objects whose size are larger than 0.75 0.75 mm will be removed in the opening operation . \nfigure 3 shows the flat ses used in the top - hat transform where the dots denote the centers of the ses . for each se bi , i = 1,2 , , 8\n, the opening operation yields an image , denoted by ( f bi ) , in which the individual microcalcifications fitting to the se are removed .\nthen , in order to enhance these individual microcalcifications removed by the opening operation , we use a subtraction between the original image and the maximum of the opening results to obtain an image , given by \n ( 2)e = fargmax(f bi ) . \nfigure 4 shows an original mammogram and an enhanced image obtained from ( 2 ) . comparing figure 4(b ) with figure 4(a )\n, we can see that individual microcalcifications appearing on a complex background were enhanced successfully .\nthese results indicate that the microcalcifications can be easily segmented by using a threshold process .\nhowever , the top - hat transform also enhances some undesired objects in the mammograms , such as mammary glands , vessels , and so on .\ntherefore , a refinement processing is required to remove these undesirable objects from the enhanced mammogram images .\nas mentioned above , although the top - hat transform is capable of enhancing microcalcifications varying in size and shape , a side effect is that the undesirable objects are also enhanced .\nbased on an investigation , we found that these unwanted objects are mainly caused by the soft tissues , such as mammary glands and vessels .\nthe typical feature of them is that they have a relatively higher intensity compared with their surrounding area as well as an inner nonhomogeneous intensity . \nfigure 5 shows a comparison between the microcalcification and the mammary gland after the top - hat transform . comparing figures 5(c ) and 5(g ) , we find that the intensity of microcalcification in the enhanced image approximately equals that of the mammary glands .\nhowever , since the individual microcalcification has almost homogeneous intensity , the size of the enhanced microcalcification is generally larger than that of the mammary gland . figures 5(d ) and 5(e ) show the expanded view of the dashed rectangles in figures 5(c ) and 5(g ) , respectively . we can find that the size of the microcalcification is almost twice as large as the size of the mammary gland .\ntherefore , the enhanced mammary glands can be treated as noise that can be removed according to their size . in this paper\n, we employ a wavelet denoising method to remove the mammary glands because the wavelet decomposition can easily separate them according to their particular size . \nthe wavelet - based procedure for denoising the image consists of the following four steps . \n\na four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .\nsymlet-2 , as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .\nfigures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering . \nfigure 7 shows the decomposition results in which w(4 , m , n ) , w(4 , m , n ) , and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image . \n \na four - scale wavelet transform is used to decompose the image obtained from the top - hat transform .\nsymlet-2 , as the decomposition filters since they have the least asymmetry and highest number of vanishing moments .\nfigures 6(a ) and 6(b ) show the scaling function and wavelet function used in the decomposition filtering . \nfigure 7 shows the decomposition results in which w(4 , m , n ) , w(4 , m , n ) , and w(4 , m , n ) denote the detail coefficients at level 4 size of half the original image . \n\nsince the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .\ntherefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros . \nfigure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero . \n thresholding the approximation and detail coefficients .\nsince the size of the microcalcification is almost twice as large as the size of the mammary gland , the noise caused by the mammary gland can be decomposed in level 4 .\ntherefore , we set the detail coefficients at level 4 as well as the approximation coefficients at level 1 to zeros . \nfigure 7 shows the result of the four - scale wavelet transform in which the shaded coefficients marked are set to zero . \n\nfigures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .\nwe see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold . \n \nfigures 8(a ) and 8(b ) show the results of the inverse wavelet transform of the microcalcification and mammary gland in figures 5(d ) and 5(h ) .\nwe see that the intensity of the mammary gland is clearly reduced so that the microcalcifications and mammary glands can be easily separated using a threshold . \n\n, we use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components . \n \nwe use a thresholding processing to obtain a binary image in which each microcalcification is segmented as connected components .\nin this section , we introduce a procedure that segments the mcs from the mammogram image obtained from the above sections and give some experimental results by using the proposed method .\nas mentioned in section 1 , the mcs are tiny calcium deposits clustering together in the mammogram images . based on an investigation on the bi - rads\n, we found that a typical mc generally has the following two features:(1)an mc usually consists of four or more individual microcalcifications;(2)an mc generally appears within a limited area of size 10 10 mm in mammogram images .\nan mc usually consists of four or more individual microcalcifications ; an mc generally appears within a limited area of size 10 10 mm in mammogram images . \n according to these two features , we use the following two steps to detect the mcs .\nfirst , the binary image is subdivided into blocks that overlap their neighbors both horizontally and vertically .\nthe blocks are of size 200 200 pixels ; for each pair of overlapping blocks , the overlapping boundary region is of size 100 100 pixels .\nsecond , for each block , if the total number of the connected components is larger than three , this block will be labeled as an mc .\nwe developed and tested the proposed method using a database collected by the tohoku university school of medicine .\nthese mammograms are of size 4740 3540 pixels , with a spatial resolution of 0.05 mm / pixel and 16-bit grayscale . \nthe performance of the proposed method is summarized by the true positive rate and false positive cluster per image . \ntable 1 summarizes the experimental results of the proposed method comparing with several previous methods [ 8 , 9 , 13 , 14 , 32 , 33 ] .\nthe proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image . to our best knowledge\n, this performance is better than most state - of - the - art methods in mc detection [ 2 , 34 ] . in the experiments\n, we found that the fps are mainly caused by the linear - structure tissues interlacing with each other or benign calcifications with nonhomogenous intensity . \nsince the characteristics of linear - structure tissues are quite different with that of the mcs , we consider that fps can still be reduced by using a statistic classifier , such as a support vector machine ( svm ) .\nin this paper , we presented a high - accuracy method for the detection of mcs in mammograms .\nthe proposed method combined a multi - ses top - hat transform and a wavelet - based denoising approach to enhance the individual microcalcifications in mammograms .\nexperimental results demonstrated that the proposed method is capable of detecting the mcs in mammograms with high accuracy . in further work\n, we will conduct more experiments on a wider database and improve its performance both in accuracy and computational cost .", "answer": "the presence of microcalcification clusters ( mcs ) in mammogram is a major indicator of breast cancer . \n detection of an mc is one of the key issues for breast cancer control . in this paper \n , we present a highly accurate method based on a morphological image processing and wavelet transform technique to detect the mcs in mammograms . \n the microcalcifications are firstly enhanced by using multistructure elements morphological processing . \n then , the candidates of microcalcifications are refined by a multilevel wavelet reconstruction approach . finally , mcs are detected based on their distributions feature . \n experiments are performed on 138 clinical mammograms . \n the proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image .", "id": 415} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nconventional inguinal hernia repair in children involves ligation of the hernial sac at the internal inguinal ring .\nlaparoscopic surgery has been applied in children , and the repair is based on the same principle .\nthis study aimed to document the authors ' experience with laparoscopic inguinal hernia repair in children .\npatients were admitted in the evening 1 day before surgery and discharged within 24 hours following surgery .\ntwo lateral ports of 3-mm were made through the right and left pararectal region to maintain a triangular orientation . in cases with small defects , laparoscopic ring closure ( lrc )\nwas done with 4 0 absorbable purse - string suture ( figures 1 , 2 , and 3 ) .\nin early cases and when difficulty was noted , saline was injected to separate the peritoneum from cord structures .\nthe procedure was modified in 24% of children with a dilated internal ring ( figure 4 ) .\nligature of the hernial sac at the internal ring is inadequate in such cases . here\nthe sac was identified and dissected from the cord structures and then divided ( figure 5 ) . in patients with a large hernial sac ,\nthe landmarks identified included the iliopubic tract ( ipt ) , arching of fascia transversalis , cord structures , and the peritoneal reflection ( figure 6 ) .\nthe ipt was identified as a shiny white band running under the cord structures at the inferior border of the internal ring .\nthe tranversus arch was identified as the arching of the transversalis fascia immediately above and lateral to the internal ring .\nthe ipt was approximated to the transversus arch by using nonabsorbable 2 0 interrupted suture to narrow the internal ring ( figure 7 ) .\nall patients were evaluated after 5 days , 4 weeks , 6 months , 1 year , and then annually , when possible .\nlaparoscopic ring closure : continuation of the purse string on the inferior aspect of the internal ring .\nlaparoscopic ring closure : completion of the purse string suture and occlusion of the internal ring .\nlaparoscopic iliopubic tract repair : completion of the dissection and landmarks identified : ( a ) dilated internal ring , ( b ) iliopubic tract , ( c ) cord structures , ( d ) transversalis fascial arch .\nninety - three indirect inguinal hernial sacs were closed ( 28 right , 7 left , 58 bilateral ) in 64 children ( 56 boys and 8 girls ) , ranging in age from 3 years to 13 years ( median , 5.1 years ) .\nthe mean operating time for lrc was 25 minutes ( range , unilateral 21 to 35 ; bilateral 28 to 50 ) .\nthe contralateral processus vaginalis was patent in 20% of children . in 24% of children ,\nof the 29 bilateral hernias , 20 underwent lrc , 7 underwent liptr , and 2 underwent lrc on one side and liptr on the other side .\nthe median follow - up was 30 months ( range , 2 to 84 ) .\nthe first recurrence was in a 3-year - old female child after 8 months , following a right lrc .\nthe second one was in a 4-year - old boy after 5 months , following a left lrc .\nthe essential step in the conventional method for inguinal hernia repair in children is simple ligation of the hernial sac without narrowing the open ring . from our point of view\nfirst and the most obvious is the confirmation of the hernia and looking for the contralateral side .\nfirst championed by ger , ring closure is essentially a high ligation of the indirect hernia sac , which is the preferred technique in pediatric patients .\nthis technique re - establishes the usual anatomic relations of the medial aspect of the internal ring and cord structures , giving them a flush union with the transversus abdominis muscle and eliminating the lead point that allows the intestine to enter the inguinal canal .\nligature of the hernial sac at the internal ring alone is inadequate in patients with dilated internal ring ( 24% of children ) , as it does not take care of the component of the dilated ring .\nreports exist in the literature of methods to tighten this dilated ring . in hernias exceeding 4 mm to 5 mm in diameter , the external hemicircumference of the neck was opened to bring the conjoined tendon closer to the crural arch with a nonresorbable suture without the use of a prosthesis .\nipt repair has been described as ringplasty , wherein the deep structures of the lateral iliopubic tract were approximated to the proximal arching musculotendinous fibers of the transversus abdominis muscle gazayerli described a laparoscopic preperitoneal ipt repair by approximating the transversus abdominis to the ipt , similar to the anterior preperitoneal approach described by nyhus and associates .\nwe believe that in children with a dilated internal ring , a routine lrc would be inadequate .\nthis is also observed in our 2 recurrences with one of them occurring within 5 months of lrc .\nthe recurrence rate of inguinal hernias is slightly higher with laparoscopic herniorrhaphy than with the conventional technique .\nfollowing liptr , there have been no recurrences . in children with recurrences after lrc , the surgeon has an undisturbed anatomy for the groin incision ; the risk of an injury to the vas deferens , subsequent testicular atrophy , and the risk of superior displacement of the testicle seem less likely .\nthe problems we faced during liptr were trivial and related to the little scar tissue at the internal ring .\nthis could be explained by some peritoneal fluid passing in between the knots placed during ring closure .\nour series shows that both techniques are safe , reproducible , and technically easy for experienced laparoscopic surgeons .\nthe long - term follow - up of liptr would help assess any technical modifications .\nlaparoscopic inguinal hernia repair in children can be offered , as it is safe , reproducible , and technically easy for experienced laparoscopic surgeons .", "answer": "background : this study aimed to document the authors ' experience with laparoscopic inguinal hernia repair in children.methods:ninety-three hernia repairs were performed in 64 children . \n the neck was closed with a purse string suture by using 4 - 0 absorbable suture.results:ninety-three indirect inguinal hernial sacs were closed in 64 children . \n nine percent of children had an ectopic testis . \n the mean operating time for laparoscopic ring closure was 25 minutes ( range , unilateral 21 to 35 ; bilateral , 28 to 50 ) . \n the contralateral processus vaginalis was patent in 20% of children . in 24% of children , \n the final procedure was modified based on the findings of a dilated internal ring . \n a laparoscopic ilio - pubic tract repair was done in these cases . \n laparoscopic mobilization , orchiopexy followed by ilio - pubic tract repair was done in 9% of children . \n scrotal swelling occurred in one child . \n hydrocoele occurred in one patient . \n recurrence rate was 3.1%.conclusion : laparoscopic inguinal hernia repair in children can be offered , as it is safe , reproducible , and technically easy for experienced laparoscopic surgeons . \n iliopubic tract repair may be added in cases with dilated internal ring . \n recurrence following laparoscopic ring closure can be managed with laparoscopic ilio - pubic tract repair . \n the long - term follow - up of laparoscopic ilio - pubic tract repair is awaited .", "id": 416} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnecrotizing sialometaplasia was first described by abrams et al.1 in 1973 , and since then , other similar cases have been reported .\nnecrotizing sialometaplasia is an inflammatory , ulcerative lesion of the small salivary glands that usually occurs on one side of the hard palate , although it can also occur on the lower lip , posterior molar area , buccal mucosa , the parotid gland , tongue , and in the upper airway23 .\nnecrotizing sialometaplasia occurs more frequently in males , with the ratio of affected males to females approximately 2 to 12 .\nit is histologically similar to mucoepidermoid carcinoma and squamous cell carcinoma but is a benign disease that spontaneously heals within 4 to 10 weeks .\nnecrotizing sialometaplasia of the hard palate re - occurred on the contralateral side after 5 months .\na 36-year - old woman was referred to the gangnam severance hospital ( seoul , korea ) by a private practice endodontist .\nthe patient stated that her palate felt uncomfortable and that her throat had been swollen for a week .\nshe had a history of smoking more than 40 cigarettes a day for 20 years and denied any other medical history .\nendodontic treatment of the upper left first premolar under local anesthesia with 2% lidocaine and 1:100,000 epinephrine was completed by the endodontist before the patient 's arrival to our hospital .\na craterlike ulceration of 3 cm diameter , with necrotic tissue inside , was found on the left hard palate .\na ) the lesion was first diagnosed as either tissue necrosis caused by local injection of lidocaine containing epinephrine or necrotizing sialometaplasia , and was treated palliatively .\nit was not possible to perform a biopsy at that time because the tissue was already necrotized.(fig .\nc ) after 5 months , the patient returned to the hospital for recurrence of the same symptoms on the contralateral side of the hard palate without any particular dental event.(fig .\nb ) microscopically , the palatal lesion showed diffuse necrosis of acini and ducts of palatal salivary glands ; however , the overall lobular structure of the involved gland was preserved .\n3 ) based on histological analyses , the final pathological diagnosis for the palatal mass was necrotizing sialometaplasia . at the 3-year follow - up ,\nthe patient 's oral mucosa of the hard palate was normal , without any signs or symptoms.(fig .\nc ) this study was approved by institutional review board of yonsei university gangnam severance hospital ( irb # 3 - 2015 - 0114 ) , and informed consent was obtained .\nthe cause of necrotizing sialometaplasia is unknown , but it is thought to result from infarctions of the salivary gland tissue125 .\nthe causes of such infarctions may be direct injury , effects of vasoconstrictors , or injuries from needles used in local anesthesia , ill - fitting dentures , drinking , smoking , cocaine use , radiation , infection of the upper airway or allergy , intubation , surgical treatment , and systemic diseases such as sickle cell disease , buerger 's disease , raynaud 's disease , and aids2345 .\nshigematsu et al.6 reported that histopathological changes similar to those associated with necrotizing sialometaplasia may be observed when local anesthesia is repeatedly injected into the hard palate of mice .\nnecrotizing sialometaplasia with ulceration may occur when tissues in the salivary glands are infarcted and the acinar cells are subsequently necrotized .\nbrannon et al.2 reported that the risk of necrotizing sialometaplasia in smokers is about 10% ( 7/69 ) .\nsmoking could cause infarctionsin the salivary gland by continuously stimulating the palate and inducing vascular stenosis . in a previous study ,\nthe researchers were unable to determine the cause of necrotizing sialometaplasia in 44% of the patient sample ( 30/69 ) , and the rate of recurrence was 0% ( 0/14)2 . a number of reports have concluded that the risk of recurrence is normally 0% , and that instances of recurrence on the opposite side are rare .\nhowever , histologically , tissues in the salivary glands show infarction , inflammation , granulation tissue , and squamous metaplasia of the salivary duct .\nbecause such squamous metaplasia is often observed , it may be misdiagnosed as squamous cell carcinoma , and because it is similar to mucoepidermoid carcinoma in that the squamous metaplasia is surrounded by a faint outline of necrotized acinar cells , it is easily misdiagnosed as malignant 1278 . however , despite similarities of infection and necrosis , necrotizing sialometaplasia is distinguished from malignancies because its ductal structure is preserved37 . when necrotizing sialometaplasia is misdiagnosed as a malignancy , irreversible treatment such as radical resection may follow .\nin contrast , some malignancies can be misdiagnosed as necrotizing sialometaplasia and subsequently go untreated .\ntherefore , bascones - martnez et al.5 reported that incisional biopsy is recommended for accurate diagnosis , with periodic treatment until full recovery9 .\nthe stages are not clearly separated and can progress from occurrence to full recovery without any treatment .\nwhen salivary gland tissues become infarcted and are necrotized and separated , the necrotized tissues collapse , creating a crater - shaped ulcer .\nthe surrounding mucous membranes show secondary healing and require approximately 4 to 10 weeks for complete recovery2347 .\npain may or may not be present ; however , if there is pain in the first period of ulcer formation , the use of an analgesic is recommended . because necrotizing sialometaplasia appears as an inflammatory ulcer ,\nsome doctors treat it with antibiotics or steroids , but with no reported effects on clinical symptoms7 .\nour patient case had a negative medical history with the exception of smoking and local anesthesia for dental treatment .\nthus , in the preliminary diagnosis , we diagnosed our patient with necrotized tissue caused by the blockage of the terminal blood vessels from complications of smoking and the use of lidocaine with epinephrine .\nafter 3 weeks of follow - up , the necrotized tissues were no longer present and secondary healing of the soft tissues was apparent .\nfive months after the first occurrence of the lesion , we observed recurrence on the contralateral side of the hard palate without any particular factors other than smoking .\nthe second lesion was still within the initial period of necrotizing when observed , and we therefore conducted an incisional biopsy including both normal and necrotized tissues to confirm the diagnosis of necrotizing sialometaplasia . necrotizing sialometaplasia occurs unilaterally in 71% of previously - reported cases , and on both sides of the median suture line of the hard palate in 12% of cases2 .\nhowever , in our case , there was a second occurrence on the contralateral side with a time lapse between the first and second occurrences , a presentation that is thought to be quite rare .\nour patient was not definitively diagnosed upon the second occurrence , but the second lesion may have been caused by the patient 's heavy smoking habit , because she had experienced no dental events such as the use of local anesthesia .", "answer": "necrotizing sialometaplasia usually heals within 4 to 10 weeks with conservative treatment , and rarely recurs . \n when necrotizing sialometaplasia is present on the hard palate it may occur unilaterally or bilaterally . in this case , necrotizing ulceration occurred on the left hard palate of a 36-year - old woman after root canal treatment of the upper left first premolar under local anesthesia . \n after only saline irrigation the defect of the lesion completely healed and filled with soft tissue . \n after 5 months , however , a similar focal necrosis was found on the contralateral hard palate without any dental treatment having been performed on that side and progressed in similar fashion as the former lesion . \n we conducted an incisional biopsy and obtained a final pathological diagnosis for the palatal mass of necrotizing sialometaplasia . at the 3-year follow - up , \n the patient 's oral mucosa of the hard palate was normal , without any signs and symptoms of the condition . \n we report a case of a second occurrence of necrotizing sialometaplasia on the contralateral side from the first , with a time lapse between the first and second occurrence .", "id": 417} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvenous malformation is defined as malformations comprised of slow - flowing , abnormal dilated veins , and venous network .\nclinically venous malformations ( vm ) are present at birth and tend to grow steadily in proportion to the somatic growth of the child .\nvenous malformations are congenital lesions that affect boys and girls equally with a reported risk of developing other conditions within a specified period of time .\nthe occurrence rate is 1 - 2 per 10,000 births and 0.1 - 1% of a population are found to have this condition .\nhistologic and histochemical studies show that abnormalities are formed by small and large dysplastic post - capillary , thin - walled vascular channels with patchy deficiency of mural smooth muscle .\na 28-year - old male was referred to the oral and maxillofacial clinic for evaluation of multiple swellings on the left side of the face and inside his mouth .\nthe patient first noticed the swelling over the temple when he was 11-years - old . as the boy grew , the swelling also proportionately increased .\nmultiple poorly defined swellings were noted on the left side of the head and neck region around the temple , cheek , and submandibular region [ figure 1a and b ] .\nsimilar lesion was noted in the supraclavicular and scapular region [ figure 2a and b ] .\nthe swelling was pulsatile and increased in size the when patient was standing ( dependent position ) .\nintraorally lobulated swelling was noted on the floor of the mouth in the left sublingual region .\nthe lesion measured 3 4 cm , filling the entire floor of mouth , and purplish discoloration was also noted over the swelling [ figure 3a and b ] .\n( a ) photograph ( front view ) shows swelling over the temple region and ( b ) photograph ( side view ) reveals well defined swelling over temple ( large arrow ) diffused swelling in the cheek , and submandibular region ( small arrow ) .\n( a ) photograph shows a well - defined swelling measuring 1 1 cm in the left supraclavicular region and ( b ) photograph of the scapular region shows a diffused swelling .\n( a ) intraoral photograph shows swelling in the floor of mouth filling the entire floor of mouth ( arrow ) and a small swelling in the buccal mucosa that has a purplish hue ( small arrow ) .\n( b ) intraoral photograph of the labial sulcus reveals a purplish swelling ( arrow ) .\nultrasonography of the submandibular region showed a well - defined hypoechoic lesion having anechoic areas with septations , showing flow inside the lesion .\nultrasonography of the submandibular region with 7 mhz small parts transducer shows heterogeneous hypoechoic lesion with slow flow and hyperechoic foci suggestive of calcifications ( arrow ) . magnetic resonance imaging ( mri)-t2-weighted fat suppression , post - contrast axial images showed hyperintense lesions , which are well - defined with no flow voids .\nall the lesions in the submandibular , cheek , and temple region had similar findings [ figure 5 ] .\ndirect puncture phlebogram of the left frontal scalp region revealed pooling of contrast into cavernous spaces draining into external jugular vein [ figure 6 ] .\n( a ) axial section at the submandibular region shows well - defined hyperintense lesion ( arrow ) in the floor of mouth .\n( b ) axial section at the level of cheek shows well - defined hyperintense lesion in the cheek region ( arrow ) .\nphlebography of the lesion in the temple region shows filling of the entire lesion and draining to the regional area ( arrow ) .\nhistopathological examination revealed several thin - walled venous channels lined by flattened endothelium , supported by a dense uninflamed fibrous connective tissue stroma .\nhematoxylin and eosin stained specimen ( 40 ) shows irregular venous channels ( large arrow ) lined by thin endothelium .\nvenous malformation ( vm ) is the second most common vascular anomaly of the head and neck after hemangioma .\nvenous malformations can occur anywhere in the body but are most frequently seen in the head and neck ( 40% ) , extremities ( 40% ) , and trunk ( 20% ) .\nvms are slow - flow vascular anomalies composed of ectatic venous channels that will continue to grow throughout the patient 's lifetime .\nthey grow slowly in size with age , but their growth may be exacerbated following trauma , sepsis , or hormonal changes and they do not regress spontaneously . both men and women are equally affected .\nvascular malformations are believed to be the result of a congenital error of vascular morphogenesis that occurs between the 4 and 10 weeks of intrauterine life .\nvascular malformations have a quiescent endothelium and are considered to be localized defects of vascular morphogenesis , likely to be caused by dysfunction in pathways regulating embryogenesis and vasculogenesis .\nthese lesions vary in color depending on depth of involvement and range from mild detectable color change to deep purple color .\nthese lesions fill when the patient is standing and are compressible , which helps to distinguish them from lymphatic malformations on physical examination .\nareas frequently involved in the head and neck region are masseter , temporalis , tongue musculature , as well as oral and airway mucosa .\nsoft tissue lesions are most frequently facial in location , with the buccal region being the most common site followed by the mandibular space , sublingual space , tongue , and orbit .\nintraosseous calvarial involvement is most frequent in the frontoparietal region and the mandible is the most frequent location within the facial skeleton .\nthere may , however , be no visible manifestations with deeper lesions . in our case ,\nthe first anatomopathologic classification of vascular lesions based on the microscopic appearance was developed by virchow and wegner .\nmulliken and glowacki ( 1982 ) developed a biological classification of vascular anomalies that included physical findings , clinical behavior , and cellular kinetics and classified them as hemangiomas and vms .\na more recently updated classification of vascular anomalies by international society for the study of vascular anomalies is now widely used [ table 1 ] .\nclassification of vascular anomalies ( issva 2007 ) plain radiographs have limited role in the investigations as they can identify only phleboliths .\nultrasound ( us ) is often the initial investigation to evaluate vascular malformations and it may characterize and define the extent of more superficial lesions . on gray - scale imaging , venous malformations can appear as hypoechoic or heterogenous lesions with anechoic structures visible in 50% of cases .\nin addition , the doppler flow is generally monophasic low velocity flow , and in some cases flow is only discernible with compression and release of the lesion .\nthey typically appear as isointense or hypointense lesions on t1-weighted images , but could be hyperintense depending on the presence of intralesional fat .\nlesions are typically lobulated , which gives them the characteristic bunch of grapes configuration . septations and rounded signal voids corresponding to phleboliths are additional distinguishing features . in t2-weighted or inversion recovery sequences ,\nvms demonstrate high - signal intensity.this imaging modality is used to determine the full extent of the lesion and its relationship to adjacent vital structures .\ngradient echo sequences reveal areas of low signal corresponding to calcification or hemosiderin or thrombosis .\nt1-weighted post contrast imaging demonstrates homogenous or heterogeneous enhancement , and dynamic contrast - enhanced mri has increased the specificity of venous malformation diagnosis .\nvms are best demonstrated by direct phlebography , which fills the sinusoidal spaces and any anomalous veins , allowing assessment of the size and extent of the lesion . in the present study , phleboliths were seen on plain radiography and us features were suggestive of vascular anomaly with slow flow rate . whereas , the mri features were suggestive of venous malformation , which was confirmed by direct phlebography where the lesion was seen draining the regional vein .\nvenous malformations usually are associated with syndromes like proteus syndrome and blue rubber bleb nevus ( bean ) syndrome .\nmultiple treatment options exist for venous malformations , including conservative measures such as head of bed elevation and compression , laser therapy , sclerotherapy , and surgery .\nconservative management of venous malformations is usually reserved for smaller isolated asymptomatic lesions and is also important in controlling the growth and symptoms .\nelevation of the head of the bed is important as it decrease hydrostatic pressure in the malformation , which can lead to expansion and can also decrease symptoms of airway obstruction , swelling , and pain that are experienced .\nsclerotherapy remains a good option for the treatment of venous malformations in the head and neck .\nsclerotherapy involves percutaneous injection of a substance to induce inflammation and thrombosis of the lesion , which then will lead to more long - term fibrosis and hopefully decrease or eliminate the expansion of the lesion .\nsotradecol foam or ethibloc ( glue ) , or the sclerosant is mixed with fibrin glue or ethyl cellulose , bleomycin ( pingyangmycin ) and picibanil ( ok-432 ) have recently been used as sclerosants in asia with promising results .\nlarge cervicofacial venous malformations present a much greater challenge , and one must be prepared to use multimodal therapy to keep the lesion under control .\nthese lesions generally can not be cured as doing so would leave devastating functional and cosmetic results .\ntherefore , therapy is used to control growth , maintain cosmesis , and decrease symptoms .\nvenous malformations are either superficial or deep veins that are abnormally formed and dilated . a thorough examination and investigation of the condition is needed to establish the exact extension of the condition and plan proper treatment .", "answer": "vascular malformations are congenital lesions that are present at birth and do not regress \n . however , they often present later in life . \n they are subdivided into two categories : ( 1 ) slow- or low - flow and ( 2 ) fast- or high - flow malformations . \n low - flow malformations contain combinations of capillary , venous , and lymphatic components . \n venous malformations can occur anywhere in the body , but are most frequently seen in the head and neck ( 40% ) . \n these lesions present in a variety of ways , from a vague blue patch to a soft blue mass , which may be single isolated or may occur in multiple areas . \n treatment depends on the type of lesion , the location , degree of involvement , and the clinical symptoms . \n here we are report the imaging and histopathologic findings in a patient with multiple venous malformations affecting the left side of the face and trunk .", "id": 418} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhowever studies have failed to establish a cause and effect relationship between barium retention in the appendix and subsequent development of the appendicitis .\nit is still not advisable to perform appendectomy in such circumstances without the evidence of an acute episode .\nwe present one such patient who had features suggestive of right ureteric colic and presented with retained barium in the appendix .\na 28 years old male attended our outdoor with an 8 days old x - ray film showing tubular radio - opacity in the right iliac fossa region .\nhe had two episodes of severe pain right lower abdomen in past 2 months for which he underwent barium meal follow through .\nalthough the report came out to be normal but again he had an episode of pain .\nthis time x - ray abdomen was not completely normal and the patient came to our opd for advice .\ndaysevents0barium meal follow through study4x - ray abdomen for repeat episode of pain abdomen12presented to our opd with x - ray filmroutine blood investigations , repeat x - ray abdomen ( fig .\n2 ) done60x - ray abdomen - normal5 monthslost in follow up routine blood investigation were sent and found to be normal .\nrepeat x - ray abdomen confirmed that the findings were not an artifact ( fig .\n1 ) . ultrasound abdomen was advised to rule out abnormalities in right urinary system or some obvious bowel pathology .\na contrast enhanced ct scan of the abdomen was then performed to rule out any bowel pathology especially in the appendix or near ileocaecal region .\nit concluded that the bowel was normal but there was a tiny right renal calculi . an x - ray of abdomen performed 7 days later , showed persistence of the radiographic opacity ( fig .\nwe concluded that this is a case of retained barium in appendix with recurrent right ureteric colic because of passage of renal calculi .\nsymptoms got relieved on conservative therapy and subsequent usg showed no calculi in renal system .\nthe radio - opacity was not noticeable on x - ray abdomen , 2 months after barium study .\nprophylactic appendectomy was not done in our case , and the patient did not developed signs of acute appendicitis till 5 months when he was lost in follow up .\ndaysevents0barium meal follow through study4x - ray abdomen for repeat episode of pain abdomen12presented to our opd with x - ray filmroutine blood investigations , repeat x - ray abdomen ( fig .\nrepeat x - ray abdomen confirmed that the findings were not an artifact ( fig .\nultrasound abdomen was advised to rule out abnormalities in right urinary system or some obvious bowel pathology .\na contrast enhanced ct scan of the abdomen was then performed to rule out any bowel pathology especially in the appendix or near ileocaecal region .\nit concluded that the bowel was normal but there was a tiny right renal calculi .\nan x - ray of abdomen performed 7 days later , showed persistence of the radiographic opacity ( fig .\nbased on above findings and investigation we concluded that this is a case of retained barium in appendix with recurrent right ureteric colic because of passage of renal calculi .\nsymptoms got relieved on conservative therapy and subsequent usg showed no calculi in renal system .\nthe radio - opacity was not noticeable on x - ray abdomen , 2 months after barium study .\nprophylactic appendectomy was not done in our case , and the patient did not developed signs of acute appendicitis till 5 months when he was lost in follow up .\nthe appendix is visualized in 8090% of barium swallow or enema studies , and this is accepted as a reliable sign of a non - diseased appendix but post - examination only 10% of the patients retain barium in the appendix beyond 72 h. its prolonged retention in the appendix has been viewed as altered physiology or pathological .\nalthough barium sulphate is inert and not harmful to the mucosa , cases have been reported where appendicitis developed long after barium studies and were tagged as barium induced appendicitis .\nbaroliths have been conclusively retrieved from appendectomy specimen , even after 3 months following barium study in patients with acute appendicitis . despite these case\nreports studies have failed to prove the cause and effect relationship between barium study and acute appendicitis .\nimportant in this regard is the work of maglinte et al . who studied thirty - one patients with retained barium in the appendix for longer than 72 h and followed them for over 1 year .\nbased on above we conclude that the decision to perform appendectomy should be based on the diagnosis of acute appendicitis and that the prolonged retention of barium in the appendix is not an indication for surgery . in our case since no signs or symptoms were suggestive of acute appendicitis , the active search for other causes were made .\nfinding of small renal calculi in right kidney suggested that the etiology could be ureteric colic .\nif a person presents with retained barium in the appendix , no appendectomy should be performed in absence of findings suggestive of acute appendicitis .\nif atypical presentation is found , then they should be appropriately further investigated . some unusual things like right ureteric colic ( as in our case ) ,\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .\ndr mithilesh kumar sinha : data collections , data analysis and writing , dr rajan kumar sinha : writing .", "answer": "introductionretention of barium in the vermiform appendix for more than 72 h following barium meal study is uncommon \n . it may produce undue concern for increased risk for appendicitis and even prophylactic appendectomies have been performed for this.presentation of casewe encountered one such patient who presented with x - ray plate suggestive of tubular radio - opacity in the right iliac fossa region . \n the patient had episodes of severe pain in the right lower abdomen for which he underwent barium meal study . \n further evaluation and investigations established the diagnosis as , a case of recurrent right ureteric colic with retained barium in the appendix.discussionreview of the literature suggests that , in absence of acute appendicitis there is no role of appendectomy , even in a case of retained barium in the appendix.conclusionif atypical presentation is there , they should be appropriately further investigated .", "id": 419} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nRhodium-catalyzed asymmetric hydrogenation of \u03b2-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position\n\nPaper sections:\n\nHydrogen bonding, an important noncovalent interaction, plays a crucial role in biosystem and enzyme catalysis. Inspired by enzyme catalysis, the strategy of hydrogen bonding has been elaborated and successfully applied in numerous cases of organocatalysis in the past two decades, which provides the synthetic community with many solutions for organic synthesis. 1 Among the successful catalysts, thiourea is a special motif for hydrogen bonding. As a double hydrogen donor, thiourea could activate carbonyl compounds by lowering their LUMO energy. 2 Their effective bonding with neutral functional groups, potent binding affinity, and high tunability make thiourea catalysts versatile for many types of organic reactions. 3 Herein, using ferrocene-thiourea chiral bisphosphine ligands (ZhaoPhos series) and a combination of transition metal catalysis and organocatalysis, we focus on whether two hydrogen bonds from the thiourea group are essential in the transformation of b-cyanocinnamic esters, which are very challenging substrates. When the asymmetric hydrogenation of b-cyanocinnamic esters was carried out, the catalyst (L1) with only one H-bond donor in a precise position performed better than ZhaoPhos (possesses two H-bond donors) in both reactivity and enantioselectivity. This novel discovery provides new insight for the design of catalysts in the areas of organocatalysis and metalorganocatalysis.
Chiral g-aminobutyric acids (GABA) are an essential class of compounds in neuroscience, 4 and many of them are drugs or have potential biological activities in the area of neurotransmitters and brain science, 5 such as Pregabalin, 6 Phenibut 7 and Baclofen 8 (Fig. 1). In addition, many chiral GABA derivatives are common motifs in numerous drugs, such as Rolipram, 9 Brivaracetam, 10 Vernakalant 11 and Enablex 12 (Fig. 1). Thus, the synthesis of chiral GABA and their derivatives has attracted a great deal of interest; however, very limited approaches have been developed. The methods for their synthesis include the following: enzymatic kinetic resolution, 13 biocatalytic asymmetric reduction, 14 asymmetric conjugate reduction with polymethylhydrosiloxane (PMHS) 15 and asymmetric Michael addition. 16 However, asymmetric hydrogenation of b-cyanocinnamic esters, the most straightforward access to synthesize chiral GABA derivatives, has never been reported.
Over the past decades, the transition metal catalyzed asymmetric hydrogenation of functionalized ole\ue103ns has emerged as a powerful and environmentally friendly approach to generate chiral compounds. 17 With the rapid development of catalytic systems, many types of ole\ue103ns bearing functional groups such as carbonyl, 18 sulfonyl, 19 cyano group 20 and nitryl, 21 were hydrogenated in high ee and activities. However, the asymmetric hydrogenation of b-cyanocinnamic esters has not been reported, which is due to two reasons: (1) the electronwithdrawing ester group and nitrile group, which can sharply reduce the electron density of the C]C bond, are disadvantageous for the C]C bond coordination to the metal center, which leads to the low reactivity of these substrates and (2) the linearity of the nitrile group, which is not suitable for assisting the coordination between the C]C bond and metal catalyst, makes it very difficult to achieve high enantioselectivities. 20a,b As a result, it is a very difficult task to achieve satisfactory results from the asymmetric hydrogenation of b-cyanocinnamic esters with the classical bidentate diphosphine/Rh system, as summarized in Table 1.
Methyl (Z)-3-cyano-3-phenylacrylate as a model substrate, a series of bidentate diphosphine ligands including P-chiral diphosphine ligands (entries 1-4), ligands having axial chirality (entries 5-7) and ferrocenyl chiral bisphosphorus ligands (entries 8-10) were tested, which gave low to even trace conversions and almost racemic products. This disclosed that the classical catalyst systems cannot complete this task. Recently, substrate orientation by hydrogen bonds as a strategy in asymmetric hydrogenation has been studied and some progress has been made. 22 Therefore, we tried to utilize the ester group whose carbonyl is a very good H-bond acceptor to improve the reactivity of the electron-de\ue103cient substrate by employing ZhaoPhos-bearing H-bond donors. Although the preliminary result was moderate (entry 11, 28% conversion with 84% ee), it inspired us for further exploration.
In order to obtain the optimal reaction conditions, a serious of solvents were screened (summarized in the ESI \u2020). When the reaction was carried out with 50 atm H 2 gas at 35 C in CF 3 CH 2 OH, full conversion was attained with 95% ee.
To obtain insight into this catalytic system, three other chiral ligands L1-L3 were employed and the results are summarized in Table 2. To our surprise, the N methylation of ZhaoPhos led to an increase in enantioselectivity (entry 2, 98% ee), which is quite different from the previous results we reported. 18f,23 In comparison, when both N-H groups were replaced, almost no conversion was detected (entry 3), which indicated the importance of hydrogen bonds in this reaction. In addition, the ligand L3 without the thiourea group showed very low activity and enantioselectivity (entry 4). These results show that the thiourea motif efficiently activates the carbonyl group through hydrogenbonding interaction and works as an excellent directing agent. Moreover, L1 is superior to ZhaoPhos, which indicates that one hydrogen bond in a precise position is better than two in this asymmetric transformation.
With an optimized set of conditions in hand, we explored the substrate scope and generality of this catalytic reaction. To con\ue103rm the universality of the phenomenon that L1 is superior to ZhaoPhos, almost each substrate was compared (Scheme 1). We thought that enhancement of the steric hindrance of the ester would in\ue104uence this transformation; however, the results indicate that the changes in the substrate have a slight impact on the reaction (2a-2c). Many functional groups, such as methyl (2d), methoxy (2e), phenyl (2f), tri\ue104uoromethyl (2g), and halides (2h, 2i and 2j), at the para position of the phenyl group are compatible with this transformation. Using L1, substrates with meta-or ortho-substitution on the phenyl group are also tolerated and 97% ee and 99% ee values were obtained (2k and 2l, respectively). Generally, poly\ue104uorinated compounds exist in drug molecules, 24 thus a series of poly\ue104uorinated substrates were examined. Substrates with 3,4-di\ue104uoro and 3,5-di\ue104uoro on the phenyl group were tested, and good yields with excellent enantioselectivities were achieved (2m and 2n, respectively). In comparison, when the 3,4,5-tri\ue104uoro compound 1o was employed, the adduct 2o was produced with slightly compromised ee values, which may be due to the electron-poor property of 1o, as discussed above. Other disubstituted substrates could also be accommodated, as exempli\ue103ed by 2p and 2q. Moreover, good yields and excellent enantioselectivities were obtained with substrates containing other aromatic fragments, including naphthalenes and thiophenes (2r and 2s, respectively). To our delight, when the aryl substituent was changed to an alkyl group, such as isobutyl, the product 2t, which can be readily converted to (S)-Pregabalin, was produced with 98% ee. All the results re\ue104ect the fact that L1 bearing a single H-bond donor is more suitable than ZhaoPhos for this reaction. Moreover, when (E)-1a was employed, much lower reactivity and enantioselectivity were obtained, but the con\ue103guration of 2u supports our assumption that the enantioselectivity is inducted by the ester group of the substrates.
To gain a better understanding of the performance of ZhaoPhos and L1, the free energies (kcal mol \u00c01 ) of the hydrogen bonds between different ligands with 2a (DG HB ) were evaluated using the B3LYP-GD3BJ/6-31G** method, 25 as summarized in Table 3. To our surprise, the free energy of the hydrogen bond between 1a and ZhaoPhos is smaller than that between 1a and L1, even at different temperature, which can explain the experimental results very well. These results indicate that one H-bond can perform better than two H-bonds in this reaction, thus we proposed that the stronger hydrogen bond is important in making L1 a more selective catalyst. Both the L1 and Zhao-Phos systems are sensitive to the reaction temperature due to their weaker hydrogen-bonding interaction with substrates at higher temperature.
To verify the accuracy of the catalytic model, the reduction of 1a was performed using L1 of varying ee. As shown in Fig. 2a, a linear correlation between the ee of the ligand and that of the product was observed, which indicates that a 1 : 1 ratio of ligand to metal is present in the catalytic complex. 26 Moreover, a Job plot was drawn and the curve suggests a 1 : 1 binding pattern between L1 and 1a (Fig. 2b), and a 1 : 1 binding pattern between ZhaoPhos and 1a was also suggested (summarized in the ESI \u2020). These experimental data validate our hypothesis, and the catalytic model was illustrated, as shown in Fig. 2c.
In order to further demonstrate the synthetic utility of this methodology, several gram-scale transformations were achieved, as summarized in Scheme 2. First, upon decreasing the catalyst loading to 0.05 mol%, the asymmetric reaction was conducted on a gram scale, and 97% conversion (TON \u00bc 1940) with unchanged enantioselectivity was obtained (Scheme 2a). Then, a high-efficiency synthetic route for (S)-Pregabalin, 13b (R)-Phenibut and (R)-Baclofen 14a was developed. As shown in Scheme 2b, with a 0.1-0.125 mol% catalyst loading, three key intermediates were obtained on a gram scale with high yields (97-98% yield) and excellent ee values (97-98% ee). Thus far, this may be the most concise way to synthesize chiral Pregabalin, Phenibut and Baclofen. Next, gram-scale 2p, which can be readily converted to a chiral d-amino alcohol whose enantiomer can be used in the synthesis of NK1 antagonists directly, 27 was produced (Scheme 2c). Scheme 2d exhibits an efficient approach for the establishment of chiral pyrrolidines. The asymmetric hydrogenation product 2a was reduced by NiCl 2 /NaBH 4 in MeOH and afforded the corresponding lactam 3 in high yield without any loss in enantioselectivity. By treating the lactam with lithium aluminium hydride (LAH) in THF, the chiral pyrrolidine can be readily obtained. 28
\n\nConclusions\nIn conclusion, the \ue103rst asymmetric hydrogenation of b-cyanocinnamic esters has been reported, which provides an efficient approach for the synthesis of chiral GABA derivatives. This transformation exhibits excellent enantioselectivities (up to 99% ee) under mild reaction conditions with low catalyst loadings. Furthermore, this method provides a concise route for the synthesis of (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen, chiral d-amino alcohols, chiral g-lactam and chiral pyrrolidines, which demonstrates the high synthetic utility of the current methodology. Notably, in our ferrocene-thiourea chiral bisphosphine ligand (ZhaoPhos series) system, the catalyst with a single H-bond donor in a precise position performed better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area. This novel discovery provides a new way to design catalysts. Further investigations on the detailed mechanisms of the proposed key hydrogen bonds and the applications of the asymmetric hydrogenation strategy in organic synthesis are in progress in our lab.
\n\nConflicts of interest\nThere are no con\ue104icts to declare.
", "answer": "With the assistance of hydrogen bonds, the first asymmetric hydrogenation of b-cyanocinnamic esters is developed, affording chiral b-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.", "id": 420} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneonatal diabetes mellitus ( ndm ) presenting within the first 6 months of life includes permanent neonatal diabetes mellitus ( pndm ) , which require lifelong therapy , and transient neonatal diabetes mellitus ( tndm ) where the condition shows remission during infancy but relapses in adolescence .\nalmost all cases of neonatal diabetes have monogenic etiology in contrast to the autoimmune diabetes presenting in children beyond 6 months of age .\npndm is associated with defects in pancreatic beta cell development and function . activating mutations in the kcnj11 gene , encoding the subunit kir6.2 , and abcc8 gene ,\nencoding the sulfonylurea receptor 1 ( sur1 ) of atp - sensitive potassium ( katp ) channel , which has a key role in insulin secretion in glucose metabolism , are the most common causes and account for approximately 40% of all cases of pndm12 ) .\nmutations in the glucokinase ( gck ) and insulin ( ins ) genes have also been reported in patients with pndm .\nsulfonylureas close the katp channel by an atp - independent route , leading to increase insulin secretion4 ) .\ntherefore , in many patients with pndm with kir6.2 and sur1 mutations , insulin therapy can be replaced by oral sulfonylureas which offer more improvement in glycemic control and better quality of life35 ) .\nwe report a case of pndm caused by a novel p.h186d heterozygous mutation in the kcnj11 gene whose treatment was successfully transitioned from insulin to oral sulfonylurea .\nher parents were unrelated , and her family was healthy and had no history of diabetes .\nlaboratory results at diagnosis were : blood glucose , 1,041 mg / dl ; ph , 7.025 ; hco3 , 5.1\nmmol / l ; pco2 , 19.8 mmhg ; sodium , 147 mmol / l ; potassium , 5.6 mmol / l ; chloride , 113 mmol / l ; blood urea nitrogen , 31 mg / dl ; creatinine , 1.2 mg / dl ; urine ketone , + + + ; glycosylated hemoglobin ( hba1c ) , 7.7% ; and c - peptide , 0.2 ng / ml . after recovery from diabetic ketoacidosis , she had injections of neutral protamine hagedorn ( nph ) insulin two times a day and regular insulin ( ri ) four times a day .\nher maximal daily insulin dose was at 1.5 u / kg . her insulin requirement was gradually decreased to 0.44 u / kg / day by 4 months of age .\nalthough there were several hypoglycemic events , insulin injection for glucose control after the infancy period could not be stopped .\ngenetic study for neonatal diabetes using genomic dna extracted from peripheral lymphocyte was done at 4.5 years of age , and a novel heterozygous mutation of the kcnj11 gene located on chromosome 11p15.1 and encoding kir6.2 , c.556c > g ( p.his186asp ) , was found ( fig .\ntransition of treatment from insulin to sulfonylurea was attempted at the age of 4.8 . before the trial ,\nlaboratory findings were as follows : hba1c , 6.9% ; fasting glucose , 205 mg / dl ; c - peptide , 0.84 ng / ml ; 24-hour urine c - peptide , 2.2 g ; negative for islet cell antibody ; anti - insulin antibody ; and anti - gad antibody .\nshe was 103.2 cm in height ( 25th-50th percentile ) , 17 kg in weight ( 50th-75th percentile ) and did not have any specific neurological deficit .\noral sulfonylurea ( glibenclamide ) was initiated at a dose of 0.1 mg / kg / day divided into two equal doses .\nthe glibenclamide dose was gradually increased to 0.4 mg / kg / day over 1 week and the insulin was stopped .\noral glucose tolerance test ( glucose , 1.75 g / kg ) was done at 6 months and 1 year after completion of the sulfonylurea transition .\ninsulinogenic index [ insulin ( 30 min-0 min)/glucose ( 30 min-0 min ) ] , a marker of beta cell function , became increased from 0.10 to 0.18 , and acute c - peptide response [ c - peptide ( 30 min-0 min)1,000/glucose ( 30 min-0 min ) ] became increased from 6.48 to 8.29 ( table 1 ) .\nthe patient is now 7.5 years of age with a height of 121.4 cm ( 50th percentile ) and weight of 23.4 kg ( 50th percentile ) .\nblood glucose was well controlled without episodes of hypoglycemia and the hba1c has been lower than during insulin injection ( fig .\nndm is a monogenic form of diabetes that presents within the first 6 months of life .\nheterozygous activating mutations in the kcnj11 and abcc8 gene encoding the subunits kir6.2 and sur1 of katp channel in pancreatic beta cells are the most common and account for nearly half of all cases of pndm12 ) .\nmutations in the glucokinase ( gck ) , insulin ( ins ) genes have also been reported in patients with pndm .\nthe causes of rare syndromic pndm includes recessive mutations in several genes , such as pdx1 , eif2ak3 , gck , ptf1a , foxp3 , neurog3 , neurod1 , rfx6 , ier3ip1 , hnf1b , glis3 , pax6 , slc19a2 , slc2a2 , and wfs167 ) . in tndm\n, imprinted locus at chromosome 6q24 seen in more than half of cases8 ) , and kcnj11 and abcc8 gene mutations are also found in some cases .\nglucose increases intracellular atp level and it induces the closure of katp channels that lead to insulin secretion by pancreatic beta cells . activating mutations in the kcnj11 or abcc8 gene of katp channel lead to katp channels remaining open despite the presence of glucose , thus , insulin secretion can not be increased1 ) . on the contrary , loss of function mutations cause congenital hyperinsulinemia due to the closure of the katp channel and lead to increased insulin secretion\n. sulfonylureas ( su ) can close the katp channel and increase insulin secretion4 ) .\ntreatment response is not expected in patients with mutations in other genes , such as glucokinase gene , foxp3 , and ipf1 .\ntherefore , molecular diagnosis in neonatal diabetes may help identify patients that are likely to respond to oral sulfonylureas .\npearson et al.3 ) reported the responses to sulfonylurea according to mutation types in diabetic patients caused by kcnj11 mutation .\nthere were no differences in blood insulin , c - peptide level , and insulin injection dose between the successful group and unsuccessful group .\nv59 m , r201c , f35v , h46y , r50q , g53r , r201l , e322k , y330s , f333i mutations also belong to the successful group .\nswitching to su was unsuccessful in patients with q52r , i296l , and l164p mutations .\nin addition , failure of switching to su was more related with the presence of neurologic features ( 14% in successful group and 80% in unsuccessful group ) and older age at initiation of su .\nmedian age was 6 years old ( intraquartile range , 3 - 12 years ) in the successful group and 18 years old ( intraquartile range , 6 - 35 years ) in the unsuccessful group3 ) .\nthe report about a mother and daughter carrying the same kcnj11 mutation showed that the daughter could be switched from insulin to su at age 8.5 years , but her mother had an imcomplete response9 ) .\nthe trial of su switching in a poorly controlled diabetic 19 years old patient with r201h mutation , a mutation type expected to respond successfully , failed10 ) .\nthese observations suggest that factors that can affect the success of switching to su include ; mutation type , severity of mutation , and duration of the diabetes .\na long - standing diabetes may lead to islet beta cell exhaustion resulting in nonresponse to su9 ) .\nndm caused by kcnj11 gene mutations is inherited in autosomal dominant pattern , but most of these cases result from new mutations without family history . the patient in this case has a novel mutation ( p.h186d ) in the kcnj11 gene and presented with a mild form of pndm .\nswitching to su with an initial dose 0.4 mg / kg / day was successful at 4.8 years of age .\noral glucose tolerance test in index patient showed improvement in insulin secretion during the treatment at 6 months and 12 months after the use of su .\nalthough she had hypoglycemia every 2 or 3 weeks and experienced a few episodes of hypoglycemia with mental change during insulin treatment , there was no more hypoglycemia after changing to su treatment . oral sulfonylurea therapy is both safe and better than insulin for metabolic control .\nreported side effects of oral su are transitory diarrhea and tooth discoloration in a few patients311 ) .\nmean hba1c was 8.1% in patients with insulin injection and 6.4% in patients with su therapy312 ) .\nchronic su treatment seems to develop no beta cell desensitisation in pndm patients with kcnj11 mutation13 ) .\nearly su therapy at disease onset can permit insulin hypersensitivity and maintained basal insulin secretion , then provide long - term remission in animal subset14 ) . allowing for the potential beneficial effect on neurodevelopmental outcome and glycemic control , empiric tiral of su before genetic testing in neonatal diabetes patients can be considered15 ) . in conclusion , as the mutation type , severity of mutation , and duration of the diabetes are the major factors affecting the success of switching to su , early genetic analysis and trial of sulfonylurea is important in the management of neonatal diabetes .\nfurther studies looking at the result of su treatment and long term follow in pndm patients are needed .", "answer": "permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life . \n it is a rare disorder affecting one in 0.2 - 0.5 million live births . \n mutations in the gene kcnj11 , encoding the subunit kir6.2 , and abcc8 , encoding sur1 of the atp - sensitive potassium ( katp ) channel , are the most common causes of permanent neonatal diabetes mellitus . \n sulfonylureas close the katp channel and increase insulin secretion . kcnj11 and abcc8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits . \n the mutation type , the presence of neurological features , and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy . \n more than 30 mutations in the kcnj11 gene have been identified . here , \n we present our experience with a patient carrying a novel p.h186d heterozygous mutation in the kcnj11 gene who was successfully treated with oral sulfonylurea .", "id": 421} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin vivo , the biologically active form of dna in prokaryotes is negatively supercoiled . the amount of superhelical stress imposed on the dna is determined by the levels of competing dna topoisomerase enzyme activities , and by local events such as protein binding or dna transcription ( 13 ) .\ntransient changes in the level of global dna supercoiling have been observed with several types of environmental stress , including heat shock , cold shock , ph changes , osmotic shifts , transitions from aerobiosis to anaerobiosis and starvation ( 1,2 ) . along with these changes in stress level ,\nthe expression patterns of the bacteria involved were observed to be dramatically altered ( 46 ) .\nreactions occurring on the dna template , including transcription and replication , also affect the local level of supercoiling .\nwhen rna polymerase threads through the dna template , it pushes a wave of positive supercoils ahead , and leaves a trail of negative supercoils behind ( 3,7 ) .\none way in which negative superhelicity can influence regulation is through the destabilizing effect it has on the double helix at susceptible locations within the sequence .\ndestabilization by even a few kilocalories , far less than would be required to open the duplex , can have a profound effect on the ability of a regulatory molecule to unpair the dna , as is required for the initiation of transcription or replication . in this manner\nexperiments have shown that stress - induced duplex destabilization plays essential roles in the transcriptional regulation of several genes ( 810 ) .\nwe have developed computational methods that evaluate the patterns of stress - induced dna duplex destabilization ( sidd ) in dna sequences ( 11,12 ) .\nthese analyses predict the locations where the dna duplex becomes susceptible to separation when under superhelical stress .\nall conformational and thermodynamic parameters are given their experimentally measured values , so there are no free parameters in these analyses . despite this , their results are in quantitative agreement with experiments in all cases where experimental information is available . when the entire escherichia coli genome is analyzed in this way , the sites that are predicted to be easily stress - destabilized are found not to be distributed at random . instead , these sidd sites are highly enriched in those intergenic regions that are known or inferred to contain promoters , and occur infrequently in coding regions ( 13 ) .\nboth components of this pattern have very high statistical significances . the frequency of sidd sites in intergenic regions separating convergent open reading frames ( orfs ) , which are inferred not to contain promoters , are consistent with random .\na similar pattern of sidd sites avoiding coding regions and being enriched in intergenic regions was noted in yeast , although there the strongest sidd sites were in the terminal flanks of genes , not in their promoters ( 14 ) .\nour most recent studies also indicate that those genes in e.coli whose promoters have strong sidd sites are clustered in certain functional groups such as transcription regulators , transport and membrane proteins .\nit is interesting that many known supercoil - responsive genes and environmental stress - responsive genes have highly destabilized sites in their upstream 5 flanks .\nsidd sites have been shown to be important functional elements in regulating transcriptional initiation , transcriptional termination and other biological activities . in e.coli ,\nactivation of both the ilvpg and leuv promoters are mediated by similar mechanisms involving a binding - induced translocation of superhelical tension from a sidd site to the promoter ( 8,9 ) .\nthis translocated superhelical tension facilitates the formation of the open initiation complex by unwinding the dna duplex in the promoter region . in humans ,\nthe initiation of transcription of the c - myc gene is regulated by the binding of fbp to a highly destabilized sidd site ( 15 ) .\nsidd sites also have been implicated in transcriptional termination and chromosomal matrix attachment in yeast ( 16 ) . these and other results show that sidd is an essential component of regulatory mechanisms for a variety of biological activities .\nit is important to understand that sidd properties are not simply reflections of the underlying thermal stability of the sequences involved . stresses couple together the destabilization behaviors of all base pairs that experience them\nthis leads to much more complex , interactive behaviors than that occur with thermal melting .\n[ see figures 1 and 2 of ref ( 17 ) . ] here we describe the database we are compiling of the sidd profiles of microbial genomes .\naccessible over the web at , it gives users an overview of the sidd sites in their selected genome , and their positions relative to the annotated genes .\nthis information will facilitate the identification of regulatory elements , such as promoter - containing regions , in the genomic sequence .\nin addition , the original sidd profiles ( raw data and graphs ) can be visualized and made available for downloading .\nthe refseq sequences of the analyzed microbial genomes were downloaded from the nih microbial website . in all cases\nthe protein gene products are classified into functional categories according to the information in the clusters of orthologous groups ( cog ) database ( 18 ) .\nour research group has developed three algorithmic strategies to evaluate the equilibrium distribution of states of destabilization of a short dna sequence in response to negative superhelicity ( 12,19,20 ) .\nthese methods can calculate the probability of opening of each base pair in the sequence .\none algorithm also calculates the incremental free energy g(x ) needed to guarantee opening of the base pair at position x. this can be done for each base pair in the sequence .\nstrongly destabilized sites require little or no extra free energy to open , so their values of g(x ) are near zero .\nsites that remain virtually as stable as they would be in relaxed conditions ( which is the majority of the genome ) have g(x ) near 10 kcal / mol . partially destabilized sites\nthese methods have been extended recently to enable the analysis of long dna sequences , and successfully applied to the complete genome of e.coli ( 13,17 ) .\n( for detailed information on the algorithms and the methods for analyzing their results , please refer to the cited publications . )\nthe sidd analysis of complete microbial genomes has been semi - automated on a 38 node apple cluster .\nall sidd profiles were calculated at superhelical density = lk / lk0 = 0.06 , a moderate physiological value .\nthe results from the calculations were manually reviewed for integrity , then their global characteristics were analyzed by a set of perl scripts and c++ programs .\nthe results were directly channeled to a postgres database for storage , visualization and further analysis .\nas of the present ( september 8 , 2005 ) there are 134 analyzed microbial genomes in this database , 118 from bacteria and 16 from archaea .\nwe update the database whenever the sidd analysis of another fully sequenced genome is completed , so the number of analyzed genomes will rise in the future . for each analyzed genome\neach sidd site in the graph is a set of contiguous base pairs for all of which g(x ) < 8 kcal / mol .\nthese sidd sites were binned into disjoint sets according to the minimum value gm that g(x ) attains within them .\nthe lowest bin is determined by gm 0 , and the other bins contain the sidd sites satisfying i1 <\ngm i for i = 1 , , 6 . a color map scheme is used to represent these binned sidd sites .\nthe sidd sites in all the fully analyzed bacterial genomes have a similar pattern of distribution to that reported previously for the e.coli genome ( 13 ) .\nstrong destabilization preferentially occurs in the intergenic regions separating divergently ( div ) or tandemly ( tan ) transcribed orfs , while avoiding coding regions .\ndestabilization in intergenic regions separating convergently transcribing orfs ( con ) , which may be inferred not to contain promoters , is consistent with random .\nthis trend is clearly demonstrated in figure 2 , which summarizes data from the analysis of sidd locations in 42 bacterial genomes . for each genome in the siddbase database\nwe provide a table summarizing the number of sidd sites at each level of destabilization , and the number of these that occur in the three types of intergenic regions div , tan and con .\nsystematic analysis is underway to compare the sidd properties of different strains of the same species , between different phylogenetic groups of the same kingdom and between different kingdoms .\none also can display detailed sidd information for any specific region of interest , as shown in figure 3 .\nthese requests can be made by clicking on a region of the circular map , or by specifying the site either by identifying an annotated gene it contains or by its chromosomal location .\nthe figure displayed is a plot of the oriented genes in a 10 kb window centered on the requested position , together with the locations of the sidd sites in the region .\nthe genes are labeled , their orientations are shown by arrowheads , and they are color coded according to their cog classification .\nx. ) the end of an arrowhead corresponds to the stop codon position of a gene .\nthe sidd sites are shown as colored bars , coded according to their gm values , and displayed below the line showing the annotated genes .\nthe graph of the sidd profile of a 5 kb long region centered on a sidd site can be viewed by clicking on the color bar corresponding to that site .\nwhile the sidd calculation for an entire bacterial genome is time consuming , calculations for short dna sequences ( viz 5 kb ) can be executed efficiently . we have provided a website where users can calculate sidd profiles of short sequences of interest to them .\nthere one can set some of the calculation parameters , including the assumed superhelix density .\nit should be noted that the results calculated from the web server may not necessarily be identical as the ones displayed on this database , even when the sequences and the parameters are the same .\nthe sidd profile of a dna segment in this database was calculated in its native global genomic context , while the results from the web server calculation were not .\nthe current database only contains sidd profiles of complete genomes from prokaryotes and archaea . in the future we also will deposit the results of sidd analyses for eukaryotic genomes .\ninitially this will be yeast , at least one complete chromosome from each fully sequenced eukaryote , and the encode regions of the human genome .\nwe intend eventually to include the sidd profiles of the complete genomes of all fully sequenced model organisms\n. we will also provide sidd profiles of specific prokaryotic genomes at several superhelical densities .\nwe will add further functionalities to the database as these are developed , including sidd - based ( or sidd - assisted ) promoter predictions .\nwe will continue to analyze more microbial genomes as their sequences are completed , and we will periodically update our analyses in response to significant changes in ncbi refseq sequences .\nthe genes are plotted in the inner circle , color coded according to their cog classifications as shown in the gene color map .\nthe sidd sites are shown in the outer circle , color coded according to their minimum sidd energy as shown in the sidd color map .\nthe ratio of the observed number of sidd sites to the number expected if they were located at random . this ratio has been calculated for sidd sites that overlap intergenic regions whose flanking orfs are in any of three orientations ( div , divergent ; con , convergent ; and tan , tandem ) , and also for those that occur within coding regions .\nthese results were calculated from the sidd profiles of 42 bacterial genomes that were chosen to represent the phylogenetic diversity of sequenced genomes and the range of at / gc ratios .\nthe x - axis is the sidd level ; the y - axis is the ratio of predicted sidd sites found in the regions to the expected number of such sites if they were located at random .\nthis shows that the pattern reported previously in e.coli k12 occurs throughout the sequenced prokaryotes .\nthis view is obtained from the window of figure 1 by clicking on a gene , or by entering a gene name or chromosomal location into the appropriate field .\nthe genes are annotated , and the sidd sites are displayed as colored bars belowthe line .\nclicking on a sidd color bar gives an annotated sidd profile centered on that region , as shown .", "answer": "prokaryotic genomic dna is generally negatively supercoiled in vivo . \n many regulatory processes , including the initiation of transcription , are known to depend on the superhelical state of the dna substrate . \n the stresses induced within dna by negative superhelicity can destabilize the dna duplex at specific sites . \n various experiments have either shown or suggested that stress - induced dna duplex destabilization ( sidd ) is involved in specific regulatory mechanisms governing a variety of biological processes . \n we have developed methods to evaluate the sidd properties of dna sequences , including complete chromosomes . \n this analysis predicts the locations where the duplex becomes destabilized under superhelical stress . \n previous studies have shown that the sidd - susceptible sites predicted in this way occur at rates much higher than expected at random in transcriptional regulatory regions , and much lower than expected in coding regions . \n analysis of the sidd profiles of 42 bacterial genomes chosen for their diversity confirms this pattern . \n predictions of sidd sites have been used to identify potential genomic regulatory regions , and suggest both possible regulatory mechanisms involving stress - induced destabilization and experimental tests of these mechanisms . \n here we describe the siddbase database which enables users to retrieve and visualize the results of sidd analyses of completely sequenced prokaryotic and archaeal genomes , together with their annotations . \n siddbase is available at .", "id": 422} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\namblyopia is the leading cause of decreased vision among children , with refractive errors as the most important cause of this condition . because of the importance of early diagnosis and treatment of amblyopia ,\nhowever , this method is limited because it requires an experienced examiner and an excessive amount of time . to overcome these limitations ,\nseveral photorefractors were developed . among these was the plusoptix s09 photorefractor ( plusoptix gmbh , nuernberg , germany ) , developed for children and the disabled , and is a noninvasive tool for the rapid assessment of both eyes for refractive errors , pupil size , and inter - pupillary distance .\nin total 77 eyes in 40 children aged 2 to 10 years were evaluated in uijeongbu st .\nthis study was conducted according to the guidelines of the association for research in vision and ophthalmology and the 1975 declaration of helsinki .\nchildren were excluded when they had eccentric fixation , optical media opacity , or exceeded the plusoptix s09 manufacturer 's recommendations of a refractive error of a maximum spherical range of 7.00 to + 5.00 d and a pupil size range of 3 to 8 mm .\nthe patients were categorized according to 2 methods : ( i ) 11 eyes with hyperopia +3.0 d and 66 eyes with hyperopia < + 3.0 d , emmetropia , and myopia ; ( ii ) 12 eyes with cycloplegic and noncycloplegic refraction of spherical power +2.0 d and 65 eyes with cyclopegic and noncycloplegic refraction of spherical power\n< + 2.0 d. all refractive errors ( spherical power , cylinder power , and spherical equivalent ) were determined in the following order : ( 1 ) photorefraction without cycloplegia using the plusoptix s09 ; ( 2 ) autorefraction without cycloplegia ( noncycloplegic ) using the cannon autorefractometer ( rk - f1 , canon , tokyo , japan ) ; ( 3 ) cycloplegic autorefractometer using 1% cyclopentolate ( 1% cyclogyl ) .\nall cycloplegic autorefractomery was performed within 30 minutes of the use of 1% cyclopentolate 3 times per 5 minutes .\ncomparisons between the measurements were performed using paired t - tests and pearson 's correlation analysis .\nall statistical analyses were performed using the spss statistical package 19 ( spss for windows , chicago , il ) . a value of p < 0.05 was taken to indicate statistical significance .\nthere was no statistical difference between the 11 eyes with hyperopia of +3.0 d and the 66 eyes with hyperopia of < + 3.0 d , emmetropia and myopia for age and sex .\nin addition , there was no statistical difference between the 12 eyes with cycloplegic and noncycloplegic refraction of spherical power +2.0 d and the 65 eyes with cyclopegic and noncycloplegic refraction of spherical power < + 2.0 d ( table 1 ) .\nthere was no difference between the plusoptix s09 and cycloplegic autorefractometer for both spherical power and equivalent in all of the children .\nin contrast , there was a statistical difference between the plusoptix s09 and noncycloplegic autorefractometer ( p < 0.001 ) ( table 2 ) .\npearson 's correlations between the plusoptix s09 and cycloplegic autorefractometer for spherical power , cylinder power , and spherical equivalent were 0.748 , 0.893 , and 0.782 , respectively , whereas between the plusoptix s09 and noncycloplegic autorefractometer these were 0.559 , 0.870 , and 0.580 , respectively .\nthese results indicate that the spherical power and spherical equivalent determined using the plusoptix s09 correlated more closely with those determined using the cycloplegic autorefractometer than using the noncycloplegic autorefractometer ( table 3 ) .\nalthough there was no statistical difference between the plusoptix s09 and cycloplegic autorefractometer in the spherical power and spherical equivalent in all of the patients ( table 2 ) , the mean spherical power and equivalent recorded using the plusoptix s09 was 2.91 0.90 d and 2.22 0.93 d , respectively , whereas these recorded using the cycloplegic autorefractometer were 4.66 0.93 d and 4.25 0.80 d in hyperopia of +3.0 d , respectively .\nthere was a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical power and spherical equivalent in hyperopia of +3.0 d ( paired t - test , p < 0.05 ) .\nin addition , in patients of cycloplegic and noncycloplegic refraction of spherical power +2.0 d , there was a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical equivalent ( paired t - test , p = 0.015 ) ( table 4 ) .\nthere was significant difference between the plusoptix s09 and cycloplegic autorefractometer according to the scatter plot for spherical power and equivalent in hyperopia of +3.0 d ( fig .\ncpr = cycloplegic refraction , se = spherical equivalent , sp = spherical power .\namblyopia is the leading cause of decreased vision among children and affects 2% to 5% of the population .\nearly diagnosis and treatment may lead to better visual outcomes and decrease the severity and prevalence of amblyopia . because of the importance of early diagnosis , several screening methods for amblyopia are used .\nhowever , this method is limited because it requires an experienced examiner , is time consuming , and in general needs sedation of children <3 years old with limited co - operation . in contrast\n, the photo refractor is easy to use in examining younger children without the need for cycloplegic drops or sedation .\nalthough an ideal screening test would have 100% specificity , 100% sensitivity , and 100% positive predictive value , there is no screening method with this level of accuracy .\nmany studies have shown the plusoptix to be a rapid , accurate , and noninvasive refractometer in preschool children and in individuals with intellectual or physical disabilities , and it has excellent specificity and sensitivity .\nthe mean spherical power and spherical equivalent recorded using the plusoptix s09 were 1.53 2.01 d and 1.33 1.97 d , respectively , whereas using the cycloplegic autorefractometer they were 0.61 2.02 d and 0.73 2.05 d , respectively , in all the children , which were not significantly different between the 2 devices ( paired t - test , p > 0.05 ) .\nwe observed significant pearson 's correlation coefficients of 0.748 , 0.893 , and 0.782 between the plusoptix s09 and cycloplegic autorefractometer for spherical , cylindrical , and spherical equivalent refractive errors , respectively .\nthese values are similar to those of 0.76 , 0.86 , and 0.76 , respectively , reported by rajavi et al .\nin contrast , the mean spherical power and spherical equivalent were significantly different using the plusoptix s09 ( 2.91 0.90 d and 2.22 0.93 d , respectively ) and the cycloplegic autorefractometer ( 4.66 0.93 d and 4.25 0.80 d , respectively ) in hyperopia of +3.0 d , ( paired t - test , p < 0.05 ) . because accommodative capacity leads to a myopic shift in over - moderate hyperopia , a statistical difference between the plusoptix s09 and cycloplegic autorefractometer for the spherical power and equivalent was expected .\nthis shift was reported to be 3.0 d and 1.9 d in some children by erdurmus et al and dahlmann - noor et al , respectively .\nschaeffel et al demonstrated a myopic shift of 2.4 d in children wearing + 3.0 d glasses with noncycloplegic photorefraction . in conclusion\n, the plusoptix s09 can provide a rapid and easy method of refraction for amblyopia screening in young children and detecting risk factors for refractive amblyopia .\nhowever , when it is used to estimate the refractive error in a child with hyperopia of +3.0 d , the refractive error should be corrected after a comparison of the refractive errors of the plusoptix s09 with those of a cycloplegic autorefractometer .", "answer": "abstractthe aim of the study is to compare outcome measures of refractive error obtained using the plusoptix s09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics in children.we reviewed the medical records of 40 patients ( 77 eyes ) who were classified using 2 methods . \n the patients were first assigned to 2 groups consisting of 11 eyes with +3.0 d and 66 eyes with < + 3.0 d , and then to 2 groups of 12 and 65 eyes with cycloplegic and noncycloplegic refraction of spherical powers +2.0 d and < + 2.0 d , respectively . \n we compared the outcome measures of refractive error using the plusoptix s09 photorefractor and an autorefractometer of noncycloplegics and cycloplegics.there was no statistically significant difference between the plusoptix s09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent . \n in contrast , there was a statistically significant difference between the plusoptix s09 photorefractor and noncycloplegic autorefractometer ( p < 0.001 ) . \n there was a statistically significant difference between the spherical equivalent of the plusoptix s09 photorefractor and cycloplegic autorefractometer in children with hyperopia +3.0d and with cycloplegic and noncycloplegic refraction of spherical power +2.0 d. we also found a significant difference between the outcomes of the plusoptix s09 photorefractor and cycloplegic autorefractometer in the spherical power and spherical equivalent for children with hyperopia +3.0 d.the refractive error of the plusoptix s09 photorefractor was similar to that of the cycloplegic autorefractometer , in contrast to the noncycloplegic autorefractometer . \n however , the plusoptix s09 photorefractor is an inaccurate tool to estimate the refractive errors of children with moderate hyperopia .", "id": 423} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 52-year - old woman with granulocytic sarcoma affecting the anterior cranial fossa and frontal sinus was commenced on ade ( cytarabine , daunorubicin and etoposide ) and mylotarg ( gemtuzumab ) through a peripherally inserted central catheter ( picc ) line as part of the aml 17 trial ( http://aml17.cardiff.ac.uk/aml17/default.aspx ) .\nshe was known to have a beta - lactam allergy manifest as an erythematous rash . on day 9 of chemotherapy ,\nher fever resolved after 48 hours and meropenem was stopped after 7 days . on day 18 of chemotherapy\nshe remained febrile over the next three days and caspofungin was started in view of high - resolution computed topography ( hrct ) chest findings compatible with possible fungal infection and a positive initial serum galactomannan assay ( although the repeat specimen was negative ) .\nmeropenem was therefore replaced with ciprofloxacin as it was thought to be responsible for the rash .\nall cultures including multiple blood cultures and picc line site swabs were culture negative . on day 31 of chemotherapy she was still febrile and blood cultures from peripheral veins and the picc line taken on day 30 yielded gram - positive cocci in pairs and chains after 24 and 11 hours ' culture respectively .\nthe isolate was identified as leuconostoc lactis using the bd phoenix identification ( becton , dickinson and company , usa ) and api rapid i d 32 strep systems ( biomrieux , france ) .\nmean inhibitory concentrations ( mics ) determined by e - test ( ab biodisk , sweden ) were : penicillin 0.5 mg / l , vancomycin > 256 mg / l , teicoplanin 256 mg / l , ciprofloxacin 1.0 mg / l , tigecycline 0.064 mg / l , linezolid 1.5 mg / l and daptomycin 0.064 mg / l . on day 32 of chemotherapy , ciprofloxacin and teicoplanin\nthe next day therapy was changed to tigecycline ( 50 mg iv q12h ) because of concerns over myelotoxicity ( anaemia and thrombocytopenia ) associated with linezolid .\ndaptomycin was unavailable in the hospital formulary and ampicillin was not used due to concerns over beta - lactam allergy and a borderline penicillin e - test mic .\nthe patient continued to have low - grade fevers over the next four days , despite a negative transthoracic echocardiogram . on the fourth day of treatment , however , her fever resolved and she was discharged from hospital after completing 8 days of tigecycline , to which she had no adverse effects .\nleuconostoc spp . are catalase - negative , gram - positive , facultatively anaerobic coccobacilli .\nthey are environmental organisms often found on plants , dairy products , vegetables , wine and occasionally in human vaginal and stool samples . although an uncommon human pathogen , cases of bacteremia , endocarditis , pneumonia , meningitis , osteomyelitis , peritonitis , brain and liver abscesses have been described .\nand other gram - positive antimicrobial - resistant organisms are increasingly recognised as important pathogens in neutropenic patients probably due , in addition to immunosuppression , to the use of indwelling intravascular devices , antibiotic prophylaxis and evolution of chemotherapeutic agents .\ninfection with leuconostoc may cause fever , intravenous catheter - related sepsis , bacteremia , abdominal pain , gastroenteritis , colitis or meningitis in this group of patients . other reported risk factors for infection\nremoval of intravenous catheters alone has been shown to be curative in some patients without the need for antimicrobial therapy .\nare intrinsically resistant to glycopeptides , owing to the production of peptidoglycan precursors ending in d - ala - d - lac , but are usually susceptible to penicillin , ampicillin , aminoglycosides , clindamycin , minocycline and macrolides .\nin addition , linezolid and daptomycin have been used successfully to treat leuconostoc bacteremia , although linezolid mics of leuconostoc spp .\nalthough the organism has been shown to be resistant to cefoxitin , it is susceptible to cefotaxime in vitro .\ntigecycline , a glycylcycline , is a broad spectrum synthetic derivative of minocycline which has a broad spectrum of activity against various gram - positive and gram - negative bacteria including multidrug - resistant strains , anaerobic bacteria and atypical organisms .\nit has proven to be useful in the treatment of hospital - acquired infections caused by vancomycin - intermediate and vancomycin - resistant enterococci ( vre ) , meticillin - resistant staphylococcus aureus ( mrsa ) , extended - spectrum -lactamase ( esbl)-producing enterobacteriaceae , multidrug - resistant acinetobacter baumanii and penicillin - resistant streptococcus pneumoniae . in the uk ,\nits licensed indications are complicated intra - abdominal and complicated skin and soft tissue infection .\nit is also licensed for the treatment of community - acquired pneumonia in the us .\nalthough tigecycline has been demonstrated to be a safe and effective second - line option in microbiologically documented infections in neutropenic patients , there have been no trials to determine whether tigecycline is effective in neutropenic bacteremia and there are also theoretical concerns surrounding low serum concentrations ( due to a large volume of distribution ) and its mostly bacteriostatic activity .\nit is for this reason that tigecycline is not generally recommended for primary bacteremia but it is used for secondary bacteremia associated with complicated skin and soft tissue infections , intra - abdominal infections and community - acquired pneumonia . despite these concerns , here\nwe report the first successful use of tigecycline in the treatment of leuconostoc bacteremia in a neutropenic patient .", "answer": "leuconostoc lactis is a recognised cause of infection in immunocompromised hosts . \n it is intrinsically resistant to multiple antibiotics and treatment options may be limited . \n we report a case of safe and effective use of tigecycline in the treatment of leuconostoc catheter - related line sepsis in a neutropenic patient . to our knowledge \n , this is the first reported case of successful use of tigecycline for leuconostoc bacteremia .", "id": 424} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients with diabetes are at increased risk of morbidity and mortality from cardiovascular disease ( cvd ) compared to normoglycemic controls.1 several additional factors may be associated with this increased risk , including persistent hyperglycemia , untreated hypertension , and dyslipidemia characterized by raised serum triglycerides ( tg ) and low concentrations of high - density lipoprotein cholesterol ( hdl - c).2 the reduction in cardiovascular events produced by statins in patients with diabetes is broadly consistent with that in normoglycemic , dyslipidemic controls . in the collaborative\natorvastatin diabetes study ( cards ) , a primary prevention study in type 2 diabetes mellitus ( t2 dm ) , atorvastatin reduced coronary heart disease events by 36% , stroke by 48% , and mortality by 27%.3 in a meta - analysis of secondary prevention studies in t2 dm , statins reduced cardiovascular events by 28% and strokes by 32%.4 despite this efficacy , a considerable residual cardiovascular risk remains among patients receiving statin therapy.2,5 hypertriglyceridemia ( > 1.7 mmol / l ) alters the composition of atherogenic particles and may make an important pathophysiological contribution to the residual cardiovascular risk.6 indeed , the current european atherosclerosis society consensus statement recommends treating hypertriglyceridemia of 1.7 mmol / l.6 statins , as well as lowering ldl - c , reduce blood triglyceride concentrations by up to 40%.7,8 only a few previous studies have evaluated hypertriglyceridemia in statin - treated patients with t2dm.9,10 however , there is little data evaluating these patients in primary care in the uk .\ntherefore , this audit assessed the prevalence of residual hyperlipidemia and the potential need for additional lipid - lowering therapy in individuals with t2 dm treated with statins in primary care in the uk .\nthis cross - sectional , observational study audited all patients with diabetes from the first 40 primary care practices that agreed to participate from an existing panel established by an independent clinical research organization ( quintiles commercial uk limited , bracknell , uk ) .\nprescriptions issued were assessed during the preceding 4 months and repeat prescriptions were included . after excluding patients with forms of diabetes other than t2 dm , the patients were stratified according to the european society of cardiology ( esc ) \nfeasible treatment targets in patients with diabetes : total cholesterol ( tc ) of < 4 mmol / l , ldl - c of < 2.0\nmmol / l , hdl - c of > 1.0 mmol / l ( male ) or hdl - c > 1.2 mmol / l ( female ) , and fasting tg of < 1.7 mmol / l.11 due to the relatively small numbers of patients receiving combination therapy or monotherapy with lipid - lowering drugs other than statins , this analysis focused on target attainment among patients taking statin monotherapy .\ndescriptive statistics were performed using microsoft excel 2010 ( microsoft , redmond , wa ) .\ndue to limitations in the demographic data ( see discussion ) , inferential and comparative statistical analyses were not performed .\nthe audit captured data on 14,652 patients with diagnosed diabetes from 40 practices . on average ,\n89.5% ( n = 13,108 ) had t2 dm ( median age : 66 years old , range : 17106 ; 44.7% female ) .\napproximately one - fifth ( 22.2% ; 2916 ) of the total t2 dm cohort had not received a prescription for lipid - lowering therapy during the 4 months before the audit .\nfor example , only around one - fifth were within the target values for total cholesterol and ldl - c . of patients with t2 dm who received lipid - lowering therapy , 94.7% ( 9647 )\napproximately half of the patients who received statin monotherapy attained the esc treatment targets for total cholesterol , ldl - c , hdl - c , or tg ( table 3 ) .\nindeed , irrespective of the individual statin used , around half of patients receiving statin monotherapy attained the esc treatment targets ( table 2 ) .\ntable 4 summarizes the dose distribution of each statin in t2 dm patients taking monotherapy .\nthe audit captured data on 14,652 patients with diagnosed diabetes from 40 practices . on average ,\n89.5% ( n = 13,108 ) had t2 dm ( median age : 66 years old , range : 17106 ; 44.7% female ) .\napproximately one - fifth ( 22.2% ; 2916 ) of the total t2 dm cohort had not received a prescription for lipid - lowering therapy during the 4 months before the audit .\nfor example , only around one - fifth were within the target values for total cholesterol and ldl - c .\nof patients with t2 dm who received lipid - lowering therapy , 94.7% ( 9647 ) received statin monotherapy , which was usually simvastatin or atorvastatin ( table 2 ) .\napproximately half of the patients who received statin monotherapy attained the esc treatment targets for total cholesterol , ldl - c , hdl - c , or tg ( table 3 ) .\nindeed , irrespective of the individual statin used , around half of patients receiving statin monotherapy attained the esc treatment targets ( table 2 ) .\ntable 4 summarizes the dose distribution of each statin in t2 dm patients taking monotherapy .\nthis large , cross - sectional , observational , systematic audit showed that , first , dyslipidemia is common among people with t2 dm in the uk and , secondly , that lipid concentrations generally and tg in particular remain elevated despite statin monotherapy .\nindeed , just over a fifth of t2 dm patients were not receiving lipid - lowering therapy , despite up to approximately 80% of these subjects showing evidence of dyslipidemia ( table 1 ) .\npersistent hypertriglyceridemia was common , occurring in half of those on statin monotherapy ( table 2 ) .\nthis audit is , as far as the authors are aware , the first large study performed solely from the perspective of primary care in the uk that assesses triglyceride concentrations in patients with t2 dm receiving statin monotherapy .\nthe results confirm the findings of the dyslipidemia international study ( dysis ) , which stratified patients according to the presence or absence of cvd . in patients with diagnosed cvd\n, 37.5% did not reach the ldl - c target , 38.3% were not at the hdl - c target , and 49.1% did not achieve the triglyceride target . among patients without cvd ,\nthe proportions were 45.0% , 30.4% , and 44.8% respectively . only around a quarter ( 25.2% and 25.8% with and without cvd , respectively ) achieved all three targets.9 in another study , 20.9% of 182 patients with t2 dm taking statins showed hypertriglyceridemia ( 2.3\n< 2.5 mmol / l ( 13.7% ) , ldl - c < 2.0 mmol / l ( 8.8% ) , and hdl - c 0.9 mmol / l ( 6.0%).10 in the present study , simvastatin 40 mg was the most frequently prescribed statin dose .\nhowever , 35.2% of simvastatin users took 20 mg or less , 24.7% of atorvastatin users took 10 mg , 28.2% of pravastatin users took 20 mg , and 72.2% of rosuvastatin users took 10 mg or less ( table 4 ) .\nfor example , simvastatin was the most widely prescribed statin in the dysis , in which the most common regimen was 2040 mg / day simvastatin equivalent.9 in a swedish study , 76% of simvastatin users took 20 mg or less , 48% of atorvastatin users took 10 mg , 55% of pravastatin users took 20 mg , and 76% of rosuvastatin users took 10 mg or less.12 the cross - sectional nature of the present audit and lack of clinical detail about each patient precluded an examination of any dose response relationship with statins or ascertaining of whether the low dose was clinically justified ( eg , due to concurrent conditions or adverse events ) .\nnevertheless , the data and previous studies suggest that a considerable proportion of patients receives low doses of statin and , as a result , may be undertreated .\nas such , there may be scope to intensify statin regimens in many t2 dm patients with dyslipidemia who are managed in primary care .\nthe major limitation of this study is the absence of any information regarding the possible contribution made by potential confounders ( such as coexisting obesity , dietary issues , secondary hypertriglyceridemia , impaired renal and hepatic function , and suboptimal glycemic control ) to the suboptimal management of triglyceride levels .\nfor example , more potent statins ( atorvastatin , rosuvastatin , and pitavastatin ) produce a robust lowering of tg , especially at high doses and in patients with hypertriglyceridemia.13 however , in this audit , a numerically smaller proportion of patients receiving more potent statins ( atorvastatin and rosuvastatin ) attained the treatment targets than those taking simvastatin .\nsimilarly , the nature of the audit meant that we could not ascertain whether the subjects had relatively treatment - resistant dyslipidemia or were in the titration phase , or whether there were any differences between patients receiving statins and the group that did not receive any lipid - lowering medication .\nmoreover , we could not correlate hba1c levels or compliance with hypoglycemic medication with use of statins or triglyceride levels .\nhowever , the present study is based on data from a large number of patients and , therefore , probably accurately represents the proportions of people with t2 dm who attain lipid targets currently in uk primary care . as such , the audit underscores the need to ascertain the reasons why patients failed to attain the treatment targets and to consider intensified intervention .\nthe esc guidelines specify treatment targets based on fasting triglyceride levels . however , the audit was unable to ascertain whether triglyceride levels were measured in the fed or fasting state .\nhowever , postprandial lipids , partially hydrolyzed chylomicron , and very - ldl remnants apparently accelerate atherogenesis by exacerbating endothelial dysfunction , augmenting numbers of atherogenic small ldl particles , and promoting thrombosis and inflammation .\narguably , therefore , postprandial tg more accurately predict vascular risk than fasting levels.14 as a result , both fed and fasting hypertriglyceridemia are associated with increased cvd risk .\nthe high prevalence of hypertriglyceridemia identified in this audit suggests that tg are often undertreated .\nnumerous secondary causes including hypothyroidism , renal impairment , hepatic inflammation , and poor glycemic control may increase tg and should be diagnosed and managed.15 however , in this study , the number of patients who had secondary hypertriglyceridemia and the extent to which concurrent conditions influenced the likelihood of attaining the treatment targets could not be assessed . despite these caveats , the results of the present study have implications for management .\nfor example , clinicians should continue to emphasize that all patients should follow dietary advice and exercise regularly to improve glycemic control and lipid profiles , as well as implementing interventions to optimize compliance with lifestyle changes , and lipid - lowering and other medications .\nthe audit showed that relatively few patients with t2 dm received statins in combination with ezetimibe , fibrate , omega 3 polyunsaturated fatty acids , or nicotinic acid .\nas many patients show dyslipidemic profiles that are associated with an increased risk of cvd despite statin treatment , clinicians need to consider intensifying statin regimens , offering additional lipid - modifying therapies generally , or regimens specifically aimed at lowering tg levels ( such as pharmaceutical grade , highly purified omega 3-acid ethyl esters ) , particularly to improve the management of diabetic dyslipidemia .\nt2 dm patients managed in uk primary care commonly show persistent lipid abnormalities . in this study , over a fifth of t2 dm patients were found to be not receiving lipid - lowering therapy .\nclinicians need to implement interventions to optimize compliance with lipid - lowering and other medications .\nclinicians also need to consider intensifying statin regimens , prescribing additional lipid - modifying therapies , and specific treatments aimed at triglyceride lowering to improve dyslipidemia control in statin - treated patients with t2 dm .", "answer": "purposethis paper reports the results of an audit that assessed the prevalence of residual hypertriglyceridemia and the potential need for intensified management among patients with statin - treated type 2 diabetes mellitus ( t2 dm ) in primary care in the uk.patients and methodsa cross - sectional , observational , systematic audit of patients with diagnosed diabetes from 40 primary care practices was undertaken . \n the audit collected basic demographic information and data on prescriptions issued during the preceding 4 months . \n t2 dm patients were stratified according to the proportion that attained european society of cardiology treatment targets.resultsthe audit collected data from 14,652 patients with diagnosed diabetes : 89.5% ( n = 13,108 ) of the total cohort had t2 dm . \n of the people with t2 dm , 22.2% ( 2916 ) were not currently receiving lipid - lowering therapy . \n up to approximately 80% of these people showed evidence of dyslipidemia . among the group that received lipid - lowering therapy , 94.7% ( 9647 ) were on statin monotherapy , which was usually simvastatin ( 69.5% of patients receiving statin monotherapy ; 6707 ) . \n the currently available statins were prescribed , with the most common dose being 40 mg simvastatin ( 44.2% ; 4267 ) . \n irrespective of the statin used , around half of the patients receiving statin monotherapy did not attain the european society of cardiology treatment targets for triglycerides , low - density lipoprotein , high - density lipoprotein , and total cholesterol.conclusiont2dm patients managed in uk primary care commonly show persistent lipid abnormalities . \n clinicians need to optimize compliance with lipid - lowering and other medications . \n clinicians also need to consider intensifying statin regimens , prescribing additional lipid- modifying therapies , and specific treatments aimed at triglyceride lowering to improve dyslipidemia control in statin - treated patients with t2 dm .", "id": 425} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 36 year old , para 2 female with a history of chronic right adnexal pain was admitted for a laparoscopic right salpingo - oophorectomy .\nthe patient experienced worsening right ovarian pain which did not improve despite nonsteroidal anti - inflammatory medications .\nan ultrasound revealed a 4 cm complex ovarian mass which did not change in size with serial ultrasounds .\nprevious surgeries included an abdominal hysterectomy for a fibroid uterus , laparoscopic left salpingooophorectomy and lysis of adhesions for pelvic pain , an appendectomy , two previous cesarean sections , a bilateral tubal ligation and an inguinal herniorrhapy as a teenager .\nthe patient underwent general endotracheal anesthesia and was prepped and draped in the usual manner after being placed in the dorsolithotomy position . after making a small incision in the umbilicus\n, a veress needle with its 2 mm trocar was carefully inserted into the abdomen with the panniculus elevated .\nthe saline drop test revealed patency , and the veress needle was attached to the co2 for the pneumoperitoneum .\nthe co2 was immediately stopped , the veress needle removed and a 2 mm microlaparoscope ( minisite gold ; u.s .\nsurgical corp . , norwalk , ct ) inserted into the trocar , which revealed bowel lumen with stool .\na second 2 mm trocar was placed in the right lower quadrant , and the microlaparoscope revealed a perforation into the anti - mesenteric border of the ileum .\nwas inserted under direct visualization lateral to the right rectus muscle at the level of the umbilicus .\nthe 2 mm umbilical trocar was replaced with a new one of the same diameter . at the site of the small bowel entry ,\nafter irrigating the pelvic and abdominal cavities with 3 liters of normal saline with no further fecal spillage or bleeding , the decision was made to not suture the site of entry into the small bowel .\npostoperatively , the patient had a nasogastric tube inserted , was placed on famotidine ( pepcid ) 20 mg every 12 hours and was given antibiotics consisting of ampicillin , gentamicin and clindamycin intravenously .\non the evening of surgery , the patient developed a fever of 101.2 degrees fahrenheit .\non postoperative day one , she had a single temperature spike of 100.9 after being afebrile .\non postoperative day three , she had a small bowel movement , was advanced to a regular diet and discharged home in the afternoon on oral cephalexin . at her\none week postoperative visit she remained afebrile , tolerating her diet and with no complaints .\none month after surgery she was symptom free and her chronic right adnexal pain was gone .\nmost of the current data on laparoscopic complications is based on case reports and small series .\nopen laparoscopy was developed to reduce the risk of blind entry into the peritoneal cavity .\nhowever , injury to the bowel has been reported to occur at the same rate with this technique .\nrecent advances in microlaparoscopy have allowed us to perform both diagnostic and operative procedures through 2 mm trocars . in our patient ,\na microlaparoscope inserted through the entry site confirmed the complication . had we performed traditional laparoscopy using a 10 mm trocar , the site of bowel injury would have required suturing , possibly a laparotomy . in cases where the site of perforation is free of adhesions and in need of repair\n, the bowel can be sutured externally by withdrawing the bowel through a 12 mm trocar .\nour minimally invasive , conservative approach to this complication was possible because no further fecal material leaked through the site of perforation and the diameter of the injury was small .\nwe felt that suturing in this case was unnecessary because the margins were regular , hemostatic and self - sealing .\nthe stool that was forced through this site probably was a result of the increased intraluminal pressure in the bowel from the co2 insufflation .\nafter copious irrigation with normal saline and no further spillage , we felt that the patient 's morbidity would be greater with suturing of the bowel if it produced bleeding or further spillage .\nexcept for an initial fever , the patient responded well to conservative management with bowel decompression , antibiotic therapy and close observation .\nconditions requiring a laparotomy following a bowel perforation include any sign of peritonitis , persistent fever , ileus or prolonged vomiting .\nwe believe that some small bowel perforations from 2 mm instrumentation can be managed conservatively without suturing provided that the site of injury is not actively leaking stool nor bleeding .", "answer": "although laparoscopy is one of the most common surgical procedures done today , bowel perforations can and do occur during the initial insertion of the veress needle and/or trocar . \n recent advances in microlaparoscopy have reduced the morbidity of this complication when encountered . \n we report a case of small bowel perforation following insertion of a veress needle with its 2 mm trocar and our minimally invasive intra - operative and postoperative management of the patient .", "id": 426} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute coronary syndrome ( acs ) is characterized by acute , regional reductions in coronary blood flow and myocardial ischemia .\nacs describes a spectrum of clinical manifestations , including unstable angina ( ua ) , non - st - segment elevation myocardial infarction ( nstemi ) , and st - segment elevation myocardial infarction ( stemi ) [ 13 ] .\natherosclerosis is a chronic inflammatory disease of the arterial wall , characterized by endothelial dysfunction , intimal hyperplasia , and smooth muscle proliferation , as well as deposition of lipids and formation of microvessels within the vascular wall [ 1 , 46 ] .\nendothelial dysfunction is accompanied by the expression of adhesion molecules ( such as the vascular cell adhesion molecule- ( vcam- ) 1 ) [ 7 , 8 ] and chemokines [ 4 , 9 ] .\nthe recruitment of inflammatory cells is triggered by the production of cytokines ( such as il-1 , il-6 , il-8 , tnf- , and ccl2 ) within the plaque microenvironment .\nchemokines are released from endothelial cells , mast cells , platelets , macrophages , and lymphocytes .\nthe macrophage migration inhibitory factor ( mif ) is a molecule that consists of 115 amino acids ; it was described as the main cytokine involved in attracting immune cells such as macrophages and t and b cells [ 12 , 13 ] .\nthe secretion of mif by inflammatory cells can be induced by exposure to oxidized low - density lipoprotein or other cytokines , such as tnf- and interleukin - c [ 13 , 14 ] .\nmif activates the expression of various proinflammatory cytokines and chemokines and recruits macrophages to the site of atherosclerosis .\nmif participates in the pathogenesis of inflammatory and atherosclerosis processes [ 12 , 13 , 1517 ] .\nthe mif gene is located at 22q11.2 and contains several polymorphisms , including the rs5844572 .\nthis genetic marker is a catt short tandem repeat ( str ) at position 794 , with five to eight length variants ( alleles 5 to 8) .\nthere is an association between the length of the repeats and the expression of the genetic marker ; the higher alleles ( catt6 , catt7 , and catt8 ) show higher expression of the gene . since mif is an inflammatory mediator and\ngiven the role of genetic factors that modify its expression , mif could contribute to atherosclerosis and susceptibility to acs .\nthe aim of this study was to investigate the association between the 794 ( catt)58 mif gene polymorphism and susceptibility to acs in a western mexican population .\nthe study group included 200 acs unrelated patients recruited from hospital de especialidades del centro mdico nacional de occidente del instituto mexicano del seguro social ( cmno - imss ) and classified according to the criteria of the american college of cardiology ( acc ) .\nas a control group , 200 unrelated healthy subjects ( hs ) were recruited from the general population of western mexico .\nwe applied a standardized questionnaire to the hs group and applied routine laboratorial clinical assessments to detect any potential alterations , and those subjects with any clinical alterations were excluded of the study .\nwe considered mexican mestizo subjects , only those individuals who for three generations , including their own , had been born in western mexico .\nthe study conforms to the ethical principles contained in the declaration of helsinki , and ethical approval was obtained from centro universitario de ciencias de la salud , cucs , udeg ( c.i .\ngenotyping of the str 794 ( catt)58 polymorphism was achieved by conventional pcr and polyacrylamide gel electrophoresis using the primers reported by radskate et al . .\ncycling conditions were as follows : an initial denaturation at 95c for 4 min followed by 30 cycles of 30s at 95c , 30s at 60c , and 30s at 72c and then a final extension of 2 min at 72c .\nallele identification was done by using a 10-bp ( invitrogen ) and homemade allelic ladders containing pooled samples .\nin addition , as genotyping control , automatized sequencing of one random sample of each homozygote genotype allowed confirmation of results ( abi prism 377 genetic analyzer , applied biosystems , foster city , ca , usa ) .\nthe hardy - weinberg equilibrium test and genotype and allele frequencies were calculated by the chi - square test or fisher 's exact test , when applicable .\nodds ratios ( or ) and 95% confidence intervals ( 95% ci ) were calculated to test the probability that the genotype and allele frequencies were associated with acs . a p value < 0.05 was considered to be statistically significant .\nstudy the sample size was calculated according to the minor allele frequency of the 794 ( catt)58 mif gene polymorphism reported in mexican mestizo population by llamas - covarrubias et al . \nit means that in order to detect differences , we needed at least 82 individuals each group with 95% confidence interval and statistical power of 80% . in this respect 200 individuals were included exceeding by far the required sample size .\nthe median age of hs and acs groups was 61 and 63 years , respectively .\nthe most prevalent clinical diagnosis in the acs group was stemi ( 76% ) , while obesity was the most common risk factor ( 61% ) , followed by high blood pressure ( hbp : 60% ) .\nalso , in the acs group other clinical parameters such as troponin i ( tni ) , troponin t ( tnt ) , creatine phosphokinase ( cpk ) , and creatine kinase ( ck ) were evaluated in order to find a possible genetic association .\nhowever , we did not find any statistical association with 794 ( catt)58 mif gene polymorphism .\nno deviation from the hardy - weinberg equilibrium was detected in the 794 ( catt)58 mif polymorphism ( p = 0.16 ) .\nthe allele and genotype frequencies in both the acs and hs groups are shown in table 2 .\nallele 6 was the most frequent in both groups ( acs : 54% and hs : 57% ) .\nthe most common genotypes in acs and hs subjects were 6/7 and 6/6 , respectively .\na significant association was found between the 6/7 genotype and susceptibility to acs ( 68% versus 47% in acs and hs , resp . ,\nwe also stratified the main risk factors for development of acs by genotype ( table 3 ) . despite no significant differences\n, we observed that the 6/7 genotype was the most frequent in each subgroup and that the 5/5 genotype was the less common .\nacute coronary syndrome is a multifactorial disease arising through a combination of both environmental and genetic risk factors .\nseveral studies have reported a relationship between atherosclerosis and acs [ 8 , 22 ] .\nactivated endothelial cells express adhesion molecules and favor the recruitment of monocytes to the endothelium .\nthese in turn release proinflammatory cytokines including il-1 , il-6 , tnf- , and mif .\nreported a correlation between the expression of mif and an increased intima - media thickness and also with lipid deposition in carotid artery plaques ; white et al . reported a proinflammatory role for mif in acute myocardial infarction ; mller et al .\nthis genetic marker has five to eight variants ( catt)58 . a higher repeat number is associated with an increase in the gene expression . in the present research , we reviewed the association of the 794 ( catt)58 mif polymorphism with acs in mexican mestizo individuals .\nthe genotype and allele frequencies were distributed in a similar way to a previous study with a mexican mestizo population by llamas - covarrubias et al . .\nwe also compared the frequencies with those of caucasian american and african american populations and observed that the genotype frequencies in our population differed from them ; they found that the genotype 6/6 was the most frequent , while the 5/8 and 6/8 genotypes were less frequent in caucasian americans and african americans , respectively .\nin addition , a statistical difference was found in genotypic and allelic distributions when compared with an african ethnic group where the 5/6 genotype and the 5 allele showed the highest frequency ; these differences could be attributed to the ancestry of the population .\nthe mexican mestizo population is a crossbreed of amerindian , european , and african populations , with an estimated contribution of 2125% , 6064% , and 15% , respectively ( rubi - castellanos , 2009 ) . in this study\n, we found an association between the 6/7 genotype of the mif 794 ( catt)58 polymorphism and susceptibility to acs in a western mexican population .\nthere is also another single nucleotide polymorphism in the promoter of the mif gene at the position 173 that has been previously analyzed and related to the inflammatory response in coronary bypass surgery and coronary alterations in children with kawasaki disease .\nrecent studies support the fact that mif is a pleiotropic cytokine mainly released from macrophages that has been shown to be increasingly expressed during atherogenesis , oxldl being a major inducer [ 14 , 23 , 24 ] .\nacs is a pathology where inflammation favors the recruitment of monocytes to the atherosclerotic plaque ; otherwise , new studies have described the functional effect of mif 794 ( catt)58 , showing that the catt5 allele has the lowest transcriptional activity and the catt68 alleles increase the expression rate .\nthis evidence validates the association found between the 6/7 genotype of the mif 794 ( catt)58 polymorphism and susceptibility to acs .\nrecently , chen et al . showed that the transcriptional repressor hbp1 ( hmg box - containing protein 1 ) negatively regulates mif expression , but this is still under investigation .\nwe also stratified the risk factors in the acs group regarding the genotypes of the 794 ( catt)58 mif polymorphism .\nas we mentioned , mif has an important function in inflammatory processes ( kleemann et al . ) , suggesting that mif controls the development of metabolic pathologies associated with acs risk factors such as obesity and type 2 diabetes mellitus .\nnevertheless , we did not find any association between the genotypes of the 794 ( catt)58 mif polymorphism and the risk factors in the acs group .\nhowever a trend is shown between the 6/7 genotype and obesity , type 2 diabetes mellitus , dyslipidemia , and high blood pressure .\nwe want to highlight that , as a limitation of the study , the sample size in each subgroup is not enough to find an association , but there is a marked tendency with the higher alleles , which are responsible for a higher expression .\nit is worth noting that the 794 ( catt)58 promoter polymorphism of mif has not been studied in relation to susceptibility to acs .\nthe 6/7 genotype of the mif 794 ( catt)58 polymorphism is related with susceptibility to acs in a western mexican population .", "answer": "the macrophage migration inhibitory factor ( mif ) is related to the progression of atherosclerosis , which , in turn , is a key factor in the development of acute coronary syndrome ( acs ) . \n mif has a catt short tandem repeat ( str ) at position 794 that might be involved in its expression rate . \n the aim of this study was to investigate the association between the 794 ( catt)58 mif gene polymorphism and susceptibility to acs in a western mexican population . \n this research included 200 acs patients classified according to the criteria of the american college of cardiology ( acc ) and 200 healthy subjects ( hs ) . \n the 794 ( catt)58 mif gene polymorphism was analyzed using a conventional polymerase chain reaction ( pcr ) technique . \n the 6 allele was the most frequent in both groups ( acs : 54% and hs : 57% ) . \n the most common genotypes in acs patients and hs were 6/7 and 6/6 , respectively , and a significant association was found between the 6/7 genotype and susceptibility to acs ( 68% versus 47% in acs and hs , resp . , \n p = 0.03 ) . \n we conclude that the 6/7 genotype of the mif 794 ( catt)58 polymorphism is associated with susceptibility to acs in a western mexican population .", "id": 427} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nosteochondral lesions involve the articular cartilage and underlying subchondral bone , and most often affect the knee and the talus ( 1 ) .\nosteochondral lesions of the femoral head are uncommon , and few studies have reported the imaging findings of such lesions . since this condition occurs in relatively young patients , and osteochondral damage puts joints at high risk of subsequent degeneration ( 2 ) , timely recognition of this disorder is important for proper treatment . herein , we review previous literature related to osteochondral lesions of the femoral head and 796report a case in which lesion involving the bilateral femoral heads was observed .\nthis lesion manifested as subchondral cysts according to the initial radiography images , and led to further evaluation by computed tomography ( ct ) arthrography and immediately obtained magnetic resonance imaging ( mri ) scan that revealed overlying articular cartilage defects .\na 20-year - old female patient was referred to our hospital from a local hospital .\nher chief complaint was pain in both hips along with severe right side pain of approximately 2 months duration .\nnotably , however , she had been a taekwondo athlete in high school for several years . on clinical examination ,\nplain radiography of the hip showed well - defined subchondral radiolucent lesions with a subtle sclerotic rim in the superior portion of the right femoral head ( fig .\nthe acetabuli in both sides of the hip displayed mild dysplasia with lower limit of normal ( center - edge angle , 24 - 25 degrees ) .\nno signs of degeneration , such as joint space narrowing or juxta - articular sclerosis , were observed , except for subtle osteophyte around the head - neck junction of the right femur .\ndeformations of the femoral head , such as flattening , or the presence of crescent signs were also absent .\nbased on imaging findings , a provisional diagnosis of avascular necrosis with subchondral cysts could not be excluded . to further investigate the lesion ,\n1b , c ) revealed several subchondral cysts that were hypointense on the t1-weighted images ( repetition time [ tr]/echo time [ te ] , 374/20 ) and hyperintense on the t2-weighted fat - suppressed images ( tr / te , 1500/29 ) .\nthe overlying portion in this region revealed a focal articular cartilage defect measuring about 10 15 mm in size , consistent with an osteochondral lesion .\nno surrounding bone marrow edema was observed , and no cartilage damage was noted on the opposite site of the acetabulum .\nthe scintigraphy scan with 99 m technecium methylene diphosphonate showed no increased activity in the femoral head .\non arthroscopy , chondral damage was noted in the superior portion of the femoral head .\nfollow - up plain radiography of the hip performed about a year later revealed subchondral cysts in the superior portion of the left femoral head ( fig .\nthe patient reported no incidence of trauma in the meantime , other than mild hip discomfort .\n1f ) scans of the left hip also showed several subchondral cysts , measuring about 14 13 mm in size , with associated overlying articular cartilage loss .\nretrograde inspection of previous hip mri scans performed at the local referral hospital 2 months before the first visit to our hospital revealed lesions of the left femoral head with abnormal signal intensity , including hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images ( fig .\nthis led us to hypothesize that the subchondral cyst lesion had progressed from a pre - existing lesion already present one year before .\nthe chondral defect was confirmed by arthroscopy and core decompression with a bone graft was performed , as had been done for the right side .\nosteochondral lesions involve articular cartilage and the underlying subchondral bone , and mainly affect the knee and the talus ( 1 ) .\nosteochondral lesions of the femoral head are rare and the prevalence is unclear ( 3 ) .\ndetailed reports of the imaging findings of such lesions are also quite limited . therefore , osteochondral lesions of the femoral head can be easily overlooked , unless radiologists are suspicious of osteochondral lesions that develop in the femoral region .\nfurthermore , osteochondral lesions of the femoral head are known to cause joint degeneration ( 2 ) .\nwe diagnosed the osteochondral lesion by identifying the accompanying overlying articular cartilage defects by ct arthrography and mri , which were performed for further evaluation .\nwe excluded a diagnosis of avascular necrosis due to the absence of a double line sign or a crescent sign of the femoral head on mri .\nmoreover , no signs indicative of primary osteoarthritis , such as joint space narrowing or juxta - articular sclerosis in both the acetabulum and femoral head , were observed .\nthe causes of osteochondral lesions have not yet been elucidated , and are likely to be multifactorial ( 4 ) .\none of the well - known causes of the osteochondral lesion of the femoral head is legg - calv - perthes disease . in this secondary lesion\n, however , separated subchondral bone with articular cartilage from the joint surface is the main feature , which is different than our case .\nother etiologies of osteochondral lesions in the hip include previous infection , genetics , ischemia or trauma ( 5 , 6 ) .\nmany studies have reported damages incurred by repetitive traumas ( 7 , 8 , 9 ) .\n( 10 ) reported normal plain radiographic finding but mri detection of a subchondral lesion in an athlete with continuous hip pain , and suggested that although an athlete may not recall a specific incidence of past trauma , shearing injury of the cartilage by subluxation during joint rotation or impact damage caused by forces exerted by jumping could have occurred .\n( 7 ) demonstrated that osteochondritis dissecans of the elbow can result from articular cartilage damage inflicted by repeated trauma .\nnakamura et al . ( 6 ) reported an osteochondral lesion of the femoral head believed to have originated from repeated impact and high axial loads in a fencer .\nour patient was previously an athlete , and so could have developed the osteochondral lesions by repetitive trauma , despite the lack of recollection of any particular past trauma .\n( 10 ) also reported abnormal bone marrow signals from an osteochondral lesion on the femoral head .\nthis lesion exhibited hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images , along with cartilage surface irregularities of the medial portion . in our case , although the cartilage surface irregularities were not immediately apparent from the previous mri scans taken at the local referral hospital , lesions displaying hypointensity on the t1-weighted images and hyperintensity on the t2-weighted images were present in the left femoral head .\nan articular cartilage defect lesion accompanied by subchondral cysts was found about a year later , similar to the lesion previously observed on the right femoral head .\nwe concluded that an osteochondral lesion was already present at the time of the previous mri scan , and that this lesion progressed to the lesion with subchondral cysts .\nit may often be necessary to distinguish osteochondral lesions from avascular necrosis in differential diagnoses .\nthe articular cartilage of the femoral head has been shown to be unaffected in the majority of cases of avascular necrosis , whereas this cartilage is often damaged in osteochondral lesions . moreover ,\navascular necrosis of the femoral head manifests itself as a somewhat broader lesion , often accompanied by serpiginous , low signal lines or crescent signs ( 11 ) . on the other hand ,\nosteochondral lesions often reveal smaller - sized areas with wedge - shaped signal abnormalities , or a narrow inlet with deep nest - shaped lesions , as seen in this case ( 12 , 13 ) .\npatient age , in particular being younger , is also helpful in distinguishing this condition from avascular necrosis ( 10 ) .\n10 ) are thought to be indicative of lesions in the acute or subacute stage . in the chronic stage , however , a progressed degenerative bony lesion in the form of subchondral cysts , as seen in our case , or perhaps even a sclerotic change exhibiting hypointensity on the t1- and t2-weighted images , may be observed ( 6 ) . although some authors have reported that high uptake on the scintigraphy represents inflammation or lesion healing , no increased uptake was observed in our case , probably because the lesions are in the chronic stage .\nin addition , young patients , especially those with a previous trauma or a history of being an athlete , are potential candidates for osteochondral lesions .\nradiologists should look for bony lesions associated with articular cartilage defects in the femoral head , which could be indicative of an osteochondral lesion , similar to the lesions that are known to occur in the knee or the talus .", "answer": "osteochondral lesions of the femoral head are uncommon and few studies have reported their imaging findings . \n since joints are at risk of early degeneration after osteochondral damage , timely recognition is important . \n osteochondral lesions of femoral head may often be necessary to differentiate from avascular necrosis . here , we report a case of osteochondral lesions on bilateral femoral heads . \n this lesion manifested as subchondral cysts in initial radiographs , which led to further evaluation by computed tomography arthrography and magnetic resonance imaging , which revealed overlying cartilage defects .", "id": 428} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunless otherwise stated , all chemicals and solvents were purchased from commercial suppliers in reagent- or technical - grade quality and used directly as received without further purification .\nthe bis(arylimino)acenaphthene ligands were prepared from acenaphthenequinone and the corresponding substituted anilines in anology to literature methods.[14 , 27 ] the rhenium complex 1 was synthesized as previously reported .\ngeneral procedure for the preparation of 2 and 3 : equimolar amounts of re(co)5cl ( 0.05 g , 0.14 mmol ) and the corresponding bis(arylimino)acenaphtene ligand were refluxed in dry toluene ( 4 ml ) for 30 min .\ncomplete precipitation of the product was obtained upon cooling the reaction mixture to room temperature and slow addition of n - hexane .\nas a service to our authors and readers , this journal provides supporting information supplied by the authors .\nsuch materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors", "answer": "rhenium(i ) carbonyl complexes carrying substituted bis(arylimino)acenaphthene ligands ( bian - r ) have been tested as potential catalysts for the two - electron reduction of carbon dioxide . \n cyclic voltammetric studies as well as controlled potential electrolysis experiments were performed using co2-saturated solutions of the complexes in acetonitrile and acetonitrile water mixtures . \n faradaic efficiencies of more than 30 % have been determined for the electrocatalytic production of co. the effects of ligand substitution patterns and water content of the reaction medium on the catalytic performance of the new catalysts are discussed .", "id": 429} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe ultrasound ( us ) appearance of testicular microlithiasis ( tm ) was first described by doherty et al . in 1987 .\nthe prevalence of tm in symptomatic korean men was found to be 6.0% with significant co - occurrence of tm , testicular cancer , and infertility by yee et al . \nalthough the cause - and - effect relationships are unclear , tm has been seen in patients with cryptorchidism , varicoceles , infertility , testicular torsion , klinefelter syndrome , pulmonary alveolar microlithiasis , neurofibromatosis , acquired immunodeficiency syndrome , intratubular germ cell neoplasia , and most importantly , primary testicular neoplasms .\nreported that 74% of testes with tumors had associated ipsilateral tm on radiological inspection ; whereas , only 8% of testicular specimens with benign conditions had microcalcifications .\nalthough chen et al . reported that there was a significant difference in the rate of malignancy in males with tm compared with those without tm , the question remains whether tm independently increases the risk of testicular malignancy in taiwanese men .\n, after reporting an association between tm and testicular tumor specimens , suggested in 1982 that radiographic studies be incorporated into diagnosing tm because of the perceived risk for testicular cancer in testicles with microlithiasis\nperformed us follow - up in 9 of 22 patients with tm for a mean of 32 months without any newly developing tumors being diagnosed .\nreported similar results ; therefore , a regular scrotal us is controversial in asymptomatic tm patients .\nthe current recommendations , including those of the european association of urology , are that the presence of microlithiasis alone is not an indication for a regular scrotal us in the absence of other risk factors ( size<12 ml or atrophy , inhomogeneous parenchyma ) .\nhowever , there have been no reports describing the changes in calcification over time in pediatric patients with tm .\nthe study protocol was approved by the institutional review board of the asan medical center .\nthe medical records from july 1997 to august 2014 of the asan medical center , a tertiary referral center , were retrospectively screened for patients diagnosed with tm by scrotal us .\ntwenty - three tm patients were included who had undergone scrotal us at least twice .\nwe analyzed the patient characteristics , clinical manifestations , specific pathological features , and clinical outcomes .\nwe measured the calcified area in maximum cross - sectional area , and we compared the calcific density in the initial diagnostic us and the final follow - up us .\nwe defined the testis and the calcified area in terms of their maximal cross - sectional area and calculated those areas using image j software ( national institutes of health , bethesda , md , usa ) ( fig .\npatients that showed microlithiasis in three or more sections were defined as diffuse type , and patients with microlithiasis in less than three sections were defined as focal type ( fig .\nwe classified the patients into three groups according to the change of microlithiasis : an increased group , 20% increase in microlithiasis ; a decreased group , 20% decrease in microlithiasis ; and a no change group , < 20% increase or decrease .\ndifferences were analyzed by a paired t - test , and crosstabs were used to assess dependent samples . in this study p - values < 0.05 were considered statistically significant .\nthe mean age at presentation was 11.34.6 years , and the follow - up period ( interval of fist us and last us ) was 79.138.8 months ( range , 25.4 - 152.9 months ) .\nthe mean age at last follow - up was 17.85.8 years ( range , 6.4 - 26.9 months ) .\nfollow - up occurred for 19 of 23 patients over puberty ( defined as > 13 years old ) .\nof the 23 patients 20 had bilateral tm , 2 patients had unilateral tm , and 1 patient had an atrophic testis .\nless frequent comorbid conditions included testicular torsion ( 3 patients , 13.0% ) , epididymitis ( 3 patients , 13.0% ) , varicocele ( 2 patients , 8.7% ) , hydrocele ( 2 patients , 8.7% ) , and epididymal cyst ( 2 patients , 8.7% ) .\ncalcific density was increased at the last follow - up us compared with the initial us ; however , this finding was not statistically different ( 3.74%6.0% vs. 3.06%4.38% , respectively , p=0.147 ) .\nwe divided the subjects into two groups ( focal vs. diffuse ) based on the distribution of tm .\nwe classified 23 testes as having focal tm and 20 testes as having diffuse tm .\nin focal tm calcific density decreased but not significantly ( 0.72%0.55% vs. 0.66%1.03% , p=0.813 ) . on the other hand ,\nthe calcific density of diffuse tm show a trend toward increase ( 5.8%5.2% vs. 7.3%7.4% , p=0.457 ) ( table 2 ) ( fig .\n3 ) . to clarify the tendency of tm calcification toward increase vs. decrease we divided the subjects into three groups based on the calcific density change of tm ( increase : increased > 20% ; decrease : decreased > 20% ; no change : < 20% increase or decrease ) .\nwe categorized 14 testes as increased , 18 testes as decreased , and 11 testes as no change .\nhalf of the patients with diffuse tm were assigned to the increased group , a proportion significantly higher than focal tm ( 10/20 [ 50% ] in diffuse tm , 4/23 [ 17.4% ] in focal tm , p=0.049 ) ( table 3 ) .\nin addition , 5 of 8 testes with cryptorchidism ( including 2 with bilateral cryptorchidism ) were categorized into the increased group .\nprevious tm studies have focused only on the relationship between tm and testicular cancer , and not on the natural course of this disease progression . in our current study , we report the natural course of calcific density changes in pediatric tm during pubertal development .\nthe mean age at presentation was 11.3 years and the mean follow - up period of approximately 5 years allowed follow - up of 23 patients over pubertal development . despite a follow - up interval that allowed potential pubertal changes to the testis , none of our patients developed testicular cancer or new abnormal symptoms . by contrast , there are some reported cases of patients with a known tm on us exam that eventually developed a primary testicular cancer .\nreported a yolk sac tumor developing in a 17-year - old boy being followed for bilateral tm that was originally detected because of an initial sonographic evaluation of unequal sized testes .\nreported the case of a man with tm seen on a sonograph performed due to bilateral testicular pain who presented three years later with a metastatic germ cell tumor of the left testicle .\nalthough , an association between tm and subsequent testicular tumors appears likely , whether there is a true cause - and - effect relationship remains unknown .\n( 7 patients , 45 months)-used us to follow patients with tm and , similarly to our present results , did not detect the appearance of new testicular tumors .\ncompared with these prior studies , our current study incorporates more patients and a longer - term follow - up extending through puberty .\nan additional strength of our study over previous studies is in our investigation of changes in calcified density of the tm .\none earlier study has reported nonquantitative changes in the prominence of tm on yearly us follow - up .\nthe tm was less prominent in one patient , unchanged in four , and two patients were lost to follow - up . to our knowledge , our present study is the first report to provide a quantitative analysis of calcific density in tm .\ncalcific density on us showed a nonstatistically significant trend toward increase over time in our study subjects .\nreported a relationship between the number of microliths and testicular cancer after subgrouping subjects into four ranges based on the number of microliths . in our present study , we divided tm into two nearly equal groups based on the distribution pattern of calcification ( focal type [ 23 testes ] vs. diffuse type [ 20 testes ] ) that appear to differ in terms of calcification trends .\ncalcific density shows a trend toward a decrease in focal tm but toward an increase in 50% of the testes with diffuse tm .\nnotably , the majority of testes ( 5/8 ) in our study series with cryptorchidism , including those with bilateral cryptorchidism , were categorized as being in the increased calcification group .\nduring the follow - up through puberty of the microlithiasis in the 23 boys in our present study , we observed no significant changes in the density of their microliths and no development of testicular cancer ; however , we found that diffuse tm and cryptorchidism tend to increase calcific density .\nhence , close observation is recommended in cases of tm combined with cryptorchidism and diffuse microlithiasis .", "answer": "purposetesticular microlithiasis ( tm ) is a relatively rare clinical entity of controversial significance characterized by the existence of hydroxyapatite microliths located in the seminiferous tubules . \n the aim of this study was to observe the natural course of changes in the calcific density of pediatric tm.materials and methodswe included a total of 23 tm patients undergoing scrotal ultrasound ( us ) on at least two occasions from july 1997 to august 2014 . \n we retrospectively analyzed the patient characteristics , clinical manifestations , specific pathological features , and clinical outcomes . \n we measured the calcified area and compared the calcific density between the initial and final uss.resultsthe mean age at diagnosis was 11.34.6 years , and the follow - up period was 79.138.8 months ( range , 25.4 - 152.9 months ) . during the follow - up period , \n no patients developed testicular cancer . \n calcific density on us was increased in the last versus the initial us , but not to a statistically significant degree ( 3.74%6.0% vs. 3.06%4.38% , respectively , p=0.147 ) . \n when we defined groups with increased and decreased calcification , we found that diffuse tm was categorized into the increased group to a greater degree than focal tm ( 10/20 vs. 4/23 , respectively , p=0.049 ) . \n in addition , five of eight cases of cryptorchidism ( including two cases of bilateral cryptorchidism ) were categorized in the increased calcification group.conclusionsdiffuse tm and cryptorchidism tend to increase calcific density . \n close observation is therefore recommended for cases of tm combined with cryptorchidism and cases of diffuse tm .", "id": 430} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchronic cough is a frequent presenting complaint to not only the general practitioner but also the otolaryngologist and respiratory specialist .\ndiagnosis can be difficult , especially in primary care , but empirical treatment for common causes such as asthma , chronic obstructive pulmonary disease , gastro - oesophageal reflux disease , postnasal drip or drug - induced cough ( most commonly secondary to angiotensin converting enzyme inhibition ) is recommended when there are no associated worrying symptoms , and is successful in the majority of cases .\nsymptoms that may signify a rarer but more serious cause for chronic cough include the copious production of sputum , fever , sweats , unintentional weight loss , haemoptysis , clubbing , hoarseness and marked dyspnoea . here\nwe highlight a unique cause of chronic cough : the initial symptom of lymphoma compressing the brainstem .\na 69year - old gentleman presented to his general practitioner with a 3-month history of progressive unsteadiness . on further questioning\nhe also volunteered that these symptoms had been preceded by a chronic cough , which had no obvious precipitant , and which had failed to resolve . on examination he had truncal ataxia , to the point where he had difficultly remaining upright when walking , and exhibited gaze - evoked first - degree nystagmus in his left eye on looking to the right .\nthe patient had suffered an episode of labyrinthitis 10 years earlier , and so he was prescribed pharmacological therapy aimed at a presumptive diagnosis of a second episode .\nsuccessive trials of prochlorperazine , betahistine , cyclizine and arlevert were not noted to have any positive effect on the patient 's dizziness and he was referred for outpatient neurological opinion . by the time of specialist review , the patient 's symptoms had worsened and he now described periods of severe nausea , with progression of his ataxia to the point where he was unable to stand unaided .\nhe had also developed an area of hypoesthesia on the left side of his face .\neye movements were adjudged to be markedly abnormal with dysmetric horizontal saccadic movements in addition to his ongoing nystagmus . his right vestibular ocular reflex was reduced and his left upper limb movements lacked coordination .\ngadolinium - enhanced magnetic resonance imaging ( mri ) of the brain revealed a homogenously enhancing , sharply demarcated 13 mm diameter lesion in the left posterior and lateral midbrain extending into the inferior cerebellar peduncle , with some adjacent oedema , suggestive of primary lymphoma ( see fig . 1 ) .\nstereotactic brain biopsy confirmed diffuse large b - cell lymphoma ( dlbcl ) and subsequent bone marrow biopsy and computer tomography ( ct ) imaging showed no evidence of lymphoma at any additional anatomical site . \n\nfigure 1:gadolinium - enhanced t1-weighted mri images ( panes lettered with coronal ( a ) , axial ( b ) and sagittal ( c ) sections ) showing a homogenous enhancement of a clearly demarcated lesion in the left posterior and lateral midbrain with extension into the inferior cerebellar peduncle . gadolinium - enhanced t1-weighted mri images ( panes lettered with coronal ( a ) , axial ( b ) and sagittal ( c ) sections ) showing a homogenous enhancement of a clearly demarcated lesion in the left posterior and lateral midbrain with extension into the inferior cerebellar peduncle .\nthe patient embarked on idaram ( idarubicin , cytarabine , methotrexate , dexamethasone ) chemotherapy followed by two rounds of high - dose methotrexate mono - therapy .\nimaging following treatment showed radiological remission and this is also seen on recent scans , now 2 years later ( see fig . 2 ) .\nwhile the symptoms of cerebellar dysfunction have largely abated since discharge , the patient has , however , been continually troubled by his cough . \n\nfigure 2:compares initial t1-weighted gadolinium - enhanced mri images ( seen in panes on left hand side : a , c and e ) with those taken following completion of treatment ( panes on right : b , d and f ) . radiological remission is shown in the post - treatment images .\ncompares initial t1-weighted gadolinium - enhanced mri images ( seen in panes on left hand side : a , c and e ) with those taken following completion of treatment ( panes on right : b , d and f ) . radiological remission is shown in the post - treatment images .\notolaryngology assessment , including symptom review , medication history , endoscopic evaluation and chest x - ray , was unable to elucidate any cause for cough other than the presumed effects of the medullary lesion .\nempirical trials of nasal steroids , nasal saline washes , high - dose proton pump inhibitor and inhaled bronchodilators were all unsuccessful .\ncoughing is a protective motor reflex under both voluntary and involuntary regulation , integrating physiological , psychological and social inputs .\nstudies in experimental animals have shown that vagal afferents signal peripheral sensory stimulation from the airways and lungs , and project centrally to the nucleus tractus solitarius ( nts ) with further projections between the nts and the medulla and pons . that such projections constitute a regulatory brainstem \ncough centre is a concept that has been extensively pursued ; attempting to determine the specific central pathways involved in the initiation and regulation of the efferent arc of the cough reflex .\nthe aetiology of chronic cough has been considered in a similar manner to the aetiology of chronic pain , with elements of both peripheral and central sensitization .\nmost of the common causes of chronic cough , and notably the classically described diagnostic triad of asthma , gastro - oesophageal reflux disease and postnasal drip , arise primarily through the activation of peripheral vagal afferents , but with probable central maladaptation contributing to hyper - sensitization to peripheral stimuli .\npathological impingement of the dorsal medullary region of the brainstem is recognized as a neurogenic cause of chronic cough in cases of patients with chiari i malformations and cough may be the initial symptom .\nhowever , to our knowledge , this is the first reported case of a lymphoma around the brainstem with chronic cough as one of the first symptoms .\nit is difficult to be certain as to the mechanism of chronic cough induced by this lymphoma .\nit may be that the expanding mass of the dlbcl compressed nearby nerve efferents serving the cough reflex , leading to aberrant hypersentization .\nhowever , dlbcl can be an aggressive lesion and has been reported to present with focal neurology from local invasion into nerves .\nit is possible , therefore , that the chronic cough in this case was caused by tumour infiltration into nerves rather than compression .\nalthough clearly cerebral lymphoma is a very rare cause of chronic cough , we believe that clinicians in primary and secondary care should consider rare central causes of chronic cough in cases where neurological symptoms or signs are present , or in cases where empirical treatment for the more common causes of cough fails to provide symptomatic relief .", "answer": "we report a rare case of chronic cough as the presenting symptom of a primary brainstem lesion . \n a 69-year - old gentleman presented with chronic cough followed by onset of progressive truncal ataxia , incoordination and nystagmus . \n contrast - enhanced imaging showed a midbrain lesion extending into the cerebellum , confirmed as lymphoma by stereotactic brain biopsy . \n the patient was successfully treated with chemotherapy , but his cough persists . \n we present this case to highlight the possibility of a brainstem lesion as a rare central cause of chronic cough , and suggest that the diagnosis is considered in those with concomitant neurological symptoms .", "id": 431} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nPlasma Levels of S100A4 in Portopulmonary Hypertension\n\nPaper sections:\nIntroduction\nExperimental models of pulmonary arterial hypertension (PAH) have implicated numerous genes in its pathogenesis. One such gene is S100A4, an intracellular calcium binding protein which causes pulmonary vascular remodeling in transgenic mice over-expressing the gene product (1). S100A4 also plays a role in tissue remodeling in lung and liver fibrogenesis (2,3) and metastatic tumor invasion (4).
PAH associated with portal hypertension, also known as portopulmonary hypertension (PPHTN), shares many pathological features with idiopathic and familial PAH (5). Approximately 5% of patients with cirrhosis being evaluated for liver transplantation have PPHTN (6\u20138), which may increase morbidity and mortality and greatly complicate liver transplantation (9,10).
There have been few studies of circulating biomarkers which characterize patients with PPHTN. We have previously shown that genetic variability in a S100A4 single nucleotide polymorphism (SNP) is associated with the risk of PPHTN in patients with liver disease (11). In the current study, we aimed to determine whether plasma levels of S100A4 were higher in patients with PPHTN compared to patients with advanced liver disease without evidence of PPHTN and disease-free controls.
\n\nStudy Design and Study Sample\nThe Pulmonary Vascular Complications of Liver Disease (PVCLD) study enrolled a cohort of 536 patients evaluated for liver transplantation or pulmonary hypertension at seven centers in the United States between 2003 and 2006. The only inclusion criterion was the presence of clinical portal hypertension with or without intrinsic liver disease. We excluded patients with evidence of active infection or recent (< two weeks) gastrointestinal bleeding, or who had undergone liver or lung transplantation. Full details of the cohort are published elsewhere (12).
We performed a case-control study within the PVCLD cohort. The study sample included newly-referred patients who were evaluated with transthoracic echocardiography (routinely performed for pre-transplant evaluation) during the study period. \"Prevalent\" patients who met the case definition (see below) were also included. We excluded patients with significant obstructive or restrictive lung disease, as previously defined (12). The study sample also excluded patients with human immunodeficiency virus infection (which may independently cause PAH), hepatocellular carcinoma or hepatic mass (which may affect S100A4 levels), or the presence of more than moderate aortic or mitral stenosis or regurgitation or significant left ventricular dysfunction by transthoracic echocardiography (which may result in pulmonary hypertension).
\n\nCase and Control Definitions\nCases with PPHTN met the following criteria at entry into the cohort: 1) mean pulmonary artery pressure > 25 mm Hg, pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) \u2264 15 mm Hg, and pulmonary vascular resistance > 240 dynes-s\u2022cm\u22125 measured by right heart catheterization, and 2) no other etiology for pulmonary hypertension. Controls met the following echocardiographic criteria at entry into the cohort: 1) right ventricular (RV) systolic pressure < 40 mm Hg (if estimable) and 2) absence of right atrial or ventricular dilation, hypertrophy, or dysfunction. \"Prevalent\" cases who had previously undergone evaluation and were subsequently being treated (n = 2) were also included; data from the initial evaluation (before treatment) were used for these cases. It was recommended that patients with RV systolic pressure > 50 mm Hg with abnormal RV morphology by echocardiography undergo right heart catheterization.
\n\nAssays\nPlasma was isolated from centrifuged whole blood and stored at \u221280\u00b0C. Plasma was then thawed and S100A4 concentration was assayed by enzyme linked immunosorbent assay (ELISA) (CircuLex, Nagano, Japan). All samples were assayed in duplicate according to manufacturer's instructions (13). Plates were read on a microplate reader and analyzed with SoftMax (Molecular Devices, Toronto, Canada) for quantification. Five samples had repeat analysis for estimation of the intraclass correlation coefficient (ICC) with 95% confidence interval (95% CI). Details of S100A4 genotyping are provided elsewhere (11).
\n\nData Analysis and Sample Size Calculation\nWe used Student's t-tests, Wilcoxon rank sum tests, chi-square tests, Fisher's exact tests, and Spearman's rho, as appropriate. Fourteen cases with 32 controls provided 80% power to detect a difference in plasma S100A4 levels of 0.9 standard deviations with a logistic non-parametric adjustment (\u03b1 = 0.05) (14).
\n\nResults\nFourteen cases with PPHTN and 32 controls with liver disease were assayed for plasma S100A4 level and genotyped. The baseline demographics of the patients are shown in Table 1. The mean \u00b1 SD age for both cases and controls was 52 \u00b1 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.03). There was no significant difference in the proportions of non-Hispanic whites between the two groups (p = 0.16). One patient with PPHTN was receiving bosentan and one patient was receiving intravenous epoprostenol; all other PPHTN cases were untreated at the time of assessment.
The median plasma S100A4 level was 83 ng/ml (IQR 25-271 ng/ml) for cases compared to 84 ng/ml (IQR 12-156 ng/ml) for controls (p = 0.58) (Figure 1A). Both groups had significantly higher S100A4 levels than healthy volunteers without liver disease (p < 0.05). These findings did not change significantly after adjustment for gender (Data not shown). Inter-assay reliability for plasma S100A4 was excellent (ICC = 0.99, 95%CI 0.98\u20131.0).
We then assessed the relationship of plasma S100A4 levels with genotype of the SNP rs743687 within the S100A4 locus. The median plasma S100A4 levels were 544 ng/ml in the one patient homozygous for the minor allele (CC), 147 ng/ml (IQR 19\u2013405 ng/ml) in the eight heterozygous patients (CG), and 74 ng/ml (IQR 18\u2013123 ng/ml) in the 53 patients without the minor allele (GG), consistent with a possible relationship between genotype and plasma S100A4 level (p = 0.11). (Figure 1B)
\n\nDiscussion\nThis is the first study to examine plasma S100A4 levels in patients with PPHTN and liver disease. While there was no significant difference in S100A4 levels between cases with PPHTN and liver disease controls, both groups had significantly higher levels than healthy controls without liver disease. We examined plasma level according to SNP genotype from S100A4 which suggested that the copy number of the minor allele might correlate with the plasma S100A4 levels.
The mechanism between S100A4 and PAH in animal models and humans is not clear. Merklinger et al showed that transgenic mice overexpressing S100A4 displayed increased thickness of the internal and external lamina of the pulmonary arteries (15). The elevation in RV systolic pressure seen in response to hypoxia failed to reverse with nitric oxide in the transgenic mice. The lungs of these mice showed upregulation of fibulin-5 and elastin expression, which are essential components of the extracellular matrix that contribute to vascular remodeling (16).
SNPs within the S100A4 locus have not been assessed in regards to their effect on the activity or expression of the gene product. We showed that the level of S100A4 might correlate with the SNP genotype associated with PPHTN, although concurrent processes such as hemolysis or inflammatory changes could also raise the plasma S100A4 levels S100A4 (17,18).
We assessed the value of plasma S100A4 as a biomarker of disease and found no significant differences between liver disease patients with or without PPHTN. However, the presence of liver disease itself likely led to increased plasma S100A4, which has been shown to be a robust marker of hepatic fibrosis (2). Indeed, it is possible that the elevated plasma S100A4 levels which characterize patients with advanced liver disease could serve as the milieu which permits other clinical, environmental, neurohormonal or genetic modifiers to trigger the occurrence of PAH in this setting.
There are limitations to our study. Despite having assembled a multicenter cohort of PPHTN patients, it remains a relatively rare disease leading to a small sample size. However, this study was adequately powered to detect a less than one standard deviation difference between the groups. It is possible that cases may have been misclassified as controls based on echocardiography without confirmatory right heart catheterization. To minimize this possibility, we set very stringent echocardiographic criteria for controls which essentially rule out PPHTN in patients with endstage liver disease.(19). We only examined the correlation of one SNP within the S100A4 locus with plasma levels. It may be important to define haplotypes which could have more substantial associations with the molecular phenotype.
In summary, there were no differences in plasma S100A4 levels between PPHTN patients and controls, which were greater than those of healthy controls. Our study showed that there might be a correlation between genotype variation and plasma S100A4 level. The presence of liver disease may nonspecifically increase plasma S100A4 or the high circulating levels of S100A4 in patients with advanced liver disease could facilitate the development of PPHTN.
\n\n\nS100A4 level according to disease status (A) and genotype (B). Genotypes include one patient homozygous for the minor allele (CC), patients heterozygous for the minor allele (CG), and patients without the minor allele (GG). Black bar represents median plasma concentration. White box represents interquartile range.
Demographics and liver disease variables
Data are shown as mean \u00b1 standard deviation or n (%). MELD = Model for End-stage Liver Disease
", "answer": "We previously showed that a single nucleotide polymorphism in S100A4 was associated with developing portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes-sec \\xc2\\xb7 cm\\xe2\\x88\\x925, and pulmonary capillary wedge pressure \\xe2\\x89\\xa415 mm Hg. Controls with liver disease had right ventricular systolic pressure < 40 mm Hg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 liver disease controls. The mean age for both cases and controls was 52 \\xc2\\xb1 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.02). There was no difference in S100A4 levels between cases and controls (p = 0.53). Both groups had significantly higher S100A4 levels than healthy volunteers (p < 0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.", "id": 432} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is caused by trauma , stress , sepsis , adrenal tumors , anticoagulation , hemorrhagic disorders and pregnancy .\nidiopathic adrenal hematoma. the symptoms vary from subclinical to clinical , such as nausea , abdominal pain , fever and hypotension due to circulatory collapse .\nadrenal tumors associated with hemorrhage primarily include pheochromocytomas , adrenocortical cancers and metastatic lesions from other organs . from a clinical perspective\n, whether the lesion is benign or malignant is an important issue but is difficult to determine prior to surgery .\na 59-year - old japanese man was referred to our hospital for evaluation of a 7.0 cm mass in the posterior segment of the liver or right adrenal gland in november 2009 .\nthis mass was discovered when abdominal ultrasonography was obtained to evaluate a weight loss of 8 kg from may to november 2009 .\nhis body temperature was 37.0c , his blood pressure was 124/73 mm hg , and his pulse was regular at 67/min .\nhormonal examination revealed a slightly elevated metanephrine level ( 0.35 mg / day ; normal range 0.040.19 ) .\ntumor marker levels , including serum -fetoprotein , carcinoembryonic antigen and carbohydrate antigen 19 - 9 were all within normal ranges . only pivka - ii was slightly elevated at 53 mau / ml ( normal < 37 ) .\nabdominal computed tomography ( ct ) demonstrated a well - demarcated , 7.0 cm lesion in either the posterior segment of the liver or in the right adrenal gland .\nthe peripheral region was slightly enhanced and the central part was hypovascular , indicating central necrosis ( fig .\nthere was no evidence of lymph node enlargement or distant metastasis . on magnetic resonance imaging ( mri ) ,\n, the mass showed arterial enhancement and a ct filling defect in the right superior and inferior adrenal arteries and arterial portography , respectively ( fig .\ni - meta - iodo - benzylguanidine ( mibg ) scintigraphy demonstrated no aberrant accumulation in the mass , which ruled out the possibility of a pheochromocytoma .\nfor the purposes of securing a definite diagnosis and treatment , an open right adrenalectomy was planned for march 2010 .\nthe resected specimen was 7.0 5.5 cm in size , and the cut surface of the mass was heterogeneous and dark red and white in appearance ( fig .\nhematoxylin - eosin staining revealed hemorrhage , necrosis and hemosiderin deposit with normal adrenal tissue .\nthe patient had an uneventful postoperative course and was discharged home on postoperative day 12 .\nsmall adrenal branches from the three main adrenal arteries form a subcapsular plexus , and the gland is drained by relatively few venules .\nfor example , stress increases adrenal vascularity and increases adrenal venous pressure due to vasoconstriction , resulting in intraglandular hemorrhage .\nidiopathic adrenal hematomas are difficult to diagnose prior to surgery . in japan , koizumi et al . described 14 cases of idiopathic adrenal hematomas from 1983 to 2010 .\nof these 14 cases , 13 had been suspected to be adrenal tumors including malignant lesions preoperatively , but were then found to be idiopathic adrenal hematomas on pathological examination after surgery . only 1 patient was diagnosed with an idiopathic adrenal hematoma without surgery .\nthe adrenal hemorrhage was not suspected to be caused by an adrenal tumor on the basis of ct , hormonal assay and mibg results , and this mass spontaneously regressed after 2 weeks .\nalthough imaging modalities such as ct and mri are helpful in detecting adrenal hemorrhage , it is difficult to determine whether the hemorrhage is associated with tumors or not .\nadrenal hemorrhage associated with pheochromocytoma ( 48% ) was the most frequently observed situation , and the second most frequently observed was a malignant lesion ( 20% ) such as adrenocortical cancer or metastasis from another organ .\nhematomas derived from pseudocysts or adenomas comprised 17% of all cases . therefore , even if pheochromocytoma is ruled out by hormonal evaluations and imaging studies , the possibility that the mass may be a malignant lesion remains approximately 50% .\nfurthermore , the size of adrenal incidentalomas , which are adrenal gland masses discovered serendipitously on imaging , is an important factor in differentiating benign tumors from malignant lesions .\nnieman recommended routine surgical resection for adrenal incidentalomas > 4 cm in diameter without a clear - cut diagnosis . in our case , metastatic liver tumors , hemorrhaged hepatic cellular carcinoma with central necrosis and adrenal tumor were raised as differential diagnoses at the time of the initial consultation because of ring enhancement with hypovascularity on enhanced ct and a slightly elevated pivka - ii level .\nsubsequently , abdominal angiography revealed the origin of the mass to be the right adrenal gland .\nalthough vital signs , laboratory data and mibg scintigraphy ruled out the possibility of a pheochromocytoma , the possibility of another malignancy could not be completely ruled out .\ntherefore , surgery was strongly recommended for a definite diagnosis as well as for treatment .\nthe reason for the patient 's weight loss and the increase in the pivka - ii in our case was not clear , but may have been related to exhaustion during the summer season from may until november that kept him from eating sufficiently .\nin fact , his weight loss ceased after he consulted our hospital , and the pivka - ii value also normalized prior to surgery . in conclusion , we report herein a case of idiopathic adrenal hematoma .\nan accurate diagnosis of idiopathic adrenal hemorrhage is quite difficult to make prior to surgery .\nsome imaging modalities are useful in generating a differential diagnosis , but if the potential for malignancy is not excluded , surgical resection should be taken into consideration .", "answer": "we report herein a case of idiopathic adrenal hematoma . \n a 59-year - old japanese man was referred to our hospital for evaluation of a 7.0 cm mass in the right upper abdominal cavity . \n the tumor was suspected to originate from either the posterior segment of the liver or the right adrenal gland . \n his chief complaint was weight loss of 8 kg over the previous 6 months . \n he had no past medical history and took no medications , including no anticoagulants . \n laboratory data were almost normal except for a slight elevation of pivka - ii . \n the origin of the tumor was found to be the adrenal gland , as angiography revealed the blood supply to the mass to derive from the right superior and inferior adrenal arteries . \n a fine needle biopsy of the lesion was unable to confirm the diagnosis . \n open right adrenalectomy was performed . \n the histopathological findings of the surgical specimen revealed a hematoma with normal adrenal tissue . in the absence of any obvious etiology , the diagnosis was idiopathic adrenal hematoma .", "id": 433} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndr . alexandre batista liver hemangiomas are the most common benign liver tumors . diffuse hepatic hemangiomatosis ( dhh ) is a rare disorder , usually occurring in the neonate , characterized by extensive replacement of liver parenchyma with hemangiomatous lesions .\nit is frequently associated with a palpable abdominal mass and high - output heart failure , with high mortality rate in neonates .\ndhh in the adult , especially without extra - hepatic involvement , is extremely rare .\nhemangiomatosis differs from multiple or giant hemangiomas in that the boundary of the lesion is ill - defined , while in the latter , the liver parenchyma surrounding the lesion is compressed by a fibrous capsule forming the wall of the hemangioma .\nan asymptomatic 68-year - old man was referred to our hospital due to the presence of numerous nodular hepatic lesions accidentally detected on ultrasound .\nthere was a history of heavy drinking ( alcohol intake around 70 - 90 g / d ) and no prior history of medication or steroid intake .\nphysical examination upon admission revealed diffuse hepatomegaly , with no associated cardiac murmur or leg edema .\nui / l ) . abdominal ultrasound ( us ) showed multiple ill - defined sub - centimeter hyperechoic hepatic nodules , predominately in the right lobe , with no posterior acoustic shadowing or significant through transmission and absence of high vascularity on color doppler [ figure 1 ] .\n68-year - old male referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .\na ) ultrasound examination demonstrates multiple ill - defined yperechoic nodules dispersed throughout the hepatic parenchyma , mostly sub - centimeter and with right hemi - liver predominance .\ncountless predominantly sub - centimeter nodular lesions with low t1-weighted signal intensity ( si ) and moderately high t2-weighted si were depicted .\nliver lesions showed moderately restricted diffusion , and post - contrast fat - suppressed t1-weighted images showed predominantly hypovascular features with retention of contrast in later phases .\na us - guided biopsy using an automated gun with an 18-gauge needle was performed collecting three representative fragments .\n68-year - old male referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .\na ) axial fatsaturated t2-weighted image shows countless small - sized moderately bright lesions ( arrows ) .\nb ) diffusion weighted image shows these lesions with high signal intensity ( b = 600 sec / mm ) ( arrows ) , which may be seen in liver hemangiomas secondary to t2 shine - through effect .\naxial c ) pre - contrast and ( d - f ) post - contrast fat - saturated t1-weighted images show arterial homogeneous enhancement ( arrows , d ) , some exhibiting portal phase peripheral nodular enhancement ( arrow , e ) and late centripetal filling ( arrows , f ) .\npathology revealed endothelial - lined sinusoidal proliferation with erythrocyte content , consistent with hepatic hemangiomatosis [ figure 3 ] .\ndefinitive diagnosis of dhh was established based on a combination of imaging and pathological findings and clinical / imaging follow - up .\ntwo years following the diagnosis , the patient 's hepatic function and imaging findings remain stable , with no relevant associated symptoms . 68-year - old\nmale referred to our hospital due to multifocal hepatic lesions , subsequently diagnosed as diffuse hepatic hemangiomatosis .\nultrasound guided biopsy samples stained with hematoxylin and eosin a ) 4 10 , b ) 40 10 ; c ) 40 10 ) .\nreveal numerous dilated nonanastomotic vascular spaces , which were lined by flat endothelial cells and supported by fibrous tissue endothelium .\nchronic inflammatory infiltrates with peri - portal distribution are also present ( black outlined asterisk , c ) .\nimaging plays a vital role in the detection and characterization of multifocal liver lesions in adults .\nthere are numerous causes including benign and malignant neoplasms , infectious lesions , and inflammatory conditions .\nthe us evaluation showed multiple sub - centimeter , ill - defined , hyperechoic nodules dispersed throughout the liver parenchyma , predominantly in the right hemi - liver , with very little or no flow seen on color doppler .\nthe differential diagnoses included metastatic disease , multifocal nodular fatty infiltration of the liver , bile duct hamartomas ( bh ) , or other less - frequent entities such as dhh or angiosarcoma .\nmetastatic liver involvement usually occurs in a patient with a known extra - hepatic primary neoplasm .\nsmall hypervascular liver metastases ( e.g. from breast or neuroendocrine tumors ) may mimic small early uniform enhancing hemangiomas ; however , these lesions tend to fade or wash out , whereas hemangiomas are more likely to maintain the si or fade toward background isointensity .\nalso , the majority of liver metastases shows heterogeneous or ring enhancement on the arterial phase images , confirming their definite diagnosis .\nmultifocal nodular fatty deposition is an unusual pattern of liver steatosis that consists of multiple round or oval fat foci randomly distributed throughout the liver .\nfat deposits appear isointense or hyperintense to the liver on in - phase images , dropping si on out - of - phase images .\nfat accumulation does not show restriction or shine - through effect on diffusion - weighted images .\nother clues indicative of multifocal fat deposition are the lack of mass effect , stability in size over time , and contrast enhancement similar to or less than that of the surrounding liver parenchyma .\nbh , also called von meyenburg complexes , originate from embryonic bile ducts that fail to involute . on ultrasound ,\nbh have been described as innumerable tiny hypoechoic or hyperechoic foci measuring less than 10 mm and distributed uniformly throughout the liver , with some displaying a comet tail artifact .\ndifferences in echogenicity may be due to the size of the dilated bile duct component , which , at a certain size , would behave like other microcystic structures . on mri\n, bile duct hamartomas usually appear as multiple tiny cystic lesions , strongly hyperintense on t2-weighted images .\nafter gadolinium administration , some authors described a thin rim of enhancement , which correlates with the compressed liver parenchyma surrounding the lesions . internal progression or retention\nit is very aggressive and sometimes may mimic hemangioma on dynamic studies , showing high si on t2-weighted images , since both tumors contain abundant blood - filled vascular spaces ; also , heterogeneous centripetal and progressive enhancement has been described .\ndhh is a rare , although benign , condition that is characterized by diffuse replacement of liver parenchyma by hemangiomatous lesions .\nthe natural history and prognosis of hepatic hemangiomatosis are poorly understood due to its rarity .\nhemangiomatosis is different from multiple or giant hemangiomas in that the boundary of the lesion is ill - defined , while in the latter , the liver parenchyma surrounding the lesion is compressed by a fibrous capsule that forms the wall of the hemangioma .\ndhh can occur in all age groups , but is most frequent in the neonate where it can result in high - output cardiac failure and significant mortality .\nit is usually asymptomatic in adulthood , being extremely rare when not associated with giant cavernous hemangiomas and even rarer when no other organ is affected besides the liver .\ntwo patterns of dhh are described , the diffuse ( non - nodular ) and the nodular pattern , the former being the predominant pattern , representing approximately two - thirds of the cases .\nsonographically , the liver affected by dhh appears as homogeneous hyperechoic areas with poorly defined margins ( diffuse pattern ) or a heterogeneous echo pattern with multiple discrete or coalescent small hyperechoic nodules ( multinodular pattern ) .\nthese nodular lesions are variable in size ( usually < 5 - 10 mm ) , appearing as countless oval or round hyperechoic nodular lesions . very little or no flow\n, the areas affected by hemangiomatosis may also display a diffuse non - nodular pattern composed of tiny cystic spaces separated by numerous thin hypointense septa , creating a lattice - like appearance or a diffuse nodular pattern consisting of multiple small discrete and coalescent nodules on t2-weighted imaging .\nthe extremely low velocity of blood flow within hemangioma relates to the absence of flow void seen in mri imaging .\ndynamic contrast - enhanced mri shows heterogeneous enhancement in these areas during the arterial phase that becomes more homogeneous during portal and delayed phase imaging .\nthe multinodular type , as was our case , exhibits small discrete and coalescent nodules with early homogeneous enhancement or the typical peripheral discontinuous enhancement during the arterial phase , showing uniform late retention of contrast .\nin conclusion , dhh with no associated cavernous hemangiomas and without extra - hepatic involvement is an extremely rare condition . despite its rarity\n, it can be suggested in adults presenting with multiple , predominantly sub - centimeter hepatic lesions demonstrating mri features of hemangiomas .\nmr imaging may be superior to us and computed tomography ( ct ) for the diagnosis and is the preferable cross - sectional imaging technique for long - term follow - up .", "answer": "we present a case of a pathologically proven multinodular diffuse hepatic hemangiomatosis ( dhh ) with no extra - hepatic involvement in a 68-year - old male . \n cavernous hemangioma is the most common hepatic tumor . \n however , dhh , which is characterized by extensive replacement of liver parenchyma with hemangiomatous lesions , has been rarely reported in adults . \n the etiology and clinical course are not completely understood because of its rareness , although the diagnosis might be suggested by the magnetic resonance imaging findings .", "id": 434} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndichlorvos ( dimethyl-2 , 2-dichloro vinyl phosphate ) is an organophosphorous ( op ) insecticide with moderate human toxicity , used for insect control in food storage areas , greenhouses , barns and control of insects on livestock .\nparenteral dichlorvos administration with suicidal intention is rarely reported in the literature . in one case report\n, extensive muscle necrosis was reported following intramuscular injection of dichlorvos . in another case , following injection of dichlorvos subcutaneously in both wrists , a young patient developed compartment syndrome requiring fasciotomy . in both cases\n, i describe the case of a young female patient , who developed atypical signs of op poisoning following subcutaneous injection of dichlorvos .\nthe present case report is about a 37-year - old , previously healthy female , who was admitted to our intensive care unit 18-h after alleged self - injection of 76% dichlorvos ( nuvos ) 3 ml in the upper left arm ( 3 times with a 1 ml insulin syringe ) . within an hour of the injections\n, she had normal body temperature with heart rate of 90/min , blood pressure 110/70 mmhg , respiratory rate 14/min and pulse oximeter showing 100% saturation on room air .\nno crackles were heard on chest auscultation . on the nervous system examination , she was jittery with slurred speech and normal cranial nerves .\nshe had hypertonia , brisk tendon reflexes , bilateral sustained ankle clonus and bilateral extensor plantar reflex .\nlocal examination revealed a blister and a black necrotizing lesion over the anterior aspect of the left arm [ figure 1 ] .\nshe was rapidly atropinized with incremental boluses of atropine ( total dose 12 mg ) in next 30 min ( targeting a dry mouth ) followed by infusion of 1.8 mg / h .\npralidoxime infusion was started at 500 mg / h following a loading dose of 1000 mg over 20 min .\nintravenous clindamycin ( 600 mg q 8 h ) was administered empirically for presumed local wound infection .\ndebridement of the wound showed predominant involvement of the subcutaneous tissue plane with minimal necrosis of the superficial fibers of biceps brachii .\ninitial routine laboratory investigations were unremarkable except elevated total count ( 16200/mm ) and mild respiratory alkalosis .\nlocal skin necrosis with surrounding blisters her clinical course was complicated by respiratory arrest 9-h after hospital admission ( 27-h after the injection of dichlorovos ) leading to hypoxia and bradycardia .\narterial blood gas analysis post resuscitation showed - ph 7.28 , po2 - 36 mmhg , pco2 - 54 mmhg , hco3 - 22 mmhg .\nserum choline esterase ( pseudo cholinesterase ) level of the same day showed a very low value of < 1 ku /\nshe could be successfully weaned off from the ventilator on day 4 . on day 5 , while on atropine infusion she was found to be delirious .\nshe was also noticed to have extrapyramidal manifestations including rigidity and left sided gaze preference .\nin this case , other than the unusual route of administration , a number of atypical manifestations were found .\nthis includes relatively delayed respiratory failure and central nervous system ( cns ) manifestations with few muscarinic signs .\ntwo independent mechanisms are thought to be responsible for respiratory failure following op insecticide poisoning cholinergic cns depression in the early stage ( associated with other cholinergic features ) and late progressive neuromuscular transmission defect .\nsecond mechanism is part of the syndrome described as type ii paralysis by wadia et al . or intermediate syndrome by senanayake and karalliedde . our patient developed respiratory arrest 27-h after exposure to dichlorovos .\nin her clinical course she never had neck or proximal muscle weakness , though the clinical findings were not correlated electrophysiologically .\nusually cns signs are manifested early in the course in the presence of peripheral muscarinic signs . in a large series published on neurological manifestations of op compounds , 8 of 200 patients had pyramidal tract signs in the form of only hyper - reflexia manifesting within 24 h of exposure .\nall these patients were unconscious with florid cholinergic manifestations , including constricted pupils . in their original series of intermediate syndrome senanayake and karalliedde , observed hyperreflexia in one of their patients ( with flexor plantar reflex ) and even she had typical muscarinic signs .\nextrapyramidal signs of op poisoning are often transient and may be missed in a sick patient . in a taiwanese series\ncns manifestations ( both pyramidal tract and extrapyramidal ) were delayed and were associated with relatively scanty peripheral muscarinic signs .\npossible explanation for these atypical manifestations in our patient could be route specific ( in this case subcutaneous ) effect of op compound ( dichlorovos ) causing isolated delayed cns depression , with few peripheral cholinergic signs .\nanimal experiments have shown route specific ( subcutaneous or intravenous ) cardiovascular and neuromuscular effect of op compounds in rats .", "answer": "current case report describes a 37-year - old female patient who was admitted to the hospital following subcutaneous injection of dichlorvos with an insulin syringe . \n the only peripheral cholinergic sign observed on admission was excessive salivation with bilateral pyramidal tract signs . \n locally she had necrosis of skin and subcutaneous tissue with surrounding blisters . \n in the subsequent course of her illness , she developed respiratory arrest requiring ventilator support . \n she also had delayed extrapyramidal manifestations . \n relevant literature is reviewed . \n possibility of route - specific , delayed predominant central nervous system effect of dichlorvos postulated .", "id": 435} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nforty - five - year - old male shelter resident , chronic alcoholic , chronic smoker , and marijuana abuser presented to emergency department ( ed ) with complaints of intermittent fever with night sweats and productive - cough for 10 days with yellowish sputum associated with pleuritic chest pain .\nhe complained of generalized weakness and decreased appetite and claimed to have lost approximately 10 pounds in 2 weeks .\nlaboratory results showed leukocytosis of 17,000/mm with neutrophil differential of 11,200/mm ( 65% ) with band neutrophils of 10% .\nchest radiograph was reported as right middle lobe consolidation but careful observation revealed a foreign body ( fb ) , likely a tooth in the right bronchus intermedius ( fig .\nct scan of chest showed a well calcified fb likely a tooth at the level of carina obstructing right intermedius bronchus and consolidation in right lower lobe indicating post - obstructive pneumonia ( fig .\n2 ) . patient was admitted and prescribed intravenous antibiotics targeting gram - negative organisms and anaerobes .\ndeep conscious sedation was achieved by propofol infusion in the presence of an anesthesiologist and cardiothoracic surgery backup .\nbronchoscopy showed tooth in right intermediate bronchus with ~75% occlusion , and purulent secretions from the right main stem ( figs .\nthe fb was removed successfully with rat tooth forceps ( figs . 7 and 8) .\npost bronchoscopy inspection showed right main stem , bronchus intermedius , and right middle and lower lobe bronchi to be well patent .\ncloser view of the foreign body , identifiable as tooth in right main stem bronchus .\nthe aspirated tooth removed by rat tooth forceps . upon further questioning , the patient said that he did not remember having aspirated the tooth and hence the duration of aspiration could not be known .\nhe was discharged home on oral antibiotics a couple of days after the bronchoscopy and counseled to quit alcohol and drugs .\nfba is more common in children than adults with about 80% occurring in children aged less than 15 years .\nit is the fourth most common cause of unintentional injury deaths in the united states . while choking is a hazard for all ages , choking deaths peaked at age 84 in 2011 as per national safety council injury facts 2015 ( 1 ) .\nfba in adults is often overlooked as a potential cause of airway obstruction especially if there is no asphyxiation .\nadults with risk factors such as alcoholism , drug abuse , mental retardation , and neuromuscular conditions are predisposed to aspiration .\nhowever , accidental aspiration in adults without the aforementioned risk factors has been described ( 25 ) . in adults ,\nmost common foreign bodies aspirated are food and broken fragments of teeth ( 68 ) .\nct scan is more sensitive and specific than chest radiograph in diagnosing radiolucent foreign bodies and for characterizing the attenuation of a suspected fb ( 9 ) .\nunlike in children , less than half of fbs are lodged in the proximal airways in adults .\nmost of the fbs are lodged in the right bronchial tree , whereas in children no significant difference was seen between right and left bronchial tree ( 6 ) .\nbronchoscopy for the removal of fb was introduced by gustav killian , an otolaryngologist in 1897 .\nanimal studies performed by zavala and rhodes ( 11 ) showed that fbr could be used to retrieve different kinds of fbs by using grasping forceps through the bronchoscope .\nfbr is considered as the diagnostic test of choice for initial diagnosis of fb in adults .\nthe advantages of fbr over rigid bronchoscopy are that it can be performed under local anesthesia , visualization of smaller peripheral airway is better with relatively easier manipulation , and can be performed in patients with deformities of c - spine and pharynx .\nit is also a relatively easy and safer procedure in experienced - hands ( 10 , 12 ) .\nrigid bronchoscopy is recommended if fbr fails , if the fb is centrally located , if firmly embedded in scar tissue , and for removal of sharp objects which require maneuvering to minimize mucosal trauma ( 13 ) .\nthere have been several case series which have reported successful removal of foreign bodies by fbr .\ncunanan ( 12 ) reported a success rate of 89% in using fbr for the removal of fb in 300 mentally retarded and physically handicapped patients .\nthey reported a decrease in mortality from 12 to 1% with the use of fbr over rigid bronchoscope .\nthey , however , attribute to the increased mortality from rigid bronchoscopy to complications of general anesthesia in patients with comorbidities .\nlimper and prakash had a success rate of 60% with fbr , whereas rigid bronchoscopy showed a success rate of 98% . in their experience , fbr is advantageous in distally lodged fb , in cases with cervical instability , mechanically ventilated patients , and also in removal of small fbs , which can be securely grasped with a fiberoptic bronchoscope ( 14 ) .\n( 15 ) report a success rate of 97% for fb removal via fbr with low mortality and morbidity .\nthey also reported that granulation tissue can be removed without much bleeding ; thus , removal of fb can be achieved in a repeat fbr a week later .\n( 13 ) indicate that fbr can be used to remove foreign bodies especially if they are small and peripheral and that fbr may be superior to rigid bronchoscopy for grasping tiny and far - reaching foreign bodies .\nrigid bronchoscopy is recommended if fbr fails and especially if the fb is large and located in central bronchi or trachea .\nhowever , in children who may have central , asphyxiating foreign bodies , the rigid bronchoscope under general anesthesia is preferentially indicated .\nteam - based approach with designated roles for team members improves the chances of a successful procedure .\nanesthesia and ct surgery backup is essential . team - based analysis of the nature , location of the fb , and appropriate accessory instruments is equally necessary .\nsteroids can be given to minimize inflammatory changes as they may lead to difficulty in fb extraction .\norotracheal approach is preferred over nasotracheal , as it avoids fb from being lost in the nasal passages if accidently dislodged .\ncare should be taken to keep fb in the center of visual field and to avoid pushing fb distally into the airways .\nonce fb has been secured , bronchoscope , accessory instrument , and the secured fb are all withdrawn from the airway simultaneously .\nrare complications of fbr are likelihood of asphyxiation from losing the fb in the subglottic area and hemoptysis ( 10 ) .\nanother approach is to reinsert flexible bronchoscope to push the fb into more peripheral airway thus resolving the central airway obstruction . in case of hemoptysis ,\nairway can be better managed by rigid bronchoscope , but this complication is very rare if performed by trained operators .\nincidence of massive hemoptysis even in patients with significant granulation tissue around the fb is extremely low ( 15 ) .\norganic materials can cause severe inflammation in a short period of time and tend to absorb water with development of airway obstruction relatively earlier .\nin contrast , inorganic fbs are inert , and so patients might be asymptomatic for a prolonged period ( 16 ) . grasping forceps , baskets , magnet extractors ,\nyag laser , and cryoprobes are available as accessories for fb removal via flexible bronchoscope ( 10 ) .\nrat tooth forceps is a type of a grasping forceps , which is particularly useful for removing hard , flat , or thin organic or inorganic foreign bodies .\nthese are used primarily when the fb is hard as a firm grip can be achieved .\nthese can not be used for the retrieval of organic friable objects which tend to fracture due to the firmness of the grip provided by these forceps ( 10 ) .\nzero - tip basket is used in urological procedures like retrieval of ureteral stones . the tipless design allows close approximation to fb .\nthey are used to retrieve fbs lodged in distal bronchi and mobile fbs ( 16 , 17 ) .\nfish net basket , a modified polypectomy snare , is useful in removing bulky fbs ( 10 ) .\nmagnet extractors contain flexible probe tipped with a magnet , useful for retrieval of metallic fbs ( 10 ) .\nfbs embedded in granulation tissue can be removed by yag laser , which vaporizes the surrounding granulation tissue .\ncryoprobe is used to freeze friable organic and small inorganic materials . freezing the foreign bodies\nhigh index of suspicion is needed especially for high - risk patients presenting with compatible symptoms .\nfbr is the initial diagnostic and therapeutic procedure recommended with low complication rates in experienced hands .\nrigid bronchoscopy is performed if the flexible bronchoscopy fails or if the fb is large and centrally located , in case of significant hemoptysis and if significant granulation tissue is present with a fb which is deeply embedded .", "answer": "foreign body aspiration ( fba ) is more common in children than adults with about 80% occurring in children aged less than 15 years . \n fba in adults is often overlooked as a potential cause of airway obstruction especially if there is no asphyxiation . \n we present a case of a 45-year - old male with alcohol abuse who presented with post - obstructive pneumonia secondary to aspiration of tooth of unknown duration . \n the tooth was removed via flexible bronchoscopy ( fbr ) and we will discuss the use of fbr for foreign body ( fb ) removal , which fb can be easily removed by fbr , and the different techniques and devices used for fb removal via fbr .", "id": 436} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSensitive Cu2+-Cu2+ Distance Measurements in a Protein-DNA Complex by Double-Quantum Coherence ESR\n\nPaper sections:\nIntroduction\nHerein, we demonstrate a simple way to measure paramagnetic metal ion based nanoscale distances in proteins. The advent of Double Electron Electron Resonance (DEER)1,2 and Double Quantum Coherence (DQC)3,4 methods that measure nanometer range interspin distances have had a profound impact on the application of ESR in biological research.5\u201312 Most of these distance measurements are based on the methanethiolsulfonate nitroxide spin-label, which is chemically attached to the cysteine residue in proteins.13 The extension of DEER and DQC distance measurements to paramagnetic metal ions can potentially generalize the technique to many proteins that contain endogenous metal ion binding sites. However, DEER and DQC with metal ions as spin probe are challenging because of large ESR spectral width and low signal to noise ratio (SNR). Nevertheless, our group14,15 and others16\u201326 have made tangible progress. In principle DQC can have a high SNR per shot. This provides impetus for further research of DQC. On the other hand, the DQC signal has substantial contributions from electron-nuclear interactions between the electron spin and neighboring 14N as well as 1H nuclear spins that are present in the amino-acid coordination environment. These nuclear modulation27 effects swamp the modulation due to the electron-electron dipolar (EED) interactions and make it difficult to measure the interspin distance.
EcoRI is a 62 kDa homodimeric protein28,29 that recognizes and binds to the 5'-GAATTC-3'DNA sequence with high specificity30\u201332, even in the absence of metal cofactors. In the presence of Mg2+, EcoRI catalyzes cleavage of both DNA strands at this site. When Mg2+ is replaced by other metal ions the cleavage rates decrease according to the series Mg2+ \u2248 Mn2+ > Co2+>> Zn2+ >> Cd2+ > Ni2+.31 Interestingly, Cu2+ is a powerful inhibitor of EcoRI catalysis.33 In order to shed light on the molecular mechanism of catalytic inhibition by Cu2+, we have recently exploited DEER based distance measurements to determine that Cu2+ binds to His114 in each subunit of EcoRI,33 at points 13 \u00c5 from the Mg2+ positions in the catalytic sites. The positions of the His114 sidechains are consequently altered, and the resulting disruption of critical protein-DNA interactions and water molecules in the catalytic centers leads to inhibition of catalysis.33
In this work we present a simple way to minimize the low frequency nuclear peaks in the DQC spectrum and resolve the dipolar interaction between two paramagnetic probes Cu2+ with high sensitivity in the complex of restriction endonuclease EcoRI with its cognate DNA.
\n\nEnzyme expression and purification\nThe EcoRI protein was expressed from a maltose-binding protein-EcoRI (MBP-EcoRI) fusion construct. Details for generation of the fusion gene and expression of the fusion protein are given in supporting information for reference 33. The complete EcoRI protein without extra amino acids was isolated, purified, and characterized as described in reference 34.
\n\nCu2+-EcoRI-DNA sample preparation\nA solution of EcoRI (5 \u03bcM) in the presence of fivefold molar excess of TCGCGAATTCGCG was exchanged into 30 mM N-ethylmorpholine (NEM) buffer, which contains 0.3 M NH4Cl, 10% dioxane, 30% deuterated glycerol (d8), 65% D2O (pH 8.0) and concentrated. The final concentrations of EcoRI and DNA were 380 \u03bcM and 1.5 mM, respectively. Isotopically enriched 63CuCl2 (Cambridge Isotope Labs, Inc) was added at a 4:1 molar ratio (Cu2+ : protein dimer). The sample was stored at \u221280\u00b0C and flash-frozen before each ESR experiment.
\n\nElectron Spin Resonance Spectroscopy\nAll of the pulsed ESR experiments were performed on a Bruker Elexsys 580 spectrometer at 20 K, with a MD5 resonator. The six pulse DQC-ESR was using a \u03c0/2-tp+dt-\u03c0-tp+dt-\u03c0/2-t1-\u03c0-t1-\u03c0/2-t2-\u03c0-echo sequence. A 64 step phase cycle was carried out to select the correct coherence pathway and the DQC-echo after the sixth pulse was integrated.14,35 The \u03c0/2 pulse and \u03c0 pulse lengths were 8 ns (or 12 ns, 16 ns and 20 ns) and 16 ns (or 24 ns, 32 ns and 40 ns), respectively. The interval tp was incremented from 80 ns with a stepsize of 8 ns, for a total of 360 points. The interval t1 was 80 ns and t2 was 200 ns. The shot repetition time was 5 ms and all the DQC time domain data were averaged for 24 scans. Each DQC experiment was done at 3350 G where the maximum echo signal was observed. Details of the DEER experiment are given in supporting information and reference 33.
\n\nResults and Discussion\nFigure 1 shows the Cu2+-DQC data obtained at the g\u22a5 position of the Cu2+ ESR absorption spectrum. The lengths of the \u03c0 pulse were 16 ns (black solid line) and 40 ns (grey solid line), respectively.
The two spectra in Figure 1b with different length of \u03c0 pulse clearly contain peaks that can be attributed to the 14N-nuclear modulations in the 0\u20135 MHz region14 as well as the 1H-nuclear peaks at ~14 MHz. For the purpose of nanoscale distance measurements the 0\u20135 MHz 14N-nuclear peaks are particularly problematic, since the EED interaction is in this region. Interestingly, the intensity of the peak at ~1.46 MHz in the DQC spectrum (Figure 1b) with 40 ns \u03c0 pulse is much lower compared to the spectrum with 16 ns \u03c0 pulse. With shorter \u03c0 pulse, e. g., 16 ns, the spectral excitation probability of the DQC EED interaction is about 0.16.35 With the longer \u03c0 pulse of 40 ns, the spectral excitation probability of the DQC EED interaction is about 0.04.35 It is very clear that longer \u03c0 pulse cannot substantially populate the double quantum coherence of EED interaction. However, the nuclear hyperfine and quadrupole transitions are weakly sensitive to the length of \u03c0 pulse.27 This suggests that 1.46 MHz peak might originate from the Cu2+-EED interaction.
Since the experimental DQC signal is a multiplication of the EED and the nuclear signals, division of the \u03c0=16 ns DQC data by the \u03c0=40 ns DQC data may suppress the nuclear signals and resolve the EED signal.14,35\nFigure 2a shows the comparison of the DQC time domain data, after dividing the \u03c0=16 ns signal by the \u03c0=40 ns signal (black solid line), with the DEER data after subtraction of the homogeneous background (grey solid line).33 The modulation periods of the two time domain traces are comparable. In this analysis, the DQC signal with 40 ns \u03c0 pulse was empirically chosen for division \u2013 the data with other choices are shown in the Supporting Information. The data acquisition time of DQC (including two traces) and DEER are ~50 hrs and ~43 hrs, respectively. The data collection time in DQC can be reduced by implementation of on-board phase cycling.
The DQC spectrum after division, shown in Figure 2b (black solid line), clearly resolves the major peak at ~1.46 MHz, which is consistent with the DEER data (Figure 2b, grey solid line). Nevertheless, the DQC spectrum is narrower than the DEER spectrum. In the experimental DQC data, there might be some small residual peaks from electron-14N interactions that occur at ~3 MHz.
Figure 2 also shows the simulated DQC data (black dotted line). Based on the best fitting of the DQC time domain data shown in Figure 2, we obtained a most probable Cu2+-Cu2+ distance of ~35 \u00c5 with a standard deviation of 1 \u00c5 (Figure 2b, black solid line inset). This result is consistent with our observation from DEER experiments (Figure 2b, red dotted line inset). The simulated DQC spectrum is in accord with the dominant peak obtained in the experiment, although the DQC data is narrower.33 Details of the simulations are provided in the Supporting Information. It is likely that in DQC a narrower range of orientations is selected because the microwave pulses have a finite coverage. Despite this, the signal to noise ratio per shot in DQC is high (cf. figure caption in Figure 2 and Supporting Information).
\n\nConclusions\nWe have clearly shown here that metal ion based nanometer range distance can be measured by DQC. DEER has a significant advantage due to the ease of implementation on commercial instrument. Nevertheless, the DQC data have high SNR per shot. Further improvements can be made by the use of narrower pulse lengths35 and by understanding the role of orientational effects in such DQC measurements.15,36
", "answer": "Double Quantum Coherence (DQC) ESR spectroscopy is applied to measure the Cu2+-Cu2+ distance in the EcoRI-DNA complex. A simple method is proposed to reduce the contribution of nuclear hyperfine and quadrupole interactions to such data. The effects of such interactions between the electron spin of Cu2+ and neighboring nuclei on the DQC data, make it difficult to measure the nanometer range interspin distance. The DQC data is in good agreement with results obtained by Double Electron Electron Resonance (DEER) spectroscopy. At the same time, the signal to noise ratio per shot in DQC is high. Taken together, these results provide impetus for further development of paramagnetic metal ion-based DQC techniques.", "id": 437} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n focal epilepsies account for about two - thirds of all adult epilepsy patients , and temporal lobe epilepsy ( tle ) is the most common type of focal epilepsy ( 1,2 ) .\ntemporal lobe epilepsy is subcategorized as mesial ( i.e. , amygdalohippocampal ) and neocortical ( i.e. , lateral ) temporal .\nmesial temporal lobe epilepsy ( mtle ) with hippocampal sclerosis ( hs ) is one of the most common types of epilepsy referred for surgical treatment ; it is often refractory to antiepileptic drugs ( aeds ) , but responds favorably to surgery ( 1,4 ) .\npatients with mtle - hs and intractable seizures often experience progressive behavioral changes including increasing memory deficit with the passage of time .\nin addition , surgical outcome may be worse with longer duration of epilepsy or increasing age at surgery , which suggests that mtle - hs is a progressive disorder ( 5 ) .\ntherefore , early detection of this syndrome and its distinction from other tle syndromes has important practical implications with regard to planning an optimal treatment strategy for the affected patient . \n \n in the current study\n, we tried to compare the clinical characteristics of patients with mtle - hs with those who had tle due to other etiologies in order to identify potentially differentiating clinical characteristics between these two groups of patients . \n\n\n in this retrospective analytic study all patients with a clinical diagnosis of tle were recruited in an outpatient epilepsy clinic at shiraz university of medical sciences , which is the only referral epilepsy clinic in south iran .\nthe diagnosis of tle was made exclusively by one epileptologist working at this institution ( the first author ) and based on clinical grounds ( semiology ) , electroencephalographic ( eeg ) findings and imaging , such as magnetic resonance imaging ( mri ) .\nall patients were followed up by the epileptologist at our institution for at least one year ( i.e. , until may 2014 ) .\nroutine eeg was requested for all patients at the time of referral . in difficult - to - diagnose or\ndifficult - to- treat patients we often order video - eeg monitoring to ascertain the diagnosis and formulate an individualized treatment plan , accordingly .\nfor all patients , a 1.5 tesla brain mri ( epilepsy protocol ) was performed . \n \n\nwe classified patients as having mts ( if they had clear signs of mesial temporal sclerosis and/or atrophy in their mri ) and those who had any other mri abnormality .\npatients with dual pathology ( i.e. , mesial temporal sclerosis associated with other structural lesions ) were excluded from the study . \n \n\nage , gender , age at seizure onset ( i.e. , the first afebrile seizure ) , seizure type(s ) , epilepsy risk factors ( including pregnancy complications , history of febrile seizure , cns infection , significant head trauma , positive family history of epilepsy ) , eeg findings ( the most informative eeg ) , and mri findings of all patients were registered routinely .\nseizure types were categorized as generalized tonic clonic seizures ( gtcs ) , complex partial seizures ( cps ) and auras .\npearson chi - square , fisher 's exact , and mann - whitney u tests were used for statistical analyses .\n\n until may 2014 , 2890 patients with epilepsy were registered at our epilepsy clinic .\nfour hundred twenty - seven patients ( 14.7% ) were diagnosed as having tle . of these ,\n174 patients were eligible to enter the study ( 105 patients with mtle - hs and 69 patients with tle due to other etiologies ) .\ndemographic and clinical characteristics of patients with mtle - hs and those who had tle due to other etiologies are shown and compared in table 1 .\nfrequency of seizure types ( i.e. , gtcs vs. cps vs. auras ) was not significantly different between these two groups ( table 1 ) .\nspecific types of auras were significantly different between these two groups ( table 1 ) , however most auras were reported by both groups , similarly .\nepilepsy risk factors were reported to be as follows ( mtle - hs vs. others ) : parental consanguinity in 41 / 30 ( p= 0.6 ) , family history of epilepsy in 18 / 10 ( p= 0.6 ) , significant head trauma in 15 / 7 ( p= 0.4 ) , cns infection in 2 / 2 ( p= 0.6 ) and pregnancy complications in 2 / 3 ( p= 0.3 ) . \n \n\nmtle - hs : mesial temporal lobe epilepsy ( mtle ) with hippocampal sclerosis ( hs ) . \n \n\nvideo - eeg monitoring was available in 155 patients ; and 19 patients had a routine eeg only .\neleven patients ( 10.4% ) with mtle - hs and four ( 5.8% ) with other etiologies had normal eeg ( p= 0.2 ) .\nright sided , left sided or bilateral focal epileptiform discharges ( i.e. , temporal seizures , spikes or sharp waves ) were observed in 36 , 38 , and 20 patients with mtle - hs and 31 , 21 and 13 patients with other etiologies , respectively ( p= 0.4 ) . focal polymorphic delta activity or temporal intermittent rhythmic delta activity ( tirda ) was seen in 60 and 7 patients with mtle - hs , respectively .\nthese figures were 32 and 4 in patients with other etiologies ( p= 0.3 ) . \n \n\nmagnetic resonance imaging ( mri ) in patients with other etiologies ( non- mtle - hs group ) showed temporal lobe tumors in 27 patients ( 39.1% ) , non - specific white matter mri abnormalities in 11 ( 15.9% ) , cavernoma in seven ( 10.1% ) , sequels of head injury in six ( 8.7% ) , arachnoid cysts in five ( 7.2% ) and other etiologies in 13 ( 18.8% ) patients .\ntwelve patients had dual pathology ( mesial temporal sclerosis in addition to another lesion ) .\n\n mesial temporal lobe epilepsy with hippocampal sclerosis is a common type of epilepsy referred for surgical treatment due to medical refractoriness . as a matter of fact\nhowever , it has been suggested that early surgical intervention after seizure onset is an important precondition for achieving seizure - free status after surgery ( 6 ) .\ntherefore , early detection of this syndrome has important practical implications with regard to planning an optimal treatment strategy for the affected patient , particularly those with medically - refractory seizures . \n \n in the current study\n, we observed that earlier age at epilepsy onset ( i.e. , teenagers compared to young adulthood ) , a past history of febrile seizures and reporting affective auras ( e.g. , fear , anxiety , depression , joy , and anger ) were commonly seen in patients with mtle - hs , while auditory auras were more frequently reported by those with tle due to other etiologies .\nin previous studies dominantly represented by patients with hs on mri , it has been observed that age at onset is variable ( 7 ) .\nthe finding that age at onset is a potential clinical variable to distinguish mtle - hs from tle due to other etiologies should be further explored in future studies . \n \n\nseveral studies have shown a significant relationship between a history of febrile seizures in early childhood and mesial temporal sclerosis . in one study , it was observed that hippocampal t2 hyperintensity after febrile status epilepticus represents acute injury often evolving to a radiological appearance of hs after one year ( 8) . having a past history of febrile seizure is a useful historical clue in favor of mtle - hs compared to tle due to other etiologies . \n \n as the first ictal symptoms\n, auras can provide important localizing and lateralizing information useful in determining the location of the epileptogenic zone ( 9 ) .\nthe observation that , affective auras ( e.g. , fear , anxiety , depression , joy , and anger ) were commonly seen in patients with mtle - hs , while auditory auras were more frequent among those with tle due to other etiologies , has very important clinical implications . in one study ,\nthe authors examined the relationship between presence of different types of auras and post - surgical outcomes in 157 patients with medically intractable mesial temporal lobe epilepsy ( mtle ) with unilateral hippocampal sclerosis ( hs ) .\nthe occurrence of multiple auras was not associated with post - surgical outcome ( p = 0.7 ) .\nbut , the presence of extratemporal auras ( e.g. , somatosensory , visual and dysphasic auras ) was significantly higher in patients with poor outcome ( 10 ) . designing future studies to investigate the relationship between presence of mesial temporal lobe auras ( e.g. , psychic symptoms , cognitive and affective auras , autonomic auras such as epigastric sensation , olfactory and gustatory auras ) versus lateral temporal lobe auras ( e.g. , vertiginous and auditory auras ) and surgery outcome in patients with mtle - hs is necessary . \n\n\n the mainstay for making a correct diagnosis , when evaluating a patient with seizure , is having a standardized approach , particularly with regard to taking a detailed clinical history .\none may find important clues in the clinical history ( e.g. , age at onset , detailed seizure description and past history ) to make a syndromic diagnosis .\nthe syndromic diagnosis forms the basis for the treating physician to decide upon an appropriate management plan . \n\n\n this was a clinic - based series and may not represent the full spectrum of tles . \n\n\n we would like to thank neurosciences research center , shiraz university of medical sciences , shiraz , iran for supporting this study .", "answer": "background : this study compares the clinical characteristics of patients with mesial temporal lobe \n epilepsy with hippocampal sclerosis ( mtle - hs ) with those who have temporal lobe epilepsy ( tle ) \n due to other etiologies \n . \n\n methods : in this retrospective study all patients with a clinical diagnosis of tle were recruited in a \n referral outpatient epilepsy clinic at shiraz university of medical sciences from september 2008 to \n may 2013 . \n we classified the patients with tle as having mesial temporal sclerosis if they had clear \n signs of mesial temporal sclerosis and/or atrophy in their mri and others who had any other mri \n abnormality . \n\n \n results : a total of 174 patients were studied ( including 105 patients with mtle - hs and 69 patients \n with tle due to other etiologies ) . \n frequency of seizure types was not significantly different \n between these two groups . \n earlier age at epilepsy onset ( p= 0.005 ) , a past history of febrile seizures \n ( p= 0.010 ) and presence of affective auras ( p= 0.008 ) were commonly seen in patients with mtlehs , \n while auditory auras ( p= 0.020 ) were more frequent in those with tle due to other etiologies . \n\n \n conclusion : the mainstay for making a correct diagnosis , when evaluating a patient with seizure , \n is having a standardized approach , particularly with regard to taking a detailed clinical history . \n one \n may find important clues in the clinical history ( e.g. , age at disease onset , detailed seizure description \n and past history ) to make a correct diagnosis .", "id": 438} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npulmonary sequestration ( ps ) is a rare developmental disorder characterized by the presence of a nonfunctioning lung parenchyma that lacks normal tracheobronchial tree connection and is supplied by a systemic artery.1 \n congenital diaphragmatic hernia ( cdh ) is a malformation characterized by a diaphragmatic defect through which the abdominal viscera migrate into the chest during fetal life.2 \n the association between ps and cdh has been previously described.1 \n 2 \n 3 \n 4 \n 5 \n 6 \n 7 we report the case of a neonate affected by prenatally diagnosed cdh treated by thoracoscopy . during the procedure\n, we detected an associated extralobar ps , which was preoperatively undiagnosed , and removed it .\na female infant was delivered by elective cesarean section at 35 weeks of gestation and was referred to our department for prenatal diagnosis of left diaphragmatic hernia detected at 32 weeks of gestation by ultrasounds and characterized by a lung - to - head ratio ( lhr ) of 1.6 .\nweight at birth was 3,400 g , and apgar index was 9 at 1 minute and 10 at 5 minutes , respectively . at birth , the newborn underwent nasotracheal intubation and high - frequency oscillatory ventilation , positioning of a nasogastric tube , and chest x - ray that confirmed prenatal diagnosis . during the first day of life ,\nthe patient maintained clinical stability , so we decided for surgical correction through thoracoscopic approach on the second day of life .\na 5-mm trocar was positioned in the fifth intercostal space over the middle axillary line , and two further operative trocars ( 3 mm , reusable ) were placed in the sixth intercostal space over the anterior and posterior axillary line , respectively .\ncapnothorax was created with a 6mmhg pressure and 0.5l / min flow , and maintained with intermittent insufflation to reduce side effects of co2 absorption .\nonce entered in the pleural cavity , we noted a diaphragmatic hernia with a sac .\na basal extralobar sequestration was also detected and removed after ligation of the feeding artery with two endoloops ( fig .\nthe diaphragmatic defect was repaired with an interrupted 3/0 braided polyester suture ( ethibond ) ( figs . 2 and 3 ) .\nthe patient underwent first follow - up chest x - ray after 2 months , and she is currently asymptomatic without radiologic signs of recurrence ( 6-month follow - up ) . \n\nps includes two forms : intralobar ps ( within the normal parenchyma ) , which is the most common form , and extralobar pulmonary sequestration ( eps).1 eps has its own pleural covering and can be located inside or outside the thorax .\nthe associations are more common in the extralobar type and include congenital pulmonary airway malformation , configuring a lesion termed as hybrid lesion , congenital heart disease , and cdh in up to 15 to 40% of cases.7 \n 8 \n 9 \n 10\na possible explanation is the interference related to the presence of a sequestered lung mass with the fusion of diaphragmatic components ( mechanical obstacle).7 \n 11 \n in recent years , there has been speculation on the prognosis associated with the two simultaneous defects ( cdh and ps).7 ps can be associated with pulmonary hypoplasia , and being a space - occupying lesion , it could constitute a further obstacle to lung development.3 \n 8 \n indeed , the prognosis of ps combined with cdh remains unclear , and although there is not sufficient evidence regarding the influence of ps on cdh prognosis , some authors hypothesized that ps acts as a protective factor during pregnancy and probably improves the prognosis of patients with cdh.7 two possible explanations for this improved outcome may be given : ( 1 ) ps acts as an anatomical barrier to the rise of the abdominal viscera ; ( 2 ) ps causes a mediastinal shift leading to an underestimation of lhr , thus distorting the prognosis that seems poorer.7 \n prenatal identification of both cdh and ps is possible , and frequently occurs.7 in our case , prenatal diagnosis of concurrent cdh and ps was not possible probably because herniated organs obscured the presence of a sequestered lung mass .\nthe treatment of choice of a symptomatic eps in addition to a cdh is surgical excision.1 \n 2 however , some authors recommend observation of asymptomatic eps , as these lesions rarely produce complications.12 we believe that resection should be the treatment of choice in all cases since there are hybrid lesions misdiagnosed as pure sequestrations and one can never be sure that the lesion will remain asymptomatic.4 the most frequent argumentation for removal is the prevention of recurrent infections and malignancy .\nmalignancy has been reported to be associated to cystic lesions , in particular to type i congenital cystic adenomatoid malformation in 1% of cases.12 although the risk is quite low , in case of recurrent infections or neoplastic evolution , the previous wait and see approach would be difficult to justify . regarding the surgical approach , minimally invasive alternatives to the traditional surgical technique have been recently proposed , although the best approach to cdh is controversial.2 recently , hypercapnia and acidosis during thoracoscopy in newborns have been reported.13 \n 14 in our case , we used co2 insufflation at the beginning of the procedure to facilitate reduction of herniated organs only for brief periods to improve visibility .\nthe distinction between a diaphragmatic hernia with sac and a congenital localized eventration may be difficult .\nsac removal seems to be associated with a lower recurrence rate,15 but during thoracoscopy the presence of a sac can facilitate reduction , can lessen visceral trauma , and keeps the two cavities separate.2 according to a recent survey among the international pediatric endosurgery group members,16 22% of surgeons declared to leave the sac in place during the thoracoscopic repair of cdh , so this approach is quite accepted even if in a minority of cases .\naccurate closure of this vessel is mandatory to avoid postoperative bleeding , which can be life - threatening.17 in case of eps , vessel sealing can be achieved with different devices such as ligasure , clips , and ligation . in this case , since the eps was of limited size , we closed the feeding artery with two endoloops and cut the vessel with cold scissors to avoid thermic damage of the ligatures\n. we would probably have missed the ps using a different surgical approach ( classical laparotomy ) , as during the laparotomic approach the posterior position of the diaphragmatic defect makes it hard to inspect the entire hypoplastic lung that is atelectatic and displaced in the upper part of the chest .\nthe thoracoscopic approach for cdh offers the advantage to easily diagnose and treat associated lung lesions .\nthe case report describes the usefulness of thoracoscopy as diagnostic and therapeutic tool in case of diaphragmatic hernia associated with undiagnosed lung malformation .\nthoracoscopy allows to explore thoracic cavity looking for lung lesions that are associated to diaphragmatic hernia in 1540% of cases and to remove them .", "answer": "we report the case of a neonate affected by prenatally diagnosed congenital diaphragmatic hernia ( cdh ) , treated by thoracoscopy . during the procedure , we detected an associated extralobar pulmonary sequestration ( eps ) , which was preoperatively undiagnosed , and we removed it . \n eps has been shown to be associated with cdh in up to 15 to 40% of cases . \n a possible explanation hypothesized is that pulmonary sequestration , which develops at 4 to 5 weeks of gestation , can disturb the fusion of the diaphragm and closure of the pleuroperitoneal canal . \n the thoracoscopic approach permitted us to identify the thoracic eps that probably would have been otherwise missed .", "id": 439} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n musculoskeletal disorders are one of the most common causes of occupational injuries and disability in industrialized nations and developing countries ( 1 - 3 ) . a variety of risk factors are involved in the occurrence of the damage that can be divided by physical factors such as poor posture , ergonomics , lifting , and carrying heavy loads and working with repetitive movements ( 4 ) , psychological , organizational , and individual factors ( 5 )\n. these disorders mainly occur in the upper extremities such as hands , wrists , arms , shoulders , neck , and waist ( 6 ) .\nthese disorders occur due to repetitive movements that led to the injury of nerves , tendons , joints , cartilage or disks between the vertebrae ( 7 ) .\nfactors that cause these disorders are awkward posture , repetitive movements , and excessive force .\nthe signs of musculoskeletal symptoms are muscle pain , discomfort , numbness down , burning , tenderness , swelling , limited range of motion , and loss of power . a long repetitive movement of the body ( 8) causes these pains .\naccording to the previous studies , there is a significant relationship between musculoskeletal disorders and repetitive motion .\nseveral professionals such as surgeons and personnel of the operating rooms are at risk of these symptoms .\nthe surgeons perform the surgery in a standing position , and the hands are generally in motion in surgery .\nsometimes a fixed posture continues for hours and the pressure exerted by the musculoskeletal organs is too high ( 11 ) . over time , the continuous exposure to biomechanical and psychosocial stressors may intensify the musculoskeletal injuries in the workplace . because surgery is often subtle , sensitive , and time - consuming ,\nergonomics aims at helping the surgeons to work without feeling any pain , or stress , and with less error ( 12 ) .\nnowadays , various surgical procedures are done such as open surgery , laparoscopy , and microsurgery ( 13 ) .\nthe body posture of the surgeons during open surgeries is described as a head - bent and back - bent posture .\nsurgeons maintain this posture for long periods ; and as a result , they experience physical discomfort during and after the surgery ( 13 ) . during laparoscopic procedures , the body movement of the surgeon is very limited , resulting in a more static upright body posture compared to open surgery ( 13 ) . due to the position and depth of the incision during open surgery , surgeons have a fixed work posture , tending to work with arms abducted and unsupported ( 14 ) .\nfor instance , repetitive motion of the wrist in laparoscopic surgery , and neck static posture in microsurgery could cause musculoskeletal disorders ( 14,15 ) .\nin addition to improper posture due to ergonomics , repetitive movements of the hands and wrists , neck and shoulders , and excessive force can ultimately cause or exacerbate these effects ( 16 ) .\naccording to healthcare professionals , multiple ergonomic risk factors in the operating rooms can lead to or aggravate musculoskeletal symptoms .\nmoreover , no comprehensive study has been conducted to evaluate and compare the ergonomic risk factors in these 3 types of surgeries .\nthis study aimed at evaluating the role of various ergonomic risk factors in the frequency or resonance frequency of musculoskeletal symptoms in surgeons who perform surgery ( open surgery , laparoscopy , and microsurgery ) in a hospital of iran university of medical sciences . \n\neighty - one male surgeons who consistently worked at milad hospital in tehran participated in this study .\neach of these surgeons exclusively conducted one of the 3 types of open surgery , laparoscopy , and microsurgery . after interviewing the surgery team , to determine the prevalence of musculoskeletal symptoms , the nordic questionnaire ( a questionnaire made by kurinka et al . at the institute of occupational health in 1987 ) was used ( 17 ) . in this study\ndemographic information such as age , height , weight , work experience , and number of hours per day were added to the questionnaire .\nto estimate and evaluate the ergonomic risk factors in each of these three types of surgery wera method was used .\nthe wera covers an extensive range of physical risk factors including posture , repetition , forceful , vibration , contact stress , and task duration , and it assesses the five main body regions ( shoulder , wrists , back , neck and legs ) ( 18 ) .\neighty - one surgeons who performed the 3 following types of surgeries participated in this study : open surgery ( n=26 ) , laparoscopy ( n=28 ) , and microsurgery ( n=27 ) .\neach of the surgery types was observed using the wera tool . during the surgery ,\nobservation of the workplace was carried out by recording the surgeries using a video camera .\nthe three types of surgery were observed and videotaped to collect data for the wera assessment .\nthe angle of the body segments relative to the vertical position was estimated ( shoulders , wrists , back , neck and legs ) using the video tapes ( 18 ) .\nthe participants were middle aged and experienced ( 5.4 years of work experience ) . \n \n\ntable 2 demonstrates the prevalence of musculoskeletal disorders that the surgeons experienced during the past 12 months .\nthe prevalence of symptoms in the neck , back , shoulder , and arm was high ; and a high percentage of the participants involved in all the 3 types of surgeries ( open surgery , laparoscopy , and microsurgery ) .\nno significant difference was found in the prevalence of musculoskeletal symptoms in the body of the surgeons performing these 3 types of surgeries . \n *\nfriedman two - way analysis of the variance test \n table 3 displays the evaluations of the wera scores .\nthe average of wera final score is 40.11 , representing an upward risk for musculoskeletal disorder in 3 types of surgeries . in this study ,\nthe wera score of laparoscopic surgery had a significant relationship with back problems ( r=0.61 , p=0.02 ) , wrist ( r=0.53 , p=0.03 ) , and neck ( r=0.49 , p=0.02 ) .\nmusculoskeletal disorder had a significant relationship with the wera score ( r=0.48 , p=0.02 ) in open surgery , and ( r=0.46 , p=0.04 ) microsurgery . \n\n\n the aim of this study was to evaluate the relation of musculoskeletal disorders and ergonomic risk factors based on wera method in 3 types of surgery among the surgeons who were working in tehran 's hospitals . \n \n in this study , it was found that specified ergonomic risk factors , based on evaluating by wera , has a high impact on the prevalence of musculoskeletal symptoms . on the other hand ,\nthe type of surgery was the main cause of musculoskeletal disorders among surgeons who participated in this study . in a study on the prevalence of musculoskeletal symptoms in surgeons\n, it was found that the highest prevalence was in the lower back , neck , and hands due to poor postures of the surgeons during surgery ( 19 ) . in another study ,\nthe most important cause of arthritis pain and disability was found to be long - term operating mode or standing back for long hours ( 11 ) .\ntherefore , the results of this study are consistent with those of the previous studies on the prevalence of musculoskeletal symptoms in surgeons .\nmusculoskeletal disorder is more common in laparoscopic surgery and open surgery due to incorrect posture , such as the need to bend neck and back ( 20 ) . on the other hand\n, the prevalence of musculoskeletal symptoms in wrist of the surgeons had a direct relationship with instruments in this study , which is consistent with the results of previous studies ( 21 ) .\nimproper use of hand tools in the surgery caused musculoskeletal symptoms and back pain , especially in awkward postures ( 22 ) . in a study conducted on surgeons , the most complaints of the surgeons were related to limbs shoulder , wrist , and waist ( 23 ) . in another study ,\nthe highest prevalence was in the back , neck , and wrists , causing adverse deviation of the wrist posture from the normal posture ( 24 ) . \n \n among the most important tools used in laparoscopic surgery is grasper / loop , which causes poor posture of the body .\nin addition , looking into a monitor for a long time increases the risk of musculoskeletal symptoms in laparoscopic surgeries in the cervical region ( 25 ) .\nmoreover , working with the surgical microscope for a long - time , improper postures , and improper seating increase the prevalence of musculoskeletal symptoms in the back and neck muscle areas while performing microsurgery ( 26 ) . \n \n\nthe results of this study revealed that the prevalence of musculoskeletal symptoms was high among the surgeons .\ntherefore , it is necessary to take action to solve this problem by using appropriate ergonomic tools , management solutions , and suitable design of surgical instruments . a standing - sitting ergonomic chair could be used to prevent back pain in open surgery . moreover , using a suitable chair can prevent improper postures . to prevent wrist musculoskeletal symptoms , surgical tools with ergonomic design and soft rubber handle\ndepending on the type of surgery training , using appropriate seats and ergonomic instruments are the best solution to reduce musculoskeletal symptoms in the surgeons . \n\n\n the results of this study revealed that the prevalence of musculoskeletal symptoms was high in 3 types of open surgery , laparoscopy , and microsurgery among the surgeons .\nin addition , it was found that these symptoms were more prevalent in the neck , waist , and hands .\ndepending on the type of surgery , teaching appropriate methods , using equipment properly , and using proper ergonomic seats are the best strategy to reduce musculoskeletal symptoms in surgeons .", "answer": "background : musculoskeletal symptoms are the main cause of loss of working time , and increase in labor costs . \n poor posture is the most important risk factor for work - related musculoskeletal symptoms . \n this study aimed at evaluating the role of ergonomic risk factors in different surgical ( open surgery , laparoscopy , and microsurgery ) in the frequency or resonance frequency of musculoskeletal symptoms . \n\n \n methods : this descriptive - analytic study was conducted on 81 surgeons in a hospital in tehran . in this study , the prevalence of musculoskeletal symptoms was evaluated using the nordic questionnaire \n . moreover , workplace ergonomic risk assessment method ( wera ) was used to evaluate ergonomic risk factors in 3 types of open surgery , laparoscopy , and microsurgery . \n\n \n results : the results revealed that the prevalence of musculoskeletal symptoms of the neck , back , shoulder , and arm is high in surgeons ( over 75% ) . \n the mean final score of wera was 40.11 , representing the high risk of the 3 types of surgery for the prevalence of musculoskeletal symptoms . \n results revealed that the prevalence of musculoskeletal symptoms in the neck , waist and wrists had a significant relationship with the body posture in the 3 types of open surgery , laparoscopy , and microsurgery ( p<0.05 ) . \n\n \n conclusion : in the present study , the prevalence of musculoskeletal symptoms was high in the neck , waist , and hands surgeries . \n depending on the type of surgery , teaching correct working methods , using proper seats and ergonomic equipment are the best strategies to reduce musculoskeletal symptoms in the surgical profession .", "id": 440} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n acute intussusception is one of the most common causes of acute abdomen in infants .\nmanagement includes both surgical and non - surgical methods , with gradually increasing importance recently being accorded to the latter .\nconservative measures , including hydrostatic reduction , are the methods of choice for initial management . though widely accepted , the expertise is still not widely available , especially in developing countries .\n\n a six - month - old child presented with complaints of repeated episodes of vomiting that contained only ingested milk .\nthis was associated with three episodes of loose stools , initially watery and later with fresh red blood per rectum with jelly - like consistency .\nthere was no history of fever , decreased urine output , lethargy , abnormal body movements , or difficulty in breathing .\nher immunizations were fully up to date with no history of rota virus immunization . \n \n on admission\nabdominal examination was remarkable for an ill - defined mass that could be felt in the right hypochondrium .\nshe was initially kept nil per oral and started on conservative measures , including antibiotics .\nan urgent abdominal ultrasonography was done , which showed a round mass - like lesion giving a target appearance in the right hypochondrium ( suggestive of ileocolic intussusception ) .\nshe was taken for immediate intervention , and as per surgical opinion , a hydrostatic reduction under radiological guidance was started . \n \n\nthe child was first stabilized using intravenous fluids to treat dehydration , and a pre - procedure x - ray abdomen was performed to rule out intestinal perforation .\nthe procedure was done in the ultrasonography room in the presence of a treating physician and a pediatric surgeon . without using any sedation ,\na 16 f foley catheter was inserted into the rectum in the supine position and the balloon was gently inflated while maintaining a tight anal seal . \n \n\nthe patient s vitals , which included abdominal girth and distension , were monitored throughout the procedure .\nlactate solution , warmed to body temperature , was then slowly introduced into the catheter through a bag hanging at a height of approximately 100 cm . during reduction ,\nthe intussusceptum was observed under continuous ultrasound guidance as it proceeded to the cecum and then reduced across the ileocecal valve ( figures 1 - 4 ) . \n \n\nileal loop ( star ) within ascending colon ( arrow ) , longitudinal view . \n \n\nthis was associated with the patient s improved condition , which included less crying and irritability .\nthe parents were told about the possibility of recurrence and asked to pay close attention for the onset of symptoms . \n\n\n acute intussusception is defined as the telescoping of the proximal bowel ( intussusceptum ) into the distal bowel ( intussuscipiens ) .\nthe usual locations include the ileocolic region and ileocecal junction , which comprise the majority of cases .\nintussusception mostly presents between four months and two years , while the peak incidence is found around middle infancy . \n \n\ndiagnosis usually needs a high suspicion on the part of the treating physician , as presentation can be quite varied , including irritability , vomiting , and poor feeding .\ncharacteristic manifestations include crying episodes , fresh red blood in stools ( hematochezia ) , and a mass in the abdomen .\ndifferential diagnoses include acute gastroenteritis , dysentery , sepsis syndrome , and volvulus , amongst others .\nthe diagnosis is usually confirmed sonographically , which is highly accurate and has a reported sensitivity that exceeds 90% .\nvarious signs have been described in the literature , depicting intussusception as an abdominal mass with a target sign on the transverse section , a pseudokidney ( or sandwich sign ) on the longitudinal section , and a crescent - in - doughnut sign on axial images . \n \n\nthe management of intussusception has seen a paradigm shift in recent years . in the past , the preferred non - surgical method involved use of a barium enema for reduction , followed by the air insufflation method . \n \n\nhydrostatic reduction using ultrasound - guided saline reduction has recently gained acceptance as the procedure of choice for initial nonsurgical management of intussusceptions in children .\nthis popularity can be attributed to the avoidance of radiation exposure to the child and the treating team , as well as to the high success rates that have been achieved . \n \n\nthere is still some controversy regarding the exact method of the procedure , which can be attributed to the poor training of physicians and to the general belief that intussusception is entirely a surgical problem , especially in developing countries .\nthis procedure should be undertaken with a close liaison between pediatrics , pediatric surgery , and radiology teams to obtain the best results .\nthe surgeon and physician should always be present at the time of reduction for clinical monitoring . \n \n\nafter adequate optimization , including temperature controlled settings , the procedure should ideally be undertaken without any sedation .\nthis is helpful for assessing a successful reduction using clinical criteria , as described later . \n \n\nwe used ringer s lactate due to its near physiological constitution , avoiding the risk of chemical peritonitis due to a barium enema or tension pneumoperitoneum due to an air enema , as seen in cases of intestinal perforation .\nthe risk of intestinal perforation following such a procedure is rarely encountered due to less hydrostatic pressure exerted and an even amount of pressure exerted on the bowel walls as compared to air insufflations . even if intestinal perforation occurs\nwe chose 100 cm h2o pressure to lessen the risk of perforation , though different studies have used a wide range of pressures ( 75 to 125 cm h2o).6 , \n 9 \n \n the main ultrasonographical criteria of successful reduction is the flow of the fluid from the cecum into the terminal ileum .\ngeneral improvement in the clinical profile of the patient including relief from crying , stable vitals , increasing abdominal distension during the procedure ( which indicates filling of the small bowel ) , and the disappearance of the abdominal mass , should also be given due consideration when deciding to terminate the procedure . \n \n\na repeat ultrasound should always be done after the procedure as the chances of recurrence is high , especially in the immediate post - procedure period .\n, this method should be undertaken as teamwork , and not considered the work of a single specialty , which is the best way of treating the patients according to the standards of today .", "answer": "we present a case of infantile intussusception treated successfully using hydrostatic reduction , highlighting the importance of non - surgical techniques as the first line of management for this entity . \n physicians should strive for mastery over such techniques by extensive training to prevent unwanted surgical procedures in such cases .", "id": 441} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmllerian anomalies are congenital defects of the female reproductive tract resulting from failure in the development of the mllerian ducts and their associated structures\nsymptoms appear principally during adolescence or early adulthood , and affect the reproductive capacity of these women .\nwhen clinically suspected , investigations leading to diagnosis include imaging methods such as hysterosalpingography , ultrasonography , magnetic resonance imaging , and cystoscopy .\na 25-year - old nulliparous lady , presented to the gynecology opd with complaints of inability to conceive .\nshe was married for 7 years , cohabiting since 5 years . at 16 years of age , she consulted a local doctor in her village for primary amenorrhea and cyclical pain in abdomen , where some operative procedure was done . since then the patient has passage of blood mixed urine periodically every month for 2 to 3 days with suprapubic abdominal pain .\nexternal urethral meatus appeared dilated , and there was blindly ending vagina approximately 3 cm in length . on per rectum\nexamination , uterus appeared normal in size and there was no bulge felt below it to suggest any collection . on investigations ,\nthe ultrasound showed normal uterus with endometrial thickness 9.5 mm , ovaries were normal , and bilateral kidneys were also normal .\nmri of abdomen showed normal uterine body and cervix with small amount of fluid in endometrial cavity , endocervical cavity , and in upper part of vagina ; below that there was a transverse vaginal septum of about 3.5 cm in thickness .\n[ figure 1 ] on cystoscopy , a fistulous opening of approximately 2 mm was seen below the internal sphincter of urethra through which menstrual blood was seen coming out ; the bladder and ureteric orifices were normal .\nvaginoplasty and repair of fistulous communication between the genital tract and the urethra was planned for the patient .\nthe mri shows uterus with cervix and upper 2 cm of vagina containing some blood products .\nthere is a septum between the upper and lower part of vagina ( the lower part identified by tampon in vaginal canal ) the woman was subjected to operation using abdominoperineal approach .\non laparotomy , uterus was normal in size , bilateral tubes were present , and ovaries were normal .\nthe methylene blue dye was injected into the fundus of the uterus ; dye was visualized coming out of urethra by the side of the indwelling catheter . from the perineal approach\n, a transverse incision was made through the vault of the short vagina , the dissection was done upward in the connective tissue between the bladder above and rectum below and vaginal space was created .\nafter sharp and blunt dissection , cervix was visualized as dye was coming through it .\nthe urethrovaginal fistulous tract was identified and repair was done in two layers . over the raw area of vagina ,\nthe mould change was done after a week ; the amnion graft had successfully taken up .\nthe patient was found to be fine at follow - up after a month , with no hematuria and normal menstruation .\nshe was explained about the fertility period and asked to come at 3 monthly follow - up .\nwhen a mullerian duct becomes obstructed , the patient may present with an abdominal mass and dysmenorrhea .\nif the patient is not treated in a timely fashion , the consequences can be severe , extending even to infertility . in this case\n, there was transverse vaginal septum in the upper part of vagina leading to hematocolpus and amenorrhea .\nan iatrogenic fistulous tract was probably created which led to cyclical hematuria . magnetic resonance imaging ( mri )\nis the mainstay in imaging for the evaluation of mullerian agenesis and is considered a very useful diagnostic tool . in our case ,\nmri determined the precise mullarian anomaly giving us the details regarding the presence of normal cervix with precise length of vaginal septum to help us judge the prognosis and success of the operative procedure , but we got no information about the fistulous communication as it was quite fine and narrow .\nthe site of the opening of fistulous tract in the urethra was apparent on cystoscopy and led to the assumption that the other end tract opened in the vagina .\ntherefore , apart from mri , cystoscopy played a major role in determining the anomaly in this case . upon literature review of cases with genitourinary fistula\nthe fistula in that case , however , was congenital , unlike our case in which it was iatrogenic in all probability .\nit also presented with cyclical hematuria with no incontinence of urine due to imperforate hymen .\ncongenital vesicouterine , cervicovesical , and vesicovaginal fistula associated with other mullarian anomalies has also been reported in literature.[46 ] iatrogenic fistulous communication between the genital tract and the urinary tract , known to occur as a complication of cesarean section , has been described in literature as youssef 's syndrome . \nit is characterized by cyclical hematuria , absence of vaginal bleeding , and complete urinary continence . in all these reports\nin which there was a fistulous communication between the urinary and the genital tract , cystoscopy , hysterosalpingography , and dye test were required for confirmatory diagnosis and only computerized tomography ( ct ) or mri did not give the full clinical picture .\nthis report highlights the diagnostic and therapeutic challenge faced by the clinician in dealing with a fistulous genital and urinary tract communication with obstructing transverse vaginal septum .\nincreasing awareness of this rare entity calls for more meticulous evaluation before any surgical intervention in patients with complex genitourinary anomalies .", "answer": "we present a case of iatrogenic urethrovaginal fistula with transverse vaginal septum . \n the patient presented with cyclical hematuria and infertility . \n the vagina was blind - ending . \n the magnetic resonance imaging ( mri ) showed normal uterus with transverse vaginal septum . \n the cystoscopic examination during cyclical hematuria revealed bloody efflux through a small fistula below the internal urethral sphincter . \n vaginoplasty and repair of the urethrovaginal fistula was done . \n the vagina was reconstructed using an amniotic mould . \n the report emphasizes the importance of mri and cystoscopy in diagnosing such rare and complex anomalies .", "id": 442} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nheart transplantation continues to provide patients with end - stage heart disease with extended survival with a half - life of 9.3 years between 2000 and june 2008 . .\nhowever , despite substantial advancements in immunosuppression , patients continue to be at significant risk for allograft rejection early after cardiac transplantation .\nthe two recognized forms of allograft rejection are acute cellular rejection and antibody - mediated rejection ( amr ) .\nwhile acute cellular rejection has historically been the most common cause of allograft dysfunction , amr has only recently become widely accepted . during the 2004 international society of heart and lung transplantation ( ishlt ) ,\ncellular rejection grades were revised and amr was formally defined . in april 2010 , a publication from the ishlt consensus conference assessed the status of amr in heart transplantation and a pathologic grading scale was devised . despite the advent of new technology , such as gene expression profiling and echocardiograms , endomyocardial biopsy remains the standard for detecting rejection . to minimize the risk of a false negative , multiple specimens ( usually 35 ) are obtained from 3 different sites . though rare\n, false negatives do exist either through sampling error , artifact , quilty lesions , or pathology misread .\nprior to the 2010 consensus conference , hemodynamic compromise , in the absence of acute cellular rejection , was termed biopsy - negative rejection .\nalthough the prevalence of the so - called biopsy - negative rejection has declined with the clinical diagnosis of amr , there are incidences of patients who present with cardiac dysfunction ( left ventricular ejection fraction , lvef 45% ) but have no biopsy findings of cellular or antibody - mediated rejection .\nsince the outcome of patients with bnr ( which includes cardiac dysfunction ) has not been well established , we sought to review the characteristics and treatment response of patients who have developed bnr after heart transplantation .\nwe retrospectively reviewed our cohort of patients who underwent heart transplantation between 2002 and 2012 and found 12 cases of bnr in 11 heart transplant patients , as defined by patients presenting with cardiac dysfunction , characterized by lvef 45% , and who had no biopsy findings of cellular rejection or amr .\nas severe infections are also known to cause left ventricular dysfunction , patients with a clear clinical picture of sepsis with fever , increase in white blood count , or positive cultures were excluded .\ncontinuous variable was presented as mean standard deviation while categorical variable is presented as percentages .\nwe identified 11 patients who underwent heart transplantation between 2002 and 2012 and were treated for bnr .\nnone of the bnr patients had previous blood transfusion or previous transplant . 5 ( 45% ) patients had a previous vad placement and 1 ( 9% ) patient was african american .\nthe baseline immunosuppression medications are as follows : 5 patients ( 45% ) underwent induction therapy with antithymocyte globulin ( atg ) , 9 patients ( 82% ) initiated with tacrolimus and mycophenolate mofetil , 1 patient ( 9% ) initiated with cyclosporine and mycophenolate mofetil , and 1 patient ( 9% ) initiated with cyclosporine and azathioprine .\n2 patients switched to cyclosporine from tacrolimus because of reduced seizure threshold ; 1 patient switched to a renal sparing protocol of sirolimus with mycophenolate mofetil because of renal function concerns .\nthe 12 cases of bnr presented with an average lvef of 34% 10% and 11 ( 92% ) treated cases occurred during the first - year after transplant ( table 3 ) .\nthe mean time to the first incidence of bnr is 7.8 7.5 months and no patient had treated rejection before onset of bnr except for the patient at the second onset . among the 106 biopsies that have been done before bnr , 24 ( 23% ) demonstrated low grade acute cellular rejection ( 1r , 1a , or 1b ) and 1 ( 0.9% ) showed suspicious antibody - mediated rejection ( amr 1 ) . de novo circulating antibodies developed in 3 cases ( in 3 patients ) and 1 of them had donor - specific antibodies . 4 out of the 12 cases presented with lvef 35% and presented with heart failure symptoms . of these 4 heart failure cases ,\n2 required inotropic support both received intravenous ( iv ) methylprednisolone ( 500 mg1000 mg per day for 3 days ) , atg ( 125150 mg per day for 35 days ) , and iv immunoglobulin ( ivig , 70 g per day for 3 days ) , followed by oral corticosteroids ( prednisone 80100 mg per day bolus and taper ) .\nfor the remaining 2 patients who presented with heart failure symptoms but did not necessitate inotropes , 1 was treated with atg and iv methylprednisolone followed by prednisone bolus and taper and the other was given iv methylprednisolone followed by prednisone only .\nfor the 8 out of 12 cases without heart failure symptoms , 7 were treated with only high dose oral corticosteroids .\noverall , 7 cases ( 58% ) ( in 7 patients ) favorably resulted with return to normal left ventricular function ( lvef of 57% 6% ) within a mean of 14 10 days from the initial negative biopsy .\nof these 7 patients , one expired approximately 6 months after the date of the normalized lvef and another one expired approximately 4 months after the date of normalized lvef . the remaining 5 cases ( in 5 patients , including 1 patient 's second case of bnr ) maintained persistent left ventricular dysfunction beyond 90 days .\na flow chart of treatment and effect could be found in figure 1 . in summary ,\nthe lvef status at 90 days is as follows : 5 cases ( in 5 patients , including 1 case as second bnr on a patient ) had persistent lv dysfunction , and 7 cases ( in 7 patients ) experienced normalized lvef .\nas our understanding of the biological mechanisms underlying cardiac allograft rejection increases , the number of undiagnosed rejection decreases . the concept of bnr has evolved from its initial definition as hemodynamic compromise in the absence of acute cellular rejection to its current definition of patients presenting with cardiac dysfunction in the absence of biopsy findings of cellular rejection or amr .\namr has changed from being suggested as bnr to its own ishlt biopsy grading scale . however , even though the majority of rejection episodes of unclear etiology have now been resolved to be cases of amr , there are still cases where the biopsy findings are inconsistent with the clinical prognosis , that is , patients with a decrease in lvef with no biopsy findings of rejection , cellular , or humoral . due to the inconsistencies of endomyocardial biopsies , the existence of bnr is questioned .\nthis argument is furthered by the fact that prior to the 2010 amr consensus conference , 1020% of cardiac allograft recipients were diagnosed with bnr when in actuality the majority of patients most likely experienced amr .\nthis brings up the question of whether bnr should exist as a separate category of rejection or is merely a by - product of the problems inherent with endomyocardial biopsies . in one case study ,\nsampling error or nonuniformity of histopathologic changes resulted in a false - negative biopsy . in this case study ,\na heart transplant recipient with repeatedly unremarkable endomyocardial biopsies and a negative evaluation for humoral rejection was found to have severe subepicardial myocyte necrosis with classic cellular rejection in the subsequent autopsy .\nthis is contrary to other studies which have found that rejection is evenly distributed throughout the right ventricular endomyocardium .\nalthough endomyocardial biopsy is the primary resource to diagnose acute rejections in all the cases discussed in this study , there are a few noninvasive diagnostics that have been demonstrated to be helpful in diagnosing acute allograft rejection after heart transplantation . in one multicenter clinical trial , pham et al .\nreported that using gene - expression profiling to monitor rejection for patients 6 months after heart transplantation was not associated with increased risk of serious adverse outcomes and could reduce the need for biopsy . in two pilot studies , wu et al .\napplied cardiac magnetic resonance ( cmr ) in vivo to detect immune - cell infiltration at sites of rejection by monitoring macrophages .\nthe investigators subsequently developed a functional index from local strain analysis and proved it to be correlated with rejection grades [ 8 , 9 ] .\nalthough clinical applications have not been implemented , cmr was demonstrated to be capable of providing the rejection status of whole - heart perspective , and thus might be a potential tool of optimizing diagnosis of bnr .\nanother potential tool is speckle - tracking 2-dimensional strain echocardiography ( 2dse ) . by using rat cardiac transplantation models , pieper et al\n. demonstrated that 2dse was able to differentiate myocardial function between rejection in allografts and nonrejection in isografts .\nperhaps bnr is another form of amr but due to the newness of amr and the lack of a complete understanding of amr , no definite conclusions can be made . despite the ishlt revised biopsy rejection scale ,\nthis revised definition of bnr has been noted to result in a decrease in 3-year subsequent survival , lower subsequent freedom from cardiac allograft vasculopathy ( cav ) , and a decrease in freedom from nonfatal major adverse cardiac events ( nf - mace ) .\nprevious studies characterized bnr as occurring on average 43 38 months following transplantation while the data collected in our study indicates that the time to the first incidence of bnr is 7.8 7.5 months . the mechanism associated with bnr\nunfortunately not too many reports in the field looked at the treatment protocols for bnr . in our single center experience , who patients presented with heart failure symptoms\nwere given more aggressive treatment , that is , atg , iv methylprednisolone , and ivig while patients without heart failure symptoms were mostly given prednisone bolus and taper only . as bnr is an infrequent phenomenon , of which there is considerable debate regarding its validity , further work needs to be instigated on whether there is a correlation between different factors and bnr episodes .\noverall , from this set of data , it is inconclusive as to whether or not there are any characteristics of bnr that differs from other types of rejections .\na point of interest in this study is the patient who experienced two episodes of bnr . due to the small sample size , it is uncertain whether having one episode of bnr increases the risk of recurrent bnr episodes . during the first bnr episode ,\nin contrast , it took the patient 6 months to experience a return to normalized lvef ( 51% ) during the second bnr episode .\nfor the first episode of bnr , there was a favorable return to normal cardiac function following treatment with oral corticosteroids bolus and taper .\nin the case of the second episode of bnr , ivig was given instead which led to an increase in lvef , although it took a longer time ( 6 months ) for the patient to experience a return to the range of normalized lvef .\nprior to experiencing normalized lvef the patient 's lvef remained in the 40% range , fluctuating between 43% and 48% .\nthe repeat bnr patient was the only african americans in this study and did not experience normalized lvef at 90-day after second onset .\nafrican americans have been reported to have a higher risk of rejection after transplant compared to any other race due to their unique metabolism in regard to immunosuppression [ 14 , 15 ] .\na possible immunosuppression regimen with respect to bnr could require more aggressive treatment , employing the use of atg and ivig in addition to steroids .\npotential cause for this second onset of bnr could be the combined factor of this patient not receiving an adequate treatment for the second bnr and the ethnicity of the patient . as cases of bnr tend to respond favorably to appropriate rejection therapy 2 ( 17% ) of 12 bnr cases required inotropes and 7 ( 58% ) bnr cases without heart failure symptoms were treated with oral steroid bolus and taper .\nseven of 12 ( 58% ) treated bnr cases resulted in a return to a normal lvef of 57% 6% within a mean of 14 10 days from the initial negative biopsy . due to the small sample size , it is uncertain whether bnr should be considered as a new category in the biopsy grading scale or if it is merely difficult to diagnose based on endomyocardial biopsies alone . if it is the former , then mechanism needs to be elucidated .\nif it is the latter , then perhaps other methods for detecting rejection need to be considered .\nbnr is a rare phenomenon ( 12 cases of bnr in a 10-year period ) and can be a severe form of rejection in that there is cardiac dysfunction .\nhowever , this type of rejection is not apparent on biopsies due to either lack of knowledge regarding further types of rejection or other factors . characteristics of these cases of rejection are described above with most cases responding favorablly to rejection therapy .", "answer": "purpose . \n the most recent international society for heart and lung transplantation ( ishlt ) biopsy scale classifies cellular and antibody - mediated rejections . however , there are cases with acute decline in left ventricular ejection fraction ( lvef 45% ) but no evidence of rejection on biopsy . \n characteristics and treatment response of this biopsy negative rejection ( bnr ) have yet to be elucidated . methods . between 2002 and 2012 \n , we found 12 cases of bnr in 11 heart transplant patients as previously defined . \n one of the 11 patients was treated a second time for bnr . \n characteristics and response to treatment were noted . \n results . \n 12 cases ( of 11 patients ) were reviewed and 11 occurred during the first year after transplant . \n 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin . \n four cases with heart failure symptoms were treated with thymoglobulin , intravenous immunoglobulin , and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper . \n overall , 7 cases resulted in return to normal left ventricular function within a mean of 14 10 days from the initial biopsy . \n conclusion . \n bnr includes cardiac dysfunction and can be a severe form of rejection . \n characteristics of these cases of rejection are described with most cases responding to appropriate therapy .", "id": 443} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nheterogenous vancomycin intermediate staphylococcus aureus ( hvisa ) strains have been reported as indicators for reduced vancomycin susceptibility in s. aureus , and various studies associated its presence with vancomycin treatment failure .\nit has been shown that methicillin resistant s. aureus ( mrsa ) has the propensity to evolve into hvisa phenotype during in vitro exposure to subinhibitory concentrations of vancomycin . during the last decade\n, hvisas had been isolated in many countries including those in south east asia ; nevertheless , in our knowledge , its emergence has not been reported in malaysia . as a pilot study\n, we investigated the prevalence of hvisa among mrsa strains isolated at hospital kuala lumpur ( hkl ) in a 3-month period and determined factors associated with its infections .\nhospital kuala lumpur is the largest hospital in malaysia with the highest mrsa burden in the country . in this hospital\n, vancomycin is used as the standard first line treatment for mrsa infection ; however , recently , its efficacy has been a subject of discussion due to several anecdotal vancomycin treatment failure cases in hospital kuala lumpur .\nwe also wondered if some of the mrsas isolated in the hospital were actually hvisas with reduced susceptibilities to vancomycin that could not be detected by routine microbiological tests used in our hospital diagnostic laboratory . to investigate this , from 25 february to 25\nmay 2009 , we collected a total of 320 index mrsa isolates ( first mrsa isolated from the corresponding patients ) and established them as strains for vancomycin resistance testing . as it is cost , time and labor consuming to perform vancomycin population analysis on all 320 strains to test for heterogenous vancomycin resistance , strains were first screened for the phenotype using glycopeptide resistance detection ( grd ) etest antibiotic strips ( ab biodisk , sweden ) .\nafter grd screening , a total of 8 strains were defined as presumptive hvisa , no visa strain was detected . following that , to confirm the results of the grd screening\ninterestingly , area under the curve ( auc ) analyses of the strains ' population analysis profiles confirmed that 7 out of the 8 tested strains were hvisa ( table 1 ) , giving a prevalence rate of 2.19% . \n\ntable 1heterogenous vancomycin intermediate staphylococcus aureus strains and their corresponding patients in this study.specimen noagegenderprimary diagnosisspecimendiabetes mellitusrenal failuremalignancyadmission to icudays of hospital staydays of iv vcmon beta - lactamarea under curve ratio68214maleright hip osteomyelitisnasal swabnononoyes44 days0yes0.9058253femaleleft diabetic foot ulcerpus swabyesyesnoyes52 days14yes0.9318258maleacute ventriculitiscsfyesnonoyes98 days14yes1.0125220malegluteal sarcoma with hapsputumnonoyesyes24 days10yes0.9097871malepemphigus folliaceouspus swabyesnonono34 days7yes1.012154femaleacute encephalitis with haptracheal aspiratenononoyes32 days14yes0.9646029femalemeningo - encephalitis with hapsputumnononoyes38 days10yes0.98icu , intensive care unit ; iv , intravenous ; vcm , vancomycin ; csf , cerebrospinal fluid ; hap , hospital acquired pneumonia . \n \nicu , intensive care unit ; iv , intravenous ; vcm , vancomycin ; csf , cerebrospinal fluid ; hap , hospital acquired pneumonia .\nall hvisa strains isolated in this study were hospital acquired as they were isolated from their corresponding patients after 48 hours of hospital admission . to determine factors associated with the 7 hvisa infections , demographic data of all corresponding patients of each index mrsa isolate were retrieved from medical records .\nmedical history of each patient such as diabetes mellitus , renal failure , malignancy , together with prescription history of vancomycin and beta - lactam antibiotics ( as these were the only classes of antibiotics prescribed to the corresponding patients of the study isolates during this investigation ) , length of hospitalization and intensive care unit ( icu ) admission were recorded .\ncontinuous variables were then assessed by independent samples t - test , while categorical variables were analyzed using pearson 's chisquare .\ncalculations were performed using statistical package for social science ( spss ) 12.0 ( spss inc . , chicago , usa ) where a p - value of < 0.05 was considered as significant . after performing multivariate linear regression\n, we found that icu admission ( p<0.004 ) , hospitalization of more than 14 days ( p<0.014 ) and vancomycin administration of more than 7 days ( p<0.016 ) were independent factors associated with hvisa infections in our group of patients .\nour findings were in line with those of charles et al . in 2004 , where hvisa / visa infections were found to be associated with longer antibiotic treatment periods and longer hospitalization . in a separate report\nit seems that patients who are severely ill , hospitalized for long durations with icu admissions might have a higher chance of developing hvisa infections .\nas many patients in hkl fulfill some or all of the above criteria , taking it together , we suspect that the prevalence of hvisa in hkl might be high ; however , these strains are not being actively detected by the hospital diagnostics laboratory .\nas hvisa and mrsa with reduced vancomycin susceptibility has been reported to cause treatment failure , given the hvisa prevalence rate detected in this study , it is not surprising that vancomycin treatment failure cases among mrsa infected patients are increasing in hkl . in our study\n, we employed the grd test as a screening tool for hvisa before confirming the resistance with population analysis , and found that the grd etest was fairly specific with only one false positive result .\nin a review , howden and colleagues have reported the test 's sensitivity as 9394% with a 8295% specificity for hvisa detection .\ntherefore , the grd might be considered a good screening tool for hvisa in hospitals where most hospitalized patients are severely ill with long hospitalization durations . once identified as hvisa infected ,\noptimal treatment could be prescribed to the corresponding patient to prevent vancomycin treatment failure , thereby increasing the chance of a good clinical outcome for the patient .\nas the strains used in this study were collected in a short span of 3 months , and that vancomycin treatment failure is on the rise in hkl , we suspect that the actual prevalence of hvisa in this hospital might be even higher .\nwe found the grd test useful for hvisa screening , nevertheless pap - auc analysis still remains the gold standard for hvisa confirmation .\na more comprehensive , case control study involving major hospitals in the country would be important to better understand the significance and distribution of hvisa in malaysian hospitals .", "answer": "in a 3-month study done in hospital kuala lumpur ( hkl ) , 7 out of 320 methicillin resistant staphylococcus aureus isolates were confirmed as heterogeneous vancomycin intermediate s. aureus ( hvisa ) using the glycopeptide resistance detection e - test and population analysis , giving a prevalence rate of 2.19% . \n this is the first report of hvisa in malaysia .", "id": 444} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe cross - sectional study was undertaken in the schools located within the registered rural and urban field practice areas of the department of community medicine , jnmc , aligarh , uttar pradesh , india .\nthe total population of male adolescents ( 10 - 19 yrs ) in all the schools was 2347 , out of which a sample of 410 students ( 205 from the rural schools and 205 from the urban schools ) were selected using probability proportionate to size sampling ( pps ) .\nthe sample size was calculated using the formula , sample size = ( 1.96 ) pq /\nl where prevalence ( p ) = 20% , q = ( 1p ) precision ( l ) = 4% the study tools consisted of a self - developed , pre - tested , semi - structured questionnaire arranged in two parts .\nthe first part of the questionnaire dealing with the child 's sociodemographic background was accomplished by the interviewer , and the second part had a section of aspirations and desires of adolescents including their role models and their future choice of career .\nall participants were reassured about their anonymity by instructing them to avoid writing their names and class section on the questionnaires .\nsocioeconomic class was calculated using a modified form of prasad 's classification of per capita income .\nsimple percentages [ table 1 ] and chi - square test of statistical significance was used for analysis [ tables 2 and 3 ] .\nsociodemographic characteristics role models of in - school adolescents occupational aspirations of in - school adolescents\nmost of the study population was in their early ( 10 - 13 yrs ) and mid - teens ( 14 - 15 yrs ) , hindu , lower to middle socioeconomic status , and living in unitary families with more than 5 family members [ table 1 ] .\nadolescents responded to the question regarding the presence of a role model in their lives with a near total majority ( 95.9% ) .\noverall , the majority ( 62.7% ) of adolescents revealed that their role models were film star ( 34.8% ) and their teachers ( 27.9% ) , parents ( 14.3% ) , sportsman ( 12.0% ) .\npoliticians as the role models were opted by least proportion ( 1.2% ) . in urban and rural schools ,\nthere were significant differences between the choices of the role models ( chi - square = 24.1 , df = 06 , p < 0.05 ) [ table 2 ] . when asked about the desires for the future occupation or job\n, many adolescents ardently responded that they wish to become businessmen ( 27.9% ) , doctor ( 18.6 ) , and engineer ( 14.4% ) .\nothers opted to be a teacher , farmer , police officer , or government servant .\nthe difference between urban and rural adolescents in the occupational desires was statistically significant ( chi - square = 18.9 , df = 08 , p < 0.05 ) .\nmost of the study population was in their early ( 10 - 13 yrs ) and mid - teens ( 14 - 15 yrs ) , hindu , lower to middle socioeconomic status , and living in unitary families with more than 5 family members [ table 1 ] .\nadolescents responded to the question regarding the presence of a role model in their lives with a near total majority ( 95.9% ) .\noverall , the majority ( 62.7% ) of adolescents revealed that their role models were film star ( 34.8% ) and their teachers ( 27.9% ) , parents ( 14.3% ) , sportsman ( 12.0% ) .\npoliticians as the role models were opted by least proportion ( 1.2% ) . in urban and rural schools\n, there were significant differences between the choices of the role models ( chi - square = 24.1 , df = 06 , p < 0.05 ) [ table 2 ] .\nwhen asked about the desires for the future occupation or job , many adolescents ardently responded that they wish to become businessmen ( 27.9% ) , doctor ( 18.6 ) , and engineer ( 14.4% ) .\nothers opted to be a teacher , farmer , police officer , or government servant .\nthe difference between urban and rural adolescents in the occupational desires was statistically significant ( chi - square = 18.9 , df = 08 , p < 0.05 ) .\nthis study highlighted that majority of adolescents have a personality in their minds , whose attributes they follow in their life .\nthough the stage of adolescence is a dynamic period of life with respect to changing attitudes and perceptions , change in their role models might be seen in due course with increasing age and maturity . at\nany given phase of adolescence , their choice of role models may indicate the likings and behavior form of the adolescent . an adolescent may choose a particular role model due to a bouquet of reasons . in this study , the reason given by the majority was related to the image of being ideal with a virtue of righteousness along with the glamour attached to them .\nthis reason may be an indication of choosing film stars as the role model as this virtue is usually shown in the heroes of indian films .\na good teacher also leaves a good impact on the students ; thus , a good proportion chose them as role models .\na small proportion chose parents as role models ; the reasons for this observation need a detailed study . according to a researcher , in their study of adolescents from rural area it was found that film heroes were the role model for 31.3% students , cricketers for 12.61% , and political leaders for 7.83% students and for the rest of the students , parents / teachers were the role models .\nthe pattern of choice was similar as compared to the present study . in another study , fifty - six percent of adolescents identified a role model .\nparent / relative ( 42% ) , non - familial known individual ( 19% ) , and figure or individual available primarily through the media ( 39% ) . among non - familial known individuals were friends ( 56.9% ) , professionals such as doctors or lawyers ( 22.8% ) , teachers ( 15% ) , and clergy ( 1.2% ) . among \nfigure were actors ( 18.5% ) , historical figures ( 5.7% ) , political leaders ( 1.9% ) , comic book characters ( 1.2% ) , and a community leader ( 0.6% ) .\nthe desire of future occupation during adolescent plays an important role in the academic journey of an individual .\noften , it has been observed that putting a foot in wrong shoe is detrimental to the practical life of an individual .\nthe mindset of the society regarding various professions puts an enormous pressure on the adolescents .\nfurther , the ever - increasing competition for some professions also augments the bulk of non - achievers of the competition and leaves them with disappointment and depression .\nprofessionally guiding adolescents according to their likes and dislikes regarding their career could bring down the proportion of otherwise non - achievers . in a study , in response to the question , if you had to start work tomorrow and assuming you had the proper education or training , what kind of work would you most likely choose ? , the following seven themes emerged from the responses of grade seven students : ( a ) professional occupations ( e.g. lawyer , computers , doctor , nurse , architect , counselor ) ; ( b ) glamour occupations ( e.g. athlete , actress , fashion designer , chasing tornadoes ) ; ( c ) trade occupations ( e.g. mechanic , carpenter ) ; ( d ) occupations with children ( e.g. daycare worker , teacher ) ; ( e ) occupations with animals ( e.g. zoologist , wildlife biologist , veterinarian ) ; ( f ) volunteer occupations , and ( g ) service industry occupations ( e.g. chef , bed and breakfast , hairdresser ) . the finding of present study is in accordance with the above - mentioned study as the students revealed various choices for the future profession . in another study , the students who wanted to become doctor were 23.48% , engineer 16.5% , and teacher 24.54% , 14% students wanted to join defense / police services and the rest wanted to join the business / salaried jobs .\nthe reason may be that the majority of study population belonged to the rural area where agriculture and small scale business was more practiced .\nit is observed in this study that although the role model in good proportion of adolescent were film stars , only 2 students desired to be an actor .\nthis observation highlights that the students had rational thinking when it comes to future occupational choices .\nthe above - mentioned studies show that the career choices during adolescent are varied , and all they need is proper guidance to progress with their choice of profession and they might give best results according to the developed capacity in them rather than being depressed .\nthere is greater impact of cinema on the minds of adolescents , which resulted in choosing film actors as their role model .\nthe choice of future occupation was not related to the type of role models but may be influenced by society and family admiration for certain occupations .\nproper guidance in this phase of life in needed to develop rational thinking in adolescents .\nthe permission of this thesis survey was obtained by the institutional board of studies held on 20.08.2002 .\nverbal consent of the principals of the schools selected for the study was received prior to starting the study .\nthe parents of the students were informed about this study in the parent teacher meeting and their consent was obtained by the principal of the school .", "answer": "background : a role model is perceived as worthy of imitation , their selection can indicate significant elements of psychosocial health and self - projection in adolescents . patterns of behavior and lifestyle choices established during adolescence can have immediate and lasting effects on health.materials and methods : cross - sectional study was undertaken in the schools of aligarh , uttar pradesh , india . \n the sample frame was 2347 , out of which a sample of 390 students was studied . \n data collected were entered and analyzed by spss for windows version 10%).results : majority ( 62.7% ) of adolescents revealed that their role models were film star ( 34.8% ) and their teachers ( 27.9% ) , parents ( 14.3% ) , sportsman ( 12.0% ) . \n politicians as the role models were opted by least proportion ( 1.2% ) . \n desire of future occupation was businessmen ( 27.9% ) , doctor ( 18.6 ) , and engineer ( 14.4%).conclusion : nearly all adolescents had a role model . \n there is greater impact of cinema on the minds of adolescents , which resulted in choosing film actors as their role model . \n aspiration of future occupation was not related to the characteristics of the role model .", "id": 445} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchildren constitute approximately 40% of india 's population but information on adverse drug reactions occurring in them is limited .\nphenytoin sodium ( pht ) is one of the commonest antiepileptic drug ( aed ) used in children in india .\nthe drug has wide pharmacokinetic variability and has a narrow therapeutic range that leads to toxicity .\nthere is some evidence of the association of long - term use of pht and toxicity like cerebellar atrophy .\nsuch cerebellar changes have been reported even with the long - term use of nontoxic levels of phenytoin .\n, we report a case of reversible cerebellar atrophy induced by pht in a 10-year - old boy .\nafter initiating therapy with pht 10 years back , he was seizure free for 2 years .\npatient was also occasionally prescribed clobazam , 5 mg , oral , as and when required . the episodes used to last for a brief period of over 6 - 7 days .\nseizures used to occur at every 3 - 4 months interval . the boy had history of birth asphyxia and delay in developmental milestones .\nafter the patient recovered , he was evaluated again due to complaint of difficulty in walking .\ncns examination revealed normal mentation with cerebellar signs including gaze - evoked nystagamus , truncal , and appendicular ataxia .\nmri scan of the brain was advised and it showed cerebellar atrophy as shown in figure 1 .\nserum phenytoin level was high ( 30 mcg / ml ) and pht was withdrawn immediately . patient was started on valproic acid and followed up .\nhowever , a sizeable proportion of patients may develop drug induced adverse effects that include sedation , gum hypertrophy , lymphadenopathy , chorea , ataxia , etc .\nthere are a few reports on cerebellar atrophy after long - term use of pth .\nthese adverse effects are usually reported if the drug serum levels are above the therapeutic range .\nour patient presented with severe cerebellar disorder and he was on the drug for 10 years .\nhence , a regular monitoring for adverse drug reaction should be considered in patients who are on drugs on long term basis .\nthese reactions could be idiosyncratic or dose - dependent which again may be acute or chronic in nature .\nsince most of these effects are reversible , it is important to identify the clinical manifestations related to drug toxicity and to manage them appropriately . also , it warns the need for regular monitoring of plasma concentration , accurate dosing , and identification of adherence issues in patients on phenytoin .", "answer": "epilepsy is an important health problem due to its high prevalence and potential for causing long - term morbidity . \n it is commonly treated in children with phenytoin sodium . \n it has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity . here \n , we report a case of phenytoin - induced cerebellar atrophy in a 16-year - old epileptic boy who presented to the hospital with a viral infection .", "id": 446} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nposterior elbow dislocation is the most common type of elbow dislocation with slightly higher incidence in the male population and they constitute 1025% of all injuries to the elbow among persons with a mean age of 30 years .\nthe human instinct to protect the dominant arm from injury during fall is responsible for a slight predominance for dislocation in the nondominant extremity .\na high index of suspicion should be maintained by the emergency physician in evaluation for neurovascular compromise in all cases with elbow dislocation , especially in cases where the x - ray is normal . in most of the times ,\na simple lateral view x - ray shows the dislocation , and absent radial and ulnar pulses insures that an arterial injury is present . in our case , the x - rays were normal , and the patient had normal pulses on presentation .\na 71-year - old right - handed male presented to our emergency department ( ed ) with left elbow pain after he fell on his left outstretched hand 1 h prior to presentation .\nphysical examination revealed a swollen elbow , with a dusky cold hand ; radial and ulnar pulses were initially felt and were weak in comparison with the contralateral side , but after repeated assessment , the pulses became absent .\nradiographs revealed no fracture or dislocation of the elbow joint ( fig . 1 ) . \n\nfigure 1:posterior splint was applied in ed and x - rays showed no fracture , no dislocation .\nposterior splint was applied in ed and x - rays showed no fracture , no dislocation . as arterial injury was suspected , angiography was done and revealed a brachial artery occlusion proximal to its bifurcation with the presence of some collateral circulation reaching and perfusing the radial and ulnar arteries .\nintraoperatively , the elbow was found to be grossly unstable and easily dislocatable especially on extension .\naccess to the brachial artery was achieved via a lazy s incision across the antecubital fossa , and exploration revealed brachial artery contusion , with intact adventitia and median nerve ( fig . 2 ) . \n\nfigure 2:intact adventitia of the brachial artery ( arrow ) , also the median nerve seen stretched over the articular surface of the distal part of humerus , is intact ( scissors ) .\nintact adventitia of the brachial artery ( arrow ) , also the median nerve seen stretched over the articular surface of the distal part of humerus , is intact ( scissors ) .\nthe anterior elbow capsule was disrupted associated with avulsion of the flexor pronator group from the medial epicondyle .\nas arteriotomy was done , there was an intimal loss over the entire arterial circumference for 1 cm ( fig . \nfigure 3:loss of intima in all the entire circumference of the brachial artery in a 1-cm segment ( arrow ) .\nloss of intima in all the entire circumference of the brachial artery in a 1-cm segment ( arrow ) .\nthe defective part of the artery was excised and repair was achieved by placement of a brachiobrachial end - to - end reversed saphenous bridge ( fig . 4 ) .\nthe time of trauma - to - revascularization was 7 h ; primary wound closure was performed without prophylactic fasciotomies . \n\nfigure 4:complete arterial repair using an end - to - end reversed saphenous bridge .\nradial and ulnar pulses were regained directly postoperatively together with a normal color and warmth of the upper extremity , vascular observation was done to rule out compartment syndrome . in the postoperative period ,\nthe elbow was immobilized for 3 weeks with a posterior splint in 70 flexion , then active range of motion exercises was started . at 1-year follow - up ,\npatient regained all activities , and had nearly full range of motion , but with 15 loss of extension .\nthe frequency of vascular involvement associated with closed elbow dislocation remains difficult to establish because the literature only reports short series of sporadic case studies , it approaches 4.3% , and in some series , as low as 0.47% reported by spark et al . who had 3 cases of vascular injury out of 634 closed elbow dislocation .\nwhile reviewing the literature , we found only one case of brachial artery injury that was reported in the middle east and was treated conservatively .\nthis leads us to the fact that these types of injuries are either missed because of collateral circulation or underreported due to the lack of research and proper documentations .\nwhenever there is a suspicion of arterial damage , angiogram should be performed immediately and it still considered the gold standard for evaluation of arterial injury . sparks et al . \nreported that only 12 of 30 cases of closed dislocation investigated for arterial insufficiency by angiography had arterial injuries .\nhaving a positive pulses do not rule out brachial artery injury as patient can have a well - developed collateral circulation around the elbow . in our case ,\npatient first had a weak pulse , then it became absent , and this could be explained by two theories .\nfirst , an intact collateral circulation perfusing the radial and ulnar arteries and with ongoing elbow swelling , these collaterals were gradually compromised leading to impaired blood flow , and fading of the pulses .\nsecondly , it can be explained by the fact that the initial injury caused only an intimal injury , that was not sufficient to cause a complete brachial artery occlusion , but an ongoing thrombosis formation on top of the intimal injury was occluding it gradually .\nalthough radiograph with lateral view of the elbow shows clearly a dislocation when present , most of the spontaneous reduction can be misleading and the injury will be overlooked .\nonly two cases of occult elbow dislocation with vascular injury were reported in the literature , and in both cases , there was a complete rupture of the brachial artery .\nfew are the cases of intimal injury associated with elbow dislocation causing acute limb ischemia , in comparison with complete arterial transection ; due to the rarity of the condition , few are the articles showing the prevalence of this type of arterial injury . concerning the management , it is now generally accepted that the standard of care is repair or reconstruction of a brachial artery injury .\nto our knowledge , the combination of occult elbow dislocation with intimal injury of the brachial artery in a 71-year - old male makes this case to be the first reported in the literature . in conclusion , palpable pulses after elbow dislocation should not rule out arterial injury and arteriogram should be done in case of suspicion of vascular injury as it is the gold standard of diagnosis in these injuries .\nnormal radiographs as they show only the position of the joint at the time the radiographs was taken , and not the time of injury .\nif the clinical picture is in out of proportion with the x - ray findings , the case should be dealt with caution , and further investigations should be done .", "answer": "posterior elbow dislocation with vascular injury is rarely encountered , but it is crucial for every emergency physician to diagnose it . \n missing these injuries can result in neurovascular compromise , which in turn can lead to limb ischemia , compartment syndrome and potential limb loss . \n having a normal x - ray on presentation makes this injury more difficult to diagnose . in this study , we present a case of occult posterior elbow dislocation with an intimal injury of the brachial artery . \n the rarity of these cases , the diagnostic modalities and the treatment options will be reviewed .", "id": 447} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nNucleophilic Aromatic Substitution, A Guided Inquiry Laboratory Experiment\n\nPaper sections:\nIntroduction\n\"How to extract knowledge from experimental results is at the heart of science, yet for the most part we don't attempt to teach this skill in traditional labs [1].\" Recently, there has been significant interest in addressing this missing element in the curriculum. Inquiry-based laboratory experiments are a form of active learning that has the potential to enhance the student's critical thinking and analytical skills. We have applied this pedagogical concept to a traditional organic reaction, the N-arylation of aniline derivatives. The reaction is a practical way to introduce nucleophilic aromatic substitution into the undergraduate organic chemistry laboratory. There is also an expectation that the experiment will encourage students to see the connection between concepts and will give them the opportunity to constructively challenge what they know. Providing such an opportunity for reflection will enhance the intellectual climate of the organic chemistry course.
Often, the topic of nucleophilic aromatic substitution is presented with primary emphasis on the benzyne mechanism (Scheme 1), but with less discussion than is given to electrophilic aromatic substitution. Under the framework of inquiry-based learning, a straightforward laboratory procedure has been developed that focuses on the addition-elimination mechanism, Scheme 2. The experiment can be presented as an exploration of the trends in reactivity for the electrophile. Students are encouraged to draw upon their fundamental knowledge of chemical bonds and use that information to develop conclusions relating to the kinetic characteristics of the reaction. By doing so, students apply previously learned lecture concepts (i.e. resonance effects, nucleophilicity, leaving group trends, characteristics of polar covalent bonds, etc.) to the interpretation of laboratory results. In addition to promoting critical thinking, the experiment incorporates techniques such as acid/base extraction, microwave assisted organic synthesis (MAOS), TLC, HPLC, and IR.
The results obtained in this experiment differ from what students will expect for leaving group ability; but, the results do coincide with what is understood for polar covalent bonds. This provides an opportunity for the students to develop new knowledge through the logical and constructive discussion of results. Therefore, the experiment will reinforce useful laboratory techniques and instrumental methods while exposing the students to critical thinking in the analysis of data.
The preparation of (2-nitrophenyl)arylamines (3) has been well-studied utilizing traditional heating methods and organometallic reagents [2\u20135]. Nevertheless, many of these reactions require long reaction times and tedious extractions while producing only modest yields [3, 6]. The recent emergence of microwave assisted organic synthesis (MAOS) has created new opportunities for improving reaction conditions and outcomes. One such procedure has been adapted for the N-arylation of an aniline derivative. The reaction utilizes stoichiometric equivalents and is conducted under microwave irradiation, Scheme 3. The MAOS procedure employs an inexpensive basic clay (KF/K2CO3 in the reaction shown) to generate heat in the reaction, which proceeds without the use of solvents or organometallic reagents. Often, the procedure results in the complete conversion of the starting material to product.
\n\nOverview of the Experiment\nThe N-arylation of toluidine is used to represent the nucleophilic aromatic substitution. Since the reaction can be completed in less than 15 minutes, there is sufficient time for the extraction and the HPLC analysis of the reaction outcome in one class period. Therefore, the procedure was adapted to create a facile undergraduate laboratory experiment that is safe and can be repeated in the same laboratory setting if necessary. Our modified procedure does not give complete conversion of starting material to product. However, TLC of the final reaction mixture shows that only starting compounds (1 and 2) and the desired product (3) are present. When this mixture is washed with a 10% solution of HCl, the TLC shows that only the substituted nitrobenzene (1) and the product (3) are present in the organic layer. Subsequently, the mixture is analyzed by HPLC. If an HPLC is not available, the experiment can be conducted over two lab periods to allow the isolation of the product by column chromatography.
\n\n\nConsider what is known about polar covalent bonds. How does the electronegativity affect bond strength? Is this knowledge consistent with your results?
Based on your results and your answer to question 1, what is the connection between bond strength and leaving group ability?
What is the relative trend of leaving group ability in SNAr reaction?
What is the effect of electronegativity of the leaving group on the reactivity of the electrophile?
How does the electronegativity of the leaving group affect the ability of the reaction to take place?
\n\nOverview of the Experiment\nThe questions are purposely interrelated and model for the students how the results should be interpreted at various levels of inquiry. Collectively with the mechanism, the interpreted HPLC results aid the students in discussing how the electronegativity of the leaving group affects the rate of the reaction.
\n\nProcedure\nThe aniline derivative (0.25 g, 1 equiv) along with potassium fluoride (1 equiv) and potassium carbonate (1 equiv) are made into a powder using a mortar and pestle. The mixture is transferred to a vial. 2-fluoronitrobenzene (1 equiv; 1a\u2013c) is added to the mixture and thoroughly mixed with a glass rod. Then the mixture is placed in the microwave (CEM MSP 1000, 100W, 160 \u00b0C) for 10 minutes [7]. The mixture is allowed to cool for 10 min. Water (10-mL) is added and the mixture is extracted into ethyl acetate (3 \u00d7 15-mL). The ethyl acetate solution is then washed with a solution of 10% HCl followed by a solution of saturated Na2CO3. The organic layer is dried over anhydrous sodium sulfate and analyzed by HPLC to determine the relative yield of the reaction (ration of starting material to product present in the mixture). The TLC analysis of the ethyl acetate layer is conducted utilizing silica plates with UV indication and 20% ethyl acetate/80% hexane as the developing solvent.
\n\nDiscussion\nSuccessful completion of the experiment using 2-halo substituted nitrobenzenes illustrated the following trend in increasing leaving group ability: Cl < Br < F. Since electrophilicity can be directly related to leaving group ability, it can be observed in this experiment that by using the fluoro substituted nitrobenzene the reactivity of the electrophile will be increased. Based on this, the experiment indirectly illustrates how the electronegativity of the leaving group affects bond strength (the highest reaction yields are obtained when the bond between the leaving group and the ring is weakest). The results of the reaction can lead to further discussion relating to the polarization of bonds, aromaticity, and inductive effects.
\n\nConclusion\nWe have developed a microwave procedure that is a good illustration of the reaction between the aryl halide and the aniline derivative. The nucleophilic aromatic substitution reaction gives results that can be used to guide students understanding of basic organic trends surrounding the reaction. The newly developed laboratory module will contribute to the growing collection of inquiry-based activities that are available for organic chemistry. This procedure can be modified to include experiments relating to the reactivity of the nucleophile that will also be suitable for the undergraduate curriculum. In addition, the experiment reinforces key skills and instrumental techniques (TLC, HPLC, acid/base extraction). With the additional points of inquiry, the experiment would be excellent for use as a standalone experiment or capstone project.
\n\n\nList of possible electrophiles
", "answer": "Inquiry-based learning is a unique student-centered alternative to traditional instruction. This form of active learning is ideal for the organic chemistry laboratory as it encourages critical thinking and hands on problem solving to complete an experiment. Electrophilic Aromatic Substitution is immediately associated with the undergraduate organic chemistry course. However, nucleophilic aromatic substitution is not. The N-arylation of aniline derivatives is a useful reaction for implementing nucleophilic aromatic substitution into the undergraduate curriculum. Under the framework of inquiry-based learning, a straightforward procedure has been developed for the undergraduate laboratory. This experiment explores the reaction rate of the nucleophilic aromatic substitution using various electrophiles. The reaction is conducted under microwave irradiation and the experiment is completed in one laboratory setting.", "id": 448} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe roots of zapoteca portricensis is a common remedy in the treatment gastrointestinal disorders used by tradomedical practitioners in eastern nigeria .\nthis study was aimed at evaluating the possible antiulcer activity of the root of this plant in experimental rats .\ndifferent groups of albino rats of male sex were given three doses ( 50 , 100 , 200 mg / kg ) of the extract .\nthe ethanol model produced an average ulceration in rats with reduction of ulcer ( 50% , 75% and 90% ) seen in all the extract treatment .\na dose dependent inhibition of ulcer was seen in all doses of the extract with doses 100 and 200 mg / kg produced a significant reduction compared with control . in the indomethacin model ,\ninhibition of ulcer ( 57.1% , 65.7% and 80.0% ) was seen in the treatments with the extracts in a dose dependent manner .\nthis study has shown that roots of this plant ( zapoteca portoricensis ) possess potent antiulcer activity .", "answer": "background : the roots of zapoteca portricensis is a common remedy in the treatment gastrointestinal disorders used by tradomedical practitioners in eastern nigeria.aim:this study was aimed at evaluating the possible antiulcer activity of the root of this plant in experimental rats.methods:a methanolic root extract was prepared by cold maceration . \n antiulcer activity was tested using absolute ethanol and indomethacin induced ulcer models . \n sucralfate ( 100 mg / kg oral ) was used as the reference drug . \n different groups of albino rats of male sex were given three doses ( 50 , 100 , 200 mg / kg ) of the extract . \n phytochemical analysis of the freshly dried roots was also done.results:phytochemical results revealed presence of alkaloids , terpenoids , glycosides and flavonoids . \n the ethanol model produced an average ulceration in rats with reduction of ulcer ( 50% , 75% and 90% ) seen in all the extract treatment . \n a dose dependent inhibition of ulcer was seen in all doses of the extract with doses 100 and 200 mg / kg produced a significant reduction compared with control . in the indomethacin model , \n an absolute ulceration was produced in all the animals . \n inhibition of ulcer ( 57.1% , 65.7% and 80.0% ) was seen in the treatments with the extracts in a dose dependent manner . \n all the three doses of the extracts produced significant ulcer protection compared with control.conclusion:this study has shown that roots of this plant ( zapoteca portoricensis ) possess potent antiulcer activity .", "id": 449} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nCaryophyllene as a precursor of cross-linked materials\n\nPaper sections:\nIntroduction\nNew strategies to develop materials from renewable feedstock have been continuously sought as greener alternatives to commercial oil-based materials. There is a significant interest in polymeric materials, taking into consideration their wide range of applications, especially for elastomers. The elastomers market has witnessed significant growth in the global production in recent years, with an estimated increase in revenue from current US$ 80.73 billion to close to US$ 104.17 billion by 2026. 1,2 The adoption of vulcanized thermoplastics (TPV) in various application sectors has led to this development.
Among several categories of thermoplastics, the natural rubbers (NR) emerge as a major players. The NR segment plays an important role in the TPV global market since the NR is one of the most used thermoplastic thanks to their versatility. 2 Due to their properties such as high thermal stability, good chemical resistance, high tensile strength, low shrinkage, and greater design flexibility, they can be employed as devices and/or tools for automotive, medical, consumer goods, industrial, and other applications. 3,4 In the framework of looking for an alternative to oil-based consumer goods, an important number of research groups have concentrated their studies and described the synthesis of vegetable-oil-based thermoplastics, such as polyester, polyurethanes, polyamides, and many other bio-based polymers. [4][5][6][7][8][9][10] Terpenes and terpenoides have drawn considerable attention as potential starting precursors in the synthesis of elastomers. [11][12][13][14][15][16][17] Studies on the synthesis of elastomers from pinene, myrcene, and limonene [18][19][20][21] can be readily found in the scientific literature and some commercially available resins and adhesives (e.g. Piccolyte\u00ae) derived from polypinenes are already reported. However, there is little exploitation of sesquiterpenes by the scientific community. Among molecules defined as sesquiterpenes, caryophyllene and humulene stand out, since these molecules are made of interesting structural elements. These molecules are found in many essential oils such as rosemary, cannabis sativa, hops, and mostly clove oil. [22][23][24] The cheapest and most abundant sesquiterpene, the caryophyllene, is a versatile and significant molecule due to a bicyclic and a cyclobutane rings as well as unsaturated bonds present in its chemical structure. 23 Thanks to them, the caryophyllene can be easily modified by attaching different moieties to its backbone chain. Moreover caryophyllene is, to the best of our knowledge, the only readily available bio-based molecule that can be polymerized by ring-opening metathesis polymerization (ROMP) leading to polycaryophyllene (PCar). 25 PCar exhibits two carbon-carbon double bonds in its structure which can be further used to cross-link it.
Keeping in mind this context, the present research has aimed to the cross-linking of polycaryophyllene by using different routes and investigating the thermo-mechanical properties of the newly produced cross-linked bio-based elastomer. Two main pathways have been considered to reach three dimensional cross-linked polycaryophyllene: i) thermal pathways: in the presence of organic peroxides [benzoyl peroxide (BPO) or dicumyl peroxide (DCP)], or by classical vulcanization based on sulfur (SS) and ii) via UV light initiated thiol-click reactions at room temperature (see diagram in Fig. 1). As far as we know, this is the first study about the cross-linking of polycaryophyllene. To confirm the crosslinking, the gel fractions were quantified by extraction in THF at 50 \u00b0C for 48 hours.
The resulted gel fractions were 65 %, 90 %, and 72% for BPO, DCP, and SS respectively, as summarized in Table 1. The gel fraction appears to be limited for BPO cross-linking at 65% since even an increase of the curing temperature to 180 \u00b0C does not improve the gel fraction (see Table S1).
Obtaining a higher amount of gel fraction with DCP compared to with BPO was already identified in other studies. 26,27 Indeed, DCP is the most frequently used cross-linking agent since it is an organic peroxide which is more selective to vinyl moieties than benzoyl peroxide. 28,29 The ability of cumyloxy radical from DCP to react with non-activated vinyl moieties in a free-radical cross-linking pathway via H abstraction may be a possible explanation of its higher reactivity compared to BPO. 30 Additionally, the cumyloxy radical can undergo \u03b2-scission resulting in radical fragments (methyl radical and acetophenone) with high mobility. 31 Furthermore, the unsaturated bonds are not easily accessible by benzoyloxy radicals due to the steric hindrance around double bonds as the increase of formation of cross-linked networks. 24 The SEC analysis of the BPO soluble fraction testified to the presence of oligomers (see Fig. S7, Mn=320 g.mol -1 , \u0110=1.5) which indicated that some polymer backbone cleavage also takes place during the crosslinking. In the case of the sulfur system, the soluble fraction is mainly constituted of the accelerator and the catalyst used. Finally, the IR analysis of the materials obtained (see Fig. S8) shows that whatever the cross-linker, the vibration characteristics the carbon-carbon double bond (i.e. =CH2 bending 887 cm -1 , C=C stretching at 1645 cm -1 , C-H stretching at 3115 cm -1 ) are still present indicating a crosslinking by hydrogen abstraction mechanisms.
In order to confirm the occurrence of cross-linking reactions, on-line rheology measurements were carried out, they are shown in Fig. 2. The visco-elastic analysis also provided an estimation of the initial temperature of the cross-linking process. As expected, polycaryophyllene in the absence of a crosslinker behaves as a liquid for temperatures up to 160\u00b0C with the loss modulus (G'') higher than the storage modulus (G'). Classically, as the temperature increases, both moduli continuously decrease and no cross-linking reaction takes place at 160\u00b0C since no change in moduli was observed over time.
In the presence of DCP, a shoot up in moduli is clearly observed with a gel point (intersection point) at After the gel point, both loss and storage moduli reached constant plateaus and no more significant changes are observed. The magnitude of storage modulus increased up to 0.6, 0.5, and 0.5 kPa and the loss modulus to 1.2 MPa, 40, and 60 kPa respectively for polycaryophyllenes cross-linked by DCP, BPO, and sulfur system.
Concerning the UV cross-linking by thiol-ene coupling, the soluble fraction remains between 0% and 11% depending of the dithiol used (see Table 1). Interestingly, when the crosslinking is performed with 0.5 eq. of thiol per carbon-carbon double bond (db), a slight improvement of the gel fraction is observed (see Table S2). This may be to the presence of free dithiol in the soluble fraction. IR analysis of the polycaryophyllene obtained with 0.5 eq. of thiol per db shows no regioselectivity of the thiol-ene addition since the bands which are characteristic of the two carbon-carbon double bonds decrease (see Fig. S13).
For 1 eq. of thiol per db, double bonds appear to have totally disappeared whatever the dithiols used (see Fig. S14).
To obtain further information about cross-linked polycaryophyllenes, TGA and DSC measurements were performed in order to investigate their thermal properties, as shown in Fig. 3, Fig. 4 and Table 1. The mechanical properties of cross-linked polycaryophyllene were evaluated by dynamic mechanical analyses (DMA), displayed in Fig. 5 and Fig. S18.
The DMA curves show a typical behavior for cross-linked materials with a glassy plateau before the alpha transition temperature (T\uf061) followed by a rubbery zone after this point. in agreement with the one obtained by DSC (12 \u00b0C, -6 \u00b0C and -9 \u00b0C respectively). Finally, the rubbery plateau confirms the cross-linking of the materials and its value is directly proportional to the cross-linking density. Polycaryophyllene crosslinked by DCP exhibits significantly higher storage modulus above glass transition temperature (27 MPa) compared to SS or BPO systems (0.7 and 0.9 MPa respectively) (see Table 1) or even DDT cross-linking (4.6 MPa).
\n\nConclusions\nIn the present work, caryophyllene was polymerized by ROMP and the polymer obtained was crosslinked using different routes: organic peroxides, sulfur system or dithiol. Rheological analyses confirmed the occurrence of cross-linking reactions in agreement with the extractions by THF results. Swelling experiments showed that the polycaryophyllene was entirely cross-linked by DCP or dithiols with an insoluble fraction over 90%. Cross-linking by sulfur system resulted in a gel content of 72%.
The cross-linked materials were in-depth analyzed by TGA, DSC and DMA. Materials were obtained with Tg between -22\u00b0C and 12\u00b0C with improved thermal stability compared to non-cross-linked polycaryophyllene (T10% > 300\u00b0C). At room temperature (20\u00b0C) storage modulus of the cross-linked polycaryophyllene were between 1 MPa to 100 MPa. Based on the achieved results, they could potentially find applications as replacement of synthetic rubbers.
", "answer": "This paper aims at the synthesis of a new type of elastomers from caryophyllene. The adopted strategy was to cross-link the polycaryophyllene, which was synthesized by ring-opening metathesis polymerization (ROMP). The polycaryophyllene obtained showed Mn = 2 x 10 4 g.mol -1 (\u0110 = 1.5) with a glass transition temperature (Tg) of -35 \u00b0C. On the first hand, thermal crosslinking was performed in the presence of organic peroxides or sulfur system. On the second hand, thiol-ene coupling initiated by UVlight at room temperature was also investigated as an alternative pathway to cross-link the polycaryophyllene. The materials obtained were analyzed by TGA, DSC, and DMA. The Tg of cross-linked polycaryophyllene could be easily modulated from -35 \u00b0C to a range between -25 and 10 \u00b0C by changing the type of cross-linking agent. The curing process led to the improvement of thermal stability ranging from 200 \u00b0C to around 340 \u00b0C. Finally, the network storage modulus varied from 1 to 100 MPa at room temperature.", "id": 450} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe collected all possible literature from the year 1972 ( when kfd was first described ) to the present day conducting a medical search on kikuchi fujimoto disease ( kfd ) in english language .\nwe included publications in authorized medical journals including original and review articles / theses , editorials , case reports and brief communications .\nkfd is an extremely uncommon disease but cosmopolitan with higher japanese and asiatic prevalence.1,2 however , sporadic cases have also been reported from europe . in asian woman\nkikuchi s disease is rare and benign cause of cervical lymphadenopathy.3 the disease , most often , happens to occur in young adults below 40 and seldom in children.4 at first , little female predominance was considered , but the recent literature regards it as male to female ratio 1:1.1,5 a current study on the patients with kfd conducted in taiwan reports the average age of 21.5 cardiac , hepatic and pulmonary involvement raises the morbidity .\nhowever , role of viruses ( epstein - barr virus and others ) in the pathogenesis of kikuchi s disease is controversial and unremarked.1 on the other hand , unger and coworkers are in favor of viral etiology as kfd manifests certain viral features ie , atypical lymphocytosis , certain histologic features , flulike respiratory prodrome and no response to antibiotic therapy.7 also , kikuchi s disease has been reported in patients with aids.8 like systemic lupus erythematosus ( sle ) , lymphocytes and histiocytes in the patients with kikuchi s disease show tubular reticular structures in their cytoplasm on electron microscopy.9 it has been opinioned that in genetically susceptible individuals , kfd may belong to exuberant t - cell mediated immune response provoked by variety of stimuli.1 even though course of cell death in kfd needs to be studied and emphasized , ohshima and his associates remarked apoptotic cell death might be involved in the pathogenesis of kfd.10 regarding to this study , proliferating cd8 t - cells may kill or be killed in the apoptotic process of this disease using fas and perforine pathways .\nkikuchi s disease begins as an acute or sub - acute condition , developing over two to three week period .\ntender cervical lymphadenopathy is the characteristic feature ( 56%98% ) of kfd , predominantly involving the posterior cervical triangle .\nsize of the enlarged lymph nodes ranges from 0.5 cm to 4 cm ( occasionally 6 cm ) .\n59% patients represent painful lymphadenopathy and 1%22% patients undergo generalized lymphadenopathy.4,7,9,11 kfd , more or less , rarely involves mediastinal , peritoneal or retroperitoneal regions of the body.2 fever ( 30%50% ) associated with upper respiratory symptoms , sore throat , night sweats , weight loss , headache , rash , nausea , vomiting , and leukopenia ( about 50% ) are the other manifestations of the disease .\n12,13 atypical lymphocytes have been reported in the peripheral blood film of patients with kfd .\nextranodal involvement is rare ; however , skin , eye and bone marrow affection has been reported.1 nevertheless , kfd is linked to sle and autoimmune conditions as lymphocytes and histiocytes in the patients with kikuchi s disease show tubular reticular structures in their cytoplasm on electron microscopy.1,14 additionally , extranodal involvement in kfd is associated with frequent systemic symptoms .\nanecdotal reports bring to light the unusual features of kfd like haemophagocytic syndrome and carcinoma15 along with fatal multicentric disease .\nnervous system involvement ( septic meningitis , acute cerebellar ataxia , and encephalitis ) rarely happens to occur.16 regarding joint involvement , a case of 14 year old boy with kfd is in the record.17\nin patients with kikuchi fujimoto disease , an excisional biopsy of the involved lymph nodes is the investigation of choice .\ncoagulative necrosis with ample karyorrhetic debris in paracortical areas of the involved lymph nodes is the characteristic histologic feature of kfd .\nother baseline investigations are reported unaffected . nevertheless , laboratory results of some kfd cases have reported anemia , little rise in esr and even leukopenia .\none third individuals with kfd have shown atypical lymphocytes in their peripheral blood films.5 predominantly , t - cells ( cd8 + t - cells ) are found in kfd .\nhowever , neutrophils are found absent and scarce plasma cells may or may not be present . according to kuo\n, histopathologic features can be classified in three stages : proliferative , necrotizing , and xanthomatous.18 proliferative stage expresses various histiocytes , plasmacytoid monocytes and lymphoid cells containing karyorrhetic nuclear fragments , and eosinophilic apoptotic debris .\nnecrotizing stage shows a degree of coagulative necrosis while xanthomatous stage is predominantly stuffed with foamy histiocytes .\nit must be born in mind that in the individuals with kfd , atypical reactive immunoblastic component is common and can be mistaken for lymphoma.4 histiocyte - associated antigens ( lysozyme , myeloperoxidase and cd68 ) are also expressed by histiocytes in kfd .\nkfd is an extremely rare disease and the differential diagnosis can be established on the basis of enlarged lymph nodes which are associated with many other disorders .\nit is necessary to born in mind the differential diagnosis of kfd as its treatment dramatically differs from other disorders .\nlymphoma ( non - hodgkin s lymphoma ) , tuberculosis , sle , plasmacytoid t - cell leukemia , kawasaki s disease , and myeloid tumor are included in the differential diagnosis of kfd.1 sometimes , because of similar clinical and histological features , it becomes problematic to differentiate kikuchi fujimoto disease from lymphadenitis associated with systemic lupus erythematosus ( sle ) .\nhowever , it has been reported that kfd is associated with sle . in order to exclude sle ,\nall the necessary investigations of sle ( c3 , c4 , anf , anti - sm , and le cells ) are required .\nearly recognition of kikuchi fujimoto disease is of prime importance to save the patient from undergoing extensive investigations related to malignant lymphoma and other related disorders.8 histopathologic features like presence of abundant reactive histiocytes and absence of reed - sternberg cells favor kfd .\nsometimes , kfd may express histiocytes resembling with signet - ring cells and can be confused with signet - ring carcinoma .\nhowever , metastaic adenocarcinoma contains cells with atypical nuclei and mucin debris instead of cellular debris .\nkikuchi fujimoto disease ( histiocytic necrotizing lymhadenitis ) is a self - limiting condition that resolves spontaneously within 1 to 4 months of period .\nhowever , studies reveal recurrence of the disease in 3%4% of the patients.9 additionally , sle may happen to occur some years later .\nno hereditary risk has been documented in kfd.8 most of the time symptomatic relief is offered for the local and systemic complains of the disease .\nlymph node tenderness and fever is treated with analgesics , antipyretics , and nsaids . sometimes , but rarely , steroids can be used temporarily , especially in severe extranodal involvement or generalized clinical course.19 in order to run an excisional biopsy of the enlarged lymph nodes , surgical consultation may be prerequisite .\nindividuals with kikuchi fujimoto disease should be examined systemically and they must be under regular follow - up in order to monitor the manifestations of sle . the course of cervical lymphadenopathy is benign and resolves spontaneously .\nvery few cases have been reported as fatal . however , no standard or specific treatment of kfd has been recommended .\nkikuchi fujimoto disease is an idiopathic , extremely rare , more or less worldwide , and often under - diagnosed condition ; predominantly involving the posterior cervical lymph nodes .\nearly recognition of kikuchi s disease is of prime importance to avoid extensive and expensive investigations related to malignant lymphoma other related disorders . in order to avoid misdiagnosis , awareness of this disease", "answer": "in order to determine the clinical significance of kikuchi fujimoto disease ( histiocytic necrotizing lymhadenitis ) and to review the literature available on this condition , we selected the medicine research papers in english language published between the years 1972 to 2011.kikuchi fujimoto disease ( kfd ) is an uncommon , cosmopolitan , benign and self - limiting condition with higher japanese and asian prevalence . \n most of the sufferers of kfd are young people who seek treatment because of having acute tender cervical lymphadenopathy , low grade fever and night sweats . \n coagulative necrosis with ample karyorrhetic debris in paracortical areas of the involved lymph nodes is the characteristic histologic feature of kfd . \n diagnosing kfd is crucial as it can be mistaken for malignant lymphoma and sle.kfd was put forth first time in 1972 by dr . \n masahiro kikuchi and by funimoto as lymphadenitis with reticular proliferation , histiocytes and abundant nuclear debris . \n it is a rare benign condition of lymph nodes and most of the clinicians and pathologists are unfamiliar with it . \n kfd is self - limiting disease ( within 1 to 4 months ) , however , patients should be followed up regularly as it may crop up again or progress to sle . \n analgesics and antipyretics help to ameliorate the symptoms .", "id": 451} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 41-year - old woman prompted a visit to an optometrist due to blurred vision in june 2013 , and was diagnosed to have retinal hemorrhage .\ncomplete blood count revealed marked leukocytosis ( 326 k/l ) , neutrophilia ( 25% , 64.6 k/l ) with a prominent myelocyte peak ( 27.5% myelocytes ) , basophilia ( 4.0% , 12.9 k/l ) , and mild normocytic anemia ( hemoglobin 10.4 g / dl ) .\nbone marrow study revealed hyperplastic myeloid series ( myeloid / erythroid ratio of 8.1/1 ) with only 1.2% blasts .\nfurther both karyotype and fish analysis revealed presence of philadelphia chromosome in nearly all cells ( fig .\n1a and b ) based on these findings patient was diagnosed with chronic myeloid leukemia ( cml ) , chronic phase .\nshe was started on imatinib 400 mg daily and hydroxyurea . despite achieving hematological remission three months after diagnosis ,\npatient continued to have persistent cytogenetic disease as detected on follow up fish assays with 32% cells showing t ( 9 ; 22 ) . in june 2014 , patient was switched to nilotinib , as she appeared to have imatinib resistant disease , although molecular testing for abl kinase mutational analysis was negative . in july 2015\ncbc done at that time revealed a normal white cell count of 9.1 k/l with 17.5% circulating blasts , ( fig .\n1c ) and hemoglobin of 7.5 g / dl . bone marrow aspiration and biopsy was performed and the specimen was also submitted for flow cytometry and cytogenetic analysis .\nprominent erythroid hyperplasia was noted on the bone marrow aspirate smears with 69.5% erythroid precursors , several of which showed dysplastic features ( fig .\nalthough only 9% blasts were counted on the bone marrow differential count , flow cytometry revealed 14% cells in the blast gate ( fig .\n1 g ) mostly expressing myeloid markers cd117 , cd33 , stem cell marker cd34 and with partial aberrant expression of lymphoid marker cd7 .\nalthough no solid sheets of blasts were seen , cd34 highlighted scattered blasts throughout the biopsy section with a variable distribution estimated at approximately 1015% ( fig .\nbased on the presence of marked erythroid hyperplasia ( 69.5% ) and 9% bone marrow blasts the diagnostic criteria for acute erythroid / myeloid leukemia were met and a diagnosis of blast transformation of underlying cml to acute erythroid / myeloid leukemia was made .\npatient received 7 + 3 induction chemotherapy with idarubicin and cytoxan . despite lowering of her\nshe further developed subarachnoid hemorrhage , and septicemia and subsequently died six weeks after her hospitalization .\nchronic myelogenous leukemia ( cml ) is a clonal disorder involving the pluripotent stem cell and is consistently associated with the bcr - abl1 fusion gene located on the philadelphia chromosome .\nthe disease typically evolves in 3 distinct clinical stages : chronic and accelerated phases and blast crisis . in approximately 70% of cases ,\nthe blast lineage is myeloid , of which granulocytic and monocytic blasts are more common .\nerythroid blast phase of cml is relatively rare and a literature review suggests that the incidence ranges from 0% to 10% .\nacute erythroid leukemia is a rare subtype ( < 5% ) of acute myeloid leukemia that may arise de novo or from transformation of an underlying myelodysplastic syndrome .\nit is further subdivided into two subtypes namely : acute erythroleukemia and pure erythroid leukemia .\nunlike pure erythroid leukemia in which the erythroid series is mostly comprised of proerythroblasts and basophilic erythroblasts , in acute erythroleukemia ( erythroid / myeloid ) all maturation stages of the erythroid precursors are present ( comprise > 50% of the entire nucleated cell population ) , may frequently show a shift to immaturity , are dyspoietic and myeloblasts comprise greater than 20% of non - erythroid cells .\nchronic myelogenous leukemia with erythroid crisis is a rare entity with variable reported incidence rates .\nbased on our review of literature we came across very few reported cases of transformation of underlying cml to acute erythroid leukemia , , , , , .\nwe also searched our institutional database for all cases of cml that transformed to acute leukemia over the course of last twenty years and did not find any other cml patient with erythroid blast crisis . whether the criteria listed for diagnosis of erythroleukemia should be applied in cml erythroid blast phase is poorly defined .\nsome studies have considered the percentage of normoblasts below 50% as criteria for erythroblast phase but not erythroleukemia .\nalthough acute erythroid leukemia is far less common than cml erythroblast crisis , a few cases of philadelphia - positive acute erythroid leukemia have been reported .\nstudies have also suggested that erythroid blast phase is not independent of cml chronic phase .\nbcr - abl fusion product in the normoblasts of cml , which provides concrete evidence confirming erythroid leukemia rather than a hyperplastic process . in our case at the time of disease progression in 2015 we were able to demonstrate presence of both bcr - abl fusion and monosomy 7 in majority of the bone marrow cells that on morphology were mostly erythroid precursors by fish assays . although the 9 ; 22 translocation was seen at the time of diagnosis , the anomalies of chromosome 7 and 3 were newly acquired in 2015 , indicating karyotype evolution and disease progression . in the blastic phase of cml ,\nseveral additional chromosome aberrations in addition to the philadelphia chromosome have been reported in 7580% of patients , , .\ncomplex rearrangements are widely dominant in acute erythroleukemia with clonal abnormalities mostly involving chromosomes 5 and 7 followed by 8 , 16 and 21 .\nph - positive acute erythroid leukemia represents an even less common occurrence than erythroid blast phase cml .\nit is difficult to distinguish the erythroblast phase of cml from a ph - positive acute leukemia .\nalthough complex karyotype and presence of multiple chromosomal abnormalities is fairly common in all cases of acute erythroleukemia , very few cases of ph - positive erythroleukemia have been reported .\nblast phase of cml is often associated with a complex karyotype , including trisomy 8 and 19 , double ph chromosomes , and isochromosome i ( 17q ) , . the who classification\ndoes not specifically address the issue of erythroid hyperplasia in patients with cml or erythroid blast phase of cml .\nwe feel due to presence of more than 50% erythroid precursors and increased myeloblasts ( greater than 20% of the non - erythroid cells ) our case meets the who diagnostic criteria for acute erythroleukemia ( erythroid / myeloid ) .\nthe criteria for diagnosing acute erythroleukemia arising from an underlying cml have not been firmly established , partly due to the rare occurrence of this phenomenon .\nchronic myelogenous leukemia blast crisis is highly refractory to standard induction chemotherapy , with a response rate of less than 2030% , . in\npatient 's with imatinib resistant disease dastanib and nilotinib can help achieve hematological response however neither drug has been reported to be entirely effective in achieving complete cytogenetic remission or for treatment of blast crisis .\nfurther acute erythroid leukemia has an aggressive clinical course mostly with an adverse clinical outcome .", "answer": "chronic myelogenous leukemia ( cml ) is a myeloproliferative disorder where over a period of time 1520% of patients show blastic transformation with majority transforming into acute myeloid leukemia , most of which are of granulocytic lineage . \n erythroid blast phase of cml is relatively rare with the incidence ranging from 010% . \n further the incidence of acute erythroid leukemia by itself is fairly low amongst all acute leukemias . \n we report a case of 41-year - old patient with cml who failed to achieve cytogenetic remission , transformed to acute erythroid leukemia and eventually succumbed to the disease over a short period of time . \n related literature is also reviewed", "id": 452} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\namyotrophic lateral sclerosis / parkinsonism - dementia complex ( als / pdc ) is a rare disorder endemic to guam island and the kii peninsula of japan .\nit shows a unique combination of parkinsonism , amyotrophy , and dementia , and the form of dementia , which shows a phenotype similar to alzheimer 's disease ( ad ) , is becoming predominant in the kii peninsula .\nalthough kii als / pdc shows several unique clinical features , including severe atrophy of the frontal and temporal lobes on magnetic resonance imaging ( mri ) , decreased cerebral blood flow in the frontal and temporal lobes on single - photon emission computed tomography ( spect ) , pigmentary retinopathy , and decreased cardiac i - meta - iodobenzylguanidine uptake , a postmortem examination is required for a definitive diagnosis . since biomarkers for als\n/ pdc have not yet been identified , we analyzed cerebrospinal fluid ( csf ) biomarkers for kii als / pdc to discriminate it from other neurodegenerative disorders .\nwe collected csf samples from 12 patients with kii als / pdc ( 6 men , 6 women , mean age 67.9 3.7 years , mean illness duration 5.63 years ) , nine patients with ad ( 2 men , 7 women , mean age 61.1 8.7 years , mean illness duration 1.92 years ) , 11 patients with als ( 8 men , 3 women , mean age 60.6 12.6 years , mean illness duration 1.1 years ) , nine patients with parkinson 's disease ( pd ; 7 men , 2 women , mean age 71.3 2.2 years , mean illness duration 4.42 years ) , and five disease control patients ( c ; 4 men , 1 woman , mean age 36.2 20.3 years ) .\nall of the patients with kii als / pdc were natives of hohara village , which is an area of high als / pdc prevalence on the kii peninsula .\nwe collected csf samples over 10 years ; therefore , the period between csf collection and analysis was not standardized .\nthe diagnosis of kii als was made according to the airlie house criteria , since the clinical symptoms of kii als are essentially the same as those of classical als .\nthe diagnosis of kii pdc was made by a unique combination of levodopa - unresponsive parkinsonism and dementia , which are frequently accompanied by amyotrophy of the extremities and/or pyramidal tract signs .\nmini - mental state examination ( mmse ) was used for the evaluation of dementia and cut - off point was 23 ( data not shown ) .\nthe frontal lobes and/or temporal lobes of als / pdc patients showed atrophy on mri and/or a decrease of cerebral blood flow on spect .\ncsf samples were immediately centrifuged at 1000 g for 15 min and stored at 80c with polypropylene tube .\nthe total tau ( t - tau ) , phosphorylated tau ( p - tau ) , and amyloid beta ( a ) concentrations were measured with an enzyme - linked immunosorbent assay ( elisa ) kit using a monoclonal antibody specific for t - tau , p - tau , and a142 ( innotest htau ag , phosphor tau(181p ) , and -amyloid ( 142 ) , innogenetics , ghent , belgium ) .\nelisa assays were carried out using several samples from each group on the same plate in a randomized manner and were repeated using randomized samples in the same manner in plural times .\na factorial anova was performed with csf - t - tau , csf - p - tau , and csf - a42 , as dependent variables , with the diagnostic category ( ad , als , c , kii als / pdc , and pd ) using jmp 9.0 .\nthe ethics committee of mie university graduate school of medicine approved this study and the declaration of helsinki was followed .\ncsf - a42 , csf - t - tau , and csf - p - tau were compared between ad , als , c , kii als / pdc , and pd .\nthe concentrations of csf - t - tau and csf - p - tau were significantly higher in ad ( t - tau ; 378.0 41.76 pg / ml ; p < 0.001 , p - tau ; 42.4 6.78 pg / ml ; p < 0.028 ) than in the other groups .\nhowever , the concentrations of csf - t - tau and csf - p - tau did not differ significantly between kii als / pdc , als , c , and pd ( figures 1(a ) and 1(b ) ) .\nthe concentration of csf - a42 was significantly reduced in ad ( 402.2 56.6 pg / ml ; p < 0.03 ) compared to als and c and relatively reduced in kii als / pdc ( 465.4 53.69 pg / ml ; p < 0.018 ) compared to als .\nmost of the als / pdc patients had csf concentration values that fell below the cutoff based on c ( figure 1(c ) ) .\nthe ratios of csf - p - tau to csf - a42 were significantly increased in ad ( 0.125 0.02 ) compared with kii als / pdc ( 0.043 0.02 ; p < 0.008 ) , als ( 0.035 0.019 ; p < 0.003 ) , pd ( 0.025 0.02 ; p < 0.002 ) , and c ( 0.027 0.09 ; p\nthe concentrations of csf - t - tau , csf - p - tau , or csf - a42 were not related to the clinical parameters ( age , sex , illness duration , or dementia ) in the kii als / pdc patients .\nthe number of c samples was small and the average age of control patients was low .\ngenerally , csf tau level gradually increase according to age and csf a is not affected by age .\ncsf tau level of c samples was relatively low , but it was not significant .\nthus , the csf values of c were not comparable to those of other groups .\nnevertheless , the optimal cut - off values that discriminate c from ad were similar to those in previous reports [ 6 , 7 ] in which a larger number of control samples were analyzed .\ncsf tau level of kii als / pdc samples did not increase , although the average age of kii als / pdc group was older than that of ad group .\nthe present study showed that csf - t - tau and csf - p - tau concentrations from patients with kii als / pdc were not increased compared to those in the other disease groups , and a42 concentration in the csf was relatively decreased .\nthe ratio of csf - p - tau to csf - a42 segregates kii als / pdc from ad .\nbecause als / pdc is associated with tau pathology in the absence of amyloid plaques , the expectation was that als / pdc patients would not show the alzheimer 's disease ( ad ) profile of decreased a42 but might show increased t - tau and/or p - tau in the csf .\nin general , decreased csf - a42 indicates plaque pathology , and increased csf - t - tau and csf - p - tau indicate axonal degeneration and tangle pathology , respectively .\nrecently , the average age of onset of kii als / pdc is increasing and a deposition is conspicuous in autopsied patients . therefore , decreased csf - a42 may reflect a pathology in the most recent patients .\nwe analyzed the precise tau isoform of over 10 patients with autopsy - proven als / pdc recently and identified a 3r + 4r type , 4r > 3r type , and a 4r predominant type .\nthe glial tau pathology is particularly related to the 4r isoform , and we consider kii als / pdc to be a 4r - dominant tauopathy ( unpublished data ) .\nnoguchi et al . examined the concentrations of csf - t - tau , csf - p - tau , and csf - a42 in patients with progressive supranuclear palsy ( psp ) and corticobasal degeneration ( cbd ) ; the concentrations of csf - t - tau and csf - p - tau did not significantly differ between psp , cbd , and controls , and the concentration of csf - a42 was significantly lower in psp and cbd than in controls .\nthe authors speculated that the absence of an increase of csf - t - tau and csf - p - tau concentrations might reflect 4r tau predominance and a reduction of csf - a42 might suggest deposition or mismetabolism of a . taken together , csf biomarkers of kii als / pdc might have similar properties to those of 4r tauopathy , psp , and cbd ; however the relationship between tau isoform and csf tau level remains to be resolved .\nfinally , the present findings , in which csf - t - tau and csf - p - tau concentrations were not increased and csf - a42 concentration was relatively decreased , suggest that csf analysis may be useful to differentiate als / pdc from ad , als , and pd . nevertheless there is a major limitation of the interpretation of the data .\nthe size of each group is small , the age of the control group is much younger , and there were two populations in the ad group regarding the levels tau , p - tau , and a/p - tau .\nfurther study using groups with larger size of subjects is needed to confirm the proposed utility of the csf biomarkers .", "answer": "objective . \n amyotrophic lateral sclerosis / parkinsonism - dementia complex is classified as one of the tauopathies . methods . \n the total tau , phosphorylated tau , and amyloid 42 levels were assayed in cerebrospinal fluid from patients with kii amyotrophic lateral sclerosis / parkinsonism - dementia complex ( n = 12 ) , alzheimer 's disease ( n = 9 ) , parkinson 's disease ( n = 9 ) , amyotrophic lateral sclerosis ( n = 11 ) , and controls ( n = 5 ) using specific enzyme - linked immunosorbent assay methods . results . \n total tau and phosphorylated tau did not increase and amyloid 42 was relatively reduced in kii amyotrophic lateral sclerosis / parkinsonism - dementia complex . \n relatively reduced amyloid 42 might discriminate kii amyotrophic lateral sclerosis / parkinsonism - dementia complex from amyotrophic lateral sclerosis and parkinson 's disease , and the ratios of phosphorylated - tau to amyloid 42 could discriminate kii amyotrophic lateral sclerosis / parkinsonism - dementia complex from alzheimer 's disease \n . conclusions . \n cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis / parkinsonism - dementia complex from alzheimer 's disease , amyotrophic lateral sclerosis , and parkinson 's disease .", "id": 453} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalthough decades have passed since most cellular organelles were initially characterized by microscopy and subcellular fractionation , a complete catalogue of the proteins in each organelle has yet to be obtained .\nwhereas genomics provides a list of potential proteins encoded by an organism 's genome , data from proteomic analysis can provide the ' rosetta stone ' that allows assignment of specific proteins to different subcellular structures .\nthe most informative proteomic analysis requires highly purified organelle ( sub)fractions , yet subcellular fractionation is notorious for cross - contamination .\ncomparative analysis of organellar subfractions can potentially circumvent this problem by providing a rational basis for distinguishing bona fide organelle components from contaminants . here , we scrutinize the use of such an approach to survey the integral membrane proteins of the nuclear envelope .\nthe nuclear envelope is a double - membrane system , continuous with the endoplasmic reticulum ( er ) , that encloses the nuclear contents ( figure 1 ) .\nit is perforated by nuclear pore complexes ( npcs ) , large supramolecular assemblies that mediate nucleo - cytoplasmic traffic . in higher eukaryotes ,\nthe nuclear envelope is lined by a protein meshwork , the nuclear lamina , which is an attachment site for npcs and chromatin .\nin contrast , the inner nuclear membrane ( inm ) contains a set of unique integral membrane proteins , many of which bind to lamins ( the predominant proteins of the nuclear lamina ) and/or to chromatin .\na quarter of a century of biochemical , cell biological , and genetic approaches has identified several integral inm proteins in higher eukaryotes , including lamin - b receptor ( lbr ) , lamina - associated polypeptides ( laps ) 1 and 2 , man1 , nurim , and emerin .\nmost of these proteins and several novel components have now been detected in a single proteomics study of nuclear envelopes .\nmany methods have been developed to isolate nuclear and nuclear - envelope fractions from eukaryotic cells .\nthese fractions are invariably contaminated by other cytoplasmic organelles and filaments , however . moreover ,\nthe close interactions between the npcs , nuclear lamina , inm and chromatin make it impossible to cleanly separate these components .\nproteomics , which couples mass - spectrometric analysis of proteins with mining of the protein databases derived from genomics , can potentially identify most proteins in a nuclear envelope fraction , but it can not distinguish nuclear envelope components from contaminants .\ndreger and colleagues used comparative proteomics of different nuclear envelope subfractions isolated from cultured neuroblastoma cells to identify integral proteins of the inm .\nthey took advantage of previous findings that the nuclear lamina is insoluble in both nonionic detergent and salt , and that many integral proteins of the inm remain associated with the lamina after detergent or salt extraction .\nthey therefore separated proteins from three different nuclear envelope subfractions on two - dimensional gels , excised protein spots from the gels , cleaved the proteins within each spot with protease , and analyzed the resulting peptides by maldi - tof ( matrix - assisted laser - desorption / ionization time - of - flight ) mass spectrometry . in one extraction ,\nnuclear envelopes were treated with the detergent triton x-100 to solubilize proteins of the outer nuclear membrane and er .\nthe triton x-100 pellet ( ' detergent - resistant ' in table 1 ) , which contains the nuclear lamina , is enriched in lamin - binding inm proteins .\na second pellet was obtained by salt extraction of nuclear envelopes ( ' salt - resistant ' ; table 1 ) and is expected to be similarly enriched in the lamina , but with different contaminants removed .\na third extraction involved treatment of nuclear envelopes with a urea / carbonate solution and yields a pellet ( ' chaotrope - resistant ' ; table 1 ) containing integral membrane proteins of the inm , outer nuclear membrane and er ( plus contaminating organelles ) . on the basis of the logic discussed above , integral membrane proteins ( chaotrope pellet ) that were also found in the detergent and salt pellets were good candidates for novel inm proteins .\nthis analysis identified most previously characterized inm proteins , as well as four novel integral proteins .\ntwo of the novel four were splice variants of the lamina - associated protein lap2 , previously observed only as mrnas .\nthe identification of unique peptides , including some that overlap predicted splice junctions between exons , confirmed the presence of three previously observed ( , , ) and two novel ( , ) lap2 isoforms .\nthe remaining two lap2 isoforms that had been identified as mrnas ( , ' ) were not observed ( although all lap2 isoforms contain chromatin and/or lamin - binding domains that predict their targeting to the nuclear envelope ) .\nlap2 , a splice variant lacking a transmembrane domain , was absent from the chaotrope - resistant fraction , supporting the logic of the comparative approach .\nthe third novel inm protein to be identified was a homolog of unc84a , a caenorhabditis elegans protein previously localized to the nuclear envelope .\nthe fourth protein , luma , was completely novel and includes no known domains and so has no predicted functions .\ndreger and colleagues did not detect lap1 , although it has been observed in a variety of mammalian cell types .\nthis could result from its loss during fractionation , its absence from the neuroblastoma line examined , or other technical problems ( for example , only about 75% of the protein spots seen on the two - dimensional gel yielded assignments by mass spectrometry ) .\nlow abundance is also a potential problem . whereas lamins are present at millions of copies per cell , previously characterized inm proteins are far less abundant . notwithstanding\nthe high sensitivity of mass spectrometry , minor proteins may go undetected . just as local dialect modifications can limit some translations using the rosetta stone , atypical protein behaviors can limit comparative proteomic approaches . each comparative approach is tailored by knowledge of the fractionation behavior of previously characterized components of an organelle .\nthus , in comparing the proteins appearing in the three nuclear envelope fractions , dreger and colleagues found that all well characterized intranuclear proteins were absent from the chaotrope - resistant fraction , and most known inm proteins were in all three fractions .\nemerin , which is known to bind lamins , was absent from the detergent - resistant fraction , and lbr , the sequence of which includes seven transmembrane segments , was detected only in the detergent - resistant fraction and not in the chaotrope- or salt - resistant fractions ( table 1 ) .\nthree of the novel proteins identified by the study were in all three fractions , but luma was absent from the salt - resistant fraction .\nthus , luma would have been missed if a requirement that novel inm proteins appear in all three fractions had been enforced .\natypical behavior of contaminants can also limit the effectiveness of comparative approaches . in the dreger study\n, some known proteins with clearly cytoplasmic localizations and functions also appeared in all three pellets , including mitochondrial proteins ( f1-atp - synthase ) and cytoskeletal ones ( actin and tubulin ) .\nthis underscores the need to complement the proteomic identification of new organellar components with other approaches , including direct localization .\nthus , to ensure that luma and the unc84a homolog were not contaminants , their cdnas were isolated , epitope - tagged , and transfected into cos7 cells , to confirm nuclear - envelope targeting .\nrout and colleagues , when analyzing the yeast npc by proteomics , used the additional criterion of enrichment with the npc to distinguish contaminants .\ncandidate proteins from an npc - enriched fraction were epitope - tagged at their genomic loci .\nonly when the majority of tagged protein was found to reside at the npc ( by immunogold electron microscopy , immunofluorescence microscopy , and co - fractionation with known npc proteins ) was it considered a true npc component .\nsome proteins have multiple cellular localizations , however , and this criterion eliminated , for example , the sec13 protein , which is involved in protein translocation across the er membrane yet has a second function at the npc .\neven with the four novel inm proteins demonstrated by the dreger study , we predict that many inm proteins remain to be discovered ; some of these could be amongst the 25% of protein spots that eluded analysis .\nfor example , unc84a appears in all c. elegans tissues , but unc83 , an inm protein that interacts with unc84a , appears in only a subset .\nnuclear envelope proteome analyses of different tissues may uncover a mammalian unc83 homolog and other tissue - specific inm proteins .\nindeed , a novel tissue - specific inm protein was just discovered . this protein , named myne-1 , binds lamins and appears specifically in myocytes .\napplying proteomics directly to complex protein mixtures , rather than restricting analysis to the proteins recovered from gels , should increase the number of proteins detected .\nmoreover , this method could estimate the relative amounts of different proteins in a subcellular compartment by determining the relative peptide quantities after protease cleavage .\npost - translationally modified peptides could be identified by comparing peptide profiles with or without treatments that remove the modifications ( for example , chemical removal of sugars ) ; and a combination of this type of approach with relative quantitation could provide information on the proportion of a protein in an organelle that is modified . by analysis of complex mixtures ,\nthe protein profiles of organelles in different functional states or extracted with different ionic strengths can be compared more comprehensively and rapidly than with classical approaches . in the past two years , organellar proteomics\nhas also profiled mitochondrial , chloroplast , and nucleolar proteomes , uncovered minor golgi proteins , and compared functional states of the golgi .\nthe speed of proteomics can produce petabytes of data far faster than we can analyze them .\nit thereby allows a wider range of comparative analyses than has so far been possible .\nthe roads opened by comparative proteomics will one day provide a complete map of all the cellular proteins in each organelle in each tissue at each stage of development . through comparison of this map with datasets generated from people with particular diseases , proteomics\nthe opening of the nuclear envelope by proteomics has already identified new inm proteins and produced a catalogue of yeast npc proteins .\nschematic of the nuclear envelope . the outer nuclear membrane ( onm ) and inner nuclear membrane ( inm )", "answer": "proteomic studies have the potential to comprehensively define the composition of organelles but are limited by the organellar cross - contamination that arises during subcellular fractionation . \n comparative proteomics of organellar subfractions can mitigate these problems , as demonstrated by a recent study involving the nuclear envelope .", "id": 454} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncryptosporidiosis is a parasitic disease that causes diarrhea lasting for about 1 - 2 weeks among the immunocompetent and becoming a more severe life - threatening illness among immunocompromised individuals .\nit constitutes 24% of human immunodeficiency virus ( hiv ) positive patients with diarrhea compared with 6.1% in the immunocompetent individuals .\nassociation of cryptosporidiosis with malignancies is not as robust as acquired immunodeficiency syndrome ( aids ) . here\n, we report a case of cryptosporidiosis causing severe persistent diarrhea in a patient with multiple myeloma .\nthe case we present here is the patient was a 64-year - old female who had been diagnosed to have multiple myeloma , stage iii b , type igg kappa 17 years ago in 1993 .\nshe was being treated with oral lenalidomide ( 25 mg for 21 days ) and dexamethasone ( 40 mg on days 1 , 8 and 15 ) of 28 days cycle for the current progression of myeloma .\nthe baseline serum m band prior to the start of this regimen was 3.4 g / dl .\nshe presented on day 17 of the 2 cycle with the complaints of profuse watery diarrhea , 10 - 12 times / day for the previous 15 days .\nthe diarrheal product was non - bloody , without any mucus and not foul smelling .\nthis was associated with nausea , mild crampy abdominal pain and a sense of fecal urgency without any fever .\nthere was anemia ( hemoglobin of 9.7 g / dl ) and leucopenia ( white blood cells count 2800/mm ) but the absolute neutrophil count ( 1700/mm ) and platelets were normal .\nthe liver and renal function tests were within normal limits but serum potassium was low ( 2.2 meq / l ) .\nthe routine blood culture was sterile and the polymerase chain reaction test in peripheral blood for cytomegalovirus deoxyribonucleic acid was negative .\nstool examination showed 2 - 3 polymorphonuclear leucocytes per high power field with mucus but no visible or occult blood .\ncolonoscopy was performed , which suggested colonic mucosal inflammation likely to be infective in origin [ figure 1 ] . at this point ,\na diagnosis of cryptosporidial infection was suspected and the stool was submitted for examination with the modified kinyoun acid - fast stain .\nthe patient was then started on oral nitazoxanide 500 mg 12 hourly for 10 days .\nthe diarrheal frequency decreased after 5 days and it resolved completely by the 10 day of this drug .\nthe patient was able to resume treatment with lenalidomide and dexamethasone later without any complications .\ncolonic mucosal inflammation on colonoscopy of the patient oocysts of cryptosporidium parvum in modified kinyoun acid - fast stain\ncryptosporidiosis is a protozoal intestinal infection caused by many species of the genus cryptosporidium that are either obligate human or human and bovine parasites .\nthe first association with human diarrheal disease was reported in 1976 , one case in an otherwise healthy child and one in an immunosuppressed adult . the infection is acquired by ingesting parasites in water or food contaminated by human or animal feces or by having contact with soil , a person , or an item that has been contaminated with the parasite . the diagnosis is established by demonstration of oocysts in the stool by the modified acid - fast kinyoun stain . since the initial reports\nfour clinical syndromes of cryptosporidial infection have been described in hiv positive patients : chronic diarrhea ( affecting 36% of patients ) , cholera - like disease ( 33% ) , transient diarrhea ( 15% ) and relapsing illness ( 15% ) .\nthe severity of illness is related to the cd4 count in these patients . in immunocompetent patients , usually children < 5 years of age\nthe clinical presentation in our patient with severe diarrhea of 2 weeks duration that resulted in dehydration and dyselectrolytemia was more consistent with an underlying immunodeficiency which is expected in a patient with long standing multiply treated myeloma .\nalthough uncommon , cryptosporidial diarrhea has been described in patients with malignancy . in one study ,\nthe incidence of cryptosporidiosis was 1.3% in the 560 cancer patients presenting with symptoms of diarrhea out of which 71% had hematolymphoid malignancy .\nin other studies it was found that the risk of severe disease is largely limited to children with acute leukemia and lymphoma .\ninterestingly , bone marrow transplantation does not seem to confer any additional risk over that of the underlying disease .\ncryptosporidial diarrhea should be included in the differential diagnosis of any patient with persistent severe diarrhea , especially in patients with hematological malignancies .\ndiagnosis can be established by stool examination and administration of nitazoxanide is effective in controlling the infection .", "answer": "cryptosporidiosis is a protozoal infection that leads to self - limited diarrheal disease in immunocompetent individuals and a more severe illness in immunocompromised patients especially those infected with the human immunodeficiency virus . \n although patients with hematolymphoid malignancies can develop this infection , it is an uncommon cause of diarrhea in these patients . \n the patient was a 64-year - old woman , a known case of multiple myeloma for 17 years , who had been treated with multiple lines of chemotherapy earlier . \n she was being treated with lenalidomide plus dexamethasone for active myeloma at the time of this episode . \n she presented with profuse watery diarrhea of 15 days duration that was proven to be due to cryptosporidium parvum on stool examination . the diarrheal illness resolved after treatment with nitazoxanide . \n although uncommon , cryptosporidial infection should be suspected in patients with hematological malignancies who have persistent diarrhea . \n stool examination with the modified acid - fast kenyoun stain establishes the diagnosis in the majority of cases . \n antiparasitic treatment is effective in controlling the infection .", "id": 455} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nincompetence in locating , cleaning and shaping or obturating the complete root canal system causes primary and post - treatment infections which often lead to endodontic treatment failures . however , the most significant reason for the root canal treatment failure is insufficient knowledge about the root canal morphology and its variations .\nthis is because such unexplored areas of root canal system remain unaffected by instruments and antimicrobial substances and form the seat for the persistent infection .\nthus , it is critical to assess the numerous morphological variations of the root canal system before initiating the endodontic procedure .\nhowever , certain internal and external morphological variations in the mandibular canine like single or bifid roots with two or three canals have been reported in the literature . till date , no case report on management of two rooted three canaled mandibular canine with a fractured instrument has been reported in the literature . in the documented case ,\ndental operating microscope is used to bypass the fractured instrument in the middle canal of a three canaled mandibular canine with the patients consent .\na 38-year - old healthy asian woman was referred to the endodontic clinic by a general dentist .\nthe patient presented to her dentist with a severe pain in left mandibular region ten days ago .\nthe dentist initiated the root canal treatment in left mandibular canine ( tooth # 22 ) . during the cleaning and shaping procedure , an iso # 10 k - file\nthe dentist could not bypass the fractured instrument and hence the case was opted for the referral . on clinical examination , tooth # 22 did not appear to have any coronal morphological variations and was identical to its right counterpart except it was mesially rotated .\nit was tender to percussion without any evidence of mobility , swelling or sinus tract .\ncareful pre - operative radiographic examination revealed a two rooted three canaled ( i.e. buccal , middle and lingual canals ) mandibular canine with a fractured instrument in the middle canal [ figure 1 ] .\nbuccal ( a ) , middle ( b ) and lingual ( c ) with a fractured instrument in the middle canal prior to the initiation of root canal treatment , patient was explained about the aberrant root canal morphology and presence of a separated instrument in the middle canal .\npatient was administered local anesthetic solution with adrenalin ( 2% lidocaine with 1 : 100000 epinephrine , lox 2% neon lab , india ) . under rubber dam isolation ( hygienic , coltne whaledent inc .\n, usa ) , access opening was re - defined with the help of ultrasonic tips ( pro ultra endo tips no . 2 and 3 , dentsply maillefer , new york , usa ) .\ncareful clinical explorations of access opening with a dg-16 endodontic explorer ( hu - friedy , chicago , il , usa ) revealed two root canal orifices in bucco - lingual direction and were present more towards the buccal side .\nmoreover , a bleeding point was noted lingually at the end of a developmental fusion line indicating the location of unexplored third root canal orifice .\ntroughing the developmental fusion line lingually with ultrasonic tips under a dental operating microscope ( carl zeiss surgical gmbh , oberkochen , germany ) revealed a third root canal orifice [ figure 2 ] .\nall three root canal orifices buccal ( a ) , middle ( b ) and lingual ( c ) present alongside the developmental fusion line ( d ) are located with the help of ultrasonic tips and dental operating microscope all the three root canal orifices were coronally pre - flared using a nickel - titanium ( niti ) protaper sx rotary file ( dentsply maillefer , ballaigues , switzerland ) with a brushing outstroke action to improve the straight - line access .\ndental operating microscope was used to visualize the fractured instrument present in the apical third of the middle canal . the maneuver to bypass the instrument was initiated in the presence of glyde ( dentsply maillefer , tulsa , ok ) by wedging an iso # 8 k - file ( dentsply maillefer , tulsa , ok ) between the fractured instrument and the canal walls with frequent radiographic checks .\nthe file was then advanced and withdrawn repeatedly in an attempt to widen the canal space and loosen the retained fragment from the root canal .\nso it was decided to prepare the entire root canal system , and incorporate the fragment into the obturation .\nthe space created between the fractured instrument and the canal walls was enlarged with the larger sized files sequentially till iso # 25 k - file .\nworking lengths for all three canals were determined with an apex locator ( root zx ; morita , tokyo , japan ) and were confirmed radiographically [ figure 3 ] .\nall three canals were prepared using protaper niti rotary instruments ( dentsply maillefer , ballaigues , switzerland ) according to manufacturer 's recommendations .\nprotaper s1/s2 rotary files were used with brushing outstroke action . finishing files f1 and f2\nirrigation was performed using triple distilled water , 2.5% sodium hypochlorite solution ( cmident , india ) and 15% edta ( largal ultra , septodont , saint maur des fosses , france ) .\n2% chlorhexidine digluconate ( r4 , septodont , saint maur des fosses , france ) . were used as the final irrigant .\nthe canals were dried with sterile paper points ( dentsply maillefer , tulsa , ok ) .\nthe access cavity was sealed temporarily with intermediate restorative material ( irm , caulk dentsply , milford , de ) .\nthe root canals were again irrigated with triple distilled water to remove the intracanal dressing of calcium hydroxide .\nobturation was done by a single cone technique with the use of gutta - percha cones and epoxy resin - based root canal sealer ( ah plus sealer , dentsply maillefer , tulsa , ok ) . in the middle canal ,\ntooth was restored using light cured composite resin ( z100 ; 3 m dental products ) .\nsubsequent follow - up x - ray was taken at 12 months [ figure 4b ] .\nworking length radiograph with fractured instrument bypassed in the middle canal ( a ) post - obturation radiograph with inclusion of a fractured instrument in the obturation .\nessential pre - requisites for a successful endodontic treatment are careful interpretation of pre - operative radiographs , a thorough knowledge and detailed exploration of internal root canal morphology and its divergence under the magnification and illumination .\nstraight radiograph provides information about the mesio - distal root canal orientation where as angled radiographs ( radiographs at two different horizontal angulations ) provide information about the facio - lingual canal position . any attempt to reduce\nthe required number of radiographs runs the risk of missing information of the complex canal morphology .\nfurthermore , a careful tracing of periodontal ligament space suggested the presence of two separate roots with three canals .\nthe access cavity was extended buco - lingually with the help of ultrasonic tips in order to conserve the tooth structure while searching for an extra and elusive canal orifice .\nthe internal and external morphological variations of the mandibular canine were clearly appreciable from the radiographic and clinical examination in the present case .\nhence , cone beam computed tomography ( cbct ) scan was not done to reduce any extra radiation dosages . even though the mandibular canine shows a single root and a single root canal with single apical foramen in about 92.2% of cases , clinicians should always search for any possible extra root or canal .\nroot canal morphological variations reported in the mandibular canine include two canals and one apical foramen in 4.9% of cases , two canals and two apical foramens in 1.2% of cases and two different roots each one with one canal in 1.7% of the cases . also two distinct case reports of mandibular canine with three canals in one root or two roots were reported in the past .\nhence , it is always prudent to consider all anatomical variations in the mandibular canine while performing a root canal treatment .\nany pre - determined assumption about the root canal morphology leads to failure to locate any morphological variation , if present .\nit hinders the effective cleaning and shaping and creates a nidus of infection that directly compromises the long term prognosis of the tooth . in the documented case , the fractured k - file in the middle canal prevented the negotiation and thorough biomechanical preparation of the canal .\nhowever , the chances of uneventful retrieval of the fractured instrument were not predictable considering the impossibility of visibility of instrument under dental operating microscope , strategic importance of tooth , the location of the instrument and the limited thickness of the root .\nsuccess in management of fractured instrument is defined as the complete removal or complete bypass of the fragment without creating a perforation .\nhence , decision was made to bypass the instrument under dental operating microscope to enhance the visualization of operating field and to conserve the maximum root structure . during the bypassing maneuver ,\nhigher magnification was used with frequent radiographic checks to avoid intra - operative complications like root perforation , ledge formation , pushing the instrument more apically etc .\nso , a clear understanding of pulp anatomy and its variations is essential if effective cleaning , shaping and obturation of the pulp space are to be achieved to assure the successful and predictable outcome of endodontic treatment .\nmandibular canine with variations in number of roots and root canals should be treated without any pre - operative assumptions regarding its typical single rooted and single canaled anatomy .\nthus the present case report highlights the endodontic management of an unusual case of mandibular canine with two roots and three canals .\nit also highlights the need for use of dental operating microscope and ultrasonics in locating the elusive canal orifices .\nso it is important to note the internal and external root canal morphological variations so that similar anatomy may be predicted and managed successfully . sometimes retrieval of a fractured instrument is impossible or undesirable . in these cases , bypassing the instrument under magnification is a valid alternative , which can lead to a favorable outcome as presented in the given case .", "answer": "it is important to assess the root canal morphology and its variations before initiating the endodontic procedure . \n this is because the inability to clean the complete root canal system forms the seat for the persistent infection which ultimately leads to endodontic treatment failure . \n this case reports the use of dental operating microscope for the successful endodontic management of a two rooted and three canaled mandibular canine with the fractured instrument in the middle canal of a 38-year - old healthy asian woman . \n this case report highlights the need to use the dental operating microscope and ultrasonics in locating the elusive canal orifices . \n it is important to note the internal and external root canal morphological variations before starting the endodontic treatment without any pre - operative assumptions about the usual anatomy of the toot .", "id": 456} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute mesenteric ischemia ( ami ) is an emergency situation that is caused by circulatory disturbances of mesenteric vessels and is frequently associated with atherosclerosis and cardiovascular disorders .\nami is a complex disease entity including acute mesenteric arterial embolism and thrombosis , mesenteric venous thrombosis , and non - occlusive mesenteric ischemia ( nomi ) .\nnomi results from low - velocity blood flow states or from mesenteric vasoconstrictions caused by some drugs .\nthe abdominal pain caused by intestinal ischemia is not proportional to the physical examination findings , especially in elderly persons .\nalthough computed tomography ( ct ) , magnetic resonance imaging and angiography are valuable diagnostic steps , definite diagnosis of intestinal ischemia frequently depends upon the clinical history because the representation would be subtle and obscure . the majority of patients with ischemic colitis can be treated medically , but approximately 20% of the patients clinically deteriorate to develop peritonitis and sepsis , necessitating surgical intervention with an associated 60% mortality rate [ 1 , 2 ] .\na laparotomy is helpful for rapid confirmation of the diagnosis and for optimal treatment , which often consists of revascularization and resection of the affected bowel .\nalcohol is well recognized as a systemic toxin that causes serious health problems , including psychosocial problems , myocardial infarction , stroke and atherosclerosis .\nwe reported a case of sub - acute ileal and colonic ischemia in an elderly patient , not having a history of cardiovascular disorders , after heavy alcohol intake , and we present a review of the literature .\nan 80-year - old male patient was admitted due to uncontrolled diarrhea and abdominal pain accompanied by fever . he became unconscious after drinking 1,800 ml of soju ( korean traditional drink\n, 25% distilled alcohol ) in one sitting and was then admitted to a local clinic . after conservative management\n, he woke up coherent , but he was referred to ewha womans university mokdong hospital because his diarrhea , fever and abdominal pain had not subsided after 10 days .\nhe had no history of chronic diseases such as diabetes , cardiovascular disease , hypertension , hepatitis or smoking .\nhe had had a drinking habit of half a bottle of soju ( 90 ml ) daily for forty years .\non admission , his blood pressure was 110/60 mmhg , his pulse rate was 84 beats / min , his respiratory rate was 24 breaths / min , his body temperature was 36 , and his mental status was clear . he had continuously suffered from diarrhea from the onset of the illness , 6 to 7 times daily , including night - time defecation . upon physical examination , there was mild generalized tenderness with abdominal distension on the whole abdomen and hyperactive bowel sound .\nlaboratory data included the following : leukocyte count , 14,100/l with no leftward shift ( neutrophil count , 61.8% ) ; hemoglobin level , 12.1 g / dl ; platelet count , 263,000/dl ; total protein , 4.8 g / dl ; albumin , 2.2 g / dl ; aspartate transaminase , 78 iu / l ; alanine transaminase , 103 iu / l ; blood urea nitrogen 8 mg / dl ; serum creatinine , 0.7 mg / dl ; amylase , 82 u / l ; creatine kinase , 48\nupright and supine roentgenograms of the abdomen showed the paralytic ileus with bowel distension ( fig .\nabdominal ct scan showed circumferential wall thickening of the bowel from the distal ileum to the ascending colon ( fig .\nfrequently the clinician finds no evidence of alcohol - induced hepatitis or pancreatitis that could be the cause of abdominal pain in patients suffering from alcohol abuse . upon the suspicion of ischemic colitis ,\nthe patient was treated with intravenous hydration , bowel rest , and broad - spectrum antibiotics .\nafter 5 days of treatment , he still had intermittent fever above 39 and severe cramping abdominal pain . on day 7\ndiffuse wall thickening of the terminal ileum to the transverse colon and a large amount of ascites in the pelvic cavity were noted in the ct scan ( fig .\nmucosal edema and multiple phlegmons were found on the ascending colon with colonoscopy ( fig .\n, symptoms such as diffuse abdominal distension , abdominal tenderness and rebound tenderness were aggravated ; hence , a laparotomy was performed .\nwhen the abdomen was opened , a small amount serous colored ascites was noted in the pelvic cavity .\nthe outer surface of the ileum ( from the ileocecal valve to the proximal 30 cm ) looked dark brown to blackish with severe edema and a weakening of the tissues of the bowel wall was observed .\nalso , the findings of the cecum and the ascending colon appeared to be similar to those of the affected ileum .\nthe gross appearances of the transverse and the descending colon and the sigmoid colon were almost normal .\npathologically , a diffuse acute infarction was present in the ileum and cecum , with acute vasoconstrictions of the mesenteric vessels .\na polyp of 0.4 cm was found on the ascending colon , 13 cm distal to the ileocecal valve , and was revealed to be a mucosal adenocarcinoma .\nthe postoperative course was uncomplicated , and the patient was discharge in good condition on the 15th postoperative day .\nnomi , the dominant non - thrombotic cause of acute mesenteric ischemia , results from low - flow states ( cardiogenic shock , sepsis , and hypovolemia ) , vasoconstriction , or occasionally drugs .\nnomi is defined as \" intestinal infarction without mesenteric vascular occlusion , \" and is the most lethal form of ami , with mortality rates of up to 70% [ 3 , 4 ] .\nthe condition commonly occurs in elderly patients , but a subset of young patients with mesenteric ischemia has been reported in the literature . in this young population , etiologies were reported as hypovolemic shock , vasculitis , and drug use .\nmedication and addictive drugs , such as digitalis , oral contraceptives , phenobarbital , ergotamine , furosemide and cocaine , have been implicated in the development of ischemic intestinal disease .\nfor a long time , alcohol has been known to be a precipitating factor of vasodilatation ; thus , after alcohol intake , the face becomes red , the blood pressure falls and the blood flow increases in the splanchnic vasculature . unlike such physiologic changes\n, pathological binge drinking is known to act as a vasocontricting situation and to be the cause of cardiovascular events . during the past ten years\n, alcohol consumption has come to be known as a risk factor for developing cerebral vascular diseases , such as stroke .\nseveral studies suggest that ethanol produces prolonged constrictions in cerebral blood vessels , and the vasoconstrictive actions of ethanol are involved in the hypoxic , ischemic and hemorrhagic actions on the brain [ 5 , 6 ] .\nalthough several studies have investigated alcohol 's effect on the vascular system , there are no reports that alcohol - caused mesenteric vasoconstriction directly causes intestinal ischemia .\nthe mechanism of alcohol - induced splanchnic vasoconstriction is unclear and is thought to be multifactorial .\nseveral mechanisms want for consideration to explain how alcohol causes bowel ischemia in spite of the difficulty in proving a direct causal relationship between the abuse of alcohol and intestinal ischemia . at first\n, alcohol may have a direct toxic effect on the gut mucosa and increase bacterial overgrowth in the small intestine [ 7 , 8 ] .\nthis persistent mucosal irritation is also likely to impair the susceptibility to abundant normal bacterial floras inside the bowel .\nanother indirect effect of alcohol on the mucosal microcirculation is an enhanced trans - capillary fluid filtration , increasing the permeability of the mucosa to macromolecules , such as endotoxin and/or other bacterial toxin that cause sepsis .\nin such a state , the intestinal infection has already started and may result in an irreversible clinical course .\nalcohol intake induces abnormalities in the plasma proteins that are required for blood clotting , leading to the formation of blood clots and the thrombotic occlusion of arterioles .\nalcohol may induce mesenteric vasoconstriction directly by suppressing the endothelium - dependent vasorelaxation , leading to reduced blood flow and ischemia . in our case ,\nthe patient had no history of any specific infection , had no predisposing factors for systemic vascular problems , and was healthy for his age .\nwe tried conservative treatment under the clinical diagnosis of acute gastroenteritis because there was no evidence of thrombus or constricted vessels in the first series of ct scans , but , in spite of bowel rest and conservative management , the symptoms continued for 15 days ( including the treatment period at another hospital ) without improvement\n. there were some differences between the operation findings and the ct findings . during surgery ,\nhowever , the distal ileum to the mid - transverse colon showed diffuse ischemic change , and there were much ascites .\npathological examination of the mesenteric vessels harvested revealed neither thrombosis or embolus within arteries or veins nor evidence of inflammatory bowel disease , such as systemic vasculitis and chronic granulomatous inflammation .\nextensive mucosal necrosis , which was associated with inflammation of the mucosa and vascular congestion , was consistent with nomi .\nit is doubtful that the clinical course of this patient would have been positive if prompt surgery had not been performed . recently , with increasing average life span , the elderly population has been increasing rapidly .\nmany studies on systemic vascular disorders in the elderly have been reported . in the case of emergency situations such as cerebrovascular disease or cardiovascular disease ,\nthe best procedure has been established relatively well . however , there are frequent occasions where even doctors can not diagnose an intestinal infarction when a patient presents with an acute abdomen .\nfortunately , with the improvement of high resolution ct , the accuracy of the diagnosis of an acute abdomen in the elderly is much improved .\nct may be helpful in determining the primary cause of bowel ischemia and in allowing direct evaluation of the bowel wall , the adjacent mesentery , and vascular structures .\nct is fundamental for early diagnosis and management when evaluating elderly patients with an acute abdomen , and we should have intestinal infarction in mind when evaluating patients with a history of binge drinking .\ndrug abuse , including excessive alcohol consumption in particular , has become a major health problem in korea .\nthis report established that , for successful treatment , mesenteric ischemia should be considered in the differential diagnosis of an acute abdomen in patients with a history of alcohol abuse .", "answer": "alcohol is well - recognized systemic toxin that causes numerous adverse effects , including psychosocial problems , fatal myocardial infarction , stroke and atherosclerosis . \n the intra - abdominal complications caused by acute alcohol consumption have not been defined . \n we report an 80-year - old man with sub - acute small bowel and colonic ischemia after heavy alcohol intake in one sitting . \n we performed a resection of gangrenous bowel segments . \n microscopically , there were diffuse infarction , with vasoconstriction of the mesenteric vessels in the ileum and colon without any thrombotic occlusion of the intestinal vessels . \n the clinicians should always be assured by confirmation of a history of recent substance abuse in patients with unexplained abdominal pain , and mesenteric ischemia should be considered in the differential diagnosis of acute or chronic abdominal pain in consumers of alcohol .", "id": 457} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmacular edema ( me ) is a complication of branch retinal vein occlusion ( brvo ) with serious adverse effects on vision.1,2 increased intravascular pressure and reduced blood flow in the macular capillaries lead to dysfunction of the endothelial blood\n retinal barrier and to increased vascular permeability , resulting in me.3 although grid laser photocoagulation was previously the only established treatment for me secondary to brvo , visual recovery was slow and limited.1 vascular endothelial growth factor ( vegf ) has been reported to play an important role in the pathogenesis of me secondary to brvo,46 and the introduction of intravitreal anti - vegf treatment has improved the visual prognosis of brvo;710 this treatment has consequently been adopted as the standard treatment . the effect of anti - vegf treatment on the absorption of me is rapid , but most eyes need to be treated repeatedly . in the horizon trial ,\nthe mean number of injections of ranibizumab was 2.02.4 in the second year after the initiation of the treatment for me associated with brvo.11 previously , some investigators reported the efficacy of pars plana vitrectomy combined with internal limiting membrane peeling for me associated with brvo.1220 it was reported that the reduction in me was not rapid after the surgery but the effect was maintained for years . for eyes with me refractory to repeated intravitreal injections of anti - vegf agents ,\nrecently , yunoki et al reported the efficacy of pars plana vitrectomy with internal limiting membrane peeling for recurrent me associated with brvo after intravitreal injections of bevacizumab.21 so far , however , limited information is available on this surgical intervention for recurrent or persistent me after anti - vegf treatment . in the study\ndescribed herein , we retrospectively investigated the anatomic and functional outcomes of eyes treated with pars plana vitrectomy combined with internal limiting membrane peeling for recurrent me due to brvo , in spite of anti - vegf treatment .\nfor this retrospective study , we reviewed the medical records of 24 eyes of 24 consecutive patients who underwent pars plana vitrectomy combined with internal limiting membrane peeling for recurrent me due to brvo after anti - vegf treatment at kagawa university hospital from october 2009 through december 2012 .\npatients were offered pars plana vitrectomy with internal limiting membrane peeling if they had visual loss caused by recurred me after intravitreal injections of anti - vegf agents .\nexclusion criteria were proliferative diabetic retinopathy , vitreous hemorrhage , central retinal vein occlusion , dense cataract , or a short follow - up period of < 6 months after the surgery .\neyes with previous focal scatter photocoagulation were included , but eyes with any previous treatments for me were excluded from the current study ( eg , intravitreal injections of any anti - vegf agent or triamcinolone acetonide , or grid laser photocoagulation ) .\nthis retrospective study was approved by the institutional review board of the faculty of medicine , kagawa university .\nthe study adhered to the tenets of the declaration of helsinki . we did not obtain written informed consent from each participant , because according to the guidelines of the institutional review board of the faculty of medicine , kagawa university , it is not necessarily mandatory to obtain informed consent from the patients for a retrospective study in which the researchers reviewed only the patients medical records .\nthe diagnoses of brvo and me were made by fundus examination and confirmed by fluorescein angiography and optical coherence tomography ( oct ) .\neach patient supplied a medical history and then underwent a complete ophthalmologic examination , including best - corrected visual acuity ( va ) measurement with a landolt chart , slit - lamp biomicroscopy , indirect fundus ophthalmoscopy , and oct examination . in each patient\n, digital fundus photographs and fluorescein angiography were obtained using a digital fundus camera ( trc-50lx ; topcon , tokyo , japan ) after pupil dilatation .\neyes with brvo were classified as ischemic when the area of nonperfusion was > 5 disk diameters in size.22 macular perfusion status was also determined as complete or incomplete , according to the previous report of finkelstein.23 repeated fluorescein angiography was performed if necessary . to evaluate the condition of me , oct examination was performed ( cirrus ; carl zeiss meditec ag , jena , germany ) at each visit .\ncentral retinal thickness ( crt ) was determined as the average retinal thickness in a 1 mm diameter circular region at the fovea . in the current study , patients who suffered visual disturbances due to me associated with brvo were offered intravitreal injection of bevacizumab ( avastin ; genentech , inc . , south san francisco , ca , usa ) .\nthe inclusion criterion was eyes with a crt > 300 m . in this study ,\npseudophakic eyes were included , but eyes that had undergone a prior vitrectomy were excluded .\noff - label use of bevacizumab was approved by the institutional ethics committee ; the study protocol adhered to the tenets of the declaration of helsinki , and written informed consent was obtained from each patient .\nintravitreal injection of ranibizumab ( lucentis ; novartis international ag , basel , switzerland ) was also used for the recurred me after its approval in japan .\nfor the treatment for recurrent me , all eyes in the current study underwent a standard 25-g three - port pars plana vitrectomy .\nafter core vitrectomy , posterior vitreous detachment was induced if the cortical vitreous was adherent to the retina .\nthe internal limiting membrane was peeled ~3.0 disk diameters around the fovea with the use of brilliant blue g. during the surgery , no laser photocoagulation was performed on the nonperfusion area of brvo .\nstatistical analysis was performed using ibm spss statistics version 21.0 ( ibm corporation , armonk , ny , usa ) .\n, va measured with a landolt chart was converted to the logarithm of the minimum angle of resolution ( logmar ) .\nrepeated measurement of analysis of variance was used to analyze crt and va after the initiation of the treatment .\nstudent s t - test was used for comparisons of the change in va during the treatment between eyes classified by the initial retinal features .\nin the current study , 24 eyes of 24 patients with brvo ( ten women and 14 men ) were included ( table 1 ) . at the initial visit ,\nno eyes had previously been treated with intravitreal injections of any anti - vegf agent or triamcinolone acetonide , or grid laser photocoagulation .\nafter the comprehensive ophthalmic examinations , each eye was treated with an intravitreal injection of bevacizumab . immediately after treatment , a reduction in me was achieved .\nva was also significantly improved at 1 month after the initial injection ( p=0.0050 ) .\nhowever , all eyes showed recurrence of me , and 14 eyes were received additional injection of anti - vegf agents ( bevacizumab or ranibizumab ) .\nmean number of injections of anti - vegf agent was 2.331.46 ( table 2 ) .\none eye was also treated with a subtenon injection of triamcinolone acetonide for recurrent me .\nthe duration of the initiation of anti - vegf treatment to undergoing pars plana vitrectomy was 232 months ( mean , 10.89.0 months ) . in spite of the treatment for me , all eyes showed recurrent me with subjective visual disturbance .\ncrt was significantly reduced at 1 month ( p=0.031 ) after the surgery , and the reduction increased with time ( p=0.007 at the final visit ) . with the reduction in crt\nmean follow - up after the surgery was 13.810.8 months . at the final visit , however , improvement in va was statistically significant compared with baseline va ( p=0.048 ) , although not significant compared with va before the surgery ( p=0.078 ) .\nno serious complications were seen during or after the surgery . in the current study , mean follow - up after the initial treatment was 24.510.8 months .\ntable 3 shows the comparisons of the change in va and crt during the treatment between eyes classified by the initial retinal features .\nthe presence of cystoid spaces , serous retinal detachment , or subretinal hemorrhage under the fovea had no significant association with the change in va .\nhowever , the presence of epiretinal membrane showed a significant association with the visual recovery .\nalthough eyes without epiretinal membrane showed visual improvement ( 0.100.32 ) with the treatment , eyes with epiretinal membrane showed greater visual improvement ( 0.380.12 , p=0.012 , figure 2 ) .\nsince the branch vein occlusion study group reported the efficacy of grid laser photocoagulation for chronic me associated with brvo,1 grid laser photocoagulation has been the only established treatment for me associated with brvo . however , the visual recovery is slow and limited because the average number of lines gained in treated eyes is limited to 1.33 .\nnow , anti - vegf treatment is generally accepted as the first choice for me associated with brvo.79,24 indeed , the effect of anti - vegf treatment is rapid and remarkable . in the bravo study , the mean improvement in va was 16.6 and 18.3 letters with 6 monthly injections of ranibizumab ( 0.3 mg and 0.5 mg , respectively).10 however , most eyes need to be treated repeatedly . in the horizon trial ,\nthe mean number of injections of ranibizumab was 2.02.4 in the second year after the initiation of the treatment for me associated with brvo.11 the retain study showed that long - term outcomes in brvo treated with ranibizumab were excellent but that approximately half of the cases still required occasional injections after 4 years.25 although the anti - vegf treatment for me is convenient and has a rapid effect , repeated injections may be a burden for patients . in the current study , an intravitreal injection of bevacizumab achieved rapid reduction in me . in spite of repeated treatment for me , however , all eyes showed recurrent me with subjective visual disturbance .\nall our patients treated with pars plana vitrectomy with internal limiting membrane peeling achieved reduction in me . to date , some investigators have reported the efficacy of this surgical intervention for me associated with brvo.1220 however , most reports show efficacy for treatment - naive me , and limited information is available on recurrent me .\nrecently , yunoki et al showed promising effects of pars plana vitrectomy with internal limiting membrane peeling for recurrent me due to brvo after intravitreal injections of bevacizumab.21 in their report , the improvement in va was achieved as early as 1 month after the surgery while our patients did not as long as 6 months .\nthis surgical intervention may be a treatment option for me refractory to the anti - vegf treatment .\nvitrectomy may have beneficial effects on retinal ischemia by allowing oxygenated fluid to circulate in the vitreous cavity.26 in addition , vitreomacular attachment is suggested to be involved in persistent me in eyes with brvo .\ntakahashi et al reported that the incidence of me was higher in eyes with no or partial posterior vitreous detachment.27 therefore , induction of posterior vitreous detachment may contribute primarily to the absorption of me associated with brvo .\ninternal limiting membrane peeling may contribute to the complete removal of traction in the macular area .\nprevious reports showed that fovea cystoid spaces , fovea serous retinal detachment , and subretinal hemorrhage are signs of poor visual prognosis in brvo.2831 in the current study , these features had no significant association with the change in va .\nfinkelstein reported incomplete macular perfusion as a sign of good va prognosis in ischemic me.23 in the current study , perfusion status in either the extramacular or the macular area showed no significant association with va improvement .\nhowever , the presence of epiretinal membrane showed a significant association with the visual recovery .\nphysicians sometimes see eyes with me due to brvo together with a fine epiretinal membrane . in case\nthe epiretinal membrane is the primary cause of visual disturbance , surgical intervention is indicated . because the treatment effect of anti - vegf agents is limited in vitrectomized eyes because of rapid clearance,32 physicians tend to choose anti - vegf agents as the initial treatment for me even if it is accompanied by a fine epiretinal membrane .\npreviously , marticorena et al reported that intravitreal bevacizumab may be associated with early development of epiretinal membrane in eyes with retinal vein occlusion.33 when such eyes show persistent me , surgical intervention may help .\nthis study has several limitations , mainly the small sample size ( especially eyes with epiretinal membrane ) and retrospective study design . in the current study ,\na recent report by yunoki et al showed no favorable va change in eyes with epiretinal membrane or vitreomacular traction after surgery . small sample size in the current study may account for the discrepancy.21 in addition , the noncomparative design of this study prevented determination of whether surgical intervention improved the visual prognosis . in the current study ,\nhowever , as shown in figure 1 , while the reduction in crt was already significant at 1 month , postoperative improvement in va was slow .\nin addition , mean va change at 1 month in eyes with combined cataract surgery ( 0.060.33 ) was not different , compared with eyes without ( 0.000.12 , p=0.525 ; data not shown ) .\nin the retrospective study reported herein , pars plana vitrectomy combined with internal limiting membrane peeling showed efficacy for recurrent me associated with brvo after anti - vegf treatment .\nthere is no doubt that anti - vegf treatment is the first choice for me associated with brvo . for recurrent me ,\nthis is a small case series ; therefore , a prospective study with larger sample populations is necessary to evaluate the efficacy of surgical interventions in such eyes .", "answer": "purposeto evaluate the anatomic and functional outcomes of pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema ( me ) due to branch retinal vein occlusion ( brvo ) after intravitreal injections of antivascular endothelial growth factor ( anti - vegf ) agents.methodstwenty-four eyes of 24 patients with treatment - naive me from brvo were treated with intravitreal injections of anti - vegf agents \n . recurred me was treated with pars plana vitrectomy combined with internal limiting membrane peeling.resultsafter the surgery , me was significantly reduced at 1 month ( p=0.031 ) and the reduction increased with time ( p=0.007 at the final visit ) . with the reduction in me , \n treated eyes showed a slow improvement in visual acuity ( va ) . at the final visit , \n improvement in va was statistically significant compared with baseline ( p=0.048 ) . \n the initial presence of cystoid spaces , serous retinal detachment , or subretinal hemorrhage under the fovea , as well as retinal perfusion status , showed no association with va improvement . \n however , the presence of epiretinal membrane showed a significant association with the visual recovery . \n although eyes without epiretinal membrane showed visual improvement ( 0.100.32 in logarithm of the minimum angle of resolution [ logmar ] ) , eyes with epiretinal membrane showed greater visual improvement ( 0.380.12 in logmar , p=0.012).conclusionfor recurrent me due to brvo after anti - vegf treatment , particularly when accompanied by epiretinal membrane , pars plana vitrectomy combined with internal limiting membrane peeling might be a possible treatment option .", "id": 458} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntrauma to the popliteal arteries resulting in pseudoaneurysm formation is rarely encountered outside the setting of wartime surgery [ 1 , 2 ] .\npopliteal pseudoaneurysms ( pps ) account for < 4% of all popliteal artery aneurysms , and hence experience of their management in individual centres is limited [ 35 ] .\nthe diagnosis of pp may also be delayed due to long - time interval between the initial trauma and symptom onset .\nwe present the case of a large pp causing acute limb ischaemia to a 37-year - old man .\nan otherwise healthy 37-year - old man presented with acute limb ischaemia of recent onset .\nhis past medical history was significant for smoking as well as a previous gunshot wound to the right lower limb 12 years previously that required fasciotomies .\ndiagnostic work - up included an arterial duplex scan of the right lower limb , which demonstrated a 5.5 cm 5.2 cm aneurysm of the right popliteal artery and the lack of flow in the right anterior tibial and peroneal arteries .\na ct angiogram was subsequently undertaken to establish the morphology of the aneurysm for preoperative planning , which confirmed the diagnosis but also demonstrated a large number of pellets in the soft tissues surrounding the right knee in keeping with the history of previous gunshot injury to the area .\npoor opacification of the right anterior tibial and peroneal arteries was also demonstrated , suggestive of thrombosis or embolization secondary to the popliteal aneurysm .\nangiography , via an antegrade right femoral approach , showed a false aneurysm of the popliteal artery at the knee joint level .\na 6 mm 25 mm viabahn ( gore ) covered stent was deployed to exclude the pseudoaneurysm , and a thrombolysis catheter was left in situ in the below - knee popliteal artery ( fig . 1 ) .\nthrombolysis was started using alteplase at a rate of 1 mg / h , with a concurrent infusion of heparin 400 iu / h via the arterial sheath , as per local protocol . \n figure 1:a digital subtraction angiogram of the right popliteal artery demonstrating the pseudoaneurysm , pre- ( a ) and post- ( b ) stenting .\na digital subtraction angiogram of the right popliteal artery demonstrating the pseudoaneurysm , pre- ( a ) and post- ( b ) stenting .\na repeat angiogram after 24 h of thrombolysis demonstrated improved patency while at 48 h excellent patency of the infragenicular vessels was seen ( fig . \n2 ) , and the patient was subsequently discharged on dual - antiplatelet and statin therapy . a follow - up arterial duplex performed at 6 weeks post discharge demonstrated excellent patency of the stent graft and infragenicular arteries . \n\nfigure 2:a digital subtraction angiogram at presentation ( a ) and after 48 h of continuous alteplase thrombolysis ( b ) demonstrating the improved patency of the infrapopliteal arteries .\na digital subtraction angiogram at presentation ( a ) and after 48 h of continuous alteplase thrombolysis ( b ) demonstrating the improved patency of the infrapopliteal arteries .\npps are a clinical entity that is rarely encountered in civilian medicine , and account for < 4% of all aneurysms of the popliteal artery [ 1 , 2 ] .\nits development is considered to be secondary to the formation of a thick fibrous pseudosac following arterial wall injury and haematoma organization .\nthis rather slow process may explain the usual delay in diagnosis which may range from days to years , with a median delay of 1.5 months .\nin our case , the delay in diagnosis was 12 years after the gunshot wound .\nthe usual presentation is that of a painful , pulsatile mass that may have given rise to complications that may threaten limb function or viability , including thrombotic and embolic events .\na wide range of options exist for the management of pps , including open surgical repair and endovascular treatment options .\nsurgical methods include the resection of the pseudoaneurysm with interposition grafting , ligation and bypass and primary arterial repair without grafting . finally ,\naneurysm resection and primary end - to - end anastomosis can be considered for small aneurysms .\nthe limiting factor , however , is the amount of perianeurysmal fibrosis and chronic inflammatory changes that are frequently encountered and hinder the safe performance of open surgical repair [ 1 , 6 ] . in this case , we elected to proceed with an endovascular repair .\nthe reasons were 2-fold : on one hand , the previous gunshot injury and the subsequent fasciotomies had led to significant deformity of the patients lower limb , while the amount of scarring would make access to the popliteal artery difficult , thus not favouring an open surgical repair .\non the other hand , the distal anterior tibial and peroneal artery thrombosis would require thrombolytic therapy and thus , the endovascular approach was considered more appropriate .\nthe false aneurysm was excluded with the covered stent prior to starting thrombolysis in order to eliminate the risk of distal embolization of thrombus from within the false aneurysm into the calf arteries during thrombolysis .\nendovascular repair has been shown to be a safe and efficient way of treating pps associated with lower morbidity and shorter hospital stay .\ncareful patient selection , however , is warranted , as increased risk of early occlusion has been reported , and hence may render this approach less desirable [ 7 , 8 ] .\ncovered stent placement was considered appropriate in this case in order to enable thrombolysis , which would not have been possible immediately after open surgical bypass .\nit is unclear whether stenting in this case will be the definitive treatment , as due to the young age of the patient and the anatomical location of the stenting , stenosis or occlusion of the stent is likely in the future . to this end\n, the patient has been put on a surveillance programme and will be followed up closely .\na short covered stent ( 25 mm ) was used to avoid compromising future graft anastomotic sites .\nthus , the endovascular treatment offered in this case was efficient in dealing with both the acute ischaemia secondary to thrombosis as well as the aneurysm itself in the short term .\non the other hand , the presence of a stent does not preclude open surgery in the future , preferably in an elective setting , and this is the approach the patient selected having being informed of his options .\nthis case report demonstrates the efficiency of stenting in the acute management popliteal artery pseudoaneurysms with encouraging early radiological and clinical outcomes .", "answer": "pseudoaneurysms of the popliteal artery are a rare clinical entity , accounting for < 4% of all popliteal aneurysms . \n accurate diagnosis and effective intervention is required to prevent potentially limb - threatening complications . \n we present the case of a 37-year - old man with acute limb ischaemia due to distal calf vessel thrombosis secondary to a popliteal pseudoaneurysm that was managed with covered stent placement and thrombolysis .", "id": 459} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\none of the most important health indicators in each country is maternal health ( 1 , 2 ) .\ntoday , the choice of cesarean section is one of the controversial issues in the health system of countries throughout the world ( 3 ) . because of its side effects and insensitivity , tendency for women to go ahead with vaginal delivery has decreased . due to the naturalness of vaginal delivery , the most favoured method of delivery is vaginal delivery ( 4 ) .\ndifferent factors such as the pregnant women s awareness regarding vaginal delivery , lack of awareness about the complications of cesarean section , fear of vaginal delivery , being encouraged by physician and the reduced role of midwives in training , have led to increased willingness of mothers for cesarean section ( 5 ) .\nmoreover , other factors such as maternal age , progress in surgical techniques , social and economic factors , supplemental insurance and health insurance coverage , lack of experienced midwives and lack of training in pregnancy period , have led to decreased willingness of vaginal delivery ( 6 ) . in recent years , according to the ministry of health data , the rate of cesarean section in iran has increased by 40 to 60% which is three times more than global standards ( 7 ) . although , according to who guidelines , the rate of cesarean section should be 515% ( 8) .\ncomplications of unnecessary cesarean section affect the health of the mother and children and increases economic burden .\nso , elective cesarean section is one of the most important challenges of health systems .\nit is essential for governments to perform effective changes in maternal health and also decrease the rate of elective cesarean section ( 9 ) .\nthe uncontrolled increase in the rate of unnecessary cesarean section is a major problem in the health system of iran ( 8) .\nhence , a program called the healthcare evolution plan has been implemented in iran since may , 4 , 2014 in order to fulfill the goals of the who .\n( specific goals include health , fairness in financial contribution and meeting the non - treatment expectations of the public ) .\none of the most important packages of this plan was to promote vaginal delivery ( 10 ) .\nit was expected that by the end of 2014 the rate of cesarean section would be reduced by as much as 10% ( 11 ) .\niran was the second highest country in the world to have caesarian section at the start of the project ( 8) . who guidelines emphasize that countries must improve maternal and infant health , by reducing the rate of cesarean section .\nthe present study was conducted to assess the impact of healthcare reform plans on the rate of vaginal delivery and cesarean section .\nfurthermore , the frequency and deviation of deliveries in public and private hospitals of provincial capitals were compared . in order to gain suitable strategies for policy makers in shiraz university of medical sciences ,\na comparison was made on the statistics related to 2013 ( one year before implementation of project ) and 2014 ( one year after implementation of project ) .\nthe main aim of this study was to examine the impact of the healthcare reform plan on the number of vaginal deliveries and cesarean sections , and its impact on the government adopted policies toward increasing vaginal delivery .\nthe rate of vaginal delivery and cesarean section in public and private hospitals were compared .\nfirst , descriptive statistics , related to the investigated period ( 20132014 ) were mentioned based on the number and percentage .\nthen the normality in the data was tested using kolmogorov - smirnov test . according to data distribution ,\nfinally , paired - samples t - tests and wilcoxon tests were used for assessing the hypotheses .\nthe accurate date registration , honesty in data analysis , presenting correct statistics according to the collected data , publishing the results in a simple language and presenting them to the authorities for correct decision and policy making , were taken into consideration and emphasized by the researcher .\nthe average number of vaginal delivery in 2013 was less than the average number of vaginal delivery in 2014 ( table 1 ) , it revealed that there is a significant difference between the number of vaginal delivery in 2013 and 2014 ( p 0.01 ) ( table 2 ) . by observing the average number of deliveries ,\nit was concluded that the health evolution plan was effective in increasing the number of vaginal delivery ( table 1 ) .\nhowever , the number of cesarean sections in 2014 had decreased in comparison to 2013 ( table 1 ) , was not significant ( p=0.772 ) ( table 2 ) . in this study ,\ndifferent indications for cesarean section were not considered . by observing the average number of deliveries , it is obvious that the healthcare reform plan has been influential in increasing the number of vaginal delivery .\nin addition , implementing healthcare reform has increased the number of vaginal delivery in public hospitals and decreased it in private hospitals .\nstatistical analysis indicated that there was a significant difference between implementing the healthcare reform plan and the number of vaginal deliveries in public hospitals ( p=0.019 ) ( table 2 ) .\nthe findings showed that there was not a significant difference between implementing the healthcare reform plan and the number of painless deliveries ( p=0.652 ) . despite the increasing number of painless deliveries in 2014 , ( due to the limited number of hospitals contributing in painless delivery )\n, no significant difference could be seen and it could be concluded that the healthcare reform plan was not influential in this aspect .\nthis study also revealed that there was not a significant difference between implanting the healthcare reform plan and the number of deliveries carried out by midwives ( p=0.428 ) . despite the increasing number of deliveries done by midwives in 2014 , due to the limited number of hospital using private midwives or lack of equipment for physiological delivery ,\npromotion of vaginal delivery and reducing the rate of cesarean section are the primary objectives of the healthcare reform plan in iran .\nvarious surveys have shown that the main reason of cesarean section is the repeated cesarean ( 12 ) .\nhence , proper planning is needed to reduce the number of cesarean sections in nulliparous women in order to prevent repeated cesarean sections in future .\nfear of vaginal delivery , mother s age and physician s recommendations are the most influential factors which encourage mothers to undergo cesarean section .\nso , holding consultation sessions before and during pregnancy could help mothers to choose the best method of delivery ( 13 ) .\nfurthermore , familiarity with delivery room , staffs , equipment , analgesia , presence of visitors and making the delivery room pleasant ( 14 ) are the factors reducing maternal anxiety , and aid the mother in choosing the best method of delivery . based on the instructions of mother - friendly hospitals ,\ntraining staff and physicians , limiting the use of elective cesarean section and cross section on uterus for possible vaginal delivery after cesarean section , were other factors which had influenced mothers choice and it had increased the number of vaginal delivery , and had decreased the number of cesarean section ( 15 ) . after the implementation of the health evolution plan , due to increase in the number of vaginal delivery , the government decreased the franchise of vaginal delivery to zero .\nit was expected that with the zero franchise of vaginal delivery , the number of patrons in public hospitals would increase and the number of vaginal deliveries would increase too .\nthe results of the present study showed that the percentage and number of vaginal delivery in public hospitals has been increased .\nhowever , implementation of healthcare reform not only decreased the number of vaginal delivery in private hospitals but also increased the number of cesarean section in those hospitals .\nthe main reason of decline in vaginal delivery in private hospitals was making vaginal delivery free in public hospitals and physicians limitations for cesarean section in public hospitals .\nfear was the most important reason - and also the main reason for nonmedical demand of mothers for elective cesarean section ( 11 ) .\nincrease in the number of painless delivery was another policy adopted by the ministry of health to promote vaginal delivery . despite the increased number of painless deliveries after the reform\nso , the number of samples for this type of delivery was little , and no significant difference was found between implementing healthcare reform and painless delivery .\nit can be predicted that the development of painless delivery facilities in other centers not only increase the number of vaginal delivery , but also improve equity in access of painless delivery .\nanother reason for mothers willingness for cesarean section is the fear of maternity units and lack of visitors . by the presence of trained visitors and providing the facilities with physiological delivery in hospitals ,\nusing midwives and making contracts with them in hospitals is another adopted policy to promote vaginal delivery ( 17 ) . despite the increased number of deliveries performed by midwives in 2014 , in comparison with 2013 , the limited number of hospitals having the facilities for vaginal delivery , and private midwives , led to the fact that there was no significant difference between the healthcare reform plan and delivery by midwife . with the launch of physiological delivery in all hospitals and benefiting from private midwives who have private offices ,\ntabrizi et al . also evaluated the health evolution plan . according to their nationwide study ,\nthe rate of cesarean section was 56.1% in 2013 , and in the first quarter of the project it had been decreased to 53.6% . besides this , the rate of cesarean section in public hospitals decreased from 47% to 42% after the reform however , the rate of cesarean section in private hospitals was 88% .\nit was revealed that the highest rate of decrease in cesarean section was related to public hospitals ( 5.3% ) .\nother hospitals such as social security hospitals ( 0.2% ) , and private hospitals ( 0.4% ) did not have any significant decrease .\nit indicated that the success of this project is in the public hospitals with more slope , thus more intervention is needed in private hospitals ( 18 ) . in 2013\nafshari et al . carried out another study to show the rate of cesarean section in the first eight months of implementing the healthcare reform plan in the hospitals affiliated to isfahan university of medical sciences .\nfinally , it can be concluded that implementation of the healthcare reform plan has been effective on the rate of vaginal delivery but it did not have such influence on private hospitals . according to the negative impact of the healthcare reform plan in the private hospitals ,\nit is suggested to increase tariffs of basic and supplementary insurance for delivery in private hospitals ( 20 ) .\nfurthermore , in a number of private hospitals there are no facilities for vaginal delivery . as a result of equipping these centers with delivery rooms and vaginal delivery facilities , developing physiologic delivery rooms , performing painless delivery , having contract with midwives , the number and percentage of vaginal delivery would be increased .\nit is suggested to determine the causes of cesarean section and separate the nulliparous cesarean section from repeated cesarean section in the study ( 21 ) .\nfirst , data for painless delivery and delivery by midwives in some centers were not available .\nsecond , we were not able to compare the reform with other studies because no similar reforms had been implemented in other countries .\none of the main aims of the health sector evolution plan in iran was to decrease cesarean section and increase vaginal delivery .\nour study showed that however the number of vaginal deliveries has increased during the reform , cesarean section has not been changed after the reform .\npolicy makers must find solutions to decrease cesarean section in the health care private sector . in this article ,\nit is suggested that other effects of the reform on iran health care delivery should be tested .", "answer": "introductionthe uncontrolled increase in the rate of cesarean section is one of the most controversial issues , and is a primary challenge among health policy makers . \n this study was conducted to examine the impact of the iranian health evolution plan on vaginal delivery rate and cesarean section.methodsthis cross - sectional study was carried out in 2014 . \n maternal health data for 2013 and 2014 were used in this study and changes in vaginal delivery and cesarean section were compared before and after the reform , using t - test and wilkinson test.resultsaccording to the findings of this study , 64.7% of deliveries in 2013 were performed using cesarean section while it was 58.6% in 2014 ( p= 0.772 ) , of which no significant changes were observed . \n in addition , the percentage of vaginal delivery in 2013 and 2014 were 35.3% and 41.4% respectively ( p= 0.00 ) , so a significant increase was found for vaginal delivery.conclusionhealthcare reform has led to an increase in the number of vaginal deliveries in hospitals affiliated to shiraz university of medical sciences ( sums ) . due to the limited number of hospitals adhering to the healthcare reform plan to increase vaginal delivery ( using private midwife and implementing painless delivery ) , the reform for decreasing the cesarean rate was not effective enough .", "id": 460} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfirst described by cushing in 1898 , chyle fistula can induce severe nutritional , metabolic and immune disturbances , delay wound healing , prolong hospital stay and , in the past , even resulted in death [ 1 , 2 ] . the incidence rate reported in the literature ranges from 0.5 to 2.5% [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] . in thyroid surgery , the rate of chyle fistula increases significantly ( p < 0.001 ) with the extent of the surgical procedure : 0.5% after less than total surgery with central compartment node dissection ( ccnd ) , 0.8% in patients with total thyroidectomy and ccnd , 5.1% after total thyroidectomy associated with ipsilateral neck dissection , and 6.2% in patients treated by total thyroidectomy with bilateral neck dissection . due to anatomic reasons ( left side termination of thoracic duct in 7592% ) ,\nthese injuries occur predominantly on the left side in patients undergoing lateral neck dissection [ 3 , 5 , 9 ] .\nreported a higher but not significant incidence of chyle leakage on the right side ( 8.9 vs. 7.5% ; p = 0.802 ) .\nmost chyle fistulas ( 2575% ) develop postoperatively , with a 86% rate of occurrence between the first and the third postoperative day .\na 27-year - old woman was referred to our department for the surgical treatment of a goiter with hyperthyroidism treated for 2 years with neomercazole 10 mg / day and levothyrox 50 g / day .\nultrasonography showed a suspicious 11-mm nodule in the left superior lobe and two ipsilateral 20-mm cervical nodes .\nfine needle cytology aspiration of cervical lymphadenopathy confirmed the involvement of a papillary thyroid cancer . in may 2010 ,\npathologic specimen examination showed a 12 15 mm papillary cancer in the left superior lobe without extrathyroid extension .\n, a high - output lymph fistula with milky appearance was observed following a drainage collection of 2,300 ml .\nwe decided to adopt a conservative medical management consisting of a diet of medium - chain triglycerides for 3 days .\npersistence of the fistula ( 1,400 ml / day ) on day 6 led to the introduction of a strict diet and parenteral nutrition , followed by a 50% reduction of the daily drainage ( 700 ml / day ) of the chyle fistula . on day 8 , after adjunction of a pharmacological treatment with subcutaneous octreotide ( 0.1 mg every 8 h ) , the fistulous debit decreased gradually until it disappeared completely after 6 days ( fig .\noral nutrition was initiated and the cervical closed suction drains removed . on postoperative day 16 , the patient was discharged home in good condition with correct wound healing .\none month later , the patient underwent a radioablation therapy ( 3.56 gbq ) after a radioiodine scanning revealed no persistent disease or distant metastases .\nafter a follow - up of 10 months , this young female had no signs of either local and/or distant recurrence or of postoperative functional and cosmetic sequelae .\npriority must be given to the prevention of lymph fistulas related to an injury of the main thoracic duct or one of its multiple branches ( 40% of cases ) [ 3 , 6 , 8 , 10 ] . a meticulous surgical technique combined with magnifying glasses has recently been advocated by lorenz et al . .\nintraoperative diagnosis of lymphatic leakage is better treated immediately by ligature ( 3 - 0 or 4 - 0 non - absorbable ) than suture procedures [ 6 , 9 ] . in most cases ,\npostoperative diagnosis is clinically obvious and no complementary investigations such as lymphoscintigraphy and/or ct scan are required [ 3 , 8 ] .\nchyle fistula usually starts after an oral diet , with an increase of drainage volume with milky appearance , swelling of supraclavicular fossa , erythema or induration of the skin [ 3 , 6 , 8 ] .\nmeasurement of triglyceride concentrations in postoperative fluid drainage may assist the early diagnosis of chyle fistula . a triglyceride level exceeding 100 mg / dl , a greater serum concentration or a lymphocyte count of 50% are thought to support the diagnosis [ 4 , 6 , 7 , 8 , 9 , 11 .\nalthough several therapeutic approaches , including nutritional , surgical and pharmacological procedures , have been proposed , there is currently no clear consensus on the optimal management of thoracic duct fistulas .\nthe decision between conservative and surgical treatment options still remains a subject of debate in literature reviews [ 5 , 6 , 7 , 8 , 11 ] .\nconservative medical management includes several lines of treatment and is imperatively associated with adequate drainage , applying pressure dressing , serial aspirations , bed rest and nutritional modifications [ 11 , 6 , 7 , 8 , 8 ] . except for initially large chyle leaks\n, conservative methods should be considered first since they allow a cure rate ranging from 58 to 100% .\nthe first step is an elemental diet supplemented with medium - chain triglycerides , directly absorbed into the portal circulation by passing the lymphatic system [ 4 , 6 , 7 , 8 , 9 ] .\nconversely , long - chain triglycerides entering the blood stream via the chyle should be avoided [ 4 , 7 , 8 ] . according to lorenz et al . , dietary restriction was less successful than total fasting . in case of failure and despite the increased costs , a total parenteral nutrition is recommended as a second - line approach in most institutions [ 4 , 6 , 7 , 8 ] .\nfurthermore , the optimal timing and the decision between conservative and surgical options remain unclear . for cokun\nothers [ 1 , 4 , 8 , 9 ] , a persistent drainage output of > 600 ml / day for 57 days despite medical conservative therapy or an extremely high output ( > 1.52 liters ) may require surgical re - intervention .\nmore recently , lorenz et al . have suggested a daily 300-ml output drainage threshold and an early decision on day 4 after initiating fasting protocol in favor of either continued medical treatment or surgery .\nthe aim of surgical therapy is to close the leak site with local application of fibrin glue , a pectoralis major muscle flap transfer or an absorbable mesh [ 6 , 7 , 8 , 9 ] .\nen bloc ligature of the thoracic duct by videothoracoscopy has also been proposed in patients who not respond to cervical re - intervention [ 2 , 3 , 5 , 9 , 11 ] . however , sclerotherapy devices with topical application of tetracycline or doxycycline have been abandoned because of local neurotoxicities ( phrenic or vagus nerve palsy ) [ 2 , 6 , 9 ] .\nsomatostatin and its long - acting analog octreotide were first described in 1990 by ulbarri et al . as an effective and successful adjunct to conservative therapy of iatrogenic thoracic duct injuries .\nthese preliminary data were confirmed 10 years later by markham et al . in a prospective study on dogs demonstrating a threefold decrease in thoracic duct fistula output after administration of octreotide .\nit reduces gastrointestinal chyle production by decreasing splanchnic blood flow and decreasing gastric , biliary , pancreatic and intestinal secretions [ 1 , 2 , 4 , 7 , 11 ] .\nadministered at a recommended dose of 3.512 g / kg / h for 314 days , octreotide therapy requires good monitoring of blood glucose levels every 6 h because of the inhibition induced by insulin , glucagon and motilin secretion .\nthe risk of cholecystitis secondary to cholestasis should also not be underestimated in patients eligible for prolonged treatment .\nin addition to recent data [ 1 , 4 , 6 , 7 , 8 , 11 , 15 ] , our observation demonstrated that octreotide is a promising alternative therapy useful for decreasing chyle fistula after thyroid cancer surgery and increasing the success of conservative management of this worrying complication .\nadvances in surgeons knowledge of the anatomic landmarks and variability of the cervical portion of the thoracic duct should minimize the incidence of injuries which lead to an often unrecognized but significant morbidity rate .", "answer": "the use of somatostatin analogs is a new conservative therapeutic approach for the treatment of chyle fistulas developing after thyroid cancer surgery . \n the combination therapy with a total parenteral nutrition should avoid the high morbidity of a re - intervention with an uncertain outcome . \n this promising trend is supported by the present case report of a chyle leak occurring after total thyroidectomy with central and lateral neck dissection for a papillary carcinoma , which was treated successfully without immediate or distant sequelae .", "id": 461} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe principal risk factors are tobacco smoking and alcohol consumption , and the association of both factors is highly synergistic .\ngenetic factors , dietary habits , human papillomavirus ( hpv ) infection , consumption of hot mate ( traditional south american infused drink ) , and poor oral health are also risk factors [ 35 ] . as lifestyles and human behaviour\nare directly affected by these factors , social inequalities are related to increases in risk .\nthe most recent oropharyngeal cancer incidence data of spain reveals that the country is situated amongst those that present elevated incidence in men , with rates of 3.6 cases per 100,000 inhabitants / year ( ci 95% = 3.43.8 ) , along with france , slovenia , switzerland , and germany . for women\n, spain is amongst the countries with lowest incidences , with a rate of 0.2 cases per 100,000 inhabitants / year ( ci 95% = 0.2 - 0.3 ) .\noropharyngeal cancer is rarely described separately from others head and neck tumours . the anatomical proximity between the oral cavity and the oropharynx , along with the fact that the risk factors are the same ,\nbesides , some publications analyse these locations in conjunction with other types of cancers that present different behavior and risk factors , such as nasopharynx and hypopharynx cancers , and denominate the entire group as oral cavity and pharynx cancer .\nother publications separate between oral cavity and oropharynx but include base of tongue cancers in the oral cavity classification , when the base of tongue should be analysed as a sublocation of the oropharynx .\nall these problems in the classification of oral cavity and oropharynx cancers hinder a more detailed analysis of the changes in epidemiological profiles , of the effect of treatment , and consequently , of the survival rates of both types of cancers .\nrecently , studies have proved that some risk factors are more related to specific locations , such as hpv infection and oropharynx locations , and tobacco and alcohol with oral cavity .\nthe objective of this study is to determine oropharyngeal cancer survival from the population - based cancer registry ( pbcr ) of zaragoza , spain .\ncancer survival analysis from population - based data constitutes a valuable tool for the evaluation of welfare services offered and allows for the orientation towards diagnose and treatment strategies .\nthe population studied was diagnosed with oropharyngeal cancer in the province of zaragoza , spain , between january 1 , 1978 and december 31 , 2002 .\ndata was actively collected , analysed , and monitored by the pbcr of zaragoza until december 31 , 2007 .\nthe following locations were included : base of tongue , lingual tonsils , soft palate , uvula , tonsils , and oropharynx ( icd codes : c01.9 , c02.4 , c05.1 , c05.2 , c09.0 , c09.1 , c09.8 , c09.9 , c10.0c10.4 , c10.8 y c10.9 ) .\nthe difficulty in establishing survival rates at a population level lies firstly in obtaining reliable data on cancer incidence for the population , and secondly , in carrying out the monitoring with accuracy and integrity .\nmonitoring of cases was carried out by the cancer registry itself through the mortality registry of the aragon government , which is administered by the statistical institute of aragon .\nall new cases registered as major salivary gland cancer were included in the analysis , except for the cases diagnosed through death certificates .\nthe pbcr data of zaragoza was the first spanish data to be published in cancer incidence in five continents , appearing in this publication since volume iii .\na set of quality indicators evaluates the data prior to publication in ci5 ; the registry data of zaragoza fulfils the established quality standards and presents excellent quality [ 13 , 14 ] .\ncalculation of the survival rate was carried out by the kaplan - meier method , and relative survival was calculated through the webpage of the catalan institute of oncology ( cio ) .\nthe relative survival rate is defined as the relationship between the observed survival and the expected survival in a group of healthy people of similar age and gender . in practice ,\nthe survival of people without cancer is difficult to predict , and for this reason the general mortality rate of the population is used .\nthe cio webpage uses the hakulinen method to calculate the relative survival of the database sent by the user and is based on the mortality tables of the mortality registries of the autonomous communities and provinces of spain [ 15 , 16 ] .\nwhen the number of risk patients was lower than 15 , these results were not considered in the analysis , as the final estimations were unstable .\nsurvival was studied by gender , age groups ( 4064 and over 65 years of age ) and location ( base of tongue , tonsils , soft palate , and oropharynx ) . in order to study the dynamics of survival\n, the data was stratified in three study periods ( 19781986 , 19871994 , and 19952002 ) , and the survival indicators were compared .\nthe effect of each prognostic factor ( sex , age group , location , and time period ) on the survival rates was evaluated by the log - rank test .\nthe log - rank test is a statistical hypothesis contrast test , used to compare two or more survival curves , and the null hypothesis is that the survival of the groups under comparison is the same .\nthe distribution of cases , number of deaths , and percentage of censored cases according to sex , age , and period are presented in table 1 .\nthe number of incidence cases included in the study was 380 , after exclusion of the cases registered through death certificates .\nit was observed that 87.6% of cases occurred in men ; the censored percentage was 26.6% ( 24.3% men and 42.6% women ) .\nthe observed survival after one year of diagnosis of oropharyngeal cancer was 61.3% ( ci 95% : 56.466.2 ) .\none - year relative survival was 61.9% ( ci 95% : 56.867.5 ) in men and 64.3% ( ci 95% : 51.970.8 ) in women ; five - year relative survival was 34.2% ( ci 95% : 29.240.1 ) in men and 53.3% ( ci 95% : 40.370.5 ) in women ( table 2 ) .\ncomparison of survival rates by sex revealed statistically significant differences ( p value = 0.017 ) with better survival in women .\nthere were no differences when comparing the three age groups ( p value = 0.61 ) , the locations ( p value = 0.25 ) , and the three studied time periods ( p value = 0.17 ) .\nthe continuous increase in the number of cancer survivors along with population ageing in spain , with a consequent increase in the number of cases , translate into new challenges that have to be overcome by the health care system .\nnowadays in spain , more than 50% of cancer patients are alive after five years of diagnosis and the trend is to increase this percentage . as a consequence of improvements in diagnose tests and treatments , an increase in cancer survivors is expected , and this situation creates new demands in welfare services , which must consider such complexity for patient monitoring .\nit is estimated that in 2015 in spain , 136,002 new cancer cases are diagnosed in men and 85,818 in women .\nactually , knowledge on the health situation of long - term survivors is still limited .\nit is known that the adoption of healthy lifestyles , selfcare attitude , and sociocultural and psychological aspects play an important role in the duration and life quality of patients [ 20 , 21 ] .\nthe eurocare studies are the most important survival data used for comparison purposes against this study .\neurocare is a multicentric project that gathers population - based cancer registries for european countries .\nsurvival data from this study shows that the highest survival rates are in western europe , independently from the period studied . for the 19901994 period ,\naverage survival for europe was 28.7% ( ci 95% = 26.031.5 ) in men and 43.5% in women\nthe highest survival rates occurred in sweden ( 46.6% , ci 95% = 40.753.4 in men and 56.2% , ci 95% = 47.566.4 in women ) , and the lowest rates were obtained in the czech republic , estonia , and slovakia .\nspanish data is within the european average , with a 29% five - year survival rate for men ( ci 95% = 24.035.0 ) and 44.1% ( ci\nspanish data originates from grenada , majorca , murcia , navarre , and tarragona . in zaragoza , the data encountered for the 19871994 period corroborates these findings , with a survival percentage of 30.4% ( ci\n, the average for all european countries reveals that 37.6% of men and 49.6% of women survived after five years of diagnosis .\nsweden and denmark presented the highest survival rates , with five - year survival rates of 45.3% ( ci\n95% = 26.042.0 ) , and the lowest survival rates were found in portugal and northern ireland .\nthe economic situation of countries and the amount of resources destined to welfare assistance are the main reasons for such a variation in survival rates and explain the lowest survival rates found in eastern europe .\nnevertheless , low survival rates in countries such as northern ireland or other regions of the united kingdom could also be associated with other aspects , such as the structure of the health care system , comorbidity , and risk factor patterns [ 24 , 25 ] . regarding gender ,\nthe results for zaragoza indicate that women present higher survival rates and most part of the studies found results in the same direction .\nthe reasons for these higher survival rates in women could be associated with a biological superiority of women in response to illness and treatment , or a higher awareness in women concerning their bodies , and consequently , a higher percentage of early - state diagnosis [ 24 , 26 ] . \nhigher survival rates in women were also found by another study , which investigated 89 population - based cancer registries in several european countries for the head and neck regions .\noropharyngeal cancer results demonstrate highest relative survival rates in women ( 47.67% ) than in men ( 37.67% ) , in younger ages and in northern europe . \nthe fact that along with an increase in age there is a significant decrease in survival has been published in all eurocare studies .\nthe reasons are comorbidity and the therapeutics used in elder patients , where many times surgical treatments are not indicated [ 22 , 23 ] . the results for the population of zaragoza did not show significant differences when comparing survival rates in the age groups of 4064 and over 65 years of age .\nthe low number of diagnosed cases in patients with 39 years of age or less prevented the survival rate analysis for this group .\nregarding location , it was observed that in zaragoza the highest survival rate was found for cancers located in the tonsils and the lowest , for those located in the tongue . a recent study carried out with data from the surveillance , epidemiology end results ( seer ) , a program of the united states national cancer institute , compared cancers located in the oropharynx with those in the oral cavity .\nthe results revealed a higher survival rate for cancers located in the oral portion of the tongue than for cancers located in the tonsils and base of tongue .\nthis division was adopted to differentiate those locations that supposedly present a higher risk for the development of cancers associated with hpv , such as oropharyngeal cancer , from those situated in the oral cavity .\nwhen comparing the three studied period , no statistically significant differences were found in the survival rates for oropharyngeal cancer in zaragoza .\nspanish results published in international studies do not demonstrate significant improvement in survival rates [ 22 , 23 ] .\nan investigation using canadian cancer registry data has studies changes in survival rates for oropharyngeal and head and neck cancers for patients diagnosed between 1992 and 2001 , totaling 10,860 cases in men and 4002 cases in women .\nthe results revealed significant improvements only in men , with an increase of 13.5% in the survival rates after five years .\nthe data presented herein suggest that zaragoza presents survival rates similar to other spanish registries already published .\nnevertheless , no statistically significant changes have been identified when dividing and comparing the total study period of 25 years in three study periods .\nthese results must be interpreted with caution because it is difficult to followup cases in such a long span study .\nalthough there are limitations , the authors consider that that survival studies using data from population - based cancer registries must be carried out and published , as they allow for the evaluation of the results obtained when treating the illness in the studies population .\ninvestigations such as the one presented herein can be the first step for the development of more effective treatment , prevention and control programs for cancer , improvement in the follow - up process of patients and future research .\nadvances in the treatment of cancer and the increase in the number of survivors call for a progressively wider monitoring of this part of population\nstudies on cancer survival need to increase follow - up time and broaden perspectives , with the objective of knowing the physical , psychological , and social aspects associated with this illness [ 18 , 30 ] .", "answer": "objective . \n this paper aims at studying oropharyngeal cancer survival from the population - based cancer registry of zaragoza , spain , for the 19782002 period \n . methods . \n the survival rates were calculated by the kaplan - meier method , and the automated calculation method of the catalan institute of oncology was utilized to obtain the relative survival . results . \n the oropharyngeal cancer survival rate was 61.3% in the first year and 33.9% in the fifth year . \n one - year relative survival was 62.2% ( ci 95% : 57.467.4 ) , and five - year relative survival was 36.6% ( ci 95% : 31.842.1 ) . \n comparison of survival rates by sex revealed statistically significant differences ( p value = 0.017 ) with better survival in women . \n there were no differences when comparing the three age groups and the three studied time periods 19781986 , 19871994 , and 19952002 . conclusions . \n the data suggests that there were no significant changes in oropharyngeal cancer survival in the province of zaragoza throughout the years .", "id": 462} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlevothyroxine ( l - t4 ) is used worldwide as replacement therapy for patients with hypothyroidism , and for the last few years it has been the third most commonly dispensed therapy in the united states .\nsynthetic l - t4 as a therapeutic agent was first used in the 1950s and was widely adopted as the primary agent for thyroid hormone replacement , replacing the natural desiccated thyroid extract that had been used over the previous 50-year period . although replacement therapy with levothyroxine has been prescribed for more than 60 years and is generally considered straightforward , cross - sectional surveys of patients on treatment with levothyroxine demonstrate that between 40% and 48% are either overtreated or undertreated [ 3 , 4 ] .\nfirstly , a number of factors may interfere with intestinal absorption of l - t4 , including food , dietary fibre , coffee , drugs , gastric or intestinal resection , and disease . as a result\n, current guidelines recommend that l - t4 is taken in a fasting state at least 30 minutes before breakfast [ 68 ] .\nsecondly , it is not always reliable to follow medical advice , especially for drug therapy ; this is especially relevant for l - t4 therapy as a significant number of patients have problems in postponing their breakfast by 3060 minutes to ensure that they take l - t4 in the fasting state . in the therapeutic scenario the recent introduction of nontablet l - t4 formulations , such as liquid and soft gel capsules , would seem to raise doubts as to this recommendation .\nthe results of a recent randomized , double - blind , placebo - controlled crossover trial showed that a liquid l - t4 formulation can be ingested during each patient 's normal breakfast , mixed with tea , coffee , milk , cappuccino , orange juice , and so forth , thus potentially improving therapeutic compliance .\nthis study , the titi study ( tirosint-versus - tiche study , ibsa italia ) , looked to extend these findings by investigating whether an l - t4 soft gel capsule formulation could also be safely and effectively administered to stable euthyroid patients during each patient 's normal breakfast without any malabsorption .\neligible patients were selected by a search in the database for those treated and followed up at the thyroid unit of the department of clinical and experimental sciences , university of brescia , italy . eligibility ( search ) criteria were as follows : ( a ) treatment of hypothyroidism with liquid l - t4 ( ibsa farmaceutici italia srl . , lodi , italy ) ingested during each patient 's normal breakfast ; ( b ) stable levothyroxine replacement over the last 6 months ; ( c ) complete personal medical history ; and ( d ) details of current drug therapy and any previous therapy . in order to avoid any possible confounders ( i.e. , the need to increase l - t4 therapy in patients affected by hashimoto 's thyroiditis during the study span ) we enrolled only patients who had previously undergone total thyroidectomy for proven benign goitre .\nall participants had to maintain the same breakfast habits and any ongoing therapy for the entire period of the study .\nall patients were assessed for thyroid - stimulating hormone ( tsh ) , free t4 ( ft4 ) , and free t3 ( ft3 ) levels and were switched from liquid l - t4 to the soft gel capsule formulation at the same dosage of l - t4 , ingested during each patient 's normal breakfast .\nserum concentrations of tsh , ft4 , and ft3 were once again established after six months .\nall patients gave their informed consent to participate in the study , conducted in accordance with the declaration of helsinki .\nserum concentrations of ft4 ( normal range 8.019.0 pg / ml , analytical sensitivity 1 pg / ml ) , ft3 ( normal range 2.44.7 , analytical sensitivity 0.35 pg / ml ) , and tsh ( normal range 0.44.5 miu / l , analytical sensitivity 0.004 miu / l ) were measured using a fully automated architect i2000 analyzer ( abbott diagnostics , abbott park , il , usa ) based on chemiluminescent magnetic immunoassay .\ntsh , ft4 , and ft3 levels distribution levels were nonnormally distributed and were not normalized by the usual procedures of data transformation ; in these cases results are presented as median with minimum and maximum values .\ncomparisons between continuous variables were performed by paired samples t - test or related samples by the wilcoxon signed rank test , as appropriate .\nof the 2371 assessed patients with hypothyroidism , 60 ( 51 females and 9 males , aged 47.7 11.2 years ) were eligible for the inclusion criteria and were enrolled for the study .\nall patients were euthyroid based on test results conducted 6 months before recruitment whilst receiving stable liquid l - t4 therapy ingested with breakfast ( mean dosage 106.25 24.28 g / day ) .\na detailed description of breakfast composition , particularly related to insoluble fibres and/or soya milk , was obtained in each subject ( table 1 ) .\nthe thyroid hormonal profiles during administration of liquid l - t4 six months before recruitment , at enrolment and after 6 months ' treatment with l - t4 soft gel capsules , are shown in table 2 .\nthere were no differences in tsh levels at the three different time points , but during treatment with the soft gel capsule formulation ft3 and ft4 levels were significantly lower than those found 6 months before recruitment and at enrolment with the liquid l - t4 formulation .\na subgroup analysis was conducted on the last 30 consecutive patients using data after three months of treatment with l - t4 soft gel capsules ( table 3 ) .\nthere were no significant differences in hormone levels between 6 months before recruitment , enrolment , and at 3 months .\nsignificant reductions in ft3 and ft4 levels were observed between 3 and 6 months ' treatment with l - t4 soft gel capsules whereas there was a slight increase in tsh value .\nthe main finding of this study is that both the liquid and soft gel capsule formulations of l - t4 can be taken with breakfast .\npriority should however be given to the liquid l - t4 formulation in those patients where even a small change in ft4 and ft3 levels is to be avoided .\ncurrent guidelines for the treatment of hypothyroidism recommend ingesting levothyroxine in the fasting state 6030 minutes before breakfast or at bedtime , at least three hours after the evening meal , for optimal and consistent absorption [ 68 ] .\nthis recommendation is based on study data demonstrating that concomitant ingestion of food [ 1215 ] , fibre , soya products , and coffee is associated with higher serum tsh values in hypothyroid subjects treated with l - t4 as compared with the fasting state . taking l - t4 with coffee , or with water followed by coffee within a few minutes , results in a poor tsh response in many patients .\nthe recent introduction of new nontablet formulations of l - t4 , such as soft gel capsules and a liquid , could resolve this problem .\nin one small study of hypothyroid patients , vita et al . observed that the absorption of a soft gel preparation of l - t4 ( tiche capsules , ibsa , switzerland ) was not impaired by taking it with coffee .\nthe same authors also reported that the problem of incomplete absorption of l - t4 caused by proton pump inhibitor - induced increases in gastric ph was not observed with the l - t4 soft gel formulation .\ndemonstrated that there is therapeutic equivalence in liquid l - t4 administration at breakfast or 10 min beforehand .\nwe have previously observed that taking l - t4 at 30 minutes before having breakfast was not associated with alterations in optimal tsh , ft4 , and ft3 concentrations in a group of patients taking their dose of a liquid l - t4 formulation ( tirosint , ibsa , italy ) with coffee .\nmore recently , we clearly demonstrated in a randomized , placebo - controlled double - blind crossover trial that the thyroid hormone profiles are almost identical after the administration of the same dose of oral liquid l - t4 either with breakfast or in the fasting state ( 30 minutes before breakfast ) .\n, no previous study has made comparisons between soft gel capsule and liquid formulations of l - t4 taken at breakfast time .\nthe clinical relevance of the significant reduction in ft4 and ft3 serum levels after switching from liquid to soft gel capsule l - t4 is not clear .\nnevertheless , further analysis of data on the last 30 patients would appear to indicate a progressive reduction in ft4 and ft3 levels after the switchover as time passed . at three months from switching over from liquid to soft gel capsule l - t4 , tsh ,\nft4 , and ft3 levels were superimposable on those found at recruitment , but reductions were seen over the next 3 months of therapy ( i.e. , by 6 months ) .\nthe tsh had again slightly increased but the change was not of statistical significance . based on these findings , it would be reasonable to assume that absorption of the soft gel capsule l - t4 formulation gradually diminishes as time passes when ingested with breakfast .\na longer follow - up during soft gel capsule treatment could yield further information on the trend of thyroid hormonal profile and the clinical significance of the hormonal changes demonstrated by this study .\nfor this reason , large longitudinal prospective studies are needed to clarify this important issue . in conclusion ,\nthe results of this study suggest that , in general , both the liquid and soft gel capsule formulations of l - t4 can be taken with breakfast .\npriority should however be given to the liquid l - t4 formulation in those patients where even small changes in ft4 and ft3 levels need to be avoided , such as those receiving suppressive therapy for thyroid cancer and/or cardiopathic patients receiving substitutive l - t4 therapy .", "answer": "background . \n recently , it has been shown that liquid l - t4 formulation can be ingested with breakfast . \n this study looked to extend these findings by investigating whether a soft gel capsule formulation of l - t4 could also be ingested at breakfast time . methods . \n 60 patients ( 1865 yrs ) , previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid l - t4 therapy ingested with breakfast , were enrolled . \n tsh , ft4 , and ft3 levels were assessed in all the patients who were switched from liquid l - t4 to a soft gel capsule formulation at the same dosage of l - t4 . \n after 6 months , tsh , ft4 , and ft3 levels were determined again . \n results . \n there were no differences in tsh levels , but ft3 and ft4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid l - t4 formulation ( tsh median ( min max ) : 1.9 ( 0.54.0 ) versus 2.2 ( 0.54.5 ) miu / l , ft3 : 2.5 ( 2.43.1 ) versus 2.7 ( 2.43.3 ) pg / ml , p < 0.05 , and ft4 : 9.9 ( 8.013 ) versus 10.6 ( 8.613.8 ) pg / ml , p < 0.0001 ) . conclusion . \n both liquid and soft gel formulations of l - t4 can be taken with breakfast \n . however , liquid l - t4 would be the preferred formulation for patients in whom even small changes in ft4 and ft3 levels are to be avoided .", "id": 463} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan 81-year - old diabetic male came to our hospital to seek medical attention for 2 weeks of productive cough , fever and chills , and a 10 kg weight loss .\nphysical examination revealed a fatigued - looking man with mild respiratory distress . except for bilateral crackles in both lungs , more on the right side ; the remainder of the physical examination was unremarkable , including the oral cavity .\ncomplete blood count revealed mild anemia , however , the patient did not have leukopenia / neutropenia .\na chest x - ray showed a right lung infiltrate ; thus , community - acquired pneumonia ( cap ) was suspected and the patient was admitted for treatment of cap .\nthe patient was started on intravenous gatifloxacin 400 mg daily . however , the patient 's symptoms continued to deteriorate while on gatifloxacin .\na chest computed tomography ( ct ) done on hospital day 3 , showed a right upper lobe cavitary lesion ( figure 1 ) . because of the cavitary lesion , pulmonary diseases more complicated than cap ( such as lung cancer or vasculitis involving the lung ) were suspected .\nthe patient underwent a bronchoscopy on hospital day 4 , which was reported as unremarkable .\nthe bronchial washing cytology examination did not reveal malignant cells , but it showed scattered elongated bacilli ( figure 2 ) . within 24 hours\nthe bronchial washing culture grew the same gram - negative bacillus , methicillin - sensitive staphylococcus aureus , viridans streptococcus and group b streptococcus .\nthe gram - negative bacillus was eventually identified as ls at the north dakota state laboratory ( figure 3 ) .\nblood cultures were drawn - once before starting antibiotics and three more times during treatment ; however , none of these cultures grew organisms . because of the clinical unresponsiveness to gatifloxacin , on hospital day 6 ,\nthe antibiotic was changed to intravenous vancomycin 1.5 g daily and piperacillin - tazobactam ( pip - tazo ) 3.375 g every 8 hours . \n\nfigure 1computed tomography - scan of the chest shows a cavitary lesion in the right upper lobe . \n \ncomputed tomography - scan of the chest shows a cavitary lesion in the right upper lobe . \n\nmagnification 400. \n papanicolaou stain of the bronchial washing reveals the elongated bacilli ( arrow ) .\nthe pneumonia was suspected to be caused by one of the above gram positive cocci and the ls was considered an oral contaminant ; therefore , after a 9-day course of vancomycin and pip - tazo , vancomycin was continued but pip - tazo was discontinued on hospital day 15 . on hospital day 19 , after reconsidering ls a remotely possible pathogen of the pneumonia , we added oral amoxicillin 500 mg / clavulanate 125 mg every 8 hours to the vancomycin regimen . while on vancomycin and amoxicillin - clavulanate , the patient began to have spiked fever , rigors and increased dyspnea . on hospital day 23 , a chest radiograph indicated worsening of the pneumonia .\npip - tazo was continued for 4 weeks , followed by 2 weeks of intravenous aqueous penicillin g 2 million units every 8 hours .\nthe patient continued to do well and has had no recurrence of pneumonia to date .\nls is an anaerobic gram - negative bacillus that resides in the oral cavity and usually does not cause disease .\nbacteremia , endocarditis , and hepatic abscess caused by leptotrichia buccalis have been reported in patients with neutropenia , hematologic malignancies and in bone marrow transplant recipients .\nmucosal disruptions such as oral mucositis , esophageal ulcers , or diverticulitis are possible risk factors for infected patients . by gram stain alone , ls can be confused with other oral commensals , such as the elongated gram negative fusobacteria sp , capnocytophaga sp or even with the gram positive lactobacillus sp as ls can sometimes be gram - variable .\nthe ls in this case report was identified by gram stain and phenotypic analysis , but not by gene sequencing because the north dakota state laboratory was not equipped to perform the test .\none case is cavitary pneumonia with bacteremia caused by l. buccalis in an immunocompromised host .\nthe other case is a severe pneumonia caused by ls in an apparently immunocompetent male patient .\nour patient has type 2 diabetes mellitus , but he is not immunocompromised from other underlying diseases or from immunosuppressive agents ; therefore , i believe this is the first case report of cavitary pneumonia caused by ls in an immunocompetent patient .\nalthough the patient had good dental hygiene without dental caries , gingivitis , or oral mucosa lesions ; the oral cavity could still be the portal of entry in this patient 's pneumonia .\npneumonia caused by ls could be underreported because ls is usually considered a normal oral flora and is difficult to identify .\ntherefore ; if ls grows from bronchoalveolar lavage or lung tissue , a clinician should consider it one of the etiologic agents causing pneumonia .\ndue to the rarity of human infection caused by ls , the duration of treatment for pneumonia caused by this bacterium is not clear . in our case , because the pneumonia recurred after we administered pip - tazo for only 9 days , we aggressively gave the patient 4 weeks of piptazo followed by 2 weeks of intravenous aqueous penicillin g. although there are no clinical and laboratory standards institute ( clsi ) breakpoints for ls , penicillins are considered the drugs of choice .\nthus , the patient continued to be clinically stable while on either pip - tazo or penicillin g. we postulate that the pneumonia recurred while on amoxicillin - clavulanate was likely due to the oral agent at a subtherapeutic level in the lung tissue .\ntherefore , we do not advocate treating pneumonia caused by ls with an oral -lactam antibiotic .", "answer": "leptotrichia species ( ls ) is an anaerobic gram negative bacillus in the bacteroidaceae family and part of the normal human oral flora . \n it is rarely pathogenic , but occasionally causes diseases in immunocompromised hosts . \n i am reporting a case of cavitary pneumonia caused by ls in an immunocompetent host .", "id": 464} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nng2 cells ( neuron - glia chondroitin sulphate proteoglycan 2 ) , also referred to as synantocytes , polydendrocytes , -astrocytes , oligodendrocyte precursor cells ( opc ) have been recognized as the fourth type of glial cells in the mammalian central nervous system , representing about 58% of the glial cell population .\nmorphologically , at light microscopy they resemble astrocytes , though their cell body is less rounded and cytoplasmic processes slender . at electron microscopy ,\nng2 cells show flattened nucleus with decondensed chromatin , well - represented cytoplasmic organelles and , where opposed to neurons , focal membrane densities .\nopposite to astrocytes , ng2 cells do not express gfap nor s100 protein , but express the ng2 chondroitin sulphate proteoglycan , a membrane protein with a large extracellular domain , whose function is still obscure . in the central nervous system , ng2 cells can be found in both gray and white matter and have been proposed as resident oligodendrocyte and astrocyte precursors . actually , their number increases in the vicinity of demyelization foci in some neuropathologies and after wound insult . on the other hand\n, ng2 cells do not express glutamate transporters , but have calcium - permeable ampa receptors , that cluster in apposition to nerve terminals , forming conventional synapses .\nthis feature suggests that these cells must have a more complex function than to be a simple reservoir of oligodendrocytes or astrocytes .\nthe cerebellum , which has a pivotal role in motor control , timing and learning , has been relatively neglected in studies concerning aging . in elderly people ,\nmovement and stability control are less efficient , with increasing fall risk and serious consequences and social costs . here\n, we describe that ng2 cells are not evenly distributed in the rat cerebellum and that their distribution and morphology undergo changes during aging .\nsprague dawley rats , aged 4 ( 3 animals ) and 28 months ( 3 animals ) , purchased from harlan nossan ( correzzana , italy ) and maintained in standard conditions ( 12 h light / dark cycle , 23c temperature , food and water ad libitum ) for few days were used .\nexperiments were performed in accordance with the italian and european community law for the use of experimental animals and were approved by a local bioethical committee .\nanimals were deeply anesthetized with chloral hydrate ( 0.35 g / g body weight ) and perfused transcardially with 4% paraformaldehyde in pbs .\ncerebella were excised , postfixed in the same fixative for 4 h and cryoprotected in 30% sucrose overnight .\ntwo out of every 10 sections were processed for immunocytochemistry for ng2 chondroitin sulphate proteoglycan as follows . briefly , after treatment with 3% h2o2 in 10% methanol in pbs and with 10% normal serum in pbs containing 0.1% nan3 , the sections were incubated overnight with 1:200 rabbit polyclonal antibody against ng2 chondroitin sulphate proteoglycan ( chemicon , billera , ma , usa ) .\nafterwards the sections were incubated for 90 min in anti - rabbit biotinylated igg , followed by streptavidin - hrp complex ( vectastain elite kit , vector , ca , usa ) .\n. some adjacent sections from 28-month - old rats were processed for calbindin immunocytochemistry ( with 1:5000 rabbit polyclonal antibody against calbindin , swant , ch ) to check for the integrity of the cytoarchitecture . for the reaction control\n, some sections were incubated with normal rabbit serum instead of the primary antibodies . to quantify the changes in the cerebellar area in which ng2 glia was densely scattered ,\nsections were photographed at low magnification and a morphometric analysis was performed using nih image j software .\nthe total section area and the area in which ng2 cells were densely represented ( relative area ) were measured by outlining the contours .\nsince the total area of cerebellar sections can vary with age and among animals of the same group , the ratio between the relative and total areas was calculated to standardize data .\nin the cerebellar vermis of 4-month - old rats , ng2 cells appear to be unevenly distributed . in lobules vi to viii according to larsell ng2 cells are uniformly and densely scattered in all cerebellar layers , including the white matter ( wm ) ; their long , slender cytoplasmic processes extend to form a spider web - like structure throughout all the cerebellar cortex ( figure 1a ) . on the contrary , in the more rostral and caudal lobules ( i vi and ix x ) ,\nonly sporadic cells may be observed in the wm and the granule cell layer ( igl ) , the majority of cells lying in the molecular layer ( ml ) .\nin addition , they appear less intensely stained than in the more central lobules ( figure 2a ) . in control reaction sections\nin fact , in mammals the central part of cerebellar vermis receives its main input from the cerebral cortex and is therefore called cerebrocerebellum . the anterior and posterior parts receive afferents primarily from the spinal cord and are therefore termed spinocerebellum . with regard to efferent connections ,\nthe cerebrocerebellum acts on the cerebral cortex and the spinocerebellum influences the spinal cord . in particular , the cerebrocerebellum receives information , via the corticopontine tract , about movements that are being planned and about commands that are sent out from the motor cortex . in response\n, it can modulate the activity of the motor cortex so that movements are performed accurately and smoothly\n. the high density of ng2 cells in the central lobules of the cerebellar vermis in the rat may therefore be due to a higher functional complexity of the cerebrocerebellum , which in turn requires a higher modulation from glial cells .\nthe functional significance of this rapid communication between neurons and ng2 cells is still obscure , but it has been suggested that through synapses ng2 cells can monitor neuronal activity and act consequently , maybe by releasing neurotrophic substances . \n\nfigure 1a , b ) representative sections of the cerebellar vermis of 4- and 28-month - old rats showing the distribution of ng2 cells .\nthe cerebellar area in which ng2 cells are uniformly and densely scattered ( dotted line ) is enlarged in aging animals ; c ) a section from a 28-month - old animal incubated with normal rabbit serum instead of the primary antibody .\nscale bar : 2 mm . \n a , b ) representative sections of the cerebellar vermis of 4- and 28-month - old rats showing the distribution of ng2 cells .\nthe cerebellar area in which ng2 cells are uniformly and densely scattered ( dotted line ) is enlarged in aging animals ; c ) a section from a 28-month - old animal incubated with normal rabbit serum instead of the primary antibody .\nfigure 2 in both 4- and 28-old rats , in the more rostral and caudal lobules of the cerebellum , ng2 cells are only sporadically present , mainly in the molecular layer .\ninset in b : in the molecular layer of both 4-and 28-month - old animals , immunostained cells show irregular soma and long , slender processes , typical of ng2 glia .\nscale bar a , b : 400 m ; inset 20 m . \n in both 4- and 28-old rats , in the more rostral and caudal lobules of the cerebellum , ng2 cells are only sporadically present , mainly in the molecular layer .\ninset in b : in the molecular layer of both 4-and 28-month - old animals , immunostained cells show irregular soma and long , slender processes , typical of ng2 glia .\nthe distribution of ng2 cells in the cerebellar vermis of 28-month - old rats is similar to that observed in 4-month - old animals .\nhowever , the area in which ng2 cells are more represented and uniformly scattered ( relative area ) appears to be enlarged , involving also the lobule v and part of the lobule ix ( figure 1b ) .\nmorphometric analysis revealed that the ratio between the relative and total areas of the sections is increased by 62% in aging animals ( 0.320.01 vs 0.520.02 , in 4- and 28-month - old rats , respectively ; p<0.0001 ) .\nthe expansion of the cerebellar area in which ng2 cells are densely represented in aged rats is an enigmatic finding .\nthe spinocerebellum is somatotopically organized as well as its afferent fibers , so that signals from different body parts are kept segregated .\nthe spinocerebellum is involved in the maintenance of the muscle tone and plays a role in the coordination of movements of walking .\ntaking into consideration that , if not exercised , muscle become hypotonic with aging , it is tempting to hypothesize that the increase in ng2 cells reflects a higher demand of neurotrophic factors or control from cerebellar neurons . obviously , this is a hypothesis that needs to be tested in animals subjected to daily exercise ( treadmill walking , for instance ) to maintain muscle tone , and that will have an unconfutable answer only when the function of ng2 cells will be fully elucidated . in aged rats , in lobules i iv and ix x , ng2 cells are no more present in the igl and wm and in the ml they appear paler ( figure 2b ) than in young - adult animal .\nhowever , punctate immunoreaction product is present in correspondence with the apical pole and stem dendrite of purkinje cells ( figure 3 ) .\nthe punctate reaction in lobules belonging to the spinocerebellum may represent profiles of hypertrophic ng2 cell processes that ensheath the soma and stem dendrite of purkinje cells .\nthis is the cell region where climbing fibers from neurons of the inferior olivary complex form the majority of synapses with purkinje cells .\nthe cerebellum/ inferior olivary complex system plays a major role as a comparator of sensory information and motor output . climbing fibers inform about errors in the execution of a movement , so that the cerebellum can adjust it .\nin this view , since climbing fibers establish synapses with ng2 cells , also ng2 cells could be informed and modulate purkinje cell activity accordingly . on the other hand , it can not be excluded that the punctate immunoreaction product represents extracellular product .\nin fact , the large ng2 proteoglycan ectodomain may be cleaved and released in the extracellular matrix .\nthis would also explain the pale staining of ng2 cells residing in the ml in 28-month - old animals . \n\nfigure 3a ) in the 4-month - old rat cerebellum , in the most rostral and caudal lobules , no immunoreaction product is present in the purkinje cell layer ; b , c ) representative photographs of portions of the most rostral and caudal cerebellar lobules in 28-month - old rats .\npunctate immunoreaction product is visible at the apical pole of purkinje cells ; d ) particular of the most caudal cerebellar lobules in a section immunostained for calbindin from 28-month - old rat .\nml , molecular layer ; pc , purkinje cell layer ; igl , granule cell layer .\nscale bar a , b , c : 20 m ; d : 50 m . \n \na ) in the 4-month - old rat cerebellum , in the most rostral and caudal lobules , no immunoreaction product is present in the purkinje cell layer ; b , c ) representative photographs of portions of the most rostral and caudal cerebellar lobules in 28-month - old rats .\npunctate immunoreaction product is visible at the apical pole of purkinje cells ; d ) particular of the most caudal cerebellar lobules in a section immunostained for calbindin from 28-month - old rat .\nml , molecular layer ; pc , purkinje cell layer ; igl , granule cell layer .\nscale bar a , b , c : 20 m ; d : 50 m .", "answer": "we describe by ng2 ( neuron - glia chondroitin sulphate proteoglycan 2 ) immunocytochemistry an uneven distribution of ng2 glial cells in the rat cerebellum , being them more represented in the central lobules of the cerebellar vermis , belonging to the cerebrocerebellum . \n the cerebellar distribution of ng2 cells changes in aging rats , in which the area where the cells appear to be densely scattered throughout all cerebellar layers involves also more rostral and caudal lobules . \n in addition , in aging rats , in the most rostral and caudal lobules belonging to the spinocerebellum , punctate reaction product is present at the apical pole of purkinje cells , i.e. in the area where the majority of synapses between olivary climbing fibers and purkinje cells occur . \n data suggest that the different distribution of ng2 cells is correlated to differences in physiology among cerebellar areas and reflects changes during aging .", "id": 465} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninstitutional review board approval ( irb0005239 ) was obtained as well as written consent from the mothers of both patients to use photographs of their children for publication .\na 3-month - old girl was referred to our tertiary eye clinic with a large capillary hemangioma covering her forehead , nose and the left side of her face [ fig . 1 ] .\nshe could only open the left eyelids to a vertical fissure height of 1 mm but was able to fix and follow with both eyes .\ncapillary hemangioma covering the left forehead , periocular area , nose , cheek , and upper lip as well as medial right upper lid at presentation oral prednisone ( 2 mg / kg ) and intralesional corticosteroid injections both failed to clear the visual axis while surgery and radiotherapy were considered inappropriate due to their unacceptable risk profile . the successful off - label use of ibi prompted us to use a test dose for her left upper lid and , 1 month later , the left palpebral fissure had noticeably increased in size .\nthe visible tumor was subsequently treated with monthly ibi using a dose of 0.5 mg / kg bleomycin diluted in a volume of normal saline equivalent to the estimated volume of the lesion .\ntreatment was discontinued after nine injections over 10 months since the final result was very satisfactory [ fig . 2 ] .\nten months later , after nine injections of intralesional bleomycin , the left visual axis is completely cleared and all treated areas show marked improvement a 10-week - old girl was referred to our clinic with a right periocular capillary hemangioma after earlier debulking surgery had not cleared the visual axis .\nexamination revealed a normal left eye as well as normal anterior and posterior segments on the right with complete mechanical ptosis due to the hemangioma [ fig . 3 ] . given the failure of surgical intervention , monthly ibi treatments of 0.5 mg / kg diluted in normal saline were commenced and no adverse effects related to the treatment were noted .\ntwo months after debulking surgery , a small notch , representing inadequate clearance of the visual axis , is visible in the right upper lid after five ibis , the right marginal reflex distance matched that on the left [ fig . 4 ] and the patient was orthophoric with no evidence of amblyopia .\nafter five intralesional bleomycin injections , the right visual axis has been cleared completely and regression of the remaining tumor has commenced no deterioration has been noted in either patient up to 12 months after the discontinuation of treatment .\na 3-month - old girl was referred to our tertiary eye clinic with a large capillary hemangioma covering her forehead , nose and the left side of her face [ fig . 1 ] .\nshe could only open the left eyelids to a vertical fissure height of 1 mm but was able to fix and follow with both eyes .\ncapillary hemangioma covering the left forehead , periocular area , nose , cheek , and upper lip as well as medial right upper lid at presentation oral prednisone ( 2 mg / kg ) and intralesional corticosteroid injections both failed to clear the visual axis while surgery and radiotherapy were considered inappropriate due to their unacceptable risk profile . the successful off - label use of ibi prompted us to use a test dose for her left upper lid and , 1 month later , the left palpebral fissure had noticeably increased in size .\nthe visible tumor was subsequently treated with monthly ibi using a dose of 0.5 mg / kg bleomycin diluted in a volume of normal saline equivalent to the estimated volume of the lesion .\ntreatment was discontinued after nine injections over 10 months since the final result was very satisfactory [ fig . 2 ] .\nten months later , after nine injections of intralesional bleomycin , the left visual axis is completely cleared and all treated areas show marked improvement\na 10-week - old girl was referred to our clinic with a right periocular capillary hemangioma after earlier debulking surgery had not cleared the visual axis .\nexamination revealed a normal left eye as well as normal anterior and posterior segments on the right with complete mechanical ptosis due to the hemangioma [ fig . 3 ] . given the failure of surgical intervention , monthly ibi treatments of 0.5 mg / kg diluted in normal saline were commenced and no adverse effects related to the treatment were noted .\ntwo months after debulking surgery , a small notch , representing inadequate clearance of the visual axis , is visible in the right upper lid after five ibis , the right marginal reflex distance matched that on the left [ fig .\nafter five intralesional bleomycin injections , the right visual axis has been cleared completely and regression of the remaining tumor has commenced no deterioration has been noted in either patient up to 12 months after the discontinuation of treatment .\nbleomycin was first isolated in 1966 by umezawa from a soil fungus , streptomyces verticillus .\nthe main mechanism of action of bleomycin is dna cleavage via oxidative damage caused by free radicals which form when its metal binding core is oxidized .\nbleomycin also induces apoptosis in rapidly growing cells and has a sclerosing effect on the vascular endothelium which makes it useful in the proliferating phase of vascular neoplasms .\nadditional mechanisms include blocking the cell cycle at g2 , degrading cellular rna and the induction of tumor necrosis factor .\nmany investigators have reported the successful use of ibi in treating hemangiomas and lymphangiomas in various anatomic locations .\none conservative estimate indicates that 56.2% of lesions treated with ibi will undergo 70100% regression although other reports indicate a significantly higher success rate .\nbasal cell carcinoma , kaposi sarcoma , keratoacanthoma and skin metastases of malignant melanoma have also responded well to ibis .\nbased on previous publications , we used the following technique and dosages : \n general anesthesia for all injections.dose : 0.5 mg / kg ( recommended range : 0.2 to 0.9 mg / kg per injection if aged under 1 year).volume : the dose in milligrams calculated above is then diluted in a volume of normal saline roughly equivalent to the volume of the lesion ; for example , if the lesion measures 1 2 2 cm = 4 cm , then the calculated dose is diluted in 4 ml normal saline.a multipuncture technique is used with a 23-gauge needle , entering through normal skin and advancing into the lesion.local pressure is applied for 10 min.oral analgesics are prescribed post-injection.review and retreatment are done every 4 weeks as needed . \n \ndose : 0.5 mg / kg ( recommended range : 0.2 to 0.9 mg / kg per injection if aged under 1 year ) . volume : the dose in milligrams calculated above is then diluted in a volume of normal saline roughly equivalent to the volume of the lesion ; for example , if the lesion measures 1 2 2 cm = 4 cm , then the calculated dose is diluted in 4 ml normal saline .\na multipuncture technique is used with a 23-gauge needle , entering through normal skin and advancing into the lesion .\npulmonary fibrosis is the most important dose - dependent complication of systemic bleomycin therapy but has not been reported after ibis . in one study ,\nno spill - over of bleomycin into the bloodstream could be demonstrated after ibis which could imply that the risk of developing pulmonary fibrosis after ibis is small .\nbleeding , ulceration , cellulitis , eschar formation , hypopigmentation , transient alopecia and flu - like symptoms may also occur .\nlymphangitis , flagellate hyperpigmentation , and raynaud 's phenomenon have been reported but are rare .\nthe side - effect profile of ibis therefore compares favorably with that of conventional treatment modalities . based on our experience\n, we would like to suggest that ibis also warrant consideration in the treatment of children with eyelid hemangiomas where conventional modalities have been unsuccessful or where treatment with beta - blockers may be contraindicated .\nthis could represent a significant step forward in the management of a condition that can prove very difficult to treat .", "answer": "periocular infantile capillary hemangiomas do not always respond well to conventional treatment modalities such as systemic or intralesional corticosteroids , radiotherapy or debulking surgery . \n the authors describe the use of intralesional bleomycin injections ( ibis ) to treat potentially amblyogenic lesions in two cases where other modalities have failed . in both cases \n monthly ibis successfully cleared the visual axis of the affected eye before the age of 1 year thus preventing permanent sensory deprivation amblyopia . \n a total of five and nine injections , respectively , were used and no significant side effects were noted . \n ibi appears to be a useful alternative in the treatment of periocular capillary hemangiomas refractory to more conventional modalities .", "id": 466} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsteven johnson syndrome ( sjs ) is characterized by sudden onset of erosion of mucous membranes ( predominantly oral mucosa , lips , and conjunctivae ) with widespread blistering of the skin involving up to 10% of the body surface area .\ntrimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections . in immunocompetent persons , the adverse reactions to\ntmp / smx occur in approximately 1 - 3% of persons . in contrast , in hiv - infected population\n, a much higher incidence of adverse reactions has been reported with frequencies ranging from 40 - 80% .\nwe report a hiv - infected man who developed sjs while receiving tmp / smx therapy .\na 33-year - old male presented with complaints of intermittent low grade fever for two months , cough with expectoration for one and half month , loss of weight , and appetite for one month .\nthe patient was afebrile with a pulse rate of 92/min , respiratory rate of 30/min and blood pressure of 120/70 mmhg .\ninvestigations revealed : hemoglobin 9.2 gm / dl , total leucocyte count 7500/cumm with an absolute lymphocyte count of 1500/cumm , platelet count of 2.1 lac / cumm and erythrocyte sedimentation rate of 76 mm at the end of 1 hr .\nhiv - elisa was positive . in view of the clinical presentation and investigations , a diagnosis of pneumocystis jirovecii pneumonia ( pcp )\nwas considered and the patient was started on tmp / smx doubles strength two tablets thrice daily .\nafter ten days of starting tmx / smx therapy , the patient developed high grade fever , redness and pricking sensation in eyes , and burning sensation in throat . within the next 48 hours he developed blepharitis , conjunctival congestion , erythema of the eyelids , and oral mucosal erosions [ figure 1 ] .\npainful , erythematous , maculopapular , and vesicular lesions appeared all over the body including genitals [ figure 2 ] .\nthere were multiple ulcerations in the buccal mucosa , floor of the mouth , and ventral surface of the tongue .\nthe patient was hemodynamically stable with a pulse rate of 102 per / min and a blood pressure of 110/80 mmhg .\nthe alanine aminotransferase and aspartate aminotransferase levels were 250u / l ( 10 - 40u / l ) and 155u / l ( 10 - 35u / l ) , respectively .\nthe patient was treated aggressively with intravenous dexamethasone 6 hourly , intravenous fluids , prophylactic antibiotics , anti - allergic drugs and local treatment of lesions .\nre - epithelialization of the previously sloughed areas occurred and the general condition of the patient remained satisfactory .\nhe was discharged after a month by which time the skin had healed with post - inflammatory hypopigmentation .\ndesensitization to tmp / smx was not attempted and the patient was discharged on dapsone prophylaxis for pcp .\nclinical photograph showing conjunctival congestion , erythema of the eyelids , and blepharitis clinical photograph showing cutaneous lesions all over the body with oral mucosal erosions\ntmp / smx is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in hiv - infected patients . in addition to its efficacy in preventing pcp , tmp /\nhowever , the administration of tmp / smx is hampered by the high incidence of hypersensitivity reactions in these patients .\nthe most common adverse reactions include nausea , vomiting , anorexia , dermatological reactions such as pruritis , urticaria and less commonly steven johnson syndrome ( sjs ) , neutropenia , exfoliative dermatitis , erythema multiforme and toxic epidermal necrolysis . a pubmed search using the keywords\n trimethoprim - sulfamethoxazole and steven johnson syndrome and human immunodeficiency virus revealed less than ten cases being reported in literature till date .\nthe increased incidence of adverse reactions to tmp / smx in hiv - infected patients is due to the hydroxylamine derivative of sulphamethaxazole , i.e. , sulphamethaxazole hydroxylamine .\nthe deficiency of glutathione enzyme in hiv - infected patients results in a decreased capacity to scavenge these hydroxylamine derivatives . in vitro\n, it has been found that as compared to cd8 cells , purified cd4 cells are more resistant to the sulphamethaxazole hydroxylamine . in hiv infection\n, the depletion of cd4 cells leaves a greater proportion of circulating t - cells as the more susceptible cd8 subset .\nin addition , the immune dysfunction observed in hiv - infected patients , i.e. , the polyclonal b - cell activation , polyclonal gammopathy , and decreased t - suppressor cell functions leads to an exaggerated humoral immune response to smx or its metabolites .\nother factors such as viral load and concurrent medications may also increase cell sensitivity to reactive metabolites .\nit is not clear whether the adverse reactions to tmp / smx merely indicate or also induce progression of hiv disease .\nveenstra et al . found that patients with adverse reactions to tmp / smx have a more rapid decline in cd4 cell counts and rapid progression to aids and death . in patients with non life - threatening adverse reactions ( e.g. , fever , rash ) , rapid or slow oral desensitization to tmp / smx\ncan be attempted . however , in patients with severe life threatening adverse reaction to tmp / smx , alternative drug like dapsone , pentamidine , or atovaquone should be given for pcp prophylaxis .\nthose who do not tolerate or have recurrent pcp infections despite alternative therapy could be subjected to a trial of desensitization to tmp - smx under close supervision .\nthis case illustrates a clinically important and life threatening adverse effect of tmp / smx in hiv - infected patients . due to the high incidence of such hypersensitivity reactions", "answer": "trimethoprim - sulfamethoxazole ( tmp / smx ) is a widely prescribed antimicrobial for the management of several uncomplicated infections . \n it is commonly used for the treatment and prophylaxis of pneumocystis jirovecii pneumonia ( pcp ) in the hiv - infected population . \n the adverse reaction to tmp / smx is more frequent and severe in hiv - infected patients as compared to the general population . here \n , we report a case of stevens - johnson syndrome ( sjs ) secondary to tmp / smx . \n the patient had a generalized cutaneous reaction with involvement of the eyes , oral cavity , and genitals . \n he had elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme . \n tmp / smx therapy was stopped and supportive treatment was started . \n his condition improved after eight days of stopping tmp / smx therapy .", "id": 467} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfollicular thyroid cancer ( ftc ) metastasizes most commonly to the lungs and non - cranial bones .\nskull and skin are uncommon sites and usually manifest well after the diagnosis of primary malignancy .\nmetastasis to skull and skin as the presenting feature of ftc is infrequently reported in the literature .\na 65-year - old caucasian woman with a history of thyroid nodule presented with the complaint of rapidly growing skull nodules which had been present for 3 years but were stable previously .\nshe denied any history of smoking or head and neck irradiation . on physical examination ,\nshe had two non - tender gray cystic lesions one on her left temporal region and the other on the right parietal region .\nmagnetic resonance imaging of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain .\nhistopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe .\nshe did not have any recurrence of the ftc or metastases during the follow - up period and will be receiving radioactive iodine treatment .\nbone and lung are the common sites of metastasis from ftc , but involvement of skull or skin is unusual , particularly as the presenting feature .\nmetastases from ftc should be in the differential of patients with new osteolytic hypervascular skull lesions or cutaneous lesions in head and neck area .\na 65-year - old caucasian woman with a history of thyroid nodule presented to dermatology clinic with the complaint of rapidly growing skull nodules .\nshe reported that the nodules had been present for 3 years but had been stable , so she had not sought medical attention .\nshe denied any fevers , chills , pain , or redness over the nodules , fatigue , weight loss , recent infections , or history of trauma .\nshe admitted to drinking alcohol on social occasions but denied any history of smoking or head and neck irradiation .\nher family history was positive for leukemia in her father and melanoma in her mother .\nshe indicated a remote history of thyroid nodule which she reported was benign on biopsy . on physical examination , she had two non - tender gray cystic lesions one on her left temporal region measuring about 5 cm in diameter and the other on the right parietal region measuring about 7 cm in diameter .\nlaboratory tests revealed a normal tsh of 0.52 iu / ml ( reference range 0.35.0 iu / ml ) and t4 of 0.68 ng / dl ( reference range 0.581.64 ng / dl ) .\na complete metabolic panel including serum creatinine , bun , and hepatic panel was normal .\nbiopsy was attempted under local anesthesia which revealed possible extension to the bone with vascular origin and hence the patient was referred to surgery for debulking . during surgery , total excision of the nodules could not be performed as there appeared to be skull erosion underneath .\nan immunohistochemical panel showed positive staining for ck7 , thyroglobulin , and hbme-1 while it was weakly positive for pankeratin , suggesting a thyroid origin of these lesions , that is , metastatic ftc ( fig .\ntwo large extra - axial enhancing masses with both intra- and extracranial components were seen ( figs . 2 , 3 ) . magnetic resonance imaging ( mri ) of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain ( fig .\n4 ) . positron emission tomography ( pet ) or ct of the skull demonstrated the two skull lesions to be lytic .\ntwo foci of hypermetabolic activity were also seen in the thyroid gland in the left lobe and thyroid isthmus .\nthyroid ultrasound showed numerous nodules in both lobes , the largest measuring up to 2.5 cm in greatest dimension .\nct head with and without contrast showing a large , round , relatively smoothly marginated enhancing extra - axial left frontal mass ( 4.4 cm in anteroposterior diameter and 4.1 cm in transverse diameter ) that has eroded and partially destroyed the calvarium and extends into the subcutaneous scalp .\nct head with and without contrast demonstrating a large , round , relatively smoothly marginated enhancing extra - axial mass ( measuring 6.8 cm in transverse diameter , 5.9 cm in ap diameter ) involving the right and left parietal region , straddling the posterior falx cerebri and superior sagittal sinus .\nmri brain revealing a large 7.13.8 cm fairly homogeneous enhancing relatively well - defined mass centered in the posterior calvarium with intracranial extension into the extra - axial space as well as extracranial extension .\nthere is a similar appearing 3.74.5 cm fairly homogeneous relatively well - defined enhancing mass centered in the left anterior lateral calvarium also extending into the extra - axial space as well as extracranially .\nhistopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe , pathological stage pt2nxm1 , a 1-cm focus of classic papillary thyroid cancer in the right lobe of thyroid , with a background of multinodular goiter ( fig .\nshe underwent intravascular embolization of the feeding blood vessels of her metastatic skull lesions from the external carotid system .\nthen she underwent resection of the tumor in multiple stages with resection of the posterior and left frontal tumor , and calvaria , followed by cranioplasty .\nalthough she had other unrelated postoperative complications , she did not have any recurrence of the ftc or metastases during the follow - up period , had a normal thyroglobulin of 4.9 ng / ml ( reference range 2.840.9 ng / ml ) , and will be receiving radioactive iodine treatment .\nit typically presents as a thyroid nodule , either noted by the patient or the physician on routine physical examination or incidentally on routine imaging ( 1 ) .\nvascular invasion is characteristic for follicular carcinoma accounting for more common distant metastasis ( 5 ) .\nthese metastases occur in 1015% of patients with ftc , with lung and bone being the commonest sites of involvement .\nbone metastases from ftc tend to be multiple and often involve sternum , ribs , and vertebrae ( 3 ) .\nskull metastases are uncommon with recent decline in incidence because of early detection and treatment of thyroid cancer ; among thyroid carcinomas , these metastases tend to occur more commonly in ftc and have a female preponderance ( 68 ) .\nthere were only 12 reported cases of skull metastases out of 473 patients of thyroid cancer in one study , accounting for 2.5% of cases ( 8) .\nlikewise cutaneous metastases from dtc are uncommon with less than 30 reported cases of cutaneous metastases in the english literature until 2010 ( 9 ) .\nthese cutaneous metastases are more common in head and neck region and can manifest in a variety of histological appearances ( 1012 ) .\nhowever , in most of these cases metastases occurred long after the diagnosis and institution of treatment for ftc and it is extremely unusual to encounter skull and cutaneous metastases as the presenting feature of ftc ( 3 ) .\nskull metastases from ftc most commonly present as a slow - growing soft , painless usually hemispheric and singular lump in the occipital region ( 6 , 7 , 12 ) .\nunusual presentations include headaches , hemiparesis , exophthalmos , cranial nerve dysfunction , and altered consciousness ( 13 ) .\nthese skull lesions are osteolytic on skull x - ray , and ct scans generally show homogeneous lesions with density slightly greater than the brain and a highly vascular appearance on angiographic assessment with blood supply most commonly from external carotid system ( 7 , 14 ) . in patients with scalp lesions , pet / ct can be used to determine the biopsy site ( 5 ) . in patients with established diagnosis of ftc with no documented metastases , evaluation of possible metastatic lesions can be done with ( 131)i single photon emission ct / ct [ ( 131)i - spect / ct ] ( 15 ) .\n( 99m)tc - mibi scan has been reported to be a highly sensitive technique for the detection of dtc metastases that have lost the capability to uptake ( 131)i ; the combined ( 99m)tc - mibi scintigraphy and serum thyroglobulin ( tg ) estimation appear to be an alternative method of radioiodine imaging in cases with dtc and elevated tg ( 16 ) .\nbone metastases uncommonly respond to radioactive iodine therapy and are associated with poor prognosis ( 7 ) .\nsurgical approach should be considered as one of the treatments of choice for bone metastasis , if possible , and curative resection of solitary bone metastasis is associated with improved survival ( 7 ) .\nbone defects often require extensive bone resection , bleeding is often profuse during surgical resection , and deaths have been reported from extreme hemorrhage ( 1 , 4 , 13 , 14 ) . because of the life - threatening nature of such hemorrhages , preoperative angiographic assessment of these lesions with prophylactic ligation or embolization of feeding vessels is recommended ( 14 ) . when surgical excision is not possible , internal radiation with i-131\nis recommended ; external radiation is generally reserved for cases where uptake of i-131 by metastatic foci is poor ( 8) .\nthyroid hormone should be administered after complete excision of thyroid gland to suppress endogenous tsh from promoting tumor growth ( 17 ) .\nfrequent follow - up examination is recommended and monitoring thyroglobulin measurement can be useful during follow - up ( 13 ) .\nftc is thought to have the most optimistic prognosis even with metastases to the lymph nodes and lung\n. however , when combined with distant , especially widespread , metastases , the quality of life is compromised and the overall survival rate significantly decreases ( 2 ) . in one case series , the mean time from the diagnosis of thyroid tumor until discovery of skull metastasis was 23.3 years ( 8) .\nprognosis in case of metastasis is generally poor and the 10-year survival with bone metastases from dtc is reported to be 27% ( 7 ) .\nhowever , mean survival time of 4.5 years was reported with skull metastases in one case series , suggesting even worse prognosis and warranting an aggressive and multidisciplinary approach in this subset of patients ( 5 ) .\na regular follow - up is crucial in these patients for early detection and management of any residual or recurrent metastatic ftc ( 6 ) .\nbone and lung are the common sites of metastasis from ftc but involvement of skull is unusual , especially as the presenting feature .\nmetastases from ftc should be included in the differential of patients with new oteolytic hypervascular skull lesions or cutaneous lesions in head and neck area ( 7 , 14 ) .\nthe authors have not received any funding or benefits from industry or elsewhere to conduct this study .", "answer": "backgroundfollicular thyroid cancer ( ftc ) metastasizes most commonly to the lungs and non - cranial bones . \n skull and skin are uncommon sites and usually manifest well after the diagnosis of primary malignancy . \n metastasis to skull and skin as the presenting feature of ftc is infrequently reported in the literature.case presentationa 65-year - old caucasian woman with a history of thyroid nodule presented with the complaint of rapidly growing skull nodules which had been present for 3 years but were stable previously . \n she denied any fevers , chills , history of trauma , or weight loss . \n she denied any history of smoking or head and neck irradiation . on physical examination , \n she had two non - tender gray cystic lesions one on her left temporal region and the other on the right parietal region . \n biopsy was consistent with metastatic ftc . \n magnetic resonance imaging of the brain demonstrated 7.13.8 cm and 3.74.5 cm fairly homogeneous , enhancing , relatively well - defined masses centered in the posterior and left anterior lateral calvarium with intracranial and extracranial extensions but without any vasogenic edema or mass effect on the brain . \n thyroid ultrasound showed numerous nodules in both lobes . \n the patient underwent a total thyroidectomy . \n histopathological studies of the thyroid gland revealed a well - differentiated ftc in the left lobe . \n then she underwent resection of the tumor in multiple stages . \n she did not have any recurrence of the ftc or metastases during the follow - up period and will be receiving radioactive iodine treatment.conclusionbone and lung are the common sites of metastasis from ftc , but involvement of skull or skin is unusual , particularly as the presenting feature . \n metastases from ftc should be in the differential of patients with new osteolytic hypervascular skull lesions or cutaneous lesions in head and neck area .", "id": 468} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nonly 30 - 60 per cent of patients respond properly to treatment with antidepressants , beta - blockers , statins and antipsychotic agents .\napproximately two days of prolonged hospital visits are caused by adverse drug reactions ( adrs ) , and , in the usa , about 100,000 deaths are estimated to be due to adrs every year .\nthese data emphasise an important problem that can be mostly explained by variable pharmacokinetics due , to a large extent , to differences in the activity of cytochrome p450 ( cyp ) enzymes involved in the metabolism of the drugs .\nvariable metabolism , in turn , can be caused by variation in the cyp genes , as is the focus of the current review .\nthere are 57 active cyp genes in the human genome , which are divided into 18 families . the first three families ( cyp1 - 3 ) are generally involved in the metabolism of exogenous substances such as drugs , whereas cyp families with higher numbers are usually involved in the metabolism of endogenous substances .\ncyp enzymes are responsible for 75 - 80 per cent of all phase i - dependent metabolism and for 65 - 70 per cent of the clearance of clinically used drugs .\nvariation in cyp genes results in phenotypes classically defined as ultrarapid , extensive , intermediate and poor metabolisers .\nan ultrarapid metaboliser ( um ) generally carries duplicated or multi - duplicated gene copies of the same allele , whereas intermediate ( i m ) and poor metabolisers ( pm ) characteristically carry one and two defective alleles ( eg gene inactivation or deletion ) , respectively .\nthe term extensive metaboliser ( em ) is normally used for subjects carrying two alleles giving normal activity of the cyp enzyme ( also called the * 1 or consensus allele ) .\nthe metaboliser phenotypes are mainly used for describing drug metabolism , but genetic variation in cyps with endogenous functions , such as in sterol , steroid , bile acid and fatty acid homeostasis , have also been well characterised , some of which give rise to disease states .\ncyp3a4 accounts for about 50 per cent of all cyp - dependent drug metabolism , although individuals ' capacity for cyp3a4-mediated drug metabolism is highly variable .\nno common genetic variants can account for this variation , despite the fact that 20 different alleles have been described .\nby contrast , cyp2c19 and cyp2d6 are highly polymorphic and together account for about 40 per cent of the metabolism of clinically used drugs .\nin addition , cyp1a2 , cyp2a6 and cyp2b6 are polymorphic enzymes that significantly contribute to xenobiotic metabolism .\nthe characterised genetic polymorphism of these enzymes provides a basis for the possibility to adjust drug dosage and choice of drug therapy according to genotype,[4 - 8 ] which includes avoidance of adrs , since polymorphic cyps are frequently the cause of these , either due to the formation of high levels of metabolites or because of decreased metabolism of the parent drug .\nimportant work in the cyp area focused on the identification and characterisation of polymorphic human cyp genes , which , in turn , created the need for a unified nomenclature system .\nthus , in 1999 , a nomenclature committee was formed with the aim of creating a platform for present and future allele nomenclature .\nthus , the human cytochrome p450 allele nomenclature ( cyp - allele ) website ( http://www.cypalleles.ki.se/ ) was launched with the purpose of managing allele designations , facilitating rapid online publication and providing a summary of alleles and their associated effects .\nthe nomenclature system chosen for the cyp - allele website was based on recognised nomenclature guidelines [ 9 - 13 ] .\ncurrently , the website covers the nomenclature for polymorphic alleles of 29 cyp enzymes and nadph cytochrome p450 oxidoreductase ( por ) ( see table 1 ) .\nthe cyp2b6 , cyp2c9 , cyp2c19 and cyp2d6 genes are particularly polymorphic , all with a high number of functionally different alleles .\neach of the genes at the cyp - allele website has its own webpage that lists the various alleles with their nucleotide changes , molecular and functional consequences in vitro as well as in vivo , and also publications identifying or characterising the alleles .\nin addition , links to the national center for biotechnology information ( ncbi ) single nucleotide polymorphism database ( dbsnp ) and papers with allele frequencies are presented .\nthe number of visits is relatively constant over time , about 36,000 per year , and the website is highly cited in publications in the field of pharmacogenomics .\npolymorphic genes covered on the cyp - allele website examples of some important variant alleles are given , as well as representative substrates the designation of an allele ( such as cyp2b6 * 4 ) ideally requires determination of all sequence variations in the gene , although sequencing the intronic regions is generally not necessary . on the website ,\na gene is considered as the sequence from 5 kilobases upstream from the transcription start site to 500 base pairs downstream of the last exon .\nif a regulatory element has been characterised at a more distant part of the gene , however , it too is considered to belong to the gene .\nall known sequence variations within an allele are described on the cyp - allele website , although new allele numbers are currently only designated for alleles that contain at least one functional variation causing consequences such as amino acid substitutions , translation terminations , splice defects , differential transcription rates etc .\nnevertheless , the allele is required to be well characterised regarding linkage or lack of linkage of the consequential snp with other nucleotide variations , including those in exons , intron - exon junctions and flanking regions .\ninferring haplotypes by program analyses is generally avoided , although such alleles have occasionally been included on the cyp - allele website . when the characterised sequence variant is found in different constellations with non - causative ( eg silent ) ones ,\nthe different combinations are defined as sub - alleles and receive letters in addition to the number ( eg cyp2b6 * 4a , cyp2b6 * 4b ) .\nwhen several effective polymorphisms are present on the same allele , however , the allelic number given is based on the polymorphism that causes the most severe consequence , such as a splice defect ( eg cyp2c19 * 2a ) , so alleles that additionally contain sequence variants with less severe effects will share the same allele number , together with an additional letter ( eg cyp2c19 * 2b ) .\ncombinations of variants that are also present alone and that are considered similarly effective ( eg different amino acid substitutions ) are given unique allele numbers ( eg cyp2b6 * 6 ) .\nnotably , the earliest described alleles on the website do not follow the nomenclature system , but the allelic designations have remained , for practical reasons . when new alleles are identified , relevant information is sent to the webmaster .\ninclusion criteria ( http://www.cypalleles.ki.se/criteria.htm ) involve complete characterisation of the gene sequence , covering exons and exon - intron junctions at the minimum , investigation of linkage with other sequence variants and potential in vitro or in vivo findings .\nit is advised that the authors of a manuscript that describes a novel allele contact the webmaster before submission , in order to review the data and assign a new allele name to be used in the manuscript .\nusage of star allele designations that have not been approved by the nomenclature committee is strongly discouraged , because of the apparent risk of confusion and of using the same allele name for different variants .\nall information sent to the webmaster is kept strictly confidential until publication of the manuscript or until the authors request it to be released .\nthus , there are likely to be allele names designated by the cyp - allele website that have not yet been published , further emphasising the importance of refraining from using unauthorised allele names .\nthe webmaster ( and in rare cases also the editorial and/or advisory board ) reviews the submission to evaluate whether there are enough data to support a new allele designation . only peer - reviewed data are thus published on the cyp - allele website .\npapers describing additional characterisation of a known allele -- with respect to , for example , in vitro or in vivo activity -- are also peer reviewed and can be linked to the respective allele on the webpage .\nsuggestions of papers that should be included with respect to further characterisation of alleles are appreciated .\nimportant work in the cyp area focused on the identification and characterisation of polymorphic human cyp genes , which , in turn , created the need for a unified nomenclature system .\nthus , in 1999 , a nomenclature committee was formed with the aim of creating a platform for present and future allele nomenclature .\nthus , the human cytochrome p450 allele nomenclature ( cyp - allele ) website ( http://www.cypalleles.ki.se/ ) was launched with the purpose of managing allele designations , facilitating rapid online publication and providing a summary of alleles and their associated effects .\nthe nomenclature system chosen for the cyp - allele website was based on recognised nomenclature guidelines [ 9 - 13 ] .\ncurrently , the website covers the nomenclature for polymorphic alleles of 29 cyp enzymes and nadph cytochrome p450 oxidoreductase ( por ) ( see table 1 ) .\nthe cyp2b6 , cyp2c9 , cyp2c19 and cyp2d6 genes are particularly polymorphic , all with a high number of functionally different alleles .\neach of the genes at the cyp - allele website has its own webpage that lists the various alleles with their nucleotide changes , molecular and functional consequences in vitro as well as in vivo , and also publications identifying or characterising the alleles .\nin addition , links to the national center for biotechnology information ( ncbi ) single nucleotide polymorphism database ( dbsnp ) and papers with allele frequencies are presented .\nthe number of visits is relatively constant over time , about 36,000 per year , and the website is highly cited in publications in the field of pharmacogenomics .\npolymorphic genes covered on the cyp - allele website examples of some important variant alleles are given , as well as representative substrates\nthe designation of an allele ( such as cyp2b6 * 4 ) ideally requires determination of all sequence variations in the gene , although sequencing the intronic regions is generally not necessary . on the website ,\na gene is considered as the sequence from 5 kilobases upstream from the transcription start site to 500 base pairs downstream of the last exon .\nif a regulatory element has been characterised at a more distant part of the gene , however , it too is considered to belong to the gene .\nall known sequence variations within an allele are described on the cyp - allele website , although new allele numbers are currently only designated for alleles that contain at least one functional variation causing consequences such as amino acid substitutions , translation terminations , splice defects , differential transcription rates etc .\nnevertheless , the allele is required to be well characterised regarding linkage or lack of linkage of the consequential snp with other nucleotide variations , including those in exons , intron - exon junctions and flanking regions . inferring haplotypes by program analyses\nis generally avoided , although such alleles have occasionally been included on the cyp - allele website . when the characterised sequence variant is found in different constellations with non - causative ( eg silent ) ones ,\nthe different combinations are defined as sub - alleles and receive letters in addition to the number ( eg cyp2b6 * 4a , cyp2b6 * 4b ) .\nwhen several effective polymorphisms are present on the same allele , however , the allelic number given is based on the polymorphism that causes the most severe consequence , such as a splice defect ( eg cyp2c19 * 2a ) , so alleles that additionally contain sequence variants with less severe effects will share the same allele number , together with an additional letter ( eg cyp2c19 * 2b ) .\ncombinations of variants that are also present alone and that are considered similarly effective ( eg different amino acid substitutions ) are given unique allele numbers ( eg cyp2b6 * 6 ) .\nnotably , the earliest described alleles on the website do not follow the nomenclature system , but the allelic designations have remained , for practical reasons .\ninclusion criteria ( http://www.cypalleles.ki.se/criteria.htm ) involve complete characterisation of the gene sequence , covering exons and exon - intron junctions at the minimum , investigation of linkage with other sequence variants and potential in vitro or in vivo findings .\nit is advised that the authors of a manuscript that describes a novel allele contact the webmaster before submission , in order to review the data and assign a new allele name to be used in the manuscript .\nusage of star allele designations that have not been approved by the nomenclature committee is strongly discouraged , because of the apparent risk of confusion and of using the same allele name for different variants .\nall information sent to the webmaster is kept strictly confidential until publication of the manuscript or until the authors request it to be released .\nthus , there are likely to be allele names designated by the cyp - allele website that have not yet been published , further emphasising the importance of refraining from using unauthorised allele names .\nthe webmaster ( and in rare cases also the editorial and/or advisory board ) reviews the submission to evaluate whether there are enough data to support a new allele designation .\npapers describing additional characterisation of a known allele -- with respect to , for example , in vitro or in vivo activity -- are also peer reviewed and can be linked to the respective allele on the webpage .\nsuggestions of papers that should be included with respect to further characterisation of alleles are appreciated .\nthe cyp - allele website is widely used and well acknowledged within the scientific community .\nit serves the purpose of a unified and easily accessible nomenclature system for cyp enzymes , as well as for the cyp electron donor por .\nthe purpose of the cyp - allele website is to facilitate rapid online publication as well as providing a summary of the characteristics of specific alleles .", "answer": "pharmacogenetics affects both pharmacokinetics and pharmacodynamics , thereby influencing an individual 's response to drugs , both in terms of response and adverse reactions . within the area of pharmacogenetics , findings of genetic variation influencing drug levels \n have been more prevalent , and variation in the cytochrome p450 ( cyp ) enzymes is one of the most common causes . \n much of the work concerning sequence variations in cyps aims at finding biomarkers of use for individualised treatment , thereby increasing the treatment response , lowering the number of side effects and decreasing the overall cost of treatment regimens . \n for over ten years , the human cytochrome p450 allele nomenclature ( cyp - allele ) website ( http://www.cypalleles.ki.se/ ) has offered a database of genetic information on cyp variants , along with effects at the molecular as well as clinical level . \n thus , this database serves as an assembly of past , current and soon - to - be published information on cyp alleles and their outcome effects . \n the website is used by academic researchers and companies ( eg as a tool in drug development and for outlining new research projects ) . by providing peer - reviewed genetic information on cyp enzymes , \n the cyp - allele website has become increasingly popular and widely used . \n recently , nadph cytochrome p450 oxidoreductase ( por ) , the electron donor for cyp enzymes , was included on the website , which already contains 29 cyp genes , hence por alleles are now also designated using the star allele ( por * ) nomenclature . \n although most cyps on the cyp - allele website are involved in the metabolism of xenobiotics , polymorphic enzymes with endogenous functions are also included . \n each gene on the cyp - allele website has its own webpage that lists the different alleles with their nucleotide changes , their functional consequences and links to publications in which the allele has been identified and/or characterised . \n thus , the cyp - allele website offers a rapid online publication of new alleles , as well as providing an overview of peer - reviewed data .", "id": 469} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncholelithiasis presented as chronic right back pain in the case discussed in this report . according to the clinical practice guidelines , gallbladder lithiasis is a common condition . around two - thirds of the cases\nare asymptomatic , with the most frequent clinical presentation being the presence of attacks of acute abdominal pain . however , chronic right back pain persisting for months as a main symptom is uncommon .\nthis report presents a patient with right back and subscapular pain for 9 months , demonstrating both biliary lithiasis and chronic cholecystitis .\nit is important to take into account the atypical manifestations of a prevalent illness as well as the limitations of the diagnostic tests , since the presence of gallstones can easily be missed or misinterpreted and delay in diagnosis may lead to complications which could worsen the prognosis of the patient .\na 47-year - old male presented with a history of chronic neck pain that had started 10 years back .\nhe underwent a magnetic resonance ( mr ) which showed cervical canal stenosis of degenerative etiology and also had an episode to self - limited abdominal spasmodic pain that appeared 10 years ago , considered as being functional by the gastroenterologist .\nabdominal ultrasonography was performed twice , and both times it was normal . one and a half years ago , the patient had right subscapular and paralumbar back pain at the t10l2 level for 9 months .\nhe described it as a permanent pain , which persisted throughout the day , with very intense exacerbations , especially in the evening and at night .\nthese exacerbations usually lasted for 4 - 6 h , worsening on inhalation and sometimes radiating to subcostal and right hemithorax .\nthe only feature of note on physical examination was the palpation of painful spinal processes from t10 to l2 .\nblood analysis showed the level of gamma - glutamyl traspeptidase to be 79 u / l , while all the other laboratory parameters were normal .\nabdominal computed tomography ( ct ) showed an extensive hepatic steatosis and a moderately relaxed gallbladder , with no stones observed within thin walls [ figure 1 ] .\nabdominal ct : gallbladder without gallstones despite the regular use of analgesics and the rehabilitation treatment that followed , the patient presented a torpid evolution . due to the pain in the right paralumbar area ,\nan abdominal ultrasonography was performed , which showed moderate hepatic steatosis and a gallbladder with multiple inner calculi [ figure 2 ] .\non diagnosis of cholelithiasis , a cholecystectomy was carried out , which revealed a gallbladder with a large number of yellow lithiasic structures , thereby confirming an anatomopathological diagnosis of chronic cholecystitis [ figure 3 ] .\nthe previous pain completely disappeared after surgery and the patient remained asymptomatic 7 months later .\nback pain affects 80% of adults at some point of their life and occurs at all ages .\nthe first objective is to rule out a visceral disorder or a serious potentially life - threatening condition , which occurs in 2.7% of the cases\n. back pain may be the manifestation of thoracic involvement as in esophageal disease , pleurisy , aortic aneurysm , or coronary heart disease , or an abdominal process , such as gastrointestinal ulcer , gastric cancer , pancreatic cancer , pancreatitis , or biliary pathology .\nonly one - third of the cases of gallstones are symptomatic and give an indication for surgery .\nthe most frequent symptomatic manifestation is episodic upper abdominal pain called biliary colic , with complications such as cholecystitis , acute pancreatitis , cholangitis , or choledocholithiasis being less frequent .\ncharacteristically , this pain is severe and located in the epigastrium and/or the right upper quadrant .\nthe pain may radiate to the upper back or the right scapula in 60% of the cases and might be associated with nausea or vomiting , usually occurring in the late evening or at night , in 80% of the cases .\none study carried out to characterize the presentation in cholelithiasis reported that all patients described pain in the right upper quadrant of the abdomen , including the epigastrium .\nthe pain was located in the right subcostal area ( 20% ) and epigastrium ( 14% ) , which radiated to the back in 63% .\nin fact , chronic cholecystitis is thought to be a result of a delay in diagnosis .\nthe test of choice to diagnose cholelithiasis is transabdominal ultrasound , with a sensitivity and specificity greater than 95% for detecting gallstones larger than 4 mm .\nabdominal ct scan has a very low sensitivity and gallstones may be visible due to most being isodense .\nmicrolithiasis ( stones <3 mm in diameter ) is not detectable by transabdominal ultrasonography ; however , it may cause complications such as acute pancreatitis . in some patients\nthe diagnosis can be confirmed by the detection of biliary crystals by microscopic examination of bile collected from the duodenum . in patients with a clinical history of biliary colic with negative transabdominal ultrasonography ,\nendoscopic ultrasonography is an important diagnostic tool , since it can detect microlithiasis in a proportion of patients ranging from 41 to 78% .\npatients with pain and a negative abdominal ultrasound show an endoscopic ultrasound and/or a positive analysis of the bile .\nmost of these patients show positive results on cholecystectomy , with resolution of abdominal pain and improvement in their quality of life .\nnon - vertebral causes such as the presence of gallstones should be considered in patients with back pain .\nphysicians should be aware of atypical manifestations of common diseases , so as to avoid diagnostic delays .\ngallbladder disorders should be taken into account in patients with dull , undefined right back pain , despite a normal physical examination .\nabdominal ultrasound should be chosen as the first diagnostic procedure when considering gallstones , since ct scans have a very low sensitivity for their detection . in a patient with a typical clinical report of biliary colic and a negative abdominal ultrasound ,\nthis was the case of our patient in whom the abdominal ultrasonography was normal 5 years earlier , thereby making correct differential diagnosis crucial .", "answer": "chronic right back pain is a symptom in both biliary lithiasis and chronic cholecystitis \n . ten percent of the population in the world suffers from biliary lithiasis . \n only 20% are symptomatic . \n the first diagnostic test of choice is an abdominal ultrasound . \n when a suggestive clinical sign of biliary colic with negative abdominal ultrasound is identified , we should consider the option of carrying out an endoscopic ultrasound in order to rule out microlithiasis . \n the case discussed in the report presented with chronic right back pain , which is an atypical manifestation of biliary lithiasis and chronic cholecystitis . \n it is important to know about the atypical manifestations of the prevalent illnesses as well as the limits of the diagnostic tests , in order to avoid diagnostic delays which may cause complications that could worsen a patient 's prognosis . \n this case should contribute to the medical knowledge and must have educational value or highlight the need for a change in clinical practice , especially in primary care .", "id": 470} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalthough indomethacin is usually well tolerated , some patients developed gastrointestinal side effects , specially those patients who require long term therapy\n. therefore , the use of cyclo - oxygenase-2 specific inhibitors could reduce secondary effects and they are essentially equipotent to indomethacin in vitro and in vivo .\nindeed , some reports in the literature indicate the usefulness of the cox-2 inhibitors in the treatment of indomethacin - responsive headaches [ 38 ] .\nwe report four cases of hemicrania continua and a patient suffering chronic paroxysmal hemicrania completely responsive to cox-2 inhibitors .\na 42 years - old woman had sudden onset of short - lived pains on the left side of her head .\nshe suffers for a month an intense headache with short attacks ( about 510 min ) but high frequency ( 1018 attacks per day ) .\nwe put her on indomethacin 25 mg 3 times a day , and in 24 h her hemicranial pain completely disappears . because of legs oedema we discontinued indomethacin and 1 week later the pain returned .\na 56 years - old man present with an 8 month history of a continuous left - sided headache strictly unilateral .\nthe pain was moderate in intensity but fluctuating ( between 2 and 7/10 vas ) .\nthe pain exacerbations were associated with lacrimation but not phono , photofobia , nausea or vomiting .\nan mri was normal and indomethacin 25 mg 3 times a day was started with completely recovery .\ntwo - month later he started to have gastric symptoms , indomethacin was discontinued and the hemicrania return .\na 78 years - old woman with 1 year history of continuous and strictly left - sided headache , fluctuating in intensity ( 39 in vas ) and accompanied by conjuntival injection and nasal congestion during exacerbation time .\nwith indomethacin 50 mg 3 times a day the hemicrania disappear , however , she developed disabling subjective tinnitus 1 month later .\nwe discontinued indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 18 month later .\na 64 years - old woman with 3 years history of right - sided headache , fluctuating in intensity ( 28 in vas ) .\nwith indomethacin 25 mg 3 times a day the hemicrania disappear , however , the patient suffer gastrointestinal disturbances\n. we discontinued indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 10 month later . a 76 years - old man with 6 month history of continuous left - sided headache and facial pain .\nafter 2 weeks on indometacina he complaint about pyrosis , that persists after omeprazol 40 mg per day .\nwe decided to discontinue indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 6 month later .\na 42 years - old woman had sudden onset of short - lived pains on the left side of her head .\nshe suffers for a month an intense headache with short attacks ( about 510 min ) but high frequency ( 1018 attacks per day ) .\nwe put her on indomethacin 25 mg 3 times a day , and in 24 h her hemicranial pain completely disappears . because of legs oedema we discontinued indomethacin and 1 week later the pain returned .\na 56 years - old man present with an 8 month history of a continuous left - sided headache strictly unilateral .\nthe pain was moderate in intensity but fluctuating ( between 2 and 7/10 vas ) .\nthe pain exacerbations were associated with lacrimation but not phono , photofobia , nausea or vomiting .\nan mri was normal and indomethacin 25 mg 3 times a day was started with completely recovery .\ntwo - month later he started to have gastric symptoms , indomethacin was discontinued and the hemicrania return .\nwith celecoxib 200 mg twice a day the hemicrania disappears . after 10 month\na 78 years - old woman with 1 year history of continuous and strictly left - sided headache , fluctuating in intensity ( 39 in vas ) and accompanied by conjuntival injection and nasal congestion during exacerbation time .\nwith indomethacin 50 mg 3 times a day the hemicrania disappear , however , she developed disabling subjective tinnitus 1 month later .\nwe discontinued indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 18 month later .\na 64 years - old woman with 3 years history of right - sided headache , fluctuating in intensity ( 28 in vas ) .\nwith indomethacin 25 mg 3 times a day the hemicrania disappear , however , the patient suffer gastrointestinal disturbances .\nwe discontinued indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 10 month later .\na 76 years - old man with 6 month history of continuous left - sided headache and facial pain .\nafter 2 weeks on indometacina he complaint about pyrosis , that persists after omeprazol 40 mg per day .\nwe decided to discontinue indomethacin and introduced celecoxib 200 mg twice a day with completely recovery that persists 6 month later .\nwe present five patients suffering indomethacin - responsive headache case 1 suffering from paroxysmal hemicranias and cases from 2 to 5 from hemicranias continua ( table 1 ) .\nall of them have absolutely response to indomethacin , but the presence of adverse reactions or intolerability let us discontinued and introduce celecoxib with completely recovery of the symptoms.table 1clinical characteristics of the patientscaseagegenderheadache typesidedoses ( mg)time in month142fhpleft20012256mhcleft40010378fhcleft40018464fhcright40010576mhcleft4006all doses correspond to celecoxibf female , m male , hc hemicrania continua , hp hemicrania paroxistica clinical characteristics of the patients all doses correspond to celecoxib f female , m male , hc hemicrania continua , hp hemicrania paroxistica indomethacin is consider the first - choice drug for the treatment of indomethacin - responsive headaches , and the headache resolution is consider as a diagnosis criteria in some of theses headaches .\nalthough other drugs have been reported as useful treatment , most of them are anecdotic or single cases [ 915 ] .\nother anti - inflammatory drugs that have been demonstrated as alternative drugs , in particular piroxicam , however , their efficacy is lower when compared with indomethacin .\nthe pathophysiology of theses indomethacin - response headache are still unknown , but the cyclo - oxygenase ( cox)-2 should be implicated in the pathogenesis .\ncelecoxib have been previously reported to be effective in the treatment of other indomethacin - responsive headache [ 311 ] , however , there was no absolutely response in all patients .\nanyhow , in our experience celecoxib is a good option treatment for patients suffering from hemicrania continua or chronic paroxysmal hemicranea that presents indomethacin adverse effects .", "answer": "paroxysmal hemicrania and hemicrania continua are both indomethacin - responsive headaches . \n although indomethacin use to be well tolerated , some patients developed gastrointestinal side effects . \n we report four cases of hemicrania continua and a patient suffering chronic paroxysmal hemicrania completely responsive to celecoxib . in our experience celecoxib \n is a good option treatment for patients suffering from hemicrania continua or chronic paroxysmal hemicranea that presents indomethacin adverse effects .", "id": 471} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncarbohydrates play critical roles during pollen growth and development , then in the final phase prior to dispersal carbohydrates change to prepare pollen for dispersal . following dispersal and during pollen storage , the various metabolites comprising the carbohydrate pool change in relative proportion , a behavior that is understood as an adaptation for sustaining pollen viability in time .\nsucrose in particular may be of particular importance during pollen storage , as variations among species for pollen desiccation tolerance have been linked to sucrose content .\nsucrose may replace water to preserve native protein structures and spacing between phospholipids in the plasma - membrane during dehydration .\nthe role of starch and sugars in pollen development , dispersal , and maintenance of viability has not been determined for any member of the cycadales , and is therefore a focus of needed research .\nseveral authors have conducted robust surveys and noted that starchy pollen occurred disproportionately among anemophilous species .\nrepresentatives from the cycadales were absent from these surveys and this should be corrected , as cycad pollination studies have only recently illuminated the sophisticated pollination syndromes that characterize the threatened plant group . although arthropods were collected from reproductive structures on various cycad taxa in the past , the scientific community largely ignored their potential role as pollinators due to the established belief that all cycads were anemophilous .\nthe pendulum swung in the 1980s and 1990s when extensive experimental evidence confirmed mutualisms between cycad species and specialist insect pollinators .\nmore recently , ambophily has been confirmed or proposed for several cycas species where wind has been shown to augment insect pollination .\nfurthermore , variations in aggregation tendencies and settling velocity have been reported for pollen from various cycad species .\nthis is an opportune time to add members of the cycadales to studies that have linked the relationship of pollen carbohydrates to insect versus wind pollination strategies .\nthe insect pollinators of cycads gather on male cones , where the adults socialize , mate , and use the post - dispersal male strobilus tissue as larvae food ( fig .\nthe study of idioblasts within cycad sporophyll tissues has illuminated intricacies in how general tissue chemistry may interact with pollinator feeding behaviors .\nfor zamia furfuracea , these idioblasts remained intact in the male sporophyll tissue but appeared to release their contents into female sporophyll tissue prior to ovule receptivity .\nthe authors concluded that toxins remained sequestered within the idioblasts for male tissue only , such that the pollinators could feed on parenchyma tissue around the idioblasts or consume intact idioblasts which protected insect metabolism from the toxins after consumption .\nmany but not all cycad species studied in this context exhibited similar idioblast traits . for example , cycas rumphii and stangeria eriopus strobili did not contain identifiable idioblasts .\nin contrast , macrozamia lucida and microcycas calocoma exhibited idioblast breakdown prior to pollination stage for both male and female sporophyll tissues .\nthe interactions among carbohydrates , nutrients , and toxins within cycad strobili tissues in relation to these idioblasts may prove to be of crucial importance for developing a full understanding of how pollinators feed on the plant 's reproductive tissues while enacting effectual pollination .\nconservationists in need of improved knowledge of various pollination syndromes within the cycadales will require more studies within this context . \n\nleft : microstrobilus tissue is tunneled and consumed by larvae ( arrows ) immediately after pollen dispersal .\nright : within days the entire microstrobilus is reduced to frass and pupation ( arrow ) heralds in a new generation of pollinators . the role of cycad sugars in mediating\nleft : microstrobilus tissue is tunneled and consumed by larvae ( arrows ) immediately after pollen dispersal .\nright : within days the entire microstrobilus is reduced to frass and pupation ( arrow ) heralds in a new generation of pollinators . the role of cycad sugars in mediating\nthe majority of cycad pollinators consume strobilus tissue , but direct consumption of cycad pollen may occur for some cycad pollinators . cumulative research on pollen digestion\nthe addition of cycads to studies that determine carbohydrate and nutritional quality of pollen will greatly improve this line of research whether the mutualisms represent ancient associations that pre - dated angiosperms or examples where the contemporary mutualisms were recently derived from an initial antagonistic relationship .\nthe reproductive structures of cycad species exhibit thermogenesis and volatile emissions at the time of pollination , traits that mediate pollinator behavior and maintain pollinator specificity .\nresearch is accumulating in areas such as modeling the plant behavior and parsing the influence of specific volatiles on insect behavior . enacting synchronized thermogenesis and volatile biosynthesis\nis an exceedingly expensive plant behavior , and no studies have determined the tissues of residence , quantities , and stoichiometric relations of the carbohydrate reserves that are mobilized to fund those activities .\ndroplets have been documented at the micropyle location on cycad ovules , and these droplets contain metabolites that may provide a reward for pollinators .\nstudies that marked pollinators then used deposition of the markers to track pollinator behavior have confirmed that the pollen they vector is trapped by the ovule droplets .\nthis remarkable female strobilus behavior represents a system that would be interesting to study in relation to specificity of pollinator attraction , diversity of sugar rewards , and cycad phylogeny .\ndroplets may exhibit taxon - specific carbohydrates that are suited to attracting and nourishing specific specialist pollinators .\nour recent report of fructose , glucose , and sucrose content in cycad tissues sets the stage for designing continued research on how non - structural carbohydrates are involved in cycad pollination biology . moreover , cycad horticulturists routinely harvest , store , and ship pollen prior to its use for successful pollination .\nimproved understanding of how carbohydrates and other factors influence pollen viability and longevity would improve protocols for artificial pollination .\nfinally , the risks associated with coextinctions are very real during this phase of the anthropocene , and species with complex life history traits , such as cycads , appear to be at greater risk for direct involvement in coextinctions . an increase in knowledge of how cycad carbohydrates influence successful pollination relationships may help reduce the risks of coextinctions in these mutualisms that support contemporary cycad biology .", "answer": "cycad biology , ecology , and horticulture decisions are not supported by adequate research , and experiments in cycad physiology in particular have been deficient . \n our recent report on free sugar content in a range of cycad taxa and tissues sets the stage for developing continued carbohydrate research . \n growth and development of cycad pollen , mediation of the herbivory traits of specialist pollinators , and support of expensive strobilus behavioral traits are areas of cycad pollination biology that would benefit from a greater understanding of the role of carbohydrate relations .", "id": 472} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntophi can present as a first sign of hyperuricemia but literature has limited reports as far as flexor tendon contracture presenting as a first clinical sign of gout is concerned .\nwe report a case of tophaceous gout with finger flexion contracture as its first sign .\na 45 years old man presented in our out patient department with complaint of inability to extend middle finger of his left hand along with a mass growing over volar aspect of forearm for over few months . on physical examination a firm \nhard mass around 2 * 2 cm was found over volar aspect of forearm just proximal to flexor retinaculam .\nclinical suspicion of tb tenosynovitis , was kept as a first diagnosis followed by soft tissue neoplasm and subsequently surgical exploration was performed . a whitish chalky infiltration of tendon of fds , synovial adhesion of other tendons along with median nerve embedded within hypertrophied synovium of flexor tendon noted .\npatient underwent synovectomy and excision of tendon of fds to middle finger following histo - pathological evaluation a diagnosis of tophaceous gout was made with serum uric acid level being 8.6 mg / dl .\na review of the literature reveals that gouty arthritis of the wrist is rare in isolation .\ngout at the wrist as the initial appearance of the condition occurs between 0.8 to 2% of all gout cases .\ngout occurs when serum uric acid levels are persistently higher than 6.8mg / dl . since tophaceous gout can be seen scarcely in well controlled hyper - uricaemic patient thus making preoperative diagnosis of intratendinous tophi even more strenuous .\ntophi are chalky , gritty accumulations of monosodium urate crystals that build up in soft tissue of an untreated gouty joint .\nthe peak incidence of gout is between the ages of 3050 with the prevalence increasing with age .\ntophi can present as a first sign of hyperuricemia but literature has limited reports as far as flexor tendon tophaceous infiltration presenting as a first clinical sign of gout is concerned [ 2 - 4 ] .\nwe report a rare case in which intratendinous tophaceous gout within the flexor digitorum superficialis ( fds ) tendon could not be differentiated from tubercular tenosynovitis or neoplasm preoperatively more so as it was seen in a patient with no prior history suggestive of hyperuricemia .\na 45 years old man presented in our out patient department with complaint of inability to extend middle finger of his left hand along with a mass growing over volar aspect of forearm for over 2 months [ fig 1 ] .\nthere was previous history of pain at wrist on finger movement which subsided gradually along with the decline in extension of middle finger .\nthere was no associated history of fever , loss of weight or appetite , night sweats , malaise or fatigue .\nthere was no history of trauma , pain in other joints of the body , morning stiffness of the back or hand joints , or continuous use of vibratory tools .\nhard mass around 2 * 2 cm was found over volar aspect of forearm just proximal to flexor retinaculam .\nit was non tender , non compressible , mobile at right angle to anatomical axis of forearm .\nmovement at wrist was normal with restriction of movement of middle finger in sagittal plane .\nlaboratory findings showed all within normal limits except serum uric acid which was 8.6 mg / dl .\nmagnetic resonance imaging ( mri ) showed that the mass was within the fds which on axial t1 [ fig 2 ] appeared as heterogenous isointense lesion while on coronal t2 stir [ fig 3 ] showed heterogenous mixed hypointense hyperintense lesion .\nclinical suspicion of tubercular tenosynovitis , soft tissue neoplasm and tophaceous gout was made and subsequently surgical exploration was performed .\nan incision along the flexor crease , extending further proximally while maintaining the longitudinal orientation taken . on longitudinal slit of thickened tendon sheath chalky white liquid emanated .\non futher exploration there was whitish chalky infiltration of tendon of fds [ fig 4 ] , synovial adhesion of other tendons along with median nerve embedded within hypertrophied synovium of flexor tendons . since the mass was noted well proximal to flexor retinaculam that probably could be the reason for flexor contracture and sparing of median nerve .\npatient underwent synovectomy and tenotomy of fds to middle finger because of heavy intratendinous infiltration of the tophus along with destruction of the tendinous tissue .\nhistopathological evaluation of the chalky white substance showed fibroconnective tissue showing hyalinized areas with evidence of saponification surrounded by palisades of foreign body type giant cells and chronic inflammatory cells .\nthe postoperative course was uneventful with no remarkable functional deficit from the removal of the superficialis endon to the middle finger [ fig 6 ] .\ngout at the wrist as the initial appearance of the condition occurs between 0.8 to 2% of all gout cases .\ngout patients who are not treated have a 1930% chance of developing gout in the wrist during their lifetime .\nthese nodules may not be recognized as tophi because the clinical diagnosis of gout in many instances is not straightforward . in the past reports ,\nall intratendinous infiltrations of tophaceous gout occurred at the wrist and existed with carpal tunnel syndrome .\nwe present an uncommon and unusual case of gout in the flexor tendon of forearm which occurred in isolation in a patient with no prior medical history of the recorded disease .\nmeasurement of serum uric acid level in chronic tophaceous gout may or may not be conclusive of hyperuricemia as some patients with diabetes or even alcoholics can have normal to lower levels although fnac prior to definitive intervention would have helped us to achieve the diagnosis preoperatively but rather we had gone for definitive intervention but in no way over riding the role of fnac as the procedure of choice to achieve definitive diagnosis [ 8 ] .\nsurgical intervention like tenotomy or tenosynovectomy are required to debulk tophaceous deposits , improve smooth gliding of tendon and decompress nerves but primarily medical management to treat gout remains the gold standard .\nshort - term outcomes are consistently good but the risk of rupture [ 11 ] or recurrency remain if medical control is not achieved .\na review of the literature reveals that gouty arthritis of the wrist is rare in isolation .\ngout at the wrist as the initial appearance of the condition occurs between 0.8 to 2% of all gout cases .\ngout occurs when serum uric acid levels are persistently higher than 6.8mg / dl . since tophaceous gout can be seen scarcely in well controlled hyper - uricaemic patient thus making preoperative diagnosis of intratendinous tophi even more strenuous . in indian subcontinent tubercular tenosynovitis", "answer": "introduction : tophi can present as a first sign of hyperuricemia but literature has limited reports as far as flexor tendon contracture presenting as a first clinical sign of gout is concerned . \n we report a case of tophaceous gout with finger flexion contracture as its first sign.case report : a 45 years old man presented in our out patient department with complaint of inability to extend middle finger of his left hand along with a mass growing over volar aspect of forearm for over few months . on physical examination a firm \n hard mass around 2 * 2 cm was found over volar aspect of forearm just proximal to flexor retinaculam . \n mri showed mass within tendon of fds . \n clinical suspicion of tb tenosynovitis , was kept as a first diagnosis followed by soft tissue neoplasm and subsequently surgical exploration was performed . a whitish chalky infiltration of tendon of fds , synovial adhesion of other tendons along with median nerve embedded within hypertrophied synovium of flexor tendon noted . \n patient underwent synovectomy and excision of tendon of fds to middle finger following histo - pathological evaluation a diagnosis of tophaceous gout was made with serum uric acid level being 8.6 mg / dl.conclusion : a review of the literature reveals that gouty arthritis of the wrist is rare in isolation . \n gout at the wrist as the initial appearance of the condition occurs between 0.8 to 2% of all gout cases . \n gout occurs when serum uric acid levels are persistently higher than 6.8mg / dl . since tophaceous gout can be seen scarcely in well controlled hyper - uricaemic patient thus making preoperative diagnosis of intratendinous tophi even more strenuous .", "id": 473} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nDiscovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core\n\nPaper sections:\n\nWhile M4 positive allosteric modulators (PAMs) hold great therapeutic promise for schizophrenia1\u20134 and a number of other CNS disorders,5,6 a lack of translatable chemotypes (and very limited structural diversity within known chemotypes) has hampered the field from realizing the true therapeutic potential of selective M4 activation. The area has been dominated by differentially functionalized 3-amino\u2013thieno[2,3-b]pyridine cores, typified by 1, or 5-amino-3,4-dimethylthieno[2,3-c]pyridazine such as 2 (Figure 1).7\u201316 Multiple HTS campaigns revealed similar chemotypes, with the exception of 3 and 4;17,18 however, these also failed to progress to development candidates. However, 4 (based on a 5,6-dimethyl-4-(piperidin-1-yl)thieo[2,3-d]pyrimidine core) was optimized to 5, which demonstrated exceptional CNS penetration.18 With the goal of arriving at a development candidate, we recently reported on a scaffold hopping exercise that afforded 6.19 In this Letter, we will discuss the synthesis, SAR and DMPK profiles of M4 PAMs based on a novel 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which demonstrated robust SAR beyond that of related 4\u20136, and holds promise for translation.
Recently, we performed a new functional M4 high-throughput screen (HTS) in 1536-well assay format against the ~100,000 compound Vanderbilt collection. Of the four structurally novel M4 PAMs that were identified, VU0619856 (7) represented an exciting new chemotype for the M4 field, and while related to 4 and 5, M4 PAM potency peaked at ~600 nM in these earlier series.18 New M4 PAM 7 was active on both rat and human (EC50s of 2565 nM and 897 nM respectively) with promising points of diversity. The initial strategy was to utilize an iterative parallel synthesis to explore the amide portion of the molecule followed by evaluation of the 3-cyano quinoline core. Would the 3-cyano quinoline be a quinazoline mimetic as in 5, or would SAR diverge?
The synthesis of analogs of M4 PAM 7, congeners 11 (secondary amides) and 12 (tertiary amides), was straightforward (Scheme 1), and employed a diverse collection of amines (benzyl, aryl/heteroaryl amines and secondary amines). Starting from commercial 4-chloro-6-fluoroquinoline-3-carbonitrile 8, an SNAr with ethyl piperidine-4-carboxylate provided 9 in 98% yield. After hydrolysis under basic conditions to provide the acid 10, a library of amides 11 and 12 were generated under standard HATU conditions.
While subtle improvement in potency was observed with a variety of substituted benzyl amines (11b\u2013d), compounds such as 11d had high predicted hepatic clearance, CLhep (h = 19, r = 61), and low brain distribution in rat (brain:plasma Kp = 0.29, Kp,uu = 0.26). The aniline 11e, substituted with a primary sulfonamide, showed very promising hM4 potency (248 nM, 6% ACh), but later was determined to be a P-gp substrate (MDCK-MDR1 ER = 83). Analog 11g proved to be the most potent secondary amide in the series, with an hM4 PAM potency of 147 nM; however, its DMPK profile was lacking. Importantly, this new chemotype already surpassed the PAM potency floor of 4 and 5 (hM4 PAM EC50s ~ 600 nM).
As disposition and CNS penetration were low with the secondary amides, we profiled tertiary amides to assess the impact of removing one hydrogen-bond donor. As shown in Table 2, representative tertiary amide analogs 12 suffered a diminution in hM4 PAM potency relative to secondary amides 11. However, we still advanced 12d, a 648 nM M4 PAM into in vitro and in vivo DMPK profiling. PAM 12d, like analogs 11, displayed high predicted hepatic clearance, CLhep (h = 20, r = 64), but removal of the secondary amide H-bond donor improved CNS penetration (rat brain:plasma Kp = 1.3, Kp,uu = 0.68). These data led us to generate chimeras between the new 3-cyano quinoline core and the piperidinyl ethers of 5 and explore if this structural change would bring balance to hM4 PAM potency while maintaining favorable CNS penetration.
Synthesis of the targeted chimera ligands 14 was facile (Scheme 2). Once again, commercial 4-chloro-6-fluoroquinoline-3-carbonitrile 8 underwent an SNAr reaction with 4-hydroxypiperdine to provide 13 in 90% yield. Then, a Mitsunobu reaction with various functionalized phenols and heteroaryl alcohols delivered analogs 14 in yields ranging from 10\u201380%.
As shown in Table 3, these chimeric ligands proved to possess hM4 PAM activity, but SAR was steep with few active PAMs. Of these, 14f (VU6009003) stood out as a potent hM4 PAM (EC50 = 197 nM, pEC50 = 6.78 \u00b1 0.17, ACh Max = 79\u00b1 10). Prior to deeper characterization of 14f, we elected to survey the necessity of the 3-cyano quinolone core, and assess if deletion of the 3-CN moiety, or additional functionalization of the quinoline core would afford hM4 PAMs for further evaluation. To assess this possibility, analogs 17 were readily prepared in two steps from commercial 15 and 5-fluoro-2-methlypyridine via an SNAr reaction to provide, after Boc deprotection 16. A second SNAr reaction with various 4-halo quinolines produced analogs 17.
Deletion of the 3-CN moiety as in 17a led to a greater than 10-fold loss in hM4 PAM potency, highlighting the necessity of this novel moiety. Moreover, this result suggests that the 3-CN moiety in this core is not bioequivalent to the nitrogen of the quinazoline-based hM4 PAMs represented by 5. Replacement of the 6-fluoro moiety with either a 6-Cl atom (17b, hM4 PAM EC50 = 905 nM) results in a ~4-fold loss of potency, while replacement with a methyl group (17c, hM4 PAM EC50 = 3018 nM) results in a ~15-fold loss in hM4 PAM potency relative to 14f. Of these analogs 17, only a 6,8-difluorocongener 17e, proved of equivalent potency to 14f.
Thus, 14f (VU6009003) emerged from this effort as a novel M4 PAM worthy of further profiling. PAM 14f was potent at both human M4 (197 nM, 80% ACh Max) and rat M4 (437 nM, 74% ACh Max) with very modest species difference in PAM potency, and a marked improvement over the HTS hit 7. In terms of physicochemical properties, 14f was a low molecular weight compound (MW =362) with an attractive xLogP (2.83) for a CNS agent (Table 5). In a microsomal intrinsic clearance assay, 14f displayed moderate clearance in both species (predicted human CLhep = 15 mL/min/kg, predicted rat CLhep = 52 mL/min/kg) with moderate fraction unbound in human plasma (fu = 0.024), rat plasma (fu = 0.031) and rat brain (fu = 0.014). In our standard rat plasma:brain level IV cassette paradigm, 14f showed excellent CNS penetration with a rat brain:plasma partitioning coefficient (Kp) of 5.3, and when corrected for fraction unbound in plasma and brain, a Kp,uu of 2.4. We also assessed human P-gp efflux potential in a MDCK-MDR1 transwell assay, and found no P-gp liability (ER = 1.1) coupled with high passive permeability (Papp = 28 \u00d7 10\u22126 cm/s). In vivo, 14f displayed lower clearance (CLp =36 mL/min/kg) in rat (IV PK cassette, 0.2 mg/kg) than predicted (CLhep = 52 mL/min/kg), with a short t1/2 (1.7 hours) and moderate volume (Vss = 3.2 L/kg). In a dog IV PK cassette study (0.2 mg/kg), 14f displayed clearance (CLp = 41 mL/min/kg) at hepatic blood flow with a t1/2 of 1.6 hours (likely as a consequence of moderate-to-high volume, Vss = 4.0 L/kg); however, 14f did display a reasonable IVIVC with predicted hepatic clearance in dog (CLhep = 27 mL/min/kg) and good fraction unbound (fu = 0.045). While attractive overall in terms of novel chemotype, favorable CNS MPO score (>5),21 fraction unbound and CNS penetration, the disposition of 14f remains to be addressed (after a deeper understanding of metabolic soft spots).
In summary, an HTS campaign identified a new M4 PAM chemotype 7, related to 4 and 5, but displaying distinct SAR, improved M4 PAM functional potency and enhanced CNS penetration. The discovery of new M4 PAM chemical matter is of critical importance to enable translation to the clinic, as the field has been largely dominated by limited chemotypes 1 and 2, fraught with development challenges. Metabolite identification studies and further optimization efforts are underway and will be reported in due course.
", "answer": "This Letter details the discovery and subsequent optimization of a novel M4 PAM scaffold based on an 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which represents a distinct departure from the classical M4 PAM chemotypes. Optimized compounds in this series demonstrated improved M4 PAM potency on both human and rat M4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain:plasma Kp = 5.3, Kp,uu = 2.4; MDCK-MDR1 (P-gp) ER = 1.1).", "id": 474} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmultiple carcinoid tumors of the small intestine are rare and are very difficult to detect preoperatively .\na 75-year - old woman in whom the bleeding focus could not be found by upper and lower endoscopy and abdominal ct was admitted for evaluation of anemia .\nwe examined the patient with total double - balloon endoscopy ( dbe ) and located multiple submucosal tumors .\nwe report a case of a successful laparoscopic operation for multiple carcinoid tumors in the small intestine without intraoperative endoscopy . total digestive tract observation using dbe\ntumors of the small intestine account for 1% to 2% of all gastrointestinal neoplasms ( only 0.3% of all neoplasms ) .\nhowever , the incidence of small intestine cancer has increased dramatically over the past 30 years , and the increase in carcinoid tumors has been largely responsible .\ncarcinoids of the ileum account for 15.4% of all gastrointestinal carcinoids and are multicentric in 2030% of patients .\nthe lack of signs and symptoms , lack of definitive preoperative diagnostic tests , and the variable efficacy of available tests make small intestine tumors difficult to diagnose .\nthe recent development of capsule endoscopy ( ce ) and double balloon endoscopy ( dbe ) has improved diagnostic capabilities for the small intestine .\nwe report the first case of multiple carcinoid tumors of the small intestine preoperatively diagnosed by dbe and treated with laparoscopic surgery .\na 75-year - old woman was referred to our hospital with melena and severe anemia ( hemoglobin ( hb ) 7.2 g / dl ) . she had a history of stroke at age 59 years , and was being treated with antiplatelet therapy at the time of admission to the referring hospital . at that hospital ,\nthe source of gi bleeding was not revealed by upper and lower gastrointestinal endoscopy examination , abdominal computed tomography ( ct ) , or ultrasound ( us ) . through radiological enteroclysis ,\nan elevated lesion was found in the ileum , which was suspected to be a submucosal tumor and measured 15 mm in diameter .\nafter 2 months at the referring hospital , she was admitted to our hospital for a thorough investigation of the small intestine .\nphysical examination revealed her abdomen to be soft and flat without any pain or tenderness .\nresults of blood tests were as follows : hb 11.3 g / dl ( normal : 11.115.2 g / dl ) , red blood cell count 418 10/ml ( normal : 380540 10/ml ) , and hematocrit 35.3% ( normal : 35.645.4% ) .\nwe then examined the patient with peroral dbe ( en-450p5 : fujifilm medical co. , ltd . ,\na tumor was located about 250 cm from the ligament of treitz and measured 8 mm in diameter ( figure 1 ) .\nhistologic examination of the biopsy sample obtained by endoscopy confirmed the diagnosis of a carcinoid tumor .\nthe tumor was composed of small uniform epithelial cells , which stained positively for chromogranin a and synaptophysin .\nanother tumor detected through peranal dbe was located about 110 cm from the ileocecal valve and measured 15 mm in diameter .\nalso , other small tumors were detected that measured 3 mm and 5 mm in diameter and had a relatively smooth surface , similar to a submucosal tumor .\nthese small tumors were diagnosed as carcinoid tumors by endoscopic findings , whereas histologic examination could not make this diagnosis . the largest tumor had ulcerations , which could account for the gi bleeding ( figure 2 ) .\nthe patient underwent partial resection of the small intestine by laparoscopic surgery ( resected portion : 23.8 cm ) .\nshe had already undergone a preoperative total small intestinal examination using dbe ; therefore , it was not necessary to perform intraoperative endoscopy .\nthe resected specimen contained tumors measuring 1410 mm , with central ulceration ( figure 3 ) , 2.86 mm and a tumor 3 mm in diameter .\nmicroscopically , the tumors were composed of small uniform epithelial cells ( figure 4b ) , which stained positively for chromogranin a and synaptophysin ( figure 5 ) .\nno metastases were found in the regional lymph nodes , and the surgical margins were negative for tumor cells .\nfollow - up dbe was performed 18 months later , and there was no sign of recurrence in the small intestine .\nthis is the first report of laparoscopic surgery without the use of intraoperative endoscopy for multiple carcinoid tumors of the small intestine , which was possible because the tumors were diagnosed before surgery by dbe .\ncarcinoid is the second most common malignancy , accounting for approximately 2025% of all small intestine lesions .\ncarcinoid tumors are more common in the ileum ( most within 60 cm of the ileocecal valve ) than in the jejunum or duodenum , and lesions may be multiple and/or metastatic ( liver and lungs ) at the time of diagnosis because one fourth of carcinoid tumors in the small intestine are multiple . on the guideline , by far the majority of small intestinal neuroendocrine tumors ( nets , including carcinoid ) are malignant in nature . whether liver metastases are present or not , resection of the primary tumor is appropriate to cure or to delay progression that would otherwise endanger the small bowel .\ncarcinoids of the rectum , stomach , and duodenum generally are found by endoscopy at an early stage , whereas carcinoid tumors of the small intestine usually are discovered after resection of the small intestine for symptoms of obstruction or during exploration of the small intestine in search of a primary tumor after distant metastases have been found [ 2,912 ] . through conventional imaging techniques ( e.g. ,\nct , us , double contrast barium study ) , few tumors of a small diameter are identified .\ncurrently , with advancement in methods of ce , small intestine tumors can be located .\nce had a high diagnostic yield of 45% for identification of primary small intestinal carcinoid tumors .\nhowever , it remains purely a diagnostic procedure at present because it is not suitable for histological diagnosis and procedures .\nfor this reason , if laparoscopic surgery is performed in a patient who was diagnosed as having multiple carcinoid tumors of the small intestine , it is usually necessary to perform intraoperative endoscopy to confirm that the lesion is a carcinoid tumor .\nit is notable that in reporting the results of their study , m. bellutti et al .\nsuggested that intraoperative endoscopy is a potential gold standard for nets . on the other hand\na submucosal tumor of the ileum or the jejunum was detected by dbe in 7 of 12 patients ( 58% ) with suspected carcinoid syndrome .\nin addition , tumor marking using injection of ink for the exact location during dbe has been helpful for subsequent operations , especially for laparoscopic resection . by utilizing dbe\n, we were able to locate the multiple ileal tumors and to perform laparoscopic surgery without intraoperative endoscopy in the patient reported here .\ndbe is a safe procedure , with low complication rates even when therapeutic maneuvers are performed .\nas only dbe allows direct , controlled visualization of small intestine tumors and their histological confirmation preoperatively , it may be considered the gold standard for the diagnosis of such tumors .\ndbe is extremely useful to detect and diagnose asymptomatic small lesions in the small intestine .\nbased on the case presented here , we recommend total digestive tract observation using dbe before performing laparoscopic operation for multiple tumors of the small intestine .", "answer": "summarybackgroundmultiple carcinoid tumors of the small intestine are rare and are very difficult to detect preoperatively.case reporta 75-year - old woman in whom the bleeding focus could not be found by upper and lower endoscopy and abdominal ct was admitted for evaluation of anemia . \n we examined the patient with total double - balloon endoscopy ( dbe ) and located multiple submucosal tumors . \n the multiple carcinoid tumors were resected successfully under laparoscopy.conclusionswe report a case of a successful laparoscopic operation for multiple carcinoid tumors in the small intestine without intraoperative endoscopy . \n total digestive tract observation using dbe is very useful for laparoscopic operation for multiple tumors in the small intestine .", "id": 475} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhowever , cost , difficulty of implementation , and other barriers impede adoption of such systems , and studies have documented low rates of technology acquisition and implementation in emergency department ( ed ) and other settings .\na study of residency - affiliated eds in 2000 found low rates of adoption , with only 7% reporting fully implemented technology for medication error checking , 18% for computerized medication order entry , and 21% for clinical documentation .\na 2006 survey of health information technology in all massachusetts eds found similar results , with 11% of respondents reporting fully implemented technology for medication error checking .\nanother national study showed that , during 20012003 , only 31% of us eds used electronic medical records in any form .\nour hypothesis is that fewer than half of us eds had adopted electronic health records systems and related decision - support tools by 20052006 .\nwe report on data collected as part of the national ed safety study ( nedss ) .\nwe recruited eds mainly by inviting network members . since most members are affiliated with an emergency medicine residency program ( i.e. , are academic eds ) , we also recruited non - academic and other eds not affiliated with emnet through postings on emergency medicine list servers , by contacting sites directly , and through presentations at emergency medicine meetings .\nfor the parent national ed safety study , each site had a site responsible investigator .\nthe survey asked about ed attributes and adoption of the health information technology applications shown in table 1 .\nthese applications were chosen by the authors as representative of the diverse applications available today , within the constraints of a larger survey with other goals .\nwe performed all calculations with sas 9.12 ( sas institute , cary , nc ) .\ntable 1characteristics of 68 emergency departments surveyedcharacteristicn ( % ) median computerization scoreemergency medicine residency affiliation yes51 ( 75%)9 no17 ( 25%)8annual census ( visit per year ) < 10,0000n / a 10,00019,9990n / a 20,00029,9991 ( 1%)5 30,00039,99912 ( 18%)8.5 40,00049,99912 ( 18%)7.5 50,00043 ( 63%)9us region northeast30 ( 44%)8 midwest15 ( 22%)9 south10 ( 15%)9 west13 ( 19%)8we surveyed key informants at 69 us eds , as part of the national emergency department safety study , with 68 ( 99% ) of eds surveyed respondingthe computerization score was simply a way for us to count the number of information technologies that had been acquired .\nwe calculated the score by assigning one point for each acquired application listed in table 2 characteristics of 68 emergency departments surveyed we surveyed key informants at 69 us eds , as part of the national emergency department safety study , with 68 ( 99% ) of eds surveyed responding the computerization score was simply a way for us to count the number of information technologies that had been acquired .\nwe calculated the score by assigning one point for each acquired application listed in table 2 our main outcome measure is descriptive : how many eds have adopted which applications ?\nour secondary objective was to determine whether ed characteristics predicted adoption of health information technology .\nfirstly , we selected one application that seemed to represent the potential of information technology to improve health care .\nthere is substantial debate about what constitutes meaningful use of information technology , and we felt that selecting one crucial application for analysis would be the best way to compare across eds . for the purpose of this analysis , we selected computerized medication ordering as the application .\nwe chose this application because medication ordering represents a crucial site of potential intervention to improve adherence to recommended care and avoid error .\nwe studied this as an outcome variable by creating a logistic regression model with computerized medication order entry as the dependent variable .\nwe categorized eds according to emergency medicine residency affiliation ( binary ) , annual census ( continuous ) , and region ( categorical : northeast , midwest , south , and west ) .\nwe used multiple logistic regression to model these characteristics as predictors of adoption of computerized medication ordering .\nwe used the hosmer - lemeshow goodness of fit test to evaluate for non - linearity .\nsecondly , we did not wish to limit our investigation to any one application or combination of applications , as was done in the analysis described above .\nthus , we also compared eds by the raw number of applications they had adopted .\nwe accomplished this by creating a computerization score , as was done in a prior study .\nthis score is simply a count of applications , with one point assigned for each acquired application .\nwe then used multiple linear regression to predict computerization score by the above ed characteristics and planned to consider any characteristic to be a \nsignificant predictor of the computerization score if the p - value of its beta coefficient was 0.05 . we used the sas spec option to assess for heteroscedasticity and inspected residual plots for qualitative evidence of a relationship .\nof 69 eds surveyed , 68 ( 99% ) in 23 us states completed the survey .\nthe participants were generally large urban academic eds , with 44% located in the northeast .\ntable 2 shows the number and proportion of eds reporting availability of selected health information technologies .\ncomputerized physician order entry , clinical decision support , and bar coding technology were present in fewer than 40% of eds .\nin contrast , some other applications were present in most of the eds surveyed , including laboratory test ordering and results , notes from prior encounters , and ecg results .\nthe right - hand column of table 1 shows the computerization score ( see methods ) , stratified by ed characteristics . \n\ntable 2information technology in 68 us emergency departmentsinformation technology applicationnumber ( % ) of eds reporting availability of each applicationcomputerized physician medication order entry26 ( 38%)clinical decision support for medication allergies13 ( 19%)clinical decision support for drug - drug interactions9 ( 13%)outpatient notes39 ( 57%)inpatient notes43 ( 63%)surgical notes53 ( 78%)prior ed visit notes54 ( 79%)laboratory results66 ( 97%)laboratory test ordering39 ( 57%)test ordering other than laboratory tests42 ( 62%)radiology results67 ( 99%)ekg results62 ( 92%)patient tracking50 ( 74%)bar coding for patient , medication , or sample identification14 ( 20% ) information technology in 68 us emergency departments our analysis of ed characteristics did not reveal any significant variation in availability of electronic medication ordering or computerization score , by emergency medicine residency affiliation , annual census , or region .\nbusinesses from restaurants to banks and airlines rely on such technology to process information that has much in common with medical information .\nwhy , then , would our nationwide sample of eds reveal that only 19% have the capability to check a medication order to see if the patient has a documented allergy to that medication ?\nreasons might include apprehension . in the enthusiasm to promulgate the spread of health information technology , the downsides are often under - emphasized .\nthe present report echoes the findings of the three prior studies of health information technology adoption in us eds \nonly two of these prior studies assessed the adoption of individual applications , such as computerized physician order entry .\none was a survey of us emergency medicine residency - affiliated eds in 2000 , and the second was a survey of all massachusetts eds in 2006 .\nour ability to conduct direct quantitative comparisons across time is limited , because different eds participated in the surveys .\nall three studies revealed that a minority of eds had computerized medication ordering : 38% in the present national study , 15% in the 2006 ma study , and 18% in the 2000 national study .\nquantitatively , the increase from 18% to 38% might indicate wider dissemination of these technologies , or might be due to sampling variation .\nqualitatively , it seems reasonable to conclude from these three studies that most us eds do not have electronic medication ordering , or its companion technology , medication error checking .\nhowever , this conclusion must be caveated by the fact that large academic eds were over - represented in these samples .\nstudies of health information technology adoption in physicians offices and hospitals throughout the country also revealed slow uptake by 2008 [ 8 , 9 ] .\nthese studies found that only 7.6% of us hospitals have a basic electronic records system , and 1.5% a comprehensive one .\n( these studies defined basic as including only demographic information , cpoe , laboratory and imaging results , and comprehensive as including the above , plus clinical notes , plus electronic prescribing , radiographic image display , and decision support . )\nonly 4% of physicians offices have a fully functional electronic - records system , and 13% have a basic system .\ned - based studies also show that some health information technology applications are widespread , including patient tracking ; ordering tests ; and displaying prior visit notes , ecgs , and laboratory and radiology results [ 2 , 3 , 5 ] .\nan analysis of the types of health information technology may improve our understanding of these results .\none type of application is computationally simple , merely entering and extracting information from a database , and displaying it .\nthe other type of application requires all of the above processes , plus algorithmic processing that seeks to supplement human cognition with computation . for lack of better terms\n, we might refer to these two types of application as passive and active applications , respectively . from a workflow standpoint ,\nsuch technologies include patient tracking ; ordering tests ; and displaying prior visit notes , ecgs , laboratory and radiology results .\nactive applications add functions designed to improve outcomes by reducing error or increasing adherence to the standard of care they seek to change human behavior .\nthese applications often embody fundamental changes in clinical processes , and implementation is intertwined with changes in workflow [ 6 , 10 ] .\nexamples include computerized provider order entry and related error - checking functions , and decision support systems . in light of this dichotomization\n, we can see that the present and prior studies reveal a high rate of adoption of passive applications in us eds and a low rate of adoption of active applications [ 2 , 3 ] .\n( we included laboratory test ordering in the passive category for historical reasons .\nsuch systems have been present in most eds for many years and were not originally subject to behavior - modification technology . ) an optimistic interpretation of our data would be to celebrate the fact that most us eds did not invest in expensive , cumbersome , and even potentially risky systems prematurely . now that a large number of commercial and home - grown systems are available , we should take the time to study them and reach consensus on which would be best for particular environments .\nwe should pay particular attention to the interaction of information systems with human workflows [ 6 , 10 ] .\nthe certification commission for healthcare information technology formed an ed work group in 2007 , which is in the process of certifying various health information technology platforms for ed use , in concert with the health level seven project .\nthis type of certification process may be an important first step in improving the types of systems that are available , or at least our understanding of what is available .\nparticipating sites were generally large , urban , academic eds . because the underlying patient safety study focused on adult illnesses , the study excluded children s hospitals .\nwe did assess for variability in technology adoption by ed characteristics , and found no significant variation .\nthis improves our confidence in the generalizability of our data to other eds in the us , though , again , large academic eds were over - represented in the sample .\nperhaps more saliently , the present results are similar to those of prior studies , from academic eds throughout the us , and all eds in massachusetts .\nit remains true that we have little data on health information technology adoption in the 1/3 of us eds with an annual visit volume < 10,000 .\nfrom the perspective of the individual patient , small eds have the same clinical goals as large eds .\nbut from a systems perspective , the marginal cost of health information technology in low - volume settings will be high relative to benefit , both financially and in terms of workflow modification and associated risks .\nanother limitation is the fact that our assessment was part of a larger survey , and thus , we could not conduct as detailed an inquiry as would have been desirable . in particular , we did not ascertain adoption of health information technology for medication order checking or decision support .\nhowever , the low rate of adoption of medication order entry technology allows us to conclude with confidence that these technologies were not available in the majority of respondent eds .\nactive applications involve intertwining of technology and human workflows , and are intended to change behavior .\ntogether with the findings of other studies , our results demonstrate that most us eds have adopted passive applications but not active applications that have been recommended forcefully [ 2 , 3 ] .\nwe view this as an opportunity , because careful analysis of available platforms and the pitfalls in their implementation may result in better outcomes and less difficulty in the implementation process .\nthe ideal forum for such analysis remains unclear , though the certification commission for healthcare information technology ed work group is a notable effort .", "answer": "backgroundinformation technology may improve patient safety , and is a focus of health care reform . \n a minority of emergency departments ( eds ) in massachusetts , and in academic eds throughout the us , have electronic health records.aimsassess health information technology adoption in a nationwide sample of eds.methodswe surveyed 69 us eds , asking site investigators about the availability of health information technology in 20052006 . using multiple linear regression , we compared adoption of technology by ed type ( emergency medicine residency affiliation , annual census , us region ) to assess generalizability of the findings.resultssixty-eight eds ( 99% ) provided information about health information technology ; 75% were affiliated with an emergency medicine residency , and all were urban . \n most respondents had applications that simply relay information from one place to another , including patient tracking ( 74% ) ; ordering tests ( laboratory 57% , others 62% ) ; and displaying prior visit notes ( 79% ) , ecgs ( 92% ) , laboratory ( 97% ) , and radiology ( 99% ) results . \n a minority had more - advanced applications , which seek to modify human behavior , including medication ordering ( 38% ) , allergy warnings ( 19% ) , and medication cross - reaction warnings ( 13% ) , and a few used bar coding ( 20% ) . \n there were no significant differences in technology adoption by ed type.conclusionsthis and prior studies suggest that some applications particularly those relevant to modifying clinician behavior are not widespread in us eds , while others are . \n the reasons for this are unknown , but might include expense and unintended consequences . \n the fact that the emergency medicine community has not rushed to adopt certain applications presents challenges and opportunities .", "id": 476} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe lingual tonsils develop at 6.5 weeks between the second and third arches ventrally while palatine tonsils develop at 8 weeks from second pouch ( ventral and dorsal ) .\ntonsils are predominantly b - organs and b - lymphocytes comprise 5060% of tonsillar lymphocytes .\nample evidence shows that tonsils are involved in inducing secretory immunoglobulin production [ 4 , 5 ] .\nboth adenoids and tonsils are favourably located to mediate immunologic protection of the upper aerodigestive tract as they are exposed to air borne antigens .\ntonsils are particularly designed for direct transport of foreign material from the exterior to the lymphoid cells .\ninvolution of the tonsils begins after puberty , resulting in a decrease of the b cell population and a relative increase in the ratio of t to b cells .\nthe commonest indication for tonsillectomy is recurrent tonsillitis , which results in shedding the immunologically active cells and decreasing antigen transport function with subsequent replacement by stratified squamous epithelium [ 6 , 7 ] .\nwe investigated the common pathogens causing this condition in our hospital and report here our findings .\npatients presenting at our clinic with signs and symptoms of chronic tonsillitis were enrolled for the study .\nthe study was explained to them and where children were involved , to their parents .\nbefore the operation began , the laboratory was informed and a technician stood by to collect the tonsil as soon as it was removed .\nsterile wide - mouthed container was provided and the excised tonsils were aseptically put into them and carried immediately to the laboratory for processing .\nas soon as the tonsil reaches the laboratory , it is cut into two with a sterile surgical blade ; the inner surfaces were swabbed with sterile cotton swab , and inoculated onto two blood agar plates , one macconkey agar and one chocolate agar plate .\none blood agar plate was incubated anaerobically , the chocolate plate in 510% co2 while the rest of the plates were incubated aerobically .\nthe aerobic plates and the co2 plate were examined after 24 hours ; if no growth , they were reincubated for a further 24 hours after which if still no growth , they were discarded as negative .\nthe anaerobic cultures were examined at 72 hours and if no growth they were reincubated for a total of 7 days .\nthere were 34 bacterial isolates from 52 patients , giving a percentage positivity of 65.38% .\nthirty isolates were gram - positive bacteria and only four were gram - negative , made up of two genera , klebsiella and pseudomonas .\nstaphylococcus aureus was the predominant isolate ( 15/34 , 44.1% ) , followed by group b streptococcus ( 12/34 , 35.3% ) .\nothers were , streptococcus pyogenes ( group a streptococcus ) , 1/34 , 2.94% ; and untypable streptococcus spp . 2/34 , 5.88% .\nthe gram - negative bacteria consist of klebsiella pneumoniae 3/34 , 8.82% and pseudomonas aeruginosa 1/34 , 2.94% ( table 1 ) .\nthere were no growths in 7 patients while 11 yielded growth of normal flora only .\nall the cases were chronic and most of them took antibiotics before presenting to us .\nthe ratio of anaerobic to aerobic bacteria in saliva is approximately 10 : 1 because of variations in oxygen concentration throughout the oral cavity . invargsson et al . revealed that streptococcus pneumoniae was recovered in 19% of healthy children , hemophilus influenzae in 13% , group a streptococcus in 5% , and moraxella ( branhamella ) catarrhalis in 36% .\nthe frequency of pathogens decreases with age , possibly because of increased immunity . because the oropharynx is colonized by many organisms , most infections of wadeyer 's ring are polymicrobial . in our study ,\nbut in contrast with other researchers who found beta - hemolytic streptococci to be the predominant isolate [ 14 , 15 ] .\nthese authors also found that streptococcus pyogenes was isolated more frequently in recurrent tonsillitis while in the tonsillar hypertrophy , streptococci beta - hemolytic non a group predominated .\nit has been suggested that fine - needle aspiration can be used in identifying tonsil core bacteriology in clinical settings .\nmethicillin resistant staphylococcus aureus ( mrsa ) , has been isolated from the surface and core tonsils in children .\nwe did not encounter any mrsa in our study ; and all the staphylococcus aureus isolated were sensitive to augmentin and vancomycin .\nit would appear from our results , that augmentin should be our drug of choice in future treatment of tonsillitis from this centre .\nthe findings of kuhn et al . supported the etiologic role of hemophilus influenzae and staphylococcus aureus in hypertrophic tonsils with or without inflammation [ 18 , 19 ] .", "answer": "objectives . tonsillitis is a common infection in all age groups , especially under the age of five . organisms causing this condition vary from place to place . \n our aim is to find out the main causative agents of this condition in our hospital . \n patients and methods . \n fifty - two consenting patients who needed tonsillectomy in khamis civil hospital , kingdom of saudi arabia , between september 2006 and april 2007 , were enrolled for the study . \n swabs were taken from their inner surfaces and cultured for anaerobes and aerobes according to standard microbiological techniques . \n results . \n fifty - two patients , consisting of 30 males and 22 females were enrolled . \n their mean age was 9.81 6.47 . \n nearly 65% of patients had positive cultures while 35% were negative . \n the commonest bacteria isolated were staphylococcus aureus ( 44.1% ) ; and group b streptococcus ( 35.3 % ) . \n two gram - negative bacteria , klebsiella pneumoniae , ( 8.82% ) , and pseudomonas aeruginosa ( 2.94 % ) , were also isolated . \n no anaerobe was isolated . \n conclusion . \n gram - positive cocci , consisting of staphylococcus aureus and group b streptococcus ( streptococcus agalactiae ) , are the major causes of tonsillitis requiring surgery in our hospital . \n antibiotic treatment of this condition should be directed largely against these organisms .", "id": 477} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthird molar impaction is the most commonly observed tooth impaction in modern communities , as the third molars are the last teeth to erupt .\nthird molars have been reported to account for 18 - 32% of impactions . while most studies have reported no gender differences in caucasians ,\nthe purpose of this study was to investigate the prevalence , distribution , position , and depth of impacted third molars ( itms ) in turkish orthodontic patients from a single academic institution .\nwe retrospectively reviewed the panoramic radiographs , intraoral photographs , and dental casts of 207 patients ( 62 men and 145 women ; age , 20 - 39 years ; mean age , 22.7 3.29 years ) who had undergone orthodontic treatment .\npatients with conditions such as cleidocranial dysplasia , and down 's syndrome were excluded from the study . if an itm was present , its angle and depth of impaction were recorded .\nif the third molar was not fully erupted to its normal functional position or the eruption process was not complete with regard to angular position or lack of space , then it was deemed as impacted .\nthe angulation of impaction was measured with reference to the angle formed between the intersected longitudinal axes of the second and third molars .\nthe following classification system was adopted : 0-10 , vertical ; 11-79 , mesioangular or distoangular ; 80-100 , horizontal , and the remaining cases were classified as cases of inverted or buccolingual impaction .\nthe level of impaction was considered in relation to alveolar bone and the cementoenamel junction of the itm : level a , not buried in bone ; level b , partially buried in bone ( if any part of the cementoenamel junction was lower than the bone level , the tooth was considered to be partially buried in bone ) ; and level c , completely buried in bone .\nstatistical analysis was performed using ncss ( number cruncher statistical system ) 2007 statistical software ( utah , usa ) .\ngroups were compared using pearson 's chi - square test and fisher 's exact test .\nin our orthodontic patient population , itms were evident in 112 patients ( 54.1% ) .\nprevalence of itm was not found to be significantly different between men and women ( 61.3% , n = 38 vs. 51.0% , n = 74 , respectively ) , ( p = 0.23 ) .\nthe proportion of itms was approximately equally represented in the maxilla and the mandible for both genders . of the 300 itms ,\nthere was no significant difference between the distribution of maxillary and mandibular itms in men and women ( p = 0.97 ) .\nin addition , there was no significant difference in the frequency of third molar impaction between the right and left sides within each arch ( p > 0.05 ) .\nthe distribution of itms on the right and left sides was equal ( 50% ) in the mandible . in the maxilla , the distribution was 51.35% for the right side and 48.65% for the left side .\ndistribution of itms by arch and gender the distribution of patients by number of itms is shown in table 2 .\nthe most common type was impaction of all 4 third molars and 2 third molars .\nthere were no significant differences between the distribution of the number of itms in male and female patients ( p > 0.05 ) .\ndistribution of patients by total number of itms the occurrence of the different angulations of impaction in the mandible is shown in table 3 , and their occurrence in the maxilla is shown in table 4 .\nthe most common angulations were mesioangular ( 65.1% ) and horizontal ( 25.7% ) in the mandible , while they were distoangular ( 64.2% ) and vertical ( 23.6% ) in the maxilla .\nthe distribution of the mesioangular and horizontal angulations of impaction in the mandible were significantly different between the men and women ( p < 0.05 ) [ table 3 ] . in the mandible , the mesioangular position was more common among women than among men , while this association was vice versa with respect to horizontal position .\non the other hand , there was no significant difference in the frequency of different angulation types of impaction between the sexes in the maxilla .\ndistribution of angulations of mandibular itms distribution of angulations of maxillary itms the distribution of impaction levels is shown in table 5\nthere were no significant differences between level b and level c impactions in the maxilla ( p = 0.75 ) , or in the mandible ( p = 0.79 ) in men and women .\nthe relative proportion of the different levels of impaction was significantly different between the 2 arches .\nthere was significantly more level c impaction in the maxilla ( 46% ) than in the mandible ( 32% ) ( p = 0.02 ) .\nthere was no significant difference between level b and level c impactions in the maxilla or the mandible , in men ( p = 0.45 ) , or women ( p = 0.21 ) .\ndistribution of levels of impacted third molars in the maxilla and mandible in our patient population , 86 patients presented with bilateral impaction ( 76.8% of all subjects with itms ) [ table 6 ] . the frequencies of maxillary and mandibular bilateral impaction were similar ( 30.2% , and 24.4% , respectively ) .\nseventy - one percent of the mandibular bilateral impaction cases and 82% of the maxillary bilateral impaction cases presented with the same angle classification and the same level of impaction [ table 7 ] .\nbilateral impaction with the same angulation ( 82% ) was significantly more frequent than bilateral impaction with different angulation ( 30% ) at the same level of impaction in the maxilla ( p = 0.00 ) .\nthere was no significant relationship between the impaction levels with regard to mandibular bilateral impactions ( p = 0.12 ) .\nthere was also no significant relationship between the bilateral impaction angulations in the maxilla and the mandible ( p = 0.38 ) .\ndistribution of bilateral impaction by arch distribution of bilateral impaction by angulation and level in the maxilla and mandible\nto achieve more reliable results in this study , 20 years was deemed to be the lower age limit on the basis of literature regarding the growth and eruption time of the third molars .\nin addition , due to possible angulation changes of third molars even after 30 years of age , the upper age limit was 39 in our patient population .\nalthough all of the patient records and file information were carefully investigated , it is still possible that some third molars may have been extracted . for determination of the angular position of an itm ,\nthis useful system has also been used before by other researchers . in many other studies ,\nthe angulation of itms was usually determined using visual impression based on winter 's classification . due to ethnic variations\n, differences in diet , and genetic heredity , variations in jaw - tooth sizes and facial growth can occur .\nthus , some differences are evident in the prevalence of itms in studies of different populations . in addition\n, differences in diagnostic criteria , sample sizes , and statistical methods may also lead to differences in results . in our study ,\nmany other studies have reported much lower frequencies of itms . in another turkish population study ,\nit was concluded that the prevalence of itms was 35.9% , and this proportion was lower than was observed in our study . on the other hand , saglam and\ntuzum reported the frequency of lower third molar impaction to be 42.4% and that of upper third molar impaction to be 40.5% in a sample of turkish patients aged between 16 and 75 .\nthere were some methodological differences between these studies with regard to factors such as age limits .\nsome other prevalence studies have also reported higher itm frequencies , between 65.6% and 76.0% , in american , chinese , indian , and swedish populations .\nwe observed no significant gender differences with regard to the frequency of third molar impactions ( p = 0.23 ) .\nhowever , some other studies , including another investigating a turkish orthodontic patient population , have reported a significantly greater frequency of itms in women ( p < 0.05 ) . in our study , the proportions of impacted mandibular ( 50.7% ) and maxillary ( 49.3% ) third molars were almost equal .\nin contrast , in most other studies , itms were observed more frequently in the mandible than in the maxilla , although some studies have also indicated the opposite .\nbecause of the different classification systems used in different studies , including classification determined solely by visual impression alone , it is difficult to make reliable comparisons of the reported itm angulations . in this study\n, we found that mesioangular impaction of mandibular third molar and distoangular impaction of maxillary third molar were the most common ( 65.1% , and 64.2% , respectively ) .\nmost other researchers have also reported that mesioangular inclination was the most common , in the mandible . however , hugoson and kugelberg reported vertical impaction to be the most common ( 50.0% ) in the mandible . in their study ,\nin which they used a different classification system , celikoglu et al . reported that in a turkish population vertical impaction was the most common in the maxilla ( 58.9% ) . in our research ,\nstudy result , and they used the same criteria in their study ( level b , 80% ) .\nhowever , they included all third molars , impacted or otherwise , in their study .\nthus , our result is not directly comparable to that reported by hugoson and kugelberg , or other study results . in this study , we only evaluated impacted third molars , and our reference was the amount of crown buried in bone .\nthe frequency of level a impaction was reported as only 5% by quek et al . in our research\nhowever , level a was observed in only 1 patient and thus was not analysed statistically .\nthere was significantly more level c impaction in the maxilla ( 46% ) than in the mandible ( 32% ) ( p = 0.02 ) and this result is comparable with that of quek et al .\ndachi and howel have indicated that the prevalence of unilateral and bilateral impaction of third molars was almost the same .\nhave reported that bilateral occurrence of third molar impaction was more common than unilateral impactions .\nour study also showed that bilateral impaction of itms was more frequent . in this study\nhowever , quek et al . indicated that the majority of bilateral third molar impactions were in the mandible .\nthey also reported that half of the bilateral impactions presented with the same classification of angle and level of impaction in the mandible , while this percentage was 71% in our research .\nour study showed that third molar impaction was present in 54.1% of a group of turkish orthodontic patients aged between 20 and 39 years , with no significant gender differences , and this frequency is the highest , thus far , to be reported in a turkish population .\nmesioangular and distoangular inclinations were the most common in the mandible and the maxilla , respectively . of all itms ,", "answer": "objective : we aimed to investigate the prevalence , distribution , angular position , and depth of third molar impaction in a turkish orthodontic patient population.materials and methods : we retrospectively reviewed the panoramic radiographs , intraoral photographs , and dental casts of 207 patients ( 62 men and 145 women ; age 20 - 39 years ) who had undergone orthodontic treatment at a university department of orthodontics for impacted third molars ( itms ) . \n a comprehensive chart review of all subjects was conducted . \n patient and treatment - related data were recorded in a digital database for comparative analysis.results:the prevalence of itms was 54.1% , and no statistically significant gender differences were evident ( 61.3% in men and 51.0% in women ; p = 0.23 ) . \n the frequency of maxillary itms was 49.3% ( 148 of 300 teeth ) while that of mandibular itms was 50.7% ( 152 of 300 teeth ) . the most frequently observed angulations of impaction were mesioangular for the mandible ( 65.1% ) , and distoangular for the maxilla ( 64.2% ) . \n of all the itms analysed , 61% were partially buried in bone and 39% were completely buried.conclusions:third molar impaction was evident in 54.1% of a group of turkish orthodontic patients aged 20 - 39 years , and there was no statistically significant gender bias . \n mesioangular and distoangular inclinations were the most common in the mandible and the maxilla , respectively .", "id": 478} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwithout appropriate management , herpes simplex encephalitis ( hse ) is a potentially fatal disease ( 1 ) . the mortality and morbidity rates remain high , even when an early diagnosis is made based on the detection of the herpes simplex virus ( hsv ) in the cerebrospinal fluid ( csf ) by a polymerase chain reaction ( pcr ) , and despite the advent of acyclovir therapy ( 2 ) . in particular , the acute - phase mortality and long - term outcome in patients with severe hse remain major concerns ( 3 ) .\nalthough the severity and poor outcomes of hse are mostly associated with acute - phase complications ( 2,3 ) , these important adverse events are not well understood because of the low frequency of the condition and the paucity of reported cases .\nthis lack of understanding may contribute to a lack of awareness by clinicians and , consequently , to the poor outcomes of patients with hse .\nwe herein report the case of a patient with hse that was complicated by cerebral hemorrhage ( the diagnosis of which was delayed ) , which developed at the end of 2 weeks of acyclovir therapy .\na 71-year - old woman was admitted to our hospital in a state of unconsciousness following fever and headache .\nshe experienced epigastric discomfort and dizziness 8 days before admission and gradually lost her appetite .\ntwo days later , she developed a fever of 38.2c , headache , and nausea .\nshe was evaluated twice by the outpatient service of our hospital for fever and was prescribed acetaminophen both times . however , in addition to the persistence of fever and headache , there was an acute worsening of her state of consciousness on the day of admission , and she was transported to our emergency department by ambulance .\nthe patient was placed under observation for 4 years at another hospital due to the presence of an unruptured aneurysm of the right middle cerebral artery .\nthe patient was a non - smoker and did not regularly consume alcohol . on physical examination ,\nher glasgow coma scale ( gcs ) score was e1v1m4 , her body temperature was 38.8c , her blood pressure was 116/66 mmhg , her pulse rate was 80/min , and her respiratory rate was 16/min with an o2 saturation of 99% ( with a flow rate of 3 l / min ) .\nher pupils were round and equally dilated ( size , 3 mm ) . a head and neck examination revealed no anemia , icterus , or other abnormalities .\nthe results of a cardiovascular examination were normal , and auscultation revealed normal lung sounds .\na neurological examination revealed no neck stiffness and normal deep tendon reflexes ; however , slightly rigid muscle tone and bilateral pathological babinski reflexes were observed .\nlaboratory investigations revealed a normal white blood cell count ( 7,350/l ) , a slightly elevated c - reactive protein ( 0.36 mg / dl ) level , elevated lactate dehydrogenase ( 313\niu / l ) levels , hyponatremia ( 128 meq / l ) , hypokalemia ( 2.9 meq / l ) , hypochloremia ( 88 meq / l ) , and a normal blood glucose level ( 126 mg / dl ) .\na urinalysis revealed no abnormal findings . a chest x - ray and electrocardiogram revealed no abnormalities .\nthe right anterior medial temporal lobe and insular cortex displayed high signal intensity on t2-weighted and diffusion - weighted brain magnetic resonance imaging ( fig .\n1a - c ) , and the patient 's aneurysm , which was already known to exist , was observed at the bifurcation of the distal m1 segment of the middle cerebral artery using magnetic resonance angiography ( fig .\n1d ) . a csf analysis detected moderate lymphocytic leukocytosis ( 170/l ) , a moderately increased protein level ( 77 mg / dl ) , and a slightly decreased glucose level ( 53 mg / dl ) .\ngram staining of the patient 's csf was negative , and blood and csf cultures showed no bacterial growth . a pcr of the csf to detect hsv-1 and hsv-2 revealed the presence of hsv-1 dna .\naxial t2-weighted images ( a , b ) and an axial diffusion - weighted image ( c ) show an area of high signal intensity in the right anterior medial temporal lobe and insular cortex .\nmagnetic resonance angiography ( d ) shows an aneurysm at the bifurcation of the distal m1 segment of the right cerebral artery .\nthe patient was treated with acyclovir ( 10 mg / kg , intravenously , three times per day [ ideal body weight ] ) , glycerol ( 200 ml , intravenously , twice a day ) , and additional supportive therapies .\nalthough the patient vomited on the day of admission , her symptoms disappeared within the first 2 days .\nher consciousness gradually recovered to gcs e4v4m6 , and her temperature returned to 37.3c on day 11 after admission .\nhowever , she vomited during the night on day 12 , and her gcs slightly worsened to e3v4m6 , and she displayed a slightly elevated body temperature of 37.6c on day 13 .\nan exacerbation of hse was considered , and a csf analysis including a pcr for hsv-1 was performed , which revealed mild bloody fluid with moderate lymphocytic leukocytosis ( 178/l ) and a markedly increased protein level ( 350 mg / dl ) .\nbrain computed tomography imaging performed on day 14 revealed cerebral hemorrhage in the right medial temporal lobe and right basal frontal area , with a right lateral ventricular rupture ( fig .\nalthough magnetic resonance angiography revealed an increase in the size of right cerebral arterial aneurysm ( fig .\n2d ) , no evidence of subarachnoid hemorrhage was observed by computed tomography or magnetic resonance imaging .\nacyclovir therapy was terminated based on the results of the second pcr for hsv , which was negative .\nthere was no recurrence of encephalitis or intracranial hemorrhage . computed tomography and magnetic resonance imaging at the time of cerebral hemorrhage .\naxial computed tomography shows acute cerebral hemorrhage in the right medial temporal lobe ( a ) and the right basal frontal area ( b ) . a right lateral ventricular rupture\nmagnetic resonance angiography ( d ) shows an increase in the size of the right cerebral arterial aneurysm at the bifurcation of the distal m1 segment of the right cerebral artery .\nwe herein report a case of cerebral hemorrhage that developed in a patient who was undergoing acyclovir treatment for hse . although the patient made a near - complete recovery , the diagnosis of the cerebral hemorrhage was delayed .\ninitially , an acute exacerbation of hse was considered , as intracranial vascular disease was not included in the differential diagnosis .\nthis case suggests that acute - phase complications of hse need to be better understood to avoid missing the onset of adverse events that can be managed successfully if they are diagnosed early .\nthe patient 's cerebral hemorrhage appears to have been associated with hse due to the following reasons .\nfirst , the site of hemorrhage was consistent with the region in which hse - associated inflammation was observed .\nsecond , the timing of the onset of hemorrhage was typical for hse - related cerebral hemorrhage ( 4 ) . although the precise cause of cerebral hemorrhage in hse patients remains unclear , based on the pathological findings in similar cases , we hypothesize that the rupture of the small vasculitic vessels of the brain due to hsv - induced inflammation was a possible mechanism of our patient 's bleeding ( 5,6 ) .\nin addition to cerebral hemorrhage ( 4 ) , seizures ( 2,3 ) , increased intracranial pressure ( 3,7 - 10 ) , stroke ( 11,12 ) , subarachnoid hemorrhage ( 13 ) , and central diabetes insipidus ( 14 ) have been reported as complications during the acute phase of hse ( this includes the period of acyclovir therapy ) .\nalthough the prevalence of these complications is not well known , seizures and increased intracranial pressure , which have been reported in one in three and one in five hse cases , appear to be among the most common ( 2,3 ) .\ncerebral hemorrhage and increased intracranial pressure have mostly been observed during acyclovir therapy , within 2 weeks after admission ( 3,4,7 - 10 ) ; the condition of patients may decline in this period due to hse and not because of complications , which can pose a challenge for the differential diagnosis .\nfurthermore , the symptoms of these two complications , which include deteriorated consciousness , headache , hemiparesis , hemiplegia , and third nerve palsy , are similar to those of hse ( 3,4,7 - 10 ) .\nthus , the possibility of a diagnostic delay may be higher in patients with cerebral hemorrhage and increased intracranial hypertension than in those with other complications .\nhowever , these two complications frequently require surgical intervention ( 3,4,7 - 10 ) . because both complications can be detected by computed tomography ( as in our case )\n, clinicians should consider repeat computed tomography to allow for the early detection of these potential complications in patients who display a worsening clinical condition despite the administration of acyclovir treatment .\nacute - phase complications in patients with herpes encephalitis . * in intensive care unit patients in conclusion\n, the diagnosis of cerebral hemorrhage during the early phase of hse may be delayed because of the similarity of its symptoms to the primary disease and due to the worsening of encephalitis .\nclinicians should consider cerebral hemorrhage and other acute - phase complications and re - perform imaging studies in hse patients who do not show any improvement during acyclovir treatment .", "answer": "herpes simplex encephalitis ( hse ) can be complicated by adverse events in the acute phase . \n we herein present the case of a 71-year - old woman with hse complicated by cerebral hemorrhage . \n she presented with acute deterioration of consciousness and fever and was diagnosed with hse based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction . the cerebral hemorrhage developed during acyclovir therapy ; however , its diagnosis was delayed for 2 days . after the conservative treatment of the cerebral hemorrhage , the patient made a near - complete recovery . \n cerebral hemorrhage should be considered as an acute - phase complication of hse .", "id": 479} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmales and females of c57bl/6-tg(ubc - gfp)30scha / j , c57bl/6j , b6.129p2(c)mecp2/j , b6.129p2-lyz2/j ( lysm ) , b6.129p2-mecp2/j , mecp2 , and c57bl/6j mice were purchased from jackson laboratories ( bar harbor , me ) ; b6.cg-mecp2 mice were a generous gift from dr .\nandrew pieper , ( southwestern medical school , dallas , tx ) and were maintained in our lab on c57bl/6j background .\nall procedures complied with regulations of the institutional animal care and use committee ( acuc ) at the university of virginia .\nfour week - old mice were subjected to lethal split - dose -irradiation ( 300 rad followed 48 hours later by 950 rad ) .\nfour hours after the second irradiation , mice were injected with 510 bone marrow cells .\nafter irradiation , mice were kept on drinking water fortified with sulfamethoxazole for two weeks in order to limit infection by opportunistic pathogens .\nfull methods and any associated references are available in the online version of the paper at www.nature.com/nature .\nmales and females of c57bl/6-tg(ubc - gfp)30scha / j , c57bl/6j , b6.129p2(c)mecp2/j , b6.129p2-lyz2/j ( lysm ) , b6.129p2-mecp2/j , mecp2 , and c57bl/6j mice were purchased from jackson laboratories ( bar harbor , me ) ; b6.cg-mecp2 mice were a generous gift from dr .\nandrew pieper , ( southwestern medical school , dallas , tx ) and were maintained in our lab on c57bl/6j background .\nall procedures complied with regulations of the institutional animal care and use committee ( acuc ) at the university of virginia .\nfour week - old mice were subjected to lethal split - dose -irradiation ( 300 rad followed 48 hours later by 950 rad ) .\nfour hours after the second irradiation , mice were injected with 510 bone marrow cells .\nafter irradiation , mice were kept on drinking water fortified with sulfamethoxazole for two weeks in order to limit infection by opportunistic pathogens .\nfull methods and any associated references are available in the online version of the paper at www.nature.com/nature .", "answer": "rett syndrome is an x - linked autism spectrum disorder . \n the disease is characterized in the majority of cases by mutation of the mecp2 gene , which encodes a methyl - cpg - binding protein 15 . \n although mecp2 is expressed in many tissues , the disease is generally attributed to a primary neuronal dysfunction 6 . however , as shown recently , glia , specifically astrocytes , also contribute to rett pathophysiology . \n here we examined the role of another form of glia , microglia , in a murine model of rett syndrome . \n transplantation of wild type bone marrow into irradiation - conditioned mecp2-null hosts resulted in engraftment of brain parenchyma by bone marrow - derived myeloid cells of microglial phenotype , and arrest of disease development . \n however , when cranial irradiation was blocked by lead shield , and microglial engraftment was prevented , disease was not arrested . \n similarly , targeted expression of mecp2 in myeloid cells , driven by lysmcre on an mecp2-null background , dramatically attenuated disease symptoms . thus , via multiple approaches , wild type mecp2-expressing microglia within the context of an mecp2-null male mouse arrested numerous facets of disease pathology ; lifespan was increased ; breathing patterns were normalized ; apneas were reduced ; body weight was increased to near wild type , and locomotor activity was improved . \n mecp2+/ females also exhibited significant improvements as a result of wild type microglial engraftment . \n these benefits mediated by wild type microglia , however , were diminished when phagocytic activity was inhibited pharmacologically using annexin v to block phosphatydilserine residues on apoptotic targets , thus preventing recognition and engulfment by tissue - resident phagocytes . \n these results suggest the importance of microglial phagocytic activity in rett syndrome . \n our data implicate microglia as major players in rett pathophysiology , and suggest that bone marrow transplantation might offer a feasible therapeutic approach for this devastating disorder .", "id": 480} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nreverse shoulder prosthesis is an excellent surgical option for patients with certain shoulder pathologies , of which rotator cuff arthropathy is one .\none area where we are gaining a greater understanding is that of managing acromial pathology .\nrecent studies are showing that not all acromial pathology is a contraindication to reverse shoulder arthroplasty ; in both pre- and post - operative patients , small lateral fractures of the acromion can be treated non - operatively or fixed surgically with a tension band technique .\noverall , results comparable to that of reverse arthroplasty can be achieved with either of these treatment options .\nhowever , fractures at the base of the acromion or of the scapular spine present a different problem . in these types of fractures , a larger length of deltoid muscle is detached , and therefore defunctioned . in reverse shoulder arthroplasty , in order to achieve a stable shoulder , the deltoid must be tensioned a great deal .\nthis in turn causes a deforming force and distraction at the fracture site , making for a poor healing potential . also , as the reverse shoulder prosthesis relies on the deltoid muscle to move the arm , if the deltoid is detensioned or improperly tensioned , this will lead to poor functional capacity .\nwe present a case of treatment of a fracture at the base of the acromion using a 90/90 plating construct that healed in a good position .\na 71-year - old right - handed woman presented with a 2-year history of right shoulder pain and dysfunction , which began abruptly when lifting a heavy load . at the initial evaluation ,\nher range of motion was limited , particularly in active abduction as she achieved only 45 degrees in this plane . a cuff arthropathy ( hamada grade 3 )\nwas diagnosed and the decision was taken to proceed with reverse shoulder arthroplasty . to complete the pre - operative assessment ,\na ct scan was performed which confirmed there was no acromial pathology involved . a reverse shoulder prosthesis and a biceps tenodesis\nwas carried out ( delta xtend , depuy , warsaw , in , usa ) through a deltopecoral approach [ figure 1 ] .\nthe patient 's right arm was immobilized in a sling and the range of motion exercises were started 6 weeks after arthroplasty [ figure 1a ] .\nfive months after surgery , she sustained a blow to the right shoulder but sought medical attention 1 month later , at her scheduled follow - up visit .\nradiographs showed a displaced fracture at the base of the acromion [ figure 1 ] .\nthis showed that both the humeral and glenoid components were well fixed and the only pathology was the fracture .\nantero - posterior radiographs showing the patient 's right shoulder immediately after reverse shoulder arthroplasty ( a ) and after fracture , 5 months later ( b ) .\nthe post - operative image shows no pre - existing acromial pathology she was taken to the operating room and her previous incision was extended into a sabre incision to better expose the acromion .\ntwo small fragment ( 3.5 mm ) locking plates ( synthes , west chester , pa , usa ) were used in a 90/90 configuration ; one was a fragment specific clavicular plate and the other a reconstruction plate .\nthe fragment specific clavicular plate was applied on the superior edge of the scapular spine in a compression mode .\na second reconsrtuction plate was applied from the posterior acromion to the posterior cortex of the scapular spine , in the infraspinatus fossa .\nfixation was solid , but in order to protect the construct , the patient was placed in an abduction brace for 6 weeks .\neighteen months after fracture fixation , the patient was satisfied with the clinical result [ figure 2 ] .\nshe was capable of 125 degrees of abduction , 160 degrees of forward flexion , 85 degrees of external rotation in adduction , and 60 degrees of internal rotation .\nher quickdash score was 29.5 ( compared to 82.5 pre - op ) and constant score was 69 on the affected side compared to 85 on the left side , for a good functional outcome .\na medline search using the key words [ acromion fracture ] , [ scapula fracture ] , [ reverse arthroplasty ] was performed .\nwe then sought to classify and separate the cases by location ; there were 30 cases of fractures at the base of the acromion , and scapular spine . when our case is added , we have a total of 31 cases .\nresults are summarized in table 1 . in brief , of the 30 more proximal cases , 21 were treated non - operatively in a sling , 7 were treated with open reduction and open fixation and one with revision of the prosthesis . of those treated non - operatively , and for whom results are published , fourteen had a non - union , four had a malunion and in two cases , it was unclear whether union was achieved . for patients receiving fixation of the fracture , there was one non - union , two repeat fixations , and one patient required removal of the fixation .\nthe patient who had a revision of the prosthesis had a malunion of the acromion .\nresults of the literature review . in the fracture location column , the fracture description provided by the authors is presented .\nalthough recent studies have shown that good outcomes may be achieved with non - surgical management of lateral acromial fractures , the same does not hold true for basal acromial fractures .\nthe likely reason for this is that with fractures at the base of the acromion , a large length of the deltoid is defunctioned and the deltoid muscle is essential to the functioning of the reverse shoulder prosthesis .\npreviously described techniques , such as tension band fixation achieved poor functional results for fractures at the base of the acromion .\nwe postulate that this is because the fixation method is insufficient to withstand the forces generated by the deltoid muscle a tension band can neutralize forces parallel to the axis of the band but in the case of the deltoid , force vectors are generated in different directions .\nit also allows for compression along the fracture site and resists motion in all directions .\ngood screw purchase can be achieved by angling the screws either toward the scapular spine or the coracoid .\nthe locking option enables good fixation and improves cut - out strength in osteopenic or osteoporotic bone .\nin addition to the stable fixation achieved with this technique , we further recommend immobilization of the affected shoulder using a sling and an abduction pillow to detension the deltoid , thus at least partially removing the distractive forces at the fracture site . also essential to achieving a good functional result\nwe thus also recommend a program of range of motion exercises followed by strengthening exercises to maximize functional capabilities . based on results from previous studies ,\nfractures of the tip were those of the most lateral or anterior portion of the acromion .\nfractures of the body of the acromion are those medial to the tip of the acromion and lateral to the beginning of the scapular base .\nthe scapular base is the lateral border of the scapular spine , which is smooth and round . in our nomenclature ,\nfractures at the scapular base are termed fractures at the base of the acromion as functionally , this zone connects the acromion to the rest of the scapula and this term avoids confusion with any more medially occurring fractures .\ncoronal ( a ) and axial ( b ) representations of the proposed classification scheme for acromial fractures associated with revere arthroplasty we propose the above mentioned classification system as it provides a nomenclature for acromial fractures that is descriptive and is based on the anatomy and functionality of the scapula . as the results from the review of the literature indicate , the more medial the fracture , the worse the prognosis with non - operative treatment .\nthus , this classification system may be used to predict outcomes and determine treatment offered .\nit differs from other classification systems ( crosby ) in that it further subclassifies more medial fractures , which are the more ominous fractures . as more research is carried out in this field", "answer": "fractures of the acromion and scapula are known to occur after reverse shoulder arthroplasty . \n we present a case of a fracture at the base of the acromion 5 months after arthroplasty treated successfully with dual plating of the acromion . \n eighteen months after fracture fixation , the patient had 160 degrees of active forward flexion , a quickdash of 29.5 , a constant score of 69 and she was satisfied with the result . a concomitant review of the literature produced , in addition to our patient , 56 cases . \n these were used to produce a classification system , based on bony and functional anatomy as follows . \n tip fractures are of the most lateral or anterior portion of the acromion , those of the body of the acromion are medial to the tip but lateral to the beginning of the scapular base \n . fractures at the scapular base are termed fractures of the base of the acromion and those more medial to that , fractures of the scapular spine . \n the functional results of these case series demonstrated poorer functional outcomes for more medial fractures . \n as future research in this domain increases , clarity on the nomenclature of these fractures will allow for prognostication and treatment based on fracture location as well as comparison between studies .", "id": 481} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 19-year - old patient was admitted for low back pain and radiating pain in the posterior aspect of the left leg which had begun 2 months prior .\nshe was treated with nonsteroidal anti - inflammatory drugs , physical therapy , and an epidural block in the local hospital .\nshe mainly complained of pain in the left leg , with a score of 6/10 on the visual analogue scale ( vas ) , and a result of 50 degrees in a passive straight leg - raising test .\nthere were no sensory - motor abnormalities , and the tests for reflexes showed normal responses .\nmagnetic resonance imaging ( mri ) revealed central herniation of the l4-l5 intervertebral disc , which compressed the dural sac ( fig .\ndiscectomy was suggested , as the patient complained of consistent and severe pain , the mri findings showed severe spinal stenosis , and there were no responses to conservative treatment .\ntherefore , we decided to treat her with percutaneous epidural neuroplasty with a racz catheter on the left l5 spinal nerve root . after obtaining her informed consent ,\nprophylactic antibiotics ( ceftezole 1 g ) were administered intravenously after negative skin test confirmation .\nroutine monitoring equipment - including an electrocardiogram , blood pressure monitor , and pulse oximeter - were applied , and she was placed in the prone position on the fluoroscopy table .\na pillow was inserted under the abdomen to correct the anteflexion of the lumbar vertebrae , the legs were abducted , and the feet were inverted . following sterile preparation and draping , the location of the sacral hiatus was confirmed by fluoroscopy , and a local infiltration of 1% lidocaine was performed in the insertion area ( 1 inch right lateral and 2 inches caudal from the sacral hiatus ) .\nthe tip of the needle was placed between the s3 and s4 vertebrae , whose locations were confirmed by fluoroscopy with a c - arm . after confirming negative aspiration of the blood or cerebrospinal fluid ( csf ) , 10 ml of water - soluble contrast media were injected for the epidurogram .\nthe racz catheter was inserted through the needle and was advanced towards the left l5 nerve root under continuous fluoroscopy ( fig .\n2 ) . 1,500 units of hyaluronidase in 10 ml of normal saline were then injected . additional dye ( 2 ml ) was injected to confirm the contours of the nerve root , and 9 ml of 0.2% ropivacaine and 1 ml of 4 mg dexamethasone were injected following negative aspiration .\nthe patient did not complain of severe pain , paresthesia , or unusual responses during the procedure .\nafter 1 hour , the patient complained of sudden motor weakness in the right lower limb , on the site opposite to where the neuroplasty was conducted .\nthe great toe dorsiflexion was marked as motor grade i , and the ankle dorsiflexion as motor grade ii .\nparesthesia and a dull sensation in the right l4-l5 dermatome had developed , but the patient did not complain of pain . at first\n, we suspected a temporary motor weakness caused by ropivacaine , and the symptoms were observed for one hour .\nan urgent mri was performed , but no epidural hematoma or suspicious lesions were found ( fig .\naround 4 hours after the neuroplasty , the motor and sensory weakness had not improved ; emergency surgery was therefore performed .\ndiscectomy of the l4-l5 intervertebral disc was conducted . during the surgery , central and left paracentral protrusions of the disc\nwere found , and swelling of the right l5 nerve root was also discovered . after the surgery\nthe motor strength and sensory function of the right leg had returned to normal . in the 10-day follow - up period\n, there were no signs of motor or sensory abnormalities , and the patient was therefore discharged without any discomfort .\nbleeding , infections , or nerve damage can generally develop after epidural neuroplasty , but motor and sensory weaknesses are rare complications\n. acute monoplegia following epidural adhesiolysis has previously been reported in a patient with failed - back syndrome and foraminal stenosis of the l4-l5 levels . however , to the best of our knowledge , there has been no report of acute motor weakness in the opposite lower extremity after percutaneous epidural neuroplasty .\nfirst , motor weakness can be caused by direct nerve injury from the epidural needle or racz catheter during the procedure .\nhowever , this was unlikely in this case , as there were no complaints of acute severe pain , sensory abnormality , or abnormal responses during the procedure .\nthis was also unlikely in this case , as these injections cause bilateral or patchy blocks of the motor and sensory functions .\nfourth , although nerve damage from hypertonics can be a reason , we did not use hypertonic saline .\nfinally , injection of a large volume of fluid into the epidural space may cause a transient neurological deficit .\nrocco et al . reported that epidural injections after spinal surgery may cause complications such as cauda equine syndrome or nerve root damage as the epidural space after surgery is limited , and the injected drugs may increase the pressure and cause nerve damage either directly or by ischemia , due to decreased blood flow .\nthey presented acute right monoplegia which had occurred after epidural adhesiolysis of the bilateral l5 nerve root in a patient with failed - back surgery syndrome , with spontaneous recovery after 5 weeks .\nthey suggested that the large volume of fluid injection might have been the reason for the transient neurological deficit , as a compartment loculated by the fluids might have compressed the nerve .\nthey also suggested careful injection under observation of the excretion of the contrast dye through the neural foramen in order to prevent nerve injuries caused by compression from a large volume of injected drugs .\nin particular , if the spinal stenosis is severe , the epidural injection may increase the pressure in the epidural space , and even a mild edema around the nerve root may cause a neurologic deficit by compression of the nerve root .\nwe hypothesized that the large volume of fluid injected during the epidural neuroplasty and the severe spinal stenosis might have been the reason for the opposite motor weakness in this case , as per the previous reported case .\nthe patient in the present study presented severe spinal stenosis , with a herniated disc occupying more than 2/3 of the spinal canal .\nthe epidurogram during the neuroplasty showed a better spread of the contrast dye in the left side , and a filling defect on the right side .\nmoreover , the central protrusion may have increased the pressure on the right side of the epidural space , and the closed compartment may have caused loculation , leading to barotrauma in the right l5 nerve root .\nin addition , swelling of the l5 nerve root was observed during the surgery , and the motor and sensory functions returned to normal immediately after the surgery , suggesting that the latter had a decompressive effect .\nhowever , further evaluations , including measurement of the pressure and radiologic tests , are required to prove this theory . in conclusion\n, we presented a rare case of unilateral motor weakness following epidural neuroplasty , on the side opposite to the lesions .\nthe injection of a large amount of fluid during neuroplasty in a patient with spinal stenosis may cause compressive nerve damage .", "answer": "recently , percutaneous epidural neuroplasty has become widely used to treat radicular pain caused by spinal stenosis or a herniated intervertebral disc . \n a 19-year - old female patient suffering from left radicular pain caused by an l4-l5 intervertebral disc herniation underwent percutaneous epidural neuroplasty of the left l5 nerve root using a racz catheter . \n after the procedure , the patient complained of acute motor weakness in the right lower leg , on the opposite site to where the neuroplasty was conducted . \n emergency surgery was performed , and swelling of the right l5 nerve root was discovered . \n the patient recovered her motor and sensory functions immediately after the surgery . \n theoretically , the injection of a large volume of fluid in a patient with severe spinal stenosis during epidural neuroplasty can increase the pressure on the opposite side of the epidural space , which may cause injury of the opposite nerve by barotrauma from a closed compartment . \n practitioners should be aware of this potential complication .", "id": 482} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prostate is the site of two common diseases in aging men , benign prostatic hyperplasia and prostate cancer ( pca ) .\nepidemiological studies show that , in the united states , pca accounts for 28.7% of new non - skin cancers and 12.7% of cancer - related deaths.1 androgen deprivation therapy ( adt ) retards pca progression in 60%80% of patients but may cause cardiovascular complications and alterations in body composition , lipoprotein metabolism , and sexual function . in general , adt may result in a decreased quality of life .\nfurthermore , studies in men demonstrate that low serum testosterone ( t ) levels are associated with several cardiovascular risk factors,2,3 such as lower high density lipoprotein cholesterol , higher triglyceride concentrations , hyperinsulinemia , and increased abdominal adiposity .\nthese factors are all characteristic of the metabolic insulin resistance syndrome . in addition , many patients treated with adt experience rapid bone loss that increases the risk of debilitating osteoporotic fractures.46 reports indicate that total and free levels of serum t decline in aging men and that abdominal visceral fat is inversely associated with t levels . resting energy expenditure ( ree ) , which accounts for 60%70% of total daily energy expenditure ,\ndecreases with age , physical inactivity , sympathetic nervous system and endocrine status.7,8 to our knowledge , the effects of adt on ree have not been fully explored in controlled trials .\nthe goal of this prospective study was to determine the effects of adt on body composition and resting metabolic rate in patients with metastatic pca .\nsixteen men , aged 63 to 96 years ( mean age 71 ) , with untreated metastatic pca were enrolled in this study . prior to orchiectomy , all patients were evaluated clinically and by laboratory analysis to establish a baseline . after a careful medical history had been taken from each patient , we assessed several exclusion criteria , namely , cognitive alterations , depression and emotional liability .\nlaboratory examinations included tests of fsh - lh serum concentrations , and an evaluation of body mass index , fat / lean body mass , bone mineral density , carbohydrate / lipid oxidation , and resting energy expenditure .\nfollowing orchiectomy , the same evaluation was carried out monthly and after 12 months , the period chosen for final analysis . to evaluate body composition\n, all patients underwent densitometry testing ( dual - energy x ray absorptiometry - dexa).9 the ree , fat and carbohydrate oxidation levels were measured using indirect calorimetry , with a delta - trac metabolic monitor.10 body composition analyses and indirect calorimetry were carried out at baseline and after 12 months following the orchiectomy procedure . written consent was obtained from all patients , and this protocol was approved by the ethics committee at our institution .\nwe used the non - parametric two - sided wilcoxon t - test , and p<0.05 was considered significant to appropriately compare time differences for each variable.11\nwe used the non - parametric two - sided wilcoxon t - test , and p<0.05 was considered significant to appropriately compare time differences for each variable.11\nstatistically significant differences in body composition pre and post orchiectomy were seen in terms of weight , body mass index ( bmi ) and lean body mass ( lbm ) .\ntotal fat body mass ( fbm ) exhibited a tendency to increase but failed to reach significance .\nno significant changes were observed in bone mineral density ( bmd ) and ree , but we identified a statistically significant change in terms of increased carbohydrate oxidation ( choox ) and a decrease in lipid oxidation ( lipidox ) .\naging is associated with sarcopenia ( loss of muscle mass ) , with an average 12 kg loss of lbm between the ages of 25 and 70 years and an increase in fbm of 18%36% during the same period.2 testosterone levels exhibit a positive correlation with lbm and a negative correlation with fbm .\nthis has led to the hypothesis that adt may help mitigate age - related alterations in body composition .\nour study reports two major findings : 1 ) adt was associated with decreased body weight and with decreased lbm ; 2 ) adt led to increased choox and decreased lipidox .\nandrogens modulate body composition , including lipid and protein metabolism.12 smith et al,13 galvo et al,14 levy et al,15 and van londen et al16 observed significant changes in metabolic and body composition parameters after 6 months of induced hypogonadism in all patients .\nthe researchers observed a significant increase in fbm ( 20.29.4 to 21.99.6 kg,13 13.82.3%,14 1.172.3 % , 15 and 2167.15 g,16 respectively ) and a significant decrease in lbm ( 63.28.0 to 62.35.4 kg,13 2.4 0.4%,14 1.152.20%;15 and 1785.81 g,16 respectively ) with no significant changes in total body weight , lipid readings or glucose metabolism .\nthey also reported a positive correlation between the changes in fbm and insulin concentrations ( r=0.56 ; p=0.013 ) .\nthese results are in agreement with other studies that demonstrated a relationship between t and abnormalities in carbohydrate and lipid metabolism.17 in healthy male populations , low t concentrations are negatively correlated with the degree of central abdominal obesity . in hypogonadal males , there is a tendency toward increased visceral adiposity and reduced muscle mass that can be reversed by androgen replacement.18 the underlying mechanisms for these observations are not well defined , but androgen receptors are known to be present on visceral adipocytes .\nit is likely that t is directly involved in the mobilization of free fatty acids.19 we observed significant changes in metabolic and body composition in our patients after adt .\nwe identified significant decreases in total body weight , bmi and lbm ( 2.5 kg , p = 0.01 ; 0.8 kg / cm , p = 0.02 , 11.7 kg , p = 0.002 , respectively ) .\nfbm was found to increase ( 7.15 kg , p = 0.06 ) with no significant change in bone mineral density ( bmg ) .\nthere were no changes in ree , but we did identify a significant increase in choox and a decrease in lipidox ( 52.62% , 4.10% respectively ) . in one study , suppression of t levels after 10 weeks of gnrh agonist administration was found to reduce ree in young men .\nin this study , researchers were unable to determine whether the effect was directly mediated by a reduction in t levels or if it was due to a subsequent reduction in t aromatization to estrogen.20 we were unable to show alterations in ree in our study , possibly due to the size of our study sample .\nthe altered concentrations of gonadotropins following orchiectomy may be linked with the effects of this procedure on the pituitary gland .\nit is important to consider that adt not only acts on pca but also affects metabolism , including hematogenesis , bone , fat , protein , and sarcho - metabolism . despite pca being one of the leading causes of death , a substantial proportion of aging patients die of unrelated causes that are due to comorbidities , often in the context of metabolic syndrome .\nto our knowledge , this is the first prospective study to examine changes in body composition , resting energy expenditure , and consequences involving the oxidation of carbohydrates and lipids in the context of adt .\na study on a larger group of patients would be of great interest once a limited number of patients included from only one centre may be considered a limitation in this study .\nafter 12 months of androgen deprivation therapy , elderly males with metastatic prostate cancer exhibit declines in lean body mass and lipid oxidation , together with an increase in carbohydrate oxidation .", "answer": "introductiontestosterone is needed for normal male development , muscle strength , bone mineralization , hematopoietic function , and sexual and reproductive functions . \n the main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression , but therapy is often accompanied by significant adverse effects.objectivethis study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer.patients and methodsa prospective study was performed to evaluate the body composition of 16 elderly males ( aged 6396 ; median age 71 ) with prostate cancer scheduled for orchiectomy , one year before and after surgery . \n body composition was measured by dexa , and energy expenditure , fat and carbohydrate oxidation were measured by indirect calorimetry.resultsbody weight ( p=0.01 ) , lean mass ( p=0.004 ) , and lipid oxidation ( p=0.001 ) decreased significantly . \n carbohydrate oxidation ( p=0.02 ) , fsh ( p=0.0001 ) and lh ( p=0.0001 ) levels increased significantly . \n changes in fat mass ( p=0.06 ) and bone mineral density ( p=0.48 ) were not significant.conclusionsafter 12 months of androgen deprivation therapy , elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation , together with increased carbohydrate oxidation .", "id": 483} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\northodontic anchorage is a basic procedure necessary for a successful treatment . for \n this reason ,\nclinicians seek to better understand various orthodontic devices , such as \n headgear , transpalatal arch , lingual arch , and nance 's button .\nthese devices allow a \n certain degree of movement of the anchorage unit and are dependent , to varying degrees , \n on patient compliance . in severe cases or in cases of non - cooperative patients , \n treatment could be compromised .\nrecently , skeletal anchorage has increased in popularity \n due to the benefit of direct transfer of the point of anchorage from the teeth to the \n skeleton . however , since \n these mini - implants have been used in orthodontics , a small displacement during \n treatment has been detected .\nthe mini - implant displacement allows contact between the \n screw and the dental root , causing damage to the root or the periodontal ligament , \n potentially leading to mobility or loss of the mini - implant .\nunfortunately , there is not much information available on the displacement or adverse \n effects of mini - implants .\nrecently , hsieh , et al . ( 2008 ) found that even endosseous titanium implants may not \n necessarily serve as a rigid orthodontic anchorage at all force levels .\n( 2004 ) investigated cephalometric \n tracings and found a noteworthy extrusion and tipping forward of mini - implants after \n en - masse retraction of anterior teeth . recently\n, tomographic studies have evaluated the \n position of mini - implants in both jaws , though without relating them to longitudinal \n control . to the best of our knowledge ,\ngeneral dentistry and orthodontics constantly use radiographs with the main purpose of \n assessing the validity of treatment methods . zanda ( 2007 ) described a new film holder for occlusal film that showed \n effective reproducibility of occlusal radiographic images in dry skulls ( figure 1 ) , making it possible to take an occlusal \n radiographic sequence at different times .\n( 2005 ) used dry human skulls to analyze the reliability \n in determining tooth position in posterior - anterior films .\nusing markers inserted in the \n bands of molars and premolars from hyrax expanders allow identifying each one in each \n side on posterior - anterior films .\nocclusal x - ray film holder and skull positioned for standardized occlusal \n radiograph the purpose of the present study was to evaluate the reliability and accuracy of a \n radiographic analysis method for identifying the location of mini - implants inserted in \n the posterior region of the maxilla in dry human skulls .\nthree human skulls were obtained from the anatomy department of the dental school of the \n university center of maranho , brazil .\nall skulls had preserved maxilla and mandible and \n sufficient teeth on the posterior area of the maxilla for the successful placement of \n mini - implants . the cortical bone condition and\nthe maxillary interadicular space were \n evaluated using radiographic images between the second premolars and the first molars . \n according to the same technical criteria used for patients ,\nsix self - drilling \n mini - implants ( 1.6x1x7 mm ; osas , dewimed , tuttlingen , germany ) were placed between the \n second premolars and the first molars at a 45 angle relative to the tooth 's long \n axis .\nonce the study began , the main purpose was to test the reliability of different \n operators for the proposed method in this research .\ntherefore , clinical operators with \n various levels of professional experience were invited to take the occlusal radiographs . \n\nthree operators were selected : an orthodontist , an implantodontist and an undergraduate \n dental student .\neach operator performed three occlusal radiographs taken at three \n intervals of 15 days in each of the three skulls .\nthe set of three radiographs of each \n skull was identified externally according to an identification number for the skull , the \n operator and the time .\na total of 27 randomized occlusal radiographs were obtained using insight io-41 film \n ( size 5.7 cm x 7.6 cm ; kodak ) with 1.5 s exposure time at 10 ma and 70 kv .\nthe occlusal \n radiographs were taken with a correct alignment between the cylinder localizer from the \n x - ray machine and the ring from the occlusal radiographic position self - drilling film . \n\neach operator took the occlusal radiograph for each of the skulls with the occlusal \n films inserted in the zanda ( 2007 ) \n film holder and fit the film in more number of posterior teeth of the maxilla .\nall radiographs and a ruler with same lateral size were digitized using a scanner \n ( be@rpaw 2400ta plus , scanner a4 ) ( figure 2 ) .\nthe \n radiographs were measured using macbiophotonics imagej software originally applied in \n biologic researches for microscopic image capture .\nafter the mini - implant positions , the points were defined and \n measured using a cartesian coordinate system ( figure \n 3 ) .\nthe cartesian system was composed by the following measures : occlusal radiographs with mini - implants placed occlusal radiographs and measurements line a : a straight line traced over the maximum number point of the midpalatal suture ; line b : a line perpendicular to the intersection of line a at the virtual point \n representative of the incisive foramen ; distance xd : for the mini - implant on the right side , the minimum distance from the head \n of the mini - implant to line a ; distance yd : for the mini - implant on the right side , the minimum distance from the head \n of the mini - implant to line b ; distance x ' d : for the mini - implant on the right side , the minimum distance from the tip \n of the mini - implant to line a ; distance y ' d : for the mini - implant on the right side , the minimum distance from the tip \n of the mini - implant to line b ; distance xe : for the mini - implant on the left side , the minimum distance from the head \n of the mini - implant to line a ; distance ye : for the mini - implant on the left side , the minimum distance from the head \n of the mini - implant to line b ; distance x ' e : for the mini - implant on the left side , the minimum distance from the tip \n of the mini - implant to line a ; distance y ' e : for the mini - implant on the left side , the minimum distance from the tip \n of the mini - implant to line b. the means and standard deviations of the distances on each side were calculated \n considering the operator and the skull ( table \n 1 ) .\nthe intra - operator reliability for the measurements was estimated using the \n interclass correlation coefficient ( icc ) .\nanalysis of variance ( anova ) was used to test \n the effect of different image times and different operators . mean and standard deviation ( sd ) for each measurement and operator ( op )\nstatistical analysis indicated a significantly high , positive correlation between the \n maxillary occlusal radiography taken by the different operators ( table 2 ) .\nintra - operator reliability for mini - implant measurements expressed as interclass \n correlation coefficient ( icc ) ( n=3 ) the icc test verified the measurements of each variable made by each operator on each \n skull that localize the head and the tip of the mini - implant ( x , y , x ' and y ' ) . \n\nintra - operator correlations were above 0.87 for all the operators and each of the skulls \n ( table 2 ) .\nthis value seems to indicate a \n similar variation , indicating an excellent reproducibility through a positive and high \n correlation . in terms of the effect of time\n, the operator and its interactions showed no \n statistically significant differences in any of the variables analyzed by anova ( table 3 ) .\nthe goal of the present study was to test the reliability and accuracy of the \n radiographic occlusal position developed by zanda ( 2007 ) used as a device to verify the stability of \n posteroanteriorly and lateromedially positioned orthodontic mini - implants .\nthe \n hypothesis was that this method can be used as a replicate for maxillary occlusal \n radiographs for location of mini - implant placement in the posterior region of the \n maxilla . since the introduction of the cephalostat as a standard for taking cephalometric \n radiographs ,\nthe cephalostat has been traditionally used to determine the direction and \n amount of skeletal and dental changes .\nseveral devices have also been developed and \n improved with longitudinal research in orthodontic patients .\nsome studies have reported \n that film holders and markers of anatomic structures contribute to the improvement in \n radiographic images . also creating more information about the position of structures \n during orthodontic treatments .\nbased on these presumptions , our study \n used a model of an occlusal x - ray film holder to obtain the most uniform radiographic \n series . additionally , the selected anatomic structures used as references to determinate \n the measurements were chosen because they are known to be stable during treatment .\nthis study showed that the use of the occlusal x - ray film holder is sufficiently \n accurate for investigations of mini - implant stability and an alternative to \n cephalometric analyses for determinate mini - implant displacement .\nfurthermore , the \n numerical information on the displacement of the mini - implants can be correlated with \n the amount of dental movement determined by the retraction .\n( 2004 ) reported that mini - implants do \n not remain stable at forces higher than 400 g. these findings suggest that studies are \n necessary to quantify mini - implant displacement caused by treatment , especially by means \n of the innumerable variables related to the use of this transitional anchorage \n device .\nour findings show that future clinical studies will be able to evaluate the direction of \n the displacement of the mini - implants .\nalso , different types of this skeletal anchorage \n device could be compared considering the thickness , the design and the length with the \n suffered displacement .\ncomputed tomography ( ct ) scans are not routinely used to improve the quality of \n craniofacial measurements in orthodontics .\nthe present data prove that the method \n presented here is valid and can be performed at a much lower cost compared to ct .\nthis \n means that clinicians and researchers can better understand this innovative modality of \n anchorage using an easily attainable and low - cost material .\nanother important benefit of \n this method is a lower exposure of patients to radiation to detect the stability of the \n mini - implants .\nwe believe that clinical studies on this topic are very important for \n further acknowledgment of transitory anchorage device .\nhowever , there is a great deal of \n responsibility in deciding to prescribe radiographs , especially ct scans ; it is \n complicated and depends on the effects on the orthodontic therapy management .\nhuman skulls were used for safety reasons due to the potential exposure of patients to \n ionizing radiation .\nthe adopted model simulates similar conditions used for patients , \n with a reduced x - ray exposure time . \n\nadditionally , the anatomic structures used to obtain all measurement tracings are easily \n identified , as well as their presence in the same plane and height as the indicated \n inserted mini - implant in the posterior maxillary area .\n, we believe that the selected areas are not influenced by \n soft tissue thickness and do not compromise the visualization of the anatomic structures \n used and the installed mini - implants . the number of dry skulls used in this type of study has revealed variations in other \n studies .\nthe number of \n skulls used in the present study was sufficient to verify the influence of individual \n anatomic variations in the statistical analysis .\nit should be noted that we opted for a \n research design that did not evaluate the anatomic aspects in relation to accuracy and \n reliability .\nthe aim of the \n study was to analyze operator 's reproducibility on separate occasions .\nthe intraclass \n correlation proved that , with the skull change and , consequently , the occurrence of \n anatomic variations , a high and significant correlation was found among the different \n measurements of each skull .\nthe agreement in the operators ' measurements ( table 3 ) shows that this method is useful for research and for \n clinical evaluation . for clinical use\n, it is indicated to attach the film to the film \n holder ( figure 1 ) and after adaption inside of the \n mouth , ask for the patient to occlude . only with the dental occlusion is possible to \n achieve stability to use this intraoral radiographic technique .\nzanda ( 2007 ) found variations in the \n reliability of measurements far from the occlusal plane , whereas the present study \n showed no statistically significant differences .\nin the present study , this \n reproducibility was found because the mini - implants and the anatomic structures used the \n same plane into the maxilla , both are at the same tall of palatal plane .\nvariables \n describing the position of the head and the tip of the mini - implant were in the same \n plane .\nalso , the midpalatal suture was chosen as a reliable reference for the \n determination of a measurement for each variable .\nit should be mentioned that the method \n presented here only identifies mini - implant localization on the posterior region of the \n maxilla .\nthis implies that , in future studies , an additional use for this method in \n another site of the maxilla or mandible may be the identification of a more reliable \n anatomic structure for each studied region .\nthe results of the present study demonstrate that this radiographic method was highly \n reproducible among operators and accurate for the identification of measurements . also , \n no differences were observed based on the time and the operator using this method .\nthese \n results support the use of this standardized method for occlusal radiographs for \n mini - implant identification on the posterior maxilla .", "answer": "objectivethe purpose of this study was to evaluate the reliability and accuracy of a \n radiographic analysis method for the location of mini - implants inserted in the \n posterior region of the maxilla . \n material and methodstwo self - drilling mini - implants were installed between the second premolar and the \n first molar on the right side and left side in three dry skulls . \n three operators \n performed three occlusal radiographs , using an occlusal x - ray film holder , at \n three different times in each of the three skulls . \n resultsthe interclass correlation coefficient showed a significantly high , positive \n correlation ( p<0.05 ) , indicating an excellent reliability between operators . \n \n the analysis of variance showed no significant differences in time and among the \n operators . \n conclusionbased of these findings , it may be concluded that this methodology can be used by \n several operators in longitudinal clinical studies on orthodontic mini - implants at \n the anterior - posterior and lateral - medial locations or longitudinal \n displacement .", "id": 484} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is an infection caused by various fungal species of trichophyton , epidermophyton , and microsporum genera , together known as dermatophytes belonging to order onygenales .\nterbinafine was added to this list of antifungals in the early 1990s and has since then shown good efficacy in widespread tinea infections .\nit is the only orally available allylamine antifungal . with a favorable mycological and pharmacokinetic profile ,\nterbinafine is considered to be a first - line drug for the treatment of tinea corporis and cruris .\nsqualene epoxidase is an enzyme responsible for synthesis of ergosterol , an important component of fungal cell membrane .\nthis ultimately results in fungal cell wall disintegration allowing terbinafine to exert its fungicidal action .\nthe side effects include gastrointestinal side effects such as nausea , vomiting , and abdominal pain .\nthe drug has shown consistent efficacy against dermatophytes achieving more than 90% cure rates at a dose of 250 mg / day when administered for 2 weeks . however , recently , we have observed decreased efficacy terbinafine in patients with tinea infections .\nthis study is aimed at documenting these cases of terbinafine therapy failure in patients of tinea corporis and/or tinea cruris .\nwe also tried to see the correlation of this resistance with the species involved as well as the percentage of body surface area involved .\nthe study was carried out in northern part of india during spring and summer season with an average humidity of 70% and an average temperature of 28c .\npatients diagnosed to have tinea corporis and/or tinea cruris on clinical examination and involving more than 1% body surface area were taken up for the study .\nthe diagnosis was made by clinical examination followed by 10% koh smear and culture in all the patients .\nonly culture positive patients were included in the study and culture negative patients were excluded from the study .\npatients who had taken any treatment , had any previous history of intolerance to the drug under study , had any abnormality in the laboratory investigation or who were immune compromised , pregnant or lactating , were excluded from the study .\nmoreover , patients with a history of tinea infections in family , friends , or close contacts were also excluded from the study .\na total of 100 patients satisfying all the inclusion criteria were included in the study .\nculture was performed simultaneously on sabouraud 's dextrose agar ( sda ) medium with chloramphenicol and sda with chloramphenicol and cycloheximide .\nall the enrolled patients were put on oral terbinafine 250 mg once daily for 2 weeks . no antacids or antihistamines were prescribed , and the patients were advised to take the medication at bedtime . no topical antifungals or antifungal steroid combination agents were allowed during the study . clinical examination and fungal culture\nwere repeated at the end of treatment period to document clinical and mycological cure , respectively .\nresidual pigmentation was present in some cases but was not taken as suggestive of incomplete cure .\npatients who had a persistent clinical disease on clinical examination were given alternate oral treatments and were excluded from further analysis .\ncases , in whom the disease was seen to be cured clinically , were advised to go for repeat cultures from the initial involved sites only .\nin addition , these clinically cured patients were asked to come for follow - up every 2 weeks .\nrelapse was defined as the appearance of lesions seen clinically and confirmed on culture subsequently .\nin this study , a total of 100 culture positive patients of tinea corporis and/or tinea cruris in age group of 1662 years were included in this study .\nthe disease was found to be more common in males , the male : female ratio being 1.63:1 ( 62 males and 38 females ) .\nthe majority of patients , i.e. , 63% were in the age group 2030 years .\nthe most common causative organisms grown on culture were trichophyton rubrum and trichophyton tonsurans [ table 1 ] .\nthe percentage distribution of various causative organisms involved at the end of oral terbinafine therapy , only 70 cases out of 100 were clinically cured while the rest ( 30/100 ) had signs of persistent infection at the treated site ( persisters ) . on repeat fungal culture ,\nfive cases out of the seventy clinically cured patients had a positive culture with the same organism that was grown initially .\nthus , out of a total of 100 cases enrolled , only 65% could achieve both clinical and mycological cure after 2-week terbinafine therapy ( cured ) . over the 12-week follow - up ,\nclinical relapse was seen in 22 of the 65 clinico - mycologically cured patients ( relapse ) .\nrelapse was confirmed on culture as the repeat cultures grew primary pretreatment isolates in all cases .\nthus , at the end of 12 weeks , there were only 43 cases out of the total 100 cases enrolled who were able to maintain a long - term clinical and mycological cure after 2 weeks of oral terbinafine treatment [ table 2 ] .\npercentage of causative organisms viz - a - viz the cured , persisters and relapse groups majority of the relapses ( 16/22 ) were seen after 8 weeks of completion of treatment .\nthis was followed by 3 more cases at the end of 4-week while further 2 , 6 , 3 , and 7 patients relapsed at 6 , 8 , 10 , and 12 weeks , respectively .\nthe mean percentage body surface area involvement in the cured , persistent , and relapse groups was 3.23 1.2% , 3.65 1.73% , and 3.182 1.46% , respectively .\nthus , there was no significant difference in the body surface area involvement when compared with the cured and the persistent disease groups ( mann whitney u - test , p : 0.3908 ) .\nfurthermore , there was no significant difference between the cured and the relapse group as far as the body surface area involvement is concerned ( mann whitney u - test , p : 0.5952 ) .\ndermatophytosis , being among the most common dermatologic conditions , does not spare people of any race or age . according to the world health organization , about 20% of the world population are affected by cutaneous dermatophytic infections .\ndermatophytes are related fungi capable of causing skin infection of the type known as ringworm or dermatophytosis .\nthe ringworm species belong to three asexual genera : microsporum , trichophyton , and epidermophyton , which attack the keratinized tissue and cause a wide spectrum of clinical manifestations , of which the most predominant type of infection is tinea corporis followed by tinea cruris , tinea pedis , and onychomycosis .\ntinea corporis accounts for about 70% of the dermatophytic infection . in this study , which was limited to cases with tinea corporis and/or tinea cruris we found tinea cruris with corporis was the predominant type seen in 52% of cases followed by tinea corporis only ( 28% ) and tinea cruris only ( 20% ) . in this study ,\n. and kumar et al . reported male : female ratio 1.86:1 and 1.36:1 , respectively , in patients with tinea infection .\nthe predominance of males is usually thought to be a result of increased physical activity and thus increased perspiration .\nthe patients belonged to the age group of 1462 years , with the mean age being 29.06 10.76 years .\nthe maximum number of patients , i.e. , 63% was in the age group 2030 years .\nin a recent study by surendran et al . from south india , a similar age statistics was seen .\nmoreover , multiple authors from various parts of india have reported comparable data on age distribution .\ntinea corporis and tinea cruris are most commonly caused by trichophyton species of which t. rubrum is most common infectious agent in the world accounting for around 50% of tinea corporis cases . in this study ,\nthe most common causative organism isolated after culture was t. rubrum , followed by t. tonsurans , trichophyton mentagrophytes , trichophyton verrucosum , and microsporum gypseum in that order . within the genus trichophyton ,\neven one study from northeast india reported t. tonsurans as the most common etiological agent in dermatophytosis .\ndiagnosis of tinea corporis and/or tinea cruris is mostly done clinically . to avoid a misdiagnosis , important for successful treatment , identification of dermatophyte requires both a fungal culture on sabouraud 's agar media and a mycological examination , consisting of a 1015% koh preparation , from skin scrapings . in our patients , koh slide test was positive in 94% of cases .\nhowever , much lower percentages of culture positivity in dermatophytosis have been reported by some authors .\nthe treatment is based on the infection site , an area involved etiological agent , and penetration ability of the drug .\nalthough topical antifungals may be sufficient for treatment of tinea corporis and/or tinea cruris , lesions which are widespread or fail to respond to topical therapy need systemic therapy . among the several systemic antifungal drugs used to treat dermatophytosis ,\nterbinafine 's fungicidal action , combined with its excellent pharmacokinetic properties , makes it an ideal systemic drug for the purpose .\nit exhibits its action on fungi by inhibiting the enzyme squalene epoxidase , thus causing an ergosterol deficiency which is important for fungal cell wall integrity .\nterbinafine is particularly effective against the species in trichophyton , microsporum , and epidermophyton genera , which in fact are the most common causative agents for tinea infections .\nhistorically griseofulvin was considered the drug of choice for tinea infections for a pretty long time .\nhowever , reports of higher relapse rates with griseofulvin pushed terbinafine to the forefront in treatment of tineacorporis and cruris . over the years\nterbinafine slowly gained a first line drug status in the treatment of tinea infections particularly tineacorporis and cruris where clinical and mycological cure rates were reported to be around 90% .\neven with an intermittent pulse dose therapy cure rates of around 90% have been reported with terbinafine .\nhowever , these results are in contrast to what we experienced in our patients of tinea cruris and corporis treated with oral terbinafine .\nwe found a clinical efficacy of only 43% in our patients followed for a 12-week .\nsuch a low clinical efficacy might be a result of the appearance of resistant strains of dermatophytes .\nalthough resistance to terbinafine in dermatophytosis is very uncommon in clinical practice , it has been reported in clinical isolates which result from sequence variation in the gene for squalene epoxidase .\nthese mutations ultimately decrease the affinity of the terbinafine binding domain resulting in decreased susceptibility to the drug . the low clinical efficacy\nas observed in this study could not be attributed to extensive body surface area involvement as there was no statistically significant difference between the cured , persistent and the relapsed cases . again\nnumerous authors have reported excellent results with oral terbinafine therapy in immunocompromised individuals who interestingly have extensive area involvement .\neven 1 week short course oral therapy with terbinafine has shown good results in such individuals with extensive skin area involvement .\nhowever , primary resistance to terbinafine in clinical t. rubrum strains has been reported long back .\nthus , we need to seriously consider the appearance of resistance to terbinafine in dermatophytes as an upcoming challenge in dermatological practice .\nour results demand further studies to characterize the resistant strains isolated , at a molecular and biochemical level and further test the susceptibility to various antifungals so that an alternate treatment could be proposed .\nthe main limitation of the study was the absence of calculation of mic in cases with failed cure and relapse .\nincomplete cure is very common after a 2-week course of oral terbinafine therapy and recommendations about the daily dose and duration of oral therapy need to be changed and updated accordingly .\nthis article highlights the presence of resistance to terbinafine in our cases of tinea infections .\nthis article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .\nthis article highlights the presence of resistance to terbinafine in our cases of tinea infections .\nthis article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .\nthis article highlights the presence of resistance to terbinafine in our cases of tinea infections .\nthis article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .", "answer": "background : the incidence of recurrent tinea infections after oral terbinafine therapy is on the rise.aim:this study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris.materials and methods : a total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study . \n the enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks . \n all clinically cured patients were then followed up for 12 weeks to look for any relapse / cure.results : the common dermatophytes grown on culture were trichophyton rubrum and trichophyton tonsurans in 55% and 20% patients , respectively . at the end of 2-week oral terbinafine therapy , \n 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture ( persisters ) at this time . \n these culture positive patients included all the clinically positive cases . \n rest of the patients ( 65/100 ) demonstrated both clinical and mycological cure at this time ( cured ) . over the 12-week follow - up , \n clinical relapse was seen in 22 more patients ( relapse ) among those who had shown clinical and mycological cure at the end of terbinafine therapy . \n thus , only 43% patients could achieve a long - term clinical and mycological cure after 2 weeks of oral terbinafine treatment . \n majority of the relapses ( 16/22 ) were seen after 8 weeks of completion of treatment . \n there was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured , persister , or relapse groups.conclusions:incomplete mycological cure as well as relapse is very common after standard ( 2-week ) terbinafine therapy in our patients of tinea cruris / corporis .", "id": 485} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbeyond its role of cellular energy currency and phosphate donor , atp plays a potent signaling role through its extracellular release and activation of cell surface purinergic receptors .\nfast responses to atp are mediated through activation of p2x receptors , a family ( p2x1p2x7 ) of atp - activated ligand - gated ion channels and metabotropic effects through the activation of p2y receptors ( p2y12 , p2y4 , p2y6 , p2y1114 ) which couple to heterotrimeric g proteins . human leukocytes including monocytes , mast cells , neutrophils and central microglia express a diverse repertoire of p2y receptors though p2x1 , p2x4 and p2x7 are the dominant p2x subtypes present .\nactivation of purinergic receptors in leukocytes is coupled to the production and secretion of cytokines and other pro - inflammatory molecules including prostaglandin e2 .\npurinergic receptors are associated with inflammation , with some receptors inhibited either directly ( p2y12 ) or indirectly through the activity of anti - thrombotic , in the case of platelet p2y12 , or anti - inflammatory agents , in the case of the action of statins on monocyte p2x4 .\natp can act as a non - peptide damage - associated molecular pattern ( damp ) release from injured cells and tissues . in this fashion\nthe release of cellular atp is unregulated and released due to cell lysis or puncture .\ncell surface purinergic receptors are activated by this atp damp signal which serves to initiate an inflammatory response and promote wound healing .\nhowever , atp can be released from cells physiologically and act as a critical signal for painful , inflammatory processes .\ndo release other nucleotides including utp and udp - sugars but our focus here is atp release . mechanisms of atp release during physiological processes remain diverse and controversial .\ninvestigation into how cellular stress stimulates atp release in non - leukocytes suggests roles for connexin and pannexin hemichannels , maxi- and volume - regulated anion channels and efflux through the p2x7 receptor , though release routes and signal transduction mechanism underlying atp release in leukocytes remain poorly defined .\nin neutrophils atp is released in response to activation of fmlp receptor by bacterially derived n - formylmethionine .\nthe precise release mechanism is unclear but occurs at the leading edge of migrating neutrophils .\nreleased atp and its subsequent metabolism to adenosine at the cell surface activate p2y2 and a3 receptors serving to direct cell orientation and promote migration in response to chemotactic signals .\nbacterially derived lipopolysaccharide can stimulate central microglia to secrete atp which in - turn activates neighboring astrocytes and modulates excitatory neurotransmission .\nthis raises the possibility that atp can act in a feed forward loop possibly amplifying responses to itself or other external cues which couple to atp secretion .\nfurthermore , such constitutive secretion leads to activation of cell surface gq - coupled p2y receptors which elevate intracellular calcium levels through release of calcium .\nthis mode of constitutive secretion generates a constant pericellular atp cloud or halo which appears to be important in regulating intracellular calcium homeostasis following p2y receptor activation . in cells of hematopoietic lineage such as monocyte / macrophage , nk killer and mast cells , secretory lysosomes have evolved as bifunctional organelles which combine classical degradative properties with secretion .\nthe mechanism of lysosomal atp transport remains undefined though a nucleotide transporter ( v - nut ) has been characterized for other atp containing vesicles .\nthe signal transduction coupling external cues such as cytokines , chemokines and bacterially derived molecules to atp release is poorly defined .\nwhat are the release machines in leukocytes and do they differ from other cell types ? it is expected that therapeutic intervention in agonist stimulated atp release is a potentially novel route to pharmacological modulation of innate immune responses but also in chronic inflammatory disease where normal inflammatory responses are heighten and act deleteriously .", "answer": "release and reception of extracellular atp by leukocytes plays a critical role in immune responses to infection , injury and cardiovascular disease . \n leukocytes of both the innate , adaptive immune and central nervous system express a repertoire of cell surface receptors for atp ( p2x and p2y receptors ) and its metabolites . \n atp acts as a damage - associated molecule pattern ( damp ) released by injured or dying cells . \n detection of released atp by neighboring leukocytes initiates inflammation and wound healing . \n however , recent evidence from our group and others suggests atp release by leukocytes themselves serves to regulate homeostatic mechanisms and coordinate responses to external pro - inflammatory cues . \n examples include the homeostatic control of intracellular calcium and regulation of migratory guidance during chemotactic response to external cues . \n though there has been some progress in elucidating atp release mechanisms of some mammalian cells types , release conduits and coupling signal transduction machinery remain larger elusive for leukocytes . \n our recent studies suggest a role for secretory lysosomes in releasing atp in monocytes . though poorly defined , \n targeting atp release mechanisms in leukocytes have great anti - inflammatory potential .", "id": 486} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npneumothorax is more frequent in the neonatal period than at any other time in life .\nsymptomatic pneumothorax occurs in 0.08% of all live births and 5% to 7% of infants with birth weight of below 1500\nthe development of a pneumothorax with ensuing hypoxia and hypercapnia is a potentially life - threatening event . to predict who will survive or die for newborns presenting with pneumothorax\ntraditionally a plain posteroanterior chest radiograph is the most appropriate method in the initial investigation .\nthe calculation of pneumothorax size on chest x - ray or computed tomography is a significant parameter for decision of treatment in adults .\nhowever , to our knowledge , the clinical significance of this calculation in neonates is still unknown .\ntherefore we aimed to investigate whether assessment of pneumothorax size on chest x - ray may be a predictor of prognosis in newborns .\nthis retrospective cohort study was performed on 60 newborns presenting with pneumothorax among 5929 infants admitted to our neonatal intensive care unit ( nicu ) from january 2007 to april 2011 .\nour institution is a tertiary hospital and its nicu has an annual admission of 1500 newborns .\nthe study was approved by the local ethics committee of tepecik teaching and research hospital .\nclinical data were collected from patients medical records including gestational age , birth weight , gender , type of delivery , apgar score , side of pneumothorax , mechanical ventilation , surfactant therapy , underlying lung pathology ( transient tachypnea of newborn , pneumonia , meconium aspiration syndrome ) , duration of hospitalization , time of diagnosis and need for chest tube .\nthe chest tube insertion was performed by the nicu physicians as soon as the clinical indication ( presence of acceptable respiratory distress , abnormal blood gas levels and cardiovascular instability ) was evident .\na common protocol for mechanical ventilation was performed by a positive pressure ventilator ( babylog 8000 plus , draeger , lubeck , germany ) .\nfio2 was given when it was needed to achieve arterial oxygen saturation between 85% and 95% by pulse oximetry .\ninspiratory time was set at 0.35 - 0.40 sec and positive end - expiratory pressure at 4 - 6 cmh2o according to the status of the patient .\nthe peak inspiratory pressure was set by the clinician to keep the blood gasses at the target range .\nthe newborns were switched from the assist / control mode to the simv mode for weaning on the basis of each infant 's blood gasses and clinical status .\nventilatory rate was then reduced using the simv mode of the ventilator . if newborns treated with fio2<30% tolerated it at a respiratory rate of 10 bpm , were extubated .\nthe calculation was done on the chest x - rays stored electronically in hospital picture archiving and communication system ( pacs ) .\npneumothorax size was calculated as the percentage of the widest transverse diameter of the pneomothorax area in the posteroanterior view to the widest transverse diameter of the thoracic cavity above the diaphragm .\nfischer 's exact test was used to compare categorical variables , mann - whitney u test for continuous variables and the wilcoxon rank sum test for ordinal variables .\nthe regression analysis was performed for evaluating the statistical significance of confounding variables . a receiver - operator characteristic ( roc ) curve\nwas used to explore various cut - off values of pneumothorax size . in order to determine whether the cut - off value was significant ,\nthis retrospective cohort study was performed on 60 newborns presenting with pneumothorax among 5929 infants admitted to our neonatal intensive care unit ( nicu ) from january 2007 to april 2011 .\nour institution is a tertiary hospital and its nicu has an annual admission of 1500 newborns .\nthe study was approved by the local ethics committee of tepecik teaching and research hospital .\nclinical data were collected from patients medical records including gestational age , birth weight , gender , type of delivery , apgar score , side of pneumothorax , mechanical ventilation , surfactant therapy , underlying lung pathology ( transient tachypnea of newborn , pneumonia , meconium aspiration syndrome ) , duration of hospitalization , time of diagnosis and need for chest tube .\nthe chest tube insertion was performed by the nicu physicians as soon as the clinical indication ( presence of acceptable respiratory distress , abnormal blood gas levels and cardiovascular instability ) was evident .\na common protocol for mechanical ventilation was performed by a positive pressure ventilator ( babylog 8000 plus , draeger , lubeck , germany ) .\nfio2 was given when it was needed to achieve arterial oxygen saturation between 85% and 95% by pulse oximetry .\ninspiratory time was set at 0.35 - 0.40 sec and positive end - expiratory pressure at 4 - 6 cmh2o according to the status of the patient .\nthe peak inspiratory pressure was set by the clinician to keep the blood gasses at the target range .\nthe newborns were switched from the assist / control mode to the simv mode for weaning on the basis of each infant 's blood gasses and clinical status .\nventilatory rate was then reduced using the simv mode of the ventilator . if newborns treated with fio2<30% tolerated it at a respiratory rate of 10 bpm , were extubated .\nthe calculation was done on the chest x - rays stored electronically in hospital picture archiving and communication system ( pacs ) .\npneumothorax size was calculated as the percentage of the widest transverse diameter of the pneomothorax area in the posteroanterior view to the widest transverse diameter of the thoracic cavity above the diaphragm .\nfischer 's exact test was used to compare categorical variables , mann - whitney u test for continuous variables and the wilcoxon rank sum test for ordinal variables .\nthe regression analysis was performed for evaluating the statistical significance of confounding variables . a receiver - operator characteristic ( roc ) curve\nwas used to explore various cut - off values of pneumothorax size . in order to determine whether the cut - off value was significant , sensitivity and specificity values were also calculated .\nof 60 newborns ( 1.0% ) presenting with pneumothorax among 5929 patients , 46 ( 76% ) were preterm and 14 ( 24% ) term .\npneumothorax was on the right side in 30 ( 50% ) newborns , on the left side in 21 ( 35% ) and bilateral in 9 ( 15% ) patients .\nof 46 preterm infants , 41 were on mechanical ventilation and 28 needed chest tube as overall 6 term infants on mechanical ventilation ( fig .\n1 ) . the flowchart of the study group patients characteristics are summarized in table 1 .\nthe mean gestational age of patients was 33.64.4 weeks and mean birth weight 2282909 g .\nof overall 60 newborns , 45 ( 75% ) were male and 15 ( 25% ) female .\nforty - three deliveries ( 71.6% ) were by cesarean section , and the remaining by vaginal delivery .\nseven patients ( 11% ) had transient tachypnea of the neonate , 10 ( 17% ) pneumonia and 27 ( 45% ) respiratory distress syndrome .\nthe cause of deaths included sepsis in immaturity and respiratory failure in 8 ( 44.4 % ) patients , sepsis in 5 ( 27.7% ) , severe intraventricular hemorrhage in 3 ( 16.6% ) and hypoxia in 2 ( 11.1% ) .\nfive patients ( 13.3% ) received prophylactic surfactant whereas 21 ( 35% ) received rescue therapy . \n demographics and patients characteristics ( n = 60 ) sd : standard deviation results of statistical analysis for prognostic significance of pneumothorax size calculated on chest x - ray and clinical parameters are summarized in table 2 .\npneumothorax size was significantly higher in non - survivors ( 31.12.8 vs. 16.41.4 , p<0.001 ) and also in patients treated with a chest tube ( 25.81.9 vs. 14.22.0 , p<0.001 ) .\nin addition , mortality discrimination was quantified by calculation of the area under the roc curve .\narea under the curve ( auc ) was 0.85 ( good discrimination by an area is 0.80 ) .\nthe cut - off point of pneumothorax size for predicting survival was determined as 20% .\nthe sensitivity of the calculation of pneumothorax according to the cut - off value was 72% whereas specificity was 83% .\nstatistical analysis of significance in predicting mortality data are presented as mean ( standard deviation ) the confounding factors including early gestational age , low birth weight , resuscitation at birth , mechanical ventilation and need for chest tube were of great significance in predicting mortality .\nhowever regression analysis revealed that only pneumothorax size was the independent prognostic factor ( p=0.02 ) .\nin contrast , other parameters such as gender , type of delivery , time of diagnosis did not show any statistical significance between survivors and non - survivors .\nin the present study we aimed to evaluate significance of pneumothorax size in predicting the mortality of newborns . the development of a pneumothorax with ensuing hypoxia and hypercapnia is a potentially life - threatening condition and 30% of the infants in the present study died in nicu .\nthis mortality rate is comparible with data in the literature of the last 20 years . even if not fatal , morbidity is a significant risk in these patients .\nthe risk for developing pneumothorax is increased in infants with respiratory distress syndrome , meconium aspiration syndrome , and pulmonary hypoplasia and in infants who need resuscitation at birth .\npulmonary disease is the underlying condition in 59 - 61% of neonates with pneumothorax . in our study pulmonary pathology\nthis finding can be explained by the fact that the majority of our cases were preterm . based on our findings\nwe think that low birth weight and preterm birth are the significant risk factors for developing pneumothorax .\ndevelopment of pneumothorax is increased in infants resuscitated with positive pressure ventilation and/or chest compression in the delivery room .\nthe pathogenesis is either the rupture of over distended alveoli during resuscitation or lung injury due to rib fracture fallowing chest compression .\nthree fourth of our cases had a history of mechanical ventilation which was more common in non - survivors like those who needed chest tube .\nalthough the risk factors related to mortality in the neonates presenting with pneumothorax are well - known , any practical method to predict who will survive or die is still of great importance in the clinical setting .\nthe diagnosis of pneumothorax is usually confirmed by imaging techniques which may also yield information about its size as well .\nthe size of pneumothorax on chest x - ray or computed tomography is a significant parameter in adults for treatment of the disease . to the best of our knowledge\n, there is no study in the english medical literature investigating the prognostic value of pneumothorax size in newborns .\nhowever the present study was carried out in a single large unit , therefore decreasing variation in the respiratory therapy was applied .\nthree dimensional lung volumes or lung pathologies like pneumothorax can be calculated by magnetic resonance imaging or computed tomography .\nalthough these techniques are more reliable than routine chest x - ray , they are less practical especially in clinically unstable patients like those in the nicu . in addition chest x - ray\nis also a less expensive method . because anteroposterior chest x - ray is a routine method , it is practical for the calculation of pneumothorax size in the nicu like assessment of cardiothoracic index and also reasonable for a retrospective study . in\nthe present study , calculation of pneumothorax size revealed statistical significance as a prognosticator in the neonatal period .\nthe pneumothorax size was significantly higher in non - survivors and appeared as an independent prognostic factor among the confounding variables .\nthe present study also showed that the neonates who had a pneumothorax size greater than 20% calculated by our method were likely to have worse prognosis .\nthe risk of mortality was 13 times higher in these newborns than in those with smaller pneumothorax size .\ncategorization of the patients according to the cut - off value appeared to show higher sensitivity and specificity .\nalthough pneumothorax is not a cause of death , patients with pneumothorax usually carry higher risk of death and related complications due to more severe clinical status .\nin conclusion development of pneumothorax in the neonatal period carries high risk of mortality especially in low birth weight and premature infants .\ntherefore identifying the risk groups by calculation of pneumothorax size can be a practical and reliable method .\nhowever further studies are in need to emphasize whether this method has a rationale to be used in clinical protocols .", "answer": "objectivepneumothorax in newborns may result in a significant mortality and morbidity . to predict who will survive or die is of great importance in the clinical management . \n the aim of this study is to address whether assessment of pneumothorax size on chest x - ray may be a predictor of prognosis in newborns presenting with pneumothorax.methodsof 5929 infants admitted to our neonatal intensive care unit ( nicu ) from january 2007 to april 2011 , 60 ( 1.0% ) newborns presenting with pneumothorax were included in the present study . \n pneumothorax size was calculated by measuring the widest transverse diameter of pneumothorax area in the posteroanterior view and dividing it by the widest transverse diameter of thoracic cavity above the diaphragm . \n clinical data were collected from the patients records.findingsoverall mortality rate was 30% ( 18 patients ) . \n pneumothorax size was significantly higher in nonsurvivors ( 31.12.8 vs 16.41.4 , p < 0.001 ) . \n the cut - off point of pneumothorax size for predicting survival was determined as 20% . \n the sensitivity was 72% whereas the specificity 83% . \n preterm birth , low birth weight , resuscitation at birth , need for mechanical ventilation and chest tube insertion were of great significance in predicting mortality . \n however , of overall significant parameters , only pneumothorax size was the independent prognostic factor by regression analysis ( p = 0.02)conclusionwe conclude that the calculation of pneumothorax size in the newborns is a predictor of prognosis with high sensitivity and specificity . \n furthermore newborns with pneumothorax size greater than 20% are likely to have worse prognosis .", "id": 487} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\neosinophilic chronic rhinosinusitis ( ecrs ) has been established as a subtype of chronic rhinosinusitis ( crs ) .\nit is characterized by a resistance to conventional treatment with long - term macrolides , and frequent recurrences develop unless treated by steroids.13 ecrs is common in asians . to make a diagnosis ,\nthe following must be examined : history of respiratory diseases ; imaging tests of the rhinosinuses ; laboratory data related to allergic reactions ; and histopathological tests.3,4 only one case of ecrs has been published that was associated with optic neuropathy , although several cases with optic nerve complications in cases of allergic fungal sinusitis have been reported.5,6 we have examined a case of ecrs with optic neuropathy probably caused by compression or inflammatory invasion of the optic canal by an expansion of the inflamed tissues . even though endoscopic surgery ( ess ) and steroid therapy were performed on the same day , the vision did not return .\na-68-year - old man noticed a sudden loss of vision in his right eye when he woke up .\nhe was examined in our hospital the same day and his best - corrected visual acuity ( bcva ) was no light perception in the right eye and 1.2 in the left eye .\nthe pupillary light reflex was almost absent in the right eye , and a relative afferent pupillary defect was present .\nfundus examination showed no optic disc edema and atrophy , and spontaneous venous pulsations were not present .\nthe macular area was normal , and optociliary shunt vessels were not present . from the clinical findings , we suspected a retrobulbar lesion and ordered an orbital computed tomography ( ct ) on the same day .\nhis history included nasal polypectomy more than 20 years earlier , and asthma that was not being treated .\nthe ct scan also showed pan - sinusitis , multilobular nasal polyps , and a defect of the sphenoid bone ( figures 1a c ) .\nthe laboratory data showed no elevation of the white blood cell count , eosinophilia , and c reactive protein .\nwe consulted an otorhinolaryngologist on the same day , and an emergency endoscopic sinus surgery ( ess ) was performed .\nintraoperatively , the ethmoid , maxillary , and sphenoidal sinuses were filled with highly viscous mucosal fluid . in addition , several polyps were found in the nasal cavity .\nafter excision of the polyps and thickened mucosa and drainage of the mucosal fluid , an erosion and thinning of the lateral wall of the sphenoid sinus bone and partial defects of the optic canal were found .\nthe optic canal was cleared to try to decompress the optic nerve , and betamethasone was applied to the exposed optic nerve to try to suppress the inflammatory changes .\nno fungal hyphae were detected by grocott and periodic acid schiff ( pas ) staining ( figures 2a d ) .\nunfortunately , the right visual acuity did not improve and remained at no light perception in spite of the postoperative betamethasone ( total 324 mg ) .\nsix months later , nasal polyps recurred and nasal administration of betamethasone was started and is currently being continued .\nthe laboratory data showed an elevation of total ige and eosinophils compared to that before the surgery ( before 1.2% and post - surgery 6.2% ) .\nthe specific iges against candida and aspergillus were negative with the radioallergosorbent ( rast ) test .\nchronic rhinosinusitis ( crs ) is a chronic inflammation of the rhinosinus mucosa and is characterized by the presence of two or more symptoms , viz . , nasal discharge , nasal obstruction , post - nasal drip , and reduction or loss of the sense of smell .\nthe diagnosis of crs is made by the signs and symptoms that remain for longer than 3 months and opacification of the sinus in x - ray and ct images .\nalthough crs is common , its subclassification , pathology , and treatment have still not been completely established .\ncases of crs have been divided into two groups ; chronic rhinosinusitis with nasal polyps ( crswnps ) and chronic rhinosinusitis without polyps ( crssnps ) in europe and the united states .\ncrswnps has a strong predisposition to recurrences even after ess , and pathological examinations show numerous eosinophils invading the mucosa .\nin contrast , crssnp is diagnosed by purulent changes , and histopathological examinations of the nasal polyps and nasal mucosa show lymphocytes and neutrophils as the dominant inflammatory invaders .\nhowever , some cases of crswnp in asians do not show eosinophil - dominant changes in the inflammation .\nin addition , this subtype is not fully resolved by conventional long - term macrolide therapy combined with surgical dissection of the mucosal membrane in the sinuses .\nthese cases have recently been classified as ecrs because they have different clinical characteristics from the more common crss that are associated with asthma , elevation of eosinophilic counts in peripheral blood , and massive invasion of eosinophils into the nasal mucosa .\nthe diagnosis of ecrs is finally determined by the clinical findings of chronic nasal symptoms , results of imaging tests , peripheral blood tests , and histological tests.4 our case had the nasal symptoms , history of nasal polypectomy , and asthma .\nct showed pan - sinusitis , and histopathological examination of removed mucosal membranes showed intensive invasion of eosinophils .\nfurthermore , there was a recurrence after surgery and steroid therapy . from the findings and clinical course , our case was diagnosed as ecrs and not the purulent type of crs . unlike the purulent type of crs , the ocular complications of ecrs have not been fully determined .\ngarg et al reported a case of ecrs associated with optic neuropathy.5 the mri images showed a high intensity area over the left intraorbital optic nerve without any lesions in the paranasal sinuses .\nthey treated their case with steroid therapy and radical sphenoethmoid clearance , however the visual acuity , which was light perception before treatment , improved only slightly to finger counting .\nfungi have received much attention in the united states as candidates for causing ecrs and allergic fungal rhinosinusitis ( afs ) .\nthe diagnostic criteria for afs include type 1 hypersensitivity to fungi , nasal polyps , and eosinophilic mucin containing fungi.7 it was suggested that fungi in the sinonasal mucosa might be the cause of non - atopic eosinophilia or local ige production.8 the clinical findings of afs overlap those of ecrs , and thus it is necessary to differentiate afs from ecrs .\ngenerally , cases with afs have unilateral lesions , elevation of eosinophils , and ige specific to fungal antigen .\nthe important findings for diagnosis of afs are the detection of hyphal forms of fungi and positive histopathological findings with pas or grocott staining . as with ecrs\n, afs is rarely associated with optic neuropathy.6 the orbital findings of afs are proptosis , ophthalmoplegia , optic neuropathy , and telecanthus .\nimaging tests show hyper - attenuating foci along with expansion and destruction of the sinus walls .\nmost cases of optic neuropathy have an erosion of the lateral wall of the sphenoid and optic canal.6 the incidence of bony erosion in afs is more than 12 times greater than in non - afs.9 whether an erosion of sphenoid bone occurs may determine the visual prognosis .\nthere is potential for mistaking the size of the lesion with only mri.10 mri of cases with allergic aspergillus sinusitis showed that the lesions were low intensity cystic lesions in both t1 and t2 weighted images .\nthus , the lesions may appear to be smaller than the actual size unless enhanced mri is used .\nby contrast , ct can accurately detect the area of hyper - attenuation and bone architecture .\nour case progressed to bilateral lesions , and the laboratory data were negative for ige specific to fungi .\nin addition , there were no hyphae in the biopsy sections with pas and grocott staining . from these findings\nit was not definitively determined why the visual acuity did not recover even though the ess was performed within 30 hours after the initial symptoms of optic neuropathy developed .\nour case presented with pan - sinusitis and thick mucosal membrane overall of the rhinosinus including the middle meatus and osteomeatal complex . although the inflammatory changes gradually enlarged after the polypectomy , the drainage from the parasinus might have been blocked leading to infection and inflammatory changes .\nthese changes could then cause the internal pressure in the parasinus to increase and affect the optic canal , even though bacterial infectious changes were not detected .\nin addition , local ischemia of the optic nerve might also have occurred secondary to the erosion of the optic canal followed by swelling of the optic nerve because the visual loss was so rapid . an earlier case of ecrs with optic neuropathy\nhad a different mri performed and an enhancement of the intraorbital optic nerve without extensive opacification of the rhinosinus was found .\nalthough we did not do mri , direct invasion by inflammatory tissues might have occurred in the right optic nerve as seen in the previous case . in conclusion , we documented a rare case of ecrs complicated by optic neuropathy\n. unfortunately , the visual acuity did not recover at all even though emergency ess and steroid therapy were performed .\nthese findings indicate that it is very important to suppress the allergic reaction for the prevention of ocular complications in ecrs cases .", "answer": "we report a case of eosinophilic chronic rhinosinusitis ( ecrs ) associated with optic neuropathy . \n the visual acuity in the right eye was suddenly reduced to no light perception on awakening in the morning . \n fundus examination of both eyes on the same day showed no remarkable changes . \n emergency computed tomography showed pan - sinusitis bilaterally and a partial defect of the sphenoid bone on the right side . from the clinical findings , the case was diagnosed as optic neuropathy associated with chronic sinusitis . \n endoscopic sinus surgery ( ess ) was performed on the same day , and all of the major sinuses were found to be filled with highly viscous fluid . \n part of the optic canal had a defect probably due to inflammatory invasion from the adjacent sphenoid bone . \n steroid therapy was started immediately postoperatively . \n histopathological examination of excised polyps showed that numerous eosinophils had invaded the polyps but no hyphae were present . \n the patient reported that he had bronchial asthma and had had nasal polypectomy . \n six months after the ess and steroid therapy , the patient had a recurrence of the sinusitis . at that time , laboratory examination showed an elevation of total ige and eosinophil numbers . from the clinical findings and course \n , this case was diagnosed as ecrs accompanied by optic neuropathy . \n although ecrs rarely has ocular complications , the inflammation can spread and the optic nerve can be affected .", "id": 488} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchronic obstructive pulmonary disease ( copd ) is presented mainly by bronchitis and emphysema in various combinations , often with asthmatic complications .\ndevelopment of cor pulmonale and/or upper respiratory infections may exacerbate the clinical outcome in chronic course of the disease .\nclinical examination as well as objective quantification of oxygenation is often critical for the clinical management of the patients .\narterial blood gas sample is often painful and carries the risk of local hematoma , infection and occlusion / embolization with consequent ischemic injury .\nhand - held pulse oximeters are usually applied in primary care due to small size , user - friendliness and affordable prices .\na meta - analysis of published studies has found a weighted mean correlation coefficient of 0.895 between the pulse oximetry and arterial blood sample .\nin addition , pulse oximetry can be used in the patients with acute respiratory insufficiency and in the follow - up of chronic respiratory conditions or acute exacerbations of copd .\nthe available literature suggests that the use of pulse oximetry for copd patients would be limited to acute events or specific situations .\nthe study was aimed to explore the association between spo2 and spirometer parameters of disease severity in copd patients with a view to identify whether the pulse oximetry can be used as an alternative to arterial values in the clinical management of copd patients in routine practice .\nthe study sample comprised of 31 patients diagnosed with copd , according to the criteria established by the global initiative for chronic obstructive disease ( gold ) who were consecutively referred to the respiratory outpatient clinic of a university hospital between may 2011 and december 2012 .\nall the patients were subjected to full medical history , general and local chest examination and chest x - ray .\nspo2 saturation was acquired for every patient using a portable pulse - oximetry device ( oxipen , envitecwismar , germany ) .\nthe percentage of hemoglobin oxygen saturation was measured after connecting the optical diodes on the patients fingers .\neach experiment was performed 3 times and the mean value was considered as the spo2 . in the next step ,\ndata regarding the spirometry [ forced expiratory volume in 1 second ( fev1 ) and forced vital capacity ] in all the patients were measured .\nbased on the gold criteria , copd was considered very severe ( gold iv ) if fevi / fvc < 0.7 and fev1 < 30% predicted or fev1\n< 50% predicted with respiratory failure or signs of right heart failure ; severe ( gold iii ) if 30 fev 50% ; moderate ( gold ii ) if 50 fev 80% , and mild ( gold i ) if the fev 1 /fvc ratio was < 70 and fev 1 80% of the predicted value ( 8) .\notherwise they were considered to have no lung disease ( normal ) or gold stage 0 if they reported respiratory symptoms .\nthe study complies with the declaration of helsinki and was approved by the institutional ethics committee of our university , and all patients gave written informed consent . for the statistical analysis , the shapiro - wilk test was used to determine the normality of the quantitative variables .\nthe data were expressed as median , interquartile range ; man - whitney u test and kruskal - wallis test were applied for quantitative comparison , and differences in categorical variables were examined using chi - square test .\nstatistical analysis was performed using an ibm computer and pasw software , version 18.0 ( spss , inc . ,\nthe study sample comprised of 31 patients diagnosed with copd , according to the criteria established by the global initiative for chronic obstructive disease ( gold ) who were consecutively referred to the respiratory outpatient clinic of a university hospital between may 2011 and december 2012 .\nall the patients were subjected to full medical history , general and local chest examination and chest x - ray .\nspo2 saturation was acquired for every patient using a portable pulse - oximetry device ( oxipen , envitecwismar , germany ) .\nthe percentage of hemoglobin oxygen saturation was measured after connecting the optical diodes on the patients fingers .\neach experiment was performed 3 times and the mean value was considered as the spo2 . in the next step ,\ndata regarding the spirometry [ forced expiratory volume in 1 second ( fev1 ) and forced vital capacity ] in all the patients were measured .\nbased on the gold criteria , copd was considered very severe ( gold iv ) if fevi / fvc < 0.7 and fev1 < 30% predicted or fev1\n< 50% predicted with respiratory failure or signs of right heart failure ; severe ( gold iii ) if 30 fev 50% ; moderate ( gold ii ) if 50 fev 80% , and mild ( gold i ) if the fev 1 /fvc ratio was < 70 and fev 1 80% of the predicted value ( 8) .\notherwise they were considered to have no lung disease ( normal ) or gold stage 0 if they reported respiratory symptoms .\nthe study complies with the declaration of helsinki and was approved by the institutional ethics committee of our university , and all patients gave written informed consent .\nfor the statistical analysis , the shapiro - wilk test was used to determine the normality of the quantitative variables .\nthe data were expressed as median , interquartile range ; man - whitney u test and kruskal - wallis test were applied for quantitative comparison , and differences in categorical variables were examined using chi - square test .\nstatistical analysis was performed using an ibm computer and pasw software , version 18.0 ( spss , inc . ,\nthe study was conducted on 31 patients with copd , including 24 males and 7 females ( mean age : 55.09 11.61 ; range : 35 - 76 years ) .\nthe pulse oximetry and spirometric variables of the patients are described in the table 1 .\nphysiological variables of the included patients there was not a significant association between fev1 % predicted and spo2 % ( p value > 0.05 ) , while there was a significant association between fev1/fvc % predicted and spo2 % ( r = 0.556 , p value < 0.001 ) [ figures 1 and 2 ] .\nthe dotted curves represent the 95% confidence intervals of fev1% for a given spo2% correlation between fev1/fvc% predicted and spo2% in the included patients .\nthe dotted curves represent the 95% confidence intervals of fev1/fvc% for a given spo2% in addition , the association among age with spo2% , fev1% predicted and also fev1/fvc % predicted was not significant statistically ( p value > 0.05 ) .\nthe median fev1 % predicted in the stage 0 was [ median 90% , interquartile range ( 90%-95% ) ] ; stage i was 83% , 75%-89% ; stage ii was 62% , 51%-79% ; stage iii was 45% , 38%-48% and also stage iv was 27% , 21%-33% , which was a significant differences among them in five stages of gold using kruskal - wallis test ( p value < 0.05 ) .\nthe median fev1/fvc % predicted in the stage 0 was [ median 74% , interquartile range ( 73%-89% ] ; stage i was 72.5% , 69%-78% ; stage ii was 70% , 58%-79% ; stage iii was 56% , 52%-70 % and also stage iv was 57.5% , 47%-68% , which was a significant differences among them in five stages of gold ( p value < 0.05 ) .\nthe median spo2% in the stage 0 was [ median 94% , interquartile range ( 93%-97% ) ] ; stage i was 94.5% , 91%-99% ; stage ii was 92% , 86%-96% ; stage iii was 90% , 74%-96% and also stage iv was 93.5% , 93%-94% , which was not a significant differences among them in five stages of gold ( p value > 0.05 ) .\ncopd is the sixth prominent cause of death in the world , and is estimated to be the third killing and the fifth debilitating disease by the year 2020 .\ndirect measurement of the pulmonary function ( spirometry ) and arterial blood gas ( abg ) analysis are indicated for the clinical management of copd . although pulse oximeters are extensively used in emergency departments , anesthesiology , and critical care , data on their efficacy in general practice is limited . in this regard\n, studies have shown that these devices are only reliable when saturation is < 80% .\nwe aimed to investigate the effectiveness of pulse oximetery for the determination of severity of copd and respiratory failure .\nthe study showed no correlations between the disease severity ( in terms of baseline airflow obstruction ) and spo2 in copd patients .\nthe recruited patients in the current study mostly have a stable condition and came to the clinic for their routine follow - up .\nthis finding is in line with a number of studies that have documented a low degree of accuracy for the noninvasive assessment of saturation in stable copd patients .\nstudied the application of pulse oximetry in 88 patients with deteriorating copd which spearman correlation coefficient for the association between baseline fev1% predicted as documented in the patient 's medical file and spo2 was r = 0.55 ( p = 0.002 ) for the patients with acute exacerbations . on the other hand , in 207 patients with stable copd , a weak correlation existed between post - bronchodilator fev1 % predicted and spo2 values ( spearman r = 0.19 , p = 0.006 ; for current smokers : r = 0.13 , p = 0.252 and for former smokers ; r = 0.19 , p = 0.047 ) . also , median spo2 values did not differ between gold stages ( median test : p = 0.079 ) .\nthese observations suggest that pulse oximetry is mainly helpful when the symptoms are deteriorated because of severe airflow obstruction ( fev1 % predicted < 50% ) .\nthis is consistent with the findings of previous studies indicating that the rate of tests with spo2 < 92% increases when the fev1 % predicted value is < 50% in stable copd patients .\nit is noteworthy that our population was consisting of those suffering from mild to severe copd who came to an outpatient clinic .\ntherefore , the findings of this study may be different from those acquired in hospital - based studies . in this regard , a turkish study in the patients with severe copd demonstrated a high sensitivity for both spo2 and fev1 in reflecting hypoxemia and hypercapnia ( 83.9 and 90.3% , respectively ) .\nalthough monitoring of saturation is recommended only for patients with severe disease , pulse oximetry can identify those who might benefit from oxygen therapy or pulmonary rehabilitation .\nmeanwhile , overestimation of arterial oxyhemoglobin saturation might occur in spo2 values < 80% , especially in the patients with darkly pigmented skin .\noxygen saturations are not helpful for the diagnosis of copd ; saturations of < 98% provides a sensitivity of 79% , but specificity of only 37% .\nhowever , pulse oximetry may help in determining the criteria for long - term oxygen therapy or the need for referral to hospital in acute exacerbations . according to dutch family practice guidelines , if pulse oximetry shows spo2\nmoreover , initiation of oxygen therapy based on an oxygen saturation value < 90% is considered another possible application for pulse oximetry in the primary care .\nalthough the current oximeters are practically accurate , they may produce false data in the presence of carboxyhemoglobinemia , hemodynamic instability , dark skin pigmentation , jaundice , and also during the exercise .\nthe oximeter - indicated saturation may significantly overestimate arterial po2 , if the patient is alkalemic .\nfurthermore , the study depicted a significant association between fev1/fvc% predicted and spo2% ( r = 0.556 , p value = 0.001 ) .\nthe fev1/fvc ratio , also called tiffeneau - pinelli index , is a calculated ratio for the diagnosis of obstructive or restrictive lung disease .\nit represents the proportion of a person 's vital capacity that is exhaled in the first second of expiration .\nthe above - mentioned finding was observed in nomori et al . on 83 patients who underwent lobectomy for lung cancer .\na number of studies have showed that fev1/fvc depends significantly on age in healthy subjects .\nhowever , the current study did not show the correlation in the copd patients , which could be due to small number of the included cases in our study .\nfurther a larger study may clarify such association in copd patients . in this study the mean age was 55.09 11.61 years with no significant relationship between age and fev1% of predicted in copd patients , and this was matching with the previous studies .\nfurthermore , the current study may demonstrate that fev1 is essential for the diagnosis and quantification of the respiratory impairment resulting from copd .\nbut , fev1 is known to poorly correlate with symptoms , quality of life exacerbation frequency and exercise intolerance . in total , the study did not support that oxygen saturation measured by pulse oximetry to replace analysis of an arterial blood gas sample in the clinical evaluation of oxygenation in health care patients with copd .\nunfortunately , we did not include a standardized assessment of dyspnoea in our study , which would have enabled us to investigate the relationship between the severity of dyspnoea and spo2 .\nanother limitation is that we did not measure arterial blood gas components , such as pao2 , which would have allowed us to acquire more comprehensive results .\nhowever , these findings support the claim that spirometric parameters , but not spo2 level , could be useful indicators of the patient outcome , although further evidence needs to be obtained .\nthe study may demonstrate that oxygen saturation measured by pulse oximetry appears to be independent of the degree of airways obstruction as quantified by the fev1 ; although further evidence needs to be assessed these preliminary findings .", "answer": "background : the study was aimed to explore the association between arterial oxygen saturation ( spo2 ) and spirometer parameters of disease severity in chronic obstructive pulmonary disease ( copd ) patients with a view to identify whether the pulse oximetry can be used as an alternative to arterial values in the clinical management of copd patients in a routine practice.materials and methods : thirty - one patients with copd were included in this study . \n after evaluation of each patient through history taking , physical examination and chest x - ray , spo2 % and data regarding spirometry ( fev1% predicted and fev1/fvc % predicted ) in all patients were measured . \n linear correlations among the variables were analyzed using the regression analysis.results:in total 31 copd patients according to the criteria established by the global initiative for chronic obstructive disease ( gold ) were included in the study . \n there was not statistically significant correlation between fev1 % predicted and spo2 values ( p > 0.05 ) , but a great correlation existed between fev1/fvc % predicted and spo2 values ( r = 0.556 , p < 0.001 ) . \n median spo2 values did not differ between gold stages ( kruskal - wallis test : p = 0.17).conclusion : the study may demonstrate that oxygen saturation measured by pulse oximetry appears to be independent of the degree of airways obstruction as quantified by the fev1 ; although further evidence needs to be assessed these preliminary findings .", "id": 489} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe unfortunate complication of a colotomy resulting from a colonoscopic polypectomy can be disastrous . using the versatility of laparoscopic surgery\nwe report a case of cecal perforation , in a 70 year old female , following colonoscopic polypectomy that was treated successfully with laparoscopic application of an endo - gia linear stapler .\nfour months following staple resection of her cecal perforation , the patient is asymptomatic and has undergone a repeat colonoscopy without any sequelae .\nlaparoscopic techniques can be safely applied in the treatment of colonic perforations following therapeutic polypectomies .\na suggested management algorithm is provided highlighting the role laparoscopy may provide in selected patients .\ncolon perforation during therapeutic colonoscopy has been estimated to occur at a rate of approximately 0.1% to 0.3% .\nperforation may occur through a variety of mechanisms , including energy application at the polyp site , direct mechanical trauma from the tip of the endoscope , lateral pressure from the side of a bowed endoscope , and pneumatic injury from overinsufflation .\nseveral case reports advocating laparoscopic repair of colonic perforation following colonoscopy have been described in the literature . in our present case report\n, we discuss the single application of an endoscopic linear stapler to close the perforation while preserving colonic lumen integrity in the presence of endoscopically placed mucosal clips .\na 70-year - old caucasian female with a past medical history significant for sigmoid diverticulosis and previous benign polyps of the colon was found to have a lipomatous lesion in the ascending colon during routine surveillance colonoscopy .\na complete resection of the polyp was performed using a 15-ml saline injection with india ink lift and a hot snare .\nafter resection , the mucosal biopsy site was larger than anticipated , and it became difficult to maintain insufflation .\nthe procedure was halted secondary to progressive abdominal pain and the clinical suspicion of a colonic perforation .\nthe perforation was confirmed with the presence of substantial free air on radiographs . in this rare situation of early discovery and hemodynamic stability ,\nthe patient was taken immediately to the operating room for surgical repair . in the operating theater ,\npneumoperitoneum was established with a veress needle , and a 5-mm camera with an optical access trocar was placed in the left lower quadrant . of note , the abdominal pressure at initial access was measured at 10 mm hg , consistent with pneumoperitoneum from insufflation through the colotomy .\na 5-mm anterior perforation of the cecum was clearly visible with an area of circumferential coagulation extending approximately 2 mm ( figure 1a ) .\nthe cecum was noted to be adhered to the side wall , and hence one additional 5-mm port and one 10-mm port were placed for mobilization in the midline .\nthe ports were placed in the umbilicus and the suprapubic position . after a sufficient segment of the cecum was freed , a single 30 silk stitch was placed to provide temporary closure and to provide a handle for elevation of the cecum .\nan endo - gia 60-mm blue load was applied to preserve the lumen of the cecum while incorporating the entirety of the defect including the area of coagulation necrosis ( figure 1b ) .\nthe suture line incorporated healthy pink mucosa with preservation of the colonic lumen ( figure 1c ) .\nthe patient had an uncomplicated recovery with discharge on hospital day 4 . at the 4-month follow - up ,\nthe patient is without any complaints , tolerating a regular diet , and at baseline health .\nshe has had an interval surveillance colonoscopy without any abnormalities and a well - healed polypectomy / surgical site .\na : anterior cecal perforation with surrounding circumferential area of necrosis and endoscopically placed clips ( white arrows ) .\nb : endo - gia 60 mm stapling with careful preservation of colonic lumen with incorporation of the entirety of the defect and area of coagulation necrosis .\ncolotomy that occurs during colonoscopy is a specialized subset of colon perforations for a variety of reasons . to begin with , in many cases\nthe patient is under the care of a physician in a monitored setting with established intravenous access .\nalthough there may be some question as to the precise benefits of mechanical preparation in elective colorectal surgery , in the emergent setting it may be advantageous in minimizing the amount of gross spillage .\nin addition , the endoscopist may provide localization of the suspected injury , allowing for more directed treatment .\nit has been advocated by some that colonoscopic polypectomy should be performed in conjunction with laparoscopy when a particularly difficult or suspicious polyp is anticipated . in keeping with the success of previous case reports and advances in minimally invasive techniques , we propose an active role of laparoscopy in complex colonoscopies as outlined in figure 2 .\nperforations , depending upon their size , may be treated with direct suturing , staple resection or segmental resection .\nour approach to this cecal perforation was fundamentally the same as that for an appendectomy .\nthe technical skills involved in the procedure are well within the capabilities of practicing general surgeons , but several technical tips merit further comment . in this case , primary repair with intracorporeal suturing was technically possible .\nhowever , it seemed ill advised , given the visible zone of coagulation necrosis surrounding the defect . in regards to the surgical stapler\n, it would have been technically easier to place a single firing across the cecum rather than 2 angled applications ; however , 2 factors suggested multiple stapling : the endoscopically placed clips may have interfered with proper staple line creation , and a single firing raised the concern for luminal compromise .\nit may be argued that in this case the procedure was effective , but that minimally invasive techniques are not broadly applicable .\nhowever , in the analogous situation of perforated appendicitis , there have been multiple studies in which laparoscopy does not have an increased rate of complications over open laparotomy .\nconceptually , it seems there is little harm in starting with a diagnostic laparoscopy and proceeding based on the nature of the injury and the experience of the surgeon .\nmany general surgeons will be confronted with the problem of colon perforation during colonoscopy . in the case\npresented here , we modified the established technique of laparoscopic appendectomy to the specific problem of cecal perforation and have demonstrated the feasibility of such an approach .", "answer": "background and objectives : the unfortunate complication of a colotomy resulting from a colonoscopic polypectomy can be disastrous . using the versatility of laparoscopic surgery \n , we aim to provide a treatment algorithm for these colonoscopic perforations.methods:we report a case of cecal perforation , in a 70 year old female , following colonoscopic polypectomy that was treated successfully with laparoscopic application of an endo - gia linear stapler.results:four months following staple resection of her cecal perforation , the patient is asymptomatic and has undergone a repeat colonoscopy without any sequelae.conclusions:laparoscopic techniques can be safely applied in the treatment of colonic perforations following therapeutic polypectomies . \n a suggested management algorithm is provided highlighting the role laparoscopy may provide in selected patients .", "id": 490} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na malignant peripheral nerve sheath tumor ( mpnst ) is a sarcoma that arises from peripheral nerves or cells of the associated nerve sheath ( schwann cells , perineural cells , fibroblasts ) .\nthe term \" mpnst \" has substituted previously used terms such as malignant schwannoma , neurofibrosarcoma , and neurogenic sarcoma1,2 ) .\nthe mpnsts comprise approximately 5% to 10% of all soft tissue tumors and have an incidence of 0.001% in the general population and the etiology is unknown .\nhowever , more than half of mpnst cases develop in patients with neurofibromatosis type-1 ( nf-1 ) and there is a higher incidence in patients that have undergone prior radiotherapy1,2,5,8,13 ) .\nmpnsts are most likely to metastasize to the lungs , followed by the bone and finally the pleura , but , spinal cord and brain metastasis is very rare in non - nf-1 mpnst3,7 ) .\nthe authors report a very rare case of spinal cord and brain metastasis of mpnst in the lumbar spine that occurred in a 18-year - old man without nf .\nan 18-year - old man presented initially with a 6-month history of low back pain that worsened over time .\none month prior to admission , the patient developed radiating pain to his anterior thigh .\nneither caf au lait spots nor neurofibromas were seen and his family history was absent of nf-1 .\nthe neurologic examination showed normal motor power in his lower extremities . magnetic resonance imaging ( mri ) showed a paraspinal mass that extended from the central space of l2 to the right psoas muscle through right l2 - 3 foraminal space .\nit was an asymmetrical dumbbell shaped mass and the thecal sac was displaced left by the mass .\nthe mass showed iso - signal intensity on t1-weighted images and mixed signal intensity on t2-weighted images .\na paramedian incision was made from the l1 to l4 and we exposed the right l2 and l3 lamina with transverse process .\nright l2 hemilaminectomy was performed using a high speed drill and kerrison rongeur to expose the thecal sac .\nthe margin of mass was relatively distinct from neural tissue , thus gross total resection was possible under microscopic view . to remove the mass extended to the psoas muscle ,\nthe right transverse process of l2 and l3 was resected and the mass was visible .\nafter the operation , his symptom had improved . however , a few days later , his confirmed pathologic report was presented as mpnst ( fig .\nthe contrast - enhanced mri was followed at 1 month after the operation and revealed a total removal of tumor ( fig .\nhowever , the patient declined the external beam radiation due to the fear of potential radiation risk .\nspine and brain mri showed that the tumor recurrence with leptomeningeal , multiple spinal cord and brain metastases ( fig .\n4 ) . complete surgical clearance of the tumor was not technically feasible , owing to the multiple metastases .\ntherefore , the patient was referred for adjuvant chemotherapy . in addition , intrathecal chemotherapy was performed .\nafter 4 months of chemotherapy , he was referred to the hospice hospital and died within a month .\nan 18-year - old man presented initially with a 6-month history of low back pain that worsened over time .\none month prior to admission , the patient developed radiating pain to his anterior thigh .\nneither caf au lait spots nor neurofibromas were seen and his family history was absent of nf-1 .\nthe neurologic examination showed normal motor power in his lower extremities . magnetic resonance imaging ( mri ) showed a paraspinal mass that extended from the central space of l2 to the right psoas muscle through right l2 - 3 foraminal space .\nit was an asymmetrical dumbbell shaped mass and the thecal sac was displaced left by the mass .\nthe mass showed iso - signal intensity on t1-weighted images and mixed signal intensity on t2-weighted images .\na paramedian incision was made from the l1 to l4 and we exposed the right l2 and l3 lamina with transverse process .\nright l2 hemilaminectomy was performed using a high speed drill and kerrison rongeur to expose the thecal sac . for removal of intradural portion\nthe margin of mass was relatively distinct from neural tissue , thus gross total resection was possible under microscopic view . to remove the mass extended to the psoas muscle ,\nthe right transverse process of l2 and l3 was resected and the mass was visible .\nafter the operation , his symptom had improved . however , a few days later , his confirmed pathologic report was presented as mpnst ( fig .\nthe contrast - enhanced mri was followed at 1 month after the operation and revealed a total removal of tumor ( fig .\nhowever , the patient declined the external beam radiation due to the fear of potential radiation risk .\nspine and brain mri showed that the tumor recurrence with leptomeningeal , multiple spinal cord and brain metastases ( fig .\n4 ) . complete surgical clearance of the tumor was not technically feasible , owing to the multiple metastases .\nin addition , intrathecal chemotherapy was performed . however , no significant effect was observed and the patient 's condition deteriorated gradually .\nafter 4 months of chemotherapy , he was referred to the hospice hospital and died within a month .\nnon - nf-1 mpnsts are very rare and the occurrence of mpnsts occurring in adolescents is very rare\n. mpnsts generally occur in adulthood typically between the ages of 20 and 50 years of age .\napproximately 10 - 20% of cases have been reported to occur in the first 2 decades of life , with occasional cases involving infants as young as 11 months of age5,6 ) .\nhruban et al . described 43 patients with mpnst and of these patients , 28 ( 65% ) had distant metastasis3 ) .\nsites of metastasis included the lungs ( 22 cases ) , bone ( 9 cases ) , pleura ( 6 cases ) , retroperitoneum ( 4 cases ) , diaphragm ( 3 cases ) , inguinal lymph nodes ( 2 cases ) , liver ( 2 cases ) , chest wall ( 2 cases ) , soft tissue ( 2 cases ) , pulmonary hilum , pericardium , thyroid gland , and adrenal gland ( 1 case each ) .\ndescribed 11 distant metastasises in 54 patients with mpnst that included metastases to lymph nodes , pleura , lung , liver , adrenal gland , leptomeninges and brain7 ) .\nwilliam et al.4 ) reported a non - nf-1 mpnst case of metastasis to the spinal cord4 ) .\nour case showed that leptomeningeal , spinal cord and brain metastasis of non - nf-1 mpnst for relatively short period after tumor removal in young male patient , reflecting aggressive nature of this malignancy .\nthe outcome with respect to both local recurrence and distant metastasis largely depends on grade of surgical excision .\nradiation therapy combined with wide surgical excision offers statistical significant reduction in the rates of local disease recurrence .\nhowever , it has not had a meaningful reduction in either rate of distant metastasis or overall survival15 ) .\nbenefit of chemotherapy is unproven and its application is limited to high grade metastatic disease3 ) .\nthe italian and german soft tissue sarcoma cooperative group reported an overall pediatric response rate of 45% , with the highest response noted within the ifosfamide group9,11,12 ) .\nthe recurrence rate for mpnsts has been reported to range from 40 - 68%7,10,14 ) .\nthe 5-year survival rate has been reported at 16 - 52% and a favorable prognosis has been related with complete surgical excision of the tumors that are sized less than 5 cm7,10 ) .\nhistorically , mpnsts have been difficult tumors to treat due to their inherently aggressive nature and dismal prognosis .\nour patient underwent complete surgical excision , but the patient was not treated with radiotherapy .\nfollow - up images revealed multiple spinal cord and brain metastases . the patient was managed with chemotherapy , but expired several months later . despite complete surgical excision ,\nwe reported a case of mpnst that had metastasized to the brain and spinal cord .\nbecause the mpnst showed both rapid and aggressive progression , patients should be followed carefully to identify local recurrence or metastasis and be mandatory an adjuvant radiotherapy .", "answer": "a malignant peripheral nerve sheath tumor ( mpnst ) is a type of sarcoma that arises from peripheral nerves or cells of the associated nerve sheath . \n this tumor most commonly metastasizes to the lung and metastases to the spinal cord and brain are very rare . \n we describe a case of young patient with spinal cord and brain metastases resulting from mpnst . \n an 18-year - old man presented with a 6-month history of low back pain and radiating pain to his anterior thigh . magnetic resonance imaging showed a paraspinal mass that extended from the central space of l2 to right psoas muscle through the right l2 - 3 foraminal space . \n the patient underwent surgery and the result of the histopathologic study was diagnostic for mpnst . \n six months after surgery , follow - up images revealed multiple spinal cord and brain metastases . \n the patient was managed with chemotherapy , but died several months later . despite complete surgical excision , \n the mpnst progressed rapidly and aggressively . \n thus , patients with mpnst should be followed carefully to identify local recurrence or metastasis as early as possible .", "id": 491} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n drug reaction with eosinophilia and systemic symptoms ( dress ) is a life - threatening reaction that necessitates determination and discontinuation of the offending drug.the aromatic structure of teicoplanin is shared by most other medications involved in dress.the use of additional treatment including intravenous immunoglobulins , corticosteroids and antivirals is generally based on experience rather than proven benefits drawn from well - designed clinical trials . \n\ndrug reaction with eosinophilia and systemic symptoms ( dress ) syndrome is defined as an idiosyncratic , rare , and life - threatening reaction .\nthe clinical features of the syndrome , including fever , rash , facial edema , lymphadenopathy , hematological abnormality , and internal organ involvement , arise 1030 days following drug exposure .\nthis late onset of symptoms discriminates dress from some other drug - induced skin reactions such as erythema morbilliform [ 1 , 2 ] .\nthe most common suspected medicines causing dress include aromatic anticonvulsants ( carbamazepine , phenytoin , phenobarbital , and lamotrigine ) , allopurinol , and antibiotics ( sulfasalazine , vancomycin , and minocycline ) . to the best of our knowledge ,\nthere are limited reports of teicoplanin - induced dress in the literature [ 26 ] . here\na 37-year - old woman was admitted to hospital with redness and edema of inguinal area . the involved area was tender and warm on examination . with a presumptive diagnosis of cellulitis ,\nafter 24 h , due to the acceptable clinical state of the patient , treatment was planned to be completed in the ambulatory setting .\nvancomycin was replaced with teicoplanin , considering its ease of administration as an intramuscular injection ( 400 mg every 12 h for three doses , then 400 mg daily ) . on the 14th day of treatment ,\nthe patient developed generalized maculopapular rash ( fig . 1 ) , accompanied by fever ( 39 c ) , wheezing , shortening of breath , and cervical and axillary lymphadenopathy .\nlab tests revealed abnormal liver enzymes [ alanine aminotransferase ( alt ) 134 iu / l , aspartate transaminase ( ast ) 141 \niu / l ] , leukocytosis ( white blood cell count 17,000/l ) with eosinophilia to more than 8% ( 1360/l ) , a blood urea nitrogen ( bun ) value of 24 mg / dl , and a serum creatinine ( scr ) value of 0.8 mg / dl .\nthe follow - up lab test performed 1 month later indicated resolution of liver dysfunction ( alt 22 u / l , ast 18 u / l).fig . \n1generalized maculopapular rash on the neck and trunk \n generalized maculopapular rash on the neck and trunk\nwith respect to diversity in scoring systems and differential diagnoses , the exact incidence of dress , as a life - threatening skin reaction , remains unknown . this could be partially because there is no gold - standard test for diagnosis of dress , and as a result , the diagnosis remains a challenge and is mainly based on conventional proposed scoring systems .\nthe most common scoring systems to stratify dress are regiscar , the japanese group s criteria for diagnosis of dress / drug - induced hypersensitivity syndrome ( dihs ) , and a system proposed by kardaun et al . \n( table 1).table 1kardaun et al.s scoring system reproduced from kardaun et al .\n, with permissionitempresentabsentpatient s scorefever 38.5 c ( 101.3 f)010enlarged lymph nodes ( > 1 cm size , at least two sites)101eosinophilia : 700 or 10% ( leucopenia ) ; 1500 or 20% ( leucopenia)1 ; 201atypical lymphocytes100rash 50% of body surface area101rash suggestive ( 2 of facial edema , purpura , infiltration , desquamation)100skin biopsy suggesting alternative diagnosis100organ involvement : 1 ; 21 ; 202disease duration > 15 days020investigation for alternative cause ( blood cultures , ana * , serology for hepatitis viruses , mycoplasma , chlamydia ) , 3 done and negative100total score5total score < 2 : excluded ; 23 : possible ; 45 : probable ; 6 : definite*ana antinuclear antibody \n kardaun et al.s scoring system reproduced from kardaun et al . , with permission total score < 2 : excluded ; 23 : possible ; 45 : probable ; 6 : definite * ana antinuclear antibody dress is classified as a type iv drug - induced hypersensitivity reaction that is characterized by delayed onset of symptoms .\nthe rising of eosinophil count and non - necrotizing lesions differentiate dress from other type iv drug - induced hypersensitivity reactions such as stevens - johnson syndrome / toxic epidermal necrolysis ( sjs / ten ) . in regard to delayed onset of signs and symptoms including skin rash ( more than 50% of body surface area ) , fever ( more than 38.5 c ) , and enlarged lymph node ( more than 1 cm in two sites ) , dress was highly suspected .\nthese findings are in concordance with previous reports of teicoplanin - induced dress [ 3 , 4 , 6 ] .\nadditional work - up was performed to evaluate hematological abnormalities and organ involvement , which revealed leukocytosis with eosinophilia and liver involvement .\nchest x - ray or computerized tomography ( ct ) scan and skin biopsy were not performed due to patient non - compliance .\ntesting for human herpesvirus-6 , human herpesvirus-7 , and epstein - barr virus antibodies was not requested because of limited resources . in general , our presumptive diagnosis was mainly based on clinical signs and symptoms and accessible lab tests . on the basis of the scoring systems mentioned above , the reaction was rated as probable ( score = 4 ) according to regiscar and possible ( score = 5 ) according to kardaun et al.s scoring system . since presence of atypical lymphocytes and reactivation of human herpesvirus were not investigated ,\ndress was not confirmed by the japanese group s criteria for diagnosis of dress / dihs .\nthe aromatic structure of vancomycin and teicoplanin may explain the occurrence of dress with these agents . in this case ,\nteicoplanin was used instead of vancomycin according to the summary of product characteristics ( available at http://www.sanofi.com.au ) . given the similar structure of vancomycin and teicoplanin ,\n. the implementation of additional treatment including intravenous immunoglobulins , corticosteroids and antivirals is generally based on experience rather than proven benefits drawn from well - designed clinical trials [ 1113 ] .\nadministration of corticosteroids in severe pulmonary involvement seems to be reasonable according to results from some studies [ 13 , 14 ] .\nhowever , we did not implement these interventions , considering the lack of proven benefit and the patient s overall state of health .\nsholeh ebrahimpour , mehdi mohammadi , and kheirollah gholami declare that they have no conflicts of interest relating to the content of this article .", "answer": "intramuscular teicoplanin ( 400 mg every 12 h for three doses , then 400 mg daily , intramuscularly ) was prescribed for a 37-year - old woman with presumptive diagnosis of cellulitis . on the 14th day of treatment , she developed generalized maculopapular rash , accompanied by fever , wheezing , shortening of breath , and lymphadenopathy . \n lab tests revealed abnormal liver enzymes , leukocytosis , and eosinophilia . \n the treatment was interrupted with suspicion of drug reaction . \n fever subsided after 48 h. skin eruption and respiratory symptoms began to resolve within 2 weeks . \n the follow - up lab tests performed 1 month later indicated resolution of liver dysfunction . \n with respect to delayed onset of symptoms including fever , generalized rash , lymphadenopathy , and organ involvement , drug reaction with eosinophilia and systemic symptoms ( dress ) was highly suspected . \n the causality was evaluated by conventional scoring systems . \n the reaction was rated as probable ( score = 5 ) according to regiscar and possible ( score = 5 ) based on kardaun et al.s scoring system . \n however , dress was not confirmed by the japanese group s criteria for diagnosis of dress / drug - induced hypersensitivity syndrome ( dihs ) .", "id": 492} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\neccentric exercise was shown to provoke skeletal muscle damage leading to delayed onset of \n muscle soreness ( doms)1,2,3 .\nacute muscle damage can \n cause discomfort at the site of injury , inflammation , oxidative stress , edema , and loss of \n muscular function and strength4 , 5 .\nmany researchers have attempted to ameliorate symptoms by \n various treatments , such as nutritional interventions3 , 6 , pharmacological \n interventions7 , massage8,9,10 , low - intensity exercise10 , ultrasound application11 , or cryotherapy12 . even though some positive effects have been reported\n, \n several studies did not find any reductions in the symptoms of muscle injuries . beside these treatments ,\nstatic or pulsed electromagnetic field therapy have been used for \n the treatment of doms13,14,15 .\nagain , some \n authors reported positive effects on doms symptoms , whereas others were not able to find \n benefits13 , 14 .\napplication of a pulsating electrostatic field ( pesf ) , which is a \n comparable but not identical technique , might be a further method capable of reducing the \n symptoms of muscle soreness .\na pesf was shown to increase vasomotion and as a consequence \n blood flow16 , to reduce the formation of \n rouleaux , and to increase metabolic activity16 , 17 .\nfurthermore , a pesf may function as an \n ion pump able to move calcium ions , the concentration of which was shown to be increased \n after eccentric exercise with detrimental effects2 , \n 18 .\ndue to these effects , it might be \n speculated that a pesf could prevent the development of doms and muscle strength loss after \n muscle damaging exercise .\ntherefore , the aim of the present study was to investigate the \n effect of pesf application on sensation of muscle soreness and muscle strength after \n eccentric exercise .\nnine sport students ( 5 males , 4 females ) without any medical problems and not adapted to \n eccentric exercise were recruited for the study .\nall of them were informed about the study \n aims and gave written informed consent for participation .\ntwo participants ( one male and one \n female ) had to be excluded from the final analysis , one because of a pre - start muscle \n soreness score of already 4 and one because of a pre - start ck value of 333 u / l . therefore , 7 \n participants ( 4 males and 3 females ; weight , height , and age : 74.35.7 kg and 71.05.3 kg , \n 183.09.9 cm and 172.36.4 cm , and 26.52.4 years and 24.31.2 years , respectively ) were \n included in the final analysis .\nthe study was carried out in conformity with the ethical \n standards of the declaration of helsinki and was approved by institutional review board of \n the department of sport science , university of innsbruck .\nthe study was designed as a single - blinded , placebo - controlled cross - over intervention \n study .\nall participants performed 2 downhill running sessions on a treadmill separated by at \n least 4 weeks . before and at different time points after the sessions\n, muscle soreness \n score , creatine kinase ( ck ) , and jump ability were assessed as described in detail below . \n\nthe first running session was carried out in a slightly modified form according to kingsley \n et al5 .\nrunning sessions started with a \n 3 min stage of horizontal running at 5 km / h ( warm - up ) .\nthereafter , the inclination was set \n at 17.5% , and the speed was increased every minute by 1 km / h until reaching approximately \n 70% of the age - predicted maximal heart rate ( hr ) ( calculated as 220 age ) .\noverall , the running duration was 30 \n minutes , not including the warm - up time . during the second test\n, the speed was regulated in \n the same way as during test one but independent of hr in order to have identical test speeds \n and a comparable muscular stimulus . immediately after each run ,\nhalf of the subjects were \n treated in a sitting position with a pesf for 45 min , and half of the subjects were exposed \n to a sham treatment .\nafter at least 4 weeks , in which participants were advised not to \n change their physical activity habits , the subjects that were treated with a pesf during the \n first session received the sham treatment and those that were treated with the sham \n treatment during the first session received the pesf treatment .\nthe ( negative ) pesf was generated with a new health \n 9000 device ( akern srl , pontassieve , italy ) and was applied through a mat with a field \n intensity of 9000 v , a current of < 9 ma , and a pulsatile frequency of 50 hz . the \n electrostatic field was confined to the ion mat surface , and it has been proven to be \n safe17 .\nthe general rating of muscle soreness was assessed as described by trombold et al.3 before and immediately after the runs , \n immediately after the 45 min treatment or sham treatment , and 48 hours after treatment . \n\nparticipants subjectively rated the degree of soreness using a visual analog scale of 0 to \n 10 , with 0 describing no soreness and 10 describing unbearable soreness . jump ability \n ( jump and reach test ) was assessed before running , after the 45 min session , and 48 hours \n after the running .\nck activity was assessed before running and 48 hours after running from \n capillary blood samples with a reflotron sprint device ( reflotron sprint , mannheim , germany ; \n reference range for men : 24195 u / l at a measurement temperature of 37 c ) .\ndelta values ( ) were calculated as post values \n ( at different time points ) minus pre values for both the pesf application and sham setting . \n\ndifferences at baseline , changes in the course of pesf or sham treatment , and differences \n between conditions ( values for the pesf and sham treatment ) were assessed by paired \n student s t - tests or the wilcoxon test as appropriate .\nspearman correlation analyses were \n used to calculate associations between ck and cmj changes and muscle soreness score .\nwhen compared with the pre \n values , the muscle soreness score was increased at all time points and under both conditions \n ( p<0.05 ) .\njump performance was reduced immediately after the sham application ( p=0.038 ) \n and tended to be reduced immediately after the pesf application ( p=0.054 ) . table 1table 1.values for jump height , creatine kinase , and muscle soreness score in the courses \n of the pesf and sham treatmentspreafterrunafter45 min 24 hafter48 hafterjump and reach ( cm)pesf276.28.7273.07.03.33.9273.010.53.33.6sham276.521.6272.023.54.55.3272.023.24.56.2creatine kinase ( u / l)pesf133.632.1171.971.338.358.7sham100.141.0271.7274.5171.6285.8muscle soreness scorepesf1.41.43.61.72.12.04.02.02.61.65.10.93.71.64.61.53.12.0sham1.01.04.01.43.01.74.11.73.12.26.71.75.72.26.42.45.43.2pesf : pulsating electrostatic field . the table represents values of the same \n participants receiving the pesf and sham treatments ( n=7 , crossover design ) . \n \nthere was a trend toward significant differences in delta values ( = \n after values ( i.e. 45 min , 24 h , and 48 h after ) minus pre value ) between treatments \n ( pesf vs. sham ) . shows values for ck , muscle soreness score , and jump height in the courses of \n the pesf and sham treatments .\ntwenty - four and 48 hours after downhill running , the muscle \n soreness score ( mss ) tended to be less after pesf administration when compared with the sham \n treatment ( mss : 3.71.6 vs. 5.72.2 after 24 h and 3.12.0 vs. 5.43.2 after 48 h , \n respectively ; 0.05` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSequential C\u2013O decarboxylative vinylation/C\u2013H arylation of cyclic oxalates via a nickel-catalyzed multicomponent radical cascade\n\nPaper sections:\nIntroduction\nIn the last decade, the nickel-catalyzed cross-coupling reaction has emerged as a powerful technique to construct C-C bonds in chemical synthesis. 1 Notably, nickel-catalyzed multicomponent reactions, that allow for the formation of multiple C-C and/or C-heteroatom bonds thus enabling the streamlined synthesis of complex molecular scaffolds in a single operation, are particularly attractive due to their good compatibility and unique selectivity. 2 Signi\ue103cant progress has been achieved in the area of catalytic multicomponent difunctionalization of unsaturated systems, enabling the simultaneous, one-pot installation of two functionalities over double bonds or triple bonds via nickel catalysis (Fig. 1). 3,4 In contrast, there has been a lack of reports in which saturated hydrocarbons have been manipulated for cross-coupling at more than one reaction site in one single operation. 5 This catalytic strategy would simultaneously install two sp 3 C-C bonds in saturated hydrocarbons, readily available and abundant building blocks in organic synthesis; nevertheless, the realization of such a strategy requires the ability to overcome the relative inertness of saturated hydrocarbons and to control the selectivity in the presence of multiple similar chemical bonds.
Alcohols have been widely employed as salient synthetic building blocks in chemical synthesis. Notable advances have been made in selective functionalization of sp 3 C-H bonds of alcohols through the hydrogen-atom-transfer (HAT) process. 6,7 Moreover, alcohols can function as latent alkylating agents through transition-metal-catalyzed ipso-C-O activation 8 or homolytic C-O cleavage. 4j,k,9,10 These catalytic approaches enable the facile construction of diverse structural motifs from abundant alcohols. Nevertheless, one single transformation that combines ipso-C-O functionalization and remote C-H functionalization of alcohols, which would provide an attractive platform for the synthesis of highly functionalized sp 3 -rich scaffolds, 11 has not been reported yet. We herein report a selective, cascade C-O bond vinylation/C-H bond arylation of alcohols that achieves site-selective dual carbofunctionalization of simple abundant aliphatic alcohols via a photoredox/nickel 12enabled multicomponent radical cascade process. This strategy relies on a synergistic combination of alkyl oxalate decarboxylation, 1,5-hydrogen atom transfer (1,5-HAT) of the vinyl radical, and C(sp 3 )-C(sp 2 ) cross-coupling. Our original design for this radical cascade strategy is outlined in Fig. 1. Speci\ue103cally, we envisioned that a radical addition of alkylalkyne would give rise to a s-type vinyl radical I, which would prefer to undergo an intramolecular 1,5-HAT process to yield a nucleophilic alkyl radical species II. 13 Subsequent nickel-mediated coupling of alkyl radial II with aryl halides would forge a C(sp 3 )-Ar bond, 12 and \ue103nally lead to a sequential two-site functionalization of oxalates, i.e. C-O decarboxylative vinylation & C-H arylation (Fig. 1). We are particularly interested in exploring cyclic alkyl oxalates to construct highly functionalized cycloalkanes, 14 due to two considerations: (i) this synergistic cascade process would undoubtedly expedite the synthesis of challenging aliphatic rings, and more importantly, would provide a novel retrosynthetic disconnection for complex saturated ring systems from simple starting materials; (ii) conformation of cyclic substrates might be bene\ue103cial for the intramolecular 1,5-HAT migration of vinyl radical species. 15
\n\nResults and discussion\nWe began our investigations by employing tertiary cyclic oxalate 1 as a model substrate to test the possibilities (Table 1).
Pleasingly, we found that irradiation of a DMSO solution of 1, aliphatic alkyne 2, and 4-bromobenzonitrile 3 did afford the desired 1,3-vinylarylation product 4 in 84% yield in the presence of catalytic Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 , NiCl 2 (Py) 4 , 4,4 0 -di-tertbutyl-2,2 0 -dipyridyl (dtbbpy), and bis(4-methoxyphenyl) methanone (Table 1, entry 1). The countercation of oxalates impacted the reaction efficiency to a small extent, while the use of cesium oxalates afforded higher yields than the corresponding Li, Na, K salts (entries 2-4). Further evaluation indicated that both Ni(II) and Ni(0) catalysts were able to promote the desired transformation, with the precatalyst NiCl 2 (Py) 4 proving optimal (entries 5-9). Control experiments demonstrated that the photocatalyst, the nickel catalyst, and visible light were all essential to this synergistic cascade process, as the desired 1,3-vinylarylation products were not observed in the absence of any of these components (entries 10-12). Nevertheless, low conversion (27% yield) was still observed in the absence of the bipyridine ligand (entry 13). The use of bis (4methoxyphenyl)methanone as an additive proved to be slightly bene\ue103cial to the reaction efficiency (entry 14). 13 With the optimal conditions in hand, we next turned our attention to evaluating the applicability of substrates as well as the potential limitations of this dual functionalization protocol. As shown in Scheme 1, a number of tertiary cyclic oxalates, readily prepared from the corresponding alcohols, could undergo the sequential C-O vinylation/C-H arylation with excellent site-selectivity, installing both vinyl and aryl functionalities onto the skeletons of alcohols under redox-neutral and mild conditions (products 4-14, 36-77% yields). A number of substituents including alkyl, ketal, ketone, and alkene on the cyclohexyl alcohols were tolerated in this dual catalytic cascade system, furnishing multi-substituted cyclic alkanes in a single operation under mild conditions (products 5-9, 36-77% yields). Nonetheless, steric hindrance of the substituents was found to have a considerable effect on the reaction efficiency: installing a methyl group at the aor gposition, or replacing methyl with ethyl at the ipso position of cyclohexyl oxalates resulted in decreased efficiency (products 6-8, 36-54% yields). Pleasingly, saturated O-, S-, and Nheterocyclic oxalates turned out to be viable substrates, yielding the vinyl/aryl-disubstituted saturated heterocycles with good efficiency (products 10-13, 50-76% yields). Moreover, cyclopentyl oxalates were also competent substrates, delivering the 1,3-difunctionalized cyclopentane products in synthetically useful yields (product 14, 40% yield).
Unfortunately, cyclic oxalates with larger or smaller ring sizes (e.g. 4-and 7-membered cyclic oxalates), bicyclic oxalates, and linear oxalates were unsuccessful substrates for this cascade protocol, probably due to the less favorable conformation (for unsuccessful oxalates, see Section 5, page S62 in the ESI \u2020). Interestingly, the reaction of 4-methylenecyclohexyl oxalate with aryl bromides under optimal conditions afforded the 1,5-vinylarylation products in moderate yields (products 15-18, 58-64% yields). Excellent chemoselectivity was observed in this case, with no observations of 1,3-difunctionalized products. We reasoned that allyl-Ni species, generated via intramolecular 1,5-HAT followed by nickel trapping, underwent a selective coupling with aryl bromide at the terminal position, probably due to steric hindrance, to afford the cyclohexene product. This protocol represents a new and efficient platform to construct highly functionalized saturated heterocycles, important structural scaffolds for bioactive molecules, from simple starting materials. Next, we examined the scope with respect to the alkyne component (Scheme 1). Pleasingly, a wide range of terminal alkylalkynes could be efficiently employed in this cascade protocol, yielding the corresponding trans-alkenes in moderate to good yields (products 19-29, 45-74% yields). Notably, aliphatic alkynes tethered with complex molecules, exempli\ue103ed by oxaprozin and dehydroabietic acid, also worked with moderate efficiency, further demonstrating the amenability of this synergistic strategy for late-stage manipulations (products 27 and 29, 53% and 50% yield, respectively). Nevertheless, internal alkynes proved to be inefficient substrates, most of which remained intact under the standard conditions.
Finally, we explored the scope of aryl halides in this multicomponent transformation (Scheme 1). Aryl bromides containing electron-withdrawing substituents, including aldehydes, ketones, esters, nitriles, sulfones, and tri-\ue104uoromethylates, are competent coupling partners under optimal conditions, delivering the desired products with good efficiency (products 30-35, 53-70% yields). The mild conditions allow for the good tolerance of these important functionalities. This reaction is amenable to heteroaryl halides, selectively installing pyridines and benzothiazoles into cyclohexanes with moderate yields (products 36-38 and 41-42, 50-77% yields). Additionally, (hetero)aryl iodides/chlorides also participated in this sequential C-O/C-H dual functionalization process smoothly (products 39-42, 52-61% yields). Electron-rich aryl halides were applicable coupling partners, albeit with decreased efficiency (products 39-40).
To further demonstrate the synthetic application of our cascade protocol, we have performed several transformations by utilizing the alkene functionality (Scheme 2). The double bond of compound 41 readily underwent selective hydrogenation with H 2 in the presence of a Pd/C catalyst (product 43). Epoxidation of compound 30 with m-CPBA gave epoxide 44 in 65% yield. Furthermore, ozonolysis of 30 led to the formation of aldehyde 45, which could subsequently be oxidized to the corresponding carboxylic acid 46, or be reduced to the related alcohol 47 in good yield.
To shed some light on the potential reaction pathway, we have conducted several mechanistic experiments (Scheme 3). Reaction of ethynylcyclopropane with oxalate 1 and aryl bromide 3 gave the allene product 48, presumably generated via a ring-opening/cross-coupling process, indicating the involvement of vinyl radical species (Scheme 3A). Initially, we assumed that the 1,5-HAT process could be related to the subtle conformation of oxalates. We also found that the expected 1,5-HAT process is reliant on the nature of the vinyl radicals (s-type vs. ptype). For instance, competitive experiments between aryl and aliphatic alkynes showed that arylalkynes exhibited higher reactivity to afford the exclusive formation of 1,2-alkylarylation products, 4j and the 1,5-HAT/coupling product was not observed in this case (Scheme 3B). Regarding the coupling step, we prepared the ligated Ar-Ni(II) complex 50, 16 and found that the stoichiometric reaction of the Ar-Ni(II) complex with alkyne and oxalate didn't form the desired 1,3-disubstituted cycloalkane product 51, suggesting that Ar-Ni(II) might not be a reactive intermediate for this cascade transformation (Scheme 3C). Nevertheless, the Ar-Ni(II) complex was able to catalyze the synergistic cascade reaction, giving the 1,3-disubstituted cyclohexane 33 in 30% yield in acetone (Scheme 3D).
On the basis of these experimental results as well as literature precedents, 12,17 a plausible mechanism for this photoredox/ nickel-catalyzed dual functionalization is depicted in Scheme 4. A thermodynamically feasible SET event between the photoexcited Ir-catalyst B and oxalate C would generate a tertiary alkyl radical D via decarboxylation, followed by a radical addition of alkyne to give rise to a s-type vinyl radical E. The resulting vinyl radical E would go through an intramolecular 1,5-HAT to selectively activate the sp 3 C-H of oxalates and to afford a nucleophilic, secondary alkyl radical species G. Subsequent interception of alkyl radical G by Ni(0) H would generate an alkyl-Ni(I) species I, which then undergoes an oxidative addition with aryl halide J to yield an (alkyl)(aryl)Ni(III) intermediate K. 17 This high-valent Ni(III) complex K would undergo a feasible reductive elimination to forge the C(sp 3 )-Ar bond and furnish the \ue103nal product L as well as Ni(I) species M. Finally, a SET event between Ni(I) M and the reduced Ir(II) F would regenerate Ni(0) H and the ground state Ir(III) A to close these two catalytic cycles. At this stage, we could not preclude another pathway that proceeds via oxidative addition of aryl bromide to Ni(0) followed by interception of Ar-Ni(II) N by alkyl radical species to afford the same (alkyl)(aryl)Ni(III) K.
\n\nConclusions\nIn summary, we have developed a sequential C-O decarboxylative vinylation/C-H arylation of cyclic oxalates via photoredox/nickel dual catalysis. This synergistic protocol enables efficient and selective assembly of both vinyl and aryl functionalities onto saturated cyclic hydrocarbons in one single operation under mild and redox-neutral conditions, providing a new and complementary retrosynthetic method for densely functionalized saturated cyclic hydrocarbons. The mild conditions allow for excellent compatibility of functional groups and substrate scope in the oxalates, alkynes, and (hetero)aryl halides.
\n\nConflicts of interest\nThere are no con\ue104icts to declare.
", "answer": "A selective, sequential C-O decarboxylative vinylation/C-H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis is described. This protocol utilizes a multicomponent radical cascade process, i.e. decarboxylative vinylation/1,5-HAT/aryl cross-coupling, to achieve efficient, site-selective dual-functionalization of saturated cyclic hydrocarbons in one single operation. This synergistic protocol provides straightforward access to sp 3 -enriched scaffolds and an alternative retrosynthetic disconnection to diversely functionalized saturated ring systems from the simple starting materials.", "id": 497} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSingle point activation of pyridines enables reductive hydroxymethylation\u2020\n\nPaper sections:\nIntroduction\nNitrogen-containing heterocycles play an essential role in organic chemistry. They are found in a wide range of pharmaceuticals, drug candidates, agrochemicals, natural products, functional materials, and catalysts.1 Despite considerable synthetic advances, the pharmaceutical industry still requires processes that allow the facile preparation of aliphatic nitrogen-containing heterocycles along with methods that install small but essential functional groups such as \u2013CH2OH and methods which enable the rapid and robust preparation of such useful molecules are of great interest to the synthetic chemistry community (Scheme 1).2
Dearomatisation reactions have garnered considerable interest because they represent an expedient way to prepare complex three-dimensional molecular scaffolds from flat and readily available aromatic compounds.3 Given the particular relevance of piperidines, and the commercial availability of pyridines, the dearomative pathway represents an attractive approach to preparing saturated azacycles.4 In particular dearomative methods that form both C\u2013H and C\u2013C bonds represent an important class of reaction that are particularly versatile and efficient. However, despite their importance,5\u201312 these types of reactions continue to be underrepresented in the literature.
Recently our own laboratory has reported a new iridium-catalysed interrupted transfer hydrogenation process that leads to the reductive hydroxymethylation of pyridines.13\u201316 In addition to forming two new C\u2013H bonds, this process also forms a new C\u2013C bond in a single synthetic step. Mechanistic work has shown that the metal catalyst oxidises formaldehyde in methanol to methyl formate, forming a metal hydride in the process.13 Addition of the metal hydride to the C-2 position of the pyridine then forms a key enamine intermediate A. Reaction of the enamine with excess formaldehyde, and subsequent iminium ion reduction then completes the transformation.
As with many dearomative reactions, it is necessary to activate the pyridine substrates to facilitate the initial aromaticity-breaking step. We found that activation could be achieved through a two-point strategy: (i) quaternisation of the pyridine nitrogen to form a highly electron deficient pyridinium salt and (ii) the presence of an electron-withdrawing substituent in the 4-position of the pyridine to further enhance the electron deficiency. The 4-substituent also ensures the initial reduction happens at C-2 exclusively, and prevents over reduction in situ.
While our initial work reported 3-hydroxymethylation of pyridines, the requirement of a strongly electron withdrawing group in the 4-position is a significant limitation. Groups such as esters and ketones work well, however any less electron-withdrawing substituents result in either low yielding or completely inactive pyridines. For example 4-phenylpyridine was poorly active under the reaction conditions (giving product 2a in 15% yield using an iridium catalyst and 27% yield using a rhodium catalyst, Scheme 2) and pyridines with alkyl and heteroatom substituents were completely inactive. 4-Aryl substituents are of particular interest as this motif can be found in molecules such as the anti-depressant drug Paroxetine (Scheme 1).
\n\nResults and discussion\nIn order to address this limitation, we set about developing a single point activation strategy that would enable the use of more electron-rich pyridines, such as 4-phenyl pyridine. From analysis of crude reaction mixtures, it was apparent that the initial dearomative addition of a metal hydride to the pyridine C-2 position was the troublesome step when using less electron-poor substrates. Therefore, our first approach was to utilise metals which have a stronger reductive profile while using N-benzyl-4-phenylpyridinium iodide 1a as a test substrate (Scheme 2).17 In this case, both rhodium (27%) and ruthenium (17%) were found to give higher yields of 2a than iridium (15%).
To further increase the electron deficiency of the heteroaromatic system, while maintaining a single point of activation (i.e. quaternisation), analogous substrates bearing electron-deficient benzyl groups were then prepared and subjected to the metal-catalysed conditions. Using [Ru(p-cymene)Cl2]2 as the pre-catalyst, pleasingly the 2-nitrobenzyl substrate 1b was found to give the product 2b in a higher 40% yield, as did the 2,4-bistrifluoromethyl substrates 1c (2c, 65%) and 3,5-bistrifluoromethyl substrates 1d (2d, 32%). [IrCp*Cl2]2 was found to generate a far less proficient catalytic species, delivering 2c in only 25% yield. Finally, [RhCp*Cl2]2 was also found to deliver 2c in a good yield (65%). After deciding that the 2,4-bistrifluoromethyl activating group gave the best yield, substrate 1c was taken as a model substrate and subjected to further optimisation and screening (Table 1). Ru catalysis was studied further because it is significantly less expensive than Rh.
\n\n\n1H NMR yield using trimethoxybenzene as internal standard.
Using [Ru(p-cymene)I2]2 as catalyst.
Using the bromide salt of 1c.
Isolated yield.
\n\nResults and discussion\nInitially, the role of KI additive, thought to improve the reducing ability of the metal hydride, was investigated; relative to our initial conditions using 4 equivalents,18,19 the absence of any KI (40%) or the presence of 2 equivalents (60%) led to a reduced yield of 2c (entry 2 and 3). However, increasing KI loading to 6 equivalents (50%) also led to a decrease in yield (entry 5). Using the bromide salt of 1c as starting material, instead of the iodide salt, also led to a slight decrease in yield (61%, entry 6).
Changing the base to potassium methoxide resulted in a drop in yield to 24%. Decreasing the loading of magnesium methoxide to 0.5 equivalents had a limited effect (64%) but increasing the loading to 1 equivalent increased the yield to 70%; a further increase of base equivalents did not increase the yield (entry 8, 9 and 10). Finally, decreasing the paraformaldehyde equivalents to 10 led to a reduction in yield (65%) while increasing to 30 equivalents increased the yield to 72%, giving an isolated yield of 69% (entries 11 and 12). Note that it was necessary to add excess formaldehyde in order to ensure complete reaction of the enamine formed in situ. Although the optimised conditions differ from our initial iridium catalysed work, we believe that mechanistically the reaction process proceeds in a similar fashion (see ESI\u2020).13 With the optimal N-activating group and conditions in hand, a range of 4-aryl substituted pyridinium salts were subjected to the reaction conditions (Scheme 3).
The starting materials were prepared in one step from 2,4-bistrifluoromethylbenzyl iodide and the corresponding pyridine. While the model 4-phenylpyridine 1c gave the product 2c in 69% yield, scaling this reaction to 3 mmol, led to the formation of 2c in an increased yield of 73%. Pleasingly we found that a number of both electron-donating (methyl, tert-butyl, and methoxy) and electron-withdrawing (trifluoromethyl, fluoro, chloro, methyl ester, and sulfone) substituents were well tolerated on the C-4 aromatic group, giving the products in a range of yields (39\u201378%). Within the C-4 aromatic group, substitution was tolerated at the ortho, meta, and para positions, together with 3,5-disubstitution and 3,4,5-trisubstitution. Of note, substrate 2j bearing a 4-fluorophenyl group was formed in 78% yield and was used as the key step in the synthesis of (\u00b1)-Paroxetine, vide infra. In addition, substitution at the 3-position of the pyridine is also tolerated (2r\u20132u), giving the hydroxymethylated product in reasonable yields (37\u201355%). In this position aromatic groups bearing ortho, meta, and para substitution along with a n-butyl group were all shown to be viable substrates. The activation strategy utilising the 2,4-bistrifluoromethylbenyl group was then extended to enable the use of pyridines substituted at the 4-position with strongly electron-rich heterocycles. These substrates are completely inactive when using the standard N-benzyl activating strategy which shows the importance of the electron withdrawing N-benzyl derivative described here. Carbazole (2x 52%), indole (2w, 67%), and benzofuran (2v, 49%) C-4 substituents were all used successfully to give the hydroxymethylated products in good yields. These results highlight the ability of this methodology to selectively activate and functionalise pyridines in the presence of other heteroaromatic rings. Furthermore, the N-2,4-bistrifluorobenzyl salt of Rosoxacin ester, a commercially available quinoline antibiotic, was subjected to the reaction conditions and the desired product 2y was isolated in 23% yield, showing that late stage derivatisation of important pharmaceutically relevant molecules can be achieved with this methodology. Moreover, the highly electron-rich 4-methoxypyridine was successfully activated using our strategy to give enol ether 2z in 50% yield. While the corresponding 4-alkyl products 2aa and 2ab, bearing a methyl and tert-butyl group respectively, were also formed, the isolated yields were only 20% and 27% respectively. However, despite these lower yields, they do demonstrate a proof of concept that simple C-4 alkyl-substituted pyridines can now be utilised in this methodology for the first time. Unfortunately substrates lacking a 4-substituent did not undergo hydroxymethylation successfully and gave complex mixtures of products (2ac); we plan to tackle this issue in our future work.
To highlight the versatility of the products, further synthetic transformations were undertaken on a representative example 2c (Scheme 4). The newly installed CH2OH group was converted to the corresponding alkyl iodide 4via an Appel reaction in good yield (66%). Importantly, removal of the activating group was achieved easily through protection of the free \u2013OH group with a benzyl group followed by either treatment with 1-chloroethyl chloroformate and subsequent reaction of the intermediate carbamate with methanol to furnish the free amine 5 in 56% yield over two steps. Alternatively treatment with methyl chloroformate, allowed a protecting group switch to form carbamate 6 in good yield (66%) over two steps. A Mitsunobu reaction of 2c using sesamol, followed by cleavage of the activating group delivered the corresponding amine 7 in 43% yield over two steps. These synthetic manipulations, together with the easy removal of the benzyl derived activating group, enables the wide array of products to be converted into highly useful small molecules.
In order to show the utility of this methodology, we chose to prepare Paroxetine, which is a selective serotonin reuptake inhibitor used as a pharmaceutical drug to treat a variety of conditions.20 Starting with commercially available 4-bromopyridine hydrochloride we prepared (\u00b1)-Paroxetine using our methodology in only six steps and 20% yield (Scheme 4). Following the preparation of 2j, three simple and efficient transformations gave Paroxetine. The first of these was a key substrate controlled hydrogenation using Crabtree's catalyst to deliver the piperidine 8 (3\u2009:\u20091 dr, from which the pure trans isomer of 8 was isolated in 65% yield). Finally, the synthesis was completed with a Mitsunobu reaction to install the electron rich aryl group (84%) and removal of the activating group using ACE-Cl and methanol (55%). In order to probe the mechanism of the reaction we have subjected 1j to the reaction using [CD2O]n and observed deuterium incorporation on C-2, C-6 and the exocyclic hydroxymethyl group. This was consistent with our proposed mechanism and also provided a convenient method to access deuterated Paroxetine if so desired (see ESI pp56\u2020).
\n\nConclusions\nIn conclusion, we have developed a new catalytic system and shifted the boundaries of the dearomative hydroxymethylation reaction, expanding the scope far beyond what was possible in our initial work. Ranging from 4-arylpyridines to the electron-rich 4-methoxypyridine the hydroxymethylation proceeded in good yields. The key aspect of the work involves the use of a ruthenium catalyst in conjunction with a highly electron-deficient 2,4-bistrifluoromethylbenzyl activating group. This bespoke activating group can be readily removed to furnish the free amine. Finally, we have utilised this highly useful methodology in the synthesis of (\u00b1)-Paroxetine and plan to employ it further to make more medicinally relevant molecules and natural products.
\n\nConflicts of interest\nThere are no conflicts of interest.
", "answer": "The single point activation of pyridines, using an electron-deficient benzyl group, facilitates the ruthenium-catalysed dearomative functionalisation of a range of electronically diverse pyridine derivatives. This transformation delivers hydroxymethylated piperidines in good yields, allowing rapid access to medicinally relevant small heterocycles. A noteworthy feature of this work is that paraformaldehyde acts as both a hydride donor and an electrophile in the reaction, enabling the use of cheap and readily available feedstock chemicals. Removal of the activating group can be achieved readily, furnishing the free NH compound in only 2 steps. The synthetic utility of the method was illustrated with a synthesis of (\u00b1)-Paroxetine.", "id": 498} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is well known that genes can be silenced by antisense rna oligonucleotides called small interfering rna ( sirna ) ( 1,2 ) . in order to design an efficient sirna sequence , empirical rules based on the features of the sirna sequence\nhave been discovered , including , for example , low g / c content , lack of self - structure , preference of a at position 3 , absence of g or c at position 19 and asymmetry in the stability of the terminal base pairs ( 310 ) .\nthe self - structure of the target and oligonucleotide is also an important consideration for the effective binding ( 1115 ) .\nit is desirable to select an oligonucleotide having high accessibility to the target - binding site and low duplex stability . here\n, the oligowalk server , which predicts efficient sirna sequences using an accessibility calculation with a convenient web interface , is described .\noverall , the positive predictive value of the server is 0.786 , meaning that 78.6% of the sirnas selected by the server will be efficient at silencing ( 16 ) .\nthe positive predictive value was determined by testing against a database of sirna experiments conducted under diverse experimental conditions ( 17 ) . in the calculation of the oligowalk server ,\nunimolecular and bimolecular self - structures for the sirna are considered along with unimolecular self - structure in the target at the oligonucleotide binding region ( 16 ) .\noligowalk predicts the free energy changes ( g ) involved in these equilibrium states ( 18 ) .\nthe predicted thermodynamics ( g ) , plus the oligonucleotide sequence features ( 19 ) , are then utilized to predict sirna efficacy for candidate sirna sequences ( 16 ) , which are generally 19 nucleotide duplexes with 3 dinucleotide dangling ends ( 7 ) .\na support vector machine ( svm ) program ( 20 ) is embedded in the server to take the thermodynamic and sequence features as input .\nthe svm classification model used in the server has been proven to be able to predict efficient sirna ( greater than 70% inhibition of the target mrna expression ) with high accuracy ( 16 ) .\nthe svm was trained on a sirna database that contains 2431 experimental results conducted in human cells at 37c ( 10 ) .\nthe output of the oligowalk server is a table of sirna candidates , showing the sirna sequences and the probabilities of being efficient ( having silencing efficacy larger than 70% ) .\neach of the free energy change terms for each candidate is also listed in a separate table .\nthe oligowalk server uses the cgi ( common gateway interface ) module of perl for taking user input and submitting calculations from the homepage .\nthe input of oligowalk server is the rna sequence of the target gene . only a , u , t , g and c are the acceptable types of nucleotides in the sequence ( the server will replace the nucleotide t with u for calculations ) , and the maximum sequence length is 10 000 nucleotides .\nan email address is required because the server sends an email to the user when the calculation is completed .\nsubmit query , the server generates a list of efficient sirna candidates for the target gene .\njobs are submitted by the server to a cluster of seven nodes with 3.2 or 3.4 ghz pentium 4 processors running fedora linux ( http://fedoraproject.org/ ) , managed by sun grid engine ( http://gridengine.sunsource.net/ ) .\nwhen the calculation is complete , an html ( hypertext markup language ) page is generated with links to tables containing predicted sirna efficacy data and thermodynamic binding data . in the sirna efficacy table ( figure 1 ) , the sequences of sirna candidates are ranked in the output list by their probabilities of being efficient sirna .\nthe probabilities are predicted by a svm embedded in the web server for selecting efficient sirna .\nthe classification model ( 16 ) used in the svm was trained with a publically available database ( 10 ) , using thermodynamic and sequence features of sirna candidates . the position number of each sirna candidate is also listed in the table as the index of the 5 most base in the target - binding region . \n\nthe sequences of sirna are ranked from top to end by their probabilities of being efficient ( antisense efficacy larger than 70% ) . a table of sirna candidates generated by oligowalk server .\nthe sequences of sirna are ranked from top to end by their probabilities of being efficient ( antisense efficacy larger than 70% ) .\nin addition , the predicted equilibrium thermodynamics table is generated as a reference for advanced users . in the table\n overall ( in kcal / mol ) is the overall free energy change of oligonucleotide - target binding , when all contributions are considered , including breaking target and oligonucleotide self - structures ( 18 ) .\n duplex ( in kcal / mol ) is the free energy change of hybridized duplex between oligonucleotide and target ( antisense sense duplex ) , .\nthe value is independent of oligonucleotide concentration because it is a standard free energy change . \ntm - dup ( in c ) is the melting temperature in degrees for the duplex formation of oligonucleotide and target . \nbreak - targ. ( in kcal / mol ) is the free energy cost to open the intramolecular target base pairs for oligonucleotide binding , .\na more negative number indicates higher free energy cost , which is unfavorable for oligonucleotide - target binding . \nintraoligo ( in kcal / mol ) is the free energy change of intramolecular oligonucleotide structure , .\nit usually has a negative value or , if there is no favor - able intramolecular structure , it is zero . \ninteroligo ( in kcal / mol ) is the free energy change of intermolecular oligonucleotide structure , .\nantisense bimolecular structure , which decreases the oligonucleotide - target ( antisense sense ) binding affinity . end_diff. ( in kcal / mol ) is the free energy difference between the 5 and 3 end of the antisense strand of sirna , with windows of two base pairs .\nfunctional sirna prefer to have an unstable 5 end ( 3 ) , which means a positive end_diff .\n prefilter_score is the score calculated with a method based on the empirical rules by reynolds et al . ( 7 ) .\n( 7 ) , except for the melting temperature of intramolecular oligonucleotide self - structure because the free energy ( 21 ) and enthalpy parameters ( 22 ) used by oligowalk are more recent .\nwhen calculating the prefilter score , 57c is used as the cutoff of the intramolecular oligonucleotide melting temperature , as suggested in another study ( 23 ) . as an example\n, the prediction of the webserver is compared with experimental results in figure 2 . in the experiment ( 3 ) , sirna were tested for efficacy against the target mrna , human cyclophilin ( genbank i d : m60857 ) , at 37c .\nthe inhibition efficacy of each sirna is defined as 100% minus the percentage of mrna level after sirna application as compared to matched control .\nthe prediction result is the probability of being efficient ( having inhibition efficacy larger than 70% ) , which is calculated with the server . in figure 2 , most of the sirna with high inhibition efficacy are predicted to have high probability of being efficient . \n\nfigure 2.a comparison between the prediction and experimental result . in blue is the experimental result ( inhibition efficacy ) for an mrna target , human cyclophilin ( genbank i d : m60857 ) , at 37c ( 3 ) .\nthe inhibition efficacy is defined as 100% minus the percent level of mrna expression after sirna application as compared to a control . in red\nis the probability ( ranging from 01 ) of being efficient ( having inhibition efficacy larger than 70% ) , as predicted by oligowalk .\na comparison between the prediction and experimental result . in blue is the experimental result ( inhibition efficacy ) for an mrna target , human cyclophilin ( genbank i d : m60857 ) , at 37c ( 3 ) .\nthe inhibition efficacy is defined as 100% minus the percent level of mrna expression after sirna application as compared to a control . in red\nis the probability ( ranging from 01 ) of being efficient ( having inhibition efficacy larger than 70% ) , as predicted by oligowalk .\nadvanced options ( figure 3 ) are available for users who understand the underlying calculations and would like to test novel hypotheses . the option form is written in html , embedded with javascript controlling the options so that they are context - aware .\nthe oligonucleotide concentration does not affect the result of sirna sequence design , because the inputs to the svm are standard free energy changes , g . concentration changes do , however , alter the overall free energy change ( ) , which is provided to the user with the thermodynamic details table .\nthe sense antisense duplex free energy changes are calculated without considering the self - structures of the target . this mode is not recommended for an accurate sirna prediction .\nit is more rigorous to consider the accessibility of the target and oligonucleotide self - structures because binding affinity is lost to open existing base pairs in the target and oligonucleotide .\nthe second mode is to break local structure . in this case , the structure of target is fixed and only the base pairs on the binding site will be broken without refolding the global structure of target . the final and most rigorous mode is to refold the target rna . in this mode ,\nthe rna target is folded before oligonucleotide binding and refolded afterwards for each possible oligonucleotide to consider complete equilibration .\nthe default setting of sirna design is shown in the figure . if the target rna secondary structure is considered , three different prediction methods are available to calculate the free energy change of target self - structure .\nthe first method is optimal structure prediction , where only the optimal structure ( lowest free energy structure ) of the target is considered to calculate the free energy cost of opening the base pairs of binding region .\nthe second method considers a set of suboptimal structures to determine the free energy cost .\neach structure 's free energy cost is weighted according to the free energy change of the structure to arrive at the ensemble cost .\nfor this option , at most 1000 suboptimal structures ( within 10% free energy difference from the optimal structure ) are generated with a heuristic method ( 24 ) .\nthe number of suboptimal structures will be listed in the output table if the target is folded with suboptimal structure prediction method .\nconstrained target structure is the refolded structure where the binding region is forced to be single - stranded , so that the oligonucleotide can bind to it .\nthis is the most rigorous method because it considers every possible secondary structure in the folding ensemble , with boltzmann weight .\nthe structure prediction only folds a certain total number ( folding size ) of nucleotides centered at the binding region .\nthe user can define this number , but the largest folding size is 1000 nucleotides for the webserver in order to save compute time .\nusers can define longer folding sizes by downloading and installing the oligowalk program to a local machine .\n( 7 ) can be used to rule out nonefficient sirna candidates before folding the target sequence , i.e. the sirna sequences having score less than six points will not be considered for the folding step .\nit is suggested to turn on the prefilter option to save considerable computation time ( table 1 ) .\nfurthermore , the scan region can be redefined if the user is interested only in a specific region of the target . \n\ntable 1.calculation size and time of oligowalk server for different target sequencestarget mrna ( genbank id)sequence length ( nucleotide)time ( h : min : sec)memory ( mb)nm_0205487300:57:1793m608578513:55:53110nm_00287012116:09:25112nm_00246721896:36:42113aj27221234606:53:05117the benchmarks were performed with the default options : the oligonucleotide was a 19 base rna ; the folding size of the target was 800 nucleotides centering on the binding site ( full length if the whole target has less than 800 nt ) ; the partition function calculation was conducted ; the entire mrna was scanned ; and the prefilter was on . the time cost changes little for long sequence because the prefilter ( 7 ) is on and number of candidates being folded is limited to about the same number for each sequence.the calculations were submitted and benchmarked on the oligowalk web server ( http://rna.urmc.rochester.edu/servers/oligowalk ) .\neach node has a 3.2 or 3.4 ghz pentium 4 processor running fedora linux.the calculation for sequences less than 800 nucleotides is relatively fast because the dynamic programming arrays are reused for calculations of short sequences ( 16 ) .\ncalculation size and time of oligowalk server for different target sequences the benchmarks were performed with the default options : the oligonucleotide was a 19 base rna ; the folding size of the target was 800 nucleotides centering on the binding site ( full length if the whole target has less than 800 nt ) ; the partition function calculation was conducted ; the entire mrna was scanned ; and the prefilter was on .\nthe time cost changes little for long sequence because the prefilter ( 7 ) is on and number of candidates being folded is limited to about the same number for each sequence .\nthe calculation for sequences less than 800 nucleotides is relatively fast because the dynamic programming arrays are reused for calculations of short sequences ( 16 ) .\nthe oligowalk web server predicts the hybridization thermodynamics of an oligonucleotide binding to a complementary target rna using the most recent rna folding parameters ( 21 , 22 ) .\nit predicts efficient sirna with high accuracy using a transparent implementation of an svm ( 16 ) , which considers both sequence and thermodynamic features .\nthe calculation time and memory size of oligowalk are shown in table 1 for a sample of mrna sequences .\nthe prefilter ( 7 ) that uses local sequence information to narrow down the list of sirna candidates before calculating the equilibrium affinity is used by default .\nfor example , the server takes 3 h and 43 min for a complete scan of all possible sirnas on an mrna having 730 nucleotides using the partition function calculation . for the same sequence ,\nthe algorithm time scales o(mn ) and the memory use scales o(n ) ( table 1 ) , m is the number of candidates and n is the value of folding size .\nthe time and memory costs change little with sequence because the same folding size ( e.g. 800 nucleotides ) is used and the prefilter ( 7 ) is turned on , which limits the number of candidates to be folded in a way that is apparently independent of target length .\nthere is currently significant interest in using sirna for both basic science and medical research .\nthe fact that not all sirna duplexes will function in silencing means that there is a significant cost in trial and error for sirna design .", "answer": "given an mrna sequence as input , the oligowalk web server generates a list of small interfering rna ( sirna ) candidate sequences , ranked by the probability of being efficient sirna ( silencing efficacy greater than 70% ) . \n to accomplish this , the server predicts the free energy changes of the hybridization of an sirna to a target mrna , considering both sirna and mrna self - structure . \n the free energy changes of the structures are rigorously calculated using a partition function calculation . by changing advanced options , the free energy changes \n can also be calculated using less rigorous lowest free energy structure or suboptimal structure prediction methods for the purpose of comparison . \n considering the predicted free energy changes and local sirna sequence features , the server selects efficient sirna with high accuracy using a support vector machine . \n on average , the fraction of efficient sirnas selected by the server that will be efficient at silencing is 78.6% . \n the oligowalk web server is freely accessible through internet at http://rna.urmc.rochester.edu/servers/oligowalk .", "id": 499} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncraniopharyngioma is an uncommon tumor of the nervous system ; it is well - known to recur even several years after surgery .\nwe are here with reporting a case of craniopharyngioma which recurred at a site removed from the original site 5 years after surgery and radiotherapy .\na 4-year - old girl was admitted for progressive deterioration of vision of 2 months duration . in addition\nthere was no history of endocrinopathy , fits or any symptom of raised intracranial pressure . on examination ,\nvisual acuity was questionable perception of light on the right side and counting fingers at 3 m distance on the left .\nimaging revealed a solid and cystic craniopharyngioma in the sellar - suprasellar region [ figure 1a and b ] .\nshe underwent a right frontotemporal craniotomy and transsylvian exploration and almost total excision of the tumor .\npostoperative mr showed a tiny residual tumor adherent to the pons [ figure 2a and b ] .\n( a and b ) showing the preoperative images ( before first surgery ) ( a and b ) images after first surgery showing no residual tumour in the primary site but a small fragment adherent to the pons she was given a course of radiotherapy for this residue 54 gy in 30 fractions .\nfollow - up imaging at the end of 2 years did not reveal any residual tumor [ figure 3 ] .\ntwo years after surgery and radiotherapy no recurrence imaging was being done periodically to check for recurrence .\nthe 5-year surveillance imaging showed a recurrence in the right sylvian fissure along the route taken during the first surgery .\nthere was no evidence of tumor in the sellar - suprasellar area [ figure 4a and b ] .\nshe underwent reexploration by the same route , and a tiny fragment densely adherent to the middle cerebral artery was left behind .\n( a and b ) showing remote recurrence five years after first surgery and radiotherapy .\nalthough craniopharyngiomas are benign tumors they are known to recur even after years and even after the administration of radiotherapy , recurrence rates ranging from 25% to 70% .\nrecurrences at a site removed from the original site are very rare < 25 cases have been reported .\nthese ectopic recurrences are not to be misinterpreted as ectopic primary occurrences since craniopharyngioma can occur anywhere along the obliterated rathke 's pouch\n. these ectopic recurrences may occur along the surgical pathway or at a site , not along the surgical pathway .\nthe cells of the tumor may get implanted and may subsequently metamorphose into a fresh neoplasm .\nthese tumor cells may in turn give rise to the regrowth of the tumor . the usual time to recurrence is around 4 years . but why this has to be a peculiarity of craniopharyngiomas can not be explained . another way the tumor may get seeded at a distant site\nthe evidence for this is strong since tumor cells have been observed in the csf .\nalthough most recurrences are along the surgical corridor an instance where the recurrence has occurred in the spine has been recorded .\nwhen the transsphenoidal route is used , the csf spaces are not violated this may explain the absence of recurrences after transsphenoidal route .\nit is not surprising to observe that the histologic examination of the primary and recurrent lesions are the same .\nrecurrences rates are said to be low after total surgical excision . but recurrences even decades after a quiescent period are well - known .\nit can be assumed that radiotherapy would have sterilized the surgical corridor and ectopic recurrences will not occur .\nbut this was not the case in our patient , and in the few that have been reported .\ntotal excision is not an assurance that recurrences at ectopic or primary site will not occur .\ncertain measures have been proposed to minimize these ectopic recurrences , protecting the operative field with patties to prevent seeding , emptying the cyst prior to removal of tumor , thorough irrigation of the field before dural closure .\nprobably , a higher mib-1 index and expression of p53 may predispose to these recurrences . but eternal vigilance and regular imaging are mandatory to detect recurrences . another point worthy of note\nis why this phenomenon is not seen with respect to other benign tumors like meningiomas or even malignant tumors .", "answer": "the aim was to present a rare case of recurrent craniopharyngioma remote from the primary site of origin . \n a young girl was operated for sellar region craniopharyngioma . for a small residual tumor \n , she underwent radiotherapy . \n follow - up imaging did not reveal any residual tumor or recurrence . \n surveillance magnetic resonance imaging after 5 years revealed a recurrence in the right sylvian fissure . \n this tumor was totally excised . \n recurrence of craniopharyngioma is well - known , but recurrence at a site remote from the original site after radiotherapy is extremely rare . \n one such case is being presented .", "id": 500} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninsulinoma is a rare neuroendocrine tumor of the pancreas , accounting for 2% of all pancreatic tumors .\nits occurrence is 1:100,000 and it is more common in women over 50 years of age .\ninsulinomas are usually solitary benign tumors , and less than 10% of them are malignant2,3 ) .\nmalignant insulinomas are diagnosed when metastases occur , but distinguishing malignant insulinomas from benign insulinomas is difficult histologically .\nfocal nodular hyperplasia ( fnh ) represents a localized liver cell hyperplasia containing central and/or stellate fibrous scar4 ) .\nchildren account for only 7% of cases of this tumor , and fnh comprises only 2% of all pediatric liver tumors5,6 ) .\nwe report a case of an insulinoma in an 11-year - old child who subsequently developed multifocal nodular lesions of the liver after resections of the insulinoma .\nan 11-year - old girl was admitted for evaluation of recurrent seizures that had begun 5 months before admittance , especially in the morning , despite administration of oral antiepileptic medication .\nalthough brain magnetic resonance imaging ( mri ) and electroencephalogram studies were all normal 2 months before admittance , she again had a seizure and was prescribed with oral levetiracetam to control her seizure attacks .\nten days prior to admittance , the patient had been brought to the emergency department due to an ongoing seizure .\nher serum glucose level was 35 mg / dl and she was controlled seizure by intravenous infusion of 10% dextrose fluids .\nafter discharge , she experienced 3 additional attacks of seizures that had been relieved by grape juice .\nupon admittance , her height was 161.3 cm ( > 97th percentile ) , and her weight was 47.6 kg ( 75th < percentile<90th ) and her body mass index was 18.8 kg / m ( 50th < percentile<75th ) . all vital signs and the physical characteristics of the organs were all normal .\ninitial laboratory results , including a serum glucose level of 104 mg / dl , were unremarkable .\na 72-hour fast test was initiated , and the patient demonstrated drowsiness , trembling , and tachycardia after less than 6 hours .\nlaboratory test results during the fast period showed hyperinsulinemic hypoglycemia without ketonuria : the serum insulin level was 50.1 u / ml ( normal range , 2.0 - 25.0 u / ml ) , serum c - peptide level was 1.81 ng / ml ( 0.59 - 1.56 ng / ml ) , and plasma glucose level was 21 mg / dl ( 70 - 100 mg / dl ) .\nsubsequent glucagon stimulation test results revealed an increase in insulin level to 85.8 u / ml .\nthe mri studies revealed a solid mass , 3 cm2.4 cm in size , with lobulated margins , in the pancreatic tail ( fig .\n1 ) , with no metastasis , while abdominal ultrasonography ( us ) and computed tomography ( ct ) results were normal .\nthe tumor was easily detected due to its superficial position at the end of the pancreatic tail , and no enlarged lymph nodes were detected around the pancreas or metastatic lesions in the abdominal cavity .\nthe pathologic examination indicated that the resected tumor ( 3 cm3 cm2.5 cm in size ) was multilobulated and not encapsulated , and no necrosis was evident .\nthe tumor was of neuroendocrine origin , well differentiated , with an intermediate grade ( mitoses 4/10 high - power fields ) with angioinvasion .\nthe ki-67 index , a cellular marker for proliferation which < 3% means a low grade tumor , was 1% ( fig .\n, fasting serum glucose levels were maintained between 110 to 140 mg / dl without any treatment .\nfollow - up mri studies were conducted 2 months after tumor removal , and revealed multiple hypointense nodular lesions in the hepatic segments s5 , s6 , and s8 ( fig .\nus - guided needle biopsy of the liver yielded a diagnosis of the lesions as fnh , with no necrosis or mitotic activity was noted . since then\nthe patient has been free of hypoglycemia for 2 years , and there was not the learning problem in her school .\nrecent mri studies have shown that the fnh lesions have decreased in size , without any evidence of metastasis .\nthe classical diagnosis of insulinomas is based on whipple 's triad : hypoglycemia of serum glucose lower than 50 mg / dl , neuroglycopenic symptoms ( such as behavioral or personality changes and seizure ) , and prompt alleviation of symptoms after administering glucose .\nmalignant insulinoma is extremely rare in the pediatric population , with only a few cases reported in the english literature .\ndistinctions between benign and malignant insulinomas are based on metastasis or the invasion of the primary tumor into the lymph nodes , tissues , or other organs8 ) .\ninsulinomas larger than 3 cm are also more likely be malignant , with local invasion or metastases to the liver9 ) . recently ,\njanem et al.3 ) reported a pediatric case of malignant insulinoma in the context of a literature review of 9 preceding cases . among the nine cases , five cases showed liver metastasis , two cases showed capsular invasion , and data for the remaining two cases were not available .\nconsidering the criteria of malignant insulinoma , which require metastasis or local invasion of adjacent lymph nodes or tissues , these five cases with liver metastasis - together with the case reported by janem et al.3 ) involving metastasis to the liver , bone , and bone marrow - may be the only true reported malignant insulinomas to date .\nhowever , sata et al.10 ) and janez11 ) reported cases of malignant insulinomas initially diagnosed as benign , that recurred as liver metastases 8 and 15 years , respectively , after initial removal .\nneither of these studies confirmed metastasis or invasion during the initial surgery or in subsequent histologic exams of the initial specimens .\nthus , insulinomas may be considered as tentatively malignant because these rare tumors have unpredictable features and progression through the body .\nneuroendocrine tumors have recently been identified as risk factors that are strongly associated with aggressive tumor behavior leading to malignancy12 ) .\nhistopathologic grading of tumor cells based on mitosis may aid in prediction of future insulinoma outcomes , as the biologic behavior of low - grade tumors is often rather nonaggressive , whereas high - grade tumors are very aggressive12 ) .\nour histopathologic findings showed a well - differentiated , intermediate neuroendocrine tumor of the resected insulinoma and our operation field findings revealed no evidence of metastasis .\nnevertheless , the possibility of malignancy was included due to the size of the tumor and its histological angioinvasion . the unusual multifocal hepatic lesions following tumor removal\nit has been infrequently documented in adults and children following chemotherapy , radiotherapy , and stem cell transplantation for different types of solid tumors13 ) .\nthe cause is unknown , although one hypothesis is that obstruction of hepatic vessels or abnormal vascularization could account for fnh , as suggested by the reported association with clinical and anatomic findings like hypoplasia or agenesis of the portal vein , vascular malformations , hemangioma and vascular dysplasia , budd - chiari syndrome , and hereditary hemorrhagic telangiectasia14 ) .\nalthough ct and mri findings of fnh may commonly include the presence of a central scar and typical enhancement patterns , biopsy is necessary in difficult cases with differential diagnosis of liver adenomas and carcinomas .\ntreatment recommendations regarding fnh are based on longitudinal follow - up of a small series of patients . because fnh is a benign tumor with rare complications , most lesions are followed nonoperatively with serial us or mri , provided that a reliable diagnosis can be achieved using radiologic imaging3,15 ) .\nhepatic lesions can induce diagnostic problems when metastasis must be ruled out . in our case ,\nhepatic nodular lesions were identified as fnh by needle biopsy , but the association of an insulinoma with the fnh after surgery remains unclear . to our knowledge , this is the first pediatric case report of an insulinoma in which diagnosis was confused due to newly discovered hepatic lesions after tumor resection .\nclose observation and follow - up imaging studies are required in patients who show malignant potential on histopathologic findings .", "answer": "insulinoma , which arises from insulin - producing pancreatic beta cells , is a rare tumor in children . \n only 5%-10% of insulinomas are malignant and undergo metastasis . \n we report a case of an 11-year - old girl who experienced hypoglycemia - related seizures induced by an insulinoma ; after resection of the primary tumor , she developed hepatic focal nodular hyperplasia ( fnh ) . \n laboratory test results indicated marked hypoglycemia with hyperinsulinemia . abdominal ultrasonography ( us ) and computed tomography results were normal ; however , magnetic resonance imaging ( mri ) showed a solid mass in the pancreatic tail . \n therefore , laparoscopic distal pancreatectomy was performed . \n two months after the surgery , an abdominal mri revealed multiple nodular lesions in the liver . \n an us - guided liver biopsy was then performed , and histological examination revealed fnh without necrosis or mitotic activity . \n the patient has been free of hypoglycemia for 2 years , and recent mri studies showed a decrease in the size of fnh lesions , without any evidence of metastasis . \n even though no metastatic lesions are noted on imaging , close observation and follow - up imaging studies are required in a child with insulinoma that has malignant potential on histopathologic findings .", "id": 501} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin humans , cryoglobulinemia can be responsible for a membranoproliferative glomerulonephritis ( mpgn ) , which is characterized by the formation and/or deposition of immunoglobulins ( igs ) and complement in the glomeruli , followed by an influx of inflammatory cells [ 1 , 2 , 3 ] .\nsince the early studies to investigate complement activation by immune complexes in experimental nephrotoxic nephritis , the complement system has been considered to play an important proinflammatory role in the glomerulus [ 5 , 6 ] . in cryoglobulinemia , however , there is no clear evidence that complement activation is central in mediating tissue damage by immune deposits .\nresults have been obtained in mice by trendelenburg et al . , who analyzed the role of complement in the pathogenesis of initial glomerular inflammation induced by murine 619 igg3 monoclonal cryoglobulins .\ntheir results indicated that complement c5 has a predominant role in neutrophil recruitment as c5-deficient mice had significantly reduced glomerular infiltration by polymorphonuclear neutrophils .\nthis is of particular interest , as the monoclonal complement c5-blocking antibody eculizumab could offer a promising therapeutic option for patients with cryoglobulin - induced glomerulonephritis .\ncryoglobulinemia is a rare disease and is characterized by igs that precipitate in the cold .\ndepending on the clonality of the precipitating igs , three types of cryoglobulinemia can be distinguished .\ntype i cryoglobulinemia consists of a single monoclonal cryoprecipitable ig , whereas type ii and iii cryoglobulins are mixed , i.e. composed of monoclonal ( type ii ) and polyclonal ( type iii ) antibodies with rheumatoid factor activity against other igs .\nmixed cryoglobulinemia may be associated with numerous infectious and immunological diseases as well as lymphatic malignancies .\nin particular , mixed cryoglobulinemia type ii is strongly associated with chronic hepatitis c , and nowadays rarely appears as an isolated disease , i.e. the so - called essential cryoglobulinemia .\nclinically , cryoglobulinemia manifests itself with symptoms like weakness and arthralgias and variable cutaneous and visceral organ involvement [ 9 , 10 ] .\nit is poorer in patients with renal involvement , liver failure , lymphoproliferative disease and malignancies .\nsteroids suppress inflammation with success in some patients , but additional plasmapheresis to remove circulating cryoglobulins and immunosuppressive treatment to inhibit the formation of new cryoglobulins are often necessary [ 11 , 12 , 13 ] .\n, usa ) is a monoclonal antibody that targets complement c5 and prevents the cytolytic and proinflammatory effects of complement activation .\nit effectively reduces intravascular hemolysis , thereby improving anemia and quality of life and decreases transfusion requirements [ 15 , 16 ] .\nsince the initial validation of inhibition of a complement component as a therapeutic target , the field for the use of eculizumab has been expanded . recently\n, eculizumab has been approved from the fda for the treatment of patients with atypical hemolytic uremic syndrome , in whom the control of complement activation is insufficient .\nfurthermore , eculizumab has been successfully used preemptive prior to kidney transplantation [ 18 , 19 ] or postoperatively to prevent disease recurrence in the allograft [ 20 , 21 , 22 ] in several cases with complement disorder - associated atypical hemolytic uremic syndrome . here , we report on an exceptional case of mixed essential cryoglobulinemia with severe glomerulonephritis characterized by a prominent infiltration of the glomeruli by neutrophils . a 1-patient clinical trial of eculizumab was attempted to investigate whether complement inhibition would be sufficient to inhibit this relapsing glomerulonephritis .\nthe initial partial response was , however , not sustained , and the patient returned to intermittent plasmapheresis .\na 55-year - old woman was diagnosed with a mixed type ii cryoglobulinemia ( monoclonal igm - kappa and polyclonal igg ) and immune complex - mediated glomerulonephritis in may 2006 .\nshe developed an acute nephritic syndrome with pathological urinary sediment ( i.e. dysmorphic erythrocytes , cellular casts and leucocytes ) , high proteinuria ( 7 g / day ) , arterial hypertension , volume overload and moderate renal function impairment , which got worse over time .\nfurther , she suffered from weakness and arthralgias , but other organ manifestations besides the kidney were not present .\nthe first renal biopsy showed endocapillary hypercellularity with infiltration of mononuclear cells , an unusual high number of neutrophils , and subendothelial immune deposits , which were positive for igm as well as complement c3 and c5b-9 , resembling acute poststreptococcal glomerulonephritis ; however , classical humps were missing ( fig .\nextensive screening for an infectious disease ( i.e. serological testing and pcr for hiv , hcv , hbv , cmv and ebv ) and malignancy ( bone marrow biopsy , computed tomography of the chest and abdominal organs ) was negative .\nfurther , autoantibodies were negative ( ana , anca , anti - dna , antiphospholipid antibodies ) except for rheumatoid factor , with a titer > 1/10,000 .\na second renal biopsy 1 year later showed early stage mpgn with a still high number of neutrophils , which was interpreted as a progression of disease .\nthe patient was unresponsive to high - dose steroids and subsequently received cyclophosphamide pulse therapy , mycophenolat mofetil and two courses of the monoclonal anti - cd20 antibody rituximab . these immunosuppressive therapies all failed to get the cryoglobulin - induced glomerulonephritis under control .\non october 2006 , once to twice weekly plasmapheresis was started with success . however , plasmapheresis was complicated by two catheter - related blood stream infections .\nin addition , she suffered from headache and complained about unpleasant diaphoresis during the procedures .\nat the request of the patient , plasmapheresis was interrupted several times with prompt disease relapses manifested by an increase in serum creatinine and proteinuria , and reinstitution of intensive plasmapheresis .\nthus , we designed a protocol to test whether eculizumab could replace plasmapheresis at the time of a relapse .\nthe protocol was approved by the local ethical committee , and informed consent was provided in accordance with the declaration of helsinki .\ncriteria for treatment success were : ( i ) prevention of progression as determined by maintenance or improvement in renal function , ( ii ) reduction of proteinuria , and ( iii ) no appearance of new extrarenal disease manifestations . in june 2011 ,\nthe study was started after the last series of plasma exchange , with a continuous surveillance of renal function and clinical signs of relapse .\nas expected from previous intervals between plasmapheresis series , it took 3 weeks until relapse .\neculizumab was dosed at 900 mg intravenously every 7 days for 4 weeks , at 1,200 mg 7 days later , and another dose of 1,200 mg 14 days later . at that time of initiating eculizumab therapy ,\nmol / l ( egfr 13 ml / min ) , proteinuria was 8 g / day and the patient still had nephritic urinary sediment .\nthe patient had been vaccinated against neisseria meningitis 14 days prior to receive the first dose of eculizumab .\n2 shows the clinical course and renal function ( i.e. serum creatinine and proteinuria ) , before and after initiating eculizumab .\nblood samples were drawn to control blood concentrations of eculizumab and blockage of the complement system during the treatment .\ncomplement activity was shown to be blocked using a hemolytic assay ( ch50 ) and by the drop to background of the high levels of soluble c5b-9 ( microvue complement sc5b-9 plus ; quidel corporation , san diego , calif .\nthe eculizumab infusions were well tolerated and the patient reported an improvement in her well - being .\nnevertheless , without plasmapheresis the blockage of the terminal complement was not sufficient to control the disease .\nproteinuria remained at high levels of 68 g / day , hematuria persisted and renal function remained stable for some weeks before deteriorating .\nafter 7 weeks of therapy , the patient was urgently admitted to hospital because of fluid overload .\nto our knowledge , this is the first report of a clinical trial to investigate the monoclonal complement inhibitor eculizumab in a patient with mixed cryoglobulinemia and severe glomerulonephritis .\nthe unique features of the cryoglobulinemic mpgn in this patient were the resistance to treatments such as steroids , cyclophosphamide and rituximab , the presence of high numbers of neutrophils in two renal biopsies taken at 1-year interval ( on both occasions at the time of a severe relapse ) , and the prompt response to plasmapheresis .\nall these features suggested that complement was a major player in the disease process : indeed complement was activated and deposited in the glomeruli , and complement factor c5a is known to be a highly active chemotactic agent for neutrophils .\nin addition , recently macrophages have been shown to be central to the nephritis in a model of murine cryoglobulinemic mpgn .\nthe improvement felt by the patient and the stabilization of the creatinine level after initiation of eculizumab suggested that complement might be involved in the inflammation and tissue damage induced by cryoglobulins . however , it became evident after 7 weeks that there was no improvement , rather a slow deterioration of renal function with ongoing signs of active nephritis in the urinary sediment .\nthis observation does , however , not exclude a role for complement in cryoglobulin - induced glomerulonephritis .\nfor instance , we do not know whether complement blockade would prevent a relapse , i.e. whether complement might induce a cascade of inflammatory events , which then become independent of continuous complement activation .\nfurther , one can argue that the blockage of c5 by eculizumab plays a central role to prevent the chemotactic function of c5a for the recruitment of neutrophils .\nonce they have invaded the glomerulus where the inflammatory processes take place , they act independently of complement c5a , which has no proinflammatory effects .\nthis would be an argument for a prophylactic and sustained use of eculizumab in patients with cryoglobulinemia when the disease is in remission and against its use as a salvage therapy in disease relapse , to induce a more prolonged remission or reduce the frequency of relapses .\n, where the c5-deficient mice had impressively less influx of neutrophils , as their experimental model of cryoglobulin - induced glomerulonephritis rather resembles a model of preemptive blockage of c5a to prevent glomerular inflammation just at the beginning and not when the inflammatory process is fully developed as it is in case of a relapse .\nin addition , eculizumab will not prevent the deposition of c3 fragments and release of c3a , which by themselves might interact with complement receptors on mesangial cells , macrophages / monocytes and neutrophils and activate these cells .\nusually , the development of clinical therapy protocols relies on evidence - based guidelines that mainly focus on randomized , controlled trials ; however , for rare diseases , such as in the present case of essential cyoglobulinemia , treatment options rely on similarities to other diseases and the understanding of the pathological process on experimental data obtained in animal models . since\nhuman data of cryoglobulinemia are scarce , the present 1-patient trial report demonstrating the response to eculizumab whether considered partially positive or negative might be of use for the medical community .", "answer": "cryoglobulinemia induces an immune complex - mediated glomerulonephritis that is characterized by the presence of large immune deposits , including complement c3 and c5b-9 , marked macrophage influx and mesangial cell proliferation . \n the precise role of complement in cryoglobulin - induced glomerulonephritis in humans remains unclear , whereas in mice there has been evidence that complement activation might be a central factor favoring glomerular inflammation , particularly by the recruitment of neutrophils . \n we report on an exceptional case of cryoglobulin - induced glomerulonephritis in a patient with mixed essential cryoglobulinemia type ii . \n the clinical features included relapsing proteinuria and renal function impairment that were controlled by plasmapheresis . \n complement was low in plasma and two renal biopsies at 1-year interval showed prominent immunoglobulin and complement deposits , with unusual high numbers of neutrophils . in a 1-patient clinical trial , we tested whether the monoclonal anti - c5 antibody eculizumab would be sufficient to control renal function at the time of a relapse . \n although during the initial weeks renal function was stabilized , slow increase in creatinine could not be controlled by this treatment , so that plasmapheresis was reinstituted . \n this result suggests that despite evidence for a role of complement in enhancing renal damage in this patient , other inflammatory processes dominated .", "id": 502} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the 19th century , robert koch postulated a causal relationship between a pathogenic microbe and a disease .\nthis was later extended to the role of autoantibodies in the pathogenesis of human disease by witebsky et al . .\nin 1957 , they proposed the fulfillment of several criteria to proof the pathogenic effects of autoantibodies , namely , the direct demonstration of free , circulating , or cell - bound antibodies by indirect means , the recognition of specific antigen against which the antibody is directed , the production of antibodies against the same antigen in experimental animals and finally the appearance of pathological changes in the corresponding tissues of an actively sensitized experimental model that is similar to that in the human disease . \nmolecular mimicry was proposed as a mechanism by which infectious agents trigger an immune response against autoantigens , resulting in the development of autoimmune diseases .\nsimilar criteria must be satisfied to conclude that a disease is triggered by molecular mimicry .\nthey are as follows : ( i ) the establishment of an epidemiological association between the infectious agent and the immune - mediated disease ; ( ii ) the identification of t cells or antibodies directed against the patient 's target antigens ; ( iii ) the identification of microbial mimics of the target antigen ; ( iv ) reproduction of the disease in an animal model .\nalthough there have been a number of diseases proposed to exhibit the mechanism of molecular mimicry , none has been proven in examples of human diseases based on fulfilment of all four criteria .\nguillain - barr syndrome ( gbs ) , characterized by limb weakness and areflexia , has become the most frequent cause of acute flaccid paralysis since the near elimination of poliomyelitis in the world .\nmost gbs patients have had either gastrointestinal or upper respiratory symptoms one to three weeks prior to the onset of their neurological symptoms , making gbs the prototype of postinfectious autoimmune diseases .\ngbs can be classified into two major subtypes , acute inflammatory demyelinating polyneuropathy ( aidp ) and acute motor axonal neuropathy ( aman ) depending on whether the myelin or the axonal components of the peripheral nerves are affected .\nean can be transferred to animals by t cells sensitized to peripheral nerve proteins such as p2 protein .\nhowever , no investigators have shown conclusive evidence that such autoreactive t - cell response is seen in patients with gbs , indicating that ean is not a true model of aidp . in this paper\n, we describe the development of a true model of aman , which fulfills all the four criteria of molecular mimicry as well as witebsky 's postulate as stated above .\nthis verifies gbs as the first paradigm of an autoimmune disease triggered by molecular mimicry .\nwe also discuss how this disease model has helped uncover the precise mechanism of muscle weakness in gbs , which will potentially lead to the development of better treatments .\ngram - negative bacterium campylobacter jejuni , a leading cause of acute gastroenteritis , is the most common antecedent microorganism in gbs .\na prospective case - control study detected evidence of recent c. jejuni infection in 26% of patients with gbs in comparison to only 2% of the household controls ( a member of the patient 's household ) and 1% of the age - matched hospital controls .\na study showed that c. jejuni infection was associated with aman , but not aidp , although this finding has yet to be verified by other investigators .\nautoantibodies are considered to be the pathogenic components which trigger gbs because plasma exchange is proven to be an effective treatment in gbs .\ngangliosides constitute a large family of predominantly cell - surface glycosphingolipids bearing a ceramide moiety anchored in the external leaflet of the lipid bilayer and a sialylated oligosaccharide core exposed in the extracellular space .\nautopsy studies show that , in aman , igg is deposited on the axolemma of the spinal anterior root , indicating that igg , which binds effectively with complement , is an important factor in the development of aman .\npatients who develop aman subsequent to c. jejuni enteritis have igg antibodies against gm1 .\nin contrast , patients who have c. jejuni enteritis with no neurological sequelae did not have similar autoantibodies .\nthese findings suggest that gm1 is an autoantigen for igg antibodies in patients with aman subsequent to c. jejuni enteritis .\nigg anti - gd1a antibodies are also associated with aman subsequent to c. jejuni infection .\nlipo - oligosaccharides ( loss ) are a family of phosphorylated glycolipids anchored on the outer surface membrane of c. jejuni .\na c. jejuni strain isolated from an aman patient carrying igg anti - gm1 antibody expressed an oligosaccharide structure [ gal 13 galnac 14 ( neuac 2 - 3 ) gal ] which protruded from the los core ( figure 1 ) .\nthis terminal structure was identical to that of the terminal tetrasaccharide of the gm1 ganglioside .\nthis was the first definitive evidence of molecular mimicry between human peripheral nerves and antecedent agents in gbs .\nfurther evidence regarding the role of antiganglioside antibodies in gbs came in the form of adverse reactions to therapeutic gangliosides extracted from bovine brain tissue .\nthese were previously used in the treatment of various neurological disorders . in a study investigating seven patients who developed aman following intravenous bovine brain ganglioside administration\n, anti - gm1 antibodies were discovered in six patients and anti - gd1a and -gt1b antibodies in one patient .\nthese findings set the scene for the work done in the development of a suitable experimental animal model for gbs .\nan aman model was established by the sensitization of rabbits with a bovine brain ganglioside mixture that included gm1 or with an isolated gm1 .\nthe rabbits developed high titres of igg anti - gm1 antibodies , followed by an acute onset of flaccid limb weakness with a monophasic course .\npathological findings in their peripheral nerves showed predominant wallerian - like degeneration with neither lymphocytic infiltration nor demyelination features .\nigg was deposited on the axons of the anterior roots , internodal axolemmas , and nodes of ranvier .\ncauda equina and spinal nerve root specimens from the paralyzed rabbits showed macrophage infiltration in the periaxonal space .\nthese findings correspond well with pathological findings for human aman [ 10 , 18 ] .\nthe most straightforward way of verifying that molecular mimicry between microbes and autoantigens cause gbs is to establish a gbs model by the immunization of animals with components of antecedent infectious agents .\nan aman model was established by the immunization of rabbits with c. jejuni los bearing a gm1-like structure .\non sensitization with this gm1-like los , rabbits developed igg anti - gm1 antibodies and subsequent flaccid limb weakness ( figure 2 ) .\ntheir nerve roots had occasional macrophages in the periaxonal spaces surrounded by an almost intact myelin sheath .\nthese findings , which are compatible with the features of human aman , provided the evidence that rabbits inoculated with c. jejuni los constitute a valid aman model .\nthis represents the first replica of human autoimmune disease in an animal model immunized by a microbial mimic of a self - antigen .\nin contrast to the active immunization models above , a passive transfer model was developed to further proof the molecular mimicry theory .\nex vivo nerve - muscle preparations from gd1a - overexpressing mice were exposed to mouse igg anti - gd1a monoclonal antibodies in the presence of a complement source .\nthis allowed the morphological and neurophysiological features of such an exposure to be investigated further .\ndense antibody and complement deposits were shown to only be present on the presynaptic motor axons .\nthis was accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function .\na similar paralyzing effect was found when human sera with igg anti - gd1a reactivity were used instead .\nthese findings indicate that anti - gd1a antibodies arise from molecular mimicry and are the likely trigger of peripheral nerve injury . in summary\n, gbs is the first true model of molecular mimicry having fulfilled all four criteria as follows : ( i ) establishment of an epidemiological association between gbs and c. jejuni infection by a prospective case - control study , ( ii ) identification of autoantibodies against gm1 and gd1a gangliosides in patients with aman subsequent to c. jejuni enteritis [ 11 , 12 ] , ( iii ) identification of molecular mimicry between gm1 or gd1a and los of c. jejuni isolated from aman [ 13 , 14 ] , and ( iv ) reproduction of the aman models by active immunization of rabbits with gm1 or the c. jejuni los [ 16 , 19 ] as well as by passive transfer of anti - gd1a antibodies in mice .\nthis makes gbs the first disease in humans to verify that an autoimmune disease is triggered by molecular mimicry .\nin both human and rabbit aman , the earliest pathological changes consist of lengthening of the node of ranvier with distortion of the paranodal myelin [ 17 , 21 ] .\nvoltage - gated sodium channel dysfunction is postulated to occur at the nodes of ranvier .\nthere has been some controversy as to whether anti - gm1 antibodies truly affect sodium channels at the nodes of ranvier [ 23 , 24 ] . in the spinal anterior roots of aman rabbits ,\nthis binding of autoantibodies triggers complement activation with deposition of c3 components followed by membrane attack complex formation at the nodal axolemma .\nthe sodium channel clusters are then altered by the destruction of their stabilizing components which include the axonal cytoskeleton at nodes , schwann cell microvilli , and paranodal axo - glial junctions .\nthis apparent disappearance of sodium channel clusters significantly lowers the safety factor for impulse transmission , thus causing muscle weakness in aman .\nthis is a novel mechanism by which autoantibodies can modulate sodium channel properties to cause the development of certain neurological disorders .\nplasma exchange and intravenous immunoglobulins are equally effective treatments in gbs . despite the administration of either immunotherapeutic agent , there are still mortality and significant morbidity in patients with gbs ; 310% death and 20% immobile after 6 months .\nresearch into new treatment options to improve the final outcome of gbs is urgently required .\nas previously described , complement activation products are deposited on the outer membrane of schwann cells in aidp patients , and on the axolemma of motor fibres in aman .\nthese postmortem studies show that complement activation followed by membrane attack complex formation is an important mechanism for the glial and neuronal injury seen in gbs .\nthis suggests that complement inhibitors have the potential of being a new , more rational treatment for gbs .\nnafamostat mesilate is a synthetic serine protease inhibitor that has been used clinically in japan for over 20 years with no serious adverse effects to patients .\nas the complement system contains several serine proteases such as c1r , c1s , and c3/c5 convertases , nafamostat mesilate can efficiently inhibit these serine proteases , thus blocking the formation of the membrane attack complex .\nthis inhibition of complement deposition and sodium channel cluster disappearance has been demonstrated in aman rabbits .\nthese experimental findings along with the autopsy findings would justify establishing clinical trials to investigate the use of complement inhibitors as a potential treatment for gbs .\nin this paper , we have demonstrated how the animal model of aman has contributed to the proof of the molecular mimicry theory .\nonly the first criterion has been achieved with the association of aidp with cytomegalovirus infection . until the target antigen in aidp\nis ascertained , identification of its microbial mimics and reproduction of the disease in an animal model remain unresolved .", "answer": "molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases , and this hypothesis is proven in guillain - barr syndrome . \n guillain - barr syndrome , the most frequent cause of acute neuromuscular paralysis , sometimes occurs after campylobacter jejuni enteritis . \n gangliosides are predominantly cell - surface glycolipids highly expressed in nervous tissue , whilst lipo - oligosaccharides are major components of the gram - negative bacterium c. jejuni outer membrane . \n igg autoantibodies to gm1 ganglioside were found in the sera from patients with guillain - barr syndrome . \n molecular mimicry was demonstrated between gm1 and lipo - oligosaccharide of c. jejuni isolated from the patients . \n disease models by sensitization of rabbits with gm1 and c. jejuni lipo - oligosaccharide were established . \n guillain - barr syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry . \n its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in guillain - barr syndrome .", "id": 503} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan initial search using three different search engines : google ( www.google.com ) , yahoo ( www.yahoo.com ) , and ask jeeves ( www.ask.com ) for the term thumb sucking habit was performed on 20 march 2014 .\nit was found that google ( www.google.com , mountain view , ca ) incorporated the vast majority of the links to websites which the other two search engines produced and , therefore , the search for this investigation was conducted using google .\nas it is unlikely that patients will investigate beyond the first few pages of a search , the initial 100 links generated by google were considered .\nimages of all websites in the study were stored for any necessary future analysis . the discern instrument\ndiscern is a validated rating tool that can be used by health professionals and the general public to assess the quality of health information contained on the internet .\nthe discern instrument asks 16 questions related to the quality of a medical information website table 1 .\neach question is given a score from 1 to 5 , with 1 being no , 2 to 4 being partially , and 5 being yes\n. the last question pertains to the overall quality of the website and is rated 1 ( poor ) to 5 ( good quality ) .\nthis requires compliance with these eight criteria : authority ( give qualifications of authors ) , complementarity ( information to support , not replace ) , confidentiality ( respect the privacy of site users ) , attribution ( cite the sources and dates of medical information ) , justifiability ( ability to back claims ) , transparency ( accessibility , provide valid contact details ) , financial disclosure ( provide details of funding ) , and advertising ( clearly distinguish advertising from editorial content ) .\nthe hon website was used to confirm the validity of each site presenting an hon seal .\nwebsites were included in the investigation if they provided information pertaining to the thumb sucking habit .\nwebsites that were unrelated to search term or only provided a list of website links were removed . sponsored links and banner advertisements\nwere excluded as they are normally ignored . for profit websites were excluded : if their only intention was to sell a product , if the site promised quick and unrealistic dramatic results , made claims that one remedy will cure a variety of illnesses through some miraculous breakthrough , or used excessive sensational writing .\njournal articles , news , video feeds , academic press , abstracts listings , discussion group , and duplicate sites were also eliminated .\nwebsites were included in the investigation if they provided information pertaining to the thumb sucking habit .\nwebsites that were unrelated to search term or only provided a list of website links were removed . sponsored links and banner advertisements\nwere excluded as they are normally ignored . for profit websites were excluded : if their only intention was to sell a product , if the site promised quick and unrealistic dramatic results , made claims that one remedy will cure a variety of illnesses through some miraculous breakthrough , or used excessive sensational writing .\njournal articles , news , video feeds , academic press , abstracts listings , discussion group , and duplicate sites were also eliminated .\nsixty - four of the 100 websites were excluded from the analysis as they did not meet inclusion criteria . of the remaining 36 websites that were scored ,\ndiscern indicated the majority of websites fell well below the maximum score . the maximum score achieved by one of the websites according to the discern tool was 55 of 80 , and the lowest score achieved was 16 of 80 .\nthe five websites with the highest quality information in relation to thumb sucking was : \n children.webmd.com : 55healthmantra.com : 54medicinenet.com : 44users.forthnet.gr : 41ivillage.com : 37 . \n \nchildren.webmd.com : 55 users.forthnet.gr : 41 discern scores for the 36 websites in relation to the hon seal , out of 36 websites only three had hon seal .\nas of today , there are no standards required for medical information on the internet , taking advantage of this ; some websites that appear to be educational are actually promotional in nature while others may be inefficient , incomplete , out of date , difficult to understand , or contain conflicting information .\nthis is the first study investigating the quality of information available on the internet relating to thumb sucking habit , at a single moment in time .\nwe used google as the internet search engine for this investigation after an initial search using yahoo and ask jeeves as well found that there was considerable overlap among the websites that google would find .\nthe other search engines such as bing ( www.bing.com ) and aol ( www.search.aol.com ) are also available .\ngoogle was selected because is the most popular search engine , examines all aspects of a pages content and the content of the pages linking to it .\nno one can buy a higher ranking with their software , which makes it an easy way to find high - quality sites .\nin addition , it may find many pages that are off - line for many other search engines , it updates their index very often by recalculating the page rankings of each of the websites and the fluctuations usually occur toward the end of the month .\nthe results of our study indicated that very few sites achieve high standards according to the discern tool .\nin fact , none of the websites scored five points in all the 16 questionnaires .\nthe discern project is based at the division of public health and primary care of the institute of health sciences of the university of oxford ( united kingdom ) , and is financed by the british national health service executive research and development program .\nit has been designed to help users to evaluate the quality of written information on treatment options , and to facilitate the generation of evidence - based data .\nthe discern is a validated and reliable instrument . in our study , the item does it describes how treatment choices can affect quality of life ?\n yielded a very low score in all the websites , which were assessed , which is in line with lopez - jornet and camacho - alonso . although discern has been criticized for not analyzing the quality of the information on websites in significant detail . when compared to other tools such as the jama benchmarks , the discern tool has been shown to have good internal consistency and is user - friendly . in this\nrespect , clinical teams can use the discern tool to evaluate websites that patients may suggest to determine if the information they are likely to find is of use for other patients .\nthe discern questionnaire is a valid and reliable instrument for analyzing written consumer health information .\nit is the first standardized quality index of consumer health information that can be used as a critical appraisal tool to evaluate health information by not only health professionals , but also by patients and the general population .\nthis questionnaire was derived systematically with the input of an expert panel , health information providers and patients from a self - help group .\nthis study found that discern score was highly rated among the initial search results displayed and was same with the hon seal .\nthe health on the net foundation criteria were developed by a swiss - based nonprofit , nongovernmental organization that provides certification of websites based on an ethical standard aimed at offering quality health information . \nhealth on the net is established in 1995 and is one of the first uniform resource locator to guide both lay people and those in the medical profession to reliable sources of healthcare information on the internet .\nsites may display the hon code seal if they agree to comply with the standards listed , and they are subjected to random audits for compliance .\nthe external accreditation of quality of health - related websites is not an easy task as it would be an enormous and costly task requiring a large staff with expertise in varying fields to monitor thousands of medical sites .\nhon 's mission is to guide internet users to reliable , understandable , accessible , and trustworthy sources of medical and health information .\ntherefore , the internet users do not have a way to identify the quality sites unless ; they have a medical background or perform a scientific immersion in the topic . in light of the results of the present study ,\nthe internet is a potentially powerful tool for patients to search for health - related information , there are many sources that when encountered , may mislead them about their diagnosis , treatment , and potential outcomes . in the extreme , patients may feel a false empowerment to self - diagnose and treat , leading to disastrous results . despite these concerns ,\nit is likely that the use of the internet by patients will continue to increase in the future .\nit is , therefore , important for the patients to exercise caution when relying on the internet for health - related information .\npatients should be counseled to avoid commercial websites , except for the most reputable sites and look for the hon code seal of compliance for transparency and accountability .\nit appears that the principles of clarity and full disclosure of sources are still only practiced by a minority of the websites at this point .\nit is our hope that by raising awareness of the poor overall quality and content of the internet information , better accountability may be active or , at least , that patients may become best informed that information on the internet is not accurate or up to date .\napart from the quality of health information on the web , patients also find many websites , presenting health information using highly technical language .\nscientific presentations may be advantageous for researchers and clinicians ; however , this specialized language can be overwhelming and confusing , especially if it is not properly explained .\ntherefore , it is also imperative to systematically assess the presentation of online health information using readability algorithms to ensure that such information is easily assessable to lay audiences in their native language .\npatients seeking thumb sucking habit information on the internet should be encouraged to exercise caution and to utilize only well - known sited and those that display the hon code seal of compliance with transparency and accountability practices . by directing patients to validated websites on the thumb sucking habit", "answer": "aims : the aim of this study was to evaluate the reliability of websites on the thumb sucking habit using discern instrument and health on the net ( hon ) seal code at a single moment in time.subjects and methods : an internet search engine ( www.google.com ) was used to identify websites comprising information on thumb sucking habit . of over 204,000 links for thumb sucking habit , the first 100 were analyzed in detail . after excluding discussion groups , news and video feeds , and removing carbon copy sites , only 36 relevant websites remained , which were then assessed using the discern instrument and hon seal code . using the 16 questions of discern for assessing the reliability and quality of the consumer information which were scored from 1 to 5 , an appropriate index of the quality of the information \n was generated . \n all the assessed websites were also checked for presence or absence of hon seal code.results:the maximum score attainable for an outstanding website is 80 . of the 36 websites that were scored the highest score obtained by one of the websites according to the discern tool was 55 of 80 , and the lowest score achieved was 16 of 80 . \n the websites achieving the maximum and minimum score were children.webmd.com and thebehaviorsolution.com , respectively . \n the hon seal was displayed only in three websites , which were medicinenet.com , righthealth.com , and children.webmd.com.conclusions:by directing patients to validated websites on the thumb sucking habit , clinicians can ensure patients find appropriate information .", "id": 504} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nghent university multidisciplinary research partnership bioinformatics : from nucleotides to networks ; fund for scientific research ( fwo)flanders ( belgium ) ( postdoctoral research fellowship to f.i .\n) ; institute for the promotion of innovation through science and technology in flanders ( iwt - vlaanderen ) ( phd to k.p . )\n; proteomexchange project , funded by the european union 7th framework program under grant agreement number [ 260558 to n.h . ] ; prime - xs project , funded by the european union 7th framework program under grant agreement number [ 262067 to k.g . and l.m . ] .", "answer": "we here present the online protein processing resource ( toppr ; http://iomics.ugent.be/toppr/ ) , an online database that contains thousands of published proteolytically processed sites in human and mouse proteins . \n these cleavage events were identified with combinded fractional diagonal chromatography proteomics technologies , and the resulting database is provided with full data provenance . \n indeed , toppr provides an interactive visual display of the actual fragmentation mass spectrum that led to each identification of a reported processed site , complete with fragment ion annotations and search engine scores . \n apart from warehousing and disseminating these data in an intuitive manner , toppr also provides an online analysis platform , including methods to analyze protease specificity and substrate - centric analyses . \n concretely , toppr supports three ways to retrieve data : ( i ) the retrieval of all substrates for one or more cellular stimuli or assays ; ( ii ) a substrate search by uniprotkb / swiss - prot accession number , entry name or description ; and ( iii ) a motif search that retrieves substrates matching a user - defined protease specificity profile . \n the analysis of the substrates is supported through the presence of a variety of annotations , including predicted secondary structure , known domains and experimentally obtained 3d structure where available . across substrates , substrate orthologs and conserved sequence stretches can also be shown , with icelogo visualization provided for the latter .", "id": 505} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe bacterial isolates were collected throughout finland during 19982007 as described ( 10 ) . of\nbionumerics version 5.1 software ( applied maths , kortrijk , belgium ) was used for sequence assembly .\nallele numbers , sequence types ( sts ) , and clonal complexes ( ccs ) were assigned by using the pubmlst database ( 5 ) .\na serum sensitivity assay was conducted with 73 c. jejuni isolates according to a described protocol ( 8) . the same pool of serum samples from 10 healthy blood donors was used in all experiments . c. jejuni\nall statistical analyses were performed by using graphpad prism version 4.03 ( graphpad software , san diego , ca , usa ) and pasw statistics version 18 ( spss inc . , chicago , il , usa ) .\na total of 72 c. jejuni isolates from blood were successfully typed by mlst ; 1 isolate had a mixed mlst pattern .\nfive isolates were in unassigned sts , and the rest were distributed among 11 ccs ( table ) .\ngenetic relatedness of these isolates was further confirmed by using pulsed - field gel electrophoresis .\n* mlst , multilocus sequence typing ; st , sequence type ; nd , none detected .\nhowever , bacteremia episodes caused by st-677 cc isolates were exclusively diagnosed during the seasonal peak during may august ( figure 1 ) . of c. jejuni blood culture isolates detected during may august , most ( 64% ) were st-677 cc .\nfurthermore , st-677 cc was the most prevalent complex in 4 geographic regions of finland . annual and seasonal distribution of 72 camplyobacter jejuni blood culture isolates belonging either to the st-677 clonal complex ( cc ) or to the other multilocus sequence typing ( mlst ) ccs .\none isolate with a mixed multilocus sequence type was not included . c. jejuni bacteremia was diagnosed during may august ( m a ) or during any other month of the year ( o ) .\nsusceptibility to human serum varied between c. jejuni isolates from different ccs ( figure 2 ) .\nst-677 cc isolates were significantly less susceptible to human serum than all other isolates ( p<0.0001 ) .\nst-45 cc isolates were significantly more susceptible to human serum than all other isolates ( p<0.0001 ) .\npercentage of surviving bacteria in human serum for 73 blood culture isolates of campylobacter jejuni ( cj ) , grouped according to major multilocus sequence typing clonal complexes ( ccs ) , and for controls c. jejuni cj11168 and c. fetus .\nwe characterized a unique collection of 73 c. jejuni isolates from blood obtained during a nationwide study in finland over a 10-year period . despite the high population diversity of c. jejuni , nearly half of the isolates from blood showed clustering within the st-677 cc , a rare cc in other countries ( 12,13 ) .\nthus , invasiveness of blood culture isolates could not be solely explained by their serum resistance , although the predominant isolates of st-677 cc were more serum resistant than other isolates . c. jejuni has high st diversity . as of may 2 , 2013 , a total of 6,564 sts were registered ( 5 ) . in this study , we detected clustering of c. jejuni isolates from blood in an uncommon st-677 cc .\nfurther studies are needed to clarify whether bacterial characteristics might explain this finding . in our previous study , which included human fecal c. jejuni isolates obtained in finland from the mid-1990s through 2007 ,\nwhich is nearly the same period as in the current nationwide study , 11.7% of the isolates belonged to st-677 cc ( 11 ) .\nthe 2 most prevalent ccs in that study , st-45 cc ( 43.6% of fecal isolates ) and st-21 cc ( 19.4% of fecal isolates ) , were detected only among 12 ( 16% ) and 10 ( 14% ) of blood culture isolates , respectively , in the present study .\nst-45 cc and st-21 cc have been shown to be prevalent in several countries ( 4,13 ) . however , our results suggest that these 2 ccs are not common among c. jejuni isolates from blood in finland , which cluster more in the st-677 cc . on the basis of the present results , we speculate that st-677 cc might have a special invasive capability or has adapted to the environment in finland .\nin general , complement - mediated killing of serum - susceptible isolates plays a major role in restricting access of pathogens to the bloodstream . however , available information about possible serum sensitivity of c. jejuni isolates from blood is scarce ( 8,9 ) . in our study of nonselected c. jejuni isolates from blood , susceptibility to human serum varied according to mlst cc . in conclusion , in this nationwide study during a 10-year period in finland , we found by mlst analysis that half of the bacteremia isolates of c. jejuni clustered within an otherwise uncommon st-677 cc . whether this finding indicates special adaptation of st-677 cc to finland or to the human bloodstream\nour findings emphasize the role of using well - defined clinical materials in studies on bacterial pathogenicity and severity of human disease .", "answer": "campylobacter jejuni bacteria are highly diverse enteropathogens . \n seventy - three c. jejuni isolates from blood collected in finland were analyzed by multilocus sequence typing and serum resistance . \n approximately half of the isolates belonged to the otherwise uncommon sequence type 677 clonal complex . \n isolates of this clonal complex were more resistant than other isolates to human serum .", "id": 506} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nabdominal wall pain is a common complaint , and patients can present with it in the acute perioperative period as well as in a chronic pain state.1 pain - relieving therapies are varied , and range from oral medication to interventional procedures .\nrecently , the ultrasound - guided transversus abdominis plane ( tap ) block has become more widely used as an alternative technique for perioperative analgesia for abdominal procedures.24 the abdominal wall is innervated by the anterior division of the lower thoracic and upper lumbar nerves .\nthe nerves course within the fascial plane between the internal oblique and transverse abdominis muscle the tap.5 with this anatomy and its innervation ,\nthe tap block has been shown to provide effective postoperative analgesia , reducing opioid requirements and improving patient satisfaction in the early postoperative period.5 the tap block had been used previously with a nonguided or blind double - pop technique that relies on tactile sensation to determine the appropriate level of local anesthetic infiltration.6 cadaver studies have established the petit triangle , defined medially by the latissimus dorsi muscle , laterally by the external oblique muscle , and inferiorly by the iliac crest .\nthese superficial landmarks , when combined with knowledge of the path of the thoracolumbar nerves , have allowed clinicians to perform blind tap blocks with varying degrees of success.7,8 there are 2 potential pitfalls with a blind tap block .\nfirst , the final needle tip position may be superficial to the transversus abdominis fascial plane , resulting in intramuscular or subcutaneous deposition of the injectate .\nsecond , the final needle tip position may be deep to the intended target , resulting in an intraperitoneal injection .\nboth of these aberrant injections would produce a failed block that results in pain , requiring rescue pain management because of liver laceration or bowel injury , to name just a few complications.9 with the advent of ultrasound guidance , the transversus abdominis fascial plane in which the thoracolumbar nerves reside can be identified and accurately injected with the intended medication.10,11 the ideal volume for a tap block is unknown .\ndifferent techniques ( ie , subcostal versus midaxillary ) have been described , and one study suggests that the more subcostal tap compartment does not communicate with the more lateral triangle of petit.12 volumes of injectate have varied among studies , with some using weight - based volumes versus standard volumes , without any conclusions regarding optimal volume .\na recent retrospective review by abdallah et al13 suggested that 15 ml may be an optimal volume , although findings were inconclusive .\nwe therefore sought to further investigate the spread of various volumes of contrast injected under ultrasound guidance into the tap layer as identified by computed tomography ( ct ) imaging .\nafter receiving approval from the mayo clinic institutional review board , we obtained two unembalmed adult cadaveric torso specimens .\nno specimens exhibited signs of prior surgery , trauma , or major deformity around the abdomen , specifically at the injection sites .\neach cadaver was imaged with a 64-slice ( 2 32 detectors ) siemens somatom definition ct scanner ( siemens healthcare , erlangen , germany ) using a scan protocol consisting of 2-mm axial sections obtained in a soft - tissue kernel .\nall images were interpreted by an experienced musculoskeletal radiologist using a ge advantage workstation ( ge healthcare institute , waukesha , wi , usa ) .\nall ultrasound procedures were performed with a philips cx50 ultrasound machine ( philips healthcare , andover , ma , usa ) , using a 12-mhz linear array transducer with a 35-mm footprint , standard ultrasound gel , a 22-gauge , 89-mm diamond point stainless steel spinal needle ( covidien , mansfield , ma , usa ) , and iodinated contrast agent ( omnipaque 300 , ge healthcare as , oslo , norway ) diluted with 0.9% saline to a concentration of 36 mg / ml ( 10% ) .\nthe tap layer was identified along the midaxillary line by an ultrasound of each cadaver by an experienced sonographer . from superficial to deep\n, the external oblique muscle , internal oblique muscle , and transversus abdominis muscle , including the tap fascial plane between the internal oblique and transversus abdominis muscles , were identified along the midaxillary line between the iliac crest and the subcostal margin , as previously described in the medical literature.4 a 22-gauge , 89-mm spinal needle was advanced under direct ultrasound visualization in a slightly oblique anterior to posterior direction toward the tap . once the needle tip was observed to enter this fascial plane , hydrolocation with 0.9% normal saline was performed to confirm the fascial plane and facilitate better sonographic visualization14 ( figure 1 ) .\neach cadaver was then placed in the ct scanner to verify the anatomical placement of the needle and to obtain baseline imaging of the relevant anatomy prior to contrast administration . following the initial ct scan ,\nthe needle was left in place and extension tubing with a syringe containing the dilute iodinated contrast agent was connected to the needle .\na predetermined amount of contrast was then injected under direct ultrasound visualization into the tap layer , and the cadaveric torso was rescanned using the same ct scan parameters .\nthis procedure was repeated on both sides of each cadaver with different volumes of contrast : cadaver a ( left , 5 ml ; right , 10 ml ) ; cadaver b ( left , 15 ml ; right , 20 ml ) .\nall needle entry points were between the level of the lumbar ( l)3 disk space and the middle of the l4 vertebral body .\ncontrast injected under ultrasound guidance was identified in the tap in both cadavers on ct imaging ( figure 2 and 3 ) .\nintraperitoneal contrast spread was also noted with the 15 ml injection ( figure 3 ) .\ncaudal spread of injected contrast correlated with increasing volumes of injectate ( table 1 ) .\ncaudal distribution was roughly 1 vertebral level ( end plate to end plate ) for the 5 ml injection and 2 vertebral levels for the 10 , 15 , and 20 ml injections .\nanterior - posterior and transverse spread of injected contrast did not correlate with increasing volumes of contrast ( table 1 ) .\nas described in prior studies , there exists a difference in spread when a tap block is performed under ultrasound guidance , versus a nonguided approach to the triangle of petit.13 we chose to perform the injection using ultrasound guidance , with the goal of accurately measuring injectate spread delivered reliably into the transversus abdominis fascial plane .\nit is not uncommon to see a small amount of intramuscular spread of contrast within the tap layer that is likely related to incomplete separation of the fascial planes under pressurization .\nhowever , we were surprised to discover contrast in the peritoneal space despite direct visualization of the needle placement with ultrasound . logically , the ability to see the injection under live imaging guidance should be safer and more successful ; however , the possibility of accessing an unintended target exists , regardless of experience or technique.15,16 the entrance of the needle and thus injectate could pose risk to patients including bowel penetration , injury , or infection . furthermore , when performing injections on cadavers there is no movement such as breathing or bowel peristalsis which may make injections easier but can also make identifying structures more difficult .\nthis is true for the tap block , where the peritoneum can be identified by movement and the muscle layer superficial to it can be identified as the transversus abdominis muscle followed by the internal and external oblique muscles .\nimportantly , in this study , increased volumes of injectate correlated with increased cranial caudal spread , and demonstrated good spread around the midaxillary line where the iliohypogastric , subcostal , and intercostal nerves have been shown to course in the tap.1\nthis study helps further the understanding of injectate spread following ultrasound - guided tap injections .\nspecifically , it suggests that 15 ml provides additional cranial caudal spread and may be an optimal volume of anesthesia .\nthe optimal volume required to achieve an adequate sensory block will vary , depending on the site of planned incision or the severity of abdominal pain .\nfurthermore , the degree of injectate spread may be different for live patients compared with that in fresh cadavers , and in addition , may also vary according to variability of patient height , weight , and previous abdominal surgeries .\ntherefore , further in vivo studies are warranted to investigate the minimum volume of ultrasound - guided injectate required to cause a sensory blockade of the anterior abdominal wall .", "answer": "backgroundultrasound - guided transversus abdominis plane ( tap ) injections are increasingly being used as an alternative to traditional perioperative analgesia in the abdominal region . with the use of a \n blind \n tap block technique , these procedures have had variable success in cadaver and in vivo studies . for more accurate injection with the intended medication , \n ultrasound guidance allows visualization of the correct layer of the abdominal wall planes in which the thoracolumbar nerves reside.objectiveto assess the spread of various volumes of contrast placed under live ultrasound guidance into the tap using computed tomography ( ct).methodsfour tap blocks were performed on 2 fresh frozen cadaver torsos with predetermined contrast volumes of 5 , 10 , 15 , or 20 ml . \n a ct scan of the cadaver was then performed and interpreted by a musculoskeletal radiologist . \n this cadaver study was carried out at a tertiary care academic medical center.resultscranialcaudal spread of injected contrast correlated with increasing injectate volume and was roughly 1 vertebral level ( end plate to end plate ) for the 5 ml injection and 2 vertebral levels for the 10 , 15 , and 20 ml injections . \n however , the degree of injectate spread may be different for live patients than for cadavers.conclusionthis study helps further the understanding of injectate spread following ultrasound - guided tap injections . \n specifically , it suggests that 15 ml provides additional cranial caudal spread and may be an optimal volume of anesthesia .", "id": 507} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nspastic torticollis , also known as stiff neck or wryneck , is a condition in which the head is laterally flexed and rotated on the neck , secondary to painful spasm of the neck muscles .\nthere may be a report of the patient having slept in a draft from a fan , open window , or air conditioner .\nthe patient is generally afebrile , and if there is any history of trauma , it is of the mildest variety .\nchloroethane ( ethyl chloride ) spray is a vapocoolant applied topically in the treatment of athletic injuries .\nthe manufacturer indicates that it may be used as a counterirritant in the management of myofascial pain and muscle spasm .\nwe reviewed the literature and could find no large study on pediatric patients regarding this usage .\nwe report our experience with the use of chloroethane spray treating torticollis in 66 patients ranging in age from 1 to 16 years .\npatients presenting to the pediatric emergency service of a 600-bed inner - city hospital with the compliant of stiff neck were selected for treatment .\nan initial evaluation was performed , which included a medical and family history , a physical examination , and x - ray study of the cervical spine ( a - p , lateral , and open mouth views ) .\nthe patients were enrolled into either group 1 , usage of ethyl chloride spray , or group 2 , usage of normal spray . in the patients enrolled in group 1 ( after explaining the procedure to the parent and child and obtaining informed consent ) , the chloroethane spray bottle was held inverted 12 inches directly over the point of maximal neck tenderness .\nthe valve of the bottle was opened , allowing the liquid to leave as a fine jet stream .\nthe stream was left in contact with the skin for 4 to 5 seconds or until frosting of the skin occurred .\nthe procedure was considered successful if , after a 5-minute waiting period , the patient was able to freely and painlessly move his or her head and neck in the opposite side . for the control group , normal\nsaline is applied as a spray using a syringe with plastic catheter over the point of maximum tenderness and asked to move the neck after 5 minutes and note if patient can move the head and neck freely in the opposite side .\na total of 132 children with a mean age of 8.97 years ( range = 1 - 16 years ) presented to the emergency room with torticollis over a period of 3 years and were enrolled in the study .\nof the 132 , patients in group 1 were treated with chloroethane spray and those in group 2 were treated with normal saline spray .\nof the 66 patients treated with chloromethane spray , 63 ( 95% ) responded to the treatment as evidenced by their subsequent ability to move the head and neck freely ( see table 1 ) .\nno patients returned for additional treatment . of the patients in group 2 , who treated with normal saline spray\n, no patient responded to saline spray with ability to move the head freely in the opposite side ( see figure 1 ) .\nseries 1 : patients rxed with chloroethane spray ( 63/66 positive response and 3/66 negative response ) .\nthe torticollis was in several cases associated with a local head or neck condition , but 46.97% of the cases involved no underlying pathology ( table 2 ) .\nof the 3 treatment failures , 2 occurred in patients with neck trauma and 1 failure occurred in a patient with cystic hygroma .\nconditions associated with spastic torticollis . abbreviation : uri , upper respiratory infection . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic .\nthe z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided .\nto test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic .\nthe z statistic of 24 corresponded to a p value < .0001 , whether the test is 1-sided or 2-sided .\ntorticollis is a condition in which the head is laterally flexed and rotated on the neck due to shortening or spasm of the sternocleidomastoid muscle .\nacquired torticollis can be caused by a variety of problems including cold exposure , minor neck muscle trauma , and any inflammatory condition of the neck such as cervical lymphadenitis , or retropharyngeal abscess .\nless common causes include drug ingestion ( eg , phenothiazines ) and a variety of neurological conditions such as dystonia musculorum deformans , brain stem , or posterior fossa tumor or cyst . \nwe focus on describing chloroethane treatment for spastic torticollis caused by sternomastiod spasm that may be primary or secondary to a local inflammatory condition .\nthis form of torticollis is most often treated with warm compresses , analgesics , and muscle relaxants . \nit is thought that the relief is the result of the wrong acting as a counterirritant or a local anesthetic or by a placebo effect . \nsimilarly , a vapocoolant therapy has been described to successfully relieve acute myofascial trigger with point pain in children .\nin conclusion , from our study , for children and adolescents with spastic torticollis , chloroethane spray was more superior to normal saline in the pediatric emergency room .", "answer": "objective . a study to determine the efficacy of chloroethane spray compared to normal saline in the treatment of spastic torticollis in children and adolescents . hypothesis . \n chloroethane spray is more superior to normal saline for the treatment of spastic torticollis in children and adolescents in the pediatric emergency room . \n design . \n prospective randomized study . setting . \n urban inner - city hospital pediatric emergency department . \n methods and results . all children and adolescents ( between the ages of 1 and 16 years ) presenting to the author with the complaint of stiff neck were enrolled in the study . \n a total of 132 patients were enrolled . \n after complete evaluation to rule out cervical spine injury , a central neurological cause , patients were enrolled in the study . \n sixty - six patients were treated with chloroethane spray to the neck and the other 66 were given normal saline as placebo . \n sixty - three out of 66 patients treated with chloroethane spray achieved relief in 5 minutes as demonstrated by painless and free movement of the head and neck . \n no adverse effects were observed . \n the patients treated with placebo have no relief in 5 minutes . to test the null hypothesis that the percentages improved in the 2 groups equally , we calculated the z statistic . \n the z statistic of 24 corresponded to a p value of < .0001 , whether the test is 1-sided or 2-sided . \n chloroethane spray treatment was superior to placebo with a high statistical significance . conclusion . \n for children and adolescents with spastic torticollis chloroethane spray was more superior to normal saline in the pediatric emergency room .", "id": 508} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncombinations of dental and skeletal factors ranging from mild to severe are multiple characters of this discrepancy . the treatment protocols for class ii can vary widely according to professional ability , time of treatment , severity of malocclusion and patient compliance .\none of the recommended therapeutic approaches to class ii malocclusion in growing patients is functional jaw orthopedics for mandibular advancement .\nfixed devices for sagittal advancement of the mandible can be used in association with fixed mechanotherapy and is a recent advancement .\nthe effects of several compliance - free appliances for mandibular anterior repositioning in association with fixed appliances have been investigated .\nthe forsus ( forsus fatigue resistant device [ ffrd ] ) is a semirigid telescoping system incorporating a superelastic nickel - titanium coil spring that can be assembled chair - side .\nit is compatible with complete fixed orthodontic appliances and can be incorporated into pre - existing appliances .\nforsus ffrd attaches at the maxillary first molar and onto the mandibular archwire , distal to either the canine or first premolar bracket , creating a mesial force on the mandibular arch and a distal force on the maxillary arch . as the coil is compressed , opposing forces\nthus , the spring exerts equal and opposite forces onto the maxillary molars as well as the mandibular incisors .\nthe intrusive force on maxillary molars can decrease posterior vertical dimension , and the intrusive force on mandibular incisors will bring about their intrusion .\nthis appliance shows a greater range in activation and a less likelihood of breakage when compared to other inter arch compression springs .\nteuscher suggested that forward and downward growth of the maxilla could be altered using headgear , and the mandible could also change its growth direction to a forward and upward position with condylar adaptation .\na combination of forsus ffrd and headgear can bring about dramatic changes in the management of space deficiency and correction of class ii malocclusions .\na 13-year - old male patient reported to the author 's private clinic with a chief complaint of unerupted teeth in the upper front region and sought treatment for the same .\nextra orally patient presented with a symmetrical face , convex profile and competent lips [ figure 1 ] .\nintraoral examination revealed class ii molar relation on both sides , deep bite , ectopically erupting and blocked out maxillary canines , upper left lateral incisor was in cross bite and crowding in the mandibular anterior teeth and insufficient space for 33 . on radiographic examination , it was observed that the patient also has a deficient and backwardly placed mandible [ figure 2 ] .\npretreatment extraoral and intraoral photographs pretreatment lateral cephalogram and opg the following treatment objectives were established : \n to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandibleto correct crowding in both the arches and space management for ectopically erupting canineto achieve ideal overjet and overbiteto improve his facial appearance . \n to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandible to correct crowding in both the arches and space management for ectopically erupting canine to achieve ideal overjet and overbite to improve his facial appearance .\nthis would help to manage space for ectopically erupting canines along with open coil spring .\na fixed orthodontic appliance ( mbt 0.022 3 m unitek ) was initially bonded to the maxillary arch and 0.016 niti round arch wire was placed in the maxillary arch for the initial leveling and aligning phase [ figure 4 ] .\nheadgear therapy was started along with orthodontic strap up to distalize molars and to restrict downward and forward growth of the maxilla [ figure 3 ] .\n( a - c ) leveling and aligning with 0.016 ss and creating space for ectopic canines .\n( g - i ) finishing and detailing after sagittal correction space was created for the ectopically erupting maxillary canines using open coil niti springs , which were placed between the maxillary lateral incisors and first premolars [ figure 4 ] .\nonce sufficient space was created by headgear and open coil spring , the maxillary canines were bonded and ligated to the arch wire .\nthe ligature was activated periodically till the canines were brought into the maxillary arch . after the canines had been brought into their respective places , the maxillary arch wire was engaged into the canine brackets .\nthe lower arch was bonded 1-month after commencement of treatment and 0.016 round niti wire was placed in the mandibular arch .\nthe 016 round niti wires were then followed by the 019 025 rectangular niti wires . then\n0.019 0.025 rectangular stainless steel wires were placed in the upper and the lower arch .\nafter 9 months of commencement of treatment , forsus ffrd was placed [ figure 4 ] .\nthe total treatment time was about 18 months with satisfactory results [ figure 5 ] .\nthe molar relationship was corrected from a class ii to a class i. ideal overjet , and overbite were established [ figure 5 ] .\nthe deep bite and cross bite were corrected along with the correction of the ectopically erupted maxillary canines .\nperiodontal evaluation showed acceptable gingival contour and adequate width of keratinized attached gingival tissue around the maxillary canines .\na fixed retainer was bonded in the lower arch and a removable retainer with anterior bite plane was placed in the upper arch .\nocclusion remained stable 2 and 3 years after the orthodontic treatment [ figures 7 and 8 ] .\npost treatment photographs post treatment lateral cephalogram and opg post retention photographs after 2 years post retention photographs after 3 years\nthe following treatment objectives were established : \n to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandibleto correct crowding in both the arches and space management for ectopically erupting canineto achieve ideal overjet and overbiteto improve his facial appearance . \n to correct the skeletal and dental class ii malocclusion , which would include restriction of maxilla and advancement of mandible to correct crowding in both the arches and space management for ectopically erupting canine to achieve ideal overjet and overbite to improve his facial appearance .\nthis would help to manage space for ectopically erupting canines along with open coil spring .\na fixed orthodontic appliance ( mbt 0.022 3 m unitek ) was initially bonded to the maxillary arch and 0.016 niti round arch wire was placed in the maxillary arch for the initial leveling and aligning phase [ figure 4 ] .\nheadgear therapy was started along with orthodontic strap up to distalize molars and to restrict downward and forward growth of the maxilla [ figure 3 ] .\n( a - c ) leveling and aligning with 0.016 ss and creating space for ectopic canines .\n( g - i ) finishing and detailing after sagittal correction space was created for the ectopically erupting maxillary canines using open coil niti springs , which were placed between the maxillary lateral incisors and first premolars [ figure 4 ] .\nonce sufficient space was created by headgear and open coil spring , the maxillary canines were bonded and ligated to the arch wire . the ligature was activated periodically till the canines were brought into the maxillary arch .\nafter the canines had been brought into their respective places , the maxillary arch wire was engaged into the canine brackets .\nthe lower arch was bonded 1-month after commencement of treatment and 0.016 round niti wire was placed in the mandibular arch .\nthe 016 round niti wires were then followed by the 019 025 rectangular niti wires .\nthen 0.019 0.025 rectangular stainless steel wires were placed in the upper and the lower arch .\nafter 9 months of commencement of treatment , forsus ffrd was placed [ figure 4 ] .\nthe total treatment time was about 18 months with satisfactory results [ figure 5 ] .\nthe molar relationship was corrected from a class ii to a class i. ideal overjet , and overbite were established [ figure 5 ] .\nthe deep bite and cross bite were corrected along with the correction of the ectopically erupted maxillary canines .\nperiodontal evaluation showed acceptable gingival contour and adequate width of keratinized attached gingival tissue around the maxillary canines .\na fixed retainer was bonded in the lower arch and a removable retainer with anterior bite plane was placed in the upper arch .\nocclusion remained stable 2 and 3 years after the orthodontic treatment [ figures 7 and 8 ] .\npost treatment photographs post treatment lateral cephalogram and opg post retention photographs after 2 years post retention photographs after 3 years\noptimal timing for class ii treatment with fixed functional appliance is at the pubertal growth spurt with enhanced mandibular skeletal changes and minimal dentoalveolar compensation .\nstudies have shown that functional appliances improve the sagittal effect on the mandible by a significant overjet reduction .\nskeletal changes in functional appliances are brought about by stimulation of condylar growth as well as remodeling of fossa . besides the sagittal skeletal base improvement influencing overjet , the dentoalveolar effect on overjet is brought about by retroclination of maxillary and proclination of mandibular incisors .\nthe use of headgear not only restricts the sagittal growth of the maxilla but also moves posterior teeth backward .\nhowever , combination of extra oral and functional appliances seem to affect the sagittal intermaxillary relationship by acting mainly on the mandibular skeletal base and also having effect on dentitions .\nruf and pancherz reported that herbst and multibracket appliance combination was found to be a powerful tool for nonsurgical nonextraction treatment of class ii div 1 subjects in early and late adulthood .\nas opposed to rigid fixed functional devices , the spring of the ffrd allows flexibility in the position of the mandible .\nsince it is fixed in the patient 's mouth , the clinicians do not have to rely on a patient 's cooperation . in this case ,\nspace for the alignment of ectopically erupting canines was created partly by open coil spring and partly by molar distalization .\n( 2 ) distalization of maxillary molars . ( 3 ) correction of ectopically erupting canine ( 4 ) retrusion of maxillary incisors . ( 5 ) extrusion of posteriors . ( 6 ) intrusion of lower anteriors , ( 7 ) correction of overjet and overbite .\nthe treatment results showed a balanced facial profile , good interdigitations , improvement in maxillomandibular relationship .\nthis case report demonstrates the efficiency of the combined clinical use of headgear and forsus with fixed appliance to distalize the maxillary molar and also to advance the mandible .", "answer": "correction of class ii relationship , deep bite and ectopically erupting canines is an orthodontic challenge for the clinician . \n a 13-year - old male patient presented with class ii malocclusion , ectopically erupting canines , and cross bite with maxillary left lateral incisor . \n he was treated with a combination of headgear , forsus fatigue resistant device [ ffrd ] with fixed mechanotherapy for the management of space deficiency and correction of class ii malocclusions . \n headgear was used to distalize upper first molars and also to prevent further downward and forward growth of the maxilla . \n then forsus ffrd was used for the advancement of the mandible . \n the molar and canine relationship were corrected from a class ii to a class i. the objectives were to establish good occlusion and enable eruption of unerupted canines . \n all these objectives were achieved and remained stable .", "id": 509} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nBifunctional Catalyst Promotes Highly Enantioselective Bromolactonizations to Generate Stereogenic C\\xe2\\x80\\x93Br Bonds\n\nPaper sections:\n\nHalolactonization of unsaturated carboxylic acids is an important reaction that has been widely used in organic synthesis, especially for the preparation of molecules of biological relevance.1,2 Accordingly, the development of methods for inducing catalytic, enantioselective halolactonizations in general has become of great interest, and some notable successes have been recorded.3,4 Despite considerable effort, there remain some significant gaps in the area that arise, in part, from the propensity of iodonium and bromonium ions to undergo facile racemization via exchange with olefins prior to cyclization with an internal nucleophile.5 In particular, we are aware of no examples of catalytic, halolactonizations of unsaturated, alkyl-substituted carboxylic acids 1 (n = 1, 2; R1\u2013R3 = H, alkyl) that proceed via 5- or 6-exo modes of ring closure to give lactones 2 in which new carbon-halogen bonds are created at stereogenic centers with high enantioselectivity (eq 1);3h however, enantioselective bromolactonizations of 1 (n = 2, R1 = aryl, and R2 or R3 = alkyl) via 6-exo closures have been recently disclosed.3k The 5-exo cyclizations of unsaturated alcohols to generate stereogenic carbon-halogen bonds by haloetherification are known,6 but the products, which are cyclic ethers, are arguably less versatile as synthetic intermediates than the corresponding lactones. For example, halolactones may be readily converted into halohydrins and epoxides. Finally, we are aware of no examples of catalytic, enantioselective halolactonizations involving prochiral dienes.
In the context of several ongoing projects in natural product synthesis, we encountered a requirement to induce the enantioselective bromolactonizations of a number of structurally different alkenes. We thus sought to address the existing problems in the field with a novel approach to bifunctional catalyst design.7 Mechanistic considerations suggest that a Lewis base can mediate proton transfer and/or stabilize the intermediate bromonium ion,5c and a Lewis or Br\u00f8nsted acid can activate the brominating agent.4b These catalytic elements must then be incorporated on a suitable chiral scaffold. There are a number of possibilities, but we decided to use the binaphthyl backbone, which has been widely used as a chiral template for catalyst design.8 Although BINOL-derived catalysts have been used to promote enantioselective iodo\u2013diene cyclizations 9 and haloetherifications,6 binaphthyl-derived ligands do not appear to have been used in halolactonizations. Accordingly, we envisioned that 5, employing a bifunctional partnership of an amidine moiety3e,k and a phenolic \u2013OH group,10 might be an effective catalyst. Bulky groups at the 3- and/or 3\u2032-position of binaphthyl ligands can enhance stereoselectivity, so a 3-phenyl group was incorporated in the first generation catalyst. Catalyst 5 can be readily made on multigram scale in seven steps and 41% overall yield from commercially available material. Monotriflation of 3-phenyl-BINOL (3), which was prepared by the protocol of Shi,11 followed by nickel(0)-catalyzed cyanation provided 4 in 78% yield (2-steps). Reduction of nitrile 4 to the amine and subsequent amidine formation delivered the catalyst 5 in 71% yield (2-steps) (Scheme 1).
The validity of this new catalyst design was quickly confirmed in preliminary experiments. At the low temperatures required to minimize the background reaction, the commonly used \"Br+\" sources N-bromosuccinimide (NBS) and N,N\u2032-dibromodimethyl hydantoin (DBDMH) gave only trace amounts of product. However, we found that bromolactonizations of a series of 5-alkyl-4(Z)-pentenoic acids 6a\u2013e using 2,4,4,6-tetrabromocyclohexadienone (TBCO) (1.2 equiv) as the brominating agent and 10 mol % of the catalyst 5 proceeded with high regioselectivity to deliver the corresponding \u03b3-lactones 7a\u2013e in excellent yields (eq 2), with enantiomeric ratios (er) between 95:5 \u2013 98:2 for branched alkyl substrates 6b\u2013e and 85:15 for the n-alkyl substrate 6a (Table 1, entries a\u2013e).12 The observation that TBCO is superior to NBS and DBDMH is surprising as in other reports TBCO has been shown to be less efficacious than NBS and DBDMH as a source of electrophilic bromine. 3h,j
These reactions represent the first examples of catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via a 5-exo mode of ring closure to give products in which stereogenic carbon\u2013bromine bonds have been formed with high enantioselectivity. The enantioselectivity for the bromolactonizations of Z-olefins was significantly higher than those for the corresponding E-olefins. For example, E-6c (R1 = i-Pr, R2 = H) underwent cyclization to give the diastereomer of 7c in 98% yield but in 71:29 er. Similar to the findings of Yeung,3g 5-aryl-4(E)-pentenoic acids 6f\u2013h underwent bromolactonization via a 6-endo cyclization mode to give the corresponding \u03b4-lactones 8f\u2013h in uniformly high yield and enantioselectivity (Table 1, entries f\u2013h).
Enantioselective halolactonizations of 4-aryl-4-enoic acid substrates via a 5-exo cyclization mode are well precedented (eq 3), 3b,d\u2013f and we found that 5 also catalyzes the cyclizations of 9a\u2013c in the presence of TBCO to furnish the \u03b3-lactones 10a\u2013c in high yield and er (Table 2, entries a\u2013c). The electronic nature of aryl substituents plays an important role in these reactions; greater electron withdrawing power enhances the enantioselectivity.13 When the 5-substituted-5-eneoic acids 9e,f are used as substrates, the bromolactonization proceeds via a 6-exo mode to give \u03b4-lactones 11e,f (Table 2, entries e,f).3d,e To our knowledge the exo cyclizations of 9d,f are the first examples of a catalytic, enantioselective halolactonization of a trialkyl-substituted olefinic acids to give lactones in which a stereogenic carbon- bromine bond is formed (Table 2, entries d,f), although a related bromolactonization of an aryl-substituted unsaturated acid was recently reported.3k It is noteworthy that the enantioselectivity for the 6-exo cyclization of 9f is somewhat higher than that for the 5-exo cyclization of 9d.
A major challenge to any catalytic, enantioselective transformation is its application to the desymmetrization of prochiral substrates. It is thus significant that 5 catalyzes the bromolactonization of prochiral dienoic acids as exemplified by the conversion of 12 into 13, the absolute stereochemistry of which was established by x-ray analysis, with high regioselectivity and 73:27 er (eq 4). It is noteworthy that similar bromolactonizations to give racemic products have been used as key steps in the syntheses of several naturally occurring compounds.14
The basic mechanistic features of bromonium ion-initiated cyclizations are reasonably well established.4b,5c Catalyst 5 is unusual in that it contains relatively acidic phenolic- and highly basic amidine-functions, so determining the identities of the Br\u00f8nsted acid and the Lewis base is somewhat problematic. With this caveat in mind, one tentative working model that is consistent with the stereochemical outcome of bromolactonizations catalyzed by 5 is shown in Figure 1. We assume that hydrogen bonding between the phenolic \u2013OH and the carboxyl group orients the substrate relative to the catalyst and that the substituent on the olefin is directed away from the face of the binaphthyl scaffold in a way that minimizes torsional strain within the substrate and steric interactions with the catalyst. The bromonium ion is presumably then stabilized by interaction with the amidine moiety. Our preliminary analysis suggests that the amidine may be an important stereochemical control element in these reactions, although the 3-phenyl group does appear to help by compressing the substrate toward the amidine moiety. In support of this hypothesis, we performed a test experiment and found that the norphenyl analog of 5 catalyzed the bromolactonization of 9a to give 10a with somewhat lower (81:19 er) enantioselectivity than 5 (Table 2, entry a).
In summary, we have developed 5 as a novel bifunctional catalyst to promote highly efficient and enantioselective bromolactonizations of an unusually broad array of structurally distinct, unsaturated acids. Like other known catalysts, 5 promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but unlike those catalysts, it induces the bromolactonizations of alkyl-4(Z)-pentenoic acids via 5-exo cyclizations to give lactones in which new carbon\u2013bromine bonds have been formed at stereogenic centers with high enantiomeric ratios. Bromolactonizations of trisubstituted olefinic acids that proceed via 5- and 6-exo cyclizations occur with good enantioselectivity. We also disclose the first example of the desymmetrization of a prochiral dienoic acid by a catalytic, enantioselective bromolactonization. Although the enantiomeric ratios observed for the bromolactonizations of more demanding substrates is modest, the chiral framework of 5 offers numerous opportunities for structural modification to improve enantioselectivities and to extend the utility of this class of catalysts to other electrophile-initiated cyclizations, including iodo- and chloro-lactonizations. These developments as well as the use of catalysts related to 5 in key steps in complex molecule synthesis will be reported in due course.
", "answer": "A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon\\xe2\\x80\\x93bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization.", "id": 510} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin may 2001 , 24 cases of s. typhimurium dt160 salmonellosis were reported in the auckland region compared with an average of four sporadic cases each month with this serotype in the previous 7 months .\nraw and undercooked egg consumption was commonly reported by the first 10 case - patients interviewed .\na case - control study and environmental investigation were undertaken to identify the vehicle of infection and source of the outbreak .\nrecognizing the potential for a widely dispersed foodborne outbreak , we expanded the investigation throughout new zealand .\nwe defined a case as diarrhea ( 3 loose stools in a 24-hour period ) or vomiting after april 28 , 2001 , with a stool specimen positive for s. typhimurium dt160 .\npatients were excluded if they had a history of contact with another person with culture - confirmed s. typhimurium dt160 infection , or if they had a history of recent overseas travel . each case\nwas matched with two controls found from randomly drawn telephone numbers , matching for neighborhood and age ( < 1 , 14 , 514 , > 14 years ) .\nthe questionnaire covered symptoms ( patients only ) and contact with other symptomatic persons , bird or animal contact , and food consumption in the 3-day period before onset of illness ( cases and controls ) . parents or guardians were interviewed on behalf of children ages < 12 years .\nstepwise conditional logistic regression analyses were performed , also using sas , to identify the combination of variables that best explained the differences between case - participants and controls .\nsamples from the drinking water supply of case - patients with a history of recent consumption of nonreticulated water were collected and tested for coliforms and s. enterica by using standard methods ( 6 ) .\nbrands of eggs eaten raw within the incubation period were sampled at random from retail displays at the case - patients purchase site .\neggshell surfaces and contents were tested with standard methods ( 7 ) . broken or cracked eggs were excluded from analysis .\nsalmonella isolates were serotyped by using the kauffman - white scheme ( 8) and s. typhimurium isolates were phage typed by using the laboratory of enteric pathogens method ( 9 ) . from may\nto august 2001 , a total of 170 case - patients meeting the case definition were identified . of these , 119 ( 70% )\nagreed to participate and were enrolled in the study , along with 235 matched controls .\nthe median age of case - patients was 8 years ( range 4 months to 90 years ) , and 57% were female .\nthe most frequently reported symptoms were diarrhea ( 97% ) , abdominal pain ( 77% ) , excessive tiredness ( 67% ) , and fever ( 66% ) .\nthe median duration of illness was 7 days ( range 144 days ) ; 17 ( 15% ) patients were hospitalized , and none died .\ncase - patients and controls did not differ significantly according to age , sex , immunosuppressive therapy , treatment to reduce gastric acidity , or use of antibiotics .\nall s. typhimurium dt160 isolates were sensitive to ampicillin , cephalothin , chloramphenicol , ciprofloxacin , co - trimoxazole , gentamicin , streptomycin , sulfonamides , tetracycline , and trimethoprim .\nfour represented different levels of contact with other persons with gastrointestinal illness ( i.e. , within 28 days of illness onset ; within 3 days of onset ; within the household ; or outside the household ) . direct handling of dead wild birds , consumption of fast food , and consumption of food at a large gathering , such as at a party or large barbecue , were also significantly associated with illness .\nafter stepwise regression , contact with a person with gastrointestinal illness in the 28 days before onset of illness in the case - patient ( adjusted odds ratio [ or ] 2.8 ; 95% confidence interval [ ci ] 1.4 to 5.4 ) , exposure to dead wild birds ( adjusted or 10.5 ; 95% ci 2.3 to 47.5 ) , and consumption of fast food ( adjusted or 1.7 ; 95% ci 1.0 to 2.9 ) had independent significant associations with illness .\ndt , definitive type ; d&v , diarrhea and vomiting ; or , odds ratio ; ci , confidence interval .\ntwelve case - patients throughout new zealand indicated that they had drunk water from nonreticulated and untreated water sources .\nseven patients used roof - collected rainwater , and one used rainwater plus water from a dam .\nfour of the five patients who had eaten raw eggs could identify the retail brand and outlet of purchase .\nthese four patients had purchased six different brands of eggs from seven different retail outlets .\nsamples for two brands were positive for s. thompson , both from shell surface washings .\nepidemiologic investigation of an outbreak of s. typhimurium dt160 infection in new from may to august 2001 found that contact with dead wild birds , contact with other persons with gastrointestinal illness , and consumption of fast food were all significantly associated with illness .\nin addition , s. typhimurium dt160 was found in roof - collected rainwater drunk by five patients .\ns. typhimurium dt160 had been previously identified as the cause of large numbers of sparrow deaths in new zealand in 2000 , and analysis by pulsed - field gel electrophoresis ( using the method described by barrett et al\n. and restriction enzyme xbai ) demonstrated that bird and human isolates in 2000 were indistinguishable ( 4 ) . in our study , information was not collected on exposure to environments contaminated by wild bird feces , such as parks and play areas , a fact that may have underestimated the avian contribution to human illness .\ns. typhimurium dt160 has previously been recognized as a bird pathogen in canada ( 11 ) and in england ( 12 ) . before its emergence in new zealand , the human s. typhimurium\ndt160 infection had only been reported in the context of a 1979 institutional outbreak in the united kingdom , linked to food contamination by sparrow droppings ( 13 ) .\nconsumption of undisinfected water has previously been identified as a risk factor for salmonellosis linked to bird transmission ( 14 ) .\nthis risk factor was not confirmed by our case - control study , despite the finding of s. typhimurium dt160 in roof - collected rainwater .\nthis discrepancy is probably because case - patients and controls were matched by neighborhood , and types of water sources are usually consistent within neighborhoods .\nthe association of illness with contact with another person with gastrointestinal illness is likely underestimated because secondary salmonellosis cases were excluded .\nconsumption of fast food was associated with illness ; however , no single type of food outlet or food was identified .\ncase - patients were equally likely to have eaten food from chain fast - food restaurants as from family - owned fast - food outlets .\nconsumption of fast food may have occurred in environments contaminated by bird feces , or the foods themselves may have been contaminated , either during production or by infected foodhandlers ( 15 ) .\nasymptomatic salmonella carriers would not have been excluded from selection as controls , potentially reducing the magnitude of observed associations .\nrecall may have been influenced by delays between exposure and interview , although participants were asked to refer to a memory aid ( personal diary or calendar ) .\nthe investigation successfully excluded a single common source exposure for this outbreak and instead suggested that multiple exposures contribute to s. typhimurium dt160 infections in new zealand .\nstrategies for addressing these exposures include routine treatment of roof - collected rainwater , hygienic disposal of dead birds , and promotion of hand - hygiene protocols and sick foodhandler policies in fast - food outlets .\nthe source of this incursion of s. typhimurium dt160 into new zealand remains unknown : bird isolates have been exclusively from nonmigratory birds , s. typhimurium dt160 has not been identified in neighboring countries in the pacific basin , and early case - patients did not have a history of overseas travel .", "answer": "an outbreak of human salmonella enterica serotype typhimurium dt160 infection in new zealand was investigated from may to august 2001 . \n handling of dead wild birds , contact with persons with diarrheal illness , and consumption of fast food were associated with infection . \n contaminated roof - collected rainwater was also detected .", "id": 511} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 20-year - old refugee from liberia was referred to our hospital because of a loud murmur .\n, he had been admitted to a hospital in his home country several times because of respiratory tract infections and heart\nproblems. he had a low body weight of 45 kg at a height of 1.63 m. he was hypertensive with a 50 mmhg difference in systolic blood pressure between his upper and lower extremities : 170 vs. 120 mmhg .\nthe electrocardiogram showed sinus rhythm 84 beats / min with signs of left ventricular hypertrophy .\n1 ) revealed a dilated , hypertrophied and hyperdynamic left ventricle due to a large pda with a continuous left - to - right shunt .\njust distal to the pda , narrowing of the aorta was visible , with an increased systolic flow velocity .\nthe absence of a classic sawtooth pattern in the continuous wave signal from the descending aorta as well as the presence of holodiastolic flow reversal in the abdominal aorta suggested non - severe coarctation .\nthe cardiac valves showed no abnormalities except for a mild pulmonary regurgitation with an early - diastolic flow velocity of around 3 m per second , suggestive of elevated pulmonary artery pressure .\nthe descending thoracic aortic wall had an irregular aspect and its narrowing was most severe just distal to the pda .\nright ventricular and main pulmonary artery pressures were elevated ( systolic right ventricular pressure 55 mmhg , main pulmonary artery pressure 48/31 mmhg at a systemic blood pressure of 167/84 mmhg ) , but peripheral pulmonary artery pressures were normal .\na peak - to - peak gradient of 50 mmhg was measured in the descending aorta . \n\n1transthoracic echocardiography in patient a. a apical four - chamber view showing dilated and hypertrophied left ventricle .\nb parasternal view of the pulmonary trunk and arteries showing turbulent flow due to a pda with left - to - right shunting ; a stenosis of the proximal right pulmonary artery is also visible ( asterisk ) . c suprasternal view showing pda ( asterisk ) as well as coarctation of the aorta .\nd continuous wave doppler signal from the descending aorta , showing elevated systolic flow velocity of about 4 m per second .\n2preoperative and postoperative magnetic resonance angiography . a preoperative magnetic resonance angiography ( mra ) of the aorta ( sagittal plane ) , showing large pda ( black arrow ) and irregular aspect of the descending aorta with coarctation distal to the pda ( white arrow ) .\nb repeat mra of the aorta after surgical correction of the pda , showing irregular aspect and ( mild ) residual stenosis / coarctation of the descending aorta transthoracic echocardiography in patient a. a apical four - chamber view showing dilated and hypertrophied left ventricle .\nb parasternal view of the pulmonary trunk and arteries showing turbulent flow due to a pda with left - to - right shunting ; a stenosis of the proximal right pulmonary artery is also visible ( asterisk ) . c suprasternal view showing pda ( asterisk ) as well as coarctation of the aorta .\nd continuous wave doppler signal from the descending aorta , showing elevated systolic flow velocity of about 4 m per second .\na typical sawtooth pattern is lacking preoperative and postoperative magnetic resonance angiography . a preoperative magnetic resonance angiography ( mra ) of the aorta ( sagittal plane ) , showing large pda ( black arrow ) and irregular aspect of the descending aorta with coarctation distal to the pda ( white arrow ) .\nb repeat mra of the aorta after surgical correction of the pda , showing irregular aspect and ( mild ) residual stenosis / coarctation of the descending aorta the patient was referred for surgery .\nclosure of the ductus arteriosus was performed and the pulmonary artery was reconstructed ( fig . \nafter ligation of the pda , the pressure gradient in the descending aorta had decreased from 50 to 20 mmhg and this ( mild ) residual coarctation was left untreated . whether it will need ( percutaneous ) treatment in the future remains to be seen .\nhe had previously been diagnosed with severe hypertension with a poor response to medical therapy .\napproximately eight years prior to referral to our hospital , echocardiography had already revealed left ventricular hypertrophy .\nmoreover , it showed a pda with a continuous left - to - right shunt . a murmur had never been heard . at that time\nwhen he was referred to our outpatient clinic he did not have any cardiac complaints , although his exercise capacity had gradually deteriorated over the past year .\nin addition to the pda , echocardiography now showed not only left , but also right ventricular hypertrophy and an estimated right ventricular systolic pressure of 57 mmhg .\nhe was referred for treatment of his pda on the assumption that it had contributed to the development of pulmonary hypertension .\nit must be noted that the pda was silent and did not appear very large on echocardiographic and mri .\nmoreover , diastolic dysfunction due to left ventricular hypertrophy may have played an important role in the development of pulmonary hypertension as well .\nhowever , a contribution of the pda to the development of pulmonary hypertension could not be excluded and the patient was therefore accepted for percutaneous closure of the pda .\nangiography of the aortic arch and the occluded pda with coil in situ can be seen in fig . \nin due time , echocardiography will be repeated to document whether his pulmonary artery pressure will decrease . \n\nmri visualised the jet of the pda flow entering the pulmonary bifurcation ( black arrow)fig . \nmri visualised the jet of the pda flow entering the pulmonary bifurcation ( black arrow ) angiography of the aortic arch .\npda is usually diagnosed shortly after birth , and treated surgically or percutaneously to prevent the development of pulmonary hypertension and heart failure .\nthe first case represents a more complex form of pda , associated with additional congenital cardiovascular anomalies and with left ventricular volume overload as one of its main characteristics . in the second patient ,\npulmonary hypertension was the sole reason for closure of the pda , and left ventricular dilation had not developed .\na difference in shunt size is probably the main reason for this difference . in addition\n, it may be possible that patient b s severe left ventricular hypertrophy due to hypertension prevented left ventricular dilatation .\nclosure of a pda is only feasible when irreversible pulmonary hypertension has not yet developed . in adults ,\na , surgical correction of the pda was performed because of its large size and concomitant anomalous aortic anatomy .\npda patients who are beyond surgical or percutaneous closure should be treated according to the guidelines for eisenmenger syndrome .", "answer": "patent ductus arteriosus ( pda ) is a rare diagnosis in adults , since symptoms and signs usually occur in infancy and most cases are treated shortly after diagnosis . \n we present two patients who were first diagnosed with pda during adulthood . \n the first case represents a more severe form of pda , where the need for closure of the pda is obvious . in the second case \n the sequelae of the pda are less clear . in both \n patients , closure of the pda ( surgically in one case , percutaneously in the other ) was successful .", "id": 512} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprocalcitonin ( pct ) is a 14-kd protein encoded by the calc-1 gene and synthesized physiologically by thyroid c - cells . under normal conditions , serum pct levels are negligible .\nafter shock or tissue injury ( i.e. burn , trauma , surgery ) or infections and sepsis , pct mrna expression has been documented in human extra - thyroidal tissues .\nthus , systemic pct concentrations are considered as a component of the inflammatory response and as an acute - phase marker . in cardiac acute patients , data on pct\nsome studies [ 3 , 4 ] reported that pct levels were increased in acs patients on admission , whereas other investigations [ 5 , 6 ] documented that plasma pct concentrations were in the normal range in patients with uncomplicated acute myocardial infarction .\nelevated concentrations of pct have been reported in patients with cardiogenic shock . in a more recent retrospective study , it was observed that cs patients showed high pct concentrations , especially in the presence of multiorgan failure ( mof ) and in absence of signs of infections ( cultures and clinical findings ) .\nwe recently observed that the degree of myocardial ischemia ( clinically indicated by the whole spectrum of acs , from unstable angina to cardiogenic shock st - elevation following myocardial infarction ) and the related inflammatory - induced response are better reflected by crp ( which was positive in most acute cardiac care patients of all our subgroups ) than by pct which seems more sensible to a higher extent of inflammatory activation , being positive only in all cs patients . in these patients , the clinical interpretation of absolute pct values ( both in diagnostic and prognostic terms ) , represent a major challenge since they may be influenced by several factors , such as the degree of systemic inflammatory response , the coexistence of multiorgan dysfunction , the presence / absence of infections and finally by the time of measurements during hospital course ( i.e. the dynamics of pct levels ) .\nno data are so far available on the dynamics of pct levels in patients with cardiogenic shock .\nthe aim of this preliminary investigation was therefore to evaluate the serum evolution of pct during intensive cardiac care unit ( iccu ) staying in a group of patients with cardiogenic shock ( cs ) following st - elevation myocardial infarction ( stemi ) submitted to primary percutaneous intervention ( pci ) with no laboratory or clinical sign of infection .\nten consecutive patients with cardiogenic shock following stemi were submitted to pci and then admitted to our 12-bed iccu in florence , a tertiary center , from 1 september 2008 to 31th march 2009 . to be eligible for the present study , all patients had to be free of infection at the time of blood sampling , as evidenced by both clinical and microbiological examinations , including urinary cultures and microbiological examinations of tracheal aspirate in mechanical ventilated patients and blood cultures . a clinical diagnosis of cardiogenic shock was made if all the following criteria were present : 1 .\nsystolic blood pressure persistently less than 90 mmhg or vasopressors required to maintain a systolic blood pressure of more than 90 mmhg ; 2 .\nsigns of hypoperfusion ( e.g. urine output less than 30 ml / hour or cold / diaphoretic extremities or altered mental status ) ; 3 .\nclinical evidence of elevated left ventricular filling pressure ( e.g. pulmonary congestion on physical examination or chest x - ray ) .\npulmonary artery catheterization was not required when all clinical criteria and echocardiographic evidence of left ventricular dysfunction without mechanical complications were present .\nthe day after iccu admission blood samples were obtained for cardiac biomarkers ( tni < 0.15 ng / ml ) , leucocytes count ( 4000 - 10000/l ) , crp ( < 9 mg / dl ) , uric acid ( < 6.5 mg / dl ) , nt - pro brain natriuretic peptide ( nt - probnp , in males 0 - 50 yrs : < 88 pg / ml , > 50 yrs : < 227 pg / ml ; in females : 0 -50 yrs : < 153 pg / ml ; > 50 yrs : < 334 pg / ml ) and procalcitonin measurements ( normal values < 0.5 ng / ml ) .\ntransthoracic 2-dimensional echocardiography was performed on admission in order to evaluate left ventricular ejection fraction ( lvef ) .\napache ii ( acute physiology and chronic health evaluation ii ) score was also assessed .\nthe study design was approved by the local ethic committee and inform written consent was obtained for each patient .\nstatistical analysis was performed by means of spss 13.0 package ( spss inc , chicago , il ) .\ndata are reported as frequencies and percentages or means s.d . and analyzed with fisher s exact test and student s t test , respectively .\nsince pct was determined once a day , its mean value for each day of hospital stay in either group of patients has been calculated and graphically plotted in order to obtain two linear regression lines , whose slopes have been subsequently compared by means of an f test . in all analyses ,\ntable 1 shows the clinical characteristics of cs patients following stemi included in the study after pci .\nclinical characteristics of patients included in the study . compared with survivors , dead patients exhibited higher values of apache ii score , as well as trend towards higher serum concentrations of troponin i , though it did not reach statistical significance .\nno significant differences were detectable in regard to age , sex , infarct location , left ventricular ejection fraction , and mean arterial pressure between the two subgroups . \nas depicted in table 2 , higher values of glycemia , nt - probnp and crp were detectable in dead patients in respect to survivors .\nbasal serum concentrations of procalcitonin were higher in ( dead ) survivors patients , though this difference did not reach statistical significance due to high values of standard deviation .\nas depicted in figure 1 , the pattern of pct variations during iccu course was significantly different in cs patients who survived in respect to those who died ( survivors : slope = -3.760.71 standard error ; dead : slope = -0.810.35 standard error , p=0.004 ) .\nthe main finding of the present investigation , though preliminary and performed in a small subset of patients , is that the patterns of temporal pct variations throughout iccu course were heterogeneous in patients with cs and no clinical or laboratory signs of infection .\na progressive reduction in pct values was observed in cs patients who survived , whereas the lack of changes in pct concentrations was documented in cs patients who died .\nconversely , basal absolute pct values were not significantly different between the two subgroups , since they exhibit a wide range of values in the overall population .\nsponholz et al . described the evolution of serum procalcitonin levels after uncomplicated cardiac surgery and observed a progressive return to normal levels within the first week .\npeak pct levels were reached within 24 hours postoperatively and this increase seemed to be dependent on the surgical procedure , being more invasive procedures associated with higher pct levels , and on intraoperative events , including aortic cross - clamping time , duration of cardiopulmonary bypass and duration of surgery . in infected patients , pct levels were elevated throughout the first week postoperatively [ 19 , 20 , 21 ] , with a more pronounced trend in bacterial and fungal infections than in viral infections of sirs . [ 22 , 23 ] .\nthe authors concluded that the dynamics of pct levels , rather than absolute values , may be more important for identifying patients with infectious complications after cardiac surgery .\nmore recently prat et al . confirmed a slight increase in pct values in the first postoperative day after cardiac surgery , in agreement with previous results [ 25 , 26 , 27 ] and with adamik et al .\n, who showed that the development of postoperative complications after cardiac surgery with cardiopulmonary bypass was associated with increased postoperative neopterin and pct levels .\nsimilarly , after heart transplantation , serum pct levels display a rise in response to surgery , with a peak on day two , whereas high peak levels with delayed return to normal values should lead to a search for inflammatory processes , as they are often associated with increased morbidity and mortality . \nlikewise , in patients with cardiogenic shock and no sign of infections we documented a reduction of pct levels only in survivors cs patients .\nthis time course of procalcitonin can probably be explained , both in postsurgical and in cs patients , by normal pct kinetic . in healthy subjects\nthe injection of endotoxin is followed by a rise in pct , reaching a maximum 24 hours thereafter . \nthe return of pct levels to normality within a few days in surgical patients ( after an uncomplicated postoperative course ) and in cs survivors patients can be explained by half - life of pct ( 18 to 24 hours ) , in absence of a further insult that might induce pct production .\nour findings , along with those in cardiac surgery strongly support the contention that the dynamic \napproach may be more reliable that the static one ( that is the absolute single pct value ) especially in the challenging conditions characterized by a systemic inflammatory response , such as cardiac surgery and cardiogenic shock . indeed , in a cohort of unselected critically ill patients , jensen et al . \nobserved that a pct increase was an independent predictor of 90-day survival and that the pct day - by - day changes was able to identify critically ill patients at a higher risk of icu mortality . on the other hand ,\nthe initial ct level did not predict mortality , even though many patients were admitted with a pct 1.0 ng / ml .\nthis suggests that several pct measurements should be made consecutively to assess the critically ill patient s infection - related mortality risk ( to monitor treatment of infection day - by - day ) . in our investigation\nwe further confirmed that higher values of nt - probnp are associated with increased mortality in cs patients and that a more marked systemic inflammation ( as inferred by higher values of crp ) and higher severity score ( as indicated by apache ii ) were associated with an ominous prognosis .\nthe main limitation of the present investigation is represented by the small number of patients . however , the population is homogeneous , comprising patients with cardiogenic shock following stemi all submitted to pci , with no clinical and laboratory sign of infections .\nit is interesting to note that , despite the small number of subjects , the behavior of pct was clearly detectable .\naccording to our preliminary findings , patterns of temporal pct variations throughout iccu course were heterogeneous in patients with cs following stemi submitted to pci and no clinical or laboratory signs of infection .\na progressive reduction in pct values was observed in cs patients who survived , whereas a lack of changes in pct concentrations was documented in cs patients who died .\nour findings strongly support the contention that the dynamic approach may be more reliable that the static one ( that is the absolute single pct value ) especially in the challenging conditions characterized by a systemic inflammatory response , such as cardiogenic shock .\nwe further confirmed that higher values of nt - probnp are associated with increased mortality in cs patients and that a more marked systemic inflammation ( as inferred by higher values of crp ) and higher severity score ( as indicated by apache ii ) were associated with an ominous prognosis .", "answer": "introductionprocalcitonin concentrations are considered as a component of the inflammatory response and as an acute - phase marker , after shock or tissue injury ( i.e. burn , trauma , surgery ) or infections and sepsis . \n no data are so far available on the dynamics of procalcitonin levels in patients with cardiogenic shock following st - elevation myocardial infarction , with no clinical or laboratory sign of infection.methodswe evaluated procalcitonin values every day during intensive cardiac care staying in ten cardiogenic shock patients admitted to our intensive cardiac care unit . nt - pro brain natriuretic peptide , c reactive protein and apache ii score were also assessed.resultssix patients survived , whereas 4 patients died . \n a progressive reduction in procalcitonin values was observed in cardiogenic shock patients who survived , whereas the lack of changes in procalcitonin concentrations was documented in cardiogenic shock patients who died ( survivors : slope = -3.76 ; dead : slope = -0.81 , p=0.004 ) . \n furthermore , higher values of glycemia , nt - pro brain natriuretic peptide and c reactive protein ( as well as higher apache ii scores ) were detectable in dead patients in respect to survivors.conclusionsin our preliminary study we observed that in patients with cardiogenic shock and no sign of infections a reduction of procalcitonin levels was detectable only in survivors . moreover , higher values of nt- brain natriuretic peptide , a marked systemic inflammation ( higher values of c reactive protein ) and higher severity score ( as depicted by apache ii ) are associated with an ominous prognosis in cardiogenic shock patients .", "id": 513} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntechnetium-99 m ( tc-99 m ) in complex with methylene - diphosphonate ( mdp ) is a commonly used substrate in radionuclide bone imaging .\nbone scans utilizing this radiotracer are very sensitive and enable nuclear medicine physicians to screen for various osseous abnormalities and pathologies .\nlocalization of the radiotracer is accomplished through the exchange of tc-99 m mdp for phosphate compounds during active bone remodeling , and aggregation is subsequently detected using a gamma camera . even though the utilization of tc-99 m mdp bone scintigraphy is useful for identifying various physiologic abnormalities , its overall specificity is limited primarily by the lack of anatomic detail .\nit is therefore important to utilize the patient 's medical history , in conjunction with other forms of imaging , to aid in differentiating potential pathologies . here ,\nwe present a case in which tc-99 m mdp bone scintigraphy was utilized to raise concern for a serious abnormality despite relatively occult findings by conventional imaging modalities .\na 70-year - old male presented with mild left hip pain and was found to have an elevated serum alkaline phosphatase ( alk ) level of 770 units / l .\nunfortunately , due to a language barrier , a complete medical history could not be obtained . in light of the patient 's elevated alk level ,\nthe planar whole body images [ figure 1a ] of the tc-99 m mdp bone scan demonstrated intense diffuse uptake extending from the left femoral head to the proximal shaft of the femur .\ninitially , we felt this type of appearance could be compatible with early paget 's disease given the markedly elevated alk , despite the absence of apparent structural deformities .\n70-year - old male with mild left hip pain and elevated alkaline phosphatase diagnosed with radiogenic osteosarcoma .\n( a ) the planar whole body images of the technetium-99 m methylene diphosphonate bone scan demonstrates intense diffuse uptake extending from the left femoral head to the proximal shaft of the femur ( double ended arrow ) .\n( b ) the plain film of the left hip depicts three previously unreported fixation screws surrounded by osteopenic lesions ( arrow ) in the femoral neck and head . to confirm the initial diagnosis ,\nthe patient was sent directly for an x - ray [ figure 1b ] . however , the pattern of multifocal sclerosis ( cotton wool appearance ) that would be expected of paget 's disease was not present . instead , the radiograph demonstrated three previously unreported fixation screws , used to repair a femoral neck fracture ( later discovered to have occurred 1 year ago ) . surrounding the screws were poorly defined osteopenic , potentially lytic lesions in the femoral neck and femoral head [ figure 1b ] .\ncorrelation of the tc-99 m mdp bone scan with the x - ray changed the initial diagnosis from suspected paget 's disease to a differential of malignancy / metastasis , reparative phase of osteonecrosis , osteomyelitis , or reactive osteolysis to the fixation screws . though simple loosening of the fixation screws could have explained the patient 's mild hip pain , the activity demonstrated by the bone scan was much too diffuse and intense to support this diagnosis . to evaluate for metastatic disease ,\na computed tomography scan of the chest , abdomen , and pelvis was ordered the following day .\nevaluation of the scan of the left hip was limited due to streak artifact from the screws ; however , it was still possible to appreciate some mixed lytic / sclerotic changes in the native bone [ figure 2a and b ] .\neven though these changes raised the suspicion of osseous malignancy or metastasis , they were not pathognomonic , as hardware loosening , osteopenia , and degenerative changes could have a similar appearance .\nhowever these findings in combination with the bone scan findings , provided enough suspicion of a pathology sinister enough to refer the patient for surgical hardware revision with potential biopsy .\n70-year - old male with mild left hip pain and elevated alkaline phosphatase diagnosed with radiogenic osteosarcoma .\n( a and b ) computed tomography of the pelvis reveal mixed lytic / sclerotic lesions ( arrows ) within the native bone , although evaluation of the left hip was limited due to streak artifact as seen on the two axial slices in figure 1 .\nsurgical exploration of the left hip revealed a grossly abnormal appearance of the left proximal femur with areas of hemorrhagic bone surrounding lytic lesions .\nhistologic study of the biopsy [ figure 3 ] demonstrated sarcomatous , spindle shaped cells with adjacent tumor osteoid production ; represented by eosinophilic , amorphous , fibrillary deposits between individual or small aggregates of tumor cells .\n70-year - old male with mild left hip pain and elevated alkaline phosphatase diagnosed with radiogenic osteosarcoma .\nhistologic examination of the curettage ( using hematoxylin and eosin stain , 10 ) reveals sarcomatous , spindle shaped cells ( white arrows ) with adjacent tumor osteoid production ( black arrows ) ; represented by eosinophilic , amorphous , fibrillary deposits ( white arrows ) between individual or small aggregates of tumor cells ( black arrows ) . in context , the presence of osteosarcoma was highly unlikely as there have been no case reports of primary osteosarcomas occurring in a site of a fracture that was surgically repaired 1 year prior .\nadditionally , the distal femur would be a far more likely site for a primary osteogenic sarcoma to occur .\nhowever , upon further interrogation of the patient 's past medical history , it was discovered that the patient had prostate cancer 11 years ago .\ngiven the standard of care at that time , one could surmise that he was treated with 60 - 70 gy of targeted external beam radiation to the prostate .\nthe dose that he received and the time frame since receiving his radiation would be compatible with radiogenic osteosarcoma as there is a latency period of about 10 years .\nthe repaired stress fracture 1 year prior was potentially pathologic from the malignancy , but was most likely missed due to the slightly atypical radiographic appearance on the plain film x - ray performed in the surgeon 's office .\ntc-99 m mdp bone scans are very sensitive tests for detecting a wide array of abnormalities within the bone . despite its comprehensive applicability ,\nit is limited in identifying specific diseases and pathologies ; often relying on the addition of other investigative modalities to reach a final diagnosis . here , a tc-99 m mdp bone scan was used to identify the presence of abnormal bone remodeling , which led to further imaging work - up and confirmatory biopsy .\nosteosarcomas are particularly sensitive to tc-99 m mdp bone scans as their pathology involves active bone remodeling .\nhowever , its presence here was unexpected due to the atypical location on the bone scan and the limited available medical history ( due to a language barrier ) . when paired with the patient 's medical history of radiation treatment and recent fracture ,\nthe femur would have been exposed to scatter and bremsstrahlung radiation from its proximity to the treatment field . additionally , the 10-year latency period to developing malignancy is typical for post - external beam radiation therapy induced malignancies .\nthe tc-99 m mdp bone scan demonstrated its value by raising the suspicion for a more sinister process in the left hip than was seen in radiographic appearance on plain film .\nthis case demonstrated the value of tc-99 m mdp bone scintigraphy as an initial detector of bone abnormalities .\nits sensitivity prevents it from identifying specific pathologies without the aid other investigative methods as depicted in this case .\nthis case also underscores the importance of considering the bone scan findings in conjunction with the patient 's clinical history and anatomic imaging . by using all this information in combination\n, we were able to sift through the differential and refer the patient for appropriate management .", "answer": "we present a case of a 70-year - old male who was referred for a technetium-99 m methylene - diphosphonate bone scan for mild left hip pain and an elevated alkaline phosphatase level of 770 units / l . \n no additional information was provided and the patient 's history was limited due to a language barrier . \n we were able to ascertain that the patient had a remote history of prostate cancer , which had been treated with radiation . \n originally , we felt the bone scan was compatible with paget 's disease ; however , further work - up revealed the presence of osteosarcoma , which was potentially radiation - induced .", "id": 514} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npreoperative anxiety or stress have been thought to delay gastric emptying and increase gastric acidity and is therefore considered one of risk factors related with aspiration pneumonitis . in large series of olsson\net al . ( 1 ) , it was reported that pain and anxiety were able to be important mechanisms of decreasing intestinal motility especially in emergency surgical cases .\nsimilarly , outpatients tend to have increased gastric fluid , presumably because of anxiety ( 2 ) .\ncote et al . ( 3 ) found that more anxious children had a higher gastric acid content , although the difference was of questionable clinical significance .\nmore recently , clinical studies using various methods , however , have failed to confirm any correlation between anxiety and gastric function ( 4 - 6 ) .\nthe purpose of this study was to clarify whether anxiety affects the preoperative actual acidity and volume of gastric fluid with several contributing factors such as sex , age , fasting time , hypoglycemic status controlled in female patients undergoing elective gynecologic surgery under general anesthesia .\nafter obtaining an approval from the committee of ethics on human study in our hospital and an informed consent from each patient , we studied asa physical status i - ii 96 female patients aged between 16 and 60 yr who underwent elective gynecological surgery under general anesthesia .\npatients with a history of any gastrointestinal disorder , or who were receiving antacids or h2 receptor blockers , or any other medication , which would interfere with gastrointestinal function , were excluded from the study .\na power analysis was performed to determine the sufficient sample size required to establish a significant difference in the gastric variables and in the percentage of patients at risk for aspiration pneumonia based on the results of a preliminary study , using an -value of 0.05 , and power of 0.8 .\n, patients were asked to complete the visual analogue scale with regard to the level of anxiety ( range 0=no anxiety at all , to 10=extremely anxious ) in the preoperative preparing unit .\nthe patient 's data including vital signs , oral fasting time , and medical and surgical history were collected from interview and the medical records .\nimmediately after tracheal intubation using 100 - 120 mg of propofol and 0.5 mg / kg of rocuronium , a 14-f multiorifice nasogastric tube ( levin tube , yushin medical , shiheung , korea ) was inserted upto 60 cm from the incisor . proper position of the nasogastric tube was verified by auscultation over the epigastrium by injecting 10 ml of air .\nsubsequently , the gastric fluid was aspirated gently to a syringe using mild negative pressure .\nthis maneuver was repeated in both slightly left- and rightward tilted positions and in trendelenburg and reverse trendelenburg position to ensure maximum emptying of the stomach .\na standard general anesthesia with enflurane in nitrous oxide , oxygen , and rocuronium was provided for the surgery .\nthe volume of gastric fluid and ph were measured using a metered cylinder and a ph meter twice ( model-920a , orion research inc .\nblood concentration of glucose was measured at the same time by using a blood glucose meter ( surestep , lifescan inc . , milpitas , ca , u.s.a . ) .\nblood samples taken from the arm opposite to the intravenous infusion were collected and centrifuged ; the serum was separated and stored at -70. double antibody gastrin method is a radioimmunoassay technique for gastrin designed for the quantitative measurement of gastrin in serum , which utilizes labeled synthetic iodinated human gastrin ( shg i-17 ) ( 7 ) .\nvisual analogue scale ( vas ) of preoperative anxiety was 3.822.1 and the range was from 0 to 8.5 .\nwe classified the subjects into 2 groups , those presenting vas less than 5 ( low - anxiety group , l - group ) , and remains ( high - anxiety group , h - group ) .\nstatistical analysis was performed by paired t - test with bonferroni correction for demographic data .\nthe mann - whitney u - test and chi - square test were used to analyze the anxiety scores , gastric ph and volume of the gastric fluid , serum gastrin concentrations , and the number of patients at risk for aspiration pneumonitis ( gastric ph < 2.5 and volume > 25 ml ) in order to compare both groups .\nspearman 's correlation coefficient was used to measure the association between anxiety and gastric residues .\nthe two groups were comparable with regard to age , weight , height , diagnosis , fasting time , and preoperative blood glucose level .\npreoperative heart rate , systolic and diastolic blood pressures were similar in the both groups ( table 1 ) .\nthe preoperative anxiety score ( vas ) of l - group was 2.41.4 , and that of h - group was 6.00.9 .\nthe mean gastric acidity and volume of the two groups were not statistically different : ph of l - group , 3.01.8 ( range : 1.3 - 7.3 ) , ph of h - group , 3.02.0 ( range : 1.3 - 7.8 ) , volume of l - group , 15.311.7 ml ( range : 0 - 50 ) , and volume of h - group , 11.811.8 ml ( range : 0 - 70 ) .\nthere were 9 ( 15.3% ) patients considered to be ' at risk : gastric ph < 2.5 and volume > 25 ml ' in the l - group , and 1 ( 2.7% ) in the h - group ( p<0.05 , fig .\nthe mean serum gastrin concentration in the l - group was 21.69.8 pg / ml , and that in the h - group was 20.211.0 pg / ml ( p = ns ) .\nthe ph and volume of preoperative gastric contents were not significantly associated with the preoperative anxiety ( fig .\n, there were no epistaxes , vomiting , ventilatory problem , or other serious complications .\nthe main finding of this study was that there are no differences in preoperative gastric ph and volume between the two groups , but there are more patients ' at risk ' for aspiration pneumonitis in the low anxiety group .\nseveral authors reported that preoperative anxiety did not prolong gastric emptying nor had influence gastric acidity and volumes in adults and children ( 3 - 5 , 8 , 9 ) .\n( 6 ) evaluated the relationship between oral premedication , preoperative anxiety , and gastric contents in patients having elective surgery .\ngastric volume and ph did not correlate with the type of premedication or the level of anxiety .\n( 9 ) observed that a smaller gastric fluid volume in highly anxious pediatric patients compared to children with low anxiety level .\nin addition , the increased sympathetic tone disturbs gastric secretion through the adrenergic neurons in the splanchnic nerve . in our results , however , we could not detect any differences in serum gastrin concentration which has been known as a major hormone regulating secretion of gastric juice .\ninterestingly , we also observed that the number of ' patients at risk : gastric ph < 2.5 and volume > 25 ml ' was much greater in less anxious patients .\nthe smaller gastric volume of highly anxious patients was consistent with the report of kawana et al .\ntherefore , perhaps gastric motility , not gastric secretion , was altered by neural or endocrine mechanisms in the anxious patients .\ntraditionally , the -adrenergic system has been shown to exert an inhibitory action on gastric emptying in normal circumstances ; isoprenaline decreases and propranolol increases stomach emptying ( 10 , 11 ) .\nin contrast , christensen and stadil ( 12 ) reported that corticosteroids and adrenaline , in physiological concentrations , increase the acidity of gastric secretions .\nwe did not measure hormones including epinephrine , norepinephrine , or any other stress hormones .\nalthough our results did not support any association between the level of preoperative anxiety and gastric volume and ph , preoperative anxiety seems to decrease the risk of aspiration pneumonitis .\nfurther studies are necessary to clarify neurogenic and endocrine regulatory mechanisms of anxiety on preoperative gastric function . since gastric secretion and movements\nare controlled by a very complicated mechanism and gastric residuals are affected by many factors , a well controlled study design is difficult to create .\nwe tried to minimize other influencing factors for gastric secretion and emptying such as sex , age , fasting time , preoperative blood glucose concentration , and premedication .\nno attempt was made to take account of the phase of menstrual cycle or circadian variation because the effect of both has been shown not to apply to gastric emptying of liquids ( 13 , 14 ) .\nthis may be due to environmental factors including unpredictable delay of the operation , or protocol violation by the patient such as skipping the previous evening meal due to preoperative anxiety and tension .\nthe technique of gastric aspiration can not guarantee complete gastric emptying , and volumes recorded reflect only the maximum gastric aspirate obtained at the time , with every effort made to increase yield by manipulation of the tube .\ndye absorption technique and fiberoptic gastroscopy are more reliable than blind aspiration ( 15 ) , but are more complicated , time consuming , and clinically limited methods .\nwe evaluated the patients ' anxiety in terms of vas based on the study of kindler et al .\nthey reported that the vas allows effective measurement of preoperative anxiety and detection of patients ' anesthetic concerns .\nwe conclude from the current data that there are no significant differences of preoperative gastric ph and volumes between high and low anxious patients .\nhowever , the number of patients ' at risk ' for aspiration pneumonitis was much more in low anxious patients .\nthe results suggest that a low level of preoperative anxiety can be considered a risk factor in connection with aspiration pneumonitis .", "answer": "the aim of this study was to evaluate the effect of preoperative anxiety on the gastric ph and volume . \n we studied 96 female patients aged 16 - 60 yr who underwent elective gynecological surgery . \n we classified the subjects into 2 groups , those presenting preoperative anxiety scores using visual analogue scale ( vas , 0 - 10 ) less than 5 ( l - group , n=59 ) , and those with 5 and more ( h - group , n=37 ) . \n immediately after tracheal intubation , gastric contents were aspirated using a 14-f multiorifice nasogastric tube . \n the gastric acidity and volume of the two groups were not statistically different . \n mean ph were 3.01.8 and 3.02.0 in each group ( l - group and h - group ) and mean gastric volume ( ml ) were 15.311.7 and 11.811.8 , respectively . \n nine ( 15.3% ) patients in the l - group were considered to be ' at risk i.e. gastric ph < 2.5 and volume > 25 ml ' and one patient ( 2.7% ) in the h - group ( p<0.05 ) . the mean serum gastrin concentrations in both groups were similar ( 21.69.8 vs. 20.211.0 pg / ml ) . \n the ph and volume of preoperative gastric contents were not correlated with the preoperative anxiety . \n the results suggest that a low level of preoperative anxiety can be considered a risk factor for aspiration pneumonitis .", "id": 515} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmouth opening is a clinical parameter , which we encounter routinely in our daily practice .\na known normal range of mouth opening is necessary to enable the clinician conduct a thorough oral examination conveniently\n. a reduced mouth opening capacity ( moc ) may be one of the first clinical signs of pathological changes and traumatic conditions in the masticatory system .\nearly recognition of decreased or limited mouth opening is necessary for a prompt and efficient approach to diagnosis and to plan out the treatment options judiciously . to make a diagnosis of decreased mmo , it is essential to establish what constitutes the normal mmo for children of different age .\nresearch has shown that the measurement of mouth opening varies significantly with age , gender , and race .\nnumerous studies across the world have characterized the mmo in their adult as well as pediatric population .\nhowever , very little data exist on normal mmo in the indian pediatric population . in a growing population ,\nfurthermore , most existing datasets are of limited value because they do not cover the entire age range . despite these limitations ,\nthe existing normal values indicate a significance of growth on the mmo and a wide range of normalcy within a certain age category . in india , it is fairly common to report the mouth opening in terms of finger breath in our daily practice .\nunderstandably , this is semi - quantitative measurement subject to many variations . hence , establishing numerical value will be of significant value\n. the present study aims to establish age- and height - related percentiles for the mmo of healthy children and adolescents which may serve as a basis for various studies and will have the clinical utility in treatment and diagnosis of diseases directly or indirectly affecting the mouth opening .\nthe present study was carried out in the pediatric outpatient clinic in a tertiary care center in western india .\na total of 985 children , 560 males and 425 females , in the age range of 518 years were studied .\nthe children were asked to open their mouth maximally unassisted till no further opening was possible .\nmmo was measured when the children rested their heads against a firm wall surface in an upright position .\nthe distance from the incisal edge of the upper incisor teeth to the incisal edge of the lower incisor teeth was measured using a calibrated fiber ruler , and the findings were recorded in millimeters [ figure 1 ] .\nthree readings were recorded for each individual , and their average was recorded as the final reading . to control for inter - examiner and intra - examiner reliability ,\nthe age , sex , height , and weight of all the children were recorded .\nmethod of measuring interincisal distance with fiber ruler the study included all the children between the ages of 518 years of age attending pediatric outpatient clinic , having all the incisors and able to understand and cooperate with the investigators .\nexclusion criteria for the study were children with ( 1 ) habit of smoking , tobacco , or betel nut chewing , ( 2 ) no natural front teeth , ( 3 ) previous maxillofacial trauma , ( 4 ) oral malignancies , ( 5 ) angular cheilosis or oral ulcers affecting mouth opening , ( 6 ) chronic systemic disease , and ( 7 ) pain while opening mouth .\nthis study was approved by the research ethics committee of the institute . as children involved in the study were minors ,\nweight and height for each child were obtained using a standard calibrated anthropometric scale , with precision of 100 g and 1 mm , respectively .\nmean mmo values were analyzed according to age , height , and weight ranges , which were established appropriately for statistical analysis .\nhence , the sample was divided according to age and height : 13 age groups ( between 5 and 18 years ) and 10 height groups of 10 cm each ( 8695 cm ; 96105 cm ; 106115 cm ; 116125 cm ; 126135 cm ; 136145 cm ; 146155 cm ; 156165 cm ; 166175 cm ; 176185 cm ) were assigned .\ncontinuous variables are reported as mean standard deviation . to determine correlation of mouth opening with age and height ,\na linear regression analysis was performed and statistical significance was tested by the application of t - test and f - test .\nthe statistical analysis has been performed using open source software r version 3.0.1 . of r foundation , vienna , austria .\nmean mmo values were analyzed according to age , height , and weight ranges , which were established appropriately for statistical analysis .\nhence , the sample was divided according to age and height : 13 age groups ( between 5 and 18 years ) and 10 height groups of 10 cm each ( 8695 cm ; 96105 cm ; 106115 cm ; 116125 cm ; 126135 cm ; 136145 cm ; 146155 cm ; 156165 cm ; 166175 cm ; 176185 cm ) were assigned .\ncontinuous variables are reported as mean standard deviation . to determine correlation of mouth opening with age and height ,\na linear regression analysis was performed and statistical significance was tested by the application of t - test and f - test .\nthe statistical analysis has been performed using open source software r version 3.0.1 . of r foundation , vienna , austria .\nour study included a total of 985 children with 560 males and 425 females among them .\nthe median age for the entire sample is 10.5 years , and median height was 130 cm for girls and 130139.99 cm for boys .\nthe mean mmo was 43.5 5.19 for girls and 44.24 5.84 cm for boys .\ntable 1 presents the number of children in each age group with mean moc values ( mm ) for indian children .\ntable 2 presents the mean moc values ( mm ) for the indian children in each height group .\nthe scattered diagram relation of moc with age and height was plotted [ figure 2a and b ] .\nnumber of individuals in each age group for boys and girls with mouth opening capacity values ( mm ) variation in mouth opening with height ( a and b ) the scattered diagram showing relation of mouth opening capacity with age and height diagrammatic representation of mean mouth opening capacity value according to the height there was a significant difference between the moc of male and female in all age groups .\na linear relationship was observed between the mouth opening and age but more significantly with height in entire sample , with correlation coefficient of 0.63 , which showed that moc increases as the age and height increases , and this relation was found to be statistically significant ( p < 0.0001 ) .\nas the height reflects the skeletal growth , we also found that the mmo is more significantly associated with height than age .\nthe dataset was entered into the r program for the creation of age - related percentiles .\nbest results were achieved using the following settings : l = 1 , i.e. , l constant , set to l = 0.65 by the program , m = 5 , s = 2 for girls , and l = 1 , set to 0.5 by the program , m = 7 , s = 2 for boys . table 3 depicts four linear regression models evaluating impact of age ( model 1 ) , height ( model 2 ) , age and height ( model 3 ) , and age , height , and gender ( model 4 ) on moc . in isolation ,\nage and height significantly impact mouth opening . however , impact of height on mouth opening is more significant than that of age .\nfurther , when age and height were considered together , it was only height that had influenced moc and not age .\nnorms could be designated for age with gender and height with gender [ tables 47 ] .\nage - related percentiles for moc in boys and girls are given in figure 4a and b. height - related percentiles for moc in boys and girls are given in figure 5a and 5b .\nlinear regression models for mouth opening capacity age - related percentiles of mouth opening capacity for males ( in mm ) age - related percentiles of mouth opening capacity for females ( in mm ) height - related percentiles of mouth opening capacity for males ( in mm ) height - related percentiles of mouth opening capacity for females ( in mm ) ( a and b ) age - related percentiles for mouth opening capacity in boys and girls ( a and b ) height - related percentiles for mouth opening capacity in boys and girls\nthe dataset was entered into the r program for the creation of age - related percentiles .\nbest results were achieved using the following settings : l = 1 , i.e. , l constant , set to l = 0.65 by the program , m = 5 , s = 2 for girls , and l = 1 , set to 0.5 by the program , m = 7 , s = 2 for boys .\ntable 3 depicts four linear regression models evaluating impact of age ( model 1 ) , height ( model 2 ) , age and height ( model 3 ) , and age , height , and gender ( model 4 ) on moc . in isolation ,\nage and height significantly impact mouth opening . however , impact of height on mouth opening is more significant than that of age .\nfurther , when age and height were considered together , it was only height that had influenced moc and not age .\nnorms could be designated for age with gender and height with gender [ tables 47 ] .\nage - related percentiles for moc in boys and girls are given in figure 4a and b. height - related percentiles for moc in boys and girls are given in figure 5a and 5b .\nlinear regression models for mouth opening capacity age - related percentiles of mouth opening capacity for males ( in mm ) age - related percentiles of mouth opening capacity for females ( in mm ) height - related percentiles of mouth opening capacity for males ( in mm ) height - related percentiles of mouth opening capacity for females ( in mm ) ( a and b ) age - related percentiles for mouth opening capacity in boys and girls ( a and b ) height - related percentiles for mouth opening capacity in boys and girls\npatients with temporomandibular joint diseases , craniofacial syndromes , maxillofacial trauma , oral malignancies and those who have been treated for these conditions often have complaint of restricted mouth opening . as with any other disease or condition ,\nthe aim of treatment of disorders affecting mouth opening is to restore the mouth opening to its normal value , hence the relevance of establishing normal values .\na large number of methods have been described in the literature to measure the mouth opening .\nthe measurement most often used to assess mouth opening is the interincisal distance attained during active opening by the subject .\nthis method underestimates the movement of the mandible as it does not include the overbite .\nhowever , as pointed by mezitis et al . , the functional opening of the mouth is more important .\nsufficient mouth opening to allow normal social function is clinically important for the patients and adequate access to the oral cavity for clinicians , which in effect is the interincisal distance without consideration for the overbite .\nhence , the interincisal distance has been used as a measurement of mmo in this study .\nan advantage of the incisal edge distance is that the measuring point is relatively more consistent , permanent , and more easily determined .\nwood and branco examined three methods of measuring interincisal distance and concluded that direct measurement using a ruler was the most accurate .\ndescribed how the mmo decreases in order of forward , natural , and retracted head positions . in the present study ,\nthe mmo was measured when the subjects rested their heads against a firm wall surface in an upright position to eliminate the possible influence of different head positions .\nmouth opening is influenced by a number of factors in children as they are in the period of skeletal growth .\nthe age , weight , height , gender , and race affect the mouth opening .\nrothenberg noted a significant relationship between the maximum vertical opening of the mouth and age , among 189 caucasian children , aged 414 years .\nthe present study also reported a gradual increase in mmo in different age groups of children .\na few studies have observed a gender difference in mmo among children . in the present study , a statistically significant difference was observed in between boys and girls in various age groups .\nthe study also revealed a definitive correlation between mmo and height as well as age .\nrothenberg also observed a positive correlation between mmo values in relation to weight and height in children aged 414 years of age group .\nthe observed gradual increase in mmo with increasing age , height , and body weight , as found in the present study , is due to changes in the temporomandibular joint apparatus , facial morphology , muscle development , and growth of cranial base and mandible , particularly in length . although age has the significant influence on the mmo values , a definite and stronger correlation exists between mmo and height .\nchildren with poor nutrition often have stunted growth , and their skeletal growth is hampered .\nin such cases , measurement of mmo will not correspond to the established norm for the age since the height is unaccounted for , in these malnourished children from lower socioeconomic group .\nin such cases , to measure height by age can give a false - positive value of reduced mouth opening .\nthis study is therefore providing the normal percentile for different height groups for the first time .\nthese data are important because a high number of complex surgical procedures are routinely performed in this part of the world without a proper reference value for established norms .\nassessment of mouth opening is an important part of clinical examination for the physician , surgeon , or clinician involved in the treatment of head and neck disorders and dental disorders . to diagnose an abnormality , knowledge of normal values is very important .\nreference to international data is obviously not justified as the mouth opening is clearly varied among different ethnicities . to the best of our knowledge\n, this data sample of 985 unselected children covers the entire age range of indian children where unassisted mouth opening can be measured .\nwe believe that these percentiles will therefore be of great importance for future studies as well as clinical assessment of indian children with affections of the masticatory system .", "answer": "background and aim : maximal mouth opening ( mmo ) is used as a marker of masticatory pathology . \n however , mmo among children varies considerably with their age , height , sex , and race . while accurate percentile of normal mouth opening and relationship with anthropometric measurement are not precisely defined for the indian population , we designed prospective , observational study to define the percentiles for normal mmo in our children.methods:a total of 985 children , 560 males and 425 females , in the age range of 518 years attending the pediatric clinic in a tertiary care center in western india were studied . \n in addition to the basic demographic data , mmo was measured in these children . \n the children were asked to open their mouth maximally until no further opening was possible . \n the distance from the incisal edge of the upper incisor teeth to the incisal edge of the lower incisor teeth was measured using a calibrated fiber ruler . \n statistical analysis was performed to assess the impact of other anthropometric measures such as age , gender , and height on mmo.observations:the mean mmo for males was 44.24 ( 5.84 ) mm and for females was 43.5 ( 5.19 ) mm . \n age- and height - related percentiles were created for girls and boys separately , showing the 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles from 5 through 18 years of age with 86185 cm height.conclusion:the mmo percentile range for different age and height groups is established for the normal children . \n the mouth opening seems to increase with the age and especially with the height as per the skeletal growth . \n height affects mouth opening more than the age .", "id": 516} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nemergency peripartum hysterectomy ( eph ) is a major surgical venture invariably performed in the setting of life threatening hemorrhage during or immediately after abdominal and vaginal deliveries [ 15 ] . despite advances in medical and surgical fields\n, post partum hemorrhage continues to be the leading cause of maternal morbidity and mortality .\neph is the most dramatic operation in modern obstetrics and is generally performed when all conservative measures have failed to achieve haemostasis in the setting of life threatening hemorrhage . the unplanned nature of the surgery and the need for performing it expeditiously , compound matters .\nmoreover the acute loss of blood renders the patient in a less than ideal condition to undergo emergency surgical intervention .\nthe predominant indications for eph are placenta previa / accreta and uterine atony and eph in some of them is unavoidable . however recognizing and assessing patients at risk and\nappropriate and timely intervention would go a long way in ensuring a better outcome in this otherwise difficult situation .\nhysterectomy following cesarean section ( cs ) was first described by porro , and was used to prevent maternal mortality due to post partum hemorrhage .\nthe reported incidence of eph varies from 0.24 to 8.9 per 1000 deliveries [ 16 ] , ranging from 0.33(netherland ) , 0.2 ( norway ) , 0.3 ( ireland ) , 0.5 ( israel ) , 0.63 ( saudi arabia ) and 1.2 to 2.7 per 1000 deliveries in usa [ 25810 ] . a difference in the incidence of eph is noted following vaginal delivery and cesarean section .\nwhile the incidence of eph after vaginal delivery varies from 0.1 to 0.3/1000 deliveries and is rather constant between european and us studies , the incidence of eph following cs varies widely between 0.17 and 8.7/1000 deliveries .\nthis is attributed to the proportion of women with previous cs with the concomitant risk of placenta previa andaccreta [ 16 ] .\nthe risk factors for post partum hemorrhage include coagulopathies , uterine atony , retained products of conception , precipitate or prolonged labor , fetal macrosomia or multiparity , maternal obesity and previous primary post partum hemorrhage [ 16814 ] .\naccording to one report the indication for eph which was uterine atony in 43.45% and placenta previa or accreta in 33.9% cases in 1984 changed 9 years later to placenta accreta ( 45% ) and uterine atony in 20% of the cases .\nsimilar findings are reported by others with abnormal placentation as the predominant indication , the incidence ranging from ( 45 to 73.3% ) ; and uterine atony in ( 26.6% to 35.6% ) [ 18815 ] . in recent years\n, abnormal placentation has become a more common indication due to the greater number of pregnant women with previous cesarean section deliveries [ 16 ] .\nthe incidence of previous cesarean section ranges between 59.8% in patients with adherent placenta and 75% in patients with placenta previa . in view of several such reports ,\nassociation between abnormal placentation and cesarean delivery has been suggested and the high incidence of eph is directly related to the increasing number of cesarean sections [ 1616 ] .\nthis was further substantiated by another report where the incidence of placenta previa which was 1.9/1000 after one previous cs , increased by 47 fold to 91/1000 in patients with four previous cs .\npatients with placenta previa and scarred uterus had 16% risk of undergoing eph compared to 3.6% in patients with unscarred uterus .\nadvancing age and parity are also reported to be important risk factors in developing placenta previa and accrete .\nthe incidence of eph was higher in patients with placenta previa and accreta than in patients with placenta previa alone .\nthe combination of factors including high parity , number of previous cesarean sections , abortion , previous curettage , strongly increased the likelihood of placenta previa and increased risk of abnormal adherent placenta .\ntherefore , it appears prudent for the obstetrician to prepare for the possibility of eph for massive hemorrhage in patients undergoing cesarean section with these risk factors . of concern\nhowever , is the limited experience of performing emergency hysterectomy among the younger obstetricians as according to one report from netherlands , the average chance of performing one eph is once in 11 years .\nthe decreasing rate of abdominal hysterectomy for gynecological conditions in recent years does not help matters with regard to gaining this valuable experience .\nthis implies that more effort should be undertaken to recognize the potential risk of patients requiring eph and the need for involvement of an experienced obstetrician in the management at an early stage .\neph being performed by an experienced surgeon is reported to significantly reduce the operating time , number of units of blood transfusion and hospital stay .\nthe predisposing risk factors can be determined to a certain extent by performing antenatal ultrasound with color doppler and magnetic resonance imaging ( mri ) [ 1820 ] .\nhowever , the limiting factor is the high cost of mri and extensive experience needed .\nthe measures include uterotonic drugs , uterine or hypogastric artery embolisation , hemostatic sutures , uterine or internal iliac artery ligation .\nconservative management is of particular importance in patients who are young , have low parity and who are haemodynamically stable .\nhowever while there are reports of 96% success rate following uterine artery ligation there are others who have achieved success in only 39.4% of these cases .\nthe choice between conservative management and eph should be individualized . in situations where conservative treatment is likely to fail or has failed , there should be no further delay in performing eph as delay leads to increase in blood loss , transfusion requirement , operative time , dic , and increased possibility of admission to icu [ 16 ] .\nuterine atony is an indication for eph in 20.6% to 43% of the cases [ 16817 ] .\nwhile this was traditionally the leading cause for eph the incidence has reduced due to the use of newly developed pharmacologic treatment strategies including prostaglandins .\nmultiparity and oxytocin use for uterine stimulation were found to be the risk factors for uterine atony requiring eph [ 16 ] .\ncombs et al in their large case control study of patients with post partum hemorrhage reported that pre - eclampsia , nulliparity , twins , induction , prolonged labor and augmentation were all identified as independent risk factors for uterine atony .\npatients with uterine rupture as an indication for eph ranged from 11.4% to 45.5% . the risk factor for\nthis would be multiple previous cesarean sections with a scarred uterus ( figure 1 ) .\ntotal hysterectomy is the recommended surgical method of eph due to the potential risk of malignancy developing in the cervical stump and the need for regular cytology and other associated problems such as bleeding or discharge associated with the residual cervical stump .\ncurrently the proportion of subtotal hysterectomy performed for eph ranges from 53% to 80% .\nthe proponents of subtotal hysterectomy report a lesser blood loss , a reduced need for blood transfusion , reduced operating time and reduced intra and postoperative complications .\ntotal hysterectomy should however be considered when active bleeding occurs from lower uterine segment as the cervical branch of uterine artery may remain intact .\nthe final decision to perform subtotal or total hysterectomy would be influenced by patient 's condition .\nhence , while total abdominal hysterectomy is a more convenient procedure , subtotal eph may be a better choice in certain conditions where surgery needs to be completed in a shorter time .\nuterine atony is an indication for eph in 20.6% to 43% of the cases [ 16817 ] .\nwhile this was traditionally the leading cause for eph the incidence has reduced due to the use of newly developed pharmacologic treatment strategies including prostaglandins .\nmultiparity and oxytocin use for uterine stimulation were found to be the risk factors for uterine atony requiring eph [ 16 ] .\ncombs et al in their large case control study of patients with post partum hemorrhage reported that pre - eclampsia , nulliparity , twins , induction , prolonged labor and augmentation were all identified as independent risk factors for uterine atony .\nthe risk factor for this would be multiple previous cesarean sections with a scarred uterus ( figure 1 ) . uterine rupture with life threatening hemorrhage managed by peripartum hysterectomy .\ntotal hysterectomy is the recommended surgical method of eph due to the potential risk of malignancy developing in the cervical stump and the need for regular cytology and other associated problems such as bleeding or discharge associated with the residual cervical stump . currently the proportion of subtotal hysterectomy performed for eph ranges from 53% to 80% .\nthe proponents of subtotal hysterectomy report a lesser blood loss , a reduced need for blood transfusion , reduced operating time and reduced intra and postoperative complications .\ntotal hysterectomy should however be considered when active bleeding occurs from lower uterine segment as the cervical branch of uterine artery may remain intact .\nthe final decision to perform subtotal or total hysterectomy would be influenced by patient 's condition .\nhence , while total abdominal hysterectomy is a more convenient procedure , subtotal eph may be a better choice in certain conditions where surgery needs to be completed in a shorter time .\nuterine atony is an indication for eph in 20.6% to 43% of the cases [ 16817 ] .\nwhile this was traditionally the leading cause for eph the incidence has reduced due to the use of newly developed pharmacologic treatment strategies including prostaglandins .\nmultiparity and oxytocin use for uterine stimulation were found to be the risk factors for uterine atony requiring eph [ 16 ] .\ncombs et al in their large case control study of patients with post partum hemorrhage reported that pre - eclampsia , nulliparity , twins , induction , prolonged labor and augmentation were all identified as independent risk factors for uterine atony .\nthe risk factor for this would be multiple previous cesarean sections with a scarred uterus ( figure 1 ) .\ntotal hysterectomy is the recommended surgical method of eph due to the potential risk of malignancy developing in the cervical stump and the need for regular cytology and other associated problems such as bleeding or discharge associated with the residual cervical stump . currently the proportion of subtotal hysterectomy performed for eph ranges from 53% to 80% .\nthe proponents of subtotal hysterectomy report a lesser blood loss , a reduced need for blood transfusion , reduced operating time and reduced intra and postoperative complications .\ntotal hysterectomy should however be considered when active bleeding occurs from lower uterine segment as the cervical branch of uterine artery may remain intact .\nthe final decision to perform subtotal or total hysterectomy would be influenced by patient 's condition .\nhence , while total abdominal hysterectomy is a more convenient procedure , subtotal eph may be a better choice in certain conditions where surgery needs to be completed in a shorter time .\nthe complications included blood transfusion ( 88% ) , febrile episodes ( 26.5% ) , perinatal death ( 22.8% ) , bladder injuries ( 8.8% ) , wound infection , dic , ileus , vaginal cuff bleeding and adnexectomy .\nthe maternal mortality ranged from 0 to 12.5% with a mean of 4.8% [ 168192124 ] .\nalthough no risk assessment system can predict all instances where cesarean delivery will be needed , a significant percentage of the patients who are at high risk for severe hemorrhage and the subsequent need of emergency hysterectomy can be identified before surgery .\nthe presence of preoperative risk factors should facilitate consultation , referral or transfer of patients before surgery to a tertiary care facility . due to the complexity of the surgery and decision making ,\nproper surgical measures such as hemostatic sutures or uterine or hypogastric artery ligation or embolization are options in attempting uterine conservation particularly in patients who are young and in whom future fertility is important and who are relatively haemodynamically stable .\nwhen conservative treatment is not feasible or has failed , prompt eph is performed failing which the delay would contribute to the maternal morbidity and in unfortunate cases mortality .", "answer": "background : peripartum hysterectomy is a major operation and is invariably performed in the presence of life threatening hemorrhage during or immediately after abdominal or vaginal deliveries.material and methods : a medline search was conducted to review the recent relevant articles in english literature on emergency peripartum hysterectomy . \n the incidence , indications , risk factors and outcome of emergency peripartum hysterectomy were reviewed.results:the incidence of emergency peripartum hysterectomy ranged from 0.24 to 8.7 per 1000 deliveries . \n emergency peripartum hysterectomy was found to be more common following cesarean section than vaginal deliveries . \n the predominant indication for emergency peripartum hysterectomy was abnormal placentation ( placenta previa / accreta ) which was noted in 45 to 73.3% , uterine atony in 20.6 to 43% and uterine rupture in 11.4 to 45.5 % . \n the risk factors included previous cesarean section , scarred uterus , multiparity , older age group . \n the maternal morbidity ranged from 26.5 to 31.5% and the mortality from 0 to 12.5% with a mean of 4.8% . \n the decision of performing total or subtotal hysterectomy was influenced by the patient 's condition.conclusion:emergency peripartum hysterectomy is a most demanding obstetric surgery performed in very trying circumstances of life threatening hemorrhage . \n the indication for emergency peripartum hysterectomy in recent years has changed from traditional uterine atony to abnormal placentation . \n antenatal anticipation of the risk factors , involvement of an experienced obstetrician at an early stage of management and a prompt hysterectomy after adequate resuscitation would go a long way in reducing morbidity and mortality .", "id": 517} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe overall annual incidence of intussusception in adults in the general population has been reported to be as low as 2 cases/1 000 000 persons ; adults account for ~5% of confirmed intussusceptions . as high as 90% of cases of adult intussusception\nare due to a pathological process , with neoplasms accounting for ~60% of identifiable leadpoints .\none 6-year prospective study encompassing screening of 380 999 computed tomography ( ct ) scan reports that were read as intussusception , 0.04% of cases were in adults . in adults ,\nsurgery is typically performed owing to the likelihood that a neoplastic or otherwise chronic pathology is the cause of the intussusception .\nindications to take any case to the operating room include large caliber of telescoped bowel , long length of telescoped portion , identifiable lead point and evidence of obstruction [ 24 ] .\nthe former indications owe to the increased likelihood of malignancy requiring surgical exploration and incision , and bowel wall and mesenteric ischemia in the setting of large intussusceptions .\na 61-year - old gentleman presented with a 3-day history of right - greater - than - left lower quadrant abdominal pain , distention , anorexia and one episode of emesis\n. the patient also reported only consuming liquids for 57 days prior to presentation as solid foods caused significant discomfort .\nthree weeks prior , colonoscopic evaluation of his cramping was aborted at 20 cm due to an impassable sigmoid stricture . several hyperplastic polyps and one tubular adenoma\nhis abdomen was distended and tympanic , with tenderness and fullness appreciated in the right lower quadrant .\n1 ) demonstrated small bowel obstruction due to an ileocolic intussusception , from the ileocecal valve to the splenic flexure , and collapsed distal colon .\nfigure 1:top left : origin ( arrow ) of invagination in the right lower quadrant .\nthe telescoped bowel contained terminal ileum , cecum , appendix and the entire ascending colon ( fig .\na 4.5 cm 5 cm mass was identified at the lead point , the ileocecal valve .\nresection included the right hemi - colon , cecum , appendix and 15 cm of terminal ileum .\na diverting ileostomy was created as well as a mucus fistula for post - operative antegrade colonoscopic evaluation of the remaining colon . \n\nfigure 2:left : stills from intraoperative video recording demonstrating the reduction of the intussusception in order to explore the lead point .\nright : ischemic terminal ileum ( arrow ) and palpation of the lead point at the ileocecal valve . left : stills from intraoperative video recording demonstrating the reduction of the intussusception in order to explore the lead point .\nright : ischemic terminal ileum ( arrow ) and palpation of the lead point at the ileocecal valve .\nadditional tubulovillous adenomas , tubular adenomas and hyperplastic polyps were identified throughout the excised portion of bowel .\nfigure 3:low - power ( left ) and high - power ( right ) views of lead point tumor demonstrates > 50% of the tumor composed of pools of mucin ( solid arrow ) , invasive tumor cells ( dotted arrow ) with hyperchromatic chromatin , crowded nuclei , surrounded by pools of mucin [ 57 ] .\nlow - power ( left ) and high - power ( right ) views of lead point tumor demonstrates > 50% of the tumor composed of pools of mucin ( solid arrow ) , invasive tumor cells ( dotted arrow ) with hyperchromatic chromatin , crowded nuclei , surrounded by pools of mucin [ 57 ] .\nthis patient 's presentation is exceptionally unique for both the size and cause of intussusception . to our knowledge ,\nthe few cases we found were always in the setting of malignancy , the patients presented with a similar chronologic progression with escalation of symptoms including liquid - only diets shortly before presentation .\nadditionally , the very large intussusceptions were always found in the setting of malignancy [ 1012 ] .\nit seems that a favorable ( mobile ) anatomy with an indolent process is a common thread amongst these rare cases . further compounding the uniqueness of this case is the lead point tumor 's location and histology , along with the presence of additional terminal ileum and colonic polyps .\nthe annual incidence in the united states of small bowel adenocarcinoma from 1973 - -2005 is 6.8 cases per 1,000,000 person years , as calculated by surveillance epidemiology and results ( seer ) program .\nadditionally , ileocecal adenocarcinoma of any type is sparsely described outside of a few case reports [ 8 , 9 , 1315 ] .\nmucinous adenocarcinoma tends to be a locally aggressive tumor , and metastasizes by redistribution phenomenon rather than vascular or lymphatic invasion .\npresently , we have no unifying diagnosis to correlate the multiple lesions found throughout the telescoped bowel and distal 20 cm of colon and rectum .\nhowever , it is currently estimated that up to 40% of patients with extensive polyps and a positive family history are ruled out for hnpcc by genetic testing for mismatch repair and msi , as was the case for this patient .\nnevertheless , the unique presentation of this patient allowed for expeditious removal of a classically aggressive tumor , in what appears to be the first reported case of a long - tract intussusception secondary to a mucinous adenocarcinoma of the ileocecal valve .", "answer": "abstractintussusception in adults lacks specific symptoms and is often diagnosed emergently when they present with obstruction . though intussusception certainly varies in size and location , the increased likelihood of ischemia or obstruction make large intussusceptions very rare in the literature . \n a patient admitted to our facility for small bowel obstruction was found to have extensive intussusception from the right lower quadrant to the splenic flexure , where a lead point was identified . \n histopathology revealed multiple satellite lesions surrounding the lead point tumor , which was found to be invasive mucinous adenocarcinoma of the ileocecal valve . \n while malignancy is found in 60% of lead point identifiable adult intussusceptions , a malignancy is always found in the case of an exceptionally large intussusception .", "id": 518} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe antimetabolite 5-fluorouracil ( fu ) is widely used in the treatment of solid tumors , including gastrointestinal , breast , head , and neck cancers .\ncardiotoxicity , a rare adverse effect of 5-fu , has a reported incidence of 1.2% to 18% .\nthe patient presented with typical angina and electrocardiographic changes suggestive of an ischemic coronary event during the continuous infusion of 5-fu .\nthe ischemia recurred when the infusion was stopped , and was relieved by administration of nitroglycerin followed by a sublingual calcium channel blocker .\nan 83-year - old man who had been diagnosed with stage iiic ( t4n2m0 ) adenocarcinoma of the ascending colon and who had undergone a right hemicolectomy was admitted to inje university seoul paik hospital to begin adjuvant chemotherapy , using the folfox4 regimen ( 400 mg / m 5-fu bolus infusion followed by the continuous infusion of 600 mg / m 5-fu for 22 hours on days 1 and 2 ; 200 mg / m leucovorin as a continuous infusion for 2 hours before 5-fu infusion on days 1 and 2 ; and infusion of 85 mg / m oxaliplatin on day 1 ) .\nbaseline echocardiography performed 1 month before admission showed normal left ventricular systolic function and no regional wall motion abnormality .\nhe was treated with 1,500 mg high - dose 5-fu ( 1,000 mg / m ) per day . on the morning of the 3rd day\n, he developed a severe , substernal , crushing chest pain during the continuous intravenous infusion of 5-fu ( cumulative dose 1,679 mg / m ) , which was partially relieved by administering sublingual nitroglycerin .\nthe electrocardiogram ( ecg ) showed st segment elevation with a tall t wave in leads i , avl , and v4 - 6 , and reciprocal st segment depression in leads v1 - 2 ( fig .\nthe troponin - i and ck - mb levels were 0.010 ng / ml ( reference range , 0.1 ) and 3.73 ng / ml ( reference range , 4.94 ) , respectively .\nsevere hypokinesia of the lateral wall of the left ventricle was noted on a portable bedside echocardiogram .\nthe 5-fu infusion was stopped , and the chest pain and electrocardiographic changes resolved after intravenous infusion of nitroglycerin at 30 g / min .\nemergency coronary angiography was then performed , which revealed significant stenosis in the proximal left circumf lex coronary artery ( lcx ) .\nintracoronary nitroglycerin ( 200 g ) was injected to exclude coronary vasospasm , but no change occurred ( fig .\n2 ) . intravenous ultrasound ( ivus ) showed severe luminal narrowing with a heavy concentric plaque in the proximal lcx .\npercutaneous coronary intervention of the proximal lcx lesion was performed successfully with the implantation of a drug - eluting stent ( 3.5 16 mm ; taxus , national medical center , seoul , korea ) ( fig .\nthe patient was transferred to the coronary - care unit , where 8 hours later , he reported a recurrence of the anterior chest pain .\nthe ecg also showed st segment elevation and reciprocal st changes similar to those seen in the previous ischemic events ( fig .\nthe chest pain and ecg changes persisted despite a 100 g / min nitroglycerin infusion . to rule out acute stent thrombosis ,\nthe chest pain and ecg changes were relieved after sublingual administration of 10 mg nifedipine . repeated coronary angiography showed a widely patent stent ( fig .\n4 ) . the postprocedural troponin - i and ck - mb levels were 0.010 and 4.62 ng / ml , respectively .\nechocardiography performed the next day also showed the absence of the regional wall motion abnormality and normal left ventricular systolic function .\nwe present here a case of severe cardiotoxicity mimicking acute anterolateral myocardial infarction occurring in a patient receiving 5-fu chemotherapy for adenocarcinoma of the colon .\nthe cessation of 5-fu administration and the subsequent initiation of treatment with a sublingual calcium channel blocker and nitrate resulted in a successful outcome .\nalthough the mechanism by which 5-fu exerts its cardiotoxic effects is unknown , the resolution of the patient 's chest pain and the normalization of his ecg changes with a vasodilator strongly support the vasospastic hypothesis of 5-fu cardiotoxicity .\none study postulated that 5-fu - associated cardiotoxicity is due to the uncoupling of the electromechanical mechanisms that underlie normal myocardial function , which might be mediated at the level of the cell membrane .\nrecently , kuzel et al . suggested that 5-fu promotes a hypercoagulable state ( e.g. , coronary artery thrombosis ) and observed a significant increase in fibrinopeptide a and a decrease in protein c activity during 5-fu administration . the incidence of clinically apparent 5-fu cardiotoxicity is less than 10% in patients receiving the drug .\npatients with a history of coronary artery disease ( cad ) have a significantly increased risk of 5-fu - induced cardiotoxicity .\nalthough our patient did not have a history of cad , a large atheromatous plaque was found on coronary angiography and ivus .\ntherefore , during 5-fu infusion , close , careful monitoring of patients , especially those with pre - existing cad or cad risk factors , is mandatory .\nprophylactic calcium channel blockers or nitrates should be administered to patients with cad during 5-fu administration , to prevent vasospasm .\none study proposed that impaired renal function is also a risk factor for 5-fu cardiotoxicity .\nalthough it is not clear whether the cardiotoxic metabolites undergo renal excretion , the pathophysiological effect of 5-fu on the myocardium is likely to increase with decreased renal function .\nthus it is necessary to clarify which patients may benefit from optimum anti - angina prophylaxis and careful , close monitoring .\nthe incidence of 5-fu - related cardiotoxicity appears to be dependent on the dosage and delivery system .\ninfusion of 5-fu , which is now being used more frequently and at higher doses instead of bolus therapy , may be a significant factor in the development of 5-fu cardiotoxicity . in one study ,\nnine patients treated with a higher - dose ( > 800 mg / m ) continuous infusion of 5-fu died suddenly . interestingly , despite stopping the 5-fu , the chest pain and ecg changes recurred in our case .\none series reported that 19% of the patients developed reversible angina pectoris during treatment , which lasted for up to 12 hours after cessation of the infusion .\nthe possible mechanisms of delayed angina are the late release of potent vasoactive 5-fu metabolites , which accumulate over time due to degradation of 5-fu .\ntherefore , a calcium channel blocker or nitrates should be administered after stopping the 5-fu when 5-fu - induced cardiotoxicity occurs .\nthe long - term outcome of patients with 5-fu - related cardiotoxicity has not been investigated extensively . as with our case ,\npatel et al . recently reported interval improvements in the left ventricular wall motion abnormalities in echocardiography performed 8 to 15 days following the initial study .\nwhen cardiotoxicity occurs , 5-fu treatment is usually discontinued due to its very high recurrence rate ( 90% )\n. the re - administration of 5-fu is not recommended , and a different chemotherapy regimen should be considered .\ninterestingly , meydan et al . continued 5-fu chemotherapy in one group who experienced 5-fu cardiotoxicity due to the absence of an alternative drug and found that subsequent serious , hemodynamic consequences were easily controlled with nitrate treatment . for the remaining patients ,\neither 5-fu was removed from the combination regimen or an alternative drug was started and no cardiotoxicity developed subsequently . in summary , although 5-fu - associated cardiac toxicity is rare , it may cause angina , myocardial infarction , and even sudden death .\nphysicians should be aware of this potentially lethal side effect and should start the proper treatment when 5-fu cardiotoxicity develops .\nthis case supports the vasospastic hypothesis of 5-fu cardiac toxicity , indicating that a calcium channel blocker may be effective for prevention or treatment of 5-fu cardiotoxicity .", "answer": "cardiotoxicity associated with 5-fluorouracil ( fu ) is an uncommon , but potentially lethal , condition . \n the case of an 83-year - old man with colon cancer who developed chest pain during 5-fu infusion is presented . \n the electrocardiogram ( ecg ) showed pronounced st elevation in the lateral leads , and the chest pain was resolved after infusion of nitroglycerin . a coronary angiogram ( cag ) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery . \n coronary artery spasm with fixed stenosis was considered , and a drug - eluting stent was implanted . \n after 8 hours , the patient complained of recurring chest pain , paralleled by st elevation on the ecg . \n the chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine . \n repeated cag showed patency of the previous stent . \n this case supports the vasospastic hypothesis of 5-fu cardiac toxicity , indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-fu cardiotoxicity .", "id": 519} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbiological or biopharmaceuticals are drugs produced from living cells through the biological process , and mimic natural biological substances such as hormones .\nbiosimilars are copy drugs similar to biological drugs that has already been authorized ( the biological reference medicine ) , hence similar but not identical .\nindian guidelines define a similar biologics as a biological product / drug produced by genetic engineering techniques and claimed to be similar in terms of safety , efficacy and quality to a reference biologics , which has been authorized by drug controller general of india ( dcgi ) for safe use in india .\nthe active substance of biosimilar medicine is similar to one of the biological reference medicine and used in general at the same dosage to treat the same disease .\nbiosimilars are entity based ( including product - process ) , regulatory based ( under an abbreviated testing ) , and market based ( same manufactures , different trade name ) .\nbiosimilars also known as similar biological products , follow - up biologics , subsequent entry biological , second entry biological , biogenerics , multisource products , and off - patent biotech products as synonyms .\ngeneral public and insurance companies prefer economic alternatives , the long - term economic consequence of using biosimilars have not been studied\nbiosimilars are a new class of drugs intended to offer comparable safety and efficacy to the reference , off - patent biological .\nthe active protein structure of biologicals makes them more prone to induce an acute and chronic immune response .\nthe overall risk is modest with biosimilars , but regulatory pathways are required because of structural complexity , manufacturing process and risk for immunogenicity .\nthe problems / limitations with biosimilar are that , the two biosimilar have a different origin , the two biosimilars may have same therapeutic effect , may have different side - effects and hence require thorough testing .\nthe main reason of biosimilar drug development is the expiry of patent protection for many biological medicines [ table 1 ] .\npatent expiration of biological / biopharmaceuticals * biopharmaceuticals are different from the conventional small molecule drugs because of the size and complexity of the active substance and nature of the manufacturing process .\neven minor change in the process can lead to the fatal outcome ( process is product ) , safety , and efficacy issues .\nfor epoietin ( erythropoietin ) , minor change in the packaging process caused pure red cell aplasia .\neuropean medicines agency ( emea ) and committee for the medicinal product for human use ( chmp ) raised the objection that marvel insulin and reference human insulin were not comparable .\n, withdrew its application as they were unable to meet the standards set by chmp , but biosimilar insulin continues to flood indian market .\nhence , legal and regulatory principals applicable to generic drugs can not be applied to biosimilars .\nemea - chmp has published product specific guidelines to establish the similarity in terms of safety , efficacy and quality of biosimilar product . according to these guidelines\nmoreover , in order to support pharmacovigilance monitoring , the specific product given to the patient should be clearly identified .\nthe active substance of the biosimilar product must be similar in molecular and biological terms to the active substance of the reference medicinal product , and the same reference product throughout the comparability program .\nthe pharmaceutical form , doses and route of administration of the biosimilar and the reference product should be the same .\nif the reference product has more than one indication , the safety and efficacy for all indications have to be justified or demonstrated for each indication separately .\nthe issue of immunogenicity should always be addressed , and its long - term monitoring is necessary .\nfda was given the authority to approve biosimilars , including interchangeable , to maintain safety , efficacy , and quality of biosimilar product .\n abbreviated pathway for approval of biologics that are biosimilar to already approved products .\nthe abbreviated pathway will eliminate unnecessary and unethical testing of biosimilars in animal and human .\nthe patient protection and affordable care act of 2010 ( usa ) also supports this .\nthe new india guidelines draft guidelines on similar biologics : regulatory requirements for marketing authorization in india , were announced in june 2012 , by department of biotechnology ( dbt ) .\nthe indian guidelines on similar biologics address the pre - marketing and post - marketing regulatory requirement ( i.e. , comparability exercise ) , and also address the requirements related to manufacturing process and quality control .\nas such these indian guidelines on similar biologics are comparable in many respects to biosimilar guidelines of usa and eu .\nindia has adopted a sequential approach ( like stepwise approach - us and eu ) to market biosimilar products .\nthe review committee on genetic manipulation of the genetic engineering approval committee ( geac ) with the permission of dcgi , approve clinical trials to be conducted in india related to biosimilar therapeutic products .\nthe biosimilar has to demonstrate comparable data of non - clinical studies viz . , pharmacokinetics and toxicology ( safety pharmacology , reproduction toxicology , mutagenecity and carcinogenicity ) and clinical studies ( efficacy and tolerability for each indication ) before it gets approval for all indication of the reference medicine .\nbiosimilars in india consist primarily of vaccine , monoclonal antibodies , recombinant proteins and diagnostics , insulin ( wosulin , insugen , recosulin ) , erythropoietin ( hemax , epofer , wepox , ceriton , epofit ) , hepatitis b vaccine ( shanvac b , revac b , enivac b , biovac b , genevac b , bevac ) , granulocyte colony stimulating factor ( g - csf grastim , neukine ) , streptokinase ( indikinase , shankinase , stpase ) , interferon alpha-2b ( shanferon ) , rituxinab ( mab ) , epidermal growth factor receptor ( anti - egfr ) ( mab)(reditux , biomab - egfr ) .\nstatus of similar biologics in india there are about 100 biopharmaceutical companies actively involved in research and development , manufacturing and marketing of biosimilar therapeutic products in india .\nthere were 14 therapeutic drugs ( similar biologics ) available in 50 brands in 2005 ; the number has increased to 20 therapeutic drugs in 250 brands in 2011 .\nbiosimilar therapeutic products include insulin , erthropoietin , chorionic gonadotropin , streptokinase , interferon and heparin .\nthe growing biosimilars market offers huge potential for companies involved in manufacturing , research and development .\npharmacovigilance is more important for biosimilar drugs because these are not reference medicine as such , and are from different manufacturer from the reference products .\nmany adverse effects may appear only after a biosimilar drug is used more extensively , for a longer period of time , in a greater number of patients .\nboth manufacturers and prescriber should be aware of the importance of post marketing vigilance , and careful on patients taking biosimilar .\nbiosimilar are not generic ; biologics are larger and more complicated than chemical drugs , due to the complexity of biological / biotechnology derived products the generic approach is scientifically not appropriate for biosimilar products .\nthe challenge with biosimilars is to know the differences which matter clinically . the specific product given to the patient", "answer": "biologic products are being developed over the past three decades . \n the expiry of patent protection for many biological medicines has led to the development of biosimilars in uk or follow on biologics in usa . \n this article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines . \n appraisal of published articles from peer reviewed journals for english language publications , search from pubmed , and guidelines from european medicines agency , us food drug administration ( fda ) and india were used to identify data for review . \n literature suggest that biosimilars are similar biological products , i.e. , comparable but not identical to the reference product , are not generic version of innovator product and do not ensure therapeutic equivalence . \n biosimilars present more challenges than conventional generics and marketing approval is also more complicated . to improve access , \n us congress passed the biologics price competition and innovation act 2009 and us fda allowed abbreviated pathway for their approval . \n u.s law has defined new standards and terms and ema scientific guidelines have also set detailed approval standards . \n india being one of the most preferred manufacturing destinations of biosimilars , there is a need for stringent safety and regulatory guidelines . the new india guidelines draft guidelines on similar biologics were announced in june 2012 , by department of biotechnology at boston bio and available online .", "id": 520} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvideo laryngoscopes ( vl ) which work on the principles of indirect laryngoscopy have become popular in clinical practice .\nthey provide a significantly better view of the larynx , which may be useful in difficult tracheal intubation scenarios . the key novel feature of these \nindirect laryngoscopes is that they facilitate visualisation of the vocal cords without the need to align the oropharyngeal and tracheal axes .\nkaplan and berci introduced c - mac vl ( karl storz , tuttligen , germany ) in 2003 .\nit has been found to improve cormack - lehane ( c - l ) grading by 2 to 1 grade and possibly aid easier intubation .\nit provides both a direct laryngoscopic view and a small digital camera view that is displayed on the video screen , in contrast to many previous vls .\nrecognition of the anatomical structures and anomalies is easier , and manipulation of airway devices is facilitated .\nnasotracheal intubation ( nti ) is often required for head and neck surgeries like tonsillectomies .\ndirect laryngoscopy with the macintosh blade , with the use of magill 's forceps to direct endotracheal tube ( ett ) into glottic opening , is time - consuming and may lead to trauma to surrounding structures and damage ett cuff .\nhence , this study was conducted to assess the intubating conditions , using the conventional macintosh laryngoscope and the storz c - mac vl during nti in paediatric patients posted for tonsillectomy surgeries .\nthis prospective randomised study was conducted after obtaining approval from the institutional review board ( iec no .\npatients of either sex , aged between 8 and 18 years , belonging to american society of anesthesiologists physical status i , ii and mallampati grade i , ii were included and study was conducted between january 2013 and june 2014 . parents who refused to give consent , patients with significant systemic disease and patients having contraindications for nti were excluded from the study .\nthe procedure was explained to the patients and written informed consent from parent / guardian was obtained .\npatients in group 1 underwent conventional laryngoscopy using macintosh direct laryngoscope and group 2 underwent videolaryngoscopy using c - mac vl for nasal intubation .\nthe sample size was estimated based on a pilot study carried out in 10 patients where it was found that mean intubation times for the macintosh group , and the c - mac group were 55 s and 45 s respectively with standard deviation ( sd ) of 5 s. based on these figures and using alpha error = 0.05 and 0.85 power of the study , we got the required sample size of 25 each . hence , we recruited 30 into each group by increasing the sample size by 5 .\nthe investigator who performed the intubation in this study had previously performed about 100 nti using c - mac vl .\nafter connecting the routine pre - induction monitors , baseline values of systolic blood pressure ( sbp ) , diastolic blood pressure ( dbp ) , mean blood pressure ( mbp ) , heart rate ( hr ) and oxygen saturation ( spo2 ) were recorded .\nall patients were pre - medicated with injection glycopyrrolate 10 g / kg , injection fentanyl 2 g / kg and injection midazolam 10 g / kg intravenous ( iv ) .\nanaesthesia was induced with injection propofol 2 mg / kg iv and neuromuscular blockade achieved with injection vecuronium 0.1 mg / kg .\npatients were ventilated with oxygen , nitrous oxide ( 33:67 ratio ) and end - tidal concentration of isoflurane 0.81.2 as observed on the gas monitor for initial 4 min , followed by ventilation with 100% oxygen for 1 min before intubation .\npreservative free injection lignocaine 1.5 mg / kg iv was administered 90 s before intubation .\nfive minutes after giving injection vecuronium , ensuring adequate muscle relaxation , lubricated appropriate sized nasotracheal ett was inserted through the most patent nostril until its tip lay in the oropharynx .\nlaryngoscopy was then performed using either macintosh laryngoscope ( blade size 2 or 3 ) or storz c - mac vl ( macintosh blade size 2 or 3 ) as per the group and a view of laryngeal opening was obtained .\ninitially , attempt was made to pass the ett through the vocal cords without the aid of manoeuvres ( m0 ) .\nif difficulty was encountered , additional external manipulations ( m1 ) such as head flexion , rotation of tube and backwards , upwards , rightwards pressure ( burp ) were used . in case of failure to intubate using above manoeuvres , cuff of the ett\nwas inflated with approximately 10 ml of air and the ett brought into view ( m2 ) ( as per study done by baddoo hk et al . ) .\nonce the tip of ett was in the glottic opening , cuff was deflated ; the ett was then advanced into the trachea and then cuff was reinflated .\nif this technique failed then , cuff was deflated , and magill 's forceps alone ( m4 ) or in combination with burp ( m5 ) was used to position and guide the tube .\nthe manuoevres were followed in the sequence described in table 1 . if there was failure to intubate with all the above - said manoeuvres , oral intubation was performed .\ncorrect placement of ett was confirmed by auscultation over the chest for bilateral equal air entry and using capnograph .\nsequence of additional manoeuvres used in the study during this procedure , hr , sbp , dbp , mbp and spo2 were recorded every minute for the initial 5 min after induction of anaesthesia , and thereafter at 5 min intervals for next 15 min .\nif a decrease in saturation to 90% or lower was observed during nasal intubation then oral intubation was performed .\nparameters noted during the study were : c - l grading , time required for intubation , intubation without any manoeuvre ( m0 ) , need for the manoeuvres , type of manoeuvre ( m1m5 ) used , haemodynamic changes , lowest recorded spo2 during or immediately after intubation attempt and occurrence of any other complications .\nduration of nti was defined as the time taken from the insertion of the ett through the nostril , till passage of tube through vocal cords by visual confirmation by the intubating anaesthesiologist .\nduration of nti more than 120 s , fall in spo2 below 90% during the procedure were considered as failed nti .\ndata collected were coded , tabulated , and then analysed using statistical package for the social sciences ( spss 20 , ibm , armonk , ny , united states of america ) computer package .\nmann - whitney u - test was used for analysing age , sex , c - l grading and for comparing the duration of intubation between both groups .\nindependent - t - test was used to compare haemodynamics with respect to hr , sbp , dbp , mbp in both groups . a difference with the adjusted p\ndemographic profiles were evenly distributed between both groups . in group 1 , 86.7% of patients and in group 2 , 96.6% had c - l grading of 1 and remaining patients had c - l grading of 2 , which was not statistically significant ( p = 0.35 ) .\nduration of intubation was significantly shorter in group 2 compared to group 1 patients . in group 1 , 36.6% of patients and in group 2 , 93.3% of patients were intubated within 2 min which was statistically significant p = 0.001 [ figure 1 ] . comparison of intubation time between the groups in group 1 , 3.3% of patients and in group 2 , 23.3% of patients were intubated successfully without the application of manoeuvres ( m0 ) .\napplication of optimisation manoeuvres ( m1m5 ) was needed more in group 1 compared to group 2 ( c - mac ) ( 97% vs. 77% ) and was statistically significant p = 0.001 [ figure 2 ] . in group 1 , 30% of patients and in group 2 , 53.3% patients needed additional external manipulation ( m1 ) .\nonly 6.7% patients of either the groups were intubated using cuff inflation technique alone ( m2 ) . combined use of cuff inflation with external laryngeal manipulation ( m3 ) was not useful in both groups .\nuse of magill 's forceps alone ( m4 ) and m4 with external manipulation ( m5 ) were required more in group 1 compared to group 2 ( m4 - 37% vs. 13% ) ( m5 - 23% vs. 3% ) .\n( m3 = combined use of cuff inflation with external laryngeal manipulation was not useful in both the groups ) after induction , haemodynamic parameters ( hr , sbp , dbp and mbp ) decreased in both groups when compared to pre - induction values . at the 1 min after intubation ,\nthe values increased in both groups , but there were no intergroup differences and both the parameters returned to baseline after 5 min after nti [ table 2 ] .\nno complications ( drop in spo2 , dental trauma , etc ) were observed during the procedure in both groups .\nc - mac vl allows adequate glottic view , without the need for aligning oropharyngeal and laryngeal axes .\nwe found no significant difference in airway assessment using c - l grading in both groups .\nthis can be explained by the fact that both groups of patients were of similar demography and patients with airway difficulties were excluded from the study .\nduration of nti was significantly decreased in group 2 in comparison with group 1 patients .\nc - mac vl has slim blade profile and edges are inclined , thus reducing the potential contact area of the blade with the upper incisors .\nit magnifies airway view and allows supporting staff to optimise their assistance such as applying adequate external manipulation as necessary .\nthe anterior angulation of the blade and placement of the video camera allow the operator to see structures that would be difficult or even impossible to see under direct vision .\nthe majority of patients in group 1 required different manoeuvres as per study protocol . external laryngeal manipulation ( m1 )\nthis can be explained by the fact that there was requirement of more hand - eye coordination while viewing the glottis on vl monitor and intubating the patient even with experienced anaesthesiologists .\na previous study showed that cuff inflation technique ( m2 ) helps to lift ett from the posterior pharyngeal wall , thus helping to bring it into view and also directs it towards the glottis .\nthis technique of cuff inflation has been described for blind nasal intubation in spontaneously breathing patients .\nhowever , the technique was found to be less useful for successful intubation in this study .\ncombined use of cuff inflation with external laryngeal manipulation ( m3 ) was not useful in this study .\ndirect laryngoscopy requires elevation of the laryngoscope blade , moves the larynx upwards and elevates the glottis .\nthus , lengthens the distance between the glottic orifice and the posterior pharyngeal wall and also makes the nasally introduced tube slide upwards and then downwards in sequence .\nthus , it often requires the use of magill 's forceps to align this ett tip with the glottic inlet and its use may sometimes lead to trauma to surrounding structures , damage to ett cuff .\nmagill 's forceps alone ( m4 ) and m4 with additional external manipulation ( m5 ) were needed more in group 1 as compared to group 2 .\nsimilar studies conducted by kaki et al . and hirabayashi and seo concluded that vls needed lesser use of magill 's forceps for nti .\nc - mac vl helped the supporting staff to assist intubation , using less invasive manoeuvres and thus may prevent trauma to oral cavity , damage to ett cuff .\nit was also observed that there was a positive correlation between the number of manoeuvres used and the intubation time required in both groups .\npatients in group 1 required longer time ( 2 min ) to intubate than group 2 ( 1.5 min ) when the use of additional manoeuvres of the highest level ( m5 ) was required . for good glottic view\n, videolaryngoscopy requires the application of lesser force as compared to direct laryngoscopy to the base of the tongue .\ntherefore , videolaryngoscopy is less likely to stimulate pressor - response and induce local tissue injury .\nin contrast , both groups in our study had similar intubation responses which returned to baseline after 5 min .\nthe difference between both groups preoperatively , before induction and after intubation was statistically insignificant .\nfurther studies are required to know its utility in paediatric patients with difficult airways as well as in adult patients posted for nasal tracheal intubation .\nlimitation of this study was that anaesthesiologist could not be blinded to the type of device being used for nti .\nthe study was limited to only sixty patients considering intubation time as the primary outcome parameter .\nlarger number of enrolled cases are required to assess other parameters of the nasotracheal intubating conditions .\nstorz c - mac vl provided better glottis visualisation as compared to conventional macintosh direct laryngoscope .\nlesser time was required for intubation and there was lesser need for magill 's forceps during nti .\nhowever , requirement of additional external manipulations ( m1 ) was more with the c - mac vl group .\nthus , c - mac vl improves the nasotracheal intubating conditions and can be superior alternative to macintosh laryngoscope in clinical practice in paediatric patients .", "answer": "background and aims : c - mac video laryngoscope ( vl ) with macintosh blade has been found to improve cormack - lehane ( c - l ) laryngoscopic view as well as intubating conditions for orotracheal intubation . \n however , studies done on the performance of c - mac vl for nasotracheal intubation ( nti ) are very few in number . hence , we compared laryngoscopy and intubating conditions between macintosh direct laryngoscope and c - mac vl for nti.methods:sixty american society of anesthesiologists physical status i , ii patients , aged 818 years , posted for tonsillectomy surgeries under general anaesthesia with nti were randomised , into two groups . \n patients in group 1 were intubated using macintosh direct laryngoscope and group 2 with c - mac vl . \n c - l grading , time required for intubation , need for additional manoeuvres and haemodynamic changes during and after intubation were compared between the groups.results:c-l grade 1 views were obtained in 26 and 29 patients in group 1 and group 2 , respectively ( 86.7% vs. 96.7% ) . \n remaining patients were having c - l grade 2 ( 13.3% vs. 3.3% ) . \n duration of intubation was less than a minute in group 2 ( 93.3% ) . \n need for additional manoeuvres ( m1m5 ) were more in group 1 ( 97% vs. 77% ) . \n m1 ( external manipulation ) was needed more in group 2 compared to group 1 ( 53.3% vs. 30% ) . \n magill 's forceps alone ( m4 ) and m4 with additional external manipulation ( m5 ) were needed more in group 1 compared to group 2 ( 60% vs. 16%).conclusion : the overall performance of c - mac vl was better when compared to conventional direct macintosh laryngoscope during nti in terms of glottis visualisation , intubation time and need for additional manoeuvres .", "id": 521} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnephrotic syndrome in the first year of life in two thirds of cases is caused by mutations in four genes ( nphs1 , nphs2 , wt1 , and lamb2 ) .\nthe wilms tumor suppressor gene 1 ( wt1 ) encodes a transcription factor involved in kidney and gonadal development .\ndrash syndrome ( dds ) and frasier syndrome ( fs ) , two syndromes characterized by nephrotic syndrome ( ns ) with either diffuse mesangial sclerosis ( dms ) in dds or focal segmental glomerulosclerosis ( fsgs ) in fs , genitourinary defects and a higher risk of developing wilms tumor in dds , or gonadal dysgerminoma in both dds and fs .\n. recently published three children with fsgs on renal biopsy and wt1 mutations , who responded to intensified therapy consisting of oral cyclosporine a ( csa ) in combination with oral or intravenous glucocorticoids .\nthe mechanism of csa action in minimal change disease was the inhibition of nuclear factor of activated t cell ( nfat ) signaling in t lymphocytes .\nhowever , the therapeutic effect of csa in genetic nephrotic syndrome is probably related to a direct influence of csa on podocytes . in this report\n, we present a patient with denys drash syndrome , in whom the calcineurin inhibitors were found to induce total remission .\nour patient is the first child of non - consanguineous young parents ( mother 32 , father 34 years ) without any past medical history of kidney diseases .\nthe infant was born at 41 weeks gestation ( birth weight 3,450 g , length 55 cm ) .\nthe delivery and neonatal period were normal . at the age of 7 months , she was hospitalized for the first time in the pediatric nephrology department because of proteinuria and hematuria , which was found in routine urinalysis performed before the vaccination . on admission ,\nphysical examination revealed no edema , normal female external genitalia , and normal body weight and height for chronological age .\ninitial laboratory investigations revealed variable non - selective proteinuria 200960 mg / dl in morning sample , protein / creatinine ratio 27 g / g , hypoproteinemia ( 4.79 g / dl ) , hypoalbuminemia ( 3.0 g / dl ) , hypercholesterolemia ( 299 mg / dl ) , thrombocytosis ( 567 10/l ) , and reduced levels of igg and iga .\nthe serum creatinine level was 0.23 mg / dl , urea was 8 mg / dl , and the glomerular filtration rate was 133 ml / min/1.73 m by the schwartz formula .\nantinuclear antibodies were negative , and the level of c3 and c4 were within normal limits .\nchromosomal analysis demonstrated karyotype 46 , xx , and the biopsy of the kidney demonstrated diffuse mesangial proliferation and diffuse fibrillar increase , what may represent early stage of diffuse mesangial sclerosis .\nthe glomerular lesions contained high amount of fibrils in the mesangial matrix with diffuse mesangial proliferation .\nimmunofluorescence on frozen sections using rabbit polyclonal antisera against human igg , iga , igm , and c3 revealed only weak segmental igm staining .\nthe molecular genetic analysis was performed in the laboratory at the university of michigan in the usa .\nmutation analysis of exons 8 to 9 of wt1 was performed , and the mutation r394w ( c. 1180 c > t ) was found in our patient .\nthe treatment with enalapril ( 1.25 mg / day ) , which was started after the admission and was continued for 11 months , did not change the proteinuria significantly .\nthere was no reduction in proteinuria after 4-week oral prednisone treatment ( 60 mg / m / day ) .\nseven months later , we started the therapy with csa ( 6 mg / kg/24 h in two divided doses ) .\nthe pre - dose / trough ( c0 ) csa level was 104.4 ng / ml .\nthe serum total protein was ( 6.47 mg / dl ) , albumin ( 4.26 mg / dl ) , cholesterol 197 mg / dl , and platelet count 385 10/ql .\ncreatinine level was 0.32 mg / dl and the glomerular filtration rate was 147 ml / min/1.73 m. the pre - dose / trough ( c0 ) csa level was 95.03 ng / ml .\nat the 6 month of the treatment , we decided for csa dose reduction to 4.5 mg / kg , but a month later , slight proteinuria was observed .\nnow csa treatment is continued with the higher dose ( 6 mg / kg/24 h ) .\nthe ultrasonography examination , performed every 3 months , has not revealed any signs of tumor .\nwe report the benefits of csa treatment of the patient with glomerulopathy associated with wt1 mutation as seen in denys drash syndrome .\nthe girl in this report had early - onset srns secondary to dms , what was confirmed in kidney biopsy .\ngenetic studies showed mutations in intron 9 of wt1 gene c. 1180 c > t. this is the most common mutation found in dds .\nmutations in exons 8 and 9 of the wt1 gene have been found in patients with isolated srns and in srns associated with wilms tumor or urogenital malformations .\n. indicated that screening of wt1 exons 8 and 9 in patients with sporadic srns is sufficient to detect pathogenic wt1 mutations .\nit is possible that our patients have an incomplete form of dds ; however , it corresponds to the observation of ismaili et al . , who reported the presence of wilms tumor in only one of two patients with dds .\nchernin et al . in the recent publication suggested that missense mutations can occur with and without wilms tumor . in our patient ,\nin this situation , csa therapy was started with a significant reduction of proteinuria and remission of nephrotic syndrome .\nthree months later , complete remission of proteinuria was found . whereas genetic forms of nephrotic syndrome do not respond to therapy with immunosuppressive drugs ,\npartial remission has been reported following therapy with calcineurin inhibitors in patients with nphs2 , frasier syndrome , mutations of the phospholipase c epsilon gene ( plce1 ) , and alport syndrome [ 3 , 4 ] .\nreported three children with fsgs associated with wt1 mutation treated with combined csa and prednisone therapy given for 6 and 12 months .\nin long - term observation , the authors observed remission of ns and significant reduction of proteinuria .\nthe therapy does not seem to be accompanied by a significant loss of renal function on the short term .\nwe plan to continue the treatment with the lowest possible dose which controls the proteinuria .\nit was considered that the main effect of csa treatment in nephrotic syndrome caused by t cell dysfunction was the inhibition of nfat signaling in t cells .\nhowever , it was found that csa can also reduce proteinuria in non - immunological diseases , raising doubts about the above hypothesis . in genetic diseases , mechanisms\nsimilarly , the afferent arteriole vasoconstriction , which is induced by csa , does not seem to play the main role in the reduction of proteinuria .\nthis fact was suggested by zietse et al . , who studied the influence of csa on proteinuria in different glomerulopathies and found the reduction of protein excretion in minimal change disease , but not in membranoproliferative glomerulonephritis or fsgs .\nthe possible mechanism in genetic ns may be that proposed by faul et al . .\nthe authors suggested the influence of csa on synaptopodin , an actin binding protein that was highly expressed in podocytes .\nit was shown that calcineurin caused the dephosphorylation of synaptopodin and caused proteinuria via its degradation .\nthis mechanism seems to be possible because significant reduction ( 30% ) of csa dose caused the slight proteinuria in our patient , so we increased the dose to initial one .\nour observation seems to confirm the theory of mundel and reiser , who suggested that proteinuria is due to an enzymatic disease of the podocytes .\nit is likely that podocytes are a direct target of csa , which preserves the phosphorylation - dependent synaptopodin-14 - 3 - 3beta interaction , protects synaptopodin from degradation , and preserves a stable filtration barrier [ 7 , 17 ] .\nthe fact that the antiproteinuric effect of csa results from a direct effect on podocytes explains not only its beneficial role in most steroid - resistant and steroid - dependent nephrotic syndromes but also the fact of cyclosporine dependency .\nour observation and observations of other authors [ 3 , 4 , 9 , 12 , 15 ] confirm the beneficial effect of csa treatment in genetic ns ; however , the potential nephrotoxicity of this drug will probably not allow the long - term use .", "answer": "denys drash syndrome ( dds ) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis ( dms ) , genitourinary defects , and a higher risk of developing wilms tumor . \n it is commonly assumed that the dms is unresponsive to any medications . in this report , we present a patient with denys drash syndrome , in whom the cyclosporine a ( csa ) was found to induce total remission . \n this observation and observations of other authors confirm that in genetic forms of nephrotic syndrome , the proteinuric effect of csa may be due to a non - immunologic mechanism . \n we confirm the beneficial effect of csa treatment in dds ; however , the potential nephrotoxicity of this drug will probably not allow long - term use .", "id": 522} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhirsutism is an abnormal growth of terminal hairs in areas dependent on androgen in women and is referred as an increase of unwanted hairs more than what is acceptable in a race or society .\nhirsutism is a cultural attitude and what is considered hirsutism in one culture may be considered typical in another .\nfor example , a woman who is regarded hirsute in a culture may be completely normal in another culture . in the conducted studies ,\nthe difference in iran from the foreign studies is probably due to racial difference and difference of age groups of the studies .\nhirsutism is a symptom of hyperandrogenism and different causes such as polycystic ovary syndrome ( pcos ) , congenital adrenal hyperplasia , androgen - secreting ovarian and adrenal tumors , cushing syndrome , pregnancy , hyperprolactinemia , gonads disorders , drug intake , and idiopathic causes can induce it .\nits prevalent symptoms include obesity , acne , menstrual disorders , and alopecia which can cause affliction of the person with pcos .\nabout half of the hirsute people are obese , and there is a significant relationship between obesity and hirsutism in different studies .\nhyperprolactinemia is observed in about 510% of the patients with amenorrhoea which is almost accompanied by galactorrhoea and one of its important complications is infertility .\nconsidering frequency of hirsutism and failure to study prolactin ( prl ) level in patients , the performance of this study about hirsutism causes can help confront with the hirsute patients to find the main cause and determine a suitable solution for patients .\nin this cross - sectional study , all patients with hirsutism referring to the dermatology clinic of babol city , northern iran , were included in the study . after giving necessary explanations about this study and receiving a letter of consent , a questionnaire including a history of the disease and physical examination\nhistory of disease included age , marital status , term of affliction with hirsutism , menstrual disorder ( < 21 days and more than 35 days ) , history of galactorrhoea , history of androgenic alopecia , history of hirsutism , history of thyroid disease , pcos , and treatment for infertility ( bromocriptine , clomiphene , and metformin ) .\nmorning venous blood samples were obtained after a 12 h overnight fasting from the subjects at days 2 to 3 of a menstrual cycle , and immediately centrifuged , and the serum was frozen and stored until all the samples from all the cases had been collected .\nfollicle stimulating hormone ( fsh ) , luteinizing hormone ( lh ) , prl , dehydroepiandrosterone sulfate ( dhea - s ) , 17-oh progesterone , testosterone , sex hormone - binding globulin ( shbg ) , thyroid - stimulating hormone ( tsh ) , t3 , and t4 tests were performed for all patients . in case ,\nthere was suspicion about pcos syndrome , pelvic ultrasonography was requested for the patients . according to the definition , the cases with more than ten cysts with dimensions of 28 mm in ovary were called pcos . in the case of confirming the diagnosis ,\na chemiluminescence immunoassay system was used for the determination of sex hormones ( diasorin , germany ) .\ntestosterone of more than 1.2 ng / ml , dhea - s of more than 340 g / ml , prl of more than 27 ng / ml , lh of more than 27\niu / l , and fsh of more than 15 iu / l , 17-hydroxy progesterone of more than 300 ng / ml , shbg of more than 20 nmol / l , tsh of more than 5.1 miu / ml , t3 of more than 3.1\ndata were collected and coded . after being recorded in the designed tables , it was entered in version 21 of spss version 21 for windows ( ibm corp , armonk , ny , usa ) and then statistically analyzed .\nthe obtained information was described by presenting tables of frequency and the related figures . to describe\nqualitative characteristics , frequency and percent were used and for quantitative characteristics , mean and range of variations were used . to compare qualitative variables , chi - square test was used and to determine the relationship between quantitative variables , a t - test was used in case of normal distribution .\nduring the study period , 200 patients were included . the mean age of the studied people was 26.17 6.05 years .\nthe minimum age of patients was 16 years , and the maximum age was 45 years .\neighty - five patients ( 42.5% ) were single , 115 ( 57.5% ) were married , and 23 married patients ( 20% ) underwent pharmacotherapy due to infertility .\nhalf of the patients ( 100 patients ) had regular menses , whereas the remaining 100 patients had irregular menses .\nsixty percent found to have a first - degree family history of hirsutism . in studied patients , 18 patients ( 9% ) had galactorrhoea , 45 patients ( 22.5% ) had androgenic alopecia , and 29 patients ( 14.5% ) had the history of ovary cyst .\nout of the 200 patients in the study , 25 patients ( 12.5% ) had hyperprolactinemia .\nthe mean level of prl in the studied people was 16.69 7.24 ng / ml . table 1 shows the comparison of the patients complaint with hyperprolactinemia . comparing the studied variables with hyperprolactinemia in the studied patients the mean age of the people with hyperprolactinemia was 26.16 5.51 years , and the mean age of the people without hyperprolactinemia was 26.17 6.13 years .\nthe mean age between the people with hyperprolactinemia and the people without hyperprolactinemia did not show a significant difference ( p = 0.914 ) .\nhyperprolactinemia was found in two patients with galactorrhoea ( 8% ) , three patients with androgenic alopecia ( 12% ) , five patients with androgenic alopecia ( 12% ) , five patients with the history of ovary cyst ( 20% ) , one patient receiving drug for infertility ( among 115 married women ) , and 15 patients with positive family history of hirsutism .\nthere was no significant difference between these cases and hyperprolactinemia , but there was a significant difference between regular menses and hyperprolactinemia [ table 1 ] . in general ,\nmeasurement of dhea - s level showed that 18 patients ( 9% ) had a serum level more than 340 g / ml , and there was hyperprolactinemia in two patients .\ntwenty - two patients ( 11% ) had hypothyroidism , and all of them underwent treatment .\nthyroid serum tests were normal in all treated cases , but three cases of these patients had hyperprolactinemia .\nafter measuring lh and fsh and calculating the ratio of lh to fsh , lh / fsh ratio was more than 3 in four patients who did not have hyperprolactinemia , and ovary lesions were not found in these four patients after performing ultrasonography .\ntestosterone level was abnormal in 62 patients ( 31% ) among whom 19 patients had hyperprolactinemia in 11 patients with high testosterone , dhea - s was high but they did not have hyperprolactinemia .\nhirsutism makes different problems for women due to the creation of hairs in some parts of the body which are visible . for this reason ,\nmany patients who refer to treat hirsutism are young women so that mean age of the studied people was 26.18 6.05 in this study , and most patients were in age group of 2125 years .\nthe mean term of affliction with hirsutism in the studied people was 4.96 3.75 years .\nsimilar to our study , the patients with hirsutism are young women in similar studies . in a study by farnaghi et al . , which investigated 110 patients with hyperprolactinemia in the razi hospital of tehran , mean age of the patients was 29.7 3.2 years with an age range of 1638 years .\nthe term of affliction with hirsutism was 8 months to 7 years with the mean age of 4.2 1.2 years .\nin the study by tirgar - tabari et al . , most patients ( 70.1% ) were in age group of 2023 years . in the study by rahimnejad et al . in southern iran ,\nwhich 81 patients with hirsutism were studied , mean age was 22.5 0.5 years ( between 13 and 41 years ) .\nconsidering that one of the symptoms of endogenous glands diseases particularly ovary diseases is irregular menses , irregular menses was also investigated in this study . in our study ,\n, 38% in study by tirgar - tabari , 23.4% in study by yazdanfar et al . , 19.8% in study by ghaderi et al . ,\nand 52% in study by rahimnejad et al . difference in the reported percent can be attributed to other diseases and racial and hereditary causes . in our study , 60% of the patients had a positive family record in the first degree relatives in terms of affliction with hirsutism .\nin different studies , different percent have been reported in terms of positive family record among people with hirsutism .\na positive family record of hirsutism was found in 29% of patients in study by farnaghi et al .\n, 28% of patients in study by tirgar - tabari , 72.8% in study by rahimnejad et al . , 40.7% in study by yazdanfar et al . , and\nconsidering high positive family record in our study , it can be said that genetic has played an effective role in hirsutism .\nit should be considered that there is a strong family relation in some endogenous glands such as pcos or adrenal congenital hyperplasia one of which is hirsutism . in this study , 9% of the patients had galactorrhoea , 22.5% had androgenic alopecia , and 14.5% had ovary cyst record . moreover\n, 23 out of 115 married patients ( 20% ) underwent pharmacotherapy due to infertility . in a study by tirgar - tabari et al .\nlow rate of androgenic alopecia in our study can be due to the exclusion of the patients with pco because androgenic alopecia is one of the manifestations of pcos syndrome . in our study , 25 patients ( 12.5% ) had hyperprolactinemia .\nhyperprolactinemia was found in two patients ( 8% ) with galactorrhoea , three patients ( 12% ) with androgenic alopecia , five patients ( 20% ) with a history of ovary cyst , one patient receiving the drug for infertility ( 115 married women ) and 15 patients with a positive family record of hirsutism . there was a significant difference between menstrual disorder and hyperprolactinemia .\ncomparison of mean age between the people with hyperprolactinemia and the people without hyperprolactinemia and comparison of the mean term of affliction with hirsutism between the people with hyperprolactinemia and the people without hyperprolactinemia did not show a significant difference .\nhyperprolactinemia was 12.5% in our study , 22.8% in the study by ahmad et al .\n, 0.3% in the study by azziz et al . , 0% in the study by carmina et al . , and\nthe important point of our study is that the patients with pcos , which may be accompanied by hyperprolactinemia , were excluded from the study unlike other studies so that high prl level is not be a confounding factor due to affliction with pco .\nprolactinoma is the most prevalent pituitary gland tumor which secrets high amount of prl and can cause hirsutism , infertility , galactorrhoea , acne , and headache .\npituitary gland tumors should be considered in the people with high prl . although increase in the concentration of blood prl can be due to pregnancy , primary hypothyroidism , intake of some drugs ( chlorpromazine , perphenazine , haloperidol , metoclopramide , alpha methyldopa , resertin , opioids , amitriptyline , fluoxetine , verapamil , estrogen , and antiandrogen ) and pcos .\nin our study , despite the exclusion of patients with pco , the prevalence of hyperprolactinemia was high .\ntherefore , high serum prl level should be considered in the referring people with hirsutism .\nconsidering the importance of hyperprolactinemia as one of the causes of infertility and unawareness of patients with hirsutism , the hirsute patients particularly those with a positive family record of hirsutism are recommended to inform the physician and necessary studies should be conducted in this regard .\nthe present work was supported by a grant from the babol university of medical sciences . no additional external funding received for this study .\nthe present work was supported by a grant from the babol university of medical sciences . no additional external funding received for this study .", "answer": "background : hirsutism is one of the most important diseases that lead women to refer to dermatology clinic . \n hyperprolactinemia is one of the causes of hirsutism . \n the aim of this study was to determine prolactin ( prl ) levels in hirsute women.materials and methods : in this cross - sectional study , hirsute patients were evaluated . \n for all of the patients , 2 or 3 days after mense starting , hormone level tests were performed , and 200 patients that had not polycystic ovary syndrome enrolled to the study . \n a questionnaire of history and physical examination were performed . \n data have been analyzed with spss version 21.results:hyperprolactinemia were seen in 25 patients ( 12.5% ) . \n there was no significant relation between marital statuses , galactorrhoea , positive family history , and infertility with hyperprolactinemia . \n but significant relation was seen between irregular mense and hyperprolactinemia.conclusion:although hyperprolactinemia is the rare cause of hirsutism , the prevalence of hyperprolactinemia was high in our study . \n thus , prl level in hirsute patients should be evaluate .", "id": 523} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbulking agent injection is now a standard treatment for patients with grade 1 - 3 primary vesicoureteral reflux ( vur ) .\npatients with higher grades and secondary types of vur show an unacceptably high failure rate when treated with injections of a bulking agent .\ncollagen has been used for many years as a bulking agent in ureterovesical orifice and bladder neck to treat vur and incontinence .\ncollagen , however , can get calcified in the tissue , a process that can cause a series of problems for patients .\nwe present a case of a patient in whom calcified injected collagen showed imaging features mimicking ureteral stone .\na 15-year - old girl presented with moderate degree of right flank pain for 2 weeks .\npain was localized on the right side , altered with change in position , and did not relate to any particular organ .\nthe patient had been treated successfully for bilateral grade 2 vur when she was 3 years old .\na kidney ureter bladder ( kub ) radiography was requested and the report indicated presence of bilateral ureteral stone [ figure 1 ] .\nultrasonography showed bilateral ureterovesical junction ( uvj ) stone and mild stasis in both kidneys , which was compatible with the findings of the non - enhanced spiral abdomino - pelvic computed tomography ( ct ) scan [ figure 2 ] .\nhowever , diethylene triamine pentaacaetic acid ( dtpa ) scan with furosemide injection and radionuclide cystography ( rnc ) scan ruled out obstruction and relapse of vur .\ncalcification of bilateral intravesical collagen injected to treat her vur 12 years earlier was responsible for the positive findings on kub , ultrasonography , and spiral ct .\n15-year - old female with bilateral flank pain , which was suspected to be due to stones in bilateral ureterovesical junction , later diagnosed as due to calcification of collagen used 12 years earlier to treat vesicoureteral reflux .\n15-year - old female with bilateral flank pain , which was suspected to be due to stones in bilateral ureterovesical junction , later diagnosed as due to calcification of collagen used 12 years earlier to treat vesicoureteral reflux .\nspiral ct scan of pelvis without intravenous and oral contrast shows bilateral uvj calcifications ( arrows ) .\nendoscopic therapy for vur has gained popularity because of elimination of invasive surgical procedures in children .\nin addition , it has an acceptable success rate and a low level of complications . although a transition has occurred in the material of choice from teflon to collagen and now to hyaluronic acid copolymers .\nhowever , we do find patients who were treated with collagen now in the second decade of their life .\nthe injected material , being a foreign body , can induce inflammatory response that leads to tissue calcification .\nthis calcification has been reported to be symptomatic with some patients reporting episodes of stone passing , hematuria , and even obstruction .\nthis is the second case report of ureterovesical injection calcification presenting as a ureteral stone during differential diagnosis and the first report of its imaging .\nunlike the first case report where the patient presented with renal colic and passing of stone , our patient was completely asymptomatic , except for positional non - related flank pain .\nthere is no difference between a ureteral stone and calcification of injected collagen , when viewed by different imaging modalities like kub [ figure 1 ] , ct scanning [ figure 2 ] , and also ultrasound examination .\nthis similarity is because of the place where the bulking agent is injected . in doubtful cases , as in our case , uvj obstruction can be ruled out by dtpa nuclear scan in which glomerular filtration of injected nuclear radioisotope reveals any obstruction in the upper urinary tract .\nthe diagnosis of uvj stone in the presence of uvj calcification , possibility of ureteral stone passing ( in a patient with renal colic ) after uvj injection therapy , and the probability of recurrent vur after ureteral intervention ( in which calcified ureteral orifice will tolerate dilatation to pass the ureteroscope ) remain to be studied .\nvur can be assessed by rnc in which a radioisotope passing to the bladder via the urethral catheter reveals presence of vur .\nthe standard treatment for grade 1 and 3 primary vur is injection of a bulking agent into the uvj .\nclinicians should be aware that calcification of bulking agent like collagen can occur and they need to differentiate this from ureterovesical stones on imaging findings .", "answer": "primary vesicoureteral reflux can be treated by injection of a bulking agent into the wall of the ureterovesical junction . over time , the bulking agent can get calcified . \n radiological images of the area show findings that mimic those seen in ureterovesical junction calculi . in this report \n , we present the imaging findings of this phenomenon and discuss its challenging aspects .", "id": 524} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 53-year - old asian woman with a history of lupus erythematosus was initially treated with hydroxychloroquine ( plaquenil , unknown dose ) for 5 years .\napproximately 3 years ago , the patient 's medication was changed to chloroquine ( 400 mg daily ) . within a few years of taking chloroquine\n, she noticed a circular shadow in her central vision , which she described as an arch surrounding her central vision . at first\n, she only noticed a superiorly oriented half - moon shadow that lasted for a few seconds during reading .\nthe shadow was seen while both eyes were open and disappeared after a few seconds . because of these symptoms and the presence of bull 's eye maculopathy on fundus examination , chloroquine was discontinued and the patient 's medication was changed to dapsone ( unknown dose ) .\nthe best - corrected visual acuity ( corrected with current spectacles ) of the highly myopic patient during her most recent examination was 20 / 25 in both eyes , with no evidence of an afferent pupillary defect .\nslit - lamp examination indicated that the anterior segment was unremarkable and goldmann applanation intraocular pressure was normal ( 16 mmhg ) in both eyes .\nhowever , a significant central defect was noted on humphrey visual field ( hvf ) examination ( humphrey visual field analyzer 10 - 2 ; humphrey instruments , san leandro , ca , usa ) in both eyes . dilated fundoscopy revealed tilting of the optic nerves in both eyes , consistent with myopia , and a ring - shaped area of rpe depigmentation in the parafoveal area of the left eye ( fig .\nfundus autofluorescence ( faf ) imaging revealed a hypofluorescent lesion in the foveal and perifoveal areas correspond with the bull 's eye retinopathy . in the left eye ,\na prominent hypofluorescent lesion was also noticed on faf imaging , reflecting marked atrophy of the rpe layer ( fig .\ncross - sectional retinal scans , obtained with sd - oct ( spectralis hra+oct ; heidelberg engineering , heidelberg , germany ) showed obvious thinning of the macula and disruptions in the outer retina .\nmore specifically , loss of the photoreceptor inner / outer segment ( is / os ) junction corresponded to the location of the maculopathy as identified on fundus photography , faf , and hvf 10 - 2 .\nthe outer retinal layer had a moth - eaten appearance at the is / os junction , but the thickness and appearance of the inner retina were within normal limits .\nadditionally , a downward displacement of the overlying retina was seen in perifoveal areas and corresponded to the hypofluorescent lesion in faf images . unlike the anatomically disrupted areas , which corresponded to the bull 's eye lesion , the central fovea had normal thickness and structure on sd - oct in both eyes ( fig .\nthe ao system used in the current study utilized a dual liquid crystal on silicon spatial light modulators ( lcos - slms ; x10468 - 02 , hamamatsu photonics , morimoto , japan ) first introduced by hirose et al . .\nalthough deformable mirrors have been widely used , their performance is limited with respect to compensating large amounts of aberration of human eyes . meanwhile , although lcos - slm is able to compensate large amounts of aberration by the phase wrapping method utilizing a continuity of the wavefront of a laser beam , it is only capable of compensating a particular polarization component .\nthis system is very efficient at following changes in aberration of a subject according to change in imaging location , but is not suitable for obtaining high contrast images because the power of the lights used for simultaneous imaging and measurement / compensation of time is limited for safety . in this study\n, we overcame these problems by adopting dual lcos - slm to compensate the two orthogonal polarization components and sequential processing of slo imaging and measurement / compensation of aberrations .\nao - slo images were obtained and cone density was measured 0.5 , 1.0 , and 1.5 mm from the center of the fovea in each of the 4 major directions ( superior , inferior , nasal , and temporal ) .\na montage was then created and verified by checking the correspondence between the ao - slo and wide - field images .\ncone density was calculated using photoreceptor analysis software ( canon , tokyo , japan ) . to obtain an accurate cone density ,\nthe axial length , anterior chamber depth , and keratometry values were all considered when counting cone cells , which were represented in images as bright spots 2 to 5 m in size .\nwe manually selected areas of interest , and excluded retinal vessels and artifacts that obscured the underlying cone mosaic .\nao - slo images showed patch cone mosaic lesions , indicating abnormal regions of missing or lost cones .\nin addition , the observed cones were asymmetrical in shape and size and varied in brightness ( fig .\ncone densities in the right eye were 14,927 , 10,377 , and 11,853 cones / mm at 0.5 , 1.0 , and 1.5 mm from the center of the fovea , respectively .\nthe corresponding cone densities in the left eye were 16,692 , 12,564 , and 13,100 cones / mm , respectively .\nthe cone density at 1.5 mm from the center of the fovea was closer to normal than the other distances ; however , the photoreceptors located 1.5 mm from the foveal center exhibited asymmetrical shapes and sizes , and varied in brightness in ao - slo images .\nadditionally , sd - oct images showed an abnormal is / os cytoarchitecture 1.5 mm from the foveal center .\nwhen we matched the disrupted areas on the ao - slo images with the visual field test , the areas with abnormal cone mosaic patterns and low cone density corresponded with the location of visual field defects on hvf ( fig .\nocular side effects associated with chloroquine can be primarily divided into keratopathy , ciliary body changes , and retinopathy .\nbull 's eye maculopathy , a type of retinopathy , is associated with the use of antimalarial agents and is relatively rare . however , bull 's eye maculopathy is the most serious of the ocular adverse effects and is of serious pathologic concern , as the associated visual changes can be severe and there is little chance of visual recovery .\nin addition , visual loss associated with bull 's eye maculopathy can progress even after the drug treatment is terminated .\npatients with retinopathy usually present with central visual loss , visual field defect , color vision deficiency , photoaversion , night blindness , and entopic phenomenon .\neasterbrook reported that patients with minimal paracentral scotomas do not complain of symptoms and have normal color vision . in these patients ,\nhowever , in nearly 70% of patients with ocular symptoms , abnormal color vision , and fundus changes , retinopathy progresses even after termination of drug use . together\n, these studies illustrate the importance of early detection , ideally before the onset of visual symptoms .\nfluorescein angiography ( fa ) can reveal the bull 's eye pattern of granular hyperfluorescence , but is not useful for the diagnosis of early retinopathy .\nin full - field electroretinography ( erg ) , there may be a deepening of the a - wave or an amplitude reduction in the scotopic b - wave .\nhowever , in most cases , erg findings are normal with minimal macular damage and decrease only after diffuse retinal damage has occurred .\nit was also reported that sd - oct images are able to show the perifoveal interruption of the photoreceptor is / os junction in eyes with chloroquine retinopathy . however , despite this new information , there is currently no established criteria for diagnosing chloroquine retinal toxicity prior to the development of irreversible visual loss .\nstudies performed in mice have shown that photoreceptors are the primary targets affected by chloroquine maculopathy , and that further degeneration occurs despite cessation of medication .\nadditionally , rosenthal et al . showed that use of chloroquine in rhesus monkeys causes significant changes in both the inner and outer retinal layers .\nexposure to ultraviolet radiation causes chloroquine to fluoresce , and based on this property , clinical studies have shown that a widespread , severe reduction of rod and cone processes occur in the outer nuclear and plexiform layers . still , because of aberrations of ocular optics , none of the currently available imaging methods are capable of observing cells with disrupted photoreceptors in living human eyes . recently\n, ao technology has been developed that allows for individual cones to be clearly visualized in vivo by compensating for aberrations in ocular optics [ 6 - 8 ] . using ao - slo technology ,\nseveral studies have shown that successful visualization of photoreceptor microstructure is possible in both normal eyes and eyes with various retinal diseases .\nconsistent with previous ao studies , our ao - slo images from normal eyes showed a regular cone mosaic pattern , in which the cone density decreased with increasing distance from the center of the fovea . in the patient with bull 's eye maculopathy , we observed a disrupted cone mosaic pattern with individual cones having irregular shapes and sizes .\nadditionally , compared with normal patients , patients with bull 's eye maculopathy can exhibit irregular cone brightness as well as dark and patchy lesions where cones are either missing or lost . in the present study , along with the disrupted cone mosaic pattern , measured cone densities were diminished in all areas . to better interpret the findings in our study , comparative data was obtained from both previous studies and historical controls . in normal eyes\nthe average cone densities 0.5 and 1.0 mm away from the foveal center are approximately 30,000 and 15,000 cones / mm , respectively .\nthese values were in agreement with histological studies reporting cone densities of 37,000 , 16,000 , and 14,000 cones / mm at 0.5 , 1.0 , and 1.5 mm away from the foveal center , respectively .\nstepien et al . previously reported an ao image of bull 's eye maculopathy associated with antimalarial agent use .\nalthough similar abnormal images of cones have been obtained using their ao system , they were not as high quality as the images obtained in the present study .\nspecifically , we were able to achieve improved image quality and contrast because our ao - slo utilized a dual liquid crystal on lcos - slms to correct for wavefront aberrations , while the system used by stepien et al . \nmoreover , creating a montage of ao - slo images made it possible to compare each ao - slo image to visual field test results . using this technique , we were able to demonstrate that areas with visual defects could be matched with cone pattern and density abnormalities .\nbecause ao - slo can image the retina with such high resolution , it is more sensitive to photoreceptor abnormalities than sd - oct . in our study\n, sd - oct images revealed equal disruption of the outer retinal layer at 1.0 and 1.5 mm away from the fovea .\nhowever , ao - slo images revealed a higher level of cone pattern disruption and a lower cone density at 1.0 mm away from the fovea , compared with 1.5 mm away from the fovea .\nthere were several limitations of the present study that should be mentioned . because the central foveal structure was conserved , our patient had a visual acuity of 20 / 25 .\nhowever , we could not obtain images of the central fovea for reasons described in previous studies [ 6 - 8 ] .\nunfortunately , the inability to obtain these images made it impossible to compare cellular images of the fovea with those obtained from the bull 's eye lesion .\nanother limitation of our study was that the ao - slo system could not acquire images from the central fovea or the peripheral retina .\ntherefore , we only investigated cone properties at 0.5 , 1.0 , and 1.5 mm away from the center of the fovea .\nbecause of this limitation , we were unable to compare preserved areas adjacent to the bull 's eye lesion , which may possibly have contained cones in the preclinical stage of the disease . as described above , the visual acuity of the patient was 20 / 25 , and we hypothesized that the reason for the relatively mild visual decrease was because the structure of the central fovea remained relatively preserved .\nhowever , we could not confirm this possibility because the center of the fovea could not be precisely imaged by ao - slo .\nsimilarly , because the ao - slo can not obtain images from the peripheral retina , it was not possible to compare the disrupted macula to the relatively preserved peripheral retina .\ndepending on the specific disease , patients may be treated with either a chronic maintenance or acute high - level dose of chloroquine . a daily dose of chloroquine > 3 mg / kg and a treatment duration of > 5 years\ntherefore , patients who are taking chloroquine or hydroxychloroquine should have regular ophthalmic examinations to detect retinal changes as early as possible in order to minimize retinal toxicity . in the present study\n, we showed that ao - slo can image cellular structures of the retina in living eyes in order to detect preclinical stages of chloroquine associated retinal damage that may not be apparent on standard clinical tests ( e.g. , fundus photography , fa , hvf , and electrophysiological testing ) .\nimportantly , the ability to identify photoreceptor disruptions in the preclinical stages of toxicity should allow for chloroquine withdrawal during the reversible stages of maculopathy . despite the limitations of our ao system\n, our results suggest that ao - slo should provide a non - invasive , quantitative , high - resolution modality for imaging chloroquine retinopathy patients .\nlikewise , the abilities of ao - slo have the potential to provide a new approach for the diagnosis and monitoring of chloroquine toxicity .", "answer": "a 53-year - old asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus . within a few years \n , she noticed circle - shaped shadows in her central vision . upon examination , \n the patient 's visual acuity was 20 / 25 in both eyes . \n humphrey visual field ( hvf ) testing revealed a central visual defect , and fundoscopy showed a ring - shaped area of parafoveal retinal pigment epithelium depigmentation . \n fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull 's eye retinopathy . \n adaptive optics scanning laser ophthalmoscope ( ao - slo ) revealed patch cone mosaic lesions , in which cones were missing or lost . \n in addition , the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness . unlike previous studies employing deformable mirrors for wavefront aberration correction , our ao - slo approach utilized dual liquid crystal on silicon spatial light modulators . \n thus , by using ao - slo , we were able to create a photographic montage consisting of high quality images . \n disrupted cone ao - slo images were matched with visual field test results and functional deficits were associated with a precise location on the montage , which allowed correlation of histological findings with functional changes determined by hvf . \n we also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral - domain optical coherence tomography .", "id": 525} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nventral hernias are the second most common type of abdominal wall hernias , after inguinal hernias .\nthe majority of ventral hernias are incisional , occurring in 3% to 13% of laparotomy incisions , necessitating approximately 90 000 ventral hernia operations per year .\nthe use of prosthetic material , such as polypropylene mesh , polytetrafluoroethylene , and marlex mesh has decreased rates of recurrence . however , wound complications with the use of mesh in open ventral hernia repair are significant . since 1992\n, the laparoscopic technique has been applied to the repair of ventral hernias because of its many advantages including the absence of large subcutaneous flaps , a lower incidence of wound infection , and a reduction in postoperative pain and hospital stay .\nthe lower recurrence rates are most likely due to the tension - free and intraperitoneal placement of the mesh .\nlaparoscopy offers a clear view of the entire fascial defect , which is not always possible with the open technique , especially if a \nthus , the entire defect is completely circumscribed with the laparoscopic technique . the surgical technique described for laparoscopic ventral hernia repair varies by surgeon\n. however , all techniques reported use at least 3 port sites , with one or more being 10 mm . using this technique , either the primary surgeon or the first assistant is working in mirror - image .\nbetween july 2002 and january of 2003 , 3 patients underwent laparoscopic ventral hernia repair with mesh in which only two 5-mm ports were used for small incisional or ventral hernias .\nfollow - up surveillance for complications and hernia recurrence was performed in the immediate postoperative period , 1 week to 2 weeks after surgery .\nadditional follow - up was obtained by telephone interview 6 months to 12 months postoperatively .\nafter the abdomen was prepped , an iodine impregnated adhesive drape dressing was placed on the patients ' abdomen .\naccess to the abdomen was obtained in an area lateral to the hernia by using a veress needle .\nafter exploration of the abdomen , a second 5-mm trocar was introduced under direct visualization on the opposite side of the fascial defect .\nadhesiolysis was performed to free the anterior abdominal wall , and the margins of the hernia defect were circumferentially cleared to a distance of at least 4 cm .\na dual , expanded polytetrafluoroethylene ( eptfe ) mesh ( dualmesh , wl gore , flagstaff , az ) was used , ranging in size from 8.5 cm to 10 cm .\nonce the mesh was place intracorporeally , the sutures were retrieved through the abdominal wall by using a laparoscopic suture passer .\nthe sutures were tied extracorporeally , and the knots were buried in the subcutaneous tissues .\nthe circumference of the mesh was then affixed , by using a 5-mm spiral tacking device , to the posterior abdominal wall at intervals of approximately 1 cm .\nafter the abdomen was prepped , an iodine impregnated adhesive drape dressing was placed on the patients ' abdomen .\naccess to the abdomen was obtained in an area lateral to the hernia by using a veress needle .\nafter exploration of the abdomen , a second 5-mm trocar was introduced under direct visualization on the opposite side of the fascial defect .\nadhesiolysis was performed to free the anterior abdominal wall , and the margins of the hernia defect were circumferentially cleared to a distance of at least 4 cm .\na dual , expanded polytetrafluoroethylene ( eptfe ) mesh ( dualmesh , wl gore , flagstaff , az ) was used , ranging in size from 8.5 cm to 10 cm .\nonce the mesh was place intracorporeally , the sutures were retrieved through the abdominal wall by using a laparoscopic suture passer .\nthe sutures were tied extracorporeally , and the knots were buried in the subcutaneous tissues .\nthe circumference of the mesh was then affixed , by using a 5-mm spiral tacking device , to the posterior abdominal wall at intervals of approximately 1 cm .\nthe size of the mesh used varied , based on the size of the original defect .\nadditionally , no recurrences were noted after a mean follow - up of 9 months ( range , 6 to 12 ) .\nlaparoscopic ventral hernia repair is a procedure that has gained acceptance among surgeons and patients over the last 5 years to 10 years\n. the documented advantages of laparoscopic surgery in general include faster recovery and return to normal activity , less postoperative pain , fewer wound - related complications , and a better cosmetic result .\nin addition , the intraperitoneal repair performed laparoscopically poses a significant mechanical advantage and is associated with less recurrence .\nwe present 3 patients who underwent laparoscopic repair of a ventral hernia in which two 5-mm ports were used .\nthese patients had no surgical complications , and the mean operating room times were acceptable .\nthis technique offers all the advantages inherent to laparoscopic surgery , with the added benefit of the use of only two 5-mm ports .\nlaparoscopic repair of ventral or incisional hernias can be performed using only two 5-mm ports .\nthis technique can be done on an outpatient basis in a safe , timely fashion .", "answer": "objective : high recurrence rates have been documented after primary repair of incisional hernias . \n laparoscopic ventral and incisional hernia repairs have been performed with very low rates of recurrence . \n we have modified the standard technique of laparoscopic repair in patients with small incisional and ventral hernias . \n the purpose of this study was to document the technique utilizing only two 5-mm ports and demonstrate that it is safe , effective , and feasible.methods:three patients with small incisional or ventral hernias were examined . \n the standard laparoscopic ventral hernia repair technique was modified as follows : two 5-mm ports were inserted on opposite sides of the defect . \n the defects ranged from 2.5 cm to 4 cm in size . \n expanded polytetrafluoroethylene mesh ( dualmesh , wl gore , flagstaff , az ) was used to cover the hernia defect , overlapping the defect margins circumferentially by 3 cm . \n the mesh diameter ranged from 8.5 cm to 10 cm . \n the mesh was inserted through a 5-mm skin incision site and affixed into position with transfascial sutures and spiral tacks.results:the operative time ranged from 53 minutes to 57 minutes . \n all patients were discharged home the day of surgery and reported minimal postoperative pain . \n follow - up ranged from 6 months to 1 year ; all patients were doing well without recurrence.conclusion:laparoscopic repair of ventral or incisional hernias can be performed using only two 5-mm ports . \n this technique can be done on an outpatient basis in a safe , timely fashion .", "id": 526} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npharmaceutical companies and many academic centers have thousands of high - quality compounds that represent potential new drugs .\nthese high - quality compound collections contain thoroughly studied development candidates and , in many cases , old drugs that were generated for non - cns disorders but that might be useful therapies for one or more psychiatric diseases . however , testing these compounds for activity relevant to treating psychiatric diseases is challenging . whereas some disease areas , such as cancer or infectious disease , are relatively amenable to high - throughput in vitro testing of hundreds of thousands of compounds , psychiatric diseases are not . because psychiatric diseases generally result from disorders of cell cell communication or circuitry , intact systems are required to detect improvement in disease - relevant endpoints .\nthe need for observers to be blinded to the treatment group of each animal increases the resources required to appropriately dose and randomize animals in a way that is invisible to the observer .\nfurthermore , multiple complementary behavioral assays are required to determine whether observed effects are robust and are not due to undesired effects , such as sedation ( crawley and paylor , 1997 ) .\nthus , the discovery of new neuropharmacological drugs with novel mechanisms of action is impeded by the absence of high - throughput , robust , and objective behavioral assays . very recently a 96-well behavioral assay measuring the photomotor response of zebrafish embryos demonstrated that different classes of neuropharmacological compounds cause distinct patterns of responses ( kokel et al . , 2010 ) .\nsuch an assay is relatively inexpensive and is well suited to screening high numbers of compounds about which little is known . for high - quality compounds , particularly compounds that have entered human testing , a rodent system offers advantages .\nfor advanced compounds , rodent pharmacokinetics and safety are often known , and sufficient quantities of these compounds generally exist to support rodent studies . to enable testing of many compounds for behavioral effects relevant to psychiatric disease\n, psychogenics developed smartcube , an automated system in which behaviors of compound - treated mice are captured by digital video and analyzed with computer algorithms ( brunner et al . , 2002 ) .\npgi analytical systems uses data from smartcube to compare the behavioral signature of a test compound to a database of behavioral signatures obtained using a large set of diverse reference compounds . in this way ,\nthe neuropharmacological effects of a test compound can be predicted by similarity to major classes of compounds , such as antipsychotics , anxiolytics , and antidepressants .\nthis approach is ideally suited to screening collections of existing drugs or drug candidates for previously unknown neuropharmacology , which could expedite the development of new and unexpected treatments for psychiatric disorders . in this paper , we demonstrate that this system can detect relevant cns activity of compounds representing mechanisms beyond those used clinically to treat psychiatric disorders .\nan overview of pgi analytical systems , a rapid , computer vision - enabled murine screening system for neuropharmacological activity , is shown in figure 1 . the pgi analytical systems training set consisted of hundreds of doses of clinically approved reference drugs , grouped per indication ( e.g. , anxiolytics , antidepressants , etc . ) .\ndrugs were injected 15 min before the test , and multiple challenges were presented over the course of the test session .\ndigital videos of the subjects were processed with computer vision algorithms to extract over 2,000 dependent measures including frequency and duration of behavioral states such as grooming , rearing , etc . , and many other features obtained during the test session .\npgi analytical systems combine proprietary hardware , robotics , computer vision , and data mining techniques to collect thousands of behavioral features in a single test session and extract unique signatures for each compound .\nthese signatures are compared with the signatures obtained from reference compounds ( shown to have clinical efficacy ) in different therapeutic classes and subclasses to predict clinical utility .\na proprietary machine learning algorithm was developed to train a probabilistic classifier that mapped the extracted computer vision feature values from the training set to their corresponding cns indications .\nthis tool was used to establish a reference database of therapeutic class signatures and provided a mechanism to determine the cns probabilistic profile of an arbitrary test sample .\nour reference database comprises 14 classes of drugs with some of the major classes , such as the antidepressant class , comprising several subclasses with representatives of most of the drugs in the market .\ntest set assessment were chosen from our evaluation tests and two separate types of classifiers were built that make independent predictions : one at the therapeutic class level and one at the level of highly performing subclasses .\nthe behavioral signatures of the test drugs were scored by these classifiers to predict potential therapeutic utility . to evaluate the ability of the pgi analytical system to detect relevant behavioral responses to novel compounds ,\nwe tested two compounds that represent mechanisms not yet used clinically to treat psychiatric disorders but that impact relevant behavioral endpoints in rodents .\nthe two test compounds , tp-10 and pf-670462 , had not been included in the computer algorithm training set .\ntp-10 is a sub - nanomolar inhibitor of pde10a , a dual - substrate phosphodiesterase expressed in medium spiny neurons of the striatum that regulates striatal output by regulating both camp and cgmp hydrolysis ( strick et al . , 2007 ) .\ntp-10 demonstrates multiple behavioral effects in rodents that are consistent with clinically effective antipsychotics , including decreased locomotor activity , inhibition of conditioned avoidance response , and improvement of amphetamine - induced deficits in auditory gating ( schmidt et al . , 2008 ) .\npf-670462 is a casein kinase i ( ck1 ) inhibitor ( badura et al . , 2007 ) .\nall compounds were dissolved in a pharmasolve , peg , pg mixture , and were injected i.p .\n13 h before the behavioral test because of its known effects on circadian rhythm at 50 mg / kg s.c .\n( badura et al . , 2007 ) ; this procedure was done both in the morning and evening . as a follow - up test to confirm the anxiolytic signature of pf-670462 we use the marble burying test .\npf-670462 was dissolved in 40% cyclodextrin and injected at 10 and 30 mg / kg , s.c .\nexperimenters were blind to the mechanisms of action of both compounds and to the dose being used . the institutional animal care and use committee of psychogenics reviewed and approved the animal use in these studies . the animal care and use program is fully accredited by the association for assessment and accreditation of laboratory animal care , international .\nin the pgi analytical system , tp-10 produced a dose - dependent signature of activity most similar to that of known antipsychotics , particularly at the 1-mg / kg dose ( figure 2 ) .\nresponse curve in this system , consistent with its steep dose response curve in other rodent models ( schmidt et al . , 2008 ) . at the lower 0.5 mg / kg dose , tp-10 s activity is more similar to that of the vehicle than to any class of drugs in the reference database . at the higher dose of 2 \nmg / kg , tp-10 produced a behavioral pattern that is quite different from that of the vehicle yet not specific to any one class .\nnotably , tp-10 activity at the 2-mg / kg dose has a large behavioral component similar to that of high - dose antidepressants but not medium - dose antidepressants .\ninterestingly , three of the four reference antipsychotic signatures shown in figure 3 also have a larger high - dose antidepressant - like component at their highest doses .\noverall , the profile of tp-10 in this computer - aided screening system is similar to that of clinically used antipsychotic drugs ( gleason and shannon , 1997 ; powell et al . , 2008 ;\nthis observation is consistent with tp-10 s activity in multiple rodent models ( schmidt et al . , 2008 ) , suggesting that the pgi analytical systems can identify antipsychotic - like activity of compounds acting through novel mechanisms . the pde10a inhibitor tp-10 produced a signature of activity suggesting potential antipsychotic activity .\nthe size of a given colored region on each bar indicates the probability that the activity of tp-10 at that dose matches a given class of neuropharmacological agents .\nthe size of the white area represents that probability that the activity is more similar to that of the vehicle rather than to that of any compounds in the reference database .\ndrug signatures of four of the antipsychotic drugs included in the reference dataset : aripiprazole , clozapine , haloperidol , and olanzapine .\nin contrast to pde10a , for which considerable literature data support its role as an antipsychotic target , the potential usefulness of altering ck1 s effects on circadian rhythm for treating psychiatric disorders is unknown .\nck1 is an important regulator of period proteins ( per ) that regulate the clock mechanism in cells ( lee et al . , 2001 ) . clearly , improved regulation of circadian rhythm could improve functioning in patients with sleep disorders .\nfurthermore , disruptions of the sleep wake cycle can affect cognition , memory , and mood ( benca et al .\nck1 is also involved in darp32 phosphorylation and thus participates in dopamine - dependent behavioral activation ( bryant et al . ,\nthus , the ck1 mechanism is a good candidate for screening in a system that may identify behavioral signatures relevant to a wide variety of psychiatric disorders . in the pgi analytical system at intermediate doses of 30 and 50 \nmg / kg , the ck1 inhibitor pf-670462 ( badura et al . , 2007 ) demonstrated a signature consistent with anxiolytic , but not sedative / hypnotic , activity ( figure 4 ) . because pf-670462 produces changes in circadian rhythm ( badura et al . , 2007 ) , we tested whether administering pf-670462 to mice 13 h prior to testing might produce a more relevant behavioral signature .\ninterestingly , the compound had almost no detectable behavioral effects in this system when dosed 13 h before testing , either in the morning ( 5:30 am ) or the afternoon ( 7 pm ) . the anxiolytic signature of pf-670462 seen at the 30 , but not 10 , mg / kg dose was confirmed in the marble burying test , in which the higher dose decreased marbles buried without a decrease in locomotion ( figure 5 ) .\nthe ck1 inhibitor pf-670462 demonstrated a signature consistent with anxiolytic activity ( yellow ) and , at the highest dose tested , behavioral effects similar to that of opiate analgesics ( pink ) , although this dose is higher that doses tested previously in rodents and may reflect non - specific effects .\n15 min before the test in studies represented by the five left - most bars of the chart . to assess\npotentially delayed behavioral effects due to its effects on circadian rhythm , pf-670462 was injected s.c .\n13 h before testing in the morning ( am ) or in the afternoon ( pm ) .\nthe ck1 inhibitor pf-670462 shows anxiolytic activity in the marble burying test with a strong yet non - significant trend at 10 mg / kg and a significant effect at 30 mg / kg , consistent with the dose \nresponse anxiolytic signature uncovered by the high - throughput screen [ anova f(4,43 ) > 8.8 ,\np < 0.0001 ; fisher plsd p < 0.02 ] . the drug was injected s.c .\nour work demonstrates the usefulness of a computer vision - based system for identifying behavioral effects of novel compounds and mechanisms in a relatively high - throughput in vivo assay .\nas one example , the pde10a inhibitor tp-10 demonstrated a behavioral signature in the pgi analytical system that was more similar to that of known antipsychotics than to that of other classes of neuropharmacological agents .\nalthough the efficacy of pde10a inhibition in humans has not been tested , the activity of tp-10 here is consistent with effects of clinically used antipsychotics in multiple rat in vivo assays ( schmidt et al . , 2008 ) .\nimportantly , the steep dose response curve of tp-10 was also consistent between the computer vision - based system and traditional rodent assays .\ninterestingly , tp-10 was ineffective in two mouse pre - pulse inhibition models ( schmidt et al . , 2008 ) , although it showed an antipsychotic - like signature in mice in the present study .\nthe computer vision - based system , which measures hundreds of small behavioral events , may reveal more relationships because of its ability to assess compound effects more broadly than a model designed to test one specific functional hypothesis .\nthe tp-10 behavioral signature at the highest dose tested suggested a small degree of activity similar to that of high - dose antidepressants .\nthis feature was observed with the higher doses of most of the four reference antipsychotics in figure 3 , as well , suggesting that the similarity is due to side effects caused by high doses of all such compounds .\nthe computer vision - based system also suggested new hypotheses regarding the behavioral effects of ck1 inhibition .\nwe found that moderate doses of pf-670462 produced activity similar to that of anxiolytic agents , but not sedative / hypnotics .\nwe followed up this result in the marble burying test , an assay predictive of anxiolytic therapeutic potential , and confirmed that a dose of 30 mg / kg has anxiolytic activity ( figure 5 ) . in summary ,\nour data demonstrate that the pgi analytics computer vision - based system rapidly detects relevant behavioral effects of compounds acting through new mechanisms .\nbecause the assay and data analysis are highly automated , use of the system eliminates the need for subjective human observation and evaluation of behavior , thus eliminating significant resource requirements along with much of the potential for bias inherent in subjective measurements .\nthis approach is ideally suited to screening libraries of existing drugs or drug candidates for previously unknown neuropharmacology , which could expedite the development of new and unexpected treatments for psychiatric disorders .", "answer": "the lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology . in vivo \n behavioral assays are more predictive of activity in human disorders , but such assays are often highly resource - intensive . here \n we describe the successful application of a computer vision - enabled system to identify potential neuropharmacological activity of two new mechanisms . \n the analytical system was trained using multiple drugs that are used clinically to treat depression , schizophrenia , anxiety , and other psychiatric or behavioral disorders . during blinded testing the pde10 inhibitor tp-10 produced a signature of activity suggesting potential antipsychotic activity . \n this finding is consistent with tp-10 s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs . \n the ck1 inhibitor pf-670462 produced a signature consistent with anxiolytic activity and , at the highest dose tested , behavioral effects similar to that of opiate analgesics . \n neither tp-10 nor pf-670462 was included in the training set . \n thus , computer vision - based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms .", "id": 527} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwho has estimated that there were 171 million people worldwide with diabetes mellitus ( dm ) in 2000 and predicted that 366 million people will have dm by 2030 .\nthe united states centers for disease control and prevention have estimated that 13 million persons in the united states have diagnosed dm , and an additional 5,2 million have the disease but it is not yet being diagnosed .\ndiabetes mellitus is a severe metabolic disease associated with a number of complications including retinopathy , nephropathy and neuropathy .\nmortality related to dm and its complications result in 3.8 million deaths annually , accounting for 6% of the total worldwide mortality [ 2 , 3 ] .\nthe mortality risk in the diabetic population in the age of 4049 years is about 67 years and for the age category of 6069 it is about 3 - 4 years higher , compared to mortality risk , at the same age healthy population .\nthe stage of nephropathy , including the severity of proteinuria is a predictable factor for the mortality risk .\napproximately 2.5% to 15% of annual healthcare budgets is spent on care of patients with diabetes and associated complications .\nit has been estimated that programs to identify and treat diabetic retinopathy ( dr ) would have saved the united states health care budget nearly 400 million dollars annually in the early 1990s , ] a figure that would probably be substantially higher today .\na lot of studies in dm type 2 between which is the ukpds - study , have underlined the beneficial effect of having the hba1c , not < 6% . a diverse array of micro- and macrovascular changes ,\nare induced trough bad metabolic memory and increase , as well as decrease of hba1c ( fig . 1 ) . \n\nincrease of glycated hemoglobin in diabetic population at baseline , and in 6 years follow - up period , has the same impact on the cardiovascular complications , as the decrease of hba1c < 6.0% accord \nincrease of glycated hemoglobin in diabetic population at baseline , and in 6 years follow - up period , has the same impact on the cardiovascular complications , as the decrease of hba1c < 6.0% retinal vascular changes in diabetic population are the most common cause of blindness among eye diseases .\nimpairment of retinal circulation results in blood flow alternations that affect the delivery of oxygen and metabolic substrates to the tissue .\nrelease of oxygen derived free radicals , nitric oxide - mediated neurotoxicity , and delayed cell death lead to neuronal damage . poor glycemic control sets the stage for initiation of the microvascular changes .\nthe molecular basis of dr and maculopathy takes into consideration the role of growth factors and cytokines in the development of diabetic vascular alterations , their specific influence on the cellular interaction between retinal endothelial cells and pericytes , and the role of intravascular blood components .\nthe earliest histological features of dr include neuroretinal damage , capillary basement membrane thickening , loss of pericytes and loss of endothelial cells .\nthe hallmark of proliferative diabetic retinopathy ( pdr ) is neovascularization ( nv ) which occurs at the latter stages of the disease and can result in blindness ; nv is the consequence of abnormal fibrovascular proliferations with subsequent bleeding and retinal detachment .\nnumerous studies have underlined the role of the angiogenic factors in the progression of dr and include vascular endothelial growth factor ( vegf ) , insuline - like growth factor ( igf-1 ) , hepatocyte growth factor ( hgf ) , basic fibroblast growth factor ( b - fgf ) , platelet - derived growth factor ( pdgf ) , pro / inflammatory cytokines and angiopoetins . on the other hand ,\nthe major antiangiogenic factors are : pigment epithelium derived factor ( pedf ) , transforming growth factor beta ( tgf - beta ) , thrombospondin ( tsp ) and somatostatin [ 57 ] .\nthe balance among angiogenic and antiangiogenic factors has a determining role in the progression of dr .\nthe early diabetic retinopathy study ( edrs ) demonstrates the ability of panretinal photocoagulation to reduce the rate of severe visual loss by 50% for eyes with high risk characteristics , defined as nv originating from optic disc ( > 1/3 disc diameter ) , any nv originating from the optic disc with hemorrhage , and nv originating from the retina with vitreous hemorrhage .\nthe edrs showed that patients with ( type 2 ) dm who were older than 40 years of age , with severe nonproliferative dr ( defined as hemorrhages in four quadrants , or intraretinal microvascular abnormalities in one quadrant ) , have benefited from early panretinal photocoagulation . the early vitrectomy diabetic study ( evds ) showed that early vitrectomy ( within 6 months of onset of vitreous haemorrhage ) was associated with better results in type 1 diabetes mellitus patients [ 79 ] .\nwhere are we now in relation to our knowledge in prevention and early treatment of dr ? did we follow our investigations in a direction that can give us solution of the main problems , or our investigations do not have a real clinical impact ?\ncan we expect better predictive strategies for early diagnosis and treatment ? to answer these questions we will summarize our results achieved with currently available diagnostic and therapeutic approaches .\na number of advances in science have been translated into real and measurable advances in patient care .\nthe emerging investigations are concentrated on different secretory proteins and their role in the development on pdr . for example\nsecreted acidic proteins rich in cystein ( sparc ) are isolated from the vitreus fluid and are increased in patients with pdr .\nfurthermore , subretinal injections of recombinant sparc adenovirus , induce pdr - like changes in the rat , thereby providing a relevant animal model for the investigation of pdr .\nrobo4 , a member of roundabout ( rabo ) family , acts as a neuronal guidance receptor and plays some role in vasculogenesis and angiogenesis .\nseveral studies have shown its effect on the formation of fibrovascular membranes in patients with pdr , and its role in choroids - retina endothelial ( rf/6a ) and human retinal pigment epithelial cells .\nsilencing the expression of robo4 in rf 6a and rpe cells inhibited their proliferation and reduced the hypoxic condition tolerance .\na number of studies have estimated increased levels of interleukin 8 in vitreous samples from patients with pdr and in patients with more severe large - vessel gliotic obliteration .\ncystein - rich 61 ( cyr61 ) induces are reported to mediate angiogenesis , and they have been shown to cause proliferation , migration , and synthetic matrix tube formation of rf/6a cells .\nrecent reports indicate that cyr61 acts as an angogenic mediator of ocular nv in vitro and in vivo . it may interact in synergy with vegf in the pathogenesis of pdr . on the other hand , rosiglitazone maleate , an oral peroxsisome - proliferating activated receptor gamma agonist and oral insulin sensitising agent with potential antiangiogenic activity , delays onset of pdr .\nthe golden standard of therapy in dm is insulin , and previous studies have emphasized its inhibitory effect on the progression of the dr .\nhowever , recent information suggests this to be controversial because insulin can stimulate vegf and hypoxia - inducible factor-1 ( hif-1 ) expression in retinal pigment epithelial cells .\nvegf is considered as a main factor for the development of the pdr , but recently , a 634c / g polymorphisms in the vegf gene was shown to be associated with pdr .\nthe expression of vegf , vegfr1 and vegfr2 levels is much higher in patients with pdr and dm , than in diabetics with pdr and dm type 2 .\nstudies that have analyzed the expression of integrins and their localization within the endothelium ( in membranes from proliferative dr isolated during the vitreoretinal surgery ) may provide new possibilities for the future treatment of the proliferative dr .\nthe results suggest an essential role of integrins alfa and beta3 in the pathogenesis of pdr .\na number of studies have shown the beneficial effect of intravitreal anti - vegf therapy .\nthe results were achieved between 13 weeks in the patients with retinal neovascularization elsewhere and neovascularization of the disc .\nassessment of the short - term safety and efficacy of inravitreally administrated bevacizumab ( an anti - vegf agent ) as an adjunctive treatment for pdr , especially in the severe cases with iris nv , has been estimated in a number of studies [ 1720 ] .\nthese studies confirmed regression of the nv , but the main disadvantage of the anti / vegf drug administration is the need of repeated injections in order to prevent recurrences of the nv .\nglucocortcoids ( e.g. , triamcinolon acetonide ) that are among the drugs used for intravitreal application can influence diabetic macular edema ( dme ) .\nthe pathogenesis of pdr is multifactorial involving both angiogenic and inflammatory processes . when administrated together with anti - vegf drugs ( bevacizumab , ranibizumab ) can induce nv and dme regression .\nthe results achieved from the studies may make this procedure an important adjunctive treatment in the management of selected cases with severe pdr .\nthe long - term results of intravitreal bevacizumab ( avastin ) , alone , in patients with pdr do not reveal any safety concerns [ 22 , 23 ] .\nfor instance , laser photocoagulation , while superior to intravitreal triamcinolone ( ivt ) or anti - vegf drugs , reduces but does not eliminate the risk of continued visual loss and is destructive to the retina .\nfocal / grid laser is more effective than ivt with fewer side effects within the initial 2 years .\nlaser or ivt are both more likely to improve the va over three years compared to the expected untreated course .\nclinical investigations include those which evaluated the efficacy of intravitreal injection of bevacizumab in preventing panretinal photocoagulation , macular thickening and visual dysfunction in eyes with severe pdr .\nthe results showed that the best corrected visual acuity increased after the combined antivegf - laser treatment while the central foveal thickness decreased .\nintravitreal injection of bevacizumab can also be used in patients with pdr , that are undergoing pars plana plana vitrectomy ( ppv ) .\nthe intravitreal administration of bevacizumab ( before ppv for pdr ) facilitates surgery and may decrease the rate of postoperative vitreous hemorrhage and improve visual acuity [ 24 , 25 ] .\nranibizumab ( lucentis ) is an affinity - matured recombinant humanized immunoglobulin monoclonal antibody fragment with a molecular weight of 48 kd that binds to and inhibits the biologic activity of all isoforms of human vegf by preventing interaction with its receptors .\nthe fragment is one third the size of a full - length antibody and readily penetrates all layers of the retina after intravitreal injection , consequently decreasing cell proliferation and vascular permeability .\nthe latest studies have also shown the positive effect of the drug , applied intravitreal in cases of dme .\nthe funding was through national eye institute that sponsored cooperative agreement that was initiated in september 2002 .\nat the moment there are eleven on - going protocols that should estimate the results of different therapeutic approaches in cases of dr .\nthe objective is to develop a collaborative network to facilitate multicenter clinical research on dr , dme and associated conditions ( fig . 2 ) . \n\n2searching for the results of different treatment modalities in cases of diabetic macular edema , according to the drcr network protocols searching for the results of different treatment modalities in cases of diabetic macular edema , according to the drcr network protocols the goals of the drcr are : \n involvement of community based practices as well as academic or university - based centres. collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the networks dedication to academic integrity and optimal clinical performance .\n involvement of community based practices as well as academic or university - based centres .\n collaborate with industry to facilitate investigations and pursue opportunities otherwise not possible and to do so in a manner consistent with the networks dedication to academic integrity and optimal clinical performance .\nthis will include the effects of cataract surgery upon dme and the effects of intravitreal plasmin to cause a posterior vitreous detachment upon dme . with the advent of new sophisticated techniques and diagnostic tools , the latest classification of the dr seems to be insufficient .\ntriggered on the molecular level , the non - responders to the standard therapy should be provided a strategy of personalized patient treatment .\nalthough individualized therapy planning seems to be expensive , we should consider the fact that the diabetic complications lead to economic and psycho - social problems .\nthe complicated treatment phase , including the sophisticated and expensive techniques of ppv , using different kind of drug substitutes do not always provide us satisfactory results .\nthe main problem at this point is not only the associated complications of the treatment , but the chronicity of the disease .\nthe long - term results of the surgery are not always stabile over time , and a lot of late complications can not be avoided .\nthus there is a need for new diagnostic and therapeutic approaches to be instituted much earlier at a time when there is no evidence of retinal damage .\nhypertension , insulin resistance , dyslipidemia and obesity , are commonly found in a combination with this stage of pdr .\nnew diagnostic images , that can discover early diabetic changes , can provide useful informations for the novel dr treatment .\npathology specific biomarkers , dna analysis in conditions of chronic diseases diagnostic and treatment , do not deliver us only information about the general concept of treatment , but also help us in the individual - treatment , individual drug response and benefits according to this strategy of individual healthcare .\nthere is a need of collaborative network , to facilitate multicenter clinical activities , and thereby development of advanced treatment algorithms for dr and dme .\nthe multidisciplinary approach to chronic diseases , such as dr can initiate research activities in different fields that could create the model of personal - based - patient - care .\nthis means , we should gain new strategies to the optimal concept that includes : \n recognize the population at risk of the diseasefollow - up before the initial changes become manifestedsearch for new approaches that can prevent the development of the diseaseearly treatmentoptimal follow - up recognize the population at risk of the disease follow - up before the initial changes become manifested search for new approaches that can prevent the development of the disease", "answer": "retinal vasculature changes in diabetic patients are most common cause of blindness among eye diseases . \n numerous studies have explored the role of the agiogenic factors in the progression of diabetic retinopathy ( dr ) . \n the balance between angiogenic and antiangiogenic factors has a determining role in the dr progression . \n current treatment modalities include laser photocoagulation , intravitreal drug application , and pars plana vitrectomy ( ppv ) . \n these maneuvers are employed with occurrence of advanced retinal changes . \n new diagnostic approaches can provide better information for the initial retinal changes thereby requiring a new dr classification and treatment guidelines . \n the results that are expected from diabetic retinopathy clinical research network ( drcr ) are at the level where prediction and prevention can not be made . \n innovative molecular - imaging technology , can pave the way for application of novel clinical approaches . \n identification of pathology - specific biomarkers and their application to diagnosis and treatment , support the individualized treatment algorithms .", "id": 528} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin 1912 , crouzon described a syndrome that consisted of brachycephaly , shallow orbits , and maxillary hypoplasia .\nsince then , craniofacial syndromes have been subcategorized into over a hundred syndromes based on the severity of the craniofacial and associated congenital malformations . \ncrouzon syndrome , along with apert , carpenter , chotzen , and pfeiffer syndromes , is one of the most common genetic disorders associated with a craniofacial syndrome .\nother facial deformities in crouzon syndrome may include prominent nose , frontal bossing , and ocular proptosis due to shallow orbits with or without hypertelorism , although age - related phenotype modifications have been reported .\npatients of crouzon syndrome may occasionally present with hydrocephalus , seizures , and mental retardation .\nthe incidence of hydrocephalus in craniosynostosis ranges from 4% to 26% [ 4 , 5 ] .\nnonetheless , short stature with growth hormone deficiency ( ghd ) and/or iron deficiency anemia ( ida ) have rarely been reported in the literature . here\nwe report a case of crouzon syndrome with hydrocephalus , also presenting with severe short stature due to ghd and ida .\nan 11 and a half - year - old boy visited our out - patient clinic for frequent dizziness and marked growth retardation .\nthe positive facial features were brachycephaly , hypoplasia maxilla , severe ocular proptosis ( hertel 's exophthalmometry measuring 22 - 23 mm on both eyes ) with hypertelorism , and low - set ears .\nhe had a 3200 gm birth weight and was born to a generally healthy mother via nsd at 40 wks ' gestational age . owing to severe hydrocephalus and cerebellar tonsil herniation ( chiari i malformation ) revealed by magnetic resonance imaging ( mri ) , he had endoscopic third ventriculostomy and\nsix months later , he received frontal advancement and ventricular shunting because of a progressive increase in ventricular size and rising intracranial pressure ( icp ) .\nhis head circumference remained at around the 50th percentile , but he had frequent respiratory tract infections during early childhood .\nthe patient had not been followed up regularly after the age of 6 years until recently .\nhe was 18.5 kg and 111.2 cm , which represented 3 standard deviation ( sd ) in body weight and 5 sd in height of his age .\nhis brother , who is 4 and a half years older , was 182 cm .\nhis parents are grossly normal and the mid - parent height is 168 cm . on admission , his general condition was stable and intelligence quotient ( iq ) around 90 .\nchromosome analysis was normal in g - banding karyotype ; however , molecular analysis identified a common mutation point of cys278phe in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene ( figure 1 ) .\nhis bone age was only 4.55 years according to the greulich and pyle atlas ( figure 2 ) , which was a 6.5 - 7- year delay .\nmri revealed obstructive hydrocephalus of both lateral ventricles with an interruption of pituitary stalk , shallow orbits , and chiari i malformation .\npituitary height was 5.6 mm in midsagittal t1-weighted spin - echo mri ( figure 3 ) , which was around mean according to tsunoda 's study . \na biochemistry profile revealed thyroid hormones and cortisol within normal limits , but blood routine showed microcytic anemia .\na growth hormone provocative test revealed a reduced peak growth hormone response of 4.57 uiu / ml in the insulin test and 2.63 uiu / ml in the clonidine test .\nthe concentrations of insulin - like growth factor 1 ( igf - i ) and insulin - like growth factor binding protein 3 ( igf - bp3 ) were also very low ( igf - i < 10.0 ng / ml , igfbp-3 : 1.5 g / ml ) . \nsevere iron deficiency anemia without thalassemia was noted ( hemoglobin : 8.8 g / dl , rbc : 4.18 million / ul , mcv : 68.2 fl ; serum iron : 7 mg / dl , ferritin : 4 ng / ml , uibc : 525 mg / dl ) with regards to the microcytic anemia . iron supplements at a dose of 100 mg / day were subscribed immediately .\nhuman growth hormone ( hgh ) subcutaneous replacement at a dose of 0.3 mg / kg / week in seven divided doses was also subscribed , and the growth velocity was 3 cm per year during the first half year .\nafter his hemoglobin and serum iron levels gradually returned to normal , his dizziness disappeared and his growth velocity increased to 5 cm per year under hgh therapy .\nwe reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with ghd , only one case report : crouzon syndrome with short stature due to partial ghd was found .\nhowever , with the progressive improvement and higher usage of imaging studies , cases of the incidence of hydrocephalus in crouzon syndrome are not uncommon . from proudman 's large study of central nervous system imaging in crouzon syndrome performed in south australia ,\nmost of those taken with follow - up computed tomographic scans were nonprogressive , even in cases of severe ventriculomegaly ( hydrocephalus ) .\n, he suggests that hydrocephalus occurs secondary to the defective formation of the cranium , so it is reasonable that in many cases the hydrocephalus is nonprogressive .\nmost ventriculomegaly in crouzon syndrome is asymptomatic and does not necessitate any treatment , unless there is a clear evidence of significantly raised intracranial pressure .\nfronto - orbital advancement and shunt system are treatments of choice . in our report case , ghd may have resulted in this patient 's growth retardation , which is not a common finding in crouzon syndrome .\nthere have been a few reports of endocrine disorders in children with shunted hydrocephalus , such as sexual precocity [ 10 , 11 ] or decreased basal levels of gh and igf-1 .\nincreased intracranial pressure has been perceived as a possible cause of pituitary dysfunction . in a series of papers by lppnen et al .\n[ 1316 ] , the growth pattern of 114 children with shunted hydrocephalus was analyzed .\nit was characterized by slow linear growth in prepuberty , accelerated physical maturation during puberty , and reduced final height .\nthis has also been shown to be associated with accelerated pubertal development in both boys and girls .\nfurthermore , they studied these patients ' serum growth hormone , plasma igf-1 , and igfbp-3 concentrations .\nthey concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients . since there was an association with growth hormone , lppnen et al . designed a study performing radiography of the sella turcica , mri of the pituitary gland , and pituitary hormone stimulation tests in a subgroup of this large series ( 54 out of 114 ) to assess pituitary size and functional capacity .\nthe results indicated that children with shunted hydrocephalus had an increased pituitary size on average .\nabout one - third of these patients had signs of reduced gh secretion and a significantly lower pituitary height , which probably contributed to their poor linear growth .\nincreased pituitary size was associated with enhanced gonadotrophin secretion , which may result in early puberty in children with shunted hydrocephalus .\nanother review article about disorders of growth and puberty in children with nontumoral hydrocephalus had similar results .\nthey concluded that central early puberty was the most frequent endocrine disorder in 21 out of 31 patients . in their cases , short stature was frequently due to meningomyelocele and rarely to gh deficiency .\nin our case , the pituitary height in mri was not smaller than normal for his age , but an interruption of the pituitary stalk was found .\nhis hydrocephalus and chiari i malformation were stationary except for the shallow orbits becoming more prominent .\nhe had severe proptosis but his visual acuity was normal . although chiari i malformation could also cause headache or dizziness , his dizziness might have been caused by severe ida , since the symptoms disappeared after anemia correction .\nthe results of hgh treatment were not satisfactory during the first half year , but became better after ida had been corrected . therefore , besides the compliance and method of hgh injection , other underlying diseases should be considered and treated if the therapeutic effect is not as expected . \ntubbs et al . reported a study which showed that a small group of children with ghd had small posterior fossa , which was similar to the features of chiari patients .\nthey hypothesized that ghd might lead to chiari i malformation through the underdevelopment of the posterior fossa . in one of their following case studies , by presenting the case of 3 brothers , 2 with ghd and chiari , and one with neither , they provided evidence of this\n. therefore , it would be interesting to see if hgh therapy leads to the improvement of chiari malformation .\nalthough surgery is not necessary in our case so far , we hope to see hgh therapy contributes to improvement of chiari malformation by the annual mri survey .\nthe diagnosis of crouzon syndrome is usually made by the patients ' clinical signs , including acrocephaly , orbital proptosis , midfacial hypoplasia with \nnose , short upper lip , high narrow palate , narrowly spaced teeth , and prognathism . to date , most patients have been shown to carry mutations of the fgfr2 gene . in chiang 's mutation analysis of crouzon syndrome in taiwanese patients ,\nthree of the 12 patients carried the cys342arg mutation , which is the most frequent mutation found in taiwanese patients .\nmolecular analysis of the fgfr2 gene can help to confirm and classify the diagnosis of craniosynostosis syndrome .", "answer": "crouzon syndrome is one of the most common craniofacial syndromes and is inherited as autosomal dominant with variable expression . \n we report an 11 and a half - year - old boy with crouzon syndrome with severe growth retardation . \n he had hydrocephalus since infancy and recently suffered from frequent dizziness . \n his bone age was only 5 years according to the greulich and pyle atlas . \n magnetic resonance imaging showed shallow orbits , obstructive hydrocephalus , and cerebellar tonsil herniation . \n growth hormone provocative tests revealed a reduced peak growth hormone response in both insulin and clonidine tests . \n severe iron deficiency anemia was noted at the same time . \n molecular analysis identified a common mutation point of cys278phe for crouzon syndrome in exon iiia of the fibroblast growth factor receptor 2 ( fgfr2 ) gene . \n since growth retardation is not a common feature of crouzon syndrome , we reviewed the literature for the incidence of hydrocephalus in crouzon syndrome and the association with growth hormone deficiency .", "id": 529} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsinonasal teratocarcinosarcoma ( sntcs ) is a very unusual and aggressive neoplasm first characterized as a separate entity by heffner and hyams in 1984.1 it is currently defined by the world health organization as a complex malignant sinonasal neoplasm combining features of teratoma and carcinosarcoma that typically includes benign and malignant epithelial , mesenchymal , and neuroepithelial elements including immature tissue with blastomatous features.2 unlike other malignant mixed germ cell tumors ( gcts ) , sntcs lacks embryonal carcinoma , yolk sac tumor , choriocarcinoma , and seminoma components .\nbased on an inadequate sample , this heterogenous tumor can be misdiagnosed as olfactory neuroblastoma , squamous cell carcinoma , undifferentiated carcinoma , adenocarcinoma , malignant salivary gland - type tumors , or adenosquamous carcinoma.2 a recent comprehensive review of the literature by wei et al revealed < 60 cases reported in the english literature.3 the primary treatment in 82% of the cases reviewed was surgery , with or without adjuvant radiation therapy ( rt ) .\nthere were high rates of recurrence and metastasis overall , although no clear prognostic factors were identified .\noverall , 1-year and 3-year survival rates were 36% and 25% , respectively , for those patients with reported outcomes.3 of all the reported cases of sntcs , only one has shown any hormone secretion : antidiuretic hormone , causing hyponatremia.4 in that case , sodium levels were a reliable marker of tumor control and were an early postoperative indicator of tumor recurrence . to date , no sntcs with elevated gct markers has been reported .\nwe present a case in which a highly radiosensitive sntcs was associated with elevated -hcg .\na 22-year - old african american woman presented to the emergency department at 16 weeks of gestation with a 2- to 3-month history of worsening headaches and a 3-week history of increasing somnolence , nausea , vomiting , weight loss , and personality changes .\na magnetic resonance imaging ( mri ) of her head revealed an 11-cm right frontal mass with a 7-cm cystic component causing significant compression of the right frontal and temporal lobes , mild herniation of the right uncus , and mild hydrocephalus .\nthe tumor extended through the anterior cranial base to the nasal cavity and paranasal sinuses ( fig .\nnoncontrast magnetic resonance imaging of the head showing a large cystic mass in the paranasal sinuses and frontal lobe . on day 2 of admission , she had rapid mental status decline and underwent an emergent decompressive craniotomy .\nthe tumor was extra - axial , and the cyst expressed a dark fluid similar to crankcase oil . the small biopsy specimen taken during this procedure revealed neoplastic cells with squamous and basaloid differentiation and necrosis , leading to the impression of basaloid squamous cell carcinoma .\nshe subsequently underwent a combined endoscopic transnasal and cranial resection of the entire anterior cranial fossa and nasal cavity mass on day 28 of admission . the surgical specimen consisted of a 9.0 8.5 3.5-cm aggregate of tan - brown soft tissue and bony fragments .\nhistologically , the tumor consisted of a heterogeneous mixture of malignant epithelial , mesenchymal , and primitive neuroepithelial elements .\ntumor infiltration of brain tissue was observed . the epithelial component included squamous and basaloid carcinoma features ( fig .\nthe mesenchymal component included areas of hypercellular smooth muscle , ranging from mildly anaplastic to overtly malignant , with focal areas of osteoid deposition ( fig .\n3 ) . the neuroepithelial component included neuroblastoma - like and primitive neuroectodermal tumor - like areas ( fig .\nimmunohistochemical staining revealed expression of vimentin , pancytokeratin , and 34e12 , with focal positivity for cd99 and synaptophysin among the heterogeneous tumor components .\n( a ) stromal smooth muscle with mitoses ( hematoxylin and eosin [ h&e ] ) . ( b ) osteoid\n( lower right ) admixed with epithelial component ( upper left ) ( h&e ) . \n\n( b ) primitive neuroectodermal tumor like area ; hematoxylin and eosin ; synaptophysin ( inset ) .\npostoperative rt was recommended after surgery but was delayed for 5 months due to a complicated hospital course and family concerns about her pregnancy .\nthe radiation planning mri showed some residual soft tissue thickening and gyral enhancement in the floor of the craniotomy site but no gross tumor .\nafter delivery of a healthy infant , she underwent a 2-month course of rt to the surgical bed to a total dose of 60 gy .\nthe follow - up mris showed no evidence of recurrent disease for 18 months post - rt .\ntwo years ( 27 months ) after finishing her postoperative rt , she was admitted for evaluation through the emergency department following an alleged sexual assault by a family member .\nher quantitative serum -human chorionic gonadotropin ( hcg ) was elevated ( 60 u / l ; normal nonpregnant range : 03 ) but did not rise as would be expected for pregnancy .\nmri of the head showed a recurrent intracranial mass in the right frontal lobe ( fig .\nshe was deemed a high surgical risk , so reirradiation of the tumor was recommended .\nradiation was delayed by 45 days , and the planning mri showed significant interval growth of the tumor with further elevation of -hcg to 130 u / l ( fig .\n( a ) magnetic resonance imaging ( mri ) showing frontal lobe recurrence 27 months after radiation therapy .\n( b ) mri showing tumor growth 45 days later , before reirradiation . ( c )\nmri showing complete response of frontal lobe mass ( and new posterior fossa disease ) 1 month after reirradiation .\nbecause of clinical concern over the origin of the serum -hcg elevation , the previous tumor tissue was examined with additional immunohistochemical staining for smooth muscle actin and -hcg expression .\nthe patient received 48 gy ( of a planned 50 gy ) of rt to the recurrent mass in 24 fractions .\nshe missed many appointments but finished most of her prescribed course in a 6-week period with no acute morbidity . computed tomography scan after the 10th fraction showed significant tumor response , and the treatment was replanned to account for the smaller tumor volume .\nher serum -hcg level dropped from a peak of 130 u / l , measured at the start of rt , to 6 u / l ( almost within normal limits ) at the end of treatment ( fig .\n7 ) , \n serum -human chorionic gonadotropin levels before and after radiation therapy ( rt ) for recurrence in frontal lobe .\none month later she was admitted to the hospital again for increasing ataxia and falls .\n5c ) but revealed at least five intracranial masses in the posterior fossa , outside of the prior rt fields . serum -hcg level was in the normal range .\nthe decision was made to palliate with 30 gy of rt to the posterior fossa in 10 fractions .\nby definition , sntcs do not contain areas of embryonal carcinoma , choriocarcinoma , yolk -sac tumor , or seminoma .\nthey are hypothesized to arise from primitive pluripotent olfactory epithelial cells rather than germ cells .\nthus they are traditionally believed to be incapable of producing gct markers including -hcg or -fetoprotein , although they have rarely been noted to produce pituitary hormones.4 these tumors comprise varying combinations of epithelial , mesenchymal , and neuroectodermal components exhibiting varying maturation\n. the mesenchymal component may appear along a continuum from benign to malignant and can include mature components such as cartilage , bone , and striated or smooth muscle .\nmalignant sarcomatous transformation is also documented.1 \n 5 \n 6 \n 7 \n in this case , smooth muscle actin highlighted an anaplastic smooth muscle component in this heterogeneous tumor .\nthere are rare reports of pure leiomyosarcomas secreting -hcg in the literature.8 \n 9 \n 10 in the absence of the gct components just mentioned , the neoplastic smooth muscle component of the tumor with expression of -hcg was the likely source for the elevated serum -hcg levels . because this patient was pregnant on initial presentation , any tumor - related -hcg production at that time\nhowever , on recurrence , tumor production of -hcg was confirmed with elevation of serum -hcg , expression of -hcg on the smooth muscle component of the tumor tissue , and correlation of serum -hcg levels with changes in tumor size seen on imaging .\nthis patient 's recurrent tumor initially showed a complete response to rt by both serum marker and imaging criteria .\nsubsequent tumor growth outside of the rt field was not associated with elevation of serum -hcg .\nsntcs is a rare and unusual neoplasm that lacks embryonal carcinoma , yolk sac tumor , choriocarcinoma , and seminoma components .\nthe source of -hcg production was traced to a neoplastic smooth muscle component of the tumor .\nserum levels of this hormone were a reliable tumor marker during the patient 's first recurrence and subsequent rt .", "answer": "background and importance sinonasal teratocarcinosarcoma ( sntcs ) is an unusual and aggressive neoplasm characterized by the combination of teratoma and carcinosarcoma features that is often misdiagnosed based on a biopsy sample . \n approximately 60 cases have been reported in the english literature , but none have been associated with serum tumor markers . \n we report a case of sntcs with elevation of serum -human chorionic gonadotropin ( hcg ) level . \n \n clinical presentation the patient was a 22-year - old pregnant woman at diagnosis , and her -hcg level was appropriately elevated . \n her initial treatment was a surgical resection followed by radiation therapy ( rt ) . \n two years later , the patient had a pregnancy work - up after a sexual assault . her serum -hcg was elevated , but a nongravid uterus was seen on ultrasound . magnetic resonance imaging ( mri ) of the head revealed an intracranial tumor recurrence in the right frontal lobe . during salvage rt , -hcg decreased rapidly to normal levels , with a complete tumor response on mri . \n retrospective examination of the initial surgical specimen showed expression of -hcg associated with the anaplastic mesenchymal component . \n \n conclusion this is the first reported case of a -hcg secreting sntcs . the source of -hcg production was traced to a neoplastic smooth muscle component of the tumor .", "id": 530} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe treatment options for graves ' disease consist of antithyroid drugs , radioactive iodine ( rai ) therapy , and surgery .\nrai therapy has been used for the treatment of graves ' disease for more than seven decades , and in most studies , it has not been associated with an increased risk of cancer . on the other hand ,\nseveral studies have proposed the potential increase in thyroid malignancies with rai treatment [ 2 - 4 ] . here , we describe a very rare case of anaplastic thyroid carcinoma ( atc ) associated with graves ' disease , following rai treatment .\na 42-year - old woman was referred to our clinic in 1998 , because of palpitations , hand tremor , and laboratory findings of hyperthyroidism ( serum thyrotropin [ thyroid - stimulating hormone , tsh ] 0.05 iu / ml [ reference range , 0.17 to 4.05 ] , free thyroxine 4.01 ng / dl [ reference range , 0.79 to 1.86 ] , and positive tsh receptor antibody at 201.7% [ percent binding inhibition index , radioreceptor assay , reference range ; 15.0% ] ) , and had been diagnosed as graves ' disease .\na technetium-99 m thyroid scan showed enlarged and homogeneously increased uptake , and ultrasonography revealed a diffuse goiter without nodules .\nthe patient received 200 mg / day of propylthiouracil and -adrenergic blocking agents for 1 year .\nhowever , due to recurrent hyperthyroidism , she received rai therapy twice with an administered dose 370 mbq ( 10 mci ) , 296 mbq ( 8 mci ) , each .\ntwo years later , she received thyroid hormone replacement due to subsequent hypothyroidism at a local clinic . in september 2010 , over 10 years later , she revisited us with complaints of hoarseness , dysphagia , and dyspnea , which had been presented for 2 months .\nan anterior neck mass , which was hard and fixed , and some lymph nodes ( lns ) around the mass were palpable .\nher chest radiography showed a tracheal narrowing and deviation to the right without active lung lesion . on computed tomography ( ct ) of the neck ,\npositron emission tomography - ct , an intense hypermetabolic lesion was noted in the thyroid gland and lns on her left neck without distant metastasis .\na total thyroidectomy with selective neck dissection , tracheal sleeve resection , and end - to - end anastomosis were performed .\nsubsequently , she had concurrent cisplatin - based chemoradiotherapy for her neck and superior mediastinum ( total 6,600 cgy/33 fractions ) .\nafter 4 months of follow - up , despite the aggressive treatment , the disease progressed .\non neck ct , a new focal necrotic mass on the left side of her neck was noted , suggesting local recurrence .\nthe mass extended up to the tracheal lumen and the patient died of sudden uncontrolled bleeding in the airway .\nthe patient in this case received rai therapy twice for recurrent hyperthyroidism . after more than 10 years , she developed respiratory symptoms and was finally diagnosed with atc .\nthis case raises questions about the causal relationship between rai therapy for graves ' disease and the subsequent occurrence of thyroid cancer .\nalthough it has been widely accepted that rai is safe , some studies have suggested that rai therapy is possibly associated with a small increased risk of thyroid cancer [ 2 - 4 ] .\ndegroot reported that the rai treatment can induce an increase of thyroid antibodies , such as tsh receptor antibody , and it was suggested that thyroid stimulating antibodies play an important role in thyroid carcinogenesis .\nthese antibodies also can stimulate angiogenesis , which contributes to thyroid tumor cell growth , by activating vascular endothelial growth factor .\nsturgis reported cytomorphologic alterations in thyroid follicular epithelium , which is associated with rai therapy . before treatment , graves ' disease typically lack significant atypia , while after rai therapy , nuclear atypia , and progressive cellular metaplasia could be seen microscopically .\nfurthermore , it was prominent in those who remain in a hyperthyroid state despite rai treatment .\nin addition to our case , two previously reported cases of atc after rai therapy for documented graves ' disease are summarized in table 1 .\nbaker reported a 64-year - old woman with atc 12 years after rai therapy . because thyroid toxicity persisted after one course of rai therapy , the patient received a second therapy in 4 months .\ngossage et al . reported a 46-year - old woman who had her first rai therapy , when aged only 23 years .\nalthough she underwent partial thyroidectomy prior to the rai therapy , hyperthyroidism recurred and she received several subsequent doses of radioiodine .\nan analysis of these cases is noteworthy , because since the interval to cancer diagnosis was over 10 years in all cases , it supports the importance of long - term vigilance in patients receiving rai therapy .\nin addition , these cases had something in common in terms of the occurrence of atc after repetitive , small doses of rai therapy .\nthe cooperative thyrotoxicosis therapy follow - up study showed that thyroid neoplasms developed in children treated with lower , rather than higher , doses of rai therapy , which is compatible with our finding .\ntherefore , it can be hypothesized that multiple courses of rai therapy , with small doses , may play a role in carcinogenesis , especially in the poorly differentiated type .\n. demonstrated that i treatment inactivates the tumor suppressor gene that is frequently found in atc rather than in the differentiated type .\nhowever , to discuss the causal relationship between rai therapy and the occurrence of cancer , the number of reports is too small , therefore a population - based study is required and this is a limitation of our report .\nin addition to the rai therapy , we can not exclude that graves ' disease itself might also increase the risk of cancer . although our patient had no thyroid nodule by ultrasonography ,\nthe palpable thyroid nodules found in graves ' patients have a 16.9% malignancy rate , which is higher than that of the general population .\nmoreover , the finding that thyroid autoantibody stimulates the malignant transformation of the thyroid gland supports this suggestion .\nit is not clear that the occurrence of atc reported here was influenced by rai therapy or , alternatively , it may only represent the delayed recognition of a rare change in the natural history of graves ' disease .\nnevertheless , this report is worthwhile since it presents a very rare case of atc that occurred 11 years after rai therapy for graves ' disease .", "answer": "radioactive iodine ( rai ) therapy has been used as a treatment option for graves ' disease , and it has been widely accepted to be safe . on the other hand , some evidence suggests that rai therapy is possibly associated with a small increased risk of thyroid cancer . \n herein , we report a rare case of anaplastic thyroid carcinoma ( atc ) associated with graves ' disease , following rai treatment . a 42-year - old woman had been diagnosed with graves ' disease and although she was treated with an antithyroid drug , she remained in a hyperthyroid state , which led to two rai treatments . \n more than 10 years later , the patient revisited our clinic due to hoarseness , dysphagia , and dyspnea , which had lasted for 2 months . \n neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma . \n the patient underwent total thyroidectomy and was finally diagnosed as having an atc . \n it is not clear if the occurrence of atc reported here was influenced by the rai therapy or alternatively , it may only represent the delayed recognition of a rare change in the natural history of graves ' disease . \n nevertheless , this report is worthwhile since it presents a very rare case of atc that occurred eleven years after the rai therapy for graves ' disease .", "id": 531} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlemierre 's syndrome is a septic thrombophlebitis of the internal jugular vein ( ijv ) commonly caused by anaerobic oropharyngeal flora that is usually followed by fulminant sepsis and rapid death in the pre - antibiotic era . since the introduction of antibiotics , the morbidity and mortality associated with this syndrome have been dramatically decreased .\nhowever , delay in diagnosis and antibiotic treatment resulting in poor clinical outcome is not uncommon as physicians are less familiar with this infection and initial manifestations are often non - specific .\nwe describe a case of a patient with lemierre 's syndrome whose the diagnosis was not suspected until blood culture grew fusobacteirum necrophorum .\nan otherwise healthy 36-year - old male presented to our institute with a 4-day history of low - grade fever accompanied by sore throat , myalgia and nausea .\nphysical examination was remarkable for a temperature of 38.1c and an injected pharynx without any neck tenderness or swelling .\ncomplete blood cell count showed thrombocytopenia with platelet of 45,000/ul , hemoglobin of 14.8 g / dl and cell count of 8700 cells / ul ( neutrophil of 85% and band form of 6% ) .\nhe was diagnosed with viral upper respiratory tract infection and was admitted to general medicine service for rehydration .\nhe received 2 l of intravenous normal saline over night ; however , on the 2 day of hospitalization , he developed high fever of 39.2c along with pleuritic chest pain and low blood pressure of 80/50 mmhg .\nblood cultures were obtained and empirical antibiotics ( vancomycin and piperacillin / tazobactam ) were initiated .\nchest x - ray revealed bilateral patchy and irregular parenchymal opacities and subsequent chest computed tomography demonstrated right - sided pleural effusion and multiple thick - walled cavitary and nodular opacities consistent with septic emboli [ figure 1 ] .\nhis blood cultures grew f. necrophorum on the following day and his antibiotic therapy was narrowed down to piperacillin / tazobactam .\nhis blood pressure was normalized without using any vasopressor or mechanical ventilation ( he received 5 l of intravenous normal saline in total ) .\nvenous duplex ultrasonography was immediately obtained after the blood culture and demonstrated thrombus in the left ijv .\npatient was finally diagnosed with lemierre 's syndrome and remained stable through rest of the hospital course .\npiperacillin / tazobactam was continued for 7 days and he was discharged home with a 4-week course of intravenous ertapenem and recovered well from the infection .\n( b - d ) chest computed tomography showed multiple thick - walled cavitary and solid nodules ( arrows ) and right - sided pleural effusion ( arrow heads )\nlemierre 's syndrome or postanginal sepsis is a rare , but potentially fatal infection of the ijv .\nit is usually caused by f. necrophorum although a wide variety of bacteria , including bacteroides , eikenella , porphyromonas , prevotella , proteus , streptococcus , peptostreptococcus and staphylococcus aureus has been reported as causative organisms .\nthe infection typically starts in the palatine tonsils or peritonsillar tissue and spread into the ijv - containing lateral pharyngeal space though causing septic thrombophlebitis though infection originated from pharynx , middle ear , sinus and parotid gland has also been described .\nthis septic thrombophlebitis is usually followed by distal septic embolization , resulting in multi - organ involvement with lung being the most commonly affected site with reported incidence of 97% .\nother commonly involved sites are joints , muscle , soft - tissue , meninges , spleen and liver .\nwhy f. necrophorum , a normal inhabitant of human oropharynx , becomes invasive is unclear .\nloss of pharyngeal mucosal integrity caused by bacterial or viral infection might play a major role as several cases of lemierre 's syndrome proceeded by acute mononucleosis have been reported .\nthe increased production of leucotoxin is also pivotal for the pathogenesis as it can avidly activate platelet resulting thrombus formation in the ijv .\nlemierre 's syndrome is classically described as a constellation of symptoms of fever , sore throat , neck swelling , pulmonary involvement and arthralgia that frequently affects young healthy adults .\nnevertheless , initial clinical presentation can be subtle and sometimes persistent fever is the only prominent symptom and the syndrome is frequently not suspected until the microbiologic data is available hence high - level of clinical suspicion is needed for the timely diagnosis .\nphysical examination might reveal an exudative tonsillitis or milder form of pharyngitis ; however , these oropharyngeal signs might not be evident as the septic thrombophlebitis or metastatic complication usually occurs 1 - 3 weeks after the primary infection .\ntypical signs of ijv thrombophlebitis are pain and swelling along the sternocleidomastoid muscle , but they are found in only approximately a half of patients .\ndiagnosis of lemierre 's syndrome is established on the presence of thrombus in ijv and positive blood culture .\ncomputed tomography of neck with contrast is the diagnostic modality of choice to demonstrate the thrombus .\ndoppler ultrasonography is an alternative since it is less invasive and can be done at bedside though it is less sensitive particularly in the area deep to clavicle and mandible and can miss newly formed thrombus with low echogenicity .\nprolonged course of intravenous antibiotic ( 3 - 6 weeks ) covering f. necrophorum and oral streptococci is the cornerstone of treatment . as beta - lactamase producing strain of f. necrophorum\nappropriate first - line antibiotics should be one of the following : beta - lactam / beta - lactamase inhibitor , carbapenem , ceftriaxone + metronidazole and clindamycin .\nthe role of anticoagulation is unclear , but is generally not indicated unless there is evidence of expansion of the thrombus .\nsurgical ligation or excision of the ijv might be necessary in the case of uncontrolled sepsis or septic emboli despite adequate antibiotic .\nwe report a case of healthy young male who presented with flu - like symptoms and was initially mistaken for viral upper respiratory tract infection .\nintensivists should have a high index of suspicion for this diagnosis in otherwise healthy young adult .\nhistory of preceding pharyngitis or evidence of septic emboli , especially to the lung may provide an additional clue to the diagnosis .", "answer": "lemierre 's syndrome is an uncommon , but fatal infection of the internal jugular vein ( ijv ) that is usually caused by fusobacteirum necrophorum although a wide range of bacteria has been reported as causative agents . \n typical symptoms include fever , sore throat , neck swelling , pulmonary symptoms and arthralgia ; however , the diagnosis of this infection is frequently overlooked as initial manifestation might be subtle and non - specific . \n definite diagnosis requires positive blood culture and radiological evidence of thrombus in the ijv . \n we describe a case of a patient with lemierre 's syndrome who was initially misdiagnosed with viral upper respiratory tract infection . \n high index of suspicion is pivotal to the diagnosis of this infection and lemierre 's syndrome should always be considered as a potential cause of sepsis in an otherwise healthy patient .", "id": 532} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 68-year - old male presented complaining of sudden and profound loss of central vision in his left eye following blunt eye trauma .\nhe reported seeing a large , dense , central scotoma that began fading 1 h after the injury .\nhe was emmetropic , phakic , and had no significant ophthalmic history . on examination , 24-h postinjury , best - corrected visual acuity ( bcva ) in the left eye\noct of the left macula ( spectralis , heidelberg engineering , 5-line raster acquisition protocol ) revealed abnormal hyper - reflectivity and nodularity of the photoreceptor os layer .\ninterestingly , the patient was found to have prominent abnormalities on infrared imaging using the infrared reflectance protocol of the spectralis oct [ fig . 1 ] .\ninfrared imaging of the left fundus revealed diffuse infrared hypo - reflectance dotted with spots of very low pixel value ( dark ) , creating a stippled appearance .\npoint - to - point correlation between the infrared and oct images using the spectralis software ( heidelberg engineering , germany ) demonstrated that the infrared dark spots correlated with foci of thickened os seen on 5-line raster oct .\nno pathology of the superficial retina , retinal pigment epithelium or choroid was detected using red - free reflectance , fundus auto - fluorescence , and enhanced - depth imaging ( edi ) , respectively .\n30 posttrauma , and at 8 months posttrauma , bcva in the left eye was 20/25 and the retina appeared normal on examination and when imaged with infrared reflectance , 5-line raster oct , fundus auto - fluorescence , and edi [ fig .\n2 ] . left fundus images at day 1 postblunt trauma to the left eye .\n( b ) infrared confocal scanning laser ophthalmoscope fundus image demonstrating stippled hypo - reflectance at the macula . ( c )\noptical coherence tomography of the macula demonstrating abnormal hyper - reflectivity of the outer segments ( between arrowheads ) .\n( b ) infrared confocal scanning laser ophthalmoscope fundus image reveals resolution of the infrared hypo - reflectance\nin this case , there is a clear temporal relationship between eye trauma , transient vision loss , transient oct changes consistent with cr , and transient infrared hypo - reflectance .\ncases of cr detectable on oct , but not fundus examination have been described , confirming that some cases of cr are subclinical . to the best of the authors knowledge\nthe pathology of cr has been studied histologically and on oct , and comprises fragmentation of the photoreceptor os without injury to the inner retina .\nas demonstrated by our case , this manifests on 5-line raster oct as abnormal hyper - reflectivity of the os layer .\nthis oct feature is subtle and is easily overlooked if the study is not carefully scrutinized .\nour case implicates infrared imaging as a diagnostic adjunct for detecting subclinical cr . since focal dark spots on infrared imaging correlated with points of nodular os thickening in our case\n, we infer that the infrared hypo - reflectance in cr is caused by increased absorption of infrared light by an abnormal os layer . with a wavelength of 820 nm ,\nthe infrared mode of the spectralis oct penetrates deeper into the retina than modalities using visible wavelengths of light .\nit is , therefore , useful for detecting outer retinal pathology , such as that of cr .\nthe spectralis uses a confocal scanning laser ophthalmoscope ( cslo ) and records infrared reflectance without barrier filters . compared with conventional recording techniques\n, cslo improves image resolution by using a higher emission of light energy and by reducing the capture of scattered light .\nfurther studies are required to determine whether infrared hypo - reflectance is a consistent feature in all cases of cr , and whether this imaging modality has greater sensitivity for detecting subclinical cr than 5-line raster oct .\nnevertheless , this case suggests that infrared imaging may have a role as a diagnostic adjunct for detecting subclinical cr .\nwe recommend that clinicians consider performing infrared imaging of the retina when managing a patient who presents with unexplained vision loss after blunt trauma and a normal - appearing fundus .", "answer": "commotio retinae ( cr ) is an outer retinal disorder following blunt trauma to the eye . \n histologically it is characterized by disruption of the photoreceptor outer segments ( os ) , typically without injury to other retinal layers . \n using spectral - domain optical coherence tomography ( oct ) the condition is visible as hyper - reflectivity of the os . \n most cases of cr are associated with transient grey - white discoloration of the retina and are easily diagnosed clinically , but there have been reports of oct - confirmed cr without retinal discoloration . \n it is likely that this subclinical variant of cr is under - recognized as the oct features of cr are subtle . \n here , we report a case of oct - confirmed subclinical cr that demonstrated prominent infrared hypo - reflectance , using the infrared protocol of the spectralis oct , heidelberg engineering . \n this case suggests that infrared reflectance may have a role in diagnosing cases of subclinical cr .", "id": 533} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe calcifying odontogenic cyst ( coc ) was first described by gorlin and his colleagues ( 1962 ) , as a separate entity of odontogenic origin .\nas all lesions are not cystic and the biological behavior is often not compatible with a cyst , there is a controversy as to whether coc is a cyst or a tumor .\nbased on the dualistic concept , some authors consider that coc contains two entities : a cyst and a neoplasm .\nhowever , others regard coc as a tumor with a tendency for cyst formation . based on this monistic concept the world health organization ( who ) has classified all cocs as neoplasms .\nthe cystic lesions are termed as calcifying cystic odontogenic tumors ( ccot ) and the neoplastic entity as a dentinogenic ghost cell tumor(dgct ) .\nmicroscopically , it consists of ameloblastomatous epithelial islands , with areas of ghost cell formation and varying amount of dentinoid material . the purpose of this article is to report a case of dentinogenic ghost cell tumor in a 21-year - male , in the posterior region of the mandible , which is at a comparatively younger age and at an infrequent site .\na 21-year - old male patient reported to the department of oral pathology and microbiology , government dental college and hospital , aurangabad , with the complaint of swelling in the left posterior region of the lower jaw , of one - month duration .\nextraorally a diffuse swelling was seen over the left mandibular angle region [ figure 1 ] .\ndiffuse swelling over mandibular angle region on left side intraoral examination revealed the presence of a bony hard swelling , extending from 37 to the retromolar region [ figure 2 ] .\nthe color of the lesional area was the same as that of the adjacent mucosa .\nit showed a smooth surface all over , except a small growth distal to 37 , which subsided after antibiotic treatment .\nbony hard swelling extending from 37 to retro - molar region with a small 1 1 cm reddish growth , distal to 37 radiographs revealed a well - defined lesion extending from 34 to the ramus of the mandible with scalloped borders .\nan occlusal radiograph showed buccal cortical expansion in the retromolar region on the left side [ figure 4 ] .\nroot resorption of 36 and 37 buccal cortical expansion in the left retro - molar region histopathological examination revealed a tumor mass composed of islands of odontogenic epithelial cells with hyperchromatic nuclei in a mature connective tissue stroma .\nameloblastoma - like islands with peripheral columnar , polarized basal cells , and central stellate reticulum - like cells were also noted .\nnumerous ghost cells with faint eosinophillic cytoplasm and a shadow of nuclear outlines were noted within the epithelial islands as well as in the connective tissue [ figure 5 ] .\nmany foreign body - type multinucleated giant cells were observed surrounding the ghost cells in the connective tissue stroma [ figure 6 ] . some ghost cells exhibited calcification .\nmasses of dentinoid - like material were present in close proximity to the epithelial islands ; in which some showed calcification [ figure 7 ] .\nameloblastomatous epithelial island with ghost cells and dentinoid material ( h and e , 40 ) giant cells surrounding ghost cells in the connective tissue stroma ( h and e , 100 ) calcifying ghost cells and dysplastic dentin ( h and e , 100 ) tumor cells infiltrating adjacent bone ( h and e , 400 )\ncalcifying odontogenic cyst constitutes 1 to 2% of all odontogenic tumors in which 88.5% are cystic and the remaining 11.5% are solid tumors .\n( 1981 ) , termed these solid tumors as dentinogenic ghost cell tumors as they are made up of an ameloblastomatous epithelium with areas of ghost cell formation and varying amounts of dentinoid .\nfejerskov and krogh ( 1972 ) , interpreted it as a tumor or hamartoma with a marked tendency for cystic degeneration .\nthey stated that there is no reason to assume that epithelial change can develop only in the pre - existing cyst wall , but rather cystic degeneration can take place in the of the proliferating epithelial island .\nthese authors also noted that the lesion is not invariably cystic and suggested the term calcifying ghost cell odontogenic tumor .\nas it appeared to be one variety of ameloblastoma and could recur after conservative surgical treatment , shear ( 1983 ) , preferred the term dentinoameloblastoma .\nellis and shmookler ( 1986 ) , preferred the term epithelial odontogenic ghost cell tumor as epithelial cells appearing like ghost cells were the most distinctive feature of this neoplasm .\n( 1990 ) , suggested the term odontogenic ghost cell tumor for the same neoplastic form of coc .\nthe average age for the presentation of this lesion is 50 years , ( range 17 72 years ) with slight male predilection .\ntumor occurs in the maxilla and the mandible with equal frequency , with canine to first molar region the most often the affected site .\npatients are usually without symptoms , although with a few complain of pain or discomfort .\nthe present lesion was seen in a 21-year - old male , in the posterior region of the mandible on the left side , at a comparatively younger age , and contrary to the common anterior region of the jaw .\nroot resorption or an impacted tooth in relation to the tumor mass is also noted in some cases .\nmicroscopic features show islands of odontogenic epithelial cells with hyperchromatic nuclei in a mature connective tissue .\nloosely arranged stellate reticulum - like cells may be seen enclosed by the odontogenic epithelium .\nthe epithelium may show ameloblastomatous proliferation with a well - defined basal layer of columnar or cuboidal cells and hyperchromatic nuclei , which are polarized away from the basement membrane . on account of the multipotentiality of odontogenic epithelium , the histological presence of areas similar to different odontogenic tumors , such as , ameloblastoma\n, odonto - ameloblastoma , ameloblastic fibro - odontoma , odontoma , adenomatoid odontogenic tumor , and cementoma may be seen .\ntwo characteristic features of dgct distinguish it from ameloblastoma and other odontogenic tumors , numerous ghost cells , and masses of dentinoid material .\nghost cells are characterized by the loss of nuclei , preservation of basic cellular outlines , and resistance to degradation .\nalthough cellular outlines are usually well defined , they may be blurred , and as a result the groups of ghost cells appear fused .\ndystrophic calcification may occur in some of the ghost cells , initially seen as fine basophilic granules and later as small spherical bodies .\nsometimes ghost cells break through the basement membrane and come in contact with the connective tissue , where they evoke a foreign body reaction with the formation of multinucleated giant cells .\nmost authors interpreted the changes in the ghost cells as aberrant or incomplete keratinizations or even as true keratinizations .\nabram and howell ( 1968 ) , presented the concept that the keratin appeared to originate from the degeneration of squamous cells .\nlevy ( 1973 ) , investigated the ghost cells in odontomas and suggested that they represented squamous metaplasia with subsequent calcification caused by ischemia .\nsedano and pindborg ( 1975 ) , thought that ghost cells represented different stages of normal and aberrant keratin formation and that they were derived from the metaplastic transformation of odontogenic epithelium .\nother investigators were of the opinion that ghost cells might be the product of abortive enamel matrix in the odontogenic epithelium , however , the morphology of ghost cells seems to be different from that of the enamel matrix .\nanother characteristic feature is the formation of dentinoid or osteoid material , which represents an inflammatory response of the body to the presence of ghost cells .\nabrams and howell ( 1968 ) , stated that masses of ghost cells induce granulation tissue to lay down the juxtaepithelial osteoid , which may calcify .\nsauk ( 1972 ) , sapp and gardner ( 1977 ) , and nagao et al .\n( 1982 ) , stated that the juxtaepithelial osteoid or dentinoid are frequently found in areas free of either granulation tissue or ghost cells and postulated that it might be an inductive phenomenon rather than an inflammatory response .\nto date , it is not clear whether this material represents a true inductive effect or merely a metaplastic change in the connective tissue .\nsimilar histopathological features are seen in the present case , and hence it has been diagnosed as \ndentinogenic ghost cell tumor . in the immunohistochemical evaluation of a case of dgct, by piatelli a et al .\nthe epithelial cells were positive for cytokeratins , characterizing the presence of an odontogenic epithelium , while the calcified bodies and ghost cells were devoid of any immunoreactivity , representing that they were derived from the metaplastic transformation of the odontogenic epithelium or were a product of the coagulative necrosis of the odontogenic epithelium .\nthere was also a strong positivity of the odontogenic epithelium for bcl-2 and mib-1 , whereas , only a rare positivity for p-53 .\nthe ghost cells , giant cells , and dentinoid material were completely negative . it was concluded that the cells that expressed bcl-2 and mib-1 probably represented the portion of the tumor that proliferated and that could undergo malignant transformation . initially enucleation was the primary treatment for central dgct , but local recurrence was noted .\nthe patient has been under observation since nine months and no recurrence has been noted till now .\ncoc has been seen to be of extensive diversity in its clinical and histopathological features as well as in its biological behavior .\nthe present case of 21-year - old male was diagnosed as dgct , a tumorous form of coc , due to its characteristic histological features ; numerous ghost cells and dentinoid material .", "answer": "dentinogenic ghost cell tumor ( dgct ) is a rare tumorous form of calcifying odontogenic cyst and only a small number of cases have been described . \n it is a locally invasive neoplasm that is characterized by ameloblastoma - like epithelial islands , ghost cells and dentinoid . \n the present report describes a case of a 21-year - old male with a tumor in the posterior region of the mandible , showing features of dgct .", "id": 534} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto foster greater coordination on surveillance , research , education , and prevention of tickborne diseases , cdc established ticknet during 2007 .\nticknet is a public health network that includes partners from state health departments and academic institutions collaborating through the emerging infections program ( eip ) , staff of state and local health departments collaborating through the epidemiology and laboratory capacity ( elc ) cooperative agreement , and cdc staff in the division of vector - borne diseases and the division of parasitic diseases and malaria .\nticknet provides funding to state and local health departments through the elc cooperative agreement to help sustain and enhance routine surveillance for tickborne diseases .\napproximately 18 state and local health departments are funded annually for lyme disease surveillance , with priority given to states with a reported incidence of lyme disease greater than the national average and to bordering states where the disease may be spreading . during 2014 , an additional 7 state and local health departments received elc funding to support surveillance for other tickborne diseases . together with elc funding for program support , funding through eip has allowed ticknet partners in maryland , minnesota , and new york to undertake special studies to quantify underreported tickborne diseases .\nthese studies include a review of patient charts and codes from the international classification of diseases , ninth edition , and provide insights into the use of electronic medical records for public health surveillance .\nother studies in massachusetts , minnesota , and new york are examining ways to streamline the evaluation of positive laboratory reports by using random sampling methods .\n, ticknet partners at eip sites in connecticut , maryland , minnesota , and new york conducted a survey of commercial , clinical , and state laboratories to evaluate practices and volume of testing for 5 leading tickborne diseases . collectively , 7 large commercial laboratories reported testing 2.4 million patient specimens for evidence of b. burgdorferi infection during 2008 , at an estimated cost of $ 492 million . after correcting for test sensitivity , specificity , and stage of illness ,\nthe overall frequency of infection among patients for whom samples were tested was estimated at 12% .\napplied to the total number of specimens , this percentage yielded an estimated 288,000 true b. burgdorferi infections ( range 240,000444,000 ) among source patients during 2008 ( 18 ) .\nresults of this study will be compared with results of other ongoing cdc studies to estimate the overall frequency of lyme disease and other tickborne infections in the united states .\nto better quantify the public health burden of tickborne diseases , ticknet eip partners in connecticut , maryland , minnesota , and new york have undertaken a study to quantify current costs associated with individual cases of lyme disease . begun during 2014 ,\nthe cost of lyme disease study uses a prospective survey design to capture individual and societal costs of lyme disease , including out - of - pocket medical costs , nonmedical costs , and productivity losses , as well as total direct medical costs to society by using billing codes from enrolled patients providers .\nthis estimate will be used to guide impact assessments of current and future prevention methods . as an adjunct to personal protective measures such as use of insect repellents ,\nseveral yard - based interventions have been proposed to reduce tick abundance in the home environment . to assess the efficacy of such interventions in preventing human illness , ticknet sites have instituted a series of studies to evaluate the efficacy of novel and commercially available prevention strategies .\none study , a randomized , blinded , placebo - controlled , multistate trial assessing the effectiveness of acaricide barrier sprays , will cover 2,700 households in 3 states , with outcomes measures including tick density on acaricide - treated properties , the number of tick human encounters , and the number of tickborne diseases in humans .\na second study , begun in connecticut during 2012 , uses a similar design to evaluate the effectiveness of bait boxes that apply fipronil to rodents that are the reservoirs of b. burgdorferi\n. used by veterinarians to prevent flea and tick infestations on dogs , fipronil kills ticks on the rodents for several weeks and may potentially interrupt the local transmission cycle of b. burgdorferi .\nrecent experience indicates that additional tickborne pathogens are waiting to be discovered . in collaboration with the tennessee and minnesota health departments , the mayo clinic , and vanderbilt university ,\nticknet has recently initiated a study to identify novel agents of tickborne disease . over the next 3 years ,\n> 30,000 clinical specimens from us patients with suspected tickborne diseases will be screened by using high - throughput molecular methods designed to detect bacteria , followed by use of genomic sequencing to characterize detected pathogens .\nthe ultimate goal is to better describe the epidemiologic and laboratory features associated with recognized and novel tickborne pathogens and to guide the development of new diagnostic methods .\nalthough sometimes overlooked , tickborne diseases pose an increasing threat to public health . factors driving the emergence of tickborne diseases are poorly defined , but current prevention methods are clearly inadequate . addressing this problem\nrequires a multidisciplinary approach with input of entomologists , epidemiologists , educators , and infectious disease and communications specialists .\nbuilt on the pillars of the eip and the elc cooperative agreements , ticknet provides a collaborative network that brings together these resources at the federal and state levels to enhance surveillance , improve prevention , and identify new tickborne diseases .", "answer": "ticknet , a public health network , was created in 2007 to foster greater collaboration between state health departments , academic centers , and the centers for disease control and prevention on surveillance and prevention of tickborne diseases . \n research activities are conducted through the emerging infections program and include laboratory surveys , high - quality prevention trials , and pathogen discovery .", "id": 535} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninfections are common in patients with cirrhosis and have been found in up to 66% of patients with variceal hemorrhage .\nprophylactic treatment with third generation cephalosporins is recommended in patients with advanced cirrhosis and gastrointestinal bleeding to cover for the predominant causative gut flora organisms , .\ntreatment is recommended even if no causative organism is identified as up to 50% of patients with cirrhosis and clinical sepsis have negative cultures . identifying appropriate antimicrobials\ncan be challenging without a causative organism , and the empiric use of broad spectrum antimicrobials contributes to multidrug resistant organisms .\nwe report the first known case of paracoccus yeeii bacteremia in a patient with decompensated cirrhosis who presented with variceal hemorrhage . this rare gram negative organism may not be susceptible to third generation cephalosporins .\nthis finding may have implications for the management of infected but culture negative patients with cirrhosis .\na 42 year old gentleman with decompensated cirrhosis from genotype 1a ( g1a ) hepatitis c ( hcv ) had been treated with 24 weeks of ledipasvir and sofosbuvir which ended 4.5 months earlier .\nthe patient presented with new onset jaundice ( total bilirubin 23 mg / dl , direct bilirubin 18 mg / dl , alkaline phosphatase 99 u / l , alanine aminotransferase 31 u / l , aspartate aminotransferase 86 u / l ) that peaked to total bilirubin 44 mg / dl and direct bilirubin 31 mg / dl . model for end - stage liver disease ( meld )\nscore on admission was 27 . given the report of subjective fevers in the setting of recently treated k. pneumoniae bacteremia of unknown source , admission blood and urine cultures were obtained but were without growth .\nmolecular studies revealed hcv relapse ( hcv viral load = 4.44 log iu / ml ) without ns5b resistance ( insufficient sample for ns5a ) and undetectable hepatitis b ( hbv ) and adenovirus .\nthere was no serologic evidence of acute infection with hepatitis e , cytomegalovirus ( cmv ) , or epstein barr virus ( ebv ) .\nliver biopsy demonstrated cirrhosis with moderate chronic inflammation , focal severe neutrophilic infiltrates with cholestasis , and ductular proliferation .\nmagnetic resonance imaging ( mri ) and magnetic resonance cholangiopancreatography ( mrcp ) showed no cholangitis or abscess . although drug induced liver injury from ciprofloxacin was clinically suspected , two sets of blood cultures were obtained daily due to concern for infection and lack of clinical improvement . the patient elected discharge but was readmitted within 24 hours with hematemesis from variceal hemorrhage and portal hypertensive gastropathy .\nempiric treatment for undifferentiated septic shock including spontaneous bacterial peritonitis prophylaxis were ceftriaxone 2 g iv every 24 hours , metronidazole 500 mg iv every 8 hours , and vancomycin 2 g iv every 12 hours .\ndiagnostic paracentesis was again attempted but the patient had minimal ascites . given the lack of clinical improvement and the finding of bowel edema and severe colitis on computer tomography , infectious disease was consulted .\nit was recommended to adjust antimicrobials to piperacillin - tazobactam 3.375 mg every 6 hours , metronidazole 500 mg iv every 8 hours , and vancomycin 125 mg po every 6 hours to cover for gut flora including clostridium difficile until it could be ruled out .\nblood cultures collected the day before discharge of the previous admission flagged as positive after 5 days of incubation in the aerobic bottle ( bactec plus aerobic / f ) , but no organisms were seen upon gram stain . however , after two days of incubation , small mucoid colonies of oxidase positive gram negative coccobacilli were seen growing on chocolate agar only . the team was notified and antimicrobials were adjusted to only piperacillin - tazobactam 4.5 g every 6 hours .\nafter an additional two days of incubation , an identification of paracoccus yeeii was made by matrix assisted laser desorption ionization time of flight mass spectrometry ( maldi - tof ms ; vitek ms ) with a match of 99.9% to the vitek ms ivd unclaimed database .\nidentification was confirmed by sequencing of the first 500 bp of the 16s gene . upon speciation ,\nthe patient was switched to ceftazidime 1 g every 12 hours to cover for p. yeeii as well as concern for a hospital acquired pneumonia .\nthe patient completed a 2 week treatment course of gram negative antimicrobial coverage with two beta lactam agents and had clinical improvement with no other culture growth of p. yeeii .\nunfortunately , the patient developed end - stage liver disease and eventually succumbed to death due to septic shock from citrobacter freundii pneumonia .\nto our knowledge , this is the first reported case of p. yeeii in a patient with cirrhosis .\npatients with decompensated cirrhosis are at high risk of infection from immune dysregulation , a heightened inflammatory response , altered gut flora , and bowel translocation .\nhowever , no causative organism is found in up to 50% of patients with decompensated cirrhosis presenting with clinical sepsis .\nthis case of bacteremia with a rare gram negative organism is instructive regarding optimal diagnosis and treatment of infection in patients with decompensated cirrhosis who have an unclear source of infection as they have an extremely high risk of morbidity and mortality .\np. yeeii is an aerobic gram negative coccobacillus that has been isolated in soil and marine sediment , and has been rarely reported as infections in humans .\np. yeeii has been identified in the past through commonly available biochemical tests , and this case demonstrates the utility of maldi - tof ms for the identification of this infrequently encountered organism , .\nthe few reported cases of p. yeeii to date have entailed peritonitis among peritoneal dialysis patients , , myocarditis in a heart transplant patient , corneal graft infection , and heart failure with bullous skin lesions .\nall cases identified p. yeeii through culture of affected tissues . only 2 cases , including ours , have been associated with bacteremia and ours is the first case of a patient with cirrhosis . the source of bacteremia in our case remains unclear , but it is plausible that the patient s lymphedema and bowel edema could be sources for this environmentally found organism . over the previous year , the patient had several episodes of bacteremia thought to be from bowel translocation including group g -hemolytic streptococci , streptococcus mitis / oralis , citrobacter braakii , and enterococcus faecium ( the patient was not on chronic antimicrobials ) .\nmaldi - tof may help with rapid diagnosis and guide appropriate treatment when initial cultures in patients with decompensated cirrhosis and clinical sepsis are negative .\nit is recommended that patients with advanced cirrhosis who develop gastrointestinal bleeding be treated empirically with third generation cephalosporins , .\nhowever , this case illustrates that uncommon gram negative organisms may not necessarily be covered with third generation cephalosporins .\nalthough we did not have antimicrobial susceptibilities performed in our case , the existing literature on p. yeeii suggests that the organism is susceptible to fluoroquinolones and beta - lactams though higher minimum inhibitory concentrations ( mics ) were reported with third generation cephalosporins .\nthis case reinforces the challenges in isolating rare infections in patients with cirrhosis . in the absence of obvious infectious sources in a patient with decompensated cirrhosis\ncollaboration with infectious disease specialists and microbiologists is warranted in these cases to isolate infectious organisms and to identify appropriate antimicrobials promptly .\nthis research did not receive any specific grant from funding agencies in the public , commercial , or not - for - profit sectors .", "answer": "highlightsno organism is found in up to 50% of infected patients with decompensated cirrhosis.in the absence of obvious infectious sources , consider rare gram negative organisms.uncommon gram negative organisms may not be covered by empiric antibiotics.maldi-tof may help with diagnosis when cultures are negative in these patients.human infections with paracoccus yeeii , a gram negative coccobacillus , is rare .", "id": 536} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvascular malformation is known as one of the major therapeutic problem even to the most experienced clinicians .\nthese malformations grow proportionately with age , and may involve multiple anatomical spaces and encase critical neuromuscular structures , associated with nerve damage , massive bleeding , and deformity .\nmanagement of arteriovenous malformations ( avms ) remains challenging because of their unpredictable behavior and high recurrence rate if treated by curettage alone without inadequate ligation of the feeder vessels .\nthese lesions are treated by variety of techniques over the years , including surgical excision , irradiation , electrocoagulation , cryotherapy , intravascular magnesium or copper needles , systemic corticosteroids , interferon- , embolization , cryotherapy , lasers and sclerotherapy .\nsclerotherapy is an effective , conservative and low cost technique for the treatment of benign vascular lesions , included vascular malformation .\nthe sclerosant agents used are 5% sodium morrhuate , sodium psylliate , quinine urethrone , 5% ethanolamine oleate , 1% polidocanol , sodium tetradecil sulfate , and hypertonic saline .\nwe present our experience in treating palatal vascular malformation using direct ethanol sclerotherapy as a cheep therapeutic modality for treatment of deeply seated vascular lesion .\ntwenty one - year old saudi male patient presented to the department of oral and maxillofacial surgery clinic at king abulaziz university complaining of swelling on the right side of the face ( figure 1a ) .\nextra - oral clinical examination revealed swelling on the right side of the face , which is soft and compressible .\nintraoral examination showed a bluish swelling at the junction of soft and hard palate that bleed easily on touch .\ncomputerized tomography ( ct ) and magnetic resonance image ( mri ) studies revealed that it is a vascular malformation that extends to the infratemporal area ( figure 2 ) .\nthe patient was advised to have ethanol directly injected into the lesion as surgical excision was hazardous and difficult to achieve .\npatient disagree with that option and disappear for 18 months and returned back with severe gingival inflammation around the whole right maxillary quadrant which appeared covered by heavy calculus as he could not brush his teeth because of bleeding that he described as extensive ( figure 1c ) .\nadvised was given to the patient that the only treatment option we can offer him is the ethanol injection .\nthe procedure and possible complications were explained to the patient and family and they agreed to that option . under general anesthesia using fibro optic intubations , as the lesion was approaching the soft palate and there was a fear that routine nasal intubations could be hazardous to the airway , contrast medium was injected toward the engorged vascular lesion using a no .\n18 venipuncture catheter ( to determine the volume of the growths before treatment ) , followed by injection of one - third to one - quarter cavity volume of 95% ethyl alcohol into the tumor cavity according to lee and chen ( figure 3 ) .\nthe patient was kept intubated for 48 h to guard his airway , as there was edema .\nintravenous dexamethasone ( 0.1 mg / kg ) was given for 3 days postoperatively to control inflammation .\npatient was discharged from the hospital on the fifth post injection day and kept follow up every week for the first three months , then every 2 weeks for another 3 months .\nthe lesion remarkably shrinks and the hygienist was able to thoroughly scale his teeth without any bleeding ( figure 4 ) . \n\nfigure 1a ) clinical picture of the patient showing facial asymmetry as result of right zygomatic swelling ; b ) intraoral view shows bluish mass extending to the soft palate when the patient presented to the clinic for the first time ; c ) intraoral photograph of the same patient 18 months after first presentation .\nthe lesion increased in size , bled easily and appeared darkens with bad oral hygiene and heavy calculus at the right side of the jaw . \n \na ) clinical picture of the patient showing facial asymmetry as result of right zygomatic swelling ; b ) intraoral view shows bluish mass extending to the soft palate when the patient presented to the clinic for the first time ; c ) intraoral photograph of the same patient 18 months after first presentation .\nthe lesion increased in size , bled easily and appeared darkens with bad oral hygiene and heavy calculus at the right side of the jaw . \n\nfigure 2a ) axial and b ) coronal computed tomography scan obtained with contrast material shows dilated vessels that extend into the infratemporal area and multiple phleboliths can be seen .\nc ) and d ) axial t2 weighted magnetic resonance image shows high intensity lesion with flow representing vessels of different sizes . \n \na ) axial and b ) coronal computed tomography scan obtained with contrast material shows dilated vessels that extend into the infratemporal area and multiple phleboliths can be seen .\nc ) and d ) axial t2 weighted magnetic resonance image shows high intensity lesion with flow representing vessels of different sizes . \n\nfigure 3a ) the catheter loaded with ethanol in place during injection ; b ) contrast medium is injected into the lesion and an x - ray is taken to make sure that the catheter is within the lesion itself ; c ) an angiogram shows ethanol injection within the lesion . \n \na ) the catheter loaded with ethanol in place during injection ; b ) contrast medium is injected into the lesion and an x - ray is taken to make sure that the catheter is within the lesion itself ; c ) an angiogram shows ethanol injection within the lesion . \n\nfigure 4a ) postoperative picture of the lesion one and b ) three months following injection . \n \na ) postoperative picture of the lesion one and b ) three months following injection .\nthere were no complications reported in this case except some palatal ulceration which is improving with every visit .\ntreatment success was determined clinically by reduction in lesion size , ability of the patient to chew and to clean his teeth without bleeding , patient experience to pain and by patient satisfaction .\nfor example : surgical excision can lead to significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding and the complicated anatomy of the face and neck , may result in significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding if surgery is adopted .\nlaser therapy presents higher costs to the patient and may result in skin atrophy , transient or permanent hyperpigmentation , slight depression of the skin and scarring .\nintralesional injection of corticosteroids may cause adrenal suppression , slowed weight gain , atrophy , and necrosis .\nthe use of sclerotherapy in the management of vascular anomalies has increased and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas .\nit has the advantage of low cost , no external scaring , and few complications compared to surgical treatment .\nvarieties of sclerosing agents have been used for the management of various vascular malformations such as 5% sodium morrhuate , sodium tetradecyl sulphate , ethanolamine oleate , ok432 , bleomycin , ethanol , and hypertonic saline , alone or in various combinations .\nabsolute ethanol was adopted as a new scleroagent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates .\nethanol is used most of often due to its low cost , antiseptic quality , wide availability and easy of use ; however , it requires general anesthesia because the procedure is very painful .\nthe aim of treatment is to eradicate the lesion nidus completely , which is the fundamental abnormality as even the smallest residual nidus may expand to form a recurrence . in the presented case it was difficult to achieve complete eradication of the lesion by surgical approach because of the possible hazards that are associated with the affected site .\nit has been suggested that ethanol cause protoplasm precipitation which subsequently causes permanent obliteration of the vessel lumen . also do et al .\nreported that ethanol has shown the ability to induce protein denaturation of the endothelial cells with subsequent vessel wall denudation and interruption , which results in the complete obliteration of the vessel lumen rather than just simple obstruction .\nalthough various complications were reported to develop during the procedure such as local skin necrosis and fibrosis , haemoglobinuria , anaphylaxis , and some major complications were rarely reported including blood loss , acute pulmonary hypertension with cardio - pulmonary collapse , therefore , lee and chin used rubber bands to compress the patient 's forehead and chin to occlude facial venous return and minimize complications , also hammer et al . recommended to inject the ethanol slowly , over a period of several minutes and not exceeding 1 cc / kg of body weight while monitoring the pulmonary artery pressure to avoid such a catastrophic situation\nalso , ethanol should only be used in the head and neck region by individuals and centers with professional expertise and experiences including maxillofacial surgeon , general radiology , general medicine , cardiovascular medicine , physical medicine and rehabilitation , dermatology , psychiatry , nuclear medicine , and social services with maximum efficiency to handle or at least minimize various anticipated complications .\nalso , careful and routine monitoring of pulmonary arterial pressure are required by the interventional radiologist , and anesthesiologist .\nvascular malformations were treated with direct percutaneous injection of absolute ethanol , which resulted in remission , and alleviation of their symptoms , with no major complications .\nthis technique provides a simple , low cost and reliable alternative treatment for venous malformation in the face and neck .\nabsolute ethanol sclerotherapy can deliver excellent results as an independent therapy to the infiltrating type of extra - truncular form of vm .\ncomplications can occur but are rare . the morbidity involved should be clearly understood and accepted by the patient and family , and the risk of acute and chronic complications , either major or minor ,", "answer": "arteriovenous malformation is treated by variety of techniques over the years . \n sclerotherapy is considered an effective and conservative technique for the treatment of benign vascular lesions and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas . \n absolute ethanol was adopted as a new sclerosant agent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates . \n sclerotherapy has the advantage of no external scaring , low cost , and few complications in comparison to the surgical treatment .", "id": 537} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nantiphospholipid syndrome ( aps ) is an autoimmune disease characterized by the presence of antiphospholipid antibodies , venous and/or arterial thrombosis , and repetitive fetal loss [ 1 , 2 ] .\nthe laboratory criteria to diagnose aps are high serum levels of lupus anticoagulant as well as anticardiolipin and -2 glycoprotein - i antibodies .\naps can occur with other systemic diseases such as systemic lupus erythematosus or as a single entity .\ndeep vein thrombosis represents the most frequent aps complication , as it occurs in 2955% of patients ; however , acute or indolent chronic ischemic presentations can involve any organ including the lung , skin , brain , liver , kidneys , adrenal glands , heart , and eyes .\nocular involvement can occur in 888% of patients [ 5 , 6 , 7 ] and it can be the first sign at presentation .\nit is therefore important to make a quick diagnosis in order to consider anticoagulant treatment to prevent further thrombosis , as the risk of this complication is up to 29% in untreated aps patients .\nvisual symptoms at presentation vary from a reduction of visual acuity and amaurosis fugax to transient scotoma and visual field defect , all of which can be unilateral or bilateral .\nit is important to underline that , when amaurosis fugax involves both eyes simultaneously , it is often a manifestation of central nervous system ischemia .\nocular discomfort , conjunctival hyperemia , and pain have often been reported in the literature as common symptoms of aps patients .\na 38-year - old female patient presented with reduced vision in the right eye , which had occurred the same day .\nthe patient had a negative ocular and medical history and no previous miscarriage as well as no relevant family history for ophthalmic pathologies .\nvisual acuity was finger count in the right eye ( 1-meter distance ) and 20/20 in the left eye .\nfundoscopic examination revealed a subhyaloid hemorrhage , engorged and tortuous retinal veins , intraretinal hemorrhages , and cotton wool spots ( fig .\n1 ) . fundus fluorescein angiography demonstrated a delayed inferior hemiretinal venous filling ( fig .\n3 ) . as choroidal ischemia has been previously reported with aps , indocyanine green angiography was performed , which did not show any significant modification of choroidal perfusion .\nprothrombotic conditions secondary to other factors such as sepsis , homocystinemia , and genetic defects of coagulation factors ( thrombin mutations , factor v leiden , antithrombin deficiency , etc . ) were ruled out .\nlaboratory investigations showed that the erythrocyte sedimentation rate , igg anticardiolipin , and -2 glycoprotein - i antibody were above normal limits .\nthromboplastin inhibition test was strongly positive for lupus anticoagulant , while antinuclear antibody and antinative dna antibodies were negative .\nserum total complement ( c3 , c4 ) , proteins s and c , and antithrombin iii were within normal limits .\nother studies were normal or negative , including complete blood count , platelet count , renal , liver , and thyroid functions , hemoglobin a1c , ferritin , transferrin , and ldl cholesterol .\nthe patient met the criteria for aps ; however , according to the american college of rheumatology classification criteria , a concomitant diagnosis of systemic lupus erythematosus could not be established .\nshe started treatment with hydroxychloroquine 200 mg / daily and ticlopidine 250 mg / daily . considering the central location of the hemorrhage , we deferred any invasive treatment and opted for watchful waiting .\nthe subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode ( fig .\nthis is the first reported case of simultaneous subhyaloid hemorrhage and branch retinal vein subocclusion as presentations of aps .\na prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis .\nthis is often difficult , as ocular manifestations of aps can be variable . assessing the patient 's thrombotic risk by investigating the presence of high blood pressure and hypercholesterolemia ,\nthe use of tobacco and oral anticontraceptive agents as well as the history of previous of thrombosis , fetal loss , and acute ischemic events is mandatory in the process of deciding whether to start systemic treatment .", "answer": "we report an atypical presentation of antiphospholipid syndrome ( aps ) with concomitant subhyaloid hemorrhage , engorged and tortuous retinal veins , intraretinal hemorrhages , and cotton wool spots in a 38-year - old female . \n medical treatment was preferred to any invasive treatment . \n the subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode . \n a prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis .", "id": 538} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncancer is one of the leading causes of death worldwide and accounted for 7.6 million cases ( 13% of all deaths ) in 2008 ; in 2013 in the united states there are 12,340 estimated new cases and 4,030 deaths by cervical cancer [ american cancer society : cancer facts and figures 2013 ] .\nmeanwhile in romania , based on statistical data from 2012 , cervical cancer is ranked third place taking in account the women cancer incidence , after the breast and colorectal cancer .\ncervical cancer develops in a multi - stage process , successively passing from a cervix with a normal epithelium to cervical intraepithelial neoplasia and finally leading to invasive cervical cancer . a relevant epidemiologic risk circumstance for the progress of the cervical cancer is represented by the presence of high risk human papillomavirus infections .\nconsequently , considerable importance has been given to the molecular premise which leads to the progression of cervical cancer .\nrnai ( rna interference ) is a natural mechanism able to specific inhibit a target gene .\nthe prospective exploitation as a therapeutic has lately been strengthened by the small interfering rna ( sirna ) delivery to human tumours .\nrnai has been demonstrated as a relevant investigation device for particular target genes by using exogenous sirnas .\nsirnas are single - stranded non - coding rnas with 2023 nucleotides length , being able to negatively modulate gene expression profile at post - transcriptional level .\nsirnas represent an encouraging novel type of medicaments for cancer therapy , as a result of targeting the mutated tumour suppressor genes or activated oncogenes .\nmany recent investigations have shown that sirna can efficiently inhibit oncogene expression in cancer cells .\nvarious investigations demonstrated clearly that the deactivation of p53 constitutes a crucial step in carcinogenesis .\nthe present study was designed to investigate the potential use of p53 rnai to block p53 expression , as well as the subsequent effect on cell invasion and gene expression on the human cervical cancer cell .\nhela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance\n, cells were cultured in dmem medium , 10% fcs ( foetal bovine serum ) , 100 u / ml penicillin and 100 mg / ml streptomycin , 2 mm l - glutamine , 1% nonessential amino acids , all purchased from sigma - aldrich , bucharest , romania . for this investigations 510 hela cells\n/ well were used for reverse - transfection , based on a preliminary optimised protocol for p53sirna , using siport neofx as transfection agent ( ambion , usa ) .\na validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations .\nsiport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability .\nwe performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by .\nthe total rna for the cells treated with 50 nm p53sirna andthe control group respectively at 24 hours post treatment was extracted using trireagent ( sigma - aldrich , bucharest romania ) based on the producer recommended protocol for each triplicate specimen .\nall of the samples had a rin ( rna integrity number ) higher than 7.5 .\nthe 8 genes selected were assessed using specific primer and upl based on in silico design . the total rna ( 500 ng ) from all the samples was reverse transcribed using the first strand cdna synthesis kit for rt - pcr ( roche , bucharest romania ) . for the gene amplification we used taqman universal pcr master mix , in a 20 l volume in a 96-well plate using the roche lightcycler 480 system .\nthe qrt - pcr reaction amplification program was as follows : 10 minutes at 95c for enzyme activation followed by 45 cycles of 15 seconds at 95c and 1 minute at 60c for the amplification step .\nthe data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene\nthe evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no .\nhela is a human cervical carcinoma cell line ; this was incubated in a 5% co2 incubator at 37c . for maintenance\n, cells were cultured in dmem medium , 10% fcs ( foetal bovine serum ) , 100 u / ml penicillin and 100 mg / ml streptomycin , 2 mm l - glutamine , 1% nonessential amino acids , all purchased from sigma - aldrich , bucharest , romania . for this investigations 510 hela cells\n/ well were used for reverse - transfection , based on a preliminary optimised protocol for p53sirna , using siport neofx as transfection agent ( ambion , usa ) .\na validated p53sirna pool ( sc-29435 , santa cruz ) was used at a concentration of 50 nm in serum starvation condition using optimem medium ( gibco , invitrogen , romania ) , in accordance with the producer recommendations .\nsiport neofx 0.25% concentration was able to achieve the maximum inhibition of target gene with no effects on cell viability .\nwe performed the invasion assays on hela cells to evaluate the impact of p53sirna treatment using the cim - plate 16 with the xcelligence rtca dp instrument ( roche applied science ) according to the described protocol by .\nthe total rna for the cells treated with 50 nm p53sirna andthe control group respectively at 24 hours post treatment was extracted using trireagent ( sigma - aldrich , bucharest romania ) based on the producer recommended protocol for each triplicate specimen . the rna concentrations and quality were assessed by the nanodrop-1100 agilent 2100 bioanalyzer spectrophotometer .\nall of the samples had a rin ( rna integrity number ) higher than 7.5 .\nthe 8 genes selected were assessed using specific primer and upl based on in silico design .\nthe total rna ( 500 ng ) from all the samples was reverse transcribed using the first strand cdna synthesis kit for rt - pcr ( roche , bucharest romania ) .\nfor the gene amplification we used taqman universal pcr master mix , in a 20 l volume in a 96-well plate using the roche lightcycler 480 system .\nthe qrt - pcr reaction amplification program was as follows : 10 minutes at 95c for enzyme activation followed by 45 cycles of 15 seconds at 95c and 1 minute at 60c for the amplification step .\nthe data analysis was carried out to compare the gene expression values for the treated and untreated groups using ct method . as housekeeping gene\nthe evaluation of the vegf protein expression at 48 hours post treatment was done using human vegf quantikine elisa kit ( r&d , catalog no .\nxcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels .\nthe cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells .\nthis data can facilitate to comprehend the response to treatment in dynamic . in figure 1\nwe can observe a delay and a reduction of the cell migration after the p53sirna treatment .\ntaqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis .\nrelative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 .\nafter 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) .\nxcelligence system is an innovative device that allows the scanning of cellular response via an impedance - based technology in real time , lacking any exogenous labels .\nthe cim - plate 16 furnishes a kinetic cell - response profile to p53sirna throughout an investigation , specifying the commencement and ratio of invasion and migration of hela cells .\nthis data can facilitate to comprehend the response to treatment in dynamic . in figure 1\nwe can observe a delay and a reduction of the cell migration after the p53sirna treatment .\ntaqman qrt - pcr assay was used to examine the effect of p53sirna on a panel of 8 genes related to apoptosis and angiogenesis . relative gene expression quantification using ct method leads to the downregulation of the selected gene , presented in the figure 2 .\nafter 48h post transfection with p53 sirna inhibition in hela cell line , vegf protein was found dowregulated in the culture medium than in the control group ( figure 3 ) .\nalthough at this moment cervical cancer is considered as a preventable disorder there is a significant risk of disease recurrence causing a persuasive necessity to research new therapeutic targets for this disease management .\nit is now well recognized that the tumour progression of all cancers is characterized by intensified proliferation and invasion rate and diminished in apoptosis . at the same time\nthe apoptosis and angiogenesis are interconnected as can be observed from figure 4 , using string.9 database .\nthe idea of this study is in agreement with the previous studies which are based on the hypothesis that once mutated , p53 exercised oncogenic role . by using sirna\nthe role of the present study is to emphasize the cooperation between oncogenic mechanisms , confirming the crosstalk between apoptotic and angiogenic mechanisms .\nthis has a significant therapeutic relevance based on the fact that mutated p53 is related to cancer aggressiveness or to promoting metastasis . in a similar study\nwas observed that , by using sirna targeting p53/p73 , tumoral cells were sensitized to chemotherapy . in a recent study , pinx1 was displayed as a novel target gene of p53 , proposing the suppression of p53/pinx1 pathway as a novel mechanism to enhance the telomerase activity in cervical cancer cells , and leading to reduction of cell proliferation .\ntargeting oncogenic signals such as the mutated p53 gene that gains oncogenic role , we observed a downregulation of specific genes involved in apoptosis but also in angiogenesis , connected with a reduction of the invasion rate in the case of p53sirna therapy .\nafter 24 hours of treatment with p53sirna we can observe downregulations of important genes involved in apoptosis and angiogenesis , as displayed in figure 2 .\nthis study confirmed our hypothesis that p53 plays a central role in carcinogenesis as displayed in figure 3 , as important therapeutic target .\np53 could promote the convergence of the apoptotic and angiogenic pathways in cervical cancer cells .\nit has been proved that p53 is able to indirectly downregulate vegf gene expression , via the retinoblastoma ( rb ) , in a p21-dependent mode , confirming its function in cell - cycle regulation as displayed by recent studies .\nthe complete comprehension of the cross - talk between p53 and angiogenic pathways represents a challenge in cancer therapy [ 2426 ] .\nanother study reveals that mutant p53 correlates with overexpression of vegf . in a similar study\nthe inhibition of mutant p53 represents a significant therapeutic target , a fact emphasized by walerych as rebel angel .\np53 gene knockdown in hela cells plays an important role not only in apoptosis but also in angiogenesis through various mechanisms that regulate tumour cell development and migration .\nthe angiogenic phenotype related to p53 targeted by sirna in human cancers is frequently associated with resistance to conventional genotoxic anticancer agents .\ntherefore , p53 inhibitions become dependent and rely on angiogenesis for growth and metastasis . the results in the current research\nmay also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing therapeutic response in a wide range of tumoral pathology .", "answer": "background and aimssirnas represent an encouraging novel alternative in cancer therapy as a result of targeting the mutated tumour suppressor genes or activated oncogenes . \n targeting oncogenic signals , as the mutated p53 gene that gains oncogenic role , we observed inhibition of migration , a downregulation of specific genes involved in apoptosis but also in angiogenesis , connected with a reduction in invasion rate in the case of p53sirna therapy.methodsthe study was designed to assess the role of p53 by using rnai ( rna interference ) in hela in vitro cell culture model . therefore cell migration rate was assessed by using xcelligence systems , gene expression for a panel of genes involved in apoptosis and angiogenesis , and validation of gene expression data at protein level.resultson the selected in vitro model p53 sirna therapy was correlated with the reduction of cell migration . \n the downregulation of p53 , pten , tnf , nfkb , bcl-2 , icam-2 , vegf , and fgfb was evidenced as response to p53 inhibition.conclusionrnai may be a valuable technology in order to restore the normal cellular phenotype . \n the results in the current research may also have an important significance outside the context of cervical cancer , by using specific inhibitors for p53 for increasing the therapeutic response in a wide range of tumoral pathology .", "id": 539} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacademic failure is a serious problem of the students , educational system , and society .\nusually the students who have experienced academic downfall during their education do nt demonstrate desired theoretical or practical capability of their lessons .\nacademic downfall can also result in numerous emotional , social , behavioral , and psychological problems ; a study in the united states showed that the main reason for the suicide in students is downfall in education or profession .\nconsidering the above - mentioned points , it can be said that academic downfall is one of the major problems of educational systems ; hence that every year it causes the dissipation of a large number of the labor force and economic sources and has serious consequences for students , their families , and society in general .\nthus , taking the suitable steps to solve this problem is fundamental . in this study ,\nthe role of personality traits and mental health were considered as determinant factors in academic failure .\nhaving good mental health and healthy personality , are necessary for each person in order to concentrate , learn , and study .\npersonal characteristics such as gender , age , degree of education and field of education are also important factors in this respect . in doing so , some pieces of research that have been conducted to determine the role of psychological factors in academic downfall are introduced .\n, their study pointed out that the student with lower levels of achievement has a higher risk of psychological disorder .\nbentez et al . in a study concluded that increased period of education comes along with the lack of health .\nmc ilroy and bunting , king and bailly , they said that personal characters have a relationship with educational achievement of student .\nchamorro - premuzic and furnham , gray and watson , duff and boyle , oconnor and paunonen , they said that loyalty and prepending are among the strongest and the most resistant 's characters related to educational achievement .\nwalt and pickworth reported that those students had higher achievement who had the following characteristic loyalty , emotional stability , social skills , self - disciplined , practical and were calm or anxious to an imagination .\n, come to the conclusion that hopefulness and positive attribution style were the higher predictive factors in educational achievement .\nin separate conducted studies , revealed that there is a significant relationship between age and academic performance .\nhazavehei et al . , safdari - dehcheshmeh et al . , and zare et al .\nin separate studies , concluded that academic performance of female students was better comparing to the males .\nsince mental health is regarded as a basic requirement for satisfactory performance in any field , including educational therefore investigation is so important that the national institute of mental health believes that those with mental health can satisfy their needs and have more compatibility with others .\nmental health can also affect personality traits , the ability of social interaction , and adaptability to new situations .\nit 's worth mentioning that educational status is one of the many needs that can be influenced by mental and individual features .\nthus , considering the importance of medical sciences , the significant role of students personal and psychological state in their educational performance , and the consequences of academic downfall , this study aim to determine the role of personal and psychological factors in academic downfall among the students of medical sciences . concerning the variables of mental health and personality traits ,\nstudies carried out within the country and outside of the country have investigated the roles of different variables in educational performance .\nfor example , in order to determine personality traits , the following tests and questionnaires were used for different majors and semesters : cattell 16 personality factor ( 16 pf ) , izeng personality test , personality a and 5 , minnesota multiphasic personality inventory ( mmpi ) long and short form and in order to evaluate the mental health gho , symptom checklist-90 ( scl-90), .\nwere used questionnaire , neo - personality inventory revised ( neo - ff - r ) , minnesota long and short personality test forms mmpi and for testing students mental health , scl-90 , general health questionnaire ( ghq ) , and etc . , were used .\ntherefore , different results were obtained all of which indicate that some of the personality traits and mental health indicators influence students academic performance\n. therefore , in this study , the effect of interaction between personal factors , personality characteristics and mental health indicators of students , in statistical model analyzes . the present study attempts to answer the following hypothesis : if personality factors , the status of metal health and demographic features have any role in predicting the educational performance of the students in the isfahan university of medical sciences .\nthe present descriptive - correlation study was conducted among 771 students who entered isfahan university of medical sciences between the years 2005 and 2007 .\nthe students educational and clinical files were used , and psychological interviews were performed by a clinical psychologist ( for communication and psychological support ) .\nthe psychological data were completed using ghq test ( known tool for the screening ) : somatic symptoms , anxiety - insomnia , social dysfunction , severe depression , and personality test minnesota short form ( mmpi ) ( this questionnaire forms , can be used in psychological and clinical research ) : hypochondriasis , depression , hysteria , psychopathic deviate , paranoia , psych asthenia , obsessive - compulsive disorder , schizophrenia , hypomania .\ndemographic characteristics included gender , age and education . in order to access the students grade point average students ( gpa ) and their scores in different subjects ,\nan agreement was reached by the department of education , to use sama software ( 2003 , iran ) , which included all the students educational information .\nit 's worth mentioning that the students information was confidentially analyzed in a group . using ( version 15 , spss inc . , chicago , il )\nmost of the participants in the present study were females ( 81.2% ) , 97% were single and 46.04% were bachelor students ( 27.62% undergraduate and 26.32% ph.d .\nthe average students standardized score in all the scales of personality tests was normal and in the range of 4752 .\nin addition , the average students score in all the general health indices was normal .\nthe score of social performance had a higher average compared with others . in response to the following hypothesis analysis,[tables 13 ] .\nthe prediction of educational performance of the students at isfahan university of medical sciences based on personality indicators , mental health , and individual characteristics the investigation of the significance of the predictive coefficients in educational performance of the model the coefficients of variables of the predictors of educational performance if personality factors , the status of metal health and demographic features have any role in predicting the educational performance of the students in the isfahan university of medical sciences . according to the above results ,\nthe variables that are mentioned in the model could predict 11% of students educational performance ( students average scores have been considered ) as follows : education 4% , age 4% , gender 2% , depression ( as one of the aspects of mmpi test ) 1% , and hypochondria ( as one of the aspects of mmpi test ) 1% . as it has shown in table , the predictor coefficients of education , age , gender , depression , and hypochondria for educational performance is significant ( p < 0/0001 ) . according to the results shown in table 3 , five variables that could predict educational performance , in priority , are education , age , gender , depression , and hypochondria .\nthe analysis of the results showed that education , age , gender , depression , and hypochondria are the predictive variables of educational performance ( students average scores have been considered ) . according to the obtained results , among all the personality , general health , and demographic variables , only the variables of education , age , gender , depression , and hypochondria are significant predictors of students educational performance . concerning the prediction of students educational performance based on their age\n, it should be said that the results of this study verify the results of the studies of duff and boyle no contradictory result were found .\nconcerning prediction of educational performance based on the depression ( as one of the aspects of mmpi test ) , it 's worth mentioning that the results of this study are verifying those of the following studies ; raoofi et al . , the results of predicting based on mental health are in agreement with the results of the following studies ; rafati et al .\nthese results were in contradiction to just one study by farahbakhsh et al . in 2007 , based on prediction of educational performance , according to mental health .\nconcerning the relationship and prediction of the educational performance based on hypochondria ( as a part of the mmpi ) , only kahrzaei et al .\nconfirmed the results of the present study ; but if the relationship between some of the personality features and educational performance is taken into account , the following studies could be mentioned as those that verify and recognized some personality traits as related factors in educational performance .\nchamorro - premuzic and furnham , gray and watson , duff and boyle , walt and pickworth , leeson et al .\nthe results of the present study did not confirm the results of the study done by karamimatin according to which no significant relationship was observed between personality traits and educational performance .\nthe results of the regression test showed that the depression could predict 1% of the variance of academic performance .\ndepression occurs among students for many reasons , but the aim of this study is not saying about these reasons . when depression for whatever reason , was formed , academic performance of students most likely to be affected .\nit is not needed to mention that academic achievement requires concentration , high morale , planning , perseverance , and many other factors that can be negatively influenced by depression .\nalthough depressed students understand the importance of academic success and feel penitent if they experience academic failure , they are unable to compensate them academic downfall . in the present study , hypochondria\nsometimes pressures , lack of satisfaction , and the guilty conscience appear as physical illnesses .\npeople are differently afflicted with different illnesses or disorders based on their potential , genetic background , and the skills that can be learned .\nsome of these disorders overlap the others , and some can cause the others . in general , fear of getting sick can reduce solace , concentration , and accomplishment . in fact , there is no disease , but it feels odor one may have wrong feelings about the severity of illness or pain . considering psycho - physics and the connection between body and mind , the effects of body on mind and vice versa can not be denied .\nconsidering the prediction of educational performance based on gender , it should be mentioned that the results of the present study are in agreement with those of the following studies ; leeson et al . , and in contradiction to the following studies which have not found any relation in this area with those ; raoofi et al .\nresearch , in which each variable was analyzed separately , all variables were analyzed in a more advanced model in this study .\nmost of the studies have confirmed that female students have more academic achievements than male students .\nthis difference has been probably caused by the following reasons . \n in terms of culture girls\nare expected to be less concerned with diversity , mainly concentrate on their lessons and academic achievement , and spend less time on recreational , social , and political activitiesin our society boys are disappointed in academic achievements .\nthey feel that they should find a job as soon as possible due to the importance of financial issues and continue their education puts off their occupational success .\nhence , they do nt have enough motivation to make any attempts and usually their aim is just to get an academic degree . \n in terms of culture girls\nare expected to be less concerned with diversity , mainly concentrate on their lessons and academic achievement , and spend less time on recreational , social , and political activities in our society boys are disappointed in academic achievements .\nthey feel that they should find a job as soon as possible due to the importance of financial issues and continue their education puts off their occupational success .\nhence , they do nt have enough motivation to make any attempts and usually their aim is just to get an academic degree .\ncourses have their own special characteristics to which the students should adapt , such as the obligation to study more , study more difficult lesson , spend more time studying ( those who do nt have enough time to study will be anxious about their lessons ) , length of the educational period , fatigue that causes limited recreational activities , and constant involvement with lessons that leads to low - spirit , lack of energy , or losing motivation .\nbeing unsatisfied with the future career among students who are aware of the long period that they have to spend on education can affect academic performance , too .\nthe present study also revealed that the older the students get , the lower their academic performance will be ( as a result of research dastranj et al . , 2012 ) .\nthe influence of age on academic performance can be viewed from different perspectives : ( 1 ) as the students get older , they are faced with some problems like entering higher semesters , more difficult lessons , more assignments , and higher expectations of their supervisors .\nthis can lead to fatigue , impatience , or lack of motivation because of the long period of academic educations .\n( 2 ) as the students get older , they approach the age at which they should accept more personal and social responsibilities , and they have to make important choices in marriage or , continuing education , job and , etc .\ntherefore , they have to spend some of their energy and concentration to choose the right path .\nlearning , gpa , and studying well are more important to the students in the first semesters .\nfirst time failed in studies , and the first conditional state , or a low gpa can cause a lot of negative feelings in person , but as time passes , these conditions become something usual and are accepted more easily .\nmaking friends with some people who are not committed to their education can worsen this situation .\nwe can say , if a student suffers from a physical or psychological problem , he / she has less opportunity in learning , education , and academic success .\nthis can lead to academic failure . \n performing check - up and consulting sessions for identifying students problems , especially males , older , and higher level students who are more vulnerable , according to this studycontinuous psychological intervention for the students who have a higher risk , following preventive measures in accordance to the compiled educational protocols and the target students characteristics . \n performing check - up and consulting sessions for identifying students problems , especially males , older , and higher level students who are more vulnerable , according to this study continuous psychological intervention for the students who have a higher risk , following preventive measures in accordance to the compiled educational protocols and the target students characteristics .\n\n performing check - up and consulting sessions for identifying students problems , especially males , older , and higher level students who are more vulnerable , according to this studycontinuous psychological intervention for the students who have a higher risk , following preventive measures in accordance to the compiled educational protocols and the target students characteristics . \n performing check - up and consulting sessions for identifying students problems , especially males , older , and higher level students who are more vulnerable , according to this\nstudy continuous psychological intervention for the students who have a higher risk , following preventive measures in accordance to the compiled educational protocols and the target students characteristics .", "answer": "background : the issue of students academic failure is one of the most important educational , economic , and social issues . \n cognizance of the factors related to academic downfall is so efficient in its prevention and control and leads to protecting governmental assets and labor force . in order to achieve this goal , this study intends to determine the predictive factors of the students academic performance in isfahan university of medical sciences in terms of their personality profile , mental health , and their demographic characteristics.materials and methods : this study was a descriptive - correlation study on 771 students who entered isfahan university of medical sciences between 2005 and 2007 . \n the information was gathered through using the students educational and clinical files ( for measuring personality characteristics and mental health ) and sama software ( to get the mean scores ) . \n minnesota multiphasic personality inventory short form and general health questionnaire were used for collecting clinical data . \n the data were analyzed using spss 15 ( stepwise regression coefficient , variance analysis , student 's t - test , and spearman correlation coefficient).result : the results showed that the aforementioned students obtained a normal average for their personality profile and mental health indicators . \n of all the reviewed variables , education , age , gender , depression , and hypochondria were the predictive factors of the students educational performance.conclusion:it could be concluded that some of the personality features , mental health indicators , and personality profile play such a significant role in the students educational life that the disorder in any of them affects the students educational performance and academic failure .", "id": 540} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nigg4-related diseases are systemic syndromes characterized by elevated serum levels of igg4 and igg4-positive lymphoplasmacytic infiltrative lesions in the body .\nit was first observed that mikulicz 's disease correlated with igg4-related disease and later determined that igg4-related disease can occur in any ocular adnexal tissues [ 25 ] .\nhere , we review the clinicopathological features , differential diagnosis , and treatments of orbital igg4-related disease on the basis of a meta - analysis of 42 patients including 3 case series studies .\nthe median age of patients with orbital igg4-related disease is 59 years ( range : 30 to 86 years ) with a 1 : 1 male - to - female ratio [ 35 ] .\nnotably , there is a 1 : 3 for bilateral lacrimal lesions similar to finding in mikulicz 's disease .\nalthough orbital igg4-related disease can occur in men and women of any age , many patients have a history of allergic diseases such as asthma and allergic rhinitis . \nthe signs and symptoms of orbital igg4-related disease are chronic lid swelling ( figure 1 ) and proptosis ( figure 2 ) , but otherwise there are only mild signs , or no signs of inflammation or periocular pain .\nocular motility is restricted mildly if at all , despite the presence of one or more enlargements of the large extraocular muscles ( figure 1 ) .\nthere are generally no visual disturbances , although they may occur due to apical orbital lesions ( figure 2 ) .\nimaging studies show infiltrative lesions in ocular adnexal tissues such as the lacrimal glands ( figure 1 ) [ 25 ] , extraocular muscles ( figure 1 ) [ 3 , 4 ] , infraorbital nerves ( figure 2 ) , optic nerve sheath , lacrimal sac , and even cavernous sinus ( figure 2 ) or the intracranial extension . in cases of orbital igg4-related disease\n, 62% have bilateral lesions , 69% have lacrimal gland involvement , and 48% have bilateral lacrimal gland involvement [ 35 ] .\npatients with orbital igg4-related disease sometimes have systemic igg4-related lesions in their submandibular glands ( 29% ) , lymph nodes ( 14% ) , pancreas ( 5% ) , or bile ducts ( 5% ) [ 35 ] .\nigg4-related lesions in the thyroid and pituitary may also be present [ 7 , 8 ] .\nchronic rhinosinusitis with orbital igg4-related lesions has similar histology ( figure 3 ) , although nonspecific chronic rhinosinusitis can be also associated with igg4-positive plasma cells in the lesions .\nlaboratory data of patients with orbital igg4-related disease show elevated serum levels of igg4 and ige , as well as hypergammaglobulinemia [ 25 ] .\nhigh igg4 levels are associated with elevated levels of the soluble interleukin ( il-2 ) receptor .\nsclerosing pancreatitis and cholangitis , considered as igg4-related diseases , have lymphocytes that signal for il-4 and il-10 in situ .\nalthough an etiology for the igg4-related group of disease has been not determined yet , one plausible hypothesis for these serological and immunological abnormalities is that they result from in vivo activation of the immune system by activated th2 cells [ 3 , 10 ] .\nthe histology of orbital igg4-related disease includes different degrees of lymphoplasmacytic infiltration with dominant sclerosing lesions or reactive lymphoid follicle ( reactive lymphoid hyperplasia , figure 3 ) [ 25 ] .\nrarely , orbital igg4-related disease may have an infiltration by lymphoplasmacytic cells and macrophages containing eosinophilic material .\nigg4-related diseases in the body are characterized histologically by obliterative phlebitis ; however , it is rare in orbital igg4-related disease .\nimmunohistochemical analysis shows igg4-positive plasma cells ( figure 3 ) , which differentiate igg4-related disease from other inflammatory conditions arising from the ocular adnexa [ 3 , 4 ] .\nfor optimal treatment and resolution , orbital igg4-related disease must be differentiated from the following : idiopathic orbital inflammation , idiopathic orbital myositis , marginal zone b - cell lymphoma , antineutrophil cytoplasmic antibody- ( anca- ) mediated systemic vasculitis ( such as churg - strauss syndrome and wegener granulomatosis ) , and reactive lymphoid hyperplasia without igg4-positive plasma cells ( figure 4 ) .\nthey are characterized by sudden onset of orbital inflammation , periocular pain , swelling and redness of the eyelids , proptosis , ptosis , and ocular motility restrictions .\nhowever , some cases of idiopathic orbital inflammation have atypical signs and symptoms , that is , they have lacked acute onset and inflammatory signs . in such cases ,\nocular adnexal marginal zone b - cell lymphomas make up the majority of lymphomas arising from the ocular adnexa .\nthey are characterized histologically by the presence of reactive follicles in up to 64% of cases , sclerosis in up to 20% of cases , and plasma cells in up to 35% of cases .\nin addition , 9% of patients with ocular adnexal marginal zone b - cell lymphomas have infiltration of igg4-positive plasma cells and elevated serum level of igg4 .\nevidence of light chain restrictions by in situ hybridization and immunoglobulin heavy chain gene rearrangements by southern blot analysis can differentiate between marginal zone b - cell lymphomas with igg4-positive plasma cells and igg4-related inflammatory disorder .\nocular adnexal lymphomas are reported to arise in igg4-related sclerosing dacryoadenitis , indicating a possible link between the two conditions .\nthe symptoms of patients with orbital lesions include periocular pain , which can differentiate these patients from those with orbital igg4-related disease\nthus , anca - related vasculitis may not only include nonspecific inflammatory lesions , but also have abundant igg4-positive plasma cells .\nfinally , mikulicz 's disease includes symmetrical bilateral lacrimal gland enlargements and frequently correlates with igg4-related disease .\nhowever , symmetrical bilateral lacrimal gland enlargements do not always indicate igg4-related lesions ( figure 4 ) .\ntreatments for patients with orbital igg4-related diseases may include systemic steroids , radiotherapy , or rituximab [ 35 ] .\nstudies of each of these treatments involved relatively few patients , making it difficult to evaluate the treatment outcomes via meta - analysis .\norbital igg4-related diseases resolve after systemic steroid therapy , but relapse is often observed following therapy discontinuation . in mikulicz 's disease , relapses of lesions are observed when steroids were discontinued .\ntherefore , it may be best to continue prednisolone at 5 to 10 mg / day or to combine prednisolone with an immunosuppressant such as azathioprine .\nrituximab treatment leads to prompt clinical and serologic improvement in patients with refractory igg4-related diseases , although recurrence is also observed after rituximab treatment ends in some patients with orbital igg4-related disease .\norbital igg4-related disease has several unique characteristics that distinguish it from other orbital inflammatory conditions .\norbital igg4-related disease differs from other igg4-related diseases in the body in that it arises from nonglandular lesions and is not associated histologically with obliterative phlebitis .", "answer": "orbital igg4-related disease , which can occur in adults of any age , is characterized by igg4-positive lymphoplasmacytic infiltrations in ocular adnexal tissues . \n the signs and symptoms include chronic noninflammatory lid swelling and proptosis . \n patients often have a history of allergic disease and elevated serum levels of igg4 and ige as well as hypergammaglobulinemia . \n orbital igg4-related disease must be differentiated from idiopathic orbital inflammation and ocular adnexal marginal zone b - cell lymphoma to ensure appropriate and effective treatment . \n systemic steroid therapy decreases the size of the lesions , but relapse often occurs when systemic steroid therapy is discontinued .", "id": 541} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\naccidents and injuries are part of daily events , and many of these injuries are initially treated by untrained personnel due to lack of health care providers on the accident site .\ntherefore , implementing correct first aid measures is vital for victims in emergency cases and helps to improve the overall outcome of the first aid process in emergency situations .\nthe national first aid science advisory board defined first aid as making an assessment and implementing interventions that can be performed by a bystander ( or by the victim ) with minimal or no medical equipment .\nseveral studies have been conducted around the world to evaluate the level of knowledge about first aid among different groups including university students .\nsome studies showed that a high percentage of students in different countries lack the appropriate first aid knowledge .\nsimilarly , different studies showed that the immense majority of peoples had little or no first aid training .\nmany factors had been shown to be associated with better knowledge , including taking a first aid course during school , having a driving license , or having a higher level of education .\nfew reports assessing the first aid knowledge were carried out in arab countries and most of them reported that university students have poor levels of first aid knowledge . to the best of researcher 's knowledge and experience , no studies have been conducted about general first aid knowledge in jordan .\nthis gives the research a unique importance in building the cornerstone of the research background in the jordanian context .\ntherefore , first aid basics will equip persons around the injured person to reduce the danger posed by the accident and can make the difference between life and death in these situations .\nhence , the current study has aimed at evaluating the level of knowledge about first aid process among university students in jordan .\nthis cross - sectional study was conducted among university students in the large public university in the north of jordan using simple random sampling and involved administering a questionnaire .\nthe study included 1500 students from the total 14 colleges at yarmouk university , jordan between september and december of 2014 .\ninclusion criteria for participation involved : be an enrolled student at yarmouk university and be a jordanian citizen .\nthe newly drafted questionnaire was presented to a reviewer panel composed of three members for refinement and re - wording of questions to ensure that statements were understandable and meaningful to the participants , and to ensure that the questionnaire consistently measured what it was intended to measure .\nreliability of the surveying instrument was determined by using the internal consistency method . after administering the questionnaire used in this study ,\ncronbach 's alpha coefficients for all domains were produced and ranged from 0.77 to 0.91 indicating that the items within each domain are consistent in measuring the same attribute .\nthe final questionnaire was composed of four sections : demographic characteristics of students ( 7 items ) , general first aid knowledge ( 6 items ) , first aid knowledge in various emergency situations ( 17 items ) , and attitudes toward first aid education ( 2 items ) .\nthe total number of questionnaire items was 25 questions in addition to the 7 demographic characteristics . to ensure maximum representativeness ,\nquestionnaires were handed out to students during the general university requirement classes in which students from all faculties and specializations are registered after getting permission and obtained 15 min out to fill the questionnaire .\nparticipants completed a multiple - choice questions and questions required short answers on their level of knowledge about first aid .\nall data were analyzed using spss ( version 20 for windows ) ( spss statistics for windows , version 20.0 .\narmonk , ny : ibm corp ) . frequency distribution and descriptive criteria were calculated .\nthe study was approved by the ethics committee at the faculty of medicine / yarmouk university , jordan and granted the number 30/2014 .\nthis cross - sectional study was conducted among university students in the large public university in the north of jordan using simple random sampling and involved administering a questionnaire .\nthe study included 1500 students from the total 14 colleges at yarmouk university , jordan between september and december of 2014 .\ninclusion criteria for participation involved : be an enrolled student at yarmouk university and be a jordanian citizen .\nthe newly drafted questionnaire was presented to a reviewer panel composed of three members for refinement and re - wording of questions to ensure that statements were understandable and meaningful to the participants , and to ensure that the questionnaire consistently measured what it was intended to measure .\nreliability of the surveying instrument was determined by using the internal consistency method . after administering the questionnaire used in this study ,\ncronbach 's alpha coefficients for all domains were produced and ranged from 0.77 to 0.91 indicating that the items within each domain are consistent in measuring the same attribute .\nthe final questionnaire was composed of four sections : demographic characteristics of students ( 7 items ) , general first aid knowledge ( 6 items ) , first aid knowledge in various emergency situations ( 17 items ) , and attitudes toward first aid education ( 2 items ) .\nthe total number of questionnaire items was 25 questions in addition to the 7 demographic characteristics . to ensure maximum representativeness ,\nquestionnaires were handed out to students during the general university requirement classes in which students from all faculties and specializations are registered after getting permission and obtained 15 min out to fill the questionnaire .\nparticipants completed a multiple - choice questions and questions required short answers on their level of knowledge about first aid .\nall data were analyzed using spss ( version 20 for windows ) ( spss statistics for windows , version 20.0 .\narmonk , ny : ibm corp ) . frequency distribution and descriptive criteria were calculated .\nthe study was approved by the ethics committee at the faculty of medicine / yarmouk university , jordan and granted the number 30/2014 .\na total of 1500 questionnaires were distributed to students of which 1116 ( 74.4% ) were returned . about 20% of the returned questionnaires were incomplete for which they had to be excluded , leaving a total of 883 questionnaires valid for statistical analysis .\nof the 883 questionnaires included in the final analysis , 34.1% participants ( n = 301 ) were males and 65.9% ( n = 582 ) were females .\nthe average ( standard deviation ) age of members of the sample group was 19.9 ( 2.6 ) years .\nmost of the respondents were undergraduates ( 99.3% , n = 877 ) compared with only 0.7% ( n = 6 ) postgraduate students .\nthe majority of students were studying at literary colleges ( 59.3% ) , 31.4% of scientific colleges , 6.3% of physical education college , and the remaining 2.9% were studying in health sciences .\nin the general knowledge domain , which asked about the correct civil defense call number , vital signs normal values or limits , and the normal blood sugar , students were more knowledgeable about normal body temperature and the civil defense call number .\nthe percentage of students who reported correct answers about vital signs and other general information are described in table 1 .\nfrequency and percentage of students who reported correct answers about vital signs and other general information as per gender about 80% of students gave correct responses of the normal body temperature , however , less than half of students knew the normal pulse rate ( 48.2% ) and normal blood sugar values ( 46.5% ) .\nonly a small percentage of students knew the respiration rate and normal blood pressure values .\nthe overall knowledge of first aid in different emergency situations has revealed that participants were more knowledgeable when asked about the position of patients in cardiopulmonary resuscitation ( cpr ) and care in case of bleeding ; however , they were least knowledgeable when asked about the correct position in coma situations and care of stabbing wounds .\nparticipants correct responses about the care of victims in various emergency situations are shown and ranked in table 2 .\nfrequency and percentage of students who reported correct answers about the care of victims in various emergency situations as per gender only gender , faculty , and having previous first aid experience were significantly associated with first aid knowledge .\nfemale students were more knowledgeable than male students in all aspects of first aid knowledge which revealed significant statistical associations .\ntable 3 describes the significant associations between the previous experience of students and correct responses of their level of first aid knowledge .\nsignificant associations between previous experience of students and correct responses of their level of first aid knowledge having previous first aid experience was significantly associated with a better level of first aid knowledge among students when they were asked about vital signs ( body temperature , pulse , respiration , and blood pressure ) , correct position in case of coma , correct site of doing cardiac messages , how to check pulse in case of coma , burn care , and care in stabbing wounds . with respect to faculty background , several significant statistical associations have been revealed .\nsignificant associations between faculty of students and percentages of correct responses of their level of first aid knowledge remarkably , health sciences students were more knowledgeable about first aid care in all emergency situations .\nhowever , students from the scientific colleges were more knowledgeable than students from other colleges when asked about the correct emergency call civil defense number .\nthe last two questions in the questionnaire asked students whether the media in jordan offer enough information about the care or first aid for the situations mentioned in the questionnaire and whether students think that first aid course and training should be handled at secondary schools in jordan . about three - quarters of students thought that the media does not offer enough first aid information , and about 97% of students believed that first aid course and training should be handled at secondary schools .\nno similar studies evaluating the level of first aid knowledge among university students in jordan exist so far .\nresults of the current study reveal the inability of the majority of the students surveyed to provide efficient first aid in emergency cases .\neven with respect to simple questions ( e.g. , normal values of the pulse , respiration rate , the number of mouth - to - mouth ventilation or chest compressions in cpr ) , there are a large number of students , even among those trained in first aid , presenting serious lacks of basic first aid knowledge .\ninterestingly , students were less knowledgeable about the correct respiratory rate in an adult in 1 min .\nonly about 11% of the participants knew the correct respiratory rate . however , respiration is one of the most crucial vital signs of an individual .\nsimilarly , al - khamees ( 2006 ) reported that university students in kuwait have poor levels of first aid knowledge .\nthis result is supported by the results of an indian study , which revealed that 11.5% of male students and 15.4% of female students had a good level of knowledge on first aid measures .\nhaving previous first aid experience was strongly associated with better first aid knowledge of students .\nfurthermore , in greece , hatzakis et al . supports this result showing that trained industry workers on first aid were more knowledgeable than nontrained workers .\na similar trend was noted among university students in pakistan . moreover , a study conducted in austria demonstrated that the monstrous greater part of individuals had next to zero first aid preparing and that there was an immediate relationship between the level of emergency treatment preparing and the nature of first aid measures taken by the general population who attended accidents .\nstudents from the health sciences and scientific colleges had better first aid knowledge compared to students of literary and sport colleges . in jordan , joining health sciences or scientific colleges requires students to get higher averages in the high school which indicates the better academic performance of those students .\nthis notion may explain the difference in knowledge between the health sciences and scientific colleges from one side and students from other colleges on the other side .\nhowever , in fact , health sciences college is just starting at yarmouk university , and the last batch of students is still in the 1 year during which general university requirements are taught rather than core health sciences courses .\ntherefore , the low study year may explain this lack of knowledge among students of health sciences college . despite the relatively large sample size ( n = 883 ) ,\nthe researcher acknowledges the limitation of this study regarding reliable generalization of results to the whole population of university students in jordan as the total participants in this particular study were sampled from a single university .\ndespite the relatively large sample size ( n = 883 ) , the researcher acknowledges the limitation of this study regarding reliable generalization of results to the whole population of university students in jordan as the total participants in this particular study were sampled from a single university .\noverall , first aid knowledge among students at yarmouk university was considered to be insufficient . to decrease the early mortality and morbidity of accidents and emergencies ,\nfirst aid should be a standard component and separate course of educational programs introduced at secondary school and college levels as well as in the media .\nfurthermore , first aid course should be updated at regular intervals throughout different study levels .\nthe knowledge deficit of first aid measures among university students is evocative that only a minority of people have adequate emergency treatment preparing .\nit is suggested that all adults should be able to administer first aid since everyone is expected to experience emergency situations at any time .", "answer": "background : this study has aimed to evaluate the level of knowledge about the first aid process among the university students in jordan.methods:the study population consisted of students of the 14 scientific and unscientific faculties at yarmouk university , jordan . \n data were obtained via questionnaires from 883 students.results:the majority of participants were females ( 65.9% ) with mean age ( standard deviation ) of 19.9 ( 2.6 ) years . \n only 29.2% of students had previous first aid experience . \n when asked , only 11% of students knew the normal respiration rate of an adult in 1 min . \n results revealed that female students , having previous first aid experience , and being a student of the health sciences and scientific colleges were the only factors had significant statistical associations with better level of first aid knowledge.conclusions:the students knowledge about first aid is not at an adequate level \n . it would be advisable that first aid course be handled as a separate and practical course at secondary school level .", "id": 542} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbariatric surgery is most often performed with the laparoscopic roux - en - y gastric bypass ( lrgb ) .\nlrgb has favourable effects such as weight loss and correction of metabolic disturbances , but is also associated with serious complications .\nit is a severe complication , which can lead to massive bowel necrosis that may result in short bowel syndrome ( sbs ) and sometimes death .\npregnant women , who have previously undergone lrbg , represent a diagnostic challenge when presenting with acute abdomen and internal hernia in this setting might be particularly risky . in this case , we present a 22-year - old woman , who had undergone lrgb and who suffered a massive internal hernia during pregnancy leading to short bowel syndrome .\nin january 2012 , at 26 weeks of gestation , a 22-year - old woman was admitted to our surgical department due to sudden onset of upper abdominal pain .\nthe patient was otherwise healthy and had at the time she became pregnant lost 50 kg following a lrgb done two years and 11 months earlier .\nfollowing admission , an acute ultrasound showed gall bladder stones , and a mri scan showed no definite signs of internal hernia but could not demonstrate gallstones . due to severe pain\na trans - cystic balloon dilation of the papilla of vater was done as the cholangiogram demonstrated poor drainage caused by small gallstones in the common hepatic bile duct . on the 5th postoperative day\nshe was re - operated due to cholascos with renewed cystic duct ligation and drainage . on the following day , endoscopy was performed because of hematamesis , with the finding of blood in the jejunum , but no specific bleeding site was identified .\nthe clinical condition worsened and she was transferred to the intensive care unit ( icu ) with severe septicaemia and acute respiratory distress syndrome ( ards ) . on day 13 , a laparotomy was performed . an internal hernia through petersen 's space with necrosis of 1 m jejunum starting 10 cm below the pouch - enteric anastomosis\na vital premature girl of 1020 g was delivered by caesarean and the necrotic intestine was removed .\nsecond and third look operations were performed the next days with further small bowel resections leaving her with a saliva fistula 10 cm below the pouch - enteric anastomosis , a jejunostomy 15 cm from the ligament of treitz and a blind closed ileum 35 cm from the ileo - coecal valve ( fig .\n1 ) . after 3 months in the icu and surgical ward with several other complications , such as infectious complications , pneumothorax , thrombosis of the superior mesenteric vein as well as the iliac veins and a exposed bowel parquet covered with split skin ,\nthe patient had a good appetite and enjoyed the meals , but obviously she had no absorption of food due to the very short fistula below the pouch - enteric anastomosis . through a central venous line ( hickmann catheter ) she initially received 2200 kcal and later when she increased her daily activities this\nwas increased according to 2700 kcal given as smof kabiven ( fresenius ) added with vitamins and trace elements , and in addition 3 l of isotonic saline to maintain the fluid balance .\nalso in this phase complications occurred , and the hickmann catheter eventually had to be removed due to a yeast infection with candida albicans .\nthe nutrition was thereafter delivered through a peripherally inserted central venous catheter ( piccline ) . after four months of hospitalization\nthe patient was discharged with home parenteral nutrition . in november 2012 , ten month after the internal herniation , intestinal continuity was reconstructed , and a defect having a width of up to 12 cm in the anterior abdominal wall was closed with bilateral partial component separation technique ad modum ramirez .\nthe patient insisted on trying without parenteral nutrition , and 10 weeks later , she was doing well .\nher weight had increased 2 kg since the operation , she had 12 bowel movements a day and blood values for haemoglobin and albumin had increased as well .\nthis patient suffered from massive small bowel internal hernia with extensive bowel resection leading to sbs dependent on parenteral nutrition during her pregnancy .\nthe patient was left with an intact duodenum , 15 cm of jejunum , 35 cm of ileum and her colon .\ninitially she was treated with 100% parenteral nutrition , but after reconstructive surgery with re - established intestinal continuity the amount of parenteral nutrition was rapidly reduced , and after six weeks she was weaned off parenteral nutrition .\nseveral cases of internal hernias during pregnancies have been reported and three maternal deaths have been described .\ndescribe severe internal hernias in pregnant women , involving the entire small intestine , parts of the colon and in renault et al .\nshe underwent extensive bowel resection leading to an acute intestinal failure associated with severe complications ( type 2 intestinal failure ) .\nafter treatment in a specialized intestinal failure unit , she underwent a long and complicated rehabilitation period and was discharged with a short bowel syndrome treated with home parenteral nutrition and fluids ( type 3 intestinal failure ) , and she survived . to our knowledge , no pregnant woman with lrgb has previously survived an internal herniation with such massive bowel necrosis as in this case , see table 1 .\nthe university of nebraska medical center describes in a series of papers that 5 out of 210 patient with postoperative sbs had previous gastric bypass operation , and thereafter they scrutinized 9 patients with sbs that had bariatric surgery performed . in a more recent paper , they reviewed 9 cases with massive bowel resection during pregnancy leading to small bowel syndrome .\nit is believed to be caused by the growing uterus , which increases the intra - abdominal pressure , or postpartum as the uterus rapidly decreases in size .\nthe surveys of series of patients with previous bariatric surgery demonstrate that up to 16% of the patients develop internal herniation .\nmost bariatric surgeries have been performed in women of reproductive age , and as lrgb increases fertility , complications during pregnancy are to be expected . it is suggested that the changed anatomy during pregnancy disposes for herniation to occur . during pregnancy , the cause of abdominal pain can be difficult to diagnose , with potentially fatal consequences for both mother and foetus .\nit is most important that relevant tools such as mri or ct scans are not postponed .\ninterpretation of mri and ct scan can be difficult especially in pregnant women , thus laparoscopy should be performed on a wide indication , when there is clinical suspicion of internal hernia and laparotomy performed if the anatomy is not clear . in the present paper\nthe literature provides other successful reconstructions after lrgb complicated with internal obstruction . a case report of a 44-year - old woman , who suffered from volvulus after lrgb , leaving her with an intact duodenum\nthe younger age of our patient leaves her with an even better chance to stay off parenteral nutrition .\nsince internal hernia is potentially life threatening for mother and foetus , both obstetricians and abdominal surgeons must be aware of this condition and surgery should be performed on a wide indication .\nwhen bowel necrosis is found it should be resected and in case of extensive bowel resection the patient should start parenteral nutrition , and an evaluation should be made in centres specialized in intestinal failure .\nall authors have contributed to acquisition of data , analysis and interpretation of data , writing , drafting the article and revising it critically for important intellectual content and approved of the final version .\nwritten informed consent was obtained from the patient for publication of this case report and case series and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .", "answer": "introductionbariatric surgery is most often performed with the laparoscopic roux - en - y gastric bypass . \n a complication to the laparoscopic roux - en - y gastric bypass is internal hernia , which occurs in up to 16% of the patients . \n since the laparoscopic roux - en - y gastric bypass is performed in women of fertile age , internal hernia may occur during pregnancy.presentation of casea 22-year old woman with a history of laparoscopic roux - en - y gastric bypass suffered from massive internal hernia during pregnancy with widespread bowel necrosis . \n extensive surgery was performed leaving the patient with an intact duodenum , 15 cm of jejunum , 35 cm of ileum and colon . \n parenteral nutrition was initiated and ten months after the internal hernia , intestinal continuity was re - established . \n ten weeks later the patient reached parenteral nutrition independence.discussioninternal hernia after laparoscopic roux - en - y gastric bypass can be difficult to diagnose , especially during pregnancy and might be severe and life threatening for both mother and child.conclusionobstetricians and abdominal surgeons must be aware of this condition . \n surgery should be performed on a wide indication . when bowel necrosis is found it should be resected and in case of extensive bowel resection the patient should be evaluated in centres specialized in intestinal failure .", "id": 543} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnecrotising fasciitis ( nf ) is a serious soft tissue and life threatening infection , primarily involving the skin and superficial fascia , characterised by a rapid and extensive necrosis of the subcutaneous tissue .\nmost patients have associated comorbidities , such as diabetes , hiv infection or treatment with immunosuppressive drugs , but it can also affect previously healthy individuals .\ninfection is one of the common causes of morbidity and mortality in patients with systemic lupus erythematosus ( sle ) .\nit is associated with immunosuppressive agents , renal failure , and increased disease activity . despite the increased propensity of sle patients to develop common and opportunistic infections , nf has rarely been reported . to our knowledge\n, only 31 cases are described in the literature to date ( see table 1 ) .\nnf has also been described in other rheumatic diseases including polymyositis , dermatomyositis , systemic sclerosis , rheumatoid arthritis and ankylosing spondylitis , but it appears that this association is more common in sle.1 \n 2 clinical features of nf in systemic lupus erythematosus a , asian ; aa , african american ; aps , antiphospholipid syndrome ; art , arthritis ; avn , avascular necrosis ; aza , azathioprine ; cad , coronary artery disease ; cs , corticosteroid therapy ; cyc , cyclophosphamide ; d , died ; dm , diabetes mellitus ; f , female ; fg , fournier 's gangrene ; h , hispanic ; hcq , hydroxychloroquine ; lym , lymphocytes ; m , male ; mmf , mycophenolate ; mtx , methotrexate ; n , nephritis ; na , not available ; nf , necrotising fasciitis ; pe , pulmonary embolism ; rtx , rituximab ; s , survived ; sa , staphylococcus aureus ; ttp , thrombotic thrombocytopenic purpura ; wbc , white blood cells .\nwe describe the case of a nf caused by pseudomonas aeruginosa , complicated by recurrent sepsis and multiorgan failure in a young patient with a history of sle .\na 26-year - old asian woman with a complex history of sle , diagnosed at age 14 years when she presented with malar rash , arthralgia , mouth ulcers , pulmonary vasculitis , strongly positive anti - nuclear antibody and anti - dsdna antibodies .\nsubsequently , she had idiopathic detrusor overactivity with repeated urinary tract infection . linked to her corticosteroid treatment she developed avascular necrosis of her elbow ( at that time , on prednisolone 6 mg daily ) .\nthe patient was also treated with hydroxychloroquine ( hcq ) , azathioprine ( aza ) ( 100 mg from 1999 to 2009 ) and had 14 courses of cyclophosphamide ( cyc ) ( a cumulative dose of 14 g ) and two of rituximab ( rtx ) ( two 1 g intravenous infusions separated by 2 weeks ) , the last being given in march 2012 for a sle flare manifested by severe vasculitic rash . immediately prior to b - cell depletion , her c3 level was 0.33 g / l ( normal : 0.651.65 ) , cluster designation ( cd ) 19 count was 0.146/l ( 0.110.69 ) , and immunoglobulin g level was 23.4 g / l ( 716 ) . in may 2012\n, she presented to her local hospital with painful swelling of her left lower limb , she denied a history of trauma , and her inflammatory markers and ultrasonography were normal , and she was discharged . within 12 h\nshe was found at home with a glasgow coma scale of 6 , and was admitted to the intensive care unit ( icu ) . on examination ,\nthe patient was in septic shock with hypotension ( systolic blood pressure 60 mm hg ) , tachycardia ( 135/min ) , and respiratory failure ( sao2 70% ) .\nlaboratory results showed erythrocyte sedimentation rate 96 mm / h ( normal : 17 ) , c - reactive protein 281 mg / dl ( 05 ) , white blood cells 15 400/l ( 300010 000 ) ( 97% neutrophils ; 1.9% lymphocytes ) , haemoglobin 9.6 g / dl ( 11.515.5 ) , platelet 50 000/l ( 150 000400 000 ) , na 138 mmol / l ( 135145 ) , creatine kinase 474 iu / l ( 26140 ) , urea 16.8 mmol / l ( 1.78.3 ) , alamine transaminase 384 iu / l ( 1035 ) , total bilirubin 11 mg / dl ( 0.31.9 ) , albumin 17 g / l ( 3450 ) , creatinine 290 mol / l ( 4992 ) and proteinuria 2.30 g / l ( 00,10 ) .\nher c3 level was 1.0 g / l ( 0.651.65 ) , cd19 count was 0.001/l ( 0.110.69 ) , and immunoglobulin g level was 9.32 g /\ncultures of muscle tissue only grew p aeruginosa , resistant to piperazillin - tazobactam ; therefore , she was treated with meropenem , teicoplanin and clindamycin . as her clinical condition\nhowever , 1 week later , she deteriorated , with thick yellowish sputum , fever , respiratory distress and the chest x - ray showed right consolidation .\nciprofloxacin and teicoplanin were empirically started , and the patient 's clinical condition gradually improved . a week\nafter this treatment had finished , the patient became worse with a new left lower lobe consolidation , so the antibiotic therapy was changed to ceftazidime .\nher lupus flared with a marked malar rash over both cheeks , so her steroids ( prednisolone ) were increased to 20 mg per day and hcq was restarted .\nshe was in the icu from may to august 2012 , but made a remarkable recovery and was discharged home with a steroid - tapering regimen and hcq .\nlater , she developed two more sle flares , which were treated again with cyc and rtx , achieving good response . at 18 months\nfollow - up , there is no evidence of new recurrent or severe ongoing infections .\nmost patients with nf ranged from 38years to 44 years , with a male to female ratio of 23 : 1 , and apparently an increased incidence in african and asian countries.3 the true incidence is not known ( it is estimated to be approximately 0.4 cases per 100 000 ) , with a reported mortality from 20% to as high as 80%.35 the causative agents of nf vary and include two main categories , polymicrobial ( type 1 ) and infection of group a streptococcal ( type 2 ) .\npatients with sle have an increased risk of infections , due to immunological dysfunction and the use of steroids and immunosuppressive agents.6 other factors , such as the presence of a variant form of the fc receptor are also believed to contribute to the risk of pneumococcal infection.7 nf due to pseudomonas has very rarely been reported.8 \n 9 the clinical presentation of patients with nf may be deceptively benign at onset , and it may not be possible to distinguish it clearly from minor soft tissue infections .\nour patient was discharged from the original hospital before being admitted subsequently severely ill to university college hospital .\nthe lesion was rapidly progressive , probably due to her sle , and the prolonged steroid treatment and recent administration of cyc and rtx might have increased the risk of infection . during the initial period ,\nexploration of the wound may be necessary even before the diagnosis is clear , particularly in a patient who is clearly toxic .\nin addition to the present case , the other 31 cases of nf in sle patients that have been reported are summarised in table 1 .\nthe ages ranged from 12 years to 66 years , and 27 ( 84% ) were female .\nmost of the patients reported were asian ( 33% , 7 patients ) , 33% ( 7 patients ) hispanic and 19% ( 4 patients ) african american .\nthe sites of infection included the upper or lower limb ( 60% , 17 patients ) , the face , neck or tongue ( 18% , 5 patients ) , the genital area ( 11% , 3 patients ) and the abdomen ( 11% , 3 patients ) .\nnf type 1 was identified in 22 patients ( 71% ) and type 2 in 7 patients ( 23% ) , and when reported , the most common isolation was streptococcus ( 50% , 16 patients ) .\nmost of the patients presented with intense pain , poorly demarcated erythematous , swollen lesions over the limbs and systemic inflammatory response ; 28 patients ( 88% ) were receiving corticosteroids and 7 hcq ( 22% ) . additionally , use of other immunosuppressive drugs has been reported ( 5 cyc , 5 aza , 2 rtx , 1 mycophenolate , 1 methotrexate , 1 plasmapheresis ) before or at the time of infection .\nother associated conditions have been identified , including nephritis ( 54% ; 15 patients of 28 reported ) , either during the current presentation or in the past , 13 ( 42% ) had active disease ( presumably those taking > 20 mg prednisolone or equivalent per day ) , 76% ( 13 of 17 reported ) had lymphopenia , 100% ( 12 out of 12 reported ) low serum albumin levels and 12 ( 37% ) had anaemia . interestingly , before the admission , 9 ( 28% ) reported a previous episode of infection : urinary , bartholin abcess , diarrhoea , respiratory tract infection , carious tooth , colitis , hepatitis c , cutaneous ulcers ( 2 ) , breast abscess and diverticulitis .\nmost patients responded to therapy , but 8 of the 32 patients died ( 25% ) , probably due to the infection or because of complications ( such as sepsis or pulmonary embolism ) .\nthe case presented here and the literature reviewed suggests that active disease , nephropathy , lymphopenia , anaemia , low serum albumin levels , immunosuppressive therapy and significant infections in the past , may constitute risk factors for the development of nf in patients with sle .\na high index of suspicion for the diagnosis is required , and surgical exploration should not be delayed , especially during the early stages , to improve the prognosis of this devastating complication .", "answer": "necrotising fasciitis ( nf ) is a rare infection of the subcutaneous tissue , known to be rapidly progressive and potentially fatal . \n patients with systemic lupus erythematosus ( sle ) may be predisposed to this condition , and early clinical recognition can be difficult . \n we report a case of necrotising fasciitis in a 26-year - old woman with sle . \n she presented with painful swelling of her left leg , then developed clinical features of septic shock . \n emergency debridement was performed . \n intraoperative findings revealed nf and cultures grew pseudomonas aeruginosa . \n the patient survived after a lengthy hospital admission , following several further debridements complicated by recurrent chest sepsis and multiorgan failure . \n we also review and discuss the published cases of nf in sle patients .", "id": 544} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na level of pain that completely incapacitates one individual may cause only a minor annoyance in another .\ncharacterizing the genetic factors affecting susceptibility to chronic pain could lead to novel treatment or prevention strategies , which are desperately needed . a recent paper by costigan et al . \nthe authors performed a multi - dimensional analysis using rat gene expression and human genetic association that identified a new genetic factor affecting susceptibility to chronic pain .\nthis study was initiated by analysis of gene expression changes within rat dorsal root ganglia obtained after nerve damage was induced in three different models of chronic pain .\nthe mrna for a potassium channel alpha subunit ( kcns1 ) was constitutively expressed in sensory neurons , but was downregulated after three types of nerve injury in these models .\nother studies have successfully identified a human genetic susceptibility factor on the basis of a candidate gene emerging from analysis of a rodent model .\ncostigan and colleagues therefore examined snp alleles within the human homolog ( kcns1 ) in five independent cohorts ( two with chronic low back pain , two after limb amputation and one after mastectomy ) that have a high incidence of chronic pain . in four of\nthe five cohorts studied , there was a significant association of the val allele at a nonsynonymous snp ( rs734784 , val / ile ) with increased risk for chronic pain .\nfor example , homozygous val / val individuals had a 2.4-fold increased relative risk of failing to achieve pain improvement 1 year after back surgery .\nthe proportion of individuals without phantom limb pain after leg amputation was 45% in those without the val allele , but fell to 22% in val / val homozygotes . among healthy volunteers that were subjected to multiple experimental pain stimuli ,\nalthough experimental studies demonstrating an allelic effect were not presented , which is a substantial limitation of this study , these results make it likely that kcns1 alleles contribute to susceptibility to chronic pain .\nalthough kcns1 by itself does not have potassium channel function when tested in heterologous expression systems , its expression has been shown to modulate the currents formed by other channels [ 3 - 5 ] .\nvoltage - gated potassium channels have important effects on neuronal function , including altering the resting membrane potential and the shape and frequency of the action potential\n. similarly , gain - of - function mutations in the nav1.7 sodium channel cause syndromes associated with increased pain sensitivity .\nchronic pain has a huge impact on our society , and its treatment is a major driver for the increasing cost of health care . an estimated 76 million people in the us have chronic pain , which costs the us public over $ 100 billion per year .\napproximately 25% of chronic pain is neuropathic ( caused by nerve damage ) , which is characterized by spontaneous pain that is burning or stabbing in nature .\nthis can develop after limb amputation , mastectomy or lower back injury , or in individuals with a long history of diabetes .\nalthough multiple kinds of treatment can be used , they often have limited efficacy , and chronic pain is often managed by administration of opioids ( morphine and related synthetic compounds , including hydrocodone ) .\nthe increased focus on pain management resulted in a six - fold increase in the per capita sales of prescription opioid medications in the us between 1997 and 2006 .\nhydrocodone - acetaminophen is prescribed over 100 million times per year in the us , which is far more than any other medication , including lipid - lowering and blood - pressure - lowering agents .\nthis has led to a dramatic increase in the incidence of opioid misuse , emergency room visits due to opioid analgesic poisoning , and fatal opioid overdose .\nprescription opioids have now surpassed marijuana as the drug that is most commonly abused among the newly initiated .\nbecause of the enormity of this public health problem , we desperately need new approaches for the prevention or treatment of chronic pain conditions .\nit is likely that genetic discoveries can lead to new approaches for chronic pain , because genetic discoveries have catalyzed new approaches for related clinical conditions .\nfor example , haplotype - based computational genetic analysis has identified causative genetic factors affecting analgesic medication and inflammatory pain responses , and it has identified four genes affecting narcotic drug responses [ 11,14 - 16 ] in mice .\nthe latter genetic discovery generated a new treatment strategy for preventing narcotic drug withdrawal symptoms , which was shown to be effective in humans .\nmoreover , the variable response to multiple classes of analgesic medications among inbred mouse strains was shown to be due to genetic variation within a genetic locus ( kcnj9 ) that also encodes a potassium channel ( girk3 ) .\nhopefully , characterizing the functional role of kcns1 in neuronal responses and pain perception , and the impact of the allelic differences , could lead to new approaches for treatment of chronic pain .\nalthough the tractability of kcns1 ( or other potassium channels ) as a therapeutic target remains to be determined , small molecules targeting potassium channels have been produced ( reviewed in ) , and one has attenuated neuropathic pain in animal models . although the kcns1 val allele explains only a small percentage of the total variance ( 4.6 to 7.8% ) in the chronic pain endpoints in the cohorts studied , the identification of an initial genetic factor for chronic pain is an important achievement for two reasons .\nfirst , it shows that genetic factors can be identified for this condition , and this study provides a template for subsequent studies .\nsecond , it is likely that a greater percentage of the genetic susceptibility to chronic pain can be explained by combining this genetic factor with other subsequently identified factors .\nmoreover , pain is a subjective sensory symptom ; it is difficult to measure ; and there are substantial psychological and emotional components that contribute to the perception of pain .\nit has recently been found that there are different subtypes of chronic pain , which are distinct from the causative disease ( diabetic neuropathy , radicular back pain and so on ) .\nit is likely that genetic factors determine whether a chronic pain syndrome will develop and the specific subtype that emerges after exposure to a triggering cause .\nthus , the impact of a single genetic factor could be much larger if a specific pain subtype is examined relative to that measured in a large cohort of individuals with different types of chronic pain .\nbeyond finding new drug targets , identification of genetic factors affecting susceptibility to chronic pain syndromes could be the lever that drives advances in this difficult clinical area .\na genetic risk factor could have a substantial impact on clinical practice because individuals at increased risk for developing a chronic pain syndrome could be identified before a surgical procedure or immediately after a traumatic incident . the genetic information could be used to develop proactive methods for prevention of chronic pain syndromes , enabling interventions to be targeted to the high - risk subset . because of the great inter - individual variation in the response to painful stimuli and to analgesic drugs , knowledge of genetic risk factors could enable better stratification of chronic pain patients or aid in the selection of the appropriate therapy . rather than focusing on the disease that is etiologically associated with the chronic pain ,\nstudy is hopefully one of the first of many subsequent genetic studies that could lead to entirely new ways to approach chronic pain syndromes .\nclearly , the clinical and research communities have a long way to go before genetically targeted therapies for chronic pain become a reality .\nhowever , kcns1 ( or other channels ) could perhaps become the next target for a new class of analgesics that are selectively used in the 20% of the population that are homozygous for the val alleles of kcns1 .\nthe day might soon come when we no longer think of ' chronic pain ' as a single clinical entity , but have the tools to characterize the specific ' channelopathy ' that underlies the clinical presentation and targeted treatments for each subgroup .\ngp is a professor and mz is the director of statistical research in the department of anesthesia at stanford university medical school .", "answer": "a recent publication that combined rat gene expression data and a human genetic association study has identified the first genetic risk factor for chronic pain in humans . in four of \n the five cohorts studied , there was a significant association of an allele within a gene ( kcns1 ) encoding a potassium channel ( kv9.1 ) with an increased risk for chronic pain . \n identification of genetic risk factors for chronic pain could catalyze new advances in this difficult clinical area that has become a major public health problem . \n genomic - medicine - based advances for chronic pain could include the development of a mechanism - based classification system for chronic pain , new treatment options , improved methods for treatment selection and targeted prevention strategies for high - risk individuals .", "id": 545} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nduring 20092010 , serum samples from patients with suspected dengue were received by the fdoh for dengue diagnostic testing ; the samples came from 16 of florida s 67counties .\nspecific , real - time rt - pcr ( 8) and igm anti - denv elisa ( 9 ) . samples with highly positive rt - pcr results were spread onto cultured ae .\nalbopictus c6/36 cells , and the presence of virus and genome were confirmed by immunofluorescence ( 10 ) and rt - pcr , respectively ( 11 ) .\nisolates were further propagated and viral rna was extracted from culture supernatants by using the universal biorobot system ( qiagen , valencia , ca , usa ) .\nthe envelope glycoprotein ( e ) gene was amplified ( technical appendix ) , and the e gene open - reading frame ( 1,485 bp ) was sequenced .\nmultiple sequence alignments were performed by using the muscle module available in mega 5 ( www.megasoftware.net ) .\nevolutionary history was inferred by using maximum likelihood and phylogenetic trees constructed by using neighbor - joining methods .\nevolutionary distances were computed , and several e gene sequences from genbank were included in the phylogenetic tree to support tree topology by genotype ( technical appendix ) . in 2009 , five denv-1positive cases were identified by rt - pcr in key west .\nsubsequently , in 2010 , the fdoh tested 195 serum samples by real - time rt - pcr .\nfifty - six ( 29% ) samples were positive for denv rna : denv-1 ( 37 [ 66% ] samples ) , denv-2 ( 13 [ 23% ] samples ) , denv-3 ( 3 [ 5% ] samples ) , and denv-4 ( 3 [ 5% ] samples ) .\nmonroe county submitted 73 serum samples , of which 31 ( 42% ) had results positive for recent dengue infection : denv-1 was detected in 22 by rt - pcr , and 9 had positive igm anti - denv elisa results .\nnone of the denv-1 patients from monroe county had a history of recent travel to a dengue - endemic region before the onset of symptoms .\nfifteen other florida counties submitted serum samples : 13 counties submitted < 10 specimens , 1 submitted 2030 specimens , and 1 submitted > 60specimens .\ndenv-1 was found in 15 serum samples from 6 of these counties ; however , all the patients had a history of recent international travel .\nwe sequenced the e gene of 12 denv-1 strains isolated in florida during 20092010 to determine their genetic relatedness ; of the 12 strains , 8 were from key west and 1 each was from dade , broward , orange , and pinellas counties .\nin addition , 23 denv-1 e sequences published in genbank , including the 2010 key west isolates obtained from a blood donor and a mosquito pool ( 6,7 ) , were used to construct a maximum - likelihood phylogenetic tree .\nthis phylogenetic analysis showed that all the florida denv-1 isolates belong to the american african genotype ( genotype v ) ( 12,13 ) together with other viruses isolated throughout the americas ( figure 1 ) . \nmaximum - likelihood phylogenetic tree of dengue virus type 1 , including isolates from key west , florida , usa , and representative isolates from 5 genotypes with global geographic distribution .\nsolid circles , 8 key west viruses ( monroe county ) isolated during 20092010 ; solid diamonds , isolates from other florida counties ( dade , pinellas , orange , and broward counties ) .\neach taxon represents a single virus isolate and is labeled with the geographic origin and collection year .\nthirty - six envelope glycoprotein gene sequences obtained from genbank were included to support tree topology and identify genotypes . all genotypes except the american african genotype ( v ) have been collapsed .\nkey west denv-1 viruses grouped among central american viruses , which configure a distinct lineage separate from the caribbean viruses .\nthis divergence between the central american and caribbean lineages is well supported by high bootstrap values .\nmoreover , the key west and monroe county viruses grouped together and indicated a distinct sublineage supported by a high bootstrap value ( 99% ) , separating them from viruses isolated in dade , orange , pinellas , and broward counties that were more closely related to other central american viruses ( figure 1 ) .\none 2009 isolate ( iq425062 ) from a key west patient is related to this group , suggesting a separate introduction of denv-1 in key west .\nthe sequence similarity between the 2009 and 2010 key west strains was < 0.9% ; however , the evolutionary distance and taxa positions between the 2009 and 2010 strains presented in the phylogenetic tree suggests that the 2010 strains diverged from the 2009 strains .\nthe observed differences between e gene sequences for the key west strains ( 20092010 ) and the rest of the strains in this phylogeny were < 2.1% with the other florida strains , < 1.2% with central american strains , and < 4.8% with the rest of the american african genotype .\nevolutionary distances and the topology of the central american lineage suggest this lineage is the genetic origin of the florida denv-1 strain .\nmost viruses isolated in monroe county diverged from the central american lineage into a distinct sublineage the key west denv-1 strain associated with the 20092010 outbreak .\nthe high level of genetic similarity among the viruses isolated in monroe county , their close evolutionary distances , and the lack of recent international travel for the case - patients suggest endemic transmission and microevolution of this denv .\nconversely , the scattered and separate phylogenetic positioning of virus strains from patients with travel - associated cases from other florida counties indicates a different origin from the majority of key west isolates .\nalthough the 2009 broward isolate ( jq425067 ) is positioned near the central american lineage , the low bootstrap value ( 53% ) does not support lineage ancestry .\nthe epidemiologic and phylogenetic evidence suggests that the 2010 cases appeared to be a continuation of the 2009 outbreak . unlike cases along the texas mexico border ( 14 ) ,\nin addition , denv-1 was detected in a blood donation from the monroe county in 2010 , further supporting local transmission of denv ( 7 ) .\ncollectively , these findings indicate that endemic denv-1 was transmitted in key west over a period of > 2 years .\ntable showing the dengue virus type 1 ( denv-1 ) envelope gene reverse transcription pcr and another showing denv-1 strains used in a study of the genetic relatedness of dengue viruses in key west , florida , usa , 20092010 .", "answer": "sequencing of dengue virus type 1 ( denv-1 ) strains isolated in key west / monroe county , florida , indicate endemic transmission for > 2 years of a distinct and predominant sublineage of the american african genotype . \n denv-1 strains isolated elsewhere in florida grouped within a separate central american lineage . \n findings indicate endemic transmission of denv into the continental united states .", "id": 546} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrickettsia are obligatory , intracellular , small gram - negative bacteria associated with eukaryotic hosts .\nthey are traditionally divided into three groups : the spotted fever group , the typhus group and the scrub typhus group .\nthe spotted fever results from a large group of tick- , mite- and flea - borne zoonotic infections that are caused by closely related rickettsiae .\nrickettsia conorii has been identified as the agent causing mediterranean spotted fever ( msf ) .\na variety of geographically distinct types of r. conorii have been described that cause variable clinical presentations different from typical msf .\na 27-year - old primigravida with a 16week history of amenorrhea and respiratory failure was transfered to a tertiary care center .\nshe had high - grade fever for 8 days prior to the transfer and had developed an erythymatous maculopapular rash on day 4 of the illness , involving the trunk initially , later extending to the palms and soles [ figure 1 ] .\nerythematous maculopapular rash in a hand a persistant dry cough , not associated with hemoptysis , was noticed on day 5 .\nshe developed a progressively worsening dyspnea with bilateral ankle edema not associated with oliguria or orthopnea .\nher condition deteriorated rapidly , warranting intubation for respiratory failure and transfer to a tertiary care center . on admission to the tertiary care center icu ,\nthe patient also had tachycardia ( 128 beats / min ) without any significant st segment changes on the ecg .\nthe blood urea measured 8.7 mmol / dl with a serum sodium of 140 meq / l and a pottasium of 5.0 meq / l .\nfull blood count showed neutrophilia of 78% in a total of 14.4 10 l. hemoglobin was 7.4 g / dl with a mild thrombocytopenia of 160,000 l .\nthe blood picture revealed normochromic normocytic anemia with no evidence of disseminated intravascular coagulation ( dic ) . the international normalized ratio ( inr ) was 0.96 .\nthe serum glutamate oxaloacetate transaminase ( sgot ) activity was 42 u / l and serum glutamate pyruvate transaminase ( sgpt ) activity was 28\nthe c - reactive protein ( crp ) level was 6 mg / dl and the antinuclear antibody ( ana ) was negative .\nchest x - ray on day 1 at icu , showing diffuse bilateral opacities the patient was started on oral azithromycin , iv cefotaxime , iv hydrocortisone 50 mg 6 hourly .\nthe patient 's condition deteriorated rapidly on day 3 of icu stay and needed adrenaline , noradrenaline , dobutamine and vasopressin to maintain a blood pressure of 70/50 mmhg .\nthe urine output dropped and the urine microscopic examination revealed granular casts and dysmorphic red blood cells .\nblood urea rose to 12.9 mmol / dl and the electrolytes showed pottasium level of 5.6 meq / l .\non the 4 day at the icu and 12 day of the disease , she devoloped anuria with further increase in blood urea and serum creatinine .\nshe was hemodynamically unstable with a blood pressure of 60 mmhg even with total inotrope support .\nendocardium of the heart showed vegitations on a narrowed mitral valve [ figure 4 ] .\nthe kidneys were of normal size , but the cortico - medullary demarcations were less clear .\nthe grossly hemorrhagic lung the heart showing narrowing and vegetations at the mitral valve the histology of the lung showed gross hemorrhage and foci of pneumonia .\nthe vegetations of the heart were reported as fibrinous with entrapped white cells , but with no bacteria or fungi .\nhistology of the liver revealed centrilobular necrosis with a tendency to confluence , and a mild fatty change .\na final diagnosis of disseminated r. conorii infection with pulmonary hemorrhage , endocarditis and tubulointerstitial nephritis was made .\nr. conorii is an obligate , intracellular , slow - growing , gram - negative bacterium belonging to the spotted fever group of rickettsiae .\nunusual rickettsial strains related to r. conorii have been described as belonging to an r. conorii complex which includes the indian tick typhus rickettsia ( atcc vr-597 ) with r. conorii subsp .\nit is transmitted to humans through the bite of dog ticks ( rhipicephalus sanguineus ) widely prevalent among the old world .\nit is also known to be transmitted by haemaphysalis ticks , especially in pakistan and kenya .\nthe infection is transmitted via larvae and nymphs , and the tick bite is usually not felt .\nthe incubation period ranges from 3 to 15 days depending upon the route of rickettsial entry and the rickettsial load .\nafter introduction into the skin at the site of the tick bite or through the conjunctiva contaminated by blood or excretions from an infective tick , the primary multiplication occurs . in the skin , the localized multiplication of the rickettsiae in the endothelial cells of the capillaries leads to the formation of a raised red papule .\nthe inflammation and thrombosis of the affected capillaries lead to necrosis of the center of the papule and the formation of the typical red lesion with a black center , the tache noire .\nthis is followed by the spread of infection through lympho - hematogenous routes throughout the body , causing disseminated vascular lesions in multiple organs .\nabout 6% of the cases are severe , and fatal cases occur even in young , healthy adults , with a reported death rate of about 2.5% .\nold age , alcoholism and glucose-6-phosphate dehydrogenase ( g6pd ) deficiency are known risk factors for severe disease .\nthe patient described here is from kotagla , a tea estate village in central sri lanka .\nthe patient reported a history of significant exposure to stray dogs , abundant in any sri lankan village , but not of any tick bites .\nthe absence of the tachy noire is significant in this case as the clinical diagnosis of msf ( caused by r. conorii subsp .\nhowever , the absence of tache noire has been noted in israeli spotted fever caused by r. conorii subsp .\nthe fever starts after an incubation period of 7 days followed by a febrile period ( up to 40c , usually continuous ) associated with a maculopapular rash .\nthe papules of the rash are first noticed on the 3 to 5 day of illness , and they come out in crops and are palpable as small nodules in the skin . in severe cases ,\ncharacteristically , the rash involves the palms of the hands , the soles of the feet and , to a lesser extent , the face . in this patient ,\nthe rash involved the palms and soles , sparing the face , and was of dusky cyanotic appearence with prominant macules .\nthe cough and the dyspnea reported in our patient were relatively rare in a case series of msf , with a representation of 10% and 21% , respectively .\nrenal insufficiency is a known complication in around 6% of the patients and is caused by tubulointerstitial nephritis .\nmyocarditis had been obseved in 11% of patients and might explain the severe tachycardia with poor response to inotropes in this patient .\nthe diagnosis of r. conorii infection in this patient is justfied as there is a compatible clinical picture along with a single titer of > 1/512 .\nendocarditis is not described as a complication of r. conorii infection . identifying r. conorii as the causative organism of endocarditis in this patient\nis supported by the absence of previous heart disease and lack of clinical features to suggest subacute bacterial endocarditis on admission and during prenatal clinics .\nthe vegetations isolated from this patient as well as the blood cultures did not reveal bacteria or fungi .\nthis patient was correctly started on oral azithromicin and intravenous chlorampenicol at the tertiary hospital .\na diagnostic scoring system with microbiological , epidemiologic , and clinical parameters has been proposed for msf and it had shown good sensitivity and specificity .\nthis case highlights the need of clinical suspicion of uncommon diseases based on the geographic and socioeconomic background of a patient .\nrelatively benign diseases may have severe manifestations resulting in fatality ; therefore , physicians should consider there factors for early diagnosis and intervention .", "answer": "rickettsial diseases are common in srilanka . \n the spotted fever group of rickettsiae presents in many ways , including very severe disease causing significant morbidity and mortality . a regional variation of the rickettsia conorii subspecies and differences in clinical presentations \n are reported . \n this case describes disseminated rickettsia conorii infection in a pregnant woman presenting with endocarditis .", "id": 547} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsarcomas are mesenchymal neoplasms with various lines of differentiation , i.e. , fibrocytic , myogenic , neurogenic , vascular , chondro - osseus , or undefined .\nit is a spindle - cell tumor composed of collagen - rich and myxoid parts .\nlgfs prefers subfascial soft tissue layers on the trunk and proximal extremities in younger adults but can also develop in internal organs .\npediatric cases have also been reported.[13 ] herein , we present a 48-year - old female patient who developed a lgfs on the lower leg .\nthe clinical presentation , histopathology , surgical treatment , and follow - up are discussed .\na 48-year - old woman was referred to our department because she had developed a slow - growing plaque below the left knee for 2 years .\non examination we found an otherwise healthy , slim , woman with a symptomless firm subcutaneous plaque of about 2 cm size on the anterior aspect of the left lower leg figure 1.there was some bluish discoloration and circumscribed ulceration but no erythema or warmth .\n( a ) overview and ( b ) the ulcerated honeycomb - like plaque routine laboratory tests were unremarkable .\nthoracic dual - energy x - ray and abdominal and lymph node ultrasound excluded a metastatic spread .\nhistology revealed a spindle - cell tumor , with mild atypia and fibroblast - like morphology [ figure 2 ] .\ncells were arranged in a whorled or plexifiorm pattern , with alternating collagenous stroma and myxoid zones .\nthe tumor was surgically removed with a wide safety margin ( > 3 cm ) .\nthe defect was covered by a mesh graft transplant covered by vacuum - assisted closure ( vac ; kci international ) [ figure 3 ] .\ncompression stockings were prescribed to protect the transplant and prevent leg edema . a regular follow - up for at least 5 years\n( a ) overview ( h&e , 4 ) and ( b ) detail ( h&e , 40 ) surgical procedure . ( a ) wide excision of suprafascial soft tissue ;\n( b ) mesh graft transplantation ; and ( c ) placement of microporous white sponge for vacuum - assisted closure above the transplant\nlgfs is a very rare and distinctive type of fibrosarcoma that was first described by evans in 1987 .\nthere is a discrepancy between the bland histologic features with sparse mitotic figures and absent or mild nuclear and cellular pleomorphism and the anaplasia . the hyalinizing spindle - cell tumor with giant rosettes\nis considered a subtype of lgfs.[13 ] the tumor is further characterized by t(7;16)(q34;p11 ) translocation and fusion of fus and creb3l1 genes .\ntumor cell phenotype is positive for vimentin , ema , cd99 , and bcl-2 , but negative for cd34 , sma , s-100 , desmin , keratins , neuron - specific enolase , and cd177 .\nthe differential diagnosis includes other types of sarcomas , myxoma , neurofibroma , peripheral sheath tumor , histocytoma , desmoid tumor , and others .\nthe diagnosis often is delayed - mainly because the patients do not seek treatment early .\n( 2000 ) reported that in 15% of patients a histologic diagnosis was delayed by > 5 years . in our case\nalthough the histopathologic features suggest a low - grade malignancy , local recurrence is seen in more than 50% of patients and metastasis occurs in 6% of patients .\ntumor cell dormancy is responsible for very late metastasis in some patients , with 45 years being the longest period observed between primary surgery and metastasis .\ncomplete surgery with wide margins ( > 3 cm ) is the most important procedure .\nwe used a combination of mesh graft transplantation and vacuum - assisted closure to cover the large defect .\nit has been demonstrated recently that such a combination , with microporous sponge for vacuum - assisted closure , results in a significantly improved take rate .", "answer": "a 48-year - old female with an atypical plaque - like lesion of the lower leg is presented in this article . \n histologic investigation revealed a rare low - grade fibromyxoid sarcoma ( pt1a cn0 cm0 ; stage ia ) of suprafascial localization . \n staging of the patient did not reveal metastatic spread . \n the tumor was surgically removed with wide safety margins . \n the defect was closed using a mesh graft transplant and vacuum - assisted closure . \n healing was complete . \n regular follow - up for at least 5 years is recommended . besides the rareness of this tumor \n , this case is also remarkable because of the localization on the lower leg and the suprafascial soft tissue .", "id": 548} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 54-year - old male patient with a height of 170 cm and weight of 77 kg visited a private hospital due to a headache and weakness in left muscle that started the day before his hospital visit . during the examination ,\nthe patient showed decreased consciousness , and internal hemorrhaging in the cerebral ventricle was observed in the ct scan , hence he was transferred to our hospital .\nwhen he arrived at the emergency room , the patient was semi - conscious and had difficulty in breathing , and his glassgow coma scale ( gcs ) showed severe head trauma with a total score of 8 or lower . the head ct scan revealed worsened stage of hemorrhage in the cerebral ventricle , so he was immediately intubated and transferred to the icu . a day after entering the icu ,\nthe hemorrhaging in the patient was still worsened according to the ct scan and he was in a semi - comatose state ; therefore , an extra ventricular drainage ( evd ) was done to decrease the pressure in the brain and hematoma aspiration was also carried out .\nin addition , an emergency tracheostomy was done at the same time since long term mechanical ventilation was expected .\npreoperative vitals were a blood pressure of 150/80 mmhg , a heart rate of 100/min , a respiration rate of 24/min , a body temperature of 38 , and a spo2 of 97% . after administering 0.2 mg of glycopyrrolate\nafter complete loss of consciousness , muscle relaxation was achieved with 8 mg of vecuronium .\nalfentanil at a concentration of 1.0 mg was administered to minimize hemodynamic changes when replacing the tube and at the same time anesthesia was maintained with o2 supply of 1 l / min , air supply of 2 l / min , and 2.0 vol% of sevoflurane . considering the difficulty in maintaining airway characteristics in head surgery , the previously intubated polyvinylchloride ( pvc ) plain tube was replaced with a reinforced tube .\nthe patient 's vitals immediately after intubation were blood pressure of 130/70 mmhg , a heart rate of 95/min , and a spo2 of 98% .\nstarting from the evd , the operation proceeded smoothly and the tracheostomy was done in 2 hours and 30 minutes .\nten minutes after starting the tracheostomy , the fio2 increased to 1.0 . while adjusting for bleeding around the tracheal cartilage with monopolar coagulation before inserting the tracheostomy tube , a fire of about 15 cm in size suddenly started perpendicular to the direction of the trachea .\nthe supply of sevoflurane and 100% o2 was immediately stopped after the initiation of fire and manual ventilation was done at a fio2 of 0.2 .\nnormal saline was used to extinguish the fire and soon the condition was brought under control .\nthe endotracheal tube ( reinforced tube ) was taken out , tracheostomy tube was intubated to maintain manual ventilation , and spo2 was again increased to 98% .\nvitals before and after the tracheostomy were stable except for the temporary decrease in spo2 .\nthe condition of the tube after extubation was as follows : the part directly above the cuff had holes due to melting from the heat ; the coil inside the tube had melted , and there was overall charring ( fig .\nthe operation was completed without occurrence of any further incident , and since the patient was still in a semi - coma state , he was transferred to the icu while maintaining bag ventilation through the tracheostomy tube . in the abga\nconducted directly after being transferred to the icu , the ph was 7.406 ; the pco2 was 33.6 mmhg ; the po2 was 121 mmhg ; the hco3 was 20.7 mmhg , and oxygen saturation was 97.8% .\nthere were no observable changes in the chest x - rays both , before and after the operation ( fig .\nthe patient showed no improvement in consciousness during continuous mechanical ventilation ; therefore , 5 days after the surgery , the patient was transferred to another hospital as per the wishes of the guardian .\nthere were no irregularities in the chest x - ray images and clinical symptoms after being monitored for 4 months post - surgery ( fig .\nintra - tracheal tube fire is rare and yet a critical emergency that can cause fatal complications . despite numerous studies on the cause and prevention of fire ,\nof course , when a fire occurs , the type of operation and the cause for the fire are different .\nit can occur during operations using lasers , in tracheostomies , and there exists reported incidents for double - lumen tubes .\nthe three important factors that contribute to the occurrence of intra - tracheal fires are oxygen , fuel , and heat .\nthe high concentration of oxygen is the main cause of fire , but there are reports of fires occurring at 50% oxygen concentrations and can even occur in 25% oxygen environments , which is similar to the atmosphere .\ntherefore , caution is needed especially in tracheostomy since 100% highly concentrated oxygen is typically used , which is characteristic of the operation . for fuel , the intra - tracheal tube itself is the problem since tubes generally consist of pvc material . in tracheostomy ,\nthe risk of fire is increased since fire - resistant tubes are not used , unlike in other laser operations .\nour present case also employed a reinforced tube , since tracheostomy was done after the neurosurgery , which is believed to be one of the reasons for the fire .\nthere are reports of heat occurring in all modes of cutting , coagulation , and blending .\ntherefore , when doing a tracheostomy , the use of electrocautery is minimized or a bipolar is used , but the bipolar can also cause sparks while coming into contact with tissue ; so it can not be considered as a completely safe alternative .\nour case also considered these points and tried to minimize the use of electrocautery during the operation .\nhowever , it is believed that the reinforced wire was exposed due to damage to the tube cover during the process of cutting into the mesh . there was immediate occurrence of hemorrhage before inserting the tube , and while urgently trying to control the bleeding , the electrocautery and reinforced wire are believed to have reacted to initiate the fire .\nalthough there are a number of reports on intra - tracheal tube fires and numerous reports on the review , prevention , and countermeasures of tube fires , currently there are no accurate protocols established regarding this situation . however , when similar cases and reports are put together , there are some common suggestions and advice , which can be organized as follows : 1 ) use a tube of sufficient length so the tip of the tube can reach directly above the carina to minimize the possibility of damaging the balloon during tracheostomy , 2 ) avoid using flammable gases for anesthesia , 3 ) fill the balloon with normal saline , 4 ) maintain the safest minimum level of fio2 when using nitrous oxide or helium , 5 ) remove the by - products of the electrocautery ( smoke , burnt tissue ) through a sufficient amount of suction before performing the tracheostomy , 6 ) insert the tube deeply before the tracheostomy , 7 ) the surrounding area needs to have sufficient hemostasis before proceeding and avoid using electrocautery for the tracheostomy , and 8) when there is hemorrhage after a tracheostomy , carry out ligature of the hemorrhage with the tube and cuff in place , or use bipolar electrocautery .\nthere are also reports , which state that peep ventilation can decrease the risk of fire . whereas , rhee et al . \nreported that by filling the balloon with normal saline and mucous lidocaine , tube fires can be prevented that can occur in laser operations as well as maintain the shape of the balloon and ventilation when there are punctures in the air balloon due to fire and other incidents .\nadditionally , maintaining the aridness of the operating room to prevent fires and preparing containers and ambu bags with normal saline in case of fire emergencies are also considered as important factors .\nthe above - mentioned methods may prevent fire emergencies , but necessary countermeasures to combat the occurrence of fire must also be devised\n. the anesthesiologist needs to first check the state of the patient , quickly separate the pipe streaming anesthetic gas from the tube , and attempt ventilation with atmospheric air . at the same time , there needs to be cooperation amongst the surgeons to extinguish the fire .\ndealing with a tube that has been on fire is another part that should not be ignored .\nthere is controversy regarding immediate extubation after the incidence of a tube fire . in the past ,\nimmediate extubation was recommended considering the chemical risks due to the evolution of toxic substances from the burnt tube and the damage to the trachea .\nhowever , chee and benumof argue that immediate extubation is not always the best option , considering that the damage from the fire is minimal in most of the cases of fire reported until now ; most of the patients undergoing tracheostomies have difficulties in maintaining their airways due to edema , which is the leading cause of morbidity and the increase in the death rate in accidents involving anesthesia is hypoventilation and hypoxia . in our case , immediate extubation and intubation of the endotracheal tube were done , but in post - operative examinations , there were no problems with the trachea itself and there was no chemical damage .\nit is most important to consider the risk benefit on a case - by - case basis rather than setting a general rule regarding the timing of the extubation . in conclusion , it is important in tracheostomies to understand that though occurrence of fires are rare , they are still possible along with other risk factors and the surgeons must be attentive in terms of preventing the occurrence of fires .\ncaution needs to be taken , since tube fires can occur in unexpected areas such as the reinforced wire in our case . in addition\n, when a tube fire does occur , it is very important to minimize additional damage or burns in the respiratory tract through appropriate and fast responses , and to determine a suitable time for extubation according to the specific situation .", "answer": "every operation could have a fire emergency , especially in the case of a tracheostomy . \n when a flammable gas meets a source of heat , the danger of fire is remarkable . \n a tracheal tube filled with a high concentration of oxygen is also a great risk factor for fire . \n intra - tracheal tube fire is a rare , yet critical emergency with catastrophic consequences . \n thus , numerous precautions are taken during a tracheostomy like , use of a special tube to prevent laser damage , ballooning of the tube with normal saline instead of air , and dilution of fio2 with helium or nitrogen . since the first recorded cases on tube fires , most of the fires were initiated in the balloon and the tip . in the present case report \n , however , we came across a fire incidence , which originated from the wire .", "id": 549} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nonchocerciasis is the second leading infectious cause of blindness in the world , after trachoma . for centuries\nblack fly , the disease is prevalent in 19 african countries , and endemic in now just six american foci . in total ,\n37 million people are thought to have active disease , with nearly all such cases in africa where over 100 million people live at risk of new infection .\nthis old world disease originated in africa and spread to new world via the slave trade , where it formerly existed in 13 discrete geographic foci within latin america . over 500,000 individuals live with a significant visual impairment from the disease , with an additional 270,000 individuals who have suffered from complete vision loss .\nthe simulian vector is infected when biting infected humans , and after maturation of larva within the fly , can then re - infect others during subsequent blood - meals .\nthese flies breed within and live around fast - flowing rivers ( hence the name river - blindness ) , and generally only persons living in and around these areas are at risk for infection after repeated biting\n. transmission efficiency of most simulian species is quite low relative to other diseases ( e.g. , anopheles mosquito with malaria ) , although variable between regions , such that travelers are generally not at risk for this infection unless living long - term in endemic areas .\nonce deposited within the skin , infective stage larvas maturate and trigger the development of fibrous subcutaneous nodule in which they will mate and reproduce .\nannually , female adult worms can release hundreds of thousands of microfilariae ( mf ) that migrate freely through skin with the potential for reaching and invading the eye . in the skin , mf cause pruritis and dermatitis , and eventually can lead to skin atrophy and discoloration ( leopard skin ) . in the eye\nthe ocular pathology of this disease occurs in both anterior and posterior segments of the eye .\nanteriorly , mf travel through scleral and subconjunctival tissues to reach the cornea whereby they attempt to penetrate and migrate through the cornea . within the corneal stroma ,\nbacteria , an intracellular , rickettsia - like bacteria that lives symbiotically with mf and adult onchocerca worms .\ninterestingly , these organisms are extremely important to the lifecycle and reproduction of onchocerca , and without them , female adult worms can not reproduce . within the cornea , as with other tissues , release of wolbachia elicits an immune response and inflammation .\nthis process clinically appears in the cornea as a punctate keratitis ( pk ) , lesions that gradually resolve over 23 months as the mf are degraded by immune cells .\nthe prevalence of pk has served as the cornerstone for evaluating the progress of mass ivermectin therapy during recent elimination campaigns in the americas .\nrepeated mf - associated corneal insults eventually lead to sclerosing keratitis ( opacification and scarring of the cornea ) , a major cause of onchocercal - related visual loss . a large proportion of visual morbidity and blindness caused by this disease , however , is due to posterior pole lesions that persist even after ivermectin therapy.[1416 ] in the posterior segment of the eye , mf invade retinal tissues causing chronic chorioretinitis , inflammation , scarring , and in some cases optic atrophy and glaucoma .\nit is likely that dying mf in these tissues trigger an inflammatory response there , one that is potentially promoted by cross reactivity between o. volvulus antigen ( ov39 ) and human retinal pathogen ( hr44 ) found in the optic nerve and neural epithelial layers of the retina.[1719 ] interestingly , onchocercal chorioretinitis continues despite ivermectin therapy and extermination of the parasite from the eye , potentially as a result of an autoimmune response provoked by the parasite .\ndiagnosing onchocerciasis relies on demonstration of characteristic eye pathology ( visible mf in the cornea or anterior chamber ) or demonstration of mf within the skin . on the individual level , visible mf in the anterior segment\nare specific to onchocerciasis ; however , it is often difficult to observe mf in the anterior chamber , and punctuate keratitis lesions are fleeting and can be nonspecific for onchocerciasis if the degraded mf is not visible within the lesion . at lower levels of microfiladermia ,\nskin - snips , a superficial ( dermal ) biopsy of 13 mg , examined microscopically for mf are invasive and suffer from poor sensitivity in patients with low levels of microfiladermia .\npcr examination of skin snips improves this situation , although sensitivity is still low in such persons , making this tool less useful in endemic areas where ivermectin has been used to treat this disease for years .\nskin patch testing with diethylcarbamazine ( dec ) has been shown as a good alternative to skin snip evaluations in africa .\nthis test relies upon dec killing of mf within the dermis and subsequent provocation of a hypersensitivity reaction ( i.e. , localized mazzoti reaction ) .\nadvantages over skin snip evaluation ( noninvasive , better patient acceptance ) , although can be operationally difficult ( patches can fall off , patients must return in 24 h for test reading ) . the sensitivity and specificity of the dec patch test\nis not yet clear , although recent studies using newer formulations suggest its utility in monitoring for infection within mass onchocerciasis treatment programs in africa .\nserologic antibody tests using recombinant antigens , such as the ov-16 , can be useful , but can not distinguish between past and active infection.[2629 ] in addition , the sensitivity of this assay is questionable , with at least one study showing that a large percentage of those with active eye disease living in endemic areas have negative ov-16 results .\na highly specific antigen detection test capable of diagnosing active infection has been reported in the literature , but to date , has received little evaluation .\nthe development of a highly specific and sensitive test capable of determining active onchocercal infection remains an imperative for public health campaigns seeking to control and eliminate this parasite .\nthe development of a safe and effective macrofilaricidal drug has been long sought for this disease . for years ,\nivermectin , a macrocyclic lactone , has been the mainstay of therapy ; however , ivermectin kills only the mf . in effect\n, ivermectin serves as a birth control device for adult worms , in that female worms are temporarily sterilized for an average of 6 months , preventing the release of mf during that time .\nconsequently , periodic single dose oral treatment prevents the onset of new ocular and dermal lesions and reduces transmission as the vector is less exposed to mf during its feeding on human skin .\nocular barrier , thus avoiding intraocular killing of mf and subsequent intraocular damage due to inflammation .\nhowever , new therapies targeting the endosymbiotic wolbachia within the adult worms have now been proven to be effective in causing long - term ( and potentially permanent ) sterilization of adult worms and early worm death .\ndoxycycline treatment ( 100mg / day ) for 6 weeks with a single dose of ivermectin has become the treatment of choice for individuals based on recent clinical trial data , although 4 week courses of doxycycline or rifampin are also effective [ table 1 ] . from a public health perspective , however , the mass treatment of affected populations with doxycycline is difficult given the length of necessary therapy and the potential for re - infection in endemic areas .\nhowever , these therapies may be of particular use in areas of co - endemicity with loiasis where mass distribution of ivermectin is complicated by potential adverse events in patients co - infected with loiasis . studies evaluating the efficacy of antibiotic therapy directed at onchocercal endosymbiotic wolbachia bacteria\nthe development of a safe and effective macrofilaricidal drug has been long sought for this disease . for years ,\nivermectin , a macrocyclic lactone , has been the mainstay of therapy ; however , ivermectin kills only the mf . in effect\n, ivermectin serves as a birth control device for adult worms , in that female worms are temporarily sterilized for an average of 6 months , preventing the release of mf during that time .\nconsequently , periodic single dose oral treatment prevents the onset of new ocular and dermal lesions and reduces transmission as the vector is less exposed to mf during its feeding on human skin .\nocular barrier , thus avoiding intraocular killing of mf and subsequent intraocular damage due to inflammation .\nhowever , new therapies targeting the endosymbiotic wolbachia within the adult worms have now been proven to be effective in causing long - term ( and potentially permanent ) sterilization of adult worms and early worm death .\ndoxycycline treatment ( 100mg / day ) for 6 weeks with a single dose of ivermectin has become the treatment of choice for individuals based on recent clinical trial data , although 4 week courses of doxycycline or rifampin are also effective [ table 1 ] . from a public health perspective , however , the mass treatment of affected populations with doxycycline is difficult given the length of necessary therapy and the potential for re - infection in endemic areas .\nhowever , these therapies may be of particular use in areas of co - endemicity with loiasis where mass distribution of ivermectin is complicated by potential adverse events in patients co - infected with loiasis .\ntwo large public health campaigns currently operate worldwide with goals of either elimination or control of this parasite .\nthe cornerstone of these campaigns is the mass distribution of ivermectin , delivered semi - annually or annually , and donated in perpetuity for this cause by merck .\nwhen ivermectin is delivered as such in the long - term , sustained fashion to large percentages of at risk populations ( e.g. , > 85% is the goal in latin america ) , dermal mf levels fall such that new eye lesions and transmission are prevented .\nthe african programme for onchocerciasis control ( apoc ) currently strives to eliminate onchocerciasis as a \npublic health concern by delivering ivermectin to populations where dermal mf prevalence of 40% .\nrecent studies in mali and senegal indicate a tremendous reduction in microfilaridermia and a profound reduction in the prevalence of black fly infection indicating that elimination is feasible in at least some african foci . in the americas ,\nthe onchocerciasis elimination program for the americas ( oepa ) strives to completely eliminate the disease by treating 85% of at risk persons with ivermectin every 6 months . as of 2010 ,\n7 of the 13 endemic foci have been declared free of onchocerciasis , treatment with ivermectin therapy has stopped , and surveillance for disease recrudescence will continue for 3 years prior to a declaration of disease elimination in these foci .\ncurrently , active eye disease only exists within several foci within venezuela and brazil , where treatment coverage has been more recently increased and it is anticipated that elimination of eye disease in these areas will follow in subsequent years .\nas anti - wolbachia therapy has been shown to be effective in clinical trials , its optimal use within these public health campaigns is not yet clear . within latin america ,\nconceivably , anti - wolbachia therapy could be used in limited circumstances either to mop - up or \ncatch - up in regions that continue to have active disease or where ivermectin coverage has been less than complete . as elimination with ivermectin looms near in latin america , however , it is not clear that such alternative therapies will ever be needed .\nwithin africa , at least one large scale community directed treatment program using doxycycline has been reported . as with latin america , a role for mass doxycycline therapy there has not yet been clearly defined , and might differ by region based on vector competence , parasite pathogenicity , public health capacity , and the ability to deliver 46 weeks of such therapy in mass fashion .\nlastly , anti - wolbachia would theoretically become very important in either region should the parasite develop resistance to ivermectin . although ivermectin resistance has not definitively been reported , it remains a concern and anti - wolbachia therapy offers an alternative should such an event occur .\nin latin america , oepa has declared the year 2015 as a goal for the final year of mass treatment with ivermectin for onchocerciasis , and in africa great reductions in disease have been documented with mass ivermectin therapy . although current progress with these mass ivermectin drug campaigns is encouraging , improved diagnostics and further development and evaluation of anti - wolbachia and other drug therapies will improve the chances that these large regional public health initiatives will achieve long - term success .", "answer": "for decades , onchocerciasis ( or river blindness ) was one of the most common infectious causes of blindness in the world . \n primarily an infection of africa , with limited distribution in the new world , disease due to the nematode onchocerca volvulus is rapidly diminishing as a result of large public health campaigns targeting at risk populations in africa and the americas . existing and newly - developed treatment strategies \n offer the chance to eliminate onchocercal ocular morbidity in some parts of the world . \n this article reviews these treatment strategies , current clinical and epidemiologic aspects of onchocerciasis , and the next steps toward elimination .", "id": 550} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npercutaneous nephrolithotomy ( pcnl ) is a widely accepted treatment for urinary calculi > 2 cm or resistant to other modalities .\ncomplications of this procedure are well reported ; however , to our knowledge no mention has occurred in the literature of a retained nephrostomy tube after pcnl .\nthus , we will present the management of a retained council tip catheter after pcnl .\na 76-year - old gentleman underwent a pcnl for a 2.2x1.4-cm lower pole calculus via an uneventful upper pole puncture .\nincomplete stone fragmentation was obtained using the ultrasonic lithotripter ; therefore , a 24-french council tip nephrostomy tube was placed , the balloon was inflated with 3 ml of sterile water , and the patient was scheduled for a second look nephroscopy when a holmium laser was available .\none week later at the second look nephroscopy , attempts to deflate the catheter balloon were unsuccessful .\nafter transection of the balloon port valve , attempted passage of a 0.038 movable core bentson guidewire down the balloon port was unsuccessful .\nan antegrade nephrostogram outlined the catheter balloon within the renal pelvis ( figure 1 ) . with the c - arm in a vertical orientation ,\nan 18-gauge chiba needle ( cook , bloomington in ) was advanced through a puncture site directly over the balloon under fluoroscopic guidance .\nthe balloon was successfully punctured by the chiba needle with clear efflux through the needle .\ncontrast was then instilled through the chiba needle to evaluate the integrity of the balloon and exclude the possibility of retained balloon fragments from a ruptured balloon ( figure 2b ) .\nflexible nephroscopy was performed to evaluate for balloon fragments , which were not identified , and to remove the lower pole stone .\n( a ) chiba needle ( white arrow ) has punctured and drained the catheter balloon .\n( b ) contrast injected via chiba needle has filled the catheter balloon ( dark arrow ) and confirmed its integrity .\na retained urethral catheter due to balloon malfunction is a well - recognized urologic complication .\nmany solutions to this problem have been attempted , including overinflation until rupture , puncture of the balloon via a wire through the balloon port , and puncture of the balloon under ultrasound guidance via a suprapubic or transvaginal route . given this infrequent but known complication of balloon - type cystostomy catheters , it is not surprising that a similar complication occurred in our patient .\nour familiarity with the use of the chiba needle and 3-dimensional fluoroscopy for percutaneous renal access facilitated percutaneous puncture of the catheter balloon .\nif equipment or experience limits the urologist 's ability to perform this technique , collaboration with an interventional radiologist using conventional c - arm or ultrasound for guidance should be considered .\nprevention of a retained catheter due to a balloon - port malfunction requires use of sterile water instead of saline and limiting the time of catheter placement .\nmalecot tubes have been utilized for nephrostomy drainage , but these tubes are not without difficulties . tissue bridge formation over flanges of the tube has occurred , requiring endoscopic removal .\ntubeless pcnl would avoid these issues entirely ; however , the tubeless technique is contraindicated in the face of significant postoperative bleeding , urinary extravasation , ureteral obstruction , or anticipated need for a second - look nephroscopy .\npigtail catheters following pcnl may represent a good alternative for drainage and access , while minimizing the risk of catheter malfunction or retention .", "answer": "percutaneous nephrolithotomy is a widely accepted treatment for urinary calculi , but it is not without complications . we present the case of a 76-year - old male with a retained council tip catheter after percutaneous nephrolithotomy . \n fluoroscopic guidance was used to perform percutaneous puncture of the catheter balloon , and the catheter was removed without complication . \n advantages of various nephrostomy tube designs and additional measures to prevent this type of complication are discussed .", "id": 551} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n lipoma is a rare tumor but can be found at various sites in the abdominal cavity ( fig .\n2 ) . if it is of a large size , it can compress adjacent tissues or organs and become heterogeneous . in such cases ,\nimaging is incapable of distinguishing it from liposarcoma.lipoblastoma is a type of a benign tumor with embryonic fat .\nit is usually found in the extremities and torso whereas abdominal cavity belongs to its rather rare sites . in us , such tumors are echogenic .\nlipoblastomatosis is a form of this tumor characterized by aggressive localized growth.hibernoma is a benign tumor , mainly composed of brown fat , in whose cells the numbers of mitochondria responsible for enhanced metabolic activity are impressive .\nthese tumors are rarely encountered in the retroperitoneal space but are also echogenic with well - or ill - defined margins .\ntheir characteristic feature is evident flow in color doppler.other benign tumors with a fat component , such as myolipoma , angiomyolipoma and myelolipoma , apart from teratoma ( which is usually benign ) , tend to be homogeneous with echogenicity increased to various degrees ( fig . 3 , 4 ) .\nonly gonadal germ cell tumors , such as teratoma and dermoid cyst that arise from several germ layers , frequently have irregular echotexture due to the presence of fluid sebum , hair , soft tissues and bony elements .\nthat is why they are encountered in solid , cystic or solid - cystic forms ( fig .\nmature fat tissue can also be found in choristoma which , however , is not a neoplasm .\nlipoma is a rare tumor but can be found at various sites in the abdominal cavity ( fig .\n2 ) . if it is of a large size , it can compress adjacent tissues or organs and become heterogeneous .\nit is usually found in the extremities and torso whereas abdominal cavity belongs to its rather rare sites . in us , such tumors are echogenic .\nhibernoma is a benign tumor , mainly composed of brown fat , in whose cells the numbers of mitochondria responsible for enhanced metabolic activity are impressive .\nthese tumors are rarely encountered in the retroperitoneal space but are also echogenic with well - or ill - defined margins .\nother benign tumors with a fat component , such as myolipoma , angiomyolipoma and myelolipoma , apart from teratoma ( which is usually benign ) , tend to be homogeneous with echogenicity increased to various degrees ( fig . 3 , 4 ) .\nonly gonadal germ cell tumors , such as teratoma and dermoid cyst that arise from several germ layers , frequently have irregular echotexture due to the presence of fluid sebum , hair , soft tissues and bony elements .\nthat is why they are encountered in solid , cystic or solid - cystic forms ( fig .\nmature fat tissue can also be found in choristoma which , however , is not a neoplasm .\ntwo views show lipoma ( arrows ) as a slightly echogenic lesion in the supraperitoneal fat three lipomas ( l ) in the small bowel mesentery , which in computed tomography showed density ranging from 57 to 74 hounsfield units two views show angiomyolipoma ( l ) located entirely in the adipose capsule of the right kidney .\nan arrow points to the site of regrowth in the form of the beak sign myelolipoma in the right suprarenal field ( arrow ) as a visible hyperechoic mass a heterogeneous mass arising from the retroperitoneal space is a mature teratoma with slight calcifications ( arrows )\nliposarcoma is the only malignancy deriving from adipose tissue that is relatively frequently encountered in the retroperitoneal space ( it constitutes nearly 1/3 of sarcomas at this site and 1015% of all neoplasms of this type ) . according to the who , these tumors can be divided into five histological subtypes depending on the grade of their differentiation ( well - differentiated , dedifferentiated , myxoid , round cell , pleomorphic ) , which is relevant in prognosis .\nits presence can be indicated only by uneven margins and heterogeneous enhancement upon contrast agent administration .\npoorly differentiated subtypes account for even 40% of local relapses , and metastases are observed in 17% of cases . as has already been mentioned , well - differentiated liposarcoma is difficult to distinguish from lipoma also in sonography .\none of the differential criteria can be tumor 's reaction to compression with a transducer ( fig .\nmore aggressive forms of this tumor , however , tend to be unevenly delineated , present heterogeneous echotexture and infiltrate adjacent tissues ( fig .\nmyxoid liposarcoma is characterized by a cystic structure and should be distinguished e.g. from lymphangioma , teratoma or cystic mesothelioma .\nno lesion compressibility when pressure is applied with the transducer ( arrow ) heterogeneous retroperitoneal liposarcoma infiltrates into adjacent tissues ( arrows ) mesenteric liposarcoma with pathological vascularity finally , immature teratoma must be mentioned .\nit is a primary germinal tumor that can contain adipose tissue and occurs at similar sites .\nthey are characterized by the predominance of a solid component , and the only sign suggesting a malignancy is poorly circumscribed margins . a chance for malignant transformation\ncystic lesions can correspond to mesenteric cysts , lymphatic or vascular angiomatosis and even a cystic form of peritoneal mesothelioma , which is considered a benign lesion ( fig .\nthe differential diagnosis of these pathologies should include ovarian cystic tumors , endometrial cysts and cystic tumors growing beyond organs , e.g. of the pancreas , kidneys or liver .\nsolid tumors found at these sites include : leiomyoma and rhabdomyoma , angiomas as well as stromal , neurogenic and desmoid tumors ( fig .\ndesmoid tumors , also called fibromatosis , are an interesting group of benign tumors that exhibit local aggressiveness and have considerable tendency to recur ( in approximately 50% of cases ) .\nall lesions were hypoechoic with slightly irregular echo patterns , 59% of cases were well - defined and 41% had irregular margins .\nthe differential diagnosis should include sarcomas , mainly the two types that are most frequently found in soft tissues : histiocytic fibrosarcoma and liposarcoma , i.e. lesions characterized by higher echogenicity .\nit is of note that desmoid tumors frequently coexist with familial adenomatous polyposis , which is estimated at 918% of cases . of all imaging modalities ,\nsome authors recommend punch or even surgical biopsy in the event of doubts . in this case ,\nmesenteric lymphangioma as a multilocular lesion without flow ( arrow ) retroperitoneal neuroblastoma in a 13-year - old ( arrows ) .\naorta , v inferior vena cava desmoid , poorly vascularized tumor ( d ) in the small bowel mesentery\nthese changes are rarely encountered but they represent a rich spectrum of mainly mesenchymal neoplasms : fibrosarcoma , malignant fibrous histiocytoma , hemangiopericytoma , leiomyosarcoma , rhabdomyosarcoma and gastrointestinal stromal tumors ( fig .\nan epithelioid malignant neoplasm encountered at this site is malignant peritoneal mesothelioma , a lesion that almost exclusively develops in males in the fifth and sixth decade of life .\nit can assume two morphological forms : irregular peritoneal infiltration without ascites ( dry appearance ) ( fig .\n13 ) and nodular thickening of the peritoneum and greater omentum with ascites ( wet appearance ) .\nlesions of this type must be distinguished from papillary serous carcinoma of the peritoneum ( a rare neoplasm found in elderly women ) , abdominal carcinomatosis , in which ascites prevails over implants , and peritoneal tuberculosis , in which there are no tumorous lesions ( but ascites is present , the greater omentum is thickened with preserved smooth surface and the mesenteric lymph nodes are enlarged ) .\nlymphomas , however , are characterized by considerable abdominal lymphadenopathy , rare and slight ascites and no omental involvement .\nrhabdomyosarcoma with rich vascularity in the retroperitoneal space ( arrows ) two views present poorly vascularized malignant mesothelioma of the greater omentum ( m )\nthis is the most numerous group with prevailing carcinoma foci , mainly deriving from abdominal organs , such as pancreas , stomach , large bowel or ovaries .\nthese lesions spread by direct extension , via the lymphatic system or blood stream and through the peritoneal cavity . their echotexture can vary .\n14 ) and thickened parietal peritoneum ( its normal thickness is up to 1.5 mm ) ( fig .\nechogenic lesions that only slightly differ from the surrounding tissues are the hardest to find ( fig .\nperitoneal sites at which carcinoma implants tend to develop are : the recto - uterine pouch , right iliac fossa , right paracolic gutter and the region of the upper sigmoid mesentery .\nmoreover , ovarian carcinoma cells frequently migrate to the supra- and subhepatic area ( fig .\nwell - designed prospective studies have proven ultrasound imaging to be highly useful in detecting abdominal carcinomatosis .\nit occurred that lesions in the greater omentum were the easiest to detect ( 91% ) whereas those in the small bowel mesentery were the hardest to find ( 67% ) .\nmoreover , ultrasound guidance enables one to obtain diagnostically valuable material for cytological and histological analysis in the vast majority of such cases .\nmetastasis of malignant melanoma ( m ) from the interscapular space to the small bowel mesentery peritoneal carcinomatosis of ovarian carcinoma . thickened hypoechoic parietal peritoneum with signs of vascular flow ( arrows ) two views show a hyperechoic implant of ovarian carcinoma in the gastrocolonic ligament ( arrows ) ovarian carcinoma implants in the pouch of morison ( arrows ) another rare neoplasm encountered in fatty bodies of the abdominal cavity is non - hodgkin lymphoma .\nthe involvement of the small bowel mesentery , with prominent , large mesenteric lymph nodes , is observed to occur in a half of patients with this neoplasm .\nthese lymph nodes , together with the superior mesenteric vessels , create a so - called sandwich image ( fig .\nit is usually a small neuroendocrine neoplasm located in the small bowel . sometimes , the first morphological sign of its existence is the presence of mesenteric abnormalities in the form of enlarged lymph nodes or a hypoechoic mass .\nmesenteric thickening or contraction , which can lead to small bowel obstruction , is more rarely a predominant element of the image . any doubts in the assessment of these lesions require verification in computed tomography and , sometimes , magnetic resonance imaging . ultrasound imaging , however , enables precise , percutaneous sampling for cytological and histological analysis , which is worth remembering and applying . \nsandwich sign in the small bowel mesentery ( arrows ) created by enlarged lymph nodes surrounding the superior mesenteric vessels a manifestation of non - hodgkin lymphoma extranodal location of follicular lymphoma in the small bowel mesentery ( arrow ) lesions in the lymph nodes , which are relatively frequently affected by various neoplastic and non - neoplastic processes , have been presented only briefly since these issues are too broad to be included in this review .\nauthors do not report any financial or personal connections with other persons or organizations , which might negatively affect the contents of this publication and/or claim authorship rights to this publication .", "answer": "this article focuses on various cancerous lesions that are found beyond organs in the intra - abdominal fat and can be visualized with ultrasonography . \n these lesions are divided into five groups . \n the first group includes primary benign tumors containing adipocytes , such as lipoma , lipoblastoma , hibernoma and other lesions with an adipose tissue component , such as myolipoma , angiomyolipoma , myelolipoma and teratoma . \n the second group comprises primary malignant adipocytecontaining tumors , including liposarcoma and immature teratoma . \n the third group contains primary benign tumors without an adipocyte component that are located in intra - abdominal fat . \n this is a numerous group of lesions represented by cystic and solid tumors . \n the fourth group encompasses primary malignant tumors without an adipocyte component that are located in intra - abdominal fat . \n these are rare lesions associated mainly with sarcomas : fibrosarcoma , malignant fibrous histiocytoma , hemangiopericytoma and leiomyosarcoma . \n an epithelioid tumor at this site is mesothelioma . \n the last but not least group includes secondary malignant tumors without an adipocyte component located in intra - abdominal fat . \n this is the most numerous group with prevailing carcinoma foci . for each of these groups , \n the authors present ultrasound features of individual lesions and discuss their differential diagnosis . in the vast majority of cases , \n the material for cytological and histological analysis can be obtained during ultrasound - guided procedures . \n this is the advantage of this imaging modality .", "id": 552} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe leucine - rich , glioma inactivated 1 ( lgi1 ) gene was identified at the brake point of a reciprocal chromosome translocation t(10;19)(q24;q13 ) in the glioblastoma cell line t98 g .\nlgi1 protein includes domains presumably involved in protein - protein interaction such as the leucine - rich repeats flanked by cysteine rich regions and the seven - bladed beta - propeller domain [ 24 ] .\nlgi1 gene is predominantly expressed in brain , and it is associated with autosomal dominant lateral temporal epilepsy ( adlte ) [ 5 , 6 ] . although the specific function of lgi1 remains to be defined , it was suggested to form complexes with kv1.1 potassium channels , essential regulators of synaptic transmission in brain and also to be a ligand of the trans - membrane receptor adam22 , a protein highly expressed in brain whose function is still uncertain [ 7 , 8 ] .\nthe loss of lgi1 expression in most high - grade gliomas supported the function of tumor suppressor gene . in agreement with this hypothesis the reexpression of lgi1 in glioma cells , lacking endogenous lgi1 , impaired cell growth and migration capacity .\nthese phenotypic changes were linked with the downregulation of matrix metalloproteinase ( mmp ) genes by lgi1-mediated inhibition of the erk / mapk pathway . a role of lgi1 in the development of malignant brain tumors\nwas substantiated by the discovery of somatic missense mutations in lgi1 gene associated with high- and low - grade gliomas .\nthe ability of lgi1 to suppressor growth of neuroblastoma cells was suggested by the results of lgi1 overexpression , which was shown to impair proliferation and to induce apoptosis through the inhibition of the pi3k / akt pathway [ 12 , 13 ] .\nfurther support to the tumor suppressor function of lgi1 was provided by a comprehensive study on malignant esophageal tumors ( barrett's - related adenocarcinomas ) showing that expression of lgi1 was consistently downregulated .\nthe aim of this study was to establish whether lgi1 was capable to suppress growth of cancer cells different from glioblastoma and neuroblastoma .\nfor this purpose we performed stable expression of lgi1 in hela cell , which is derived from a human cervical adenocarcinoma and expresses the human papillomavirus proteins e6/e7 ( hpv-18 ) .\nessentially these viral proteins sustain cell proliferation and survival through the inactivation of tumor suppressors p53 and prb , which are implicated in cell cycle arrest and induction of apoptosis [ 16 , 17 ] . for these features conferring remarkably vigorous growth\nthe results showed that expression of lgi1 inhibited the rate of hela cell proliferation and increased cellular death .\nfurthermore lgi1 altered expression of key regulators of apoptosis such as the antiapoptotic b - cell lymphoma 2 gene ( bcl2 ) and of the proapoptotic b - cell lymphoma 2-associated x protein gene ( bax ) .\nthe lethal effect produced by lgi1 expression in hela cells suggests that the proposed role of tumor suppressor might be extended to adenocarcinoma - derived cells .\nhela cells ( atcc number : ccl-2 ) were cultured in dulbecco 's modified eagle medium ( dmem , low glucose ) with 10% heat inactivated fetal calf serum ( fcs ) . for transfection cells ( 1.5 10 )\ntransfection with plasmid pclgi1 including the human lgi1 cdna ( 2075 bp ) or with empty vector pcdna3 ( 10 g / ml each ; invitrogen , groningen , the netherlands ) was performed by the dna ca - phosphate coprecipitation .\ncells were cultured for 48 hours after transfection ; then they were replated at low density .\ntotal rna was isolated from subconfluent cells by the geneelute mammalian total rna kit ( sigma chemical co. , st louis , mo , usa ) .\nthe cdna synthesis was performed by the reverse transcriptase improm - ii starting from random primer examer ( promega , madison , wi usa ) .\nfor quantification of lgi1 mrna , a cdna segment of ( 236 bp ) was amplified with primers : 5-tgtaaactgaaatggctagtggaa , and 5-agtaaaaggctgagcgatgactac . \namplification of a bcl2 segment ( 258 bp ) was carried out with primers : 5-ggtcatgtgtgtggagagcgt , and 5-acttcacttgtggctcagataggc . a bax fragment ( 539 bp )\na portion of the glyceraldehyde-3-phosphate dehydrogenase ( gapdh , 909 bp ) was amplified using primers : 5-gaccccttcattgacctcaactaca and 5-ggtcttactccttggaggccatgt ( clontech , palo alto , ca usa ) . for the semiquantitative rt - pcr analysis\ndifferent number of pcr cycles ( < 25 ) and serial cdna dilutions were employed to establish conditions of linear amplification .\nthe pcr products were separated by agarose gel electrophoresis ; then the net intensity of ethidium bromide stained bands was determined using the kodak 1 d image analysis software .\nthe following antibodies ( santa cruz biotechnology , santa cruz , ca usa ) were used to probe blots : antibody c-19 directed to the c - terminal peptide of lgi1 ( 60 kda ) , affinity purified polyclonal antibody ( bax 21 ) against bax protein ( 23 kda ) , and monoclonal antibodies to bcl-2 and gapdh proteins ( 28 kda and 36 kda , respectively . the immunoreactions were revealed by the ecl reagent ( pharmacia amersham biotech , little chalfont , uk ) and quantified by the kodak 1 d image analysis software by evaluating the net intensity of the bands . an elisa immunoassay based on brdu incorporation was employed to measure cell proliferation according to the instruction procedures ( roches diagnostic , germany ) .\ncells were plated in quadruplicate on 96 well cluster plates ( 100 cells / mm ) and cultured for 24 hours .\nabsorbance at ( 450690 nm ) was measured using a plate reader . to determine the fraction of dead cells , the lactate dehydrogenase ( ldh ) released in the medium and that present in intact cells was measured using the cytotox non - radioactive cytotoxicity assay ( promega , madison , wi usa ) .\ncells were plated on 96-well plates ( 100 cells / mm ) and cultured for 24 hours .\none half of the culture medium was transferred to a fresh well to determine ldh spontaneously released by dead cells .\nthen the conversion of tetrazolium salt ( int ) into the red formazan product by ldh activity was measured ( absorbance 490 nm ) .\nthe fraction of dead cells was calculated as follows : % cytotoxicity = [ spontaneously released ldh 2 100]/total ldh . the apo - one homogeneous caspase-3/7 assay ( promega )\ncells were seeded on 96-well plates ( 100 cells / mm ) , and the caspase-3/7 substrate z - devd - r110 was added 24 hours later .\nthe reaction was carried on for 6 hours , and the measurement of fluorescence was then performed by a plate spectrofluorimeter ( 485 nm excitation wavelength , 530 nm emission wavelength ) .\nldh assays were performed on replicated cell samples to determine the number of living cells , which was used to normalize caspase activity .\nexperimental data were expressed as the mean sd . to determine the significance of variations , values were analyzed by student 's t - test ; levels of p < .05 were considered to be significant .\nstable transfection of hela cells with lgi1 cdna was performed to establish whether expression of lgi1 might affect cell viability .\nthe level of lgi1 expression was evaluated in three cell clones designated he - lgi1 - 1 , he - lgi1 - 2 , and he - lgi1 - 3 , respectively ( figure 1 ) .\nthe results of the quantification of lgi1 mrna was quite in agreement with the estimated values of lgi1 protein ( table 1 ) .\nalthough lgi1 protein was detected in whole cells sample , the possibility that it might be secreted as it occurred in 293 t cells can not be excluded , since it might be bound to the cell surface .\nthe endogenous expression of lgi1 in nontransfected hela cells and in cell clones stably transfected with empty vector was undetectable by rt - pcr and western blotting ( see he - pcdna3 ; figure 1 and table 1 ) .\nthe absence of lgi1 expression in human uterine tumors and in normal uterine tissue is supported by the analysis of expressed sequence tags ( ests ) reported by unigene and is in agreement with lack of lgi1 expression in mouse uterus .\nthe brdu incorporation procedure was employed to evaluate the influence of lgi1 expression on the rate of hela cell proliferation .\nall cell clones expressing lgi1 exhibited a lower proliferation rate in comparison with control cells transfected with empty vector ( figure 2 ) , which were similar to nontransfected hela cells ( not shown ) .\nwith he - lgi1 - 1 cell clone , in which lgi1 expression is very little , decrease of cell proliferation was on average 30% . with he - lgi1 - 2 cells , expressing the highest lgi1 levels the decrease was 80% , whereas it was 70% with helgi1 - 3 cells , showing intermediate levels of lgi1 expression ( figure 2 ) .\nthe results showed that the inhibitory effect of lgi1 on cell proliferation was proportional with the levels of lgi1 expression . to establish whether expression of lgi1 also might affect survival of hela cells we measured the amount of ldh spontaneously released in the medium as a consequence of cell death .\nthe fraction of dead cells was significantly greater in cell clones expressing lgi1 in comparison with control cells ( figure 3 ) .\nin particular , the percentage of he - lgi1 - 1 dead cells was on average 7% , slightly but significantly greater than that of he - pcdna3 cells , which was 5% .\nthe lethal effect was much greater with he - lgi1 - 2 and he - lgi1 - 3 , whose fractions of dead cells were on average 26% and 21% , respectively .\nthe decline of cell survival was clearly correlated with the levels of lgi1 expression , likewise inhibition of cell proliferation . since\nsignificant effects were obtained with cell clone helgi1 - 1 expressing very low levels of lgi1 , it can be suggested that the impairment of cell proliferation and survival was a consequence of the proper lgi1 activity rather than the outcome of artificial overexpression .\nfurthermore , these effects on cells of epithelial origin exclude the requirement of interactions with proteins specifically expressed in brain for the ability of lgi1 to contrast cell growth and survival . to gain information on the process of hela cell death caused by the expression of lgi1 we measured the activity of the apoptosis effectors caspase-3 and -7 in the experimental conditions employed to monitor cell death ( figure 4 ) .\nthe relative fluorescence emitted by the specific caspase-3/7 substrate upon cleavage was particularly enhanced with he - lgi1 - 2 ( 7.4-fold ) and he - lgi-3 cells ( 4.2-fold ) , whereas a modest increase was measured with he - lgi1 - 1 ( figure 3 ) .\nthe results supported the possibility that expression of lgi1 might trigger apoptosis of hela cells . to substantiate the induction of apoptosis of hela cell expressing lgi1 we measured the level of the antiapoptotic bcl2 and of the proapoptotic bax gene expression , since the relative proportion of these proteins plays a central role in the control of cell survival .\na significant decrease of bcl2 mrna and protein was measured in cell clones expressing lgi1 in comparison with control cells , whereas the expression of bax was consistently increased ( figure 1 ; table 1 ) . in particular , the upregulation of bax expression was proportional with the levels of lgi1 , with a maximum increase of 4.6-fold of bax protein in he - lgi1 - 2 ( table 1 ) .\nthe results showed that the antiapoptotic bcl2 gene was downregulated and that of its opponent proapoptotic bax was upregulated as a consequence of lgi1 expression .\na decreased ratio of bcl2/bax favors the release of apoptogenic molecules from mitochondria , which activate the intrinsic pathway of apoptosis in various cancer cells , including hela [ 2126 ] .\nthus lgi1 might increase the susceptibility of hela cells to spontaneous apoptosis , similarly to what occurred in neurobalstoma cells .\napparently lgi1 was capable to counteract efficiently the oncogenicity of hpv , specifically of the viral protein e6 , which prevents apoptosis by stimulating the ubiquitin - mediated degradation of p53 , a transcriptional regulator capable to enhance the expression of bax and to repress that of bcl2 [ 16 , 2729 ] .\nthus the balance of these apoptotic factors imposed by e6 to sustain cell survival might be destabilized by lgi1 in favor of apoptosis .\nalthough the mechanism of cell death induced by lgi1 has not been completely elucidated , it seems possible that lgi1 might interfere with central survival pathways such as the pi3k / akt , as it occurred in neuroblastoma cells , because the prosurvival effects of this pathway includes transcriptional regulation of bcl2 and bax genes [ 30 , 31 ] . in conclusion\n, this study supports the possibility that lgi1 might act as tumor suppressor of adenocarcinoma - derived cells , in line with the downregulation of lgi1 reported in barrett's - related adenocarcinomas and with previous studies on glioblastoma and neuroblastoma cells [ 914 ] .", "answer": "the lgi1 gene was suggested to function as tumor suppressor for its ability to reduce malignant features of glioblastoma cells . in support to this proposal were the findings that overexpression of lgi1 in neuroblastoma cells inhibited proliferation and induced apoptosis . in this study \n we performed stable lgi1 expression in hela cells to examine whether the noxious effect of lgi1 might be extended to cancer cells of diverse origin . \n hela cell clones stably expressing lgi1 exhibited a significant impairment of proliferation and a consistent increase of cell death when compared with control cells lacking expression of lgi1 . \n expression of lgi1 increased the activity of apoptosis effectors caspase-3/7 ; furthermore it downregulated the antiapoptotic bcl2 gene and upregulated the proapoptotic bax gene expression , suggesting that the cause of hela cells death might be an increased susceptibility to apoptosis induced by lgi1 . \n the results suggested that lgi1 is capable to restrain growth and survival of adenocarcinoma cells such as hela .", "id": 553} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneonatal period ( the first 28 days after birth ) , which is the period of various physiological adaptations to the extrauterine life , is a vulnerable time .\nmore than 10 million children die before the age of 5 years , 8 million of whom die before the age of 1 year and more than half of these deaths occur in the first 4 weeks after birth .\nabout 98% of the neonatal deaths occur in developing countries . according to the world health organization ( who )\n, the rate of deaths is 30 times more in the countries with the highest rate compared to the countries with the lowest rate . according to the reports of ministry of health and medical education\n, the index of neonatal death in iran is 16 - 20 deaths out of 1000 survived births , which is higher than that in developed countries . who has urged iran to halve its neonatal death rate by 2015 .\nrisk factors in studying neonatal death are categorized into three groups : prenatal , intrapartum , and postnatal factors . all over the world , infection , preterm delivery , and birth asphyxia contribute to about 87% of neonatal deaths . in most societies , congenital malformations and premature birth\nbabies with low birth weight ( lbw ) and extremely lbw account for 6 - 7% and 1% of babies death , respectively .\nthese causes , however , are the second and third reasons , respectively , which are responsible for one half of the neonatal deaths .\nprematurity is responsible for about 60 - 80% of neonatal deaths all over the world in babies without congenital anomalies . in many cases ,\nneonatal diseases are caused by respiratory problems , of which hyaline membrane disease ( hmd ) can be mentioned as the foremost .\nabout 1.3% of all neonatal deaths are caused by hmd or its complications in premature newborns .\nhave mentioned five main causes of neonatal death , including prematurity , internal bleeding , septicemia , respiratory distress syndrome , and congenital anomalies , while gheibi et al .\nhave reported prematurity ( 68% ) , hmds ( 51% ) , asphyxia ( 13% ) , sepsis ( 13% ) , and congenital cardiac malformations ( 8% ) as the most important causes of neonatal death .\nthe baby 's gender has also been considered as an important factor in his or her death .\none of the most important issues in babies death is suitable management and timely referral of newborn babies with high - risk levels and being hospitalized in neonatal intensive care unit ( nicu ) .\nnicu is a critical section in a hospital , dealing with infections ( e.g. septicemia , pneumonia , surgical infections , and other infections ) that are difficult to control . in the usa ,\nmanagement , appropriate care , and supportive cares are the important factors in preventing babies death .\nrostami et al . have reported that the rescue chances of the babies who have received preventive nasal continuous positive airflow pressure ( ncpap ) are three times higher than the other babies . considering that an analytical and comprehensive study has not been done about the role of neonatal risk factors and the therapy given for hospitalized neonatal death in west azerbaijan ,\nthe study is case control study , wherein the case group included 250 died babies who were hospitalized in the nicu during 2007 - 2009 .\nthe control group also included 250 newborn babies who were hospitalized in the same unit and were discharged alive and healthy after they were given appropriate treatment . only the newborn babies from shahid motahhari therapy - training center\nwere selected in order to homogenize the sample and eliminate some threatening factors ( factors involved in referral , death , etc . ) .\ndata collection was carried out through a researcher - designed questionnaire which was designed based on other studies and scholars points of view .\ninclusion criteria included the babies complete profiles , and the criteria for exclusion included their incomplete profiles .\nthe questionnaire contained six sections ( mother 's and baby 's demographic information , causes of hospitalization , during - treatment complications , therapeutic actions , and causes of death ) for alive babies and five sections for dead ones .\nchi - square test , odds ratio ( or ) , and logistic regression were applied to analyze how the variables were related .\nbased on single - variable analysis , neonatal risk factors affecting the newborn babies hospitalized in the nicu are as follows : 51.6% of case babies and 18.3% of control babies had first - minute apgar score of less than 6 , which proved to have a significant correlation with babies death ( p < 0.001 ) .\nabout 9.6% of babies of case group and 2.4% of babies in the control group had during - birth asphyxia which proved to have a significant correlation with neonatal death ( p = 0.001 ) [ table 1 ] .\nthe distribution of independent variables by independent variables ; p value based on chi - square test in this study , one of the factors causing death of babies hospitalized in the nicu was hmd ; 77.6% of case babies and 44.8% of control babies suffered from this disease ( p < 0.001 ) .\nfourteen percent of case babies and 2% of control babies had sepsis which showed a significant relation with babies death ( p < 0.001 ) . moreover ,\n58.8% of case babies and 71.5% of control babies were born through cesarean section which also proved to have a significant effect ( p < 0.001 ) [ table 1 ] .\ncongenital anomalies have been recognized as one of the significant risk factors of death of babies hospitalized in the nicu .\neight percent of case babies and 2.8% of control babies were reported to have congenital anomalies ( p < 0.001 ) [ table 1 ] . regarding therapeutic actions\n, the results of the study also showed that having ncpap played a significant role in decreasing death of babies hospitalized in the nicu ( p < 0.001 ) .\nthere was also a significant relation between supportive cares and neonatal death ( p < 0.001 ) .\nincreased number of pregnancies also had a significant effect on neonatal death ( p < 0.001 ) [ table 1 ] .\nvariables like lbw , baby 's gender , blood group , history of preterm labor , and consanguinity had no significant role in the death of neonates hospitalized in the nicu . in order to gauge the key effects of the mentioned factors ,\nthe adjusted or calculated from advanced logistic regression model was measured through advance selection method .\nthe results showed that the or of neonatal death was 4.02 times greater for neonates with first - minute apgar score of less than 6 compared to those with first - minute apgar score of 6 and more , for asphyxia , the or was 6.16 , for hmd it was 4.08 , and for sepsis it was 6.42 . applying ncpap and\nmultiparity led to a decrease in the death of neonates hospitalized in the nicu [ table 1 ] .\nin the present study , the most important neonatal risk factors affecting neonatal death were found to be sepsis , birth asphyxia , hmd , first - minute apgar score of less than 6 , congenital anomalies , and delivery method . in our study ,\nthe most common risk factor for neonatal deaths was sepsis which raised the risk of death by infection to 6.42 times more than the other causes .\n, sepsis and its complications were reported to be the first cause of death , but in the investigations of nayeri et al . and amin et al . , sepsis had higher ratings .\nthis may be due to the factor that premature babies are prone to infection , but it should be more investigated because of the high number of deaths resulting from it .\nthis spread of sepsis has been reported to be in 1 - 10 cases out of 1000 live births , but 10 - 50% of deaths occur because of it . the second risk factor in the present study was at birth asphyxia , which is in line with tariq and kundi 's study which mentioned sepsis and neonatal asphyxia as the main causes of death , but in the studies carried out by sereshtedari et al . , it was the cause of the 16% deaths in 18 provinces of the country , in bangladesh approximately 26% of neonatal deaths are caused by asphyxia .\nthe other serious clinical problem is respiratory difficulty , and in this study , it manifested as respiratory distress and hmd . in our study , it was the third risk factor of infant death .\nthe study of abdul in malaysia showed that this problem with sepsis is the most important cause of infants death .\nthere is also a second leading cause of infant death in tariq and kundi 's study , and respiratory distress syndrome which were studied by kumar et al . in india ,\njehan et al . in pakistan , naghavi in 18 provinces of iran , javanmardi et al . in isfahan , amani et al . in ardebil , and in the studies of nayeri et al . in tehran and sereshtedari\none of the causes of infant death , low apgar score at birth , is increasingly mentioned in many studies to be a risk factor .\nlow apgar score at birth could be correlated to factors such as neonatal infections , birth asphyxia , meconium aspiration , respiratory distress syndrome , and other causes which may result in infant mortality . in our study , ncpap was applied in the control group two times more than in the case group , which resulted in a decrease of babies death by 0.43 .\nin their study , rostami et al . also reported that applying preventive ncpap to newborn babies will increase their survival chances by three times .\ncongenital anomalies was found to be in the second position in the studies of sharifi , hematyar and yarjo , javanmardi et al . in esfahan , and naghavi 's study in 18 provinces .\nit was mentioned as the second and first cause in the studies of sareshtedati et al . and\n's study , congenital anomalies and infection were mentioned as the leading factors of infant death .\nthe rate of abnormalities in our study compared with other studies , which shows that it is a less important factor in the incidence of neonatal death .\nthis may be due to high morbidity and mortality caused by other factors such as immaturity , lack of attention and careful examination at the time of birth , lack of screening for neonatal abnormalities , and not performing autopsy in dead neonates .\ndeath rate in babies with lbw is about 40 times higher than in babies with normal weight . unlike these studies\nthis finding is in correlation with that of nayeri et al . in the present study ,\nnormal vaginal delivery was higher in the case group than that in the control group .\nthis finding shows that cesarean section can be better when there is an emergency case or prematurity .\nalthough emergency cesarean section is performed to save the lives of the mother and baby , the selection is not always uncomplicated . in a study , it has been reported that two - third of babies who died were born through cesarean section . in our study , despite the high level of infant mortality in males , there was no significant relation between gender and the cause of death .\nan important risk factor that was investigated in this study was the number of pregnancies .\nthe results of this investigation showed that death rate decreased as the number of pregnancies increased .\nnumber of births higher than 5 , pregnancy number above 3 , and high rate of birth were mentioned as effective factors causing babies death in studies conducted by shirvani and khosravi , chaman et al .\n, and titaley et al . , respectively . appropriately carrying out care and supportive cares can be effective factors in preventing babies death . in our study ,\n51.6% of case babies and 2.3% of control babies had received supportive care from birth .\nhigher death rate in case babies can be due to bad physical conditions and other threatening factors .\nthe results of the study show that incorrect methods of transfer can increase the death rate . in this study , special attention was devoted to increasing the care standards in order to decrease the death rate . according to the results of the study that took into consideration factors such as age , occupation , consanguinity , blood group , preterm delivery background , and sex in two groups with equal distribution , it can be concluded that factors related to accompanying diseases and care during delivery play a significant role in neonatal death .\ntherefore , regarding the fourth goal of millennium development , decreasing babies death to two - fourths by 2015 in countries with high rate of mortality , it seems to be better to spot pregnancies with high risk of babies death through pre - delivery care and to transfer mothers who are likely to bear premature or sick babies to centers that have nicus . in cases where it is impossible to specify whether a delivery is risky before birth ,\nthe subsequent hospitalization problems can be prevented by providing appropriate conditions of transfer and therapeutic actions in intensive care units .\nthe major risk factors in this study ( sepsis , asphyxia during birth , hmd , congenital anomaly , and apgar score less than 6 in the first minute of birth ) are considered as the major complications of preterm labor and preterm infants .\nso , strict preventive programs should be undertaken for premature preterm labor and preterm infants ; taking care of the infants in four stages ( before conception , during pregnancy , during delivery , and thereafter ) can be highly effective as well .", "answer": "background : a newborn is highly fragile whose death can be caused by embryonic , intrapartum , and postpartum factors . identifying the causes of death is the first step to be taken in order to decrease the death rate . \n the present study was aimed at finding out how neonatal factors and therapeutic actions affect death of newborn babies.materials and methods : the is a case - control study where the case group included 250 dead neonates who were hospitalized in the neonatal intensive care unit during 2007 - 2009 . \n the control group also included 250 newborn neonates who were hospitalized in the same unit and were discharged alive and healthy after they were treated appropriately . \n researcher - designed questionnaires including demographic characteristics of mothers and infants , causes of hospitalization , treatment and its complications , and causes of death were used to collect the required data . \n chi - square test , odds ratio ( or ) , and logistic regression were applied to analyze how the variables were related . \n p < 0.05 were considered significant . \n statistical analyses were carried out using software spss 16.0.results:the results of advanced logistic regression model showed that first - minute apgar less than 6 ( or = 4.02 ) , existence of birth asphyxia ( or = 6.16 ) , hyaline membrane disease ( or = 4.08 ) , and sepsis ( or = 6.42 ) increased the death rate of neonates hospitalized in the intensive care unit , and applying nasal continuous positive airway pressure and multiparity decreased the death rate of newborn babies . \n there was no significant correlation between variables such as low birth weight , consanguinity , blood group , pr eterm labor history , and baby 's gender , and the death rate of neonates.conclusions:the results of the study show that factors such as low apgar score , asphyxia , hyaline membrane disease , sepsis , prematurity and congenital anomalies , and method of delivery have a positive effect on the death of neonates . \n they also prove that suitable management and carrying out appropriate therapeutic actions and intensive care decrease the death rate of newborn babies .", "id": 554} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na newly diagnosed acromegaly patient aged 45-year - old woman was referred to our clinic for an ophthalmologic examination from the endocrinology department of our hospital .\nserum igf-1 level was 750 ng / ml ( reference ranges of igf-1 in ages 4685 : 94166 ng / ml ) .\ncomplete ophthalmological examination including cct with ultrasonic pachymetry ( tomey corporation , nagoya , japan ) , and standard threshold perimetry with the humphrey visual field analyzer 24 - 2 program ( carl zeiss meditec , inc . ,\ndublin , ca , usa ) were performed . after informed consent was obtained from the patient , basal tear samples were collected atraumatically from the inferior tear meniscus of both eyes using glass capillary tubes or micropipettes .\ntear samples were diluted in phosphate - buffered saline , placed in microtubes , and stored at 70c until further examination .\ntear igf-1 concentrations were measured using a commercial enzyme - linked immunosorbent assay kit ( quantikine , r and d systems , minneapolis , mn , usa ) according to the manufacturer 's instructions .\ntear igf-1 level was 0.63 ng / ml . best - corrected visual acuities were 1.0 in both eyes .\noptic disc examination revealed normal in both eyes ( cup - to - disc ratio was 0.3 in both eyes ) .\ncct was 615 m in the right eye and 612 m in the left eye .\niop levels were 24 mm hg in the right eye and 23 mm hg in the left eye .\nafter the patient was referred to a neurosurgery by the endocrinology clinic for an operation , he underwent transsphenoidal adenectomy for the pituitary adenoma .\nthe patient 's serum igf-1 values had fallen to 125 ng / ml . besides tear igf-1 values were 0.32 ng / ml .\ncct was 585 m in the right eye and 575 m in the left eye .\niop levels were 20 mm hg in the right eye and 19 mm hg in the left eye .\nanother newly diagnosed acromegaly patient aged 55-year - old woman was referred from endocrinology clinic for an ophthalmologic examination .\nserum igf-1 level of the patient was 1340 ng / ml . tear igf-1 level was 0.98 ng / ml .\ncct was 595 m in the right eye and 590 m in the left eye .\niop levels were 22 mm hg in the right eye and 21 mm hg in the left eye .\noptic disc examination were also normal in both eyes ( cup - to - disc ratio was 0.4 in both eyes ) .\nthe patient also was referred to the neurosurgery department for an operation , and she also underwent pituitary surgery .\nthree months after surgery the patient 's complete ophthalmological and visual field examination revealed normal .\nserum igf-1 value had fallen to 389 ng / ml . besides tear igf-1 value was 0,25 ng / ml .\ncct values were 565 m in the right eye and 560 m in the left eye .\niop levels were 18 mm hg in the right eye and 17 mm hg in the left eye .\na newly diagnosed acromegaly patient aged 45-year - old woman was referred to our clinic for an ophthalmologic examination from the endocrinology department of our hospital .\nserum igf-1 level was 750 ng / ml ( reference ranges of igf-1 in ages 4685 : 94166 ng / ml ) .\ncomplete ophthalmological examination including cct with ultrasonic pachymetry ( tomey corporation , nagoya , japan ) , and standard threshold perimetry with the humphrey visual field analyzer 24 - 2 program ( carl zeiss meditec , inc . ,\ndublin , ca , usa ) were performed . after informed consent was obtained from the patient , basal tear samples were collected atraumatically from the inferior tear meniscus of both eyes using glass capillary tubes or micropipettes .\ntear samples were diluted in phosphate - buffered saline , placed in microtubes , and stored at 70c until further examination .\ntear igf-1 concentrations were measured using a commercial enzyme - linked immunosorbent assay kit ( quantikine , r and d systems , minneapolis , mn , usa ) according to the manufacturer 's instructions .\ntear igf-1 level was 0.63 ng / ml . best - corrected visual acuities were 1.0 in both eyes .\noptic disc examination revealed normal in both eyes ( cup - to - disc ratio was 0.3 in both eyes ) .\ncct was 615 m in the right eye and 612 m in the left eye .\niop levels were 24 mm hg in the right eye and 23 mm hg in the left eye .\nafter the patient was referred to a neurosurgery by the endocrinology clinic for an operation , he underwent transsphenoidal adenectomy for the pituitary adenoma .\nthe patient 's serum igf-1 values had fallen to 125 ng / ml . besides tear igf-1 values were 0.32 ng / ml .\ncct was 585 m in the right eye and 575 m in the left eye .\niop levels were 20 mm hg in the right eye and 19 mm hg in the left eye .\nanother newly diagnosed acromegaly patient aged 55-year - old woman was referred from endocrinology clinic for an ophthalmologic examination .\nserum igf-1 level of the patient was 1340 ng / ml . tear igf-1 level was 0.98 ng / ml . best - corrected visual acuities were 1.0 in both eyes .\ncct was 595 m in the right eye and 590 m in the left eye .\niop levels were 22 mm hg in the right eye and 21 mm hg in the left eye .\noptic disc examination were also normal in both eyes ( cup - to - disc ratio was 0.4 in both eyes ) .\nthe patient also was referred to the neurosurgery department for an operation , and she also underwent pituitary surgery .\nthree months after surgery the patient 's complete ophthalmological and visual field examination revealed normal .\nserum igf-1 value had fallen to 389 ng / ml . besides tear igf-1 value was 0,25 ng / ml .\ncct values were 565 m in the right eye and 560 m in the left eye .\niop levels were 18 mm hg in the right eye and 17 mm hg in the left eye .\nin acromegaly , normalization of igf - i in serum has been used to follow - up the success of surgical and medical therapies .\nvan setten et al . reported that the igf-1 level was elevated not only in the serum , but also in the subretinal fluid and aqueous humor in a patient with acromegaly .\nthis study inspired us to hypothesize that the eyes might be another target organ for the effects of excess gh and igf-1 , hence in our study we measured tear igf-1 levels and evaluated the relationship with cct and iop before and after treatment in two acromegaly patients .\nciresi et al . emphasized that high gh may have stimulatory effects on the cornea , as well as on other target organs .\nbramsen et al . divided 27 pituitary adenoma patients into two groups as those with and without acromegaly and reported higher cct values in the group with acromegaly .\nin contrast , polat et al . reported no statistically significant difference regarding median right and left corneal thicknesses and mean cct values between acromegaly and control groups .\nthey divided 30 patients with acromegaly into two groups as those with active and inactive .\nwe think that possible growth effect of tear igf-1 may have an impact on cct .\nwe found a higher cct , iop , and tear igf-1 values in the active phase of the disease .\nthe activity of the disease may have an impact on ocular parameters such as cct , iop , and tear igf-1 values .\nhowever , longitudinal studies including larger populations and controls are needed to confirm this relationship .", "answer": "the aim of the study was to compare the central corneal thickness ( cct ) , intraocular pressure ( iop ) , and tear insulin - like growth factor-1 ( igf-1 ) levels of 2 patients with acromegaly before and after the surgical treatment of the disease . \n ccts , iop levels , and tear igf-1 values showed a decrease after the treatment in 2 patients . as we found higher cct , iop , and tear igf-1 levels in the active phase of the disease in two acromegaly patients , detailed information about the activity of the disease may be important before the examination of these patients .", "id": 555} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n women with psychiatric diseases are treated with antipsychotic medication(s ) with limited evidence to support the safety of their use during pregnancy.olanzapine , a second - generation antipsychotic , is a us food and drug administration pregnancy category c drug with no unequivocal evidence of harm to the fetus.we report the first case of tracheo - esophageal fistula as a possible teratogenic effect of olanzapine exposure . \n\nwomen with psychiatric diseases may become pregnant and are treated with antipsychotics without any proven evidence of safety . due to ethical issues , pregnant women\nare rarely included in clinical trials , leading to a dearth of data available on the safety of antipsychotic drugs in this population .\nthere have been reports of congenital anomalies in newborns of mothers exposed to antipsychotic medications during pregnancy [ 14 ] .\nolanzapine , a second - generation antipsychotic , is a us food and drug administration ( fda ) pregnancy category c drug [ 3 , 5 ] with no unequivocal evidence of harm to the fetus .\na literature search revealed that maternal exposure to olanzapine appears to be associated with lumbar meningomyelocele , dysplastic kidney , hip dysplasia , atrioventricular canal defect , club foot , microcephaly , ventricular septal defect , absent fingers , craniosynostosis , cleft lip , encephalocele , aqueductal stenosis , etc .\nthe possibility of further teratogenic effects of olanzapine can not be ruled out . in this case report , we report the first case of tracheo - esophageal fistula ( tef ) as a possible teratogenic effect of olanzapine exposure .\nwe report the case of a 29-year - old married woman with bipolar disorder with mixed episodes who had been treated with olanzapine in the psychiatric outpatient department of our institute ( lady hardinge medical college , new delhi , india ) for the last 7 years who delivered a full - term female baby with tef in september 2013 .\none week after her marriage in february 2008 , the patient developed psychotic symptoms such as excessive talking , episodes of crying and laughing , and forgetting things frequently .\nfollowing initial unsuccessful local treatment , she was taken to the psychiatry department of a tertiary care hospital .\nafter initial management of acute symptoms there , she continued her treatment from our institute , where she was prescribed olanzapine ( oleanz 10 mg tablet orally once daily ) . in december 2008 , she had a miscarriage at 4 months gestation , following which she stopped taking the medication of her own choice . a careful history / enquiry from the parents failed to reveal any data available regarding congenital malformation of the aborted fetus . in 2009\n, she conceived again ( it is noteworthy that the patient was not taking olanzapine during this pregnancy ) and delivered a full - term healthy female child in january 2010 .\neight months after delivery of this baby the patient had a recurrence of psychotic symptoms for which she was prescribed the same treatment . in december 2012 , she conceived a third time but due to persistent psychiatric symptoms , olanzapine was continued throughout the pregnancy by the treating psychiatrist , who considered there to be a favorable benefit : risk ratio for the patient at that time .\nshe received regular antenatal care and was compliant with all prescriptions and instructions , including prophylactic folic acid and two doses of tetanus toxoid .\nthere was no history of maternal alcohol intake , smoking , or exposure to other potential teratogenic drugs or exogenous hormones throughout the pregnancy .\nall baseline hematological ( hemoglobin 13.8 g / dl , total leukocyte count 6000/l , platelets 2.3 lac/l , etc . ) and biochemical investigations ( random blood sugar 98 mg / dl , blood urea 27 mg / dl , etc . )\ntests for trisomy 21 and 18 ( nuchal translucency scan and dual marker tests ) and rubella were negative .\n, she delivered a full - term female baby by vaginal delivery . immediately after delivery ,\nthe baby experienced respiratory distress and excessive salivation , for which she was admitted to the neonatal intensive care unit . on examination ,\na red rubber catheter could not be negotiated beyond 10 cm in the esophagus .\nother concomitant anomalies including vertebral , anal , renal , limb ( components of vacterl [ vertebral defects , anal atresia , cardiac defects , tracheo - esophageal fistula , renal anomalies , and limb abnormalities ] ) , eye , ear , and nasal defects were ruled out .\nthe tef was repaired using esophageal esophageal anastomosis with a drainage tube in the fifth intercostal space . on the second post - operative day\nfor this reason , cervical esophagotomy was performed and a gastrostomy was inserted for feeding purposes .\nthe baby was discharged in a stable condition with advice for full breast milk feeding through gastrostomy , some required medications ( multivitamin syrup , calcium , anti - emetic and antibiotics ) for an appropriate duration , and regular vaccination . however , although the baby was well until this point , she was re - hospitalized at 11 months of age because of diarrhea and unfortunately died on 19 august 2014 , probably because of widespread infection ( no definitive record of the last hospitalization is available and a post - mortem was not performed).fig . \n1chest x - ray posteroanterior view of the newborn baby , who was born to a mother with antenatal exposure to olanzapine , suggestive of tracheo - esophageal fistula \n chest x - ray posteroanterior view of the newborn baby , who was born to a mother with antenatal exposure to olanzapine , suggestive of tracheo - esophageal fistula\na number of drugs are clearly known to be associated with teratogenicity , such as thalidomide and isotretinoin , but the majority of drugs do not have conclusive data concerning their effect on fetal development and growth . due to strict ethical constraints , at - risk populations ( including pregnant women ) are not included in most clinical trials , limiting the availability of data on the use of drugs ( including antipsychotics ) in these populations , and thus spontaneous reporting of suspected adverse drug effects constitutes an essential tool for generating data on the safety of drugs , especially in the population of pregnant women . according to a retrospective analysis of data from the lilly safety database , of the 610 prospectively identified pregnancies exposed to olanzapine with an available outcome\n, there were 401 ( 66% ) normal births , 60 ( 9.8% ) premature births , 57 ( 9.3% ) spontaneous abortions , 49 ( 8% ) perinatal complications , 27 ( 4.4% ) congenital anomalies ( cleft lip , encephalocele , and aqueductal stenosis ) , and 16 ( 2.6% ) other outcomes ( post - perinatal condition , ectopic pregnancy , post - term birth , and still birth ) .\nother reported congenital anomalies with olanzapine included meningocele , ankyloblepharon , hip dysplasia , acheiria , atrioventricular canal defect , and unilateral club foot [ 1 , 68 ] . a link between teratogenicity and antipsychotics\nis also supported by the fact that these drugs readily cross the placental barrier [ 1 , 4 , 9 ] , with 23.8% placental passage for quetiapine and 72.1% for olanzapine [ 2 , 4 , 9 ] .\nnewport et al . measured placental passage of medication from mother to fetus by measuring levels in the umbilical cord serum and found that olanzapine has the highest rate of placental passage , compared with haloperidol , risperidone , and quetiapine [ 3 , 9 ] .\nthe overall incidence of esophageal atresia / tef ranges from one in every 2500 to 4500 live births .\nhowever , a careful literature search revealed a paucity of data on the incidence of tef in children born to women with psychiatric disease and the problem of confounding by indication can not be ruled out .\nit has been proposed that antipsychotics interfere with the action of calmodulin , which has an important role in organogenesis .\nesophageal atresia and abnormalities of pharyngeal glands have also been proposed as being related to neural crest cells .\nthe drugs ( olanzapine in this case ) associated with such anomalies may be hypothesized to cause neural crest cell damage during early fetal development as a causative factor . although the neural crest cell damage - related esophageal abnormalities in many cases are also associated with cardiovascular anomalies , these were absent in the present case .\nwe tried to establish the causality between the adverse outcome ( tef ) and use of olanzapine during pregnancy according to the who - umc ( world health organization \nuppsala monitoring centre ) adverse drug reaction causality assessment scale and the naranjo causality assessment scale .\ncausality is probable ( score + 5 ) as per the naranjo scale , whereas it is \none of the important reasons for lower scores of causality is the non - applicability of many questions in these scales .\nthe current case report of tef associated with antenatal olanzapine exposure demonstrates the need for large clinical studies to generate more conclusive data concerning use of this drug during pregnancy .\non the basis of the present case and the literature , it is suggested that antenatal olanzapine exposure may be related to the development of tef in newborns .\nhowever , the present case report can only be considered as preliminary evidence and further observational prospective studies of women with antenatal exposure to olanzapine should be conducted to explore the strength of association between tef and olanzapine .\nknowledge of the teratogenic potential of a drug is essential to prevent / reduce the morbidity and mortality associated with a congenital anomaly ( tef in this case ) .\nsuch post - marketing reports are effective tools to disclose the adverse effects of drugs , which are difficult to detect in clinical trials and may factually change the safety status of a drug .\nwritten informed consent was obtained from the infant s father for publication of this case report .", "answer": "there is a dearth of evidence on the safety of the use of antipsychotics during pregnancy . \n olanzapine , a pregnancy category c drug , has no unequivocal evidence of harm to the fetus . against this backdrop \n , we report the first case of a tracheo - esophageal fistula ( tef ) in a newborn following maternal antenatal exposure to olanzapine . \n a 29-year - old woman with acute psychotic disorder had been treated with olanzapine for the last 7 years . her first pregnancy , while taking olanzapine , resulted in a miscarriage at 4 months gestation , following which she discontinued olanzapine . \n she reconceived after a few months and delivered a full - term normal child . \n however , due to the recurrence of psychiatric illness after her second pregnancy , she was prescribed olanzapine again , which was continued throughout her third pregnancy . \n the outcome of the third pregnancy was a full - term female baby with a tef . \n the baby was managed surgically and discharged with satisfactory vital signs . \n unfortunately , however , the baby did not survive beyond 11 months of age . \n causality between antenatal maternal olanzapine exposure and tef in the newborn was determined to be \n probable ( score + 5 ) as per the naranjo causality assessment scale . \n greater knowledge of this potential teratogenicity caused by olanzapine is needed to reduce morbidity and mortality in newborns .", "id": 556} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncurrarino syndrome ( cs ) is a hereditary pathology that is characterized by a triad of malformations : sacrococcygeal bone defect , presacral mass , and anorectal malformation .\nradiologic imaging modalities such as ultrasonography ( us ) , computed tomography ( ct ) , and magnetic resonance imaging ( mri ) play a vital part in diagnosis and follow - up of this pathology . in this report , we aim to present the magnetic resonance imaging ( mri ) findings of a case with complete cs recognized in adulthood .\na 20-year - old male patient who underwent anal atresia operation in childhood was referred to our department for evaluation of anal sphincter status with transrectal us .\ncalibration of one - third of the inferior rectum was observed to be very thin , while one - third of the superior and middle segments of the rectum was seen to be dilated .\nthe left half of s2 and s3 vertebrae , more distal sacral vertebrae , and coccyx were not seen .\nwe also detected anterior meningocele related to spinal canal that originated from the neural foramen of s2 and s3 vertebrae .\nthe lesion was isointense with cerebrospinal fluid in all of the sequences and its size was 4.5 3.5 cm .\n20-year - old man with anal atresia operation history in childhood diagnosed with currarino syndrome .\n( a ) t2-weighted sagittal magnetic resonance image shows calibre of one - third of inferior rectum is very thin ( thick white arrows ) , while superior and middle segments of the rectum are dilated ( arrowheads ) . also , the images demonstrate anterior meningocele ( asterisk ) at the posterior of the rectum related to spinal canal that originated from the neural foramen of s2 and s3 vertebrae .\n( b ) fat - saturated t2-weighted axial magnetic resonance image shows partial cleft at l5 vertebra corpus ( thin white arrow ) and dilated rectum in front of it . on ( c )\nt1-weighted and ( d ) fat - saturated t2-weighted axial magnetic resonance images , left half of the sacrum is not seen . in this part , spinal canal relationship of anterior meningocele ( asterisk ) and its indentation to the adjacent rectum is also observed .\n( e ) t2-weighted coronal magnetic resonance images demonstrate the contiguity of the sacral defect and anterior meningocele ( asterisk ) more clearly ( r = rectum , b = bladder ) .\ncurrarino syndrome is a rare inherited disorder that is characterized by sacrococcygeal bone defect , presacral mass , and anorectal malformation .\nthe complete form of this syndrome shows all three abnormalities and is rarer than the incomplete form which includes one or two of the disease components mentioned above .\nalthough the patients with this syndrome may present with complex conditions like recurrent urinary system infections or meningitis , chronic constipation is the most common finding .\nsome of the cases are asymptomatic and can be diagnosed during adulthood only on x - rays and us examinations that are performed for different reasons .\nin addition to rectal digital examination , x - rays , us , ct , and mri are very helpful in the diagnosis of the syndrome .\nsacrococcygeal bone defect is a prerequisite for the diagnosis of cs and its spectrum changes from mild lateralization of the coccyx to multilevel hypoplasia of the sacral segments ( scimitar sacrum ) . in our case\n, there was partial cleft at l5 vertebra corpus and s1 vertebra was partially deformed . also ,\nthe left half of s2 and s3 vertebrae , more distal sacral vertebrae , and coccyx were absent .\nrectal and/or anal stenosis which may be fistulized to ascending spinal canal is the most common anorectal malformation which is seen in cs .\nanal atresia or ectopy , imperforated anus , rectal duplication , and rectourethral , rectovaginal , and rectovesical fistulas may be also associated with the syndrome . in our patient ,\nthere was heterogeneity of the cutaneous and subcutaneous soft tissue around the anus secondary to earlier anal atresia operation .\nenteric cyst , lipoma , hamartoma , dermoid and epidermoid cysts may be seen as well .\nus , ct , and mri are frequently used for diagnosing the mass lesion and determining its nature .\nmri is an invaluable technique to recognize accompanying additional pathologies like tethered cord , syringomyelia , and intradural lipoma . in our patient\n, we detected a 4.5 3.5 cm size anterior meningocele related to the spinal canal .\ncloacal malformation with anal atresia , double vagina , rectovesical fistula , urogenital sinus , neurogenic bladder , vesicoureteral reflux , and multicystic kidney are other related pathologies of cs .\nmri is a very useful imaging modality to diagnose cs and accurately detect all the three components .\nbesides , it can show the different aspects of other cloacal malformations including the uterus , vagina , maldeveloped puborectalis , and external anal sphincter .\nalthough these anomalies are not surgically correctable , early detection almost always provides better prognosis and helps in patient management .\nanother major advantage of mri over other imaging modalities is the ability to detect associated anomalies of anorectal malformations , especially of the spinal cord , spine , and urogenital system .\nkassir et al . , also reported that mri is a specific and sensitive non - invasive diagnostic tool in patients with anorectal malformations .\nmri provides excellent information about the postoperative anatomy of anorectal malformations . due to its superior soft tissue characterization , multiplanar imaging ability , and lack of ionizing radiation exposure\nthese unique features make mri a very appropriate modality in follow - up of patients treated for anorectal abnormalities .\nthe treatment strategy changes based on the type of pathology . the management of the anorectal anomaly and presacral mass may be performed with single - stage surgical procedure .\nif the mass is a meningocele , a staged operation must be preferred due to the risk of meningitis .\ncs should be obviously considered in patients with sacrococcygeal bone defect , presacral mass , and anorectal malformation .\nmri may be used safely in diagnosis of the syndrome , in detecting the accompanying mass lesions and other pathologies , and in the follow - up investigations after treatment in patients with cs .", "answer": "currarino syndrome is a hereditary pathology that is characterized by sacrococcygeal bone defect , presacral mass , and anorectal malformation . \n sacrococcygeal bone defect is almost always a part of the syndrome . \n the complete form of this entity displays all three abnormalities and is very uncommon . in this report , \n we present the magnetic resonance imaging findings of a case with complete form of currarino syndrome recognized in adulthood .", "id": 557} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntype iii dysbetalipoproteinaemia is a kind of lipid metabolism disorders , caused by apo - e deficiency , which leads to accumulation of chylomicrons and very low density lipoprotein remnants in the plasma.123 lipid metabolism disorders are mostly manifested by xanthomas , which are known as yellowish cholesterol - rich material in large foam cells accumulating in the skins and tendons.14 these yellowish lesions may appear all over the body , on the palm of the hands , sole of the foot , tendons , and even on the eyelids.5 these lesions firstly described with or without hyperlipidaemia in association with monoclonal immunoglobulin . based on this fact , there are three forms of xanthoma : hyperlipaemic xanthoma , normolipaemic xanthoma and necrobiotic xanthogranuloma.6 xanthomatosis is usually associated with hyperlipidaemia , and morbidity and mortality of this condition are related to atherosclerosis and pancreatitis.7 hyperlipaemic xanthoma lesions are more polymorphic and can include tuberous , tendinous , palmar or eruptive xanthoma .\nverruciform xanthoma usually presents as a hyperkeratotic , cauliflower like , verrucous or papillomatous lesion.6 it initially was described as a unique clinicopathologic lesion of the oral mucosa and was subsequently reported in the skin .\nthe epidermal - mucosal changes of hyperparakeratosis , neutrophilic infiltrate and dermal - submucosal foam cell reaction are distinctive features of these xanthomas.8 hereby , we present a rare type of xanthomas calling cauliflower xanthoma in a 43-year - old man with dysbetalipoproteinaemia .\na 43-year - old man was presented to outpatient endocrine clinic of tabriz university of medical sciences , tabriz , iran , by his sister for evaluation of skin lesions .\nhe had multiple lesions on shoulders and back , lateral and medial part of dorsal surface of the foot , medial and lateral malleus of both feet , and dorsal and palmar surface of both hands .\nsiblings of the patient have been followed up in that clinic for clinically diagnosed type - iii dysbetalipoproteinaemia .\nthis diagnosis was based on characteristic palmar , eruptive , tuberous and trauma site xanthomas with typical high levels of both total cholesterol and triglycerides in the plasma .\nhistory of coronary artery or other atherosclerotic disorders were negative in index case and siblings .\nthere were not any other complaint , and as a greengrocer , he had an active lifestyle .\nhe had a pathology report of skin lesion biopsy that was performed by a dermatologist few months ago , with presence of lipid laden macrophages consistent with diagnosis of xanthoma . fasting serum lipid levels reported as : total cholesterol = 507 mg / dl , triglycerides = 470 mg / dl and high density lipoprotein ( hdl ) cholesterol = 41 mg / dl .\nhe had normal fasting blood sugar , and normal thyroid , renal and liver function tests .\nphysical examinations revealed numerous xanthomas resembling cauliflower on both knees [ figure 1 ] , unusual eruptive , tuberous xanthomas same as previous lesions , on the lateral malleus of both feet [ figure 2 ] .\ncauliflower xanthomas on the knees and lateral malleus of both lower extremities cauliflower xanthomas on the lateral malleus of lower extremities there were lots of smaller xanthomas on the right shoulder [ figure 3 ] , and cauliflower like xanthomas on the extensor side of the left upper extremity , especially on the elbow [ figure 4 ] . based on available information\n, the patient diagnosed as familial dysbetalipoproteinaemia ( fdl ) and the unique lesions on the lower limb called cauliflower xanthoma .\nalthough siblings of this case had the same disorder , they did nt develop such lesions .\nxanthomas on the shoulder and back of the neck xanthomas on the extensor side of the hand by searching in the medical data bases , we can not find a previous such a lesion . therefore , we decided to present this case without revealing patient 's name , after taking his consent .\nconsidering the fact that the treatment with high dose statin was effective in correction of lipid abnormality and regression of skin lesions in his three siblings , we wanted to try the treatment procedure in this patient but he refused any intervention .\nfdl , also known as hyperlipoproteinemia type - iii or broad beta disease , is a rare inherited disorder characterised by improper metabolism of certain lipids , specially plasma cholesterol , triglyceride rich chylomicron and very low density lipoproteins ( vldl ) remnants.1 presence or absence of the symptoms of this disease depends on two major risk factors : genetic and diet.910 mutations in the gene for apolipoprotein e ( apo e ) are the main cause of this disease .\nreplacement of an arginine by a cysteine in position 158 of the 299-amino acid chain of apo e5 is responsible for the defective binding of chylomicron and vldl remnants to cell receptors .\nthereafter , slower plasma clearance of these particles occurs , and results in the abnormal accumulation of lipids in the body.9 on the other side , diet has an essential role in the development of the disease .\nthis means that with standard cholesterol diet , symptoms of fdl will not appear , even in the genetically susceptible person.10 xanthomas can be a symptom of fdl .\nxanthomas may also be the symptoms of a generalised histiocytosis , or a local fat phagocytosing storage process.11 they are yellowish lesions on the skins and tendons , macroscopically .\nthese macrophages are filled with lipid droplets , which are dissolved and removed from tissue during histologic processing.8 fdl is mostly diagnosed by combination of clinical and laboratory findings.12 most cases are inherited as autosomal recessive trait .\nmen are more susceptible for fdl probably because of protective impact of estrogen in women .\nmost of the diagnosed patients were typically young males , with strong family history , characteristic skin lesions , high serum levels of cholesterol and triglycerides and confirming skin histology.113 most of these cases have premature atherosclerosis and other signs of ischaemic disorders.9 the patient in this article was a middle aged man with family history of dysbetalipoproteinaemia and high levels of serum lipids as follows : total cholesterol = 507 mg / dl and triglycerides = 470 mg / dl .\nhe had a rare form of xanthoma all over his body , causing social problems for him .\nnicotinic acid , clofibrate , statins or gemfibrozil properly reduce cholesterol and triglycerides in people affected with dysbetalipoproteinaemia.1 the patient mentioned in this article refused receiving any medical intervention .\nhe has just been advised to have low lipid diet , fish oil and regular moderate exercise in order to reducing serum lipid levels .\nthere should be distinctive monitoring of fdl patients including regular checking of their serum lipids .\ncontrolling underlying disorders , and reducing excess calories , saturated fat and cholesterol , is the main aim of treating these patients . according to this article\n, cauliflower xanthomas could be a symptom of fdl , and it should be considered as a differential diagnosis while approaching to these lesions .", "answer": "familial dysbetalipoproteinaemia ( fdl ) is an inherited disorder in which both cholesterol and triglycerides are elevated in the plasma , pre - disposing the people to coronary artery disease and peripheral vascular disease . \n the disease is mostly manifested by xanthomas , which have variable forms according to lipid amounts in the plasma of the blood . \n hereby , we report a 43-year - old man with fdl , presenting with a rare form of xanthomas calling cauliflower xanthoma all over the body .", "id": 558} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe report a case , carbon dioxide ( co2 ) embolism a potentially devastating complication of laparoscopic surgery , during dissection phase and was successfully resuscitated .\na 35-years - old female , weighing 42 kg was posted for transperitoneal laparoscopic boari 's ureteric reimplantation .\nher , physical examination and routine investigations were unremarkable . with routine monitoring , balanced general anesthesia was given .\nco2 pneumoperitoneum was created uneventfully using open insufflation technique and sustained with pressure of 14 mm hg .\nafter 2 h , when the surgeon was dissecting the ureters , there was a sudden drop in etco2 ( 8 mm hg ) , tachycardia ( 130/min ) followed by multiple ventricular premature beats ( vpbs ) with blood pressure ( bp ) 110/72 mm of hg and sao2 - 98% .\nsurgical bleeding and endotracheal tube blockage were ruled out , and gas embolism was suspected .\ninjection lignocaine 80 mg intravenously was given for vpbs , and the regular rhythm was restored with the heart rate of 42/min .\nat this point , the sao2 decreased from 98% to 77% while the breath sounds were normal with no adventitious sounds .\nsince there was no response to these measures , injection dopamine 20 ug / kg / min and nor - adrenaline 0.36 ug / kg / min were infused .\nmultiorifice central venous catheter with its tip at the superior vena cava -right atrium ( svc - ra ) junction was inserted via right internal jugular vein but air could not be aspirated .\nafter 20 min , resuscitative efforts were successful , patient had pulse rate of 120/min , bp 100/54 mm / hg , sao2 100% , etco2\n30 mm / hg and ecg showed sinus rhythm with right ventricular strain pattern.at this time the cvp was found to be 10 mm of hg .\ntwo - dimension echocardiography ( 2-d echo ) showed no patent ductus arteriosus or any other congenital defects .\nshe was shifted to intensive care unit with dopamine 5 ug / kg / min . which was tapered and stopped after h. the patient did not receive hyperbaric oxygen as we did not have the facility .\nco2 embolism can occur either during peritoneal insufflationor during the surgical dissection . in this case ,\npossible causes of sudden cardiovascular collapse like hypovolemia , hemorrhage , vaso - vagal reflex , pneumothorax and endotracheal tube blockage were ruled out before considering gas embolism the adhesions caused by previous surgery might have led to vascular injury during dissection and the operating site was above the level of the heart ( trendelenburg position ) creating a pressure gradient thus the open venous channels , at lower pressure were open to gaseous medium at a higher pressure leading to gas embolism . either , slow infusion of air ( 0.01 - 2.00 ml / kg / min ) or bolus of gas ( 25 - 200 ml or 1 - 13 ml / kg ) , creates a gas \nparadoxical air embolism was ruled out by a 2-d echo that showed no intra - cardiac channels .\nany kind of pulmonary embolism leads to sudden deterioration of the hemodynamic status associated with decreased etco2 levels . since co2 is a highly soluble gas ( 54 ml / dl ) , prompt recovery of the vital signs is usual .\naspiration of gas through central venous catheter is the definitive means of treating gas emboli . in our case ,\nfailure to aspirate the gas may suggest that it might have been trapped in the pulmonary vasculature .\ntee is the gold standard for detection of pulmonary air embolism , however , it is not indicated routinely for intra - operative monitoring .\nsudden decrease in etco2 is an early sensitive but nonspecific sign of venous air embolismprecordial stethoscope enhances specificity of etco2 and mean pulmonary artery pressure values .\nimmediate treatment of gas embolism requires deflation of pneumoperitonium , placing the patient in durant 's position , hyperventilation and administration of 100% oxygen .\naggressive cardiopulmonary resuscitation should be continued till the acute effects of the embolism abate and one should maintain positive circulating volume to prevent further entrainment of the gas .\nthus , in laparoscopic surgeries early detection of gas embolism with prompt resuscitation can result in a favorable post - operative outcome .", "answer": "carbon dioxide ( co2 ) embolism is a rare but potentially fatal complication of laparoscopic surgery . \n we report a case of presumed co2 embolism in a 35-year - old female during laparoscopic ureteric reconstructive surgery . \n after 2 h of operating time , a sudden decrease in end - tidal carbon dioxide and deterioration of hemodynamic status followed by cardiac arrest with pulseless electrical activity suggested gas embolism . \n immediate cardiopulmonary resuscitation and inotropic support resulted in successful outcome . \n thus , early recognition of the complication and prompt treatment can avoid catastrophy .", "id": 559} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nplasmodium falciparum is one of the major causes of mortality among children in rural india .\nstates such as odisha have high childhood mortality due to p. falciparum positive malaria often occurring in various forms .\nlack of awareness of atypical manifestation leads to delay in diagnosis and early management often leading to death .\nupsurge of unusual features are due to development of immunity , increased resistance and injudicious use of antimalarial drugs .\na 15-month - old male child was admitted with the chief complains of high - grade fever for 7 days followed by altered sensorium for 1 day . on examination , child was febrile and unconscious .\nthe child had uneventful perinatal history , no developmental delay , and no history of seizure .\nblood investigations showed hb was 5.8 mg / dl ; total leucocyte count 12,400/cumm , and total platelet count 65,000/cumm .\nmpict ( antigen test ) was positive and peripheral smear showed multiple rings of p. falciparum .\npatient was treated using intravenous ( iv ) artesunate followed by act according to who guidelines . on follow - up fever decreased and sensorium improved , but on day 4 of the treatment child developed bilateral nystagmus with rapid component towards the right side .\nafter ruling out all other causes of nystagmus , it was diagnosed as an early complication of cerebellar involvement due to severe malaria .\na 6-year - male child was admitted with the chief complain of high - grade fever for 4 days with abnormal behavior and occasional vomiting .\nhe had no history of hematemesis , melena , bladder bowel abnormality , abnormal movement or altered sensorium .\nall vitals signs were normal except for mild tachycardia . on abdominal examination , liver was around 6 cm palpable .\nblood investigation suggested hb was 7.2 mg / dl while other complete blood count ( cbc ) parameters were normal .\npatient coming from an endemic region with high - grade fever , antigenic positivity , and the absence of other risk factors for psychosis confirmed diagnosis of malaria with psychosis .\nchild was treated by iv artesunate with sedatives ( iv lorazepam ) . on day 4 ,\na 11-year - old child was presented to pediatric outpatients department with severe crampy and episodic abdominal pain with urticarial rash over face and abdomen and generalized malaise and lethargy .\nhe had no history of recent fever , seizure , conjunctivitis , abnormal vomiting , and bowel bladder anomaly .\nhe was treated using antihistaminic and antispasmodics ( injection cyclopam , injection ranitidine , and oral cetirizine tablet ) . on day 2 of admission\nas a child was from an endemic region of p. falciparum , mpict ( antigen ) was performed .\niv artesunate was initiated according to who protocol along with antihistamines and antispasmodics ( injection cyclopam 10 mg / dose t.d.s , injection ranitidine\nurticaria in a malaria endemic patient nonresponsive to antihistamine drugs is an indication of underlying malaria and should be managed accordingly .\na 15-month - old male child was admitted with the chief complains of high - grade fever for 7 days followed by altered sensorium for 1 day . on examination , child was febrile and unconscious .\nthe child had uneventful perinatal history , no developmental delay , and no history of seizure .\nblood investigations showed hb was 5.8 mg / dl ; total leucocyte count 12,400/cumm , and total platelet count 65,000/cumm .\nmpict ( antigen test ) was positive and peripheral smear showed multiple rings of p. falciparum .\npatient was treated using intravenous ( iv ) artesunate followed by act according to who guidelines . on follow - up fever decreased and sensorium improved , but on day 4 of the treatment child developed bilateral nystagmus with rapid component towards the right side .\nafter ruling out all other causes of nystagmus , it was diagnosed as an early complication of cerebellar involvement due to severe malaria .\na 6-year - male child was admitted with the chief complain of high - grade fever for 4 days with abnormal behavior and occasional vomiting .\nhe had no history of hematemesis , melena , bladder bowel abnormality , abnormal movement or altered sensorium .\nall vitals signs were normal except for mild tachycardia . on abdominal examination , liver was around 6 cm palpable .\nblood investigation suggested hb was 7.2 mg / dl while other complete blood count ( cbc ) parameters were normal .\npatient coming from an endemic region with high - grade fever , antigenic positivity , and the absence of other risk factors for psychosis confirmed diagnosis of malaria with psychosis .\nchild was treated by iv artesunate with sedatives ( iv lorazepam ) . on day 4 ,\na 11-year - old child was presented to pediatric outpatients department with severe crampy and episodic abdominal pain with urticarial rash over face and abdomen and generalized malaise and lethargy .\nhe had no history of recent fever , seizure , conjunctivitis , abnormal vomiting , and bowel bladder anomaly .\nhe was treated using antihistaminic and antispasmodics ( injection cyclopam , injection ranitidine , and oral cetirizine tablet ) . on day 2 of admission\nas a child was from an endemic region of p. falciparum , mpict ( antigen ) was performed .\niv artesunate was initiated according to who protocol along with antihistamines and antispasmodics ( injection cyclopam 10 mg / dose t.d.s , injection ranitidine 1 ml iv bd , and oral cetirizine 5 mg bd ) .\nurticaria in a malaria endemic patient nonresponsive to antihistamine drugs is an indication of underlying malaria and should be managed accordingly .\nalthough orissa state has about 3.6% of the total population of the country , it accounts for 47% of p. falciparum cases and 34% of all reported deaths due to malaria .\nclassic symptoms of severe malaria caused by p. falciparum among pediatric patients include high - grade fever , sweating , jaundice , vomiting , nausea , and pallor . according to who criteria impaired consciousness , prostration , respiratory distress , multiple seizures , jaundice , hemoglobinuria , abnormal bleeding , severe anemia , circulatory collapse and pulmonary edema are features of severe malaria .\nthe unusual features are due to development of immunity , indiscriminate use and increasing resistance of antimalarial drugs .\ncerebellar involvement in p. falciparum malaria can occur during the acute stage of fever as sequelae of cerebral malaria among survivors or as a side effect of drugs , which is evident as delayed cerebellar ataxia .\nhowever , isolated nystagmus in children after severe malaria is very rarely reported although ataxia and tremor are commonly observed .\nthe cerebellar symptoms are due to injury to purkinje cells as a consequence to hyperpyrexia , anemia , hypoglycemia and persistent seizures eventually leading to hemorrhages , small infarction , and the microglial infiltration in purkinje cells of the cerebellum .\nparanoid , agitation , manic symptoms are observed in the acute stage although it can present as confusional state , severe agitation , delirium , delusion , hallucination and transient amnesia in children .\nnevertheless these features generally disappear after treatment but can be observed in few patients following chloroquine use . very rarely psychotic features may be the first manifestation in malaria with persistent abnormality .\ncerebral malaria can disrupt neuropsychological integration during critical developmental periods resulting in several developmental delays .\nit is due to immunological factors , increase vascular permeability and capillary - dilatation due to cell mediators such as histamine , serotonin , heparin , and proteoglycans .\nas observed in our case , rarely ( 1.35 - 25.6% incidence rate ) urticaria may also be present without fever as the primary manifestation .\nalthough the deposition of ige in endothelial cells cause itching followed by urticaria , however this generally subsides after 12 - 48 h of antimalarial management .", "answer": "variable atypical symptoms are commonly observed in malaria caused by plasmodium falciparum especially in endemic tropical nations such as india . \n nystagmus is observed following involvement of the cerebellum especially during the postrecovery phase . \n while psychotic features such as severe agitation , hallucination , paranoia may be the early symptoms of falciparum malaria among pediatric patients , urticaria with or without fever can be the initial manifestation of the disease . \n as the morbidity and mortality of severe malaria are very high in india , these atypical presentations should be considered during diagnosis . \n we believe our report on atypical cases of falciparum malaria will sensitize doctors and health personnel about rare presentations in children and help in early diagnosis and management to reduce the severity and death toll due to the disease .", "id": 560} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe sequenced 12 bat brains positive for lyssavirus antigen detected by immunofluorescence and reverse transcription \nthe 400-bp 5 variable extreme of the nucleoprotein gene of these eblv-1 strains was amplified by specific eblv-1 nested rt - pcr and sequenced by using the following primers : seqvar1f 5-1acgcttaacaaccagatcaaag22 - 3 , seqvar2f 5-51aaaaatgtaacacyyctaca70 - 3 , eblvseqvar1r 5-596cagtctcaaagatctgttccat575 - 3 , and eblvseqvar2r 5-552tagttcccagtattctgtcc533 - 3. all rabies - positive serotine bats came from southern spain ( huelva , seville , murcia , and badajoz ) and were molecularly identified as e. isabellinus ( 8) . an alignment was performed by using clustalx ( www.clustal.org ) to combine the obtained sequences and other available eblv-1 sequences from genbank , including a duvenhage virus used as the outgroup ( table a1 ) . before conducting further analyses , we used jmodeltest ( http://darwin.uvigo.es/software/jmodeltest.html ) to select the best fitting substitution model for our sequences according to the corrected akaike information criterion .\nmaximum - likelihood phylogenies were reconstructed by using phyml ( http://atgc.lirmm.fr/phyml ) software and by using a generalized time - reversible model and the parameter estimated in the analyses .\nmaximum - parsimony analyses were conducted by using paup * 4.0b10 ( http://paup.csit.fsu.edu/ ) weighting transversions 15 according to the transitions / transversion ratio estimated in the jmodeltest analyses .\nconfidence in the topologies for the maximum - likelihood and the maximum - parsimony analyses was established with 1,000 bootstrap replicates .\na bayesian phylogenetic inference was obtained by using mrbayes version 3.1 ( http://mrbayes.csit/fsu.edu/ ) with random starting trees without constraints .\ntwo simultaneous runs of 10 generations were conducted , each with 4 markov chains , and the trees were sampled every 100 generations .\nnet p - distances between groups were calculated by using mega4 ( www.megasoftware.net ) ( figure 1 ) .\neuropean bat lyssavirus 1 ( eblv-1 ) phylogenetic reconstruction based on the first 400 bp of the nucleoprotein gene .\nthe tree was obtained by bayesian inference run for 10 generations ; trees were sampled every 100 generations .\nbootstrap supports after 1,000 replicates for each node are also shown for maximum - parsimony ( green numbers ) and maximum - likelihood ( blue numbers ) analyses .\nnet p - distance values ( as percentages ) between groups are indicated by arrows .\na parsimony - based network is presented for each major lineage ; sizes of yellow circles are proportional to the number of individuals sharing a given haplotype , and reconstructed haplotypes ( median vectors ) are shown in red .\nduvv , duvenhage virus . the genetic structure and relationships between haplotypes were examined within the main lineages through a parsimony - based network built with a median - joining algorithm implemented in the network 4.5.1 program ( 11 ) . to evaluate and compare genetic variability and polymorphism among lineages\n, we estimated the number of haplotypes , mutations , and segregating sites as well as haplotype diversity and nucleotide diversity by using dnasp version 4.5 ( 12 ) for the major clades ( table ) . finally , to investigate population dynamics across lineages , the fu fs and tajima d statistics were calculated ( table ) .\nthese 2 statistics are considered to be the most powerful tests for detecting expansion events ( 13 ) . * eblv , european bat lyssavirus ; n , no .\nsequences ; s , no . segregating sites ; eta , no . mutations ; hap , no . haplotypes ; hd , haplotype diversity ; varhd , haplotype variance ; pi , nucleotide diversity ; thetanuc , estimated population mutation rate per site ; k , average no .\nall phylogenetic analyses , regardless of the reconstruction criterion used , formed a monophyletic cluster of the eblv-1 strains from spain ( only the bayesian inference reconstruction is shown ) .\nthe bayesian inference , maximum - likelihood , and maximum - parsimony analyses identified the cluster from spain and eblv-1a and eblv-1b as being monophyletic ( figure 1 ) , although only maximum - likelihood and maximum - parsimony analyses suggested a closer relationship between eblv-1a and the cluster from spain .\nthe genetic differentiation of the eblv-1 strains from the iberian peninsula matches their association with another bat species ( figure 2 ) , which suggests that the host bat s evolutionary history plays a major role in eblv-1 molecular epidemiology , as has been proposed for rabies virus in bats in north america ( 14 ) .\ngeographic distribution of eptesicus serotinus bats ( red ) , e. isabellinus bats ( blue ) , and cases of rabies in bats ( green dots ) , europe , 19902009 . obtained from rabies bulletin europe ( www.who-rabies-bulletin.org/ ) .\nthe low genetic diversity and the fu fs and tajima d statistics ( table ) all suggest rapid population expansion of eblv-1a , which is consistent with the star - like structure of the network for this lineage ( figure 1 ) .\nconversely , haplotype and nucleotide diversity descriptors ( table ) have the highest values for eblv-1b and a complex network structure with differentiated subnetworks .\nthe lineage from spain also has low diversity and a star - shaped network , but neutral evolution can not be rejected on the basis of the fs and d statistics .\nnet distances are similar within and between lineages , except for eblv-1a , which is slightly more differentiated ( figure 1 ) .\nconsequently , the suggested eblv-1 expansion from spain into europe ( 15 ) is not supported by our results , which record the highest variability and most complex phylogenetic structure for france and the netherlands ( figure 1 ) .\nthis complex structure suggests either a longer evolutionary history in these areas or a recent contact of distinct bat lineages in this zone .\nthe results of this study show that the strains from spain do not belong to subtype 1b because of their association with a different reservoir ( e. isabellinus bats ) .\nmoreover , what is currently considered to be eblv-1b seems to include at least 4 lineages that are more genetically diverse and have a complex history .\neblv-1a , however , has low genetic diversity despite its extensive geographic distribution , suggesting a relatively recent and successful expansion of this lineage .\nthese results call into question the current classification of eblv-1 into 2 single subtypes . to provide a better understanding of eblv-1 molecular epidemiology in europe ,\nadditional studies that consider different genes should be conducted and the current classification should be revised accordingly .", "answer": "to better understand the epidemiology of european bat lyssavirus 1 ( eblv-1 ) in europe , we phylogenetically characterized lyssavirus from eptesicus isabellinus bats in spain . an independent cluster of eblv-1 possibly resulted from geographic isolation and association with a different reservoir from other european strains . \n eblv-1 phylogeny is complex and probably associated with host evolutionary history .", "id": 561} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nHeterogeneous palladium-catalysed Catellani reaction in biomass-derived \u03b3-valerolactone\n\nPaper sections:\nIntroduction\nIn recent years, the direct C-H functionalization of arenes has emerged as a particularly attractive alternative to classical cross-coupling approaches, allowing for late-stage diversifications without the need of prefunctionalization steps. 1 Typically, directing groups are required for achieving site-selectivity in intermolecular transformations, mostly occurring at the ortho-position. The Catellani reaction represents an alternative strategy in which the palladium-catalysed C-H orthofunctionalization of aryl iodides is mediated by norbornene, which allows for subsequent ipso-substitution. In the original report by Catellani and coworkers the dialkylation of the aryl iodide in the two ortho-positions was followed by an ipso-vinylation through a Mizoroki-Heck-type process. 2 Several modifications to this reaction have subsequently been devised, allowing for different functionalizations to occur both on the ortho-as well as on the ipso-position. The most synthetically useful approaches towards the ipso-functionalization, apart from the Mizoroki-Heck-type alkenylation, include arylations through a Suzuki-Miyaura-type reaction, the alkynylation through a Sonogashira-type process and the hydrogenolysis of the aryl-palladium intermediate. 3 Thus far, the vast majority of C-H functionalization reactions have relied on homogeneous transition metal catalysis. Only recently the attention has shifted to the use of versatile heterogeneous catalysts for C-H activation chemistry. 4 However, to the best of our knowledge, examples of heterogeneous metal-catalysed Catellani reactions have as of yet proven elusive. It is particularly noteworthy that the use of heterogeneous catalysts offers great advantages as compared to homogeneous catalysts, especially in terms of recoverability of the catalysts, ease of purification and minimization of metal contamination.
Thus far, the Catellani reaction has largely been conducted in polar aprotic solvents, such as DMF, DMA or acetonitrile. These solvents, particularly DMF and DMA, present major issues related to their toxicity, and their substitution is highly desirable, especially for large-scale applications. 5 Acetonitrile is typically considered the \"greenest\" option among polar aprotic solvents. 6 However, this actually represents a rather poor alternative due to its volatility and toxicity. 7 \u03b3-Valerolactone (GVL), is a renewable biomass-derived chemical featuring high polarity, high boiling point, and good stability towards bases and acids. Only few applications employing GVL as reaction media have been disclosed. 8 Recently, we have reported for the first time that GVL can be used as an environmentally-benign alternative to common toxic polar aprotic solvents. 8i-k In some cases we have also observed that the use of GVL in combination with a heterogeneous catalyst lead to lower product contamination by the metal, compared to the same reaction performed in common polar aprotic solvents. 8i-k This is particularly relevant since metal contamination represent a major issue in the synthesis of pharmaceutical compounds. 9,10 In this article we report the first example of a Catellani reaction catalysed by a heterogeneous palladium species. The reaction is performed in a sustainable reaction media (GVL) and the optimal catalyst can be easily recovered and reused for consecutive reaction runs. Experimental mechanistic investigations were also conducted in order to clarify the nature of the catalytically active species.
\n\nResults and discussion\nAt the outset of our studies, we tested representative heterogeneous palladium catalysts in the Catellani reaction with methyl 2-iodobenzoate (1a) and methyl acrylate (2a), using K 2 CO 3 as the base and GVL as the medium (Table 1). 11 Commercially available encapsulated Pd(OAc) 2 , 12 either with or without PPh 3 (Pd EnCat\u2122 30 and Pd EnCat\u2122 TPP30, respectively) performed with high efficacy, affording the expected product 3a in more than 90% yield (Table 1, entries 1 and 2). The simple Pd/C catalyst gave comparable results, with an isolated yield of 94% (Table 1, entry 3). The addition of 2.5 equivalents of PPh 3 , either soluble or immobilized on a polystyrene support, led to a slight decrease in catalytic activity, with the product being obtained in 82-87% yield (Table 1, entries 4 and 5). Also commercially available Pd/Al 2 O 3 gave excellent results, providing the expected product in 95% yield (Table 1, entry 6). DMF, NMP, and MeCN were also tested as representative aprotic reaction media (Table 1, entries 7-9). While in the case of DMF satisfactory results were obtained, the use of NMP and MeCN led to poor conversion of the substrate 1a.
The effect of different basesboth organic and inorganicon the reaction was also investigated, with K 2 CO 3 giving the best results (see ESI \u2020).
Next, we explored the scope of the reaction between methyl 2-iodobenzoate (1a) and several olefins 2. We chose to conduct all reactions with Pd EnCat\u2122 30 as well as Pd/Al 2 O 3 , in order to investigate possible differences in reactivity between these two rather diverse heterogeneous catalysts. Generally, both catalysts performed well, providing the expected products in moderate to very good yields. In several cases Pd EnCat\u2122 30 gave slightly better results in terms of yields than Pd/Al 2 O 3 . \u03b1,\u03b2-Unsaturated esters and ketones (2a-c) were efficiently converted to the product by either of the two catalytic systems in yields ranging from 60% to 95% (Tables 2 and 3, entries 1-3). Acrylonitrile (2d) furnished good results in the reaction catalysed by Pd EnCat\u2122 30 (Table 2, entry 4), while much lower yield was obtained using Pd/Al 2 O 3 , which also needed longer reaction times (Table 3, entry 4).
Vinyl alkyl ethers (2e-f ) proved to be more challenging, and the efficacy was strongly dependent on the nature of the catalyst (Tables 2 and 3, entries 5 and 6).
Moreover, the reaction conducted on vinyl ethyl ether (2f ) with Pd EnCat\u2122 30 delivered the formyl-substituted product through a Domino Catellani reaction along with hydrolysis and keto/enol tautomerization. Styrene (2g) and para-substituted styrenes (2h-i) reacted efficiently with both catalysts (Tables 2 and 3, entries 7-9).
Interestingly, in both the reactions performed with the two catalysts, the chlorine functionality was well tolerated (Tables 2 and 3, entry 9), which should prove instrumental for further late-stage diversifications.
1,1-Disubstituted olefins were also subjected to the optimized reaction conditions with either Pd EnCat\u2122 30 or Pd/Al 2 O 3 as the catalysts (Tables 2 and 3, entries 10 and 11).
Their reactivity was in line with that observed for the monosubstituted olefins, with yields ranging from 41% to 68%. However, due to the presence of the methyl group on the substrate, the \u03b2-elimination step of the final Mizoroki-Heck-type reaction could occur in two positions, thus generating two isomeric products (3 and 4). As to the substitution pattern on the aryl iodides 1, the optimized palladium catalyst also enabled the synthesis of products 3l-3o (Scheme 1). The coupling of the Catellani reaction with a terminal hydrogenolysis step provides step-economical access to metadifunctionalized aromatic species. 3,13 We tested the applicability of this strategy under the optimized reaction conditions with Pd/Al 2 O 3 as the catalyst and benzyl alcohol as hydride donor (Scheme 2). The reaction proceeded efficiently, affording the expected coupling product 5 in high yield.
A major issue associated with transition metal catalysis, and in particular with palladium chemistry, is the nature of the catalytic active species. Indeed, it frequently was noted that operationally heterogeneous reactions actually occur through the catalysis of soluble leached metal species or, vice versa, that operationally homogeneous reactions were catalysed by in situ formed insoluble metal particles. 14 This problem is also of key relevance for C-H functionalization reactions. 4 It is worth considering that the actual nature of the catalyst is not only important for mechanistic reasons, but also has practical implications, since it finally controls the possibility to reuse the recovered catalyst and the metal contamination of the products. Unfortunately, assessing the nature of the catalytic active species (homogeneous vs. heterogeneous) is not a simple task. Several experiments have been proposed but none of them is able to give conclusive evidence about the mechanism. Instead, it is necessary to rely on multiple experiments in order to possibly obtain sufficient support to one of the mechanistic scenarios. 14 For these reasons, we decided to investigate the nature of the catalytically active species through various approaches, for both the reactions catalysed by Pd EnCat\u2122 30 and by Pd/ Al 2 O 3 . First, we performed a hot-filtration test by removing the solid catalyst one hour after the beginning of the representative reaction between 1a and 2a, and allowing the filtrate to stir for 3 days at 105 \u00b0C. Interestingly, the two catalysts led to quite different results. Thus, while Pd/Al 2 O 3 gave a very low conversion (7%), Pd EnCat\u2122 30 furnished 3a in 37% conversion. Second, for the same reaction we performed a mercurypoisoning test for both catalysts. Again, the two catalysts behaved differently. In fact, while the addition of Hg(0) completely hampered the catalytic activity of Pd/Al 2 O 3 with only 4% conversion after 20 hours, the reaction with Pd EnCat\u2122 30 gave 46% conversion under otherwise identical reaction conditions (see ESI \u2020). These results suggest that leached palladium species might play a key role in the reaction catalysed by Pd EnCat\u2122 30, but not in the reaction with Pd/Al 2 O 3 . 15 Third, we measured the amount of palladium leached into the crude product by inductively coupled plasma optical emission spectrometry (ICP-OES), for both catalysts, before and after aqueous work-up (Table 4). The amount of palladium leached from Pd/Al 2 O 3 was very low, even before aqueous work-up (\u223c2 ppm). However, the extent of metal leaching from Pd EnCat\u2122 30 is relatively high (52.4 and 10.5 ppm before and after aqueous work-up, respectively), and in line with previous findings 15 and with our hot-filtration and Hg-poisoning tests.
Overall, these results suggest that the two tested catalysts exert their catalytic activity in different ways. While Pd EnCat\u2122 30 is proposed to catalyse the reaction by releasing homo- geneous soluble palladium species, the C-H activation catalysed by Pd/Al 2 O 3 is either genuinely heterogeneous or may proceed through a \"release and catch\" mechanism. 16 From sustainability and chemical efficiency point of views, it is mostly important that the amount of palladium leached into the product is very low and that the solid catalyst can be efficiently reused. Therefore we tested the recyclability of Pd/ Al 2 O 3 in the reaction between 1a and 2a in GVL, by recovering the catalyst by simple filtration. The catalyst fully retained its activity for at least three reaction runs, constantly giving full conversion to the products. Thus, the reaction of substrates 1a and 2a was repeated for four consecutive runs giving the desired product 3a constantly in 93-95% yield (Fig. 1).
\n\nConclusions\nIn conclusion, we have developed the first Catellani reaction catalysed by a solid palladium catalyst. The reaction proceeded efficiently on a variety of alkenes in the renewable biomassderived medium GVL. The process could also be merged with a terminal hydrogenolysis, which gave step-economical access to valuable meta-difunctionalized 17 arenes. The nature of the catalytically active species was investigated and provided support for the versatile Pd/Al 2 O 3 catalyst to operate in a heterogeneous fashion. Importantly, the catalyst could be efficiently recovered and reused, featuring a very low metal leaching. Studies on the use of other economically attractive organic electrophiles are currently ongoing in our laboratories and will be reported in due course.
\n\nTypical procedure for the Catellani reaction\nTo a 4 mL vial containing the palladium catalyst (0.00825 mmol, 5 mol%), the base (0.340 mmol), and 2-norbornene (12 mg, 0.127 mmol) was added a GVL solution (3.75 mL) of the aryl iodide 1 (0.33 mmol) and the terminal olefin 2 (0.195 mmol). The resulting mixture was stirred at 105 \u00b0C.
The solids were then separated from the solution by vacuum filtration and rinsed with cyclopentyl methyl ether. The organic layer was washed with water and dried over anhydrous Na 2 SO 4 . The products were isolated by flash column chromatography using a 4 : 1 mixture of petroleum ether and ethyl acetate as the eluent.
\n\nProcedure for catalyst recovery and recycling\nAfter stirring at 105 \u00b0C for 24 h, the reaction mixture was centrifuged and the solvent was decanted. The catalyst was washed, first with water (0.2 mL) and GVL (3.0 mL), then with GVL (3.8 mL). New substrates (1a and 2a), reagents and solvent were added and left for 24 h at 105 \u00b0C for the next run. In four consecutive reaction runs Pd/Al 2 O 3 consistently led to full conversion to the expected product in 24 h.
", "answer": "Herein, we report the unprecedented use of a heterogeneous palladium catalyst for the step-economical Catellani reaction. The substrate scope with encapsulated Pd(OAc) 2 (Pd EnCat\u2122 30) or Pd/Al 2 O 3 proved to be broad, while the renewable biomass-derived \u03b3-valerolactone (GVL) was identified as an effective reaction medium. Mechanistic studies highlighted the possible heterogeneous nature of the Pd/Al 2 O 3 catalyst, while showing that the reaction performed in the presence of Pd EnCat\u2122 30 is most likely catalysed by leached homogeneous palladium species. The heterogeneous Pd/Al 2 O 3 catalyst can be easily recovered at the end of the reaction and efficiently reused in consecutive reaction runs. \u2020 Electronic supplementary information (ESI) available: Experimental details, characterization data, and copies of NMR spectra of known (3a and 5) and new compounds (3b-3o, 3\u2032h, 4j, 4k).", "id": 562} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneonatal group b streptococcus ( gbs ) infection ranging from 0.5 to 2 per 1000 live birth is the result of vertical transmission to the infant during delivery in colonized mothers .\nattempts at identifying gbs colonized pregnant women near term by assessing the risk factors for gbs , failed to diagnose all cases .\nuniversal screening of all pregnant women for gbs at 3537 weeks of gestation is currently recommended by the centers for disease control and prevention ( cdc ) in the usa . \ndespite the variation in the adherence to cdc recommendations among different centers around the world , antimicrobial prophylaxis , offered to women colonized with gbs intrapartum ( after onset of labor or after rupture of membranes ) , lead to more than 70% reduction in early - onset gbs infection in neonates .\nhowever , due to the variation in the rate of gbs colonization during pregnancy , the emergence of resistant colonizing strains and the virulence potential of these strains , intrapartum screening of gbs genotypes along with their antimicrobial resistance profiles , and virulence encoding genes become desirable . \nfortunately , gbs resistance to penicillin has not been reported so far ; however , rare gbs clinical strains with reduced sensitivity for penicillin have been recorded . on the other hand , early studies on gbs\nisolates from pregnant women , showed antimicrobial resistance as high as 18% , 8% , and > 80% for erythromycin , clindamycin , and tetracycline respectively . \nthe severity of neonatal disease in gbs infections could be determined mostly by a number of virulence factors encoded among others by the cps gene cluster coding for the capsule , the scpb gene coding for surface enzyme scpb ( a c5a peptidase ) which causes impairing of neutrophil recruitment and binds fibronectin to promote bacterial invasion of epithelial cells , the bca gene coding for alpha - c protein , a surface protein that helps the bacteria to enter the host cells , the lmb gene coding for lmb ( laminine - binding protein ) , a surface protein that plays a role in invasion of damaged epithelium , the cyle gene coding for -hemolysin , a toxin that plays a role in tissue injury and systemic spread of the bacteria and contributes to meningitis , and the rib gene encoding the surface rib protein mostly present in invasive strains .\nother virulence factors involved in the process of gbs pathogenesis include beta - c protein which is encoded by bac gene .\nbeta - c protein function is comprised of interaction with iga - fc portion causing the inhibition of phagocytosis and binding factor - h to maintain its role in inhibiting the complement activation via the alternative pathway .\nother important virulence factors of gbs are the fibrinogen - binding proteins : fbsa and fbsb .\nit protects the pathogen from opsonophagocytosis , and promotes its adherence to epithelial cells and to the human brain microvascular endothelial cells ( hbmec ) thus helping it to cross the blood brain barrier and developing meningitis [ 18 , 19 ] .\nfbsb protein , encoded by fbsb gene , is also a surface protein that helps in gbs invasion of the epithelial cells .\nfinally , cell - surface - associated protein ( cspa ) is a surface protein encoded by cspa gene .\nit is involved in maintaining the pathogen survival in the host by escaping the immune system . in this study , genotypes were correlated to some of the virulence genes and the antimicrobial susceptibility profiles .\nthis information is useful to identify particular gbs strains with high virulence potential , with resistance to routinely administered antimicrobial agents , and possibly linked to particular geographical areas .\nseventy six gbs isolates were cultured from specimen taken from the vaginas of pregnant women between 35 and 37 weeks of gestation , attending private clinics in two tertiary care centers in beirut , lebanon , between october 2007 and july 2008 . the first center ( a ) is located in the western part of the urban city of beirut , and the second one ( b ) in the eastern part of beirut .\nthese two hospitals serve two different populations , in the sense that patients attending the hospitals come from 2 different geographical areas , with very minimal intermingling between them . however , the local health care systems of the two areas are similar , and patients have similar antibiotics consumption habits .\nthe 76 gbs isolates consisted of 47 ( 61.8% ) isolates obtained from the first tertiary care center and 29 ( 38.2% ) isolates obtained from the second tertiary care center .\nisolates were identified using conventional methods on the basis of colonial morphology , gram staining , haemolysis , and latex agglutination test with specific antisera using the slidex strepto plus ( biomerieux , marcy l'etoile ; france ) .\nantimicrobial susceptibility testing was performed by the disk - diffusion ( kirby - bauer ) method on mueller - hinton agar ( difco laboratories , detroit , michigan ) supplemented with 5% sheep blood , using suspensions of 0.5 macfarland from fresh bacterial cultures .\nthe test was done using the following antimicrobial agents : penicillin , cefepime , ceftriaxone , chloramphenicol , clindamycin , erythromycin , levofloxacin , and tetracycline .\ndna was extracted from all isolates using the illustra bacteria genomicprep mini spin kit ( ge healthcare uk ltd , buckinghamshire , england ) according to the manufacturer 's instructions .\ntotal dna of the 76 gbs isolates was used to amplify five virulence factors encoding genes : cyle , rib , lmb , bca , and scpb by pcr using specific primers .\nstandard pcr conditions were used to amplify cyle , lmb , and scpb , rib , and bca gene . \namplicons were subjected to electrophoresis on 2% agarose ( sigma ) gels in 1 tris - borate - edta buffer ph 8.3 ( tris base 0.089 m , boric acid 0.089 m , and edta 0.002 m ) at 120 v for 45 minutes . \nagarose gels were stained with ethidium bromide ( sigma ) and photographed using a uv - transilluminator and an olympus digital camera with digi - doc it program .\ngenotyping using random amplified polymorphic dna ( rapd ) analysis was performed on all the isolates to determine strain diversity .\nrapd was performed with the ready - to - go rapd analysis beads kit ( ge healthcare uk ltd , buckinghamshire , england ) and the gbs 2 primer , using sprint , thermo electric thermal cycler .\nantimicrobial susceptibility testing showed the following : all gbs isolates were susceptible to penicillin g , cefepime , ceftriaxone , and levofloxacin .\nthe following percentages of isolates , 4% , 11.8% , 15.8% , and 86.8% , were resistant to chloramphenicol ( chl ) , clindamycin ( cli ) , erythromycin ( ery ) , and tetracycline ( tet ) respectively .\nsix antimicrobial resistance ( ar ) profiles of isolates were detected : a ( resistant to cli , ery , chl , and tet ; 4.0% ) , b ( resistant to cli , ery , and tet ; 6.6% ) , c ( resistant to cli and tet ; 1.3% ) , d ( resistant to ery and tet ; 5.3% ) , e ( resistant to only tet ; 69.7% ) , and f ( susceptible to all ; 13.2% ) .\ngenotyping of all the isolates detected seven gbs clusters i , ii , iii , iv , v , vi , and vii with the following prevalence percentages : 18.4% , 13.2% , 19.4% , 7.9% , 11.8% , 11.8% , and 17.1% , respectively . a dendrogram of the seven clusters of genotypes\nthe most common cluster was iii ( 19.7% ) and the least prevalent was iv ( 7.9% ) .\nthe data show a prevalence of certain genotype clusters in both tertiary care centers while other genotype clusters were merely confined to a particular tertiary center ( table 2 ) . similarly , certain ar profiles were prevalent in both centers , whereas others were restricted to one center .\npcr detection of the virulence genes showed that cyle , lmb , scpb , bca , and rib genes were positive in 99% , 96.1% , 94.7% , 56.6% , and 33% of the gbs isolates respectively .\nthere was a wide prevalence of the cyle , lmb , and scpb genes among the total isolates , and hence all 3 genes were evenly distributed among the genotype clusters .\ntable 3 shows the prevalence of bca and rib genes among the gbs genotype clusters .\nsixty eight isolates out of 76 ( 89.5% ) have either the bca or the rib gene and 8 isolates out of 76 ( 10.5% ) have neither bca nor rib detected .\nneonatal gbs infection is a serious complication of the vertical transmission of the bacteria , from the mother to the newborn , at the time of vaginal delivery .\nthis is why universal screening for gbs vaginal colonization in pregnant women near term is recommended . \nfortunately , gbs resistant to penicillin has not been reported all around the world , and the drug of choice , in treating the infection , is still penicillin [ 7 , 9 ] .\nhowever , the problem arises in cases , allergic to penicillin , where alternate antimicrobial agents such as cli and ery are commonly administered .\nhowever , de azavedo et al . found that 18% , 8% , and > 80% of gbs isolates in pregnant women were resistant to ery , cli , and tet . in our study ,\n11.8% , 15.8% , and 86.8% of the gbs isolates , were resistant to ery , cli , and tet respectively , indicating percentages similar to previous studies .\nthe prevalence of this relatively high ar percentages , leads to the recommendation of requesting a sensitivity antibiogram for gbs cultured from women allergic to penicillin . \ngenotyping of all the gbs isolates , utilizing rapd analysis determined a total of 7 genotype clusters .\nthe most common was genotype cluster iii ( 19.7% ) and the least common was iv found in 7.9% of all isolates . \na correlation between ar and genotype clusters , showed an association between them ( table 1 ) .\nresistance to chl was restricted to genotype clusters v , vi , and vii , whereas resistance to both cli and ery was found only in genotype clusters i , ii , and vii .\nall the gbs isolates resistant to cli are also resistant to ery , indicating a correlating pattern of resistance amongst the genes responsible for this phenotype .\nthis can be expected since cli resistance in gbs is nearly always based on the presence of an ermb gene conferring resistance to macrolides , lincosamides , and streptogramin b . \nan important finding in this study was the correlation between the prevalence of particular genotype clusters with certain ar profiles in a given medical center .\nthis observation denotes that high prevalence of certain genotype clusters resistant to certain antimicrobial agents in a particular medical center entails the practice of caution by extrapolating the ar findings from one medical center to others . \nanother observation is that bca and rib genes were not present concomitantly in the same genome .\nrib protein encoded by the rib gene shares several properties with -c protein encoded by bca gene .\nboth proteins are resistant to trypsin digestion and belong to the same family of bacterial surface proteins with repetitive structures showing a 47% identity , their n - terminal sequences are related and are 61% identical to each other .\nfurther investigations are still needed to be performed in order to discover the functional relationship between bca and rib to determine if they have homologous functions .", "answer": "the antimicrobial \n susceptibility profiles of 76 \n streptococcus agalactiae ( group \n b streptococci [ gbs ] ) isolates from vaginal \n specimens of pregnant women near term were \n correlated to their genotypes generated by \n random amplified polymorphic dna analysis and \n their virulence factors encoding genes \n cyle , lmb , scpb , rib , and bca \n by pcr . based on the distribution of the \n susceptibility patterns , \n six profiles were \n generated . \n rapd analysis detected 7 clusters of \n genotypes . \n the cyle gene was \n present in 99% of the isolates , the \n lmb in 96% , \n scpb in 94.7% , \n rib in 33% , and \n bca in 56.5% of isolates . \n \n the isolates demonstrated a significant \n correlation between antimicrobial resistance and \n genotype clusters denoting the distribution of \n particular clones with different antimicrobial \n resistance profiles , entailing the practice of \n caution in therapeutic options . \n all virulence \n factors encoding genes were detected in all \n seven genotypic clusters with \n rib and bca \n not coexisting in the same \n genome .", "id": 563} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmegalourethra is a rare congenital mesenchymal anomaly of the male anterior urethra characterized by a nonobstructive dilatation of the penile urethra .\nnesbitt in 1955 defined it as a congenital dilatation of penile urethra without distal obstruction .\ndorairajan classified congenital megalourethra into two types based on findings of urethrography . the more common scaphoid type with a deficiency of the corpus spongiosum is seen as bulging of ventral urethra .\nthe fusifrom type with deficiency of both corpus spongiosum and cavernosum is seen as circumferential expansion of urethra .\na 6-month - old male child presented with dribbling of urine with a noticeable swelling of undersurface of penis which increased during the act of micturition . on examination a scaphoid\nswelling of size 4 3 cm was seen on the ventral aspect of shaft of penis which ballooned out during micturition .\nultrasound of abdomen and pelvis showed normal kidneys and bladder with no post void residue .\nretrograde urethrogram showed scaphoid dilatation of ventral aspect of distal and mid penile urethra confirming the diagnosis of congenital megalourethra [ figure 1b ] .\ncystourethroscopy showed wide saccular dilatation of penile urethra about 1 cm from external urethral meatus .\nretrograde urethrogram showing ventral saccular dilatation of urethra a reduction urethroplasty was done through circumcoronal penile incision .\nafter degloving the penis scaphoid dilatation of ventral aspect of penile urethra was noted [ figure 2 ] .\nthe dilated urethra was incised in ventral midline and the redundant urethra with deficient corpus spongiosum was excised and the urethra was reconstructed over 6 fr infant feeding tube using 5 - 0 pds suture .\npostoperative recovery was uneventful . on removal of the catheter after 2 weeks child voided normally without any penile swelling .\nregular follow - up at 1 year showed no recurrence of penile swelling with normal voiding pattern and sonologically normal bladder and upper tracts .\nthe most commonly held theories propose a defect in the migration , differentiation , or development of the mesenchymal tissues of the phallus .\nanother assumption is that delayed or deficient canalization of the glandular urethra may be associated with maldevelopment of the corpus spongiosum and corpora cavernosae . due to the poor development of erectile tissue which normally provides support\ntwo types of megalourethra are described depending upon the extent of associated embryonic maldevelopment of erectile tissue .\njones et al . , in a review identified associated anomalies in 66 of 78 reported cases of megalourethra . in this review ,\nassociated congenital anomalies are seen in 80% of scaphoid type and 100% of fusiform type .\nthe commonly described genitourinary anomalies include renal dysplasia - hypoplasia , hydronephrosis , hydroureter , vesicoureteric reflux , prune - belly syndrome , urethral duplication , megacystis , hypospadias , posterior urethral valves , and undescended testes .\nother system anomalies including vater ( vertebral , anal atresia , trachea - esophageal fistula , and renal anomalies ) and vacteryl ( vertebral , anal atresia , cardiac , trachea - esophageal fistula , renal , and limb deformities ) are described . in view of associated anomalies , the workup of megalourethra should include renal function tests and imaging of upper and lower urinary tracts\nurethral anomalies mimicking megalourethra like urethral atresia , a web , duplication , and a diverticulum are considered in the differential diagnosis .\nprenatally diagnosed megalourethra has to be thoroughly evaluated for associated congenital anomalies and followed up serially by ultrasound for amniotic fluid index , urinary bladder volume , and upper tract dilatation .\ntermination of pregnancy may be advised in cases with other severe congenital anomalies and renal impairment . in some milder forms of megalourethra spontaneous resolution has been observed in fetuses at 19 - 34 weeks gestation .\nthe treatment of megalourethra may be one stage or two stage urethroplasty depending on the age of presentation and general condition of the patient . for scaphoid type , nesbitt described a longitudinal reduction urethroplasty .\nheaton and colleagues described a technique of urethral plication for some cases of scaphoid megalourethra .\nthe management of fusiform type is complicated ranging from sex reassignment to major phallic reconstruction .\nlong - term follow - up is required in these patients to see for the erectile function and fertility potential .\nmanagement has to be individualized depending on type and the presence of associated congenital anomalies . in isolated scaphoid type of megalourethra reduction", "answer": "megalourethra is a rare congenital disorder of anterior urethra and erectile tissue of penis . \n it mainly appears in two types a milder scaphoid type and severe fusiform type . \n fusiform type is commonly associated with congenital anomalies of various systems of the body . \n isolated megalourethra without other congenital anomalies is extremely rare . \n we report one such case which was detected postnatally and successfully treated by reduction urethroplasty .", "id": 564} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSuzuki-Miyaura cross-coupling towards 4-amino biphenyl intermediates\n\nPaper sections:\nIntroduction\nThe synthesis of biaryl units (mainly amino biphenyls) has attracted a lot of attention and efforts from many research groups, both in academy and industry, due to their importance as key intermediates in the synthesis of pharmaceuticals, agrochemicals, natural products, etc.
The Suzuki-Miyuara cross-coupling reaction is an extremely useful approach for the construction of biaryl units as the reaction is much less sensitive to moisture and oxygen in comparison to other cross-coupling reactions and it allows very low metal catalyst loadings, which has a significant impact on price reduction on industrial scale.
While the Suzuki-Miyaura cross-coupling usually works well with aryl iodides, bromides, and triflates when reacting with boronic acids, the reaction is usually less efficient with aryl chlorides. An even larger challenge is reacting electron-rich aryl chlorides such as chloroanilines, 1,2 which are the desired starting materials towards aminobiphenyl species, as they are much cheaper than the respective aryl bromides. For this reason, few examples in the literature show successful reactions with chloroanilines and these usually with unsubstituted boronic acids. 3 An additional challenge is to perform these reactions with phenylboronic acids substituted by more than two halogens. Barder et al. have presented an example of Suzuki-Miyaura cross coupling of 4-chloroaniline with 2,4-difluorophenylboronic acid with a high yield of 96% in the presence of 1 mol% of \uf0a8 These authors contributed equally. * Corresponding author, e-mail: rafal.lisiak@selvita.com Pd(OAc)2 catalyst and 2 mol% of a bulky phosphine ligand (SPhos). However, when attempting the same reaction with 2,4,6-trifluorophenylboronic acid, it did not proceed efficiently. 4 Here we report an attempt to perform a Suzuki-Miyaura cross coupling reaction of 4-chloroaniline with 3,4,5-trifluoroboronic acid in a similar catalytic system.
In this case, we were able to reach a somewhat low conversion (19%) under these conditions. We managed to slightly improve the conversion to 42% by altering the reaction conditions, but still obtained relatively low yields, which is in line with the significant challenge and unpredictability of reacting chloroanilines with multisubstituted phenylboronic acids in the presence of SPhos and similar ligands.
\n\nExperimental procedures Example 1:\n26 mg of Pd(OAc)2 (0.12 mmol, 0.01 eq.) and 97 mg of SPhos (0.24 mmol, 0.02 eq.) were dissolved in 15 ml of toluene and 1.5 ml of H2O under nitrogen in a pressure tube, and stirred for 15 min at RT to form a catalyst solution. Then, 4.99 g of K3PO4 (0.0235 mol, 2 eq), 3.1 g of 3,4,5-trifluorophenylboronic acid (0.0176 mol, 1.5 eq) and 1.5 g of 4-chloroaniline (0.01176 mol, 1 eq) were added to the catalyst solution. The reaction mixture was heated to 100\u00b0 C for 15 h. The reaction mixture was cooled to 25 \u00b0C, and the layers were separated. The organic phase was analyzed by GC area %: 19.9 % calculated conversion towards the desired product (3,4,5-trifluoro-4'-aminobiphenyl).
\n\nExample 2:\n6 mg of palladium chloride (0.03 mmol, 0.1 mol%) and 28 mg of SPhos (0.06 mmol, 0.2 mol%) were dissolved in 20 ml of DMAc -water solution (1:1) at 25\u00b0C, under nitrogen, and stirred for 15 min to form a catalyst solution. Then, 7 g of potassium carbonate (0.050 mol, 1.5eq), 6 g of 3,4,5trifluorophenylboronic acid (0.034 mol, 1 eq) and 4.35 g of 4-chloroaniline (0.034 mol, 1 eq) were added to the catalyst solution. 25 ml of additional water -DMAc solution (1:1) were used to transfer the starting materials completely. The reactor was heated to 10 0\u00b0C inner temperature for 5 h. The reactor was cooled to 25 \u00b0C and the layers were separated. The organic phase was analyzed by GC area %: 42 % calculated conversion towards the desired product (3,4,5-trifluoro-4'-aminobiphenyl).
", "answer": "The preparation of biphenyl derivatives bearing amino groups via direct cross-coupling reaction is being widely explored due to its importance for many branches of the chemical industry. One of the necessary components for such a transformation are halogenated arenes. In order to make the process more economical, we focus on inexpensive and easily available aryl chlorides which usually are not considered reagents of choice for catalytic couplings. In the following short communication, we report the results of the coupling of relatively unreactive chloroaniline with a fluorinated phenylboronic acid leading to the corresponding aminobiphenyl.", "id": 565} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnontyphoidal salmonella species are important food borne pathogens and acute gastroenteritis is the most common clinical manifestation accounting for about 70% of cases .\nsplenic abscess is a very rare complication of nontyphoidal salmonella infections since the presence of antibiotics . here\na 63-year - old woman from eastern part of turkey was admitted with the complaint of back pain , vomiting and nausea since 20 days .\nlaboratory findings were as follows : white blood cell ( wbc ) count was 14670/mm ( 88.9% polymorphonuclear cells ) , haemoglobin 9.5 g / dl , platelet count 183000/mm , erythrocyte sedimentation rate 76 mm / h , and c - reactive protein ( crp ) 58 mg / dl ( normal value < 5 mg / l ) .\nan abdominal ultrasound revealed a hypoechogenic cystic structure with a diameter of 6172 mm in the upper part of the spleen with calcifications ( figure 1 ) .\nsalmonella enteritidis was yielded from culture of the samples of the abscess obtained during the operation .\nit was sensitive to ampicillin , cotrimoxazole , cephalosporins of third generation , and ciprofloxacin . \n\nafter isolation of the s. enteritidis from abscess , the patient was questioned in detail , it was learned that the patient had diarrhoea and fever existed 2 days and recovered without antibiotic treatment one month ago .\nthe usual clinical presentation of nontyphoidal salmonella infection is self - limited gastroenteritis , however bacteraemia and focal extraintestinal infections may occur .\nrisk of bacteraemia and focal extraintestinal infections are high in individuals with comorbidities such as malignancy , human immunodeficiency virus ( hiv ) , diabetes mellitus , and patients receiving immunosuppressive therapy .\ninvasive nontyphoidal salmonellae disease is a major cause of mortality in african children and hiv - infected african adults .\nany tissue or organ may be seeded hematogenously by nontyphoidal salmonella and may form a local infection , become obvious months or even years after the initial bacteraemia producing characteristic clinical syndromes .\nsome serovars of salmonella show a higher tendency for causing bacteraemia and these serovars differ in different countries . non - typhoidal salmonella serovars s. typhimurium and s. enteritidis are cause of invasive disease in industrialized countries , also they are predominant in african region . \n\ns. enteritidis had the highest blood invasiveness among non - typhoidal salmonella species in malaysia . our patient had diabetes mellitus and probably s. enteritidis bacteraemia occurred during the course of diarrhoea one month ago which lead to bacterial seeding in the spleen .\nantibiotic treatment for patients with mild to moderate gastroenteritis due to non - typhoidal salmonella is not indicated in healthy adults .\nhowever antimicrobial therapy should be initiated for patients who are severely ill and for patients with risk factors for extraintestinal spread of infection .\nthe symptoms of splenic abscess are usually nonspecific the most frequent symptoms and signs are fever , abdominal pain and tenderness over left upper quadrant , splenomegaly , leucocytosis , and left lower chest abnormalities .\nour patient had back pain , vomiting , nausea and leucocytosis which were not specific for splenic abscess .\ncomputed tomography remains the gold standard and the most sensitive tool for the definitive diagnosis of splenic abscess .\nultrasonography has 76% , ct has 96% sensitivity for the detection of abdominal masses . in our patient ,\ndiagnosis was confirmed with ct . at present , splenectomy is the gold standard for treatment while ultrasound- or ct - assisted percutaneous drainage and antimicrobial therapy can be considered as therapeutic alternatives especially in the presence of an isolated abscess .\nwe preferred splenectomy for treatment as the causative microorganism was not known initially . in conclusion , although non - typhoidal salmonella gastroenteritis is rarely resulted with splenic abscess , patients with comorbities are at increased risk .", "answer": "splenic abscess is a very rare complication of non - typhoidal salmonella infections . \n we report a case of splenic abscess caused by salmonella enteritidis . \n the patient is a 63-year - old woman with diabetes mellitus and underwent splenectomy . \n this case suggests that the patients with comorbities are at increased risk for invasive infections in non - typhoidal salmonella infections .", "id": 566} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nureteral avulsion is conventionally defined as injuries of the ureter caused by blunt ( non - penetrating ) trauma with acute deceleration or acceleration movement mechanism due to motor vehicle accidents . with the invention of endourology tools ,\nureteral avulsion can also occur as a result of stretching in the weakest point of the ureter .\nureteral avulsion and perforation during ureteroscopy are the most common cause of iatrogenic ureteral injuries .\nthe rate of ureteral injury dropped to 7% in 1990 due to increased surgical experience and development of more advanced uertroscopy tools .\nthe incidence of ureteral perforation has been reported in 1.5% of such procedures of which 0.2% have required surgery . in spite of the prevalent use of ureteroscopy in the treatment of ureteral stones and replacement of open surgical procedures with ureteroscopic procedures , the rate major and severe complications such as avulsion and perforation commands attention [ 6 , 7 ] .\nureteral avulsion from the pelvis can be managed by ureteral reimplantation , transureteroureterostomy and ureteroneocystostomy [ 810 ] .\nrenal autotransplantation can be an appropriate whenever a considerable length of the ureter is lost or a previous surgery has failed .\nmeanwhile , sometimes after such procedure renal impairment is encountered . in the present case ,\nwe report a successful autotransplantatioin in a patient who underwent urgent operation following avulsion of the ureter at a distance of 4 cm from the pelvis .\nsurgeons should be aware of possible complications attributed to transureteral lithotripsy ( tul ) and their knowledge and expertize in managing such complications .\nthe patient was a 51-year - old lady with left flank colicky pain associated with nauseas and vomiting for a month .\nstudy of kub ( kidney , ureter , and bladder x - ray ) and non - contrast abdominopelvic spiral ct scan images revealed a 1-cm proximal left ureteral stone ( fig .\n1 ) . accordingly the patient was selected to undergo tul and ureteral stenting . \n figure 1:abdominopelvic spiral ct scan of the patient before surgery .\nabdominopelvic spiral ct scan of the patient before surgery . due to a narrow ureteral lumen proceeding with the procedure seemed impossible and we decided to terminate the surgery . while taking out the ureteroscope we noticed avulsion of the ureter at a point approximately 4 cm from ureteropelvic junction .\nthe avulsed ureter was handing on the tip of the ureteroscope and the avulsed fragment came out along with the ureteroscope .\nafter thorough evaluation of various possible methods to approach the problem , the patient was brought to a left flank position from her original lithotomy position . with a left intercostal incision nephrectomy was done .\nsubsequently , the position of the patient was changed to supine and a gibson incision was made over the right lower quadrant of the abdomen .\nfollowing dissection of the iliac vessels , renal vessels were anastomosed to the iliac vessels ( renal artery to the internal iliac artery and renal vein to the external iliac vein ) . using the lich \ngiven the fact that only a short segment of the avulsed ureter ( 4 cm ) was left , we considered implantation of the ureter to the bladder .\na drainage tube was inserted to drain any possible bleeding from the operation site and then the surgical wound was closed .\nthe patient was discharged in a good general condition after 3 days and the drainage tube removed .\nan ultrasound imaging study of the genitourinary system 8 months into the patients follow up showed normal size , echo and cortical thickness in the operated kidney after renal autotransplantation . in follow up , 2 months after renal autotransplantation , the arterial and venous flow of the transplanted kidney were normal on color doppler ultrasound imaging ( figs . 2 and 3 ) .\nthe mean parenchymal arterial vascular resistance in the transplanted kidney was 0.63 which was in the normal range .\nthe height , anteroposterior diameter and cortical thickness of the transplanted kidney were 117.41 mm and 13 mm , respectively .\nthe values of urea and creatinine 3 months after transplantation were 26.4 and 1.09 , respectively .\nsize , echo and cortical thickness of the transplanted kidney were reported normal in the follow up ultrasound 8 months after autotransplantation ( fig .\nfigure 3:color doppler ultrasound of the transplanted kidney 2 months after surgery in the zoomed area of the image . \n\nfigure 4:gray - scale ultrasonography of the patient 's transplanted kidney 8 months after surgery .\ncolor doppler ultrasound of the transplanted kidney 2 months after surgery in the zoomed area of the image .\nureteroscopy is widely used for lithotripsy procedure and resection of malignant tumors , but this method may lead to urethral mucosal trauma , hematuria , ureteral stenosis , urinary tract infection and ureteral perforation . among all complications of ureteroscopic lithotripsy procedure ,\ncomplete avulsion of the proximal ureter is one of the most challenging that happens in 0.060.45% of the cases .\nit is evident that appropriate decision making and a timely surgical intervention can prevent the need for nephrectomy and possible complications in the future .\nin general , management of ureteral avulsion depends on the location of injury , the length of the traumatized ureter , time of diagnosis , patient 's age and general health .\nboari flap and psoas hitch techniques are used in proximal and distal injury of the ureter .\nfinally , in the absence of the previous conditions , autotransplantation can be done as a vital method .\nit is evident that such surgical procedures require substantial expertize among all healthcare providers , a patient in a suitable physical status and proper age , and an accurate and timely decision making .\nautotransplantation was done in our patient after quick evaluation and review of different options to repair a traumatized ureter and clinical evidences supported the accomplishment of a successful outcome .", "answer": "abstractthe patient was a 51-year - old lady with left flank colicky pain accompanied with nausea and vomiting for a month . \n transurethral lithotripsy and ureteral stent placement was considered for the patient . \n the patient had a narrow ureteral lumen and while bringing the ureteroscope out , ureteral avulsion occurred at a distance approximately 4 cm from ureteropelvic junction . after bringing the uretroscope out , \n the avulsed ureter was observed hanging at the tip of the ureteroscope . \n anastomosis of the ureter to the bladder was accomplished with lich \n gregoir technique . \n a drainage tube was inserted at the site of incision and the surgical wound closed . \n the patient was discharged with acceptable general condition after 3 days and the drainage tube removed . \n the ureteral stent was removed 4 weeks later by cystoscopy . \n an ultrasound imaging study of the genitourinary system 8 months into the patients follow up showed normal size , echo and cortical thickness in the operated kidney after renal autotransplantation .", "id": 567} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nobstructive sleep apnea ( osa ) is a common public health problem worldwide and it has been shown to be associated with an increased incidence of cardiovascular complications such as death , stroke , or myocardial infarction .\nthe 2014 american heart association / american stroke association guideline recommends that patients with stroke / transient ischemic disorder ( tia ) showed be worked up for osa . in this study , patients who had osa and stroke had an improved outcome with continuous positive airway pressure .\nextrapolating data from western population and implementing in the asian populations may not be possible as there are differences in genetic and anatomical factors .\nfor example , the cutoff point for obesity based on body mass index ( bmi ) criterion for western population is 30 kg / m meanwhile the bmi for asian population is 25 kg / m .\nit is also evident that there are differences in anatomical factors between asian and caucasian population such as retrognathia and oropharyngeal width which are main risk factors for osa .\nalternatively , the stop - bang questionnaire developed by chung et al . has been widely used as a sensitive screening tool for osa .\nthe stop - bang acronym stands for : snoring history , tired during the day , observed stop breathing while sleep , high blood pressure , bmi more than 35 kg / m , age more than 50 years , neck circumference more than 40 cm and male gender .\nthe authors recommended that if a patient had 3 or more criteria mentioned above , it is strongly suggestive for osa .\nhowever , the cut - off values of this questionnaire are based on the data from caucasians , therefore we hypothesized that to use it in asian population , some adjustments are needed .\nwe compared the clinical features in the stop - bang questionnaire between osa - induced hypertension patients and healthy control subjects .\nthe study was conducted in the faculty of medicine , khon kaen university ( thailand ) .\nthe study protocol was approved by the ethics committee for human research , khon kaen university .\nosa induced - hypertension patients were diagnosed by : i ) met the criteria of hypertension ; ii ) having average apnea - hypopnea index ( ahi ) by polysomnography more than or equal 5 times / hours and iii ) no evidence of other secondary hypertension .\nthe control subjects filled up the modified berlin questionnaire and epworth sleepiness scale less than 10 and defined as low risk for osa with low scores .\ndemographic data and clinical features of both osa - induced hypertension patients and healthy subjects were recorded and compared .\nthe clinical features included age , gender , bmi , neck circumference , mallampati classification , torus palatinus , and torus mandibularis .\nthe mallampati classification was defined by asking the subjects to protrude their tongue as much as possible and classified as class 1 to 4 .\nthe sample size of the study population was calculated by using the proportion comparison between osa and healthy subjects using winpepi program .\nthe proportion of osa was 0.35 and the healthy control was 0.07 with deviation of 5% , power of 90% , and missing data of 10% .\nthe sample size was calculated to be 102 subjects ( osa 34 subjects and healthy control 68 subjects ) . due to the incompleteness of the database of medical students ,\n120 healthy controls were selected by systematic sampling from the database ( total of 1174 medical students ) .\nbaseline and clinical characteristics of the participants in both groups were compared using descriptive statistics .\nunivariate logistic regression analyses were applied to calculate the crude odds ratios of individual variables for having osa .\nall clinically significant variables or p<0.20 by the univariate analyses were included in subsequent multivariate logistic regression analyses .\nanalytical results were presented as crude odds ratios ( or ) , adjusted or , and 95% confidence intervals ( ci ) .\nsignificant risk factors were calculated for the best cut - off points by the receiver operator characteristic curve ( roc curve ) .\ndata analyses were performed with stata software ( college station , tx , usa ) and spss software ( chicago , il , usa ) .\nin this study , 42 osa - induced hypertension patients and 82 control subjects who had a complete set of clinical data were included . all clinical features of both groups\nthe osa - induced hypertension patients were significantly older ( 59.5 vs 21.0 years ) , with higher proportion of males ( 64.3 vs 59.8% ) , more obese ( 78.6 vs 6.1% ) , higher incidence of mallampati class 3 or more ( 54.8 vs 24.4% ) , larger neck circumference ( 41.3 vs 32.0 cm ) , higher incidence of torus palatinus ( 26.6 vs 0% ) and of torus mandibularis ( 9.5 vs 0% ) . by multiple logistic regression analysis , only two factors bmi and neck circumference ,\nthe adjusted odds ratios for both factors were 1.49 ( 95% ci : 1.06 , 2.09 ) and 1.67 ( 95% ci : 1.11 , 2.51 ) , respectively . by the roc curve analyses ,\nthe best cut - off points for the bmi and the neck circumference were 24.5 kg / m ( figure 1a ) and 36 cm ( figure 1b ) .\nthe sensitivity and the specificity for bmi cut - off point were 97.2% and 91.4% , whereas those for the neck circumference were 94.7% and 82.9% .\nthe present results showed that the stop - bang questionnaire needed to adjust the cutoff values of the bmi and neck circumference suitable for thai population .\nsubjects should referred for polysomnography if positive at least 3 questions : s , snoring history ; t , tired during the day ; o , observed stop breathing while sleep ; h , high blood pressure ; b , bmi more than 25 kg / m ; a , age more than 50 years ; n , neck circumference more than 36 cm ; g , male gender ( modified from chung et al . ) . for\nthe criteria of obesity for asians , the cut - off of the bmi should lower from 35 kg / m to 24.5 or round up to 25 kg / m .\nthe cut - off of the neck circumference also should be lowered from 40 cm to 36 cm for asians .\nproposed the cutoff points of 24.1 kg / m for the bmi and 35.5 cm for the neck circumference for japanese population .\nusing stop - bang questionnaire is very suitable for thailand and other developing countries due to limited availability of polysomnography , the standard diagnostic tool for osa .\nthis low cost tool can select appropriate patients for referral to sleep center for further polysomnography .\nhealthy control subjects were not performed polysomnography to exclude osa . however , both the berlin questionnaire and the epworth sleepiness scale were used to exclude osa , which has a sensitivity and specificity of 0.86 , 0.95 and 0.49 , 0.80 , respectively .\neven though the age is a significant factor by univariate logistic regression , it was not included in the subsequent multivariate regression .\nthis is because the difference of age group composition between the osa and the healthy control subjects .\nfurther studies , therefore , are needed to confirm the results of this study and to identify the appropriate cut - off point using the age- and sex - matched controls . also , to increase their sensitivity and specificity , osa patients with other complications than hypertension should be included and compared . whether simple measurement of the neck circumference and the bmi calculation are sufficient to identify osa patients in routine practice by primary health care personnel including physicians , nurses and volunteers should be examined in further study .\nosa has been proved to be a contributing factor for major cardiovascular diseases ; stroke , hypertension , sudden death , and also coronary artery disease .\ntreatment of osa may reduce large economic burden from prevention of the morbidity and mortality from stroke and acute coronary syndrome . in conclusion ,\nthe appropriate cut - off points for the bmi and the neck circumference for stop - bang questionnaire were 25 kg / m and 36 cm for asian people .\nall hypertensive patients should have their bmi and neck circumference measured to detect the risk factors for osa .\npublic health campaign for osa screening is also needed to reduce morbidity and mortality from osa complications .", "answer": "obstructive sleep apnea ( osa ) is a common public health issue . if left untreated , osa may cause a large health economic burden from cardiovascular complications particularly stroke . \n the diagnosis of osa can be made by polysomnography , but its availability is limited in the developing countries in asia . \n stop - bang questionnaire is a good screening tool but may need some adjustment for asian population . \n stop - bang stands for : snoring history , tired during the day , observed stop breathing while sleep , high blood pressure , body mass index ( bmi ) more than 35 kg / m2 , age more than 50 years , neck circumference more than 40 cm and male gender . \n we compared clinical features in stop - bang questionnaire between 42 osa induced hypertension patients and 82 healthy control subjects in the faculty of medicine , khon kaen university , thailand . \n the best cutoff point for the bmi and the neck circumference were 24.5 kg / m2 and 36 cm , respectively . \n the sensitivity and specificity of the bmi cutoff point were 97.2% and 91.40 , while those of the neck circumference were 94.7% and 82.9% . in conclusion , the appropriate cutoff points of bmi and neck circumference for thai stop - bang questionnaire were 25 kg / m2 and 36 cm .", "id": 568} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiabetes mellitus may predispose individuals to invasive fungal infections ( ifi ) probably \n related to impaired functions of neutrophils , macrophages , cellular and humoral immunity , \n and iron metabolism ( 1 , 2 ) . children with type 1 diabetes ( t1d ) who present with ketoacidosis have \n increased susceptibility to infections partly due to the acidic environment that is ideal \n for certain pathogens including invasive fungi ( 1 , \n 3 ) .\nmajority of the ifis in children with poorly \n controlled t1d and ketoacidosis are caused by zygomycoses and are invariably fatal without \n aggressive management ( 4 ) .\nthe key to good outcome is \n fast and accurate diagnosis which is usually difficult to establish due to non - specific \n clinical symptoms and signs and the need for invasive diagnostic procedures for confirmation \n of ifi ( 4 , 5 ) . \n\nthe treatment is often challenging as it involves extensive surgical debridement of involved \n tissues in addition to antifungal drugs ( 4 ) .\nthe \n outcome is generally poor in resource constrained setups like ours but is gradually showing \n improvements ( 6 , 7 ) .\nthe data on outcome of ifis in children with t1d is scarce and is almost \n confined to invasive zygomycosis ( 4 ) . with an aim to \n determine the clinical spectrum and final outcome of children diagnosed with t1d and ifi \n over the last decade at our hospital , we performed a retrospective review of their medical \n records .\nthe analysis of hospital data of patients with t1d diagnosed to have a confirmed ifi was \n conducted at advanced pediatrics center of our institute which is a tertiary care referral \n center located in northwest india and included the period from march , 2004 to february , \n 2014 .\nall patients were diagnosed as t1d according to the international society for \n pediatric and adolescent diabetes ( ispad ) criteria published in 2000 and revised in 2009 \n ( 8 , 9 ) .\nthe \n diagnosis of associated fungal infection was based on microbiological and/or \n histopatholgical examination of tissue specimens .\ndata related to the basic demographic \n profile , age at the time of diagnosis , mode of initial presentation like diabetic \n ketoacidosis ( dka ) , imaging details , treatment modalities , duration of hospitalization and \n the final outcome were noted .\nten patients ( 6 girls and 4 boys ) amongst 524 children with t1d on follow up in pediatric \n diabetes clinic were treated for various ifis during the study period .\nthe mean ( sd ) age of \n presentation was 9.1 ( 3.4 ) yrs ( range 312 yrs ) .\nthe predisposing factors included poor adherence to insulin \n therapy resulting in poor metabolic control ( mean hba1c 9.3 1.2% ) and presence of acidosis \n in 9 patients and malnourished state in all ( mean bmi 12.6 1.2 kg / m ) .\nnine patients presented with dka . the commonest presenting \n feature related to fungal infection with suspected rhinocerebral involvement was facial \n and/or orbital swelling in 5 patients , followed by serosanguineous nasal discharge and \n ophthalamoplegia .\nthe most common site of fungal \n infection was nasal cavity and paranasal sinuses seen in 6 patients ; 5 of these were due to \n mucormycosis while 1 had aspergillus flavus .\nsinusitis involved ethmoid sinus in 5 patients \n and maxillary and frontal sinuses in 4 patients each ( table 1table 1clinical and \n laboratory profiles , treatment modalities and outcome of the study \n cohort ) .\nlung involvement was seen in 5 patients ; 2 of these \n had pleural and thymic involvement in addition .\nall patients \n showed neutrophilic leucocytosis with mean leukocyte count of 12.3 10/l . \n\nradiological investigations included contrast enhanced computed tomography ( cect ) scans of \n suspected involved sites in all patients .\n1.a : soft \n tissue opacities in frontal and ethmoid sinuses with blocked osteomeatal complex .\nb : \n opacification of right maxillary sinus . ) ; 2 of these had orbital extension . \n\n2.a & b : cect chest \n showing cavitatory pneumonia on right side . ) ; 1 patient , described elsewhere , showed \n empyema in addition ( 10 ) .\nanother patient had \n necrotic thick walled abscess in the thymus with consolidation of apical segment of right \n upper lobe and small subpleural nodular lesions in the right lower lobe ( 11 ) .\na : soft \n tissue opacities in frontal and ethmoid sinuses with blocked osteomeatal complex .\nconfirmation of diagnosis by direct microscopy of specimen ( smear / aspirate ) was made in 1 \n patient , by histopathological examination in 5 patients and by both techniques in 4 \n patients .\nculture on sabouraud dextrose agar grew rhizopus microsporum ( rhizopodiformis ) in \n 1 patient .\nthe most common yield was from smear or histopathological examination of tissues \n obtained at the time of surgical debridement of paranasal sinuses . in 2 patients who had \n serosanguineous nasal discharge\nthe \n identified etiological fungi belonged to the order mucorales in 9 cases ( 1 further \n identified as rhizopus microsporum ) and aspergillus flavus in 1 patient .\nthe mean time from \n presentation to diagnosis was 5.8 4.7 days ( range 114 days ) .\nall patients were treated with either intravenous amphotericin b ( conventional or \n liposomal ) or voriconazole for a targeted duration of 46 weeks .\nsurgical intervention was \n done in 8 patients and included debridement of paranasal sinuses by either endoscopy or \n external approach in 5 , excision of brain abscesses in 1 , resection of affected lung areas \n in 2 and excision of thymic abscess in 1 patient .\nmean duration of hospital stay was 41.7 \n 27.2 days ( range 290 days ) .\ntwo out of 10 patients died ; 1 with pulmonary mucormycosis \n suffered massive hemoptysis on day 14 of hospitalization while the other with disseminated \n aspergillosis died of a large bout of hematemesis and showed an intestinal perforation on \n autopsy .\nall survived children have remained well over a mean duration of 4.96 3.3 yrs \n ( range 9 mo9 yrs ) in follow up except 1 who continues to show mild restrictive pattern on \n pulmonary function tests .\ninvasive mycoses are uncommon but often lethal infections that disproportionately affect \n t1d patients with poor metabolic control ( 2 , 3 ) .\npoor adherence to insulin therapy , malnourished state \n and episodes of ketoacidosis particularly predispose children with t1d to develop ifis \n ( 2 , 3 , 11 , 12 ) .\nmajority \n of our patients had all these critical factors required for development of ifis .\npoor \n glycemic control may result in dysfunctions of macrophage phagocytosis , neutrophil \n chemotaxis and oxidative killing ( 1 ) , and ketoacidosis \n may induce a temporary block in binding of iron to transferrin providing free iron which \n enhances growth of many ifis particularly mucormycosis ( 2 , 13 , 14 ) .\npoor compliance to therapy as evidenced by poor clinic attendance , risk \n taking behaviors and recurrent admissions for dka has been documented to increase \n susceptibility to ifis ( 12 ) .\nsimilarly malnourished \n state resulting either from a poor glycemic control or poor dietary management predispose \n diabetic children to ifis ( 3 , 10,11,12 ) .\nthe presence of critical predisposing factors and an unusually high \n occurrence of ifis in our patients is probably a result of the prevailing healthcare \n situation related to the management of t1d in children in our setup ( 15 ) .\nlate diagnosis of diabetes due to lack of awareness of parents and \n the primary healthcare physicians is common in india ( 15 ) .\npoor metabolic control is also common due to \n lack of comprehensive diabetes care ( 15 , 17 ) .\nthere are only a few specialized centers and \n majority of the patients are treated by the primary care physicians who have limited \n knowledge about the disease and the modern treatment options ( 15 ) .\nadditionally , poor socioeconomic status often makes even the \n conventional insulin therapy and blood glucose monitoring unaffordable by the parents ( 15 ) .\nthe prevention of ifis in children with t1d requires \n early diagnosis of diabetes before onset of ketoacidosis , meticulous glycemic control in \n follow up and good nutritional management .\nimprovements in diagnosis and care of children \n with t1d in our country setup will probably lower the incidence of ifis in these patients in \n future .\nestablishment of an early diagnosis of ifi is important but is often difficult due to \n absence of specific symptoms ( 5 ) .\nwe believe that a \n high index of clinical suspicion in a setting of predisposing risk factors present in our \n patients resulted in rapid establishment of diagnosis .\npresence of subtle clinical features \n like dry cough , tachypnea persisting after resolution of acidosis , facial swelling , \n serosanguineous nasal discharge and low grade fever in poorly controlled , malnourished \n children who present in ketoacidosis are pointers to the presence of ifis ( 5 , 11 , 12 ) . in patients\nsuspected to have rhinocerebral \n involvement , smear examination of scrapings from nasal or sinus cavity are useful aid to \n rapid diagnosis .\nthe diagnosis of pulmonary ifi is highly probable if the ct scan shows \n cavitary pneumonia in a child with minimal pulmonary symptoms and previously described risk \n factors ( 10 ) .\nfine needle aspiration cytology can be \n very useful in reaching an early diagnosis of pulmonary ifis as compared to more invasive \n transbronchial biopsy ( 10 , 18 ) .\nthe cornerstone of management is a combination of antifungal drugs and early surgical \n debridement of involved tissues that may prevent extension of infection to the surrounding \n areas ( 4 , 19 ) . \n\ntreatment with antifungals alone is usually ineffective due to poor concentrations in \n affected tissues resulting from vascular invasion , thrombosis , occlusion and infarction \n ( 4 ) . in our patients who had rhinosinusitis ,\nearly \n surgical debridement probably prevented a contiguous extension of infection into the brain . \n\none \n of the 2 patients who received only antifungal therapy died ; the survivor received liposomal \n amphotericin b which had been previously reported to be able to achieve cure even in the \n absence of associated surgery ( 20 ) .\nthe success rates \n of a multimodal treatment approach in our study are similar to those achieved across many \n centers around the world ( 4 , 5 , 19 ) .\nthe long term morbidity \n related to consequences of the fungal disease was also minimal and confined to the sequelae \n of tissue loss from radical surgeries . in conclusion ,\nrapid and accurate diagnosis of ifis in children with t1d and a multimodal \n management approach involving early surgery , appropriate antifungal therapy and control of \n hyperglycemic state is successful in achieving a good outcome . to the best of our knowledge , \n\nours is the largest single center data and the first study from a developing country setup \n on ifis exclusively in children with t1d .", "answer": "abstractthere is scarcity of data on spectrum and outcome of invasive filamentous fungal \n infections ( ifis ) in children with type 1 diabetes ( t1d ) from developing countries . \n a \n retrospective review of medical records of children with t1d hospitalized with ifi over \n the past decade at the pediatric endocrinology and diabetes unit of a large tertiary care \n hospital of north india was performed with an aim to study their clinical spectrum , \n hospital course and final outcome . \n of the 10 patients studied , nasal / paranasal involvement \n was seen in 6 and pulmonary involvement in 5 patients . one patient developed disseminated \n disease . \n majority of the identified mycoses belonged to class zygomycetes order mucorales . \n \n early surgery along with antifungal therapy helped limit the extension of infection and \n achieve a good outcome in majority of patients . \n two patients died ; one with a late \n diagnosis of pulmonary mucormycosis and the other with disseminated disease . \n the longterm \n morbidity in the survivors was minimal . in conclusion , \n rapid diagnosis followed by a \n multimodal approach involving aggressive surgical debridement , appropriate antifungal \n therapy and control of hyperglycemic state is the key to good outcome in this otherwise \n lethal infection .", "id": 569} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfamilial adenomatous polyposis ( fap ) is an autosomal dominant syndrome caused by a germ line mutation of the adenomatous polyposis coli ( apc ) gene .\nsurgery for fap aims to minimize colorectal cancer risk while providing good functional and socially acceptable outcomes .\ncurative surgical treatment is total proctocolectomy with permanent ileostomy , but permanent stoma is an undesirable situation .\ntotal colectomy with ileorectal anastomosis ( ira ) and total proctocolectomy with ileal pouch - anal anastomosis ( ipaa ) are procedures of choice without need for permanent stoma .\nthe risk of rectal cancer due to the remaining rectal stump in ira continues to be the most important problem .\nthe risk of developing cancer in the rectal stump is 4 per cent at 5 years and 25 per cent at 20 years .\nthe result of a meta - analysis showed that functional outcome and quality of life were better after ira than ipaa . on the other hand same meta - analysis show that cancer occurring in 5.5 per cent after ira compared with zero after ipaa .\nas the risk of cancer and socially acceptable outcomes are the major considerations in deciding the best operative strategy for patients with fap .\ntechnically it can be more difficult by abdominal approach to transect the rectum just on the dentate line and to perform a ileal pouch - anal anastomosis .\nanorectal eversion may allow the assessment of the mucosa under direct visualization and resection remaining very little rectal mucosa and eases the hand - sewn or stapler - facilitated anastomosis .\nwe report here a patient with fap , who had total proctocolectomy resection via rectal eversion over the dentate line under direct visualization and ileoanal - j pouch anastomosis by double - stapler technique .\na 40-year - old female patient with a family history of colorectal cancer who has multiple adenomatous polyps from 4 cm proximal to the dentate line to the entire colon on colonoscopy was diagnosed as fap .\nthe operation was performed in the lithotomy position under general anesthesia . through the midline incision\nfirst of all colon and the rectum mobilized completely and routine colectomy was performed from 10 cm proximal to ileo - caecal valve to the rectosigmoid junction by a 50 mm linear stapler ( gia dst , covidien , mansfield , ma , usa ) . by gentle dissection\nileal j - pouch constructed from the distal ileum by a 100 mm linear stapler ( gia dst , covidien , mansfield , ma , usa ) .\nthe relaxing incisions were made on both sides of the meso - ileum to diminish the tension on the anastomosis .\nafter the relaxation incision the tip of reservoir easily reaches 3 cm beyond the lower margin of the symphysis pubis . by perineal approach rectal stump irrigation with an antiseptic solution\nwas done followed by insertion of a grasping forceps through the anus ( picture 1 ) and the rectal stump was everted through the anus by the mucosa turning inside - out ( picture 2 ) dentate line identified and the mucosa evaluated for the polyps . the remaining 15 cm long rectal stump resected just on the dentate line by ta linear cutter ( gia dst , covidien , mansfield , ma , usa ) .\n( pictures 3 and 4 ) then ileal j - pouch -anal anastomosis was performed by 29 mm circular stapler ( sdh29a , ethicon , ca , usa ) .\nfollows at 6th months the patient had no problem related to the anal incontinence and on digital examination anal sphincter functions found normal .\nsurgical options for fap patients that avoid the need for a permanent stoma include total colectomy with ira and restorative proctocolectomy with ipaa .\nipaa , which was first described by parks in 1978 for ulcerative colitis that permits total removal of all disease - prone mucosa but avoids the need for a permanent ileostomy while preserving anal continence and intestinal continuity .\na meta - analysis showed that functional outcome was better preserved after ira than ipaa for fap , with regard to stool frequency , need for defecation at night , incontinence and the need for pads .\nthese findings were expected in the patient with a retained , functioning rectum however , surprisingly , ipaa was not significantly different from ira with regard to stool frequency at night , day - time incontinence and need for antidiarrheal medication .\nwhether stapled or handsewn ipaa offers a better functional outcome has not been determined yet . for ipaa , it has been suggested that functional outcome is better for fap than ulcerative colitis .\nit has also been suggested that secondary ipaa , often performed following failed ira is associated with poorer functional outcome .\nthe most important consideration in deciding the best operative strategy for fap patients is the risk of cancer development .\naziz et al . showed that cancer occurring in 5.5 per cent after ira due to the remaining rectal stump compared with zero after ipaa in a meta - analysis .\nit is reported that there is no significant difference between ipaa and ira with respect to bowel obstruction , hemorrhage , intra - abdominal sepsis , anastomotic separation and wound infection in the same meta - analysis .\ncontroversy still exists about the technique to be used for the pouch - anal anastomosis .\nmucosectomy and handsewn anastomosis are necessary to remove the rectal mucosa as completely as possible . but\nthis technique takes longer time and has a relatively high risk of postoperative functional problems related to leakage and incontinence due to prolonged anal manipulation .\nstapling ipaa was first described by heald and allen in 1987 and is widely accepted to use for creation of the ileal pouches and ipaa .\nhowever to allow transanal insertion of the stapler head , it is usually unavoidable to leave a 12 cm segment of rectal mucosa over the dentate line that carries a risk of developing adenomas and cancer .\nadenomatous polyps , colonic metaplasia , and adenocarsinoma can occur in the terminal ileum of patients with fap , although the long term risk of pouch and dentate line cancer is not known .\nstudies comparing handsewn versus stapled ipaa have reported variable results . in a study of large number of patients of a single institution\nhad found that stapled ipaa had better outcomes and quality of life ( qol ) scores than those undergoing a handsewn ipaa .\ntechnical difficulties can still arise with the stapled ipaa technique , particularly with respect to accurate transection and closure of the anal canal at the anorectal junction by abdominal approach .\nrectal eversion permits the direct visualization of the mucosa and dentate line and has been suggested as a means of facilitating accurate anal transection and closure by use of either a handsewn purse - string suture or a linear stapler .\nhowever , there has been some concern regarding the potential of anorectal eversion to impair anal continence by causing traction injury to the anal sphincter complex or its nerve supply and thus worsen the functional outcome of restorative proctocolectomy .\nwilliamson et al . reported in a 50 patients series one year after restorative proctocolectomy with rectal eversion , all patients were continent , although two experienced leakage of mucus requiring a pad .\nforty - two patients ( 84 per cent ) could discriminate between faeces and flatus .\nthey noted that the eversion of the anorectum during restorative proctocolectomy impairs the motor and sensory functions of the anal sphincter but most patients achieved satisfactory anal continence , however , despite these physiological changes .\nhave reviewed the median 4 years follow - up clinical results of consecutive series of 41 patients operated with rectal eversion and reported that no patients had major incontinence and only 2 ( 6% ) had minor leakage .\nanorectal eversion may be achieved by the method described above , grasping forceps being introduced transanally to pull down the transected lower rectum , or by an alternative method described by scotte et al .\nwhereby the lower rectum is cross - stapled over a corrugated drain , introduced transanally , which can be used to facilitate eversion of the anorectum by traction from proximal end point of colon after rectal transection .\nwe conclude that , to facilitate accurate fashioning of stapled ipaa , anorectal eversion can be put into practice during restorative proctocolectomy .\nmuhittin aygar : data collection , data analysis , writing ; fahri yetiir : study design , data collections , data analysis , writing ; ebru arer : data collections , data analysis ; murat baki yldrm : data collections ; mesut zdedeolu : data analysis ; doukan durak : data collections ; abdssamet yaln , data analysis .", "answer": "introductionsurgery is the only treatment option for familial adenomatous polyposis ( fap ) . \n aim of surgery in fap is to minimize colorectal cancer risk without need for permanent stoma . \n there are especially two operation options ; total colectomy with ileorectal anastomosis ( ira ) and total proctocolectomy with ileo - pouch anal anastomosis ( ipaa ) . \n we report here a patient with fap who had resection via rectal eversion just over the dentate line under direct visualization and ileoanal - j pouch anastomosis by double - stapler technique.presentation of casea 40 yr . \n old female patient with fap underwent surgery . \n firstly , colon and the rectum mobilized completely , and then from the 10 cm . \n proximal to the ileo - caecal valve to the recto - sigmoid junction total colectomy was performed . \n rectum was everted by a grasping forceps which was introduced through the anus and then resection was performed by a linear stapler just over the dentate line . a stapled j - shaped ileal reservoir construction followed by intraluminal stapler - facilitated ileoanal anastomosis . \n follow up at six months anal sphincter function was found normal.discussionthere is only surgical management option for fap patients up to now . \n total colectomy with ira and restorative proctocolectomy with ipaa is surgical options for fap patients that avoid the need for a permanent stoma . \n anorectal eversion may be used in the surgical treatment of fap , chronic ulcerative colitis and early stage distal rectal cancer patients.conclusionj-pouch ileoanal anastomosis can safely be performed by rectal eversion and double stapler technique in fap patients .", "id": 570} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nglucose-6-phosphate isomerase ( gpi ) deficiency is the third most common red blood cell enzymopathy , after glucose-6-phosphate dehydrogenase ( g6pd ) and pyruvate kinase ( pk ) deficiency and is similarly associated with hereditary nonspherocytic hemolytic anemia ( hnsha ) .\nthe sole clinical manifestation in the majority of patients is chronic hsnha , ranging from mild to severe .\nmost cases of gpi deficiency are diagnosed during the neonatal and childhood period . to date , only two cases of prenatal diagnosis of gpi deficiency have been reported .\nadditionally , cases of postnatal diagnoses of hydrops caused by gpi deficiency were documented , usually without survival of the affected child 2,3 . in this case report\n, we describe a family in which two siblings have congenital hsnha due to gpi deficiency .\nthe first child was diagnosed at the age of 3 years , the second was monitored antenatally with repeated doppler ultrasound and was eventually treated for fetal anemia with repeated intrauterine transfusions . to our knowledge , this is the first case of prenatal diagnosis of gpi deficiency in cord blood , followed by successful intrauterine treatment of gpi - deficient fetal anemia .\na 33-year - old woman was referred to our center at 17 weeks of gestation because of an increased risk of fetal anemia .\ntheir first child , a 5-year - old girl , was born after an uneventful pregnancy and did not suffer from extreme neonatal jaundice or anemia .\nshe was diagnosed with gpi deficiency at the age of 3 years after her first documented acute hemolytic episode with signs of jaundice , severe anemia , and hemoglobinuria . following extensive investigation\ndna analysis showed the girl to be homozygous for the c.1615g > a , p.(asp539asn ) missense mutation in gpi .\nboth the mother and father were found to be heterozygous for the same mutation . at present , the girl remains clinically well , has normal growth and neuropsychological development but has evident chronic hemolysis treated with folic acid .\nshe has had infrequent exacerbations of hemolysis associated with minor childhood infections but nonsevere enough to warrant erythrocyte transfusions .\nthe current pregnancy was the fourth pregnancy of this couple , following two early miscarriages .\nthe parents refrained from early diagnostic chorionic villus biopsy or amniocentesis ( because of the risk of miscarriage ) , but instead opted for ultrasound monitoring for signs of fetal anemia ( measurement of the mca doppler peak systolic velocity ( mca - psv ) ) .\nthe pregnancy was followed up on a weekly basis , from 16 weeks of gestation onward . at 26 weeks of gestation ,\nfetal anemia was suspected , based on an increased mca - psv of > 1.5 multiples of the median ( mom ) ( fig.1 ) .\nthere is suspicion of fetal anemia when vmax in the middle cerebral artery exceeds 1.5 mom .\nthe first iut was given transplacentally in the umbilical cord root at 27 weeks of gestation .\npretransfusion cord blood was obtained for diagnostic testing , the fetal hemoglobin level was 7.4 g / dl .\nan uncomplicated intravenous transfusion of donor blood was performed , resulting in a posttransfusion hemoglobin concentration of 13.5 g / dl .\ngenetic analysis of fetal cells confirmed that the second child was also homozygous for the aforementioned mutations in the gpi gene .\nafter the diagnosis was made , folic acid was prescribed to the mother in a daily dosage of 5 mg .\nanother two iut 's were performed at gestational weeks 30 and 34 ( table1 ) .\nbased on the fact that the fetus needed repetitive intrauterine transfusions from 27 weeks of gestation onwards , labor was induced at 37 weeks to avoid further intrauterine transfusions .\na girl was born vaginally with apgar scores of 9 and 10 at 1 and 5 min , respectively .\nthe cord blood ph was 7.25 and her weight was 3620 g. neonatal jaundice was apparent immediately after birth .\nthe child required no exchange or top - up transfusions and was discharged at day 7 . at 4 weeks of age , despite resolving hemolytic parameters ( decreasing bilirubin and ldh ) the girl remained reticulocytopenic and required an additional blood transfusion for symptomatic anemia .\ntwo weeks after transfusion , spontaneous recovery of hemoglobin concentration was observed , with rising reticulocytes ( 105 10/l ) , normal bilirubin ( 11 mol / l ) , normal ldh ( 241 u / l ) , and low haptoglobin ( < 0.1 \nshe remains well and transfusion - independent at the current age of 5 months , while receiving folic acid replacement therapy .\nintrauterine transfusion data for the treatment of fetal anemia volume transfused : volume of transfused red blood cells .\ngpi is a dimeric enzyme which catalyzes the reversible conversion of glucose-6-phosphate and fructose-6-phosphate , the second step in glycolysis .\nthe gpi gene is located on the long arm of chromosome 19 and 31 mutations in the gpi gene are currently listed in the human gene mutation database ( www.hgmd.cf.ac.uk ) .\nthe majority of these mutations are missense mutations affecting key interactions of the enzyme 's active site 5 .\ngpi - deficient patients are either homozygous or compound heterozygous for such mutations , and are clinically characterized by chronic hemolytic anemia with hemolytic crises during infection or after ingestion of hemolytic drugs 6 .\nthe current therapy consists of blood transfusions and splenectomy for the most severe hemolytic cases 3,7 .\nit has been suggested that mutant gpi is inactivated faster with increasing rbc cell age than the wild - type enzyme 8 .\nthe manifestation in affected fetuses might therefore be milder because of the shorter lifespan of fetal rbcs .\nhowever , if fetal hydrops develops due to gpi deficiency , the prognosis is usually very poor 2,9 . in the literature ,\nperformed the first prenatal gpi deficiency diagnosis at 28 weeks of gestation by assessing the gpi characteristics in amniotic fluid cells .\ngpi deficiency was considered after the neonatal death of a previous child with hydrops . the second child in this family\nwas diagnosed antenatally as compound heterozygous for two different mutant gpi alleles and received an exchange transfusion after birth , which took place at 35 weeks of gestation 2 .\nprovided a first trimester gpi deficiency diagnosis on trophoblast cells obtained from chorionic villus sampling 1 . in the present case ,\ninstead , close fetal surveillance by ultrasound scanning was performed on a weekly basis , to monitor for signs of fetal anemia .\nthe diagnosis was confirmed by genetic analysis of dna of cord blood cells , sampled before the first iut .\niut is universally accepted as an efficient treatment for fetal anemia . in the leiden university medical center , serving as the dutch national referral center for fetal therapy since 1965 , it was the first time iuts were performed for fetal anemia due to gpi deficiency .\nwe prescribed folic acid supplementation to the mother to prevent the occurrence of megaloblastic anemia in the fetus .\npostdelivery the girl also received folic acid , as is standard in patients with hemolytic anemia .\nthis is a well - known phenomenon in children that received intrauterine transfusions and is thought to be induced by reduction in their own erythropoietin production .\nthe parents are both heterozygous for both mutations suggesting that although they were reported to be nonconsanguineous it is very likely that they stem from a common ancestor .\none possibility could be early exposure to oxidant agents which can trigger episodes of hemolysis . however , obstetric history of the second pregnancy showed no infection or known ingestion of oxidant drugs or food .\nwhitelaw et al . also reported a family of two affected siblings with different disease severity 2 .\npointed out that patients with the same mutation and deficient gpi activity can present with varying degrees of anemia and clinical impairment 7 .\nour findings confirm that the hemolytic episodes caused by gpi deficiency are unpredictable and emphasize the importance of prenatal monitoring of fetuses at risk . in conclusion , hemolytic anemia due to gpi deficiency can be severe and life threatening during fetal life .\nwe recommend frequent ultrasound monitoring for prenatal management of pregnancies in which there is an increased risk of fetal gpi deficiency , when parents decline early invasive testing . in this case , repeated intrauterine blood transfusions appeared to be effective for the treatment of severe fetal anemia due to gpi deficiency and may additionally have prevented the development of fetal hydrops and demise .", "answer": "key clinical messagehemolytic anemia due to gpi deficiency can be severe and life threatening during fetal life . \n when parents decline invasive testing , ultrasound monitoring of fetuses at risk is feasible . \n intrauterine transfusion can be effective for the treatment of severe fetal anemia due to gpi deficiency .", "id": 571} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe study population included 1177 patients who underwent different types of cardiac surgeries with cardiopulmonary bypass method at sina private hospital ( isfahan , iran ) , between april 2008 and september 2009 .\nall patients underwent a cardiovascular diagnostic procedure requiring the use of a contrast agent for left ventriculography , coronary or carotid angiography , and thoracic and/or abdominal aorta angiography before their surgeries .\nthus , the patients requiring emergency dialysis therapy or those that underwent the off - pump method surgery were excluded .\ndata for the studied patients including demographics , clinical characteristics , laboratory data , medical treatments , angiographic data , ( including amount and type of the contrast agent used ) , comorbid conditions and cardiac procedural data ( including its timing in relation to the preceding angiography ) , were collected by reviewing hospital record files in a computerized database .\nthe study was approved by the research ethics committee of isfahan university of medical sciences , isfahan sina heart center .\nthe contrast agent used were meglumine compound 76% ( urografin , bayer , usa ) as hyperosmolar , iopromide 370 ( ultravisit , berlex montville , usa , mfd . in : germany ) and iohexol 300 ( iopaque , iran or omnipaque 300 , usa ) as low - osmolar contrast agents .\nuse of nonsteroidal anti - inflammatory agents and other nephrotoxic drugs were avoided or withheld for 48 hours before angiography .\npostoperative renal risk was assessed using 2 different risk scores of a simplified predictive index for renal replacement therapy after cardiac surgery and a risk score for prediction of contrast - induced nephropathy.9 the main outcome of interest was the incidence of postoperative arf , defined as postoperative serum creatinine > 2 times baseline and/or the need for renal replacement therapy .\nthe mean value of baseline creatinine was 0.99 mg / dl.6 the obtained results are presented as mean sd , frequency , and percentage .\ncomparisons were made using chi - square test or fisher 's exact test for categorical variables and nonparametric test for continuous variables .\nthe amount of contrast media was entered into the model as both a linear ( continuous variable ) and a dichotomous term ( median or less and greater than median value ) .\nmultivariable logistic regression analysis was used to identify independent predictors of arf using variables found to have marginal association ( p > 0.10 ) on univariate analysis .\nodds ratio ( or ) and 95% confidence interval ( ci ) were constructed to provide an estimate of adjusted risk posed by post - procedural arf .\ncomparisons were made using chi - square test or fisher 's exact test for categorical variables and nonparametric test for continuous variables .\nthe amount of contrast media was entered into the model as both a linear ( continuous variable ) and a dichotomous term ( median or less and greater than median value ) .\nmultivariable logistic regression analysis was used to identify independent predictors of arf using variables found to have marginal association ( p > 0.10 ) on univariate analysis .\nodds ratio ( or ) and 95% confidence interval ( ci ) were constructed to provide an estimate of adjusted risk posed by post - procedural arf .\ncomparisons were made using chi - square test or fisher 's exact test for categorical variables and nonparametric test for continuous variables .\nthe amount of contrast media was entered into the model as both a linear ( continuous variable ) and a dichotomous term ( median or less and greater than median value ) .\nmultivariable logistic regression analysis was used to identify independent predictors of arf using variables found to have marginal association ( p > 0.10 ) on univariate analysis .\nodds ratio ( or ) and 95% confidence interval ( ci ) were constructed to provide an estimate of adjusted risk posed by post - procedural arf .\nof 1177 patients who underwent different types of cardiac surgeries after angiography , arf occurred in 465 subjects , 2 of these patients needed dialysis .\nmean dose of hyperosmolar and low - osmolar contrast agents used overall were 1.23 and 1.21 ml / kg , respectively .\nbaseline clinical features between the two cohorts with and without postoperative arf are listed in table 1 .\npostoperative arf was more prevalent in older and male patients ( p = 0.003 and 0.002 , respectively ) , and those with a higher history of hypertension(p = 0.012 ) , but prevalence of other risk factors as well as left ventricular ejection fraction were similar in both group of patients .\nthere was a significant difference between last pre and post- operative creatinine in both groups ( p < 0.001 ) .\npatients with arf were also more likely to have undergone combined coronary artery bypass grafting and valve surgery the same day as angiography and also underwent more postoperative intra - aortic balloon pump insertion ( iabp ) ( table 2 ) .\nthe patients with arf were more likely to have received higher doses of both hyper - osmolar and low - osmolar contrast agents compared to mean doses ( p = 0.17 and 0.035 , respectively ) .\nhowever , the time interval between cardiac surgery and last catheterization was not different between the patients with and without arf ( p > 0.05 ) ( table 2 ) . clinical and demographic characteristics of the studied population contrast agent and cardiac surgery data overall postoperative peak creatinine was highest on day 0 ( figure 2 ) , then decreased and remained significantly unchanged after this period ( p < 0.05 ) .\nhowever , overall prevalence of acute renal failure during follow - up period ( figure 2 ) had a changeable trend and had the highest rates in days 1 ( 53.57% ) and 6 ( 52.17% ) ( p < 0.05 ) .\nrelationship between the time interval flanked by angiography and surgery and postoperative serum creatinine relationship between the time interval flanked by angiography and surgery and postoperative acute renal failure independent correlates of postoperative arf in a multivariate model are listed in table 3 .\ncombined coronary artery bypass grafting ( cabg ) and valve surgery was the strongest predictor of postoperative arf ( or : 4.976 , p = 0.002 ) , followed by intra - aortic balloon pump insertion ( or : 6.890 , p = 0.009 ) and higher dose of contrast agent ( or : 1.446 , p = 0.031 ) .\nthe major findings of the present study were that the higher dose of the used contrast agents besides some other determinants such as combined coronary bypass and valvular surgery as well as iabp insertion could effectively predict post - procedure acute arf .\non the other hand , the use of high dose of contrast agent was strongly related to the incidence of arf after combined cardiac surgery .\nin fact , our data confirmed findings of other investigations that arf after cardiac surgery was associated with the amount of prescribed contrast agents . in a similar study by ranucci and his colleagues,6 cardiac surgery performed on the day of cardiac catheterization and higher dose of contrast agent\nalthough these investigators demonstrated a correlation between the time interval of cardiac catheterization and surgical procedure with the incidence of acute arf , we could not demonstrate this relationship in our multivariable regression model . in another study by del duca\net al4 cardiac catheterization performed within 5 days before operation , baseline glomerular filtration rate of less than 60 ml / min and prolonged cardiopulmonary bypass duration , were significant risk factors for acute renal failure after cardiac surgery . moreover , other studies established similar clinical and surgical characteristics associated with increased risk of arf after cardiac surgery , including age,168 baseline serum creatinine,10 diabetes mellitus,1113 congestive heart failure,1012 emergency surgery,1114 concomitant valve surgery with coronary artery bypass grafting,11 preoperative use of iabp,14 and low cardiac output syndrome in the postoperative course.1415 however , these studies consistently failed to account for the influence of the timing between previous angiography and cardiac surgery and the amount of the contrast agent used in this event .\nmultiple mechanisms have been suggested to contribute to the renal damage following cardiac diagnostic procedures , including non - pulsatile flow , embolization , and trauma to the blood constituents , hypothermia , and activation of known inflammatory pathways.16 iodinated contrast as a common contrast agent , after causing a brief period of vasodilation , can cause sustained intrarenal vasoconstriction and ischemic injury .\nthe ischemic injury sets off a cascade of events largely driven by oxidative injury , causing death of renal tubular cells .\nif a sufficient mass of nephron units are affected , then a recognizable rise in serum creatinine will occur.1718 therefore , minimizing the amount of contrast agent during preceding angiography is recommended .\nsimilar studies need to be conducted regarding alternate imaging modalities that do not use iodine - based contrast agents to obtain information about ventricular function , valvular dysfunction and aortic pathologic characteristics.6 finally , strategies to prevent contrast - induced nephropathy during angiography that is continued in the postoperative period may also have the potential to decrease arf after early cardiac surgery .\nmms designed the study and drafted this manuscript ; mg carried out the study and drafted the tables ; pn carried out the study and drafted the tables ; hsh helped in designing the study ; hms helped in final drafting ; ak helped in designing and carried out the study ; pms data analysis ; and nf data collection .", "answer": "background : there is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure ( arf ) . \n therefore , in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of arf after cardiac surgery was investigated.methods:data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined . \n the influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative arf were assessed using multivariable logistic regression.results:the patients who progressed to arf were more likely to have received a higher dose of contrast agent compared to the mean dose . however , the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without arf ( p = 0.05 ) . overall , postoperative peak creatinine was highest on day 0 , then decreased and remained significantly unchanged after this period . \n overall prevalence of acute renal failure during follow - up period had a changeable trend and had the highest rates in days 1 ( 53.57% ) and 6 ( 52.17% ) after surgery . \n combined coronary bypass and valve surgery were the strongest predictor of postoperative arf ( or : 4.976 , ci = 1.613 - 15.355 and p = 0.002 ) , followed by intra - aortic balloon pump insertion ( or : 6.890 , ci = 1.482 - 32.032 and p = 0.009 ) and usage of higher doses of contrast media agent ( or : 1.446 , ci = 1.033 - 2.025 and p = 0.031).conclusions : minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative arf in patients undergoing cardiac surgery , but delaying cardiac surgery after exposure to these agents might not have this protective effect .", "id": 572} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nunfortunately this demand is more than the supply in terms of surgeons performing these surgeries .\nrobotic surgery fills the gap between having skills and not having one . a surgeon with limited skills\nthis leads to added advantage both to the patient as well as the surgeon . notwithstanding the cost , robot helps to duplicate the laparoscopic surgeries which otherwise would be beyond the reach of surgeon with limitation of skills . in april 2005 ,\ndavinci robot was food and drug administration cleared for gynaecologic procedures based on preliminary evidence of safety and efficacy from their early experience with myomectomy and hysterectomy at the university of michigan .\nrobotics is best for single quadrant surgery and for fixed structures and hence is especially useful in gynaecological surgery .\nit has added advantages of 3d perception , wristed instrumentation , intuitive movements and dexterity .\nsince november 2009 until date , we have performed 80 robotic gynaecological cases in galaxy care laparoscopy institute , pune .\nwe standardized the port positions as \n a 12 mm camera port was placed 2 cm above the umbilicus.an 8 mm robotic port on the either side was placed 10 cm lateral and 12 cm caudal to the camera port.the right sided robotic port was a mirror image of the left robotic port.two assistant 10 mm ports were placed pararectally at the level of the camera port . \n \nan 8 mm robotic port on the either side was placed 10 cm lateral and 12 cm caudal to the camera port .\ntwo assistant 10 mm ports were placed pararectally at the level of the camera port .\nthe robotic cart was docked from in between the legs a zero degree scope was used for the procedure . for all the surgeries ,\nrobotic docking time.console time surgical time.blood loss.complications.conversion to either lap or open \n robotic docking time .\nconversion to either lap or open for the oncological surgeries , other parameters such as paracervical clearance , nodal yield and vaginal margins were also recorded .\nof the total of 80 gynecological cases performed robotically in our institute , 29 were benign and 51 were malignant cases .\nof the benign cases , 24 were hysterectomies for various complex benign pathologies like big fibroids , previous abdominal surgeries .\n2 tubotuboplasties , 1 endometriotic cyst excision , 1 metroplasty , 1 rectovaginal fistula repair were also performed with good results at our institute . of the total of 51 oncological cases performed robotically ,\n27 were robotic radical hysterectomies for cancer cervix , 10 total robotic hysterectomies with bilateral salpingo - opherectomy with ilioobturator node dissection for cancer endometrium , 2 were total robotic hysterectomy with bilateral salpingo- opherectomy and omentectomy for cancer ovary , 7 were exenterations , 5 were parametrectomy .\ntotal robotic hysterectomy : we compared our outcomes with those of previously done standard studies as shown in the table 1 .\ncomparison of our data of total robotic hysterectomy with previously reported series our operative time , estimated blood loss was considerably lower when compared with other standard international studies .\nthere was no conversion to open surgery ; furthermore no major intraoperative or postoperative complications were noted .\nrobotic radical hysterectomy : we have compared the results of our radical hysterectomies with those of other standard reported cases in literature . as shown in table 2 our operative time , effective blood loss was less than that of others . two cases of ureteric fistulas reported were during initial phase after acquiring the robot . as we got acquainted with these procedures\ncomparison of our data of radical robotic hysterectomy with previously reported series table 3 below provides comparison of parameters between our laparoscopic cases with the robotic cases .\ntotal robotic hysterectomy : we compared our outcomes with those of previously done standard studies as shown in the table 1 .\ncomparison of our data of total robotic hysterectomy with previously reported series our operative time , estimated blood loss was considerably lower when compared with other standard international studies .\nthere was no conversion to open surgery ; furthermore no major intraoperative or postoperative complications were noted .\nrobotic radical hysterectomy : we have compared the results of our radical hysterectomies with those of other standard reported cases in literature . as shown in table 2 our operative time , effective blood loss was less than that of others .\ntwo cases of ureteric fistulas reported were during initial phase after acquiring the robot . as we got acquainted with these procedures\ncomparison of our data of radical robotic hysterectomy with previously reported series table 3 below provides comparison of parameters between our laparoscopic cases with the robotic cases .\nthe advantages of robotic assistance include enhanced dexterity , improved 3-d vision , and more intuitive instrument manipulation .\nit thus helps to bridge the skill gap for a laparoscopic surgeon helping to overcome skill limitations .\nthis may make a complex surgical task more accessible to surgeons without much laparoscopic experience .\nplacement of robotic trocars has to be in such a way to prevent collision of robotic working arms and accessory ports .\nthe accessory ports are used for retraction , for energy sources like ligasure or for applying clips .\nthe preoperative planning helps in performing a smooth procedure as well as reducing the docking time .\nthe docking time was previously 30 min which later reduced to 10 min because of standardization of ports , team gaining experience and getting acquainted with the system . in 1989 , laparoscopy was first used to perform a hysterectomy . in 2002 , the use of the davinci robot for hysterectomies was first reported .\npayne and dauterive concluded that robotic hysterectomy was quicker and with less risk for abdominal conversion than standard laparoscopy .\nwe have an extensive experience in laparoscopic hysterectomies with which we have started doing robotic hysterectomies .\nthe patients with high body mass index and patients with narrow pelvis were preferred for robotic procedure . the time taken and blood loss was the same as in laparoscopy .\nstandardization of procedure and proper training of the technique was necessary to prevent complications and for safe outcome .\nthe salient steps of our technique \n use of combined anaesthesia , ergonomic port positioning , use of myoma screw for traction , use of bipolar forceps medial to uterine stump , colpotomy at the level of uterosacral ligaments . \n \nuse of combined anaesthesia , ergonomic port positioning , use of myoma screw for traction , use of bipolar forceps medial to uterine stump , colpotomy at the level of uterosacral ligaments .\nall our patients had stage iv endometriosis and the rectum and ureter could be separated well due to the high magnification and the intuitive movements of the robot .\nrobotic - assisted laparoscopic surgery promises to provide advantages in the management of women with severe endometriosis secondary to 3-dimensional visualization , decreasing surgeon 's fatigue and hand tremors and improving surgical precision . with the davinci system\n, the challenges of visibility with laparoscopy can be overcome as well as many other limitations of laparoscopy .\nhence , the field of gynaecologic oncology has begun adopting the davinci system in performing oncological surgeries due to its shorter learning curve and ease of use .\nstudies , suggest that robotic radical hysterectomy ( rrh ) is preferable over laparoscopic radical hysterectomy ( lrh ) due to its decrease in blood loss , hospital stay , recovery time , and complications\n. however , rrh appears to be equivalent to lrh in the hands of experienced surgeons . in patients predicted to have a high chance for conversion to open from laparoscopy , davinci system may prevent conversion .\nthe international federation of gynaecology and obstertrics staging requires lymphadenectomy for assignment of stage , and morbid obesity is usually cited as the most common limiting factor for completing a satisfactory lymphadenectomy .\nthe multi - centre gynecologic oncology group lap-2 trial with 1,696 laparoscopic cases reported a 23% conversion rate and a mean operative time of 3.3 hrs , indicating difficulty with a significant proportion of cases .\nreasons for not adopting laparoscopic surgery often cited by surgeons are prolonged operating times , surgeon fatigue , a difficult and prolonged learning curve , and lack of formal training in advanced laparoscopic technique .\nwe have reported our experience of laparoscopic gynaec oncology procedures such as radical hysterectomy , anterior exenteration and total pelvic exenteration .\nthe use of hybrid technique and using bipolar energy near the ureters have prevented any further fistulas in subsequent patients .\nthe two larger series from boggess et al . , and lowe et al . ,\nshow that there were no transfusions , length of stay was one day , and total complications were less than that usually associated with either open or laparoscopic approaches .\nthe results are comparable to those of laparoscopy , robot helps to duplicate many procedures with exceptional laparoscopic skills .", "answer": "aims : to study the role of robotics in various gynaecological cases , benign and malignant.materials and methods : a total number of 80 cases have been analyzed . \n operative time , estimated blood loss , hospital stay , complications , conversion rates have been retrospectively studied in all cases . \n nodal yield , vaginal margin and paracervical clearance have been studied in all malignant cases . \n this investigation was conducted at a single minimal access surgery institute.results:of total 80 cases , 29 were benign and 51 were malignant cases . in benign cases , total robotic hysterectomies were 24 , 2 cases of tubotuboplasty , 1 case of endometriotic cyst excision , 1 case of metroplasty and 1 case of rectovaginal fistula . in 51 cases , \n 37 of radical hysterectomy , 9 exenterations and 6 were parametrectomy . \n in benign cases , mean operative time was 80 min , estimated blood loss was 20 ml , mean hospital stay was for 1 day , no major complications and no conversions . in malignant cases , \n mean operative time was 122 min , estimated blood loss was 50 - 100ml , 2 cases of ureteric fistulas and no conversions , nodal yield was 30 , vaginal margin was 2.5 - 3.8 cm and para cervical clearance was 3 - 3.5 cm.conclusions:ours is the largest series of robotic surgery in gynecological procedures in india . \n benign and malignant cases were addressed robotically showing the feasibility .", "id": 573} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalopecia areata ( aa ) is a chronic inflammatory disease of the hair follicles and nails , its etiology is unknown , probably multifactorial with evident autoimmune and genetic components . the first clinical description of aa is attributed to celsus ( 14 - 37 b.c . ) and the designation aa was given by sauvages .\nthe importance of genetic factors in aa is underlined by the high frequency of a positive family history in affected individuals . in most reports , these range from 10% to 20% of cases .\na study in monozygotic and dizygotic pairs found a concordance rate of 55% for alopecia amongst monozygotic twins with no concordance among the dizygotic pairs . though it can affect any age group , demographical data on aa is still lacking .\ntwo brothers aged 5 and 7 years presented to the outpatient department with complaints of asymptomatic patchy loss of scalp hair for the past 2 and 4 months respectively .\nthere was no similar complaint in any other family member , siblings and no history suggestive of systemic involvement , drug intake , trauma , pus filled lesions or any other skin eruptions .\nmucocutaneous examination revealed multiple smooth patches of alopecia ranging from 2 cm 2 cm to 4 cm 6 cm over occipital and vertex area of elder child and multiple patches over occipital and temporal region measuring 2 cm 2 cm to 2 cm 4 cm of the younger one [ figure 1a and b ] .\n( a ) multiple areas of nonscarring alopecia involving the occipital and vertex area in a 7-year - old child ( b ) multiple areas of nonscarring alopecia involving the occipital and temporal area in sibling 5-year - old surface of the patches was smooth with no apparent changes .\nhistopathological examination of the biopsy sample from the alopecia patch from the scalp confirmed the diagnosis , which showed inflammatory infiltrate in and around the bulbar region of hair follicle .\nalopecia areata is t cell mediated autoimmune disease with genetic predisposition resulting in partial and total nonscarring alopecia .\nscalp is the predominant site of involvement with the most common clinical pattern involving multiple areas of patchy hair loss .\nmost patients develop aa before the age 40 years with 11 - 20% of all cases occurring in children .\nthe ratio of male : female in aa in pediatric age group is 1:1 where as in adolescent and adult it is more common in female .\nhuman leukocyte antigen ( hla)-dq3 and hla - dqb1fnx0103 alleles appear to be marker for genetic susceptibility to aa with the latter serving as a special genetic marker for more severe variants .\nthe diagnostic pathologic feature is peribulbar lymphocytic inflammation ( swarm of bees ) predominately cd4 + cells along with cd8 + t cells affecting anagen follicles or follicles in early catagen .\nshort , easily extractable broken hairs , known as exclamation mark hairs , are often seen at the margins of the bald patches during active phases of the disease .\nthe scalp is the first affected site in most cases , but any hair - bearing skin can be affected .\nthe term alopecia totalis is applied to total or almost total loss of scalp hair , and alopecia universalis is the loss of all body hair .\nchildren with aa demonstrate an increased levels of activated t cells leading to various autoimmune diseases like vitiligo , thyroiditis , connective tissue disorders , lichen planus , type 1 diabetes , and pemphigus foliaceous .\ngeometric and superficial pits are typical of aa whereas deep and irregularly distributed pits are seen in psoriasis and atopic dermatitis . familial aggregation of aa has been studied and it has been found that estimated lifetime risk has been 7.1% in siblings , 7.8% in parents , 5.7% in offspring .\naa has been also reported after allogenic bone marrow transplantation from an affected , hla matched sibling .\nmenon and kiran reported a case of concomitant occurrence of aa in the sibling with emphasis on environmental precipitating factors .\nevidence based management of aa in children is limited due to the lack of well controlled randomized studies .\nreassurance should be given to patients with limited disease as spontaneous remission occurs in 80% of patients .\nvarious treatment options tried in aa are topical , intralesional , and systemic corticosteroids , topical immunomodulators , and topical irritants like dithranol , psoralen plus ultraviolet a therapy , excimer laser therapy .", "answer": "alopecia areata ( aa ) is a t cell mediated autoimmune disease with multifactorial etiology resulting in partial and total nonscarring alopecia . \n we hereby report a case of two brothers ( aged 7 and 5 years ) presenting with coincidental aa over scalp which is a rare presentation .", "id": 574} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n\t\t\t\t the prevalence of childhood obesity has been increasing at unsettling rates across the globe .\nin addition to striking the developed world , this pattern has also been noted in developing countries undergoing rapid epidemiological transitions , including those in east africa . in sudan , a study of children in secondary school in the capital khartoum found that rates of overweight and obesity were 28.5% and 5.6% , respectively .\nrates of obesity for younger schoolchildren in east africa remain unclear , though obesity at younger ages may carry greater importance because younger children possess improved potential for early intervention .\nhypertension , a notable sequela of obesity , was already common in sub - saharan africa but has been reported to be worsening in prevalence in recent years .\nhypertension often goes underdiagnosed in children , in part because its accurate diagnosis requires the use of standardized growth charts specific for age , gender , and height , with hypertension defined as a systolic and/or diastolic blood pressure > 95th percentile and pre - hypertension defined as systolic and/or diastolic blood pressure 9095th percentile .\nunderdiagnosis of hypertension may be even more common in developing countries , where medical care is limited to symptomatic diseases , and childhood hypertension has been overlooked in lieu of more urgent disease . given the importance of childhood hypertension and pre - hypertension in determining adult cardiovascular disease outcomes , our goal was to determine the prevalence of hypertension and pre - hypertension among urban school children in sudan and to determine whether hypertension was associated with obesity in this population .\nthese data serve to alert providers in developing and developed countries to the extent of the current obesity epidemic .\nsudan is in east africa , bordering egypt on the north , ethiopia on the east , kenya , uganda , and congo on the south , and central african republic , chad , and libya on the west .\nsudan has 2.5 million square kilometers and 37 million inhabitants , of whom 57 million live in the capital of khartoum .\ntraditionally an impoverished country , sudan has experienced an economy that has expanded rapidly with oil exportation over the past 10 years , with khartoum being the epicenter of economic activity .\nthis was a cross - sectional study using a sample of 304 children aging six through twelve years from two schools randomly selected in khartoum , the capital of sudan .\nall students were given a questionnaire to be filled out by their parents , which asked for signed consent for their child to participate in the study , in addition to other demographic and health information .\nethics approval was obtained from the university of medical sciences and technology ( khartoum , sudan ) research ethics board .\nquestionnaires sent to parents inquired regarding the child 's age , gender , and health conditions , both previous and current .\nthe questionnaire also asked whether there was a medical diagnosis of hypertension , diabetes , or heart disease among blood - related family members and which family members were affected .\nthe child was classified as having a positive family history only if disease was present in a first - degree relative .\nbody weight was measured to the nearest tenth of a kilogram on a calibrated digital scale , with the child 's shoes removed .\nheight was measured with the child standing with shoes removed , measured in centimeters to the nearest millimeter .\nblood pressure was measured twice , once manually and once digitally , using an appropriate cuff size , based on arm circumference , and the mean was taken and used for analysis . body mass index ( bmi ) , defined as body weight in kilograms divided by the square of height in meters ( kg / m ) , was used as the measure of obesity in this study .\nbmi is an accepted measure of obesity in clinical practice , and its use in children has been supported internationally by the international obesity task force ( iotf ) , which agreed that it provides a reasonable index of adiposity and in that it is a simple and inexpensive measure .\nit provides reliable estimations , with the exceptions of extremes of age , height , and musculature . \nbmi was categorized according to the centers for disease control and prevention ( cdc ) age- and sex - specific growth charts .\nthe following categories were used : underweight < 5th percentile ; normal weight , 5th to 85th percentile ; overweight , 85th to 95th percentile ; obese , > 95th percentile . \nblood pressure was categorized according to bp tables from the fourth report on the diagnosis , evaluation , and treatment of high blood pressure in children and adolescents , using age and height percentiles , with normotension defined as a bp under the 90th percentile , prehypertension 90th to 95th percentile , and hypertension greater than 95th percentile or an absolute systolic bp ( sbp ) of 120 mm hg or diastolic bp ( dbp ) of 80 mm hg .\nchildren were also classified as hypertensive if they were taking antihypertensive medication or had been diagnosed with hypertension previously .\ndescriptive statistics were calculated for gender , family history , and bmi and bp categories .\nanalyses were performed using the chi - squared test for association , and multinomial logistic regression to investigate the odds of systolic and diastolic prehypertension and hypertension with overweight or obesity , controlling for family history of hypertension .\nanalyses were conducted using stata 10.0 ( 2008 statacorp lp , college station , tx ) .\ncomplete data on height , weight , bp , and family history were available for the entire sample ( n = 304 ) .\nthe average age of participants was 7.8 years , with a median age of 9 years ( range 612 years ) .\nall were of sudanese nationality , and the gender distribution was 236 female ( 77.6% ) and 68 male ( 22.4% ) . \nthe number of children who were overweight was 45 ( 14.8% ) , and 32 were obese ( 10.5% ) .\nfemales had a nonsignificant trend toward higher rates than males of overweight ( 14.0% versus 11.8% ) and obesity ( 11.0% versus 5.9% , p > .05 ) .\nprehypertension was detected in 15 ( 4.9% ) participants and additional 15 ( 4.9% ) had hypertension , all on the basis of bp measurement , as none were taking antihypertensives or had a previous diagnosis of hypertension .\nthe rate of elevated bp ( prehypertension and hypertension combined ) in males and females was 13.2% versus 8.9% .\na family history of hypertension was reported for 64 ( 21.1% ) of the participants overall , including 20.1% of children with a normal blood pressure , 20.0% of those with pre - hypertension , and 40.0% of hypertensive children ( table 2 ) . though there is a higher rate of family history with hypertension compared to normal bp or prehypertension , this difference was not significant by chi - square test ( p > .05 ) . regarding the association between bmi and bp , 31.2% of obese children had hypertension , versus 17.8% of overweight children and 5.3% of normal bmi children .\nthese results were found to be highly statistically significant by pearson chi - squared test ( p < .001 ) .\nfurther classification of prehypertension and hypertension into systolic and diastolic is stratified by bp category in table 3 for descriptive purposes . \nthe results are given as the relative risk of being in a certain bp category by weight category compared to children with a normal bmi , adjusting for gender and family history .\nafter adjustment for these factors , sudanese children who were obese had a relative risk of systolic hypertension of 14.7 compared to their normal - weight counterparts ( p < .01 ) .\nwe found a high rate of overweight and obesity among 612-year - old primary schoolchildren in urban sudan , with 14.8% of the children overweight and 10.5% obese . despite moderate rates of hypertension reported previously among children in sub - saharan africa up to 11% in rural children , suggesting an underlying genetic predisposition we found that obesity and not family history was the factor most strongly associated with hypertension in our sample .\nobese children carried a relative risk of 14.7 for systolic hypertension after adjustment for family history , while family history of hypertension was not significantly associated .\nthat obesity was so highly correlated with hypertension in a part of the world more commonly linked to undernutrition underscores the pervasiveness of the obesity epidemic and its sequelae throughout the world .\nrates of hypertension in sub - saharan africa have been noted to be increasing among adults [ 5 , 6 , 13 ] concurrent with rising rates of obesity in urban areas .\nprior studies to demonstrate these effects among children in east africa have been lacking , however .\nthe appearance of early cardiovascular sequelae of obesity at these young ages suggests that urban areas in the developing world may begin to face increasing health concerns in children related to the obesity epidemic . as in other sub - saharan african nations ,\nthese high rates of obesity in sudan are felt to be due to the epidemiological transition that has come with westernization .\nwhile food availability has improved , dietary habits have shifted away from traditional agricultural choices to an increase in processed foods as seen in western countries .\nthe appearance of obesity - associated hypertension in children may signal that developing countries are likely to face similar difficulties as developed countries in overcoming lifestyle choices .\nsimilar reports of obesity have been reported from other less - developed nations outside of africa .\na study of schoolchildren in beijing , china , reported that approximately 20% of children were overweight or obese . in karachi ,\npakistan , an almost identical prevalence of 25% of children had a high bmi , with 6% of children overweight and 19% obese . in iran ,\nrates of hypertension in other populations are less clear , although increasing bmi has been consistently associated with increased blood pressure throughout childhood [ 1719 ] .\nthe total number of children involved was relatively small ( 304 subjects ) , particularly with respect to boys ( 68 subjects ) .\nin contrast to many studies of blood pressure in african children that did not determine rates of hypertension based on normal ranges for height , age , and gender , we determined blood pressure status for each of our participants , dividing children into normotensive , pre - hypertensive , and hypertensive categories . in common with other studies [ 20 , 21 ]\n, we used the average of blood pressure measurements at a single time point for each subject , acknowledging that measuring blood pressure on separate occasions is necessary for the diagnosis of hypertension on a clinical basis .\nit is possible that the prevalence of hypertension in our sample would be lower were three measurements used to determine hypertension .\nother measurements estimating adiposity ( waist circumference , bioelectrical impedance , and mri ) are more specific to the amount of fat mass .\nnevertheless , for population - based studies bmi correlates well with these other measures and remains widely used as a definition of obesity in hypertension research [ 2325 ] .\nin conclusion , primary schoolchildren in urban sudan exhibited a high degree of overweight and obesity , and hypertension among these children was more closely linked to obesity than to family history . that obesity - associated cardiovascular sequelae exist in the developing world at such young ages\nis a harbinger of worsened cardiovascular outcomes in sub - saharan africa in the future . to overcome these trends , children in urban settings in africa are likely to require similar dietary and activity lifestyle adjustments as needed by their counterparts in developed nations", "answer": "cardiovascular disease ( cvd ) frequently has roots in childhood , including following childhood - onset hypertension . \n incidence of cvd has increased in developing countries in east africa during recent urbanization . \n effects of these shifts on childhood hypertension are unclear . \n our objectives were to ( 1 ) determine the prevalence of hypertension among primary schoolchildren in khartoum , sudan ; ( 2 ) determine whether hypertension in this setting is associated with obesity . \n we performed a cross sectional study of 6 - 12y children from two schools randomly selected in khartoum , sudan . \n height , weight , bmi , bp and family history of hypertension were assessed . \n age- , height- and gender - specific bp curves were used to determine pre - hypertension ( 9095% ) and hypertension ( > 95% ) . of 304 children , 45 ( 14.8% ) \n were overweight ; 32 ( 10.5% ) were obese ; 15 ( 4.9% ) were pre - hypertensive and 15 ( 4.9% ) were hypertensive . \n obesity but not family history of hypertension was associated with current hypertension . in multiple logistic regression , adjusting for family history , children who were obese had a relative - risk of 14.7 ( ci 2.45 - 88.2 ) for systolic hypertension compared to normal - weight children . we conclude that overweight and obesity are highly prevalent among primary schoolchildren in urban sudan and are strongly associated with hypertension . that obesity - associated cardiovascular sequelae exist in the developing world at young ages \n may be a harbinger of future cvd in sub - saharan africa .", "id": 575} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\n2D magnetic MOFs with micron-lateral size by liquid exfoliation\n\nPaper sections:\n\nscalable as it only provides very small quantities of the 2D material, thus preventing its use in important applications such as membranes, 18 sensors 19 or catalysis. 20 On the contrary, the quality of the layers obtained by liquid exfoliation is much lower since the sheets are typically damaged by the solvents used for their separation and stabilization. 21 In addition, the size of the exfoliated layers is typically much smaller and it is very difficult to go down to the monolayer. However, this approach provides an attractive, simple and scalable method for the creation of ultrathin nanosheets from layered materials, which can be applied to MOFs. 22 In view of these features, a challenging goal is to obtain 2D nanomaterials with micrometer-scale lateral dimensions and nanoscale longitudinal dimensions via liquid exfoliation, which would benefit from an easy processability while retaining the structural integrity.
Herein we demonstrate the production of nanosheets of good quality of 2D magnetic MOFs with lateral sizes of several microns using a liquid exfoliation approach. The compounds of interest are the so called MUV-1-X (MUV = Material of the University of Valencia), a family of layered coordination polymers of formula [Fe(bimX) 2 ] (HbimX = benzimidazole functionalized in the 5-position with X = H, Cl, Br, or CH 3 ). Very recently we have shown that they can be exfoliated down to the monolayer using a dry micromechanical procedure. 11 These crystalline materials are formed by tetrahedral Fe(II) centers linked via benzimidazolate bridges in order to form neutral layers of square Fe(II) networks separated by weak van der Waals interactions. From a magnetic point of view they behave in bulk as canted antiferromagnets ordering at ca. 19-20 K.
MUV-1-X single crystals (X = H, Cl, Br, or CH 3 ) were prepared following the solvent-free methodology previously used by our group. 11,23 Crystals of MUV-1-Cl were used as model compound of this family in order to assess the best conditions for the liquid exfoliation, analysing the effect of different parameters such as source of energy, solvent, time, temperature, concentration, and centrifugation. The exfoliation process is illustrated in Figure 1.
2.5 mg of MUV-1-Cl was initially added in 20 ml of a given solvent, which was subsequently introduced both in a sonic bath and in the sonication tip to examine the impact caused by the source of sonication in the structure of the material. As has been previously established, 22 the tip-assisted sonication can reach higher power than the bath-assisted sonication, resulting in the fragmentation onto smaller crystals with undefined morphologies. This is clearly evidenced in our case, where the sonication tip causes the disintegration of the material, whereas the sonication bath successfully induces the delamination (see Figures S2 and S3). In fact, the damage to the flakes is much reduced when the sonication bath is applied at low temperature using an ice bath.
The different solvents that were used in order to study their relevance in the delamination process were selected due to their different properties: hydrogen bond donors, hydrogen bond acceptors and non-polar solvents. Specifically, we tested water, acetonitrile, diethyl ether, methanol, propanol, acetone, tetrahydrofurane, hexane, dichloromethane, and dimethylformamide. Delamination was successful with most of these solvents, with nanosheets of large lateral sizes observed with optical microscopy and Transmission Electronic Microscopy (TEM) (see Table S1 and Figure S4-S18). However, the behaviour of the exfoliated flakes differs with the solvent, with decomposition or agglomeration found in some cases in several hours (see Table S1), as shown by Raman spectroscopy and TEM (see Figures S4-S18). Only acetone and acetonitrile are found to be suitable solvents for a correct delamination, with higher stability and quality flakes observed for the former. In fact, exfoliated flakes are stable for several days in a colloidal suspension in acetone at low temperatures (see Figures S19 and S23).
After establishing the best solvent and source of energy to proceed with the delamination, we optimized the exposure time and concentration used in the exfoliation process. First, the delamination was analysed by changing the exposure time of the coordination polymer to sonication, resulting in a greater number of flakes with a large lateral size and small thickness in one hour. A reduced time of sonication causes a low delamination, resulting in very thick nanosheets, whereas a longer time of sonication causes the fragmentation of the nanosheets, resulting in very small lateral size (see Figures S24-S33). Second, we studied the effect of concentration on the exfoliation process, varying it from 0.0625 mg/mL to 0.75 mg/mL. An optimized concentration was 0.125 mg/mL, with ca. 20% of the material successfully exfoliated; at lower concentration, practically no exfoliation was detected (see Figure S34). Finally, a study was carried out using different centrifugation conditions. This aspect was very important as it allowed us to achieve dispersions with homogeneous thicknesses (Figures S35-S42). The point at which the flakes were obtained with a more effective compromise between quantity and thickness is centrifuging at 8000 rpm, for 1 hour and maintaining a temperature of 5 \u00b0C. The low temperature used in the centrifugation was shown to be critical, as also the storage temperature, which prevented the agglomeration and decomposition of the exfoliated material. Using the above optimized conditions, we proceeded to an in-depth characterization of the exfoliated nanosheets of MUV-1-Cl. The
\n\nMUV-1-X Exfoliated nanosheets\nMUV-1-X Isolated nanosheet <<< MUV-1-X Bulk isolation of the nanosheets were conducted by spin coating on Si/SiO 2 substrate a few drops of the top of the colloidal solution containing the exfoliated material, resulting in large amount of material (see Figures S43-S45). In this way flakes of different thicknesses and lateral sizes were isolated. Figure 2 shows flakes with lateral sizes much larger than previously reported, achieving values larger than 8 \u00b5m (additional AFM images can be found in Figures S46-S48 in the Supporting Information), with thicknesses as low as 4 nm, corresponding to 3-4 layers. Although this is still far from the results obtained with purely inorganic materials, which are of the order of several microns of lateral size, 24 exfoliated MUV-1-Cl flakes are much larger than other exfoliated 2D MOFs, with typical flakes of the order of 0.1-2 \u00b5m lateral sizes. 21 Figure 3 shows the characterization of the exfoliated MUV-1-Cl flakes using Raman spectroscopy, AFM and Selected-Area Electron Diffraction (SAED). This multi-technique analysis allows the unequivocal demonstration of the chemical composition of the material, which has not been damaged after delamination. Quite remarkably, SAED reveals that the crystallinity of the material is maintained after liquid delamination.
In addition, different members of the isoreticular MUV-1-X family, with X = CH 3 , Br, and H, were successfully exfoliated following the same protocol as the established to delaminate MUV-1-Cl, achieving in all cases very similar results (Figure 3 and Figure S49-S64). This indicates that the proposed methodology is valid for the different materials with different surface properties.
As far as the magnetism of these 2D MOFs is concerned, we noted that the magnetic signal of these flakes is too weak to be detected through conventional SQUID measurements. Still, a spectroscopic technique such as electron paramagnetic resonance (EPR) has shown to be very useful in this context. Thus, EPR of a suspension in acetone of few MUV-1-Cl flakes, which are intrinsically EPR silent, shows a sextet signal that can be assigned to a Mn 2+ impurity, which is present in the acetone solvent (Figure 4 and Figure S66). This sextet corresponds to a hyperfine coupling constant of 96 G (A = 270 MHz), compatible with the weak crystal field coming from oxygen-based Mn 2+ complexes, such as [Mn(H 2 O) 6 ] 2+ . 25 Interestingly, this Mn 2+ sextet is shifted towards lower fields below a temperature of 16-18 K, which is close to the ordering temperature of the bulk material (19-20 K). This strongly suggests that the ultrathin flakes retain the magnetic ordering of the bulk, showing small differences in the T c value that may be due to dimensionality effects, 9 or simply to the distortion in the layers caused by the exfoliation process. The origin of this shift may be a consequence of the Zeeman splitting caused by the internal magnetic field created by the layers in the weak ferromagnetic state, which has to be added to the applied magnetic field. This requires close contact between the Mn 2+ impurity and the sheets. We speculate that in the acetone suspension, Mn 2+ is probably adsorbed on the surface of the sheets, or even coordinated to terminal benzimidazole ligands located at sheet defects. Similar magnetic shifts were previously observed in hybrid molecular magnets obtained upon insertion of paramagnetic metallocenium cations into layered oxalate magnets.
\n\n26\nIn summary, this work shows the possibility of exfoliating the layered coordination polymers MUV-1-X using a liquid exfoliation method to obtain suspensions of magnetic 2D MOFs of high-quality, formed by layers with lateral sizes of several microns and very low thickness (down to 4 nm). Interestingly, these magnetic nanosheets maintain their structural integrity and the magnetic ordering. This study paves the way for the use of these metal-organic nanosheets in functional heterostructures via a chemical approach which is unachievable by dry exfoliation.
", "answer": "The isolation in large amounts of high-quality flakes of 2D MOFs remains a challenge. In this work, we develop a liquid exfoliation procedure to obtain nanosheets for a whole family of Fe-based magnetic MOFs, MUV-1-X. High-quality crystalline layers with lateral sizes of 8 \u00b5m and thicknesses of 4 nm, which keep the structural integrity and magnetic properties, are obtained.Since the discovery of graphene, other layered materials formed by one or few atomically-thin layers (aka. 2D materials) have been isolated. 1,2 In this context, 2D MOFs are emerging as an important class of 2D materials of current interest, 3 in different areas such as catalysis, 4 membranes, 5 energy, 6 electronics, 7 or magnetism. 8 In magnetism for example, these 2D MOFs have shown to provide unique examples of magnetic layers which, in contrast to the 2D inorganic analogues, 9 are chemically stable and more versatile from the point of view of their functionalization. 10-12Both top-down -involving the exfoliation of crystalline layered materials 13 -and, to a less extent, bottom-up methodologiesinvolving a direct synthesis of the 2D material from molecular precursors 14 -have been used to obtain 2D MOFs. Within the group of top-down methodologies, two different techniques have been developed to obtain nanosheets from the bulk, namely micromechanical 15 and liquid exfoliation approaches. 16 The quality of layers that can be obtained using these two approaches is very different. The micromechanical exfoliation, also known as the Scotch-tape method, allows to separate the layers without any interaction with solvents, thus affording very high-quality layers, which are necessary to explore the physics in the 2D limit. 17 However, this dry approach is extremely difficult to apply to MOFs due to the fragility of the coordination compounds. 10 In addition, it is not", "id": 576} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nas in other countries worldwide , the number of traffic accidents in turkey is increasing each year , from 500,664 in 2000 to 1,034,435 in 2010 .\nthe high number of traffic accidents yielding injuries and fatalities makes them of great importance to emergency departments ( ed ) .\nit is thought that by determining common injuries resulting from accidents and by taking the necessary precautions , morbidity and mortality could be reduced .\nthe material damage resulting from accidents has a strong adverse effect on a country s economy .\nphysicians who are aware of the costs of traffic accidents will be able to take a more cost - effective approach to trauma . by retrospectively evaluating the files of patients who presented at hacettepe university medical faculty adult ed because of traffic accidents between 2000 and 2010 , this study aimed to determine the epidemiology of traffic accidents and to analyze the costs .\nit was determined that between 1 january 2000 and 31 december 2009 , 3712 patients presented at hacettepe university adult ed following traffic accidents .\nfor all the patients included in the study , a record was made of various demographic and epidemiological characteristics such as age , gender , arrival time , arrival condition , time to arrival at hospital , presence of any life - threatening condition , glasgow coma score , revised trauma score ( rts ) , findings and results , outcomes ( admittance to hospital , self - discharge , death ) , and length of stay ( los ) in the ed .\ninjuries were evaluated separately as head , thorax , abdomen , extremities and other injuries .\nthe details of costs pertaining to that date with the patient file number were recorded .\nmean costs per capita were calculated separately for each year , and then the mean cost for each year was converted to american dollars according to the mean exchange rate for that year .\ndifferences between groups were evaluated by kruskall - wallis , mann - whitney , and wilcoxon tests according to variable type and parametric test assumptions .\nthe study comprised an examination of 2003 patient files that could be accessed from a total of 3712 patients who presented at hacettepe university medical faculty ed following traffic accidents between 1 january 2000 and 31 december 2009 .\nthe patients included in the study were 901 females ( 45% ) and 1102 males ( 55% ) with a mean age of 39.6816.15 years ( range 1593 years ) . when the years were examined , the most presentations following traffic accidents were in 2004 with 307 ( 15.4% ) , followed by 2005 with 287 ( 14.3% ) .\nthe highest incidence was seen in the months of may , july , and june , with 217 ( 10.8% ) in may and the lowest number of presentations was in february and march at 120 ( 6% ) for each month . when the distribution of cases was calculated according to season , it was determined that the most of 28.4% of presentations occurred in the summer months . in respect of the time of presentation\n, it was determined that the most presentations ( n=671 , 33.5% ) were between 6 pm and 12 am ( midnight ) ( table 1 ) . in the evaluation of the time taken to reach the emergency department ,\nit was determined that 51.5% presented within the first 30 minutes after the accident , 76.5% within the first 60 minutes , and 88.7% within the first 2 hours ( table 2 ) .\nmost patients ( 1675=83.6% ) arrived at the ed by ambulance . according to the manner of injury in the patient records , 1907 ( 95.2% ) were from motor vehicle accidents ( table 3 ) .\nthe most frequently seen trauma was head trauma ( 18.3% ) , followed by extremities ( 16.7% ) , thorax ( 7.3% ) , and abdominal trauma ( 3.5% ) .\ndistribution of the outcomes according to the age , glascow coma scale(gcs ) and revised trauma scores(rts ) were given in table 6 .\nthe results as to whether or not there were life - threatening conditions according to the forensic reports written in the ed are given in table 8 .\nmortality occurred in 7 patients ( 0.4% ) who had been given a non - life - threatening report .\nthe costs of 1998 patients in this study were evaluated and the costs of 5 patients were not evaluated .\nthe mean cost was found to be 983.54364.4 tl ; minimum 3 tl , maximum 84,941 tl .\nthe costs for each year were converted to american dollars using the mean exchange rate for that year .\nthe study examined 2003 records that could be accessed from a total of 3712 patients who presented at hacettepe university faculty of medicine emergency department following traffic accidents between 1 january 2000 and 31 december 2009 .\nthe patients were 901 females ( 45% ) and 1102 males ( 55% ) , which is similar to the sex distribution found in the literature .\nthe age of patients in the study ranged from 15 to 93 years , with a mean age of 39.6816.15 years .\nreported a mean age of 35.814.3 years , marmor et al . reported 27 years , and etinolu et al . reported 35 years [ 36 ]\nthis mean age of traffic accidents affects the young and productive population ; therefore , in addition to financial loss , there is thought to be a loss to the workforce and daily functioning .\nwhen the number of traffic accidents was examined according to year , the lowest number was 83 ( 4.1% ) in 2000 .\nthis result may be due to a lack of records in the past and it is thought that positive steps have been taken over the years in improving recording systems .\nhighest numbers of presentations occurred in may , july , and june . in a study by varol et al . , the most accidents occurred in august ( 17.9% ) .\nthe observation that most traffic accidents occur in the summer months agrees with data in the literature .\nthis may be due to evening rush - hour traffic congestion , limited visual fields at night , and human error due to tiredness , lack of attention , and alcohol intake .\nthe hours of most presentations were found to be 6 pm to 12 am ( midnight ) in a study by aygencel et al .\n, 12 pm ( noon ) to 6 pm by beyazta et al . , and 3 pm to 7 pm by mishra et al . .\nin the current study , 1607 patients ( 83.62% ) were brought to the ed by ambulance .\nas 52.5% in a similar study . in a previous epidemiological study of trauma in turkey , patient transfer by ambulance\nthe increase in this rate is thought to be due to use of the 112 ambulance system having become effective and public awareness of first aid and emergency procedures .\nthe ed was reached within the first 30 minutes after the accident by 51.5% of the patients in the current study . in a study by wong et al . , the mean period before reaching hospital was 28 minutes .\nthe period before reaching hospital is known to be significant for mortality and morbidity . of the patients in the current study ,\nthe mortality rate associated with the motor vehicle accidents was 46 ( 2.4% ) and 1 ( 1.6% ) with motorcycle accidents .\neken et al . showed a mortality rate in motorcycle accidents of 5.7% . in a study by mon et al . , the injury and mortality rate of motorcycle accidents was 3.5 times higher than that of other motor vehicle accidents .\nthe result of the current study is at the expected level as there is widespread motorcycle use in ankara .\nthe most frequently determined pathology was head trauma ( 18.3% ) , followed by extremity trauma ( 16.7% ) , and these results agree with the literature . taking these results into consideration , precautions giving protection in the event of an accident should be considered a priority in motor vehicle safety equipment . in a study by weninger et al . , head trauma occurred in 66% of patients , thoracic trauma in 55% , abdominal trauma in 55% , spinal trauma in 27% , at least 1 long bone fracture in 70% , and multiple fractures in 51% .\na reason that these rates are higher than those of the current study could be that only high velocity motor vehicle accidents were included in that study . in the current study ,\n1639 patients ( 81.8% ) were discharged from the ed , 248 ( 12.4% ) were hospitalized , and 48 ( 2.4% ) died .\nreported that 89.7% of patients were discharged from the ed , 8.4% were hospitalized , and 1.1% died .\nit is necessary to have monitoring in different departments of patients who have been stabilized by initial interventions , both in terms of patient morbidity and ed turnover . in the current study ,\nthe average los in the ed was 4031416 minutes , with a median of 180 minutes . in a study by mishra et al .\n, 10% of cases spent less than 1 hour at the hospital , 41.6% spent 16 hours , and 48.3% spent more than 6 hours . in the current study , only los in the ed was calculated and the total los in the hospital was not included .\nthis excessive period and the low rate of hospitalization may be associated with a bed shortage in our hospital . in the current study ,\nthis is an expected outcome due to factors such as comorbidities and weaker compensation mechanisms in the elderly .\ntraffic accidents constitute the great majority of criminal cases that present at the ed . of criminal cases presenting at the emergency department ,\nin the current study , 7 patients ( 0.4% ) died who had been given an emergency department report that there was no life - threatening condition . in the light of this result , it is thought that it is necessary to be very thorough in the preparation of forensic reports , and physician training on the writing of such reports should be reinforced .\nannual losses to the turkish economy of 350450 million dollars are caused by traffic accidents . in the current study ,\nthe mean cost per capita was found to be 9834364 tl ( 7553357 dollars ) .\nif labor force and functional losses are considered , this amount could be much higher .\n1910 pounds sterling by morris et al . , and 3600 euros by jacobs et al . .\nwhen compared with these studies , the mean cost of the current study was lower , which may be due to differences in economic status and costs of healthcare in various countries .\nremoving unnecessary tests would reduce costs , but the basic solution is to increase preventive measures against traffic accidents and driver education must be improved .", "answer": "backgroundtraffic accidents are ranked first as the cause of personal injury throughout the world . \n the high number of traffic accidents yielding injuries and fatalities makes them of great importance to emergency departments.material/methodspatients admitted to hacettepe university faculty of medicine adult emergency department due to traffic accidents were investigated epidemiologically . \n differences between groups were evaluated by kruskall - wallis , mann - whitney , and wilcoxon tests . \n a value of p<0.05 was accepted as statistically significant.resultswe included 2003 patients over 16 years of age . \n the mean age was 39.616.1 and 55% were males . \n admissions by ambulance and due to motor vehicle accidents were the most common . in 2004 \n the rate of traffic accidents ( 15.3% ) was higher than the other years , the most common month was may ( 10.8% ) , and the most common time period was 6 pm to 12 am ( midnight ) . \n about half of the patients ( 51.5% ) were admitted in the first 30 minutes . \n life - threatening condition was present in 9.6% of the patients . \n head trauma was the most common type of trauma , with the rate of 18.3% . \n mortality rate was 81.8% . \n the average length of hospital stay was 403 minutes ( 6.7 hours ) and the average cost per patient was 9834364 tl.conclusionsfurther studies are needed to compare the cost found in this study with the mean cost for turkey . \n however , the most important step to reduce the direct and indirect costs due to traffic accidents is the prevention of these accidents .", "id": 577} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthere is a subgroup of patients with temporomandibular disorder who nomadically pass from one dentist to another seeking bite correction .\ntheir occlusal discomfort is characterized by an uncomfortable sensation mainly affecting corrected dentition , crowns , or dentures in which no abnormality is clinically detectable .\nthis phenomenon is known as the phantom bite syndrome ( marbach 1976 , 1978 ; marbach et al 1983 ; jagger and korszun 2004 ) . despite repeated failures of dental surgery , these individuals persist in seeking bite correction from a succession of dentists .\nthe condition is refractory to most treatments including psychotherapy ( marbach 1976 , 1996 ) .\nwe have reported previously that tricyclic antidepressants can be effective in treating phantom bite syndrome ( toyofuku 2000 ) .\nhowever , the patients non - acceptance of the anticholinergic side - effects of these drugs usually prevents high enough doses being achieved .\nmilnacipran is an antidepressant which , similarly to the tricyclics , inhibits the reuptake of serotonin and norepinephrine but without the side - effects of the older antidepressants .\nrecently it has been reported that milnacipran has been used to treat various oral psychosomatic disorders such as glossodynia and temporomandibular disorder ( toyofuku 2003 ; toyofuku et al 2003 ; toyofuku and miyako 2004 ) .\nwe present here a preliminary study of the efficacy and safety of milnacipran in a series of patients complaining of occlusal discomfort and diagnosed as suffering from phantom bite syndrome .\nwe report here the results with 7 patients who came to the department of dentistry and oral surgery at the fukuoka university hospital in japan in 20032004 complaining of occlusal discomfort and diagnosed as suffering from phantom bite syndrome .\nsix patients were outpatients and one was hospitalized for severe fatigue and because of difficulty of attending the hospital since she lives on a remote island .\nall patients met the following criteria ; preoccupation with their dental occlusion and a false belief that their dental occlusion was abnormal , a long history of repeated dental surgery treatment failures with persistent requests for the occlusal treatment that they are convinced they need , no history of significant psychiatric illness , absence of obvious psychosocial problems .\nthey all had a relatively high intelligence and socioeconomic status which enabled then to undergo endless costly and time - consuming dental treatments .\nmilnacipran was initially administered at 30 mg / day on a twice daily schedule and adjusted weekly according to clinical symptoms and tolerance . the effect on occlusal discomfort\nwas measured using a 100 mm visual analogue scale ( vas ) where baseline severity was arbitrarily set to 100 .\nseverity of depression was assessed using the zung self - rating scale for depression ( sds ) .\n( marked improvement with only occasional mild symptoms ) , mild ( some improvement but with considerable residual symptoms ) , or poor ( little or no improvement ) .\none patient was lost to follow - up after 2 weeks because he refused to continue , stating that he was feeling well .\nfive of the remaining 6 patients were improved at the end of the 4-week treatment period , 3 markedly , and 2 mildly improved .\npatient 6 was unco - operative and refused to complete the vas and sds self - rating evaluations at the end of the study .\nshe insisted , however , that she had had no improvement at all over the 4 weeks of the study . during the study she refused any increase of the dose of milnacipran , insisting on dental surgery bite correction instead of medication .\nscores of 0 improvement were therefore used for this patient for the sds and vas analyses ( table 2 ) .\noverall , the occlusal discomfort felt by the patients was considerably decreased between baseline and week 4 ( table 2 ) .\nthe level of depressive symptoms was also decreased as indicated by a 47.8% decrease in sds .\nthere was , however , no correlation between individual reductions in sds and vas values .\nthree patients reported adverse effects ( headache , dizziness , and nausea , table 2 ) .\nall effects , however , were slight and transient , disappearing within a few days .\npatients exhibiting the phantom bite syndrome are considered to be refractory to most dental treatment .\nthey become increasingly difficult to manage after repeated failures of dental surgery resulting in frustration for both the dentist and the patient who is usually convinced of the incompetence of their dentist and moves on to another dentist .\nthe present study suggests that milnacipran may be a beneficial treatment for such oral psychosomatic disorder patients with occlusal discomfort known as phantom bite syndrome .\nthis is a small number , it is the largest study on phantom bite to have been reported to date .\nthe department of dentistry and oral surgery at fukuoka university has an excellent reputation in the treatment of dental psychosomatic disorders and for this reason patients are referred to this department by psychosomatic doctors from all over southern japan .\nin addition 40% of patients in the present study came spontaneously to the department because of its reputation among patients .\nin addition to the small number of patients , the obvious weakness of the study resides in its open - label design .\nhowever , the refractory nature of the disorder ( the average duration at the beginning of the study was over 3 years ) gives some credence to the observed results .\nthis technique probably lacked precision , however , since some of the patients said they had difficulty in expressing quantitatively their symptom on a visual analogue scale .\nthe development of other patient - rated measures such as a modified faces scale as used to quantify pain in children ( bieri et al 1990 ) would clearly be helpful for studying this and similar oral psychosomatic conditions .\nnone of the patients had any history of significant psychiatric illness , indeed they were all strongly resistant to the idea of psychiatric referral or treatment .\nsix of the 7 patients were , however , mildly depressed as rated by the zung sds scale and one more moderately depressed . in 5 out of 6 patients completing the study , the depression scores improved considerably to a level considered to be asymptomatic . in general , however , there was no correlation in this study between the decrease in sds score and decrease in occlusal discomfort as indicated by the vas .\nthis result and clinical observations suggests that the efficacy of milnacipran in reducing occlusal discomfort is more likely to be a direct effect on the somatosensory system rather than on any associated depression .\nmilnacipran and other serotonin - norepinephrine reuptake inhibitors have been shown to be effective on a variety of pain disorders both associated with , and independent of , depression ( briley 2003 , 2004 ) .\nmilnacipran is not , however , an analgesic as such and these effects have been suggested to involve an action on serotonin and norepinephrine neurotransmission ( stahl and briley 2004 ) .\nthe action of milnacipran appears to be to correct the erroneous integration of peripheral signals by the central nervous system .\na further example of milnacipran correcting erroneous integration of peripheral signals is in fibromyalgia where normally non - painful stimuli are perceived as pain signals ( allodynia ) ( vitton et al 2004 ) .\nit would seem likely that the effect of milnacipran on phantom bite seen in the present study is another manifestation of this activity on the two monoamines systems where the occlusal discomfort experienced by the patient is the result of an erroneous integration of peripheral signals . in conclusion , after 4 weeks treatment , 5 of the 6 patients completing the study responded to milnacipran with clinically significant improvements in their occlusal discomfort .\nthis suggests that milnacipran may be an effective and well tolerated treatment for phantom bite in oral psychosomatic disorder patients .\nphantom bite is , however , a chronic syndrome and the promising effects seen here after 4 weeks need to be followed up over a much longer time period .", "answer": "phantom bite syndrome is characterized by an uncomfortable sensation mainly affecting corrected dentition in which no abnormality is clinically detectable . despite repeated failures of dental surgery , sufferers persist in seeking bite correction from a succession of dentists . \n the etiology pathogenesis of phantom bite is unknown but some consider the syndrome to be a psychosomatic disorder . \n seven patients with this syndrome were treated with the serotonin and norepinephrine reuptake inhibitor milnacipran for 4 weeks . \n one patient withdrew after 2 weeks because he was feeling \n well . \n at the end of the study , 5 of the 6 patients completing the study reported significant improvements , with a mean decrease in occlusal discomfort of 55.3% , as indicated by a visual analogue scale . \n this result appeared to be independent of any antidepressant effect . \n only minor and transient side - effects were observed . it is suggested that milnacipran may be a helpful treatment for phantom bite but this needs to be confirmed by further and longer term studies .", "id": 578} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin their companion article , tononi and cirelli argue that i have missed the big picture by conflating questions of sleep function with the underlying mechanisms . as i have discussed elsewhere\n[ 2 , 3 ] , understanding sleep function is of central importance to biology .\nany theory of sleep function must also grapple with universal traits of sleep , some of which were enumerated in their response .\nthere are other theories of sleep function and many of the theoretical arguments made in support of shy ( e.g. , a need for offline states , sleep homeostasis , and brain metabolism ) apply to them .\nmy position is that this evaluation must always include a discussion of mechanisms , because they can not be disentangled from functional questions . \nthe underlying message from tononi and cirelli is that what really matters is the \nthe end result [ 1 , page 4 ] rather than how you get there .\ni find this an odd position to take and a backward step in our pursuit of sleep function .\nthe goal of science is to understand how nature works . that includes an empirical pursuit of physical mechanisms .\nscientists should therefore be skeptical of any theory of sleep function that fails to elucidate the underlying mechanisms that govern the proposed function . in this regard ,\nthe proponents of shy are in an indefensible position when they argue that the mechanisms have no bearing on whether the core claim of shy is true or false [ 1 , page 3 ] .\nthey have bearing because if the underlying mechanisms are not sleep dependent then the theory is wrong .\nincidentally , the theory is also wrong if the proposed mechanisms do not exist . while it may be true that these mechanisms are complex and perhaps different in different species , that is not a reason to ignore them . on the contrary , that is a reason to explore them .\n. indeed , i do find shy confusing because the proposed mechanisms ( to date ) seem inconsistent with what is actually known about synaptic plasticity .\nmoreover , their imprecise terminology fogs the issue . they claim that they never meant that the potentiation in wakefulness is hebbian ( i.e. , some form of ltp ) , yet it is difficult to draw any other conclusion based on their own words . their liberal and interchangeable use of the words long - term potentiation , ltp , or \nthis is because ltp is not short - hand for stronger synapse ; it has a precise meaning and commonly refers to hebbian processes . in their rebuttal\n, they back peddle from their past specific language regarding the significance of neuromodulator release and the expression of plasticity molecules in shy .\nthere is , however , little ambiguity in their original description of how these events purportedly promote ltp ( or ltp - like events ) during wake versus sleep [ 4 , 5 ] . \nthe concepts and terminology of synaptic homeostasis and scaling predate shy and there is simply no mistaking the broad similarities between synaptic scaling and what is described in shy .\nfor example , here is a more complete excerpt from tononi and cirelli . like activity - dependent synaptic scaling ( emphasis added ) , however , sleep - dependent downscaling would affect most or all of a neuron 's synapses . in this respect , downscaling is conceptually different from long - term depression , which affects select groups of synapses , or depotentiation , which affects only recently potentiated ones \ntherefore , their use of these terms , if in fact they mean something else , is perplexing . the distinctions they make between their version of downscaling and scaling proper are welcome , but quite subtle when compared to the overall similarities .\nfor example , synaptic homeostasis is not only manifested at the level of firing rates as implied by tononi and cirelli .\nthat is one outcome of a homeostatic adjustment of synaptic weights in a network , as measured , for example , by mepscs [ 7 , 8 ] .\nthis point seems moot , since tononi and cirelli cite changes in firing rates and mepscs as evidence of shy [ 9 , 10 ] . in the end , it really does not matter what new name they give to their process ( or set of processes ) that weakens synapses .\nthe point i was making , and which they missed , is that any form of plasticity ( especially if possibly novel ) should be examined through the prism of known facts about hebbian and non - hebbian plasticity .\ncase in point : i never stated that the downscaling of shy is identical to synaptic scaling as currently understood in the field .\ni instead argued that since the concepts of scaling figure prominently in shy , and because scaling is an accepted means of globally adjusting synaptic weight , it is logical to examine the claims of shy based on what is known about synaptic scaling .\n synaptic renormalization from synaptic scaling , but this name change does not inoculate shy against scrutiny .\n the veracity and validity of a scientific theory is not solely determined by the amount of data piled on one side of a scale .\nit is also determined by a careful examination of each piece of evidence , pro and con . upon close examination\n, threads of supportive findings may unravel , and when contrary evidence is properly considered , an otherwise impressive mass of findings may collapse . a large part of their response is a long catalog of supportive data some of which i included in my review .\nhowever , as i pointed out , careful examination reveals alternative explanations for some of their results .\nthey also largely ignore evidence consistent with net increases in synaptic strength after sleep , or findings that question their hypothesized relationship between synaptic potentiation and slow - wave electroencephalographic activity ( swa ) [ 11 , 12 ] .\nthese findings are consistent with my original discussion and completely in opposition to predictions of shy .\nwhen these are also considered the universality of shy , and its utility as an explanation for why we sleep , becomes questionable .\n in my original review , i considered biological processes other than sleep that might explain some findings ascribed to shy .\nthese included the cumulative effects of natural patterns in brain temperature ( and in mammals , glucocorticoid release ) across the 24-hour day or after sleep deprivation .\ntononi and cirelli present a number of arguments against these ideas , but i have a better idea\nfor example , why not examine the effects of cooling or warming on drosophila synaptic proteins ( which are altered by changes in temperature as small as 8c ; not as they state 20c ) ?\ntononi and cirelli argue strenuously that shy is a theory of function , yet they support their argument with cellular and molecular findings that have no demonstrable function . rather than elaborate upon already dense theoretical arguments about the functional importance of shy , why not demonstrate it empirically ? in science , no argument , no matter how beautifully crafted , trumps a good experiment .\n in his discussion of sleep theories 50 years ago , nathaniel kleitman reminded his readers of the cautionary tale of ptolemy of alexandria .\nptolemy was a revered scholar in the 2nd century ad who codified hundreds of years of prior greek astronomy and mathematics into what came to be known as the ptolemaic universe .\nthe ptolemaic universe held that the stars , planets and sun revolved around the earth , embedded in overlapping crystalline spheres .\nthis theory of the natural world was elegant , mathematical , and even highly predictive of astronomical events .\nthe lesson from ptolemy is that scientific theories are ultimately judged not only by their power to explain , but by the validity of their physical mechanisms . \ntononi and cirelli argue that for shy to be valid , it does not matter how synapses are weaker after a sleep period , just that they are .\nbut ptolemy reminds us that this is not enough ; scientific truth comes from asking hard questions about how things actually work .\ni do not question their results , showing for example , changes in evoked responses or mrnas consistent with shy .\nfirst , they have not identified how sleep actually alters synaptic strength in any species .\nsecond , they have not experimentally excluded the role of other biological processes that coincide with sleep .\na final consideration is that if shy is a scientific hypothesis , then tononi and cirelli should propose an experimental outcome that would force a rejection of shy .", "answer": "in a recent article i reviewed an influential theory of sleep function , the synaptic homeostasis hypothesis ( shy . ) according to shy , sleep renormalizes synapses that are potentiated during prior wakefulness . \n i concluded that while shy is a seminal theory with important implications about sleep function and the brain , its underlying mechanisms are poorly defined . in an accompanying article , the authors of shy responded at length . \n their reply is thoughtful and provocative , but unfortunately many of the points i raised were not accurately represented or addressed . in this brief commentary , i attempt to clarify some points of confusion . \n i also explain why any theory of sleep function is incomplete without an understanding of the underlying cellular mechanisms .", "id": 579} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnontuberculous mycobacteria ( ntm ) have emerged as an increasingly important pathogen in the last two decades . unlike other environmental pathogens that are largely opportunistic in patients with malignancy and immunodeficiency , as well as transplant recipients , ntm can cause significant disease in otherwise healthy individuals .\nthe ntm most commonly associated with pulmonary infection is the mycobacterium avium complex ( mac ) , which is a microbial complex of mycobacterium avium and mycobacterium intracellulare .\nthere have been many reports concerning its radiologic findings.123 ) although uncommon , several cases of solitary pulmonary nodules ( spn ) caused by mac pulmonary infections have been reported,456 ) which is different from the typical presentation of mac .\nhowever , a case of a multiple cavitating nodular infection with neither a fibrotic change nor nodular bronchiectasis associated with m. intracellulare has not been reported .\nwe present the case of a 67-year - old asian woman who had a m. intracellulare infection presenting with multiple cavitating pulmonary nodules , which was differentiated from metastatic lung disease by percutaneous transthoracic needle aspiration ( pcna ) .\nshe presented to a local clinic after a single occurrence of hemoptysis 10 days prior .\nthe color of the hemoptysis was scarlet and the amount was 1/2 cup of soju , korean distilled spirits .\nshe had been diagnosed with type 2 diabetes mellitus ( dm ) 2 years prior at a local clinic , and had since been taking metformin 500 mg after breakfast and dinner .\nglycosylated hemoglobin was 6.7% , and she had good control of her blood sugar levels during hospitalization .\nafter a chest ct was obtained at the local clinic , she was transferred to our hospital to investigate the multiple cavitary pulmonary nodules that were found on the ct scan .\nwhen the patient visited our hospital , her initial vital signs showed a blood pressure of 110/70 mm hg , heart rate of 80 beats / min , respiratory rate of 16 breaths / min , and body temperature of 36.8. both pupil responses to light were normal and there was no abnormality in the conjunctivae and sclerae .\non auscultation , neither crackles nor wheezing was heard in both lung fields , and the heart sound was regular without murmur .\nat the first visit to our hospital , the patient did not have any symptoms .\nthere were several round nodules in both the upper lung zone and right middle lung zone , and patch consolidation in the left lower lung zone on the chest radiography , which is suggestive of mycobacterium tuberculosis ( mtb ) or metastatic lung disease ( figure 1 ) .\nsimilarly , the chest ct showed centrilobular nodules with a tree - in - bud appearance and three round cavitary nodules in the left apex , the right upper lobe posterior segment , and the right lower lobe superior segment , suggestive of mtb or metastatic lung disease ( figure 2 ) .\nwe isolated the patient because we could not exclude the possibility of mtb along with metastatic lung disease .\nthe initial laboratory parameters were as follows : total leukocyte count 7,500/mm ( neutrophil 64.6% , lymphocyte 21.1% , monocyte 0.44% ) ; hemoglobin level 12.8 g / dl ; and platelet count 217,000/mm .\nthe level of c - reactive protein was 0.03 mg / dl and other parameters were within the normal limit on the blood chemistry tests .\nadditionally , the coagulation profile was checked , and the prothrombin time was 11.1 seconds ( international normalized ratio 1.35 ) .\nfor further evaluation , we planned to perform a bronchoscopy and pcna , and the additional imaging examinations were not performed because chest imaging was obtained on the day of the initial hospital visit .\nthe results of three smears for acid - fast bacilli , and a nucleic acid amplification test for mtb and ntm in sputum were all negative . for further evaluation ,\na bronchoscopy was performed on the left upper lobe apical segmental bronchus , the right upper lobe posterior segmental bronchus , and the right lower lobe superior segmental bronchus .\nthe smear test of the bronchoscopic washing fluid was positive for acid - fast bacilli .\nthe result of nucleic acid amplification was negative for mtb , but positive for ntm .\ntherefore , the patient was diagnosed with ntm , so the patient 's quarantine was lifted .\nafter 7 days , heavy colonies with confluent growth in ogawa 's egg medium were detected in the bronchial washing fluid culture .\nafter 2 weeks , several colonies with confluent growth in the mycobacterium growth indicator tube 's egg medium were detected in the bronchial washing fluid culture .\nthe precise species was identified using a polymerase chain reaction - restriction fragment length polymorphism - based method that identified differences in the rpob gene.7 ) the colonies were subsequently identified as m. intracellulare . to rule out metastatic lung disease ,\nthe lung tissue from the biospy showed chronic granulomatous inflammation with caseating necrosis ( figure 3a , b ) .\nfor further evaluation , a nucleic acid amplification for mtb and ntm with a stain for acid - fast bacilli was conducted using tissue from the pcna .\nthe additional report showed that both the nucleic acid amplication for ntm and the stain for acid - fast bacilli were positive ( figure 3c ) , and there were no malignant cells .\nthis finding was consistent with ntm infection , and we could exclude metastatic lung disease . in conclusion ,\nthe lung tissue from the biospy confirmed the diagnosis obtained from the bronchial washing fluid culture . with the diagnosis of ntm infection\nthe patient was prescribed a medication regimen that included rifampin ( 450 mg ) , ethambutol ( 800 mg ) , and clarithromycin ( 1,000 mg ) . a drug susceptibility test for clarithromycin\nwas performed , and the result showed that the m. intracellulare was sensitive to clarithromycin .\nthe patient started to complain of nausea and vomiting , and had poor oral intake 7 days after taking the medication for ntm .\nwe changed the time for taking the medication from before meals to before bed , after which her symptoms improved .\nthere were no other complications such as an abnormal liver function test or optic neuritis .\nwe have performed blood tests and chest radiography to monitor the side effects and the disease progression .\nm. avium is the more important pathogen in a disseminated disease , whereas m. intracellulare is the more common respiratory pathogen .\nthe chest radiography and ct scans showed abnormalities typical of the two forms of mac lung disease .\nthe traditionally recognized presentation of mac lung disease is as an apical fibrocavitary lung disease with large cavities , located in the upper lobe .\nthis form of the disease usually occurs in men with a history of cigarette smoking , excessive alcohol use , and underlying lung disease in their late 40s and early 50s . if not treated , this form of mac is rapidly progressive within a relatively short time period , 1 to 2 years\nmac lung disease also presents with bronchiectatic nodular infiltrates , usually involving the right middle lobe or the lingula segment , predominantly in postmenopausal and non - smoking women .\nthis form of the disease has a tendency to progress much slower than the fibrocavitary disease , therefore long - term follow - ups lasting from months to years may be necessary to determine clinical or radiographic changes . in this indolent form of the disease\nspn is identified as focal , round , or oval areas of increased opacity in the lung that measure 3 cm in diameter .\nthese nodules are frequently discovered incidently on chest radiography or chest ct.8 ) spn is often assumed to be attributable to mtb infection.9 ) however , it has been shown in case reports that spn can be attributable to mac lung infection.456 ) in 2009 , sekine et al.10 ) reported a case of a mac pulmonary infection presenting with multiple nodules , which was an unusual presentation of a mac pulmonary infection . unlike mtb\ntherefore , the isolation of mac species from a respiratory sample is not sufficient evidence of ntm lung disease . in 1997 , the american thoracic society issued a revised set of diagnostic criteria for ntm pulmonary disease . according to these criteria ,\na patient with ntm lung disease must have compatible symptoms and signs , and a compatible chest radiography or chest ct abnormalities .\nthe current case did not strictly satisfy the diagnostic criteria proposed by the american thoracic society in terms of radiographic findings .\nthe diagnostic criteria of ntm lung disease must be expanded to such cases of spn , multiple nodules , and multiple cavitary nodules , as in our case . in our case , we could not initially rule out mtb lung infection due to the chest ct findings , which showed multiple cavitating nodules with centrinodular nodules .\nwe did not suspect mac lung infection because there was neither bronchiectasis in the right upper lobe or the left lingular segment nor a fibrotic change in the upper lobe .\nwhile the bronchoscopy findings were sufficient to diagnose the patient with mac lung infection , we also conducted a pcna to rule out metastatic lung disease .\n, we differentiated the atypical presentation of mac lung infection from mtb lung disease or metastatic lung disease .\nntm have emerged as an increasingly important pathogen in the last two decades . in korea ,\nthere has been an increasing prevalence of mac infections , and an increasing number of cases presenting with atypical findings .\nour case report highlights the importance of differentiating among mtb , mac infection , and metastatic lung disease in cases of multiple cavitary nodules .\nclinicians should consider the possibility of mac lung infection with various findings on chest radiography and chest ct .\nwe believe that pcna can be a valuable diagnostic tool for differentiating mtb and mac , and differentiating between malignant diseases and infectious diseases when a pulmonary nodule is revealed on chest radiography or chest ct scans . in conclusion , to the best of our knowledge , this is a very rare report of a mac pulmonary infection presenting with multiple cavitary nodules . as the prevalence of mac infections increases , more cases start to show atypical radiographic findings , compared to the typical apical fibrocavitary or bronchiectatic nodular forms . other forms of mac have been reported , such as spn and multiple nodules . in this report , we present another form of mac pulmonary infection .\ntherefore , clinicians should consider the possibility of mac lung disease with various findings on chest radiography or chest ct scans .\nin addition , pcna can be a useful diagnostic tool for evaluating multiple nodules to differentiate metastatic lung diseases from infectious diseases such as mtb or mac lung infections .", "answer": "nontuberculous mycobacteria ( ntm ) have been increasingly recognized as an important cause of chronic pulmonary infections . \n the mycobacterium avium complex ( mac ) , which is composed of two species , mycobacterium avium and mycobacterium intracelluare , is the most commonly encountered pathogen associated with ntm lung disease . mac pulmonary infection typically presents in a fibrocavitary form or a nodular bronchiectatic form . \n however , there have been atypical presentations of mac pulmonary infections , including solitary pulmonary nodules ( spn ) . \n there have been several previous reports of spn due to mac infection in the united states , japan , and korea . in 2009 , \n sekine and colleagues reported a case of mac pulmonary infection presenting with multiple nodules . to date , however , there have been no cases of ntm lung infection with multiple cavitary pulmonary nodules , and neither a fibrotic change nor nodular bronchiectasis . \n the present case showed a multiple cavitating nodular lung infection due to mac , which is very rare and different from the typical presentation of mac pulmonary infections . \n we also showed that percutaneous transthoracic needle aspiration can be a useful diagnostic tool to evaluate a case of multiple cavitary nodules .", "id": 580} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfailure of a total knee arthroplasty ( tka ) is often associated with loss of bone from either the proximal aspect of tibia or the distal aspect of the femur .\nthese defects are usually classified as contained or uncontained.1 the reconstruction of large uncontained defects represents a major challenge to the revision surgeon .\noptions for reconstruction2 of large defects include metal augments , custom prostheses , massive autogenous bone - grafts and massive allografts .\nmetal augments are recommended only for small to medium sized defects in elderly low demand patients .\ncustom prostheses are costly , time consuming to manufacture and may not fit as well as planned or at all at the time of surgery .\nautogenous bone - grafting is not suitable for large defects or in situations where structural support is required .\nallografts provide a biological solution , have the advantage of easy fashioning to fit irregular defects , restore bone stock and have relatively low cost .\nuse of femoral head allograft , complete distal femur or proximal femur allograft has been reported in some studies34 ; however , no study has reported use of both distal femur and proximal tibia allograft in a single revision total knee arthroplasty .\nwe report the first successful use of both complete distal femoral and proximal tibia massive allografts in the reconstruction of large femoral and tibial uncontained defects during revision total knee arthroplasty .\na 70-year - old male patient , farmer by occupation , presented with a swollen , painful and unstable right knee with primary complaint of inability to bear weight .\npassive range of motion was painful and limited to 10 degrees of hyperextension to 50 degrees of flexion in april 2005 .\nthe patient also had a periprosthetic supracondylar fracture of femur following a trivial fall , for which open reduction and internal fixation was done elsewhere eight years back with condylar blade plate .\nthe skin revealed thick scar tissue on both anterior and lateral aspects of the knee due to secondary wound healing after previous surgeries .\nanteroposterior and lateral radiographs [ figure 1 ] revealed severe osteolytic bone defects on femoral and tibial aspects along with primary total knee prosthesis and condylar blade plate in situ .\ninfection was ruled out preoperatively with bone scan and laboratory markers ( erythrocyte sedimentation rate , c- reactive protein ) .\nwe decided to reconstruct the knee with structural distal femur and proximal tibia allografts and constrained fixed - bearing revision knee prosthesis ( nexgen , lcck , zimmer , warsaw ) .\nanteroposterior and lateral x - rays of right knee showing extensive osteolysis on both femoral and tibial aspects we used the previous midline incision and a medial parapatellar approach .\nwe removed much necrotic , granulomatous tissue ( biopsy proven ) which usually occurs due to extensive polyethylene wear .\nafter debridement , the whole proximal tibia [ figure 2 ] presented a massive uncontained defect , classified as type iii according to anderson orthopaedic research institute classification.5 the whole distal femur also presented a large uncontained type iii bone defect involving both medial and lateral femoral condyles [ figure 2 ] .\nhowever , femoral attachment of lateral collateral ligament was deficient , and ligament was identified with a piece of bone .\nthe intraoperative photograph shows the defect after thorough debridement both proximal tibial and distal femoral cadaveric allografts [ figure 3 ] with a diameter smaller than that of the host bone were selected so that they could be placed within the host cortical shell .\nthe allografts were taken from our own cadaveric bone bank , where they underwent radiation with 2.5 megarads and were stored at 70c .\ntwo surgical teams were used during the management of the case , for optimal efficiency .\none team prepared the allograft , making appropriate femoral cuts and cementing in a long - stemmed revision femoral component .\ncultures were taken from the knee as well as the allograft to rule out any existing infection .\nstep - cut prepared distal femoral and proximal tibial allografts both the recipient distal femur and proximal tibia were step - cut with minimal bone resection .\non the side table , step - cut was made in both allografts to match that of the host bone and instrumented with trial implants .\nthe implant allograft composite was put for trial in situ , and the cuts were fine tuned as required .\nthe revision knee components were cemented [ figure 4 ] on the back - table into the distal femoral and proximal tibial allografts with a long stem .\ncare was taken during cementing to avoid getting cement on the interface between the graft and the host .\nonce the cement had set , the construct was implanted with full assembly , matching the two step - cuts .\nthe residual host femur , with its ligaments and other soft tissues attached , was wrapped around the allograft host junction to serve as a living bone graft [ figure 5 ] .\nextensor mechanism alignment and tracking was checked , and the wound was closed in layers . fully prepared composite allograft with lcck implant intraoperative photograph showing invagination of composite allografts into host bone prophylactic antibiotics consisted of an intravenous first - generation cephalosporin for five days , followed by oral antibiotics for seven days .\npartial weight bearing was allowed at four weeks , and full weight bearing was started after eight months when there was radiographic evidence of union on both sides .\nno wound complication was noted during the entire follow up . at the end of five years of\nfollow up ( i.e. , in april 2010 ) , the patient was walking full weight bearing and had complete incorporation of allograft and host bone with no signs of osteolysis [ figure 6 ] .\nhis active range of motion range of motion ( rom ) was 0 - 110 degrees .\nanteroposterior and lateral x - rays of the same patient at five - year follow - up showing good allograft incorporation\nwe removed much necrotic , granulomatous tissue ( biopsy proven ) which usually occurs due to extensive polyethylene wear .\nafter debridement , the whole proximal tibia [ figure 2 ] presented a massive uncontained defect , classified as type iii according to anderson orthopaedic research institute classification.5 the whole distal femur also presented a large uncontained type iii bone defect involving both medial and lateral femoral condyles [ figure 2 ] .\nhowever , femoral attachment of lateral collateral ligament was deficient , and ligament was identified with a piece of bone .\nthe intraoperative photograph shows the defect after thorough debridement both proximal tibial and distal femoral cadaveric allografts [ figure 3 ] with a diameter smaller than that of the host bone were selected so that they could be placed within the host cortical shell .\nthe allografts were taken from our own cadaveric bone bank , where they underwent radiation with 2.5 megarads and were stored at 70c .\ntwo surgical teams were used during the management of the case , for optimal efficiency .\none team prepared the allograft , making appropriate femoral cuts and cementing in a long - stemmed revision femoral component .\ncultures were taken from the knee as well as the allograft to rule out any existing infection .\nstep - cut prepared distal femoral and proximal tibial allografts both the recipient distal femur and proximal tibia were step - cut with minimal bone resection .\non the side table , step - cut was made in both allografts to match that of the host bone and instrumented with trial implants .\nthe implant allograft composite was put for trial in situ , and the cuts were fine tuned as required .\nthe revision knee components were cemented [ figure 4 ] on the back - table into the distal femoral and proximal tibial allografts with a long stem .\ncare was taken during cementing to avoid getting cement on the interface between the graft and the host .\nonce the cement had set , the construct was implanted with full assembly , matching the two step - cuts .\nthe residual host femur , with its ligaments and other soft tissues attached , was wrapped around the allograft host junction to serve as a living bone graft [ figure 5 ] .\nextensor mechanism alignment and tracking was checked , and the wound was closed in layers . fully prepared composite allograft with lcck implant intraoperative photograph showing invagination of composite allografts into host bone\nprophylactic antibiotics consisted of an intravenous first - generation cephalosporin for five days , followed by oral antibiotics for seven days\npartial weight bearing was allowed at four weeks , and full weight bearing was started after eight months when there was radiographic evidence of union on both sides .\nno wound complication was noted during the entire follow up . at the end of five years of\nfollow up ( i.e. , in april 2010 ) , the patient was walking full weight bearing and had complete incorporation of allograft and host bone with no signs of osteolysis [ figure 6 ] .\nhis active range of motion range of motion ( rom ) was 0 - 110 degrees .\nanteroposterior and lateral x - rays of the same patient at five - year follow - up showing good allograft incorporation\nfew options are available to the surgeon for reconstruction of massive bone defects surrounding a failed total knee arthroplasty ( tka ) .\nthe application of allografts in revision tka is an attractive option . the use of femoral head allografts for the management of large bone defects in revision tka has been reported .\nvery few studies have also reported using either massive distal femoral or proximal tibial allograft for large defect reconstruction in revision tka.34 our patient presented a unique problem , having severe bone loss on both femoral and tibial aspects . using both massive distal femoral and proximal tibial allografts proved to be a successful mode of treatment with distinct advantages . placing\nthe allograft within the vascularized host bone will add some structural support to the allograft and provide an environment by which the allograft may eventually incorporate .\none major concern with the use of allografts is the risk of infection . in a large series by lord et al.,6\nthe risk of infection with the use of small allografts ( femoral heads ) was negligible ; and with the use of larger allografts , acceptable ( 4%-5% ) .\nsome authors have recommended plate and screw fixation of the allograft in addition to invagination of the graft , to ensure rotational stability . using a stemmed component and avoiding\nthe use of plate fixation decreases the need for extensive soft tissue dissection , avoids weakening of the graft and may decrease the risk of infection by preserving the soft tissue envelope.7 another concern about the use of massive allografts is their performance in the long term , especially in view of reports showing resorption and failures of allografts used in revision total hip arthroplasty at longer follow ups .\nhowever , use of allografts in anatomically matching sites ( proximal tibia for proximal tibia , distal femur for distal femur ) allows for accurate orientation of trabeculae along the lines of stress .\nthis technique requires that the allograft is appropriately shaped for intussusception into the host bone with stable struts of host bone maximally contacting step - cuts in the graft.8 the limitation in terms of applicability of this study in practice could be the non - availability of such allografts at many centers .\nnewer trabecular metal wedges and sleeves may be an option ; however , they are very costly\n. these allografts are free for patients at our institute and provide a biological and effective alternative .\nthere should be a stimulus to establish more and more cadaveric allograft retrieval centers to deal with the complex and often neglected cases of bone loss , which is particularly common in the indian scenario .\nthe use of dual structural massive allografts provides a stable and durable reconstruction of this uncommon presentation with both femoral and tibial large bone deficiencies encountered during a revision tka . at a five - year follow - up\n, we did not find any infection , graft failure or loosening of implant , in spite of using two massive structural allografts in a single revision tka .\nfurther follow up with large number of patients is necessary to determine the long term fate of these allografts .", "answer": "the reconstruction of large uncontained defects represents a major challenge to the revision total knee surgeon , and the outcome of the revision often depends on the management of these bone deficiencies . \n we report the first successful use of both complete distal femoral and proximal tibia massive allografts in the reconstruction of large femoral and tibial uncontained defects during revision total knee arthroplasty . at the five - year follow up , \n we did not find any infection , graft failure or loosening of implant , in spite of using two massive structural allografts in a single revision total knee arthroplasty .", "id": 581} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nguillian barre syndrome ( gbs ) is associated in 45 - 75% of cases with cranial nerve involvement .\nfacial nerve is the commonest to be involved followed by extra ocular muscles and lower cranial nerve involvement .\nonly two cases has been reported till date with gbs with total paresis of motor cranial nerves . here\na thirteen year old boy presented with acute progressive areflexic flaccid quadriparesis associated with motor cranial nerve involvement with bilateral facial and bulbar weakness .\nhe had an upper respiratory infection one week preceding the motor weakness which started from the lower limbs . on day seven\nafter the onset of motor weakness of limbs , the child developed significant bulbar weakness , difficulty in talking and could not move the tongue .\nhe was totally anarthric . on day nine , he had significant respiratory muscle weakness requiring mechanical ventilatory support . on day fourteen ,\nthe nerve conduction studies ( ncs ) were suggestive of severe demyelinating motor sensory polyradiculoneuropathy .\nhis anti - ganglioside antibody panel in the blood showed positive igm gm2 , gt1b , igg gm1,2,3 and gt1b antibodies .\nhis csf showed albuminocytological dissociation and his antinuclear antibody was negative . his magnetic resonance image ( mri )\nhe was treated with intravenous immunoglobulin at a daily dose of 0.4 g / kg for five days .\nhe showed gradual improvement and started swallowing after eight weeks of the onset of illness .\nthe wasting of the tongue also improved gradually at 3 months after the onset of illness [ figure 2 ] . at 6 months\nrepeat ncs was suggestive of motor sensory demyelinating radiculoneuropathy with improvement in conduction velocities and compound muscle action potential amplitudes compared to baseline study .\ntongue wasting noted at 2 weeks after the onset of motor weakness improvement in tongue weakness and wasting noted at 6 months twelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs .\n, reported a case of fulminant gbs with quadriplegia and total paresis of motor cranial nerves and polo et al . , reported a case of atypical gbs with multiple cranial neuropathies including xii cranial nerve involvement\ntwelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs .\n, reported a case of fulminant gbs with quadriplegia and total paresis of motor cranial nerves and polo et al . , reported a case of atypical gbs with multiple cranial neuropathies including xii cranial nerve involvement\ngbs with multiple cranial nerve involvement is a known entity but the involvement of xii cranial nerve is extremely rare .\nour patient had multiple cranial neuropathies with involvement of vii , ix , x and xii nerves .\nhe had a severe form of gbs with areflexic quadriparesis along with respiratory muscle involvement requiring prolonged ventilatory support .\nhis mri brain was normal supporting that the tongue weakness is due to xii cranial nerve involvement .\ntwelfth nerve involvement , either isolated or as a part of multiple cranial nerve involvement is quite uncommon and only two cases has been reported till date as a part of multiple motor cranial nerve involvement in a case of gbs .\ntan et al . , reported a fulminant case of gbs with quadriparesis with all motor cranial nerve involvement and their ncs showed segmental demyelination which was responsible for such severe involvement and possibly the pathophysiology in this case and our case are similar .\ndescribed a 23 years gentleman who developed a progressive illness over ten days with diplopia , facial diplegia and a nasal voice .\nsubsequently , the patient also developed weakness of the neck and tongue muscles , dysphagia , abolition of reflexes of the left arm and right triceps but without involvement of the respiratory muscles or other limbs .\nhowever , the same patient had involvement of reflexes of left arm and right triceps only without involvement of respiratory muscles and lower limbs .\nhence it was thought to an atypical variant of gbs in contrast to our case where he had all the typical features of gbs .\nour patient showed anti - gm2 antibody positive which is usually seen in post cmv infection with or without gbs .\nusually going on to ventilatory support requirement and the same is found in our patient .\nthe two previous case reports did not have the autoantibody levels to corroborate the clinical and electrophysiological findings .\nthe cranial neuropathy in our patient showed gradual recovery and tongue atrophy recovered over next three months . at 6 months\ngbs with multiple cranial nerve involvement can rarely involve the xii nerve as well causing significant tongue weakness and such a presentation may be indicative of a severe nature of the disease and it usually recovers over a period of time .", "answer": "guillian barre syndrome ( gbs ) is associated with cranial nerve involvement . \n commonest cranial nerves involved were the facial and bulbar ( ixth and xth ) . \n involvement of twelfth cranial nerve is rare in gbs . \n we present a case of gbs in a thirteen years old boy who developed severe tongue weakness and wasting at two weeks after the onset of gbs . \n the wasting and weakness of tongue improved at three months of follow up . \n brief review of the literature about xiith cranial nerve involvement in gbs is discussed .", "id": 582} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nMerochlorins A\\xe2\\x80\\x93D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases\n\nPaper sections:\n\nThe molecular logic of biosynthetic halogenation has illuminated four oxidative enzyme families that deliver halogen ions to a diversity of organic scaffolds.1\u20133 Vanadium-dependent haloperoxidases (VHPOs) are rare bacterial halogenating enzymes that were first characterized from fungi and macroalgae where they catalyze the oxidative halogenation of electron-rich organic substrates.4,5 We recently showed that the napyradiomycin antibiotics6\u20138 are distinctive streptomycete meroterpenoids, whose linear isoprenoid side chains undergo intramolecular VHPO-mediated cyclization reactions.9,10 Herein, we report the discovery of a new natural product group of chlorinated meroterpenoid antibiotics, merochlorins A\u2013D (1\u20134, Figure 1), that we demonstrate through in vivo biosynthetic experiments are unique examples of VHPO-derived products.
During our screening campaign to find new anti-cancer and anti-infective agents from marine microorganisms, we isolated Streptomyces sp. strain CNH-189 from a marine sediment sample collected near Oceanside, California.11 We previously reported the discovery of the ansamycin polyketide ansalactam A from this strain,11 and more recently the preliminary characterization of the meroterpenoid antibiotic merochlorin A (1),12 which consists of a highly unusual bicyclo[2.2.1]-heptanone ring system and a propan-2-ylidenecyclopentane moiety. To unambiguously establish its absolute configuration, we solved the crystal structure of a methylated and acetylated derivative of 1 (Figure 1B).
Bioassay-guided fractionation of the crude organic extract of strain CNH-189 facilitated the isolation of two new merochlorin analogues, 2 and 3 (Figure 2). Notably, 1 and 2 are highly active against clinically relevant methicillin-resistant Staphylococcus aureus strains with MICs in the range of 2\u20134 \u03bcg/mL, whereas 3 showed only weak antibiotic properties (Table S4). High-resolution MS (HR-MS) and NMR spectral analysis allowed the complete structural assignment of merochlorins B (2) and C (3), which possess distinctive carbon skeletons unrelated to known natural products [Figure 1; Supporting Information (SI)]. Although 1 and 2 share the same molecular formula, C25H29ClO4, 2 has a unique 6-5-5-fused ring system, composed of dihydroxynaphthalenone and propan-2-ylidenecyclopentane moieties. We established the planar structure of 2 and the fusion of the unusually configured terpenoid residue with the naphthyl unit by extensive two-dimensional NMR spectroscopy. The relative configuration was further determined by interpretation of ROESY correlations as 8S*, 9R*, and 10S*.
The structure of 3, on the other hand, was clearly distinct from 1 and 2 based on its molecular formula of C26H32Cl2O5, containing additional carbon and chlorine atoms. HMBC correlation data not only revealed a different attachment of the terpenoid residue to the naphthyl unit at C-10, but also exposed a second attachment site through an ether linkage between C-19 and C-4 via four-bond correlation from the singlet methyl proton H-21 to C-14. The macrocyclized sesquiterpenoid residue is thus attached on both ends of the tetrahydronaphthoquinone core molecule (Figure 1). Although we established the relative configuration of C-9 and C-10 as 9R* and 10S*, we have not yet assigned the configuration of the isolated C-18 chloro group.
The unique structures of the merochlorins suggested that they are constructed via unusual biotransformations, possibly involving VHPO-dependent catalysis of a chloroetherification reaction similar to napyradiomycin formation.10 To gain access to the biosynthetic gene cluster, we subjected CNH-189 genomic DNA to short-read, paired-end Illumina sequencing. Targeted assembly of portions of the genome with homology to napyradiomycin biosynthesis (nap) genes yielded three contigs with significant sequence similarity to known meroterpenoid gene clusters (Figure S17).9,13\u201315 A 15.8-kb contig that contained a putative 1,3,6,8-tetrahydroxynaphthalene (THN, 5) synthase16,17 gene (mcl17) was found on fosmid 3D9 in a pCC1FOS-based genomic DNA library of strain CHN-189. We next replaced mcl17 with an apramycin resistance cassette in CNH-189 to link the isolated genes to merochlorin production.18 A comparison of culture extracts from CNH-189\u0394mcl17 and the wild-type strain by HPLC showed that the mutant was unable to produce merochlorins 1\u20133 (Figure 2). This confirmed that the THN synthase, encoded by mcl17, is essential for merochlorin production and that the genes identified on fosmid 3D9 likely represent part of the merochlorin biosynthetic gene cluster.
We obtained the complete gene cluster (57.6 kb, Figure 3) from total sequencing of 3D9, isolation of overlapping fosmids, and primer walking. Forty-one open reading frames (ORFs), mcl1\u201341, were assigned to the cluster and attributed to biosynthetic, resistance, transport, and regulatory functions (Table S6). Several genes have sequence homology to genes from other meroterpenoid clusters, such as mcl2\u2013mcl9 that putatively encode the mevalonate pathway for isoprene biosynthesis;19mcl18, a putative THN monooxygenase gene;20mcl21, a putative methyltransferase gene; and mcl23, a putative aromatic prenyltransferase gene.21 In addition, the mcl cluster includes numerous structural genes that are unprecedented in meroterpenoid clusters, e.g., a putative polyprenyl synthase, mcl22, and a putative iron\u2013sulfur cluster-containing protein, mcl30. Intriguingly, two genes, mcl24 and mcl40, were found to be highly homologous to the nap VHPO genes (Table S6).9
Based on the bioinformatic analysis of the mcl cluster, we concluded that most of the unique biosynthetic capacity for merochlorin production was encoded on fosmid 3D9, except for the putative VHPO Mcl40 (Figure 3). To investigate whether the genes found on 3D9 are sufficient for the formation of the merochlorins and to explore the role of mcl40, we expressed the fosmid heterologously in the genome minimized strain, Streptomyces coelicolor M1154.22 Therefore, 3D9 was redesigned for stable integration into Streptomyces chromosomes via attB/attP-site-specific recombination.23 Culture extracts of the generated S. coelicolor M1154/merLK01 strain were analyzed by HPLC-MS.
Compounds 1 and 2 were accumulated by the mutant, but 3 was not produced (Figures 2, S18). However, we observed a previously unrecognized metabolite, merochlorin D (4). HPLC chromatographic comparison with the CNH-189 wild-type strain also revealed the production of 4 (Figure 2). To obtain sufficient quantities of 4 for structure elucidation, we optimized the culture conditions of CNH-189 to yield approximately 5 mg/L. HR-MS and NMR spectral analysis revealed that 4 was structurally similar to 3, except for the presence of an olefinic proton at C-18 and only one chlorine atom instead of two (Figure 1A). HMBC correlation data confirmed the dimethyl terminal olefin unit, and ROESY data gave the same relative configuration as in 3. Thus, the heterologous pathway expression showed that a 36-kb fragment of the 57.6-kb gene cluster encodes all of the enzymes required for the biosynthesis of 1, 2, and 4. However, the absence of 3 in the mutant extract suggested that one or more essential genes required for its formation are missing on fosmid 3D9. We speculate that 4 is a direct precursor to 3 and that the VHPO Mcl40 may catalyze the unprecedented macromolecular chlorination\u2013cyclization reaction to give the 15-membered ring. In the biosynthesis of the napyradiomycins, NapH1 supports a chloronium-assisted stereoselective cyclization to yield a 6-membered ring, harboring a chlorinated gem-dimethyl ether.10 Similarly, the putative VHPO Mcl40 might use 4 or a less substituted derivative as a substrate to afford the massive 15-membered cyclic ether ring in 3.
To explore whether Mcl40 can indeed support the biosynthesis of 3, we heterologously expressed fosmid clone 6B10, which contains a larger portion of the mcl locus and includes mcl40 (Figure 3). HPLC-MS analysis of the resulting S. coelicolor M1152/merLK30 strain revealed the production of all natural merochlorins, including 3 (Figure 4), suggesting that Mcl40 is involved in the chloronium-assisted macrocyclization of 4 to 3 (Figure 1A). However, the production yields of 3 and 4 were significantly lower compared with the original fosmid clone 3D9, which produced 4 but not 3. We speculate that the loss of the mcl12/13 genes of unknown function in 6B10 may lead to the observed lower merochlorin production levels. With respect to the second homologous VHPO in the mcl cluster, Mcl24, we hypothesize that it may catalyze a chlorination step of an early pathway intermediate to install the polyketide chlorine atom that can be found on all characterized merochlorin molecules.
Although 1\u20134 have different molecular architectures, they share common structural features, suggesting that they may also share early biosynthetic intermediates (Figure 1A). For example, the aromatic portion of 1\u20134 is likely derived from THN, similar to other hybrid polyketide\u2013terpenoid metabolites.16 Thus, we propose that THN is the general precursor for two distinct metabolic pathways. The first pathway may proceed through prenylation, chlorination, and two divergent cyclization reactions to produce 1 and 2. The second pathway would generate 3 and 4 and may involve oxidation, methylation, prenylation, and two chlorination reactions. The order of the proposed biotransformations as outlined in Figure 1 is speculative and serves as a model for interrogating the function of merochlorin biosynthetic enzymes that may catalyze new interesting biochemical reactions. This divergent pathway that we propose represents a rare example where a single gene cluster encodes the formation of several architecturally unique metabolites.24
The merochlorins appear to be constructed with the same, rearranged C15-isoprene unit. To the best of our knowledge, the sesquilavandulyl carbon skeleton is unprecedented in bacteria. However, this type of skeleton has been infrequently encountered in plant natural products such as the xanthane roeperanone from Hypericum roeperanu.25 The prenylation substrate may be a preformed sesquilavandulyl diphosphate generated by Mcl22, that shows sequence similarity to undecaprenyl diphosphate synthase. Alternatively, the isoprenoid moiety may simply be formed by the sequential addition of dimethylallyl and geranyl units to a THN-based intermediate.
Only one putative prenyltransferase, Mcl23, is encoded in the mcl cluster. Merochlorins A/B and C/D are likely prenylated at two different positions, suggesting that Mcl23 catalyzes the prenylation at two adjacent carbon atoms at C-8 to give 1 and 2 and at C-10 to furnish 3 and 4 (the carbon atom numbering scheme adopted for the final natural product, Figure 1A). The oxidation state of THN (Figure 1A, 5) supports prenylation at C-4 to give an intermediate that can lead to 1 and 2. However, the same oxidation state does not allow C-3 alkylation to produce 3 and 4. We therefore propose that 5 is first partially oxidized by Mcl18 to the flaviolin hydroquinone, or directly to flaviolin followed by reduction, to produce an intermediate that is activated for alkylation at the C-3 position, which ultimately provides 3.
The genetic basis for the terpene cyclizations involved in the biosynthesis of 1 and 2 remains highly speculative. Notably, homologues to known terpene cyclases are not encoded in the cluster. We hypothesize that the internal olefin on the sesquiterpene attached to 5 undergoes epoxidation or halogenation, activating the molecule for an intramolecular cyclization. Nucleophilic attack by a carbon to form a C\u2013C bond would lead to 1, whereas nucleophilic attack by oxygen to form a C\u2013O bond would lead to 2 (Figure 1A, Paths a and b). In both scenarios, a second cyclization event would follow with concomitant elimination of water or HCl to yield 1 and 2. Because both VHPOs seem to be involved in chlorination reactions, we suspect that an oxidative transformation is more likely to occur in the final steps of 1 and 2 biosynthesis.
In conclusion, we discovered the merochlorins as new streptomycete antibiotics with diverse molecular architectures that derive from a novel pathway involving polyketide and terpenoid biochemistry. Our in vivo biosynthetic results established the genetic basis for merochlorin construction and support the involvement of just the second example of VHPOs in bacterial natural product assembly.
", "answer": "Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures of four new meroterpenoid antibiotics, merochlorins A\\xe2\\x80\\x93D, produced by the marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis and heterologous biosynthesis in the genome-minimized model actinomycete Streptomyces coelicolor provided a 57.6 kb gene cluster that contains two genes encoding rare bacterial vanadium-dependent haloperoxidase (VHPO) genes. Pathway expression of two different fosmid clones that differ largely by the presence or absence of the VHPO gene mcl40, resulted in the differential biosynthesis of merochlorin C, suggesting that Mcl40 catalyzes an unprecedented 15-membered chloronium-induced macrocyclization reaction converting merochlorin D to merochlorin C.", "id": 583} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhowever , the iron overload in various organs leads to serious problems such as metabolic , endocrine , and growth abnormalities in such patients despite the expanded use of iron - chelator drugs ( 3 - 5 ) . patients with thalassemia intermedia ( ti )\nalthough the rate of iron loading is slower in ti than in tm , patients with ti can eventually develop complications similar to those of the patients with tm , including hepatic , endocrine and cardiac dysfunction ( 6 ) .\nmoreover , in patients with transfusion independent thalassemia , serum ferritin was a poor predictor of liver iron concentration ; therefore , chelation therapy may be postponed in patients with ti ( 7 ) .\nhepcidin is a small peptid hormone secreted by hepatocytes to regulate plasma iron concentration and distribution in different tissues ( 8 , 9 ) .\nchronic excess of hepcidin causes iron restricted anemia ( 9 ) , while the hepcidin deficiency leads to iron overload with iron deposition in the liver and parenchyma ( 10 ) .\nincreased plasma and stored iron stimulate hepcidin production , which in turn blocks dietary iron absorption and consequently iron loading .conversely , hepcidin is suppressed in iron deficiency ( 11 ) .\nhepcidin concentration is significantly higher in chronically transfused patients than in non - transfused ones , presumably due to iron overload ( 12 - 16 ) . despite using iron chelatorin patients with thalassemia ,\niron overload is one of the main mortality factors in such patients and hepcidin targeted therapeutics can help with better management of iron overload in patients with thalassemia ( 17 ) .\nthe current study aimed to determine the correlation between serum ferritin and hepcidin levels in patients with tm and ti , also compare serum hepcidin and ferritin levels between the two groups of patients .\nthe current cross - sectional study was conducted in hematology research center of shiraz university of medical sciences , shiraz , iran , in 2013 .\nthe study subjects included 90 patients , 50 tm and 40 ti , selected by systematic random sampling from the 500 tm and 280 ti patients registered at the thalassemia clinic of tertiary state hospital affiliated to shiraz university of medical sciences .\nthis is a referral center with 45 beds for patients with thalassemia in southern iran .\nthis study was approved by medical ethics committee of shiraz university of medical sciences ( grant number : 3652 , approval date : 21.03.2011 ) .\nthe diagnosis of thalassemia was based on complete blood count ( cbc ) , hb electrophoresis and clinical history . in the tm group ,\nblood transfusion had been started before two years old and all of them were on regular blood transfusion every - two to four weeks . in the tm group ,\ninclusion criteria were age above 10 years old , under regular follow up and regular blood transfusion , and iron chelation therapy . in the ti group ,\ninclusion criteria were transfusion independence and taking hydroxyurea ( hu ) 10 - 15 mg / kg / day for a duration of at least ten years .\npatients with the history of any recent infection or surgery , congestive heart and liver failures as well as positive viral hepatitis were excluded from the study .\na 2.5 ml sample of venous blood withdrawn from each participant was added to the tubes containing clot activator .\nplasma centrifuge was done immediately and 2 ml serum was separated and preserved at -20c , then carried by cold box to the laboratory to check serum hepcidin and ferritin levels .\nalso , 2 ml sample of venous blood was withdrawn from each patient and added to the tubes of cbc containing ethylenediamine tetraacetic acid edta anti - coagulant .\ncomplete blood count test was performed immediately with peripheral blood smears and then stained with wright stain and the rate of nucleated red blood cells ( nrbc ) per 100 white blood cells ( wbc ) was counted .\nfasting serum ferritin was checked by enzyme linked fluorescent assay elfa method , using mini vidas ( biomerievx s.a , france ) machine , and hepcidin was measured by enzyme linked immunosorbent assay elisa method ( competitive assay ) , using elisa reader dynex ( usa ) machine with drg hepcidin kit ( eia 4 705 ) . according to the direction of hepcidin kit manufacturer , the normal range of hepcidin in 5% - 95% of people with the age range of 23 to 67 years\nis from 13.3 to 54.4 ng / ml . the normal range of ferritin was considered as 20 - 300 g / lin males 10 - 100\ng / l in females before menopause , 20 - 200 g / l in females after menopause and 150 - 500\ntest of normality was done by shapiro - wilk test . among all the evaluated variables , only age had normal distribution .\ndescriptive data were summarized as mean and standard deviation , as well as median and interquartile range ( iqr ) , where appropriate .\ncorrelation between serum hepcidin and quantitative variables in each of the two groups of patients with tm and ti was evaluated by spearman correlation test .\nquantitative data between the two groups of patients were compared by student t - test and mann - whitney test .\nconsidering the correlation coefficient of 0.68 for urinary hepcidin and serum ferritin levels reported by origa et al .\n( 14 ) in 44 patients with thalassemia including 22 tm and 22 ti , = 0.05 and = 0.01 , the sample size was estimated as 29 patients in each group . for higher accuracy , sample size\ntest of normality was done by shapiro - wilk test . among all the evaluated variables , only age had normal distribution .\ndescriptive data were summarized as mean and standard deviation , as well as median and interquartile range ( iqr ) , where appropriate .\ncorrelation between serum hepcidin and quantitative variables in each of the two groups of patients with tm and ti was evaluated by spearman correlation test .\nquantitative data between the two groups of patients were compared by student t - test and mann - whitney test .\nconsidering the correlation coefficient of 0.68 for urinary hepcidin and serum ferritin levels reported by origa et al .\n( 14 ) in 44 patients with thalassemia including 22 tm and 22 ti , = 0.05 and = 0.01 , the sample size was estimated as 29 patients in each group . for higher accuracy ,\nthe mean age of the patients with tm and ti were 21.4 6.1(from 11 to 33 years ) and 23.7 6.1 years ( from 8 to 38 years old ) respectively , and there was no statistically significant difference between the two groups ( p = 0.076 ) .\nconsidering gender distributions , 21 ( 43.8% ) and 22 ( 55% ) of the subjects in the tm and ti groups were female , respectively ; there was no statistically significant difference ( p = 0.392 ) .\nthe median iqr for serum hepcidin levels were significantly higher in the tm compared to ti group ( 87.6 , 43.9 vs. 51.8 , 23.4 , p < 0.001 ) .\nin addition , the median iqr for serum ferritin levels were 2208 ( 3761 ) , and 465 ( 632 ) in the tm and ti groups respectively ; the difference was statistically significant ( p < 0.001 ) ( table 1 ) .\ntable 2 indicates the results of correlation between serum hepcidin levels and the evaluated parameters for the subjects with tm and ti .\nno statistically significant correlations were found between serum hepcidin with any of the evaluated variables in the two groups . also there were no statistically significant differences in serum hepcidin levels between males and females in patients with tm and ti ( p = 0.107 and p = 0.861 respectively ) .\nconsidering the cut - off point of 54.4 ng / ml for serum hepcidin levels , 44 ( 91.7% ) , and 18 ( 45% ) subjects had hepcidin levels higher than normal range in the tm and ti groups , respectively ( p < 0.001 ) . \nabbreviations : iqr , interquartile range ; sd , standard deviation ; nrbc , nucleated red blood cells ; wbc , white blood cell . \ndata are presented as mean sd , median ( iqr ) or male / female . \ndata are presented for n = 40 . statistically significant . in thalassemia major , it was pre - transfusion hemoglobin abbreviations : nrbc , nucleated red blood cells ; rs , spearman s rho correlation coefficient ; ti , thalassemia intermedia ; tm , thalassemia major ; wbc , white blood cell . in thalassemia major , it was pre - transfusion hemoglobin . \ndetermining hepcidin concentrations in subjects with iron - loading anemias may be useful to identify the patients at higher risk of iron toxicity due to severely decreased hepcidin levels ( 17 ) .\nbased on the current study results , 91.7% of the subjects with tm had serum hepcidin levels above normal compared to the patients with ti , 45% .\nalso , the median of serum hepcidin levels were significantly higher in the tm compared to ti group that was similar to those of the previous studies ( 14 ) . in iron loading anemias not treated by frequent transfusions , such as beta thalassemia intermedia and congenital dyserythropoietic anemias , urinary and serum hepcidin decrease due to high erythroid signals .\nhepcidin deficiency in turn allows excessive iron absorption and development of systemic iron overload ( 12 - 14 , 18 ) .\nalso , it could be due to more iron overload resulted from regular blood transfusion in the patients with tm compared to ti .\nas observed in the current study , ferritin levels were significantly higher in the subjects with tm .\nhemoglobin levels were significantly lower in the subjects with tm than in ti , which may be due to the time of blood sampling in the subjects with tm , immediately before transfusion . during transfusion intervals ,\nit is known that in patients with ti , there is also increased risk of iron over load due to increased intestinal iron absorption triggered by chronic anemia , ineffective erythropoiesis and decreased serum hepcidin ( 19 , 20 ) .\nthe current study showed higher erythropoietic activity in the subjects with ti than tm , since the median value for nrbc was significantly higher in ti compared to tm group . in ti group , since all subjects were on hu therapy for a long time , erythropoietic activity was expected to be suppressed and consequently hepcidin level was expected to be higher .\nbut it did not occur and it seems that hu at a dose of 10 - 15 mg / kg / day was not enough to suppress bone marrow activity and make erythropoiesis ineffective . however , previous reports documented that hu with the same dose was effective in decrease or cessation of the need for regular blood transfusion , as well as increasing hb levels in the patients with thalassemia ( 21 - 24 ) .\nthe current study showed no significant correlation between serum hepcidin and ferritin levels as a marker of iron overload in any of the tm or ti groups .\nthis result was in accordance with the previous reports that demonstrated the dominant role of erythropoiesis compared to iron overload in regulation of hepcidin in patients with thalassemia ( 25 - 27 ) .\n( 15 ) , the current study found no statistically significant correlation between hepcidin and pre - transfusion hemoglobin levels in tm patients . in a longitudinal study on 31 patients with tm\n. the strong point of the current study was large sample size compared to those of the previous reports ; however , there were some limitations in the study , since molecular erythropoietic activity was nit evaluated . in conclusion , based on the current study results\n, there was insignificant correlation between serum hepcidin and ferritin levels as a marker of iron overload in any of the two groups of patients with tm and ti , which supported the results of previous studies that regulation of hepcidin in patients with thalassemia is more affected by erythropoeitic activity than by iron overload .\nalso serum hepcidin levels were significantly higher in the tm than in ti group , which could mainly result from higher erythropoeitic activity in ti . in the subjects with ti\n, it is believed that low dose hu ( 10 - 15 mg / kg / day ) therapy for a long time could increase hb levels and lead to transfusion - independence , but probably not high enough to suppress bone marrow activity and make erythropoiesisin effective .\nincreased awareness of hepcidin levels in the patients with thalassemia could be helpful to diagnose and manage iron burden in such patients .", "answer": "background : hepcidin is a key regulator of iron absorption in humans \n . it is mainly affected by hypoxia and iron stores.objectives:the current study aimed to determine the correlation between serum hepcidin and ferritin levels in patients with thalassemia major ( tm ) and thalassemia intermedia ( ti).patients and methods : the current cross - sectional study investigated 88 randomly selected patients with thalassemia , 48 tm and 40 ti , registered at the thalassemia clinic of shiraz university of medical sciences , a referral center for thalassemia in southern iran in 2013 . \n all patients with ti were receiving hydroxyurea ( hu ) 10 - 15 mg / kg / day for at least 10 years . \n the serum hepcidin , ferritin levels , hemoglobin ( hb ) and nucleated red blood cell ( rbc ) of the two groups were measured.results:no statistically significant correlation was observed between serum hepcidin and ferritin levels in any of the two groups of patients with tm ( rs = 0.02 , p = 0.892 ) or ti ( rs = 0.055 , p = 0.734 ) . \n the median interquartile range ( iqr ) for serum hepcidin and ferritin levels were significantly higher in tm compared to ti group , ( hepcidin : 87.6 ( 43.9 ) vs. 51.8 ( 23.4 ) , p < 0.001 ; ferritin : 2208 ( 3761 ) vs. 465 ( 632 ) , p \n < 0.001).conclusions : there was insignificant correlation between serum hepcidin and ferritin levels in the two groups of patients with tm and ti . \n it seems that regulation of hepcidin in patients with thalassemia is more affected by erythropoeitic activity than iron stores . also , hepcidin levels were significantly higher in patients with tm than ti , possibly due to higher erythropoeitic activity in ti . \n in ti , it seems that low dose hu increases hb levels and leads to transfusion - independence , but it is not high enough to suppress bone marrow activity and ineffective erythropoiesis . \n consequently , serum hepcidin level decreases .", "id": 584} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nDynamic Presentation of Immobilized Ligands Regulated through Biomolecular Recognition\n\nPaper sections:\n\nUsing engineered materials to recapitulate the essential spatial and temporal characteristics of natural extracellular microenvironments during animal development is the key to successfully guiding cell behavior and fate selection in tissue engineering.1\u20136 However, it has remained a challenge to mimic the dynamic regulation of signaling ligands immobilized on extracellular matrices or on the surfaces of neighboring cells. Although soluble ligands can be added or removed readily during in vitro studies, the soluble form of a ligand that performs its function in an immobilized state in vivo potentially has opposite and detrimental effects because of competitive binding for cell surface receptors. This has been demonstrated by inhibition of Notch signaling in the presence of non-immobilized Notch ligands and death of anchorage-dependent cells in the presence of soluble RGD peptide.7\u20139 In recent years, materials capable of dynamically presenting immobilized bioactive ligands to cell surface receptors under physiological conditions have attracted increasing research interest.10\u201315 However, the methods developed to date have drawbacks including irreversible or imprecise transition between the on/off states and exposure of cells to the soluble counterparts of the ligands during in situ immobilization or cleavage. The limited ability to dynamically regulate immobilized bioactive ligands in engineered systems has hindered the progress of both technological development and fundamental understanding in tissue engineering.
Here we report a novel method of harnessing the molecular recognition of intelligent biomolecules, in combination with polymer engineering, to create dynamic bioactive surfaces on which the accessibility of immobilized ligands to cell surface receptors is reversibly interconverted with high precision under physiological conditions (Figure 1a). We hypothesized that the accessibility of an immobilized bioactive ligand to cells could be dynamically regulated through reversible co-immobilization and removal of poly(ethylene) glycol (PEG) that, when coimmobilized, shields the surface-bound ligand from access by cells.16 We expected that reversible co-immobilization and removal of PEG could be achieved by exploiting the molecular recognition between a pair of complementary leucine zipper domains A and B, which heterodimerize through non-covalent, reversible interactions.17, 18 In the molecular design illustrated in Figure 1a, a bioactive ligand of interest is fused to one terminus of the leucine zipper A and immobilized on a surface through a residue at the other terminus. The modified surface allows co-immobilization of a B-PEG conjugate, which shields the surface-bound bioactive ligand and converts it to a cell-inaccessible state. To convert the ligand back to a cell-accessible state, non-immobilized polypeptide A is added in excess to compete with the immobilized A for binding to B-PEG so that B-PEG can be removed from the surface. This molecular design allows the immobilized ligand to be reversibly interconverted between cell-accessible and cell-inaccessible states under physiological conditions as many times as needed. The bioactive ligand remains immobilized during the dynamic regulation, so cells will not be exposed to the soluble counterpart of the ligand. An additional advantage of this design is that heterodimerization between A and B allows the bioactive ligand and PEG to be co-immobilized uniformly on the molecular level, preventing the formation of ligand islands free of PEG chains. Such islands would likely form when a conventional co-immobilization method is used, and they would compromise the precise switch of the ligand between cell-accessible and cell-inaccessible states.
The polypeptides and their sequences used in this study are shown in Figure 1b. The complementary leucine zipper domains A and B were chosen because they could heterodimerize with an affinity (in the range between 10\u22128 M and 10\u221210 M) higher than that of homo-oligomerization (self-aggregation) of A or B.17, 18 The cell-adhesive RGD peptide was chosen as a model bioactive ligand. A cysteine residue was engineered at the N-terminus of A for surface immobilization. All the polypeptides were genetically engineered and biosynthesized. B-PEG conjugates were prepared by allowing Bcys to react with a large excess of PEG-diacrylate through a Michael-type addition reaction or with a large excess of PEG-maleimide through the thiol-maleimide reaction. After conjugation with PEG, B retained its ability to heterodimerize with A, as revealed from the mobility shift of cysARGD in native gel electrophoresis after cysARGD was incubated with B-PEG (SI, Figure S1).
The ability of the surface-immobilized cysARGD to co-immobilize B-PEG through heterodimerization between A and B and the ability of the co-immobilized PEG to shield the surface-bound RGD from access by cells were examined. First, cysARGD and a control polypeptide cysA were each immobilized on piranha-solution-cleaned gold surfaces through the cysteine residue in the presence of 5 mM tris(2-carboxyethyl)phosphine hydrochloride (TCEP). The surfaces modified with cysARGD supported the adhesion of fibroblasts (NIH 3T3) while those modified with cysA did not (Figure 2a and 2b), suggesting that cell adhesion on cysARGD-functionalized surfaces was regulated through the specific interaction between the RGD peptide and cell surface receptors. Then the cysARGD-functionalized surfaces were incubated with B-PEG conjugates of various PEG lengths (10 kDa, 3.4 kDa, 700 Da, and 258 Da), resulting in further modified surfaces exhibiting different cell adhesion properties depending on the PEG size. When the PEG was 10 kDa, the surfaces did not support cell adhesion (Figure 2c); when the PEG was 3.4 kDa, the surfaces partially supported cell adhesion (Figure 2d); and when the PEG was 700 Da or smaller, the surfaces were as adhesive as the cysARGD-functionalized surfaces without additional modification (Figure 2e, 2f). These results suggested that the immobilized cysARGD allowed co-immobilization of B-PEG through heterodimerization between A and B and the shielding effect provided by the co-immobilized PEG increased with its size.
The reversible switch of the surface-bound RGD between cell-accessible and cell-inaccessible states was performed in the presence of cells under physiological conditions. To demonstrate the accessible-to-inaccessible conversion of the immobilized RGD peptide, fibroblasts were allowed to adhere on a surface as shown in Figure 2a for 3 h. Then B-PEG (PEG: 10 kDa, 300 \u03bcM) was added into the culture medium, followed by incubation under shaking (at a speed at which the liquid just started to move to enhance mass transfer) for 2 h. Cell detachment was observed (Figure 3a). A control performed on a cysC10RGD-functionalized surface (C10 is a hydrophilic random coil17) under the same condition did not result in cell detachment (Figure 3b), suggesting that the cell detachment from the cysARGD-functionalized surface was caused by co-immobilization of B-PEG through heterodimerization between A and B. These results not only suggested that the surface-bound cysARGD allowed co-immobilization of B-PEG in the presence of cells under physiological conditions but also showed that even the ligands that had already been engaged in the interactions with cell surface receptors could be converted to the cell-inaccessible state due to the physical, reversible, and dynamic nature of the interactions between ligands and cell surface receptors.
To demonstrate that the cell-inaccessible RGD shielded by PEG could be converted back to the cell-accessible state in the presence of cells, a cysARGD-functionalized surface was further modified with B-PEG (PEG: 10 kDa); cells were seeded on the resulting non-adhesive surface. Non-immobilized polypeptide A (300 \u03bcM) was added in the cell culture medium, followed by shaking incubation (to enhance mass transfer) for 2 h and static incubation (to allow cell adhesion) for 3 h sequentially. The surface was converted from non-adhesive (Figure 2c) to cell-adhesive (Figure 3c), suggesting that the non-immobilized A competed with the immobilized cysARGD for binding with B-PEG and most B-PEG molecules could be removed from the surface when the amount of non-immobilized A was sufficiently greater than that of immobilized cysARGD. The RGD peptide in immobilized cysARGD was consequently converted from the cell-inaccessible to cell-accessible state. After the medium was changed, the cell-accessible RGD could be reconverted to be cell-inaccessible by addition of B-PEG.
Because surface immobilization of an A-ligand can be achieved through various chemical approaches, such as those enabled by the unique functional groups introduced through non-natural amino acid analogs,19 the ligands are not limited to cysteine-free peptides and the substrates are not limited to gold surfaces. For example, a thiol-containing A-ligand can be immobilized to the surfaces of hydrogels functionalized with maleimide or ene,20, 21 so that temporal control of immobilized ligands can be coupled with regulation of substrate stiffness to further optimize cell microenvironments for desired outcomes. In addition, this method potentially allows both temporal and spatial control of ligands. For example, a step gradient of a ligand can be created via micro/nano-printing, even though creation of a continuous gradient might be difficult. One limitation of the method is that the interconversion is not instant, so it cannot be used for applications such as guidance of rapid cell migration. However, this method will find use in many other applications such as regulation of stem cell differentiation, which is stepwise and often involved with changes in microenvironmental signals on the order of hours or days. Even though shaking incubation is necessary to overcome the mass transfer limitation and allow the interconversion to occur at 1 or 2 h (the experiment described in Figure 3a was also tested at 1 h and the same result was obtained) and exposure of cells to the shear stress associated with the convective flow may introduce some complexity, it is expected that the fluid velocity required for convective mass transfer to dominate over diffusive mass transfer is small. The scaling analysis based on the length scale of cells and the time scale required for the interconversion to occur under static conditions (ca. 10 h) suggests that a velocity on the order of 10\u22126 cm/s is enough to result in a Peclet number (the ratio of convective mass transfer to diffusive mass transfer) of 100.22 The shear stress associated with such small velocity is low.
In summary, the molecular engineering approach reported here represents a platform that can be readily adapted to dynamically and reversibly regulate the accessibility of a variety of immobilized bioactive ligands to cell surface receptors under physiological conditions. The materials having such dynamic bioactive surfaces can be used to temporally control the properties of engineered extracellular microenvironments.
", "answer": "To mimic the dynamic regulation of signaling ligands immobilized on extracellular matrices or on the surfaces of neighboring cells for guidance of cell behavior and fate selection, we have harnessed biomolecular recognition in combination with polymer engineering to create dynamic surfaces on which the accessibility of immobilized ligands to cell surface receptors can be reversibly interconverted under physiological conditions. The cell-adhesive RGD peptide is chosen as a model ligand. RGD is fused to the C-terminus of a leucine zipper domain A and this fusion polypeptide is immobilized on surfaces through a residue at the N-terminus. The immobilized RGD can be converted from a cell-accessible to a cell-inaccessible state by addition of a conjugate of poly(ethylene) glycol (PEG) and another leucine zipper domain B (B-PEG). Heterodimerization between A and B allows co-immobilization of the PEG, which shields RGD from access by cells. The shielded RGD can be converted back to a cell-accessible state by addition of non-immobilized polypeptide A, which competes with the immobilized A for binding to B-PEG and removes B-PEG from the surface. This molecular design offers several advantages: the interconversion is reversible; the ligand remains immobilized during dynamic regulation so that cells are not exposed to the soluble form of the ligand that potentially has detrimental effects; the precision of the on/off states is assured by the molecular-level uniformity of the ligand and PEG co-immobilized through leucine zipper heterodimerization. The method can be readily adapted for dynamic regulation of other immobilized bioactive ligands of interest.", "id": 585} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary stabbing headache is a short duration headache disorder that is characterized by brief paroxysms of sharp head pain often located in the first division of the trigeminal nerve , occurring at an irregular frequency , lacking any accompanying symptoms , and not attributable to any underlying cause .\nstabbing headache has also been reported to occur as a symptom of , or in association with , a variety of underlying secondary disorders , including giant cell arteritis [ 2 , 3 ] , pituitary tumors , meningiomas , ocular pathology , ischemic stroke [ 6 , 7 ] , cavernous hemangioma of the frontal bone , and varicella zoster meningoencephalitis .\nstabbing headache has not been reported to manifest as a direct consequence of a small well - circumscribed acute brain lesion , and its pathophysiology remains elusive .\nherein , a lesional cause of stabbing headache , a small acute thalamic hematoma , is presented .\na 95-year - old right - handed caucasian woman presented to our emergency department with the sudden onset of a constellation of spontaneous neurological symptoms .\nshe first noted repetitive , sharp , 12 s paroxysms of pain in strictly the right frontal and supraorbital region , occurring dozens of times per hour but at irregular and unpredictable frequencies .\nher pain was unaccompanied by photophobia , phonophobia , cranial autonomic symptoms , or any visual changes .\nshe did not identify any triggers and tactile stimulation of any area of the head or face did not provoke the pain .\nthese attacks continued until she finally fell asleep in the hospital 12 h later , and upon awakening 6 h later , did not recur .\nminutes after the head pain onset , she noted mildly slurred speech , which also resolved by the following morning , and upon attempting to ambulate she felt very imbalanced , which persisted for several days .\nher past medical history included hypertension , hyperthyroidism , gastroesophageal reflux , osteoarthritis , and a left intertrochanteric femoral fracture sustained after a fall , which was surgically repaired 4 months previously .\npostoperatively she developed cholangitis from choledocholithiasis , an acute pulmonary embolism , and paroxysmal atrial fibrillation , for which she was treated with intravenous antibiotics and placed on long - term anticoagulation .\nshe had no history of any primary headache disorder , denied ever experiencing any focal neurological symptoms .\nher medications included warfarin , fosinopril , omeprazole , metoprolol , digoxin , and methimazole .\nshe lived with her husband and was a retired school teacher . on review of systems , for several months she had ongoing right upper quadrant pain and occasional nausea that had been attributed to choledocholithiasis .\nshe denied jaw claudication , episodes of visual loss , myalgias , or neck pain .\nher general medical examination revealed a well - appearing woman with normal vital signs , and only mild right upper quadrant tenderness . on neurological examination ,\ndeep tendon reflexes were 1 + in the arms , trace at the knees , and she lacked ankle jerks .\nshe had a white blood cell count of 12,000/l , a total bilirubin of 2.3 mg / dl , a direct bilirubin of 1.2 mg / dl , an alkaline phosphatase of 560 \nu / l , a sgot of 341 u / l , and a sgpt of 292 u / l .\nnoncontrast computed tomography of the head revealed a rounded hyperdense lesion in the left lateral thalamus abutting the posterior limb of the internal capsule , consistent with an acute small hemorrhage , along with multiple subcortical lacunes and white matter ischemic changes ( fig . 1 ) .\nthe hematoma volume was estimated to be 0.12 cm using the abc/2 method .fig . \n1axial noncontrast computed tomography of the brain revealed an acute , rounded hyperdense lesion in the region of the left thalamus and likely abutting the posterior limb of the internal capsule ( white arrow ) , corresponding to a small acute hemorrhage axial noncontrast computed tomography of the brain revealed an acute , rounded hyperdense lesion in the region of the left thalamus and likely abutting the posterior limb of the internal capsule ( white arrow ) , corresponding to a small acute hemorrhage the patient was administered fresh frozen plasma and vitamin k to reverse her coagulopathy and ultimately had an endoscopic retrograde cholangiopancreatography , where numerous gallstones were removed .\nthe patient was ultimately discharged to a short - term rehabilitation facility for her imbalance and deconditioning .\nthe correspondence of the acuity of the clinical syndrome with the radiographic demonstration of an acute hematoma strongly supports its causality , although the lack of magnetic resonance imaging makes the exclusion of other acute lesions slightly less definitive .\na fixed site of stabbing headache may signify an underlying symptomatic cause of the disorder , as was the case with this patient .\nalthough a stabbing pain character of headache is not uncommon in association with acute cerebrovascular disease , the diagnosis of stabbing headache has not been well described in this population . in a large prospective series of over 2,000 patients with acute ischemic stroke where headache details were captured at stroke onset\n, 20% of the patients described their pain character as stabbing , although the diagnosis of stabbing headache was not mentioned .\npareja and colleagues mentioned the onset of stabbing headache in a patient with an ischemic stroke to the parietal lobe , but did not describe its laterality and relationship to the site of the stabbing head pain .\npiovesan and colleagues reported the occurrence of stabbing headache in a delayed fashion after an ischemic stroke in three patients who all likely sustained acute middle cerebral artery territory infarctions .\nregarding hemorrhagic stroke , in a large series of 90 intracranial hemorrhage survivors , six patients experienced stabbing headache de novo after intracranial hemorrhage , only one of whom had no premorbid headache history .\nacute thalamic hematomas in particular can lead to headache over half the time , but similar to other deep structures do not lead to headache nearly as often as hemorrhage in the posterior fossa or lobar structures . in this patient , stabbing headache resulted from an acute parenchymal brain lesion in the thalamus , a location vital to the processing of pain . more specifically , the location of the hematoma may have encompassed the ventral posteromedial nucleus of the thalamus , a relay center for sensory input from the trigeminal system .\nthe association of the pain strictly occurring in the right trigeminal distribution with a lesion in the corresponding left thalamus is intriguing .\nsome authors have proposed the disorder results from spontaneous activation of peripheral nerve branches in the trigeminal or upper cervical distribution [ 14 , 15 ] .\nanother theory is that patients with stabbing headache have segmental and fleeting disinhibition of central pain pathways [ 14 , 15 ] . perhaps in cerebrovascular disease , such disinhibition occurs in an acute fashion in those patients with contralateral pain to the site of infarction or hemorrhage . in stroke patients with ipsilateral stabbing headache\nthis report demonstrates an association of an acute thalamic lesion with stabbing headache occurring in the contralateral trigeminal distribution . particularly in an elderly patient or individual taking anticoagulants ,\na small thalamic hemorrhage should be considered in the differential diagnosis of new - onset stabbing headache , even when fleeting .", "answer": "stabbing headache can be encountered in both primary and secondary forms , but has been infrequently reported among patients with stroke , and is not known to be associated with a small well - circumscribed brain lesion . a 95-year - old woman taking warfarin presented with the sudden onset of stabbing headache strictly in the right frontal and supraorbital regions , along with gait imbalance and dysarthria . \n neuroimaging revealed a small left thalamic hematoma . \n this association of an acute thalamic lesion with stabbing headache in the contralateral trigeminal distribution is discussed , along with a brief review of stabbing headache occurring in cerebrovascular disease .", "id": 586} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbladder cancer ( bca ) is the fifth most common cancer in the united states . in 2012 , it is projected that 73,510 people will be diagnosed with bca and 14,880 will die from the disease .\nmuscle invasive bc ( nmibc ) , about 30% of patients will either initially present or later progress to muscle invasive bladder cancer ( mibc ) .\nradical cystectomy ( rc ) with urinary diversion ( ud ) is the ultimate curative treatment .\ndiagnosis of bca in patients aged < 40 years is rare and is extremely rare in patients < 30 years of age .\nhowever , cases of bca have been previously reported in pediatric and young adult patients [ 4 , 5 ] .\nour aim is to report our experience with a young adult patient with mibc and review the literature for the natural history and outcome .\na 28year old caucasian male patient with 10 pack year smoking history with no family history of bca presented to the emergency department with gross hematuria and left flank pain .\nthe patient underwent computerized tomography ( ct ) of the abdomen and pelvis without contrast due to an elevated creatinine .\nct showed a 6 cm fungating mass at the left posterior wall of the bladder extending to the left ureteral orifice and left hydronephrosis .\nno abnormal laboratory findings were noted except for a serum creatinine of 1.73 mg / dl .\nthe patient was initially managed by left nephrostomy tube placement and subsequent transurethral resection of bladder tumor ( turbt ) . during cystoscopy ,\nmultiple large masses originating from the left side of the trigone extending to the prostatic urethra and the right ureteric orifice were noted ( figure 2 ) .\nno attempt was made to obtain muscle bites secondary to the large volume of disease .\nserum creatinine was 1.6 mg / dl following nephrostomy tube placement . the patient was counseled about the possibility for restaging turbt , rc , and urinary diversion by either ileal neobladder or ileal conduit .\nthe patient then elected to undergo rc and ileal conduit urinary diversion as the patient had elevated serum creatinine and was reluctant to perform cic .\nurothelial carcinoma of the bladder in the first three decades of life is extremely rare .\ninvasive disease and only 1.7% had high grade tumor . since the vast majority of young patients with bca present with non \nmuscle invasive low grade disease , these patients have lower progression and recurrence rates compared to older patients .\nthis further suggested that the nature of bca in the younger population is different compared to elderly patients . on the otherhand , yossepowitch and dalbagni found no difference in grade or stage upon comparing 74 patients < 40 years of age to 75 patients > 65 years of age .\nhowever , when focusing on only bca patients diagnosed in the first two decades of life , it is evident that these patients had a relatively indolent behaving bca . nevertheless , aggressive bca has been reported in children a 31 month old and a 14 year old .\nexposure to polycyclic aromatic hydrocarbons ( pahs ) is responsible for 10% to 15% of cases as a result of bladder carcinogenesis .\ngenetic predisposition to bca has been suggested by reports of multiple case families with bca .\nhowever , it is unclear whether it resulted from a genetic predisposition or common environmental exposure among family members . as in elderly patients ,\nradical cystectomy is the curative intervention for patients with mibc , recurrent high grade superficial bca , and high grade t1 disease .\nprostate and seminal vesicles sparing rc in addition to nerve sparing procedure can be a valuable option for those patients .\npreservation of urinary continence by performing a nerve sparing procedure and orthotopic neobladder urinary diversion is preferred to attain a proper quality of life and body image . in our patient\n, ileal neobladder urinary diversion was not performed due to the patient 's unwillingness to perform cic and the fear of chronic renal insufficiency considering the elevated baseline creatinine , ( 1.73 ) which remained elevated ( 1.6 ) following nephrostomy tube placement .\nthis tendency is more pronounced in patients presenting in the first three decades of life and is likely to decrease with age .\nquality of life and fertility preservation is particularly significant in young patients undergoing radical cystectomy and urinary diversion .\nour case demonstrates a rare example of a high grade t2 transitional cell carcinoma in a 28 year male .", "answer": "the peak incidence of bladder cancer ( bc ) is in the sixth decade of life . \n muscle invasive bladder cancer ( mibc ) in young adults is extremely rare . \n we report a case of mibc in a 28year old smoking male patient . \n the patient presented with hematuria and flank pain for which he underwent a computerized tomography ( ct ) scan of the abdomen and pelvis with and without contrast . \n the ct scan showed a 6 cm mass on the left side of the trigone extending to the left urteric orifice and left hydronephrosis , but no lymphadenopathy was noted . \n the patient then underwent a left nephrostomy tube placement followed by trans \n urethral resection of bladder tumor ( turbt ) . \n the tumor involved both ureteric orifices and extended to the prostatic urethra . \n complete resection was not feasible . \n pathology showed high \n grade t1 urothelial carcinoma . \n ct scan of the chest showed no distant lung metastasis . \n the patient then elected to undergo radical cystectomy with ileal conduit urinary diversion . \n final pathology revealed t2a n0 urothelial carcinoma of the bladder . \n our aim is to present our experience and review the literature for the natural history and oncological and quality of life outcomes of urothelial carcinoma of the bladder in young patients .", "id": 587} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin numerous industrial countries , cerebro - vascular accident ( cva ) has been the third common cause of death after coronary arteries diseases ( cad ) and cancers .\nseveral studies have indicated that higher levels of inflammatory biomarkers such as c - reactive protein ( crp ) and interlukin-6 ( il-6 ) have been associated with worsening ischemic events . \n \ncrp is a systemic inflammatory marker that is produced in a large amounts by hepatocytes in response to il-1 , il-6 and tnf factor .\nrapid induction of crp , its long half - life ( 19 hours ) and lack of alteration during day and night in comparison with other acute phase reactants has introduced crp as an important factor for evaluation in inflammatory and infectious diseases .\nnowadays , crp is a confirmed diagnostic marker for the patients with cva and recent prospective investigations showed that crp is clinically helpful for predicting the risk of the next cardiovascular diseases .\nalthough many studies have been conducted on association of crp and cardiac diseases ; only few studies have evaluated its role in predicting mortality in stroke patients . in addition\n, it can be used as biomarker at early phases in diagnosis of stroke , determining prognostic value of therapeutic programs and secondary prevention strategies . in this study\n, we intended to evaluate association of crp as an inflammatory marker with acute cerebral ischemic attack characteristics , risk factors and to determine a cutoff point of hs - crp in predicting early mortality .\nthis study was conducted on 200 patients with impression of stroke who had been referred to emergency ward of university hospital , imam khomeini hospital , tehran , iran , within may 2009 march 2011 .\npatients who had referred earlier than 24 hours after ischemic stroke were enrolled in the study .\n38 patients with body temperature higher than 37.8 c , hemorrhagic stroke and those with previous inflammatory or malignant diseases were excluded .\nmedical history was taken from the patient or his / her relatives if the patient was unconscious or not able to speak .\npatients were evaluated for age , sex , diabetes , hyperlipidemia , ischemic heart diseases , smoking and past history of stroke or hypertension .\nroutine laboratory tests , brain magnetic resonance imaging ( mri ) , transthoracic echocardiography ( tte ) and carotid doppler ultrasonography were done in all of the patients .\nnational institutes of health stroke scale ( nihss ) was used for assessing stroke severity .\ntype of stroke was determined based on toast ( trial of org 10172 in acute stroke treatment ) classification .\nit is able to demonstrate various types of acute ischemic stroke with different etiology and is consisted of 5 sub - groups : large - vessel atherosclerosis , cardioembolic , small - vessel occlusion or lacunar , undetermined etiology , and non - atherosclerotic determined etiologies .\nanother sample for specific tests was stored in room temperature for 20 minutes until clotting .\nserum was stored in -70 c and sent to heart center hospital of tehran university of medical sciences and hs - crp concentration was determined by turbidimetry method and roche kit ( manufactured in swiss ) with using cobaf apparatus ( model integra400 + ) .\nusa ) using chi - square test and student 's t - test for univariate analysis and mantel hansel analysis for multivariate analysis .\nreceiver operating characteristic ( roc ) curve was drawn for demonstrating cut off point of crp for predicting patients mortality within the first week of admission .\nthey had been referred to emergency ward of imam khomeini hospital within may 2009march 2011 .\nmean age of the patients was 67 12 years with a range of 33 - 95 years .\npatients were classified into 3 age groups : 11 patients were younger than 50 years ( 6.8% ) , 81 cases were 50 - 70 years ( 50% ) and 70 patients were older than 70 years ( 43.2% ) .\nclinical demographic evaluation showed hypertension in 77 ( 47.5% ) patients , diabetes in 50 ( 30.9% ) , hyperlipidemia in 56(35% ) , history of cardiovascular diseases in 46(24.8% ) , history of previous cva in 33(20.4% ) and cigarette smoking in 67(41.4% ) patients .\nmean of nihss score was 9.5 8 ( min 1 and max 30 ) . according to nihss score ,\nour patients were classified to 3 sub - groups : nihss score < 7 ( mild neurologic disorders ) , nihss score 7 - 13 ( moderate neurological disorders ) and nihss score > 13 ( severe neurological disorders ) . according to toast classification criteria , large vessel atherosclerosis was seen in 95 subjects ( 58.6% ) , cardioembolic in 11 ( 6.8% ) and small vessel occlusion in 56 patients ( 35% ) .\nregarding roc curve analysis , appropriate cut - off point for predicting patients short time mortality was determined as 2.15 in this study .\nin addition , nihss > 10 was considered as appropriate score for predicting patients short - term mortality ( fig .\nroc curve of variables for predicting mortality in the patients with stroke association between hs - crp and early mortality in the patients with acute cva was significant .\nmean of crp in died patients was 8.9 7 mg / dl and in survived patients was 2.2 5 mg / dl ( p = 0.0001 ) .\nthe hs - crp amounts showed a significant association with early mortality , diabetes , ihd ( ischemic heart diseases ) , smoking and nihss .\nincidence of early onset mortality based on sub - groups of evaluated demographic variables in the investigated patients with acute ischemic stroke nihss : national institutes of health stroke scale ; rr : relative risk ; crp : c - reactive protein after multivariate analysis and adjusting for sex , age , history of heart disease , nihss score and toast , we found hs - crp as an independent factor in predicting early onset mortality .\nsignificantly increased rate of mortality by 13.3 times was seen in patients by simultaneous crp > 2.15 and nihss > 10 as cut - off points for predicting mortality , so that out of 23 patients possessing these conditions 11(47.8% ) died . in the patients who had simultaneously crp > 2.15 ,\nneurological defect severity was more than 10 and diabetes and mortality rate increased about 19 times ; so that out of 13 patients possessing these conditions , 10(76.90% ) died .\ntherefore , co - existence of these three factors in a patient may strongly increase the risk of mortality .\ndeterminant criteria for mortality risk in the patients with cva and comparing them with each other are summarized in table 2 . \n \ncomparing of multivariate factors with early death in the patients with stroke nihss : national institutes of health stroke scale ; rr : relative risk ; crp : c - reactive protein\nthe results of present study showed that hs - crp in the patients with acute ischemic cva who had died within the first week after manifesting symptoms was significantly higher than survived patients .\nin addition , hs - crp levels more than 2.15 mg / dl were considered as cut - off point for predicting mortality in this study .\nin addition , a large number of previous studies have reported that increasing crp at the first hours after stroke was associated with risk of mortality .\nmontaner et al . introduced crp as a powerful factor for predicting mortality after cva . \n \nischemic damage to brain resulted in disturbance in neuroglia activity especially astrocytes adhered to endothelial .\ntherefore , these cells release cytokines and inflammatory factors that resulted in neuron necrosis and vessels endothelial permeability . at the same time by impaired blood brain barrier ( bbb )\npermeability , neutrophils by exiting through endothelial cells , enters into tissues and increase inflammatory markers concentration . as a consequence ,\nit is considerable that numerous articles recommend application of nihss system for more accuracy in stroke severity . \n cut - off point of > 10 for nihss was shown in present study that in combination with an elevated crp > 2.15 was associated with 13 times increase in mortality .\nsimilarly , studies performed by basic et al . and shenhar et al . showed association of nihss and increase in inflammatory factors .\nneurological defect severity and its association with elevated crp were shown in ischemic cycles so that more ischemia resulted in more neurological defect severity . among 16 dead cases , 14 ( 30.4% )\npatients had history of heart diseases and significant association was seen between hs - crp and mortality in relation to ischemic heart disease .\nin addition , a meta - analysis study indicated that crp is directly associated with ischemic heart diseases , stroke and mortality risk . \n \ntime of hs - crp evaluation was a determining factor in early predicting mortality in this study .\nmaximum of plasma crp concentration has been usually reported within 36 to 48 hours after initiating signs of stroke .\na study by winbeck et al . showed that the most appropriate time for obtaining blood samples was 12 - 24 hours after initiating signs and can predict the risk of cardiac and cerebral vascular events . in the present study ,\nthis study showed that there was a direct association between hs - crp and mortality within the first week after stroke .\ncut - off point of crp was 2.15 mg / dl and measuring hs - crp within the first hours after stroke increase the predicting rate of early mortality risk .\nas up to now , a blood biomarker that can introduce accurate information about cause and outcome after stroke has not been known yet , cut - off point of hs - crp can be used for therapeutic decision making .", "answer": "backgroundhigh sensitive c - reactive protein ( hs - crp ) is a systemic inflammatory marker that is produced in a large amount by hepatocytes in response to interleukin-1 ( il-1 ) , il-6 and tumor necrosis factor after ischemic stroke.methodsmeasurement of hs - crp in the first 24 hours of onset in 162 patients suffering from ischemic stroke was done . \n relation of crp with the risk of early mortality , national institutes of health stroke scale ( nihss ) , stroke subtypes and other factors was determined.resultsregarding to roc curve analysis , appropriate cut - off point for predicting patients short time mortality was equal to 2.15 mg / dl in this study . \n significantly increased rate of mortality by 13.3 times was seen in patients with simultaneous crp > 2.15 mg / dl and nihss > 10.conclusionthe result of this study showed that there is a direct association between hs - crp and mortality within the first week after stroke . \n measuring hs - crp within the first hours after stroke increases the predicting rate of early mortality risk with cut - off point of 2.15 .", "id": 588} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvascular complications after a total knee arthroplasty ( tka ) occur in less than 0.5% of cases.1 it is uncommon , with a reported incidence following tka ranging from 0.03 to 0.17%.27 however , when such a complication does occur , it is potentially limb and life threatening .\npopliteal artery pseudoaneurysm is one of the sequelae of popliteal artery trauma and also can cause arterial thrombosis , arteriovenous fistulae , or arterial severance.26 we report a case of a false aneurysm of the popliteal artery after a tka with unusual presentation , difficult diagnosis and successful management .\nright tka was done using mobile - bearing knee prosthesis ( depuy , warsaw , indiana , usa ) [ figure 1a and b ] .\npostoperative rehabilitation was started on the 1 postoperative day and consisted of static exercises and continuous passive motion .\nfor postoperative analgesia , iv fentanyl patient controlled analgesia ( pca ) dose 1.5 ml / h , along with intravenous paracetamol ( 1 g ) thrice daily was used . on the 3 postoperative day\n, she was disoriented , agitated , and had a fall while trying to get up from bed .\nthe passive range of motion ( rom ) was not affected following fall and there was no increase in swelling or hematoma formation .\ndisorientation continued , and on the 4 postoperative day , she had accidental fall again .\nshe gave a significant history of direct blunt injury to the popliteal fossa with the railing of the bed .\nhemoglobin dropped from 8.4 gm% ( 1 postoperative day ) to 6.7 gm% , and she was given packed blood cells .\n( a ) postoperative anteroposterior ( a ) lateral ( b ) view x - ray of right total knee arthroplasty showing implant in situ on the 6 postoperative day , patient complained of swelling and severe pain in her calf , refusing to move her right lower limb . swelling extended from popliteal fossa up to midcalf region and was nonpulsatile .\nvenous doppler examination of the right lower limb was done , which showed no evidence of dvt . while doing the venous doppler , the radiologist suspected an arterial injury .\nthe arterial doppler showed a pseudoaneurysm of the right popliteal artery , of size 3.9 2.6 cm , with hematoma collection extending into calf [ figure 2a and b ] . computed tomography ( ct ) angiography\nwas done for further evaluation and suggested extensive wall calcification of the abdominal aorta and iliac arteries .\na 3 2.5 cm pseudoaneurysm in relation to the right popliteal artery just above the knee joint was seen [ figure 3a ] .\n( b ) color doppler imaging popliteal artery flow pattern across the pseudoaneurysm ct scan with arrow showing location of pseudoaneurysm ( posterior ) ct angiography of both lower limbs with distal runoffs and good vascularity vascular surgeon opined the need for repair of the rent in the artery causing the aneurysm . a repeat ultrasonographic examination done the next day did not show any increase in the size of the aneurysm .\nconsidering the location of false aneurysm , the vascular surgeon decided to go posterior . on exploration , there were significant clots and the rent was found on the posterior surface of the artery of size 2 2 mm .\nthe rent was not on the anterior aspect , indicating that the injury to the artery was as a result of the impact on the popliteal region due to a fall in the immediate postoperative period and not an intraoperative incident as is seen in most of the reported cases of popliteal pseudoaneurysm following tka .\nafter 12 months , the patient remained asymptomatic without any vascular problems . on followup ,\nshe had well felt distal pulsations without any clinical evidence of pulsatile swelling in popliteal area .\ntrauma to popliteal artery in tka is an intraoperative event . it can present as an acute arterial severance or with arterial thrombosis , pseudoaneurysm , arteriovenous fistula , and occlusion.26 pseudoaneurysm of the popliteal artery is one of the uncommon arterial complications which may present early as a pulsatile mass in the popliteal fossa or remains undetected for a long time.236 it can present as a painful calf swelling as in dvt.5 occasionally , it may present very late.7 the reported mechanisms of injury are due to direct trauma to the vessel , like posterior retractor , oscillating saw or pins used to hold the tibial jig , posterior capsular release.26 the diagnosis of a post tka popliteal artery pseudoaneurysm should be suspected clinically , and diagnostic tools such as doppler ultrasonography and ct angiography should be used to confirm the diagnosis.1516 repeat ultrasonography is also valuable in determining whether the aneurysm is increasing in size .\nsmaller pseudoaneurysms which are associated with small defects in the arterial wall can be treated with ultrasound guided compression repair ( ugcr ) .\nthis procedure involves two sittings , week apart , by applying compression at the neck of pseudoaneurysm .\ncompression is performed with the us transducer itself , a procedure that permits direct and continuous visualization of the vessels .\ntypical protocol includes an initial 10 - 20-min compression of the pseudoaneurysmal neck ; if this is not feasible , the pseudoaneurysm itself is compressed .\nanticoagulation therapy decreases the success rate ; therefore , anticoagulants should be discontinued prior to the procedure if possible . drawbacks of this procedure are long procedure time , discomfort to the patient , recurrence , and rupture of aneurysm .\nhowever , due to the nature of the trauma , only a small proportion of these lesions are amenable to percutaneous therapy which is fairly superficial pseudoaneurysm with less hematoma and commonly used for femoral , axillary , and brachial artery pseudoaneurysms.1416 the established treatment for the remainder is open repair with or without popliteal artery bypass grafting with ligation of the native artery .\nopen repair has its own set of difficulties as it involves operating from a posterior approach and exposing the recently placed prosthesis to infection .\nendovascular treatment involves placement of a covered stent across the defect in the popliteal artery.11316 though no long patient series is available , evidence suggests that endovascular treatment is safe and durable as a treatment modality in the treatment of traumatic popliteal artery pseudoaneurysms and can be performed with an acceptable morbidity rate .\nall reported pseudoaneurysms of popliteal artery or inferior geniculate artery are on anterior aspect and due to intraoperative direct injury to the vessel with varied presentation.27 though popliteal pseudoaneurysm is rare , it can be a devastating complication post tka .\nwe hereby reported an exceptional case where there was trauma to the popliteal fossa due to a fall in the immediate postoperative period probably due to disorientation caused by the use of iv fentanyl and the location of arterial rent was on posterior aspect .\nthe clinical presentation of this condition can be confused with that of a postoperative dvt or hematoma formation in early postoperative period and the surgeon should be aware of this condition .\nthe treatment options include an open surgical repair or other described noninvasive techniques such as percutaneous embolization or endovascular stenting .", "answer": "we report a case of posttraumatic false aneurysm of popliteal artery after a total knee arthroplasty in an 82-year - old woman . \n this case is characterized by the distinct history of trauma to the popliteal fossa in the immediate postoperative period and the location of false aneurysm . in addition , the clinical symptoms were similar to those of deep vein thrombosis . the ultrasonographic examination and computed tomography ( ct ) angiography confirmed the diagnosis on 6th day after the surgery . \n ultrasonographic examination 1 day later revealed no increase in the size of false aneurysm . \n she was treated with open surgical repair . \n presenting the difficulty in the diagnosis , unusual location , etiology , and its management is the intention of this case report .", "id": 589} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncarbapenem resistant gram - negative bacteria ( gnb ) such as enterobacteriaceae ( cre ) ( including escherichia coli [ crec ] and klebsiella pneumoniae [ crkp ] ) , pseudomonas aeruginosa ( crpa ) and acinetobacter baumanni ( crab ) are important emerging causes of nosocomial blood stream infections and carry significant mortality .\n urgent threat by the us centers for disease control and prevention ( cdc ) , while the antimicrobial availability task force formed by the infectious diseases society of america had identified crpa and crab of particular importance , because of growing antimicrobial resistance among these isolates and shrinking therapeutic options .\nindian single center studies overall report a prevalence of carbapenem resistance in up to 12 - 15% of enterobacteriaceae and 40 - 60% in a. baumanii and p. aeruginosa .\nhowever , there is little data from india about the clinical profile and treatment outcome of infections caused by these organisms .\nthis was a retrospective study performed at a 600 bed tertiary care facility in chennai , india between may 2011 and may 2012 .\nwe identified all blood culture results that had yielded a growth of carbapenem - resistant gnb during the study period .\nblood cultures were performed using bact / alert ( biomerieux ) culture system , and species ' identification was carried out with vitek - gni card ( biomerieux ) .\nantibiotic susceptibility was performed using disc diffusion interpretive criteria as per revised clinical and laboratory standards institute performance standards .\ngram - negative bacteremia was defined as the isolation of gram - negative bacilli in blood culture specimen in at least two bottles of two different culture sets with clinical features compatible with systemic inflammatory response syndrome .\nclinical parameters analyzed included severity of illness as calculated by acute physiology and chronic health evaluation ( apache ) ii score on the day of bacteremia onset , presumed source of infection and presence of arterial and venous central catheters or hemodialysis catheters .\nthe source of bacteremia was defined on the basis clinical and microbiologic evaluation using infections criteria proposed by cdc .\npresence of risk factors such diabetes , recent surgery , organ transplant and immunosuppression were recorded .\nprior antibiotic usage , dose of colistin and requirement for renal replacement therapy ( rrt ) after treatment with colistin commenced were also noted .\nthe records of 50 patients with bacteremia caused by crec , crkp , crab , crpa were identified and analyzed .\nthe mean age of patients was 52.3 years and 32 ( 64% ) were male .\nthe most common co - morbid condition was diabetes mellitus ( 30% ) , followed by chronic kidney disease ( 22% ) .\nthe total mean duration of hospitalization was 24.68 days with a mean of 11.76 days of intensive care unit ( icu ) care . the mean time to onset of bacteremia was 6.4 days after admission .\nof the 50 patients , 96% had already received antibiotics , including beta - lactam / beta - lactamase inhibitors ( 32% ) and carbapenems ( 40% ) [ table 1 ] .\nthe mean ( standard deviation [ sd ] ) apache ii score at the onset of bacteremia was 19.64 3.8 .\nthirty - eight percent ( n = 19 ) patients had septic shock complicating bacteremia .\nfourteen episodes ( 28% ) of bacteremia were attributed to ventilator - associated pneumonia ( vap ) , 12 episodes ( 24% ) to the central line related bloodstream infections ( clabsi ) , 10 episodes ( 20% ) were due to intra - abdominal infections ( iai ) and 9 episodes ( 18% ) to urinary tract infections .\nthe most common causative organism in our study was crkp ( 44% ) followed by crec ( 26% ) , while crab and crpa were isolated in 20% and 10% patients respectively [ table 2 ] .\nobserved outcome of patients all patients received a loading dose of colistin with a mean of 5.14 million units intravenously followed by a mean 5.18 million units total daily dose .\nmean creatinine clearance ( calculated estimated glomerular filtration rate [ egfr ] ) at the initiation of colistin was 52.48 ml / min .\nsix patients ( 12% ) required rrt after initiation of colistin for worsening renal functions ; all recovered to normal renal function .\nthe overall survival at 30 days was 40% in our study with lowest survival rates for clabsi ( 33.3% ) , with survival rates for vap , iai and urosepsis patients of 35.7% , 40% and 44.4% respectively .\noverall 30 days survival for crab and crkp bacteraemia were lowest ( 30% and 31.8% respectively ) , while survival rates for crpa and crec bacteraemia were 40% and 61.5% respectively .\nwe also found that patients treated with combination therapy had lower mortality ( 44.8% ) compared with colistin monotherapy ( 66.6% ) although this was statistically not significant ( p = 0.35 ) [ table 3 ] .\ncarbapenem resistance in gram - negative organisms is increasingly encountered in healthcare - associated infections in india .\nbacteremic episodes due to these organisms carry a high mortality as shown by previous studies from other countries . in our study , the most common carbapenem\nresistant gram - negative isolate was crkp ( 44% ) followed by crec ( 26% ) with more than half of all episodes due to pneumonia or clabsi , similar to two previous indian studies presented as abstracts in scientific meetings .\nour patients had a high apache ii score ( 19.64 3.8 sd ) and had a mean icu stay of 11.76 days , with a mean time of onset of bacteremia after admission of 6.4 days .\nthese results are in concordance with previous studies implicating these organisms as causes of healthcare - associated infections .\nseriously ill - patients in icus for prolonged periods often require central lines , dialysis catheters , broad spectrum antibiotics , and mechanical ventilation , which make them susceptible to resistant hospital - acquired infections .\nnotably only 40% of our patients had received carbapenems , but virtually all had antibiotic exposure , suggesting that healthcare exposure and overall prior antibiotic exposure may be more important risk factors for developing carbapenem resistant infections rather than prior receipt of carbapenems .\ncolistin has emerged as the cornerstone of therapy for carbapenem - resistant gnb , but the correct dose and frequency of dosing is a subject of on - going study .\nthe mean colistin loading dose in our study was only 5.14 million units followed by mean total daily dose of 5.18 million units intravenously , even with a mean egfr of 52.48 ml / min at colistin initiation .\nuse of low colistin doses may be because of a perceived concern about nephrotoxicity ; our study period was also prior to evolution of new colistin dosing recommendations . in our study , six patients ( 12% ) required new onset rrt due to worsening renal functions after colistin initiation but this was fully reversible with dosing adjustments , which was reassuring and similar to other studies .\nthe overall 30 days survival rate in our cohort was only 40% , but it was difficult to assess whether this was due to sepsis itself or due to underlying severe illness and multiple co - morbidities .\nmortality in our patients was highest when clabsi or vap was the source of bacteremia and when crab and crkp were the causative organisms .\nbetter survival rates from the west have been reported , but similar results to ours have been observed in two previous indian abstract presentations .\nhigher colistin doses are associated with higher microbiologic clearance and reduced mortality at 7 days although 28 days mortality did not differ .\nit is also possible that relatively low dose our patients received may have contributed to mortality .\nwe also observed that patients treated with two drug combinations had a trend towards a higher survival rate than those treated with colistin monotherapy , as observed in other studies also .\nsmall study numbers in the two groups and the fact that more severely ill patients may receive combination treatment , may have resulted in the absence of a statistically significant difference .\nwe acknowledge significant limitations in our study : its retrospective nature , relatively small sample size and absence of a control group for comparison .\nwe have shown that carbapenem - resistant gram - negative bacteremia is a serious healthcare - associated infection in critically ill - patients in indian icus with co - morbidities and prior antibiotic exposure ; k. pneumoniae is the most common organism at our center .\nthirty days survival rate is only 40% and even lower for clabsi or vap or when due to a. baumanii or k. pneumoniae .\ncolistin is the cornerstone of therapy and may need to be studied at higher doses to optimize the outcome ; nephrotoxicity requiring rrt was seen in 12% of patients only and was reversible in all .\ncombinations of other antibiotics with colistin may result in a lower mortality compared with monothrapy , however this needs needs to be explored through a randomized controlled study", "answer": "background : growing antimicrobial resistance and limited therapeutic options to treat carbapenem - resistant bacteremia prompted us to evaluate the clinical outcomes associated with healthcare - associated bacteremia.methods:this was a retrospective observational study of carbapenem - resistant gram - negative bacteremia performed at a tertiary care facility in chennai , india between may 2011 and may 2012.results:in our study , patients had mean 11.76 days of intensive care unit ( icu ) care and mean time to onset of bacteremia was 6.4 days after admission . \n the commonest organism was klebsiella pneumoniae ( 44% ) . \n patients with combination treatment had lower mortality ( 44.8% ) compared with colistin monotherapy ( 66.6% ) ; ( p = 0.35).conclusion : carbapenem resistant bacteremia is a late onset infection in patients with antibiotic exposure in the icu and carries a 30 days mortality of 60% ; k. pneumoniae is the most common organism at our center . \n two drug combinations appear to carry a lower mortality compared with monotherapy .", "id": 590} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbone marrow is the major hematopoietic organ . bone marrow hematopoietic tissues are highly sensitive to toxins , including radiation and chemotherapeutics , which may induce myelosuppression .\nthe cytoactivities of primitive hematopoietic cells may , therefore , be depressed , and the number of peripheral blood cells may decrease substantially .\nin addition , severe myelosuppression may cause infections , inflammation , and bleeding [ 1 , 2 ] . \nit is generally accepted that maintenance of normal hematopoiesis relies on the stabilization of the hematopoietic microenvironment . as the major component of this microenvironment ,\nhematopoietic cytokines play a key role in the regulation of hematopoiesis , controlling the proliferation , differentiation , and maturation of primitive hematopoietic cells [ 3 , 4 ] .\nil-6 is a kind of cytokine with a wide range of biological activities , produced mainly by t and b lymphocytes , monocytes , fibroblasts , and so forth [ 5 , 6 ] .\nrecent studies showed that il-6 involved not only in the progress of the stress reaction , autoimmune , and neoplastic diseases of the body but also in regulation of the proliferation and differentiation of primitive hematopoietic cells , and it is considered as a permissive factor of primitive hematopoiesis .\nof all the cytokines , il-6 is the first one found to be associated with the pathogenesis of the disease , due to its close relation with a variety of diseases under overexpression . in the present study , a mouse model of aplastic anemia\nwas established by using cyclophosphamide in combination with chloramphenicol and co radiation . after modeling ,\nthe in vitro proliferation of bmsc was tested by mtt assay , and the il-6 secretion levels of bmsc were analyzed .\nthis study gives new insights into the hematopoiesis regulating properties of il-6 in mice with aplastic anemia .\nthe procedures of our experiment are in compliance with the principles of laboratory animal care .\nimdm tissue culture media and il-6 elisa kits were purchased from the jingmei company ( chengdu , china ) .\nthe tunel kit was purchased from the boster company ( wuhan , china ) . the fully automatic blood cell analyzer ( hs-18 )\nwas made in italy ; the inverted phase contrast microscope by the chong qing optical instrument factory ( china ) ; the co2 incubator ( mcd-15a ) in japan ; and the fully - automatic elisa meter by the thermo company ( usa ) .\nhealthy balb / c male mice , weighing 1822 g , aged 68 weeks , were provided by the experimental animal center of chengdu university of traditional chinese medicine .\nanimals were housed in a warm , quiet environment with free access to food and water .\nthe radiation source ( co ) was provided by sichuan academy of agricultural sciences . \nbriefly , the mice were irradiated with 2.0 gy co and then treated with daily intraperitoneal injections of cyclophosphamide at 40 mg / kg / day and chloramphenicol at 50 mg / kg / day for the next three days . on day 7 after modeling ,\n20 l blood was taken from the orbital vein of the mouse and diluted with the manufacturer recommended diluent before analysis with the hs-18 fully automatic blood cell analyzer .\neight mice from each group were sacrificed , and the femurs of each mouse were removed .\nthe bmc suspension was prepared according to zhang 's method , and the number of bmc was counted . on day 7 ,\ntwo mice from each group were randomly chosen , the femurs and spleens were removed , fixed in 4% neutral formalin , decalcified , and desiccated , and embedded in paraffin , and then semithin sections were cut .\nafter hematoxylin - eosin staining , the pathomorphological changes of bone marrow and spleen were observed with a light microscope . on day 7 , bmc smears were prepared , and bmc apoptosis was analyzed by tunel , according to the specifications of the tunel kit .\n5 microscopic fields of each slide were randomly chosen and observed under microscope , and the apoptosis ratio was calculated .\non the 4th , 7th , and 10th days after modeling , bmc suspensions were prepared as described above then adjusted to a concentration of 1 10 cells / ml .\nbmc were cultured in imdm supplemented with 15% fetal calf serum at 37c in 5% co2 and saturated humidity . after 48 h of cultivation , culture supernatants were harvested and stored at 20c for il-6 analysis .\nmtt was added to every well , and the culture medium was put back to the incubator .\n4 h later , the mtt was removed and the cells were washed by pbs twice . 100 l of isopropyl alcohol was added to split the cells . then , the enzyme - linked immunosorbent assay was used at the 570 nm to detect the a value of every well .\nall data were expressed as mean standard deviation ( x-s ) , and the t - test was used to evaluate the difference between groups , with p < 0.05 considered to be statistically significant .\nas measured by the fully automatic blood cell analyzer , the number of peripheral blood cells in the aplastic anemia mouse model was notably decreased ( p < 0.05 ) . besides , the number of bmc was markedly decreased ( p < 0.05 ) .\nthese data indicated that the aplastic anemia model had been successfully established ( figure 1 ) . \nthe morphology of the bone marrow tissue had changed obviously after modeling . in our model ,\nthe amount of hematopoietic tissue , as well as the number of hematogenous cells in bone marrow , was obviously reduced .\nthe number of lymphocytes , fat cells , and other nonhematogenous cells , however , increased markedly .\nthese changes were accompanied by interstitial edema and blood sinus expansion ( figure 2 ) .\nthe spleen atrophied , the splenic corpuscle shrank or disappeared , and its structure was clearly compromised .\nspleen blood sinuses dilated , hematopoietic focus disappeared , and megakaryocytes decreased or were absent ( figure 3 ) . \nthe apoptosis rate of bmc from the aplastic anemia group ( 9.75 2.43% ) was significantly higher than that of normal controls ( 3.63 1.06% ; figure 4 ) ( p < 0.05 ) .\nnuclei of the apoptotic bmc were stained red with fast red while nuclei of nonapoptotic bmc were stained blue with hematoxylin ( figure 5 ) . \n\nfigure 6 showed that at the three time points ( 4th day , 7th day , and 10th day ) , the level of il-6 in cultured supernatants of bmsc from the anemia group was significantly higher than that of the normal group ( p < 0.05 ) .\nbmsc displayed long fusiform shape under invert phase contrast microscope cultured more that 2 days ( figure 7 ) .\nthe a value of model group at the three time points ( 4th day , 7th day , and 10th day ) was significantly lower than that of normal group ( p < 0.05 ) ( figure 8) .\nit has many target cells including macrophages , liver cells , stationary t cells , activated b cells , and plasma cells .\nit can play important roles in the acute phase of the immune response , hematopoietic regulation , and other processes .\nrecent studies also found that il-6 can stimulate the formation of myeloid , erythroid , megakaryocyte , and macrophage cloning , in combination with epo , il-3 , and other hematopoietic cytokines .\nas il-6 has important functions in proliferation , differentiation , and maturation of early hsc , it is considered as a permissive factor of primitive hematopoiesis . \ndefective bone marrow stroma , or microenvironment , has been proposed as one of several mechanisms to account for bone marrow failure .\nthis could involve defects in positive- or negative - acting hemopoietic regulator expression by stroma or alteration of normal stroma - stem cell interactions . as the permissive factor of primitive hematopoiesis ,\nthe role of il-6 in the bone marrow hematopoiesis disorder has been subject of intense attention in recent years .\nso far , the precise mechanism of il-6 in hematopoiesis regulation still remains largely unclear . in the present study , a mouse model of aplastic anemia\nwas established by using cyclophosphamide in combination with chloramphenicol and co radiation . after modeling ,\nthe peripheral blood cells and bmc were significantly reduced and the apoptosis of bmc was obviously increased . decreased hematogenous cells and increased fat cells in the bone marrow of the mouse model were easily observable with a microscope .\nfurthermore , the spleen shrank , the splenic sinus was enlarged , and the hemopoietic focus were evidently reduced .\nthese results demonstrated that the bone marrow hematopoietic function was severely injured , and the mice model was successfully constructed . to investigate the level of il-6 secreted by bone marrow stromal cells from the mouse model of aplastic anemia , in the present study , in vitro cultivation of bone marrow stromal cells was employed , and the il-6 level was measured with elisa .\nthe result showed that at the three time points ( 4th day , 7th day , and 10th day ) , the level of il-6 in cultured supernatants of bmsc from the anemia group was significantly higher than that of the normal group , which indicated that the il-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs .\nas a cytokine with a wide range of biological activities , il-6 has very complex functions .\nit is a key component of the inflammatory mediator network , with an important role in the inflammatory response . as an anti - inflammatory cytokine\nhowever , il-6 is also a proinflammatory factor and , when overexpressed , can lead to a variety of diseases .\nsignificantly elevated il-6 levels were detected in the serum of rheumatoid arthritis , diabetes , acute pancreatitis , hiv , and cancer patients [ 1316 ] . \nherodin et al . reported that in radiation - induced bone marrow depressed baboons , a substantial precocious and transient il-6 blood release was detected within hours after irradiation .\nthe origin of the precocious transient il-6 peak observed just after irradiation was not clear .\nit was supposed that the increase of il-6 may be caused by a more precocious il-1 and/or tnf release . in a clinical experiment ,\nfu et al . found that the pretreatment level of il-6 in serum and bone marrow of 37 aplastic anemia patients were slightly higher than that of normal control , but there was no significant difference between the aplastic anemia group and the normal control group .\nsupposed that the change of il-6 level in aplastic anemia patients may be due to an association with inflammatory response , and il-6 may have an effect of immunoregulation and mediate induction in the destruction pathology of bone marrow cells , but the concrete mechanism still needs to be elucidated . in our study , we noticed that in the anemia group , with the increase of il-6 level , the proliferation of the bmsc was obviously impeded .\nthis result indicated that high level of il-6 might be harmful to the proliferation of bone marrow stromal cells and might interfere with the stability of the bone marrow hematopoietic microenvironment . as the main component of the bone marrow hematopoietic microenvironment , bmsc adhere to hematopoietic stem cells , support and regulate the internal environment for the settling , differentiation , proliferation , and maturation of the primitive hematopoietic cells , and secrete a variety of cytokines to regulate hematopoiesis ; therefore , defects of the bone marrow stromal cells can cause hematopoietic disorders of the bone marrow [ 19 , 20 ] .\nthe results of our study suggested that the il-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs and that the abnormal level of il-6 might probably interfere with the stability of the bone marrow hematopoietic microenvironment .\ncurrently , the role of il-6 in the regulation of hematopoiesis process and the specific mechanism remain unclear , so further investigations are needed .", "answer": "parasecretion of the hematopoietic cytokines is considered as one of the mechanisms account for bone marrow hematopoiesis disorder . in this study , the level of il-6 secreted by bone marrow stromal cells from a mouse model of aplastic anemia was analyzed . \n the aplastic anemia mouse model was established with cyclophosphamide in combination with chloramphenicol and 60co radiation . \n the impairment of bone marrow hematopoiesis induced by irradiation and chemotherapeutic drugs was subsequently characterized by peripheral blood cell count , pathomorphological changes , and apoptosis rate . \n furthermore , the in vitro proliferation of bone marrow stromal cells ( bmsc ) and the il-6 secretion levels of bmsc were analyzed . in our model of aplastic anemia , \n the number of peripheral blood cells and bone marrow cells ( bmc ) were notably decreased , and the apoptosis rate of bmc increased . \n furthermore , the proliferation of bmsc was obviously impeded while the il-6 secretion levels of bmsc significantly increased . \n the findings of our study suggested that the il-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs and that the abnormal level of il-6 might probably interfere with the stability of the bone marrow hematopoietic microenvironment .", "id": 591} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is predicted that by 2025 , the prevalence of hypertension ( htn ) will increase by 60% to a total of 1.56 billion worldwide suggesting that htn remains a major public health problem .\nhtn in sub - saharan africa ( ssa ) has also been on the rise with reports indicating higher values in urban settings compared to rural settings [ 24 ] .\nthe prevalence of htn in ssa ranges between 14.5% in rural eritrea , 32.9% in semiurban ghana , and 40.1% in urban south africa .\nlikewise , adequate blood pressure ( bp ) control has been on the decline , ranging between 1.7% in rural ghana , 4% in urban slum dwellers in nigeria , and 21.5% in urban kenya . in cameroon\n, the prevalence of htn spans from 5.7% in rural settings through 21.9% in semiurban to 47.5% in urban milieu , with a national average survey of 31.0% . despite the relatively better bp control in urban over rural settings , levels of adequate bp control as low as 2% to 27.5% ( in men ) and 38.7% ( in women ) \neven though much has been done so far to reduce the incidence of hypertension in urban areas , this has not been the same in rural areas , with public health policies aimed at controlling hypertension mainly directed towards the large cities .\nmost of the studies done so far in these urban areas can not therefore give a true estimate of the extent to which the rural population is affected by this major cardiovascular disease risk factor .\nan analysis of hypertension and its risk factors in rural cameroon will therefore help guide health policy decisions and provide baseline data for future studies aimed at addressing this problem .\nwe therefore had the following as objectives : determining the prevalence of hypertension in the adult population in the moliwe health area in rural cameroon ; identifying the risk factors associated with htn in this rural setting ; determining the extent of bp control in known hypertensive patients in this locality .\na community - based cross - sectional descriptive and analytical study was conducted over a 6-month period ( june 20 to december 28 , 2013 ) in the moliwe health area ( mha ) .\nthis principally rural health area is found in the limbe health district of the south west region of cameroon .\na multistage sampling method was used to select participants from the 5 villages / settlements of the health area : bonadikombo , wotutu , ewongo , moliwe , and tomatal .\nthe sample selected was self - weighted through the probability proportional to size method used . the data of 2005 cameroon census was used as a guide to the sampling frame with households considered as the primary sampling units . using a random start\n, a systematic sample of households was then selected from a list of the approximate cumulative number of households of all the villages .\nthis gave an estimate of the number of households to be selected from each village .\nas the secondary sampling units , two participants were then recruited from each selected household by simple random sampling from a list of eligible households occupants produced by the respective household heads .\nthree hundred and twenty - nine participants were thus recruited from bonadikombo , 113 from wotutu , 112 from moliwe , 96 from ewongo , and 83 from tomatal .\na combined estimate of the prevalence of htn in rural rwanda , tanzania , and malawi of 22% was used .\nwe recruited 733 participants by systematic and simple random sampling methods . at each selected household ,\na questionnaire was administered to each recruited participant to collect information on age , sex , level of education , marital status , status of htn , treatment of htn , smoking , quantity of alcohol intake , physical activity , diabetes status , and family history of htn .\nblood pressure measurements were also done at the home of the participants by a casually dressed clinician not in white coat .\ntwo measurements ( in mmhg ) were taken on the right arm using an automated electronic bp machine ( omron m3 hem-7200-e omron matsusaka co. ltd . , kyoto , japan ) through the standard procedure ( jnc 7 recommendations ) . heights in meters ( m ) and weights in kilograms ( kg )\nwere measured using standard procedures and were used to determine the body mass index ( bmi ) as follows : bmi = weight ( kg)/[height ( m ) height ( m ) ] . who steps surveillance manual\nthe data was entered into epi info statistical software , version 7.0 ( cdc / who , atlanta , usa ) .\nfrequencies and means were obtained for appropriate variables ; chi - square and fischer 's exact tests were used as appropriate to test for associations between binary and categorical variables .\na logistic regression model was built to assess the effect of factors found to be significantly associated with hypertension while controlling for potential confounders .\nan ethical clearance was obtained from the institutional review board of the faculty of health sciences , university of buea .\nadministrative approvals were obtained from the regional delegate of public health as well as from the local chiefs , quarter heads , and camp presidents concerned .\nall patients found to have elevated blood pressure values were advised and referred to the nearest health facility for proper management and follow - up .\nof the 733 participants , 479 ( 39.5% ) were between 20 and 29 years .\nthe male to female ratio was 1 : 1.2 , 35.9% had primary education , and 50.5% were married .\nless than half of the participants ( 47.3% ) had normal bmi and 15% had sedentary life style . a small proportion , ( 2.9% )\nwere known diabetics and 32.7% reported a family history of hypertension ( table 1 ) .\nof the 733 participants recruited , 228 were hypertensive , giving a prevalence of 31.1% ( 95% ci : 27.834.6 ) .\nsixty - six of the 228 hypertensive participants ( 28.9% , 95% ci : 23.235.3 ) knew their status prior to our study .\nof these 66 known hypertensive participants already aware of their status , 14 of them ( 21.2% , 95% ci : 12.133.3 ) had their blood pressures well controlled even though as high as 47 of them ( 71% , 95% ci : 58.781.7 ) were on antihypertensive treatment at that moment ( figure 1 ) .\nage 40 and above , obesity , smoking , alcohol consumption , diabetes , low educational level , and marriage were found to be associated with hypertension ( table 2 ) . after adjusting for all significant factors using logistic regression , only age 40 and above , obesity , low educational level , and marriage\nthere was a progressive increase in the prevalence of htn with age when age below 40 was used as the reference : from 3 folds in the 4059 years , through 8.3 folds in the 6079 years , to 11.6 folds in 80 years age groups .\npeople who were obese had 2.8 times the odds of being hypertensive compared to the nonobese .\nthose who never went to school had 6.7 times the odds of having htn compared to those who had at least high school education ( table 3 ) . since the new recommendations for htn diagnosis and management by jnc 7 in 2003 , no study had been done in rural cameroon . the last published rural study on htn was as far back as 1998 .\nthe 31.1% prevalence of htn observed in the mha is similar to the 31.0% reported in cameroon by kingue et al . and the 32.9% reported by amoah in semiurban ghana but higher than that reported elsewhere [ 3 , 7 , 8 , 12 , 16 , 17 ] .\nhowever , our value was lower than 44.7% reported by williams et al . in rural ghana and 40% reported by chow et al . in rural and urban high , middle , and low income countries .\nour study revealed low hypertension awareness similar to the 32.3% observed in rural ghana by addo et al . and the 32.6% observed by dzudie et al . in urban cameroon .\nhowever , this value is higher than the 11% reported in rural cameroon by mbanya et al . \nthis variation between rural and urban settings could be explained by poor knowledge of the disease , lesser access to health facilities , and poverty , in rural compared to urban communities .\nage was identified to be strongly associated with htn , supporting the findings of other studies [ 9 , 12 , 2123 ] .\nthis is because as people get older , their blood vessels become harder and they are likely to have decreased baroreceptor sensitivity , increased responsiveness to sympathetic nervous system stimuli , altered renal and sodium metabolism , and an altered renin - aldosterone relationship thereby predisposing them to high blood pressure .\nobesity , which is one of the common pathways between diabetes and htn , was also found to be strongly associated with htn in our study , as earlier documented [ 8 , 26 ] .\nlow educational status and being married were strongly linked with htn in our study as reported in previous studies [ 21 , 27 , 28 ] . a poor understanding of the disease and its risk factors and the stress experienced my married couples , respectively ,\ncould put these groups at a higher risk . on the other hand , gender , family history of htn , overweight , and physical inactivity\nsmoking , alcohol consumption , and diabetes mellitus which were associated with htn on bivariate analysis were not significantly associated with hypertension on multivariate analysis by logistic regression .\nthe proportion of known hypertensives who were currently on antihypertensive treatment in our study was similar to the 64.9% reported in ghana but much higher than the 12.5% reported in cameroon\n. the high proportion on antihypertensives may be due to the increase in awareness of htn and the availability and access to antihypertensive medications in cameroon lately compared to 16 years ago . despite this considerable proportion of hypertensive patients being on treatment ,\nreported as low as 3% in rural nigeria and yuvaraj et al . reported 12.5% in rural india\nhowever , higher proportions have been reported ( 33.1% and 63.2% ) among hypertensives in urban and semiurban settings in cameroon , respectively , 56.8% in mexico , and 75.9% in urban india .\nin this context noncompliance to treatment is multifactorial in aetiology with reasons such as inadequate knowledge of htn , intolerance of side effects of medications , and low purchasing power .\nthis study was cross - sectional which means participants declared hypertensive may not necessarily be hypertensive clinically .\nalso , our study was done in a small rural area whose findings may not necessarily apply to all rural cameroonian or sub - saharan african communities . moreover , some known risk factors such as dyslipidaemia , salt intake , and psychosocial and socioeconomic status were not assessed in our study .\nnevertheless , the large sample size , varied sampling method , and execution of standard measurement procedures make the findings of this study robust and accurate .\nalso , the white coat effect which could potentially produce an overestimation of the actual prevalence of hypertension in this setting was minimized since the casually dressed clinician without a white coat did the measurements from the participants ' homes .\nour study revealed that about one out of three adults in the moliwe health area could be hypertensive with only a quarter of them being aware of their status and a fifth of those on treatment having their blood pressure well controlled .\nthis reveals how very much a cardiovascular risk the rural population may be exposed to .\nthere is , therefore , need for massive improvement in awareness through education and repeated patient follow - up in these rural settings alongside the urban ones .\nalso , the importance of further research in other rural communities to assess trends and risk factors of hypertension and the extent of blood pressure control can not be overemphasized .", "answer": "background . despite the increasing trends suggesting that hypertension is a growing public health problem in developing countries , studies on its prevalence , associated risk factors , and extent of blood pressure control have been inequitably done in urban and rural communities in these countries . \n we therefore aimed to determine the prevalence of hypertension and extent of blood pressure control in rural cameroon . \n methods . \n this was a community - based cross - sectional study conducted in rural cameroon ( the moliwe health area ) . \n participants aged 21 years and above were recruited by a probability proportional to size multistage sampling method , using systematic sampling for household selection and random sampling for participant selection . \n blood pressure , weight , and height were measured by standard methods . \n hypertension was defined as bp 140/90 mmhg . \n results . \n the prevalence of hypertension among the 733 participants recruited was 31.1% ( 95% ci : 27.834.6 ) and 71% ( 95% ci : 58.781.7 ) of these hypertensive patients were newly diagnosed . only 21.2% ( 95% ci : 12.133.3 ) of known hypertensives had a well controlled bp . \n age , obesity , low educational status , and being married were associated with htn after adjusting for confounders . \n conclusions . the high prevalence of hypertension and inadequate bp control among known hypertensives in rural cameroon warrants greater sensitization and regular screening to reduce hypertension - related morbidity and mortality .", "id": 592} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncongenital seminal vesicle cysts associated with abnormalities of the upper urinary tract are uncommon.1 they can be asymptomatic and discovered incidentally or can be associated with dysuria , urinary tract infections , and infertility .\ndiagnosis is more frequently made in adult life during the period of the greatest sexual or reproductive activity.1 \n 2 we present a case of a congenital seminal vesicle cyst associated with ipsilateral renal agenesis incidentally discovered on ultrasound at the age of 4 years and its natural evolution until adolescence .\nthe association of congenital seminal vesicle cyst with ipsilateral renal malformations is rare and was first described by zinner in 1914 .\nit is reported in literature as zinner syndrome.3 this condition is considered as the male equivalent of mayer - rokitansky - kustner - hauser ( mrkh ) syndrome described in females.4 \n\na 4-year - old boy with known right renal agenesis discovered on antenatal ultrasound , presented in our radiology department for his annual control .\nthe cyst was anechoic , measured 8 mm , and was not present on previous ultrasounds .\nit was initially considered as an ureterocele or bladder diverticula , however , neither of these diagnosis was confirmed on intravenous urography performed at that time .\nthe cyst remained unchanged on size and aspect during 11 years of follow - up .\nhowever , at the age of 15 years its aspect on the ultrasound had changed : its content was hyperechoic , it had increased in size ( measuring 1.9 cm ) , and protruded in the bladder .\nit was associated to magma of some echogenic , round retrovesical masses , initially considered as lymph nodes ( fig .\n1b , c ) . magnetic resonance imaging ( mri ) of the urinary tract and pelvis was further performed ( coronal , axial , and sagittal t2 spin - echo and axial t1 with fat saturation before and after gadolinium injection images ) .\nit revealed a dilatation of the seminal vesicles , ipsilateral to renal agenesis ( corresponding to the magma of retrovesical round masses seen on ultrasound ) , ending to a relatively small seminal vesicle cyst ( diameter of 2 cm ) that protruded in the bladder ( fig .\n2 a c ) . \n ultrasound ( a ) at the age of 4 years detects a right retrovesical anechoic cyst ( + ) ( b ) at the age of 15 years the cyst has increased in size and it has become hyperechoic ( white arrow ) .\n( c ) it is associated to magma of round retrovesical masses ( black arrow ) . \n\n( b ) t2 spin - echo axial and ( c ) sagittal images of the pelvis show dilatation of the right seminal vesicles ( white arrow ) ending to a seminal vesicle cyst ( * ) that protrudes in the bladder .\nso far , the patient was asymptomatic and had never presented with dysuria , signs of bladder obstruction or urinary tract infection .\nhe had neither any perineal discomfort nor pain , he described normal ejaculation without pain , no hematospermia , and had never experimented any urinary infection or prostatitis and also he was not sexually active . in this particular case , in the absence of symptoms and because of the relatively small size of the cyst a conservative treatment was decided , with an annual clinical and ultrasonographic control , at least until the first symptoms appear .\nthe association of congenital seminal vesicle cyst with ipsilateral renal malformations is rare and there are approximately 200 cases reported in the literature.4 \n this association is explained by the common embryologic origin of both the organs ( kidneys seminal vesicles ) from the mesonephric duct1 and is due to an insult in embryogenesis between the 4th and 13th week of gestation.4 the ureteral bud arises from the dorsal part of the distal mesonephric duct and extends dorsocranially to meet and induce differentiation of the metanephric blastema , from which the kidney will develop .\nthe mesonephric duct will differentiate to epididymis , ejaculatory duct , vas deferens , seminal vesicle , and hemitrigone .\ncomplete failure of the mesonephric duct results to absence of ipsilateral kidney , ureter , hemitrigone , and seminal vesicle .\nanomalous development of the distal mesonephric duct results to atresia of the ejaculatory ducts and abnormal ureteral budding ; the former leads to obstruction and cystic dilatation of the seminal vesicles with development of seminal cysts , the latter leads to renal agenesis or dysplasia.2 \n 5 zinner syndrome could be considered as the male equivalent of mrkh syndrome described in females.4 \n the cysts are present since birth but enlarge and become symptomatic on late adolescence or adult life , usually in the third to fifth decade , at the period of greatest reproductive or sexual activity.1 \n 2 at this moment the accumulation of secretions in the seminal vesicle due to atresia of the ejaculatory ducts and consequently insufficient drainage leads to formation of cysts in the seminal vesicle.2 \n cysts smaller than 5 cm are usually asymptomatic and are discovered incidentally .\nlarger cysts can irritate the bladder and be related to pain , dysuria , frequency , hematuria , urinary tract infection , epididymitis or prostatitis , infertility , hemospermia , bladder outlet , or colonic obstruction.1 \n 2 \n 6 malignant degeneration of the cysts has been also reported.2 \n 4 \n this progressive dilatation of seminal vesicle remains often asymptomatic until the dilatation increases to 4 to 5 cm,4 \n 5 unless the obstruction triggers vas deferens dilatation at younger age,5 which was not the case for our adolescent .\nthis dilatation develops slowly , by accumulation of secretions in the seminal vesicle , for many years after puberty , due to congenital atresia of the ejaculatory ducts and consequently insufficient drainage2 : literature reports a majority of cases becoming symptomatic around the third or fourth decade of life .\ndiagnosis can also be made earlier in front of infertility linked to contralateral distal ejaculatory pathway compression by this cystic seminal vesicle.3 \n in our case , the cyst was first seen at the age of 4 years , mimicking an ureterocele on ultrasound . in adolescence\nit increased in size , but remained small and , for this reason , asymptomatic .\ndiagnosis was made on mri , based on its anatomic connection and to the similar signal intensity with the seminal vesicles .\ndifferential diagnosis includes other pelvic cystic masses such as utricular or mullerian cyst , ureterocele , dilated ureter , abscess or lymph nodes,2 \n 4 and acquired seminal vesicle cysts .\nacquired cysts are usually bilateral and concern older patients with chronic prostatitis or postprostate surgery .\nultrasound raises the suspicion of this malformation but the final diagnosis is usually made by mri ( or computed tomography , with this last method being irradiating ) . in adults\nmore invasive methods as cystoscopy and vasovesiculography are also used for diagnosis.2 \n there is a medical consensus to propose conservative follow - up for asymptomatic or minimally symptomatic cysts.1 \n 4 \n 7 treatment is considered only for symptomatic patients and is surgical .\ndifferent surgical options exist , from the less invasive transrectal or transperineal aspiration of the cyst which gives a transitory relief of the symptoms,1 to more aggressive technics .\ntransurethral unroofing of the cyst by transurethral resection of the ejaculatory duct provides improvement of the quality of semen and improves the paternity rate,3 but this procedure can create injury to rectum , bladder neck , and external sphincter , and induce consequent retrograde ejaculation , and epididymitis . radical treatment , vesiculectomy with resection of ureteral or renal remnants if present , offers the better outcome .\nit was traditionally performed by open exploration but is now well described laparoscopically , with low morbidity and good results in term of symptoms\nrelief and semen parameters.1 \n 4 \n 7 \n 8 \n 9 \n 10 \n 11 few children with surgical indication benefited from this approach.12 \n 13 \n concerning fertility , for patients presenting with difficulty to procreate , with low volume of semen and poor quality of spermogram , treatment shows semen quality improvement , and paternity obtained without other medical help.3 \n 4 assisted reproductive procedures should be kept for patients with infertility persisting after successful surgical procedure.4 \n our case is original as it shows the natural history and evolution of this malformation , from childhood to adolescence .\ncases reported in literature concern , in their high majority the adult population ( or late adolescence ) and these cysts are rarely detected at a younger age .\ncongenital seminal vesicle cysts in patients with ipsilateral renal agenesis are rare but this association is known and should be considered in the differential diagnosis of cystic pelvic masses in males with renal agenesis or dysplasia .\nultrasound is useful for diagnosis but mri provides a more detailed analysis and accurate diagnosis .\ncongenital seminal vesicle cysts in patients with ipsilateral renal agenesis are rare but this association is well known .\npediatric surgeons should be aware and consider this entity in the differential diagnosis of cystic pelvic masses in males with renal agenesis or dysplasia .\nultrasound is useful for diagnosis but magnetic resonance imaging provides a more detailed analysis and accurate diagnosis .", "answer": "zinner syndrome , the association of congenital seminal vesicle cyst and ipsilateral renal agenesis , is more often reported in adults or older adolescents . \n we present a case of a boy , followed up in our hospital since birth for right renal agenesis who at the age of 4 years presented a right paravesical cyst on ultrasound . \n the cyst was initially considered as an ureterocele . \n the diagnosis of zinner syndrome was made later , at the age of 15 years by ultrasound and magnetic resonance imaging ; at that moment the cyst had increased in size and had changed in aspect . \n this malformation should be considered in the differential diagnosis of a pelvic cyst in male patients with renal agenesis .", "id": 593} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na woman in her 30s with acquired immunodeficiency syndrome ( aids ) diagnosed by the fourth - generation hiv testing , with a cd4 count of 3 ( 1% ) cells / mm , presented with weight loss and cachexia . she was started on lamivudine , zidovudine , and nevirapine and then developed hypersensitivity rash and hepatitis . at that time , she also had pancytopenia ( white blood cells 2,950/l , neutrophils 79% , lymphocytes 13% , hemoglobin 9.6 g / dl , hematocrit 29% , platelets 325,000 10/l ) and intra - abdominal lymphadenopathy .\nshe was treated initially for presumptive disseminated mycobacterial infection with isoniazid , rifampicin , pyrazinamide , ethambutol , and clarithromycin .\nshe improved clinically , and her antiretroviral regimen was restarted after three weeks with lamivudine , tenofovir , and efavirenz .\nlater on , she had gained weight , and laboratory results showed the resolution of pancytopenia and hepatitis .\ntwo months later , the antibiotic regimen was readjusted to ciprofloxacin , clarithromycin , and streptomycin injection ( for one month ) according to the susceptibility , and her clinical improvement was remarkable .\ntwo months after the initiation of antiretroviral therapy ( art ) , she had an hiv viral load of < 40 copies / ml and a cd4 count of 1 ( 2% ) cell / mm ; however , she had recurrent transaminitis .\nshe was given prednisolone 20 mg / day with a tapered dose for five weeks for the treatment of hepatitis possibly due to immune reconstitution inflammatory syndrome .\nfive months after the initiation of art , her cd4 count was 13 ( 3% ) cells / mm , with an hiv viral load of < 40 copies / ml .\nshe developed cytomegalovirus retinitis and received intravitreal ganciclovir injection and oral valganciclovir for six weeks .\nshe then developed abdominal pain , with a palpable large suprapubic mass , for three weeks .\na computed tomography ( ct ) scan of the abdomen showed a large lobulated mass ( 8.5 10 cm ) with the epicenter at the right adnexa and with the invasion of the uterus , right ovary , right lateral wall of the sigmoid colon , appendix , superior wall of the urinary bladder , and right distal ureter , causing right ureter obstruction and a moderate degree of right hydronephrosis .\nmultiple matted lymph nodes were present along the mesenteric root and in the para - aortic , aortocaval , and retrocaval regions .\nfocal circumferential wall thickening of the left side of the jejunum caused moderate intraluminal narrowing , with evidence of small bowel obstruction ( fig .\nshe underwent exploratory laparotomy ; intraoperative findings revealed a large pelvic mass with nodular surface and with dense adhesion to the omentum , the anterolateral wall of the uterus , the bladder , and the sigmoid colon\n. only partial resection of the omentum and a biopsy of the mass at the anterior aspect of the uterus were performed .\nacid - fast and gomori methenamine stains of the tissue specimen were negative ; however , microbial culture was not sent for laboratory analysis .\nher hospital course was complicated by wound infection / dehiscence , with the formation of an enterocutaneous fistula .\nshe suffered from abdominal pain as well as malnutrition due to the nature of the unresectable residual mass and the enterocutaneous fistula .\nshe was discharged home on palliative care , with antimicrobial therapy , and was lost to follow - up . disseminated m. simiae infection presented with pancytopenia , hepatitis , and lymphadenopathy , similar to mycobacterium avium infection in an aids patient.1 effective antimicrobial treatment of m. simiae included rifampicin and ciprofloxacin .\nour patient had an abnormal host immune response to infection , malakoplakia , which occurred after m. simiae infection , a condition that has not been previously described in the literature .\nhowever , we were unable to demonstrate a direct correlation due to the lack of microbiological data from tissue specimens .\nmalakoplakia has a gross appearance of round , oval , or mushroom - shaped yellowish structures.2 histologically , there is a proliferation of histiocytes with abundant granular eosinophilic cytoplasm ( known as von hansemann histiocytes ) that contain the pathognomonic michaelis \ngutmann bodies.2 these bodies are round to oval in shape and are visible as deeply basophilic structures , which are typically described as target - like and are periodic acid \nschiff stain - positive and calcium - positive.2 pathogenesis of malakoplakia is associated with the lysosomal dysfunction of macrophages in the intracellular killing process of ingested organisms and/or a defect in elimination , resulting in the accumulation of partially degraded bacteria within the cytoplasm and phagolysosomes of histiocytes , forming michaelis \ngutmann bodies around the undigested bacteria.2 the most common infectious etiologies described are bacteria , such as escherichia coli , rhodococcus equi , pasteurella multocida , and mycobacterium tuberculosis.211 malakoplakia often occurs in immunocompromised patients , such as those with aids , organ transplant recipients ( mostly solid organ transplants ) , and in one case a patient who had undergone stem cell transplantation.5,1114 malakoplakia affecting a major organ could result in various organ dysfunctions .\none of the most serious adverse events reported was irreversible renal allograft dysfunction due to malakoplakia in a renal transplant recipient with e. coli infection , pyelonephritis , and bacteremia.14 in an allogeneic stem cell transplant recipient , pleural malakoplakia caused by r. equi , presenting with a large tumor mass , required a lobectomy.12 in patients with residual disease , successful results have been reported by treating the underlying infection , reducing immunosuppression , improving the bactericidal activity of monocytes with a cholinergic agonist , such as bethanechol , and administering a multivitamin supplement.4,15,16 this is the first report of malakoplakia occurring after m. simiae infection .", "answer": "malakoplakia in an acquired immunodeficiency syndrome ( aids ) patient with disseminated mycobacterium simiae infection presented with a large pelvic mass that caused organ dysfunction from mimicking a tumor . \n malakoplakia is a rare , chronic granulomatous abnormal host response toward infectious agents , presenting as a tumor - like lesion . \n this is the first report of pelvic malakoplakia after disseminated m. simiae infection in an aids patient .", "id": 594} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe missouri department of health and senior services conducted this investigation in response to the hospital s identification of an increased number of tracheal aspirates that were positive for b. cereus collected from newborns who were on ventilators during march may , 2011 .\nall tracheal aspirate culture results obtained in the neonatal intensive care unit ( nicu ) during january 2010june 2011 were reviewed .\nnicu data was also searched for positive b. cereus culture from other specimens , such as blood , body fluids , or tissues .\ninvestigators thoroughly evaluated respiratory management practices in the unit by direct observation , respiratory records review , and an interview with the respiratory therapist .\nseveral environmental cultures were obtained from the flow sensors of the unit s ventilators over the 1-month period .\nb. cereus isolates were forwarded to the centers for disease control and prevention to be molecularly characterized by using multilocus sequence typing ( mlst ) ( 10 ) .\nthe dna was used as a template in pcrs with the primers described on the bacillus cereus mlst web site ( www.pubmlst.org/bcereus ) for the 7 loci which define the mlst scheme .\nthe sequences for the loci glpf , gmk , ilvd , pta , pur , pyca , and tpi were then assigned allele designations .\na greater number of alleles that match between strains indicates a higher level of relatedness ( 10 ) .\nprevalence of b. cereus positive specimens was compared by using the mann - whitney u test .\nretrospective analysis of tracheal aspirate culture results showed significant increase ( p = 0.039 ) in b. cereus isolation between march and may , 2011 ( figure 1 ) .\nno bacillus spp . were isolated from blood , other body fluids , or tissues during the study period .\nthe chart review of the case - patients comprising the cluster of b. cereus colonization revealed that none received a diagnosis of clinical b. cereus infection .\nall patients were treated with vancomycin or tobramycin , or both , for indications not related to b. cereus in tracheal aspirate .\none case - patient died 108 days later without evidence that b. cereus contributed to the outcome .\nepidemiologic curve of bacillus spp.positive tracheal aspirates from newborns on ventilators , january 2010january 2012 .\ninvestigation of the ventilation procedures in the nicu revealed that most equipment used for respiratory care was disposable , designated for single - patient use .\ntelford , pa , usa ; www.draeger.us/sites/enus_us/pages/hospital/evita-xl.aspx ) was used for mechanical ventilation of infants who were intubated to treat severe respiratory compromise .\nthe draeger evita v500 is a microprocessor controlled ventilator offering both mandatory and spontaneous ventilation modes for adult , pediatric , and neonatal patients .\nheated and humidified gas flows from the ventilator unit , through the inspiratory circuit and neoflow air flow sensor to the patient through an endotracheal tube . upon exhalation , gas flows back through the air flow sensor into the expiratory circuit and returns to the ventilator through the expiratory flow sensor and exhalation valve .\nin addition to the ventilator , reusable respiratory equipment comprised a proximal air flow sensor , expiratory flow sensor , exhalation valve , and circuit temperature probe .\nthe sensor closest to the newborn s mouth was an air flow sensor located inside the disposable ventilation circuit ( figure 2 ) .\nfrom 9 environmental cultures obtained from 9 air flow sensors , 1 was positive for bacillus spp . , and was later confirmed as b. cereus by the state public health laboratory .\nmlst was performed for 8 b. cereus isolates from case - patients and for 1 environmental isolate from the air flow sensor .\none locus for the remaining 5 strains did not yield an amplicon for sequencing after repeated attempts and , thus , could not be assigned a sequence type .\nthe isolates that included sequence type ( st ) 73 and st94 were closely related to each other because they differed by merely 1 locus , gmk .\nthe strains that were not fully typed because of the inability to obtain sequences for locus pta were also closely related to st73 or st94 because the other loci matched .\nthere was 1 match between strains isolated from 1 case - patient and the air flow sensor , which was st73 .\nthe contaminated air flow sensor was then sterilized by using a steam autoclave . a repeat culture of this sensor after sterilization was negative .\nwe found that air flow sensors were routinely disinfected by placing them in a container with 70% alcohol solution for 60 minutes .\nafter discovery of the air flow sensor contaminated with b. cereus , the disinfection policy was changed .\nall air flow sensors were first soaked in enzol enzymatic detergent ( asp , irvine , ca , usa ; www.aspjj.com/us/products/enzol ) solution and then sent for steam autoclave sterilization at 134c ( 273.2f ) .\nafter implementation of new disinfection and sterilization procedures , no new cases of b. cereus tracheal colonization were identified in the nursery . in this cluster ,\ncontaminated proximal air flow sensors were the likely source of tracheal colonization with b. cereus in newborn infants , supported by a genetic match by mlst between a strain isolated from 1 case - patient and the contaminated air flow sensor .\nb. cereus transmission from contaminated respiratory equipment has been reported in other geographic areas . in the netherlands , an outbreak of b. cereus infections in a pediatric intensive care unit caused by contaminated reusable ventilator air flow sensors\nswitching to disposable air flow sensors stopped colonization with b. cereus in that unit . in canada , an outbreak of b. cereus infections among patients in an adult icu was linked to colonized ventilator circuitry ( 8) . in the united kingdom , reusable ventilator circuits were also identified as the cause of a b. cereus outbreak among intubated nicu patients ( 9 ) .\nour investigation underscores the necessity of close monitoring of occurrences of bacillus spp . in tracheal aspirates since clustering of such cases\n, b. cereus isolates were either st73 , st94 , or closely related to those sequence types .\nst73 and st94 are associated with strains previously described as having caused illness in elderly persons .\nstrains with st73 were implicated in cases of septicemia ( 12 ) , and of sepsis and pneumonia ( 13 ) . strains with st 94 were recovered from patients with pneumonia ( 14 ) .\nb. cereus strains harboring b. anthracis plasmids such as pxo1 , have also been associated with severe and fatal respiratory infections ( 15 ) .\nall case - patients in our investigation were considered to be colonized with b. cereus without clinical implications .\nsince all of them received intravenous antimicrobial drugs effective against b. cereus , it is conceivable that the clinical course of those patients could have been different without such treatment .\nshould not be routinely viewed as clinically insignificant and further testing to determine exact strain should be considered under appropriate clinical and epidemiologic circumstances .\nproper disinfection of the entire ventilator circuit as recommended by the equipment manufacturer is crucial in avoiding potentially lethal b. cereus infections .", "answer": "we investigated bacillus cereus positive tracheal aspirates from infants on ventilators in a neonatal intensive care unit . \n multilocus sequence typing determined a genetic match between strains isolated from samples from a case - patient and from the air flow sensor in the ventilator . changing the sterilization method for sensors to steam autoclaving stopped transmission .", "id": 595} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbrachial plexus surgery using the da vinci surgical robot is a new procedure . to evaluate the advantages and the restrictions of the technique , a cadaveric study of supraclavicular and axillary approaches was conducted .\nwe found that the axillary approach was useful and advantageous for lower roots , particularly for thoracic outlet syndrome ( tos ) .\nthis report will focus on the evaluation of axillary robotic approach as the advantages and disadvantages of supraclavicular robotic intervention have been widely discussed in the literature .\na human cadaver was subjected to this experiment in paris university ecole europenne de chirurgie anatomy laboratory and da vinci robot system was used .\nthe left arm was tucked along the side and the right arm was placed in a semiflexed position extending toward the anesthesia location near the head , supported by foam and blankets ( figure 1 ) .\na 6 cm long incision was made at the right axillar line , lateral to the edge of the pectoralis major muscle ( figure 2 ) .\na self - retaining chung retractor was placed into the incision to elevate the pectoralis major muscle flap .\nthe robot was docked as a camera ; right and left robotic arm were adapted in the incision area ( figure 3 ) . a 10 mm 0 downlooking scope , maryland forceps , and a curved scissors\nthe working space was maintained with the self - retaining retractor , without co2 insufflation ( figure 4 ) .\nthe subclavian artery was seen in front of the truncus and was positioned to the posterior of the working space .\nsubclavian artery was dissected from the plexus and truncus of the lower plexus was exposed with blunt dissection .\nthe plexus was exposed thoroughly from t1 to c7 levels . in this surgical setting , the operating surgeon , who has\na wide experience in open brachial surgery of the brachial plexus , reported that lower brachial plexus exposure was easier from the axillary working area and a more wide range of motion was achieved to manipulate the robotic tools compared to the supraclavicular exposure for lower part of the brachial plexus .\nthe development of robotic - assisted minimally invasive techniques began in urology , general surgery , and gynecology because of the generally large working spaces available in the abdomen for these types of surgeries [ 14 ] .\nsince then , other surgeons have sought to use robotic devices in other areas , such as the brachial plexus [ 5 , 6 ] .\nbrachial plexus dysfunction can be the result of shoulder trauma [ 7 , 8 ] .\nit can also occur with tos , which encompasses three separate disorders involving compression of the subclavian artery , subclavian vein , or brachial plexus in the triangular space bordered by the first rib , clavicle , and scalene muscles [ 9 , 10 ] .\ncompression of the vessel - nerve package at the thoracic inlet has been treated with soft - tissue ( scalene muscle ) release and/or bone ( first rib ) resection .\nsurgical approaches to first rib resection may be transthoracic , transaxillary , supraclavicular , infraclavicular , or thoracoscopic [ 9 , 10 ] . however , these approaches are typically associated with incomplete resection of the most medial portion of the first rib and neurovascular complications .\ntheoretically , a minimally invasive transthoracic approach can obviate these problems , enabling complete resection of the offending portion of the first rib without neurovascular complication .\n, respectively , reported successful results of robotic en bloc first rib resection for tos treatment via transthoracic and transaxillary approaches [ 9 , 11 ] .\n's techniques were only bony interventions and as being intrathoracic these need to be lung collapsed and lung complication can be waiting risk .\nalthough liverneaux et al . reported techniques and results of upper brachial plexus injury intervention via robotic surgery with a supraclavicular approach , they described the disadvantages as a narrow working space and difficulty to expose the c7 vertebra [ 1 , 5 , 12 ] . to our knowledge , this report is the first to objectively describe robotic axillar brachial plexus exposure .\nthus , we discuss the theoretical and clinical advantages and disadvantages of the axillary approach in the present report .\nthe development of robot - assisted surgery has revealed new perspectives in peripheral nerve microsurgery . minimally invasive\nrobot - assisted surgery could lead to modification of the classic algorithm for the treatment of traumatic brachial plexus lesions [ 6 , 8 ] . to date , exploration of these lesions has not been attempted less than 3 months after the traumatic event because clinical examination can not provide an accurate diagnosis or reliable prognosis in these first weeks .\nearly intervention may enable initial assessment of the lesion and repair of potentially graftable nerve roots .\nseveral robotics properties are particularly adapted to microsurgery , such as high - resolution three - dimensional ( 3d ) visualization with up to 40 magnification , up to 10-fold magnification of surgical movements , elimination of physiological tremors , and the provision of ergonomic work conditions for otherwise uncomfortable surgery .\nrobotic surgical systems allow high - definition magnified 3d visualization of the operative field , provide significant instrument maneuverability , even within a confined space , and may overcome the shortcomings of conventional approaches [ 2 , 5 ] .\naxillary ( infraclavicular ) brachial plexus intervention via robotic surgery has not been described previously .\naxillary intervention was previously performed as an open procedure to expose the plexus or resect the first rib for the treatment of tos .\nmartinez et al . described first rib resection via robotic surgery but not to address plexus injury without transthoracic exposure , a novel minimally invasive approach to the first rib from inside of the chest .\nin addition , gharagozloo et al . reported first rib resection via transthoracic robotic surgery for paget - schroetter disease .\n's techniques were considered more useful for lower brachial plexus viewing and assessing according to gharagozloo et al .\nthe experience of the whole surgical team with robotic technology is important for the procedure . during learning curve period ,\ntwo staff surgeons are required to participate in all procedures to ensure the safety of the program [ 5 , 9 ] .\nmartinez et al . reported importance of the learning curve , not only for the surgeon but also for the entire surgical team and 180 minutes for the initial 10 cases .\nreported exclusion criteria include a history of previous incision in the same area and obesity , which present difficulties in robotic surgery initiation .\nother drawbacks of this new surgical approach are the increased cost of surgical equipment and longer operating time , especially during the learning curve period .\nhowever , we believe that the avoidance of a classic incision leads to significant patient satisfaction for cosmetic reasons and we believe that demand for this procedure from a select group of patients justifies the exploration of alternative ways to avoid classic brachial plexus exposure .\nthis report presents our initial experience with robot - assisted axillary exposure of the brachial plexus region . in our opinion\nrobotic surgery will be used routinely in the future for brachial plexus surgery and particularly for tos that is caused by bone and/or soft tissue . however , newer dedicated surgical instruments need to be developed and further studies should be conducted to evaluate in vivo application and results of this novel approach .", "answer": "brachial plexus surgery using the da vinci surgical robot is a new procedure . \n although the supraclavicular approach is a well known described and used procedure for robotic surgery , axillary approach was unknown for brachial plexus surgery . \n a cadaveric study was planned to evaluate the robotic axillary approach for brachial plexus surgery . \n our results showed that robotic surgery is a very useful method and should be used routinely for brachial plexus surgery and particularly for thoracic outlet syndrome . \n however , we emphasize that new instruments should be designed and further studies are needed to evaluate in vivo results .", "id": 596} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nqualitative and quantitative disturbances in the function of salivary glands are detrimental to the oral environment , adversely influencing patients quality of life.1 \n , \n 2 three pairs of salivary glands , namely parotid , sublingual and submandibular glands , secrete saliva into the oral cavity through specific ducts .\nsalivary glands are extremely susceptible to radiation injuries with parotid glands being more susceptible than others .\nserous acini are more susceptible to radiation compared to mucous acini.1 \n , \n 2 clinical evaluations have demonstrated that subsequent to a single radiotherapy dose , serous acini are immediately destroyed ; however , mucous acini demonstrate no acute histological changes .\ntherefore , immediately after radiotherapy is initiated , patients saliva becomes thicker . with the continuation of radiotherapy , mucous cells\nare also affected and salivary flow rate decreases , depending on the gland that is in the path of direct radiation rays.2 \n , \n 3 the severity of xerostomia depends on the gland involved , radiation dose and dose rate ( the intervals of radiations ) . \n \n\nthe glands that are partially exposed to radiation demonstrate higher salivation compared to the glands that are completely exposed to radiation .\nradiation exposure on one side may not completely affect glands on the other side ; therefore , it may not result in severe xerostomia .\nhowever , directing rays to the nasopharynx exposes parotid glands to radiation on both sides , leading to severe xerostomia.2 \n , \n 3 \n , \n 4 \n \n xerostomia , the most common complication in patients with nasopharyngeal carcinomas following radiotherapy , makes mastication , deglutition and denture wearing difficult for patients .\nin addition to its constant effect on the patient s daily life , long - term xerostomia predisposes the patient to oral candidiasis .\nsubsequent to radiotherapy , these patients run a higher risk of dental caries , especially root surface caries .\nthis higher risk is attributed to a decrease in saliva quality and quantity , a shift in the oral flora towards cariogenic microorganisms , and changes in diet .\ntherefore , it is critically important that dental practitioners have broad knowledge about potential oral complications following radiotherapy procedures in the head and neck region to be able to render efficacious treatment modalities and minimize or eliminate problems.2 \n , \n 5 \n \n no definitive treatment modalities or preventive measures have been introduced for xerostomia to date . in our community\nno studies have been carried out about xerostomia ; therefore , we decided to evaluate xerostomia in patients under radiotherapy before engaging in an interventional study and comparing various procedures and confounding variables .\nwe decided to use the results of this preliminary study in the following interventional study to determine factors involved in decreasing xerostomia severity .\nsince , according to some studies , xerostomia and other concomitant complications of radiotherapy begin to manifest themselves approximately in the third week of the procedure we decided to compare the third week data with baseline records . \n\nthe study was carried out in the radiotherapy department of tabriz imam khomeini hospital . \n \n\nall of the patients referring to the department of radiotherapy from 22 june 2005 to 21 june 2006 , who had the following inclusion criteria , were included in the study : \n \n nasopharyngeal carcinomas with similar stages , i.e. local and local advanced stages \n \n no history of surgical removal of salivary glands \n \n absence of any signs and symptoms of distant metastasis \n \n no history of saliva - reducing medications , such as anticholinergics and antidepressants \n \n absence of diabetes ( evaluated with fbs test before the study ) \n \n a questionnaire was filled out for each patient .\nthe patients were asked to refrain form eating , drinking , brushing and smoking at least for two hours before sample collection .\nin addition , they were given identical hygienic and food regimens . during the study all removable prostheses were removed so that they could not function as foreign bodies which can act as impeding factors in salivation .\nall the samples were collected in one well - illuminated room while the patients were in a sitting position . \n \n\nthe radiotherapy of these patients was an external procedure , in which the nasopharyax and lymph nodes of the neck received cobalt 60 ( ~6mv ) radiation with two lateral fields , which consisted of an initial dose of 4400 - 4500 cgy in 25 sessions ( fractions ) , comprising 180 - 200 cgy daily . \n \n\nthen , after a two - day interval , spinal cord was removed from the radiation field and the field was tailored .\nbased on the case involved , the patients received a booster dose , which is a procedure called conventional radiotherapy .\n \n \n saliva samples were collected by spitting method three times , i.e. before treatment , 3 weeks after the initiation of treatment and at the end of treatment . \n \n during sample collection\n, the patients evacuated their saliva into a glass every 60 seconds for 2 - 5 minutes and then the volume of the sample was measured with a graduated pipette and recorded in the patients questionnaires . \n \n\none - way anova to test the significance of differences between means , paired sample t - test for the two - by - two comparison of means , independent sample t - test to compare the differences in the mean values between independent groups , and pearson s correlation coefficient to evaluate the relationship between quantitative variables were used .\n\n one - way anova to test the significance of differences between means , paired sample t - test for the two - by - two comparison of means , independent sample t - test to compare the differences in the mean values between independent groups , and pearson s correlation coefficient to evaluate the relationship between quantitative variables were used .\n\n a total of 30 subjects were studied , 63.3% being males and 36.7% females ( 19 males and 11 females ) .\nmean age of the patients was 51.1715.44 ; mean age of females and males were 51.3614.88 and 51.0516.16 , respectively .\nmean values of salivation before radiotherapy in the study population , and in males and females separately , were 1.320.37 ml , 1.340.41 ml , and 1.250.30 ml in 5 minutes , respectively . \n \n\nmean values of salivation in the third week after the initiation of treatment in the study population , in males and females separately were 0.840.35 ml , 0.850.38 ml and 0.800.90 ml in 5 minutes , respectively .\nmeans of salivation at the end of treatment in the study population , in males and females separately were 0.420.31 ml , 0.440.33 ml and 0.380.28 ml in 5 minutes , respectively ( table 1 & 2 ) . \n \n\nsalivation 1 : salivation before radiotherapy : all the subjects \n \n salivation 2 : salivation 3 weeks after radiotherapy : males : females \n \n salivation 3 : salivation at the end of radiotherapy :males compared to females \n \n pearson s correlation coefficient demonstrated the following : there was no statistical relationship between the decrease in salivary flow rate and all patients age ( p = 0.76 , n = 30 , r = -0.057 ) , males age ( p = 0.96 , n = 19 , r = 0.011 ) and females age ( p = 0.539 , n = 11 , r = -0.208 ) . \n\n\n despite great progress in cancer biology and radiotherapy techniques in recent decades , malfunction of salivary glands remains a major and ever - lasting problem subsequent to radiotherapy of head and neck malignancies .\nthe majority of patients experience severe xerostomia , which adversely influences their quality of life .\nthe patients salivary samples were collected by spitting at three intervals : before treatment , 3 weeks after radiotherapy was instituted , and at the end of treatment .\nthe results demonstrated that differences in the means of salivation 3 weeks after the initiation of radiotherapy compared to baseline data , at the end of radiotherapy compared to baseline data , and at the end of treatment compared to 3 weeks after radiotherapy was initiated , were statically significant .\nhowever , there was no relationship between the decreases in the means of salivation and variables such as age and sex .\nthe results of the present study are consistent with the results of studies carried out by jen yee - min et al , 2006 ; nagler , 2002 ; moller et al , 2004.1 \n , \n 3 \n , \n 8 \n \n yee - min attributed the decrease in salivary flow rate to the destruction of cells in serous acini and to the progression of an acute classic inflammatory process , which takes place 24 hours after receiving a 12.5-gy radiation dose . the histologic basis for a decrease in salivary flow rate has not been elucidated to data .\nhowever , recent molecular evaluations have demonstrated that pro - inflammatory cytokines such as tnf- result in a decrease in the release of aquaporin 5 ( a group of membrane proteins responsible for the transportation of water through membranes ) , contributing to a decrease in the production of aqueous solution of saliva .\nyee - min introduced the received radiation does as the most important factor involved in radiotherapy - induced xerostomia . \n \n\nnagler reported that the complications of radiotherapy manifested in the salivary glands in the first weeks after the institution of radiotherapy are transient and secondary to oropharyngael syndrome .\nthe syndrome consists of a transient severe mucositis , resulting in dehydration , malnutrition and inadequate chewing of food due to intense pain .\nnagler introduced cell death through apoptosis as an important factor in early radiation - induced xerostomia ; this cell death was attributed to injuries to membranes as a result of peroxidation of membrane lipids .\nin addition , long - term xerostomia was attributed to the damage to dna , which can be observed during cellular mitosis , and to a decrease in mitotic rate . \n \n\nmoller , consistent with nagler s report , attributed the noticeable decrease in salivation to the death of cells in serous acini through apoptosis in the early stages and to cellular necrosis in the late stage .\nin addition , moller believed the received dose by salivary glands was an important factor in determining the severity of xerostomia , pointing out that more than 2/3 of the baseline salivation is lost during radiotherapy .\nconsidering the results of the above - mentioned studies and the almost identical doses used in those studies and our study ( approximately 60 - 65 gy ) , we believe similar mechanisms were involved in our subjects .\nalthough we have been unable to find a research study , thoroughly evaluating the effects of age and sex on radiation - induced xerostomia , the results of our study in terms of the influence of age and sex on salivary flow rate are consistent with the results of studies carried out by yee - min et al , 2006 ; liu et al , 1990 ; moller et al , 2004 ; shern et al , 1993 ; bretz et al , 2001 ; and fischer , 1990 . however , our results do not coincide with the results of a study carried out by fenoll - palomanes , 2004 , who reported statistically significant relationship between sex and decrease in salivation and also between age and decrease in salivary flow rate . \n \n\npercival attributes the lower rate of salivation in females compared to males , which is statistically significant , to the smaller size of salivary glands in women and hormonal differences .\npostmenopausal females have a lower salivary flow rate but this lower rate can not be attributed to a decrease in estrogen secretion and further comprehensive studies are required . \n \n\nfenoll - palomares believes , in addition to the smaller size of salivary glands in females , higher rate of autoimmune diseases in females compated to males is involved in the lower salivary flow rate in females since autoimmune diseases are important factors involved in xerostomia . \n \n\npercival attributes the disparity between the results of his study with the results of studies carried out by ben - aryeh et al , 1984 , and heft and baun , 1984 , to differences in sample collection methods . \n \n\nben - aryeh and heft and baun did not find any statistically significant differences between males and females .\npercival collected his samples in a 10-minute period ( contrary to 5-minute periods in the present study and other studies ) , which may have resulted in higher volumes of salvation and different results .\nwe , too , attribute lack of significant differences between males and females , in the present study , to differences in the methods employed and recommend further extensive studies to elucidate the role of gender in radiotherapy - induced xerostomia . \n \n\nthere is considerable controversy over the role of age in salivary flow rate and only limited studies have been carried out on the subject .\nresearchers have attributed the differences in results to differences in the methods used , differences in the criteria for case selection , differences in sample collection and finally inclusion of subjects who were taking medications which influence salivation . \n \n\na study by scott in 1977 demonstrated histologic changes in human submandibular salivary glands due to senescence .\nsome researchers believe that unstimulated salivary flow rate decreases with age , which can be attributed to the destruction of the parenchyme of the glands due to senescence . on the contrary\n, some researchers such as fischer ( 1999 ) believe that healthy senile individuals have a salivary flow rate similar to healthy young people and attribute this similarity to the high reserve capacity of salivary glands , especially parotid , which has also been confirmed in the present study . \n\n\n the present study confirms that patients with nasopharyngeal carcinomas will experience severe xerostomia subsequent to radiotherapy , with no statistically significant differences between males and females .", "answer": "background and aims \n salivary glands are extremely susceptible to radiation injuries . \n the aim of this study was to evaluate radiation - induced xerostomia in patients with nasopharyngeal carcinomas , referring to tabriz imam khomeini hospital in 2005 - 2006 . \n \n materials and methods \n thirty patients with nasopharyngeal carcinomas , who received conventional radiotherapy , were included in the present study . \n the patients unstimulated saliva samples were collected at three intervals , i.e. before treatment , 3 weeks after the initiation of treatment and at the end of treatment by spitting , and measured with a graduated pipette . \n \n results \n the differences in the mean values of the patients salivary flow rates at three afore - mentioned intervals were statistically significant ( p<0.001 ) \n . two - by - two comparison of the mean values of salivary flow rates of all the patients and of males and females , carried out separately , demonstrated statistically significant differences ( p<0.0025 ) . \n however , there were no statistically significant differences between males and females before treatment ( p = 0.723 ) , 3 weeks after the initiation of treatment ( p = 0.724 ) and at the end of treatment ( p = 0.595 ) . \n there were no statistically significant relationships between age and a decrease in salivary flow rate in the total sample ( p = 0.76 , r = -0.057 ) , in males ( p = 0.96 , r = 0.011 ) and in females ( p = 0.539 , r = -0.208 ) . \n \n conclusion conventional radiotherapy results in severe xerostomia in 3 weeks in patients with nasopharyngeal carcinomas . \n age and sex do not influence radiotherapy - induced xerostomia .", "id": 597} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhowever , studies have shown that surgery is best done during normal working hours . given the pressures on theatre use\nit is important to be able to assess the retinal detachment and to ascertain the urgency of planning surgical intervention .\none of the most important features is the involvement of the macula and fovea that is macula on or macula off . in cases of macula - off retinal detachments ,\nmacula - on retinal detachments , however , should have their surgery expedited , the main concern being the conversion to a macula - off situation which has a much poorer visual prognosis .\nthe assessment of rhegmatogenous retinal detachments is multifactorial ; in an otherwise normal eye visual acuity is an easy measure of macula involvement with the 6/60 patient being macula off and 6/6 macula on .\nsimilarly the onset of symptoms and the age of the retinal detachment is important , as chronic detachments can be more stable and surgery can be safely delayed .\nalso the extent of detachment and position of the retinal break can also help predict the progression of an acute macula on retinal detachment .\nhowever , in certain situations the macula - on or macula - off question is not easily answered ; visual acuities may be misleading ; examination of the detachment may be difficult due to poor views often due to vitreous hemorrhage and chronicity may be difficult to ascertain in patients with vague histories .\nhigh - speed spectral domain optical coherence tomography ( oct ) offers a noninvasive tool to evaluate retinal microstructural changes in a number of eye pathologies .\nnewer systems using spectral domain calculations have improved data acquisition speeds compared with conventional time - domain oct equipment allowing much greater axial resolution .\ngiven the greater resolution a number of characteristic changes seen in retinal detachment have been observed . in this paper , we discuss two cases where spectral domain oct and an understanding of the histological changes have enabled a clearer diagnosis and planning of treatment .\nour first case is a seventy - five - year - old gentleman who presented with a vague history of blurred vision for six weeks .\nvisual acuity was 6/24 and examination revealed a pseudophakic inferotemporal macula - off retinal detachment .\nthe reduction in visual acuity was thought to be secondary to vitreous haemorrhage as biomicroscopy assessment showed the detachment stopping inferior to the macula ( figure 1 ) . to confirm the macula status ,\ncontrary to the biomicroscopy examination ( figure 1 ) , this revealed a macula - off retinal detachment ( figure 2 ) .\nchanges seen in the oct scan were characteristic of an old retinal detachment with the presence of intraretinal cysts , undulation of outer retinal layers , and the hyper - reflectivity in the photoreceptor layer ( figure 2 ) .\nsecondary to these oct findings , the surgical session was deprioritised and performed five days later .\nthe surgical repair consisted of a three - port pars plana vitrectomy with perfluoropropane tamponade and cryotherapy .\nsubsequent spectralis oct one year following the retinal detachment shows restoration of normal retinal morphology with resolution of the intraretinal cysts , flattening of the retinal layers , and no hyperreflectivity seen ( figure 3 ) .\nour next case was a fifty - year - old myopic female who presented on a friday with a several - month history of floaters and visual distortion described as \nmicrostructural analysis of the macula was performed using a heidelberg spectralis oct scan which confirmed a macula - off retinal detachment ; however , the oct scan revealed that the fovea was bisected by this detachment ( figure 4 ) .\nmoreover , the macula microstructure seen in the oct scan showed no retinal folds or hyperreflectivity present near the fovea .\nindeed , the only morphological retinal detachment changes observed which indicated any chronicity were small intraretinal cysts present peripherally away from the fovea ( figure 4 ) .\ngiven the oct findings , she was treated as a macula - on retinal detachment patient , and surgery was expedited such that an emergency theatre session was organised within 24 hours on a saturday morning .\nthe surgical repair was a three - port pars plana vitrectomy using a sulphur hexaflouride tamponade and cryotherapy .\nafter subsequent cataract surgery , vision had returned to 6/6 with normal oct findings ( scan not shown ) .\nthe morphological changes seen in retinal detachment have previously been evaluated by oct and are becoming clearer with newer systems using spectral domain calculations , which have improved data acquisition speeds to ~40 000 a - scans per second allowing much greater axial resolution to approximately 3.5 m tissue resolution .\nthe transformations seen in retinal detachment include intraretinal cyst formation , intraretinal separation , and undulation of outer retinal layers [ 3 , 4 ] .\nthe disruption of the photoreceptor inner and outer segment junction in macula - off rhegmatogenous retinal detachments is also seen both preoperatively and postoperatively [ 6 , 7 ] .\nmurine models comparing histology and oct confirm these findings and also highlight the hyperreflectivity in the photoreceptor layer which may represent a cellular immune infiltration or misalignment of the photoreceptor layer .\nthese changes were all seen in our first case ( figure 2 ) proving that the retinal detachment had been present for a period of time prior to arrival in our unit and enabling appropriate de - prioritisation within a busy vitreoretinal service . in our second case ,\nin which the fovea was bisected by a retinal detachment , time of onset was in some doubt .\nretinal thickness of the detached retina has been shown to be time dependent initially thickening then thinning with time [ 8 , 9 ] ; however the subfovea thickness was normal when scanned suggesting a recent event along with the absence of any intraretinal cysts , retinal undulations , and hyper reflectivity of the photoreceptor layer ( figure 4 ) .\nonset of retinal detachment is of importance , as experimental retinal detachments in cats have shown that although alterations in the outer nuclear layer occur after 1 hour , progressive loss of photoreceptors continues up to 1330 days , with limited atrophy in cat retinas detached 3 to 7 days .\nhowever , patients that have no tomographic structural changes presumably due to recent foveal involvement have better clinical prognosis .\nthis is most likely secondary to less atrophy and death of the photoreceptors which has histopathologically been shown to be present in prolonged detachment of the retina [ 1014 ] . finally , the height of retinal detachment , which appears to affect the formation of multiple cystic cavities in the detached inner and outer neuronal layers , correlates with poor visual outcome [ 15 , 16 ] .\nall of these features when taken into account suggested a good prognostic outcome for our second patient and hence prompt surgery resulting in an excellent visual recovery ; an outcome that could have been considerably poorer if surgery had been delayed and fovea atrophy had occurred .\nthe morphological changes in retinal detachment seen in oct scans give prognostic factors pertaining to visual outcome and thus help anticipate surgical outcomes .\nthis paper has shown the two scenarios where surgical prioritisation is reversed , that is , from macula on to macula off and secondly , from macula off to macula on . in our first case ,\na chronic detachment was identified by oct and allowed planning within the department for higher priority operations to take place .\nconversely , the lack of subfoveal morphological changes in our second case led to the conclusion that the detachment was recent and prognosis good , thus surgery was expedited .\nwe suggest that if any doubt regarding the status of the macula exists , a routine noninvasive oct should be performed to help clarify the situation prior to surgery .", "answer": "regmatogenous retinal detachments need prompt intervention particularly when macula is on . \n unfortunately this is not always easy to ascertain clinically and the chronicity of the event is often muddled in patient 's histories . \n developments in optical coherence tomography ( oct ) have allowed high - resolution axial scans which have enabled the characterisation of retinal changes in retinal detachments . in this paper \n , we show the changes in retinal morphology observed by spectral domain oct and how this can be used to plan appropriate surgical intervention .", "id": 598} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncastleman 's disease is a lymphoproliferative disorder with benign hyperplastic lymph nodes characterized histologically by ( a ) follicular hyperplasia , and ( b ) capillary proliferation with endothelial hyperplasia ( 1 ) .\nthis disease has been classified histopathologically as hyalinevascular , plasma cell , or a mixed type variant of the two ( 2 , 3 ) .\nthe plasma cell and mixed types are often associated with ' multicentric castleman 's disease ' ( mcd ) , which shows various systemic manifestations , such as fever , anemia , hypergammaglobulinemia , hypoalbuminemia , and an increase in acute phase proteins ( 2 ) .\nmcd is often refractory to conventional therapeutic strategies , such as corticosteroid , cytotoxic agents , and/or radiation ( 4 , 5 ) .\nthe frequency of mcd associated with a lung lesion among the japanese population is high ( ~70% ) ( 6 ) and such progressive lung lesions often lead to death ( 2 , 7 ) .\ninterleukin-6 ( il-6 ) is a pleiotropic cytokine with a wide range of biologic activities , such as hematopoiesis , regulation of immune responses , and inflammatory responses ( 4 ) .\npatients with the plasma cell type castleman 's disease often generate large quantities of il-6 in the germinal centers of hyperplastic lymph nodes ( 8) . '\ntocilizumab ' is a humanized anti - interleukin-6 receptor antibody that neutralizes the pleiotropic actions of il-6 .\nit was approved for use in japan for the treatment of castleman 's disease in 2005 .\nthis report describes a case of mcd with an associated lung lesion , which responded dramatically to tocilizumab in combination with corticosteroid and tacrolimus .\na 43-yr - old female visited a nearby hospital because of abnormal shadows including multiple nodules and reticular shadows on chest radiography found at an annual medical checkup in 2005 .\nthey were unable to obtain a biopsy specimen from one of the nodules in s10 of the left lung because the patient had a strong bleeding tendency .\nshe was referred to this hospital for further examination on june 30 , 2005 . on admission ,\nthe laboratory data were : erythrocyte sedimentation rate , 119 mm/1 hr ; white cell count , 8,900/l ; hemoglobin , 8.4 g / dl ; platelet count , 39.410/l ; serum aspartate aminotransferase , 22 iu / l ; alanine aminotransferase , 22 ; total protein , 9.7 g / dl ; albumin 2.6 ; creatinine , 0.48 ; pt , 13.1 sec ( inr 1.45 ) ; aptt , 39.6 ( control , 10.4 ) ; fibrinogen , 750 mg / dl ; kl-6 , 277 u / ml ( reference range < 500 ) ; c - reactive protein , 11.7 mg / dl ( < 0.3 ) ; serum immunoglobulin ( ig)g , 4,570 ( 870 - 1740 ) ; iga , 491(110 - 400 ) , igm , 706 ( 35 - 220 ) , ch50 , 52.3 u / ml ( 30 - 50 ) , soluble il-2 receptor , 1,400 ; serum il-6 , 6.8 pg / ml ( < 4 ) ; rheumatoid factor ( rf ) , 1,330 iu / ml ( < 20 ) .\nautoantibodies , including antinuclear antibody , anti - ds - dna , anti - sm , anti - rnp , cytoplasmic antineutrophil cytoplasmic antibody ( anca ) , and myeloperoxidase - anca were all negative .\nchest ct scan disclosed a slight enlargement of the mediastinal lymph nodes , centrilobular nodules , thin - walled cysts , the thickening of the bronchovascular bundles , and ground - grass opacities , all of these findings were compatible with those of lymphocytic interstitial pneumonia ( lip ; fig .\ngallium citrate scintigraphy did not reveal any evident accumulation . a lung surgeon and a thoracic physician declined to perform a lung biopsy because of her bleeding tendency ( bleeding time : 6 min 30 sec ) and poor general condition .\na biopsy of an inguinal lymph node was obtained for making a definite diagnosis ( fig .\nshe was diagnosed with mcd and undifferentiated arthritis based on the characteristic pathology of the specimen of the inguinal lymph node , ct findings of the bilateral lung lesions and laboratory data .\nshe was initially administered intravenous corticosteroid ( methylprednisolone , 500 mg / day , 3 consecutive days ) followed by oral corticosteroid ( methylprednisolone , 16 mg / day ) , and , 375 mg / m rituximab every week for 4 weeks .\nthe polyarthralgia instantly disappeared ; however , none of the other clinical and laboratory parameters were fully resolved .\ntherefore the therapeutic regimen was changed to tocilizumab ( 8 mg / kg , every 2 weeks ) , oral corticosteroid ( methylprednisolone , 16 mg / day ) on october 25 , 2005 .\nthe patient requested that the interval between tocilizumab to be increased to more than every two weeks .\nthe dose of corticosteroid in combination with tocilizumab should be kept as low as possible to avoid various side effects , such as osteoporosis , hyperglycemia , and hypertension .\nboth the possible merits and demerits of the drug were explained to the patient and her oral consent was obtained .\nlaboratory findings , including anemia , hypergammaglobulinemia , and an increase in acute phase proteins responded to this regimen ( fig .\nthe enlargement of mediastinal lymph nodes and abnormal shadows were also partially alleviated ( fig .\nthe intervals of the tocilizumab - administration sessions were extended from every 2 weeks to every 3 weeks from january 2006 .\noral corticosteroid was gradually tapered from 16 mg / day finally to 4 mg / day .\nthe treatment of mcd includes various therapeutic strategies such as corticosteroid , chemotherapy , rituximab , or tocilizumab .\nrituximab , an immunoglobulin g1 ( igg1 ) monoclonal antibody to cd20 , has the potential for b - lymphocyte depletion via antibody - dependent cell mediated - cytotoxicity ( adcc ) , complement dependent cytotoxicity ( cdc ) , and apoptosis .\nkaposi 's sarcoma - associated herpes virus ( kshv / hhv8 ) was thought to be associated with the development of castleman 's disease , especially in patients infected with human immunodeficiency virus ( hiv ) and rituximab was reported to be effective in hiv - related castleman 's disease ( 11 ) .\nthe effectiveness of rituximab was limited in the present case because the patient was not infected with hiv . a humanized anti - interleukin-6 receptor antibody , tocilizumab ,\nwas shown to be effective for the treatment of mcd in an open label trial , and has been widely used in japan ( 5 ) .\nthe frequency of mcd associated with a lung lesion is relatively low ( 10 - 20% ) in the united states .\nin contrast , nishimoto et al . reported that 18 of 28 japanese cases ( = 64.3% ) had a lung lesion ( 6 ) .\nthe ct findings of intrathoracic involvement in mcd include bilateral hilar and mediastinal lymphadenopathy , centrilobular nodular opacities , thin - walled cysts , interlobular septal thickening , and ground - glass attenuation ( 9 ) .\nsome reports have noted that the lung lesion in mcd is compatible with lymphocytic interstitial pneumonia ( lip ) ( 5 , 9 ) .\n( 12 ) reported a case of mcd with a lung lesion that responded to tocilizumab .\n( 7 ) described that the administration of tocilizumab for 2 yr had no effect on the lung lesion in an mcd patient .\nil-6 production by the germinal center b cells in the swollen lymph nodes of patients with mcd is remarkable ( 8) , but the roles of t cells are unknown .\nif t cells do participate in the pathogenesis , immunosuppressive drugs for t cells should be useful .\nin fact , mcd , which is classified as a lymphoproliferative disorder , has characteristics of an autoimmune disease , demonstrated by the production of autoantibodies .\nseveral studies have shown that these drugs are active not only against t cells but also against other cells .\nthey suppress the promotion of il-6 in the rheumatoid synovium where t cells are relatively scarce ( 13 ) .\nthey also suppress il-6 production in monocytes , and tnf- production in b cells ( 14 , 15 ) .\npham et al . ( 16 ) reported that inhibition of nf-b and nfat activation in aggressive b - cell lymphomas by calcineurin inhibitors suppressed the cd40 ligand expression in b cells and lymphoma cell survival in an in vitro experiment .\nsome of these actions of tacrolimus , if not all , may be associated with the efficacy of the drug for the treatment of mcd .\n( 17 ) reported that non - cytostatic immunomodulatory therapy including corticosteroid , cyclosporine a and thalidomide treatment was effective for castleman 's disease .\nthe long - time use of tocilizumab and corticosteroid is necessary for the treatment of mcd .\ncorticosteroid has various dose - related side effects , and acquisition of drug resistance possible .\np - glycoprotein ( p - gp ) plays a pivotal role in the latter .\nperipheral lymphocytes in patients with autoimmune diseases could express p - gp on their cell surface .\ncalcineurin inhibitors have an antagonistic activity to p - gp : they may inhibit corticosteroid - resistance in peripheral lymphocytes in vivo ( 18 , 19 ) .\nthe dose of corticosteroid could be tapered in the current case , at least in part , due to the antagonistic activity to p - gp of tacrolimus . in conclusion , this is the first report to describe that tocilizumab , in combination with corticosteroid and tacrolimus , shows a dramatic effectiveness in the treatment of a lung lesion in an mcd patient .", "answer": "this report presents the case of a patient demonstrating multicentric castleman 's disease ( mcd ) with a lung lesion that was successfully treated with an anti - interleukin-6 receptor antibody , tocilizumab in combination with corticosteroid and tacrolimus . \n a 43-yr - old female with abnormal shadows on a chest x - ray was referred to the hospital for further examination . \n she was diagnosed as having mcd based on the characteristic pathology of inguinal lymph node , lung lesions , laboratory data , and undifferentiated arthritis . \n corticosteroid and rituximab therapy did not fully ameliorate the symptoms ; thus , the therapeutic regimen was changed to include tocilizumab , oral corticosteroid and tacrolimus . \n this regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered . \n tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with mcd .", "id": 599} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\norganized by nei dan school , european school of taiji quan and by the tao and science studies centre , under the aegis of the provincia di bologna and the partnership of asi ( alleanza sportiva italiana ) and luni editrice .\ngoodwill of the conference is to act as a starting point to develop a net of experts , doctors and scientists , who will investigate the dynamic interactions between spiritual insight and scientific analysis to come to the creation of a new paradigm of modern science .\nscience , philosophy , medicine and body arts of the ancient east are reunited together to create a new ecological awareness of body and mind .\nmodern science , which paved the way for an outlook of reality considering the universe as a whole , in which all parts and phenomena are connected among them , can be integrated to the ancient eastern wisdom for the control of the mind and to the body arts ( taiji quan , qi gong , yoga ) to develop a new ecological awareness , an awareness based on nature and on the dynamic relation among all living creatures .\nthe conference was divided in two sections : a gathering of experiences , of paths where science meets metaphysics to have a new language born , made of images and movement , and a panel to understand how taiji quan , the arts of movement and meditation , can prolifically meet cognitive sciences and neurosciences .\nspeakers during the tao and science conference were : andrea pezzi ( presenter and tv author ) ; professor edwin l. cooper professor , laboratory of comparative neuroimmunology , department of neurobiology , david geffen school of medicine , university of california los angeles , editor - in - chief , the journal : evidence based complementary and alternative medicine , oxford university press ; professor carlo ventura ( professor of molecular biology at the faculty of medicine , university of bologna ; director of the laboratory of molecular biology and stem cell bioengineering , national institute of biostructures and biosystems by the institute of cardiology of santorsola malpighi hospital in bologna ) ; professor angelo marzollo ( professor of systems theory , faculty of sciences , university of udine ; vice general secretary of the international centre for mechanical sciences ; unesco ex - person in charge for mathematics and now consultant ) ; professor giovanni sambin ( professor of logic mathematics , university of padova ) ; dottor matteo luteriani ( publisher , journalist and master of martial arts ) , dottor massimo mori ( doctor , poet and master of taiji quan ) and eng .\nflavio daniele ( writer and master of taiji quan ) the following guests took part in the conference through their representatives : professor james k. gimzewski ( department of chemistry and biochemistry , university of los angeles \nucla ; director of the pico lab laboratory at ucla ) ; professor aldo stella ( teacher of medical psychology , university of urbino ; teacher of psychology of cognitive processes , university for foreigners of perugia ) ; professor carmelo di stefano ( teacher of teaching didactics of the adapted movement and sports activity , faculty of motor sciences , university of bologna ) .\ncarlo ventura , md , phd : western science has long been entangled with increasing reductionism and the development of field restricted approaches to understand cell biology and the molecular basis of disease .\nit is now becoming increasingly evident that reductionism is a remarkable bias in pursuing some of the major goals of modern biology and medicine .\ncomplex problems , including cell growth and differentiation under normal or malignant conditions ( cancer ) , and the adaptive mechanisms of humans to multiple changes in cell signaling networks now pose the need for holistic approaches both at the molecular biology and medical levels .\nsuch a requirement is even more urgent in spite of the emerging interest in stem cell biology , since taking a glimpse at the mechanisms underlying cell commitment and fate specification may hold promises for a revolutionary field , the so - called regenerative medicine. while moving from reductionism to holistic approaches , the cell is studied as an integrated system , behaving as a neural network with complex and sophisticated logics .\nawareness of these features has progressively led to wide - ranging strategies in the investigation of gene and protein expression .\ntechniques such as the dna microarray and the serial analysis of gene expression ( sage ) are now able to follow the expression of thousands of genes and signaling molecules at a time , attempting to uncover the overall plans that underlie molecular patterning and cellular decisions .\nomics era ( genomics , proteomics ) and will hopefully form the scientific underpinning for moving from basic science to a clinical practice in which physicians will learn how to deal with illness rather than disease ( or even worst , diseased organs ) .\na major sign of these cultural changes is provided by the ongoing development of nanobiotechnologies . in both the philosophical and visual sense ,\n seeing is believing does not apply to nanotechnology , for there is nothing even remotely visible to create proof of existence . on the atomic and molecular scale ,\ndata is recorded by sensing and probing in a very abstract manner , which requires complex and approximate interpretations .\nmore than in any other science , visualization and creation of a narrative becomes necessary to describe what is sensed , not seen .\nwe have growing needs for separating the informational content of life from its material substrate. \ninformation is thought to be the essence of life , as in the dna code ( james k. gimzewski , university of california at los angeles , department of chemistry and biochemistry , director of the pico lab at ucla ) .\nedwin cooper highlighted how different alternative medicines if integrated can be useful to reclaim that holistic view of the diseased person , that an excessive specialization has made modern western medicine lose and he illustrated the work done in this direction by the biomedical journal ecam .\ndisease has always been of enormous concern in human society . from prayers and spells to the birth of medicine as a rational science , man has developed all sorts of medical treatments to combat different illnesses and chronic ailments : according to the chinese proverb : life is worth more than a thousand gold pieces. the first objective in a serious approach to complementary and alternative medicine ( cam ) should be to obtain a broad understanding , with a minimum of detail , of how cam fits into the pattern of biology of the way in which the nervous , endocrine and immune systems coevolved , their function and coordination with other body systems , and their development from the embryo onwards including aging . at the same time , such an outline should provide an adequate background for easy application of cam ideas to the detail of practical cam work in public health , clinical and medical practice , and yet not stray far away from its essence , the very biology that under girds it .\ncam is organismic , considers the whole individual and is inclusive , not reductionist nor exclusive .\nconcerning senescence and age - associated diseases , that accompany longer living populations , substantial attention is now focused on searching for : ( i ) mechanisms of aging and ( ii ) approaches to ameliorate or lessen the effects through the use of therapies , some of which utilize natural products from aquatic and terrestrial plants and animals .\nclearly there are numerous treatments to explore and to understand long past the anecdotal information that has been passed on through centuries .\nthere is evidence for treatment of diseases of an ever - aging society especially in developed countries .\nit is of great interest that these remedies now being refined by ecam approaches derives almost entirely from primitive societies where there are minimal facilities essential for analyses by an evidence - based approach .\nmassimo mori said : [ ] if the scientific research is free , the same is not valid for its technological applications , which have to serve an ecology of culture marked by wisdom , an ecology of the mind , as wrote gregory bateson , in harmony with nature ; nature , where the uncertainty principle of werner heisenberg has scientific and philosophical value ; harmony , comprising the clash and entropy of ilya prigogine as factors of transformation . a holistic view recomposing the divided self of ronald d. laing , giving deepness to the one - dimensional man of herbert marcuse. prof .\nangelo marzollo highlighted the importance of combining the art of to say with the art of to do , i.e. , that the learned man , the intellectual is direct evidence of the ideas carried on by him , that the body does not contradict the mind , that the body - mind unit remains not only a theoretical statement .\ngiovanni sambin said : although the theme is science , i can speak only about my specialization .\ni am fascinated by oriental wisdom , but i know almost nothing about it because of lack of time .\ni am here only because i am trying to learn tai ji quan , with master roberto benetti. mathematics is important in western science .\ngalilei was the first to propose that the laws of nature are written in the language of mathematics .\nthis has been the base for inventions characterizing industrial revolution in xixth century . by using mathematics\nso mathematics is at the base of present - day western technological supremacy . in modern times , debate concerning foundations of mathematics has been most lively at the beginning of xxth century .\none of its outcomes was the invention of programmable computers , which speaks of its importance .\ni am not a believer , but i find constructivism much more convincing than the now dominating theory , which is called classical and is considered by most scientists as an absolute truth .\nto do modern mathematics one needs an abstract notion of concept , or set . in the classical approach , one has classical logic ( by which all propositions are either true or false , any third possibility like abstinence is excluded ) and axiomatic set theory ( all sets are there already , a static universe containing now , and ever , all possible concept - sets ) .\nthe mental scheme looks as something like : classical mathematics is at the base of western science , which is the reason for technological superiority , which makes western people the owners of the world .\nhence it must be that western mathematics , and all what follows from it , is an absolute truth , which can be imposed on others by force .\nneedless to say , this view can be extremely dangerous . here and in all my life ,\nmy aim is to show that a different foundation of mathematics is possible , which has the same applications , but which avoids any form of fundamentalism .\na way of doing mathematics is possible , in which the will of power is replaced by harmony with nature , control is replaced by knowledge , brute external force is replaced by internal energy , the search for the \ni want to emphasize that originally this was not motivated by some ethical or political principles , rather by the search for a better foundation of mathematics .\nmaster flavio daniele emphasized as most advanced research of the last decades of the past century in the field of cognitive sciences and neurosciences led to a new theory , revolutionizing the traditional cartesian concept of mind .\nthis theory , known as the santiago theory of cognition , claims that mind can no longer be regarded as a thing but as a process .\nprocess , which is cognition to which belong perceptions , emotions and actions , the language , the conceptual thought and all the attributes of conscience , which is peculiar to man .\nthis view , perfectly in line with the eastern traditional thought , entails that mind with its cognitive processes goes beyond the rational aspect as it includes the whole process of life .\na further implication of this theory , which will show its vast potential , when it will be absorbed at the general cultural level , is that mind and matter are no longer regarded as separated dimensions , but as complementary aspects of the sole phenomenon of life : the process ( the mind ) and the structure ( the brain ) .\nmind and matter , process and structure are indivisibly connected at all levels of life : from the simplest cell to the most complex organism .\nthis connection is so deep , as most recent studies in the field of cognitive sciences has demonstrated , that we can state , conceptual thought , on the whole , is physically incarnated in the body and in the brain. this goes beyond the simple consideration that to think we need a brain and leads to state that human reason does not transcend body , but it is structurally shaped by our physicality and body experience. a further discovery of cognitive sciences , consequent to it that : ( 1 ) mind is deeply incarnated in the body , and the other that , ( 2 ) thought is mainly unconscious , is that ( 3 ) abstract concepts are to a large extent metaphorical. for the time being , present researchers have not explained in detail the neurophysiological dynamics underlying the formation of abstract concepts ; however , the scientists lakoff and johnson state that the neural and cognitive mechanisms enabling us to sense and move are the same to create also our conceptual structures and our ways of reasoning. this statement that conceptual structures and ways of reasoning come from the same neural and cognitive structures of perception and movement , is extremely important for the practitioners of the arts of movement ( taiji quan , yoga , sacred dances , ritual gestures or mudra ) , as it demonstrates and confirms the creative power of movement , which no longer acts as simple instrument at the service of mind , to play the fundamental role of shaper of the cognitive capabilities ( conceptual thought , speech , conscience ) of the human mind . by paraphrasing maturana and varela\ncognition , the process of knowledge , and it is identical to the process of life self . nevertheless , beyond the dialectics coming from the differences , it is more and more important to reintroduce a principle , acting as basis for the man universally , a principle which is internal and unconventional , an equal able to give the equal to all psycho - biological behaviors of the human being . in italy\nthis kind of research has always taken place , and in recent years has made its way into the experimental evidence of a psychology able to touch this dimension .", "answer": "the conference was organized and supported by : nei dan school ( european school of internal martial arts ) , nib ( laboratory of molecular biology and stem cell bioengineering , national institute of biostructures and biosystems , institute of cardiology , s.orsola-malpighi hospital , bologna ) , wacima ( worldwide association chinese internal martial arts ) , arti doriente ( magazine of eastern culture and traditions ) , nuovo orizzonte ( taiji quan school in florence ) , samurai ( journal on martial arts ) , and pinus ( first national institute for the unification of medical strategies ) . \n nei dan school ( www.taichineidan.com , neidan@libero.it ) was in charge of the organization . \n future meetings of the centro studi tao and science will take place in spring 2007 in firenze and in october 2007 in bologna . for information : \n e - mail : neidan@libero.it ; web site : www.taichineidan.com , www.taoandscience.com", "id": 600} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbilateral ectopic pregnancy is a rare condition and is divided in two subgroups , primary and secondary , based on history of assisted reproductive technology .\na 30 year old primigravid woman with history of infertility and ovulation induction presented to a hospital in kashan in year 2013 .\nshe had vaginal bleeding , abdominal pain and ultrasound findings suggested early pregnancy . due to high titer of -hcg , gestational trophoblastic disease was proposed and d8c was done in referral and admission to gyneco - oncology ward in tehran .\nrepeat sonography suggested ectopic pregnancy in left side and repeat -hcg level showed an increase of 19435 miu / ml .\nbilateral ectopic gestation should be considered as a rare differential diagnosis for ectopic pregnancy . in this study ,\nthe implantation and development of fertilized ovum outside the uterine cavity is observed in approximately 2% of all pregnancies . over 95% of ectopic pregnancies\nbecause of the increase in incidence of sexually transmitted diseases , tubal surgery and more frequent use of ovulation induction and assisted reproductive technologies ( art ) , the incidence of ectopic pregnancies has grown in the last 30 years according to many reports from developed countries .\nectopic pregnancy is still the leading cause of pregnancy - related deaths in developed countries ( 1 ) .\nhowever , bilateral tubal pregnancy is a rare clinical condition which occurs in only 1 per 200,000 pregnancies .\nthis condition is divided in two subgroups , primary and secondary , and because of different physiopathological mechanisms , these two entities should be studied separately .\nhowever , as studies have shown , the cause of bilateral ectopic pregnancy after art is clearly different from spontaneous cases .\nclinical and paraclinical findings of this condition are the same as unilateral ectopic pregnancy so the distinct diagnosis is difficult ( 2 ) . in the present article , a case of bilateral tubal pregnancy\na 30 year old primigravid woman has been hospitalized in kashan in year 2013 due to minimal vaginal bleeding and low abdominal pain .\nshe had been under different treatments including sequential treatment with clomiphene , fsh and hmg in previous cycle .\nher last menstrual period was 8 weeks ago . in admission , vital signs were normal .\nthe first transvaginal ultrasound revealed a suspicious gestational sac without yolk sac in uterus and normal adnexal area was reported .\ndue to high level of -hcg ( 16000 miu / ml ) , without normal viable intrauterine pregnancy , dilatation and curettage had been done to clarify existence of intrauterine pregnancy or its complications or ep .\ndue to high level of -hcg , gestational trophoblastic neoplasm was considered in differential diagnosis besides ectopic pregnancy and it resulted in gyneco - oncology consultation .\nthe rise of -hcg level to 21770 miu / ml , 9 days after operation resulted in referral and admission of patients to gynecology - oncology ward of our center in tehran .\npositive findings in this admission to gynecooncology ward in tehran were low abdominal pain , minimal vaginal bleeding with stable vital signs similar to the ones observed in previous admission . through\nre - checking the -hcg level , titer of 19435 miu / ml was observed .\nthe next ultrasound reported a normal uterus with endometrial thickening up to 11 mm , a heterogeneous mass measuring 49 mm in left adnex , suspicious to ectopic pregnancy and two simple cysts , 69 mm in left ovary and 50 mm in right ovary .\nthere was no free fluid in the pelvic cavity . because of persistently high level of -hcg , surgical intervention was done . atypical findings and diagnosis of gtn besides fp led to choice of laparatomy instead of laparascopy .\nsurgical findings were two bluish , 5 cm in left side and 2 cm in right side , swelling in both ampullary parts of fallopian tubes with minimal bleeding from fimbria .\ntwo simple cysts , about 5 cm in right ovary and 4 cm in left ovary were seen .\nbilateral salpingostomy was performed and some trophoblastic - like tissue was extracted and sent for pathologic evaluation separately .\nthe patient received 50 mg / m intramuscular methotrexate due to bipateral fp and non - radical approach .\nsecondary bilateral ectopic pregnancy is a condition with localization of trophoblastic tissue in both tubes , following a kind of manipulation in physiology such as through the use of art drugs .\nthe classic triad of pain , vaginal bleeding and missed period was present , similar to unilateral ectopic pregnancy . in a study , 19 secondary bilateral tubal pregnancy cases were reviewed in an attempt to examine the symptoms and signs .\ndiagnosis in this group was done due to discrepancy between sonography and -hcg level . in 6 out of 19 ( 31.6% ) cases ,\ndue to involvement of both fallopian tubes , probability of rupture is higher in comparison to unilateral ectopic gestation ( 2 ) . in the case of the present study , as a secondary bilateral ectopic gestation , high level of -hcg without intrauterine pregnancy suggested ectopic gestation and atypical high titer of hcg resulted in referral to a tertiary gyneco - oncology ward . in review of studies , mean gestational age at the time of diagnosis was about 6.7 weeks ( 5 - 9 weeks ) after the last menstruation ( 2 ) .\nsonographic findings and -hcg level , usually , do n't lead to a correct diagnosis of bilateral ectopic pregnancy . due to ample amount of -hcg during normal gestation , its level is not diagnostic ( 13 ) . in a review of hcg level in 16 cases of secondary bilateral tubal pregnancy ,\nmean level of -hcg was 20878 miu / ml with a wide range of 27 - 226768 miu / ml .\nthree cases out of 16 revealed -hcg titers of 13296 , 62520 and 226768 miu / ml ( 2 , 47 ) . in unilateral ectopic pregnancy , there is lower level of -hcg .\nin contrast to normal pregnancy with predictable range of -hcg in each week of gestation , in ectopic pregnancy it is more variable ( 2 , 3 ) . in our case ,\nempty uterus coexisting with high level of -hcg suggested gestational trophoblastic disease ( gtn ) and ectopic pregnancy was less probable due to high atypical titer 21770 miu / ml hcg . high level of -hcg titer in bilateral ectopic gestation , such as above 10,000 in 3 case reports and our case and even 226768 miu / ml in a case report , proposed gtn as a reasonable differential diagnosis .\nhowever , pre - operative diagnosis of secondary bilateral ectopic pregnancy was made just in 10% of patients ( 2 ) . in our case ,\nbilateral rupture of tubes was rare . in 5 out of 19 cases in a review of secondary bilateral ectopic pregnancy , unilateral tubal rupture in operative field\nbilateral unruptured tubal pregnancy in ampulary portion of tubes was seen . in our case ,\nleft tube was more distended , about 5 cm and right tube was 2 cm . in the review of bilateral tubal gestation in literature including primary and secondary cases , left tubal pregnancy was larger and more prone to rupture in comparison to right one .\nan attempt was made to review cases of medical literature which the side and size of rupture in bilateral tubal gestation was defined ( table 1 ) . medical treatment of these patients is not fully studied when pre - operative diagnosis is made .\nthere are three surgical approaches for ectopic pregnancy : salpingotomy , salpingostomy and radical salpingectomy . regarding the future plan of fertility procedures , conservation or resection of fallopian tubes\nmight be planned in the operation field ( 1 , 2 , 810 ) . in this case ,\nsize of right and left tube distention according to surgical findings in cases with bilateral ectopic pregnancy\nbilateral ectopic gestation , although rare , should be regarded as the differential diagnosis for ectopic pregnancy , especially in assisted reproductive technology cases and high titers of -hcg ( more than 100000 ) .\nleft tubal side of bilateral tubal pregnancy was more probable to rupture and it revealed bigger size in review of cases .", "answer": "backgroundbilateral ectopic pregnancy is a rare condition and is divided in two subgroups , primary and secondary , based on history of assisted reproductive technology.case presentationa 30 year old primigravid woman with history of infertility and ovulation induction presented to a hospital in kashan in year 2013 . \n she had vaginal bleeding , abdominal pain and ultrasound findings suggested early pregnancy . due to high titer of -hcg , gestational trophoblastic disease was proposed and d8c was done in referral and admission to gyneco - oncology ward in tehran . \n repeat sonography suggested ectopic pregnancy in left side and repeat -hcg level showed an increase of 19435 miu / ml . \n laparotomy findings revealed bilateral ampullary ectopic pregnancy . \n bilateral salpingostomy followed by one course of methotrexate was prescribed.conclusionbilateral ectopic gestation should be considered as a rare differential diagnosis for ectopic pregnancy . in this study , \n bigger size and rupture in left side was observed .", "id": 601} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prevalence of \n newborns with hyperthyrotropinemia was 1 in 8,000 live births at the beginning of neonatal screening in 1979 \n ( 1 ) , and it is now 1 in 2,500 births ( 2 ) in japan . due to the increase in the prevalence of screening - positive newborns ,\nthe number of \n newborns diagnosed as having transient hypothyroidism or transient hyperthyrotropinemia has increased .\nit has \n been reported that about 30% of screening - positive newborns with anatomically normal thyroids have transient \n forms of the disorder ( 3 ) .\nthe causes of transient hypothyroidism or \n transient hyperthyrotropinemia include prematurity , maternal thyroid disease and excess or lack of maternal \n iodine intake ( 4 ) . on the other hand\n, it has been reported that \n subclinical hypothyroidism persists in late childhood in about 30% of children found to be false - positive during \n neonatal screening ( 5 ) .\nit is unclear whether transient thyroid dysfunction and subclinical hypothyroidism represent true clinical \n conditions .\nthe aim of this study was to determine whether transient thyroid dysfunction and subclinical \n hypothyroidism detected during neonatal screening are influenced by genetic background .\nthe tsh receptor ( tshr ) , \n thyroid peroxidase ( tpo ) and dual oxidase 2 ( duox2 ) genes , for which it has been reported heterozygous defects \n cause neonatal transient thyroid dysfunction , were analyzed in children with transient thyroid dysfunction or \n subclinical hypothyroidism detected during neonatal screening .\nwe recruited nine screening - positive children who had not received levothyroxine ( l - t4 ) replacement or had been \n able to stop l - t4 replacement after re - evaluation of thyroid function .\nsubjects with known underlying causes of \n transient thyroid dysfunction , such as prematurity , down syndrome , maternal thyroid disease and excessive \n maternal iodine intake , were excluded .\nthey were continuously observed at toho university omori medical center \n or ibaraki children s hospital .\nthe study was performed with the approval of the institutional review boards of the toho university school of \n medicine and ibaraki children s hospital , and informed consent for participation in this study was obtained from \n all the subjects parents .\nall exons of the tshr \n gene , tpo gene and duox2 gene were amplified by polymerase chain reaction ( pcr ) using primers described in \n previous reports ( 6,7,8,9 ) .\nthe purified pcr products were \n sequenced directly by an automated dna sequence analyzer ( abi 310 autosequencer , applied biosystems , foster \n city , ca , usa ) .\nbasal tsh levels above 5 u / ml were considered elevated ( 5 ) , and peak tsh \n levels after trh stimulation above 35 u / ml in infants and above 2530 u / ml in children were considered \n exaggerated responses ( 10 , 11 ) .\nthe serum tsh level was 24.3 11.2 u / ml ( n=8 ) during neonatal screening .\nthe serum tsh and free t4 levels \n during the first visit to the hospital at 27 16 d of life were 14.3 8.0 u / ml ( n=9 ) and 1.52 0.25 ng / dl \n ( n=8 ) , respectively ( table 1 ) .\nfour children had not \n received l - t4 replacement , but their thyroid functions had been evaluated every 6 to 12 mo .\nalthough subject 8 \n showed normal serum tsh and t4 levels ( 4.19 u / ml and 10.9 g / dl , respectively ) during her first visit to the \n hospital at 56 d of life , her serum thyroglobulin ( tg ) level ( 120 ng / ml ) was slightly high .\nthe remaining five children started l - t4 replacement during the neonatal \n period and stopped it after re - evaluation of thyroid function at the age of 5.5 2.2 yr .\nafter the cessation of \n l - t4 replacement , their thyroid functions were evaluated every 6 mo .\nthe initial dose of l - t4 replacement was \n 3.2 0.5 g / kg / d , and the dose of l - t4 replacement at cessation was 1.0 0.2 g / kg / d ( table 2 ) .\nno \n patients had a family history of thyroid diseases.table 1 subjects initial thyroid function resultssubjectsexserum tsh level at screening ( u / ml)at first visit to the hospitalinitial dose of levothyroxine ( l - t4 ) \n ( g / kg / d)age ( d)basal tsh level ( u / ml)ft4 ( ng / ml)tsh peak after trh stimulation ( u / ml)1f42.01217.961.7190.713.42f15.41711.881.5948.762.63f14.5545.51.2nano treatment4f26.11832.781.75na3.05m14.51214.321.0952.913.86m43.41119.051.8546.623.07m20.33811.581.42nano treatment8fna564.19nanano treatment9m17.92011.81.2nano treatmentna : not available . \n table 2 subjects follow - up thyroid function resultssubjectagegenetic defectbasal tsh level under no treatment \n ( u / ml)at re - evaluationagetsh peak after trh ( u / ml)dose of l - t4 ( g / kg / d)16yr , 5moa single tshr mutation ( r450h)3.206.004yr , 0mo43.71.028yr , 4mond1.402.806yr , 6mo21.70.938yr , 4mond2.98nano treatment48yr , 6mond2.502.607yr , 2mo18.41.359yr , 3mond2.106.605yr , 6mo29.10.8610yr , 4mond1.401.909yr , 0mo20.71.0714yr , 1mond1.206.550yr , 8mo26.9no treatment814yr , 3moa single tpo mutation ( p883s)3.016.1110yr , 8mo30.2no treatment915yr , 0mond1.305.001yr , 5mo22.5no treatmentnd : not detected , na : not available . nd : not detected , na : not available .\nultimately , subjects 1 , 5 , 7 and 8 were diagnosed as having subclinical hypothyroidism because of fluctuating \n basal tsh levels during the no treatment period and/or exaggerated tsh responses to trh simulation at \n re - evaluation . all subjects with subclinical hypothyroidism were negative for anti - tpo and anti - tg antibodies . \n\nsubjects 2 , 4 and 6 were diagnosed as having neonatal transient hypothyroidism because they showed normal tsh \n responses to trh stimulation at re - evaluation and their basal tsh levels had been normal after cessation of l - t4 \n replacement .\nsubjects 3 and 9 were diagnosed as having transient hyperthyrotropinemia because they had not \n received l - t4 replacement and their basal tsh levels had been normal since the early infantile period .\nsubject 1 was heterozygous for a tshr gene mutation ( r450h ) , and subject 8 was heterozygous for a tpo gene \n mutation ( p883s ; fig .\n1 sequence analysis of a tshr gene in subject 1 \n ( a ) and a tpo gene in subject 8 ( b ) . (\na ) the mutant site ( g to a ) is indicated by the arrow .\n( b ) the mutant site ( c to t ) is indicated by the arrow . \n\nsequence analysis of a tshr gene in subject 1 \n ( a ) and a tpo gene in subject 8 ( b ) .\n( a ) the mutant site ( g to a ) is indicated by the arrow .\n( b ) the mutant site ( c to t ) is indicated by the arrow . \n\none group \n consists of genes causing thyroid dysgenesis , and the other group consists of genes causing thyroid \n dyshormonogenesis ( 12 ) . among them , tshr , sodium iodine symporter ( nis ) , \n tg , tpo and duox2 gene defects have been occasionally reported to cause mild hypothyroidism .\nsubjects who are \n heterozygous for tshr gene mutations have been reported to show various phenotypes , from euthyroid to mild \n hypothyroidism ( 13,14,15,16 ) .\nsome subjects with \n heterozygous tshr gene mutations were identified during neonatal screening , and the others were identified in \n the course of evaluation for common nonspecific symptoms .\nsubjects with biallelic inactivating mutations of the \n nis gene and tg gene have also been reported to show various phenotypes , from euthyroid to severe hypothyroidism \n ( 17,18,19,20 ) .\nreported that the \n heterozygous carrier rate for tpo gene mutations is significantly higher in babies with neonatal transient \n hypothyroidism than in normal babies and suggested that the presence of heterozygous tpo gene mutations \n contributes to development of neonatal transient hypothyroidism ( 21 ) . \n\nseveral reports suggest that biallelic inactivating mutations in the duox2 gene are associated with severe and \n permanent congenital hypothyroidism and that heterozygous mutations of duox2 gene are associated with neonatal \n transient hypothyroidism ( 9 , 22 ) . \n\nhowever , maruo et al . reported that subjects with compound heterozygous duox2 mutations \n detected during neonatal screening also showed transient hypothyroidism ( 23 ) . in the present study , the tshr , tpo and duox2 genes were analyzed because monoallelic mutations of these genes \n might cause transient neonatal thyroid dysfunction .\ntwo of nine children with transient thyroid dysfunction or \n subclinical hypothyroidism detected during neonatal screening had heterozygous gene mutations , one for a tshr \n gene ( r450h ) and one for a tpo gene ( p883s ) .\nthe r450h mutation of the tshr gene is common in japan ( 15 ) , and the p883s mutation of the tpo gene has been reported in japanese \n patients ( 24 ) . since nis and tg genes were not analyzed in the present \n study , some of the remaining seven children may have had mutations of these two genes .\nalthough further \n examinations are necessary , genetic background may contribute to development of the transient thyroid \n dysfunction and subclinical hypothyroidism detected during neonatal screening .\nthyroid function is influenced by several factors , such as general condition , age and amount of iodine intake . \n\nit is well known that patients with subclinical hypothyroidism can develop overt hypothyroidism during puberty \n and pregnancy due to the increase in thyroid hormone requirement .\nhowever , large amounts of iodine intake have been reported to cover the development of \n hypothyroidism in patients with biallelic inactivating mutations of the nis and duox2 genes ( 17 , 25 ) .\nmoreover , it has been \n reported that , if left untreated , goiters caused by elevated tsh stimulation in patients with defects of the tpo \n gene and tg gene are prone to development into thyroid cancer ( 26 , 27 ) .\ntherefore , it is important to continue long - term follow - up of children \n with transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening to avoid \n missing the development of overt hypothyroidism and goiters , given that they may have background gene \n defects . in conclusion ,\ntwo of the nine screening - positive children who had not received l - t4 replacement or had been \n able to stop the treatment had genetic mutations .\nit is possible that genetic background contributes to the \n development of transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening . \n\ntherefore , long - term follow - up of screening - positive children is required .", "answer": "about 30% of children with elevated tsh levels during neonatal screening have a transient form of disorder . \n on the other hand , it has been reported that subclinical hypothyroidism persists in late childhood in about \n 30% of children found to be false - positive during neonatal screening . \n the aim of this study was to determine \n whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are \n influenced by genetic background . \n the tsh receptor ( tshr ) , thyroid peroxidase ( tpo ) and dual oxidase 2 ( duox2 ) \n genes , for which it has been reported that heterozygous defects cause neonatal transient thyroid dysfunction , \n were analyzed . \n nine children with transient thyroid dysfunction or subclinical hypothyroidism detected during \n neonatal screening were studied . \n one child was heterozygous for a tshr gene mutation ( r450h ) , and another \n child was heterozygous for a tpo gene mutation ( p883s ) . \n no children with mutation of the duox2 gene were \n identified . \n genetic background may contribute to development of transient thyroid dysfunction and subclinical \n hypothyroidism detected during neonatal screening .", "id": 602} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe transversus abdominis plane ( tap ) block provides effective post - operative analgesia after abdominal surgery .\nrafi first described tap block , who injected local anesthetic through the ilio - lumbar triangle of petit within the tap between the internal oblique muscle and transversus abdominis muscle utilizing the double - loss of resistance technique .\nvirtually , the ultrasound - guided tap block is highly effective and easy technique for rendering analgesia for post anterior abdominal incision as supported by literature ; however , it can also be used as a sole anesthetic technique for abdominal surgeries where the autonomic innervation is partly or not involved .\na 67-year - old woman , 55 kg was admitted to hospital with a 3-day history of abdominal pain , nausea and vomiting .\nshe was diagnosed to have chronic obstructive pulmonary disease ( copd ) 5 years ago and had four episodes of prior hospitalization secondary to acute exacerbation .\nshe often required nebulisers and had an exercise tolerance of approximately 100 yards . in the week prior to admission she had received oral antibiotics and steroids for an infective exacerbation of copd . on admission to the hospital she had signs of peritonitis and her abdomen\nexamination revealed reduced bi - basal air entry with crepitations all over the chest and chest x - ray showed consolidation of the right middle and lower lobe .\nher arterial blood gas revealed type i respiratory failure ( fio2 0.60 , ph 7.37 , po258 mmhg , pco245 mmhg ) .\nintravenous acetaminophen was administered for pain relief , but despite this she could not cough or take deep inspiration due to ongoing pain .\nshe was categorized as american society of anesthesiologists ( asa ) physical status grade iv / e and was planned for emergency laparotomy .\nwe planned to avoid general , epidural or spinal anesthesia , so we opted for tap block under ultrasound guidance as a sole anesthetic technique .\nafter proper explanation to the patient about the technique of tap block , she was taken to operation theatre table and monitors attached .\nhence oxygen supplementation was carried out with venturi mask with oxygen flow at 6 l / min .\nsaturation improved to 92% . after securing an iv access with 18 g ( gauge ) needle on the right dorsum of the hand ,\nshe was sedated with intravenous dexmedetomidine infusion at 4 mcg / kg / min to make her comfortable , cooperative , and pain free for performing the block .\nthen she was laid supine with the anterolateral abdominal wall exposed bilaterally from the iliac crest to the sub - costal margins and scrubbed aseptically .\nthe block was performed using an aseptic ultrasound guided in - plane technique ( s - nerve sonosite , hfl38 ( company brand name of the 6.0 to 13.0 mhz linear probe ) probe , 100 mm sonoplex needle ) . when the needle tip position is within the tap neuro - fascial plane a mixture of 20 ml of 0.25% bupivacaine , 20 ml of 1% lidocaine and 0.2 mg adrenaline\na remarkably good clinical effect was achieved within 30 min with almost complete resolution of pain .\nshe made a slow post - operative recovery to be discharged from hospital 14 days after admission .\nthe use of tap blocks for control of post - operative analgesia has been described following a variety of abdominal operations such as appendectomy , hernia repair , caesarean section , abdominal hysterectomy , and prostatectomy etc .\nbilateral blocks can be given for midline incisions or laparoscopic surgery with careful safe dosing .\nto our knowledge , the use of ultrasound - guided bilateral tap for a sole anesthetic technique for upper abdominal surgery in a very high - risk patient has been rarely reported . the skin , muscles and parietal peritoneum of the anterior abdominal wall are innervated by the lower six thoracic nerves and the first lumbar nerve .\nafter leaving the respective intervertebral foramina the anterior rami ( sensory afferents ) of these nerves course around the transverse process , then pierce the musculature of the lateral abdominal wall to course through a muscle neurovascular plane superficial to the transversus abdominis . in the midaxillary line ,\nthe sensory afferents branch out as a lateral cutaneous branch and continue within the tap to perforate anteriorly supplying the skin as far as the midline .\nthe tap plane thus provides a space into which the local anesthetic can be deposited to achieve myocutaneous sensory blockade .\nwhilst early studies showed a t7 to l1 spread with a single posterior injection making the block suitable for midline abdominal incisions , other studies , however , failed to demonstrate a spread cephalad to t10 making it more suited for lower abdominal surgery . in a small cadaveric study , t11 , t12 , and l1 were most consistently present in the tap while t10 was present in 50% of the cases .\nhowever , augmentation with a subcostal injection will help attain a higher block up to t7 which is a modification of the original technique in which the ultrasound probe is placed just beneath the costal margin and parallel to it .\nthe needle is then introduced from the lateral side of the rectus muscle in the plane of the ultrasound beam and 10 ml of local injected into the tap to extend the analgesia provided by the posterior tap block above the umbilicus . in our patient bilateral ,\nsub - costal tap block under ultrasound guidance resulted in highly effective myocutaneous sensory blockade .\nas the patient was categorized as asa iv / e general anesthesia or central neuraxial blockade for the emergency operation for such a high - risk case would have resulted in untoward and fatal complications both intra - operatively and postoperatively .\nthe abdominal wall sensory afferents , which course through the tap plane could be blocked successfully and effectively by abdominal field blocks or tap block under ultrasound guidance then the abdominal incision and operation could be carried out without patient 's discomfort .\npain caused by visceral stimulation of the celiac plexus may still challenge intraabdominal surgical success which is a major limitation .\nwhen the surgeons manipulated the intestine , the patient complained of pain due to stimulation of autonomic nervous system through celiac plexus ( vagus ) , but dexmedetomidine infusion helped in relieving the pain or retching sensation .\nanatomically , sympathetic and somatic innervation are closely related near the neuraxis , but become separated peripherally .\nthus , spinal , epidural or paravertebral blocks will cause significant sympathetic block , resulting in major cardiovascular changes and other physiological effects . on the other hand ,\nif complete denervation of viscera is required , vagal afferents have to be blocked by celiac plexus block .\nthe extent and spread of the local anesthetic solution in the tap affecting anterior abdominal wall sensory afferents depend on time factor .\nit seems that the full effect of analgesia takes at least 20 - 25 min after injection of local anesthetic solution .\nmcdonnell et al . suggest that local anesthetic spreads within the tap plane progressively over the several hours and an early assessment of the extensive tap block may be missed .\nas ultrasound - guided bilateral transversus abdominais neurofascial plane block is quite simple , quick , safe , and effective especially for a very high - risk patient with multi - medical problems and geriatric patients needing an elective or emergency abdominal surgery , the surgeons and anesthesiologists should encourage this technique , even in this advanced era , when it is deemed suitable .", "answer": "although transversus abdominis plane ( tap ) block is an effective way of providing analgesia in post - operative abdominal surgery patients ; however , it can be considered as an anesthetic technique in high - risk cases for surgery . \n we report a case of a geriatric female with chronic obstructive pulmonary disease in the respiratory failure , hypotension , posted in an emergency with old perforation leading to peritonitis . \n the surgery was successfully conducted under bilateral tap block , which was used as a sole anesthetic technique . \n tap block can be considered as an anesthetic technique for abdominal surgery in moribund patients .", "id": 603} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthough rare , it can lead to neurological sequelae such as bowel and bladder dysfunction , sexual dysfunction , saddle anesthesia , sciatica , and motor weakness .\nhematoma is a good culture medium for bacteria ; therefore , reducing hematoma is advantageous in reducing infection .\nmany surgeons consider that a surgical drain increases the postoperative infection rate2561821 ) . as a foreign body\nis inserted into a patient , it can lead to local inflammatory responses and can activate host defense system ; alternatively , it can act as an inlet of infection .\ntherefore , there is a controversy about usefulness of surgical drain in single - level lumbar disc surgery and that bleeding is not much . in this study\nwe studied 70 patients who had undergone single - level lumbar discectomy from april 2011 to march 2012 .\nthe patients who had undergone multilevel surgery , fusion surgery , and/or previous lumbar surgery were not included in this study .\nthis study was based on retrospective analysis of the patients ' medical records that included their age , sex , diagnosis , level of surgery , mean operation time , length of stay after surgery , past history ( hypertension and diabetes ) , and smoking or not , levels of c - reactive protein ( crp ) , and scores of visual analogue scale ( vas ) .\nthe patients were divided into 2 groups : one that received the surgical drain and the other that did not .\nthere were 42 patients who received the drain that included 21 men and 21 women with mean age of 49.93 years , and there were 28 patients who did not receive the drain that included 13 men and 15 women with mean age of 43.86 years .\nboth groups received prophylactic antibiotics ( 1st generation cephalosporin ) intravenously for 7 to 8 days .\nwe checked the levels of crp on postoperative days 1 , 3 , and 5 .\nthe amounts of surgical drainage collected for 24 hours were checked daily at the same time . in drainage group ,\nproximal tip culture of surgical drain was conducted when removed . between postoperative days 7 and 8 ,\nwe compared the rates of infection , the levels of crp , and the scores of vas in preoperative , postoperative , and the first postoperative follow - up phases at the outpatients department .\nthe demographics of the 2 groups were compared using t - test and fisher exact test .\nthe mean duration of the surgical drain and the mean of total amounts of drainage were 2.88 days and 71.57ml , respectively .\nthe daily amounts of drainage on the postoperative days 1 , 2 , and 3 were 35.4 , 20.8 , and 14.27ml , respectively ( fig .\nthe differences in the levels of crp between the 2 groups were not significant ( p>0.05 ) ( fig .\n2 ) . the mean level of crp in drainage group on postoperative days 1 , 2 , and 3 were 4.17 , 3.76 , and 2.41mg / l and in nondrainage groups mean level of crp were 4.89 , 5.2 , and\nthe differences in the scores of vas in preoperative , postoperative , and follow - up phases were not significant between the 2 groups ( p>0.05 ) ( fig .\n3 ) . the mean scores of vas in the drainage group in preoperative , postoperative , and follow - up phase were 7.5 , 2.64 , and 0.64 and mean scores of vas in the nondrainage groups were 7.28 , 2.1 , and 0.76 .\nthe mean length of hospital stay after surgery was 9.68 days ; further , it was 8.68 days in the drainage group and 9.87 days in the nondrainage group .\nthe mean operation time of the drainage group was longer than the nondrainage group ( 150.2 minutes vs. 130.8 minutes ) .\nbut there was no significant difference between the 2 groups ( p>0.05 ) . in the group that did not receive surgical drain ,\nthe mean operation time of infected patients was 100 minutes and that of no infection patients was 144.5 minutes .\nthe operation time of infected patients was shorter than no infection patients , but there was no significance ( p>0.05 ) .\nthere was no statistically significant difference between the 2 groups ( p=0.157 ) ( tables 1 , 2 ) .\none of the 2 infected patients in the group that did not receive surgical drain was a 39-year - old woman who had undergone left l5-s1discectomy .\nafter 13 days of operation , she had fever and pus - like discharge at the operated site .\nshe underwent a repeated surgery on postoperative day 14 and received antibiotics treatment for 6 weeks ( fig .\nthe other patient was a 53-year - old woman who had undergone right l4-l5 discectomy .\nthe lumbar magnetic resonance imaging ( mri ) revealed fluid collection with rim enhancement at the operated site and adjacent soft tissue enhancement was also observed .\nshe underwent a repeated surgery on postoperative day 13 and received antibiotics treatment for 6 weeks .\nthe intraoperative pus culture grew methicillin - resistant and coagulase - negative staphylococcus ( fig .\nthe incidence of symptomatic epidural hematoma is rare ; however , the overall incidence rates of epidural hematomas on the first postoperative day of lumbar decompression surgery were reported using mri to be as frequent as 86%12 ) .\npostoperative surgical drain can not only reduce the incidence and severity of hematoma formation but can also reduce the postoperative fibrosis14 ) .\nthe incidence of postoperative infection can be less than 1% after decompressive operation and more than 10% after fusions15 ) . in this study\n, we analyzed the relation between the surgical drainage and postoperative infection in 70 patients who had undergone single - level lumbar disc surgery .\nthere were 2 cases of postoperative infection and both of them did not receive surgical drains ; however , there was no statistical significance . additionally , there was no significant difference in the outcomes of surgery ( pain and length of hospital stay after surgery ) .\nadditionally , from the financial perspective , there was no significant increase in the length of hospital stay because of surgical drain .\nthe difference in the infection rates of the 2 groups ( one that received the surgical drains and the other that did not ) was not statistically significant .\nalthough many surgeons consider that surgical drain insertions increase infection rate , many studies have also shown no increase in the infection rate of surgical drains34816 ) .\nkanayama et al.8 ) studied drain use after single - level lumbar decompression surgery and found \" wound infection was not influenced by use of a drain . \" more recently , poorman et al.17 ) studied drain use in cervical surgery and concluded \" no differences in incidence of complications . \" ho et al.7 ) reported significant increase the incidence of delayed postoperative infection in patients who did not received surgical drains .\nthough it may not always be correct , the tip cultures of surgical drains can allow us to detect postoperative infection at an early stage , and it can lead to faster initiation of antibiotics treatment10111920 ) .\npositive tip culture predicts wound infection in 50% and a negative culture virtually excludes the possibility of a deep infection .\nkobayashi et al.11 ) studied the efficacy of use of drain tip culture and conclude \" rain tip culture is useful for early detection of surgical site infection caused by methicillin resistant bacteria . \" in their series , there were 34 cases of positive tip culture and there were 19 surgical site infections .\ndrain tip culture had a sensitivity of 52% , specificity of 92% and the association between positive tip culture and wound infection was significant ( p<0.05 ) . in our study , the patients who underwent postoperative infection may have an opportunity to detect it earlier if they received drain tip culture .\nsurgical drains can reduce the risk of hematoma formation and can detect postoperative infection early by conducting drain tip culture .\nhowever , even though simple , inserting surgical drain require additional effort of medical worker , time , cost of material , postoperative care and patient 's discomfort .\nthe decision to use or not a surgical drain is left to the surgeon 's discretion but using surgical drain can be considered in patient who has bleeding tendency and who has susceptibility to infection .\nalthough many surgeons are apprehensive about postoperative infection by surgical drainage , no increase in infection rate and no difference in wound healing or postoperative neurological deficit have been observed .\nthe tip cultures of surgical drains can be an effective means of detection of the postoperative infection", "answer": "objectivesurgical drains are commonly used after the spine surgeries for minimizing hematoma formation , which can delay wound healing and may become a source of fibrosis , infection , and pain . \n the drain , however , may provide a direct route for infection if it is contaminated . \n our objective was to survey the relationship between surgical drains and infection.methodsthe 70 patients who had undergone single - level lumbar discectomy from april 2011 to march 2012 were retrospectively analyzed . \n each patient 's medical chart and magnetic resonance image were thoroughly reviewed after all the patients had been divided into the drainage and the nondrainage groups . \n the amounts and durations of the surgical drains in the drainage group were analyzed . \n additionally , the levels of c - reactive protein , rates of infection , scores of preoperative and postoperative visual analog scale ( vas ) , and lengths of hospital stay after operation were compared between the 2 groups.resultsin this study , 70 patients were retrospectively analyzed ; out of which , 42 and 28 patients were included in the drainage and the nondrainage groups , respectively . \n two of the postoperative infection cases in the nondrainage group required to undergo repeated operations . \n the frequency of the postoperative infection cases was higher in the nondrainage group than in the drainage group ; however , there was no significant statistical difference between the 2 groups ( p=0.157).conclusionsurgical drains did not elevate postoperative infection . \n furthermore , drain tip cultures allowed us to detect postoperative infection at an early stage , and it led to faster initiation of antibiotics treatment .", "id": 604} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe relationship between the clotting cascade and the promotion or inhibition of the anti - inflammatory response continues to be defined through basic research .\nthe potential key role of proteins that were originally believed to be exclusively involved in coagulation in the inflammatory response provides an exciting potential mechanism(s ) for modification through the application of new therapies .\nthe accompanying review by riewald and ruf outlines the available information on the possible steps involving some of the various proteins that are common to both coagulation and inflammation .\nthe complexity of the multiple actions of the proteins in both inflammation and coagulation should excite the clinician with regard to potential new therapies that may be beneficial via activation of one or both of the concurrent pathways .\nhowever , before clinicians can administer new therapies that utilize new knowledge on the actions of coagulation cascade components , and hence improve the outcomes of their patients , several gaps in our current understanding must be addressed .\nthis information is imperative if the clinician is to take basic knowledge ' to the bedside ' , where individual patients can benefit .\nadministration of intrinsic or synthetic analogues of coagulation cascade components ( e.g. protein c , thrombin , and factor viia or xa ) , coagulation inhibitors ( e.g. heparin or analogues ) , or agonists or antagonists of the protease - activated receptors , in an attempt to alter the individual patient 's coagulation / inflammation balance , could theoretically produce responses ranging from beneficial to detrimental .\nknowledge of the ' most beneficial ' balance between augmenting or inhibiting the contribution of the clotting cascade components to inflammation would be required for determining the selection and dosing of potential new therapies .\na safe assumption is that any new therapies that alter the intrinsic response to coagulation and inflammatory stimulants would also potentially produce detrimental effects on these , and potentially other , physiological responses .\na simple example of such a potential for detrimental effects is the administration of protein c resulting in undesirable haemorrhage .\nthis example illustrates that a broader knowledge of the impact of altering the coagulation/ inflammatory response will be required before clinicians can comfortably utilize new therapies in patient care .\nit is unlikely that any new therapies resulting from the new knowledge of the contribution of the clotting cascade to inflammation can be applied to all patients .\nit can be anticipated that certain patients would have contraindications to the new therapies or that dosages would need to be adjusted on the basis of pharmacokinetic or pharmacodynamic variables .\nthe clinician will need to know what these contraindications and variables are before the new therapies can be used confidently .\nsome , such as coagulation disorders , may be known and obvious , but any new strategies that could potentially alter the balance of a complex physiological response may be anticipated to be influenced by many , as yet unknown , factors in the individual patient .\nan example is the concurrent administration of heparin , which appears to antagonize the anti - inflammatory effect of antithrombin iii in septic patients .\na more complete understanding of the impact of concurrent conditions , therapies and the patient 's genetic make - up on outcome will be required if we are to obtain the maximum benefit from new therapies .\nfor any new therapy resulting from our expanded knowledge of the clotting cascade in the inflammatory response to be tailored to the needs of the individual patient , a method(s ) for rapidly and easily assessing the patient 's dynamic inflammatory response will be required .\nunless any new therapies have very benign toxicities , the need to assess the need , dosage and response to treatment will mandate sensitive and specific monitoring techniques .\nbedside or clinical laboratory techniques that could be applicable to most clinical environments would allow the benefit of any new therapies to be applied to the greatest number of patients .\nconversely , any new treatments that require complex , laborious monitoring techniques will have limited applicability .\nas our knowledge of the contribution of the intrinsic coagulation components increases , the development of many potential new therapies will hopefully emerge for clinical use\n. these may be totally new therapeutic entities or new strategies for using existing drugs or clotting factors .\nsuch developments will create the new dilemma for the clinician , namely that of trying to select between different treatment options for the individual patient .\nclinical trials outlining the potential anticipated benefit(s ) and the appropriate target patient population for each new therapeutic strategy will need to be completed\n. this will allow the clinician to ensure that the most appropriate strategy can be selected for the individual patient .\nthe above - mentioned concerns aside , the clinician should be excited about the expanding knowledge of the role of coagulation cascade components in modifying the inflammatory response\n. such knowledge will hopefully result in new strategies and therapies to manage the septic patient .", "answer": "the relationship between blood coagulation factors and the promotion or inhibition of the anti - inflammatory response continues to be defined through basic research . \n the potential key role of blood coagulation factors in the response during sepsis provides an exciting potential mechanism(s ) for modification through the application of new therapies . \n the complexity of the potential multiple actions of the proteins , such as protein c , should allow for development of new therapies to minimize the detrimental inflammatory response . \n however , several gaps in our current understanding must be bridged before the clinician can take the basic knowledge ' to the bedside ' , where individual patients will benefit .", "id": 605} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfor the invasive treatment of symptomatic aortic stenosis several attractive options became available beyond conventional cardiosurgical implantation of stented bioprostheses or mechanical valves . besides stentless prostheses , in particular transcatheter procedures are of growing importance . \nnevertheless the number of implanted stented bioprostheses in germany expanded or at least remained stable over the last years .\nthus , 9.704 bioprostheses were implanted in germany in 2010 , according to 84% of all implanted prostheses in aortic position .\nimplantation of bioprostheses was associated with a 30-day - mortality of 3,3 % , which is higher than for mechanical valves ( 1,5% ) due to the fact that patients for bioprostheses are significantly older or suffer from more complex co - morbidities . \nthe purpose of this review is to summarize the features of the currently available bioprostheses in the light of competing procedures .\nthere has been a continuous development to improve the design of stented bioprostheses with respect to hemodynamic profile , biological durability and ease of implantation .\nvarious designs are available , allowing a valve selection according to individual patient factors or anatomical criteria including techniques for intra - annular and supra - annular positioning [ 3 , 4 ] .\nit would have the same biological and hemodynamic properties as a normal valve and would not undergo degeneration .\nstented bioprostheses have proven to be effective even in small aortic roots regarding hemodynamic improvement , left ventricular mass reduction and improvement of the patient s quality of life . in vitro examinations showed pericardial valves to be slightly superior to porcine valves with regard to gradient and orifice area .\nassociated with the scalloped designs of stented bioprostheses a tension - free implantation with avoidance of paravalvular leaks can be expected . \nimplantation techniques evolved over the last decades which resulted in short cross - clamp times in normal findings .\nsurgeons learned that meticulous care in decalcifying the aortic annulus and sizing helps to prevent paravalvular leaks .\nadditionally , accurate sizing prevents a patients - prosthesis - mismatch which could result in poor postoperative clinical performance . avoiding the use of running suture for stented valve implantation\nthe evolvement of low profile valves reduces the risk of coronary occlusion in patients with a small distance between annulus and coronary ostia .\nthe currently available and established bioprostheses show rates of degeneration at 20 years around 15% in patients aged 65 or higher . the freedom from repeat aortic valve replacement reaches over 85% after 20 years in patients older than 60 years and 65% in all age groups . along with these convincing results of durability and freedom of re - implantation stented bioprostheses became also attractive for younger patients .\nif a repeated valve replacement is necessary due to functional deterioration the operative mortality is acceptable with 4 to 6% and is mainly due to active endocarditis and comorbidities . \nlately transcatheter aortic valve implantation ( tavi ) with valve - in - valve implantation into the degenerated xenograft showed to be an additional option in high risk patients with the need for redo valve replacement .\nstentless porcine valves were initially believed to have superior hemodynamic properties resulting in more effective reduction of left ventricular mass and better clinical performance according to nyha class .\nthese findings could nt be yet approved by long - term follow up investigations [ 15 , 16 ] .\nbearing this in mind calls the more demanding implantation technique of stentless prostheses in question .\nstented bioprostheses are still used more commonly than stentless ones because of their relative ease of implantation , their extensively documented long - term results , and the low risk associated with reoperation . \nanother biological approach is the use of an autograft like the ross procedure , where the patient s pulmonic valve is transferred to the aortic position .\nthese pulmonic autografts have excellent hemodynamic properties as well as low rates of thrombosis , degeneration , and endocarditis .\nthe ross procedure is suitable for children and young adults because it is compatible with further growth of the aortic root .\nnevertheless since the pulmonary valve has to been replaced by a bioprosthesis it is a demanding two valve procedure with prolonged cross clamping times . aside from this , special means are necessary for pulmonary autograft stabilization to prevent its degeneration .\nthere are only a few current randomized trials comparing the long - term results of biological and mechanical valves .\na large - scale review revealed no difference in survival rates at 10 years and a slightly higher survival rate at 15 years for patients with mechanical prostheses .\nthe reoperation rate for mechanical valves in the aortic position is less than 5% at 10 years and less than 10% at 15 years , while the corresponding figures for bioprostheses are 10% and 30% , respectively .\nhemorrhagic complications are significantly more common in patients with mechanical valves because of anticoagulation . \nchronic atrial fibrillation is no longer a contraindication to bioprostheses since permanent oral anticoagulation can be avoided if concomitant ablative surgery results in permanent conversion to sinus rhythm .\nend stage renal failure was also defined a contraindication to bioprostheses since a rapid degeneration was feared due to altered metabolism in these patients .\nit has been found that life expectancy is already curtailed to such an extent that bioprosthesis degeneration often does not occur in the remaining lifetime .\nthe supposed advantage of the longer durability of a mechanical valve is also offset by the potential complications of oral anticoagulation , especially because anticoagulation is more difficult to manage in dialysis patients than in others . \nnevertheless aortic valve replacement using a tissue valve remains controversial for patients younger than 60 years since there are studies reporting reduced mid - term results .\nsome younger patients are averse to oral anticoagulation and therefore prefer a biological valvular prosthesis .\nthus , younger patients opting for a bioprosthesis can enjoy a normal quality of life without anticoagulation for many years but may need to undergo a second valve replacement procedure with an acceptable degree of risk .\nimplantation of conventional prostheses can be performed through a limited direct access like a hemi - sternotomy or a lateral access . reported large series show that aortic valve operations can be safely performed in experienced centers .\nsubstantial progress in valve technology led to the development of self - expanding valves . since a few years a number of bioprostheses are available for suture - less implantation which is usually combined with a limited surgical access . \n. future will show the benefits of this procedure characterized by short cross clamping times and whether it can coexist with tavi procedures . \nafter its clinical inauguration by cribier in 2002 the transcatheter aortic valve implantation gained widespread use in high risk patients with aortic stenosis .\nin germany a massive increase of its application can be observed ; in 2010 nearly every fourth aortic valve replacement was performed as a tavi procedure .\nthe partner trial was a randomized trial comparing tavi with standard - of - care therapies in high risk patients .\na 2-year follow - up of patients in the partner trial supports lately tavi as an alternative to surgery in high - risk patients . \nthe two treatments were similar with respect to mortality , reduction in symptoms , and improved valve hemodynamics , but paravalvular regurgitation was more frequent after tavi and was associated with increased late mortality . \nthere are a growing number of publications reporting promising short term results in high risk patients .\nnevertheless there is still a lack of evidence that tavi is superior to open valvular replacement as the gold standard regarding long - term results . \ncurrent guidelines recommend the use of tavi restricted to patients with contraindications for open surgery or inacceptable perioperative risks .\ncurrent studies reveal that bioprostheses of the most recent generation last longer than earlier types .\nbecause life expectancies in general have risen , more and more elderly patients are presenting for valve replacement and for these patients a bioprosthesis is usually chosen .\nin addition the cost effectiveness of stented bioprostheses appears unbeatable and the surgical ease of implantation allows for cross - clamp times between 30 and 60 minutes .\noverall , even in face of more innovative biological alternatives the implantation of stented bioprostheses is still a very interesting option and represents actually the most frequent valve implantation technique for aortic stenosis . especially in the light of growing use of interventional valve replacement\nthere is the urgent need for complete nationwide registry with adequate long term follow up , quality of life information and relevant subgroup analysis to define new standards in the treatment of patients with aortic stenosis .", "answer": "introductionbiological stented prostheses are currently the main type of prosthetic valve used for aortic valve replacement . \n the ratio of bioprotheses to mechanical prostheses has switched in the last 15 years ; the percentage of biological prostheses implanted has risen from 30 % to 85 % . \n moreover the total number of implanted stented bioprostheses remained stable over the last years despite competing procedures like stentless prostheses or transcatheter aortic valve implantation.methodsa literature search of all published aortic valve replacement studies was performed from january 2000 through may 2012.resultsthe recommendations guiding the type of heart valve replacement have been revised in recent years . \n of particular interest are the new generation of biological prostheses with extended durability , a decrease in mortality of reoperation and an increase in life expectancy . \n comorbidities such as chronic renal insufficiency or chronic atrial fibrillation are no longer contraindications to bioprostheses.conclusionoverall , even in face of more innovative biological alternatives the implantation of stented bioprostheses is still a very interesting option and represents actually the most frequent valve implantation technique for aortic stenosis .", "id": 606} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npseudohypoparathyroidism ( php ) is a disorder of end - organ resistance primarily affecting the actions of parathyroid hormone ( pth)1 ) .\nit is characterized by hypocalcemia and hyperphosphatemia in association with increased secretion of pth due to decreased target tissue responsiveness to pth .\npatients with php ia are not only resistant to pth , but also to other hormones that bind to receptors coupled to stimulatory g protein ( gs alpha)2 ) .\nthe gnas gene is located on chromosome 20q13.11 and consists of 13 exons and 12 introns3 ) .\nphp - ia is caused by heterozygous mutations affecting one of the 13 gnas exons encoding gs alpha4 ) .\nwe report here a 9-yr - old boy with php ia with a nonsense mutation of c.637 c > t in the gnas gene , which is novel .\n9-year - old boy was admitted to hallym university medical center with painful subcutaneous soft tissue masses with calcifications on the right toes and posterior chest wall . he had a history of repeated convulsive episodes from the age of 2 months .\nphysical examination showed short stature ( 120 cm , 3rd percentile ) , round face ( fig .\n2 ) and subcutaneous ossifications on the 2nd toe tip and 1st web space of the right foot and the left lower posterior chest wall ( fig .\n3 ) . his weight was 30 kg ( 50th percentile ) , thus having a normal body mass index ( 20.83 kg / m , 85th-90th percentile ) .\nhe was born at full term by cesarean section with a birth weight of 3.3 kg .\nfamily history revealed that his maternal grandmother had features suggestive of aho , such as short stature , round face , obesity and brachydactyly .\nhis mother had normal appearance apart from short stature , but two of her siblings had short stature , round face and obesity .\nwe could not make further investigation because the patient lost contact with his mother and maternal family after his parents got divorced .\nlaboratory tests revealed hypocalcemia ( 4.2 mg / dl ; normal range , 8.8 - 10.8 mg / dl ) , hyperphosphatemia ( 8.9 mg / dl ; normal range , 3.7 - 5.6 mg / dl ) and elevated serum pth ( 146.5 pg / ml ; normal range , 9 - 65 pg / ml ) .\nhe also showed elevated plasma thyroid - stimulating hormone ( 6.978 iu / ml ; normal range , 0.5 - 4.8 iu / ml ) , follicle stimulating hormone ( 5.6 iu / ml ; normal range , 0.26 - 3.0 iu / ml ) , and luteinizing hormone ( 1.2 iu / ml ; normal range , 0.02 - 0.3 iu / ml ) , which suggest multiple hormone resistance .\nurinary phosphorous and cyclic adenosine monophosphate response after infusion of synthetic human pth ( teriparatide acetate ) was attenuated ( ellsworth - howard test ) ( table 1 ) .\nhis intellegence scale ( korean educational development institute - wechsler intelligence scale for children ) indicated mild mental retardation ( intelligence quotient , 67 ) .\nhe was diagnosed as having php ia based on physical and laboratory findings ; hypocalcemia , hyperphosphatemia , pth resistance , presence of aho , multiple hormone resistance and mental retardation .\nhe was started on phosphate - binding substance ( aluminum hydroxide , 80 mg / kg / day ) , vitamin d ( alfacalcidol , 1 mcg / day ) and calcium carbonate ( 50 mg / kg / day ) .\nthree months later , his serum calcium was elevated from 4.2 to 6.0 mg / dl , and phosphorus was decreased from 8.9 to 8.6 mg / dl .\nthe patient 's clinical symptoms of pain , seizure and hyperactivity were reduced . to support the diagnosis of php ia , we performed dna analysis of the gnas gene .\ngenomic dna was extracted from peripheral blood leukocytes using the wizard genomic dna purification kit following the manufacturer 's instructions ( promega , madison , wi , usa ) .\nall coding exons and their flanking introns of the gnas gene were amplified using primer sets designed by the authors .\npolymerase chain reaction was performed with a thermal cycler ( model 9700 , applied biosystems , foster city , ca , usa ) as follows : 32 cycles of denaturation at 94 for 30 seconds , annealing at 60 for 30 seconds , and extension at 72 of 30 seconds .\nafter treatment of amplicon ( 5 ul ) with 10 u shrimp alkaline phosphatase and 2 u exonuclease i ( usb co. , cleveland , oh , usa ) , direct sequencing was performed with the bigdye terminator cycle sequencing ready reaction kit ( applied biosystems ) on the abi prism 31001 genetic analyzer ( applied biosystems ) .\nsequencing of the amplified gnas genomic dna fragments revealed a heterozygous nonsense mutation within exon 11 ( c.637 c > t ) ( fig . 5 ) .\nthe c > t transversion results in an amino acid substitution from gln to stop codon at codon 213 ( p.gln213 ) . to our knowledge , this is a novel mutation in gnas .\nwe also performed dna sequencing of the gnas gene of his father , but no mutation was detected .\nphp is a heterogeneous disease characterized by pth resistance and classified as types ia , ib , ic , and ii , according to its different pathogenesis and phenotype5 ) .\nin contrast to the situation in hypoparathyroidism , in php the parathyroid glands are normal or hyperplastic and they can synthesize and secrete pth6 ) .\nheterozygous inactivating mutations within gs alpha - encoding gnas exons are found in patients with php - ia , who also show resistance to other hormones and a constellation of physical features called aho .\npatients who exhibit aho features without evidence for hormone resistance , who are said to have pseudopseudohypoparathyroidism ( pphp ) , also carry heterozygous inactivating gs alpha mutations1,7 ) .\nthere is some evidence to suggest that the gs alpha mutation is paternally transmitted in patients with pphp and maternally transmitted in patients with php - ia .\nthe gene may be imprinted in a tissue - specific manner6,8,9 ) . in our case ,\ndna sequencing of the patient and his father revealed that only the patient had mutations .\nthe presence of slight aho in the mother 's side of the patient may suggest that the mutation came from his mother , but we were unable to confirm this because the dna of the patient 's mother or maternal family was not available at the time of the study .\nalthough we could not obtain molecular data from the maternal family of the patient , considering variation of phenotypes due to genomic imprinting , we were able to explain that the patient had the genotype and phenotype of php ia . in the maternal family of the patient ,\nhis mother had milder features suggestive of aho , whereas her mother and two siblings had characteristics that were more strongly suggestive of aho .\nwe can suspect the possibility of a hypofunctioning gnas mutation like mosaicism , but it was impossible to validate .\nmutational analysis of gnas gene is a useful method for identifying genetic abnormalities as well as making diagnosis and differentiation of various subtypes of php10 ) .\nthere are previous reports of korean patients with php ia and pphp who were confirmed by genetic analysis .\npark et al.11 ) reported a nonsense mutation of c.94a > t ( p.k32x ) and a frame shift mutation of c.344_345inst ( p.v117rfsx23 ) in patients with php ia , of which the former was novel . in a study of patients with php ia and pphp , jin et al.10 ) identified two novel mutations ; c.569_570del mutation ( p.tyr190cysfsx19 ) and a splicing mutation ( c.659 + 1g > a ) .\ngnas has been termed one of the most complex gene loci in the human genome3 ) .\nalthough many mutations have been identified in gnas , c.637 c > t nonsense mutation is deemed novel .", "answer": "pseudohypoparathyroidism type ia ( php ia ) is a disorder characterized by multiform hormonal resistance including parathyroid hormone ( pth ) resistance and albright hereditary osteodystrophy ( aho ) . \n it is caused by heterozygous inactivating mutations within the gs alpha - encoding gnas exons . \n a 9-year - old boy presented with clinical and laboratory abnormalities including hypocalcemia , hyperphosphatemia , pth resistance , multihormone resistance and aho ( round face , short stature , obesity , brachydactyly and osteoma cutis ) which were typical of php ia . \n he had a history of repeated convulsive episodes that started from the age of 2 months . \n a cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation . \n family history revealed that the patient 's maternal relatives , including his grandmother and 2 of his mother 's siblings , had features suggestive of aho . \n sequencing of the gnas gene of the patient identified a heterozygous nonsense mutation within exon 11 ( c.637 c > t ) . \n the c > t transversion results in an amino acid substitution from gln to stop codon at codon 213 ( p.gln213 * ) . \n to our knowledge , this is a novel mutation in gnas .", "id": 607} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nemphysematous cystitis is a distinct complicated lower urinary tract infection ( uti ) characterized by air within the bladder wall and lumen .\npatients with chronic utis , indwelling urethral catheters , urinary tract outlet obstruction , or neurogenic bladders are predisposed to complicated utis such as emphysematous cystitis .\nair within the urinary tract can also occur due to instrumentation , fistula to a hollow viscus , tissue infarction with necrosis .\npatients might have varied presentations , ranging from incidental diagnosis on abdominal imaging to severe sepsis .\ngas - forming infections or emphysematous conditions of the urinary tract are potentially life - threatening , and require prompt evaluation and management .\nwe describe a case of emphysematous cystitis that was managed successfully with bladder drainage , intravenous antibiotics , and strict glycemic control .\na 45-year - old male who was a known case of type-2 diabetes mellitus for last 16 years , complained of on and off fever , dysuria and turbid colored urine for last 3 months .\nhe had past history of suprapubic catheterization for obstructive uropathy due to meatal stenosis 15 years back . clinical examination revealed pallor , penile hypospadias , meatal stenosis , bilateral nonproliferative diabetic retinopathy and evidence of sensory neuropathy .\ninvestigations showed anemia ( hb7.7 gm / dl ) , neutrophilic leukocytosis ( total leukocyte count 19800 cells / cmm ( n , 400011000 cells / cmm ) with 90% neutrophils .\nserum creatinine was 3.5 mg / dl ( n , 0.6 - 1.2 mg / dl ) and hba1c was 8.5%\nct abdomen revealed intraluminal and intramural gas in the bladder with thickening of bladder wall [ figure 1a c ] .\nkidneys were normal in size and shape and there was no perinephric stranding or gas in renal parenchyma or renal pelvis .\nfigure 1d shows disappearance of intramural and intraluminal gas on follow up ct imaging after 8 weeks .\nserum creatinine was decreased to 2 mg / dl , but not normalized probably because of underlying diabetic nephropathy .\n( c ) axial ct image through lower pelvis showing pneumobladder , intramural air and circumferential mural thickening .\n( d ) axial ct image through lower pelvis after treatment showing disappearance of air ; however , mural thickening is persisting\nother organisms reported include klebsiella pneumoniae , pseudomonas aeruginosa , proteus mirabilis , candida albicans , and candida tropicalis , aspergillus fumigatus , staphylococcus aureus , group d streptococcus , enterococcus faecalis , enterobacter aerogenes , and clostridium perfringens and cl .\nthe clinical presentation of emphysematous cystitis is varied ; patients can be asymptomatic , describe pnematuria , or irritative voiding symptoms , or present with an acute abdomen with severe sepsis . of reported patients with emphysematous cystitis ,\npredisposing factors for emphysematous cystitis include diabetes mellitus , neurogenic bladder , lower urinary tract obstruction , urethral catheter placement , vesicourethral reflex , and end stage renal disease .\nthe effects of diabetes mellitus on the urinary tract include diabetic nephropathy , renal papillary necrosis , renal artery stenosis , and bladder dysfunction secondary to neuropathy .\nthese factors combined with glycosuria and impaired leukocyte function place diabetic patients at greater risk of complicated utis such as emphysematous cystitis .\noverall , two - thirds of reported cases of emphysematous cystitis were diabetic and 64% were women\n. the symptoms of emphysematous cystitis are similar to those of uncomplicated cystitis , consisting of frequency , urgency , and dysuria .\ntherefore , a high index of suspicion is required for diagnosis especially in patients with risk factors .\nplain radiographs of the abdomen reveal radiolucency within the lumen of the bladder as a ring of radiolucency outlining the bladder wall .\ncomputed tomography of the abdomen is superior to plain radiographs as a diagnostic tool because it clarifies the extent and location of the gas collection as observed in our case .\na pathological assessment of involved bladder tissue might show bladder wall thickening with vesicles of varying size , and microscopically there are multiple gas filled vesicles predominantly within the bladder mucosa , lined by flattened fibrocytes and multinucleated giant cells .\nit is thought that the high glucose concentration within the tissues acts as a favourable substrate for organisms to produce carbon dioxide through facultative anaerobic glycolysis .\nhowever , this does not account for the significant number of non - diabetic patients with emphysematous infections . in such patients , urinary albumin might act as the substrate for gas production by urinary pathogens .\nanother theory suggests that an impaired host response , involving vascular compromise and impaired catabolism within the tissues , predisposes patients to gas production within these tissues . the pathogenesis is not yet fully understood , but a multifactorial aetiology of impaired host responses with sugar or protein fermentation seems to be a plausible explanation for the production of gas within the affected tissues .\nmanagement consists of adequate urinary drainage , appropriate antibiotic treatment , and good blood glucose control .\nhowever , delayed diagnosis may lead to extension to the ureters and renal parenchyma , bladder rupture , and death .\nthe gas is reabsorbed once the infection is eliminated as was seen in our patient [ figure 1d ] .\nhistory of pneumaturia and evidence of intraluminal and intramural gas along with bladder thickening on imaging clinches the diagnosis of emphysematous cystitis .", "answer": "emphysematous cystitis is a relatively rare clinical entity caused by gas - fermenting bacteria or fungus . \n presentation is often nonspecific and imaging is the best diagnostic modality . \n we report a case of a 45-year - old male who presented with fever , dysuria , and pneumaturia , and was found to have emphysematous cystitis .", "id": 608} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsoft tissue coverage for wounds remains a difficult management problem for patients sustaining traumatic injury and burns .\nthere are several methods to achieve wound coverage secondary healing , primary suturing , skin grafting , and flap surgeries as described in reconstruction ladder .\na skin graft is the most commonly used modality for coverage of wounds in reconstructive plastic surgery . the skin graft needs to undergo various stages of healing for a good take on the recipient bed .\nthere are different methods employed to secure the graft to recipient bed for a few days with a basic idea to ensure that the graft is not elevated off the bed by formation of haematoma / seroma under it .\nrepeated tie over dressings are required in situations where the dressing needs to be changed more frequently as in cases of infected raw area , bleeding tendency , patients on anticoagulant drugs , and in convex areas of body such as buttocks , breast , and the scalp , where the dressing is difficult to secure .\nin this novel method , a sterile sample container was cut at its upper part [ figures 1 and 2 ] .\nthe skin graft was applied on the raw area and fixed with skin staplers and tie over sutures . once paraffin gauze and adequate padding is applied on the raw area , the tie over threads were passed from inside out of the container [ figures 3 and 4 ] and pulled at the appropriate tension to keep the dressing in place .\nthe lid of the container was tightened to complete the dressing ensuring that the graft was maintained in close approximation with the wound surface .\nsterile plastic container upper part of the sterile container is cut tie over threads being passed from inside out the lid is tightened over the dressing the dressing can be changed repeatedly with sterile precautions depending on the requirement , as an outpatient procedure by unscrewing the lid [ figures 5 - 8 ] which can then be easily reapplied .\nthe procedure can be used on wounds of any size by changing the size of the sterile container chosen .\npost - toilet mastectomy raw area covered with the skin graft the tie over dressing applied in ot tie over dressing repeated in an outpatient department we have used this method in eight cases of the post toilet mastectomy raw areas with very good results [ figures 9 and 10 ] . post - toilet mastectomy raw area\nskin graft once applied has to be covered with petrolatum gauze to avoid its separation from the wound bed at the time of change of dressing .\nan ideal method of graft fixation should be simple , rapid , repeatable , able to be performed in the outpatient department , prevent hematoma or seroma formation , soak the exudates well , and allow the graft bed to be inspected easily .\nthere are multiple methods of securing dressings over the skin graft , some of them can be applied only once and some can be repeated .\nthe dressings that can be applied only once are like foam , hydro cellular dressing ( highly absorbent and can be easily changed ) , negative pressure therapy dressing ( stabilises the graft , increases the vascularity of bed , takes away toxic chemicals ) , and gas bag ( transparent , can see graft and monitor any haematoma ) .\nthese traditional methods can stabilize the graft till the first dressing post operatively . in some contaminated wounds ,\nthe dressing needs to be removed earlier , especially if there is drainage or foul smell .\nthis approach may also be proper for graft , used to cover defects of some anatomical regions with increases risk of contamination , such as perineal , axillary , and genital or it can be used in areas where base of wound is difficult to immobilize like breast / pectoral region .\nrepeated tie over dressings can be done by keeping interrupted sutures long to be used as tie over dressings .\nthese ties over dressing can be made of sutures or rubber bands . when taking a tie over stitch , both\nthe threads can be left long and only one thread is tied at a time , the other thread is left long for next time .\nthese techniques are difficult for small dressings especially the bra hooks ; the silk loops method is very cumbersome and takes long time to do .\nthe novel method being discussed has a very small learning curve and is very fast .\nit hardly takes 5 min in the hands of a plastic surgeon to complete the dressing .\nthis dressing technique maintains the advantage of conventional tie over dressing with rapidity and repeativity .\ngood graft take can be expected whether split - thickness or full - thickness with appropriate methods of stabilisation .\nwe recommend a novel , low cost , simple , rapid method of graft fixation that can be used repeatedly and can be applied to a wound of any size .", "answer": "tie overdressing is commonly used to secure the graft against the raw surface and prevent loss due to of hematoma or seroma . a conventional tie over dressing with silk sutures , \n is a useful method of securing the graft to raw area . \n refixation is difficult when repeated tie over dressings are needed . \n we assessed a low cost repeated tie over dressing method using sterile sample collection containers and silk suture threads in eight patients . \n after the graft is applied on the bed , tie - over stitches are taken , and paraffin gauze is applied over with adequate padding ; the tie over sutures are passed through the container and the lid is tightened over it to complete the dressing . \n the lid can be unscrewed easily at any time to inspect the graft and can be easily reapplied in the outpatient department . \n the skin graft take in all the patients was complete without any seroma or hematoma . \n a novel and low - cost tie over dressing that enables simple fixation of the dressing , to maintain proper position of grafts that require repeated fixation is reported here .", "id": 609} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSubstituent Control of s-interference Effects in the Transmission of Saturated Molecules\n\nPaper sections:\nMANUSCRIPT\nSaturated organic molecules are considered to be good molecular insulators and find widespread use in studies of electronic and magnetic communication between functional molecular units. [1][2] Destructive quantum interference in the s-system can further enable the design of saturated molecules where the electronic transmission is almost completely suppressed. [3][4][5] Destructive sinterference may appear in saturated molecules when all through-bond paths in the molecular backbone have at least one gauche defect, i.e., a dihedral angle approaching 0\u00b0. [3][4][5][6][7][8] However, full suppression of the single-molecule conductance is not often achieved and it is not always clear if the partial suppression is due to an interference effect. 5 For example, the gauche conformations of simple linear alkanes have lower conductance than the trans conformations; however, clear signatures of destructive quantum interference are missing, such as sharp antiresonance dips in the electronic transmission. [8][9][10][11][12][13][14][15][16] When s-interference effects manifest, the conductance is highly sensitive to details in the molecular geometry. Based on the extensive topological understanding of interference effects in p-systems, we expect a similar intuition should be found for s-systems. [17][18][19][20][21] However, it is an ongoing challenge to understand the structure-property relationships for the single-molecule conductance of saturated group 14 systems. 9,[22][23][24][25][26][27] We reported a surprising chemical sensitivity of the s-interference effect. 5 Despite the benign nature of the substituents, the electronic transmission of functionalized cyclohexane, cyclohexasilane, bicyclo[2.2.2]octane, and bicyclo[2.2.2]octasilane is systematically lower when the molecules are permethylated. This is exemplified in Figure 1 Substituent effects are well-established for destructive quantum interference effects in conjugated molecules. [28][29][30][31] The destructive p-interference effect can be systematically manipulated depending on the electron donating or withdrawing character of the substituent. [32][33][34][35][36][37][38][39][40] Here, we examine the substituent effect on the electronic transmission of methylthiomethyl-functionalized bicyclo[2.2.2]octane (C222), bicyclo[2.2.2]octasilane, and bicyclo[2.2.2]octagermane (Ge222).
Fully X-substituted C222-X, Si222-X, and Ge222-X structures are sampled using RDKit as described in Supporting Information part A. 41 Common to all the methylthiomethyl-functionalized bicyclo[2.2.2]-systems, the molecular core is chiral but has no conformational freedom. Therefore, the orientations of the two linkers relative to each other provide three conformations. These are shown in Figure 2 as a Newman projection along the bridgehead axis of the molecule, and as the optimized conformations of Si222-H. It is the Si-Si-CH 2 -S dihedral angles of the linkers that must be rotated to sample the three conformations. In accordance with previous work, we refer them as the anti, ortho, and cis conformers. We sample these three in all studied molecules. For a control system, we examine the equivalent linear molecule in its all-trans conformation as shown in bottom panel of Figure 2. All structures are optimized using density functional theory as implemented in Gaussian09 using the PBE exchange-correlation (XC) functional with 6-311G(d,p) basis set. [42][43] Single-molecule junctions were made by placing the optimized molecules between two four-atom Au pyramids on 5x5 Au fcc(111) surfaces. The initial junction structure is built using Au-S bond length of 2.5 \u00c5 and Au-S-C bond angle of 110\u00b0. The terminal methyl groups are rotated to a dihedral angle of \u00b190\u00b0 in order to make space for the Au atoms in the transoid position (\u00b1170\u00b0). 44 Junctions are relaxed to a force threshold of 0.06 eV/\u00c5 using DFT with the PBE XC functional and double-z plus polarization basis set as implemented in ASE and GPAW. 43,[45][46][47] Finally, the Landauer transmission is calculated using the NEGF approach as implemented in ASE. 45 We devise an extensive list of substituents based on the criterion of some extent of chemical realism, though in some cases also on chemical curiosity. The different substituents on C222-X, Si222-X, and Ge222-X are to some extent limited by the size of the molecular frame, and therefore not all substituents can be used. Scheme 1 provides an overview of all 34 molecules studied.
Optimizations of cyano-substituted Ge222-CN did not converge. It is a molecule we do not expect to be experimentally realistic, but it would have been of interest because CN is a very strong electron acceptor. Scheme 1: Overview of substituents in C222-X, Si222-X, and Ge222-X.
In the low-bias regime we study here, an insulating molecule must have strong suppression of the transmission near the Fermi energy in all its conformers. The constrained structure of the bicyclo[2.2.2]octane frame makes them shorter than the equivalent butane-motif molecules (methylthiomethyl-functionalized C4-X, Si4-X, and Ge4-X). Despite being shorter molecules (shorter tunneling barriers), previously studied the bicyclo[2.2.2]octane systems have similar or lower transmission than their linear counterparts as testament to their superior insulating properties. 3-5, 25, 48 The transmission is plotted against energy for select Si222, Ge222, and C222 molecules in 3b), however, there is some variation of the transmission depending on the conformation. The transmission of Ge222-Me is a bit higher than in the equivalent Si222-Me, and phenyl substituents may offer slightly lower conductance for germanium than methyl.
Similar suppression and variation are seen in the ethyl, vinyl, and ethynyl substituted cases of Si222 and Ge222 (Figure S3 and S4). Carbon-based substituents thus seem particularly promising for fine-tuning the insulating properties of Si222 and Ge222 systems. Although alkyl and phenyl substituents are quite benign from a chemical point of view, they are particularly promising because they are realistic synthetical targets for silicon and germanium based molecular cores. [49][50][51][52][53][54][55][56][57] We hope these results will motivate studies of the properties of substituted cyclic and bicyclic silanes and germanes. The transmission suppression is less clear in the C222 systems than for the silanes and germanes. Shown in Figure 3c, the transmission of C222-Me and C222-F does have antiresonances for some conformers. However, looking broadly at the C222 systems in Figure S2, it appears there are few cases with s-interference. We note the transmission of linear alkanes is much lower than that of linear silanes and germanes in general, 58 and the suppression effect is thus quite small in C222. For example, the suppression of the transmission in C222-H is below an order of magnitude compared to C4-H, in good agreement with experimental results. 5,48 Peralkylated bicyclo[2.2.2]octanes are not the most realistic synthetic targets, while fluorinated alkanes make for more realistic targets for single-molecule junction studies. [59][60][61] The transmissions of all C222-F conformers are suppressed over a broad energy-range compared with C4-F. Of the substituents studied for C222, fluorinated bicyclo[2.2.2]octanes are thus an interesting prospect for organic interference-based singlemolecule insulators. Generally, however, they are still not as promising as the Si and Ge based systems as only the anti-conformer has a deep antiresonance near the Fermi energy.
Certain substituents seem to promote the insulating properties of the three molecular cores. We further assess substituents based on their electron withdrawing and donating properties. Such effects have been classified in the extensive physical organic chemistry literature. 62 In Figure 4a, the transmission at the Fermi energy is plotted for all substituted molecules sorted by their oftused Hammett constants s p , which are based on the substituent effect in para-substituted benzenes. 62 Except for F and Cl, the substituent effect is fairly similar across the C222, Si222, and Ge222 series. However, there is no clear correlation across the full transmission data set when plotted against s p . Motivated by the strong transmission suppression seen for many of the carbon-based substituents, we separate the data set into two types of substituents: those based on carbon (blue in Figure 4a) and the remaining that are not carbon based (red in Figure 4a). We search further for quantitative correlations in substituent parameters that are determined in systems with suppressed or separated p-conjugation. 62 In addition to s p , we plot the transmission values against the Hammett constant, s m , which are determined on meta-substituted benzenes and the inductive parameter F.
While all these parameters are determined empirically, F may provide a better measure of the substituent effect on the s-system as it uses a bicyclo[2.2.2]octane compound for reference. 62 Shown in Figure 4b, the transmission of the three cores with carbon-based substituents is plotted against the three different Hammett constants. While there is a weak correlation for C222, both Si222 and Ge222 transmission show strong correlation with all three empirical parameters. These correlations are consistently weaker for the non-carbon substituents as plotted in Figure 4c. There is some correlation for these substituents in the Ge222 with s m and F, but in the remaining systems there is no correlation between the transmission and the Hammett constants.
The carbon-based substituents (listed in blue in Figure 4a) stand out from their non-carbon counterparts. They enable the lowest transmission for the Si222 and Ge222 systems, and their transmission correlates with the electron withdrawing properties of the substituents as given by the empirical Hammett constants. These correlations are quite strong compared to the correlations reported in other single-molecule conductance studies. [63][64][65] Carbon-based substituents thus provide an opportunity for fine-tuning s-interference effects in silicon and germaniumbased compounds.
The carbon-based substituents we find here appear to be special for the silicon-and germaniumbased cores, but do not systematically promote interference effects in the carbon-based core. As previous studies have suggested, the s-interference effect is highly sensitive to several structural and electronic parameters. [3][4][5][6][7]24 We have tested for correlations with structural parameters in our dataset but have not found any clear correlation, see Supporting Information part B for details. This indicates the effect of substituents is electronic (donor/acceptor effect) rather than from the distortion of the structure in molecular core. While these two effects (electronic and structural) are not independent of each other, the clear correlation we see for the carbon-based substituents with the Hammett constants suggests the effect is primarily electronic. Most likely, carbon-based substituents are special because they tune the electronic structure within an ideal range where there is s-interference in the transmission. This balance of parameters that enables interference effects in saturated molecules is still not well-described, but clearly the s-interference effect is very sensitive to both chemical and structural changes.
To summarize, a wide range of substituents can result in significant destructive interference effects in the transmission of Si and Ge cores. These are substituents based on carbon, such as alkyl and phenyl substituents, and we show that this substituent effect is systematic by correlating the transmission with different Hammett constants. However, we find that fluorination appears to be the only substituent that is likely to result in significant conductance-suppression in the carbonbased bicyclo[2.2.2]octane we have studied here. s-interference thus appears to be much more sensitive to chemical changes than the more well-established p-interference effect. Until recently, we may have thought that saturated molecules are some of the simplest and best understood systems in molecular electronics. Recent results by us and other groups suggest there is much more potential, 5, 66 which may be applied for novel chemical designs. This letter is a step in this direction, and future work must continue to build on the electron transport structure-property relationship of saturated carbon molecules and their heavier group 14 analogues.
", "answer": "The single-molecule conductance of saturated molecules can potentially be fully suppressed by destructive quantum interference in their s-system. However, only few molecules with s-interference have been identified and the structure-property relationship remains to be elucidated. Here, we explore the role of substituents in modulating the electronic transmission of saturated molecules. In functionalized bicyclo[2.2.2]octanes, the transmission is suppressed by sinterference when fluorine substituents are applied. For bicyclo[2.2.2]octasilane andoctagermanes the transmission is suppressed when carbon-based substituents are used, and such molecules are likely to be highly insulating. For the carbon-based substituents we find a strong correlation between the appropriate Hammett constants and the transmission. The substituent effect enables systematic optimization of the insulating properties of saturated molecular cores.", "id": 610} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nFacile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction\n\nPaper sections:\nIntroduction\nThe spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5]. The unique structures and the highly pronounced pharmacological activity displayed by the spirooxindoles have made them attractive synthetic targets [6][7][8][9]. In various heterocyclic and carbocyclic spirooxindoles, the spiro-oxirane-oxindoles are a particular class of compounds with both spiro-carbon and unstable oxirane features in the molecule. These fascinating spiranic frameworks can serve as important building blocks in organic synthesis for the synthesis of large-ring heterocycles [10][11][12][13]. As a consequence, in recent years much attention has been paid to the diastereoselective and enantioselective synthesis of versatile spiro-oxirane-oxindoles [14][15][16][17][18][19]. With the aim of expanding our previous studies on the synthesis of various spirooxindoles [20][21][22][23][24][25], we decided to systematically investigate the Darzens reactions of a series of isatins with phenacyl bromides and report the facile synthesis of versatile spiro[indoline-3,2'oxiran]-2-ones.
\n\nResults and Discussion\nIn recent years we have found that pyridinium salts react with versatile reactive methylene compounds to give different kinds of products, including functionalized cyclopropanes, 2,3-dihydrofurans, polysubstituted pyridines, pyrido[1,2-a]benzimida-Scheme 1: Synthesis of spiro-epoxyoxindole with pyridinium ylide. zoles and charge-separated zwitterionic salts [26][27][28][29][30][31]. We envisaged that in situ generated pyridinium ylide might react with the reactive carbonyl group of isatins to afford spiro epoxyoxindoles (Scheme 1). To test this feasibility, the reactions of various substituted isatins with pyridinium salt in the presence of base were examined under different conditions. We were disappointed that the reactions produced much complicated mixtures and no acceptable results were obtained. Thus, our attention was turned toward the development of straightforward reactions of phenacyl bromides with isatins.
In a preliminary experiment, a model between 5-methylisatin (1) and phenacyl bromide (2) was examined under a broad set of conditions (Table 1). A careful screening of bases revealed that potassium afforded the product in better yields. The main problem is that the N-alkylated spiro epoxyoxindole 4 is accompanied by the formation of spiro epoxyoxindole 3 even if equivalent reactants are used, which is consistent with the recently reported reactions of isatins with alkylating agents having an acidic methylene group by Blanco et al. [19]. To our delight, the spiro epoxyoxindole 3 could be selectively obtained in 85% yield when the reaction was carried out in the system of K 2 CO 3 /CHCl 3 at about 50 \u00b0C for 10 h. On the other hand the N-alkylated spiro epoxyoxindole 4 was also successfully prepared in 90% yield in this system when more than two equivalents of phenacyl bromide were utilized. After obtaining the optimized reaction conditions, various substituted isatins and phenacyl bromides were employed in the reaction. The results are summarized in Table 2. All reactions proceeded very smoothly and eight spiro epoxyoxindoles 3a-h were obtained in satisfactory yields. Similarly the N-substituted spiro epoxyoxindoles 4a-e were synthesized in high yields by using an excess of phenacyl bromide. The results are summarized in Table 3. The structures of compounds 3a-h and 4a-e were characterized by IR, 1 H, 13 C NMR, and HRMS spectra and were further confirmed by single-crystal X-ray diffraction determination of the compound 3c (Figure 1) and 4a (Figure 2).
It should be pointed out that some of the spiro epoxyoxindoles 3a-h have been previously prepared by other methods and the related references are also listed in Table 2. The 1 H NMR spectra of compounds 3a-h and 4a-e usually show one set of characteristic peaks for each group, especially one singlet at about 5.10 ppm for one proton of the epoxy unit, which clearly indicates that only one isomer exists in each sample. However, 1 H NMR spectra of compounds 3a and 3f clearly displayed that the trans-isomer existed mainly with ratios of cis/trans isomers of 1:14 and 1:8, respectively. From Figure 1 and Figure 2 it is seen that the phenyl group of the oxindole unit and the benzoyl group existed in the cis-position. This result also indicated that the thermodynamic reaction produces a more stable transisomer.
To further illustrate the power of this reaction procedure, the N-substituted isatins were also employed to react with phenacyl bromides under similar reaction conditions. A series of new spiro epoxyoxindoles 5a-p were prepared in high yields (Table 4). The structures of the spiro compounds 5a-p were also established by spectroscopic methods and were confirmed by single-crystal X-ray structure determination of compound 5o (Figure 3). 1 H NMR spectra showed that a mixture of cis/trans isomers existed in most samples with a large range of different cis/trans ratios. It is known that the closure of the epoxy ring would form cis/trans isomers in the Darzens reaction process.
Here the N-benzyl and the N-butyl group in the oxindole moiety may decrease the steric effect of formation of the epoxy ring and lead to the easier formation of the relatively unstable cisisomer.
\n\nConclusion\nIn summary, we have systematically investigated the Darzens reaction of phenacyl bromides with isatins for the efficient synthesis of the functionalized spiro epoxyoxindoles. Both the nonsubstituted isatins and N-alkylated isatins were successfully used in the reactions. The scope and limitation of the reaction was established. The N-alkylation of the isatins is usually accompanied by the formation of spiro epoxyoxindoles.
\n\nExperimental\nReagents and apparatus: Melting points were taken on a hotplate microscope apparatus. IR spectra were obtained on a Bruker Tensor 27 spectrometer (KBr disc). NMR spectra were recorded with a Bruker AV-600 spectrometer with DMSO-d 6 as solvent and TMS as internal standard (600 and 150 MHz for 1 H and 13 C NMR spectra, respectively). HRMS were measured on a UHR-TOF maXis instrument. X-ray data were collected on a Bruker Smart APEX-2 diffractometer. Isatins, phenacyl bromide and other reagents are commercial reagents and were used as received. Solvents were purified by standard techniques. All reactions were monitored by TLC.
\n\nTypical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 3a-h:\nA mixture of isatin (1.0 mmol), phenacyl bromide (1.0 mmol) and potassium carbonate (1.2 mmol) in 20.0 mL chloroform was stirred at 50 \u00b0C for 10-24 h (TLC analysis). After cooling the reaction was quenched with water. The solvent was evaporated under reduced pressure. The residue was recrystallized from ethanol to give the pure product for analysis.
\n\n3'-benzoylspiro[indoline-3,2'\n-oxiran]-2-one (3a) [32] Typical procedure for the preparation of spiro[indoline-3,2'-oxiran]-2-ones 5a-p: A mixture of isatin (1.0 mmol), phenacyl bromide (1.2 mmol) and potassium carbonate (1.5 mmol) in 20.0 mL of chloroform was stirred at 50 \u00b0C for 10-24 h (TLC analysis). After cooling, the reaction was quenched with water. The solvent was evaporated under reduced pressure. The residue was recrystallized with ethanol to give the pure product for analysis.
3'-benzoyl-1-benzylspiro[indoline-3,2'-oxiran]-2-one (5a) [35]
", "answer": "A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N-alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles.", "id": 611} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe treatment of chronic hepatitis c ( chc ) has evolved in the last 15 years from monotherapy with interferon alpha ( ifnalpha ) to the combination treatment with pegylated ifn ( peg - ifn ) plus ribavirin for 24 - 48 weeks . up to now , several viral , host and drug - related reactions in response to ifnalpha - based therapy have been identified .\nrecent studies suggest that liver inflammation in chc is controlled by several mechanisms , including host regulatory immune responses and viral polypeptides interacting with cells involved in innate and adaptive immunity .\nit is well known that cutaneous side effects of treatment with ifnalpha alone or ifnalpha plus ribavirin in patients with chc have been widely reported , beyond the fact that the virus itself can cause skin lesions . however , the cutaneous side effects during therapy of chc are of inflammatory type with local erythema , edema and , much less frequently , necrosis at the injection skin sites . by contrast ,\nskin side effects of such drugs have few data available in the literature , although the number of reports has been increasing in the last years , including cosmetic filler site injections .\nroughly one half of these patients had cutaneous findings , either alone or with systemic involvement .\nmore recently there have been reported dermatological diseases in patients receiving the combination of ifn / ribavirin or ifn / ribavirin / amantadine for the treatment of chc .\na 44-year - old man with chc genotype 1a and a viral load of hcv > 800,000 iu / ml , a2-f1 on liver biopsy according to metavir criteria , was treated for the hepatic disease .\npeg - ifnalpha-2b 1.5 g / kg weekly and 1,000 mg of ribavirin daily was introduced . in the 40th week\nthe patient reported sudden intense pain , pruritus , erythema and skin hypertrophy in the left deltoid area over the seahorse tattoo and in a scar on his face ( fig .\n1 ) . a skin biopsy on the scar and tattoo showed granulomatous dermatitis ( fig .\nchest x - ray was normal and the level of angiotensin enzyme converter was 50 iu / ml ( range 18 - 55 iu / ml ) .\nwe intend to call attention especially to dermatologists to the possibility of a granulomatous tattoo reaction as a side effect during chc treatment with peg - ifnalpha-2b plus ribavirin . until now\n, eight cases of sarcoidosis as a complication of ifn therapy in chc have been reported in the english language literature .\nthe most relevant topic in this case is the occurrence of disease on a tattoo area .\nsix months later retreatment using peg - ifnalpha-2a 180 g once a week plus ribavirin 1,000 mg daily was tried . in the 6th week , cutaneous symptoms relapsed in an unbearable way .\nthe patient did not accept to continue therapy , since hydrocortisone cream was prescribed again but no satisfactory pruritus and pain improvement was noticed . a prompt regression of skin reaction occurred after stopping therapy .\nsarcoidosis is a granulomatous disorder of unknown etiology and whose epidemiology suggest a genetic tendency face to infectious agents being supposed to result of immune system deregulation leading to non - caseating granulomas as an immune reaction to an unknown persistent antigenic stimulus .\nifn has been linked to pulmonary macrophage activation , a characteristic feature of sarcoidosis which has been assumed an exaggerated t helper 1 ( th-1 ) immune response to a variety of exogenous antigens .\nit seems very likely that a potent immunoregulatory protein for th-1 response such as ifn may induce the disease . in january 2003 the eighth case of ifn - related sarcoidosis was reported with a review of the literature .\nchest x - ray revealed hilar lymphadenopathy in three patients , with reticulonodular shadows in another three , while the patient with only cutaneous involvement had a normal chest x - ray .\nthe case we report presented with cutaneous sarcoidosis during chc therapy and spontaneous regression of the lesions was noted with treatment discontinuation .\nwe intend to emphasize , especially to dermatologists , the risks of a granulomatous tattoo and other cutaneous sites during chc treatment with peg - ifnalpha-2b plus ribavirin .\nthalidomide has been also shown to have specific activity to the inflammatory mediators of sarcoidosis and to be an alternative beneficial therapy .", "answer": "the treatment of chronic hepatitis c ( chc ) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy . however , several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment . \n although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances , some cases have been reported even with conventional interferon . \n this brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient 's face , during treatment with pegylated interferon alpha-2b plus ribavirin , is an educative report directed in special to dermatologists . \n the lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a . \n we conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances . \n no differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment .", "id": 612} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngeriatric population is on rise globally because of increasing life span . as per the us census ,\npeople above 60 years constituted 6.4% of the total population in 1900 , which increased to 18.4% in 2010 and predicted to go up to 25.5% by 2050.1 spinal problems and spine surgeries in geriatric population are also showing a similar trend .\nlumbar fusion surgeries in people aged 60 years and above have increased by 230% in a decade from 1991 to 2001.2 desire to lead a more active life in advanced age , improved diagnostic techniques , and better operative results are some of the reasons for increasing spine surgeries in the elderly . in general , spine surgery in the elderly in the presence of comorbidities\nis feared among both patients and surgeon , as it is presumed to have higher perioperative complications and increased cost .\nmany articles can be found in literature supporting this.345 a study by daubs et al .\ninvolving adult spinal deformity in people over 60 years of age has reported that age and complication rates do not affect the surgical outcome.6 similar studies have reported 91%96% good to excellent results following surgical treatment of lumbar canal stenosis ( lcs ) by decompression and decompression with fusion on people aged above 6570 years.789 this indicates that in the absence of complications , spinal decompression and fusion surgeries would result in a satisfied patient even in the elderly with comorbidities .\ntherefore , measures to reduced complications in such patients should be looked at rather than denying surgical management in symptomatic patients due to their old age or comorbidities .\nthis study evaluates the perioperative complications and the contributing factors in patients over 60 years of age undergoing lumbar fusion surgeries .\npatients aged 60 years and above with one or more comorbidities undergoing lumbar decompression and instrumented fusion at our institute between january 2012 and december 2013 ( 2-year period ) were included in the study . in all these patients ,\nperioperative complications ( intraoperative and complications occurring within 3 weeks postoperative period ) and their incidence were recorded .\nthe technique was a standard open technique of pedicle screw instrumentation and fusion , either interbody by transforaminal approach or posterolateral using morcellized bone from the posterior elements or rarely with iliac crest .\nage , number of levels instrumented and fused , operative time , blood loss , comorbidities , and the duration of stay were correlated with the incidence of perioperative complications using spss software ( ibm , spss statistics v 23.0 , new york , united states ) .\nfactors contributing to perioperative complications were noted and measures to reduce them were suggested by these results and compared with the available literature in discussion .\nanalysis of our medical records revealed a total of 52 patients operated by lumbar fusions in the 2-year study period , who were aged 60 years and above and had one or more comorbidities .\nmost common indication for surgery was spondylolisthesis in 17 ( 32.7% ) followed by lcs in 15 ( 28.8% ) patients .\nhypertension ( htn ) was the most common comorbidity found in 39 patients ( 75% ) , followed by diabetes mellitus ( type 2 ) in thirty patients ( 56.4% ) .\ntwenty patients had single comorbidity while 18 patients had two comorbidities and 13 patients were found to have three comorbidities [ table 1 ] .\npreoperative mri t2w , midsagittal ( a ) and axial ( b ) images showing multilevel listhesis and canal stenosis .\npostoperative x - ray lumbosacral spine anteroposterior ( c ) and lateral ( d ) views showing implant ( pedicle screws ) in situ following instrumented fusion diagnosis and comorbidites of patients forty six patients were operated under general anesthesia ( ga ) while the remaining six patients were operated in regional or spinal anesthesia .\n3.8 levels were the average levels instrumented per patient while one patient underwent 9 levels instrumentation .\ninterbody fusions were performed at single level in 24 , 2 levels in 22 , and 3 levels in 6 patients .\naverage operative time and blood loss were 150 min ( range 60270 min ) and 369 ml ( range 901050 ml ) , respectively . both operative time and blood loss\nthe levels of instrumentation and fusions were decided on segmental instability observed on dynamic radiographs .\nthe interbody fusions were based on degree of segmental stenosis , disc degeneration , and instability .\nclinical details of patients operative time and blood loss with respect to the number of interbody fusion levels a total of 11 complications were noted , 3 systemic and 8 local . among the systemic complications , 2 were hypostatic pneumonia with secondary infection and one was a psychiatric illness called ganser 's syndrome . all the three patients required transfer to icu and one patient with pneumonia expired due to septicemia and shock .\nthe average total duration of stay in the hospital was 6.2 days ( range 4 - 14 days ) .\non comparing the complication rates with other variables , we found that the patients with complications had higher blood loss , operative time , number of instrumented levels , and number of interbody fusion levels [ tables 4 and 5 ] .\nsimilarly , the duration of stay was longer in these patients . on analyzing these results statistically by anova , the association of blood loss with complications was found to be statistically significant with p = 0.002 .\nthe duration of stay , operative time , and number of interbody fusion levels were close to significance with p = 0.63 , 0.58 , and 0.61 , respectively , while number instrumented levels and the number of associated comorbidities showed no significance [ tables 4 and 5 ] .\nthe complications and their incidence comparisons of different variables in patients with and without complications on analyzing the correlations between different variables , we found that there was a strong positive correlation of blood loss with operative time , number of instrumented levels , and number of interbody fusions which was statistically significant .\nsimilarly , operative time showed a strong positive correlation with number of interbody fusions and a significant but a weaker positive correlation with number of instrumented levels [ table 6 ] .\nthe perioperative complication rates in the present study occurred in 11 of 52 patients with an incidence of 21% . increased blood loss strongly correlated with the incidence of complications .\nage , operative time , number of levels of fusion , and the duration of stay were also more in patients with complications and were close to statistical significance while number of instrumented levels and number of associated comorbidities were unrelated to the complication rates .\nperioperative complication rates in instrumented lumbar fusions in patients above 60 years of age described in literature range from 29% to 62% [ table 7 ] .\nreported increased complications in patients with advanced age and surgeries with increased blood loss and number of levels of fusions.1112 carreon et al.11 found increased complication rates with increased operative time while cho et al.12 found no such association .\nguigui et al.10 found comorbidities to influence the complication rates and a similar study by acosta et al.4 found ten times higher complication rates in patients with htn while others found no association between comorbidities and the perioperative complications.612 the incidence of complications and factors affecting it described in the literature considering the group of population included , the complication rate in our series was within the acceptable limits compared to literature [ table 7].4611121314 our patients were 60 years and above with the average age of 69 years , all of them had one or more comorbidities , and the average number of levels fused was 3.8 , making this group more vulnerable for complications . despite this , the complications in our series were about 21% with most of them being minor reversible complications such as dural tear , transient root deficits , and postoperative persistent radicular pain .\nsimilarly , the operative time and blood loss , in our series , was lesser compared to that described in literature for multilevel fusions [ table 7].4611121314 the blood loss in literature ranged from 206 ml in single level to 2056 ml in 9-level fusions and the operative time ranged from 145 min in single level to 415 min in 10.5-level fusions [ table 7].4611121314 in comparison in our series with an average of 3.8 levels of fusion , the average operative time and blood loss were 150 min ( range 60270 min ) and 367.45 ml ( range 901050 ml ) , respectively .\nthis could possibly explain the lesser complication rates in our study as the complications were strongly related to the operative time and blood loss .\non reviewing literature and analyzing our surgical technique , we found several strategies that helped in reducing the blood loss and operative time , and hence the complications .\ninjection tranexamic acid 1 g intravenous was given routinely preoperatively , immediately before skin incision in all cases .\nliterature describes that a single dose of tranexamic acid 15 mg / kg can effectively reduce blood loss without increasing the risk of deep vein thrombosis.15 the other technique employed in our surgeries was simultaneous exposure and instrumentation on either side by two trained spine surgeons [ figure 2 ] .\nthis reduced the surgery time and also the blood loss as compared to a single surgeon exposing and instrumenting one side after the other .\nwe employed a laminectomy technique described by okuda et al.16 in which lamina was removed as a single fragment using osteotome and making cuts at pars on either side .\nthis further reduced the operative time as compared to the classical technique of removing the lamina piecemeal by rongeurs .\n( a and b ) intraoperative images showing the technique of bilateral exposure and bilateral instrumentation operative time and blood loss were strongly related to the number of levels of vertebra instrumented and fused . even though operative time and blood loss could be reduced by reducing the number of instrumented and fused levels , not instrumenting or fusing the levels when indicated would compromise the principles of surgery and therefore affect the clinical outcome .\nhence , the number of vertebrae fused or instrumented should be restricted to the minimum indicated levels , without compromising on indications .\nwe also found that the blood loss increased steeply with number of interbody fusion levels .\nthe average blood loss in single level interbody fusion was 307 ml which increased to 362 ml in 2 levels and almost doubled in 3-level interbody fusions [ table 3 ] .\nthe reason for this exponential increase being continued bleeding from the bed of prepared interbody levels while performing the next level .\nperforming interbody fusions at selected levels such as the most stenotic or unstable levels or at the bottom of the construct and posterolateral fusions at other levels also could reduce the blood loss and hence the complications [ figures 3 and 4 ] . bar diagram showing the relation between the intraoperative blood loss and number of interbody fusion levels postoperative x - rays anteroposterior and lateral views of lumbosacral spine showing interbody fusions at l2l3 , l4l5 , l5s1 with posterolateral fusion at l3l4 images apart from reduction in operative time and blood loss , a thorough preoperative workup with concerned specialist consultations such as pulmonologist , cardiologist , and optimization of the medical conditions helped in reducing the anesthetic risks during surgery .\nsix of our patients in the series underwent surgery under spinal or combined spinal epidural anesthesia , due to poor pulmonary or cardiac status .\nstudies have shown regional anesthesia ( ra ) in spine surgery to have many advantages over ga in high - risk patients , like lesser anesthetic intraoperative complications , lesser postoperative htn , respiratory and cardiovascular complications , lesser postoperative vomiting , longer postoperative analgesia , and shorter hospital stay.1718 as surgeons we found spinal anesthesia to be satisfactory with reduced blood loss due to stable blood pressure one of these patients underwent surgery in sitting position which has shown in literature to be more convenient for the patient under ra , with the blood draining by gravity , resulting in clearer operative field and also reduce anesthesia complications by creating a hemodynamic status similar to that in othostasis.19 early mobilization postoperatively with optimal control of medical comorbidities also helped in reducing the early postoperative complications .\nlumbar fusion surgeries in the elderly with comorbidities have higher complications rates . increased intraoperative blood loss significantly correlated with the complication rates .\nspinal decompression and fusion surgery when indicated should not be denied merely considering the age and comorbidities of the patients , fearing complications .\ncauses and measures to reduce complications should be considered as the outcome of surgeries in these patients in the absence of complications is good .\nthe authors propose some of the measures to reduce the operative time , blood loss , and hence the complication rates in these patients . \n\nmahesh - research grant by ulrich india and consultancy from medtronic india ltd.upendra - research grant from medtronic india . \n \n\n mahesh - research grant by ulrich india and consultancy from medtronic india ltd.upendra - research grant from medtronic india .", "answer": "background : spine surgery in elderly with comorbidities is reported to have higher complication rates and increased cost . however , the surgical outcome is good irrespective of the complications . \n hence , it is essential to identify the factors affecting the complication rates in such patients and the measures to reduce them . \n this retrospective observational study determines the perioperative complications , their incidence and the measures to reduce complications in the elderly with comorbidities , operated by instrumented multilevel lumbar fusion.materials and methods : patients aged 60 years and above with one or more comorbidities operated by multilevel instrumented lumbar fusion in our center between january 2012 and december 2013 were included in the study . \n perioperative complications and their incidence were calculated . \n age , number of levels fused , operative time , blood loss , and complication rates were correlated with the duration of stay and the incidence of perioperative complications using spss software . measures to reduce complications \n are determined by these results and by review of literature.results:fifty two patients were included in the study ( 28 females and 24 males ) with an average age of 69 years ( range 60 - 84 years ) . \n hypertension was the most common comorbidity followed by diabetes . \n spondylolisthesis was the most common indication . \n eleven complications were noted with an incidence of 21% . \n three were systemic complications which required transfer to intensive care unit . \n local complications were incidental durotomy ( three ) , transient root deficits ( two ) , wound infections ( one ) , and persistent radicular pain ( two ) . \n operative time and blood loss were significantly higher in patients with complications.conclusion:complication rates strongly correlate with the blood loss and operative time . reducing the operative time and blood loss by intraoperative tranexamic acid , laminectomy using osteotome , simultaneous bilateral exposure and instrumentation and reducing the number of interbody fusions can help in reducing the complications .", "id": 613} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nReactivity of bromoselenophenes in palladium-catalyzed direct arylations\n\nPaper sections:\nIntroduction\n(Hetero)aryl-substituted selenophenes represent a class of molecules which exhibit useful physical properties, especially for the preparation of artificial photosynthetic systems for solar energy conversion or for thin film transistor applications [1][2][3]. In most cases, these (hetero)arylated selenophenes are currently prepared through the use of transition-metal-mediated reactions such as Stille [3][4][5][6][7][8][9], Suzuki [10][11][12][13][14][15][16][17][18][19], or Kumada [20] couplings [21] (Scheme 1a and b). However, all these procedures require the preparation of an organometallic or a boron derivative of one of the coupling partners, and provide an organometallic salt (MX) as waste. In recent years, the Pd-catalyzed arylation, via a C-H bond activation, of a broad range of heteroaromatics using aryl halides as reaction partners was demonstrated to be particularly effective for the preparation of bi(hetero)aryls [22][23][24][25][26][27][28][29][30][31]. Among the reported results, a few examples of Pd-catalyzed direct arylations via the C-H bond activation of selenophenes using aryl halides as coupling partners have been reported [32][33][34][35]. Conversely, C-H bond activation methodology was employed in only in one case for the preparation of a heteroarylated selenophene from a haloselenophene. Wipf et al. reported in 2014 that using ethyl oxazole-4-carboxylate as reaction partner, the corresponding 2,5-bis(oxazol-2-yl)selenophene derivative was formed in 45% yield (Scheme 1c) [17]. Moreover, to our knowledge the Pd-catalyzed direct heteroarylation of 2-bromoselenophene has not yet been described. Therefore, the reactivity of 2-bromo-and 2,5-dibromoselenophenes in Pd-catalyzed direct couplings with heteroarenes needed to be investigated.
Herein, we wish to report on the reactivity of 2-bromoselenophene, 2,5-dibromoselenophene and 2-aryl-5-bromoselenophenes in palladium-catalyzed direct heteroarylations with a variety of heteroarenes using a phosphine-free palladium catalyst.
\n\nResults and Discussion\nFirst, we examined the influence of the reaction temperature, using DMA as solvent, KOAc as base and 2 mol % Pd(OAc) 2 as catalyst (Table 1). We had previously observed that these reaction conditions allowed the coupling of several heteroaro-matics such as thiazole, pyrrole, furan or imidazole derivatives with aryl bromides [36]. 2-Bromoselenophene, which was easily prepared by reaction of selenophene with N-bromosuccinimide [37], and 2-ethyl-4-methylthiazole were employed as model substrates for our study. Reactions performed at 130 \u00b0C or 110 \u00b0C gave the expected arylated selenophene 1 in 55% and 64% yields, respectively, with complete conversions of 2-bromoselenophene; whereas 1 was obtained in a higher yield of 80% when the reaction was conducted at 90 \u00b0C (Table 1, entries 1-3). At elevated temperature (110-130 \u00b0C), 2-bromoselenophene seems to afford larger amounts of selenophene oligomers as side-products. The use of PdCl 2 or PdCl(C 3 H 5 )(dppb) as catalysts instead of Pd(OAc) 2 or other bases such as K 2 CO 3 , Cs 2 CO 3 , CsOAc or NaOAc afforded 1 in lower yields (Table 1, entries 4-9). The influence of two other solvents in this cross-coupling reaction was also examined. We observed that both DMF and xylene in the presence of 2 mol % Pd(OAc) 2 catalyst with KOAc gave 1 in moderate yields (Table 1, entries 10 and 11). Then, we investigated the scope of the coupling of 2-bromoselenophene with a set of heteroarenes in the presence of 2 mol % Pd(OAc) 2 , KOAc as the base in DMA at 90 \u00b0C (Scheme 2). The reaction of 2-isopropyl-4-methylthiazole gave the desired product 2 in 82% yield. Conversely, low yields in the target products 3-5 were obtained for the reactions with thiophene-2-carbonitrile, 2-chlorothiophene and 2-pentylthiophene, although complete conversions of 2-bromoselenophene were observed. A similar result was obtained for the reaction with 1-phenylpyrrole. Reactions performed at a higher temperature with thiophene-2-carbonitrile, 2-chlorothiophene afforded 3 and 4 in slightly lower yields. Gorelsky calculated that the Gibbs free energies of activation for the cleavage of C-H bonds at C5-position of thiophene or pyrrole derivatives, for reaction which proceed via concerted metallation-deprotonation [38][39][40], are higher than that of thiazoles (see bottom of Scheme 2) [42]. We assume that, due to these higher energies of activation for reactions with thiophene or pyrrole, larger amounts of selenophene oligomers were formed in the presence of these less reactive heteroarenes. Then, the reactivity of imidazo[1,2a]pyridine, which contains a very reactive C-H bond at C3-position was examined. The expected product 7 was obtained in a high yield of 81%. Thus, for Pd-catalyzed direct heteroarylations of 2-bromoselenophene, only the heteroarenes containing C-H bonds with low Gibbs free energies of activation [41] should be employed.
By contrast, the direct arylation reactions with 2,5-dibromoselenophene were found to tolerate both thiazole and thiophene derivatives (Scheme 3). The coupling of 3 equiv of thiazole derivatives with 2,5-dibromoselenophene in the presence of 2 mol % Pd(OAc) 2 and KOAc as base gave the corresponding 2,5-diheteroarylated selenophenes 8 and 9 in 78% and 80% yields, respectively. The use of 2-pentyl-and 2-chlorothiophenes also gave the desired products 10 and 11 in high yields. In general, the Pd-catalyzed direct arylation of 3-substituted thiophenes with aryl halides afforded quite regioselectively the C2-arylated thiophenes [30]. A similar regioselectivity was oberved for the coupling of thiophene derivatives containing methyl-or chloro-substituents at the C3-position with 2,5dibromoselenophene. In both cases, regioselective arylations at the C2-positions were observed, affording the 2,5-diarylated selenophenes 12 and 13 in 69% and 72% yields, respectively. From 2,5-dibromoselenophene and an excess of 1-methylpyrrole, the expected 2,5-diarylated selenophene 14 was obtained in 81% yield. Finally, we show a sequential transformation leading to 2-aryl-5-(heteroaryl)selenophenes in three steps from commercially available compounds (Scheme 4). Bromination at the C5-position of 2-arylselenophenes containing nitrile, acetyl or chloro substituents on the aryl moiety, could be easily obtained in good yields from selenophene and aryl bromides via a Pd-catalyzed direct arylation using a reported procedure [33], afforded the 2-aryl-5-bromoselenophenes 15-17 in 84-90% yields. Then, a second Pd-catalyzed direct arylation using heteroarenes and 15-17 as reaction partners, provided the target compounds 18-26 in high yields. Both thiazole and thiophene derivatives were successfully employed in this transformation. The reaction tolerates useful functional groups on both coupling partners such as nitrile, acetyl or chloro. It should be mentioned that again a regioselective arylation at the C2-position of 3-chlorothiophene was observed affording 26 in 72% yield.
Although the mechanism of these reactions was not elucidated, the catalytic cycle shown on Scheme 5 can be proposed. The first step is probably the oxidative addition of the 2-bromoselenophene to Pd(0) to afford the Pd(II) intermediate A.
Then, after elimination of KBr with KOAc, a concerted metalation-deprotonation pathway involving an heteroarene gives B. Reductive elimination affords the 2-heteroarylated selenophene with regeneration of the Pd(0) species.
\n\nConclusion\nIn summary, the reactivity of 2-bromoselenophenes was investigated and revealed that the C2-heteroarylation of 2-bromoselenophene in high yields is only possible with specific heteroarenes such as thiazoles and imidazopyridines, whereas thiophene or pyrroles gave the desired products in low yields. Conversely, 2,5-dibromoselenophene was successfully coupled with both thiazoles and thiophenes in the presence of phosphine-free Pd(OAc) 2 catalyst precursor and KOAc as inexpensive base, affording the desired 2,5-diheteroarylated selenophenes in high yields. We also described that the sequential catalytic C2-arylation, bromination, and catalytic C5-arylation of selenophene provides the controled double (hetero)arylation at the C2 and C5 positions of selenophene in good yields.
\n\nExperimental\nGeneral procedure for palladium-catalyzed direct mono-heteroarylations of 2-bromoselenophene
The reaction of the heteroarene (1.5 mmol), 2-bromoselenophene (0.210 g, 1 mmol) and KOAc (0.196 g, 2 mmol) at 90 \u00b0C during 24 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 1-7 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 3 and 4. EtOAc/pentane 2:98 for compounds 1 and 6. EtOAc/pentane 10:90 for compound 2 and 5 and EtOAc/pentane 40:60 for compound 7.
\n\nGeneral procedure for palladium-catalyzed direct diheteroarylations\nThe reaction of the heteroarene (3 mmol), 2,5-dibromoselenophene (0.289 g, 1 mmol) and KOAc (0.392 g, 4 mmol) at 90 \u00b0C during 40 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 8-14 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 10-13. EtOAc/ pentane 5:95 for compounds 8, 9 and 14.
\n\nGeneral procedure for the synthesis of 5-bromo-2-arylselenophenes 15-17\nTo a mixture of the 2-arylselenophene [2] (2 mmol) in DMF (5 mL) at 0 \u00b0C, N-bromosuccinimide (0.392 g, 2.2 mmol) was slowly added. Then, the mixture was allowed to increase to room temperature and stirred during 20 h. After addition of water, the extraction was carried out with diethyl ether. Then, the organic phase was dried over magnesium sulphate. Finally, evaporation of the solvent and purification on silica gel afforded the 5-bromo-2-arylselenophenes 15-17. Eluents: Pentane for compounds 15 and 16. EtOAc:pentane 5:95 for compound 17.
\n\nGeneral procedure for palladium-catalyzed direct mono-heteroarylations of 2-bromo-5arylselenophenes\nThe reaction of the heteroarene (1.2 mmol), 2-bromo-5-arylselenophene 15-17 (1 mmol) and KOAc (0.392 g, 4 mmol) at 150 \u00b0C during 16 h in DMA (4 mL) in the presence of Pd(OAc) 2 (4.5 mg, 0.02 mmol), under argon affords the coupling products 18-26 after evaporation of the solvent and purification on silica gel. Eluents: Pentane for compounds 21 and 22. EtOAc/pentane 5:95 for compounds 18 and 19. EtOAc/pentane 10:90 for compounds 20, 23, 24 and 26. EtOAc/pentane 20:80 for compound 25.
\n\nORCID \u00ae iDs\nRidha Ben Salem -https://orcid.org/0000-0002-5179-351X Jean-Fran\u00e7ois Soul\u00e9 -https://orcid.org/0000-0002-6593-1995 Henri Doucet -https://orcid.org/0000-0002-1410-3663
", "answer": "The reactivity of 2-bromo-and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromoselenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2,5dibromoselenophene generally gave 2,5-di(heteroarylated) selenophenes in high yields using both thiazole and thiophene derivatives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the synthesis of unsymmetrical 2,5-di(hetero)arylated selenophene derivatives in three steps from selenophene.", "id": 614} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmost of the children with cerebral venous thrombosis have an underlying chronic disease and those who are previously well have an acute infectious illness .\nobstructive hydrocephalus as a complication of cerebral venous thrombosis is rare and few cases are described .\na previously healthy 4-year - old boy presented with 5 days of headache and vomiting .\nmagnetic resonance imaging of the patient revealed obstructive hydrocephalus and magnetic resonance venography revealed thrombosis of the right transverse sinus [ figure 1 ] .\nlow molecular weight heparin was started at a dosage of 1 mg / kg twice a day .\ncontrol magnetic resonance imaging and magnetic resonance venography 1 month after the first event revealed partial resolution of hydrocephalus along with recanalization of the affected sinus [ figure 2 ] .\nhydrocephalus and absent flow in the right transverse sinus showing acute thrombosis improvement of hydrocephalus and recanalization of the affected sinus after a month of heparin therapy with folic acid and vitamin b6 and b12 replacement , the follow - up of the patient was given up by the family and he did not receive any treatment for 5 months .\nsix months after the first event , the patient was again admitted to hospital with a similar clinical picture along with new thrombosis at the sagittal sinus .\nthe patient is still followed up with low molecular weight heparin treatment after the second thrombosis attack .\ncerebral venous system thrombosis is an unusual event in childhood and clinical presentations , complications , diagnostic procedures , etiological investigations , and treatment modalities were not well established .\nclinical findings of cerebral venous system thrombosis include seizures , headache , vomiting , drowsiness , lethargy , and confusion .\nthe patient may show acute or subacute picture related to progression of the disease . the present case presented with acute symptoms secondary to increased intracranial pressure . increased intracranial pressure\nis a well - known complication of cerebral venous thrombosis , but accompanying hydrocephalus is rarely described .\nthe mechanism of hydrocephalus is considered to be secondary to an increase in venous pressure resulting in the blockade of cerebrospinal fluid flow into the sinuses by arachnoid villi .\nmost of the patients with cerebral venous thrombosis have an increased intracranial pressure without an increase in ventricular size .\nwhy some patients develop hydrocephalus is not clearly understood and only a few adult cases were described .\nthe etiologies regarding cerebral venous thrombosis are diverse and include head and neck infections and chronic disorders such as collagen tissue disorders , cardiac disease , and hematological abnormalities .\nhalf of the patients have prothrombotic states which include anticardiolipin antibodies , deficiencies of protein c and s , antithrombin iii and prothrombotic gene mutations such as prothrombin 20210 , factor v leiden , and mthfr mutations .\nthe most frequent two common mthfr polymorphisms are c677 t ( alanin to valin transition ) and a1298c ( glutamine to alanine transition ) .\nevaluation of nine case control studies with total 382 patients having cerebral venous thrombosis revealed that carrying mthfr was not a risk factor for cerebral venous thrombosis . on the contrary\na canadian study revealed that 29% of patients with cerebral venous thrombosis had mthfr polymorphisms .\nour case had a prothrombotic state with mthfr 1298 homozygous polymorphism without any risk factors .\noccurrence of clinical findings after cessation of heparin treatment suggests that mthfr polymorphism may be an important risk factor for cerebral venous thrombosis .\nanticoagulation is not recommended for asymptomatic and hemorrhagic cases . when used , low molecular weight heparin is the standard anticoagulant treatment in children .\ntreatment may last for 36 months or it may be continued until recanalization if risk factors are eliminated .\nour patient responded well to low molecular weight heparin with recanalization of sinuses and recovery of hydrocephalus in both the attacks . in conclusion\nmthfr 1298 polymorphism may be an important risk factor and low molecular weight heparin should be the choice of treatment in cases without hemorrhage .", "answer": "cerebral venous thrombosis is a rare form of stroke in childhood . \n increased intracranial pressure is a well - defined complication of cerebral venous thrombosis but obstructive hydrocephalus as a presentation finding of cerebral venous thrombosis is rarely described . a child case of cerebral sinus thrombosis presenting with obstructive hydrocephalus and management of clinical condition \n is presented with discussion of reported cases and treatment recommendations .", "id": 615} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninflammatory bowel disease ( ibd ) is a common diagnostic and therapeutic problem , affecting patients at increasingly young ages .\na standard diagnostic method includes macroscopic assessment of the intestinal mucosa during colonoscopy and histopathological evaluation of the obtained biopsies . according to porto criteria ,\nthe diagnosis of ibd is based on the clinical presentation , intestinal endoscopic and histological features , laboratory tests , and radiological examination .\nrecently , reports on the usefulness of a noninvasive examination , that is , faecal calprotectin measurement in ibd diagnosis , have been published .\nevaluation of faecal calprotectin ( fc ) seems to be a screening test selecting patients requiring further invasive diagnostics .\nfurthermore , there have been reports on using calprotectin assays in monitoring the treatment of crohn 's disease and ulcerative colitis in adults and children [ 14 ] . to our knowledge ,\nthere are no published data on the usefulness of faecal calprotectin assays in the diagnosis of other atypical forms of bowel inflammation , such as eosinophilic , lymphocytic , or nonspecific colitis .\nthe aim of the study is to assess the usefulness of faecal calprotectin measurement in children with various types of ibd and to evaluate fc concentration in children with crohn 's disease and ulcerative colitis in relation to disease activity .\n91 patients were included in the analysis , including 49 boys ( 53.85% ) and 42 girls ( 46.15% ) , ranging from 6 to 18 years of age ( the mean age was 13.38 years ) .\nthe study group comprised 71 children with various types of ibd , who were subsequently divided into six subgroups : b124 ( 33.8% ) children with crohn 's disease ( cd ) , b216 ( 22.5% ) with ulcerative colitis ( uc ) , b37 ( 9.8% ) with eosinophilic colitis ( ec ) , b48 ( 11.26% ) with lymphocytic colitis ( lc ) , and b516 ( 22.5% ) with nonspecific colitis ( nc , colitis indeterminata \nthe control group ( k ) comprised 20 healthy , age- and sex - matched subjects .\npatients with ibd underwent following procedures : anamnesis , physical examination , laboratory tests ( inflammatory state markers , biochemical parameters of liver , pancreas , and kidney function , sweat test , coprological tests , and immunoassays ) , diagnostic imaging ( abdominal ultrasound ) , and endoscopy with histopathological evaluation . in all patients ,\nfaecal calprotectin was measured by means of elisa method , using phical test ( calpro ) .\ncalprotectin concentrations ranging from 0 to 50 mg / kg were considered to be normal reference values .\nthe results were evaluated by using the following tests : komogorow - smirnow , t - student , u mann - whitney , fisher , and yates ; the analysis of correlation was based on the spearman 's rank correlation coefficient . a p value of < 0.05 was considered statistically significant .\nall patients and their caregivers gave informed consent to participate in the study , which was approved by the bioethics committee of the medical university of silesia in katowice ( consent no .\na statistically significant increase in the mean concentrations of faecal calprotectin was observed in the group of children with cd and uc , as compared to the control group .\nconcentrations of fc were also higher in children with uc than in patients with cd .\nfaecal calprotectin concentrations were within the normal limits in patients with eosinophilic , lymphocytic , and nonspecific colitis , similarly to the healthy subjects ( table 1 , figure 1 ) in children with cd , faecal calprotectin concentrations positively correlated with the disease severity assessed according to the pcdai scale . in patients suffering from uc , faecal calprotectin\nalso positively correlated with the truelove - witts scale and the rachmilewitz endoscopic index ( figures 2 , 3 , and 4 ) . a significant increase in faecal calprotectin concentrations\nwas observed in children suffering from cd , with lesions located in both small and large intestine , and in patients presenting with inflammatory changes in 5 or more sections of the intestine ( figure 5 ) .\nfaecal calprotectin is a promising , noninvasive screening method for diagnosing patients suffering from gastrointestinal disorders , such as abdominal pain or diarrhea , which are also typical for ibd [ 57 ] .\nso far , many authors have considered calprotectin as a useful marker in differential diagnosis of ibd and functional gastrointestinal disorders ( e.g. , irritable bowel syndrome ) [ 8 , 9 ] .\nmany authors evaluated faecal calprotectin concentrations in patients with suspected inflammatory process of the large intestine .\ndemonstrated in the group of paediatric patients that this assay is characterised by 95% sensitivity and 93% specificity , and high calprotectin concentrations show strong positive correlation with the presence of inflammatory lesions in the large intestine . according to these authors\nso far , only limited studies , based on very small groups of patients , evaluated faecal calprotectin concentrations in patients with other types of bowel inflammations less common than cd and uc , such as lymphocytic , eosinophilic , and nonspecific colitis , which seem to be a considerable clinical problem in everyday pediatric practice . in studies conducted by bunn et al . , two children with nonspecific colitis and 3 children with allergic colitis were included in the analysis . in both cases ,\ncalprotectin concentrations were found to be within the normal ranges . in our study involving 31 children : 7 with eosinophilic colitis , 8 with lymphocytic colitis , and 16 with nonspecific colitis , respectively ,\nthese results support the hypothesis that in the aforementioned types of bowel inflammation , histopathological examination does not reveal infiltrations of neutrophil cells , whose cytosols contain calprotectin . therefore , its concentration in faeces is directly related to the number of neutrophils in the large intestine lumen [ 11 , 12 ] . in paediatric patients , the diagnosis of nonspecific colitis ( indeterminata colitis ) remains unchanged in approximately 36% . over time in some patients , the diagnosis may be changed into ulcerative colitis ( in approximately 3372.5% ) or crohn 's disease ( in approximately 1727.5% ) . in our group of 6 cd patients , previously diagnosed conditions included single cases of ulcerative colitis , lymphocytic colitis , and nonspecific colitis , whereas eosinophilic colitis was found in 3 subjects .\nincreased calprotectin concentrations may be useful when making a decision on extending diagnostic procedures in patients with less frequent types of bowel inflammation . in our study ,\nthe mean calprotectin concentration in the examined patients with ibd was higher than it was observed by bremner et al . ; however , patients in remission were also enrolled in the latter research . in the presented material , a significant correlation was demonstrated between calprotectin activity and the disease severity assessed by the modified pcdai scale for cd and the modified truelove - witts scale and the rachmilewitz endoscopic index for uc .\n, demonstrating a strong positive correlation between calprotectin concentrations and the disease severity according to the modified truelove - witts scale only in uc . analyses performed in children assessed a correlation between fc concentrations and intensity of macroscopic and microscopic inflammatory lesions in the large intestine , observed in the course of ibd .\nstudies carried out by fagerberg et al . included 39 children with ibd , in whom calprotectin concentrations strongly correlated with intensity and extent of micro- and macroscopic abnormalities .\nnorwegian researchers also confirmed such a correlation and , moreover , suggested that intensity of inflammatory lesions rather than their extent influences faecal calprotectin concentration .\nthis suggestion can be supported by data obtained from our study , indicating that in patients with uc calprotectin concentration depends on disease activity and not on the extent of lesions , in contrast to patients suffering from cd . in the latter group , calprotectin concentrations correlated with the disease activity and\nwere significantly higher in children with inflammatory lesions present in both small and large intestine and located in 5 or more sections of the large intestine .\nthese results support conclusions from the studies on clinical expression of the disease , which demonstrated that in children and adolescents the disease is more severe and cd lesions are located in the small intestine [ 17 , 18 ] . so far\nfaecal calprotectin measurement seems a promising test to evaluate disease activity and a tool for monitoring ibd treatment . in everyday practice ,\na disadvantage of this method is its low specificity , which is connected with the fact that in patients with increased calprotectin concentration many organic diseases should be excluded .\nit seems that measurement of faecal calprotectin concentration can be a useful , safe , and noninvasive test in children suspected for ibd , since it is found to be increased in children with cd and uc as compared to patients with other inflammatory diseases ( eosinophilic , lymphocytic , and nonspecific colitis ) and also in the reference to healthy subjects . when the faecal calprotectin concentration is increased in children with less common types of bowel inflammation , a further follow - up of such patients\nfaecal calprotectin concentration correlates positively with the disease severity in cd and uc patients ; thus , it may be useful when choosing or modifying the appropriate treatment regimen .", "answer": "introduction . \n the aim of the study was to assess the usefulness of the fc measurement in children with various types of ibd and relation to the disease activity . \n patients and methods . \n 91 patients ( 49 boys : 53.85% and 42 girls : 46.15% , mean age : 13.38 years , range 618 years ) were included in the analysis . \n patients were divided into the groups : b124 children with cd , b216 patients with uc , and a group comprising 31 children with other types of colitis ; the control group ( k ) comprised 20 healthy children . \n fc was assayed by elisa method , using phical test ( calpro ) . \n results . \n the mean faecal calprotectin concentrations were higher in children with cd and uc as compared to healthy controls , patients with eosinophilic , lymphocytic , and nonspecific colitis . \n a positive correlation was observed between fc concentrations and the disease activity ( the pcdai scale , the truelove - witts scale , and the endoscopic rachmilewitz index ) . \n conclusion . \n it seems that the fc concentrations can be a useful , safe , and noninvasive test in children suspected for ibd , since fc concentration is higher in children with cd and uc than in patients with other inflammatory diseases .", "id": 616} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe two main and comprehensive goals of health provision are promotion of quality of a healthy life and prolonging it , and deletion of health disturbing factors .\n, it was believed that neonates and infants either could not feel pain or felt it less than adults due to incomplete development of their nervous system\n. meanwhile , it has been found that the pain - conducting fibers are formed in the fetal period , and term neonates are sensitive to pain and experience it like infants and children . on an average\n, the neonates admitted in the neonatal intensive care unit ( nicu ) experience 115 painful procedures during their 16-day stay in this ward , of which 79.2% are administered no dedicational and non - dedicational sedative methods . in about 2.1% of these procedures , the neonates receive sedative medications , in 18.2% of the procedures , they receive non - dedicational sedation , and in 20.8% of the cases , they receive both dedicational and non - dedicational interventions .\nthe procedure conducted most frequently among neonates in the nicu is heel stick ( 56% ) .\npain in neonates , if not treated , leads to immediate and long - term complications .\nthe immediate complications include intraventricular hemorrhages and high mortality in the nicu , long - term response to pain , and poor responses to stimulants .\nlong - term complications include learning problems , reduction of concentration , lack of adaption with new situations , and mood changes in neonates and children .\nif not managed , pain and tension in neonates can disturb their sleep condition , growth and development , nutrition tolerance , and even vital signs such as respiration , heart rate ( hr ) , bp , and o2 saturation .\nfurther education and better detection of pain signs are essential for the health care personnel due to the short- and long - term complications of the uncontrolled pain among neonates .\nprevention of these destructive effects may also help in reduction of hospitalization period and costs .\nneonates can be relieved of pain through non - dedicational methods such as intake of oral sucrose , non - nutritive sucking , breast feeding , mother infant skin touch , and music during the procedures . among the effective methods of pain relief in neonates is playing a melody which can act as a tool for distracting the neonates and enhancing the secretion of endorphins . playing a melody on a piano and recorded lullaby voice results in rapid return of the hr and behavioral and facial reactions due to pain to the baseline values .\nstudies on the effect of music on neonatal physiological responses concluded that music is effective on hr increase and changes of respiratory rate .\nreported a significant difference in neonates hr during removal of a needle as well as in the first 5 min after heel stick .\na study in the nicu showed no notable changes in neonates hr after playing music compared to before it .\ntaking into consideration the destructive and numerous effects of pain on neonates various physiological systems , as well as the existence of controversial results regarding the sedative effects of music therapy , and the importance of pain management and prevention of numerous and irreversible complications in neonates , the researcher investigated the effect of melody on the physiological responses of heel stick pain in neonates which is among the most frequent painful procedures done on them .\nthis is a quasi - experimental study conducted for 5 months in the nicu of alzahra hospital in isfahan , iran .\nsampling was by consecutive convenient sampling , and the subjects comprised 50 neonates meeting the inclusion criteria , who were assigned to study and control groups through random allocation .\nthe neonates in the group of melody ( study ) and the neonates in the control group were selected on the first and second days of the study , respectively .\ninclusion criteria were gestational age of 34 weeks , being hospitalized in the ward ( inpatient hospitalization ) , not receiving o2 before and during the study , intact hearing ability ( through startle test ) , proper neonatal consciousness , and administration of no other painful procedures before conducting the intervention .\nexclusion criteria were parents not willing to continue participating in the study or a need for oxygen therapy in the neonates due to any reason during the intervention and no success in the first heel stick trial .\nresearcher conducted the intervention after obtaining consent form the neonates parents and explaining the study goals and method .\nthe tool adopted in this study was a questionnaire to record the personal characteristics and a form of physiological signs record including hr , respiratory rate / min , and atrial o2 saturation percentage in the neonates .\nneonates hr and atrial o2 saturation were monitored by a saadat monitoring device connected to the neonates , which was calibrated monthly by medical equipments engineers of the hospital .\nthe melody adopted was the piece golden dreams played on piano with no lyrics . in the intervention group ,\nthe melody was played on an mp3 player laid at a distance of 1 m from neonates cot with a sound intensity of 65 db .\nit was played 3 min before the heel stick was administered until 3 min after the end of the procedure by an experienced nurse ( voice intensity was measured by a db meter device ) .\nthen , the neonates heels were disinfected by alcohol disinfection cotton and the lancet was inserted from the lateral side of the heel , and the researcher measured and recorded the neonatal physiological responses ( pulse , atrial o2 saturation , and respiratory rate ) by saadat monitoring device 3 min before , during , and after the heel stick , respectively . in the control group ,\nall variables ( physiological responses ) were evaluated and recorded in time points similar to the study group .\nthe obtained data from both groups were entered into a computer and analyzed by chi - square , repeated measure analysis of variance ( anova ) , and independent t - test using spss 15 .\ninformed consent was obtained from participants and the study has confirmation of ethics committee of isfahan university of medical sciences ( no 391316 ) .\ninformed consent was obtained from participants and the study has confirmation of ethics committee of isfahan university of medical sciences ( no 391316 ) .\nresults showed that most of the subjects were males ( 58% ) , and the chi - square test showed no significant difference between the two groups ( p > 0.05 ) .\nindependent t - test showed no significant difference in some demographic characteristics ( gestational age , birth weight , current weight , and neonates age ) of the subjects in the two groups ( p > 0.05 ) .\nrepeated measure anova showed a significant difference in hr in the melody and control groups at different time points ( p < 0.05 ) [ table 1 ] .\nleast significant difference ( lsd ) post hoc showed a significant difference in the means of hr during and before intervention , and during and after intervention in the melody group ( p < 0.05 ) .\nit also showed a significant difference in the means of hr during intervention and before intervention ( p < 0.05 ) , but not at other time points ( p > 0.05 ) .\nindependent t - test showed no significant difference in the means of hr in the melody and control groups before intervention ( p = 0.69 ) , during intervention ( p = 0.87 ) , and after intervention ( p = 0.42 ) .\nrepeated measure anova also showed no significant difference in atrial o2 saturation at various time points in the melody group ( p > 0.05 ) , but the difference was significant in the control group ( p < 0.05 ) [ table 2 ] .\nlsd post - hoc test showed that the difference before and after intervention had a significance level of 0.05 .\nindependent t - test showed no significant difference in the means of atrial o2 saturation between the melody and control groups before intervention ( p = 0.12 ) , during intervention ( p = 0.37 ) , and after intervention ( p = 0.63 ) .\nrepeated measure anova showed a significant difference in respiratory rate at various time points in the melody and control groups ( p < 0.05 ) [ table 3 ] .\nlsd post - hoc test showed a significant difference in the means of respiratory rate before and during intervention , and during and after intervention in the melody group ( p < 0.05 ) .\nit also showed a significant difference in the means of respiratory rate before and during intervention , and before and after intervention in the control group ( p < 0.05 ) .\nindependent t - test showed no significant difference in the means of respiratory rate in the melody and control groups before ( p = 0.96 ) , during ( p = 0.69 ) , and after ( p = 0.87 ) intervention ( p > 0.05 ) .\ncomparison of means of neonates heart rate in the two groups at various time points comparison of means of neonates o2 saturation in the two groups at various time points comparison of means of neonates respiration rate in the two groups at various time points\nresults showed that the means of hr and respiratory rate were higher during intervention compared to before and after intervention in the melody group . the increase in mean\npulse during administration of the procedure was higher in the control group compared to the melody group .\nmeans of respiratory rate showed an increase both in the study and control groups , although the increase remained longer after ending the procedure in the control group compared to the study group .\nkeith et al . also reported that music positively affected hr and respiratory rate and could balances these values , which is in line with the findings of the present study .\nour obtained results showed no significant difference in the means of atrial o2 saturation at various time points in the melody group , possibly due to the type of selected melody , music , or length of the played music .\nfor instance , standly applied a piece of music containing lullaby sang by a woman , and in the study of karimi et al .\nseveral other studies , like the study of collabra on the effect of music on premature neonatal physiological responses , showed that music had no effect on the neonates atrial o2 saturation , respiratory rate , and hr .\nkarimi et al . also showed no effect of music on hr and atrial o2 saturation , which is consistent with the findings of the present study .\nin addition , obtaining no significant difference in neonatal physiological responses before , during , and after intervention in the study and control groups ( p > 0.05 ) may be due to the type of selected melody or the low number of the subjects , as the difference may become significant with a higher sample size .\nin general , the findings of the present study showed that playing a melody causes a balance in the neonatal physiological responses including respiratory rate and hr during heel stick .\ntherefore , a melody is recommended to be played for neonates during administration of painful procedures , to prevent the destructive effects of pain .\nour obtained results showed that playing music is an efficient intervention to maintain balance in neonates respiratory rate and hr during administration of painful procedures .\nthese findings reveal the importance of the application of music in the caring of neonates .\nmusic therapy decreases the negative effects of treatment procedures and playing musical melodies is a cost - effective and convenient independent nursing intervention which does not need a physician 's visit and extra staff , and is not so time consuming .", "answer": "background : during health care in the neonatal intensive care unit ( nicu ) , infants undergo extremely painful procedures , which may cause problems , if not controlled , such as changes in the pattern of respiratory rate , heart rate , and blood oxygen saturation . \n the present study aimed to find the effect of melody on the physiological responses of neonates heel stick pain.materials and methods : this quasi - experimental study was conducted in alzahra hospital ( isfahan , iran ) for 5 months . \n fifty infants were selected through convenient sampling method and were randomly assigned in equal numbers to two groups ( n = 25 ) . in the melody group ( intervention ) , a selected melody was played for the infants at a distance of 1 m from them , with a sound intensity of 65 db , from 3 minutes before , during , and after the heel stick procedure , respectively , and their physiological responses were observed with a monitoring system and recorded at the afore - mentioned time periods . \n physiological responses were also recorded in the control group ( no intervention ) 3 min before , during , and after the heel stick procedure , respectively.results:means of respiratory and pulse rates in the melody and control groups showed a significant difference at different time points . \n but the mean blood oxygen saturation in the melody group showed no significant difference at different time points , although the difference was significant in the control group.conclusions:the results showed that melody could maintain more balance in some physiological responses of infants , such as the respiratory rate and pulse rate during the guthrie test . therefore \n , melody is recommended to be used to prevent the destructive effects of pain in infants during painful procedures .", "id": 617} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsubcellular localization is a key feature for characterizing physiological functions of proteins : in eukaryotes compartmentalization finalizes the sets of possible interacting molecules and therefore the biological process(es ) in which a protein is involved .\nto date it has been carried out only for a narrow subset of known proteins . presently only unicellular species have been extensively analyzed by means of high - throughput experiments , such as s.cerevisiae ( 1,2 ) .\ndifferent approaches , such as green fluorescent protein ( gfp)-tagging ( 2 ) and immunoluminescence ( 1 ) , agree only on 75% of the annotations and this is mainly due to experimental limitations and possible interference of the tagging procedures on the normal protein trafficking ( 3,4 ) .\nalthough it is difficult to scale these techniques to more complex organisms , a partial map for mouse liver cells was recently produced ( 5 ) .\ncurated annotations of the subcellular localization , although probably not covering all the available experimental knowledge , are contained in the swissprot database .\nthe amount of proteins with an experimental annotation listed in swissprot is different for different species and reaches at the most half of the total amount of proteins in a genome ( see below ) .\nthe question remains , however , as to how one can obtain a reliable annotation of subcellular localization for the rest of the proteins .\nalthough in principle a change in few residues could result in a change of the localization of a protein , in practice with very few exceptions natural proteins with a sequence identity > 30% share the same localization ( 68 ) . in the most successful cases ,\nabout two - thirds of a genome can be annotated both by experimental results and similarity search .\nmany predictors have been developed recently [ ( 4,711 ) , a list is available at ] .\na prerequisite for a predictive method is its capability of well performing when the query sequence shares very low sequence similarity to known proteins .\nit is therefore important to implement and adopt predictors tested with a rigorous cross - validation procedure on sets of proteins < 30% identical with respect to the sequences used for the training .\nanother important feature to be considered in adopting a predictor is how the relative abundance of localization among different sub - compartments was treated during the training phase . indeed , with the available data it is difficult to estimate the real proportions between the proteins targeted into the different subcellular localizations ; most of the predictive methods tend in fact to overestimate localization types for which more examples are known ( 8) .\nit is therefore necessary to adopt predictive methods that attempt to correct bias towards one or more localization classes .\nthey include ( i ) the results of large - scale experiments for the determination of subcellular localization in specific organisms [ ygfp ( 1 ) , for yeast ; and ormdb ( 5 ) , for mouse ] ; ( ii ) the annotations of proteins to be found in organelles [ plprot ( 12 ) , for proteins from plastids ; organelledb ( 13 ) , for proteins in different organelles ; and mitop2 ( 14 ) , for mitochondrial proteins ] .\na database collecting all the annotations listed in swissprot is also available [ dbsubloc ( 15 ) ] .\nfinally databases that implement predictors of subcellular localization based on different methods have been reported [ loctarget ( 16 ) and pa - gosub ( 17 ) ] .\nloctarget ( 16 ) is specific for structural genomics targets and lists some 50 000 proteins from different organisms .\npa - gosub ( 17 ) contains the annotations of eukaryotic subcellular localization and protein function of different genomes and is based on homology search and bayesian artificial networks for prediction .\nwe recently developed bacello , a well - performing balanced method for the prediction of subcellular localization , outperforming previously existing methods for the same task ( 8) .\nwe adopt bacello to annotate whole genomes in association with methods specifically implemented for the prediction of the topology of integral membrane proteins . in this paper\nwe present eukaryotic subcellular localization database ( esldb ) , a database of protein subcellular localization which provides an annotation for the entire proteomes of eukaryotic organisms . for each sequence\nour database contains the experimental localization , when available , the homology - based annotation , when feasible , and the predicted localization computed with the in - house developed machine learning based methods . by this the new database provides more features than other existing databases . to date , five proteomes were fully processed : homo sapiens , mus musculus , caenorhabditis elegans , saccharomyces cerevisiae and arabidopsis thaliana . in summary , esldb is , to our knowledge , the first database containing the available experimental and similarity - based annotations for eukaryotic proteomes listing for each protein sequence also the predicted subcellular localization .\nfive different genomes were downloaded as specified : h.sapiens ( ensembl ncbi36 ) , m.musculus ( ensembl ncbim36 ) , s.cerevisiae ( ensembl sgd1 ) , c.elegans ( ensembl cel150 ) and a.thaliana ( tair6 ) . for each protein\nthe corresponding swissprot entry in release 50 was found , when existing , searching for exactly matching sequences .\nthe amount of genomic sequences that is deposited in the swissprot database ranges from 13% for both a.thaliana and c.elegans to 79% for s.cerevisiae ( table 1 ) .\nnumber of proteins with an experimental or a similarity - based annotation of the subcellular localization the sequences experimentally annotated are included among those annotated by similarity . for these proteins the experimental annotation was extracted by parsing the \nthe annotations directly or implicitly referring to one of the following 17 classes were taken into account : nucleus , cytoplasm , mitochondrion , plastid , golgi , endoplasmic reticulum , lysosome , endosome , vesicles , peroxisome , vacuole , cell wall , secretory pathway , extracellular , cytoskeleton , membrane and transmembrane ( table 1 in supplementary data lists the keywords that have been considered for assigning the localization ) .\nonly 22% of all the swissprot entries for the five considered species record the experimental subcellular localization .\nthe rate of experimental annotation ranges from 46% of the s.cerevisiae proteome to < 10% for a.thaliana and c.elegans ( table 1 ) .\nthe experimental annotation column in table 2 lists the amount of proteins experimentally annotated in each one of the 17 types of considered localization .\nit is worth mentioning that the same sequence can be annotated in swissprot with two ( or rarely more ) different localizations .\nfor example , this happens for proteins that shuttle between the nucleus and the cytoplasm . in these cases\nit is evident that the amount of proteins in the different localizations spans two orders of magnitude .\nnumber of sequences in the 17 different subcellular localizations as derived with experimental and similarity - based annotations the sequences experimentally annotated are included among those annotated by similarity .\nthe best way to annotate the remaining proteins is to search for experimentally annotated sequences sharing high identity ( 68 ) .\nsince the three eukaryotic kingdoms ( metazoa , viridiplantae and fungi ) differ in number and types of possible localizations , three kingdom - specific datasets of annotated proteins were extracted from swissprot .\nthese dataset contains 26 192 sequences for metazoa , 6370 sequences for viridiplantae and 4023 sequences for fungi .\nall the sequences of the five considered genomes were searched for similar sequences in the appropriate dataset using blast ( 18 ) . when matches were found with an e - value < 10 ( roughly corresponding to an identity level > 30% ) the annotation of the best - scoring match was transferred to the query sequence . when multiple matches are found with the same best scoring e - value ,\nsimilarity - based annotation column in table 2 contains the number of proteins annotated with the above described procedure in each localization ( including the sequences experimentally annotated ) .\nalso in this case , sequences that end up with a multiple annotation are counted several times .\nit appears that a large portion of the sequences , ranging from 32% in h.sapiens up to 67% in a.thaliana , is not endowed with similar counterparts with an annotated localization . in this case\nsubcellular localization can be predicted with specifically suited methods . for generating our annotation system we developed a pipeline that comprises previously described methods ,\nall based on machine learning tools and that are proved to outperform most of the available predictors for the same task when rigorous cross - validation procedures are adopted ( 8) . the pipeline is shown in figure 1 .\nfirst of all , membrane proteins are discriminated with spep ( 19 ) and ensemble ( 20 ) : the former is a neural network based method for predicting the presence of signal peptide while the latter is a method based on neural networks and hidden markov models for the prediction of the topology of all - alpha transmembrane proteins .\nwhen a signal peptide is predicted , it is cleaved from the sequence before predicting the presence and the location of the transmembrane helices .\nif no transmembrane helix is found , the uncleaved sequence is analyzed using bacello ( 8) , a recently developed tool for predicting the subcellular location of eukaryotic proteins .\nthis is based on a decision tree of support vector machines and it discriminates four localizations in metazoa and fungi ( cytoplasm , nucleus , extracellular and mitochondrion ) and five localizations in viridiplantae ( the same as before plus chloroplast ) .\nbacello , spep and ensemble are predictive methods described previously ( 8,17,18 ) . at the end of the pipeline up\nto five localizations can be discriminated in metazoa and fungi and up to six in viridiplantae . although the possible types of localization are 17 ( see above ) , the actual reduction in the number of discriminated localization is due to the lack of an adequate number of non - redundant examples for training .\na novelty of bacello is that first takes into consideration that the actual proportion of proteins targeted towards each compartment remains unknown by adopting an equiprobability hypothesis and a balancing procedure ( 8) . the structure of the predictive system allows annotating the subcellular localization in a hierarchical way .\nfirst , all membrane proteins are separated from soluble ones ; the latter are then divided into intracellular and secreted .\nintracellular proteins are separated in nucleocytoplasmic and organellar ; the former are then separated in cytoplasmic and nuclear while the latter , in the case of viridiplantae , are further divided into mitochondrial and chloroplastic .\nthe topology of the decision tree and the balancing procedure were adopted for maximizing the prediction performances as evaluated on testing sets independent of the training sets .\nthe best scoring binary decisions are at the top of the tree , the worst - scoring at the bottom .\nthe predictions are stored in the database along with the hierarchy of the decisions in the pipeline .\nall the proteins of a genome , also when experimental and/or homology - based annotation are possible , are annotated by means of the predictive method . in table 3\nnumber of sequences in the six predicted subcellular localizations table 4 contains the evaluation of the coverage and the accuracy of the prediction for the proteins of h.sapiens , as compared with both the experimental and the similarity derived annotations .\nwe considered 6444 unique proteins experimentally annotated and 25 134 unique sequences for which a similarity - based annotation is available .\nthe coverage is computed as the fraction of correctly predicted sequences in each class over the number of proteins belonging to the class .\nthe accuracy is the fraction of correctly predicted proteins over the total number of proteins predicted in the class .\nthe agreement between the annotations and the prediction is good , especially when predictions are compared with the experimental annotations and the higher levels of the hierarchical prediction are considered .\nperformance of the prediction pipeline as compared with the experimental and the similarity - based annotations the indentation of the subcellular localization names reflects the hierarchy of the prediction ( see figure 1 ) .\ncoverage = ( no . of proteins of class i predicted as class i)/(total no .\nall the data are available at the website ( ) and can be accessed by protein code , as derived from the original and above - mentioned versions of the genomic databases , or by protein description , as derived from the swissprot entries . alternatively the sequence of interest can be submitted and , by means of the md5 encoding , the match engine searches for identical sequences deposited in the database .\nmoreover , complex searches can be performed combining the different annotation methods and the different localizations .\nthe entries matching the query keys can either be displayed or downloaded in a tabular format that contains the experimental and the similarity - derived annotation and the localization prediction for each match .\npages containing more details about each one of the proteins ( figure 2 ) are linked to the protein codes and contain the sequence , the description and the link to the swissprot file when an experimental annotation exists .\nwhen the sequence can be annotated by similarity , the swissprot entry corresponding to the most similar sequence is reported together with the e - value as computed by blast ( 18 ) . in both the tabular and the detailed pages\n, the results of the prediction are given together with the complete path through the decision tree .\nthis information can be useful since , as we commented in the previous section , the accuracy of the prediction lowers as the number of discriminated classes increases .\nthis means that annotations in the macro - classes are endowed with a higher reliability .\nall the data contained in the database can be freely downloaded in flat file format .\nthe database resides in a postgresql server and the web interface has been implemented using python , html 4.0 and css 2.0 languages .\nmore available eukaryotic proteomes are currently under process and will be added to the database .\nmoreover we plan to regularly update the database as new versions of swissprot or new releases of the considered proteomes will be available .", "answer": "eukaryotic subcellular localization database collects the annotations of subcellular localization of eukaryotic proteomes . so far \n five proteomes have been processed and stored : homo sapiens , mus musculus , caenorhabditis elegans , saccharomyces cerevisiae and arabidopsis thaliana . for each sequence , \n the database lists localization obtained adopting three different approaches : ( i ) experimentally determined ( when available ) ; ( ii ) homology - based ( when possible ) ; and ( iii ) predicted . \n the latter is computed with a suite of machine learning based methods , developed in house . \n all the data are available at our website and can be searched by sequence , by protein code and/or by protein description . \n furthermore , a more complex search can be performed combining different search fields and keys . \n all the data contained in the database can be freely downloaded in flat file format . \n the database is available at .", "id": 618} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n aloe vera gel is a colorless substance obtained from the parenchymatous cells in fresh leaves of aloe vera ( l ) burm .\nnative to north africa , aloe has been introduced and is being cultivated in the warmer areas of the world . aloe vera gel , rich in polysaccharides ( pectins , hemicelluloses , glucomannan , acemannan , and other mannose derivatives ) should not be confused with the drug aloe dried juice of aloe vera leaves , bitter yellow exudate containing anthracene glycosides , mainly of the aloe - emodin anthrone 10-c - glucoside type [ 1 , 2 ] . \n\nconsumed as a beverage it was not toxic in vivo for mice . on the contrary , aloe latex and its hydroxyanthrone derivatives ( aloin , aloe - emodin etc . )\nhave strong laxative properties and their longer use requires medical supervision . traditionally , aloe gel was widely used for the treatment of minor wounds , inflammatory skin disorders , and thermal and radiation burns . in vitro ,\naloe gel suppressed bacteria - induced pro - inflammatory [ tumor necrosis factor ( tnf- ) and interleukin 1 ( il-1 ) ] cytokines and matrix metalloproteinase 9 ( mmp-9 ) production in human mononuclear leukocytes [ 4 , 5 ] . \n in vivo , polysaccharides derived from aloe vera gel , injected into mice , potently stimulated migration of macrophages to the peritoneal cavity . in human , oral aloe vera gel was used by patients with inflammatory bowel disease , osteoarthritis , and other inflammatory conditions .\noral and topical administration of aloe vera gel diminished inflammation and eased joint immobility and pain [ 811 ] . in ophthalmology\n, aloe vera extracts may be used in eye drops to treat inflammations and other cornea ailments . besides its anti - inflammatory activity\n, aloe vera gel has antimicrobial properties and in vivo exerts a protective effect on polymicrobial sepsis in mice [ 1317 ] .\nanthraquinones , compounds present in the outer part of aloe leaves and in their succus or extract , have been shown to have direct anti - cancer activity in different kinds of human cancer cell lines . moreover , aloe - emodin , a hydroxyanthraquinone from aloe vera , can act as an anti - angiogenic agent .\nsome data suggest that the inner part of aloe vera leaves , aloe vera gel and their polysaccharide components also have tumor growth modulatory properties , probably connected with their immunomodulatory activity [ 20 , 21 ] . in our previous paper\nwe reported the inhibitory effect of aloe barbadensis fresh leaves aqueous extract ( herbal drug biostymina ) on tumor - induced cutaneous angiogenesis in mice .\nthe aim of the present study was to evaluate in balb / c mice the in vivo influence of commercial aloe vera gel product ( aloe vera drinking gel ) on the syngeneic l-1 sarcoma tumor growth and its vascularization : a ) early cutaneous neovascular response , tumor - induced angiogenesis ( tia test ) , and b ) tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting .\n\n drug . tru - alo 99% aloe vera drinking gel ( aloe barbadensis miller folium succus ) , aloin content < 40 ppm ; produced by hi tech aloe vera pty ltd , bundaberg , australia\nthe study was performed on 59 female inbred balb / c mice 6 - 8 weeks old , weighing about 20 g , delivered from the polish academy of sciences breeding colony .\nfor all performed experiments animals were handled according to the polish law on the protection of animals and nih ( national institutes of health ) standards .\nmice were housed 4 - 5 per cage and maintained under conventional conditions ( room temperature 22.5 - 23.0c , relative humidity 50 - 70% , 12 h day / night cycle ) with free access to standard rodent diet and water .\nketamina 10% , biowet , pulawy , poland ) ; xylazine 10 mg / kg ( prep .\nsedazin , biowet , pulawy , poland ) ; 3.6% chloral hydrate 0.1 ml per 10 g of body mass ( sigma aldrich , usa ) ; morbital ( biowet pulawy , poland ) . \n\nevaluation of sarcoma l-1 growth and angiogenic activity was performed as previously described [ 23 , 24 ] .\nl-1 sarcoma cells were delivered from warsaw oncology center collection , passaged twice in vivo and grafted subcutaneously ( for evaluation of tumor growth and its hemoglobin ( hb ) content ) or intradermally ( for evaluation of their angiogenic activity ) to syngeneic balb / c mice . \n\nbriefly , sarcoma l-1 cells from in vitro stock were grafted ( 106/0.1 ml ) subcutaneously into the subscapular region of balb / c mice .\nafter 14 days the tumors were excised , cut to smaller pieces , rubbed through the sieve and suspended in 5 ml of phosphate buffered saline ( pbs ) .\nafter sedimentation , the supernatant was collected and centrifuged for 10 min at 1500 rpm . obtained sarcoma cells were washed once with pbs for 10 min , then centrifuged at 1500 rpm , and resuspended in parker medium in concentration of 4 10/ml or 10/ml .\nmultiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension\nmice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .\nall newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .\nidentification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .\nneovascular reaction 3 days after the intradermal injection of tumor cells 0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .\ntumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) . \n\nbriefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000 g. 20 l of the supernatant was added to 5 ml of drabkin reagent .\nthe absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .\nthe reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .\nmultiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension\nmice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .\nall newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .\nidentification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .\n0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .\ntumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) . \n\nbriefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000 g. 20 l of the supernatant was added to 5 ml of drabkin reagent .\nthe absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .\nthe reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .\ntwo - tailed p value was lower than 0.0001 ( t = = 4.467 ; df = 70 ) .\nhence , the mean number of newly formed blood vessels in the experimental , aloe - fed group of mice was highly significantly lower than in the corresponding controls ( fig .\n2 ) mean number of newly - formed blood vessels counted 3 days after the intradermal injection of sarcoma l-1 cells the difference between the groups of control and aloefed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance ( fig .\nno difference was observed in hemoglobin content between control and experimental tumors ( 21.3 3.1 vs. 24.1 3.6 g / mg , respectively ) . the effect of feeding mice with aloe vera drinking gel for 14 days after l-1 sarcoma subcutaneous grafting on the tumor volume ( difference on the border of statistical significance )\nit was shown by other authors that some aloe vera active components slow down the experimental tumor growth . three anthraquinones ( aloesin\n, aloe - emodin and barbaloin ) extracted from aloe vera leaves may exert their chemo - preventive effect through modulating antioxidant and detoxification enzyme activity levels .\naloe - emodin induces cell death through s - phase arrest and apoptosis in the dose- and time - dependent manner .\nother researchers describe the anti - tumour effect of specific derivatives of the aloe vera plant .\ndi(2-ethylhexyl)phthalate isolated from aloe vera linne may have anti - leukemic and anti - mutagenic properties .\nthe anti - tumor effect was also documented for the aloe vera leaf pulp extract and the main lectin ( aloctin i ) present in it , in the ehrlich ascites tumor model .\nacemannan , the compound of the extract from the parenchyma of aloe vera / aloe barbadensis , stimulates the synthesis of monokines and recruitment of immune cells and , by this mechanism , necrosis and regression of murine sarcoma .\nthe results of these studies suggest that this effect could be due to its immunomodulatory activity .\nacemannan has been approved by the fda - us as a potent immunomodulating and anti - viral agent .\nit was approved as an aid in the treatment of canine and feline fibrosarcoma . however , the critical condition for the tumor to effectively metastasize is formation of the new vessels prompted by a group of cancer cells derived from the primary , transported by the blood circulation and grafted in permissible tissue environment .\nthis permissiveness is conditioned by the agents released by the tumor cells that drive recipient tissue to facilitate new vessel growth in it .\nwe have been able to show that aloe vera drinking gel slows down an early phase of new vessel formation and their in - growth in hosting tissue .\nhowever , aloe vera drinking gel has not caused the necrotical effect on the tumor volume and it has not influenced the vascularity of the mature tumor ( as indicated by the lack of differences in hemoglobin content of tumors between groups ) .\nit may suggest that its effect is exerted only on the newly forming vessels during micrometastasis implantation .\nfew cytotoxic and targeted drugs have been proven effective in adjuvant systemic therapies after most of the tumor was removed by surgery or radiotherapy .\nthe presence of micrometastases at the time of primary therapy is emphasized as the cause of failure of loco regional therapies .\nthe effective chemoprevention should be directed at the micrometastasis priming mechanism , that is among most important angiogenesis .\naloe vera drinking gel , having a low profile of side effects , may be a good candidate for supplemental therapy . however , aloe vera is also known for its beneficial wound healing impact that might be partly attributed to its compound , -sitosterol , pro - angiogenic properties .\nit was shown that in the presence of heparin , beta - sitosterol stimulated neovascularization in the mouse matrigen plug assay , and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay .\ntherefore , further detailed studies on the specific compounds contribution of the antiangiogenic effect and its mechanism are warranted .\nperformed a randomized study of chemotherapy versus chemotherapy plus aloe arborescens , in 240 patients with lung , colorectal , gastric and pancreatic metastatic cancers .\naloe arborescens was given orally at a dose of 10 ml thrice daily of a mixture consisting of 300 g of aloe fresh leaves in 500 g of honey plus 40 ml of 40% alcohol , every day without interruption , either during or after chemotherapy , until the progression of disease , starting 6 days prior to the onset of chemotherapy .\nthe results of this study suggest that aloe may be successfully associated with chemotherapy to increase the tumor regression rate and survival time .", "answer": "aloe vera ( aloe arborescens , aloe barbadensis ) is a medicinal plant belonging to the liliaceae family . \n aloe vera gel prepared from the inner part of aloe leaves is increasingly consumed as a beverage dietary supplement . \n some data suggest its tumor growth modulatory properties . \n the aim of the present study was to evaluate in balb / c mice the in vivo influence of orally administered aloe vera drinking gel on the syngeneic l-1 sarcoma tumor growth and its vascularization : early cutaneous neovascular response , tumor - induced angiogenesis ( tia test read after 3 days ) , and tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting.feeding mice for 3 days after tumor cell grafting with 150 l daily dose of aloe vera gel significantly diminished the number of newly - formed blood vessels in comparison to the controls . the difference between the groups of control and aloe - fed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance . \n no difference was observed in tumor hemoglobin content .", "id": 619} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin this issue of critical care , protti and colleagues report the effects of metformin on human platelets both in vitro and ex vivo . in vitro experiments\nwere performed on healthy platelets incubated with increasing doses of metformin , whereas ex vivo experiments were done on platelets from patients presenting accidental metformin - induced lactic acidosis . in both situations ,\nplatelets ' lactate production and mitochondrial functions were measured . in vitro , a dose - dependent relationship between metformin con centration and lactate production was found . in both conditions ,\nhigh levels of metformin decreased mitochondrial respiratory chain complex i activity , mitochondria polarization , and oxygen consumption .\nmetformin is a biguanide that has been used as a first - line drug for type 2 diabetes treatment since 1957 in europe and 1995 in the us .\nmetformin was reputed to induce lactic acidosis , partly because phenformin , another biguanide , was withdrawn from the market because of an unacceptable rate of this complication .\nhowever , numerous clinical studies reported a similar incidence of lactic acidosis in diabetic patients with or without metformin , leading some authors to deny the existence of metformin - associated lactic acidosis . however , in usual clinical practice , metformin contraindications are not often respected .\nmoreover , physicians do not really monitor adequately their prescription . as a result , numerous publications reported the association between metformin and lactic acidosis . when a cause of lactic acidosis such as shock state or acute renal failure is present , the responsibility of metformin could be questioned .\nbut when healthy patients without risk factors develop metformin poisoning leading to lactic acidosis , there is no doubt about this link .\nhowever , metformin inhibits hepatic gluconeogenesis in different animal species and decreases mitochondrial respiratory chain complex i activity in different organs .\nthe clinical research on metformin - associated lactic acidosis was limited to retrospective studies describing incidence , risk factors , and supportive treatments .\na big step forward was made when the gattinoni group reported a decrease in oxygen consumption after metformin poisoning in humans , strongly suggesting that metformin was able to induce mitochondrial dysfunction in humans .\nthe study by protti and colleagues elegantly confirms the implication of mitochondria in the pathophysiology of this disease .\nof course , the importance of platelet mitochondrial dysfunction per se has to be put in perspective .\nhowever , as demonstrated previously in the pig , platelet mitochondrial dysfunction mirrors the mitochondrial dysfunction in other vital organs .\nplatelets are more easily accessible than vital organs like the liver or kidney . for research purposes in humans\nnow that serious research on this rare disease has started , we can also imagine improving its care .\ncurrently , the treatment is only supportive : increasing blood pressure with fluid infusion and catecholamines and promoting metformin elimination by renal replacement therapy . restoring atp production during energy failure due to mitochondria dysfunction is still challenging .\nanother condition associated with mitochondrial dysfunction , succinate can bypass respiratory chain complex i inhibition and restore oxygen consumption . in isolated cells\n, succinate is reputed not to cross the plasma membrane , but methyl succinate ( a cellpermeant succinate ) has been used to bypass metformin blockade of respiratory chain complex i .", "answer": "does metformin - associated lactic acidosis really exist ? despite an old controversy , there is no doubt about it . but \n do we understand what is going on ? \n laboratory findings raised several hypotheses explaining the pathophysiology of this disease . \n the main cause could be an inhibition of either gluconeogenesis or mitochondrial respiratory chain complex i. from bench to bedside , one hypothesis is now confirmed in humans . \n metformin poisoning involves , at least partially , a mitochondrial dysfunction .", "id": 620} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit negatively influences the child 's quality of life and is an important cause of absence from school and also a significant factor in health - related costs among children and adolescents .\nits prevalence varies greatly from 5.9 to 82% , depending on the definition criteria and the age of the patients .\nthe international headache society classifies headaches into primary and secondary type in classification of headache disorders 2 edition ( ichd - ii ) .\nprimary headache is not attributed to any other disorder . in the majority of patients with primary headache , general and neurological examinations are normal and\nprimary headaches include migraine , tension - type headache , cluster headache , autonomic cephalalgias and other primary headache disorders .\nfrequency of headache increases with age in this population . in the present study we aimed to determine epidemiologic characteristics and compare socioeconomic and some clinical factors related to primary headaches in children / adolescents ( 4 - 15 year olds ) presented to neurology clinics of tabriz university of medical sciences .\nthe institutional review board at tabriz university of medical sciences approved the study protocol . after obtaining a written informed consent from parents , children with 4 - 15 years of age and with the diagnosis of primary headache ( migraine or tension - type headaches ) who presented to the neurology clinics affiliated to tabriz university of medical sciences , tabriz , iran from march 2009 to october 2011 were included in this cross - sectional study .\na total of 190 patients fulfilled the criteria for enrollment in the study and their demographics were collected .\nwe noted the type of headache , history of atopy , asphyxia during labor ( according to the history of admission in the neonatal intensive care unit after birth due to respiratory problems based on the parents report and review of the previous medical records ) and breast feeding , family history of headache , presence of headache triggers and the socioeconomic status of the family .\ndiagnosis of migraine and tension - type headache was based on the international headache society diagnostic criteria for the primary headache disorders .\nsocioeconomic status was determined according to the total monthly family income ( < 7,000,000 rl vs = 7,000,000 rl ) based on the index of statistical center of iran for grand cities in the years of study in addition to the highest level of education of the father ( < or = high school vs. > or = college ) .\nstatistical analysis was conducted with spss , version 16.0 for window ( spss , chicago , il ) .\ndata were expressed as meansd for quantitative variables and as numbers and percentages for categorical variables .\nstatistical analysis was performed using the chi - square test for categorical variables and the student 's t test for numerical variables .\neighty eight patients ( 46.3% ) had migraine and 102 patients ( 53.7% ) had tension - type headache .\nthe distributions of gender and age groups in patients with migraine or tension - type headache are shown in table 1 . \n \nthe distributions of gender and age groups in patients with migraine or tension - type headache data are presented as numbers no significant differences were seen in the distribution of gender between the patients with migraine and tension - type headache .\nmigraine and tension - type headache had comparable frequency in different age groups of male patients ( p=0.1 and 0.07 , respectively ) .\nin female patients the frequencies of both migraine and tension - type headache were significantly higher in the age group of 10 - 15 years as compared to the age group of 4 - 9 years ( p=0.03 and 0.04 , respectively ) .\nthere was no significant differences regarding the prevalence of migraine or tension type headache between different genders in the same age group .\nthe most common clinical presentations of aura in patients with migraine are demonstrated in table 2 .\nthe comprehensive data regarding the epidemiologic characteristics of patients with migraine or tension - type headache in our study group are shown in table 3 . \n \nthe clinical presentations of aura in patients with migraine the characteristics compared between patients with migraine and tension - type headache as triggering factors for headache ; or : odds ratio ; ci : confidence interval history of asphyxia during labor was more prevalent among patients with migraine as compared to the tension - type headache ( p=0.007 , or = 3.24 ) . history of headache in parents was also significantly higher in patients with migraine as compared to tension - type headache ( p=0.001 , or = 3.19 ) .\nmoreover , the prevalence of atopy was significantly higher in patients with migraine ( p=0.01 , or = 5.70 ) .\nprevalence of feeding with formula during infancy did not differ between the patients with either migraine or tension - type headache ( p=0.9 ) .\nthe low socioeconomic status was more prevalent in patients with migraine headache ( p=0.003 , or = 2.38 ) .\nin our study primary headache was more common in older age group which is consistent with danold 's findings which showed that frequency of headache increases with age .\ntension type headache in patients was more frequent than migraine which is comparable with findings of kroner - herwig et al .\nthe main finding in the present study was that gender can not predict the type of primary headache in younger children , as no gender differences were seen between the patients with migraine or tension - type headache in the age group 4 - 9 years .\nthis finding is in contrast to previous report by krner - herwig et al which showed that being female was a significant predictor for three main subtypes of primary headaches\na few other studies showed that the prevalence of migraine was higher in the males .\nour results also demonstrated that the frequencies of migraine and tension - type headache were comparable in different age groups of male patients , whereas female patients in the age group 10 - 15 years had higher frequency of both types of headache especially migraine as compared to the age group 4 - 9 years .\nthis finding reveals that female adolescents had higher risk for developing primary headache specially migraine as compared to female children .\nthese results agree with those reported by krner - herwig et al who showed that children with migraine were significantly older than children in the other groups .\nit could be due to hormonal effect as the trigger of migraine headache in the female adolescents .\nit was previously shown that primary headache in children is closely related to history of headache in their parents .\nour results demonstrated that when a parent showed combined headache , the risk of developing migraine in his or her child is more conspicuous as compared to the tension - type headache .\nthis finding is consistent with previous reports by fallahzadeh et al and krner - herwig et al which showed a stronger association between family history of headache and being afflicted by migraine as compared to tension - type headache in children .\nour study also demonstrated that if the patients with history of peripartum asphyxia would develop primary headache it would more probably be of migraine type .\nthese results partly agree with those reported by maneyapanda et al who found an association between chronic migraine headache and significant perinatal insult due to neuroplasticity and its induced hyperexcitability .\nhowever , it is recommended to design prospective studies to compare the frequency of primary headache ( either migraine or tension - type headache ) in patients with or without perinatal insults to elucidate the role of peripartum asphyxia as a risk factor for developing primary headaches .\nwe also showed that atopy is more prevalent in patients with migraine as compared to tension - type headache .\nalso ozge et al found an association between atopy and both migraine and episodic tension - type headaches .\nit has been shown that alteration in several interleukins occurs in migraine which supports an association between migraine and atopic disorders .\nalthough it was shown by pogliani et al that breast feeding has a protective role against primary headache disorders , our results showed that children and adolescents with history of formula feeding during infancy have comparable prevalence of developing either migraine or tension - type headache .\nour results showed that socioeconomic status of the patients could significantly influence the frequency of migraine in comparison to tension - type headache .\nayzenberg et al in a study on 2725 adults in russia , showed that low socioeconomic status is associated with higher frequency of primary headache disorders .\nmoreover , katsarava et al in another study on 1145 adult patients in the republic of georgia showed that low socioeconomic status and female gender are risk factors for development of migraine , not tension - type headache .\nmoreover , the possible role of psychological factors and behavioral characteristics influencing primary headaches could have been considered .\nwhile some variables have been checked by the present report , further prospective studies with larger sample sizes are needed to provide more comprehensive data regarding associated factors in childhood primary headache .", "answer": "objectiveheadache is one of the most common neurologic problems in children and adolescents . \n primary headache including migraine and tension - type headache comprises the vast majority of headaches and are associated with marked incidence , prevalence , and individual and social cost . \n we aimed to assess demographic characteristics and to compare some factors related to primary headaches in children/ adolescents presented to neurology clinics of tabriz university of medical sciences.methodschildren from 4 to 15 years of age with the diagnosis of primary headache ( migraine or tension - type headaches ) who presented to the neurology clinics affiliated to tabriz university of medical sciences , tabriz , iran from march 2009 to october 2011 are included in this cross - sectional study . \n data regarding the type of headache , history of atopy , peripartum asphyxia , and breast feeding , family history of headache and the socioeconomic status of the family were collected . \n the diagnosis was based on the international headache society diagnostic criteria for the primary headache disorders.findingsone hundred ninety children ( 107 females ) with primary headache ( 88 patients with migraine and 102 patients with tension type headache ) enrolled in the study . \n peripartum asphyxia , history of atopy , family history of headache and low socioeconomic status ( ses ) were more common in patients with migraine ( p - values : 0.007 , 0.01 , 0.001 , 0.003 ; respectively).conclusionphysicians need to extent their knowledge regarding the primary headaches . \n peripartum asphyxia , history of atopy , headache in parents and low ses have been shown in the present study to be more prevalent in patients with migraine as compared to tension - type headache .", "id": 621} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nplica neuropathica is an acquired , rare condition characterized by sudden and irreversible matting of scalp hair in otherwise healthy individuals .\nit was formerly supposed to be a disease peculiar to poles ( hence named as plica polonica ) and was usually the result of neglect or parasitic infestations .\nsubsequently , other factors such as shampoos , conditioners , herbal soaps , and psychiatric morbidity were also reported to result in matting of scalp hair .\na dermatology consult was sought for a 65-year - old female who developed severe matting of scalp hair for 1 week .\nshe was admitted under medical services for the management of azathioprine ( 50 mg once daily for a month ) induced pancytopenia , which was prescribed for pulmonary sarcoidosis .\nshe gave a history of loss of hair from frontal area of scalp , that came out in bunches , followed by spontaneous tangling of hair over the top of her head to form a stiff protuberant mass [ figure 1 ] .\nshe had no features of scabies or lice and shampooed her hair once a week with a non medicated shampoo .\nthere was no history of use of any chemical treatment for her hair such as streaking or straightening of hair .\nexamination of scalp revealed diffuse non scarring loss of hair over the frontal area and a mass of solid irregular matted hair located over the vertex , approximately 10 cm in height [ figure 1 ] .\ninvestigations revealed total leucocyte count of 0.9 10/l ( reference range 4.011.0 10/l ) , hemoglobin of 7.4 g% ( reference range 1215.5 g% ) , and platelet count of 0.49 10/l ( reference range 1.54.5 10/l ) .\nexamination revealed noncicatricial hair loss over the frontal region and elongated stiff protuberant mass of matted hair on the vertex which could not be detangled .\nthe matting of hair in case 1 . also diffuse hair loss form the scalp can be appreciated a 30-year - old female was referred for the sudden loss of hair and severe tangling of hair that could not be combed for 3 days .\nher medical history was significant for the development of hydatidiform mole followed by methotrexate induced pancytopenia , severe stomatitis , and erythema multiforme over hands , feet , and upper trunk [ figure 2a ] .\nshe was on methotrexate 25 mg once a day for 5 days , two cycles given over a period of 1 month . during her hospital stay , she found difficulty in combing her hair that became extensively tangled . over next few days , she tried to comb her hair without success and found that her hair had been irreversibly matted and also the loss of hair over frontal area of scalp [ figure 2b ] .\nthere was no history of skin or hair disease in past , and she regularly shampooed her hair once or twice a week .\npertinent investigations revealed total leucocyte count of 1 10/l ( reference range 4.011.0 10/l ) , hemoglobin of 8 g% ( reference range 1215.5 g% ) , platelet count of 0.55 10/l ( reference range 1.54.5 10/l ) and peripheral blood film predominantly normocytic normochromic . on examination\n, she had extensive noncicatricial alopecia involving the middle two - third of the scalp .\nshe was managed conservatively for pancytopenia and scalp hair were shaved off as a part of treatment for plica .\na dermatology consult was sought for a 65-year - old female who developed severe matting of scalp hair for 1 week .\nshe was admitted under medical services for the management of azathioprine ( 50 mg once daily for a month ) induced pancytopenia , which was prescribed for pulmonary sarcoidosis .\nshe gave a history of loss of hair from frontal area of scalp , that came out in bunches , followed by spontaneous tangling of hair over the top of her head to form a stiff protuberant mass [ figure 1 ] .\nshe had no features of scabies or lice and shampooed her hair once a week with a non medicated shampoo .\nthere was no history of use of any chemical treatment for her hair such as streaking or straightening of hair .\nexamination of scalp revealed diffuse non scarring loss of hair over the frontal area and a mass of solid irregular matted hair located over the vertex , approximately 10 cm in height [ figure 1 ] .\ninvestigations revealed total leucocyte count of 0.9 10/l ( reference range 4.011.0 10/l ) , hemoglobin of 7.4 g% ( reference range 1215.5 g% ) , and platelet count of 0.49 10/l ( reference range 1.54.5 10/l ) .\nexamination revealed noncicatricial hair loss over the frontal region and elongated stiff protuberant mass of matted hair on the vertex which could not be detangled .\nthe matting of hair in case 1 . also diffuse hair loss form the scalp can be appreciated\na 30-year - old female was referred for the sudden loss of hair and severe tangling of hair that could not be combed for 3 days .\nher medical history was significant for the development of hydatidiform mole followed by methotrexate induced pancytopenia , severe stomatitis , and erythema multiforme over hands , feet , and upper trunk [ figure 2a ] .\nshe was on methotrexate 25 mg once a day for 5 days , two cycles given over a period of 1 month . during her hospital stay , she found difficulty in combing her hair that became extensively tangled .\nover next few days , she tried to comb her hair without success and found that her hair had been irreversibly matted and also the loss of hair over frontal area of scalp [ figure 2b ] .\nthere was no history of skin or hair disease in past , and she regularly shampooed her hair once or twice a week .\npertinent investigations revealed total leucocyte count of 1 10/l ( reference range 4.011.0 10/l ) , hemoglobin of 8 g% ( reference range 1215.5 g% ) , platelet count of 0.55 10/l ( reference range 1.54.5 10/l ) and peripheral blood film predominantly normocytic normochromic . on examination\n, she had extensive noncicatricial alopecia involving the middle two - third of the scalp .\nshe was managed conservatively for pancytopenia and scalp hair were shaved off as a part of treatment for plica .\nin 1884 , when le page first described a case of acute matting of scalp hair , he referred to it as plica neuropathica as he believed it stemmed from hysterical tendencies .\nit was prevalent in poland in the 19 century , hence was named plica polonica or polish plait .\nit presents as a compact mass of scalp hair with irregular twists and irreversibly entangled plaits which are firm to hard impenetrable mass of keratin cemented together with dirt and exudates .\nthe process of matting is essentially similar to the phenomenon of felting which occurs in wool and textile industries in which there is compacting of contiguous fibers exposed to surface damage and friction .\nit occurs when fibers are stirred together in a liquid medium and are subsequently exposed to increased functional forces .\nif the hair is rubbed along its shaft , it gets electrically charged with positive polarity if the friction is toward the root and negative if friction is toward the free end .\nprobably matting of hair does not occur either from electrostatic attractions or from liquid crystal formation but from the combination of the two .\nthe exact mechanism for matting is not well - understood but both physical and chemical factors that damage hair shafts may play a role [ figure 3 ] .\nplausible mechanisms of pathogenesis of plica neuropathica various etiologies have been propounded from time to time .\na thorough review of the available literature has led to a plethora of causes [ table 1 ] .\nthe various etiological factors of plica neuropathica temporary hair loss ( alopecia ) is a common side effect of chemotherapy .\nhair follicles ( hf ) are hair shaft - producing miniorgans showing during postnatal life a unique pattern of cyclic activity with periods of active growth ( anagen ) , relative resting ( telogen ) , and apoptosis driven involution ( catagen ) .\nhf 's are strongly affected by many chemotherapeutic agents because of the rapid proliferative rate of hair matrix keratinocytes during anagen .\nimmunosuppressive drugs commonly lead to anagen effluvium due to abrupt cessation of mitotic activity in the rapidly dividing hair matrix cells so that either no hair is produced , or a narrowed and defective hair shaft is produced and the hair loss is evident within days to weeks of drug administration .\nhowever , azathioprine is not normally known to be a cause of anagen effluvium and it is possible that the sudden pancytopenia results in hair shaft damage leading to hair loss and hair shaft cuticular damage resulting in matting of hair .\nplica neuropathica generally affects healthy persons but has been described in a 54 years and a 14-year - old chronically ill female with azathioprine - induced pancytopenia , without any history of neglect , parasitic infestation , and shampooing . on the other hand , methotrexate has not been reported to cause matting of hair though it can lead to hair fall .\nantimitotic chemotherapeutic agents such as methotrexate induce arrest of the anagen phase and present a toxic insult to the rapidly dividing hair matrix .\nhair loss usually begins 12 weeks after chemotherapy is started and is most noticeable by 12 months .\nthese antimetabolite drugs induce dystrophic changes in the new follicles as well as in the already growing hf .\nthey also lead to premature regression as a result of massive apoptosis in the entire proximal hair bulb leading to subsequent hair shedding .\nwhen functional forces are applied to the already damage cuticle of the long and old hair , proximity of shafts increases , and tangling occurs leading to plica .\nfurthermore the unfruitful efforts by the patient to comb the unruly hair lead to electrostatic attraction and increase the chances of matting of the long and old hair .\nthe chemotherapy - induced hair loss and the effects on the growing hf , and the resultant cuticular damage is much more complex than previously appreciated and may require distinct molecular studies to further collaborate these theories .\nboth of our patients agreed to the manual removal of hair as a part of treatment .\nhowever , it can still be prevented from developing by adequate hair care and washing habits .\nprevention measures that can be adopted are : \n regular cleaning of hair with mild cleansers or shampoosgentle oiling and combing to avoid entanglingregular hair trimmingavoid hair piling over vertex while washing and backcombingavoid rotatory rubbing of hairlong hair should be given a backwash or be washed in the sink . \n \nregular cleaning of hair with mild cleansers or shampoos gentle oiling and combing to avoid entangling regular hair trimming avoid hair piling over vertex while washing and backcombing avoid rotatory rubbing of hair long hair should be given a backwash or be washed in the sink .\nmatting of hair in two patients on azathioprine and in a patient on chemotherapy ( doxorubicin , cyclophosphamide and cisplatin after surgery for papillary cystadenoma ovary ) following washing of hair with a soap containing acacia concinna , have been reported previously .\nthe current report is probably only the third case of plica neuropathica associated with azathioprine - induced pancytopenia and first with methotrexate in literature and unusual in that it occurred not because of neglect and poor hair care or overzealous shampooing of hair but due to cuticular damage of hair shaft secondary to the immunosuppressive drug induced pancytopenia .\nwe consider that matting of hair is not truly a hair disorder , rather a reaction resulting from the interplay of great motley of factors . moreover , the role of myriad factors such as chronic illness , hospital stay , pancytopenia , and drug induced cuticular damage is still debatable .", "answer": "plica neuropathica also known as birds nest is irreversible matting of hair seen in otherwise healthy individuals and is usually associated with use of ionic / herbal soaps , shampoos , parasitic infestations , psychiatric alterations , or neglect . \n anagen effluvium is a known side effect of many immunosuppressive drugs . \n rarely matting of hair has been reported following azathioprine . \n we report plica neuropathica in two chronically ill patients on immunosuppressive drugs , that is , azathioprine and methotrexate along with a review of literature of its etiological factors and pathogenesis .", "id": 622} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe ministry of health , labour and welfare \n of japan has recommended shortening of the length of hospital stays1 . in general , shortening the length of stay contributes to a \n reduction in the physical and mental stress of patients and rapidly returns them to their \n jobs and communities .\nactually , in a previous study , it was shown that a shorter length of \n stay resulted in not only a financial benefit but also a patient benefit2 .\nthe patient s benefit is spending less time \n out of their home and reduction of the possibility of contracting nosocomial infections \n during a stay in the hospital2 . in stroke \n patients , stroke - related impairment , medical complications , family support , and\ndischarge \n destination predict the length of stay3 . \n in another previous study , impairment , activities of daily living ( adl ) , unplanned \n discharges , and discharge to facilities affected the length of stay4 . on the other hand ,\nsimilarly , patient - related factors were found to affect rehabilitation outcome , whereas \n illness- and intervention - related factors did not6 .\nthis behavior pattern \n includes impatience , urgency , aggressiveness , and particularity about details .\nthe type a \n behavior pattern is regarded as an independent risk factor of cardiovascular diseases7 .\nhowever , patients with type a behavior \n pattern characteristics may have better compliance with rehabilitation and other forms of \n medical and social support than those with non - type a behavior .\nif patients with the type a \n behavior pattern have better compliance , they would have a shorter length of hospital stay \n than those with non - type a behavior . to examine this hypothesis , in this study , we compared \n the length of stay of patients with the type a behavior pattern with that of patients with a \n non - type a behavior pattern .\nwe hypothesized that length of stay of patients with the type a \n behavior pattern would be shorter than that of patients with a non - type a behavior \n pattern .\nfifty - seven patients participated in this study . all patients had stayed in the \n comprehensive rehabilitation unit of omaezaki municipal hospital between april and december \n 2013 .\nthe exclusion criteria were as follows : transfer to another hospital , medical \n facility , or welfare facility during the research term and refusal to provide informed \n consent .\ntype a behavior pattern was assessed by an abbreviated set of 12 questions developed by \n maeda8 .\nhardly were scored as 2 , 1 , and 0 points , respectively , for nine \n questions , and the points were doubled for three questions .\na total score of 17 or greater \n was defined as type a , and the other subjects were defined as non - type a. after the subjects \n were discharged , we counted the number of days between admission and discharge to evaluate \n the length of stay . to evaluate the ability to perform adl at discharge , we measured barthel \n index for all patients .\nwe used the student s t - test to examine statistical differences in \n length of stay and barthel index at discharge between subjects with type a behavior and \n those without type a behavior .\nwe analyzed these measurements by statistical package for social sciences ( spss ) \n version 19 .\nultimately , 55 subjects ( 75.311.7 years old , 18 males and 37 females ) were classified into \n either the type a group ( n = 26 ) or the non - type a group ( n = 29 ) , as shown in table 1table 1.characteristics of the type a and non - type a behavior patternscharacteristicstype a groupnon - type a grouppatients ( n)2629male ( n)108female ( n)1621cause of admissionstroke ( n)810fractures ( n)1310disuse syndrome ( n)23others ( n)36values represent number of subjects . others\ncauses of admission include spinal code \n injury , spinal canal stenosis , and total knee arthroplasty .. the characteristics of subjects ( sex and cause of admission ) were similar in \n the two groups .\nage was not significantly different between the two groups . also , the \n barthel index at discharge was not significantly different between the two groups .\nhowever , \n length of stay was significantly higher in the non - type a group compared with the type a \n group ( p < 0.05 ) ( table 2table 2.difference in length of stay between the type a group and non - type a \n groupscharacteristicstype a groupnon - type a groupage ( years)77.271.4discharge bi97.5897.08length of stay ( days)66.287.4 * * p < 0.05 vs. type a group , values represent averages .\nothers causes of admission include spinal code \n injury , spinal canal stenosis , and total knee arthroplasty .\nour results support the hypothesis that patients with the type a behavior pattern have \n better compliance with forms of medical support than patients with a non - type a behavior \n pattern .\npatients with the type a behavior pattern had a shorter length of hospital stay \n than patients with a non - type a behavior pattern . length of hospital stay can be affected by multiple factors , including medical \n complication , family support , discharge destination3 , impairment , adl4 , \n and rehabilitation9 .\npatient - related \n factors5 , especially psychological \n factors6 , affect rehabilitation \n outcomes .\nthe subjects in this study were patients who stayed in a comprehensive \n rehabilitation unit .\npatients who stay in a comprehensive rehabilitation unit do not require \n much medical care and are able to focus on rehabilitation .\nhence , our data suggest that \n psychological factors of the patients , such as type a behavior , affect rehabilitation \n compliance .\nlength of stay , ability to perform adl at discharge , and patient age influence \n rehabilitation outcome and whether patients can return home or not10 , 11 .\nthere was no significant difference in \n barthel index or patient age between patients with the type a behavior pattern and those \n with a non - type a behavior pattern .\nthus , it appears likely that ability to perform adl at \n discharge , patient age , and destination at discharge do not influence length of stay .\nthe type a behavior pattern includes impatience , urgency , aggressiveness , and particularity \n about details .\npatients who have higher levels of physical activity during rehabilitation \n were associated with a shorter length of stay12 . because patients with the type a behavior pattern might have good \n compliance with rehabilitation and increase their physical activity\nthe type a behavior pattern is well known to be an independent \n risk factor of cardiovascular diseases7 . \n also in the japanese , the type a behavior pattern is associated with an increased risk of \n acute myocardial infarction , especially in women13 .\nso , the type a behavior pattern may be considered not a good \n characteristics in general .\nin contrast , another article reported that the type a behavior \n pattern reduced the risk of coronary heart diseases in japanese men14 .\njapanese men who do not express their anger may have an \n increased risk of high blood pressure15 . \n\nthis previous article indicates that non - type a japanese men may have a higher hypertension \n risk than type a japanese men . in the japanese , the type\nour results also show that patients with the type a \n behavior pattern may be able to return home early .\nfinally , the cause of a short length of stay may not \n be rehabilitation compliance .\nin conclusion , our results suggest that the type a behavior pattern shortens the length of \n hospital stay .\nthe data show that we should consider the patient s characteristics in \n rehabilitation to protect the patient and for financial benefit .", "answer": "[ purpose ] the aim of this study was to describe the importance of patient - related factors \n in rehabilitation . \n we focused on the type a behavior pattern . \n if individuals with the type \n a behavior pattern have better compliance , they would have a shorter length of hospital \n stay than those with non - type a behavior . \n we compared the length of stay of patients with \n the type a behavior pattern with that of patients with a non - type a behavior pattern . \n \n [ subjects and methods ] fifty - seven patients staying in a comprehensive rehabilitation unit \n participated in this study . \n type a behavior pattern , length of stay , and barthel index \n were assessed . \n we use the student s t - test to examine the statistical differences in \n length of stay and barthel index at discharge between subjects with type a behavior and \n those without type a behavior . \n [ results ] age and barthel index at discharge were not \n significantly different between the two groups . however , length of stay was significantly \n higher in the non - type a group compared with the type a group . \n [ conclusion ] patients with \n the type a behavior pattern had a shorter length of hospital stay than patients with a \n non - type a behavior pattern . in conclusion \n , our results suggest that the type a behavior \n pattern shortens the length of hospital stay . \n those data show that we should consider the \n patient s characteristics in rehabilitation to protect the patient and for financial \n benefit .", "id": 623} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsodium valproate is a frequently used drug for the treatment of seizure disorders , bipolar disease and chronic pain .\nit is known to cause a serious complication , hyperammonemic encephalopathy which is characterized by acute onset of impaired consciousness , headache , vomiting , seizures , ataxia , generalized slowing on electroencephalography and rapid recovery after discontinuation . in this submission , we present a case of valproate - induced hyperammonemic encephalopathy where the major manifestation was restricted to bilateral cerebellar clinical features .\na 19-year - old male presented with acute onset tremulousness , staggering gait and difficulty in walking and speech .\nhe was a known case of idiopathic generalized epilepsy treated initially with carbamazepine ( 800 mg / day ) and recently switched over to sodium valproate ( 1000 mg / day ) before the onset of this acute complication .\nthe patient showed bilateral cerebellar signs in the form of defective coordination in both upper and lower limbs with severe degree of gait ataxia and scanning speech .\ninvestigations including hemogram , liver function tests , renal function parameters , serum electrolytes and blood sugar showed normal results .\nthyroid function tests ( t3 , t4 , thyroid stimulating hormone ) and nutritional parameters including vitamin b12 levels were also found in normal range . however , serum ammonia level was raised to 106 mol / l ( normal range 12 - 47 mol / l ) .\nthe levels of serum valproate and carbamazepine were found to be in the normal range ( serum valproate : 52 ug / ml [ range : 50 to 100 gm / ml ] and serum carbamazepine < 1.25 gm / ml [ range : 4 to 12 gm / ml ] ) .\npatient underwent magnetic resonance imaging of cranium , which turned out to be normal . with this background of clinical observations and laboratory assessment , a diagnosis of valproate - induced hyperammonemic encephalopathy\nthe valproate was replaced by levetiracetam ( 500 mg ) two times a day along with carnitine supplementation .\nthe patient showed rapid recovery and was able to walk without support after a week .\nhis serum ammonia level normalized on repeat serum ammonia estimation ( 20 mol / l ) .\nvalproic acid by virtue of its broad spectrum of action has application in various disorders like epilepsy , bipolar disorders , prophylaxis and treatment of migraine and neuropathic pain .\nalthough valproate - induced hepatic dysfunction leading to encephalopathy is a well - recognized entity , less commonly the drug can also produce an encephalopathy of non - hepatic origin by producing hyperammonemia , and is called as valproate - induced non - hepatic hyperammonemic encephalopathy ( vnhe ) .\nother causes of non - hepatic hyperammonemia include inborn errors of metabolism ( urea cycle enzyme defects , fatty acid oxidation defects ) , drugs like 5-fu , asparaginase , salicylate , halothane and enflurane , hematologic diseases like multiple myeloma and acute myeloblastic leukemia , hyperinsulinemia , hyperglycemia , distal renal tubular acidosis , parenteral nutrition and reye 's syndrome .\nthe clinical presentation of hyperammonemic encephalopathy constitutes irritability , drowsiness , coma and occasionally these patients have paradoxical seizures .\nthe presence of significant hyperammonemia with cerebellar signs and reversal of hyperammonemia , encephalopathy and disappearance of cerebellar signs and symptoms after discontinuation of sodium valproate confirmed the diagnosis of valproate - induced hyperammonemic cerebellar ataxia with metabolic encephalopathy .\nthis view is also supported by generalized slowing in eeg suggestive of metabolic encephalopathy which also normalized after discontinuation of valproate .\nwe estimated serum valproate and carbamazepine levels which were within normal limits although there is little correlation between valproate level and clinical effects because of the variable absorption rate and short half - life of the drug .\nin our study , there was decline in ammonia levels after withdrawal of valproate and subsequent disappearance of cerebellar symptoms and features of encephalopathy .\nthere is scarcity of literature on unusual symptoms of valproate - induced hyperammonemic encephalopathy presenting as mainly cerebellar ataxia .\ncases have been reported where patients presented with acute onset of confusion , decline in cognitive abilities , and ataxia .\nwe gave carnitine supplementation to our patient as valproate is known to enhance urinary excretion of l - carnitine , leading to depletion of its blood stores .\nthus we conclude that valproate - induced hyperammonemic encephalopathy can present mainly with cerebellar ataxia and a high index of suspicion is required for an early recognition , investigation , and treatment of this potentially life - threatening condition .", "answer": "valproate - induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium , vomiting , headache , seizures and focal neurological deficits . \n the pathogenesis of this dreadful complication is not well understood , although hyperammonemia has been implicated in causation of encephalopathy . in this submission , we have highlighted a case of valproate - induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram . \n high index of suspicion of valproate - induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder .", "id": 624} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfitz hugh curtis syndrome is an extra - pelvic manifestation of pelvic inflammatory disease ( pid ) and is characterized by perihepatic adhesions between liver capsule and diaphragm or anterior peritoneal surface(13 ) .\nmost fitz hugh curtis syndrome patients are women of child bearing age and rarely has the syndrome been reported in males .\nthe predominant symptom is pain in the right upper quadrant , which may be confused with biliary disease\nan abdominal computed tomography ( ct ) scan may reveal subcapsular enhancement of the liver in arterial phase ( 4 ) . we herein report a case of fitz hugh curtis syndrome in a male patient that was diagnosed via laparoscopy .\na 29 year - old african american male with russel - silver dwarfism presented with one day history of diarrhea , nausea , vomiting , right side abdominal pain , and abdominal distention .\nthe pain was constant , gradually increasing in severity , and not related to food intake .\nhis medical history was significant for russel - silver dwarfism , calcium deficiency , cardiomegaly , and bilateral testicular implants for undescended testicles .\nthe patient was sexually active only with his girlfriend and denied any history of sexually transmitted disease . on examination patient was afebrile and his vitals were stable .\nlaboratory workup revealed white blood cell ( wbc ) count of 14,000/l with normal liver function tests .\nct scan of the abdomen and pelvis showed a small amount of free fluid in pelvis ; the proximal appendix appeared normal , however the distal appendix was not visualized .\nthe liver capsule appeared normal and there was no subcapsular fluid collection ( figure 1 ) .\nct scan showing normal appearing liver capsule and no perihepatic fluid collection the patient was admitted to the surgical service .\nhe was made nil per os ( npo ) , and placed on intravenous fluids and pain medication .\nhe was refusing any surgical intervention at this point . on hospital day 5 , a repeat abdominal ct scan demonstrated a normal appearing liver , small bowel , large bowel , and appendix , with a mild increase in pelvic free fluid .\nas the patient 's symptoms did not improve with conservative management , he ultimately agreed to undergo a diagnostic laparoscopy , and was taken to the operating room on hospital day 9 .\nthe small bowel was run in a retrograde fashion starting at the caecum , and no stricture , mass , or perforation was noticed .\nappendectomy was not performed as per patient'swishes . following the procedure , the patient reported complete resolution of his symptoms .\nhis diet was gradually advanced , which he tolerated well , and was discharged on post operative day 2 .\nfitz -hugh curtis syndrome was first described in 1920 by carlos stajano . in the 1930 's thomas fitz \nhugh and arthur curtis also described the syndrome and made a connection between right upper quadrant pain following a pelvic infection and violin string like perihepatic adhesions(5 ) . the first case of gonococcal perihepatitis in a male\nthe incidence ranges from 4% to 14% in women with pid , but is as high as 27% in adolescents with pid , whose less mature genitourinary tract anatomy makes them more susceptible to infection(1 ) .\nthe inflammation of the liver capsule has been attributed to the direct bacterial spread from an infected fallopian tube via the right paracolic gutter . in men , hematogenous and lymphatic spread to liver\nthe predominant symptoms are right upper quadrant pain , tenderness , and pleuritic right sided chest pain(2 ) .\nthese symptoms can pose diagnostic challenges as they may be confused with biliary tract symptoms . in a clinical setting ,\nthe diagnosis is adequately established by excluding other possible causes of right upper quadrant pain . on laboratory examination ,\nwhite blood cell count can be elevated in nearly half of the patients , while liver function tests are normal in most patients . because urethral cultures frequently fail to demonstrate the presence of gonorrhea and chlamydia , the serologic microimmunofluorescence antibody test is helpful in diagnosis ( 2 ) .\nct scan may show subcapsular fluid collection , thickening of hepatic capsule in the arterial phase , and wedging enhancement of the involved liver parenchyma in more than 50% of patients .\nmost cases of fitz hugh curtis syndrome are managed with antibiotics against gonorrhea and chlamydia .\nit occurs mostly in premenopausal women , however , cases in males have also been reported .", "answer": "fitz hugh curtis syndrome is a condition characterized by inflammation of the liver capsule with concomitant pelvic inflammation without involvement of liver parenchyma . \n it is classically seen in young women who present with sharp , pleuritic right upper quadrant pain , usually but not always accompanied by symptoms of pelvic inflammatory disease ( pid ) and is frequently confused with biliary tract disease . rarely the syndrome has been reported in males , hematogenous and lymphatic spread to liver is thought to be the underlying mechanism . \n serological tests and computed tomography ( ct ) scan may aid in diagnosis of fitz hugh curtis syndrome . \n definitive diagnosis is made by laparoscopy , which provides both diagnostic and therapeutic benefits . \n we report a case of fitz hugh curtis syndrome in a young male patient , which was diagnosed and treated by laparoscopy . \n we also include a review of the literature .", "id": 625} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npsychobehavioral approaches attempt to identify the underlying cognitive dissonance creating the intense emotional discomfort that can trigger seizures .\na recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of seizure self - control .\nthis case report illustrates how a psychobehavioral intervention addresses cognitive dissonance in order to decrease internal stressors of seizures and was prepared according to the consensus - based care guidelines for standardized clinical case reporting .\nhis magnetic resonance imaging ( mri ) shows extensive bilateral gray matter band heterotopia ( fig . 1 ) .\nelectroclinical day- and nighttime seizures captured during video - eeg studies displayed seizures with loss of consciousness consisting of irregular shaking of his body correlating with epileptiform activity originating from bilateral parasaggital regions synchronously and tonic posturing of arms originating from the left hemisphere . before losing consciousness , he feels a loss of sensation in some of his body parts , usually starting from his right arm .\nthese findings suggest localization - related epilepsy originating from the left hemisphere and bilateral parasagittal regions with simple and complex partial as well as secondarily generalized seizures .\nhe experiences predominantly nocturnal seizures that occur in clusters of up to four complex partial seizures once or twice per week and daytime seizures once or twice per month .\na. 's parents had installed an acoustic monitoring device in his bedroom and reported that this baseline seizure frequency had remained unchanged for > 3 years prior to the beginning of the intervention .\na. is currently taking valproate , topiramate , and lamotrigine and complies with the modified atkins diet protocol .\npast medication failures have included carbamazepine , levetiracetam , clobazam , and oxcarbazepine . during previous psychological assessments\n, he has been diagnosed with a verbal and auditory learning disability as well as expressive language impairment . because of parental worries that challenges would increase a. 's seizure frequency , a. received parental support for doing his schoolwork , and he was never expected to contribute to household chores . as a result\n, a. was deprived of opportunities to build his confidence in his own achievements and pictures himself as broken \notherwise , a. is in good health ; he has never used alcohol or tobacco .\na. and his parents consented to the use of these data for this case report .\nto resolve the resultant conflict between insecurity with his performance , fear of failure , and high expectations of himself , a. actively avoided responsibility and demanded help rather than engaging in self - reliant problem - solving behaviors .\nthis defense mechanism that incorporated learned helplessness and secondary gain issues was exacerbated by an anticipated challenge at school or social anxiety .\nafter an initial assessment period comprising two sessions of 3 h each , a treatment plan was formulated including the workbook taking control of your epilepsy , daily journaling , and daily relaxation exercises .\nthe participant received training in abdominal breathing and visualization techniques ( imaginary journey and an attention - focusing exercise ) to address early seizure warning symptoms .\nthe initial assessment was followed by weekly counseling sessions of 1030 min that were conducted over the phone for 12 months , and monthly sessions were conducted for a 6-month follow - up period .\na. engaged in a daily guided relaxation practice after returning from school and listened to a nonguided relaxation tape before going to bed .\nhe reports that he is able to interrupt warning signs of the early onset of a seizure by utilizing deep diaphragmatic breathing , visualization techniques , and self - affirmation statements of personal choice ( e.g. , peace and release ) .\na. 's parents report that he took on responsibility for the completion of his schoolwork and studies in a self - motivated and timely fashion , all of which helped him to prevent the buildup of anxiety . after a nighttime seizure\n, he can reliably identify the behavioral strategy which he could have employed in order to avoid the buildup of distress during the day prior to the seizure .\na. admitted that it was , at times , easier to have a seizure rather than to address the situational accumulation of seizure triggers by taking responsibility and implementing the appropriate proactive behaviors .\nhence , motivational exercises were employed to allow a. to deliberately weigh the motivational factors and obstacles regarding prior set goals ( e.g. , an early bed rest ) to facilitate informed changes of his present decision - making habits . while he considered himself broken at the beginning of the intervention , he has developed a perspective on life in which he feels that he can shape his future according to his preferences if he follows through with taking responsibility for the acquisition of self - organizational skills ( see patient perspective in table 1 ) . by the end of the follow - up period\nhis nighttime seizures dropped to 12 clusters per month after 6 months of participating in the intervention .\nsince the internalization of the therapeutic principles is an active process that requires continuous learning , motivation , and compliance of the individual , effects are usually expected 36 months after the beginning of the intervention , especially since it takes an individual at least 12 weeks to finish the 12 sessions of the workbook .\nthis seizure frequency has remained stable during the remaining 6 months of the intervention and the 6-month follow - up period ( fig . \n( 3 months after the follow - up period ) , the seizure frequency has still remained the same despite increasing stressors that arise within the framework of a. 's successful admission to college .\nthe implementation of the therapeutic strategies correlated with a cessation of daytime seizures and a clinically significant drop of nighttime seizures .\nliterature suggests that seizure frequency may be positively influenced by the restoration of balance within the autonomic nervous system by the regular practice of relaxation exercises and proactive avoidance of emotional distress during wakefulness , thereby preventing the buildup of seizure activity .\nfurthermore , a. would regularly wake up during the night when preictal or early ictal phenomena arose ; he would then react with the application of previously practiced countermeasures .\nliterature indicates that evidence for the enhancement of psychological well - being by psychobehavioral therapy is more established , while reliable evidence on its role on seizure control is scarce .\nthe a / r intervention may represent the most comprehensively developed cognitive behavioral approach to epilepsy that has repeatedly been correlated with a reduction of seizure frequency in individuals with complex partial seizure disorders in uncontrolled prospective and retrospective studies , , .\nthe possibility of false negative self - reports of seizure occurrence can not be ruled out but seems unlikely because the patient and his parents have been very conscientious in keeping a seizure diary for a long time .\nbecause of the uncontrolled nature of a case report , nonspecific effects of attention and natural fluctuations of seizure frequency that could have contributed to improve seizure frequency can not be factored into the interpretation of the presented data .\nhowever , the long and stable seizure frequency prior to the intervention makes natural fluctuations unlikely .\nfurthermore , the decreased seizure frequency has remained stable during follow - up and post follow - up with decreased and no contact with the a / r counselor which makes unspecific effects of attention implausible .\nin this case of a 16-year - old male , the acquisition of self - organizational skills and the development of seizure interruption techniques correlated with a clinically significant drop of seizures and an increased sense of being in control of his seizures . the case exemplifies that motivational strategies may be applied to facilitate the regulation of lifestyle - related seizure precipitants .\nfuture prospective studies are needed to further investigate the psychological mediators of an individual 's increasing sense of seizure self - control and its actual relationship with seizure frequency .", "answer": "a recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of psychobehavioral interventions for epilepsy that address the bidirectional relationship between psychological states and seizures . \n the report was prepared according to the consensus - based care guidelines for standardized clinical case reporting.this is a case of a 16-year - old male individual with a diagnosed seizure disorder and learning disability who continued to have daytime and nighttime seizures on a regular basis despite exhausting of available conventional treatment options . \n a psychological assessment led to the working hypothesis that cognitive dissonance between fear of failure and high expectations of self had led to a broken self - image and active avoidance of responsibility that resulted in intense emotional distress which correlated with the occurrence of seizures . \n this working hypothesis resulted in a treatment plan that employed the acquisition of self - organizational skills and relaxation techniques as the main therapeutic strategy . \n motivational strategies were employed to facilitate the regulation of lifestyle - related seizure precipitants . in this case , the acquisition of self - organizational skills and the development of seizure interruption techniques correlated with a clinically significant decrease of seizures . \n methodological limitations of the interpretation of the presented data are discussed .", "id": 626} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 9-month - old , 10-kg girl without any relevant medical history was presented at our emergency room because she had aspirated a peanut 5 hours previously .\nchest computed tomography showed a foreign body at the carina and the proximal right main bronchus , and emphysema in both lung fields ( fig .\nanesthesia was induced intravenously with thiopental 60 mg and rocuronium 6 mg after administering atropine 0.2 mg .\napproximately 25 minutes after the start of the operation , spo2 gradually decreased to 78% from 100% .\naccordingly , the surgeon was asked to stop the procedure , and an uncuffed endotracheal tube ( i d 4.0 , euromedical , denmark ) was intubated and fixed at 10 cm .\nleft lung sounds were heard clearly , but no right lung sounds were evident on auscultation .\nspo2 did not improve despite manual ventilation with 100% o2 and an increased inspiratory pressure airway was detected .\naccordingly , a simple chest radiograph was taken . while waiting for the result of the chest radiograph , the otolaryngologist extubated the endotracheal tube and attempted to re - insert the rigid bronchoscope in order to check for possible causes of the airway obstruction , such as , residual foreign body .\nmeanwhile , the heart rate decreased to 50 beats / min , and spo2 decreased to 57% ( blood pressure was not measured ) .\natropine 0.2 mg and epinephrine 1 g were injected intravenously , but vital signs did not improve and no carotid artery pulse was palpable . external cardiac compression was performed and epinephrine 10 g was injected intravenously three times .\nheart rate and blood pressure then recovered , and thus , cardiac compression was stopped .\na chest tube was immediately inserted into the right thorax and a massive air leak was observed . at this time\n, the sounds of both lungs were clearly heard and spo2 improved to 100% . follow up chest radiography showed a significant reduction of the right tension pneumothorax and a scattering of subcutaneous emphysema at the left upper chest and around the neck ( fig .\nthe tension pneumothorax suggested major tracheobronchial injury and a subsequent bronchoscopic examination revealed three major sites of laceration , one in the mid trachea of length 1.5 cm , a second in the distal trachea of length 2 cm ( immediately above the carina ) ( fig .\n4 ) , and a third in the right main bronchus of length 1 cm .\nan arterial line was placed in the left radial artery to monitor blood pressure continuously .\narterial blood gas analysis showed ; ph 7.10 , paco2 63 mmhg , pao2 77 mmhg , hco3 19.6\nmmol / l at fio2 1.0 , etco2 24 mmhg , and spo2 100% . after a rigid bronchoscope examination confirmed the absence of remaining foreign body , an uncuffed i d 4.5 endotracheal tube was inserted into the left main bronchus for single lung ventilation under fiberoptic bronchoscopic guidance .\nhowever , the patient did not tolerate single lung ventilation well and her spo2 decreased to 79% . in view of the facilitation of surgical approach and the risks of hypoxemia and hypoventilation ,\nafter 1,000 units of heparin was injected as a bolus , a 10 fr catheter ( fem - flex ii femoral cannula , edwards lifesciences , irvine , ca , usa ) was placed in the right internal jugular vein for drainage , and a 12 fr catheter was placed in the right femoral vein for perfusion using a sono - guided seldinger technique ( fig . 5 ) .\necmo flow was maintained at 0.7 - 0.8 l / min , and spo2 remained at 98 - 100% without mechanical ventilation . at the initiation of ecmo ,\nanesthesia was maintained with continuous intravenous infusions of sufentanil 5 g / kg / h , midazolam 0.1 mg / kg / h , and vecuronium 0.1 mg / kg / h during ecmo .\ndopamine was infused at 5 g / kg / min and vital signs were stabilized . an activated clotting time ( act ) of approximately 200 seconds\nwas maintained and arterial blood gas analysis under maximal ecmo support showed ; ph 7.34 , paco2 41 mmhg , pao2 81 mmhg , and hco3 22.1 mmol / l at fio2 1.0 .\nwhen the ecmo flow rate reduced , it was recovered by pulling the cannula in the internal jugular vein slightly .\nbody temperature , measured using an oral thermometer , fell to as low as 35.0 after ecmo was initiated , and thus , a forced air warmer was applied to prevent further hypothermia .\ntotal anesthesia time was 8 hr 25 min , estimated blood loss was 300 ml , and urine output was 120 ml ; 250 ml of crystalloid solution and 1 unit of packed red blood cells were administered .\necmo was maintained postoperatively to minimize airway pressure . in the intensive care unit ( icu )\n, the mechanical ventilation was performed using pressure control mode ( inspiratory airway pressure 10 cmh2o , pressure support 11 cmh2o , respiratory rate 20/min , fio2 0.5 and peep 3 cmh2o ) , which resulted in the expiratory tidal volume of 49 ml .\nvital signs were stable in the icu , and the patient awoke with no signs of respiratory or neurologic deficit on the first postoperative day .\nthe simple chest radiograph taken in the icu showed reduced subcutaneous emphysema and no residual pneumothorax .\nventilating bronchoscopy has the risk of severe complications , such as , infection , laryngeal edema , laryngospasm , bronchospasm , bleeding , hypoxia , pneumomediastinum , and pneumothorax .\nrothmann and boeckman reported that the probability of pneumothorax during rigid bronchoscopy for the removal of a foreign body is approximately 1% .\ntherefore , the possibility of pneumothorax should be suspected when ventilation worsens during ventilating bronchoscopy . however , an early diagnosis of pneumothorax during anesthesia is not easy because the symptom is masked by anesthesia .\ntension pneumothorax during surgery may manifest as a reduction in oxygen saturation , a rapid increase in airway pressure , hypotension , and/or tachycardia . in this case ,\nthe reasons for the delayed diagnosis in the present case were that the reduction in oxygen saturation and the diminished right lung sounds were mistakenly attributed to airway obstruction by a foreign body .\nin addition , if lung sounds had been checked more carefully , it might have been easier to determine whether the respiratory failure was due to foreign body obstruction or tension pneumothorax .\nfurthermore , it would have been safer to evaluate airway with a fiberoptic bronchoscope inserted through the endotracheal tube under ventilation rather than attempt airway assessment using a ventilating bronchoscope after extubation . during surgery on the trachea and bronchus , a double lumen endotracheal tube or\nhowever , in small children , because conventional single lung ventilation methods are likely to fail to maintain adequate ventilation and oxygenation , the elective application of ecmo may be a good option .\necmo was also useful during the postoperative course in the described case because it can minimize inspiratory airway pressure during mechanical ventilation . during ecmo\n, heparin was administered as a single bolus of 100 unit / kg followed by continuous intravenous infusion at 20 - 60 unit / kg / min .\nanticoagulation was accomplished by titrating heparin administration to maintain an act of between 180 and 220 seconds .\nfurthermore , levels of blood anticoagulation were monitored hourly , and the amount of heparin administered was carefully controlled to prevent bleeding complications .\nin addition , because the ecmo machine was not equipped with a sevoflurane vaporizer and almost no mechanical ventilation was performed during ecmo , intravenous opioids and midazolam were added for anesthesia .\nsummarizing , the tension pneumothorax should be considered when inspiratory pressure is increased and oxygen saturation is decreased during ventilating bronchoscopy .\neffective communication between the operator and anesthesiologist is essential when unexpected complications are encountered to facilitate the prompt planning of coping strategies .", "answer": "tension pneumothorax during ventilating bronchoscopy for foreign body removal is a rare but life - threatening complication . \n the authors present a case of cardiac arrest caused by tension pneumothorax in a 9-month - old girl who underwent ventilating bronchoscopy for foreign body ( peanut ) removal . \n tension pneumothorax was due to tracheobronchial lacerations caused by a bronchoscope . \n the patient was successfully resuscitated by cardiopulmonary resuscitation and chest tube insertion . \n the airway injury was effectively repaired by thoracotomy under extracorporeal membrane oxygenation .", "id": 627} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nduring october 2009october 2010 , a total of 448 respiratory specimens were obtained from 448 patients ( 258 male patients and 190 female patients ) with rtis and fevers in a virus surveillance system in osaka , japan ( 9 ) . the mean sd age of the patients was 41.4 53.7 months ( range < 1404 months ) , and 351 ( 78.3% ) were < 5 years of age .\nprocedures for viral nucleic acid extraction and cdna synthesis have been reported ( 9 ) .\npcr for detecting hrv and enterovirus was conducted by using evp4 and ol68 - 1 primers , which detected hrv and human enterovirus , respectively , in amplicons of 530 and 650 bp , respectively ( 7 ) .\nresults showed 178 positive specimens ( 140 for hrv , 16 for human enterovirus , 7 for hrv and human enterovirus , and 15 for an unexpected amplicon of 600 bp ) . to identify the 600-bp amplicon , we sequenced viral protein 4 ( vp4 ) and vp1 genes .\nblast analysis ( www.ncbi.nlm.nih.gov/ ) showed that these isolates had high identity with ev68 vp4 ( 98.5%99.5% with the pav25426868 strain [ genbank accession no\n. hm370293 ] ) and vp1 ( 96.7%97.5% with the md021 strain [ genbank accession no\nphylogenetic analysis using vp1 sequences ( 14 of 15 osaka strains were sequenced ) demonstrated that osaka strains were clustered in 1 group and differed from previously reported strains ( figure 2 ) .\nmonthly distribution of enterovirus 68 ( ev68 ) in osaka , japan , october 2009october 2010 , bars indicate no .\nphylogenetic tree of enterovirus 68 viral protein 1 gene sequences constructed by using a 927-nt sequence corresponding to nt sequence 23553281 in strain 3799 , osaka , japan , october 2009october 2010 .\ngenbank accession numbers for strains used in this analysis were fermon , ay426531 ; 3799 , ef107098 ; jpoc10200 , ab601872 ; jpoc10290 , ab601882 ; jpoc10373 , ab601873 ; jpoc10378 , ab601883 ; jpoc10396 , ab601884 ; jpoc10402 , ab601874 ; jpoc10404 , ab601885 ; jpoc10412 , ab601875 ; jpoc10441 , ab601876 ; jpoc10445 , ab601877 ; jpoc10471 , ab601878 ; jpoc10573 , ab601879 ; jpoc10616 , ab601880 ; jpoc10618 , ab601881 ; md021 , ay426491 ; tx021 , ay426495 ; mo00 , ay426493 ; wi00 , ay426494 ; mn98 , ay426497 ; tx99 , ay426498 ; md99 , ay426499 ; tx03 , ay426500 ; mn89 , ay426489 ; ny93 , ay426490 ; ev70 , d00820 ; and ev94 , dq916376\nnucleotide and amino acid identities among 4 osaka ev68 ( jpoc10 - 290 , 378 , 396 , and 404 strains ; nt 5017265 corresponding to the 3799 strain ) , fermon , and 3799 strains were determined . to determine sequences , we synthesized cdna by using specific primers and amplified 4 segments ( nt 1601153 , 5433391 , 31324032 , and 37477333 corresponding to the 3799 strain ) .\nthe fermon and 3799 strains are the only ev68 strains for which complete genome sequences are available .\nthe 3799 strain was isolated from a 6-year - old girl with pneumonia in 1998 ( h. norder , pers .\nthe sequenced region coded partial 5 untranslated regions ( utrs ) and all structural and nonstructural viral proteins ( vp43d ) .\nidentities between strains were calculated by using bioedit version 7.09 ( www.mbio.ncsu.edu/bioedit/bioedit.html ) ( table 2 ) . *\nosaka strains , jpoc10 - 290 , jpoc10 - 378 , jpoc10 - 396 , and jpoc10 - 404 ; vp , viral protein . among osaka strains ,\nnucleotide and amino acid sequences were highly conserved ( nt identity 96.5%100% and aa identity 98.6%100% ) .\nin contrast , osaka strains had lower similarities with the fermon strain ( nt identity 83.5%91.7% and aa identity 90.6%100% ) than with the 3799 strain ( nt identity 91.9%98.4% and aa identity 95.4%100% ) . when we compared individual viral proteins in osaka strains with those in the fermon strain , no gene except for vp4 showed > 90% nt sequence identity ; gene 2b showed the lowest identity ( 83.5%85.8% ) .\nregarding amino acids , < 95% identity was observed in vp1 , vp2 , and vp3 in the fermon strain , and no genes with < 95% aa identity were found in the 3799 strain in contrast with osaka strains .\nmoreover , no integration or deletion of nucleotides was observed in vp43d sequences among osaka , fermon , and 3799 strains . to clarify why ev68 osaka strain genomes were smaller than those of other enteroviruses and the ev68 fermon strain ( 7 ) , we aligned the partial 5 utr sequences ( nt 541820 corresponding to the fermon strain ) of 4 osaka , fermon , and 3799 strains ( figure a1 ) .\nresults showed that the osaka and 3799 strains had deletions at nt 681704 and 717727 in contrast with the fermon strain .\nmoreover , a 1-nt deletion in osaka strains was identified at nt 641 in contrast with the fermon and 3799 strains .\nbecause 14 patients with ev68 were detected during 20062009 ( 8) , detection of 15 patients with ev68 during a 4-month period suggests an ev68 epidemic in the summer of 2010 in japan .\nphylogenetic analysis with vp1 sequences showed that osaka strains differed genetically from previously reported strains . for precise analysis of osaka , fermon , and 3799 strains ,\nresults showed that osaka strains more closely resembled the 3799 strain than the fermon strain .\nalignment of partial 5 utr sequences showed that osaka and 3799 strains had deletions in 2 regions in contrast with the fermon strain , and the amplicon was shorter than expected .\nthe 5 utr of enterovirus contains an internal ribosome entry site ( 10 ) that is associated with translational efficiency and virulence of the enterovirus ( 11,12 ) .\ndeleted regions of osaka strains appear to be in the flanking region between the internal ribosome entry site and an open reading frame ( 1 ) .\ndetection of ev68 in numerous patients was reported in france during 2008 ( 4 ) and italy during 20082009 ( 13 ) . because this deletion was found in the 3799 strain in 1998 , recent detection of ev68 in japan\nreported that serum samples from 281 pregnant women in finland in 1983 , 1993 , and 2002 had high titers of neutralizing antibody against ev68 ( 14 ) .\nall ev68-positive patients in this study were < 5 years of age and had lower respiratory tract inflammation .\nseroepidemiologic studies in finland showed that most adults might have been previously infected with ev68 and therefore might have neutralizing antibodies ( 14 ) . increased detection of ev68 , especially in infants and children\nthis result indicates that ev68 can replicate in blood and may damage the central nervous system .\nev68 was detected in cerebrospinal fluid of a young adult patient with acute flaccid paralysis ( 5 ) .\nepidemiologic data for ev68 are lacking , and little information is available regarding virologic characteristics .\nif one considers results of phylogenetic analyses and nucleotide and amino acid identities , evolutionary changes might have occurred in ev68 .\nour results show the potential role of ev68 infection in infants and children with rtis .", "answer": "enterovirus 68 strains were detected in 14 specimens from children with respiratory tract infections and 1 specimen from a child with febrile convulsions during 2010 in osaka , japan . \n these strains had deletions in the 5 untranslated region and were genetically different from reported strains . \n this virus is associated with respiratory tract infections in japan .", "id": 628} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nThiopeptide Pyridine Synthase TbtD Catalyzes an Intermolecular Formal Aza-Diels-Alder Reaction\n\nPaper sections:\n\nThe Diels-Alder (DA) reaction has been a staple of organic synthesis since its discovery by Otto Diels and Kurt Alder in 1928.1 Numerous total syntheses have exploited different versions of this typically concerted cycloaddition reaction and related transformations to efficiently construct carbon frameworks and stitch together complex organic scaffolds.2 In recent years, it has become apparent that similar chemistry is employed widely in the biosynthetic pathways of complex natural products.3\u20136 Several enzymes have been found to catalyze DA or DA-like reactions, including PyrI4 in pyroindomycin biosynthesis, SpnF in spinosyn biosynthesis, and LovB in lovastatin biosynthesis, among others.7\u201311 In many of these cases, the enzymes work to activate, accelerate, and/or direct the stereochemical outcome of an otherwise spontaneous cycloaddition reaction. As a result, reactions catalyzed by these Diels-Alderases can be highly substrate dependent and their biocatalytic utility is limited.
Pyridine synthases in thiopeptide biosynthesis provide unique examples of what is thought to be an enzyme catalyzed aza-DA. The biosyntheses of thiopeptides are similar to other ribosomally synthesized and post-translationally modified peptides (RiPPs) in that the C-terminal 'core' of a precursor peptide is transformed into the mature natural product by a suite of peptide modifying enzymes that are recruited by an N-terminal 'leader' peptide. 12,13 Pyridine synthases are responsible for the late stage formation of the class-defining nitrogenous heterocycles at the core of the thiopeptide pharmacophores.14\u201316 The key reaction is thought to entail an intramolecular formal [4+2] cycloaddition between two dehydroalanines (Dhas) followed by elimination of water and leader peptide (LP) to yield a tri-substituted pyridine core (Fig. 1a).17,18 In contrast to other DAs, this reaction is non-spontaneous and incurs a significant thermodynamic penalty due to the inactivated nature of the reaction subcomponents. Synthetic versions of this cycloaddition are low yielding and require high temperatures.19
The in vivo manipulation of thiopeptide biosynthetic gene clusters has demonstrated that pyridine synthases are very promiscuous enzymes and can be used to generate a variety of thiopeptide derivatives with different sized macrocycles and pyridine substituents.20\u201325 More specifically, enzymatic macrocyclization is independent of any structural preorganization imposed by the core peptide, as neither its length nor rigidity prevent cyclization.23 Thus we reasoned that pyridine synthases might be able to catalyze an intermolecular reaction between isolated 2\u03c0 and 4\u03c0 components. Such a reaction would provide perhaps the most extreme example of substrate promiscuity and support a two-site model of substrate recognition. Therefore, we sought to test whether pyridine synthases TclM or TbtD, from the biosynthetic pathways of thiocillin (1) and thiomuracin (2), respectively, could catalyze an intermolecular reaction (Fig. 1b). Optimization of the enzyme reaction conditions was an important initial step to test this hypothesis because our previous work showed that the enzymes could be slow and several modifications known to be permitted in vivo either refused to be cyclized in vitro and/or generated by-products.26
We first looked to improve the in vitro activity of TclM and TbtD by investigating the influence of pH on the rate of pyridine formation. Several steps of the proposed mechanism could be influenced by pH: (1) tautomerization of the enamide to iminol, (2) elimination of water and (3) aromatization (Fig. 1a). We used our previously described solid-phase strategy to prepare substrates for TclM and TbtD (compounds 3 and 4, respectively, Fig. 2a, b) based on their respective precursor peptides, TclE and TbtA (Fig. 1c).26 Each substrate consisted of a simplified core with a minimal LP fragment that was previously found to be sufficient for complete processing.14,26 The TclM substrate (3), was synthesized with a 10-residue LP, while the TbtD substrate (4), had a 15-residue LP (Fig. 2a, b). Enzymatic reactions were monitored at neutral and basic pH by measuring the distinctive absorbance of the newly forming, tri-substituted pyridine at 350nm over time. Reaction rates were calculated based on standard curve (see SI). A significant increase in rate was observed for each enzyme at pH 9.0 (Fig. 2c). Specifically for TbtD, a nearly 10-fold increase in kcat was observed from pH 7.2 to 9.0 (Fig. 2d, S1). Although kcat at pH 9.0 is still generally considered low, it is comparable to other late stage RIPP-modifying enzymes.27\u201332
Next, we assessed whether pH influenced substrate binding. We measured the dissociation constant, Kd for TbtA bearing the 15-residue LP and MBP-TbtD via fluorescence polarization assay. A non-reactive substrate for TbtD, with alanines instead of Dhas, was synthesized and derivatized with fluorescein isothiocyanate (FITC) at the N-terminus (5). Kd's were determined at pH 7.2, 8.0 and 9.0 (Fig. 2d, S2). Effects of pH on Kd were minor compared to those on kcat. At pH 7.2, a Kd of 3.2\u03bcM was measured whereas values of 3.9 and 7.1\u03bcM were observed at pH 8.0 and 9.0 respectively. These data suggest that the pH does not significantly influence substrate binding.
Due to the pronounced binding affinity of TbtA's N-terminal 16-residue LP for TbtD,33 we sought to determine whether this region of the LP might further enhance the reaction rate by allosteric regulation in trans. Studies have shown that this region contribute much of the full-length leader LP binding affinity to TbtD (Kd = 1.3\u03bcM),33 but is not strictly essential for enzymatic processing.16,26 The 16-residue N-terminal fragment (6) was synthesized by SPPS and reaction rate for substrate 4 was measured at pH 7.2 and 9.0 in presence or absence of 6. No appreciable change in rate was observed (Fig. S3). These data suggest that the N-terminal LP fragment does not act as an allosteric modulator. In the context of full length TbtA, this fragment's higher affinity may allow the LP to bind first, thereby increasing local concentration of the core around the active site to facilitate faster modification.
As an initial test of TbtD's improved substrate promiscuity under the optimized reaction conditions we assessed its ability to cyclize TbtA LP mutants. Previously, alanine scanning mutagenesis had been used to investigate LP binding to TbtD16,33 but not substrate processing. We reasoned that similar experiments might identify residues within the LP that are important for catalysis in addition to acting as a metric for promiscuity. A suite of 16, largely alanine-substituted, LP variants were prepared in parallel by solid-phase peptide synthesis (SPPS, see SI). The LP variants were separately tested at pH 7.2 and 9.0, and LCMS analysis revealed several differences (Table 1, Fig. S4a\u2013q). Overall, 12 of the 16 substrates were processed at neutral pH, while 15 were cyclized under basic pH. Interestingly, only the H27A LP variant failed to cyclize under either condition. These data indicate that TbtD exhibits broader substrate promiscuity under basic pH.
With the enhanced activity of pyridine synthases confirmed, we sought to test whether TclM or TbtD could catalyze an intermolecular reaction. 2\u03c0 components for both TclM and TbtD were prepared by SPPS and consisted of the corresponding minimal leader sequences with a C-terminal Dha-thiazole. The TclM 4\u03c0 component was synthesized via SPPS following the same synthetic strategy that was used to prepare the intramolecular substrates. The TbtD 4\u03c0 component was synthesized in solution from thiazole building blocks following standard peptide coupling procedures (see SI). In either case, each 4\u03c0 component was designed to present the amide bond and Dha proposed to be involved in the cycloaddition plus two-to-three modified residues flanking either side. Incubation of each set of substrates with their respective pyridine synthases at pH 7.2 for 21 hrs yielded only trace amounts of product by LCMS. At pH 9.0, we again observed only trace amounts of product in reactions with TclM (Table S1). However, TbtD cleanly consumes both components and produces a new UV peak with characteristic absorbance at 350 nm and [m/z] consistent with a fully formed pyridine product (Fig. 3, S5a). The intermolecular reaction was scaled up and the identity of the product was confirmed by 1H and 13C NMR. TbtD is capable of recognizing the 2\u03c0 and 4\u03c0 reaction partners separately, without need for tethering between them, suggesting that an exceptionally broad array of macrocycles could likely be prepared by this enzyme.
In order to further define the limits of the TbtD-catalyzed intermolecular reaction, we prepared a small library of 2\u03c0 and 4\u03c0 substrates. With respect to the 2\u03c0 component, previous LP truncation experiments and the above LP variants have defined the important residues in the LP so we focused further variation on the C-terminal side on the Dha. The thiazole (Thz) was changed to an oxazole (Oxz, Fig. 4b, entry 2) or removed entirely (Fig. 4b, entry 3). These 4\u03c0 substrates were again synthesized via solution-phase chemistry and Dhas were installed either through alkylation-elimination chemistry of cysteine thiols or via mesylation-elimination of serine alcohols (see SI). As with the 2\u03c0 substrates, thiazoles were iteratively changed to oxazoles and residues flanking the necessary Dha were removed to isolate the crucial components of the 4\u03c0 substrate. For each new reaction, a percent conversion was calculated based on LCMS analysis and the rate of cyclization was measured by change in absorbance at 350 nm over time relative to a standard curve of purified product (Fig. 4b, S5a\u2013h, S6). The results illustrate several key requirements for intermolecular substrates (summarized in Fig. 4a): (1) the C-terminal heterocycle must be present in the 2\u03c0 component (Fig. 4b, entry 3), but a thiazole can be exchanged for an oxazole without significantly perturbing the rate or conversion (Fig. 4b, entry 2); (2) TbtD is sensitive to changes to both the N- and C-termini of the 4\u03c0 component (comparing entry 1 to 6, 7 and 8 in Fig. 4b); (3) the bisazole motif is critical for cyclization; truncation to a single thiazole results in no product (Fig. 4b, entry 8); (4) removal of the C-terminal Dha results in no product \u2013 this Dha can be replaced with an alanine, albeit at significant cost to overall rate (Fig. 4b, entries 6 and 7); (5) in all 4\u03c0 substrates, exchanging thiazoles for oxazoles is tolerated but there is a decrease in efficiency in each case (comparing entry 1 to 2, 4 and 5 in Fig. 4b). Ultimately, all permissible reactions could be forced to full conversion with higher enzyme loadings, allowing isolation and structural confirmation of products by 1H and 13C NMR. These data demonstrate TbtD is tolerant of major changes to nearly every residue outside of the two Dhas undergoing pyridine ring formation.
In conclusion, we found that the thiomuracin pyridine synthase TbtD is capable of catalyzing an intermolecular pyridine formation in addition to its cognate intramolecular reaction. The intermolecular reaction proved possible only under rate-enhancing alkaline conditions, which allow an approximate 10-fold increase in enzyme turnover (kcat) while minimally affecting substrate binding (Kd). The thiocillin pyridine synthase, TclM, observed similar base-catalyzed rate-enhancement but could not perform an intermolecular reaction, suggesting that different families of pyridine synthases may have distinct substrate requirements. The intermolecular chemistry of TbtD provides evidence that pyridine synthases use a two-site model to engage and process their precursor peptides; this reaction is a strong indicator of this enzyme family's broad promiscuity, suggesting that their use as biocatalysts could be extended beyond natural thiopeptide scaffolds, to allow larger ring sizes, incorporation of non-natural functionality or even novel linear substrates. The intermolecular reaction may be of use in elucidating the mechanism of these enzymes and may provide a barometer for evaluating new pyridine synthases for biotechnology applications.
", "answer": "Thiopeptide pyridine synthases catalyze a multistep reaction involving a unique and non-spontaneous intramolecular aza-[4+2] cycloaddition between two dehydroalanines to forge a tri-substituted pyridine core. We discovered that the in vitro activity of pyridine synthases from the thiocillin and thiomuracin pathways are significantly enhanced by general base catalysis and that this broadly expands the enzymes substrate tolerance. Remarkably, TbtD is competent to perform an intermolecular cyclization in addition to its cognate intramolecular reaction, underscoring its versatility as a biocatalyst. These data provide evidence that pyridine synthases use a two-site substrate recognition model to engage and process their substrates.", "id": 629} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nclinical practice gives students the opportunity to make decisions , apply theories , prioritize those decisions , learn time management , and provides them with a chance to practice their clinical skills ( 2 , 3 ) . in a supportive learning environment ,\nclinical teachers encourage students to be independent in their learning and they advise them to be self - reliant ( 4 , 5 ) .\nhowever , some earlier studies conducted in iran have shown that clinical learning is usually ineffective for nursing students ( 6 ) , students experience high levels of anxiety ( 6 ) , nursing instructors are mostly inexperienced , and clinical learning fails to integrate theory and practice ( 7 )\n. however , few studies are available on the reasons behind the ineffectiveness of clinical learning in nursing education .\nthis study aimed to find out the factors that can impede nursing students clinical learning .\nparticipants were purposively selected among the nursing students who were studying in their seventh semester of the baccalaureate program in 2014 and who had clinical rotations in the hospitals affiliated to bushehr university of medical sciences .\nafter the researchers explained the objectives of the study to the participants , 12 students , out of 30 , volunteered to participate and to keep reflective journals . in a briefing session , the first researcher gave them a notebook and presented them with a verbal description of how to complete the journaling task .\nthe students were asked to write in their journals about their own experiences , important learning events , attitudes , feelings , and their own opinions on their clinical learning experiences in after passing a week of their practical course in each ward .\nthey were asked to return these anonymous journals to the researcher at the end of each week .\n46327 ) and review board of bushehr university of medical sciences approved and granted the proposal of this study .\nall of the participants signed a written informed consent form and were assured that their written texts would not be shown to any persons other than the researchers and would not affect their clinical evaluation scores .\nthus , the researchers received each journal from the participants , and then they considered them carefully .\nanalyses consisted of identifying , coding , and summarizing themes according the approach suggested by graneheim and lundman ( 8) . in order to evaluate the data s trustworthiness , the researchers gave summarized results to a few participants to confirm the credibility of the data analysis .\nthe established relationship between the researchers and participating students facilitated a trust - based relationship between the parties in relation to data generation and treatment .\ncredibility was also enhanced because of the prolonged engagement of the researchers with participants and having experience in the practical field as an instructor .\nparticipants were purposively selected among the nursing students who were studying in their seventh semester of the baccalaureate program in 2014 and who had clinical rotations in the hospitals affiliated to bushehr university of medical sciences .\nafter the researchers explained the objectives of the study to the participants , 12 students , out of 30 , volunteered to participate and to keep reflective journals . in a briefing session , the first researcher gave them a notebook and presented them with a verbal description of how to complete the journaling task .\nthe students were asked to write in their journals about their own experiences , important learning events , attitudes , feelings , and their own opinions on their clinical learning experiences in after passing a week of their practical course in each ward .\nthey were asked to return these anonymous journals to the researcher at the end of each week .\n46327 ) and review board of bushehr university of medical sciences approved and granted the proposal of this study .\nall of the participants signed a written informed consent form and were assured that their written texts would not be shown to any persons other than the researchers and would not affect their clinical evaluation scores .\nthus , the researchers received each journal from the participants , and then they considered them carefully .\nanalyses consisted of identifying , coding , and summarizing themes according the approach suggested by graneheim and lundman ( 8) . in order to evaluate the data s trustworthiness , the researchers gave summarized results to a few participants to confirm the credibility of the data analysis .\nthe established relationship between the researchers and participating students facilitated a trust - based relationship between the parties in relation to data generation and treatment .\ncredibility was also enhanced because of the prolonged engagement of the researchers with participants and having experience in the practical field as an instructor .\nthe participants believed that interpersonal communication between students , nurses , teachers , physicians , and patients was one of the most important factors affecting clinical learning . from the students point of view\n, a positive and friendly relationship between students , nurses , and instructors affects the clinical learning environment and increases their self - confidence and learning .\nstudents described that communication with their classmates in the educational environment was positive and satisfying .\nmy friend and i always are together , and ask each other questions that we have , and this is good .\n however , relationships were not respectful from the side of the qualified nurses , and this affected the students motivation to learn .\nsome nurses frowned at me , when i asked them a question . from the participants point of view , some nurses did not trusted the students ' work , and they blamed them when anything bad happened in the ward .\nparticipants emphasized that the competence of the clinical instructors and staff nurses -as a role models- was a crucial factor affecting their learning in the clinical field .\nto the students , their instructors kindness , knowledge , clinical skills , expertise , and self - efficacy were among the main characteristics that made them good role models .\nsome instructors have sufficient knowledge and skills , so they have a higher self confidence level , and they help us ( students ) to understand how to do our duties . some of them say to follow whatever staff do . in this\n however , the majority of the students believed that the lack of clinical experience among instructors was the main barrier that decreased their competency to train students effectively .\nnonetheless , although they were technically skillful , they did not always have a caring attitude and sometimes performed procedures without upholding any standards .\nparticipants revealed that there is a theory - practice gap in the clinical setting , and this hindered their clinical learning .\nthe participants indicated that they confronted problems such as confusion about how to do procedures based on theoretical knowledge or like nurses in real situations .\none student wrote : we did nt see many things that we have learnt in theoretical class .\nif we follow standards , the nurses may laugh us and i dread this . \nparticipants wrote in their journals that the nurses were often unaware of educational objectives and the students learning needs ; further , their expectations of the students were not the same as the teachers. one of them wrote : the staff nurses demand that we do their routine tasks , such as checking vital signs and changing linens .\nthese are not useful for us , because these are repeated each day and we learnt them well , but we did nt learn some special procedures , like cpr .\nthe participants believed that interpersonal communication between students , nurses , teachers , physicians , and patients was one of the most important factors affecting clinical learning . from the students point of view\n, a positive and friendly relationship between students , nurses , and instructors affects the clinical learning environment and increases their self - confidence and learning .\nstudents described that communication with their classmates in the educational environment was positive and satisfying .\nmy friend and i always are together , and ask each other questions that we have , and this is good .\n however , relationships were not respectful from the side of the qualified nurses , and this affected the students motivation to learn .\nsome nurses frowned at me , when i asked them a question . from the participants point of view , some nurses did not trusted the students ' work , and they blamed them when anything bad happened in the ward .\nparticipants emphasized that the competence of the clinical instructors and staff nurses -as a role models- was a crucial factor affecting their learning in the clinical field . to the students , their instructors kindness , knowledge , clinical skills , expertise , and self - efficacy were among the main characteristics that made them good role models .\nsome instructors have sufficient knowledge and skills , so they have a higher self confidence level , and they help us ( students ) to understand how to do our duties . some of them say to follow whatever staff do . in this\n however , the majority of the students believed that the lack of clinical experience among instructors was the main barrier that decreased their competency to train students effectively .\nalthough they were technically skillful , they did not always have a caring attitude and sometimes performed procedures without upholding any standards .\nparticipants revealed that there is a theory - practice gap in the clinical setting , and this hindered their clinical learning .\nthe participants indicated that they confronted problems such as confusion about how to do procedures based on theoretical knowledge or like nurses in real situations .\none student wrote : we did nt see many things that we have learnt in theoretical class .\nif we follow standards , the nurses may laugh us and i dread this . \nparticipants wrote in their journals that the nurses were often unaware of educational objectives and the students learning needs ; further , their expectations of the students were not the same as the teachers. one of them wrote : the staff nurses demand that we do their routine tasks , such as checking vital signs and changing linens .\nthese are not useful for us , because these are repeated each day and we learnt them well , but we did nt learn some special procedures , like cpr .\nthe current study has shown that , despite the crucial role of appropriate relationships in students clinical learning experiences , it is not enough .\nthis finding was in line with findings of jahanpour et al . , who studied clinical decisionmaking in senior nursing students ( 2 ) .\naccording the participants in this study , the competence of their clinical instructors and the theory - practice gap were among the most important factors affecting them and their learning in clinical settings .\nsome earlier studies have also pointed out the role of clinical instructors and staff nurses as role models for nursing students learning in clinical setting ( 6 , 9 , 10 ) . in iran , many experienced nursing instructors who hold master s or phd degrees are reluctant to participate in clinical education , and so this role is mostly assigned to inexperienced , newly graduated nurses with master s degrees , or those who are still master s degree students .\nthese people are not ready to fulfill their role as competent role models . on the other hand , as cheraghi et al .\n( 7 ) reported , due to the domination of task - oriented work in clinical settings , nurses clinical behaviors can not support nursing students efforts to integrate theory and practice .\nthis study was only conducted in one nursing school , and this might limit the generalizability of the results .\nhowever , based on out findings , we can say that nursing students lack sufficient clinical learning due to unsupportive and inappropriate communication running throughout clinical settings , they lack effective role models , and they are harmed by the theory - practice gap . restructuring the healthcare setting so that experienced nursing instructors are encouraged to enter and participate in clinical settings , establishing appropriate workshops for preparing inexperienced nursing instructors for their roles as clinical instructors , and implementing appropriate strategies to motivate staff nurses to take part in the education of nursing students might help in decreasing the barriers to effective learning in clinical settings .", "answer": "backgroundclinical training is an integral part of nursing education ; however , some studies have shown that it is not always efficient.objectivesthis study aimed to find out the factors that can impede nursing students clinical learning.materials and methodsin this qualitative study , data were collected via reflective journal writing . \n purposeful sampling was used , and 12 senior nursing students were recruited to the study . \n the data were analyzed using a content analysis method.resultsthree main categories were derived , including inappropriate communication , ineffective role models , and theory - practice gaps . \n students perceived that inappropriate communication between instructors , staff members , and students had the greatest impact on student learning . \n the competence of clinical instructors and staff is an important factor affecting students training \n . the clinical learning environment does not always integrate theory and practice together.conclusionsnursing students did not experience effective clinical learning . \n having expert instructors and supportive communication are important factors in creating a clinical learning environment .", "id": 630} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen i hear the word quantitation , what comes to mind is the contrast between two famous 19th - century german scientists , alexander von humboldt and carl gauss , as described in measuring the world : a novel ( kehlmann , 2009 ) .\nvon humboldt was a great prussian explorer who made many discoveries , including electric eels , in his expeditions to south and central america , which included the casiquiare canal , which connects the orinoco and amazon rivers .\na man of extraordinary energy , he was the consummate quantitater he measured the heights of mountains and the numbers of lice on the heads of natives .\ngauss , as surveyor and astronomer for the kingdom of hannover , was also a quantifier , but with a different style .\ncharged with devising a practical method to survey on a spherical earth , he laid the foundation for a school of geometry that culminated in the work of riemann and the notion of curved space - time in einstein 's general theory of relativity .\nthe lesson here is that when you have a theory , measurement becomes very important and intellectually challenging .\nhave all the relevant parameters been measured ? have all the confounding complications been considered ?\ndoes the theory really fit to the data ? how accurately have the underlying quantities ( parameters ) been measured ?\nwhat is a model ? what is the difference ? in biology , we usually distinguish three types of model : conceptual models , mathematical models , and simulations ( bowne - anderson et al . , 2013 ) .\nthey all serve the same general purpose : to explain more complex phenomena in terms of more elementary processes or molecular interactions .\nthis can be in the form of a cartoon or picture that conveys the author 's idea or explanation of his or her results .\nbut can it really explain the data ? usually , more work is needed to establish the plausibility of a conceptual model .\na mathematical model is the development of the conceptual model into a system of equations .\nthe postulates are identified ( often in the form of parameters ) , and the implications or predictions are derived by solving the equations . the equations usually describe the average behavior of a large number of interacting molecules or entities a so - call mean - field theory ( although variances and other statistical properties can often also be calculated ) .\nthe solutions are then compared with the experimental measurements the quantitation of the data . if the equations can be solved analytically , all is well and good because this usually indicates that the solution is simple , or at least familiar . if not , numerical solutions are readily provided by such programs as matlab ( www.mathworks.com ) .\nthe predictions of the model ( with appropriate parameters ) can then be used to quantitatively account for the experimental data .\nthis is the process of curve fitting , which can be used to ask whether the theory actually fits the data ( i.e. , establish plausibility ) and to measure the underlying parameters and their uncertainties . a simulation is a computer - based imitation of a system . like a mathematical model , a simulation postulates interactions between underlying molecules or entities . unlike\na mathematical model , however , a simulation models individual behavior ( rather than mean behavior ) and often needs to be repeated a large number of times to obtain an accurate measure of the average behavior .\nsimulations are especially valuable when modeling small - number systems , which can display highly stochastic behavior .\nsimulations can be used for establishing the plausibility of a conceptual model , and by changing the parameters , the simulator can experiment with the model to gain insight into how it works .\nthe first is that they often contain many details such as the precise initial conditions or the order of the interactions . in this sense\nthey are often like experimental results , which also depend on many details ( e.g. , the composition of the buffers ) . in light of well - documented cases in which the results of simulations depended on these details , it has been argued that a simulation should be treated like an experimental result in the sense that it should be confirmed in different laboratories before being accepted ( mitchell , 2009 ) .\na second potential limitation of simulation is that although it can establish plausibility of a mechanism , it might provide only limited insight .\nthis is especially the case if the system behavior is unexpected and the elementary interactions give rise to so - called emergent or collective behavior . in this case\n, the behavior of the simulation may be as mysterious as the biological phenomenon being modeled , even when the simulator can probe the model by varying the model parameters ( analogous to performing wet experiments ) .\nan alternative approach is to use so - called toy models ( or idea models ; mitchell , 2009 ) , which , while oversimplifying the system under study , are nevertheless simple enough to solve using a mathematical model , thereby providing insight into mechanism .\nan example of a toy model is turing 's reaction - diffusion mechanism of pattern formation ( turing , 1952 ; gierer et al . , 1972 ) .\ni do not want the reader to think that simulations are always inferior to mathematical models . indeed , there are now very good algorithms that have solved many of the technical problems associated with simulations ( e.g. , the gillespie algorithm ; doob , 1945 ; gillespie , 2007 ) .\nthe physicist freeman dyson recounts attending a conference at which enrico fermi criticized the complexity of dyson 's model by quoting the mathematician john von neumann ( dyson , 2004 ) : with four parameters i can fit an elephant , and with five i can make him wiggle his trunk . \nactually , it is not so easy to model an elephant with four parameters , although we recently achieved it , even making the trunk wiggle with the fifth parameter ( mayer et al . , 2010a ) !\nif a model has a small number of premises or parameters that give rise to broad and/or unexpected implications , then we might call it a theory .\nevolution the modern evolutionary synthesis is a theory because it makes a relatively small number of postulates yet predicts a very broad range of observations , including the laws of inheritance and models of population genetics .\nit could be argued that other models , especially those underlying spatial oscillations ( e.g. , turing patterns ) and temporal oscillations ( e.g. , the cell cycle ; see later discussion ) , rise to the level of theories .\ntheories and models can be used to establish plausibility , sufficiency , or impossibility . they can also be used to measure .\nthe importance of establishing plausibility is illustrated by a recent example in which a textbook conceptual model was shown not to explain the observations .\nmyosin cortex was driven by a gradient of tension ( bray and white , 1988 ) . however , using experiments ( laser cutting ) and theory , it was found that cortical flow in the one - cell caenorhabditis elegans embryo is driven not by a gradient in tension but by a gradient of contractility ( i.e. , motor activity ) : in the direction of flow , there is no tension gradient , but , counterintuitively , in the transverse direction , there is a tension gradient but no flow ( mayer et al . , 2010b ) !\nthis example shows the importance of developing a mathematical model ( and testing it ) to establish the plausibility of a conceptual model .\ntwo examples of the use of theory to establish sufficiency are the action potential and the cell cycle . in a remarkable feat that serves as a foundation for neurobiology , hodgkin and huxley ( 1952 ) formulated and solved equations showing that the action potential in nerve cells can be accounted for by the voltage - dependent interactions between sodium and potassium conductances ( channels in the modern parlance ) .\nthe second example concerns the cell division cycle . following seminal discoveries showing the necessity of phosphorylation for controlling the transitions between phases of the cell cycle , tyson and novak ( 2011 ) showed the sufficiency of phosphorylation networks to drive the transitions . in other words\n, they answered the question , what do you need to build a molecular switch \n( answer : feedback and cooperativity ) , and , by doing so , they made the problem of the cell cycle finite . in the process , they made key predictions that were confirmed experimentally and they explained many phenotypes .\nan excellent example of the use of theory to show impossibility is the prescient work of ken machin ( machin , 1958 ) .\nhe proved that the periodic bending motion of cilia and flagella ( such as sperm tails ) can not be driven by motor activity localized to the base of the cilium only : if the beating were driven by a whip - like process at the base , the amplitude would die out with a characteristic shape due to the damping from the fluid .\nthis shape is not consistent with the observed beating patterns , whose amplitudes are maintained along the length of the flagellum .\ninstead , he proposed motors all along the length , with a traveling wave of activity propagating from base to tip .\nnot bad , considering that the motor dynein had not been discovered ( gibbons and rowe , 1965 ) , nor was it known whether the filaments inside the flagellum ( the microtubules ) slid or contracted ( they slide ; satir , 1965 ) . of interest\nshowing impossibility is the most powerful use of mathematical models : it allows hypotheses to be falsified , which is difficult to achieve using simulations . in my work , i have used theory as a tool to measure molecular properties and interactions . for example , we used precise mechanical measurements on hair cells the sensory receptors underlying the sensation of sound and acceleration to estimate the force needed to open a single channel , the displacement associated with the opening of the channel 's gate , and the number of channels ( howard et al . , 1988 ) .\nin other work , we used theory to infer the bending stiffness of actin filaments and microtubules from an analysis of their shape fluctuations ( gittes et al . , 1993 ) .\nmore recently , we showed how molecular interactions between kinesin motor proteins and microtubules can give rise to length - dependent microtubule depolymerization , which may play a key role in determining the size of organelles such as the mitotic spindle ( varga et al . , 2006 , 2009 ;\nthese include the following : \n morphology : what determines the size , number , and shape of cells and organelles?signaling : how do molecules compute , and what is the role of spatial localization and compartmentalization?scaling : how do we bridge from one scale to another ? are there universal laws ?\nmorphology : what determines the size , number , and shape of cells and organelles ?\nsignaling : how do molecules compute , and what is the role of spatial localization and compartmentalization ? scaling : how do we bridge from one scale to another ? are there universal laws ?\nespecially important is to understand how variability is minimized within a cell to produce reproducible structures and signals , and amplified among cells to enlarge the number of stimuli to which a population of cells can respond .\nthere has been rapid development of single - molecule techniques , making it possible to manipulate individual molecules using optical and magnetic techniques and to visualize their activity inside cells using fluorescence microscopy . in this way\nit is even possible to sequence single molecules of dna ( www.pacificbiosciences.com ) . at the whole - cell level\nthe developments are as impressive : image processing techniques can be used to segment single cells in tissues to measure shape and activity , their total protein assayed by mass spectrometry , and their genomes sequenced .\nthese studies have revealed remarkable cell - to - cell variability of identical cells .\nhand in hand with these developments , we must have theory and models to make sense of the experimental results , as exemplified by gauss , rather than the collection of data for their own sake .\ni predict that in the future , theory will drive biology as it does physics and engineering .", "answer": "quantitative biology is a hot area , as evidenced by the recent establishment of institutes , graduate programs , and conferences with that name . \n but what is quantitative biology ? what should it be ? and how can it contribute to solving the big questions in biology ? \n the past decade has seen very rapid development of quantitative experimental techniques , especially at the single - molecule and single - cell levels . in this essay \n , i argue that quantitative biology is much more than just the quantitation of these experimental results . instead , it should be the application of the scientific method by which measurement is directed toward testing theories . \n in this view , quantitative biology is the recognition that theory and models play critical roles in biology , as they do in physics and engineering . by tying together experiment and theory , \n quantitative biology promises a deeper understanding of underlying mechanisms , when the theory works , or to new discoveries , when it does not .", "id": 631} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n measuring performance of health systems is an essential tool for health policy - makers to conduct analysis and track change .\nthe 2000world health organization ( who ) report reflects that promoting health status , fairness in financing and responsiveness are the three main goals of evaluating health system performances ( 2 ) .\nresponsiveness refers to the ability of a health system to respond to the legitimate expectations of the population ; this is associated with the non - medical aspect of the health system and environment in which the people are treated ( 2,3 ) .\n\" respect for human right \" and \" client - orientation \" are two broad categories of responsiveness .\nfurthermore , respect for human right consists of dignity , autonomy , communication and confidentiality ( 2,4 ) .\nclient orientation includes prompt attention , quality of basic amenities and access to social support networks as well as choice of provider . in 2000 , iran s health system was ranked 100th in terms of responsiveness ( 2,5 ) .\nprompt attention and dignity were the most important domains of responsiveness of health systems for the iranian populations ( 6 ) .\nbesides , urgent and special attention was recommended to improve the responsiveness of the health system ( 7,8 ) . \n \n in a survey on health system responsiveness in tehran ,\nmore than 90% of the households believed that responsiveness was very important ( 5 ) .\nin addition , it was reported that responsiveness was better for outpatient care than inpatient care ( 9 ) .\nmost of the studies on health care responsiveness have focused on household survey , and only a few studies were conducted to address the responsiveness of a health system to inpatient care ( 5,6,10,11 ) .\nmoreover , there is a gap in the concerning patients views on health system responsiveness in iran . \n \n\nthe 11th government , elected in june 2013 , took health as the top priority of its administration and has been implementing a health sector evolution plan ( hsep ) since may 6 , 2014 ( 12 ) .\nhsep is a national plan , with two main phases : the first phase relating to improving fair access to healthcare and quality of inpatient and outpatient care in hospitals and the second to the public health care ( 13 ) .\nhsep aimed to provide the followings : health insurance coverage to all uninsured individuals , reducing out - of - pocket expenses for inpatient services , providing financial protection of patients with specific diseases and poor patients , encouraging medical doctors to stay in deprived areas through motivational policies , improving quality of care through increasing specialists , and improving hospital amenities and lodging services ( 13,8 ) .\nthis study aimed at examining the effect of hsep on health system responsiveness in kermanshah , western iran .\nthe findings may contribute to improvements in the responsiveness of the health system in this area of iran . \n\n\n this was a cross - sectional study conducted on the responsiveness of the hospitals in admitted patients in kermanshah in 2015 .\nthe city has seven public university hospitals with a total number of 1,570 active beds and two private hospitals .\ndata were collected from six public university hospitals with the exception of the seventh university hospital , which was a psychiatry hospital .\na sample of 335 patients was calculated using the formula for single population proportion at 50% proportion of responsiveness ( as no evidence was available from similar studies in the area ) , 5% level of significance and 0.05 margin of error .\nthe proportionate allocation to population size technique was employed to collect data from each hospital .\nat least three days hospitalization by a patient and age above three years were the inclusion criteria whilst patients who refused to participate or admission in intensive or critical care units were excluded . \n \n\ndata were collected using standard world health survey(whs ) questionnaire , which was developed by world health organization ( who).this questionnaire is a valid , reliable and comparative instrument that contains questions about the importance of responsiveness domains from an inpatient s point of view , health services utilization and people 's view about the responsiveness domain of inpatient services ( 14 ) .\nitems in each component of responsiveness were as follows : prompt attention ( 2 items ) ; communication ( 2 items ) ; human gentility and dignity ( 2 items ) ; patient s participation in decision - making and autonomy ( 2 items ) ; confidentiality and trust ( 2 items ) ; choice of provider ( 1 items ) ; quality of basic amenities ( 2 items ) ; and access to social support ( 2 items ) . in this study ,\nresponsiveness of the hospitals was considered as a dependent variable while the socio - demographic variables of the patients were the independent variables .\nwe used a five - point likert scale where 5was very important / very good , and 1 represented least important / very poor .\nthe responsiveness score for each domain was obtained by dividing the sum of the scores within the domain by the number of items in the likert scale .\nthe stata version 12 statistical package was used to analyze the responses of a five - point likert scale data .\nthe frequency distribution , ranges and mean ( sd ) were used to describe the data . the principal component analysis ( pca )\nsimilar to another study in iran ( 5 ) , we used 0.4 and above as a cutoff for factor loading in the pca .\nthe overall relationship between the socio - demographic variables and health system responsiveness was checked by chi - square test . \n\n\n this was a cross - sectional study conducted on the responsiveness of the hospitals in admitted patients in kermanshah in 2015 .\nthe city has seven public university hospitals with a total number of 1,570 active beds and two private hospitals .\ndata were collected from six public university hospitals with the exception of the seventh university hospital , which was a psychiatry hospital .\na sample of 335 patients was calculated using the formula for single population proportion at 50% proportion of responsiveness ( as no evidence was available from similar studies in the area ) , 5% level of significance and 0.05 margin of error .\nthe proportionate allocation to population size technique was employed to collect data from each hospital .\nat least three days hospitalization by a patient and age above three years were the inclusion criteria whilst patients who refused to participate or admission in intensive or critical care units were excluded . \n\n\n data were collected using standard world health survey(whs ) questionnaire , which was developed by world health organization ( who).this questionnaire is a valid , reliable and comparative instrument that contains questions about the importance of responsiveness domains from an inpatient s point of view , health services utilization and people 's view about the responsiveness domain of inpatient services ( 14 ) .\nitems in each component of responsiveness were as follows : prompt attention ( 2 items ) ; communication ( 2 items ) ; human gentility and dignity ( 2 items ) ; patient s participation in decision - making and autonomy ( 2 items ) ; confidentiality and trust ( 2 items ) ; choice of provider ( 1 items ) ; quality of basic amenities ( 2 items ) ; and access to social support ( 2 items ) . in this study ,\nresponsiveness of the hospitals was considered as a dependent variable while the socio - demographic variables of the patients were the independent variables .\nwe used a five - point likert scale where 5was very important / very good , and 1 represented least important / very poor .\nthe responsiveness score for each domain was obtained by dividing the sum of the scores within the domain by the number of items in the likert scale .\n\n the stata version 12 statistical package was used to analyze the responses of a five - point likert scale data .\nthe frequency distribution , ranges and mean ( sd ) were used to describe the data . the principal component analysis ( pca )\nsimilar to another study in iran ( 5 ) , we used 0.4 and above as a cutoff for factor loading in the pca .\nthe overall relationship between the socio - demographic variables and health system responsiveness was checked by chi - square test . \n\n\n three hundred thirty five , 190 ( 56.7% ) male and 145 ( 43.3% ) female , patients with the mean ( sd ) age of 41.5 ( 2.36 ) yrs . and the age range of 3 - 92 yrs.were included in the study . of the respondents ,\n92.8% had health insurance coverage , and 44.7 % were illiterate ( table 1 ) . \n \n the respondents rank on the level of importance of the health system responsiveness based on the domains of the responsiveness questionnaire is shown in fig .\nthe proportion of patients who rated the responsiveness of the hospitals as important or very important based on quality of the basic amenities , communication and dignity domains accounted for 94% , 91% and 90% , respectively .\nthe social support domain was considered as the least domain as only 77% of the patients rated this domain as important or very important . \n \nproportion of the participants who rated the responsiveness domain as important / very important \n the mean performance of each domain of the health system responsiveness is shown in table 2 .\nthe best and worst performance for domains of dignity and autonomy were 82.2 and 62.5 , respectively . \n \n\nthe findings indicated that 68% of the variance of the overall responsiveness score was explained by four components .\nthe first component which contained communication , dignity and autonomy explained 31.4% of the variance ; the second component contained confidently and social support and explained17.6 % of the variance ; the third component contained quality of basic amenities and choice domain and explained 11% of the variance and the fourth component contained dignity domain only and explained8% of the variance . \n \n\nthe empirical analysis revealed no significant association between total health system responsiveness scores and gender , education , age , health insurance coverage , and working status of the respondents . \n\n\n this study was the first of its type after health sector evolution plan ( hsep ) .\nthe aim of this study was to describe health system responsiveness in western part of iran .\nhowever , several studies have been conducted on health system responsiveness before hsep elsewhere ( 5,10,11,16 ) .\nresponsiveness of the health system is the result of interactions between health system agents and the patients ( 16 ) , which is related to the patient s well - being ( 17 ) .\nthe well - being of the patients is influenced by health system and the health system s responsiveness to the patients ( 18 ) . \n \n\nquality of basic amenities , dignity , communication and prompt attention received higher scores in terms of importance .\nthis implies that from patient s point of view , these domains are more important than other domains of responsiveness . in addition , compared to previous studies in iran , patients kept their preferences about responsiveness domains . \n \n in this study ,\nthe mean performance of each domain of the health system responsiveness was not much different except for autonomy that was rated the least . in another study that assessed the responsiveness of hospitals to inpatient care in zanjan reported an overall responsiveness score of 58.4 ( 10 ) .\nsimilarly , karami - tanha et al . found hospital responsiveness score of 57 to patients with heart failure ( 15 ) .\nfurthermore , a household survey on responsiveness of health systems to outpatient and inpatient services in tehran reported 70.6 responsiveness score ( 5 ) . generally , the overall score of responsiveness of the hospitals to inpatient services in our study was higher than the scores reported in previous studies in iran .\nbesides , hospital responsiveness scores in our study were higher than the scores reported in studies elsewhere ( 9,21,22 ) , but lower than the scores reported in germany ( 23 ) . \n \n in this study , dignity , confidentiality , and quality of basic amenities had the best performance .\nthis finding is in line with the reports of several studies ( 11,15,17,18 ) , and with that of rashidian et al . , but the quality of basic amenities in their report was the second worst performance ( 5 ) . in previous iranian studies , social support / confidentiality/ dignity ( 11 ) , dignity/ confidentiality/ prompt attention/ ( 5 ) , dignity/ confidentiality/ prompt attention ( 15 ) confidentiality/ communication / prompt attention ( 10 ) were reported as the best performing domains . unlike our study , a study in china reported social support to be the best performance domain ( 24 ) .\nconfidentiality and dignity domains achieved highest scores in the health system of iran before and after hsep .\nin addition , a high score in the quality of basic amenities means that the rooms in the hospitals were clean and there were enough waiting and examination rooms .\nin fact , after hsep , public hospital rooms were renovated and lodging and welfare equipment were purchased ( 12 ) . in this study , the autonomy domain had the worst performance score followed by choice domain .\nthis finding is similar to the findings reported in several other studies ( 5,10,15,22,23 ) . in the above - mentioned study of iran , autonomy/ quality of basic amenities ( 5 ) , autonomy/ communication ( 11 ) , choice/ autonomy ( 10 ) , and autonomy / choice received the least score ( 15 ) . in this study ,\nperformance of hospitals with respect to communication , prompt attention , social support , choice and autonomy were rated 4th to 8 , respectively .\ntherefore , providing training for the health care providers and improving their knowledge is necessary to achieve a higher score in the autonomy and choice domains . \n \n in this study\n, the principal component analysis revealed that responsiveness for inpatients care included communication dignity/ autonomy , confidently/ social support , and lastly quality of basic amenities / choice as the main factors . in a study conducted in taiwan , five factors of respect , access , confidentiality , basic amenities and social support were extracted .\nthese five factors revealed acceptable internal consistency , four of which were significantly correlated with the overall responsiveness score ( 25).in other studies , communication , autonomy and confidentiality were the main factors ( 5,21 ) . while the majority of the above - mentioned reports included both inpatient and outpatient cares , this study was limited to inpatient care and university hospitals . \n\n\n this study indicated a high rate of overall responsiveness score of each of the domains compared to other similar previous studies in iran .\nalthough it is difficult to reach a conclusion , our findings may show better responsiveness of the health system than the previous reports . the relatively higher responsiveness of the hospitals in the \" quality of basic amenities \" domain may be a direct result of huge resources use that was allocated to the hospitals during hsep .\nfinally , improvement in client - oriented domains of health system responsiveness such as quality of basic amenities and prompt attention may require large investments and additional resources , while improvement in", "answer": "background : responsiveness is one of the three main goals of the health system introduced by world health \n organization . \n this study aimed at examining health system responsiveness after health sector evolution plan in \n kermanshah , western iran . \n\n \n methods : a sample of 335 hospitalized patients was selected using proportionate allocation to population size \n method in the city of kermanshah ( iran ) in 2015 . \n world health survey ( whs ) questionnaire was used to collect \n data . \n data were analyzed using descriptive statistics and principal component analysis by stata 12 . \n\n \n results : the overall health system responsiveness score was 72.6 . \n the best and worst performance for domains \n of dignity and autonomy were 82.2 and 62.5 , respectively . \n socio - demographic variables of the patients \n had no significant effect on the total health system responsiveness score . \n the principal component analysis findings \n indicated that 68% of the variance of the overall responsiveness score was explained by four components . \n\n \n conclusion : the overall responsiveness score of each of the domains was higher than that of other similar \n previous studies in iran . although it is difficult to reach a conclusion , our findings may show better responsiveness \n of the health system compared to the previous reports", "id": 632} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe management of parkinson 's disease ( pd ) is often enhanced by complementary rehabilitation strategies , such as exercise .\nfor example , studies of resistance [ 13 ] and endurance [ 47 ] exercise training have improved balance , gait , postural stability , and physical function and reduced falling in people with pd .\ntai chi , a traditional chinese martial art that involves meditation and slow , graceful movements , is often recommended to reduce stress , improve mood , flexibility , physical function , and balance [ 810 ] .\nstudies of tai chi in people with chronic disease including parkinson 's disease and old people have supported the potential for benefit , with gains in the quality of life , postural stability , gait , physical function , immune function , cardiometabolic disease risk factors , and other health - related parameters [ 4 , 1119 ] . however , research on the effectiveness of tai chi is contradictory due to inconsistencies in the implementation of the tai chi movements , limited samples , and the lack of randomized control trials .\nthe purpose of this study is to investigate the effects of a randomized control trial of therapeutic tai chi training on improving the motor function and physical function of parkinson 's disease patients .\nall participants gave informed consent in accordance with the procedures of the parkinson 's disease center and the sports medicine center of the asan medical center . \nthe participants of this study were 24 clinically stable patients with diagnosed idiopathic parkinson 's disease recruited from the parkinson 's disease center in asan medical center in seoul , republic korea .\neligible participants met the following inclusion criteria : ( 1 ) hoehn - yahr stage 1 or 2 and ( 2 ) stable drug regimen .\nvolunteers were excluded from the study if they had ( 1 ) severe cognitive impairment , ( 2 ) concomitant severe neurologic , cardiopulmonary , or orthopedic disorders , ( 3 ) specific contraindications to exercise , or ( 4 ) they had recently participated in any physiotherapy or rehabilitation program . \nthe volunteers were screened for inclusion and exclusion criteria based upon the medical history and physical examination .\nparticipants were randomized to either a twelve - week intervention of therapeutic tai chi ( ttc ) or a non - exercise control group ( see figure 1 ) .\nthe ttc group visited the clinic 2 times a week and performed home - based activity 1 time per week for 12 weeks .\neach ttc session started with a 10-minute stretching exercise warm - up , followed by 30 minutes of tai chi exercises , and ending with 10 minutes of meditation and 10 minutes of stretching exercise cool - down .\nthe exercise was performed within the intensity ranges of 11 to 15 ( light to somewhat hard ) on the borg ratings of perceived exertion ( rpe ) scale .\nstudy outcome measures were obtained at baseline ( prerandomization ; one week prior to the start of the program ) and within one week following the end of the 12-week intervention .\nthe outcome measures included several test of physical function ( lateral stance , agility , tandem gait , timed up and go , and six - minute walk ) and the unified parkinson 's disease rating scale ( updrs ) sections 13 .\nall the tests were performed in the same order , at the same time of day , and when the participant felt best .\nthe participant stands with hands on hips with eyes closed ; when ready , the participant stands on the foot of choice for as long as possible , with the knee of the other leg flexed to 90 degrees .\nwhen a light comes on , they jump up as fast as possible in response to a single light stimulus .\nthe tandem gait test was used to assess balance , appendicular coordination , and gait , which involves multiple sensory and motor systems .\nthe participant walks in a straight line while touching the heel of one foot to the toe of the other with each step . for the timed up and go test , the participant was seated in an arm chair ( 45 cm high ) with their back against the chair . on a signal\n, they stand up , walk 3 meters as quickly and safely as possible , turn around , walk back to the chair , and sit down with their back against the chair .\nthe six - minute walk test was applied as a test of cardiorespiratory endurance for daily physical activities .\nthis test measures the distance that can be walked at a self - paced velocity on a flat hard surface over a period of six minutes . \nan analysis of variance ( anova ) for repeated measures with one between factor ( treatment group ; ttc versus control ) and one within factor ( time ; pre- and postintervention ) was used to evaluate the effects of the intervention .\na total of 11 participants were randomized to the ttc and 11 participants to the control condition .\ntwo subjects in the control group did not complete the study for personal reasons unrelated to the study . \nas shown in table 3 , significant changes were observed in the mentation , behavior , and mood subscale and the motor subscale of the updrs , with no significant main effects on the activities of daily living scale ( adl ) , balance , or reaction time .\nhowever , there were significant interactions between time and intervention group on the updrs activities of daily living subscale ( figure 2 ) .\nhowever , as shown in figures 3 and 4 , there were significant ( p < 0.05 ) interaction effects for balance ( one - leg standing test ) and reaction time ( light stimulus ) .\nin this study , we investigated the motor and nonmotor effects of therapeutic tai chi exercise training on participants with pd .\nthe findings of our study showed modest effectiveness of tai chi training on people with parkinson 's disease , with significant interaction effects for balance , reaction time , and adls .\nthese findings support that tai chi is effective in improving some aspects of motor function , most notably reaction time and balance .\nin addition , pd participants reported an improvement in their ability to engage in their activities of daily living .\nexercise therapy has a major role in the rehabilitation of the patients with parkinson 's disease [ 26 , 27 ] .\nregular physical activity may increase the functional ability and enhance the capacity for independent living by decreasing the need for assistance with the activities of daily life .\nin addition , exercise may achieve the goal of neuroprotection , slow disease progression , and postpone disabilities [ 28 , 29 ] .\nseveral cohort studies have described the functional achievements of moderately affected parkinson 's disease participants who have undergone intensive standardized exercise training [ 3033 ] .\nhowever , burini et al . reported in a study with a crossover design that a 7-week tai - chi and aerobic exercise training did not affect the severity of neurological signs and symptoms as assessed by the updrs or have any significant impact of training on the attendant disability .\n. showed that physical therapy is mainly focused on mobility rather than various neurologic symptoms such as rigidity and tremor .\nreported that some aspects of the mobility and balance functions were positively affected by tai chi exercise .\nhowever , assessing the mobility and balance function by only one item , such as the walking function , is not very representative of the spectrum of the motor signs and symptoms .\nfurthermore , there is little attention toward non - motor symptoms such as fatigue mood and health quality of life , all of which may be altered by exercise [ 27 , 3740 ] . in a recently published clinical trial ,\nli et al . found beneficial effects of tai chi exercise on balance , physical function , and falls , suggesting that tai chi is an appropriate physical activity for patients with parkinson 's disease and it might be useful as a therapeutic exercise . the ability to balance is related to the control of the center of gravity within the base of support .\nkoller and huber found that the balance impairment in older adults with a longer duration of pd does not usually respond to levodopa ; 38% of the persons with pd experience fall , 13% fall more than once per week , and some studies have reported that pd patients fall repeatedly throughout the day .\npersons with pd are 5 times more likely to suffer falls - related injuries such as hip fractures than healthy older adults . \nreaction time for agility was measured in the present study and improved with ttc training .\nttc training has benefits for postural stability in elderly people , including patients with pd , likely by acting on a number of sensorimotor systems that contribute to postural control [ 12 , 43 , 44 ] .\nthis improvement combined with the observed improved agility performance confirms the separate observations of previous studies showing that ttc training results in better balance capacity , proprioception function , and muscle strength [ 11 , 4547 ] .\nwhile our study and other studies have shown enhanced balance and agility resulting from tai chi , further work is needed to confirm that these improvements in fall risk factors actually result in fewer falls , as there are somewhat contradictory findings in the literature [ 19 , 45 , 48 ] .\nphysical function refers to the assessment of the capability to complete a specific task rather than assessing the physiologic - derived attributes , and it is believed to reflect the ability to carry out activities of daily living . in the present study , we assessed the physical function with the timed up and go , tandem gait , and six - minute walk tests .\nthe timed up and go test showed no significant change after training , which is in contrast to the findings of li et al . .\nthese differences may be due to differences in the programs of tai chi , the wider range of disease severity in the study by li et al . , or the smaller numbers of participants in our study .\nthe timed up and go test largely depends on the muscular power and strength of the quadriceps and the hip extensor muscles to arise from a chair [ 49 , 50 ] .\nit may be that our version of tai chi does not substantially improve lower extremity power .\nthe results of the tandem gait test and the six - minute walk test were also not changed after 12 weeks of ttc training .\npoor performance on the tandem gait and six - minute walk could result from several potential factors , including poor cardiorespiratory fitness and gait or balance abnormalities [ 23 , 51 ] .\nmany of the pd participants likely had poor cardiorespiratory fitness and inadequate levels of physical activity , as shown by garber and friedman .\nconsistent with this finding , all of the participants in this study had below normal results on the six - minute walk test , suggesting that poor cardiorespiratory fitness , gait , and/or balance may have been an important determinant of performance .\nother studies of tai chi have not shown an improvement in cardiorespiratory fitness , and our results are consistent with these previous findings .\nthis study investigated motor function and the severity of motor and non - motor symptoms and signs .\nthese motor and nonmotor symptoms and signs were not improved after treatment , although self - reported engagement in activities of daily living was enhanced by tai chi exercise .\nttc training involves splitting up complex movements into simple motor tasks and incorporating simultaneous movements , which is also beneficial for parkinson disease patients .\nthus , this study lends additional evidence for tai chi as a complementary treatment for people with parkinson 's disease one that will allow them to engage more fully in their activities of daily living .\nfurther studies are needed that will consider the effects of various components of a tai chi program and also to help to identify the intensity , duration , and frequency of tai chi exercise to attain optimal benefits .\nfurther , the influence of various medication and dietary factors may moderate the effects of exercise , and this has also not been studied .", "answer": "objective . \n the purpose of the study was to investigate the effects of a 12-week program of therapeutic tai chi on the motor function and physical function of idiopathic parkinson 's disease patients ( pds ) . \n methods . the participants were 22 clinically stable pds in hoehn - yahr stages 1 - 2 randomly assigned to a therapeutic tai chi group ( ttc , n = 11 ) or a control group ( con , n = 9 ) . \n two subjects in control group did not complete the study for personal reasons . \n ttc was performed three days a week ( 60 min / session ) . \n motor symptoms by the updrs were assessed , and tests of physical function were administered before and after the 12-week trial . results . \n the ttc group , as compared to the con group , showed changes in the mentation , behavior , mood , and motor scales of the updrs ( p < 0.05 , p < 0.01 , resp . ) , with no significant main effects on the activities of daily living scale ( adl ) . \n however , there was a significant interaction between the time and intervention group on adl ( p < 0.05 ) . \n there were no significant main effects for any of the physical function variables . \n there were significant interaction effects in balance and agility ( p < 0.05 , resp . ) . conclusions . \n this study showed that ttc training had modest positive effects on the functional status of parkinson 's disease patients .", "id": 633} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nretinoblastoma ( rb ) is the most common intraocular malignant tumor in childhood , with an incidence of 1 in 15000 live births .\nit may affect one eye ( unilateral rb ) or both ( bilateral rb ) during the first five years of life .\nalthough extensive epidemiologic studies have been done to study this tumor , the results have been more often misinterpreted at the expense of mutation theory which has prevailed until recently in spite of the outstanding evidence against it . in the present review\nthe authors analyze the most relevant epidemiological issues concerning retinoblastoma , in the light of recent developments highlighting the role of aneuploidy and genetic instability in the pathogenesis of this eye cancer .\nthe most important studies to investigate the pathogenesis of retinoblastoma began with a paper published by knudson in 1971 , when the author , after investigating the age distribution and laterality of a cohort of 48 rb patients , concluded that the disease could be inherited and formulated the so - called two - hit theory in order to explain its pathogenesis . in reality , no clues about the inheritance of retinoblastoma could be deducted from such a small sample .\nin fact , in his first report on this matter , knudson referred to earlier , smaller series showing that , in retinoblastoma survivors with bilateral disease , the proportion of affected offspring closely approximated 50% , as in dominant ( mendelian ) inheritance . from an original , mathematical analysis of the above data , knudson inferred that retinoblastoma is caused by two sequential ( two hit ) mutational events . according to this hypothesis , in the dominantly inherited form of the disease ,\none mutation is inherited via the germinal cells and the second spontaneously occurs in somatic cells of the retina and other tissues of the body . on the contrary , in the nonhereditary form\nthe different timing and cell type involved by the two mutations determines the different clinical phenotype , with all bilateral and a minority of the unilateral cases being classified as hereditary , and the remaining unilateral cases being included in the sporadic group ( table 1 ) . during the following forty years of epidemiological , clinical , genetic , and biological research in this field , with the discovery of the rb1 as the prototype tumor suppressor gene , the medical establishment agreed on the pathogenetic two - hit theory which was further expanded by knudson , in many other scientific articles and review papers [ 624 ] .\nthis generated the widespread conviction that rb is caused by two mutational events leading to the loss or inactivation of both alleles of the rb1 gene , as still believed by some authors .\nas mentioned above , the original input into the possible genetic derivation of retinoblastoma was based on limited evidence showing an apparently dominant mendelian distribution of the disease in the offspring of bilaterally affected individuals , thus allowing knudson to conclude that bilateral rb is inherited through the germ cells .\nminimum or no disagreement had been appeared on this account in the literature during the last four decades . in an attempt to elucidate this issue ,\nwe have performed an analysis of the distribution of the disease in the offspring of unilaterally affected rb survivors , referred to the department of ophthalmology \nwe discovered that in a total of 16 children born to 12 unilaterally affected patients , 8 ( 50% ) were healthy and 8 ( 50% ) affected with rb ( table 2 ) . using the reasoning of knudson\n, it would be easily concluded that the unilateral disease phenotype is inherited and not sporadic , and this would be in sharp contrast with the current knowledge according to which bilateral rb is always hereditary and unilateral rb is almost always sporadic .\nit was reported by knudson and confirmed by others that about 10% of all rb cases do have a positive family history . in other words , the family history of the index case offers at least one other affected member , either a parent or another close relative . in this case , it is assumed that the events leading to the inactivation of the rb1 gene run in the family , and therefore the first \nhit is transmitted through the germline , exactly what happens in bilateral rb , but with one difference ; bilateral rbs , which after knudson are all to be considered hereditary , are also assumed to have inherited the first hit through a mutation in one of the parent 's germ cells , but they are the only affected members in their families .\nwe should therefore be reasoning that , since familial rbs share the same pathogenetic mechanism with bilateral ( hereditary ) rb , the vast majority of these cases should show the bilateral phenotype . to be more accurate ,\nwe could make a calculation of the percentage of familial rbs carrying the unilateral phenotype . as a matter of fact\n, table 1 shows that the unilateral phenotype accounts for about 1/3 of all hereditary cases ( or about 30% ) , and since familial rb represents the 10% of all rbs , it comes out that rbs carrying the unilateral phenotype , within the familial group , should not be more than 3% ( i.e. , the 30% of the 10% ) . as a matter of fact , a meta - analysis of a cohort of 3584 patients ( table 3 ) , reported by us elsewhere [ 4 , 5 ] , reveals that on a total of 344 ( 9.5% ) familial cases , 83 ( 24% ) show the unilateral phenotype , instead of the predicted 3% , a rather unexplainable figure , in the light of the predictions made by the\nin 1986 , potluri and coworkers observed that the association of rb with the constitutional chromosome 13q deletion syndrome and the finding of 13q deletions or monosomy 13 in rb cells in individuals with normal constitutional karyotypes seemed to suggest that chromosome 13q could contain a gene responsible for tumor development in retinoblastoma .\nalthough the authors themselves acknowledged that other chromosome abnormalities , in addition to those involving chromosome 13 , are evident in retinoblastoma ( additional copies of 1q material in 44% of cases , isochromosome 6p , in 45% of cases , monosomy 16 , in 18% of cases , marker 1p+ , in 13% of cases , and homogeneously staining regions and double minutes , in 9% of cases ) , further investigations on this matter stressed the role of 13q deletions in the genesis of rb , thus reinforcing the belief that the loss or inactivation of the rb1 was the only responsible for rb to develop .\nbut it is well known that retinoblastoma is only one among many different tumors associated with deletions of chromosome 13 .\ncancers linked with these deletions include chronic lympocytic leukaemia ( cll ) , chronic myeloproliferative disorders , multiple myeloma , hepatocellular carcinoma ( hcc ) , nasopharyngeal carcinoma , benign and low - grade malignant lipomatous tumors , bladder cancer , malignant mesothelioma , and prostate cancer .\nthe same pleiomorphism in the phenotypic expression of cancers associated with rb1 gene mutations is therefore evident in 13q deletion syndrome .\nbut the most important consideration to be made about the association of 13q deletion syndrome and rb concerns the evident discrepancy existing between the expected and the real number of bilateral tumors among the patients affected by this genetic disorder . as a matter of fact\n, the 13q deletion syndrome must be confirmed by the cytogenetic analysis of peripheral blood lymphocytes , and it is due to a \ndeletion of the long arm of chromosome 13 which involves , by definition , the rb1 gene locus . since the constitutional deletion of the rb1 gene can only be present if transmitted through the germ cells of one parent , it follows that all patients affected by 13q deletion syndrome and retinoblastoma belong to the hereditary group of knudson 's and must , therefore , express the bilateral disease phenotype .\nit happens , however , that this assumption does not fit the clinical reality . in table 4 a series of 13 cases of 13q deletion syndrome and retinoblastoma referred to us over the last four decades is reported .\nof these patients , only 4 had the bilateral disease phenotype , while the remaining 9 were unilaterally affected ( table 4 ) .\nthe mean age at diagnosis in this group , which is about 10 months , further reinforces the assumption that they must belong to the hereditary group of knudson 's , but the unilateral disease phenotype is unexplainably high . in the light of the two hit theory ,\nthe data summarized above do not have any rationalization , and the only plausible conclusion is that the assumptions made in regard to the role of the rb1 gene in retinoblastoma are incorrect .\nclinical epidemiology is a leading discipline in the understanding of disease pathogenesis and etiology , but , as any other scientific endeavor , it relies on the correct interpretation of the available data .\nthe proper analysis of data , in turn , relies not only on the individual researcher 's skill but also on social , economic , and political environment in which the data are analyzed .\nthe presumed genetic origin of rb and its relationship with the rb1 gene represent a clear example of how an entire body of prominent researchers may fail to question a flawed pathogenetic hypothesis ( i.e. , the two - hit theory ) , for the sake of personal , academic , or other interests .\nit was not by chance that we had to approach many different scientific journals to have access to the medical community about the role of aneuploidy and genomic instability in the genesis of rb [ 4 , 5 , 39 ] .\nwe are still optimistic , however , because our alternative pathogenetic explanation has finally appeared in recent ophthalmologic literature .", "answer": "retinoblastoma ( rb ) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so - called tumor suppressor gene , the rb1 gene . \n the pathogenetic mechanism behind this tumor was first hypothesized by knudson in 1971 and further confirmed by others who identified the rb1 gene whose loss or inactivation was claimed to be responsible for the disease . \n however , after about four decades of continuous research in the field of molecular biology , the evidence behind the role of the rb1 gene in rb appears to be seriously flawed in the light of epidemiological , biological , and clinical evidences . \n this editorial summarizes the inconsistencies on this subject . \n nevertheless , the molecular biology establishment still adheres to the biased view of the genetic origin of rb and other cancers , and hardly any alternative explanations are taken into account .", "id": 634} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndesktop computer and laptop use is becoming common , and computing - related musculoskeletal \n symptoms are considered important health problems in university students and office \n workers1,2,3,4 .\nprevious studies have indicated that improper sitting posture \n during visual display terminal ( vdt ) work ( e.g. , desktop computer or laptop use ) can induce \n musculoskeletal disorders , especially low - back pain3 , \n 4 ) .\ncarter and banister3 \n suggested that increased tension in ligaments and discs during a slumped sitting posture may \n lead to low - back pain .\ncross - legged sitting , a commonly adopted posture during daily living and vdt work , has been \n reported to induce a slumped sitting posture5 , 6 .\nlee et al.5 showed that the cross - legged sitting \n position leads to a greater slumped posture compared with an upright sitting posture during \n vdt work . to prevent the unwanted slumped posture , it is crucial to identify factors that \n contribute to slumped posture during cross - legged sitting .\nlimited hip flexion range of \n motion ( rom ) could be one possible risk factor for excessive lumbar flexion . because the \n lumbar spine and hip joint are connected via the pelvis\n, limited hip flexion can cause \n greater lumbar flexion through pelvic posterior tilt during the trunk flexion - related \n posture7 .\nalthough it seems reasonable that limited hip flexion rom leads to greater lumbar flexion \n during the cross - legged sitting posture , no study has investigated how hip flexion rom \n influences the kinematics of the lumbar spine in the cross - legged posture during vdt work . \n\nfurthermore , previous studies have not determined whether greater lumbar flexion during vdt \n work with a cross - legged sitting posture changes trunk muscle activities as measured by \n electromyography ( emg ) .\nonly one emg study revealed decreased emg activity in the internal \n oblique ( io ) muscles during the static cross - legged sitting posture compared with the static \n normal sitting posture8 .\nthus , the aim of \n the present study was to compare the lumbar flexion angle and trunk muscle activity in \n individuals with and without limited hip flexion rom during vdt work with a cross - legged \n sitting position .\nall subjects showed \n right - leg dominance and performed computer work more than 20 hours per week .\nmeasurements of \n the right hip flexion rom were used to classify subjects into the experimental or control \n groups . according to previous findings9\n, \n sufficient hip flexion rom was defined as more than 120 of hip flexion , and limited hip \n flexion rom was defined as 110 in this study .\nsubjects with more than 120 of right hip \n flexion rom ( one female , six males ) were classified into the control group , and subjects \n with no more than 110 of right hip flexion rom ( eight males ) were classified into the \n experimental group .\nsubjects were excluded if they had acute low - back pain , orthopedic \n damage , or lower extremity injury during the last 6 months .\nin addition , individuals with \n hip flexion rom between 110 and 120 were also excluded in this study .\nthe inje university \n faculty of health science human ethics committee approved this study , and each subject \n signed an informed consent form before participation . to measure hip flexion rom ,\nsubjects were placed in the supine position on a table , and an \n examiner passively flexed the right hip of subjects until further hip flexion was limited by \n firm end feel9 .\nthe fulcrum of a \n goniometer was placed on the greater trochanter , and the proximal and distal arms were \n aligned with the lateral midlines of the pelvis and femur , respectively .\nthe lumbar flexion angle was measured using eight vicon mx - t10 motion capture systems \n ( vicon motion systems ltd . ,\nthree reflective \n markers were placed on the bilateral anterior superior iliac spines and on the midpoint \n between the bilateral posterior superior iliac spines for the pelvic segment .\nadditionally , \n four reflective markers were attached to the first and second lumbar spinous processes and \n 3 cm bilaterally from the second lumbar spinous process for the lumbar segment .\nthe lumbar \n flexion angle was calculated by assessing the anterior rotation of the lumbar segment with \n respect to the pelvic segment using the cardan angle10 .\nthe trunk muscle activity of the bilateral rectus abdominis ( ra ) , \n external oblique ( eo ) , and io muscles was recorded using a synchronized surface emg system \n ( delsys inc . ,\nprior to attachment of the electrodes , skin preparation was \n performed by shaving the hair and cleansing with an alcohol swab .\neach electrode was \n attached along the direction of the muscle fiber based on placements suggested by \n criswell11 .\nemg signals were acquired \n at a sampling rate of 1,000 hz with a bandwidth of 20450 hz and converted into \n root - mean - square ( rms ) data . to normalize emg data of the trunk muscles , reference voluntary \n contraction ( rvc ) data of trunk muscles\nwere collected when subjects were seated on a chair \n in a comfortable sitting posture with 90 of hip and knee flexion for 40 s. the rvc maneuver \n was repeated three times , and the mean value of the average muscle activity for the middle \n 30 s of the three trials was used to normalize trunk muscle activity . prior to vdt work , a laptop ( xnote r400 , lg , seoul , korea ) was placed on a 73-cm - high desk , \n and subjects sat on a height - adjustable chair without a backrest with 90 of hip and knee \n flexion .\nthe examiner confirmed the 90 hip and knee flexion position using a goniometer . \n for vdt work with a cross - legged sitting posture ,\nsubjects were instructed to cross the \n right leg over the left by putting the right knee on the left knee5 , 8 . following \n cross - legged sitting ,\nsubjected performed typing work in which they copied some text \n provided on the monitor by the korean version of hansoft .\nthe subjects typed for 1 min for \n each trial , and three test trials were conducted with 30-s rest periods between trials .\nthe \n average values of the lumbar flexion angle and emg activity of the trunk muscles for the \n middle 40 s of each trial were collected , and the mean values of three test trials were used \n for data analysis .\nthe subjects characteristics ( age , height , weight , hip flexion rom ) , lumbar flexion angle \n and trunk muscle activity during vdt work with cross - legged sitting in the experimental and \n control groups were compared using independent t - tests .\n, chicago , il , usa ) was used , and the statistical significance level \n was set at p = 0.05 .\nthe general characteristics of the subjects in the control group ( mean age 25.1 \n 1.5 years ; mean weight 62.6 5.7 kg ; mean height 171.9 6.9 cm ) and the experimental group \n ( mean age 23.6 1.5 years ; mean weight 67.4 4.1 kg ; mean height 175.1 4.5 cm ) were not \n significantly different ( p > 0.05 ) , except for the hip flexion rom ( 123.6 2.4 \n versus 102.5 3.8 ; p < 0.001 ) .\nthe lumbar flexion angle was significantly greater in the experimental group compared with \n the control group during vdt work with cross - legged sitting ( p = 0.017 ) ( table 1table 1 .\ncomparison of the lumbar flexion angle and trunk muscle activity between the two \n groups during visual display terminal work with cross - legged sittingvariablemean sdcontrol groupexperimental grouplumbar flexion ( )15.2 7.023.3 4.3*right ra activity ( % rvc)101.2 5.9100.5 8.2right eo activity ( % rvc)98.7 6.2113.3 30.4right io activity ( % rvc)91.4 7.9109.4 22.3left ra activity ( % rvc)101.3 7.1101.7 8.2left eo activity ( % rvc)98.3 5.0115.3 35.0left io activity ( % rvc)99.8 10.897.2 11.3rvc , reference voluntary contraction ; ra , rectus abdominis ; eo , external oblique ; io , \n internal oblique . *\nhowever , there were no significant differences in emg measures of trunk \n muscle activity between the control and experimental groups ( p > 0.05 ) .\nrvc , reference voluntary contraction ; ra , rectus abdominis ; eo , external oblique ; io , \n internal oblique . *\nin the present study , the subjects with limited hip flexion rom showed greater lumbar \n flexion compared with subjects with sufficient hip flexion rom during vdt work with \n cross - legged sitting ; however , these differences in hip flexion rom did not influence emg \n activity in trunk muscles .\nthe lumbo - pelvic - hip complex is connected via a kinematic link termed the lumbo - pelvic \n rhythm7 , 12 . during forward bending ,\nthe lumbar spine is flexed anteriorly with \n respect to the pelvis , while the pelvis is flexed anteriorly on the femur12 .\nwhen lumbar flexion is limited , greater \n hip flexion is required with pelvic anterior tilt throughout the lumbo - pelvic rhythm7 . in other words ,\ngreater lumbar flexion is \n caused throughout the pelvic posterior tilt when hip flexion is limited .\nthe results of our \n study imply that greater lumbar flexion compensated for insufficient hip flexion in subjects \n in the experimental group during vdt work with cross - legged sitting . despite significant differences in lumbar flexion between the experimental and control \n groups , emg activity in the trunk muscles was not significantly different between the two \n groups .\nsnijders et al.8 \n reported that the cross - legged sitting position decreased emg activity in io muscles due to \n increased stability in the sacroiliac joint .\nthe cross - legged sitting posture is performed \n by the combined motion of hip flexion and adduction .\nincreased tension in the biceps \n femoris , gluteus maximus and piriformis by hip flexion and abduction influences sacroiliac \n joint compression and tension in the sacrotuberous ligament , which can contribute to \n increased stability in the sacroiliac joint13,14,15 . \n\nalthough the hip flexion angle may have been influenced by differences in hip flexion rom in \n subjects in this study , sufficient hip adduction may have been possible for all subjects \n during vdt work with cross - legged sitting .\nwe suggest that the sacroiliac joint compression \n by hip adduction during cross - legged sitting may not differ between subjects with and \n without limited hip flexion rom , resulting in the absence of significant differences in emg \n activity in trunk muscles between the two groups .\nfirst , our study included a small sample size ; \n therefore , it is difficult to generalize our results .\nhowever , a previous study by lee et al.5 showed that trunk kinematics were immediately changed after assuming \n a cross - legged sitting posture during vdt work , and the trunk flexion angle then did not \n significantly change for 30 min .\nbased on previous findings , we consider that the kinematic \n data of the lumbar spine and emg data of the trunk muscles during vdt work with cross - legged \n sitting for short periods may provide meaningful information for individuals who prefer \n cross - legged sitting .", "answer": "[ purpose ] the purpose of this study was to compare the lumbar flexion angle and \n electromyography ( emg ) measurements of trunk muscle activity in individuals with and \n without limited hip flexion range of motion ( rom ) during visual display terminal ( vdt ) \n work with cross - legged sitting . \n [ subjects ] the 15 participants included a control group \n with sufficient hip flexion rom ( n = 7 ) and an experimental group with limited hip flexion \n rom ( n = 8) . [ methods ] all subjects performed vdt work with cross - legged sitting . \n the \n lumbar flexion angle was measured using a three - dimensional motion capture system , and the \n trunk muscle activity was recorded using a surface emg system during vdt work with \n cross - legged sitting . \n the differences in trunk flexion angle and trunk muscle activity \n between the two groups were analyzed using independent t - tests . \n [ results ] the lumbar \n flexion angle was significantly greater in the experimental group than the control group , \n although trunk muscle activity did not differ between the two groups . \n [ conclusion ] these \n findings suggest that limited hip flexion leads to greater lumbar flexion during \n cross - legged sitting .", "id": 635} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvero e6 cells were infected with 100 focus - forming units of ebov expressing enhanced green fluorescent protein . after a 1-h incubation , the inoculum was removed and replaced with media ( dulbecco s modified eagle 's medium with 2% fetal bovine serum , penn / strep , l - glutamine ) containing chloroquine ( sigma , st .\nthe supernatant was collected on days 1 , 3 , 5 , 7 , and 9 after infection and media replaced with fresh drug .\nviral rna was extracted from the supernatant and quantified by real - time quantitative reverse transcription pcr as previously described ( 10 ) .\nconcurrently , cell viability was assayed by using cell titer96 aqueous one solution ( promega , madison , wi , usa ) according to the manufacturer s instructions .\nec was determined by using prism6 ( graphpad software , san diego , ca , usa ) . when added 1 h after infection , chloroquine at 5 g / ml and 25 g / ml reduced the viral loads by 0.61 and 1.07 logs , respectively ( peak reduction observed on day 5 ) , without any significant cytotoxicity ( figure 1 ) .\nanalysis of the data from day 5 resulted in an ec50 of 1.77 g / ml and an ec90 of 23.34 g / ml , concentrations that are comparable with previous data ( 8) ; however , reductions in viral loads at these concentrations at other time points were negligible .\nalthough concentrations of > 50 g / ml of chloroquine reduced viral loads by 24 logs starting on day 3 , this decrease was accompanied by a high level of cytotoxicity ( > 50% ) that was evident both in the cytotoxicity assay and microscopically resulting in poor selectivity of chloroquine .\nviral loads from supernatants derived from vero cells infected with ebola virus expressing enhanced green fluorescent protein and treated with chloroquine at the indicated concentrations ( 0 , 5 , 25 , 50 , 100 , and 200 g / ml ) .\nsix - week - old balb / c mice or syrian hamsters ( both from harlan , indianapolis , in , usa ) were inoculated intraperitoneally with 100 50% lethal dose of ma ebov .\nthe mouse ( 11 ) and the hamster ( 12 ) are well - established disease models of ebov infection .\ntreatment groups ( mice and hamsters ) received 90 mg / kg of chloroquine alone ( intraperitoneally ) .\nan additional group of hamsters received 50 mg / kg of chloroquine ( intraperitoneally every 24 h ) in combination with 2.5 mg / kg doxycycline ( gavage every 12 h ) and 50 mg / kg azithromycin ( intraperitoneally every 24 h ) .\nafter inoculation , animals were monitored at least twice daily and euthanized by using a humane endpoint scoring criteria as approved by the animal care and use committee at rocky mountain laboratories ( hamilton , mt , usa ) .\ntwo of 3 mock - challenged mice did not survive because of chloroquine ( 90 mg / kg ) treatment alone ( figure 2 , panel a ) . only 2 of 9 mice infected with ma ebov and treated with\nchloroquine survived , and 1 of 9 mice infected with ma ebov and treated with vehicle survived . with median survival of 7 , 8 , and 8 d for mock - challenged / chloroquine - treated mice , ma ebov infected / chloroquine - treated mice , and ma ebov infected / vehicle - treated mice , respectively , treatment had no significant effect on survival .\nthis dose , although previously stated as the maximum tolerated dose in mice ( 8) , was not well tolerated by the animals in this study and clearly did not improve survival in animals challenged with ma ebov .\nsurvival of ma ebov - inoculated mice ( a ) and hamsters ( b ) treated with cq ( 90 mg / kg ) .\nc ) survival of ma ebov infected hamsters treated with a combination of cq ( 50 mg / kg ) , doxycycline ( 2.5 mg / kg ) , and azithromycin ( 50 mg / kg ) .\ncombo , combination of chloroquine , doxycycline , and azithromycin ; cq , chloroquine ; ebov , ebola virus ; ma , mouse - adapted .\nwhen the same dose ( 90 mg / kg ) of chloroquine was given to hamsters challenged with ma ebov , the study had to be terminated on day 2 after treatment .\nnearly all the treated animals , in both the ma ebov and the mock - challenged groups , died of acute toxicity after administration of chloroquine intraperitoneally , typically within 30 min after treatment ( figure 2 , panel b ) . in a separate study , hamsters were treated with chloroquine ( 50 mg / kg ) in combination with doxycycline ( 2.5 mg / kg ) and azithromycin ( 50 mg / kg ) to additionally provide broad - spectrum antimicrobial drug coverage .\nreperfusion injury of the gut after ebov disease , which would subsequently result in bacterial sepsis , has been suspected as a possible cause of death .\nthus , broad - spectrum antimicrobial drugs were proposed to help in this regard . in this study\n, no toxicity was observed in the mock - challenged group as a result of the combination treatment .\nhowever , treatment had no effect on survival ; no combination - treated or vehicle - treated groups survived , and median survival times were comparable ( figure 2 , panel c ) .\ndespite some activity of chloroquine against ebov in vitro , we observed no benefit to its administration in the mouse and hamster models . in the mouse model ,\na dose of 90 mg / kg resulted in toxicity but did not alter survival ; therefore , higher concentrations of chloroquine in the mouse would not be expected to be possible . in the hamsters ,\nthis dose was already lethal on its own . in the hamster model at a lower dose ( 50 mg / kg ) combined with doxycycline and azithromycin which together provide broad - spectrum antimicrobial coverage , in addition to doxycycline having a small antiviral effect against ebov \nprevious anecdotal reports of the incidental use of chloroquine in patients with filovirus infections also do not support any benefit from its use ( 13,14 ) .\ntogether , these data suggest that chloroquine is unlikely to provide any protection from ebov infection in humans .\ngiven its in vitro activity against many different viruses and its longstanding use in humans , chloroquine has been put into multiple clinical trials . during dengue virus infection ,\nviremia did not decrease ( 15 ) , and chloroquine neither prevented influenza virus infection ( 7 ) nor improved outcome of chikungunya virus infection ( 6 ) despite promising in vitro activity against these viruses .\nwhen taken together with previous findings for other less pathogenic viruses , the clinical use of chloroquine seems unlikely to provide any benefit for either prophylaxis or treatment of ebov .\nmoreover , chloroquine has a small therapeutic window ; dosing for treatment of acute malaria is 15 mg / kg , and lethality starts at 50 mg / kg .\nthus , current preclinical data do not support the continued consideration of chloroquine for use against ebov infections in humans .", "answer": "the antimalarial drug chloroquine has been suggested as a treatment for ebola virus infection . \n chloroquine inhibited virus replication in vitro , but only at cytotoxic concentrations . in mouse and hamster models \n , treatment did not improve survival . \n chloroquine is not a promising treatment for ebola . \n efforts should be directed toward other drug classes .", "id": 636} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\none of them is that development is the increase in production , promoting the health and therapeutic services level , and eliminating problems .\ntherefore , development as it is considered by people and national institutions is a complicated and multidimensional process that requires changes in social structure , accelerating economic growth , reducing inequality , eradicating poverty , establishing social justice and equality , and environment stability .\ntherefore , in order to achieve development , identifying developed and undeveloped regions is of great importance in the first step ( 1 ) . codifying and establishing development and success strategies in implicational and executive plans , studying and recognizing capabilities and shortcomings and deficiencies , determining development levels in regions based on a set of appropriate indexes are inevitable requirements through which executive managers will become enable to identify development strategies based on needs and specific conditions in each and propose plans consistent with the conditions in each region ( 2,3 ) . assessing and evaluating and determining priorities help executive managers meet necessary needs more quickly .\nhealth and therapy section is one of the sections in which prioritizing for meeting needs regarding resources limitation is essential ( 4 ) .\ninequality and its dimensions are indexes of underdevelopment because in fact countries are considered developed that have high economic and social indexes and the distribution of incomes and revenues and facilities is rather equal in them while in undeveloped countries the amounts of these indexes are low and there is inequality in their distributions ( 5 ) .\nnumerous indexes are considered for assessing development level with the limitations in a time interval or period and place range .\nthere has been a lot of efforts to define and design an appropriate instrument which is an indicator of the socioeconomic status of people in a society ( 7 , 8) .\nfor example , australian researchers believe that using an index such as the validity of residency place for determining the socioeconomic status of individuals is very questionable .\ntherefore , it is necessary to use different indexes for determining the socioeconomic status . among these different development indexes ,\nhealth care index is one of the most important indexes of progress and development in any country due to its significant role in providing the society s health and the success of national development programs depends highly on achieving these aims ( 9 ) .\na transient look at the health indexes in the country in the past decade shows the fast growing trend of the promotion of the indexes on one hand and inequalities in some indexes in different regions and provinces in the country on the other hand .\nit is necessary that in iran like in any developing country , special attention should be paid to the development of health and therapy section in order to improve the country s development status and position among other countries in the world since development in this section is the prerequisite for the development in other sections of the society . nowadays , the issue of development is a big concern in many countries . in other words , development is nothing more than making the living status and conditions more satisfying for people ( 10 ) . \n \n a lot of studies have been done about ranking the level of health indexes of development using statistical methods and mathematical patterns . in a research ,\nregions of portugal were assessed and ranked regarding development using factor and cluster analysis techniques in the time intervals of 1991 and 1995 ( 11 ) . in studies by soares et al . ( 11 ) in portugal and yanis and andriant ( 12 ) , regions are ranked using health and economy indexes by factor analysis and clustering and fuzzy logic models . despite all criticisms to using quantitative models in city issues since 1970 , mathematic models can give a clearer picture and understanding of city phenomena if they are established and codified in simple frameworks with limited number of variables .\nstandardized score and moriss s models are among quantitative models for assessing and ranking regions .\nstandardized score model is used for comparing indexes and obtaining a single index from the combinatory results of the indexes .\nin fact , the standardized score model can uncover main differences among regions regarding the determined indexes ( 13 ) .\nmorris model is also introduced as a model for ranking regions in terms of development by civil program of the united nations organization which is the most recent official model applied at an international level and is capable of being developed , replaced , and applied in the planning environments with various different scales . \n \n\ntherefore , for achieving this goal and establishing social equality , it is necessary to rank regions and identify their degree or level of development regarding health and therapy indexes , determining capabilities , shortcomings , and deficiencies .\nthe present study addresses the analysis of development levels in cities in tehran province regarding health infrastructural indexes using standardized score and morris inequality models . \n\n\n the present study is applied or pragmatic based on its aim and descriptive based on its nature . in this study ,\nthe cities in tehran were ranked based on health indexes in 2012 using standardized score and morris models .\nthe studied geographic scope was tehran province and the statistical population was 14 cities in tehran .\nafter studying the experts articles and opinions , 10 indexes were selected as health indexes including the ratio of active medical and therapeutic institutions to a population of one thousand individuals , the ratio of beds at active medical and therapeutic institutions to a population of one thousand individuals , the ratio of health therapeutic and medical centers to a population of one thousand people , the ratio of governmental public health and medical institutions to active health and medical institutions , the ratio of daily medical and therapeutic centers to active health medical and therapeutic centers , the ratio of 24-hour health medical and therapeutic centers to active health medical and therapeutic centers , the ratio of laboratories to a population of one thousand individuals , the ratio of pharmacies to a population of one thousand individuals , the ratio of radiology centers to a population of one thousand individuals , and the ratio of rehabilitation centers to a population of one thousand individuals .\nthe required data were gathered from the statistics center and tehran university of medical sciences using a researcher - made information list including items and questions about the name of the cities , the number of active medical and therapeutic institutions , available beds , the number of health and medical therapeutic centers , the number of governmental public health medical and therapeutic centers , the number of daily health medical and therapeutic centers , the number of 24-hour health medical and therapeutic centers , the number of laboratories , the number of pharmacies , the number of radiology centers , the number of rehabilitation centers , and the population of the cities . after the completion of the lists , the development in cities was ranked and calculated using morris inequality and standardized score models in excel in 2010 .\nthe calculations in the two methods are as follows : \n \n first , the indexes were standardized based on the city using standardized score model , as follows : \n \n which , ssij is standardized score of index i for city j , xij is amount of index i for the city j , x is mean of indexes and is standard deviation of the index i. \n \n then , the standardized score of each of the studied indexes in each city are added up together and the result is divided by the total number of indexes .\nthe obtained score is the average of the standardized score or the development index of any city that makes the comparison regarding development status possible as a single index : \n \n which , ssi is the index for city j and n is the number of considered indexes . \n \n in morris model , the development status or position of each region among other regions is determined based on the selected indexes using the gathered information for each region .\nthis method is used for reporting human resource development by the united nations and the obtained index is the evidence showing countries ranking regarding human resource development . in this method ,\nthe deviation of the numerical values of the index i in any region or area from the minimum of the index i among the regions or areas is divided by the range of the changes of that index , and the degree of the inconsistency or inequality of the numerical value of the index in relation to the dispersion index of its changes or variation range is computed ( r = x ( max ) - x ( min ) i ) . \n \n\n( 3)miiij = xijx(min)ix(max)ix(min)i \n \n which , miiij is the value of morris inequality index for i index in the region or neighborhood j , xij is the numerical value of the index i in the region or neighborhood j , x(min)i is the lowest value of the index i and x(max)iis the highest value of the index i. \n \n in the next step , the mean of the numerical values of morris inequality index for indexes in each region or neighborhood is applied as the criteria for determining the ranking or development status from the highest value ( the first ranking ) to the lowest ( the last ranking ) : \n \n which , miii is development index for region or neighborhood j , and n is the number of considered indexes . \n \n\nin addition , for determining the developmental gap in health and therapy section in cities , 5 classifications of developed , rather developed , intermediately developed , less developed , and undeveloped were considered .\nthen , for determining the distance between cities in 5 levels , first the range of changes in scores was obtained using a formula and then the distance between levels was calculated by b formula and as a result the cities were classified in 5 groups . \n\n\n based on the standardized score model , rey city has the best , and pishva city has the worst condition in terms of health indexes ( table 1 ) . \n \n\nbased on the standard score model , 28% of the cities were placed in developed group and 43% of the cities were in undeveloped group ( table 2 ) . \n \n\nbased on morris inequality model , rey has the best state and pishva has the worst state ( table 3 ) . \n \n based on morris inequality model , 28% of the cities were placed in developed group and 43% of the cities were placed in undeveloped group ( table 4 ) . \n\n\n the first step for developing health and therapy section and reducing the gap regarding health among different regions is to achieve a thorough understanding of the condition of the healthcare sector in the region .\nindexes of development in developing countries are not distributed equally in the regions and geographical zones .\none of the main indexes of development is health index or in other words , the degree to which a society benefits from the health and therapeutic services and facilities .\nthe developmental gap of these indices can be easily observed in the provinces and cities in the country . \n \n\nthe findings showed that regarding the rate of development in the health sector , there is a deep development gap among the cities in tehran and the distribution of health services and facilities in the cities of the province seems unbalanced and unequal.for determining the development of cities in the standardized model , five levels of highly developed , developed , developing , deprived , and very deprived were considered.based on standardized score and morris inequality , only 28% of the cities were placed in the developed countries and this is in line with the results obtained by tofighi et al ( 14 ) and mirvis ( 15 ) .\ntherefore , planners and policy makers should focus their efforts to find the cause of the gap in development.given the values of tables ( 1 ) and ( 3 ) , rey city has maintained its superiority over other cities and was considered as the developed city and pishva got the last ranking for the development of health indexes.the noticeable point is that tehran is in the third ranking despite the fact that it is the capital city which indicates that the geographical location can not be considered as the factor influencing the development of a city and this was confirmed in other studies ( 14).bahadori et al .\n( 16 ) also investigated the ranking of the health structural indexes in golestan province using scalogram method.the results showed that there is a large gap regarding the benefits of the health structural indexes among the cities in golestan province.aqqala city with 97 points enjoyed the most and azad city with 41 points enjoyed the lowest level of the benefits of health structural indexes respectively . in this study ,\nin the studies by nastaran ( 17 ) and zarabi in isfahan ( 18 ) , amini in all the provinces in the country ( 19 ) and taghvaee in all the provinces in the country ( 20 ) , similar results were obtained about the gap in enjoying the health structural indexes .\ntherefore , it is suggested that officials , authorities , and planners pay attention to eliminating the mentioned problems , achieving growth and equal regional development , balancing the pattern of the distribution of health services and facilities , and decentralization of them in some cities ( 21 ) .\nthe distribution of health services and facilities should be done based on the level or degree of underdevelopment in cities . in general , ranking the country s cities and provinces in health sector makes it possible for the related authorities to make more accurate planning , identify strengths and weaknesses , and prioritize resources adapted to the needs of each city and province . in summary\n, the results showed that statistical methods are effective tools for ranking and determining the status of development in the health sector .\nthe results of this study concerning the allocation of the health sector resources would be useful for health planners and policy makers . \n\n\n structural indexes have always been considered as one of the main factors influencing health status and life.thus , to achieve a fair , balanced , and equal state of health in the province , it is suggested to make plans and take actions based on facts and the development situation of provinces and cities in order to reduce the gap in accessing and enjoying health facilities and services among the cities.furthermore , it is suggested that in the first stages of city development , authorities need to focus on short term policies and equity in access and pay attention to the development of necessary services in developing and deprived cities over a medium and long term plan .", "answer": "background : one of the main indexes of development is health index or the degree to which a \n society enjoys health and therapeutic services . the present study was done with the aim to analyze \n development levels in cities in tehran regarding health infrastructural index using the standardized \n score and morris model . \n\n \n methods : this is a descriptive and pragmatic study which ranks 14 cities in tehran province using \n the standardized score and morris models based on 10 selected health indexes . the required data \n were gathered using a researcher - made information list and the information gathered from the statistics \n center and tehran university of medical sciences . \n the data were analyzed using excel software . \n\n \n results : the development coefficient in the studied cities varies from 0.595 to -0.379 so that rey \n city has the highest level of development and pishva city has the lowest level of development among \n the studied cities . the more number of the cities ( 43% ) was among the rather undeveloped group and \n none of the cities ( 0% ) was in the rather developed group . \n\n \n conclusion : regarding the findings , there is a big gap and difference regarding enjoying health and \n therapeutic infrastructural indexes among the cities in tehran province . \n therefore , it is suggested \n that development - oriented plans consistentent with development levels should be implemented in \n these cities .", "id": 637} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncatheter - based radiofrequency ablation ( rfa ) delivered during endoscopic retrograde cholangiopancreatography ( ercp ) has recently emerged as a possible therapeutic option within the bile duct 1 \n 2 \n 3 \n 4 .\nintrabiliary extension of neoplasm remains an important challenge in the endoscopic eradication of complex ampullary lesions 5 \n 6 , and rfa may represent a viable treatment adjunct for this problem .\nrecently , the use of rfa at the ampulla and within the distal bile duct has been described 7 \n 8 .\nherein we present 4 cases assessing the technical feasibility , safety , and treatment outcomes of rfa employed at the time of ercp to treat ampullary lesions with intraductal extension .\nthe study was conducted at the medical university of south carolina ( musc ) from july 1 , 2014 through october 1 , 2015 .\nafter institutional review board approval , we retrospectively identified eligible adult subjects through the musc endoscopy report database ( endoworks , olympus america , center valley , pa ) by searching for reports that contained the keywords radiofrequency ablation ( rfa ) and endoscopic retrograde cholangiopancreatography ( ercp ) .\nwe excluded patients who underwent rfa of a stricture not associated with an ampullary lesion .\nall procedures were performed by an experienced pancreaticobiliary endoscopist under general anesthesia using a side - viewing duodenoscope .\nampullary resection was performed either en bloc or in piecemeal fashion by delivering electrosurgical current through a snare with or without prior submucosal lift .\nintraductal extension of the lesion was assessed cholangiographically ( fig . 1 ) and/or visually ( fig . 2 ) . in some cases , a biliary sphincterotomy extension and papillary balloon dilation\nwas performed to expose the inside of the terminal bile duct for assessment and therapy .\nablative therapy was delivered using a standard argon plasma coagulation ( apc ) probe ( erbe usa inc . ,\nmariette , ga ) at a flow rate of 1.0 l / min to 1.2 l / min and 30 to 40 maximum watts ( w ) and/or the habib endohpb rfa bipolar cautery probe ( emcision united kingdom , london , united kingdom ) at 10 w for 60 to 90 seconds , extrapolating from manufacturer s recommendations of 7 to 10 w 120 seconds 9 .\ngiven the proximity to the pancreatic orifice and the benign nature of the target lesions , a shorter duration of treatment was chosen . in general , apc was reserved for treating exposed target tissue in the duodenum or very distal duct , whereas rfa was reserved for treating hidden or difficult to access tissue within the duct .\nall patients undergoing rfa received a temporary pancreatic stent ( 5 fr , 2 5 cm ) and rectal indomethacin to reduce the risk of post - ercp pancreatitis ( pep ) , as well as a plastic endobiliary prostheses to prevent biliary obstruction and cholangitis . \n\ncholangiogram showing a filling defect in the distal bile duct ( arrow ) representing bulky intraductal extension of an ampullary adenoma . \n\nendoscopic view of the papilla after ampullectomy demonstrating intraductal extension of the adenoma ( arrow ) . \ntechnical success was defined as the ability to successfully position the rfa probe across the biliary orifice and deliver thermal energy to the region of the papilla and terminal bile duct , resulting in coagulation of the visualized target areas .\nclinical success was defined as endoscopic absence of polypoid or adenomatous - appearing tissue at the treatment site and histologic absence of neoplasm based on extensive follow - up biopsies from the papilla , pancreaticobiliary septum , biliary orifice , and distal bile duct .\nwhen the distal bile duct was not fully exposed by prior sphincterotomy , a pediatric biopsy forceps was introduced into the distal duct to acquire tissue .\npatient demographics , procedure indications , and treatment outcomes are listed in table 1 .\nfour eligible patients were identified , all of whom were men with a mean age of 63 years ( range 54 84 ) .\nthree patients ( 75 % ) had a history of familial adenomatous polyposis ( fap ) .\nthree patients were treated for ampullary adenoma and 1 for ampullary adenoma with a focus of adenocarcinoma ( he declined surgical evaluation ) . \nfap , familial adenomatous polyposis ; lgd , low - grade dysplasia ; hgd , high - grade dysplasia ; imc , intramucosal cancer ; apc , argon plasma coagulation ; rfa , radiofrequency ablation ; pep , post - endoscopic retrograde cholangiopancreatography pancreatitis ; eus , endoscopic ultrasound \n video 1 presents a synopsis of 2 representative cases .\nall rfa procedures were technically successful , resulting in a perceptible tissue effect ( fig . 3 ) .\nrfa was performed immediately following endoscopic resection in 1 case and during a subsequent session in the remaining cases .\nthe mean number of rfa sessions per patient was 1.5 ( range 1 3 ) .\nall patients were discharged uneventfully after the procedure without any immediate adverse events ( aes ) .\none patient developed obstructive jaundice due to a fibro - inflammatory bile duct stricture at the level of prior rfa that manifested 3 days after biliary stent removal ( approximately 6 weeks after the rfa ) and has required ongoing endobiliary stent therapy in excess of 3 months .\n3 patients had visual and histologic evidence of complete eradication ; the patient with a focus of adenocarcinoma who declined surgery developed overt invasive ampullary cancer . \n\nvideo 1 this footage consists of 2 video clips demonstrating catheter - based rfa of intraductal ampullary adenoma\nalthough endoscopic ampullectomy is the preferred treatment for noninvasive ampullary lesions with a success rate reported as high as 92 % 10 , biliary extension of neoplasm represents a significant obstacle to endoscopic eradication .\nexposure and eversion of the adenoma through a biliary sphincterotomy to allow resection or ablation has been described in amenable cases 5 \n 11 \n 12 .\nhowever , broad adenomatous involvement of the distal bile is associated with limited treatment success ( < 50 % ) and has been considered an indication for surgical resection 5 .\nbased on its ease of use and the ability to precisely position the probe within the distal duct , radiofrequency ablation may represent the first viable treatment adjunct for this challenging scenario .\nto date , only single case reports of rfa for benign ampullary lesions have been described ; we aimed to expand our understanding of this technology by presenting our experience in 5 patients . \ncatheter - based rfa was technically successful in all cases , and based on short - term follow up in a small sample , may be safe and clinically effective .\nhowever , because rfa induces thermal injury and subsequent necrosis of the bile duct wall and beyond , several safety concerns exist .\nfirst , while rfa has been associated with a favorable safety profile when applied to malignant biliary strictures 1 \n 2 \n 3 \n 4 , it remains unclear whether rfa in the intra - pancreatic portion of the bile duct without the protective buffer of a surrounding tumor especially in the vicinity of the pancreatic orifice will be associated with an increased risk of pancreatitis . until additional data on the risk of post - ercp pancreatitis in this context\nif the pancreatic and biliary orifices are in close proximity , especially if adenoma appears to involve the pancreaticobiliary septum , it may be best to perform the rfa adjacent to a guidewire which has already been placed in the pancreatic duct ( subsequently guaranteeing pancreatic access for stent placement ) rather than adjacent to a plastic pancreatic stent which may be damaged or even fractured during rfa . \nanother safety concern is the development of clinically important post - rfa biliary strictures that occurred in 1 of our patients , akin to what has been observed in the esophagus after rfa of barrett s epithelium 13 .\nthis concern is particularly relevant in the context of benign ampullary disease in which patients do not typically undergo long - term stent placement , as is the case when rfa is performed for palliation of malignant strictures . along these lines , until additional data are available , we have attempted to minimize rfa across the cystic duct takeoff to avoid thermal injury - related obstruction of the cystic duct , which has intentionally been induced by electrohydraulic lithotripsy to treat refractory bile leak 14 . in our series\n, rfa appears to have provided effective adjunctive therapy in all 4 cases of benign pathology but was ineffective in the setting of early adenocarcinoma , underscoring the concept that surgical resection remains first - line therapy for ampullary cancer ( our patient declined surgery and chemoradiation ) . despite the apparent effectiveness for benign lesions , it is important to consider that intrabiliary extension is often nodular in nature , leading to heterogeneous contact between the rfa probe and the target tissue ; this may lead to incomplete therapy and/or an increased risk of buried neoplasm as is the concern when rfa is used to treat nodular barrett s esophagus .\nmoreover , it can be technically challenging to ensure circumferential contact of the probe and the target tissue within a dilated bile duct , even when luminal air is suctioned to induce collapse of the duct around the probe . in these cases , a balloon - based rfa device that flattens nodular tissue and maximizes treatment contact may be of value .\nan additional consideration is that the proximal extent of neoplasm is often difficult to assess cholangiographically and the role of cholangioscopy to guide probe placement should be further explored .\nprospective studies are necessary to evaluate these issues and determine the long - term effectiveness of this modality . in summary , catheter - based rfa after endoscopic resection of ampullary lesions that extend up the bile duct is technically feasible .\nconcerns regarding injury to the pancreas and bile duct as well as incomplete treatment of nodular target tissue exist and will be addressed by additional clinical experience and research .", "answer": "background and study aims : catheter - based radiofrequency ablation ( rfa ) delivered during endoscopic retrograde cholangiopancreatography ( ercp ) may represent a viable treatment option for intraductal extension of ampullary neoplasms , however , clinical experience with this modality is limited . \n after ampullary resection , 4 patients with intraductal extension underwent adjunctive rfa of the distal bile duct . \n all patients received a temporary pancreatic stent to reduce the risk of pancreatitis , as well as a plastic biliary stent to prevent biliary obstruction . \n three patients were treated for adenoma and 1 for adenoma with a focus of adenocarcinoma . during a short follow - up period , 3 patients experienced complete eradication of the target lesion , whereas the patient with a focus of adenocarcinoma had progression to overt invasive cancer . \n there were no immediate adverse events . \n one patient developed a post - rfa bile duct stricture , which has required additional endoscopic therapy . \n catheter - based rfa of ampullary lesions that extend up the bile duct is technically feasible . additional research is necessary to understand the risks and long - term benefits of this technique .", "id": 638} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nIsolation and X-ray characterization of palladium\u2013N complexes in the guanylation of aromatic amines. Mechanistic implications\n\nPaper sections:\nIntroduction\nN-Arylguanidines are important compounds with interesting biological activities [1,2] such as fungicides [3] and also in supramolecular chemistry as complementary partners of carboxylate and nitro groups [4][5][6][7]. Some of these guanidines are commercially used as antifouling agents in marine paints and in the formulation of protective surface coatings [8][9][10]. N-Arylguanidines can be obtained by aniline insertion into the corresponding carbodiimide [11][12][13][14][15][16][17][18]. This nucleophilic addition can be efficiently catalyzed by palladium salts [19], such as PdCl 2 or Pd(OAc) 2 in homogenous phase. Also recently we have reported that palladium nanoparticles supported on magnesia can be a solid catalyst for this process [20]. Working with PdCl 2 (NCCH 3 ) 2 in dichloromethane we were able to isolate two types of palladium complexes with iodoaniline and guanidine, respectively, (see Scheme 1) that give some clue about the reaction mechanism of the catalytic process.
\n\nResults and Discussion\nIn order to provide further support to the mechanistic proposal for the C-N insertion promoted by palladium(II) suggested by us [20], in the present report we describe the study of palladium-catalyzed guanylation of three additional anilines (1a-c) Scheme 1: Isolation of trans-dichlorobis(4-iodoanilino-\u0138N)palladium(II) and trans-dichlorobis [1,3-diisopropyl-2-(4-iodophenyl)guanidino-\u0138N(aryl)]palladium(II) complexes formed by reaction of PdCl 2 (MeCN) 2 with 4-iodoaniline (upper row) or with 4-iodoaniline and N,N'-diisopropylcarbodiimide (lower reaction).
Scheme 2: Isolation of trans-dichlorobis [1,3-diisopropyl-2-(aryl)guanidino-\u0138N(aryl)]palladium(II) complexes (4a-c) by reaction of PdCl 2 (MeCN) 2 with anilines 1a-c and N,N'-diisopropylcarbodiimide (2). Dashed lines indicate the formation of trans-dichlorobis(anilino-\u0138N)palladium(II) complexes (3a-c) as primary intermediates during the reaction, and their subsequent reaction with 2 to led 4a-c.
with N,N'-diisopropylcarbodiimide (2). For these reactions we have been able to characterize three palladium complexes of the type of bis(anilino)Pd(II) (3a-c) as well as three palladium complexes of the type of bis(guanidino)Pd(II) (4a-c) (Scheme 2) whose structures have been characterized by singlecrystal X-ray structural analysis, as well as to obtain evidence for the intermediacy of these complexes in the catalytic process. Overall the present data reinforce the previous proposal for the mechanism of aniline guanylation.
When a stoichiometric (2:2:1) mixture of anilines 1a-c and carbodiimide 2 with PdCl 2 (MeCN) 2 is stirred at 60 \u00b0C in CH 2 Cl 2 , evolution at initial reaction times of a solid precipitate is observed (Scheme 2). Filtration of these precipitates and subsequent washing with CH 2 Cl 2 renders three solids whose combustion analysis is in accordance with the percentages expected for dichlorobis(anilino-\u0138N)palladium(II) (3a-c) (see Supporting Information File 1, experimental section). IR spectra of complexes 3a-c show the characteristic absorption peaks due to the coordinated anilines 1a-c (see Supporting Information File 1, Figures S1-S3); these are compatible with the proposed structure for these intermediates. Complex 3a derived from 1a has been recently characterized by single-crystal X-ray diffraction [21] showing similar coordination to trans-dichlorobis(4- iodoaniline-\u0138N)palladium(II) complex recently published by us [20]. Compounds 3a-c were also characterized by solid state 13 C NMR spectroscopy that gave spectra showing carbon peaks compatible with the proposed structure (see Supporting Information File 1, Figures S4-S6).
After prolonging the reaction time, the initially evolved precipitate undergoes dissolution indicating that it has been transformed under the reaction conditions. At this stage, filtering of the transparent orange-red (4a,b) and red (4c) solutions followed by subsequent addition of ethyl ether or toluene and slow solvent evaporation at ambient temperature allows the formation of crystals with suitable quality for a crystallographic diffraction study. The structures of these intermediates solved by X-ray analysis showed that these compounds corresponding to trans-dichlorobis[arylguanidino-\u0138N(aryl)]palladium(II). Figure 1, Figure 2 and Figure 3 present ORTEP views of complexes 4a-c as well as selected views along some crystallographic axes (see Tables S1-S3 and also Figures S7, S11 and S15 in Supporting Information File 1, and for full details of the crystallographic data see Supporting Information File 2).
Besides X-ray crystal structure analysis, palladium complexes 4a-c were also characterized by NMR spectroscopy, ESIMS and combustion analysis (see experimental section in Supporting Information File 1). 1 H, 13 Similar reactions were carried out mixing anilines 1a-c and N,N'-diisopropylcarbodiimide (2), but in this case in the presence of only a catalytic amount of PdCl 2 (NCCH 3 ) 2 (4 mol %) (Scheme 3). Under these conditions no evidence for the formation of palladium complexes (3a-c) and (4a-c) could be obtained due to the low amount of palladium and no solid precipitates were observed. In contrast, in the presence of catalytic amounts of palladium, formation of the corresponding N-arylguanidines was observed in almost quantitative yield. These guanidines 5a-c formed by nucleophilic attack of anilines 1a-c to N,N'-diisopropylcarbodiimide (2) catalyzed by palladium were fully characterized by analytical and spectro- scopic data (see Supporting Information File 1, experimental section).
Structure of guanidine 5a was confirmed by single-crystal X-ray analysis, Figure 4 shows the corresponding ORTEP for compound 5a as well as some views of the crystal packing (see also Supporting Information File 1, Table S4 and Figure S20 and for full details of crystallographic data see Supporting Information File 2). Beside X-ray crystal analysis of guanidine 5a, guanidines 5a-c were also characterized by 1 H, 13 C and 19 F NMR spectroscopy and combustion analysis (see Figures Overall the information obtained from the experiments performed in the presence of a large palladium excess, in which two kinds of palladium complexes have been detected and isolated, with the formation of guanidines under conditions in which a catalytic amount of palladium is present, allows us to make reasonable mechanistic proposals. Thus, upon contacting anilines 1a-c and PdCl 2 (MeCN) 2 , a rapid formation of dichlorobis(anilino-\u0138N)palladium(II) (3a-c) complexes should take place. These palladium complexes will interact with the N,N'-diisopropylcarbodiimide (2) giving rise to the dichlorobis(guanidino-\u0138N)palladium(II) (4a-c) complexes. When Pd is used in catalytic amounts, cleavage of this bis(guanidino-\u0138N) complex by aniline will form another dichlorobis(anilino-\u0138N)palladium(II) (3a-c) completing one cycle and liberating guanidines 5a-c as free products of this catalytic reaction with high yields and selectivities (see Scheme 4). In this mechanism the rate determining step will be the attack of dichlorobis(anilino-\u0138N)palladium(II) (3a-c) to the N,N'-diisopropylcarbodiimide (2) (Scheme 4).
In this process, coordination of nitrogen to palladium should strongly reduce the nucleophilicity of the corresponding nitrogen atom and, therefore, the attack at the carbodiimide would be significantly slowed down compared to free uncoordinated aniline. However, this negative effect of palladium coor- dination to aniline should be overcompensated by coordination of carbodiimide to palladium in close proximity to aniline in fixed geometry as indicated in the presumed intermediates 6a-c. There are precedents in the literature [22] showing that palladium(II) can interact weakly with accumulated carbodiimide bonds, but this type of complex is typically very labile and difficult to isolate under the reaction conditions due the presence of an aniline excess, and for this reason we have been unable to isolate labile intermediates 6a-c. This preassociation between complexes 3a-c and carbodiimide 2 to form intermediates 6a-c would make easier the key step of C=N insertion leading to guanidines (Scheme 4).
Alternatively, it can be also envisioned that the acidity of hydrogen atoms bonded to nitrogen in intermediates 3a-c increases sufficiently to protonate the nitrogen atom of the carbodiimide that subsequently would be activated to accept the nucleophilic attack of the resulting anilide anion or aniline (see Scheme 4). This mechanism would be similar to that accepted for peptide-bond formation mediated by carbodiimides [23][24][25][26]. It can also be possible that these two steps, i.e., protonation and nucleophilic attack occur in a quasi-concerted manner around the intermediates 6a-c.
\n\nConclusion\nIn conclusion, we show the possibility to isolate and characterize palladium complexes by performing some reactions using large amounts of palladium salts. The structures of these complexes shed light onto the reaction mechanism of the palladiumcatalyzed reaction. In this case, we have applied this methodology to isolate and characterize bis(anilino)-and bis(guanidino)palladium complexes that are proposed to be reaction intermediates, together with the still not isolated aniline-carbodiimide palladium complex 6, in the mechanism of the guanylation of anilines. Our study opens the way to apply a similar methodology to study the reaction mechanism of other catalytic reactions.
", "answer": "In the context of palladium-catalyzed guanylation of anilines herein, we have been able to characterize and isolate bis(anilino) and bis(guanidino)Pd(II) complexes using reaction conditions under which stoichiometric amounts of palladium salts are used. Characterization of these palladium complexes strongly supports a mechanistic proposal for the catalytic guanylation of anilines using PdCl 2 (NCCH 3 ) 2 as catalyst that involves the intermediacy of these Pd(II) complexes.", "id": 639} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nanterior cervical discectomy and fusion is a commonly performed surgery for the treatment of spondylosis , radiculopathy , myelopathy , and trauma .\nesophageal perforation is an exceedingly rare complication following anterior cervical discectomy and fusion ( acdf ) .\nthe incidence of these complications ranges from 0.02 to 1.52% although is higher when it is a result of trauma . we describe a case of a 24-year - old man who underwent acdf and corpectomy following a motor vehicle accident who developed delayed onset aspiration pneumonia and dysphagia requiring surgical repair of an esophageal perforation . to the best of our knowledge\nthere has been no prior literature discussing airway management in patients who underwent esophageal repair for perforation following cervical spine surgery .\nwe believe this paper will provide a deeper understanding to the intensivist in regards to postoperative airway management in this type of patient .\na 24-year - old man presented to an outside hospital following a motor vehicle accident with cervical spine fractures of c5 - c7 , anterolisthesis of c6 and associated spinal cord transection with resulting quadriplegia .\nthe patient was taken to the operating room and underwent anterior cervical decompression and fusion ( acdf ) of c5 - 7 , c6 corpectomy with polyetheretherketone ( peek ) cage and c4 - t1 posterior fusion [ figure 1a ] .\npostoperatively the patient did well and was discharged to a rehabilitation center at our institution .\nlateral cervical x - ray shows c4-t1 posterior fusion with c5-c7 acdf and peek cage at the level of c6 with no apparent hardware defects ( a ) ct neck demonstrated air surrounding the implant at c6 as well as the anterior fusion plate ( b ) barium swallow study showed a posterior esophageal barium leak at c5-c6 and a te - fistula .\nthe contents of the fistula are seen tracking inferiorly t1 and is seen anterior to the fusion plate ( c ) barium swallow study done ten days postoperatively shows resolution of perforation ( d ) approximately four months following his surgeries the patient began to develop increased sputum production , cough and fever .\n, the aspiration was thought to be due to the patient 's poor pulmonary clearance from his immobility and quadriplegia . while on antibiotic therapy for aspiration pneumonia the patient developed acute dysphagia .\ncomputed tomography ( ct ) scan demonstrated air surrounding the implant at c6 as well as the anterior fusion plate [ figure 1b ] .\nbarium swallow revealed an esophageal defect with contrast tracking down the prevertebral space to the level of t1 anterior to the cervical fusion plate as well as a tracheo - esophageal fistula [ figure 1c ] .\nthe patient underwent removal of the anterior plate , which was visualized in the pharyngoesophagus during intraoperative video - assisted laryngoscopy , removal of peek cage and placement of antibiotic impregnated bone cement , primary repair in conjunction with a sternocleidomastoid muscle flap being placed on the esophageal defect [ figure 2 ] .\npostoperatively , the patient remained intubated with the ngt to remain in place for one week .\nthe patient was extubated over a soft 22-french exchange catheter without incident and repeat barium swallow study demonstrated resolution of the esophageal perforation [ figure 1d ] .\nanterior cervical discectomy and fusion ( acdf ) has been the mainstay treatment of patients with radiculopathy or myelopathy attributed to cervical spine disease , particularly herniated nucleus pulposus . in the trauma\nsetting , vertebral body fracture may require corpectomy in which acdf is typically performed in conjunction with posterior instrumentation .\nesophageal perforation is a more rare and potentially life threatening complication occurring in 0.02 - 1.52% of patients .\nidentifying patients with esophageal perforation can be difficult as the clinical presentation and initial onset is highly variable .\npresentation with dysphagia , choking , aspiration , pain , fever or subcutaneous emphysema can all be postoperative complaints typically seen in up to 9.5% of patients .\nthe placement of an anterior cervical plate improves fusion rates and reduces risk of graft migration .\nadditionally , chronic compression of the esophagus against the anterior cervical plate during swallowing can result in pressure necrosis and eventually perforation and fistula formation .\ndiagnosis of esophageal perforation can be challenging due to the delayed and variable clinical presentation .\nin addition to computed tomography ( ct ) scan , upper endoscopy , barium contrast studies , and bronchoscopy are the most informative studies to determine the location and extent of perforation . proper management of esophageal perforation is very important as its associated mortality rate is high . a conservative approach including nil per os ( npo ) , with temporal parenteral nutrition by either ng or peg tube and broad - spectrum intravenous antibiotics may be appropriate in a very select group of patients where perforation is incidentally found and are asymptomatic .\nspontaneous healing of these injuries may take four to twelve weeks however , this conservative approach is associated with a 20 - 45% rate of abscess formation .\nthe use of a sternocleidomastoid ( scm ) muscle flap has been considered the gold standard to achieve and maintain perforation closure as without it esophageal sutures will invariably fail .\nthe scm is a highly mobile and vascularized medium that can improve antibiotic delivery , wound healing and provides a physical barrier between the esophagus and the cervical spine .\nimportant considerations when extubating is the degree of healing following esophageal perforation repair , mallampati grade , as well as the possible need and risks of reintubation in an airway emergency . although most reports describe waiting approximately 10 - 14 days postoperatively before resuming oral feeds , our patient was successfully extubated and tolerated oral feeds suggesting this period of time to be sufficient for would healing . in our patient ,\nalthough rare , esophageal perforation can occur following accidental esophageal intubation and is of clear concern in patients who underwent esophageal repair .\nrisk of perforation is higher when inexperienced individuals attempt intubation , difficult intubation requiring multiple attempts , as well as in emergency scenarios . when the patient has satisfied all weaning parameters and has a present cuff leak we strongly recommend that an experienced anesthesiologist be present for extubation and have all appropriate airway devices available including a fiberoptic bronchoscope .\nthe more rigid and thicker bougie should be avoided due to their risk of trauma .\na small hole should be made in the facemask such that the exchange catheter may pass through while the patient receives 8 - 10 l of oxygen for typically 30 - 60 minutes .\nthis will allow for a more controlled and safer reintubation in the event the patient fails extubation and therefore reduce the potential risk of reperforation .\ngreater vigilance is required in the event reintubation is required as perforation of the surgical repair site is of great concern .\ntherefore , it is our recommendation that an experienced anesthesiologist be present for extubation and that all appropriate airway devices are available including a fiberoptic bronchoscope .", "answer": "anterior cervical discectomy and fusion ( acdf ) is a commonly performed surgery for the treatment of spondylosis , radiculopathy , myelopathy , and trauma to the cervical spine . \n esophageal perforation is a rare yet serious complication following acdf with an incidence of 0.02 to 1.52% . \n we describe a case of a 24-year - old man who underwent acdf and corpectomy following a motor vehicle accident who subsequently developed delayed onset esophageal perforation requiring surgical intervention . \n we believe that the detailed review of the surgical management of esophageal perforation following cervical spine surgery will provide a deeper understanding for the intensivist in regards to postoperative airway management in these types of patients . \n careful extubation over a soft flexible exchange catheter should take place to help reduce the risk of perforation in the event reintubation is required .", "id": 640} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 35-year - old female presented with a painless , slowly growing \n mass in the right inferior orbit for the past four years .\nshe did \n not complain of diminution of visual acuity , diplopia or field \n defect . on examination , visual acuity in both eyes\nthe right side demonstrated a solid , non - tender , \n freely mobile mass in the inferior orbit , which became more \n prominent on applying pressure on the upper part of the globe . \n\nthe mass measured approximately 20 mm 15 mm and the \n size did not vary with valsalva maneuver , ocular movements \n or posture .\nslit - lamp \n and fundus examination of the eye showed normal anterior \n and posterior segments .\nb - scan ultrasonography revealed an extraconal , \n homogenous lesion in the inferior part of the right orbit . \n\ncomputed tomography revealed a non - enhancing well- \n defined homogenous mass measuring 20 mm 12 mm in the \n right inferior orbit which was displacing the inferior rectus \n and inferior oblique muscle upwards .\nthe mass was separate \n from the above - mentioned muscles and produced no globe \n indentation or displacement [ figure 1a ] .\na provisional diagnosis of orbital dermoid was made and \n the patient was taken up for an excision biopsy .\nperoperative findings were of a smooth , well - encapsulated \n mass with no attachments to the surrounding muscles .\non histopathological examination , the gross specimen \n consisted of a smooth well - encapsulated solid mass measuring \n 25 mm in the greatest diameter [ figure 1b ] .\nmicroscopically , a \n biphasic pattern of tumor cells was seen with areas of closely \n packed spindle cells having fusiform nuclei and eosinophilic \n cytoplasm ( antoni a ) admixed with looser myxoid tissue \n having ovoid cells ( antoni b ) . at places ,\nthese tumors cells \n were arranged in palisades and this arrangement of cells \n is referred to as verocay bodies .\norbital \n schwannoma is a tumor of adulthood usually presenting \n between 20 to 70 years of age .\nschwannomas are usually \n asymptomatic when small and may produce progressive , \n painless proptosis on enlargement\n. a variable combination \n of signs and symptoms may be present due to the variable \n origin and location of the tumor in the orbit.2 displacement \n of the globe is related to the site of the tumor mass .\nmost \n schwannomas arise from branches of either the supraorbital \n or supratrochlear nerves and hence produce downward \n displacement of the globe .\nless commonly , the tumor may arise \n from the infraorbital nerve and produce upward displacement \n of globe .\nlarger tumors may produce diplopia , particularly \n when they arise from the orbital portion of the third , fourth \n or sixth nerve .\nthe growth of the tumor may \n cause compression of the optic nerve with papilledema or \n optic atrophy .\nsurgical excision is the treatment of choice and \n the tumor should be removed intact at the earliest to prevent \n compression of the optic nerve.3 incomplete excision can lead \n to recurrence or even intracranial extension .\nhighly cellular \n tumors have greater chance of recurrence and malignant \n transformation . therefore an early treatment is indicated \n to avoid the complications related to progressive growth of \n the tumor . in our patient , we were successful in achieving \n the above objectives with timely and complete excision of \n the tumor .\norbital schwannoma arising from the infraorbital nerve \n is rare and clinical diagnosis is often difficult .\nextensive \n literature search revealed only a few case reports of an orbital \n schwannoma arising from the infraorbital nerve.4 - 10 our \n patient presented with the tumor in this uncommon location . \n\na solitary schwannoma , though rare , should be considered \n as a preoperative differential diagnosis of a unilateral slow- \n growing orbital mass in an adult and prompt management \n is warranted to prevent development of vision - threatening \n complications .", "answer": "a rare case of unilateral orbital schwannoma arising from the \n infraorbital nerve is presented . \n an excision biopsy with complete \n removal of the mass in the inferior orbit was performed . \n a \n definitive diagnosis was made on histopathological examination . \n \n the clinical and histological features of schwannoma are \n discussed . a need for early removal of such tumors \n is \n recommended to prevent complications .", "id": 641} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin canada , fish contribute to over 50% of the dietary intake of mercury ( hg ) by adults ( dabeka et al .\n2003 ) , and fish containing the highest concentrations of hg are predatory fish , such as shark , swordfish and tuna ( health canada 2007 ) .\nhg , present in fish as both methyl - hg and inorganic hg , is a potent neurotoxicant . on the other hand , fish are one of the best food sources of vitamin d and omega-3 fatty acids , dha and epa , and it is important to weigh the benefits of eating fish against the potential toxicity of hg present in the fish ( health canada 2007 ) . to promote consumption of fish while at the same time providing advice to vulnerable population groups about limiting consumption of predatory fish , and to evaluate the risk - to - benefit ratio of eating fish , it is important to know the levels of hg in predatory fish sold at the retail level in canada . in 2002 ,\n2004 ) which found that predatory fish , such as shark , swordfish and tuna , contained high concentrations of hg , averaging 1820 ng g for shark , 1430 ng g for marlin and 930 ng g for fresh or frozen tuna .\nthis survey is a supplement to the previous work and provides levels of hg found in retail fish purchased in 2005 .\nmarlin , sea bass , red snapper , orange roughy , fresh water trout , grouper , black cod ( sablefish ) , arctic char , king fish ( king mackerel ) and tilefish are included in this survey .\n, samples were purchased as cleaned fillets or whole fish at the retail level in toronto , vancouver and montreal in 2005 .\nthe retail stores included four supermarket chains and four specialty fish seafood outlets in each city .\neach sample was shipped frozen to maxxam analytics inc . for cleaning ( if necessary ) , homogenization and bottling in pre - cleaned polyethylene bottles supplied for total hg and glass jars with teflon cap liners for methyl hg ( i - chem brand , thermo fisher scientific ) .\nthe samples were then frozen and shipped to health canada 's food research division in ottawa for analysis .\ninformation provided with each sample included , where available , the species name as provided by the retail outlet , the state of the sample when purchased ( frozen , fresh or previously frozen ) , the city of sample pickup , name of store where purchased , country of origin and date of collection .\nthe countries of origin for the samples were usa ( 7 ) , argentina ( 1 ) , australia ( 5 ) , canada ( 26 ) , chile ( 13 ) , hungary ( 2 ) , mexico ( 1 ) , new zealand ( 3 ) and taiwan ( 1 ) , with the remaining samples being of unknown origin .\nanalyses were performed using the reagents , instrumentation and methodology described in dabeka et al .\nbriefly , after a low - temperature nitric / hydrochloric acid and hydrogen peroxide digestion of roughly 1 g fish tissue and dilution to 50 ml with water , measurements were made using a cetac-6000a dedicated hg analyser equipped with an asx-500 autosampler and adx autodilutor .\nquality control measures for each analytical batch included three reagent blanks , two reagent blank spikes ( 200 ng hg ) , one sample spike of 400 ng hg ( in duplicate for both the unspiked and spiked 400 ng sample ) and duplicates of three different standard reference materials ( srms ) with certified hg concentrations .\ntwo cross - check standards ( from a different manufacturer ) were included in each batch for standard verification during the run .\nthe solution limit of detection ( lod ) was estimated for each analytical batch by multiplying the standard deviation of the three reagent blanks by 3 .\nsample lods were calculated by multiplying the solution lod by the dilution volume and dividing by the weight of the actual sample taken for analysis .\nsolution lods averaged 0.045 ng ml and sample lods averaged 1.9 ng g. recoveries from spiked blanks and samples averaged 97 and 101% , respectively .\none of the sample spike recoveries was high ( 155% in batch 8) , and this was due to the high concentration of hg in the sample selected for spiking in the batch compared with the spike added .\nagreement with certified levels in the national research council of canada ( nrcc ) dolt-2 and dorm-2 srms and the national institute of standards and technology ( nist ) oyster tissue 1566a srm was generally satisfactory , although results for batches 9 , 10 and 11 were unusually high .\nblank spaces in the tables denote that the particular test was not included in the batch .\nnote : blank spaces denote that the particular test was not included in the batch .\n, samples were purchased as cleaned fillets or whole fish at the retail level in toronto , vancouver and montreal in 2005 .\nthe retail stores included four supermarket chains and four specialty fish seafood outlets in each city .\neach sample was shipped frozen to maxxam analytics inc . for cleaning ( if necessary ) , homogenization and bottling in pre - cleaned polyethylene bottles supplied for total hg and glass jars with teflon cap liners for methyl hg ( i - chem brand , thermo fisher scientific ) .\nthe samples were then frozen and shipped to health canada 's food research division in ottawa for analysis .\ninformation provided with each sample included , where available , the species name as provided by the retail outlet , the state of the sample when purchased ( frozen , fresh or previously frozen ) , the city of sample pickup , name of store where purchased , country of origin and date of collection .\nthe countries of origin for the samples were usa ( 7 ) , argentina ( 1 ) , australia ( 5 ) , canada ( 26 ) , chile ( 13 ) , hungary ( 2 ) , mexico ( 1 ) , new zealand ( 3 ) and taiwan ( 1 ) , with the remaining samples being of unknown origin .\nanalyses were performed using the reagents , instrumentation and methodology described in dabeka et al .\n( 2002 ) . briefly , after a low - temperature nitric / hydrochloric acid and hydrogen peroxide digestion of roughly 1 g fish tissue and dilution to 50 ml with water , measurements were made using a cetac-6000a dedicated hg analyser equipped with an asx-500 autosampler and adx autodilutor .\nquality control measures for each analytical batch included three reagent blanks , two reagent blank spikes ( 200 ng hg ) , one sample spike of 400 ng hg ( in duplicate for both the unspiked and spiked 400 ng sample ) and duplicates of three different standard reference materials ( srms ) with certified hg concentrations .\ntwo cross - check standards ( from a different manufacturer ) were included in each batch for standard verification during the run .\nthe solution limit of detection ( lod ) was estimated for each analytical batch by multiplying the standard deviation of the three reagent blanks by 3 .\nsample lods were calculated by multiplying the solution lod by the dilution volume and dividing by the weight of the actual sample taken for analysis .\nsolution lods averaged 0.045 ng ml and sample lods averaged 1.9 ng g. recoveries from spiked blanks and samples averaged 97 and 101% , respectively .\none of the sample spike recoveries was high ( 155% in batch 8) , and this was due to the high concentration of hg in the sample selected for spiking in the batch compared with the spike added .\nagreement with certified levels in the national research council of canada ( nrcc ) dolt-2 and dorm-2 srms and the national institute of standards and technology ( nist ) oyster tissue 1566a srm was generally satisfactory , although results for batches 9 , 10 and 11 were unusually high .\nblank spaces in the tables denote that the particular test was not included in the batch .\nnote : blank spaces denote that the particular test was not included in the batch .\na summary of the results ( table 2 ) found that arctic char , red snapper and fresh water trout contained the lowest concentrations of hg , averaging 37 , 148 and 55 ng g , respectively .\naverage levels in the other fish types varied from 384 ng g for black cod to 854 ng g for marlin .\nnote : designated fish subject to a 1000 ngg regulatory limit , others to a limit of 500 ngg average concentrations of hg in the different species were in general agreement with those found in other canadian and international surveys ( table 3 ) .\ndifferences among the surveys can be attributed to the size of the individual fish from which the sample was taken , as fish mercury concentrations vary directly with fish size .\nadditionally , regional differences in hg concentrations may be a function of the food source .\nfor example , tilefish caught in the atlantic ocean contained 144 ng g hg , whereas those sampled in the gulf of mexico averaged 1450 ng g ( fda 2009 ) .\nit is uncertain whether this difference is due to different food sources or to the situation that the tilefish in the two areas are different species .\ncomparison of hg levels ( ngg ) found in this study with those found previously in canada and other countries .\naverage of three tilefish - two samples purchased in 2008 containing 128 and 3000 ng g , and one purchased in 2005 contained 80 ng g. fda ( 2009 ) ; environmental protection agency ( 2000 ) ; national marine fisheries service ( 1978 ) .\nthe primary reference for the gulf tilefish and sablefish data in the fda report is a national marine fisheries service report ( hall et al .\n1978 ) , while that for the kingfish or king mackerel is an epa report ( ache et al .\n144 ng g in atlantic tilefish and 1450 ng g in those caught in the gulf of mexico ( fda 2009 ) .\nthe current canadian regulatory limit for total mercury in the edible portion of commercially sold fish is 500 ng g , with the exception of a 1000 ng g limit and accompanying consumption advice ( health canada , 2008 ) for specific species of piscivorous fish : shark , swordfish , marlin , orange roughy , escolar , and fresh and frozen tuna ( health canada , 2010 ) .\nthe proportion of individual samples exceeding the relevant standards was : 13% of black cod , 24% of grouper , 40% of king fish , 28% of marlin , 20% of sea bass and 50% ) of tile fish ( table 2 ) .\nhowever , the uncertainty in these percentages is high due to the small numbers of each species tested . the mean and\nmedian concentrations of mercury in black cod , grouper , king fish , marlin and sea bass were all below the standards for the respective species .\nadditional data would aid in characterizing the typical mercury concentrations in some types of fish , in particular king fish and tilefish .\nfor example , the us fda has reported a median mercury value in tilefish ( atlantic ) of only 99 ng g ( n = 32 ) ( fda , 2009 ) .\nit should also be noted that the occasional consumption of infrequently consumed fish containing mercury levels greater than the regulatory limits would not be expected to pose a health risk to consumers .\nthanks are due to elizabeth elliott and mark feeley of the chemical health hazard assessment division , bureau of chemical safety for review and helpful suggestions .", "answer": "total mercury was analysed in 188 samples of predatory fish purchased at the retail level in canada in 2005 . \n the average concentrations ( ng g1 , range ) were : sea bass 329 ( 381367 ) , red snapper 148 ( 36431 ) , orange roughy 543 ( 279974 ) , fresh water trout 55 ( 20430 ) , grouper 360 ( 81060 ) , black cod 284 ( 71651 ) , arctic char 37 ( 2854 ) , king fish 440 ( 42923 ) , tilefish 601 ( 791164 ) and marlin 854 ( 1252346 ) . \n the canadian standard for maximum total mercury allowed in the edible portions of fish sold at the retail level is 1000 ng g1 for shark , swordfish , marlin , orange roughy , escolar and both fresh and frozen tuna . \n the standard is 500 ng g1 for all other types of fish . in this study , despite the small number of samples of each species , the 1000 ng g1 maximum was exceeded in five samples of marlin ( 28% ) . \n the 500 ng g1 maximum was exceeded by six samples of sea bass ( 20% ) , four of tilefish ( 50% ) , five of grouper ( 24% ) , six of king fish ( 40% ) and one of black cod ( 13% ) ,", "id": 642} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmutations in codons 12 and 13 of kirsten rat sarcoma viral oncogene homolog ( kras ) and b - raf murine sarcoma viral oncogene homolog b1 ( braf ) genes are frequently present in tumors of patients with metastatic colorectal cancer ( crc ) ; they are observed in 30 - 45% and 5 - 20% of cases respectively 1 .\nless commonly detected crc tumor mutations are codon 61 , 146 of the kras oncogene , and at other sites in the braf gene .\nkras and braf mutations have been frequently described as mutually exclusive in crc , in that tumors usually have neither , or only one , of these specific mutations .\nrarely patients may have crc with coincident kras and braf mutations ; herein we report three such cases and review of the literature .\nalthough highly uncommon , identification of this dual tumor genotype is important , as current clinical trials are being designed enriching for patients whose tumors harbor either a kras or braf mutation , but haven't addressed those patients with coincident kras and braf mutations . due to the infrequent rate of coincident mutation , it is not known if these patients have a tumor biology distinct from kras or braf mutant tumors .\nunder an institutional review board approved retrospective chart review protocol ( dr-11 - 0113 ) , we reviewed samples tested at a clinical laboratory for tumor kras and/or braf mutations from 2008 - 2011 .\ndna was extracted from microdissected paraffin - embedded tumor and analyzed by a polymerase chain reaction ( pcr)-based dna sequencing method to examine codons 12 , 13 and 61 of the kras proto - oncogene .\nthe sensitivity of detection of this assay is approximately 1 in 10 mutation - bearing cells in microdissected area .\ndna was also analyzed by pcr and a pyrosequencing method for codons 595 to 600 of exon 16 of braf oncogene ; the methods for these assays have been described elsewhere 2 .\na total 6,633 crc patient tumors were screened for mutation analyses and of those 1,483 case were tested for both kras and braf mutations .\n644 were kras - mutant ( 43% ) and 3 ( 0.2% ) of these were bearing a concomitant braf ( v600e ) mutation .\nthe first patient is a 65 year - old woman who presented with small bowel obstruction .\nthe patient underwent a biopsy of the metastatic liver lesion that was sent for kras mutation and braf mutation analysis ; a tumor mutation was detected in codon 12 ( ggt to gat ) of the kras gene that would change the encoding amino acid from glycine to aspartic acid ( g12d ) and codon 600 ( gtg to gag ) in exon 15 of the braf gene that would change the encoding amino acid from valine to glutamine ( v600e ) .\nthe second case identified was a 72 year - old woman with rectal cancer metastatic to the lungs ; similar tumor mutations were detected in kras ( g12d ) and braf ( v600e ) proto - oncogenes . in both cases\nthe tumors were microsatellite stable ; concomitant braf and kras mutations were not identified among patients samples ' whose tumors were microsatellite instable .\nthe third case is 51 year - old man who presented with abdominal pain and was found to have a descending colon cancer with liver metastasis . in specimen from liver lesion ,\ncoincident kras and braf mutations appear to be rare entity ( present in 3 out of over 1,928 samples tested ) . due to the infrequent observation of this phenomena , it is not clear whether or not these tumors have a different biology and natural history than kras or braf mutant tumors , or which of the two mutations is the dominant oncogene driving tumor proliferation .\na prior study has demonstrated that concomitant tumor mutations have been relatively frequently observed human crc cell line ; in this study , of 24 human crc cell lines , one cell line ( gp2d ) demonstrated mutations in both kras and braf oncogenes ( however the braf mutation was in the less frequently observed at the codon 529 site ) 3 . in an analysis of 250 patients tumor specimens with microsatellite stable disease , kras mutations were identified in 45.2% of primary tumors , and that concomitant kras and braf mutations were found in 10 lymph nodes ( 35.7% ) from a total 28 samples whereas only 3 of primary tumor with negative lymph nodes were positive for coincident mutation ( 2.3%)4 . there was also noted to be a higher proportion of concomitant mutations based on the degree of transmural penetration of the tumor ; 1/36 ( 2.8% ) for t2 tumors and 3/32 ( 9.4% ) for t4 tumors , suggesting activation of both genes is associated with progression of disease .\nsince kras mutation testing became standard - of - care for determining lack of treatment efficacy with antibody anti - epidermal growth factor ( egfr ) monoclonal antibody therapy in patients with advanced crc , large studies involving kras and braf mutation analysis crc screenings have been undertaken ; the results of studies with over 200 patients is demonstrated in table 1 .\nunlike study by olivera et al 4 , all of these large data sets demonstrated that in crc kras and braf mutations were mutually exclusive , except in one case 5 .\nin one other series , two patients had tumors with two distinct kras mutations 6 .\nmolecular profiling demonstrates that kras and braf mutant tumors have very different gene signatures suggesting different signaling pathways are activated 12 .\nin addition early data suggest outcomes with the use of anti - egfr monoclonal antibody therapy appear to be different depending on the site of kras mutation 13 . at this time\nit is not known which gene expression profile pattern of concomitant kras and braf tumors is , and whether it more represents a kras tumor gene signature or braf signature .\ngiven fact of tumor heterogeneity and the large variety of mutations observed in this disease , as well as epigenetic changes observed , it is likely that in the future , tumor gene expression profiling will provide a better indication of the activation of tumor signaling , and be a better biomarker of treatment efficacy .\nstrengths of our study are screened large patient population and available detailed clinical and pathological information .\nthe main limitation , however , were retrospective nature of study and possible artefactual mutation detection .\nfurther multi - center prospective studies are necessary to understand true frequency and the role concomitant kras and braf mutations .\nconcomitant kras and braf tumor mutations are rare enough to be considered virtually ( albeit not entirely ) mutually exclusive .\nsince kras and microsatellite instability analysis are the only validated negative biomarkers of therapy efficacy in crc , routine analysis for braf mutations in kras wild type tumors is not recommended .\nhowever if patients are being considered for clinical trial , especially those in which the eligibility require the presence of a kras mutation , braf mutation analysis would be highly advisable .\nfuture enriched clinical trials for kras or braf should specifically address eligibility of patients whose tumors harbor a concomitant kras and braf mutation .", "answer": "kras mutations occur frequently in colorectal cancers ( crc ) and predict lack of response to anti - epidermal growth factor receptor ( egfr ) monoclonal antibody therapy . \n crc braf mutations , most commonly at v600e , occur less than 10% of the time , and occur usually in kras wild - type tumors , and more frequently in microsatellite instable tumors . \n concomitant kras and braf mutant crcs are rare ( occurring in 0.001% ) ; braf mutations should not be routinely tested in patients with kras mutant tumors , unless the patients is participating in a clinical trial enriching for the presence of a kras or braf tumor . \n clinical trials treating patients with either kras or braf mutant tumors should address eligibility of patients with concomitant kras and braf mutations .", "id": 643} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nretinitis pigmentosa ( rp ) was defined as a group of hereditary disorders that diffusely involve photoreceptor and pigment epithelial function characterized by progressive visual field loss and abnormal electroretinogram .\nrp also has changes at vitreoretinal interface , such as vitreoretinal traction and preretinal membrane , which causes macular disorders such as cystoids macular edema and macular hole .\nwe report a case of vitreoretinal traction syndrome associated with rp , which spontaneously resolved after posterior vitreous detachment ( pvd ) .\na 81-year - old woman presented with bilateral loss of peripheral vision and defective dark adaptation 15 years before .\nthe best - corrected visual acuity was 20/28 and 20/28 in the right and left eyes , respectively .\nslit - lamp examination showed bilateral retinal arteriolar narrowing and intraretinal pigment deposition ( bone spicule pigmentation ) in both eyes ( figure 1a ) .\nthe visual fields of the patient were markedly constricted to the central 10 in both eyes ( figure 2 ) .\non june 2 , 2006 , retinal detachment was detected in the nasal periphery in the right eye ( figures 1b and 1c ) . at that time , pvd was confirmed with weiss ring ( figure 3 ) .\nfluorescein angiography showed a hyperfluorescence due to atrophy of retinal pigment epithelium but no active leakage in the detached area ( figure 1c ) .\nthe detached area was within the area where the visual field was lost , and we observed a clinical course of this eye without any treatment . retinal detachment was kept localized and not extended .\nfive months later , pvd further progressed beyond the arcade area , accompanying retinal hemorrhage around the detached retina .\nin this case , an eye with rp was complicated with tractional retinal detachment , possibly associated with increased vitreoretinal traction secondary to the incidence of pvd .\nthe retinal detachment was limited within the area where the visual field was lost and was not progressive .\neight months later , spontaneous resolution of tractional retinal detachment resulted from progression of pvd , which was suggested by transiently increased traction - related retinal hemorrhage .\neyes with rp may have abnormal liquefaction of vitreous and altered distribution of vitreoretinal adhesion .\nthe incidence of pvd in the posterior pole might result in the focal remarkable traction in the peripheral retina and tractional retinal detachment .\neight months later , the retinal detachment was resolved because local vitreoretinal traction was weakened with extention of pvd beyond the arcade vessels .\nrp has vitreomacular traction - related pathologic events involving vitreomacular traction syndrome , cystoids macular edema , and macular hole.13 such changes in this patient with rp might result in a tractional retinal detachment .\nrani et al4 reported that a 50-year - old man underwent a tractional retinal detachment involving the posterior pole with a taut posterior hyaloids surface . in this study ,\nvitrectomy was not performed because the patient opted for no surgical intervention in view of poor prognosis . on the other hand ,\nit was reported that vitrectomy was effective for vitreous opacity,5 cystoid macular edema,6 exudative retinal detachment,7 and macular holes8 in rp . however , regarding the indication to perform a vitrectomy , the balance of the expected gain in visual function and usual risks of vitrectomy and rp - related risks , such as phototoxicity worsening of visual field loss , and cystoid macular edema .\nit might be a choice that a patient with tractional retinal detachment in rp is observed without surgical treatment , if the detached area is not progressive .", "answer": "we present a case of retinitis pigmentosa with vitreoretinal traction - associated retinal detachment . \n the retinal detachment was detected in the nasal periphery . \n no retinal breaks and no active vascular leakage were observed by fundus scopy and fluorescein angiography , respectively . \n however , 8 months later , the tractional retinal detachment was spontaneously resolved with posterior vitreous detachment .", "id": 644} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nCell surface display yields evolvable, clickable antibody fragments\n\nPaper sections:\n\nThe introduction of non-canonical amino acids (ncAAs) into recombinant proteins enables enhancement or alteration of protein function.[1,2] Replacement of canonical amino acids by ncAAs, in response to either sense codons or nonsense codons, can lead to marked changes in reactivity, stability, and other properties.[3\u20139] In either case, introduction of ncAAs may lead either to loss of protein function or to beneficial changes in behavior. High-throughput screening methods and directed evolution[10,11] can be used to isolate ncAA-modified protein variants with novel and desirable characteristics.
Here we present a cell surface display method for evolving binding proteins that contain reactive, \"clickable\" ncAAs. Specifically, we replace the methionine (Met; 1; Figure 1A) residues in single chain variable fragment (scFv) mutants of the anti-digoxigenin 26-10 antibody[12] with the Met surrogates homopropargylglycine (Hpg; 2), azidohomoalanine (Aha; 3) or norleucine (Nrl; 4). The display platform[13,14] enables identification of variants with improved expression levels, solubility, and antigen-binding properties. Several of the isolated Aha variants exhibit improved binding kinetics relative to their Met counterparts, and the azide side chains of Aha can be chemically modified under mild conditions without affecting binding function. Antigen binding and protein modification can be investigated concurrently for scFvs displayed on the E. coli cell surface.
We first used flow cytometry to investigate the function of the 26-10 anti-digoxigenin scFv displayed on the surface of E. coli cells in the Lpp-OmpA' display system (see Supporting Information for display details).[13,14]ScFv function was assessed in multiple amino acid contexts using BODIPY FL digoxigenin 5 as a probe of binding behavior (Figure 1). Cells displaying the Met form of the scFv could be readily labeled with 5 (Figure 1B), while cells displaying the Hpg form exhibited low fluorescence levels (Figure 1C). Fluorescence levels of cells displaying the Aha-substituted scFv were reduced relative to the cells expressed in Met (Figure 1D), while cells displaying the Nrl-substituted construct exhibited unchanged fluorescence levels (Figure 1E).
The loss of function of the Hpg form of the scFv led us to investigate whether point mutations could enable recovery of digoxigenin binding. We developed an error-prone PCR library (Library 1) in which the antibody fragment and the majority of the display anchor were subjected to mutation. In the first round of sorting, Library 1 was expressed and sorted under conditions leading to partial substitution of Hpg for Met (Figure S1).[15] Sorting this population led to enrichment of clones exhibiting Hpg tolerance. Using expression conditions leading to near-complete replacement of Met, the Hpg-tolerant population was further enriched for functional clones in two additional rounds of sorting (Figure S1).
Individual clones from the thrice-sorted Library 1 were isolated, tested for their ability to bind antigen when expressed in Hpg form on the E. coli cell surface, and sequenced. All ten clones bound 5 when Met was replaced with Hpg, and each variant contained at least one amino acid mutation in the scFv (Table S1). While some display-anchor mutations were identified during screening of Library 1 and Library 2 (see below), none appeared to affect scFv properties in any significant way. We performed additional analysis of Mut2, a clone recovered from five of the ten colonies (Figure 1, Table 1, Table S1). In flow cytometry experiments, cells displaying Mut2 bound more 5 than cells displaying the parent 26-10 scFv, irrespective of whether the scFv was expressed in its Met, Hpg, Aha or Nrl forms. The effect was most striking for the Hpg and Aha forms of the protein (Figure 1G, H).
Seeking to improve the binding behavior of the scFv in multiple ncAA contexts, we prepared Library 2 from DNA isolated from thrice-sorted Library 1 via error-prone PCR, and attempted to isolate variants with improved binding after replacing Met with ncAAs. Four rounds of sorting under increasingly stringent conditions were performed, using kinetic competitions in the last two rounds to isolate clones with the lowest off rates (Figure S2, Table S2).[16] Individual clones were picked after three (Hpg and Aha contexts) and four (Hpg, Aha, and Nrl contexts) rounds of enrichment, sequenced (Table S3), and subjected to on-cell off-rate measurement (Table S4).[16] Most clones exhibited off rates equal to or lower than the off rates of the parent construct or Mut2 when expressed in the same amino acid context.
We examined the sequences of individual clones and the sorted populations in detail (Table 1, Figure 2, Table S5). Mutations at Met codons were common; the Met residues at positions H20 and H80 (Kabat numbering) were replaced in the majority of variants. On the other hand, the Met residues at positions H34 and H100B were conserved. The preservation of M(H100B) is especially striking in view of the fact that it is in direct contact with the antigen.[12] The data also reveal the frequent addition of a Met codon at position H82C; Met replaces a leucine at this position in more than 50% of all sequenced variants. Of the mutations not involving Met, S(H24)F, S(H24)Y, and F(H29)S occurred most frequently. Quantitation of mutational frequencies in the different populations indicated that ncAA context changes mutational frequency only modestly (Table S5).
We produced and characterized several antibody fragments in soluble form. Each scFv of interest was produced in its Met form and in the ncAA form in which it was isolated. In addition, attempts were made to produce the parent 26-10 scFv and Mut2 in Met and all ncAA contexts. The parent construct could be expressed and purified only in its Met and Nrl forms, while Mut2 could be expressed and purified in all four forms. MALDImass spectrometry indicated replacement of 80\u201393% of Met by the ncAA in each isolated variant (Table S6, S7). Table 1 and Figure 2 summarize the mutations found in the selected scFv variants.
Variation in the antigen-binding behavior of the variants was dominated by changes in koff, the dissociation rate constant. Surprisingly, the kinetic data indicate that replacement of Met by Aha in a given variant consistently decreased koff by a factor of two. Replacement of Met by Hpg increased koff by a factor of four, while replacement of Met by Nrl caused negligible changes in koff. It seems most likely that changes in koff are most sensitive to the identity of the residue at position H100B, which is in direct contact with the antigen.[12] Modest reductions in koff were achieved through further screening in both the Hpg and Nrl contexts, with the Hpg form of Hpg3x3 and the Nrl form of Nrl4x11 exhibiting two-fold lower dissociation rate constants as compared to Mut2 in the same ncAA contexts.
The Aha and Met forms of several scFv variants were subjected to strain-promoted azide-alkyne cycloaddition (SPAAC) with dibenzocyclooctyne dye 6 (Figure 3A, Figure S3). In-gel fluorescence experiments confirmed selective labeling of the Aha forms; minimal background labeling of the Met forms was detected. Mass spectrometry and the lower reactivity of the Aha form of Aha4x4 (which lacks Aha at H34) implicated position H34 as a major site of modification (Figure S4, Table S8). Our attempts to modify Hpg- and Aha-containing scFvs by the copper-catalyzed azide-alkyne cycloaddition were unsuccessful, possibly because of the limited surface accessibility of the reactive ncAA side chains in the proteins (Figure S5).[17]
SPAAC-modified scFv fragments retain antigen-binding behavior, as shown by western blotting assays. Samples for western blotting were prepared by adding digoxigenin-modified bovine serum albumin (BSA) in varying amounts to E. coli cell lysates. The samples were transferred to nitrocellulose membranes, and the membranes were probed with the Aha or Met forms of Aha4x5 fragments previously treated with 6. Scanning the membranes for fluorescence emission from 6 (Figure 3B) revealed that only the Aha form of the protein enabled detection of digoxigenin-modified BSA. To confirm that treatment with 6 did not adversely affect the Met form of the protein, the blots were further probed for the hexahistidine tags on the scFvs (Figure 3C). These experiments confirmed that both forms of Aha4x5 remained capable of binding to digoxigenin after SPAAC. Biacore assays further indicate that SPAAC conditions did not seriously alter antibody kinetic properties; kon values were reduced slightly, while koff values remained unchanged (Table S9).
We extended our functional analysis of tagged conjugates to scFvs displayed on the E. coli cell surface. We subjected E. coli cells displaying the Aha or Met forms of Aha4x5 to 16-hour labeling reactions with 7 (Figure 3D).[18,19] We then labeled the cells with 5 and streptavidin-phycoerythrin and performed flow cytometry. Cells displaying the Aha form of the scFv exhibited substantial fluorescence in both channels (Figure 3E), confirming that the Aha form of Aha4x5 retains binding function after chemical modification on the cell surface, while cells displaying the Met form bind 5 but exhibit low reactivity toward the cyclooctyne (Figure 3F). Additional experiments indicated that treatment of cells with unlabeled digoxin prior to treatment with 5 blocks the binding of 5 to scFvs regardless of chemical modification state (Figure S6). These experiments also revealed that some binding activity appears to be lost upon treatment of cells displaying the Aha form of Aha4x5 with 7; these losses in binding function may reflect an increase in crowding and steric hindrance on the surface of cells after treatment of 7 or denaturation of some scFvs during the click reaction. Finally, experiments verified that 7 reacts primarily with Aha side chains in scFvs, not Aha in other newly synthesized proteins; fluorescence values suggest that approximately 75 percent of 7 detected on the cell surface has reacted with displayed scFvs, with the remaining 25 percent reacting with other membrane proteins.
Having shown that both antigen-binding and modification of displayed scFvs can be monitored in a single flow cytometry experiment, we used a subset of samples to demonstrate the separation of various cellular populations via fluorescence-activated cell sorting (FACS). We mixed together cells exhibiting antigen binding only, chemical modification only, simultaneous binding and modification, and neither binding nor modification (Figure 4A). Four-way sorting of this mixture resulted in the recovery of clean populations exhibiting all combinations of binding and modification (Figure 4B\u2013E). These results suggest that this display platform should be amenable to simultaneous, high throughput evaluation and isolation of proteins based on chemical reactivity and binding function.
This work demonstrates how high-throughput screening of antibody fragments containing ncAAs can yield proteins with novel properties. The screening methods described here yielded scFvs with enhanced expression and antigen-binding behavior. Fragments containing Aha exhibited improved dissociation rate constants and susceptibility to chemical modification under mild conditions. These properties were demonstrated both in solution and on the E. coli cell surface. Our approach is complementary to the screening of libraries of antibody fragments via phage display with ncAAs[20] and to the introduction of reactive amino acids into antibody fragments site-specifically.[21] In the future, incorporating multiple ncAAs into recombinant proteins may enable re-design of antibody complementarity determining regions[22] with unconventional side chains to enhance molecular recognition. Cell surface-display of ncAA-modified proteins should also enable direct screening of libraries of chemically modified proteins of interest in the engineering of bi- or multivalent proteins,[23] switchable sensors,[24] or cyclized peptides.[25]
", "answer": "Non-canonical amino acids (ncAAs) provide powerful tools for engineering the chemical and physical properties of proteins. However, introducing ncAAs into proteins can affect protein properties in unpredictable ways, necessitating screening efforts to identify mutants with desirable properties. In this work, we describe an E. coli cell surface display platform for evolving clickable antibody fragments. This platform enabled isolation of antibody fragments with improved digoxigenin binding and modest affinity maturation in several different ncAA contexts. Azide-functionalized fragments exhibited improved binding kinetics relative to their methionine counterparts, facile chemical modification via the azide-alkyne cycloaddition, and retention of binding properties after modification. The results described here suggest new possibilities for protein engineering, including modulation of molecular recognition events by ncAAs and direct screening of libraries of chemically modified proteins.", "id": 645} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is characterised by the production of abnormal hb referred to as sickle hb or hbs.123 the prevalence of sca is high in sub - saharan africa with nigeria having the highest burden.45 sca has been associated with hyperhaemolysis , cerebrovascular disease , acute chest syndrome , vaso - occlusive crisis , pulmonary hypertension and premature death among others.67 relatively , individuals with sca enjoy a compensated state of ill health interspersed with periods of acute exacerbation characterised by hyperhaemolytic ( anaemic ) or vaso - occlusive ( voc ; painful crisis ) with infection , tissue hypoxia and micro - vascular occlusion as important predisposing events.68 abnormal lipid homeostasis has been reported in sca as well as other haematological disorders such as -thalassemia and this has been suggested to have the potential to alter membrane fluidity and function of red blood cell ( rbc ) in individuals with sca.91011 earlier studies reported significant increase in plasma triglyceride ( tg ) levels and concurrent significant decrease in plasma levels of total cholesterol ( tc ) , high - density lipoprotein - cholesterol ( hdl ) and low - density lipoprotein - cholesterol ( ldl ) in sca subjects.91112 several inconclusive mechanisms such as heightened erythropoiesis ( causing increased cholesterol utilization ) , defective liver function ( due to iron overload ) and defects in postabsorptive plasma homeostasis of fatty acids have been put forward to explain the pathogenesis of this sca - associated lipid abnormalities.913 however , it is worthy of note that this lipid phenotype is generally recognized as a risk factor for cardiovascular diseases .\nzorca et al.11 reported that elevated plasma tg is a potential risk factor for pulmonary hypertension ( ph ) in sca subjects . the impact of disordered lipid metabolism on the course of sca and its numerous complications are not yet clearly defined . also , there is little information on the lipid profile of sca subjects in voc . due to the present dearth of knowledge\n; this study determined the lipid profile of adult nigerians with sca in vaso - occlusive crisis ( voc ) and in steady state ( ssca ) .\neighty - two participants comprising 58 adults with sca ( 30 in steady state and 28 in voc ) and 24 age - matched healthy individuals with hbaa genotype were recruited into this study .\nthe sca ( hbss ) subjects were recruited from the hematology day care unit , department of hematology , university college hospital , ibadan after approval by university college hospital ( ui / uch ) joint ethics review committee , and informed consent by participant .\nsteady state ( ssca ) and vaso - ooclusive crisis ( voc ) were defined as earlier reported.14 subjects with other forms of genotype apart from hbss and hbaa , diabetes mellitus , hypertension , human immunodeficiency virus ( hiv ) , hepatitis , cancer and with established endocrine dysfunctions were excluded from the study .\nblood pressure ( bp ) was obtained using a mercury sphygmomanometer after at least 10 minutes of rest .\nafter an overnight fast of about 10 hr , 5 ml of venous blood was obtained from each sca subject in steady state ( ssca ) and the controls .\nsamples were collected upon admission in the voc group as voc is an acute clinical condition hence ; could not have been predicted for possible overnight fast .\nmost subjects in voc would probably be anorexic because of the acute pain they were going through .\nblood samples were dispensed into edta - containing samples bottles and after determining the packed cell volume ( pcv ) and total white blood cell count ( wbc ) , plasma was appropriately obtained and stored at 20c until analyses were done .\nhaemoglobin phenotype of each subject was determined using standard electrophoretic method at ph 6.8 while pcv and wbc were determined as described by cheesbrough.15 plasma lipid profile was determined using enzymatic method while ldl was calculated using friedwald equation.16 the distribution of the data was assessed using histogram with normal curve .\nresults are presented as mean standard deviation or as median ( interquartile range ) for gaussian and non - gaussian distributed data , respectively .\nanalysis of variance ( anova ) or kruskal - wallis test was used to compare all the three groups while differences between two groups were determined using independent student 's t - test or man - whitney u as appropriate .\nresults are presented as mean standard deviation or as median ( interquartile range ) for gaussian and non - gaussian distributed data , respectively .\nanalysis of variance ( anova ) or kruskal - wallis test was used to compare all the three groups while differences between two groups were determined using independent student 's t - test or man - whitney u as appropriate .\npcv , tc , hdl and ldl were significantly lower while wbc was significantly higher in sca compared with the control subjects .\nthere was slight , but insignificant elevation of tg in sca compared with the control subjects . in table 2 , all the components of the lipid profile between the three groups ( ssca , voc and controls ) were significantly different .\nother components of the lipid profile had no specific pattern of differences . characteristics of the subjects in table 3 , tc and hdl were significantly lower while tg / hdl was significantly higher in sca subjects in steady state ( ssca ) compared with the control subjects .\nsimilarly , tc and ldl were significantly lower in sca subjects in vaso - occlusive crisis ( voc ) compared with controls . however , tc , tg , ldl and tg / hdl were significantly lower while hdl was significantly higher in voc compared with ssca .\ncomparison of lipid profile in ssca , voc and control subjects using anova to find out if there is any interaction between wbc and lipid profile , sca subjects were classified into two groups based on the mean wbc value ; 11.97 ( 10/l ) [ table 1 ] into 11.97 ( 10/l ) and > 11.97 ( 10/l ) groups .\nas shown in table 4 , the two groups had similar lipid profile but they exhibited a similar pattern to that observed when ssca were compared with voc .\nthere was insignificant reduction in the levels of tc , tg , ldl , tg / hdl and insignificant elevation of hdl level in sca subjects with > 11.97 ( 10/l ) wbc compared with sca subjects with 11.97 ( 10/l ) lipid profile in ssca , voc and control subjects pattern of lipid profile based on mean total white blood cell count ( wbc ) in sca subjects\ndespite intense research for over 4 decades , mechanism of lipid homeostasis alteration in sca subjects is not yet fully understood.11 the observed lower levels of tc , hdl and ldl in the combined sca subjects ( ssca and voc ) are not novel findings .\nhypocholesterolemia has been widely reported in sca subjects1112 and was thought to be due to increased cholesterol utilization consequent to increased erythropoiesis of sca .\nhowever , the reports of westerman17 and ngogang et al.,18 showed that hypocholesterolaemia is a common feature of both haemolytic and non - haemolytic anaemia and that serum cholesterol is in equilibrium with the cholesterol content of total red cell mass .\nit was , therefore , suggested that sca - associated hypocholesterolemia is a consequence of anaemia itself and not increased erythropoiesis.1117 the interaction between sca complications such as voc and disturbed metabolic homeostasis in individuals with sca has been reported.1419 in this study , tc and ldl decreased progressively from control - to - ssca - to - voc .\nssca had lower tc and hdl while voc had lower tc and ldl compared with the control subjects .\nthis observation further confirms that sca - associated hypocholesterolemia might be anaemia dependent as intense haemolysis has been associated with various complications of sca.20 also , tg / hdl was higher in ssca than the control groups .\nthe ratio of tg to hdl has been reported to be relevant in determining the risk of clinical vascular disease .\nit has been used to identify diabetic patients with an atherogenic lipid profile and has been found suitable in selecting patients needing earlier and aggressive treatment of lipid abnormalities.21 our observation is not surprising as the ssca group had slightly higher tg with concurrent lower hdl compared with the control subjects .\nzorca et al.11 reported that high tg / hdl is associated with endothelial dysfunction and suggested that high tg / hdl is a potential risk factor for pulmonary hypertension .\nalthough ldl is usually low in sca subjects , belcher et al.22 showed that ldl from sca subjects is more susceptible to oxidation and cytotoxicity to endothelium .\nour observation , together with earlier reports , indicates that anaemia - associated lipid homeostasis disturbance could predispose sca subjects to various vascular diseases .\nunfavorable plasma fatty acid composition has been associated with clinical severity of sca.23 similarly , nouraie et al.20 reported that intensity of haemolytic anaemia is an independent risk factor for the development of sca complications such as ph and hypoxaemia . in this study ,\nplasma levels of tc , ldl and tg / hdl were lower in voc compared with ssca .\nthis observation could be as a result of possible intense haemolytic anaemia in voc which would facilitate the attainment of a new equilibrium between the serum cholesterol and cholesterol content of total red cell mass.1117 the observed higher hdl in voc compared with ssca supports the report of darbari et al.3 which showed that higher hdl is independently associated with frequent voc .\nthe observed elevated plasma hdl could be a marker of less marrow activity in sca subjects since formation of erythroid cell membrane requires cholesterol.1124 the reason for the observed lower tg in voc compared with ssca is presently unclear\n. however , intake of drugs and/or reduced food intake ( due to possible anorexia ) before presentation may be responsible for this observation .\nfurther research work is still required to properly understand the disturbance in lipid homeostasis following voc as standard fasting period could not be ensured in our voc subjects .\nalso , the small sample size used in this study could limit proper data interpretation .\nour study further confirms the widely reported defective lipid homeostasis in adults with sickle cell anaemia .\nit also showed that the alteration in the lipid metabolism becomes pronounced with vaso - occlusive crisis .", "answer": "background : abnormal lipid homeostasis has been reported in sickle cell anaemia ( sca ) as well as in other haematological disorders \n . however , there is little information on the lipid profile of sca subjects in vaso - occlusive crisis ( voc ) . \n this study determined the lipid profile of adult sca subjects in voc and in steady state ( ssca).materials and methods : fifty - eight ( 58 ) adults with hbss ( 30 in steady state and 28 in vaso - occlusive crisis ) and 24 age - matched healthy individuals with hbaa genotype were recruited into this study . \n standard methods were used for the determination of blood pressure ( bp ) , packed cell volume ( pcv ) , total white blood cell count ( wbc ) and haemoglobin phenotype . \n after an overnight fast , 5 ml of venous blood was obtained from each ssca and the controls while samples were collected upon admission in the voc group . \n plasma lipid profile was determined using enzymatic method . \n differences between two groups were determined using independent student 's t - test or man - whitney u as appropriate . \n p - values less than 0.05 were considered significant.results:plasma total cholesterol ( tc ) and high density lipoprotein ( hdl ) were significantly lower while the ratio of triglyceride ( tg ) to hdl ( tg / hdl ) was significantly higher in ssca compared with the controls . \n low density lipoprotein ( ldl ) and tc were significantly lower in sca subjects in voc compared with controls . \n however , tc , tg , ldl and tg / hdl were significantly lower while hdl was significantly higher in voc compared with ssca.conclusion:sickle cell anaemia subjects have defective fasting lipid metabolism which becomes pronounced with voc .", "id": 646} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nangiomyxomas are benign , locally infiltrative mesenchymal neoplasms with a predilection for the female pelvis and perineum in their reproductive age group .\nthese tumours often reach too large dimensions before becoming clinically symptomatic and they usually tend to recur after excision . accurate preoperative diagnosis should alert the surgeon to the need for wide excision , which is essential for prevention of local recurrence .\nthis is easily done with robotic assistance due to its advantages like three dimentional vision and advanced degree of freedom within the pelvic cavity .\nwe report here a similar case presenting as a retrovesical tumor in a male patient , which was excised with robotic assistance .\na 62-years - old male presented to us with mild obstructive lower urinary tract symptoms ( luts ) since last 1 year , with a history of acute retention of urine 3 month back with failed catheter free trial .\nhe underwent holmium laser enucleation of prostate ( holep ) elsewhere with histopathology reporting as benign prostatic hyperplasia .\npatient failed to void after catheter removal and on further evaluation he was found to have pelvic mass .\ndigital rectal examination revealed a cystic mass simulating benign prostatic hyperplasia ( grade 3 ) .\nmagnetic resonance imaging ( mri ) pelvis revealed a well - marginated lesion within the prostate gland resulting into significant prostatomegaly with no extra prostatic extension [ figure 1 ] .\ntransrectal biopsy was done , which was inconclusive with no identifiable prostatic tissue . in view of discrepancy between mri report and biopsy report we performed cystoscopy which showed a hump in the prostatic urethra extending into the trigone , with prostatic lobes not visible ( because of previous holep ) .\ntumor was ~6 cm 4 cm 2.5 cm in size [ figure 2 ] .\nwe were not able to separate the mass from bladder due to difficulty in entering into proper plane .\nhence we opened bladder deliberately and resected from within the bladder , closed cystostomy and drained bladder .\nhisto - pathological examination [ figure 3 ] revealed moderately cellular tumor composed of sheets of spindle to stellate shaped cells with vascular channels in between . on immunohistochemistry cells were positive for desmin , focal positivity with smooth muscle antibody ( sma ) , s100 and ki-67 .\nmagnetic resonance imaging showing a well - marginated lesion within the prostate gland resulting into significant prostatomegaly , with no extra prostatic extension .\nalso gross specimen of the tumor with gelatinous appearance and size of ~6 cm 4 cm 2.5 cm .\nhistopathology revealed moderately cellular tumor composed of sheets of spindle to stellate shaped cells with vascular channels in between . on immunohistochemistry cells were positive for desmin , focal positivity with smooth muscle antibody , s100 and ki-67 .\naggressive angiomyxoma was first described in 1983 by steeper and rosai , and fewer than 150 cases have been reported in the world medical literature .\nthe recurrence rate is high , and often extensive resections are performed with considerable morbidity . in men ,\nthe tumour involves analogous sites including the scrotum and inguinal area and usually appears at an older age .\nthere might be a relation with hormonal status that might explain a female to male ratio of slightly more than 6:1 .\nthese lesions are characterized as soft , non - encapsulated tumours with finger - like projections infiltrating the surrounding soft - tissues .\nthe tumour grows slowly and is benign as suggested by the histology and by the fact that it shows no tendency to metastasize .\nthe low attenuation at unenhanced computed tomography ( ct ) and high signal intensity at t2-weighted mri are consistent with a myxoid matrix , high water content within the mass , or both .\nthe enhancement of t1-weighted mri after administration of gadolinium is related to the vascularity of aggressive angiomyxoma .\nthere is no evidence of gross fat within the mass , which distinguishes this tumor from other fat - containing tumors that also occur in the pelvis of women .\nsurgery is usually the first line of treatment ( open , laparoscopic or robotic assisted ) , radical surgery with wide margins and long - term follow - up is advised .\nhormonal suppression seems to be a plausible treatment option because these tumours occur predominantly in premenopausal women of reproductive age , may grow rapidly during pregnancy and have been shown to express immunohistochemical positivity for oestrogen and progesterone receptors .\ntheir surgery is challenging because of the infiltration and the difficult dissection . in the past , most authors advocated wide excision along with genito - urinary and digestive tract resections if necessary .\nmost recently robotic assisted laparoscopic excision has been promising , as seen in our case .\nmale angiomyxoma , athough a rare benign tumour , should be considered in the diferential diagnosis of pelvic mass in a male patient presenting with severe obstructive luts , and robotic assisted excision should be utilised wherever available .", "answer": "angiomyxoma is a rare tumour found predominantly in pelvis of young females . \n less than 150 cases have been reported , more than 90% in females and only few cases in males . \n its surgical excision is a big challenge and usually leads to recurrence due to incomplete excision . \n we report a case of retrovesical angiomyxoma in an elderly male . \n the aim of this report is to highlight the rarity of this disease , especially in males , and robotic assisted excision as an evolving option of treatment .", "id": 647} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncurrently , nanoparticles ( nps ) are used in several scientific applications , but among these silver nanoparticles ( ag - nps ) are predominant .\nthis is because of several characteristic features of this type of metal np.13 antimicrobials and nanocomposite fabrication are some of the highly useful applications , among others , of applications that were attributed to ag - np.4,5 in the fabrication of nps , it is very important to control particle size , shape , and morphology .\nlaser ablation in liquid media is a simple and clean method for synthesis of nps.69 in this technique , there is no need to use any chemical reagents ( such as nabh4 ) in the fabrication process or any purification techniques to characterize the produced nps .\nfor example , nps using fatty acids ( oleic and lauric acid ) and vegetable oils as stabilizers have been synthesized.1012 it was found that these materials consist of amphiphilic molecules with polar carboxylic groups which are able to adsorb nps , and their nonpolar long carbon chain prevents nps agglomeration through steric repulsion . castor oil is a vegetable oil obtained by cold pressing the seeds and subsequent clarification of the oil by heat .\nit has high viscosity , high polarity , and very low vapor pressure and optical activity in comparison with other oils .\ncastor oil is classified as a safe and effective stimulant laxative by the us food and drug administration ( fda ) .\nit is a triglyceride containing fatty acid chains , 90% of which are ricinoleic acid .\noleic and linoleic acids are the other significant components.12 with the above characteristics , it is expected that castor oil can be used as a good stabilizer in nps fabrication . in this study\n, we report fabrication of ag - nps in castor oil . to the best of our knowledge ,\nfabrication of ag - nps in castor oil using laser ablation has not been reported previously .\nfor the fabrication of ag - nps , a silver plate was ablated by laser in castor oil for 10 min .\nas shown schematically in figure 1 , the plate with high purity ( > 99.99% ) was located 5 mm behind a glass cell wall filled with 10 ml of castor oil .\na nanosecond - pulsed q - switched nd : yag laser ( brilliant ; lambda photometrics ltd , hertfordshire , uk ) with 10-hz repetition rate , 5-ns pulse duration , and 360 mj / pulse energy at its original wavelength ( 1064 nm ) was applied .\na lens with focal length of 250 mm was used to focus the laser pulses onto the silver plate . during plate ablation ,\nan atomic absorption spectrometer ( aas - s series ; thermo scientific , san jose , ca ) was used to measure concentration of ag - nps in castor oil .\nthe obtained concentration of ag - nps in castor oil was 0.13 mg / l . due to the high viscosity of castor oil\nthe prepared sample was characterized using a uv - vis double beam photospectrometer ( shimadzu , columbia , sc ) , a transmission electron microscope ( tem , hitachi h-7100 ; hitachi , tokyo , japan ) , and a fourier transform - infrared ( ft - ir ) spectrometer ( 1650 ; perkin elmer , waltham , ma ) .\nfigure 2a indicates the absorption spectrum of the castor oil immediately after laser ablation of the silver plate inside it .\nthe appearance of the maximum absorption peak around 400 nm confirms that the solution contained ag - nps , and that this peak originated from the oscillation of collection of free conduction electrons of ag - nps , which is called surface plasmon resonance .\nthe ultraviolet - visible spectrum of the ag - nps in castor oil was measured after a period of 2 months in order to check the ability of castor oil as a stabilizer . as shown in figure 2b\n, the spectrum does not show any significant change in comparison with the spectrum of the freshly prepared sample ; however , there is a small reduction in absorption .\nthis showed that the ag - nps produced in castor oil using the laser ablation technique were stable and did not agglomerate during storage of the sample at room temperature for quite a long period of time .\nthe slight decrease in absorption intensity was possibly due to the sedimentation of larger particles .\nthe spherical shape nps can be very appropriately used for drug loading and for most biological applications such as antibacterial properties.13 figure 3 shows an approximate 5.06 nm average diameter for freshly prepared ag - nps obtained from two areas .\nnps are formed via nucleation , transition , and crystal growth of materials such as silver atoms , clusters , and droplets that were emitted from the silver plate upon laser ablation.14 castor oil can adsorb the produced ag - nps and long - chain hydrophobic moieties protect them through a steric stabilization mechanism .\nft - ir spectroscopy of castor oil and castor oil containing ag - nps ( figure 5 ) shows absorption bands at 3448 , 2923 , 2857 , 1739 , and 1160 cm related to the vibrational - stretching mode of o h ( intermolecular hydrogen bond ) , c h ( sp ) , c h ( sp ) , co , and c o , respectively .\nin addition , the appearance of the absorption band at 3780 cm can be attributed to nonhydrogen - bonded o \nwe believe that the existence of ag - nps prevents intermolecular hydrogen bonding , and therefore , the vibrational stretching modes of free o h appear at a higher wave number.15\nag - nps have been successfully prepared in castor oil by laser ablation from a silver plate . the results obtained showed that the produced ag - nps were well dispersed and also stable for quite a long period of time .\nthis ability of castor oil to prevent agglomeration of ag - nps is due to the presence of long - chain hydrophobic moieties .", "answer": "silver nanoparticles were fabricated by ablation of a pure silver plate immersed in castor oil . \n a nd : yag - pulsed q - switch laser with 1064-nm wavelength and 10-hz frequency was used to ablate the plate for 10 minutes . \n the sample was characterized by ultraviolet - visible , atomic absorption , fourier transform - infrared spectroscopies , and transmission electron microscopy . \n the results of the fabricated sample showed that the nanoparticles in castor oil were about 5-nm in diameter , well dispersed , and showed stability for a long period of time .", "id": 648} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncutaneous hyperpigmentation is a recognized adverse effect of chronic minocycline use occurring in up to 50% of patients , . in a recent study performed at the mayo clinic , 54% of 291 patients receiving long - term minocycline suppression for orthopedic infections developed some degree of hyperpigmentation after a mean follow - up of 4.8 years . in this cohort ,\nfactors associated with minocycline - induced cutaneous hyperpigmentation ( mich ) include a history of vitamin d deficiency , presence of a shoulder prosthesis , noncirrhotic liver pathology , and use of a concurrent medication ( e.g. , calcium channel blocker ) also known to cause hyperpigmentation .\nmich is not associated with adverse clinical effects , and it is mostly cosmetic in nature .\nwe herein present a rare case of extensive skin hyperpigmentation involving both lower extremities in a patient receiving long term minocycline .\nin june 2016 , a 76-year - old male with a past medical history significant for nephrolithiasis and diverticulitis , presented to the authors institution with extensive hyperpigmentation involving both lower extremities .\nhe underwent a left total knee arthroplasty in 1988 at an outside institution and underwent revision surgery in 1992 . in 2001\n, he underwent a second revision for fractured patella that was complicated by an infection with a coagulase - negative staphylococcus .\nhe received six weeks of treatment with parenteral vancomycin followed by oral trimethoprim - sulfamethoxazole .\noperative cultures from the knee grew enterococcus sp . , prevotella sp , viridans group streptococcus , as well as candida parapsilosis . after completing antimicrobial treatment with vancomycin , ertapenem and fluconazole\n, he underwent reimplantation using a rotating hinged knee arthroplasty in september 2005 ( fig .\nsince that time , the patient was maintained on oral minocycline chronic suppression . in 2010\nhe uses a brace as well as a cane to ambulate . at a follow - up in february 2012\nwhen he was seen again in june 2016 , there was extensive blue - gray pigmentation in both cheeks and in the lower extremities ( fig .\n2 ) , as well as sub - ungual blue - gray pigmentation in both hands ( fig .\nthere are three types of pigmentation patterns that can result from taking minocycline for long periods of time .\ntype i is a blue - gray pigmentation occurring around areas that were previously inflamed .\ntype ii has the same appearance as type i and covers areas of normal skin such as the anterior shins , arms , and ankles .\ntype iii is a muddy brown pigmentation usually occurring on areas of the skin that are exposed to the sun .\nthe blue - gray pigmentation is due to the deposition of iron within the dermal macrophages .\nthe diffuse hyperpigmentation seen in the patient presented in this case report includes both types i and ii . blue - gray pigmentation is clearly seen around the scar on the left knee from his knee replacement surgery ( type i ) .\nhyperpigmentation is also distinctly seen on the shins of both legs and around the ankles of the patient ( type ii ) .\nhyperpigmentation is predominantly seen with minocycline and less likely to occur with other tetracyclines such as doxycycline .\nminocycline is five times more lipophilic than doxycycline ; hence , central nervous system adverse events are more common with minocycline .\nalthough doxycycline may have a higher incidence of gastrointestinal upset and photosensitivity , minocycline has an increased likelihood of severe and permanent cosmetic adverse events and central nervous system adverse events . in the study of orthopedic patients on long - term minocycline suppression ,\nthese side effects are an addition to gastrointestinal adverse effects that can also occur with minocycline . in the absence of data to show that minocycline is superior to doxycycline for long - term suppression of infections including orthopedic infections , the authors propose that doxycycline be looked upon favorably when chronic use is indicated .", "answer": "cutaneous hyperpigmentation is a recognized adverse effect of chronic minocycline use occurring in up to 50% of patients . in this report \n we present a rare case of extensive skin hyperpigmentation involving both lower extremities in a patient receiving long term minocycline . \n the patient was receiving minocycline as suppression for chronic prosthetic joint infection . \n risk factors associated with minocycline - induced cutaneous pigmentation ( mich ) will be reviewed .", "id": 649} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n, individuals can live for 80100 years , much longer than in past generations . according to the who , the proportion of people over 60 years of age is increasing quickly and is expected to exceed 2 billion people worldwide by the year 2050 .\nimmune senescence comprises a set of changes occurring to the innate and adaptive immune responses that accompany human aging .\nage - associated immune senescence is a catch - all phrase that has been used to describe a plethora of changes to the immune system over the lifespan .\nimmune aging is a complex process that comprises many reconstructions and regular changes rather than being a simple one - way reduction in all immune functions ; thus , all parts of the immune system in immune senescence are not affected equally .\nfor instance , it has been observed that natural immunologic structures that are common to all living things are less affected than are acquired immune system structures .\nactive participation of inflammation , which forms the most basic defense mechanism in the aging process , is also an indicator of this .\nthe decline in immune function with age is unanimously recognized and supported by epidemiologic and clinical studies [ 46 ] .\nmany studies have demonstrated that immune functions and cells in the immune system are affected by aging .\nsome studies reported that differences in immune system due to aging vary between males and females .\nsex - related differences in immune system susceptibility have also been observed in several mouse models and may be related to differences in the expression patterns of immune response genes .\nunderstanding the basis of sex and age differences in immune response genes is important for developing new approaches to prevention , diagnosis , and treatment of diseases .\nour aim in this study was to investigate how lymphocyte subgroups in peripheral blood are affected by aging among males and females .\nstudy participants were 70 healthy individuals from 3 different age groups , observed from january 2010 to january 2012 .\nparticipants were divided into 3 different groups according age : group 1 ( n=20 ) was 2545 years old ( 10 males , 10 females ) , group 2 ( n=25 ) was 4565 years old ( 12 males , 13 females ) , and group 3 ( n=25 ) was older than 65 years old ( 13 males , 12 females ) .\nwe determined the average levels of cd3 + , cd4 + , cd8 + , cd19 + , cd16+/cd56 + , cd3+/cd69 + , and cd19+/cd69 + by age group and sex .\nindividuals who were smokers or who had a chronic disease were excluded from the study .\ncollected data were statistically analyzed by kruskal - wallis - anova , with p<0.05 considered to be statistically significant .\nwe found a significant reduction in the rate of cd3+t cells related with age , but no significant change in cd19 + b cell rates ( p<0.005 ) .\nanother noteworthy result was that the level of cd8+t cells was lower in males compared to females and varied by age group ( p<0.005 ) .\nlevel of activated t and b cells did not differ by age group , but levels of activated b cells ( cd19+/cd69 + ) decreased with age in males ( p<0.005 ) ( figure 1 ) .\nprojections indicate that by 2025 the world population over age 65 will be increasing 3.5 times as rapidly as the total population and the proportion of individuals age 60 years and older , which accounted for 10% of the world population in 2000 , will increase to approximately 22% of the world population by 2050 .\naging is a highly complex and continuous process that affects almost all organ systems , causing molecular and physiological changes , both qualitatively and quantitatively .\nthe aging of the immune system is a dynamic process that may at least partly reflect adaptation of the response to the evolving pathogen surroundings [ 16 ] .\naging is increasingly recognized as being associated with a pro - inflammatory state that plays an important role in the development of chronic diseases .\nimmune senescence comprises a set of changes occurring to the innate and adaptive immune responses that accompany human aging . these result in complex manifestations of still poorly defined deficiencies in the elderly population . in the evaluation of t and b cell activations ,\nno change due to aging was observed in level of activated t cells . on the other hand ,\nour results show that levels of activated t and b cells did not differ by age group .\nwe found that that aging reduces activated b cell ( cd19+/cd69 + ) levels of males .\nmales have shorter life expectancy than females due to the effects of aging making them more sensitive . the immune system in males\n, we observed the lower cd8+t cell rates of males compared to those of females , especially when compared by age .\ntherefore , we especially wanted to observe the changes in peripheral blood lymphocytes of males and females who belong to different age groups .\nrecent studies have revealed that changes in the number of lymphocytes and a decrease in cell activation and proliferation appear with aging . however , the difference between males and females in immune senescence is still a hotly debated topic because many different factors may be involved .\ndifferences between males and females in susceptibility to infection and differences in prevalence of autoimmune diseases by sex may help understand these differences in aging and health [ 25,12 ] .\nin general , it has been demonstrated in human and mouse studies that females produce stronger humoral and cellular immune responses against varied antigens than males do .\nthis difference also plays a role in female allograph rejection , which has been demonstrated in mouse studies .\nfor instance , it is reported that female estrogen stimulation , which leads telomerase induction by c - myc , has an anti - aging effect .\nanother theory that has been put forward about this topic in recent years suggests that depending on the development needs mitochondria in female cells have a better adaptation than male cells have [ 1113 ] .\nthe immune response to infections , immunizations , and tumors in the elderly is quite different from that in young people .\nour study shows that there may be differences between males and females in terms of immune senescence .", "answer": "backgroundage - associated immune senescence is a catch - all phrase that has been used to describe a plethora of changes to the immune system across the lifespan . \n aging is associated with a decline in immune function . \n our aim in this study was to investigate how lymphocyte subgroups in peripheral blood are affected by aging among males and females.material/methodsstudy participants were 70 healthy individuals from 3 different age groups , observed from january 2010 to january 2012 . \n the average levels of cd3 + , cd4 + , cd8 + , cd19 + , cd16+/cd56 + , cd3+/cd69 + , and cd19+/cd69 + were determined for each group and compared in terms of age and sex.resultswe found significant reduction in the level of cd3+t cells related with age , but no significant changes in cd19 + b cell levels ( p<0.005 ) . \n aging significantly reduces activated b cell ( cd19+/cd69 + ) levels in males ( p<0.005).conclusionsour results show that there may be differences between males and females in terms of immune senescence .", "id": 650} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndespite of presentation of medical ethics as a new science in academic teaching , the ethical concepts have been alongside the medicine , and its antiquity back to the medicine history .\nfor instance , literatures such as hippocratic oath letter , liturgy of ibn maymun , and shirazi ethics ordinance are the old literatures in which the principles such as the necessity of patient preference defender on the physician and observing the principle of confidentiality have been emphasized . however , in the past literature using physician s commitment and pledge \nhuman being is a creature with physical , mental and spiritual dimensions which has rights during the health and illness .\npatient rights are the very expectations he has from the health care services and must encompass his physical , mental , spiritual and social needs which are manifested as criteria , standards , rules and laws ( 4 , 5 ) .\nemphasis on patient rights in the health care services particularly maintains patient dignity as a rank of a human , and is considered important especially when patient s vulnerability easily expose him to the violations and weaknesses of the health care system ( 6 ) .\nconsidering that health is the most important existence aspect of every person and according to the article 29 of the constitution , providing health is the most important commitment of the government of islamic republic of iran ; because of this , in 2002 , for the first time the patients right charter was developed in iran and was notified by department of health , treatment and medical education ( 7 )\n. the patients right charter of iran was approved by health policy council with a new and comprehensive viewpoint aimed to clarify the rights of the health services recipients and observance of moral standards in the treatment and medical fields in november 26th , and in december 1st it was communicated to the relevant centers ( 1 , 8 , 9 ) . in this charter patient satisfaction is considered as one of the characteristics of hospital effectiveness ( 9 ) .\ntoday , the issues related to the quality of health care services , attention to the patients as customers and accomplishing their satisfaction are the main priorities and are of high importance .\none of the important factors in patient satisfaction is regarding their demands and observing their rights and providing care along with respect ( 6 ) .\nawareness of the patients rights and observing them accomplishes more satisfaction of the patient , physician and other medical team and hospital staff and will lead to the spread of good morals among patients and medical team ; so eventually the moral status of all the individuals such as patients and medical team will be upgraded , but otherwise provided not observing these rights , it would lead to distrust to health care team . if there is no trust between medical staff and patients , it would lead to damages and losses for the patient and the medical team .\nfurthermore , it would lead to terrible and unpleasant occurrences which are difficult to compensate and would be followed by the legal prosecution ( 5 , 10 ) . protecting the patient rights by the nurses\nonly will be possible when they have gained necessary knowledge about it and suitable conditions be provided for respecting these rights ( 11 ) .\nappropriate care and observing patient rights require nurses knowledge which would be possible through different ways such as side studies , retraining courses , and academic courses during education ( 5 ) . in the studied\nresearches about the nurses level of knowledge from patient rights , several aspects were mentioned .\nnasiriani et al ( 5 ) and houshmand et al ( 11 ) reported good nurses level of knowledge in yazd hospitals and teaching public wards of tehran hospitals respectively .\nobserved moderate and parsinia et al obtained weak nurses knowledge in tehran and karaj hospitals respectively ( 10 ) .\nthe clinical researchers in different wards of teaching hospitals have reported that the patients rights have been ignored or have not been considered seriously due to shortage of nursing staff , high number of patients in the hospitals , psychological pressures and etc .\ntaken together , we decided to evaluate the nurses knowledge about patients rights in one of the teaching hospitals of tehran city .\nthis was a descriptive cross - sectional study in which the nurses knowledge about patient rights was determined .\nthe study samples consisted of 156 nurses who have been selected randomly from one of the teaching hospitals of tehran .\nthe data collection instrument was a two - part questionnaire ; the first part included the demographic information ( age , gender , marital status , work experience , educational level , etc . ) ; the second part consisted of 10 questions according to the 10 section of patients rights charter of iran ( 11 ) .\nthis part determined the following areas about patient rights : right to receive essential information about health care providers , rate of tariff , target insurance coverage if sent to the other medical centers .\nright to receive respectful and quick treatment and care regardless of cultural and racial factors .\nright to know about the probable complications , treatment options and participate in the ultimate treatment choosing .\nright to make a decision about the presence of those who are not directly involved in the treatment process .\nright to announce personal satisfaction from ending the treatment and referring to other centers , and right to preserve privacy and being ensured about confidentiality of all of the medical information .\nthe answers of the study subjects to the questions were quantified by measuring a three - score scale ; good ( 3 scores ) , moderate ( 2 scores ) and weak ( 1 scores ) .\nthe maximum score in the questionnaire was 30 scores which were considered 2130 as high knowledge , 1020 as moderate knowledge and less than 10 as weak knowledge .\nthe validity was done using content validity i.e. the questionnaire was given to 10 faculty members of universities of tehran and after collecting the comments , the relevant comments were applied .\nthe validated questionnaire was given to 10 eligible study subjects for reliability and in both stages the questionnaire was completed with a 10-day interval and the required correlation of the first and second answers and confidence was obtained r = 0.90 and finally these people were excluded from the study population .\nthe questionnaires were completed during two weeks by direct referring of the researcher to the wards . in order to observe ethics , confidentiality and integrity ,\nthe mentioned questionnaires were anonymous and in all stages of the study the information were collected confidential and were kept by the researcher .\nthe review of the demographic variables indicated that the majority of the nurses were females ( 76.28% ) with mean age of 34.31 7.3 .\nmost of them ( 91.2% ) had bachelor degree and were married ( 62.82% ) . in terms of employment and work experience , almost half of nurses ( 47.43% ) were contractual , 46.79% had 610 years of work experiences , 30.99% never passed any course about patient rights and 30.99% of them had the simultaneous experience in public and private sectors .\nno association between the variables of gender , age , degree and marital status and nurses knowledge about patient rights was found .\nthere was no significant difference between them in terms of work section , work experience and simultaneous work in the public and private sectors , however there was a significant difference between their level of knowledge about patient rights and simultaneous work in the public and private hospitals and work experience ( table 1 ) .\nthe findings of the study about the nurses level of knowledge in different areas indicated that the highest level of knowledge ( 95.51% ) was in the area of right to preserve privacy and being ensured about confidentiality of all medical information and the lowest level was right to receive essential information about health care providers , rate of tariff , target insurance coverage if sent to the other medical centers .\nobserving patients rights is the most important ethical issue in a hospital which should absolutely be considered . regarding patients rights and respecting them are two main factors for patients care .\nobserving patients rights means the accountability of all health care staff to the patients at the time of treatment and care giving ( 12,13 ) .\npromoting patients rights is a multidimensional issue and in order to achieve it , comprehensive efforts should be done .\nworld health organization has offered some strategies such as active participation of health care recipients and providers policy making and extending educational programs for health care providers and entire community ( 11 ) .\nthe findings of the study showed that nurses level of knowledge about patients rights in terms of the variables such as type of the hospital , work experience , degree , age and gender was good , moderate and weak in 58.33% , 39.10% , and 2.56% of them respectively . in the studies conducted in karaj hospitals ( 10 ) and the public wards of teaching hospitals of tehran ( 11 ) also the nurses level of knowledge reported as weak .\ntoday patients are more aware of their rights and physicians responsibilities and commitments and also hospitals managements regarding their rights ( 14 ) and they are more insisting on their principle rights ( 2 ) . therefore it is highly needed that nurses with low level of knowledge , and the other health care providers be aware of patients right charter and increase their knowledge .\ndetermined the reasons of the nurses low level of knowledge as lack of institutionalization and regulation of the rights ( 12 ) ; lack of adequate time for studying and researching due to various obstacles such as poor economic conditions ; lack of positive vision in selecting nursing profession ; tough job conditions in the hospitals such as large number of the patients versus staff shortages , and lack of necessary facilities such as adequate and suitable libraries ( 5 ) .\nthe results indicated that there was a significant and direct association between level of knowledge and simultaneous jobs in the public and private hospitals ( p=0.01 ) i.e. the nurses who provided services simultaneously in the public and private hospitals had higher level of knowledge .\nthe reason might be due to regulations and rules which are performed more in the private hospitals compared to the public hospitals i.e. no implementation of patients right charter which may be followed by punishment .\nthe findings of the present study indicated that in the area of right to preserve privacy and being ensured about confidentiality of all the medical information , the nurses had the highest level of knowledge . in the patients\nright charter codified in 2009 it says observance of the principle of confidentiality is necessary about all the information related to the patient except for the cases the law excluded ( 1 ) . in a comparative study about the patients right charter in the selected countries with iran in 2007 , it was indicated that regulations of iran for the right of the confidentiality of the patient information and medical records is similar to the other countries such as hungary , hong kong , new zealand , united states , south africa , european union and lithuania ( 14 ) . unlike the above results , in canada\nit was indicated that 84% of the medical staff did not have enough knowledge about commitments and obligations of the law about confidentiality of the information and privacy of the patients information ( 15 ) .\nour findings indicated that there was a direct and significant association between level of knowledge and work experience ( p= 0.008 ) and the level of knowledge of the study subjects from patients rights charter was increased by increasing work experience which was in accordance with the studies of nasiriani et al . and\nin addition , the study indicated that there was no association between level of knowledge and degree and increasing degree had no effect on the level of knowledge . in a study in karaj\nit was mentioned that the level of knowledge of the technicians was higher in comparison with supervisors and matrons and the most important reasons were sense of job security , professional status and disregardness of matrons and supervisors to the important tasks ( 10 ) .\nthe findings indicated that nurses in the area of right to receive essential information about health care providers , rate of tariff , target insurance coverage if sent to the other medical centers had the lowest level of knowledge .\nthe patients right charter codified in 2009 states that information must be given to the patient at the right time and appropriate condition by considering individual characteristics such as language , degree and perception ; however the patient has the right to access all the information recorded in his / her clinical records ( 16 , 17 ) . in the patients right charter of some countries such as canada and united states unlike the other countries such as iran , hong kong , new zealand , africa , european union , lithuania ,\n right to ask for explanation about the costs has been discussed ( 14 ) .\nthe results indicated that 66% of the nurses was aware of the right to access to the health care providers during hospitalization , instead of 90% of turkish nurses ( 17 ) . nowadays ethical and legal concepts such as patient rights are included in the educational curriculum of greek and turkey ( 18 , 19 ) .\naccording to the considerable gap between development and realization of the patient rights ( 20 ) and the increased knowledge , claims and demands of the patients and also the results of this study , in order to observe patients right the following solutions are suggested : - encouraging the nurses to consider patients right charter seriously . - establishing and empowering the sanction of patients right charter - more emphasizing on concepts of professional ethics and patient rights in teaching nursing students - attending expertise meetings with presence of beneficiaries for evaluating barriers and presenting strategies in order to implement the patients right charter as soon as possible - providing periodic educational programs for health care providers and patients about patient rights\ngenerally , since 41.6% of the nurses of the study had not a proper level of knowledge about patient rights and considering the fact that awareness and knowledge can be the base of nurses performance and also patients increasingly are getting informed about their rights , the implementation of patients right charter is highly recommended .\nholding educational programs , seminars , workshops and academic panels for nurses , and nursing students help overcome difficulties .", "answer": "patients rights observance is one of the effective measures of patients satisfaction of health care services . \n we performed this study at the aim of evaluation of nurses awareness of patients rights in a teaching hospital in tehran.this cross - sectional study was conducted in 2010 . in this study 156 \n nurses were randomly selected . \n two - part questionnaire was used for data collection . \n the validity and reliability of questionnaire was determined and then it was distributed between subjects . \n the data were analyzed by spss version 15 using descriptive and inferential statistics . \n our results showed that % 58.33 , % 39.10 and % 2.56 of nurses have good , medium , and poor levels of awareness respectively . \n we observed a significant relationship between nurses awareness and work experience ( p=0.008 ) and concurrent work in public and private hospitals ( p=0.01 ) . \n the most of the nurses ( % 95.51 ) were aware of right to privacy protection and ensure confidentiality of information and the least of them ( % 33.97 ) were aware of right to receiving necessary information about the health care providers , the rate of tariff and insurance coverage.according to our survey it is concluded that implementation of patients right charter in this hospital is accompanied by some limitations which necessitates promotion of the nurses awareness about patients rights . \n taken together in order to enhance nurses awareness special measures and strategies should be considered .", "id": 651} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nclubbing of digits , periosteal new bone formation along the shafts of the tubular bones of the extremities and synovial effusions characterize hypertrophic osteoarthropathy ( hoa ) .\nprimary hoa is a rare syndrome , not associated with other systemic diseases , and usually occurs in childhood , whereas secondary hoa is associated with various underlying pulmonary and non - pulmonary causes , such as bronchogenic carcinoma and right - to - left cardiac shunts . although various intrathoracic malignancies have been associated with the development of hoa , it has been extremely rare for hoa to occur in a patient with a malignant neoplasm of the thymus .\nsince the first case was reported in 1939 , a few cases have been reported worldwide .\nrecently , we experienced a case of hoa with a thymic carcinoma , and herein report the case with a review of the literature .\na 63-year - old woman was referred to our hospital because she had a chief complaint of both leg pains .\nthe pain was noted several months ago without any prior history , such as trauma and it was wax and wane and slowly progressing .\nshe did not have any other systemic symptoms , such as weight loss or fever .\nher past and family history was not contributory except for the diagnosis of hypertension one year before and antihypertensive medication thereafter .\nphysical examination at presentation was normal except for tenderness of both the lower extremities and clubbing of the fingers ( figure 1 ) .\nlaboratory investigation showed no abnormal findings except for mild anemia ( hgb 10.2 g / dl ) .\nthe plain radiograph of both lower legs showed cortical thickening along the shaft of the tibia and the bone scan revealed diffusely increased uptake along the cortex of both lower extremities ( figure 2 ) .\nthe radiologic findings were not consistent with bone metastasis but with hypertrophic osteo arthropathy ( hoa ) . in order to find the possibility of the secondary hoa\n, we performed a chest radiograph , which revealed a left mediastinal bulging mass ( figure 3 ) .\nthe chest ct scan confirmed the presence of a soft tissue density mass in the anterior mediastinum with pericardial effusion ( figure 4 ) . for a pathologic confirmation\nmicroscopic examination showed irregular nests of poorly differentiated malignant cells with hyperchromatic and irregular nuclei ( figure 5 ) . according to the microscopic examination\nhypertrophic osteoarthropathy ( hoa ) begins as periostitis followed by new bone formation , which is seen as a solid lamination involving the proximal and distal diaphyses of the tibia , fibula , radius , ulna and , less frequently , the femur , humerus , metacarpals , metatarsals and phalanges .\nas the process of new bone formation progresses , these changes extend to involve metaphyses .\ninitial radiological finding is a radiolucent area between the new bone formation and subjacent cortex . in the long - standing process ,\npara - cortical increase of uptake is a characteristic finding of the bone scan study .\nproliferation of connective tissue occurs in the nail bed and volar pad of the digits , giving rise to clubbing .\nclubbing is almost always a feature of hoa but can occur as an isolated manifestation .\nthis isolated manifestation of clubbing may represent an early stage of hoa , so it may have the same clinical significance as hoa .\nsecondary hoa occurs in association with a variety of underlying disorders , including heart , lungs , pleura , gastrointestinal tract and liver .\nalthough several theories have been suggested for the pathogenesis of hoa , its underlying mechanism is still controversial .\n. then , most platelets are produced in the lungs , especially , in pulmonary capillaries , by physical fragmentation of cytoplasms of megakaryocytes , because they are large and can not pass unchanged through the normal lung vasculature , which is narrow . in patients with disorders associated with right - to - left shunts , such as cyanotic congenital heart disease and severe liver cirrhosis ( where the pulmonary circulation is abnormal due to the development of arteriovenous connections in the lungs ) , these megakaryocytes and large platelet particles may bypass the lung and reach the distal extremities , leading to the interaction with endothelial cells .\nthis interaction in the distal portion of extremities would then result in degranulation and the production of platelet - derived growth factor ( pdgf ) and other factors , causing proliferation of connective tissue and periosteum .\nhoa has been associated with many different benign and malignant intrathoracic tumors and occurs in 510% of patients with intrathoracic malignancies including lung cancer and pleural tumors .\nthe most frequently associated cancer is non - small cell lung cancer . in these situations ,\nthe tumor itself may supply a vascular shunt from right to left without being filtered through pulmonary capillaries .\nmegakaryocytes are larger in lung cancer than normal and may have increased pdgf synthetic activity .\nthe relatively frequent association of hoa with lung cancers suggests that some additional factors may be involved in the development of hoa in lung cancer .\ngrowth hormone secretion by bronchogenic carcinoma was suggested for the underlying mechanism of the occurrence of hoa and clubbing .\nreported an elevated serum growth hormone level and growth hormone - releasing hormone ( ghrh)-producing cells in a non - small lung cancer patient with hoa . recently , vascular endothelial growth factor ( vegf ) has been implicated in the pathogenesis of hoa .\nsilveira et al . reported that plasma levels of vegf were significantly higher in patients with primary hoa and in those with lung cancer associated with hoa , compared with healthy control .\nin addition , serum vegf levels were higher in patients with lung cancer and hoa compared with lung cancer patients without hoa .\nthymic carcinoma is a rare epithelial neoplasm of the thymus that has a poor prognosis . in the past ,\ninvasive thymoma has a similar cytological feature to benign thymoma but thymic carcinoma exhibits malignant cytological features .\nthere has been no explanation for the mechanism of the coexistence of thymic carcinoma and hoa .\nreported that serum levels of vegf and basic fibroblast growth factor ( bfgf ) were significantly elevated in patients with thymic carcinoma compared with those in healthy volunteers .\ntherefore , the results suggested that serum vegf and bfgf might serve as markers for thymic carcinoma and these angiogenic factors could be associated with the invasiveness of thymic carcinoma . on the other hand , lauriola et al\nthus , we measured the serum level of vegf in the patient by using human vegf elisa ( enzyme - linked immunosorbent assay ) kit ( amersham pharmacia biotech , buckinghamshire , uk ) .\nserum vegf level was elevated in the patient ( 1,120 pg / ml ) compared with the mean value of healthy volunteers ( 388 68.9 pg / ml ) .\nwe also measured the serum level of the growth hormone in the patient . although it might not have significance because provocation and suppression tests were not done , the serum level of the growth hormone ( 5.6\nug / l ) was not increased compared with a normal control value ( < 10 ug / l ) .\nhowever , further study is warranted to evaluate the mechanism of hoa and the relationship between hoa and thymic carcinoma .\nthe patient was initially treated with external radiation therapy because of poor resectability and increased operative risk .\n, new metastatic brain lesion was observed in a brain mri that was performed when the patient complained of neurologic symptoms .\nbrain metastasis was known to be rare in thymic carcinoma , so it was also an unusual presentation of thymic carcinoma .\nbecause high serum vegf has been known to relate with metastasis and invasiveness of cancer and poor clinical outcome , brain metastasis might be associated with elevated serum vegf in the patient .\nconsidering the possible relationship between serum vegf and the development of hoa , it may be suggested that hoa could be a poor prognostic sign in thymic carcinoma . in summary , we experienced a rare case of poorly differentiated thymic carcinoma associated with hoa and suggest a possible association between thymic carcinoma and hoa .", "answer": "hypertrophic osteoarthropathy is characterized by clubbing and periosteal new bone formation along the shaft of the long bones of the extremities . \n although various intrathoracic malignancies have been associated with the development of hoa , it has been extremely rare for hoa to occur in a patient with a thymic carcinoma . \n recently , we experienced a 63-year - old woman diagnosed as a thymic carcinoma with hypertrophic osteoarthropathy . \n she had both digital clubbing and cortical thickening in her lower extremities identified radiologically . \n we herein describe this case with a review of the literature .", "id": 652} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe vertebrate immune system employs a wide variety of antigen - specific receptors - the immunoglobulins and t - cell receptors - to recognize and neutralize foreign invaders .\nthe receptor diversity necessary to recognize an almost limitless universe of potential pathogens is created by a site - specific dna rearrangement process termed v(d)j recombination .\nthis unique reaction assembles the receptor genes from separate v , d and j gene segments , a process ostensibly restricted to lymphocytes at a certain stage of their development . in this view\n, the prediction is that the germline dna of a given organism should contain unrearranged receptor genes ; rearranged versions of the genes should exist only in lymphocytes .\nthis prediction was satisfied by examination of germline and lymphocyte dna samples from a variety of familiar vertebrates , including mice , humans , birds , and common farm animals .\nthe fly in the ointment , however , appeared with an analysis of receptor genes in the germline of evolutionarily distant organisms - the cartilaginous fishes . in these primitive vertebrates ,\nmany of the immunoglobulin genes are actually found pre - rearranged in the germline ( reviewed in ) .\nthis suggests that the v(d)j recombinase may actually be an evolutionary force , a notion that is strongly supported by recent studies in the nurse shark .\nthe evolutionary consequences of these site - specific germline gene rearrangements may reach far beyond the immune system .\nthe recombination machinery recognizes dna sequences called recombination signal sequences ( rsss ) adjacent to each gene segment .\neach rss consists of conserved heptamer and nonamer motifs separated by 12- or 23-nucleotide ' spacer ' sequences .\nthe recombinase is made up of two proteins , rag-1 and rag-2 , which , in conjunction with the non - specific dna - bending proteins , hmg-1 or hmg-2 , recognize the rss and catalyze site - specific dna cleavage ( see for review ) .\ncleavage requires both rag-1 and rag-2 , and co - expression of these proteins is thought to be limited to developing lymphocytes ( , and reviewed in ) . as illustrated in figure 1 , the rag proteins introduce a double - strand dna break precisely between the v , d or j coding sequence and the rss , generating two types of dna ends : blunt signal ends ( which terminate in the rss ) and covalently sealed ( hairpin ) coding ends ( which terminate in the v , d or j element ) . after cleavage ,\nthe two signal ends are joined , producing a signal joint . prior to joining the coding ends ,\nthe hairpins must be opened ; joining generates a coding joint that may have lost or gained nucleotides .\nthe precise details of the end - processing and joining reactions remain obscure , and are not important for this story ; it is clear , however , that multiple , non - lymphoid - specific dna repair proteins are involved .\none detail that is important is that the opening of the hairpins frequently occurs ' off center ' , leading to palindromic single - stranded tails . joining of these ends can give rise to a characteristic signature in the completed junction : a palindromic , or p nucleotide , insertion .\nanother type of junctional insertion , n ( non - templated ) nucleotides , are added randomly by the enzyme terminal deoxynucleotidyl transferase .\nthus , coding joints formed by v(d)j recombination have several distinguishing characteristics , including variable loss of nucleotides and the frequent presence of either n nucleotides , p nucleotides , or both .\nv(d)j recombination bears many striking parallels to the movement of certain transposable elements , both in its general form and in important mechanistic details of the reaction ( reviewed in ) .\nin fact , recent biochemical experiments have shown that purified rag proteins can catalyze transposition in the test tube , integrating a dna fragment bearing signal ends into a target duplex ( figure 2 ) .\nthis reaction does not require specific dna sequences in the target and , like many transposition reactions , creates a characteristic ' footprint ' : upon integration , three to five nucleotides of target dna are duplicated on either side of the transposon .\nit should be noted that there is , as yet , no firm evidence that rag - mediated transposition events can occur in living cells .\nearly on , it was suggested that the v(d)j recombination system might have arisen by the fortuitous integration of a transposable element into an ancestral antigen - receptor gene .\nthis hypothesis was strengthened by the discovery that the rag genes are tightly linked , and by the finding that the rag proteins can act as a transposase .\nthus , a plausible model for the acquisition of the v(d)j recombination system during vertebrate evolution is the integration of a transposable element carrying the linked rag genes into a primordial antigen - receptor gene in an ancestral jawed vertebrate , approximately 450 million years ago ( reviewed in ) .\npresumably , this initial integration event created the first rearranging antigen - receptor gene ; subsequent gene duplication events then created the multiple immunoglobulin and t - cell receptor loci . to learn more about the evolutionary origins of the combinatorial immune system ,\nseveral laboratories have characterized antigen - receptor loci from a wide variety of species , including the cartilaginous fishes - the living jawed vertebrates most phylogenetically distant from mammals .\nthe immunoglobulin loci of sharks and skates contain some fairly typical antibody genes , with multiple v , d and j elements .\nsurprisingly , however , many of the immunoglobulin genes are already partially or fully rearranged in the germline ( see for review ) .\nrecently , pre - rearranged immunoglobulin genes were also found in a teleost fish , the channel catfish .\none possibility is that they are descendants of the ancestral antigen - receptor gene , before integration of the putative transposable element .\na second possibility is that these genes arose from rag - mediated dna rearrangement events that occurred in the germline , an operation that violates the precept that the rag recombinase is functional only in developing lymphocytes . a recent paper by lee et al\n. addresses these questions by examining immunoglobulin genes in the nurse shark . the nurse shark ns4 immunoglobulin light chain gene family provided very useful information , as there are several highly homologous genes present both in pre - rearranged and unrearranged forms .\nthese features allowed the authors to evaluate sequences in sufficient detail to ascertain whether the genes bear characteristic features of v(d)j recombination or footprints of transposition .\ntheir analysis revealed that the pre - rearranged genes did indeed contain tell - tale signs of coding joints formed by v(d)j recombination , including both n nucleotides and p nucleotides , which strongly suggest a hairpin intermediate .\nthe presence of these features in several junctions suggests several independent germline v(d)j recombination events , although analysis of multiple unrelated individuals suggests that these events are not frequent .\nimportantly , analysis of the unrearranged ns4 genes failed to detect the target site duplications that are hallmarks of transposon insertions .\nthus , while the pre - rearranged ns4 genes appear to have been derived from unrearranged genes by germline v(d)j recombination , there is as yet no evidence to support the hypothesis that the unrearranged genes were derived from the pre - rearranged genes by insertion of a transposable element ; this is discussed in a recent review by lewis and wu .\nthe recent studies of the nurse shark ns4 genes strongly suggest that v(d)j recombination events can occur in the germline .\nmoreover , phylogenetic analysis indicates that these events occurred recently ( at least from an evolutionary perspective ) , some time within the last 7 million years . what evolutionary benefit might there be in germline recombination events ?\npre - rearranged immunoglobulin genes may confer certain advantages over genes that must be assembled by recombination in individual lymphocytes .\nfor example , pre - rearranged genes may encode receptors capable of recognizing common pathogens likely to be encountered during the neonatal period , before the development of a full repertoire of rearranged antigen receptors .\nfurthermore , germline joining could have contributed to evolution of gene segment clusters , and possibly the evolution of d segments .\nto my knowledge , co - expression of both rag proteins outside the lymphoid system has not been reported , but rna species encoding rag-1 and rag-2 have been detected in zebrafish ovary and xenopus oocytes , respectively . even if the recombinase is not normally expressed in these tissues , though , inappropriate expression might occur occasionally , perhaps as a result of improper reprogramming of tissue - specific gene expression during development .\nif rag expression does occur during the development of germ cells , another important question arises : how are loci chosen for rearrangement ? during normal b - lymphocyte differentiation , immunoglobulin loci undergo a carefully orchestrated series of rearrangements .\nd to j rearrangements of the heavy - chain genes occur first , followed by v to dj rearrangements , followed in turn by rearrangement of the light - chain genes .\nthe carefully ordered sequence of rearrangements is critical for proper lymphocyte differentiation and is thought to be controlled by accessibility of the loci , mediated by alterations in chromatin structure ( reviewed in ) .\nrsss present in antigen - receptor loci that have not been ' targeted ' for rearrangement are used rarely , if at all .\nthe careful control of locus accessibility seen in lymphocyte differentiation may not be recapitulated in the development of germ cells - after all , these cells are not supposed to be expressing rag recombinase activity . furthermore , the v(d)j recombinase is not particularly picky about the sequences it can target for rearrangement .\nlewis and co - workers have found that ' cryptic ' sites capable of supporting rearrangement occur at least once in every 600 base pairs of a commonly used plasmid sequence , and they have estimated that there are at least 10 million such sites in the mammalian genome .\nin fact , there is evidence that cryptic sites in the mammalian genome can serve as targets for rag - mediated rearrangement in lymphocytes ( reviewed in ) .\nthus , it is possible that rag expression during germ - cell development might cause rearrangements of regions of the genome far removed from the immune receptor loci .\nthese considerations suggest that the v(d)j recombinase might have been ( and could still remain ) a significant force shaping vertebrate evolution , by catalyzing v(d)j - like rearrangements and , perhaps , transposition .\ncomparison of genome sequences from a variety of organisms may allow some aspects of this notion to be tested .\nfirst , the rag proteins bind to the rsss ( triangles ) and bring them together into a synaptic complex .\ncleavage ensues , generating a pair of blunt signal ends and a pair of dna hairpin coding ends . joining of these ends generates signal and coding joints , respectively .\na fragment of dna generated by rag - mediated cleavage , with rag proteins bound to the signal ends ( the donor ) , can capture another dna duplex ( the target ) .\nthe rag proteins bound to the signal ends catalyze integration into the target , generating a characteristic duplication of the target sequence at the integration site ( arrowheads ) .\ni thank vicky brandt for editorial assistance and mark landree for critical comments on the manuscript .\nwork in the author 's laboratory is supported by the howard hughes medical institute and by grants from the national institutes of health , the human frontiers science program , and the american cancer society .", "answer": "the antigen - receptor genes of vertebrates are rearranged by a specialized somatic recombination mechanism in developing lymphocytes - and , unexpectedly , also in the germline of cartilaginous fishes . \n the recombination system that carries out these dna rearrangements may thus be a significant evolutionary force , perhaps not limited to rearrangements at antigen - receptor loci .", "id": 653} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbesides its classical role in calcium and bone homeostasis , vitamin d is considered a potent immunomodulator that can affect the pathogenesis of several autoimmune diseases .\nour aim is to evaluate the effect of vitamin d correction to a patient with new onset graves disease ( gd ) with an underlying vitamin d deficiency .\nwe describe the effect of vitamin d3 on untreated graves disease with vitamin d deficiency .\na healthy saudi woman in her 40s sought consultation with a three - month history of palpitation .\nshe denied any history of heat intolerance , weight loss , menstrual irregularity or sweating .\n. physical examination revealed a mild diffusely enlarged and non - tender thyroid gland with no bruit .\nthe initial thyroid function test , which was done in an outside hospital , revealed a tsh , 0.01 miu / l ; ft4 , 22.5\nvitamin d 25-oh level was done in our hospital and showed a result of 26.0 nmol / l with a tsh , 0.013 miu / l ; ft4 , 16.7\ntc-99 m thyroid scintigraphy demonstrated an enlarged thyroid gland with increased radiotracer trapping and heterogeneous distribution .\nthe patient was given only oral cholecalciferol 4000 iu per day since november 2012 ( prescribed by an outside hospital ) then from may 2013 onwards she was given 50,000 iu per month .\nfollow - up laboratory exams revealed improved vitamin d levels as well as tsh and ft4 .\nvitamin d deficiency may exacerbate the onset and/or development of gd and correction of the deficiency may be able to reverse it .\nhowever , further prospective clinical studies will be needed to define the role of vitamin d treatment in gd .\nmore recently , vitamin d has been shown to be a modulator in both innate and adaptive immunity.1 there is a well - established link between vitamin d deficiency and various autoimmune diseases , including type 1 diabetes mellitus ( t1 dm ) , systemic lupus erythematosus ( sle ) , rheumatoid arthritis ( ra ) , inflammatory bowel disease ( ibd ) , and multiple sclerosis ( ms ) .\nfurthermore , it has been found that the supplementation of vitamin d can prevent the onset and/or development of different kinds of autoimmune disorders in human beings and animal models.2 in addition , it has been shown that the prevalence of vitamin d deficiency is common in patients with graves disease ( gd),3 and is associated with higher thyroid volume.4 in our case report , we evaluated the effect of vitamin d correction to a patient with new onset gd with an underlying vitamin d deficiency .\na healthy saudi woman in her 40s sought consultation with a 3 months history of palpitation .\nshe denied any history of heat intolerance , weight loss , menstrual irregularity , diarrhea , or sweating .\nthere was no personal or family history of thyroid disease and no specific medication history .\nphysical examination revealed a mild diffusely enlarged and non - tender thyroid gland with no bruit .\nthe initial thyroid function test , which was done in an outside hospital , revealed a tsh , 0.01 miu / l ; ft4 , 22.5\nvitamin d 25-oh level was done in our hospital and showed a result of 26.0 nmol / l with a tsh , 0.013 miu / l ; ft4 , 16.7\nanti - thyroid antibodies showed a tg , 17.1 iu / ml ; tpo , 0.19 iu / ml with a positive tsh receptor antibody .\ntc-99 m thyroid scintigraphy demonstrated an enlarged thyroid gland with increased radiotracer trapping and heterogeneous distribution ( fig .\nthe patient was given only oral cholecalciferol 4000 iu per day since november 2012 ( took it from an outside hospital ) then from may 2013 onwards she was given 50,000 iu per month .\nthe serial thyroid function tests , vitamin d levels , and titer autoantibodies are summarized in table 1 .\nfollow - up laboratory exams revealed improved vitamin d levels as well as tsh and ft4 .\nwritten informed consent was obtained from the patient for the publication of this case and accompanying images .\nit has become apparent that multiple factors contribute to the etiology of gd , including genetic and environmental factors .\nthese activated t cells in turn increase the secretion of thyroid - specific autoantibodies from b cells .\nthe prevalence of vitamin d deficiency was reported to be common in patients with gd.3 whether vitamin d deficiency has a causal relationship with gd remains a controversial issue .\nmisharin et al.5 observed that vitamin d deficiency was found to modulate graves hyperthyroidism induced in balb / c mice by thyrotropin receptor immunization . in this study ,\nbalb / c mice on a vitamin d deficient diet were more likely to develop persistent hyperthyroidism than other mice receiving adequate vitamin d supply . in another study ,\ncombination treatment with methimazole and vitamin d3 ( 1,25 ( oh)2d ) in patients with gd has more rapid euthyroidism achievement compared with patients receiving methimazole alone.6 in addition , vitamin d supplementation has been shown to inhibit inflammatory responses in human thyroid and t cells.7 interestingly , vitamin d deficiency is found to be associated with higher thyroid volume in patients with newly onset gd.4 it has been recently discovered that vitamin d - receptor gene and vitamin d - binding protein gene polymorphisms are associated with gd.8,9\nour present case supports the current literature and strongly suggests that vitamin d deficiency may exacerbate the onset and/or development of gd and correction of which may be able to reverse it .\nhowever , further prospective clinical studies will be needed to define the role of vitamin d treatment in gd .", "answer": "objectivebesides its classical role in calcium and bone homeostasis , vitamin d is considered a potent immunomodulator that can affect the pathogenesis of several autoimmune diseases . \n our aim is to evaluate the effect of vitamin d correction to a patient with new onset graves disease ( gd ) with an underlying vitamin d deficiency.methodwe describe the effect of vitamin d3 on untreated graves disease with vitamin d deficiency.resultsa healthy saudi woman in her 40s sought consultation with a three - month history of palpitation . \n she denied any history of heat intolerance , weight loss , menstrual irregularity or sweating . \n she has a history of chronic muscle aches and pains . physical examination revealed a mild diffusely enlarged and non - tender thyroid gland with no bruit . \n she had no signs of graves ophthalmopathy . in laboratory examinations , \n the initial thyroid function test , which was done in an outside hospital , revealed a tsh , 0.01 miu / l ; ft4 , 22.5 \n pmol / l and ft3 , 6.5 pmol / l . \n vitamin d 25-oh level was done in our hospital and showed a result of 26.0 nmol / l with a tsh , 0.013 miu / l ; ft4 , 16.7 \n pmol / l ; and ft3 , 3.8 pmol / l . \n tsh receptor antibody was positive . \n tc-99 m thyroid scintigraphy demonstrated an enlarged thyroid gland with increased radiotracer trapping and heterogeneous distribution . \n the patient was given only oral cholecalciferol 4000 iu per day since november 2012 ( prescribed by an outside hospital ) then from may 2013 onwards she was given 50,000 iu per month . \n follow - up laboratory exams revealed improved vitamin d levels as well as tsh and ft4 . \n she eventually improved both clinically and biochemically with a satisfactory outcome.conclusionvitamin d deficiency may exacerbate the onset and/or development of gd and correction of the deficiency may be able to reverse it . \n however , further prospective clinical studies will be needed to define the role of vitamin d treatment in gd .", "id": 654} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nallergic rhinitis ( ar ) is a recurrent or chronic allergen specific , ige - mediated hypersensitivity disorder affecting the nasal lining and characterized by nasal congestion , rhinorrhea , sneezing , nasal itchiness , and/or postnasal drip .\nlimited studies on ar exist and epidemiological studies based on the allergic rhinitis and its impact on asthma ( aria ) criteria are lacking . according to aria guidelines , allergic rhinitis is defined if two or more symptoms of rhinorrhea , nasal itching , nasal blockage , or sneezing are present in a patient for at least one hour per day for 4 days or more a week and also for 4 or more weeks a year . based on duration ,\nsymptoms are intermittent ( < 4 days / week or < 4 weeks / year ) or persistent ( > 4 days / week or > 4 weeks / year ) .\nseverity grading is either mild or moderate - severe based on the absence or presence of sleep disturbance and impairment in daily activities , school , and work , respectively .\nskin prick test ( spt ) is a standardized test widely used in the diagnosis of suspected cases of ige - mediated allergy .\ngenerally accepted indications for spt include allergic rhinitis , asthma , atopic dermatitis , suspected food allergies , latex allergy , and conditions in which specific ige is suggested to play a role in the pathogenesis .\nit provides information about the presence of specific ige to protein and peptide antigens ( allergens ) .\nidentification of common aeroallergens in an area is necessary , in order to educate the patient on what allergens to avoid and also help find the best formulation of allergen immunotherapy for effective ar treatment . to date\n, there has been no information regarding the common allergen from the federal capital territory ( fct ) of nigeria , abuja .\nthe aim of this study is to identify the clinical profile of ar patients according to aria guidelines and investigate the common allergens in abuja , nigeria .\nthis cross - sectional study was conducted for a period of 18 months ( march 2014 to september 2015 ) .\nsample population was based on the ar patients referred to the allergy clinic , affiliated to medicaid radiodiagnostic center , wuse 2 , abuja .\npatients were consecutively recruited ( convenient sampling method ) and fall within the age range of 5 to 65 years .\nthey were patients with a positive history of nasal inflammation ( at least 2 or more of the following symptoms : rhinorrhea , sneezing , nasal blockage , nasal itchiness , and postnasal drip ) for at least one - year duration .\npatients ' symptoms were categorized as sneezers - runners and blockers based on the predominant complaint . patients\nwhose chief complaints include sneezing , rhinorrhea , and itchy eyes and nose were classified as sneezers - runners , while those with nasal blockage , postnasal drip , and difficulty with breathing were classified as blockers . \nspt was performed on patients who have stopped taking antihistamines at least 5 days before the test , while patients with severe dermatographism were excluded from the study .\na total of 22 allergens were used in this study ; these allergens make up the subtropical prick test batch of alk - abello , denmark .\nthese include tree pollen ( oak , pecan , black willow , pine , cypress , red cedar , and box elder ) , weed pollen ( pigweed , ragweed , and plantain ) , grass pollen ( bermuda , bahia , johnson grass , and grass mix ( meadow , orchard , timothy , june , rye , and redtop ) ) , house dust mites ( dermatophagoides pteronyssinus and dermatophagoides farinae mix ) , molds ( alternaria tenuis , c. cladosporioides , penicillium mixed , and aspergillus mixed ) , animal dander ( cat hair and dog epithelium ) , and cockroach extracts . of the pollen allergen\nused in this study , about 80% of the plants are present in abuja environment .\nspt was performed according to international guidelines as a one - time test done on two forearms with lancets and allergens ( alk - abello skin prick test kit , berge alle , 2970 hrsholm . ,\nhistamine hydrochloride ( 1% ) and normal saline ( 0.9% ) were used as positive and negative controls , respectively .\nthe patients ' data was classified according to the aria guidelines and spt results were analysed in allergen - clusters of tree pollen , weed pollen , grass pollen , house dust mites ( hdm ) , molds , animal dander , and cockroach extracts .\nspss 16 software ( chicago illinois ) was used in the analysis and p value of less than 0.05 was considered significant .\na total of 96 new patients with suspected allergic rhinitis presented at the allergic clinic within the study period .\nonly 74 patients from these had a positive spt result and were enrolled into the study .\ntwenty - one respondents ( 28.4% ) were categorized as children ( 5 to 17 years of age ) with a male : female ratio of 1.3 : 1 .\nthe majority of the study population resided in abuja municipal area council ( amac ) territory which is basically the city center . \n\nthe prevalence of asthma , urticaria , and conjunctivitis as comorbidity was lower when compared with comorbidity such as hypertension .\npositive family history of atopy was seen in 56.8% of patients and 20.2% of the subjects had animal contact within their environment . according to predominant symptoms , the proportion of sneezers - runners was higher than blockers \n sneezers - runners tend to have persistent ar , while blockers symptoms were more intermittent ( p = 0.007 ) .\nbased on aria guidelines , most patients ( 67.2% ) had moderate - severe ar ( intermittent and persistent ) and this was significantly related to animal exposure ( p = 0.035 ) and not to age , gender , or family history of atopy .\nthere was a significant association between ar severity and the predominant complaints ( table 2 ) by the patients ( p = 0.005 ) .\nmoderate - severe persistent ar was more common among sneezers , while moderate - severe intermittent ar was common with the blockers .\n there was no significant association between ar severity and the presence of asthma ( p = 0.26 ) or family history of atopy ( p = 0.19 ) .\nhouse dust mites allergen yielded the highest number of positive responses ( 22.6% ) followed by tree pollen ( 16.8% ) .\nweed pollen allergen yielded the least ( 7.4% ) , while animal dander and fungi allergen both came to 13.1% each ( figure 1 ) .\nalso , house dust mites was significantly related to a positive family history of atopy ( p = 0.035 ) .\nthere was no significant difference between the positive skin tests and gender as well as history of asthma .\nfurthermore , no relationship was observed between the allergens tested and duration of ar ( intermittent and persistent ) , as shown in table 3 .\nmost of the patients with a positive spt were in the persistent ar category ( 66.2% ) .\nthe number of allergens which produced a positive skin response from each patient was closely distributed .\nthe highest was reaction to 3 or more allergens ( 35.1% ) followed by reaction to 2 allergens ( 33.8% ) and then to one allergen ( 31.1% ) , as shown in table 4 .\nstatistical analysis did not reveal a relationship between ar severity and skin prick test reactivity .\nthe prevalence of ar is increasing worldwide , yet it remains underdiagnosed and undertreated especially in developing countries .\na self - reported survey of ar among adult nigerians observed a prevalence of 29.6% and a mean age of 29.3 years which was close to the mean age observed in this study . the number of patients in this study with concomitant asthma is lower than other nigerian studies [ 7 , 8 ] and this could be due to small sample size or poor awareness of asthma symptoms by the respondents .\n. observed a low level of awareness of asthma by patients in nigeria , such that most people with asthma symptoms do not present to the physician but prefer unorthodox means of medical care . about a third of the children ( 33% ) in this study reported persistence or recurrence of rhinitis symptoms after adenoidectomy .\nthe slight female predominance observed in our adult ar patients is in consonance with the findings in malaysia and india [ 3 , 5 ] .\nwe also corroborated the study that showed a higher male predominance of ar among children .\nwe recorded a higher proportion of sneezers - runners to blockers similar to the findings by lee et al . and shah and pawankar but different from study by deb et al .\nsneezers having persistent ar and more blockers having intermittent ar ( p = 0.007 )\n. we could not establish any relationship between these predominant symptoms and the aeroallergens used in this study .\nblockers were more sensitized to hdm , house dust , and fungi , while \nthis study observed that a majority of ar patients were categorized as moderate - severe persistent ar , according to aria classification , while the least were mild intermittent ar .\nthis has been observed by most studies [ 3 , 5 , 12 ] with warm climate like nigeria .\na constantly high environmental temperature and humidity could lead to a persistently high concentration of indoor and outdoor allergens all year round .\nthere could also be a selection bias , since patients would more likely present for treatment when their condition is severe and persistent .\nno relationship was established between the type of ar and the allergen to which the patients were sensitized .\nthis was similarly observed in a national , cross - sectional study of ar patients in mexico .\nthe most common aeroallergen was house dust mites , followed by tree pollen as was seen in other spt studies in nigeria [ 8 , 1416 ]\n. however , there are no ar studies in relation to tree pollen sensitivity to compare with .\nthis study highlights the importance of pollen allergens among ar patients living in nigeria , a tropical country with high humidity .\nthis supports an earlier observation of increased tree pollen sensitization in tropical environment and emphasizes the need for increased research in this aspect .\nfurther studies are needed to record the season of pollination of the different pollens found in abuja and to correlate these findings with the timing of symptoms in sensitized patients .\nthus a patient with positive sensitization to house dust mites could also be sensitized against pollen , insect , or fungi allergens .\nthis supports the argument that time of exposure ( seasonal or perennial ) does not properly define ar patients and also creates difficulty with regard to immune therapy via hyposensitization .\nin addition , there is need for the use of spt that incorporates wide variety of allergens within a specific environment in order to avoid skipping some of the sensitive allergens attributed to each individual .\n, most ar patients presenting for treatment in abuja , nigeria , have moderate - severe persistent ar and show similar spt sensitization pattern with other countries having similar climatic conditions .\nsensitization patterns are not related to aria classification or any predominant ar symptoms but rather may rely on the environmental condition of study area and genetic makeup of the study population .", "answer": "allergic rhinitis ( ar ) is prevalent in nigeria , though little information exists on the allergen . \n we assessed the clinical features of ar patients in our environment based on the allergic rhinitis impact on asthma ( aria ) classification . \n only patients with positive skin prick test ( spt ) were recruited . \n seventy - four patients participated in the study . \n ar and asthma comorbidity were observed in 13.5% . \n the proportion of sneezers - runners was higher than blockers with significantly more \n sneezers - runners having persistent ar ( p = 0.007 ) . \n no relationship was established between these predominant symptoms and the aeroallergens used in this study . \n intermittent mild and moderate / severe ar were evident in 13.5% and 31.1% , while persistent mild and moderate / severe were seen in 20.3% and 35.1% , respectively . \n house dust mites allergen yielded the highest number of positive responses ( 22.6% ) followed by tree pollen ( 16.8% ) . \n no relationship was observed between the allergens tested and ar severity . \n majority of patients were oligosensitive ( 33.8% ) and polysensitive ( 35.1% ) and were not significantly associated with ar severity ( p = 0.07 ) . \n most ar patients presenting for treatment in abuja , nigeria , had moderate - severe persistent ar and showed similar spt sensitization pattern with countries having similar climatic conditions . \n sensitization patterns were not related to aria classification or predominant ar symptoms .", "id": 655} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 47-year - old lady presented to us for evaluation of persistent hydroureteronephrosis on imaging .\n3 months earlier , she had been treated at another center for a 3 month history of right colicky flank pain associated with malaise and fever , without any lower urinary tract symptoms .\ninvestigations at that time showed raised creatinine ( 4.8 mg / dl ) and bilateral hydroureteronephrosis on ultrasonography .\nshe was treated with antibiotics for suspected pyelonephritis and serum creatinine showed a downward trend , reaching a nadir creatinine of 1.41 mg / dl over the next 3 months .\nher medical history was significant for diabetes for 8 years , hypothyroidism for 4 years and hypertension for 3 years .\nevaluation at our centre revealed 2 - 4 red blood cells and 6 - 8 white blood cells in the urine . computed tomography ( ct urography ) showed bilateral hydroureteronephrosis with global caliectasis , right and left ureter were dilated till s1 and l5 vertebral level respectively , at which point there was a hyperdense enhancing lesion within the ureteric lumen , associated with ureteric wall thickening , periureteric and retroperitoneal fat stranding and normal ureteric caliber below this level .\nshe was planned for cystoscopy and bilateral retrograde pyelography but required emergency bilateral percutaneous nephrostomy for sudden onset anuria , breathlessness , azotemia ( serum creatinine 11.1 mg / dl ) , hypertensive crisis ( blood pressure 210/110 ) and flash pulmonary edema .\nshe had post obstructive diuresis and the creatinine level reached a nadir of 1.53 mg% at 2 weeks .\ncystoscopy and retrograde pyelography revealed bilateral mid - ureteric narrowing [ figure 2 ] , which persisted on balloon dilatation .\na ureteroscope could be negotiated till the lower level of narrowing on both sides and revealed mildly edematous urothelium ; no obvious luminal lesion was identified .\nintramural pathology compressing the ureteric lumen symmetrically on both sides was considered , and she was taken up for laparotomy and frozen section histology .\nvenous phase of contrast - enhanced computed tomography of abdomen and pelvis showing : ( a ) bilateral global dilatation of calyces and pelvis , ( b and c ) red and blue arrows showing right and left ureters respectively , ( d ) showing normal urinary bladder retrograde pyelography done before ureteroscopy : ( a and b ) showing filling defect in right ureter at level of upper sacroiliac joint , both proximal and distal ureter are well opacified with radio contrast , ( c ) showing filling defect in left ureter , faint opacification of proximal ureter is seen at upper sacroiliac joint on laparotomy , the left ureter was found to be thickened and fibrotic from l5 to s1 vertebral level ; similarly , right ureter was thickened and necrotic from l5 to s3 level , retroperitoneal tissue around these ureters was grossly normal .\nfrozen sections from the ureteric wall on both sides were reported as caseating granulomatous inflammation and later confirmed on routine histopathology .\nan ileal segment was used to replace the involved ureteric segments from l3 level to the bladder and she was started on 4 drug antitubercular therapy ( att ) , with which she showed clinical improvement ( absence of fever , malaise and flank pain ) .\nsix months later , creatinine was 0.66 mg% and follow up ultrasound of abdomen 6 months and 18 months post surgery showed resolution of bilateral hydronephrosis .\nshe was continued on att beyond 6 months as evaluation for headache revealed an intracranial right cavernous sinus lesion which was not amenable to biopsy and was presumed to be tubercular in etiology .\nbilateral synchronous mid - ureteric lesions are rare and may be congenital , or iatrogenic , following radiotherapy or aortic aneurysmal surgery .\nbilateral ureteric involvement with acute renal injury has been described due to radiation - induced mid- and lower ureteric strictures ; however , bilateral synchronous mid - ureteric tubercular strictures without obvious radiological renal or bladder involvement as a cause for acute renal injury has not been described in literature .\nurinary system involvement in tuberculosis is commonly unilateral , probably due to delayed reactivation of a solitary focus .\nureteric involvement is considered secondary to renal involvement , with the vesicoureteric junction being the most commonly involved .\ntuberculosis usually involves the intramural part of the ureteric wall and is characterized by ureteric thickening and post contrast ureteric wall enhancement on contrast - enhanced computed tomography . bilateral involvement with renal failure\nis commonly seen after descending infection from one renal unit involving the bladder and subsequent contralateral unit damage due to vesicoureteric reflux and/or small capacity poorly compliant bladder .\nthis case is unique in many respects and can not be easily explained by accepted theories on the etiopathogenesis of urinary tuberculosis .\nthere was bilateral , synchronous involvement of the mid - ureter , which , according to existing literature , is the least commonly involved ureteric segment in urinary tb .\nthis can only be explained by taking into account the following facts : bilateral pathological involvement of the urinary system via hematogenous route is not unusual ; in fact , a seminal study by medlar found bilateral pathological involvement to be the rule , rather than the exception and renal tuberculosis can be clinically silent .\ninvolvement of bilateral ureteric segments either by direct hematogenous spread or following bacilluria from an undetectable renal lesion and subsequent simultaneous activation can explain the findings of the case .\nthe interaction between host immunity and pathogenicity decides the clinical presentation . at one end of spectrum\nis the activation of a single focus of tuberculosis even in the presence of multiple tubercular pathological foci and at the other end is disseminated tuberculosis where more than one tubercular foci become clinically apparent simultaneously . in the case\ndescribed above , the simultaneous clinical activation of two pathological foci and later on presentation of an intracranial lesion suggests this patient 's immune response lay somewhere midway along the spectrum .\nthe presence of caseating necrotizing granulomatous inflammation is almost always associated with tuberculosis and rarely with nocardiosis ( where granuloma formation is rare ) ; however , the clinical features ( no solid organ abscesses , response to att ) are not consistent with the latter . if tuberculosis had been entertained as a differential diagnosis , appropriate microbiological work up could have been initiated and if proven positive , the patient would have benefited from a 4 to 6 week course of anti - tubercular therapy prior to treatment for ureteric stricture , if it failed to resolve with medical therapy .", "answer": "a young female presenting with right flank pain , fever , raised creatinine and bilateral hydronephrosis was treated with antibiotics elsewhere , with presumptive diagnosis of bilateral pyelonephritis . \n she had partial relief in symptoms and her creatinine level showed an improvement . \n three months later during evaluation at our center she had anuria , hypertensive crisis and pulmonary edema which were managed with emergency bilateral percutaneous nephrostomies . \n cross - sectional imaging and ureteroscopy suggested bilateral synchronous intramural mid - ureteric lesions as underlying pathology . \n histopathology of the ureteric segments during laparotomy revealed caseating granulomas suggestive of tuberculosis . \n this clinical presentation has not been previously described in urinary tuberculosis .", "id": 656} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncorynebacterium urealyticum , a gram - positive bacillus , has been identified as the most frequent causative pathogen .\nurinary stasis is highly likely to contribute to stone formation , because large - scale spontaneous precipitation of crystals occurs when a critical concentration ( e.g. , supersaturation ) is exceeded .\nfailed treatment of encrusted pyelitis in a transplanted kidney can cause graft failure or nephrectomy . to overcome urinary stasis with encrusted pyelitis in a transplanted kidney , we report surgical treatment by ileo - pelvic anastomosis without nephrectomy .\nin addition , in this case , augmentation cystoplasty was performed to strengthen the atrophied bladder following tuberculosis .\na 51-year - old female patient received a kidney from her sister after a double nephrectomy owing to renal tuberculosis 12 years previously . at that time , the transplanted ureter was anastomosed to the ileum in the left lower abdomen with an ileal conduit on the opposite side .\nthe patient experienced no problems for 12 years . at a routine checkup , she complained of abdominal pain , gross hematuria , and increased debris in the ileal conduit .\nher serum creatinine was elevated to 1.7 mg / dl ( normal , 0.6 to 1.1 mg / dl ) , and her transplanted kidney developed hydronephrosis with calcified debris observed by sonography ( fig .\nneither hydronephrosis nor calcified debris had been observed 6 months before in a routine outpatient checkup .\nabdominopelvic computed tomography revealed hydronephrosis with encrusted pyelitis and ureteritis in the transplanted kidney ( fig .\na cystogram showed that the bladder was not refluxed but had a small capacity ( 50 ml ) .\nafter 3 weeks , we operated to anastomose the transplanted renal pelvis to one end of the ileal conduit , performing augmentation cystoplasty with new ileum and to anastomosis the other end of the remnant ileum with the augmented bladder .\naugmentation cystoplasty is a reconstructive technique for creating a compliant , large - capacity urinary storage unit to protect the upper urinary tract .\nthe operation was performed via a midline incision . because it was difficult to approach the major calices of the transplanted kidney in the left pelvic rim\n, we anastomosed one end of the ileal conduit to the pelvis of the transplanted kidney in an end - to - end fashion .\nthe ileal conduit was lengthened by 30 cm to extend from the pelvis to the augmented bladder chimney .\nafter exposure of the urinary bladder , a transverse wide v - shaped cystostomy incision was created , with the apex approaching the anterior bladder neck and the base extending posteriorly past the midcoronal plane of the bladder dome .\na 20 cm segment of new ileum at least 15 cm proximal to the ileocecal junction was used for ileocystoplasty . for the small bowel ,\na v - shaped plate was created by a side - to - side anastomosis with 2 - 0 vicryl .\na circumferential , continuous , full - thickness , single layer anastomosis of the bowel to the bladder was started posteriorly by using 2 - 0 braided absorbable sutures .\nthe other end of the ileal conduit was anastomosed through small separate ileotomies ( 1.5 cm length ) in the limb of the augmentation cystoplasty .\na follow - up cystogram showed increased bladder capacity to approximately 300 ml with well - preserved end - to - end anastomosis of the ileo - pelvic portion with the other end of one chimney of augmentation cystoplasty with the elongated ileal conduit ( figs . 3 , 4 ) .\nthe most common causative agent in the formation of infection stones is a urease - positive urinary tract infection .\nless invasive methods are preferable to preserve the connection between the renal pelvis and the upper ureter .\nileo - pelvic anastomosis must be adjusted for patients with infection stones in the upper urinary tract after renal transplantation . an alternative way to prevent these infection stones\nis to ensure a wider pathway through a ureter that has been narrowed in places by these stones . according to a report on the incidence of urolithiasis in cystectomy patients , 5 of 78 patients who had undergone diversion with an intestinal conduit developed urolithiasis , all in the upper tract .\nin contrast , 4 of 78 patients who had received a diversion had a renal stone at the time of presentation\n. refluxing urine may contribute to an increased risk of stone formation after urinary diversion , whereas pouch stasis may contribute to stone formation in the diversion group .\na case of failed treatment of encrustation in a kidney transplant recipient was reported and graft removal was performed after 6 months of failed management owing to intractable febrile urinary tract infections that became life threatening .\nthey excised renal parenchyma from the caudal portion of the inferior calyx , which was then anastomosed to the ileostomy . in their case ,\nbladder capacity was within the normal limit ; thus , augmentation cystoplasty was not indicated . in conclusion , if urinary tract infection is controlled , we suggest that ileo - pelvic anastomosis combined with augmentation cystoplasty is an alternative for the treatment of encrusted pyelitis with atrophied bladder . in our patient , we performed ileo - pelvic anastomosis to prevent urinary stasis by elongating the ileal conduit .\nin addition , the augmentation cystoplasty technique is useful for increasing bladder capacity that has been diminished by renal tuberculosis ( fig .", "answer": "infection stones are more likely to form after urinary diversion as the result of urinary stasis . to prevent urinary stasis due to encrusted pyelitis in a transplanted kidney \n , we describe an alternative a surgical treatment : ileo - pelvic anastomosis . in our patient with a transplanted kidney , \n the ileal conduit had previously been anastomosed end - to - side owing to renal tuberculosis with an atrophied bladder ; the transplanted ureter was anastomosed to the ileum in the left lower abdomen with an ileal conduit on the opposite side . \n routine check - up revealed hydronephrosis with infected pyelitis and ureteritis in the transplanted kidney . \n we performed ileo - pelvic end - to - end anastomosis to prevent urinary stasis by lengthening the ileal conduit and performed augmentation cystoplasty to support the atrophied bladder following tuberculosis . \n we suggest that this approach may be useful in similar cases .", "id": 657} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe anterior choroidal artery ( achoa ) supplies several important structures including the optic tract , geniculate body , posterior limb of internal capsule , globus pallidus , cerebral peduncle , uncus , amygdala , ventrolateral nucleus of thalamus , and choroid plexus .\nthe vascular injury of achoa may result in severe neurological deficits such as hemiplegia , hemianesthesia , hemianopsia , decreased consciousness , and extrapyramidal symptoms .\ntherefore , complete knowledge about vascular anatomy of achoa is very important before surgical or endovascular manipulations .\nalthough several detailed reports about anatomical variations of achoa have been reported , transposition of achoa as to posterior communicating artery ( pcoma ) origin was demonstrated only in 3 reports2 - 4 ) .\nwe report a case with ruptured cerebral aneurysm arising from pcoma , which originated from the internal carotid artery ( ica ) distal to the origin of achoa .\na 40-year - old woman presented with sudden onset of headache . computed tomography ( ct ) revealed subarachnoid hemorrhage ( sah ) which was slightly predominant in the left basal and sylvian cisterns .\ntwo small aneurysms arose from both distal supraclinoid ica , these were observed on ct angiograms ( fig .\ncerebral angiography demonstrated a small aneurysm arising from left fetal type of pcoma with suspicion of rupture and the other small aneurysm originating from right pcoma or perforating branch of ica . in this study , left achoa originated from ica proximal to the origin of fetal type of pcoma ( fig .\nachoa usually arises from the posterolateral wall of ica , a few mm distal to the origin of pcoma , and it provides blood supply to the important neural structures around crural and ambient cisterns .\nthe achoa can have several variations in the course , size , number , branching pattern , and brain region supplied by this artery1 ) . among them\n, there have been several anomalies related to the origin of achoa including transposition of achoa and pcoma , origin from pcoma , origin from junction of ica and pcoma , and origin from middle cerebral artery4,5 ) .\nthe clinical findings of transposed achoa cases including present one are summarized in table 1 .\nall of the transpositions of achoa occurred in the left side . among all the cases ,\nour case showed sah due to ruptured aneurysm arising from fetal type of pcoma among multiple cerebral aneurysms founded and achoa originating from ica proximal to pcoma .\ntypically , achoa runs posteromedially within the crural cistern and continues ambient cistern to enter the choroidal fissure .\nthe proximal portion of this artery is cisternal segment and following portion becomes intraventricular segment1 ) .\nthe transposed achoa in the previous cases including ours did not seem to affect the vascular territory or course despite of unusual vascular arrangements .\nthe achoa can be exposed or manipulated in surgical approaches into the pathological lesions around temporal lobe or involving supraclinoid ica .\nalthough the achoa aneurysms accounting for 4% of all cerebral aneurysms are not so common , vascular injury of achoa with small caliber supplying the eloquent areas may be critical because of the possibility of significant morbidity and mortality . and\n, another caution is that achoa do not have significant collateral flows despite a potential anastomosis with posterior choroidal artery3 ) .\nwe tried to preserve pcoma itself and all perforating branches arising from it because of the possibility to compromise the collateral flows of fetal type pcoma .\nit is notable that careful review of the preoperative angiograms helps to find unexpected vascular anomalies which may impose an additional surgical risk .", "answer": "the anterior choroidal artery has several kinds of variations . among them , \n the transposition of anterior choroidal artery and posterior communicating artery origins has been extremely rare . \n we report a case with cerebral aneurysm arising from posterior communicating artery which origin was distal to the anterior choroidal artery and review the relevant literature .", "id": 658} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na pure ground - glass nodule ( ggn ) in the lung may represent an early lung malignancy , such as adenocarcinoma in situ ( ais ) or minimally invasive adenocarcinoma ( mia ) ( 1 ) .\napproximately 20 - 30% of patients with adenocarcinoma and a predominantly pure ggn who undergo surgery have additional ggn lesions , either in the same or different lung lobes ( 2 ) . in such cases , multiple limited resection may be an appropriate treatment if a few pure ggn lesions are scattered in multiple lobes or peripherally in one lobe , and the patient has sufficient pulmonary functional reserve ( 3 ) .\nhowever , alternative options should be considered if several ggn lesions are scattered in both lungs with multiple lobes involved , and there is a risk for insufficient pulmonary functional reserve after resection .\nchemotherapy has been suggested as an additional therapeutic option , if surgery is not possible due to a lack of pulmonary functional reserve ( 4 ) .\nanother strategy is to rely on serial computed tomography ( ct ) scans until the nodule develops a definite solid portion .\nif curative therapy is not performed , there remains a significant chance for progression ( 1 ) .\ncryoablation has been explored as an option for treating metastatic lesions in patients with non - small cell lung cancer who can not undergo surgery or chemotherapy ( 5 ) . however , no clinical reports of cryoablation techniques applied to multiple ggns in the lung have been published . here\n, we describe a patient with lung cancer and a pure ggn in the left lower lung lobe that persisted after several limited resections and was successfully treated with cryoablation .\na 59-year - old woman visited our hospital due to abnormal chest radiography findings on a health maintenance exam at another hospital .\nall pre- and post - procedural ct scans were performed using a multi - detector ct scanner ( somatom definition flash , enlargen siemens , forchheim , germany ) .\nthe scanning parameters were : 120 kvp , 200 mas , 0.75-mm collimation , 2-mm reconstruction intervals , smooth algorithm , and pitch of 1 .\nseveral ggns were detected by ct scan : a 12-mm - sized , partially solid nodule in the right middle lobe ( fig .\n1a ) , a 7-mm - sized pure ggn in the right upper lobe , and two 5-mm - sized pure ggns in each of the lower lobes ( fig .\nthe patient underwent a right middle lobectomy and wedge resection of the right upper lobe using video - assisted thoracoscopic surgery .\nthe partially solid nodule in the right middle lobe was diagnosed as adenocarcinoma , and the pure ggn in the right upper lobe was diagnosed as a mia .\nthe two pure ggns in both lower lobes remained without significant change on a 10-month follow - up ct scan .\nan additional wedge resection was performed for the pure ggn in the right lower lobe , and this nodule was diagnosed as ais .\nafter these surgeries , the patient did not have sufficient pulmonary functional reserve to tolerate any additional surgery .\nthus , we decided to perform cryoablation on the pure ggn in the left lower lobe .\nthe patient fasted for 6 hours before the procedure , and her blood coagulation parameters were checked .\nwe used an argon and helium gas - based system ( seednet , galil medical , yokneam , israel ) , a 1.5-mm 17-g cryoprobe , and a thermal sensor .\nthe procedure was performed in a fluoroscopy room by an interventional radiologist . after placing the patient in the prone position on the table ,\na cross - shaped radio - opaque skin marker was applied to determine the needle insertion site under fluoroscopy .\nsubsequently , a c - arm cone - beam ct ( cbct ) scan ( dynact , enlargen siemens ) was taken ( fig .\n1d - f ) to obtain 1.5-mm thick axial , coronal , and sagittal images . based on these images\n, we measured the distance from the center of the skin marker to the target ggn .\nthe area of the skin marker was draped , and a 1% lidocaine solution was injected into the skin down to the pleural surface . after localizing the needle tip , a cbct scan was performed to confirm the probe insertion site . a 17-g cryoprobe (\nseednet , galil medical ) was carefully introduced into the pure ggn under fluoroscopic guidance .\nwe used a fluoroscope and cbct to visualize the size of the ice ball during the procedure .\nwe took a ct scan to confirm that the ice ball had reached sufficient size , as indicated by a low attenuation region with an envelope of ground - glass opacity and a margin of 1 cm beyond the ggn .\na small pneumothorax was noted after removing the cryoprobe ; however , the patient was asymptomatic with stable vital signs .\nwe performed a follow - up ct scan 1 day after cryoablation to assess any initial changes in the ablated lesion and procedural - related side effects ( fig .\nthe scan showed a 3-cm sized ablated zone in the left lower lobe with no major procedure - related complications , such as hemothorax .\nthe size of the ablated zone had decreased markedly on a follow - up ct scan 2 months later .\nthe pure ggn in the left lower lobe was judged to have been successfully ablated without recurrence on a 6-month follow - up ct scan ( fig .\nour results show the potential of cryoablation as a new treatment method for ggn , particularly in patients in whom surgery is contraindicated .\nsome controversy exists as to whether some nodules should be resected or followed by serial ct scans .\nkim et al . ( 6 ) noted that several pure ggn lesions detected in patients undergoing surgery for bronchioloalveolar carcinoma did not change in size or features during follow - up .\nthey suggested that surgical resection should be considered in selected cases in which nodules exhibit significant changes in size or appearance during follow - up .\n( 7 ) found that all ggn lesions > 10 mm were carcinomas and insisted that these lesions should be resected rather than followed .\npartially solid ggn lesions should be resected regardless of size because they represent more invasive lesions than pure ggns .\nthus , a non - surgical alternative is needed for patients with insufficient pulmonary functional reserve or in patients in whom surgery is technically not feasible .\nminimally invasive ablation techniques , such as radiofrequency ablation ( rfa ) and cryoablation , may be useful adjunctive treatment options for lung cancer or metastatic lesions and preserve pulmonary function ( 5 , 9 , 10 ) .\nminimally invasive ablation techniques for lung cancer have several advantages , including selective damage , minimal morbidity and mortality , minimal loss of lung function , repeatability , low cost , excellent monitoring during treatment , less pain , and shorter hospital stay ( 11 ) . ablating lung tumors is currently used for curative treatment of primary lung cancer and metastatic lung malignancies or cytoreduction ( 12 ) .\nablation is also an option in patients with lung metastases from colorectal and renal cell carcinoma , melanoma , hepatocellular carcinoma , or primary sarcoma ( 13 ) .\nalthough rfa is a contemporary tumor ablation technique , it may cause serious complications , such as air embolism or uncontrolled pain ( 9 , 14 ) .\ncryoablation is a thermoablational technique that consists of alternating cycles of decreasing ( freezing ) and increasing ( thawing ) temperatures , leading to direct cellular and vascular injury .\ncryoablation works by forming an ice ball , which causes increased extracellular osmolarity and , as a consequence , water diffuses from the intracellular space into the extracellular space .\nthus , cryoablation may be a better option for patients with extensive emphysema ( 10 ) .\nhowever , percutaneous or surgical biopsy was difficult due to the small size and multiplicity of the ggn lesions .\nnevertheless , localized ggns can include invasive disease , such as ais or mia ( 1 ) . in our case ,\ntwo similar nodules in the right upper and right lower lobes were identified during surgery as mia and ais , respectively .\ncryoablation may reduce the likelihood that a remnant ggn will progress to advanced cancer and does not require additional surgery .\nthus , long - term follow - up may be necessary to determine the outcome of cryoablation for treating pure ggns . in conclusion", "answer": "treatments for pure ground - glass nodules ( ggns ) include limited resection ; however , surgery is not always possible in patients with limited pulmonary functional reserve . in such patients \n , cryoablation may be a suitable alternative to treat a pure ggn . here , we report our initial experience with cryoablation of a pure ggn that remained after repeated surgical resection in a patient with multiple ggns . \n a 5-mm - sized pure ggn in the left lower lobe was cryoablated successfully without recurrence at the 6-month follow - up .", "id": 659} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese \n materials are made of either latex ( natural rubber ) or synthetic polymer materials \n ( polyurethane ) .\nlatex elastics are more commonly used because they present improved \n properties such as : greater flexibility , lower cost and greater capacity of returning to \n the original dimensions after undergoing deformation . in orthodontic practice\n, the use of elastics has some advantages , such as \n biocompatibility , low cost , easy installation and removal by the patients .\nhowever , the oral environment may \n interfere negatively in the properties of these materials .\nexposure of these elastics to \n oral environment results is degradation of their elastic forces .\nliterature has reported \n that rubber elastics exposed to oral environment lose between 10 to 40% of their initial \n force .\nafter 1211 to 24 \n h of installation , this \n degradation rate is greatly reduced , resulting in forces with reasonably constant \n intensity . moreover , in spite of being considered a biocompatible material , santos , et \n al .\nthe elongation of the molecular chains of materials should be considered one of the main \n mechanisms by which the elastic force decay occurs . when the elastic stretches , the \n polymer chains are uncoiled becoming elongated .\nif the force is excessive , such chains \n will slide one over another resulting in permanent deformation of the material and \n consequently in the degradation of the force generated by the elastic .\nadditionally , the oral environment acts as an agent of the elastic force degradation \n because of physical damages , e.g. : mechanical traumas and temperature \n alterations .\nmoreover , the \n chemical interactions among the material , saliva and dietary substances promote both the \n absorption of water and other salivary constituents and the solubilization / release of \n the material 's components in the saliva , consequently modifying the elastics ' molecular \n structure and favoring their degradation .\nmost studies on the influence of the oral environment are conducted in \n vitro , evaluating humidity , saliva composition , ph , temperature and stress \n induced by elastic cyclic stretch .\nhowever , few studies on the effects of dietary \n substances are found in the literature .\n( 2004 ) evaluated the \n effect of diet on the mechanical properties of intermaxillary elastics .\nthese authors \n observed that dietary substances did not significantly increase the degradation of the \n mechanical properties of elastics .\n( 1998 ) verified that the immersion of elastomeric chains in \n coca - cola resulted in a greater degradation of forces compared with the \n immersion in water .\n( 2008 ) demonstrated that immersion in coca - cola was \n not able to alter the pattern of force degradation in two different types of elastomeric \n chains .\nintermaxillary elastics have been routinely employed in orthodontics it is thus \n important that orthodontists be aware of the mechanical properties of these materials as \n well as of the influence of oral environment factors on their properties . due to the \n limited number of studies evaluating the effect of diet on force degradation , the aim of \n this study was to evaluate in vitro the effects of frequently ingested \n beverages on the force degradation of intermaxillary elastics .\none hundred and eighty medium force 1/4-inch intermaxillary elastics ( tru - force latex \n elastic system ; tp orthodontics inc . ,\nla porte , in , usa ) were used and divided into six \n groups ( n=30 ) : group 1 ( control - artificial saliva ) , group 2 ( coca - cola - \n coca - cola company , so paulo , sp , brazil ) , group 3 ( beer - heineken , so paulo , sp , \n brazil ) , group 4 ( orange juice - del valle pure squeezed orange juice , coca - cola \n company , so paulo , sp , brazil ) , group 5 ( red wine - santa lucia cabernet sauvignon , \n henriquez hermanos ltd . ,\ntalca , chile ) , group 6 ( coffee - nescaf classic , nestl s.a . , \n araraquara , sp , brazil ) .\nthe composition of artificial saliva was 0.0625% kcl , 0.0865% \n nacl , 0.0056% mgcl2 , 0.0166% cacl2 , 0.0804% \n na2hpo4 , 0.0326% kh2po4 , 4.274% sorbitol , \n 0.0004% naf , 0.1% c6h5coona , 2% carboxymethylcellulose and \n distilled water .\nelastics with tensile strength ranging from 1.55 to 2 n were selected to standardize the \n samples and eliminate possible mechanical behavior bias .\ntherefore , 282 elastics were \n tested to reach a test sample size of 180 elastics .\ninitially all elastics were mounted on an epoxy resin board on two steel pins at a \n distance of 26 mm ( figures 1a and 1b ) and their \n forces were measured in a tensile testing machine ( dl1000 ; emic ltda . , so jos dos \n pinhais , pr , brazil ) at a crosshead speed of 150 mm / min .\nb ) \n elastic stretched at 26 mm next , the samples were randomly divided into six groups .\nthe test of variance \n homogeneity was applied to verify the baseline forces , showing statistically similar \n mean values of initial forces ( p>0.05 ) among the groups .\nafter the baseline readings , the elastics were immersed in a glass flask ( 15x9x14 cm ) \n containing 300 ml of the tested beverages , according to the experimental groups . \n\nimmersion period was 15 min for the first ( t1 ) and second ( t2 ) cycles and 30 min for \n third to fifth ( t3 , t4 , t5 ) cycles . at every immersion cycle ,\nthe beverages were changed \n ( figure 2 ) and the elastics were washed in \n distilled water and immersed into 300 ml of artificial saliva for 3 min .\nnext , the \n elastics were again washed in distilled water and removed from the resin board to \n perform a new tensile strength test .\nsequence of the experimental groups data were analyzed by one - way repeated measures anova to compare the effects of \n intervals , beverages and the interaction between them .\nfigure 3 shows the homogenous distribution of the \n sample at t0 , where the groups presented statistically similar mean values of initial \n force ( p>0.05 ) .\nsince the mean force values of each group were statistically similar , \n it may be affirmed that the alterations were due to the tested treatments and not to the \n differences in each group behavior .\nhomogeneous distribution of samples at t0 figure 4 exhibits the mean force values produced \n by the intermaxillary elastics regardless of their groups .\nnotice that in the first \n moments ( from t0 to t1 ) , there was a greater reduction of the generated forces \n ( p<0.05 ) , followed by a decrease of degradation rate in the following periods .\nmean force values of the intermaxillary elastics regardless of the group this same behavior pattern was seen in the tensile strength forces produced by each \n group at all observation periods ( figure 5 ) .\nfigure 5 reveals that the different groups behaved \n similarly at each study period ( t1 , t2 , t3 , t4 and t5 ) ( p>0.05 ) .\nthis study evaluated in vitro the effects of frequently ingested \n beverages on the force degradation of intermaxillary elastics .\nthe force degradation of \n intermaxillary elastics , measured by tensile strength test , was observed at all periods , \n regardless of the group ( figure 4 ) . the greatest \n degree of force degradation occurred at the initial periods ( from t0 to t1 ) and a \n gradual reduction of this degradation occurred at the following periods , showing a \n tendency to reduction over time .\nthis was confirmed by the statistically significant \n difference existing between t0 and t1 , t1 and t2 , t2 and t4 , t3 and t5 ( p<0.05 ) .\nthe mechanical behavior of intermaxillary elastics in the present study was similar to \n the findings of previous studies in which a greater degradation in the elastic forces at the initial \n periods of assessment was detected .\n( 2011 ) found a different behavior of the degradation of \n elastic forces : after a first phase of greater force degradation , there was a second \n stage where the elastics partially recovered the force ( negative degradation ) , followed \n by a third stage in which slow and gradual force degradation occurred . due to this behavior ,\nandreassen and bishara ( 1970 ) suggested the use of a force magnitude four times greater \n than the intended magnitude for a determined case .\nconsequently , when the elastics lose \n 40% of their initial force , levels close to those required would still be present for \n longer periods .\nnotwithstanding , \n such procedure should be carefully analyzed because of the risks of damaging the tooth \n and periodontal tissues by excessively strong forces .\nadditionally , the findings of an \n in vivo study \n suggested that elastics should be changed daily because the oral activity dynamics would \n increase the fatigue and deformation of material , enhancing the risk of their fracture \n and failure .\nsome in vitro studies have been conducted using a dynamic experimental \n model in which mouth opening and closing movements are simulated , stretching the \n intermaxillary elastics .\nfor the present study , a static experimental model was chosen \n based on the results of previous investigations , which demonstrated that \n the cyclic elastic stretching only enhances force degradation in the first hour of the \n experiment ; after this period , the degradation rate returns to its pattern and , by the \n end of the study , cyclic stretching or not exerts no statistically significant influence \n on the elastics . liu , et \n al .\n( 1993 ) showed that after \n 200 stretching cycles there was no significant force degradation of intermaxillary \n elastics .\nthe results of this research indicate that the contact of dietary beverages with \n intermaxillary elastics is not able to influence the degradation degree of their forces \n ( figure 5 ) .\nthe elastics presented the same \n behavior when immersed in either artificial saliva or test beverages at all \n observational periods .\nthe lack of influence of dietary components on the degradation of \n intermaxillary forces has also been observed in a laboratory study .\nother studies have \n demonstrated that the ph of the medium in which the intermaxillary elastics are immersed \n did not influence significantly force decrease of the elastics .\nbased on this evidence , \n the beverages used in the present study were not subjected to any ph analysis .\nthe mechanical behavior of the intermaxillary elastics in the present study can be \n explained by the \" swelling phenomenon \" .\nthe chemically cross - linked points among the \n molecular chains enable the absorption of liquid into the latex three - dimensional \n reticulate structure .\nthe rubber 's free energy decreases with the simultaneous effect of \n mixing entropy . at the same time\n, the molecular chains are elongated followed by the \n decrease of elasticity of the rubber .\nalthough this study showed solid evidences , the obtained results should be carefully \n examined because no in vitro study is capable of simulating all factors \n acting on intermaxillary elastics in the oral environment .\nnotwithstanding , our findings \n contribute to improve the knowledge of the mechanical behavior of the intermaxillary \n elastics employed in orthodontics , enabling greater predictability in the application of \n mechanotherapy involving latex elastics .\nthe results also have clinical applications \n since no restrictions were found to the consumption of the studied beverages in relation \n to the use of the tested intermaxillary elastics , bringing comfort and freedom for \n patients choosing their own diet during the orthodontic treatment .\nthe chemical nature of the evaluated beverages was not able of influencing the degree of \n degradation of intermaxillary elastics ' forces .", "answer": "objective : the aim of this study was to evaluate in vitro the effects of \n frequently ingested beverages on force degradation of intermaxillary elastics . \n \n material and methods : one hundred and eighty 1/4-inch intermaxillary elastics ( tp orthodontics ) were \n immersed into six different beverages : ( 1 ) coca - cola ; ( 2 ) beer ; ( 3 ) \n orange juice ; ( 4 ) red wine ; ( 5 ) coffee and ( 6 ) artificial saliva ( control ) . \n the \n period of immersion was 15 min for the first and second cycles and 30 min for the \n third to fifth cycles . \n tensile forces were read in a tensile testing machine \n before and after the five immersion cycles . \n one - way repeated measures anova was \n used to identify significant differences . \n results : force degradation was seen in all evaluated groups and at all observation periods \n ( p<0.05 ) \n . a greater degree of degradation was present at the initial periods , \n decreasing gradually over time . \n however , no statistically significant differences \n were seen among groups at the same periods , showing that different groups behaved \n similarly . \n conclusion : the chemical nature of the evaluated beverages was not able to influence the \n degree of force degradation at all observation periods .", "id": 660} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute promyelocytic leukemia ( apl ) is one of the most characteristic subtypes of aml in which abnormal promyelocytes predominate within peripheral blood or bone marrow .\nalso , t(15;17)(q22;q21 ) shows a characteristic chromosomal translocation in apl , observable in 70 - 90% of apl patients .\nowing to all trans - retinoic acid ( atra ) combined with chemotherapy , apl has one of the highest cure rates of all types of aml .\nseventy to eighty percent of newly diagnosed apl patients with the pml - rara rearrangement are cured or under long - term remission , yet some of them have a poor prognosis [ 2 - 5 ] . because cytogenetics is one of the most powerful prognostic factors for the outcome of aml , cytogenetic abnormalities can cause change in treatment response , relapse , and clinicopathological characteristics .\nincidence of secondary cytogenetic abnormalities has been observed in ~40% of apl cases , but their prognostic significance is still unclear [ 5 - 7 ] .\nabout 1% of the reported secondary cytogenetic abnormalities in apl patients are ider(17)(q10)t(15;17)(q22;q12 ) , an infrequent type of additional recurrent chromosomal abnormality , according to a recent study . however , ider(17)(q10)t(15;17 ) associated with the pml - rara rearrangement in microgranular variant apl is even more rare . as far as we know ,\nonly 2 cases of the ider(17)(q10)t(15;17 ) abnormality in microgranular apl have been previously reported [ 8 , 9 ] . here\n, we describe an unusual microgranular apl case associated with ider(17)(q10)t(15;17 ) , identified by both conventional cytogenetics and fish analyses at the initial diagnosis .\na 59-yr - old woman who had previously been diagnosed with cerebral infarction was brought to our hospital due to right side weakness in november 2007 .\nthe initial complete blood count showed pancytopenia , hb level of 9.9 g / dl ( reference range 12 - 16 g / dl ) , platelet count of 83,000/l ( reference range 150,000 - 350,000/l ) , and white blood cell count of 1,000/l ( reference range 4,000 - 10,000/l ) .\nbone marrow aspiration showed a hypercellular marrow replaced by increased promyelocytes with a paucity or absence of granules , accounting for 36% of all nucleated cells ( fig .\nthe results of special staining of bone marrow specimens were as follows : myeloperoxidase , positive ; periodic acid schiff , negative ; nonspecific esterase , negative .\nflow cytometric analysis was conducted and showed that the blasts were positive for cd13 ( 91.1% ) , cd33 ( 83.9% ) , cd117 ( 59.2% ) , cd2 ( 43.9% ) , and cd45 ( 25.4% ) , and negative for hla - dr ( 3.4% ) , cd3 ( 1.3% ) , cd7 ( 0.6% ) , cd10 ( 1.8% ) , cd14 ( 2.4% ) , cd19 ( 5.1% ) , cd34 ( 1.4% ) , cd41 ( 2.9% ) , cd56 ( 1.2% ) , and tdt ( 0.9% ) .\nfish signals from pml - rara probes ( abbott molecular / vysis , des plaines , il , usa ) yielded the results of nuc ish(pml , rara)4(rara con pml3)[24/138 ] , ( pml , rara)6(rara con pml5)[14/138 ] , ( pml , rara)3(rara con pml2)[13/138 ] , consistent with the abnormal fusion signal patterns seen in 37% of the nuclei examined ( fig .\nthe patient was diagnosed with apl and treated with induction chemotherapy consisting of daunorubicin , cytosine arabinoside , and atra . after completing induction chemotherapy ,\nfollow up bone marrow examination in january 2008 showed no evidence of morphologically visible residual leukemia .\nthe concurrent karyotype analysis result was 46,xx in all analyzed cells ; and pml - rara fish showed \" nuc ish ( pml , rara)2 \" in which the abnormal signal pattern was not observed .\nthere was no evidence of a pml - rara fusion gene in the reverse transcriptase - pcr ( rt - pcr ) analysis .\nas indicated by follow - up bone marrow biopsies conducted until september 2008 , the patient remained in complete remission . during this period\n, the rt - pcr analysis did not show any signs of the pml - rara fusion gene while other cytogenetic studies also indicated normal findings .\napl is a distinct subtype of aml and constitutes about 5 - 8% of all cases of aml diagnosis . according to the 2008 who classification\n, apl can be diagnosed when there is a t(15;17 ) or a pml - rara rearrangement , even if peripheral blood or bone marrow studies show less than 20% promyelocytes . as recently reported by manola et al . and\nour study group , the ider(17)(q10)t(15;17 ) , an isochromosomal abnormality that occurs on the long arm of ider(17)t(15;17 ) after reciprocal translocation of t(15;17 ) , is a relatively rare type of an additional recurrent cytogenetic abnormality that has been reported in 62 apl patients worldwide [ 8 - 13 ] . according to these studies , the influence of ider(17)(q10)t(15 ; 17 ) on the prognosis of adult apl patients\nindeed , 4 previously reported apl cases in children were all related to poor prognosis [ 8 , 13 - 15 ] , inferring that a more close and careful interpretation is necessary for childhood apl cases .\nwhat is interesting is that so far , reports of ider(17)(q10)t(15;17 ) from microgranular variant ( aml - m3v ) type are extremely rare .\nout of 62 total cases , information on apl morphology type were available in 42 cases , and most of these cases ( 40/42 ) were of the hypergranular apl type , except for 2 cases that clearly indicated aml - m3v ( table 1 ) [ 8 , 9 ] .\ntherefore , further research is required to determine whether ider(17)(q10 ) and aml - m3v have a low association , and more careful observation should be conducted to prevent underestimating aml - m3v patients among ider(17)(q10)t(15;17 ) cases .\nfurthermore , double ider(17 ) ( q10)t(15;17 ) is so rare in the international public databases that only 2 cases of apl patients indicating double ider(17)(q10)t(15;17 ) chromosomal abnormalities have been reported ( table 2 ) [ 16 , 17 ] . in double ider(17)(q10)t(15;17 ) , a gene dosage effect is observed owing to chromosomal abnormalities such as the pml - rara fusion gene on chromosome 17 or the quadruplication of der(17q ) . in addition , since the deletion of the tumor suppressor gene tp53 occurs by the loss of 17p , further research is necessary to resolve the adverse prognosis of the apl group related to such copy number variations .\nowing to the limited amount of clinical data in the literature , the relatedness between double ider(17)(q10)t(15;17 ) and an adverse prognosis is still unclear [ 16 , 17 ] . in the case of our patient\n, it was hard to determine a strong association between the additional genetic aberration and prognosis because of the small clonal size of the \" double ider(17)(q10)t(15;17 ) \" abnormality .\nnevertheless , at least from a diagnostic perspective and as indicated in the authors ' recent studies [ 13 , 18 ] , minimal residual disease detection using such multiple abnormal fusion signals through the pml - rara fish analysis in apl patients associated with ider(17)(q10)t(15;17 ) or double ider(17)(q10)t(15;17 ) would be considered to be a useful follow - up marker in clinical laboratories or hospitals .\nadditional study would contribute toward a better understanding of the influence of ider(17)(q10)t(15;17 ) on the prognosis , survival , and treatment response of such apl cases in adults or children . to the best of our knowledge\n, however , this is the third case report of microgranular variant apl associated with ider(17)(q10)t(15;17 ) .", "answer": "we present a rare case of microgranular variant acute promyelocytic leukemia ( apl ) associated with ider(17)(q10)t(15;17)(q22;q12 ) of an old - age patient . \n the initial chromosome study showed a 46,xx , del(6)(?q21q25),der(15)t(15;17)(q22;q12),ider(17)(q10)t(15;17)[10]/47,sl,+ider(17)(q10)t(15;17)[3]/46,xx[16 ] . \n fish signals from a dual color dual fusion translocation pml - rara probe were consistent with the results of conventional cytogenetics . \n because of the rarity of ider(17)(q10)t(15;17 ) in microgranular apl , further studies on both gene dosage effect of this chromosomal abnormality and the influence of ider(17)(q10)t(15;17 ) on clinical features such as prognosis , survival , and treatment response of apl cases are recommended .", "id": 661} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe use of medical devices for temporary use or implantation in the blood circulation has resulted in an increased demand for evaluation of complications brought about by these devices .\nthis resulted also in - better defined iso requirements for testing one important and relevant aspect of testing of medical devices is the condition of blood exposed to the device .\nanticoagulation and flow conditions must be as similar as possible as in the clinical setting in order to achieve relevant test results .\nfor some devices , including grafts , stents , and catheters , this implies similar anticoagulation treatment as used in clinical situations , but also high flow through or around the device to obtain relevant shear stress conditions [ 2 , 3 ] .\nhowever , in some reports , blood was treated with other anticoagulants than in clinical situations .\nanimal models should be avoided if equally quality results may be obtained in other ways . in addition\n, animal blood has essential differences compared with human blood , particularly with regard to clotting and platelet function .\ntwo types of in vitro flow models ( often with human blood ) have been used extensively : the modified chandler loop and the roller pump closed - loop system .\nthe modified chandler loop consists of closed tubing partly filled with air . on rotation , devices in the tubing\nuse of this system may induce artefacts due to major forces applied to blood elements and protein denaturation at the air - liquid interface [ 911 ] .\nthis model appeared effective for short circulation times [ 1214 ] , but intrinsic blood damage reduces sensitivity and does not allow prolonged exposure to blood . to overcome the disadvantages of these models , the hemobile was constructed .\nin addition , the tubing contains no air , and there is no mechanical device compressing the tubing . in this way it was attempted to reduce damage and activation and to simulate pulsatile flow in a frequency similar to the arterial circulation .\nthe hemobile model was compared with the chandler loop and roller pump model for intrinsic damage to blood components and activation of platelets .\nthe hemobile was further used in testing tubular structures made of various polymers to show its effectiveness in determination of hemocompatibility by means of in vitro circulation of human blood .\nfresh human blood was obtained by vena puncture with a 19 gauge needle under low pressure from five healthy adult volunteers and anticoagulated with a clinical dose of heparin ( 1.5 iu / ml ) ( leo pharmaceutical products bv , weesp , the netherlands ) . before starting the experiment , cell count ( cell counter medonic ca 530 , medonic , sweden ) and platelet function analysis ( platelet function analyzer-100 )\nwere performed and platelet aggregation was determined by adding 50 mmol adp to a mixture of 500 l of blood and 500 l of saline and with the use of a whole blood aggregometer ( chrono log corp .\naggregometer , kordia life sciences , leiden , the netherlands ) to confirm proper blood quality relevant for this study and to provide baseline characteristics .\nthree circulation models were compared ; the modified chandler loop , roller pump , and hemobile model ( figure 1 ) .\nthe principle of the modified chandler model is based on a chamber of air that remains on top of a vertical rotating circular loop ( de spatel bv , roden , the netherlands ) .\nthe roller pump is a nonocclusive pump for clinical use in extracorporeal circuits ( stckert , munich , germany ) .\nthe hemobile ( haemoscan bv , groningen , the netherlands ) consists of a cylinder , which is forced in a semirotating movement . on this cylinder the circular loop circuits can be positioned .\ndue to the semirotating movement and the slowness of blood , a pulsating movement of blood through the circuits is generated which mimics pulsatile flow .\na ball valve ensures a directed flow of up to 40 ml / min through 3 mm tubing at 60 beats / min , thus creating shear stresses of 12 dynes / cm .\nalso , the flow wave form generated by the model is more physiological compared to the roller pump and chandler model .\na comparative study was performed to assess intrinsic blood damage for three different closed - loop circulation models , without any test device in the circuit .\neach set of experiments ( three different circuits in triplicate ) was performed five times with fresh venous blood from a different donor for each set . due to restrictions of the chandler loop model , the flow through 3 mm tubing\nwas limited to 25 ml / min ( 6 dynes / cm ) in all experiments .\nthe first set of experiments was performed under circumstances of similar flow ( 25 ml / min ) in all three test systems . \nthe following sets of experiments ( n = 4 ) were performed with the roller pump and hemobile at an exceeded blood flow of 40 ml / min ( 12 dynes / cm ) , which resembles shear stresses in the coronary blood circulation . \nafter these validation experiments , the hemobile was used to test the hemocompatibility of woven tubular structures from polyester ( pet ) fiber and dyneema purity uhmwpe fiber , in comparison with expanded polytetrafluoroethylene ( eptfe ) tubes .\nall experiments were performed with closed pvc tubing circuits ( raumedic ) with a length of 45 cm and an internal diameter of 3 mm .\nthe hemobile circuits were fitted with a ball valve connector ( halkey - roberts , street petersburg , fl , usa ) .\nthe roller pump circuit was partially immersed in water , whereas the chandler loop and hemobile were completely placed in an oven ( figure 1 ) .\nthe circuits of the roller pump and hemobile were filled with 4.5 ml of blood and the circuits rotating on the chandler loop system with 4.0 ml of blood and 0.5 ml of air .\ncell count , platelet function analysis , and platelet aggregation measurements were performed on the circulated blood , as described above .\nthe rest of the blood was mixed with 0.2 m edta and centrifuged at 11,000 g for one minute .\nplasma was used for analysis of thromboxane b2 ( txb2 ) , thrombin - antithrombin iii ( tat ) complexes , elastase , and hemoglobin concentrations .\nactivation of the arachidonic acid pathway in platelets results in the release of the potent platelet aggregating agent thromboxane a2 , which is rapidly converted to the inactive product txb2 .\ntxb2 was measured by means of an enzyme immunoassay ( biotrak , amersham , uk ) , based on competition of labelled txb2 with sample txb2 . in this test\nthe label is a peroxidase , which converts the substrate tetramethylbenzidine , yielding a yellow colour which is measured at 450 nm by a spectrophotometer ( powerwave 200 , biotek instruments , winooski , vt , usa ) .\nthrombin formation during the in vitro experiments was determined by means of tat complexes in edta plasma .\na tat elisa was performed with capture and detection of antibodies from cederlane laboratories ( hornby , canada ) .\nrelease of polymorphonuclear ( pmn ) elastase in vivo is a specific marker for inflammation reactions .\nfree in plasma , elastase is rapidly neutralised by 1-antitrypsin inhibitor to form a stable complex .\nelastase was determined by elisa by means of capture antibody against human elastase and labelled detection antibody against alpha1 antitrypsin ( affinity biologicals , ontario , canada ) .\ncomplement activation was determined by elisa based on a mouse anti human c5 - 9 antibody ( dako , glostrup , denmark ) and goat anti - c5 detection antibody ( quidel , san diego , ca , usa ) .\nfree hemoglobin as an index for erythrocyte damage was measured as described by harboe and using a spectrophotometer ( power wave 200 ) .\nthe emptied pvc circuits and the incubated graft material were washed with tris - buffered saline ( ph 7.4 ) .\nplatelet adhesion onto the surface of the circuits was measured by means of a colorimetric assay , based on the presence of acid phosphatase in platelets .\nplatelet binding was measured based on the release of platelet acid phosphatase in citrate buffer ( ph 5.4 ) , containing p - nitrophenyl phosphatase and triton x100 .\nsubstrate conversion is proportional to the amount of platelets , which was determined by a standard curve and platelet counting .\nscanning electron microscopy ( sem ) was achieved on material fixated in 2% glutaraldehyde in cacodylate buffer , treated with osmium tetraoxide in cacodylate buffer and gold sputtered critical point dried samples .\nthese were visualized at 2 kv ( jeol 6301 f , jeol ltd . ,\nanova was performed for all blood parameters to assess any difference in blood cell damage or activation between the circuits .\nplatelet - count was significantly reduced by the roller pump and by the modified chandler loop , but not by the hemobile ( figure 2 ) .\nplatelet function was partially decreased in all systems , in particular in the roller pump system .\nplatelet adhesion to the pvc tubing was lowest in the chandler loop ( table 1 ) .\ntxb2 and free hemoglobin were significantly higher after roller pump circulation than after chandler loop and hemobile circulation ( table 1 ) .\npump and hemobile could be applied at a flow of 40 ml / min , which was not possible with the chandler model .\nplatelet number remained higher , and hemolysis was lower in the hemobile circuits ( table 2 ) .\nplatelet count was reduced in the circuits containing a test chamber with eptfe , pet , or dyneema purity uhmwpe fiber by approximately 30% following circulation compared to baseline .\nplatelet function was reduced in all circuits to a similar extent ( figure 3 ) .\nplatelet binding based on the adhesion of antibody against the platelet gpiib receptor showed increased values on pet , whereas dyneema purity uhmwpe fiber had lowest gpiib receptors ( figure 4 ) . in the eptfe circuits ,\nrelease of txb2 and tat was lowest , whereas elastase , complement activation , and hemolysis were lowest in dyneema purity uhmwpe fiber circuits ( table 3 ) . \nmore detailed pictures showed platelets and fibrin usually separate and not as a dense thrombus on the surface .\ndifferences between the 3 types of graft materials were not clear from these pictures , although eptfe seemed to remain more devoid of deposition than pet and dyneema purity uhmwpe fiber ( figure 5 ) .\ninitial experimental blood circulation models with a roller pump , already refined in previous studies [ 13 , 14 , 18 ] , appeared efficient , reliable , and cost - effective to assess the haemocompatibility of grafts before their clinical use .\nhowever , blood damage induced by the pump caused a limitation of the exposure of the test object to circulating blood .\nthe modified chandler loop model is currently most frequently used for these purposes [ 19 , 20 ] .\nfirst , the continuous blood - air contact induces leukocyte and platelet aggregation , protein denaturation [ 911 ] , and shear forces on particulate material , which can result in detachment [ 21 , 22 ] . in our experiments , indeed less platelets were observed on tubing exposed to blood - air contact in the chandler loop than in the roller pump or hemobile circuit .\nthe second disadvantage of the chandler loop is the limitation of blood circulation due to the requirement to keep the air on top of the circuit .\nthus , our 3 mm tubing did not allow a blood flow over 25 ml / min , which is half of the arterial flow in the coronary system . at a flow of 25 and 40 ml / min ,\nthe hemobile could be used and was less traumatic for blood than the roller pump model .\nit is well known that any type of foreign body material can be thrombogenic by promoting the formation of thrombin and platelet activation , which facilitates platelets to adhere and to express surface receptors ( gp iibiiia ) of activated phase .\nplatelet binding becomes then irreversible and can promote more thrombus formation . therefore , proper testing of the characteristics of graft material is an important issue in modulating blood interaction .\nthe small tubular system used in the present models allows multiple tests with fresh human blood .\nthe modified chandler loop and hemobile can be easily loaded with a number of circuits at a time . fast screening of thrombogenicity of vascular grafts and other small medical devices is possible .\nthe adjustable flow and shear and the pulsatility in the hemobile renders it in a model that allows standardised testing of these devices at the cost of low intrinsic blood damage , while closely mimicking the in vivo conditions .\nour results indicated that the changes in circulating blood are most of all dependent on the material used in the test loop . moreover\na direct comparison of material surfaces was possible by using blood of the same donor for different circuits .\nthe feasibility of the hemobile has been demonstrated by applying the model in hemocompatibility studies of different vascular graft materials . \nwoven tubes made of pet fiber and dyneema purity uhmwpe fiber have been compared to commercially available eptfe vascular graft .\nour results showed that dyneema purity uhmwpe fiber has in many ways better properties than eptfe by lower activation of the inflammatory response and lower hemolysis .\na limitation of in vitro models is mainly represented by the absence of an endothelial layer in the circulating system . throughout the release of cytokines , the endothelium has a major role in mediating the interplay between the injured vessel wall and circulating blood cells [ 2426 ] .\nthis is effectuated by the release of cytokines and ( anti)thrombotic components as well as the expression of adhesion molecules .\nprior to use in patients an animal model should prove the validity of the in vitro data .\nnevertheless , all the other elements depicting the blood - graft phase boundary scene are present , while the use of human blood from one donor in test and control circuits is a major advantage for comparison of the materials .", "answer": "three different models , a modified chandler loop , roller pump , and a new ball valve model ( hemobile ) , were compared with regard to intrinsic damage of blood components and activation of platelets . \n the hemobile was used for testing of polymer tubes . \n \n high flow was not possible with the chandler loop . \n the roller pump and the hemobile could be adjusted to high flow , but he pump induced hemolysis . \n platelet numbers were reduced in the roller pump and chandler loop ( p < 0.05 ) , but remained high in the hemobile . \n platelet aggregation was reduced in all models . \n \n the hemobile was applied for testing vascular graft materials , and allowed different circuits circulated simultaneously at 37c . \n eptfe , dyneema purity uhmwpe fiber and pet fiber based tubes , all showed hemolysis below 0.2% and reduced platelet count and function . \n binding of fibrin and platelets was higer on pet , inflammatory markers were lowest on dyneema purity uhmwpe . \n \n we concluded that the hemobile minimally affects blood and could be adjusted to high blood flows , simulating arterial shear stress . \n the hemobile was used to measure hemocompatibility of graft material and showed dyneema purity uhmwpe fiber in many ways more hemocompatible than eptfe and pet .", "id": 662} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nboth tues and rcn - ube support the community to catalyze change within undergraduate biology education and , in effect , act synergistically .\ntues supports change in the way courses are taught , development of new materials ( including new assessment materials to support these approaches ) , and research into undergraduate education in general .\ntues funds can be used to support course development by funding faculty time and other resources , including some funds for initial purchase of instrumentation essential to the development and implementation of transformative changes in student laboratories and/or lecture classes .\ntues funds also may be used for faculty development activities that prepare other faculty to incorporate these new ideas into their own teaching ( nsf , 2006 ) .\ntues also supports evaluation , webinars , conferences , and a project information portal ( american association for the advancement of science [ aaas ] , 2011 ) .\nthe current ( fy2013 ) program has tracks ranging from small pilot projects with funding caps of $ 200,000 to large national projects with funding caps of $ 6 million .\nthe rcn - ube program focuses on forming alliances of faculty , professional societies , and institutions active in developing , among other things , learning in emerging technologies in the biology curriculum , strategies and approaches for engaging biology faculty in professional development , incorporating emerging subdisciplines into the biology curriculum , improving assessment of student learning , improving the transition of students from 2-yr to 4-yr institutions , and incorporating authentic research experience into undergraduate laboratory courses ( nsf , 2012b ) .\nthe coordination efforts may include holding workshops , generating websites , or other appropriate means of developing a community of practice .\nthe rcn - ube program has two tracks , a full proposal track that funds projects up to $ 500,000 and an incubator track that funds projects up to $ 50,000 .\nthe incubator track accepts proposals that request support for the initial development of networks that will catalyze positive changes in biology undergraduate education . about a half - dozen incubator awards\nwhile the number of proposals submitted to the program has declined , the funding rates have remained high ( table 1 ) .\n( the average funding rate across the 5 yr of the program is 41.8% ; this is nearly double the average nsf funding rate [ nsf , 2012a ] . )\nyearly distribution of proposals and awards within the rcn - ube program data from nsf report server .\nwww.nsf.gov / awardsearch/. a glance at the recently funded projects within these programs ( see the supplemental material ) should help the reader understand the scope of these two programs and how they relate to one another .\nprincipal investigators do not need to have an ongoing project in one program in order to apply to the other , but may apply to both programs , as appropriate .\ntues serves all science , technology , engineering , and mathematics ( stem ) disciplines , as well as projects that involve interdisciplinary approaches , research on undergraduate stem education , assessment of student learning , and evaluation of teaching approaches .\nbiology proposals are handled by one of the nine teams ( biology , chemistry , computer science , engineering , geology , mathematics , physics , interdisciplinary , and research and assessment ) within the program . in 2012 ,\n1007 proposals were submitted to the program . of these , only 97 ( 10% ) focused on biology education ( table 2 ) .\ntable 2 also shows that 41% of all stem graduates in the united states are biology majors , and 22% of all u.s .\nif we compare these data with the results for engineering , which has 24% of all stem graduates each year and 14% of the stem faculty , we see a great disparity in the degree to which faculty in these two disciplines seek funding for instructional changes in their classrooms .\nfully 28% of the tues proposals submitted in 2012 were submitted by engineering faculty , while only 10% were submitted by biology faculty .\ndistribution of tues type 1 proposals submitted during fy 2012 and the number of majors and faculty members in the united states in the stem disciplines data from nsf report server .\nwe chose to compare engineering and biology undergraduate education because both are undergoing major reorganization ; engineering due to the pressures from the accreditation board for engineering and technology , and biology due to the pressures of the association of american medical colleges / howard hughes medical institute report scientific foundations for future physicians ( aamc / hhmi , 2009 ) , as well as the vision and change initiative ( aaas , 2011 ) .\nthe reasons for these strikingly disproportionate proposal submissions , despite similar demands for change in engineering and biology , are not apparent .\nit is our hope that articles such as this , along with frequent presentations by nsf staff at professional societies annual and regional meetings , will encourage the community of life sciences faculty to seek funding from this versatile program , which encourages a range of projects from small pilots to test new ideas through large multi - institutional collaborations designed to disseminate effective practices more broadly ( singer et al . , 2012 ) .\nbecause rcn - ube is a relatively new program , its impact on undergraduate biology education is only beginning to emerge . designed specifically to develop communities of people who are working on similar projects , but who otherwise may be unaware of others with similar interests , it generated a flurry of proposals in the first 3 yr , but this was followed by a dramatic decrease in the number of submissions .\nwe are hopeful that the increase in the number of proposals between 2011 and 2012 represents an appreciation of the value of this program to build and strengthen current or future collaborative efforts , as well as an awareness of the program within the community .\nit is certainly a program that can serve a crucial role in the development and dissemination of ideas generated to support the vision and change initiative call for action .\nthe number of proposals funded within any program depends not only on the number of proposals submitted but also on the quality of the proposals received .\nwriting a proposal for an educational initiative is essentially the same as writing a research proposal .\nit is important to : \n be sure the proposal is being submitted to the appropriate program;clarify the subject matter to be addressed in the instructional materials or practices;establish the evidence for the effectiveness of the instructional practices that the project builds on and intends to adds to;describe outcomes from any preliminary work you have done to test the potential of the approach;present implementation plans succinctly , so panelists can easily understand them and judge their potential for success;state the outcomes expected and how they will be determined and documented ; andindicate the level of support and/or interest either by colleagues within the department or elsewhere .\nbe sure the proposal is being submitted to the appropriate program ; clarify the subject matter to be addressed in the instructional materials or practices ; establish the evidence for the effectiveness of the instructional practices that the project builds on and intends to adds to ; describe outcomes from any preliminary work you have done to test the potential of the approach ; present implementation plans succinctly , so panelists can easily understand them and judge their potential for success ; state the outcomes expected and how they will be determined and documented ; and indicate the level of support and/or interest either by colleagues within the department or elsewhere .\nfor example , to determine whether the project is appropriate for a particular program , read the program solicitation carefully ; program officers are always available via email or telephone to answer specific questions .\nthe program solicitation provides the names of program officers associated with the program , as well as links to recent awards .\nthe evidence base for instructional best practices can be found in journals such as this one , as well as in publications such as vision and change in undergraduate biology education : a call to action ( aaas , 2011 ) and discipline - based education research : understanding and improving learning in undergraduate science and engineering ( singer et al . , 2012 ) .\nthis literature provides information on instructional best practices that inform the project being proposed and ground it in that research base .\nin addition to the tues and rcn - ube programs within nsf , there are a variety of other funding opportunities for faculty and students in the life sciences , including the following : \n the hhmi science education alliance helps \nbring good ideas in science education to a broader audience by offering educators models of research - based curricula developed to engage college students in true scientific discovery as early as possible in their academic careers \n( www.hhmi.org/grants/sea/index.html).the nih has internship , scholarship , and fellowship programs for undergraduates ( www.training.nih.gov/programs).the nih institutional research and academic career development awards help postdoctoral students develop teaching skills and pedagogical knowledge as they work with established faculty in minority - serving institutions , with the aim of facilitating the progress of postdoctoral candidates toward research and teaching careers in academia ( http://grants.nih.gov/grants/guide/pa-files/par-12-245.html).the u.s .\ndepartment of agriculture ( usda ) offers different pathway opportunities for students and recent graduates to work in agriculture , science , technology , math , environmental , management , business , and many other fields .\nthe usda offers internships to students and recent graduates to help them to excel in their chosen fields ( www.dm.usda.gov/employ/student/index.htm ) .\nbring good ideas in science education to a broader audience by offering educators models of research - based curricula developed to engage college students in true scientific discovery as early as possible in their academic careers \nthe nih has internship , scholarship , and fellowship programs for undergraduates ( www.training.nih.gov/programs ) .\nthe nih institutional research and academic career development awards help postdoctoral students develop teaching skills and pedagogical knowledge as they work with established faculty in minority - serving institutions , with the aim of facilitating the progress of postdoctoral candidates toward research and teaching careers in academia ( http://grants.nih.gov/grants/guide/pa-files/par-12-245.html ) . the u.s .\ndepartment of agriculture ( usda ) offers different pathway opportunities for students and recent graduates to work in agriculture , science , technology , math , environmental , management , business , and many other fields .\nthe usda offers internships to students and recent graduates to help them to excel in their chosen fields ( www.dm.usda.gov/employ/student/index.htm ) .\nthe biology staff of the division of undergraduate education has compiled a resource for those seeking information on the nsf programs that support improvement of undergraduate education in biology .\nthis document includes helpful information on proposal preparation , insights into the review process , and post - award management .\nwhile the information is useful for faculty in any discipline , the examples and advice given are oriented to the needs of biologists .\nthe document is updated in august of each year and can be obtained electronically by contacting helen vasaly ( hvasaly@nsf.gov ) .\nthe program officers and staff members at the nsf are looking forward to receiving your tues and rcn - ube proposals .", "answer": "many life sciences faculty and administrators are unaware of existing funding programs and of the strategies needed for writing an educationally related proposal . \n we hope to remedy this problem by making the life sciences audience aware of two national science foundation programs underutilized by the biology community .", "id": 663} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhailey - hailey disease ( hhd ) or familial benign chronic pemphigus first described in 1939 , is a rare autosomal dominant genodermatosis , which presents with recurrent vesicles , erythematous crusts and erosions in the areas subjected to friction , including , the neck and intertriginous areas .\nabnormalities in the tonofilament desmosome keratin complex results in marked acantholysis , giving the histological appearance of a dilapidated brick wall , which is pathognomonic of the disease . ultra violet b rays\nthe treatment is often not satisfactory and hence , various modalities of treatment have been tried .\nwe describe a case of hhd with a positive family history , in which various treatment modalities were tried without any benefit but responded well to thalidomide .\na 30-year - old unmarried male presented with a history of recurrent painful fluid and pus filled lesions followed by painful erosions over the neck , axillae , trunk and groins of 15 years duration exacerbated over the past 10 - 15 days .\nhe gave family history of similar disease in his father , paternal grandmother and paternal uncles . before coming to us ,\nhe had been treated with dapsone following which he developed agranulocytosis and dapsone was discontinued .\nseveral other treatment modalities including oral and topical antibiotics , corticosteroids were tried but resulted in only partial or temporary improvement .\nlarge macerated plaques studded with foul - smelling pus along with erosions , fissures , and crusts were present on the anterior and the lateral aspect of the neck , axillae , back , lower abdomen , pubic area , gluteal cleft , groins , upper medial thighs and scrotum [ figure 1 ] .\nerosions and crusts were seen on the glans with purulent foul smelling discharge in the prepucial sac , sparing rest of the penis .\nthe skin biopsy specimen for histopathological reconfirmation of the diagnosis revealed focal suprabasilar clefting , few acantholytic cells , intercellular edema with dilapidated brick wall appearance which confirmed our diagnosis [ figures 2 and 3 ] . macerated plaques with erosions and crusts over the scrotum , glans penis and upper medial thighs focal suprabasal clefting and lacunae ( h and e , 10 ) suprabasalar clefting with few acantholytic cells , intercellular edema and dilapidated brick wall appearance ( h and e , 40 ) patient was started on intravenous ( iv ) betamethasone 4 mg , 8 h which was tapered off with the introduction of 40 mg of oral prednisolone , iv ceftriaxone 1 mg twice daily and later iv piperacillin - tazobactam based on pus culture and sensitivity reports along with a combination of fusidic acid and betamethasone for topical application .\nhe continued to develop new lesions with the deterioration of his general condition and was febrile throughout . in spite of controlling the secondary infection , the vesicular eruptions persisted .\ntherefore , he was started on oral thalidomide 100 mg three times a day and a combination of betamethasone and gentamycin for topical application .\nmarked improvement was seen within a week of starting thalidomide [ figure 4 ] and hence we discontinued corticosteroid after rapid tapering of its dose and continued treating him with oral thalidomide 100 mg three times a day for one more week , which was then tapered off in 3 - 4 weeks and maintained on 50 mg daily .\nafter 6 months of receiving 50 mg thalidomide , the drug was stopped in view of no recurrence of the lesions . he has improved well and comes to us for regular follow - up .\nmucosal involvement is unusual in hhd and has been very rarely reported and can involve oral , conjunctival , vaginal , or in very rare instances esophageal mucosa .\nour patient had oral , pharyngeal , and genital mucosal involvement , which were resistant to the symptomatic treatment .\napart from the symptomatic therapy , drugs such as corticosteroids , dapsone , etretinate , methotrexate , cyclosporine , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , alefacept , psoralen plus ultraviolet a therapy and photodynamic therapy have been tried with varying results .\nas hhd is often recalcitrant to treatment , further options including invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd . in the study conducted by galimberti et al .\nhhd is linked to mutations in the calcium - transporting atpase type 2c member 1 gene encoding the human secretory pathway ca / mn atpase .\ntopical gentamicin was found to be very effective in inducing remission in a hhd patient carrying a premature stop mutation .\nit may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .\nmucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported .\nour patient had oral , pharyngeal , and genital mucosal involvement.thalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated . \n \nmucosal involvement is unusual in hailey - hailey disease ( hhd ) and has been very rarely reported .\nthalidomide may be an important alternative in the treatment of hhd in patients not responding to the other modalities of treatment or when the conventional drugs are contraindicated .", "answer": "familial benign chronic pemphigus or hailey - hailey disease ( hhd ) is a rare autosomal dominant disorder characterized by the development of recurrent blisters and erosions in the intertriginous areas . \n various topical and systemic treatment options include corticosteroids , topical 5-fluorouracil , topical vitamin d analogs , topical zinc oxide , dapsone , psoralen plus ultraviolet a , systemic retinoids , cyclosporine , methotrexate , and photodynamic therapy . in recalcitrant cases , further options including , invasive methods such as grenz ray therapy , carbon dioxide laser abrasion , and erbium : yag laser ablation , dermabrasion , electron beam therapy , botulinum toxin , and full - thickness excision of affected skin with repair by split - thickness grafting have been reported as useful in treatment of hhd . \n we describe a case of hhd who was treated with several treatment modalities including antibiotics , corticosteroids , and dapsone earlier and when presented to us had a severe recalcitrant disease . \n thalidomide , as a modality of treatment has been successfully used in few cases earlier . \n our patient responded well to thalidomide .", "id": 664} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nas is the most common cause of left ventricular outflow obstruction in children and adults . it is most common type of valvular heart disease in europe and north america , occurring in 27% of the population over 65 years of age .\nmedical therapy alone is not effective for the long - term management of aortic valve disease , thus valve replacement remains the standard of care in patients with an acceptable risk profile .\nwe present a case of critical as with significant symptom manifested as chest pain that was managed successfully without surgical avr or tavr .\nwe will also briefly review incidence , etiology , grading of as and current guidelines for avr .\na 91-year - old gentleman with history of hypertension , dyslipidemia and as presented to our office on 7/2015 with complaints of new onset sub sternal burning pain of 6 weeks duration .\nprior to 6 weeks patient could walk 2 blocks on level ground without shortness of breath or chest pain .\nblood pressure was 140/90 mm hg and pulse was regular at 60 beats per minute .\ncardiovascular exam revealed a grade 4/6 ejection systolic murmur best heard in the right second intercostal region radiating bilaterally to the neck .\necg revealed left ventricular hypertrophy ( lvh ) with non specific st - t wave changes in inferior leads ( figure 1 ) .\nechocardiography ( echo ) done in may of 2014 had revealed critical as with aortic valve area of 0.6 - 0.7 centimeter square and ejection fraction of 65 percent . the aortic valve ( av ) was heavily calcified .\naortic valve peak velocity ( av vmax ) 4.66 m / s ( figure 2 ) .\nthe patient was directly referred for a cardiac catheterization to evaluate his coronary anatomy prior to avr .\nhemodynamic measurement revealed left ventricle ( lv ) pressure 240/0 with left ventricular end diastolic pressure ( lvedp ) of 10 .\npulmonary artery wedge pressure ( pawp ) , mean of 24 , right atrium ( ra ) mean of 8 , right ventricle ( rv ) 60/10 with an right ventricular end diastolic pressure ( rvedp ) of 14 , pulmonary artery ( pa ) 60/17 .\nthe aortic valve area was calculated at 0.6 centimeter square , which was unchanged from echo done may 1 , 2014 .\nthe left ventriculogram in the right anterior oblique ( rao ) view revealed normal lv systolic motion and ejection fraction of 55 - 60 percent . left main coronary artery revealed a common ostium - giving rise to the left anterior descending ( lad ) and the circumflex .\nright coronary artery ( rca ) revealed a 99 % ostial narrowing ( figure 3 ) .\nlad revealed a 60 % narrowing in its proximal segment and a 90% ostial diagonal narrowing ( figure 4 ) .\nafter a detailed discussion involving the patient , his son , interventional cardiologist and the cardio thoracic surgeon , patient requested that only pci of the rca be considered , as the chest pain was of recent duration with no change in aortic valve finding .\nthus , a successful pci was done in the proximal rca with a bare metal stent ( figure 6 ) .\npatient did extremely well after pci of the rca and the patient has remained asymptomatic to date .\nthus , this new onset chest pain in patient with critical as was due to concomitant coronary artery lesion and was amenable to stenting and thus spared this elderly patient from the aortic valve replacement which would have been a high risk surgery for him .\nas is the most common valvular heart condition in the developed world , affecting 3% of people between ages 75 and 85 and 4% of people over age 85 .\ncongenitally unicuspid , bicuspid , tricuspid , or even quadricuspid valves may be the cause of as . in adults who develop symptoms from congenital as\nthe main causes of acquired as include degenerative calcification and , less commonly , rheumatic heart disease .\nother , infrequent causes of as include obstructive vegetations , homozygous type ii hypercholesterolemia , paget disease , fabry disease , ochronosis , and irradiation . based upon a variety of hemodynamic and natural history data\n, clinicians generally grade the severity of stenosis as mild , moderate , severe , or critical .\ngrading of as are as follows : i ) mild : valve area exceeds 1.5 cm ; transvalvular velocity 2.0 to 2.9 m / s ; mean gradient < 20 mmhg ; ii ) moderate : valve area of 1.0 to 1.5 cm ; transvalvular velocity 3.0 to 3.9 m / s ; mean gradient 20 to 39 mmhg ; iii ) severe : valve area is less than 1.0 cm ; transvalvular velocity 4 m / s ; mean gradient 40 mmhg .\nthe term critical stenosis was defined based upon theoretical considerations showing that the aortic valve area must be reduced to one - fourth of its natural size before significant changes in circulation occur . as a result , since the triangular orifice area of the normal ( adult ) aortic valve is approximately 3.0 cm , an area exceeding 0.75 cm would not be defined as critical .\navr and tavr remain the only treatment proven to reduce the rates of mortality and morbidity in this condition . under current guidelines , the onset of symptoms of exertional angina , syncope and dyspnea in a patient who has severe as is a class i indication for surgery .\nthe annual rate of sudden death in patients with this condition is estimated at 1% to 3% but the surgical mortality rate in avr has been as high as 6% . with improvements in surgical techniques and prostheses , mortality rates have been reduced to 2.42% making a case for earlier intervention .\ntavr has become widely available , but further investigation into its use in this patient cohort is warranted . while assessing the cases of asymptomatic as we have both traditional as well as novel markers at our disposal now . left ventricular ejection fraction ( lvef ) < 50 percent , peak aortic jet velocity > 4.0 m / s , valve area < 1 cm and mean pressure gradient > 40 mm hg are the traditional markers to denote severe as in asymptomatic patients . while , indexed left atrial size > 12.2 cm / m , lvh with wall thickness > 15 mm , global left ventricular longitudinal strain < 15.9 , bnp ( b - natriuretic peptide ) level > 130 pg / ml and increase in mean pressure gradient of > 20 mm hg during exercise testing are the novel markers of asymptomatic severe as .\nbnp level does not appear to be significantly associated with the degree of as severity but does reflect heart failure status .\nthe american college of cardiology and american heart association ( acc / aha ) have issued the following recommendations for avr , based on the severity of stenosis and on whether the patient has symptoms : i ) severe stenosis , with symptoms : class i recommendation ( surgery should be done ) . without surgery ,\nthese patients have a very poor prognosis , with an overall mortality rate of 75% at 3 years ; ii ) severe stenosis , no symptoms , in patients undergoing cardiac surgery for another indication ( example coronary artery bypass grafting , ascending aortic surgery , or surgery on other valves ) : class i recommendation for concomitant aortic valve replacement ; iii ) moderate stenosis , no symptoms , in patients undergoing cardiac surgery for another indication : class iia recommendation ( i.e. , aortic valve replacement is reasonable ) ; iv ) very severe stenosis ( aortic peak velocity > 5.0 m / s or mean pressure gradient 60 mm hg ) , no symptoms , and low risk of death during surgery : class iia recommendation ; v ) severe stenosis , no symptoms , and an increase in transaortic velocity of 0.3 m / s or more per year on serial testing or in patients considered to be at high risk for rapid disease progression , such as elderly patients with severe calcification : class iib recommendation ( surgery can be considered ) .\non revisiting the above case description we realize that the patient did have critical as but was asymptomatic .\nhis chest pain was only due to concomitant coronary artery disease but was not due to as per se .\nage and comorbidity of the patient posed a high risk for coronary artery bypass graft ( cabg ) with avr .\nbesides , the patient s symptoms were of new onset and subsequent cardiac catheterization revealing critical rca stenosis and the patient s preference for treating the cause of his recent symptoms , encouraged us to think otherwise . the decision to perform pci alone with the belief that this chest pain and cad would be amenable to the minimal risk procedure paid dividends .\nin addition , patient received a bare metal stent with the option of undergoing surgical avr if symptoms were not relieved .\nawareness amongst physicians about the fact that all critical aortic stenosis with chest pain may not require aortic valve replacement is important .\nthis can lead to less invasive treatment tailored to the need of the patient especially in those with advanced age , significant comorbidities and an extremely high risk for cabg with avr and can also result in decreased cost of care .\npharmacological nuclear stress testing may be another modality that can be used to differentiate etiology of the symptoms .", "answer": "aortic valve replacement ( avr ) remains the cornerstone of treatment for symptomatic critical aortic stenosis ( as ) . \n it is a class i indication that symptomatic patients with critical as undergo either surgical or transcatheter aortic valve replacement ( tavr ) . \n we present a patient with critical as and new angina that was managed successfully with percutaneous coronary intervention ( pci ) of the right coronary artery . \n physicians should consider that not all patients with critical as and angina necessarily require avr . \n concomitant pathology leading to the symptoms should be carefully ruled out . \n this leads to a less invasive , cost effective care plan especially in patients with advanced age and comorbidities for which any type of surgical valvular intervention may pose high risk .", "id": 665} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbullous systemic lupus erythematosus ( bsle ) is a subepidermal blistering disease that occurs in a subset of patients with systemic lupus erythematosus ( sle ) [ 1 , 2 ] .\ncutaneous lesions are reported during the course of sle in 76% of patients ; however , it has been reported that bsle is very rare and occurs in less than 1% of patients with sle [ 35 ] .\nclinically , in addition to the features of sle , the bsle patients especially present with a rapid , widespread development of tense fluid - filled vesicles and bullae .\nmoreover , this blistering disease may vary from a small group of vesicles to large tense blisters with urticarial eruptions , erosions , itching , and crustations .\nhistologically , bsle is characterized by a subepidermal blister , with a predominantly neutrophilic dermal infiltrate and only occasional eosinophils .\nfurthermore , immunofluorescence examination showed linear deposition of lgg , lga , c3 , and c1q along the basement membrane zone [ 5 , 6 ] .\nbecause of the particularly clinical and histological presentation of bsle , camisa and sharma proposed diagnostic criteria for bsle ; these include a diagnosis of sle based on the following criteria of the acr ; vesicles and bullae mainly located on sun - exposed areas ; the histopathology is characterised by subepidermal bullae with microabscesses of neutrophils in the dermal papillae , similar to those found in dermatitis herpetiformis and deposition of igg , igm , or both and often iga in the basement membrane zone .\nalthough blse may exhibit any of the symptoms associated with sle , the onset and course of blistering eruption do not necessarily parallel the activity of the systemic involvement .\nfurthermore , the therapeutic options for sle are not usually fit for bsle [ 9 , 10 ] . in some cases\n, the eruption flared after systemic corticosteroid administration for sle [ 11 , 12 ] .\nhowever , most of the patients have a striking therapeutic response to dapsone [ 1316 ] . a response may be seen with very small doses of dapsone . in the case of the present paper ,\nother drugs such as cyclophosphamide , azathioprine , and mycophenolate mofetil and biologic drugs may also be effective for bsle treatment . in the part of literature review , we provide a review of all the available treatment options for bsle .\nsteroids and antimalarials are the standard treatments for the cutaneous manifestations of sle . in unresponsive patients , azathioprine and high dose or pulse steroids , cyclosporin , and pulse cyclophosphamide are the most commonly used alternative therapies [ 1820 ] .\ndapsone is less used in the control of the sle rash but has a dramatic improvement in the eruption of bsle patients [ 15 , 16 ] .\nwe also found that a 22-year - old woman with bsle had multiple tense vesiculobullous lesions on the face , trunk , and limb ( figure 1 ) .\na biopsy from the upper limb showed a subepidermal blister with a predominantly neutrophilic dermal infiltrate and only occasional eosinophils ( figure 2(a ) ) .\nimmunofluorescence showed a granular band of c1q , c3 , and igg at the basement membrane ; less iga and igm were observed ( figures 2(b)2(f ) ) .\nthe skin condition showed no response in the methylprednisolone , while a considerable improvement after dapsone administration was observed .\nregarding the special clinical feature and the discriminative therapies from the sle treatments , we review all the available treatment for bsle .\ndapsone is a sulfone that has played a critical role in the eradication of leprosy . besides , a number of cutaneous eruptions are effectively controlled by dapsone . due to these eruptions that are largely characterized by the presence of cutaneous neutrophilic dermal infiltrate , such as dermatitis herpetiformis and the inflammatory variant of epidermolysis bullosa acquisita\n, the mechanism of its anti - inflammatory action mainly relies upon its inhibition of the functions of polymorphonuclearleukocytes and of complement activation via the alternative pathway that has been postulated [ 15 , 23 ] .\nalthough a new or recurrent rash was considered a factor of sle disease activity index , the eruption of bsle was not constantly associated with a flare of sle .\nconsequently , because of being unparallel with the disease activity , the eruption of bsle patients is often unresponsive to corticosteroid therapy . due to the striking histologic resemblance to dermatitis herpetiformis\n, the patients who were treated with dapsone ( 2 mg / kg / day ) usually obtained a dramatic improvement in the eruption .\npatients tend to have an efficacious response with cessation of new blister formation in 1 - 2 days and healing of existing lesions within several days . a relatively low dose ( 2550 mg ) has also been shown to have a response [ 1 , 15 , 24 ] .\ninterestingly , improvement of the eruption did not correlate with amelioration of the systemic manifestations .\nthe dramatic response to dapsone therapy demonstrated that dapsone is useful in treating bullous lesions of sle [ 5 , 15 , 16 , 26 ] .\nnotably , the blistering eruption was not improved by dapsone in some cases , and even worsening has been noted after its administration . it has been reported that patients with bsle , who initially presented with lesions clinically resembling erythema multiform , experienced exacerbation of their disease with dapsone [ 2729 ] .\nfurthermore , dapsone has been assigned to pregnancy category c ; bsle patients with pregnancy might not be fit for administration of this drug .\nhemolysis and hepatic and renal toxicity usually accompany administration of the drug in a dose related fashion [ 3134 ] ; therefore its clinic use was confined and a careful monitoring of its toxicity is required .\ncorticosteroids are usually required to improve clinical symptoms and laboratory abnormalities and are still a mainstay for inducing remission in sle patients [ 18 , 20 , 35 ] .\nunexpectedly , many bullous sle patients tend to be unresponsive to systemic corticosteroid therapy that has been described .\nfurthermore , in some cases of sle patients , the eruption flared a few days after systemic corticosteroid administration [ 11 , 12 ] .\ninterestingly , some patients responded effectively to corticosteroids , although they required relatively high doses .\na patient with sle who presented with vesiculobullous lesions during the third trimester of pregnancy has been presented .\na skin biopsy of this patient was performed , and it showed significant necrosis of keratinocytes in the epidermis and granular , dense , and continuous deposits of moderate igg positivity in the basement membrane zone .\ndapsone has been assigned to pregnancy category c. the pregnant woman treated with high - dose corticosteroids obtained a satisfactory response .\nas the dapsone administration often causes hepatic and renal toxicity [ 32 , 33 , 3840 ] , prednisone alone or in combination with low doses dapsone might be the treatment of choice for these bsle patients .\nthese observations demonstrated that corticosteroids may act as an alternative treatment for bsle when patients are unresponsive or unfit for other drugs .\nbiologic agents , such as infliximab , rituximab , and anakinra , have emerged as effective therapies for treating a wide spectrum of diseases which includes various rheumatic , gastrointestinal , and cutaneous diseases [ 4144 ] .\nthe involvement of all of the key components ( especially cytokines and immune cells ) of the immune system in the pathogenesis of sle offers many potential targets for therapeutic management of this disease .\nb cells , a critical immune cell , which can act as antigen - presenting cells , differentiate into plasma cell to produce pathogenic autoantibodies and secrete various cytokines and chemokines in the immune response [ 45 , 46 ] .\nthese functions of the b cell support the fact that it plays an important role in the development of pathogenesis of sle . therefore , use of b cell depletion therapy in sle has emerged as a novel and promising therapeutic alternative for sle patients [ 4749 ] .\nrituximab which is a chimeric monoclonal antibody that reacts with cd20 , an antigen that is present on immature , naive , and memory b cells but not on mature plasma cells , has been approved in the treatment of sle . up to now\nthe patient was treated with hydroxychloroquine ( hcq ) twice daily , mycophenolate mofetil 1000 mg / d , and varying doses of corticosteroids , while the eruption was not improved .\ndapsone and azathioprine were added but had to be stopped because of elevated liver enzymes and leukopenia .\nmycophenolate mofetil was increased to 2000 mg / d , but her skin disease remained active .\nthe skin lesions improved within 10 days after the first dose and cleared by day 15 after the second dose . furthermore , prednisone was successfully tapered , and the patient has remained free of recurrence of cutaneous and oral blistering lesions .\nthe results of this case suggest a potential role for treatment of refractory bsle with rituximab .\nmethotrexate ( mtx ) has been widely proved to be an effective agent in control of the rheumatoid arthritis .\nit has proved that mtx was beneficial in sporadic cases of scle refractory to therapy with conventional therapy [ 5254 ] , such as antimalarials and corticosteroids .\nfurthermore , in a randomized and double - blind trial in 41 patients with sle , mtx reveals a role for controlling the skin lesions in 75% of cases , with a mean reduction of prednisone dose of 44% .\nthese reports demonstrated that mtx could represent a valid therapeutic option in controlling the cutaneous sle and in sparing the steroid dose .\nhowever , bsle is a subepidermal blistering disease that occurs in a subset of patients with systemic lupus erythematosus ( sle ) .\ncutaneous lesions of bsle are reported during the course of sle in less than 1% of patients , while lesions are not in line with the disease activity .\n, a rapid and full resolution of cutaneous lesions was obtained with methotrexate alone . a case of 40-year - old female with systemic lupus erythematosus ( sle ) developed a severe bullous eruption on sun - exposed areas , while the previous manifestations of the disease were quiescent . in consideration of prior intolerance to many drugs ,\nhcq is a commonly used drug for controlling the cutaneous lesions and the disease activity of the sle [ 58 , 59 ] , while it does not act effectively in the eruption of bsle .\nthe conventional treatment for sle only revealed modest improvement in steroids and antimalarials . although cyclophosphamide has been shown to produce moderate improvement of skin lesions of sle , the beneficial role in bsle has not been demonstrated .\nmycophenolate mofetil ( mmf ) has been widely used for suppressing the lupus activity , while it also was not valid for bsle , even at a high dose [ 10 , 37 ] . in cases nonresponsive to dapsone\n, the eruption has been controlled by prednisone or with combination therapy of prednisone and azathioprine .\nin the treatment of bullous sle , dapsone is the effective basic therapy , and it often induces a dramatic response . in some cases , where an adequate response is not achieved with dapsone or the sle disease activity index is high , other immunosuppressants , such as prednisolone , methotrexate , and azathioprine , can be used for controlling the eruption and suppressing the systemic symptoms . moreover , in some special case , where dapsone administration or other chemical drugs ( mtx , azathioprine , etc . )", "answer": "bullous systemic lupus erythematosus ( bsle ) is an autoantibody - mediated vesiculobullous disease in patients with sle . \n autoimmunity in bsle is characterized by the presence of circulating anti - type vii collagen antibodies . \n bsle patients often present with multiple , tense , clear fluid - filled vesicles and bullae overlying erythematous edematous plaques . \n skin biopsy from bsle patients shows subepidermal bullae with numerous neutrophils and only occasional eosinophils . \n furthermore , immunofluorescence examination showed linear deposition of lgg , lga , c3 , and c1q along the basement membrane zone . \n bsle patients with corticosteroids treatment constantly do not receive a marked improvement , while dapsone generally dramatically improved the skin condition . \n recently , it has been reported that quite a few cases of bsle were successfully treated with other immune suppressive drugs . \n therefore , a comprehensive review of the treatment of bsle would be beneficial to cure the disease .", "id": 666} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe facial nerve trunk exits through the stylomastoid foramen , and enters the parotid gland where it divides into the cervicofacial and temporofacial divisions . then divides into five peripheral branches to supply the muscles of facial expression ( 1 ) .\nthe branches arising from the rami form to parotid plexus in parotid gland . the superior buccal nerve arising from temporofacial ramus and the inferior buccal nerve arising from the cervicofacial ramus form to the buccal plexus without parotid gland ( 1 ) . the zygomatic ( 2 ) , the marginal mandibular ( 3 - 5 ) , the buccal ( 6 ) , and the temporal branches ( 7 ) of the facial nerve were investigated by many researchers . different surgical approaches and landmarks to the trunk of the facial nerve have been reported ( 8 - 12 ) .\nmany landmarks such as the mastoid process ( 8 - 10 ) , the transverse process of the atlas ( 8) and axis ( 11 ) , the temporomandibular joint , the angle of the mandible ( 9 , 11 ) , insertion of the sternocleidomastoid muscle , pointer cartilage of the ear ( 10 ) , tragal pointer ( 11 ) and the marginal mandibular branch of the facial nerve ( 12 ) can be used to identify the trunk of the facial nerve . but\nidentification of this trunk may be difficult because it is encompassed by dense connective tissue ( 13 ) . in this paper\nthe double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic fissure was found in a 65-yr - old caucasian male cadaver during a routine dissection course .\nfirstly , the skin and superficial fascia between the mastoid process and ramus of the mandible were reflected in all subjects .\nthe anterior border of the parotid gland was carefully elevated and the rami of the nerves followed proximally up to the stylomastoid foramen under a stereomicroscope ( stemi 2000 ; carl zeiss , jena , germany ) .\nfinally , magnetic resonance ( mr ) imaging was performed by using 1.5 t scanner to this cadaver . to be able to demonstrate the stylomastoid foramen and the petrotympanic fissure in same section\n, we obtained t1 and t2 weighted oblique sagittal scans . in the present cadaver , difference with the exit point of the facial nerve was observed . in this specimen ,\nin this side , although cervicofacial ramus of the facial nerve exited from the stylomastoid foramen , temporofacial ramus of the facial nerve exited from petrotympanic fissure ( fig .\nthe buccal branch dividing from temporal branch of temporofacial ramus and first buccal branch dividing from cervicofacial ramus formed to first buccal plexus .\nthe buccal branch dividing from zygomatic branch of temporofacial ramus and second buccal branch dividing from cervicofacial ramus formed to second buccal plexus ( fig .\n2 ) . these two buccal plexuses and other branches formed to structures like to polygon ( fig .\nthe temporofacial ramus exiting from petrotympanic fissure was seen on magnetic resonance image ( fig .\nseveral studies relating to the trunk of the facial nerve have been reported in the literature ( 14 - 19 ) .\nkatz and catalano ( 14 ) reported three cases ( 3% ) presenting two main trunks , known as the major and minor trunks , with the latter joining the larger temporofacial division , the origin of the main buccal branch .\nthe minor trunk of the facial nerve was noted in eight of 30 cases ( 26.7% ) and , in all of them , the minor trunk entered the lower division of the facial nerve ( 15 ) .\nbotman and jongkees ( 16 ) reported that the facial nerve within the mastoid segment of the temporal bone can split into two or three branches , and each branch exits through a separate osseous foramen . in this study ,\na trunk of the facial nerve exiting from the petrotympanic fissure is present one case .\nin addition , baker and conley ( 17 ) reported the possibilities of trifurcation , quadrifurcation , or even a plexiform branching pattern of the trunk of the facial nerve .\nsalame et al . ( 18 ) identified one case of trifurcation out of 46 cases .\nbut we did not identify any case of trifurcation , quadrifurcation or a plexiform branching pattern of the trunk .\nthe facial nerve can easily be injured by sharp or penetrating trauma to the cheek .\nthere are number of studies concerning protection extracranial branches of the facial nerve during plastic surgery procedures and operations intended for the parotid gland , but relatively little care has been given exit point of the facial nerve .\nknowledge of the trunk of the facial nerve is essential for preserving the nerve during surgical procedures of the mastoid process , parotid gland , the cranial base and the facial nerve ( 13 , 17 ) . in this study , we exposed exit point of the trunk of the facial nerve through the cranium .\nsurgeons should be aware of the possible anatomical variations of the trunk of the facial nerve , because a trunk of the facial nerve exiting from the petrotympanic fissure may also be present .", "answer": "there are several studies concerning branches of the facial nerve , but we encountered less information about the trunk of the facial nerve in the literature . during the routine dissection of a 65-yr - old caucasian male cadaver , double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic fissure were encountered . \n because of an extremely rare variation , we presented this case report . \n in addition this cadaver had two buccal plexuses . \n these plexuses and other branches were formed to structures like to polygon . \n these anatomic peculiarities were described , photographed and illustrated . \n finally , magnetic resonance imaging was performed by using 1.5 t scanner to this cadaver . \n the facial nerve trunk can be damaged during surgical procedures of the parotid gland tumours and submandibular region . \n surgeons who are willing to operate on this area should be aware of the possible anatomical variations of the facial nerve trunk .", "id": 667} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nstrains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 .\ncells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen .\nfrozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 .\nground powder was hydrated in proteasome buffer ( 50 mm tris - hcl [ ph7.5 ] , 5 mm mgcl2 , 1 mm edta , and 10% glycerol ) supplemented with 2 mm atp , protease inhibitor tablets ( complete , roche ) , 2 mm pmsf , 1 mm benzamidine , 10 g / ml pepstatin a , and 1 g / ml antipain .\ncell extracts were cleared at 30,000 g for 30 min at 4c , and the supernatants were mixed with rabbit igg resin ( cappel , mp biomedicals ) for 90 min at 4c .\nresins were collected at 900 g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone .\nbp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c .\neluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .\nstrains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 .\ncells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen .\nfrozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 .\nground powder was hydrated in proteasome buffer ( 50 mm tris - hcl [ ph7.5 ] , 5 mm mgcl2 , 1 mm edta , and 10% glycerol ) supplemented with 2 mm atp , protease inhibitor tablets ( complete , roche ) , 2 mm pmsf , 1 mm benzamidine , 10 g / ml pepstatin a , and 1 g / ml antipain .\ncell extracts were cleared at 30,000 g for 30 min at 4c , and the supernatants were mixed with rabbit igg resin ( cappel , mp biomedicals ) for 90 min at 4c .\nresins were collected at 900 g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone .\nbp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c .\neluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .", "answer": "substrates of the proteasome are recognized and unfolded by the regulatory particle ( rp ) , then translocated into the core particle ( cp ) to be degraded1 . \n a hetero - hexameric atpase ring , containing subunits rpt1-rpt6 , is situated within the base subassembly of the rp1 . \n the atpase ring sits atop the cp , with the rpt c - termini inserted into pockets in the cp26 . \n we have identified a novel function of the rpt proteins in proteasome biogenesis through deleting the c - terminal residue from each rpt . \n our results indicate that assembly of the hexameric atpase ring is templated on the cp . \n we have also identified an apparent intermediate in base assembly , bp1 , which contains rpn1 , three rpts , and hsm3 , a chaperone for base assembly . \n the rpt proteins with the strongest assembly phenotypes , rpt4 and rpt6 , were absent from bp1 . \n we propose that rpt4 and rpt6 form a nucleating complex to initiate base assembly , and that this complex is subsequently joined by bp1 to complete the rpt ring . \n our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process .", "id": 668} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbaseline flt imaging in this patient with metastatic malignant melanoma demonstrated splenic ( s ) , peritoneal ( p ) and bm metastases .\nafter 14 days of treatment with a novel antiangiogenesis agent the upper abdominal peritoneal deposit ( vertical arrow ) had substantially decreased activity while the lower abdominal focus could no longer be visualised . uptake at sites of baseline abnormality in the spleen ( horizontal arrow ) and right femoral bm ( oblique arrow ) were relatively photopaenic compared to adjacent normal tissues . fdg pet scanning ( not shown ) demonstrated no change over the same period . \nmost clinical studies of hypoxia imaging have utilized the nitroimadozole , [ f]fluoromisonidazole ( fmiso ) .\nslow blood pool clearance and high lipophilicity contribute to significant background activity and relatively low contrast between hypoxic and normal tissues . a new agent\n[ f]fluoro - azomyacinarabinofuranoside ( faza ) has lower lipophilicity as demonstrated by low brain uptake in the left panel .\nmore rapid blood clearance with similar absolute uptake in hypoxic tissue leads to higher contrast as demonstrated in this comparative study of faza ( left ) and fmiso ( right ) scans in a patient with locally advanced retropharyngeal cancer .", "answer": "despite the excellent clinical performance of fluorodeoxyglucose ( fdg ) as a cancer - imaging agent for positron emission tomography ( pet ) , false positive and false negative results can be problematic in some clinical settings . \n radiopharmaceutical development has recently focussed on the search for new pet tracers that could complement or replace fdg in such settings . due to the general availability and favourable physical properties of fluorine-18 \n , much effort has been directed to fluorinated compounds . \n the most promising of these are discussed .", "id": 669} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary plasma cell leukemia ( ppcl ) is a very aggressive form of plasma cell disorder .\nppcl is very rare , reported in only 4 - 6% of patients with multiple myeloma ( mm ) .\nppcl is defined as the presence of more than 20% plasma cells in the peripheral blood and an absolute plasma cell count greater than 2 10/l , without previous evidence of mm .\nconsistent with the high tumor burden , extramedullary involvement , such as hepatosplenomegaly , lymphadenopathy , soft - tissue plasmacytomas , or leptomeningeal infiltration , is more frequent in ppcl than in mm . despite the development of new agents , such as proteasome inhibitors or immunomodulatory drugs ( imids ) , for plasma cell disorders , the median overall survival of ppcl\nalthough ppcl is difficult to treat , high - dose melphalan followed by autologous stem cell transplantation ( auto - sct ) and/or allogeneic stem cell transplantation ( allo - sct ) seems to improve outcomes in younger selected patients .\nhowever , patients with ppcl who had central nervous system ( cns ) relapse after auto- and/or allo - sct were refractory to various treatments , and had an extremely poor prognosis .\nwe herein present a ppcl patient with cns relapse after allo - sct who underwent concurrent intrathecal therapy ( it ) and radiotherapy ( rt ) followed by maintenance therapy with pomalidomide and low - dose dexamethasone ( pd ) .\na 46-year - old man without a previous significant medical history was referred to our hospital with complaints of anorexia and generalized fatigue .\nlaboratory findings revealed significant abnormalities , including a white blood cell ( wbc ) count of 19.710/l with 45% plasma cells , a hemoglobin level of 11.6 g / dl , a platelet count of 7.010/l , a creatinine level of 7.63 mg / dl , and a ldh level of 301 iu / l ( table 1 ) . on a peripheral blood smear ,\nthe plasma cells were medium - sized , with round nuclei , basophilic cytoplasm , and occasional cytoplasmic vacuoles ( figure 1a ) .\ng / l , and the serum free light chain ( flc ) k/ ratio was 161.11 ( table 1 ) . in this case , a m - component of the igg - k type was identified by serum protein electrophoresis .\nmoreover , flow cytometry on the peripheral blood showed that these plasma cells were positive for cd38 , cd49e , cd54 , cd138 and cytoplasmic kappa light chain .\nt(11;14)(q13;q32 ) in 9 metaphase cells ( figure 1b ) and 46,xy in 11 metaphase cells , and a fluorescent in situ hybridization analysis revealed ccnd1/igh gene fusion rearrangement .\nthe patient was admitted to an intensive care unit ( icu ) for continuous hemodiafiltration ( chdf ) . on the same day\n, we started induction therapy with lenalidomide ( 15 mg / day orally on days 1 - 14 ) , bortezomib ( 1.3 mg / m subcutaneously on days 1 , 4 , 8 , and 11 ) , and low - dose dexamethasone ( 20 mg / day orally on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , and 12 ) , also known as rvd induction therapy , each for a 21-day cycle .\neight days after starting the induction therapy , the circulating plasma cells in the peripheral blood disappeared , and he was transferred from the icu after withdrawal of chdf . after a total of 3 cycles of chemotherapy , the laboratory abnormalities markedly subsided , consistent with a very good partial response ( vgpr ) , because serum immunofixation was positive .\nhe and his family consented to undergo allo - sct . at our outpatient department , because of grade 2 peripheral neuropathy , he continued induction therapy with lenalidomide ( 25 mg / day orally on days 1 - 14 ) , bortezomib ( 1.3 mg / m subcutaneously on days 1 and 8) , and dexamethasone ( 20 mg / day orally on days 1 and 8) in each 21-day cycle . after a total of 6 courses ,\nallo - sct was performed with the bone marrow from an unrelated donor ( hla - a one allele mismatch ) .\nthe conditioning regimen consisted of fludarabine 120 mg / m ( 30mg / m on day -5 , -4 , -3 , and -2 ) , melphalan 180 mg / m ( 90mg / m on day-4 and -3 ) , and rabbit anti - thymocyte globulin 2.5 mg / m ( 1.25mg / m on day -2 and -1 ) .\nfor the prevention of graft - versus - host - disease ( gvhd ) , tacrolimus was started from day -1 , and methotrexate was given on days 1 , 3 , and 6 .\ncomplete donor chimerism was detected in the bone marrow on day 29 . during this admission ,\nhowever , serum immunofixation was positive despite normal igg and flc levels ; therefore , he was still considered to have a vgpr .\ntwo months after discharge , the patient developed cervical , mediastinal , and axillary lymphadenopathy .\nhe was therefore diagnosed with ebv - associated lymphoproliferative disease and was immediately treated with 2 cycles of rituximab monotherapy , resulting in a complete response .\ntacrolimus was discontinued on day 180 , and there was no evidence of chronic gvhd .\nhowever , 6 months after allo - sct , he had marked cytomegalovirus ( cmv ) antigenemia .\nthe protein level in the cerebrospinal fluid was 53 mg / dl , and the glucose level was 55 mg / dl ; 17 monocytes per microliter were detected .\ncytological examination revealed that some of these cells resembled plasma cells ( figure 2a ) .\nmagnetic resonance imaging ( mri ) with gadolinium ( gd ) enhancement revealed a small , enhanced nodule in the lateral medulla oblongata ( figure 2b , arrowhead ) . enhanced computed tomography ( ct ) showed no extramedullary tumors .\nmoreover , we still observed complete donor chimerism , without leukemic plasma cells , in his bone marrow .\nthe patient underwent 4 courses of weekly it , consisting of methotrexate 15 mg , cytarabine 20 mg , and prednisolone 40 mg in combination with local cranial rt ( 5 fractions of 2 gy for a total dose of 10 gy ) . after this combined treatment , his neurological symptoms resolved and the plasma cells in the cerebrospinal fluid disappeared . to prevent cns recurrence , we administered pomalidomide 4 mg / day on days 121 , with 20 mg of dexamethasone weekly for each 28-day cycle .\nsubsequently , a reduced dose of 2 mg was administered for 2 cycles , but grade 4 neutropenia occurred again .\nhe resumed pomalidomide at 1 mg and continued the low dose without severe hematological abnormalities .\ntwelve months after the cns relapse , both enhanced ct and brain mri with gd enhancement revealed no extramedullary tumors . in our outpatient follow - up , he maintained vgpr without major complications for more than 18 months after the diagnosis of cns relapse .\nthe prognosis of plasma cell disorder has improved following the introduction of new agents and the development of sct , but a cure remains elusive .\nthe long - term survival rate of ppcl is low due to the aggressive nature of the disease that comprises high tumor burden and extramedullary involvement . in the us ,\nupfront allo - sct is still one of the treatment options for young ppcl patients without major complications . in our study , we performed upfront allo - sct with a myeloablative - conditioning regimen for our young patients without major complications .\nthe center for international blood and marrow transplant research ( cibmtr ) conducted a retrospective sct study in ppcl , and demonstrated high survival rates in an autologous group compared with those in an allogeneic group . in the cibmtr study ,\nnon - relapse mortality in the allogeneic group was much higher at 3 years ( 42% vs. 5% ) , despite this group possessing a lower relapse rate ( 39% vs. 61% ) .\nour patient survived for more than 2 years after allo - sct , although he unfortunately suffered from cns relapse on day 350 .\nconsolidation and maintenance therapy after auto- and/or allo - sct in plasma cell disorder is still controversial .\nhowever , some clinical trials have recently shown that lenalidomide maintenance after auto - sct for mm significantly prolonged progression - free survival ( pfs ) and overall survival . moreover\n, a prospective clinical trial by the intergroupe francophone du mylome group showed that a bortezomibbased regimen followed by auto - sct and subsequent maintenance therapy with lenalidomide , bortezomib , and dexamethasone for ppcl significantly improved pfs compared with those who received a reduced intensity conditioning allograft . in the future\n, auto - sct and maintenance therapy combined with novel agents may be a treatment option for young ppcl patients .\nthe prognosis of plasma cell disorders with cns involvement is extremely poor . in a retrospective study on cns\nmyeloma conducted in 12 greek institutions , there was no significant difference in median survival of cns myeloma ( called post cns - mm ) between novel drug - treated patients and those given other treatments ( 4 months vs. 2 months ) . by multivariable analysis ,\nextramedullary lesions , prior to treatment with novel drugs , and high ldh levels at myeloma diagnosis were statistically independent predictors of post cns - mm survival .\nthese findings corroborate our observations that our patient with cns relapse of ppcl had an extremely short - term outcome .\nit has been reported that 19% of post cns - mm patients met the criteria for ppcl .\nfurthermore , some of these ppcl patients developed isolated cns relapse during systemic remission after auto - sct . in a prospective study by royer et al .\n, 2 ppcl patients experienced neuromeningeal relapse after autologous- and allo - sct , respectively , and both patients soon died despite intrathecal chemotherapy . in the present case , although vgpr was maintained by rvd induction therapy followed by allo - sct , isolated cns relapse occurred within 1 year .\nseveral drugs used in multiple myeloma , including bortezomib and lenalidomide , do not efficiently cross the blood \nof note , bbb penetration of lenalidomide was 11% in a rhesus monkey model , whereas that of thalidomide was 42% . in a murine model , pomalidomide displayed 39% bbb penetration and high anti - tumor activity in the cns . to the best of our knowledge ,\nthe anti - tumor effect of thalidomide is inferior to that of pomalidomide . additionally , pomalidomide is more effective in ameliorating extramedullary involvement . in our case ,\nconcurrent it and rt followed by pd was initiated after the diagnosis of isolated cns involvement after allo - sct .\nin addition , maintenance therapy by pd might prolong survival to prevent systemic recurrence , including cns involvement , for more than 18 months .\nthe role of pomalidomide for ppcl patients with cns involvement should be further explored in clinical trials .\nour ppcl patient received rvd induction therapy followed by up - front allo - sct .\nhowever , concurrent it and rt followed by pomalidomide - based maintenance therapy well controlled his cns recurrence and prolonged his survival . to find an optimal treatment for this rare but aggressive ppcl , prospective clinical trials for this disorder should take into account the importance of myeloma drug penetration across the bbb in order to enhance the treatment of cns recurrence", "answer": "primary plasma cell leukemia ( ppcl ) is a rare aggressive variant of plasma cell disorder and frequently presents with extramedullary disease . \n central nervous system ( cns ) involvement with ppcl has an extremely poor prognosis . \n we describe a 46-year - old man with ppcl treated with a combination of lenalidomide , bortezomib , and dexamethasone as induction therapy following upfront allogeneic stem cell transplantation ( allo - sct ) . despite achieving a very good partial response \n , the patient suffered from an isolated cns relapse 12 months after allo - sct . \n he was immediately started on concurrent intrathecal chemotherapy ( it ) and cranial irradiation ( rt ) . \n subsequently , pomalidomide and low - dose dexamethasone ( pd ) were given as maintenance therapy . \n he has been without cns recurrence for more than 18 months . \n our case suggests that concurrent it and rt followed by pd maintenance therapy may be an effective option to control cns relapse of ppcl after allo - sct .", "id": 670} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nall chemicals and reagents were of high performance liquid chromatography ( hplc ) or analytical grade .\npyrrole ( 99 % ) , thiophene ( 99 % ) , and tetrabutylammonium perchlorate ( 98 % ) were purchased from sigma - aldrich ( schnelldorf , germany ) .\nmedical steel wires ( ni cr , = 750 m ) were purchased from b. braun surgical s.a .\npolypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique .\nthe three - electrode cell was filled with electrolyte solution consisting of 100 mm pyrrole / thiophene ( fig . 4 ) and 250 mm tetrabutylammonium perchlorate in acetonitrile.fig . \n4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5 v and seven scans\nsecond , an additional 14 scans in the higher potential range from 0.2 to 2.7 v were used ( fig . \n5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b ) the morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector .\nsmall angle x - ray scattering ( saxs ) data were collected using a nanostar system ( bruker axs gmbh , karlsruhe , germany ) with pinhole collimation and a two - dimensional hi star detector with resolution of 1,024 1,024 pixels , mounted on an x - ray tube with a copper anode and equipped with crossed gbel focusing mirrors .\nsamples were mounted between two mica windows in sample holders with thickness of 1 or 2 mm .\nthe sample - to - detector distance was 650 mm , and the exposure time for a single frame was 10,000 s. each sample was measured three times , and the obtained data were averaged .\nthe saxs data were recorded within the scattering vector range of 0.15 nm < s < 3.5 nm ( where s = 4sin/ , 2 is the scattering angle , and is the x - ray wavelength ) .\nthe saxs data were corrected for the detector response and normalized to the intensity of the incident beam , and the background scattering ( empty holder ) was subtracted using the saxs_nt v4.1 program package ( bruker axs gmbh , karlsruhe , germany ) .\nelectropolymerization was performed using a homemade electrochemical cell coupled with a high performance potentiostat galvanostat ( pgstat128n series ; metrohm - autolab b.v . ,\nall chemicals and reagents were of high performance liquid chromatography ( hplc ) or analytical grade .\npyrrole ( 99 % ) , thiophene ( 99 % ) , and tetrabutylammonium perchlorate ( 98 % ) were purchased from sigma - aldrich ( schnelldorf , germany ) .\nmedical steel wires ( ni cr , = 750 m ) were purchased from b. braun surgical s.a .\npolypyrrole ( ppy ) and polythiophene ( pth ) coatings were synthesized by electropolymerization with a linear sweep voltammetry technique .\nthe three - electrode cell was filled with electrolyte solution consisting of 100 mm pyrrole / thiophene ( fig . 4 ) and 250 mm tetrabutylammonium perchlorate in acetonitrile.fig . \n4chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings chemical structures of ppy ( a ) and pth ( b ) spme fiber coatings polymerization was performed using medical steel wires as working electrodes . an ag / ag electrode was applied as a reference electrode , with platinum net bent into a cylinder as a counterelectrode . for ppy , a potential range from 0.2 to + 2.5 v and seven scans\nsecond , an additional 14 scans in the higher potential range from 0.2 to 2.7 v were used ( fig . \n5electropolymerization of pyrrole ( a ) and thiophene ( b ) electropolymerization of pyrrole ( a ) and thiophene ( b )\nthe morphologies of the polypyrrole and polythiophene fibers were investigated using a scanning electron microscope ( leo 1430vp ; carl zeiss smt , oberkochen , germany ) coupled with a backscattered electron ( bse ) detector .\nsmall angle x - ray scattering ( saxs ) data were collected using a nanostar system ( bruker axs gmbh , karlsruhe , germany ) with pinhole collimation and a two - dimensional hi star detector with resolution of 1,024 1,024 pixels , mounted on an x - ray tube with a copper anode and equipped with crossed gbel focusing mirrors .\nsamples were mounted between two mica windows in sample holders with thickness of 1 or 2 mm .\nthe sample - to - detector distance was 650 mm , and the exposure time for a single frame was 10,000 s. each sample was measured three times , and the obtained data were averaged .\nthe saxs data were recorded within the scattering vector range of 0.15 nm < s < 3.5 nm ( where s = 4sin/ , 2 is the scattering angle , and is the x - ray wavelength ) .\nthe saxs data were corrected for the detector response and normalized to the intensity of the incident beam , and the background scattering ( empty holder ) was subtracted using the saxs_nt v4.1 program package ( bruker axs gmbh , karlsruhe , germany ) .", "answer": "abstractpolymeric polypyrrole and polythiophene solid phase microextraction ( spme ) coatings were prepared using electropolymerization with a linear sweep voltammetry technique . \n physicochemical properties were measured using different methods , in particular small angle x - ray scattering and scanning electron microscopy . by using innovative approaches for pore size measurement , we were able to calculate a maximum of the pore size range from 80 to 90 nm . additionally , film thicknesses measured from 90 to 150 m . using scanning electron microscopy \n , we describe the characteristics of polymer growth on the support surface.graphical abstract", "id": 671} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin 2012 , an estimated 790,000 women in the united states were diagnosed with cancer , of whom 10% were of reproductive age ( american cancer society , 2012 , schover , 2005 ) .\n[ nih surveillance ] ( national institute of health , 2010 , society of family planning , 2012 ) addressing the possibility of future pregnancy is an important aspect of survivorship and quality of life for patients undergoing cancer treatment , and several ways to preserve fertility during cancer therapy have been developed and studied ( letourneau et al . , 2012 ,\nas background , 49% of pregnancies in the united states are unintended and unplanned ( the alan guttmacher institute ( agi ) , 2013 ) .\npatients with medical co - morbidities , including those undergoing cancer treatment and/or surveillance , are among this group .\nit is estimated the incidence of malignancy and pregnancy is approximately 1:1000 ( pavlidis , 2002 , smith et al . , 2003 ) . although rare , pregnancy in the setting of cancer treatment may create clinical and ethical dilemmas , with potential increased risks for both the patient and gestation .\nthese dilemmas are further compounded when a pregnancy in this setting is unplanned . among women who have undergone or are currently undergoing cancer treatment\n, there is limited data regarding the rate of unintended pregnancy or patients ' impression of fertility .\nit has been previously reported that childhood cancer survivors between 15 and 30 years old were more likely to terminate a pregnancy compared to age - matched controls ( green et al . , 2002 ) .\na survey of female cancer patients revealed that 55% believed that they could not become pregnant after cancer treatment , and 45% of the same group denied using any contraception method ( patel et al . , 2009 ) .\nboth of the aforementioned studies support the notion that we could improve counseling in this patient population regarding fertility potential and contraception planning . in gynecologic cancer patients , women with early stage cancers may be eligible for fertility sparing treatment , and therefore may be at risk for unplanned pregnancy after therapy if contraception is not addressed as well ( mclaren and bates , 2012 ) . for this reason\n, we conducted a survey of current members of the society of gynecologic oncology ( sgo ) regarding reproductive counseling , practices , and experience with unplanned pregnancy in this population .\nafter obtaining approval from our institutional review board , a list of member email addresses was obtained from the sgo .\nan email statement of confidentiality with the questionnaire link was emailed to all listed members . following the initial e - mail , members received two additional follow - up e - mails , two and four weeks respectively , after the initial contact .\nthe survey remained open for responses for two weeks following the third , and final , reminder .\nsurvey monkey was utilized to create and administer a nineteen question survey regarding demographics , contraception counseling and use practices , referral patterns , and incidence of unplanned pregnancy .\ndemographic data queried were age , gender , region of country of current residence , medical specialty , level of training , description of clinical practice , and number of years caring for gynecologic oncology patients .\nquestions regarding consistency to which the provider addresses contraception and fertility concerns were answered using a likert - type scale ( i.e. , always , sometimes , rare , never , not applicable ) .\nthe remaining questions were answered using a yes / no or a multiple - choice format .\nthe multiple - choice questions specifically addressed the frequency of contraception methods counseling and administration , and number of patients experiencing unplanned pregnancy .\nparticipants were asked to check all contraceptive methods that they counseled and administered / prescribed .\ncontraceptive methods specifically included were the oral contraception pill ( ocp ) , injectable , intrauterine device ( iud ) , or subdermal levonorgestrel implant .\nprevalence of unplanned pregnancy was evaluated by asking practitioners to estimate prevalence of unplanned pregnancy among their patients ( during or after treatment ) in the previous one and five years respectively .\nwe excluded the responses of anyone who reported that he / she was retired or did not provide information on their reproductive counseling patterns .\nlogistic regression analysis was used to model separately the odds of always or sometimes offering fertility and/or contraceptive counseling .\nall analyses were conducted using stata 13.0 ( statacorp , college station , texas ) .\nquestionnaires were completed by 261 respondents , yielding a response rate of 18% . among the respondents 21 ( 8% ) reported that they were retired and/or did not provide information regarding their reproductive counseling patterns and thus were excluded from the analysis .\noverall , the respondents had a mean age of 47 years with a slight predominance of females ( 52% ) , which is consistent with sgo demographics ( mean age of male members 50 years old , mean age of female members 45 years old ) .\nour survey had a higher proportion of fellow respondents ( 24% ) than sgo as a whole ( 9% ) [ gynecologic oncology 2015 : state of the subspecialty ] selected characteristics of respondents are presented by reproductive counseling status in table 2 . among respondents ,\n34.6% reported sometimes or always providing counseling on fertility and contraception , 19.2% reported providing fertility counseling only , 15.8% reported providing contraception counseling only , while 30.4% reported not routinely providing counseling on either topic .\nin general , providers who reported providing reproductive counseling on neither topic were more likely to be male and/or a fellow .\nthey also tended to be < 40 years of age , though this difference was not statistically significant .\nphysicians who reported not routinely counseling on either topic were less likely to report prescribing or administering contraception and/or were less likely to report referring to reproductive endocrinology .\nin contrast , those who reported providing counseling on both fertility and contraception were more likely to be female and/or an attending .\nthey also were more likely to be older ; although that difference was not statistically significant . providers who reported sometimes or always providing counseling on both reproductive topics were also more likely to report providing or administering contraception and/or to refer to reproductive endocrinology . there were no notable differences in reproductive counseling status by u.s .\nnext , we examined what factors were associated with an increased odds of reporting providing fertility counseling sometimes or always ( table 3 ) .\nafter adjustment for gender , we found that the odds of reporting providing fertility counseling were nearly three times higher among attending physicians as compared to fellows [ aor = 2.72 ; 95% ci = ( 1.44 , 5.12 ) ] . in examining contraceptive counseling ( table 4 )\n, we found that the odds of reporting providing contraceptive counseling was 2.8 times higher in women as compared to men and was 4.91 times higher in individuals age 50 + compared to those < 40 after adjustment for level of practice .\noverall , 81.7% of providers reported counseling , prescribing , or administering contraception to their patients . among these individuals ,\nthe most frequently cited contraceptive that providers reported addressing with their patients included : oral contraceptive pills ( 81% ) , intrauterine devices ( 73% ) , depot medroxyprogesterone acetate ( dpma ) injections ( 56% ) , and contraceptive implants ( 21% ) .\nthe most frequently cited contraceptives that providers reported prescribing or administering included : oral contraceptive pills ( 80% ) , intrauterine devices ( 62% ) , dpma injections ( 48% ) , and contraceptive implants ( 9% ) .\nthe reported prevalence of unplanned pregnancy among the surveyed providers ' patients was relatively rare , perhaps because it is not routinely addressed .\nmost providers ( 95% ) reported 05 unplanned pregnancies among their patients in the last 5 years , with only 3 providers ( 1% ) reporting more than ten unplanned pregnancies .\nunplanned pregnancy in the setting of cancer treatment or surveillance is a complicated issue , and may create clinical and ethical dilemmas for the patient , partner , family , and treatment team .\nthe majority of survey respondents appropriately acknowledged the risk of unplanned pregnancy among gynecologic cancer patients maintaining fertility potential .\nhowever , only half reported addressing contraception planning in this population on a consistent basis ( 52% always addressing contraception , versus 35% sometimes ) . regarding the consistency with which contraception is addressed ,\nthese findings are consistent with a retrospective chart review completed at our institution where 45% of initial consultations documented a contraception plan in fertile patients of reproductive age , and 32% of follow - up visits for those that maintained fertility potential after cancer treatment ( crafton et al . , 2016 ) . depending on individual circumstances\npatient 's reproductive goals should be determined in order to tailor fertility - sparing treatment , when possible , versus contraception planning .\nunfortunately , only half of respondents reported always addressing fertility concerns with patients in this population .\nthis is consistent with the fact 59% of those surveyed routinely offer referral for preconception counseling for those patients considering fertility preservation options or planned pregnancy .\nreferral specifically for contraception counseling was reported less frequently , and even fewer reported follow up for plan establishment .\nour study was unable to determine which patients or providers relied on the patient 's primary care physician or gynecologist for the establishment of a contraception plan .\nthe incidence of unplanned pregnancy in this population is reportedly rare , with 96% of responding physicians experiencing < 5 unplanned pregnancies in the previous five years .\nthis may be under - reported , as oncologists may be unaware of pregnancies , especially during disease surveillance . despite the rarity ,\neleven providers report experiencing an estimated 620 unplanned pregnancies during that time same . the opportunity to avoid even a fraction of those merits further acknowledgement of this topic .\nit is reassuring that the large majority of providers reportedly counsel for and administer contraception methods , including 89% reportedly counseling for the iud and 77% employing its use .\nhowever , it was not specified in this survey if the indication for oral contraceptive pills ( ocps ) or an iud was for contraception planning or cancer therapeutic purposes . of reported methods ,\nocps were the most frequent contraception method both counseled for and administered . when compared to implantable methods , both the iud and subdermal implant , both actual and ideal use of ocps\nhave a higher failure rate , and therefore more reliable methods should be considered first , barring contraindications ( centers for disease control and prevention , 2010 ) .\ngiven our findings that the attending cohort was more likely to provide contraception and/or fertility counseling sometimes or always compared to the fellow respondents ( table 2 , table 3 ) , there seems to be an opportunity to improve education for fellows regarding fertility preservation options for these patients . as seen in other survey - based studies ,\nthe primary limitation of the study is the modest response rate , despite multiple recruitment attempts and limiting the length of the survey ( cunningham et al . , 2015 ) .\ngiven the response rate , the potential for selection and survey content bias ( i.e. , only those who were interested in the topic responded ) is present thus the results may have limited external validity .\nhowever , as aforementioned , our respondent cohort is comparable to the data published in the 2015 society of gynecologic oncology : state of the subspecialty .\ninclusion of both fellows in training and retired members also limits the external validity of the survey regarding current members , but we felt inclusions of these populations were interesting and important in order to compare potential generational differences .\nmany gynecologic cancer diagnoses are made in peri - menopausal or postmenopausal women ; therefore assessing what portion of a provider 's practice is of reproductive age could aid discussion and interpretation of results .\nlikewise , as the type of cancer and respective treatment options may change the potential for or etiology of infertility , assessing providers ' experience with specific disease processes , such as gestational trophoblastic neoplasia , also could aid discussion , and intervention .\nwe acknowledge that a contraception plan may not appropriate for all patients undergoing cancer care , especially for who decline fertility sparing treatment , have been previously sterilized , or are actively attempting conception / currently pregnant .\nhowever , routine recognition of reproductive goals should be addressed by providers to alleviate potential biases or assumptions regarding patients ' reproductive goals or sexual activity .\nprevious literature has reported providers ' lack of counseling and patients ' misunderstanding of reproductive potential after cancer treatment , and therefore a patient survey would be as valuable as the provider 's impression we report ( patel et al . , 2009 , karaoz et al . , 2010 ) .\nas life expectancy following cancer treatment diagnosis and treatment improves , and quality of life of survivors is emphasized , helping women meet their reproductive goals should remain an important focus .\ncomprehensive reproductive counseling should be emphasized , including both fertility sparing options and contraception planning , with the ultimate goal of decreasing unplanned pregnancy .", "answer": "we sought to identify how gynecologic oncologists approach reproductive counseling for their fertile , reproductive age patients , and their experience with unplanned pregnancies.members of the society of gynecologic oncology ( sgo ) were surveyed electronically regarding consistency of counseling patterns of contraception and fertility concerns , most and least common contraceptive methods utilized , referral patterns , and incidence of unplanned pregnancy . of the 1424 sgo members identified , 261 participated in the questionnaire , yielding a response rate of 18% . \n eighty - two percent of respondents agreed unplanned pregnancy is a potential problem , but only 57% believed their patients understood unplanned pregnancy is possible during treatment . \n half of respondents report always in terms of frequency that contraception is addressed among their high - risk patients . after adjustment for gender \n , we found that the odds of reporting providing fertility counseling were nearly three times higher among attendings as compared to fellows [ aor = 2.72 ; 95% ci = ( 1.44 , 5.12 ) , three times higher in women as compared to men [ aor = 2.80 ; 95% ci = ( 1.46 , 5.38 ) ] , as well as in individuals 50 + years as compared to those < 40 years old [ aor = 4.91 ; 95% ci = ( 2.05 , 11.74 ) ] . \n ninety - six percent reported < 5 unplanned pregnancies , to their knowledge , in the previous five years of clinical practice . \n most providers acknowledge that unplanned pregnancy is a potential risk in fertile gynecologic oncology patients , but only half believe their patients understand an unplanned pregnancy is possible . \n an opportunity exists to provide more directed counseling regarding fertility during and after cancer therapy , and to educate patients and providers regarding more reliable , long acting contraceptive methods .", "id": 672} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npsychiatric and psychological morbidity has been reported in patients with genital warts . even though , genital warts are generally not associated with severe symptoms , they have profound adverse impact on quality of life of patients .\nif patient with genital warts , complains of severe and unusual symptoms are often considered psychological .\nwe report a case of giant genital warts where the patient complained of formication ( insect - crawling sensation ) which was subsequently found to be due to maggot infestation in the warts .\na 23-year - old married woman presented with large exophytic growth arising from perineum , vulva , introitus of the vagina , and inner aspect of thighs for past 4 months [ figure 1a ] .\npatient developed severe itching and formication in the lesions for 1 week , though she had never seen or recovered any insect .\nsexual history of the patient and her husband was unremarkable . in view of giant genital wart\n, serum enzyme - linked immuno sorbent assay ( elisa ) for hiv and venereal disease research laboratory ( vdrl ) test for syphilis was done for both husband and the wife but were negative .\n( c ) three months after complete excision using a radiofrequency device cutaneous examination revealed an approximately 10 5 cm\nhyperpigmented , pedunculated growth with verrucous surface over both the labial folds symmetrically , completely obliterating the introitus . on per speculum examination ,\na diagnosis of giant condylomata acuminata was made and it was thought that patient 's unusual complaint about the \nthe hpv viral genotyping using linear array ( roche ) showed hpv 6 and 11 .\nhistopathology from the warts did not show any evidence of bushke lwenstein tumor or squamous cell carcinoma . on histopathological examination hyperkeratosis , papillomatosis , koilocytosis and dilated and congested\ncapillaries in the dermis were found . within few days of presentation , she started complaining of paroxysms of severe perineal scratching consequent to increased sensation of crawling insects . but\nthinking that the disease was causing immense psychological stress hence leading to the strange symptoms , serial excision of the warts with a radiofrequency device ( ellman , oceanside , ny , usa ) was planned . during the procedure ,\nlocal anaesthetic ( 2% lignocaine with adrenaline ) was infiltrated in the lesion and the procedure was started .\nsuddenly , perhaps due to irritation caused by radiofrequency current , multiple live maggots were seen coming out of verrucous masses [ figure 1b ] .\nthe procedure was abandoned and thick white petrolatum was applied to the area . approximately 20 live maggots were then removed with the help of forceps [ figure 2 ] and few of them were sent for entomological examination .\nthe patient was given intravenous antibiotics ( ceftriaxone and amikacin ) in view of some denuded area produced due to radiofrequency excision of few warts .\na magnetic resonance imaging ( mri ) of abdomen and pelvis was done to rule out deeper soft tissue infestation and damage by the maggots which turned out to be normal .\npatient 's symptoms completely resolved with few more sessions of extraction of maggots over the next 2 days and subsequent examination did not reveal any maggots .\nsome of the removed maggots later , external genital warts were completely excised with radiofrequency [ figure 1c ] .\nthere was no recurrence of excised warts in 4-month post - operative follow - up .\nwarts inside the vagina are being treated with imiquimod and at the time of writing this report , they have reduced substantially in size and this treatment is being continued .\nmyiasis is a parasitic infestation of human or animal skin , necrotic tissues and natural cavities by fly larvae or pupa .\nhuman myiasis is caused by fly larvae capable of penetrating body orifices as well as healthy or necrotic tissue .\npatton divided myiasis - causing flies into three parasitologic categories : obligatory , facultative , and accidental .\ncochliomyia hominivorax , chrysomya bezziana , and wohlfahrtia magnifica are the most common flies worldwide that cause human wound myiasis .\nchrysomia bezziana is the most common cause of cutaneous myiasis in india but usually infests wounds and mucous membranes .\npredisposing factors for human wound myiasis include open wounds , poor hygiene , advanced age , psychiatric illness , diabetes , vascular occlusive disease , and physical handicap .\nthe clinical manifestations of wound myiasis vary according to the affected body area and the extent of the infestation .\npatients may present with fever , pain , bleeding from the infested site or may be complicated by secondary infection and tetanus .\nas far as ascertained , there is only one report in literature on myiasis in genital warts from brazil in which the patient was pregnant and after removal of maggots the pregnancy ended in spontaneous abortion .\nmyiasis in our case was unusual in view of its site and its occurrence in the absence of the usual risk factors .\ndue to rarity of condition , and our unfamiliarity we did not consider infestation by maggots though patient complained of crawling sensation and severe itching in the genital warts . the lesson learnt is to examine and investigate the patient thoroughly before dismissing patient 's complaints as irrelevant , psychogenic or functional , however unusual and unexplainable they are for the disease .\nthe simplest treatment for myiasis is application of an occlusive agent such as white soft paraffin , wax , glue , adhesive tape or chewing gum followed by physical removal of maggots .", "answer": "a 23-year - old woman presented with large exophytic genital wart arising from perineum , vulva , introitus of the vagina , and inner aspect of thighs . \n patient developed severe itching and formication ( insect - crawling sensation ) in the lesions for past 1 week , though careful examination did not reveal any insects . considering that the disease was causing psychological stress and physical symptoms , radiofrequency excision was planned . \n however , during the procedure , several maggots appeared from the crypts . \n the procedure was abandoned and maggots were removed manually . subsequently external giant warts were removed using radiofrequency device . \n there was no recurrence of excised warts during 3 month follow - up . \n to our knowledge , this is the second reported case of maggots in genital warts .", "id": 673} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a recent article in genome research , thompson and colleagues present a development of a next - generation sequencing technology - the heliscope sequencer - that enabled them to detect mutations in the human breast cancer 1 ( brca1 ) gene , as a model of a clinical diagnostic protocol .\nit therefore holds great promise for overcoming the emerging problem in clinical genetics of target overload : the presence of a large number of gene mutations of clinical relevance in a single disease entity . in no field is this challenge more apparent than in the genomics of cancer .\nthe past few years have seen an unprecedented deluge of data on the genes mutated in cancer and other diseases . so far , the sequences of over 50 individual cancer genomes have been published and this number is set to increase exponentially .\nthe advent of next - generation technologies ( such as the roche 454 gs flx+ , llumina hiseq 2000 , applied biosystems solid and heliscope single - molecule sequencer machines ) , which allow a human genome to be sequenced in a single week - long run , has led to a large shift in our understanding of the mutations that drive cancers . for the clinician , mutations in cancer can have relevance for diagnosis , prognosis and treatment choice .\nhowever , it is now apparent that these clinically relevant mutations will be both numerous and found at low prevalence in individual cancer types . in particular , for the majority of cancers there will be no single ' magic bullet ' targeted therapy .\nthe breakpoint cluster region - abelson murine leukemia homolog ( bcr - abl ) fusion kinase , which is characteristic of chronic myeloid leukemia , is the exception not the rule when it comes to druggable cancer genes ; it seems , instead , that multiple drug targets will be mutated at low frequency throughout common cancers .\nthis target overload is not restricted to the management of cancers and is also seen with monogenic disorders , for example , mental retardation and hereditary cancer pre - disposition .\nit is therefore necessary to screen numerous genetic loci to decide on the best course of clinical management for an individual patient and this must be done in a rapid and cost - effective manner .\nthe current technology for searching for mutations is to amplify a region of interest - in multiple fragments of a few hundred base pairs each in separate pcr reactions - then sequence the products by standard sanger chain terminator sequencing . although highly accurate for the detection of single - nucleotide variants and small insertions or deletions , this approach is expensive , labor intensive and unable to detect large - scale insertions or deletions .\nthis is because sanger sequencing can reliably detect mutant alleles only when they are present in more than about 20% of the relevant dna , and this will not be the case , for example , for a heterozygous mutation in a tumor contaminated with 60% normal dna , a scenario that is not uncommon .\nthompson and colleagues have used a next - generation true single - molecule sequencing ( tsms ) system , the heliscope sequencer , to profile the mutational pattern of the human cancer gene brca1 .\ngermline mutations in the genes brca1 and brca2 are associated with dramatically increased rates of breast and ovarian cancers and contribute to about 10% of all breast cancer cases .\nin addition , poly - adp ribose polymerase inhibitors , a recently developed family of pharmaceutical agents , seem to show selective toxicity for cancers with mutations in the brca genes . cost - effective sequencing of these genes is therefore a highly desirable clinical tool for the management of breast cancer patients and those with strong family histories of the disease .\nthe technology used is a development of the heliscope tsms platform . in the standard heliscope protocol\n, dna is fragmented and poly(a ) adaptors are added to the ends of fragments .\nthey are then captured on a glass slide coated with covalently bound poly(dt ) oligonucleotides , and sequenced .\nthompson et al . were able to dispense with the initial sample preparation steps ( addition of poly(a ) adaptors and 3 ' blocking - performed to prevent extension of the 3 ' end of bound poly(a)-tagged dna molecules ) and instead directly captured only the fragments of dna belonging to the brca1 locus , using oligonucleotides that match sequences in the brca1 region ( figure 1 ) .\napproximately 20% of the sequenced reads mapped to brca1 , which equates to about 100,000-fold enrichment of the target sequence . as the length of sequence that can be read in this system\nis limited , oligonucleotides were designed at 20 - 30 base pair intervals throughout the coding sequence of the gene , to ensure complete coverage .\nimportantly , the authors were able to obtain sequencing results from as little as 100 ng of input material - thus showing that the technology could be used with samples collected as diagnostic biopsies .\ntumor material can be collected and ( a ) snap frozen to preserve intact dna and rna or ( b ) fixed in formalin then embedded in paraffin for section and histopathological review . following ( c ) dna extraction , ( d ) the dna\n( e ) dna fragments are hybridized to the flow cell , which is covered with oligonucleotides with sequence complementary to the region corresponding to the brca1 gene .\n( f ) each individual molecule of dna is then sequenced simultaneously by sequential addition of fluorescently labeled nucleotides ( purple ) .\nthis approach has several advantages over the more traditional sanger sequencing commonly used for the detection of mutations .\nfirstly , there is little required in the way of sample preparation - only sonication of the dna , and in the case of archival formalin - fixed material it is possible that even this step could be dispensed with - therefore reducing cost , turn - around time and the risk of errors in sample handling . secondly ,\nunlike sanger sequencing , the heliscope system allows the detection of large deletions , by determining the number of fragments of dna that are present from a specific location ; a decreased number of fragments from a region suggests a loss of genetic material .\nfinally , the heliscope system directly sequences individual molecules rather than - as with sanger sequencing - examining the average sequence of many millions of dna molecules .\nthis should provide increased sensitivity for the detection of low prevalence mutations , an essential feature in the sequencing of a heterogeneous cancer sample .\nthe present technology is an advance over recently presented techniques for analyzing the mutational status of target genes using next - generation sequencing instruments . with the advent of more competitively priced next - generation sequencing machines , which can provide sequence data in a matter of hours , not days ( such as life technologies ' ion - torrent and illumina 's miseq ) , it is feasible that such approaches could be used routinely in the clinical setting .\nhowever , the instruments involved still require the selective amplification of target dna and the relatively complex preparation of this material for sequencing .\nthus , although they take advantage of the exceptionally cheap per - base cost of next - generation sequencing , competing techniques are still limited by its flaws : high complexity and slow turnaround time . genotyping by mass spectrometry has also been applied to the resequencing of relevant mutations . this approach , although sensitive , is limited , in that it is capable of detecting only known mutations and will therefore miss novel gene lesions .\nfor the foreseeable future , the high cost and complexity of data analysis will limit the application of whole - genome sequencing for the detection of mutations in a clinical setting .\ntargeted resequencing of areas of interest will therefore remain key to determining mutational status . the method published by thompson et al . \nalthough currently only a single gene is screened , there is clearly scope for the creation of multi - gene capture arrays , allowing large numbers of loci to be analyzed rapidly and cost - effectively with low dna input requirements . in its simplicity\n, this approach provides an opportunity to truly begin integrating the vast quantity of genomic data generated in this next - generation era with clinical practice .\nwe would like to thank claire pike and karen howarth for helpful discussion and reading of the manuscript and the wellcome trust translational medicine and therapeutics program , breast cancer campaign and cancer research uk for funding .", "answer": "in many fields it is now desirable to sequence large panels of genes for mutation , to aid management of patients . \n the need for extensive sample preparation means that current approaches for assessing mutation status in the clinical setting are limited . \n a recent publication demonstrates a single - step , targeted , true single - molecule sequencing approach to assessing the mutational status of brca1 . \n fragmented dna samples are loaded directly onto a flow cell and sequenced , thus detecting both small- and large - scale mutations with minimal sample preparation and high accuracy .", "id": 674} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin february 2007 , the board and the assembly of deans of medical schools of the dutch federation of university medical centres decided to institute a project group to revise the 2001 medical education blueprint .\nthe main reasons for undertaking this project were developments in medical scientific disciplines , such as biotechnology and genetics , and developments in medical education , such as the introduction of the bachelor - master structure and the ongoing modernization of postgraduate speciality training programmes . in revising the 2001 blueprint\nthe project group was specifically asked to establish the attainment levels of both the bachelor and the master programme in medicine , to consider whether the canmeds model or a similar competency profile could also be serviceable in revising the new framework for medical education and to reconsider the level of detail of the revised 2001 blueprint , aiming to find formulations that are realistic and testable and that facilitate external accountability for programme content .\nframework was thought to reflect bettter the nature of the document ) . on august 12 , 2009 ,\nthe 2009 framework for undergraduate medical education in the netherlands was presented to the dutch minister for health .\na translation in english is available from the website of the dutch federation of university medical centres ( http://www.nfu.nl/fileadmin/documents/raamplan2009engelstalige_versie.pdf ) .\nthe 2009 framework consists of nine chapters : introductionexplanationdevelopments in dutch and european legislationstages , cycles and levels in medical education in the netherlandsmaster s degree programme in medicine : target profilemaster s degree programme in medicine : competenciesmaster s degree programme in medicine : issues relating to illness and healthbachelor s degree programme in medicine : profile and learning outcomesbasic sciences in the medical curriculum developments in dutch and european legislation stages , cycles and levels in medical education in the netherlands master s degree programme in medicine : target profile master s degree programme in medicine : competencies master s degree programme in medicine : issues relating to illness and health bachelor s degree programme in medicine : profile and learning outcomes basic sciences in the medical curriculum in an appendix the final document also includes a skills list .\nin 2002 , the bachelor - master structure was introduced in the dutch system for higher education , establishing bachelor s degree and master s degree programmes as independent study programmes .\nthis change followed in the wake of the signing of the bologna declaration in 1999 .\nthis declaration , signed by 29 european countries , aims to promote greater overall convergence in higher education in europe , based on a two - cycle degree structure . in the transitional period ,\npermission to use the protected title of physician and qualification to perform certain actions reserved for physicians are linked to registration in the individual health care professions act register .\nregistration is only open to those who have completed the degree programme in medicine and therefore to those who , following the introduction of the bachelor - master structure , have obtained the master of science ( msc ) degree on completion of the master s degree programme in medicine .\nthe project group decided to define students learning outcomes upon completion of the master s degree programme in terms of competencies .\na competency is defined as the ability to adequately perform a professional activity in a specific , authentic context , using an integrated body of knowledge , understanding , skills and professional behaviour .\nafter careful consideration , the canmeds model was chosen , because , firstly , this model involves an excellent and useful division into physicians roles and competencies in a variety of professional situations , and secondly , this model is also used in the framework of the modernization of postgraduate specialty training .\ntogether , the seven roles or competency domains in the canmeds model constitute the target profile in chapter 5 of the 2009 framework ( see table 1 ( tab .\nthe profile is elaborated in terms of key competencies and their constituent sub - competencies .\nas the project group felt that bachelor students in medicine do not yet operate in an authentic professional setting , the bachelor s degree programme is described in terms of knowledge , skills , and behaviour and not competencies .\nknowledge and understanding relate to the basic sciences , the foundation of medicine in the natural sciences , and aspects of behavioural and social sciences .\nthe 2001 blueprint included a list of clinical conditions which comprised about 330 clinical conditions in all .\nissues relating to illness and health was more appropriate to the wide - ranging field in which today s physicians are operating , as a fair share of physicians work is not directly patient or disease related . the list of issues described in chapter 7 has been subdivided into several categories .\nthe first and most voluminous one comprises the complaints that induce patients to consult their physician .\nthe next two , smaller , categories deal with findings upon physical and additional examinations .\nthe introduction of a list of issues meant that the list of clinical conditions that was included in the 2001 blueprint was not to return in the 2009 framework : on the one hand , the contemplation of each issue would involve a series of clinical presentations anyway , and , on the other hand , a list of clinical conditions would require ceaseless maintenance in the wake of ongoing developments in medical disciplines . in the 1994 blueprint and the 2001 blueprint ,\nthe project group felt that the aspect of required knowledge had been somewhat eclipsed by lists of problems , clinical conditions and skills .\nright from the start , the project group wished to give the basic sciences a more prominent place in medical education .\nthe model of competencies selected by the project group also carried the risk of outlining required knowledge only implicitly .\ntherefore , in the 2009 framework , a separate chapter is devoted to basic sciences in the medical curriculum dealing with both the foundation of medicine in the natural sciences and aspects of the behavioural and social sciences .\nspot - checking at the eight dutch medical faculties showed that all medical faculties still used this list , sometimes with minor adjustments .\nafter discussion in the project group , the skills list from the previous blueprint , with minor adjustments , was added to the appendices to the 2009 framework .\nthe project group was asked to pay special attention to finding formulations that are realistic and testable and that allow external accountability for medical education programme content .\nthis prompted the project group to clearly define the competencies in terms of levels that are to be attained . \nmedical education in the netherlands involves a training sequence with two stages that medical students pass through in succession .\nthe first stage of this training sequence comprises two cycles : a three - year bachelor s degree programme in medicine , followed by a three - year master s degree programme in medicine . in the second stage of the training sequence , following upon completion of the bachelor and master programmes ,\nmedical graduates undertake postgraduate specialist training to become medical specialists in primary or secondary healthcare .\nhaving completed that stage , medical practitioners then engage in lifelong learning activities both in practice and in formal continuing education courses .\nthe levels linked to the successive stages can be called starter level , beginning practitioner level and experienced practitioner level . after completion of their bachelor programme in medicine , medical students can be characterized as starters .\nthese students have mastered a basic body of knowledge and understanding of scientific disciplines that are relevant to their subsequent professional practice .\nthey have also acquired a set of basic skills and are able to show appropriate professional behaviour in training - related situations .\nthey are able to apply knowledge , skills and behaviour in dealing with issues that involve a relatively low level of complexity .\nafter completion of the master programme in medicine , medical graduates can be characterized as beginning practitioners .\nnewly graduated physicians demonstrate a basic competence in practice , possess an integrated body of knowledge , skills and professional behaviour and can handle issues involving higher levels of complexity .\nmedical graduates are capable of performing independent consultations but only perform these under supervision during postgraduate medical training . after a number of subsequent years of further schooling , training and experience in medical specialist training in the discipline of their choice , physicians operate independently without supervision .\nan element of independent practice is participation in interprofessional coaching activities and lifelong continuing - education courses . in the 2009 framework ,\nthe levels of proficiency to be achieved in the bachelor and master programmes in medicine are defined in a five - level structure ( see table 2 ( tab .\nthe project group also had to consider the level of difficulty of the issues that are presented to students .\non the one hand , these are medical factors , such as typical and atypical presentations or co - morbidity problems ; on the other hand , these are contextual factors from the psychosocial model . the level of difficulty is then codetermined by the availability of standard solutions to a problem and the applicability of protocols and guidelines .\nthe level of difficulty also lies in the degree to which different physician roles must be integrated in dealing with the issue in question .\ngraduates in medicine must be able to handle issues involving varying - including higher - levels of difficulty , with the proviso that the degree of required supervision increases with the degree of difficulty of the case presented . in this respect ,\nthere is one sub - competency incorporated in the role of medical expert that is of particular importance : students ability to recognize and name the personal limits to their knowledge and skills and to decide in time if , and , if so , when a third party needs to be called in , including their supervisor .\nthe 2009 framework states that graduates in medicine must have mastered all issues related to illness and health that are included in the list at least at level ii .\nsome of the issues , depending on the specifics of individual training programmes , will be included in additional competency testing at higher levels .\nthe formulations of sub - competencies specify the levels ( iii , iv , or v ) that have to be attained .\nto illustrate the assignment of levels some examples are given in table 3 ( tab .\nmajor changes are the definition of competencies , the indication of the levels of competency to be attained and the introduction of a list of issues related to health and disease .\nthe 2009 framework will be used as the basis for accreditation and for a revision of the legislation that outlines the educational requirements of physicians .\nlaan , md phd , is professor of rheumatology and medical education , radboud university medical centre , institute for medical education , nijmegen , the netherlands.r.r.m .\nleunissen , msc , is senior staff member , radboud university medical centre , institute for medical education , nijmegen , the netherlands.c.l.a .\nvan herwaarden , md phd , is professor of pulmonology and former dean of the radboud university medical centre , nijmegen , the netherlands .\nlaan , md phd , is professor of rheumatology and medical education , radboud university medical centre , institute for medical education , nijmegen , the netherlands .\nleunissen , msc , is senior staff member , radboud university medical centre , institute for medical education , nijmegen , the netherlands .\nvan herwaarden , md phd , is professor of pulmonology and former dean of the radboud university medical centre , nijmegen , the netherlands .", "answer": "the 2009 framework defines the joint dutch national learning outcomes to be attained by medical students after completing their three - year master programme in medicine . \n the framework thus helps to guarantee to society at large and to patients in particular that medical graduates who are starting out as practitioners have attained a certain professional level . \n this level is the aggregate of the physicians target profile , physicians ( sub- ) competencies to be achieved and the list of issues relating to illness and health . \n in addition , the framework also defines the profile of the bachelor and the learning outcomes of the bachelor programme in medicine .", "id": 675} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nscreening for gestational diabetes mellitus is routinely programmed to prevent complications caused by elevated blood glucose levels in pregnancy , including macrosomia , cesarean delivery , shoulder dystocia , neonatal metabolic problems , perinatal mortality , and pre - eclampsia.1 diabetes mellitus during pregnancy also appears to be associated with an increased risk of cardiovascular diseases even in later life.2 moreover , this underlying co - morbidity is an independent risk factor for subsequent coronary artery disease . in this context ,\ndiabetes mellitus during pregnancy has been identified as a major etiology for atherosclerosis in large elastic arteries.3 one of the main indicators for assessing atherosclerotic lesions during this period is the increased intima - media thickness ( imt ) of carotid arteries.4 it has been well known that , as opposed to the blood flow through the other arteries of the maternal organs , the blood flow through the carotid artery is decreased during pregnancy , which has been attributed to pregnancy - mediated increased responsiveness of the carotid artery to vasoconstrictors and decreased responsiveness to vasodilators.5 also , the endothelial hypertrophy of the carotid artery can be a common finding , leading to changes in the carotid blood flow and its complications.6 , 7 thus , increased carotid imt can be deemed a validated endothelial dysfunction surrogate endpoint during pregnancy .\nsome studies have recently shown that pregnant women with previous gestational diabetes mellitus are at increased risk of carotid artery disorders.8 , 9 be that as it may , the scarcity of research into this hypothesis means that it is still unknown whether or not gestational diabetes mellitus causes increased imt .\nthe current study was performed to evaluate carotid imt in diabetic pregnant women with gestational diabetes and to ascertain if an impaired oral glucose challenge test ( ogct ) correlates with the development of increased imt .\nthis cohort study included 50 women ranging from 18 to 35 years of age at high risk of diabetes during pregnancy .\ngestational diabetes mellitus was screened with a one - hour 50 g oral glucose challenge test ( ogct ) .\nabnormal results were , thereafter , confirmed with a three - hour 100 g oral glucose tolerance test ( ogtt ) .\neligible women were nulliparous with a singleton pregnancy , had a normal blood pressure at the time of recruitment , and gave informed consent .\nwomen with any of the following were excluded : family history of cardiovascular disorders ; history of hypertension ; anti - hypertensive and cholesterol medication use ; hyperlipidemia ; overt diabetes or fasting plasma glucose ( fpg ) > 125 mg / dl according to the american diabetes association ( ada ) definition;10 chronic renal or hepatic diseases ; malignancies ; recent hormonal medications ; cigarette smoking ; severe obesity ( body mass index [ bmi ] > 35 kg / m ) ; and history of infertility or polycystic ovarian disease .\nthose with the status of plaques / shadowing ( > 1.0 mm ) at any carotid site were also excluded .\nthe study protocol was approved by the research and ethics committees at kerman university of medical sciences .\nbaseline demographic variables were collected either from the women s medical records or self - completed questionnaires at trial entry and comprised maternal age , height , weight , bmi , smoking status , and blood pressure at trial entry .\ntotal cholesterol was measured enzymatically with standard methods and total triglyceride was measured via standard spectrophotometric techniques . after the precipitation of low - density lipoprotein ( ldl ) particle with phosphotungstic acid , high - density lipoprotein ( hdl ) cholesterol was measured enzymatically in the supernatant by a modification of the method for total cholesterol .\nb - mode ultrasound scans were performed at baseline and at two time points of mid - term pregnancy ( 20 to 24 weeks ) and full - term pregnancy ( 36 to 38 weeks ) on all the participants .\ncarotid ultrasound scans were carried out by a single trained sonographer unaware of the study protocols and methodology .\nb - mode ultrasound images were equipped with a 7.5-mhz linear array transducer and captured with a ge log 200 ultrasound machine .\nthe ultrasonic variable used in the statistical analysis was the mean of the imt of common carotids and internal carotid arteries from two walls ( near and far walls ) at four different angles .\nthe mean of carotid imt was compared between the women with impaired ogct and those who screened normal on ogct at the two study time points . for the statistical analyses , the statistical software spss version 19.0 for windows ( spss inc .\nthe continuous variables , if normally distributed , were analyzed using the student - test and presented as mean differences , while the mann - whitney test was employed for skewed data .\nthe baseline characteristics of the pregnant women with impaired and normal ogct tests are presented in table 1 .\nthe two groups were similar in terms of pregnancy age , height , weight , bmi , and baseline laboratory parameters .\nthere were no significant associations between carotid imt and maternal indices , including the demographic variables and laboratory parameters .\nan overall comparison between the impaired ogct test group and the control group via the mann - whitney u test revealed significant differences in carotid imt in the midterm and full - term pregnancy ( table 2 ) .\nthe trend of the changes in carotid imt during the mid - term to full - term pregnancy was , however , insignificant in each group .\nan increased carotid imt can be observed not only in long - standing type ii diabetic but also in newly detected type ii diabetic patients . especially in pregnant women , carotid imt gradually increases from the first to the third trimester of normal pregnancy and regresses in the postpartum period .\nnevertheless , the trend of the increase in pregnant women with gestational diabetes is still unclear . in our study , with the aid of carotid ultrasound , arterial examination was performed at mid - term and full - term pregnancy and both controls and the women with an impaired ogct test were assessed and compared with regard to the changes in carotid imt .\nwe showed that although carotid imt was more increased in those with impaired ogct , the trend of this change was similar between the impaired and normal ogct groups .\nfurthermore , we observed that carotid imt was significantly higher in the diabetic group than in the normoglycemic group in different trimesters , but the trend of these gradual changes from the first to the third trimester was similar in both groups .\ntotally , effective glycemic control seems to be helpful for the prevention of increased carotid imt . during the pregnancy period ,\nperipheral vascular resistance is physiologically paralleled by improved macrovascular compliance.11 , 12 some researchers have shown that 2 - 4 years after previous gestational diabetes mellitus , a significantly higher arterial stiffness can be found compared with reference women without a history of diabetes.13 pregnancies complicated by diabetes not only are associated with increased carotid imt but also can lead to increased maternal arterial stiffness.9 this study demonstrates increased imt of the carotid artery in a group of women who had a pregnancy complicated by impaired ogct .\nthis finding is in line with the literature confirming that women with a history of gestational diabetes have a higher risk of developing increased carotid imt .\none of the first steps in the development of atherosclerosis is endothelial activation , followed by endothelial dysfunction .\nthus , in diabetes mellitus , vascular endothelial activation or dysfunction is considered to play a key role in the development of many of the clinical manifestations related to carotid artery disease , several years after delivery .\nsome epidemiological studies have found positive associations between parity and risk of carotid artery plaques in elderly women and , therefore , age of pregnancy can be a trigger for this phenomenon.14 also , multi - gravidity and previous history of coronary diseases have been also identified to be related to the appearance of carotid artery plaques.15 folate deficiency during pregnancy is another probable triggering factor for progressing carotid imt .\nfolate deficiency is linked with hyperhomocystinemia,16 which is associated with accelerated progression of atherosclerosis17 and , thereby , carotid artery imt .\npregnancy is potentially a cause of folate deficiency.18 consequently , it is possible that multiparous women are at risk of prolonged folate deficiency ; this may explain their susceptibility to the development of carotid artery imt .\nin the present study , the main limitation was blood glucose controlled by insulin ; we could not hold treatment because of ethical issues .\nalso , we did not assess the confounding effects of the triggering variables such as age of pregnancy , multi - parity , or medication during this period on increasing carotid imt ; that should be considered in further studies .\nprospective follow - up studies will also be needed and have meanwhile been started to determine whether diabetes during pregnancy itself is responsible for the increase in imt .\nin conclusion , an impaired ogct test is proven to be an independent risk factor for increased carotid imt and subsequent coronary artery disease .\neven with this small study , we were able to find an increased imt after diabetes appearance , which might be used as an indicator of a potential increased vascular risk .\nfurthermore , imt measurements in diabetic pregnant women could offer an opportunity to identify a high - risk group of women who might benefit from early screening and preventive measures .\nthese measures could include lifestyle interventions such as improving diet and physical activity as well as increased surveillance of blood pressure , serum lipids , and particularly blood glucose .", "answer": "background : pregnant women with previous gestational diabetes mellitus are at increased risk of progressive carotid artery disorders . \n the current study evaluated carotid intima - media thickness ( imt ) in pregnant women with gestational diabetes at two time points of mid - term and full - term pregnancy to determine whether gestational diabetes mellitus causes increased imt.methods:this cross - sectional study carried out at afzalipour hospital ( kerman , iran ) between 2009 and 2010 , recruited 50 women who were at high risk of gestational diabetes during pregnancy and had an oral glucose challenge test ( ogct ) as screening for gestational diabetes . \n b - mode ultrasound scans were performed at baseline and at two time points of mid - term pregnancy ( 20 to 24 weeks ) and full - term pregnancy ( 36 to 38 weeks ) on all the participants . \n the mean imt of common carotids and internal carotid arteries from two walls ( near and far walls ) at four different angles was assessed.results:an overall comparison between the impaired ogct test group and the control group revealed significant differences in carotid imt in the mid - term ( 0.65 0.07 vs. 0.59 0.06 mm ; p value = 0.002 ) and full - term ( 0.65 0.05 vs. 0.59 0.04 mm ; p value \n < 0.001 ) pregnancy ; however , the trend of the changes in carotid imt during mid to full - term pregnancy was insignificant in each group ( p value > 0.05).conclusion : carotid imt was significantly higher in the women with gestational diabetes than that in the normoglycemic group in different trimesters . \n this finding denotes that atherosclerosis might start years before the diagnosis of gestational diabetes in vulnerable women .", "id": 676} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nganglioside may influence growth and cell - to - cell interactions may be of importance in the development of malignancy . in the present study , we used a transplantable murine hepatoma as the experimental model , and treated the animals with 5-fluorouracil ( 5-fu ) as the active therapeutic drug to determine the membrane glycolipids content variety .\nkunming mice ( normal mice ) were obtained from the animal center at fu - dan university shanghai medical college .\nmice containing the ascites - form transplantable hepatoma were obtained from the cancer institute of jiangsu province .\nthe ascites was drawn from the transplantable hepatoma mice by a sterilized injector and placed into bacteria - free 0.9% nacl for dilution ( 1/3 , v / v ) .\nsubsequently , the normal mice were inoculated with 0.2 ml of diluted cells under the skin in the foreleg and armpit regions .\nthe tumors were allowed to grow for 13 days . usually , solid tumors weighing 12 g were found afterwards .\nthe animals were injected with 5-fu ( 0.2 mg/0.2 ml / day ) i.p . at 48 h after tumor cell transplant . in the control group\nthe animals were injected with a sterilized solution of 0.2 ml of 0.9% nacl instead of 5-fu .\na third group of animals , raised without hepatoma transplant or any other form of treatment , was used as the normal group .\nafter the administration of 5-fu or saline , the animals were sacrificed , and tissue and blood samples were collected for examination . based on the method of sevenerholom , the contents of ganglioside , tsa lsa , and r - sa were determined .\none - way anova was conducted to compare the biochemistry index of membrane glycolipids between the 2 groups .\nkunming mice ( normal mice ) were obtained from the animal center at fu - dan university shanghai medical college .\nmice containing the ascites - form transplantable hepatoma were obtained from the cancer institute of jiangsu province .\nthe ascites was drawn from the transplantable hepatoma mice by a sterilized injector and placed into bacteria - free 0.9% nacl for dilution ( 1/3 , v / v ) .\nsubsequently , the normal mice were inoculated with 0.2 ml of diluted cells under the skin in the foreleg and armpit regions .\nthe tumors were allowed to grow for 13 days . usually , solid tumors weighing 12 g were found afterwards .\nthe animals were injected with 5-fu ( 0.2 mg/0.2 ml / day ) i.p . at 48 h after tumor cell transplant . in the control group\nthe animals were injected with a sterilized solution of 0.2 ml of 0.9% nacl instead of 5-fu .\na third group of animals , raised without hepatoma transplant or any other form of treatment , was used as the normal group . after the administration of 5-fu or saline , the animals were sacrificed , and tissue and blood samples were collected for examination .\nbased on the method of sevenerholom , the contents of ganglioside , tsa lsa , and r - sa were determined .\none - way anova was conducted to compare the biochemistry index of membrane glycolipids between the 2 groups .\nin evaluating the ability of antimetabolic drug 5-fu to inhibit tumor growth , we found that the weight of tumors was significantly different between the 2 groups ( p<0.05 ) ( table 1 ) .\nganglioside content in hepatoma tissue was significantly different among the 3 groups ( p<0.01 ) , and those in the therapeutic group were significantly lower than in the control group ( p<0.01 ) . in the plasma of the hepatoma mice ,\nthe tsa and lsa contents were higher in in the control group than in the normal group ( p<0.05 ) , but the tsa and lsa content in the therapeutic group was lower than in the control group ( table 3 ) .\nthe tsa and lsa contents in the plasma of the hepatoma mice were higher in the control group than in the therapeutic and normal groups ( p<0.05 ) .\nno significant difference was found in the r - sa between the therapeutic and control groups .\npercent inhibition was calculated from the following equation : [ ( tumor weight of control group tumor weight of the therapeutic group)/tumor weight of the control group ] 100% . * * p<0.05 . to observe the ability of antimetabolism drug 5-fu in the inhibition of tumor growth\nare showed in table 4 , the transplanted hepatoma group weight of tumor was significance higher than that of normal control group ( p<0.05 ) .\ntherapeutic group , control group and normal group membrane content variety the ganglioside content in hepatoma tissue from the control group was significantly higher than that in normal mouse liver ( p<0.01 ) , whereas those in the therapeutic group was significantly lower than in the control group ( p<0.01 ) . in the plasma of the hepatoma mouse ,\nthe tsa and lsa content was significantly higher in the control group than the normal group ( p<0.05 ) , and the therapeutic group was significantly lower than the control group ( table 6 ) .\nthe ability to produce transplantable hepatoma and the effect of 5-fluorouracil ( 5-fu ) in the inhibition of tumor growth are depicted in table 4 .\nour data reconfirm the ability of 5-fu to inhibit the proliferation of tumor cells by competitive inhibition of the synthesis of thymidine monophosphate .\nthe mechanism could involve sialic acid , a family of acylated derivatives of neuragmic acid , which usually occurs as a terminal component at the nonreducing end of carbohydrate chains of glycolipids .\ncell surface and membrane components play a vital role in neoplastic behavior . increasing concentrations of sialic acid are common on the tumor cell surfaces of neoplasms .\nthe carbohydrate moiety may have an influence on growth , as well as cell - to - cell interaction and the development of malignancy .\nthe biochemistry index of membrane glycolipids may be considered as an ancillary indicator for judging therapy effect in transplanted hepatomas in mice .", "answer": "backgroundthe aim of this study was to investigate the variety of plasma contents of membrane glycolipids in 65 gastrointestinal tumors and 31 transplant hepatomas in mice.material/methodsthe experimental model was a transplantable murine hepatoma . \n experimental mice were divided into 3 groups.resultsthe lsa and tsa content in the 2 groups were significantly difference ( p<0.01 ) , and were significantly lower in the therapeutic group than in the control group ( p<0.01).conclusionsthese results indicate that membrane glycolipids index lsa and tsa are sensitive markers in gastrointestinal tumors . in the transplanted hepatomas in mice , they may be considered as ancillary indicators for judging the therapeutic effect of hepatoma .", "id": 677} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nceliac artery aneurysm is a quite uncommon vascular lesion , accounting for 5.1% of all splanchnic artery aneurysms . although rare , celiac artery aneurysm carries a definite risk for rupture and other complications .\nhowever , because of its rarity , no strong consensus concerning indications for intervention of asymptomatic celiac artery aneurysm exists in the literature . due to more frequent use of cross - sectional imaging , the dilemma of choosing the appropriate therapeutic option has become increasingly more important .\nherein , we present a case of an un - ruptured celiac artery aneurysm that was treated by surgical repair and also discuss the appropriate therapeutic strategy based on a literature review .\na 72-year - old female visited our department with complaints of fever and general fatigue .\nthe patient s medical history included type 2 diabetes mellitus with poor control and hypertension .\narrival revealed that her blood pressure was 147/62 mmhg , heart rate was 104 beats / min with regular rhythm , blood oxygen saturation was 95% under atmospheric conditions , and body temperature was 38.7 c .\nblood analyses revealed 11,260 white blood cells/l with 80.6% neutrophils and 0.69 mg / dl c - reactive protein ) ; mild hypoalbuminemia ( 3.3 g / dl ) ; coagulant dysfunction ( fibrin / fibrinogen degradation products ; 7 g / dl fibrinogen ; and 2.1 g / ml d - dimer ) , and severely impaired glucose tolerance ( 157 mg / dl and 11.2% hemoglobin a1c ) .\nshe weighed 52.4 kg , was 150 cm tall , and had a body mass index was 23.3 kg / m . inspection of the palpebral conjunctiva revealed no evidence of anemia .\nchest auscultation revealed no signs of abnormal heart murmurs and no rales or other abnormal respiratory sounds .\nthe abdomen was slightly distended and her peristalsis was normal ; no tenderness was observed in the upper abdomen .\nshe was then diagnosed with bacteremia by urinary tract infection and antibacterial medicine ( cefmetazole 2 g per day ) was initiated .\ntransesophageal echocardiography was performed to investigate infective endocarditis , revealing no vegetation at her valves .\ncontrast - enhanced computed tomography ( ct ) was performed for investigating her urological abnormalities , revealing no urological deformities but a 28 30 mm sized aneurysm at the trunk of the celiac artery ( fig .\nthe proper hepatic artery was dominantly supplied from the celiac artery , the left gastric artery being bifurcated from the celiac trunk , and the celiac artery and the splenic and common hepatic artery had a common trunk ( fig .\nsurgical repair of the aneurysm was performed after confirmation of negative blood culture for bacteria on day 32 .\nfirstly , lesser omentum and crus of diaphragm were incised to expose abdomen aorta at the level of the trunk of the celiac artery .\nafter that , the superior mesenteric artery was taped at the trunk of the small bowel mesentery .\nabdominal aorta was clamped both at the head of celiac artery and at the level of renal artery to prevent blood flow .\nthe distal celiac artery of the aneurysm was cut and 8 mm size prosthetic graft was anamotosed .\nanother end of the prosthetic graft was anamostosed through the dorsum of duodenum to abdominal aorta below the level of renal artery ( fig.1d , e , f ) .\nceliac artery aneurysm is an uncommon type of splanchnic artery aneurysm that carries a high risk for mortality if it ruptures .\na total of 9.1% of celiac artery aneurysms are accompanied by abdominal aortic aneurysms ; solitary celiac artery aneurysms not accompanied by other aneurysms are extremely rare .\netiology of celiac artery aneurysm includes infectious diseases , atherosclerosis , trauma , or congenital conditions .\nother causes of celiac artery aneurysm include medial necrosis , inflammation , trauma , and median arcuate ligament syndrome . in our patient ,\nthe cause of the aneurysm was presumably derived from atherosclerosis due to the poor - controlled diabetes mellitus , hypertension , and aging .\nsince most patients are asymptomatic , celiac artery aneurysm is frequently incidentally discovered by imaging modalities for the investigation of other conditions or diseases .\nthe major presentation of celiac artery aneurysm is gastrointestinal symptoms , including abdominal pain , nausea , vomiting , appetite loss , or symptoms of mesenteric ischemia .\nthe risk of rupture of 1522 mm diameter celiac artery aneurysms is 5% ; in contrast , the risk of rupture in > 30 mm diameter aneurysms is 5070% . in general ,\ntreatment is considered for asymptomatic patients when the aneurysm is larger than 20 mm in diameter , .\nthe rudiment of operative treatment is the resection or closure of the aneurysm along with revascularization of peripheral branches that bifurcate from the celiac artery aneurysm .\nsurgical repair of the aneurysm with prosthetic grafts demonstrated more preferable long - term results than by using saphenous veins ; thereby , prosthetic grafts might become the mainstay of surgical aneurysm repair .\nsurgical treatment of a celiac artery aneurysm that involves the confluence of trifurcation is challenging , with a mortality risk of 5% , .\nwhen the aneurysm is removed without the vascular reconstruction , the blood flow from the super mesenteric artery to the hepatic artery should be carefully examined before surgery . in recent years , with advances in interventional radiology , catheter embolization is also attempted . when catheter embolization is adopted , the blood flow from the super mesenteric artery to the hepatic artery should be confirmed . clearly , if gross liver ischemia is found after aneurysm resection , revascularization of the hepatic artery is necessary , either by antegrade supraceliac aortohepatic bypass or retrograde inflow from the infrarenal segment of the aorta or the common iliac arteries . in our case ,\nangiography confirmed that the blood flow of the proper hepatic artery was dominantly supplied by the celiac artery and the gastroduodenal artery was patent and large .\nendovascular techniques , including stent implantation and embolization of aneurysms are feasible in the setting of advanced age and underlying diseases ; while surgical intervention is a safe and effective method in selected cases , . in our patient ,\nendovascular treatment was considered unsuitable because the patient just recovered from bacteremia and the possibility of an infective aneurysm could not be excluded .\nin addition , surgical intervention was not likely to be challenging considering the anatomical location of the aneurysm and the patient s favorable general condition . clearly , the celiac artery aneurysm in our patient was concluded not derived from infections based on the clinical course and operative findings .\na question may be raised about why this patient should have undergone ct although she did not present any abdominal complaints .\npatients with urosepsis should be scrutinized with imaging modalities in search of urological abnormalities or malformations irrespective of their symptoms .\nalthough rare , clinicians should be aware of celiac artery aneurysms and make efforts to discover them at an early stage , even during the investigation of other diseases or symptoms .\nfurthermore , early treatment of unruptured celiac artery aneurysm may sometimes be required to protect rupture or mesenteric ischemia from distal embolization .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .\nhiromichi naito , atsuyoshi iida , tetsuya yumoto and kohei tsukahara contributed to the study design , data collections , data analysis , writing and review .\nconsents , permissions , and releases were obtained where authors wished to include case details or images of patients and any other individuals in an elsevier publication .", "answer": "highlightsalthough rare , celiac artery aneurysm may carry a definite risk for rupture and other complications.because of its rarity , no strong consensus concerning indications for intervention of asymptomatic celiac artery aneurysm exists in the literature.clinicians awareness regarding this rare entity and efforts to discover before rupturing are imperative .", "id": 678} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nparrots are among the most endangered group of birds worldwide , and 15 of the 84 brazilian species are classified as being vulnerable or critically endangered .\nstudies on parrot populations are important to establish a database that can be assessed in the event of outbreaks , which could also be useful for subsequent epidemiological studies and conservation efforts\n. however , health surveys of free - ranging wild animals are mostly focused on retrospective studies on mortality [ 3 , 4 ] .\nresearch on diseases affecting free - ranging parrots is still scarce and studies performed often fail to maximize the scientific information that could be gathered [ 2 , 58 ] .\nsuch data could be of extreme importance in guiding conservation measures ex situ and in situ .\nthe hyacinth macaw and lear 's macaw are well - known flagship species that have suffered heavily owing to the destruction of habitat and illegal trade . a number of studies aimed at promoting their recovery have been performed and actions taken ; however , they are still classified as endangered species and face severe threats to their long - term survival . on the other hand ,\nthe blue - fronted amazon parrot is rated as a species of least concern regarding its conservation status .\nit is , however , the most illegally traded parrot species in brazil , and therefore , it is possible that decades of successive capturing of nestlings and concomitant ageing of the adult population could cause local extinctions in several areas where it is still common today .\nstudies have established that the intestinal flora of most species of healthy captive psittacines is composed essentially of gram - positive bacteria [ 11 , 12 ] .\nparrots in captivity are frequently affected by infections caused by gram - negative bacteria , and these microorganisms are considered either pathogenic or opportunistic .\none such bacterium , escherichia coli ( e. coli ) , is frequently involved in respiratory , digestive , and septicemic disorders in captive parrots .\nit is possible to classify e. coli into pathotypes by using genes responsible for the expression of virulence factors .\ncommonly described pathotypes include epec ( enteropathogenic e. coli ) , apec ( avian pathogenic e. coli ) , and upec ( uropathogenic e. coli ) [ 14 , 15 ] .\nepec is an important category of diarrheagenic e. coli and a major cause of infant diarrhea in developing countries , while apec is recognized for significant economic losses to the poultry industry , resulting in respiratory diseases and septicemia [ 14 , 15 ] .\nupec is a serious cause of urinary diseases in humans , causing cystitis that may progress to pyelonephritis .\nalthough , certain e. coli classification studies performed on wild birds [ 1722 ] and those involving captive psittacines have found a certain degree of correlation between disease and specific pathotypes [ 2325 ] , current serological methods to determine the pathogenicity of e. coli strains do not accurately predict which strains will be pathogenic in which birds .\nthe purpose of this study was to test cloacal samples from asymptomatic free - living nestlings ( blue - fronted amazon parrots as well as hyacinth and lear 's macaws ) to determine if they could be carriers of recognized e. coli pathotypes .\nin addition , we discuss the role that these strains could play in both free - living and captive parrots .\nthe samples of this study were collected during field surveys of the nestlings of hyacinth macaws and blue - fronted amazon parrots in the pantanal ( wetlands ) region of the refgio ecolgico caiman and neighboring farms ( 1958s , 5624w ) in mato grosso do sul state , and of lear 's macaws at the estao ecolgica de canudos ( 095348s , 390135w ) in the caatinga ( semi - arid ) of the bahia state .\ncloacal swabs ( cultureswab sterile , difco becton dickenson and company , sparks , maryland , usa ) were moistened with care using a sterile saline solution so as not to contaminate the swab during insertion in the cloaca .\nall chicks had no evident signs of disease ( soiled vent , emaciation , prostration , or delays in development according to their estimated age ) . in total ,\n44 samples were obtained , of which 10 were from hyacinths , 13 from lear 's , and 21 from blue - fronted amazon parrots .\nthe swabs were refrigerated up to processing at which point they were aerobically incubated in bhi broth ( brain heart infusion , difco ) for 24 hours at 37c .\nthey were then streaked onto macconkey ( difco ) agar plates and incubated for another 24 hours at 37c .\nbacteria were identified using a specific enterobacteria identification kit ( newprov , pinhais , paran , brazil ) and stored at 20c .\nisolates were tested using polymerase chain reaction ( pcr ) ( table 2 . ) , for the presence of e. coli attaching and effacing ( eae ) gene and bundle - forming pili structural ( bfpa ) gene of epec . for apec ,\nthe aerobactin ( iucd ) , cytotoxic necrotizing factor ( cnf1 ) , s fimbrial adhesin ( sfa ) , and p fimbrial adhesin ( papef ) genes were amplified .\nupec utilized alpha hemolysin ( hlya ) in addition to the genes used for apec .\nadditional apec genes for serum resistance ( iss ) and temperature - sensitive hemagglutinin ( tsh ) were also tested .\n\n e. coli was obtained from all 44 samples . details on the positive samples are given in table 1 .\none sample was positive solely for eae and not for bfp and was characterized as atypical epec .\na large number of samples were positive for virulence factors commonly found in apec ( 14 samples ) , with most originating from blue - fronted amazon chicks .\nthis gene was also found associated with other virulence factors in 4 samples , all from blue - fronted amazon parrots .\nthere was also an association between other virulence factors among some isolates ( table 1 ) .\nepec have the ability to cause lesions on the intestinal mucosa , leading to severe diarrhea .\nthis process is initiated by adherence to the epithelial cell membrane and is mediated by the adhesin intimin ( encoded by the eae gene ) .\ntypical epec strains possess both intimin and bundle - forming pili ( encoded by the bfp gene ) , which are responsible for the initial contact between the bacteria and the host cell ; atypical isolates , on the other hand , lack the bfp gene .\nhumans are considered the primary reservoir for the typical pathotype although it has also been found in dogs and cats [ 29 , 30 ] .\nthere are few reports of the presence of atypical epec in birds , especially the isolates obtained from poultry [ 3032 ] .\nthere are also reports of atypical epec causing fatal outbreaks in backyard passerine species , and carriers have been found among feral pigeons and rehabilitated seagulls [ 20 , 22 ] .\na study using 103 samples from captive psittacines detected 4 samples characterized as typical epec and 3 others as atypical isolates , all of which originated from clinical cases of diarrhea , enteritis , or septicemia .\nanother survey conducted in brazil regarding necropsy cases of symptomatic parrots also showed the presence of the eae gene in 2 atypical samples of e. coli isolated from the livers of 2 individual pet amazon parrots .\nthe fact that we found an atypical isolate in an asymptomatic bird , especially a free - ranging individual , suggests that this pathotype is not pathogenic in all parrots depending on the situation to which the birds are subjected .\napec and upec share several genes that encode virulence factors such as p fimbrial adhesin ( pap gene ) and s fimbrial adhesin ( sfa gene ) .\napec has been extensively studied in poultry where it has been observed that the p fimbrial adhesion enables binding of bacteria to internal organs and protects against heterophilic inflammation , while the s fimbrial adhesin is associated with omphalitis , salpingitis , chronic respiratory diseases , and sepsis .\nalthough several virulence factors have been associated with clinical cases of apec in poultry , no specific factor has been confirmed to be responsible for contributing to the pathogenicity observed , which makes it difficult to interpret results among lesser - studied groups such as wild birds .\nsiderophores , such as aerobactin ( iuc gene ) , enable e. coli to obtain iron stores from the host , and strains with this gene are quite frequently associated with clinical cases of poultry .\ntoxins , such as alpha hemolysin ( hlya gene characteristic of upec ) and cytotoxic necrotizing factor 1 ( cnf1 gene ) , provide the ability to cause tissue damage , contributing to dissemination and release of host nutrients while impairing the immune defenses . in this investigation , 2 samples were positive for the sfa and 1 was positive for the cnf1 gene .\nthese genes have been reported in pathogenic strains of e. coli isolated from septicemic poultry , as well as from human and domestic animals with extraintestinal pathogenic e. coli infections [ 16 , 34 ] .\na survey dealing with healthy feral pigeons detected a number of positive cloacal - swab specimens for the cytotoxic necrotizing factor 1 , showing the potential for disease spread by carriers of this species .\nother genes such as the tsh ( temperature - sensitive hemagglutinin ) and the iss ( increased serum survival ) are reported to be present in apec strains .\nthe increased serum survival causes sepsis by conferring resistance to the bacteria against the host immune bactericidal defenses .\nthe exact function of tsh is largely unknown , but it has been shown to be involved in mechanisms of adherence to the respiratory tract of poultry . in this study ,\nhowever , it has been shown in poultry that the presence of the iss gene alone may not be sufficient to identify apec isolates because this gene can also be found in the intestinal microbiota of healthy individuals , and an association with the iuc gene was reported to be necessary for achieving higher levels of virulence .\ninterestingly , a sample from an asymptomatic blue - fronted amazon chick in this study showed an association between the iss and iuc genes .\nthis research also found 1 positive sample for the iss / tsh association . in domestic turkeys ,\na relationship between clinical cases of colibacillosis and the presence of iss and tsh has been described .\nthe occurrence of gene associations such as iss / pap , iss / iuc / tsh , and pap / iuc / tsh has previously been reported in e. coli isolated from fecal , liver , and blood samples collected during necropsies performed in symptomatic psittacines in brazil .\nthese results in captive birds demonstrate that there is a connection between the presence of these genes and some clinical cases of colibacillosis as a contributing cause of death whether as primary or opportunistic pathogens . even though the sample numbers were too small to reach definite conclusions , we observed differences in the presence of virulence factors among the different species .\napec / upec genes were found mostly in species that usually nest on trees and live in a tropical climate ( at least in this studied area , for the species a. hyacinthinus and a. aestiva ) .\nepec was found in species that nest on limestone cliffs and inhabit semi - arid regions ( a. leari ) .\ndifferences among feeding habits , direct or indirect contact with other wild animals , and human activities ( interference due to human settlements and domestic animals ) could possibly have influenced these results , and thus , these results should be further investigated . \nalthough previous studies showed that some virulence factors are indeed involved in clinical cases of colibacillosis in psittacines [ 2325 ] , this investigation found a number of carriers for virulence factors .\nthese unusual findings focus the attention on the fact that , at least at the time of sampling , there was a stable host / parasite relationship . unlike wild birds , parrots maintained in captivity are frequently exposed to a number of factors that cause immunosuppression and increase their susceptibility to disease . these include deficient diets , inadequate hygiene , and lack of mental and physical stimuli ; all of these are factors that may determine the course of the disease when the animal is exposed to a microorganism .\nthe concept of disease is considered the result of an interactive relationship among the causative agent , the animal , and environmental factors , and a multitude of factors act together in order to initiate the disease process .\nif a factor is not present , it is probable that the organism will be capable of fighting the pathogen without showing overt clinical signs .\nthe nestlings in our study successfully fledged , indicating that although the potential for disease was present , birds living in their natural environment , without the factors induced by captivity , are more likely to remain disease free .\nthe results presented here are also important for the future conservation of the 2 endangered species ( a. hyacinthinus and a. leari ) as well as the heavily trafficked a. aestiva because they could better guide ex situ husbandry practices involved in captive breeding and rehabilitation / relocation programs , besides assisting monitoring of the overall health of the wild population . in conclusion , to our knowledge , this is the first study that tested e. coli virulence factors in wild psittacines .\nit is also the first to describe e. coli carriers in free - ranging parrots , and the results indicate that although the potential to develop disease was present , several factors that are most likely to be found in captivity needed to be involved in triggering disease development .\nother studies involving different species as well as a higher number of samples are important to further define the role and risks involved with specific e. coli pathotypes in the case of both wild and captive psittacines .", "answer": "parrots in captivity are frequently affected by escherichia coli ( e. coli ) infections . \n the objective of this study was to collect information on the carrier state for e. coli pathotypes in asymptomatic free - ranging parrots . \n cloacal swabs were collected from nestlings of hyacinth , lear 's macaws and blue - fronted amazon parrots and tested by polymerase chain reaction ( pcr ) for virulence factors commonly found in enteropathogenic , avian pathogenic , and uropathogenic e. coli strains . in total , 44 samples were cultured and e. coli isolates were yielded , from which dna was extracted and processed by pcr . \n genes commonly found in apec isolates from blue - fronted amazon parrots and hyacinth macaws were expressed in 14 of these 44 samples . \n one atypical epec isolate was obtained from a sample from lear 's macaw . \n the most commonly found gene was the increased serum survival ( iss ) gene . \n this is the first report , that describes such pathotypes in asymptomatic free - living parrots . \n the findings of this study suggest the presence of a stable host / parasite relationship at the time of the sampling brings a new understanding to the role that e. coli plays in captive and wild parrots . \n such information can be used to improve husbandry protocols as well as help conservation efforts of free - living populations .", "id": 679} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndouble male syndrome is a rare sex chromosome aneuploidy condition characterized by presence of two extra x and y chromosomes with an incidence of 1:18,000 - 1:40,000 male births .\nthis syndrome is clinically manifested later in life with developmental delays , learning disabilities , behavioral problems , and delayed or incomplete puberty .\nmany cases go undiagnosed as most of the above mentioned abnormalities do not develop until early puberty .\nthe term taurodontism was coined by sir arthur kein to describe the bull - like appearance of the teeth .\ntaurodontism can be defined as a morphological variation of a tooth in which the pulp chamber is vertically elongated and the roots are reduced in size .\nthe etiology of taurodontism is attributed to the failure of hertwig epithelial root sheath diaphragm to invaginate at the proper horizontal level .\nbased on the severity , taurodontic teeth can be classified ashypo- , meso- , and hypertaurodont forms .\nhypotaurodont expresses the least pronounced changes , while mesotaurodont expresses moderate variation , and hypertaurodont is characterized by the most severe variation in which the roots bifurcate or trifurcate close to the apices .\nthis is the first reported incidence of the endodontic management of a hypertaurodontic mandibular molar tooth in a patient diagnosed with 48 , xxyy syndrome .\na 19-year - old male reported to the postgraduate department of endodontics of our dental school , for management of multiple carious teeth . during history taking , it was elicited that the patient was a school dropout due to difficulty in coping with the educational curriculum .\nit was also evident , that the patient had below average communication skills with low self - esteem .\n( b and c ) postsurgical photograph after bilateral sagittal split osteotomy and genioplasty intraoral examination revealed dental caries in relation to teeth 15 , 37 , and 47 and multiple missing teeth ( 14 , 13 , 22 , 23 , and 36 ) .\nan orthopantomograph revealed multiple taurodontic teeth in relation to 37 , 46 , 47 , 17 , 26 , and 27 [ figure 2a ] .\nthe taurodontic teeth exhibited large pulp chamber extending beyond the cervical area and reaching the furcation suggestive of hypertaurodontism .\nthe tooth was nonsensitive to percussion , and radiographic interpretation was suggestive of asymptomatic apical periodontitis .\n( c ) a 2-year follow - up post endodontic restoration in 37 the complete endodontic management of the case was performed by one of the author , while the other author took care of post - endodontic restoration and clinical follow - up with department of oral surgery .\nthe patient was anesthetized with 1.7 ml of 4% articaine with 1:100,000 epinephrine ( septocaine , septodont , new castle , de , usa ) and access opening was performed under rubber dam isolation .\nendodontic treatment in taurodontic teeth has been described as difficult as the complex morphology could hamper the location of the root canal orifices .\nthe access opening and canal tracing was performed with the help of adental operating microscope ( g6 , global microscope , usa ) .\ncareful inspection and exploration revealed a large coronal pulp chamber extending 8 - 10 mm below the cervical margin ( cementoenamel junction ( cej ) ) .\nthe presence of two canals ( mesial and distal ) bifurcating 3 - 4 mm short of the radiographic apex was identified .\nan electronic apex locator ( root zx , morita , tokyo japan ) was used to determine the working length .\nthe shaping and cleaning of all canals was done using nickel - titanium rotary instruments , k3 ( sybron endo , orange , ca , usa ) .\nirrigation was done with 5.2% sodium hypochlorite solution ( naocl ) during shaping and cleaning of the root canal system .\npassive ultrasonic irrigation ( pui ) activation was employed using # 20/0.00 taper ss noncutting ultrasonic tip ( irrisafe , satelec , acteon , merignae , france ) followed by 1 min flush of 17% ethylenediaminetetraacetic acid ( edta ; smearclear , sybronendo , ca , usa ) .\nthe canals were dried using sterile paper points and dressed with intracanal calcium hydroxide medicament and the tooth was sealed temporarily with an intermediate restorative material ( cavitg , 3m - espe , seefeld , germany ) . the patient was asked to return after 2 weeks . at the second appointment\n, copious irrigation was done in order to remove the calcium hydroxide and the canals were made dry with sterile paper points . following radiographic control of the fit of gutta - percha mastercone ( guttapercha , sybronendo ,\nca , usa ) , the apical part of the main root canals was obturated with vertically compacted warm gutta - percha using the touch&heat 5004 device ( sybron endo , ca , usa ) .\nthe coronal portion of the main canal was backfilled with thermoplasticized gutta - percha using the obtura iigun ( obtura - spartan corp , fenton , mo , usa ) .\nthe access cavity was sealed with dualcuredcomposite resin ( paracore , coltene / whaledent , nj , usa ) .\nthe patient was then referred to the department of oral surgery for surgical correction of prognathic mandible .\nthe first stage involved a bilateral sagittal split osteotomy followed after 3 months by a second stage surgical advancement genioplasty procedure .\nfollow - up was at 6-months and 2-year intervals [ ure 1b and c ] .\na normal individual has 22 pairs of autosomes ( numbered chromosomes ) and one pair of autosomes and a single x and y chromosome , making a karyotype or chromosomal makeup of 46 , xy .\nsimilarly , a normal female has 22 pairs of autosomes and two x chromosomes , making a karyotype 46 , xx .\n48 , xxyy syndrome is characterized by an extra x chromosome and an extra y chromosome .\nthis , in addition to the 22 pairs of autosomes , males with 48 , xxyy syndrome has four sex chromosomes , making a karyotype 48 , xxyy .\nsuccessive meiotic nondisjuctional events during spermatogenesis , resulting in a xyy sperm have been attributed as the most probable etiological mechanism of 48 , xxyy syndrome .\nthe presence of extra sex chromosomes may lead to altered deoxyribonucleic acid ( dna ) methylation at various loci in genome leading to altered gene expression and subsequent phenotype variation . according to gardner and girgis ,\na patient with multiple taurodontic teeth without known association of any systemic syndrome should be consulted for chromosomal analysis , as there is a higher association of taurodontic teeth with x - chromosome aneuploidy syndromes .\nhence , we referred our patient to the department of human genetics for chromosomal analysis .\nchromosome analysis with gtg banding with a resolution of 450 - 550 bp , showed a numerical abnormality in all cells analyzed , with the presence of an extra x and an extra y chromosome resulting in 48 chromosomes and a diagnosis of 48 , xxyy syndrome was made [ figure 3 ] .\nchromosome analysis with gtg banding showing numerical abnormality in all cells with presence of extra x and y chromosome the prevalence of taurodontism ranges from 2.5 to 11.3% of the human population .\ntaurodontism can occur either as an isolated manifestation or in association with various systemic syndromes .\na literature search for relevant articles regarding endodontic management of taurodontic tooth associated with systemic syndromes was performed using ovid medline , cochrane database of systemic reviews , embase , and pubmed .\ntable 1 summarizes the chronological order of case reports of taurodontism associated with systemic syndromes .\nchronological reports of systemic syndromes associated with taurodontism this case showing 48 , xxyy karyotype is recognized as a distinct clinical and genetic entity .\nthis syndrome was previously considered to be a variant of klinefelter syndrome ( 47 , xxy ) ; however , it is now considered to be a distinct phenotype with more significant cognitive and psychological impairments .\nthe characteristic differences between these two syndromes have been well documented by tartaglia et al .\ncomparison of 47 , xxy klienfelter syndrome and 48 , xxyy syndrome ( adapted from tartaglia et al .\n, 48 , xxyy , 48 , xxxy , and 49 , xxxxy syndromes : not just variants of klinefelter syndrome , acta paediatr : 2011 ; 100(6):851 - 860 )\nknowledge regarding 48 , xxyy syndrome and its dentofacial manifestations is important for early diagnosis and long - term predictable medical and dental health management .\nan early recognition of such a disorder is crucial in improving the psychological as well a dental quality of life in affected patients .", "answer": "taurodontism is a developmental anomaly of a tooth characterized by large pulp chamber and short roots . \n patients with multiple taurodontic teeth are associated with the probability of a systemic syndrome or chromosomal anomaly . \n this is the first reported incidence of the endodontic management of a hyper taurodontic mandibular second molar in a patient diagnosed with 48 , xxyy syndrome .", "id": 680} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrheumatoid arthritis ( ra ) is a chronic , systemic inflammatory disorder that primarily targets the synovium and articular cartilage , leading to synovitis and progressive joint damage .\nhowever the pathophysiology of ra is poorly understood , the pro - inflammatory adipocytokines such as leptin , resistin and visfatin have been suggested to have an important role in the pathogenesis of the disease ( 1 ) . \nleptin , which is mainly produced by white adipose tissue ( wat ) cells , is a hormone encoded by the obese gene ( ob ) , the murine homologue of the human lep ( 2 ) .\nin addition to its well - known ability to regulate body weight by inhibiting food intake and increasing energy consumption , it also has inflammatory and immunomodulatory effects ( 3 ) .\nserum leptin levels were increased in ra patients compared to healthy controls ( 4 - 7 ) ; it was significantly higher in women than in men ( 8) .\nvisfatin , a growth factor for b lymphocyte precursors , is another pro - inflammatory adipocytokine , seen in liver , skeletal muscles and bone marrow and produced by visceral wat , which mimics the effects of insulin ( 9 , 10 ) .\nserum visfatin levels were increased in patients with ra ( 4 , 7 , 11 - 13 ) .\nrecently , reports have suggested the significant role of adipocytokines such as visfatin in mediating joint damage ( 4 , 14 , 15 ) .\nnevertheless , it is still a matter of debate whether infliximab significantly changes the visfatin levels ( 16 ) .\nthe purpose of this study was to examine the association between serum levels of adipocytokines ( leptin and visfatin ) and radiographic joint damage in patients with ra .\nthis study was conducted on 29 patients with erosive rheumatoid arthritis ( ra ) and 25 patients with non - erosive ra .\nall patients fulfilled the american college of rheumatology classification criteria for ra ( 17 ) .\neligible patients were those who met all of the following criteria : having ra for at least 1 year , but no more than 5 years ; aged between 20 and 50 at the disease onset ; and bmi 30 .\npatients were excluded if they had any of the following concomitant diseases : erosive joint diseases such as gout , seronegative spondyloarthropathies ; osteoarthritis ; blood pressure 140/90 mmhg ; cardiovascular diseases such as congestive heart failure or coronary artery diseases . \neach subject signed a written informed consent after explaining the objective of the study and verification of the inclusion and exclusion criteria .\nx - rays of the hands and feet were obtained from each of the subjects and 20 joints ( the wrists , 1 to 5 metacarpophalangeal joints , and 2 to 5 metatarsophalangeal joints ) were evaluated by a particular radiologist who was blinded to the study .\nthe amount of damage was quantified by using the larsen score , with ranging from 0 to 100 for all 20 joints ( 18 ) . \nafter overnight fasting , blood samples were drawn from all patients and stored at -20c until the time of analysis by leptin kit , ( visfatin kit : rav bio human visfatin e1 america ; me diagnose company , code : ref - e07 germany ) through elisa .\ndescriptive statistics were calculated as mean standard deviation ( sd ) or median [ interquartile range ( iqr ) ] according to distributions of continuous variables .\nstatistical analysis was performed with spss for windows software version 11.5 ( spss inc . ,\nthe mann - whitney test was used to determine the mean differences . for evaluating relationships among normally distributed variables ,\nthe pearson correlation coefficient was calculated , whereas the spearman 's rho was calculated in case of nonparametric data . \nstatistical analysis was performed with spss for windows software version 11.5 ( spss inc . ,\nchicago , il , usa ) . mean values and standard deviations were used for continuous variables . for comparing means ,\nthe mann - whitney test was used to determine the mean differences . for evaluating relationships among normally distributed variables ,\nthe pearson correlation coefficient was calculated , whereas the spearman 's rho was calculated in case of nonparametric data . \nin our study , age , sex and bmi did not show any statistically significant differences between the two groups of patients ( erosive and non - erosive ra ) ( p - values > 0.05 ) .\nthe median disease durations were 5 years ( iqr ( 3 - 5 ) ) and 2 years ( iqr ( 1 - 4.5 ) ) in patients with erosive and non - erosive ra , respectively ; which showed statistically significant differences between the two groups of patients ( p=0.003 ) .\nleptin concentrations did not show any statistically significant differences between the two groups of patients ( p=0.903 ) .\nvisfatin concentrations were significantly higher in patients with erosive ra ( 34.6 [ 29.1 - 100 ] ng / ml ) compared with non - erosive ra ( 28.4 [ 22.1 - 34.5 ] ng / ml ) ( p=0.013 ) ( table 1 ) . leptin and visfatin correlations with bmi , disease duration and larsen score are shown in table 2 .\nbmi correlated positively with leptin ( r=0.494 , p<0.001 ) , figure 1 while disease duration correlated positively with visfatin ( r=0.488 , p<0.001 ) figure 2 .\nno correlations were seen between larsen score and leptin and visfatin ( r= -0.318 , p=0.093 and r=0.254 , p=0.184 respectively ) . by using the linear regression coefficient model ,\nleptin showed correlation with bmi ( t=4.096 , p<0.001 ) and visfatin showed positive correlations with c - reactive protein ( crp ) and disease duration ( t=2.165 , p=0.035 and t=2.719 , p=0.009 respectively ) .\nnevertheless , using univariate variance analysis , there was no correlation between leptin and bmi in the two groups of ra ( p=0.508 ) , and leptin serum levels in the two study groups were not significantly different , not considering the bmi ( p=0.522 ) . while there was a positive correlation between visfatin and crp ( p=0.008 ) , no correlation was seen between visfatin and disease duration in the two erosive and non - erosive ra groups ( p=0.247 ) .\nthere are a few studies about the effect of adipokines like leptin and visfatin on radiographic changes of involved joints in rheumatoid arthritis . in giles\net al study , in 2009 , there was no association between the level of leptin and radiographic joint damage ( 14 ) .\nhowever , in rho et al studies , there was a positive correlation between these adipokines with radiographic changes , and higher levels of leptin were associated with less radiographic damage ( 13 ) . in this case - control study , we evaluated the association between the serum levels of leptin and visfatin with radiographic damage in two groups of patients with rheumatoid arthritis : with and without radiographic damage , to better understand the physiology of radiologic joint damage in rheumatoid arthritis patients which is the most important cause of morbidity in rheumatoid arthritis .\nwe found that serum levels of visfatin in our rheumatoid arthritis patients with joint erosion were much higher than those in patients without joint erosion .\nthere was no correlation between serum levels of visfatin with either sedimentation rate or crp .\nthere was a statistically significant positive correlation between visfatin serum levels with disease duration ( p<0.001 , r=0.538 ) .\nc - reactive protein level and disease duration were correlated to serum visfatin by linear regression method . \nunivariate analysis showed that serum visfatin in our two study groups had a statistically significant positive correlation ( p=0.008 ) with radiographic damage disregarding crp as co - founder ( p=0.008 ) .\nhowever , dispensing with the disease duration , visfatin serum levels in the two groups had no statistical significance ( p=0.695 ) .\nthese findings represent that serum visfatin level , independently , with serum crp as an inflammatory marker , is associated with joint damage in radiographic studies , but this correlation ( visfatin level and radiographic damage ) depends on the disease duration .\nour study was similar to the rho et al study in 2009 , which revealed that visfatin serum levels were positively correlated with radiographic joint damage considering age , gender , disease duration , bmi , and inflammation , with statistical significance ( 13 ) . \nalthough visfatin is an adipokine , based on previous studies , there is no correlation between visfatin and obesity ( 17 ) .\nhowever , some studies have shown that there is an association between visfatin and inflammatory markers ( 18 , 19 ) . in the rho\net al study there was a positive relationship between visfatin serum levels and inflammatory mediators like crp , tnf and il6 with statistical significance , but no correlation between visfatin and bmi . in our study , we could not find a correlation between bmi and visfatin levels .\nthis finding is probably due to the difference between inflammatory markers and also qualitative use of data in our study .\nbrentano and colleagues reported that visfatin was accumulated in the invasive synovial tissue in rheumatoid arthritis patients and its levels were increased in synovial fibroblasts as well ( 20 ) .\nvisfatin is able to induce il6 , matrix metalloproteinase ( mmp1 and mmp3 ) in synovial fibroblasts in ra patients and induce tnf and il6 in monocytes too ( 20 ) . in our study\n, we found that visfatin level is associated with radiographic damage and has a catabolic effect on joints ; therefore it has an important role in pathophysiology in rheumatoid arthritis . \nbusso et al , revealed that in arthritic rats , visfatin inhibitors induce remission exactly like tnf inhibitors ( 21 ) .\ninterestingly , pharmacologic inhibition in visfatin , decreases intracellular nad levels ( intracellular nucleotide adenine deaminase ) in inflammatory cells and reduces production of il6 and tnf in the involved joints of ra patients ( 21 ) . with respect to above findings\n, we can come to the conclusion that visfatin is an independent mediator in the pathogenesis of rheumatoid arthritis and is related to radiographic joint damage .\nvisfatin level was not related to esr , crp , larsen score or disease duration , but had a meaningful , positive statistical relation with bmi ( p=0.004 , r=0.385 ) .\nour study showed that leptin levels in ra patients with or without joint erosion were not any different .\nrho et al ( 13 ) showed that serum leptin level associated with less joint space narrowing after suppression of inflammatory process .\nalso there is a positive relation among leptin , das28 , crp , il6 , and bmi which is statistically significant in ra patients . in our study\n, we found a correlation between leptin and bmi and no association between leptin with disease activity , crp and il6 .\nthis discrepancy might be due to the design difference between our study and that of rho et al .\nwe did not evaluate disease activity score in our patients ; all patients had had rheumatoid arthritis for less than 5 years . according to the studies of westhoff et al ( 22 ) , kaufmann et al ( 23 ) and van der helmm et al ( 24 ) obesity has a protective effect in joint damage in ra patients ( 22 - 24 ) .\ntherefore , the important roles of adipocytokines like leptin and adiponectin in obesity should be considered in ra patients .\nwe found that visfatin level as an inflammatory marker , independently of crp level , is associated with joint radiographic damage and is related to disease duration .\nthe mechanism of visfatin as a proinflammatory and its catabolic role is not known and visfatin biology seems to be complex ; the key roles of visfatin as a treatment are still obscure . additionally , our study is one of the earliest in the field of association of adipocytokine levels and radiographic joint damage .\ntherefore , we suggest evaluating levels of adipocytokines before and after treatment in longitudinal studies to make clear the relationship between adipocytokines and joint damage in human models in the future . in future research , it would be reasonable to measure leptin and visfatin simultaneously , in addition to the other adipocytokines like adipocytokines of resistin .", "answer": "objective ( s):rheumatoid arthritis ( ra ) is a chronic systemic inflammatory disorder , primarily targeting the synovium and articular cartilage that leads to joint damage . \n recent reports have suggested the role of adipocytokines in mediating joint damage ; however it still is a matter of debate . \n the purpose of this study was to evaluate the association between serum values of adiopocytokines ( leptin , visfatin ) and radiographic joint damage in patients with ra.materials and methods : fifty - four patients diagnosed with ra , based on revised acr criteria 2010 , with 1 - 5 year disease duration since diagnosis , were enrolled . \n twenty - nine of patients had erosion in radiographic studies and 25patients had no erosion . \n radiographic joint damages were defined according to larsen score . additionally , serum levels of adipocytokines were measured and cross - sectional associations with radiographic damage were explored , adjusting for pertinent confounders.results:the serum level of visfatin were significantly higher in patients with radiographic joint damage compared with patients with no joint damage ( p=0.013 ) . \n this difference remained significant after adjustment for c - reactive protein levels ( p=0.008 ) , but not after adjustment for disease duration ( p=0.247 ) . the mean leptin serum levels were not different between these two groups ( p=0.903 ) . \n there was a positive correlation between leptin levels and bmi ( r=0.494 , p<0.001 ) . \n however , after adjustment for bmi , leptin levels had no difference between two groups ( p=0.508).conclusion : this study revealed that visfatin levels were significantly higher in patients with radiographic joint damage dependently to disease duration . \n therefore , it seems that adipocytokine may be a valuable factor in therapeutic targets in the future .", "id": 681} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncephalopelvic disproportion ( cpd ) in labour occurs when there is a mismatch between the size of the fetus and the dimensions of the maternal pelvis .\nthe factors which mainly influence the outcome of the delivery can be summarised as the three ps of the labour : passageway , passenger , and power of the uterus .\nthe passageway component of this trinity has been investigated by pelvimetry which measures the maternal bony pelvic dimensions , with very little emphasis on its shape or pelvic floor muscles . during the last decades , the use of pelvimetry has been discouraged , but at present , no replacing methods to evaluate the maternal pelvis have been introduced .\nthe benefits of vaginal deliveries are well known when no risk factors are present even after previous cesarean section ( cs ) [ 5 , 6 ] . on the other hand , unplanned interventions during labour such as acute or emergency cesarean sections as well as operative vaginal delivery increase both maternal and fetal morbidities as does a prolonged second stage of the delivery .\nthe safety and the accuracy of the measurements obtained in pelvimetry have improved in the era of the mri technology [ 9 , 10 ] .\nit is also in the interest of the mother and her physician to minimize the number of unplanned interventions during labour .\nthe purpose of this observational cohort study was to evaluate whether pelvic measurements , especially pelvic outlet , displayed any association with operative vaginal deliveries and the duration of the second stage of the delivery .\nthis retrospective study was approved by the ethical committee of north - carelian central hospital .\nit investigated caucasian women , that had been examined by x - ray or mri pelvimetry during 20002008 in north - carelian central hospital .\neligibility criteria included that pelvimetric and fetal measurements had been recorded . in the operative delivery group ,\nthere were no signs of fetal distress in cardiotocography , inertia was not diagnosed , and there was no malpresentation .\noriginally , 915 women were screened for possible inclusion , but 429 women were excluded because of breech presentation .\na total of 486 patients with the fetus in the cephalic presentation were screened in the study , but those 234 women that went through elective or acute cesarean section were excluded from the analysis .\nthe clinical indication for pelvimetry was breech presentation , or if the fetus was in cephalic presentation , the indication was suspected cephalopelvic disproportion in clinical examination .\nthe findings that referred to cpd in clinical examination were clinically small pelvis , unengaged presentation , or suspected macrosomia .\npelvimetric measurements were found in all patients , as required by the inclusion criteria . there were 252 participants with fetal cephalic presentation delivered vaginally , of whom 184 women delivered spontaneously and 68 women went through operative vaginal delivery with vacuum extraction . of this latter group of women , in 26 patients , the vacuum extraction was undertaken primarily because of fetal distress and inertia , and these patients were excluded from the final analysis , leaving 42 women in the operative vaginal delivery group .\nthus , the total number of participants evaluated in the final stage of this study was 226 .\nthe obstetric and radiologic data were collected from patients ' medical records by the author ( uk ) and transferred into a commercially available worksheet ( excel , microsoft 2003 , ireland ) .\nthe following pelvimetric parameters were recorded : in the pelvic inlet , anteroposterior ( conjugata vera ) and transverse diameters and in outlet , interspinous diameter and sagittal diameter from the surface of the pubic symphysis to the surface of the sacrum measured at the spinous level .\npelvic inlet and outlet circumferences were calculated from the pelvic anteroposterior and transverse diameters using the formula ( ap + dt 1.57 ) .\nuntil the year of 2003 , all pelvimetries were performed with an x - ray technique , and from the year 2004 onwards , they were performed with magnetic resonance imaging ( mri ) . during the transition period\n, both x - ray and mri pelvimetries were performed to verify the repeatability of the measurement results . already at the beginning of 1990 , in order to minimize the variability in pelvimetric measurements , they were centralized so that instead of being conducted by several radiologists , they were conducted by trained obstetricians . when the mri pelvimetry was taken into clinical practice , there was one radiologist with previous experience of mri pelvimetry , and during a two - year period ( 20042006 ) , three radiologists and further three obstetricians were also trained to measure the images . in this evaluation of the diagnostic accuracy of the pelvimetry in vaginal deliveries ,\npatients were divided into subgroups according to the size of the fetus and also by the parity to evaluate the variability reflecting differences in patient groups . for statistical analysis , we used spss 17.0 ( spss inc . , 2009 ,\nreceiver operating characteristic ( roc ) curves were established , and the area under curve ( auc ) values with significances were calculated .\npelvimetric measurements were found in all patients , as required by the inclusion criteria . in the spontaneous vaginal delivery group ,\nmost of the nulliparous patients were sent to maternity clinics consultation because of suspected disproportion . in the multiparous group ,\n24% had delivered by cs and 37% by operative vaginal delivery . in the operative vaginal delivery group ,\nof the nine multiparous patients , six had delivered by cs in their previous pregnancy and two had had previous vaginal operative delivery .\nthe demographic data of these 226 patients subdivided according to the route of delivery are shown in table 1 .\npatients were further subdivided into two subgroups according to the infant 's weight and the mode of delivery .\nthe maternal pelvic inlet and outlet sizes and duration of the first and second stages of the delivery by the mode of delivery in infant weight subgroups are shown in table 2 .\nthe mean maternal outlet ( sd ) was 3613 ( 20 ) mm in all , 351 ( 17 ) mm in infant weight < 3700 g , and 369.5 ( 17.7 ) mm in infant weight 3700 g groups .\nno clinically or statistically significant differences in the pelvic sizes were found between the modes of delivery within the subgroups . between the subgroups ,\nthe size of the maternal pelvic size was 4%-5% larger in the mothers with infant weight 3700 g. the duration of the second stage of the delivery was 54 minutes longer ( p < 0.01 ) in the operative vaginal delivery group amounting to a 45-minute longer duration ( p = 0.01 ) in infant weight < 3700 g and 62 minutes longer ( p < 0.01 ) in infant weight 3700 g group .\nthe one - minute apgar scores were above 8 in all groups with the exception of those with infant weight less than 3700 g in the operative vaginal group , where the mean of apgar score at one minute was 7.8 1.8 .\nthe receiver operating characteristic curve analysis for pelvic inlet and outlet as a diagnostic test for the mode of vaginal delivery is shown in figures 2(a ) and 2(b ) .\nthe area under the curve ( auc ) for the pelvic inlet was 0.566 with the p value of 0.18 and 95% confidence interval ( ci ) of 0.4650.667 . for pelvic outlet ,\nthe main finding of this study was that the maternal bony pelvic dimensions displayed virtually no correlation to the need for operative vaginal deliveries .\nthe indications for intervention in vaginal deliveries were chosen on clinical grounds as evidenced by the fact that there was an association between the duration of the second stage of the delivery and the size of the pelvic outlet . if the delivery had reached the second stage , it was probable that the uterine power played a more significant role in the overall outcome than either the passageway or the passenger . on the other hand , pelvic floor muscles , the three - dimensional shape of the bony pelvis , or other soft tissues\nthe pelvimetry was performed in most of the patients because of suspected disproportion , or an intervention had been required in a previous labour .\nof those patients that had previous cs and were now exposed to the trial of labour , over 80% delivered spontaneously , and less than 20% required an operative vaginal delivery .\nthis is in agreement with previous studies [ 6 , 13 ] . of those women\nthat had had a previous operative vaginal labour , only 5% underwent repeated vaginally assisted delivery .\nthis may have been due to the fact that the patients were chosen for the trial of labour correctly irrespective of the previous operative delivery .\nthere were no statistically significant differences between the size of the maternal inlet or outlet in the spontaneous and the operative vaginal delivery groups .\nwhen patients were divided into subgroups according to the infant weight , the maternal inlet was 4.7% and the outlet was 5.1% larger in the infant weight 3700 g subgroup among those who delivered spontaneously compared to those vaginally assisted .\nthe duration of the first stage of the delivery was longer in the smaller infant group , whereas the second stage was shorter than in the larger infant group .\nin the two delivery subgroups , the duration of the second stage of the delivery was significantly longer in operative vaginal delivery group than in spontaneous vaginal delivery group .\nthe apgar scores were acceptable in all delivery groups referring to the fact that both spontaneous and operative vaginal deliveries were uncomplicated and severe shoulder dystocia was not present .\nthe apgar 1-minute scores were lower in the operative vaginal delivery group than in spontaneous vaginal delivery group when infant weight was < 3700 g. these results refer to the fact that operative vaginal delivery increases the time of the second stage of the delivery and decreases the apgar 1-minute scores .\nthe roc curve analysis for maternal pelvic inlet and outlet revealed that both inlet and outlet had only a fair prognostic value in predicting the mode of the vaginal delivery .\nthe poor predictive value of pelvimetry to predict protracted labor is a well - known fact from previous studies , whereas the evidence on the need of vaginal operative deliveries is less extensively evaluated .\nthe data did not reveal in detail the fluency of the operative deliveries . as mentioned earlier ,\ntherefore , it was not possible to evaluate the influence of the pelvic dimensions on the severe dystocia .\nfor that kind of study , the cohort examined here study is too small due to the rare incidence of severe dystocia .\naccordingly , due to the retrospective nature of the study , no blinding was present , and the caregivers were aware of the pelvimetric measurements during the labour .\nfurthermore , the study women were at high risk of operative deliveries due to the inclusion criteria , but in clinical care , this would be the group eligible for pelvic assessment before delivery . in conclusion\n, our study revealed that maternal bony pelvic dimensions , either pelvic inlet or outlet , were not associated with the need for operative vaginal deliveries .\nit was more likely that other factors related to the maternal perineal soft tissue , maternal resources , and the passenger were the reasons leading to operative vaginal deliveries .\nsubsequently , we can not recommend that caregivers use pelvimetric measurements to predict the outcome of the second stage of the labour .\nobservational studies with larger cohorts would be needed , if one wished to investigate whether the maternal bony pelvic size has any effect on severe dystocia .\nin addition , the three - dimensional shape of the bony pelvis and the soft tissues are worth considering in future studies .", "answer": "objective . to evaluate whether pelvic measurements have any association with operative vaginal deliveries and the duration of the second stage of \n the delivery \n . study design . a retrospective study of pregnant women at an increased risk of fetal - pelvic disproportion during 20002008 in north - carelian central hospital . \n the mode of the vaginal delivery was chosen to represent the reference standard . \n the target condition was spontaneous vaginal delivery . \n patients were divided into subgroups according to the size of the fetus and also by the parity to evaluate the variability reflecting differences in patient groups . \n receiver operating characteristic ( roc ) curves were established . \n results . a total of 226 participants with fetal cephalic presentation delivered vaginally ; of these \n , 184 women delivered spontaneously , and 42 women required operative vaginal delivery with vacuum extraction . \n there were no clinically or statistically significant differences between the size of the maternal pelvic outlet and the different modes of delivery types within these subgroups . \n with respect to the pelvic inlet and outlet , the areas under the curve in roc were 0.566 with the \n p value of 0.18 and 95% confidence interval ( ci ) of 0.4650.667 and 0.573 ( 95% ci : 0.4840.622 ; p = 0.14 ) . \n conclusions . \n the maternal bony pelvic dimensions exhibited virtually no correlation with the need for operative vaginal deliveries .", "id": 682} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhand , foot , and mouth disease ( hfmd ) is a common , acute , and mostly self - limiting enteroviral infection that presents with fever and vesicular lesions on the hands , feet , mouth , and frequently buttocks as characteristic features1,2,3,4 ) .\nalthough patients with hfmd recover without any sequelae within about 1 week , severe complications occur in a few cases , some of which are life threatening .\nsevere complications accompanying hfmd include encephalitis , pulmonary edema / hemorrhage , cardiopulmonary collapse , and myocarditis1,2 ) .\nenterovirus 71 can often lead to a more severe clinical course accompanied by neurologic and cardiopulmonary complications and may rapidly lead to death1,2,3 ) .\nenterovirus 71-induced hfmd developed in korea in 2000 but it was not an epidemic and fatal until 20081,4,5 ) . in the spring of 2009 , a large nationwide outbreak of hfmd caused by enterovirus 71 occurred in korea , and a few cases with encephalitis were fatal1,4,6 ) . a multicenter study in korea performed by the enterovirus complication working group revealed that encephalitis with cardiopulmonary complications of hfmd occurred in 2.4% of patients , including 2 patients ( 1.2% ) who expired1 ) .\npulmonary hemorrhage in enterovirus 71-infected hfmd patients has been reported in taiwan , china , and malaysia2,7,8,9 ) .\nhowever , to our knowledge , no cases of hfmd with sudden - onset massive pulmonary hemorrhage have been reported in korea . here\n, we report a fatal case of enterovirus 71-induced hfmd that progressed rapidly with massive pulmonary hemorrhage and convulsion .\na 12-month - old , previously healthy boy with hfmd was referred to inje university ilsan paik hospital because of 3 episodes febrile convulsions .\nhe was born at full term weighing 3.87 kg through normal vaginal delivery by a vietnamese mother .\nhe was admitted to a primary hospital with high fever ( up to 39 ) , throat vesicles , and vesicular rashes on his hands and feet for 2 days . on the second hospital day , he had 3 generalized tonic - clonic and atonic convulsions with vertical eyeball deviation within 5 minutes of each other .\nhis chest radiography was normal . within 5 hours after admission , he vomited 3 times after meals . besides a body temperature of 38.3 , his other vital signs were stable and he remained conscious .\ndesaturation to 76% percutaneous blood oxygen saturation ( spo2 ) and tachycardia to 176 beats / min accompanied by perioral cyanosis occurred suddenly 6 hours after admission .\nhis respiration rate was 34 breaths / min , and auscultation disclosed rales on the whole lung field .\nan endotracheal tube was inserted immediately , and a large amount of blood from a pulmonary hemorrhage came out through it .\ncomparison of laboratory test results between his initial and pulmonary hemorrhagic status revealed that his hemoglobin decreased from 9.6 to 8.3 mg / dl and his white blood cell count increased from 13,090 to 17,450 cells/l .\nerythrocyte sedimentation rate was slightly increased from 15 to 32 mm / hr , but c - reactive protein level decreased from 1.06 to 0.2 mg / dl .\nprothrombin time ( pt ) and pt international normalized ratio were slightly prolonged ( 16.5 and 1.39 seconds , respectively ) .\nmeanwhile , d - dimer ( 2,375.91 ng / ml ) and fibrin degradation product ( 5 - 20 g / ml ) were elevated .\neight hours after admission , his blood pressure decreased to 82/41 mmhg and heart rate increased to 220 beats / min .\nhis body temperature ranged from 38.8 to 40.2. the patient was diagnosed as fatal hfmd with massive pulmonary hemorrhage .\nintravenous immunoglobulin ( ivig , 1 g / kg / dose ) , dexamethasone ( 0.3 mg / kg / day in divided doses every 6 hours ) , and cefotaxime ( 150 mg / kg / day in divided doses every 6 hours ) were administered immediately .\nin addition , leukocyte - depleted red blood cells and fresh frozen plasma were transfused , and intravenous vitamin k and endotracheal epinephrine were administered .\nlumbar puncture was scheduled but was ultimately not performed because of the patient 's unstable vital signs .\nthe patient expired 15 hours after admission , and it was within 3 days of fever onset and within 9 hours after intubation .\nwe reported it to the korea centers for disease control and prevention ( kcdc ) , sending his urine , serum , nasopharyngeal swab , and endotracheal aspirate .\nenterovirus genome detection was attempted by realtime reverse transcription - polymerase chain reaction ( rt - pcr ) using a taqman system ( applied biosystems , foster city , ca , usa ) . for genotyping ,\nseminested rt - pcr was used to amplify part of the viral protein 1 ( vp1 ) gene of enteroviruses according to the kcdc protocol , and sequencing analysis for the vp1 amplicon was performed by an automatic sequencer and the dnastar software package ( dnastar inc . , madison , wi , usa ) .\nthe kcdc isolated enterovirus 71 with subgenotype c4a from the patient 's serum and nasopharyngeal swab .\nbocavirus was also isolated from his nasopharyngeal swab by real - time rt - pcr at our hospital .\nto our knowledge , this is the first reported case of hfmd with sudden - onset massive pulmonary hemorrhage in korea .\npulmonary edema / hemorrhage is the mysterious hallmark symptom of enteroviral hfmd and can kill a child within 1 day2 ) .\nan epidemic study conducted in taiwan from 1998 to 2005 reported that pulmonary edema / hemorrhage occurred in 43% of patients with severe culture - proven enteroviral hfmd / herpangina2 ) .\nthis discrepancy maybe due to different enterovirus virulence or subgenotypes , or differences in susceptibility with respect to ethnicity .\npulmonary edema / hemorrhage is characterized by respiratory distress , tachypnea , tachycardia , hemoptysis , and rapidly progressing diffuse infiltration or congestion on a chest film2 ) .\na study on the outbreak in taiwan in 1998 reported that enterovirus 71-infected hfmd patients with pulmonary edema had suddenonset tachypnea , tachycardia , and cyanosis within 1 - 3 days after disease onset , and pulmonary edema led to a rapid death within 12 hours after intubation10 ) .\nthe present patient exhibited a change in consciousness , respiratory distress , tachypnea , tachycardia , hemoptysis , rapidly progressing infiltration on a chest film , hypoxemia , and hypotension .\nthis patient ultimately expired within 3 days of fever onset and within 9 hours after intubation . in this report , we had applied pulse oxymetry from the beginning , so we could find his desaturation immediately after pulmonary hemorrhage .\nwe suggest saturation monitoring for hfmd patients with central nervous system ( cns ) involvements for early detection .\nit may be caused by increased pulmonary vascular permeability as a result of either brainstem encephalitis or a systemic inflammatory response caused by excessive cytokine release2,6 ) .\ncns involvement of enterovirus 71-induced hfmd may also trigger a sympathetic storm , resulting in vasoconstriction with high systemic vascular resistance , passive pulmonary volume loading , and pulmonary edema / hemorrhage8 ) .\nthe present patient had several episodes of convulsions , lethargy , and loss of consciousness .\ntherefore , we suspected encephalitis , although we were unable to perform a cerebrospinal fluid study because of his unstable vital signs . his suspected encephalitis may be a possible cause of the pulmonary hemorrhage . however , pulmonary edema / hemorrhage without cns involvement occurred in 11% of patients with severe culture - proven enteroviral hfmd / herpangina in an epidemic study in taiwan from 1998 to 20052 ) .\nanother possible explanation for the pathogenesis is coinfection with a second virus2 ) , as bocavirus coinfection was detected in the patient .\nhowever , the presence of both viruses would not result in increased mortality due to hfmd , according to a previous study2 ) . a multicenter study performed by the enterovirus complication working group investigating enterovirus 71-induced hfmd in korea in 2009 reported that an hfmd rash pattern , fever longer than 4 days , peak body temperature > 39 , vomiting , headache , neurologic signs , leukocytosis , serum glucose > 100 mg / dl , and isolated enterovirus 71 may be indicative of poor prognosis during hfmd epidemic periods1,10 ) .\nin addition , young age at disease onset and a history of lethargy are associated with an increased risk of severe hfmd11 ) .\nthe present patient was young and presented with hfmd rashes and vesicles , fever up to 39 , vomiting , lethargy , and convulsions as neurologic signs as well as leukocytosis , high serum glucose level , and isolated enterovirus 71 as poor prognostic factors .\nhfmd patients are very frequently approximately 1 year of age , and deaths were reported to occur at around 1 year of age in other studies12,13,14,15 ) . in the 2009 outbreak ,\n2 patients around 1 year of age expired , and the present patient was a 12-month - old baby .\nthe gold standard for the diagnosis of enteroviral infection is viral culture and isolation in 2 or more specimens of cerebrospinal fluid , blood , nasopharyngeal swab or secretion , vesicular fluid , or stool to increased diagnostic sensitivity1,4,6,11 ) . in the present report ,\nenterovirus 71 was isolated from both the patient 's serum and nasopharyngeal swab . in the 2009 korean outbreak ,\nthe subgenotype of enterovirus 71 was c4a , which was prevalent in china in 2008 . in the present case , the subgenotype of enterovirus 71 was also c4a .\nthe administration of high - dose ivig is recommended for severe hfmd as optional treatment , because ivig therapy was effective in many reports4,5,6,7,11 ) .\nivig neutralizes the virus and has nonspecific antiinflammatory properties11 ) ; this would significantly reduce mortality by attenuating sympathetic activity and cytokine production5 ) .\nfurthermore , fluid restriction , inotropic agents , and early intubation with positive - pressure mechanical ventilation are recommended for severe hfmd with pulmonary edema or hemorrhage8 ) .\npulmonary hemorrhage in enterovirus 71-infected hfmd is very rare ; the present case is likely the first to have occurred in korea .\nthe present case of fatal hfmd was rapidly aggravated and the patient expired within 3 days from fever onset .\ntherefore , all physicians should pay special attention to infants and young children with hfmd , particularly in enterovirus 71 epidemic areas such as korea , to enable early detection and management of severe hfmd .\nabove all , keeping the infected child at home until full recovery and controlling the preschool with infected child are very important for reducing infection6 ) .\nin addition , the development of antiviral agents and vaccines is necessary especially for the control of severe hfmd with complication .", "answer": "hand , foot , and mouth disease ( hfmd ) is an acute , mostly self - limiting infection . \n patients usually recover without any sequelae \n . however , a few cases are life threatening , especially those caused by enterovirus 71 ( ev71 ) . \n a 12-month - old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth , hands , and feet . \n after 3 days , he experienced 3 seizure episodes and was referred to our hospital . on admission , he was conscious and his chest radiograph was normal . however , 6 hours later , he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death . \n he experienced several more intermittent seizures , and diffuse infiltration of both lung fields was observed on chest radiography . \n intravenous immunoglobulin , dexamethasone , cefotaxime , leukocyte - depleted red blood cells , fresh frozen plasma , inotropics , vitamin k , and endotracheal epinephrine were administered . \n the patient died 9 hours after intubation , within 3 days from fever onset . \n ev71 subgenotype c4a was isolated retrospectively from serum and nasopharyngeal swab by real - time reverse transcription - polymerase chain reaction . here , \n we report a fatal case of ev71-associated hfmd with sudden - onset massive pulmonary hemorrhage and suspected encephalitis .", "id": 683} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncutaneous leishmaniasis ( cl ) is an endemic parasitic disease in middle - east countries including iran .\nmost skin lesions evolve from papular , nodular , and plaques . however , there are rare clinical forms including , disseminated cl ( dcl ) , sporotrichoid , and lupoid which are related to host immunity .\ndelayed - type hypersensitivity is an important feature of the disease pathogenesis , and it can be measured by leishmanin skin test ( lst ) , also called montenegro test . in disseminated type , lst and other tests of specific cellular immunity\nare negative , and affected patients with lupoid leishmaniasis have a vigorous cellular immune response but low antibody titer . in sporotrichoid type of cl , there is lymphatic dissemination in the form of subcutaneous nodules ( scn ) .\nhowever , there is no report of evaluation of host cellular immunity in these cases .\nthe aim of this study was to determine and compare the patients reactivity to lst in three forms of cl , including common plaque type [ figure 1 ] , lupoid type [ figure 2 ] , and sporotrichoid type [ figure 3 ] .\nthis was a descriptive cross - sectional study performed in skin disease and leishmaniasis research centre , isfahan , iran .\nthe patients enrolled in this study had cl confirmed by positive direct smear of their lesions and had three clinical forms of common plaque type , lupoid type , and sporotrichoid type .\npatients more than 60 and less than 5 years old , those with any kind of state which affects the immune system such as underlying disease , pregnancy , hypersensitivity disorders , and steroids intake and clinical course shorter than 2 months were excluded from the study . after being informed about the study , the patients or the guardians signed a consent form , and then lst was performed for them .\neach test vial contains 1 ml phosphate buffered saline , 0.1% thiomersal , and 610 6 killed l.major promastigotes .\nlst was carried out by injecting 0.1 ml of a suspension of antigen intradermal with a 27-g needle in volar aspect of right forearm . in order to minimize the placebo effect\n, we also injected a control solution supplied from the same institute containing 1 ml pbs and 0.1% thiomersal in the contralateral side .\nthe reaction was read after 48 h and the induration was measured by ballpoint technique . in the case of no reactivity , the test would be observed at 72 h of the injection .\nresults were categorized as negative ( 0 - 5 mm induration ) , positive ( 6 - 14 mm ) , and strongly positive ( 15 mm ) . with a special notice to the fact that in the site of injection of control solution , there should be no reaction .\n( chicago , usa ) version 16 software using kruskal wallis and analysis of variance .\ntotally , 500 patients suspected to cl were referred to skin diseases and leishmaniasis research center from august 2010 to december 2011 , of which 200 parasitologically confirmed cases with three different types of cl were enrolled in the study and underwent lst .\nhundred and forty - three patients had common plaque type , 24 patients had lupoid type , and 33 were diagnosed with sporotrichoid type of cl .\nthe mean duration of the disease was 5.99 1.04 ( min : 2 months and max : 96 months ) . in the group with plaque type ,\n86% had a positive lst , 13.3% were negative , and 0.7% were strongly positive .\nin the lupoid group , these figures were 45.8% , 8.4% , 45.8% , respectively . in the sporotrichoid group ,\nlst was positive in 27.3% , negative in 72.7% , and none of the patients had a strongly positive reaction ( p < 0.05 ) .\nthe minimum mean induration was in sporotrichoid group which was 3.30 2.24 mm and the maximum mean induration with 11.2 6.10 mm belonged to the patients with lupoid type [ table 1 ; figures 4 and 5 ] .\nthe results of leishmanin skin test in three groups of cutaneous leishmaniasis with different clinical forms positive leishmanin skin test exaggerated positive leishmanin test in lupoid type\nthe lst or montenegro test is an important tool for the diagnosis and epidemiological surveys of cl . because of the high sensitivity of lst in cl\nthe test becomes positive a few weeks after infection and it is a decisive method for the diagnosis of older leishmanial lesions , when the number of parasites is low and therefore , difficult to detect .\nthe test is useful for follow - up in vaccination programs , and is also used as a parameter for evaluating the development of immune protection .\nthe lst consists of the intradermal injection of a suspension of antigen prepared from dead promastigotes , and relies on the cell - mediated immune response that usually occurs with cl .\nthe reaction read at 48 - 72 h. understanding the timing of lst is of significant importance to avoid false - negative results in those few cases that present with early disease ; therefore , we excluded the patients with a clinical course shorter than 2 months .\nwe also excluded patients with any kind of possible impairment in the immune system in order to avoid possible negative effects on test results . protective immunity against leishmaniasis\nis largely , if not wholly t - cell mediated and associated with production of interferon gamma . in this study ,\nthe test was supplied from pastor institution , tehran , iran , where the safety and efficacy of it have been previously documented .\nit is negative in patients with very recent cl infection and dcl . whereas in lupoid\nleishmaniasis which is a rare peculiar form of chronic cl , a vigorous cellular immunity response and low number of parasites in lesions have been shown .\nthis recurrent form of the disease refers to the development of the new lesions within the scar of the healed lesions mimicking lupus vulgaris .\nsporotrichoid type of cl is a clinical form of cl that represents lymphatic dissemination , a phenomenon not widely recognized in the form of scn and is seen in 10% of cl patients .\nthe scn were usually inconspicuous , painless , proximal to the primary skin lesions when multiplied they show sporotrichoid configuration .\nthe results of our study showed that most of the positive lst results belong to plaque and lupoid groups , the majority of strongly positives belong to lupoid , and the most of negative lst results were related to sporotrichoid type , the negativity of leishmanin test in some patients with plaque and lupoid types can be explained by the sensitivity of the test used which is 88% according to our results .\nin addition , the mean induration in sporotrichoid group was less than the other two groups . according to results obtained from this study\nit can be suggested that lupoid and sporotrichoid types of cl are parts of a continuous spectrum of the disease with an enhanced cellular immunity in lupoid form and a decreased state in sporotrichoid type .", "answer": "introduction : cutaneous leishmaniasis ( cl ) is a parasitic disease which has different clinical forms . \n the aim of this study is to compare the response to leishmanin skin test ( lst ) in three forms of cl including plaque type , lupoid type , and sporotrichoid type.materials and methods : this was a descriptive cross - sectional study . \n the patients enrolled in this study had three clinical forms of cl confirmed by positive smear of their lesions and then lst was performed for them . \n results were categorized as negative ( 0 - 5 mm induration ) , positive ( 6 - 14 mm ) , and strongly positive ( 15 mm ) . the data were documented in the patients files and analyzed with spss windows software version 16 ( inc.chicago , usa).results:200 patients were enrolled in the study . in the group with plaque type , 86% had a positive lst , 13.3% were negative , and 0.7% were strongly positive . in the lupoid group , these figures were 45.8% , 8.4% , 45.8% , respectively . in the sporotrichoid group , lst was positive in 27.3% , negative in 72.7% , and none of the patients had a strongly positive reaction ( p < 0.05 ) . \n discussion : the most of the positive lst were belong to plaque and lupoid groups , the most of strongly positive were belong to lupoid , and the most of negative lst were related with sporotrichoid type.conclusion:it can be suggested that lupoid and sporotrichoid types of cl are parts of a continuous spectrum of the disease with an enhanced cellular immunity in lupoid form and a decreased state in sporotrichoid type .", "id": 684} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na lot of research has been done in the past , and still research is going on to explore tools and techniques for regeneration of lost tissues as a result of the disease process .\nthe use of various grafts and recent tissue engineering techniques including stem cell research are testimony to the ever increasing need for most suitable treatment option to replace / repair lost tissues due to various pathologic processes .\nthe use of autogenous periosteum in general medical treatment has been extensive and has shown promising results [ 13 ] ; on the contrary in dentistry , the use of periosteum as a regenerative tool has been limited and highly underrated ; therefore , the purpose of this paper is to highlight the current status of use of periosteum in dentistry as well as suggesting its future use in various treatment options related specifically to dental field .\nthe periosteum is a highly vascular connective tissue sheath covering the external surface of all the bones except for sites of articulation and muscle attachment ( figure 1 ) .\nthe periosteum comprises of at least two layers , an inner cellular or cambium layer , and an outer fibrous layer .\nthe inner layer contains numerous osteoblasts and osteoprogenitor cells , and the outer layer is composed of dense collagen fiber , fibroblasts , and their progenitor cells ; osteogenic progenitor cells from the periosteal cambium layer may work with osteoblasts in initiating and driving the cell differentiation process of bone repair characterized by the development of the initial fracture callus and subsequent remodeling .\nperiosteum can be described as an osteoprogenitor cell containing bone envelope , capable of being activated to proliferate by trauma , tumors , and lymphocyte mitogens .\nresearch on the structure of periosteum has shown that it is made up of three discrete zones .\nzone 1 has an average thickness of 1020 um consisting predominantly of osteoblasts representing 90% of cell population , while collagen fibrils comprise 15% of the volume .\nthe majority of cells in zone 2 are fibroblasts , with endothelial cells being most of the remainder .\nzone 3 has the highest volume of collagen fibrils and fibroblasts among all the three zones .\nthe morphology of fibroblasts is variable across the three zones ( figure 2 ) . \nit is thicker , more vascular , active , and loosely attached as compared to adults where it is thinner , less active , and firmly adherent . in all age groups , the cells of the periosteum\nretain the ability to differentiate into fibroblasts , osteoblasts , chondrocytes , adipocytes , and skeletal myocytes .\nthe tissues produced by these cells include cementum with periodontal ligament fibers and bone . \nthe periosteum has a rich vascular plexus and is regarded as the umbilical cord of bone .\nthe vasculature system of the periosteum was first studied in detail by zucman and later by eyre - brook .bourke 's studies showed that the capillaries supplying blood to bone reside within the cortex linking the medullary and periosteal vessels ; a recent study has even shown that periosteal cells release vascular endothelial growth factor which promote revascularization during wound healing .\nrecently , studies have reported the existence of osteogenic progenitors , similar to mesenchymal stem cells ( mscs ) , in the periosteum [ 12 , 13 ] . under the appropriate culture conditions ,\nthe periosteum can be easily harvested from the patient 's own oral cavity , where the resulting donor site wound is invisible .\nowing to the above reasons , the periosteum offers a rich cell source for bone tissue engineering ; hence , the regenerative potential of periosteum is immense .\ndeveloping bone substitutes for bone defect repair has inspired orthopedic surgeons , bone biologists , bioengineering researchers to work together in order to design and develop the promising products for clinical applications .\nduhame in the year 1742 can be considered the first investigator to study the osteogenic potential of periosteum and published his findings in the article sur le development et la crueded os des animaux .\na century later , another french surgeon , ollier , discovered that the transplanted periosteum could induce de novo bone formation .\none of the earliest experimental studies to demonstrate osteogenic potential of periosteum was that of urist and mclean who reported that periosteum produced bone when transplanted to the anterior chamber of the eye of the rat .\nskoog subsequently introduced the use of periosteal flaps for closure of maxillary cleft defects in humans ; he reported the presence of new bone in cleft defects within 36 months following surgery .\nsince then , surgeons have reported the successful use of maxillary periosteal flaps [ 18 , 19 ] as well as periosteal grafts from the tibia or rib .\nmelcher observed that new bone is laid down in parietal bone defects of rats and was deposited by periosteum that had not been previously elevated or disturbed in any other way , while other investigators have suggested that the contact between the periosteal flap or graft and the underlying bone is crucial to stimulation of osteogenesis [ 21 , 22 ] .\nmore recently , the osteogenic / chondrogenic capacity of periosteum and related mechanisms have been confirmed , and the underlying biology is better understood through a number of studies [ 2340 ] . \nvarious research papers have been published explaining the osteogenic potential of human periosteal grafts [ 41 , 42 ] .\nthe use of periosteum as a gtr has been suggested by many studies [ 4346 ] , although long - term results are still awaited to establish the regular and the most effective use of periosteal grafts as barrier membranes .\nthe need for a graft , which has its own blood supply , which can be harvested adjacent to the recession defect in sufficient amounts without requiring any second surgical site and has a potential of promoting the regeneration of lost periodontal tissue is a long - felt need .\nthe adult human periosteum is highly vascular and is known to contain fibroblasts and their progenitor cells , osteoblasts and their progenitor cells , and stem cells . in all the age groups , the cells of the periosteum retain the ability to differentiate into fibroblasts , osteoblasts , chondrocytes , adipocytes , and skeletal myocytes .\nthe tissues produced by these cells include cementum with periodontal ligament fibers and bone ; in addition the presence of periosteum adjacent to the gingival recession defects in sufficient amounts make it a suitable graft . \nrecent papers published have shown promising results with the use of periosteum in the treatment of gingival recession defects ( figure 3 ) [ 47 , 48 ] ; moreover , with the advancement in tissue engineering techniques the periosteal derived stem cells have been grown effectively to reconstruct lost tissues .\nperiosteum - derived progenitor cells may serve as an optimal cell source for tissue engineering based on their accessibility , ability to proliferate rapidly , and capability to differentiate into multiple mesenchymal lineages .\nthe periosteum is a specialized connective tissue that forms a fibrovascular membrane covering all bone surfaces except for that of articular cartilage , muscle , and tendon insertions and sesamoid bones .\ncells residing within the periosteum may be excised from any number of surgically accessible bone surfaces ; in addition , when properly stimulated , the periosteum has the potential to serve as a bioreactor supporting a dramatic increase in the progenitor cell population over the course of a few days .\nfurther , once the cells are removed from the periosteum , they have the potential to proliferate at much higher rates than bone marrow , cortical bone , or trabecular bone - derived progenitor cells . \nin addition to their robust proliferation aptitude , it is well established that periosteum - derived progenitor cells have the potential to differentiate into both bone and cartilage .\nfurther , their potential for regenerating both bone and cartilage constructs is superior to that of adipose - derived progenitor cells and comparable with that of bone marrow - derived mesenchymal stem cells .\na recent study by de bari et al . indicates that periosteal progenitor cells are able to differentiate not only into bone and cartilage cells but also into adipocyte and skeletal myocyte cells .\nthere is a growing requirement for dentists to regenerate alveolar bone as a regenerative therapy for periodontitis and in implant dentistry .\nconcerning the donor site , it is easier for general dentists to harvest periosteum than marrow stromal cells , because they can access the mandibular periosteum during routine oral surgery ; also the regenerative potential of periosteum has been effectively used in osteodistraction which has the benefit of simultaneously increasing the bone length and the volume of surrounding tissues .\nalthough distraction technology has been used mainly in the field of orthopedics , early results in humans indicated that the process can be applied to correct deformities of the jaw .\nthese techniques are now utilized extensively by maxillofacial surgeons for the correction of micrognathia , midface , and fronto - orbital hypoplasia in patients with craniofacial deformities .\nthe use of periosteum can revolutionize the success of various dental treatments which require either bone or soft tissue regeneration ; particularly the future use of periosteum must be explored in periodontal and implant surgical procedures . although the regenerative potential of periosteum has been proved by numerous studies , till date the use of periosteum - derived grafts has still not become a standard tool in the armamentarium of dental surgeons , and it may still need some time , and further research before the full regenerative potential of periosteum is utilized .", "answer": "the ultimate goal of any dental treatment is the regeneration of lost tissues and alveolar bone . under the appropriate culture conditions , periosteal cells secrete extracellular matrix and \n form a membranous structure . \n the periosteum can be easily harvested from the patient 's own oral cavity , where the resulting donor site wound is invisible . \n owing to the above reasons , the periosteum offers a rich cell source for bone tissue engineering ; hence , the regenerative potential of periosteum is immense . \n although the use of periosteum as a regenerative tool has been extensive in general medical field , the regenerative potential of periosteum is highly underestimated in dentistry ; therefore , the present paper reviews the current literature related to the regenerative potential of periosteum and gives an insight to the future use of periosteum in dentistry .", "id": 685} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncancer is the second leading cause of death worldwide , accounting for about 600,000 deaths in the united states in 2012 . despite significant improvements in treatment ,\nearly detection remains the most important prognostic factor predicting of better outcome [ 24 ] .\ncurrent cancer screening methods , including mammography for breast cancer , colonoscopy for colon cancer , computed tomography for lung cancer , prostate - specific antigen for prostate cancer , and papanicolaou stains for cervical cancer , have demonstrated some limitations in terms of sensitivity , specificity , complexity , cost , and compliance .\nserum tumor - associated antigens ( taas ) have been extensively studied for early cancer detection because of the simplicity and reliability of the tests used for their determination , such as western blot and enzyme - linked immunosorbent assay ( elisa ) .\nunfortunately , they are transiently secreted and rapidly eliminated from blood circulation [ 6 , 7 ] and usually reach a detectable concentration only in advanced stage of the disease .\nalong with taas , autoantibodies are frequently detected in sera from patients affected by different types of neoplasms .\nthis finding has been interpreted as an attempt of the immune system to block invasion and spreading of cancer cells in the organism .\ncirculating autoantibodies have biological and biochemical characteristics that render them particularly suitable to screen subjects at cancer risk .\nin fact , they may develop early in the process of tumorigenesis , when premalignant or malignant cells begin to express altered molecules as a result of cell transformation [ 10 , 11 ] . in addition , they can easily be detected in the serum because of the usual high concentration and long - time stability . for these reasons ,\ngreat efforts have been made in recent years to identify circulating autoantibodies directed against cancer - related proteins in order to build up tests for the early detection of neoplastic disease [ 1215 ] . in this study\n, we investigated the production of autoantibodies against lectin galactoside - binding soluble 3 binding protein ( lgals3bp ) in patients affected by different types of cancer .\nlgals3bp , also known as 90k or mac-2 bp , has been largely regarded as a taa , since it is present at elevated concentrations in the blood of cancer patients and is overexpressed in the vast majority of cancer tissues .\nboth high serum and tumor levels of lgals3bp have been associated with a poor outcome in patients with different types of neoplasms [ 1821 ] .\nin fact , it can bind important molecules associated with the membrane of tumor cells , such as galectin-3 , galectin-1 , and 1-integrins [ 16 , 22 , 23 ] .\nadditionally , lgals3bp can interact with extracellular matrix proteins such as collagen , fibronectin , and laminin [ 23 , 24 ] . here\nwe show that patients with different types of cancer , but not healthy subjects , develop autoantibodies against lgals3bp .\nthis finding discloses the capability of lgals3bp to trigger a humoral immune response in cancer patients and provides the basis for further investigation on a possible use of anti - lgals3bp antibodies as biomarkers for early diagnosis of cancer .\nthe study population consisted of 71 patients with different types of cancers , 15 gastrointestinal cancers , 13 non - small - cell lung cancers ( nsclc ) , 12 breast cancers , 10 neuroendocrine tumors ( net ) , 10 urogenital tract cancers , 7 melanomas , and 4 others ( 2 gliomas , 1 tongue cancer , and 1 osteosarcoma ) .\nserum was collected from total blood and stored at 20c after adding 0.01% sodium azide .\nhuman recombinant lgals3bp was immunoaffinity - purified from serum - free supernatant of human embryonic kidney ebna-293 cells ( invitrogen , carlsbad , ca , usa ) transfected with lgals3bp cdna . \nninety - six well microtiter plates ( nalge nunc , denmark ) were coated with recombinant purified lgals3bp protein ( 5 g / ml in pbs ) at 4c overnight .\nthe plate was saturated with 1% bsa and 0.05% tween-20 in pbs ( saturation buffer ) at 37c for 2 h and then incubated with 100 l of serum from healthy donors or patients at 37c for 1 h. the serum was diluted 1 : 100 in saturation buffer .\nafter 3 washes with 0.05% tween-20 in pbs ( washing buffer ) , a second incubation was performed with 100 l of biotin - conjugated anti - human igg ( sigma , st louis , mo , usa ) , diluted 1 : 2000 in saturation buffer , at 37c for 1 h. after washing , a third incubation was performed with peroxidase - conjugated extravidin ( sigma , st louis , mo , usa ) diluted 1 : 4000 in saturation buffer , at 37c for 45 min .\nafter washing , 100 l of tmb substrate was added to each well and the plate was shaken at room temperature for 15 min .\neventually , the reaction was stopped by adding 100 l of 1 m h2so4/well and color revealed by reading absorbance at 450 nm in an automatic elisa reader . to measure serum concentration of lgals3bp a commercially available elisa kit ( diesse , siena , italy )\npurified human recombinant lgals3bp ( 10 g / well ) was separated by 8% sds - page under reducing conditions and transferred to nitrocellulose using standard procedures .\nmembrane was saturated in blocking buffer phosphate buffered saline with 0.05% tween-20 ( pbs - t ) , 5% low - fat milk , 1% bsa and at 4c overnight . after washing in pbs - t\n, membrane was incubated with serum from controls or patients affected by cancer , diluted in an equal volume with pbs - t , at room temperature for 1 h. after washing in pbs - t , membrane was incubated with biotinylated anti - human igg ( sigma , st louis , mo , usa ) diluted 1 : 1000 in blocking buffer at room temperature for 1 h and then with extravidin peroxidase ( sigma , st louis , mo , usa ) 1 : 500 in blocking buffer for 30 min . to identify the presence of antibodies bound to lgals3bp , the colorimetric substrate dab ( 3,3-diaminobenzidine )\neach sample was assayed in triplicate and the mean value was used for statistical analyses .\nthe normal upper cut - off value of anti - lgals3bp antibody in sera was set at the value of the mean + 2sd of the absorbance in 54 healthy donors .\ndifferences in the proportion over the cut - off limit were evaluated by fisher 's exact test .\npatients affected by different types of cancers showed significant increased levels of lgals3bp autoantibodies ( p < 0.001 ) compared to healthy subjects ( figure 1(a ) ) .\nthe specific binding of antibodies to lgals3bp was confirmed in western blot , where the presence of anti - lgals3bp igg was detected as two bands at about 97 kda and 66 kda , the exact size of the protein in its full length and cleaved form , respectively ( figure 1(b ) ) . among patients ,\nnsclc , gastrointestinal cancer , urogenital tract cancer , and net reached the highest levels of autoantibodies , while there was no significant increase in breast cancer and melanoma ( table 2 ) . setting the normal upper cut - off limit of elisa at od 0.99 ( the mean + 2sd of the absorbance in sera from healthy individuals ) ,\nthe assay showed a sensitivity of 33% ( 26/71 patients were positive ) and a specificity of 98% ( only 1 out of 54 controls was positive ) .\nall cancer groups , but melanoma , showed autoantibody levels significantly above the cut - off limit ( table 2 ) .\nas expected , the protein was significantly higher in patients with cancer compared to normal subjects ( 13.19 versus 6.36 g / ml , p < 0.001 ) ( table 3 ) , but values did not correlate with the levels of autoantibodies ( data not shown ) .\nusing elisa technique , we show that lgals3bp is able to elicit host immune response with igg autoantibodies production in patients affected by different types of cancer .\nanti - lgals3bp igg concentrations were higher in patients with nsclc , gastrointestinal cancer , urogenital tract cancer , and net than in those with breast cancer and melanoma , but the number of patients in each subgroup was insufficient to yield a statistically reliable comparison . \nit is generally accepted that tumor proteins perceived as nonself by the immune system and able to trigger an immune response are often overexpressed , mutated , misfolded , or endowed with posttranslational changes , such as alterations of glycosylation and phosporylation [ 28 , 29 ] .\nconsistently , lgals3bp may evoke autoantibody production because it is overexpressed in cancer cells , and also because it may carry posttranslational alterations in its glycidic moiety .\nqualitative and quantitative changes in o- and n - glycosylation of proteins are frequent events in malignancies [ 30 , 31 ] and differences in the glycosylation pattern of lgals3bp have been reported in some cancer cell lines .\nfinalistically , antitumor directed antibodies are generated in order to halt tumor initiation and progression . as this process initiates early in cancerogenesis , in a preclinical phase of the disease\n, autoantibodies production has been considered a useful biomarker for early cancer diagnosis [ 3235 ] . in this study ,\nthe serum levels of anti - lgals3bp igg detected in cancer patients were not correlated with those of lgals3bp , indicating that even small amount of the protein , as expected in the initial phase of cancer growth , may generate high concentrations of autoantibodies .\nthis evidence suggests a possible role for anti - lgals3bp igg in the early detection of cancer .\nalthough it is not possible to exclude that the presence of autoantibodies might affect the correct quantification of lgals3bp by elisa , the identification of anti - lgals3bp igg in western blot indicates that the epitopes recognized by these autoantibodies are different from those recognized by the antibody used in elisa .\nin fact , western blot performed under reducing conditions can detect only autoantibodies directed to epitopes expressed on the primary structure of lgals3bp , while the monoclonal antibody contained in the commercially available elisa kit , known as sp2 , recognizes a conformational epitope shaped in the native form of the protein and , for this reason , is not suitable for western blotting . in cancer patients ,\nautoantibodies are frequently directed against cellular proteins that play key roles in tumor progression , including molecules involved in cell cycle , signal transduction , proliferation , and apoptosis [ 3638 ] . as a consequence ,\nthe identification of the molecular target of autoantibodies might be of relevance in designing new antitumor agents .\nwe can , therefore , speculate that lgals3bp could be a candidate for targeted therapies against cancer . in the past few years\n, the growing interest in autoantibodies as a possible tool for the early diagnosis of cancer and the identification of new targets for molecular therapy has made the development of high - throughput techniques such as serex ( serological analysis of tumor antigens by recombinant cdna expression cloning ) , phage display , protein microarray , serpa ( serological proteome analysis ) , and mapping ( multiple affinity protein profiling ) able to detect simultaneously multiple autoantibodies and their cognate taas . with these methods ,\nseveral new targets have been identified , but collectively single antigens have shown low sensitivity and specificity to be used in clinical screening . to increase sensitivity ,\nautoantibody diagnostic tests combining two or more taas [ 4143 ] or evaluating well - known biomarkers in combination with autoantibodies have been developed .\nfor example , a large screening study of high - risk individuals for lung cancer has validated a test measuring autoantibody levels against a panel of six taas ( p53 , ny - eso-1 , cage , gbu4 - 5 , annexin 1 , and sox2 ) . in another study ,\nthe combination of p53 autoantibodies and ca125 levels increased sensitivity for ovarian cancer from 73.8% ( ca125 ) to 85.7% ( ca 125 plus p53 autoantibodies ) .\nthe determination of anti - lgals3bp igg presented in this study showed a very high specificity ( 98% ) , but a low sensitivity ( 33% ) , comparable to that reported for autoantibodies against single taa , ranging between 10% and 30% .\ntherefore , our anti - lgals3bp elisa lacks sufficient sensitivity to be used in early cancer diagnosis .\nnevertheless , the determination of autoantibodies against lgals3bp might be useful to increase the sensitivity of tests combining multiple autoantibodies .\npreliminary results indicate that using a set of different autoantibodies combined with autoantibodies for lgals3bp will increase the sensitivity for breast cancer patients to 50% and maintain the high specificity ( 98% ) .\nthese preliminary results should be tested for other types of cancers as well . in summary ,\nour study demonstrated the presence of autoantibodies against lgals3bp in the serum of patients with different types of cancers .\nthese autoantibodies may be used in developing screening tests for early - stage cancer detection .", "answer": "purpose . \n circulating autoantibodies have been extensively investigated as possible markers for early diagnosis of cancer . \n the present study was carried out to investigate whether anti - lgals3bp igg autoantibodies could be classified as a biomarker for malignant tumors . \n methods . an in - house developed enzyme - linked immunosorbent assay was used to detect autoantibodies to lgals3bp in sera from 71 patients with various types of cancers and 54 healthy subjects matched by age and gender . \n results . \n patients with cancer have significant higher circulating levels of anti - lgals3bp antibodies as compared to control subjects ( p < 0.001 ) . \n the test has a sensitivity of 33% and a specificity of 98% . conclusions . \n anti - lgals3bp igg autoantibodies are a promising biomarker for malignant tumors and could play a role in the development of a multimarker assay for the early detection of cancer .", "id": 686} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nstruma ovarii is an ovarian teratoma , represented in more than 50% by thyroid tissue .\nfive percent of struma ovarii cases have been proven to be malignant and , as in the thyroid gland , papillary thyroid carcinoma is the most common histotype arising in struma ovarii . because of the unusual occurrence of this tumor , its management and follow - up after pelvic surgery is still controversial .\nusually , total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii , while these procedures are still controversial in non - metastatic thyroid cancer arising in struma ovarii .\nwe report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii . after pelvic surgery , thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered .\nradioiodine - ablation of residual thyroid tissue was performed and levothyroxine mildly - suppressive treatment was started .\na more aggressive treatment should not be denied for malignant struma ovarii without any evidence , even when apparently confined into the ovary .\nhowever , in selected cases , aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow - up .\ngerm cell tumors represent 15 - 20% of ovarian cancers and most of them are mature cystic teratomas ( 1 ) .\nstruma ovarii is a highly specialized ovarian teratoma , chiefly represented by thyroid tissue ( 2 ) .\nin fact , while 5 - 15% of teratomas contains small foci of thyroid tissue , this latter should represent more than 50% in a struma ovarii ( 1 ) .\napproximately , 5% of struma ovarii has been proven to be malignant and metastases are uncommon ( 2 )\n. fairly good prognosis characterizes these patients : survival rate of patients in follow - up at 5 , 10 and 25 years is 92% , 85% and 79% , respectively ( 3 ) .\nlong - term follow - up is recommended in all cases ( 4 ) . as in the thyroid ,\npapillary carcinoma is the most common malignant histotype ( 70% , 1/3 represented by its follicular variant ) arising in struma ovarii ; while follicular carcinoma is observed in the remaining 30% ( 3 - 5 ) .\nmalignant struma ovarii generally occurs in patients in the fifth and sixth decades of life ( 5 ) , it is unilateral ( 94% ) and more frequently involves the left ovary ( 3 , 5 ) .\nfunctional thyroid alterations are unusual and overt hyperthyroidism is reported in 5 - 8% of cases ( 5 ) .\nthe most common clinical presentation of struma ovarii is a pelvic mass ( 3 ) ; lower abdominal pain , abnormal vaginal bleeding or menstrual irregularities and ascites may be associated ( 5 ) .\nhowever , the tumor is often unexpectedly diagnosed during abdominal / pelvic ultrasound or surgery ( 3 , 5 ) . abdominal hysterectomy and bilateral salpingo - oophorectomy with omentectomy\nunilateral salpingo - oophorectomy is the preferred treatment for women who require preservation of fertility .\nbeing this tumor fairly uncommon , there is a lack of diagnostic and treatment guidelines ( 4 , 6 - 8 ) .\nafter initial surgery , some authors suggest that the management of malignant struma ovarii may be similar to that of other germ cell tumors ( 1 ) ; other authors suggest , as in differentiated cancer of thyroid gland management , to perform a thyroidectomy followed by radiotherapy with 131 isotope of iodine ( rai ) ( 9 ) and levothyroxine suppressive therapy ( 3 , 4 , 7 , 8) , although restricted to patients with recurrence or residual disease ( 2 , 4 , 5 ) .\nno consensus has been reached in performing prophylactic total thyroidectomy and the treatment strategy for nonmetastatic malignant disease remains controversial .\nwe present a case of 30-year - old female with follicular variant of papillary thyroid carcinoma arising in struma ovarii and concomitant differentiated cancer of thyroid gland .\na 30-year - old woman was admitted to the emergency room because of persistent abdominal pain in the right side , appeared some day before , during a shift work as agricultural laborer .\nan accurate medical history ascertained that she had an increased steady weight ( 109 kg ; bmi = 40 kg / m ) , but she was in apparently good health also showing customary appetite and regular menses , before the appearance of pain . physical examination revealed the presence of a large mass , palpable in hypogastric region and in right lower abdominal quadrant .\nto better define the diagnosis , the physician required blood sampling for routine tests , gynecological counseling and an abdominal computer tomography ( ct ) .\nthe abdominal ct confirmed the presence of a mass measuring 10 x 6 cm , in the right ovary .\nin particular , an ovariian cyst ( 7 , 3 x 3 cm ) along with a portion of the fallopian tubes of 4 cm and the vermiform appendix were removed .\nperitoneal washing and multiple peritoneal biopsies in nearby areas ( douglas , bladder , bilateral paracolic gutter , and diaphragm ) were also performed .\nhistological examination revealed the presence of a follicular variant of papillary thyroid carcinoma ( 0.9 cm ) harbored in a mature teratoma .\nthe cancer was localized and the right ovary capsule was not infiltrated by the tumor . based on union for international cancer control ( uicc ) 2002 ,\nappendix showed the features of chronic follicular inflammation and the remaining tissues were disease - free .\nafter surgery , functional examination of thyroid gland revealed serum iodothyronines levels in the normal range , thyroid ultrasonography showed a normal glandular volume with patchy echo - structure and , in the left thyroid lobe , the presence of a 23 , 4 x 14 x 9 mm hypoechogenic nodular lesion . an ultrasound assisted fine needle aspiration of this thyroid lesion was performed and cytological examination showed the presence of dense colloid in particles and small groups of thyrocytes with notes of oxyphilic metaplasia and anisonucleosis ; this sample was classified as follicular lesion with oxyphilic cells of undetermined significance ( category iii according to the bethesda system , 2009 ) ( 10 ) . so far , in presence of follicular lesion and for an appropriate follow - up of papillary carcinoma arising in struma ovarii , the patient underwent total thyroidectomy ( 11 , 12 ) .\nhistological examination revealed that the nodule examined in the left lobe was benign , but showed a papillary micro - carcinoma in the right lobe ( diameter = 0.2 cm ; pt1a ) within a hyperplastic thyroid characterized by abundant oxyphil cells .\nthe ablation of residual thyroid tissue was performed by a dose of 30 mci of 131i according to meas et al .\nwhole body scan after therapeutic dose showed two focal areas of strong uptake in the anterior region of the neck , in right superior paramedian and left inferior paramedian areas , due to minimal glandular remnants ; no area of uptake in the pelvis or elsewhere was notice .\nmu / l and serum thyroglobulin ( tg ) was 1.24 mg / dl , in the absence of anti - thyroglobulin antibodies ( anti - tgab ) .\nlevothyroxine treatment was started ( 1.6 g / kg / day ) and thyroid hormones and tsh were evaluated after four months .\nsix months after total thyroidectomy , patient underwent neck ultrasonography and tg evaluation , which showed no evidence of recurrences .\npatient is up to now in follow - up for both struma ovarii and differentiated thyroid cancer according to european thyroid association guidelines ( 12 ) .\nfirst described at the end of 21th century , struma ovarii is a rare tumor representing less than 1% of all ovarian tumors ( 6 , 14 ) and 2.7% of all dermoid tumors ( 6 ) .\na diagnostic and therapeutic characterization of struma ovarii is needed as it may harbor a differentiated thyroid cancer ( 1 ) .\nmalignant struma ovarii has been , in fact , replaced with the more appropriate \n( tcaso ) , namely when histological features support the existence of a well - differentiated thyroid carcinoma ( 3 , 14 , 15 ) .\nmolecular evidence that malignant struma ovarii and differentiated thyroid cancer may share similar pathogenic events ( 3 , 16 ) has been presented .\napproximately 70% of follicular cell - derived thyroid carcinomas are associated with activating mutations of braf , ras , ret and ntrk1 ( 3 , 4 , 16 ) .\nbraf mutations have been described in 29 - 69% of primitive papillary thyroid cancer and in particular v600e missense mutation type is the most common alteration in sporadic papillary carcinoma ( 3 , 17 ) . also in four out of six malignant struma ovarii and in none of nine benign struma ovarii , braf mutations were observed in the schmidt s study ( 3 , 4 ) .\nthe concurrent presence of the same genetic alteration ( i.e. braf mutations ) , in thyroid neoplasia and in struma ovarii would be intriguing in that it may support the hypothesis of a multifocal thyroid neoplasia in two distant sites ( 13 , 16 ) .\nautonomous histopathological criteria have not been established for thyroid carcinoma arising in struma ovarii and , so far , the diagnosis of malignant struma ovarii follows the guidelines for the diagnosis of primary thyroid carcinoma ( 3 ) .\nevidence also indicates that patients with malignant struma ovarii should be treated as those having differentiated cancer in the thyroid gland ( 3 , 10 ) . in patients with thyroid cancer confined to the ovary\n, pelvic surgery has been considered sufficient and prophylactic thyroidectomy not recommended ( 1 , 2 , 14 ) ; in these patients follow - up ensues as in non - aggressive dtc ( 1 , 14 ) .\nfine needle aspiration cytology has been considered appropriate when thyroid nodular lesions would have been detected at ultrasound ( 1 , 4 , 14 ) .\nnoticeably , however , a thyroid carcinoma concurrent with malignant struma ovarii is increasingly detected ( 14 , 18 ) and the treatment of this association is , as yet , not properly defined .\nin fact , a more extensive treatment , e.g. total thyroidectomy and rai , after pelvic surgery , is only recommended for malignant struma ovarii with extra - ovarian spread or distant metastasis ( 1 - 3 ) . in patients with extra - ovarian or metastatic disease\n, evidence suggests that radioiodine ablation and thyrotropin suppression are associated with increased disease - free survival ( 3 , 7 ) . according to another study ,\npatients who underwent total thyroidectomy and radio ablation after pelvic surgery were free of recurrence even after 36 years ( 7 , 8) . on the contrary ,\na recurrence rate of 50% was associated with the conservative treatment of patients ( 8) . moreover ,\na delayed appearance of distant metastasis has been described three years after the treatment in patients with struma ovarii who underwent pelvic surgery alone ( 18 ) . a not negligible fraction ( 6% ) of patients with longer\nfollow up , developed distant metastases after one , three and seven years ( 15 ) .\ntwo - thirds of metastasis occurred at the time of disease recurrence , rather than at first presentation ( 7 ) ; in fact , a number of cases were diagnosed as malignant only following the detection of metastatic recurrences ( 7 ) . in this clinical case\nhigh prevalence of occult thyroid papillary microcarcinoma has been described in autoptic studies ( 36% ) and/or following surgery for benign conditions ( 2 - 24% ) ( 19 ) . however\n, some of these microcarcinomas may represent more aggressive varieties of disseminated tumor cells ( dtcs ) ( 17 ) .\nindeed , papillary microcarcinoma , although infrequently , may show significant differences in clinical behavior , sometimes being very aggressive , despite small primary tumor size ( 17 ) .\n( 13 ) , the contemporary presence of two possibly related thyroid cell - derived tumors , although with low risk stratification , may be considered as a multifocal expression of the same pathogenic alteration .\nthey suggested that a threshold of more than one centimeter as sum of all foci may require a more cautious seeking of thyroid tissue lesions ( 13 ) .\nin this view , american thyroid association guidelines ( 20 ) concerning dtc follow - up should be reinterpreted as being the struma ovarii and papillary carcinoma ( any size ) a multifocal expression of the same tumor . in conclusion\n, a treatment including thyroidectomy followed by radioablation should not be denied a priori , but in selected cases may be advisable to decrease the risk of recurrence and to allow an accurate follow - up ( 7 ) .", "answer": "introduction : struma ovarii is an ovarian teratoma , represented in more than 50% by thyroid tissue \n . five percent of struma ovarii cases have been proven to be malignant and , as in the thyroid gland , papillary thyroid carcinoma is the most common histotype arising in struma ovarii . because of the unusual occurrence of this tumor , its management and follow - up after pelvic surgery is still controversial . \n usually , total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii , while these procedures are still controversial in non - metastatic thyroid cancer arising in struma ovarii.case presentation : we report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii . \n after pelvic surgery , thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered . \n the patient underwent total thyroidectomy and histological examination showed a papillary carcinoma . \n radioiodine - ablation of residual thyroid tissue was performed and levothyroxine mildly - suppressive treatment was started.conclusions:a more aggressive treatment should not be denied for malignant struma ovarii without any evidence , even when apparently confined into the ovary . \n however , in selected cases , aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow - up .", "id": 687} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nleft - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery .\nwe report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection\nthe patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries .\nthe embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed .\nunexpected vascular anomalies may increase the risk of hemorrhage and necessitate conversion to open nephrectomy .\nwe report the case of a major inferior vena cava ( ivc ) anomaly encountered during laparoscopic nephrectomy and discuss its embryogenesis and management .\ncomputed tomography revealed a 4-cm enhancing lesion located centrally within the left kidney ( figure 1 ) .\nlaparoscopic left radical nephrectomy was planned and upon hilar dissection , the ivc was encountered without visualization of the aorta , confirming its left - sided orientation .\nin addition , 3 renal veins were noted , as was a left gonadal vein that drained directly into the ivc ( figure 2 ) . an aberrant vein was exposed that bridged the gonadal vein and the most caudal of the supernumerary renal veins .\nprior to dissection of the renal artery , the caudal renal vein , gonadal vein , and bridging anomalous vein were ligated and transected .\nabdominal ct scan illustrates the ivc as it courses from the normal anatomic position to the left - sided position : ( a ) ivc in right - sided anatomical position ( thick arrow ) ; ( b ) ivc crossing anterior to the aorta ( thick arrow ) ; ( c ) ivc crossing anterior to the aorta ( thick arrow ) and main left renal vein ( thin arrow ) . left renal mass\nis noted in a central location ; ( d ) ivc in left - sided position ( thick arrow ) and second left renal vein ( thin arrow ) .\nview of cephalad ( left ) and caudad ( right ) aspect of ivc ; kidney ( out of frame ) is located towards top of image . left gonadal vein drains into the left - sided ivc .\ntwo of the 3 left renal veins are noted . bridging vein between the main renal vein and gonadal vein is noted .\nthe laparoscopic approach has become an accepted standard for extirpative renal surgery , with less postoperative pain , decreased hospital stay , and shorter convalescence compared with that of open surgery .\ncolombo et al reported that hemorrhage continues to be the most common intraoperative complication of laparoscopic surgery , occurring at a rate of 2.3% and requiring open conversion in 0.9% of cases .\npreoperative knowledge of pertinent vascular anatomy is essential during laparoscopic renal surgery to avoid potential complications . to our knowledge , this is among the initial reported cases of a left - sided inferior vena cava encountered during laparoscopic radical nephrectomy .\nleft - sided ivc is an abnormality that occurs at a prevalence of 0.2% to 0.5% and is usually asymptomatic .\nalthough commonly an incidental finding , it becomes clinically significant when it is mistaken for paraaortic lymphadenopathy or the main renal vein .\nthe embryonic development of ivc involves the emergence and selective regression of 3 pairs of embryonic veins : the posterior cardinal , subcardinal , and supracardinal veins .\nanomalies of the postrenal segment of the ivc include retrocaval ureter , duplicated ivc , and left - sided ivc .\na left - sided ivc is caused by persistence of the left supracardinal vein with regression of the right supracardinal vein .\nthe left subrenal ivc then joins the left renal vein and crosses anterior to the aorta where it unites with the right renal vein . as a result ,\nrenal venous development results from anastomosis of the subcardinal and supracardinal veins . during normal development ,\nmultiple persisting renal veins is the most common anomaly of the venous developmental system with a prevalence ranging from 9% to 20% .\nthe main clinical significance of this finding is the risk of iatrogenic injury during renal surgery .\nwhen a left - sided ivc is encountered , the surgeon must be suspicious of other anomalies . in our patient , 3 renal veins ,\ncareful examination of preoperative radiographic imaging is mandatory in the diagnosis of a left - sided ivc .\ncase reports have described this phenomenon during laparoscopic live donor nephrectomy without adverse effects . in our experience\n, this anomaly may be more readily apparent when evaluating patients with higher resolution imaging .\nin accordance with other reports , our case demonstrates that laparoscopic radical nephrectomy can be successfully performed without complications in the presence of a left - sided ivc .", "answer": "background : left - sided inferior vena cava ( ivc ) is an unusual abnormality that may be clinically significant during renal surgery.methods:we report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy . during the hilar dissection , unusual vascular anatomy was encountered . \n the patient was noted to have a left - sided inferior vena cava with multiple renal veins and anomalous tributaries . \n laparoscopic radical nephrectomy was performed without complication.discussion:the embryology of a left - sided inferior vena cava is reviewed , and the safety and feasibility of a laparoscopic approach is discussed .", "id": 688} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhumans are infected naturally by 3 species of hookworms ; necator americanus , ancylostoma duodenale , and ancylostoma ceylanicum .\nindividual people can be infected with 1 species , 2 species , or all 3 species of hookworms [ 1 - 5 ] . although a. ceylanicum is often considered to be a zoonotic pathogen , since it is also found in dogs and cats , its importance as a significant soil - transmitted helminth of humans is increasingly being recognized .\ntwo haplotypes of a. ceylanicum have been identified ; one largely found in humans and another that infects humans , dogs , and cats .\na. ceylanicum is considered to be of emerging importance as a helminth of humans in the asia pacific region .\na fourth hookworm also reported from humans , ancylostoma caninum represents a canine species with zoonotic potential .\nthis species has mainly been recorded as causing eosinophilic enteritis in people in tropical australia , but never establishes a patent infection and hence humans are regarded as accidental hosts .\nhuman hookworm is common in the solomon islands , with an estimated 192,000 people ( 36% of the population ) infected , but the different species involved are yet to be determined [ 9 - 11 ] .\nthe report to the rockefeller hookworm campaign in 1928 described only n. americanus as being present on these islands .\nthe only previous report of a. ceylanicum from the solomon islands was a 5-year - old boy who imported the species in 1938 from the shortland island group of the solomon islands to australia .\nthe solomon islands is a small pacific nation to the north east of australia , with a predominantly melanesian population .\nthe regional assistance mission to solomon islands ( ramsi ) occurred between 2003 and 2013 , at the request of the solomon island s government , to assist in stabilizing internal troubles occurring within the nation .\nramsi consisted of 2,200 police and soldiers from many pacific island nations and was led by australia .\nthis case report describes the finding of a. ceylanicum in an australian soldier who developed symptomatic disease after returning from a deployment in solomon islands with ramsi .\nthe patient was a 26-year - old male living in townsville , north queensland , australia who presented in march 2004 with central poorly defined abdominal pain of 4 weeks duration and increased frequency of defecation .\na peripheral eosinophilia had been noted on blood tests in february prior to symptom development , and in march , when eosinophils were 6.2010/l whilst red blood cell indices were normal ( hemoglobin 146 g / l , mcv 93 fl , hematocrit 0.44 , red cell count 4.710/l ) .\nthe patient had served with ramsi in the solomon islands from late july to early december 2003 .\nhis duties involved travel to various remote areas and provided multiple opportunities to become infected with hookworms .\nroutine treatment with albendazole had been given by the australian defense force on return to townsville in december , 2 months prior to development of symptoms .\ninitially , in march 2004 no parasite eggs were detected in feces by formalin - ethyl acetate concentration , but infective larvae of hookworms were found on harada - mori culture .\ninfective larvae were sheathed , had inconspicuous buccal spears , the intestine was narrower than the esophageal bulb , and inconspicuous transverse striations were noted on the sheath in the tail region .\nthe infective larvae , measured after preservation in hot formalin , had the following dimensions , meansd ( range ) : length 657.19.6 m ( 633 - 669 m ) , width 21.40.9 m ( 20.2 - 22.2 m ) , esophagus 156.73.5 m ( 151 - 162 m ) , tail 77.93.8 m ( 69 - 81 m ) , length of sheath 763.78.6 m ( 779 - 746 m ) ; esophagus / length 23.80.5% , and tail / length 11.90.6% . due to the failure of single dose post - deployment albendazole therapy to eradicate this infection , the patient was treated with 100 mg of mebendazole twice daily for 3 days .\ntwelve adult hookworms ( 6 females and 6 males ) were recovered by dissection of stools passed during the 48 hr immediately following treatment . the en face view revealed a robust ventral cutting plate bilaterally with a prominent point on the dorsal end and less obvious point on the ventral end ( fig .\nthe width of the bursa in lateral view was greater than its length , and the mediolateral and posteriolateral bursal rays were parallel ( fig .\nthe morphology of the adult hookworms was consistent with a. ceylanicum with key features being : the large ventral cutting plates terminating at the dorsal end in a large single tooth ; and in the male the parallel mediolateral and posteriolateral bursal rays .\nalthough the morphology and dimensions of the infective larvae are more consistent with a. ceylanicum than n. americanus , differentiating them from infective larvae of a. duodenale is unreliable .\nalthough molecular taxonomy is valuable in identifying hookworm species , it was not available in this case and , as the specimen was subsequently accidentally disposed of , molecular taxonomic studies can not be performed now . however , the morphological features were sufficient to identify this species as a. ceylanicum .\nthis represents only the second report of human a. ceylanicum infection having been acquired in this nation , with the first being made almost 80 years ago .\nthis finding not only expands the known range of human a. ceylanicum infection but also raises the question of whether a. ceylanicum is in fact a common cause of human hookworm infection in some regions of the solomon islands , as it has recently been described as being in many parts of asia . the only previous reported description of hookworm species in the country was almost 80 years ago and was anecdotal , not providing descriptions of number of people tested or how the species identifications were arrived at .\na. ceylanicum infection has recently been reported from two people in western australia . prior to this , a. ceylanicum had been reported from dogs and cats in northern australia , including those from townsville .\nhence , the infection could have been acquired in north queensland or while deployed with ramsi .\nthe likelihood of infection with ancylostoma from humans in the solomon islands is high , but negligible in north queensland since human feces are disposed of safely .\nhowever , since a. ceylanicum is present in dogs and cats in north queensland , there is a possibility of a zoonotic australian source even though this infection has not been seen in humans in this region .\nmany ramsi personnel were infected with hookworms during their mission to the solomon islands , and an isolated case of a. ceylanicum infection had been reported from this area early in the 20th century .\nthis adds to the likelihood that the case presented here was acquired in the solomon islands and not elsewhere .\nthe clinical symptoms displayed by our patient were consistent with the phase of hookworm infection during which the host attempts to eliminate the parasite using an allergic response , manifesting morphologically as eosinophilic enteritis . for n. americanus\nthis response begins about 10 days after infection and persists for up to a month .\na. caninum and a. duodenale have a more complicated life cycle in which some infective larvae can enter a state of hypobiosis ( arrested development ) and can orchestrate entry to the intestine to coincide with the wet season and physiological events [ 23 - 26 ] . whether a. ceylanicum has\nthe failure of a routine post - deployment albendazole treatment to eliminate the infection in our patient supports a hypothesis that the current infection was due to hypobiotic larvae activated after the anthelmintic was given .\nacute enteritis has been described previously in soldiers with a. ceylanicum acquired in west papua ( formerly dutch new guinea ) and in a traveller returning from myanmar to france .\ntreatment with albendazole in the latter patient cleared the gut infection but symptoms and parasites recurred after 3 months adding evidence for hypobiosis in a. ceylanicum .\nour patient was treated after diagnosis with mebendazole due to its far greater tissue penetration and therefore greater capacity to kill hypobiotic larvae in the tissue .\nthe key points from this case report are : a. ceylanicum should be considered as a cause of acute eosinophilic enteritis in returned travellers , workers , or defense force personnel who have lived or visited tropical and subtropical countries ; laboratory confirmation may require persistence to make the diagnosis of hookworms and will require special tests ( morphology of adults after treatment ; molecular taxonomy on stools or infective larvae ) to identify the species ; and human infection with a. ceylanicum is probably endemic in the solomon islands and further study of the prevalence of different hookworm species present in this country is warranted .", "answer": "a 26-year - old male member of the australian defense force presented with a history of central abdominal pain of 4 weeks duration and peripheral eosinophilia consistent with eosinophilic enteritis . \n acute hookworm disease was diagnosed as the cause . \n adult worms recovered from feces after therapy with albendazole were morphologically consistent with ancylostoma ceylanicum . \n as the patient had been deployed with the regional assistance mission to solomon islands for 6 months prior to this presentation , it is very likely that the a. ceylanicum was acquired in solomon islands . \n until now , it has been assumed that any ancylostoma spp . recovered from humans in solomon islands \n is a. duodenale . \n however , this case demonstrates that human hookworm infection acquired in the solomon islands could be caused by a. ceylanicum .", "id": 689} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncytomegalovirus ( cmv ) colitis is common among immunocompromised patients who are more prone to opportunistic infections .\nafter the infection of cmv is detected by histology or serology , antiviral treatment is usually chosen initially . since cmv disease\ncan not be diagnosed on clinical symptoms alone , diagnosis and treatment are sometimes delayed . here\n, we report a case of a hemorrhagic cmv colitis that occurred in an immunocompromised patient after a colectomy due to colon cancer and was successfully treated with ganciclovir .\nan 85-year - old woman underwent esophagogastroduodenoscopy and colonoscopy for investigation of anemia . a laterally spreading tumor of the granular type , 85 mm in diameter ,\nalthough magnifying image - enhanced colonoscopy suggested a tubulovillous adenoma , surgical resection , not endoscopic mucosal resection , was chosen because of the size of the tumor . however , as she had a medical history including breast cancer , myocardial infarction , general edema due to chronic renal failure ( oral administration of prednisolone 5 mg / day ) , diverticulosis of sigmoid colon , and bilateral ureteral stent placement due to retroperitoneal fibrosis , she did not want to take medical treatment anymore but to monitor her own condition for a while .\nafter 3 months , she finally agreed to have surgery and was admitted to our hospital .\nthe patient underwent ileocecal resection followed by stapled functional end - to - end anastomosis ( fig .\nthe postoperative course was favorable ; dietary intake and oral drug administration were started on postoperative day 4 and both flatus and stool passed .\nhowever , she had sudden abdominal pain and heavy bloody discharge on postoperative day 11 .\nalthough conservative treatment , including blood transfusion therapy for anemia , was performed initially , there was no improvement after a week .\nin addition to the endoscopic findings , the patent 's immunocompromised state suggested possible cmv colitis . because cmv antigen was confirmed in peripheral blood samples , intravenous antiviral treatment was started from the postoperative day 23 ( ganciclovir , 150 mg / day ) .\nafter 4 days of the treatment , bloody discharge stopped , and at 8 days , improvement of abdominal pain was observed .\nthe antiviral treatment was continued for 2 weeks until the serological confirmation of negative cmv antigen .\nafter improvement of the colitis - related symptoms , the patient was discharged from our hospital .\ncmv infection often develops a latent infection with no signs or symptoms after acute infection .\nalthough most people are exposed to cmv in their lifetime , typically only the patients with weakened immune systems , such as aids , malignancy , organ transplant or bone marrow transplant , and steroid or immunosuppressive treatments , become ill by reactivating cmv and present with cmv pneumonia , gastroenteritis , retinitis , and encephalitis .\ncmv disease is often diagnosed by pathologic and serologic confirmation because clinical symptoms are not specific .\nfurthermore , colonoscopic findings of cmv colitis mimic many conditions , including pseudomembranous colitis , ischemic colitis , ulcerative colitis and crohn 's disease . in our case , as we initially considered the bleeding from the diverticulum or anastomosis , conservative treatment was chosen .\nafter one week of conservative therapy , there was no sign of improvement in bloody discharge ; therefore , we decided to perform colonoscopy .\nwe were hesitant to perform colonoscopy due to our patient having had a colectomy . according to the meta - analysis of cmv colitis in immunocompetent hosts , the highest mortality rates were associated with immune modulating conditions that include 16 patients . of those analyzed ,\n5 patients ( 31.3% ) received colectomy as initial treatment and 8 patients ( 50% ) and 6 patients ( 37.5% ) had coexisting renal failure and diabetes mellitus , respectively . in our case\n, as the patient was given steroids due to chronic renal failure and the colonoscopy revealed the longitudinal ulcer at the anastomosis , we were able to suspect cmv colitis and confirmed the diagnosis serologically .\nbecause endoscopic biopsy was not performed , cmv infection was not evaluated histologically . of note\n, we performed immunohistochemistry of cmv protein using resected colon cancer specimen , though cmv - positive stain was not detected .\nthis result seems to relate with the fact that cmv is not associated with carcinogenesis and reactivation of latent cmv infection causes cmv colitis [ 5 , 6 ] .\nthe first choice of treatment of cmv infection is antiviral therapy [ 7 , 8 ] .\nsystemic antiviral treatment has provided significant advances and has resulted in dramatically improved outcomes [ 7 , 8 ] .\ntreatment time usually ranges from 1 to 4 weeks , depending on the treatment effect such as improvement of the symptoms and/or confirmation of the negative cmv antigen . in our case , despite the necessity of reducing the dose of ganciclovir due to renal failure , the patient showed good response to systemic therapy and did not require further treatment . fortunately , as she did not show uncontrollable heavy bleeding or symptoms of bowel perforation , surgical resection was not needed .\nthe case we mentioned above can potentially occur in immunocompromised patients . with recent progress in medicine\n, the number of high - risk patients who undergo surgery is increasing ; therefore , the reactivation of latent cmv infection in immunocompromised patients should be actively considered for the differential diagnosis , leading to timely diagnosis and appropriate treatment .", "answer": "we report a case of hemorrhagic cytomegalovirus ( cmv ) colitis , occurring in a postoperative patient due to a weakened immune system . \n an 85-year - old woman with a medical history , including chronic renal failure treated with oral administration of prednisolone , underwent colectomy due to an ascending colon cancer . while the postoperative course was favorable , she exhibited acute severe abdominal pain and massive bloody discharge after 11 days of surgery . \n her colonoscopic examination showed multiple longitudinal ulcers on the anastomosis . \n in addition to these endoscopic findings , her past medical history helped suggest cmv colitis . because serological testing revealed positive cmv antigen , she was finally given a diagnosis of cmv colitis and received intravenous ganciclovir for the initial treatment . \n hemorrhagic cmv colitis after colectomy is an important postoperative complication ; we therefore present our case with diagnosis and treatment experience .", "id": 690} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nintraspinal juxtafacet cysts ( commonly , synovial or ganglion cyst ) can be an uncommon cause of lower and radicular pain , neurogenic claudication , and cauda equina syndrome2,9,10,13 ) .\nspinal synovial cysts generally arise from a degenerated facet joint and often presenting as a gradual onset of back pain and potentially , chronic progressive radiculopathy\nis a much less common occurrence , and patients may present with acute onset of symptoms3,13 ) .\nwe describe a case in which hemorrhage into a right l2 - 3 facet synovial cyst caused acute back pain and radiculopathy and required surgical excision .\na 72-year - old - woman with a past history of hypertension presented to the clinic with acute back pain radiating to the anterior surface of the right thigh and leg .\nthe right straight - leg - raise test elicited pain in the leg at 30 which was exacerbated further by ankle dorsiflexion .\nmagnetic resonance imaging ( mri ) revealed the presence of a cystic formation in the right l2-l3 facet joint with arthritis compressing the l3 right root and the dural sac ( fig .\n, the mri displayed a hyperintense abnormality on t1-weighted images and hypointense on t2-weighted images consistent with hemorrhage .\nthe posterior elements from l1 to l3 were exposed and right l2-l3 laminectomy and facetectomy were performed .\na brownish mass was found in continuity with the right l2-l3 facet joint adherent to the dural sac .\nthe extradural hematoma was visualized and evacuated , effectively decompressing the right 2 nerve root and sacral sac .\nmicroscopically , there was a synovial cyst with synovial cell lining , neovascularization , hemosiderin microdeposits , and blood ( fig .\none month after the operation , the patient had no symptoms in her lower back and leg .\nspinal synovial cyst can be defined as a soft tissue mass located extradurally along the medial border of a degenerated facet joint , especially l4 - 5 level1,4,8,11,12 ) .\nthese cysts are filled with clear or xanthochromic fluid and have a synovial - like epithelial lining with a demonstrable connection to a joint capsule3,11 ) .\nif the synovial cell lining and the communication with a joint capsule are absent , the cyst is classified as ganglion11 ) .\nintraspinal synovial cysts are rare but have been documented with increasing frequency because of the improvement of neuroradiological imagings4 ) .\nan mri is considered a good modality for diagnosis . on mri , cysts appear as well - circumscribed , epidural mass lesions that are hypo- and hyper - intense on t1 and t2 weighted images , respectfully . bleeding into a synovial cyst may cause a sudden expansion of the cyst leading to compression of the epidural space result in root compression symptoms .\nhemorrhage into a synovial cyst results in an acute increase in pain and radicular symptoms , including neurological deficits12 ) .\nhemorrhagic presentation can be caused by anticoagulation treatment , trauma , disc herniation , vascular anomaly , and neoangiogenesis in the cyst4 ) .\nin addition , high vascularization of the cyst can cause hemorrhage in spite of minor trauma or just spinal instability .\nsynovial cyst hemorrhagic events in some cases can occur despite the absence of trauma or coagulopathy13 ) . as a result ,\nother yet to be determined risk factors for synovial cyst hemorrhage occurrence exist prompting the need for more studies .\nnon - hemorrhagic synovial cysts are occasionally treated by percutaneous aspiration with successful resolution of symptom6 ) .\nthe injection of corticosteroid agents into the facet joint may be an treatment option . despite conservative treatment , recurrence of cyst with symptoms\nthe natural history of spinal synovial cysts is unknown , but spontaneous remissions of a synovial cyst on follow up imaging with improved symptoms have been reported5 )\nhowever , pain can be treated with steroid injections and bed rest in substantial number of patients .\nwe report of a case in which hemorrhage into a right l2 - 3 facet synovial cyst causing an acute back pain and radiculopathy .\ntreatment by resection of the cyst and evacuation of the hematoma led to complete neurological recovery .\nsynovial cysts of the lumbar spine are an uncommon cause of back and radicular pain .\nrarely , these cysts can go through hemorrhagic transformation by trauma , anti - coagulopathic state , or for unknown reasons .\nhemorrhage into a cyst is an uncommon occurrence that can lead to acute symptom . in most cases , surgery is the treatment of choice for symptomatic hemorrhagic synovial cysts .\nsurgery involving the evacuation of the hematoma and/or cyst can result in complete resolution of acute symptoms and neurologic deficit .", "answer": "synovial cysts of the lumbar spine are an uncommon cause of back and radicular pain . \n these cysts most frequently present as back pain , followed by chronic progressive radiculopathy or gradual onset of symptoms secondary to spinal canal compromise . \n although less common , they can also present with acute spinal cord or root compression symptoms . \n we report of a case in which hemorrhaging into a right l2 - 3 facet synovial cyst caused an acute onset of back pain and radiculopathy , requiring surgical excision .", "id": 691} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe report a case of a patient who presented with a complex open 3c gustilo anderson fracture who subsequently developed flap failure , failed internal fixation complicated with osteomyelitis of the talus .\nthey vary in severity from minor metatarsal / phalangeal fractures to complicated midfoot and hindfoot injuries .\nopen fractures are poorly reported since they are rare and usually treated in specialist trauma centres .\nreported amputation rates in open midfoot fractures are 30% highlighting their severity , coexisting soft tissue compromise , infection and difficulty covering midfoot injuries with flaps . with the midfoot playing a key role in foot function ,\nsoft tissue defects of the foot pose further challenges given the specially adapted architecture to facilitate tendon gliding .\na 55-year - old woman presented with an open 3c gustilo anderson fracture . her medical history included rheumatoid arthritis , osteoarthritis , ischaemic heart disease , diabetes mellitus and asthma .\nsoft tissues were closed using a free flap from the left thigh and a flap from the right lower limb .\nbony injury was treated with open reduction internal fixation with screw fixation of the first and third metatarsals into the talus with restoration of the medial and middle columns achieved using cannulated screws .\nadditional stability was achieved by plate fixation of the medial and lateral columns ( fig .\n( c and d ) radiographs illustrating open reduction internal fixation ( orif ) ( screw fixation of the first and third metatarsals into the talus ) .\nthe orif using cannulated screws allowed restoration of the medial and middle columns of the foot .\n( c and d ) radiographs illustrating open reduction internal fixation ( orif ) ( screw fixation of the first and third metatarsals into the talus ) .\nthe orif using cannulated screws allowed restoration of the medial and middle columns of the foot .\nfour months since the initial presentation , she was readmitted due to foot dorsal flap edge failure for which vacuum - assisted closure was unsuccessful ( fig .\nfigure 2:flap failure on dorsal aspect of foot when patient presented after failed vacuum - assisted closure treatment .\nflap failure on dorsal aspect of foot when patient presented after failed vacuum - assisted closure treatment .\nprimary limb shortening with a talectomy was conducted to reduce the soft tissue deficit and remove infected and necrotic bone , tibiocalcaneal arthrodesis for joint stability using external fixation , and dead space was treated with calcium sulphate mixed with vancomycin and systemic intravenous and oral antibiotics for osteomyelitis postoperatively ( figs 3 and 4 ) .\nthe wound was closed after the external fixator was applied . wound swabs and bone samples revealed enterococcus faecalis and e. raffinosus and diphtheroids .\nthe patient was treated with intravenous teicoplanin and meropenem with oral stepdown to linezolid and ciprofloxacin . \n\n( b d ) radiographs showing external fixation in situ . \n figure 4:external fixation used to facilitate tibiocalcaneal arthrodesis post talectomy .\neight months since the initial presentation , the patient was taken to the theatre where a large defect in the anterior dorsum of the foot , and the external fixator was adjusted in the foot to allow for exploration and debridement .\nthe abductor hallucis was identified and the tendon divided distally and mobilized and rotated to fill in the soft tissue medial defect .\ncalcium sulphate with vancomycin and gentamycin was inserted into the bony defect , and external fixation frame was adjusted back to its original position .\nthe wound was closed using the abductor hallucis and skin graft from the right lateral leg .\npostoperatively the patient was put on intravenous teicoplanin and meropenem with oral stepdown to linezolid and ciprofloxacin . on discharge once the infection was controlled the patient s crp was 6.0 , white cell count 7.9 and neutrophils 4.0 .\nafter having the external fixation for 8 months in total , it was removed when fusion was deemed adequate on computed tomography imaging ( fig .\nshe was instructed to weight bear while in a plaster of paris cast for 14 days and then a moon boot for 14 days .\ntwo months after this , the patient was mobilizing without issues and was doing well . at 12 months\n, the patient stated that she is able to mobilize with any mild residual pain controlled with analgesia . \n\n( a ) anterior posterior view ; ( b ) lateral view . computed tomography scans illustrating tibiocalcaneal fusion 1 year postoperatively .\nmidfoot injuries with talar infections can often lead to below - knee amputation with the main goals of treatment being to successfully treat the infection and maintain a functional foot . in adults ,\nmost work focuses predominantly on internal fixation techniques or a combination of internal and external fixation .\nmost reports of arthrodesis following talectomy are for patients with charcot deformities rather than traumatic injuries with osteomyelitis . to successfully treat patients with infected midfoot injuries ,\ncalcium sulphate with antibiotics was used intraoperatively in the fusion site with some evidence supporting its use in deep foot infections . following this ,\na long course of intravenous antibiotics was used according to the sensitivities of the microorganisms growing in the region .\nexternal fixation facilitates soft tissue healing , allows earlier weight bearing , closer monitoring of surgical incision sites and postoperative adjustments .\nfabian and colleagues concluded that tibiocalcaneal fusion in seven charcot joint patients using external fixation alone was unlikely to lead to fusion but the fibrous healing was sufficient .\nagarwala s group and dennison s group report full fusion in all of their patients undergoing arthrodesis using external fixation [ 8 , 9 ] .\nour results are in concordance with work of agarwala and dennison et al . in that external fixation\nthere is a need for randomized controlled trials to investigate the most appropriate fixation technique for tibiocalcaneal arthrodesis . in conclusion , we report a good outcome treating an open 3c gustilo anderson fracture complicated by osteomyelitis , necrosis and inadequate soft tissue coverage .\nour management involved a single - staged talectomy to remove the infected bone and tackle the inadequate soft tissue coverage , external fixation for tibiocalcaneal arthrodesis to achieve joint stability and a combination of bone graft antibiotics and a course of intravenous and oral antibiotics postoperatively to deal with the underlying osteomyelitis .", "answer": "foot fractures vary in severity with complex midfoot fractures having poor morbidity rates and high amputation rates . \n complex midfoot fractures are rarely reported since they are uncommon and only treated in specialist centres . \n given the important role of the midfoot in foot function , reconstruction is preferable . \n soft tissue management on the dorsal aspect of the foot poses further challenges to reconstructive surgeons . \n we report a case of a 55-year - old woman who sustained an open 3c gustilo \n anderson fracture that was initially treated with open reduction internal fixation and free flap . \n she subsequently developed flap and internal fixation failure with osteomyelitis of the talus . \n we report a good outcome using primary limb shortening with a talectomy , tibiocalcaneal arthrodesis using external fixation and a combination of vancomycin - loaded calcium sulphate and intravenous antibiotics in our patient .", "id": 692} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\naneurysmal bone cysts ( abcs ) are rare entities which cause expansile and destructive bone lesions characterized by reactive proliferation of connective tissue1,5 ) .\nthey are benign lesions and can occur in any part of the skeleton and the spine can be affected up to 30% of the cases .\nabcs can cause symptoms such as back and/or dorsal pain , neurological deficitis , and pathological fractures .\nalthough abcs mostly occur in the distal part of femur and/or proximal part of the tibia , some cases have been reported in pelvis and posterior elements2,4,5 ) .\nabcs can occur rarely in the sacrum and this location has some difficulties in treatment because of the relations with the sacral nerves .\ntogetherness of abc and fibrous dysplasia , giant cell tumors and/or osteoblastomas are defined as secondary abc by some authors and this association was seen aproximately in 20 - 30% of cases .\ndiagnosis can be verified by ct scans and mri . in this paper , authors reported two rare cases with thoracic and sacral aneurysmal bone cysts .\na 14-year - old male admitted to neurosurgery department with suffering of being unable to walk for 15 days .\nthoracic mri images and ct scans demonstrated a mass which causes mass effect on spinal cord ( fig .\n2 day he was mobilised and his neurological examination was enough for walking with arm holder on postoperative 7 day .\non the 5 months control of the patient there were no suffering and no instable images on x - ray and mr images ( fig .\nan 8-year - old male pateint admitted to us with right hip and back pain . in his history , he had fallen down from 2 meters .\nspinal mri revealed abc on the right side of the 3 sacral vertebra with an enlargement of 2419mm(fig .\nthe second case is under control and no surgical treatment is suggested because of the patient 's age and observing no neurological deficits at the patient .\na 14-year - old male admitted to neurosurgery department with suffering of being unable to walk for 15 days .\nthoracic mri images and ct scans demonstrated a mass which causes mass effect on spinal cord ( fig .\n2 day he was mobilised and his neurological examination was enough for walking with arm holder on postoperative 7 day .\non the 5 months control of the patient there were no suffering and no instable images on x - ray and mr images ( fig .\nan 8-year - old male pateint admitted to us with right hip and back pain . in his history , he had fallen down from 2 meters .\nspinal mri revealed abc on the right side of the 3 sacral vertebra with an enlargement of 2419mm(fig .\nthe second case is under control and no surgical treatment is suggested because of the patient 's age and observing no neurological deficits at the patient .\nknown as a non - neoplastic expansile bone lesion , abc has a consistance of blood - filled spaces separated by connective tissue septa containing bone and osteoclastic giant cells .\ndiscussions about thoracic and sacral aneurysmal bone cysts are limited and only a few cases have been reported3,7 ) .\npapagelapoulos et al described 44 pelvis abcs and 12 of them were in the sacrum6 ) .\nit is well known that total extirpation of sabc is so difficult and surgical results in treatment of sabc are excellent .\nthese clinical findings include leg weakness and numbness , bowl or bladder dysfunctions . in our cases\nup to 60 - 70% of abc cases that occured in spine present with neurological deficits .\nthe clinical aspects are pain due to the destruction and neurological deficits due to the fractures and compression . in our case\nthe diagnostic problems are because of the expeditious growth of abc and its expansive destruction of bone .\nthe diagnosis becomes more complicated if there is an extra - osseous and soft - tissue tumour mass .\nit also helps to evaluate the fluidfluid level , which is characteristic for abc on mr images1 ) .\nour first case was evaluated as a pathological fracture , and the patient underwent urgent surgery because of the compression on spinal cannal .\nbut the second case was so typical for abc on the radiological examinations as if in the literature .\nthe primary option for treatment is surgery . enneking classified 3 surgical types : 1-intralesional ( curettage and bone grafting ) , 2-marginal ( en bloc ) resection , 3-wide resection ( segmental resection)3,4,5,6,7 ) .\nthe most important factors in preoperative planning are the location and the growing pattern of the abc . if abc is growing superficially and besides if it is not involving the one - third of the bone , in this case it will be more advantageous .\nthis is really a good intervention for abc and local recurrences occur less com- monly . besides this\n, if the abc is so large and located in pelvis or spine extraperitoneal excision and bone grafting could be more difficult and risky .\nin similar cases like this , curettage and bone grafting remain a choiceable surgical technique .\nlow - dose radiotheraphy can be performed after curettage and bone grafting as an other option for treatment5 ) .\nage , location , size and number of mitotic figures have been suggested for recurrence treatment of abc is difficult and histological examination should be done to prevent overlooked of an underlying more aggressive neoplasm .", "answer": "aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue . \n they usually grow rapidly with hypervascularity . in clinical practice \n they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically . \n most cases have uncommon pain symptoms , but rarely , if fractures occur , neurological findings can be seen and the surgical treatment , if needed , could be difficult . \n we will discuss our evaluations to two cases that we experienced in our clinic in this report .", "id": 693} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nNi(II), Cu(II), and Zn(II) Diethyldithiocarbamate Complexes Show Various Activities Against the Proteasome in Breast Cancer Cells\n\nPaper sections:\n\nSince FDA approval of cisplatin 30 years ago, thousands of coordination compounds have been synthesized and screened. However, cisplatin and its analogues (carboplatin and oxali-platin), ranked among \"alkylating agents\", are the only metal-based anticancer drugs in common use.1 Because many metal-based compounds are effective in vitro,2 it is a great challenge to find an in vivo active metal drug sufficiently safe for clinical use. One of the promising strategies to accelerate drug discovery and development research seems to be in finding new uses for old drugs. Once approved, these drugs can quickly enter phase II clinical trials and save a lot of time and money.3-5
Along that line, it deserves attention that an old anti-alcoholic drug disulfiram (tetraethylthiuram disulfide), in combination with zinc gluconate, has been reported to reduce hepatic metastases and produce clinical remission in a patient with ocular melanoma.6 Furthermore, disulfiram mixed with copper was found to selectively destroy melanoma cells in vitro.7 The antimelanoma activity of disulfiram was suggested to be attributed to diethyldithiocarbamate (EtDTCa) complex with copper because disulfiram can be converted to EtDTC in the body.8 Also, few other metal-dithiocarbamate complexes were shown to be effective against many types of cancer cells in vitro and in vivo.9-13 However, the involved molecular mechanism has not been completely defined.
The proteasome inhibition is a new and viable strategy in cancer therapy with the first-in-class approved drug bortezomib (dipeptide boronic acid analogue) as a successfule example.14 A giant protease responsible for degradation of about 90% cellular proteins, the proteasome is usually targeted at its proteolytically active \u03b2-rings (Figure 1). However, there is an increasing demand for new approaches to inhibit the proteasome, e.g., by targeting its so-called 19S particle (Figure 1).15 This component of the proteasome is responsible for recognizing ubiquitinated target proteins and their further processing (cleavage of ubiquitin chain) before the degradation.16 The deubiq-uitinating activity of 19S particle is dependent on a metal-loisopeptidase with a coordinated zinc ion,17,18 and this structural motif in 19S particle (JAB1/MPN/Mov34 domain or JAMM domain) has been suggested as a perspective target for anticancer drugs.19
In our current work, we show that synthetic and well-characterized complexes of three metals (Cu, Zn, and Ni) with EtDTC have different abilities to inhibit purified 20S proteasome (without 19S particles containing JAMM domain) and cellular 26S proteasome (with JAMM domain-containing 19S particles).
Regarding the metals, we selected zinc and copper as their EtDTC complexes were reported to suppress cancer growth in vivo, while nickel was used to create stable complexes with a coordination sphere similar to that of Cu(II) and Zn(II).
These complexes were prepared as described previously,20 and their molecular structures were confirmed using X-ray single-crystal diffraction (for details, see Supporting Information).
In view of the fact that disulfiram was reported to be able to inhibit the proteasome activity in MDA-MB-231 breast cancer xenografts with elevated copper levels, we decided to test the complexes in this highly malignant and metastatic cell line (experimental procedures are summarized in Supporting Information).21 We determined: (a) toxicity of synthetic compounds, (b) cellular morphological changes after treatment, (c) activity of the proteasome in the treated cells, and finally, (d) ability of the three complexes to inhibit purified 20S proteasome.
We found that Ni(II) complex was quite inactive to MDA-MB-231 cells in all the experiments. In a sharp contrast, both Zn(EtDTC)2 (the putative active compound in disulfiram/zinc gluconate treatment of metastatic melanoma) and Cu(EtDTC)2 were toxic to these breast cancer cells, associated with inhibition of cellular 26S proteasome (Table 1). When a purified 20S proteasome was used, both Zn(EtDTC)2 and Cu(EtDTC)2 showed much less inhibitory activity than against cellular 26S proteasome (Table 1).
Our previous work with different ligands (including dithio-carbamates) and their metal complexes suggested that the proteasome-inhibitory effects were strictly attributed to the complexes with specific metals. Ligands alone were active only against the tumor cells grown in copper-enriched medium, which increased the level of cellular copper available for reacting with the ligand within the cells,22 or against the tumors in vivo (that have elevated copper levels as well).23
The stability of dithiocarbamate complexes with metals within the cells has not been directly proved yet, although some of these complexes, such as Cu(EtDTC)2, seem to be stable in brain tissue.24 However, the putative (in)activity of our currently reported compounds toward the proteasome could be explained by their molecular structures. Until now, almost nothing is known about interactions between metal complexes and JAMM domain (except for, e.g., JAMM domain protein inhibition by zinc acetate25). In recent years, we have published a number of metal complexes that inhibit the proteasome, specifically its chymotrypsin-like (CT-like) activity, and induce apoptosis in human cancer cells.10,13,22,23 On the basis of the published work on metal complexes, the proteasome and JAMM domain, we have recently suggested that dithiocarbamate complexes with metals could inhibit JAMM domain proteins.26 Here, in the light of new data generated with these three metal complexes against the purified and cellular proteasome, we are proposing that inhibition of JAMM domain in the 19S particle of the proteasome is responsible for the effect of the tested metal complexes observed in the breast cancer cells. Following arguments support our hypothesis.
The JAMM domain is very similar to the metal-binding domain of carboxypeptidase A because both of them comprise glutamine and two histidines, a water molecule and glutamine, or aspartate in nearly the same arrangement. Carboxypeptidase A was shown to be efficiently inhibited by Zn(OH)Cl, creating a binuclear complex with the zinc from the protein by displacing the water molecule27 (Figure 2).
To bridge the JAMM zinc by dative bond, the diethyldithio-carbamate ligand requires rich electronic density on the sulfur atom (Figure 2, the sulfur in pink). Recently, electronic densities on atoms and bonds within Ni(EtDTC)2, Cu(EtDTC)2, and Zn(EtDTC)2 were analyzed. The greatest \u03c3-repulsion (that moves electronic densities from the bond to the atoms) was found between Zn and S, while the lowest \u03c3-repulsion was found between Ni and S.28 Therefore, a sulfur atom within a zinc complex has higher electronic density compared to the sulfur atoms in copper and nickel complexes. Moreover, Zn(EtDTC)2 and Cu(EtDTC)2 are, in solid phase, actually dimers (for figures, see Supporting Information) with sulfur atom bridging two metals; the bond length of the Zn-S(bridge) is shorter than that of the Cu-S(bridge) (2.391 vs 2.779 \u00c5), suggesting the larger electronic density on the sulfur atom within Zn(EtDTC)2 compared to the one within the Cu(EtDTC)2 complex. Nickel complex, however, is not able to create dimers (according to our data).
From this point of view, Zn(EtDTC)2 should be most active against the JAMM domain of the 26S proteasome, Cu(EtDTC)2 activity would be less potent against the JAMM domain, and nickel complex would not be active at all. However, this needs to be confirmed by showing direct interactions between the JAMM domain and diethyldithiocarbamate complexes and consequent inhibition of JAMM activity.
We have also recently reported29 that another group of dithio-carbamate complexes with copper and zinc, Cu(PyDTC)2 and Zn(PyDTC)2 (Py = pyrrolidinedithiocarbamate), could inhibit CT-like activity of cellular 26S but not purified 20S proteasome. It is possible that the overall effect of metal-dithiocarbamates within the cell is a result of their different effects on CT-like activity located on 20S catalytic core and deubiquitinating activity located on the 19S particle (e.g., JAMM domain) within the 26S proteasome. Further electronic density analysis of different dithiocarbamate complexes would help in answering this question.
Moreover, the hypothesis that metal complexes might inhibit JAMM domain could also, in some way, explain several previously observed effects of dithiocarbamate complexes, including blockage of ATF/CREB DNA binding6 and inhibition of H4 histone acetylation30 that requires ATF/CREB DNA binding.31 According to our hypothesis, JAMM domain acts as a deubiquitinase that coordinates histone acetylation and deu-biquitination32 and by targeting this deubiquitinase, dithiocar-bamate complexes would be able to regulate acetylation and biological activity of H4 and other players.
", "answer": "A series of three complexes with diethyldithiocarbamate ligand and three different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography, and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes, but not nickel complex, were found to be more active against cellular 26S proteasome than against purified 20S proteasome core particle. One of the possible explanations is inhibition of JAMM domain in the 19S proteasome lid.", "id": 694} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbiopsies from the ampulla of vater are usually essential to diagnose premalignant and malignant lesions in asymptomatic or symptomatic patients .\nacute pancreatitis is an extremely unusual complication following non - thermal biopsy of the ampulla without attempted cannulation .\nwe present this case because of its rarity and the accompanying intense clinical manifestations without further severe consequences .\na 51-year - old man underwent two gastroscopies over the prior 2 years with the indication of intermittent dyspepsia . on the last endoscopy ,\nthe ampulla of vater was described as bulging ; biopsies were performed and histological examinations revealed mild chronic , nonspecific , inflammatory mucosal lesions of the ampulla and duodenum , with regional architectural disturbances , epithelial hyperplasia , accompanying mild nuclear stratification , and atypia , not fulfilling the diagnostic criteria for epithelial dysplasia .\nthe patient was referred to our clinic with persistent , intermittent epigastric discomfort and pain , and we therefore scheduled a repeat examination in order to exclude an ampullary tumor .\nthe extensive work - up after this episode did not reveal any aggravating factors for the embolism . in view of the results of the endoscopy\n, we advised the patient to discontinue acenocoumarol and changed to low molecular weight heparin ( enoxaparin 40 mg / day ) .\nthe patient was heterozygous for sickle cell disease ( hemoglobin electrophoresis : hbs , 29.5% ; hbf , 0.6% ; hba2 , 3.6% ) .\na side - viewing scope ( olympus tjf-145 video duodenoscope ; olympus , tokyo , japan ) was used with the patient under conscious sedation ( midazolam 2 mg , propofol 60 mg ) .\neight biopsies were obtained from the area around the ampulla with a reusable oval - cup forceps ( olympus fb-26n-1 ; olympus ) . no excessive bleeding\none hour after the meal , the patient experienced an acute , severe ( eight out of 10 ) , persistent abdominal pain with recurrent , unrelieved vomiting .\nhe contacted his family doctor but refused hospital admission and was monitored on an outpatient basis . on the second day , the patient reported less vomiting , but the pain was still intense and he additionally became febrile to 38.5c .\nhe was advised to stop solid food intake and only take regular oral hydration . on day 3 , the symptoms improved with no vomiting , milder abdominal pain , and a temperature less than 37.8c .\nserum and urine amylase levels were 845 u / l ( normal < 100 ) and 8,500 u / l ( normal < 460 ) , respectively .\nkidney and liver tests showed normal results except for a slight elevation of the alanine aminotransferase level .\nblood triglyceride level was 110 mg / dl ( normal < 150 ) and the calcium level was 9.2 mg / dl ( normal 8.5 to 10.2 ) .\na second abdominal ultrasound was unremarkable , while contrast - enhanced abdominal computed tomography ( ct ) revealed mild enlargement of the pancreatic head and stranding of the surrounding retroperitoneal fat ( fig .\neight tissue samples , with an approximate diameter of 1 to 3 mm each , were analyzed .\nhistological examinations revealed mild inflammatory mucosal lesions of the ampulla and duodenum , with regional gastric metaplasia , regional epithelial hyperplasia , and mild nuclear stratification , which did not meet the diagnostic criteria for epithelial dysplasia .\nthe majority of periampullary neoplasms are malignant , whereas benign neoplasms account for less than 10% of the cases . among benign lesions , adenomas are the most common , with a potential for malignant transformation .\nalthough biopsies are essential in the diagnosis and follow - up of these lesions , the histological distinction between normal and pathological features of the ampullary mucosa is often difficult to make on endoscopically obtained samples .\nacute pancreatitis is a well - recognized complication of endoscopic retrograde cholangiopancreatography , but is extremely rare after biopsy of the ampulla of vater without a previous attempt at cannulation .\nhowever , an asymptomatic increase in amylase concentration has been reported in up to 30% of cases . in the case we present ,\nthe diagnosis of acute pancreatitis was based on symptomatology in combination with the increase in serum and urine amylase levels , as well as the ct findings . to our knowledge\n, there are only three reported cases associating acute pancreatitis with endoscopic biopsies from the ampulla of vater .\nthe first case was reported in a patient with gardner syndrome , who developed acute progressive periumbilical pain radiating laterally to the back 4 hours after endoscopy , with temperature increasing up to 39.2oc on the following day , high serum amylase levels , and a ct scan that showed pancreatic enlargement and diffuse stranding of the peripancreatic fat .\nanother case of severe acute pancreatitis was attributed to endoscopic biopsies of the minor papilla in a patient with pancreas divisum and liver metastases due to colon cancer .\nthe third was also a case of severe pancreatitis with formation of a large pancreatic walled - off necrosis that was managed with ultrasonography - guided drainage .\nin all the aforementioned cases , abdominal pain was the presenting symptom and occurred 4 hours after sampling of the papilla .\nthe clinical profile and course of our patient was similar to the case with gardner syndrome , with intense symptoms but still not a severe form of pancreatitis .\nour patient was indeed on heparin up to 24 hours before the procedure , which in combination with the biopsy process could have led to the development of a small hematoma .\npatients with sickle cell trait , especially african - americans , are more prone to manifest deep vein thrombosis and pulmonary embolism , although this remains a matter of debate .\nvaso - occlusive phenomena have been described in patients with sickle cell trait ( splenic infarction or sequestration , hyphema , etc . ) .\nthe occurrence of a thrombotic event would have led to ischemic pancreatitis , which is also a very rare condition and is usually associated with a major circulatory event such as hemorrhagic shock .\nmucosal edema due to biopsies is the most plausible mechanism for pancreatitis in our case .\nwe tried to direct the biopsies to the area around the orifice , but due to edema and bleeding after taking the first samples , it is sometimes very difficult to ensure that one or more biopsies are not directed towards the orifice .\nthis same mechanism is also proposed by ishida et al . and morales and hixson , who reported cases of acute pancreatitis following endoscopic biopsy of the ampulla .\nishida et al . additionally mentioned that the rise in the pancreatic duct pressure must have been low and of short duration , as no dilation of the pancreatic duct was observed . despite the clear chronological association between sampling of the ampulla and acute pancreatitis in our patient\nno use of nonsteroidal anti - inflammatory drugs , paracetamol , proton pump inhibitors , antibiotics , or other commonly used medications were reported .\npropofol has rarely been associated with pancreatitis if large doses are given in patients with coexistent hypertriglyceridemia .\nwhen we reviewed both the patient s older and recent blood tests , no evidence of pathological values for lipids and/or calcium was found . to our knowledge\n, there is no association of flumazenil with pancreatitis , whereas midazolam - induced pancreatitis reports has been scarcely reported and is not well - documented .\nfinally , it is worth mentioning that our patient recalled having substantial epigastric discomfort that lasted for 24 hours after a previous upper endoscopy when biopsies from the ampulla had been taken .\none can assume that mild forms of pancreatitis may occur more often than is actually reported in the literature . in conclusion , we present a case of acute pancreatitis following biopsy of the ampulla .\nthe case is significant for certain characteristics that have not been described in similar cases .\nour patient s symptomatology was severe and not in parallel with the trivial laboratory and radiological pathology , and most importantly , with the excellent outcome .\nthe patient s medical history entails features of unknown importance for the pathogenesis of pancreatitis ( sickle - cell trait , previous use of anticoagulants , and repeat sampling ) , but these features may have contributed to the advent of pancreatitis ; therefore , this case may be worth reporting for future reference . finally , although pancreatitis after sampling of the ampulla is a rare complication , endoscopists should take it into consideration before the procedure and inform patients accordingly .", "answer": "a 51-year - old man underwent diagnostic work - up for an abnormal - appearing ampulla of vater . \n three hours after biopsy of the ampulla , the patient presented with intense symptoms suggesting acute pancreatitis , which was later confirmed with laboratory and radiographic examinations . \n other causes were excluded and the acute pancreatitis was considered a procedural complication . \n this is a rarely reported complication that must be taken into consideration when biopsies are performed in the ampulla of vater .", "id": 695} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfor instance , in 1999 , john chapin s laboratory at hahnemann university in philadelphia and my own laboratory at duke university collaborated in the first experimental demonstrations of a brain - machine interface in animals . in these experiments\n, rats learned to use the combined electrical activity of a handful of cortical neurons to move a robotic arm in order to obtain a water reward . around the same time ,\nniels birbaumer at the university of tbingen in germany reported how completely paralyzed patients learned to use brain - derived signals ( recorded though a classic method known as electroencephalography , or eeg ) to write messages on a computer screen . even in its initial version ,\nthis brain - computer interface was the only way for these locked - in patients to communicate with the external world .\nit was an early indication of bmis significant potential as new rehabilitation tools . in subsequent years\n, further animal experiments with bmis indicated that monkeys could learn to employ the combined electrical activity of hundreds of their cortical neurons to move multiple degree - of - freedom robotic arms , entire humanoid robots , and even avatar limbs and bodies without the need for any overt movement of their own bodies .\nsoon , initial clinical studies also reported that patients could rely on bmis to control the movements of computer cursors and robotic arms .\nas the bmi field rose to the forefront of modern neuroscience , the possibility of establishing a bidirectional dialogue between brains and artificial devices was also realized . in 2011 , through a technique called cortical electrical microstimulation , my laboratory was able to deliver simple tactile messages directly into the brains of monkeys .\nevery time one of our monkeys used its brain activity to move a virtual hand to scan the surface of a virtual sphere , a simple electrical wave , proportional to the virtual texture of the touched object , was immediately delivered to the animal s primary somatosensory cortex , an area known to be fundamental for the definition of one s tactile perceptions .\nafter a few weeks of training , by taking advantage of this direct and continuous inflow of tactile information into their brains , a pair of monkeys became capable of discriminating the fine texture of the virtual objects by using their virtual hands , as if they were using their own biological fingertips .\nwe called this new paradigm a brain - machine - brain interface ( bmbi , figure 1 ) .\nin 2009 , as a direct result of this auspicious first decade of bmi research , the duke university center for neuroengineering and the edmond and lily safra international institute of neuroscience of natal ( els - iinn , in brazil ) jointly created a nonprofit research consortium called the walk again project . by the end of 2012 , the walk again project received a grant from the brazilian government to assemble a large international research team of roboticists , neuroscientists , engineers , and computer scientists .\nthis international team joined with a brazilian multidisciplinary rehabilitation team , composed of physicians , psychologists , and physical therapists , to take on a very ambitious project : designing and implementing the first bipedal robotic exoskeleton whose movements could be controlled directly by human - brain activity .\nthe central goal of the first phase of project was to allow paraplegic patients suffering from severe spinal - cord lesions to use their eeg activity to control the exoskeleton s leg movements ( figure 2 ) and , in so doing , regain lower - limb mobility .\nin addition to restoring basic locomotion behaviors , the exoskeleton would be the first in its class to provide continuous sensory feedback to the user in the form of artificial tactile and proprioceptive signals . in december 2013 , a group of eight patients suffering from complete and incomplete spinal - cord lesions started the training process required for achieving proficiency in controlling a brain - controlled robotic exoskeleton .\nfour months later , all eight were capable of commanding the exoskeleton with their brain activity alone , and all had regained the sensation of walking in a laboratory setting .\nthe feeling of walking again was even more realistic in these patients because of the addition of two innovative technologies in the design of our exoskeleton .\nthe first was a new type of artificial tactile sensor known as artificial skin , developed by gordon cheng at the technical university munich .\nthese sensors were distributed across key locations of the exo s legs and feet to detect the device s movements and contact with the ground .\nthe second was an ingenious haptic display , created by hannes bleuler s laboratory at the cole polytechnique fdrale de lausanne ( epfl ) in switzerland , that allowed the tactile feedback signals generated by the arrays of the artificial sensors to be delivered to the skin of a patient s forearms .\nfor the haptic display to work properly , patients had to wear a special shirt containing a linear array of small vibromechanical elements in the distal half of each sleeve while walking with the brain - controlled exoskeleton .\nto celebrate a major first step toward the development of a new generation of neuroprosthetic devices , one of our patients , juliano pinto , who is paralyzed from the mid - chest down , was invited to help our team demonstrate our exoskeleton s enormous potential before the opening match of the 2014 fifa world cup in brazil on june 12 .\nfor the first time in history , a human subject showed that a brain - controlled exoskeleton could be used to initiate the kicking of a soccer ball .\nthe demonstration was witnessed by 70,000 fans at the itaquero stadium and an estimated 1 billion people watching on tv .\nseconds after executing this historic kick , juliano reported to us that he clearly felt his leg moving in the air during the moment at which the exo s foot made contact with the surface of the ball . according to juliano s perception , it was his own body , not the exo , that executed the kick .\nthe effort and complexity required to pull off that world cup demonstration well exemplifies the current state of the art of bmis . over the last 15 years ,\nand although the case has been made that bmis offer concrete hope for the future development of a variety of new neurorehabilitation tools , we are still a few years away from being able to produce neuroprosthetic devices that patients can routinely use outside well - controlled laboratory conditions . certainly ,\nat this point , we are very far from the braincaps imagined by science - fiction writers like clarke .\ndespite the uncertainty , recent experiments combining bmis with cortical electrical microstimulation effectively open the doors for more daring adventures .\nindeed , i could almost bet that clarke himself would have enjoyed the opportunity to be present when miguel pais - vieira , a portuguese postdoctoral fellow in my lab , demonstrated the operation of the first brain - to - brain interface designed to link two animals brains directly ( figure 3 ) .\nfirst proposed in my 2011 book beyond boundaries : the new neuroscience of connecting brains with machines and how it will change our lives , our brain - to - brain interface ( btbi ) paradigm , reported in 2013 , allowed a pair of rats to transmit and receive rudimentary mental sensorimotor messages . in one of the published experiments , the first rat of the pair , known as the encoder ,\nwas trained to use its facial whiskers to determine the diameter of a computer - controlled aperture placed inside a behavioral box . from trial to trial , the aperture could assume two distinct diameters , classified as narrow ( x mm ) or wide ( y mm ) .\nthe encoder s job was to use its facial whiskers to correctly judge the aperture s diameter and then indicate its value by placing its snout in one of two holes located in a nearby chamber .\nif the encoder nose - poked in the hole corresponding to the correct aperture diameter , it received a water reward .\nas the encoder used its facial hair to evaluate the opening s diameter , electrical activity recorded from neurons located in its somatosensory cortex was combined and transmitted , via cortical electrical microstimulation , to the brain of a second rat , the decoder , located in a different behavioral box .\nthe decoder had no access to an aperture , so its facial whiskers were useless in solving the task and getting water . yet to receive such a reward , the decoder also had to indicate , by nose poking , the diameter of the aperture touched by the encoder . to do that , the decoder had to rely solely on the simple neural message being transmitted to its brain by electrical microstimulation .\nafter a bit of training , decoder rats became capable of using our brain - to - brain interface to successfully perform this task way above chance level .\nthis indicated that the brain of a decoder rat could make sense of the messages broadcasted by its associated encoder rat .\ninterestingly , since the encoder received an extra reward allotment every time a decoder was able to correctly indicate the aperture s diameter , encoder rats adapted their behavior and cortical activity to make it easier for their counterpart to complete the task , particularly after the latter committed a series of trial errors .\nthat further suggested to us that these rat dyads had established a new form of communication , despite the fact that neither animal was aware of its counterpart s existence . as an extra proof of the effectiveness of this btbi\n, we repeated these tactile - discrimination experiments by using an encoder rat placed in a laboratory in the els - iinn , in natal , brazil , while the decoder rat performed its trick in my lab at duke university , in the u.s . despite the distance and\nthe use of an average internet connection , the brain - to - brain interface worked as well as it did when the two animals were in the same laboratory . in a final test of our btbi , decoder rats used neuronal signals provided by the motor cortex of encoder rats to choose which of two levers to press , without ever seeing the visual cues that instructed the encoders to make the same decision in the first place .\nin other words , the brain - to - brain connection between the encoder and decoder rats allowed the latter to correctly make a motor decision based on visual cues experienced only by its encoder partner . during the past year , two other laboratories published studies involving brain - to - brain architectures .\nmoreover , a press release from a group at the university of washington indicated that the group had established a functional link between human subjects brains by combining two noninvasive techniques : eeg to record brain activity in the first subject ( encoder ) and transcranial magnetic stimulation ( tms ) to deliver an eeg - triggered signal to the second subject s ( decoder s ) brain . since the group has not yet published a full scientific report , it is difficult to evaluate what was really achieved .\nif anything , the limited description ( and video clip ) provided in the press release did not fully support the claim that a true functional communication between human brains occurred .\nthis is because , essentially , the encoder s eeg activity was simply used to trigger a magnetic stimulus in the decoder s motor cortex .\nas expected , every time this magnetic stimulation was delivered , the decoder subject produced an involuntary body movement . yet\nas such , i do not see how two brains shared a true message in this paradigm . on the other hand ,\nthe potential methodology for doing so was unveiled , and that was certainly enough to cause a significant media and public response .\nwe are currently investigating what kinds of social behaviors and global patterns of neuronal activity emerge when groups of animal brains are allowed to collaborate directly , through the employment of different types of brain - to - brain interfaces .\nthe central task of each of these animal brainets is to optimize the combination of neuronal activity , sampled from multiple brains simultaneously , into a supranervous system that is responsible for attaining a common behavioral goal , such as identifying a complex tactile pattern or moving an elaborate virtual limb .\nthe results of these studies , which are currently under review for publication , mostly focus on how btbis can enhance social interactions between animals and whether brainets could operate as a new type of computational architecture , like some sort of non - turing biological computer .\nin addition , these experimental paradigms allow one to study whether , in a still - distant future , artificial interfaces like these may be used to functionally reconnect brain areas where communication may have been disrupted by brain damage , such as that produced by strokes or other neurological disorders . right now\nhowever , seeking such a path has become a hallmark of our laboratory during the past decade . during this period ,\nwe have successfully translated similarly abstract basic - science ideas into potential new therapies for untreatable epilepsy , parkinson s disease , and disabling paralysis .\nall of these therapies are currently undergoing clinical testing worldwide . as exciting as these animal research projects are , none of them come close to competing with the fictional wonders of clarke s braincaps .\n, nobody would ever consider it ethically or medically acceptable to implant nanotubes or other types of electrodes in healthy human subjects for the purpose of testing a btbi , as suggested by clarke .\nbut even if , years or decades from now , better noninvasive technology enables us to record large - scale brain activity in real - time , at the millisecond scale , and then another efficient , noninvasive method might be used to deliver brain - derived messages to another human brain , it is highly unlikely that such a btbi would lead to the emergence of a fluid and efficient form of human communication , as long as we rely on digital computers to mediate this task . nor\ndo i believe that there will be a day in which braincap - like technologies will allow us to upload vast and complex information packets like a new language or a large amount of scientific knowledge , as clarke describes in his book into our brains , or to download all our memories or personal experiences into some sort of digital storage media .\napart from tasks such as motor control for which bmis can become very useful , mimicking higher - order brain functions , such as knowledge acquisition , memory storage , performance of cognitive tasks , and even consciousness , may be beyond the reach of binary logic , the basis from which all digital computers operate , no matter how simple or elaborate .\nan interesting corollary of this view is that we need not worry about the forecast that , in the near future , a really smart digital computer / machine will supplant human nature or intelligence . in all likelihood\n, this day will never come because , in a more - than - convenient arrangement , our most intimate neural riddles seem to have been properly copyright - protected by the very evolutionary history that generated our brains , as well as the very complex emergent properties that make it tick .\nas such , neither evolution nor neurobiological complexity can be effectively simulated by digital computers and their limited logic . in the end\n, this may not be so bad . like commander poole , as much as i would love to take advantage of a brand - new braincap minus the nanotubes to learn a few new intellectual tricks in a hurry , from the perspective of someone living in the early 21st century ( not the 31st ) , it is very difficult to imagine that any of us at this juncture in our history would , in good faith , feel comfortable in surrendering our final frontier of individual privacy , knowing that there is a chance , no matter how insignificant it may be , that an uninvited snoop may , nevertheless , want to take a peek .", "answer": "editor s note : every memory that we have , act that we perform , and feeling that we experience creates brainstorms interactions of millions of cells that produce electrical signals . \n neuroscientists are now able to record those signals , extract the kind of motor commands that the brain is about to produce , and communicate the commands to machines that can understand them and facilitate movement in the human body . \n research in this area has the potential to help paraplegics and others suffering from spinal - cord injuries to control machines with their thoughts and to bolster their ability to get around .", "id": 696} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen patients present with acute occlusion of either the internal carotid artery ( ica ) or the proximal middle cerebral artery ( mca ) within the therapeutic time window for restoration of cerebral blood flow , rapid recanalization using intravenous / intra - arterial ( ia ) thrombolysis and ia mechanical embolectomy is the goal of acute stroke management.11 ) however , if the patient presents beyond the therapeutic time window , life - threatening brain swelling and herniation , known as malignant mca infarction , can manifest within one week after the onset of stroke symptoms , along with a further decrease of consciousness and pupillary dilatation , necessitating early application of a decompressive hemicraniectomy for achievement of a better clinical outcome.24 ) the present article reviews the pathophysiology , historical background in previous studies , operative timing , surgical technique and clinical outcomes of decompressive hemicraniectomy for malignant mca infarction involving the mca territory with or without anterior cerebral artery and posterior cerebral artery territories .\nacute occlusion of either the ica or the proximal mca and insufficient collateral blood flow result in cerebral infarction of the mca territory and associated severe brain edema .\ncytotoxic edema results from failure of sodium - potassium adenosine triphosphatase in brain cell membranes and is followed by vasogenic edema in association with disruption of the blood - brain barrier .\nthe space - occupying lesion inside the cranial vault increases the intracranial pressure , thereby reducing the cerebral perfusion pressure and cerebral blood flow .\nin particular , a space - occupying lesion in a unilateral hemisphere causes pressure gradients between the supratentorial and infratentorial compartments and between the bilateral supratentorial compartments .\nthe transtentorial uncal herniation and the resultant displacement of the subthalamic - upper brainstem structures will impair the consciousness of the patient .\nthus , the aim of decompressive surgery is external herniation of the swollen infarcted brain for relief of brainstem compression and to reduce intracranial pressure .\nthe original purpose of decompressive hemicraniectomy was to help patients survive in cases of acute large hemispheric infarction.25 ) various case reports , retrospective studies and trials have suggested that this surgical treatment lowers mortality without increasing the incidence of severely disabled survivors.8)13)15)23)27)29 ) three european randomized , controlled clinical trials were conducted between 2001 and 2007.10)12)32 ) however , the decimal ( decompressive craniectomy in malignant middle cerebral artery infarction ) trial in france and destiny ( decompressive surgery for the treatment of malignant infarction of the middle cerebral artery ) trial in germany were stopped due to slow recruitment of cases and significant difference in mortality between groups.12)32 ) notwithstanding , the hamlet ( hemicraniectomy after middle cerebral artery infarction with life - threatening edema trial ) study , conducted in the netherlands , was completed and published in 2009.10 ) thirty two patients were randomly assigned to undergo surgical decompression and another 32 patients received the best medical treatment over a five - year period . according to the results , the use of hemicraniectomy resulted in a reduction in the number of case fatalities and poor outcomes ( modified rankin scale score 5 ) for patients with large hemispheric infarction who were treated within 48 hours of stroke onset .\nthe clinical outcome for patients is considered to show improvement with early surgical decompression before or immediately after any neurological deterioration related to brain swelling.10)22)26)28)31)33)36 ) this clinical deterioration includes pupil asymmetry , an altered consciousness level and aggravated hemiplegia.6 ) patients commonly manifest such neurological deterioration within one week after the onset of stroke symptoms . in particular , one third of patients show deterioration within 24 hours , while another third show deterioration 24 - 48 hours after symptom onset.24 ) to date , many clinical and radiological data defining early predictors of malignant hemispheric infarction have been reported.6)7)9)14)16)18)20)30)34 ) malignant edema after acute infarction can be predicted based on the volume of the infarcted brain tissue , however , extension of the initial infarct territory , delayed spontaneous recanalization of the occluded vessel , hemorrhagic transformation of the infarcted brain and the fluid volume state of the patient can all make the prediction difficult .\nthus , the predictors lack a sufficient predictive value with regard to selection of candidates for a decompressive hemicraniectomy prior to neurological deterioration . in addition , in order to ensure timely decompressive surgery , all patients with acute large hemispheric infarction should be observed in an intensive care unit or stroke unit setting .\nthus , determination of strict cutoff criteria with a high specificity and positive predictive value for malignant infarction is needed.21 ) the predictive value of the infarct volume assessed by early ct scan after stroke onset has not been found to be satisfactory , as follows : ( 1 ) hypodensity covering > 50% of mca territory within five hours after symptom onset was predictive of a malignant course with a sensitivity of 61% and specificity of 94%;34 ) ( 2 ) hypodensity covering > 50% of mca territory within 12 hours was predictive with a sensitivity of 64% and specificity of 66%;17 ) ( 3 ) hypodensity covering > 50% and 67% of mca territory within 18 hours was predictive with a sensitivity of 58% and 45% , respectively and specificity of 94% and 100% , respectively.7 ) one useful predictor is the initial infarct volume assessed using diffusion - weighted magnetic resonance ( mr ) imaging > 145 cm within 14 hours after acute mca occlusion , which achieved a sensitivity of 100% and a specificity of 94% in the study by oppenheim et al.20 ) the cutoff criteria for lesion volume and associated midline brain shift for prediction of malignant edema should differ according to the timing after stroke onset.4)21 ) gerriets et al . reported a midline shift 2.5 , 3.5 , 4.0 and 5.0 mm in transcranial color - coded duplex sonography as a predictor of malignant edema after 16 , 24 , 32 and 40 hours , respectively , after stroke onset with a specificity of 100% and positive predictive value of 100%.4 ) meanwhile , assessment of the final infarct volume can be performed using perfusion ct or perfusion mr images on admission , however , such perfusion parameters are still not optimal.3)30 ) in the mr perfusion study reported by thomalla et al .\n, perfusion lesion volume > 162 ml on a time - to - peak ( ttp ) map with a ttp delay threshold of > 4 seconds was found to predict malignant infarction with a sensitivity of 83% and specificity of 75%.30 )\nconceptually , decompressive craniectomy procedures include both internal and external decompression . in the case of external decompression , the frontal , temporal and parietal bones overlying the infarcted hemisphere\nare removed , allowing for external herniation of the swollen infarcted brain . with the patient in a state of general anesthesia , a skin incision\nis started just above the zygomatic arch 0.5 cm anterior to the tragus and then carried superiorly and posteriorly over the ear and around the parietal bone to the contralateral frontal midpupillary line .\nthe hemicraniectomy then involves the removal of a large fronto - temporo - parietal bone flap , as large as possible .\nthe bone flap is made anteriorly in order to avoid violation of the frontal sinus , except in the case of a huge frontal sinus .\nthe medial limit is 2 cm from the midline , in order to minimize venous bleeding on the dura .\nthe posterior limit of the bone flap is approximately 5 - 6 cm posterior to the external auditory canal , thereby covering the mca territory posteriorly and allowing for a neutral head position without compressing the brain .\ninferiorly , the temporal squama is removed to the level of the zygomatic arch . following a stellate - shaped dural incision ,\nit is commonly recommended that the infarcted brain tissue not be removed due to the presence of a salvageable penumbra area or viable tissue.10)12)32 ) however , the internal decompression ( removal of the infracted brain tissue and/or an anterior temporal lobectomy ) can be performed for patients with whole hemispheric infarction.19 ) expansive duraplasty is then performed using a large flap of pericranial tissue or an artificial dura substitute .\nthe dimensions of the expansive duraplasty should be extended in order to accommodate the subsequent aggravation of the brain edema .\nmultiple dural tenting sutures , bipolar coagulation of bleeding points on the dural surface , application of commercial hemostatic materials and placement of a closed suction drain in the epidural / subgaleal space are all used .\nfinally , the temporalis muscle and skin flap are reapproximated and sutured layer by layer .\nhowever , the temporalis muscle and fascia can be resected in order to maximize external herniation of the swollen brain .\nremoval of the temporalis muscle does not cause problems with chewing , as the grinding phase of the closure stroke only requires one - third of the maximal bite force and only leads to a minimal decrease in the maximal bite force.1)5 ) resection of the temporalis muscle and fascia provides a two - fold volume expansion on average when compared with the conventional technique on postoperative day 3 ( fig .\n1).22 ) technical obstacles to obtaining the best external decompression are an insufficient craniectomy size , epidural / subgaleal hematoma , thick and swollen temporalis muscle , tough and inelastic temporalis fascia and tight scalp.2)22)35 ) making hemicraniectomy as large as possible , meticulous hemostasis and resection of the temporalis muscle and fascia will all maximize external herniation of the infarcted brain .\ncranioplasty is then performed using the autogenous bone flap two to three months after the craniectomy .\nafter decompressive surgery for malignant mca infarction , clinical outcomes at 6 - 12 months after stroke onset have been reported .\nfor the criteria determining favorable and unfavorable outcomes , a dichotomization of the mrs score between 0 - 3 and 4 to death or between 0 - 4 and 5 to death has been used ; however , an mrs score of 0 - 3 is most appropriate for a favorable outcome as it includes independent functional outcomes . in the hamlet study ,\nthe patients were randomly assigned to undergo surgical decompression or to receive the best medical treatment within four days of stroke onset.10 ) the decompressive - surgery group had a lower incidence of mortality ( 22% versus 59% ) and mrs 5 - 6 ( 41% versus 59% ) than the group that received the best medical treatment . however , the incidence of patients with mrs of 0 - 3 did not differ between the two groups ( 25% versus 25% ) .\nresults of a pooled analysis of the three european randomized controlled trials indicated a better clinical outcome than that of the hamlet study.31 ) performance of decompressive surgery within 48 hours of stroke onset resulted in reduced mortality and an increase in the number of patients who had a favorable functional outcome .\nin addition , more patients in the decompressive - surgery group had mrs 0 - 3 ( 43% versus 21% ) and mrs 0 - 4 ( 75% versus 24% ) compared with those in the control group who received the best medical treatment . in analysis of the three predefined subgroups of the decimal trial , in the decompressive - surgery group , younger age showed correlation with a favorable outcome and there was a trend toward a worse outcome in patients with higher infarct volumes.32 ) however , no significant difference in the clinical outcome with mrs scores was observed between surviving patients with dominant and non - dominant hemisphere infarction .\nin patients with malignant hemispheric infarction , decompressive surgery can reduce the number of cases of fatality and increase the number of favorable outcomes .\nin particular , if a decompressive hemicraniectomy is performed early , before irreversible cerebral herniation , using appropriate surgical techniques , favorable outcomes with functional independence can be achieved in a high proportion of patients .", "answer": "in spite of the best medical treatment , large hemispheric infarction , resulting from acute occlusion of either the internal carotid or the proximal middle cerebral artery with insufficient collateral blood flow is associated with a high case fatality rate of approximately 60% . \n thus , a decompressive hemicraniectomy is considered a life - saving procedure for this devastating disease . \n findings of three recent randomized , controlled clinical trials and their meta - analysis showed that early surgical decompression not only reduced the number of case fatalities but also increased the incidence of favorable outcomes . \n the authors review the pathophysiology , historical background in previous studies , operative timing , surgical technique and clinical outcomes of surgical decompression for malignant hemispheric infarction .", "id": 697} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto the surprise and deep disappointment of all involved in the treatment of lung cancer , several large trials did not demonstrate any benefit of tyrosine kinase inhibitors ( tkis ) as an addition to chemotherapy [ 13 ] .\nbasic and clinical research then focused on mutations of the gene for epidermal growth factor receptor ( egfr ) as a predictive factor for response to monotherapy with tkis and to development of new compounds with broader and/or irreversible inhibition . the biological basis for the negative experience with combined treatment\ngefitinib and erlotinib met all three standard criteria for inclusion in a combination with chemotherapy : activity as monotherapy , different mechanism of action , and different toxicity .\nwhy , then , did the combination not work ? as explained in a recent editorial\n, we believe that the cells of tumors sensitive to tkis are pushed into the g-0 phase of the cell cycle and therefore become resistant to cytotoxic drugs\n. if antagonism between the two classes of drugs is really the biological basis for the aforementioned negative experience , then an optimal combination of tkis and chemotherapy should be in an intermittent , rather than a continuous schedule .\nthis brief report presents a single - institution experience on intermittent chemotherapy and tki in a small series of patients with advanced adenocarcinoma of the lung .\nour hypothesis was that intermittent treatment would lead to superior time to progression , when compared to experience with chemotherapy alone .\nif confirmed , such a result would be a solid basis for a randomised clinical trial .\npatients eligible for the trial were chemonave with microscopically confirmed adenocarcinoma of the lung , had stage iii b ( wet ) or iv according to uicc - tnm classification ( 6th edition ) , had smoking history of less than 10 packs in years , had an ecog performance status 0 or 1 , and had adequate parameters of hematological , liver , and renal function to receive cisplatin - based chemotherapy . in the absence of neurological symptoms , patients with brain metastases were eligible and were treated with brain irradiation only in case of intracranial progression .\nall patients had their diagnosis confirmed by biopsy or cytology . at the time when the trial was initiated , testing for egfr mutations was not available . \nwithin three weeks prior to treatment , the precise extent of the disease was determined by chest x - ray and ct scanning of the chest , upper abdomen , and brain . since 2008 ,\npet - ct scanning has been available and included in the initial diagnostics and in followup .\nthe treatment started with four cycles of intermittent chemotherapy and erlotinib according to the following schedule : day 1 : gemcitabine 1250 mg / m in 30-minute infusion , day 2 : cisplatin 75 mg / m , with appropriate hydration and antiemetics , day 4 : gemcitabine 1250 mg / m in 30-minute infusion , days 515 : erlotinib 150 mg daily p.o .\nthe number of cycles depended on tolerance to cisplatin - based chemotherapy and was determined individually . immediately after the last cycle\n, patients continued with erlotinib 150 mg / m daily continuously until progression or unacceptable toxicity .\ndefinition of complete response ( cr ) , partial response ( pr ) , stable disease ( sd ) , and progression followed the recist criteria . \nthe first evaluation of response was done during the third cycle of intermittent therapy , with confirmation of response during the fifth cycle .\ncontrol radiological examinations were repeated every 2 months for chest x - ray , every 4 months for ct , and at 6 and 12 months for pet - ct ( only patients who had this examination during their initial diagnostics ) . in october 2010 , all biopsy samples were reviewed , and specimens with more than 10% of tumour tissue were analyzed .\ngenomic dna was extracted from formalin - fixed , paraffin - embedded tissue sections using qiaamp dna ffpe tissue kit ( qiagen , hilden , germany ) according to the manufacturer 's instructions .\nquantification of extracted dna was done on qubit fluorometer ( invitrogen , carlsbad , usa ) . to detect egfr gene - activating mutations , we used therascreen egfr29 mutation kit ( dxs diagnostics , qiagen , manchester , uk ) .\nall realtime pcr reactions were performed in a 25 l final volume on abi 7500 instrument ( applied biosystems , carlsbad , usa ) .\nafter standard chemotherapy for metastatic nonsmall cell carcinoma , the expected ttp is 5 months .\nthe size of this single - arm nonrandomised trial of intermittent therapy was based on the assumption of 9 months as the median time to progression ( ttp ) .\nto obtain such a result with a confidence interval of 612 months , we planned to recruit 40 patients .\nthe investigators strictly followed recommendations of the helsinki declaration ( 1964 , with later amendments ) and of the european council convention on protection of human rights in bio - medicine , as accepted in oviedo in 1997 .\nthe protocol was approved by the institutional review board ( institute of oncology , ljubljana ) and by the national committee for medical ethics , ministry of health , republic of slovenia .\none patient was later found to have metastatic carcinoma of the pancreas rather than primary lung cancer and was excluded from all further analyses . with 12 patients each ,\ntwelve patients were never - smokers , and most were in good general condition ( ps 0 - 1 for 21 patients ) . with the exception of a single patient with wet \nbone metastases were the most common site of metastatic disease , followed by pleura / pericardium , contralateral lung metastases , and liver .\ntwo or more sites of metastatic disease were documented in 4 and 12 patients , respectively ( table 1 ) .\nthree patients had only cytological diagnosis , and an additional 3 had biopsy samples too small to allow for analysis of egfr mutations in tumor cells .\nof the 18 adequate samples , 8 were positive for egfr gene - activating mutations .\nthe actual number of cycles of intermittent therapy was from 1 to 6 cycles ( median : 4 cycles ) . due to early progression ,\n7 patients were still on maintenance treatment with erlotinib , and an additional patient stopped treatment with erlotinib after 12 months in pet - ct confirmed complete remission ( figures 1 and 2 ) . for the remaining patients , median total duration of treatment was 10 months . during the initial phase ,\nside effects of maintenance with erlotinib were skin toxicity ( grade 3 : 1 pt ; grade 2 : 11 pts ) and diarrhea ( grade 2 in 1 pt ) .\nall patients are evaluable for response , and no patient has been lost to followup . for the whole group of 24 patients , complete remission ( cr ) was seen in 5 pts ; partial remission ( pr ) in 9 pts ( response rate 58% ) , minimal response or stable disease ( sd ) in 8 pts , and progression in 2 pts . a clear and statistically significant ( p <\n.05 ) correlation was seen between the presence of activating egfr mutations and response . among the 8 patients who were positive for egfr gene - activating mutations , 4 complete and\nno cr and only 2 pr were seen among the 10 patients negative for mutations ( table 2 ) . \nfor the whole group , median time to progression ( ttp ) was 13.4 months , and median overall survival ( os ) was 23 months .\nmedian ttp and os for this group was 21.5 months and 24.2 months , respectively .\nfor patients without egfr mutations , ttp was 5 months , and os was 7 months ( table 2 and figures 3 and 4 ) .\nthis clinical trial was launched at a time when routine testing for egfr gene - activating mutations was not yet available .\nselection of patients for a combination of chemotherapy and erlotinib was made on the basis of classical histopathology ( adenocarcinoma ) and smoking status . \nsince testing for egfr gene mutations is now available , it is clear that patients with activating mutations are those who really benefit from tkis . in addition ,\nstandard first - line treatment for patients with activating egfr mutations is now monotherapy with a tki [ 6 , 7 ] .\nsince continuing a trial with the same selection criteria and without considering the status of egfr gene activating mutations was not justified , the research group made a decision to close the trial and analyse the experience . in order to get a longer interval for intermittent erlotinib , gemcitabine was given on days 1 and 4 of the cycle . when compared to the standard day 1 and day 8 schedule\n, this minor modification in timing of cytotoxic drugs did not have any adverse effect on the tolerance to treatment .\nclearly , other platin - based schedules which apply chemotherapy on a 3-weekly basis ( such as pemetrexed - cisplatin or paclitaxel - carboplatin ) can offer an even longer interval for tkis and might be considered for future trials of intermittent treatment . \ntwo other groups recently reported promising experience with intermittent chemotherapy and tkis . in a trial from the usa ,\ntwo schedules of intermittent treatment were tested . in combination with pemetrexed ( 500 mg / m on day 1 ) , erlotinib\nwas given either as a pulse application in a high dose ( range : 800 to 1400 mg ) given on days 2 , 9 and 16 , or in lower doses ( 150250 mg daily ) on days 2 to 16 .\nwhile tolerance to this treatment was good , the small number and heterogeneity of patients recruited into this trial do not allow for any clear conclusion regarding the effectiveness of intermittent treatment . of more importance\nthis study from asia compared gemcitabine and either cisplatin or carboplatin to a schedule with addition of intermittent application of erlotinib ( 150 mg on days 14 to 28 of the cycle ) and reported significantly superior ttp with the intermittent schedule .\ntheir experience is most valuable but may not be of direct relevance for the rest of the world , due to the well - known differences in sensitivity of lung cancer to tkis between asian and caucasian patients . despite its small size ,\nour trial can offer valuable experience for further research on optimisation of treatment with combinations of chemotherapy and tkis .\nlooking at the whole series of patients , we can conclude that intermittent chemotherapy and erlotinib is a treatment of very low toxicity .\nit is also clear that the efficacy of treatment is closely related to the presence or absence of egfr gene - activating mutations . \nthe most important finding is the excellent response rate with a substantial proportion of complete responses and prolonged ttp and os for patients positive for egfr gene - activating mutations . for many years , the maximal expectation of a patient with metastatic nonsmall cell lung cancer was a partial remission of relatively short duration in the range of 5 to 9 months . with intermittent treatment ,\nwhile the number of patients in our trial is small and any definitive conclusion would be premature , we nevertheless believe that further research of intermittent therapy for patients positive for egfr gene - activating mutations is warranted . a randomised trial comparing first - line tki as monotherapy to the intermittent schedule should clarify the real value of this new approach .", "answer": "background . intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs . \n this hypothesis was tested in a phase ii clinical trial . \n patients and methods . \n eligible patients were nonsmokers or light smokers , chemo - nave , with metastatic adenocarcinoma of the lung . \n treatment : 4 to 6 cycles of gemcitabine 1250 mg / m2 on days 1 and 4 , cisplatin 75 mg / m2 on day 2 , and erlotnib 150 mg daily on days 515 , followed by erlotinib as maintenance . results . \n 24 patients entered the trial . \n four pts had grade 3 toxicity . \n complete remission ( cr ) and partial remission ( pr ) were seen in 5 pts and 9 pts , respectively ( response rate 58% ) . \n median time to progression ( ttp ) was 13.4 months and median overall survival ( os ) was 23 months . when compared to patients with negative or unknown status of egfr mutations , \n 8 patients with egfr gene activating mutations had significantly superior experience : 4 cr and 4 pr , with median ttp 21.5 months and os 24.2 months ( p < .05 ) . conclusions . \n intermittent schedule with gemcitabine , cisplatin and erlotinib has mild toxicity . for patients who are positive for egfr gene activating mutations \n , this treatment offers excellent response rate , time to progression and survival .", "id": 698} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhile over 90% of vulvar malignancies are squamous cell carcinomas , other histologic types include melanomas , basal cell carcinomas , sarcomas , extramammary paget 's disease , and bartholin gland adenocarcinomas .\n ectopic breast tissue in the vulva was first described by hartung in 1872 , and since that time , several cases of both benign and malignant lesions arising in vulvar mammary tissue have been reported ( van der putte , 1994 ) .\nthe histology of the mammary - like tissue has multiple forms , ranging from simple , wide , slightly coiled tubular glands with a smooth outline , to more complicated forms in which the coiled structure has numerous branches and acini forming lobules .\nsimilar to normal breast tissue , both epithelial and myoepithelial cells are present and the glands are subject to both the dysplastic and malignant changes that are seen in normal breast tissue ( van der putte , 1994 ) . we report a case of a mammary - like invasive carcinoma presenting as an asymptomatic vulvar nodule .\na 65 year old , multiparous , postmenopausal female status - post total hysterectomy with bilateral salpingo - oophorectomy 39 years prior for symptomatic myomatous uterus , presented for her annual well woman exam .\nshe was without complaints and review of systems was negative ; specifically , she denied any recent history of unintended weight loss or gain , fever , chills , nausea , melena or hematochezia , vaginal bleeding or discharge , abdominal pain or fullness .\nher last mammogram was 12 years prior , after which she was diagnosed with right breast ductal papilloma which was excised .\nin addition to her prior hysterectomy , gynecologic history was significant for estrogen replacement therapy for 20 years , which she stopped after developing what she reported as\ntwo years prior to presentation , she had such a lesion removed from her right labia that had been present for one year and pathology was benign , per patient . on further discussion , she reported that the lesion had returned , was not painful , and was not associated with any further growth for the last six months .\nclinical breast examination did not demonstrate evidence of palpable masses , retraction , skin changes , or axillary adenopathy .\ngenital examination revealed a mobile , soft , non - tender , 2.5 0.75 cm nodule at 11 o'clock on her right labia majora .\nexcisional biopsy was performed in clinic , which revealed ductal carcinoma in situ with positive margins .\nthe patient then underwent a wide local excision of the area , which pathologically revealed invasive carcinoma with negative margins . the specimen from the wide local excision revealed a surface which was predominantly dark brown and wrinkled with a smooth , white\n, flat lesion measuring 0.8 0.3 cm ; the lesion was 1.2 cm from the 12 o'clock margin and 0.4 cm from the nearest ( 3 o'clock ) margin . on serial sectioning , the lesion was firm and white , and extended to a depth of 0.3 cm .\nmicroscopic examination revealed invasive carcinoma , at least 1.6 mm in greatest dimension ( fig . 1 ) , arising from within a background of mammary - like glands of the vulva demonstrating residual focal dcis .\nthe invasive lesion was noted to come within 1.3 mm of the margin , but all margins were negative for invasive disease .\nimmunohistochemical ( ihc ) stains including smooth - muscle heavy chain ( smm - hc ) , cd 10 , and p63 were performed and while there appeared to be some myoepithelial cells present along the smooth contoured edge by smm - hc only , there were other areas without any definitive basal cell / myoepithelial cell staining ( fig . 2 ) .\nthe area of concern demonstrated an irregular growth pattern ( no longer lobulocentric ) and was not associated with the prior biopsy site changes .\nthe tissue was then tested for hormone receptor status , and was found to be estrogen receptor ( er ) positive , but progesterone receptor ( pr ) and her2/cep17 negative .\nsecondary to narrow margins , re - excision was performed as well as an ipsilateral groin sentinel lymph node dissection , both of which were negative for dcis or malignancy .\nafter referral to a medical oncologist , she was also administered letrozole , an aromatase inhibitor , as adjuvant therapy for the er positive cancer .\na relative paucity of reports has documented complications of ectopic breast tissue in the vulva , beginning with hartung in 1872 .\nmammary ridges were theorized to have developed in a line from the axilla to the groin , and while the large majority of these ridges would normally regress , it was possible for rudimentary tissue to persist and develop into supernumerary mammary tissue ( van der putte , 1994 ) .\nthese mammary - like glands have an unknown function , but were distinguished from eccrine and apocrine glands .\nthe glands are simple tubular structures and are sparsely concentrated ; however , in some women they are more numerous and assume more complicated forms that resemble mammary tissue ( van der putte , 1994 ) .\nthe more complicated forms contain the basic coiled structure , but are obscured by numerous branches and acini which form lobules .\nthey are distinctly different from eccrine and apocrine glands by multiple factors including : 1 ) the type of epithelium , 2 ) the formation of diverticula , branches , and lobuli , 3 ) the shedding of clusters of epithelium , and 4 ) the expression of receptors for estrogen and progesterone .\nadditionally , mammary - like glands are also noted to be different than normal mammary tissue derived from the mammary ridges for multiple reasons as well : 1 ) their simpler configuration , 2 ) the higher number of glands than would be expected in rudimentary elements from mammary ridges , and 3 ) the direct relationship to eccrine glands .\nfurthermore , based on human embryologic studies , the mammary ridges could not involve the anogenital area , as at the height of the formation of the mammary ridges in 9 mm and 10 mm embryos , the labia majora are still far from their first appearance ( van der putte , 1994 ) .\nhowever , ectopic breast tissue has been described in the vulva , as well as in any other area of the body .\nboth ectopic breast tissue and mammary - like glands are susceptible to the physiologic , dysplastic , and malignant changes seen in normal breast parenchyma ( castro and deavers , 2001 ) , as there have been reported cases of invasive ductal carcinoma , ductal carcinoma in situ ( dcis ) , lobular carcinoma , mucinous adenocarcinoma , phyllodes tumors , and fibroadenomas in accessory breast tissue in the vulva ( lopes et al . , 2006 ) .\nalthough ectopic mammary tissue in the vulva is believed to be present in two to six percent of women , few cases of invasive ductal carcinoma have been reported in the literature ( kazakov et al . , 2011 ) .\nthe most common clinical presentation is a painless , solitary nodule , arising most often in the labia majora .\npatient age at presentation has been between 45 and 84 years , with most being 60 or older ( kazakov et al . ,\nmost carcinoma cases are histologically consistent with invasive ductal carcinoma , which is also the most common histology in orthotopic breast tissue ( kazakov et al . , 2011 ) .\nthis still leaves a differential diagnosis of primary mammary carcinoma , carcinoma of a skin appendage , or metastatic mammary carcinoma .\nrecognition of an in situ component is the best clue to establishing the primary origin in the skin , as was seen in our case , rather than a metastatic process ( kazakov et al . , 2011 ) .\nsecondary to the rarity of these lesions , there is no widely accepted recommended management strategy .\na recent review only identified approximately 25 cases reported in the literature ( benito et al . , 2013 ) .\nmanagement strategies have ranged from wide local excision for dcis to radical vulvectomy with bilateral inguinofemoral nodal dissection for invasive carcinomas ( irvin et al . , 1999 ) .\nadjuvant therapies have included radiation , anthracycline - based chemotherapy , and hormonal therapy , in an attempt to decrease recurrence and improve survival .\npatients that did not receive adjuvant therapy had a median survival of 4 months ( lopes et al . , 2006 )\n. only 1 patient out of 8 who received adjuvant therapy had died at the time of the previous publications , and the median survival was greater than 22 month ( lopes et al . , 2006 , irvin et al . , 1999 ) .\nnot surprisingly , there have been no clinical trials to evaluate the effectiveness of chemotherapy and radiation in such a small number of patients , so information on treatment has been , and should continue to be , extrapolated from treatment of cancers in the breast i.e. excisional procedure with or without lymph node dissection , followed by other adjuvant therapies as needed .\nthere is little to no data reporting on the utility of sentinel lymph node biopsy in this clinical scenario .\nbreast carcinoma is almost exclusively managed using sentinel lymph node mapping ( krag et al . , 2010 ) , while promising data support the use of this technique for vulvar cancer ( levenback et al . , 2012 ) .\nvulvar cancer is ideally suited for sentinel lymph node mapping secondary to the predictable lymphatic drainage of the vulva , the low false negative rate , and the substantially reduced morbidity ( e.g. lymphedema ) compared to a full groin lymph node dissection ( levenback et al . , 2012 ) .\nwe demonstrate this to be a potentially feasible technique for primary breast adenocarcinomas arising within the vulva in mammary - like glands , and in the context of such a rare histology , may be included in the management options of this disease .", "answer": "highlightsprimary invasive breast carcinoma can be found arising from within mammary - like glands in the vulva.there is no standard management strategy for this rare disease ; treatment recommendations should be similar to that for primary breast carcinoma.the use of sentinel lymph node biopsy may offer another management option for this disease .", "id": 699} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napproximately 1 - 5% of peripheral blood t cells express the t - cell receptor instead of the conventional t - cell receptor .\nthe versus t - cell lineage commitment during intrathymic t - cell development seems to be controlled by the signal strength provided to the t - cell receptor . in healthy donors ,\nmost blood t cells carry a specific t - cell receptor composed of v9 and v2 elements .\nin addition to effector functions shared with t cells , the v9v2 t cells can acquire professional antigen - presenting capacity characteristic of dendritic cells .\nin contrast to t cells , v9v2 t cells do not see processed antigenic peptides presented by major histocompatibility complex molecules , but rather recognize small phosphorylated non - peptide molecules ( phosphoantigens ) produced by many microorganisms but also by transformed eukaryotic cells . while microbial phosphoantigens are active at pico- to nanomolar concentrations , micromolar concentrations of the eukaryotic phosphoantigen isopentenyl pyrophosphate ( ipp ) are required for t - cell activation .\nsuch high concentrations are not achieved in the mevalonate pathway of isoprenoid synthesis used in non - transformed cells .\ninterestingly , human v9v2 t cells can kill a broad variety of epithelial tumor and leukemia / lymphoma cells .\nthe sensitivity of tumor cells to t - cell - mediated killing is increased upon treatment of tumor cells with aminobisphosphonates ( n - bps ) , drugs that are used in clinical practice for the treatment of osteoporosis and bone metastasis in cancer patients .\nn - bps inhibit the ipp - processing enzyme farnesyl diphosphate synthase ( fpps ) , thereby leading to an accumulation of ipp , which is then sensed by the t cells .\n t cells are poor producers of interleukin-2 ( il-2 ) , which is required for expansion of t cells .\ntherefore , attempts to activate tumor - reactive t cells endogenously by treating patients with n - bps must take into consideration an appropriate supply of il-2 .\nalternative strategies consider the adoptive transfer of in vitro expanded tumor - reactive t cells [ 10 - 14 ] .\nthe critical role of fpps in the control of intracellular ipp levels , and thus of the sensitivity of tumor cells toward t - cell killing , has been recently demonstrated using short hairpin rna - mediated knock - down of fpps .\nknock - down of fpps caused tumor cells , which otherwise were not recognized by t cells , to be susceptible to t - cell killing .\ntherefore , v9v2 t cells recognize and kill tumor cells on the basis of the unbalanced isoprenoid metabolic pathway in transformed cells , a pathway that is stable in non - malignant cells .\nthe discovery that n - bps activate t cells by inhibiting fpps , thereby leading to accumulation of ipp , has paved the way for proof - of - principle studies to activate t cells in patients with advanced cancer . in a phase i clinical trial , dieli and\ncolleagues treated patients with hormone - refractory prostate cancer with a standard application of the n - bp zoledronate ( 4 mg intravenous infusion every 21 days ) either with or without additional low - dose ( 6 10 iu ) subcutaneous application of il-2 .\nvarious parameters , including subset analysis of t cells , and serum levels of prostate - specific antigen and cytokines , were monitored over time . although the two cohorts comprised only a few patients , statistically significant effects of zoledronate plus il-2 on the mobilization and effector cell maturation of t cells were recorded . very importantly , the two cohorts showed distinct clinical outcomes , with clinical responses seen in six of nine patients treated with zoledronate plus il-2 but only in one of nine patients treated with zoledronate alone .\ninterestingly , a correlation between favorable outcome at 12 months and t - cell numbers or functional status ( or both ) was observed .\nsimilarly , wilhelm and colleagues had previously shown that the combined application of n - bp plus low - dose il-2 can induce objective tumor responses in patients with lymphoid malignancies .\ntogether , these studies support the view that application of n - bps plus il-2 is safe , induces in vivo activation / maturation of t cells , and may have beneficial effects in advanced cancer ( figure 1a ) .\n( a ) n - bps inhibit farnesyl diphosphate synthase ( fpps ) , thus preventing processing of isopentenyl pyrophosphate ( ipp ) to farnesyl diphosphate ( fpp ) .\nthe combined application of n - bp plus il-2 leads to in vivo activation of t cells .\n( b ) alternatively , t cells can be activated in vitro with n - bp or synthetic phosphoantigens in the presence of antigen - presenting cells ( apc ) and can be subsequently expanded to large cell numbers by an exogenous supply of il-2 for subsequent adoptive transfer into cancer patients .\nthe cell preparation can be performed under gmp ( good manufacturing practice ) conditions . in a case study reported by laggner et al . , regression of lung and bone metastases was observed in a patient with advanced stage melanoma upon systemic treatment with zoledronate and localized radiotherapy .\nalthough t - cell subsets were analyzed , it is difficult to ascertain a substantial role of t - cell activation in the resolution of metastases in this single case , particularly since il-2 was omitted in the treatment of this patient .\nin addition to their t - cell activating properties , n - bps also exhibit direct anti - tumor activities by both inhibiting proliferation and inducing apoptosis in tumor cells . while zoledronate seems to be the most potent t - cell - activating substance among the n - bps licensed for clinical application , derivatives of zoledronate with\nfurther improved t - cell - stimulating capacity and enhanced direct anti - tumor activity are under development .\nsuch modified n - bps might also exert improved in vivo activation of t cells when given to patients together with il-2 .\nt - cell - based immunotherapeutic strategy is the adoptive transfer of in vitro expanded v9v2 t cells from tumor patients ( figure 1b ) .\nrecently , efficient protocols for the large - scale in vitro expansion of v9v2 t cells based on stimulation with synthetic phosphoantigens or zoledronate have been established .\nfirst results indicate that the repetitive adoptive transfer of in vitro expanded t cells is well tolerated and may induce anti - tumor responses in patients with solid tumors , including renal cell carcinoma and myeloma .\nthe protocol developed by dieli et al . for the in vivo activation of t cells based on zoledronate plus\nlow - dose il-2 application is ready to be explored in larger clinical trials and in other tumor entities with poor prognosis , for example , pancreatic ductal adenocarcinoma where it might be combined with standard regimens such as gemcitabine .\nit is conceivable that this protocol can be further improved , for instance , by combination with tumor - targeting monoclonal antibodies . along this line\n, it has been shown that b - cell lymphoma or breast tumor cell killing by fc receptor - expressing t cells is enhanced in the presence of targeting antibodies rituximab ( cd20 ) or trastuzumab ( her2/neu ) , respectively . moreover , a t - cell - stimulating synthetic phosphoantigen was found to enhance the depletion of cd20 b cells by rituximab in a non - human primate model in vivo , pointing to the possible use of phosphoantigen plus anti - cd20 antibodies in the treatment of cd20 leukemias and lymphomas .\nfurthermore , cytokines promoting homeostatic proliferation and survival of t cells , such as il-15 , or cytokines potentiating the cytolytic activity and pro - inflammatory response , such as il-21 , might be combined with il-2 or used instead of il-2 .\nthis could be considered both for in vivo application together with n - bps and for optimization of in vitro expansion of t cells .\nin addition , future study protocols might include the combination of in vivo activation of t cells ( by n - bp or phosphoantigen plus il-2 ) followed by the adoptive transfer of in vitro expanded t cells , finally , it should be stressed that t - cell - based immunotherapy is not expected to replace established therapeutic protocols .\nrather , it might offer additional benefit to the patient , for instance , in combination with conventional chemotherapy .", "answer": "t lymphocytes are a numerically small subset of t cells with potent cytotoxic activity against a variety of tumor cells . \n human t cells expressing the v9v2 t cell antigen receptor recognize endogenous pyrophosphate molecules that are overproduced in transformed cells . moreover , the intracellular accumulation of such pyrophosphates is strongly enhanced by aminobisphosphonates used in the treatment of osteoporosis and bone metastasis in certain cancer patients . \n a new concept of cancer immunotherapy is based on the endogenous activation of t cells with aminobisphosphonates plus low - dose interleukin-2 .", "id": 700} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfive provinces in afghanistan were selected as a convenience sample ( accessibility ) that included both affected and unaffected areas .\ntwo accessible districts in each province were randomly selected by using a random number generator .\nrandom transects were used to select 10 households per village . to give an approximately equal male : female ratio , either the head of household , spouse ( woman ) , or the oldest person available at the time was selected .\nethical approval was provided by the institutional review board , ministry of public health , afghanistan . a standardized , structured questionnaire collected information on demographic and socioeconomic measures , avian influenza information sources and knowledge of appropriate preventive measures , poultry and animal handling , food and generic hygiene , and human influenza knowledge and treatment seeking .\nthe questions were ranked for importance in preventing avian influenza transmission in poultry or reducing human exposure and awarded 5 points , 3 points , or 1 point for correct answers . for each respondent ,\nthe sum of scores for correct answers divided by the sum of available points generated a percentage score .\ndata were double - entered by using microsoft access ( microsoft , redmond , wa , usa ) and analyzed by using stata 8 software ( stata corporation , college station , tx , usa ) .\npercentage scores for each respondent were ranked and classified as above or below the median .\nthe primary analysis was conducted to compare factors ( age , sex , socioeconomic status , provincial exposure to avian influenza iec campaigns , and poultry ownership ) associated with knowledge above the median . socioeconomic quintiles ( seqs ) were defined by principle components analysis using employment , education , and household assets as indicators ( 3 ) .\nfactors independently associated by univariate regression at the 95% confidence level were included in a stepwise multivariate logistic regression model . to numerically evaluate kap levels , a secondary analysis assessed differences between mean percentage scores , stratified by factors identified by logistic regression analysis .\ndata for 304 respondents were included in the analysis . of the 5 provinces , kabul and nangahar had had influenza outbreaks in poultry in 2007 .\nmedian age of respondents ( 38 years ) was high , but it reflected the age of heads of households and spouses .\npoultry ownership was reported by 65.2% of households ( > 95% backyard ownership ) and differed significantly between seqs ( poorest 53/62 [ 85.5% ] vs. least poor 20/55 [ 36.4% ] ; 30.0 , p<0.001 ) .\nprovinces exposed to avian influenza and intensive information , education , and communication campaigns ( kabul , march 2007 , and nangahar , february 2007 ) .\nseq was positively associated with kap score above the median ( lowest vs. highest : adjusted odds ratio [ aor ] 14.3 , 95% confidence interval [ ci ] 5.239.9 ) , as was provincial exposure to avian influenza iec campaigns ( aor 9.5 , 95% ci 4.918.6 ) .\nbackyard poultry ownership ( nonowners vs. owners : aor 0.3 , 95% ci 0.20.7 ) and older age group ( 1520 years vs. > 40 years : aor 0.3 , 95% ci 0.10.8 ) were both negatively associated . for secondary analysis ,\nmean kap score differed between seq ( p<0.001 , by analysis of variance ) and was higher in provinces previously exposed to iec campaigns ( 50.2% vs. 40.1% ; p<0.001 , by t test ) .\nreporting of sick or dead poultry to authorities was less frequent among lowest seq ( 8/47 [ 13% ] ) than highest seq ( 20/49 [ 37% ] ; 6.6 , p = 0.02 ) where selling poultry in the event of a local outbreak was more commonly reported ( 21/66 [ 66% ] vs. 10/51 [ 18% ] ; 27.2 , p<0.001 ) .\npresence of coops was less frequent in lowest seq ( 9/49 [ 18.4% ] ) than in highest seq ( 21/46 [ 45.6% ] ; 8.2 , p = 0.004 ) .\nhuman cases of avian influenza ( h5n1 ) have resulted from contact between humans and infected backyard poultry ( 4 ) .\nrisk to humans is also related to frequency of disease occurrence in the avian population ( 5 ) .\nrecently , human - to - human transmission has been reported in the neighboring northwest frontier province of pakistan ( 2 ) .\noverall knowledge was low , although in provinces exposed to intensive iec campaigns , kap scores of the population were higher .\nthe level of concern generated by the campaign , government response , media reports , and proximity to the outbreak are all likely to contribute to this association . despite this encouraging evidence , level of knowledge was far higher among persons with higher socioeconomic status .\nour results can be broadly generalized to the population , although we did not have access to unsafe districts ( most of the districts in southern and eastern afghanistan ) .\nthis limitation may introduce selection bias , which would underestimate the effect of socioeconomic status because those living in inaccessible areas likely have a lower status than persons in accessible areas .\npreintervention and postintervention surveys would provide a more robust measure of effectiveness . in the immediacy of an outbreak ,\nalthough there are limitations to the study design in concluding intervention effectiveness , the results provide evidence to support further intensive campaigns as a response to influenza outbreaks in poultry .\nseveral reports have examined kaps and behavior related to avian influenza ( h5n1 ) ( 69 ) .\nsimilar to the finding in the lao people s democratic republic ( 6 ) , our study suggests that conventional education and behavior change messages have a limited effect in populations with highest exposure .\nefforts to ensure that iec messages are suitable for lower socioeconomic groups should be adopted , specifically by improving the knowledge of community leaders , designing messages in a suitable format for the poor and illiterate , and ensuring that the most accessible channels are used .\nmessages should carefully balance the risk for human disease against potential nutritional and economic consequences of high population concern ( e.g. , food scares ) . successfully promoting behavior change is a lengthy process and requires frequent reinforcement .\nthe acuteness of avian influenza ( h5n1 ) outbreaks requires a concerted effort to enhance knowledge and change behavior among those most at risk in low - income countries .", "answer": "from february through april 2007 , avian influenza ( h5n1 ) was confirmed in poultry in 4 of 34 afghan provinces . a survey conducted in 2 affected and 3 unaffected provinces found that greater knowledge about reducing exposure \n was associated with higher socioeconomic status , residence in affected provinces , and not owning backyard poultry .", "id": 701} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 53-year - old caucasian female with complaints of dry eyes and a burning sensation in the eyes presented to our ophthalmology clinic 5 years ago .\nher medical history revealed that the symptoms had persisted for 10 years , with some relief with lubricating eye drops used every 0.51 h. prior serology studies for antinuclear antibodies ( ana ) , ro and la were all negative .\nshe denied any symptoms of dryness of her mouth , and she had no other comorbidities .\nclinical examination showed dry eyes , with slit lamp examination revealing thickening and hyperemia of the eyelids .\nshe was put on genteal gel alternating with artificial tears ( restasis eye drops ) four times / day . during the course of the next 5 years\n, she underwent multiple surgeries for persistent eye dryness , including three procedures of silicone punctual plug placement in each eyelid , permanent thermal punctual occlusion , and later , resection of the canaliculus due to repeat reopening of the punctum despite three permanent thermal occlusions and continued patient discomfort secondary to refractory dryness of the eyes . additional evaluation to determine the etiology of dry eyes was done .\nit revealed the presence of antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) , leading to the diagnosis of sjogren 's syndrome ( ss ) .\na 68-year - old caucasian female with a known history of rheumatoid arthritis ( ra ) presented to our ophthalmology clinic with complaints of persistent dry eyes and irritation for the last 25 years .\nshe had tried artificial tears , restasis eye drops and genteal gel with some relief .\nher prior workup by her rheumatologist included antibodies to ro and la , which were both negative .\non physical evaluation , she was noted to have dry eyes . slit lamp examination revealed hyperemia and thickening of the eyelids .\nher laboratory evaluation in our clinic included antibodies to ro and la that were negative and antibodies to ana and rheumatoid factor , which were both positive .\nevaluation of additional autoantibodies revealed the presence of antibodies to sp1 and psp , leading to the diagnosis of ss .\nantibody testing for sp1 and psp in both patients was done at immco diagnostic laboratory , buffalo , n.y .\na 53-year - old caucasian female with complaints of dry eyes and a burning sensation in the eyes presented to our ophthalmology clinic 5 years ago .\nher medical history revealed that the symptoms had persisted for 10 years , with some relief with lubricating eye drops used every 0.51 h. prior serology studies for antinuclear antibodies ( ana ) , ro and la were all negative .\nshe denied any symptoms of dryness of her mouth , and she had no other comorbidities .\nclinical examination showed dry eyes , with slit lamp examination revealing thickening and hyperemia of the eyelids .\nshe was put on genteal gel alternating with artificial tears ( restasis eye drops ) four times / day . during the course of the next 5 years\n, she underwent multiple surgeries for persistent eye dryness , including three procedures of silicone punctual plug placement in each eyelid , permanent thermal punctual occlusion , and later , resection of the canaliculus due to repeat reopening of the punctum despite three permanent thermal occlusions and continued patient discomfort secondary to refractory dryness of the eyes . additional evaluation to determine the etiology of dry eyes was done .\nit revealed the presence of antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) , leading to the diagnosis of sjogren 's syndrome ( ss ) .\na 68-year - old caucasian female with a known history of rheumatoid arthritis ( ra ) presented to our ophthalmology clinic with complaints of persistent dry eyes and irritation for the last 25 years .\nshe had tried artificial tears , restasis eye drops and genteal gel with some relief .\nher prior workup by her rheumatologist included antibodies to ro and la , which were both negative .\nher medications included methotrexate for her ra for the last 30 years . on physical evaluation ,\nher laboratory evaluation in our clinic included antibodies to ro and la that were negative and antibodies to ana and rheumatoid factor , which were both positive .\nevaluation of additional autoantibodies revealed the presence of antibodies to sp1 and psp , leading to the diagnosis of ss .\nantibody testing for sp1 and psp in both patients was done at immco diagnostic laboratory , buffalo , n.y .\nss is an autoimmune disease starting in the lacrimal and salivary glands but with eventual systemic involvement of multiple other organs .\nss can also occur secondary to other autoimmune diseases such as lupus and ra , known as secondary ss .\npatients with ss typically present with a dry , gritty sensation in the eyes and a dry mouth . at this stage\ntypically , involvement of the lachrymal and submandibular glands occurs before involvement of the parotid glands . due to this\n, the presentation of dry eyes may occur much earlier in the disease process and precede the presence of a dry mouth .\nabout 5% of the patients with ss develop b cell lymphoma , most commonly occurring in the salivary glands and gastrointestinal tract [ 1 , 2 , 3 ] .\nthe diagnostic criteria for ss include clinical criteria : a schirmer test with a result of < 5 mm of wetting/5 min or a rose bengal score of > 4 ( van bijsterveld ) as well as ocular and oral symptoms .\ndaily persistent dry eyes for more than 3 months , use of lubricants more than 3 times / day , a recurrent feeling of sand or gravel in the eyes as well as a dry mouth for more than 3 months with a glass of water required to eat dry foods further support a diagnosis of ss . in our clinics , the limit for schirmer 's test is set at 3 mm to reduce positive results in the normal population to < 15% .\nhistological criteria for ss include focal sialoadenitis , and serological criteria include ana , rf and antibodies to ro and/or la .\nthe diagnosis of ss is excluded if there is a history of head and neck radiation treatment , hepatitis c , aids , lymphoma , sarcoidosis , graft versus host disease or anticholinergic drugs .\nthe 2 patients described in this case report met the clinical criteria for ss based on dry eyes and a positive schirmer test but lacked antibodies to ro or la .\nthe autoantibodies that are most commonly believed to be associated with ss are ro and/or la antibodies .\nro ( ss - a ) is an extractable nuclear antigen that is composed of proteins 52 kd and 60 kd combined with cytoplasmic rna species [ 1 , 6 ] .\nantibodies to ro are found in patients with autoimmune mediated systemic connective disorders including ss .\nantibodies to ro are detected in 4060% of the patients [ 1 , 6 , 7 ] .\nla ( ss - b ) is a 48-kd protein and an extractable nuclear antigen .\nantibodies to la are detected in < 20% of the patients but they are highly specific to ss [ 6 , 7 ] .\nhowever , there are multiple other antibodies being studied , including antibodies to muscarinic receptor 3 , tissue kallikrein , alpha - fodrin , carbonic anhydrase ii and vi , psp and sp1 .\nthe significance of these autoantibodies has not been fully appreciated [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] .\none of the mouse models used to study ss is the interleukin 14 alpha transgenic ( il14tg ) mouse .\nit reproduces all events noted to occur in ss patients in the same relative time frame [ 16 , 17 , 18 ] .\nthe use of this animal model led to the discovery of the novel autoantibodies in ss .\nthese include antibodies to sp1 , carbonic anhydrase 6 ( ca6 ) and psp . the presence of these autoantibodies in the sera of patients with ss has been confirmed . as per these studies , only 25% of the il14tg mice developed ro and/or la antibodies .\ninterestingly , the time course in the development of the autoantibodies showed that the sp1 and ca6 antibodies were present very late in the disease .\nour first patient had symptoms of dry eyes requiring multiple procedures to help control them .\nour second patient had dry eyes for many years along with the comorbidity of ra .\nhowever , a diagnosis of ss was not made in either of our patients due to the lack of ro and/or la antibodies .\nthe detection of sp1 and psp antibodies in our patients led to the diagnosis of primary ss in the first and secondary ss in the second patient .\nthese cases stress the importance of using autoantibodies besides ro and la in the diagnosis of ss .\nfurther studies are in progress to define whether antibodies to sp1 and psp not only define early stages of ss but also particular forms of ss .\nmd , and l.s . , phd , participated in the discovery of the autoantibodies to sp1 and psp .\nthe suny at buffalo school of medicine holds a patent on these autoantibodies that is licensed to immco and nicox .", "answer": "purposethe purpose of this report is to describe 2 patients with persistent severe dry eyes , positive schirmer tests for sjogren 's syndrome ( ss ) but lacking antibodies to either ro or la . \n these patients were diagnosed to have ss by detecting antibodies to salivary gland protein 1 ( sp1 ) and parotid secretory protein ( psp ) . \n this report emphasizes the existence of patients with ss who lack antibodies to either ro or la and may therefore be misdiagnosed . \n detection of novel autoantibodies , including antibodies to sp1 and psp , are helpful in identifying these patients . \n initial presentation may simply be dry eyes.methodstwo patients who presented to our ophthalmology clinic are described . \n one of the patients underwent multiple procedures over a period of 10 years for severe xerophthalmia . \n the other patient had rheumatoid arthritis and xerophthalmia . \n however , in both patients , chronic xerophthalmia had been considered to be idiopathic because antibodies ro and la were negative . \n further serologic testing revealed antibodies to sp1 and psp.resultstwo patients who lacked antibodies to ro and la but not to sp1 and psp were diagnosed as having ss.conclusionpatients presenting with unexplained dry eyes may not always show the serology markers in the current criteria for ss , anti - ro and anti - la . in these cases , \n investigation for novel , early antibodies to sp1 and psp is of importance in the diagnosis of ss .", "id": 702} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal .\njepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .\nthe items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both\ntranslation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions .\ninternal consistency of each items of each of the four subscales of the translated jepqr - s was completed .\ninter - correlations between different subscales were also found . to find internal consistency of items under a subscale , item rest of test correlations were found .\nthe internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha .\nthe statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 .\na total of 226 bengali medium students ( male 99 and female 127 ) , studying in class seven and eight , were taken from two urban and two rural schools of west bengal .\njepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .\njepqr - s developed by corulla is 48 item self - reported questionnaire having four dimensions extraversion , neuroticism , psychoticism , and lie scale each of which has 12 items .\nthe items of the questionnaire were translated into bengali by two bilingual bengali personnel . where there were inconsistencies , both\nthe translators were consulted . also back translation of the questionnaire by an expert was made and where there were any inconsistencies , the translators were consulted to get best possible solutions .\ninternal consistency of each items of each of the four subscales of the translated jepqr - s was completed .\nto find internal consistency of items under a subscale , item rest of test correlations were found .\nthe internal consistency of the subscales of the translated questionnaire was found by calculating chronbach 's alpha .\nthe statistical analysis was made with the help of statistical package for the social science ( spss ) statistics 17.0 .\ntable 1 presents that the item rest of test correlations vary for the extraversion between 0.082 and 0.417 , for neuroticism between 0.127 and 0.552 , for psychoticism between 0.085 and 0.504 , and for the lie scale between 0.051 and 0.363 .\nitem rest of test correlations alpha reliability found for the four subscales were 0.620 for extraversion , 0.663 for neuroticism , 0.604 for psychoticism , and 0.620 for lie scale . the test \nretest reliabilities were found 0.659 for extraversion , 0.652 for neuroticism , 0.631 for psychoticism , and 0.621 for lie scale .\nthe present study was aimed to examine to what extent the bengali translation of the jepqr - s is functional in bengali cultured population . the results [ table 1 ] of the first stage of data analysis indicate that most of the items within a subscale have significant correlations with rest of the items .\nthe alpha coefficients of all the four subscales recorded in this study do not cross 0.7 , the level recommended by kline , but they are very close to it and satisfactory .\nalpha coefficients for extraversion , neuroticism and lie scale recorded in this study are less well relative to main stream studies , perhaps , due to cultural difference , as a measuring tool like personality test is always culturally loaded .\nsignificant observation of this study is that the alpha coefficient of 0.604 for psychoticism is impressive against the historic difficulties encountered by the subscale .\nretest reliabilities found in this study are satisfactory and the results are very similar to the findings of eysenck and eysenck which were for 13 years boys and girls with an interval of 6 months ; extraversion 0.67 and 0.76 , neuroticism 0.72 and 0.74 , psychoticism 0.63 and 0.66 , and lie scale 0.65 and 0.66 .\nresults relating to the main stream questionnaires provide that the dimensions of personality are not all orthogonal .\nthe inter correlations [ table 2 ] between the dimensions of the translated jepqr - s of the present study also show that they are not all orthogonal .\nneuroticism and lie scale also showed negative correlation significant at the 0.05 level . on the other hand , extraversion and lie scale also neuroticism and psychoticism both showed positive correlations significant at the 0.05 level .\nhowever , there is a significant negative correlation at the 0.01 level between psychoticism and lie scale while extraversion is independent of neuroticism .\non the basis of the present study , it may be concluded that the bengali version of the jepqr - s may be accepted as a functional tool for research work and educational purpose .\nit is further recommended to administer the bengali version of jepqr - s on a larger sample for determining the psychometric properties more accurately .", "answer": "background : personality measuring instrument plays an important role in many fields of human civilization and therefore , present study was aimed to find such an instrument for bengali speaking juniors.materials and methods : bengali translation of the short - form of the revised junior eysenck personality questionnaire developed by corulla was administered on a sample of 226 bengali speaking students ( 99 boys and 127 girls ) studying in class seven and eight taken from two urban and two rural schools \n . internal consistency of each item under a subscale was calculated ; internal consistency of each of the four subscales of the translated questionnaire was calculated ; test retest reliability was found with an interval of 3 months and inter - correlations between different subscales were found.conclusion:the findings provided satisfactory psychometric properties of the extraversion , neuroticism , psychoticism , and lie scale .", "id": 703} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nleri - weill 's dyschondrosteosis ( lwd ) is anautosomal dominant condition with variable penetrance characterized by mesomelic short stature and with madelung deformity .\nit is due to deletion or mutation in short stature homeobox ( shox ) gene . here\n, there is deficient growth of a volar and ulnar aspect of distal radialphysis , triangulation of corpus with proximal and volar shift of the lunate .\na 13-year - old girl referred to us with a history of deformity of bilateral forearm from the age of 5 to 6 years .\nthere was no history of pain in the joint of hands , trauma to the wrist and no history of similar illness in the family .\npatient was moderately built and significantly short for her age [ figure 1 ] . with height of 130 cm ( less than 3 percentile ) .\nupper segment was 69 cm , lower segment was 61 cm , weight of 35 kg and body mass index of 20.71 kg / m .\nsecondary sexual characteristic tanner - whitehouse staging - b4 ( breast ) , p4 ( pubic hair ) , a3 ( axillary hair ) her elder brother had normal height for age and no any hand deformities and so were her parents .\ninvestigation showed hemoglobin of 12.5 g / dl , liver function test and renal function test were normal ca= 9.0 mg / dl alkaline phosphates 260 iu and phosphorus = 3.5 mg / dl .\nx - ray bilateral wrist showed malformed medial radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity [ figure 2 ] .\nher ultrasound abdomen showed no hepatomegaly or splenomegaly and had normal sized uterus and ovary x - ray spine and x - ray elbow were normal [ figure 3 ] .\nher luteinizing hormone = 1.1 miu / ml follicle stimulating hormone = 2.4 miu / ml and karyotype was normal as was urine mucopolysaccharide screening .\nx - ray bilateral wrist based on the history , clinical examination , and investigations findings , the final diagnosis of lwd as a cause of madelung deformity was made .\nit is the most common cause of mesomelic deformity and is inherited as an autosomal dominant trait with variable penetrance .\nit is often seen in girls and becomes apparent in late childhood or early adolescence .\nmadelung deformity , beside is also found in turner 's syndrome , pseudohypoparathyroidism , mucopolysaccharidosis and achondroplasia of distal radial epiphysis .\nmadelung deformity was first described by malgaigne in 1885 and later by madelung in 1878 as a spontaneous forward subluxation of the hand .\nmadelung deformity is an ulnar and dorsal curvature of the distal radius due to deficient growth of the volar and ulnar aspect of distal radialphysis , increased inclination of the distal radial joint surface , triangulation of the corpus with proximal and volar migration of and a prominent dorsal subluxation of ulnar head .\nrecently , two subtypes of madelung deformity have been described , one with short stature and mesomelia consistent with lwd and the other with severe involvement of the entire radius with limited range of motion of extremity , markedly bowed appearance of the forearm and conspicuous radiographic deformity of the forearm and distal radius .\nthe pathogenesis of lwd is linked to deletion or mutation in shox gene , present in the pseudoautosomal region of the sex chromosomes - xp23 and yp11 .\nin early human embryos it is expressed in the developing limbs ( particular elbow , knee , distal radius / ulnar and wrist ) as well as first and second pharyngeal arches and plays an important role in bone growth as well as development .\nshox gene is also associated with short stature in turner 's syndrome and also some causes of growth retardation like lws and langers mesomelic dysplasia .\nmanagement is usually conservative . persistent pain and or severe deformity call for orthopedic surgery involving radial osteotomy .\nin addition , ulnar shortening in skeletally immature patient or excision of distal ulnar head in skeletally mature patients are done .\nsurgical prophylaxis by distal resection of the abnormal part of distal radial epiphysis and its replacement by autologous fat ( also known as physeolysis ) has recently been shown to restore growth and minimized deformity .\ngrowth hormone supplementation is found to increase final height in turner 's syndrome , lws but not in langers mesomelic dysplasia .\nhand deformity is corrected by orthopedic surgery and for shox gene related short stature food and drug administration has recently approved growth hormone therapy .", "answer": "madelung deformity is a rare inherited disorder associated with endocrine disorders like turner 's syndrome , pseudohypoparathyroidism , but can be seen with short stature homeobox deficiency conditions such as leri - weill dyschondrosteosis ( lwd ) and langers mesomelic dysplasia . \n it has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis ( mps ) and achondroplasia . \n madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna . \n a 13-year - old girl was referred to us for evaluation of bilateral deformity of wrist and short stature . \n there was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness . \n on x - ray , wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of madelung deformity . \n x - ray spine was normal . \n ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone . \n luteinizing hormone was normal and so was urine mps screening . based on the above points the diagnosis of lwd was made .", "id": 704} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey are congenital benign tumor accounting for 15 - 20 % of intraventricular mass but only about 1% of intracranial ones ( 1 - 3 ) .\nthey can be diagnosed at any age but usually become symptomatic in the third to sixth decades and more common in men than women .\nthey usually found incidentally and are asymptomatic ; but in some instances may associate with rapid neurologic deterioration , herniation , and sudden death .\nso , recognition of this rare but important diagnosis may result in decreasing mortality ( 4 ) . in this report\n, we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle .\na 13-year - old boy was brought to the emergency department ( ed ) with complaint of two times drop attack .\nthe patient mentioned that he felt sudden weakness in both lower limbs , which led to drop .\nthese attacks were happened about 4 hours before admission and he did not have any same experience previously .\nhe did not have complaint of nausea , vomiting , headache , vertigo , blurred vision , or palpitation .\nthe subject did not have any known structural or congenital heart disease , but suffered from asthma and used salbutamol spray irregularly .\nthe patient did not have trauma history and there was no positive history of any known medical illness in his parents or closed relatives . on arrival , he had 36.9c axillary temperature , 16/minute respiratory rate , 90/minute pulse rate , 120/80 mmhg blood pressure , and 96% oxygen saturation at room air . on physical examination , he did not have focal neurologic findings or even paresthesia or paraplegia .\ngeneral examination of head and neck , chest , abdomen , and limbs did not reveal any positive findings .\nfollowing the evaluation process , a brain computed tomography ( ct ) was performed ( figure-1 ) .\na hyperdense round lesion was seen in the third ventricle consequently caused that the corresponding physician requested a neurologic consultation in the ed . finally , the brain magnetic resonance imaging ( mri ) confirmed the diagnosis of third ventricle colloid cyst and the patient was underwent surgery and discharged without any problem ( figure 2 ) .\nthe colloid cysts commonly settle near the foramen of monro in the anterior third ventricle and so may encounter with drainage of the cerebrospinal fluid ( csf ) ( 3 ) .\nsince even a small lesion can block the mentioned foramen , these cysts may result in hydrocephalus and increase the intra cranial pressure ( 5 ) .\nincreased intracranial pressure can be manifested with headache described as severe and intermittent , with short duration , usually located frontally .\nin contrast with usual headaches , secondary to intracranial tumors , the colloid cyst induced headache can be relieved by lying down ( 4 ) .\nother symptoms include drop attacks , gait abnormalities , progressive dementia , and transient loss of consciousness . in children ,\nthe most common symptoms are nausea , vomiting , headache , diplopia , and papilledema ( 6 ) .\nthe classic clinical description of intermittent headaches and drop attacks occurs in only one - third of patients .\nsudden obstruction of the ventricular system and following rapid rising of intracranial pressure can lead to herniation and rarely sudden death ( 7 , 8) .\ncolloid cysts size varies from 3 - 40 millimeters in diameter , but the size do not related to their symptoms or outcome , as even small ones may lead to sudden death ( 9 ) .\ncolloid cyst is usually diagnosed by non - contrast computed tomography ( ct ) as an oval or rounded hyperdense mass on the anterior aspect of the third ventricle .\nthey may occasionally be hypodense or isodense to the brain , or found in other areas of the brain .\ncolloid cysts have different manifestation on mri . despite their variable signal characteristics , their location and shape help to the correct preoperative diagnosis in most patients ( 6 ) .\nhalf of the cases are hyperintense on t1-weighted mri images and hypointense on t2-weighted mri images respected to brain .\nisointense cysts are not easily identified on mri , and in such instances ct scan is more useful ( 9 , 10 ) .\nsmall asymptomatic colloid cyst can be considered for close follow up by serial examinations and neuroimaging ( 11 ) .\nthere is also the rare report of spontaneous resolving of the third ventricle colloid cyst ( 12 , 13 ) .\nall authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors .", "answer": "colloid cysts are mucous - filled masses with an outer fibrous layer . \n these cysts are rare developmental malformation and not a true neoplasm . \n they usually found incidentally and are asymptomatic ; but in some cases may associate with rapid neurologic deterioration , herniation , and sudden death . \n recognition of this rare but important diagnosis may result in decreasing mortality . in this report \n , we presented a 13-year - old boy with complaint of two times drop attack and final diagnosis of colloid cyst in the third brain ventricle .", "id": 705} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prevalence of kidney stones in the united states has risen steadily in recent years and correlates with population dietary changes .\nrelative dietary intake of fluid , sodium , calcium , oxalate , citrate , and animal - based proteins has a marked influence on stone risk .\naccordingly , an efficient assessment of a patient 's nutritional intake is important for the urologist and may enable an informed assessment and guided recommendations .\nthe traditional office based interview may not adequately assess the patient 's nutritional intake , due to time constraints and the detailed nature of a nutritional history .\nfurthermore , biases may exist both in how a patient wishes to represent themselves , and in how the practitioner presents a question .\nwe sought to determine if a physician 's impression of a patient 's dietary intake was dependent on the medium through which they obtained the nutritional data .\na typical office interview was compared to information obtained via a computerized clinical decision support system ( cdss ) , which presented a food frequency questionnaire ( ffq ) .\nfurthermore , the urologists made recommendations for dietary intervention based on the information ascertained via each method .\neach patient completed : ( 1 ) an office - based interview with one of two fellowship - trained endourologists , and ( 2 ) a ffq administered via a cdss , presented on an ipad .\neach urologist made two separate assessments via a likert - scale - based survey of the significance of a patient 's nutritional ( nutritional impact score ) and hydration factors ( hydration impact score ) as they pertained to stone disease ( fig .\neach assessment was followed by specific recommendations , such as reducing sodium intake , reducing animal protein intake , and increasing fluid intake .\nthe first assessment ( pre - ffq ) was made after the office - based interview with the patient but without reviewing the results of the ffq .\nthe second assessment ( post - ffq ) was made after reviewing the patient 's ffq results .\nif the urologist modified the nutritional impact score , hydration impact score , or treatment recommendations from the first assessment to the second , we assumed that the ffq results caused the urologist to believe that nutrition had a greater or lesser impact on the patient 's stone disease than previously assessed by the office - based interview .\nthe ffq used in this study is an 88-question nutritional survey that is similar to prior ffqs that have been validated by previous analyses for accurate assessment of a patient 's dietary habits . using the ffq , our patients recorded nutritional intake of those foods providing substantial quantities of the following : oxalate , animal - based protein , sodium , and calcium .\nintake of fruits and vegetables , fluids , and nutritional supplements was also assessed ( fig .\nquestionnaire results were entered in the ffq 's algorithm , which generated numerical scores corresponding to patient 's relative intake in each of the following domains : oxalate , calcium , sodium , purine , and fluids . for each patient , we compared pre - ffq nutritional impact score , hydration impact score , and treatment recommendations to respective post - ffq data points .\nour results were coded into the following binary variables , detailing the presence or absence of : increase in diet score , increase in hydration impact score , any change in treatment recommendations , addition of at least one treatment recommendation , and subtraction of at least one treatment recommendation .\na multivariate logistic regression model was fit to determine the impact of the numerical results of each domain in the ffq ( oxalate , calcium , sodium , purine , and fluids ) and the aforementioned binary variables .\neach patient completed : ( 1 ) an office - based interview with one of two fellowship - trained endourologists , and ( 2 ) a ffq administered via a cdss , presented on an ipad .\neach urologist made two separate assessments via a likert - scale - based survey of the significance of a patient 's nutritional ( nutritional impact score ) and hydration factors ( hydration impact score ) as they pertained to stone disease ( fig .\neach assessment was followed by specific recommendations , such as reducing sodium intake , reducing animal protein intake , and increasing fluid intake .\nthe first assessment ( pre - ffq ) was made after the office - based interview with the patient but without reviewing the results of the ffq .\nthe second assessment ( post - ffq ) was made after reviewing the patient 's ffq results .\nif the urologist modified the nutritional impact score , hydration impact score , or treatment recommendations from the first assessment to the second , we assumed that the ffq results caused the urologist to believe that nutrition had a greater or lesser impact on the patient 's stone disease than previously assessed by the office - based interview .\nthe ffq used in this study is an 88-question nutritional survey that is similar to prior ffqs that have been validated by previous analyses for accurate assessment of a patient 's dietary habits . using the ffq , our patients recorded nutritional intake of those foods providing substantial quantities of the following : oxalate , animal - based protein , sodium , and calcium .\nintake of fruits and vegetables , fluids , and nutritional supplements was also assessed ( fig .\nquestionnaire results were entered in the ffq 's algorithm , which generated numerical scores corresponding to patient 's relative intake in each of the following domains : oxalate , calcium , sodium , purine , and fluids .\nfor each patient , we compared pre - ffq nutritional impact score , hydration impact score , and treatment recommendations to respective post - ffq data points .\nour results were coded into the following binary variables , detailing the presence or absence of : increase in diet score , increase in hydration impact score , any change in treatment recommendations , addition of at least one treatment recommendation , and subtraction of at least one treatment recommendation .\na multivariate logistic regression model was fit to determine the impact of the numerical results of each domain in the ffq ( oxalate , calcium , sodium , purine , and fluids ) and the aforementioned binary variables .\nbetween the 2 urologists in the study , there was no significant difference in the average nutritional impact scores or average the hydration impact scores assigned . from pre - ffq\nto post - ffq , the urologist was more likely to increase the nutritional impact score if the patient had higher ffq scores for sodium ( odds ratio [ or ] , 1.02 ; p=0.02 ) or fluids ( or , 1.03 , p=0.04 ) . in other words\n, the physician interpreted a greater contribution of diet to the patient 's stone disease when the ffq indicated higher sodium or fluid intake ( table 2 ) .\nthere was no difference in hydration score rendered by the physician for patients who consumed increased oxalate , calcium , sodium , purine , or fluids ( table 3 ) .\na higher ffq score for oxalate was positively associated with the addition of at least one treatment recommendation ( or , 1.07 ; p=0.02 ) ( table 4 ) .\nstone disease is among the most common and costly urological conditions , with a lifetime prevalence of approximately 9% , and 5-year recurrence rates approaching 50% . in the united states alone ,\nthe economic burden of stone disease has been estimated to be over $ 2 billion annually .\nprevious studies have underscored the impact of diet on stone formation and the role of dietary interventions in prevention of stone disease .\nour study revealed that using a ffq to obtain the diet history impacted how urologists perceived the effects of diet and hydration on stone disease , as well as how urologists treated the stone disease .\ntherefore , it is important for the urologist to effectively and expeditiously obtain a thorough diet history .\ncertainly , the modern urologist experiences logistical and time constraints in his or her busy clinical practice . additionally , some patients may alter their responses to dietary questions in an attempt to represent their habits more favorably .\nfurthermore , even skilled endourologists and stone experts may not use the most effective questions to obtain the information necessary .\nfinally , a comprehensive stone clinic , complete with a dietician is favorable , but not feasible in every practice setting .\nprevious authors have found the ffq to be an effective tool for obtaining an accurate and objective diet history . as for the method of delivering the ffq\n, we believe that the computerized cdss provides physicians with a relatively bias - free mode of data collection as well as standardized evaluations of the data delivered in a timely fashion .\nin other medical applications , the cdss has been shown to improve practitioner performance and patient care , for instance , by reducing medication errors . in the present study\n, we found that the use of the ffq as a cdss can significantly alter the how the endourologist assesses the significance of dietary factors on a patient 's stone disease .\nmoreover , the recommended dietary interventions can change based on the results of the ffq . in our urolithiasis clinic ,\nnearly all of the patients ( 75 of 76 ) were willing to use the ffq .\nthese findings suggest that the addition of the ffq to the 24-hour urine collection and other components of the comprehensive stone evaluation may alter the assessment and plan for these patients .\nthe major limitation of our study is that we did not determine if use of the ffq leads to improved patient outcomes , such as decreased recurrence rates or increased patient satisfaction .\nfuture studies may be developed to link the use of the ffq to improved outcomes or patient encounters .\nwhile our study may not yet translate into improved patient outcomes , certainly others have shown that the use of cdss can improve efficiency .\nit is reasonable to hypothesize that improving efficiency may be a key component in improving patient outcomes .\nother studies have also shown that ffqs can play an integral role in assessing urolithiasis patients , especially in a multidisciplinary setting , where a patient 's diet may be a key focus in stone prevention .\nwhile our ffq was reasonably detailed , others have been able to streamline a more lengthy diet questionnaire into a more compact rapid food screener . in regards to assessing renal acid load in stone formers ,\nhis goal was to make this rapid assessment equivalent to a more lengthy diet questionnaire . in a follow - up study , patients were asked to complete both of these questionnaires , and their lake score assessment appeared as good as a lengthier questionnaire in determining renal acid load . while this particular study looked at a different aspect of stone disease , it appears that endourologists are attempting to gain detailed dietary information from their patients while continuing to improve efficiency and streamline their stone clinics .\ncertainly these approaches may prove worthwhile as we continue to develop this tool in our urolithiasis clinic .\nwe hope that our efforts may ultimately improve the efficiency and quality of care of our endourology patients .\ngiven the wide body of evidence supporting the use of dietary interventions in preventing stone recurrence , it is reasonable to hypothesize that recommendations made with potentially more complete and accurate data , obtained using the ffq , would confer improved outcomes .\nrandomized - controlled trials are necessary to evaluate the impact of utilizing the ffq as a cdss on stone patients to patient outcomes , such as recurrence rates , quality of life , and satisfaction with the clinical experience .\na self - reported , electronic version of the ffq may be helpful in the efficient assessment and counseling of patients with stone disease . with prior comprehensive knowledge of a patient 's nutritional intake ,\nthe urologist may be afforded more time with which to counsel patients regarding intervention and nutritional intake .", "answer": "purposeto evaluate a physician 's impression of a urinary stone patient 's dietary intake and whether it was dependent on the medium through which the nutritional data were obtained . \n furthermore , we sought to determine if using an electronic food frequency questionnaire ( ffq ) impacted dietary recommendations for these patients.materials and methodsseventy - six patients attended the stone clinic over a period of 6 weeks . \n seventy - five gave consent for enrollment in our study . \n patients completed an office - based interview with a fellowship - trained endourologist , and a ffq administered on an ipad . \n the ffq assessed intake of various dietary components related to stone development , such as oxalate and calcium . \n the urologists were blinded to the identity of patients ' ffq results . \n based on the office - based interview and the ffq results , the urologists provided separate assessments of the impact of nutrition and hydration on the patient 's stone disease ( nutrition impact score and hydration impact score , respectively ) and treatment recommendations . \n multivariate logistic regressions were used to compare pre - ffq data to post - ffq data.resultshigher ffq scores for sodium ( odds ratio [ or ] , 1.02 ; p=0.02 ) and fluids ( or , 1.03 , p=0.04 ) were associated with a higher nutritional impact score . none of the ffq parameters impacted hydration impact score . a higher ffq score for oxalate ( or , 1.07 ; p=0.02 ) was associated with the addition of at least one treatment recommendation.conclusionsinformation derived from a ffq can yield a significant impact on a physician 's assessment of stone risks and decision for management of stone disease .", "id": 706} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngck - mody ( gck diabetes , glucokinase diabetes , or mody2 ) is a monogenic condition caused by heterozygous mutations in the gene encoding glucokinase ( gck ) .\nit is characterized by chronic , lifelong , and mild hyperglycemia present from birth , and less than 50% of patients fulfil the criteria for overt diabetes .\nthe increased risk of atherosclerotic vascular disease as compared with healthy individuals without diabetes is known in subjects with impaired glucose tolerance , patients with type 2 diabetes , and patients with metabolic syndrome [ 3 , 4 ] .\nnoninvasive imaging techniques , such as carotid intima - media thickness ( cimt ) measurements , may help to stratify this risk of atherosclerosis , as well as the risk of myocardial ischemia : the cimt has been shown to independently predict coronary events in type 2 diabetes and cardiovascular diseases .\nhowever , the situation in gck - mody is likely to be different from that in type 2 diabetes : patients with gck - mody have increased fasting blood glucose and relatively low 2-hour post - ogtt blood glucose without other components of metabolic syndrome or insulin resistance .\nsuch a blood glucose profile has been shown to be associated with lower rates of cardiovascular mortality among patients with type 2 diabetes .\nimportantly , niskanen et al . demonstrated that components of insulin resistance syndrome , including hyperinsulinemia after an oral glucose load , serum lipid abnormalities , and elevated blood pressure , are major determinants of cimt in patients with diabetes . \nthe risk of macrovascular complications in gck - mody is considered low , but the data are scarce .\nwe aimed to evaluate the carotid intima - media thickness ( cimt ) as an indicator of this risk in gck - mody patients aging 35 years or older and their unaffected relatives , who share a similar environment and lifestyle .\nwe studied 27 patients from 20 czech families with genetically confirmed gck - mody ( age 3575 years ; median 46 years ) and 24 unaffected family members ( siblings , parents , and partners ) representing the control group ( age 3579 years ; median 50 years ) .\neach of the 20 participating families contributed 1 to 3 patients with gck - mody and 1 to 3 control individuals matched by age and gender .\ncontrol individuals with fasting blood glucose more than 5.6 mmol / l ( 100 mg / dl ) and/or with a known history of diabetes were excluded from the study .\nthe identification of families with gck - mody has been reported previously [ 9 , 10 ] .\nthe study protocol was approved by the ethics committee of the 3rd faculty of medicine , charles university in prague , czech republic . \nthe structured assessment included a questionnaire , anthropometric examination and blood sampling for biochemical analysis .\nhigh - resolution b - mode carotid ultrasonography ( using phillips iu22 ultrasound ) was performed to measure the cimt of the distant wall for 1 cm lengths of the carotid bifurcation and the internal carotid and right and left common carotid arteries .\nthe mean cimt values of 10 sites were combined in an unweighted average to produce an overall cimt .\nthe upper normal limit of cimt was set to 0.7 mm [ 12 , 13 ] .\nthe patient history of coronary heart disease and ischemic stroke was obtained from medical records .\nthe clinical and demographic characteristics of gck mutation carriers and control individuals were compared using welch 's two - sample t - tests ( continuous variables ) and fisher 's exact tests ( categorical variables ) .\nmixed linear regression models with cimt , blood pressure , and serum creatinine as outcomes were used to estimate and test the adjusted effects of gck mutation status . age , gender , and mutation status\nno significant differences in baseline characteristics were found between patients and control individuals , with the exception of fasting blood glucose ( gck - mody 7.6 mmol / l , sd 1.2 ( 136.4 mg / dl ) ; controls 5.3 mmol / l , sd 0.3 ( 95.4 mg / dl ) ; p < 0.0001 ) and glycated hemoglobin hba1c ( gck - mody 6.9% ( sd 1.0 ) , 52 mmol / mol ( sd 10 ) ; controls 5.7% ( sd 0.4 ) , 39 mmol / mol ( sd 3 ) ; p < 0.0001 ) ( table 1 ) .\nthe prevalence of smokers and hypertensive patients was similar in both samples ( p = 1 ) .\nthe measured cimt values for participants with and without gck mutations are shown in figure 1 .\nthe mean cimt was 0.707 mm ( range : 0.41.1 ) in gck - mody patients and was 0.692 mm ( range : 0.41.1 ) in healthy control individuals . according to the published recommendations [ 12 , 13 ]\nafter adjusting for age , gender , and family status , the estimated mean difference in cimt between patients and healthy individuals increased slightly to 0.049 mm ( 95% ci from 0.026 to 0.123 ; p = 0.19 ) . as expected , the estimated trends of mean cimt indicated a moderate increase in cimt with age and mutation status ( see regression lines plotted in figure 1 ) .\ncarotid plaques ( local intima - media thickening exceeding 1 mm and protruding into the lumen ) were identified in 7 ( 25.9% ) patients and 3 ( 12.5% ) control individuals ( p = 0.1 ) , but all of these plaques were hemodynamically insignificant . \nmyocardial changes typical of ischemic heart disease described on echocardiography and/or ecg were detected in three of 27 patients with gck - mody and two of the 24 healthy control individuals ( p = 0.866 ) .\nthree study participants had suffered from myocardial infarction ( two with gck - mody and one control individual ) ( p = 0.895 ) in the past , and two had suffered from ischemic stroke ( one with gck - mody and one control individual ) .\na similar proportion of participants ( 35% ) from both groups were treated for hypertension with one or more antihypertensive drugs .\nfour of the 27 patients with gck - mody ( 14.8% ) were treated with oral hypoglycemic agents , and one was treated with insulin .\nto the best of our knowledge , the present study is the first case - control study including the cimt measurements of gck - mody patients older than 35 years .\nthe results are consistent with the mild natural course of gck - mody and confirm that gck mutation is not associated with an increased risk of developing macroangiopathic complications .\nthe 95% confidence interval of the cimt difference , adjusted for age , family , and gender , is 0.026 to + 0.123 mm , indicating that the possible increase in cimt associated with gck mutation is low and most likely clinically insignificant .\nthe absence of serious chronic microvascular complications in gck - mody was observed by page et al . and\nvelho et al . [ 16 , 17 ] , who described proliferative retinopathy in less than 4% , proteinuria in 6% , and peripheral neuropathy in 5% of patients with hyperglycemia at more than 5 years after diagnosis .\na major problem with assessing diabetic complications in those patients is the differentiation between patients who only have gck - mody and those who develop type 2 diabetes in addition to gck - mody .\nit is generally assumed that patients with gck - mody do not necessarily develop insulin resistance or dyslipidemia in the natural disease course , and their glucose tolerance remains stable over many years . nevertheless , carrying\na gck mutation does not protect against the development of type 2 diabetes , which occurs at a similar prevalence in gck - mody patients and in the general population . \nit has been reported that metabolic syndrome and insulin resistance are the major components of atherosclerosis risk in patients with diabetes and also in individuals without diabetes with insulin resistance [ 3 , 20 , 21 ] , whereas the role of hyperglycemia in cardiovascular disease associated with type 2 diabetes is less clear .\nin contrast with patients with type 2 diabetes , patients with gck - mody have mild hyperglycemia without other components of metabolic syndrome or insulin resistance . therefore , our study adds to the accumulating evidence that chronic mild hyperglycemia without additional components of metabolic syndrome has a milder effect on the development of macrovascular complications compared with the same glycemic levels associated with metabolic syndrome components .\nadmittedly , more subtle effects on cimt would remain undetected , as the present study is moderately sized .\nthe numbers of available patients in other studies are , however , comparable a detailed analysis of the effects of p.gly299arg mutation in the gck gene was limited to a single large pedigree , whereas another study reporting selected metabolic parameters and history data included 35 families , but these subjects were not examined at a single centre , and the data did not include cimt [ 16 , 17 ] .\nthus , the number of participants may reflect a compromise between the depth of the acquired data and the subjects ' willingness to undergo a complicated set of investigations . \npatients with gck - mody exhibit only a small increase in glucose levels after oral glucose loading .\nby contrast , patients with type 2 diabetes have relatively high 2-hour glucose levels ( as a proxy for postprandial glucose levels ) , indicating that postprandial glucose levels could be the most pathogenic glycemic factor for developing micro- and macrovascular complications .\nthe cimt has been shown to correlate more strongly with postprandial glycemia than with fasting hyperglycemia .\nadditionally , the serum hs - crp levels are lower in gck - mody patients than in patients with type 2 diabetes .\nhowever , a common variant in the pancreatic gck promoter has been shown to influence the risk of diabetes complications .\nshowed that the a allele at c.30g > a of gck was associated with an increased risk of coronary artery disease in not only patients with type 2 diabetes but also individuals who did not have diabetes , albeit with a much weaker association ( or = 1.27 ; 95% ci 1.021.59 ) . additionally , the snp rs4607517 , which is in linkage disequilibrium with c.30g > a , has been associated with fasting glucose in genome - wide association studies .\nthe association between components of the fasting glucose genetic risk score ( represented by five snps , including rs4607517 ) and cimt has been described with an increment of 0.0048 mm in carriers . in conclusion ,\nour data indicate that the natural course of mild lifelong hyperglycemia is associated with a low risk of developing diabetic macrovascular complications .\nhowever , patients with gck - mody should take steps to reduce the risk of developing classical type 2 diabetes in addition to gck - mody that is , avoid obesity and maintain a high level of physical activity .\nour data support a conservative therapeutic approach for hyperglycemia in nonpregnant patients with gck - mody .\nother risk factors for micro- and macrovascular complications should be treated according to present guidelines .", "answer": "aim . \n gck - mody is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia . \n the risk of macrovascular complications is considered low , but studies are limited . \n we , therefore , investigated the carotid intima - media thickness ( cimt ) as an indicator of macrovascular complications in a group of patients with gck - mody . \n methods . twenty - seven gck mutation carriers and 24 controls recruited among their first - degree relatives \n were compared , all aging over 35 years . \n the cimt was tested using a high - resolution b - mode carotid ultrasonography . \n medical history , anthropometry , and biochemical blood workup were obtained . \n results . \n the mean cimt was 0.707 0.215 mm ( mean sd ) in gck mutation carriers and 0.690 0.180 mm in control individuals . \n when adjusted for age , gender , and family status , the estimated mean difference in cimt between the two groups increased to 0.049 mm ( p = 0.19 ) . \n no difference was detected for other characteristics , with the exception of fasting blood glucose ( gck - mody 7.6 mmol / l 1.2 ( 136.4 mg / dl ) ; controls 5.3 mmol / l 0.3 ( 95.4 mg / dl ) ; p < 0.0001 ) and glycated hemoglobin hba1c ( gck - mody 6.9% 1.0% , 52 mmol / mol 10 ; controls 5.7% 0.4% , 39 mmol / mol 3 ; p \n < 0.0001 ) . \n the frequency of myocardial infarction and ischemic stroke did not differ between groups . \n conclusion . \n our data indicate that the persistent hyperglycemia in gck - mody is associated with a low risk of developing diabetic macrovascular complications .", "id": 707} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmultiple sclerosis ( ms ) , received its name in 1955 , is an inflammatory disorder of brain and spinal cord where in body 's immune system incorrectly attacks its own central nervous system ( cns ) , causing variable and unpredictable symptoms ( some examples including slurred speech , blurred vision , loss of balance , poor coordination , tremors , numbness , extreme fatigue , problems with memory and concentration , paralysis , and blindness ) .\neven though a lot of advances have been made in past few decades , exact causes of this disorder remains unknown(environmental factor combined with genetic predisposition ) .\nthere is a high cost associated with this disorder and it reduces life expectancy as well as quality of life .\nunfortunately , there is no cure for ms , and most of the current drugs available in the market help treat the symptoms .\nms is not the same in any two people who have it , since the underlying cause is demyelination ( along with axon degeneration ) , which can target any brain area , resulting in a broad range of clinical symptoms ( compston and coles , 2002 ; alastair compston et al .\nin addition , brain lesions can sometimes outnumber the clinical symptoms by as much as 10:1 , and lesions in noncritical areas may not result in obvious functional deficits , even if brain function is in fact altered .\nthere are four subtypes of the disease - relapsing - remitting ms , primary progressive ms , secondary progressive ms and progressive relapsing ms , which differ in relapse rate , clinical symptoms , trajectory , underlying causes and approaches to disease management .\ncombined all these aspects of the disease ( various locations for demyelination , clinically silent timeline , and a highly variable disease course ) make the approach to care and treatment complex ( compston and coles , 2008 ; trapp and nave , 2008 ) .\ncurrent behavioral and imaging methods used to assess disease severity are insufficient by themselves to allow confident prediction of disease progression .\nthe addition of functional modeling ( modeling that correlates the functional loss to disease progression ) and objective functional measurements ( imaging as well as other assessments combined with disease status ) may greatly improve such prediction .\ncurrently , magnetic resonance imaging ( mri ) along with clinical manifestation of the disease are used as clinical tools for diagnosing ms ( filippi and grossman , 2002 ) . the 2010 revision to the mcdonald diagnostic criteria ( polman et al . ,\n2011 ) uses a combination of lesion and clinical attacks for the most confident diagnosis of ms .\nlesions must be disseminated in time or space or have positive identification from cerebral spinal fluid ( csf ) measure ( lublin et al . , 2014 ) .\nunfortunately , discrepancy still exists between clinical symptoms and structural measurements , because of the poor correlation between the presence of lesions and symptoms .\nthe two common measures used for diagnosis and monitoring with mri are hyperintense lesions on dual - echo mr , which is a nonspecific measure of macroscopic tissue injury , and enhanced abnormalities on t1 lesion weighted images , which is a measure of lesions .\nhowever , neither of these measures do provide extent and severity of inflammation , cellular component , or resultant tissue damage information ( filippi and grossman , 2002 ) .\nthus , there is a need for supplemental information from alternative techniques to have a more holistic approach .\nthere are emerging techniques that hold promise to quantify the brain imaging data , and relate that with clinical outcomes .\nsome promising examples include magnetization transfer mri ( quantitative and continuous measure of loss of myelin and reduction in axonal density ) , diffusion weighted mri ( quantitative measure of size , shape , geometry , and orientation of tissues ) , proton magnetic resonance spectroscopy ( mrs , provides measure of two major pathologic aspects of ms - the active inflammatory / demyelinating process and axonal injury ) , functional mri ( provides functional information about brain activation during motor , sensitive , and cognitive tasks ) , high field strength imaging ( ex 7 t mri , leads to improved signal - to - noise ratio , speed , and resolution in both mri and mrs ) and transcranial magnetic stimulation ( tms , highly sensitive technique to evaluate cortico - spinal conduction abnormalities in ms ) .\nsince t1 scan is transient , it should be only used in patients that have frequent mri , and should not be used for comparison between subjects . instead ,\ngiven the availability of multiple brain imaging modalities , the need still exists for creating a combined assessment tool .\nquite a few studies have attempted to combine various measures ( petzold et al . , 2006 ; daumer et al . , 2007 , 2009 ; castro - borrero et al . , 2012 ; sormani , 2013 ; giffroy et al . ,\nmultiple sclerosis severity scale ( msss ) was developed to relate expanded disability status scale ( edss ) to the disease duration .\nit has been shown that msss correlates with axonal biomarkers but not with glial biomarkers ( petzold et al . , 2006 ) .\nthis scale was tested on 195 ms patients to predict accrual of disability over time to see if current therapies have impact on disease severity over time .\npachner and steiner ( 2009 ) concluded that the current disease modifying drug therapies lack emphasis on disease severity .\nan online analytical processing tool was developed that can be used for prognosis of near term future course of an individual patient ( daumer et al . , 2007 ) .\nthis tool is based on matching algorithm ( using statistical analysis ) and contains data of 1,059 patients .\noutcome was to show the probable progression over time which can be useful for subjects , physicians , researchers and other professionals who counsel the patients . in an attempt to test the developing treatment methods , sormani ( 2013 ) explored the use of various biomarkers that can be used to predict the clinical response to interferon beta ( ifn- ) treatment .\nhe concluded with the need for precise , meaningful measures of disease progression , integrated with clinical measures to help with personalized treatment for ms .\na computational classifier was modeled that can be used for predicting short term course of ms ( bejarano et al . , 2011 ) .\nit combined clinical data , with mri and motor evoked potential ( mep ) , and it was found that the model did good job on predicting short time scale disability .\na description of the use of various potential biomarkers with their pros and cons was created .\nit ranges from markers for immunological activation , as well as markers for demyelination , axonal damage , oxidative stress , remyelination , glycoses , and details of specimen such as blood , urine , tears and csf ( bielecki et al . , 2010 ) .\n( 2010 ) concluded with a need for unification and standardization of results of various measurements and techniques .\nthere have been many advances in modeling and designing tools and predictive capabilities for ms .\n( 2015 ) studied 1,959 patients from 19952013 with clinically isolated syndrome and found that demographic and topographic characteristics had a low effect on prognostic factors for ms , while the presence of oligoclonal band ( oligoclonal bands are proteins called immunoglobulins and their presence indicates inflammation of the central nervous system ) had medium effect , and the number of lesions had the highest impact . in an another study ,\n2014 ) recruited 652 patients and studied them for prediction factors that can be classified as disseminated in time ( dit ) , disseminated in space ( dis ) , or both , and concluded that there is a need of more predictive factor combinations to help risk for ms .\nan analysis of 598 ms patients was performed in norway to determine factors responsible for life expectancy , and the conclusion was that high age at the onset was correlated with unfavorable prognosis ( riise et al . , 1988 ) . in another study on early prognostic features on the late course for ms in world war veterans\n, it was found that pyramidal and cerebellar scores are the best predictors ( kurtzke et al . , 1972 ) .\nwang et al . ( 2015 ) performed a study to combine in vivo biomarker using electrical vestibular stimulation and eye movement recording to measure evoked vestibular - ocular reflexed ( evor ) in 18 subjects with ms ( wang et al . , 2015 ) .\nthe goal was to measure the axonal conduction velocity to understand the myelin process and provide a way for assessing efficacy of novel reparative therapies in ms .\nthere still exists a need to for quantification , combination of various results from studies , and longer longitudinal studies .\nlastly , a computational approach will be necessary for various biological , clinical , imaging findings to form an integrative modeling system that encompasses grey matter pathology , myelin sheath aqueous layers , energy metabolism , and perhaps most importantly , multi - scale or integrated modeling .\nmy recent paper ( chaubey and goodwin , 2016 ) is a computational modeling study which makes it possible to make quantitative predictions about the degree to which electrical signals will move more slowly through axonal pathways as a function of how much of their myelin sheath they have lost as a result of ms ( using data from diffusion tensor imaging ( dti ) , and other modalities ) .\nthe paper identifies a new biomarker for network failure in ms that should improve our ability to predict and track loss of sensory , motor and cognitive function in the disease and a better way to measure the efficacy of new treatments .\nthe potential also exists to relate this slow down to disease progression , and eventually , to disease prediction , in which we could use the existing model to predict the disease symptoms in subsequent years . a study in my research center ( brain sciences center , va medical center ) used magnetoencephalography ( meg ) resting state recordings as a functional biomarker to classify ms and various other patient populations to their respective groups , by assessing synchronous neural interactions at high temporal resolution as a measurement of the dynamic synchronous neural interactions , an essential aspect of brain function ( georgopoulos et al . , 2007 ) .\nanother study used similar analysis in 50 ms patients ( 31 rrms , 15 spms , 4 ppms ) and 214 healthy controls ( carpenter et al . , 2011 ) .\nancova was performed at each of the 30,628 sensor pairs ( pccs ) using group ( ms , control ) as a fixed factor and age , gender and handedness as covariates .\nsimilar analyses were done using each ms phenotype ( rrms , spms , etc . ) as a factor and 300 ( out of 30,628 ) sensor pairs were found to have a significant group differences after correction for multiple comparisons .\nthere is a need to combine such objective measures of brain function with modeling techniques to improve assessment and prediction of the disease over what is possible using established methods . to list few direct advantages of these predictions : 1 )\nthese predictions can identify high - risk patients who require early and more aggressive therapies , 2 ) they can help patients with clinically isolated syndrome ( cis , one of the ms disease courses , refers to a first episode of neurologic symptoms , but it is not alone enough to have diagnosis of ms , as there needs to be two episodes disseminated in time or space ) to predict how likely and at what time frame the ms diagnosis is likely , 3 ) they can provide an individual plan for various subjects depending on their current status and symptoms ( bergamaschi and montomoli , 2016 ) .\nthere is a need for modeling to help direct research using testable predictions and fixing the current gap in knowledge .\nthere is enormous amount of data available , a lot of which is open access , and it is important to make sense of it all .\ncomputational modeling can be an essential tool to help make use and sense of all this data and lead to better understanding , diagnosis , prediction of various diseases , especially ms . as there is no cure for ms , most treatments typically focus on slowing the progression of the disease and managing symptoms .\nsince tissue destruction and disease onset begins much earlier than the actual clinical symptoms appear , it will be important to test future therapeutics to detect early axonal loss , axonal dysfunction and efficiency of these treatment methods .\nadvances in imaging technology and use of new techniques need to be established and validated to determine the success of remyelination and cessation of old damage .\nfinally , a combination of modeling will allow for prediction and better quality of life for people with ms .\nthere is a huge need for a reliable and personalized disease prediction model of ms .\nit would benefit patients with ms , as they can plan and select the best individualized treatment option .\nit would be helpful to the clinician working with patients , especially early stage patients , to help with selection of the best therapeutic treatment options .\nintegration of modeling , biology , clinical and imaging data can help provide more personalized and reliable monitoring of disease progression and in turn lead to better disease prediction .", "answer": "multiple sclerosis ( ms ) is a major cause of neurological disability in adults and has an annual cost of approximately $ 28 billion in the united states . \n ms is a very complex disorder as demyelination can happen in a variety of locations throughout the brain ; therefore , this disease is never the same in two patients making it very hard to predict disease progression . a modeling approach which combines clinical , biological and imaging measures to help treat and fight this disorder \n is needed . in this paper , i will outline ms as a very heterogeneous disorder , review some potential solutions from the literature , demonstrate the need for a biomarker and will discuss how computational modeling combined with biological , clinical and imaging data can help link disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism .", "id": 708} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe recently demonstrated that diabetes directly induced dental caries in rats and mice , although a direct association between the 2 was less evident and conflicting in humans [ 14 ] .\nwe demonstrated that dental caries were produced using noncariogenic diets with a low concentration of sugar in diabetic rodent models [ 57 ] , although many studies usually add large amounts of sugar to the diet to induce dental caries [ 8 , 9 ] .\nin addition , early studies on the production of experimental dental caries have reported the effects of physical properties of cariogenic diets with high concentrations of sugar on dental caries .\nthese studies mainly used finely ground cariogenic diet [ 1013 ] because it is more cariogenic compared to a coarsely ground diet in rodents .\nmoreover , hard and coarse foods have the ability to prevent caries [ 1417 ] .\nthus , modifying the dietary formulation may possibly enhance or reduce caries development in diabetic animals .\nhowever , no reports have investigated the effects of the physical properties of non - cariogenic standard diets on dental caries in diabetic animals . \ncurrently , 2 types of non - cariogenic standard diet formulations ( i.e. , powdered and pelletized diets ) are widely used in experimental rodents . in the present study ,\nwe compared the effects of these diets on the development of dental caries in a diabetic rodent model focusing on the difference in hardness between the powdered and pelletized diets .\nsix - week - old female f344 rats were supplied by japan slc , inc .\nthe animals were housed in stainless - steel cages at a temperature of 2026c and a relative humidity of 4070% under a 12/12 h light / dark cycle , that were ventilated with filtered fresh air . to prevent infection ,\nthe animals were allowed free access to tap water and fed with a widely used standard pelletized or powdered diet ( charles river formula 1 ( crf-1 ) ; oriental yeast co. , ltd . ,\nthe animals were handled according to the principles for all experimental procedures outlined in the guide for the care and use of laboratory animals prepared by our institution ( setsunan university ) and the japanese association for laboratory animal science .\nthe glucose levels in the fresh urine were measured semiquantitatively using urine test paper ( wako pure chemical industries , osaka , japan ) daily from day 1 to day 3 after dosing , once every week for 1 month after the first week , and once every month thereafter .\nthe blood glucose levels in the tail vein samples were also measured semi - quantitatively using the glucose oxidase method ( glutest e ; sanwakagaku , aichi , japan ) once every month from the fourth week after alloxan injection .\nblood samples obtained from the tail vein and fresh urine were collected from 1:00 to 4:00 p.m. the severity of hyperglycemia was defined as follows : normal , < 200 mg / dl ; mild , > 200 mg / dl ; moderate , > 300 mg / dl ; or severe , > 400 mg / dl . the severity of glycosuria was defined as follows : normal , < 100 mg / dl ; mild , > 100 mg / dl ; moderate , > 250 mg / dl ; or severe , > 500 mg / dl . the experimental design is shown in figure 1 .\nten rats , aged 7 weeks , were given a single dose ( 35 mg / kg body weight ) of alloxan ( sigma - aldrich japan , tokyo , japan ) via tail vein injection .\nthe dose of alloxan was determined as the given dose at which a rat survives for a long period after the onset of diabetic symptoms . after the confirmation of hyperglycemia and glucosuria following the dosing of alloxan ,\nfive rats were given a pelletized crf-1 diet ( diabetes - pelletized diet group ) and the remaining 5 rats were given a powdered crf-1 diet ( diabetes - powdered diet group ) .\nas a control , each of the 5 intact rats was fed a pelletized or powdered crf-1 diet ( control - pelletized diet group and control - powdered diet group ) .\nthe animals were euthanized by exsanguination under deep anesthesia at the end of the observation period .\nsubsequently , the mandible was removed and fixed in 10% neutral - buffered formalin ( ph 7.4 ) .\nafter a 24 h fixation , the occlusal , buccolingual , and proximal surfaces of all of the molar teeth were intensively observed under a binocular stereoscope .\nsoft x - ray images of the mesiodistal plane were taken under conditions of 35 kv and 2 ma for 4 min .\nthe molar teeth were classified into 5 groups according to caries characteristics by observing and analyzing the radiographs : no radiolucent change ( grade 0 ) , radiolucent area only on the occlusal surface of the crown ( grade 1 ) , radiolucent areas on occlusal surface and either of the mesiodistal surfaces of the crown ( grade 2 ) , radiolucent areas over the entire surface of the crown ( grade 3 ) , and radiolucent areas over most of the surface of the dental root ( grade 4 ) .\nthe mean score of the caries was used as indicator for comparing the severity of the carious lesions between the groups .\nafter soft x - ray examination , a histopathological examination was performed on the mandible in all of the rats .\nafter fixation with 10% neutral - buffered formalin , the sample was decalcified in a 5% solution of ethylenediaminetetraacetic acid 4 na ( edta 4 na ) for 2 weeks at 4c .\nafter decalcification , the specimens were trimmed , dehydrated in a sequential ethanol series using an automated processor , and embedded in paraffin wax .\nserial 7 m thick sections on the mesiodistal plane were made through the centers of all of the molars and then stained with hematoxylin and eosin for examination using light microscopy .\nthe severity of the caries lesion was graded as follows : slight , dentin caries localized in occlusal surface of dentin ; mild , dentin caries extended into the dental pulp with pulpitis and/or pulp necrosis ; moderate , dental crowns were partially decayed ; and severe , dental crowns were completely decayed ( only the molar roots remained ) .\nthe wilcoxon rank - sum test was employed to compare the differences in the mean scores of the caries lesions using soft x - ray examination between the groups .\nthe chi - square test was used to determine the caries incidence using soft x - ray examination and the incidence of histopathological lesions in each group of rats .\nsevere hyperglycemia ( > 400 mg / dl ) and glucosuria ( > 500 mg / dl ) continued from the day after alloxan injection to the last monitoring day in all of the rats in the alloxan - treated groups .\nin addition , the blood glucose levels ranged from 78 to 120 mg / dl ( normoglycemia ) , and the urine glucose levels were less than 100 mg / dl in the control groups . \ntypical macroscopic appearances of carious molars in diabetic rats are shown in figures 3(a ) , 3(b ) , and 3(c ) .\nmacroscopically , the dental caries developed mainly in occlusal fissures and were identified as partial coronal defects of the molars in alloxan - treated diabetic rats ( figure 3(b ) ) .\nthe carious lesions expanded horizontally , until the crown of the carious molar was completely invisible ( figures 3(b ) and 3(c ) ) . in contrast , control nondiabetic rats showed no changes in any of the molars ( figure 3(a ) ) . \nsoft x - ray images of the carious lesion in diabetic rats are shown in figures 3(d ) , 3(e ) , and 3(f ) . in all of the alloxan - treated diabetic rats ,\nradiographically , the dental caries progressed both horizontally and vertically . in diabetic rats fed with a pelletized diet ,\nthe carious lesion was mainly characterized as grade 2 ( figure 3(e ) ) or 4 type ( table 1 ) .\nin addition , the diabetic rats fed a powdered diet demonstrated carious lesions that were nearly of grade 4 type ( figure 3(f ) ) . in the control\nnon - diabetic rats , there was no change in the molar teeth ( table 1 , figure 3(d ) ) . \nthe histopathological characteristics of the carious lesion in diabetic rats are shown in figures 3(g ) , 3(h ) , and 3(i ) .\nhistopathological carious lesions were detected in the crown as eroded dentin with bacterial colonization in alloxan - treated diabetic rats . in diabetic rats fed with the pelletized diet , many of the molars were moderately affected and the dentin caries spread over a wide area of the dental crown ( figure 3(h ) ) . in the diabetic rats fed with the powdered diet , the dental caries were markedly worsened and the crowns were nearly completely decayed ( figure 3(i ) ) . \nthe incidence of caries teeth on the basis of each scoring in the soft x - ray examination is shown in table 1 .\nthe incidence of dental caries in the diabetic rats fed on both the pelletized and powdered diets was apparently higher ( p < 0.01 ) compared to the non - diabetic control rats ( table 1 ) . in the diabetic rats fed with the pelletized diet , 96.7% of their molar teeth were affected with dental caries , and the mean caries score was 2.7 .\nin addition , in the diabetic rats fed with the powdered diet , all of their molars ( 100% ) were affected with caries , and the mean caries score was 3.7 , which was significantly higher ( p < 0.01 ) than the diabetic rats fed with the pelletized diet ( table 1 , figure 4 ) .\nno radiolucent lesions were observed in any of the molars in control non - diabetic rats .\nthe incidence of histopathological carious lesions on the basis of each grade is summarized in table 2 .\nhistopathologically , the severity of the carious lesions in the diabetic rats fed with a powdered diet was significantly enhanced compared to the diabetic rats fed with the pelletized diet ( table 2 ) . in control non - diabetic rats , slight carious lesions , which were macroscopically and radiographically normal ,\nwere detected in a few animals ; however , there were no differences observed between the non - diabetic rats on the pelletized and powdered diets ( table 2 ) .\nthe physical properties of foods such as hardness , adhesiveness , and cohesiveness are closely related with the caries - producing potential [ 19 , 20 ] . moreover ,\nthe development of caries is known to be profoundly affected by food hardness , and hard and coarse foods can exert a detergent activity during mastication , which is effective in the prevention of caries [ 17 , 19 ] . furthermore , a lower degree of caries was reported in animals fed with the hardest food diet . in the present study , the severity of caries in diabetic rats was enhanced in the powdered diet group compared to the pelletized diet group .\nit was clear that food hardness affected the development of dental caries in diabetic rats fed on a non - cariogenic diet .\nhard foods are known to help flush away or neutralize undesirable material within the dental plaque and exert a cleaning effect on smooth surfaces by direct mechanical friction .\ntherefore , cariogenicity will be higher in diabetic rats fed with a powdered diet than in those fed with a pelletized diet . in this study , a high incidence and severity of dental caries was confirmed in the alloxan - treated diabetic rats fed with 2 types of standard diets with a low concentration of sugar .\nfurthermore , the mean caries score of the diabetic rats fed on the pelletized diet at 52 weeks after alloxan dosing in this study was almost 2-fold compared to animals at 26 weeks after alloxan dosing described in a previous report , strongly suggesting that the duration of hyperglycemia may affect caries development in diabetic animals . in this study ,\ndental caries developed and extended to all of the molars in diabetic rats fed on both the pelletized and powdered diets .\nthus , the effect of food hardness on the different diets in caries development in diabetic rats may become clearer when the dental caries mildly develop during the more early stages . in conclusion\n, food hardness could have an effect on the development of dental caries in diabetic rats , and appropriate consideration of the food formulation should be made in experimental caries studies using diabetic rodent models .", "answer": "we have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets ; however , many studies usually add large amounts of sugar to the diet to induce dental caries . \n moreover , the physical properties of cariogenic diets have been reported as an important factor in the formation of caries . \n the aim of this study was to clarify the effect of the hardness of non - cariogenic diets on the development of dental caries in diabetic rodents . \n seven - week - old female f344 rats were divided into 4 groups : intact rats fed with a standard pelletized or powdered diet and alloxan - induced diabetic rats fed with a standard pelletized or powdered diet . \n all of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue . \n dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets . \n moreover , the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group . in conclusion , food hardness is an important factor influencing the development of dental caries in diabetic rats .", "id": 709} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvestibular schwannoma ( vs ) usually arises within the internal auditory canal ( iac ) from either the superior or inferior vestibular nerve .\nthese tumors usually grow very slowly with the growth rate 0.66 to 2 mm per year6,7 ) . with time , they cause erosion of iac .\nthe location of tumor in iac was closely related in erosion of iac , tumor that arise laterally along the course of eighth nerve could tend to cause varying degree of erosion before they extend into cerebellopontine angel ( cpa ) cistern4 ) .\nalmost all vs usually widens iac only and could not invade the temporal bone beyond the confines of the bone of iac .\nin this report , we describe a patient without previously known bone disease who presented with aggressive temporal bone invasion of unilateral vs.\na 51-year - old male presented with progressive hearing loss of last 4 years and dizziness of few months duration .\nhe did not have a history of a head trauma or of any brain surgery . on admission , neurological and physical examination revealed left side deafness , no facial weakness , or no other low cranial nerve deficit like loss of gag reflex , uvular deviation , tongue deviation .\nthe patient did not have any known systemic disease of bone and family history or physical characteristics of neurofibromatosis .\nhis blood profile , including his serum calcium , phosphorus , and alkaline phosphates , was normal .\nct scan showed that the tumor mass had destructed iac completely and temporal bone to petrous apex , grown around the cochlea , reached the carotid artery in its petrous portion , extended to jugular foramen ( fig .\nwe noticed pneumatized area of opposite temporal bone corresponded to eroded area by tumor ( fig .\nthe tumor was a 43.83 cm sized , heterogeneous lobulated , well - defined mass with destruction of iac and extended to cpa cistern .\nthe tumor was confined to posterior fossa and not extended to meckel 's cave ( fig .\nthe combined translabyrinthine with retrosigmoid suboccipital approach was used for the resection of the tumor . at the first time of surgery , we removed the tumor piece by piece within temporal area with translabyrinthine approach , but we could not find facial nerve with this approach .\nso we performed additional retrosigmoid suboccipiral approach , and it allowed the exposure the lateral recess area easily and origin site of facial nerve from brain stem .\nafter detection of facial nerve with intraoperative facial nerve monitoring , we dissected facial nerve from proximal to distal area .\nthe dissection of the facial nerve within the temporal bone was very difficult , because the facial nerve was severely adhered to the tumor mass ( fig .\nthe tumor was extended to jugular foramen by destruction of superior wall of jugular foramen .\nthe consistency of temporal bone was felt to be normal and the colors and the consistency of the tumor were typical of vs. we successfully achieved total removal of tumor and preserved facial nerve in continuity .\nthe postoperative course was uneventful with normal facial nerve function and the vertigo was resolved .\nthe patient was good condition after 18 months of follow - up without cranial nerve dysfunction .\nhe also did not show any evidence of the recurrence or residual tumor in postoperative mri performed at 15 months of follow up .\nvs typically originates lateral to the glial - schwann junction , and this point is usually located within the iac , and thus can erode the iac . but the mechanism of widening of iac by a vs still unknown .\ntakada et al.5 ) hypothesized that the mechanism involved in the destruction of iac is as follows : 1 ) the repeated strokes of the tumor caused by brain pulsation gradually eroded the bony wall of iac ( especially , that of the posterior wall ) .\nthe apparently less destruction of iac in cases with mostly cystic large tumors might be due to the restriction of this pulsatile movement .\n2 ) increased cerebrospinal fluid pressure on the site had some influence on the mechanism of bone erosion as also does solidity of the tumor .\nthis case presented with aggressive pattern of invasion of temporal bone , which is more extensive than expected in case of unilateral vs. temporal bone destruction over iac in vs is very rare . to our knowledge\nfeghali and kantrowitz2 ) reported 4 cases of temporal invasion of unilateral vs , in which one cases had experienced previous schwannoma surgery .\nthey suggested that the invasion to temporal bone occurred through two mechanism in growth of vs. one of them was that the destruction of bone in the petrous apex can actually follow the pneumatized tracts when the cortex of the iac was eroded .\nthe second mechanism was that a thick membranous scar had \" trapped \" and confined the tumor within the temporal bone and separated it from the recurrent tumor in the cpa .\nwe examined various factors related in the excessive erosion of temporal bone in this patient . in this case , the patient showed no signs of osteoporosis and no abnormal laboratory findings including serum level of calcium , phosphorus and alkaline phosphatase .\nhistologic findings demonstrated typical nature of benign schwannoma , and there were not excessive unusual vascularity nor any malignant features .\nif cortex of iac was eroded , the tumor could grow into the temporal bone through the pneumatized area .\nbut we can not determine why this unilateral tumor first eroded cortex of iac and destructed temporal bone to the petrous apex before growing along the area of least resistance toward the cpa cistern .\ntrigeminal schwannoma usually widen meckel 's cave and extend into middle fossa and posterior fossa , may destruct petrous apex and grow into temporal bone .\nmri showed that the tumor was confined to posterior fossa and not extended to meckel 's cave . and\ntympanic segment is the most frequently involved3 ) , so temporal bone might be destructed .\nthe patient presented no facial palsy , no facial sensory change , and no facial pain .\nthe most common surgical approaches for vs is the translabyrinthine or suboccipital approaches1 ) . because of hearing loss and mass in temporal bone , we performed combined translabyrinthine with retrosigmoid suboccipital approach to detect the facial nerve earlier and remove the tumor in temporal bone . the facial nerve was severely compressed and irregularly distorted by tumor , bony edges , and crests along the invaded petrous apex .\ntemporal bone destruction beyond the cortex of iac in vs is very rare , which cause facial nerve compressed and distorted severely . during operation\n, it is very difficult to dissect and preserve the facial nerve because of uneven erosion of temporal bone .", "answer": "vestibular schwannoma ( vs ) usually present the widening of internal auditory canal ( iac ) , and these bony changes are typically limited to iac , not extend to temporal bone . \n temporal bone invasion by vs is extremely rare . \n we report 51-year - old man who revealed temporal bone destruction beyond iac by unilateral vs. the bony destruction extended anteriorly to the carotid canal and inferiorly to the jugular foramen . on histopathologic examination , \n the tumor showed typical benign schwannoma and did not show any unusual vascularity or malignant feature . \n facial nerve was severely compressed and distorted by tumor , which unevenly eroded temporal bone in surgical field . \n vestibular schwannoma with atypical invasion of temporal bone can be successfully treated with combined translabyrinthine and lateral suboccipiral approach without facial nerve dysfunction . \n early detection and careful dissection of facial nerve with intraoperative monitoring should be considered during operation due to severe adhesion and distortion of facial nerve by tumor and eroded temporal bone .", "id": 710} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlignocaine ( n - diethylaminoacetyl-2,6-xylidide ) was first synthesized by lofgen a swedish chemist in 1943 and was first introduced into clinical use in 1948 .\nlignocaine hydrochloride ( c14h22n2o.hcl ) is most soluble in water and so this is most commonly used injectable solution as local anesthetic agents .\nthe efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of action and intermediate duration of efficacy .\nlidocaine or lignocaine along with adrenaline has the advantage of a rapid onset of action .\nepinephrine ( adrenaline ) vasoconstricts arteries , reducing bleeding and also delays the resorption of lidocaine , almost doubling the duration of anesthesia . for surface anesthesia ,\nseveral available formulations can be used , e.g. for endoscopies , before intubations , etc .\ntopical lidocaine has been shown in some patients to relieve the pain of postherpetic neuralgia ( a complication of shingles ) , though not enough study evidence exists to recommend it as a first - line treatment .\nalthough not completely curing the disorder , it has been shown to reduce the effects by around two - thirds .\nlidocaine is also the most important class-1b antiarrhythmic drug ; it is used intravenously for the treatment of ventricular arrhythmias ( for acute myocardial infarction , digoxin poisoning , cardioversion , or cardiac catheterization ) if amiodarone is not available or contraindicated .\nlidocaine should be given for this indication after defibrillation , cardiopulmonary resuscitation , and vasopressors have been initiated .\na routine prophylactic administration is no longer recommended for acute cardiac infarction ; the overall benefit of this measure is not convincing .\nthe onset of action of lidocaine is about 4590 s and its duration is 1020 min .\nit is about 95% metabolized ( dealkylated ) in the liver mainly by cyp3a4 to the pharmacologically active metabolites monoethylglycinexylidide ( megx ) and then subsequently to the inactive glycine xylidide .\nmegx has a longer half - life than lidocaine but also is a less potent sodium channel blocker .\nthe elimination half - life of lidocaine is biphasic and around 90120 min in most patients .\nthis may be prolonged in patients with hepatic impairment ( average 343 min ) or congestive heart failure ( average 136 min ) .\nlidocaine is excreted in the urine ( 90% as metabolites and 10% as unchanged drug ) .\nbupivacaine ( 1-butyl-2 , 6- pipecoloxylidide ) was first synthesized in 1957 by ekenstam , a scandinavian chemist , and was first introduced into clinical use in 1963 .\nit is the longer side chain with four methylene groups on the piperidine ring that is responsible for the different properties of bupivacaine when compared to lignocaine .\nit has a molecular weight of 288.4 and an empirical formula of c18h28n2o and exists as white crystalline base with a melting point of 251258c .\nthe base is not soluble in water , but the acid salt , bupivacaine hydrochloride ( c18h28n2o.hcl ) is slightly soluble .\nthe rate of systemic absorption of bupivacaine and other local anesthetics is dependent upon the dose and concentration of drug administered , the route of administration , the vascularity of the administration site , and the presence or absence of epinephrine in the preparation .\nduration of action ( route and dose - dependent ) : 29 h. half - life in neonates is 8.1 h and in adults is 2.7 h. time to peak plasma concentration ( for peripheral , epidural or caudal block ) is 3045 min .\nthe rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered , the route of administration , the vascularity of the administration site , and the presence or absence of epinephrine in the anesthetic solution .\na dilute concentration of epinephrine ( 1:200,000 or 5 mcg / ml ) usually reduces the rate of absorption and peak plasma concentration of bupivacaine , permitting the use of moderately larger total doses and sometimes prolonging the duration of action .\nthe onset of action with bupivacaine is rapid and anesthesia is long lasting . the duration of anesthesia is significantly longer with bupivacaine than with any other commonly used local anesthetic .\nit has also been noted that there is a period of analgesia that persists after the return of sensation , during which time the need for strong analgesics is reduced .\nlocal anesthetics are bound to plasma proteins in varying degrees . in general , the lower the plasma concentration of drug the higher the percentage of drug bound to plasma proteins .\nthe rate and degree of diffusion are governed by ( 1 ) the degree of plasma protein binding , ( 2 ) the degree of ionization , and ( 3 ) the degree of lipid solubility\n. fetal / maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding because only the free , unbound drug is available for placental transfer .\nbupivacaine with a high protein binding capacity ( 95% ) has a low fetal / maternal ratio ( 0.20.4 ) . depending upon the route of administration ,\nlocal anesthetics are distributed to some extent to all body tissues , with high concentrations found in highly perfused organs such as the liver , lungs , heart , and brain .\npharmacokinetic studies on the plasma profile of bupivacaine after direct intravenous injection suggest a three - compartment open model .\nthe second compartment represents the equilibration of the drug throughout the highly perfused organs such as the brain , myocardium , lungs , kidneys , and liver .\nthe third compartment represents an equilibration of the drug with poorly perfused tissues , such as muscle and fat .\nthe elimination of drug from tissue distribution depends largely upon the ability of binding sites in the circulation to carry it to the liver where it is metabolized .\nafter injection of bupivacaine hydrochloride for caudal , epidural , or peripheral nerve block in man , peak levels of bupivacaine in the blood are reached in 3045 min , followed by a decline to insignificant levels during the next 36 h. various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic or renal disease , addition of epinephrine , factors affecting urinary ph , renal blood flow , the route of drug administration , and the age of the patient .\nthe half - life of bupivacaine in adults is 2.7 h and in neonates 8.1 h. in clinical studies , elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients .\namide - type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid .\npatients with hepatic disease , especially those with severe hepatic disease , may be more susceptible to the potential toxicities of the amide - type local anesthetics .\nwhen administered in recommended doses and concentrations , bupivacaine hydrochloride does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia .\nlocal anesthetics block the generation and the conduction of nerve impulses , presumably by increasing the threshold for electrical excitation in the nerve , by slowing the propagation of the nerve impulse , and by reducing the rate of rise of the action potential . in general ,\nthe progression of anesthesia is related to the diameter , myelination , and conduction velocity of affected nerve fibers .\nclinically , the order of loss of nerve function is as follows : ( 1 ) pain , ( 2 ) temperature , ( 3 ) touch , ( 4 ) proprioception , and ( 5 ) skeletal muscle tone .\nsystemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems ( cns ) . at blood concentrations achieved with normal therapeutic doses , changes in cardiac conduction ,\nhowever , toxic blood concentrations depress cardiac conduction and excitability , which may lead to atrioventricular block , ventricular arrhythmias , and cardiac arrest , sometimes resulting in fatalities . in addition\n, myocardial contractility is depressed , and peripheral vasodilation occurs , leading to decreased cardiac output and arterial blood pressure .\nrecent clinical reports and animal research suggest that these cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine\napparent central stimulation is manifested as restlessness , tremors and shivering progressing to convulsions , followed by depression and coma progressing ultimately to respiratory arrest . however , the local anesthetics have a primary depressant effect on the medulla and on higher centers\nin most of the studies 0.5% bupivacaine with adrenaline 1:200,000 and 2% lignocaine with adrenaline 1:200,000 were used as local anesthetic agents for third molar surgery as they are roughly equipotent .\nstudies have proved that bupivacaine is superior to lidocaine plus diflunisal in controlling postoperative pain after lower third molar surgery .\nsurprisingly there have been records of patients with no or mild pain at 8 h after the bupivacaine procedure was almost twice as many as after the lidocaine procedure , but is explained by the reason for preference being shorter duration of the anesthetic agent . in an australian study , most of the patients preferred the long - acting anesthetic agent bupivacaine .\nmany authors suggest that it seems reasonable that the combination of a long - acting local anesthetic with a weak analgesic is more efficient in relieving pain than the combination of a rather short - acting local anesthetic and a weak analgesic .\nbupivacaine is considered to have a therapeutic ratio of 2:0 while lignocaine in combination with adrenaline has a therapeutic ratio of 2:3 .\nhowever , it has shown that the injection route alters the relative toxicity of local anesthetics . in a study by de jong and bonin in 1980 they found out that the bupivacaine has a greater therapeutic ratio than lignocaine when used for surgical removal of impacted third molars .\nstudies have proved that long - acting bupivacaine can be safely administered for surgical removal of lower third molar and it does have a long period of nalgesia postoperatively compared to lidocaine , but the cardio depressant property of bupivacaine should be kept in mind and should be administered judicially .\neven studies have also shown that bupivacaine combined with methylprednisolone reduced the postoperative pain and swelling compared with the use of lidocaine and placebo , lidocaine and methylprednisolone , or bupivacaine and placebo .\nright now clinical trials are going on bupivacaine versus lidocaine anesthesia under university of british columbia 2014 with the idea that the longer duration of anesthesia offered by bupivacaine when administered preoperatively in elective outpatient hand surgeries , will offer more effective postoperative pain control compared to using lidocaine only .\nit has been found that both bupivacaine and lignocaine have their merits and demerits but beyond any doubt it has been proven by the clinical trials that bupivacaine provides better and prolonged analgesia and anesthesia post operatively during minor surgical procedures done at chair side along with surgical removal of impacted third molars .\nhence , bupivacaine can be regularly used as the anaesthetic solution along with adrenaline 1:200,000 for surgical removal of impacted third molars provided care being taken regarding the dosage and the cardiodepressant property of bupivacaine . right now , further studies are going on .", "answer": "one of the most important goal in minor surgical procedures is to achieve proper and sufficient anesthesia and analgesia preoperatively , intraoperatively and in the immediate postoperative period . \n several local anesthetic agents have been cited in the literature and studied . \n bupivacaine is one of the most common long - acting anesthetic agents being used for surgical removal of impacted third molars . \n lignocaine is one of the commonest short - acting anesthetic agents being used for the same procedure . in this review article , \n the analgesic and anesthetic abilities of the bupivacaine versus lignocaine have been reviewed while surgical removal of impacted third molars .", "id": 711} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nComparison of Mineral Element Content in a Functional Food Maca (Lepidium meyenii Walp.) from Asia and South America\n\nPaper sections:\n1. Introduction\nMaca (Lepidium meyenii Walp.) is an endemic highland crop of the Central Andes which is grown from central Peru to Bolivia and northwestern Argentina [1, 2]. This plant has great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases [3]. Maca roots have been traditionally used to increase the rate of fertility in both humans and livestock [4]. Over the past 20 years, interest in maca has increased in many parts of the world [5]. Commercial maca products have gained popularity as dietary supplements for aphrodisiac purposes and for increasing fertility and stamina [6]. Recently, maca industry develops fast in Yunnan Province, China. In Yunnan, until the end of 2010, maca growing and promotion areas reached 175\u2009hm2 and maca yield achieved 780\u2009t, taking up to 90% and 93%, nationwide [7].
Mineral elements in food are very important because the quality of many functional foods and medicines depends on the content and type of minerals [8]. In the US, national surveys show that micronutrient inadequacies are widespread and mineral supplement helps fulfill micronutrient requirements in adults and children [9]. Up to now, only limited studies on selected elements in maca from different origins have been carried out [10, 11]. Moreover, in some studies, no reference material had been certified for elemental analysis, so there has been doubt about accuracy of the determination.
In the present study, inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to determine the contents of eight elements (B, Co, Cr, Cu, Li, Na, Ni, and Zn) in maca samples, and a comparison was made between the samples from China and Peru.
\n\n2. Materials and Methods\nAll reagents used in the present work were of analytical reagent grade. Maca sample digests were prepared using HNO3 and H2O2 of ultrapure grade. Standard sample solutions of B, Co, Cr, Cu, Li, Na, Ni, and Zn obtained from Standard Material Center of China were used to make a mixed calibration curve in the range of 0\u2013400\u2009\u03bcg\u2009mL\u22121.
Ten maca samples were collected from four places of Yunnan, China, and four samples were from Peru. These samples were washed with deionized water thoroughly, dried to a constant weight, grounded into powder using an agate mortar, passed through a 60-mesh sieve, and stored in the plastic bags. 500\u2009mg of each maca sample was weighed into an acid washed Teflon digestion tube. 8\u2009mL of HNO3, 2\u2009mL of H2O2, and 1\u2009mL ultrapure water were added to the vessel.
Samples were digested in a microwave dissolver (Ethos One, Milestone, Italy) equipped with PTFE vessels. A three-step program was applied to the samples (Table 1). The extract was transferred into a cuvette and made up to 25\u2009mL with ultrapure water.
Simultaneous multielement detection of B, Co, Cr, Cu, Li, Na, Ni, and Zn was performed with ICP-OES (ICPE-9000, Shimazu, Japan). The optimal instrumental conditions for ICP-OES are shown in Table 2. The emission wavelengths and detection limits for each element are shown in Table 3. Every sample was measured with three replicates. Blank experiments were prepared in the same way.
To ensure the precision of the experiment, the certified reference material GBW10028 (dried herb powder Astragalus membranaceus) was used for validation of the method (Table 4). The relative standard deviation (RSD) was found to be below 8%, and the recoveries range from 92% to 109%, which proved that this method was accurate and precise.
\n\n3. Results and Discussion\nContents of B, Co, Cr, Cu, Li, Na, Ni, and Zn in maca samples are shown in Table 5. All element contents were determined on a dry weight basis.
Boron is essential for humans. Boron affects fat and lipid metabolism, minerals and mineral metabolism, vitamin D, and bone development [12]. Our B values in maca from China and Peru were 8.1\u201321\u2009mg\u2009kg\u22121\u2009dw and 6.6\u201312\u2009mg\u2009kg\u22121\u2009dw, respectively, which were in agreement with that reported in the literature (8.8\u2009mg\u2009kg\u22121\u2009dw) [13].
Cobalt is an essential micronutrient in the form of vitamin B12, but cobalt is toxic in larger doses or long-term exposure at a low level. The adverse effects of cobalt relate to various organs and tissues and may include a possible carcinogenic potential [14]. Chromium can induce the oxidative stress and genotoxicity in chromium exposed population [15]. Lithium appears to play an especially important role during the early fetal development [16]. The contents (mg\u2009kg\u22121\u2009dw) of Co, Cr, and Li were, respectively, <0.023, <1.1\u20133.5, and 0.020\u20130.17 for the samples from China and <0.023, <1.1\u20132.3, and 0.035\u20130.063 from Peru. Up to now, there was no other report on the contents of Co, Cr, and Li in maca.
Copper plays role as a cofactor for numerous enzymes in humans. Its compounds show vast array of biological actions, such as anti-inflammatory, antiproliferative, and biocidal activities [17]. Cu contents in the samples from China (2.5\u201331\u2009mg\u2009kg\u22121\u2009dw) were higher than the samples from Peru (<2.1\u2009mg\u2009kg\u22121\u2009dw). Published data available on Cu in maca from China were 4.0\u201332\u2009mg\u2009kg\u22121\u2009dw [10, 11, 13, 18], while those from Peru were 1.5\u201362\u2009mg\u2009kg\u22121\u2009dw [10, 11, 19\u201322].
Sodium is an essential element. In mammals, sodium concentrations in blood are held high by strict homeostatic mechanisms [23]. Na in the samples from China was in the range <30\u20132600\u2009mg\u2009kg\u22121\u2009dw which is similar to the value (67\u20132400\u2009mg\u2009kg\u22121\u2009dw) in maca from China in literatures [11, 13, 18]. However, our data on Na in the samples from Peru (<30\u201341\u2009mg\u2009kg\u22121\u2009dw) are lower than the values reported (110\u2013190\u2009mg\u2009kg\u22121\u2009dw) in the literatures [11, 19\u201322].
Nickel compounds have showed an increased risk of lung and nasal cancer in humans [24]. The contents of Ni in the samples were 0.085\u20134.5\u2009mg\u2009kg\u22121\u2009dw from China and 0.68\u20131.7\u2009mg\u2009kg\u22121\u2009dw from Peru. However, higher value (11.3\u2009mg\u2009kg\u22121\u2009dw) was found in the literature on the maca from China [13].
Zinc is essential for a number of physiological functions and plays a significant role in many enzyme actions in the living systems [25]. Zn contents in samples were found to be 19\u201339\u2009mg\u2009kg\u22121\u2009dw from China and 27\u201339\u2009mg\u2009kg\u22121\u2009dw from Peru, which were in accordance with the values for maca in literature available (25\u201389\u2009mg\u2009kg\u22121\u2009dw from China and 16\u201358\u2009mg\u2009kg\u22121\u2009dw from Peru) [10, 11, 13, 18\u201322].
\n\n4. Conclusions\nThe contents of eight elements of maca collected from China and Peru were determined. Cu contents in all of the maca samples from China, as well as Na contents in two samples from China, were remarkably higher than those values in other samples.
", "answer": "Contents of eight mineral elements in maca (Lepidium meyenii Walp.) from China and Peru were determined by inductively coupled plasma optical emission spectroscopy. Cu contents in maca samples from China (2.5\u201331 mg kg\u22121 dry weight, dw) were higher than the samples from Peru (<2.1 mg kg\u22121 dw). Na in two samples from China was found to be significantly of high content (2400 and 2600 mg kg\u22121 dw). The contents (mg kg\u22121 dw) of B, Co, Cr, Li, Ni, and Zn were, respectively, 8.1\u201321, <0.023, <1.1~3.5, 0.020\u20130.17, 0.085\u20134.5, and 10\u201339 for the samples from China, while being 6.6\u201312, <0.023, <1.1~2.3, 0.035\u20130.063, 0.68\u20131.7, and 27\u201339 for the samples from Peru.", "id": 712} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nover the last few years , the number of people infected with multidrug - resistant bacteria has been rising in a number of countries , among them germany . as a characteristic feature ,\nthis inhibits the efficacy of antibiotic treatment , with serious consequences for the health of infected individuals , the utilization of resources in the health care sector and the availability of resources in the economy in general . following an infection with multidrug - resistant bacteria ,\na number of effects may arise , each representing an economic cost : first , an individual will suffer from the risk of severe impairment of her health , including premature death .\nnext , appropriate treatment will take more time to produce the desired health outcome or will require more resources which must be diverted from other uses in the health care sector .\nin addition , the economy will incur losses in productivity whenever infected individuals belong to the workforce .\nfinally , aggravating these already serious consequences , infected individuals may spread multidrug - resistant bacteria , thus inflicting harm on other individuals and increasing the economic cost to society .\na first objective of the present contribution is to work out in more detail the economic effects which an infection or a colonization with multidrug - resistant bacteria may bring about .\nbuilding on this account , it will be argued that the status quo is inefficient .\nnext , an approach will be outlined which can be used to determine whether strategies to prevent or to reduce infections with multidrug - resistant bacteria provide a net benefit to society . in order to be able to implement a strategy that has been shown to be advantageous in this sense ,\nin essence , both objectives require a regional management of multidrug - resistant bacteria . by taking into account the entire health care sector within a region\nin order to carry out the tasks outlined above , it is important to be clear about how to assess the costs and benefits associated with strategies to prevent or reduce infections with multiresistant bacteria .\nfurthermore , the range of effects which need to be taken into account will depend on the perspective of the analysis . more specifically , while the ( in-)efficiency of the status quo or of an intervention can only be evaluated from the perspective of society , the issue of ( in-)appropriate incentives must be judged from the individual perspective . first , it is helpful to distinguish three types of costs .\ndirect costs represent the monetary value of resource utilization that takes place due to the production and consumption of health care .\napart from the cost of health care itself , this also includes any cost incurred by the patient in order to receive care , e.g. , travel costs .\nthe next type is given by indirect costs which cover the productivity losses , also valued in monetary units , due to illness or premature death .\nfinally , intangible costs capture the loss in utility or welfare for the patient which results from a reduction in her health status ( including death ) . in comparison with the other two types , intangible costs are more difficult to measure because it is necessary to develop a valuation from scratch .\nintangible costs can be measured either in monetary units ( i.e. , as willingness - to - pay ) or in other units such as quality - adjusted life years ( qalys ) .\nnext , strategies which aim to prevent infections with multidrug - resistant bacteria or to control their impact will usually involve a reduction in the associated costs . relying on a similar categorization as on the cost side\n, these benefits may turn up either as direct benefits , or as indirect benefits , or finally as intangible benefits . whereas direct benefits ( or indirect benefits ) accrue as reductions in direct costs ( or indirect costs ) , intangible benefits arise from improvements in health status or an extension of length of life . from the individual perspective of an economic unit such as , e.g. , a physician , an insurer , or a patient\n, it makes sense to take into account only those costs and benefits which accrue to the unit itself .\nthus , a decision is individually rational if it maximizes benefits over costs for the unit , thereby reaping the greatest net benefit .\nin contrast , the societal perspective takes into account the costs and benefits of all decision units .\nhence , a decision is rational from the perspective of society , or efficient for short , if it maximizes the net benefit that accrues to society . otherwise , it is inefficient and it is at least possible to make everyone better off by moving to an efficient decision .\nit is important to realize that both the perspectives are necessary to explain why inefficient decisions involving a waste of resources are taken and how they can be improved upon . according to a basic assumption that will also be imposed below\n, economic units always act individually rational , i.e. , they always maximize their own net benefit .\nsimple though it is , this assumption nevertheless can be quite helpful in explaining inefficient decisions .\nmore precisely , such decisions are likely to occur whenever the associated costs and benefits do not fall exclusively on the unit who takes them . \ne.g. , patients infected with multidrug - resistant bacteria are likely to receive inefficient health care if the providers have no incentive to take into account all the costs and benefits associated with the treatment they provide . applying the societal perspective\nprovides the only way to identify those strategies to prevent or control infections that are efficient . in order to promote their implementation , it is essential to modify the incentives which the providers of health care face such that applying an efficient strategy is in their own interest , i.e. , becomes individually rational . as claimed above , this demonstrates that both the societal perspective and the individual perspectives of the relevant players must be taken into account in order to arrive at an efficient provision of health care to patients infected with multidrug - resistant bacteria .\nindividuals who are colonized with multidrug - resistant bacteria but not yet infected usually do not suffer from any immediate consequences . however , there are substantial risks involving serious medical problems and economic costs , both for the individuals themselves as well as for other individuals who get in touch with them .\nfirst , there is the risk of developing an infection , imposing direct and intangible costs and possibly also indirect costs as outlined above .\nthe available studies , usually focusing on one type of bacteria and on a single disease , clearly demonstrate a considerable increase in length - of - stay and in direct hospital costs , , , , .\neven though the reductions in health status due to an infection with multidrug - resistant bacteria are less well documented , the associated rise in mortality indicates that intangible costs may well turn out to be very high , , .\nat the same time , individuals colonized with multidrug - resistant bacteria put other individuals at risk because their presence increases the probability that further colonization will take place .\nan analysis of the costs of multidrug - resistant bacteria from the societal perspective must take these costs into account as well .\neconomically speaking , they represent external costs because the colonization of one individual may exert a negative impact upon the health status of other individuals , .\nin fact , the external effects may reach very far , both with respect to the number of individual s concerned and over time .\nconsider the use of antibiotics : even with proper use in treatment , eventually resistant bacteria will turn up .\nhowever , antibiotic misuse on the part of either health care providers or patients substantially accelerates the evolution of resistant strains .\nthus , a flawed treatment of patients today imposes a cost on future patients . in economic terms ,\nefficacy of antibiotic treatment can be viewed as a common social good which , due to wrong incentives for the major players in the health care sector , suffers from the tragedy of the commons . in order to move towards a solution of the current problems with multidrug - resistant bacteria , it is necessary to identify strategies for improving the provision of health care . in a further step\n, care must be taken to make sure that promising strategies will also be implemented by the relevant actors . applying both steps in a systematic manner regularly and based on appropriate empirical data to check available strategies to prevent or control infections , one obtains a management of multidrug - resistant bacteria .\ngiven the problems of the status quo as outlined above , a change from simply dealing with multidrug - resistant bacteria ad hoc to a proper management can be expected to result in a substantial reduction in the associated costs for society . as a first step ,\nit is necessary to evaluate the costs and benefits to society arising from strategies to prevent infections with multidrug - resistant bacteria .\nstrategies that confer a net benefit to society improve on the current provision of health care and contribute to attaining the goal of an efficient management .\nobserve that the term strategy is defined in a narrow sense : in particular , it refers to a specific group of patients receiving care from a specific provider at a specific place .\nthus , if the benefits of , e.g. , a screening strategy exceed the associated costs , it is nevertheless possible that a further modification , for example by focusing on a different group of patients , may provide an ever higher net benefit to society .\nthere are good reasons to tackle these tasks within a regional management of multidrug - resistant bacteria .\nas its name suggests , a regional management has a clear focus on a specific region but implies no further restrictions otherwise .\nthus , it represents a comprehensive approach which is not confined to a single branch of the health care system . furthermore , in view of the problems outlined above it seems necessary to adopt a regional management because such an approach offers a unique opportunity to apply the perspective of society to strategies to prevent or control infections with multidrug - resistant bacteria .\nthis includes the setup and the continuous maintenance of a database relating to multidrug - resistant bacteria in order to record the prevalences of colonized individuals or infected patients as well as other relevant data .\na major objective would be to take into account the entire process of the development and also the spread of colonization and infections with multidrug - resistant bacteria . in some contrast to the prevailing approach with its focus on hospitals and on the control of infections , a regional management offers the prospect to recognize both the contribution of other health care providers and of strategies to prevent infections in order to deal with infections with multidrug - resistant bacteria in a manner that provides a maximum net benefit to society .\nat present , a major problem is that appropriate data on the costs of colonization with multidrug - resistant bacteria are not available . to be sure ,\nnevertheless , there are still no or at least no systematic data on some of the cost effects explained above . referring to infections with multidrug - resistant bacteria ,\nthis is true for the direct costs outside of hospitals as well as for the intangible costs due to a reduction in length of life or a deterioration of health status .\nin addition , there is no evidence on the probabilities with which colonized individuals develop an infection or cause other individuals either to be colonized or infected with multidrug - resistant bacteria .\nthese data would need to be collected with respect to the type of bacteria ( pathogen ) and possibly also with respect to individual attributes such as , e.g. , age or prevailing chronic diseases .\nnote that the lack of data on some important cost effects also has further implications . since the benefits of strategies to prevent or control infections arise primarily as reductions in the direct , indirect or intangible costs of multidrug - resistant bacteria , the full benefits to society are not known either . more specifically\n, there is a lack of data on the impact of efforts to prevent infections , and also on the valuation of the corresponding health effects by the affected individuals . in order to explain the present scale of infections with multidrug - resistant bacteria in germany , it is necessary to investigate the incentives of health care providers to employ strategies to prevent or control infections .\nconsider a health care provider who applies a screening test to patients deemed at risk such that patients will be isolated until the result becomes available and will be sanified if the test yields a positive result . in many instances , for the provider\nthis means incurring a certain cost with the prospect of only a small expected benefit : first , the remuneration may be insufficient ( perhaps even nil ) and/or the strategy may not generate enough cost savings for the provider .\nthe latter reason applies , e.g. , to ambulatory physicians because the higher cost of treatment due to an infection will occur primarily in hospitals .\nfurthermore , the additional benefits due to averted infections of other individuals will have no direct effect on the provider under consideration either .\na similar statement applies to the careful and cautious therapy with antibiotics which may also contain the development and the spread of multidrug - resistant bacteria : again , the cost falls primarily upon the prescribing physician whereas the benefit turns up elsewhere in society . even though it is not possible currently to describe the economic impact of colonization with multidrug - resistant bacteria in full , the lack of sufficiently strong incentives for health care providers\ncan safely be taken to imply that too little effort is devoted to the prevention or the control of infections . as a gauge ,\nconsider the costs and benefits to society of strategies to prevent or control infections with multidrug - resistant bacteria : as argued above , health care providers implementing such strategies will usually reap only part of the associated benefit while bearing the full cost .\ntherefore , the incentives facing health care providers are too weak to induce them to provide efficient care with respect to the protection from infections with multidrug - resistant bacteria . in turn\n, this implies that , from the perspective of society , there will be too many infections imposing an overall cost that is unnecessarily high . if a strategy to prevent infections with multidrug - resistant bacteria conferring a net benefit to society has been identified , the next task is to make sure that it will be implemented .\nin essence , this means setting appropriate incentives : the net benefit to society needs to be distributed among the relevant actors in a manner such that it is individually rational for everybody to apply the strategy .\nmore specifically , this implies an appropriate remuneration of health care providers , covering at least their own cost due to the effort to prevent or control infections with multidrug - resistant bacteria .\nmoreover , it may make sense to promote the cooperation among different sectors of the health care system , given that multidrug - resistant bacteria turn up not only in hospitals but also in ambulatory care or in nursing homes . applying\na regional management in a suitable manner also offers the prospect of overcoming the tragedy of the commons problem that besets the current approach to multidrug - resistant bacteria . by implementing the perspective of society in an entire region\n, it will be possible to take into account most of the substantial cost effects that are now external . improving surveillance as well as providing reliable information on the appropriate use of antibiotics may help to improve the efficacy of treatment for future patients . in this sense\n, a successful regional management may also contribute to save costs in the health care sector and to improve the health of patients in the future .\nthe current provision of health care to individuals who are colonized or infected with multidrug - resistant bacteria suffers from a number of shortcomings due to , e.g. , a lack of data and inappropriate incentives for providers .\nimplementing suitable strategies to control or prevent infections offers the prospect of reducing the costs associated with multidrug - resistant bacteria substantially , either by improving the health status of patients or by easing the financial burden on the health care system . for several reasons ,\na regional management represents an approach that can be trusted to improve on the status quo and to reap substantial net benefits for society by better dealing with the problems caused by multidrug - resistant bacteria .\nit is true that building up and maintaining a regional management of multidrug - resistant bacteria will involve a considerable cost .\nhowever , given the high costs of the status quo which will continue to rise unless precautionary measures are taken , this cost will be more than offset by the benefits that can be reaped by implementing efficient strategies to prevent or control infections .\na regional management of multidrug - resistant bacteria represents the first step towards a better integration of the health care system .\nif this step is taken successfully , it may also act as a role model for dealing with other problems in the provision of health care . at any rate\n, the potential benefits appear to be sufficiently high to more than justify embarking on this first step .", "answer": "the increasing number of people who are colonized or infected with multidrug - resistant bacteria imposes a high economic burden on society which includes the negative impact on health status as an intangible cost . \n an economic analysis leads to the conclusion that currently too little is done to prevent or control infections . \n the reasons include insufficient incentives for health care providers , a lack of reliable data on both the prevalence and the effects of infection , and a lack of coordination among the different branches of the health care sector . \n a regional management of multidrugresistant bacteria which does not focus on a single branch but rather on the health care sector overall can achieve a substantial reduction in the number of infected people and of the associated economic cost for society .", "id": 713} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 69-year - old woman with a transitional cell carcinoma in the renal pelvis underwent a laparoscopic nephroureterectomy .\nthe patient had a history of hypertension , and had no history of allergy or previous exposure to indigo carmine .\nanesthesia was induced with thiopental 400 mg and vecuronium 10 mg , and maintained with 2% sevoflurane after tracheal intubation .\na 20-gauge catheter was inserted into her left radial artery to monitor continuous arterial pressure . during the operation ,\nthe patient 's vital signs were stable , with blood pressure ( bp ) 100 - 130/70 - 95 mmhg , heart rate 62 - 88 bpm , and spo2 98 - 100% .\ntwo hundred minutes after the induction of anesthesia , she received a bolus injection of 40 mg indigo carmine ( sodium indigotindisulfonate ; korea united pharm . ,\none minute later , her bp suddenly decreased from 120/85 mmhg to 50/30 mmhg , but heart rate remained at 80 - 90 bpm .\nthere was no evidence of massive blood loss or electrocardiographic changes prior to the hypotensive episode , and there were no skin rashes , angioedema , or any sign of bronchospasm during the hypotensive episode .\nshe was immediately administered ephedrine 20 mg and phenylephrine 0.3 mg , which restored her bp to 120/75 mmhg .\nten days later , a 73-year - old man who underwent a radical retropubic prostatectomy under general anesthesia experienced severe hypotension after administration of indigo carmine .\nninety minutes after anesthesia induction , he received an injection of 40 mg indigo carmine , and then bp decreased from 110/65 mmhg to 60/35 mmhg without any skin rash or urticaria .\nhe was administered ephedrine 40 mg and phenylephrine 0.3 mg , which restored his bp to the pre - indigo carmine level .\nfollowing these adverse events , we decided to dilute indigo carmine in normal saline and to administer it slowly over five minutes .\nthe patient had a drug allergy to saridon - a ( roche korea , seoul , korea ) , which contains acetaminophen , anhydrous caffeine , and isopropylantipyrine .\ntwo hundred minutes after induction , she was administered 40 mg indigo carmine diluted in 20 ml of saline over five minutes . a sudden drop in bp\nwas observed ; from 125/72 mmhg to 45/30 mmhg , and injection of ephedrine 30 mg restored her bp within three minutes . following this third episode of hypotension , we suspected a manufacturing error and checked the lot number of indigo carmine .\nwe discarded all of the indigo carmine with lot number 001 , used in our third patient , and decided to use another lot number , 002 .\ntwo weeks later , two additional patients experienced severe hypotension following administration of indigo carmine .\nthe first , a 68-year - old man , underwent transurethral bladder tumor resection under general anesthesia .\nfive minutes later , his bp dropped from 128/75 mmhg to 65/43 mmhg , and injection of phenylephrine 0.3 mg restored his bp .\nanother patient was a 77-year - old man who underwent transurethral resection of the bladder .\nspinal anesthesia was induced with hyperbaric bupivacaine 11 mg at the l4 - 5 level .\nafter forty - five minutes , he received indigo carmine , and then his bp decreased from 110/65 mmhg to 60/35 mmhg .\nafter administration of 15 mg ephedrine , his vital signs remained stable throughout the rest of the procedure .\nthe company 's director informed us that lot numbers 001 and 002 were manufactured with the same raw materials , and the manufacturer provided us with indigo carmine of lot number 906 , which to date has not been associated with any such adverse events .\nthe raw materials used to manufacture indigo carmines were analyzed , including their crystalline status , thermo - physiochemical properties and particle size distribution , all of which are required analytical criteria for drug manufacture , as determined by the korea food and drug administration .\na comparison of the raw materials used to manufacture lot numbers 002 and 906 showed no differences .\nfurther analysis of the raw materials by liquid chromatography ( lc ) and mass spectrometry ( ms ) showed that , when compared with lot number 906 , lot number 002 had a separated peak on lc and an abnormal fragment peak on ms , suggesting the presence of impurities ( fig .\nall indigo carmine numbered as 001 and 002 were recalled and its usage was restricted .\nthe term anaphylaxis has been used for all types of acute life - threatening , generalized hypersensitivity reactions due to abnormal sensitivity to a triggering agent .\nalthough indigo carmine has no known activity in the human body , it has been found to directly activate alpha - adrenergic receptors , which may lead to reflex bradycardia and/or hypertension .\nhypotension after indigo carmine administration is an unexpected adverse effect and has been reported in fewer than 10 patients over 80 years of use .\nsudden , severe hypotension after indigo carmine administration was first reported in a series of four patients with no known drug allergies who underwent radical prostatectomy under epidural anesthesia . due to the temporal association between indigo carmine injection and the hemodynamic change ,\nusually , indigo carmine might cause both stimulant and depressant effects simultaneously , however , those cases could be induced by unopposed depressant component under sympathetic blockade .\nsevere hypotension , bronchospasm and urticaria after administration of indigo carmine were observed in a patient under general anesthesia .\nthat patient , who was undergoing transurethral resection of a bladder tumor , manifested the complete spectrum of anaphylaxis five minutes after injection of indigo carmine , including hemodynamic collapse , cutaneous changes , laryngeal edema and bronchospasm . due to a lack of prior allergies or prior exposure to indigo carmine\n, their case was thought to be caused by histamine release such as an anaphylactoid reaction .\nlife - threatening adverse reaction associated with indigo carmine presenting as even asystole was reported .\nsevere hypotension , bradycardia , hypoxia were observed after indigo carmine injection , and then the patient became asystolic .\nfollowing chest compression and intraaortic balloon pump support , the patient 's blood pressure was stabilized .\nthe patient 's cardiac arrest event was believed to be due to an anaphylactoid reaction in response to indigo carmine .\na diagnosis of anaphylaxis requires evidence of involvement of three or more organs and the detection of specific ige or a positive skin test to the alleged agent .\nhowever , since these reports did not verify these findings , it would be reasonable to diagnose these events as idiosyncratic reactions , including anaphylaxis . compared with the previous reports ,\nour patients had somewhat bizarre clinical manifestations . during the period described for all five patients , we used lot numbers 001 and 002 of indigo carmine on 15 patients .\nhypotensive episodes in some of the other patients may have been overlooked because their symptoms were mild and they recovered immediately . in all five patients described above , saline replacement was adequate and there was no massive blood loss .\nthere were no symptoms or signs suggesting anaphylactoid reactions , such as cutaneous changes or wheezing .\ntwo patients who experienced hypotensive episodes were tested for hypersensitivity to indigo carmine of lot number 002 by skin prick tests and intradermal skin tests , and both were negative . although a negative response to a suspected agent is unreliable in ruling out drug hypersensitivity , the clinical manifestations of these patients indicate that drug hypersensitivity or anaphylaxis was unlikely causes .\nwe focused on the five patients who experienced hypotension serially within a one month period , and suspected that flaws in production were responsible for these adverse reactions . during the manufacturing process\n, indigo carmine molecules may be fragmented by accelerated electron beams , and these fragmented ions can be classified by their mass to charge ( m / z ) ratios on ms ( fig .\nanalysis of the raw materials by lc / ms showed an abnormal peak in lot number 002 that was not present in lot number 906 .\nthis additional peak contained abnormal amounts of fragmented ions , with m / z = 340 , which had not been filtered out during the manufacturing process .\nraw materials , reagents , and degradation during manufacture and storage are all possible sources of impurities in drugs\n. these impure drugs may cause various adverse reactions , regardless of their pharmacological effects . determining the lot number of the drug may be helpful in investigating the causes of adverse reactions .\nusually , physicians tend to ignore or miss symptoms and signs if they are not critical .\nhowever , practitioners should always pay attention when using drugs and prevent further adverse drug reactions by meticulous monitoring and prompt reporting .", "answer": "indigo carmine has been used for eight decades with few adverse effects . \n several of our patients , however , experienced severe hypotensive episodes after indigo carmine administration within a period of one month . \n analysis of the raw materials used to formulate the preparation of indigo carmine we used showed that they contained impurities . \n following recall of these impure materials , none of our patients experienced further hypotensive episodes .", "id": 714} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nkienbck s disease , defined as avascular necrosis of the lunate , is a relatively rare condition with a poorly understood etiology .\nthe disease is a relatively rare condition in which the etiology and natural history of this condition are poorly understood and even more poorly documented in the literature .\na wide array of treatment recommendations is available , and reported results vary , which may hinder consistent treatment recommendations .\nconservative and invasive treatments for kienbck s disease include the following : wrist immobilization with a splint during early disease stages , surgical joint - leveling procedures to attempt to reduce loading on the joint and to promote revascularization and increased blood flow , vascularized bone grafting , proximal row carpectomy , and total wrist arthrodesis .\nproximal row carpectomy and total wrist arthrodesis attempt to alleviate arthritis pain due to carpal collapse ; however , these 2 interventions greatly limit range of motion .\nnone of these treatments effectively address the chronic pain , loss of range of motion , and decreased grip strength associated with kienbck s disease .\nthe staging distinguishes only the state of collapse in an ordinal classification scheme and does not allow localization or indicate partial involvement of the lunate , which the image contrast from mri may provide .\nosteochondral transfer for treatment of kienbck s disease may be possible for individuals with segmental or incomplete avascular necrosis of the lunate .\nprevious investigators have acknowledged the importance of donor site cartilage thickness to aid in minimizing postoperative abnormal stresses and resulting poor function .\nselection of donor cartilage with an appropriate thickness may be difficult due to source availability and donor site location relative to the load - bearing region of a joint , which may lead to donor site morbidity .\nan alternative to matching cartilage thickness is the matching of curvature of the articular surface . matching the curvature of donor and recipient sites\nhas been shown to maintain preoperative contact stresses for a given loading regimen . in this short communication , we report the treatment of a patient s kienbck s disease by combining mri with mathematical modeling to optimize the congruency between the curvature of donor and recipient sites of an autologous osteoarticular plug transfer .\nthe purpose of this study was to describe the feasibility of a novel surgical technique .\nthe results indicate that donor site selection for autologous osteoarticular transfer using a quantitative evaluation of articular surface curvature may be beneficial for optimizing the likelihood for restoring the radius of curvature and thus joint articulation following cartilage repair .\na 48-year - old , right hand dominant woman had left wrist pain associated with decreased wrist flexion since september 2009 . in november 2009 , the patient experienced severe wrist pain after falling on her hand . after acquiring standard radiographs ,\nthe woman was diagnosed with kienbck s disease , and a proximal row carpectomy was recommended by an initial orthopedic surgeon .\nthe patient sought a second opinion after understanding that the carpectomy would not only reduce pain during activities of daily living but would also limit range of motion . upon presentation to our institution ,\nphysical examination of the left wrist revealed no focal swelling , dystrophic changes , or evidence of muscular atrophy .\nthe left wrist range of motion was 20 of flexion and 30 of extension ; the patient had full , painless range of motion in her right wrist .\ngrip strength in her left hand was 111.2 n as compared with 333.6 n in her right hand .\nmri of the wrist was performed utilizing a clinical superconducting 3-t imaging unit ( sigma hdx , general electric healthcare , waukesha , wi ) and a dedicated wrist coil .\npulse sequencing included a 3-dimensional gradient - recalled sequence with tr / te of 39/14 milliseconds , field of view of 9 cm , slice thickness of 1 mm with no gap , flip angle of 10 , and band width of 41.7 khz .\ncoronal , sagittal , and axial cartilage sensitive fast spin echo sequences were obtained with a long tr ( 4,000 - 5,500 milliseconds ) , moderate te ( 31 - 38 milliseconds ) , field of view of 8 to 9 cm , slice thickness of 2 to 3 mm , acquisition matrix of 512 512 ( 320 - 352 ) , 2 excitations , a band width of 14.7 to 41.7 khz , and echo train length of 10 to 12 .\ncoronal fast inversion recovery sequence was performed with a tr of 5200 milliseconds , te of 23 milliseconds , inversion time of 170 milliseconds , field of view of 9 cm , slice thickness of 2.5 mm , matrix of 288 192 , 2 excitations , band width of 31.2 khz , and echo train length of 12 .\nthe examination demonstrated collapse of the proximal pole of the lunate , with subchondral sclerosis and a mild bone marrow edema pattern ( fig .\n1 ) . foci of completely devitalized marrow were noted in the proximal pole with an associated intense synovitis .\nmoderate partial wear of cartilage was seen over the collapsed lunate with preservation over the radial side of the lunate fossa .\na best - fit circle was manually placed on the lunate with its articulation with the distal radius to determine the joint curvature .\npreoperative coronal ( a ) and fat - suppressed ( b ) fast spin echo images of the wrist demonstrate sclerosis and partial collapse of the lunate ( arrows ) with hyperintensity in the adjacent cartilage .\none - year postoperative sagittal ( d ) and fat - suppressed ( e ) fast spin echo images and computerized tomographic evaluation ( f ) demonstrate partial bony incorporation expected for the time interval .\ncomputerized tomographic examination was performed utilizing axial acquisition with a slice resolution of 0.8 mm , subsequently reformatted into sagittal and coronal reformations .\nconcurrent computerized tomography was performed to quantify the extent of subchondral collapse , which measured up to 1 mm .\nmri of the left knee was subsequently acquired to provide a digital template for the planned osteochondral transplantation .\na 3-dimensional t1-weighted spoiled gradient echo data set with frequency - selective fat suppression was acquired for cartilage segmentation : tr of 13.6 milliseconds , te of 3.0 milliseconds , field of view of 16 cm , flip angle of 20 , slice thickness of 1.5 mm , matrix of 512 512 , receiver bandwidth of 41.7 khz , and 1.2 excitations .\nthe cartilage was segmented from the image data using custom - written semiautomated software ( general eelectric healthcare ) , with minimal manual editing performed as needed .\na 3-dimensional mesh representation of the segmented lateral condyle image data was constructed and smoothed for curvature calculations .\ncurvature calculations were performed on the 3-dimensional surface mesh using a custom - written matlab ( mathworks , natick , ma ) program .\n2a ) , and a best - fit paraboloid ( z(x , y ) = ax + bxy + cy ) was fit to each vertex and the surrounding 2-ring neighborhood ( fig .\n2b ) . the analytical solutions for maximum curvature ( max ) and minimum curvature ( min ) were determined from the best - fit paraboloid ( fig .\nthis process is repeated for each vertex on the 3-dimensional surface mesh to generate max and min maps .\nregions with large values of min display concavities on a surface , and regions with large values of max display convexities of a surface .\nthe model of a paraboloid was chosen due to the computational efficiency as well as the verified accuracy of the curvature calculation as compared to other numerical methods .\n( a ) each mesh vertex ( red point ) had a 2-ring neighborhood ( blue points ) calculated .\n( b ) the coefficients of a best - fit paraboloid through the vertex and 2-ring neighborhood were used to calculate the maximum and minimum curvatures .\nthe directions of maximum curvature ( red arrow ) and minimum curvature ( green arrow ) were also calculated .\n( c ) the direction and magnitude of the maximum curvature and minimum curvature at the vertex are shown by the orientation and radius of the pink and green circles , respectively .\nthe radius of each circle ( ) is the inverse of the calculated curvature ( = 1/ ) . at the indicated vertex ( red dot ) ,\nthe anterolateral femoral condyle had the maximum curvature in the mediolateral direction and minimum curvature in the anteroposterior direction .\nthe patient underwent osteochondral transfer from her left femoral condyle to her left lunate . using a tourniquet to control bleeding , the necrotic area of the lunate , which measured approximately 8 mm 1 mm 1 cm , was debrided .\nafter thorough debridement of the avascular necrotic bone , intraoperative fluoroscopy was used to identify and better assess the defect in the lunate . the donor site was filled with a synthetic acellular biphasic copolymer plug ( trufit , smith and nephew , andover , ma ) . using the digital template acquired from the algorithm ,\nan osteochondral plug from the left femoral condyle that closely matched the radius of curvature of the lunate , 12.7 mm from the manual measurement , was harvested during knee arthroscopy ( fig .\nthe location of the plug was assessed from the previously constructed 3-dimensional model of the articular surface , relative to the local anatomy . a 10 blade and rongeur\nwere used to fit the dimensions of the osteochondral plug with those of the lunate .\n2 fiberwire ( arthrex , naples , fl ) stitch was placed through the scapholunate ligament .\ninternal fixation was performed with a 1-mm drill , drilled antegrade through the lunate to fix the osteochondral plug ; a 1.5-mm 8-mm screw was then compressed across the plug with fixation in the distal aspect of the lunate .\nthere was no block in flexion , extension , or radial deviation , and the osteochondral fragment remained stable through a full range of motion .\nthe patient was placed in a sling and discharged with instructions to return for regular follow - up visits .\nmaximum ( left ) and minimum ( right ) principal curvature maps of the anterior portion of the lateral femoral condyle .\npostoperative radiographs demonstrated that the wrist was in good alignment and the hardware was intact .\nfollow - up radiographs and physical examinations were performed at 2 , 4 , 6 , 8 , and 10 weeks ; 3 , 4 , 7 , and 10 months ; and 1 year postoperatively .\nwe treated kienbck s disease with the aid of a 3-dimensional model of femoral articular surface and calculated the principal curvatures of the surface .\nthis was performed to determine the optimal congruency of the chondral donor and recipient sites .\nsurgical challenges for autologous osteoarticular transfer include restoration of the articular surface as well as the tidemark .\nkoh et al . have shown in a preclinical model that plugs left elevated or angled result in increased contact pressures , thus presenting potential risk to the cartilage on the opposite side of the joint . the mesh model created in the knee allowed for objective assessment of the articular surface to ensure more optimal plug alignment ,\nprovide reconstitution of joint architecture , and promote biologic incorporation of the plug into the recipient site .\nwe did not seek to evaluate the functional outcome of the surgical procedure in this short report but to introduce the feasibility of this novel surgical planning technique for osteochondral repair .\nthis case report presents the unique application of mri and mathematical modeling when applying the autologous osteoarticular transfer procedure to the lunate .\nthese techniques require only an additional limited 3-dimensional model of the knee with minimal scan time beyond the routine examination of the wrist for assessment of marrow viability and the integrity of the articular surfaces .\nadditional applications would include osteochondral lesions of the distal femur , capitellum , talus , and potentially , over the femoral head .\nfuture studies will refine the image acquisition and 3-dimensional modeling processes for optimal selection of the osteochondral plug based on local tissue morphology .", "answer": "kienbck s disease , defined as avascular necrosis of the lunate , is a relatively rare condition with a poorly understood etiology . \n conservative and invasive treatments for kienbck s disease exist , including wrist immobilization , surgical joint - leveling procedures , vascularized bone grafting , proximal row carpectomy , and total wrist arthrodesis . \n staging kienbck s disease using radiography assumes near complete avascularity of the lunate . \n the staging distinguishes only the state of collapse in an ordinal classification scheme and does not allow localization or indicate partial involvement of the lunate , which the image contrast from mri may provide . in this short communication , we report the treatment of a patient s kienbck s disease by combining mri with mathematical modeling to optimize the congruency between the curvature of donor and recipient sites of an autologous osteoarticular plug transfer . follow - up mri and radiographs at 1 year postoperatively demonstrated gradual graft incorporation and bone healing . \n the purpose of this study was to describe the feasibility of a novel surgical technique . \n the results indicate that donor site selection for autologous osteoarticular transfer using a quantitative evaluation of articular surface curvature may be beneficial for optimizing the likelihood for restoring the radius of curvature and thus joint articulation following cartilage repair .", "id": 715} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nThe AT-Hook motif as a versatile minor groove anchor for promoting DNA binding of transcription factor fragments\n\nPaper sections:\n\nTranscription Factors (TFs) are specialized proteins that, upon recognizing speci\ue103c DNA sequences, play a key role in the regulation of gene expression. 1 Therefore, alterations in their activity are at the origin of many diseases, including cancer. 2 Owing to this relevance, there is a great interest on the development of non-natural DNA binding peptides that can somewhat mimic the DNA binding properties of naturally occurring TFs. 3 It is well known that although the DNA-binding of TFs is mediated by relatively small peptide motifs, high-affinity DNA recognition requires the full protein domain and in many cases, the concerted action of multiple DNA-binding components. 4 Therefore, isolated monomeric DNA binding fragments of bZIP or zinc \ue103nger TF families do not interact with their target sites with signi\ue103cant affinity. We have previously shown that the DNA binding of these monomeric regions can be restored by conjugation to small molecule minor groove binders, such as distamycin or pentamidine derivatives. 5 Although these hybrids exhibit interesting recognition properties, they suffer from relatively poor sequence selectivity as a consequence of the intrinsic high affinity of the minor groove binders for A/T-rich DNA sites. 6 Furthermore, the synthesis of these conjugates requires elaborate multistep procedures, combining solution and solid-phase methods.
In the search for more efficient and selective bivalent DNA binders, we were intrigued by the AT-Hook motif, a naturally occurring cationic short peptide present in HMG-I(Y) eukaryotic nuclear proteins. 7 It is known that monomeric AT-Hooks bind their target sites with weak affinity (in the millimolar range). 7,8 However, these proteins attain high DNA-binding affinity thanks to the cooperative action of three appropriately spaced AT-Hook repeats. 9 NMR and crystallography studies have provided a detailed structural picture of the interaction of the AT-Hook (RKPRGRPKK) with DNA, and have shown that the central Arg-Gly-Arg core of this oligocationic peptide is deeply inserted into the minor groove (Fig. 1, le\ue09d), while the various lysines in the sequence (RKPRGRPKK) introduce additional electrostatic contacts with the phosphates of the DNA backbone. 10,11 The low intrinsic DNA affinity of monomeric AT-Hooks might discourage their application as minor groove anchors to promote the DNA binding of tethered TF fragments. However we envisioned that such low affinity might actually offer an opportunity for achieving greater sequence selectivity, because a high affinity, cooperative interaction should only occur in DNA sequences containing both targeting sites at adjacent positions (Fig. 1, right). Moreover, and importantly, the peptidic nature of the AT-Hook motif should considerably simplify the synthetic access to the conjugates.
Herein we report the design and synthesis of two peptide chimeras consisting of an AT-Hook motif linked to the DNA binding domains of GCN4 and GAGA, selected as representative members of the basic leucine zipper (bZIP) and Cys 2 His 2 zinc-\ue103nger (ZF) families of transcription factors, 1,12 and demonstrate that these conjugates exhibit excellent DNA binding affinity and selectivity for target speci\ue103c sites of 8-9 base pairs. The GCN4/AT-Hook conjugate (brH) was based on a GCN4 peptide fragment comprising of residues Asp 226 to Gln 248 , which has been identi\ue103ed as the shortest peptide that, as a disul\ue103de dimer, retains the speci\ue103c DNA binding properties of the full GCN4 DNA binding domain. 13 The design was based on the structures of the GCN4 dimer bound to the AP1 (5 0 -ATGA(c) TCAT-3 0 ) site, 14 and the third AT-Hook DNA binding domain of HMG-I(Y), RKPRGRPKK, bound to the PRDII sequence of the IFN-b promoter. 10 We built a qualitative computer model for the simultaneous interaction of both peptides bound to contiguous sequences of the DNA (see the ESI \u2020). Inspection of this model suggested that the Arg 245 residue in GCN4, which is oriented towards the adjacent minor groove, was a good candidate for introducing the tether between the two peptides (ESI \u2020). Thus, we synthesized the selected GCN4 basic region fragment containing the mutation Arg 245 / Lys following standard Fmoc/ tBu solid-phase peptide synthesis protocols (br, Scheme 1). 15 The Lys 245 residue was introduced with its side chain protected by an orthogonal alloc group, which could be selectively removed in the solid phase under Pd catalysis. Subsequent assembly of an O1Pen linker and the AT-Hook sequence, followed by standard deprotection/cleavage steps and reversephase HPLC puri\ue103cation, gave the expected peptide brH in a good overall yield (approx. 20%, Scheme 1). It should be remarked that the whole synthesis can be completed in one day.
Having at hand the desired peptidic chimera brH, we \ue103rst studied its DNA binding properties using standard non-denaturing EMSA experiments in polyacrylamide gels. 16 Thus, the incubation of the ds-oligonucleotide AP1 hs $AT, which contains a composite binding sequence including a AP1 half site (AP1 hs , TCAT) and an A/T-rich tract (AT, AATT), with increasing concentrations of brH led to a new, slow-migrating band, consistent with the formation of the desired brH/ AP1 hs $AT complex (Fig. 2a). Importantly, the conjugate brH does not elicit retarded bands when incubated with non-target sequences lacking the A/T-rich or the AP1 half site (Fig. 2b and c). This contrasts with previous conjugates with small molecule minor groove binders that also displayed considerable interactions with DNAs containing just A/T-rich sites, 5 and supports our premise that using low-affinity DNA minor groove binders leads to better selectivities.
In agreement with the results obtained by the EMSA, circular dichroism (CD) experiments revealed that the addition of 1 equiv. of the target oligonucleotide AP1 hs $AT to a 5 mM solution of brH promotes a signi\ue103cant increase in the intensity of the negative bands at 208 and 222 nm, which is consistent with the expected folding of the GCN4 basic region into an a-helix upon insertion in the major groove of the AP1 hs site (Fig. 2, bottom le\ue09d). 17 Fluorescence anisotropy titrations using the TMR-labeled dsDNA AP1 hs $AT con\ue103rmed that brH recognizes the DNA with a high affinity, with an apparent K D of z28 nM at 20 C (Fig. 2, bottom right), which is considerably better than the binding constants corresponding to each of the isolated components for 5 0 -CGCGTCATAATTGAGAGCGC-3 0 ; AP1 hs $GC: 5 0 -CGCGTCATCAGCGAGAGCGC-3 0 ; and GC$AT: 5 0 -GACGGAATTTGA-GAGCGTCG-3 0 . Bottom left: circular dichroism of a 5 mM solution (phosphate buffer pH 7.5) of brH (dashed line) and the same solution after the addition of 1 equiv. of the target AP1 hs $AT dsDNA (solid lane). The contribution of the DNA to the CD spectrum has been subtracted for clarity. Bottom right: fluorescence anisotropy titration of a 25 nM solution of TMR-AP1 hs $AT in the presence of increasing concentrations of brH. The best fit to a 1 : 1 binding model is also shown.
their respective targets (in the high micromolar-low millimolar range). Taken together, these results support the formation of a cooperative, bivalent DNA complex at speci\ue103c composite DNA sites of eight base pairs.
In order to con\ue103rm the general applicability of the AT-Hook motif as an effective minor groove DNA anchor for highly efficient and selective interactions, we designed a second chimera based on the DNA-binding domain of the GAGA protein: a monomeric Cys 2 His 2 zinc \ue103nger transcription factor. 18 As with GCN4, the design of the GAGA hybrid with the AT-Hook motif was based on the structure of the GAGA binding domain complexed with its target h3/h4 (GAGAG) DNA site. 18 Based on earlier reports that identi\ue103ed the minimal domain required for speci\ue103c binding, 19 as well as on our own previous work with GAGA-distamycin hybrids, 20 we selected a fragment of the DNA binding domain from residues Ser 28 to Phe 58 that by itself is incapable of interacting with its target DNA site. The selected peptide sequence was modi\ue103ed to include an appropriate mutation (Arg 44 / Lys) for tethering the AT-Hook to the abb core of the transcription factor (see the ESI \u2020). An inspection of the superimposed structures of the AT-Hook and the GAGA DNA binding domain bound to adjacent sites suggested that in this case the conjugate might be better assembled by a chemoselective ligation of fully deprotected peptides. In particular, we designed a synthetic scheme involving the coupling of a reactive bromoacetyl derivative of the AT-Hook with a nucleophilic cysteine attached to the side chain of the Lys 44 of the zinc \ue103nger moiety (Scheme 2). The chemoselective coupling to this thiol could be attained by blocking the other two natural cysteine residues (Cys 36 and Cys 39 ) by coordination to Zn(II) in the form of the folded zinc \ue103nger domain. 21 The core GAGA peptide containing a Lys 44 orthogonally protected with an alloc group in its side chain was synthesized following standard Fmoc SPPS procedures. The alloc group was removed under Pd catalysis, and a Cys residue was coupled to the side chain. Fmoc deprotection and acetylation, followed by standard deprotection and cleavage steps led to the expected peptide (SH)GAGA (Scheme 2). The AT-Hook sequence was assembled following standard methodology, and capped on its N-terminus with an electrophilic bromoacetyl handle (see the ESI \u2020). Finally, the nucleophilic peptide (SH)GAGA and the AT-Hook bromide derivative were coupled in solution in the presence of Zn(II). The reaction took place at rt in a deoxygenated phosphate buffer (pH 7.5) in the presence of 1.5 equiv. of ZnSO 4 . A\ue09der 1 h, HPLC-MS analysis showed the formation of the desired product, which was puri\ue103ed by HPLC and identi\ue103ed as the desired conjugate GAGAH (see Scheme 2 and the ESI \u2020).
As in the previous case, we assessed the DNA binding of the conjugate using EMSA under non-denaturing conditions. The incubation of a double stranded oligonucleotide containing the target composite binding site for the AT-Hook motif and the GAGA domain (AT$GAGA), at rt, with increasing concentrations of the conjugate GAGAH, led to the appearance of a new retarded band consistent with the formation of the expected peptide-DNA complex (Fig. 3a). Other oligonucleotides mutated in the GAGA or in the AT-Hook binding site failed to give rise to stable DNA peptide complexes, and indeed barely show the formation of any nonspeci\ue103c complexes (Fig. 3b and c, respectively). Moreover, \ue104uorescence anisotropy titrations using TMRlabeled dsDNA con\ue103rmed the high affinity interaction of the peptide chimera, with an apparent K D of 26 nM at 20 C (Fig. 3, Scheme 2 Strategy used for the synthesis of the AT-Hook/GAGA chimera GAGAH by the chemoselective modification of the GAGA Cys 2 His 2 peptide in solution. A limitation for the potential biological application of this type of DNA-binding peptide construct might derive from its presumable poor cell internalization. However, it is known that oligocationic peptides have a bene\ue103cial effect in cellular transport, 22 and therefore we decided to check whether the presence of the AT-Hook could enhance the cellular entrance of these conjugates. Thus, as a preliminary test, we incubated mammalian Vero cells with a tetramethylrhodamine (TMR) derivative of brH, as well as with a control peptide that lacks the AT-Hook (TMR-br, see the ESI \u2020). Remarkably, while TMR-br was essentially not internalized, 23 the incubation of the cells with TMR-brH led to a bright emission inside the cells, which was mainly localized in endosomes (Fig. 4). 24 Therefore it is clear that the presence of the AT-Hook enhances the transport across the cell membrane, which opens the door to the cellular applications of these peptide chimeras.
\n\nConclusions\nTaken together, these results demonstrate that the AT-Hook motif is a synthetically accessible minor groove binder that can be effectively exploited for the straightforward construction of functional DNA binding conjugates containing TF peptide fragments. The resulting bivalent chimeras display excellent DNA recognition properties in terms of affinity and selectivity, properties that rely on the cooperative action of two weakly DNA binding components. This work highlights the role of the hitherto overlooked AT-Hook motif as a DNA binding handle. The synthetic accessibility and nanomolar affinity and selectivity exhibited by these conjugates, together with their good cell transport properties, allows anticipation of potential applications to modulate gene transcription processes.
", "answer": "We report the development of chimeric DNA binding peptides comprising a DNA binding fragment of natural transcription factors (the basic region of a bZIP protein or a monomeric zinc finger module) and an AT-Hook peptide motif. The resulting peptide conjugates display high DNA affinity and excellent sequence selectivity. Furthermore, the AT-Hook motif also favors the cell internalization of the conjugates.", "id": 716} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndivided vascular lesions in the maxillofacial area into two groups : hemangioma and vascular malformations .\nthey are more common in women than men ( 3:1 ) . about 60% of hemangioma\nlips , tongue , and buccal mucosa are the most common sites of involvement . however , it is more likely to occur in the gingiva , mandible , palate , floor of the mouth , and parotid gland .\nthis report introduces a rare incidence of hemangioma in the buccal fat pad ( bfp ) along with phlebolithiasis .\nthe patient was a 28-year - old woman who referred with the chief complaint of a swelling and stiffness in the left cheek . from a clinical perspective\non palpation , a moving mass with a stiff area was felt ; and in intraoral examination , its position was felt in the anterior ramus .\nthe only point in the patient 's history was a course of laser therapy for skin rejuvenation in the left cheek and several other areas in her face . in the medical history of the lesion\n, there were 3 times of triamcinolone injection in the area during the last 3 years to treat the lesion by another physician .\nthe patient said that reduction in tumor size was seen for a while after these injections .\naspiration was performed for the patient through intraoral approach , whose result was negative . magnetic resonance imaging ( mri )\nmagnetic resonance imaging revealed a solid heterogeneous mass in the pterygopalatine fossa area with penetration and extension towards both buccal and masticator spaces on the left .\nthe submandibular area and carotid space were normal and no abnormality was seen in the nasopharynx area .\nmri revealed a solid heterogeneous mass in the pterygopalatine fossa area with penetration and extension toward both buccal and masticator spaces on the left .\n( b ) coronal view of t1 and t2 according to the results of clinical and radiographic examinations of the treatment plan , the excisional biopsy of the studied mass was selected under complete anesthesia . under general anesthesia ,\nthe patient underwent a surgery with intraoral access through a cut in the upper area of anterior ramus .\nafter dissection in the upper - side direction , vascular lesion was seen in buccal extension of the bfp [ figure 2 ] .\nthe bfp capsule was intact and the mass had offended no soft / hard adjacent tissue .\nthe possibility of a vascular lesion and second , for the purpose of liposuction for cosmetic goal and remove of the swelling on the patient 's cheek , the vascular mass was removed along with anterior lobe , as excisional biopsy through intraoral approach and hence that we did not enter into the vascular lesion [ figure 3 ] .\nthe clinical swelling of the cheek was removed immediately after the surgery . in the macroscopic viewpoint ,\nthe lesion was a yellow and dark purple mass measuring 2 cm 3 cm 4 cm along with a hard nodule - like area .\nmicroscopic results represented a vascular lesion composed of large amounts of small to large vascular structures covered with endothelial cells .\nview of the totally excised lesion showing hemangioma with phlebolith histopathologic view of the lesion showing vascular lesion composed of large amounts of small to large vascular structures covered with endothelial cells .\nhemangiomas usually appear within a few weeks after birth and have a growth rate that exceeds the growth rate of children . in this growth phase , hemangioma will have its own characteristics : endothelial cells getting fatter along with frequent mitotic division , increased number of mast cells , and multilayer basement membrane . following this stage ,\nflat and inactive endothelial cells are located in a context called fibrous fatty tissue with a normal view .\nsometimes , they can even involve all layers of the skin and offend the muscles . at the cellular level , hemangiomas are characterized by increased birth and death rate of endothelial cells and proliferation of mastocytes during the postnatal proliferative phase in the lesion .\nderived from young proliferating hemangiomas , capillary endothelium is easily grown in cell culture mediums and forms tubes . in accumulated hemangiomas ,\nhence , a normal hemangioma is an endothelial tumor with a very complex life cycle of cell proliferation and natural regression .\n. however , their clinical manifestations are not obvious sometimes until late infancy or even childhood .\nphleboliths consist of a mixture of calcium carbonate and calcium phosphate salts and are thought to form when a fibrous component attaches to a developing phlebolith and becomes calcified .\nradiologically , they have either a radiolucent or a radiopaque core , and repetition of this calcification causes an onion - like appearance or concentric rings .\nit should be noted that bfp is also a mass composed of fat tissue covered with a thin capsule membrane and is mainly located in the buccal space .\nbfp has a rich blood supply and it is a proven fact that bfp has multipotential cells .\nhowever , there was no report about the incidence of hemangioma in the bfp until 1956 .\ndeighan and barton first pointed to the incidence of a hemangioma case with phlebolithiasis in the bfp mass in 1956 .\nafter a review of english literature , only two cases of the incidence of hemangioma in the bfp mass were found , except the above case .\nikegami and nishijima reported the incidence of hemangioma in the bfp mass in a 23-year - old patient in 1984 . in that case , the tumor was enucleated and the presence of a cavernous hemangioma was confirmed .\nthe last report on the incidence of hemangioma in the bfp was published by tanaka et al . in 2000 .\nthe patient was a 3-year - old boy whose tumor was diagnosed 4 months after birth .\nunlike the report of ikegami and nishijima in which the lesion surface was irregular , in this case , the lesion surface was reported smooth . however , the surface of the removed lesion was also irregular in this report . like the case described in this report\n, no involvement was reported in the bfp mass adjacent areas in the previously reported cases .\nwhen radiographic examinations reveal a radiopaque lesion in the tumor , the differential diagnosis will be easier and there will be two possibilities : hemangioma or sialolithiasis of the parotid gland .\nhowever , when phlebolithiasis is not seen , preoperative diagnosis of hemangioma will be very difficult . in the report by tanaka et al .\n, the tumor was removed through extraoral access . however , in the extraoral access , the facial nerve is more likely to be damaged and risk of scar is present .\nhowever , tanaka et al . suggested that they used extraoral access because they assumed the probability of large extension of the lesion .\nthis shows the importance of careful radiographic examinations for accurate diagnosis of the lesion limits and the selection of appropriate surgical technique .\ntherefore , if the tumor does not have too large extension according to clinical and radiographic examinations , then intraoral access is preferred . in such cases\n, the use of only one single imaging modality can not provide enough information with the physician about the diagnosis and treatment of vascular lesions .\ntherefore , the use of mri and computed tomography ( ct ) is recommended in these cases .\nthe use of ultrasound / color doppler will also be very helpful for validating the mri and ct interpretational results .\nin general , the incidence of hemangioma in the bfp will be very rare , but in cases where this lesion is suspected , precise preoperative clinical and radiographic examinations are recommended .", "answer": "hemangiomas are benign vascular neoplasms characterized by an abnormal proliferation of blood vessels . \n buccal fat pad ( bfp ) is a rare place for hemangioma . in this report \n , clinical , radiographic , and histopathological findings are described in a rare case of hemangioma with phleboliths involving the bfp , and a review is made of the international literature on this subject .", "id": 717} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 56-year - old man was referred for biliopancreatic diversion with a duodenal switch ( bpd - ds ) for intractable complications associated with morbid obesity .\nhe had been unable to lose weight with orlistat 120 mg three times a day for three months .\nthe patient had diabetes mellitus for twenty years associated with hypertension , \" mal perforant \" and hepatic steatosis .\nhe had all features of the metabolic syndrome and was treated for sleep apnea with a nocturnal continuous positive airway pressure device ( c - pap ) .\nhis body mass index ( bmi ) at the time of the surgery was 48.7 kg / m , weighting 157.7 kg .\nthe patient 's blood tests showed normal electrolytes and a creatinine of 110 mol / l .\nthe glycated hemoglobin was 7.1% ( normal range 4.46.5% ) with fasting glucose values ranging from 7 to 11\nmmol / l with ldl - cholesterol and hdl - cholesterol levels of 2.63 and 0.99 mmol / l respectively .\nrest and exercise electrocardiograms were normal as well as a cardiac dobutamine stress echocardiography . a pseudonormalized pattern of left ventricular filling was present on a standard echocardiogram and a 24-hour holter was normal except for a slight decrease in heart rate variability . his medications before surgery consisted of metformin 850 mg tid ,\nrosiglitazone 8 mg daily , irbesartan 300 mg daily , diltiazem 120 mg daily , orlistat 120 mg tid and furosemide 20 mg every other day .\nhe was on insulin humalog tid ( 4246 u ) with insulin nph 90 u at bed time , for a total of > 200 u of insulin daily .\nhe underwent a modified scoparino 's biliopancreatic diversion with a duodenal switch [ 1 - 5 ] .\nthe patient had an hemodynamically stable pulmonary emboli on the day 12 after surgery and was anticoagulated .\nanthropometric measurements before and eleven months after the surgery are presented in the table 1 and figure 1 and metabolic improvements and echocardiographic findings are depicted in tables 2 and 3 respectively .\neleven months after the surgery , the medication consisted of metformin 850 mg tid , irbesartan 150 mg daily , 50 000 u of vitamin d2 , ferrous sulfate 300 mg daily , 25 000 u of vitamin a , calcium 500 mg and one tablet of vitamins and mineral supplements daily ( centrum forte ) .\nanthropometric variables before and after biliopancreatic bypass surgery anthropometric variables before and after biliopancreatic diversion surgery anthropometric measurements were assessed using a bioimpedance balance ( tanita tbf 350 ) metabolic profile before and after biliopancreatic diversion surgery blood pressure and echocardiographic variables before and after biliopancreatic diversion surgery bp : blood pressure ef : ejection fraction from\nobesity is associated with an increased risk of coronary artery disease ( cad ) and mortality [ 6 - 8 ] .\nmorbidity and mortality rates rise proportionally to the degree of obesity in men and women and the impact of excess body fat is more significant in younger subjects than older ones [ 9 - 12 ] . in a 10-year follow - up ,\nmen and women with a bmi 35.0 kg / mhad a relative increased risk of developing diabetes of ~23 and ~17 fold respectively compared to a control group with a bmi between 18.5 and 24.9 kg / m . independently of the bmi , the relative risk of developing diabetes mellitus increases with weight gain as shown in the nurse 's health study .\nmoreover , in that study , women who voluntary lost more than 5.0 kg reduced their risk of diabetes by 50% .\nweight loss also lowers blood pressure . in a 3-year follow - up of non - morbidly obese patients with a mean bmi of 31 kg / m\n, patients who maintained a 4.5 kg weight loss had a relative risk of hypertension of 0.35 or , a reduction of 0.45 mmhg in systolic blood pressure and 0.35 mmhg in diastolic pressure per kg of weight lost .\nin addition to higher cardiac output in obese patients , left ventricular volume and filling pressures are higher than normal .\nthis usually results in the development of left ventricular strain , which leads to hypertrophy , often of the eccentric type . left ventricular diastolic function is thus frequently impaired .\nweight loss has a beneficial impact on the functional and the structural cardiac status . in a study of obese patients with a mean bmi of 32.7 kg / m\n, weight loss of 8 kg over a period of 25 weeks was associated with a significant decrease in left ventricular mass .\nweight loss lowers oxygen consumption at any given work rate , decreases cardiac output and blood pressure while left ventricular filling pressures decreased as left ventricular stroke volume diminishes . in a study of obese patients with a bmi > 40\nkg / min whom surgical weight loss with vertical gastric banding ( vgb ) induced a decrease in body weight of 20% at six months , left ventricular wall thickness , particularly the septal and posterior walls , decreased .\nthe national institutes of health ( nih ) suggested that surgical therapy be proposed to those patients with a bmi level > 40 kg / mor > 35 kg / mwith serious medical conditions including hypertension and obstructive sleep apnea .\nsurgical intervention , when indicated , brings significant improvement such as a decrease in excess weight and comorbidities ; these include hypertension , diabetes , dyslipidemia [ 3,14,25 - 28 ] and sleep - related disorders .\none can expect a mean reduction of 60 to 75% of excess body weight with biliopancreatic diversion which can persist for 4 to 8 years after surgery [ 3 - 5,30,31 ] .\nthe duodenal switch operation , introduced by hess in 1988 , variant of the biliopancreatic diversion of scopinaro , helps in preserving normal eating habits , and the majority of patients undergoing the procedure will have normalization of glucose levels , triglyceride levels and blood pressure early weeks after the surgery [ 3 - 5 ] .\nindeed , in a review of 440 obese patients ( mean weight of 183 kg ) who underwent biliopancreatic diversion with duodenal switch , all of the 36 type 2 diabetic patients discontinued their medication over a 7-year follow - up period .\noperative mortality is between 0.5% and 2% and early complications include pulmonary embolus ( 0.5% ) and anastomotic leaks ( 12.5% ) .\nlate complications presents in the form of anemia , anastomotic ulcerations , bone demineralization , neurological complications and protein malabsorption ; all of which can be addressed with appropriate supplements . moreover , significant nutritional and metabolic complications may be less frequent than previously thought .\neleven months after the surgery , our patient had lost 40% of his body weight , and body fat mass was reduced by 41 % ( figure 1 ) .\nthe medication was greatly lightened while the patient maintained fasting glucose values ranging from 5 to 7 mmol / l and a blood pressure less than 130/80 mmhg ( table 2 ) .\nindeed , rosiglitazone was discontinued , the insulin that averaged > 200 u daily was no more necessary , diltiazem was discontinued and the dose of irbesartan was halved .\nthe 25% decreased in waist circumference is probably clinically significant albeit waist circumference may be less reliable in patients with a bmi > 35\nkg / m . finally , sleep apnea syndrome improved as the patient was no longer on c - pap .\nleft ventricle hypertrophy is recognized as a strong independent risk factor for cardiovascular morbidity and death and changes in cardiac structure following surgical weight loss have been observed . in the present case ,\nthe left ventricle mass index decreased by 15% and the thickness of the septal and posterior walls of the left ventricle were reduced ( table 3 ) .\nmoreover , using doppler mitral flow velocity with the e / a ratio , we demonstrated that left ventricular diastolic dysfunction actually improved . before the operation , the e / a ratio was higher than 1 with a significant decrease during the valsalva maneuver which corresponds to a pseudonormal ventricular filling or grade 2 filling pattern .\nafter the operation , the e / a ratio was smaller than 1 indicating a delayed relaxation of grade 1 filling pattern , representing an improvement in the diastolic function ( table 4 ) .\nmitral doppler at rest and during the valsalva maneuver before and after biliopancreatic diversion surgery e wave : early transmitral filling velocity a wave : transmitral atrial filling velocity e / a : early / atrial transmitral filling velocity this case report emphasizes the improvement in cardiovascular parameters , including the diastolic function ( demonstrated by a pseudonormal ventricular filling or grade 2 filling pattern ) and sleep apnea syndrome , following weight loss - induced by the biliopancreatic diversion with duodenal switch .\npp envisioned the paper and pw , pp prepared the initial draft of the article .\nbpd - ds : biliopancreatic diversion with a duodenal switch c - pap : continuous positive airway pressure device vgb : vertical gastric banding nih : national institutes of health e / a ratio : early / atrial transmitral filling velocity\nthe authors want to express their gratitude to suzie laroche , louise marois and claudette fortin for the quality of their intervention and the work on this particular population .", "answer": "backgroundsevere obesity is associated with important morbidity and increased mortality . \n the successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities . \n bariatric surgery , particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions.case presentationa 56-year - old man with severe clinical obesity underwent a biliopancreatic diversion with a duodenal switch after unsuccessful treatment with weight loss pharmacotherapy . \n he had diabetes , hypertension and sleep apnea syndrome and was on three medications for hypertension and two hypoglycemic agents in addition to > 200 insulin units daily . \n eleven months after the surgery , he had lost 40% of his body weight . \n the lipid profile showed great improvement and the hypertension and diabetes were more easily controlled with no more insulin needed . \n the pseudonormalized pattern of left ventricular diastolic function improved and ventricular walls showed decreased thickness.conclusionbiliopancreatic diversion may bring metabolic and cardiovascular benefits in severely obese patients from a cardiovascular perspective .", "id": 718} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 26-year - old female patient was transferred to the samsung medical center from an outside institution due to severe refractory cardiogenic shock .\nthe patient was diagnosed with non - hodgkin s lymphoma 2 years prior and underwent 6 cycles of chemotherapy , which included doxorubicin .\nafter chemotherapy treatments were completed , the patient suffered from orthopnea and dyspnea , and an echocardiography revealed a severely depressed left ventricular ( lv ) ejection fraction ( 25% ) and dilated lv . due to complications from cancer treatments , she had an episode of acute decompensated heart failure and was referred to samsung medical center . on initial presentation ,\nvital signs included arterial blood pressure of 79/27 mmhg , heart rate of 133 beats / min , respiratory rate of 28 breaths / min , and body temperature of 35.9c .\nshe had pulmonary edema with bilateral pulmonary congestion ( fig . 1 ) and multiorgan failure with liver and kidney involvement . despite the use of inotropes and vasopressors , we were unable to achieve stable vital signs .\npercutaneous extracorporeal life support ( p - ecls ) was then placed using the left femoral artery and vein .\nhowever , the left leg became ischemic after several hours , and we decided to shift the cannulas to the right groin .\nthe patient was brought to a hybrid operating room , and the groin was opened bilaterally .\nthen , the arterial and venous cannulas were inserted through the common femoral artery and vein , and the catheter for the superficial femoral artery was inserted at the same time . the following day ,\ntransthoracic echocardiography revealed a distended left ventricle , and the chest x - ray showed worsening pulmonary edema . in this case , we determined that an atrial septostomy was not a viable option since both the femoral veins were already cannulated or had been surgically repaired .\ninstead , we performed an emergency standard median sternotomy and inserted a vent catheter ( malleable 20 fr . ) with a tip - cut into the right upper pulmonary vein and passed it into the left ventricle .\nthen , the inserted vent catheter was connected to the venous line of the p - ecls circuit via a y - shaped connector ( fig .\n, the pump flow was maintained at 2.4 l / min / m , obtaining a mean systemic pressure of 60 mmhg and central venous pressure of 8 mmhg .\nthe flow through the vent catheter was measured to be 1 to 2 l / min .\nthe patient was on p - ecls and left heart venting for 5 days . during this time ,\n3 ) . transthoracic echocardiography revealed improved right and lv function and decreased chamber size .\nwhen the function of the right heart and the lung improved , the drainage from the femoral vein was gradually reduced by progressively clamping the venous line and lowering the r.p.m . in this way , the system was modified from p - ecls to paracorporeal lv assist device ( lvad ) by the complete clamping of the femoral venous drainage catheter .\nthus , the femoral venous cannula and the oxygenator were removed on postoperative day 5 .\nthe reasons for our decision were complete lv support , possible longer - term support due to the absence of the oxygenator and the low level of anticoagulation , and the prevention of recurrent lv distension . on postoperative day 8 , we were able to wean the patient from lvad and remove all cannulas from her chest and groin .\nshe was extubated and was finally discharged home on hospital day 28 . during follow - up ,\nthe lv ejection fraction worsened from 40% to 20% , and the symptoms of dyspnea became worse than before hospital discharge .\ncurrently , this patient is on the heart transplant list and is waiting for transplantation .\nhowever , due to its inability to directly drain the left heart , its effectiveness in assisting the heart is limited .\nadditionally , several factors including severely reduced lv function , blood from native pulmonary and bronchial circulation , and increased afterload due to retrograde perfusion from the arterial cannula may lead to lv distension .\nthis resultant lv distension can cause pulmonary edema , pulmonary hemorrhage , and myocardial ischemia .\nalthough paracorporeal lvad placed through a median sternotomy provide better hemodynamic support without the risk of lv distension , complications of central cannulation such as bleeding and infection limit the widespread use of this technique .\nwe report a case in which trans - sternal lv drainage was utilized while the patient was receiving p - ecls that was followed by a subsequent switch to paracorporeal lvad without further surgery .\nthis strategy allowed the transformation of peripheral circulatory support into effective myocardial and systemic circulatory assistance and minimized the surgical risk .\nalthough p - ecls offers excellent support to the blood circulation , its effect on the heart is less favorable .\nthe left atrium can receive blood from the right heart and bronchial circulation . in the case of severe lv dysfunction\n, the lv can not eject the received blood to overcome the increased afterload due to the retrograde p - ecls flow .\nthe consequences of lv distension include pulmonary edema , pulmonary hemorrhage , right ventricular distension , and increased intraventricular pressure , which can lead to myocardial hypoperfusion and ischemia .\nthe effect of p - ecls on lv distension was investigated previously by some authors . in an animal model of acute heart failure ,\nkawashima et al . reported that the resolution of ventricular fibrillation was related to lv unloading and reduction in myocardial oxygen consumption .\nmyocardial perfusion is proportional to the decrease in the lv wall tension and the compression of intra - myocardial coronary vessels .\ntherefore , lv decompression favorably affects ventricular recovery and increases the possibility of weaning from p - ecls . for this reason , a careful evaluation of the status of the lv and prompt drainage in the case of a pressure increase\nthere are several techniques to decompress the lv , including a percutaneous trans - septal left atrial approach , lv venting through the right upper pulmonary vein , and direct lv apex cannulation . although percutaneous lv venting does not require a surgical incision , the effectiveness of lv decompression can be limited according to the degree of mitral regurgitation . thus , surgical venting is a more favorable option than percutaneous septostomy .\nreported minimally invasive lv drainage in which an apical cannula is inserted into the lv apex transcutaneously .\nalthough direct drainage of the lv through a trans - sternal approach is technically more complex , it has the advantage of high efficacy with respect to the intraventricular dynamics .\nfurther , our group was more familiar with the trans - sternal approach at that time .\nmanagement after an lv venting procedure is still controversial , particularly since there is uncertainty in terms of patient stability after weaning from p - ecls .\nthere are three ways of weaning from venoarterial ecls , namely the one - stage removal of all ecls cannulae , vent catheter removal and subsequent venoarterial ecls weaning , and venous cannula removal and subsequent paracorporeal lvad weaning . in this case\n, we decided to shift to paracorporeal lvad from p - ecls by progressively clamping the venous line and lowering the flow to the oxygenator until complete exclusion from the circuit .\nthis allows for a heparin- and oxygenator - free trial of extracorporeal circulation , which reduces the chances of bleeding or thromboembolism .\nthe low risk of bleeding and thromboembolism allows longer - term support for heart transplant than venoarterial ecls\n. the other advantages of our strategy include prevention of recurrent lv distension and pulmonary edema . in summary ,\np - ecls offers excellent circulatory support in emergency settings and assures rapid and systemic perfusion .\nhowever , p - ecls can negatively affect lv physiology and can potentially jeopardize myocardial recovery .\nthus , a careful evaluation of the lv status and prompt drainage in the case of pressure increases should be considered .\nour strategy assures complete lv venting and allows for a simple conversion of p - ecls to paracorporeal lvad .", "answer": "percutaneous extracorporeal life support ( p - ecls ) is a useful modality for the management of refractory cardiac or pulmonary failure . \n however , venoarterial p - ecls may result in a complication of left ventricular distension . in this case report \n , we discuss a patient with drug - induced dilated cardiomyopathy managed with venoarterial p - ecls and a left atrial vent catheter . \n the venoarterial p - ecls was modified to a paracorporeal left ventricular assist device ( lvad ) by removing the femoral venous cannula . \n after 28 days of hospitalization , the patient was successfully weaned from the paracorporeal lvad and discharged home from the hospital .", "id": 719} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe sizing of pda for device implantation is based on the automatic calculations of dimension by the inbuilt sizing software in the cardiac catheterisation laboratory and many experienced interventionists believe their eyeball measurements more .\nthe estimations can be erroneous if the calibrations are not proper , leading to catastrophic embolisation of the device , needing emergency surgical removal as was needed in our patient .\ncalibration by comparing with the fluoroscopic images of measured metallic sizing devices placed outside body can be misleading because of magnification errors.1 in order to circumvent these problems we suggest some novel ways which take care of magnification errors and avoid the need for aortic root angiography .\nan eight year child with echocardiographically documented 6 mm patent ductus arteriosus ( pda ) was planned for device closure .\nfemoral venous access was obtained using 8f sidearm sheath and the artery cannulated with a 6f sidearm sheath .\na 6f pigtail catheter was advanced through the femoral arterial sheath into the descending aorta at the mouth of the pda and an angiogram obtained in a lateral projection delineating the ductus ( figure 1 ) .\nthe minimum diameter at the aortic end was 6 mm and a 8 - 10 mm pda device was selected for deployment .\na 7f swan - ganz catheter was advanced into the the pulmonary artery through venous route and a 0.35 \" terumo wire advanced through the pda into the descending aorta .the terumo wire was exchanged with an 0.35 \" extra stiff amplatzer wire and the swan - ganz catheter with the pda delivery system . an 8 - 10 mm size pda device was released across the ductus and after confirming the proper position by repeat angiogram which showed a small residual shunt flow which may be expected .\nangiogram in lateral plane showing a small residual left to right shunt with pda device in place before unscrewing of the stylet after a short while , the device suddenly embolised into the left pulmonary artery ( figure 2 ) .\nthe patient had a brief episode of mild hypotension which improved spontaneously and his oxygen saturations remained static .\nan attempt was made to retrieve the device percutaneously by a snare and later by a bioptome but the trial was given up as the device tended to go more distally , in which case even surgical removal would be difficult .\nthe patient was discussed with the cardiac surgeon who shifted the patient for emergency surgery .\nafter considerable debate surgeon decided for a left thoracotomy hoping to avoid cardiopulmonary bypass and closed the ductus . later the left pulmonary artery was separated from the surrounding tissues and umbilical tape passed around it proximally for control of bleeding . a 1.5 cm longitudinal incision was made distal to the umbilical tape which was kept under traction and a long curved forceps passed toward the pulmonary hilum and the device retrieved .\ncine image in lateral plane showing device embolized into left pulmonary artery soon after its release from stylet . showing the pda device being retrieved from left pulmonary artery via left thoracotomy without cardiopulmonary bypass . in order to prevent such eventualities we tried to devise some alternative ways of sizing a pda .the\nfirst involves measuring a fully inflated tyshak pulmonary balloon outside the human body with a caliper and then inflating the balloon to the same pressure in the right ventricular outflow tract passed over a 0.35 \" extra - stiff wire , and repeating the measurements , and using the same calibration factor for sizing of pda visualized by aortic arch angiogram .\npreviously , some radio opaque sizing devices have been used placing them outside human body which can have magnification errors if not placed exactly at the level of heart.2 the second method involves advancing a tyshak balloon 2 - 4 mm bigger than the echocardiographic dimension across the pda and inflating the balloon with dilute dye under low pressure without dilating the ductus so that it forms an impression of the ductus which is recorded in a cine mode in multiple planes , and the plane delineating the exact anatomy of the ductus is used for measurements after proper calibrations as mentioned above without the need for aortic arch angiogram ( figures 4 and 5 ) . showing measurement of diameter of inflated tyshak balloon by a caliper after inflating it with fixed quantity of contrast .\nangiogram in lateral plane showing an inflated tyshak balloon across the pda making an impression of the ductus .\ntechnological advances have made nonsurgical closure of the pda a simple and a routine percutaneous intervention .\nthe use of the amplatzer device occluder ( ado ) has further simplified the method and improved the results with minimal complications .\nhowever there are situations where complications are encountered and surgical help is required to ameliorate them .\nfaella and colleagues reported 15 procedure related complications in 316 patients which included hemolysis , left pulmonary artery artery stenosis , device protrusion into aorta causing coarctation , device misplacement and one death following device embolisation.2 late embolisation of the device to the left pulmonary artery has been reported with impaired left pulmonary perfusion six months after implantation requiring surgical removal .\nm vavuranakis et al reported severe hemolysis with jaundice , anemia and hemogloginura on the second day following deployment of smaller sized coil due to improper sizing which needed removal and replacement by an ado after repeat sizing using balloon tipped catheter.3 the complications can be reduced by proper expertise and optimal sizing of the ductus .\nsizing of atrial septal defect ( asd ) by inflating a balloon across the asd till a circumferential waist is created and measuring the waist ( stretched balloon diameter ) and also inflating the balloon outside by same amount of dye across sized rings , is a standard method.45 using a similar method for the pda is not routine since angiographic visualization is usually adequate .\nhowever making an impression of the ductus by inflating a balloon across it can give a detailed anatomy about the length and breadth of the ductus in multiple planes without the need for multiple dye injection and may help in the selection of proper sized device .", "answer": "nonsurgical closure of patent ductus arteriosus ( pda ) using a duct occluder placed percutaneously is currently the first line of therapy and the success rate is quite high . \n several devices are currently available . \n an eight year child underwent device closure of the ductus . \n however after deployment of the device it , became dislodged into the left pulmonary artery . \n several attempts at catheter retrieval failed . \n the child underwent successful surgical removal of the device without cardiopulmonary bypass .", "id": 720} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary mesenchymal tumors of the intestinal tract are a heterogeneous group of tumors with a wide clinical spectrum ranging from benign incidentally detected nodules to frank malignant tumors . traditionally the majority of these tumors were thought to be derived from smooth muscle cells .\nit has now been realized that the majority of these tumors are not smooth muscle or nerve sheath tumors , but represent a distinct clinico - pathological entity termed as gastrointestinal stromal tumor ( gist ) .\nit is currently believed that gist is a specific mesenchymal neoplasm and the term is used to refer to those mesenchymal neoplasms of the gastrointestinal tract ( git ) which express cd117 , a c - kit proto - oncogene protein , and show gain of function mutation of c - kit gene that encodes a growth factor receptor with tyrosine kinase activity .\nthe introduction of a new targeted treatment for gist in the form of imatinib mesylate , a receptor tyrosine kinase inhibitor , has further validated this entity .\ngist can occur at all levels of git and may also arise in extra - gi locations , principally mesentery , omentum and retroperitoneum and occasionally in pancreas .\napproximately 50 - 60% of gists arise in the stomach , 20 - 30% in small bowel , 10% in large bowel and 5% in esophagus .\nabout 30% of gist are malignant and liver is the most common site for metastasis.[710 ] the criteria for differentiation of benign from malignant gist remain controversial .\nmany parameters have been proposed , tumor size and proliferative activity have been found to be the most important prognostic indicators .\ngist reported outside the git t as apparent primary tumors are designated as extra - gastrointestinal stromal tumor ( egist).[1214 ] the frequency of egist is only 5 - 7% .\nbecause of overlapping morphology , gists are cytologically difficult to distinguish from other gastrointestinal mesenchymal neoplasms including smooth muscle tumors and nerve sheath tumors.[1519 ] although many investigators have described various features used in the cytologic diagnosis of gist , few have reported their findings in patients with malignant gist .\nthe present study is the largest series discussing the cytology of gists and egist from different anatomic sites including extremely rare sites like subcutaneous nodules , fluid cytology samples and metastasis from a primary pancreatic egist . in the present study we studied the cytomorphological features in 33 gist / egist from 27 patients .\nall patients of histologically and immunohistochemically confirmed gist and egist who underwent cytological examination over a period of ten years ( jan 2000-july 2010 ) were retrieved from the records of the department of pathology .\n33 specimens from 27 patients including 26 gist ( 13 primary , 12 metastatic , one recurrent ) and seven egist ( 5 primary , 1 metastatic , 1 recurrent ) were identified .\nthese included guided ( 28 ) and unguided ( 2 ) fine - needle aspirates , imprint smear ( 1 ) and fluid cytology ( 2 ) .\nfine needle aspiration cytology ( fnac ) was performed using 22 gauge needle attached to 10 ml disposable syringe under ultrasound guidance of intra - abdominal tumors .\nfna material was smeared on glass slides and slides fixed in 95% alcohol were stained with papanicolaou and hematoxylin and eosin stain while air dried smears were stained with may - grnwald - giemsa stain ( mgg ) .\nhistological categorization of gist of different sites into various risk groups was done as suggested recently by miettinen et al .\ncytology was reviewed in all cases with emphasis on the following cytological features : overall cellularity , smear pattern ( cohesion vs. dispersed cells ) , palisading , crush artefact , prominent vascular pattern , spindle versus epithelioid cell morphology , nuclear grooves and inclusions , nuclear pleomorphism , presence of nucleoli , round or blunt - ended oval or wavy nuclei , multinucleation / bizarre cells / or giant cells , perinuclear vacuoles , cytoplasmic quality , mitoses and necrosis .\nthe patients included 20 males and 7 females with male : female ratio of 2.67:1 .\nthe mean age was 50.6 years ( range : 26 - 76 , median : 52 years ) .\nthere were 18 primary tumours ( 5 gastric , 5 duodenum , 1 ileum , 1 ileocecal , 1 rectum , 4 intra - abdominal / retroperitoneal tumours , 1 mesentery ) , 9 hepatic metastases ( 5 gastric , 2 duodenum , 1 jejunum , 1 small bowel primary tumours ) , 1 ascitic fluid metastases ( gastric primary ) , 1 pleural fluid metastases ( jejunum primary ) , 1 subcutaneous nodule metastases ( gastric primary ) , 1 lump at base of penis ( rectum primary ) and 2 recurrences ( 1 ileum , 1 intra - abdominal / retroperitoneal ) . the smears were variably cellular .\nmalignant and metastatic lesions were commonly highly cellular . in patients with predominantly spindle cells on cytology (\nn = 18 ) smears showed cells often arranged in cohesive to loose three dimensional clusters and singly scattered or dispersed cells [ figure 1a and b ] .\nthe tumor cells often formed fascicles with parallel , side - by - side arrangements of nuclei . in these fascicles tumor cells\nthe stroma of the cohesive sheets present between the nuclei was loosely fibrillary and stained pink to magenta on mgg [ figure 1d ] .\nskenoid fibres were noted in a smear from liver metastasis of a patient with primary jejunal gist .\nspindle cells with high cellularity , closely packed to loose clusters and dyscohesive cells ( mgg , 100 ) ;\n( a ) spindle cells displaying elongated to wavy nuclei with blunt to tapered ends ( mgg , 200 ) ; ( b ) fascicles with parallel , side - by - side arrangements of nuclei with scant cytoplasm .\nnuclear palisading is also observed ( mgg , 100 ) ; ( c ) abundant extracellular stromal material ( mgg , 200 ) ; ( d ) ( inset : spindle cells with bipolar cytoplasmic processes ( mgg , 400 ) focal to diffuse epithelioid cell morphology admixed with spindle cells were observed in twelve samples and 3 tumors had only epithelioid cell type [ figure 2a ] .\nplasmacytoid appearance was noted in eight samples [ figure 2c ] few demonstrated rossetting and acinar structure arrangement reminiscent of adenocarcinoma [ figure 2d ] .\nthe nucleoli were indistinct in low grade tumors and prominent or multiple nucleoli were seen in high grade tumors irrelevant of cell type .\nthe presence of marked cytologic atypia with presence of bizarre and giant cells was identified in 6 tumors .\noccasional tumors displayed bubbly appearance due to multiple cytoplasmic vacuoles . in 9 cases mitotic figures were observed .\nthe pleural and ascitic fluid cytology smears exhibited loosely formed aggregates with epithelioid cell morphology .\nsmear showing groups of epithelioid tumors cells with round nuclei ( mgg , 200 ) ; ( a ) multinucleation ( mgg , 400 ) ; ( b ) plasmacytoid tumor cells displaying eccentric round nuclei with smooth nuclear membrane and fine chromatin ( mgg , 400 ) ; ( c ) acinar arrangement of tumor cells mimicking epithelial tumor ( mgg , 400 ) ; ( d ) ( inset : mitotic figure in a mixed gist ( mgg , 400 ) histology sections of all primary gist and egist were reviewed .\nthe majority ( n = 18 , 66.67% ) of tumors were classified as spindle cell type , while 3 ( 11.12% ) were classified as epithelioid type and 6 ( 22.23% ) as mixed cell type .\nthe cellularity of the majority of tumors was subjectively assessed as moderate ( n = 17 ) .\ncategorization of gist of different sites into various risk groups was performed as suggested recently by miettinen et al .\nthere was only one low grade tumor , 4 tumors with moderate risk , and 22 tumors were categorized as high risk .\nimmunohistochemically all tumors were positive for cd117 with strong intensity of positivity in the majority of tumors .\nthe cytological studies on gist in literature are not comparable as many of the earlier published cytologic studies have combined gist into a group of neoplasms encompassing leiomyoma , schwannoma , leiomyosarcoma , and an epithelioid leiomyoblastoma.[1517 ] however recently , few authors have established fnac as a reliable method for diagnosing gist and egist before surgical procedure [ table 1].[1830 ] we observed several morphologic features suggestive of high grade gist and egist . in recurrent , metastatic and malignant gist\nhowever , it was difficult to find mitoses in the cytologic smears because most of the tumor cells occurred in closely packed cohesive thick tissue fragments .\nli et al . , found that mitoses in the resected malignant gists were seldom seen in fnac smear .\nwe also found that malignant gists sometimes had no significant pleomorphism in the cytologic smears .\nnuclear inclusions were more commonly seen in malignant and metastatic tumors irrespective of cell type in our cases .\ndirty or necrotic background again was least reliable indicator of malignancy as it was seen in two samples only .\nwe agree with earlier descriptions that fna findings alone can not reliably assess behavior of gist .\nprediction of behavior by cytological features is likely to result in either underestimation or overestimation of malignant potential.[1825 ] summary of various series of gist and egist cytology cases described in the literature the differential diagnosis between gists and gastrointestinal leiomyomas is difficult owing to their overlapping clinical and cytologic features .\nleiomyoma shows varying cellularity and are composed of bland spindle cells with abundant cytoplasm often having a fibrillary appearance .\nleiomyosarcomas shows three - dimensional , tightly cohesive , sharply marginated syncytia of spindle cells , often with nuclear crush artefact .\nbenign and malignant nerve sheath tumors show fibrillar cytoplasm and wavy nuclei , similar to a subset of and characteristic features of nerve sheath differentiation , such as nuclear palisading , may be focal .\nepithelioid gists may cause significant diagnostic confusion with carcinomas , neuroendocrine tumors , and melanoma , particularly when metastatic and even hepatocellular carcinoma .\nthe regular round nuclei , with finely granular chromatin seen in many of cases raised the possibility of neuroendocrine tumor .\nkey features of melanoma are loose aggregates or isolated cells , cellular pleomorphism , enlarged nuclei with macronucleoli , binucleation , multinucleation and intracytoplasmic melanin .\nintranuclear inclusions , intracytoplasmic bile pigment and no bile duct epithelium are important distinguishing features .\nthe separation of metastatic gist from other metastasis is important since these may respond to imatinib . to conclude ,\nfirstly cytology is a useful method for preoperative diagnosis and follow - up of gists and egist .\ngist show a broad morphologic spectrum on cytology and gist should be considered as a differential diagnosis of tumors with spindle or epithelioid morphology . in an appropriate clinical and radiologic setting the presence of closely packed spindle or oval cells forming fascicles with parallel side - by - side arrangements of nuclei suggests gist .\nthe diagnosis of gist should also be considered in aspirates of the gastrointestinal tract , liver , mesentery , or abdominal wall mass lesions when epithelioid cells are the predominant cell type .\nthe presence of cellular dyscohesion , nuclear pleomorphism , necrosis and mitosis suggest malignant behavior , however absence of these features on cytology is not diagnostic of low risk benign behavior .", "answer": "background : the term gastrointestinal stromal tumors ( gist ) is used to refer to those mesenchymal neoplasms of the gastrointestinal tract ( git ) which express cd117 , a c - kit proto - oncogene protein.aims:to study the cytological features of gist and extra - gastrointestinal stromal tumors ( egist ) , to correlate them with histology and to determine cytological indicators of malignancy.materials and methods : cytological smears from patients diagnosed as gist / egist on histology were retrieved . from jan 2000 to july 2010 , 26 gist ( 13 primary , 12 metastatic , one recurrent ) and seven egist ( 5 primary , one metastatic , one recurrent ) cytologic samples from 27 patients were identified.results:the patients included 20 males and 7 females with a mean age of 50.6 years . \n tumor sites included stomach ( 5 ) , duodenum ( 5 ) , ileum ( 2 ) , ileocecal ( 1 ) , rectum ( 1 ) , liver ( 9 ) , retroperitoneum ( 5 ) , mesentery ( 1 ) , subcutaneous nodule ( 1 ) , supra - penile lump ( 1 ) , ascitic ( 1 ) and pleural fluids ( 1 ) . \n the smears were cellular with cohesive to loosely cohesive thinly spread irregularly outlined cell clusters held together by thin calibre vessels . \n the tumor cells were mild to moderately pleomorphic , spindle to epithelioid with variable chromatin pattern and variable cytoplasm . \n cellular dyscohesion , nuclear pleomorphism , intranuclear pseudoinclusions , prominent nucleoli , mitosis and necrosis were more prominent in malignant , metastatic and recurrent tumors.conclusions:gists show a wide spectrum of cytological features and the presence of mitosis , necrosis and nuclear pleomorphism can help in prediction of malignant behavior . \n further , cytology is a very useful screening modality in patients of gist and egist to detect early recurrence and metastasis at follow - up .", "id": 721} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a recent issue of the new england journal of medicine , greet van den berghe and co - workers published a confirmation of the life - saving effects of tight glycaemia control by intensive insulin therapy ( iit ) in medical intensive care unit ( icu ) patients .\nthis second study intended to answer some of the questions and criticisms raised by the landmark leuven study of 2001 , which reported a 4% decrease in mortality in a surgical icu population [ 2 - 7 ] .\nhopefully , these questions will be answered by the multi - centre assessments of the effects of iit , the nice - sugar and glucontrol trials , currently underway in australia and europe , respectively . before the completion of these two indispensable studies ,\ngreet van den berghe and colleagues wanted to confirm the life - saving effects of iit in medical icu patients in order to answer specific criticisms related to the type of patients , mostly surgical with two - thirds being post - cardiac surgery patients , in the first leuven study .\nindeed , patients with myocardial ischaemia could particularly benefit from a combination of a high amount of glucose and insulin , as reviewed recently .\ninterestingly , krinsley reported a similar reduction in mortality in a mixed population of medical and surgical icu patients .\ngreet van den berghe and colleagues succeeded but , as in most major contributions , their study raised more questions , which further argue for the importance of multi - centre trials .\n, this study can not be considered to be positive , as the long - stayers in whom a survival benefit was found were actually not randomised . the sample of long - stayer patients ( n = 767 ) was smaller than the calculated sample size of 1,200 patients that was required to test the working hypothesis ( a 7% reduction of the absolute risk of death ) with an alpha level of less than 0.05 and a beta level of 0.2 . in the entire set of patients , the intent - to - treat analysis indicated that there was actually no benefit related to iit .\nmoreover , mortality in the patients in whom the stay was shorter than anticipated ( less than 3 days ) was higher in the iit group ( 26.8% ; 56/209 ) than in the conventional treatment group ( 18.8% ; 42/224 ) .\nthis increase was found to be significant when analysed by the chi square test , but not by uncorrected proportional - hazards analysis , even after correcting for the difference in baseline risk factors .\ncompared to the first leuven study , some of the recorded secondary end points that could be considered as surrogate markers of severity ( icu and 28-day mortality , requirement for dialysis , incidence of bacteraemia , requirement for prolonged antibiotic therapy , incidence of hyperbilirubinaemia and ' hyper - inflammation ' ) were not influenced as hospital mortality was .\nother local factors could also have influenced the results , thereby questioning the applicability of the findings to patients managed in other icus .\nthe mean amount of parenteral glucose infused ( a mean of more than 220 g / day in long - stayers ) was probably higher than in most other icus , and parenteral steroids were used in more than half of the patients .\nunequivocally , these two factors reduce the risk of hypoglycaemia and the duration of episodes of hypoglycaemia , a major side effect of iit . nonetheless , the risk of hypoglycaemia was substantial , with 25.1% of the patients in the iit group experiencing a blood glucose level below 2.2\nmmol / l ( 40 mg / dl ) at least once , compared to only 3.9% in the conventional group .\nthe safety monitoring board of the german multi - centre study visep considered a similar increase in the incidence of hypoglycaemia important enough to stop this trial .\nclearly , the safety of iit needs to be assessed in patients with significant risk of hypoglycaemia .\nthe target ranges of glycaemia were 4.4 to 6.1 mmol / l ( 80 to 110 mg / dl ) and 10 to 11 mmol / l ( 180 to 200 mg / dl ) , implying that there was no assessment of an intermediary blood glucose value , which is often used .\ngreet van den berghe and colleagues already answered this question by analysing the data of the first study and concluded that there was a dose - response effect , with the largest improvement found in patients with the lowest blood glucose level .\nthis hypothesis was found retrospectively , however , and clearly requires confirmation from prospective trials .\nthe use of iit in leuven is probably easier than in other institutions with a lower nurse - to - patient ratio . for an iit approach ,\nlastly , insulin exerts many effects other than a decrease in blood glucose , which could possibly be beneficial or deleterious in different subsets of patients ; these effects can not easily be assessed and monitored in the presently available trials . in summary ,\nquestions about the efficiency and safety of iit in different icus around the world are far from answered and much work has still to be done to answer the new questions raised by the second leuven study .", "answer": "the second study on tight glycaemia control by intensive insulin therapy ( iit ) confirmed in medical intensive care unit patients the decrease in hospital mortality reported by the same team in the first iit trial in surgical patients . \n however , methodological concerns , the high rate of hypoglycaemia in spite of the infusion of large doses of parenteral glucose and the frequent use of steroids presently preclude considering these results as recommendations in other intensive care units , but rather argue for the need for large - scale assessment of the iit approach by multi - centre studies to confirm the efficacy and safety of this therapeutic modality .", "id": 722} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnon - specific odontogenic infections are among the most frequent disorders of bacterial origin that affect individuals during the course of their life . before antibiotic treatment was available , the mortality rate of these disorders was 1040% , but the discovery of antibiotics led to a significant improvement of this rate .\nhowever , the last 1015 years have witnessed a rebound of severe odontogenic infections caused by highly aggressive antibiotic - resistant bacteria .\nthe main cause indicated by the literature for the development of bacteria resistant to antibiotic therapy is the incorrect or inefficient administration of antibiotics .\ncurrently , a number of antibiotics for inflammatory dental pulp disorders or established abscesses are administered .\nthe efficiency of these antibiotics is extremely limited because of the circulation disorders present in the inflammatory focus and , in addition , there is a high risk for inducing adverse reactions and antibiotic resistance of the bacteria involved in the development of the septic process .\nfor this reason , we believe that it is extremely important to evaluate the way in which antibiotics are administered and their efficiency on the bacterial flora involved in the development of odontogenic suppurations , in the absence of surgery .\nthe aim of this study is to prospectively determine the type of antibiotics used by patients with odontogenic head and neck soft tissue infections , from the point of view of their efficiency on the bacterial flora involved in the development of the septic process .\nthe study included 10 randomly selected patients with suppurations of odontogenic origin who presented to the clinic of oral and maxillofacial surgery cluj - napoca in the period january 2014 july 2014 .\nthe patient selection criteria were : perimaxillary soft tissue infections of odontogenic origin , disease duration of at least 5 days , antibiotic treatment duration of at least 4 days , known type and mode of administration of antibiotic medication , antibiotic treatment prescribed by the family doctor or the dentist , patient treated under continuous hospitalization , patient from which biological samples were taken for bacteriological examination and antibiogram determination , no other systemic pathology types with a possible influence on the immune response , adult patient having signed an informed consent for participation in the study .\nthe variables monitored for each patient were : general data ( age , sex ) , location of infection , time from onset to presentation , type of antibiotic treatment and route of administration used , bacteriological examination and antibiogram result , postoperative evolution . after the emergency admission of the patients , surgery was performed under locoregional anesthesia . after the asepsis and antisepsis of the operative field ,\nbiological samples were collected in a closed environment and were subsequently sent for bacteriological examination and antibiogram determination .\nthe results obtained were centralized in the study data base . for the development of contingency tables , microsoft excel software\nwas used , and the statistical interpretation of the results was performed using microsoft excel .\nof the patients included in the study , 6 were males and 4 were females .\nthe mean age of the patients was 35.4 years , with a minimum age of 22 years and a maximum age of 49 years .\nthe mean age of female patients was 28.75 years and that of male patients 39.83 years .\nregarding the location of the septic process in perimaxillary soft tissues , the majority of the infections were located in the submandibular gland area , followed by those located in the genial region ( figs . 1 , 2 ) .\nin the case of the patients included in the study , a time period between 5 and 12 days , with a mean of 7.4 days , lapsed from the onset of the septic process to the presentation for specialized treatment . during this time period , all patients used antibiotic treatment , with a mean of 1.2 antibiotic types ; 8 of the 10 patients had one antibiotic type , and 2 patients had 2 antibiotic types .\n3 ) , and the most frequent route of administration was the oral route , only in two cases the antibiotics being administered by intravenous route .\nthe bacteriological result obtained from the purulent secretion samples collected from the septic focus evidenced microbial polymorphism ( tab .\ni ) . in half of the patients included in the study , the identified bacterial flora had no sensitivity to the antibiotics\n4 ) , and in one patient in whom several bacterial strains were detected , some of these were sensitive to the antibiotic administered to the patient .\nafter the incision and the drainage of the suppuration were performed , along with the change of the antibiotic scheme according to the antibiogram , the patients postoperative evolution was favorable .\nthe objectives of the study were reached and the main types of antibiotics administered to patients with odontogenic septic processes complicated by perimaxillary suppurations were determined .\nit can be seen that the majority of the patients included in the study were young adults , which is confirmed by other literature studies .\nauthors analyzing extensive groups of patients evidence the fact that odontogenic infections mainly affect patients in the third decade of life , which is confirmed in this study only by female patients , male patients having a more advanced age , but without a significant difference . of the patients included in the study ,\nhowever , it can not be concluded based on the presented data that the male sex is more frequently affected by cervical inflammatory disorders of odontogenic origin , because the patient inclusion criteria were very restrictive and the number of patients included in the study was limited .\nmost authors opine that there is a higher incidence of odontogenic infections among male patients , but the differences between the two sexes are extremely varied . regarding the antibiotics prescribed to the patients included in the present study , it can be seen that more than half of the patients received amoxicillin treatment with or without beta - lactamase inhibitors .\nthe majority of the patients took the antibiotic without beta - lactamase inhibitors , which is contrary to literature studies , which show that the main antibiotic administered for odontogenic infections is amoxicillin with beta - lactamase inhibitors .\nthe administration of an effective antibiotic in odontogenic infections is particularly important in the attempt to limit the septic process .\nwhen the antibiotic has no effect on the main bacterial strains involved in the development of the infection and only eliminates less aggressive pathogens , the premises for extremely severe and very difficult to control infections are created .\nbacteriological examination evidenced the presence of a varied bacterial flora , but in the majority of the cases , a single bacterial strain in each patient was obvious .\nthe presence of a single bacterial strain in each patient is surprising , given the fact that at the level of the infected dental pulp or periodontal space , the main sources of bacterial flora for odontogenic suppurations , an increased number of bacterial species are concomitantly identified .\nthus , it is possible that the early administration of bacterial therapy may select the majority of the bacterial species sensitive to the administered antibiotic and a single bacterial species may remain in the septic focus .\nthis hypothesis is also supported by the antibiogram result , which evidenced no sensitivity of the identified bacteria to the administered antibiotic .\nanother possible cause of the identification of a single bacterial strain might be the technical limitations of microbiology laboratories or the way of collecting biological samples , which pose difficulties in identifying some bacterial strains , particularly anaerobic ones .\nthe fact that most of the administered antibiotics were not active on the identified bacterial flora is an alarm signal .\nthe lack of efficiency of the antibiotic on the main bacterial strains involved in the development of the septic process implicitly leads to an increase of the difficulty of treatment of these infections .\nsome authors indicate the use of antibiotics as a single treatment , in the absence of a preliminary bacteriological examination , as the main factor favoring the development of severe odontogenic infections such as necrotizing fasciitis .\nthe exhaustion of the action of common antibiotics on the bacteria involved in the development of common cervical infections leads the practitioner to use niche antibiotics that should not be used under normal conditions .\na limitation of this study is the fact that it does not take into account possible cases of patients with odontogenic infections who received antibiotic treatment alone and who had a favorable evolution .\nthese cases can not be monitored in such studies because these patients do not ask for specialized help .\nmost common antibiotics used as a single therapy for the treatment of cervical infections of odontogenic origin have a limited action , and the association of antibiotic treatment with surgery is recommended .\nthe administration of antibiotics according to the bacteriological examination and antibiogram , associated with surgery , led to a favorable evolution of the patients included in this study .", "answer": "background and aims.odontogenic infections are among the main types of disorders located in the cephalic extremity . \n the aim of this study was to determine the efficiency of empirically administered antibiotics on the bacterial strains identified at the infection sites.patients and method.the study included 10 randomly selected patients with odontogenic cervical soft tissue infections , who received antibiotic treatment prescribed by the family doctor or the dentist . \n the bacterial flora involved in the development of the septic process , the type of antibiotic administered to the patient and the sensitivity of the identified bacterial flora to the administered antibiotic were determined.results.in the 10 selected patients , 14 bacterial strains were detected ; 7 patients had a single bacterial strain , and 3 patients had two or three types of bacteria . \n of the administered antibiotics , amoxicillin was the most widely used ( 33.3% of the cases ) , followed by amoxicillin with beta - lactamase inhibitors ( 25% of the cases ) . in half of the patients \n , there was no sensitivity of the bacteria detected in the septic focus to the empirically administered antibiotic , and in 10% of the cases , partial sensitivity was evidenced.conclusions.empirical administration of antibiotics without the association of surgery did not prove to be effective in the treatment of cervical infections of odontogenic origin .", "id": 723} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmyocardial bridging is defined as an epicardial coronary artery that goes intramurally through the myocardium beneath the muscle bridge . while generally benign , myocardial bridges can cause ischemia , ventricular tachyarrhythmias , atrioventricular block , and sudden cardiac death.1)2 ) for symptomatic patients , various therapeutic approaches have been attempted , but the optimal treatment of myocardial bridging still remains controversial.3)4 ) coronary stenting has been another therapeutic option with medical and surgical treatment , but the high risk of perforation and high rate of in - stent restenosis have limited its use.5 - 10 ) recently , we experienced a patient with a perforated coronary artery after implantation of a drug - eluting stent ( des ) that was successfully rescued by deployment of covered stent in symptomatic myocardial bridging .\na 46 year - old woman who had no coronary risk factors , presented with exertional chest pain for several weeks .\nthe chest pain was typical for angina pectoris and depressed st segments were noted at the exercise test .\nechocardiography revealed normal left ventricular ( lv ) systolic function { ejection fraction ( ef)=72% } without any regional wall motion abnormality .\nwe performed coronary angiography which showed significant stenosis ( up to 80% ) aggravated by severe myocardial bridging at the mid - portion of the left anterior descending ( lad ) artery ( fig .\nso we decided to do a percutaneous coronary intervention ( pci ) at the lad lesion . through a 7 fr judkins guiding catheter ,\npredilatation was performed with a maverick balloon catheter ( 2.515 mm , boston scientific , natick , ma , usa ) at 10 atmospheres for 20 seconds .\nwe deployed a taxus stent ( 3.516 mm , boston scientific , natick , ma , usa ) according to the size of the predilated balloon catheter .\nbut the middle segment of the lesion was not compliant , so the stent was not fully expanded with nominal pressure .\n, the coronary artery was perforated and some extravasation of contrast media was observed in the pericardium ( fig .\nbut , the patient 's vital signs were stable ( blood pressure 115/70 mmhg ) with only a mild increase in heart rate .\nhowever , because the perforated site was entrapped intramurally through the myocardium in the interventricular groove , there was no evidence of accumulated blood at the dependent position of the pericardium on fluoroscopy or echocardiography .\nso we decided to observe the patient with close monitoring of symptoms and vital signs .\nbut echocardiography showed no evidence of pericardial effusion . on an intravascular ultrasound ( ivus ) study , a large perforated site and a perivascular hematoma were observed in the mid - portion of the deployed stent ( fig .\n1c ) . based on the ivus findings , a jo covered stent ( 319 mm , jomed international ab , helsingborg , sweden ) was deployed at the perforation site .\nfour months after the procedure , ct angiography showed no evidence of residual hematoma or pseudoaneurysm ( fig .\n2a and b ) . follow - up coronary angiography performed at 8 months after the procedure showed good distal flow with minimal stenosis at the proximal edge of the stent ( fig . 2c ) .\nalthough coronary stenting is an effective interventional approach to improve symptoms in selected patients with myocardial bridging , it is associated with a high risk of coronary perforation.5 - 7 ) the reason for this phenomenon is not clear .\nautopsy findings showed that tunneled segments in myocardial bridging tend to be deficient in vascular smooth muscle density , which may be more prone to vascular disruption during high inflation pressures during pci.11)12 ) another study revealed that the vessel area in the myocardial bridge segment was significantly smaller than that in the adjacent reference segments proximal and distal to the myocardial bridge throughout the cardiac cycle.13 ) this finding might explain the higher rate of coronary perforation associated with coronary stent implantation for myocardial bridges .\nthe histological and anatomical differences in tunneled coronary arteries may require an adjustment in stent diameter and inflation pressures to help reduce the risk of coronary perforation . in our case , we selected an oversized stent , resulting in coronary perforation . pre - interventional ivus may be helpful in selection of an appropriate size of stent and , in particular , in cases that require high inflation pressures for optimal stent implantation .\nalthough coronary perforation is an uncommon complication following pci , it usually causes a catastrophic result including cardiac tamponade , emergency coronary artery bypass surgery , or pseudoaneurysm formation , with the potential for late coronary rupture and death.14)15 ) but , in myocardial bridging as observed in our patient , because the perforation site and extravasated blood are mainly confined in the interventricular groove , perforation itself usually does not cause hemodynamic instability .\nwe were able to evaluate the lesion using ivus to decide on implantation of a covered stent after perforation .\ncoronary stenting in myocardial bridging has been associated with a high restenosis rate.9 ) possible factors for this include shear stress from persistent external compression from myocardial bridges , causing neointimal proliferation , and long stent and recoil phenomena when inadequate pressures are used for stent deployment .\na des was chosen as a feasible alternative to surgery because it had the ability to reduce restenosis . in our case , we performed pci with a des , which also showed good distal flow with minimal restenosis at the proximal edge of the stent at follow - up angiography .\nour case showed that , even though coronary perforation had occurred in myocardial bridging , the perforation site was confined in the interventricular groove . therefore , it could be managed more easily than conventional coronary perforation .", "answer": "we successfully rescued a patient whose coronary artery perforated following implantation of a drug - eluting stent ( des ) , by deploying a stent - graft in symptomatic myocardial bridging . \n our case demonstrated that coronary perforation could be handled without difficulty when perforated myocardial bridging is confined to the interventricular groove", "id": 724} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngestational diabetes mellitus ( gdm ) is defined as abnormal glucose tolerance that is first identified or diagnosed during pregnancy .\nit is estimated that approximately 2% to 5% of all pregnancies in korean women are complicated by gdm .\nthe clinical significance of gdm is that it increases the risk of adverse pregnancy outcomes . in a recent large - scale multinational prospective study ,\nincreased maternal glucose concentration during pregnancy was significantly associated with increased neonatal birth weight , primary cesarean delivery , neonatal hypoglycemia , and increased placental c - peptide levels .\nafter parturition , about 15% of gdm women had persistent diabetes at an early postpartum period of 2 months .\nwomen with a previous history of gdm are at increased risk of future development of type 2 diabetes mellitus ( t2 dm ) .\nthe risk of t2 dm is 3.5 times greater in women with a history of gdm compared to the general population in koreans .\nin addition , offspring of gdm women are also at risk of developing obesity and t2 dm .\nthe incidence of gdm is expected to rise , as it will parallel the increasing rate of obesity and t2 dm .\nfurthermore , the recent recommendation from the international association of diabetes and pregnancy study group has lowered the diagnostic threshold of gdm and is expected to increase the incidence of gdm .\ngdm women have an increased positive family history of t2 dm . compared to pregnant women with normal glucose tolerance ,\ngdm women have a significantly greater parental history of t2 dm ( 13.2% vs. 30.1% , p < 0.001 ) .\nin addition , both gdm women and their offspring are at increased risk of future development of t2 dm . the heritability estimate of t2 dm was reported to be quite high ( h = 0.69 ) in a recent study performed in europeans .\nthese findings are indirect evidence that gdm has familial tendency . however , there is no study that has specifically evaluated the heritability of gdm using familial clustering or twins\n. it would be important to estimate the heritability of gdm and compare it with that of t2 dm in women .\nduring normal pregnancy , women experience increased adiposity and weight gain , which begin near mid - pregnancy and progress throughout the third trimester . in this period , insulin resistance ensues as a consequence of multiple factors , including increased production of placental growth hormone , estrogen , and tumor necrosis factor [ 14 , 15 ] .\npregnant women with normal glucose tolerance can increase their -cell insulin secretion in response to this increased insulin resistance during pregnancy .\nalthough the mechanism of increased -cell insulin secretion during pregnancy is not fully understood , it is reported that prolactin , which increases during pregnancy , can repress islet menin levels and stimulate -cell proliferation in mice .\nin addition , recent reports suggest that -cell serotonin signaling is also a major determinant of -cell mass during pregnancy .\nit has been suggested from several clinical studies that gdm women have limited insulin secretion capacity that can not compensate for the increased insulin resistance .\nsimilar to gdm , t2 dm is also characterized by relative deficiency in insulin secretion in the face of increased insulin resistance .\nvarious factors , including increased age , obesity , high - fat diet , and sedentary lifestyle , can induce insulin resistance , and those who do not have sufficient -cell insulin secretory capacity are more likely to develop t2 dm .\ntherefore , it is said that a large proportion of gdm women are experiencing future t2 dm in advance .\nbased on the findings that gdm women are at high risk of t2 dm and both gdm and t2 dm share similar pathophysiologies , it is reasonable to assume that they might also share similar genetic risk factors .\nsoon after the initial reports of t2 dm genome - wide association ( gwa ) studies [ 18 - 21 ] , several studies investigated whether genetic variants that were identified through gwa studies of t2 dm were also associated with the risk of gdm [ 22 , 23 ] .\ngenotyped variants in or near cdkal1 , cdkn2a/2b , fto , hhex , igf2bp2 , slc30a8 , tcf7l2 , kcnj11 , and pparg in 869 gdm women and 632 carefully selected nondiabetic control subjects .\nthey found that genetic variants in cdkal1 and cdkn2a/2b were highly associated with the risk of gdm ( p < 1 10 ) .\nin addition , variants in hhex , igf2bp2 , slc30a8 , and tcf7l2 were all nominally associated with gdm ( p < 0.05 ) . among a total of 18 genetic variants studied , 9 reached a nominal significance level ( p < 0.05 ) . in fig .\n1 , the risk allele frequency as well as the odds ratios of known t2 dm variants are compared among a control group ( n = 632 , men : women = 287 : 345 ) , t2 dm group ( n = 761 , men : women = 354 : 407 ) , and gdm group ( n = 869 ) in koreans [ 22 , 24 ] . for most of the variants ,\nthere was an increasing trend of risk allele frequencies from control to t2 dm and from t2 dm to gdm .\n. also found that variants in tcf7l2 , cdkal1 , and tcf2 were significantly associated with the risk of gdm in europeans , consisting of 283 gdm women and 2,446 glucose - tolerant control women .\nvariants in kcnq1 , which were first identified in an east asian t2 dm gwa study , were also significantly associated with the risk of gdm in koreans ( p < 0.05 ) .\nrecently , it was reported that tph1 and htr2b play a crucial role in regulating pancreatic -cell mass during pregnancy in a mouse model and that their genetic alterations could result in gdm .\na total 6 genetic variants in htr2b and 11 variants in tph1 were identified and genotyped in korean gdm women and control subjects .\nalthough there were no significant associations of these variants with the risk of gdm , they were associated with measures of obesity and weight gain during pregnancy .\nfollowing these candidate approach studies was a two - staged gwa study that was performed in korean gdm women .\na total of 468 gdm women and 1,242 nondiabetic control women were genotyped using affymetrix genome - wide human snp array 5.0 .\nvariants that passed the prespecified p - value threshold in the stage 1 genome scan were further genotyped in 931 gdm women and 783 nondiabetic control women .\ntwo variants , one located in an intron of cdkal1 ( rs7754840 ) and one near mtnr1b ( rs10830962 ) , were associated with a risk of gdm at a genome - wide significance level ( p = 6.65 10 and p = 2.49 10 , respectively ) .\nalthough variants in mtnr1b have been previously reported to be associated with increased fasting glucose levels , the study was the first to report that mtnr1b variants are associated with gdm at a genome - wide significance level .\none of the limitations was that it was not sufficiently powered to find truly novel genetic variants that were only specific in gdm .\nit should be noted that current gwa and gwa meta - analysis performed in t2 dm recruits more than 100,000 cases and controls .\none of the interesting findings was that genetic variants of t2 dm were enriched in gdm subjects . among\nthe 34 confirmed t2 dm genetic variants , 8 were associated with a risk of gdm .\nin addition , when the -coefficients ( or odds ratio ) of the variants derived from the logistic regression were compared between gdm and t2 dm , there was a significant positive correlation of -coefficients between the two .\nthese findings suggest that gdm and t2 dm might share similar genetic backgrounds , at least in part .\ngwa studies have opened a new era in diabetes research . our knowledge on the genetic predisposition of gdm as well as t2 dm\nis expected to increase even faster as next - generation sequencing technology is applied to this field .\nthere should be even larger gwa studies on gdm , and gwa meta - analyses should be available . in this way , we could find variants that have smaller effect sizes but are more specific to gdm than t2 dm . in order to understand the genetic determinants of glucose and insulin concentration during pregnancy ,\na fast way is to see whether genetic variants that are known to affect glucose or insulin concentration in the normal population also affect glucose or insulin concentration during pregnancy .\nin addition , a gwa study on glucose or insulin concentration during pregnancy should also be helpful .\nin this way , we would be able to better understand the pathophysiology of gdm . by definition\n, gdm encompasses women with pre - exiting t2 dm , maturity onset diabetes of the young ( mody ) , or even type 1 diabetes patients that were not diagnosed previously .\nin particular , about 15% of gdm patients remain diabetic at early postpartum periods , and a significant portion of these subjects might fall into the category of mody .\nthe contribution of genetic variants known to cause mody , such as gck and hnf1a , in gdm has been reviewed in recent literature .\nhowever , whole - exome sequencing will provide us with better bird 's eye view on the contribution of mody genes in gdm .\nin addition , it might be able to find novel mody genes in those who have persistent diabetes after gdm pregnancy and also have a strong family history of diabetes .\none of the first steps in translating the genetic information into clinical practice would be to predict the future development of t2 dm in gdm women .\ngdm women are at particularly high risk of developing t2 dm and require preventive measures and early screening of t2 dm .\ngenetic information might improve our prediction of t2 dm in women with a history of gdm .\nthis is an area of active research [ 31 , 32 ] , and we are looking forward to studies that use genotype risk scores in predicting t2 dm in gdm women\n. a similar approach could also be applied in predicting gdm , as more genetic variants associated with gdm are expected to be revealed .\nthe functional consequences of the current common genetic variants identified through gwa studies of gdm are not well understood yet .\nit is not known whether they are markers in linkage disequilibrium with nearby causal variants or whether they have unknown but relevant functional roles .\nnext - generation sequencing might give answers to these questions , but a huge number of samples and much effort will be required .\ngdm women are at increased risk of developing t2 dm and have familial clustering of t2 dm . a common pathophysiology that is shared by gdm and t2 dm is impaired compensatory increase in insulin secretion to overcome the increased insulin resistance .\nthe gwa study of gdm enabled us to investigate the common genetic risk factors of gdm , and it revealed that gdm and t2 dm share similar genetic backgrounds , at least in part ( fig .\nalthough this information has significantly improved our insight in the pathogenesis of gdm , there are more unanswered questions remaining that should be explicitly expressed . using the technology of next - generation sequencing\nin addition , we hope that personalized genomic medicine could be available using the advances in the genetics of gdm and t2 dm .", "answer": "gestational diabetes mellitus ( gdm ) is a complex metabolic disorder of pregnancy that is suspected to have a strong genetic predisposition . \n it is associated with poor perinatal outcome , and both gdm women and their offspring are at increased risk of future development of type 2 diabetes mellitus ( t2 dm ) . during the past several years \n , there has been progress in finding the genetic risk factors of gdm in relation to t2 dm . \n some of the genetic variants that were proven to be significantly associated with t2 dm are also genetic risk factors of gdm . recently , \n a genome - wide association study of gdm was performed and reported that genetic variants in cdkal1 and mtnr1b were associated with gdm at a genome - wide significance level . \n current investigations using next - generation sequencing will improve our insight into the pathophysiology of gdm . \n it would be important to know whether genetic information revealed from these studies could improve our prediction of gdm and the future development of t2 dm . we hope further research on the genetics of gdm would ultimately lead us to personalized genomic medicine and improved patient care .", "id": 725} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiabetes mellitus ( dm ) is a group of disorders associated with a quantitative reduction in insulin production or a qualitative reduction in the action of insulin leading to changes in carbohydrate , protein , and lipid metabolism and accumulation of glucose in the bloodstream .\nthe prevalence of type 2 diabetes for all age groups worldwide was 2.8% in 2000 and estimated to be 4.4% in 2030 .\nthe prevalence rate of diabetes in india in urban areas is 9% , in rural areas also increased to 3% of the total population , and the ratio of patients with unknown to known diabetes is 1.8:1 .\nthis can be primarily attributed to the fact that the condition is usually undetected in its early stages in most individuals , whereas in other individuals , the existing symptoms are often overlooked because of ignorance or negligence on the part of the patient .\nclinical studies have established that periodontal diseases are more prevalent and of greater severity in patients with diabetes than in nondiabetic patients .\nscreening for diseases is to identify those who have an increased likelihood of developing a disease or experiencing an increase in disease severity as a first step in disease prevention and control .\nthere will be a greater likelihood of a favorable prognosis when a disease is discovered while it is still relatively incipient .\nthe early diagnosis of diabetes , however , might help to prevent its long - term complications that are responsible for the high morbidity and mortality of diabetes patients . to our knowledge , there are very limited studies on screening of undiagnosed diabetes with gingival blood in dental patients .\ntherefore , the aim of this study is screening of undiagnosed diabetes with gingival blood sample in patients attending to the dental hospital and to check the reliability with standard method .\nafter receiving the approval of the ethical committee , rmdc and h , 550 patients age ranged from 30 to 50 years were randomly selected from the outpatient department of periodontics .\npatients with no known previous history of diabetes and having any risk factors like family history of diabetes , hypertension , high cholesterol , overweight / obesity with at least one tooth that bleed on probing were included in the study .\npatients with known diabetes , pregnancy , any other systemic diseases were excluded from the study .\npatients either with known diabetes ( n = 32 ) or with no gingival bleeding ( n = 28 ) were excluded from the study .\na special case history proforma was prepared for a systematic and methodical recording of all observations which included a detailed case history and clinical examination , along with the written consent of the patient for willingness to participate in the study .\nfor all the 454 patients , a gingival blood sample was collected from bleeding site with the help of a small plastic syringe and analyzed with self - monitoring device .\na minimum of 0.3 l of blood is required for assessment of blood glucose using self - monitoring device ( one touch , johnson and johnson ) .\nin addition , all the patients were advised for the second visit with overnight 8 h fasting for fasting blood glucose assessment .\nfour patients who were found to be diabetic and eight patients who were found to be nondiabetic by chair side assessment failed to report for further assessment . of those 442 ( 202-males , 240-females ) patients returned for fasting blood glucose assessment in laboratory with ( digital colorimeter , elico cl157 ) patients with abnormal blood glucose values were advised to consult a physician for appropriate care [ figure 1 ] .\noutline of study design blood glucose values of all the patients were subjected to descriptive statistical analysis with spss version 16 software ( chicago , il , usa ) .\nnumber of patients identified as prediabetes and diabetes were analyzed for both self - monitoring glucose meter assessment and laboratory blood glucose assessment .\nafter receiving the approval of the ethical committee , rmdc and h , 550 patients age ranged from 30 to 50 years were randomly selected from the outpatient department of periodontics .\npatients with no known previous history of diabetes and having any risk factors like family history of diabetes , hypertension , high cholesterol , overweight / obesity with at least one tooth that bleed on probing were included in the study .\npatients with known diabetes , pregnancy , any other systemic diseases were excluded from the study .\npatients either with known diabetes ( n = 32 ) or with no gingival bleeding ( n = 28 ) were excluded from the study .\na special case history proforma was prepared for a systematic and methodical recording of all observations which included a detailed case history and clinical examination , along with the written consent of the patient for willingness to participate in the study .\nfor all the 454 patients , a gingival blood sample was collected from bleeding site with the help of a small plastic syringe and analyzed with self - monitoring device .\na minimum of 0.3 l of blood is required for assessment of blood glucose using self - monitoring device ( one touch , johnson and johnson ) .\nin addition , all the patients were advised for the second visit with overnight 8 h fasting for fasting blood glucose assessment .\nfour patients who were found to be diabetic and eight patients who were found to be nondiabetic by chair side assessment failed to report for further assessment . of those 442 ( 202-males , 240-females ) patients returned for fasting blood glucose assessment in laboratory with ( digital colorimeter , elico cl157 ) patients with abnormal blood glucose values were advised to consult a physician for appropriate care [ figure 1 ] .\nblood glucose values of all the patients were subjected to descriptive statistical analysis with spss version 16 software ( chicago , il , usa ) .\nnumber of patients identified as prediabetes and diabetes were analyzed for both self - monitoring glucose meter assessment and laboratory blood glucose assessment .\nmean age of the patients investigated is 42.45 6.60 . in the 454 patients gingival blood glucose assessment with self - monitoring device\n, 64 patients showed 200 mg / dl which indicates diabetes , and the other 390 patients showed 200 mg / dl , which indicates patients are not diabetic .\nwhereas , the results of the laboratory blood glucose analysis , 24 ( 5.43% ) patients showed 126 mg / dl which indicates diabetes , 36 ( 8.14% ) ( patients showed 100125 mg / dl which indicates prediabetic state and the other 382 patients are not diabetic ( < 100 mg / dl ) . among the 240 male patients 13 patients were diabetic and 20 were in prediabetic status and in 202 female patients , 11 patients were diabetic and 16 were in prediabetic status [ table 1 ] .\nwhen compared male and females in both methods , chi - square test values were not significant [ table 2 ] .\ntable 3 shows the comparison of gingival blood sample measurement with laboratory blood glucose assessment .\ncomparison of gingival blood sample measurements obtained by glucometer with the blood sample assessed in the laboratory showed sensitivity 96.6% and specificity 99.47% [ table 3 ] .\ndistribution and percentage of patients investigated as prediabetes , diabetes comparison of blood glucose assessment by two methods in male and females comparison of the gingival blood sample measurements obtained by glucometer with blood sample assessed in laboratory we also considered the risk factors for diabetes , 122 patients were with risk factors and 320 patients were without any risk factors .\nthe prevalence of risk factors [ figure 2 ] like hypertension , sedentary lifestyle , family history , and overweight was significantly higher in the patients with abnormal blood glucose levels .\nearly detection and treatment of dm may reduce the burden of diabetes and its complications .\nthis is most important in a high - risk population . screening for diabetes should start at 40 years of age and to be repeated every 3 years in persons without risk factors , and earlier and more often in those with risk factors for diabetes .\nunfortunately , more than 50% of the diabetic subjects in india remain unaware of their diabetes status , which adds to the disease burden .\nthis underscores the need for mass awareness and screening programs to identify and reduce the burden due to diabetes in india .\nthe results of this study conducted to screen patients with diabetes in the dental hospital using gingival blood with self - monitoring device showed 64 ( 13.2% ) patients were with abnormal blood glucose levels , which indicate as diabetic . when the same patients subjected to laboratory fasting blood glucose assessment ,\n60 patients were with abnormal blood glucose levels ( 8.14% showed prediabetic status and 5.43% is diabetic ) . among the 202 male patients , 33 patients showed abnormal blood glucose levels suggestive of diabetes , whereas 240 female patients were screened for diabetes 27 patients were with abnormal glucose levels .\nthis increase in the number of females with abnormal glucose levels may be due to greater psychological stress in asian women as suggested by the authors in their study .\nwhen the risk factors are taken into account , 122 patients were associated with risk factors and 320 patients were without any risk factors .\nprevalence of diabetes is significantly associated with risk factors . in a study conducted by the authors , prevalence of risk factors in urban areas\nthere is higher prevalence of risk factors such as smoking , obesity , hypertension dyslipidemia , sedentary habits and metabolic syndrome . in a longitudinal study from urban india smoking and sedentary habits\nthe role of obesity in the pathogenesis of type 2 diabetes is complex and is confounded by many heterogeneous factors . in a study conducted in north india concluded that there was a strikingly high prevalence of abdominal obesity and generalized obesity as determined by body fat percentage in type 2 diabetic individuals .\nprimary disease prevention and control activities are meant to delay disease onset and control disease severity .\nthere is a huge window of opportunity for prevention , considering the number of modifiable risk factors among the prediabetes group only when the prediabetic stage is identified at earlier , in which periodontist has a key role .\nauthors developed a clinical guidelines for dental care providers to identify patients with undiagnosed diabetes by means of a periodontal disease examination , as well as asking questions about self - reported or self - measured waist circumference , self - reported age , self - reported weight , self - reported oral health status , self - reported race or ethnicity and family history of diabetes . in view of the growing number of people with undiagnosed diabetes and the increased risk for periodontal patients ,\ndiabetes screening at the time of the dental visit seems to offer a promising approach .\nthe limitation of the study includes as with most diagnostic tests , an abnormal result should be repeated to rule out laboratory error and should be coupled with an evaluation by a physician before a diagnosis can be made .\nthe results of the present study showed blood obtained from periodontal pocket probing is a reliable sample to screen diabetes in periodontal disease population .\nearly diagnosis of diabetes in the dental hospitals can help improve the patient 's oral health and overall health status by helping patients avoid or reduce complications from diabetes .\nhowever , the present study could also be carried out with a larger survey population for a more effective screening .", "answer": "background : early detection and treatment of diabetes mellitus may reduce the burden of diabetes and its complications . \n screening of undiagnosed diabetes with gingival blood sample in patients attending to the dental hospital and to check the reliability with standard method.methods:five hundred and fifty new patients age ranged from 30 to 50 years were randomly selected . \n of 550 patients examined , gingival blood samples of 454 patients were collected from bleeding site and analyzed with self - monitoring device . \n blood glucose values were recorded . \n in addition , all the patients were advised for the second visit with overnight fasting for fasting blood glucose assessment . among them \n , 442 patients returned for fasting blood glucose assessment in laboratory with blood glucose analyzer.results:in the total of 454 patients gingival blood glucose assessment with self - monitoring device , 64 patients showed 200 mg / dl , which indicates diabetes , and the other 390 patients showed 200 mg / dl , which indicates patients are not diabetic . \n whereas , the results of the laboratory blood glucose analysis , 24 ( 5.43% ) patients showed 126 mg / dl , 36 ( 8.14% ) patients showed 100125 mg / dl and the other 382 patients are not diabetic . \n comparison of blood glucose measurements by two methods showed sensitivity 96.66% and specificity 99.47%.conclusions : the results of the present study showed blood obtained from periodontal pocket probing is a reliable sample to screen diabetes in periodontal disease population . \n early diagnosis of diabetes in the dental hospitals can help improve the patient 's oral health and overall health status by helping patients avoid or reduce complications from diabetes .", "id": 726} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfemoral and humeral bones of balb / c mouse embryos were removed aseptically on 18.5 dpc , and they were microdissected into esz and growth plate ( egp ) under a stereomicroscope ( zeiss stemi 2000-c , carl zeiss microimaging ) .\neach region was minced and gently digested with 2 mg / ml of collagenase ( wako pure chemical ) at 37 c for 2 h. they were cultured in growth medium composed of iscove 's modified dulbecco 's medium ( invitrogen ) supplemented with 15% fetal bovine serum , and subjected immediately to retroviral infection .\nfli1 was introduced into the pmys - ires - gfp vector . the full length ews \nthe per cell normalization method ( percellome method ) was applied to esz and egp samples .\na 10 l aliquot of each lysate was treated with dnase - free rnase a ( nippon gene inc . ,\njapan ) for 30 min at 37 c , followed by proteinase k ( roche diagnostics gmbh .\nusa ) was added to each well , shaken for 10 s four times and then incubated for 2 min at 30 c .\ndna concentration was measured using a 96 well fluorescence plate reader with excitation at 485 nm and emission at 538 nm .\nusa ) was used as standard . as reported previously , the grade - dosed spike cocktails ( gscs ) made of the bacillus subtilis rnas corresponding to the sequences in the affymetrix genechip arrays ( affx - thrx-3_at , affx - lysx-3_at , affx - phex-3_at , affx - dapx-3_at , and affx - trpnx-3_at ) were prepared , and gscs were added to the sample homogenates in proportion to their dna concentrations .\nthe genechip mouse genome 430 2.0 array ( affymetrix ) was hybridized with the crna generated from esz and egp cells , and murine ewing 's sarcoma tissue ( table 1 ) . after staining with streptavidin \nphycoerythrin conjugates , arrays were scanned using an affymetrix genechip scanner 3000 and analyzed using affymetrix genechip command console software ( agcc , affymetrix ) and genespring gx 11.0.2 ( agilent technologies ) as described previously .\nthe expression data for esz and egp cells were converted to percellome data , i.e. , absolute copy numbers of mrna per one cell , by the homemade software scal4 ( spike calculation version 4 ) .\nresponse linearity of the five gsc spikes and the location of spike probe sets in the histogram of all probe sets ( fig . \nn = 3 ) , all the pairs were plotted to a scatter graph as red ( expression above detection level ) or green dots ( below detection level ) with the data of five yellow spike probe sets ( fig . \nif any samples did not draw a symmetric scatter plot with yellow dot on the diagonal line , the sample were rejected for evaluation , and they were subjected to additional analyses .\nhomemade software named rsort ( roughness sort ) was used . this program sorts the probe sets as upward or downward peaks in a 3d isobologram ( fig . 2 ) . to avoid biologically nonsense\nprobe sets such as ones with expression below the detection level , the data were visually checked for their 3d isobologram shape .\nfemoral and humeral bones of balb / c mouse embryos were removed aseptically on 18.5 dpc , and they were microdissected into esz and growth plate ( egp ) under a stereomicroscope ( zeiss stemi 2000-c , carl zeiss microimaging ) .\neach region was minced and gently digested with 2 mg / ml of collagenase ( wako pure chemical ) at 37 c for 2 h. they were cultured in growth medium composed of iscove 's modified dulbecco 's medium ( invitrogen ) supplemented with 15% fetal bovine serum , and subjected immediately to retroviral infection .\nfli1 was introduced into the pmys - ires - gfp vector . the full length ews \nthe per cell normalization method ( percellome method ) was applied to esz and egp samples . briefly\na 10 l aliquot of each lysate was treated with dnase - free rnase a ( nippon gene inc . ,\njapan ) for 30 min at 37 c , followed by proteinase k ( roche diagnostics gmbh .\nusa ) was added to each well , shaken for 10 s four times and then incubated for 2 min at 30 c .\ndna concentration was measured using a 96 well fluorescence plate reader with excitation at 485 nm and emission at 538 nm .\nusa ) was used as standard . as reported previously , the grade - dosed spike cocktails ( gscs ) made of the bacillus subtilis rnas corresponding to the sequences in the affymetrix genechip arrays ( affx - thrx-3_at , affx - lysx-3_at , affx - phex-3_at , affx - dapx-3_at , and affx - trpnx-3_at ) were prepared , and gscs were added to the sample homogenates in proportion to their dna concentrations .\nthe genechip mouse genome 430 2.0 array ( affymetrix ) was hybridized with the crna generated from esz and egp cells , and murine ewing 's sarcoma tissue ( table 1 ) . after staining with streptavidin \nphycoerythrin conjugates , arrays were scanned using an affymetrix genechip scanner 3000 and analyzed using affymetrix genechip command console software ( agcc , affymetrix ) and genespring gx 11.0.2 ( agilent technologies ) as described previously .\nthe expression data for esz and egp cells were converted to percellome data , i.e. , absolute copy numbers of mrna per one cell , by the homemade software scal4 ( spike calculation version 4 ) .\nresponse linearity of the five gsc spikes and the location of spike probe sets in the histogram of all probe sets ( fig . \nn = 3 ) , all the pairs were plotted to a scatter graph as red ( expression above detection level ) or green dots ( below detection level ) with the data of five yellow spike probe sets ( fig . \nif any samples did not draw a symmetric scatter plot with yellow dot on the diagonal line , the sample were rejected for evaluation , and they were subjected to additional analyses .\nhomemade software named rsort ( roughness sort ) was used . this program sorts the probe sets as upward or downward peaks in a 3d isobologram ( fig . 2 ) . to avoid biologically nonsense probe sets such as ones with expression below the detection level ,\nwe describe a unique dataset of mouse embryonic cartilage with or without the ewing 's sarcoma fusion oncogene , ews fli1 .\nthe dataset was used in the study published recently and was informative to understand the tumorigenic mechanisms of ewing 's sarcoma .", "answer": "ewing 's sarcoma is a rare bone tumor that affects children and adolescents . \n we have recently succeeded to induce ewing 's sarcoma - like small round cell tumor in mice by expression of ews ets fusion genes in murine embryonic osteochondrogenic progenitors . \n the ewing 's sarcoma precursors are enriched in embryonic superficial zone ( esz ) cells of long bone . to get insights into the mechanisms of ewing 's sarcoma development , gene expression profiles between ews \n fli1-sensitive esz cells and ews \n fli1-resistant embryonic growth plate ( egp ) cells were compared using dna microarrays . \n gene expression of esz and egp cells ( total , 30 samples ) was evaluated with or without ews \n fli1 expression 0 , 8 or 48 h after gene transduction . \n our data provide useful information for gene expression responses to fusion oncogenes in human sarcoma .", "id": 727} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noral myiasis is a rare condition that refers to the invasion of tissue of the oral cavity by fly larvae .\nthe term myiasis ( greek : myia= fly , iasis = disease ) was coined by hope in 1840 and it was first described by laurance in 1909 .\nzumpt defined myiasis as the infestation of live human and vertebrate animals with dipterous larvae , which feed on living or necrotic tissues , liquid body substances , or ingested food .\nhuman myiasis is reported mainly in developing countries such as asian countries and very rarely from western countries .\nmyiasis can be classified depending on the condition of the involved tissue as i ) accidental myiasis when larvae get ingested along with food , ii ) semi - specific myiasis when the larvae are laid on necrotic tissue of the wound and iii )\n. based on anatomic site , it can be classified as i ) cutaneous myiasis , ii ) myiasis of external orifices and iii ) myiasis of internal organs .\nprimary myiasis is caused by biophagous larvae ( feed on living tissues ) and also called as obligatory myiasis .\nsecondary myiasis is caused by the necrobiophagous larvae ( feed on dead tissues ) and also called as facultative myiasis .\nthe most common anatomical sites for myiasis are the nose , eyes , skin wounds , sinuses , ears , lungs , gut , gall bladder , vagina , nasal cavities , and rarely , the mouth . whereas cutaneous myiasis involves invasion of the skin through the wounds .\nthe common predisposing factors are incompetent lips , poor oral hygiene , severe halitosis , anterior open bite , mouth breathing during sleep , facial trauma , extraction wounds , ulcerative lesions and carcinoma .\nmost of the patients are senile , alcoholics , mentally handicapped , cerebral palsied,[121416 ] and also those living in poor conditions , with no age limitation .\ndroma etal . reported that incidence of myiasis is more in anterior maxillary region and men are more affected than women .\ntraumatic wounds in orofacial region , when neglected by patients themselves as well as care takers , can lead to development of myiasis .\nthe present report describes a case of oral myiasis in a 14 year old boy with a history of trauma to the maxillary anterior region and it was neglected by him and parents .\na 14 year old boy with learning disability presented to department of pedodontics and preventive dentistry , sjm dental collegeand hospital , chitradurga , with a chief complaint of upper lip swelling and itching sensation on the right side of the face since more than 2 weeks [ figure 1 ] .\nthe patient gave a history of trauma to maxillary anterior dentoalveolar region and it was neglected for many days . on examination , there was swelling of the face on the right side , which extended from infraorbital region to upper lip [ figure 1 ] .\nintraoral examination revealed a deep lacerated wound which was infected and maggots were noticed on the upper vestibule and the nasal floor .\nthe patient had an incompetent lip , swollen upper gingiva , and poor oral hygiene , and general symptoms like pain , fever and malaise were present .\na cotton swab impregnated with turpentine was placed near the upper vestibule ( wound ) area for 510 minutes .\nmany of the maggots came out from the nose , which were then removed one by one with the help of curved artery forceps [ figures 2 , 3 ] . during the 3 days interval ,\nthe length of the each maggot ranged from 6 to17 mm [ figure 6 ] .\nthen , the wound was irrigated with hydrogen peroxide , antiseptic betadine solution and broad - spectrum antibiotics , and analgesics were prescribed .\nthe patient was recalled for regular follow - up for wound debridement and the wound healed uneventfully .\nswelling of the right side of the face and the upper lip arrow shows larvae coming out from the nose number of maggots removed from this area collected larvae from the lesion each maggot was measured\nmyiasis is an uncommon disease in humans and common in rural areas compared to urban areas .\nthe most common sites are the nose , eye , ear , anus , vagina , and rarely , the oral cavity .\npredisposing factors are extraction wounds , poor oral hygiene , psychiatric patients , mouth breathing during sleep , facial trauma , open neglected wounds , necrotic tissues , suppurative lesions , severe halitosis , senility , cerebral palsy , mental retardation , hemiplegia and factors that favor persistent non - closure of the mouth.[121416 ] primary oral myiasis commonly affects the anterior part of the mouth .\nthe patient reported here was residing in a rural area , with low socioeconomic background .\nthe life cycle of a house fly begins with the egg stage followed by the larva , the pupa , and finally the adult fly .\nthe conditions required for egg laying and survival of the larvae are moisture , necrotic tissue and suitable temperature .\nthe larval stage lasts from 6 to 8 days , in which period they are parasitic to human beings .\nthey are photophobic , and therefore tend to hide deep into the tissues , which also helps them to secure a suitable niche to develop into pupa . in the present case also , the larvae were present deep into the tissue and the nasal floor .\nproteolytic enzymes released by the surrounding bacteria decompose the tissue and the larvae feed on this rotten issue .\noral myiasis can also be classified as- 1 ) larvae living outside the body , 2 ) larvae burrow into unbroken skin and develop under it .\n4 ) eggs or young larvae are deposited in the wounds or natural cavities in the body .\nwhen there are multiple larvae and in advanced stages of development and there is tissue destruction , local application of various agents like turpentine oil , larvicidal drug like negasunt , ethyl chloride , ether , mercuric chloride , creosote , saline , iodoform , chloroform , clove oil , calomel , phenol mixture , olive oil , gentian violet , alcoholic solution in association with tobacco , camphor , sodium hypochlorite can be used for complete removal of all larvae .\nthese agents asphyxiate the aerobic larvae and force them to a superficial position and these larvae are removed with less damage to tissues and larvae as well .\nthe rupture of the larvae might cause allergic or foreign body reaction and secondary infection , so care must be taken not to rupture the maggots . in the present case , maggots were removed completely in 3 days interval by using turpentine oil .\nmyiasis of orofacial region can be prevented by educating the people from rural areas and low socioeconomic groups about personal hygiene , taking care of any wound , control of fly population and maintenance of sanitation of the surroundings .\nwe , the dentists , must educate parents / guardians to make them aware of the conditions , and the parents should bring children as early as possible for dental intervention to prevent further complications .", "answer": "oral myiasis is a rare condition in humans and is associated with poor oral hygiene , severe halitosis , mouth breathing during sleep , mental handicap , cerebral palsy , epilepsy , anterior open bite , incompetent lips , and other conditions . in this report , a 14 year - old boy who had an orofacial trauma in the maxillary dentoalveolar region , which was neglected , has been described . \n there was a deep lacerated wound on the upper vestibule which was infected and maggots were found on the same wound . \n the clinical features , management , treatment are discussed and relevant literature is reviewed .", "id": 728} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noverweight and obesity are conditions that have been increasing in the united states and these risk factors for diseases are estimated to affect more than one - half of those over the age of 20 . over the last few years\nobesity is a major public health concern because it increases the risk for many chronic conditions , such as cardiovascular diseases , particularly diabetes , hypertension , coronary artery disease , and cancer [ 1,811 ] .\npublic health officials have begun to monitor the health status of school - aged children because it is believed that many of them exhibit risk factors that create the potential for developing chronic disease as adults . in 1994 ,\n10.4% among 2 to 5-year - old children , compared to 11.3% and 7.2% respectively for the same age groups in 1988 .\nthis increase in overweight children has underscored the challenges faced by young people as they grow into an adult group where over 50% are overweight , and at significant risk for developing cardiovascular and other metabolic disorders [ 1 , 12 ] .\neffective management of risk factors among the youth , such as reducing / eliminating improper dietary practices and incorporating adequate physical activity , must become a universal health priority in order to effectively precipitate any noticeable decline in the adult morbidity and mortality statistics .\nchildhood obesity is also associated with several immediate health risk factors , such as orthopedic , neurological , pulmonary , gastroenterological , and endocrine conditions .\nobesity has been linked to negative psychosocial outcomes in children , such as low self - esteem and depression [ 1523 ] , making obesity indirectly linked to academic performance and adverse social outcomes over time [ 2429 ] .\ncardiovascular disease is not only the leading cause of death , but also the single greatest contributor to excess mortality in african - americans .\nunhealthy eating contributes to at least 300,000 preventable deaths each year , and is one of the most identifiable contributors to premature death , second only to tobacco use .\npremature deaths due to cardiovascular disease remain higher for african americans than any other group [ 3137 ] .\nthe highest rates of premature coronary heart disease in adults age 3564 occurred in the rural southern region of the united states .\nthe rate of cvd for african americans in mississippi was deemed serious enough to compel the national institutes of health ( nih ) to initiate the jackson heart study to focus on identifying risk factors for the development of cvd in african - americans . among the known risk factors for cvd\naccording to tom walden of the north american association for the study of obesity , schools can play a key role in preventing the risk behaviors by providing instruction on proper nutrition and physical activity .\nbased on this premise , this study was designed to examine the students possible role in changing their own negative practices , by first assessing their perceptions of the obstacles to positive dietary practices and increased physical activity .\nthe study also solicited students recommendations for reducing the negative practices that are associated with the rise in obesity and the development of cardiovascular diseases .\nthe implementation of the study was intended to grant the students an opportunity to provide their own ideas , suggestions and recommendations for what they feel could be done to improve their quality of life and to prevent premature morbidity and mortality .\nthe sample for this study included 300 students from a high school , located in rural , mississippi .\nthe high school under investigation in this study educates students in grades 912 , and all students enrolled in the health and physical education courses comprised the sample for this project .\nstudents were first asked to complete an assent form and to have their parents sign a consent form before they could participate in the survey .\nonly students who returned completed assent and consent forms were permitted to participate in the study .\nthe data for the study were obtained from the administration of the project health high school survey ( phhss ) , which was a modification of the mississippi youth risk behavior survey ( yrbs ) that was developed by the centers for disease control and prevention ( cdc ) .\nthe phhss was designed to measure the prevalence of risk behaviors associated with leading causes of illness and death .\nthe survey was modified to include three additional questions that served to fulfill the objectives of this study .\nthese questions specifically asked students to respond about their perceptions , and were the following : \nwhat do you think is keeping you or other students from eating more nutritious , healthier foods ?\n what do you think is preventing you or other students from taking part in daily physical activity ? what suggestions do you have that would help students to start eating better and exercising more ? these were open - ended questions and the students had the freedom to think and enumerate their perceptions .\nthe students were assured that their responses would be confidential and their honest responses could shed some light on a perplexing health dilemma that currently faced public health officials .\nall students enrolled in health and physical education classes , which included students in the 912 grades , were administered the phhss survey during the regular classroom session by the regular health and physical education teacher .\nthe students responses on each of these issues were recorded and analyzed to fully understand their perceptions and recommendations .\nthis descriptive study sought to ascertain the students perceptions through the use of questions that were presented in the form of a self - administered questionnaire . upon completion of the survey ,\nthe statistical package for the social sciences ( spss ) was used to evaluate the student responses .\nthe high school students perceptions about current practices and possible solutions were calculated and presented in the tables that follow .\nthe students perceptions on each of the areas under investigation were recorded and reported based on the rankings ( highest number of responses received and recorded ) from highest to lowest .\ncompleted phhss surveys were returned for 126 students which represented 42% of the 300 students enrolled in the health and physical education classes .\nall of the students were between the ages of 14 and 18 , and they were all enrolled in grades 912 .\nthe breakdown according to race was as follows : 94.9% were african american ; 2.5% were hispanic ; 1.3% were asian ; and 1.3% were native americans , the participants were 69% female and 31% male .\nstudents at the high school were asked to respond to the question what do you think is keeping you or other students from eating better ( more nutritious foods ? figure 1 provides a graphical image of the students responses about this issue .\nlove of sweets , junk food and fatty foods occupied the highest ranked reason selected by 19.8% of the students .\nthe students also admitted that most of them ate what they were accustomed to eating .\nthey ate what they liked to eat , and the decision about what to eat was made because of the taste of the food without regard for any health consequence or negative health outcomes .\nthe number two reason for not eating healthy was that students believed that the food they were served in the school s cafeteria was of poor quality : 15.7% of the students responses supported this view .\nthe number three reason given for not eating more nutritious foods was family background , family customs and family heritage : 14.1% of the students acknowledged that they ate the way they did simply because they inherited those patterns from their family .\nin other words , they ate what their parents could afford to buy and prepare for meals .\nmany of them asserted that they were simply not accustomed to eating nutritious foods daily .\nthese students stated that they buy the types of food they want , and , in some instances , they want the fast foods more than anything else .\nthe students placed fast food restaurants as number five among the reasons why they found it difficult to practice positive eating habits .\nranked number six as a factor that inhibits them from healthy eating habits is the easy access to junk foods and other unhealthy foods : 6.6% of them blamed the easy accessibility of junk foods as a perpetrator of the unhealthy dietary choices and practices .\nanother 6.6% of the students cited lack of care and guidance from responsible adults as a factor that prevents them from practicing good dietary habits .\nthese students admitted that pressure from videos and corporate advertisements helped to steer them in the wrong direction in reference to the choices they make .\nthe negative influences perpetrated by famous actors , sports personalities and performers usually project the wrong messages and oftentimes influence many students to act spontaneously and without proper judgment . as a result ,\nmany of them make the decision to eat daily at fast food restaurants , where they often consume an over abundance of unhealthy meals . several students reported that there was no one in their life to motivate them with positive messages or inspiration , and not many people cared enough .\nthe number eight ranked reason for students not practicing positive eating habits was the presence of snack machines at school , laden with junk food .\nabout 5.0% of the students cited this as a possible obstacle to good eating practices .\napproximately 19.8% of the students did not express an opinion about what is keeping them and other students from eating better ( more nutritious foods ) .\nthe students were also asked what do you think is keeping you or other students from taking part in sufficient exercise ( daily physical activity ) ? \nthe number one reason offered by students for inadequate participation in physical activity is laziness .\nsome students insisted that there are many students who believe that they are too cute to dress in workout gear , and do not want to sweat during physical activity .\napproximately 38.9% of the students perceived that as the main reason why many students do not participate in activities today .\nthe next reason cited by 14.3% of the students was that they preferred to hang out with friends rather than participate in physical activity . since it is not required daily\nmany of them would prefer to attend parties , talk on the telephone , ride around in cars or watch television , rather than participate in physical activity . and , besides , as some of them insisted , the school has not been helpful in encouraging them to look at the positive benefits of daily exercising .\nthe third ranked reason was that they simply have no desire to take part in physical activity ( see figure 2 ) .\nabout 6.3% of the students cited self esteem issues and the feeling of embarrassment as a major contributing factor .\nthe number five ranked reason for non - participation was the volume of homework assignments they have .\nthese students felt that they just do not have the time to participate in physical activity .\napproximately 3.2% of the students explained that their inadequate participation is due to a lack of adequate mixture of games available at school .\nhealth problems were cited by 2.4% of the students as obstacles , and 1.6% of them indicated that disagreements with the gym teacher resulted in their non - participation .\na small number of students believe that being fat or overweight was a contributing factor to their failure to participate in physical activity . there were approximately 19.0% of the students who had no opinion about what was keeping them and other students from taking part in sufficient exercise ( daily physical activity ) .\nthe students also responded to the question what do you think is needed to help students to start eating better and exercising more ?\n the number one suggestion given by students for improving their quality of life was that the school should provide better and more nutritious cafeteria food ( see figure 3 ) .\nthis was equaled in number by the need for guidance by school personnel and parents in the area of healthy eating practices .\nthey felt that the adults should show more interest and concern , and do more to provide adequate instruction and direction , possibly implementing new programs or activities and increased time in health class to address these important issues .\nthey also believed that the parents have a major responsibility to lead the way by providing positive alternatives .\nthis was followed by the need for more encouragement and motivation , as expressed by 14.1% of the students .\nabout 11.3% of the students felt that the school should increase the volume of physical activity and exercise offered to students daily .\nnumber five among the students suggestions was the recommendation that the school make exercise mandatory for students .\nthe students felt that , as incentives , school officials should use prizes , grades or money to encourage students to participate .\nanother 6.3% of the students suggested that school should make exercise and nutrition programs more fun to encourage students to participate .\nsome students concluded that increased conversation about the topic would lead to heightened motivation among students to participate in activities that are offered in their health and physical education classes .\nabout 4.2% of the students believed that parents and teachers do not care enough to provide them with adequate guidance and opportunity .\nthe students felt that the school needs to implement a healthy life program within its curriculum .\napproximately 4.2% of the students indicated that the students themselves should eliminate junk food and fast foods from their daily lunch menus .\nanother group of students suggested that more positive advertising of nutritious foods should be encouraged and should be a major part of the plan to improve the students quality of life .\nstudents felt that they should be constantly apprised of the dangers of negative practices regarding poor eating practices and inadequate physical activity .\nthis would facilitate their change to healthier daily practices which could possibly add years to their lives .\napproximately 11.3% of the students said they did not know the answer and could not present any suggestions .\nthe major limitation of this study was the fact that only 42% of the total number of students eligible to participate in the study provided surveys that could be analyzed .\n. however , their responses are valuable enough to shed some light on obstacles to good health and possible solutions to improve the quality of life and develop ways of helping them to eliminate negative practices and reduce risk factors .\nthe major limitation of this study was the fact that only 42% of the total number of students eligible to participate in the study provided surveys that could be analyzed .\n. however , their responses are valuable enough to shed some light on obstacles to good health and possible solutions to improve the quality of life and develop ways of helping them to eliminate negative practices and reduce risk factors .\nthe interpretation of the students responses to these critical health issues identifies certain urgent needs that could and should be addressed by the academic institutions .\nmany students understand that there may be negative consequences resulting from the daily choices that they make .\nit is clear that culture and family customs have a great influence on the direction students take in their dietary practices , as well as their involvement in physical activity .\nthe convenience and easy accessibility of low nutritious foods is also seen as a contributing factor , as are the negative influences that are presented through advertising of non - nutritious foods .\nit is evident that adequate support and guidance from adults are not available often enough to facilitate the kind of learning and training that could ensure that students are afforded the opportunity to acquire knowledge to help them make positive responsible choices and decisions .\nso children have little desire to take the initiative to make improvements in their daily practices .\nthe students suggested that modifying the schools curriculum to address student risk behaviors should become an embedded characteristic of their educational systems .\nthe current absence of learning strategies to adequately address and educate students about the pitfalls of negative dietary and physical behaviors is a major shortcoming of the school s education system .\nrecommendations for future studies should involve examining the responses of students enrolled in predominantly white institutions with those of the predominantly african american canton public school district . studies could also be designed to compare the responses of students from urban schools and rural schools to determine what their perceptions and recommendations are concerning risk factors and ways of reducing them .", "answer": "this study was designed to assess students perceptions of the obstacles to positive dietary practices and increased physical activity and to solicit the students recommendations for addressing and possibly reducing the negative practices that are associated with the rise in obesity and the development of cardiovascular diseases . \n data for the study were obtained from the administration of the 2005 project health high school survey ( phhss ) which measured the students perceptions regarding obstacles to eating more nutritious , healthier foods and obstacles to participating in daily physical activity . \n the reasons for students lack of interest in practicing more life - healthy behaviors are ranked and recorded . \n some of the students indicated that they usually ate what they liked to eat , and the decision about what to eat was made because of the taste of the food without regard for any health consequence or negative health outcomes . \n finding ways to reach these students at their young ages is the key to successfully combating the high prevalence of obesity and the development of other chronic diseases in childhood , as well as in adulthood .", "id": 729} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npmds is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man .\nit is characterized by the persistence of the uterus , fallopian tubes and upper vagina in otherwise normally virilized boys . despite the normal male genotype ( 46 xy ) and the subsequent normal development of fetal testes , mllerian structures do not regress either due to absence of mllerian inhibiting substance ( mis ) or lack of response to it .\nthe persistence of a large uterus - like paramesonephric duct in a man is in itself clinically unusual , but when it forms a part of the contents of a hernial sac , it must be considered a rarity .\nwe report the case of a 70 year old man with unilateral cryptorchidism on the right side and left obstructed inguinal hernia containing uterus and fallopian tube ( that is , hernia uteri inguinalis ; type i male form of pmds ) coincidentally detected during an operation for an obstructed left inguinal hernia with right cryptorchidism .\na 70 year old man presented to our hospital with a painful left - sided inguinal swelling of one day duration . the patient gave history of asymptomatic left inguinal swelling from past 20 years and absence of the right testis since birth .\nhe had been married for fifty years and was having 4 children , the youngest one being 38 year old female .\ngeneral physical examination revealed a man of sub - average built with well developed secondary sexual characters . his urethra and penis\nwere fully developed with a poorly developed right hemi - scrotum and no palpable right testis in the scrotum or inguinal canal .\nthere was a non - reducible , tender swelling measuring approximately 10 8 cm in the left inguinal region with absent cough impulse .\nexploration of the inguinal canal revealed an indirect inguinal hernia containing a globular structure resembling uterus , fallopian tubes with an atrophic right testis embedded in the broad ligament and attached to pelvis with a thick fibrous band [ figs . 1 and 2 ] .\ntotal excision of the uterus with fallopian tubes and atrophic right testis was performed and the operation was completed with left inguinal hernioplasty [ figs . 3 and 4 ] .\ngrossly , the specimens removed were identified as a uterus with patent endometrial and endocervical linings and two fallopian tubes .\nthe right testis measuring 2 1 1 cm , was atrophic and embedded in the right broad ligament .\nthe specimen was sent for histopathological examination which revealed uterine muscular tissue with its cavity lined by endometrial tissue and congested fallopian tubes .\nmale pseudo - hermaphroditism is a condition in which the gonads are testes but the internal genitalia are not completely virilized .\npmds is a rare form of internal male pseudo - hermaphroditism in which mullerian duct derivatives are seen in men .\nthe exact cause of pmds is not known , however it is thought to result from a defect of the synthesis or release of mif , or from defects in the mif receptor .\ndefects in the mif gene lead to the persistence of a uterus and fallopian tube in males .\nit is likely that remnant mullerian structures lead to cryptorchidism by hindering the normal testicular descent mechanism .\npatients with pmds usually have normal development of external genitalia and secondary sexual characteristics . the typical patient with pmds\nhas unilateral or bilateral cryptorchidism and is assigned to the male sex at birth without hesitation , as they have normal male genotypes and phenotypes .\nthe male form is encountered in 8090% of cases , characterized by unilateral cryptorchidism with contralateral inguinal hernia , and can be one of the two types : the first type is hernia uteri inguinalis , which is characterized by one descended testis and herniation of the ipsilateral corner of uterus and fallopian tube into the inguinal canal .\nthe second type is crossed testicular ectopia , which is characterized by herniation of both testes and the entire uterus with both fallopian tubes .\nclinically , the persistence of a uterus and fallopian tubes leads to either cryptorchidism or inguinal hernia depending on whether or not mullerian derivatives can be mobilized during testicular descent .\nif the uterus and fallopian tube are mobile , they may descend into the inguinal canal during testicular descent .\npmds is usually coincidently detected during surgical operation , as in our patient 's case .\nhowever pre - operative ultrasonography , computerized tomography and mri allow possible pre - operative diagnosis .\nan element of deciding on intervention is largely based on reducing risk of malignancy , while maintaining maximum reproductive function . in pmds patients with undescended testes ,\nthe rate of testicular cancer is about 12% which is comparable to the rate seen in undescended testes not associated with pmds .\nseveral authors have asserted that the mullerian structures should not be removed as there is minimal risk associated with their retention , and excision of the mullerian structures risks damaging primary blood supply to the pmds testis via the internal spermatic and deferential arteries .\nhowever most recent reports have demonstrated rare malignancies including adenocarcinomas of the mullerian duct associated with retained mullerian structures .\npmds is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man .\nsince patients are phenotypically male , the diagnosis is usually not suspected until surgery is performed for cryptorchidism or hernia repair .\nhernia uteri inguinalis is type i of the male form of pmds , characterized by one descended testis and the herniation of the ipsilateral corner of the uterus and fallopian tube into the inguinal canal . in order to prevent further complications such as infertility and malignant change\n, the surgeon should be aware of pmds while dealing with patients who present with unilateral or bilateral cryptorchidism . in summary , in cases of unilateral or bilateral cryptorchidism associated with hernia , as in our patient 's case ,\na written informed consent was obtained from the patient for publication of the case report and various images which may be used with the same .\nthe patient being a major gave a written consent of the same after assuring him that name and hospital mrd no of the patient will not appear in the case report .\nall the authors have contributed either as being part of surgical and anaesthesia team or helping in the photography , paper writing , submission etc . afak yusuf sherwani , abdul qayoom shah , abdul majeed wani , farooq ahmad sofi and ashfaq amin wani were in the surgical team .\nbashir a chalkoo , bashir a khan and ab hamid sherwani in the anaesthesia team .\nwasim lone , mehmood a sheikh and raj reshi sharma did photography and paper writing .", "answer": "introductionpersistent mullerian duct syndrome is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man ; only a few cases have been reported in the worldwide literature . \n a great variety of organs have been found in indirect inguinal hernial sacs.presentation of casewe report a case of 70 year old man , father of 4 children with unilateral cryptorchidism on the right side and left - sided obstructed inguinal hernia containing uterus and fallopian tube ( that is , hernia uteri inguinalis ; type i male form of persistent mullerian duct syndrome ) coincidentally detected during an operation for an obstructed left inguinal hernia.discussionpmds is usually coincidently detected during surgical operation , as was in our case . \n however pre - operative ultrasonography , computerized tomography and mri allow possible pre - operative diagnosis.3conclusionin cases of unilateral or bilateral cryptorchidism associated with hernia , as in our patient 's case , the possibility of pmds should be kept in mind .", "id": 730} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA visible-light mediated three-component radical process using dithiocarbamate anion catalysis\n\nPaper sections:\nIntroduction\nMulticomponent reactions (MCRs) are important in synthetic chemistry because they allow the rapid construction of complex molecules from simple substrates and in a single step. 1 While chemists have predominantly developed methods based on polar pathways, radical reactivity provides a powerful alternative. 2,3 However, methods to initiate radical MCRs have traditionally required unstable initiators or stoichiometric oxidants or reductants (Fig. 1a). 4 These relatively harsh conditions for generating open-shell intermediates (high temperatures, toxic reagents or strong redox-active reagents) signi\ue103cantly affect the selectivity and the functional group tolerance of the overall radical cascade processes. Recently, the \ue103eld of photoredox catalysis 5 has overcome some of these limitations, offering effective tools to trigger radical MCRs under mild conditions while avoiding the need for stoichiometric metals or harsh atom abstractors. 6 However, this radical generation strategy mainly activates substrates via single-electron transfer (SET) pathways, thus relying on their redox properties. 7 This intrinsic feature poses a voltage-gated limit to the generality of the radical precursors that can be used.
In this context, our laboratory recently reported a unique photochemical catalytic strategy, which harnesses different physical properties of the substrates to generate radicals (Fig. 1b). 8 Speci\ue103cally, we designed the readily available and air- and moisture-stable dithiocarbamate (DTC) 9 anion catalyst A, which is adorned with an indole chromophoric unit. This organic catalyst is nucleophilic enough 10 to activate alkyl electrophiles by displacing a variety of leaving groups via an S N 2 pathway. The resulting photon-absorbing intermediates I afford radicals upon excitation by visible light and homolytic cleavage of the weak C-S bond. 11 This catalytic S N 2-based strategy, which is not reliant on the redox properties of the radical precursor, grants access to open-shell intermediates from substrates that would be incompatible with or inert to classical radicalgenerating strategies, including photoredox catalysis.
Here, we demonstrate how this photochemical strategy can be translated into the realm of radical MCRs to design cascades that would be difficult to implement with other methods. Speci\ue103cally, we report a three-component reaction mediated by the DTC potassium salt catalyst A that uses difficult-to-reduce alkyl chlorides 1 as radical precursors and couples them with readily available maleimides 2 and heteroaromatic fragments 3 (Fig. 1c). This carbo-difunctionalization of maleimides 12 combines two sequential intermolecular radical-based bondforming processes to afford complex products 4 containing a succinimide moiety. This structural element is found in numerous biologically active molecules. 13 Importantly, the method's redox neutral conditions and high functional group tolerance allow us to easily adorn products 4 with a variety of biologically relevant N-heterocycles, 14 which would not be compatible with strong redox-active reagents.
\n\nMechanistic plan\nThe speci\ue103c mechanistic details of our proposed photochemical radical MCR are outlined in Fig. 2. We envisioned a catalytic cycle where the DTC catalyst A would activate alkyl chlorides 1 upon S N 2 attack. 10 The resulting intermediate I possesses a weak C-S bond, which would be cleaved by low-energy photons (blue LEDs) to generate the target carbon radical II and the dithiocarbonyl radical III. 11 The nucleophilic open-shell intermediate II would initiate the radical cascade upon interception from maleimide 2, which forges a new C-C bond. The emerging electrophilic radical IV would in turn participate in a second trapping event with an electron-rich heteroaromatic compound, affording the open-shell intermediate V. This crucial intermediate would act as a reductant to turn over catalyst A upon SET reduction of the dithiocarbonyl radical III. 15 Overall, this net redox-neutral transformation would deliver the functionalized cascade product 4. 8
\n\nResults and discussion\nTo test the feasibility of our strategy, we selected the commercially available N-(chloromethyl)phthalimide 1a as precursor of a nucleophilic radical, N-methylmaleimide 2a as the radical trap, and N-methylpyrrole 3a as the terminal electron-rich heteroaromatic trap (Table 1). The experiments were conducted at 60 C in DCE using blue LEDs emitting at 465 nm, 20 mol% of the DTC catalyst A and a large excess of 3a. These conditions furnished the cascade product trans-4a in good chemical yield and with excellent diastereoselectivity (dr > 20 : 1, entry 1). Under these conditions, we did not observe any byproduct arising from either a pyrrole alkylation radical path with 1a or a polar addition of 3a to maleimide 2a. Variations of the initial conditions, including a lower catalyst amount and temperature (entries 3 and 4), led to poorer results. Control experiments established that both catalyst A and light are necessary to trigger the three-component radical process (entries 5 and 6), thus excluding an alternative polar pathway for the formation of 4a. a Reactions performed on a 0.1 mmol scale at 60 C for 20 h using 0.2 mL of solvent under illumination by blue LED strip (l max \u00bc 465 nm) and using catalyst A (20 mol%), 1.5 equiv. of 1a, and 10 equiv. of 3a. b Yield of 4a determined by 1 H NMR analysis of the crude mixture using trichloroethylene as the internal standard; value in parenthesis refers to the yield of isolated 4a. DCE: 1,2-dichloroethane; AcOEt: ethyl acetate; NPhth: phthalimide.
Interestingly, no product formation was observed when replacing catalyst A with the strongly reducing fac-Ir(ppy) 3 photoredox catalyst (E 1/2 Ir(IV)/Ir(III*) \u00bc \u00c01.73 vs. SCE), 16 which highlights the inability of photoredox catalysis to trigger the radical MCR process (entry 7). 17 Using the optimized conditions described in Table 1, entry 1, we turned our attention to exploring the generality of the photoinduced radical cascade process (Fig. 3). The method is amenable to synthetically useful purposes, since a high efficiency was maintained when running the reaction on a 5 mmol scale. This experiment did not require any modi\ue103cation of the standard experimental set-up (see ESI \u2020 for details), and it afforded product 4a in good yield and with complete diastereoselectivity (0.91 g, 52% yield, >20 : 1 dr). We then explored the scope of the radical precursors 1 could be activated by the DTC catalyst A. Our approach displayed a high degree of tolerance towards N-heterocycles, as the cascade products 4 could be readily adorned with triazole (4b), pyrazole (4c), isoxazole (4d), benzothiazole (4e), and thiazole (4f) scaffolds. Other heterocyclic moieties, such as furan (4g) and thiophene (4h), were also tolerated. These common motifs are typically found in drug molecules. However, they generally represent a signi\ue103cant tolerability challenge for synthetic methods. 14a The corresponding MCR products 4 were obtained with good yields and complete diastereoselectivity. Importantly, the reduction potentials of the heterocyclic-containing substrates 1, evaluated by cyclic voltammetry, are sufficiently negative (E red < \u00c02.0 V vs. Ag/AgCl, see ESI \u2020) to remain out of reach of most commonly used photoredox catalysts. 5 Therefore, SET-based reduction methods to generate the target radicals and trigger this MCR process would require strong reductants, greatly limiting functional group compatibility.
Fig. 3 Reaction scope: reactions performed on 0.5 mmol scale using 1.5 equiv. of 1, 10 equiv. of 3, and 1.0 mL of 1,2-dichloroethane; yields of products 4 refer to isolated material after purification. a NMR yield determined using 1,1,2-trichloroethylene as the internal standard. b The corresponding bromides 1 were used as radical precursors. c 3 equiv. of 1; NPhth: phthalimide.
Benzylic radical precursors, bearing both electron-rich and electron-poor aryl substituents, were also competent substrates, affording the complex products in moderate to high chemical yields (4i-4s, 28-72% yield). Reactive functional groups, including an aryl iodide (4m), a boron ester (4o), an amide (4p), and a free alcohol (4q), were all tolerated activated exclusively at the desired benzylic position. Regarding the diastereoselectivity, full control was achieved with electron-rich benzyl systems, while the presence of electron-withdrawing moieties affected the relative stereocontrol (4i-k, 4n). In addition, prenyl chloride, which delivered an allylic radical upon activation, could be successfully used in the MCR (product 4t), albeit with reduced diastereoselectivity. The N-protecting group of the maleimide 2 was found to be important for stereocontrol, as unprotected maleimide resulted in low diastereoselectivity (product 4u). Substrates 2 bearing more encumbered protecting groups were well tolerated (adducts 4v, 4w), and thiophene was found to be an alternative terminal radical trap (4x and 4y). A complete list of moderately successful and unsuccessful substrates for this radical MCR strategy is reported in Section D, Fig. S5 of the ESI. \u2020 To showcase the system's synthetic utility, we used this strategy to prepare highly functionalized pyrroles, which are relevant motifs found in natural products, pharmaceuticals, and materials. 18 Speci\ue103cally, we envisioned an assembly line protocol that combines two sequential radical processes, governed by the DTC catalyst A and visible light, to achieve a 2,5difunctionalization of a commercial pyrrole building block (Scheme 1a). First, the photochemical activation of chloroacetonitrile 5 by A generates an electrophilic radical, which is readily intercepted by N-methyl pyrrole to deliver the functionalized intermediate 6 in 92% yield. 8 By exploiting the residual nucleophilic character of C5, the pyrrole 6 was then used in the MCR process with N-(chloromethyl)phthalimide 1a and Nmethylmaleimide 2a to rapidly assemble the difunctionalized pyrrole 7 from commercially available substrates.
Finally, we demonstrated that the succinimide moiety within the MCR products 4 can be readily transformed into a pyrrolidine, which is a synthetically and biologically relevant framework. 19 As highlighted in Scheme 1b, the reduction of adduct 4w with LiAlH 4 affords the corresponding trans-3,4-disubstituted pyrrolidine 8. This transformation further testi\ue103es to the potential of this MCR strategy to cover biologically relevant chemical space.
\n\nConclusions\nWe have developed a visible-light-mediated three-component radical strategy, which couples readily available alkyl chlorides, maleimides, and heteroaromatic fragments to rapidly generate complex products. The MCR is founded upon an S N 2based radical-generation strategy, which is not reliant on the redox properties of the radical precursors and therefore overcomes the limitations of photoredox chemistry. The redox neutral conditions of this process make it tolerant of redoxsensitive substrates and allow the installation of multiple biologically relevant heterocycles within the products. These \ue103ndings, along with the experimental simplicity and the low cost of the catalyst, suggest that this method can inspire the design of other voltage-independent radical applications and would be amenable to interrogating new chemical space in medicinal chemistry.
\n\nConflicts of interest\nThere are no con\ue104icts to declare.
", "answer": "We report a photoinduced three-component radical process, which couples readily available alkyl chlorides, maleimides, and heteroaromatic fragments to rapidly generate complex chiral products with high diastereocontrol. This method generates radicals via an S N 2-based photochemical catalytic mechanism, which is not reliant on the redox properties of the precursors. It therefore grants access to open-shell intermediates from substrates that would be incompatible with or inert to classical radicalgenerating strategies. The redox-neutral conditions of this process make it tolerant of redox-sensitive substrates and allow the installation of multiple biologically relevant heterocycles within the cascade products.", "id": 731} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nChiral Br\\xc3\\xb8nsted Acid from a Cationic Gold(I) Complex: Catalytic Enantioselective Protonation of Silyl Enol Ethers of Ketones\n\nPaper sections:\n\nOver the past decade gold catalysis has attracted significant attention from synthetic community.1 More recently, notable progress has been made in asymmetric catalysis using homogenous gold(I) complexes. In general, enantioselective reactions have relied on the ability of cationic gold(I) complex \u03c0-donor ligands such as alkynes, allenes, and alkenes and activate them toward nucleophilic attack.2\u20134 In contrast, similar \u03c3-complexes of cationic gold complexes with \u03c3-donor ligands have been little explored in asymmetric catalysis, although there have been several reports of reactivity differences in gold catalysis in the presence of protic additives.5 Very recently, we found that alcoholic additive have a dramatic effect on the regio- and enantioselectivity in gold-catalyzed hydroamination of 1,3-dienes.6 For example, in the absence of alcohol, 1,2-addition products were obtained as exclusive products with very poor enantioselectivity, whereas in the presence of an alcohol additive 1,4-addition products were obtained in good yields and high enantioselectivity (eq 1).
\n(1)\n
We hypothesized that in the absence of alcohol, the cationic gold(I) directly activates the 1,3-diene towards nucleophilic attack leading to the 1,2-addition products. On the other hand, in the presence of alcohol, cationic gold(I) forms \u03c3-complex with alcohol to generate chiral Br\u00f8nsted acid activated by complexation with gold; a so called, Lewis acid activated Br\u00f8nsted acid (LBA).7 Based on these observations, we envisioned that a new chiral Br\u00f8nsted acid could be generated by complexation of alcohol with cationic gold, significantly enhancing the acidity of the original alcohol. Herein we describe the development of a chiral LBA derived from cationic gold complex and its application to enantioselective protonation reaction of silyl enol ethers of ketones.8\u201311
We began our investigation by examining the protonation reaction of silyl enol ether 4a, catalyzed by 3 mol% (R)-DTBM-SEGPHOS(AuCl)2 activated by 3 mol% AgBF4, in isopropanol as a solvent. Under these conditions, the desired protonation product 5a was obtained in quantitative yield and 87% ee (Table 1, entry 1). Encouraged by this initial result, we examined other chiral diphosphine(bis)gold complexes as catalysts for the enantioselective protonation reaction (entries 1\u20136). Among the gold(I) complexes tested, the (R)-BINAP-derived complex proved to generate the most selective catalyst for the asymmetric protonation reaction (entry 5).
With BINAP as the diphosphine ligand on gold, we next examined the effect of counterions on the protonation reaction (entries 4, 7\u201311). Generation of the cationic gold(I) complex proved essential for the protonation reaction, as no protonation was observed without AgBF4 (entry 12), or when a more coordinating counterion was used (entry 7). On the other hand, reactive catalysts were generated from non-coordinating anions (entries 4, 8\u201311), with tetrafluoroborate providing the protonation adduct with highest enantioselectvity. Furthermore, the catalyst derived from the monocationic gold(I) complex proved more selective than the one from dicationic gold complex (entries 5 and 13). We also investigated the possibility of protonation catalyzed by a Br\u00f8nsted acid derived from AgBF4\u00b7BINAP complex; however, this silver-based Br\u00f8nsted acid was not reactive enough to protonate silyl enol ether 4a (entry 14).12 Finally, the enantioselectivity could be further increased by changing the solvent from isopropanol to ethanol (entry 15).13
With these optimized conditions, we first investigated the scope of the gold-catalyzed enantioselective protonation reaction of silyl enol ethers of cyclic ketones (Table 2). Various silyl enol ethers from 2-aryl cyclic ketones could be employed in the enantioselective protonation reaction and the corresponding ketones were obtained with excellent yields and high enantioselectivities (entries 1\u20135). The cationic gold(I)-derived LBA could be further applied to the protonation reaction of silyl enol ethers of 2-alkyl cyclic ketones (entries 6\u20137). Tetralone and indanone analogs bearing a methyl group at the 2-position were obtained in quantitative yields and excellent enantioselectivity. It is noteworthy that the ring size of cyclic ketones had little effect on reactivity and high levels of enantioselectivity were obtained regardless of ring size (entries 1 vs 5, 6 vs 7).
Although several examples of Br\u00f8nsted acid-catalyzed enantioselective protonation reactions of silyl enol ethers of cyclic ketones have been reported,9\u201311 to the best of our knowledge, there have been no reports of Br\u00f8nsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic ketones.14,15 Therefore, we next examined the use of our gold(I)-based catalytic system in the enantioselective protonation of these more challenging substrates. The first anticipated challenge with acyclic substrates is the stereochemistry of starting silyl enol ethers. In contrast to cyclic ketones having only one isomer of silyl enol ethers, acyclic ketones can generate both (E) and (Z) silyl enol ethers. Since the transition states for the protonation of the diastereomeric silyl enol ether are different, we anticipated that it might be important to diastereoselectively generate the silyl enol ethers.8e Furthermore, the acyclic substrates generally have more conformational flexibility than the corresponding cyclic ones, which can also lead to lower asymmetric induction.
With these challenges in mind, we examined our LBA-catalyzed asymmetric protonation reactions of silyl enol ethers of acyclic substrates (Table 3). First, we attempted to synthesize stereochemically pure silyl enol ether 6a of 2-phenyl propiophenone. After several unsuccessful attempts to obtain stereochemically pure silyl enol ether of 2-phenyl propiophenone,16 we decided to apply a mixture of (E) and (Z) silyl enol ethers to enantioselective protonation reaction under the standard condition developed for protonation reaction of cyclic substrates. To our surprise, the protonation product was obtained in nearly quantitative yield and 92 % ee despite a 2:1 isomeric ratio of the silyl enol ether substrate (entry 1, Table 3).
With this rather unexpected result in hand, we moved our attention to other acyclic substrates under those reaction conditions. Several other silyl enol ethers from 2-aryl propiophenones were prepared were prepared as a mixture of E/Z isomers. Protonation products, however, were obtained in excellent yields and high enantioselectivities regardless of the ratio of E/Z in the starting silyl enol ethers (entries 2\u20138). Electronic effects had little impact on enantioselectivity (entries 1\u20134), although electron-withdrawing substituents required somewhat longer reaction times (entry 4). Acyclic ketones bearing bulky aryl groups at the alpha-position, such as ortho-substituted aryl group, are tolerated, albeit with slightly lower enantioselectivity (entries 6\u20138). We further examined the effect of substituents on the aromatic ring of 2-phenyl propiophenene (entries 1, 9\u201311). Substituents on the phenyl ring have little effect on enantioselectivity (entries 1,9\u201310), although the silyl enol ether with an electron-withdrawing substituents decreased reacted more slowly in the protonation reaction (entry 11). Furthermore, alkyl substituted silyl enol ether 6l could also be employed in the gold-catalyzed protonation reaction with only slightly lower enantioselectivity (entry 12). The catalyst system was also effective for the protonation of the silyl enol ether of 2-phenyl butyrophenone (6m), providing the desired ketone in 91% yield and 85% ee (entry 13). However, the silyl enol ether possessing two alkyl groups at the \u03b1-position provided the protonation product in poor enantioselectivity (entry 14).17
Several experiments were conducted in order to gain insight into the reaction mechanism. First, we tested the possibility that the reaction proceeded by protonation of a gold enolate18,19 generated transmetallation of the silyl enol ether; however, silyl enol ether 6a remained intact and we could not detect any gold enolate formation on treatment the cationic gold complex in the absence of alcohol. A second possible scenario is selective protonation of a rapidly equilibrating mixture of silyl enol ether isomers, in which the isomerization is catalyzed by either protonation or the cationic gold complex.20 However, we did not observe any isomerization between silyl enol ethers by either LBA or the cationic gold complex and the ratio of E/Z isomers did not remain constant during the protonation reaction (Figure 1). The third scenario is that the gold-derived LBA discriminates both isomers and approaches both silyl enol ethers from the same prochiral face, which results in very high enantioselectivity regardless of a ratio of (E) and (Z) silyl enol ethers. This scenario is consistent with the observation that the enantioselectivity of the reaction remains constant, despite the changing ratio of olefin isomers (Figure 1). Similarly, protonation of the silyl enol ether of 2-phenyl propiophenone with different E/Z ratios, produced ketone 7a with comparable the yields and enantioselectivities (eq 2).
\n(2)\n
In conclusion, we have developed the first gold-catalyzed enantioselective protonation reaction. The chiral Br\u00f8nsted acids derived from cationic gold-complexes and an alcohol were applied to enantioselective protonation reaction of silyl enol ethers of ketones. Various silyl enol ethers from cyclic ketones could be applied to this catalytic system and the desired protonation products were obtained in excellent yields and high enantioselectivities. Furthermore, the catalytic system could be extended to the first enantioselective protonation reactions of silyl enol ethers of acyclic ketones. The silyl enol ethers of acyclic ketones afforded the corresponding ketones in high enantioselectivities even with a mixture of (E) and (Z) isomers of silyl enol ethers. Mechanistic studies suggest that a gold-derived LBA selectively protonates silyl enol ethers from the same prochiral face regardless of their stereochemistry.
", "answer": "A chiral Br\\xc3\\xb8nsted acid has been developed from cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities including cyclic ketones bearing aliphatic substrates at the \\xce\\xb1-position. Furthermore, the application of this Br\\xc3\\xb8nsted acid was extended to the first Br\\xc3\\xb8nsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.", "id": 732} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the last two decades , a large research effort has been devoted to quantum dots ( qds ) , the quantum wires , qd chains , nanoholes and pits [ 1 - 8 ] due to their modified density of states , fascinating optoelectronic properties and device applications for lasers , photodetectors and other electronic devices . among quantum dots , pits and wires fabrication techniques , the self - organized stranski \nkrastanow method is an important one by which dislocation - free dots , elongated islands and wires can be produced . indeed , above a certain critical thickness , the growth mode switches from the conventional layer - by - layer ( i.e. , two - dimensional , 2d ) to a 3d growth mode due to the accumulation of the elastic energy in the strained layer that , first , partially relaxes by spontaneously nucleating small islands of strained material and , later , by creating misfit dislocations .\nthe elastic strain caused by lattice mismatch can also be relaxed by the formation of undulations , pits and their combination [ 5 - 8 ] .\ndepending on the growth conditions , the elastic strain can be relaxed by the formation of either quantum wires and quantum dots , or even unique island \nextensive experimental results suggest that surface morphologies are relying on growth conditions and matrix materials . on the basis of an atomistic model\n, it is shown that the energy change due to the step formation is negative or positive depending upon the sign of the misfit\n. the step formation energy can even be negative for compressive misfit stress in the heterolayer , while it is definitely positive for tensile misfit stress .\nthis conclusion is in contrast to the classical model where the step energy is always positive and independent of the sign of the misfit .\nthe step formation energy influences the critical thickness and the energy barrier for dislocation nucleation . using a simple atomistic simulation\n, it is shown that the critical thickness depends upon the sign of the misfit .\nfor example , it changes from 4 nm for ge films on si(100 ) substrates to 6 nm for si films on ge(100 ) substrates having the same misfit .\nthe investigations of the surface morphology evolution of strained inas / gaas films at different growth conditions demonstrated that there are at least three different strain relaxation mechanisms for the same material system .\nthat is , depending on the growth conditions , the elastic strain can be relaxed by the formation of either quantum wires or quantum dots , or even unique island pit pairs .\n. both the island height and the pit depth can be much greater than the average layer thickness .\nthis suggests that considerable mass transport from substrate into the islands is taking place during the growth .\nhowever , during heteroepitaxy , when the layer becomes sufficiently thick , the pits are eventually filled up either by the lateral overgrowth or by the expanding islands , forming nearly pure island morphology at the surface .\nthe detailed analysis of the surface dynamics during phase transitions of gaas(100 ) and unusual role of the substrate at droplet - induced gaas / algaas qd pairs growth also confirm this assumption . from the industrial point of view , the narrow band gap iii \nv semiconductor materials like inas , gasb , insb and their ternary and quaternary alloys are particularly interesting and useful since they are potentially promising to access mid - infrared and far infrared wavelength regions .\nthese materials would provide the next generation of leds , lasers and photodiodes for applications such as infrared gas sensors , for molecular spectroscopy , thermal imaging , photovoltaic ( pv ) and thermo - photovoltaic cells ( tpv ) .\nthe application of the inassbp and other similar quaternary materials opens up interesting physical and technological prospects for the dirigible growth of qds , the pits and dots pits cooperative systems .\nindependent variations of the third and fourth components provide corresponding sign of the misfit ; i.e. , providing the tensile or compressive misfit stress .\nat the first case , elastic strain will be relaxed by the formation of qds , but at the second one by the pits . in this article , an example of inassbp quaternary qds , the pits and dots pits cooperative structure growth on inas(100 ) substrates by lpe , as well as the interaction and surface morphology of the dots pits combinations are presented and investigated .\nthe samples are grown by lpe using a slide - boat crucible . to ensure a high purity of the epitaxial layers ,\nthe inas(100 ) substrates have a 11 mm diameter are undoped , with a background electron concentration of n = 2 10 cm .\nthe inas0,742 sb0,08 p0,178 quaternary alloy used here as basis composite is conveniently lattice - matched to inas .\nthe lpe growth solution components undoped inas , undoped inp and sb ( 6 n ) are solved in a in ( 7 n ) solution that has been first homogenized for 1 h at t = 580 c and then 3 h at the initial growth temperature of t = 550 c to equilibrate the system thermodynamically . to expect the strain - induced qds and pits formation , the undoped and supersaturated by antimony and phosphorus liquid phase was used to provide a different sign of lattice mismatch up to 4% between the inas substrate and inassbp epilayer . to initiate the growth of qds and pits ,\nan oversaturation of the liquid phase is developed by decreasing the initial growth temperature up to 2 c at the slower ramp rate .\nthe high - resolution scanning electron microscope ( sem - edxa fei nova 600dual beam ) is used to study the strain - induced inassbp qds \n1 ) that the pits ( large and small ) like the islands primarily formed into truncated reverse pyramids . the edxa measurements shown that , at first , either islands or pits edges have a quaternary composition and that on average , they are enriched by antimony and by phosphorus , respectively . in our inassbp quaternary experimental system , the nucleation mechanism of qds and the exposure of wetting layer ( and inas substrate ) at pits are quite interesting , but very complicated for explanation result . from a physical perspective\n, we have assumed that simultaneous nucleation of the islands and pits are occurring due to variable curvature ( the tensile or compressive local perturbations ) of the wetting layer .\nwe suggest that at the perturbed sites , the wetting layer surface is strained , and the depositing material will prefer not to remain at these sites , but rather diffuse away .\nafter that occurs , the strain relaxation is performed at the adatoms ( sb and p ) surface diffusion in opposite directions , leaving behind the islands and the pits on the surface . in this scenario , corners or edges of the pits and islands\nare the most preferred sites to attach newly deposited materials , because at these regions , the strain energy is most relieved .\nthe islands ( or pits ) at these relaxed regions will grow rapidly at the expense of the material around the pits ( or dots ) .\nthe fact that the large pits are deeper ( up to 100 nm and more ) than the wetting layer thickness implies that the arsenic atoms are also pumped out from the substrate and probably replaced by the phosphorus atoms . the similar cooperative nucleation of the dots pits pairs was detected at the growth of inas qds on gaas substrate , gaas / algaas qd pairs and at the growth of in 0.53 ga0.47 as layers on inp(001 ) substrate .\nthe effect of island density on pit nucleation in in0.27 ga0.73 as films grown on gaas(001 ) substrate is discussed in .\nlarge pits banded by the quantum wires in order to be confident , we calculated the gibbs free energy of inassbp quaternary alloy , as well as separately of inas - insb , inas - inp and insb - inp ternary alloys .\nwe found that at t = 550 c ( our growth temperature ) , the gibbs energy has the minimal value at x = 0.39 for inas1xsbx and at y = 0.52 for inas1ypy alloys .\notherwise , for the insb1zpz ternary alloy at the same temperature , the sufficiently wide immiscibility gap is exist at 0.05 < z < 0.97 . in this concentration range , the gibbs energy increases ( from the both sides ) and the mixing of these binary compounds becomes energetically not preferable .\nthis result marginally proves our assumption that at the nucleation of inassbp quaternary dots and pits , the surface diffusion of the antimony and phosphorus in opposite direction has to be energetically more preferable .\nin addition , note that with the increasing of the liquid phase initial concentration , the islands and pits shape transformation from the truncated pyramids to ellipsoidal and globe shape was detected .\nfigure 2a displays the sem and afm images of the inassbp unencapsulated dots pits cooperative structure in plain view for the surface area of s = 4 m . in this figure\nthe qds and pits are clearly visible and quite uniformly distributed over the substrate surface .\nfigures 1b , 1c and 2b2d show that cooperative nucleation of the dots pits structures is occurring . in\npits are banded by quantum wires and that the qds are banded by pits ( in the form of nano - camomile ) .\nb , c and d enlarged view of the mentioned by red , blue and green ovals related regions .\nwhite ovals qds , black ovals pits our statistical explorations show that the small qds average density ranges from 0.8 to 2 10 cm , with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm , respectively .\nthe average density of the small pits is equal to ( 610 ) 10 cm with dimensions of 540 nm in width and depth .\nsurface density of the large dots and pits is less by almost on two orders of magnitude .\nsmall qds and pit amount , and surface density versus their average diameter calculated from the surface of s = 4 m is detected and displayed in fig .\ndependence of the inassbp strain - induced qds and pits amount ( a , b ) and surface density ( c , d ) versus their average diameter ( s = 4 m ) .\n slezov approximations we used the fourier transform infrared spectrometry ( ftir nicolet / nexus ) to investigate the transmission spectra ( see fig .\n4 ) of an unencapsulated inassbp dots pits cooperative structure at room temperature . as a test sample\nthe result shows the displacement of the absorption edge toward the long wavelength region from = 3.44 m ( for test sample ) to = 3.85 m , as well as the enlargement of the absorption spectrum up to = 2.75 m short wavelength region .\nwe assume that this effect is the result of the absorption by the qds through the permitted energy sub - band .\npits cooperative structure grown on inas(100 ) substrate schematic diagram showing the type ii inassbp / inas qds is presented in fig .\n1 . whereis the planck constant , is the light holes effective mass , is the average diameter of qds andis the integer .\nthe similar approach was applied in . for our experimental system ( at light holes confinements ) , ( at ) , ( at ) , sub - band depth .\nnumerical value for the light holes effective mass for our inas1xysbxpy quaternary system was calculated by the linear approximation of the corresponding values for binary compounds at x = 0.04 and y = 0.08 .\nschematic view of the zone diagram showing the type ii inassbp / inas qds pits cooperative structure .\nnumerical values for b , c , d and e energies are approximate and based on ftir measurements and calculations finally , note that at the growth of diode heterostructures with the quantum dots and pits inside p n junction spatial charge region , the main challenge to overcome is providing the lateral overgrowth of the pits ( providing reverse qds ) and keeping the dots size during epitaxy of the cap epilayer .\nwe assume that by using step - cooling lpe , the growth of the cap epilayer from the strongly cooled liquid phase will address this problem .\nthus , we have presented an example of the inassbp quaternary qds , pits and dots pits cooperative structures growth on the inas(100 ) substrates by lpe . the interaction and surface morphology of the dots pits combinations were investigated .\nlifshits slezov - like distribution for the amount and surface density of small qds , and pits versus their average diameter was experimentally detected .\napplication of the inassbp and other similar quaternary materials opens up interesting physical and technological prospects for the dirigible growth of qds , pits and dots pits cooperative systems . by the corresponding and independent variations of the v - group elements concentrations ,\nthe results of our study can be also used for producing controlled arrays of strain - induced qds , which is very important for the fabrication of wide - band photodiodes , thermo - photovoltaic cells and other inas - based mid - infrared devices .\nthis work was carried out in the frame of armenian national governmental program for nano - electronics and istc grant a1232 .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .", "answer": "an example of inassbp quaternary quantum dots ( qds ) , pits and dots pits cooperative structures growth on inas(100 ) substrates by liquid phase epitaxy ( lpe ) is reported . \n the interaction and surface morphology of the dots pits combinations are investigated by the high - resolution scanning electron microscope . \n bimodal growth mechanism for the both qds and pits nucleation is observed . \n cooperative structures consist of the qds banded by pits , as well as the large pits banded by the quantum wires are detected . \n the composition of the islands and the pits edges is found to be quaternary , enriched by antimony and phosphorus , respectively . \n this repartition is caused by dissociation of the wetting layer , followed by migration ( surface diffusion ) of the sb and p atoms in opposite directions . the small qds average density ranges from 0.8 to 2 109 cm2 , with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm , respectively . \n the average density of the small pits is equal to ( 610 ) 109 cm2 with dimensions of 540 nm in width and depth . lifshits slezov - like distribution for the amount and surface density of both \n small qds and pits versus their average diameter is experimentally detected . \n a displacement of the absorption edge toward the long wavelength region and enlargement toward the short wavelength region is detected by the fourier transform infrared spectrometry .", "id": 733} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe term was used by hallopeau in 1889 and is derived from the greek ; thrix - hair , tillein - pull out and mania - madness .\nscalp is the most common site for pulling hair although other hair bearing areas may be involved . in less severe forms\ndiagnosis is mainly by history and clinical examination , nevertheless , sometimes it is very difficult to differentiate it from other causes of noncicatricial alopecia .\ntrichoscopy , dermoscopy hair and scalp , is a noninvasive technique for differential diagnosis of various hair and scalp diseases . here\nauthors evaluated trichoscopic patterns in ttm and authors believe that these patterns are specific to ttm , which can aide in early diagnosis of this chronic condition .\nthis study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 .\nten patients with clinical features of ttm were subjected for a complete history and dermatological examination .\ndemographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .\ndermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study .\nsony camera ( digital , 14 mega pixels ) was attached to save the images .\ninitially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy .\nalthough polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light .\nthis study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 .\nten patients with clinical features of ttm were subjected for a complete history and dermatological examination .\ndemographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .\ndermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study . however , only polarized light version was used in our study .\nsony camera ( digital , 14 mega pixels ) was attached to save the images .\ninitially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy .\nalthough polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light .\nmean age of the patients was 34 years ( minimum age 13 years and maximum age 55 years ) .\nmean duration of disease was 19 months ( minimum 2 months and maximum 36 months ) .\nmost common symptom was patchy loss of hair over the scalp ( 100% ) especially in the frontal area [ figure 1 ] and one patient ( 10% ) had tonsure pattern of hair loss .\nfour patients agreed to knowingly pulling of hair , and one patient ( 10% ) gave a history of eating them ( trichophagia ) .\nthe most common trichoscopic pattern observed in all patients was decreased hair density and hairs broken at different lengths ( 100% ) [ figure 2 ] .\nexcoriations are also seen on the forehead trichoscopy showing decreased hair density , trichoptilosis ( yellow arrows ) , tulip hairs ( red arrows ) and perifollicular whitish areas ( red stars ) short hair with trichoptilosis ( split ends ) [ figures 25 ] , irregular coiled hairs [ figure 3 ] and upright re - growing hairs were demonstrated in 8 patients ( 80% ) each .\nthe novel diagnostic signs like black dots and flame hair [ figure 4 ] , v - sign [ figure 3 ] , follicular hemorrhages [ figure 5 ] were observed in 3 patients ( 30% ) each .\ntulip hair and hair powder [ figure 6 ] patterns were observed in 1 ( 10% ) patient each .\nall patients ( 100% ) had the noninflammatory alopecia with follicles having distorted and collapsed inner root sheath [ figure 7 ] in histopathology .\ntrichoscopy showing coiled hairs ( red arrows ) and v - hairs or v - sign ( yellow arrows ) trichoscopy showing flame hairs ( red arrows ) and black dots ( yellow arrows ) trichoscopy showing decreased hair density , follicular hemorrhage ( black arrow ) and trichoptilosis ( red arrows ) trichoscopy showing tulip hairs ( red arrows ) and hair powder ( yellow arrows ) histopathology showing diffuse , noninflammatory alopecia , missing hair shafts ( black stars ) and inward collapse of outer root sheath ( black arrows ) .\nfew unaffected follicles are also seen ( yellow arrows ) ( h and e , 4 ) histopathology showing an irregular , deformed and pigmented shaft characteristic of trichomalacia ( h and e , 40 )\ntrichotillomania is a chronic impulse control disorder characterized by repetitive hair pulling resulting in alopecia . in young children , it is usually a habit that resolves spontaneously or with minimal treatment . in older age groups , adolescents and adults ,\nseen predominantly in females and evidence of some form of psychological or behavioral stress is often apparent .\nthe favorite site is the easily reached fronto - parietal region of the scalp followed by eyelashes , eyebrows , pubic hair , body hair and facial hair .\nthis results in patchy loss of hair , often in a bizarre or angular pattern , in which the hairs are twisted and broken at various distances from the clinically normal scalp .\na hairball , trichobezoar , is a rare accompaniment of ttm in those who also eat the plucked hair ( trichophagia ) . in our study ,\nmost of the patients belonged to adolescent , and middle age group and most of them were females .\nall of them presented with patchy hair loss over the scalp , none of the patients gave a history of hair loss in other areas .\nonly one patient had a history of eating of pulled hairs , but there were no signs and symptoms of trichobezoar in her .\nthe diagnosis of ttm is often difficult as other hair loss diseases appear similar in clinical manifestations .\nthis difficulty is encountered especially with alopecia areata ( aa ) . as ttm often coexists with aa\ntrichoscopy is a novel diagnostic technique , both simple and noninvasive , can be used as a handy bed side tool for diagnosing common hair and scalp disorder .\nseveral common trichoscopy features of ttm were identified . decreased hair density , hairs broken at different lengths , short hairs with trichoptilosis ( \" split ends \" ) are described in the literature as diagnostic of ttm .\nauthors observed these findings in all the patients , and this is due to irregular and repetitive pulling of hairs leading to damage to the cuticle . irregular coiled hairs and upright re - growing hairs are also reported to be seen in ttm . in this study , these findings were demonstrated in 80% of patients . coiled hair results from hair shaft fracture and coiling of the remaining proximal part which is fixed to the scalp .\nblack dots are believed to be remnants of hair shafts arising from tapering hairs , broken hairs , and bent hairs . in a study conducted by shim et al .\nrakowska et al . observed that black dots tend to be uniform in size and shape in aa , whereas in ttm and tinea capitis they are variable in diameter and round , oval , irregular in shape .\nit presents as a red dot corresponding to follicular ostia capped or stuffed with the blood clot and suggests a history of traumatic forced plucking .\nrecently , flame hairs , v - sign , tulip hairs , and hair powder are described , and authors claim these signs are specific only for ttm .\nflame hairs are semi - transparent , wavy and cone - shaped hair residues , which develop as a result of severe mechanical hair pulling and shredding .\nv - sign is created when two or more hairs emerge from one follicular ostium , which are pulled simultaneously and break at the same length above scalp surface .\nwhen hair shafts are almost totally damaged by mechanical manipulation , only a sprinkled hair residue is visible .\nthis finding is referred to as hair powder . in the present study , these trichoscopic patterns were demonstrated in variable frequency . in aa , the common trichoscopic findings are yellow dots , uniform black dots , broken hair , trichoptilosis , upright re - growing hair , and vellus hair .\nas some of the trichoscopic features are overlapping in ttm and aa , histopathology plays a corroborative role in definitive diagnosis .\nthe histopathological features of ttm include empty follicles , incomplete disrupted follicular anatomy , trichomalacia , and pigment casts without significant inflammation .\ncollapsed inner root sheath and missing hair shaft indicate the extraction of the hair follicle due to forcible hair pulling . partially extracted and distorted root sheath material with fragments of pigment can be identified as \nthe germinative follicular epithelium may produce abnormally formed , diminished and distorted hair shaft with irregular pigmentation as a result of trauma .\na new trichoscopic pattern was observed by the authors in one patient , in the form of perifollicular whitish areas [ figure 2 ] .\nauthors believe these whitish areas represent hyperkeratosis that is due to perifollicular damage as a result of repeated hair pulling\ntrichotillomania is often chronic and difficult to treat . patients may attempt to disguise the condition due to its social implications . hence\ntrichoscopy , being a noninvasive and in vivo diagnostic technique , can be utilized in this condition as it plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns .\nfurther studies on trichoscopic patterns correlating with duration of disease and histopathology of ttm are suggested .", "answer": "introduction : trichotillomania ( ttm ) is characterized by patchy alopecia of hair bearing areas . this is because of compulsive urge to pull the hair . \n scalp is the most common site for pulling hair . \n usually , patients may have only small areas of baldness , in severe forms , tonsure pattern of baldness is observed . \n diagnosis is by history and clinical examination . \n however , it is difficult to differentiate from other causes of noncicatricial alopecia . here , authors observed trichoscopic patterns and evaluated their importance in the diagnosis of ttm.materials and methods : this study was conducted in s. nijalingappa medical college , bagalkot , from january 2014 to july 2014 . \n ten patients with clinically suspected ttm were included in the study . \n informed consent was taken and ethical clearance was obtained . \n dermlite3 dermoscope was used with sony camera attachment to save the images . \n histopathological examination was conducted in all the patients to confirm the diagnosis.results:ten patients were included in the study . \n mean age of the patients was 34 years . \n most common symptom was patchy loss of hair in the frontal area ( 100% ) . \n common trichoscopic feature was decreased hair density and broken hairs . \n trichoptilosis ( split ends ) and irregular coiled hairs were seen in 80% patients . \n novel diagnostic signs like black dots , flame hair , v - sign , follicular hemorrhages , were seen in 30% each . \n tulip hair and hair powder were observed in 10% of patients . \n all patients had the noninflammatory alopecia with distorted and collapsed inner root sheath in histopathology.conclusion:trichotillomania is often chronic and difficult to treat . hence \n , early diagnosis and treatment is necessary . \n authors believe that the trichoscopy plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns .", "id": 734} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe syndrome with ectrodactyly , ectodermal dysplasia , cleft lip and cleft palate ( eec ) is a complex disease with a variety of abnormalities of the ectodermal and mesodermal germinal layer . the first author who described this disease was eckoldt in 1804 .\nsplit hands or feet are characterized by agenesis of the third ray and possible fusion of the remaining fingers or toes .\nthe ectodermal component of this syndrome includes hair with hypotrichosis , hypopigmentation , the teeth with hypodontia , enamel hypoplasia and microdontia and ultimately the nails , which present themselves dystrophic in most cases .\na number of associated anomalies are also frequently found . in the 230 published cases , 84% of patients presented with split hands or feet .\ndysplasia of the ectoderm arises in 77% of patients and clefts appear in 68% of cases .\nimportant hints may indicate an eec syndrome already in the clinical examination of the patient and in the investigation of family history .\ntwo case reports of our department shall demonstrate the management of eec syndrome affected patients with all - in - one closure of the lip cleft and palate cleft and the treatment regimen in manifest ectodermal dysplasia .\na newborn baby with a unilateral complete cleft lip and palate ( left side- cleft palate width 23 mm ) first child of non - consanguineous marriage was referred to our department . additionally , the child presented a deletion of the central finger on the right hand and fusion of the second and third finger on the left hand as well as fusion of the second and third toe on both feet . paper - thin , dry and reddened skin and sparse scalp hair were also visible ( figure 1 ) .\nthe father suffered from the eec syndrome , too- , showing similar hand malformation and a bilateral cleft lip and palate , which was treated in multiple surgeries . in our patient ,\nfeeding of the child was possible with a palate obturator . for ( naso)alveolar molding lip taping with an elastic plaster ( dynacleft , barrie on , canada )\nthe cleft lip width was still 12 mm . for improved soft - tissue conditioning , lip adhesion\ntwo months later , the one - step procedure of the cleft lip and palate closure was performed .\nthe operative procedure involves firstly in intravelar veloplasty with microscopic view , secondly in restore the nasal floor with two choanes and pedicled flaps without push back and at the end doing only a gingivoperiosteoplasty but without touching the germ area . at the end , a palatal plate was fitted for 7 days . in our protocol , we do a secondary osteoplasty with 9/10 years of age .\nthe operation time was 60 min for the palate . during the closure of the palate to prevent pressure damage on the tongue the mouth gag was often released .\nnevertheless , after surgery , the child had to be re - intubated at the intensive care unit due to an exfoliative stomatitis and dramatic swelling of the back of the tongue with impairment of the upper respiratory tract ( figure 3 ) .\nsupportive treatment with an anti - edematous and anti - inflammatory medication ( cortisone intravenously ) was initiated\nthe further post - operative course of treatment was without complications ( figure 4 ) .\nwe suppose that there is a connection with the eec which makes the tissue more sensitive but this is a hypothesis that is not proven .\nthe clinical examinations showed a complete cleft lip and palate ( left side ) and deletion of the central finger on the right hand , fusion of second and third finger of the left hand and fusion of the second and third toe on both feet .\nswelling of the back of the tongue and exfoliation after the all in one closure and before re - intubation .\nfollow - up 6 months after surgery with harmonious upper lip and no abnormalities in the epidermis . until now , no treatment concerning hands and feet was performed .\nthis case presents the sister of the above described boy , born 3 years and eight months later : born at 38 week of gestation with a birth weight of 2985 g she showed a bilateral cleft lip , syndactyly on all extremities and a conspicuous dryness of the skin ( figure 5 ) .\nclinical findings and the family history lead again to the eec syndrome . similar to the brother an obturator plate with nasoalveolar molding was adapted . at the age of 8 weeks a lip adhesion was performed . with 4.5 months\nthe clinical examination of the patient 3 h after birth shows the typical characteristics for the eec - syndrome .\nno complications have occurred in wound healing due to the eec - syndrome until now , no treatment concerning hands and feet was performed .\n. characterized by ectrodactyly , ectodermal dysplasia , cleft lip and/or cleft palate . since then , numerous reports in the literature have expanded the clinical appearance .\nthe transmission is usually autosomal - dominant trait with variable expressivity and reduced penetrance [ 4 - 6 ] .\nsome authors believe that the classic case of the eec syndrome is caused by mutation of the p63 gene .\nthe variability in the phenotypic expression is explained by the interaction of ectodermal with the mesodermal germ layer .\nthe eec syndrome must be differentiated from other syndromes , which also show an ectodermal dysplasia and orofacial clefts as the rapp - hodgkin syndrome , the aec syndrome ( syndrome with ankyloblepharon filiform adnatum , ectodermal dysplasia and cheilognathopalatoschisis , [ 10 - 12 ] ) .\nothers have their own characteristics , for example the rapp - hodgkin syndrome presenting a short stature and special lineaments .\nthe eec syndrome has to be distinguished from other diseases with acral anomalies and oral cleft , including the acrorenal syndrome and from the fetal alcohol syndrome .\nminor anomalies of the eec syndrome are renal malformations , deafness , mental retardation and choanal atresia .\nother recently reported associated anomalies are the insufficiency of the pituitary gland , anorectale malformations and hypoplasia of the thymus .\nuntil now , three types of eec syndrome and their respective gene loci were molecularly identified .\nbalanced chromosome changes or interstitials deletions were found : type 1 is linked to gene locus 7q11.21q21.3 , type 2 and type 3 with chromosome 19 locus with 3q21 ( p63 ) [ 21 - 23 ] .\nrecently , heterozygous mutations in the p63 gene have been shown to 3q27 by amino acid substitutions in the dna - binding domain , which are considered as the main cause for the formation of the gap in hands and feet [ 25 - 27 ] .\nthe ultrasound in prenatal diagnosis plays an important role in the early detection of ectrodactyly and cleft lip and palate [ 28 - 30 ] . for a more accurate prenatal diagnosis of this syndrome ,\na molecular study was introduced . with the use of a dna extraction from fetal chorionic villi\n, a prenatal dna analysis can be carried out in a pregnancy at risk for the eec syndrome .\n, eec children will be treated like other non - syndromic cleft patients . in the first 24 h after birth , an obturator plate and\nif necessary and due to dry skin possible , upper lip taping is adapted for alveolar molding .\nthe gastric tube see in figure 4 was removed after the obturator plate was inserted . if the cleft lip remains more than 15 mm a lip adhesion is an option .\nnormally , this will be performed at the age of 8 weeks , in the first case it was delayed due to surrounding circumstances . approximately 8 weeks later , a closure of all layers in a single operational step will be performed .\none - stage procedures with 34 months can lead to disturbance in growth of the maxilla , but the extend was similar to the mean values of multistage procedures assessed in the eurocleft study .\nchildren and their parents have no further psycho - social stress due to multiple surgical interventions at an early age .\nthe main therapeutic approach depends on the expression of the ectodermal dysplasia and should be evaluated individually for each patient .\nit is mandatory that the patient has a close follow - up with , if necessary , functional physiotherapy , speech therapy and early functional orthodontic care .\nwhenever cases of eec syndrome occur , it is important , according to their phenotypic characteristics , to follow an interdisciplinary approach to reduce complications , to minimize undesirable sequelae and provide the best possible medical care .\nethics and consent : a written consent from the parents for the publication of photos is available .", "answer": "we report on siblings who suffer from eec syndrome and show our experiences of the \" basel concept \" of cleft lip / palate repair based on the early , one - stage closure of all components . \n it is performed in the age of 34 months to provide early normal conditions for anatomy and muscle function .", "id": 735} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhypophosphatemic rickets ( hr ) is a metabolic bone disorders manifested by musculoskeletal disorders specially in the lower extremities , growth retardation and dental problems[1 , 2 ] .\nthis disorder affects all ages and both sexes and is characterized by a low concentration of serum phosphate , elevated alkaline phosphatase , normal or decreased serum calcium and inappropriate levels of 1,25-dihydroxy - vitamin d [ 1,25 ( oh)2 vit d][1 , 3 ] .\nmusculoskeletal disorders are due to mineralization impairment of the bone matrix and teeth with different etiologies .\nx - linked hypophosphatemic rickets ( xlhr ) is the most common form of the genetic disorders causing rickets due to hypophosphatemia .\nthis disorder results from mutation in the phex gene and the product of this gene has a role in phosphatonin inactivation .\nhr is more common in females with positive family history observed in 35.3% patients , nevertheless , it seems this disorder is more frequently and more severe among males in xlh form .\ncommon features are a short stature , backache , body deformities , joint pain , and fractures .\ndental abnormalities include dental taurodontism with increasing mean crown - body to root ratio , ectopic permanent canines , dental abcesses[2 , 5 ] and enamel hypoplasia .\ntreatment of rickets with vitamin d ( vit d ) and phosphate supplements has been shown to prevent and cure the dental anomalies in some but not all patients . from 1970 ,\ndental problems were reported in 23 - 67% xlhr patients[3 , 6 , 7 ] , but these problems have not been described well in previous studies .\nthis study was a cross sectional investigation that was conducted in a referral pediatrics endocrinology clinic in iran during 3 years ( 2008 - 2010 ) .\nthe diagnosis of hypophosphatemic rickets was made on the basis of clinical and radiological findings of rickets in a patient with low level of serum phosphate , normal or low level of serum calcium ( < 8.2 mg / dl ) and normal levels of 25(oh)2-vit d ( < 15 pg / ml ) , and normal or mildly elevated pth with high level of serum alkaline phosphatase ( > 55 pg / ml ) .\npatients who did not have a clear diagnosis or refused to participate in the study were excluded . after taking a dental history , all subjects had a dental examination ( including dental caries , enamel hypoplasia , taurodontism , dental abscesses and gingivitis ) ; opg was performed if necessary .\nclinical examination was performed to look for dental deformities by a trained dentist for all patients .\ninformation about dental problem including : dental abscess , enamel hypoplasia , dental caries , gingivitis , taurodontism , and delay in the primary or permanent dentition was obtained . for permanent teeth , decay , missing , or filled teeth ( dmft ) index and for primary teeth , decay or filled teeth ( dft )\ndelay in eruption of teeth was based on times of eruption of the primary and permanent teeth from logan and kronfeld .\ntaurodontism was suggested if there was any change in tooth shape and was confirmed by orthopantomography ( opg ) .\nin this study we enrolled 19 patients with hypophosphatemic rickets . mean age of these patients was 104.23 years ( range 3 - 17 ) .\neleven ( 57.9% ) patients were female and 8 patients ( 42.1% ) male ( female to male ratio : 2/1.3 ) . fifteen ( 79% ) patients had regular follow - up after diagnosis of background disease and 17 ( 89.5% ) patients had at least one dental problem .\nthe most common dental problems were dental caries and delay in eruption of the dentition in 9 ( 47.7% ) patients .\nenamel hypoplasia was found in 8 ( 42.1% ) patients and 3 ( 15.8% ) patients had taurodontism and all last group were male . both dental abscesses and gingivitis were found in 2 ( 10.5% ) patients .\nsix ( 54.5% ) female and 3 ( 37.5% ) male patients had dental caries .\nthe prevalence of dental caries was significantly more frequent in case group ( p=0.04 ) that was 10.5% in healthy control matched group .\nthis study showed that hr has a variable age of presentation and it was more common in females[2 , 3 ] .\ndental caries was the most common finding in this study ( 47.7% ) that was similar to chaussain - miller 's study .\ndental caries is one of the most common factors for pulp infection , so oral hygiene has an important role for caries prevention .\ndental abscesses were found in 10.5% of the patients compared to 25 - 65% in other studies[4 , 6 , 12 ] . in patients with hr\nthe dentition is highly susceptible to dental caries and bacteria can invade easily from the oral cavity to the dental pulp by means of structural defects in the enamel .\ndifference of prevalence of dental abscess may be due to early diagnostic and treatment of these patients , although shroff et al believe that prophylactic pulpotomy therapy may have been no benefit in preserving the primary dentition in xlhr patients . in our study ,\nenamel hyperplasia has been reported in 16.6% patients with permanent teeth by bender and naidorf , however they said the incidence of this disorder is 36.8% ( 14/38 ) in cases reported in the literature , this is similar to our study .\nalthough this phenomena is expectable in hr patients , no significant differences was reported in dental age compared with the respective chronological age in a study .\ngenetic mechanisms have a main role causing defective dentition and dentine mineralization . in this study taurodontism had a significantly increased tendency in male xlhr subjects .\nsimilar findings were reported by seow et al . in a controlled , longitudinal study , they showed taurodontism had a significantly higher tendency in male xlhr patients . patients respond well to a combination of oral phosphate and 1,25(oh)2-vitd ( calcitriol)[4 , 6 ] .\nthe beneficial dental effect of phosphate supplements after birth and the possible influence of maternal phosphate homeostasis suggest that most abnormal dental features are linked to hypophosphatemia and deficient renal production of 1,25(oh)2-d .\nsome effects of 1,25(oh)2-d on dentin may be indirect , through an increased intestinal absorption of calcium and phosphorus .\n1,25(oh)2-d may also exert some direct effect on dental cells , as odontoblasts and ameloblasts express the vitamin d receptor and respond in vitro to this vitamin .\nit seems , the best results were achieved when medication started during early childhood[4 , 18 ] .\ndental care of these patients should consist of periodic examination , topical fluoride application , pit and fissure sealants and maintenance of good oral hygiene .\ndental caries as common as delay in dentition were the most prevalent problems in xlhr patients that could be reduced by proper dental care and good oral hygiene .\nso the dentist as well as pediatrician should be made aware of the features of disorder and early intervention .", "answer": "objectivehypophosphatemic rickets is an uncommon metabolic bone disorder which affects all ages and both sexes . \n it is characterized by low concentration of serum phosphate levels , impairment of mineralization of bone matrix and teeth with variable etiology . \n dental problems in this disorder have not been described well in previous studies.methodsall hypophosphatemic rickets patients who came to a referral clinic during 2008 - 2010 enrolled in this study . \n all patients had low phosphorous and high alp , normal pth and 25-hydroxy - vitamin d and normal or low level of serum calcium . \n after diagnosis all patients were examined by a dentist for enamel hypoplasia , taurodontism , dental abscess , gingivitis , dental caries , and dentition delay.findingsnineteen patients were enrolled in this study . \n the average age of the patients was 10 ( 4.23 ) years ( range 3 - 17 ) . \n seventy - nine percent of patients had regular follow - up after diagnosis of background disease . \n dental caries and delay in the dentition were most prevalent ( each one 47.7% ) followed by enamel hypoplasia in 42.1% of the patients . \n other problems were taurodontism in 15.8% patients , dental abscess and gingivitis in 10.9%.conclusionhypophosphatemic rickets is a disease with different clinical features ; one of them is dental problem , dental caries is the most common problem .", "id": 736} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrecent studies revealed that plants contain populations of small rnas ( 2025 nt ) that belong to two major classes micrornas ( mirnas ) and endogenous short - interfering rnas ( sirnas ) .\nmirna gene transcripts adopt imperfect foldback structures and are processed by dicer - like 1 ( dcl1 ) , resulting in 2022 nt mirnas .\nmature mirnas function as post - transcriptional regulators that guide either site - specific cleavage or non - degradative repression of target mrnas ( 1 ) . in many cases ,\nsirnas arise from endogenous transcripts that form dsrna structures , or that are substrates for rnai pathways .\nprocessing of sirnas often requires other dcl proteins , such as dcl3 ( 11 ) .\nin addition , biogenesis of several classes of endogenous sirnas requires rna - dependent rna polymerases , such as rdr2 ( 11 ) .\nsirna - generating loci often yield multiple , overlapping clusters of small rnas , in contrast to mirna loci that generally yield a single mirna .\nendogenous sirnas arise from repetitive sequences , transposons and retroelements , genomic regions containing inverted duplications , as well as other genic and intergenic regions .\na subset of sirnas also act to guide or assist formation of heterochromatin ( 1214 ) .\na subclass of sirnas has been shown to guide cleavage of specific target mrnas in trans , similar to mirnas .\nbiogenesis of trans - acting sirnas ( ta - sirnas ) requires dcl1 and rdr6 ( 15,16 ) .\nin contrast to mirna genes , ta - sirna precursor transcripts do not form a foldback structure , but rather both sense and antisense small rnas are processed from perfectly complementary rna duplexes .\nseveral small rna libraries have been constructed from arabidopsis thaliana plants with the primary goal to identify mirnas and endogenous sirnas ( 1722 ) .\nthe aim of the arabidopsis small rna project ( asrp ) is to analyze small rnas from different tissues and genotypes of arabidopsis , provide a public database of cloned small rna sequences and develop web - based tools to assist in analysis of small rna populations .\nthese resources are intended to aid the identification of mirnas and mirna genes , and to enable functional analysis of sirna - producing regions of the genome .\nthe collection represents small rna sequences from both in - house cloning projects and sequences deposited in the mirna registry ( 23 ) . for sequences derived in - house ,\nmultiple small rna libraries were constructed from arabidopsis ( columbia-0 ecotype ) at various developmental stages , including embryos , 3-day post germination seedlings , aerial tissues ( including rosette leaves and apical meristems ) and inflorescences ( stages 112 ) . to genetically enrich for mirna populations ,\nlibraries were constructed from rdr2 - 1 and dcl3 - 1 mutants that have defects in the chromatin sirna pathway .\n. the asrp graphical user interface ( gui ) is composed of web pages delivered by an apache http server ( http://httpd.apache.org ) . in addition , the server incorporates mod_perl ( http://perl.apache.org ) and mason ( http://www.masonhq.org ) to dynamically produce web pages based upon user input .\nthe vast majority of the gui is generated by custom perl code that increasingly incorporates object - oriented coding practices to improve extensibility and re - usability of the individual software components .\nbioperl ( 24 ) is used for specific tasks , such as parsing the genbank files containing the arabidopsis chromosomes .\nthe gui interacts with a custom database backend utilizing structured query language ( sql ) and the open source mysql ( http://www.mysql.com ) database engine .\ntable structures and specific query statements conform to standard sql language syntax and are portable to other sql database engines .\ncurrently , the asrp database resides on a custom - configured server managed by the redhat linux as operating system .\nthe asrp database web interface enables users to view and analyze the small rnas in text and graphical formats .\ndata for each small rna is stored in mysql database tables that are easily sorted and searched . through the web interface\n, users may sort and view the small rna data in the following ways : \n all small rnas .\nthis page displays basic information about all unique small rnas in the database , including , if applicable , the mirna or ta - sirna name , number of loci in the arabidopsis genome , number of near predicted loci in the rice genome , number of potential mrna targets and number of times isolated .\nmore information about a specific small rna is available by following the database number ( dbe # ) link.small rna clusters .\nthis page displays clusters containing a minimum of four small rna loci , with each within 500 nt of the next small rna loci . from this page\n, the user can view the sequences and positions of the small rnas in each cluster in text format or the cluster can be viewed graphically in relation to the arabidopsis genome using an open access genome viewer ( 25).mirnas . all small rnas characterized as mirnas are displayed in a similar format as section ( i ) ( figure 1a ) .\nthe display page for each individual mirna is split into four sections ; general information , arabidopsis mirna genes , predicted and validated target genes , and oryza sativa mirna genes ( figure 1b ) .\nthe predicted foldback structure for the pre - mirna , the flanking sequence around the mirna gene and the graphical genome view are available through links on the arabidopsis mirna genes section ( figure 1c ) .\ninformation about the predicted target genes , the target - mirna binding site , and the computational or experimental validity of the target - mirna binding site is displayed in the third section ( figure 1b ) .\nthe fourth section displays information about the small rna in o.sativa , including the predicted secondary structure of validated precursor mirnas.ta-sirnas .\ngeneral information , ta - sirna - generating locus information , and predicted target genes are displayed .\nthe user can view the information about the ta - sirnas in a manner similar to the mirna section of the database.annotated small rnas .\nautomated annotation programs such as repeatmasker ( http://ftp.genome.washington.edu/rm/repeatmasker.html ) are used to identify small rnas that originate from genomic regions of highly repetitive sequences , as well as transposons and retroelements .\nthe user can display and sort small rnas by the specific class of annotated repeat element such as mudr or sine .\nthis page displays basic information about all unique small rnas in the database , including , if applicable , the mirna or ta - sirna name , number of loci in the arabidopsis genome , number of near predicted loci in the rice genome , number of potential mrna targets and number of times isolated .\nmore information about a specific small rna is available by following the database number ( dbe # ) link\nthis page displays clusters containing a minimum of four small rna loci , with each within 500 nt of the next small rna loci . from this page\n, the user can view the sequences and positions of the small rnas in each cluster in text format or the cluster can be viewed graphically in relation to the arabidopsis genome using an open access genome viewer ( 25 ) .\nall small rnas characterized as mirnas are displayed in a similar format as section ( i ) ( figure 1a ) .\nthe display page for each individual mirna is split into four sections ; general information , arabidopsis mirna genes , predicted and validated target genes , and oryza sativa mirna genes ( figure 1b ) .\nthe predicted foldback structure for the pre - mirna , the flanking sequence around the mirna gene and the graphical genome view are available through links on the arabidopsis mirna genes section ( figure 1c ) .\ninformation about the predicted target genes , the target - mirna binding site , and the computational or experimental validity of the target - mirna binding site is displayed in the third section ( figure 1b ) .\nthe fourth section displays information about the small rna in o.sativa , including the predicted secondary structure of validated precursor mirnas .\ngeneral information , ta - sirna - generating locus information , and predicted target genes are displayed .\nthe user can view the information about the ta - sirnas in a manner similar to the mirna section of the database . annotated small rnas .\nautomated annotation programs such as repeatmasker ( http://ftp.genome.washington.edu/rm/repeatmasker.html ) are used to identify small rnas that originate from genomic regions of highly repetitive sequences , as well as transposons and retroelements .\nthe user can display and sort small rnas by the specific class of annotated repeat element such as mudr or sine .\nin addition to the sorting features , the web interface provides users with a variety of searching capabilities .\nquick searches enable users to locate specific mirnas based on either the mirna names or the asrp database identifiers ( dbe # ) .\nto search for small rnas predicted to target specific arabidopsis genes , or that originate from generic sequences , the locus identifiers ( e.g. at3g60630 ) or user - defined fasta formatted sequences are used , respectively .\nfinally , users can determine if a small rna sequence is represented in the asrp database by searching the sequence against the entire population of small rnas .\nall small rnas in the asrp database are available through the publicly available website ( http://asrp.cgrb.oregonstate.edu ) or can be downloaded in fasta format from the website download page ( http://asrp.cgrb.oregonstate.edu/downloads/ ) .\nthe asrp database was created to serve as a repository and tool to facilitate the analysis of mirnas and endogenous sirnas and their targets . to increase accessibility of the database , we are working to more completely integrate the asrp database with existing arabidopsis resources , such as tair .\nin addition , integration of mirnas , ta - sirnas and endogenous sirnas from the database with other research projects , such as genomic tilling microarrays and chromatin immunoprecipitation arrays ( 14,26 ) , will enhance the information acquired from these experiments and further expand our understanding of small rna function .\nthere are still many unanswered questions concerning mirnas , ta - sirnas and endogenous sirnas .\nthe regulatory roles of mirna - target gene interaction , the regulation of mirna gene expression , and the function of sirnas in the regulation of chromatin structure and gene silencing are just a few questions currently being studied .\nfuture plans include the integration of data from genome - scale microarray projects into the asrp database ( 27 ) .\nthe scope of the database may widen with the addition of other plant genomes , libraries or computational analysis .\nthe inclusion of additional plant genomes will enable a more in - depth study of mirna evolution and conservation and activities of endogenous sirnas .\nwe thank christopher m. sullivan for developing the infrastructure for the computing cluster and compiling the software technologies used for the database and heather fitzgerald for critical reading of the manuscript .\nthe arabidopsis small rna project database is supported by a 2010 project grant from the national science foundation ( mcb-0209836 ) .", "answer": "eukaryotes produce functionally diverse classes of small rnas ( 2025 nt ) . \n these include micrornas ( mirnas ) , which act as regulatory factors during growth and development , and short - interfering rnas ( sirnas ) , which function in several epigenetic and post - transcriptional silencing systems . the arabidopsis small rna project ( asrp ) seeks to characterize and functionally analyze the major classes of endogenous small rnas in plants . \n the asrp database provides a repository for sequences of small rnas cloned from various arabidopsis genotypes and tissues . \n version 3.0 of the database contains 1920 unique sequences , with tools to assist in mirna and sirna identification and analysis . \n the comprehensive database is publicly available through a web interface at http://asrp.cgrb.oregonstate.edu .", "id": 737} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n the prevalence of child obesity is increasing rapidly worldwide . based on the data of the world health organization ( who ) , over 30% of the people in the middle east are overweight .\na review of some studies from iran reveals that the prevalence of obesity among iranian children has been doubled between 1993 and 1999 , which could be attributed to the changes in lifestyle.1 \n , \n 3 \n , \n 4 obesity in adults is not easy to treat and is often correlated with obesity during childhood . \n \n in the last decade ,\nconsumption of soft drinks and fast foods together with less activity and exercise contributed to the increasing number of overweight people worldwide . along with increasing caries risk ,\nincreased consumption of sugar - sweetened beverages and snack foods also has been linked to obesity .\nhealth risks associated with childhood overweight and obesity are strong indicators for predisposition to adult morbidity and mortality and include type 2 diabetes , cardiovascular disease , fatty liver disease , early maturation , endometrial , colon , breast and other cancers , psychological stress , as well as orthopedic problems , general poor health , and hepatic problems.7 \n - \n 10 an iranian study detected a high prevalence of cardiovascular risk factors in overweight and obese children aged 7 - 12 years . \n \n\nobesity is also related to several aspects of oral health , such as caries , periodontitis and xerostomia .\nfruit drinks and other sweetened beverages represent high sugar sources , which may contribute to cariogenic potential .\noral health is strongly influenced by the daily intake of food and can also play a significant role in nutritional intake and general status of health , particularly in the elderly . who recommends limiting added sugars to 10% of total calories on the grounds that added sugars contributed to overall caloric density of the diet .\na study in scotland showed that among 165 children aged 3 - 11 years , whom with the worst decay were significantly thinner also severe dental decay was associated with underweight .\none brazilian study concluded that there was no statistically significant association between dental caries and obesity in adolescents aged 12 to 15 years . \n \n among children and teenagers aged 2 - 20 years , body fat amount changes as the body grows and is different for boys and girls .\nunlike body mass index ( bmi ) assessments for adults , assessments for children and teenagers take these growth and gender specific differences into account .\nthese child - specific bmi values are referred to as bmi - for - age . \ncategories describing amount of body fat for children and teenagers is also different from the categories describing amount of body fat in adults . among adults ,\nbmi categories include underweight , normal , overweight , and obese .\n among children and teenagers , bmi - for - age categories include underweight , \nsince the frequent consumption of high caloric and cariogenic substances are two of the many factors associated with caries and obesity , and to the best of our knowledge there are no studies that have investigated the association between bmi - for - age and dental caries in iran to date , the purpose of this study was to determine whether bmi - for - age , might be associated with dental caries in children in isfahan , iran . \n\n\n this cross - sectional study was conducted from june to august 2007 in isfahan , iran . using a random cluster sampling , a total of 1003 pupils aged 6 - 11 years from six private and state elementary schools with different social backgrounds\nthe children thoroughly chewed one disclosing tablet ( svenska dentorama ab , stockholm , sweden ) and rinsed their mouth with water , according to the manufacturer s instructions .\nthe children who had 70% or fewer teeth surfaces with plaque were invited for further evaluations .\nthe sample size was estimated allowing for caries prevalence of 60% , and significance level of 0.05 .\nall of the children participated in the clinical examination were iranians and permanent residents of the city .\nbody weight was recorded to the nearest 100-gram using a standard beam balance scale with the subject barefoot and wearing light dresses .\nthe balance was calibrated at the beginning of each working day and at frequent intervals throughout the day .\nbody height was recorded to the nearest 0.5 cm according to the following protocol : no shoes , heels together and head touching the ruler with line of sight aligned horizontally . to avoid subjective errors ,\nbmi - for - age percentiles , representing eating habits in children and teenagers , were used .\nbmi - for - age [ ( weight in kilograms ) / ( height in meters) ] percentiles are dependent on gender and age - specific weight for height curves for those aged 2 - 20 years . according to these curves ,\n underweight is defined as bmi - for - age < 5th percentile , \nnormal is defined as 5th percentile < bmi - for age < 85th percentile , at risk of overweight is defined as 85th percentile < bmi - for - age < 95th percentile , and \noverweight is defined as bmi - for - age > 95th percentile . since the number of samples in underweight group was insufficient ( three samples ) , this group was excluded from the study .\nthe remaining 633 children ( 317 boys and 316 girls ) enrolled in the study . \n \n\nall selected children were clinically examined for dental caries by a specialist utilizing the who criteria for diagnosis of dental caries .\nthe examination was carried out using a cycle and cow horn two - headed dental explorer ( aesculap ag , tuttlingen , germany ) , a plane mouth mirror ( aesculap ag ) and cotton rolls to remove any plaque or debris where necessary , and recorded on special charts .\nteeth were considered as decayed when in addition to showing clinical signs such as a color change , wedging and catching of an explorer tip during the examination of occlusal surface encountered some degree of resistance .\n, a surface is diagnosed as decayed if the explorer is retained . dressed and restored teeth that had recurrent caries\nteeth filled with temporary materials were considered as filled , and not as decayed ; no radiographs were taken .\nmissing teeth were not marked correspondingly , since no definite statement could be made without a proper anamnesis whether the tooth really existed , or if an early extraction had taken place . to assess the caries frequency\nthe dft index for the permanent dentition and the dft index for primary dentition were used , since it gives a good insight into the state of decay in the patient .\nif both the deciduous and permanent teeth were present , only the permanent teeth were evaluated . \n \n\nt - test was used to analyze the mean decayed and filled permanent / primary teeth ( dft / dft ) and the difference between groups , chi square test for evaluation of association between bmi - for - age and gender , and multiple linear regression for evaluation of association between bmi - for - age and dft / dft indices .\nthe authors certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research . \n\n\n the findings showed that 16% of the children were within normal weight range , 16.9% at risk of overweight , and 67.1% overweight .\nthere was no statistically significant association between bmi - for - age and gender ( p = 0.2 ) ( table 1 ) .\nthe mean se of dft in the normal weight , at risk of overweight and overweight groups were 0.34 0.08 , 1.23 0.13 and 0.73 0.05 , respectively ; and mean se of dft were 2.01 0.19 , 2.76 0.18 and 2.59 0.13 , respectively .\nmultiple linear regression showed that there was no statistically significant association between bmi - for - age and dft ( r = 0.06 ; ci : 0.01 to 0.09 ) , and bmi - for - age and dft ( r=0.07 ; ci : 0.003 to 0.046 ) . \n \n by taking the bmi - for - age into account , 27.7% of the children with normal weight were caries free , whereas only 14% of children at risk of overweight and 37.2% of the overweight children were caries free .\nthere was statistically significant association between bmi - for - age and being caries free ( p = 0.0001 ) . \n\n\n given the causative relation between refined carbohydrates and dental caries , it is appropriate to hypothesize that overweight might also be a marker for dental caries in children and teenagers .\nalthough bmi is widely used to screen adults for obesity , its use in adolescents is controversial .\nbmi is a commonly used measure of adiposity , because it is easy to calculate , quick to measure , and noninvasive .\nunfortunately , it is a fairly poor index in children unless age and gender are taken into consideration .\ntherefore , bmi - for - age categories were used in this study which might produce controversial results compared to the other studies .\nresults of the present study showed the high prevalence of overweight and at risk of overweight in the 6 - 11-year - old children in isfahan .\na study showed that prevalence of overweight was 20.8% in 3 - 9 year - old children according to bmi . \n \n\npalmer implicated that the relationship between obesity and caries in children needs further exploration ; it is clear that there are common denominators that both diseases share .\nnegative changes in eating and activity patterns , increased frequency of snacking and increased consumption of fermentable carbohydrates are common in both obesity and caries in children . \n \n\nthe mean dft / dft indices in the normal weight children were less than children at risk of overweight and the overweight .\nalthough it was hypothesized that bmi - for - age would be associated with increased dental caries prevalence , there was no association between bmi - for - age and dft / dft indices ( r 0.07 ) .\nthe relationship between nutrition and dental caries is complex because it is a multifactorial disease ; oral hygiene , available nutrients , saliva , and oral flora influence dental caries .\nchen et al investigated bmi index and dft score in three - year - old children .\nthey concluded that there were no significant differences in the dft score of carious children among different bmi groups and there is no relationship between carious deciduous teeth and weight status .\nkantovitz et al in a systematic review on the relationship between obesity in childhood found that only one study with high level of evidence showed direct association between obesity and dental caries .\nmacek & mitola concluded that there is no statistically significant association between bmi - for - age and dental caries prevalence for children in either dentition and overweight children with a positive history of dental caries in the permanent dentition exhibit fewer dmft than do their normal weight peers .\nthe authors found that overweight children aged 6 - 17 years had a significantly lower dental caries severity than did children of normal bmi - for - age . \n \n\nhilgers et al found that the mean caries average for permanent molars significantly increased with increased bmi , even after adjusting for age and gender .\nthey concluded that elevated bmi is associated with an increased incidence of permanent molar interproximal caries .\nburt & pai reported that children of low birth weight subsequently developed more caries in the primary dentition than did children with normal to high birth weight .\nthey concluded that this may be related to social deprivation factors during the development of the primary dentition .\nwillerhausen et al indicated a strong association of obesity and caries in 1290 children of elementary schools in a city in germany .\nanother study found that there was a significant correlation between the bmi and caries frequency even after adjustment for the age of the children .\none finnish study followed 516 children from birth to age 12 and used weight to predict caries experience ( dmft / dmft ) .\nthe investigators reported that obesity alone was not a very good predictor of dental decay . \n \n\nthe present study demonstrated a significant association between bmi - for - age and being caries free ( p = 0.0001 ) .\nthis is in line with the results of the study of willerhausen et al that showed number of healthy teeth decreased with age and bmi.a swedish study examined the relationship between dental caries and risk factors for atherosclerosis and reported that children with a dmft score greater than 9 had significantly higher bmi - for - age values than caries - free children . \n \n\nglick noted that , while the consequences of obesity will have an indirect effect on oral conditions , this alone is not justification to get involved .\nrather , there needs to be a stronger desire to have an impact on the patients general health .\nthese findings might also show that further investigation should be conducted to determine if an association exists between dental caries and bmi - for - age and to address what factors specific to overweight in children might be protective against dental caries especially in permanent dentition .\nthe future preventive programs must include strategies for nutrition control to avoid obesity as well as dental caries . \n\n\n there is a high prevalence of at risk of overweight and overweight in 6 - 11-year - old children in isfahan . at risk of overweight and overweight children\nhad higher dft / dft score than did normal children , but there was no association between bmi - for - age and dft / dft indices .", "answer": "background and aims \n childhood obesity has been associated with high refined sugar intake . \n the relationship between sucrose intake and development of dental caries has been established . \n the aim of this study was to determine the association between age - specific body mass index ( bmi - for - age ) and dental caries in children . \n \n materials and methods \n in this cross - sectional study a total of 1003 children were screened . \n weight , height , bmi - for - age and dental caries of 633 ( 317 boys , 316 girls ) 6 - 11-year - old children were clinically examined for dental caries using the world health organization criteria by a dentist on a dental chair . \n decayed and filled teeth ( dft / dft ) indices were used . \n bmi - for - age and dental caries were analyzed with multiple linear regression , chi - square , and t - tests using spss computer software . \n \n results \n the findings showed that 16% of the children had a normal weight , 16.9% were at risk of overweight , and 67.1% were overweight . in the normal weight , at risk of overweight , and overweight groups , the mean se for dft were 0.34 0.08 , 1.23 0.13 and 0.73 0.05 , respectively ; and 2.01 0.19 , 2.76 0.18 and 2.59 0.13 respectively , for dft . \n multiple linear regression showed that there was no statistically significant association between bmi - for - age and dft ( r = 0.06 ) and dft ( r = 0.07 ) indices . \n 27.7% , 14% and 37.2% of children with normal weight , at risk of overweight and with overweight were caries free , respectively . \n there was statistically significant association between bmi - for - age and being caries free ( p = 0.0001 ) . \n \n conclusion there was no association between bmi - for - age and dft / dft indices . \n in addition , a high prevalence of at risk of overweight and overweight was seen among 6 - 11-year - old children in isafahan , iran .", "id": 738} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nculicoides spp . latreille ( diptera : ceratopogonidae ) or biting midges are small ( 0.5 - 2.0 mm in length ) bloodsucking insects that have a broad distribution and impact on human and veterinary health as vectors of viruses ( bluetongue , african horse sickness , epizootic hemorrhagic disease of deer , akabane , aino , chuzan , and bovine ephemeral fever viruses ) , protozoan parasites ( haemoproteus and leucocytozoon spp . ) , and filarial worms ( onchocerca and dipetalonema spp . ) throughout their range [ 1 - 15 ] .\nthe first nationwide biting midge surveys in the republic of korea ( rok ) were reported in 1974 , with seasonal abundance and host blood meal analysis of culicoides spp . collected from cattle and poultry farms in gyeonggi - do ( province )\nmore recently , a brief summary of the history of research into the culicoides fauna and seasonal prevalence of culicoides spp . collected at 9 cowsheds in the southern part of the rok were reported by kim et al . along with new records of 3 culicoides spp .\n( c. nasuensis kitaoka , c. pallidulus yu , and c. jacobsoni macfie ) , bringing the total number of culicoides spp .\nvector - borne disease surveillance is conducted by the 65th medical brigade in collaboration with the public health command region - pacific ( phcr - pac ) to determine the species composition and seasonal and geographical distributions for mosquitoes and other biting flies , e.g. , culicoides spp . , and pathogens they harbor using mosquito magnet traps in / near the demilitarized zone ( dmz ) that separates north and south korea in northern gyeonggi - do , rok .\n, lititz , pennsylvania , usa ) use counter - flow technology and propane gas to produce heat and co2 as attractants to capture mosquitoes and other biting flies , such as culicoides .\ncollections were made at 4 sites , including the neutral nations supervisory commission ( nnsc ) camp ( 37 57 ' 16.39 \" n , 26 40 ' 50.03 \" e ) , daeseongdong village ( 37 56 ' 26.92 \" n , 126 40 ' 37.42 \" e ) inside the 2-km wide demilitarized zone ( dmz ) and adjacent to the military demarcation line ( mdl ) that separates north and south korea and at warrior base , a us army training site ( 37 55 ' 17.01 \" n , 126 44 ' 30.22 \" e ) , and a beef farm at tongilchon ( 37 54 ' 32.18 \" n , 126 44 ' 01.88 \" e ) located north of the imjin river and approximately 3 km from the dmz , gyeonggi - do , rok , from may - october 2010 - 2012 ( fig .\ndaeseongdong is a village of approximately 200 residents that is under the protection of south korea and is approximately 100 - 200 m from the mdl .\nrice farming is the principal activity , with an enclosed ( not pastured ) beef farm of < 50 cattle .\nthe mosquito magnet was placed at the northern most edge of daeseongdong and approximately 100 m north of the beef farm .\nwarrior base is a us military training site approximately 3 km south of the dmz .\ntongilchon is a small village of approximately 200 residents with 2 enclosed ( not pastured ) beef farms of approximately 50 cattle each .\nit is located approximately 2 km west of warrior base and 3 km from the dmz .\nthe mosquito magnet was placed outside one of the beef farms adjacent to a rice paddy and dry land vegetable farming .\nmosquito magnet traps were operated continuously , with specimens collected twice weekly from may - october in 2010 - 2012 .\nspecimens were transported to the 5th medical detachment , us army garrison , yongsan , seoul , rok , where mosquitoes and other biting flies were separated .\nspecimens of culicoides were transferred into 70% ethanol and identified using the keys of arnaud and the checklist of bellis et al . .\nvoucher specimens were submitted to the northern territory quarantine insect collection ( ntqic ) in darwin , northern territory , australia , for future reference and genetic studies .\na total of 18,677 culicoides females ( 18,399 ; 98.7% ) and males ( 248 ; 1.3% ) comprising 16 species were collected from may - october over a 3-year period from 2010 - 2012 .\nculicoides nipponensis tokunaga was the most commonly collected species ( 42.9% ) , followed by culicoides erairai kono and takahasi ( 29.2% ) , culicoides punctatus ( meigen ) ( 20.3% ) , culicoides arakawae ( arakawa ) ( 3.3% ) , c. pallidulus ( 1.8% ) , and culicoides circumscriptus kieffer ( 1.4% ) , while the remaining 10 species accounted for only 1.1% of all culicoides spp .\ncollected ( table 1 ) . c. nipponensis was the most frequently collected species ( females and males ) at daeseongdong village ( 67.1% ) , and was commonly collected from the nnsc camp ( 35.6% ) , tongilchon ( 33.9% ) , and warrior base ( 19.5% ) . c. erairai was the\nmost frequently collected species at nnsc camp ( 53.6% ) and accounted for 85.1% of c. erairai collected at all 4 sites ( table 1 ) , while c. punctatus was the most frequently collected species at both tongilchon ( 54.4% ) and warrior base ( 28.7% ) . c. nipponensis females demonstrated bimodal capture rates , with large numbers collected during may ( 1,754 , 82.4% ) , june ( 1,479 , 29.5% ) , and then again during september ( 3,332 , 81.7% ) ( table 2 ) .\nc. erairai was more frequently collected during june ( 2,962 , 59.2% ) and july ( 2,154 , 76.0% ) followed by a sharp decline in numbers collected from august - october . c. punctatus was collected infrequently from may - september ( range , 84 - 372 ) with large numbers only collected during october ( 2,756 , 88.0% ) .\noverall , low numbers of c. nipponensis were collected during 2011 , while higher numbers were observed during may - june and again during september 2012 at the nnsc camp and daeseongdong ( fig .\n2 ) . c. erairai was collected more frequently at the nnsc camp during the months of june - july 2011 and 2012 , with few collected from august - october for either year .\nlow numbers of c. punctatus were collected from may - september , with a sharp increases in numbers observed primarily at the beef farm at tongilchon during october for both 2011 and 2012 .\nthis is the first report for collections of culicoides using mosquito magnet traps that use only heat and co2 as attractants .\nthe addition of other chemical attractants , e.g. , octenol , has been shown to repel some species of culicine mosquitoes , while enhancing the collection of others , but the relative attractiveness of this attractant has not been investigated for most species of culicoides .\na major difference between mosquito magnet and light traps is that mosquito magnet traps operate continuously without bias toward nocturnal and diurnal active species .\nthis difference , however , indicates that comparative analysis between data obtained from mosquito magnet and light traps should be viewed with caution .\nbiting midges are both nuisance biters and vectors of medical and veterinary important pathogens that impact the economy of the animal industry in the rok . c. nipponensis , and c. punctatus were the most commonly collected species by mosquito magnets during this study and\nhave been associated with the transmission of important livestock pathogens , e. g. , fukuoka , aino , and ibaraki viruses , or as biting pests of humans ( c. erairai ) .\nconsequently , surveillance of these and other species of culicoides and associated pathogens are an important part of the veterinary health service to identify relative vector populations , their distributions throughout the rok , and the presence and prevalence of pathogens affecting livestock and poultry .\nthe dominance of c. nipponensis and c. punctatus in the mosquito magnet collections is similar to findings by cho and chong and kang and yu using new jersey light traps . similarly , lee found that c. punctatus , c. arakawae , and c. tainanus kieffer were the most commonly collected species at inland sites , whereas c. nipponensis and c. sinanoensis tokunaga were the predominant species collected from the south and eastern coastal areas in the rok .\nrecently kim et al . found that c. punctatus and c. arakawae were the dominant species collected from light traps set in 9 cowsheds in the southern part of the rok .\nthe unprecedented predominance of c. erairai and relatively low numbers of c. arakawae in the mosquito magnet traps compared to these and other previous reports may reflect the relative attraction of these species to light and the attractants associated with the mosquito magnet traps .\nthe dominance of c. nipponensis and c. punctatus at a cowshed at tongilchon agrees with the host preference of these species for cattle .\nalthough c. arakawae appears to have a preference for feeding on birds , it also readily feeds on cattle , which would explain its abundance around cowsheds in other reports but not the low numbers collected at the cowshed at tongilchon in this survey .\nthe variable distribution of culicoides spp . over a limited area ( 2 km radius ) demonstrates the focal species abundance due to little understood environmental and host attraction factors .\nfor example , high numbers of c. erairai were observed at the nnsc camp where humans are believed to be the primary host , while c. nipponensis was the primary species collected at daeseongdong and tongilchon where a variety of hosts ( e.g. , cattle , dogs , large water birds , and humans ) serve as potential hosts .\nthus , further studies comparing light and mosquito magnet traps and range of available hosts may reveal differential attraction for different species and assist in surveys targeting particular species .\nadditionally , studies on the geographical and seasonal distributions , host attraction ( e.g. , placement of traps near human habitation and poultry , cattle , and swine farms ) , temporal biting activity , pathogen infection rates , and their role as potential vectors of zoonotic pathogens that impact on human and animal health are warranted .\nalthough limited , the data presented herein provide a better understanding of the biology , ecology , and environmental parameters that affect relative population abundance of culicoides spp .\nthat can be used to predict potential human and animal health risks and develop and implement mitigation strategies .", "answer": "biting midges ( culicoides : ceratopogonidae ) were collected by mosquito magnet traps at the neutral nations supervisory commission ( nnsc ) camp and daeseongdong village inside the demilitarized zone ( dmz ) and near the military demarcation line ( mdl ) separating north and south korea and at warrior base ( us army training site ) and tongilchon 3 km south of the dmz in northern gyeonggi province , republic of korea ( rok ) , from may - october 2010 - 2012 , to determine their seasonal distributions . \n a total of 18,647 culicoides females ( 18,399 ; 98.7% ) and males ( 248 ; 1.3% ) comprising 16 species were collected . \n overall , the most commonly collected species was culicoides nipponensis ( 42.9% ) , followed by c. erairai ( 29.2% ) , c. punctatus ( 20.3% ) , c. arakawae ( 3.3% ) , c. pallidulus ( 1.8% ) , and c. circumscriptus ( 1.4% ) , while the remaining 10 species accounted for only 1.1% of all culicoides spp . \n collected . \n the seasonal distribution of c. nipponensis was bimodal , with high numbers collected during may - june and again during september . \n c. erairai was more frequently collected during june - july , followed by sharply decreased populations from august - october . c. punctatus was collected in low numbers from may - september with high numbers collected during october . c. erairai was predominantly collected from the nnsc camp ( 85.1% of all c. erairai collected ) located adjacent to the mdl at panmunjeom in the northernmost part of gyeonggi - do ( province ) , while other sites yielded low numbers of specimens .", "id": 739} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsodium - glucose cotransporter 2 ( sglt2 ) inhibitors are oral hypoglycemic agents that augment the urinary excretion of glucose , thereby regulating glycemic control and promoting weight loss ( 1 ) .\nsglt2 inhibitors have an insulin - independent mechanism of action , which is being explored in patients with type 1 diabetes ( 2 ) .\nthe incidence of diabetic ketoacidosis in patients treated with sglt2 inhibitors is rare ( 4,5 ) .\nrecently , the us food and drug administration issued a drug safety communication that sglt2 inhibitors may lead to ketoacidosis with mild to moderate glucose elevation ( euglycemic diabetic ketoacidosis ) ( 6 ) .\nhowever , only a few cases of euglycemic diabetic ketoacidosis with persistent diuresis after the discontinuation of sglt2 inhibitors have been reported .\nwe herein report a case of euglycemic diabetic ketoacidosis with persistent diuresis in a diabetic patient undergoing treatment with an sglt2 inhibitor , canagliflozin .\na 27-year - old woman of asian descent from north america was admitted to our hospital for the treatment of euglycemic diabetic ketoacidosis .\nshe had been taking oral antidiabetic drugs ( gliclazide 300 mg , metformin 3,000 mg , and sitagliptin 150 mg per day ) , but her glycemic control was poor .\nthree months prior to admission , she started taking canagliflozin ( 300 mg / day ) . during that time , she lost 3 kg and her urinary frequency increased .\ntwo days before admission , she experienced dizziness , and the following day , she developed upper abdominal pain .\non the day of admission , she visited the emergency department with complaints of thirst and malaise .\nshe did not smoke or drink alcohol , and she followed carbohydrate restriction for weight loss . on examination ,\nthe patient 's blood pressure was 145/103 mmhg , her heart rate was 123 beats / min , and her temperature was 36.2. her weight , height , and body mass index were 63 kg , 150 cm , and 28 kg / m , respectively .\nthe other neurological and general examination results were normal . a urinalysis detected ketone bodies , while an arterial blood gas analysis showed high anion gap metabolic acidosis and a normal lactate level .\nher biochemistry results revealed electrolyte disturbance and mild hyperglycemia ( 240 mg / dl ) .\nin addition , her hba1c level was 9.9% , and her fasting serum c - peptide level was < 0.1 ng / ml ( reference range , 0.61 - 2.09 ng / ml ) ; this finding indicated the severe impairment of insulin secretion .\ntaken together , these findings were compatible with a diagnosis of type 1 diabetes mellitus and diabetic ketoacidosis without hyperglycemia .\ncpr : c - peptide immunoreactivity , gad : glutamic acid decarboxylase , hba1c : glycated hemoglobin , pco2 : partial pressure of carbon dioxide , po2 : partial pressure of oxygen \n the patient was initially administered isotonic saline and a continuous insulin infusion with the discontinuation of all oral antidiabetic agents .\nan hour after the administration of saline and the insulin infusion , her glucose level decreased to < 200 mg / dl ; thus , an infusion 5% dextrose was initiated . on the following day ,\nher venous blood ph level still showed acidemia , despite a normal glucose level , and her urine output was > 5,000 ml / day .\n, oral food intake was initiated and the continuous insulin infusion was switched to multiple daily injections of insulin . at this point ,\nhowever , we prohibited ad libitum water intake . on day 4 of treatment , her venous blood ph level recovered , and her urinary output peaked ( figure ) . we could not measure the urinary output after the fifth day of treatment due to the discontinuation of urinary catheterization and the patient 's menstruation . on the eighth day of treatment , she was discharged but the nocturnal urination had not resolved .\nthe course of osmotic diuresis in a patient with euglycemic diabetic ketoacidosis who was treated with canagliflozin . on the second day of treatment\n, the patient s urine output increased to over 5,000 ml in the absence of hyperglycemia . on the third day of treatment , oral food intake\nwas initiated , and the patient s urine output increased to over 9,000 ml . at this point ,\ncvii : continuous intravenous insulin infusion , egfr : estimated glomerular filtration rate , fpg : fasting plasma glucose , mdi : multiple daily injections of insulin , na : not available , u - glucose : urinary glucose , u - osm : urine osmolality , serum na : serum sodium , u - na : urinary sodium\nsecond , euglycemic diabetic ketoacidosis can accompany persistent diuresis after the administration of sglt2 inhibitors is discontinued . to our knowledge , this is the first report of euglycemic diabetic ketoacidosis with persistent diuresis during treatment with an sglt2 inhibitor .\neuglycemic diabetic ketoacidosis is defined as a blood glucose level of < 300 mg / dl , and a plasma bicarbonate level 10 meq / l ( 7 ) . in a previous study of patients with type 2 diabetes ,\nthe incidence of diabetic ketoacidosis in patients treated with canagliflozin was more than twice as high as that in patients treated with antidiabetic drugs without canagliflozin ( 8) .\nonly a few case reports have described the characteristics of euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors .\nthe possible causative factors for euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors include an insulin dose reduction , alcohol intake , and a low insulin secretion capability .\ngastroparesis and a low - carbohydrate diet also can trigger euglycemic diabetic ketoacidosis , especially among diabetic patients who do not use insulin ( 9 - 12 ) .\nthe time from the first dose of an sglt2 inhibitor to the onset of euglycemic diabetic ketoacidosis has been reported to range from 2 to 13 days in diabetic patients who do not use insulin ( 9,11,12 ) . in the present case ,\nthere are several possible reasons for the patient 's development of euglycemic diabetic ketoacidosis , including her low adherence to treatment , the relatively acute autoimmune destruction of cells , and her extreme carbohydrate restriction .\nthis patient experienced euglycemic diabetic ketoacidosis with persistent diuresis via glycosuria , even after the discontinuation of the sglt2 inhibitor .\nthe possible mechanisms of this pathology are as follows : ( 1 ) her estimated glomerular filtration rate might have been increasing in association with early type 1 diabetes , thereby promoting glycosuria ; ( 2 ) exogenous insulin may have augmented the effect of sglt2 inhibition on glycosuria ( 13 ) ; and ( 3 ) canagliflozin delays the reversibility of sglt2 inhibition in comparison to its short half - life ( 10 - 13 hours ) . in a previous case ,\nburr et al . reported that their patient had persistent glycosuria in the absence of hyperglycemia for 11 days after the discontinuation of an sglt2 inhibitor ( 11 ) .\nthe correction of hypovolemia is important for the treatment of diabetic ketoacidosis ( 3 ) . in the present case ,\nthe patient received 3,650 ml of fluid in 12 hours of fluid therapy , which was reasonable from the point of view of treating diabetic ketoacidosis .\nafter the second day of admission , fluid therapy was administered according to her urine volume .\nthus , the volume of fluid that the patient received was appropriate for her clinical course . however , we did not rule out central diabetes insipidus .\nprevious studies have reported cases of central diabetes insipidus during diabetic ketoacidosis ( 14,15 ) . in our case ,\nthus , it remains unclear whether canagliflozin induced the patient 's osmotic diuresis or masked central diabetes insipidus .\nthe insulin - independent actions of sglt2 inhibitors are associated with short - term tolerability and the enhancement of urinary glucose excretion in patients with type 1 diabetes ( 2 ) . on the other hand\n, off - label use of sglt2 inhibitors in patients with type 1 diabetes sometimes leads to euglycemic diabetic ketoacidosis ( 6,9 ) .\nin addition , sglt2 inhibitor - treated type 2 diabetes patients who develop euglycemic diabetic ketoacidosis are often misdiagnosed as having autoimmune diabetes ( 8) . the possible pathophysiologic characteristics of euglycemic diabetic ketoacidosis due to sglt2 inhibitors are as follows : ( 1 ) the urinary glucose excretion of patients with euglycemic diabetic ketoacidosis due to the administration of sglt2 inhibitors is more prominent than that in patients with diabetic ketoacidosis ( 13 ) ; ( 2 ) sglt2 inhibitors inhibit the transportation of glucose into cells , thereby enhancing the release of glucagon , resulting in ketogenesis ; and ( 3 ) sglt2 inhibitors may augment the renal tubular reabsorption of ketone bodies ( 1 ) . in the present case ,\nthe patient 's intake of canagliflozin , the restriction of carbohydrates , and low insulin secretion capability led to euglycemic diabetic ketoacidosis .\nclinicians should therefore be cautious when prescribing sglt2 inhibitors to diabetic patients who restrict their intake of carbohydrates or who display insufficient insulin secretion . in conclusion , the diuresis of the present patient with euglycemic diabetic ketoacidosis persisted , even after the administration of the sglt2 inhibitor was discontinued .\nthe findings of this case emphasize that euglycemic diabetic ketoacidosis should be considered in sglt2 inhibitor - treated patients who develop nausea or fatigue .\nfurthermore , adequate hydration may enhance persistent diuresis via glycosuria in patients with euglycemic diabetic ketoacidosis who are treated with sglt2 inhibitors .", "answer": "diabetic ketoacidosis is characterized by hyperglycemia , anion - gap acidosis , and increased plasma ketones . after the resolution of hyperglycemia , \n persistent diuresis is rare . \n we herein report the case of a 27-year - old asian woman with type 2 diabetes who was treated with a sodium - glucose cotransporter 2 ( sglt2 ) inhibitor ( canagliflozin ) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia . \n physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with sglt2 inhibitors .", "id": 740} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\non february 13 , 1996 , a 7-year - old boy from doihue in administrative region vi was admitted to the hospital clnico fusat of rancagua in the region ( figure 1 ) with a 2-day history of adynamia and dizziness . on admission ,\n, progressive paralysis developed that evolved to respiratory failure ; the boy was connected to a mechanical ventilator .\ncat scan showed diffuse cerebral edema , and the electroencephalogram indicated no electric activity . intracranial hypertension developed , and the patient\nmap of south america showing the geographic position of chile and map of chile presenting the geographic distribution of the administrative regions of the country .\na virus was considered the most probable cause , laboratory tests were conducted to determine the presence of the following viruses : herpes , measles , coxsackie , echo , and polio .\ninterviews with relatives and the boy s nanny revealed that bats had been observed in the family s house .\nthe nanny also reported that she had seen a bat flying away from the child s toy box . even though these interviews failed to reveal any direct contact with bats or any history of an animal bite , this epidemiologic information prompted the physicians to suspect rabies . on february 26 , 1996\n, a serum sample and corneal smear were obtained from the patient and sent to the rabies laboratory of the instituto de salud pblica de santiago ( isp ) .\na rabies antibody titer of 1:625 was found in the serum specimen by using the indirect fluorescent - antibody ( ifa ) technique ( 14 ) .\nthe patient had no history of rabies vaccination to account for the presence of antibodies .\nthe corneal smear was negative for rabies antigen by the direct fluorescent - antibody ( dfa ) assay ( 15 ) . on march 4 , a second serum sample ,\nthe second serum sample was tested simultaneously with the first one by ifa assay , and a titer of 1:15,625 was detected .\nthe saliva sample was negative by dfa assay and suckling mouse inoculation ( 15,16 ) .\nthe patient died on march 5 , 1996 , when artificial respiratory support was disconnected .\npostmortem tissue samples of cerebral cortex , hippocampus , cerebellum , and nuchal skin biopsy were sent to the isp rabies laboratory for diagnosis .\nrabies postexposure prophylaxis with the suckling mouse brain fuenzalida - palacios vaccine was administered to the victim s mother and to 10 health - care providers who had possible contact with the patient s saliva .\nthe rabies postexposure prophylaxis schedule used was 2 ml of vaccine , subcutaneously , on each of days 1 , 2 , 3 , 4 , 5 , 6 , 21 , and 90 .\nblood samples were taken from vaccinees on day 14 after the initial dose of vaccine ; ifa assay showed that adequate immune responses had developed .\nthe virus was isolated from the patient s brain tissue by intracerebral inoculation of suckling mice ( 16 ) . to help identify the possible source of infection , the virus was antigenically and genetically characterized .\nantigenic characterization of the virus was carried out by using a panel of eight monoclonal antibodies directed against the viral nucleoprotein , provided by the centers for disease control and prevention .\nthese analyses identified a rabies antigenic variant associated with tadarida brasiliensis ( free - tailed bat ) in chile , which had been designated as antigenic variant 4 ( agv4 ) ( 9,17 ) .\ngenetic characterization was done by sequencing a 320-bp portion of the rabies virus nucleoprotein gene from nucleotide position 1,157 to 1,476 , as compared with the sadb 19 strain ( 18,19 ) .\nbriefly , genomic viral rna was extracted from infected tissue by using trizol ( invitrogen , san diego , ca , formerly gibco - brl inc . ) according to the manufacturer s instructions .\ncomplementary dna was produced by a reverse transcription polymerase chain reaction with primers 10 g and 304 ( 19 ) and was sequenced by using the taq big dye termination cycle sequencing ready reaction kit ( applied biosystems , foster city , ca ) , according to the manufacturer s protocol , on an applied biosystems 377 dna automated sequencer ( applied biosystems ) .\nthis human rabies virus isolate was compared with viruses obtained from domestic animals and insectivorous bats in urban centers in chile from 1977 to 1998 ( 18 ) .\npileup and pretty programs of the wisconsin package , version 10 ( genetic computer group , 2000 , madison , wi ) , were used to produce sequence alignments and comparative nucleotide analyses .\nthe programs dnadist ( kimura - two parameter ) , neighbor ( neighbor - joining method ) , and dnapars ( parsimony method ) from the phylip package , version 3.5 ( 20 ) , were used in the phylogenetic studies .\nthe bootstrap method , as implemented by the seqboot program from phylip , was followed by the use of dnadist and neighbor for the distance matrix analyses .\nalthough five genetic variants of rabies virus are found in chile ( 18 ) ( figure 2 , groups a to e ) , a reservoir has been identified for only two : t. brasiliensis ( figure 2 , group d ) and lasiurus sp .\nphylogenetic analyses of the chilean human isolate demonstrated that it segregated in group d. this group represents the genetic variant of rabies virus most frequently isolated throughout the country , formed by viruses from the metropolitan region and regions iv , v , vi , vii , viii , ix , and x ( figure 1 ) .\nthe high bootstrap value that supports the inclusion of this virus in group d and the very close genetic relationship it has with the other members of this group ( average genetic distance 0.5% ) clearly show that t. brasiliensis is the likely reservoir of the rabies virus isolated in this case .\nneighbor - joining tree comparing the human rabies isolate with representatives of the rabies genetic variants obtained from insectivorous bats and domestic animals in chile ( 18 ) .\nbootstrap values obtained from 100 resamplings of the data by using distance matrix ( top ) and parsimony methods ( bottom ) are shown at nodes corresponding to the lineages representing the rabies virus variants ( a , b , c , d , and e ) currently circulating in chile . only bootstrap values\nduvenhage virus , genbank accession number , european bat lyssavirus , myotis chiloensis , roman numerals indicate the administrative region where the sample was obtained , tadarida brasiliensis , metropolitan region , lasiurus borealis .\nthe absence of a history of an animal bite , the clinical presentation of the disease without the classic signs of hydrophobia or aerophobia , and the absence of any human rabies cases for a period of 24 years in chile were the primary reasons that rabies was not first suspected and a definitive diagnosis was delayed in this case .\nretrospective studies of human rabies epidemiology have demonstrated that it is not uncommon to observe rabies cases in which there is no history of a bite , mainly in situations involving insectivorous bat rabies variants .\nfor example , of the 17 human rabies cases associated with insectivorous bats reported in the united states from 1980 to 1996 , only one had clear documentation of a bite ( 22 ) . without proper education , patients may not be aware of the risks from a bat bite .\nmoreover , the wound may not be appreciated as a concern because of the limited injury inflicted by the bat 's small teeth ( 23 ) .\nfinally , there may not be an opportunity to obtain a history from a pediatric patient or to discern an exposure that occurs during sleep or other circumstances ( 24 ) . in cases in which a patient shows clinical signs of central nervous system involvement of unknown or suspected viral origin\n, health - care providers should be aware of the importance of conducting a thorough medical history to appropriately assess the possibility of rabies . with the important changes in the epidemiologic patterns of rabies in latin america , this disease\nshould be included in the differential diagnosis of neurologic diseases characterized by acute encephalitis and progressive paralysis , even when no previous history of an animal bite exists and even in regions where canine rabies has been eradicated .", "answer": "the first human rabies case in chile since 1972 occurred in march 1996 in a patient without history of known exposure . \n antigenic and genetic characterization of the rabies isolate indicated that its reservoir was the insectivorous bat tadarida brasiliensis . \n this is the first human rabies case caused by an insectivorous bat rabies virus variant reported in latin america .", "id": 741} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nelastosonography is an ultrasound based diagnosis which measures the elasticity or stiffness of the tissue .\ncompressibility of the tissue is a parameter evaluated by an elastogram and it is expressed as the change in tissue displacement as a function of its distance from the probe which is recognised as strain . among the 400450 lymph nodes ( lns ) of the human body , 6070 are located in the head and neck area .\nlns display reactive enlargement in infection and also when they are primarily or secondarily involved in malignancies of head and neck .\nan important criterion is the hardness of the ln , because lns might demonstrate increased stiffness on the elastogram if affected by a malignant process [ 24 ] .\nthe purpose of this study is to determine the reference sonoelastography values of cervical lns .\nafter obtaining the approval of the ethical committee , patients referred to the radiology department for cervical vascular doppler ultrasonography examination from january to march 2013 were enrolled in this prospective study .\n97 cervical lns of 89 consecutive patients ( 70 lns in 64 females , 27 lns in 25 males ; mean age 54 years old ; age range , 2184 years ) who were referred to our clinic for the examination of cervical vasculature were analysed by elastosonography .\none radiologist with 20 years of conventional sonography and 5 years of elastosonography experience performed the examination .\nthe scanner used was esaote gold platform mylab 60 ( italy ) equipped with elasto software ( elaxto ) .\nb - mode images were first obtained for each ln . afterwards elastosonography was performed by applying light vertical pressure followed by decompression until a good quality image was obtained .\nelaxto software also made the sonographer aware of the compression degree by the help of its unique optimal compression scale for measurement .\nreal time b - mode and elastosonographic images were demonstrated next to each other on the screen .\na region of interest ( roi ) box was placed in the ln taking the adjacent subcutaneous fat tissue as the reference .\ndepth , length , width , length to width ratio , hilar thickness , and cortical thickness of the lns were measured .\nlns with cortical thickness less than half of its hilar thickness were categorised as group a , and lns with cortical thickness equal to or more than half of the hilar thickness were categorised as group b. first strain ratio ( sr ) of the lns was measured .\nafterwards , elastographic images were given 1 of 4 elasticity scores ( ess ) based on the percentage of stiff areas modified from choi et al . which was introduced for the differential diagnosis of axillary lns in breast cancer .\nes 1 ( figure 1 ) , an absent or a very small red area ( i.e. , stiff ) ; es 2 ( figure 2 ) , small , scattered red areas , total red area < 45% ; and es 3 ( figure 3 ) , large red area , total red area 45% ; and es 4 ( figure 4 ) , red area occupying the entire ln , were the classifications used in the study .\n64 ( 66% ) of the lns were found on the right side and 33 ( 34% ) were found on the left side of the neck .\nthe mean size of the lns was 17 mm with a range of 628 mm .\nthe mean depth of the lns was 11 mm , with a range of 519 mm .\n18 lns ( 18.6% ) were categorised as group a. 79 lymph nodes ( 81.4% ) were categorised as group b. 67 lns ( 69.1% ) had sr less than 3 and were categorised as group 1 .\n30 lns ( 30.9% ) with sr equal to or more than 3 were categorised as group 2 .\n32 lns ( 33% ) displayed es 1 ; 30 lns ( 30.9% ) demonstrated es 2 ; 22 lns ( 22.7% ) showed es 3 ; 13 lns ( 13.4% ) had es 4 .\n62 lns ( 63.9% ) with scores 1 and 2 were assigned as es grade 1 ; 35 lns ( 36.1% ) having scores 3 and 4 were assigned as es grade 2 .\nthere was a statistically significant correlation between thickness ratio groups and elasticity score grades ( p : 0.011 ) .\na statistically significant correlation was also demonstrated between sr groups and elasticity score grades ( p : 0.000 ) .\nelastosonography , a noninvasive imaging modality , can potentially help the differentiation of benign and malignant lns by reducing the number of unnecessary biopsies . in the literature ,\nseveral studies have been published for the sonographic diagnosis of metastatic cervical lns by b - mode [ 610 ] .\nb - mode criteria for evaluating superficial lns are size , shape , the presence or the absence of the hilum , ratio of the cortex to hilum , borders , echogenicity , and homogeneity of internal structures . however\nno single ultrasonography criterion for malignant lns had high sensitivity and specificity [ 11 , 12 ] .\nspecific criteria to differentiate reactive and metastatic cervical lns are still not well established . a simple , reproducible , noninvasive imaging technique for diagnosis of malignant lns is necessary .\nsohn et al . investigated the b - mode criteria to differentiate metastatic lns from benign lns taking fine needle aspiration biopsy as the gold standard .\nthey evaluated the diagnostic performance of each ultrasound feature ( loss of fatty hilum , presence of cystic change or calcification , hyperechogenicity , and round shape ) .\nthey concluded that the most accurate ultrasound criterion to differentiate metastatic from benign lymph nodes was the presence of one of these malignant ultrasound findings , excluding the loss of fatty hilum .\nthe 5-point elasticity scoring system was introduced by itoh et al . for breast lesions .\npublished their results in the diagnosis of cervical ln metastasis using gray - scale sonographic elastography .\nthey utilized a 4-point scale including visibility , relative brightness , margin regularity , and margin definition of the ln .\nthey measured strain index of the lns by comparing the absolute strain values of the lymph nodes with the absolute strain values values of the nearby muscles .\nstrain index greater than 1.5 was the most useful criteria in metastatic ln classification , having 98% specificity , 85% sensitivity , and 92% accuracy . \nalam et al . used a 5-pattern color scoring system based on distribution and percentage of area with high elasticity in the cervical lns .\nthe cut - off line for reactive versus metastatic lns was set between patterns 2 and 3 ; patterns 35 were considered metastatic .\nthey evaluated the sum of scores of five criteria , that is , short - axis diameter , shape , border ( regular or irregular ) , echogenicity ( homogeneous or inhomogeneous ) , and presence or absence of hilum for b - mode diagnosis .\nthe cut - off line for reactive versus metastatic was set between scores 6 and 7 .\nsensitivity , specificity , and accuracy of b - mode sonography were 98% , 59% , and 84% , respectively ; 83% , 100% , and 89% for elastography ; and 92% , 94% , and 93% for the combined evaluation .\nthey concluded that the combination of elastography and b - mode sonography has the potential to improve the diagnosis of metastatic enlarged cervical lns .\nconcluded that elastosonography had 93.8% sensitivity and 89.5% specificity in the differentiation of benign and malignant cervical lymph nodes . in a meta - analysis of the real - time elastography for the differentiation of benign and malignant superficial lns ying et al . concluded that even though es measurement had a good diagnostic accuracy , it had significant interobserver variability\nthus , a quantitative method such as strain ratio measurement was needed for analysis of elasticity of the ln .\nalthough the accuracy of strain ratio measurement was similar to es measurement , it improved the diagnostic sensitivity value .\ntheir meta - analysis suggested that real - time elastography could be used as a good identification tool for malignant lns . \nnevertheless only a limited number of studies have been carried out to determine the elasticity of various tissues .\nlevinson et al . evaluated the elasticity of skeletal muscles and arda et al .\nconducted a study to determine the elasticity values of normal soft tissue including thyroid , parotid , and submandibular glands , gastrocnemius and masseter muscles , supraspinatus and achilles tendons , renal cortex , and pelvis , spleen , and pancreas of healthy volunteers .\nestimation of tissue elasticity is useful for characterization of normal tissue . to our knowledge , the normal elasticity values of cervical lymph nodes have not been studied so far . in our study 36.1% of the evaluated cervical lns\nthe aim of elastography is not necessarily to diagnose malignancies but to help reduce the number of unnecessary biopsies for benign processes by determining soft versus hard tissues due to its high specificity [ 2 , 3 , 19 ] .\nelastosonography is a user dependent technique closely related to experience . due to the shape of the neck ,\nthe pulsations from the neighboring great vessels may also make it difficult to obtain good quality elastograms .\nthe primary aim of this research was to determine the reference values of cervical lns to guide elastographic studies not to establish the benign versus malignant nature of the lymph nodes .", "answer": "background . it is crucial to differentiate between reactive and malignant lymphadenopathies . \n elastosonography measures the elasticity of the tissue . \n having a reference value for benign lymph nodes ( lns ) is important in interpretation . \n the purpose of this study is to determine the reference elastosonography values of cervical lns \n . methods . \n 97 lns were evaluated by b - mode and elastosonography . \n depth , length , width , length to width ratio , hilar - cortical thickness , strain ratio , and elasticity scores were measured . \n results . in 18.6% of the cervical lns cortical thickness was less than the hilar thickness ( group a ) and in 81.4% it was equal or more ( group b ) . \n 69.1% of lns showed strain ratio ( sr ) less than 3 ( group 1 ) and 30.9% equal to or more than 3 ( group 2 ) . \n 33% of lns displayed elasticity score ( es ) 1 ; 30.9% es 2 ; 22.7% es 3 , and 13.4% es 4 . \n there was a significant correlation between thickness ratios and elasticity scores ( p : 0.011 ) . \n a significant correlation was also demonstrated between sr groups and elasticity scores . \n conclusion . a simple , reproducible , noninvasive imaging technique for diagnosis of malignant \n lns is necessary . \n elastosonography can aid in the differentiation of benign versus malignant cervical lns , thus help reduce the number of unnecessary biopsies for benign processes .", "id": 742} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nstandard care for chronic hepatitis c ( chc ) has been a combination of pegylated interferon - alpha ( peg - inf ) and ribavirin , although this treatment has suboptimal antiviral efficacy and significant adverse events . even in the latest treatment recommendation using novel direct acting antiviral agents , interferon ( ifn)-based treatments are still optional .\nthe main drawbacks of interferon - based treatment are unsatisfactory response rate and various adverse effects , which often lead to premature termination of treatment followed by treatment failure .\nmyasthenia gravis ( mg ) is an autoimmune neuromuscular junction disorder characterized by muscular weakness and fatigability .\nmg is occasionally associated with invasive thymoma that needs surgical resection and may progress to severe respiratory failure .\ndevelopment of mg in patients with chc has been rarely reported before or during antiviral treatment with interferon .\na total of 12 cases of mg were reported in association with interferon treatment for chc and 6 of them went through myasthenia crisis that require respiratory support .\nwe experienced a rare case of myasthenia crisis during antiviral therapy for chc , in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care .\nwe reviewed the clinical course of this life - threatening complication of ifn treatment along with the already reported myasthenia crisis cases in chc patients .\na 47-year - old male patient presented with a complaining of sudden diplopia that developed one week after 11-week of antiviral combination treatment for chronic hepatitis c ( figure 1a ) .\nhe had been on antiviral combination treatment with peg - ifn-2a ( 180 g / wk ) ( pegasys ; roche , basel , switzerland ) and ribavirin ( 1000 mg / d ) ( lg ribavirin ; lg life sciences , seoul , korea ) for the genotype 1b hepatitis c virus ( hcv ) infection .\nthe pretreatment serum hcv rna level was 2.32 10 iu / ml and ast / alt levels were 255/323 u / l . at 6-week of treatment ,\nthe dosage of peg - ifn-2a was reduced to 90 g / wk , but wbc count continued decreasing to 2000/mm .\nfive weeks later , the absolute neutrophil count was 500/mm and the serum hcv rna level was below the limit of detection ( < 15 iu / ml ) .\nconsequently , the antiviral treatment was promptly discontinued and the neutropenia improved on serial blood tests .\none week after discontinuation of antiviral treatment , the patient complained of sudden diplopia and right eye ptosis was observed .\none week later , right eye ptosis and upper extremities weakness ( grade iii ) were noted . he was immediately hospitalized and initial physical examination was normal except facial palsy with the right ptosis , mild dyspnea , and upper extremities weakness . upon admission , he denied any other oral medications and had no history of vascular or thyroid diseases .\nptosis and restricted movement on the right upper lid was improved after treatment ( b ) .\non further evaluation , the low rate repetitive nerve stimulation test ( jolly test ) and neostigmine test were positive findings for myasthenia gravis ( table 1 ) and serum antiacetylcholine receptor ( anti - achr ) antibody level of 14.95 nmol / l ( normal range : below 0.2 \ninitial symptoms of ocular mg progressed to difficulties in chewing and swallowing , followed by respiratory failure in 3 days .\nadministration of pyridostigmine ( mestinon ) 180 mg / day was started and chest ct scan was performed which revealed anterior mediastinal mass measuring 7 cm in its greatest dimension , whereas brain imaging study was normal ( figure 2 ) .\nthe patient received a surgical thymectomy and a high - grade thymoma invading pericardium and pleura ( figure 3 ) was observed on the pathological examination of the surgical specimen , which confirmed invasive thymoma ( type b3 , who classification ) .\nthe patient 's respiratory failure aggravated after surgery , leading to an increased ventilator dependency . in response to the worsening respiratory condition\n, pyridostigmine dose was increased up to 600 mg / d and intravenous immunoglobulin and high - dose steroid pulse therapy were started .\nafter 40 days of intensive care , the patient has his ocular symptoms back to normal ( figure 1b ) and was successfully weaned from the mechanical ventilator .\nresults of low rate repetitive nerve stimulation test ( rnst ) and stigmine test chest ct findings .\nthere was 7-cm sized lobulated solid mass with internal low density and calcified portion at anterior mediastinum .\n( a ) h&e stain ( 40 ) shows a multilobular growth pattern and infiltration into lung parenchyma .\n( b ) h&e stain ( 100 ) shows thymoma b3 findings : sheet - like growth of medium - size round or polygonal cells with slight atypia ( sheet - like growth pattern ) ; epithelial cells are mixed with a minor component of intraepithelial lymphocytes .\ntreatment for chc with combination of peg - inf and ribavirin eradicates hcv rna in 40% to 50% of treatment - naive patients infected with hcv genotype 1 . in early clinical trials ,\n10% to 14% of treated patients discontinue combination treatment prematurely due to various adverse events and ifn was the major concern in most of them .\nunsatisfactory response rate and high rate of unbearable side effects have been the major issues of conventional combination therapy .\nrecently , direct acting antiviral agents ( daa ) against hcv were developed and showed markedly improved clinical efficacy than the conventional combination treatment in terms of both potency and safety aspects .\nnew standards of treatments using direct acting antivirals are being established and rapidly replacing the conventional combination therapy . however , the conventional combination treatment is still widely prescribed for chc and ifn is not completely excluded from some of the daa - based new regimens yet .\ntherefore , for the treatment of chc it is still major concern of clinicians to cope with the various side effects of ifn .\nmg in patients with chc were mostly associated with ifn treatment , but it may develop without ifn administration . two case reports described development of mg in chc patients who did not receive antiviral treatment . a 35-year - old male patients with established chc for several years without any treatment developed mg and a 59-year - old male with liver cirrhosis as a result of long - standing hcv infection developed typical mg symptoms and died due to myasthenia crisis .\nthe authors suggested the cross - reactivity between hcv epitopes and the acetylcholine receptor as the underlying mechanism .\nthe etiologic roles of various viral infections including hcv were suggested for the development of mg , but the exact significance of hcv infection per se is not clear .\nthough mg was not reported in large - scale analyses of chc patients who received ifn treatment , literatures suggesting the association between mg and ifn administration have been published in the form of case reports .\nthere were 12 cases of mg by ifn for chc including 6 myasthenia crisis cases ( table 2 ) . in case reports of myasthenia crisis that developed during ifn - based antiviral treatment for chc ,\nmale patients > 44 were most commonly affected and the mean age of patients was 57 years and mean interval between starting ifn administration and diagnosis of mg was 4.57 months ( 6 weeks to 15 months ) .\nthe mean duration of ifn treatment was 4.96 months ( 6 weeks to 15 months ) .\nthe mean level of anti - achr antibody was high as 16.3 nmol / l .\nin most patients , respiratory distress followed advanced progression of mg symptoms and a case of severe respiratory failure was reported at 6 months after ifn discontinuation .\nthe clinical courses of mg cases by ifn for chc were either mild or severe enough to suffer myasthenia crisis , but most of the patients were recovered eventually with medical care after discontinuing ifn treatment . list of cases of myasthenia crisis by interferon treatment for chronic hepatitis c to our knowledge , this is the second case of thymoma - associated mg during ifn treatment for chc . a case of mg that progressed to myasthenic crisis was reported at 1996 in japanese patient who had thymomectomy for known thymoma - associated mg , 19 years before starting antiviral treatment .\nthymomas are responsible for 21% of mg cases and 30% of patients with thymoma have symptoms of mg .\nmyasthenic crisis is the most serious complication of mg and thymoma is one of the risk factors attributed to it .\nthe mechanism of mg development by ifn therapy is not completely understood , but some of the complex immunological actions of ifn such as enhanced lymphocyte cytotoxicity , production of pro - inflammatory cytokines , inhibition of t suppressor cell function , activation of t helper lymphocytes by autoantigens , and differentiation of antigen - presenting cell might contribute to the development of ifn - induced autoimmune diseases .\nthe thymus plays a primary role in early - onset mg mediated by anti - achr antibodies\n. ifn - beta could play a central role in thymic events leading to mg by triggering the overexpression of a - achr probably leading to thymic dendritic cells autosensitization , the abnormal recruitment of peripheral cells , and germinal center formation .\nthe epithelial neoplastic cells of thymoma are capable of presenting epitopes , which cross - reacts with different neuromuscular antigens .\nin addition to achr antibodies , antibodies against striated muscle titin and ryr antigens are found in most of mg thymoma patients . on the other , it has also been suggested that some infectious viruses and hcv itself may lead to mg via mechanism of cross - reactivity between viral epitopes and the acetylcholine receptor .\nit is not known whether the patients who experienced mg during ifn treatment for chc had subclinical mg before initiating treatment because pretreatment screening for mg is not routinely recommended . in some patients ,\npre - existing subclinical mg that might be associated with hcv infection itself , progress to overt mg during ifn treatment , whereas , in others , de novo mg might be induced by ifn administration . in our patient , relatively large thymoma\nso it seems that thymoma - associated subclinical mg were unrecognized before treatment , which was provoked by ifn administration to progress to life - threatening myasthenic crisis . for the better understanding of clinical implication of ifn - induced mg in chc treatment , screening for mg in chc patient\nmight be considered before starting treatment or at least , during treatment when the patient complained of fatigue , muscle weakness .\nscreening for mg with serum anti - achr antibody test is simple and helpful in many patients , but it needs further investigation in this clinical condition because some of mg patients have serum anti - achr antibody levels within normal range .\nin patients with chc who is going to receive ifn - based antiviral treatment , whether screening for thymoma or subclinical mg should be included in basal evaluation is not clear but physicians need to keep in mind the potential life - threatening manifestations of mg before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability .", "answer": "abstractmyasthenia gravis is occasionally associated with thymoma that needs surgical resection and may progress to severe respiratory failure . \n we experienced a rare case of myasthenia crisis during antiviral therapy for chronic hepatitis c , in whom mediastinal thymoma was discovered and successfully managed with surgical thymectomy and meticulous medical care.a 47-year - old - male patient complained of sudden diplopia 1 week after stopping 11-week administration of pegylated - interferon and ribavirin for chronic hepatitis c. ophthalmologic examinations revealed ptosis on the right eyelid and restricted right eye movement . \n myasthenia gravis was confirmed by positive repetitive nerve stimulation test and positive serum antiacetylcholine receptor antibody test , and mediastinal thymoma was found on chest ct scan . \n the ocular myasthenia gravis progressed to respiratory failure even after discontinuing antiviral treatment but eventually recovered with thymectomy , anticholinesterase administration , steroid pulse therapy , and prolonged ventilator care . \n we describe the clinical features of this life - threatening complication of interferon treatment along with previous myasthenia crisis cases by interferon for chronic hepatitis c.in patients with chronic hepatitis c who is going to receive interferon - based antiviral treatment , physicians need to keep in mind the potential life - threatening manifestations of myasthenia gravis before and during antiviral treatment especially when patients complain of muscular weakness and easy fatigability .", "id": 743} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmyoepithelial carcinoma ( mc ) is a rare tumor with an incidence of 0.2% of all salivary gland tumors . most of the reported cases of mc arise in the parotid gland ( 4875% ) , followed by minor salivary glands , and the submandibular gland .\nthe first case was described by higashiyama et al . , in 1998 . since then , only seven cases have been reported in literature .\na mentally retarded 13-year - old girl , with a history of congenital hypothyroidism and cystic lymphangioma in the left dorsal region , operated in 2004 , had consulted for cough and dyspnea in september 2010 .\nphysical examination showed a decrease in vesicular breath sounds at the basal areas of chest bilaterally , without fever .\npulmonary computed tomography ( ct ) showed bilateral pleural masses measuring 6.3 cm and 7.4 cm at the right and left bases , respectively , with lymph node metastases [ figure 2 ] .\n( a ) bilateral pulmonary opacities ( b ) disappearance of pulmonary opacities pulmonary computed tomography ( ct ) : bilateral pulmonary masses a histopathological study of the left pleural biopsy revealed a monomorphic proliferation of round cells with clear cytoplasm and a weak , mitotic hyperchromatic oval nucleus [ figure 3 ] .\nthere were some cohesive layers , separated by bands of sclerosis ; the stroma was sparse with foci of necrosis .\nthe immunohistochemistry ( ihc ) study was focally positive for vimentin , cd99 , and ps100 .\nthe abdominal ultrasound , bone scan , and metaiodobenzylguanidine ( mibg ) scintigraphy were normal .\nthe histopathological and the ihc review at the institut bergoni in france concluded the diagnosis of myoepithelial carcinoma of the soft tissues with intermediate malignancy .\nihc was positive for pancytokeratin ( ae1/ae3 ) and ps100 , and negative for ema , cd34 , desmin , and cd99 .\nthe progression was marked by the disappearance of the pulmonary opacities [ figure 1 ] .\nthey include mucoepidermoid carcinoma , adenoid cystic carcinoma , acinic cell carcinoma , oncocytoma , epithelial \nit arises from the submucosal bronchial glands of the lower respiratory tract . in the world health organization classification , published in 2004 ,\nmc was cited as being synonymous with epithelial myoepithelial carcinoma . as mc and epithelial \nmyoepithelial carcinoma of the salivary gland are distinguished by the presence or absence of ductal cells , their pulmonary counterparts must also be differentiated .\nmyoepithelial tumors are low - grade lesions without recurrences or metastasis described after resection , whereas , the rate of metastasis in mc is high , as seen in our case .\nour patient represents the first pediatric case , described in the literature , having primitive pulmonary mc .\nthe tumor was peripheral and bilateral , measuring 6 cm and 7 cm , which was in agreement with the literature .\nin fact , the size of the mc ranged from 15 mm to 130 mm ( mean 50.7 mm ) [ table 1 ] . characteristics of pulmonary mc in our case , the histopathological study oriented to the diagnosis of a primitive neuroectodermal tumor or neuroblastoma .\nthe pathological review , with further ihc analysis in france , had concluded the diagnosis of mc .\nthe following markers were found to be useful in myoepithelial carcinoma : cytokeratins ( ae1/ae3 ) and vimentin ( reported to be positive in neoplastic myoepithelial cells and negative in normal myoepithelial cells ) .\nother variable markers , such as , ps100 , calponin , smooth muscle actin ( sma ) , muscle - specific actin ( msa ) , smooth muscle myosin , and p63 protein , could be positive .\nhowever , neoplastic transformation of myoepithelial cells could result in a loss or a modification of their smooth muscle phenotype . in our case ,\nalthough the eight patients reported in literature were treated with optimal surgery , metastases were reported in seven of them ( 87.5% ) ( contralateral lung , forearm , liver , and brain ) .\nit was significant that a patient who had not developed metastasis , had the lowest tumor mitotic rate of 5/10 hpfs .\nthis fact reasoned that the mitotic rate could be an important prognostic factor of the clinical outcome and survival in primary myoepithelial carcinoma of the lung .\ngiven the rarity of these tumors , recommendations regarding chemotherapy or radiation , either pre- or postoperatively , are difficult to formulate .\nthe originality of our case is the disappearance of the pulmonary opacity spontaneously , without any treatment .\nour case represents , to the best of our knowledge , the first pediatric case having primitive pulmonary mc .\nthe histopathological study familiarizes the diagnosis , but a further ihc study is needed to confirm the diagnosis and to eliminate other etiologies .\nsurgery represents the main treatment for the operable forms . to the best of our knowledge ,\nwe have reported the first case , with spontaneous regression of this tumor , without any treatment .", "answer": "primary myoepithelial carcinoma ( mc ) of the lung is exceedingly rare . \n we report here , to the best of our knowledge , the first pediatric case having primitive pulmonary mc . \n the originality of our case was the disappearance of the pulmonary opacity spontaneously , without any treatment . \n the difficulties in our case were the diagnosis of this rare entity and its subsequent treatment . \n in fact , given the rarity of these tumors , recommendations regarding chemotherapy or radiation , were difficult to formulate .", "id": 744} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nparosteal lipoma is an extremely rare benign tumor composed mainly of mature adipose tissue with a bony component .\nit is among the rarest neoplasias of skeleton , accounting for less than 0.1% of primary bone tumors and 0.3% of all lipomas .\nthe most common locations for this tumor are the femur , proximal radius , humerus , tibia , clavicle and pelvis .\nthought to arise from mesenchymal cells in the periosteum , parosteal lipomas share histopathologic features with the commonly occurring soft - tissue lipomas , and cytogenetic evidence suggests a common histopathogenesis . depending on the degree of chondroid modulation and enchondral ossification , parosteal lipomas may rest directly on the cortex without cartilage or bone elements ; may have a narrow bony stalk with a lucent lipomatous cap , mimicking a pedunculated exostosis ; may have a densely ossified broad - based osteochondromatous element beneath a thin lipomatous cap , simulating a sessile exostosis ; or may have patches of chondroid and bone scattered throughout the lipomatous mass .\nthis study reports the case of a 65-year old woman with a big mass on the posteromedial aspect of the right upper arm since 1 year ( admitted on 05/07/2013 ) .\nthe swelling was slow growing , painless , soft , nontender , immobile , with well defined margins and no fixity to skin .\non roentgenogram of right humerus there was an evidence of ill defined soft tissue swelling in the upper arm posteromedially with radiopacity in continuation with the surface of humerus suggestive of bony excrescences ( fig .\nmri right shoulder joint ( plain + contrast ) revealed a large 13 cm 5 cm 8 cm well defined , nonenhancing , lobulated , heterointense , predominantly fat intensity lesion with a small area of chondroid component measuring 2 cm 1.6 cm in posteromedial aspect of the proximal right humerus , seen completely separate from the adjacent muscles ( fig .\nvertical elliptical incision was taken over the posterior border of the right upper arm over the tumor .\nthe tumor was under the lower part of deltoid which formed the roof near the upper end of humerus , between the long and medial heads of triceps muscles ( fig .\n6 cm 5 cm 5 cm sized part of the tumor was under the long head of triceps displacing it medially along with radial nerve and vessels .\n7 cm 6 cm 3 cm sized part of tumor was under the medial head of triceps displacing it laterally .\nafter hemostasis , wound was closed with a suction drain in situ . the specimen ( fig .\n5a ) weighed 250 g. postoperatively a shoulder sling was given for 3 weeks to prevent any inadvertent fracture following the use of osteotome over the humerus during the surgery .\n1b ) of right humerus was normal and showed no bony excrescences . on gross pathology ,\nthe lesion was multilobulated , well circumscribed and irregular mass of size 12 cm 5 cm 8 cm with a bony part measuring 2.5 cm 2 cm 1 cm .\n5b ) , the lesion was composed of mature lipocytes that had an intimate relationship with the periosteum , consistent with parosteal lipoma .\nparosteal lipomas , benign adipose tissue tumors situated directly on bone cortex , are unusual neoplasms that appear to emerge from multidirectional mesenchymal modulation within the periosteum .\nperiosteal lipomas , chondrolipomas of soft tissue and lipomas of nerves but they are most commonly believed to originate from the periosteum .\nthese tumors are frequently associated with chondroid and/or osseous modulation , which permit subclassification into 4 distinct variants : ( i ) no ossification ; ( ii ) pedunculated exostosis ; ( iii ) sessile exostosis ; and ( iv ) patchy chondro - osseous modulation .\nparosteal lipoma presents as an immobile , nontender , slow growing mass over bones that is not fixed to skin .\non radiographs , a parosteal lipoma is a well - defined area of lucency located adjacent to a long bone . in one series of parosteal lipomas ,\n60% had definite bony alterations , mostly hyperostotic reactive changes ( fine linear densities , calcification , cortical thickening or undulation , or frank excrescences of bone ) , but these lipomas also have cortical bowing and smooth cortical erosions .\nparosteal lipomas have a homogeneous lobulated appearance and are adherent to the surface of the adjacent bone .\nwhen present , osseous excrescences may mimic osteochondromas , but the former lack the contiguity of the marrow space with the underlying bone that is characteristic of the latter .\nparosteal lipomas that gain clinical attention are those that compress neurovascular bundles and cause motor and sensory function deficits .\nthe tumor is identified on mr images as a juxtacortical mass with signal intensity identical to that of subcutaneous fat , regardless of pulse sequence .\nheterogeneity in these lesions is invariably present and corresponds to the pathologic components in the lesion .\nareas with intermediate signal intensity on t1-weighted images that are high signal intensity on t2-weighted images represent the cartilaginous components in parosteal lipoma .\nfibrovascular septa may cause a lobulated appearance of the fat component , with low - signal - intensity strands on t1-weighted images that become higher in signal intensity on the long tr images ( particularly with fat suppression ) .\nlarger areas of bone production surrounded by the lipomatous components are also well demonstrated with mr imaging .\nadjacent muscle atrophy , poorly demonstrated by ct , is identified on mr images as increased striations of fat in the affected muscle and is caused by associated nerve entrapment .\nthis finding is best appreciated on t2-weighted images because of the decreased signal intensity of normal muscle relative to fat .\nfinally , mr imaging best demonstrates the relationship of the tumor to the underlying native bone and muscle , and this information is important for surgical planning because parosteal lipoma is usually firmly adherent to the underlying cortex at the site of surface bone production .\npathologically the lesion is usually a multi - lobulated yellowish mass composed of mature adipocytes , and it is well encapsulated with a broad base of attachment to the underlying bone .\nmicroscopically , the fat cells of a parosteal lipoma appear histochemically identical to the adipocytes that are found in the subcutaneous tissues .\nthere has been no indication to date that this tumor undergoes malignant degeneration , although minimal cellular pleomorphism may occasionally occur .\nthe treatment of parosteal lipoma is complete surgical resection . in the case with nerve entrapment ,\nthe tumor must be removed before irreversible muscle atrophy occurs so as to maintain function .\nthe nerve must also be separated from the parosteal lipoma and care must be taken to spare it during surgical excision . in our case ,\nadequate surgical removal of a parosteal lipoma requires either subperiosteal dissection , which is the separation of the lesion from the underlying bone using an osteotome or segmental resection of bone ; this is in contrast to the relatively easy dissection for a soft tissue lipoma lying adjacent to bone .\nseveral cases have shown a malignant transformation having radiological and histological features of benign lipomas together with histologic fields of either malignant fibrous histiocytoma or liposarcoma .\nmalignant transformation of a lipoma should be suspected when rapid bone destruction is seen in a radiolucent lipoma .\nparosteal osteosarcomas and well - differentiated liposarcomas ( wdlps ) of soft tissue share several features : they are slowly progressive , locally aggressive tumors , tend to recur locally , and rarely or never metastasize if not dedifferentiated .\nmicroscopically , both are well differentiated tumors , very like their normal tissue counterpart . a biopsy is required from its two components , i.e. bony base and peripheral fat .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\ndr . rohan chaudhary performed the study design , data collections , data analysis , writing and he was the operating surgeon .", "answer": "introductionparosteal lipoma is an extremely rare benign tumor composed mainly of mature adipose tissue with a bony component.presentation of casethis study reports the case of a 65-year old woman with a big mass on the posteromedial aspect of the right upper arm since 1 year . \n the swelling was a slow growing , painless , nontender , immobile mass which was not fixed to skin . \n she had no complaints of painful or restricted movements of the shoulder joint . \n she had no history of trauma to the upper limb.mri revealed a large 13 cm 5 cm 8 cm well defined , nonenhancing , lobulated , heterointense , predominantly fat intensity lesion with a small area of chondroid component measuring 2 cm 1.6 cm in posteromedial aspect of proximal right humerus , seen completely separate from the adjacent muscles.discussionthe patient underwent surgery under general anesthesia . \n vertical elliptical incision was taken over the posterior border of the upper arm over the mass . \n the tumor was below the lower part of deltoid near the upper end of humerus , which formed the roof , and between the long and medial heads of triceps muscles . \n a part of tumor , measuring 6 cm 5 cm 5 cm , was under the long head of triceps displacing it along with radial nerve and vessels medially while the other part , measuring 7 cm 6 cm 3 cm , was under the medial head of triceps displacing it laterally . \n the tumor was excised undocking its periosteal attachment . \n the specimen weighed 250 g. on histopathology , the lesion was composed of mature lipocytes that had an intimate relationship with the periosteum . \n no cellular atypia or lipoblasts were seen.conclusionparosteal lipomas are rare neoplasias with no proven malignant potential . \n these tumors can be resected without much damage to the adjacent structures , thus preserving the function of the upper limb .", "id": 745} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is the most common endemic mycosis in the united states.1 it is most prevalent around the valleys of the mississippi and ohio rivers.2 in endemic areas , 50%80% of people have evidence of previous exposure to histoplasma.3 the fungus grows as a mold in the soil and when its microconidia are inhaled , causes infection and grows as a yeast in the host tissues .\nmost infected people remain asymptomatic or complain of a self - limiting flu - like illness .\nup to 25% of people infected with human immunodeficiency virus will develop disseminated histoplasmosis , with considerable morbidity and mortality.3 infection outside endemic areas and atypical presentations represent a diagnostic challenge .\nwe present a case of progressive disseminated histoplasmosis manifesting as a wasting syndrome with hypercalcemia , mimicking a metastatic cancer .\na 65-year - old , type 2 diabetic man presented with a 2-month history of constipation , polyuria , and unexplained weight loss of 54 lb .\nhe had lived in west pennsylvania until 13 years earlier , when he had moved to the texas panhandle area where he presented with the above complaints . on physical examination ,\nlaboratory test results revealed a hemoglobin of 10.6 ( normal range 1216 ) g / dl and a white blood cell count of 3.5 10 cells / l ( normal range 4.010.6 10 cells / l ) .\nbiochemistry tests showed a creatinine of 3.2 ( normal range 0.51.4 ) mg / dl , serum calcium of 12.4 ( normal range 8.410.3 ) mg / dl , and albumin of 3.5 ( normal range 3.75.1 ) g / dl .\nthe patient s parathyroid hormone level was low at 6 ( normal range 11.054.0 ) pg / ml and serum protein electrophoresis showed a normal pattern .\nbody computed tomography showed bilateral adrenal enlargement and a mass lesion at the base of the tongue ( figure 1 ) .\nmagnetic resonance imaging of the brain showed three left - sided brain lesions ( figure 2 ) .\nbiopsies of the tongue lesion and the left adrenal gland showed necrotizing granulomas containing budding yeast forms , consistent with histoplasmosis ( figures 35 ) .\nhistoplasmosis is rarely diagnosed in the texas panhandle area and we were unable to tell whether his presentation represented a reactivation of an old infection or progression of a newly acquired infection .\nafter adequate intravenous hydration , the patient s kidney function tests and serum calcium level reverted to normal .\nthe patient received a 4-week course of liposomal amphotericin b and was subsequently started on itraconazole .\ndissemination of h. capsulatum is common in the early stages of this fungal infection.1 symptomatic acute dissemination develops in immunocompromised patients.2 they present with a febrile illness that can be complicated by severe sepsis , acute respiratory distress syndrome , and disseminated intravascular coagulopathy . on the other hand , chronic progressive disseminated histoplasmosis\nis typically reported in middle - aged and elderly men who are not immunosuppressed.3 they present with a wasting syndrome , long - standing fever , and night sweats .\nthe infection may involve multiple organ systems , including the gastrointestinal tract ( with resulting ulceration ) , adrenal glands ( precipitating adrenal insufficiency ) , the reticuloendothelial system ( causing hepatosplenomegaly ) , bone marrow ( leading to pancytopenia ) , the central nervous system , and the lungs . on rare occasions ,\nprogressive disseminated histoplasmosis has been associated with hypercalcemia , and this is attributed to increased 1 , 25 dihydroxyvitamin d production from the fungal granulomas.410 a medline search ( january , 1946 to november , 2012 ) identified seven reported cases of disseminated histoplasmosis presenting with hypercalcemia .\nthe clinical presentation , risk factors that predisposed to histoplasmosis , and patient outcomes are reported ( table 1 ) . upon reviewing the cases and in comparison with the case at hand , the following features were noted . like our patient , most patients were middle - aged and elderly men with a limited degree of immunosuppression .\npresenting symptoms varied , with pulmonary complaints in two cases , gastrointestinal symptoms in two , wasting syndrome in three , including ours , and musculoskeletal complaints in another .\nhypercalcemia was symptomatic in some cases and an asymptomatic laboratory abnormality in others . in all cases ,\nthe diagnosis was difficult to make , and in three cases was established post mortem .\ntwo of the three patients who died , ie , the first and second cases , did not receive antifungal therapy , and treatment was delayed in the third patient who died , ie , the fourth case .\ndiagnosis of histoplasmosis relies on a multifaceted approach.11 histopathological examination , cultures , antigen and antibody detection , and molecular methods are commonly used in different combinations to establish the diagnosis .\na recent multicenter study evaluated the above - mentioned tests in the diagnosis of disseminated histoplasmosis and reported their corresponding sensitivities , ie , 74% for cultures , 76% for histopathology , 92% for antigen detection in urine and/or serum using a third - generation enzyme immunoassay , and 75% for antibody detection combining immunodiffusion and complement fixation assays.11 use of molecular methods in the diagnosis of histoplasmosis has been reported , but remains uncertain and is awaiting further study.12 the high sensitivity of antigen detection is plagued by significant cross - reactivity with other fungal antigens .\ncross - reaction occurs in 90% of patients with blastomycosis and in 60% of patients with coccidioidomycosis.13 testing both urine and serum yields better sensitivity .\nfurthermore , testing cerebrospinal fluid and bronchoalveolar lavage fluid might improve sensitivity in diagnosing central nervous system and pulmonary infections.14 it is worth mentioning that failure to detect histoplasma antigens does not rule out the diagnosis , and repeating the test in patients with progressive illness should be considered.3 severity of illness dictates antifungal treatment options and duration of therapy . for moderate to severe infection , liposomal amphotericin b for 12 weeks followed by a 12-month course of itraconazole is recommended.15 for milder cases , itraconazole for one year is indicated .\nfor histoplasmosis of the central nervous system , liposomal amphotericin b for 46 weeks followed by itraconazole for at least one year and until cerebrospinal fluid abnormalities and antigenemia or antigenuria resolve is recommended.15 antigen levels in serum or urine should be measured during therapy for progressive disseminated histoplasmosis and central nervous system infection , and for 12 months afterwards .\nten percent to 15% of patients experience a relapse.16 diagnosis and treatment in this group of patients follows the above outlined principles , but also includes long - term itraconazole maintenance therapy .\nour work has some limitations , not the least of which is the fact that it is a single case report .\nfurthermore , the diagnosis was based on a compatible clinical presentation and histopathological examination that could not be confirmed by culture , serology , or antigen detection .\nfurther research is needed to develop readily available tests , probably molecular diagnostic methods , with higher sensitivity and specificity to diagnosis histoplasmosis as well as other mycosis .\nacute disseminated infection presents with a sepsis syndrome , whereas chronic dissemination presents as a wasting syndrome .\nwe reported here a case of chronic disseminated histoplasmosis presenting with multiple mass lesions , weight loss , and hypercalcemia , mimicking metastatic cancer .\nin addition to malignancy , granulomatous disease , including fungal infection , should be considered in patients with similar presentation .", "answer": "histoplasmosis is a common endemic mycosis \n . the majority of infections involving this dimorphic fungus are asymptomatic . \n manifestations in symptomatic patients are diverse , ranging from flu - like illness to a more serious disseminated disease . \n we present here a case of chronic disseminated histoplasmosis mimicking a metastatic cancer . \n we reviewed the literature for cases of disseminated histoplasmosis presenting with hypercalcemia , focusing particularly on clinical presentation , risk factors predisposing for fungal infection , and outcome . \n we report a case of a 65-year - old diabetic male who presented with unexplained weight loss and hypercalcemia . \n multiple brain space - occupying lesions and bilateral adrenal enlargement were evident on imaging studies . \n biopsies showed caseating granulomas with budding yeast , consistent with histoplasmosis . \n the patient s symptoms resolved after liposomal amphotericin b and itraconazole therapy . \n granulomatous diseases , including fungal infections , should be considered alongside malignancies , in patients with similar presentation .", "id": 746} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndissemination and implantation of gastrointestinal malignancies throughout the peritoneal cavity result in peritoneal carcinomatosis ( pc ) , which is the second most frequent cause of death in colorectal cancer after metastatic disease to the liver . in 25% of colorectal cancer cases ,\nthe peritoneal cavity is the only site of metastatic disease . despite recent advances in the development of systemic chemotherapeutic agents , pc\nattempts have been made in the past decades to increase long - term survival in patients with pc by combining cytoreductive surgery ( crs ) to remove visible disease and hyperthermic intraperitoneal ( ip ) chemotherapy ( hipec ) to eradicate microscopic viable residual disease , with elevated and persistent drug concentration in the peritoneal cavity .\nthe peritoneal route of chemotherapy administration has the advantage of delivering the agent to the entire peritoneum after all adhesions have been lysed and before they have the opportunity to reform .\nthe peritoneal - plasma division concept allows a tenfold higher concentration of the chemotherapy to be reached in the abdominal cavity in direct contact with residual cancerous cells while minimal systemic absorption and adverse effects are expected .\nthe addition of hyperthermia results in a potentiation of cytotoxicity , improving its capability of penetration into tumoral masses and serving to rewarm the patient after a significant open procedure .\nthe ideal ip chemotherapeutic agent should be one that has maximal efficacy , offering optimal regional therapeutic benefits , while minimizing systemic toxicity .\nmitomycin c ( mmc ) has been the most frequently used ip chemotherapy for gastrointestinal malignancies . the high molecular weight of mmc limits its systemic absorption and toxicity after ip administration .\nmore recently , based on the efficacy of new systemic agents for patients with metastatic colorectal cancer , oxaliplatin and irinotecan have emerged as good options for peritoneal perfusion [ 6 , 7 ] .\nalthough there are no randomized trials comparing mmc with oxaliplatin as ip chemotherapy , a retrospective study with 539 patients with pc associated with colorectal cancer showed that both agents achieve similar median overall survival ( 32.7 vs. 31.4 months ; p = 0.925 ) .\nhowever , due to shortage of mmc in brazil , we have been using oxaliplatin as the preferred agent . despite all those potential benefits associated with crs with hipec , morbidity and mortality rates are substantial .\nlarge series of patients undergoing crs with hipec report mortality rates ranging from 1 to 8% [ 9 , 10 , 11 , 12 , 13 ] . in the only randomized study ( n = 105 ) comparing systemic chemotherapy ( fluorouracil - leucovorin ) with or without palliative surgery with aggressive crs with hipec , followed by the same systemic chemotherapy regime , the mortality rate in the crs with hipec group was 8% .\nin addition , surgical morbidity , such as postoperative ileus , anastomotic fistula , and wound infection , as well as medical morbidity , including pharmacological toxicity , cytopenia , bone marrow aplasia , renal toxicity , and hydroelectrolytic disorders , are quite frequent following crs with hipec [ 3 , 9 ] .\nthe most common reported complications include enteric fistula , intraabdominal abscess , pneumonia , small - bowel obstruction , pancreatitis , and neutropenia which often prolong the hospital stay . to the best of our knowledge ,\n, we describe the case of a previously healthy young man who underwent crs with hyperthermic ip oxaliplatin and developed one episode of tonic - clonic seizure on the second postoperative day .\na 26 year - old man presented in mid-2011 with increasing abdominal pain . in october 2011\nhe was found to have a poorly differentiated adenocarcinoma of the transverse colon with multiple peritoneal implants .\nit was consistent with a pt4 pn2 ( 4/28 ) pm1 colonic adenocarcinoma , kras wild - type . from january to july 2012\n, he received 12 cycles of folfiri ( folinic acid , 5-fluorouracil , and irinotecan ) plus bevacizumab at another institution and achieved complete clinical response . at that time\na pet - ct scan revealed lesions with increased fdg uptake in the peritoneum as well as in the colonic anastomosis . from june 2014 to june 2015 , he received 24 cycles of folfiri and cetuximab with initial response followed by stable disease . in september 2015 , he was first seen at our institution and , during a multidisciplinary meeting , it was decided to pursue crs with hipec ( oxaliplatin 300 mg / m ) , which was started on october 5 , 2015 . on the second postoperative day , the patient developed one episode of generalized tonic - clonic seizure which lasted for approximately 2 min .\nhe was started on phenytoin to prevent new episodes of seizures during the postoperative period .\non october 15 , due to no recurrence of seizures , the anticonvulsant was discontinued .\nhe stayed at the icu for only 72 h and had the first bowel movement 6 days after surgery . on the 7th postoperative day\n, he developed fever with no identified origin and was started on piperacillin - tazobactam and vancomycin . at this time , the patient was also complaining of left scrotal pain and swelling .\nan ultrasound of the testis was performed on october 17 and showed normal testicles and increased volume of the left epididymis with heterogeneous echogenicity .\nin addition , analysis of the epididymal waveform revealed a low - resistance pattern suggestive of acute epididymitis . despite all cultures having remained negative ,\nit was decided to switch antibiotics to amikacin for 10 days and to doxycycline for 14 days and treat the symptoms as infectious epididymitis .\nthe patient was discharged home on october 22 , 2015 , to complete antibiotics at the outpatient unit .\n. ten percent of adults experience a seizure some time during their life . each year , 300,000 people experience a first epileptic seizure ; most of them are younger than 18 years old .\nseizures result from a shift in the normal balance of excitation and inhibition within the central nervous system as well as from abnormal brain function .\nstudies indicate that 2530% of first seizures are acute symptomatic or provoked by a brain insult or a metabolic / toxic disturbance of brain function .\nprovoking factors include fever , head injury , excessive alcohol intake , withdrawal from alcohol or drugs , hypoglycemia , electrolyte disturbance , brain infection , ischemic stroke , intracranial hemorrhage , and proconvulsive drugs ( such as clozapine , maprotiline , tramadol , theophylline , and baclofen ) .\nthere are several alterations in the physiology of patients during crs and the administration of hipec .\nthe body temperature increases significantly due to hipec , they experience transient hyperglycemia secondary both to stress from surgery and hyperthermia , as well as the presence of dextrose in the perfusate .\nhowever , none of those abnormalities has ever been reported to cause seizures , as seen in our case .\nthere are no published articles regarding neurological complications such as seizures in patients who were submitted to hipec with oxaliplatin .\nthere is , however , one case report of a 37-year - old female patient with a previous history of seizure disorder who underwent crs and hipec with mmc without intraoperative complications and developed signs and symptoms of cerebral edema 4 h after the operation was completed .\nshe eventually died of cerebral edema , with no established etiology . despite a normal eeg , it was hypothesized that crs with hipec could have caused unrecognized partial complex seizures leading to acute cerebral edema .\neven though our patient had no history of seizure disorder , it is a possibility that the seizure threshold may have been lowered secondary to the stress of surgery and hyperthermia .\nin fact , seizures are a rare side effect of intravenous oxaliplatin , which are usually associated with posterior reversible leukoencephalopathy syndrome ( pres ) .\npres is characterized by neurologic symptoms such as headache , altered mental status , visual disturbances , and seizures with typical lesions on neuroimaging shown as bilateral , subcortical , symmetric , and vasogenic edema . however , our patient had no symptoms or radiologic findings of pres .\nthere is a published case of a previously healthy man with mixed adenoneuroendocrine carcinoma who had seizures after the third and fourth cycles of intravenous folinic acid , 5-fluorouracil , and oxaliplatin ( folfox ) with no signs of pres .\nafter the chemotherapy regimen was switched to folfiri , he never had another event . in this case , the authors attributed the seizures to the intravenous oxaliplatin .\nour patient had no electrolyte abnormalities , no signs of infection , brain structural alteration , or other metabolic disorder that could possibly explain the single episode of seizure .\ntherefore , it may be possible that the seizure was caused either by the physiological modifications that occurred during hipec or by ip oxaliplatin .\nbecause of the increasing use of crs with hipec as an option to treat selected patients with pc , it is important to report those postoperative complications .\nthis article reports an unprecedented case of seizure in a previously healthy patient who underwent crs with ip oxaliplatin due to metastatic colon adenocarcinoma . despite this being a rare case ,\nthe corresponding author acknowledges that she is responsible for complying with ethical requirements and declares that the patient was correctly informed , and written informed consent was obtained ; the confidentiality of the patient was strictly preserved .\nthe patient was informed about the submission of the manuscript and will be acquainted when the article is published .", "answer": "cytoreductive surgery ( crs ) with hyperthermic intraperitoneal ( ip ) chemotherapy ( hipec ) is believed to improve outcomes in well - selected patients with peritoneal carcinomatosis . however , morbidity and mortality rates associated with this procedure are substantial . here \n , we describe the case of a previously healthy young man who underwent crs with hyperthermic ip oxaliplatin and developed one episode of tonic - clonic seizure on the second postoperative day .", "id": 747} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin bacteria , the number of characterized small , noncoding rnas ( srnas ) that have intrinsic functions as regulators has steadily increased in recent years .\nmany srnas act by posttranscriptionally regulating mrnas via basepairing interactions ( 1 ) . in escherichia\ncoli , all of the srnas that act by basepairing affect either the stability or translation of the mrna target . in most cases ,\nthe mrna targets of srna regulation are trans - encoded , and the srna : mrna basepairing interactions are interrupted by gaps in the pairing .\nfurther , most srnas in this class bind to the rna chaperone hfq , which has been shown to facilitate the interaction between many srnas and their targets ( 2 ) . here\n, we describe a program , targetrna , which can effectively predict mrna targets of basepairing srnas .\nwhile a number of approaches have been described for identifying targets of microrna genes in eukaryotes ( 37 ) , there have been relatively few computational tools developed for characterizing targets of srna regulators in bacteria .\n( 8) describe one such tool , which has been applied successfully in the genome of listeria monocytogenes , though the program is not available as a webserver .\nvogel and wagner ( 9 ) offer a comprehensive review of approaches , both computational and experimental , for identifying targets of bacterial srnas .\nthe program we describe here , targetrna , is accessible via a webserver that has been operating and publicly available since 2005 , processing approximately 1000 sequence submissions per month .\nthe webserver consists of a 16 cpu parallel computing cluster , and targetrnas underlying search algorithm has been designed for parallel computation , in order to increase performance and to process efficiently a large number of sequence submissions .\nthe predictive performance of targetrna has been validated experimentally in e. coli using both northern blot and microarray experiments ( 10 ) .\nadditionally , predictions from targetrna have been validated in other organisms , such as in vibrio cholerae ( 11 ) and in neisseria meningitidis ( 12 ) , or are consistent with experimentally validated interactions , such as in salmonella ( 13 ) .\ntargetrna takes , as input , a genomic sequence that may correspond to a srna gene .\ntargetrna then searches each annotated message in the user - specified genome for mrnas that evince statistically significant basepair - binding potential to the input srna sequence .\nbasepair - binding potential of a srna with each mrna is determined using one of two user - selected hybridization scoring methods .\na detailed description of the hybridization scoring methods has been described previously ( 10 ) . in summary ,\n waterman dynamic program ( 14 ) , except that instead of assessing homology potential , basepairing potential is assessed .\nthe stacked basepair model of hybridization scoring is based on stacking and destabilizing energies of interacting sequences .\nthe stacked basepair model calculates the minimum free energy of hybridization for two rna sequences , without allowing intramolecular basepairings .\nthis model for hybridization scoring closely follows that developed and used for the rnahybrid algorithm ( 7 ) .\nthe stacked basepair model is computationally more intensive than the individual basepair model and , as a result , increases the time required for calculating basepair binding potential by a factor of approximately five for most sequence inputs .\nonce targetrna determines hybridization scores for the srna sequence with each message in a genome , the statistical significance of each potential srna : mrna interaction is assessed .\ndetermination of statistical significance is similar to that described for the rnahybrid algorithm ( 7 ) .\nten thousand random rna sequences are generated such that the nucleotides in the random sequences are drawn from the distribution of nucleotides in the actual mrna search space .\nthe hybridization score is computed for each of these random sequences and the srna sequence .\nthe resulting distribution of ten thousand hybridization scores is used to estimate a p - value for an srna : mrna hybridization score by determining the probability of observing a score , by chance , equal to or less than the given srna : mrna hybridization score . after computing the statistical significance of basepair binding between a srna sequence and each message in a genome , targetrna outputs a ranked list of mrnas in a genome\nwhose basepair - binding potential with the srna sequence meets a significance threshold ( the default is a p - value 0.01 ) .\nmessages with statistically significant basepair - binding potential are considered candidate targets of srna regulation .\nfigure 1 illustrates example output from targetrna when searching for mrna targets of the srna gene spot42 in e. coli ( 15 ) . as shown in figure 1 , targetrna outputs , for each candidate mrna target identified , an annotation of the mrna , a visual representation of its predicted basepair binding with the srna , and a p - value corresponding to the significance of the hybridization score of the predicted srna : mrna interaction . to facilitate further investigation of candidate message targets , each identified target\nis linked to the entrez gene database ( 16 ) from the national center for biotechnology information .\nthe time required for targetrna to process an input sequence and generate results depends on the length of the sequence and the parameter selection but typically takes only a few seconds .\noutput from targetrna is available via both a formatted web page and a text file . \n\nfigure 1.the figure illustrates example output from using the targetrna webserver with default parameter settings to search for message targets of the srna spot42 in escherichia coli . in the middle of the figure , the six message targets predicted by targetrna are summarized . in the bottom of the figure ,\nthe predicted interaction between spot42 and one of the six predicted targets , galk , is illustrated .\nthe predicted interaction between spot42 and galk consists of 41 nucleotides ( from nucleotide 21 to 61 ) in the 109 nucleotide srna spot42 , and 39 nucleotides ( from 19 nucleotides upstream of the galk start codon to 20 nucleotides downstream in the galk coding sequence ) in the galk message .\nthe figure illustrates example output from using the targetrna webserver with default parameter settings to search for message targets of the srna spot42 in escherichia coli . in the middle of the figure ,\nthe six message targets predicted by targetrna are summarized . in the bottom of the figure ,\nthe predicted interaction between spot42 and one of the six predicted targets , galk , is illustrated .\nthe predicted interaction between spot42 and galk consists of 41 nucleotides ( from nucleotide 21 to 61 ) in the 109 nucleotide srna spot42 , and 39 nucleotides ( from 19 nucleotides upstream of the galk start codon to 20 nucleotides downstream in the galk coding sequence ) in the galk message .\nthe targetrna webserver provides a number of advanced search options that allow users more flexible control over the target search space beyond that provided by the default parameter settings .\ntargetrna provides the option of automatically identifying and removing the region of the srna sequence corresponding to the terminator stem - loop since , in many cases , the terminator stem - loop does not participate in the srna : mrna interaction .\nusers have the option of focusing their search around the 5 utr or 3 utr of messages , specifying the number of nucleotides to include upstream and downstream of the messages start codon or stop codon .\nspecifying regions around the 5 utr to be searched may be advantageous since many documented target interactions occur in particular regions , such as around the ribosome - binding sites , of messages .\na seed , which corresponds to a minimum required length for at least one stretch of consecutive basepaired nucleotides in the srna : mrna interaction , can also be specified .\nthe seed is meant to reflect , biologically , the initial interaction between srna and mrna , which has been shown in some cases to be a stretch of unpaired nucleotides in a loop of the srna that first basepairs with the target message . while targetrna searches each annotated message in a genome by default , users have the option of searching an individual message in order to explore more carefully a particular interaction predicted by targetrna .\nwhen searching for targets of a srna in a given organism , targetrna also offers the option of calculating the hybridization scores of orthologous targets with orthologous srnas in other organisms .\nsince many srna genes are conserved across related species , the program can thus suggest whether it is likely that the targets and hybridization interactions are conserved .\nthe various user - adjustable program parameters have the benefit of allowing a user to explore the tradeoff between sensitivity and specificity when assessing results of the targetrna program .\nfor instance , removing the srna terminator sequence , focusing searches for targets to regions around translation start sites of messages , and setting a seed threshold above about five nucleotides can eliminate many false positive predictions .\nhowever , too much stringency with these parameters may result in a lack of identification of true targets .\nfor example , some srna : mrna interactions include the terminator sequence of the srna , such as the oxys : fhla interaction ( 17,18 ) in e. coli , and some srnas interact with messages somewhat distant from the message 's start of translation , such as dsra ( 19 ) and rpra ( 20 ) when interacting with rpos in e. coli .\nthus , the default parameter settings provide only a starting point for message target investigation .\ndefault parameter settings were determined by optimizing performance of targetrna on srna : mrna interactions in e. coli reported prior to 2005 .\nconsidering the recent growth in the number of srna : mrna interactions reported in the literature across a range of bacterial species , we have revisited the issue of whether different default parameter settings would improve the performance of targetrna .\nwhen accounting for a broad set of srna : mrna interactions in different species , we did not find a set of parameters that led to significant improvement , over the current default parameter settings , in successfully identifying targets of srna regulation .\na recent addition to the targetrna webserver is a companion program to targetrna called rnatarget , which provides reverse searching capabilities . whereas targetrna takes as input the sequence of a candidate srna region and searches the genome for possible message targets , rnatarget takes as input the sequence of a candidate message target of an unknown srna regulator and searches the genome for regions containing possible srna regulators of the target sequence .\nrnatarget searches all intergenic sequences greater than 50 nucleotides in length in the genome for regions that evince significant basepair - binding potential to the input candidate target sequence .\nrnatarget outputs a ranked list of intergenic regions in the genome whose basepair - binding potential with the target sequence meets a significance threshold ( the default is a p - value 0.01 ) .\nintergenic regions with statistically significant basepair - binding potential are considered as candidate regions corresponding to a srna regulator .\nfigure 2 illustrates example output from rnatarget when searching intergenic regions for candidate srna regulators of the mrna target galk in e. coli .\nit has been reported previously that the srna spot42 , which resides in the intergenic region of the genome between genes pola and yiha , interacts with and regulates galk ( 21 ) . as shown in figure 2 , rnatarget outputs , for each intergenic region identified , the flanking protein - coding genes , a visual representation of the predicted basepair binding between the two genomic sequences , and a p - value corresponding to the significance of the hybridization score of the predicted mrna : srna interaction .\nit is worth noting that rnatarget searches only for genomic regions demonstrating basepair - binding potential to the target sequence , it does not attempt to identify other properties of genomic sequences suggestive of srna genes , such as transcription initiation or termination sequences .\nseveral other computational programs are available for predicting srna genes in a genome based on various sources of evidence , including transcription signals and comparative genomics information ( 22 ) . \n\nfigure 2.the figure illustrates example output from using the rnatarget program with default parameter settings to search for intergenic regions in e. coli that evince basepair binding potential with a region of the galk message around its ribosome binding site .\n( b ) details of the predicted interaction between galk and one of the intergenic regions , between genes pola and yiha , is shown .\nthe srna spot42 , which resides in this intergenic region , is known to interact with and regulate galk ( 21 ) .\nthe predicted interaction between the intergenic region and galk consists of 41 nucleotides ( from nucleotide 167 to 207 ) in the 380 nucleotide pola \nyiha intergenic region , and 39 nucleotides ( from 19 nucleotides upstream of the galk start codon to 20 nucleotides downstream in the galk coding sequence ) in the galk message .\nthe figure illustrates example output from using the rnatarget program with default parameter settings to search for intergenic regions in e. coli that evince basepair binding potential with a region of the galk message around its ribosome binding site .\n( b ) details of the predicted interaction between galk and one of the intergenic regions , between genes pola and yiha , is shown .\nthe srna spot42 , which resides in this intergenic region , is known to interact with and regulate galk ( 21 ) .\nthe predicted interaction between the intergenic region and galk consists of 41 nucleotides ( from nucleotide 167 to 207 ) in the 380 nucleotide pola \nyiha intergenic region , and 39 nucleotides ( from 19 nucleotides upstream of the galk start codon to 20 nucleotides downstream in the galk coding sequence ) in the galk message .\ntargetrna is a freely available webserver that predicts message targets of srna action in bacteria .\nassessment of targetrna 's performance suggests that the predictive performance of targetrna varies between srnas .\nfor some srna regulators where one or more targets have been reported in the literature , targetrna successfully identifies the majority of targets , whereas for other srna regulators with one or more targets , targetrna identifies few , if any , targets ( 10 ) .\ntargetrna operates under the assumption that the basepair - binding potential of two genomic sequences , corresponding to an srna and a mrna target , can serve as a predictor , albeit imperfect , for the interaction of the two rnas .\nconserved basepair - binding potential of two genomic sequences across different genomes can provide further evidence for srna : mrna interaction .\nhowever , other factors that may contribute to srna : mrna interactions , such as rna secondary structure or the role of hfq , are not modeled by the program . as more examples of srna : mrna interactions are reported across a range of bacteria , we will gain a better understanding of the various rna properties and components within the cell that contribute to the interactions , and computational methods that aid in investigation of these interactions can be evolved appropriately to incorporate the new insights .", "answer": "many small rna ( srna ) genes in bacteria act as posttranscriptional regulators of target messenger rnas . here \n , we present targetrna , a web tool for predicting mrna targets of srna action in bacteria . \n targetrna takes as input a genomic sequence that may correspond to an srna gene . \n targetrna then uses a dynamic programming algorithm to search each annotated message in a specified genome for mrnas that evince basepair - binding potential to the input srna sequence . \n based on the calculated basepair - binding potential of each message with the given srna regulator , targetrna outputs a ranked list of candidate mrna targets along with the predicted basepairing interaction of each target to the srna . \n the predictive performance of targetrna has been validated experimentally in several bacterial organisms . \n targetrna is freely available at http://snowwhite.wellesley.edu/targetrna .", "id": 748} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprogressive neurologic deterioration or back and leg pain in children with a history of myelomeningocele ( mmc ) surgery may be due to cord tethering or growth of an intradural inclusion tumor .\nloss of motor function in the lower extremities , gait abnormality , back or leg pain , scoliosis , and foot deformity are common findings in postsurgical tethering .\nhere , we report a child who developed progressive neurological deterioration and severe back and leg pain subsequent to large infected dermoid tumor extending underneath the skin to the spinal canal and intramedullary area .\na 3-year - old boy was referred to neurosurgical department because of severe back and leg pain and motor regression .\nhe was a known case of lumbar mmc and was operated at 8 months of age .\nhe could sit at 11 months of age and stand at age of 2 years on his knees , but could not move the distal part of his legs at all .\nhis back pain had started 3 months ago , which was severe at night and made him unable to sit .\nsubsequently , he experienced severe leg pain , which prevented him from moving the proximal part of his lower extremities and his mother faced difficulty while cleaning him after urination or defecation . on physical examination , the child was afebrile , but very irritable , with good mental performance , and normal neurological examination of upper limbs .\nboth lower extremities had lost any movement in proximal and distal parts ( 0/5 ) .\na small tender bulging was identified in his back under the mmc repair incision for one week before admission , but no dermal sinus was found inside or around the incision . spinal magnetic resonance imaging ( mri )\nwas performed one month before surgery , which revealed cord tethering ( cord at l4- l5level ) .\ndistal cord was attached to a mass , which was isointense in t1- and hypointense in t2-weighted images .\nit was extending from distal cord through the bony defect to the extraspinal canal space .\nthe cord was dilated from the level of tethering to l1level with a lesion , which was isointense to hypointense in t1- and hyperintense in t2-weighted images , dissimilar to the intensity of cerebrospinal fluid [ figures 1 and 2 ] .\nnotice the hypointense signal inside the expanded cord compatible with infected dermoid tumor found during surgery hypointense mass in t2-weighted image is extending from distal cord through the bone defect to the extraspinal canal space and the prior mmc surgery field the child underwent surgery with the suspicion of tethered cord associated with an inclusion tumor .\nin the prone position , the prior midline vertical incision was opened . during the dissection of subcutaneous tissue ,\ndura mater , cord and dermoid tumor were attached to each other at the depth of previous surgical field , and the tumor was extending from the extraspinal area to the intramedullary space between l4 and l1 vertebral levels .\nmicrosurgical release of all intradural adhesions was performed to achieve circumferential untethering of spinal cord associated with gross total resection of intramedullary mass .\ncomplete excision of the dermoid cyst and capsule were performed , which was followed by primary closure of the dura .\non histopathological examination , specimen had the characteristic features of a dermoid cyst , with simple squamous epithelium , hair follicles , and cholesterol - containing debris .\nhe could move proximal part of his lower extremities with score of 1 - 2/5 , but was unable to stand on his knee as he could do before .\nchildren with mmc are born with a wide range of neurological deficits that will remain after primary repair of lesion .\nany new changes in the previous neurological , urological or orthopedics status warrant an extensive investigation to rule out the possible causes , especially tethered cord syndrome .\ntethered cord is a common complication following mmc surgery , which may be found in most patients when they are evaluated with spinal mri , but symptomatic tethering occurs only in 10 - 30% of them .\ntethered cord may present with subtle changes in prior neurophysical situation , which become progressive and disabling if neglected .\nspinal cord tethering due to dermoid cyst subsequent to mmc surgery has been reported so far , which can occur decades after closure.[58 ] all patients with symptomatic tethered cord have attachment of spinal cord to the prior closure site , which can be associated with inclusion tumors in 16% of instances .\ndermoid tumors following mmc surgery may result from inadequate excision of dermal elements during dissection of placode or dura mater from the skin or with implantation of dermal elements inside the repair site .\n, this tumor can be an associated abnormality with mmc , which was undiagnosed or neglected because of very small size at the time of primary repair , especially during surgery without magnification .\ncases of dermoid tumor in mmc children who were operated during the intrauterine period have been reported , suggesting a higher potential for rapid growth of this tumor in lesions that were closed in utero rather than after birth .\ndermal sinus tract as a rare congenital abnormality is accompanied by inclusion tumors in 43% of instances , wherein most tumors are dermoids .\nintramedullary spinal abscess without sinus tract is extremely rare , but a devastating condition in children.[1216 ] intramedullary abscess and dermoid tumor without dermal sinus have been reported before ; however , not following mmc repair and especially not associated with tethered cord . in order to explain infected dermoid tumor in this patient with prior mmc repair , we propose several explanations\nimplantation of bacteria during closure of mmc sac can lead to abscess formation but occurence three years after the first surgery seems to be unusual .\nmicroscopic sinus tract through the preceding mmc surgery incision can be a way for bacteria to reach the subcutaneous space .\nhematogenous superinfection of the dermoid cyst during repeated urinary tract infections in mmc patient is another possiblity for abscess formation in this case .\ndermoid tumors , even infrequent , should be considered in the differential diagnosis of the causes of neurological deterioration in patients with a history of mmc repair . along with tethered cord syndrome\n, dermoid tumor can complicate the prior neurological and physical status of the child , and should be searched vigilantly during evaluation of these patients . because of rapid growth of dermoid tumors and associated infection , these can deteriorate the previous neurological status in a more aggressive and destructive manner as compared to tethered cord per se .\nawareness of such pathology in patients with previous history of myelomeningocele repair , early diagnosis and surgical intervention can provide better result with less disability .\ntethered cord syndrome should be investigated in any patient with a history of mmc repair if one finds neurological , orthopedics , or urological deterioration .\ndermoid tumor is considered as an important differential diagnosis during thorough evaluation of the causes of worsening . in order to minimize the risk of dermoid tumor development following mmc surgery , any residual epidermal or dermal elements\nthe operative field should be explored accurately proximal and distal to the sac to find any associated anomaly or minute inclusion tumor and prevent late inclusion tumor formation and tethered cord .", "answer": "intramedulary dermoid tumors are rare tumors mostly found associated with dermal sinus tracts . \n spinal dermoid tumor can occur after myelomeningocele repair . \n infected dermoid tumors are reported in patients with dermal sinus tracts as well , but have never been reported subsequent to myelomeningocele surgery . here , \n we report a rare association of infected dermoid tumor with tethered cord without dermal sinus tract in a child who had been operated for myelomeningocele during infancy .", "id": 749} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnearest neighbor approaches were developed to predict the folding stabilities of nucleic acid secondary structures ( 1 ) .\nthese parameter sets utilize empirical rules , generally derived from optical melting experimental data , as the basis of the predictions . for rna , rules exist for predicting both free energy and enthalpy change of watson crick helices , gu pairs and loops ( 25 ) . parameters for dna have also been assembled for predicting watson \ncrick pair free energy and enthalpy change and free energy changes of loops ( 6,7 ) .\nthese parameter sets are the basis of computer programs that predict low free energy secondary structures .\nsuch programs include mfold / unafold ( 8,9 ) , the vienna rna package ( 10 ) , rna structure ( 2 ) , rnasoft ( 11 ) and sfold ( 12 ) .\nadditional approaches that use statistical learning of parameters for rna folding have also used the rules from the nearest neighbor methods and derived new parameter values ( 13,14 ) .\nnearest neighbor parameter sets include both a set of rules , called either equations or features , for predicting stability and a set of parameter values used by the equations ( 14 ) . for rna ,\nseparate rules exist for predicting stabilities of helices , hairpin loops , small internal loops , large internal loops , bulge loops , multibranch loops , exterior loops and pseudoknots .\ngiven the number of rules and constraints on the length of journal publications , it is difficult to assemble all the parameters in one publication and provide meaningful tutorials for using the parameters .\nthis is a barrier to software development for novel algorithms that could take advantage of the parameters .\nfor example , many software packages that use rna parameters still implement the set of parameters assembled in 1999 ( 4 ) , in spite of the fact the rna parameters were updated in 2004 ( 2 ) based on experimental results .\nthe nearest neighbor database ( nndb ) is a web - based tool for assembling and archiving complete nearest neighbor sets , including rules and values .\ncurrently , the 1999 and 2004 sets of rna folding parameters are provided ( 25 ) .\nthe nndb is built using a set of static html , specifically xhtml 1.0 transitional pages with a page hierarchy shown in figure 1 .\ntext is encoded in unicode ( utf-8 ) to facilitate display of equations in pages with diverse browsers running on diverse operating systems .\nthe top - level page provides access to a help page , available parameter sets and a page of references to rna optical melting experiments .\nadditionally , links provide downloading of the whole database in either zip or gzipped tar format .\nthe help page introduces the purpose of the database and defines basic terms , including the set of structural features defined by secondary structures .\nfor example , figure 2 , from the help page , shows an rna secondary structure that illustrates the loop features covered by nearest neighbor parameter sets .\nthe basic equations for utilizing the parameters to extrapolate folding free energy changes to temperatures other than 37c and to predict melting temperatures are also provided . \n\nthis figure illustrates the page hierarchy by following the linked pages down through the 1999 parameters and down to the hairpin loop pages .\nnote that there are five example calculations for hairpin loops to illustrate the separate sequence - dependent rules that are used depending on the specific loop . \n\nfigure 2.an rna secondary structure illustrating the types of features included in nearest neighbor parameter sets .\ninternal loops have nucleotides not in canonical pairs on each of two strands , but bulge loops have nucleotides not in canonical pairs on only one strand .\nformally , a pseudoknot occurs when there are at least two pairs , with indices i paired to j and i paired to j , that satisfy the condition i < i < j < j. the pseudoknot helix is often considered to be composed of the fewest pairs that need to be removed to relieve the pseudoknot ( 19 ) . in this structure ,\nthis figure illustrates the page hierarchy by following the linked pages down through the 1999 parameters and down to the hairpin loop pages .\nnote that there are five example calculations for hairpin loops to illustrate the separate sequence - dependent rules that are used depending on the specific loop .\nan rna secondary structure illustrating the types of features included in nearest neighbor parameter sets .\ninternal loops have nucleotides not in canonical pairs on each of two strands , but bulge loops have nucleotides not in canonical pairs on only one strand .\nformally , a pseudoknot occurs when there are at least two pairs , with indices i paired to j and i paired to j , that satisfy the condition i < i < j < j. the pseudoknot helix is often considered to be composed of the fewest pairs that need to be removed to relieve the pseudoknot ( 19 ) . in this structure ,\nthe tan nucleotides are in pairs that could be removed to relieve the pseudoknot . for each set of parameters ,\nfor example , the 1999 rna rules predict only folding free energy changes ( 4 ) , but the 2004 rules can be used to predict both folding free energy and enthalpy changes ( 2,5 ) . for each structural feature\n, a page defines the basic equations and provides links to parameter values ( in plain text and html ) , references and tutorial pages ( e.g. figure 3 ) .\nthe number of tutorials varies from feature to feature ; the set of tutorials is designed to cover each type of rule that can be encountered in practice .\n crick helix parameters are covered with two tutorials , one for self - complementary and one for non - self - complementary strands .\nthese two tutorials also demonstrate the difference in the calculation when there are terminal au base pairs , which receive a free energy and enthalpy change penalty ( 3 ) , because the self - complementary duplex example has two terminal au pairs and the non - self - complementary case has no terminal au pairs . \n\nthis tutorial demonstrates the prediction of folding free energy change for a hairpin loop of six unpaired nucleotides using the 2004 parameters ( 2,3 ) . an example tutorial from the database .\nthis tutorial demonstrates the prediction of folding free energy change for a hairpin loop of six unpaired nucleotides using the 2004 parameters ( 2,3 ) .\nindividual pages above the level of value tables have top banner , a left navigation bar that allows the user to navigate back up the hierarchy to any level above and a bottom bar with the date of last editing . for pages edited after the database has gone online , previous versions of the page are available using this bottom content bar . to facilitate indexing by search engines ,\nall pages have a descriptive title , including the set of parameters to which it belongs ( if applicable ) .\nthe first release of the nndb contains the rna folding rules assembled in 1999 and 2004 ( 25 ) .\nthese rules represent the most recent set of parameters and a prior set that is widely used in software packages . because folding rules are derived to work as a set , the two versions of rules and values should not be mixed and the website hierarchy reinforces this .\nit is anticipated , for example , that additional pages will be written to include nearest neighbors for dna folding ( 6,7 ) and for predicting rna pseudoknot stabilities ( 1518 ) .\nadditionally , the values derived from the re - estimation of the values of the 1999 parameter set using the set of known rna secondary structures will also be included ( 14 ) .\nthe nndb is designed to provide a convenient location for assembling parameter sets for predicting the stability of nucleic acid secondary structures .\nit is modular in design , which facilitates its future expansion to contain additional parameter sets .\nfurthermore , the web format makes it feasible to provide extensive tutorials for utilizing the parameters , which is generally not possible in print .\nthe creation of the nndb was supported by united states national institutes of health grants gm076485 to d.h.m . and gm22939 to d.h.t . funding for open access charge : united states national institutes of health .", "answer": "the nearest neighbor database ( nndb , http://rna.urmc.rochester.edu/nndb ) is a web - based resource for disseminating parameter sets for predicting nucleic acid secondary structure stabilities . for each set of parameters , \n the database includes the set of rules with descriptive text , sequence - dependent parameters in plain text and html , literature references to experiments and usage tutorials . \n the initial release covers parameters for predicting rna folding free energy and enthalpy changes .", "id": 750} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nradiological investigations and therapeutics have become an integral part of the management of critically ill patients in the intensive care unit ( icu ) .\npatients admitted to the icu routinely undergo bedside imaging procedures such as chest radiographs for diagnosing heart , lung and other pathology , and for confirmation of the position of devices like endotracheal tubes , nasogastric tubes , central venous catheters and intercostal drains .\na review article has suggested that among icu patients , up to 65% of daily chest radiographs and 70 - 75% of chest computerized tomography ( ct ) scans reveal significant or unsuspected abnormalities that may lead to a change in the patient 's management .\nfurther , critically ill patients are frequently transported to the ct scan as well as digital subtraction angiography suites for diagnostic and therapeutic procedures such as angiography , embolization and stenting . in most situations ,\nthe icu team is responsible for the transport and management of the patient in the radiology department for these procedures .\nthere is , therefore , potential radiation exposure to healthcare workers , particularly for those working for long periods of time in the icu .\nepidemiological data indicates that the exposure to even low - dose radiation may be a cause for concern because such exposure can result in leukemia , thyroid malignancies and other cancers .\nnonneoplastic effects of radiation include genetic mutation and developmental malformation in children whose mothers were exposed to radiation during pregnancy .\na number of studies have looked at radiation exposure in critically ill patients undergoing repeated radiological procedures .\none study has specifically focused on the pediatric age group probably in view of the high ratio of exposure to patient size and the potential for long - term sequelae as the radiation effects have a longer period to become manifest . however , the available literature on the extent of radiation exposure to icu personnel is scarce and relates mainly to the level of scattered radiation within the icu .\nthe conclusion of these studies is that the level of radiation exposure is extremely low and does not pose a hazard to icu personnel .\nnone of these studies have considered the additional radiation exposure to icu personnel involved in the management of critically ill patients in the radiology department . in our icu in a tertiary care cancer referral center , resident doctors working on 12 h shifts in the icu are also responsible for the transport and management of icu patients when they undergo diagnostic and therapeutic procedures in the radiology department .\nwe , therefore , carried out this study to determine the total radiation exposure to icu resident doctors involved in the course of their duties .\nwe conducted a prospective , observational study in the icu and postanesthesia care unit ( pacu ) of a 500-bedded tertiary care cancer referral center in mumbai , india from september 2012 to february 2013 .\nall resident doctors who gave voluntary written consent to participate in the study were included .\nsince the study did not involve patient contact , the requirement for obtaining consent from patients was waived by the ethics committee .\nthe study was carried out in accordance with the principles of good clinical research practice .\nthe resident doctors provide 24 h cover , working in 12 h shifts , with four doctors in each shift . in each shift\nthe icu has a total of 14 beds as shown in figure 1 . on another floor\nis the pacu with 23 beds , subdivided into 14 postoperative recovery room beds and 9 intensive care beds [ figure 2 ] .\nresidents provide care for patients in the icu and pacu and also accompany patients from these locations for radiological procedures in the ct scan or interventional radiology suites .\nlocation of thermoluminescent dosimeters are shown with filled triangles layout of postanesthesia care unit showing location of thermoluminescent dosimeter in pacu ( tld surrounded by beds ) and other in long lobby as control tld to detect levels of radiation , we used thermoluminescent dosimeters ( tlds ) which are a type of radiation detector .\nthe tld measures cumulative dose of ionizing radiation exposure by measuring the amount of visible light emitted from a crystal in the detector when the crystal is heated .\ntlds can measure a wide dosimetric range ( from 10 gray to 10 grays ) of radiation exposure and are routinely used as personal dosimeters because they are small in size , convenient to use and not expensive .\na tld was given to each of the four resident doctors ; they were handed over to the next team during shift changeover .\nin addition , three tlds were kept in nursing stations in icu , and one tld was placed in the pacu .\none tld was kept in the doctors ' duty room which was within the premises of the icu , and the last was kept as a control in the office of the department of anesthesia , critical care and pain , remote from icu and pacu , and where no radiological procedures were performed .\nthe layout of icu and pacu is represented by figures 1 and 2 respectively and locations of tlds are marked with filled triangles .\nthe participating resident doctors were instructed to wear the tlds at all times during their duty hours .\nstaff not required to be present during radiographic procedures were kept at least 3 m away from the patient ( a distance at which exposure from scattered radiation is considered negligible ) .\nit was ensured that patients who were shifted from icu to the radiology suite were accompanied by one icu resident and that the resident was wearing his tld throughout .\nresidents , if required to be directly involved in the radiologic procedure in suites , wore lead aprons , and the tld was underneath the lead apron . bedside chest\nx - rays in the icu were done by siemens multimobil 2.5 ( manufactured by siemens ltd , goa , india ) , ct and ct guided biopsies were performed on siemens somatom emotion 16 ( manufactured by siemens shanghai medical equipments ltd , shanghai china ) and ge light speed 16 ( manufactured by general electric co. , milwaukee , usa ) respectively .\ninterventional radiology procedures were carried out using ge innova 4100 iq ( manufactured by ge medical systems , france ) .\nthe study was carried out in two phases of 3 months each . at the end of the first phase ,\nthe tlds were handed over to department of nuclear medicine for analysis and another set of tlds was issued at the same time . during the period of the study , we maintained a database of procedures performed both in the icu and in the radiological suites along with the bed number and the patient 's hospital registration number .\nthe primary outcome of this study was to quantify the cumulative radiation exposure to the resident doctors working in the icu over a period of 6 months in the course of their duties .\nthe secondary outcomes were to measure the cumulative scattered radiation exposure in various areas of the icu calculated as the average of readings of icu tld badges over 6 months and the estimated cumulative radiation exposure to the resident doctors per year .\nthe control tld placed in the department of anesthesia served as a measure of baseline atmospheric ionizing radiation , and all other values are reported above this baseline .\nthe results of dosimetric analysis of residents tlds during the two phases are shown in table 2 .\nreadings from tlds placed in the nursing station and doctors ' duty room during both phases were immeasurable .\nthe mean values in the first and last 3 months were 0.052 and 0.069 msv respectively , though the highest individual value approached 0.1 msv .\nsince this was recorded in a 3 month period , the projected reading for similar exposure throughout the year , even assuming a 24 h duty period , would be 0.4 msv , which is well below the safety limit of 20 msv / year .\nrevolutionary progress in the field of medical imaging has given a big leap to advances in medical diagnostics and therapeutics .\nthis development has also infiltrated the field of critical care medicine , and radio - diagnosis and interventional radiological procedures now play a key role in the management of critically ill patients . while this advancement offers the advantages of rapid bedside diagnosis , and cost - effective and minimally invasive treatment options to critically ill patients , it carries the danger of exposure of patient and physician to radiation .\nthe detrimental effects of exposure to even low - level ionizing radiation have always been known ; however , there is renewed concern because of its wide - spread use in medical radio - diagnosis and therapeutics in critically ill patients .\nit is , therefore , natural that there may be concerns about the long - term effects of radiation exposure to doctors working for long periods of time in the icu .\nin addition , where icu doctors are responsible for transport of patients to the radiology suite , the extent of radiation exposure is increased .\nit is reassuring that the results of our study confirm that the extent of radiation exposure to critical care physician during the course of his duty is well within acceptable limits .\nthere is considerable literature on occupational hazards of radiation exposure among radiologists ; however , it is difficult to directly extrapolate the conclusions of these studies to the icu .\nworking conditions in the icu do not mimic those in radiology suites - working hours tend to be long , there is a need to accompany mechanically ventilated and hemodynamically unstable patients inside the radiology suite for procedures , and icu doctors may sometimes take radiation safety norms lightly .\na study performed in a trauma icu ( ticu ) has concluded that radiation exposure is not a significant occupational hazard for the ticu personnel .\nsimilarly , another study looked into the radiation exposure to icu nurses and found that the exposure was well below the permissible level .\nthe strength of our study is that it was planned in a more pragmatic way - apart from bedside radiological procedures , we also took into account the radiation exposure to icu residents accompanying the patient to radiological suites for diagnostic and therapeutic procedures\n. ionizing radiation from fluoroscopy in the ct scan or interventional radiology suites may be significant and were not considered in the previous studies .\nwe also tried to measure the amount of scattered radiation within the icu and the pacu , which contributes to overall radiation exposure .\neven after taking these additional sources of radiation exposure into account , we found that the cumulative radiation exposure was negligible .\nthe number and types of bedside and out - of - icu radiological procedures can vary on a day - to - day basis according to the case - mix of the icu population , and this may affect the overall radiation exposure ; however , this study was carried out over a period of 6 months , and the data obtained would have been adequately representative .\nthe other limitation relates to the generalizability of the study ; differences in the types of cases , working pattern of resident doctors , quality and maintenance of radiological equipment between hospitals may restrict the applicability of these results to other hospitals .\nhowever , given the large margin of safety that our study has shown , it is unlikely that exposure levels would be dangerously high in any other setting .\nthough , with advances in technology , the number and types of radiological procedures performed on patients are likely to increase . furthermore , there is a growing trend toward using radionuclide - based positron emission tomography scans for diagnostic procedures in critically ill patients especially when they are admitted to icu during their diagnostic work - up .\nsome of these patients may continue to emit radiation long after their procedures are completed .\nthough none of these patients featured in our study , it will add to the radiation exposure to doctors .\nthe results of this study do not in any way underrate the need to follow safety precautions , while carrying out radiological procedures in critically ill patients .\nthe levels of exposure found in this study should be interpreted bearing in mind that standard protection norms were used by all personnel involved in the study . with these precautions in place ,\nradiation exposure to doctors managing critically ill patients in the icu is minimal and acceptable .\nliterature on radiation exposure among icu doctors is scarce . in addition to bedside radiological procedures , the risk of exposure may be increased if the same doctors accompany icu patients for out - of - icu radiological investigations .\nhowever , we found that if standard safety precautions were followed , cumulative radiation exposure to icu resident doctor was well within permissible limits and was not the cause of concern and hence routine personal dosimetric monitoring is not needed for residents in icu .\nhowever , in view of changing practice , there is a need to repeat such audits periodically to monitor radiation exposure .", "answer": "background and aims : with the expanding use of diagnostic and therapeutic radiological modalities in critically ill patients , doctors working in intensive care units ( icus ) are increasingly exposed to ionizing radiation . \n this risk of radiation exposure occurs not only during bedside radiologic procedures , but also when icu physicians accompany patients to radiology suites . \n the aim of this study was to quantify levels of radiation exposure among medical professionals working in the icu.materials and methods : the study was carried out prospectively over 6 months in the icu of a tertiary - referral cancer hospital . \n two teams consisting of 4 icu resident doctors each were instructed to wear thermoluminescent dosimeters ( tlds ) during their duty shifts . \n standard radiation protection precautions were used throughout the study period . \n tlds were also placed in selected areas of the icu to measure the amount of scattered radiation . \n tlds were analyzed at the end of every 3 months.results:the readings recorded on tlds placed in the icu were almost immeasurable . \n the mean value of residents ' radiation exposure was 0.059 msv , though the highest individual reading approached 0.1 msv . \n the projected maximum yearly radiation exposure was 0.4 msv.conclusions:if standard radiation safety precautions are followed , the cumulative radiation exposure to icu resident doctors is well within permissible limits and is not a cause of concern . \n however , with the increasing use of radiological procedures in the management of critically ill patients , there is a need to repeat such audits periodically to monitor radiation exposure .", "id": 751} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noral melanoma is an extremely rare tumor arising from uncontrolled growth of melanocytes found in the basal layer of oral mucous membrane .\nit occurs between 30 and 90 years of age , with a higher incidence in the 6th decade with a mean age of 56 years .\nit is having a higher prevalence in yellows , blacks , japanese , and indians of asia due to more frequent finding of melanin pigmentation in oral mucosa of these races .\ngreen et al . described criteria for diagnosis of primary oral melanoma which includes demonstration of melanoma in the oral mucosa , presence of junctional activity , inability to demonstrate extraoral primary melanoma .\na total of 80% to 90% of oral malignant melanoma arises in the mucosa of maxillary jaw with a majority occurring on the keratinized mucosa of hard palate and gingiva .\nclinically , it is easy to diagnose them as these are pigmented ones and have irregular shape and outline .\nthese are mostly asymptomatic and detected only when there is ulceration or hemorrhage of the overlying epithelium\n. the delayed detection may be the cause for the poor prognosis with a 5-year survival being between 15% and 38% .\nthe purpose of this article is to present a case of oral malignant melanoma , as well as to emphasize the necessity for early recognition and treatment of this lesion .\na 48-year - old male patient reported to the department of oral medicine and diagnosis with chief complaint of pain and swelling in the upper right gums .\nthe clinical examination revealed a large mass of 8 3 cm in dimension on buccal aspect of right maxillary alveolus involving marginal , attached , and interdental gingiva [ figure 1 ] .\nanteriorly , it extends from the gingiva of mesial surface of 22 , to the gingiva in relation to 17 posteriorly .\n13 was missing and 12 was displaced laterally ; while , 11 , 12 , and 21 exhibited mobility . primary oral malignant melanoma extending from 22 to distal aspect of 17 the palpatory findings revealed a firm consistency of lesion with mild pain .\na complete examination of the lesion was done and no other primary site of the lesion was found .\ncorrelating all clinical features , diagnosis of primary malignant melanoma of oral cavity was made and the patient was referred for further investigations .\na computed tomography examination of neck , chest , abdomen , and bone scanning and ultrasounds of liver and kidney were normal excluding any diagnosis of distant metastasis .\nan incisional biopsy was done for the lesion under local anesthesia and the specimen was sent for histopathologic examination .\nthe gross examination of tissue revealed a mass of 2 mm 3 mm 1 mm in size , which was black in color and firm in consistency .\nthe hematoxylin and eosin - stained section showed a melanin - producing tumor , consisting of atypical irregularly elongated spindle and oval - shaped melanocytes , exhibiting uniformly dark , enlarged and irregular nuclei [ figure 2 ] . in the superficial layers of the tissue , a junctional nevus with pigmentation\nthe diagnosis of an invasive melanoma arising most likely from a pre - existing junctional nevus was made and the patient was referred to the oral and maxillofacial surgery clinic for required therapy . as per the traditional approach , partial maxillectomy of the right side was performed . to reduce the defect and to reconstruct alveolus ,\nmicrovascular fibula flap was used . the orbital floor near to maxilla was reconstructed with the help of premolded titanium mesh .\nthe histologic examination of the specimen confirmed the initial diagnosis of an invasive melanoma of the oral mucosa .\nthe patient has been followed - up with no evidence of recurrence or metastasis either clinically or radiographically , 11 months after the tumor 's resection .\nthe hematoxylin and eosin stained section shows melanoma with invasive pattern showing large cells with pleomorphic vesicular nucleus and brown pigment ( 40 ) the hematoxylin and eosin stained section shows stratified squamous keratinized epithelium with in situmelanotic pigment growth ( 10 )\nit has no known predisposing factors and is difficult to diagnose and manage . differentiating it from a metastatic melanoma is often challenging .\nthe first symptoms of oral melanoma described by berthelsen were those of asymptomatic swelling and occasional bleeding , where he found that only 2 ( 14% ) patients had a pain .\nbecause most of the melanomas are painless in their early stages , the diagnosis is often unfortunately delayed until symptoms resulting from ulceration , growth , or bleeding are noted .\nthe pain may be the later manifestation in melanoma as in our case that again could cause delay in seeking treatment . on gross appearance ,\nthe tumors on the palate are usually flat , with a varying degree of thickness .\nmicroscopically , the tumor cells present themselves as densely packed , large epithelioid cells with eosinophilic cytoplasm . the melanin pigment , which is located intra or extracellularly , may be abundant , but may be sparse or even absent at the light microscopic level . the prognostic value of various levels of invasion , as established in the clark 's classification , does not apply for mucosal melanoma because of the absence of histologic landmarks , which are analogous to the papillary and reticular dermis . the staging systems that are applied to cutaneous melanoma are not applicable to mucosal melanomas . the american joint committee on cancer\nthe generally followed guideline is a clinical classification stage i clinically localized disease , stage ii regional lymph node disease , and stage iii - distant disease .\nthe tumor thickness is a reliable prognostic indicator for survival . in this case , the patient was in stage i. westbury describes a clinical classification as follows : 1only primary tumor present , and 2metastasis present , 2a adjacent skin involved , 2b adjacent lymph nodes involved , and 2ab adjacent skin and lymph nodes involved .\nthus , according to these systems specification , our patient was in stage i. the etiology of malignant melanoma is essentially unknown\n. tobacco use and chronic irritation from ill - fitting dentures have been considered as possible risk factors , but the evidence is weak .\nthe cause could also be related to our patient as he was having the history of smoking from last 15 years .\nbut most of the malignant melanomas arise de novo , from apparently normal mucosa , and about 30% are preceded by oral pigmentations for several months or even years .\nsome melanoma - associated antigens become expressed during transformation process from a benign melanocytic nevus to melanoma ; the majorities of these are related to the melanin production process and most are hla restricted .\na recent study demonstrates that the loss of heterozygosity at 12p13 and p27kip1 protein expression contributes to melanoma progression .\ncytogenetic analysis and evaluation of melanocyte - specific gene-1 ( msg-1 ) appears to be very helpful for understanding the pathogenesis of oral malignant melanoma .\nthe current guidelines for the surgical management of primary cutaneous melanoma recommend a diagnostic excisional biopsy of the lesion followed by a wide local excision where the diagnosis is proved .\nhowever , in oral cavity , the size of the lesion or anatomic limitations , particularly the presence of teeth , may preclude the taking of excisional biopsy .\nyounes et al . proposed to take an excisional biopsy with a 12 mm margin for small lesions in amenable locations , but incisional biopsy , through the thickest or the most suspicious part of the tumor , in case of a large lesion or a location in sites where an excisional procedure would involve extensive and militating surgery .\nusually oral malignant melanoma can be diagnosed with confidence on hematoxylin and eosin stained sections .\nif pigment is completely absent ( amelanotic melanoma ) , immunohistochemical stains are of significant help .\nuseful markers include s-100 protein , gp 100 ( hmb-45 ) , and mart-1 ( melan - a ) .\nit has always been suggested that cutting into malignant neoplasm during incisional biopsy could result in accidental dissemination of malignant cells within adjacent tissues or blood or lymphatic stream with subsequent risk of local recurrence or regional or distant metastasis .\ndid find a somewhat reduced survival rate in patients with melanoma who had incisional biopsies but against the studies done by lederman and sober where they found no correlation in patient 's prognosis with incisional and excisional biopsies .\ndistant metastasis to the lungs , brain , liver , and bones are frequently observed .\nthe treatment of oral malignant melanoma is still controversial and there is no census regarding the best therapeutic approach .\ndata from several studies indicate radical resection of the primary as the treatment of choice .\nregression in melanoma is a well - recognized phenomenon and may account for many of the cases of metastatic melanoma with occult primaries . partial regression of melanoma is relatively common , but complete regression is quite rare and relatively few cases are well documented .\na further feature of regression is its association with poor rather than a good prognosis .\nthe rather nonspecific features of regressed melanoma ( apparently inflammatory nodules , depigmented patches , and flat or slightly depressed scars ) are easily missed or discounted unless the patient had noticed the regression . from the prognostic point of view , clinical stage at presentation is probably the most important factor in determining the outcome .\nit has been found by liu et al . that thickness of the tumor , cervical lymph node metastasis , presence or absence of ulceration , and the anatomic sites are all independent risk factors .\nit has been calculated that nodal metastasis reduces the mean survival time from 46 to 18 months .\nfurthermore , a tumor thickness greater than 5 mm , presence of vascular invasion , necrosis , polymorphous tumor cell morphology , and inability to properly resect the lesion with negative margins have been associated with poor survival in patients with primary melanomas of head and neck region .\ndespite the improvement of surgical techniques and the introduction of new chemotherapeutic agents , prognosis of this malignancy remains poor .\nthe generally advanced stage of the tumor at initial diagnosis leads to a poorer survival of patients with mucosal melanomas as compared with patients with cutaneous melanomas and presence of vertical growth phase are associated with median survival rate .\nanalysis of published cases and recognition of new ones may be helpful in establishing definite classification and proposing clinical features that would facilitate its early diagnosis as a prerequisite for timely treatment and better prognosis of this rare pathology .", "answer": "primary oral melanoma is a rare neoplasm of melanocytic origin , accounting for 0.5% of all oral malignancies . \n the chameleonic presentation of a mainly asymptomatic condition , rarity of this lesion , poor prognosis , and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health provider . \n here is a case report presenting a malignant melanoma of oral mucosa in 48-year - old male patient on maxillary gingiva . \n the lesion was removed by partial maxillectomy and patient is disease free after 11 months of regular followup . \n this case provides an example of how dental clinicians play a major role in the identification of pigmented lesions of oral cavity and also emphasize on the fact that any pigmented lesion detected in the oral cavity may exhibit potential growth and should be submitted to biopsy to exclude malignancy .", "id": 752} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nisolated involvement of the appendix in crohn 's disease is reported to be 0.2% to 1.8% , and is usually associated with ileocaecal crohn 's disease in 25% of ileal and 50% of caecal disease .\nwhile appendicitis in a patient who was previously diagnosed to have ileocaecal crohn 's may be managed with appendicectomy and ileocaecal resection , appendicectomy alone when performed for appendicitis in a patient with unsuspected ileocaecal crohn 's disease could lead to postoperative complications including enterocutaneous fistula .\na young female patient who underwent appendicectomy elsewhere for acute appendicitis presented to us with a persistent enterocutaneous fistula of 6 weeks duration .\nshe had complained of general ill health and occasional altered bowel habits for 6 months prior to the acute appendicitis presentation .\nour investigations , including a ct scan , suggested the possibility of ileocaecal crohn 's disease .\nshe underwent excision of the enterocutaneous fistula and ileocaecal resection , and histopathology of the resected specimen confirmed crohn 's disease . in the postoperative period she received mesasalazine .\nwhen last seen 2 years later during her regular follow - up , she was found to be in good health .\nthe possibility of ileocaecal crohn 's disease should be considered in patients presenting with unexplained postoperative enterocutaneous fistula following appendicectomy .\na high index of clinical suspicion is required to make a prompt diagnosis and institute appropriate further treatment in form of ileocaecal resection .\ncrohn 's disease is a chronic inflammatory condition that may involve the entire gi tract .\nhistological features include granuloma , lymphoid aggregates , fissures and ulcers extending into muscularis propria , and transmural inflammation .\ncrohn 's disease has been reported to be the cause of acute appendicitis in 0.2% to 1.8% of all the appendicectomies in some series .\noperations described in the literature for crohn 's disease of the appendix include appendicectomy with caecectomy and ileocaecal resection .\nhowever , patients who undergo appendectomy alone are at the risk of complications including enterocutaneous fistula in 34% to 58% of the cases\na 24-year - old unmarried female patient presented to us with a persistent fistula in the right iliac fossa following an appendicectomy done in another hospital 6 weeks previously . on further questioning , she informed us that she had presented to this hospital with a 2-week history of abdominal pain , confined to the right lower abdomen .\nshe complained of general ill health and occasional altered bowel habits for 6 months prior to this acute episode .\nan enquiry with the doctors who had initially seen her revealed that at the time of presentation for acute appendicitis she was quite unwell with fever , tachycardia , and dehydration .\nher abdomen was tender all over with guarding , more pronounced over the right lower half .\nan x - ray of her abdomen showed a few fluid levels and an ultrasound scan revealed free fluid in the abdomen with an associated right iliac fossa mass .\na diagnosis of pelvic peritonitis secondary to acute appendicitis was made by the physicians , and she was taken up for surgery after adequate resuscitation .\nthere was pus in the abdomen with an appendicular mass , and the appendix appeared oedematous , thickened , and congested .\nthe abdomen was closed after placing a drain , which was removed on the 3 post - operative day . in spite of antibiotic administration\nshe was managed conservatively with antibiotics and anti - inflammatory medication and eventually improved , except for a persistent purulent discharge from the wound .\nshe then decided to seek our opinion and was admitted under our care for further investigation and management .\nthe appendicular histopathology was retrieved from the previous hospital and revealed transmural inflammation with granulomas suggestive of crohn 's disease .\na computerized tomography ( ct ) scan of the abdomen carried out in our hospital showed pericaecal collection with an inflammatory mass in front of the caecum ( fig .\nthe abdomen was surgically explored through the previous incision after excising the fistula leading into the caecum . an inflammatory mass associated with the caecum was noted .\nthe appendicular stump had not healed , and was draining into a cavity which was communicating with the wound , indicating a complex enterocutaneous fistula . a limited right hemicolectomy was carried out and continuity established with a primary anastomosis of macroscopically - appearing healthy bowel of the ascending colon and terminal ileum .\na specimen of the resected caecum revealed the cobblestone appearance of the mucosa , strongly suggesting the possibility of underlying caecal crohn 's disease ( fig .\nthe histology was reported as inflammatory bowel disease ( ibd ) consistent with crohn 's disease ( fig .\nshe was referred to a gastroenterologist and was being treated with mesasalazine and a regular annual colonoscopy .\nwhen last seen at two years post - surgery she continued to remain in good health . limited right hemicolectomy specimen showing the cobble stone appearance of the mucosa typical of crohn 's disease .\ncrohn 's disease may involve the appendix by extension from the terminal ileum or the caecum and present as an acute or sub - acute appendicitis[15 ] .\ncrohn 's disease limited to the appendix usually affects young adults in their 20s and 30s , although it is not limited to this age group and can occur at any age .\nthe clinical presentation is variable , with acute right iliac fossa pain suggestive of acute appendicitis in about 85% of patients , and chronic pain and a palpable mass in the right iliac fossa in about 25% of patients .\nwhen the preoperative diagnosis is acute appendicitis , crohn 's disease should be suspected when an atypical or protracted clinical course is present in a patient prior to the appendicitis , particularly in areas where crohn 's disease is prevalent .\ncrohn 's disease is diagnosed by a combination of clinical manifestations and radiological findings including barium studies , showing string strictures , fissures , and fistula in the ileum and caecum .\nrecently , gray scale sonography and color doppler - flow features have been used in diagnosing crohn 's disease . when the disease is located atypically in the appendix ,\nmacroscopically , the appendix will be seen to be enlarged , swollen and adherent to the surrounding structures , these findings being secondary to chronic inflammation .\nhistologically , the disease is characterized by transmural inflammation with thickening of the appendiceal wall , epitheloid granulomas , lymphoid aggregates , and mucosal ulceration .\nother histological features are multinucleated giant langherhan 's cells , crypt abscess , neural hyperplasia and lymphangiectasia .\ndifferential diagnosis includes the presence of foreign bodies and diverticulitis of the appendix , which also give rise to chronic granulomatous inflammation with induration and fibrosis of the appendiceal wall , and granulomatous disease of unknown aetiology such as appendiceal sarcoidosis , which is rare and often accompanies systemic disease .\ndifferential diagnosis should also include infectious diseases such as tuberculosis , actinomycosis and yersenia infection .\na rare fungal infection such as histoplasmosis or blastomycosis , or a parasitic infestation such as schistosomiasis or enterobius vermicularis infestation can elicit an appendiceal granulomatous reaction .\nthe diagnostic difficulty arises when a patient undergoes an appendicectomy for suspected acute appendicitis and the surgeon unexpectedly encounters ileocaecal pathology whose nature is difficult to ascertain in an emergency situation . in view of this , a definitive treatment in the form of ileocaecal resection for conditions like crohn 's disease may be difficult to carry out . while a frozen section may be helpful to differentiate some of these conditions it may not always be feasible in an emergency situation . if crohn 's disease of the appendix is suspected and is limited to the appendix then appendicectomy alone is a routine surgical procedure with very low intraoperative or postoperative mortality and a low rate of fistula formation.the postoperative enterocutaneous fistula incidence rate in crohn 's disease restricted to appendix alone has been reported to be 3.5% , whereas in patients with crohn 's disease of the ileocaecal segment , as in our patient , the postoperative enterocutaneous rate rises to 34% to 58% .\nweston et al reported that the majority of the patients whose first presentation of crohn 's disease simulates appendicitis and who undergo appendicectomy alone leaving the ileocaecal segment in place to be treated medically , returned postoperatively within 3 years with symptoms . a significant percentage ( 38% ) of these patients returned within one year and most of them ( 77% ) were frequently ill with their disease in the interim period .\npatients who had an ileocolic resection at the time of the initial operation did not require early reoperation , did not develop short bowel syndrome , and did not have significant postoperative complications .\nin the postoperative period these patients receive medical therapy to keep the disease quiescent such as salazopyrine , 5-asa , prednisilone , and azothioprine.crohn's disease - related fistula have also been treated with infliximab with some success . despite improvements in medical therapy , between 70% to 90% of the patients with crohn 's disease will eventually require surgical intervention , and approximately half of these will require additional operations . because of the high risk of reoperations and a relatively young age at the time of first operation , a minimally invasive approach has recently been used to carry out the ileocolic resections .\na recent meta - analysis of laparoscopic ileocolic resection has revealed a shorter hospital stay compared to open resection , while the morbidity rates were equal and conversion rates were acceptable .\nthe average interval between surgery and recurrence after appendicectomy for crohn 's disease of the appendix is 4 years , after which some claim the recurrence rate to be almost nil .\nhowever , others have reported a recurrence rate of 10% over an 8-year follow - up and is much higher in patients with crohn 's disease of the appendix associated with ileocaecal crohn 's disease .\nmost authors recommend periodic surveillance visits with radiological and endoscopic examination of the small intestinal and colon for a period of at least 3 years to promptly detect recurrence .\nhowever , others claim that patients with crohn 's disease should be followed for 10 years , and if disease free by then are considered cured .\ncrohn 's disease of the appendix is usually associated with crohn 's disease of the ileum and caecum .\nappendicectomy will suffice in those who present subacutely , are diagnosed preoperatively by clinical signs , and radiographic evidence shows that the disease is restricted to the appendix alone .\nhowever , in the presence of ileocaecal involvement , resection of the ileocaecal segment may be required to prevent postoperative complications of enterocutaneous fistula . while patients who develop enterocutaneous fistula post - appendicectomy in an unsuspected crohn 's disease case have been treated with infliximab with some success , the majority of the patients required ileocaecal resection . moreover ,", "answer": "context : isolated involvement of the appendix in crohn 's disease is reported to be 0.2% to 1.8% , and is usually associated with ileocaecal crohn 's disease in 25% of ileal and 50% of caecal disease . \n while appendicitis in a patient who was previously diagnosed to have ileocaecal crohn 's may be managed with appendicectomy and ileocaecal resection , appendicectomy alone when performed for appendicitis in a patient with unsuspected ileocaecal crohn 's disease could lead to postoperative complications including enterocutaneous fistula.case report : a young female patient who underwent appendicectomy elsewhere for acute appendicitis presented to us with a persistent enterocutaneous fistula of 6 weeks duration . \n she had complained of general ill health and occasional altered bowel habits for 6 months prior to the acute appendicitis presentation . \n our investigations , including a ct scan , suggested the possibility of ileocaecal crohn 's disease . \n she underwent excision of the enterocutaneous fistula and ileocaecal resection , and histopathology of the resected specimen confirmed crohn 's disease . in the postoperative period she received mesasalazine . when last seen 2 years later during her regular follow - up , she was found to be in good health.conclusion:the possibility of ileocaecal crohn 's disease \n should be considered in patients presenting with unexplained postoperative enterocutaneous fistula following appendicectomy . \n a high index of clinical suspicion is required to make a prompt diagnosis and institute appropriate further treatment in form of ileocaecal resection .", "id": 753} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntestosterone is essential for the normal growth and development of the prostate gland and is also a possible risk factor for prostate cancer .\nhuggins and hodges 's seminal work in the 1940s first demonstrated the hormone dependence of prostate cancer , consequently establishing testosterone as a key therapeutic target for managing prostate cancer .\nandrogen deprivation therapy to lower the serum testosterone level remains a standard treatment for advanced disease to the present day .\nisbarn et al 's recent studies , however , show a result opposite that of huggins and hodges , implying that testosterone neither increases the risk of prostate cancer nor causes cancer recurrence in men who have been treated successfully for prostate cancer .\na recent study by morote et al showed that prostate cancer risk and tumor aggressiveness are unrelated to serum testosterone .\nother recent epidemiologic studies also have found no association between testosterone and prostate cancer [ 6 - 10 ] . our main objective was to analyze the relationship between serum testosterone , prostate - specific antigen ( psa ) , and prostate cancer risk in high - risk patients .\nthe study population consisted of 120 men with a psa level of 10 ng / ml or higher .\nthe data were collected from january 2008 to january 2010 . to determine the relationship between testosterone , psa , and prostate cancer risk in a high - risk group , we limited our study population to men with a psa level of 10 ng / ml or higher .\nwe excluded from this analysis men who were taking medications known to lower psa , such as finasteride or dutasteride .\ntwelve cores were obtained and two extra biopsies were taken if hypoechoic or otherwise suspicious areas were noted on ultrasound .\nserum testosterone levels were measured by using a solid - phase competitive chemiluminescent enzyme immunoassay with the advia centaur immunoassay system ( bayer health care , chicago , il , usa ) .\nwe classified the men as hypogonadal if their serum testosterone level was < 300 ng / dl , according to the criteria used by rhoden et al . for possible correlation between serum testosterone , psa , and prostate cancer , we included age , psa density ( psad ) , prostate volume , and gleason score for patients with prostate cancer .\nstatistical analysis was performed by using the student 's t - test , the pearson correlation test , simple linear regression , and binary logistic regression . odds ratios with 95% confidence intervals ( cis ) for psa , psad , serum testosterone , and age were determined to predict prostate cancer risk .\nall data are presented as the mean2 sd to define and characterize quantitative variables and as percentages to characterize qualitative variables ; we considered a p - value<0.05 to be statistically significant .\nout of 120 patients , the samples of 85 ( 70.1% ) patients were diagnosed as benign and those of 35 ( 29.2% ) patients were diagnosed as being prostate cancer .\nthere was no significant difference in the patient 's average age , psa , prostate volume , or testosterone between patients without and those with prostate cancer .\nonly psad differed significantly between the two groups ( t - test , p=0.012 ) ( table 1 ) .\nhypogonadal and eugonadal men did not differ significantly in cancer detection rate ( 30.2% vs. 32.0% , respectively ) .\nthe testosterone level did not differ significantly between patients without and those with prostate cancer in either hypogonadal ( 248.1650.41 ng / dl vs. 251.3543.61 ng / dl , respectively ) or eugonadal ( 501.52137.06 ng / dl vs. 506.22126.40 ng / dl , respectively ) men ( t - test , p>0.05 ) .\ntestosterone was unrelated to age , psa , psad , or prostate volume in both men without and those with prostate cancer , and prostate cancer aggressiveness also was unrelated to serum testosterone in prostate cancer patients ( p>0.05 ) ( table 2 ) .\nthe binary logistic regression also confirmed that none of the variables used in this study was an independent predictor of prostate cancer risk for men with a psa level > 10 ng / ml ( p>0.05 ) ( table 3 ) .\nfurther evaluation with simple linear regression confirmed that testosterone and psa did not show any correlation ( p>0.05 ) ( fig .\nwhen we divided the patients into 11 groups according to their testosterone level , within a 150 ng / dl range , prostate cancer prevalence did not change as the testosterone level increased ( p>0.05 ) ( table 4 ) .\nin men , the leydig cells in the testes produce approximately 90% of testosterone ; the adrenal glands produce the rest .\ntestosterone plays a key role in the development of male reproductive tissues such as the testes and prostate gland . under testosterone influence , the prostate gland experiences two main growth periods .\nthe first occurs early in puberty , when the prostate doubles in size . at around age 25 ,\nwhen the prostate is growing , testosterone is converted into dihydrotestosterone ( dht ) , which is the androgen receptor 's major activator .\nafter dth binds to androgen receptors , it translocates to the nucleus , where it mediates the transcriptional activation of target genes .\nthese androgen - stimulated changes in gene expression promote cellular growth , which often results in benign prostatic hyperplasia in elderly men .\nlong - term cessation of the prostate 's exposure to androgen appears to protect against the development of cancer , but no dose - response relationship between testosterone level and cancer risk has been established .\nthe prostate cancer risk for men with a testosterone concentration in the normal range remains unclear .\nrecent chemopreventive trials with 5-alpha - reductase inhibitors show the role of testosterone in prostate cancer development .\nfinasteride reduced the risk of prostate cancer by 24.8% compared with a placebo in healthy men .\nrecently , the reduce study showed that dutasteride also reduced the risk of prostate cancer by 23% compared with a placebo in healthy men .\nhuggins and hodges first showed the effect of testosterone on prostate cancer patients in 1941 .\nthey showed the hormonal responsiveness of prostate cancer by reporting that markedly reducing the testosterone level by castration and estrogen treatment caused metastatic prostate cancer to regress , and injecting testosterone caused prostate cancer to grow . in 1995\nwu et al found that the distribution of dihydrotestosterone - to - testosterone ratios parallels both the incidence of and mortality from prostate cancer .\nthe demonstration that androgen suppression effectively treats advanced prostate cancer , and the fact that elevated serum androgen levels might predispose people to prostate cancer , have attracted persistent interest .\nhowever , a recent study refuted any connection between elevated testosterone levels and increased prostate cancer risk .\nendogenous hormones and prostate cancer collaborative group et al meta - analyzed the serum concentrations of sex hormones from subjects in 18 prospective studies that included 3,886 men with incident prostate cancer and 6,438 control subjects .\nthey concluded that endogenous hormones , including testosterone , were not associated with prostate cancer .\nmorote et al recently conducted another study of 478 patients , all of whom were assessed by trus - guided prostate biopsy because of an abnormal digital rectal examination , psa > 4 ng / ml , or both .\nthey found no difference in serum testosterone level between patients with and those without prostate cancer and concluded that the serum testosterone level was not associated with prostate cancer risk or aggressiveness .\nan animal study by morgentaler and traish showed that beyond a certain serum testosterone concentration , androgens have a limited ability to stimulate prostate cancer growth .\nsubsequent increases in serum testosterone levels beyond that concentration did not stimulate the prostate because the binding capacity of the intra - prostatic androgen receptors had been saturated .\nour results are similar to those of the above studies even though we limited our study population to patients with psa > 10 ng / ml . we found that the serum testosterone level at the time of diagnosis was unrelated to psa and prostate cancer risk and aggressiveness in both hypogonadal and eugonadal patients .\nideas about the interaction between testosterone and prostate cancer have changed considerably over the past decade . like our study , most recent epidemiologic studies have found no association between testosterone and prostate cancer [ 6 - 10 ] .\na few studies published during the past decade contrast with our results , however , and show that low testosterone levels seem to be related to an increased risk of prostate cancer and tumor aggressiveness , such as a high gleason score [ 23 - 28 ] . in our study , we compared age , psa , prostate volume , and psad with testosterone .\nonly a known prostate cancer predictor , psad , showed a significant difference between patients with and those without prostate cancer , even in high - risk patients with a psa level of 10 ng / ml or higher .\npatients without prostate cancer had relatively lower psa and larger prostates than did patients with prostate cancer .\nhowever , our binary logistic regression showed that psad was unsuitable as an independent predictor of prostate cancer risk in men with a psa level of 10 ng / ml or higher .\nwe measured the serum testosterone level in the patients only once , before their biopsy was done .\nsecond , we checked only their total testosterone level and were unable to check their free testosterone level .\n, the present study found that the serum testosterone level at the time of diagnosis was unrelated to psa and prostate cancer risk and aggressiveness . because testosterone levels change with age and time , a prospective study with long - term testosterone monitoring is required to find a relationship between testosterone and prostate cancer .\nour results show that the serum testosterone level at the time of diagnosis was unrelated to psa and prostate cancer risk and aggressiveness .\nadditional studies with long - term follow - up are needed to explain the possible mechanism and relationship between testosterone , prostate cancer , and psa .", "answer": "purposetestosterone is essential for the prostate gland 's normal growth and development and is also a possible risk factor for prostate cancer . \n this study 's aim was to determine the significance of serum testosterone for prostate - specific antigen ( psa ) elevation and prostate cancer prediction in high - risk men.materials and methodsthe study included 120 patients with psa > 10 ng / ml who underwent a transrectal - prostate biopsy . \n serum testosterone , prostate volume , and psa density ( psad ) were checked in all patients . \n patients were divided into two groups , patients with and those without prostate cancer ; and testosterone - related factors , prostate volume , psa , psad , age , prostate cancer prediction rate , and cancer aggressiveness were evaluated.resultsthirty-five patients ( 30.2% ) were confirmed as having prostate cancer . the average serum testosterone level in patients without and in those with prostate cancer was 452.25154.62 ng / dl and 458.10158.84 ng / dl , respectively ; average psa was 17.589.02 ng / ml and 18.626.53 ng / ml , respectively ; and average age was 69.027.52 years and 70.697.02 years , respectively ( p>0.05 ) . hypogonadal and eugonadal \n patients showed no significant difference in cancer prevalence ( 30.3% vs. 32.0% , respectively ) . \n the testosterone level did not differ significantly in patients with and those without prostate cancer in either hypogonadal or eugonadal men ( p>0.05 ) . \n serum testosterone showed no correlation with psa , psad , or age in either group ( p>0.05 ) and was unrelated to prostate cancer risk or aggressiveness ( p>0.05).conclusionsin our study 's results , serum testosterone at the time of diagnosis was unrelated to psa elevation , prostate cancer risk , and aggressiveness .", "id": 754} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nposttraumatic avascular necrosis ( avn ) of the scaphoid is a common complication probably due to the precarious blood supply .\nthe rate of incidence is about 13% to 40% and almost all are seen in the proximal fragment [ 2 , 3 ] .\ncareful review of the literature revealed six cases of distal avn in three studies [ 4 , 5 , 6 ] .\nthe diagnosis of avn of the scaphoid is made by combining the mri findings with direct observation of the punctuate bleeding during the operation .\nhowever , the diagnosis of avn is suspicious in these cases , as mri investigation had been performed in one case and preoperative bleeding was observed in the other .\nhere , we report four new cases , all with the correlation of mri and punctuate bleeding .\nthe series consisted of four patients aged 29 , 33 , 53 and 57 years .\nall had a history of scaphoid fracture following a fall on an outstretched hand 35 years ago , and all had been treated by casting before .\nradiographic examination revealed suspected areas , such as sclerosis and/or cystic changes , on the distal pole of the scaphoid ( figure 1 ) and mri views were identical with avn of the distal pole , showing hyperintense changes ( figure 2 ) . \n\ntourniquet was deflated in order to observe punctuate bleeding ; it was observed in three cases and the patients were treated by bone grafting and wire fixation ( figure 3 ) in the remaining , there was no punctuate bleeding despite drilling and the scaphoid was excised and radial advancement osteotomy ( figure 4 ) was performed . \n\ntreated by bone grafting and wire fixation . \n \n scaphoid was excised and radial advancement osteotomy . \n \nall patients were evaluated by quick disabilities of shoulder , arm , and hand score 711 years after the operation by telephone interview . according to this score , 11 questions related to daily living\nposttraumatic avn of the scaphoid occurs as a result of impairment of the vascular supply to the involved bone fragment .\nseveral studies had demonstrated a strikingly poor blood supply to the proximal pole , particularly in comparison with the abundant supply to the distal two - thirds of the scaphoid [ 1 , 2 ] .\nreview of the literature revealed six cases in three reports [ 4 , 5 , 6 ] .\n, avn in the distal fragment occurs if the volar vessel is damaged and the fracture line is distal to the line of entry of the dorsal vessels .\nanother explanation maybe the anomalous different vascularization of the distal pole [ 5 , 6 , 9 ] .\nthe diagnosis of avn of the scaphoid was made by combining the mri findings with direct observation of the punctuate bleeding during the operation .\nhowever , there is no such approach in the previously described cases [ 4 , 5 , 6 ] . in the case of sherman et al . , mri was not available and there was no chance to observe bleeding , as the patients had refused surgical treatment .\nsimilarly , in the case of the garg et al . , although mri suggested avn , the patient had been treated conservatively , so there was no chance for punctuate bleeding , and the fracture united .\nthe diagnosis is also suspicious in this case as no correlation was possible and the fracture had healed .\naccording to herbert , avn means irreversible necrosis or death of bone and healing is impossible .\nonly one case had been operated . in this case , the authors had confirmed avn by the pinning attempt that had failed .\nthere seems no such method for the diagnosis of avn , so the diagnosis is again in doubt . in our opinion\n, all these cases should be labeled as suspected avn . in three of our cases , although preoperative mri suggested avn ( figure 2 ) , punctuate bleeding was observed during the operation and all were treated by pinning and grafting and healed uneventfully . in those cases , the appearance of avn was probably due to the normal marrow of bone that has not been established yet , but bleeding was observed due to revascularition . in the remaining case , mri suggested avn along with lack of punctuate bleeding and scaphoid was excised and radial advancement osteotomy was performed . in conclusion , all six cases reported before [ 4 , 5 , 6 ] , and three of our cases that were treated by pinning and had healed , were not real avn or the diagnosis was doubtful .\nso our fourth case seems to be a unique case of distal pole avn of the scaphoid in the literature .", "answer": "abstractavascular necrosis ( avn ) of the scaphoid predominantly occurs in the proximal pole . \n review of the literature revealed only six cases and all are suspect due to the lack of either mri investigation or investigation of bleeding preoperatively . \n we report four new cases and one of them appears to be a real distal pole avn of the scaphoid in the literature .", "id": 755} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhigh resolution transmission electron microscopy and high angle annular dark - field scanning transmission electron microscopy were employed to investigate the microstructure and the epitaxial growth of the structures .\nroom temperature ferroelectric and ferrimagnetic domains of the heterostructures were imaged by piezoresponse force microscopy ( pfm ) and magnetic force microscopy ( mfm ) , respectively .\npfm and mfm investigations proved that the hybrid epitaxial nanostructures show ferroelectric and magnetic order at room temperature .\ndielectric effects occurring after repeated switching of the polarization in large planar capacitors , comprising ferrimagnetic nife2o4 dots embedded in ferroelectric pbzr0.52ti0.48o3 matrix , were studied .\nthese hybrid multiferroic structures with clean and well defined epitaxial interfaces hold promise for reliable investigations of magnetoelectric coupling between the ferrimagnetic / magnetostrictive and ferroelectric / piezoelectric phases .\nthere is no conflict of interest in the present study for any of the authors .", "answer": "epitaxial heterostructures combining ferroelectric ( fe ) and ferromagnetic ( fim ) oxides are a possible route to explore coupling mechanisms between the two independent order parameters , polarization and magnetization of the component phases . \n we report on the fabrication and properties of arrays of hybrid epitaxial nanostructures of fim nife2o4 ( nfo ) and fe pbzr0.52ti0.48o3 or pbzr0.2ti0.8o3 , with large range order and lateral dimensions from 200 nm to 1 micron.methodsthe structures were fabricated by pulsed - laser deposition . \n high resolution transmission electron microscopy and high angle annular dark - field scanning transmission electron microscopy were employed to investigate the microstructure and the epitaxial growth of the structures . \n room temperature ferroelectric and ferrimagnetic domains of the heterostructures were imaged by piezoresponse force microscopy ( pfm ) and magnetic force microscopy ( mfm ) , respectively.resultspfm and mfm investigations proved that the hybrid epitaxial nanostructures show ferroelectric and magnetic order at room temperature . \n dielectric effects occurring after repeated switching of the polarization in large planar capacitors , comprising ferrimagnetic nife2o4 dots embedded in ferroelectric pbzr0.52ti0.48o3 matrix , were studied.conclusionthese hybrid multiferroic structures with clean and well defined epitaxial interfaces hold promise for reliable investigations of magnetoelectric coupling between the ferrimagnetic / magnetostrictive and ferroelectric / piezoelectric phases .", "id": 756} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe immunosuppressive receptor pd-1 and its ligand pd - l1 have been identified by dr .\ntasuku honjo and his colleagues at the kyoto university as factors that \n induce programmed cell death .\nsince the mechanism mediated by pd-1 and its ligand was shown to be important for immune \n suppression and tolerance , it has also been reported to be involved in pathogenetic mechanisms of various diseases . \n\npd-1 and pd - l1 are single - pass transmembrane molecules expressed on the cell surface , which belong to the b7 family . their expression is induced by \n immune - activating stimuli and is understood as a negative feedback mechanism to suppress excessive immune reactions and let immune responses cease .\nwhen the \n receptor pd-1 is bound by its ligand , src homology 2-domain - containing tyrosine phosphatase 2 ( shp-2 ) and shp-1 are recruited to immunoreceptor tyrosine - based \n inhibitory motif and immunoreceptor tyrosine - based switch motif in the intracellular region of pd-1 and suppress antigen receptor signaling mediators .\nthis process results in reduced production of cytokines , such as interferon ( ifn)- and interleukin ( il)-2 , reduced cell \n proliferation and suppressed immune cell activation . in addition to the close involvement in homeostasis of the living body as summarized above , recent studies \n have shown that immunosuppressive factors , pd-1 and pd - l1 , are also involved in immunosuppression in cases of tumors and chronic infections . while generally not \n highly expressed in normal tissues , pd - l1 is expressed at a high rate in tumor tissues in melanoma , lung cancer , colorectal cancer and ovarian cancer , and has \n been demonstrated to be involved in immune evasion by tumors . in patients with renal cell cancer and gastric cancer , \n pd - l1 has been shown to be an important prognostic determinant ; also , the disease progression is faster , and the mortality is higher in patients with tumors \n expressing pd - l1 than in patients without detectable pd - l1 expression [ 51 , 53 ] . in \n addition , pd - l1 expression has also been reported for other tumors including breast cancer , pancreatic cancer and bladder cancer , and pd-1 expression in \n tumor - infiltrating lymphocytes has been confirmed in many types of tumors including melanoma , lung cancer and intrahepatic bile duct cancer .\nthese findings have \n revealed the importance of the pd-1/pd - l1 pathway as an immunosuppression mechanism in a variety of tumors . based on the series of studies on pd-1/pd - l1 in tumor \n diseases , therapeutic means targeting this pathway are being developed .\nspecifically , these new therapeutics are biopharmaceuticals based on anti - pd-1 antibodies , \n anti - pd - l1 antibodies or recombinant proteins that inhibit the pd-1/pd - l1 pathway .\nthese biopharmaceuticals have been reported to show good anti - tumor effects \n regardless of the tumor type and are attracting growing attention as a new , promising class of anti - tumor therapy .\nfully humanized anti - pd-1 and anti - pd - l1 \n antibodies have already been produced and are actively tested as therapeutic agents in clinical studies ( trials ) , with good anti - tumor effects continuing to be \n reported in patients with melanoma , lung cancer , renal cell cancer and some other types of cancer . in melanoma , which has a very poor prognosis , clinical trials \n conducted in japan and the united states have reported not only the suppressed growth of cancer cells , but also complete remission in some cases . on september , \n 2014 , the anti - pd-1 antibody\nwas finally released by ono pharmaceutical as a new anti - tumor therapeutic agent , and it has become a pioneer \n for innovative immune checkpoint inhibitors ( ono pharmaceutical : https://www.opdivo.jp/contents/action/ ) .\nthis immune checkpoint - targeted immunotherapy was \n selected as breakthrough of the year 2013 by the journal science as a global revolutionary technology . currently , merck , roche and other major pharmaceutical \n companies around the world are accelerating their efforts to develop similar antibody - based drugs ; this class of therapeutics is gaining so much momentum and \n attention that the conventional concept of anti - tumor therapy is being overturned .\nthe causative factors of bovine leukemia can be divided \n into viral and non - viral .\nnon - viral bovine leukemia is sporadic and can be subdivided into calf type , thymic type and cutaneous type involving unknown causes .\non \n the other hand , enzootic bovine leukemia , which is caused by blv , accounts for the vast majority of cases of bovine leukemia , and its prevalence continues to \n increase .\nblv infections are latent in the aleukemic ( al ) state , but can emerge as persistent lymphocystosis ( pl ) with non - malignant polyclonal expansion of \n cd5 b - cells that predominantly harbor blv provirus and rarely as malignant b - cell lymphoma in various lymph nodes after long periods of latency \n .\nthe progression of enzootic bovine leukemia is accompanied by marked suppression of cell - mediated immunity [ 8 , 9 , 16 ] , and as the pathogenetic mechanism \n remains unknown , there are no effective vaccines or therapeutic methods available , meaning that affected animals eventually die .\nbovine leukemia was designated as \n a communicable disease obligated to notify under the act on domestic animal infectious diseases control when it was revised in 1997 . in 2015 ,\n2,896 cases of \n bovine leukemia were reported ( of which the largest number of 494 cases occurred in hokkaido ) , representing the disease reported in a greater number than any \n other bovine disease required to monitor by the act ( http://www.maff.go.jp/j/syouan/douei/kansi_densen/kansi_densen.html ) .\nthis number is 29.3-fold the number of \n cases reported in 1998 ( 96 affected animals ) , indicating that the increase has not yet been halted .\nrequests for urgent measures against this disease have been \n voiced very frequently by people practicing veterinary medicine and animal husbandry . however , a large - scale survey conducted by the national institute of animal \n health using specimens collected from 2009 to 2011 showed an approximate blv - positive rate of 35% , demonstrating the difficulty of implementing any project to \n select and replace infected cattle .\ncomparative analyses of blv - infected cattle by clinical condition have suggested that animals with a high viral load and persistent lymphocytosis are at a high \n risk of disease onset , often serving as infection sources , have a high risk of vertical transmission and have increased levels of cd4cd25foxp3 treg cells , showing increased susceptibility \n to opportunistic infections due to transforming growth factor - beta produced by treg cells , which reduces the production of interferon - gamma and tumor necrosis \n factor - alpha by cd4 t cells and impairs cellular immunity mediated mainly by the cytotoxic activity of nk cells [ 28 , 48 ] .\nmoreover , the proliferative ability of lymphocytes in response to blv was also significantly reduced in \n cattle with persistent lymphocytosis , and lymphocytes were found to produce reduced levels of anti - viral cytokines , such as ifn- , il-2 and il-12 [ 13 , 18 ] . therefore , we analyzed the expression of pd-1 and its ligand , pd - l1 .\nresults \n showed that the pd-1 expression in cd4 and cd8 cells and the pd - l1 expression in virus - infected b cells increase as the disease \n progresses .\nfurthermore , pd - l1 expression negatively correlated with the ifn- expression level , an indicator of immunosuppression , while positively correlating \n with leukocyte count , virus titer and provirus level . antibodies to bovine pd-1 and pd - l1 were established , and the results from pd-1 and pd - l1 binding inhibition \n assays confirmed that they activated anti - viral immunity and that the increase in ifn- production positively correlated with the pd-1 expression rate on \n cd4 t cells . and also , recombinant bovine pd - l2 ( pd - l2-ig ) significantly enhanced ifn- production from virus antigens - stimulated pbmcs derived from \n blv - infected cattle .\ninterestingly , the pd - l2-ig - induced ifn- production was further enhanced by treatment with anti - bovine pd-1 antibody .\nthese results indicated that the pd-1/pd - l pathway constitutes a part of the immunosuppressive mechanism in bovine leukemia ( table 2table 2.change of immune inhibitory molecules in the cause of bovine leukemia virus infectionreceptor / liganduninfectedinfected(disease status)referencesalpllymphomapd-1/pd - l1///// lag-3/mhcclass ii////n.d [ 17 , 41]tim-3/gal-9///// ctla-4/cd80 , cd86/n.d/n.d/n.d/n.dn.d n.d : not demonstrated . )\nwe also analyzed immunosuppressive receptors other than the pd-1/pd - l1 pathway , \n such as lymphocyte - activation gene 3 ( lag-3 ) [ 17 , 41 ] , t - cell immunoglobulin and \n mucin domain - containing protein 3 ( tim-3 ) , and cytotoxic t - lymphocyte antigen 4 ( ctla-4 ; cd152 ) expressed in antigen - specific lymphocytes and found that expression levels of lag-3 , tim-3 , ctla-4 and their ligands on lymphocytes \n increased as the disease progressed and anti - viral immunity was activated in binding inhibition assays , as was the case for pd-1 ( table 2 ) .\ncurrently , clinical studies of these drugs are being carried out at the hokkaido university and other institutions .\nalthough there are many diseases in cattle involving immune abnormalities ( impairments ) , the mechanisms underlying these diseases remain unknown .\nour previous \n analyses have shown that immunosuppressive factors , such as pd - l1 , are also involved in immune suppression seen in diseases other than bovine leukemia , namely \n johne s disease and bovine anaplasmosis .\nfurthermore , recent evidence \n suggests that immunosuppressive factors , such as pd-1 , are involved in the reduced immune function in chronic infectious diseases , such as mastitis , bovine \n mycoplasmosis and bovine tuberculosis ( manuscript in preparation ) .\nour laboratory has been working on the development of a blv vaccine for many years .\nit is based \n on a vaccine antigen that was found to be promising in in vitro studies . however , although we tried various procedures , the vaccine did not \n prevent infection or even disease onset despite the fact that effector cells were present in vivo ( data not shown ) .\nresults from the present \n analysis suggested that the virus s immune evasion mechanism for lymphocyte exhaustion might be related to the ineffectiveness of the vaccine .\nfuture measures \n against chronic infectious diseases will require the development of a new , pre - emptive control method that targets this formidable immune evasion mechanism . to \n achieve this goal ,\nresults from more detailed analyses of immune exhaustion in other chronic infections are awaited . for use in humans , several immune \n checkpoint - targeting biopharmaceuticals\nhave been successively developed , including those described above , and they are being actively tested in clinical trials . \n in the future , it is anticipated that they will be applied to veterinary medicine and animal husbandry , including diseases in cattle .", "answer": "recently , dysfunction of antigen - specific t cells is well documented as t - cell exhaustion and has been defined by the loss of effector functions during chronic \n infections and cancer in human . \n the exhausted t cells are characterized phenotypically by the surface expression of immunoinhibitory receptors , such as \n programmed death 1 ( pd-1 ) , lymphocyte activation gene 3 ( lag-3 ) , t - cell immunoglobulin and mucin domain - containing protein 3 ( tim-3 ) and cytotoxic t - lymphocyte \n antigen 4 ( ctla-4 ) . \n however , there is still a fundamental lack of knowledge about the immunoinhibitory receptors in the fields of veterinary medicine . in \n particular , very little is known about mechanism of t cell dysfunction in chronic infection in cattle . \n recent our studies have revealed that immunoinhibitory \n molecules including pd-1/ programmed death - ligand 1 ( pd - l1 ) play critical roles in immune exhaustion and disease progression in case of bovine leukemia virus \n ( blv ) infection , johne s disease and bovine anaplasmosis . \n this review includes some recent data from us .", "id": 757} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nas a service to our authors and readers , this journal provides supporting information supplied by the authors .\nsuch materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset .\ntechnical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .", "answer": "abstracthelically chiral n , n , o , oboron chelated dipyrromethenes showed solutionphase circularly polarized luminescence ( cpl ) in the red region of the visible spectrum ( \n em(max ) from 621 to 663 nm ) . \n the parent dipyrromethene is desymmetrised through o chelation of boron by the 3,5orthophenolic substituents , inducing a helical chirality in the fluorophore . \n the combination of high luminescence dissymmetry factors ( |g \n lum| up to 4.7 103 ) and fluorescence quantum yields ( \n f up to 0.73 ) gave exceptionally efficient circularly polarized red emission from these simple small organic fluorophores , enabling future application in cplbased bioimaging .", "id": 758} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nincidence of ep ranges between 0.25% to 2% of all pregnancies . in 95% of eps ,\nfertilized ovum implants in the tubes , but rarely in other organs like abdomen , ovaries , cervix , spleen , omentum , cessarian section scar , and intramural .\nthe death rate is about 1 per 2000 eps and 15% of all maternal deaths .\nincidence of ep is nearly double in black women who also have a four times greater risk of ep - related mortality than white women .\nthe risk factors for ep include pelvic inflammatory disease , previous tubal surgery , previous tubal pregnancy , progestin contraceptive , assisted reproduction , ovulation induction , induced abortion , salpingitis isthmica nodosa , smoking , and diethyl stilbestrol exposure .\nmost of the tubal pregnancies become symptomatic within 12 weeks , but a small number of them progress beyond this gestation and are diagnosed late .\nproper management of ep needs early diagnosis , resuscitation , timely treatment , and follow - up .\nearly diagnosis of ep is a difficult task but can be possible with the help of quantitative -human chorionic gonadotropin ( -hcg ) level , transvaginal ultrasonography , and laparoscopy .\nknowledge of the risk factors for ep helps in rapid diagnosis and could reduce the need for surgery and suggest actions to improve prognosis .\nhowever , several studies assessing risk factors for ep have been published from developed countries .\nsaudi women have different characteristics , like cultural , religious , sociodemographic , sexual behavior , beliefs , and contraception practices , than those of developed countries and may have different risk factors for ep .\nthe purpose of this study was to highlight the frequency and predisposing factors of ep , and to elucidate the outcome after different treatment modalities in a general hospital .\nthis retrospective descriptive study was conducted at hera general hospital , makkah , saudi arabia , over a duration of 18 months from july 1 , 2009 to december 31 , 2010 .\nthe study subjects included all females in their reproductive age who were admitted at the obstetrics and gynaecology department with suspicion of ep .\ndata were retrieved from the medical record office by exploring the patients files in detail .\npatients files were looked for age ; gravidity ; gestational age ; clinical presenting features ; and ep risk factors , like history of previous abortion , infertility treatment , current use of intrauterine contraceptive device ( iucd ) , history of previous tubal surgery and pelvic surgery , previous ectopic and/or pelvic inflammatory disease .\npeak level of -hcg , transvaginal ultrasonographic findings , mode of treatment , and type of surgical procedure were also retrieved . a woman experiencing several eps during the study period generated multiple case entries , one for each ep episode . in this study , seven women experienced two , and two women experienced three eps .\nthe duration from symptoms onset to admission and admission to definite treatment was also recorded .\nnumerical data were subjected to descriptive analysis , with mean standard deviation ( sd ) .\nthe institutional review board of hera general hospital , makkah , saudi arabia , granted us permission to conduct this study .\nthe institutional review board of hera general hospital , makkah , saudi arabia , granted us permission to conduct this study .\nincidence was 0.58% out of 7654 pregnant women admitted at the department of obstetrics and gynaecology ( 5.8/1000 pregnancies ) .\nthe mean age of the women was 27.9 7 years and only 2 ( 4.5% ) were more than 40 years old .\ntwenty - five ( 56.8% ) were multigravida whereas 21 ( 47.7% ) presented at 7 - 8 weeks of gestation .\nthe range of gestational age was 3 - 9 weeks at presentation . only 24 ( 54.5% ) patients presented within 24 h , 6 patients within 1 - 2 days , and 14 patients presented after 2 days of onset of symptoms of ep .\nthe most common presenting feature was amenorrhea ( 41 , 93.2% ) , followed by abdominal pain ( 39 , 88.6% ) and abdominal tenderness ( 38 , 86% ) .\nfluid in pouch of douglas was found in 21 ( 55.3% ) cases and ectopic mass in 13 ( 34.2% ) cases [ tables 1 and 2 ] .\ndemography and obstetrical history clinical presentation of ectopic pregnancy sixteen ( 36.3% ) females presented with hemoglobin levels of 8 - 10 gm% , followed by 13 ( 29.5% ) with 10 - 12 gm% , 9 ( 20.5% ) with 12 - 14 gm% , and 6 ( 13.6% ) with 8 gm% . twenty - three ( 52.3% ) patients did not receive any blood transfusion during their hospital stay , but 11 patients received one , 5 received two , 3 received three , and 2 patients received 4 units of blood transfusion . out of 44 patients ,\n25 underwent emergency laparotomy whereas the remaining 19 patients were admitted for observation and further diagnosis .\nwhen diagnosis was proved , 12 underwent laparoscopy whereas seven received medical treatment by methotrexate ( mtx ) and it was successful in all cases . on the other hand , salpingectomy was performed in 33 ( 89.1% ) cases followed by salpingostomy in 2 ( 5.4% ) , whereas one case underwent salpingotomy and resection of ectopic mass was performed for the remaining one patient .\npre - operative findings for 37 cases revealed that 35 ( 94.6% ) females had ep in the fallopian tube , whereas one case had within the ovary and one had heterotopic pregnancy , i.e. , combined intra- and extra - uterine .\naverage hospital stay after surgery was 4 days in laparotomy and 2 days in laparoscopy .\neighty percent ( n = 35 ) had some risk factors , whereas previous pelvic surgery was most frequently seen ( 13 , 29.5% ) followed by history of pelvic inflammatory disease ( 10 , 22.7% ) [ table 3 ] .\nthe rate of ep was 1.9% as reported by lozeau and potter in usa , and 1.04% and 1% by bangash and ahmad , and waseem , respectively , in pakistan .\nour study was conducted in a secondary healthcare center , which is why we were not receiving referral cases from the whole of the makkah region , and incidence represented the incidence in hera general hospital rather than the general population of the region .\nmtx treatment of ep was safe and effective for selected patients with unruptured tubal ep , with no major side effects as found by dhar et al .\na paper presented in a conference proceeding highlighted management of advanced ep , i.e. , in bahrain , managements of ep were as follows : laparotomy and salpingectomy ( 84.2% and 5.3% ) , mtx alone ( 5.3% ) and mtx followed by laparotomy and salpingectomy ( 10.5% ) , whereas in qatar it was laparoscopy and salpingectomy ( 77.6% ) , mtx alone ( 19.4% ) , and mtx followed by laparoscopy and salpingectomy ( 3% ) .\nlaparoscopy in qatar and laparotomy in bahrain were the treatment of choice to treat advance ectopic cases .\nlozeau and potter reported a success rate of 88% in a single - dose versus 93% in a multiple - dose regimen of mtx .\nsalpingostomy was concluded as a better option than salpingectomy regarding the future fertility outcome in one study .\nwe tried in our study to increase the clinical knowledge and the degree of suspicion of the physicians to diagnose the ep as early as possible .\nthis will avoid delay in presentation and diagnosis , which is vital to avoid morbidity and mortality in patients with ep .\nafter a review of the literature and our study results , we are in a position to recommend the following steps at three levels i.e. , public , primary healthcare , and specialist center .\naim should be early diagnosis and prompt treatment of ep without unnecessary delay in presentation , diagnosis , and treatment .\nwe should launch a public awareness program about the risk factors to educate all females through electronic media like tv , radio , or newspapers .\nall these patients should register themselves at a specialist hospital for care of their pregnancy where specialist gynecologists and facilities for diagnosis and treatment of ep are available .\ngeneral practitioners working in primary healthcare centers should be educated to have a high index of suspicion for ep . at specialist - level hospitals , all females ( at their child - bearing age ) presenting with hemodynamic instability or pain in the lower abdomen should be admitted and immediate investigations like pregnancy test , -hcg , and ultrasound ( both trans - abdominal and trans - vaginal ) should be ensured even if there is no history of amenorrhea .\nthis study found that previous pelvic surgery , infertility treatment , and pelvic inflammatory disease were the major predisposing factors for ep .\nthe most common site was the fallopian tube and the success rate of mtx was found to be 100% .\nto avoid emergency laparotomy that has its own post - operative complications , timely diagnosis of ep should be encouraged .", "answer": "objectives : the objective was to highlight the frequency , clinical profile , and predisposing factors of ectopic pregnancy ( ep ) in a general hospital.materials and methods : this descriptive study was conducted at the obstetrics and gynaecology department of hera general hospital , makkah , saudi arabia , from july 1 , 2009 to december 29 , 2010 . \n data were collected on chief medical complaints , sociodemographic characteristics , past obstetrics and gynecological history , management done , and outcome of management . \n data were analyzed using microsoft office excel ( version 2007).results : out of total 7564 pregnancies , 44 ( 0.58% ) patients were diagnosed as ep . out of 44 , 22 ( 50% ) \n patients presented within 24 h of onset of symptoms . \n mean age was 28 7 years . \n multigravida were predominant in 25 ( 57% ) , and 21 ( 48% ) had gestational age of 6 - 8 weeks at the time of presentation ; the common presenting features were amenorrhea ( 41 , 93.2% ) , abdominal pain ( 39 , 88.6% ) , and tenderness ( 38 , 86% ) . \n previous pelvic surgery ( 13 , 29.5% ) , infertility treatment ( 11 , 25% ) , and pelvic inflammatory disease ( 10 , 22.7% ) were the common predisposing factors . \n twenty - five ( 57% ) presented with ruptured ep and were operated within 24 h , and the remaining were kept under observation till further diagnosis . after confirming the diagnosis , 12/19 underwent laparoscopy , whereas 7/19 received medical treatment . \n surgery confirmed fallopian tube pregnancies in 35 ( 94.5% ) . \n no mortality was observed.conclusion:previous pelvic surgeries were the major etiological factor for ep . \n other factors were infertility treatment and pelvic inflammatory disease . \n the most common site of ep was fallopian tubes .", "id": 759} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nphysical activity during preschool age has significant effects on physical , social and psychological health of children .\nfundamental movement skills ( fms ) including locomotor ( e.g. run , gallop , hop , leap , horizontal jump and slid ) , object control ( e.g. catch , kick , overhand throw and dribble ) and body management ( e.g. balance , climb and forward roll ) provide a base for more advanced physical skills . fms develop during early childhood and are essential for complex activities at adulthood .\nsome studies have shown that the level of locomotor skills of children is positively correlated with the levels of participation in physical activities at adulthood[34 ] .\nd'hondt et al reported that the levels of gross motor skills in obese children are lower than the levels of these skills in normal - weight children .\ntherefore it seems likely that more proficient children in fms are more physically active , have more self confidence , are less obese and would be healthier in their adulthood .\nfms would not be developed naturally as a result of growth and maturation in all children .\nit has been suggested that the optimal ages for fms learning are between 2 to 7 years[2 , 6 ] .\nbrian w et al have recommended that physical activity promotional programs for preschool children should be on base of children 's natural activities such as being spontaneous and intermittent . also preschool children activities should be enjoyable and contain gross motor plays and locomotor activities .\ntherefore , it seems that an effective physical activity program for preschool children needs to be developmentally appropriate for children in the listed age range .\nfurthermore , physical , emotional and psychosocial needs of children should be considered in development of appropriate physical activity program for these children . ideally physical activity programs in nursery schools\nalso a well developed training course for these instructors is essential in efficient teaching of movement skills to children in nursery schools[1 , 9 ] .\nin addition to the role of fms in long - term health , fms play a cardinal role in physical development of preschool children . to our knowledge\nthere is no national curriculum for preschool children physical activity education in iranian nursery schools .\nthe objectives of this study were a ) to develop a physical activity program for nursery schools in iran , and b ) to evaluate the effects of this program on improvement of fundamental movement skills of preschool children in selected nursery schools in iran .\nthis quasi - experimental study evaluated the effect of a 10 weeks physical activity program on fundamental movement skills levels of nursery children in iran .\nthe participants were 147 children with age range between 4 to 6 years that were selected by convenience sampling .\nchildren selected form five available nursery schools in five different cities in iran . a manual for nursery physical activity instructors was developed by a panel of 20 experts in different related fields in iran including sports medicine specialist , pediatrician , expert nursery teachers , psychologist , nutritionist , physical education specialist , phd in sports physiology , and phd in movement and behavior .\nthis manual contained two parts ; a ) instructions for nursery physical activity instructors about goals and structure of the program , and materials on children 's growth and development , children 's nutrition , physical education , psychology of children , and health and safety , b ) twenty four sections which cover different lessens containing physical activity and games aimed at developing locomotor and object control skills of children aged 4 to 6 years .\nsome sections of this package were developed based on the iranian traditional games and plays that were appropriate for preschool ages .\nfive nursery schools were selected in five different cities ( tehran , isfahan , shahrood , neishaboor and gorgan ) and volunteer nursery teachers of these nursery schools were enrolled in an educational course .\nthis one week course was designed to train nursery physical activity instructors to be able to physically train children in nursery based on our designed physical activity program .\nthe aim of this short - term educational program was to ensure that all physical activity instructors are alert to their duties about implementing of the developed physical activity manual .\nalso physical activity instructors were educated to test children using the test of gross motor development - edition 2 ( tgmd-2 ) before and after intervention .\npersian version of this test has been employed by akbari h , et al . and bakhtiari s , et al . in iran[9 ,\nthe levels of gross motor development of all subjects were measured before intervention and after 10 weeks physical activity program employing tgmd-2 .\ntgmd-2 is a valid and reliable ( test - retest reliability = 0.88 - 0.96 ) criterion - referenced instrument designed to assess gross motor development among children .\neach subtest consists of 6 locomotor items ( run , hop , gallop , leap , horizontal jump , and slide ) , and 6 object control items ( throw , catch , kick , strike , dribble , and roll ) .\nsubtest raw score was defined by sum of 6 items of each subtests of locomotor or object control ( scored between 0 - 48 ) .\nstandard scores of each subtest ( scored between 0 - 20 ) and also gross motor quotient were calculated in accordance with tgmd-2 manual .\n( gmq ) for each subject was reported as very superior ( gmq > 130 ) , superior ( gmq = 121130 ) , above average ( gmq = 111120 ) , average ( gmq = 90110 ) , below average ( gmq = 8089 ) , poor ( gmq = 7079 ) , and very poor ( gmq < 70 ) according to the suggestions of the tgmd-2 manual . according to developed physical activity manual\n, physical activity program was conducted 5 days a week for 10 weeks by trained nursery physical activity instructors .\npaired - samples t test was used to determine whether there were significant differences between the levels of locomotor and object control of participants before and after intervention .\nindependent samples t - test was used to compare differences between boys and girls on variables .\nin this quasi - experimental study 147 children with mean ( sd ) age of 4.95 ( 0.8 ) ( range 3 - 6 ) year from five nursery schools in 5 cities in iran were included .\nof all subjects 49% ( 72 ) were girls and 51% ( 75 ) were boys .\nthe base line and post intervention tgmd-2 scores of subjects are presented in tables 1 and 2 . in the baseline\n, there were no statistically significant differences between the locomotor and object control raw scores of boys and girls ( p=0.49 and p=0.9 ) respectively . \n \nbase line and post intervention tgmd-2 scores of all subjects sd : standard deviation means ( sd ) of base line and after intervention tgmd-2 raw scores of all subjects by age and gender sd : standard deviation after intervention , differences between the locomotor raw scores of boys and girls were not statistically significant ( p=0.5 ) .\nhowever , there was a statistically significant difference between boys and girls in the object control raw scores ( p=0.048 ) .\nthe gmq of all subjects which is the most reliable score of tgmd-2 was statistically significantly increased after 10 weeks of intervention .\nboth subtests of tgmd-2 including locomotor raw score and object control raw score in both genders were statistically significantly increased after 10 weeks of intervention ( table 1 ) .\ndescriptive rating of gmq for subjects before and after intervention is shown in table 3 . before intervention only 11.5% of all subjects were rated superior / very superior in gmq scores ( i.e. gmq > 120 ) , however this rate increased to 49.7% of all subjects after 10 weeks of intervention . before the intervention ,\n26.6% of all subjects were rated as poor / very poor , this rate decreased to 2% of subjects after 10 weeks intervention .\nage equivalents of subjects on the locomotor and object control subtests before and after intervention are shown in table 4\n. age equivalents or developmental age defined as developmental level or age that corresponds to a raw score made by an individual . \n \ndescriptive rating of the gross motor quotient of all subjects before and after intervention age equivalents for locomotor and object control raw scores according to age groups of all subjects before and after intervention\nthe main finding of this study was that the developed physical activity intervention program that was focused on gross motor skills development had a significant positive effect on proficiency in fundamental movement skills in preschool children from selected nursery schools in five cities in iran .\ndifferences in tgmd-2 results before and after the intervention were significant in locomotor , object control , sum of standard cores and gross motor quotient in all subjects . to our knowledge\nthere has been no published data on the levels of physical activity of iranian preschool children .\nhowever , base line tgmd-2 subtests scores of our subjects in this study were in the range of reported data from the united states ( table 5 ) . \n \ncomparison of tgmd-2 standard scores of subjects in this study with reported data from the united states , mean ( sd ) sd : standard deviation our data suggested that a supervised physical activity program could increase these scores to be better than normative reported data .\nthere was no significant difference in the base line mean of the locomotor and object control raw scores between girls and boys ( 30 vs 29.5 ) and ( 24.8 vs 26 ) , respectively .\nhowever after the intervention the mean of both object control raw scores ( p=0.048 ) and object control standard scores ( p=0.02 ) in girls were higher than these scores in boys .\ncliff et al have reported that locomotor raw score in preschool children was higher in girls compared with boys but there was no significant difference between girls and boys in the object control raw score . in this study ,\nbase line means of standard scores of the locomotor ( 9.3 vs 8.9 ) , object control ( 9.1 vs 8.1 ) and gmq ( 95.5 vs 91.2 ) were not significantly different between girls and boys .\nin contrast cliff et al have reported significant differences between girls and boys in the mean of locomotor standard scores ( 9.9 vs 7.9 ) , object control standard scores ( 10.1 vs 8.6 ) and gmq ( 99.7 vs 88.2 ) .\none study has reported that locomotor skills proficiency is higher in girls and in contrast boys are more proficient in object control skills .\nsome studies have suggested that the levels of moderate and vigorous physical activities in children with better motor performance are significantly higher than the levels of these activities in children with less developed skills[4 , 19 ] .\ntherefore , conduction of a physical activity program such as the program used in this study may help children to improve their fms which may help to have a higher physical activity in their future .\nfirst , same person conducted both training sessions and outcomes measurement in each nursery school .\nfurthermore , to our knowledge there was no normative data of tgmd-2 for iranian children to be used for comparison with our data .\nfurther studies are needed to evaluate the long - term effects of physical activity intervention on fms in iran .\nit seems that our developed physical activity program conducted by trained nursery physical activity instructors could be an effective and practical way of improving gross motor skills of preschool children in short term in iran .\nconduction of this program in nursery schools could indirectly help with increasing health levels and levels of physical activities in the society .\nwe recommend using of this kind of physical activity programs in all nursery schools in iran and similar counties .", "answer": "objectivethe objectives of this study were a ) to develop a physical activity program for nursery schools , and b ) to evaluate the effects of this program on fundamental movement skills of preschool age children in iran.methodsin this quasi - experimental study 147 children from five nursery schools in five different cities in iran were enrolled . \n a physical activity program was developed for nursery children . \n trained nursery physical activity instructors conducted the program for 10 weeks for all subjects . \n the levels of gross motor development of all subjects were measured before intervention and after 10 weeks physical activity program employing the test of gross motor development - edition 2 ( tgmd-2).findingsthe participants in this study had a mean ( sd ) age of 4.95 ( 0.83 ) years . at the end of the study , scores of subjects at all components of tgmd-2 ( including locomotor , object control , sum of standard scores and gross motor quotient ) \n were significantly improved compared to the baseline scores ( p<0.001 ) . \n based on descriptive rating of the \" gross motor quotient \" in the base line , 11.5% of subjects were superior / very superior ( gmq > 120 ) and after 10 weeks intervention this rate was increased to 49.7% of all subjects.conclusionit seems that the developed physical activity program conducted by trained nursery physical activity instructors could be an effective and practical way of increasing levels of fundamental movement skills of preschool children in iran .", "id": 760} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfirst described in 1910 , purtscher s retinopathy is seen in severely traumatized patients and is characterized by sudden visual loss ( purtscher 1912 ) .\nthe characteristic ophthalmoscopic findings are multiple areas scattered throughout the posterior pole of superficial retinal whitening , which appear as focal areas of retinal arteriolar occlusion on fluoresceinangiography ( grass 1997 ) .\nsimilar clinical findings have been reported in association with childbirth ( blodi et al 1990 ; shaikh et al 2003 ) , and have been termed purtschers - like retinopathy . the visual prognosis in purtschers - like retinopathy after childbirth is guarded , and to date , there is no definitive treatment .\nhowever , there are encouraging reports of visual recovery in patients with purtscher s retinopathy receiving high dose intravenous corticosteroid therapy ( atabay et al 2003 ) .\nwe report a patient with purtschers - like retinopathy following childbirth who received a sub - tenon s capsule injection of triamcinolone with subsequent increase in visual acuity and decrease in retinal swelling .\nten days after an emergent caesarian section for severe preeclampsia , rh immunization , and fetal anemia , a 24 year - old primigravida primiparus patient presented with complaints of decreased vision in both eyes , right greater than left . there were no other systemic abnormalities such as elevated liver enzymes , low platelets or other hematologic abnormalities .\ndilated fundus examination revealed bilateral purtschers - like retinopathy ( figures 1a , 1b ) , with widespread areas of macular ischemia and edema , as confirmed by optical coherence tomography ( figures 2a , 2b ) .\nof note are the superficial areas of high intensity signal , indicative of retinal ischemia .\nthe central thickness in the right eye was 272 microns , and in the left 239 microns .\na sub - tenon s injection of 0.5 cc of triamcinolone ( 40 mg / cc ) was given in the right eye on day 15 after delivery .\nat one week following the injection , her visual acuity was unchanged and her intraocular pressure was normal .\nshe noted a marked improvement in the vision in her right eye . on examination a her acuity\nhad improved to 20/60 in the right eye and 20/20 in the left , with normal intraocular pressures .\nher fundus examination showed marked improvement , with most of the superficial ischemic areas resolving .\nrepeat optical coherence tomography in both eyes ( figures 3a , 3b ) demonstrated a reduction in the edema of the right eye by 30% from baseline , whereas the left , untreated eye showed a reduction in swelling of 14% .\nher visual acuity remained 20/60 in the right eye and 20/20 in the left eye .\nnearly a century ago otmar purtscher described a case of visual loss in a severely traumatized patient whose exam showed multiple superficial retinal hemorrhages and white patches throughout the posterior pole . since that time , similar findings have been associated with other conditions including compressive chest injuries , acute pancreatitis , fat embolism , retro - bulbar anesthesia , connective tissue diseases ( grass 1997 ) , and childbirth ( blodi et al 1990 ; shaikh et al 2003 ) .\nthe pathogenesis of purtschers - like retinopathy post - partum is unknown , but may be related to arteriolar obstruction by complement induced leukoemboli produced during parturition ( blodi et al 1990 ) .\nsimilar clinical findings have been reported in the setting of amniotic fluid embolism . however , in the absence of a patent foramen ovale or pulmonary arteriovenous - shunts , it is unlikely that amniotic emboli are the direct cause of the observed retinal arteriolar obstructions .\nother investigators have theorized that subclinical amniotic fluid emboli may activate complement and induce granulocyte microemboli , which could occur on both sides of the pulmonary capillary bed .\nthe visual recovery of postpartum patients with purtschers - like retinopathy is varied ( blodi et al 1990 ; shaikh et al 2003 ) . of the four patients described by blodi , three enjoyed significant improvement in central acuity ,\nanother case of purtscher - like retinopathy has been described in a patient with hellp syndrome during antepartum .\ngenerally purtscher - like retinopathy has a favorable prognosis but this case resulted in permanent loss of vision ( stewart et al 2007 ) .\ncurrently , there is no definitive treatment for postpartum purtschers - like retinopathy . in vivo\n, corticosteroids have been shown efficacious in inhibiting complement - induced granulocyte aggregation ( hammerschimidt et al 1979 ) .\nclinically , there are two reports of visual recovery after high dose , intravenous corticosteroid therapy in post - traumatic patients ( atabay et al 1993 ) .\nthe case presented here is unique in that the patient had bilateral , asymmetric purtschers - like retinopathy post - partum , with quantitative oct improvement following unilateral local steroid therapy .", "answer": "sub - tenon s injection of triamcinolone was performed in the right eye of a patient with bilateral purtschers - like retinopathy after childbirth . \n the response of macular edema to local triamcinolone was investigated with optical coherence tomography . \n five weeks following the injection , optical coherence tomography improvement was seen following unilateral sub - tenon s triamcinolone injection .", "id": 761} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe retrorectal space is an uncommon area where tumors occur and these include primary tumors of neurogenic , osteogenic , and congenital origin ; in addition to metastatic and inflammatory processes .\ncongenital lesions include chordomas ( remnants of notochord ) , teratomas , anterior sacral meningoceles , and developmental cysts ( dermoid , epidermoid , enteric duplication , and tailgut cysts ( tgcs ) ) .\ntgcs , also known as retrorectal cystic hamartomas , are a rare congenital lesion thought to arise from the remnants of the embryonic postanal gut .\nhjermstad and helwig were the first to publish their findings in 1988 , and since then there have been no large case series reported . from review of the literature done by killingsworth and gadacz (\nkeyword = tailgut cyst or retrorectal cystic hamartoma , limits = english ) , there have been 43 cases with confirmed diagnosis of tgc since their report .\na 15-year - old girl presented with the complaints of lower abdominal pain and constipation occasionally .\nhowever , on per rectal examination , there was a mass bulging from the posterior rectal wall , firm , and non - tender , with regular surface and smooth mobile rectal mucosa over it .\nan ultrasonogram ( abdominal ) revealed a large cystic lesion present in the left lower abdomen and the left ovary could not be seen separately .\nthe patient then underwent a contrast - enhanced computed tomography ( cect ) of the abdomen and pelvis which revealed a well - defined 12 13 9 cm multiseptated lesion in the presacral space which was pushing the rectum laterally and urinary bladder superiorly and abutting the sacrum and coccyx posteriorly [ figure 1a and b ] .\nthe lesion was showing peripheral and septal calcification , few hyperdense nonehancing areas and few ossified fragments within it .\na provisional diagnosis of mature cystic teratoma was made and the patient underwent exploratory laparotomy wherein a large tubular tense cystic mass resembling fluid - filled intestinal loop filled with thick mucoid material was present in the presacral space [ figure 2 ] .\nthe two ends of the tube were merging at the coccyx . the mass was displacing the sigmoid colon and rectum laterally and urinary bladder anteriorly . en masse removal was done .\ncect abdomen showing multiseptated pre sacral mass compressing the rectum and displacing bladder superiorly intraoperative picture showing a tubular fluid - filled structure displacing the bowel loops the patient had an uneventful postoperative recovery\n. the histopathological examination revealed it to be a retrorectal cystic hamartoma with areas of intestinal ( large and small ) and gastric epithelium .\na solitary solid area within it had intestinal lining with area of squamous epithelial nests , haphazardly arranged muscle bundles , nerve bundles , and serous acini with few cystic spaces [ figure 3a c ] .\nhistopathological image showing ( a ) gastric mucosa , ( b ) ectopic gastrointestinal gland and ( c ) ectopic pancreatic epithelium\nthe retrorectal space is a potential space developed when a mass displaces the rectum anteriorly .\nthe pelvic peritoneal reflection forms the superior border , and the levator ani and coccygeus muscles form the inferior border .\nthe differential diagnosis of masses within this space is broad and includes primary tumors of neurogenic , osteogenic , and congenital origin ; in addition to metastatic and inflammatory processes .\ncongenital lesions include chordomas , teratomas , anterior sacral meningoceles , and developmental cysts ( dermoid , epidermoid , enteric duplication , and tgcs ) . excluding inflammatory lesions , developmental cysts are the most common masses in the retrorectal space .\n. only one case of a retrorectal cystic hamartoma occurred in a 2-year - old child and very few cases have been reported in teen aged girls , as in our case .\nthe differential diagnosis for a retrorectal mass can be narrowed using a combination of diagnostic tools to reach a preoperative diagnosis of a developmental cyst . due to their location\n, almost all retrorectal tumors will be palpable on rectal examination , and developmental cysts will manifest as extrinsic masses .\nct and magnetic resonance imaging ( mri ) are useful imaging modalities that help in making a preoperative diagnosis . however , the definitive diagnosis and treatment is through complete surgical excision and pathological examination of the specimen .\npreoperative biopsy should not be attempted ( unless the mass is surgically unresectable at presentation ) due to risk of spreading dysplastic cells through weakened cyst walls .\nin addition , tissue obtained from biopsy is often not extensive enough to show all the histology features necessary for diagnosis .\ndermoid and epidermoid cysts are both lined with stratified squamous epithelium ; however , only dermoid cysts contain dermal appendages ( hair follicles , sweat glands , and tooth buds ) .\nepidermoid cysts are formed from inclusion of epidermal elements at the time of neural groove closure in the meninges .\nrectal duplication cysts are lined by typical gastrointestinal epithelium ( often with crypts , villi , and glands ) and are surrounded by two well - formed layers of smooth muscle with nerve plexuses .\ntgcs , or retrorectal cystic hamartomas , are predominantly multicystic and can contain a variety of epithelia between cysts or even within the same cyst .\nepithelial types include stratified squamous , transitional , mucinous or ciliated columnar , and cuboidal mucus secreting .\nin contrast to enteric duplication cysts , tgcs have disorganized smooth muscle fibers within the cyst wall and do not contain neural plexus .\nretrorectal hamartoma or tgc should be considered as a possible differential in any case of perirectal cyst , irrespective of age and gender .", "answer": "the retrorectal space is an uncommon seat for neoplastic masses . \n retrorectal hamartoma or tailgut cyst ( tgc ) is an uncommon developmental cystic lesion occurring in this space which mostly occurs in middle - aged females . \n we recently cared for a 16-year - old girl who presented with vague lower abdominal pain and occasional constipation . \n per rectal examination revealed an extraluminal mass bulging from posterior rectal wall . \n preoperative radiological investigations revealed by suggested it to be a mature cystic teratoma . \n the patient underwent exploratory laprotomy with en masse excision of the cyst . \n histopathological examination of the specimen showed it to be a tgc . \n this case highlights the possibility of a tgc as a differential for retrorectal cystic lesions and the need to completely excise them given the possibility of future malignant transformation .", "id": 762} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nblunt traumatic infrarenal aortic injuries are rare , with a few case reports in the literature .\na more common occurrence is an intimal flap which may form after blunt injury to the aorta , and most of these will resolve with anticoagulation alone [ 1 , 2 ] .\nblunt aortic injury which initially presents as an intimal flap ( grade i ) may progress and evolve into an intramural hematoma ( grade ii ) or a pseudoaneurysm ( grade iii ) .\naortic intimal flap progressing to dissection or pseudoaneurysm is an occurrence identified in 2% or less of the patients , and the majority of these occur in the thoracic aorta [ 1 , 2 ] .\nthis article presents the case of a young woman found to have an intimal flap in the infrarenal abdominal aorta after a car accident , and the injury progressed to a pseudoaneurysm over 3 months .\na 47-year - old woman with a history of hypertension and smoking was involved in a high - speed motor vehicle accident and presented to the emergency department with back pain .\ncomputed tomographic ( ct ) scans were obtained of her abdomen and pelvis . on a single image from the abdominal scan ,\nwhat appeared to be either an intimal flap or a small amount of contrast extravasation outside of the infrarenal aorta could be seen .\nher care providers had differing opinions as to what was being seen on the image .\nsince the abnormality was only seen on a single image , the exact etiology could not be delineated ( fig .\nthe patient was observed in the hospital overnight , had minimal complaints the next day , and was discharged on aspirin . \n\nfigure 1:initial ct scan shows enhancing vascular abnormality on the right side of the aorta , shown by the black arrow .\ninitial ct scan shows enhancing vascular abnormality on the right side of the aorta , shown by the black arrow .\na follow - up ct scan was obtained 3 months later . at the location of the previous aortic abnormality\n, there was a 3 1 cm pseudoaneurysm that had formed and could now be clearly seen ( figs 2 and 3 ) .\nfigure 2:pseudoaneurysm now clearly seen 3 months later . \n figure 3:black arrow pointing to pseudoaneurysm with enhancing flow outside of the aortic lumen .\noperative repair was recommended , but the patient s aorta measured only 18 mm at the aortic bifurcation and was too small for even the smallest endovascular stent graft available at our institution .\ntherefore , an open replacement of her infrarenal aorta was performed using a dacron 22 mm graft . in the operating room ,\nafter the aorta was clamped and opened , a 4 mm tear in the intima had formed a mature channel into the pseudoaneurysm .\nthe patient recovered very well and was discharged from the hospital without complications . at her\n2-year follow - up , she was in good health and had no further problems , but continues to smoke .\nblunt abdominal aortic trauma occurs in only 0.040.1% of all nonpenetrating traumas [ 3 , 4 ] . and\nthe vast majority of these ( 92% ) are associated with multiple other injuries [ 3 , 5 ] .\nour patient had no other injuries , and there was no retroperitoneal hematoma or other signs of vascular injury in the area , as is usually seen on ct when the aorta is injured [ 35 ] .\nthe lack of other radiographic traumatic findings added to the initial confusion as to whether there was a true injury to the aorta , or if the single image was showing artifact or an enlarged vertebral vessel .\nsince the majority of intimal flaps heal with anticoagulation alone ( 55% ) or remain stable ( 40% ) , a conservative plan including daily aspirin and re - imaging in 3 months was chosen . when repeat imaging showed a 3 cm pseudoaneurysm , operative repair was necessary .\nendovascular repair was initially chosen for this case , but after measuring the patient s aorta , femoral vessels and the degree of taper at the bifurcation , there was not an appropriate endovascular prosthesis available in such a small size .\nonly one study has compared conventional open repair with endovascular repair for blunt injuries of the abdominal aorta and found similar results in both groups .\nendovascular repair is generally favored since the injuries tend to be focal and discrete , making them quite amenable to a short graft .\nfurther , the patients usually have other significant injuries that would complicate a long , and potentially morbid , open operation on the aorta .\nalthough all blunt infrarenal aortic injuries are unusual , most of them consist of intimal flaps or dissections [ 3 , 58 ] .\na post - traumatic pseudoaneurysm , as this patient had , is even more unusual after blunt trauma .\none prior publication did document the delayed occurrence of a post - traumatic infrarenal aortic pseudoaneurysm that was diagnosed 3 years after injury .\nendovascular repair for pseudoaneurysms must include post - procedure angiography to document no evidence of a type i or type ii endoleak , which could allow filling of the aneurysm sac and later rupture .\nthis case report highlights the need for delayed imaging for even minor intimal flaps or small aortic injuries after trauma , since progression does occur .\nwhile the vast majority of these injuries improve over time or remain stable , a small percentage will worsen and require intervention .", "answer": "blunt traumatic infrarenal aortic injuries are unusual , and the formation of a delayed pseudoaneurysm of the aorta is even more rare . in this report \n , a young woman developed a small intimal flap of the infrarenal aorta after a motor vehicle accident which progressed into a 3 cm pseudoaneurysm after 3 months . \n operative repair was successful and the patient recovered . \n this case illustrates the importance of repeat imaging of small blunt aortic injuries since progression can occur .", "id": 763} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe assembled snp array data from 29,589 unrelated people and 222 nuclear families genotyped at 490,000910,000 snps from the candidate gene association resource ( care ) , studies at the children s hospital of philadelphia ( chop ) , the african american breast cancer consortium , the african american prostate cancer consortium and the african american lung cancer consortium . to build a recombination map , we used hapmix to localize candidate crossover positions , and implemented a markov chain monte carlo ( mcmc ) that used the probability distributions for the positions of the filtered crossovers to infer recombination rates for each of 1.3 million inter - snp intervals .\nwe also implemented a second mcmc that models each individual s set of crossovers as a mixture of a shared ( s ) map similar to the european decode map and an african - enriched ( ae ) map , and then assigns each individual an ae phenotype corresponding to the proportion of their newly detected crossovers assigned to the ae map .\nwe imputed genotypes at up to three million hapmap2 snps using mach , and then tested each of these snps for association with the ae phenotype and other recombination - related phenotypes .\nwe identified 2,454 candidate african - enriched hotspots with increased recombination rates in the yri vs. ceu maps , and in the ae vs. s maps , and searched for motifs enriched at these loci , thus identifying a degenerate 17-bp motif . to study the structure of prdm9 ,\nwe measured the length of the prdm9 zinc finger array and genotyped rs6889665 in yri , ceu and the care nuclear families ; we also carried out imputation based on 1000 genomes project short read data to infer the alleles individuals carry , among 29 previously characterized in a sequencing study of prdm9 .", "answer": "recombination , together with mutation , is the ultimate source of genetic variation in populations . \n we leverage the recent mixture of people of african and european ancestry in the americas to build a genetic map measuring the probability of crossing - over at each position in the genome , based on about 2.1 million crossovers in 30,000 unrelated african americans . at intervals of more than three megabases \n it is nearly identical to a map built in europeans . at finer scales it differs significantly , and we identify about 2,500 recombination hotspots that are active in people of west african ancestry but nearly inactive in europeans . \n the probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at prdm9 ( p<10245 ) . \n we identify a 17 base pair dna sequence motif that is enriched in these hotspots , and is an excellent match to the predicted binding target of african - enriched alleles of prdm9 .", "id": 764} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbariatric surgery has become an effective treatment for obesity , also reducing the onset of type 2 diabetes mellitus ( t2 dm ) as well as inducing remission and reducing cardiovascular mortality and mortality in general [ 3 , 4 ] . \nobesity is a chronic condition characterized by elevated inflammatory markers [ 57 ] and is associated with nonalcoholic fatty liver disease ( nafld ) [ 8 , 9 ] .\nserum gamma - glutamyltransferase ( ggt ) and alanine aminotransferase ( alt ) are markers of nafld and of liver fat content [ 10 , 11 ] .\nincreased platelet counts have been observed in conditions with chronic inflammation as well as in obesity , probably due to secondary thrombocytosis [ 1214 ] . in more advanced stages of nafld , with portal hypertension and splenomegaly ,\nthere is a linear association between decreased platelet counts and increased fibrosis in the histopathology of liver biopsies , which may indicate that platelet counts might be an important biomarker of the degree of fibrosis in nafld patients .\nplatelet count is a simple , easy to perform , cost - effective , and accurate surrogate marker for predicting fibrosis severity in nafld patients .\nbariatric surgery improves steatosis and fibrosis in patients with morbid obesity nafld , and adjustable gastric banding in a previous study has been related to a nonsignificant trend of lowered platelet counts .\nregarding rygbp , one study reports a significant reduction in platelet counts 1 year after surgery .\ndata after longer periods of followup , after rygbp as well as bpd - ds surgeries , are lacking .\nthe aim of this study was to assess changes , if any , in morbidly obese patients treated with bpd - ds and rygbp , from baseline , that is , before surgery , to followups 1 year and 3 years after surgery , with regard to platelet counts and serum concentrations of ggt and alt .\nten morbidly obese patients who had undergone bpd - ds surgery ( five men and five women ) , all caucasians , free from established diabetes , were recruited from the outpatient clinic of obesity care , uppsala university hospital , uppsala , sweden .\ndata from the bpd - ds group were compared to that of a morbidly obese group ( n = 21 ; three men and eighteen women ) , all free from established diabetes and had undergone rygbp .\npatients were investigated preoperatively ( baseline ) and then 1 year ( 1st followup ) and 3 years ( 2nd followup ) after bpd - ds and rygbp , respectively .\nroux - en - y gastric bypass is a procedure that combines restriction and malabsorption .\nit is considered by many to be the gold standard because of its high level of effectiveness and its durability .\nmore extreme malabsorption accompanies biliopancreatic diversion procedures , commonly performed with a duodenal switch in which a short , distal and common channel length of small intestine severely limits caloric absorption , which induces a greater weight loss than rygbp does .\na very high bmi indicated that bpd - ds procedure was performed instead of rygbp at our clinic [ 19 , 20 ] .\nall participants underwent physical examination and blood tests for platelet count , ggt , and alt preoperatively ( baseline ) and at the 1st and 2nd followups .\nblood samples were collected from each patient ( following an overnight fast ) and were analyzed using routine tests at the department of clinical chemistry at uppsala university hospital [ 19 , 20 ] . weight ( kg ) and height ( m ) were measured on standardized calibrated scales , and bmi ( kg / m ) was calculated . \ntests were two tailed , and a p value < 0.05 was considered significant .\npatient clinical characteristics at baseline , that is , before rygbp and bpd - ds surgeries , are shown in table 1 .\nthere were no statistically significant intergroup differences in platelet counts or plasma concentrations of ggt and alt .\nmean weight and bmi were , as expected , higher in the bpd - ds group , selecting the patients for this procedure , and age was lower .\nbmi decreased by 43% in the bpd - ds group from 53.5 kg / m at baseline to 30.7 kg / m at 1st followup ( p < 0.001 ) and was unchanged between the 1st and 2nd followups ( 30.2 kg / m , p < 0.001 ) , as shown in figure 1(a ) . in the rygbp group ,\nbmi was reduced by 30% from 42.3 kg / m at baseline to 29.7 kg / m at the 1st followup ( p < 0.001 ) but was 32.1 kg / m at the 2nd followup ( p < 0.001 ) , implying a 6% gain ( gain over the baseline bmi ) between the 1st and 2nd followups ( p < 0.001 ) .\nplatelet counts were reduced by 22% in the bpd - ds group from 308 10/l at baseline to 240 10/l at the 1st followup ( p < 0.001 ) and were unchanged at the 2nd followup ( 244 10/l , p < 0.001 ) , as shown in figure 1(b ) . in the rygbp group , platelet counts were reduced by 10% from 297 10/l at baseline to 266 10/l at the 1st followup ( p = 0.012 ) but were 292 10/l at the 2nd followup ( p = 0.687 ) , implying a 9% increase between the 1st and 2nd followups ( p = 0.024 ) .\nkatal / l at the 1st followup ( p = 0.01 ) and was 0.32 \nkatal / l at the 2nd followup ( p < 0.001 ) , but this further decrease was not significant ( p = 0.867 ) , as shown in figure 1(c ) . in the rygbp group , ggt\nkatal / l at the 1st followup ( p < 0.001 ) , with no further alteration at the 2nd followup ( 0.31 katal / l , p < 0.001 ) .\nkatal / l at the 1st followup ( p = 0.004 ) and was unchanged at the 2nd followup ( 0.41 katal / l , p = 0.004 ) . in the rygbp group ,\nkatal / l at the 2nd followup ( p < 0.001 ) , implying a further decrease by 16% between the 1st and 2nd followups ( p = 0.02 ) .\nthe main findings in this study were that liver enzymes , ggt and alt , markedly decreased over time after both rygbp and bpd - ds surgeries , but platelet counts only decreased significantly after bpd - ds .\nthe alteration in platelet counts showed a somewhat different pattern after rygbp , with a reduction at the 1st followup but no significant change at the 2nd followup .\nit might be speculated that the sustained reduction in platelet counts may indicate a long - term improvement in the inflammation of the liver and a more pronounced decrease of liver - fat - content - related inflammation in obese patients treated by bpd - ds compared to rygbp .\nplatelets vary daily and are depending on a variety of issues such as ethnicity , age , and gender .\nbuckley et al . have showed in their analysis of serial platelet counts from 3,789 subjects that the repeatability of the platelet count is very high .\nobesity is an inflammatory condition [ 23 , 24 ] and a major risk factor for the development of nafld and liver disease . in obese patients ,\nultrasonographic examinations as well as liver biopsies have revealed that nafld is very common . as it is difficult to perform biopsies in all nafld patients ,\nit has been reported that a lowered ggt may best predict improvements in inflammation and fibrosis in the hepatocytes in nafld , which are two major prognostic features in this condition , whereas changes in aminotransferase concentrations did not predict change in steatosis .\nfurthermore , increased numbers of platelets are observed in conditions with low - grade inflammation , such as obesity , although the platelet counts are within normal ranges .\noverweight , obese , and morbidly obese females have significantly elevated platelet counts compared with normal - weight females and male subgroups .\nthe gender difference in platelets might be due to the higher body fat mass in females .\nhigher platelet counts are associated with more adverse clinical outcomes in patients with myocardial infarction and stroke .\nobesity is also associated with platelet dysfunction , increased adhesiveness , and activation [ 2628 ] . in more severe states of nafld with fibrosis , a consumption of thrombocytes are observed . in a recent study ,\nyoneda et al . used liver biopsies to evaluate the clinical usefulness of measuring platelet counts for predicting the severity of liver fibrosis in 1,048 patients with nafld .\nour data show a sustained reduction in platelet counts over time after bpd - ds , probably induced by a more pronounced weight loss than after rygbp and possibly a more pronounced decrease of liver inflammation .\none year after rygbp , a significant reduction in platelet counts was observed , which is in accordance with 1 year data from dallal et al . , but the reduction was not sustained at the 2nd followup , 3 years after surgery .\nthere are several limitations in the present study such as the small number of patients and the lack of a morbidly obese control group followedup over 3 years\n. however , such patients can be logistically difficult to follow for long term followups .\nthe bpd - ds group was significantly younger than the rygbp group , but no differences were observed between the two groups at baseline in platelet counts , ggt or alt . body fat content and liver fat content , measured by imaging techniques such as dual energy x - ray absorptiometry or ultrasonography , would have been warranted to investigate if and how different fat distribution might influence the variables analyzed in this study . in conclusion , morbidly obese patients treated with rygbp and bpd - ds show a marked and sustained decrease in ggt and alt .\na significant reduction in platelets , a marker for inflammation and fibrosis in nafld , was observed in both groups after 1 year but only in bpd - ds over time , which may indicate improvements in general inflammatory status and particularly steatohepatitis .", "answer": "background . obesity is characterized by liver steatosis , chronic inflammation , and increased liver enzymes , that is , gamma - glutamyltransferase ( ggt ) and alanine aminotransferase ( alt ) , markers for nonalcoholic fatty liver disease ( nafld ) and liver fat content . increased platelet counts ( pcs ) \n are associated with inflammatory conditions and are a valuable biomarker of the degree of fibrosis in nafld . \n we investigated alterations in pc , ggt , and alt after biliopancreatic diversion with duodenal switch ( bpd - ds ) and roux - en - y gastric bypass ( rygbp ) . \n methods . ten morbidly obese patients ( body mass index , bmi : 53.5 3.8 kg / m2 ) who underwent bpd - ds were evaluated preoperatively ( baseline ) and 1 year ( 1st followup ) and 3 years ( 2nd followup ) after surgery and compared with 21 morbidly obese patients ( bmi : 42.3 5.2 kg / m2 ) who underwent rygbp . results . over the 3 years of followup , changes in bpd - ds and rygbp patients ( bpd - ds / rygbp ) were as follows : \n bmi ( 44%/24% ) , ggt ( 63%/52% ) , and alt ( 48%/62% ) . \n pc decreased ( 21% ) statistically significantly only in bpd - ds patients . \n conclusions . \n morbidly obese patients treated by rygbp or bpd - ds show sustained reductions in bmi , alt , and ggt . \n the decrease in pc and liver enzymes after bpd - ds may reflect a more pronounced decrease of liver - fat - content - related inflammation and , as a result , a lowered secondary thrombocytosis .", "id": 765} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute liver failure ( alf ) is a rare but life - threatening illness which occurs mostly in young adults without any known underlying liver disease [ 1 , 2 ] . in the united states ,\nthe most common cause of alf is acetaminophen overdose ( 39% ) but in 13% of cases , the causes are indeterminate .\nepstein - barr virus ( ebv ) is a dna virus associated with infectious mononucleosis ( i m ) in children and young adults .\nit may cause moderate and transitory increase of liver enzymes ; however , in rare cases , severe liver injury and even fatal alf may occur .\nwe report a case of successful orthotopic liver transplantation ( olt ) in a 67-year - old female who presented with ebv - associated alf .\na 67-year - old woman with bilateral osteoarthritis of the knee , hypothyroidism and recurrent deep vein thrombosis presented with 3 weeks of fatigue and a 1-week history of jaundice .\nher medications include diclofenac , rivaroxaban , desiccated thyroid , alprazolam , selenium and glucosamine .\nfour weeks prior to admission , the patient was found to have mildly elevated serum aminotransferases during a routine visit .\none week prior to admission , she reported to become jaundiced and her aminotransferases were found to be elevated to about 1,000\none day prior to admission , her serum alanine aminotransferase ( alt ) was 3,542 u / l , aspartate aminotransferase ( ast ) was 3,610\nu / l and her inr was 2.7 . on admission , her vital signs were normal , and a physical exam was positive only for jaundice .\nlaboratory findings included a white blood cell count of 13,200/l ( neutrophils 84.9% , lymphocytes 12.4% , monocytes 3.5% and eosinophils 0.2% ) .\nu / l , ast was 1,236 u / l , alp was 215 u / l and inr was 2.9 .\nhepatic artery , hepatic veins , and portal vein were patent , with a normal direction of flow by doppler study .\nserum acetaminophen level was 7 g / ml . hav antibody , hbsag , hcv and hev antibody were all negative .\nblood tests for human immunodeficiency virus ( hiv , hiv1/2 antibody and p24 antigen ) , cytomegalovirus ( cmv ) , rubella and rubeola were negative .\nantinuclear antibody , anti - mitochondrial antibody and anti - smooth muscle antibody were negative . the patient was initially diagnosed with alf possibly , secondary to diclofenac use , because she had begun to take diclofenac potassium 50 mg twice daily since 5 months ago .\nshe was admitted to the icu and received multiple transfusions of fresh - frozen plasma ( ffp ) to correct her coagulopathy .\nshe was given midodrine and octreotide and underwent hemodialysis for hepatorenal syndrome . despite multiple transfusions of ffp , her coagulopathy worsened , and her inr was 3.7 the following day .\nher serum alt and ast decreased rapidly in the following 2 days and the patient became more lethargic and somnolent , and difficult to arouse .\nfour days after admission , she underwent a successful liver transplantation from a cmv - negative , ebv ( igg ) positive cadaveric donor .\nthe explanted liver was significantly smaller than normal indicating acute failure of the liver ( fig .\nafter transplantation , she received thymoglobulin , methylprednisolone taper and was later switched to prednisone taper , and she also started tacrolimus 4 days after transplantation .\n( a ) small explanted liver weighing 720 g. ( b , c ) histologically , the liver showing 75% of parenchyma extinction and massive necrosis with sinusoidal lymphocytosis and atypical lymphocytes ( h&e , b : 100 ; c : 400 ) .\n( d ) ebv in situ hybridization ( left , 600 ) and cd20 immunostain ( right , 600 ) showing numerous ebv - positive atypical b lymphocytes . \nher histological report of the explanted liver showed that there was 75% massive hepatic parenchyma necrosis ( fig .\nthere were also acidophilic bodies , microvesicular steatosis and mild macrovesicular steatosis present in the residual hepatic parenchyma .\nthere was a mixed population of inflammatory cells with predominant lymphocytes with sinusoidal lymphocytosis ( fig .\n1d , left ) and positive for cd20 immunostain ( 1:100 dilution , horse radish peroxidase technique ; dako , carpenteria , ca ) ( fig .\nhsv staining of the liver tissue was negative although the serum antibodies were slightly higher than normal .\na review of the liver biopsy 5 days prior to admission showed about 25% hepatic parenchyma necrosis with bridging necrosis ( fig .\na whole blood assay for ebv dna using pcr of edta anticoagulated peripheral blood showed 462,000 copies / ml .\nshe was started on intravenous acyclovir immediately after the diagnosis of ebv infection , and later she was switched to oral acyclovir which was administered for 3 months .\ntwo weeks after transplantation , ebv viral capsid antigen ( vca)-igg test was positive and vca - igm was negative , ebv d early antigen ( ea - d ) and epstein - barr nuclear antigen ( ebna ) were negative .\none month later , the transplanted liver underwent biopsy and showed negative cd20 and ebv rna ( data not shown ) .\nthe patient is presently doing well 6 months after liver transplantation with no evidence of clinical ebv infection or lymphoproliferative disease .\n( a , b ) liver showing 25% parenchyma necrosis with bridging necrosis , acidophilic bodies , mixed inflammatory infiltrate and sinusoidal lymphocytosis ( a : 100 ; b : 400 ) .\n( c ) ebv in situ hybridization showing occasional ebv - positive b lymphocytes ( 400 , arrows ) .\nlt : liver transplant ; acv : acyclovir ; alp : alkaline phosphatase ; ast : aspartate aminotransferase ; alt : alanine aminotransferase .\nwe describe a case of alf - associated with ebv infection in a previously healthy elderly woman that underwent successful emergent liver transplantation .\nfulminant liver failure , is a sudden and severe hepatic injury in patients without previous liver diseases .\nthe clinical manifestation usually includes loss of hepatic function , coagulopathy , hepatic encephalopathy and in many cases , progressive multi - organ failure [ 1 , 2 ] . despite recent advances in intensive care management ,\nit has been reported that 5-year survival rate is about 80% in patients who underwent emergency liver transplantation for alf .\nthe etiologies of alf vary greatly by country and have evolved over time . in the unites states ,\ndrug - induced alf , mainly acetaminophen , accounts for about 58% of cases , and hepatitis a and b accounts for 14% of cases according to the us acute liver failure study group data .\nthese cases often follow a relatively insidious presentation before patients quickly develop liver failure , and rates of survival are poor without transplantation .\nrecent studies showed that the cause may be related to ebv infection . in our case\n, the cause of alf was initially thought to be diclofenac , because the patient had been taking diclofenac for about 5 months prior to admission , and other causes such as acetaminophen , infectious agents and metabolic diseases were excluded through serological tests ; however , the biopsy and blood ebv dna pcr results confirmed that ebv is the major cause of alf , and diclofenac may have played no or a minor role in this process .\nebv - associated alf is very rare , accounting for only 0.21 % of adult alf cases .\nit usually occurs in adults younger than 40 years of age , which is consistent with the fact that young adult patients tend to have symptomatic infectious mononucleosis [ 10 , 11 ] .\nit has been reported that patients with neoplasm , cmv and hiv and patients on immunosuppressant drugs are at high risk for ebv - associated alf , although recent studies also showed that immunocompetent patients can also develop alf , indicating that other unknown risk factors may also be involved in the development of ebv - associated alf [ 12 - 14 ] . in adult aged 60 years or older , there were only two cases of ebv - associated alf in the literature ; however , both of them had impaired immune system : one had just started steroids and the other had recent heart surgery [ 15 - 17 ] . in our case , the patient does not have any of the above mentioned problems and did not take any immunosuppressant medications .\nthis is the first case of ebv reactivation - associated alf in a healthy elderly patient .\nthis indicates that in older immunocompetent patients presenting with alf , a primary ebv infection or ebv reactivation should be considered when other causes have been excluded\n. early diagnosis of ebv - associated hepatitis was difficult as reliable diagnostic criteria are not clearly defined .\nmolecular approaches , such as ebv - dna pcr or eber - rish , are frequently used to diagnose ebv - related hepatitis [ 9 , 18 ] .\nserological ebv tests such as vca - igm , vca - igg , ea - d and ebna can also help to detect a recent infection or a prior infection , or a reactivated ebv infection , although they are not reliable , especially in the elderly , as they have significantly higher titers of the serum tests than young adults [ 9 , 18 ] . in our case ,\nthe liver biopsy 1 week before admission showed 25% hepatic necrosis , some atypical b lymphocytes with positive ebv rna . in explanted liver\n, there was over 75% necrosis , significantly increased atypical b cells and strongly positive expression of ebv rna , which is consistent with the progression of the liver failure .\nwe also tested the blood ebv level by pcr 4 days after liver transplantation and it was extremely high , indicating a severe active ebv infection .\nthe ebv serology tests 10 days after liver transplantation showed very high vca - igg but normal vca - igm , indicating that this is an ebv reactivation .\nmoreover , the liver enzyme showed cholestatic enzyme changes after transplantation with continuously increased alp .\nwe think that the increased alp was due to damage caused by ebv infection to the implanted liver .\ntreatment with acyclovir should be strongly considered after liver transplantation for alf from ebv to prevent infection of the liver graft during the period of high level immunosuppression .\nfirst , we were not able to diagnose ebv hepatitis until after evaluation of the explanted liver .\nliver transplantation could be potentially avoided if an early diagnosis of ebv hepatitis could have been made .\nsecond , the ebv pcr test was done after transplantation , when patient had already been on steroids .\nthe extremely high ebv pcr value may not reflect the severity of ebv infection , as steroids can suppress the immune system and ebv could replicate faster than expected .\nthird , the serological test was done 10 days after we started acyclovir , which may not show the initial changes of ebv infection .\nin addition , the use of diclofenac in this patient since a few months ago might have caused some initial injury to the liver .\ndiclofenac is reported to cause liver injuries by two main mechanisms , hypersensitivity and metabolic aberration [ 19 , 20 ] .\nacute liver injury caused by diclofenac is thought to be due to hypersensitivity and usually presents within days to a few weeks after starting diclofenac , which can result in fatal liver failure .\nmetabolic aberration can cause persistent mild liver injury and once diclofenac is stopped , the liver can recover quickly . in our patient , diclofenac might have caused mild liver injury initially ; however , the reactivation of ebv plays a major role in developing alf .\nwe are confident that ebv is the cause of alf in the patient based on liver enzyme changes , characteristic histopathological changes , and most importantly strong ebv rna expression in the explanted liver . in conclusion\n, our case demonstrates that ebv infection or reactivation may be under - recognized as a cause of alf .\nearly recognition and diagnosis is extremely important , however difficult . in both healthy young and elderly adults with alf\nliver biopsy should be strongly considered in patients with unexplained alf with hepatitis pattern and ebv rna by in situ hybridization should be mandatory if sinusoidal lymphocytosis is present .\nemergent liver transplantation is the only definitive treatment option , with very favorable prognosis for such patients .\ntreatment with acyclovir should be strongly considered after liver transplantation for alf from ebv to prevent infection of the liver graft during the period of high level immunosuppression .", "answer": "acute liver failure ( alf ) is a rare illness with a high mortality rate . \n the only favorable management is emergent liver transplantation . \n about 13% of alf cases have no clear etiology . \n epstein - barr virus ( ebv)-associated alf accounts for less than 1% of all alf cases , and is seen mostly in adults younger than 40 years . \n there are only a few cases of ebv - associated alf in elderly immunocompromised adults . \n we report a case of alf in an immunocompetent 67-year - old woman caused by ebv infection that was treated by orthotopic liver transplantation ( olt ) . \n the diagnosis of ebv - associated alf was established by ebv - dna polymerase chain reaction ( pcr ) and ebv - encoded rna ( eber - rna ) in situ hybridization ( eber - rish ) . \n the patient is currently doing well 6 months after transplantation without any evidence of clinical ebv infection . \n this case illustrates the importance of early recognition and diagnosis of ebv - associated alf by detection of ebv from liver biopsy , especially when patients are immunocompetent and other causes are excluded . to the best of our knowledge , \n this is the first case of ebv - associated alf present in an immunocompetent elderly female .", "id": 766} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nurinary tract infections ( utis ) are one of the inflammatory diseases produced by high multiplication of many pathogens in the urinary apparatus , resulting in alterations in the perfect function of the urinary tract and kidneys .\nuti is particularly a major problem for females ; nearly 5080% of the female population endures from uti at least once in lifetime and 20 - 50% of them will have recrudescent events ( 1 , 2 ) .\nescherichia coli is the most frequent pathogen responsible for up to 80% of utis ( 3 ) .\nthis bacteria is responsible for 85% and 50% of community and hospital acquired utis , respectively ( 4 ) .\nuropathogenic e. coli ( upec ) strains have special virulence factors , including pili or fimbriae , which mediate attachment to uroepithelial and vaginal cells , resistance to human serum bactericidal activity , haemolysin production , and increased amounts of k capsular antigen ( 5 ) .\nfurthermore , virulence factors of upec strains have a significant role in development of utis .\nthe most virulence factors dependent upon the upec include adhesions ( type 1 fimbriae , p fimbriae , curli mbriae , ambrial adhesion and flagellum ) , aerobactins , hemolysins , and cytotoxic necrotizing factor 1 .\nthe mentioned virulence factors are important in colonization of upec , extra - intestinal survival , and creation of cytopathic effects .\nin addition , the expression of special virulence factors of upec can contribute to uropathogenicity , as well as worsening of utis ( 1 , 6 , 7 ) . an essential step for beginning and development of uti is bacterial attachment to uroepithelial cells .\ne. coli attachment is mediated by ligands of bacteria ( generally small proteins placed at the tips of bacterial fimbriae ) which bind to host cell wall carbohydrate residues , working as receptors ( 5 ) .\ntherefore , the adherence of e. coli to host receptors is a function , usually mediated by adhesions of bacteria to host cell receptors ( 8) .\nthe bacterial attachment permits bacteria to resist mechanical elimination by the flow of urine and bladder emptying and increasing persistence of e. coli .\nupec strains produce different types of adhesins , including type 1 fimbriae , which are essential for recognition and attachment to urinary tract receptors ( 9 ) . among adhesions of upec ,\nthe adhesive subunit of type 1 fimbriae , fimh , is a major determinant , which has high tropism for urinary tract receptors ; thus , fimh adhesion is important in colonizing different niches of e. coli ( 10 ) .\nin addition , single - nucleotide polymorphism ( snp ) analysis of fimh is a screening tool for epidemiological typing of upec ( 11 , 12 ) . therefore , the research on bacterial virulence factors can result in expansion and development of new methods for diagnosis and prevention of utis .\nfor more subsequent investigations , the fimh gene was detected in upec strains isolated from hospitalized and out - patients with uti , referred to educational hospitals of shahrekord .\nthe present study was conducted for detection of the fimh virulence gene from upec isolated from both hospitalized patients and outpatients with uti , referred to educational hospitals of shahrekord , iran .\nin this study , 140 isolated e. coli strains from patients with uti were evaluated .\nthe isolates were collected from both hospitalized and non - hospitalized patients with utis from april to july 2012 from kashani and hajar hospitals , shahrekord , iran . hospitalized infections were characterized as patients who were confined to bed in hospital and non - hospitalized infections were characterized as infections in patients who had no prior contacts with hospitals or long - term care facilities two weeks prior to admission .\nthe samples were cultured on macconkey agar , blood agar and eosin methylene blue ( emb ) agar ( hi media , india ) .\nthe plates were incubated at 35c for 24 hours and pure isolates were characterized and identified according to gram staining and biochemical tests such as catalase , oxidase , indole production , citrate utilization , triple iron sugar , ortho - nitrophenyl--galactoside ( onpg ) test , and methyl red - voges proskauer , as described in standard bacteriological methods .\nall the above chemicals and media were purchased from sigma - aldrich ( germany ) .\ngenomic dna templates for pcr amplification were gained from overnight growth of bacterial isolates on luria - bertani agar ( hi media , india ) , pelleted by centrifugation , resuspended in 500 l of sterile deionized water , and boiled for 10 minutes .\nafter centrifugation of the boiled samples at 19000 g for five minutes , the supernatant was applied as the dna template for pcr .\nthe bacterial isolates were subjected to screening for the presence of the fimh gene by pcr .\nthe nucleotide sequence of the primers and the annealing temperature for amplification of the fimh gene by pcr are shown in table 1 .\npcr was carried out in 25 l containing 2.5 l of 10 pcr reaction buffer with mgcl2 ( 1.6 mm ) , 0.5 l ( 200 m ) of deoxynucleoside triphosphates mixture ( dntps , 10 mm ) , 0.5 l of each primer ( 10 pm/l ) , 2 l of the dna template ( 50 ng ) with 0.5 l ( 3 u/l ) taq dna polymerase . the amplification condition included an initial denaturation ( 96c for three minutes ) , 37 cycles ( 96c for 30 seconds , 64c for five minutes , 72c for 60 seconds ) and a final extension ( 72c for fiv eminutes ) .\nthe pcr amplifications were performed on a thermocycler tc-512 ( bio - techne , cambridge uk ) and the pcr products were analyzed by polyacrylamide gel ( 8% ) electrophoresis . a molecular marker ( fermentas sm0321 , 100 bp ) was used to assess the pcr products sizes .\nin this study , 140 isolated e. coli strains from patients with uti were evaluated .\nthe isolates were collected from both hospitalized and non - hospitalized patients with utis from april to july 2012 from kashani and hajar hospitals , shahrekord , iran . hospitalized infections were characterized as patients who were confined to bed in hospital and non - hospitalized infections were characterized as infections in patients who had no prior contacts with hospitals or long - term care facilities two weeks prior to admission .\nthe samples were cultured on macconkey agar , blood agar and eosin methylene blue ( emb ) agar ( hi media , india ) .\nthe plates were incubated at 35c for 24 hours and pure isolates were characterized and identified according to gram staining and biochemical tests such as catalase , oxidase , indole production , citrate utilization , triple iron sugar , ortho - nitrophenyl--galactoside ( onpg ) test , and methyl red - voges proskauer , as described in standard bacteriological methods .\nall the above chemicals and media were purchased from sigma - aldrich ( germany ) .\ngenomic dna templates for pcr amplification were gained from overnight growth of bacterial isolates on luria - bertani agar ( hi media , india ) , pelleted by centrifugation , resuspended in 500 l of sterile deionized water , and boiled for 10 minutes .\nafter centrifugation of the boiled samples at 19000 g for five minutes , the supernatant was applied as the dna template for pcr .\nthe bacterial isolates were subjected to screening for the presence of the fimh gene by pcr .\nthe nucleotide sequence of the primers and the annealing temperature for amplification of the fimh gene by pcr are shown in table 1 .\npcr was carried out in 25 l containing 2.5 l of 10 pcr reaction buffer with mgcl2 ( 1.6 mm ) , 0.5 l ( 200 m ) of deoxynucleoside triphosphates mixture ( dntps , 10 mm ) , 0.5 l of each primer ( 10 pm/l ) , 2 l of the dna template ( 50 ng ) with 0.5 l ( 3 u/l ) taq dna polymerase . the amplification condition included an initial denaturation ( 96c for three minutes ) , 37 cycles ( 96c for 30 seconds , 64c for five minutes , 72c for 60 seconds ) and a final extension ( 72c for fiv eminutes ) .\nthe pcr amplifications were performed on a thermocycler tc-512 ( bio - techne , cambridge uk ) and the pcr products were analyzed by polyacrylamide gel ( 8% ) electrophoresis .\na molecular marker ( fermentas sm0321 , 100 bp ) was used to assess the pcr products sizes .\nthe fimh gene was amplified using specific primers and appeared as a band of about 164 bp on polyacrylamide gel ( figure 1 ) .\nthe fimh gene was found in 130 isolates ( 92.8% ) of upec . of the 130\nisolates positive for the fimh gene , 62 ( 47.7% ) and 68 ( 52.3% ) belonged to hospitalized patients and outpatients , respectively .\ncoli clinical isolates containing the fimh gene ( 164 bp ) ; lane 13,negative control ( without dna template ) ; lanes 14 - 17 : e. coli clinical isolates containing the fimh gene ( 164 bp ) .\nthe onset of uti results from the ability of upec attachment to urinary tract epithelial cells by specific adhesions including type 1 fimbriae ( 13 ) .\nupec strains have many virulence factors which enhance their capacity to colonize in the urogenital tract .\nattachment to the urothelial cell surface is mediated by fimh adhesion , placed at the tip of the type 1 fimbriae , which prevents bacterial washout by urine flow and starts bacterial invasion ( 4 , 14 ) . since the fimh virulence factor associated with uti cases\nwas not widely determined from the upec isolated from both hospitalized patients and outpatients with utis referred to educational hospitals of shahrekord , iran , the prevalence of the fimh gene was examined .\nthe presence of the fimh gene was confirmed by pcr and the results indicated that the fimh gene was present in 130 upec isolates ( 92.8% ) ; 62 isolates ( 47.7% ) of hospitalized patients and 68 ( 52.3% ) of outpatients .\nthis showed that most of the upec strains had the fimh gene and our results were almost in accordance with the results of previous literature .\n( 15 ) reported that among the studied virulence genes of upec strains , the fimh gene was the most prevalent virulence gene and was found in 68% ( 61/90 ) of the uti isolates .\n( 16 ) studied 18 upec isolates collected from females and found that the fimh gene was the most prevalent virulence factor and 100% of the isolates had that gene . in another study ,\n17 ) demonstrated that the fimh gene was the most frequent virulence gene and was detected in 98% of e. coli strains isolated from patient with utis .\n( 7 ) evaluated the distribution of virulence genes among the studied upec and showed that the prevalence of different virulence genes varied from 10% for the cnf gene to 80% for the fimh gene .\nin addition , arabi et al . ( 18 ) investigated the frequency of fimh and other adhesions genes in upec and determined the fimh gene frequency as 87.7% .\napart from investigation on evaluation of the fimh gene in upec strains , this gene has been detected in other strains of e. coli .\nfor example , kaczmarek et al . ( 13 ) evaluated and detected the genes encoding virulence factors among e. coli strains with k1 antigen as well as the non - k1 e. coli strains .\nthey found that the fimh gene existed in the whole tested e. coli k1strains as well as in 97.0% of non - k1 strains .\n( 19 ) also reported that the fimh gene was present in 54.55% of avian pathogenic e. coli ( apec ) strains which are pathogenic for birds . in another study ,\n20 ) showed that in enterohemorrhagic e. coli ( ehec ) strains , the fimh gene was conveyed by the majority of non - o157:h7 e. coli strains ( 97% ) and by all the o157:h7 e. coli strains .\n( 21 ) detected the fimh gene in all the e. coli isolates from bovine mastitis .\nmoreover , fimh snp analysis is a typing tool for epidemiological studying of community- and hospital - associated e. coli isolates and could be used as an easy , cheap screening test for genotypic analyses of upec ( 11 , 12 ) .\nwe can conclude that type 1 fimbriae is present among upec as well as other strains of e. coli , to the extent that the fimh gene was detected in more than 90% of the e. coli strains . the high binding ability of fimh could result in increased bacterial binding to target cells and increased pathogenicity of e. coli ; thus , fimh could be used to design vaccine for prevention of e. coli infections by blocking the bacterial attachment and colonization .\nin addition , fimh could be used as a tool for the extension of rapid detection - based assays .", "answer": "background : urinary tract infections ( utis ) are one of main health problems caused by many microorganisms , including uropathogenic escherichia coli ( upec ) . \n upec strains are the most frequent pathogens responsible for 85% and 50% of community and hospital acquired utis , respectively . \n upec strains have special virulence factors , including type 1 fimbriae , which can result in worsening of utis.objectives:this study was performed to detect type 1 fimbriae ( the fimh gene ) among upec strains by molecular method.materials and methods : a total of 140 isolated e. coli strains from patients with uti were identified using biochemical tests and then evaluated for the fimh gene by polymerase chain reaction ( pcr ) analysis.results:the upec isolates were identified using biochemical tests and were screened by pcr . \n the fimh gene was amplified using specific primers and showed a band about 164 bp . \n the fimh gene was found in 130 isolates ( 92.8% ) of the upec strains . \n of 130 isolates positive for the fimh gene , 62 ( 47.7% ) and 68 ( 52.3% ) belonged to hospitalized patients and outpatients , respectively.conclusions:the results of this study indicated that more than 90% of e. coli isolates harbored the fimh gene . the high binding ability of fimh could result in the increased pathogenicity of e. coli ; thus , fimh could be used as a possible diagnostic marker and/or vaccine candidate .", "id": 767} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nganglioneuromas are rare benign tumors of neural crest origin ; they arise from peripheral sympathetic ganglia or the adrenal glands .\nthese tumors are most commonly discovered in older pediatric patients or adults ; they are discovered incidentally , through thoracic or abdominal imaging studies performed for unrelated conditions .\nintracranial involvement of ganglioneuromas is extremely rare ( 1 , 2 ) , and there has been only one report of ganglioneuroma arising from the trigeminal nerve .\nwe report a very rare case of trigeminal ganglioneuroma in the prepontine and cerebellopontine angle cistern , in a 44-year - old female and describe the magnetic resonance ( mr ) imaging characteristics , including diffusion - weighted imaging ( dwi ) findings .\na 44-year - old female was admitted to our hospital because of a 2-year history of facial pain and numbness in the left side .\nthe patient complained of an intermittent stabbing pain and numbness over the left zygomatic region .\na brain mr imaging study was performed with a 3 t unit ( magnetom triotim , siemens , erlangen , germany ) , which revealed a 2 1.8 1.5 cm well - circumscribed mass in the prepontine and cerebellopontine angle cistern on the left side ( fig .\nthe left fifth cranial nerve was displaced superomedially , and the seventh - eighth nerve complex inferiorly by the mass .\nthe mass showed homogeneous iso - signal intensity on a t1-weighted image relative to the brain parenchyma ( fig .\n1a ) as well as heterogeneous increased signal intensity on a t2-weighted image ( fig .\nthe apparent diffusion coefficient ( adc ) values were obtained using a circular region of interest with a diameter of 6 mm at 4 nonoverlapping locations in the tumor ( fig .\nthe mean adc values obtained with b values of 0 and 1000 sec / mm of the tumor were 0.72 10 mm / s , compared to 3.01 10 mm / s for csf ( measured in the fourth ventricle ) and 0.71 10 mm / s for adjacent brain tissue ( measured in the pons ) .\nthe preoperative diagnosis for this poorly enhancing mass with a dwi high signal intensity lesion in the prepontine and cerebellopontine angle cistern was an epidermoid cyst .\n, a well - circumscribed solid mass was found to be firmly attached to the trigeminal nerve .\nhistopathologic examination demonstrated a benign tumor composed of mature ganglion cells and spindle - shaped cells in an abundant collagenous stroma ( fig .\npostoperatively , facial pain and numbness disappeared , and follow - up mr imaging , obtained 16 months later showed no evidence of tumor recurrence .\nganglioneuromas are typically found within the posterior mediastinum and retroperitoneum , though less common locations include the adrenal medulla , parapharyngeal region , and visceral ganglia .\nrarely , ganglioneuromas have been observed in the tongue , prostate , skin , and bone ( 3 ) .\nintracranial ganglioneuroma is extremely rare , and only a few cases have been reported in previous literature ( 1 , 2 ) .\nhistologically , these tumors are composed of single or clustered mature ganglion cells and mature schwann cells ( 3 ) .\ntypical radiologic findings of ganglioneuroma arising from the peripheral sympathetic nerve have been described . at ct , ganglioneuromas are well - demarcated hypoattenuated lesions , with calcifications in 20 - 42% of cases .\nthese tumors are not significantly enhanced after the administration of contrast materials , but delayed ct images can show slight or moderate enhancement ( 3 , 4 ) . at mr , ganglioneuromas are generally hypointense on t1-weighted images and heterogeneously hyperintense on t2-weighted images with respect to adjacent muscle .\n( 1 ) reported the first case of trigeminal ganglioneuroma and described conventional mr imaging findings , which are similar to those of thoracoabdominal ganglioneuromas . mr images included in their report demonstrated a well - defined mass with low signal intensity on a t1-weighted image , high signal intensity on a t2-weighted image , and relatively homogenous enhancement on a post - contrast t1-weighted image . in our patient ,\nthe lesion was iso - signal intense to the adjacent pons on the t1-weighted image and showed slightly increased signal intensity on the t2-weighted image .\nit has previously been reported that ganglioneuromas with markedly high signal intensity on a t2-weighted image histologically consist of a large amount of myxoid stroma and relatively few cellular components and collagen fibers .\nin contrast , tumors with intermediate to subtle high signal intensities on a t2-weighted image , as in our case , consisted of numerous cellular and fibrous components and few myxoid stroma ( 4 , 5 ) . in our case , the mass showed poor enhancement on a postcontrast t1-weighted image .\nthoracoabdominal ganglioneuromas can demonstrate gradually increasing enhancement with dynamic mr imaging ( 3 - 5 ) .\ndiffusion - weighed imaging findings and adc values with regard to intracranial ganglioneuroma have not been published previously .\nour case showed a homogeneous hyperintense signal throughout the tumor , on a dwi , and revealed a mean tumor adc value of 0.72 10 mm / s .\n( 6 ) recently reported dwi findings of the ganglioneuromas / ganglioneuroblastomas originating from the thoracoabdominal sympathetic nervous system .\nthese tumors showed relatively high adc values ( mean adc : 1.60 10 mm / s , range 1.13 - 1.99 10 mm / s ) .\nthe differences between gahr 's cases and our case may be due to the different tumor histopathologies .\none might postulate that high cellular density and scanty myxoid stroma , revealed through histopathology , may be attributed to relatively low adc values in our case .\n( 7 ) reported that focal central hemorrhages were observed in 2 of 17 adrenal ganglioneuromas .\nour case showed no intratumoral susceptibility signals on gradient echo images , as well as absence of intratumoral hemorrhage or calcification with histopathology .\nan epidermoid cyst should be included in the differential diagnosis of t2-increased signal intensity lesions in the prepontine and cerebellopontine angle cisterns .\nthe high signal intensity of epidermoid cysts with dwi is caused by the intrinsic t2 shine - through effects of the lesion .\nreported adc values of intracranial epidermoid cysts range from 0.98 10 mm / s up to 1.36 10 mm / s ( 8) ; these are higher than the values of trigeminal ganglioneuroma in our case .\nother differential diagnoses of masses in the prepontine and cerebellopontine angle cisterns include schwannoma , meningioma , neurofibroma , and metastasis .\nthe majority of these tumors do not show high signal intensity with dwi and demonstrate relatively strong enhancement on post - contrast t1-weighted images .\nother rare tumors that have been reported to occur in the trigeminal nerve include benign triton tumor ( neuromuscular hamartoma ) and ganglioglioma .\nneuromuscular hamartomas were reported to be profoundly hypointense on t2-weighted images and demonstrated mild homogenous contrast enhancement ( 9 ) .\na trigeminal ganglioglioma may be difficult to distinguish from a ganglioneuroma like that in our case .\nthis tumor showed a nonspecific homogenous mr signal intensity indistinguishable from the adjacent brain stem with all imaging sequences and no contrast enhancement ( 10 ) .\ndwi findings of neuromuscular hamartoma and ganglioglioma , arising from the trigeminal nerve have not been reported .\ntrigeminal ganglioneuroma is a very rare tumor ; however , this tumor should be considered in the differential diagnosis of tumors with low adc values in the prepontine and cerebellopontine angle cistern .\ntrigeminal ganglioneuroma is a very rare tumor ; however , this tumor should be considered in the differential diagnosis of tumors with low adc values in the prepontine and cerebellopontine angle cistern .", "answer": "a case of intracranial ganglioneuroma arising from the trigeminal nerve in the pontine and cerebellopontine angle cistern , in a 44-year - old female , is presented with an emphasis on diffusion - weighted imaging findings . \n we will discuss on how the tumor in the very unusual location should be differentiated particularly focused on diffusion - weighted imaging findings .", "id": 768} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncavernous sinus thrombosis ( cst ) was first reported by bright et al . in 18311 .\ncst is an infectious disease that is potentially fatal if it is not treated in its early stage .\nfurthermore , despite treatment , complications of cst such as cranial nerve dysfunction may remain .\nthere are very few reports of cst related to periodontal disease or to tooth extraction3 .\nthe authors present a case in which misdiagnosis and inappropriate treatment of a buccal cheek laceration due to an ill - fitting denture resulted in a buccal space abscess that progressed into cst .\na 65-year - old man with no past medical history presented to the emergency room with facial swelling and fever .\ntwo weeks earlier , he began having trismus and pain on the mandibular left side .\nthe patient was prescribed prednisolone , cyclobenzaprine , steroids and muscle relaxants and was advised to frequently apply moist hot packs .\nthe patient 's symptoms persisted and he developed spiking fevers with delirium . in the emergency room ,\nhis vital signs included blood pressure 151/82 mmhg , pulse 95 beats per minute , temperature 39.3 , and respiratory rate 12/min .\na complete blood count revealed a white blood cell ( wbc ) count of 19,110/l with 92.8% neutrophils , a erythrocyte sedimentation rate ( esr ) of 89 mm / h and c - reactive protein ( crp ) of 279.2 mg / l .\ncomputed tomography ( ct ) showed an abscess in the buccal and pterygomandibular space spreading into the temporal space.(fig .\n1 ) the patient 's mental status was assessed with questions about his personal information .\nhe had three teeth on the right mandibular side , and the left buccal cheek was swollen with a 1 cm laceration .\nhowever , because the patient showed clinical signs of infection associated with buccal , pterygomandibular , and temporal space abscesses , he was admitted to the hospital .\nempirical antibiotic treatment was initiated with flomoxef 2 g / day , metronidazole 1.5 g / day , and isepamicin sulfate 400 mg / day . on the day of hospitalization\nofloxacin otic solution was topically applied to the external auditory canal and the occlusive dressing was changed daily . on the second day of hospitalization ,\na spinal tap revealed cerebrospinal fluid turbidity suggestive of central nervous system ( cns ) infection .\nas per recommendations from internal medicine , and neurology , the antibiotic regimen was changed to ceftazidime 4 g / day and vancomycin 2.7 g / day to cover the cns infection and potential methicillin - resistance staphylococcus aureus ( mrsa ) . on the third day of hospitalization , an oral and maxillofacial surgeon performed intraoral incision and drainage of the buccal and pterygomandibular spaces .\nresults of a magnetic resonance image ( mri ) included a dilated superior ophthalmic vein , bulging cavernous sinus contour , and septic thrombi in the cavernous sinus .\n2 ) antimicrobial sensitivity testing identified methicillin - sensitive staphylococcus aureus ( mssa ) and therefore the antibiotic regimen was changed to nafcillin 12 g / day .\nhis buccal swelling decreased , he recovered the ability to open his mouth , and his visual acuity and extremity sensation improved .\nwbc , esr , and crp counts also improved.(table 1 ) with reduced swelling , we discovered an ill - fitting denture .\ncst is a rare condition in which blood clots form within the cavernous sinus , a large collection of thin - walled veins .\nseptic cst may be caused by sinusitis , otitis , odontogenic infection , or facial cellulitis .\nthe most frequent cause of septic cst is sinusitis in the sphenoid or ethmoidal sinuses .\ndental infections account for < 10% of septic cst cases , and most of these cases are related to maxillary infection4 .\neagleton5 proposed the following criteria for cst diagnosis : a known site of infection ; blood stream infection ( sepsis ) ; early obstructive signs ( such as retinal vein fullness , proptosis , exophthalmus , and collateral venous circulation ) ; ocular nerve paralysis ( via lesions of cranial nerves iii , iv , v , and iv ) ; surrounding soft tissue abscesses ( of the orbit , occiput , neck or nasopharynx ) ; and symptoms of a complicated disease ( such as headache , papilledema , and meningeal signs ) .\nother potential pathogens include pneumococcus , bacteroides , fusobacterium , proteus , haemophilus , pseudomonas , and corynebacterium6 .\nvenous flow is bidirectional in the cerebral vein , emissary vein , and dural sinus because these vessels do not have valves .\ntherefore , bacteria or thrombi from another facial region can spread to the cavernous sinus via the facial vein or pterygoid plexus7 .\nophthalmoplegia is extraocular muscle weakness that results ( in cst ) when cranial nerves iii , iv , and/or vi are damaged due to their passage through the cavernous sinus .\nother symptoms of lethargy , headache , periorbital swelling , papilledema , and venous engorgement occur in 50%-80% of patients . decreased visual acuity , sluggish / dilated pupil , periorbital sensory loss , and decreased corneal reflex are less frequent symptoms that occur in < 50% of patients .\n. early symptoms of orbital cellulitis are similar to those of cst and include periorbital swelling , proptosis , chemosis , fever and impaired vision .\ncst is included in the differential diagnosis when the above symptoms present bilaterally or when there is sensory loss in the periocular area , papilledema , and pupillary dilation9 .\ncoronal ct reveals that the lateral wall of the cavernous sinus is flat or convex instead of its normal concave shape . additionally , irregular filling defects due to thrombi , and superior ophthalmic vein dilation are often observed .\nmri is useful when the ct images are not clear or when the infection has spread to surrounding tissues including the brain and pituitary gland10,11 . in the past\nthese imaging techniques are no longer recommended because they increase the risks of the infection spreading and thrombosis12 .\noptimal therapy for cst includes the concomitant administration of nafcillin , metronidazole , and ceftriaxone / cefotaxime .\nsurgical interventions are indicated when the primary site of infection is sinusitis , or a dental infection . in the case of a serious infection ,\none may consider direct surgical drainage of the cavernous sinus ; however , this approach is difficult and complications are likely to arise7 .\ncorticosteroid therapy must be considered if adrenal insufficiency occurs due to cranial nerve dysfunction or pituitary necrosis13 .\nsome studies have reported that anticoagulating with heparin , for example , within seven days after cst reduces the mortality rate14 .\nhowever , anticoagulation increases the risk of intracranial and/or systemic hemorrhage , and therefore should be used with caution15 . in this case , it was difficult to confirm the source of infection because the patient 's buccal cheek swelling and trismus prevented adequate intraoral examination .\nthe only suspicious finding was a small laceration on left buccal mucosa . generally , odontogenic infections arise from the teeth themselves or from periodontal tissue . therefore , it was difficult to confirm that this severe infection originated from a small laceration in a patient with no medical history .\nanother dentist who examined the patient two weeks before his presentation had misdiagnosed him with temporomandibular joint symptoms and myofascial pain .\nadministration of moist hot packs and prednisolone may have actually facilitated the infection 's progression .\ncst treatment must include proper management of the primary infection site and empiric antibiotics considering the possible pathogens .\ncst presents with inconsistent symptoms , and therefore it is essential to collaborate with various departments including neurology , ophthalmology , otorhinolaryngology , and internal medicine .\nit presents with proptosis , chemosis , periorbital swelling and other typical signs of infection including as fever , pain and swelling .\nclinicians in oral and maxillofacial surgery should be aware of cst and should consider it in patients with facial swelling .", "answer": "cavernous sinus thrombosis not only presents with constitutional symptoms including fever , pain and swelling but also with specific findings such as proptosis , chemosis , periorbital swelling , and cranial nerve palsies . \n it is known to occur secondary to the spread of paranasal sinus infections in the nose , ethmoidal and sphenoidal sinuses . however , paranasal sinus infection of dental origin is rare . \n the following is a case of cavernous sinus thrombosis due to the spread of an abscess in the buccal and pterygomandibular spaces via buccal mucosal laceration .", "id": 769} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin this issue of the jem , two articles describe a potential role for two bacterial toxins in the modulation of the immune system by interfering with t cell signaling . using an in vitro jurkat t cell system , gerke et al .\n( 8) report that yersinia pseudotuberculosis inhibits t cell activation and that the inhibitory activity was strictly dependent on the yersinia outer protein h ( yoph ) , a potent tyrosine phosphatase that is delivered to host cells by a bacterially encoded type iii protein secretion system .\nprevious studies by a number of laboratories have identified several tyrosine phosphorylated proteins as apparent targets for the tyrosine phosphatase activity of yoph in cell culture systems .\nthese include p130cas , focal adhesion kinase , and paxillin in hela cells , and fyb / slap130 , p130cas , and skap55 in macrophages ( 912 ) . in general ,\nthese are proteins involved in integrin signaling , which is consistent with the proposed role of yoph as an antiphagocytic molecule .\nmore recent studies have shown that yoph can also inhibit t cell signaling in - vitro and that this activity could be correlated with the presence of yoph and the dephosphorylation of the tyrosine kinase lck ( 13 ) .\n( 8) have now extended those studies and added the t cell signaling adaptor proteins lat and slp-76 to the list of potential yoph substrates .\nthese adaptor proteins are essential for the transduction of signals from the t cell receptor and its associated tyrosine kinases , and their tyrosine phosphorylation is required for their activities .\n( 8) argue that tyrosine dephosphorylation of these adaptor proteins by yoph is responsible for the observed inhibition of t cell receptor signaling after yersinia infection of cultured jurkat t cells .\nthey also present data that argue that both of these proteins are high affinity substrates of yoph , presumably requiring small amounts of translocated toxin to be targeted for dephosphorylation . in the second article , rossi paccani et al .\n( 14 ) report that anthrax toxin also disrupts t cell signaling but by a completely different mechanism . anthrax toxin , which is produced by bacillus anthracis , is composed of two enzymatic or a subunits known as edema factor ( ef ) and lethal factor ( lf ) that alternatively associate with a b subunit , known as protective antigen , which mediates their delivery into target cells ( 15 ) .\nef is a potent calcium / calmodulin - dependent adenylate cyclase , which causes a massive increase of cyclic amp in intoxicated cells and global disruption of cell signaling .\nlf is a zinc - dependent protease that specifically disrupts the mitogen - activated protein ( map ) kinase signaling pathways by cleaving the activating map kinase kinases mek1/2 and mkk3 , mkk4 , mkk6 , and mkk7 ( 1619 ) .\n( 14 ) showed that treatment of peripheral blood lymphocytes with protective antigen in combination with either lf or ef effectively blocked t cell signaling as measured by the expression levels of the surface activation markers cd69 and cd25 , the production of cytokines , and cell proliferation .\ngiven the ubiquitous presence of the anthrax toxin receptors and the essential role for map kinases and camp in t cell signaling , the results presented by rossi paccani et al .\nthe broader issue raised by these two and other studies with other bacterial toxins that disrupt immune cell function in vitro , however , is the in vivo relevance of the findings .\ndo these pathogens specifically interfere with t cell signaling during the course of an infection ? unfortunately , in vitro studies , although useful to provide testable hypotheses , can not provide answers to these important questions\n( 8) make a strong case for slp-76 and lat as high affinity substrates for this tyrosine phosphatase and hence of potential relevance during infection when presumably the pathogen would deliver small quantities of this toxin .\nindeed , it is often the case that under vitro experimental conditions , cells are exposed to toxin quantities not usually delivered during actual infections .\nnevertheless , it is not known how much yoph is delivered by yersinia during infection , and there is no evidence demonstrating that yersinia hampers t cell function during infection .\nyersinia infections are usually acute ( 20 ) , arguing against the need for these pathogens to counteract the host - specific adaptive immune responses during infection . however , although rare , chronic infections are sometimes observed ( 21 , 22 ) , and in those cases , the ability to interfere with t cell function might be useful to the pathogen .\nwhether this function of yoph has been specifically selected by evolution or is simply a by - product of another of its demonstrated functions , such as disruption of macrophages during acute infection , remains to be established .\nanthrax toxin possesses even a more difficult challenge because its biochemical activity ( such as inhibition of map kinase signaling ) can potentially affect a large number of cellular processes .\ntherefore , the ability of anthrax toxin to inhibit map kinase signaling can result in the in vitro inhibition of any of the rather large number of intracellular signaling pathways that involve these kinases , regardless of their relevance during infection .\nfor example , if added to cultured neurons , anthrax toxin would certainly prevent neurite outgrowth , a process strictly dependent on map kinase signaling ( 23 )\n. however , it would be hard to argue that this is a relevant function for the toxin during infection . by the same token , anthrax toxin\npredictably inhibited in vitro t cell signaling , a process strictly dependent on map kinase signaling .\nhowever , more experiments will be required to establish whether this activity of the toxin is important during infection .\nif untreated , b. anthracis infections are usually hyper acute ( 24 ) ; therefore , inhibiting t cell signaling may not provide a significant advantage to the pathogen . on occasions\n, b. anthracis can be associated with sub - acute infections ( such as cutaneous anthrax ; reference 24 ) , in which case inhibition of t cell function may provide some advantages to the pathogen . in any case , because b. anthracis is most likely an accidental \npathogen of mammals , it is unlikely that evolution may have played any role in directly shaping the effects of anthrax toxin on t cells . therefore , this activity might be more a byproduct , relevant or not , of other activities of this toxin in the normal ecology of b. anthracis . although every pathogen must contend with the onslaught of the innate immune responses , it is not necessarily the case that every pathogen must counteract the acquired immune response to fulfill its replication program . for most pathogens that cause acute infections , their life cycle within the host is most often over by the time the naive host mounts a meaningful acquired immune response capable of controlling the infection .\nin fact , most infections with pathogens that have coevolved with their hosts are indeed asymptomatic , do not lead to overt harm , and most often result in protective convalescent immunity . on the other hand ,\npathogens that cause persistent infections might be under strong evolutionary pressure to evolve specific mechanisms to avoid acquired immune responses .\nindeed , mechanisms of antigenic variation or specific inhibition of antigen presentation evolved by microbial pathogens are well documented ( 25 ) .\nfor example , many viral pathogens specifically interfere , by a variety of mechanisms , with both major histocompatibility class i and ii antigen - presenting pathways ( 26 , 27 ) .\nin addition , many viral , bacterial , and protozoan pathogens undergo rapid antigenic variation to evade the onslaught of the acquired immune response ( 2830 ) . whether inhibition of t cell signaling by anthrax or yoph toxins should be added to the list of pathogenic mechanisms specifically evolved to counter the acquired immune response", "answer": "microorganisms that cause persistent infection often exhibit specific adaptations that allow them to avoid the adaptive immune response . recently \n , several bacterial toxins have been shown in vitro to disrupt immune cell functions . \n however , it remains to be established whether these activities are relevant during infection and whether these toxins have specifically evolved to disrupt the adaptive immune system .", "id": 770} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe most important goal of rehabilitation for a lower limb amputee is the independent \n performance of daily activities through restoration of functional walking ability .\nmiller et al . \n reported that 52% of prosthesis users experienced falls and 49% of amputees have a fear of \n falling .\nit also said that the fear of falling limits the daily movement of amputees and \n causes further deterioration of the balance ability required for walking1 .\ntherefore , physical therapy for lower limb \n amputees should be focused on the prevention of falls during movement / walking for the \n improvement of everyday activities . for this purpose , it is necessary to properly evaluate \n the balance ability of amputees and to perform training to improve the balance ability based \n on the results of that evaluation .\nthe objectives of the present study were to elucidate \n what type of compensatory movement and postural strategy are used by lower limb amputees for \n posture control during the period from prosthesis fitting to hospital discharge by analyzing \n the muscle activity patterns of the lower limb muscles and to elucidate the changes over \n time in the muscle activity pattern during the course of physical therapy .\nelderly patients \n also have a higher risk of falling than younger patients because of biomechanical , \n physiological , and psychological differences .\nhowever , no study has yet focused on comparing \n time - dependant changes in muscle activity patterns between younger and elderly patients . \n\ntherefore , the other purpose of this study was to reveal the differences in muscle activity \n patterns during standing between younger and elderly patients .\na young male , 34 years old , and an elderly female , 84 years old , who had a lower limb \n amputated were the subjects .\nneither of the patients had a history of orthopedic or \n neurological disease in the unaffected lower limb or the trunk . a patient who undergoes \n below - knee amputation due to diabetes\nhas a normal deep sensation in the unaffected ankle \n joint . in both of our cases ,\nthe fitting between the socket and the stump on wearing was \n well adjusted with no pain in the stump .\nthe prosthesis used by the lower limb amputees was a total \n surface bearing liner type and a sach foot ( table \n 1table 1 .\ncharacteristics of the subjectssubjectssexage ( year)height ( cm)weight ( kg)amputation sitesocketankle jointcauseweek to start pt after amputationweek to wear prosthesis after amputationweek to discharge after wearing prosthesis for \n the first timeyoungm3317572right bkatsbsachtumor174elderf8515045left bkatsbsachdiabetes1514 m : male , f : female , bka : below knee amputee , tsb : total surface bearing , sach : solid \n ankle cushion heel ; j - foot m1170 , pt : physical therapy ) .\nsurface electromyography ( emg ) measurements were performed of the \n gastrocnemius medial head ( ga ) of the unaffected lower limb .\nthe electrodes were placed on \n the most prominent bulge of the ga muscle following seniam guidelines .\nafter sufficient \n treatment with skinpure to reduce the inter - electrode resistance to no more than 10 k on \n the skin , disposable electrodes ( blue sensor , nf-50-k / w , ambu ) were attached at an \n inter - electrode distance of 2 cm .\nthe emg signals were amplified ( to 1.0 mv ) and band - pass \n filtered between 201,000 hz using a synact mt-11 ( nec corp . , tokyo , japan ) .\nthe emg signals \n were digitized using a waveform analysis system , power lab 16s ( ad instruments ltd , hasting , \n uk ) , at a sampling frequency of 1,000 hz , and stored on a personal computer for off - line \n analysis .\nafter data input , waveform processing was performed using waveform analysis \n software , chart36.8 , ad instruments .\ntwo different tasks of maintaining the static standing \n position were performed on the floor .\nthe test subjects were asked to stand on the floor \n with their feet shoulder - width apart and look at a point set at 1 m distance to the front at \n the height of the eye for 10 seconds .\nthe first task , reference task , was to maintain \n upright standing position on the prosthesis while holding parallel bars .\nthe second task , \n experimental task , was forward weight shift while maintaining the standing position without \n grasping the parallel bars .\nthe recorded data were smoothed using the root mean square ( rms ) \n value of every 100 msec using waveform analysis software .\nthe reference contraction is \n judged to be reliable by being reproducible , giving approximately equal results within \n subjects over trial .\ntherefore , we used the emg of another task as a reference contraction \n for emg normalization . the normalized level of % rmsemg was determined using the following \n formula .\nm : male , f : female , bka : below knee amputee , tsb : total surface bearing , sach : solid \n ankle cushion heel ; j - foot m1170 , pt : physical therapy % rmsemg = experimental task rmsemg ( second task ) / reference task rmsemg ( first task ) \n 100% maximum walking speed was measured in 10 m walking .\ndepending on the condition at the time of the measurements , subjects \n were allowed to use a crutch , or a single cane on the unaffected side while walking .\nthe \n surface muscle activity and the walking speed were measured once a week , a total of four \n occasions , starting on the day of prosthesis fitting ( first week ) .\nthis study was conducted \n after approval was obtained from the ethics committee of tohoku university graduate school \n of medicine .\nthe study patients were sufficiently informed about the purpose and methods of \n the study , and their consent to participation was obtained .\nwhen the time - dependent changes in muscular activity of ga , which is the most active muscle \n in the standing position , were investigated in the forward weight shift task , two unique \n patterns were observed . for the younger subject ,\nno muscle activity of ga was observed in \n the standing position tasks in the first week , but the amount of muscular activity of ga \n gradually increased over time . on the other hand , for the elderly subject , increased \n activity of ga was observed in the forward weight shift task in the first week , when the \n prosthesis was worn for the first time , followed by a gradual decrease in activity over time \n ( table 2table 2 .\ntime shift of activity in ga ( % rmsemg ) and walking speed ( m / min)week%rmsemg ( % ) mws ( m / min)youngerelderlyyoungerelderlyfirst0.6618.4348.5815.12second4.7116.4873.8924.57third5.9812.6580.3224.33fourth8.855.4110043.17%rmsemg : % root mean square electromyography , mws : maximum walking speed ) .\nthe maximum walking speed gradually increased over the period from when the \n prosthesis was worn for the first time to when the subjects were discharged from the \n hospital ( table 2 ) .\nthe basic elements for the smoothest and most energy efficient walk are proper balance \n ability and posture control function2 . in \n lower limb amputation , the contralateral lower limb function influences subsequent ability \n to perform daily living and transfer activities , and standing balance on the unaffected side \n is an important determinant of whether walking with a prosthesis is possible or not3 .\nreported that the muscle of \n the unaffected lower limb of prosthesis wearers tended to adopt a balancing strategy to \n compensate for the loss of the ankle joint and muscles due to amputation4 .\ntherefore , lower limb amputees need to \n adapt to asymmetrical body weight and muscular strength when they exert effort to maintain \n static standing while wearing a prosthesis . in the present study , we evaluated the changes \n in surface emg activity of the gastrocnemius during standing , and the walking speed with a \n prosthesis .\nthe muscular activity of ga is most conspicuous when the amputee is standing \n with the prosthesis for the first time .\nwhen the static standing position is maintained , the \n ga is activated in preparation for the forward movement of the center of pressure5 , 6 .\nwe \n found two unique muscle activity patterns were exhibited by the two below - knee amputees . \n\nwhen the prosthesis was first worn , the younger subject was so careful about maintaining the \n standing posture that adequate forward movement of the center of gravity could not be \n achieved . for the elderly subject\n, however , marked activity of the ga was found , and ga \n activity at the final assessment was lower than that of the initial measurement , especially \n during the forward weight shift task .\nthese time - dependent changes in the muscular activity \n of ga indicate how younger and elderly amputees adapt muscular force to maintain standing \n posture , and it might also be as a cause of falls by elderly patients in the early stage of \n standing or gait training .\nthe subjects learned the method for shifting the center of gravity forward in a \n stable manner , resulting in the gradual reduction or increase of ga muscle activity .\nthere are many \n factors known to contribute to the improvement of the walking speed of amputees .\nas far as \n the results of this study are concerned , it can be concluded that one important factor is \n regaining the ability to be able to shift the center of gravity in the static standing \n position through the efficient muscle activity of the unaffected lower limb . in conclusion , \n the trend of muscle activities over time should contribute to the development of effective \n rehabilitation programs .\ndue to the limited number of subjects included in this study , a statistical analysis of \n sufficient power could not be performed .\nfurthermore , there were obvious differences in \n biomechanical , physiological , and psychological attributes because of age differences . \n\nbiomechanical or physiological perspective approaches are very important . in this study , \n however , there was no history of disorders of the trunk , such as lordosis or kyphosis , so we \n only focused on the differences in emg .\nfurther studies with larger numbers of subjects \n stratified by the causes and types of amputation are needed to clarify the specific factors \n associated with the acquisition of the ability to walk by amputees , and the development of \n efficient methods for physical therapy and programs .", "answer": "[ purpose ] dysfunction of lower extremity muscles is one risk factor of falls for amputee \n patients . \n however , the change in muscle activity pattern and balance ability of amputees \n who have no experience in standing with prosthesis during the period from prosthesis \n fitting to regaining the ability to walk has never been studied . \n therefore , the objectives \n of the present study were to elucidate changes over time in the muscle activity pattern \n and walking speed from first prosthesis fitting to hospital discharge . \n we also \n investigated the differences of muscle activity during standing between younger and \n elderly amputee patients . \n [ methods ] electromyography measurements were performed on the \n gastrocnemius of the intact leg during standing . \n the test subjects were asked to shift \n their center of gravity forward . \n [ results ] two unique patterns of gastrocnemius activities \n were observed over time . in a younger patient , \n the amount of muscular activity of the \n gastrocnemius gradually increased over time . in an elderly patient , however , the amount of \n muscular activity of gastrocnemius gradually decreased over time . \n [ conclusion ] the \n time - dependent changes in gastrocnemius muscle activities are indicative postural control \n ability . \n therefore , understanding the time - dependent changes in muscle activities during \n rehabilitation and the differences of postural control between younger and elderly \n patients would contribute to the development of effective rehabilitation programs for each \n patient .", "id": 771} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nacute embolic limb ischemia is an urgent clinical condition in which sudden decrease or worsening in limb perfusion causes a potential threat to extremity viability and to life .\nthorough removal of all occlusive emboli in the arterial tree results in the best outcomes ; hence , some authors favored arteriography after embolectomy for lower limbs . \n \nangiography is traditionally performed with iodinated contrast material , but carbon dioxide ( co2 ) has been studied as an alternative intravascular contrast agent for patients with iodine allergy or renal function impairment .\nsince it is not nephrotoxic , it was considered reasonable to utilize this contrast in a patient with borderline renal function who would be submitted to the noxious stimuli of the reperfused limb after revascularization . \n to the best of our knowledge ,\nthis was the first case assessing the intraoperative use of co2 as a substitute for iodine contrast in a patient with known chronic kidney disease and an acute ischemic limb .\na 79-year - old woman presented to the emergency department with acute limb ischemia in her left leg with a 2-hour history .\npast medical history was positive for hypertension , atrial fibrillation and non - dialysis - dependent chronic renal failure .\ntwo years before , she had been operated on for acute aortic embolic occlusion , with bilateral femoral catheter embolectomy .\nupon discharge she presented pedal pulses , but no posterior tibial pulses on either limb .\nmedication use was irregular , and her international normalized ratio ( inr ) of prothrombin time upon admission was 1.1 .\nher pulse was arrhythmic ; she was hypertensive ( 160x110mmhg ) and presented with normal femoral , popliteal and pedal pulses on her right leg .\non palpation in the left lower limb only a weak femoral pulse was observed ; there were no distal pulses .\nshe was classified as grade iib limb ischemia ( immediately threatened ) and was immediately referred for surgery .\npreoperative exams revealed a diminished creatinine clearance ( cockroft - gault of 12ml / min ) .\narteriotomy was performed and a 4-fr embolectomy catheter was utilized ( edwards lifesciences corp , irvine , california , usa ) .\nthe catheter progressed more than 60 cm on the superficial artery , but could not be felt neither on pedal artery topography nor on posterior tibial artery topography .\nback bleeding was not significant , and a decision was made to perform an angiography to better assess the infra - popliteal arterial tree .\na homemade water seal co2 delivery system was used , similar to another previously described , but with one modification to prevent room - air contamination .\nbloomington , indianopolis , usa ) inserted in the arteriotomy while the arteries were clamped . \n\nfigure 1 shows a patent popliteal artery , a patent fibular artery and an occlusion on the mid - third of the anterior tibial artery .\nwe hypothesized that the embolectomy catheter reached the fibular artery on the first attempt , and thus could not be felt on physical exam . \n\npatent popliteal and fibular arteries , occlusion in the mid - third of the anterior tibial artery \n a new embolectomy was then performed .\nthe catheter progressed to the foot , on the topography of the pedal artery ( i.e. , the catheter could be felt on the projection of the artery ) , and more thrombi were retrieved .\ncontrol angiography ( figure 2 ) showed complete resolution of the anterior tibial artery occlusion , with contrast up to the foot ( figure 3 ) .\na total of 28ml of co2 was used , and no iodine contrast was needed . \n\nthe arteries were unclamped , and the popliteal and pedal pulses were noted to be present on the limb .\nischemia signs ( e.g. , pallor , hypothermia ) were promptly resolved after arterial flow release .\nthe patient remained in the intensive care unit ( icu ) until the 11 postoperative day . during this period ,\nthe patient did not receive any nephrotoxic agent , such as vancomycin or vasoactive drugs .\nafter icu discharge she developed a urinary tract infection , as well as deteriorating renal function and uremia .\nthe patient developed pneumonia , which progressed to septic shock on the 36 day of her admission .\nshe required vasoactive drugs for 2 days at the icu and , unfortunately , her renal function was never fully recovered .\nshe was discharged from hospital to a hospice care facility with a pedal pulse and no deficit on her limb , though requiring chronic dialysis .\ntreatment of embolic arterial occlusion with severe limb ischemia is well defined and involves the use of an embolectomy catheter as the best alternative . \n \nco2 has been used electively in both diagnostic and therapeutic procedures in the femoropopliteal tree , and is reported to be safe and non - nephrotoxic . \n \nintraoperative angiography was beneficial because it allowed the diagnosis of the arterial tree occlusion after the initial embolectomy .\nadditional removal of clots was performed and the result was documented as complete patency of the anterior tibial artery to the foot .\nour goal , when using co2 , was to decrease the need for postoperative dialysis .\nprobably , in this case , the deleterious stimuli ( surgical stress , urinary tract infection and septic shock due to pneumonia ) contributed to renal failure and subsequent need for dialysis . the countermeasure ( such as the use of non - nephrotoxic contrast )\nif we had used the iodinated medium , we might wonder if something could have been done differently to avoid dialysis .\nwe consider co2 to be an alternative to iodine contrast when the decision to perform angiography is made in the acutely ischemic limb . to the best of our knowledge\n, this agent has never been described in this clinical setting ; it presents good quality imaging , is not nephrotoxic and does not increase the risk for the limb or the patient in acute arterial occlusions .\nthis approach may prove to be fruitful in patients with borderline renal function , thereby reducing the risk of short or long - term need for dialysis .\na isquemia aguda de membro de origem emblica uma situao clnica de carter urgente , em que ocorre uma diminuio ou piora sbita na perfuso de um membro , e configura um risco viabilidade da extremidade e vida .\no tratamento consiste em revascularizao imediata com um cateter de embolectomia . a remoo completa de todos os mbolos oclusivos na rvore arterial leva aos melhores desfechos ; por isso\n, alguns autores defendem a arteriografia aps a embolectomia , para os membros inferiores . \n a angiografia tradicionalmente realizada com contraste iodado , mas o dixido de carbono ( co2 ) foi estudado como um agente de contraste intravascular alternativo para pacientes com alergia a iodo ou alterao na funo renal .\ncomo o co2 no nefrotxico , julgou - se razovel utilizar esse contraste em uma paciente com funo renal limtrofe ( borderline ) que seria submetida aos estmulos nocivos de reperfuso do membro , aps a revascularizao . \n \nem nosso entender , este foi o primeiro caso que avalia o uso intraoperatrio de co2 como um substituto de contraste iodado em um paciente com doena renal crnica conhecida e isquemia aguda de membro .\npaciente do sexo feminino , 79 anos , chegou ao pronto - socorro com isquemia aguda no membro inferior esquerdo , com durao de 2 horas .\ncomo antecedentes , apresentava hipertenso , fibrilao atrial e insuficincia renal crnica , no dependente de dilise .\na paciente tinha sido operada 2 anos antes , por ocluso artica aguda de origem emblica , quando foi realizada embolectomia femoral bilateral com cateter .\n alta , os pulsos pediosos eram palpveis , mas os tibiais posteriores eram ausentes , bilateralmente .\na paciente fazia uso irregular dos medicamentos , e o tempo de protrombina ( inr , sigla do ingls international normalized ratio ) era de 1,1 . o pulso estava arrtmico ; era hipertensa ( 160x110mmhg ) e apresentava pulsos femoral , poplteo e distal normais , na perna direita .\n palpao do membro inferior esquerdo , havia apenas um pulso femoral fraco ; os pulsos distais estavam ausentes . a paciente apresentava dor e dfice motor .\nela foi considerada como portadora de isquemia de membro grau iib ( risco eminente ) e foi encaminhada imediatamente para cirurgia .\no clearance de creatinina estava diminudo nos exames pr - operatrios ( cockroft - gault de 12ml / min ) .\nsob anestesia geral , foi realizado acesso femoral na cicatriz da inciso anterior do membro inferior esquerdo . as artrias femorais comum , superficial e profunda foram dissecadas e clampeadas .\nfoi feita arteriotomia e uso de cateter de embolectomia de 4fr ( edwards lifesciences corp , irvine , califrnia , estados unidos ) .\nos trombos foram removidos das artrias femorais superficial e profunda . o cateter avanou mais de 60 cm na artria femoral superficial , mas no pde ser palpado . o fluxo retrgrado no foi significativo e decidiu - se realizar uma angiografia para avaliar melhor a rvore arterial infrapopltea .\nfoi escolhido o co2 como substituto ao contraste iodado para a angiografia . utilizou - se um sistema home - made com fornecimento de co2 em selo dgua , semelhante a outro descrito anteriormente , mas com uma modificao para evitar a contaminao do ar ambiente .\nbloomington , indianpolis , estados unidos ) inserido na arteriotomia , quando as artrias foram pinadas .\na figura 1 mostra uma artria popltea e uma fibular prvias , e uma ocluso no tero mdio da artria tibial anterior .\nlevantamos a hiptese de o cateter de embolectomia ter alcanado a artria fibular na primeira tentativa , e por isso no ter sido palpvel ao exame fsico . \n\nartrias popltea e fibular prvias , ocluso no tero mdio da artria tibial anterior \n realizou - se , ento , nova embolectomia .\no cateter avanou at o p , na topografia da artria pediosa ( isto , o cateter pde ser palpado na projeo da artria ) e mais trombos foram removidos . a angiografia de\ncontrole ( figura 2 ) mostrou resoluo completa da ocluso da artria tibial anterior , com contraste fluindo at o p ( figura 3 ) .\nforam usados 28ml de co2 , e no foi necessrio aplicar o contraste iodado . \n\nresoluo completa da ocluso da artria tibial anterior \n \n figura 3arteriografia com dixido de carbono .\nchegada de contraste na artria tibial anterior at o p \n foi realizada a arteriorrafia . as artrias foram desclampeadas ,\nos sinais de isquemia ( palidez e hipotermia ) foram imediatamente resolvidos aps a liberao do fluxo arterial .\na paciente no desenvolveu sinais de sndrome compartimental . a paciente permaneceu na unidade de terapia intensiva ( uti ) at o 11 dia ps - operatrio .\ndurante esse perodo , no recebeu nenhum agente nefrotxico , como vancomicina ou drogas vasoativas .\naps a alta da uti , desenvolveu infeco urinria , piora da funo renal e uremia .\niniciou dilise no 18 dia ps - operatrio . a paciente teve pneumonia , que evoluiu para choque sptico no 36 dia de internao .\nnecessitou de drogas vasoativas por 2 dias na uti e , infelizmente , nunca mais recuperou a funo renal .\nteve alta hospitalar e foi para instituio de cuidados terminais , com pulso distal sem dfice no membro inferior , mas em dilise crnica .\no tratamento da ocluso arterial emblica com isquemia grave de membro est bem definido , sendo o uso de cateter de embolectomia a melhor alternativa . \n \no co2 tem sido empregado de forma eletiva tanto nos procedimentos diagnsticos como nos teraputicos na rvore fmoro - popltea , sendo descrito como seguro e no nefrotxico . \n a angiografia intraoperatria foi benfica , j que permitiu o diagnstico de ocluso da rvore arterial aps a primeira embolectomia . mais cogulos foram removidos , e o resultado documentado foi a permeabilidade completa da artria tibial anterior at o p .\nnosso objetivo , ao utilizar co2 , foi o de diminuir a necessidade de dilise no ps - operatrio .\nneste caso , provavelmente , os estmulos prejudiciais ( estresse cirrgico , infeco do trato urinrio e choque sptico por pneumonia ) contriburam para a insuficincia renal e para consequente necessidade de dilise . a contramedida ( como o uso de contraste no nefrotxico ) poderia ter prevenido a insuficincia renal , se fosse esta uma situao nica .\nse tivssemos usado o contraste iodado , pensaramos se algo diferente poderia ter sido feito para evitar dilise .\nconsideramos o co2 como uma alternativa ao contraste iodado quando necessria a angiografia para isquemia aguda de membro .\nem nosso entender , esse agente nunca foi descrito nessa situao clnica , proporcionando boa qualidade de imagem , no sendo nefrotxico , nem aumentado o risco do membro ou do paciente , em casos de ocluses arteriais agudas .\nessa abordagem pode se mostrar til em pacientes com funo renal limtrofe ( borderline ) , reduzindo , assim , o risco de precisar de dilise a curto ou longo prazo .", "answer": "acute limb ischemia can be potentially harmful to the limb and life threatening . \n renal failure is a possible outcome associated with release of products of ischemic limb reperfusion . \n some authors reported the benefit of performing angiography after embolectomy , even though iodine contrast is also nephrotoxic . \n we report a case of embolectomy on a patient with renal insufficiency in whom carbon dioxide was used as a substitute for iodine contrast .", "id": 772} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary ovarian cancers tend to spread , at first , within the peritoneal cavity and the omentum , and are frequently associated with ascites , a fluid rich in growth factors and tumor cells disseminated from the primary cancer that fills the peritoneum .\ntumor spread to more distant sites , including the contralateral ovary and bilateral ovarian cancers almost always represents a primary tumor and its metastasis rather than dual primary cancers .\nthe parallel evolution model suggests that cells with metastatic potential separate from the primary tumor at an early stage in development and evolve independently from the primary tumor .\nthe ovary is a site for a wide range of tumors , both primary and metastatic .\ncolorectal metastasis from primary ovarian carcinoma account for approximately 4.0% and an isolated rectal metastasis is very rare .\nidentification of the correct primary tumor is necessary for an optimal management , including , specific chemotherapy ( ct ) in advanced stages . whereas , ovarian adenocarcinomas respond to platinum based ct , cases of colonic adenocarcinomas are candidates for 5-fluorourocil based ct .\na 50-year - old female patient presented with bilateral adnexal lump and dysfunctional uterine bleeding with altered bowel habits . computed tomography of the abdomen and pelvis revealed a bilateral adnexal lump situated in the ovaries of sizes 108 cm and 43 cm , and a lobular mass of 8 cm at the rectum with peritoneal implants ( figure 1 ) .\nshe underwent a total hysterectomy , a bilateral adnexectomy , and a bilateral iliac lymphadenectomy for the bilateral ovarian lumps .\ngross features of the ovaries showed capsular breach with presence of solid and cystic areas on cut sections .\nthe microscopic examination revealed a bilateral papillary serous adenocarcinoma with psammomatous calcification ( figure 2 ) .\nthe surgical findings revealed an 8.0 cm submucosal tumor in the rectum and invasion from the serosal side .\nthe tumor primarily involved the rectal muscularis propria and subserosa with only focal invasion of the rectal mucosa .\nthe pathological findings of the ovarian tumor specimen were consistent with those of the hemicolectomy specimen .\nthe patient was staged as t3cn1m1 and stage iv , according to tnm and figo classification respectively . \n\nfigure 1computed tomography of the abdomen revealed a bilateral adnexal lump situated in both the ovaries with peritoneal implants . \n computed tomography of the abdomen revealed a bilateral adnexal lump situated in both the ovaries with peritoneal implants . \n\nfigure 2carcinoma ovary shows papillary serous adenocarcinoma with psammomatous calcification ( hematoxylin & eosin 40 ) . \n \ncarcinoma ovary shows papillary serous adenocarcinoma with psammomatous calcification ( hematoxylin & eosin 40 ) . \n\nfigure 3colorectal carcinoma shows moderately differentiated adenocarcinoma ( hematoxylin & eosin 40 ) . \n colorectal carcinoma shows moderately differentiated adenocarcinoma ( hematoxylin & eosin 40 ) .\nimmunohistochemical staining was positive for cytokeratin 7 ( figure 4 ) and negative for cytokeratin 20 ( figure 5 ) .\nthis staining pattern was consistent with that of colorectal metastasis from the original ovarian lesion and immunohistochemistry supported the histological interpretation of a metastatic ovarian carcinoma .\npost adjuvant 6 cycles of specific ct in the form of cisplatinum ( 50 mg ) and 5-fluorourocil ( 100 mg ) were administered to our patient and after 6 months of follow up period , she is doing well . \n\nfigure 4positive immunohistochemical staining for cytokeratin 7 ( immunostain cytokeratin 7 40 ) . \n \nfigure 5negative immunohistochemical staining for cytokeratin 20 ( immunostain cytokeratin 20 40 ) . \n \nharaoka et al . in an autopsy series , reported that colorectal metastases present with an ovarian origin in about 6.0% of cases and represent about 30.5% of all ovarian cancers .\ntheir patients ranged in age from 34 to 77 years with an average age of 58.8 years .\nthe location was ascending colon in 4 patients , transverse in 2 , descending in 5 , sigmoid in 5 , and rectum in 5 .\nthe tumor appearance was protruding in 13 cases , ulcerative in 2 , and a submucosal tumor type in 1 of the 14 cases in which the macroscopic appearance was reported . in 9 of the 14 cases in which the tumor protruded\n, distinguishing colorectal metastasis from ovarian carcinoma and primary colon cancer based on the macroscopic appearance is often difficult .\ncolorectal metastasis was observed to be synchronous with ovarian carcinoma in 7 patients in a study by loy et al . ,\n, elevated levels of tumor markers such as ca-125 and cea may help to make a correct diagnosis .\nhowever , up to 15% of the cases of ovarian carcinoma were present without any elevated levels of serum ca-125 .\nreported a cytokeratin 7 positive / cytokeratin 20 negative immunophenotype to be nearly 100% specific for an ovarian origin .\nconversely , a cytokeratin 7 negative/ cytokeratin 20 positive immunophenotype was seen in 94% of the tumors of colonic origin . in our case ,\nthe colonic tumor was positive for cytokeratin 7 and negative for cytokeratin 20 , a pattern consistent with an ovarian origin rather than a colonic one .\nin addition , a comparison of the patient 's primary ovarian cancer with the colorectal mass revealed that the two tumors have similar histological features .\nthe spread of ovarian cancer to the colorectum can occur in four different ways , hematogenous spread , lymphatic spread , direct invasion and peritoneal dissemination .\nthe most plausible explanation of colorectal involvement in ovarian adenocarcinomas is through intra - peritoneal seedling .\nhematogenous spread occurs in advanced peritoneal disease . in a substantial number of autopsy cases of advanced ovarian cancers , reed et al .\nidentified peritoneal involvement in 83100% cases , with large intestinal involvement in 5060% cases . in most cases of bowel metastases ,\nthe serosa is affected initially and then invasion extends from serosal and subserosal tissues into the muscularis propria and mucosa of the bowel wall . in the present case , the tumor mainly involved the rectal muscularis propria and subserosa with only focal invasion of the rectal mucosa and invasion of the retroperitoneum .\ncertain morphological features indicative of metastasis from colorectum include garland - like tumor necrosis , segmental destruction of glands and absence of squamous metaplasia , whereas cribriform growth patterns and intra - luminal dirty necrosis are indicators of ovarian adenocarcinomas .\nhowever , the problem exists in sorting out these tumors , including in cases mucinous adenocarcinomas , when there is simultaneous involvement of the ovary and the colorectum at similar ( synchronous ) or at different ( metachronous ) times .\nshowed that morphologically , metastatic tumor deposits in the colorectum retained the morphology of ovarian papillary serous cystadeocarcinoma with foci of psammomatous calcification in 6 of their 11 cases .\nabsence of garland - like tumor and necrosis were pointers towards an ovarian primary , apart from the clinical context of a preceding ovarian tumor in 81.8% such cases .\nit is thus important to identify whether or not a tumor has an ovarian origin using immunohistochemical markers , since the occurrence of gastrointestinal metastases from ovarian cancer is very rare .\nas described lately , specific cytokeratin immunemarkers like cytokeratin 7 and cytokeratin 20 have been documented to be helpful in resolving these dilemmatic situations of ovarian involvement by colorectal carcinoma and vice versa .\nzighelboim et al . described a single case of atypical sigmoid metastasis from a high - grade ovarian adenocarcinoma , using differential expression of ck7 and 20 .\no'hanlan et al . have reported that a longitudinal negative margin of 25 cm in the resected bowel along with a wedge resection of mesentery , including paracolic and intermediate - level nodes might be indicated to achieve optimal debulking of gastrointestinal metastases from ovarian carcinomas .\nour patient underwent total hysterectomy , bilateral adnexectomy , and bilateral iliac lymphadenectomy with left hemicolectomy and postoperative chemotherapy .\nin cases of colorectal involvement by ovarian adenocarcinomas and vice versa , it can be difficult to ascertain an exact primary .\nin such cases , apart from complete clinical details , histomorphological features like garland - like necrosis , desmoplasia and psammomatous calcification are useful pointers towards exact primary and along with differential expression of cytokeratins 7 and 20 by immunohistochemistry can be helpful in solving these dilemmas .", "answer": "this report describes the case of a 50-year - old female patient who presented with bilateral adnexal lump and dysfunctional uterine bleeding with altered bowel habits . \n computed tomography of the abdomen and pelvis revealed a bilateral adnexal lump situated in both the ovaries and a lobular mass of 8 cm in the rectum . \n proctoscopy revealed an elevated irregular rectal lesion . \n the microscopic examination of the ovarian lump revealed a bilateral serous adenocarcinoma with a papillary pattern with psammomatous calcification . \n a left hemicolectomy with lymphadenectomy was also performed . \n immunohistochemical staining was positive for cytokeratin 7 and negative for cytokeratin 20 . \n the use of immunohistochemistry demonstrated the tumor to be of ovarian origin . \n we report this case of synchronous involvement of the ovary and the colorectum because of its rarity and unusual presentation .", "id": 773} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbecause motor weakness is one of the most serious disabling sequelae of stroke , so it is important to elucidate the motor recovery mechanism for successful rehabilitation .\nmany studies have attempted to elucidate the motor recovery mechanism of stroke and several motor recovery mechanisms have been suggested .\nhowever , the majority of these studies focus on cerebral infarct and relatively little is known about the motor recovery mechanism of intracerebral hemorrhage ( ich ) .\ndiffusion tensor imaging ( dti ) can help to investigate the motor recovery mechanism of ich by enabling the direct visualization and estimation of the corticospinal tract ( cst ) .\n, we report on a patient with ich who showed a change in the origin of an injured cst from the premotor cortex ( pmc ) to the primary motor cortex ( m1 ) .\nan 86-year - old woman presented with complete paralysis of the right upper and lower extremities , which occurred at the onset of spontaneous ich ( motricity index ( mi ) : 0 ( full mark : 100 ) ) ( table 1 ) .\nlongitudinal changes in motor function t2-weighted mr images showed a hematoma in the left fronto - parietal lobe , including m1 , at 1 month after onset , that resolved at 5 months after onset ( figure 1a ) . from 1 month to 5 months after onset , she received comprehensive rehabilitative management , which included the administration of neurotrophic drugs ( ropinirole , bromocriptine , levodopa , and amantadine ) , movement therapy , and neuromuscular electrical stimulation of the affected finger extensors and ankle dorsiflexors .\nmovement therapy focused on improving the motor functions of the right upper and lower extremities and included physical and occupational therapy sessions five times per week .\nweakness of her left extremities improved from an mi score of 0 point at 1 month to 27 points at 2 months and to 52 points ( 5 months after ich onset ) after 4 months of rehabilitation . as a result\n, she was able to extend the affected fingers against gravity and to walk independently on even ground .\nbrain magnetic resonance images , diffusion tensor imaging ( dti ) and transcranial magnetic stimulation results of an 86-year - old female patient with a hematoma in the left fronto - parietal lobe .\n( a ) t2-weighted magnetic resonance images showed a hematoma in the left fronto - parietal lobe including the primary motor cortex at 1 month after onset , which was resolved at 5 months after onset .\ndti results showed that at 1month and 5 months after intracerebral hemorrhage , the right csts originated from the cerebral cortex , including the primary motor cortex , and then passed through the known cst pathway . in the left ( affected ) hemisphere\n, the csts originated from the left premotor cortex at 1 month after onset , and from the left primary motor cortex and premotor cortex at 5 months after onset .\na motor evoked potential of low amplitude ( 100 v ) was obtained from right abductor pollicis brevis muscle by the affected ( left ) hemisphere stimulation at 1 month after onset . however , motor evoked potential amplitude was increased to the normal range ( 3.8 mv ) at 5 months after onset .\nich volume was measured on ct image and t2-weighted mri images through picture archived communication system ( pacs , marotech , korea ) .\nthe maximum width ( x ) , length ( y ) and height ( z ) of lesion at the level where a hematoma was clearly seen were measured .\nthe ich volume was calculated according to the formula : the volume of ich was 37.19 mv on the ct images at the ich onset and 26.71 mv on the mr images at 1 month after onset .\ndiffusion tensor images were acquired using a synergy - l sensitivity encoding ( sense ) head coil on a 1.5-t philips gyroscan intera system ( hoffman - laroche , mijdrecht , the netherlands ) using a single - shot echo planar imaging with a navigator echo .\nfor each of the 32 noncollinear diffusion - sensitizing gradients , 60 contiguous slices ( matrix = 192 192 , field of vision = 240 mm , repetition time / echo time = 10 726/76 ms , b = 600 mm / s , number of excitations = 1 , thickness = 2.5 mm ) were acquired .\nthree - dimensional reconstructions of fiber tracts were obtained using the dti task card software ( philips extended mr work space 2.6.3 ) ( threshold fractional anisotropy ( fa ) = 0.15 , angle = 45 ) .\nfiber tracts passing through both region of interests ( cst portion of the anterior mid - pons and low - pons on the color map ) were designated final tracts of interest . at 1 month and 5 months after ich onset , dti results showed that in the right ( non - affected ) hemisphere , the right cst originated from the cerebral cortex ( including m1 ) and passed through the known cst pathway .\nhowever , in the left ( affected ) hemisphere , the cst originated from the left pmc at 1 month and from the left m1 and pmc at 5 months ( figure 1b ) .\ntms was performed using a magstim novametrix 200 magnetic stimulator equipped with a 9-cm mean diameter circular coil ( novametrix medical systems inc , wallingford , ct , usa ) .\nthe left hemisphere was stimulated by a counterclockwise current and the right hemisphere was stimulated by a clockwise current .\nmotor - evoked potentials ( meps ) were obtained from both abductor pollicis brevis muscles in a relaxed state . excitatory threshold ( et )\nwas defined as the minimum stimulus required to elicit an mep with a peak - to - peak amplitude of 50 v or greater during two of four attempts .\neach site was stimulated three times with inter - stimulus intervals of 10 seconds , and shortest latency and average peak to peak amplitude were estimated .\nmep ( latency : 23.5 ms ; amplitude : 100 v ; et : 100% ) was evoked from the affected ( left ) hemisphere during the tms study conducted at 1 month after ich onset , but the amplitude increased to the normal range at 5 months after ich onset ( latency : 19.7 ms ; amplitude : 3.8 mv ; et : 70% ) ( figure 1c ) .\nich volume was measured on ct image and t2-weighted mri images through picture archived communication system ( pacs , marotech , korea ) . the maximum width ( x ) ,\nlength ( y ) and height ( z ) of lesion at the level where a hematoma was clearly seen were measured .\nthe ich volume was calculated according to the formula : the volume of ich was 37.19 mv on the ct images at the ich onset and 26.71 mv on the mr images at 1 month after onset .\ndiffusion tensor images were acquired using a synergy - l sensitivity encoding ( sense ) head coil on a 1.5-t philips gyroscan intera system ( hoffman - laroche , mijdrecht , the netherlands ) using a single - shot echo planar imaging with a navigator echo .\nfor each of the 32 noncollinear diffusion - sensitizing gradients , 60 contiguous slices ( matrix = 192 192 , field of vision = 240 mm , repetition time / echo time = 10 726/76 ms , b = 600 mm / s , number of excitations = 1 , thickness = 2.5 mm ) were acquired .\nthree - dimensional reconstructions of fiber tracts were obtained using the dti task card software ( philips extended mr work space 2.6.3 ) ( threshold fractional anisotropy ( fa ) = 0.15 , angle = 45 ) .\nfiber tracts passing through both region of interests ( cst portion of the anterior mid - pons and low - pons on the color map ) were designated final tracts of interest . at 1 month and 5 months after ich onset , dti results showed that in the right ( non - affected ) hemisphere , the right cst originated from the cerebral cortex ( including m1 ) and passed through the known cst pathway .\nhowever , in the left ( affected ) hemisphere , the cst originated from the left pmc at 1 month and from the left m1 and pmc at 5 months ( figure 1b ) .\ntms was performed using a magstim novametrix 200 magnetic stimulator equipped with a 9-cm mean diameter circular coil ( novametrix medical systems inc , wallingford , ct , usa ) .\nthe left hemisphere was stimulated by a counterclockwise current and the right hemisphere was stimulated by a clockwise current .\nmotor - evoked potentials ( meps ) were obtained from both abductor pollicis brevis muscles in a relaxed state . excitatory threshold ( et )\nwas defined as the minimum stimulus required to elicit an mep with a peak - to - peak amplitude of 50 v or greater during two of four attempts .\neach site was stimulated three times with inter - stimulus intervals of 10 seconds , and shortest latency and average peak to peak amplitude were estimated .\nmep ( latency : 23.5 ms ; amplitude : 100 v ; et : 100% ) was evoked from the affected ( left ) hemisphere during the tms study conducted at 1 month after ich onset , but the amplitude increased to the normal range at 5 months after ich onset ( latency : 19.7 ms ; amplitude : 3.8 mv ; et : 70% ) ( figure 1c ) .\nin this patient , we investigated changes of the injured left cst and found that the injured cst seemed to recover as detected by dti , tms and clinical observation . at 1 month after ich onset , the left cst originated from the pmc by dti , and the mep obtained at the right hand showed low amplitude and a latency compatible with that of the cst .\nby contrast , 5-month results revealed that the left cst originated from the left m1 by dti and that mep amplitude had improved to the normal range by tms .\nthe m1 is the major origin of the cst , although the cst is known to originate from the extensive cerebral cortex , including the pmc , the primary somatosensory cortex , and the prefrontal cortex . on the other hand ,\nconsequently , the dti and tms results of this patient suggest that the severely injured left cst had recovered over 4 months in terms of its origin and fiber number .\nfurthermore , clinically , the finding that the patient was able to flex and extend against gravity at 5 months after ich onset provides additional evidence of left cst recovery . as a result\n, right extremity motor functions seemed to have been recovered due to reorganization of the injured left cst originating from the left pmc to left m1 .\nit is also possible that compression of the cst into the left pmc recovered in concert with hematoma resolution . for the motor recovery mechanism in ich ,\nseveral dti based studies have described recovery of an injured cst or the contribution made to recovery by the contralateral unaffected cst . during the last 5 years\n, a number of serial dti studies have described the recovery of injured cst after ich .\njang et al demonstrated the recovery process of an injured cst in a patient with a subcortical ich by serial dti .\nthe patient presented with complete paralysis of right extremities at onset , but over 16 months , motor functions of affected extremities slowly recovered to nearly normal .\nfurthermore , dtt showed that the origin of the cst had changed from the posterior parietal cortex at 1 month to the primary somatosensory cortex at 4 months and m1 at 16 months .\nthe authors suggested that recovery of the origin of the damaged cst was due to a process of normalization from the parietal cortex to m1 .\nby contrast , our patient showed a change in the origin of the injured cst from the pmc to m1 .\nthis study described changes of an injured cst that occurred in concert with motor recovery in a patient with ich . to the best of our knowledge ,\nthis is the first longitudinal study to demonstrate a change in the origin of an injured cst from the pmc to m1 in ich .\nresults from this study suggest a motor recovery mechanism of ich and the important implications regarding brain plasticity and brain rehabilitation after ich .\nhowever , this study is obviously limited by case numbers , and further complementary studies involving larger case numbers are warranted .", "answer": "many studies have attempted to elucidate the motor recovery mechanism of stroke , but the majority of these studies focus on cerebral infarct and relatively little is known about the motor recovery mechanism of intracerebral hemorrhage . in this study , we report on a patient with intracerebral hemorrhage who displayed a change in injured corticospinal tract originating from the premotor cortex to the primary motor cortex on diffusion tensor imaging . an 86-year - old woman presented with complete paralysis of the right extremities following spontaneous intracerebral hemorrhage in the left frontoparietal cortex . \n the patient showed motor recovery , to the extent of being able to extend affected fingers against gravity and to walk independently on even ground at 5 months after onset . \n diffusion tensor imaging showed that the left corticospinal tract originated from the premotor cortex at 1 month after intracerebral hemorrhage and from the left primary motor cortex and premotor cortex at 5 months after intracerebral hemorrhage . \n the change of injured corticospinal tract originating from the premotor cortex to the primary motor cortex suggests motor recovery of intracerebral hemorrhage .", "id": 774} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlaparoscopic ventral incisional hernia ( vih ) repair has gained wide acceptance and increased popularity over the past decade .\nmultiple studies have documented the safety , technical feasibility , and efficacy of this technique .\nthe extremely low rate of wound infection and recurrence are among the most important advantages of the laparoscopic approach .\nbecause the prosthetic mesh is placed intraabdominally , many surgeons use expanded polytetrafluoroethylene ( eptfe ) grafts because of the low adhesive potential . , , high cost , inferior handling characteristics , and poor incorporation into the tissues are among the drawbacks of eptfe mesh . another product , polypropylene ( pp )\nnevertheless , long - term complications , such as severe adhesions , obstruction , and fistula formation , have been reported with pp . , these complications seem to occur when the pp mesh is placed in direct contact with the serosal surface of the bowel . however , if omentum is interposed between the mesh and viscera , adhesions should not involve loops of bowel and should be restricted to omentum only . using this technique , franklin\net al reported no adhesion - related complications in over 170 patients undergoing laparoscopic vih repair during a 30-month follow - up .\nbetween 1999 and 2001 , patients undergoing laparoscopic vih repair were prospectively enrolled in a surgical database . in 30 patients , pp mesh ( prolene , ethicon corporation , somerville , nj )\nwas used for the hernia repair ; omentum was interposed between the mesh and the underlying bowel .\nthe mesh was secured in place with a hernia stapler along the edges and nonabsorbable transcutaneous sutures at the corners , taking care to ensure that the mesh overlapped the fascial defect by at least 3 cm in each direction . at a mean follow - up of 14 months\ntwenty patients agreed and were studied using an acuson xp/10 , 7 mhz linear transducer , supplemented by a curvilinear transducer when appropriate .\na visceral slide technique was used specifically to detect adhesions . at the time of follow - up , all patients were also examined for hernia recurrence , wound infection , and seroma formation .\nsatisfaction with the procedure ( completely / somewhat / not satisfied ) and pain at the operative site ( mild / moderate / severe ) were assessed by using a standard questionnaire .\nthis method is based on the demonstration of intestinal movement at the abdominal wall interface during real - time ultrasound imaging .\nsuch movement may occur spontaneously as a result of respiratory excursions or may be induced by manual compression . during longitudinal surface scanning ,\na normal spontaneous visceral slide may range from 2 cm to more than 5 cm in distance .\ndetection of a visceral slide that measures less than 1 cm is considered abnormal due to adhesions .\nthis method is based on the demonstration of intestinal movement at the abdominal wall interface during real - time ultrasound imaging .\nsuch movement may occur spontaneously as a result of respiratory excursions or may be induced by manual compression . during longitudinal surface scanning ,\na normal spontaneous visceral slide may range from 2 cm to more than 5 cm in distance .\ndetection of a visceral slide that measures less than 1 cm is considered abnormal due to adhesions .\nno detectable omental or bowel adhesions were found in more than half of the patients ( figure 1 ) . in some cases , mesh appeared to be somewhat corrugated , but normal visceral slide was detected in each instance ( figure 2 ) .\nfive patients had omentum that appeared to be densely adherent to the pp mesh , as detected by the lack of a normal visceral slide . in one of these patients ,\nthe bowel was visibly tethered underneath the omentum but was not adherent to the mesh .\none patient had tethered bowel at the edge of the hernia repair with thickened omentum underlying the mesh . in another patient ,\nthe falci - form ligament had been divided to complete the hernia repair in that case .\nthe incidence of adhesions ( % ) detected by ultra - sonography in 20 patents after laparoscopic ventral incisional hernia repair with polypropylene mesh and omental interposition .\nultrasonogram of the patient after laparoscopic ventral incisional hernia repair : mesh ( arrow ) appears to be corrugated .\nnine patients had no pain at the surgery site , while 10 patients stated they experienced mild to moderate pain with activity , usually near the edges of the repair ( figure 3 ) . only 2 patients complained of severe pain at the site of repair .\none of these patients described severe pain with activity even though she had been pain - free for 1 year after surgery .\nthis patient was noted to have a small recurrence of the hernia just lateral to the edge of the mesh ( figure 4 ) .\nher initial repair 3 years earlier was accomplished using the separation of components technique , which led to a subsequent recurrence .\nultrasonogram of the patient with the recurrent hernia : omental herniation ( thick arrow ) is seen just lateral to the mesh ( thin arrow ) .\nthe reasons for less than complete satisfaction include unexpected postoperative pain in 1 patient and moderate crampy postoperative pain in a second patient .\none patient had problems with a trocar site , and another patient felt that an area of attenuated fascia with underlying mesh constituted a recurrence .\nthe use of prosthetic materials for the repair of a ventral incisional hernia has significantly decreased the number of recurrences for this condition . moreover ,\nthe laparoscopic approach has helped to reduce the number of infections , recurrences , and the length of hospital stay .\nthe formation of adhesions has been studied in numerous experimental models . in 1 such study , increasing adhesion development was noted from day 1 to day 7 after placement of the prosthesis , but surfaces that were already covered with mesothelial cells did not show progression .\nthereafter , the bowel had a diminished tendency to form adhesions even in the absence of omentum .\nanother animal model was used to compare adhesion formation after open and laparoscopic placement of mesh .\nthe study demonstrated that the area of mesh covered with adhesions and the grade of the adhesions were significantly greater in both groups undergoing celiotomy compared with the adhesion formation in the laparoscopic group . on histologic examination\n, the vascularity of the animals that underwent incision through skin and fascia was increased and slower to regress than in the laparoscopically treated animals . in the clinical setting , pp mesh has been used previously for open vih repair with a very low rate of enterocutaneous fistula formation , but fistulas have been reported as late as 15 years after the procedure . in laparoscopic vih repair , pp has been combined with omental interposition as protection against bowel adhesions .\ncolocutaneous fistula after laparoscopic vih hernia repair with intraperitoneal ptfe has also been reported ; in this case , the laparoscopic staples or external postoperative trauma may have played a role .\nultrasound was used to detect adhesion formation at a time when this process was complete .\nvisceral slide detection by ultrasound was described by kodama et al in 1992 and was again validated in a french study with intraoperative observation and was noted to have a sensitivity of 77% , specificity of 74% , and a negative predictive value of 84% .\nthe data in our study were prospectively collected , but the overall number of patients was modest . nonetheless , a low recurrence and infection rate was confirmed as noted in other laparoscopic herniorrhaphy studies , and no mesh - related complications have been noted to date .\nonly 1 case of bowel adhesions to the edge of the mesh was found using ultrasound scanning at 24-month follow - up .\nsixty - five percent of our patients did not have adhesions of bowel or omentum detectable on ultra - sound examination .\nthis result is similar to that reported by franklin et al where two thirds of the patients had few or no adhesions .\na decreased inflammatory response in the abdominal wall tissue might limit the inflammatory tissue reaction caused by the pp mesh in regards to adhesion with underlying viscera .\nthe results of this study are important but somewhat limited by the fact that the results of individual sonographic examinations could not be independently verified .\nthe negative predictive value of the visceral slide method is approximately 80% ; therefore , it is possible that some patients who were deemed free of adhesions might indeed have had mild or filmy adhesions not detectable by ultrasound . in any case , these adhesions , even if present are unlikely to have any clinical impact , because no visceral complications have been observed .\nlate postoperative pain seemed to be mostly related to the suture points during strenuous activity .\nalthough it was noted by half of the patients , it usually did not require medication and did not interfere with work or recreational activities .\nwe have now gone to the use of absorbable monofilament material for the transfascial sutures .\nour early results indicate that laparoscopic ventral incisional hernia repair with pp mesh and omental coverage is not associated with sonographically detectable visceral adhesions in most patients . moreover , visceral complications such as bowel obstruction or enterocutaneous fistula do not occur .\nfurther accrual of patients and careful follow - up is needed to better understand the problem of ventral hernias and their repair with mesh .", "answer": "objective : laparoscopic repair of ventral incisional hernias is feasible and safe . \n polypropylene mesh is often preferred because of its ease of handling and lower cost . \n complications like adhesion and fistula formation can occur . \n the goal of this study was to determine whether bowel adhesions and their attendant complications could be prevented by interposition of omentum.methods:thirty patients underwent laparoscopic ventral incisional hernias repair with polypropylene mesh . \n omentum was always positioned over the loops of bowel for protection . at a mean follow - up of 14 months \n , 20 patients underwent ultrasonic examination using the previously described visceral slide technique to detect adhesions.results:the mean size of the hernias in the study was 50.3 cm2 , and the mean size of the mesh applied was 275 cm2 . \n thirteen patents ( 65% ) had no sonographically detectable adhesions . \n five patients demonstrated adhesions between the mesh and omentum , 1 patient developed adhesions between the left lobe of the liver and the mesh , and only 1 case of bowel adhesion to the edge of the mesh was found.conclusion:laparoscopic ventral incisional hernias repair with polypropylene mesh and omental interposition is not associated with visceral adhesions in the majority of patients . \n polypropylene mesh can be used safely when adequate omental coverage is available .", "id": 775} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 60-year - old male patient was referred to an otorhinolaryngology clinic due to a lump on the left side of his jaw , which had grown in 2 months .\nultrasound sonography test examination revealed a cystic mass that was 2417 mm in size with smooth contours .\nmultiple echogenic and reactive lymph nodes with partially visible hila were visualized in the neighboring upper jugular chain , with the largest being 1610 mm in size . following a neck magnetic resonance imaging and a preliminary diagnosis of wt ,\nleft superficial parotidectomy materials were sent for pathologic examination in two pieces , which were 53.22 cm and 4.531.2 cm in size .\ncross section analysis showed an off white - yellowish , well - contoured nodular tumor with a bleeding center of 42.52.2 cm .\nmicroscopic examination indicated that the tumor had epithelial components with basaloid and oncocytic columns of cells neighboring lymphoid components ( fig .\nin addition to the lymphoid follicles with distinct germinal centers , infiltration of large neoplastic cells with bizarre and extremely atypical morphology was seen in the lymphoid component ( figs . 2 , 3 ) .\n4b ) , leukocyte common antigen , igg , cd138 , mum1 , and focal positivity for kappa .\nstaining for lambda , igm , iga , cd3 , cd5 , cd10 , cd15 , cd56 , epithelial membrane antigen , bcl2 , bcl6 , cyclind1 , s100 , pancytokeratin , cytokeratin 20 , human melanoma black 45 , actin , and desmin were negative .\nlatent epstein - barr virus ( ebv ) was shown to be negative in tumor cells by using ebv - encoded rna chromogenic in situ hybridization . due to these findings\n, the patient was diagnosed with \" wt and cd30 positive diffuse large b - cell lymphoma in the parotid gland . \" following the lymphoma diagnosis , a full body screen was performed .\nin addition to these findings , the left suprarenal gland showed two nodular mass lesions , which were assessed as likely adenomas ; however , this preliminary diagnosis was not confirmed by histopathology .\nthe patient was stage 3a and received six courses of rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone ( r - chop ) therapy . during 6-month follow - up , the patient was free of disease .\nwt is the second most common type of salivary gland tumor . in 10 - 15% of cases , it is bilateral , and it accounts for 70% of all bilateral salivary gland tumors.2 the male / female ratio is 1.6/1 , and it typically develops in the 6th and 7th decades . smoking increases the risk of developing wt.5 microscopically the tumors are typically composed of proliferative epithelial components accompanied by lymphoid stroma with lymphoid follicles that have distinct germinal centers .\nhistogenesis of the lymphoid stroma in wt has been a topic of discussion for many years .\nlymphoid stroma can arise as a cell response to epithelial neoplasms or as a normal lymph node due to residue held by the epithelial neoplasm.5,6 the most widely accepted hypothesis suggests that wt is a neoplasm that develops in the heterotopic salivary gland ductus within or around the parotid lymph nodes.7 transformation to carcinoma in wt is a well - known phenomenon ; however , the development of lymphomas from wts is very rare.4,8 although some cases contain a normal residual lymphoid component , in others cases the lymphoid component contains entirely neoplastic lymphoid cells.4 in the present case , non - neoplastic lymphoid tissue was also present in the neighboring areas .\nthe pathogenesis of malignant transformation of wt remains unclear ; however , exposure to radiation is of particular interest , as the relationship between previous radiotherapy and lymphomas arising from wts has been determined by some authors.4,5,9 chronic immune sialadenitis is thought to play an important role , independent of the presence of sjgren syndrome symptoms.4,7,10 in this case , there was no history of radiotherapy or sialadenitis , but a history of smoking may have provoked the development of wt .\nsaxena et al.1 state that because the lymphoid stroma of wt is part of the systemic lymphoid tissue , in patients with lymphomatous spread of wt , disseminated disease is present during the staging either at the time of the diagnosis or after . in the present case ,\nwith screening techniques , lymphadenopathies of a pathologic size were found in the inguinal and iliac regions .\nsome researchers suggested that although the relationship between wt and lymphoma could be coincidental , it might also be of a pathogenic nature . according to the latter statement , a single agent can affect different tissues or one tumor could trigger the formation of another . from this point of view , the epithelial component is a continuous antigenic stimulator for the lymphoid component , which provides the stimulus for the development of lymphoma.1,6,8 according to this theory , the frequently observed reactive follicular hyperplasia in wt may be histological evidence of chronic antigen stimulation.1 it has been suggested that the lymphomas seen with wt are typically non - hodgkin lymphomas ; however , there are a few cases reporting hodgkin 's lymphomas.11,12 the majority of non - hodgkin 's lymphomas in wt are follicular lymphomas .\ndlbcl , small lymphocytic lymphoma , extranodal marginal zone lymphoma of mucosa associated lymphoid tissue , and mantle cell lymphoma have also been reported.4,6,8,9 a small number of t - cell lymphomas such as peripheric t - cell lymphoma and t - cell lymphoblastic lymphoma have also been described in wt.4,8,13 in summary , malignant lymphomas in wt are very rare .\nthe presented case is a diffuse large b - cell lymphoma expressing cd30 positivity . to the best of our knowledge\nthis is the first case in literature describing dlbcl with expression of cd30 in wt .", "answer": "warthin 's tumor is the second most common type of salivary gland tumor . \n microscopically , warthin 's tumor displays a proliferative epithelial component and lymphoid stroma . \n carcinomas arising from the epithelial component are well known , but malignant transformations of the lymphoid stroma are rare . when they do occur , they are most commonly b - cell type non - hodgkin lymphomas . a 60-year - old male patient \n underwent surgical resection of a parotid mass . \n after superficial parotidectomy , microscopic examination indicated that the tumor was of epithelial components with basaloid and oncocytic columns of cells neighboring lymphoid components . \n in addition to the lymphoid follicles with distinct germinal centers , there were large , bizarre and extremely atypical neoplastic cells seen in the lymphoid component . \n large neoplastic cells were diffusely cd20 and cd30 positive . the patient was diagnosed with \" warthin 's tumor and diffuse large b - cell lymphoma with expression of cd30 . \" \n the histopathologic and clinical features are discussed along with a review of the literature .", "id": 776} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrab - type small gtpases are conserved membrane trafficking proteins in all eukaryotes , and they mediate various steps in membrane trafficking , including vesicle budding , vesicle movement along cytoskeletons , vesicle docking to specific membranes , and vesicle fusion .\nrabs function as a molecular switch by cycling between two nucleotide - bound states , a gdp - bound inactive state ( off state ) and a gtp - bound active state ( on state ) .\nrabs are activated by specific guanine nucleotide exchange factors ( gefs ) , which promote the release of gdp from rab and binding of gtp to rab , and the activated rabs are then inactivated by gtpase - activating proteins ( gaps ) or spontaneously inactivated by their intrinsic gtpase activity .\nthus , investigation of rab - gefs is crucial to understanding the spatio - temporal regulation of rab gtpase activation .\nalthough a large number of putative rab - gefs , including denn - domain - containing proteins , have recently been reported , very little is known about their in vivo roles in rab targeting to specific membrane compartments .\nrab17 was originally described as an epithelial cell - specific rab isoform that regulates polarized trafficking but was subsequently found to be expressed in melanocytes and human breast adenocarcinoma , and more recently we demonstrated that rab17 is also expressed in mouse brain .\nlocalization of rab17 in mouse hippocampal neurons is unique , because rab17 is the only rab isoform that is specifically targeted to the dendrites and is not targeted to the axon .\nthe targeting of rab17 to the dendrites is neuronal differentiation stage - dependent : at an early stage ( 3 d of in vitro culture ) it localizes only in the cell body , whereas at a later stage ( 11 d of in vitro culture ) some of the rab17 is translocated from the cell body to the dendrites .\nby contrast , other rab isoforms are targeted to the axon alone ( e.g. , rab3a ) or to both the axon and dendrites ( e.g. , rab5a ) .\ntargeting of rab17 to the dendrites is known to be crucial for dendrite morphogenesis and subsequent postsynapse formation , because knockdown of rab17 has been found to result in a marked reduction in both total dendrite length and the number of dendrite branches without affecting axon morphogenesis ( i.e. , total axon length and the number of axon branches ) .\nalthough several mammalian rab isoforms ( e.g. , rab7 and rab11 ) have been shown to regulate dendrite morphogenesis , rab17 is the first reported rab isoform that specifically regulates dendrite morphogenesis , but not axon morphogenesis , in mammalian neurons .\nwe therefore thought that rab17 would be an ideal rab isoform to use to analyze a rab targeting mechanism at the cellular level .\nhowever , until recently the molecular basis of the specific rab17 targeting to dendrites had completely remained unknown and no physiological rab17-gefs that function in hippocampal neurons had been identified . in our latest study , we screened for rab17-gefs by performing yeast two - hybrid assays with a constitutive negative mutant of rab17 as bait and succeeded in identifying rabex-5 and als2 , both of which were originally described as rab5-gefs , as plausible candidate rab17-gefs in mouse hippocampal neurons .\nit is noteworthy that overexpression of rabex-5 , but not of als2 , increased the proportion of rab17 in the dendrites , whereas knockdown of rabex-5 caused a dramatic reduction in the proportion of rab17 in the dendrites .\nimportantly , overexpression of a gef - activity - deficient mutant of rabex-5 ( rabex-5-d313a ) failed to increase translocation of rab17 from the cell body to the dendrites .\nbased on these findings , activation of rab17 by rabex-5 is responsible for the stage - dependent movement of rab17 from the cell body to the dendrites of hippocampal neurons . actually , forced activation of rab17 , i.e. , expression of a constitutive active mutant of rab17 ( rab17-q77l ) , increased the dendrite localization of rab17 even in early stage neurons .\nmore importantly , rabex-5 knockdown was found to cause a significant reduction in total dendrite length , the same as rab17 knockdown did , and the reduction was partially rescued by co - expression with rab17-q77l .\nthese findings indicated that rabex-5 functions as an upstream activator of rab17 in developing hippocampal neurons ( fig . \nproposed model of rabex-5-mediated translocation of its downstream rabs to the neurites of developing hippocampal neurons .\nrabex-5 functions not only as a rab17-gef ( a ) but also as a rab5/21-gef ( b ) , and it determines dendrite targeting of rab17 and axon / dendrite targeting of rab5/21 , respectively ( dotted arrows ) .\nthe solid arrows indicate the gef function of rabex-5 that promotes release of bound gdp from rab5/17/21 in exchange for gtp . because of the different sorting functions of rabex-5\n, rab17 specifically regulates dendrite morphogenesis , whereas rabex-5 and rab5 are involved in neurite morphogenesis in general . factor \nx in ( a ) is a putative rab17-specific effector that may also interact with rabex-5 and support dendrite targeting of rab17 .\nrabaptin-5 is known to interact with both rab5/21 and rabex-5 at early endosomes , but whether rabaptin-5 is involved in neurite outgrowth remains to be determined ( b ) .\ndetermining the molecular mechanism by which active rab17 is translocated from the cell body to the dendrites is an important task that has yet to be achieved .\nactive rab17 itself is unlikely to have the ability to target dendrites , because unlike endogenous rab17 , which specifically localizes in the dendrites , rab17-q77l also localizes in the axon .\ninterestingly , overexpression of a gef domain ( i.e. , vps9 domain ) of rabex-5 alone similarly increased the translocation of rab17 to both the axon and the dendrites , whereas overexpression of full - length rabex-5 increased endogenous rab17 translocation to the dendrites alone .\nthus , some additional domains of rabex-5 besides its gef domain ( e.g. , a zinc finger domain and/or a coiled - coil domain ) must also be involved in rab17 targeting .\nwe speculate that rabex-5 functionally links to dendrite - directed motors and that rab17 activated by rabex-5 is captured by certain motor proteins that transport it to the dendrites .\nsince some rab effector molecules ( or rabs themselves ) are known to directly associate with motor proteins , in the future it would be interesting to search for rab17-specific effectors that form a link between rabex-5 and motor proteins .\nour finding that rabex-5 determines the dendrite localization of its downstream target rab17 is highly consistent with a recent report showing that rab - gefs ( e.g. , rabex-5 and rabin8 ) are major determinants of specific rab membrane targeting .\nhowever , one puzzling result of our research is that rab5 and rab21 , two other downstream targets of rabex-5 , are translocated both to the axon and to the dendrites of developing hippocampal neurons in a rabex-5-dependent manner ( fig . \n1b ) , meaning that rabex-5 determines not only the dendrite targeting of rab17 but the axon / dendrite targeting of rab5 and rab21 as well .\nbecause of the multiple roles of rabex-5 in rab targeting to neurites , rabex-5 is involved in both the axon morphogenesis and dendrite morphogenesis of developing hippocampal neurons by activating at least two downstream targets , rab5 and rab17 .\nhowever , the molecular mechanism by which rabex-5 sorts different downstream rab proteins into the axon and/or dendrites is completely unknown .\nsince rabex-5 constitutes a gef cascade by recruiting a rab5 effector , rabaptin-5 , to early endosomes , rabex-5 may also recruit an as yet unidentified rab17-specific effector(s ) ( factor x in fig . \n1a ) that does not bind rab5 or rab21 and support dendrite targeting of rab17 . thus , identifying rab17-specific effectors will be one of the most important tasks in future rab17 research designed to understand the molecular mechanism by which rabex-5 determines the targeting of its downstream rab proteins to neurites at the cellular level . since rab17 is also expressed in epithelial cells and melanocytes , it would be interesting to investigate whether rabex-5 also contributes to the polarized trafficking of rab17 in other cell types .", "answer": "rab family small gtpases function as molecular switches in the regulation of membrane traffic , and their activity is thought to be controlled by guanine nucleotide exchange factors ( gefs ) . \n however , the role of gefs in targeting rab proteins to specific membrane compartments is poorly understood . \n we have recently reported finding that rabex-5 , originally described as a rab5-gef , also functions as a rab17-gef in mouse hippocampal neurons . \n the rab17 in developing hippocampal neurons is specifically targeted to their dendrites and not to their axons , and the gef activity of rabex-5 is required for translocation of rab17 from the cell body to the dendrites . \n interestingly , rabex-5 is also required for the axon and dendrite localization of rab5 and rab21 in hippocampal neurons . \n our findings indicate that rabex-5 determines the targeting of its downstream rab proteins to the dendrites ( rab17 ) or to both the axon and dendrites ( rab5 and rab21 ) .", "id": 777} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmedical files of the patients who were referred to the outpatient clinics of children s health and diseases of namik kemal university research , and application hospital were analyzed , and height , bodyweight , waist , and hip circumferences of the patients were recorded . among these cases ,\npatients who had undergone complete word counts because of medical requirement or routine control were included in the study , and their neutrophil , and lymphocyte parameters were evaluated . medical files or the patients were screened , and those with viral - bacterial infection , insulin - dependent diabetes , congenital metabolic disease or hormonal disorder were excluded from the study group . a total of 130 obese ( aged 615 years ) and 57 ( aged 715 years ) healthy control subjects were included in the study .\nage , and measured body parametres of the healthy control , and obese individuals participating in the study body mass indices ( bmis ) of the children were estimated based on bmi percentiles established by the centers for disease control 2000 ( cdc ) for children , and adolescents .\nparticipants with bmis between 8595 percentiles were defined as overweight , and those over 95 percentile as obese .\nblood samples to be analyzed for neutrophils , lymphocytes , and other hemogram parametres were placed in tubes containing k2 edta . following 15 minutes of agitation , the samples were analyzed in pentra dx nexus ( uk ) device under room temperature . for biochemical measurements\nall biochemical tests were performed in cobas c 501 roche ( japan ) biochemical analyzer using commercial kits . in all analyses spss 17.0 ( chicago , il . )\nnormality of continuous variables was checked with kruskal - wallis test . for comparison of data with non - normal distribution mann- whitney\nmedical files of the patients who were referred to the outpatient clinics of children s health and diseases of namik kemal university research , and application hospital were analyzed , and height , bodyweight , waist , and hip circumferences of the patients were recorded . among these cases ,\npatients who had undergone complete word counts because of medical requirement or routine control were included in the study , and their neutrophil , and lymphocyte parameters were evaluated . medical files or the patients were screened , and those with viral - bacterial infection , insulin - dependent diabetes , congenital metabolic disease or hormonal disorder were excluded from the study group . a total of 130 obese ( aged 615 years ) and 57 ( aged 715 years ) healthy control subjects were included in the study .\nage , and measured body parametres of the healthy control , and obese individuals participating in the study body mass indices ( bmis ) of the children were estimated based on bmi percentiles established by the centers for disease control 2000 ( cdc ) for children , and adolescents .\nparticipants with bmis between 8595 percentiles were defined as overweight , and those over 95 percentile as obese .\nblood samples to be analyzed for neutrophils , lymphocytes , and other hemogram parametres were placed in tubes containing k2 edta . following 15 minutes of agitation , the samples were analyzed in pentra dx nexus ( uk ) device under room temperature . for biochemical measurements\nall biochemical tests were performed in cobas c 501 roche ( japan ) biochemical analyzer using commercial kits .\nnormality of continuous variables was checked with kruskal - wallis test . for comparison of data with non - normal distribution mann- whitney\nmeasured parametres of a total of 187 healthy , and obese children are given as median , minimum , and maximum values in table 2 .\nobese , and healthy control groups were compared , and lymphocyte , and neutrophil ratios were found to be significantly higher in the obese group ( p=0.03 , and 0.045 , respectively ) .\nsimilarly , neutrophil / lymphocyte ratio , and crp levels were found to be significantly higher in the obese group ( p=0.03 , p=0.02 , and p=0.00 ) .\nbesides , mean platelet volume ( mpv ) was significantly higher in the obese group ( p=0.005 ) . both groups did not differ significantly as for platelet / lymphocyte ratio ( p=0.156 ) biochemical , and hematological parametres measured in healthy controls , and obese individuals p<0.05 statistically significant ; hgb : hemoglobin ; hct : hematocrit ; mcv : mean corpuscular volume ; mch : mean corpuscular hemoglobin ; mchc : mean corpuscular hemoglobin concentration ; rdw : red blood cell distribution width ; wbc : white blood cell ; mpv : mean platelet volume ; pdw : platelet distribution width ; crp : c - reactive protein .\nin recent years because of diets rich in fats , and sedentary life style , prevalence of obesity has rapidly increased .\nobesity plays a central role in insulin resistance which include hyperinsulinemia , hypertension , hyperlipidemia , and type-2 diabetes , and increases the risk of cardiovascular disease .\nalthough , obesity has been demonstrated to be an independent risk factor for atherosclerotic cardiovascular diseases , the mechanism of increased cardiovascular risk in obese individuals has not been clarified yet . in studies performed , the pathogenesis of pathological processes of atherosclerotic cardiovascular disease , and related risk factors have been dated back to the pediatric age .\nobesity is a chronic inflamatory disease characterized by altered adipokine production , and increase in the levels of inflammatory cytokines .\nkim et al . analyzed levels of leptin , and inflammatory cytokines including hs - crp , tumor - necrosis factor ( tnt- ) , interleukin-6 ( il-6 ) in young obese girls , and they were found to be significantly higher in obese women relative to non - obese women . in recent studies increased levels of crp were detected in obese individuals [ 14 , 15 ] .\nhigh - sensitive c - reactive protein ( hs - crp ) which can be used as a marker of metabolic syndrome is a useful marker of childhood obesity .\nprevention of obesity , and inflammation which start in childhood will contribute to the prevention of metabolic syndrome in the future .\nsimilarly , crp level in the obese group was found to be significantly higher in our study when compared with the healthy controls .\narslan and makay have demonstrated that mpv levels were higher in obese adolescents with non - alcoholic fatty liver when compared with healthy controls , and other obese patient groups . however , kilciler et al .\nreported that any significant difference was not found between the patients with non - alcoholic fatty liver disease as for mpv levels .\nalso in our study , we detected higher mpv levels in the obese patient group when compared with the healthy controls .\nnlr which is a strong indicator of inflammation has been investigated in various inflammatory , and neoplasic diseases including metabolic syndrome , behcet s disease , coronary artery disease [ 21 , 22 ] , heart failure [ 23 , 24 ] , colorectal cancer , chest , and lung diseases , and hepatocellular carcinoma .\nthe main fundamental etiological factor of this wide spectrum is that nlr contains two separate inflammation markers .\nneutrophils have been reported to migrate into ischemic myocardial tissue before other inflammatory cells , and cause destructive changes by stimulating release of proteolytic enzymes , reactive oxygen radicals , and neutrophils . as a known fact ,\nin the pathophysiology of atherosclerotic cardiovascular diseases , increased inflammation , and endothelial dysfunction play fundamental roles .\noutcomes of this study suggest that nlr may be one of the markers of endothelial dysfunction , and inflammation in obese patients .\nrelated studies performed in adults have suggested that various comorbidities as diabetes , insulin resistance , hyperlipidemia , and coronary artery disease prevent disclosure of cause - effect relationship between obesity , and inflammation .\ntherefore this study provides a clarification on this issue which also aids in the evaluation of this correlation between obesity , and inflammation . in conclusion , in chidhood obesity ,\ntherefore keeping obesity under control using dietary modifications , and other treatment methods carries importance in decreasing mortality , and morbidity rates in adulthood .", "answer": "objective : obesity is a growing health problem in most of the developed countries . it is associated with many chronic diseases , affecting particularly endocrine and cardiovascular systems . inflammation plays a key role in pathophysiology of obesity . in this study , we aimed to investigate the inflammation status in obese children using neutrophil / lymphocyte ratio.methods:in this study 130 obese and 57 healthy children were assessed retrospectively . according to centers for disease control 2000 ( cdc ) bmi percentiles for childhood and adulthood , \n 8595 percentile was considered as overweight and > 95 percentile as obese.results:lymphocyte/neutrophil ratios in the obese group were significantly higher compared to those in healthy controls ( p=0.03 and p=0.045 , respectively ) \n . neutrophil / lymphocyte ratio and crp level in the obese group were significantly higher compared to those in healthy controls ( p=0.02 and p=0.00 , respectively ) . \n thrombocyte / lymphocyte ratios were not significantly different between two groups ( p=0.156).conclusion : it is possible that childhood obesity which has been increasingly prevalent recently triggers the pathogenesis of atherosclerosis during the early years of life . increased neutrophil / lymphocyte ratio might be associated with the severity of inflammation which plays a role in the early stages of atherosclerosis . therefore , \n taking childhood obesity under control using diet and other treatment methods will prevent mortality and morbidity in the elderly .", "id": 778} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nheterozygous hnf4a mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes .\nautosomal dominant idiopathic fanconi syndrome ( a renal proximal tubulopathy ) is described but no genetic cause has been defined .\nwe report six patients heterozygous for the p.r76w hnf4a mutation who have fanconi syndrome and nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia . all six displayed a novel phenotype of proximal tubulopathy , characterised by generalised aminoaciduria , low molecular weight proteinuria , glycosuria , hyperphosphaturia and hypouricaemia , and additional features not seen in fanconi syndrome : nephrocalcinosis , renal impairment , hypercalciuria with relative hypocalcaemia , and hypermagnesaemia .\nthis was mutation specific , with the renal phenotype not being seen in patients with other hnf4a mutations .\nin silico modelling shows the r76 residue is directly involved in dna binding and the r76w mutation reduces dna binding affinity .\nthe target(s ) selectively affected by altered dna binding of r76w that results in fanconi syndrome is not known .\nthe hnf4a r76w mutation is an unusual example of a mutation specific phenotype , with autosomal dominant atypical fanconi syndrome in addition to the established beta cell phenotype .", "answer": "backgroundmutation specific effects in monogenic disorders are rare . \n we describe atypical fanconi syndrome caused by a specific heterozygous mutation in hnf4a . \n heterozygous hnf4a mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes . \n autosomal dominant idiopathic fanconi syndrome ( a renal proximal tubulopathy ) is described but no genetic cause has been defined.methods and resultswe report six patients heterozygous for the p.r76w hnf4a mutation who have fanconi syndrome and nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia . \n all six displayed a novel phenotype of proximal tubulopathy , characterised by generalised aminoaciduria , low molecular weight proteinuria , glycosuria , hyperphosphaturia and hypouricaemia , and additional features not seen in fanconi syndrome : nephrocalcinosis , renal impairment , hypercalciuria with relative hypocalcaemia , and hypermagnesaemia . \n this was mutation specific , with the renal phenotype not being seen in patients with other hnf4a mutations . \n in silico modelling shows the r76 residue is directly involved in dna binding and the r76w mutation reduces dna binding affinity . \n the target(s ) selectively affected by altered dna binding of r76w that results in fanconi syndrome is not known.conclusionsthe \n hnf4a r76w mutation is an unusual example of a mutation specific phenotype , with autosomal dominant atypical fanconi syndrome in addition to the established beta cell phenotype .", "id": 779} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary tumors of the trachea are rare and account for 0.1% of all malignancies . in adults ,\napproximately 90% of the primary tracheal tumors are malignant , whereas in children , the majority of these tumors are benign [ 2 , 3 ] . in a retrospective study by webb et al . , 55.4% of the patients were male and 77.3% of them were smokers .\nthe frequency of this rare disease has been estimated to be 0.10.4% of all malignancies , with an annual incidence of 2.6 new cases per million per year .\nprimary tracheal tumors can arise from the respiratory epithelium , salivary glands and mesenchymal structure of the trachea .\nsquamous cell carcinoma ( scc ) and adenoid cystic carcinoma ( acc ) make up about 71.6% of all adult primary tracheal tumors . the remaining portion ( 28.4% )\nscc occurs predominantly in men in the sixth and seventh decades , whereas acc is equally distributed between the sexes and peaks in incidence in the fourth and fifth decades .\nin contrast to acc , scc ( the most common type of tracheal tumors ) has a more aggressive course .\nmedian survival time ranges from 6 to 14 months , and tumor disappearance is dependent on whether the primary lesion is resected .\nsccs spread to the lymph nodes and 1020% of the patients will have distant metastasis at presentation .\ncarcinoids , lymphomas , granular cell tumors and small cell carcinomas have variable prognoses ; yet they seem to behave better than sccs , adenocarcinomas or sarcomas .\nthe majority of the tracheal neoplasms are primary in nature , and other primary sites that can metastasize to the trachea are the lung and esophagus , the latter being the most common .\npatients with surgically resectable primary tracheal tumors have a better prognosis than those with tumors that can not be resected .\npreoperative radiation therapy has been attempted in some patients , yet the most compelling evidence for adjuvant radiation therapy comes from postoperative cases .\nthe present study reports a rare case of primary tracheal malignancy treated with surgery and adjuvant radiation therapy .\nour 60-year - old diabetic and hypertensive male patient had a 1-month history of cough associated with marked respiratory distress and occasional dyspnea in the right lateral lying position .\nthe patient consulted a chest physician and underwent bronchoscopy , which showed a polypoid growth in the trachea extending to the larynx ( fig .\na computed tomography ( ct ) scan revealed irregular soft tissue thickening in the region of the trachea extending up to the adjacent larynx with no soft tissue calcification , and there was no definite lymphadenopathy in the cervical region and no involvement of the underlying bone . a repeat ct scan of the neck ( fig .\n2 ) showed evidence of an ill - defined , irregular , nodular , infiltrating soft tissue growth arising from the posterior tracheal wall , bridging the lumen and reaching up to the anterior wall , with an infiltration of about 2.2 1.8 cm .\nthe location was opposite the c7-d1 level involving the 5th or 6th tracheal ring , approximately 7 cm proximal to the carina with no significant evidence of cervical and mediastinal lymphadenopathy .\nexcision of the tracheal growth through a cervical transverse incision was performed , and a tracheostomy tube was inserted .\nsoon after surgery , the cough subsided and the patient attended square hospital , dhaka , bangladesh , for postoperative irradiation .\nninety - five percent of the planning target volume ( ptv ) covered 97.3% of the prescribed dose .\nthe minimum and maximum dose received by the ptv was 50.05 and 63.68 gy , respectively .\n3 ) . three multileaf collimator fields ( left anterior oblique , right anterior oblique and posterior ) were used for three - dimensional conformal radiation therapy ( 3dcrt ) .\ncomplete response was documented , and the patient is still alive without any evidence of disease during 30 months of follow - up .\nprimary malignant tumors of the trachea are uncommon , and therefore limited data supporting a standard management are available .\nthe vast majority of the primary tracheal tumors in adults are malignant and most of them usually diagnosed at a later stage , which is due to a delayed presentation of specific symptoms like cough , dyspnea and hemoptysis .\nit is clear that patients who can be resected have a better prognosis than those who can not , prompting the recommendation of surgical resection for most primary tracheal tumors .\nall resected patients need postsurgical irradiation , regardless of tumor burden , margin status , histology or nodal status .\ngrillo and mathisen experienced a median survival of 34 months in scc and 118 months in acc patients who underwent a combined modality like surgery and radiation therapy .\nattained a 61-month median survival using a combined surgery and radiation therapy in their study .\n. showed that 73% of the patients with a 5-year survival underwent radiation therapy postoperatively .\nthe role of external beam radiation therapy as an adjuvant to surgical resection is better established .\ngrillo and mathisen advocated maximal ( 4,5006,500 cgy ) radiation therapy after scc and acc resection because of the close margins necessary for resection and the high likelihood of local recurrence .\nmodern ct - based 3dcrt or intensity - modulated radiation therapy theoretically allows higher and safer doses delivered to the trachea . for postoperative cases ,\nall patients with this tumor in the postoperative or definitive setting should be treated with the 3dcrt technique .\nan intraluminal boost technique after external beam radiation therapy may decrease the risk of late side effects .\nthere are many studies showing the benefit of postoperative irradiation therapy in primary tracheal malignancies such as sccs and accs .\nhowever , little experience has been shared in the case of primary adenocarcinomas of the trachea , the tumor type described in our report .\nthe prognosis of patients with malignant tumors of the trachea remains gloomy , and long - term median survival of tracheal adenocarcinoma patients undergoing combined modalities is unknown to us .\nprimary adenocarcinoma of the trachea needs to be diagnosed at an early stage , and combined multimodal approaches may be explored to attain an extended median survival .\nnone of the authors has any conflicts of interest regarding the content of this article .", "answer": "primary adenocarcinoma of the trachea is extremely rare and a standard treatment does not exist due to nonavailability of evidence - based randomized control studies . this paper reports the case of a 60-year - old male , who presented with cough and occasional respiratory distress . \n bronchoscopic examination and a computed tomography scan revealed a soft tissue mass in the trachea arising from the posterior tracheal wall . \n cytological examination and immunochemistry confirmed primary adenocarcinoma of the trachea . \n excision of the tumor followed by three - dimensional conformal radiation therapy was performed , and a dose of 56 gy was delivered to the primary site . \n two and a half years after treatment , the patient has no clinical or radiological evidence of the disease , and no late complication has occurred .", "id": 780} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhyperparathyroidism ( hpt ) occurs when there is an abnormal increase in parathyroid hormone ( pth ) production by the parathyroid gland [ 13 ] .\nprimary hpt ( phpt ) is caused by parathyroid adenomas in 85% of cases , leading to hyperplasia and over - secretion of pth . in most individuals in western society , it is diagnosed at an asymptomatic stage , without signs or symptoms of ( pth ) calcium excess .\ninitial symptoms are nonspecific , such as weakness , malaise , fatigue and possible mood disturbances . if not diagnosed and left untreated , it leads to devastating consequences including nephrolithiasis , nephrocalcinosis , renal failure , osteopenia and osteoporosis .\na 22-year - old male student presented to our hospital with a 2-year history of progressive lower extremity weakness .\none year prior to the admission , he had been seen at another medical clinic because of fatigue and difficulty walking .\nhis radiographs showed no fractures , and he was referred to physiotherapy for muscle strengthening .\nfurther questioning revealed that , despite physiotherapy , his weakness had progressed and he had to quit school as he was having considerable difficulty walking up a flight of stairs .\na thorough investigation was performed and showed a serum calcium level of 3.46 mmol / l ( normal : 2.12.6 mmol / l ) and a pth level of 138 pmol / l ( normal : 1.69.3 pmol / l ) .\nhe was referred to our general surgery service where he was admitted for excision of the parathyroid adenoma . upon admission ,\none day prior to the scheduled parathyroidectomy , he had a simple , low - energy fall while he was walking on his own to the hospital .\nradiographs revealed a displaced subcapital fracture of his left hip , a segmental fracture of his right humerus and extreme osteopenia ( fig . 1 ) . \n\nfigure 1:(a ) left femoral neck displaced subcapital fracture and ( b ) right humeral shaft segmental fracture .\n( a ) left femoral neck displaced subcapital fracture and ( b ) right humeral shaft segmental fracture .\none day after sustaining this injury , the patient underwent an uncemented left total hip arthroplasty ( tha ) ( fig . \n2 ) , and acetabular fixation was supplemented with multiple screws , and he maintained touch - down weight bearing for 6 weeks postoperatively .\npostoperatively , the pth level had decreased to 4.9 pmol / l , and the calcium level had returned to normal at 2.42 mmol / l .\nthe calcium level continued to fall , and 2 weeks after the parathyroidectomy , it had reached 1.70 mmol / l . after a further 20 days , it started to normalize and then continued to remain stable , as shown in fig . 3 . \n\nfigure 2:(a ) left thr and ( b ) right humerus in a brace . \n\n( a ) left thr and ( b ) right humerus in a brace . a graph for calcium level from admission to 7 weeks after surgery\nwe report this case to illustrate the importance of early detection and diagnosis of phpt , which was possible in this young and presumed healthy individual if proper assessment and management were done .\nfurthermore , sending him for physiotherapy without a clear diagnosis increased the likelihood of missing the diagnosis and progression of the disease .\nsolitary parathyroid adenoma is the most common cause of phpt , representing 8590% of cases .\nsymptomatic phpt with skeletal , renal , abdominal and neuro - psychiatric manifestations has become exceedingly rare in developed countries .\nour patient was unusual in that he was not diagnosed early and presented with skeletal manifestations resulting in multiple fractures including femoral neck fracture ( fnf ) , which was treated with total hip replacement ( thr ) . at this young age , thr would affect his lifestyle and put him at risk of revision surgery early in his life .\nthe literature clearly shows that the earlier hpt is detected , the more reversible the disease .\nwe believe that , despite the young age of our patient , thr was still the preferred treatment in this situation owing to his poor bone quality , which could have led to failure of fixation ; in addition , severe fracture displacement carries a high risk of femoral head avascular necrosis .\nyang et al . found that salvage tha for failed internal fixation following fnf is a more technically demanding procedure with prolonged operative time and larger amounts of postoperative drainage ( within 24 h ) and that patients are at increased risk of developing hip complications compared with primary thr for acute displaced fnf .\nfrench et al . reported a case of a 21-year - old male with parathyroid adenoma who had presented with a left femoral shaft fracture and right fnfs .\nalthough these were treated with fixations , the right side required conversion to thr within a year of his presentation .", "answer": "we present the case of a 22-year - old male with longstanding progressive fatigue , weakness and pain around his hips due to an undiagnosed parathyroid adenoma . \n the resultant primary hyperparathyroidism ultimately caused pathologic fractures . \n he was admitted to the hospital for further assessment and excision of the parathyroid adenoma . \n a few days after admission , he fell down while walking and was referred to our team . \n x - rays showed a displaced left femoral neck fracture ( fnf ) and right humeral shaft fracture with poor bone quality . \n his humeral fracture was treated conservatively , and the fnf was treated with total hip replacement . \n three days later , he underwent parathyroidectomy . \n this case demonstrates the importance of a thorough investigation of progressive weakness even in a young individual and illustrates the importance of early diagnosis of parathyroid adenoma to avoid the devastating end results of this condition .", "id": 781} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\none of the most major public health problems over the world is cardiovascular disease including coronary heart disease ( chd ) , peripheral vascular disease and stroke.1 countries in the middle east bear a heavy burden from chd .\nthe prevalence of chd is due to high rate of its risk factors , particularly obesity , smoking , hypertension ( htn ) , dyslipidemia , diabetes , and sedentary lifestyles .\npatients in the middle east present with myocardial infarction at a younger age , on average , compared with patients elsewhere .\nthe projected future burden of mortality from chd in the middle east is set to outstrip that observed in other geographical regions.2 improved socioeconomic conditions in saudi arabia during the past few decades have been accompanied by rapid changes in the lifestyle of the people , particularly unhealthy dietary patterns , and physical inactivity .\nconsequently , chronic diseases commonly associated with affluent societies , such as chd , diabetes mellitus ( dm ) , obesity have become the dominant illnesses in saudi arabia .\nhospital - based studies have shown that smoking , htn , and dm are common risk factors among patients with acute myocardial infarction .\na recent study on chd mortality in the eastern province of saudi arabia , using proportionate mortality ratio , showed that 26% of deaths were caused by chd ( 27.0% of male and 23.5% of female deaths).3 in 2013 , there was study on the prevalence of the obesity in saudi arabia which showed that 28.7% were obese ( body mass index [ bmi ] > 30 ) .\nobesity consider as an important risk factor of chd.4 one study in the east province of saudi arabia in 2008 showed that 21% was the prevalence of htn in screening campaign and increase with age , lower educational level , and divorced women.5 in 2009 , there was study on the prevalence of dm in saudi arabia .\nthe prevalence of dm was 30% and dm increase with obesity and female gender , who more than 50 years compare to male group.6 a national study measured hyperlipidemia and 5-year risk of development of chd among university and school workers in jeddah , saudi arabia .\nabout half of the participants were overweight , 18.8% were current cigarette smokers and 19.9% were hypertensive .\nhyperlipidemia was present in 10.1% and was significantly related to older age ( 40 years and over ) and place of work . according to the previous study , the estimated risk of chd in the coming half - decade for those classified in the fifth quintile was 0.068.7 the government of saudi arabia is becoming increasingly concerned about the high prevalence of chd risk factors .\nknowledge of the causative factors and methods of prevention of chd are essential to reduce morbidity and mortality from them .\nthe objective of this study is to determine the prevalence of chd risk factors among the faculty and staff members of qassim university and also to assess their knowledge of the risk factors of chd and compare the result with other prevalence of risk factors in other area of saudi arabia .\na cross - sectional study was conducted among the faculty and the staff members of qassim university for male and female .\nall employees were invited to voluntarily participate in the study by advertisement through email and social network .\ndata were collected through a self - administered health risk assessment questionnaire , as well as through clinical screening that included measurement of blood pressure , fasting blood glucose ( fbg ) and lipid profile .\nthe employees working under contract for an outsourcing company ( for example , the housekeeping staff ) were excluded .\nparticipants were recruited through general announcements to staff , as well as among patients visiting the clinic .\nthis sample is expected to provide sufficiently reliable estimates of the most common risk factors among university staff and faculty .\na self - administered questionnaire was used to collect information on sociodemographic , biological , and behavioral risk factors .\ninformation was collected on personal , past and family history of chronic diseases , cigarette smoking , and stress experienced in the workplace .\nwe also documented the level of willingness of the participants to engage in a behavior change program .\ndata were focused on providing point estimates for the risk factors of chd and testing hypotheses regarding expected correlations between these risk factors . the odd ratio and 95% confidence interval were calculated .\nwe present the results of analysis of data from 233 faculty / staff members ( 157 males , 67% ; 76 females , 33% ) .\nmore than half of the participants were in the 30 - 49 year age group .\n53.6% of study participants have family history of any of risk factor of chd and 20.6% of the staff members and faculties were obese 10.3% were diabetic .\nsociodemographic data and risk factor status the most common age group for male who are overweight is more than 50 and for obese is between 30 and 50 years . for female gender we can find the most common age group for overweight and obese is between 30 and 50 years ( 35.7% and 30.2% ) , respectively ( table 2 ) .\nprevalence of obesity among male and female there were 16 of the staff members newly diagnosed to have impaired fasting glucose ( 13 male , 3 female ) .\n20 of the staff members and faculties were found to have newly diagnosed dm . when the age increase in both gender , the chance of development of dm will be increase with no significant p value as shown in table 3 .\nregarding the blood pressure , we found the blood pressure was increased with age and there was no significant difference between male and female ( table 3 ) .\nprevalence of dm and htn according to the gender and age group in table 4 , we found that the smoking behavior is among male gender only and there was no smoking behavior among female gender .\nrelation of gender , age group , and smoking status youngest age group < 30 was expected to have increase in high - density lipoprotein ( hdl ) in both gender ( male and female ) .\nlow - density lipoprotein ( ldl ) more than 190 mg / dl in age group more than 30 years for both genders ( male and female ) as shown in table 5 .\nin our study , the prevalence of dm , dyslipidemia , and smoking was found to be lower than other studies.8,9 according to the 2011 american diabetic association guidelines , based on fbg , 6.9% of the participants were found prediabetic and 8.6% having diabetes .\nfbg values were found significantly higher with increasing age especially among more than 50 years old .\nno statistically significant difference was found among males or females in the prediabetic category ( p = 0.441 ) .\nthe ldl levels were found to increase with age with participants more than 50 years of age having ldl values > 190 mg / dl ( p = 0.001 ) .\na study carried out among saudi diabetic patients attending primary health - care ( phc ) service concludes that uncontrolled diabetes was found to be the common risk factor followed by uncontrolled lipid profile , obesity , uncontrolled systolic blood pressure , and smoking .\nthe result of study revealed that seven percent ( 7% ) of male group felled in highest risk group in comparison with 1% in female group ( p < 0.05 ) , while 31% in male group felled in mild risk group in comparison with 90% in female group ( p\n62% in male group felled in high - risk group in comparison with 9% in female group ( p < 0.05).10\nthe directorate of scientific research at king abdul aziz city for science and technology recognized that there is a major transition going on in the kingdom in terms of lifestyle , featuring a more sedentary lifestyle , increased consumption of fast food and unhealthy diet .\nthese changes were associated with rapid socioeconomic development , urbanization , and increased purchasing power of the population.2 various other studies in the kingdom have similarly indicated a rise in the lifestyle - related risk factors.11,12 moreover , dm and obesity are the leading risk factors associated with chd .\ntheir study done in king faisal specialist hospital in 2011 showed the prevalence of dm was 30%.6 while the prevalence of obesity is 64% and 70% among males and females , respectively.13 our study aimed to estimate the prevalence of risk factors of chd among qassim university s staff / employees .\nthe overall prevalence of these risk factors ( dm , dyslipidemia , obesity and overweight , smoking , and sedentary lifestyle ) which is found to be 30% in our study was similar to several other studies done elsewhere in similar setups in educational institutions,12 but was significantly lower than the general population in saudi arabia .\nchd in saudi arabia study found a high prevalence of htn ( 26% ) and diabetes ( 22% ) , together with a prevalence of chd of 6% , once again higher in the urban setting .\nurban location , age , male gender , bmi , htn , smoking , high serum cholesterol , and triglycerides were significant risk factors for chd.14 in a similar study carried out in jeddah in 2007 among university employees and school teachers estimated the prevalence of htn , smoking , dyslipidemia , and overweight to be 19.9% , 18.8% , 10.1% , and ~50% , respectively.15 a study at qassim university conducted in 2007 estimated the prevalence of low hdl was 73.6% and increased total cholesterol and triglycerides 60.0% and 46.4% , respectively.16 another study among attendees of a phc center in south - west region of saudi arabia found the prevalence of risk factors as follows : diabetes ( 28.2% ) , obesity ( 37.9% ) , and physical inactivity ( 68.3% ) .\nless than half of the study participants knew about these risk factors and their importance as preventive measures for noncommunicable diseases .\nknowledge of risk factors and prevention was significantly associated with educational level.17 a study in al - rabhwa phc center , riyadh in 2004 among diabetic patients found increased cholesterol ( 5.2\nhigh triglyceride ( 1.7% ) was 50% in both genders ; 13.4% of males were hypertensive as against 44.3% females .\nthere was no significant difference between risk factors for chd and duration of diabetes except that there were more smokers among those who had diabetes for < 10 years .\nmost of the diabetics with poor glycemic control ( fasting blood sugar > 8.3 mmol / l ) tended to be smokers , were more obese , had high triglyceride and high total cholesterol.18 the current focus of services at most phc centers and hospitals is curative , not preventive .\nhealth promotion and health education are currently mostly missing from the health - care system of saudi arabia .\nphc centers can fill this gap by providing health promotion and education programs , which have been found to play a significant role in improving lifestyle practices .\nthis could significantly reduce the burden of chronic noncommunicable disease.19 our study has a number of limitations .\nit was conducted in a university setting and so the results may not be generalized to the population .\nfurthermore , the study sample includes only those employees who opted for medical checkup , further restricting the generalizability of our results .\nthe health risk assessment relied on self - report . in our study , interviewing onsite might have caused limitation in the study as it might have resulted in underestimation in one or overestimation of the figures in other areas .\nit is emphasized that only those subjects , who were interested in knowing about their health status might have participated in the study resulting in overestimation of the general health status of the university employees .\nit was conducted in a university setting and so the results may not be generalized to the population .\nfurthermore , the study sample includes only those employees who opted for medical checkup , further restricting the generalizability of our results .\nthe health risk assessment relied on self - report . in our study , interviewing onsite might have caused limitation in the study as it might have resulted in underestimation in one or overestimation of the figures in other areas .\nit is emphasized that only those subjects , who were interested in knowing about their health status might have participated in the study resulting in overestimation of the general health status of the university employees .\nthe population risk for the development of chd in the coming decades is not trivial .\nshort - and long - term strategies are recommended to decrease the risk of chd and improve the quality of life .\nhealth education and disease promotion program as worksite wellness program is now recognized almost universally as an important intervention to reduce the occurrence and severity of diabetic complications , and also in reducing the delays to seek care when the first signs and symptoms of a complication are noticed by the patient .\nqassim university s employees worksite wellness program is already in place , although it needs to be up scaled and expanded to other universities in saudi arabia mandatory maintenance of a personal health profile , at within the campus clinic with periodic checkups linked with some incentives and gifts are some of the options that could also be used to combat with the situation .\nmoreover , the university also has the responsibility to develop interventions to be implemented at the community level . prevention research is needed to help design health promotion and disease prevention programs to be implemented through phc centers ; in this regard , a number of studies are already going on with assistance from qassim university s faculty .\nfurther research studies are required to find out the exact current status and how and what are the best available measures and strategies that can be adapted and could be found useful in combating the situation and improving the health status of the qassim university s staff .\nresearch studies at the community and mass scale level are also required to find out the current status of chronic diseases as risk factors for chd and the best behavioral modification , health educational , and other strategies to address the current situation in the general local population .", "answer": "objective : to estimate the risk profile of coronary heart disease ( chd ) among the staff members of qassim university and assess their knowledge in a screening campaign in qassim region , saudi arabia.methods:a cross - sectional study was conducted among male and female staff at qassim university campus . \n all employees of qassim university were invited to participate in the study . \n data were collected through a self - administered questionnaire . \n the study sample size was 233 staff and employees . \n the data were entered and analyzed using spss version 18 . the data analysis focused on providing point estimates for the risk factors.results:the study found that 30% of participants have one or more risk factors for chd , namely obesity 20.6% , diabetes 10.3% , hypertension 12.4% , dyslipidemia 10.7% , and smokers ( 11.6% ) . \n about 54% of the participants have a family history of at least one chronic disease as a risk factor for chd.conclusion:the most common risk factor of chd among the staff members is obesity by 20.6% . risk factors for chd are quite common among qassim university staff . these findings need to increase the health education and disease promotion program as an important intervention to reduce the occurrence and severity of chd risk factors and to improve the quality of the life of the staff members of qassim university .", "id": 782} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 50-year - old female occupational therapist with a history of laparoscopic anterior resection 4 years previously for a t1 n0 m0 recto - sigmoid adenocarcinoma was found to have an elevated serum carcinoembryonic antigen ( cea ) of 415.0 g / l on surveillance blood testing .\na computed tomography ( ct ) scan demonstrated a large mass in the left lobe of the liver involving the left and middle hepatic veins .\ncore biopsies demonstrated moderately differentiated adenocarcinoma , positive for ck20 , cea , and cdx2 and negative for ck7 , ttf-1 , and wt-1 , consistent with metastatic colorectal cancer .\nsince the liver lesion was potentially operable , a f - fluorodeoxyglucose - positron emission tomography ( pet)/ct scan was arranged to check for occult extra - hepatic metastases . the pet / ct demonstrated a left iliac bone metastasis , retroperitoneal lymphadenopathy and a f - fluorodeoxyglucose ( fdg)-avid thyroid nodule , reported as suspicious of malignancy ( figure 1 ) .\ngiven the presence of extra - hepatic metastases , the patient was treated with 6 months of palliative oxaliplatin and modified de gramont chemotherapy .\nalthough the possibility of a primary thyroid cancer was considered , in the context of inoperable metastatic colorectal cancer , further investigation of the thyroid abnormality was not considered appropriate at that time .\nct performed upon completion of treatment demonstrated partial response to chemotherapy : reduction of the liver metastasis , resolution of the retroperitoneal lymphadenopathy , and sclerosis of the right iliac bone metastasis .\nafter 3 months , she underwent left hepatectomy and cholecystectomy , followed by radiotherapy to the left ilium 2 months later .\nafter 2 years of follow - up , a ct scan demonstrated progression of the thyroid nodule and serum cea had risen to 2.2\nultrasound - guided fine needle aspiration of the thyroid nodule was graded thy5 with glandular malignant cells , which were negative for ttf1 and positive for cdx2 by immunocytochemistry .\nthis was consistent with metastatic colorectal adenocarcinoma , and , given that other disease sites had not changed over 2 years , the patient was offered a right hemi - thyroidectomy .\nthe patient is under ct and cea surveillance and remains in remission 10 months later with undetectable serum cea levels .\nalthough benign and malignant incidentalomas are rare in routine clinical practice,1 some clinicians have claimed that widespread use of whole - body imaging examinations has led to increased detection of thyroid \nincidentalomas2 two systematic reviews ( 55,160 and 125,754 subjects ) , analyzing studies using fdg / pet for various indications and patient populations , identified an incidence of focal fdg - avid thyroid lesions of 1%1.6%.3,4 malignancy was detected in 33%34.8% of those with follow - up data available , of whom 81.3%83% had papillary thyroid cancer ( ptc ) , in keeping with the overall proportion of thyroid cancers that are ptcs .\nof two studies reporting focal fdg - avid thyroid incidentalomas in patients with known or suspected nonthyroid malignancy , an incidence of 2.0%3.9% was reported , with 34.7%41.7% of these malignant lesions.5,6 in kim et al s study,6 all incidentalomas operated upon were identified as ptcs .\nthere has been a debate over the need to treat all ptcs . despite the threefold increase in the reported incidence of ptc over the last 3\ndecades,7 the death rate has remained stable.8 this is supported by the studies of active surveillance , which has not been associated with increased morbidity,9 and evidence of a significant burden of clinically occult ptc at autopsy.10 follicular , medullary , and anaplastic thyroid cancers carry worse prognoses and are considered to require intervention unless the patient has a very poor prognosis from the known nonthyroid malignancy .\na retrospective study of 47,813 thyroidectomies performed for various indications , identified thyroid metastases in 0.13% of samples.11 similar large data sets are not available for thyroidectomies performed only in patients with a known nonthyroid malignancy .\nmoreover , patients with thyroid metastases will typically have advanced malignancy and not proceed to thyroidectomy , so such data would underestimate the true incidence . in an autopsy series ,\nthe incidence was 1.9%24% in patients with known malignancy.12 cohort studies have suggested an association with renal cancer,13 although autopsy series indicate they are most commonly derived from lung , breast , and melanoma.12 this case emphasizes the importance of considering carefully whether or not to intervene when an incidental fdg - avid thyroid nodule is detected in a patient with metastatic cancer .\nappropriate investigation and management depend on the disease stage , patient s performance status , prognosis , and treatment plan for the known nonthyroid cancer , and whether or not the thyroid abnormality is symptomatic . if there are symptoms , ultrasound and fine needle aspiration for tissue diagnosis is warranted , and multidisciplinary team discussion involving an endocrine surgeon prior to considering further investigation and treatment\n. for asymptomatic patients , further investigation of fdg - avid thyroid lesions is only appropriate where demonstrating either metastatic disease to the thyroid or a more aggressive thyroid cancer will alter management strategy for that individual patient .\nthe patient in our report had inoperable metastatic disease , so the incidentaloma was not considered likely to affect clinical outcome . however , after the patient underwent potentially curative liver surgery and high - dose radiotherapy , and completed follow - up for 2 years , it became appropriate to further assess the thyroid lesion .\none study recruited 43 patients with metastases to the thyroid gland and reported a longer survival ( 34 vs 25 months ) for those undergoing surgery than in subjects treated nonsurgically.14 this was not replicated in another nonrandomized study of 36 patients with metastasis to the thyroid in which 21 patients received surgery versus 15 that did not.11 there was no statistical difference in overall survival despite the worse clinical situation of the nonsurgical cohort . therefore with such weak evidence available , in patients suitable for intervention for their incidentaloma ,\n surgery is generally the treatment of choice for solitary thyroid metastasis and for known thyroid metastasis in patients where other extrathyroid metastases are resectable.13 patients must be counseled regarding the 1%6% risk of surgical complications associated with thyroidectomy , including vocal cord paralysis , hypothyroidism , and hypoparathyroidism.2 in summary , fdg - avid thyroid nodules occur relatively frequently . on finding thyroid \nincidentalomas in patients with a history of cancer , metastasis should be considered , even though the majority of these lesions will be benign or ptc .\n incidentalomas must be seen in the context of the prognosis and treatment plan for the known malignancy .", "answer": "the routine use of 18f - fluorodeoxyglucose - positron emission tomography ( pet)/computed tomography scans for staging and assessment of treatment response for cancer has resulted in a large number of thyroid abnormalities being detected as incidental findings ( incidentalomas ) . \n since most pet / ct scans are performed in the setting of a known nonthyroid malignancy , the need for incidentalomas to be further investigated and managed depends on the stage , prognosis , and current treatment plan for the known malignancy . \n we present a case describing the management of an incidental f - fluorodeoxyglucose - avid thyroid nodule detected in a patient with known metastatic colorectal cancer . on the basis of this case \n , we discuss the management of incidental pet - detected thyroid nodules in patients with metastatic cancer . thyroid \n incidentalomas must be seen in the context of the prognosis and treatment plan for the known malignancy .", "id": 783} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe procedure included augmentation with transcortical wiring of an onlay - type prosthesis in twelve knees ( nine patients ) after it had been determined that conventional resurfacing was inadequate .\nthis technique was indicated when the thickness of the remnant patella was less than 8 mm and the cortical rim was not intact .\nthere were 9 patients ( 12 knees ) with a mean age of 68 years ( range , 53 to 80 years ) at the time of surgery .\nthe patellae were revised because of infection ( five knees ) , loosening of the patellar component ( four knees ) and polyethylene wear in the presence of a metal - backed patella ( three knees ) .\nan onlay - type , all polyethylene prostheses ( universal dome patella , scorpio , stryker , nj , usa ) which are compatible with the femoral component were used .\nafter arthrotomy using a medial parapatellar approach , the patella is everted laterally and fixed in this posture by grasping the quadriceps tendon or patella tendon with towel clips .\ncement stuck to the undersurface of the prosthesis is meticulously removed with an oscillating saw and a high - speed burr after implant removal . the new , properly sized patellar prosthesis\nis then placed on the undersurface , implant location is decided and the margin of the prosthesis and the contact points for each peg are marked .\nbone bed preparation is performed with a burr according to marking lines and contact points .\non fitting the patellar prosthesis , a check is made to determine whether it matches the concave portion of the undersurface and confirm the peg sites .\nthree points are then drilled for the pegs and bone holes are placed for wire passage .\nthe next steps involve connecting the wires to the pegs and passing through drill holes .\na wire is connected to one peg by winding it around the narrow part of the neck under the peg head and fixing it to the peg .\nthe three wires on the pegs are passed from the undersurface of the patella to the outer surface through the bone holes .\nbefore the prosthesis is brought into contact with the patella , the space between the bone bed and the polyethylene is filled with cement ( fig .\n2 ) . after approximating the patellar prosthesis to remaining bone as closely as possible ,\nthe prosthesis is compressed with a compressor and the cement is given time to harden .\nsubsequently , sufficient tension is placed on the three wires on the outer surface with wire holders and the wires are twisted together immediately above the cortex . after checking that the wires are under sufficient tension , they are cut and their ends are pressed with an impactor to prevent irritation ( fig .\nafter arthrotomy using a medial parapatellar approach , the patella is everted laterally and fixed in this posture by grasping the quadriceps tendon or patella tendon with towel clips .\ncement stuck to the undersurface of the prosthesis is meticulously removed with an oscillating saw and a high - speed burr after implant removal . the new , properly sized patellar prosthesis\nis then placed on the undersurface , implant location is decided and the margin of the prosthesis and the contact points for each peg are marked .\nbone bed preparation is performed with a burr according to marking lines and contact points .\non fitting the patellar prosthesis , a check is made to determine whether it matches the concave portion of the undersurface and confirm the peg sites .\nthree points are then drilled for the pegs and bone holes are placed for wire passage .\nthe next steps involve connecting the wires to the pegs and passing through drill holes .\na wire is connected to one peg by winding it around the narrow part of the neck under the peg head and fixing it to the peg .\nthe three wires on the pegs are passed from the undersurface of the patella to the outer surface through the bone holes .\nbefore the prosthesis is brought into contact with the patella , the space between the bone bed and the polyethylene is filled with cement ( fig .\n2 ) . after approximating the patellar prosthesis to remaining bone as closely as possible ,\nthe prosthesis is compressed with a compressor and the cement is given time to harden .\nsubsequently , sufficient tension is placed on the three wires on the outer surface with wire holders and the wires are twisted together immediately above the cortex . after checking that the wires are under sufficient tension , they are cut and their ends are pressed with an impactor to prevent irritation ( fig .\nif the patellar component can be retained during revision tka , this may offer the best option in terms of morbidity .\nhowever , if the prosthesis is malpositioned , damaged or mechanically loose , removal is probably the advisable option .\nthe onlay - type all polyethylene patellar prosthesis is an efficient tool when patellar bone stock is sufficient , being over 10 to 12 mm.5 ) but it is not easy to determine an optimal procedure if bone stock is poor . according to maheshwer et al.,2 )\npatellar resurfacing using an all polyethylene biconvex patellar prosthesis is successful when the remnant patellar thickness is less than 10 mm and the peripheral rim is intact .\nwhen the bone stock is too thin or the peripheral rim has been destroyed , it is highly likely to fail when a prosthesis is only cemented to bone .\na biconvex patellar prosthesis may also not be likely to be effective . in our series ,\nthe remnant patellar thickness averaged 5.6 mm ( range , 3.2 to 7 mm ) and variable amounts of the peripheral patellar rim were damaged . with regard to these cases , some authors advocated alternative options including a porous tantalum component , a bone grafting and soft tissue flap procedure or a gull - wing osteotomy .\nnelson et al.4 ) evaluated short - term results following patellar resurfacing with a trabecular metal patella in the setting of marked patellar bone loss .\nhanssen6 ) suggested a bone grafting and soft tissue flap procedure . at final follow - up of nine patients\n, it was found that the mean patellar thickness increased from 8 to19.7 mm and their functional outcomes were improved .\nklein et al.7 ) performed a gull - wing osteotomy in a nonresurfacable patella and reported that there was a significant improvement in the range of motion and knee society scores .\nthough several shortcomings were encountered during follow - up period , the above techniques showed reasonable outcomes.3,4,6,7 ) however , further follow - up is required to assess the longer term benefits of these methods .\nthe deficient patella was revised using this technique when the thickness of the remnant patella was less than 8 mm and the cortical rim was not intact .\nmoreover , it is easily reproducible and does not need a long learning curve , in our experience . because it protects the extensor mechanism and provides the same contact during patellofemoral articulation as primary tka , painless articulation is possible and\nhereby , the range of motion is improved . however , there are a few concerns about the use of this procedure in thin patellae .\nit may not be indicated if the osseous cortical shell is too thin for wiring , so the use of transcortical wires place the patella at risk to fracturing .\nalso , the problems related with prominent hardware also may occur as is oft en seen with internal fixation of patellar fractures . at a mean 10.3 months follow - up of our series , there was one patellar fracture arising during flexion exercise one week after surgery that was treated with partial patellectomy .\nour described technique includes connecting wires to the three pegs of the patellar component , passing the wires from the undersurface of the patella to the outer surface through the bone holes and , after compression of a cemented prosthesis , twisting the wires under sufficient tension .\nwe believe that this technique provides a good alternative option in managing the deficient patella in revision total knee arthroplasty , although any prolonged benefits will require long - term follow - up .", "answer": "the management of patellae with a severe bony deficiency during revision total knee arthroplasty is a challenging problem . \n however , using a technique of augmentation with transcortical wiring of an onlay - type prosthesis allowed the authors to revise a deficient patellae successfully . after making the decision to revise the existing patellar component , \n the procedure was found to be technically straightforward . \n furthermore , the procedure does not require sophisticated instruments , only an onlay - type prosthesis , cement and wires . \n this technique entails fixing wires to the three pegs of the patellar component , passing the wires through drill holes in the anterior cortex and , after compression of a cemented prosthesis , augmenting the fixation by twisting the wires anteriorly . \n we believe that stable fixation and painless articulation will be obtained with the described technique for deficient patellae .", "id": 784} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nobstructive sleep apnea ( osa ) is characterized by frequent episodes of termination of respiratory airflow caused by upper airway collapse during sleep , followed by oxyhemoglobin desaturation , persistent inspiratory attempts against the obstructed airway and arousals from sleep .\nthe inspiratory airflow can either decrease ( hypopnea ) or be completely absent ( apnea ) , and an apnea that lasts 10 seconds or longer , associated with ongoing ventilatory effort , characterizes a patient with osa .\nthe airflow limitation episodes are usually accompanied by decrease in hemoglobin level , which are usually terminated by quick micro - arousals as a result of excessive respiratory drive caused by the continuing hypoxemia [ 23 ] . to establish a definite diagnosis ,\nthe diagnosis of osa is confirmed when a person has an apnea / hypopnea index ( ahi : number of apneas and hypopneas per hour of sleep ) of more than five events per hour , associated with symptoms of excessive daytime sleepiness .\nalthough known to be a benign disease , numerous studies have shown that osa is usually correlated with increased morbidity and mortality because of cvd such as systemic and/or pulmonary hypertension as its most common consequence , heart failure , myocardial infarction and stroke [ 69 ] .\noxyhemoglobin desaturation - resaturation , which is common in osa patients , results in free radical production , release of proinflammatory cytokines and prothrombotic mediators and endothelial dysfunction and leads to sympathetic nervous system activity and increased blood pressure , as well as impairment of cerebrovascular auto - regulation .\ncontinuous positive airway pressure ( cpap ) has been shown to have cardio protective effects , decreasing mortality and morbidity among these patients [ 1214 ] .\nnumerous community - based studies have examined the relationship between osa and cvds [ 10 , 1821 ] .\nbased on these studies , age , gender , smoking status , bmi , ahi , total sleep time and day sleepiness were some of the clinically important predictors of cvd outcomes in osa patients .\nwe hypothesized that the ahi , currently used to determine the severity of osa , is not by itself enough to accurately predict cardiovascular outcomes in individuals with osa .\nwe also hypothesized that several factors such as patients demographic and clinical characteristics would have greater accuracy for predicting cvds . based on our electronic search ,\nthere is no published data about the prevalence of cvd among the iranian population with osa .\nour study aimed to resolve conflicting evidence on the impact of severity of osa , gender , age , bmi , smoking status and socioeconomic status on the association between osa and development of cvds .\nmedical files of 385 patients ( from 2009 to 2011 ) with definite osa , confirmed by overnight polysomnography were selected in noor sleep clinic , tehran , iran .\nparticipants were eligible if they only had osa ( not other types of sleep apnea such as central or mixed sleep apnea ) with ahi of equal or more than five events / hour .\ndemographic data were collected from patient files and included gender , age ( as reported by patients ) , smoking status and educational status ( last academic degree reported by patients ) .\nthree modes for smoking status were considered : never - smoker , ever - smoker and ex - smoker .\nbmi ( weight in kilograms divided by the square of height in meters ) and ahi ( events per hour ) were derived from the polysomnography reports .\nseveral questions were designed in a questionnaire to detect cvds such as presence of cvd , type of cvd and medications used .\nif there was any controversy in the answers , the patients were questioned about their disease status to clarify their health / disease state .\nthe data were analyzed using single regression analysis followed by multiple regression analysis ( by backward method ) to identify variables that were independently associated with cvd .\nthe majority of patients were males ( 71.9% ) . among the studied individuals , 26.5% showed at least one sign / symptom of cvd and hypertension was the most commonly reported sign ( 74.5% ) .\ndemographic characteristics and polysomnographic data of patients in cvd positive and cvd negative groups ( values are presented as meansd ) of patients , 17.9% had hypertension , 2.6% had coronary artery disease , 0.5% had arrhythmia and 0.3% had stroke ; 2.3% of the patients had both hypertension and coronary artery disease , 0.3% had both hypertension and history of myocardial infarction and 0.3% had both hypertension and history of stroke ; 0.8% of patients had myocardial infarction and one of them had hypertension as well .\nall variables had a significant association with cvd , except for smoking status ( p=0.77 ) .\nwe only selected variables with p - values less than 0.20 in simple regression analysis and entered them into the multiple logistic regression model .\nmultiple logistic regression analysis showed that the odds ratios for one grade increase in bmi and one year increase in age were 1.13 and 1.12 , respectively ( p<0.001 ) . in presence of these variables , severity of apnea ,\ngender and level of education ( as a socioeconomic index ) had no significant correlation with cvd ( p=0.36 , p=0.83 and p=0.79 , respectively ) .\nthis study provided information on the association between osa and cvds . in our osa population ,\n26.5% showed at least one sign / symptom of cvd , with hypertension being the most common sign ( 74.5% ) .\nwhile ahi was found to predict cvd in simple regression analysis , no significant association was found in multiple model adjusted for potential confoundders .\nmultiple regression analysis showed that aging and obesity were significant predictors of the occurrence of cvd in osa patients .\nlavie and lavie in a case - control study on seventy of osa showed that severity of osa affected biochemical markers associated with cvds only in severe stage and not mild or moderate stage of osa .\nshahar et al , in a cross sectional study also showed modest to moderate effects of sleep disordered breathing on various manifestations of cvds within a range of ahi values that were considered normal or only mildly upraised .\nkendzerska et al , in a decade - long cohort study showed that osa - related factors other than ahi were important predictors of composite cardiovascular outcome .\nour findings were in agreement with the afore - mentioned studies indicating that osa - related factors other than ahi ( bmi and aging ) are important predictors of cvds .\nthe mean of bmi in cvd+ group was calculated to be approximately 32 kg / m2 , which put them in obese group of bmi classification . in parallel with our study , dacal quintas\net al , found that the prevalence of osa in normal weight patients was lower than that in overweight and obese patients .\nseetho et al , reported that patients with osa and severe obesity had increased arterial stiffness , which would possibly affect cardiovascular risk independently of metabolic abnormalities .\ncarlson et al , showed that age , sleep apnea and obesity represented both independent and additive risk factors for development of systemic hypertension .\nsimilarly , lenfant described the correlation among obesity , hypertension and osa as a triangular relationship ; osa and obesity have an interactive relation and both of them have increasing effect on incidence of hypertension .\nour study showed that aging was another significant factor to explain the presence of cvd among osa patients .\npywaczewski et al , showed that the frequency of cardiovascular complications occurring in osa population increased with age .\nevidence has been inconsistent on the effect of gender on the association between osa and cardiovascular events . in our study , women with osa were more susceptible to develop cvd than men .\ndrummond et al , and quintana - gallego et al , found that women with osa had hypertension more frequently than men .\nfaulx et al , found that ahi was inversely associated with flow - mediated dilation and peak blood flow in women .\nin contrast , no relationship between ahi and flow - mediated dilation was found in men .\nthese results raise the possibility that women with sleep - disordered breathing are more vulnerable to related cvds than men .\non the other hand , mohsenin et al , showed that markedly obese men with osa may have a nearly two - fold greater risk for hypertension than women .\ngaines et al , showed that although women have naturally higher levels of inflammatory and metabolic markers than men , men with sleep apnea appear to have a more severe inflammatory profile compared to women .\nit is important to consider the role of bmi in this study and its conclusion : male sex is more susceptible for developing cvd only at the highest quartile of bmi . in a case - control study by lavie and lavie\n, a comparison was made between smoker and non - smoker patients with osa and they showed a significant interaction effect between smoking and severity of apnea on ceruloplasmin and high - density lipoprotein ( hdl ) levels .\nsmokers with severe sleep apnea had the highest level of ceruloplasmin and the lowest level of hdl .\nthey concluded that smoking and sleep apnea had a synergistic effect on some of the biochemical cardiovascular risk markers .\npatients with severe sleep apnea who smoked were at a greater risk for developing cvds than smokers with mild - moderate sleep apnea and patients who did not smoke .\nin our study , no significant correlation was observed between smoking and cvds ( p=0.77 ) .\none probable reason may be that most ex - smokers stopped smoking before doing the sleep test according to the doctor s advice . some studies categorized ex - smokers in the non - smoker group [ 3536 ] .\nbased on the electronic search , the current study is the first to provide comprehensive information about the role of severity of osa as a cause of cvd and its relationship with other important risk factors in an iranian population .\nwe included patients with a wide range of osa severity and a relatively large number of females .\nour findings are based on patients referred to a single center , which may reduce the generalizability of our findings .\nour study showed that ahi was significantly associated with cvd in simple regression analysis ; however , this association was not significant after controlling for other predictors .\nother osa - related predictors , such as bmi and age were significantly and independently correlated with increased risk of cvds , respectively . in presence of these variables , other phenotypic and socioeconomic factors like severity of apnea ,\nthus , health care providers should implement bmi control strategies and improve the quality of care for the elderly patients .", "answer": "objectives : obstructive sleep apnea ( osa ) can lead to various cardiovascular disorders ( cvd ) such as hypertension . \n there is no documented data about this relationship among the iranian population . \n the aim of this study was to obtain comprehensive information about the severity of osa as a cause of cvd and its relationship with other important risk factors.materials and methods : in this cross sectional study , we studied patients with osa and apnea / hypopnea index of 5 or more . \n the data were collected from the patients polysomnography report and medical files . \n data analysis was done with spss version 18.results:the majority of patients were males ( 71.9% ) . among the studied individuals , 26.5% showed at least one sign of cvd , and hypertension was the most common condition ( 74.5% ) . \n multiple regression analysis showed that the odds ratios for one unit increase in bmi and one year increase in age were 1.13 and 1.12 , respectively ( p<0.001).conclusions : in our study , bmi and age had the strongest relationship with cvd . \n thus , public health care providers should implement weight control strategies and improve diagnostic and treatment procedures for the elderly patients .", "id": 785} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nIodine(III) promotes cross-dehydrogenative coupling of N-hydroxyphthalimide and unactivated C(sp3)\u2013H bonds\n\nPaper sections:\nC\nross-dehydrogenation coupling (CDC), a type of chemical bond construction by direct dehydrogenation, has emerged as an important approach in chemical synthesis because of its excellent efficiency, atomic economy, and wide substrate scope [1][2][3][4] . Catalysts based on transition metals such as copper, iron, ruthenium, and manganese are typically used in CDC reactions [5][6][7] . However, issues associated with these metallic catalysts, such as high cost, harsh reaction conditions, toxicity, and metal residues, have restricted their application in organic synthesis 8,9 . Therefore, the development of efficient, simple, environmentally friendly, and metal-free CDC reactions has become a major trend 10 .
In 1985, the Masui group first applied N-hydroxyphthalimide (NHPI) as a metal-free oxidant to the oxidation of olefins via a free radical reaction 11 . The 'non-persistent' nitrogen-oxygen radical, i.e. phthalimide nitrogen-oxygen (PINO) radical 12 , is often used to activate inert hydrocarbon bonds due to its high activity 13 . Moreover, oxygen-substituted NHPI derivatives could be converted into alkoxyamines via hydrazinolysis 14 . Alkoxyamines can be further used to synthesize new cephalosporins, oxiconazoles, glucokinase activators, and other organic compounds with antibacterial activity [15][16][17] . Disadvantages of conventional synthetic methods for accessing these compounds include poor atom economy, tedious synthetic procedures, and unsatisfactory selectivity. Recent researches on the CDC reactions involving NHPI have focused mainly on activated C(sp 3 )-H bonds. Reaction sites are typically at benzylic positions or at the \u03b1 position of carbonyl moieties or ethers . The CDC reaction between NHPI and alkanes with inert C(sp 3 )-H bonds has rarely been studied, and only few examples have been reported so far (Fig. 1) [40][41][42][43] . For example, copper nitrate trihydrate-catalyzed functionalization of C(sp 3 )-H bonds adjacent to the oxygen atoms of ethers was realized with oxygen as the co-oxidant in 2017 37 . Functionalization either \u03b1to the oxygen atom of ethers or at the benzylic position of benzyl derivatives was accomplished with tetrabutylammonium iodide and tert-butylhydroperoxide under sonication 31 . It is noteworthy that the substrates in the previous reports did not involve acyclic alkanes or nitriles, and transition metal catalysts or superstoichiometric quantities of (volatile, toxic and explosive) tert-butylhydroperoxide were often required.
Hypervalent iodine can be used as an initiator to trigger various chemical reactions, functioning like a transition metal catalyst, and this reagent has been widely applied to drug synthesis and total synthesis of natural products [44][45][46][47][48] . Considering the potential value of R-ONH 2 compounds, we herein report an approach to constructing C-O bonds in unactivated alkanes, cyanides, ethers, and thioethers via a CDC reaction with NHPI in the presence of iodobenzene diacetate as a radical initiator (Fig. 1). The current method features a number of advantages, such as mild metal-free reaction conditions, high synthetic efficiency, environmentally friendliness, and applicability to a wide range of substrates.
\n\nResults and discussion\nReaction optimization. The project was commenced with the reaction of cyclohexane with NHPI at room temperature, in which the effect of oxidants [tert-butyl hydroperoxide (TBHP), PhI(OCOCF 3 ) 2 , H 2 O 2 , and PhI(OAc) 2 ] was investigated (Table 1, entries 1-5). The NHPI derivative 3 was formed in 40% yield only when PhI(OAc) 2 was applied as the oxidant (entry 5). The solvents [chloroform, water, N,N-dimethylacetamide (DMA), 1,2dichloroethane (DCE), acetonitrile (MeCN), ethyl acetate (EA), chlorobenzene (PhCl), dichloromethane (DCM), and benzene (PhH)] were next screened (entries 6-14). When PhI(OAc) 2 was used as the oxidant, DCM (entry 13) and benzene (entry 14) gave the best results. The reaction with PhI(OCOCF 3 ) 2 as the oxidant in DCM and PhH was then investigated, and the desired product 3 was obtained in 42 and 49% yield, respectively (entries 15, 16). The influence of the temperature (0 o C and 60 o C) on the reaction was examined with DCM as the solvent and PhI(OAc) 2 as the oxidant, and no better result was obtained (entries 17, 18). Notably, when DCM was used as the solvent, compound 4 was formed (15%) along with 3; the formation of 4 was obviously due to the reaction of the solvent molecule itself with NHPI (see Fig. 2 for the structure). The bond dissociation enthalpies (BDEs) for cyclohexane (cyclohexane-H) and DCM (DCM-H) were calculated by Gaussian 16 at B3LYP/6-31 G basis set level and found to be 402.3 and 416.5 kJ mol \u22121 , respectively, which indicates that cyclohexane should be slightly more prone to undergo this kind of reaction.
When the reaction was performed with DCM as both the solvent and the substrate, compound 4 was obtained in 50% yield (Fig. 2). Although no additional coupling products were produced when benzene was adopted as the solvent, considering the toxicity of benzene, DCM was chosen as the solvent for most of the subsequent experiments.
Substrate scope. The substrate scope was then explored under the optimal reaction conditions obtained (see Table 1, entry 15), and the experimental results are summarized in Fig. 3. First, the reactions of the cycloalkanes with NHPI were investigated. The C-O CDC reactions of cyclopentane, cycloheptane, and amantadine with NHPI proceeded smoothly and afforded compounds (5-7) in the yields of 55-85%. It should be mentioned that no reports have been disclosed concerning this kind of C-H activation for acyclic alkanes so far. The reactions of acyclic alkanes (e.g., n-pentane and n-hexane) with NHPI were then tested and inseparable oxidation products 8a/8b (1.7/1) and 9a/9b (1/2.4) were obtained, respectively, while single products were delivered from the reaction of 2,2-dimethylbutane and 2,2,4,4-tetramethylpentane in 48% (10) and 88% (11) yields, respectively. In these cases, no activation of the primary C(sp 3 )-H bond occurred. Further studies revealed that toluene, trimethylbenzene, p-nitrotoluene, p-chlorotoluene, 2-methylfuran, and 2-methylthiophene were suitable substrates as well, and the corresponding oxidation products (12-17) were afforded in 56-94% yields. The benzyl C(sp 3 )-H bond was involved in the CDC reaction for these substrates, and the chloro substituent on the phenyl ring does not affect the desired transformation essentially.
Cyano compounds play an important role in drug synthesis 49 , and several research groups have realised direct oxidation of \u03b1-C (sp 3 )-H in alkyl nitrile with metal catalysts 50,51 . Hence, alkyl nitrile substrates were next studied under the current transition metal-free conditions. For butyronitrile, isobutyronitrile, and pentonitrile, the corresponding \u03b1-C(sp 3 )-H bond oxidation products (18-20) were generated in the yields of 45-86%. The CDC reaction of various ethers and sulfides was also investigated. Cyclic ethers (21-23), acyclic ethers (24-30), thioethers (31-34), and even haloether (27) were converted into the corresponding oxidation products smoothly. Synthetic applications. A gram-scale reaction was performed to demonstrate the application of the current synthetic method. O-(Thiophen-2-ylmethyl) hydroxylamine is a key intermediate for the synthesis of new cephalosporins. The CDC reaction was scaled up to gram-scale with 2-methylthiophene as the substrate and compound 17 was obtained in 77% yield (Fig. 4). Alkoxyamine 35 was then obtained via hydrazinolysis of 17.
Relevant mechanistic studies were next performed (Fig. 5). The reaction of toluene (as the substrate) was found to be totally inhibited upon addition of 2,2,6,6-tetramethylpiperidinooxy (TEMPO), 2,6-di-tert-butyl-4-methylphenol (BHT), 2,2-diphenyl-1-picrylhydrazyl (DPPH), or Galvinoxyl. These results indicated that the current transformation might proceed via a radical reaction pathway.
A plausible mechanism is proposed for the current reaction (Fig. 6). Oxidation of NHPI (2) with PhI(OAc) 2 affords PINO radical 35 , which reacts with the substrate to form an alkyl radical via hydrogen abstraction. Finally, the alkyl radical couples with PINO radical to deliver the final product.
In conclusion, selective C-H functionalisation of alkanes remains a great challenge. PhI(OAc) 2 has been applied to mediating radical coupling of N-hydroxyphthalimide and unactivated C(sp 3 )-H bonds in a range of cyclic and acyclic alkanes. The present reaction was conducted at room temperature which was compatible with various solvents. A variety of cycloalkanes, acyclic alkanes, cyanides, ethers, and thioethers reacted smoothly with NHPI avoiding volatile, toxic and explosive reagents, providing a direct and simple access to O-substituted NHPI derivatives.
\n\nMethods\nGeneral Information. All experiments were conducted under air, using commercially purchased analytical reagents and solvents which do not require further purification. 1 HNMR and 13 CNMR spectra were recorded on a Bruker spectrometer (at 400 and 100 MHz, respectively). TMS was used as reference for chemical shifts. High-resolution mass spectrometry (HRMS) was recorded on an Agilent Technologies LC-TOF instrument. X-ray crystallography of compounds 4, 11, and 17 were performed on a Bruker Smart Apex CCD area detector diffractometer using graphite-monochromated Mo K\u03b1 radiation. The regards to the suitability and safety warnings of PhH: avoid contact with the skin, the eyes; wear suitable protective clothing, gloves, eye/ face protection; avoid release to the environment.
General procedure for the synthesis of R-ONH 2 compounds. PhI(OAc) 2 (2 mmol) and NHPI (1 mmol) were added to a solution of a substrate (2 mmol) in DCM (2 mL), and the reaction mixture was stirred at room temperature for 2 h and filtered. The filtrate was concentrated under reduced pressure to give a crude product, which was purified by flash silica gel column chromatography (petroleum ether/EtOAc, 50:1 to 20:1) to give the product.
Procedure for compound 35. Water (36 mL) and N-hydrazine hydrate (1.8 g, 54 mmol) were added to a solution of 2-(thiophen-2-ylmethoxy)isoindoline-1,3-dione (1.2 g, 4.63 mmol) in acetonitrile (50 mL). The mixture was stirred at room temperature for 4 h. The crude product was purified by flash silica gel column chromatography (petroleum ether/EtOAc, 5:1) to give the product (0.54 g, 91%) as a brown solid.
Reaction of Toluene with NHPI in the presence of radical trapping reagent. PhI(OAc) 2 (0.54 mmol), radical trapping reagent (0.54 mmol), and NHPI (0.27 mmol) were added to a solution of toluene (0.54 mmol) in DCM (2 mL), and the reaction mixture was stirred at room temperature for 2 h and detected by TLC.
", "answer": "Cross-dehydrogenative coupling reactions provide a method to construct new chemical bonds by direct C-H activation without any pre-functionalization. Compared to functionalization of a C-H bond \u03b1to ether oxygen, \u03b1to carbonyl, or at a benzylic position, functionalization of unactivated hydrocarbons is difficult and often requires high temperatures, a transition-metal catalyst, or a superstoichiometric quantity of volatile, toxic, and explosive tert-butylhydroperoxide. Here, a cross-dehydrogenative C-O coupling reaction of Nhydroxyphthalimide with unactivated alkanes, nitriles, ethers, and thioethers has been realized by using iodobenzene diacetate as the radical initiator. The current protocol enables efficient functionalization of unactivated hydrocarbons and nitriles through inert C(sp 3 )-H bond activation under mild reaction conditions. O-substituted NHPI derivatives are generated in good yields under metal-free conditions.", "id": 786} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nureteropelvic junction obstruction ( upjo ) in children most commonly occurs due to adynamic segment of ureter .\npreviously , ureteral polyp causing upjo in children has been reported in as low as 0.5% of pyeloplasties in children.1 however , in recent studies the incidence reported was around 5%.2 \n 3 \n 4 \n 5 as li et al mentioned in their report , authors are unsure on whether it is due to more careful patient data documentation or it is about the increase of incidence.5 \n fibroepithelial polyps are more common in boys than girls.1 \n 2 \n 3 \n 4 \n 5 it is predominant at the left side in up to 70% of the patients.1 \n 6 \n 7 moreover , bilateral cases were reported as well.8 even if many phenotypes of fibroepithelial polyp ( fep ) were defined , there is no consensus on etiology such as chronic irritation , infections , hormonal imbalance , allergy , or developmental defects.9 \n 10 \n hydronephrosis with ureteral polyp requires surgical treatment , due to the risk of malignity1 \n 11 and obstruction .\nexcision of the polyp can be performed by laparoscopy , retroperitoneoscopy , transurethral ureteroscopy , or percutaneous access.12 \n 13 \n 14 \n 15 \n 16 \n 17 overall , kojima et al described performing endoscopy via a working port while laparoscopic exploration.4 \n in this case report , we present laparoscopic technique in a patient who had ureteral polyp close to the left upj .\na-10-year old boy was admitted at our pediatric emergency department with complaints of abdominal pain and vomiting . in his medical history , he had episodes of abdominal pain without hematuria or urinary tract infection .\nthe abdominal pain was located on the left upper abdomen and lumbar region . although previous ultrasound reports revealed only mild hydronephrosis , the last one showed hydronephrosis related to a polyploid lesion , which was located near upj and protruding into the proximal left ureter ( fig .\n1 ) . a tc diethylenetriamine pentaacetic acid ( dtpa ) renography revealed nonobstructive hydronephrosis with late drainage after diuretic injection .\numbilical 10 mm optic port ( 10 mm reusble port , karl storz gmbh & co. kg ) and two 5 mm ( disposable ) working ports , one on the epigastric region and the other on the left lower quadrant were introduced\n. pneumoperitoneum was created at a pressure of 13 mm hg with the flow of 3.5 l / min .\ntransmesocolic laparoscopic exploration showed a protruding mass on upj and hydronephrosis ( figs . 2 and 3 ) . following the transmesocolic dissection of upj\n, a stay suture passing through the abdominal wall was placed to keep the left ureter hanging .\npelvis , close to the upj , was incised and a cauliflower - shaped polyp that was about 20 mm in diameter with a wide base protruding ( fig .\nexcision of the mass was performed including the regions of pelvis and ureter close to the mass ( fig .\ndismembered pyeloplasty was performed with interrupted 50 polydioxanone sutures and double j stent was placed .\nthe total operative time was 200 minutes , with an estimated operative blood loss of 20 ml .\nafter a follow - up of 2 years , patient did well with normal dtpa renography . \n\nfeps of the ureter are of mesoderm origin , rare benign tumors in children.18 they may arise in any location from renal pelvis to the urethra in the order of decreasing frequency.19 on the other hand , feps may have varied sizes and shapes .\nthey might be 1to 50 mm long or have shapes such as pedunculated with a smooth surface or with multiple finger - like projections.1 \n 10 \n 20 \n 21 age of the patient , structural features of polyps , and experience level of the surgeon determine treatment preferences and consequences of surgery .\nhowever , although there are few studies , transitional cell carcinoma arising from fibroepithelial polyp and recurrence due to incomplete resection has been reported.11 \n 22 on the other hand , adey et al stated in 2003 that only 22% of feps were diagnosed preoperatively and li et al mentioned in 2014 that none of the feps in their study were detected before surgery.1 \n 5 in our case , fep was detected after a follow - up of 4 years .\nso we believe the delay in diagnosis might be due to intermittent obstruction and slow growing nature of polyp .\nalthough malignity , recurrence , and any other associated polyp is extremely low , surgeon should ensure not to leave remnant of feps during excision . in the past ,\nopen surgery was the only option , however , recently minimal invasive approaches have been recommended in children and adults.4 \n 13 \n 14 \n 15 \n 23 furthermore , several authors have described their successful experience in using holmium laser resection , percutaneous , and/or ureteroscopic approaches in the treatment of feps.13 \n 14 \n 15 conversely , sun et al figured out in their study that strictures might be cause of over vaporization and kiel et al mentioned the risk of recurrence due to incomplete resection of tumor.4 \n 15 \n 24 bartone et al speculated that resecting the polyp without base might cause obstruction and recurrence.25 on the other hand , adey et al underlined the importance of dismembered pyeloplasty whereas polyps might have been missed , if spiral flap or y v pyeloplasty is performed.1 moreover , iwatsuki et al and tsuzuki et al published their successful laparoscopic treatment of fep either in child and adult patients.16 \n 26 \n since fep was located close to upj , we preferred to perform laparoscopy .\nit should be noted that , despite postoperative controversies of endoscopic resection or fulguration of a wide base polyp ; local resection , fulguration , or pyeloplasty can be performed easily during laparoscopic approach .\nthe overall laparoscopic exploration shows the exact location and size of the polyp , neighboring organs , and structures .\nluminal mucosal evaluation with exposure of proximal and distal resection margins could be performed well with optic magnification .\nthere are several options for laparoscopic approach to renal pelvis and upj region on the left side .\ndepending on the patient and experience of the surgeon retroperitoneoscopy , transabdominal retrocolic or transmesocolic approaches can be performed.12 \n 13 \n 14 \n 15 \n 16 \n 17 to our knowledge , in pediatric age group , retroperitoneoscopy and endoscopy may not provide enough surgical working space .\nso we suggest transabdominal transmesocolic approach and believe that exploration and surgical manipulation might be easier compared to retroperitoneoscopy or endoscopy .\npediatric surgery is a specialty that has its own characteristics owing to relevance of congenital anomalies .\ntime to time , it is hard to estimate the real anomaly although advanced diagnostic tools are in use , as was in our case . and to me\n, a pediatric surgeon should be always alert , for concomitant pathologies , in any anomaly .\nbesides open access , both endoscopic or laparoscopic approaches should be in practice of surgeon , for being minimally invasive .", "answer": "fibroepithelial polyps are a rare underlying reason of ureteropelvic junction obstruction . in the past , open surgery was the only option . however , \n due to development of minimal invasive technics , treatment alternatives have been changed . \n resection by laparoscopy or endoscopy , laser fulguration and/or percutaneous resection are recommended in children and adults . \n here , we present a 10-year - old boy with severe left hydronephrosis due to fibroepithelial polyp close to the ureteropelvic junction and our laparoscopic approach .", "id": 787} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe penn diabetes heart study ( pdhs ) is an ongoing , cross - sectional study of individuals with type 2 diabetes ( aged 3575 years ) without clinical evidence of cvd ( myocardial infarction , coronary revascularization or angiographic disease , positive stress test , clinical peripheral arterial disease or peripheral arterial revascularization , stroke , or transient ischemic attack ) .\nthe university of pennsylvania institutional review board approved the study protocol , and all subjects gave written informed consent ( 4 ) . the ankle - brachial index ( abi )\nwas calculated by dividing the average of the ankle pressures by the highest brachial pressure .\nparticipants with an abi > 1.4 ( n = 13 ) reflecting noncompressible arteries were excluded ( 5 ) .\neach subject had the estimated glomerular filtration rate ( egfr ) calculated based on the abbreviated modification of diet in renal disease study equation ( 6 ) .\nplasma levels of fetuin - a ( 4.3 and 10.2% , respectively , intra - assay and inter - assay coefficient of variation ) were measured by enzyme - linked immunosorbent assay ( biovendor laboratory medicine , modrice , czech republic ) .\nhigh - sensitivity c - reactive protein ( hscrp ) was measured by immunoturbidimetric assay ( wako , osaka , japan ) .\nstudent 's t test was used for normal continuous variables and the kruskal - wallis for nonnormal distributed variables .\nthe association between a 1-sd change in fetuin - a and pad was examined using unadjusted and multivariable adjusted logistic regression models as described in table 1 .\nanalyses were performed on stata 10.0 software ( stata , college station , tx ) .\nassociation between fetuin - a and pad data are odds ratios ( 95% ci ) and were obtained by logistic regression model .\nmodel 2 : model 1 + smoking , hypertension , hypercholesterolemia , metabolic syndrome , a1c , framingham risk score ( % ) , and medications ( ace inhibitors , aspirin , statins , insulin , metformin , sulfonylureas , and thiazolidinediones ) .\nthe ankle - brachial index ( abi ) was calculated by dividing the average of the ankle pressures by the highest brachial pressure .\nparticipants with an abi > 1.4 ( n = 13 ) reflecting noncompressible arteries were excluded ( 5 ) .\neach subject had the estimated glomerular filtration rate ( egfr ) calculated based on the abbreviated modification of diet in renal disease study equation ( 6 ) .\nplasma levels of fetuin - a ( 4.3 and 10.2% , respectively , intra - assay and inter - assay coefficient of variation ) were measured by enzyme - linked immunosorbent assay ( biovendor laboratory medicine , modrice , czech republic ) . high - sensitivity c - reactive protein ( hscrp )\nstudent 's t test was used for normal continuous variables and the kruskal - wallis for nonnormal distributed variables .\nthe association between a 1-sd change in fetuin - a and pad was examined using unadjusted and multivariable adjusted logistic regression models as described in table 1 .\nanalyses were performed on stata 10.0 software ( stata , college station , tx ) .\nassociation between fetuin - a and pad data are odds ratios ( 95% ci ) and were obtained by logistic regression model .\nmodel 2 : model 1 + smoking , hypertension , hypercholesterolemia , metabolic syndrome , a1c , framingham risk score ( % ) , and medications ( ace inhibitors , aspirin , statins , insulin , metformin , sulfonylureas , and thiazolidinediones ) .\namong 738 subjects in the study sample , pad prevalence was 5.1% , the mean age was 58.7 9.3 years , 37.1% were female , 63.2% were caucasians , and 32.1% were african americans .\nthe median fetuin - a level was 292.4 ng / ml ( interquartile range 115.5 ) . individuals with pad had a significantly lower fetuin - a level compared with individuals without pad ( 269.3 vs. 293.4 , p < 0.001 ) .\nno significant differences were noted in other cardiovascular risk factors , metabolic syndrome , kidney function , inflammation , bmi , serum albumin ( the only surrogate marker of liver function collected on the pdhs ) , or medication use .\nfetuin - a levels decreased consistently ( p for trend < 0.02 ) across abi clinically relevant cut points ( < 0.7 , 0.70.9 , 0.91.1 , and 1.11.4 ) ( 7 ) ( see supplemental fig . 1 in the online appendix [ available at http://care.diabetesjournals.org/cgi/content/full/dc09-1541/dc1 ] ) . the odds of pad were significantly increased for each sd decrease in fetuin - a ( odds ratio 1.6 [ 95% ci 1.12.3 ] , p = 0.001 ) and the association persisted in incremental models that adjusted fully for age , sex , race , kidney function , cardiovascular risk factors , medication use , and hscrp ( 1.6 [ 1.0582.5 ] , p = 0.03 ) ( table 1 ) .\na similar trend was noted among subjects with egfr > 80 ml min 1.73 m ( 1.9 [ 1.03.4 ] , p = 0.05 ) , suggesting that our findings were not confounded by the presence of moderate kidney disease .\nfinally , in a fully adjusted subgroup analysis , participants with hscrp levels <3 mg / dl ( n = 460 ) had higher odds of pad ( 2.6 [ 1.45.0 ] , p = 0.002 ) , whereas subjects with high hscrp levels ( 3 mg / dl ; n = 234 ) did not ( 0.82 [ 0.41.6 ] , p = 0.59 ) .\nlow levels of fetuin - a have been linked to medial arterial calcification and flow limiting aortic stenosis in humans ( 8,9 ) . in this study , we demonstrate that lower levels of fetuin - a are associated with pad in subjects with type 2 diabetes . to our knowledge , this is the first study to report such a relationship in the absence of advanced kidney disease or prevalent cvd .\nnotably , in analysis stratified by the centers for disease control and prevention / american heart association defined hscrp risk strata ( 10 ) , fetuin - a conferred increased odds of pad in subjects with hscrp <3 mg / dl and also in participants with interleukin ( il)-6 levels below the median ( data not shown ) .\nthis is consistent with studies reporting an increased cvd risk mortality with fetuin - a deficiency independent of hscrp and il-6 ( 11 ) and points to a unique role for this negative acute - phase protein as a biomarker of pad beyond traditional and novel cardiovascular risk factors . remarkably , animal models appear to track with our clinical observations . in mice lacking the fetuin - a gene ,\nthe aorta was found to be spared of calcification and fibrosis , whereas peripheral vessels in the skin and kidney showed evidence of extensive calcification ( 2 ) , and the small artery involvement preceded the renal impairment ( 3 ) . however , in the absence of direct imaging data , we are unable to define the type of vascular phenotype ( intimal calcification or medial calcification ) that account for the observed association .\nan abi of < 0.9 is 95% sensitive and 99% specific for a stenotic lesion ( > 50% ) ( 12 ) .\ntherefore , we assume that some degree of eccentric atherosclerotic calcification contributes to the association observed while acknowledging that multiple types of vascular calcification may coexist in type 2 diabetes ( 13 ) . nonalcoholic liver disease and other phenotypes related to insulin resistance , including type 2 diabetes ( 14 ) , are associated with higher levels of fetuin - a ( 15 ) .\nwe controlled for most potential confounding factors and found no attenuation of the inverse association of fetuin - a with pad .\nin particular , because of this inverse relationship , a significant confounding effect was not expected by any condition associated with high fetuin - a levels .\nfinally , our study is limited by cross - sectional design , which limits causal inferences . in summary ,\nlow plasma fetuin - a levels are associated with pad in type 2 diabetes independent of traditional and contemporary risk factors .\nour findings suggest a unique role for fetuin - a deficiency as a biomarker of pad in the setting of type 2 diabetes .", "answer": "objectivefetuin - a is an inhibitor of vascular calcification and a mediator of insulin resistance . \n this study evaluated the association of plasma fetuin - a and peripheral arterial disease ( pad).research design and methodsa total of 738 individuals with type 2 diabetes ( mean age 58.7 years , 37.1% female ) without known cardiovascular or kidney disease were included in this cross - sectional analysis.resultssubjects with pad had a significantly lower fetuin - a ( 264.3 vs. 293.4 ng / dl , p < 0.001 ) . in multivariable analysis , a 1-sd decrease in fetuin - a increased the odds of pad ( odds ratio 1.6 , p = 0.02 ) . \n subgroup analysis revealed an increased odds even in subjects with glomerular filtration rate > 80 ( odds ratio 1.9 , p = 0.05 ) or high - sensitivity c - reactive protein <3 mg / dl ( odds ratio 2.7 , p = 0.002).conclusionslower circulating fetuin - a is associated with pad in type 2 diabetes beyond traditional and novel cardiovascular risk factors . \n our findings suggest a potentially unique role for fetuin - a deficiency as a biomarker of pad in patients with type 2 diabetes .", "id": 788} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nneurofibromatosis affects 1:3,000 individuals , and characterized by largely benign but often debilitating tumors that grow in the nervous system .\nits course is unpredictable : it can cause a variety of benign nerve tumors including plexiform , dermal , and optic glioma tumors ; in some cases malignant peripheral nerve sheath tumors can develop in the plexiform tumours .\ndown 's syndrome is one of the most common and easily recognized genetic conditions in humans .\nthe estimated prevalence in the united states is approximately 15 per 10,000 live births ( ie , 1 out of every 700 )\nmost often , it is the result of nondisjunction on chromosome 21 during maternal meiotic division .\nwe herein present the case of a 17-year - old boy with complaints of skin lesions over the back associated with mild itching since 3 months .\nhe was a known case of down 's syndrome with a history of seizures in childhood [ figure 1 ] .\nthe lesions gradually increased in size and number , and similar lesions started developing over his forehead since 23 weeks . on examination , multiple skin colored papules of varying size were present over the entire back and the forehead .\nvelvety thickening of the skin and hyperpigmentation of the axillae suggestive of acanthosis nigricans was present .\nthe characteristic features of down 's syndrome , including simian crease , mongoloid facies , and mental retardation were present .\ncanities and a solitary keloid over the chest were also seen apart from the clinical features of down 's syndrome . on oral examination , scrotal tongue , abnormal dentition , and\nother investigations such as ct scan brain , 2d echo , and ecg were normal .\nhistopathology of the nodule from the back revealed focally thinned out epidermis with intact basal layer ; the papillary dermis showed a mild perivascular infiltrate .\ndeeper dermis showed a benign spindle cell proliferation suggestive of neurofibromatosis [ figure 3 ] .\nphysical appearance of down 's syndrome ( a ) neurofibromas ( b ) sebaceous cyst ( c ) acanthosis nigricans , and axillary freckling ( d ) scrotal tongue focally thinned out epidermis with intact basal layer with the papillary dermis showing a mild perivascular infiltrate .\nthe presentation of a patient with two unrelated genetic disorders is uncommon , although not statistically impossible .\nhowever , in two of these reports , a third medical condition was also present . in one report , breast cancer was reported . in the other ,\nour patient had down 's syndrome , neurofibromatosis , dental anomalies , and ocular defects and keloids . in the large majority of cases , trisomy 21\nthere is no current evidence to support the idea that this is anything other than a chance occurrence .\nthe two conditions are not related , and the likelihood of a person being born with these two conditions is approximately 1 in 2,700,000 births .\nthey however overlap in their manifestations . both are associated with intellectual impairment to differing degrees .\nmacroglossia occurs in both conditions , as may facial , dental , and occlusal abnormalities .\nhearing and speech are affected in both conditions , as may the ability to maintain an acceptable level of oral hygiene .\nmutations in the gene results in abnormal control of cell growth , differentiation , and aberrant myelination . our patient with of neurofibrmatosis type 1 with down 's syndrome is the first such to have a keloid and sebaceous cyst apart from myopia and dental anomalies . the unpredictable nature and course of the two genetic disorders along with multiple acquired conditions in this patient make it difficult for patients , teachers , care givers , and medical / dental providers to create and maintain long - term care plans . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .\nthe authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )\nhas / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .\nthe patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .", "answer": "we report a patient with down 's syndrome and neurofibromatosis who presented with a keloid , sebaceous cyst and acanthosis nigricans , along with dental and ophthalmological defects . \n the coexistence of neurofibromatosis type 1 and down 's syndrome which are two unrelated genetic conditions is itself a rarity .", "id": 789} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe describe a case of pseudotumor cerebri in a young man developing 4 years post - traumatic brain injury ( tbi ) .\nthis is a rare clinical scenario and delayed presentation following tbi with chronic headaches should raise this possibility .\ndetailed clinical history and examination with appropriate investigations must be performed to diagnose this condition .\na 29-year - old male was admitted to our unit with head injury following a road traffic accident .\nhis glasgow coma score was 15/15 at admission and had no neurological deficits on examination .\nct brain showed small right frontal extradural hematoma with associated pneumocranium , right orbital roof , and cribriform plate fracture .\na repeat ct brain scan revealed an increase in the size of the extradural hematoma following which he underwent a frontoparietal craniotomy and evacuation of the extradural hematoma .\nhe recovered well postoperatively and was discharged home . since discharge , he experienced intermittent frontotemporal headache and worsening of short - term memory .\nfive months later , he developed a right - sided facial swelling and erythema , with frontal headache , fever , and episodes of vomiting .\nremoval of infected bone flap was performed , and staphylococcus aureus was isolated from the bone flap .\nhis headache persisted following treatment , and he had no signs suggestive of raised intracranial pressure .\nhe remained well for the next 12 months apart from episodes of headaches on and off .\na lumbar puncture was performed after imaging and was noted to have an elevated csf pressure of 20 mmhg and a diagnosis of pseudotumor cerebri was made .\nhe underwent a lumbar - peritoneal ( lp ) shunt and postoperatively his symptoms improved transiently over the next few weeks .\nhe had gained 9 kg of weight over the course of 4 years .two months subsequent to lp shunt insertion , he presented with worsening headaches and a new lumbar puncture showed an opening pressure of 25 mmhg , and closing pressure of 8 mmhg with no evidence of csf infection .\nct brain revealed no evidence of increase intracranial pressure , and a right ventriculo peritoneal ( vp ) shunt was inserted .\nhis headache persisted following vp shunt insertion and subsequent to this he underwent bitemporal decompression ( craniectomy ) in 3 weeks time with the removal of lp shunt [ figure 1 ] .\nhe had two further vp shunt blockages and he developed a slit ventricle syndrome despite the shunt malfunction [ figure 2 ] .\na ct venogram was performed 1 year later , which demonstrated a stenosis of the left transverse sinus and sigmoid sinus with hypoplastic right transverse and sigmoid sinuses .\nthe cerebral venous pressure was measured with significant left transverse sinus stenosis , and pressure gradient of 2612 mmhg , > 50% gradient .\nthis was managed nonoperatively , and it was found not to contribute to his on - going symptoms . he was also commenced on acetazolamide for the management of pseudotumor cerebri .\nct brain demonstrating bitemporal decompressive craniectomy ct brain with vp shunt in situ and slit - ventricle with an underlying shunt malfunction\npseudotumor cerebri is more commonly seen in young obese women than men . in a study by durcan et al .\ndetermining the incidence of pesuedotumor cerebri in iowa and louisiana , it was noted that obesity increased the incidence in both males and females with a overall female - to - male ratio of 8:1 .\npseudotumor cerebri is a relatively common neurologic illness and may be an important preventable cause of blindness in obese young women .\npseudotumor cerebri usually presents in adults with transient visual obscuration and blurred vision in contrast to development of diplopia in the pediatric age group .\nvarious clinical conditions and factors are associated with development of pseudotumor cerebri . in our case\nwe focus on the possible etiology following tbi and have attempted to outline the possible causes for the development of pseudotumor cerebri .\nthe question then arises as to why all the patients with tbi do not develop pseudotumor cerebri .\nthe mechanism of csf flow dynamics alteration following central nervous system infection and cerebral blood flow alteration is usually seen during the period of insult to the brain and transient alteration in the physiology is a reversible phenomenon depending on the severity of head injury .\nthe pathological process reverts to normal and very rarely , as in this case , may lead to the development of pseudotumor cerebri .\npossible etiologies contributing to pseudotumor cerebri mastoiditis and subsequent venous thrombosis is a known to cause pseudotumor cerebri , and there was no evidence of sinus thrombosis on imaging in our case .\nthe bone flap infection may have altered the cerebral venous drainage and subsequently caused changes in the csf slow dynamics .\nthe patient had gained weight following the head injury , and weight gain and obesity are important etiological factors in the development of pseudotumor cerebri .\nthe management was aimed at preventing the possibility of optic nerve damage and blindness in benign intracranial hypertension ( bih ) , vp shunt , and lp shunt are the surgical options available for pseudotumor cerebri and our patients visual symptoms got better following csf diversion procedures .\nwe experienced the difficulty in managing the patient in the later stage due to shunt dysfunctions with associated slit - ventricle syndrome .\nthis procedure was resorted to , as a last option for controlling headaches and it is known to be effective in symptomatic control in the some group of patients described in the literature . the prognosis for vision in most patients with pseudotumor cerebri is excellent ; however , visual loss , which is the only serious complication , may occur either early or late in the course of the disease .\nwhen a post - head injury patient presents with history of chronic headache with visual disturbance , pseudotumor cerebri should be considered a strong possibility .\nneuroimaging in the form of brain ct , mri , and mr venogram must be considered to rule out vascular pathology and a diagnostic lumbar puncture is recommended .\ncsf flow diversion techniques must be adopted to treat this condition , and these may require long - term follow - up .", "answer": "we describe a case of pseudotumor cerebri in a young man developing 4 years post - traumatic brain injury ( tbi ) . a 29-year - old man was admitted after sustaining a fall with headache , and no clinical deficits \n were noted on examination . \n ct brain demonstrated an extradural hematoma . \n this was successfully evacuated after his symptomatic worsening . following this , he developed bone flap infection and had the infected bone flap removed . \n he developed chronic mild - to - moderate headache following these procedures , which failed to respond to medical treatment . \n pseudotumor cerebri was diagnosed . \n a lumboperitoneal ( lp ) shunt , ventriculo - peritoneal ( vp ) shunt , and bitemporal craniectomy were performed as a part of management at different stages . \n post - tbi patients may present with chronic headache and in such circumstances , a possibility of pseudotumor cerebri must be considered . \n investigations should include neuroimaging in the form of mri / mrv and fundoscopy to look for papilledema . \n management in the form of csf flow diversion techniques ( vp and lp shunt ) with medical management results in good clinical outcomes", "id": 790} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nMechanistic Insight Leads to a Ligand That Facilitates the Pd-Catalyzed Formation of 2-(Hetero)Arylaminooxazoles and 4-(Hetero)Arylaminothiazoles\n\nPaper sections:\n\nPalladium catalyzed C\u2013N bond-forming reactions have impacted the synthesis of nitrogen-containing molecules in a range of scientific disciplines1, including materials science2, chemical biology3 and medicinal/process chemistry4. Insights into the mechanism of the reaction have informed the development of better ligands and reaction conditions, resulting in C\u2013N cross-coupling protocols of substantial utility and generality.5 Nevertheless, important limitations to the scope of the reaction remain, especially with respect to the coupling of highly functionalized or heterocyclic substrates, which are of particular relevance to the synthesis of biologically active compounds.6 Indeed, medicinal chemists at Merck recently disclosed that 55% of the metal-catalyzed C\u2013N cross-coupling reactions performed at their facilities failed to deliver any desired product in late stage synthesis of drug leads, highlighting some of the persistent barriers to overcome in the development of this transformation.7
The cross-coupling of five-membered heteroarylamines with aryl halides remains challenging in many cases despite their frequent occurrence as substructures of natural products8, pharmaceuticals and other biologically active molecules.9 For example, researchers at AstraZeneca recently reported their difficulties in developing conditions for the palladium-catalyzed cross-coupling of 2-aminooxazoles.10 The authors reported that only trace amounts of coupling product could be obtained in the case of the parent 2-aminooxazole (1), although a handful of 4- and 5-substituted derivatives could be coupled in low to moderate yield. To prepare the coupling product of 1, a multistep procedure involving the saponification and decarboxylation of the 4-ethylester derivative was required. In general, improvements in the cross-coupling of five-membered heteroarylamines, such as 2-aminooxazole 1, would be a useful advance for the field of transition metal-catalyzed cross coupling.
We previously reported BrettPhos11 (Figure 1b/2a, L1) as an effective supporting ligand for selective monoarylation of primary amines catalyzed by palladium.4b,12 The methoxy substituentat the C3-position (Figure 1b) has been found to play an important role in the selectivity and reactivity of catalysts supported by this ligand.11a, 13 Reductive elimination studies have demonstrated that BrettPhos-supported palladium(II) complexes will reside as the O- and C-bound isomers (Figure 1b), and the O-bound isomer is less competent for reductive elimination. We thus hypothesized that the O-bound complexes may be \"off-cycle\" palladium intermediates that must be eventually converted to the product-producing C-bound complex (IV). We felt that the development of a ligand that favored C-bound isomers might enable a catalyst system with improved reaction rates and efficiencies for challenging substrate classes.
With this hypothesis in mind, we synthesized an array of L1 analogues that we believed could decrease the percentage of the O-bound isomer. This study (detailed in the supporting information) led to the identification of EPhos (L3) as an effective ligand for the cross-coupling of 1 with an array of hindered and/or functionalized aryl chlorides and bromides, as well as commercial pharmaceuticals. In addition, the catalytic system was used to prepare several functionalized 4-(hetero)arylaminothiazoles. Studies that employed reaction calorimetry and NMR implied that reactions with palladium catalysts based on L3 show improved reaction rates and the resting state of the catalystis solely as the C-bound isomer.
The results in Figure 3 show the improved reactivity observed with L3-based palladium catalysts. The cross coupling of 2-aminooxazole 1 with 3-chloropyridine (2a) and 2,6-dimethylchlorobenzene (2b) was examined with a range of ligands and reaction conditions. A series of precatalysts14 based on BrettPhos (P1), tBuBrettPhos (P2), EPhos (P3), and XPhos (P4) as the supporting ligands were evaluated in the presence of either NaOPh (Conditions A) or K2CO3 (Conditions B), and it was determined that the use of P3 provided the highest yields for either pair of starting materials (see the supporting information for the full set of details for this study). P1\u2013P3 each afforded product with 3-chloropyridine (2a), while no product was obtained using P4, highlighting the importance of the 3-alkoxy substituent in the ligand structure. In the case of 2,6-dimethylchlorobenzene (2b), P2 was found to be ineffective, presumably due to the combined steric hindrance from the ligand and the aryl chloride.
With two sets of conditions (Conditions A and B) employing P3 as the precatalyst, the scope of the cross coupling of aminooxazole 1 was explored with a wide variety of aryl chlorides and bromides. When relatively simple and unhindered aryl halides were employed, precatalysts based on BrettPhos (P1) and EPhos (P3) performed comparably. However, when the cross coupling of more complex or sterically hindered substrates was attempted, significantly better yields were obtained with the EPhos-supported Pd catalyst P3 (4h\u20134m). A variety of functional groups could be tolerated, including a ketone (4a), a nitro group (4e), an unprotected alcohol (4i), an acetal (4l), and secondary and tertiary amines (4m, 4o, 4p, 4q). A collection of heterocycles also proved to be efficiently transformed under these conditions. Importantly, ortho-substituted substrates (4k\u20134n) reacted efficiently when P3 was employed and several densely functionalized pharmaceuticals also underwent coupling in high yields (4o\u20134q).
3-Chlorobenzonitrile did not undergo cross coupling with 1 when either BrettPhos (P1) or EPhos (P3) was employed, although a nitrile group was tolerated when a different heteroarylamine was used (4d). When using an aryl chloride bearing a methyl ester group in the ortho position, condensation took place, resulting in the formation of the tricyclic heterocycle 4j. An appreciable yield could be obtained with P3 in the presence of NaOPh (Conditions A). The unsubstituted 5H-oxazolo[2,3-b]quinazolin-5-one is previously unknown, although the thio-analog has been prepared using a copper catalyzed reaction.15
As 4-bromothiazole is also sensitive to strong base, a mild homogeneous base was similarly expected to improve reaction outcomes with this coupling partner. P3\n(A) afforded 5a and 5d in significantly higher yields with lower catalyst loadings than what has previously been reported (Scheme 1).10b Furthermore, products 5b and 5c could be obtained in excellent yields with 2.0 mol% catalyst loading at 80 \u00b0C. Although the aryl bromide was used in excess for the case of 5c, no diarylation product was observed, highlighting the high selectivity for the monoarylation product using this catalyst system. Notably, excellent yields were also obtained when aminopyrazine (5e) and aminopyrimidine (5f) were employed.
Although NaOPh is a relatively uncommon base for palladium catalyzed C\u2013N cross-coupling reactions, several previous reports have documented its use.16 Hartwig reported that KOPh was optimal for the palladium-catalyzed arylation of fluoroalkylamines, and the resting state of the catalytic reaction was determined to be a LPd(Ar)OPh complex.16a We queried whether analogous phenoxo complexes based on L1 or L3 might be observable under catalytic conditions. Subjecting a solution of L1Pd(Ar)Cl (Ar=2-MeC6H4) (OA1b) or L3Pd(Ar)Cl (Ar=2-MeC6H4) (OA3c) in THF to NaOPh at room temperature gave rise to new signals in the31P NMR spectrum 4\u20135 ppm downfield of the signals for OA1b and OA3c (see the Supporting information). The cross-coupling of aniline and 2-chlorotoluene using NaOPh as the base, and OA1b (5.0 mol%) as the catalyst was monitored by31P NMR at 60 \u00b0C in THF-d8. During the course of the reaction, these two phosphorus-containing species were predominant and were identified as the isomers of the phenoxo complex in which palladium is bound to either the 1'-aryl carbon (C-bound) or the 3-alkoxy group (O-bound) (Figure 1b).11a Interestingly, the O-bound isomer seemed to accumulate over the duration of the reaction. When the same experiment was conducted with OA3c, only the peak corresponding to the C-bound isomer was observed, suggesting that the bulky isopropoxy group disfavors the O-bound isomers.
While studying palladium-catalyzed amination reactions at room temperature, we observed a complex but reproducible kinetic profile for the cross-coupling of 3-bromoanisole and n-propylamine when using the L1-based complex LPd(II)ArBr (OA1, 0.7 mol%) as the palladium source and NaOtBu as base(Figure 4).17 In contrast, when the L3-based complex OA3 was used, a rapid reaction with a simple kinetic profile was observed. Although the complex kinetics observed with OA1 precluded a quantitative comparison of rates, the calorimetric data indicatedthat L3 was much more efficient with full consumption of starting material in less than 20 minutes (Figure 4, inset) compared to 250 minutes for L1.
In conclusion, a new ligand (L3, EPhos) for the palladium catalyzed C\u2013N cross-couplings has been developed, which was applied to the formation of 2-(hetero)arylaminooxazoles and 4-(hetero)arylaminothiazoles. Furthermore, experiments have demonstrated that the respective palladium(II) phenoxo complex is the resting state for this reaction when NaOPh is applied as the base. The O-bound isomer was not observed if L3 was used as the supporting ligand (Figure 3). Although this phenomenon does represent a significant difference in behavior between L1 and L3, ongoing studies will elucidate whether this equilibrium accounts for the difference in efficiency observed between these ligands.
", "answer": "Using mechanistic insight, a new ligand (EPhos) for the Pd-catalyzed C\\xe2\\x80\\x93N cross-coupling between primary amines and aryl halides has been developed. Employing an isopropoxy group at the C3-position favors the C-bound isomer of ligand-supported Pd(II) complexes and leads to significantly improved reactivity. The use of a catalyst system based on EPhos with NaOPh as a mild homogeneous base proved to be very effective in the formation of 4-arylaminothiazoles and highly functionalized 2-arylaminooxazoles. Previously, these were not readily accessible using Pd-catalyzed methodology.", "id": 791} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na child is brought into a pediatric emergency unit with an unprovoked , afebrile first seizure .\nwe conduct a clinical assessment of the child and rule out any acute metabolic , traumatic or infectious causes and consequently , make the diagnosis of an epileptic seizure .\nthe international league against epilepsy suggests that following such a diagnosis , the next step should be the appropriate classification of the seizure type , after which an appropriate syndrome diagnosis should be made .\nshould an electroencephalogram ( eeg ) be arranged for this child and if so , should it be arranged within 24 h or within the next week ?\nif we decide not to arrange an eeg this time and to do so if any further seizures occur , are we practicing evidence based medicine ? a recent guideline published by the royal college of pediatrics and child health ( rcpch ) asserted : there is no need for an eeg following a first simple afebrile seizure .\n this is a very bold and clear statement however , what evidence and what quality of evidence is this statement based upon ? this review analyses and discusses prominent literature regarding this widely - discussed topic .\nwhilst literature on this controversial subject matter is very diverse , a large proportion of the debate surrounds the utility of the eeg for the counselling of parents / family following a first seizure ; particularly as to whether it is a viable tool to predict seizure recurrence .\none study conducted by stroink et al . aimed to assess the accuracy of the diagnosis of a first unprovoked seizure in childhood , the recurrence rate within 2 years , the risk factors for recurrence and the long - term outcome 2 years after recurrence .\na panel of three neurologists confirmed the diagnosis of seizure in children based on pre - described diagnostic criteria .\nall the children deemed as having a seizure had a standard eeg , if it did not disclose an epileptiform abnormality , a second eeg was performed after partial sleep deprivation , or during daytime sleep .\none of the most interesting results was the recurrence rate of 71% in children who had an epileptiform eegs in standard eeg .\nthey concluded by stating that an eeg with epileptiform abnormalities proved to be the main risk factor for recurrence .\nhowever , we must consider whether having this information after the first seizure would change our practice ; it must be noted that a significant proportion ( 29% ) of children with epileptiform eegs did not have a recurrence .\nthe authors , in their prospective cohort study on 347 children with a first , unprovoked afebrile seizure showed that children with an idiopathic first seizure who had an abnormal eeg were at an increased risk of seizure recurrence .\n54% of those with epileptiform eegs experienced a second seizure , in contrast to 25% recurrences in those who exhibited a normal eeg .\nthey concluded that an abnormal eeg , particularly an epileptiform abnormality , is associated with a higher risk of seizure recurrence in children with an idiopathic first seizure . whilst shinnar et al .\n, have clearly demonstrated the higher risk of seizure recurrence in children with interictal eeg abnormalities , it is essential that we remember that a significant proportion of children with an abnormal eeg had no seizure recurrence . although , an abnormal eeg would increase the risk of recurrence by nearly two folds , whether this has to be included in counseling patients and families is debatable , as an abnormal eeg is not an absolute predictor of seizure recurrence , and a normal eeg may be falsely reassuring . a review of literature conducted by pohlmann - eden et al . on the use of the eeg and neuro - imaging following an epileptic seizure also focused on the potential interpretations and limitations of the eeg following a first seizure .\nthey reviewed literature ( children and adults ) on seizure recurrence , timing of eeg , yield of abnormalities on eeg , yield and timing of sleep deprived eeg and focal epileptiform activity in relation to recurrence .\nthey concluded that an early abnormal eeg especially , when showing focal epileptiform activity seems to be an excellent predictor for seizure recurrence .\nwould a physician be able to effectively counsel children and carers based on the percentages identified in the studies appraised above and more importantly , is having a recurrence rate for any type of seizure contributory to the management or counselling of patients ?\nanother argument put forward by advocates of the use of eeg - after first seizure is its application as a prognostic marker . dr panayiotopolous , from the department of clinical neurophysiology and epilepsy at st .\nthomass hospital , recommended that a revision of the current practice in pediatrics of not requesting an eeg after the first afebrile seizure may be needed .\nhe argued that the current practice of treating after two seizures is not in keeping with the best - available evidence .\nhe commented that an abnormal eeg , particularly generalized spike wave discharges have been reported as a consistent predictor of recurrence in nearly all studies .\nhe discussed the benefits of having an eeg after first seizure ; these include diagnosis of a specific epileptic syndrome , making a diagnosis of benign childhood partial seizures ( as these children may not have more than a single episode ) and also assessing the diagnostic and management applications of minor seizures ( such as absences and myoclonic jerks ) .\nhe clearly defined the advantages of an eeg after the first seizure , stating that the child and the family are entitled to a diagnosis , prognosis and management that is specific and precise , even though this may only be possible in a select - proportion of patients after the first seizure .\nin his recommendations , panayiotopoulos also commented that the eeg was a harmless investigation ; this point brought disagreement from pediatric neurologist , richard appleton .\nhe emphasized that although the eeg was harmless with regards to its invasiveness , it could be potentially harmful in terms of its interpretation . due to the variability in the quality of eeg reports and interpretation\n, there may be a significant number of inaccurate diagnoses , which could consequently lead to serious medical , psychological and social consequences .\nhe also added that irrespective of the eeg changes , many children would not be treated after a first seizure owing to the high non - recurrence rates after first seizures .\nhe has also pointed towards the fact that most children are managed outside tertiary epilepsy centers and may not have access to medical personnel who should be undertaking and reporting eegs .\nthe author has clearly highlighted very important issues that would be of immense practical importance and would also initiate thinking in these under - emphasized areas of this contentious topic .\nsome of the pitfalls of pediatric eeg interpretations were also discussed by tan et al .\n; their article was written in response to the clinical guidelines published by the national institute of clinical excellence ( nice ) in 2004 .\nthey stated that the eeg has rarely been able to function as a black or white or yes or no \ndiagnostic test for epilepsy , whilst also commenting that the normal eeg evolves and matures with time , reaching the normal adult pattern by approximately 12 years of age .\nthey proceeded to describe eeg reading as an inexact science , which is learnt through experience and stated that the accuracy of eeg interpretation relies heavily on the clinical history provided by the physician , which on many occasions is insufficient .\nthey discuss the fact that in the united kingdom , eegs are reported by different medical practitioners including neurophysiologists , neurologists ( both pediatric and adult ) , psychiatrists and even general practitioners with a special interest in the eeg .\nmany of these practitioners will have had very little exposure to children and pediatric epilepsy , thus , it is difficult to monitor the quality of eeg reporting .\nthe authors have clearly highlighted the varied quality of eeg reports in various settings and therefore , this has to be considered when using the eeg to guide management of an individual case , especially , if the eeg has been acquired after a first unprovoked seizure . another argument that has been put forward against the routine use of the eeg following the first seizure is whether or not it will contribute to diagnosis or management .\nconducted a medline search from 1980 to 1998 to quantify and analyze the value of expected information from an eeg after first unprovoked seizure in childhood .\nthey employed an evidence - based analytical approach to published literature to select studies providing reasonable estimates of the value of eeg in the general population of children with first unprovoked seizure .\nnext , the information from these studies was quantified using linear information theory and their results showed that the likelihood of making a clinically useful diagnosis by performing an eeg in every child after first seizure was low .\nin addition to this , they commented that as a result of the low sensitivity and specificity of the eeg , many false predictions could occur , thus , resulting in unnecessary patient distress or reassurance .\nthe quality of expected information from the eeg is too low to affect treatment recommendations in most patients , thus , they concluded by stating , eeg should be ordered selectively , not routinely , after first unprovoked seizure in childhood .\ntheir conclusion was countered by berg et al . who stated that gilbert et al .\nfocused on the impact of eeg on treatment decisions and neglected much of the additional value of an eeg .\nhe argued that an eeg following the first seizure may provide valuable diagnostic and prognostic information despite epilepsy being a clinical diagnosis .\nfurthermore , an abnormal eeg in an appropriate clinical context may help support the diagnosis of a seizure disorder , whilst also helping to distinguish between partial , and generalized seizures . in their study , gilbert and\non the utility of eeg for diagnosis following first seizure , which stated that differentiating partial from generalized seizures was non - specific ; berg et al . argued that this non - specific distinction has fundamental treatment implications if recurrent seizure occur , as the first line anti - epileptic drugs are different for partial and generalized epilepsy.[911 ] however , it is important to note that although differentiating partial and generalized epilepsy may have treatment implications ( it is not common practice to treat after first seizures ) these are not specific syndromic diagnoses and thus , having this information may not contribute to the first counseling the child or carers receive .\nboth nice and scottish intercollegiate guidelines network in their guidelines acknowledged that epilepsy is primarily a clinical diagnosis and that , in isolation , the eeg should not be used to make a diagnosis of epilepsy . at present , the majority of pediatricians do not request an eeg after a first seizure and this practice has been emphasized at a recent rcpch guideline appraisal .\neeg carried out at this point has a low sensitivity and specificity for recurrence rates , which may lead to false predictions .\ntherefore , the information on recurrence may not be helpful in counseling ; however , an abnormal eeg would increase the risk of recurrence by nearly two folds .\nthere are also a significant proportion of children with first unprovoked seizure and abnormal eeg who may not have any further seizures .\ntherefore , including the information in counseling may lead to unnecessary psychological stress for both children and carers as the finding of an abnormal eeg does not imply that the child will invariably have a further seizure .\nmost parents would opt against giving their children anti - epileptic medications after a first seizure , provided they are given the right information that it is possible that there may be no recurrence . the other aspect to consider\nis the quality of eeg interpretation that a physician receives to base his judgment on and as mentioned above , quality control of the eeg is very difficult to regulate . on the other hand , there are several clinical situations in which conducting an eeg after a single seizure can lead to the diagnosis of specific epileptic syndrome .\nsecondly , minor seizures such as absences and myoclonic jerks could be picked up , both for which prognostic and treatment implications could be deduced . children and their carers are entitled to a specific diagnosis , a prognosis , and a precise management plan .\ndiagnosis of a seizure , epilepsy type and an epileptic syndrome should be primarily based on clinical grounds .\nif it is requested , then it should be to answer a specific question , which in turn would help to aid the diagnosis of epilepsy .\nthe quality of the eeg report and its interpretation has to be considered , and if in doubt , further specialized advice should be sought . as there is limited literature on eegs after first seizure in varying age groups , conducting a prospective study to evaluate the eeg after first seizure is needed .\nin particular , to assess the influence of the eeg results on treatment decisions , social and emotional implications and seizure recurrence .\ndiagnosis of a seizure , epilepsy type and an epileptic syndrome should be primarily based on clinical grounds .\nif it is requested , then it should be to answer a specific question , which in turn would help to aid the diagnosis of epilepsy .\nthe quality of the eeg report and its interpretation has to be considered , and if in doubt , further specialized advice should be sought .\nas there is limited literature on eegs after first seizure in varying age groups , conducting a prospective study to evaluate the eeg after first seizure is needed . in particular , to assess the influence of the eeg results on treatment decisions , social and emotional implications and seizure recurrence .", "answer": "a child is brought into a paediatric emergency unit with an unprovoked , afebrile first seizure . \n we conduct a clinical assessment of the child and rule out any acute metabolic , traumatic or infectious causes and consequently , make the diagnosis of an epileptic seizure . \n the international league against epilepsy ( ilae ) suggests that following such a diagnosis , the next step should be the appropriate classification of the seizure type , after which an appropriate syndrome diagnosis should be made . \n ( 1 ) should an eeg be arranged for this child and if so , should it be arranged within 24 hours or within the next week ? if we decide not to arrange an eeg this time and to do so if any further seizures occur , are we practicing evidence based medicine ? a recent guideline published by the royal college of paediatrics and \n child health ( rcpch ) asserted : there is no need for an eeg following a first simple afebrile seizure . \n ( 2 ) this is a very bold and clear statement but what evidence and what quality of evidence is this statement based upon ? \n this review analyses and discusses prominent literature regarding this widely - discussed topic .", "id": 792} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfructose is a monosaccharide that is widely available in natural food sources such as fruits and honey .\nhowever , in most countries the main source of fructose is from sucrose , a disaccharide composed of equal portions of fructose and glucose . in the united states another major source of fructose is high - fructose corn syrup ( hfcs ) , which is a commercial liquid product consisting of fructose and glucose in varying proportions , but which in soft drinks is usually 55% fructose and 45% glucose . \nfructose intake has increased markedly over the last 2 centuries , primarily due to the increasing intake of sucrose and hfcs [ 13 ] . in particular ,\nthe introduction of hfcs in the 1970s resulted in an accelerated intake of added sugars in the usa , in part because hfcs was inexpensive and could be easily mixed in with processed foods .\nit has been suggested that the increase in added sugars worldwide may partially explain the marked increase in frequency of overweight and obese humans and may explain the rising frequency of metabolic syndrome , diabetes , hypertension , and cardiovascular diseases ( coronary artery disease , congestive heart failure , stroke , and chronic kidney disease ) [ 13 ] . \nfructose is absorbed into the intestine enterocyte by the glut-5 specific transporter . while some fructose is metabolized in the small intestinal wall , much of it\nis passed via the portal vein to the liver , with perhaps 20 to 30% escaping into the systemic circulation [ 5 , 6 ] . within the hepatocyte ,\nfructose is phosphorylated to fructose-1-phosphate by fructokinase . because this reaction has no negative feedback system ,\nthis results in the generation of amp which is metabolized by amp deaminase to inosine monophosphate and eventually to uric acid .\nthe transient atp depletion has some similarities to ischemia and can result in arrest of protein synthesis with the induction of oxidative stress and inflammation [ 79 ] . \ncirculating fructose is taken up by a variety of cell types , including endothelial cells , but also is excreted into the urine where it is absorbed via the glut-5 transporter into the s3 segment of the proximal tubule .\nthis cell also expresses fructokinase ; as such , the metabolism of fructose by this proximal tubular cell can also lead to local oxidative stress and inflammation [ 8 , 10 ] .\nfructose is known to stimulate fat accumulation in the liver by both increasing synthesis and blocking fat oxidation [ 11 , 12 ] .\nperhaps not surprisingly , clinical studies have linked the intake of excessive fructose with the development of nonalcoholic fatty liver disease in humans , and the amount of fructose ingested correlates with the risk for progression to cirrhosis [ 15 , 16 ] .\nfructose is also known to stimulate glycogen accumulation in the liver [ 17 , 18 ] , which primarily appears to be due to inhibiting glycogenolysis due to inhibition of glycogen phosphorylase .\nfructose intake has been shown to induce insulin resistance in rats [ 20 , 21 ] ; fructose can also induce insulin resistance in humans .\nthe proposed mechanisms are complex but may include a consequence of hepatic lipid deposition , with diacylglycerol accumulation leading to activation of protein kinase [ 22 , 23 ] or via the hepatic stimulation of pgc-1 . some of the effects may also be due to fructose - induced hyperuricemia with effects on endothelial and adipocyte function [ 14 , 25 ] .\nhowever , the lowering of uric acid with allopurinol did not prevent the development of insulin resistance in subjects administered large doses ( 200 g / d for two weeks ) of fructose\n. fructose intake may also accelerate the development of type 2 diabetes in rats , possibly by accelerating islet dysfunction via induction of mild islet inflammation and oxidative stress [ 12 , 27 ] .\none study suggests that this might be due in part to the effects of systemic uric acid that increase in response to fructose ( or sucrose ) ingestion .\nfructose may also stimulate the production of advanced glycation end products ( ages ) that have been shown to be toxic in diabetes .\nindeed , chronic fructose ingestion has been associated with the accelerated formation of cataracts in diabetic rats .\nintake of sugary soft drinks has also been associated with the development of obesity and diabetes . [ 30 , 31 ] indeed , a recent meta - analysis by malik et al . found a strong independent relationship between the intake of sugar - containing soft drinks with the subsequent development of diabetes .\nfructose does not acutely stimulate leptin or insulin release and hence may not trigger normal satiety responses .\nin addition , added sugars such as sucrose have been found to trigger dopamine responses in the ventral and dorsal striatum , which chronically may lead to downregulation of the d2 receptors and sugar bingeing .\nfructose intake can also induce a central leptin resistance in rats , leading to increased food intake and the development of visceral obesity .\ninterestingly , rats on a high - fructose diet may not show an increase in overall body weight unless it is associated with diets high in fat .\nfructose intake from added sugars is also associated with elevated blood pressure in humans , and diets low in added sugar have been reported to lower blood pressure .\nfurthermore , the acute ingestion of fructose ( 60 g ) can increase systolic blood pressure in humans , and this is not seen in subjects given the same dose as glucose .\nin addition , in one study , overweight men were administered 200 g fructose daily for two weeks and sustained a significant increase in ambulatory blood pressure . \ninterestingly , the increase in blood pressure in response to fructose is better observed by tail cuff measurement as opposed to intra - aortic telemetry [ 40 , 41 ] .\nhowever , blood pressure rises in response to sucrose or fructose diet by telemetry during the first hours of feeding [ 12 , 42 ] . \nthe mechanism of hypertension in response to fructose is complex but appears to be mediated by increased sodium absorption in the intestine , by inhibition of systemic endothelial function , and by stimulation of the sympathetic nervous system [ 14 , 43 , 44 ] ( figure 1 ) .\nin addition , some of the effect of fructose to increase blood pressure may be the consequence of fructose - induced increases in intracellular and serum uric acid .\nfirst , fructose - induced hypertension in rats is largely ameliorated by lowering uric acid levels .\nsecond , in one study in overweight men , the rise in ambulatory blood pressure in response to 200 g of oral fructose per day for two weeks was blocked in those subjects concomitantly administered allopurinol .\nfructose and sucrose are also known to induce renal hypertrophy and tubulointerstitial disease in rats [ 10 , 45 , 46 ] .\nfirst , the rise in uric acid in response to uric acid may cause an afferent arteriolopathy resulting in glomerular hypertension .\nsecond , fructose may also be filtered into the urine where it is taken up in the s3 segment of the proximal tubule , leading to local intracellular generation of uric acid with oxidative stress and local inflammation . \nthe administration of fructose to rats with reduced renal function ( the remnant kidney model ) can accelerate the progression of renal disease , resulting in worse proteinuria , glomerulosclerosis , and tubulointerstitial fibrosis . fructose intake also impairs calcium absorption and reduces 25-oh vitamin d and 1,25-dihydroxy vitamin d levels in this model . furthermore , the intake of sugary soft drinks in humans is associated with increased prevalence of albuminuria .\nour group has also recently administered a low - fructose diet to subjects with stable chronic kidney disease for a period of 6 weeks . while we observed no effect on renal function during the period of the study\n, we did observe a reduction in inflammatory markers and a fall in blood pressure in subjects with the dipper physiology ( i.e. , those subjects whose blood pressure spontaneously falls at night during sleep ) .\nclearly further studies are needed to determine if limiting added sugars may benefit subjects with kidney disease .\nwhile much work has focused on fructose as driving obesity , insulin resistance , and cardiorenal disease , not all fructose sources may be the same .\nthus , natural fruits also are rich in antioxidants , ascorbate , polyphenols , potassium , and fiber that may counter the effects of fructose [ 13 , 50 ] . indeed , forman et al . \nreported that fructose intake did not correlate with elevated blood pressure in a population in which much of the fructose intake was from fruit , whereas jalal et al . found a strong association of fructose intake with blood pressure when the fructose content from natural fruits was excluded . \nwhile there is increasing evidence for a role for fructose as a contributory factor to obesity and metabolic syndrome , most of the data has relied on epidemiological studies , experimental models , and cell culture .\nin contrast , studies in which fructose or sucrose is administered to subjects have shown variable effects on metabolic parameters .\nin general , few metabolic effects are observed with fructose when it is given to young , healthy , and lean subjects [ 5254 ] .\nthis contrasts with studies in overweight / obese or insulin - resistant subjects in which metabolic effects from fructose or sucrose are commonly observed [ 22 , 26 , 5558 ] .\none potential explanation may relate to the absorption of fructose , which is known to increase with fructose exposure [ 59 , 60 ] .\nfructose effects are also potentiated by glucose [ 61 , 62 ] , and most studies have only examined fructose alone .\nmost studies also show , both in animals and humans , that the effects of fructose are greater on postprandial lipids , fatty liver , and insulin resistance rather than on weight gain per se . indeed , the effects of fructose may be more on inducing leptin resistance , and it may require the addition of high - fat diet to show the weight gain .\nnevertheless , the evidence that excessive intake of fructose may have multiple adverse effects on human health seems to be mounting .\nthere are likely multiple mechanisms driving the current epidemic of obesity , diabetes , and cardiorenal disease .\nfuture studies should investigate the effect of reducing fructose intake or blocking the metabolic effects of fructose as a means for preventing or treating these important diseases .", "answer": "fructose is a sugar present in sucrose , high - fructose corn syrup , honey , and fruits . \n fructose intake has increased markedly in the last two centuries , primarily due to increased intake of added sugars . \n increasing evidence suggests that the excessive intake of fructose may induce fatty liver , insulin resistance , dyslipidemia , hypertension , and kidney disease . \n these studies suggest that excessive intake of fructose might have an etiologic role in the epidemic of obesity , diabetes , and cardiorenal disease .", "id": 793} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin response to the changing needs of the community , dental practice is subject to constant changes .\nthese changes , in turn , influence patient expectations from dentists . to successfully serve the community as a health care professional\n, dentists must be competent not only in their clinical practice , but also in some non - clinical aspects of their practice .\nprevious studies in the united states , france , the netherlands , and mexico have shown some deficiencies in non - clinical competencies including legal and financial performance , time and quality management , occupational health and practice organization among dentists and dental students . in order to improve non - clinical competencies of dentists , various approaches have been implemented such as holding educational courses for dental students , revision of dental curricula [ 810 ] and holding continuing education programs for dentists .\ndentists in iran are trained based on a national dental curriculum focusing mainly on clinical competencies , with no specific course on non - clinical domains such as professional health , communication skills , practice management or evidence - based dentistry .\nmoreover , the discipline - based nature of the curriculum acts as a barrier against integrated and comprehensive education .\nalthough the revised national curriculum debuted in 2012 attempts to cover some of the above - mentioned deficiencies , some problems still remain among the practicing dentists .\nthis calls for specific courses in the form of continuing education programs in order to make dentists competent in non - clinical domains of dental practice . in the current study\n, we designed , implemented and evaluated the efficacy of a comprehensive course on non - clinical competencies that dentists must possess for a successful dental practice .\nthis interventional study with a before - after design was performed in the school of dentistry , tehran university of medical sciences in 2010 .\nfirst , in an expert panel of five academic staff members and five general practitioners , the topics for a course on successful dental practice were derived through a nominal group technique .\nbased on the consensus of the participants , 12 topics were chosen that are not covered by the national dental curriculum either partially or completely and there was a need for complementary or continuing education courses on them .\nthe course plans for the 12 topics ( table 1 ) were designed by the expert panel members in the form of a two - day course .\nthe derived topics and the subheadings of the two - day educational course on successful dental practice for dentists in order to acquire an adequate sample , three different sampling approaches were implemented .\nfirst , a short message introducing the program was sent to 1000 randomly selected cellphone numbers of dentists practicing in tehran province .\nthird , the chief dental officers of tehran city informed the dentists working in health centers about this course .\nthey were invited to participate in the program , which was conducted in january 2010 , at the school of dentistry , tehran university of medical sciences .\nbased on the derived course topics , a questionnaire was designed to assess the participants opinion about the necessity of attending the program on each topic for dentists , their self - assessed awareness of each topic and their knowledge of the course contents .\nage , sex and work experience ( in months ) were asked as demographic information of subjects .\nsome questions regarding the quality and efficacy of the course were also included in the post - test questionnaire .\nthe participants were asked to express their level of agreement with the necessity to receive training on each topic covered in the course using a five - point likert scale from 1 meaning no necessity to 5 meaning maximum necessity .\nthe dentists were asked to report their knowledge of the course ( separately for each topic ) using a five - point likert scale from 1 meaning no knowledge to 5 meaning maximum knowledge .\nan anonymous questionnaire was administered among the participating dentists on the first day before commencement of the program as pre - test . the same questionnaire , with additional questions about the quality and efficacy of the course ,\nwas completed by the dentists at the end of the course on the second day .\neach participant assigned a three - digit code to the pre - test questionnaire to be re - entered in post - test questionnaire .\nfirst , in an expert panel of five academic staff members and five general practitioners , the topics for a course on successful dental practice were derived through a nominal group technique .\nbased on the consensus of the participants , 12 topics were chosen that are not covered by the national dental curriculum either partially or completely and there was a need for complementary or continuing education courses on them .\nthe course plans for the 12 topics ( table 1 ) were designed by the expert panel members in the form of a two - day course . the derived topics and the subheadings of the two - day educational course on successful dental practice for dentists\nfirst , a short message introducing the program was sent to 1000 randomly selected cellphone numbers of dentists practicing in tehran province .\nthird , the chief dental officers of tehran city informed the dentists working in health centers about this course .\nthe program was explained to the volunteer dentists . they were invited to participate in the program , which was conducted in january 2010 , at the school of dentistry , tehran university of medical sciences .\nbased on the derived course topics , a questionnaire was designed to assess the participants opinion about the necessity of attending the program on each topic for dentists , their self - assessed awareness of each topic and their knowledge of the course contents .\nage , sex and work experience ( in months ) were asked as demographic information of subjects .\nsome questions regarding the quality and efficacy of the course were also included in the post - test questionnaire .\nthe participants were asked to express their level of agreement with the necessity to receive training on each topic covered in the course using a five - point likert scale from 1 meaning no necessity to 5 meaning maximum necessity .\nthe dentists were asked to report their knowledge of the course ( separately for each topic ) using a five - point likert scale from 1 meaning no knowledge to 5 meaning maximum knowledge .\nan anonymous questionnaire was administered among the participating dentists on the first day before commencement of the program as pre - test . the same questionnaire , with additional questions about the quality and efficacy of the course ,\nwas completed by the dentists at the end of the course on the second day .\neach participant assigned a three - digit code to the pre - test questionnaire to be re - entered in post - test questionnaire .\nforty - six dentists with a mean age of 40.8 years ( range 25 to 58 years ) participated in this study .\nthe mean work experience of the participants was 163.3 months ( range 10 to 480 months).table 2 shows the distribution of responses regarding the necessity for training on each specified topic before and after participation in the course . as seen in table 2 , at least two - thirds of the participants in both pre- and post - tests stated that they believed training on all topics was necessary ( a score of 4 or 5 ) . in terms of necessity of receiving training on each topic before the course , the highest priority was given to ergonomics and occupational health as 93.4% of the respondents gave a score of 4 or 5 to this topic .\nthe topic with the least priority before the course was workplace design since 67.4% of the participants gave a score of 4 or 5 to this topic .\nafter the course , the most necessary topic was reported to be management of medical emergencies ( 95.6% gave a score of 4 or 5 ) , and the least necessary topic covered by the training course was documentation principles and it applications in dentistry ( 68.9% gave a score of 4 or 5 ) . before attending the course , less than 40% of the participants assessed their level of knowledge to be high ( a score of 4 or 5 ) about 10 of the 12 topics .\nhowever , this value decreased to two topics after the course ( table 3 ) .\ndistribution of the responses by a group of dentists ( n=46 * ) regarding the necessity of training on each specified topic using a five - point likert scale from 1 ( the least ) to 5 ( the most ) before and after participation in a course on successful dental practice the maximum number of unanswered questions was 2 .\ndistribution of the responses by a group of dentists ( n=46 * ) regarding the self - assessed knowledge about each specified topic using a five - point likert scale from 1 ( the least ) to 5 ( the most ) before and after participation in a course on successful dental practice the maximum unanswered questions was 2 in pre - test and 7 in post - test .\nthe opinion of the participants regarding the necessity of receiving training on two topics significantly changed after the course and they gave a higher priority to ergonomics and professional health and communication skills in post - test compared to the pre - test ( p<0.05 ) ( table 4 ) .\nthe self - assessed knowledge of the dentists improved significantly after attending the course on seven topics including the ergonomics and occupational health , workplace design , documentation principles and it application in dentistry , national rules and regulations of dental practice , medical emergencies , dental ethics and communication skills ( p<0.05 ) ( table 4 ) .\ncomparison of pre- and post - teat scores of self - perceived need for education and self - assessed knowledge about each specified topic among a group of dentists ( n=46 ) attending a course on successful dental practice wilcoxon signed - rank test regarding the quality and efficacy of the course , more than 70% of the participants were completely satisfied or satisfied with practical implication of the course , conformity of course contents with the title and course settings .\nmoreover , 87% of the participants completely agreed or agreed that more training in this field was required .\nin the present study , a course on successful dental practice was designed and its effect on self - assessed need for training and self - assessed knowledge in this regard was investigated through a before - after design .\nthe course mainly focused on non - clinical competencies that a general dentist should possess .\ndesigning a comprehensive course covering a wide range of topics related to successful dental practice , focusing on weaknesses of the national dental curriculum and implementing the views of the dentists as the main stakeholders in designing the course can be considered as the strengths of our study . on the other hand , lack of a control group ,\nshort - term evaluation and using a questionnaire for the course evaluation were weaknesses of our study .\nhowever , with regard to the fact that no similar course in iran or elsewhere was found , designing such a course per se was one of the main goals , which was achieved .\na study aiming to explore important aspects of practice and patient management among dental residents and their views on the level of undergraduate training regarding these subjects was done in the united states .\nthe results showed that the most important topics included time management , multidisciplinary coordination and total quality management .\nrespondents considered dealing with health care payers to be important to their future practices while this topic received low priority in their curriculum . another study in france on senior dental students who had the experience of working as associates in dental offices as a part of their undergraduate training showed that the two most reported problems included time management ( 90% ) and administrative matters ( 85% ) .\na study in the netherlands on newly qualified dentists showed that the most frequently reported factors responsible for being unprepared for practice were law and insurance matters ( 61.2% ) , practice organization ( 56.6% ) and staff management ( 55.2% ) . in our study , ergonomics and professional health received the highest priority in self - perceived educational needs expressed by dentists .\nthis finding confirms the studies reporting the high prevalence of musculoskeletal disorders among dentists [ 1416 ] and emphasizes on providing the dentists with sufficient training in this regard , similar to previous studies [ 17 , 18 ] .\nthe second important topic according to the dentists perspectives was management of medical emergencies in the dental office .\nthis is in line with previous studies in iran [ 1921 ] and other countries [ 2224 ] calling for more emphasis on this topic in undergraduate dental curricula and continuing education programs .\nmoreover , only 19.6% of the participants reported to have sufficient knowledge on this topic .\nmore than 80% of the dentists reported insufficient knowledge about this topic and also workplace design .\nthis shows that although the dentists rated their self - assessed knowledge as low on this topic , they gave a lower priority to further education on this topic compared to other topics .\nhowever , it should be noted that more than two - thirds of the dentists felt that there was a need for more training even on this topic . in general , these findings show the deficiency of the national dental curriculum and continuing education programs in non - clinical aspects of dental practice . in seven out of 12 topics ,\nthis increase was significant in ergonomics and professional health and communication skills , showing that the course successfully revealed the need for further education among the participants .\nthis increase was significant for seven of the 12 topics , showing that the course in general was successful in enhancing the self - assessed knowledge of the dentists in short - term .\nthe respondents also believed that the course was successful as most of them were satisfied with the course content and conduction . since no similar course has been reported in previous studies , it was impossible to compare our results with those of other studies .\nstudies on educational interventions covering some of our topics for dental students [ 6,7 , 25 ] have reported positive results in increasing the knowledge and improving the attitudes of the participants .\nin conclusion , a need for more training on non - clinical domains of dental practice was evident among the dentists .\nthe designed course seemed to be successful in revealing the participants need for further education . with regard to the satisfaction rate of the attendants", "answer": "objectives : we aimed to design , implement and evaluate the efficacy of a comprehensive course on non - clinical competencies that dentists must possess for a successful dental practice.materials and methods : in this interventional before - after study an expert panel of five academic staff members and five general practitioners derived the topics for a course on successful dental practice , and aggregated them in the form of a two - day course . \n it was held for 46 randomly selected dentists in january 2010 , at the school of dentistry , tehran university of medical sciences . \n the participants completed an anonymous questionnaire asking about their self - perceived need to receive training in each of the proposed topics and their self - assessed knowledge about each topic before and after attending the course.results:participants gave a higher priority to the necessity of training on ergonomics and professional health and communication skills in post - test compared to pre - test ( p<0.05 ) . \n the self - assessed knowledge of dentists improved significantly after attending the course in seven domains : ergonomics and occupational health , workplace design , documentation principles and it applications in dentistry , national rules and regulations of dental practice , medical emergencies , dental ethics and communication skills ( p<0.05 ) . \n more than 70% of the participants were completely satisfied or satisfied with practical implication of the course , conformity of the contents with the title and course settings.conclusion:the designed course seemed to be successful in revealing the need of participants for further education . \n considering the high satisfaction rate of the attendants , this course can serve as a model for continuing education purposes .", "id": 794} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntrigeminal neuralgia ( tn ) is a debilitating pain syndrome that is characterized by agonizing , paroxysmal , and lancinating pain .\nthe recommended first - line treatment for tn is medical therapy , but this often fails to provide pain relief .\nthus , second - line treatment modalities are given to patients whose symptoms are intractable or who can not tolerate medication .\nthese treatment modalities include invasive procedures such as microvascular decompression ( mvd ) , and ablative procedures such as gamma knife radiosurgery ( gkrs ) , percutaneous balloon microcompression , radiofrequency rhizotomy , and glycerol rhizolysis .\nrecently , gkrs has been used as a treatment modality in several centers for patients with concurrent medical illness who are poor candidates for mvd or who refuse more invasive surgery17,20 ) .\nother treatment modalities provide short - term pain relief at a rate of 80 - 90% ; gkrs also produces short - term alleviation of pain at similar rates , usually within 6 - 12 months after the operation2,3,7,9,11,15,18,23,29 - 31 ) . pain relief after mvd and radiofrequency rhizotomy for long - term periods has been well reported . in previous studies ,\npatients who underwent mvd and radiofrequency reported favorable long - term pain relief of for more than 5 years1,5,10,25,28,32 ) .\nhowever , long - term outcomes of gkrs for tn have been published in only a few reports12,22,29 ) .\nthus , we conducted the present study to analyze the long - term outcomes in a series of patients with tn who underwent single gkrs treatment and were followed up for a minimum of 60 months .\nbetween march 1995 and march 2009 , 40 patients with typical tn underwent gkrs at our clinic .\nindications for gkrs included medically intractable pain , > 65 years of age , refusal of invasive procedures , or failure of previous invasive procedures . among them , we retrospectively reviewed the medical records of patients with tn undergoing gkrs treatment that had a minimum follow - up of 60 months .\npatient demographic characteristics , clinical presentation , treatment history , and the radiosurgical modality were reviewed in 22 patients whose median follow - up was 92.2 months ( range : 60 - 144 months ) .\nall patients were treated with leksell gamma knife ( eleckta instruments , stockholm , sweden ) under local anesthesia . as a planning tool ,\nthe kula system was used until 2001 , and the leksell gamma plan system ( eleckta ab , stockholm , sweden ) has been used since 2001 .\nall patients were treated using a single isocenter through a 4-mm collimator helmet targeting the root entry zone of the trigeminal nerve ( fig .\nthe mean maximal dose to the target was 77.1 gy ( range , 65.2 - 83.6 gy ) .\nlong - term outcomes were established by face to face interview with a written questionnaire after the treatment in the outpatient clinic .\nthe questionnaire was devised based on the barrow neurological institute ( bni ) pain scale24 ) but modified at our institution to better incorporate the use of adjuvant medications .\nfacial pain outcomes were categorized into one of the following classes : grade i , no pain , no medication ; grade ii , no pain with medication ; grade iii , > 50% improved pain with medication ; grade iv , 50% improved pain with medication ; and grade v , no pain relief .\npatients with grade i - ii on the pain scale ( equivalent to bni grades i and iiia ) were considered to have a good treatment outcome .\npatients with grade iv - v on the pain scale ( equivalent to bni grades iv and v ) were considered to have a poor treatment outcome ( table 1 ) .\nstatistical verification was determined using spss statistic software , version 13.0 ( spss , inc .\nthe mean age was 61.5 years ( range 25 - 84 years ) , and the mean symptom duration from onset to treatment was 46.8 months ( range 1 - 84 months ) .\nthe most common distribution of pain involved the second and third divisions of the trigeminal nerve , observed in a total of 40.9% of patients ( 9 out of 22 patients ) .\nthirteen patients had right - sided pain , and 9 had left - sided pain . during the last follow - up period ,\n6 patients ( 27.3% ) had good treatment outcomes ( represented by grades i and ii ) , and 7 patients ( 31.8% ) had poor treatment outcomes ( represented by grades iv and v ) during a median follow - up period of 92.2 months ( range 60 - 144 months )\n. of the 6 patients with good outcomes , 4 patients ( 18.2% ) experienced complete pain relief without medication , and 2 ( 9.1% ) had complete pain relief with medications .\nof the 7 patients with poor outcomes , 5 patients ( 22.7% ) experienced 50% improved pain with medication , and 2 ( 9.1% ) had no pain relief ( table 3 ) . subgroup analysis of excellent , good , and poor outcomes found 2 statistically significant factors related to achieving and maintaining complete pain relief : symptomatic periods before treatment ( p=0.035 ) and previous surgery ( p=0.008 ) .\nhowever , sex , age , pain distribution , and laterality of pain did not correlate with facial pain improvement ( table 4 ) . out of a total of 22 patients ,\n16 patients had been treated with medication only before gkrs ( primary group ) , and 6 had gone through mvd prior to gkrs ( secondary group ) . during the final follow - up period ,\npatients with good outcomes were 37.5% and 0% in the primary and secondary group , respectively ; patients with poor outcomes , on the other hand , were 12.5% and 83.3% in the primary and secondary group , respectively ( table 5 ) .\nof the 22 patients , only one patient ( 4.54% ) experienced facial numbness after gkrs , with grade iii pain on the pain scale .\nnone of the patients had neuropathic pain , dry eye , keratitis , or jaw weakness after gkrs .\ntn patients in whom medical therapy fails are recommended to undergo several treatment modalities , including mvd , radiofrequency rhizotomy , percutaneous balloon microcompression and gkrs . in general ,\nthe most effective surgical treatment is considered to be mvd in healthy patients because it has a demonstrated effective initial pain - free rate and good long - term outcomes .\nbarker et al.1 ) reported that the pain - free rate was maintained at 70% of 1185 patients for a median of 6.2 years after mvd .\nsevere complications that developed include 2 deaths ( 0.2% ) and 16 patients ( 1% ) with ipsilateral hearing loss .\ntronnier et al.27 ) reported that 65% of patients had excellent outcomes at 10 years , and 63% at 20 years after mvd . in this study ,\nbroggi et al.4 ) reported that 53 - 94% of mvd patients were pain - free after a long - term follow - up .\nthey also reported that the mortality of mvd was 0.3% and that cranial nerve dysfunction rates ranged from 0.1 - 3% .\nadditionally , radiofrequency rhizotomy also demonstrated an effective long - term outcome for tn patients .\ntaha et al.26 ) found that 75% were pain - free at 10 years , and 23% experienced facial dysesthesia . in previous studies ,\npatients who underwent mvd reported long - term pain relief at rates of 62 - 89% , and patients who underwent radiofrequency reported long - term pain relief at rates of 20 - 82% for > 5 years after achieving a short - term pain relief rate of > 90%1,4,5,10,25 - 28,32 ) .\nhowever , severe complications have occurred in tn patients who underwent mvd or radiofrequency rhizotomy at rates of approximately 2 - 19%1,4,5,10,25 - 28,32 ) . in previous reports with long - term follow - up , gkrs for tn patients\nhas long term outcomes slightly inferior to mvd and radiofrequency rhizotomy , but with lower complication rates .\nurgosik et al.29 ) reported that 80% of 107 patients had good outcomes ( patients with 60% < residual pain ) at a median of 5 years .\nlittle et al.12 ) reported that 83% of 136 patients had good outcomes ( bni pain score of class i , ii , or iii ) at a median of 6.3 years .\nriesenburger et al.22 ) reported that 58.5% achieved good outcomes ( bni pain score of class i , ii , or iii ) at a follow - up period of 48 months .\nthese reports have demonstrated that gkrs is a safe technique for the management of tn , as trigeminal sensory disturbance , the main complication of radiosurgery for tn , only developed in approximately 10% of the patients .\nin addition , gkrs patients did not develop any of the severe complications which patients that had undergone mvd or radiofrequency rhizotomy experienced14 ) .\nhowever , most of the other reports on gkrs and tn combined the longer - term follow - up patients with more recently treated patients , thus making it more difficult to identify long - term results . in the present study ,\nwe strictly evaluated long - term outcomes at a follow - up period of a minimum of 5 years .\nthus , our data demonstrate that patients experience lasting pain relief with few complications after gkrs , although patients with good outcomes are fewer than in the previous long - term follow - up studies of outcomes after gkrs .\nthis seems to be due to the fact that only patients with no pain regardless of medication were included in the \" good outcome \" patient group in our study , whereas published reports on long - term follow - up studies on gkrs included patients with medication - controlled pain in the \" good outcome \" group .\nbecause pain negatively impacts upon the quality of life of chronic tn patients , we think that the goal of treatment in tn should be complete pain relief . therefore , we believe it is better to grade patient outcome by the reporting of pain - free outcomes that clearly separates effective pain relief from continued pain . in the current study , patients with pain that had decreased by 50% or more with the use of medication were classified separately as patients with fair outcomes . as a result\n, our data demonstrated that patients with good and fair outcomes comprise 72.7% of all treated patients , which is a similar outcome to that in previous reports .\ntherefore , from the results of this 5-year long - term follow - up study , we suggest that the proportion of patients with good outcomes , consisting purely of pain - free patients with or without medication , after gkrs was 27.3% .\npublished reports have used radiation dose protocols ranging from 70 - 100 gy7,8,21,31 ) . in general , higher doses of radiation are related to better outcomes , but complications , including facial sensory loss and paresthesia , increase at doses greater than 90 gy19,21 ) . generally , maximal radiation doses between 70 - 90 gy are used to treat tn . in previous long - term follow - up studies ,\nthe mean maximal radiation dose was approximately 80 gy , and complications included facial numbness , which affected approximately 10% of the treated patients12,22,29 ) .\nin the present study , the mean maximal dose was 77.7 gy , which is lower than that utilized in other recent studies ; this is partly due to the long follow - up period which started from 1995 , and partly because the dose was slightly lowered to avoid the development of lasting complications . in our study , only one patient ( 4.54% ) experienced facial dysesthesia . thus , we believe that lower radiation doses are associated with lower complication rates .\nthe presence of previous surgery is regarded as a predictive factor significantly associated with a poor short - term outcome6,13,16,20 ) .\nhowever , long - term pain relief factors have not been well studied until recently .\nlittle et al.12 ) recently reported that at long term follow - up , 75% of patients who were treated with primary\ngkrs achieved long - term pain relief at 7 years , but only 10% of patients in whom previous surgery had achieved a similar outcome .\nsimilarly , our study found that good outcomes in primary gkrs group ( 37.5% ) was better than in secondary gkrs group ( 0% ) , respectively .\nalso , the presence of previous surgery was observed to be a statistically significant factor related to achieving and maintaining complete pain relief according to our subgroup analysis of good and poor outcomes . based upon these findings\n, we have come to believe that there is significant correlation between previous surgery and poor long - term outcomes .\nfirst , although the pain intensity scale is validated tools for the quantification of pain , they are subjective outcome measures because they are dependent on personal interpretations and variation .\nsecond , the small sample size and retrospective study design limit the power of our outcome observations .\ngkrs performed at lower radiation doses not only decreased complication rates , but also lessened the development of more severe complications in the long run\n. however , the long - term results of gkrs for tn are not as satisfactory as those of mvd and other conventional modalities .\nalthough gkrs achieves relatively good outcomes of initial pain relief , our results suggest a steady rate of late failure , particularly among patients who performed secondary gkrs following prior surgery .\ngkrs is a safe , effective and minimally invasive treatment modality for only limited group of patients who are not suited to more invasive treatment .", "answer": "objectivegamma knife radiosurgery ( gkrs ) is the least invasive surgical option for patients with trigeminal neuralgia ( tn ) . \n however , the indications and long term outcomes of gkrs are still controversial . \n additionally , a series with uniform long - term follow - up data for all patients has been lacking . in the present study , \n the authors analyzed long - term outcomes in a series of patients with tn who underwent a single gkrs treatment followed by a minimum follow - up of 60 months.methodsfrom 1994 to 2009 , 40 consecutive patients with typical , intractable tn received gkrs . among these \n , 22 patients were followed for > 60 months . \n the mean maximum radiation dose was 77.1 gy ( 65.2 - 83.6 gy ) , and the 4 mm collimator was used to target the radiation to the root entry zone.resultsthe mean age was 61.5 years ( 25 - 84 years ) . \n the mean follow - up period was 92.2 months ( 60 - 144 months ) . according to the pain intensity scale in the last follow - up , 6 cases were grades i - \n ii ( pain - free with or without medication ; 27.3% ) and 7 cases were grade iv - v ( < 50% pain relief with medication or no pain relief ; 31.8% ) . \n there was 1 case ( facial dysesthesia ) with post - operative complications ( 4.54%).conclusionthe long - term results of gkrs for tn are not as satisfactory as those of microvascular decompression and other conventional modalities , but gkrs is a safe , effective and minimally invasive technique which might be considered a first - line therapy for a limited group of patients for whom a more invasive kind of treatment is unsuitable .", "id": 795} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese include open , laparoscopic , or endoscopic approaches . however , there are disadvantages and limitations with each of these techniques .\nthe open method requires a large incision with its associated morbidity , and the laparoscopic techniques described so far are technically challenging in the pediatric population .\nthe endoscopic approach has poor results as the cystenteric opening is small and tends to occlude leading to recurrence and infection .\nwe describe our combined technique of laparoscopic and gastroscopic transgastric cystogastrostomy for pseudopancreatic cysts in children .\nshe had high amylase and lipase levels and a computed tomographic ( ct ) scan showed necrotizing pancreatitis .\nsubsequently , an abdominal ct scan revealed a well - formed wall enhancing pseudopancreatic cyst ( fig .\naxial cut of computed tomographic scan demonstrating pseudocyst posterolateral to stomach . under anesthesia a pediatric pentax gastroscope ( pentax medical company , montvale , new jersey , united states )\nthree more 5-mm step ports were placed under direct vision : 2 ports on either side of the umbilicus and 1 port just under the costal arch to retract the gall bladder . using these ports ,\nthe stomach was insufflated with air from the gastroscope and two sutures of 30 vicryl were placed to pexy the stomach to the abdominal wall using a granee needle ( r - med , oregon , ohio , united states ) ( fig .\na 12-mm port was then directly introduced into the stomach under vision of the gastroscope as well as the laparoscope ( fig .\nit is very important to have the visualization through the gastroscope while placing the initial transgastric port as the cyst protruding from the posterior gastric wall compromises the gastric lumen severely .\nif performed without the visualization of the gastroscope there is a risk injury to the posterior gastric wall during the transgastric port placement .\none of the other ports used for gallbladder removal was then also introduced into the stomach under vision .\nthe 5-mm 30-degree telescope was then introduced into the stomach and the stomach was continuously insufflated with low flow .\na laparoscopic needle was introduced through the laparoscopy port into the cyst to confirm the position of the cyst ( fig .\na harmonic scalpel was then introduced into the stomach through the same port and an opening was made into the posterior wall of the stomach in to the cyst ( fig .\nonce this was achieved a 30-mm endo gia ( covidien , mansfield , massachusetts , united states ) stapler was introduced through the 12-mm umbilical port and a stapled cystogastrostomy was achieved ( fig .\n( a ) laparoscopic needle inserted in the posterior gastric wall to confirm the presence of pseudocyst .\n( b ) harmonic scalpel used to incise the posterior wall of stomach and the pseudocyst after needle aspiration of the pseudocyst .\n( c ) endo gia stapler being applied to the posterior gastric wall and the pseudocyst .\n( d ) endo gia stapler applied to the posterior gastric wall and the pseudocyst .\nunder anesthesia a pediatric pentax gastroscope ( pentax medical company , montvale , new jersey , united states ) was introduced into the stomach .\nthree more 5-mm step ports were placed under direct vision : 2 ports on either side of the umbilicus and 1 port just under the costal arch to retract the gall bladder . using these ports ,\nthe stomach was insufflated with air from the gastroscope and two sutures of 30 vicryl were placed to pexy the stomach to the abdominal wall using a granee needle ( r - med , oregon , ohio , united states ) ( fig .\na 12-mm port was then directly introduced into the stomach under vision of the gastroscope as well as the laparoscope ( fig .\nit is very important to have the visualization through the gastroscope while placing the initial transgastric port as the cyst protruding from the posterior gastric wall compromises the gastric lumen severely .\nif performed without the visualization of the gastroscope there is a risk injury to the posterior gastric wall during the transgastric port placement .\none of the other ports used for gallbladder removal was then also introduced into the stomach under vision .\nthe 5-mm 30-degree telescope was then introduced into the stomach and the stomach was continuously insufflated with low flow .\na laparoscopic needle was introduced through the laparoscopy port into the cyst to confirm the position of the cyst ( fig .\na harmonic scalpel was then introduced into the stomach through the same port and an opening was made into the posterior wall of the stomach in to the cyst ( fig .\nonce this was achieved a 30-mm endo gia ( covidien , mansfield , massachusetts , united states ) stapler was introduced through the 12-mm umbilical port and a stapled cystogastrostomy was achieved ( fig .\n( a ) laparoscopic needle inserted in the posterior gastric wall to confirm the presence of pseudocyst .\n( b ) harmonic scalpel used to incise the posterior wall of stomach and the pseudocyst after needle aspiration of the pseudocyst .\n( c ) endo gia stapler being applied to the posterior gastric wall and the pseudocyst .\n( d ) endo gia stapler applied to the posterior gastric wall and the pseudocyst .\nthe patient tolerated the procedure well with no intraoperative complications and was started on a regular diet on the fourth postoperative day .\nshe had well - healed scars and was tolerating a regular diet with no other problems .\npancreatic pseudocysts , because of pancreatitis , trauma , or ductal obstruction , are uncommon in children.1 however , they may require treatment if symptomatic or persist after 4 to 6 weeks\n. internal drainage of pancreatic pseudocysts has traditionally been accomplished by laparotomy , although laparoscopic and endoscopic modalities have recently been described .\nthe open technique has been shown to have mortality rates of 1 to 6% , complication rates of 10 to 40% , and recurrence rates of 5 to\n20%.2 \n the laparoscopic technique consists of either creation of an anterior gastrotomy to create a psuedocyst gastrostomy or identification of the cyst stomach interface through the lesser sac.3 both modalities have been shown to be safe and effective in the adult literature but both can be technically challenging and cumbersome in the smaller working space in children .\nendoscopic therapy alone involves identifying the region of the cyst bulge with the endoscope , needle localization of the tract , and stent placement for internal drainage .\nhowever , the cystenteric opening is limited in size which can lead to occlusion , infection , or recurrence.4 \n 5 beckingham et al performed endoscopic drainage in 34 adults with a success rate of 71% .\nthe failures were found to be associated with pseudocysts complicated by acute necrotizing pancreatitis and cyst wall thickness greater than 1 cm.6 repeated procedures due to catheter - related complications requiring additional anesthetics are not ideal in the pediatric population .\nmelman et al compared the three techniques for drainage of pancreatic pseudoscyts in adults and found lower primary success rates for endoscopic drainage as compared with laparoscopic and open cystgastrostomies as well as the need for repeat procedures.5 \n the approach of combined laparoscopic and endoscopic / gastroscopic pseudocyst gastrostomy using intraperitoneal and as well as intragastric visualization has been described in the adult literature but has not been previously reported in children.4 \n 7 the use of the laparoscopy during cystgastrostomy allows for pseudocyst debridement , fashioning a large communication between the cyst and stomach , as well as minimizes the risk of complications such as gastric perforation .\nin addition , laparoscopy adds the ability to add other procedures if needed such as cholecystectomy as was done in this case .\ngastroscopy helps in visualization of the primary transgastric port placement preventing injury to the posterior gastric wall and gastric insufflation during the procedure .\nfinally , the decreased need for additional port sites leads to an improved cosmetic result which is of particular interest in the pediatric population .\nlaparoscopic gastroscopic transgastric cystogastrostomy is a safe technique for the treatment of pancreatic pseudocysts in children .", "answer": "a 15-year - old girl presented with gallstone pancreatitis . \n subsequently , a pseudopancreatic cyst developed that was diagnosed on computed tomographic scan . \n she underwent a laparoscopic and gastroscopic transgastric cystogastrostomy . in the following report \n , we describe our novel approach and technique for the above condition .", "id": 796} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the last decade , preimplantation genetic diagnosis ( pgd ) has become an important alternative to prenatal diagnosis for couples at high risk of transmitting inherited disorders to their children .\nfluorescence in situ hybridization ( fish ) has been offered for gender selection in x - linked diseases ( 1 , 2 ) , chromosomal translocations ( 3 - 5 ) , aneuploidy , and recurrent implantation failure ( 6 , 7 ) .\nprocedures using polymerase chain reaction ( pcr ) has been applied for single gene defects including x - linked diseases ( 8 - 11 ) .\nornithine transcarbamylase ( otc ; ec 2.1.3.3 ) is placed in the mitochondrial matrix where it contributes to the detoxification of nitrogenous wastes through the urea cycle , and catalyzes the synthesis of citruline from carbamyl phosphate and ornithine .\nthe otc gene is located on the short arm of the x chromosome within band xp21.1 ( 12 ) .\nit spans 73 kb , has an open reading frame of 1,062 nucleotides , and contains 10 exons and 9 introns ( 13 , 14 ) .\notc deficiency ( mim-#311250 ) is an x - linked and co - dominant metabolic disorder with partial penetrance in females ( 15 ) .\nthe phenotype of otc deficiency is extremely heterogeneous , ranging from asymptomatic adult hemizygous males to acute neonatal hyperammonemic coma in the first week of affected male babies .\napproximately 80% of heterozygous females are asymptomatic and remaining 20% show clinical severity similar to males with partial deficiencies ( 16 , 17 ) .\nthere are more than 341 mutations known to cause otc deficiency , all of which are specific for the individual families .\nmutations have been found in all exons and introns with a relative paucity of mutations in the sequence encoding the leader peptide ( exon 1 and a part of exon 2 ) and in exon 7 ( 17 , 18 ) . to our knowledge , only two cases have been reported where specific pgd for otc deficiency were carried out using multiplex or duplex - nested pcr assay and healthy babies devoid of the otc mutation were born ( 19 , 20 ) . in this study\n, we describe the successful pregnancy and birth after pgd for otc deficiency with simultaneous analyses of fish and duplex - nested pcr in korea .\nwe have applied a duplex - nested pcr for the amplification of both the causative mutation and the y chromosome specific sry gene , and fish for aneuploidy screening of chromosome x , y and 18 .\na couple was referred to our center after therapeutic termination of the second pregnancy following prenatal diagnosis for otc deficiency . in the first pregnancy ,\na male baby was born but died at 10 days after birth due to liver dysfunction accompanying hyperammonemia .\nmolecular genetic analysis of the couple 's otc gene was performed by pcr and direct sequencing at seoul asan hospital and revealed a single base substitution ( r320x ) in the exon 9 of the female partner . in the second pregnancy , the fetus\nwas identified to be an affected boy by pcr and direct sequencing on a chorionic villus sample , and the pregnancy was therapeutically terminated . in order to avoid a pregnancy with an affected baby , the couple was counseled for pgd in cheil general hospital . in order to determine the efficiency of single cell pcr and allele drop - out ( ado ) rate , primers used for the detection of the causative mutation and y chromosome specific sry gene were tested using single lymphocytes ( table 1 ) .\novarian stimulation , in vitro fertilization , and blastomere biopsy were done as previously described ( 4 , 5 ) .\nafter the blastomere biopsy procedure , the embryos were washed several times and transferred to the g2.2 medium ( vitrolife sweden ab , kungsbacka , sweden ) .\neach blastomere was washed twice through two drops of g2.2 medium and transferred into sterile 0.2 ml pcr tubes containing 5 l of alkaline lysis buffer .\nthe nested - duplex pcr analysis was performed by previously described protocol ( 6 ) .\nmutation analysis by restriction fragment length polynorphism ( rflp ) with bcli restriction enzyme was carried out only for positively amplified pcr products of blastomeres .\nthe fish analysis for chromosome x , y and 18 was done as previously described and the manufacture 's protocol ( 4 , 5 ) .\nthe embryos with the normal genotype were selected and transferred on day 4 after fertilization .\nall 10 exons and exon - intron boundaries of the otc gene were screened by pcr followed by direct dna sequencing analysis .\nthe heterozygous otc gene with r320x nonsense mutation ( cgatga ) and wild type was detected in the exon 9 of the female partner by rflp ( fig . 1 ) and direct sequencing ( data not shown ) .\nthis r320x nonsense mutation was associated with acute neonatal hyperammonemia in their first pregnancy and reduced enzyme activity by 10 - 15% ( 21 ) .\nthe efficiency and accuracy of the duplex - nested pcr analysis were tested on single lymphocytes from the heterozygous female partner and normal male partner .\npcr on single lymphocytes resulted in 90.6% ( 58/64 ) amplification rate , whereas none of the negative controls showed a positive band .\nafter ovarian hyperstimulation , a total of 18 oocytes were retrieved and 17 oocytes were injected using intracytoplasmic sperm injection in order to prevent dna contamination from inseminated sperm . among a total of 11 embryos ,\ntwo blastomeres per embryo from 9 embryos were biopsied and simultaneously analyzed by duplex - nested pcr and fish , and one blastomere per embryo from 2 embryos by only duplex - nested pcr . as a result of duplex - nested pcr and rflp analysis with the bcli restriction enzyme ,\nten showed successful amplification for the exon 9 of the otc gene , and the amplification rate was 90.9% , almost same as that of the single lymphocyte test .\nthere were two unaffected males , five affected males , two unaffected females , and one heterozygous female ( fig . 2 and table 2 ) .\non the other hand , out of nine blastomeres analyzed by fish , only six blastomeres were identified as chromosomally normal embryos ( fig .\nhowever , among total four unaffected embryos ( embryo 1 , 2 , 3 , and 8) diagnosed by pcr , only two embryos ( embryo 3 and 8) were identified as chromosomally normal by fish .\nthe other two embryos ( embryo 1 and 2 ) were shown to have trisomy 18 and monosomy 18 , respectively . only one male embryo ( embryo 8) was transferred , and another female unaffected embryo ( embryo 3 ) was cryopreserved at blastocyst stage on day 5 after fertilization .\nthis pgd cycle resulted in a singleton pregnancy and the genotype of the fetus was confirmed to be a normal male by amniocentesis at 16 weeks of gestation .\nthe genotype of the baby for the exon 9 of otc gene and level of ammonia were confirmed as normal .\nmost pgd cycles for x - linked disorders such as duchenne muscular dystrophy and fragile x syndrome involved the selection of female embryos which were diagnosed as normal or heterozygous . these gender selections were supported by couples at risk of x - linked recessive conditions .\nado for affected allele could lead to yielding an affected heterozygous baby , even if the female embryo was diagnosed as normal by pgd for otc deficiency .\ngender selection with fish for y chromosome - specific loci is more reliable because amplification failure could occasionally occur in single cell pcr .\nthus , our protocol with pcr and fish in this study provides higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for x - linked co - dominant defects .\nwe applied duplex - nested pcr and fish analysis in two blastomeres from each embryo , which were more than 6-cell stage .\nbiopsy of more than a quarter of blastomeres from each embryo could interfere with developmental potential of embryos .\nthus , single blastomere biopsy was applied to less than 6-cell stage embryos in this study .\nsequential pcr and fish analysis in one blastomere ( cell recycling ) was reported and could be used to detect the aneuploidy , but the rate of ado after pcr seems to be higher using this method ( 22 , 23 ) .\na duplex - nested pcr analysis was developed for the simultaneous diagnosis of a r320x mutation and a gender selection , and fish analysis was used to detect aneuploidy for chromosome x , y and 18 . as a result of duplex nested pcr and fish analysis ,\nconcordant results have been obtained from two blastomeres at the sex locus , and the amplification efficiency was 100% ( 9/9 except two blastomeres , that were not analyzed by fish analysis ) for sry .\nand the amplification rate was 90.9% ( 10/11 ) for exon 9 of the otc gene .\nseveral strategies have been developed to decrease amplification failure and ado in single cell analysis of pgd .\nthese included the development of sequential first and second polar body analysis ( 24 ) , improvement of the pcr condition by increasing the denaturation temperature and time ( 19 ) , using a more powerful lysis method ( 25 - 28 ) and the use of fluorescent pcr for mutations or linked markers and multiplex pcr ( 29 - 32 ) .\nas mentioned above , we have also endeavored to optimize single cell pcr conditions , which included longer initial denaturation time , higher denaturation temperature , and the selection of taq polymerase , the concentration of mgcl2 , and lysis methods .\nthe incidence of ado was 5 - 15% in many pgd laboratories ( 27 , 28 ) . at a preliminary experiment on single lymphocytes in this study ,\nthe ado rate for exon 9 of the otc gene was about 13.0% when using duplex - nested pcr .\nwe could not absolutely exclude the possibility of ado in the diagnosis of unaffected female embryo owing to the relatively higher ado .\nthus , fish was simultaneously applied for the aneuploidy screening and sex selection to prevent the pregnancy of heterozygous female . in this study\n, we report the successful pgd and delivery of a healthy boy in a couple at risk of transmitting the otc deficiency .\nthis was carried out by the simultaneous analysis of the duplex - nested pcr for a r320x mutation in the otc gene underlying the otc deficiency and y chromosome - specific loci , and fish for aneuploidy screening of chromosome x , y and 18 .\nthis strategy could provide higher accuracy for the selection of genetically and chromosomally normal embryos in pgd for single gene defects .", "answer": "ornithine transcarbamylase ( otc ) deficiency is an x - linked co - dominant disorder . \n a couple , with a previous history of a neonatal death and a therapeutical termination due to otc deficiency , was referred to our center for preimplantation genetic diagnosis ( pgd ) . \n the female partner has a nonsense mutation in the exon 9 of the otc gene ( r320x ) . \n we carried out nested polymerase chain reaction ( pcr ) for r320x mutation and fluorescence in situ hybridization ( fish ) for aneuploidy screening . among a total of 11 embryos , two blastomeres per embryo from 9 embryos were biopsied and analyzed by duplex - nested pcr and fish , and one blastomere per embryo from 2 embryos by only duplex - nested pcr . as a result of pcr and restriction fragment length polymorphism analysis , four embryos were diagnosed as unaffected embryos having the normal otc gene . among these embryos , only one embryo was confirmed as euploidy for chromosome x , y and 18 by fish analysis . a single normal embryo was transferred to the mother , yielding an unaffected pregnancy and birth of a healthy boy . \n based on our results , pcr for mutation loci and fish for aneuploidy screening with two blastomeres from an embryo could provide higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for single gene defects .", "id": 797} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbridging integrator-1 breast cancer 1 and 2 cyclin - dependent kinase cyclin - dependent kinase inhibitor human homolog of double minute 2 poly(adp - ribosyl)ation poly(adpribose ) polymerase 1 retinoblastoma 1 protein\nthe discovery of gleevec ( sti-571 ) , a tyrosine kinase inhibitor , was a milestone achievement in clinical oncology and this inhibitor has demonstrated remarkable efficacy in philadelphia chromosome - positive ( ph ) chronic myeloid leukemia . since then , mechanism - based approaches have been used to specifically target various kinases and/or downstream oncogenic pathways that are critically involved in cell cycle progression and tumorigenesis . however , in addition to this approach , a more recent and novel use of small - molecule inhibitors has emerged as a promising endeavor in the field of cancer chemotherapy . here , we briefly review the mechanistic basis of restoration of a tumor suppressor and its potential complications for cancer therapy .\nthe tumor suppressor function mediated by the retinoblastoma 1 protein ( rb1 ) is principally attributed to its interaction with the e2f transcription factor 1 ( e2f1 ) .\nthe rb1/e2f1 complex represses a number of e2f1-dependent transcriptional target genes that are required for the transition from g1 to s phase in the cell cycle .\nbecause rb1 is inactivated by phosphorylation mediated by the g1 cyclin - dependent kinases 4 and 6 ( cdk4 and cdk6 ) , restoring rb1 function by inactivating cdk4/6 is theoretically an obvious approach .\nalthough structural similarities among a number of cdk family members hampered the development of a cdk4/6-specific inhibitor for many years , some agents , including palbociclib ( pd-0332991 ) , have recently demonstrated promising results in phase i / ii clinical trials for human malignancies , including breast cancer . above and beyond rb1 , another tumor suppressor that is critical for numerous growth inhibitory pathways\nthe abundance of wild - type p53 protein is massively reduced as a result of ubiquitin - dependent and human homolog of double minute 2 ( hdm2)-mediated degradation of p53 .\ntherefore , dissociation of p53 from the p53/hdm2 complex is a reasonable strategy for rescuing p53 function .\nbased on the crystallographic structure of the p53/hdm2 peptide complex , small p53 peptides that mimic the region of p53 sufficient for hdm2 binding and small - molecule hdm2 antagonists have been shown to disrupt the p53/hdm2 interaction in vitro and in vivo .\nsome of these , including mi-219 , nutlin-3 , and rg7112 , have been found to be effective preclinically and have consequently moved into phase i / ii clinical trials although proteasome inhibitors such as bortezomib ( ps-341 ) may not be as specific for stabilizing p53 as these hdm2 inhibitors , other growth - inhibitory gene products , including the cyclin - dependent kinase inhibitor 1b ( cdkn1b or p27 , kip1 ) protein , can also be degraded in an ubiquitin - dependent manner .\ntherefore , it may be advantageous to re - establish a broad spectrum of growth - inhibitory functions by blocking the proteasome pathway .\nalthough the approach of re - establishing tumor suppressor function in tumors as a therapeutic option is mechanistically intriguing , there are potential dilemmas associated with the systemic restoration of tumor suppressor function .\ntumor suppressor genes are frequently mutated or deleted in cancer patients , and given that some of the mutant genes acquire oncogenic potential , this approach may simply reboot a mutant ( i.e. , oncogenic ) tumor suppressor .\neven if a tumor suppressor gene is intact , its function should not depend on other cancer - susceptible proteins .\nfor example , the cyclin - dependent kinase inhibitor 2a ( cdkn2a ) gene is not frequently deleted in cancer cells , but is inactivated by dna methylation . however , epigenetic reactivation of the cdkn2a gene may not be an effective approach if rb1 and/or p53 are deficient , because the tumor suppressor functions of the products of the 2 alternative reading frames of cdkn2a p16 and p14 proteins largely depend on rb1 and p53 , respectively .\ntherefore , for the tumor suppression approach to be fully effective , it will be important to identify a non - mutated ( or non - deleted ) tumor suppressor whose function does not rely on other tumor suppressors that might be already mutated or deleted .\nbridging integrator-1 ( bin1 ) was originally identified as a c - myc oncoprotein - interacting tumor suppressor . the bin1 gene itself is rarely mutated or deleted , but is frequently silenced in human cancer cells\nmoreover , bin1 acts as a tumor suppressor in vitro and in vivo in the absence of rb1 and p53 .\nwe recently demonstrated that bin1 , whose gene promoter is activated by e2f1 , directly interacts with e2f1 and represses its transcription , implying that a negative - feedback loop regulates bin1 gene expression .\ninterestingly , we found that e2f1 is poly(adp - ribosyl)ated by poly(adp - ribose ) polymerase 1 ( parp1 ) and that parp1 inhibition unlocks the e2f1bin1 negative - feedback loop to vigorously activate the bin1 gene , which induces g2/m arrest in the cell cycle and/or apoptosis .\nsynthetic lethality, parp inhibitors have been actively used for clinical trials in breast cancer 1 and 2 ( brca1/2)-deficient breast and ovarian cancers . however , it was unclear why parp inhibitors alone also show therapeutic efficacy , even in cancer cells expressing wild - type brca1/2 . based on our recent data ,\nthe restoration of bin1 by parp inhibitors may offer a mechanistic rationale for expanding the clinical usage of parp inhibitors over a wider range of tumor types , regardless of the status of rb1 , tp53 , and brca1/2 genes ( fig .\n1 ) . \n figure 1.small-molecule inhibitors used in cancer therapy restore the functions of various tumor suppressors in malignant cells .\nthe tumor suppressor functions of retinoblastoma 1 protein ( rb1 ) , tumor protein p53 ( tp53 , known as p53 ) , and bridging integrator-1 ( bin1 ) can be pharmacologically restored by small - molecule inhibitors , such as palbociclib ( pd-0332991 ) , mi-219 , and olaparib , respectively . in the case of p53 restoration , a human homolog of double minute 2 ( hdm2 ) , named hdm4 ( also known as hdmx ) , might interfere with the effectiveness of hdm2 antagonists , probably because of overlapping functions between hdmx and hdm2 .\np , phosphorylation ; par , poly(adp - ribosyl)ation ; dp1 ( or tfdp1 ) , transcription factor dp1 ; e2f1 , e2f transcription factor 1 ; cdk4/6 , cyclin - dependent kinase 4 and 6 ; g1/s : transition between g1 ( growth1/gap1 ) phase to s ( dna synthesis ) phase in the cell cycle ; g2/m , transition between g2 ( growth2/gap2 ) phase to m ( mitosis ) phase in the cell cycle . \n \nsmall - molecule inhibitors used in cancer therapy restore the functions of various tumor suppressors in malignant cells .\nthe tumor suppressor functions of retinoblastoma 1 protein ( rb1 ) , tumor protein p53 ( tp53 , known as p53 ) , and bridging integrator-1 ( bin1 ) can be pharmacologically restored by small - molecule inhibitors , such as palbociclib ( pd-0332991 ) , mi-219 , and olaparib , respectively . in the case of p53 restoration , a human homolog of double minute 2 ( hdm2 ) , named hdm4 ( also known as hdmx ) ,\nmight interfere with the effectiveness of hdm2 antagonists , probably because of overlapping functions between hdmx and hdm2 .\np , phosphorylation ; par , poly(adp - ribosyl)ation ; dp1 ( or tfdp1 ) , transcription factor dp1 ; e2f1 , e2f transcription factor 1 ; cdk4/6 , cyclin - dependent kinase 4 and 6 ; g1/s : transition between g1 ( growth1/gap1 ) phase to s ( dna synthesis ) phase in the cell cycle ; g2/m , transition between g2 ( growth2/gap2 ) phase to m ( mitosis ) phase in the cell cycle .\nchemotherapy and radiotherapy are conventional treatments for eradicating tumors , but cancer often develops therapeutic resistance over time . given that many tumor suppressors are proapoptotic in response to dna damaging agents , it would be clinically pertinent to increase the chemo- and radiosensitivities of cancer by combining standard treatments with agents that can restore the activity of silenced tumor suppressors , provided they are not mutated or deleted , in human malignancies .\nthis work was partially supported by a grant from the us national institutes of health ( nih ) ( r01ca140379 ) ( to d.s . ) .", "answer": "over the last decades , accumulating data have advanced our understanding of the mechanism of action of tumor suppressor proteins and therapeutic strategies to restore tumor suppressor pathways have emerged as a promising approach for cancer therapy . based on our recent findings on bridging integrator-1 ( bin1 ) , \n we outline potential advantages and disadvantages of chemical activation of tumor suppressors .", "id": 798} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nx - linked dominant chondrodysplasia punctata ( cdpx2 , omim 302960 ) is an inheritable systemic disease and is characterized by skeletal , ophthalmologic , and cutaneous manifestations . in the late seventies , rudolph happle reported a female and brilliantly recognized a group of published patients with chondrodysplasia punctata whose mosaic phenotype and sex rate corresponded with an x - linked dominant pattern of inheritance . in 1999 , the gene emopamil binding protein ( ebp ) was identified and associated with cdpx2 , so called conradi - hnermann - happle syndrome .\nthe ebp gene is located on the short arm of the x chromosome ( xp11.22-p11.23 ) and spans 7 kb of genomic dna , containing five exons coding a mature transcript of 1 kb which is ubiquitously expressed .\nthis protein consists of 230 amino acids and four transmembrane domains , it has a molecular weight of 27 kda and it is implicated in cholesterol biosynthesis .\ncutaneous lesions in cdpx2 usually start as erythematous scaly plaques following the lines of blaschko that fade over time , and some patients may be born with congenital erythroderma .\nwhile cdpx2 may exhibit variable phenotypes , psoriasiform skin lesions are exceptional and histopathologic investigations of psoriasiform skin lesions show epidermal hyperproliferation in addition to ichthyotic retention hyperkeratosis . in this report , a case of a 12-year - old girl diagnosed with x - linked dominant chondrodysplasia punctata with a psoriasiform phenotype is reported with genetical confirmation .\nwe discuss here a rare clinical presentation which helps in better depict this rare genodermatosis and on the lack of correlation between phenotype and genotype in this disease .\na 12-year - old girl , who had been born with congenital erythroderma , had a 4-month history of linear and whorled inflammatory cutaneous lesions on her trunk , leg , and arms .\nextensively distributed thickly adherent scaling had been developed at the age of one , and continued since then .\nthe patient had been born at term following a normal pregnancy and delivery and family history was unremarkable .\nshe displayed growth retardation , bilateral conductive hearing , and unilateral congenital cataract in her right eye .\nshe exhibited short stature with asymmetric shortening of her limbs , being her right arm shorter than her left .\ndysmorphic facial features with frontal bossing , flat nasal bridge , and a depressed tip of the nose were observed .\ndermatological examination revealed brown streaky hyperkeratotic plaques with thickly adherent scaling located along blaschko 's lines .\nalso , erythematous scaling and guttate lesions were observed on her trunk , arms , and legs .\nthere were patchy areas of scarring alopecia on frontal and temporal regions of the scalp and lateral regions of eyebrows .\ndorsal and lumbosacral magnetic resonance imaging showed scoliosis deformity , height losses of the t8 vertebrae left half and l3 , l4 vertebral the right halves ( tethered cord ) .\nclinical features of the patient with conradi hnermann happle syndrome ( x - linked dominant chondrodysplasia punctata ) genomic dna of the patient was extracted from peripheral blood leukocytes via a conventional phenol - chloroform method .\nexons 1 - 5 and the intronic splicing regions from the ebp gene were amplified by polymerase chain reaction ( pcr ) as previously described .\nthe reaction was conducted in a 2720 thermal cycler ( applied biosystems , foster city , ca , u.s.a . ) .\nautomatic sequencing was performed with the abi prism 310 genetic analyzer ( applied biosystems ) .\nwe identified a previously reported ebp mutation , c. 440 g > a ( p.r147h ) in the patient , but not in her parents [ figure 2 ] . according to the clinical and laboratory findings\n, the diagnosis of conradi - hnermann - happle syndrome was established . a skin biopsy of one of the guttate , erythematous , and scaling plaques revealed retention hyperkeratosis , parakeratosis , acanthosis with regular elongation of rete ridges , capillary proliferation , and mononuclear cell infiltration in papillary dermis , being this consistent with a psoriasiform pattern .\nthe pedigree and dna sequencing showed a heterozygous mutation c. 440 g > a resulting in p.r147h in ebp gene\nin conradi - hnermann - happle syndrome , cutaneous findings are remarkable and characterized by hyperkeratotic lesions on an erythematous background following the blaschko 's lines .\nbruch et al . described a unique adult patient presenting both with ichthyotic and pustular psoriasiform lesions together .\nlater , in a large spanish series , a patient with ichthyosis in a psoriasiform pattern was reported with the genetic analysis showed c. 187c > t ( p.arg63x ) de novo mutation .\nwe here present an exceptional case of cdpx2 with psoriasiform and ichthyotic skin lesions together in an adolescent , the first case from tunisia .\nhistopathological features of guttate , erythematous , and scaling plaques followed a psoriasiform pattern . in 1999 , the gene ebp was identified and associated with the conradi - hnermann - happle syndrome ( xp11.22-p11.23 ) . to date , about 70 different mutations in the ebp gene have been described related with this disease .\nwe found a c.(440 g > a ) missense de novo mutation in the ebp gene ( p.arg147his ) , placed in the second endoplasmic reticulum domain ( er2 ) of the protein .\nthe unique case of cdpx2 with a similar phenotype to ours displayed a c.(187c > t ) , p.arg63x nonsense mutation , which had also been described in two patients with typical skin phenotype of cdpx2 .\nthe c. 440 g seems to be a nucleotide with particularly high mutational susceptibility within the ebp gene , a hot spot .\non the other hand , the clinical phenotype associated with this mutation has been variable , which subscribes the lack of correlation between genotype and phenotype in this disease .\nalthough the relationship between the various genotypes and phenotypes in conradi - hnermann - happle syndrome has not been fully elucidated , detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling .\nour case expands the clinical phenotypic variation in cdpx2 and further demonstrates the lack of correlation between genotype and phenotype in this disease .\nunique additional clinical manifestations like plaque - type psoriasis may present with different mutations . conradi - hunermann - happle may represent extensive plaque - type psoriasis in adolescent patients .", "answer": "conradi - hnermann - happle syndrome ( cdpx2 , omim 302960 ) is an inherited x - linked dominant variant of chondrodysplasia punctata which primarily affects the skin , bones , and eyes . \n cdpx2 patients display skin defects , including ichthyotic lesions , follicular atrophoderma , cicatricial alopecia , and less frequently ichthyosiform erythroderma , cataracts , and skeletal abnormalities consisting of short stature , asymmetric shortening of the limbs , epiphyseal stippling , and craniofacial defects . \n cdpx2 results from mutations in emopamil binding protein ( ebp ) gene . \n the aim of our study is to identify ebp mutation in a unique case of conradi - hnermann - happle syndrome with rare psoriasiform lesions .", "id": 799} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlaparoscopic surgery has enjoyed increasing success since its modest beginning in 1983 and has become the standard of care for cholecystectomy .\nevaluation and application of new technologies has allowed for the rapid advancement of laparoscopic surgical techniques .\nwhat remains ill - defined is the application and safety of laparoscopic surgery to complex solid - organ procedures such as liver resection .\nthe difficulties in approaching laparoscopic liver surgery require continued improvements in technology , such as video imaging , electrosurgical instruments , laparoscopic duplex ultrasound , and greater success with bloodless surgery .\none possible application of advancements in laparoscopic liver surgery is the performance of partial nonanatomic hepatectomy . using open surgical techniques ,\npartial nonanatomic hepatectomy has gained acceptance as a procedure that may be used to treat patients with hepatocellular carcinoma , as well as other diagnoses .\nnonanatomic liver resection is technically demanding due to hepatic anatomic variability and can be associated with considerable morbidity .\nthis study evaluated a new technique for liver resection using the ligasure electrosurgical vessel - sealing device ( valleylab - tyco healthcare , boulder , co ) .\nit does so by combining energy control with physical compression , including a brief cool down that produces a distinctive , translucent seal of partially denatured protein ; thereby , fusing the collagen in the vessel walls and occluding the lumen entirely .\nthese seals have bursting strengths comparable to those of ligatures and , unlike clips , resist dislodgment because they are intrinsic to the vessel wall structure .\nthermal spread is minimal and the autologous seals formed by the ligasure device can withstand 3x systolic pressure . the ligasure device may be used for sealing vessels up to 7 mm in diameter .\nthe effectiveness of this device for liver resection is not known , but we hypothesize that it has excellent potential for use in laparoscopic nonanatomic liver resection .\nthis series is our initial experience with the ligasure device in the performance of laparoscopic nonanatomic resections of the liver using a sus scrofa pig model .\nthe animal experiments were performed in accordance with the 1996 national research council guide for the care and use of laboratory animals and applicable federal regulations .\npreoperatively , the animals were fasted 12 hours and medicated with hydromorphone ( 0.1 mg/ kg ) , acepromazine ( 0.1 mg / kg ) , and glycopyrrolate ( 0.01 mg / kg intramuscularly ) .\nanesthesia was induced with tiletamine / zolazepam ( telazol ) ( 6 mg / kg intramuscularly ) .\nthe animals were then intubated and given xylazine ( 2 mg / kg intravenously ) , and anesthesia was maintained using isoflurane ( 1.53% ) .\nmonitoring of the anesthetized animals was conducted using pulse oximetry for oxygen saturation , end - tidal carbon dioxide sensors , and cardiac sensors .\nthe 9 domestic swine used in the experiments weighed 29 kg to 36 kg and were divided equally into 3 groups . in all of the experiments ,\n60% to 80% of the left lobe was removed . before concluding each operation , all groups of animals ( i , ii , and iii )\nwere visually inspected for bleeding and biliary leakage at the site of resection . in laparoscopic cases ,\npneumoperitoneum was released for 10 minutes prior to the final visual inspection . in all cases , adequate hemostasis and biliary control\npostoperative analgesia for groups i and ii consisted of morphine epidural ( 2 mg ) placed between vertebrae l6 and s1 in addition to a transdermal fentanyl patch ( 75 g ) stapled to the animals ' posterior neck .\npostoperative analgesia for group iii consisted of buprenorphine ( 0.01 mg / kg q 12 hours ) and a transdermal fentanyl patch ( 75 g ) stapled to the animals ' posterior neck .\nsurgical details of liver resections were as follows : the control animals underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline by using the finger - fracture method .\nblood vessels and bile ducts were clipped or suture ligated as appropriate and electrocautery ( bovie ) was used where indicated .\nthe animals in group ii underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline .\nthe animals in group iii underwent a laparoscopic , non - anatomic , left hepatic lobectomy with the ligasure device for dividing the liver parenchyma and sealing and dividing all blood vessels and bile ducts .\nthe pneumoperitoneum was insufflated by veress needle and maintained at a constant abdominal pressure of 12 mm hg .\nthe laparoscopic atlas version of the ligasure was used to divide the parenchyma as well as any vessels or bile ducts in continuity without isolating them first .\nthis was accomplished by opening the jaws of the device and then gently applying pressure to the parenchymal surface .\nthe device was activated by depressing a foot pedal , and increasing pressure applied to the handle , slowly approximating ( closing ) the jaws .\nthe rate of compression of the parenchyma was guided by the surgeon , who maintained a 1-mm blanched area of parenchyma around the jaws .\nwhen the jaws of the device were approximated , indicated by the handle locking , the device was recycled , \nthe excised segment of the liver was placed in an endocatch bag , morselated , and removed through one of the port - site incisions .\nanimals from all groups ( i , ii , and iii ) were assessed for biliary leakage on postoperative day 2 by cholescintigraphy .\nanimals were anesthetized with telazol ( 6 mg / kg intramuscularly ) to allow administration of the radiopharmaceutical , hepatolite ( 10 millicuries ) , given via a jelco 22 gauge needle in the animals ' left lateral ear vein .\none hour later , a hida scan was performed using the adac forte camera , allowing evaluation of hepatocellular function and patency of the hepatobiliary system by tracking the production and flow of radiolabeled bile from the liver through the bile ducts and into the intestine . following the hida scan\n, all animals underwent a midline abdominal incision for gross inspection of the cut surface of the liver and the surrounding area for any evidence of hemorrhage or biliary leakage .\nupon visual inspection , no apparent evidence was present of biliary leakage , resolving hematoma , or abscess formation .\nsamples of the cut surface were taken for histological examination , and the animals were euthanized with a barbiturate overdose ( beuthanasia , 1 ml plus 1 ml/5 kg , intravenously ) .\nthe control animals underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline by using the finger - fracture method .\nblood vessels and bile ducts were clipped or suture ligated as appropriate and electrocautery ( bovie ) was used where indicated .\nthe animals in group ii underwent a nonanatomic left hepatic lobectomy through a scalpel incision in the abdominal midline .\nthe animals in group iii underwent a laparoscopic , non - anatomic , left hepatic lobectomy with the ligasure device for dividing the liver parenchyma and sealing and dividing all blood vessels and bile ducts .\nthe pneumoperitoneum was insufflated by veress needle and maintained at a constant abdominal pressure of 12 mm hg .\nthe ligasure device was introduced through a 10-mm trocar . the laparoscopic atlas version of the ligasure was used to divide the parenchyma as well as any vessels or bile ducts in continuity without isolating them first .\nthis was accomplished by opening the jaws of the device and then gently applying pressure to the parenchymal surface .\nthe device was activated by depressing a foot pedal , and increasing pressure applied to the handle , slowly approximating ( closing ) the jaws .\nthe rate of compression of the parenchyma was guided by the surgeon , who maintained a 1-mm blanched area of parenchyma around the jaws .\nwhen the jaws of the device were approximated , indicated by the handle locking , the device was recycled , \nthe excised segment of the liver was placed in an endocatch bag , morselated , and removed through one of the port - site incisions .\nanimals from all groups ( i , ii , and iii ) were assessed for biliary leakage on postoperative day 2 by cholescintigraphy .\nanimals were anesthetized with telazol ( 6 mg / kg intramuscularly ) to allow administration of the radiopharmaceutical , hepatolite ( 10 millicuries ) , given via a jelco 22 gauge needle in the animals ' left lateral ear vein .\none hour later , a hida scan was performed using the adac forte camera , allowing evaluation of hepatocellular function and patency of the hepatobiliary system by tracking the production and flow of radiolabeled bile from the liver through the bile ducts and into the intestine . following the hida scan\n, all animals underwent a midline abdominal incision for gross inspection of the cut surface of the liver and the surrounding area for any evidence of hemorrhage or biliary leakage . upon visual inspection ,\nno apparent evidence was present of biliary leakage , resolving hematoma , or abscess formation .\nsamples of the cut surface were taken for histological examination , and the animals were euthanized with a barbiturate overdose ( beuthanasia , 1 ml plus 1 ml/5 kg , intravenously ) .\nintraoperative blood loss and operative times were significantly lower using the ligasure device and are shown in table 1 .\nopen resection animals ( groups i and ii ) were depressed postoperatively , had decreased appetite , and required analgesia . in contrast , laparoscopic animals ( group iii ) were alert , responsive , and feeding ad libitum 1 hour after recovery from anesthesia .\nhistological examination of excised liver and remaining liver at sacrifice showed secure sealing of all biliary and vascular structures in the ligasure groups .\nnot unexpectedly , thermal injury from standard electrocautery was 4 times greater than that observed in tissue examined where the ligasure device was used , as measured on histological specimens .\none animal in group i had a bile leak detected on hida scan . however , this leak was not discernible upon subsequent visual inspection and was considered clinically insignificant .\nadditionally , postoperative bleeding was absent in all animals as confirmed by gross inspection on postoperative day 2 .\nlaparoscopic surgery provides benefits to the patients , such as shorter recovery time , less pain , and more cosmetically acceptable incisions .\nhowever , solid visceral organs such as the liver pose a significant challenge to the laparoscopic surgeon because they have a soft parenchyma richly interspersed with vasculature .\nrealization of the potential advantages of laparoscopic liver resection requires the technical ability to ensure hemostasis during division of the parenchyma .\nthe effectiveness of laparoscopic instrumentation in maintaining a hemostatic , clear operative field has not been well documented to date . due to this fact ,\nthe application of laparoscopic surgery to procedures on the liver has been delayed by the lack of appropriate instrumentation , and the testing of laparoscopic surgical techniques .\ngreater acceptance of laparoscopic liver resection requires careful evaluation of the safety and efficiency of available technology and techniques . to date\n, laparoscopic liver resection has been evaluated in several case studies demonstrating the expected benefits to patients : decreased postoperative pain , reduced trauma to the abdominal wall , smaller incisions , shorter hospital stay , and earlier ambulation and return to normal activities compared with conventional liver surgery . in this study\n, we evaluated the application of vesselsealing technology to liver resection in both open and laparoscopic approaches .\nour findings demonstrate effective sealing of intrahepatic blood vessels and bile ducts without requiring isolation .\nlittle to no blood loss occurred using the ligasure device as compared with that with the standard finger - fracture method of partial hepatectomy .\nour specimens did not contain any veins greater than 7 mm , and we believe that other methods , such as endovascular staplers , would be required for larger portal or hepatic vein branches .\na significant limitation of laparoscopic surgery , which has prevented application to liver resection , is the difficulty in controlling blood vessels .\nlaparoscopic suturing is difficult in the best circumstances ; trying to control a bleeding hepatic vein using laparoscopic suturing would be a formidable undertaking .\nthe ability of the ligasure device to effectively seal intraparenchymal blood vessels is a significant advancement that increases the feasibility of laparoscopic liver resection .\nthe additional finding that bile ducts were effectively sealed further strengthens the applicability of the device to liver resection .\nthe effectiveness of the ligasure in nonanatomic liver resection in this study emphasizes the importance of new surgical technology in extending the range of laparoscopic procedures available to the surgeon .\nthere is no question that liver resection , especially nonanatomic , is a technically challenging operation .\nthe application of laparoscopic techniques to these procedures should be considered only where full support for advanced laparoscopic procedures is available , and by surgical teams experienced in all aspects of liver surgery .", "answer": "background : advancements in technology have allowed laparoscopic surgery to expand into advanced procedures such as liver resection ; however , the value and safety of laparoscopic liver surgery is still a topic for debate . \n this study was designed to evaluate the feasibility and outcome of laparoscopic nonanatomic hepatectomy using the ligasure device in a swine model.methods:nonanatomic hepatic lobe resection was performed in 3 groups comparing the open finger - fracture method , the open method with the ligasure device , and the laparoscopic method with the ligasure device . \n the cut surfaces of the liver were evaluated for bleeding and biliary leakage at the time of the operation . \n the animals were inspected 48 hours later for hemorrhage and evaluated with cholescintigraphy ( hepatobiliary iminodiacetic acid [ hida ] scan ) for biliary leakage , in addition to histo - logical evaluation of liver specimens.results:no hemorrhage or biliary leakage was noted in the groups where the ligasure device was used , whereas 1 animal from the open finger - fracture method sustained a bile leak observed on hida scan . \n the operative blood loss was considerably less in the groups where the liga - sure device was used , and the shortest operative time was observed in the laparoscopic group.conclusions:the ligasure device can be safely and effectively used to perform a laparoscopic nonanatomic hepatectomy .", "id": 800} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntraumatic arterial occlusion following major or minor blunt trauma , especially in the absence of any other bony injury , is a rare phenomenon . \nmotor - scooter handlebar syndrome is one such type of arterial occlusion affecting vascular structures following direct blow by a handlebar of a motorbike or bicycle to the groin .\ngiven their superficial course at this location , femoral vessels are the most common vascular structures affected . in all instances ,\ninjury to iliac vessels remains exceedingly rare , given its posterior position within the pelvis , representing only 0.4% of vascular injuries . in this case , we highlight a delayed presentation of external iliac artery occlusion secondary to motor - scooter handlebar syndrome , in a paediatric patient .\npathophysiology and management of vascular injuries in the paediatric population vary significantly compared with the adult population .\nadditional factors which need to be considered include : smaller vessel size or vessel spasm , higher risk of infection , tendency for re - stenosis and continuing growth .\nwe review previous paediatric cases of this unusual vascular injury to highlight the pathology and most appropriate management option .\na 15-year - old male presented to the emergency department following a direct blow from his bicycle handlebars to his groin .\nhis abdominal examination was unremarkable , except for a small abrasion and visible mass in his right groin .\nafter exclusion of other abdominal or chest injuries , he was discharged on the same day with a diagnosis of right groin haematoma and follow - up in 68 weeks .\nhis symptoms included pain and paraesthesia in his right buttocks on mobilization > 100 m. he was found to have absent peripheral pulses in his right leg , although it appeared well perfused with a normal capillary refill .\nan arterial doppler ultrasound showed a right external iliac artery thrombus occluding the proximal two - thirds of the vessel .\na computed tomography scan of the abdomen and pelvis with intravenous contrast identified complete occlusion of the right external iliac artery 1 cm beyond its origin . however , the common femoral artery and profunda femoris remained patent via collaterals ( fig . 1 ) . \n\nhe underwent a right external iliac thromboendarterectomy with patch repair using a saphenous vein graft .\na suprainguinal incision was initially made in attempt to expose the proximal external iliac artery .\ndue to its extent , retrieval of the entire thrombus was incomplete and a second groin incision near the junction of the common femoral with external iliac ( at the inguinal ligament level ) was required .\nthe patient subsequently underwent a proximal and distal thrombectomy , and the arteriotomy was extended between the two incisions identifying an intimal stricture with significant fibrosis ( fig . 2 ) .\nan intimal flap was identified in the distal region and tacked down with a 7 - 0 prolene suture .\nthe long saphenous vein was harvested and the defect closed with patch repair extending from proximal iliac to proximal femoral vessel .\nat the initial 2-week follow - up , the vessels remained patent and patient was progressing well .\nsubsequently , regular biannual follow - up was planned to monitor for any longer - term complications . \n\nfigure 2:occlusion of right external iliac artery 1 cm below its origin ( white arrow ) .\nocclusion of right external iliac artery 1 cm below its origin ( white arrow ) .\n motor - scooter handlebar syndrome is an uncommon form of arterial blunt injury following a direct blow by the handlebar of motorbikes or bicycles .\nonly a handful of paediatric cases have been reported [ 1 , 2 , 47 ] . the common femoral vessel is the most commonly affected vascular structure .\na common site for these injuries is at the inguinal ligament , where the femoral artery is superficial and courses anterior to the superior pubic ramus and femoral head . as such , it is prone to compression between the handlebar and posterior osseous structures .\nin addition , it is a relatively immobile structure , tethered by arterial branches , periadventitial connective tissue and the femoral sheath .\nthey proposed that a circumferential tear of the intima leads to dissection and prolapse of the inner aortic layers , causing complete luminal occlusion .\n, patients may remain asymptomatic until a period of growth spurt or they resume more rigorous physical activity .\nthis can lead to delay in the diagnosis , and a high index of suspicion needs to be maintained to avoid ischaemic complications such as limb length discrepancy [ 8 , 9 ] .\nin such instances , it is important to rule out any secondary occlusion of the femoral artery and vein that may predispose to the development of thrombosis within these vessels .\nduplex sonography should be carried out to assess flow velocities and waveform characteristics in these patients , and is especially suited to the paediatric population as they have reduced abdominal fat , and there is no radiation .\nidentified ultrasound , in the right hands , to be highly sensitive ( 100% ) and specific ( 97.5% ) for the detection of arterial injuries when compared with surgical findings .\nopen arterial thromboendarterectomy with graft or patch repair is the standard of care for such cases in trauma centres .\npreviously documented cases include patch repair or bypass using saphenous vein , bovine pericardium and synthetic material [ 13 , 5 , 6 ] .\none case was successfully treated with iv heparinzation alone . however , in most injuries , the presence of significant groin haematoma may limit anticoagulation , requiring more urgent operative re - vascularization . in our patient , delayed presentation and presence of significant collaterals meant definitive operative management could be planned as a semi - elective procedure .\nthe role of endovascular intervention in this paediatric population has previously been documented mainly as a temporizing measure for revascularization [ 4 , 5 ] .\nused a nitinol stent in the distal superficial femoral artery of a 13-year - old patient whose arterial and venous calibre at the time of injury were of inappropriate size for reconstruction .\nthe main disadvantage of endovascular interventions in paediatric patients is the constantly enlarging calibre of the vessel with a fixed stent diameter .\nthis can predispose to complications such as restenosis , stent fracture , stent dislocation and acute on chronic ischaemia . as a result , future vascular reconstruction may be compromised and in extreme cases , this may progress to significant ischaemia and even limb loss .\nwe provide an unusual cause of external iliac occlusion secondary to bicycle handlebar injury to the groin .\nall patients presenting with groin injury from this mechanism should be carefully investigated with duplex sonography and monitored for risk of vascular injury .\nthe presence of collaterals , particularly in the paediatric population , can lead to delay in diagnosis .\nliterature seems to advocate open primary surgery for management of these injuries ; however , endovascular and conservative medical management have also been used successfully .\nthe latter two were contraindicated in our patient and open surgery was the most appropriate option .\nlong - term follow - up , beyond the 12-month period , is needed , particularly in relation to known vascular complications including pseudoaneurysms , arteriovenous fistula formation and restenosis .", "answer": "arterial occlusion following blunt trauma is an uncommon occurrence . \n we report an unusual case of delayed external iliac artery occlusion in a young male following blunt abdominal injury . \n he was successfully treated with thromboendarterectomy and saphenous vein patch repair . \n there have only been a handful of documented cases occurring in the paediatric population . \n all patients presenting with groin injury from this mechanism should be carefully investigated and monitored for risk of vascular injury .", "id": 801} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npositron emission tomography ( pet ) is a non - invasive imaging technique used to diagnose neurological and neuropsychiatric disorders .\nthis method facilitates longitudinal studies of various animal models of alzheimer 's disease , cerebral ischemia , depression , epilepsy , parkinson 's disease , and schizophrenia .\nthis compound is a radioactive analogue of glucose and altered fdg uptake indicates metabolic changes of neuronal activity in the brain .\napplication of fdg - pet in rodents for neuroscience research may be limited by unwanted extracranial accumulation of fdg in the harderian gland . unlike humans , small laboratory rodents have harderian glands that show strong fdg uptake within the orbit near the frontal region of the brain .\nhowever , one major secretory product of the gland is porphyrin , which affects photoreception and lubrication of the eyeball .\nfdg uptake in the harderian gland varies greatly depending on study conditions prior to pet imaging such as the use of anesthesia during the uptake period .\nmoreover , other radioactive tracers like c - pib and f - fallypride reportedly accumulate in the harderian gland as well .\nthis characteristic of the harderian gland makes it difficult to obtain exact measurements of fdg uptake near the frontal brain region because it is impossible to account for the radioactive spillover coming from the adjacent harderian gland . to resolve these problems , surgical procedures for harderian adenectomy ( ha )\nsince the mouse brain is significantly smaller compared to rat brain , the additive effect of the harderian gland on fdg uptake measurement is much greater .\nthe purposes of the present study were to develop a surgical procedure for ha in mice and to assess the effectiveness of this procedure for improving fdg - pet .\nadult balb / c mice ( 22.0 1.9 g ; orientbio , korea ) were used for all experiments .\ntwo mice were used for unilateral ha , and six mice underwent bilateral ha and control operations , respectively .\nthe experimental procedure was approved by the institutional animal care and use committee of konkuk university , korea .\nha was performed in mice anesthetized intraperitoneally with zoletil ( 90 mg / kg ; virbac , france ) and xylazine ( 10 mg / kg ; bayer , germany ) .\nthe whiskers were clipped , and then the conjunctival sac and periocular skin were disinfected with povidone - iodine diluted ( 1 : 50 ) in saline .\nmice were placed in a lateral recumbent position and the nictitating membrane was pulled toward the lateral canthus using serrated micro - dissecting forceps ( fig .\nat the base of the nictitating membrane , the medially protruding , cream - colored harderian gland could be seen under the thin conjunctival tissue ( fig .\nthe conjunctival tissue that covered the gland was incised using the tip of a surgical blade .\nonce removed , the space between the eye and orbital rim was examined for residual glandular tissue . during the resection procedure ,\na small amount of bleeding occurred but stopped once slight pressure was applied with a cotton swab .\npostoperative care was immediately provided and performed once a day for the next 3 days .\nophthalmic antibiotic ointment ( terramycin ; pfizer , usa ) and solcoseryl eye gel ( solcorin ; hanlim pharm , korea ) were applied for protection against infection and to lubricate the eyes .\nan analgesic ( ketoprofen , 5 mg / kg ; unibiotech , korea ) was also administered subcutaneously daily for 3 days .\nthe adenectomized mice were subjected to fdg - pet scans on postoperative days 5 , 10 , 15 , and 30 .\nfdg ( 300 ci ; korea institute of radiological and medical sciences , korea ) was injected via the lateral tail vein while the mice were anesthetized with 2% isoflurane ( jw pharmaceutical , korea ) .\nthe mice were positioned on the scanning bed , and pet was performed for 20 min in an inveon pet / ct system ( siemens healthcare , usa ) .\nthe acquired pet emission data were reconstructed using a fourier re - binning algorithm with three span and 31 ring difference , and ordered subsets expectation maximization 2d algorithm with 16 subsets and four iterations . in order to improve the anatomical localization of fdg uptake in the brain , computed tomography ( ct )\nthe ct images were acquired with 70 kvp , 500 a , and 200 msec exposure times for each step ( inveon ; siemens healthcare ) .\ncone - beam reconstruction was performed with four down - sample factors using bilinear interpolation and shepp.logan filters as previously described . in order to demonstrate the influence of the harderian gland on fdg uptake in specific brain regions , statistical parametric mapping ( spm5 ; wellcome trust centre for neuroimaging institute of neurology , uk )\npet images were realigned to a template image so that the static bounding box could be used to tightly crop the region of interest .\nthe template image was created from the mean image , which was realigned and provided an average representation of all images .\nthe normalize function determines the transformation that minimizes the differences between two images by minimizing the sum of squares of intensity differences . during normalization ,\n16 nonlinear warping iterations and trilinear interpolation of the images were performed . to improve normalization accuracy , we used a full affine transformation and nonlinear deformations , which facilitate the correction of subtle differences between subjects .\nglobal calculation was performed using standard mean voxel values . using this method , voxels with values less than 1/8 of the overall mean value were deemed extracranial . for the statistical analysis\n, we defined t contrast and p value adjustments to the control associated with significantly active regions and rest regions ( p < 0.005 ) . in order to compare regional standard uptake values ( suvs ) affected by ha ,\nsuv from brain regions including areas of removed harderian glands , frontal brain and the cerebellum were measured .\nthen the changes of suvs of the regions in relation to postoperative time were statistically analyzed using one - way anova and post - hoc analysis ( prism ver .\nwhen the last pet / ct scan was completed on postoperative day 30 , a visual limb - placing test was performed to evaluate visual acuity and determine if any complication had arisen following the ha .\nthe whisker - clipped mice were lifted by the tail over the wire bar lid of a mouse cage to a height of 20 cm and then lowered onto the lid within a second .\nmice with normal vision extended their forelimbs toward the lid before their noses reached it .\nthe ha mice recovered from surgery without any postoperative complications and the incision site healed without suturing .\nall adenectomized mice were found to have normal visual acuity according to the visual placing test , indicating there were no surgical complications .\nstrong fdg uptake of the harderian gland was observed in the intact side and radioactive spillover into the brain was also apparent ( fig .\nthis result suggests that excess signals emitted from the harderian gland interfere with the net measurement of brain fdg uptake , especially in the frontal brain region .\nbilateral ha efficiently eliminated extracranial accumulation of fdg in the harderian gland and subsequent radioactive spillover into the brain ( fig .\n3 ) . in particular , pet images of the ha mice showed more defined frontal regions of the brain than those of mice that did not undergo ha .\nanalyses of suvs revealed significant reductions in the regions of harderian gland and frontal brain ( fig .\nafter bilateral ha , fdg uptake in the regions of the removed harderian glands was significantly reduced starting on postoperative day 5 ( figs .\nthe reduction in fdg uptake was approximately 55% , and the left and right harderian glands both showed similar levels of reduction .\nsuvs for the frontal brain region decreased significantly from postoperative day 10 since harderian gland fdg accumulation was eliminated ( fig .\nwe also measured suvs for the cerebellum and the entire brain region but no statistical differences were found ( fig .\nthese results indicate that the effect of the harderian gland on fdg - pet analysis was limited to the frontal brain region .\nto localize the brain regions affected by harderian gland fdg uptake , we carried out a statistical analysis using the spm tool .\nwe were able to obtain parametric maps for mice with intact harderian glands and the adenectomized animals . when parametric maps were overlaid on a pet template , regions that had significantly high fdg uptake ( fig .\nresults of the spm analysis concur with those obtained for manually measured suvs ( figs .\nour study demonstrates that ha in mice is a simple and effective method which enables accurate measurement of fdg uptake in the frontal brain region .\nwe found that the surgical procedure used for rat ha was equally effective in mice although more caution is required for successful surgeries in the latter species .\nfor instance , bleeding must be strictly controlled because blood obstructs views of the limited surgical area that is available in mice .\nthe shape of the resected harderian glands should be carefully checked to avoid potential tearing during resection .\nthis is because any residual harderian gland left behind may result in an inaccurate fdg uptake reading along with the additional concern that the gland will regenerate .\nmoreover , the remaining tissue may cause inflammation that in turn could increase fdg uptake over a short - term period . the simple surgical procedure performed in our study\ncan be carried out by non - veterinarians and should take no more than 5 min . if the surgery is successful , the animal should recover readily without any postsurgical complications including vision impairment . a limitation associated with fdg - pet scanning\nis known as the \" partial volume effect \" , which stems from the finite spatial resolution of the images during sampling and reconstruction .\na partial volume effect can distort both the contour and signal intensity of images for an actual subject .\ndue to the partial volume effect , small pieces of tissues that accumulate high level of fdg such as harderian glands could appear larger than the actual size and obscure images of the brain during pet imaging .\ninterference attributed to harderian gland radioactive spillover in the rodent brain has previously been described in rats and mice .\nthus , the adverse effects of harderian gland fdg uptake are an unavoidable issue since anesthesia is essential for obtaining pet scans of rodents .\nwe found that ha in mice was feasible and had the same effect as it did in rats .\nafter ha , strong fdg uptake signals were excluded from the regions of the gland and distorted fdg - pet images were corrected .\nit should be pointed out that it took at least 10 days before significant differences in suvs were achieved .\nwe were also interested in assessing the range of signal spillover in the brain due to harderian gland fdg uptake .\nusing spm analysis , we were able to demonstrate the additive effect that the harderian gland has on measuring fdg uptake in the frontal brain region .\nour results support a previous finding that fdg uptake by the harderian gland results in a slight over - estimation of fdg uptake in the frontal lobe of rats .\nwe found that the level of fdg uptake stabilized starting 10 days after the surgery and was maintained for the remainder of the study .\nthis result suggests that the glandular tissue did not regenerate , which is important for long - term experiments . in conclusion\nwhen performed prior to pet scanning of mice brains , ha may be useful for visualizing the frontal lobe with 18f - fdg micro pet / ct imaging .", "answer": "positron emission tomography ( pet ) using 2-deoxy-2-[18f ] fluoro - d - glucose ( fdg ) as a radioactive tracer is a useful technique for in vivo brain imaging . \n however , the anatomical and physiological features of the harderian gland limit the use of fdg - pet imaging in the mouse brain . \n the gland shows strong fdg uptake , which in turn results in distorted pet images of the frontal brain region . \n the purpose of this study was to determine if a simple surgical procedure to remove the harderian gland prior to pet imaging of mouse brains could reduce or eliminate fdg uptake . \n measurement of fdg uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact harderian gland distorts frontal brain region images . \n spatial parametric measurement analysis demonstrated that the presence of the harderian gland could prevent accurate assessment of brain pet imaging . \n bilateral harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative day 10 . \n harderian adenectomy did not cause any post - operative complications during the experimental period . \n these findings demonstrate the benefits of performing a harderian adenectomy prior to pet imaging of mouse brains .", "id": 802} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSirtuin 2 Regulates Protein LactoylLys Modifications\n\nPaper sections:\n\nPost-translational modifications (PTMs) expand the functional proteome by regulating enzyme structure and function.[1] Many PTMs are derived from intermediates produced during cell metabolism and can serve as sensors for metabolic feedback providing proper nutrients to maintain cell growth and homeostasis.[1b, 1c] Due to their critical role in preserving homeostasis, site-specificity and abundance are tightly regulated, often through enzymatic addition ('writers') and removal ('erasers')[1c]. Mounting evidence, however, points to significant roles for non-enzymatic PTMs in the regulation of transcription, metabolism, and signaling.[2] We recently identified a PTM derived from the glyoxalase cycle intermediate, lactoylglutathione (LGSH) (Figure 1).[2b] When glycolytic flux exceeds the capacity of the glyoxalase cycle, glyoxalase 2 (GLO2), the rate limiting enzyme, becomes overwhelmed resulting in the accumulation of LGSH and subsequent non-enzymatic acylation of protein Lys residues (i.e. lactoylLys) (Figure 1).[2b] This modification is enriched on glycolytic enzymes, serving as a negative feedback mechanism for glycolysis.[2b] Coinciding with our report, Zhang, et al. observed lactoylLys modifications on histones, linking this modification to inflammatory signaling.[3]
Due to the novelty of this PTM, little is known about their regulation. With the non-enzymatic acyl-transfer mechanism defined in our report[2b] lactoylLys modifications would presumably accumulate in the absence of a dedicated 'eraser' protein. Thus, we hypothesized that a molecular 'eraser' protein(s) must exist for this PTM. LactoylLys modifications contain the necessary acyl-moiety required for the deacylase enzymes, sirtuins.[2b] Sirtuins play a role in both metabolism and inflammation through the regulation of Lys PTMs.[4] The sirtuin family is comprised of seven NAD+-dependent enzymatic deacylases (SIRT1-7), defined broadly by their subcellular localization (Figure 2A).[5] As we previously reported, our proteomic inventory of lactoylLys-modified proteins revealed an enrichment for glycolytic enzymes,[2b] suggesting the cytosolic sirtuins (SIRT1 and SIRT2) as potential candidates for a lactoylLys eraser. SIRT2 recognizes a more diverse group of substrates; furthermore, SIRT2 plays a regulatory role in both glycolysis and inflammation.[4a-c, 5a, 6] While SIRT2 is primarily localized to the cytosol in cells, it can translocate to the nucleus to interact with acylated chromatin.[5, 6b, 7] This substrate promiscuity and subcellular localization make SIRT2 a likely enzymatic deacylase for lactoylLys modifications.
To investigate this hypothesis, we screened the activity of recombinant sirtuins (SIRT1-7) against a lactoylated peptide from a known lactoylated protein, pyruvate kinase M2 (PKM2) (Figure 2B).[2b] This Lys residue (EIPAE-K*-VFLAQ) is also reported to be acetylated and regulated by SIRT2.[6a] The acyl transfer from LGSH to Lys residues defined in our previous work occurs at the carbonyl carbon rather than at the chiral carbon; thus, we predict the lactoylLys modification outlined in our report is generated in the D orientation in the same manner as D-lactate formation.[2b] In contrast, the hypothesized mechanism reported by Zhao et al. suggests enzymatic addition through L-lactyl-CoA, thus yielding L-lactoylLys modifications.[3]
As shown in Figure 2B, SIRT1, 2, 3, and 5 removed their canonical acetylated peptide. The L- enantiomer of lactoylLys, however, displayed significantly reduced removal with SIRT1 and 5 while SIRT2 was able to remove the L-enantiomer. In contrast, all SIRTs displayed minimal activity towards the D-enantiomer. To control for non-enzymatic hydrolysis of the acyl moiety, peptides were incubated without recombinant enzyme (CTRL, Figure 2B) or without NAD+ (Figure S1). A kinetic analysis confirms these findings; SIRT2 catalyzes the deacylation of the acetyl peptide at a faster rate than the lactoylated peptides (Figure 2C, S2). In further support of Figure 2B, SIRT2 displayed a greater propensity for the L-enantiomer vs the D-enantiomer, whereby steady-state could not be achieved, resulting in a large Km and standard error (Figure 2C, S2). This data suggests that SIRT2 is capable of removing the L- enantiomer suggesting this to be the predominant form in vivo. Further investigation is needed to determine the enantiomeric species generated from this non-enzymatic acyl transfer from LGSH.
To further investigate the interaction of SIRT2 and lactoylLys, we performed molecular docking experiments (Figure 3). This docking provides in silico insight into the enantiomeric preference of SIRT2 for lactoylated substrates. Unsurprisingly, docking of an acetylLys peptide to the catalytic pocket of SIRT2 results in the acetyl group being placed in a catalytically competent conformation. The acetyl oxygen points toward NAD+, able to attack the C1' of the nicotinamide ribose ring with a distance of 4.3 \u00c5 (Figure 3A). Docking of this peptide modified with L-lactoylLys results in the same catalytically favorable conformation for the L-lactoyl group, with the oxygen of the lactoyl carbonyl also oriented toward the nicotinamide ribose ring of NAD+ with a distance of 4.1 \u00c5 (Figure 3B). However, molecular docking of the D-lactoylLys peptide results in a different orientation within the catalytic pocket of SIRT2 with the oxygen of the lactoyl carbonyl 6.4 \u00c5 from the C1' of the nicotinamide ribose ring of NAD+. D-lactoylLys is positioned with the lactoyl hydroxyl pointing toward NAD+ and the oxygen of the lactoyl carbonyl pointing away from the nicotinamide ribose ring of NAD+ (Figure 3C), resulting in a conformation that is catalytically incompetent for deacylation. The positioning of the lactoyl group within the catalytic pocket of SIRT2 may explain the enhanced propensity for deacylation of L- over D-lactoylLys by SIRT2.
LactoylLys PTMs are dependent on the intracellular concentrations of LGSH.[2b] As GLO2 is the only reported enzyme to hydrolyze LGSH,[8] we generated SIRT2\u2212/\u2212 cell lines in wildtype (WT) and GLO2\u2212/\u2212 HEK293 cells using CRISPR-Cas9 (Figure 4A).[2b] To evaluate the abundance of lactoylated PTMs in each cohort, we performed reactivity-based protein profiling using an alkyne analog of methylglyoxal (aMGO).[9] Cells were treated with 50 \u03bcM aMGO for 6h, which is consistent with our previous report.[2b] An evaluation of whole cell lysates reveals protein labeling in GLO2\u2212/\u2212 cells. Cells lacking both GLO2 and SIRT2, however, displayed a marked elevation over GLO2\u2212/\u2212 alone (Figure 4B). These effects are more pronounced in chromatin fractions isolated from each cohort, indicative of tighter SIRT2 regulation on chromatin (Figure 4C).
Lastly, to quantify elevated abundance of lactoylLys in the SIRT2\u2212/\u2212/GLO2\u2212/\u2212 cell line we used stable isotope labeling of amino acids in cell culture (SILAC) and QuARKMod (a method for the quantitative analysis of arginine (R) and lysine (K) modifications)[2b, 10] in cells treated with high glucose (25 mM, Figure 4D). GLO2\u2212/\u2212 cells were cultured in 'heavy' media containing 13C615N2 Lys and 13C615N4 Arg and SIRT2\u2212/\u2212/GLO2\u2212/\u2212 cells were cultured in 'light' media containing natural abundance isotope amino acids. Both cell lines were treated with high glucose to evaluate the impact of lactoylLys PTMs in the context of increased glycolytic flux. As shown in Figure 4E, SIRT2\u2212/\u2212/GLO2\u2212/\u2212 cells have a 5.4-fold elevation in lactoylLys modifications and no significant changes in the MGO derived modifications CEL, MG-H, and CEA compared to GLO2\u2212/\u2212 cells indicating SIRT2's role as an eraser of lactoylLys PTMs.
Here, we present the first report of a lactoylLys eraser. LactoylLys modifications play regulatory roles in situations of elevated glycolytic flux, which are found in both hyperglycemic and inflammatory states.[2b, 3] SIRT2 regulates a diverse array of physiological and pathophysiological processes, including inflammation, response to infections, cell metabolism, ageing, cell structure, oxidative stress, and neurological disorders.[4, 11] Consistent with a lack of lactoylLys modifications on histones in our published proteomic inventory,[2b] our results show only SIRT2\u2212/\u2212/GLO2\u2212/\u2212 chromatin have dramatically elevated levels of labeled proteins, indicating tighter regulation by SIRT2 on chromatin. In addition to acetylation, SIRT2 regulates Lys benzoylation and 4-oxo-2-nonenal modifications on histones, further indicating a role for SIRT2 PTM regulation at the chromatin level.[12] Collectively, these data provide evidence for the enzymatic regulation of non-enzymatically-derived protein PTMs. Future work will be dedicated to identifying the site-specificity of this regulation in vitro and in vivo.
", "answer": "Post-translational modifications (PTMs) play roles in both physiological and pathophysiological processes through the regulation of enzyme structure and function. We recently identified a novel PTM, lactoylLys, derived through a non-enzymatic mechanism from the glycolytic by-product, lactoylglutathione. Under physiologic scenarios, glyoxalase 2 prevents the accumulation of lactoylglutathione and thus lactoylLys modifications. What dictates the site-specificity and abundance of lactoylLys PTMs, however, remains unknown. Here, we report sirtuin 2 as a lactoylLys eraser. Using chemical biology and CRISPR-Cas9, we show that SIRT2 controls the abundance of this PTM both globally and on chromatin. These results address a major gap in our understanding of how non-enzymatic PTMs are regulated and controlled.", "id": 803} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 72-year - old patient who had undergone bilateral uneventful cataract surgery 6 years ago , presented with visual loss in her left eye .\npatient had a medical history of multiple intravitreal and periocular steroid injections for the treatment of recalcitrant uveitis that was diagnosed 21 years ago .\nher visual acuity decreased to hand motion in left eye , and slit - lamp biomicroscopy revealed in - the - bag iol with an intact posterior capsule , and severe flare in the anterior chamber .\nan unclear image of macular edema was hardly detected on flourescein angiography ( fa ) that revealed flue images of posterior - segment obscured by media opacity .\nafter obtaining a signed informed consent , we scheduled to perform the intravitreal ozurdex application under the sterile conditions of the operation room .\na drop of 0.5% topical proparacaine hydrochloride with a drop of 5% povidone iodine was installed before the patient underwent an uncomplicated intravitreal dexamethasone implant application .\nafter significant regression of inflammatory cells secondary to uveitis , mild macular edema and an epiretinal membrane were precisely demonstrated with both optical coherence tomography and fa at 2 weeks after ozurdex application . on the postoperative 5 week , best corrected visual acuity ( bcva ) was improved to 0.4 logmar , and slit - lamp examination revealed the implant mislocated just behind the iol in an intact capsular bag , although there was no reaction in the anterior chamber , and no corneal edema was observed [ fig\nit was thought that such implant anteriorly migrated toward into the posterior chamber through weak zonules in the present case as she had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol .\nslit - lamp biomicroscopy revealed the dexamethasone implant mislocated just behind the intraocular lens in an intact capsular bag , and localized in the lower center of the visual axis ( white arrow ) any repositioning procedure was not considered since no sign of corneal edema or iop rise was present , as well as patient did not have any complaints although dexamethasone implant mislocated in the lower center of the visual axis .\nclose follow - up was scheduled for the case in order to find out any signs of anterior segment pathology . in the affected eye ,\nbcva and iop were found as 0.5 logmar and 17 mmhg with a quiescent anterior chamber and a clear cornea at the 4 month of postoperative follow - up , besides dexamethasone implant completely degraded .\nsteroid - induced ocular complications such as cataract formation and iop elevation have been more commonly reported according to the accelerating ozurdex application in the treatment of macular edema .\nanterior migration of dexamethasone implant has also been published as a rare complication in the literature .\nmigration of ozurdex into the anterior chamber was firstly described by pardo - lpez et al . in a patient with iris fixated iol .\nafter the patient had been referred with blurred vision in his left eye at the postoperative 3 week , authors noticed anterior migration of the implant with a diffuse corneal edema .\npatient had to be undergone corneal transplantation since corneal edema did not resolve even though surgical removal of the implant from the anterior chamber was performed .\njonas and schmidbauer reported dislocation of a steroid implant into the anterior chamber in an aphakic vitrectomized eye .\nvela et al . also reported the migration of ozurdex into the anterior chamber in a patient who previously underwent cataract surgery with iris - claw iol implantation .\nthe anterior migration of the ozurdex implant can cause complications such as secondary corneal decompensation . in these cases ,\nbansal et al . published the migration of the implant into the anterior chamber in three noninfectious posterior uveitic eyes with the history of postlensectomy - vitrectomy aphakia .\nauthors reported that the implant was relocated in the vitreous cavity in two of the cases .\nnonsurgical management of a dislocated dexamethasone implant into the anterior chamber with supine positioning after pharmacologic pupillary dilation was described by kishore and schaal .\npublished the scleral fixation of dexamethasone intravitreal implant with 10 - 0 nonabsorbable polypropylene suture in an angle - supported iol implanted case in order to prevent the risk of anterior segment complications associated with the migration of such implant into the anterior chamber .\nit was recommended that dexamethasone implant which migrated into the anterior chamber ought to be removed as soon as possible in cases with incipient corneal edema .\non the other hand , no corneal edema was reported in patients with late migration of such intravitreally injected implant .\nmentioned that only the patients in whom dexamethasone implant anteriorly migrated into the anterior chamber within 3 weeks after the intravitreal application developed corneal edema in their series .\nany sign of corneal edema also did not occur in our case who was faced with the anterior migration of such implant 5 weeks after the uncomplicated intravitreal application .\nanterior migration of a dexamethasone implant in eyes without perfect zonular or the posterior capsular integrity after cataract surgery , and with a history of the prior vitrectomy has been well - defined .\nreported five patients with an anteriorly migrated dexamethasone implant despite within the same lens and capsular status , although they had previous uncomplicated dexamethasone implant injections without any anterior chamber migration .\nanterior migration of a dexamethasone posterior implant into the anterior chamber through weak zonules was also described in cases with intact posterior capsule .\nimplant was surgically removed from the anterior chamber immediately by daudin and brzin , however turaka et al . reported that , without any surgical intervention , implant was spontaneously relocated back into the vitreous cavity with significant resolution of the corneal edema .\nherein , we report the first case with anterior migration of a dexamethasone intravitreal implant that mislocated just behind the iol in an intact capsular bag . in the present case ,\nthe migrated implant was well tolerated as there was no sign of the corneal complication , iop rise , and anterior chamber reaction .\nas this is a report of unique case with short follow - up , it is very difficult to comment that mislocation of a dexamethasone intravitreal implant on an intact posterior capsule is an innocent complication .\nit is mandatory to observe more cases with long follow - up in order to estimate possible side effects of ozurdex implant attached on the posterior capsule .", "answer": "intravitreal application of ozurdex ( allergan , inc . , irvine , ca , usa ) which is a biodegradable , \n sustained - release dexamethasone implant has been reported to be effective in the treatment of macular edema . \n migration of such implant into the anterior chamber has been recently described in cases without perfect zonular or the posterior capsular integrity . \n herein , we report the first case with anterior migration of ozurdex implant that mislocated just behind the intraocular lens ( iol ) in an intact capsular bag . \n it is thought that such implant migrated anteriorly towards into the posterior chamber through weak zonules as the present case had a medical history of uneventful phacoemulsification surgery with the implantation of posterior chamber iol . \n however , the migrated implant was well tolerated since there was no sign of the corneal complication , rise in intraocular pressure , and anterior chamber reaction . \n close follow - up was scheduled to find out any signs of anterior segment pathology . \n meanwhile dexamethasone implant completely degraded at the 4th month of postoperative follow - up .", "id": 804} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nependymomas are relatively rare neuroepithelial tumors and account for 3 to 7% of all central nervous system tumors .\nthe incidence of ependymomas is more frequent in children , and 50% occur in children < 5 years of age .\ninfratentorial locations of ependymomas are more frequent in infants and childhood , whereas supratentorial ependymomas are more often seen in adults.1 ependymal tumors are closely related to the ventricular system and central canal .\nthey can be observed extradurally in the sacral region and in the subarachnoidal space of the hemispheres . the most common location for infratentorial ependymomas is inside the fourth ventricle.2 \n the clinical signs and symptoms of intracranial ependymomas depend on the location , size of the tumor , and the age of the patient .\nthe symptoms in posterior fossa ependymomas are related to increased intracranial pressure from hydrocephalus caused by obstruction of the fourth ventricle .\nataxia , dizziness , hemiparesis , and visual disturbance may add to the clinical picture.1 \n 2 \n the current imaging protocol for the diagnosis is magnetic resonance imaging ( mri ) .\nthe most characteristic finding on mri is a downward extrusion of the tumor through the foramen of magendie into the cervical subarachnoid cervical space or through the foramen of luschka into the cerebellopontine cistern.3 \n 4 this presentation highlights the requirement for close follow - up of grade ii ependymomas for anaplastic transformation .\nhis eyes were open spontaneously ; however , his left eye was looking at medial and downside , and his left eye gaze was limited to upside and lateral .\nan infratentorial brain tumor in the median and right cerebellar area was found on contrast mri .\naxial initial magnetic resonance imaging scans show posterior fossa mass filled in fourth ventricle ( a ) with nonhomogeneous slight contrast enhancement ( b ) .\nsevere hydrocephalus can be seen with temporal horn filling secondary to the obstruction of the fourth ventricle .\npostoperative axial ( c ) and coronal contrasted images ( d ) show complete resection of the mass with opening of the fourth ventricle and relaxation of the temporal horns .\nthe patient presented with vomiting and visual disturbance to the pediatric emergency department 12 months later .\non the second operation , the tumor was hard to aspirate with the cavitron ultrasonic surgical aspirator ( sonoca 400 , sring gmbh , quickborn , germany ) and was adherent to the brainstem and lower cranial nerves . only subtotal extirpation could be achieved ( fig .\nthe recurrent tumor showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopalisading ( fig .\n3 ) . \n postcontrast axial ( a ) and coronal ( b ) images show regrowth of the mass lesion with strong contrast uptake .\n( a ) moderately cellular tumor composed of monomorphic cells with round to oval nuclei containing salt and pepper pattern of chromatin .\nradially arranged ependymal cell processes become thinner toward the vascular wall leaving an acellular zone around the blood vessel , called \nperivascular pseudorosette , a key histologic feature for ependymoma ( hematoxylin and eosin [ h&e ] 100 ) . after the second operation ( b )\nabundant endothelial proliferation , microvascular proliferation , hypercellularity with nuclear hyperchromasia , pleomorphism , numerous mitoses , and pseudopalisading necrosis warrants a diagnosis of anaplastic ependymoma when seen throughout the lesion ( h&e 200 ) .\nmoreover ( c ) , focus of coagulative necrosis , nuclear pseudopalisading was prominent around the necrotic areas , tumor cells oriented closer to viable areas emphasizing anaplastic changes ( h&e 200 ) .\nki-67 immunolabeling index is an independent prognostic factor and accurate predictor of outcome in patients with intracranial ependymoma ( d ) .\nthe index was 10% in the first operation that increased to 35% for our case in this image ( ki-67 200 ) .\nbailey and cushing recognized ependymomas as an independent entity in their first brain tumor classification in 1926 .\nvariants were subsequently established . the most recent world health organization ( who ) classification identified four variants of ependymal tumors in addition to three grades of malignancy.5 \n 6 these four variants are myxopapillary ependymoma , subependymoma , tanycytic ependymoma , and clear cell ependymoma.3 \n 6 \n 7 \n myxopapillary ependymomas and subependymomas are slow - growing tumors classified as grade i. both lesions are easily recognizable lesions ;\ngrade iii ependymomas have increased cellularity and brisk mitotic activity , often associated with microvascular proliferation and pseudo palisading necrosis . \ntheir results showed that poor clinical results paralleled histopathologic grade.8 \n the outcome of children with intracranial ependymomas has improved significantly during the last few years .\nrecent reports demonstrate a 5-year overall survival rate not more than 40 to 65% in children with intracranial ependymomas.9 \n 10 \n 11 \n 12 pediatric oncology group findings suggest that the poor survival estimates frequently reported for infants are most likely related to the higher incidence of infratentorial tumors , the lower rate of complete resection , and the delay of the administration of radiation therapy.13 \n the extent of surgical resection appears to be the other important prognostic factor in outcome for children with intracranial ependymomas . in patients with complete removal , 5-year survival is 67 to 80% ; 5-year progression - free survival is 51 to 75%.14 \n 15 \n 16 \n studies have shown that patients with ependymoma who receive radiation therapy have a better outcome than who are not treated with irradiation.17 \n 18 however , there is no standard protocol for optimal management for children with intracranial ependymomas .\ntotal / near - total surgical resection with an acceptable neurologic outcome combined with postoperative radiation therapy is the current treatment modality .\nimmediate postoperative irradiation is not widely accepted in the treatment of children < 3 years of age .\nstereotactic radiosurgery has been applied to manage recurrent or residual intracranial tumor in some institutions .\nsome reports described that adjuvant chemotherapy did not influence survival of patient with anaplastic ependymomas.18 \n 19 \n 20 \n the most common location for infratentorial ependymoma is within the fourth ventricle .\nthe selected surgical approach may be a suboccipital craniotomy with or without c1 laminectomy depending on the extension of the tumor in the cervical region .\nsurgical resection appears to the most important prognostic factor ; therefore the best effort to perform total or near - total resection should be made.21 \n 22 \n in conclusion , the ependymomas of the children are difficult to control , and surgical removal remains the mainstay of the treatment . despite a gross total resection ,\nthe correct grading of intracranial ependymomas may be difficult for the anaplastic variant because the common criteria for anaplasia are not completely reliable for all cases.13 \n 22 ependymomas in young infants have a worse prognosis than older children , so we need a grading scheme with a proven general ability to distinguish grades and to predict the evolution of individual cases.23 also new radiation therapy techniques and chemotherapeutic agents need to be developed .\npostoperative irradiation is not recommended in the treatment of grade ii ependymomas for children < 3 years of age .", "answer": "ependymomas are central nervous system neoplasms that account for a third of all posterior fossa tumors in children . the most common location for infratentorial ependymoma is within the fourth ventricle . \n we present a case report of malignant transformation of an infratentorial grade ii ependymoma in a 2-year - old child who presented with vomiting and visual disturbance . \n an infratentorial brain tumor in the left cerebellar area was totally removed , and the initial pathologic diagnosis was grade ii ependymoma . \n the tumor recurred aggressively 1 year later ; subtotal removal and adjuvant chemotherapy were performed . after a second operation , a histopathologic study was performed . \n the second specimen was defined as a grade iii anaplastic ependymoma . \n transformation to grade iii anaplastic ependymoma is possible for a grade ii ependymoma but very rare . \n the diagnosis of the anaplastic variant of intracranial ependymomas is difficult . \n surgical treatment remains the mainstay of the treatment for all cases . \n ependymomas in young infants have a worse prognosis than older children , so we need individual clinical evaluation and close follow - up of such cases . \n this article highlights the requirement of a close follow - up for grade ii ependymomas for anaplastic transformation .", "id": 805} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhemorrhage after percutaneous nephrolithotomy ( pcnl ) is a significant complication that occurs in a small percentage of cases .\nhowever , arterial injuries sometimes require transarterial embolization to control the refractory bleeding . in patient presenting with refractory bleeding ,\npseudoaneurysm formation is the most common cause with a reported incidence of 0.6 - 1% .\nwe report a case of early erosion of an embolization coil from the renal vasculature into the urinary collecting system causing urinary tract obstruction and urosepsis .\na 23-year - old male underwent left urs and pcnl for a left upper ureteric calculus and a 2.5-cm lower pole renal calculus in a community hospital in december , 2010 .\none week after nephrostomy tube removal , the patient experienced gross hematuria with clot retention .\nthe patient underwent endoscopic bladder clot evacuation and dj stent removal in the same hospital .\ntwo weeks later , again he developed gross hematuria with fever and a significant decrease in hematocrit .\nafter resuscitation the patient was referred to our centre . on angiography , there was a pseudoaneurysm in the lower segmental renal artery .\nafter 3 months of embolization , the patient presented with high - grade fever , left flank pain and burning micturiton . on x - ray kub 2 coils were seen in left renal area , whereas 1 coil was seen in l3 transverse process area .\naxial noncontrast and contrast - enhanced ct images showed left hydronephrosis with dilated upper ureter and an embolization coil in the upper ureter [ figure 1 ] .\nx ray kub shows 2 coils in left renal area , 1 coil in l3 transverse process area .\nct urogram shows left hydronephrosis with dilated upper ureter and 2 coils in left kidney & 1 coil in upper ureter\nin 1975 , angioembolization for renal pseudoaneurysm was reported in a human patient when an autologous blood clot was used to embolize a bleeding pseudoaneurysm as a temporary measure before nephrectomy .\nwe found only three case reports in which embolization coil migrated to the collecting system.[810 ] in all these case reports the coil eroded after 1 year following embolization .\nall the three patients presented with hematuria and renal colic . in our case , patient presented early ( 3 months ) with complaints of renal colic and persistent fever after coil embolization . hypothetically three mechanisms of coil erosion have been proposed .\nfirst , the diameter of arteriocaliceal communication might be larger than the embolization coil , and the coil gets extruded through the communication soon after placement .\nsecond , the arteriocaliceal communication could get dilated over time because of inflammation due to infection or the constant irritation from the indwelling coil itself , leading to eventual erosion into the collecting system .\nfinally , rupture of the weakened wall of a pseudoaneurysm exposed to high arterial pressure may lead to erosion . according to the first hypothesis ,\nif the arteriocaliceal communication was larger than the embolization coil than all three coils would have extruded through the communication and gross hematuria would have reappeared .\nthe third mechanism would have lead to massive hematuria in addition to the coil migration . in this case\nthe patient presented with high - grade fever and left flank pain but not hematuria .\ntherefore in this case the second mechanism seems to be the most likely cause of erosion of the embolization coil .\none of the important but rare causes of urinary tract obstruction is the migration of embolization coil into urinary collecting system .", "answer": "refractory bleeding following percutaneous nephrolithotomy ( pcnl ) is mainly due to formation of pseudoaneurysm . \n transarterial embolization is required to control the bleeding in such cases . \n we report a case of post - pcnl hematuria in whom angioembolization was done . \n an early erosion of the embolization coil from the renal vasculature into the urinary collecting system occurred , causing urinary tract obstruction and urinary tract infection ( uti ) . \n the coil was retrieved ureteroscopically after control of uti with antibiotics . \n migration of embolization coil into urinary collecting system is a rare but important cause of urinary tract obstruction . \n the treating physician as well as the patient should be aware of this complication .", "id": 806} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe world health organization has defined health literacy ( hl ) as the cognitive and social abilities which determine the incentive and ability of individuals to increase access to understand and use information in ways , which promote and preserve good health . \nthe hl of patients has obtained more attention as a risk factor for poor adherence to treatment and adverse outcomes in chronic disease 's management particular in diabetes care .\ndiabetes is the most common metabolic disease with a dramatic increase rate of prevalence throughout the world , which has an important impact on the public health and quality of life of the patients .\nthere is a developing frame of the literature that discovers the association between hl and health outcomes in people with diabetes .\nolder studies of low hl reported adverse effects on diabetes - related health outcomes ; however , more recent studies showed no association between hl levels and intensity , frequency or incidence of outcomes , and thus the effect of hl on the health of people with diabetes is yet unclear .\nbased on national reports , the prevalence of diabetes has been raised during three decades in iran and also a recent national survey about hl has shown that majority of people has inadequate knowledge .\nhowever , there are different tools to measure hl and numeracy skills in general population in different languages , only diabetes numeracy test-15 ( dnt-15 ) has been developed specifically to measure numeracy skills in patients with diabetes as first scale by huizinga et al .\n, in english language . with regard to lacking of appropriate measurement tool for patients with diabetes in persian ( farsi ) language , this study aimed to provide evidence for the psychometric properties of the iranian ( persian language ) version of dnt-15 .\nthe dnt was designed to evaluate nutrition , exercise , glucose monitoring , oral medication , and insulin skills that patients may encounter during daily diabetes self - management .\nblood - glucose monitoring skills are evaluated by three items about number hierarchy , glaciated hemoglobin , and calculating supplies needed .\neight items assess the oral medication use and insulin use . oral medication ( one question )\nuse refill patterns and dates , and oral titration schemes and insulin use ( seven questions ) including interpretation of syringes , correction or sliding - scale insulin use , insulin adjustment for carbohydrate intake , and titration instructions [ table 1 ] .\nitems are scored as binary outcomes correct or incorrect and no partial credit is given .\nmany patients with diabetes use calculators ; therefore , participants were allowed to use calculators during the administration of the dnt to emulate real - life circumstances .\ndnt scores are reported as percent correct ( with a possible range of 0% to be 100% ) .\ndescription of diabetes numeracy test items in this phase , the original questionnaire was translated by two independent health professionals from english to persian .\nafter translation , by consultation with the principal investigators , the results were rechecked . finally , they achieved a precision translation for the questionnaire . in this phase ,\nthe questionnaire that translated in the previous step , gave to two professional translators whose native language were english , and they are sufficient dominance in persian language .\nthe translators did not communicate with one another and did not know the original english version .\ntranslated versions by consultation with the principal investigators of conversion backward translation were combined . in this phase ,\na group of experts was reviewed , all phases , including verification and cross - cultural equivalent ( cross - cultural equivalence ) .\ncultural equivalent to the word ( semantic ) , a term equivalent ( idiomatic ) , and equivalent experience ( experiential ) , and conceptually equivalent ( conceptual ) were performed by an expert panel .\nthis group included experts in diabetes , certified diabetes educators , methodologist , primary care providers , and registered dietitians , behavioral researchers in diabetes , and literacy and numeracy experts . finally , the dnt was to address the clarity of items for patients with diabetes .\ninterviewees were asked specific questions about each item to evaluate the understandability of the wording .\nif an item was unclear , the interviewee was told the purpose of the item and then encouraged to suggest a different format or wording . in response to the interviews , the scale was reformatted and slightly reduced to the final 15-items .\nreliability was evaluated by internal consistency ( kuder - richardson 20 ) , and validity was evaluated through content validity ratio ( cvr ) and content validity index ( cvi ) .\na convenience sample of 120 patients with diabetes was interviewed in the diabetes clinic affiliated to institute of endocrinology and metabolismof an item at clinic visits . any person diagnosed with type 1 and or type 2 diabetes which was able to read ( at least eight grades ) and speak persian language .\npotential participants were excluded if they corrected visual acuity was > 20/50 using a rosenbaum pocket vision screener , or if they had a diagnosis of significant dementia , psychosis , or blindness .\nthe dnt was designed to evaluate nutrition , exercise , glucose monitoring , oral medication , and insulin skills that patients may encounter during daily diabetes self - management .\nblood - glucose monitoring skills are evaluated by three items about number hierarchy , glaciated hemoglobin , and calculating supplies needed .\neight items assess the oral medication use and insulin use . oral medication ( one question )\nuse refill patterns and dates , and oral titration schemes and insulin use ( seven questions ) including interpretation of syringes , correction or sliding - scale insulin use , insulin adjustment for carbohydrate intake , and titration instructions [ table 1 ] .\nitems are scored as binary outcomes correct or incorrect and no partial credit is given .\nmany patients with diabetes use calculators ; therefore , participants were allowed to use calculators during the administration of the dnt to emulate real - life circumstances .\ndnt scores are reported as percent correct ( with a possible range of 0% to be 100% ) .\nin this phase , the original questionnaire was translated by two independent health professionals from english to persian .\nin this phase , the questionnaire that translated in the previous step , gave to two professional translators whose native language were english , and they are sufficient dominance in persian language .\nthe translators did not communicate with one another and did not know the original english version .\nin this phase , a group of experts was reviewed , all phases , including verification and cross - cultural equivalent ( cross - cultural equivalence ) .\ncultural equivalent to the word ( semantic ) , a term equivalent ( idiomatic ) , and equivalent experience ( experiential ) , and conceptually equivalent ( conceptual ) were performed by an expert panel .\nthis group included experts in diabetes , certified diabetes educators , methodologist , primary care providers , and registered dietitians , behavioral researchers in diabetes , and literacy and numeracy experts . finally , the dnt was to address the clarity of items for patients with diabetes .\ninterviewees were asked specific questions about each item to evaluate the understandability of the wording . if an item was unclear , the interviewee was told the purpose of the item and then encouraged to suggest a different format or wording . in response to the interviews , the scale was reformatted and slightly reduced to the final 15-items .\nreliability was evaluated by internal consistency ( kuder - richardson 20 ) , and validity was evaluated through content validity ratio ( cvr ) and content validity index ( cvi ) .\na convenience sample of 120 patients with diabetes was interviewed in the diabetes clinic affiliated to institute of endocrinology and metabolismof an item at clinic visits . any person diagnosed with type 1 and or type 2 diabetes which was able to read ( at least eight grades ) and speak persian language .\npotential participants were excluded if they corrected visual acuity was > 20/50 using a rosenbaum pocket vision screener , or if they had a diagnosis of significant dementia , psychosis , or blindness .\ndifficult issues for participants included titration schemas , food label interpretation , insulin adjustment instructions , and items that required multi - step math ( e.g. , calculating insulin dosage based on carbohydrate intake and glucose level ) .\nquestions 2 , 5 , 6 , 7 , 8 , 9 , and 11 were answered accurately respectively by 89.1% , 78.2% , 87.4% , 72.3% , 85.7% , 84% , and 83% of participants for this study .\nhowever , questions 14 and 15 , which required patients to interpret a word problem and apply multiple numerical steps to determine their insulin dosage , was only answered correctly , respectively by 41% , 54% of the participants .\nthe 15-item persian version of the dnt has highly reliable , as determined by internal consistency kuder - richardson ( kr-20 = 0.90 ) .\ncontent validity was examined by the expert panel ( cvr : 089 and cvi : 0.86 ) .\nthe short version of the dnt-15 demonstrated internal consistency and construct validity in relation to reading skills in persian ( farsi ) language in iranian population .\nscores on the dnt-15 showed a direct correlation with level of education in this study which is consistent with other reports .\nalthough there have been some reports about hl in iran they were not specific about diabetes in iran .\nother studies have identified the role of hl techniques in the improvement of health outcomes in diabetes and congestive heart failure .\npatients with low hl may benefit from interventions that address numeracy , particularly in the setting of diabetes management .\nthe dnt-15 can provide a measurement of diabetes - specific numeracy and provide more information on the role of disease - specific numeracy in future studies .\nmore studies are needed to further understand the role of numeracy tailored interventions for the management of diabetes .\nfor example , study participants had a difficult time with the multi - step math required to calculate a correction dosage of insulin when instructions were presented as a sequence of sentences .\nthis item was encompassed to mirror clinical practice regarding how patients are currently instructed to take their insulin .\nthis example provides an important lesson for health care providers and educators in effective communication styles for all clinical care recommendations .\nthe persion ( farsi ) version of dnt-15 is a reliable and valid tool to measure of diabetes - specific numeracy skills for patients with diabetes .", "answer": "background : low health literacy ( hl ) of patients has obtained more attention as a risk factor for poor adherence to treatment and adverse outcomes in chronic disease 's management particular in diabetes care . \n diabetes numeracy test-15 ( dnt-15 ) has been developed specifically for this purpose . \n the objective of the current study is to evaluate psychometric properties of iranian ( persian ) version of the dnt-15.methods:the shortened version of the dnt ( 15-items ) was completed by 120 patients with diabetes . \n the kuder \n richardson formula 20 for internal consistency was conducted . \n content validity , criterion - related validity , and construct validity were also evaluated.results:the average score on the dnt was 72% and took an average of 25 minutes to complete . \n the dnt-15 had a very good internal reliability ( kr-20 = 0.90 ) and also content validity ( content validity ratio : 089 and content validity index : 0.86).conclusions : the dnt-15 ( persian version ) is a reliable and valid measure of diabetes - related numeracy skills for iranian patients with diabetes ; however , additional studies are needed to further explore the association between diabetes - specific numeracy and acculturation and their impact on diabetes - related outcomes in iranian population .", "id": 807} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na girl weighing 3,190 g was delivered by a caesarean section at 38 weeks and five days of gestation . at the time of birth , a systolic murmur\nwas noted during a physical examination , and transthoracic echocardiography revealed a peri - membranous ventricular septal defect ( vsd ) with a septal aneurysm , a small patent foramen ovale ( pfo ) , and a small right - sided patent ductus arteriosus ( pda ) from the innominate artery .\nthe vsd was measured as having a diameter of 3.5 mm and a shunt flow less than 2.5 m / sec .\ndue to the presence of neonatal hyperbilirubinemia , echoencephalography was conducted , and no abnormalities were found .\nfive months later , the patient was referred to konkuk university medical center for vsd and pda .\nher body weight was 6,700 g ( 25th percentile ) , and her height was 61.6 cm ( 10th percentile ) .\ntransthoracic echocardiography revealed a vsd approximately 6 mm in size with a minimal aneurysm , a left - sided pda 3.6 mm in diameter from the right aortic arch and an aberrant left subclavian artery .\na subsequent computed tomographic scan demonstrated isolation of the left subclavian artery with a right aortic arch , a left pda , and a vsd ( fig .\nthe intraoperative findings were a perimembranous vsd , a pfo , a mildly patent right ductus arteriosus , and isolation of the left subclavian artery connected to the left pulmonary artery via a left pda .\nthe left subclavian artery was disconnected from the left pulmonary artery and reimplanted to the left common carotid artery by end - to - side anastomosis with monofilament polypropylene 6 - 0 sutures ( fig .\nductus arteriosus is usually located on the left side , between the descending aorta and the junction of the main pulmonary artery and left pulmonary artery .\nhowever , ductus arteriosus may also be present on the right side or , very rarely , may occur bilaterally in association with aortic arch anomalies or conotruncal anomalies .\nin such aortic arch anomalies , isolation of the left subclavian artery with right aortic arch is also uncommon . here\n, isolation refers to the fact that the left subclavian artery connects to the pulmonary artery via either the ligamentum arteriosum or a patent ductus arteriosus without any connection to the aorta .\nisolation of the left subclavian artery with a right aortic arch is known to be commonly associated with congenital heart disease , but may also occur with normal intracardiac anatomy , although few such cases have been described .\nisolation of the left subclavian artery with a right aortic arch may be related to the 22q11 deletion .\nbilateral ductus arteriosus and isolation of the left subclavian artery with a right aortic arch can be explained through the hypothetical double aortic arch plan suggested by edward .\nregression takes place on two levels in the double aortic arch plan : on one level , regression occurs between the left common carotid artery and the left subclavian artery ; and on the other level , regression occurs at the left dorsal aortic root distal to the left ductus arteriosus .\nand then right ductus arteriosus remains persistent , left ductus arteriosus connects the left subclavian artery to the left pulmonary artery ( fig .\nhowever , the right ductus arteriosus regressed , and only the left ductus arteriosus remained patent .\nif the left ductus arteriosus is patent , blood may be supplied to the left subclavian artery via the left ductus arteriosus .\nif the left ductus arteriosus regresses , the blood supply to the left subclavian artery may involve a mediastinal , thoracic anastomosis , or vertebral pathway .\nisolation of the left subclavian artery usually presents with no apparent symptoms in neonates , but it may present with congenital pulmonary steal syndrome , subclavian steal syndrome , or may even present in adults with late symptoms due to sporadic progression .\nhayabuchi et al . reported the case of a three - month - old girl with cerebral atrophy and an underdeveloped left arm .\nreported the case of a 15-year - old boy with an underdeveloped left arm . due to these symptoms and signs ,\nthe therapeutic management of isolation of the left subclavian artery remains controversial , especially when it is associated with complicated congenital heart disease .\nsome authors have suggested that adequate collateral circulation must be ensured , meaning that reconstruction of the isolated subclavian artery is optional , regardless of the symptoms and signs .\nsuccessful results have been reported after ligation or device closure of the pda and ligation of the left subclavian artery .\nhowever , reconstruction of the left subclavian artery due to pulmonary steal syndrome after right pda closure in bilateral pda has been reported . in one report , ischemic symptoms in the left arm and vertebrobasilar insufficiency occurred years after ligation of the left subclavian artery .\nhokari et al . reported that a man with peutz - jeghers syndrome presented with his first vertigo attacks due to subclavian steal syndrome at 29 years of age .\nour patient presented with no symptoms and signs related to subclavian or pulmonary steal syndrome , and had shown normal findings on an echoencephalography study conducted at our medical center due to neonatal hyperbilirubinemia .\nhowever , brain computed tomography angiography performed after surgery revealed hypoplasia of the left vertebral artery .\nwe suggest that this hypoplasia would have led to vertebrobasilar insufficiency or underdevelopment of the left arm without surgical reconstruction .\nsince surgical reconstruction of the isolated left subclavian artery leads to antegrade flow in the left subclavian artery , it can prevent hypoplasia of the left vertebral artery and subclavian / pulmonary steal syndrome .\nour case shows that early surgical reconstruction is reasonable , regardless of the symptoms , in cases of isolation of the left subclavian artery .", "answer": "right aortic arch with isolation of the left subclavian artery is a rare anomaly . \n the incidence of bilateral ductus arteriosus is sporadic , and a right aortic arch with isolation of the left subclavian artery in association with bilateral ductus arteriosus is therefore extremely rare . \n since the symptoms and signs of isolation of the left subclavian artery can include the absence or underdevelopment of the left arm , subclavian steal syndrome , or pulmonary artery steal syndrome , the proper therapeutic approach is controversial . \n we report a case in which surgical reconstruction was used to treat isolation of the left subclavian artery with right aortic arch in association with bilateral ductus arteriosus and a ventricular septal defect .", "id": 808} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 73-year - old female was admitted for surgical removal of a left renal pelvic mass . she has taken antihypertensive agents for 30 years and received percutaneous coronary intervention due to stable angina 3 years ago . during routine follow - up , a renal mass was incidentally detected 2 months ago .\nlaboratory values revealed a marginal elevation of serum creatinine ( 1.21 mg / dl ) .\nthe ultrasonography showed an echogenic mass within the renal pelvis and mild dilation of several calyces .\nthe calcified lesion was not found on plain radiograph of the abdomen ( kidneys , ureters , and bladder ) .\nan abdominopelvic computed tomography revealed a noncalcified soft tissue mass in the left renal pelvis on precontrast enhancement scan .\nthe cut surface of the resected specimen revealed a 532 cm - sized , well - defined ovoid , cystic mass which was compactly filled with white and reddish tan - colored amorphous materials in the pelvis .\nhistologically , the cystic lumen contained multiple keratinous materials and much of the cystic lining epithelia were denuded .\n, santa cruz , ca , usa ) and cytokeratin 7 ( ck7 ) ( 1:100 ; dako , glostrup , denmark ) was performed to identify epithelium - specificdifferentiation .\nin contrast , most of the cells in the lining of squamous epithelia were negative for these urothelial specific antibodies .\nhowever , some portion of the squamous epithelia interestingly contained a few uroplakin - positive cells ( fig .\neven though the epidermoid cyst of the kidney is a very rare to be characterized , the typical features of the lesion can be summarized as follows .\nthe clinical symptoms are flank pain , gross hematuria , or lower urinary tract symptoms .\nthe calcified inhomogeneous lesion , combined renal stone , and previous renal surgery are other important clinical clues for the renal epidermoid cyst ( table 1 ) .\nto date , two cases of epidermoid cyst in the renal pelvis have been reported .\nthey also showed a typical calcified lesion combined with renal stone like other renal epidermoid cysts . with these reasons\n, it seemed hard to think of epidermoid cyst as a presumptive diagnosis before surgery in this case . to the best of our knowledge ,\nthis case of a noncalcified epidermoid cyst in the renal pelvis is the first report in the english literature .\nthe histology of a typical epidermal cyst that was lined by stratified squamous cells with laminated keratins .\nalthough epidermoid cyst of the skin is a common lesion resulted from implantation of epidermis into the dermis , histogenesis of epidermoid cyst in the kidney remains uncertain . as a possible histogenetic mechanism , either epidermal embryonic remnants of wolffian ducts or traumatic implantation of transformed epithelial cells during renal operation have been proposed .\nthe extension of squamous metaplastic changes from the upper ureter to the pelvocalyceal system in prolonged irritative condition induced mostly by stones is considered as the other plausible explanation .\nhowever , the cellular basis of squamous metaplasia is not fully understood in this rare condition .\nthe apical surface of urothelium is highly specialized as it is covered almost by urothelial plaques which are composed of uroplakins .\nfour uroplakins ( ia , ib , ii , and iii ) have been isolated and are considered to be biochemical markers of terminal urothelial differentiation .\nck7 is an intermediate filament proteins expressed in a wide variety of simple epithelia but not in the squamous epithelia .\nit is well known that vitamin a deficiency can induce keratinizing squamous metaplasia in a variety of epithelia including urothelium .\nthe urothelial keratinization in the vitamin a - deficient mice bladder occurred heterogeneously adjacent to areas lined with normal appearing urothelium .\nthe sharp boundary between the keratinized epithelium and the seemingly normal urothelium was maintained with no intermediated cells .\naccording to the our histologic examination , nearly almost of the urothelial cells in the cystic lining were positively stained against both uroplakin ii and ck7 , but most of the squamous epithelial cells were negative for these antibodies .\nthe two epithelia were sharply delineated and more distinctly distinguishable in the immunohistochemical stained sections .\nthese features were similar with heterogenous metaplasia of the animal urothelium in the previous study .\nhowever , some squamous epithelia contained a few uroplakin - positive cells and ck7-positive cells to some extent . even though the significance of few uroplakin expressions in squmous epithelium should be evaluated by other studies , is this an indirect evidence of the direct transformation of umbrella cells to squamous metaplasia or dedifferenctiation of metaplastic squamous epithelium to urothelium ?", "answer": "since the renal epidermoid cyst is too rare , the mechanisms of squamous morphogenesis have not well characterized . \n a 73-year - old female was referred with an incidentally detected renal pelvis mass . \n abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis . \n total nephroureterectomy was performed under the impression of a renal pelvis malignancy . \n the patient was discharged without postoperative complication . \n the outer surface of mass lesion was lined with urothelia and squamous epithelia , containing keratinous materials . \n the urothelia were positively stained against uroplakin ii and cytokeratin 7 , whereas almost of the squamous epithelia were negative with uroplakin ii . \n the two different epithelia were generally sharply demarcated . \n interestingly , some part of squamous epithelia contained uroplakin - positive and many more cytokeratin 7-positive cells . \n the atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before , and the unique immunohistochemical results may understand the histogenetic implications of the lesion .", "id": 809} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\neq . 2 can be generalized to the case where the charge moves continuously , corresponding to an infinite number of steps . if we makezi = qmax / n , i=1 n , vi = vo , i=1 n , then all i = , and we can write eq .\n4 can also be written as(5)qnor(v)=12[1+coth[qmax(vvo)2kt]2ktqmax(vv0)],which is of the same form of the classical equation of paramagnetism ( see kittel , 2005 ) .\ntypically , the experimental value of the charge plotted is normalized to its maximum because there is no knowledge of the absolute amount of charge per molecule and the number of molecules .\nthe normalized q - v curve , qnor , is obtained by dividing q(v ) by the sum of all the partial charges .\n1 shows qnor computed using eq . 2 for one , two , three , four , and six transitions and for the continuous case using eq .\n5 ( squares ) with superimposed fits to a two - state boltzmann distribution ( eq . 1 , lines ) .\nthe computations were done with equal charge in each step ( for a total charge qmax = 4e0 ) and also the same vi = 25 mv value for all the steps .\nit is clear that fits are quite acceptable for cases up to four transitions , but the fit significantly deviates in the continuous case .\nexamples of normalized q - v curves for a qmax = 4 computed with eq . 2 for the cases of one , two , three , four , and six transitions and the continuous case using eq . 5 ( squares ) .\nall the q - v curves were fitted with eq . 1 ( lines ) .\nthe insets show the fitted valence ( qmax ) and half - point ( v1/2 ) . considering that experimental data normally have significant scatter , it is then quite likely that the experimenter will accept the single - transition fit even for cases where there are six or more transitions ( see fig .\n1 ) . in general , the case up to four transitions will look as a very good fit , and the fitted qmax value may be inaccurately taken and the total charge transported might be underestimated . to illustrate how bad the estimate can be for these cases ,\nwe have included as insets the fitted value of qmax for the cases presented in fig .\nit is clear that the estimated value can be as low as a fourth of the real total charge .\nthe estimated value of v1/2 is very close to the correct value for all cases , but we have only considered cases in which all vi s are the same . it should be noted that if i of the rightmost transition is heavily biased to the last state ( vi is very negative ) , then the qmax estimated by fitting a two - state model is much closer to the total gating charge . in a three - state model , it can be shown that the fitted value is exact when v1 and v2 because in that case , it converts into a two - state model .\nalthough these values of v are unrealistic , the fitted value of qmax can be very close to the total charge when v2 is much more negative than v1 ( that is , v1 > > v2 ) .\non the other hand , if v1 < < v2 , the q - v curve will exhibit a plateau region and , as the difference between v1 and v2 decreases , the plateau becomes less obvious and the curve looks monotonic .\nthese cases have been discussed in detail for the two - transition model in lacroix et al .\nwe conclude that it is not possible to estimate unequivocally the gating charge per sensor from a single - boltzmann fit to a q - v curve of a charge moving in multiple transitions .\nthe estimated qmax value will be a low estimate of the gating charge qmax , except in the case of the two - state model or the case of a heavily biased late step , which are rare occurrences .\nit is then safer to call apparent gating charge the fitted qmax value of the single - boltzmann fit .\nthe most general case in which transitions between states include loops , branches , and steps can be derived directly from the partition function and follows the general thermodynamic treatment by sigg and bezanilla ( 1997 ) , chowdhury and chanda ( 2012 ) , and sigg ( 2013 ) .\nthe reaction coordinate is the charge moving in the general case where it evolves from q = 0 to q = qmax by means of steps , loops , or branches . in that case , the partition function is given by(6)z=iexp(qi(vvi)kt).we can compute the mean gating charge , also called the q - v curve , as(7)q(v)=q=ktzz = ktdlnzdv=iqiexp(qi(vvi)kt)iexp(qi(vvi)kt).the slope of the q - v is obtained by taking the derivative of q with respect to v:(8)dq(v)dv=(kt)2d2lnzdv2 .\nthe charge fluctuation will depend on the number of possible conformations of the charge and is expected to be a maximum when there are only two possible charged states to dwell . as the number of intermediate states increases , the charge fluctuation decreases .\nnow , a measure of the charge fluctuation is given by the variance of the gating charge , which can be computed from the partition function as:(9)q2=q2q2=(kt)2(zz(zz)2)=(kt)2d2lnzdv2.but the variance ( eq .\nthis implies that the slope of the q - v is maximum when there are only two states .", "answer": "the voltage dependence of charges in voltage - sensitive proteins , typically displayed as charge versus voltage ( q - v ) curves , is often quantified by fitting it to a simple two - state boltzmann function . \n this procedure overlooks the fact that the fitted parameters , including the total charge , may be incorrect if the charge is moving in multiple steps . \n we present here the derivation of a general formulation for q - v curves from multistate sequential models , including the case of infinite number of states . \n we demonstrate that the commonly used method to estimate the charge per molecule using a simple boltzmann fit is not only inadequate , but in most cases , it underestimates the moving charge times the fraction of the field .", "id": 810} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe incidence of primary cardiac tumors is low , at 0.001% to 0.03% [ 1 - 3 ] .\nthe advent of variable cardiac imaging modalities , including echocardiography and multidetector computed tomography ( ct ) , has led to the identification of an increasing number of cases of asymptomatic cardiac tumors .\ncardiac papillary fibroelastoma ( cpf ) is a rare and benign cardiac tumor that can arise anywhere in the heart , but usually involves cardiac valves .\nmoreover , the incidence of cpf in the left ventricle is lower than that in other parts of the heart .\nhere we report a case of left ventricular cpf detected by echocardiography and successfully surgically resected .\na 65-year - old woman was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle .\nprior to the referral , she was admitted to another hospital with a complaint of chest pain of 3 days ' duration . coronary angiography and echocardiography\ncoronary angiography showed no significant coronary disease , but a mass was found by echocardiography .\nshe had been treated for hypertension and a stroke she suffered 5 years prior . on physical examination , her blood pressure was 110/70 mmhg , and her pulse rate was 62 beats / min .\ntransthoracic echocardiography revealed a 1.8 1.7 cm highly mobile round mass attached by a stalk on the apical inferior wall of the left ventricle with an echolucent area ( fig .\nct of the chest showed a 1.9 1.6 cm round and pedunculated mass with soft tissue density on the apical inferior wall of the left ventricle ( fig .\non opening the left atrium , there was a mass attached deep to the inferior wall of the left ventricle .\nthe resected tumor was 1.8 1.5 cm and had the appearance of a sea anemone ( fig .\nhistology showed that the lesion had a papillary configuration with an avascular connective tissue core ( fig .\namong primary cardiac neoplasms , benign tumors account for 63% and malignant tumors for 37% .\nthe mean age at diagnosis of cpf is approximately 60 years , although it has been reported in teenagers and children .\ncpf affects both sexes , but males predominate in most series . in the study of a series at the mayo clinic from 1957 to 2001 , of 110 primary cardiac tumors that were surgically removed\na recent study reported that cpf represented 5% of primary cardiac tumors in 21 patients . in a report of 110 cpf cases ,\nabout 90% of cpfs appeared on cardiac valves , and the remainder originated from nearly all portions of the non - valvular endocardium , including the left ventricular septum , the left ventricular mural endocardium , the right ventricular outflow tract , the right atrium , the atrial septum , the papillary muscle , the chordate tendinea , the eustachian valve , and the chiari network .\nthey have a gelatinous membrane on the surface and a stalk with multiple papillary projections .\nmicroscopically , cpfs are composed of a central stalk with radiating villus - like projections .\nthe papillae are avascular structures , containing a core of dense collagen fibers admixed with varying amounts of reticulin and elastin fibers .\nthe microscopic structure of a cpf closely resembles that of chordea tendineae , which prompted some to propose a hamartomatous - like pathogenesis .\na cpf is a collection of avascular fronds of dense connective tissue lined by endothelium .\nhowever , it is deemed to be a reactive process rather than a true neoplasm .\nit is suggested that cpf may be associated with lambl 's excrescence and shear stress , and congenital factors may be involved in its development ; however , the cause remains unclear . with improved echocardiographic resolution due to higher transducers and new imaging modalities ,\ncpf was considered to be an incidental autopsy finding and to have no clinical significance in the past .\nthe clinical presentation of a cardiac tumor is determined by its location , size , and mobility .\nin particular , left - sided , larger sized ( 1 cm ) and highly mobile tumors have a higher incidence of embolization .\ncpfs have a predilection for the left side of the heart . in a review of the literature regarding complications in 79 cases of cpf\n, 61 lesions occurred on the left side of the heart , whereas only 18 were right - sided .\ncpfs are generally slow growing tumors , but may serve as nidi , allowing formation of large superimposed thrombi over a short period of time .\nsymptoms include cerebral infarction and transient cerebral ischemic attack associated with soft and fragile fibroelastoma in 44% of patients , angina pectoris in 18% , myocardial infarction in 10% , cardiac failure in 9% , and sudden death in 8% .\nsymptomatic cpf should be resected surgically ; however , there are no guidelines for the treatment of asymptomatic cpf .\nlarge , left - sided mobile tumors should be excised to prevent sudden death and emboli .\nsmall , non - mobile tumors may be followed with serial echocardiography and removed if they increase in size or become mobile or symptomatic .\nvarious methods have been proposed for complete excision of left - sided cpfs to avoid a left ventriculotomy due to further complications . for tumors deep within the left ventricular cavity close to the apex , the use of a cardioscope passing through the aortic or mitral valve is recommended to avoid damage to the valvular apparatus . in our case\n, we used a surgical approach through the left atrium and mildly pushed up the left ventricular apical inferior wall for easy resection of the mass .\nrecently , a case in which a cpf deep in the left ventricle was resected under the guidance of a gastrointestinal fiberscope was reported . in this report\n, we present a case of cpf attached to the left ventricular apical inferior wall , which was successfully removed surgically .", "answer": "cardiac papillary fibroelastoma ( cpf ) is a rare and benign primary cardiac neoplasm of unknown prevalence . \n the incidence of cpf in the left ventricle is lower than that in other parts of the heart . \n a 65-year - old female was referred to our cardiology department for evaluation of a cardiac mass of the left ventricle . \n transthoracic echocardiography revealed a 1.8 1.7 cm highly mobile round mass attached by a stalk to the apical inferior wall of the left ventricle with an echolucent area . \n the mass was successfully removed without any postoperative complications and was identified as a cpf .", "id": 811} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhepatomegaly and elevated liver enzyme levels in type 1 diabetes mellitus ( dm ) patients can be caused by hepatic glycogenosis , viral hepatitis , autoimmune hepatitis , or metabolic liver diseases .\nmauriac syndrome is a rare complication of type 1 dm that is characterized by hepatomegaly due to hepatic glycogenosis , growth retardation , delayed development of puberty , and cushingoid features .\nit is caused by abnormal hormone secretion and metabolic abnormalities because of inappropriate glycemic control1 ) .\nif the insulin dosage is insufficient to control hyperglycemia , it can stimulate hepatic glycogenosis and fatty acid synthesis , resulting in inhibition of glycogenolysis and hepatomegaly .\nhepatic glycogenosis in type 1 dm patients is a reversible complication by strict blood glucose level control , which is different from nonalcoholic steatohepatitis ( nash ) in obese type 2 dm .\nthus far , eight cases of type 1 dm accompanied by hepatic glycogenosis and three cases of mauriac syndrome have been reported in korea234 ) .\nwe report a case of hepatic glycogenosis mimicking mauriac syndrome in a patient with poorly controlled type 1 dm who showed hepatomegaly , cushingoid face , mild growth retardation , and delayed menarche .\na 14-year - old girl was admitted to the catholic university of korea , seoul st .\ntotal daily insulin dosage was 12 iu ( 0.26 iu / kg / day ) .\nshe had previously been admitted seven times because of diabetic ketoacidosis in the previous 2 years . at the time of admission , the patient had clear consciousness , with the following vital signs : blood pressure , 90/60 mmhg ; pulse , 118/min ; and body temperature , 36.5. the height of the patient was 155 cm , and her weight was 46 kg , which were in the 25th and 50th percentiles , respectively .\ngrowth velocity decreased to 3.3 cm / yr in the past 2 years ( fig .\nthe patient presented with tanner stage iv breast and tanner stage iii pubic hair ; however , the patient did not experienced menarche .\nbone age was delayed by 2 years compared to her chronological age . upon physical examination\nblood test results revealed the following values : white blood cells , 4,840/mm ( 47.5% neutrophils and 42.6% lymphocytes ) ; hemoglobin , 13.4 g / dl ; platelets , 218,000/mm ; aspartate aminotransferase ( ast ) , 1,408 iu / l ; and alanine aminotransferase ( alt ) , 459 iu / l ; gamma glutamyltransferase , 430 iu / l ; and amylase , 115 iu / l . the glycosylated hemoglobin ( hba1c ) level was 14.3% , and ketone was not detected in urine . to rule out viral hepatitis ,\nwe performed serologic tests for hepatitis a , b , and c ; epstein - barr virus ; and cytomegalovirus infections , and obtained negative results .\nfurthermore , the results of autoimmune hepatitis , including antinuclear antibody , antismooth muscle antibody , and antiliver kidney microsome antibody , were all negative .\nthyroid function was normal and the following hormone levels were presented : insulin - like growth factor-1 ( igf-1 ) , 203 ng / ml ; luteinizing hormone ( lh ) , 4.47 miu / ml ; follicle - stimulating hormone ( fsh ) , 4.77 miu / ml ; and estradiol ( e2 ) , 35.44 pg / ml . the plasma cortisol level was 5.73 g / dl and the adrenocorticotropic hormone level was 17.14 pg / ml at 8:00 am .\n3 ) . through a liver biopsy , we found ballooning degeneration with nuclear vacuolization of hepatocytes ( fig .\nhepatocytes were strongly positive in a periodic acid - schiff ( pas ) stain ( fig .\n4b ) , and such positive finding disappeared with diastase ( d - pas ) ( fig .\nthe insulin dosage was gradually increased over 3 months ; thus , the total daily insulin dosage became 36 iu ( 0.65 iu / kg / day ) .\nto prevent hypoglycemia , we prescribed 60 g ( 1.3 g / kg ) of uncooked cornstarch between meals and bedtime . after implementing strict glycemic control , hepatomegaly was improved and elevated transaminase levels returned to normal ranges .\nmoreover , the patient manifested menarche at the age of 15.3 years and a regular menstruation cycle thereafter .\nhepatic glycogenosis in type 1 dm is a key mechanism of mauriac syndrome and is a rare diabetic complication first reported by mauriac in 19305 ) .\nhepatic glycogenosis can be caused by either a persistent hyperglycemia due to insulin deficiency or conversion of excess glucose administered to control hypoglycemia due to excessive insulin administration . with regard to the latter mechanism ,\nfurthermore , the secretion of the antagonistic hormone cortisol increases in type 1 dm patients with poor glycemic control . such excess cortisol inhibits hepatic glycogenolysis and increases fatty acid synthesis in the liver , causing hepatomegaly .\nmoreover , hypercortisolism can result in cushingoid features and delay in bone maturation , which in turn leads to delayed growth and puberty1 ) .\ngrowth retardation and delayed puberty with hepatic glycogenosis in uncontrolled type 1 dm patients are distinct characteristics of mauriac syndrome . in patients with mauriac syndrome , circulating igf-1 levels are normal or reduced despite normal hypothalamic - pituitary functions .\npatients with mauriac syndrome also exhibit resistance to growth hormones , which is caused by a decrease in igf-1 bioactivity , igf-1 receptor defects , and circulating igf-1 inhibitors9101112 ) .\ndelayed puberty can manifest as a result of insulin deficiency , hyperglycemia itself , or decreased lh and fsh secretion caused by the gonadotropin - releasing hormone due to stress hormone secretion after poor glycemic control .\ninsulin administered to the subcutaneous tissue bypasses the hepatic first - pass metabolism and is absorbed directly via systemic circulation .\nthen , the insulin binds with the receptor at the ovary to excessively stimulate the ovary , thereby increasing androgen secretion .\nif peripheral insulin resistance increases because of hyperglycemia , polycystic ovary syndrome can occur , causing ovarian failure and amenorrhea1314 ) .\nalthough growth retardation and delayed puberty were not prominent in our patient , the patient exhibited very similar clinical manifestations of mauriac syndrome .\nthe reason that the signs of growth retardation and delayed puberty were mild in our patient was probably because hepatic glycogenosis occurred in the late stage of pubertal development , thereby only minimally affecting the patient 's growth and puberty . as we did not measure 24-hour urinary free cortisol levels and the 8:00 am .\nif the symptoms of mauriac syndrome recur , a detailed evaluation of hypercortisolism will be necessary\n. treatments of hepatic glycogenosis in type 1 dm include strict glycemic control through appropriate diet and insulin dosage .\nalthough regular diet and sufficient insulin dosage are important in controlling hyperglycemia , determining the appropriate insulin dosage is difficult when hyperglycemia is accompanied by frequent hypoglycemia , as in the case of our patient .\nas glycogenolysis does not properly occur even with hypoglycemia in the patient with hepatic glycogenosis , additional glucose supply is necessary .\nhowever , the glycemic effects of conventional snacks only manifest 2 hours after consumption . moreover , as the glycemic effect inevitably decreases with time , hypoglycemia can recur .\nconsequently , consuming uncooked cornstarch to induce delayed glycemic effects facilitates the prevention of hypoglycemia15 ) .\nhepatic glycogenosis does not occur in all patients with type 1 dm who have poor glycemic control .\nalthough the risk factors of hepatic glycogenosis are not yet known , we postulate that wide fluctuations of blood glucose levels and a long period of poor glycemic control increase the risk of hepatic glycogenosis .\nhowever , hepatic glycogenosis in type 1 dm is a reversible complication that is different from nash , which is often presented in obese type 2 dm patients .\ntherefore , appropriate glycemic control is important to the treatment and prevention of hepatic glycogenosis in type 1 dm .", "answer": "hepatic glycogenosis in type 1 diabetes mellitus ( dm ) can be caused by poor glycemic control due to insulin deficiency , excessive insulin treatment for diabetic ketoacidosis , or excessive glucose administration to control hypoglycemia . \n mauriac syndrome , which is characterized by hepatomegaly due to hepatic glycogenosis , growth retardation , delayed puberty , and cushingoid features , is a rare diabetic complication . \n we report a case of hepatic glycogenosis mimicking mauriac syndrome . a 14-year - old girl with poorly controlled type 1 dm \n was admitted to the catholic university of korea , seoul st . \n mary 's hospital for abdominal pain and distension . \n physical examination revealed hepatomegaly and a cushingoid face . \n the growth rate of the patient had decreased , and she had not yet experienced menarche . \n laboratory findings revealed elevated liver enzyme levels . \n a liver biopsy confirmed hepatic glycogenosis . \n continuous glucose monitoring showed hyperglycemia after meals and frequent hypoglycemia before meals . to control hyperglycemia , we increased insulin dosage by using an insulin pump . \n in addition , we prescribed uncooked cornstarch to prevent hypoglycemia . \n after strict blood glucose control , the patient 's liver functions and size normalized . \n the patient subsequently underwent menarche . \n hepatic glycogenosis is a complication of type 1 dm that is reversible with appropriate glycemic control .", "id": 812} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe anterior cruciate ligament ( acl ) is the most frequently injured knee ligament , and \n accounts for about 50% of all ligament injuries1 .\nacl injury is a common cause of knee instability and alters the \n kinematics of the knee2 .\nmost are caused by non - contact injury \n mechanisms , such as landing from a jump , or rapid deceleration3 .\nan acl injury typically occurs during the landing portion of a jump \n in ordinary sports activities and has a greater incidence among women than among men4 .\npatients with acl injury often have symptoms of knee \n instability , which may lead to functional change in and damage to other joint structures , \n and interfere with activities of daily living5 .\npatients with acl injuries have difficulty recovering normal \n walking ability and full function of the lower limbs6 .\nknee instability following acl injury results in various negative factors , which can be \n circumvented using acl reconstruction .\nreconstructive techniques have been refined to \n achieve better stabilization of the knee and other joints in order to improve functional \n recovery7 .\nit has been suggested that \n the lack of full recovery of knee function after acl reconstruction is due to sensory and \n motor behavior deficits .\nmuscle strength , endurance , flexibility and balance training are \n used as therapeutic exercises in rehabilitation settings .\nproprioceptive afferent neural \n input is also important in functional control during sports activities8 . in the clinic ,\npatients are always asked to walk normally , \n but few exercise methods provide normal proprioceptive input during walking training . in recent years ,\nrobot - assisted therapy ( rat ) rehabilitation , which simulates normal \n walking , has also been used to help patients with spinal cord injury or stroke9 .\nthe major difference between robot - assisted weight - supported treadmill training and \n existing supported ambulation training is the addition of a mechanical assistant in the rat , \n so that alternative steps with both feet can be achieved by patients10 .\nmoreover , simulation of a normal walking pattern \n facilitates input from the peripheral nerves . in this manner ,\nthe remaining central nervous \n system can be stimulated so that regeneration of the nerves involved in traumatic spinal \n cord injury can be completed .\nrecent studies have shown that this method is associated with \n significant improvements in reaction time and bowel function11 , 12 .\nthe aim of this study was to examine the long - term interventions effects of rat \n rehabilitation on functional activity levels after acl reconstruction .\nthis study recruited 8 patients who underwent arthroscopic acl reconstruction in boai \n hospitals in beijing , china , between september and december 2015 .\npatients performed \n rehabilitation exercises for at least 2 months at the department of physical therapy .\nthe \n subjects were limited to patients who had undergone acl reconstruction with autografts , \n performed by the same surgeon , and showed no differences in anatomical stability based on \n radiographic and magnetic resonance imaging .\nthe characteristics of the 8 subjects ( 6 males and 2 females ) are shown in table 1table 1.subject characteristicsmean sd ( n=8)age ( yrs)35.2 3.2height ( cm)173.4 8.6weight ( kg)79.5 16.8 . the subjects participated in rat for one month .\nthe purpose and content of \n this research were explained to the subjects , who gave their informed consent to \n participation in this study .\nthe study was approved by the research ethics committee of \n china rehabilitation research center ( irb no .\nwas carried out as traditional \n physiotherapy , which included the muscle strength training , joint mobilization , balance \n training , and endurance training .\nthe walking training used a rehabilitation training robot \n ( mbz - cpm1 , manbuzhe [ tian jin ] rehabilitation equipment co. , ltd . , china ) . in the treadmill \n and rat training ,\nthe initial training speed was 1.5 km / h , which was progressively increased \n to 1.8 km / h as quickly as possible while maintaining gait quality13 .\nthe body weight system was initiated at 35% , and 70% \n guidance force was provided for the participants14 .\nthe walking training lasted for 20 min a day , and was performed 5 \n times a week .\nthe extension strength of the knee joint , and walking and balance abilities \n were measured before and after the one - month intervention .\nwalking ability was evaluated using the 10-meter walk test ( 10mwt ) and the timed up - and - go \n ( tug ) test .\nbalance ability was assessed using the functional reach test ( frt ) . for the \n assessment of knee extension strength , surface electromyography\n( semg ) and the maximal \n extensor strength of the knee joint were measured with the subjects seated and the knee \n flexed at 45. in the semg evaluation of the vastus lateralis ( vl ) and vastus medialis ( vm ) muscles , \n maximum isometric contraction in the start position was maintained for 5 s , during which the \n maximum and average semg values of the muscle were measured by an semg system ( telemyo \n 2400 t ; noraxon , scottsdale , az , usa ) .\nthe maximum and average extensor strengths of \n isokinetic movement of the knee joint were measured using an isokinetic dynamometer ( prima \n plus , easytech , italy ) .\nthe \n wilcoxon test was used to compare the 10 mwt , tug , frt , the maximum and average semg values \n of vl and vm , and the maximum and average extensor strengths of the knee joint isokinetic \n movement before and after the one - month intervention .\nall the subjects in this study received rat training 20 times over one month . the results \n of the 8 subjects\nare shown in table \n 2table 2.the long - term interventions effects of rat10mwt ( s)tug test ( s)frt ( cm)maximum semg value of lateralis(v)average semg value of lateralis(v)maximum semg value of medialis ( v)average semg value of medialis ( v)maximum extensor strength ( nm)average extensor strength ( nm)before one month rat intervention8.8 1.1 * 10.0 0.819.3 5.1**1,872.2 966.0280.3 131.11,405 676.5189.5 60.3 * 41.0 22.3 * 37.0 21.7**after one month rat intervention7.3 0.3 * 9.5 \n1.626.5 4.8**1,915.7 827.4315.0 113.51,590 261.7230.3 67.2 * 52.3 24.1 * 47.7 22.5***p<0.05 ; * * p<0.01 .\n10mwt : 10-meter walk test ; tug : timed up - and - go ; frt : functional reach test ; rat : \n robot - assisted therapy .\n10mwt : 10-meter walk test ; tug : timed up - and - go ; frt : functional reach test ; rat : \n robot - assisted therapy the average semg value of vm , frt , and the maximum and average extensor strengths of the \n knee joint isokinetic movement increased significantly .\nhowever , the changes the maximum and average semg values of vl , the maximum \n semg values of vm and tug were not significant .\naccording to the results , the walking ability , balance ability and the extensor strength of \n the knee joint were improved by the rat treatment , and the average semg value of the vastus \n medialis muscle significantly increased .\nthe reason for these results is that robotic walking training enabled the bilateral lower \n limbs to perform alternative and circulatory movements , which can effectively adjust lower \n limb movement after acl reconstruction . in this manner , walking ability can also be \n improved .\nthere was no significant change in the semg value of the vastus lateralis , presumably \n because weakness of knee joint muscle is often observed in the vastus medialis , which is the \n first muscle to show weakness among the quadriceps muscles15 .\nmany studies have attempted to suggest the best angular velocity \n during isokinetic exercise to selectively strengthen the vastus medialis16 .\nhowever , compared to the vastus \n lateralis , the vastus medialis was clearly enhanced by rat training .\nthese results suggest that walking ability and muscle strength can be improved by robotic \n walking training as a long - term intervention .\nfuture studies with a control group and more \n subjects are needed to investigate the effects of different walking models using rat after \n long - term intervention for patients with acl reconstruction .", "answer": "[ purpose ] the aim of this study was to examine the long - term interventions effects of \n robot - assisted therapy rehabilitation on functional activity levels after anterior \n cruciate ligament reconstruction . [ subjects and methods ] the subjects were 8 patients ( 6 \n males and 2 females ) who received anterior cruciate ligament reconstruction . the subjects \n participated in robot - assisted therapy lasting for one month . \n the timed up - and - go test , \n 10-meter walk test , functional reach test , surface electromyography of the vastus \n lateralis and vastus medialis , and extensor strength of isokinetic movement of the knee \n joint were evaluated before and after the intervention . \n [ results ] the average value of the \n of vastus medialis emg , functional reach test , and the maximum and average extensor \n strength of the knee joint isokinetic movement increased significantly , and the time of \n the 10-meter walk test decreased significantly . \n [ conclusion ] these results suggest that \n walking ability and muscle strength can be improved by robotic walking training as a \n long - term intervention .", "id": 813} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncomputers now play an increasingly important role in our daily lives , and their use is \n associated with lower back pain .\nthe sacroiliac joint ( sij ) is a widely described source of \n low back pain .\ntherapeutic approaches to relieve this pain include the application of a \n pelvic compression belt ( pcb)1 . \n\nresearchers have suggested that functional exercises conducted using a pcb have a beneficial \n effect associated with muscle strengthening2 .\npcb are effective for stabilizing pelvic articulation and enable \n exercises that address coordination and stabilization3 .\nfurthermore , evidence shows that application of a pcb can relieve \n pain and facilitate neuromuscular performance during rehabilitation exercises in patients \n with lumbopelvic problems4 .\nin particular , \n pcbs effectively alter the activation patterns of hip extensor muscles in females with \n chronic low back pain during prone hip extension5 .\nmoreover , pcbs offer a conservative measure for the treatment of \n sacroiliac joint pain and are cheap and considered to be without any adverse side \n effects6 .\nin addition , it has been shown \n that use of a pcb significantly improves health - related quality of life and possibly \n decreases sacroiliac joint - related pain6 . \n\nhammer et al.7 suggested that pcb \n application is accompanied by altered rectus femoris activity when walking .\nfurthermore , pcb \n improve postural steadiness7 . however , it \n is unknown whether pcb alter trunk and lower - extremity muscle activities in healthy adults . \n\ntherefore , the purpose of this study was to investigate the effects of a pcb on these muscle \n activities in normal healthy adults .\nall \n were given comprehensive information on the study , and all provided written informed consent \n according to the ethical standards of the declaration of helsinki prior to participation and \n agreed to participate in the study ( table \n 1table 1.pre- and post - intervention electromyography values of subjects wearing or not \n wearing a pelvic compression belt ( units : % mvic)without pelvic compression beltwith pelvic compression beltchange valueerector spinae*101.7 8.8 80.9 5.6 20.8 10.9oblique internus abdominis*107.8 20.4 87.0 12.420.8 \n11.7rectus femoris*93.7 15.977.8 8.0 15.8 17.7long head of the biceps femoris*94.7 17.383.6 11.0 11.1 13.2mean sd .\ntheir average ages , heights , and weights were 21.60 1.08 years , 171.20 \n 6.23 cm , and 71.23 8.64 kg , respectively .\nsignificant intergroup difference between the gains achieved \n ( p<0.05 ) the pelvic compression belt ( the com - pressor , optp , minneapolis , mn , usa ) used was an \n adjustable body belt with four elastic compression bands that provide stabilizing pressure \n and was designed to allow the amount of compression to be adjusted at targeted compression \n sites . the pcb was placed below the anterior superior iliac spine ( asis)8 , and stabilizing pressure was applied using \n the elastic compression bands after confirming the location of the compression site .\nfour surface electromyography signals were processed \n through the mp150 system when subjects were in the bridge position and transformed into \n digital signals , which were filtered and processed using acqknowledge software ver .\n3.7.3 \n ( biopac systems inc . , goleta , ca , usa ) on a personal computer .\na 1,000 hz sampling rate was \n used for electromyography signals , and their amplified waveform was filtered using a \n 60500 hz band - pass filter and a 60 hz of notch filter . for quantifying collected signals , \n we used root mean square values9 . in \n addition , the signals collected from each muscle were normalized versus the maximal \n voluntary isometric contraction ( % mvic ) . to measure muscle activation at maximal voluntary isometric contraction ,\nafter collection of \n the data for 5 seconds at maximal voluntary isometric contraction for each muscle , the \n average electromyographic signals as a percentage of mvic for 3 of the 5 seconds , excluding \n the data for 1 second each from the beginning and end , were used .\nmuscle activation was measured using electromyogram electrodes fixed to areas of muscle \n fibers and by pressing on muscle parts and following the direction of muscle texture to find \n the appropriate positions .\nthe locations of the surface electrodes were as follows : ( 1 ) for the elector spinae , 2 cm \n lateral to the spinous process at the l45 interspace10 ; ( 2 ) for the oblique internus abdominis ( oi ) , in the center of the \n triangle formed by a horizontal line between the anterior superior iliac spine of the \n innominate and the umbilicus , midline , and the inguinal ligament11 ; ( 3 ) for the rectus femoris , the midpoint between the \n upper margin of the patella and asis12 ; \n and ( 4 ) for the long head of the biceps femoris , the midpoint between the gluteal fold and \n the knee joint13 .\nintragroup comparisons of variables before and after the intervention were performed using \n the paired samples t - test .\nibm spss statistics ver . 20.0 ( ibm corp , armonk , ny , usa )\nthe subjects showed a significant decrease in muscle activation in the erector spinae , \n oblique internus abdominis , rectus femoris , and biceps femoris while wearing the pcb \n ( p<0.05 ) ( table 1 ) .\nthis study was undertaken to determine how a pcb affects erector spinae ( es ) , oblique \n internus abdominis ( oi ) , rectus femoris ( rf ) , and long head of the biceps femoris ( bf ) \n muscle activation in healthy adults . we observed reduced es , oi , rf , and bf activity with a \n pcb compared with without a pcb in the bridge position .\nseveral possible explanations exist \n for less muscle activity in abdominal muscles than in core muscles while wearing the pcb . \n stabilizing the core is a dynamic process of maintaining balance .\nkaushik et al.14 suggested that the transverse abdominis is \n the first muscle activated during lower extremity movements , indicating that it is a primary \n muscle linked to core stability during lower limb movements . in the present study ,\nthe \n decreased oi activity indicated that subjects required less effort to maintain stability \n when wearing the pcb .\nnevertheless , kim et al.15 suggested that decreasing the activation of abdominal muscles on an \n unstable surface using an external support , such as a pcb , is suitable for improving \n abdominal muscle control and lumbopelvic stability . in a recent study by hu et al.16\n, it was found that transverse and oblique \n abdominal muscles were less active with a pcb in normal subjects because these coordinated \n muscles are activated to press the ilia against the sacrum , creating a forced closure , and \n the pelvic belt may have substituted for this stabilizing activity .\ntherefore , it is thought \n that the use of a pcb with external pelvic compression might have improved pelvic joint \n stability and altered neuromotor control of the lumbopelvic and thigh muscles .\nfirst , the small sample size may have adversely \n influenced certain variables and impacted results .\nsecond , the compression force of the \n pelvic belt was not controlled , although the belt was adjusted by a skilled physical \n therapist .\nfurthermore , we recruited healthy adults without a history of low back pain or \n sacroiliac joint pain , and thus , our findings can not be generalized to other populations . \n finally , we measured emg activity of the trunk and lower extremity , but this is insufficient \n to represent muscle force directly .\nfurther studies are needed to investigate a more diverse \n sample of normal healthy subjects .", "answer": "[ purpose ] the purpose of this study was to investigate the effects of a pelvic belt on \n the activities of trunk and lower extremity muscles in normal adults . \n [ subjects and \n methods ] the subjects were 20 normal individuals without a history of orthopedic problems . \n the pelvic compression belt ( the com - pressor , optp , minneapolis , mn , usa ) was an \n adjustable body belt with four elastic compression bands that provide stabilizing pressure \n and was designed to adjust the amount of force applied and to alter sites of compression . \n \n the body belt was placed below the anterior superior iliac spine , and stabilizing pressure \n was applied to the belt using the elastic compression bands in the bridge position after \n confirming the site of compression . \n [ results ] the subjects showed a significant decrease \n in muscle activation in the erector spinae , oblique internus abdominis , rectus femoris , \n and biceps femoris while wearing the pelvic belt . \n [ conclusion ] the use of a pelvic \n compression belt with external pelvic compression might improve pelvic joint stability and \n alter neuromotor control of the lumbopelvic and thigh muscles .", "id": 814} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na young man was referred with a chief complaint of blurred vision and pain of the left eye 1 month after herpetic encephalitis in the left frontotemporal lobe .\nthe patient had multiple foci of retinitis in the retinal periphery associated with vitritis , blot retinal hemorrhage and retinal arteriolitis .\nthe impression of acute retinal necrosis was confirmed by polymerase chain reaction of aqueous humor by detecting herpes simplex virus type 2 ; therefore , the patient received intravenous acyclovir .\nherpetic encephalitis may be a risk factor for acute retinal necrosis . the virus may reach the eye by the trans - axonal route .\nacute retinal necrosis ( arn ) is one of the clinical presentations of herpes simplex virus ( hsv ) .\nthis disease may present several years after a primary infection , or it may occur following systemic herpetic infection such as herpetic dermatitis . the prevalence of the disease is equal in both sexes and it occurs in the 5th-7th decade of life .\namerican uveitis society criteria for the diagnosis of arn syndrome are : one or more foci of retinal necrosis with discrete borders located in the peripheral retina , rapid progression in the absence of antiviral therapy , circumferential spread , occlusive vasculopathy with arteriolar involvement , prominent vitritis , and anterior chamber inflammation .\noptic neuropathy , scleritis , and pain are supportive but not required . in most patients , the diagnosis is made clinically .\npolymerase chain reaction ( pcr ) analysis of the aqueous humor can detect the cause of arn specifically .\npcr is very helpful in the detection of the varicella zoster , hsv type 1 and 2 .\npatients with arn due to hsv-1 and varicella zoster virus tend to be older , whereas those with arn due to hsv-2 tend to be younger [ 3 , 4 ] . in this article , we report one case of unilateral arn 1 month after the herpetic encephalitis .\nthe patient is a 25-year - old man who was admitted with a chief complaint of decreased vision and pain in left eye for the previous 4 days .\nthe patient also complained of perception of floating objects in the visual field of the left eye .\nthe patient had no past medical history indicating an immunocompromised state ; he had been admitted to the neurology ward due to herpetic encephalitis 1 month previous to the occurrence of visual symptoms .\nherpetic encephalitis diagnosis was made by brain mri ( fig . 1 ) and pcr analysis of the cerebrospinal fluid .\nhe did not report any underlying disease or drug consumption except oral acyclovir 800 mg every 8 h. at physical examination , the right eye was normal . in the left eye ,\nvisual acuity was 0.1 , papillary reflex was normal and marcus gunn sign was negative .\nslit lamp examination of the left eye revealed conjunctival hyperemia and ciliary injection , diffuse fine keratic precipitates in the corneal endothelium , 3 + cellular reaction in the anterior chamber , 3 + cellular reaction in the vitreous without snowball or snowbank opacities , or vitreous hemorrhage . in fundoscopic examination , multiple foci of retinitis and retinal necrosis\n2 ) associated with arteriolar involvement ( arteriolitis ) , blot retinal hemorrhage and optic disc hyperemia .\npcr analysis of aqueous humor revealed hsv-2 , so the patient was admitted with the diagnosis of arn and received intravenous acyclovir for 10 days ( 10 mg / kg / day ) .\nafter 48 h of antiviral therapy , a systemic corticosteroid ( prednisolone 1 mg / kg / day ) was introduced and subsequently tapered over several weeks to treat active inflammation .\nthe patient also received aspirin to treat an associated hypercoagulable state . with this treatment , no new lesion developed and opacity of the media decreased ; so prophylactic barrier laser photocoagulation in the areas of healthy retina at the posterior borders of the necrotic lesion prevented retinal detachment .\nintravitreal antiviral agents such as ganciclovir and foscarnet were not used in this patient because the disease was controlled by intravenous acyclovir .\nafter discharge from hospital , oral acyclovir 400 mg every 5 h was started . during follow - up ,\nthe inflammation decreased and the patient had no vitreous traction or retinal detachment or other eye involvement .\nthe brain and retinal involvement were on one side ; after 1 month of left frontotemporal lobe involvement of the brain , the retina was involved on the left side .\nsome of the studies report arn several years after neonatal and infantile herpetic encephalitis [ 5 , 6 ] ; therefore , herpetic encephalitis may be a risk factor for arn development .\nother articles report that the virus accesses the retina from the brain by the trans - axonal route ; consequently , this virus can cause recurrent episodes of arn [ 8 , 9 ] . these reports may necessitate a prophylaxis with antiviral agents after herpetic encephalitis to prevent arn . in a study by pavsio et al . , the role of long - term prophylaxis with acyclovir in children who had herpetic encephalitis is an important issue .\nprophylaxis could be considered after hsv encephalitis to prevent arn or after arn to prevent second eye involvement .\nacyclovir used as prophylaxis for recurrent genital hsv infection in adults for 5 or more years has been associated with minimal toxicity and the selection of resistant strains has not been demonstrated , but there is little experience with the duration of prophylaxis that would have been necessary to prevent arn in our patient . with this report\nwe reemphasize the correlation between these two diseases . on the other hand , arn may be an indication of possible central nervous system involvement and neuroimaging may be necessary in all cases of arn to rule out herpetic encephalitis .", "answer": "purposeto report a case of unilateral acute retinal necrosis after herpetic encephalitiscase reporta young man was referred with a chief complaint of blurred vision and pain of the left eye 1 month after herpetic encephalitis in the left frontotemporal lobe . \n the patient had multiple foci of retinitis in the retinal periphery associated with vitritis , blot retinal hemorrhage and retinal arteriolitis . \n the impression of acute retinal necrosis was confirmed by polymerase chain reaction of aqueous humor by detecting herpes simplex virus type 2 ; therefore , the patient received intravenous acyclovir.conclusionherpetic encephalitis may be a risk factor for acute retinal necrosis . \n the virus may reach the eye by the trans - axonal route . \n prophylaxis with acyclovir may be necessary after herpetic encephalitis to prevent acute retinal necrosis .", "id": 815} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe treatment of patients with multiple trauma requires a different approach to that of patients with regular trauma because they are threatened not only by the injuries themselves , but also by the metabolic disruptions that follow.1 delay in surgery , blunt trauma , extensive soft tissue damage , and combined orthopedic and vascular injuries have been associated with an increased risk of amputation , while associated nerve and bone injuries with extensive soft tissue damage are risk factors for a poor outcome.2 acute renal failure is the main cause of death in patients with war wounds and trauma of the extremities\n. it would be helpful to minimize mortality in these patients by managing shock in a timely manner and taking the decision to amputate appropriately and promptly.3 severe head injury is known to be a major determinant of mortality in patients with multiple injuries , but other injuries also contribute to the clinical outcome.4,5 different mechanisms of injury , such as motor vehicle crashes , falls , or pedestrians being struck by a motor vehicle , impart varying degrees of force and energy transfer that may impact outcomes ; this was found to predict mortality and functional impairment independently at hospital discharge.6 acute lower extremity compartment syndrome is a devastating complication that often presents silently in critically injured patients.7 patients who underwent delayed fasciotomy had twice the rate of major amputation and a three - fold higher mortality rate.8 the aim of this study was to evaluate if injuries of the extremities are associated with a higher one - month mortality rate than other types of associated trauma .\nthis prospective , observational , cohort study was carried out in the regional emergency center of hospital de base after prior approval by the ethics research committee of the so jos do rio preto medical school .\nthe emergency department follows a systematic pathway to provide initial assistance to accident victims using the atls ( advanced trauma life support ) protocol .\nall live accident victims treated in the emergency department from july 2004 to june 2005 were included .\npatients who were dead on arrival and not submitted to any type of inhospital resuscitation procedure were not included in the study .\naccident victims were allocated to two groups , ie , those with severe injuries to the extremities or pelvis ( abbreviated injury scale [ ais ] 34 ) and those without injuries or with minor injuries to the extremities ( ais 02 ) .\nthe fisher s exact test and relative risk were used for statistical analysis , and an alpha error of 5% ( p 0.05 ) was considered statistically significant .\na total of 3489 patients were evaluated in this study ; 3244 ( 92.98% ) did not have severe trauma of the extremities ( ais 02 ) , 34 ( 1.05% ) of whom died .\nsevere injuries of the extremities ( ais 34 ) occurred in 245 ( 7.02% ) of the patients , with 13 ( 5.31% ) dying ( fisher s exact test : p = 0.001 , relative risk 5.063 , 95% confidence interval [ ci ] : 2.7079.467 , table 1 ) .\ntable 2 shows the age , type of injury sustained , and time until death after trauma for the patients who died .\nof the 245 patients with ais 34 , 71 ( 28.98% ) were women and 174 ( 71.02% ) were men , with the mean age of the men being 40.1 20.5 years and of the women 60.2 23.6 years .\nthis study assessed whether severe injuries of the extremities affect the overall mortality rate in accident victims .\nthe death rate was found to be higher for patients with ais 34 than in those without injuries or with minor injuries to the limbs .\nthus , these data serve as a warning in respect to increased risk of death in orthopedic patients compared with general trauma patients . when the severity of specific injuries in accident victims is reported in the literature ,\nhead trauma is cited as one of the main causes of death.5,6 however , there are few data in the literature about the association between death and injuries to the extremities .\none study reported that the mortality rate in accident victims with extremity injuries was higher in pedestrians struck by motor vehicles ( 20% ) , and for those with head injuries , it was higher for motor cycle crash victims ( 16%).6 the first phase of management for these patients aims to control bleeding , by surgical intervention if necessary , and to prevent further wound contamination .\nthe second phase consists of resuscitation in the intensive care unit , and the third phase aims at definitive repair of the injuries sustained.9 pelvic injuries represent a thorny and stubborn therapeutic challenge .\nrapid diagnosis and effective treatment ( damage control ) of these injuries play a key role in the patient s survival , inasmuch as the mortality of multiply injured patients with pelvic ring disruption remains high ( 20%35%).10 the preclinical management of patients with multiple trauma influences the prognosis regarding mortality and morbidity .\ndiagnostic overview , protection of vital functions in the special circumstance of shock , immobilization of the spine , and treatment of isolated injuries are an essential part of preclinical management.11 the type of trauma is known to influence the mortality rate.12 in this study , all the patients received specialized pre - hospital assistance , and were treated in a regional trauma reference center . in spite of all the care given at the scene of the accident through to discharge from hospital , trauma of the extremities was a significant cause of death .\naccident victims with injuries of the extremities are at higher risk for death than those with other types of trauma .", "answer": "background : the aim of this study was to evaluate one - month hospital mortality in victims with injuries of the extremities.methods:all accident victims admitted to the hospital de base in so jos do rio preto , brazil , during the period from july 2004 to june 2005 , were evaluated in an observational study . \n patients were classified using the abbreviated injury scale ( ais ) . \n patients with severe injuries of the extremities ( ais 34 ) were compared with those without injuries or with minor extremity injuries ( ais 02).results : a total of 3489 accident victims were evaluated ; 3244 ( 92.98% ) did not suffer injuries or had minor injuries of the extremities ( ais 02 ) and 245 ( 7.02% ) had severe injuries ( ais 34 ) . \n of the 245 patients with ais 34 extremity injuries , 13 ( 5.31% ) patients died , and of those without severe injuries to the extremities , 34 ( 1.05% ) died ( fisher s exact test p = 0.0000 , relative risk 5.063 , 95% confidence interval [ ci ] : 2.7079.467).conclusion : patients with injuries of the extremities are at greater risk of death than accident victims with other types of trauma .", "id": 816} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nPreparation of Zr(Mo,W)2O8 with a larger negative thermal expansion by controlling the thermal decomposition of Zr(Mo,W)2(OH,Cl)2\u22192H2O\n\nPaper sections:\n\nThe DTA curve for ZrMo x W 2\u2212x O 7 (OH,Cl) 2 \u20222H 2 O showed the expected endothermic peak, corresponding to the weight loss and formation of the orthorhombic phase of \u03b2-ZrMo 2 O 8 , while the two exothermic peaks at 700 and 800 K can be assigned to the crystallization of the cubic \u03b3-ZrMo 2 O 8 and trigonal \u03b1\u2212ZrMo 2 O 8 phases, respectively 10 .
The solid solutions of ZrW 2\u2212x Mo x O 8 (with different values of \"x\") have been prepared by a number of scientific groups 7,8,[11][12][13][14] . A significant number of solid solutions of the precursor ZrMo x W 2\u2212x O 7 (OH) 2 \u20222H 2 O was prepared by Ling Huang and co-authors 12 . Cubic phases were obtained for x = 0.2, 0.4, 0.6, 0.7 and 0.8, but the NTE coefficients were not measured. Accurate measurement of the NTE coefficient for ZrMo x W 2\u2212x O 8 (x = 1.0) was reported in work 6 . For the cubic, ordered phase, the NTE was \u22129.0\u202210 \u22126 K \u22121 from 2 to 200 K, and \u22125. We assumed that one of the cubic-ZrMo x W 2\u2212x O 8 solutions may have a larger coefficient than that previously determined. We carefully investigated the conditions for obtaining cubic-ZrMo x W 2\u2212x O 8 (x = 0.0, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, and 2.0) from precursors and measured their NTE coefficients.
\n\nResults and Discussion\nSynthesis of the precursors and their characterization. The powders of ZrMo x W 2\u2212x O 7 (OH,Cl) 2 \u20222H 2 O were examined by powder X-ray diffraction (Fig. 1) on a DRON-RM4 diffractometer (CuK \u03b1 source, graphite monochromator at the diffracted beam, room temperature, 2\u03b8 range 5-60\u00b0). The experimental data were processed with the PowderCell program v.2.4 15 , and the data from the powder structural database powder diffraction file (PDF) were used as the reference 16 . The EDX spectral analysis was performed using a Hitachi TM3030 desktop scanning electron microscope and the Quantax70 microanalysis system.
The PXRD data showed that all the samples were single phase. We performed an EDX investigation for all the prepared samples and found that the preset stoichiometry was retained in the products of the reaction within the experimental uncertainty. Determining the content of molybdenum and tungsten in ZrMo x W 2\u2212x O 7 (OH,-Cl) 2 \u20222H 2 O by the Zen-Retgers rule is extremely difficult because of the extreme similarity of the unit cell volumes (Table 1). High-temperature experiments were carried with time-resolved diffractometry at channel 5b of the Siberian Synchrotron and Therahertz Radiation Centre 17,18 . The wavelength used was 1.516 A. The diffraction patterns were recorded by a one-coordinate detector (OD-3) developed in Budker Institute of Nuclear Physics of Siberian Branch Russian Academy of Sciences 19 . The exposure time for a frame was set to 1 minute. The samples were heated in air up to 1123 K at a rate of 10 K/min.
\n\nDTA and high-temperature PXRD of\nThe behaviours of the ZrMo x W 2\u2212x O 7 (OH,Cl) 2 \u20222H 2 O samples upon thermal decomposition are similar (Fig. 2a), but some features depend on the value of \"x\". The decomposition of ZrMo x W 2\u2212x O 7 (OH,Cl) 2 \u20222H 2 O begins at 450 K for x = 2 and increases linearly up to 500 K for x = 0. The first stage is accompanied by an endothermic effect and a weight loss (Fig. 3). The data from the high-temperature PXRD confirmed the following reaction: We calculated the molar ratio of the chloride ion to the hydroxide ion (In all the samples, the ratio was approximately 1:3.) based on the loss of the mass, which was measured by DTA, as described in article 9 . The crystallite sizes did not increase with the temperature in our experiments. Allen 20 used a long heat treatment (8 hours at 573 K) to prepare good crystalline samples of orthorhombic-ZrMo x W 2\u2212x O 8 .
The second transformation did not have a weight loss and was accompanied by an exothermal effect. The temperatures of the transformation (650-800 K) had a complex dependence on the parameter \"x\" (Fig. 2a). We observed the appearance of the peaks of a nicely crystalline cubic-phase ZrMo x W 2\u2212x O 8 in the powder pattern. The width of the synthetic \"window\" for single-phase, cubic ZrMo x W 2\u2212x O 8 was not large: 70-200 K (x = 0-1.4) and 30-50 K (x = 1.4-2.0). Preparation of pure cubic, single-phase samples required accurate work. The precursor had to be heated to the minimal possible temperature (blue line on Fig. 2b) and held for 10-60 minutes (60 minutes for x = 0 and 10 minutes for x = 2).
Further heating led to the formation of trigonal ZrMo x W 2\u2212x O 8 at 500-700 K (x = 1.2-2.0) or decomposition of the material into constituent oxides at 1050 K (x = 0-1.0) (Fig. 2b). In study 14 , it was found that the resulting products with x \u2264 0.5 would decompose to WO 3 /MoO 3 and ZrO 2 upon a temperature increase, while for x > 0.5, the cubic phase would transform into the trigonal phase. Shi Yongfang 11 noted that the appearance of the trigonal phase occurs at relatively low temperatures, i.e., 861 K (x = 0.73) and 889 K (x = 0.53). This fact was confirmed in our work. Trace amounts of the trigonal phase were often present in all the PXRD patterns, while the cubic compound was the main phase. However, we did not observe the exothermal effect for the cubic-to-trigonal transformation for x = 0.2-0.8, 1.6, and 1.8 in the DTA experiments.
Trigonal ZrMo x W 2\u2212x O 8 (x = 1.2-1.8) had a good thermal stability, and we found no evidence of its decomposition for x = 1.4, 1.6 and 1.8 under the conditions in our experiment. Trigonal ZrMo x W 2\u2212x O 8 (x = 1.2) decomposed at 1150 K. However, trigonal ZrMo 2 O 8 decayed into oxides with an exo-effect at 925 K.
We should note that all the transformations of orthorhombic-cubic-trigonal-oxides are exothermic. This can be explained if all those phases (with the exception of the oxides) are metastable in our experimental temperature ranges. The transformations were accompanied by a decrease in the volume of the formula unit (V/Z), e.g., for x = 1.2 (Fig. 4):
x 2 x 8 x 2 x 8
Our data directly indicated the formation of a poorly crystalline orthorhombic phase (Pmn2 1 ) of zirconium tungstate (ZrW 2 O 8 ) in the temperature range 550-825 K (Fig. 2).
\n\nNTE coefficient of cubic-ZrMo\nThe thermal expansion of cubic-ZrMo x W 2\u2212x O 8 was investigated using variable temperature PXRD. Diffraction data were measured using a Bruker D8 Advance diffractometer (CuK\u03b1 radiation) with a parallel-beam geometry with G\u00f6bel Mirrors. In situ experiments were carried out using an Anton Paar XRK900 reaction chamber. The patterns were measured in the 2\u03b8 range from 10 to 70\u00b0 with a step of 0.05\u00b0 and a collection time of 3 s per point. The heating rate was 12 K/min. The acquisition of the X-ray patterns was started when the given temperature was reached. Sample cooling was immediately performed. The profile analysis and structural refinement by the LeBail method were performed using the TOPAS v.4.3 program 21 , and the data from the powder structural database PDF were used as the standards 16 . The lengths of the coherent scattering domain were calculated using LVol-IB values (i.e., volume weighted mean column height based on the integral breadth).
When measuring the NTE coefficient, it is important to realize which form of cubic ZrMo x W 2\u2212x O 8 is being measured, i.e., ordered or disordered. For ZrW 2 O 8, this transition is called \u03b1 \u2192 \u03b2. In article 13 , the thermal effects for the transition (ordered \u2192 disordered) were measured, and a formula describing the temperature of the \u03b1 \u2192 \u03b2 transitions for cubic-ZrMo x W 2\u2212x O 8 was proposed: T (K) = 432-168.45\u2022x. We used it in our work to estimate whether the NTE coefficient belongs to the corresponding ordered or disordered form (Table 2). Of course, the dependence is not linear for x > 1; this is clearly visible when comparing the calculated and experimental values for x = 1.8 and 2.0 (Table 2).
We were able to obtain reliable data for the NTE coefficients for only the disordered phase, except for x = 1.8. The calculated coefficients have similar values (from \u22123.5\u202210 \u22126 K \u22121 to \u22124.5\u202210 \u22126 K \u22121 ) and almost did not differ from those of the \"pure components\". Our value of the NTE coefficient, 3.5\u202210 \u22126 K \u22121 , for x = 0.4 did not coincide with the value 8 Heating of the precursors up to T = 525-50\u2022x K affords crystals of orthorhombic ZrMo x W 2\u2212x O 8 (10-15 nm). Cubic ZrMo x W 2\u2212x O 8 solid solutions with a small crystal grain size (30-100 nm) can be obtained by thermal decomposition of the corresponding precursor or orthorhombic ZrMo x W 2\u2212x O 8 at a temperature up to 850-900 K at x \u2264 1.8 and T = 2200-750\u2022x K at x > 1.8.
Trigonal ZrMo x W 2\u2212x O 8 (only for x > 1) can be prepared by heating the precursor or cubic ZrMo x W 2\u2212x O 8 or orthorhombic ZrMo x W 2\u2212x O 8 up to 850-1050 K, depending on the exact composition.
Solid solutions of cubic ZrMo x W 2\u2212x O 8 in the ordered form have a higher coefficient of thermal expansion (CTE) in comparison to that of other materials, but they exist in a very limited and relatively low-temperature range, which limits their possible applications.
The disordered form of cubic ZrMo x W 2\u2212x O 8 solid solutions does not have an advantage over that of the \"pure components\" in the value of CTE. The use of solid solutions is justified in the case when it is necessary to have a uniform CTE material for a certain temperature range (e.g., 250-800 K for x = 1.0).
", "answer": "Solid solutions of Zr(Mo,W) 2 O 7 (OH,Cl) 2 \u20222H 2 O with a preset ratio of components were prepared by a hydrothermal method. The chemical composition of the solutions was determined by energy dispersive X-ray spectroscopy (EDX). For all the samples of ZrMo x W 2\u2212x O 7 (OH,Cl) 2 \u20222H 2 O (x = 0.0, 0.2,", "id": 817} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nosteosarcoma ( os ) develops most frequently in the extremities , and it is the most common histologic form of the primary bone cancers.1 \n 2 head and neck oss are rare , comprising only 6 to 10% of all oss.3 \n\n4 they typically present in the third or fourth decade of life and comprise only 1% of all pediatric head and neck malignancies .\nthe most common craniofacial sites affected by oss are the mandible and maxilla , followed by the calvaria and then the skull base.4 \n 5 \n 6 on cytology , os can be divided into several pathologic types , including the pleomorphic , epithelioid , chondroblastic , small cell , mixed , and osteoclast - like giant cell types.6 in head and neck oss , the chondroblastic type occurs most frequently.7 \n skull base oss can be challenging to resect and an aggressive surgical approach can result in poor cosmetic outcome.8 imaging plays a crucial role in the diagnosis of each subtype of os and ultimately in patients ' survival because the diagnosis is based on a combination of histopathologic and imaging features .\nthe therapeutic options and prognoses for different types of os differ from each other , so correct diagnosis is essential.9 \n 10 magnetic resonance imaging ( mri ) or computed tomographic ( ct ) scan should be used to assess the extent of the primary tumor.11 \n in this case report , we describe a pediatric patient of occipital os of the chondroblastic type .\nthe chondroblastic type of os has an exceedingly poor outcome.12 however , the detailed imaging description of such cases have not been reported in the previous literatures .\nwe present the ct , mri , and enhanced mri features of this case , followed by a brief review of the related cases reported in the previous literatures\na 9-year - old boy was admitted to our hospital with a major complaint of a growing mass on his head .\nphysical examination found a firm and tough mass on the right occipital that showed no tenderness upon palpation .\nct scan showed the right occipital bone to be irregularly thickened with fluffy and cloudy calcification , with a mass deriving from the internal occipital protuberance extending toward the basilar part of the occipital bone , invading the neighboring jugular foramen , the sublingual neural tube , and the mamillary process . on mri ,\nthe lesion was 4.5- 5.5- 6.5-cm in size with calcifications areas of hypointensity in t1- and heterogeneous in t2-weighted series .\ncontrast mri showed peripheral and septal enhancement in the interior side of the tumor ( fig .\nsignificant mass effect was present , distorting the cerebellar hemisphere , pons , and the forth ventricle , which led to hydrocephalus , and the oppression of the sigmoid sinus and the transverse sinus .\n2 ) , corresponding to the features of chondroblastic os , and occipital bone chondroblastic os was the final definitive diagnosis .\n( b ) t1-weighted image shows a 4- 8- 10-cm mass lesion , isointense to the skull .\n( c , d ) the mass is hypointense in most areas in the t2-weighted series , with focal high signals in the t2-weighted series and reduced signal in flair series.(e ) in gd - enhanced mri , most areas show no enhancement or heterogeneous enhancement , with peripheral and atypical septal enhancement on the coronal plane ( white arrows ) .\n( f ) no hyperintensity was observed in both intra- and peritumoral areas in the dwi series . \n\nhistopathologic examination ( hematoxylin and eosin , 200 ) shows lace - like osteoid material abutting the neoplastic cells .\nthey typically present in the third or fourth decade of life , account for fewer than 5% of oss in children , and comprise only 1% of all pediatric head and neck malignancies .\nthe most common craniofacial sites are the mandible and maxilla , followed by the calvaria and then the skull base.13 \n 14 \n 15 our case in the right occipital bone of skull base is a very rare location . a search of the english language literature revealed 22 cranial oss previously reported in children ( table 1 ) : 12 calvarial tumors and 10 tumors of the skull base .\nthe mean age of the pediatric patients with cranial os was 12.2 years old in this table .\ncan be divided into pleomorphic , epithelioid , chondroblastic , small cell , mixed , and osteoclast - like giant cell types.6 our case is a chondroblastic subtype , which occurs most frequently in head and neck oss .\nabbreviations : gtr , gross total resection ; nr , not reported ; rt , radiation therapy ; str , subtotal resection .\nthe etiology of os is unknown , but the major risk factors for development of os in craniofacial bones may be similar to those of the long skeletal bones , consisting of exposure to radiation , retinoblastoma , li - fraumeni syndrome , and paget 's disease .\nother bone abnormalities , such as fibrous dysplasia , multiple osteochondromatosis , chronic osteomyelitis , myositis ossificans , and trauma , have also been proposed as risk factors.7 \n 15 \n 16 the presenting symptoms varied with the location of the tumors .\nthe maxillary or cranial lesions usually produced no pain , which was in accordance with our case ; however , mandibular tumors frequently presented with focal painful swelling.17 \n 18 other common presenting symptoms include headache , cranial nerve palsies , exophthalmos , and visual impairment due to different location of the tumor.5 \n 13 \n ct best demonstrates tumor mineralization , especially when minimal , and it is usually able to demonstrate tumor extension into the soft tissues . hemorrhage , necrosis , and unmineralized , chondroblastic , or fibroblastic components of the tumor will appear as areas of low attenuation on ct if present . unlike any other conventional oss , we see fluffy calcification in our case , and we believe it is a characteristic of os . the osteoblastic subtype is most common with nearly 90% containing variable amounts of cloudlike opacities.19 bose20 reported an osteoblastic os that appears as a large soft tissue density mass with a few bony densities .\ncompared with our case , the soft tissue mass is prominent and the calcification is less and diffuse .\nmri is the preferred modality for locally staging os , and it should be performed before percutaneous biopsy because it can help identify areas of viable tumor and mineralized matrix . in our case of gadolinium ( gd)enhanced mri\n, we found no enhancement or heterogeneous enhancement in most areas of the tumor , with septonodular and rim enhancement , which is in in accordance with the current literature .\nareas that demonstrate either a heterogeneous enhancement pattern or lack enhancement are the preferred sites for biopsy because they are more likely to contain both chondroid and osteoid elements that are necessary for the correct diagnosis.21 \n 22 chondrosarcomas shows similar image characteristic , but they occur in an older age with a mean age of 57 years old .\nchondroblastic oss also have significantly higher minimum and maximum apparent diffusion coefficient ( adc ) values compared with other conventional os subtypes , but they have a lower minimum adc and similar maximum adc value compared with chondrosarcoma.23 \n skull base oss can be challenging to resect , and an aggressive surgical approach can result in poor cosmetic outcome .\nthus , skull base tumors have a poorer prognosis than mandibular or maxillary tumors.3 complete surgical excision is the mainstay of treatment of the primary tumor .\nlocal recurrence is the main reason of treatment failure and mortality in head and neck oss .\npositive margins and a high tumor grade correlate with a statistically significant decrease in survival.11 in our case , the tumor could not be completely removed because it invades significant neighboring bone structures , including the jugular foreman and the sublingual neural tube .\nthe patient died after 6 months as a result of local recurrence . in summary ,\nchondroblastic os has been shown to be associated with a poor preoperative chemotherapy response and has a worse prognosis than other variants.24 however , this subtype has some particular image characteristic , which helps surgeons identify before surgery and set early therapeutic regimens .", "answer": "primary osteosarcomas of the skull and skull base are rare and comprise < 2% of all skull tumors . in head and neck osteosarcomas , \n the chondroblastic subtype occurs most frequently , which has an exceedingly poor outcome , but its image characteristic remains unknown . \n herein , we report a case in the right occipital bone of the skull base and the unique characteristics of image . pathologic examination of the surgical specimens led to the diagnosis of chondroblastic osteosarcomas . \n we believe those image characteristics can improve the understanding of skull chondroblastic osteosarcoma and the preoperative diagnosis .", "id": 818} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrecent results from the national institutes of health ( nih ) frequent hemodialysis network ( fhn ) daily trial and the following rehabilitation , economics and everyday - dialysis outcome measurements ( freedom ) study have provided confirmation of the clinical and quality of life ( qol ) benefits of short daily hemodialysis ( sdhd ) when compared to conventional thrice weekly in - center hemodialysis ( chd ) .\nthe fhn study was conducted in - center ; however , sdhd in the usa is more commonly performed as a home therapy and is not offered as a standard treatment modality in most dialysis clinics .\nalthough it has been nearly 50 years since the early pioneers such as belding scribner and stanley shaldon began dialyzing patients in their homes , peaking at 40% of all us dialysis patients in 1973 , the popularity of home hemodialysis ( hd ) has been limited in the usa for a number of reasons , including lack of suitable equipment and increased cost .\nthe last few years , however , have seen a revival in home hd , resulting in renewed interest in the various forms of more frequent therapy , including sdhd .\nthe revival of home dialysis was led in the mid 1990s by robert uldall , andreas pierratos and others in canada , gradually spreading throughout the usa .\nthis re - emergence has been made possible by recent advances in technology , including portable and more user - friendly machines designed specifically for use in the home environment . in 2005 , the fda cleared the first hd machine for home use in the usa , the nxstage system one. fda clearance was based on an open - label , prospective , two - treatment two - period crossover study on 32 patients to compare sdhd performed in - center ( prescribed six times / week ) versus sdhd performed at home .\nthe study was conducted at six centers in the usa under an investigational device exemption .\nthis study showed sdhd was delivered as efficiently in the home environment as in - center , with 98.5% of treatments performed successfully in - center versus 97.3% at home .\nnotably , the composite rate of intra - dialytic and inter - dialytic adverse events was significantly higher during the in - center phase when compared with the home phase ( 5.3 versus 2.1 adverse events/100 treatments ; p = 0.007 ) , suggesting hd therapy is at least as safe at home as in - center .\nwhen comparing clinical parameters from the period immediately preceding the study when patients were treated with conventional thrice weekly center hd , home sdhd was associated with reductions in blood pressure , antihypertensive medications and interdialytic weight gain . since the clearance of the nxstage system one in the usa , the number of patients now performing home dialysis is estimated to be 5000 , with the majority of these patients performing sdhd .\nalthough this represents a considerable increase over the past 5 years , it is still only 1% of the total end - stage renal disease ( esrd ) population .\nsdhd offers the promise of improved clinical outcomes in patients with kidney failure , and given the positive results recently released from both the fhn and freedom studies outlined below , sdhd has the potential to become a more viable and popular choice amongst many esrd patients .\nresults recently published from the fhn daily trial , funded by the nih , showed that in - center sdhd ( prescribed six times / week ) , provided significant benefits in both composite co - primary outcomes of death or 12-month change in left ventricular mass ( lvm ) and death or 12-month change in the rand-36 physical health composite ( phc ) score .\nspecifically , the fhn daily trial showed patients randomized to sdhd reduced their lvm by 16.3 35.3 g ( p < 0.001 ) and improved their phc score by 3.3 8.9 points ( p = 0.004 ) , after 12 months .\nhowever , patients on sdhd were more likely to undergo interventions related to vascular access , a result which will require further elucidation with the ongoing analysis of the trial\n. the fhn trial will be a tremendous source of data to further dissect the advantages seen with daily therapy in the coming years .\nthe freedom study is an ongoing prospective cohort study investigating the clinical and economic benefits of sdhd .\nthe objectives of the freedom study are to compare a cohort of patients starting sdhd using the nxstage system one to a matched cohort of patients receiving chd for all - cause hospitalizations and non - treatment - related medical expenditures .\nusing a 10-to-1 ratio , totaling 5000 patients , the matched thrice weekly in - center hd cohort will be obtained from the us renal data system ( usrds ) database .\nin addition , changes in qol measures , urea kinetics , management of anemia , bone and mineral metabolism , nutrition , vascular access interventions and use of medications will be examined .\nthe freedom study will involve up to 70 clinical sites and 500 participants , with a minimum 1-year follow - up .\nstudy participants complete qol surveys at the time of study enrollment , at 4 and 12 months and every 6 months thereafter .\ninterim data recently released from the freedom study has shown that sdhd , performed in the home environment , is associated with significant improvements in several important clinical and qol measures when compared to conventional thrice weekly in - center hd .\ninterim results from the freedom study investigating the effect of sdhd on depressive symptoms were recently published .\ndepressive symptoms were examined in 248 participants at enrollment and at 4 and 12 months by administering the validated beck depression inventory ( bdi)-ii survey .\nthe study protocol requires that the site investigator be notified immediately of a bdi score > 10 , with mild and moderate to severe depressive symptoms defined as bdi scores of 1115 and > 15 , respectively . in summary ,\nsdhd was associated with a significant improvement in mean bdi score over 12 months [ 11.2 , 95% confidence interval ( ci ) 9.612.9 , versus 7.8 ( 95% ci 6.59.1 ) ; p < 0.001 ] , in the per - protocol ( pp ) cohort .\nsimilar results were found in the intent - to - treat ( itt ) cohort . for participants with moderate to severe depressive symptoms , the bdi scores almost halved over 12 months [ 24.4 ( 95% ci 19.429.4 ) versus 12.6 ( 95% ci 8.017.2 ) ; p < 0.001 ] .\nit should be noted that a bdi score > 15 previously has been shown to be highly predictive of a diagnosis of clinical depression .\nthe percentage of participants with depressive symptoms ( bdi score > 10 ) significantly decreased during 12 months ( 41 versus 27% ; p < 0.03 ) . similarly in the fhn study , patients participating in the daily arm did show a trend toward improvement after 12 months when compared to baseline ( 12.6 8.7 versus 10.4 8.5 , p = 0.1 ) .\nalthough this trend was not statistically significant , one might speculate that undergoing daily dialysis therapy at home may contribute to this improvement .\nconsidering the practical feasibility of daily dialysis both from a logistical and a patient comfort perspective , one might hypothesize that the home setting may further enhance the benefits of sdhd experienced in - center .\nthe long - term effect of sdhd on post - dialysis recovery time was also assessed in the freedom study by administering the following previously validated question : how long does it take you to recover from a dialysis session and resume your normal , usual activities? interim results were recently published and confirmed that sdhd is associated with a significant decrease in post - dialysis recovery time [ 476 min ( 95% ci 359594 ) versus 63 min ( 95% ci 3295 ) ; p < 0.001 ] .\nthe percentage of participants experiencing prolonged post - dialysis recovery time ( > 60 min ) also significantly decreased over the 12-month period ( 81 versus 35% ; p < 0.001 ) .\nthe fhn daily trial showed significant improvements in control of hyperphosphatemia for patients on sdhd .\na significant reduction in mean serum phosphate was also reported in an interim report from the freedom study , along with significant reductions in the calcium phosphate product , serum creatinine , serum potassium and a trend toward a reduction in blood urea nitrogen .\nboth the fhn daily trial and an interim analysis from the freedom study showed no change in serum albumin levels .\nwell - known uremic symptoms , including restless legs symptoms ( rls ) and poor sleep quality are common in the hd population .\npoor sleep quality and rls have both been linked to increased risk of death for these patients [ 9 , 10 ] .\na recent interim report from the freedom study demonstrated initiation of sdhd at home is associated with significant improvement in rls and sleep disturbances .\nresults from 235 patients found 40% suffered from rls at baseline , which was associated with poorer sleep quality and respiratory disturbances . among patients with rls , the mean irls ( international restless legs severity scale ) score improved significantly at month 12 , after adjustment for use of rls - related medications ( 18 versus 11 , p < 0.0001 ) . among patients with moderate - to - severe rls ( irls score 15 )\n, there was an even greater improvement in the irls score ( 23 versus 13 , p < 0.001 ) . over the 12-month period , there was decline in the percentage of patients reporting rls ( 35 versus 26% , p = 0.05 ) and those reporting moderate - to - severe restless legs symptoms ( 59 versus 43% , p = 0.06 ) .\nthere was a similar and sustained improvement in several scales of the medical outcomes study sleep survey over 12 months , after adjustment for presence of rls and use of anxiolytics and hypnotics .\nrecent results from both the fhn daily trial and freedom study have shown that sdhd , performed either in - center or at home , is associated with several important clinical and qol benefits when compared to conventional thrice weekly hd .\nthe improvements in left ventricular mass , control of hypertension and improvement in hyperphosphatemia demonstrated in the fhn trial , in conjunction with the positive interim findings from the freedom study , including improvements in depressive symptoms , post - dialysis fatigue , various laboratory parameters , restless leg syndrome and sleep disorders , confirm the anecdotal benefits of sdhd seen and reported by many practicing nephrologists and their patients . until now\n, a complex variety of reasons has hindered the more widespread use of sdhd in the usa and globally .\nhowever , the results of these studies may provide a new impetus for esrd patients and nephrologists to reconsider the paradigm of thrice weekly center hd as the default therapy. such a paradigm shift will likely increase the possibility for improved clinical outcomes and overall patient care for those affected by esrd .", "answer": "thrice weekly in - center hemodialysis is the standard of care for dialysis patients with end - stage renal disease ( esrd ) . however , there is ongoing debate as to whether more frequent hemodialysis , with its readier management of both toxin and fluid removal , benefits patients . \n new evidence from recent studies , both in center dialysis and in home haemodialysis patients , adds further confirmation of improved cardiovascular outcome and quality of life in patients undergoing short daily hemodialysis . \n a paradigm shift in esrd care delivery may be facilitated due to new technology enabling daily therapy at home .", "id": 819} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nNickel(II) Dithiocarbamate Complexes Containing Sulforhodamine B as Fluorescent Probes for Selective Detection of Nitrogen Dioxide\n\nPaper sections:\n\nAs a dominant component in the NOx (x = 1 or 2) family, nitrogen dioxide (NO2) is a major air pollutant generated from high temperature oxidation of molecular nitrogen by oxygen in combustion.1 Whereas biologically, nitrogen dioxide is implicated as the root cause of toxic effects of reactive nitrogen species derived from nitric oxide oxidation by oxygen in the cellular system2 and from one-electron reduction of nitrite by metalloenzymes.3 As an air stable and strong lipophilic oxidant, nitrogen dioxide can trigger lipid auto-oxidation4 and oxidative nitration of aromatic amino acids, particularly tyrosine.5 However, there is a lack of selective fluorescent probes for convenient detection of nitrogen dioxide. Most fluorescent probes reported are for nitric oxide (NO) detection. While transition metal complex based probes contain the nitric oxide reactive metal as fluorescence quencher,6-10 the organic dye based probes detect nitric oxide indirectly through oxidation of aromatic amines by N2O3,11-12, which is produced via oxidation of NO by O2.13-14 We herein report the first fluorescent probe for selective detection of nitrogen dioxide, containing Ni(II) as a fluorescence quencher and NO2 reaction center.
Reaction of sulforhodamine with oxalyl chloride yielded a mixture of two isomeric compounds with -SO2Cl group in para or ortho position of the phenyl ring.15 The mixture was treated directly with piperazine and two isomers produced were separated readily by column chromatography to give para isomer, 1 and ortho isomer, 2 (Scheme 1). Due to their similarity, it was difficult to unambiguously distinguish their structures based on NMR and MS spectra alone. Hence the structures of the isomers were determined by single crystal X-ray diffractions (Figure S1) and, accordingly, the 1H NMR spectral data was assigned with certainty. In the presence of sodium hydroxide, the two isomers reacted readily with carbon disulfide to produce dithiocarbamate sodium salts 3 and 4, respectively. Dithiocarbamate is a bidentate ligand that promptly forms complexes with many transition metals, leading to quenching of the ligand fluorescence. It is reported that Ni(II) bisdithiocarbamate complexes, Ni(II)(RNCS2)2, reacts immediately with nitrogen dioxide to yield the oxidative dimerized ligand, (RNCS2)2,16 which could be fluorescent if R is a fluorophore. Hence, in order to prepare a Ni(II) based turn-on fluorescent probe for nitrogen dioxide, we mixed nickel(II) nitrate with 3 and 4 at 1 to 2 ratio and prepared 5 and 6 (Scheme 1). The structures of 5 and 6 were characterized by 1H NMR and the results were in agreement with a diamagnetic nickel complex with square-planar configuration. Additionally, their MALDI-TOF mass spectra showed isotope distribution pattern matching the expected molecular formula (Figure S2).
To illustrate the effect of two isomers on fluorescence quenching, the fluorescence quantum yields of compounds shown in Scheme 1 were measured (Table S1). The presence of piperazine group at ortho position (2, QY = 0.21) has reduced the quantum yield of the parent compound (sulforhodamine B, QY = 0.34) more significantly than the para isomer (1, QY = 0.28). Dithiocarbamate groups further reduced the quantum yield a little bit. The ortho isomer of the Ni(II) complex has the lowest quantum yield, and is 70 times lower than the ligand itself, while the para isomer 5 has only five times lower quantum yield comparing to 3. Energy transfer is not likely due to the small absorbance bands overlap between fluorophore emission and quencher absorption (Figure S3).
The mechanism behind fluorescence quenching is probably attributed to photo-induced electron transfer (PeT) from electron donor Ni(II) to sulforhodamine B excited state. The HOMO and LUMO energies of Ni(Me2NCS2)2 was calculated to be \u22124.09 and \u22121.03 eV respectively and dithiocarbamate ligand is known to stabilize Ni(III).17 Whereas the HOMO and LUMO of rhodamine B was \u22128.058 and \u22125.266 eV respectively.18 Therefore, PeT from Ni to rhoamdine B chromophore is energetically favored. PeT is highly sensitive to the distance between the fluorophore and the quencher; therefore, the shorter distance of Ni to the center of the fluorophore in 6 is likely to cause a much higher quenching efficiency than 5. From the crystal structures of 1 and 2, the distances of nitrogen (NH) in piperazine group to the centers of the fluorophore were calculated to be 9.4 and 7.4 \u00c5, respectively. Although we failed to obtain single crystal structures of the Ni complexes, it is reasonable to assume that the distance of the Ni to the rhodamine B chromophore would be shorter in 6 in comparison to that in 5. It should be born in mind that in solution, molecular motions will have significant effect on the distances.
We evaluated the selectivity of the ortho isomer 6 towards common reactive oxygen species (ROS) in methanol (Figure S5). Only NO2 could increase the fluorescence intensity by more than 12 times, whereas other biological relevant ROS could not do so. Neither nitrite nor nitrate could switch on the fluorescence. Moreover, addition of nitric oxide donor diethylamine NONOate (DEANO) rapidly turned on the fluorescence by 12 fold within minutes and there was excellent dose response between the fluorescence intensity and the DEANO concentrations (Figure S7). In comparison, when para isomer 5 is used, the magnitude of fluorescence increase is only 1.9 times (Figure S6). Although there is a sulfonate group on the fluorophore of probe 6, its water solubility is extremely poor. In aqueous media (water and buffer), there was no fluorescence intensity gain after addition of NO2. It turned out that the reaction products precipitated out even at micromolar concentration level used in the experiment. Addition of surfactant (Tween 20) to the reaction mixture before adding NO2 led to fluorescence turning on. Therefore, to introduce the probe into physiological condition, we applied DOTAP (1,2-dioleoyl-3-trimethylammonium-propane chloride salt) liposome as a delivery vehicle for our probe. It is found that probe 6 delivered by DOTAP demonstrated excellent selectivity to NO2 (Figure 1) and good dose-response to DEANO (Figure 2) in buffered aqueous media to simulate the physiological conditions.
To further test whether the probe is sensitive to nitric oxide or nitrogen dioxide, we carried out the reaction in the absence of oxygen by degassing the probe solutions and DEANO solutions before mixing them under nitrogen, and we failed to observe any fluorescence turning-on event. This observation showed that the fluorescence turning-on by DEANO required oxygen, suggesting that it is NO2 that reacts with the probe as NO generated from DEANO is rapidly oxidized to NO2 by oxygen present in the solution.19 This was confirmed by a separate test in which the response of the probe to NO2 gas formed by mixing NO and air or commercial NO2 gas was examined. Indeed, fluorescence was turned on. To further verify if the reaction products of 6 with DEANO in the presence of air and with NO2 gas are identical, the reaction products were analyzed using HPLC and LC-MS. The results suggested that the same major products with fluorescence were generated by the probe reacted with DEANO in the presence of air and with NO2 gas in methanol. These results clearly show that NO2 can turn on the fluorescence of the probe. Moreover, the para isomer 5 also reacted with NO2 in the same way as the ortho isomer 6, as characterized by HPLC chromatograms (Figure 3).
The structures of the reaction products were then deduced on the basis of LC-MSn spectra and shown in Scheme 2. Apparently, NO2 brought forth the oxidation of dithiocarbamate ligand and generated Ni(II) free compounds with high fluorescence. We proposed that the reaction is initiated by NO2 adduct with 5/6, forming Ni(III)(R2NCS2)2(NO2). Subsequent intramolecular electron transfer reaction forms Ni(II) complex and R2NCS2\u2022 radical, which couples to give ligand dimer shown in peak B/B' (Scheme 2). The compound shown in peak A/A' is generated due to secondary oxidation reaction of (R2NCS2)2 followed by methanolysis. Consistent with the two proposed compounds, ESI-MS results of the compound shown in peak A/A' gave [M+H]+ peak at m/z = 749.2 and [M+Na]+ peak at m/z = 771.2, while ESI-MS results of compound for B/B' demonstrated two dications, [M+2H]2+ at m/z = 702.2 and [M+2Na]2+ at m/z = 724.2, respectively. Our assignments are supported by ESI-MS2 fragmentation patterns of A\u02ca/B\u02ca. MS2 spectrum of peak A' shown three fragments at 717.1 ((M + H)+ \u2013 CH3OH), 669.2 ((M + H)+ \u2013 SO3), and 637.0 ((M + H)+ \u2013 CH3OH \u2013 SO3), respectively. MS2 spectrum of B' gave a peak at m/z = 627.2 formed from the molecular cation through homolytic cleavage of the S-S bond followed by losing a CS2 (Figure S4).
In addition, the formula of A' and B' were confirmed by high resolution MS spectra (Table S2). Our results are in agreement with literature work, which showed that bis(diethyldithiocarbamatonickel(II)) (Ni(dtc)2) reacted with NO2, but not with NO, to give corresponding paramagnetic Ni(III)(dtc)3 as an intermediate, which decomposed to oxidized dithiocarbamate ligand, i.e. thiuram disulfide ((R2NCS2)2).16
Considering the high toxicity of NO2 in atmosphere, Health and Safety Commission (HSC) of USA has approved Occupational Exposure Standards (OESs) of 1 ppm (8-hour time weighted average) and 5 ppm (short-term exposure limit) for NO2.20 Convenient detection of gaseous NO2 would be ideal for monitoring air pollution due to NOx (x = 1 or 2, with NO2 being dominant species). For this purpose, probe 6 was successfully applied in visual detection of gaseous NO2 with the detection limit reaching 1.0 ppm using NO2 indicator strips prepared by dropping methanol/chloroform (1:1) solution of 6 (800 nM) on filter paper to give round stains of ca. 5 mm in diameter after solvent evaporation. The NO2 indicator strips were exposed to different concentrations of NO2 gas for 10 minutes. Under regular laboratory lighting conditions, there was no apparent spot detected for all indicator strips (Figure 4 right). When the strips were exposed to UV lamp (352 nm), red fluorescence spots could be observed visually for strips exposed to NO2 gas at concentration as low as 1.0 ppm and the fluorescence intensity increased in a dose dependent manner at 10 and 100 ppm NO2 (Figure 4 left). The results demonstrated that this NO2 indicator strips immobilized with probe 6 is a simple, direct and economical tool for rapid detection of gaseous NO2 at low concentrations.
To introduce the probe into biological system, liposomal carrier was applied. Cationic liposomes have been studied extensively in gene therapy applications and also cationic lipids are effective in vaccine formulations to treat cancers.21-22 Therefore, we applied DOTAP liposome as a delivery vehicle for our probe. Although it is known that DOTAP liposome at high concentration is toxic to cells, our observation showed that RAW 264.7 cells can withstand up to 100 \u03bcM DOTAP (Figure S8). To illustrate that the probe 6 uptaken by cells can be turned on by adding NO2, the RAW 264.7 cells treated with DOTAP liposome containing 6 (5 \u03bcM) were further treated with DEANO as a NO2 donor.19 The fluorescence images of the cells (Figure 5B, D) clearly illustrate that fluorescence intensity could be efficiently enhanced by adding DEANO (for intensity plot please refer to Figure S9). Moreover, the Z-stack gallery image (Figure S10) clearly shows that RAW 264.7 cells were able to efficiently uptake the probe 6 dispersed in DOTAP. A 3D image (Figure 5A, B, C, D) was also given to demonstrate the depth distribution of probe 6 inside cells, both treated and not treated with DEANO.
In conclusion, we have demonstrated that dithiocarbamate Ni(II) complexes containing sulforhodamine B fluorophore is a highly selective probe for detection of nitrogen dioxide. To the best of our knowledge, this is the first example of live cell fluorescence imaging of NO2 activity and visual detection of gaseous NO2 at low concentrations. Many third row transition metals are good fluorescence quenchers because their complexes with fluorescent ligands are paramagnetic due to the unpaired metal d electrons. In contrast, Ni(II) coordination sphere in complex 5 and 6 adopt square planar geometry and are diamagnetic. It warrants further research on understanding the quenching mechanisms of Ni(II) and developing even more sensitive probes with rationale combination of fluorophore and nickel complex.
", "answer": "We synthesized the Ni(II) complexes with dithiocarbamate ligand derived from ortho and para isomers sulforhodamine B fluorophores and demonstrated they are highly selective in reaction with nitrogen dioxide (NO2). Comparing to the para isomer, the ortho isomer showed much greater fluorescence increase upon reaction with nitrogen dioxide, which led to oxidation and de-complexation of dithiocarbamate ligand from Ni(II). We applied this probe for visual detection of 1 ppm nitrogen dioxide in gas phase and fluorescence imaging of NO2 in macrophage cells treated with nitrogen oxide donor.", "id": 820} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnumerous causes have been attributed to low back pain ( lbp ) . a long list exists , but the enlistment of sacralization as one of the causes has resulted in a lot of controversy .\nsacralization is a congenital vertebral anomaly of the lumbosacral spine ( fusion between l5 and the first sacral segment ) .\nseveral studies have described the occurrence of this anomaly in a back pain population [ 27 ] .\nsome authors have stated that sacralization is incidentally diagnosed and has no clinical impact [ 7 , 8 ] , whereas others claim that this anomaly may predispose patients to certain clinical disorders [ 911 ] .\nthis controversy has been quite intriguing and has been the stimulus for carrying out this present study .\nthe intention was to examine in detail the incidence of this anomaly in the lbp population .\nour study aimed to use the incidence of this congenital anomaly to establish a relationship between it and lbp .\nafter institution review board approval for this prospective study , 500 lumbosacral radiographs of lbp patients and 500 radiographs of control group were collected over a one - year period .\nthe ages ranged between 16 years and 73 years , and both sexes were involved .\nexclusion criteria consisted of any radiologic evidence of previous lumbosacral surgery that would obstruct our measurements . a total of 1000 lumbosacral films were examined and identified as being adequate for measurement of the desired parameters .\ndata collection consisted of the subject 's age at the time of imaging , gender , number of lumbar vertebral bodies , and bilateral height measurement of the lowest lumbar transverse process .\nthree orthopedic spine fellows performed all the measurements , using a systemized approach to decrease variability ; in addition , consultations between reviewers took place .\nsubjects without transverse process dysplasia were classified as normal ( type 0 ) , and those with dysplastic transverse process were classified according to the castellvi radiographic classification system ( table 1 ) .\nthe incidence of sacralizations in the two groups was reported , and the anomaly was compared according to the groups .\nstatistically significant differences were evaluated by using contingency tables with fisher 's exact test for categorical variables .\nthis test was used to compare statistically the differences between the two groups according to having sacralization .\nin g1 , the average age was 39.03 15.9 years ( 1673 years ) .\nof these patients ( 281 women , 219 men ) , 106 were classified as positive for sacralization , with a gender distribution of 54 ( 19.22% ) women and 52 ( 23.74% ) men .\nof the total number of patients ( 500 ) seen , 12 ( 2.4% ) had lumbarization . according to sacralization classification ,\nthe most common anatomical variant was castellvi type ia ( 6.8% ) , followed by type ib ( 5.4% ) , type iia ( 1.6% ) , type iib ( 1.8% ) , type iiia ( 1.4% ) , type iiib ( 3.4% ) , and type iv ( 0.8% ) . in g2 ,\nof these cases ( 297 women , 203 men ) , 84 were classified as positive for sacralization , with a gender distribution of 39 ( 13.13% ) women and 45 ( 28.48% ) men .\nof the total number of cases ( 500 ) seen , 13 ( 2.6% ) had lumbarization . according to sacralization classification ,\nthe most common anatomical variant was castellvi type ia ( 6% ) , followed by type ib ( 4.2% ) , type iia ( 2% ) , type iib ( 1% ) , type iiia ( 0.8% ) , type iiib ( 1.6% ) , and type iv ( 0.8% ) .\nno statistically significant difference was found between the groups according to the presence of sacralization ( p = 0.09 ) ( table 4 ) .\nthe incidence of sacralization has been reported as 4% to 36% in the general population [ 1 , 6 , 9 , 1317 ] .\nits frequency in the low back pain population ranges from 6% to 37% [ 4 , 5 , 10 , 12 , 1821 ] .\nnumerous studies have found no significant correlation between sacralization and low back pain [ 3 , 5 , 7 , 13 , 22 ] , while others have [ 912 , 21 , 23 ] .\nauthors who found no significant correlation [ 7 , 8 , 16 ] have concluded that the incidence of transitional vertebra is equal in those with and without back pain , rendering it only an incidental finding on imaging .\nfrymoyer et al . have determined similar rates of radiological abnormalities in three groups of patients : no lbp , moderate lbp , and severe lbp .\nhave reported the incidence of sacralization to be 13% in patients with lbp and 11% in their control group .\nour study found an incidence rate of 21.2% for sacralization in patients , 16.8% in control group .\ndemonstrated that the abnormal vertebra does not constitute a risk factor for spine degenerative changes but , when degeneration occurs , it focused on the suprajacent level of the transitional vertebra .\nmany of the authors with lower estimations used more stringent criteria to count a vertebra as transitional , while other authors did not clearly state all of the inclusion criteria . while elster and hsieh et al . reported prevalence as low as 7% and 5.9% , respectively , and delport et al . observed a rate of 30% , they were based on articulation or fusion of at least one transverse process and presence of an intervertebral disc caudal to the transitional segment , ultimately failing to recognize our most common subtype \ntype i. this leaves the current estimates of those with a transitional vertebra in the range of 6%37% in those seeking healthcare for low back pain , either slightly or significantly higher than the range of 4%36% commonly reported as the number with sacralization in the general population .\nthis large fluctuation in estimates for the general population amplifies the difficulties in determining the significance of the percentage that we found in our patients .\ncastellvi et al . reported a 30% prevalence on his low back pain population .\napazidis et al . found 35.6% prevalence of sacralization in their studies of 211 lumbar spine subjects who had no pain .\ntheir most commonly found pathology was type ia ( 14.7% ) , as in our study .\na great deal of the controversy surrounding the association of sacralization and lbp is the result of an incomplete understanding of the variation present at the lumbosacral junction , as well as the lack of a comprehensive classification scheme that can be used to differentiate lumbosacral variation according to morphological , developmental , and clinical variants .\ntherefore , a comprehensive understanding of normal and abnormal variations at the lumbosacral junction and a precise classification system are needed to investigate more thoroughly the association between sacralization and lbp .\ndifferences between the classification systems are likely the cause of much of the disagreement ; small sample size may also contribute .\nthe controversy in the literature centers on the issue of whether or not sacralization cause low back pain .\nfirst , an understanding of the variation present must be achieved , complete with a standard , convenient way to categorize that variation .\nsecond , the possible connections among the categories and both frequencies and intensities of low back pain must be investigated as thoroughly as possible .", "answer": "objective . \n the aim of this study was to determine , by plain radiography , if there is a relationship between sacralization and low back pain . methods . \n five hundred lumbosacral radiographs of low back pain patients and 500 control groups were examined . \n data collection consisted of the subject 's age at the time of imaging , gender , number of lumbar vertebral bodies , and bilateral height measurement of the lowest lumbar transverse process . \n dysplastic transverse processes were classified according to the castellvi radiographic classification system . \n the incidence of sacralization in patients and the control groups was reported , and the anomaly was compared according to the groups . results . of these patients groups , \n 106 were classified as positive for sacralization , which resulted in an incidence of 21.2% . \n the most common anatomical variant was castellvi type ia ( 6.8% ) . in the control group , \n 84 were classified as positive for sacralization , which resulted in an incidence of 16.8% . \n no statistically significant difference was found between the groups for having sacralization ( p = 0.09 ) . \n discussion . \n the relationship between sacralization and low back pain is not clear . because of this controversial future studies need to focus on identifying other parameters that are relevant to distinguishing lumbosacral variation , as well as corroborating the results obtained here with data from other samples .", "id": 821} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npersistence of virulent microorganisms and their byproducts in the root canal system , or the surrounding tissues , following initial endodontic treatment , is the main cause for treatment failure .\nit has been reported that failing root canal treatments associated with periradicular pathosis frequently demonstrated fungi colonization .\nthe exact factors affecting the colonization of the root canal by fungi are not completely understood .\nit seems that the most common predisposing factors are certain intracanal medicaments , local and systemic antibiotics , and previous unsuccessful endodontic treatment .\nit has been hypothesized that the reduction of specific strains of bacteria in the root canal during endodontic treatment may allow fungi overgrowth in the low nutrient environment .\nin addition , it is possible that fungi , such as c. albicans , may gain access to the root canal from the oral cavity as a result of poor asepsis during endodontic treatment procedures or because of coronal leakage .\nin fact , the presence of c. albicans in root canals was found to be directly associated with its presence in the oral cavity of the same patients .\nfailure of initial endodontic treatment can often be treated successfully by retreatment or endodontic surgery .\nelimination of the microbial flora and infected tissues as well as a complete seal of the root canal system , to prevent future recontamination , will enhance treatment success . in this\nregard , mineral trioxide aggregate ( mta ) has become a popular material to seal off communications between the root canal system and the external surface of the root .\nit has been mostly used as a retrograde filling material during apical surgery and as a sealant of root perforations .\nhowever , mta is difficult to use because of its longer setting time and poor handling properties .\nmta ( proroot mta , dentsply / tulsa dental , tulsa , ok ) is marketed in gray - colored and white - colored preparations ; both are 75% portland cement , 20% bismuth oxide , and 5% gypsum by weight .\nrecently , the use of the white - colored preparation became more popular because of esthetic considerations .\nmta is a powder that consists of fine hydrophilic particles that in the presence of water , or moisture , forms a colloidal gel that solidifies to form hard cement within approximately 4 h. the principal constituents of the gray - colored formula are tricalcium oxide , tricalcium silicate , bismuth oxide , dicalcium silicate , tricalcium aluminate , tetracalcium aluminoferrite , and calcium sulfate dihydrate .\nit has been reported that a fixed concentration of white - colored mta was effective against c. albicans \n in vitro for periods of up to 3 days .\nit has also been shown that white - colored mta in concentration of 50 mg / ml was effective in killing c. albicans for periods of up to 3 days , whereas lower concentrations were not as effective . in another study ,\nfungal growth occurred during 1-h incubation in both freshly mixed and 24-h set gray and white mta cements , whereas by increasing the incubation time , no fungal growth was observed in 24 and 72 h. it was also reported that both gray - colored and white - colored mta in concentrations of 50 mg / ml and 25 mg / ml were effective in killing c. albicans for periods up to 1 week .\nlower concentrations of gray - colored mta might still be effective , whereas lower concentrations of white - colored mta might not .\nhowever , the antifungal effect of mta on multiple strains of c. albicans over longer periods of time is less investigated .\nthe purpose of this study was to evaluate the antifungal action of various concentrations of white - colored mta against seven different c. albicans strains for various exposure periods using the tube dilution test .\nfresh mix of white - colored mta ( pro - root mta , batch # 05002015 , dentsply / tulsa dental , tulsa , ok ) was prepared at concentrations of 100 , 50 , 25 , and 12.5 mg / ml by dilution with distilled water .\neach freshly prepared mix was added to a broth tube containing sabouraud 's liquid medium ( hi - media laboratories , mumbai , india ) .\na total of 1287 broth tubes were prepared and divided into seven sets with experimental groups of 11 tubes each and control groups .\nbroth tubes without mta served as positive control and tubes without c. albicans served as negative control .\nthe antifungal action of mta against c. albicans was evaluated by using the tube dilution test .\nstock cultures of six strains of c. albicans clinically isolated from the oral cavity ( strains 1 - 6 : c-89 , e-175 , c-304 , e-259 , c-176 , and e-170 ) and a standard strain ( strain 7 : microbial type culture collection ( mtcc ) 3017 ) were obtained .\nfresh inoculate of the microorganism was prepared by growing overnight cultures until a complete suspension of growth was achieved .\nthe cultures were diluted in a pre - warmed broth to achieve a final density of 10 colony - forming unit ( cfu)/spot .\none - milliliter aliquots of the test c. albicans were taken from the broth culture and added to sterile capped test tubes of each experimental and positive control group .\nall experimental and control groups were then incubated at 37c and evaluated at 1- , 24- , 72- , and 168-h ( 7 days ) time periods . at each time period\n, 0.1 ml of samples from each tube was subcultured on sabouraud 's dextrose agar plates ( hi - media laboratories , mumbai , india ) .\ndifferences among the groups were statistically analyzed using kruskal wallis and mann whitney u tests ( statistical package for the social sciences ( spss ) 7 software ) .\nif the calculated critical values were at least as large as the respective critical values at the 0.05 level , then calculations were considered statistically significant in this study .\ngenerally , a direct correlation was found between mta concentrations and its inhibition effect on c. albicans growth .\ndiffering behavior patterns of various strains of c. albicans were also seen [ table 1 ] .\nstrains 5 , 6 , and 7 displayed intermediate resistance to mta , whereas strains 3 and 4 appeared to be most resistant .\nthe negative controls showed no fungal growth at any time period , whereas the positive controls always showed fungal growth .\neffect of various mta concentrations on growth of c. albicans strains statistically , a significant difference was found between tubes containing either strain 3 or 4 and tubes containing other strains at all mta concentrations at the 1-day time period ( p < 0.001 ) .\na significant difference was found between tubes containing strain 3 and tubes containing other strains at mta concentrations of 12.5 and 25 mg / ml at the 3-days time period ( p < 0.001 ) .\na significant difference was also found between tubes containing 12.5 mg / ml and tubes containing higher concentrations of mta at the 7-days time period ( p < 0.001 ) .\nthe method used in the present study was the tube dilution test , which is an effective method to evaluate the antifungal and antibacterial properties of any filling material or solution .\nit was considered appropriate for evaluating the antifungal activity of mta , which has a low solubility and diffusibility . c. albicans was the test organism in this study .\nit is a frequent colonizer of the oral cavity , and multiple unrelated strains showing varying pathogenicity may be present in the same individual . mechanisms of pathogenicity of different strains may include the power of adaptability to a variety of environmental conditions attributable to the switching of gene expression dictated by environmental changes and evasion and immunomodulation of the host defenses by different mechanisms . c. albicans is frequently associated with failing root canal treatments and has the ability to form biofilms on different surfaces , which makes it more pathogenic than species that are less able to form biofilms .\nas it may be involved in cases of persistent and secondary infections , usually present during apical surgery and perforation repair procedures , the antifungal action of the repair material may further assist in the management of such infections and enhance tissue healing . in this study ,\ngrowth of seven strains of c. albicans in four concentrations of mta was assessed for periods of up to 7 days .\nonly one strain showed relative resistance even after 3 days at the lower mta concentration of 12.5 and 25 mg / ml .\nrecurrence of fungal growth was seen with three strains at mta concentration of 12.5 mg / ml after 7 days .\nit might indicate that mta only exhibits a fungistatic action at lower concentrations , whereas a fungicidal action may be expected at higher concentrations .\nthis highlights the significance of using seven strains in the present study . in a previous study ,\nal - nazhan and al - judai reported white - colored mta to be effective in killing c. albicans \n in vitro for a period of up to 3 days .\nhowever , in that study a higher concentration of mta was used . in another in vitro study , al - hezaimi et al .\n, assessed the antifungal action of different concentrations of white - colored mta against c. albicans \n in vitro .\nwhite - colored mta in concentration of 50 mg / ml was effective in inhibiting c. albicans for periods of up to 3 days , whereas lower concentrations were not effective .\nmohammadi et al . , observed fungal growth during 1-h incubation in both freshly mixed and 24-h set gray and white mta cements , whereas by increasing the incubation time , no fungal growth was observed in 24 and 72 h. another study also showed that both white and gray mta in concentrations of 50 and 25 mg / ml were effective in inhibiting c. albicans for periods of up to 7 days .\nkangarlou et al . , assessed the antifungal activity of proroot mta and mta - angelus and concluded that mta - angelus was a more effective antifungal agent compared with proroot mta at concentrations of 50 and 100 mg / ml .\nregarding the antifungal action of mta , it has been shown that the mechanism of action of mta involves the dissolution of calcium oxide , which increases ph by releasing ca and oh . the high ph increases the permeability of cell membranes with leakage of intracellular components .\nwaltimo et al . , reported that c. albicans survived incubation in calcium hydroxide solution for 1 and 6 h and was killed after 6 h of incubation .\nferguson et al . , found that an aqueous solution of calcium hydroxide had no activity against c. albicans .\nhowever , when maintained in direct contact with c. albicans cells , calcium hydroxide paste was very effective in killing this fungus .\ntherefore , it can be assumed that mta is more effective in killing c. albicans when placed in direct contact with the fungus .\nin addition , samiei et al . , reported that adding silver nanoparticles to mta improved its antimicrobial efficacy . in conclusion\n, it appears that under the conditions of this study , white - colored mta in concentrations of 100 and 50 mg / ml is effective in inhibiting the seven tested strains of c. albicans for periods up to 1 week .\nhowever , the antifungal activity of white - colored and gray - colored mta over longer periods of time on more number of strains merits further investigation .", "answer": "aim : the purpose of this study was to evaluate the antifungal action of various concentrations of white mineral trioxide aggregate ( mta ) against seven different strains of candida albicans using the tube dilution test.materials and methods : fresh mix of mta was prepared at concentrations of 100 , 50 , 25 , and 12.5 mg / ml and added to a broth tube containing sabouraud 's liquid medium . \n a total of 1287 broth tubes were prepared and divided into experimental and control groups . \n stock cultures of seven strains of c. albicans were obtained . \n fresh inoculate of the microorganism was prepared by growing overnight cultures . \n aliquots of the test c. albicans were taken and added to the test tubes . \n all tubes were incubated at 37c for 1- , 24- , 72- , and 168-h time periods . at each time period , the presence of c. albicans colonies was assessed.statistical analysis used : differences among the groups were statistically analyzed using kruskal wallis and mann whitney u tests.results:results showed that one strain showed resistance even after 3 days at the lower mta concentrations of 12.5 and 25 mg / ml . growth reoccurred with three strains at mta concentration of 12.5 mg / ml after 7 days . \n a significant difference was found between strain 3 and other strains at mta concentrations of 12.5 and 25 mg / ml at the 3-days time period and between tubes containing 12.5 mg / ml and tubes containing higher concentrations of mta at the 7-days time period.conclusion:white mta in concentrations of 100 and 50 mg / ml is effective in inhibiting the seven tested strains of c. albicans for periods up to 1 week .", "id": 822} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 65-year - old man without any symptoms was referred for an operation on the aortic root and ascending aortic aneurysm .\nhe had undergone a total correction of tetralogy of fallot ( tof ) and aortic valve replacement with mechanical valvular prosthesis 22 years earlier ( in 1987 , at the age of forty - three ) . in august 2009 ,\na huge aneurysmal dilatation ( 9 cm ) of aortic root and proximal ascending aorta , severe tricuspid regurgitation , and good left ventricular ejection fraction were found on echocardiography .\ncomputed tomography showed a huge saccular aneurysm of the aortic root and proximal ascending thoracic aorta ( fig .\n1 ) . the patient underwent a bentall procedure involving a composite conduit with a mechanical valvular prosthesis .\nthe operation also included pulmonary valve replacement using a bioprosthesis , tricuspid annuloplasty , subaortic pannus resection , maze procedure , and coronary artery bypass surgery ( saphenous vein to proximal right coronary artery ) .\nbecause the right coronary artery orifice was deviated to the left side and was close to the aortic annulus , coronary artery bypass surgery was chosen despite availability of the button technique .\nafter the operation , there was the microscopic finding of cystic medial degeneration in the ascending aortic wall ( fig .\nhe was discharged on his 37th postoperative day . at follow - up , he remains well 17 months after this latest procedure .\nin 1997 , dodds and colleagues described the first series report about progressive aortic regurgitation and aortic root dilatation after complete , uncomplicated repair of tof .\na long - standing volume overload of the aortic root may cause aortic root dilatation in adults with a repaired tof .\nthe right to left shunt through the ventricular septal defect in unrepaired tof increases the volume overload effect on the aortic root . another causative mechanism for progressive aortic root dilatation\nintrinsic histological changes were found in tof patients ; including medionecrosis , fibrosis , cystic medial necrosis , elastic fragmentation and elastic lamellae disruption .\nour patient had initial reparative surgery at the age of forty - three in 1987 .\nthe phrase of the enlarged aorta was described in the record of the first operation .\n, we did not know why correction was not performed in the initial operation . in 2002 ,\nan operation for ascending aortic aneurysm was recommended , but he refused any surgery at that time .\nthe pathologic conditions of aortic root and ascending aorta in repaired tof are no longer a benign problem . in recent reports ,\nthese are the first reports of aortic dissection in tetralogy of fallot . after an initial curative operation for tof , meticulous monitoring of aortic root and ascending", "answer": "surgical repair of the tetralogy of fallot is one of the most successful operations in the treatment of congenital heart diseases . \n we report the case of a 65-year - old man who had an aortic valve replacement at the time of complete repair of the tetralogy of fallot at the age of forty - three . \n he subsequently had progressive aortic root and ascending aorta dilation to 9 cm . \n the aortic root and ascending aorta replacement was done using a composite valve - graft and was performed along with other procedures . \n thus , meticulous follow - up of aortic root and ascending aorta after corrective surgery for tetralogy of fallot is recommended following initial curative surgery .", "id": 823} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nThe development of a dedicated polymer support for the solid-phase oligosaccharide synthesis\\xe2\\x80\\xa0\n\nPaper sections:\n\nWith the advances in the field of glycosciences and an increasing number of structures elucidated and applied in all areas of the field, the need for reliable approaches to the synthesis of glycans has grown exponentially.1 Traditional glycan synthesis in solution involves iteration of glycosylation and deprotection steps with interim purification for practically every intermediate. Some advanced strategies based on either chemoselective or selective activation of building blocks help to streamline the oligosaccharide assembly significantly.2 However, no universal route to the chemical synthesis of glycans can be established, which dramatically hinders progress in glycosciences, whereas other biopolymers, peptides3,4 and oligonucleotides,5 can be produced by machines. Solid-phase synthesis eliminates the need for conventional reaction work-up and purification of intermediates,6\u20138 and offers promising automation amenability. Since early efforts in 2001,9 Seeberger et al. developed a dedicated automated oligosaccharide synthesizer in 201210 that was later commercialized as Glyconeer 2.1.11
Also in 2012, we reported High Performance Liquid Chromatography equipment-based Automation (HPLC-A) of solid-phase synthesis.12 The general idea for developing the HPLC-A is that a computer interface coupled with standard HPLC components will allow recording a successful automated sequence as a computer program that can then be reproduced with the \"press of a button.\"
However, solid-phase synthesis of glycans suffers from certain inherent weaknesses. \"The chemistry and biology of carbohydrates has been a Cinderella field,\"13 and the area of solid-phase synthesis wherein everything has been \"borrowed\" from other fields illustrates this problem very clearly. For example, instead of developing dedicated supports, commercial resins designed specifically for peptide or nucleotide solid-phase synthesis14\u201316 are meticulously evaluated to determine their possible suitability for glycan synthesis, which often demands different characteristics.17 While HPLC-A and other automated approaches have a potential to revolutionize the way glycan synthesis is conducted, all current platforms suffer from inherent weakness of solid-phase synthesis as applied to glycans, among which is poor compatibility of existing commercial resins. Reported herein is the first step of our strategic goal to tackle all key weaknesses of the solid-phase synthesis, both automated and manual.
All traditional resins are based on polystyrene, but differ in functionalization/crosslinking, albeit none were designed specifically with the solid-phase synthesis of glycans in mind.18 Seeberger automation platform relies on the Merrifield resin. Our original HPLC-A set-up was based on Tentagel, a polystyrene grafted with PEG chains.12 Later on, we identified JandaJel polystyrene resin crosslinked with tetrahydrofuran-derived chains as a more suitable support for HPLC-A19 due to its better swelling properties compared to the traditional Merrifield resin. Cross-linked polystyrenes are mechanically stable and can be obtained on a large scale from broadly available and inexpensive precursors. However, phenol-based cross-linking used in JandaJel (1, Fig. 1) may potentially have marginal stability under strongly (Lewis) acidic conditions, such as large amounts of trimethylsilyl trifluoromethanesulfonate (TMSOTf)20 commonly employed in the solid-phase synthesis of glycans.
Although this degradation was not thought to significantly hinder general progress, we came to the realization that beads designed for peptides do not have the necessary properties suitable for glycan solid-phase synthesis. Researchers working with polymer-supported glycan synthesis often encounter limited swelling, marginal chemical stability, resin poisoning, reagent trapping, etc. To address this potential weakness, described herein is the investigation of benzyl alcohol-derived ethylene glycol chain cross-linking (2, Fig. 1) due to the anticipated greater stability of such structures under (strongly) acidic reaction conditions.21,22 This type of resin was first synthesized by Itsuno et al.,22 but its application in solid-phase synthesis is unknown. Interestingly, benzylic attachments have been considered by Janda and co-workers,23,24 but were deemed inferior due to their marginal stability toward strongly basic reagents, such as BuLi. To increase the swelling properties in polar protic solvents, we chose to replace the tetrahydrofuran chain used by Janda with diethylene glycol (DEG) derived structure 2 depicted in Fig. 1. Ethylene-glycol,25 its homologs, and other similar molecules24 have been previously investigated as crosslinkers, but the application of such resins in solid-phase synthesis is unknown.22
Crosslinked monomer 2 was synthesized using paravinylbenzyl chloride 3 and diethylene glycol 4 in the presence of NaH in DMF, affording the desired compound in a good yield of 85% (Scheme 1). The cross-linked monomer 2 was then used in the synthesis of a 2% cross-linked polymer 6. For this purpose, a mixture of monomers 2, 3, and 5 in a respective ratio of 2/10/88 (w/w/w) was polymerized in the presence of benzoyl peroxide, sodium chloride, and Arabic gum in water at 85 \u00b0C for 16 h following a procedure previously described by Janda.20 The desired polymer 6 was then purified using a Soxhlet extractor and i-PrOH. The chlorobenzyl group was further functionalized following Gabriel's synthesis protocol, wherein the chloride was displaced with phthalimide in DMF at 55 \u00b0C. The resulting phthaloyl group was then removed with hydrazine hydrate in a mixture of MeOH and chloroform. This two-step procedure produced PanzaGel 7 equipped with the primary amine functional groups (Scheme 1) with a nominal loading capacity of 1.0 mmol g\u22121.
Then, the swelling properties of the polymer were investigated. Swelling was measured following described procedures,26 using a syringe equipped with a sintered frit. The volume of dry resin was measured, then solvent was introduced in the syringe and the mixture was allowed to equilibrate for 1 h. After being vortexed, extra solvent was removed using another syringe. As listed in Table 1, polymer 7 has much better swelling properties when compared to the Merrifield resin, both in polar and non-polar solvents. In addition, polymer 7 showed similar swelling volumes to those reported for JandaJel.20 Notably, PanzaGel exhibits better swelling in MeOH than that of both Merrifield's resin and JandaJel.
A set of experiments was then conducted to determine physical properties of the resin. Thermal degradation properties of PanzaGel were assessed by thermogravimetric analysis (TGA). As shown in Fig. 2, the thermal decomposition of PanzaGel 7 was investigated at various temperatures. PanzaGel was found thermally stable up to 360 \u00b0C, but about 97% weight loss occurs by 460 \u00b0C. To assess the chemical stability of PanzaGel, the polymer was treated with trimethylsilyl trifluoromethanesulfonate, as this Lewis acid was found to degrade JandaJel.20 Upon treatment of 100 mg of resin with 100 \u03bcL of TMSOTf in 1.0 mL of methylene chloride for 1 h, which exceeds the typical conditions employed in chemical glycosylations using polymer supports, no decomposition was observed. The thermal decomposition temperature and the SEM images of the polymer showed no significant difference before and after the treatment with TMSOTf. PanzaGel treated with TMSOTf decomposed by about 85% upon heating to 600 \u00b0C leaving behind a residue, indicating a chemical structure unaltered by the prolonged contact with the acid.
The prepared polymer was also investigated by scanning electron microscopy. As shown in Fig. 3, polymer 7 was prepared in a shape of monospheres with an average size of 157.64 \u03bcm (average of 30 polymer beads). Nitrogen adsorption/desorption isotherm plots have been used to evaluate the pore volume (Vp) and the surface area (S) of the synthesized material. The total pore volume was calculated as 0.0033 mL g\u22121. The BET surface area was found to be 0.84 m2 g\u22121.
To evaluate synthetic applications of the novel resin, we moved on to synthesize disaccharide 8 and pentasaccharide 9 (Fig. 4). Our labs have recently achieved a full automation of the synthesis of oligosaccharides using a two-way split valve.27 Differently from our previous experimental set up involving reagent delivery with a preparative autosampler,19,27,28 herein we investigated an HPLC system equipped with an analytical autosampler instead. This module is common on HPLC systems, which would allow to broaden the scope of HPLC-A.
To accommodate this adjustment, a higher concentration of donor 11 (0.12 mmol, 7.2 equiv.) were dissolved in 2.7 mL of methylene chloride and the donor solution was split in two vials, containing 1.6 and 1.1 mL of solution, respectively. The autosampler was programmed to draw 500 \u03bcL (0.024 mmol) of donor 11 solution per injection. The autosampler was also programmed to draw 100 \u03bcL (0.025 mmol) of TMSOTf solution in methylene chloride per injection. Donor and promoter were mixed in the needle seat and injected towards the HPLC column, loaded with 50 mg of acceptor-bound resin 10 (0.0165 mmol). The activated donor is allowed to saturate the column for 1.0 min at a flow rate of 1.0 mL min\u22121. After that, the flow rate was lowered to 0.05 mL min\u22121 to maximize the time of exposure of the resin-bound glycosyl acceptor to the glycosyl donor. The flow rate was kept at the minimum level (0.05 mL min\u22121) for 10 min, then increased back to 1.0 mL min\u22121, using fresh CH2Cl2 to wash the column from the unreacted and hydrolyzed donor. This washing step is needed to prepare the resin for new injections of donor 11 and TMSOTf solutions. The same operation was repeated four additional times and the glycosylation sequence was completed by alternating washings with methylene chloride and DMF (see the ESI,\u2020 for details).
This completes the synthetic sequence needed for the synthesis of disaccharide 8. For the synthesis of pentasaccharide 9, the temporary Fmoc protecting group was removed using a 40% solution of piperidine in DMF following the glycosylation step. Three injections of the piperidine solution were performed, and the reaction was followed using the variable wavelength detector set at 301 nm. The sequence was completed by washings alternating CH2Cl2 and DMF. Last, the polystyrene resin was reacidified through injecting 100 \u03bcL of the TMSOTf solution previously used for glycosylation. The two reactions were repeated as needed to afford the target glycan 9. As previously described, the two-way split valve diverts the flow to a collection flask. The compounds are then cleaved using a 1 M solution of sodium methoxide in MeOH/MeOH/CH2Cl2 (1.5/1/1, v/v). Through a series a post-automation steps the target glycans 8 and 9 were isolated in 80% and 30% yields, respectively. Noticeably, both syntheses were conducted at room temperature and without utilizing strictly anhydrous reaction conditions or inert atmosphere.
In conclusion, PanzaGel, a new polystyrene-based resin for polymer supported glycan synthesis has been developed. The resin that was designed specifically for glycan synthesis in mind. PanzaGel incorporated best features of common polymeric supports for peptide synthesis: high stability of Merrifield resin and greater swelling JandaJel. PanzaGel has better swelling properties than used Merrifield resin and swells better in polar solvents than JandaJel. The glycan synthesis performed at the end of this study showcased how the improved polymeric support works in application to the HPLC-A. The target oligosaccharides were obtained using the HPLC-A experimental set-up containing the split valve, similar to that recently introduced by us.27 The current application makes use of a standard HPLC analytical autosampler. New programming/injection sequences were developed specifically for this modified set-up. A new solid support for oligosaccharide synthesis will increase the attractiveness of all synthetic and automated technologies, setting the ground for further improvements, which could include grafting to improve swelling in polar solvents. The synthesis of the new resin is fairly straightforward, and the length of the cross-linker and its composition can easily be varied to achieve best results in terms of swelling, mechanical and chemical stability, flow-through applicability, and loading capacity. PanzaGel can be synthesized in many shapes and dimensions: we are currently pursuing the synthesis and application of monolithic resins in a cylinder shape that are more suitable for the in-column, flow-through applications in HPLC-A.
", "answer": "Reported herein is the development of a novel polystyrene-based resin that we named PanzaGel. The resin was equipped with diethylene glycol-derived cross-linker with the dedicated application to polymer supported glycan synthesis in mind. After investigating its swelling properties and obtaining encouraging data for its chemical and thermal stability we accessed the amenability of PanzaGel to the HPLC-based platform for the automated synthesis. Comparable glycosylation results to those with traditional supports have been obtained in the synthesis of glycans up to pentasaccharide that was obtained in 30% overall yield. The automated synthesis set-up implemented a common analytical autosampler for delivering all reagents for all steps of the glycan synthesis and cleavage.", "id": 824} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n pulmonary hypertension is an increasingly recognized complication of sickle - cell anaemia and a risk factor for early death [ 14 ] .\nrecurrent episodes of acute and subacute pulmonary crises reflecting in situ sickling within the lung has been postulated to be the primary event leading to pulmonary hypertension .\nhaemolysis may participate in its pathogenesis by limiting nitric oxide ( no ) bioavailability and producing vasculopathy [ 5 , 6 ] . \nan initial study in howard university , usa , using echocardiographic assessment of tricuspid valve regurgitant jet velocity 2.5 m / sec as diagnostic criteria , demonstrated pulmonary hypertension in 32% of adult sickle - cell patients , and the prevalence appeared to increase with age of the patients . in patients\nbetween 40 and 49 years old , the prevalence was 40% and increased to 5560% by age 50 and above .\nother studies have documented prevalence rates between 20 and 40% [ 4 , 810 ] .\nsickle - cell anaemia patients with pulmonary hypertension have a significantly increased mortality rate compared with patients without pulmonary hypertension .\nsutton and colleagues reported 40% mortality rate in sickle - cell patients with pulmonary hypertension at 22 months after diagnosis ( odd ratio 7.86 ; 95% confidence interval = 2.6323.4 ) compared with sickle - cell patients without pulmonary hypertension .\ncastro et al . in a study of 34 adult sickle - cell patients who underwent right heart catheterization for evaluation of pulmonary hypertension found increased pulmonary artery pressure in 20 ( 58.8% ) on initial catheterization . during 2345 months of\nfollow up , 11 of these 20 ( 55.0% ) died compared with 3 of the 14 without pulmonary hypertension ( 21.0% ) .\nevery 10 mmhg increase in mean pulmonary artery pressure was associated with 1.7 increase in mortality ( 95% confidence interval = 1.12.7 ; cox proportional hazard model , p = 0.028 ) .\nthe study was aimed at comparing the clinical and electrocardiographic findings in sickle - cell anaemia patients with raised pulmonary artery pressure with those of patients without pulmonary hypertension .\nthe study was carried out in the adult outpatient sickle - cell clinic and the cardiac centre of the university of nigeria teaching hospital ( unth ) , enugu , nigeria .\nthe study subjects were drawn from adult patients ( age 18 years ) , attending the adult sickle - cell clinic of the hospital , who had haemoglobin genotype ss on haemoglobin electrophoresis , were in steady state , and consented to participate in the study .\nsteady state is defined as absence of any crisis in the preceding four weeks , absence of any symptoms , or signs attributable to acute illness .\na total of sixty two sickle - cell anaemia patients , and sixty two age- and sex - matched normal controls were studied . \nresting 12-lead electrocardiography was performed on all subjects using cardioline ar-600 model electrocardiography machine at a paper speed of 25 mm / s and standardized at 0.1 mv / mm . a single observer analyzed the electrocardiogram .\nmeasurements of the heart rate , cardiac axis , pr- interval , qrs duration , and qtc interval were done in the standard fashion .\nheart rate correction of the qt interval was performed using bazett 's formula ( qtc = qt/ rr ) .\nthe dispersion of p - wave , qrs , and qtc intervals was measured manually under magnifying glass by the same observer and was taken as the difference between the maximum and minimum values of each parameter on standard 12-lead electrocardiogram . left ventricular hypertrophy on electrocardiogram was based on sokolow and lyon voltage criteria , while right ventricular hypertrophy was based on the criteria described by allenstein and mori ( dominant or tall r - waves or rs pattern in a vr , v1 , and v2 with deep s - wave in i , avl , v5 , and v6 ) . \nechocardiography was done using hewlett packard sonos 2500 echocardiography machine with 3.7 mhz transducer .\npulmonary artery flow acceleration time was obtained from a doppler signal of the pulmonary flow in the parasternal short - axis view at the aortic valve level and was described as the time from onset to peak flow velocity . the mean pulmonary artery pressure ( mean pap )\nwas calculated from the formula : mean pap ( m \n m / h \n g ) = 90 ( 0.62 a \n t ) , where at is the acceleration time of the pulmonary artery flow .\npulmonary hypertension was defined as calculated mean pulmonary artery pressure 30 mm / hg [ 4 , 7 ] .\nethical clearance for the study was obtained from the ethical committee of the university of nigeria teaching hospital , enugu , nigeria .\nthe declaration of helsinki 's recommendations for guiding physicians in biomedical research involving human subjects were followed .\ndata were presented as means standard deviation for continuous variables and as proportions for categorical variables\n. comparisons of continuous variables between groups were made with independent student 's t - test .\nfor discrete variables , distribution between groups was compared with chi - square test and fishers exact test as appropriate ( where an expected cell is less than 5 ) .\nmultivariate pearson 's correlation coefficient was used to determine the relations between clinical , electrocardiographic data and mean pulmonary artery pressure .\nall statistical analyses were carried out using the statistical packages for social sciences ( spss inc . ,\nchicago , illinois ) software version 11.0 and epi - info version 3.4 . statistical tests with 2-tailed probability values less than 0.05 were considered statistically significant .\nthe age , gender , and anthropometric parameters of the patients and controls are shown in tables 1 and 2 . \nvalues for pulmonary artery pressure in the patients and controls are shown in table 3 .\nelevated pulmonary artery pressures ( pap ) as defined by pap 30 mmhg was demonstrated in ( 26 ) 41.9% of patients with sickle - cell anaemia and in ( 2 ) 3.2% of the controls ; \n = 26.571 , df = 1 , p < 0.001 ( figure 1 ) .\np - wave duration , qtc interval , and qtc dispersion were increased in patients with pulmonary hypertension ( table 5 ) . \nsignificant correlation was found between mean pap and ( 1 ) frequency of crisis ( spearman correlation = 0.320 ; p = 0.011 ) , ( 2 ) body mass index ( pearson 's correlation = 0.297 ; p = 0.019 ) , and ( 3 ) qtc interval ( pearson 's correlation 0.261 ; p = 0.040 ) , ( table 6 ) .\nthe prevalence of pulmonary hypertension in adult nigerian sickle - cell anaemia patients in this study was 41.9% .\nthis value is slightly higher than previous report of 25% by aliyu et al . in northern nigeria .\nhowever , in that study , neither the mean pap nor the mean age of the subjects was stated . \nprevious studies have relied on tricuspid regurgitant jet velocity as an indirect estimate of pap .\nthis has resulted in an underestimation of the prevalence of pulmonary hypertension in sickle - cell anaemia patients .\nresults of right heart catheterization for evaluation of pulmonary artery pressures in sickle - cell patients have shown prevalence rate of 58.8% .\nautopsy studies suggest that up to 75% of sickle - cell anaemia patients have histological evidence of pulmonary arterial hypertension at the time of death .\nmean pap derived from the echocardiographic estimation of pulmonary artery flow acceleration time in steady - state patients as was used in this study has been shown to correlate significantly with values from cardiac catheterization . \nseveral studies have corroborated the role of vaso - occlusive crisis and acute chest syndrome in initiating nitric oxide depletion resulting in the pathological changes in pulmonary hypertension [ 6 , 19 ] .\nthis study identified a positive correlation between pulmonary artery pressure and frequency of vaso - occlusive crisis . \npatients with pulmonary hypertension were found to have reduced body mass index when compared with patients without pulmonary hypertension .\nthis difference could be due to increased disease severity in patients with pulmonary hypertension . \nrecurrent insitu vaso - occlusive crisis in the pulmonary vascular bed with resultant pulmonary hypertension and right ventricular hypertrophy has been demonstrated in sickle - cell disease patients .\nthis is in keeping with the finding by this study of a significantly increased prevalence of right ventricular hypertrophy in patients with pulmonary hypertension .\nright ventricular hypertrophy in these patients explains the significant positive correlation between pulmonary artery pressure and qtc interval .\nthe significance of increased p - wave duration and the spatial dispersion of qtc - interval noted in this study in patients with pulmonary hypertension are unclear .\nqtc dispersion is a measure of the disparity among qtc intervals in various electrocardiographic leads and reflects the variability of myocardial repolarization .\nthis corroborates the finding in a study by akgul et al . in turkey which recorded higher qtc dispersion in sickle - cell patients with pulmonary hypertension .\n pulmonary hypertension in adult sickle - cell anaemia patients is significantly associated with electrocardiographic evidence of right ventricular hypertrophy , increased p - wave duration , qtc interval , and qtc dispersion and correlates significantly with frequency of vaso - occlusive crisis and qtc interval .\nthe observations by this study tend to suggest that these parameters could be useful for early detection and prevention of pulmonary hypertension in patients with sickle - cell anaemia .", "answer": "pulmonary hypertension is an emerging complication of sickle cell anaemia with associated increased risk of mortality . in order to evaluate the clinical and electrocardiographic findings in adult sickle - cell patients with pulmonary hypertension , \n a cross sectional study was conducted on sixty two sickle cell anaemia patients and sixty two age and sex matched normal controls . \n elevated pulmonary artery pressures ( pap ) , defined by pap 30 mm hg on echocardiography , was demonstrated in 41.9% of patients with sickle cell anaemia and in 3.2% of the controls ; \n 2 = 26.571 , p < 0.001 . \n right ventricular hypertrophy , increased p - wave duration , qtc interval , and qtc dispersion were significantly associated with pulmonary hypertension . \n significant correlation was found between mean pap and ( 1 ) frequency of crisis ( spearman correlation = 0.320 ; p = 0.011 ) , ( 2 ) body mass index ( pearson 's correlation = 0.297 ; p = 0.019 ) , and ( 3 ) qtc interval ( pearson 's correlation 0.261 ; p = 0.040 ) . pulmonary hypertension in adult sickle anaemia patients is associated with electrocardiographic evidence of right ventricular hypertrophy , and correlates significantly with frequency of vaso - occlusive crisis , and qtc interval . \n the observations by this study tend to suggest that these parameters could be useful for early detection and prevention of pulmonary hypertension in patients with sickle cell anaemia .", "id": 825} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndiscoveries of restriction enzymes by hamilton smith and daniel nathans , and reverse transcriptase by howard temin and david baltimore in the 1970s set the stage for an explosion in molecular and clinical genetics .\narmed with a sufficient amount of the mrna product of a gene such as the beta globin gene , investigators could now produce a radioactive dna copy ( cdna ) of the mrna and use it as a valuable probe of gene expression .\ncloned into an expression plasmid and transduced into an appropriate cell , the cdna would produce mature beta globin mrna , and cdnas could be manipulated at will in what became the era of recombinant dna technology .\nthe new discoveries were greeted with enthusiasm by most biologists and clinical investigators but with mounting horror and suspicion by many members of the public and their elected officials , as well as some academics .\nfrankensteins were thought to be loose in biomedical laboratories ; monsters would be created ; plagues of vicious e. coli would be loosed on an innocent population ; mad scientists would forever contaminate the food supply ; the new genetics would lead to a resurgence of social darwinism .\nthe specter of nazi medicine roiled some faculty meetings and communities in which the science was rapidly advancing .\nrules and restrictions were demanded that would deliberately inhibit the work . to their credit , leaders of this new genetics revolution met in asilomar california , where they established laboratory standards intended to reassure themselves , their colleagues , and the general population that gene manipulation could be rendered safe and useful .\nwhile eager clinical investigators hoped to apply the new genetics in the treatment of inherited diseases , cooler heads recognized that the technology was not sufficiently powerful or predictable .\nthe more cautious advised the national institutes of health to be very wary of human application because the biological ' rules of the game ' had not yet been established .\nthat did not stop an american clinical entrepreneur from injecting beta globin cdna into the bone marrows of thalassemic patients in italy and israel .\nhis reward was failure and opprobrium , and academic medicine encountered a congress increasingly determined to surround clinical research with an ever - growing net of regulation .\nhow could a cdna be introduced efficiently into a rare , quiescent , mammalian cell , such as a bone marrow stem cell , remain potentially active , and be sufficiently expressed when that stem cell developed into a hematopoietic precursor and subsequently fully differentiated functional blood cell ?\nfurthermore , could a defective gene be actually replaced in human cells in a targeted fashion by a normal counterpart and still maintain high transcription efficiency , or would such ' plug and socket ' technology be so inefficient that correction would be impossible ?\ninstead , could cdnas such as a beta globin cdna be carried into the target cell chromosomes on the back of a virus , such as a retrovirus , and could the transduced sequence express its mature mrna regardless of its genomic location ?\nthe idea of a retrovirus as a gene - transfer agent was first seen as dangerously oncogenic , until 1983 and 1984 when mann , mulligan and baltimore devised cell lines that would produce replication - defective retroviruses that still exploited the capacity of the viruses to incorporate themselves efficiently in the dna of dividing cells . for the most part ,\nthe modified retroviral vectors infected human cells at comfortingly low multiplicities of infection . shortly after this\n, williams and mulligan and dick and bernstein , and their colleagues , showed that murine bone marrow cells could be transduced with defective retroviruses carrying cdnas , and that mature nucleated blood cells would carry the foreign cdna for weeks , proving that the murine hematopoietic stem cell , despite its very low rate of division , could be so transduced .\nbut the percentage of infected cells was very low and expression of the transferred gene was vestigial .\nthe results suggested that successful gene transfer with cdnas borne on replication - defective retroviruses would require high recombinant viral titer , cell culture systems that would encourage stem cell division without differentiation , and a setting in which target cells would have a selective advantage following gene transfer .\nthe entire field of gene therapy was energized by the findings of williams and dick and their colleagues , but the barriers to translation and clinical application were soon found to be almost insurmountable .\nthe slow pace prompted orkin and motulsky to lower their expectations for immediate clinical application , and focus instead on solving the basic technical and biological problems . in an attempt to gain some clinical traction , blaese and his colleagues introduced retroviral cdna ex vivo into the mature t cells of patients with immunodeficiency due to mutations in adenosine deaminase .\nthe treatment provided little if any clinical benefit , and the risk of malignancy was obviously high because the t cells were influenced to divide in culture in order to enhance transduction .\nconcerns about unwieldy and potentially unsafe clinical research protocols began to mount in the united states .\nfour levels of review , the recombinant dna advisory committee , individual institutional review boards , individual institutional biosafety committees , and the food and drug administration all established barriers that slowed the pace of gene therapy clinical research to a crawl .\nthis necessary regulatory environment was onerous enough , but it became even more obstructive when investigators at the university of pennsylvania performed a study of gene replacement in a rare metabolic disorder using adenovirus as a vector in order to infect non - dividing liver cells .\none young adult with the disease died after a high titer of virus was administered .\nan investigation revealed that the gene therapists had a financial stake in the company that produced the vector .\nthat revelation initiated an even higher burden of regulation and added massively to a growing concern about conflict of interest in clinical research - a conflict that continues to roil academic waters to this day .\nmeanwhile , after four decades of development , the clinical application of allogeneic hematopoietic stem cells in transplantation for the treatment of congenital bone marrow diseases was moving ahead reasonably briskly ( sans gigantic regulatory hurdles ) .\nthis form of cell - based therapy , though initially applicable in only the 25 - 30% of patients with histocompatible donors , was associated with success in several patients with severe immunodeficiencies , congenital bone marrow failures of several types and even the inherited hemoglobin disorders .\nadenovirus vectors were thought to be too immunogenic to be useful but they and their cousin , the tiny adeno - associated virus , were considered to be worthy of evaluation in the transduction of non - dividing cells such as liver cells or endothelial cells .\nindeed , high and her co - workers have made quiet progress in the correction of canine hemophilia with adeno - associated virus .\nmost groups interested in hematopoietic targets or cancer vaccine protocols continue to focus on defective murine leukemia viruses or lentiviruses .\nthe latter are thought to have a higher capacity than murine leukemia viruses to integrate within the dna of non - dividing cells .\nboth the science and the regulatory apparatus seemed to be daunting , and the funding was fragmented and difficult to obtain . but in 2002 cavazzana - calvo and his colleagues blew new life into the field when they made the startling announcement that they had successfully treated nine of ten patients with x - linked severe combined immunodeficiency ( scid ) , utilizing a fairly standard murine leukemia viral vector that carried the common gamma chain of the interleukin-2 receptor into autologous bone marrow cells .\nshortly thereafter , however , cynicism returned when the authors reported that several of the patients had developed t cell leukemia .\ncareful work by the investigators revealed that the long terminal repeat ( ltr ) of the vector may have a predilection for the lmo2 proto - oncogene on chromosome 11 .\nbut even random integration of the ltr at the lmo2 site would favor selection of such cells . the lmo2 proto - oncogene is often activated by translocation ( 11:14 ) in t cell leukemia . clearly , the gene - corrected immunocytes had a survival advantage , but the malignant t cells had an even greater survival advantage as well as a growth advantage .\nwhat was once a promising new start for gene therapy became an enormous set - back .\nvector safety had always been a pressing issue - now it had become a yawning chasm : of 20 patients with x - linked scid treated by gene transfer in these two trials , 18 are currently alive and with good immune reconstitution , but five have experienced a serious side - effect .\nof these five children , one died of therapy - related leukemia , and one died of complications of a subsequent stem cell transplant that was performed as a result of the failure of gene therapy .\nhave been the results of retroviral correction of oxidase deficiency in chronic granulomatous disease . in two well - described cases ,\ncorrection of granulocyte oxidase deficiency has been achieved but at the cost of clonal proliferation of cells activated at the sites of the mds-1-evi1 , prdm16 or setbp1 proto - oncogenes .\nfurthermore , other in vitro studies have demonstrated similar insertions by lentiviruses bearing beta globin genes . finally , williams and his co - workers have temporarily discontinued their pioneering work on the correction of the deficiency of dna repair pathways in hematopoietic stem cells of patients with fanconi anemia , because they are concerned that current vectors that permit rescue of those cells may induce insertional mutagenesis and leukemia in the treated patients , and that focus should be on developing methods of expanding deficient hematopoietic stem cells in this disease . despite these serious setbacks\nthere have been some recent bright lights . in 2008 , maguire and bainbridge and their colleagues reported progress on the treatment of leber 's optic atrophy with an adeno - associated viral vector applied to the retina . and retrovirally transfected epidermal stem cells have been grown into keratinocytes to correct the lesions of epidermolysis bullosum .\nmore follow - up is needed but the initial results hold promise for local applications of gene transfer .\nan encouraging report emerged at a recent annual meeting of the european society of gene and cell therapy .\nlentivirus vectors have been used to transduce hematopoietic stem cells in x - linked adrenoleukodystrophy , a progressive demyelinating disease that causes severe debilitation by early teenage years .\nlong - term and stable gene modification has been observed in 20% of myeloid cells , well within the range to reverse phenotypes in some red cell and myeloid disorders .\nfinally , auiti and his colleagues have recently reported highly encouraging results in the treatment of adenosine deaminase deficiency .\nthus , gene therapy of hematopoietic diseases with retroviruses lumbers in choppy straits twixt the scylla of insufficient gene transfer and the charybdis of leukemia , while the therapy of metabolic and coagulation disorders with adeno- and adeno - associated viruses is blunted by immune reponses to the vectors . to committed gene therapists ,\nthese are simply the challenges that they have always faced , while those who are engaged in stem cell transplantation , or in finding better halfway measures that support afflicted patients , work as best they can , all the while hoping that the holy grail of gene replacement will one day become a safe reality .\nthe future could lie in the promising field of site - specific gene correction using modified nucleases , and the conversion of corrected somatic cells such as fibroblasts to functioning hematopoietic stem cells .\ncdna : copy dna ; ltr : long terminal repeat ; scid : severe combined immunodeficiency .\nthe authors are particularly grateful to our colleague david a williams , md , for his contributions to this field and his invaluable assistance during the development of this review .", "answer": "though the field has moved with glacial speed , gene therapies have been carried out successfully in patients with bone marrow disorders including immune deficiencies . \n the field may be poised to move forward more rapidly , but many barriers have yet to be surmounted .", "id": 826} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nakabane virus ( akav ) is an arthropod - borne virus belonging to the genus orthobunyavirus in the family bunyaviridae .\nit causes epizootic and sporadic outbreaks of abortions , premature births , stillbirths , and congenital abnormalities characterized by arthrogryposis , hydranencephaly , or microanencephaly in cattle , sheep , and goats .\nakav is widely distributed in the tropical and temperate zones in australia [ 3 , 4 ] , southeast asia , east asia [ 6 , 7 ] , the middle east , and africa .\nakav infection of adult cattle causes a transient viraemia without obvious clinical signs , while infection of pregnant cattle often causes fetal damage resulting in abortion , stillbirth , or various congenital abnormalities . during 1972 to 1975 , this disease had led to the birth of more than 42,000 abnormal calves in japan , causing significant economic loss in cattle industry [ 6 , 11 ] .\nsubsequently , major outbreaks resulting in congenital defects in ruminants caused by akav were reported from israel , australia , taiwan , korea , and turkey [ 7 , 10 , 1215 ] . in sudan ,\nakav infection was recognized based on serological evidence in sheep , goats , and cattle in various ecological zones of the country . the present study aimed at investigating the current situation of akav infection in sudan as a part of an ongoing research project on viral causes of reproductive problems of cattle in the country .\nthe investigation area extends from the latitudes 11 78 to 19 61 north and longitudes 22 45 to 37 21 east .\nsera were collected from dairy cattle in white nile , kassala , north kordofan , sennar , blue nile , north darfur , red sea , gadarf , khartoum , and gazira states .\n= 4pq / l , where n is the required number of individuals to be examined ; p is a known or estimated prevalence ; q = ( 1 p ) ; l is the allowable error .\nsince location to location variation was expected , the sample size was increased and all collected sera ( n = 361 ) were tested ( table 1 ) .\nblood samples were collected from 361 dairy cattle in 10 states of sudan ( table 1 ) .\nanimal sampled included individuals with history of abortion and infertility from two states , namely , khartoum and gazira states .\nanimals of both sexes and various age groups ( less than 6 months , less than 1 year , 1 - 2 years , 2 - 3 years , and more than 3 years ) ; breeds ( crossbred and indigenous ) under various management systems ( extensive , semi - intensive , and intensive ) and in different seasons including dry ( march june ) ; rainy ( july october ) , and winter ( november february ) were bled .\nsera were extracted by centrifugation at 1,500 rpm for 10 minutes and kept at 20c until they were tested for presence of antibodies against akav using elisa .\na total of 68 out of the 361 sera samples were collected from animals suffering from reproductive problems ( infertility and abortion ) .\ncommercial competitive elisa antibodies kit ( i d vet innovative diagnostics , france ) was used to detect antibodies ( anti - g1 ) against akav according to manufacturer 's instructions .\nthe serological results and other information gathered during this investigation such as locality , sex , season , management system , signs of reproductive problem , and breed ( indigenous and crossbred ) of the sampled animals were edited and analyzed statistically using statistical package ( spss version 16 ) . to identify the association of the risk factors with the specific seroprevalence , the chi - square ( test ) was used . the statistical significance level used was p 0.05 .\nthe overall prevalence rate of akav antibodies found in dairy cattle samples was 29.4% ( 106/361 ) ( table 1 ) . the prevalence rate varied from highest ( 69.6% ) ( 64/92 ) in khartoum state to lowest ( 3.3% ) ( 1/30 ) in sennar state .\nlikewise the prevalence of akav antibodies was significantly ( p < 0.001 ) higher in crossbred animals ( 39.9% ) than in indigenous breed animals ( 8.9% ) and in females ( 33% ) than in males ( 14.3% ; p < 0.001 ) .\nthe prevalence rates were significantly higher in intensively ( 37% ) managed animals ( p < 0.001 ) ( table 2 ) .\nthe seroprevalence was significantly high among 2 - 3 years old ( 45.3 ; p < 0.001 ) and in the winter season ( 58.1% ; p < 0.001 ) .\nthe prevalence rates were also high in cases of infertility ( 76.2% ) and abortion ( 48.9% ) when compared to apparently healthy animals ( 22.9% ) and were significantly associated with cases of infertility ( p < 0.03 ) ( table 3 ) .\nprevalence of akav antibodies in domestic ruminants in different ecological zones of sudan indicated prevalence rates of up to 27% in sheep , 36% in goats , and 47% in cattle .\nthe prevalence rates in cattle ranged between 10.6% and 47.8% in different areas . in the present study ,\nprevalence rates of akav antibodies in dairy cattle varied greatly ranging from 3.3% in sennar state to 69.6% in khartoum state with an overall prevalence rate of 29.4% .\nthis higher seroprevalence in khartoum state may be due to the fact that in this state 59 cattle sera out of 92 serum samples investigated were suffering from abortion ( 39 cases ) and infertility ( 20 cases ) ( table 3 ) .\nthis result confirmed records of jun et al . who discussed the associations between this virus and abortion suggesting that this virus may significantly increase abortion risk among cattle and sheep .\n. stated that transmission of akav in sudan may not be an annual event with more sporadic occurrences , a fact that may lead to variations in prevalence rates from year to year and from one area to another .\nthus , while these authors recorded a prevalence rate of 10.6% for sennar state , the prevalence recorded in the present study was 3.3% for the same area .\nhowever , both studies indicated wide geographic distribution of akav seropositivity in cattle in sudan indicating that the vector(s ) of aka virus are widespread ; unfortunately information regarding the vector(s ) in the country is lacking .\nit is interesting , however , that , inspite of the observed high prevalence and wide distribution of akav infection in sudan , no evidence of outbreaks of congenital malformations , as has been reported in other parts of the world , has been recorded in dairy cattle in sudan .\nthe present study also revealed that prevalence rates were highly associated with locality , breed , sex , season , age of animals , and management system .\nthe prevalence rate was significantly higher in khartoum state ( 69.6% ; p < 0.001 ) than in other states .\nanimals sampled in khartoum state were from intensively managed crossbred dairy cattle that reported reproductive problems based on a questionnaire survey administered prior to collection of samples in khartoum and in gazira states .\nthe prevalence rates were also significantly higher in crossbred animal ( 39.9% ; p < 0.001 ) than in indigenous ones ( 8.9% ) and in females ( 33% ; p < 0.001 ) than in males which may reflect higher degree of attractiveness of these animals to insect vectors .\nthe prevalence rates were also higher in intensive and semi - intensive management systems ( 37.0% and 36.1% , resp . ) than in extensive systems .\nthe previous two systems are generally concentrated around urban areas , and crossbred animals usually constitute the majority of animals in these systems while extensive systems are usually practiced in the vast grass lands of eastern and western sudan and usually involve indigenous animals .\nin addition vector arthropods may not be as numerous in the extensive system as in the intensive and semi - intensive system where microenvironmental conditions suitable for vector breeding and survival may be available year - round .\nseroprevalence rates were much higher in winter season ( 58.1% ) than in dry ( 25.6% ) or rainy ( 25.3% ) season .\nwinter season in much of the sudan is usually very mild with an average temperature that is usually above 30c .\nwhen examining prevalence rates of akav antibodies in individuals with reproductive problems , the results revealed that these rates were significantly higher in cases of infertility ( 76.2% ; p < 0.03 ) than in abortion cases ( 48.9% ) and were in both cases higher than in apparently healthy ( 22.9% ) animals .\nhowever , the high prevalence rates observed in both infertility and abortion cases may indicate the importance of akav infection in the bovine reproductive syndrome in sudan warranting further investigations .\nthe present study clearly indicated the widespread prevalence of akav infection in dairy cattle in sudan .\nabsence of clinically recognized symptoms of akav infections with noticeable outbreaks of abortion and foetal malformations may lead to underestimation of the importance of the disease in the sudan .\nthis situation may , however , change and the disease can pose considerable threat with the increasing trend toward intensive raising of exotic breed dairy cattle to satisfy the rising local demand for milk and other dairy products . hence , further countrywide epizootiological studies of akav infections in cattle , sheep , and goats are called for to provide information required for formulating well - designed control programs .", "answer": "a cross - sectional survey was carried out in ten states in sudan to determine seroprevalence and to assess risk factors associated with akabane virus ( akav ) infection in dairy herds . \n serum samples were collected from a total of 361 dairy cattle and tested for antibodies against akav using elisa . \n the prevalence rates of akav antibodies in cattle varied between 69.6% in khartoum state and 3.3% in sennar state with an overall prevalence rate of 29.4% . \n the prevalence rates of akav antibodies were significantly associated with breed being high in crossbred ( 39.9% ; p < 0.001 ) ; female sex ( 33% ; p < 0.001 ) , and animals in the age group of 2 - 3 years old ( 45.3% ; p < 0.001 ) . \n akabane virus antibodies prevalence was also highly associated with locality ( p < 0.001 ) ; season being high in winter season ( 58.1% ; p < 0.001 ) ; and animals raised under intensive management system ( 37% ; p < 0.001 ) . among 68 cases suffering from reproductive ( abortion and infertility ) problems the prevalence rate of akav antibodies in animals with infertility problem ( 76.2% ; p < \n 0.03 ) was significantly higher than in animals with abortion ( 48.9% ) . \n the study revealed that akav infection is highly prevalent in dairy cattle in sudan and this calls for control strategy to be implemented .", "id": 827} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfor repeated administration of chemotherapeutic agents , intravenous hydration , or parenteral nutrition to cancer patients or chronically ill patients , the role of the totally implantable central venous port ( ticvp ) system is greatly increasing to address concerns about quality of life . annually , more than 5 million central catheters are implanted in the us , and the proportion of implantable catheter systems has been increasing since niederhuber et al . first reported this system .\nsurgeons cut down or percutaneously puncture the cephalic , subclavian , or jugular vein , whereas interventional radiologists access the subclavian or jugular vein with the guidance of venography , ultrasound , or fluoroscopy .\nrecently , ultrasound - guided access to the vein , especially the internal jugular vein , and fluoroscope - guided positioning of the catheter have become widely accepted to reduce complications such as pneumothorax , pinch - off phenomenon , hematoma , or malposition of the catheter tip . however ,\nbecause thoracic surgeons are familiar with the percutaneous puncture technique , cut down insertion of the central catheter , and the anatomy of the chest and neck vasculature , they can detect complications and manage them promptly and accurately .\nthey can also create a pocket port easily , given their training in pacemaker pocket creation .\nin keimyung university dongsan medical center , the ticvp system has been provided by a thoracic surgeon since march 2009 .\nall of the procedures were performed with one small skin incision and subcutaneous puncture of a subclavian vein . in this article , we summarize our experience of the ticvp system and present the success and complication rate of this surgical method .\nthe purpose of this study is to determine whether implanting a ticvp system with surgical methods is as safe as performing it with radiologic guidance .\nbetween march 2009 and december 2010 , 245 port systems were implanted into 242 patients by thoracic surgeons .\nthe patients ' age , sex , underlying diseases , indications of the implantable port system , immediate and delayed complications , and total period of implantation of the port system were evaluated .\nall of the study protocols were accepted by the institutional review board of keimyung university dongsan medical center . before performing the procedure , the patient 's coagulation status including prothrombin time , activated partial thromboplastin time , and platelet count were checked .\nin the operating room , intravenous sedation was not performed and the patient was monitored with electrocardiography , pulse oximetry , and automatic cuff blood pressure . the neck and whole chest was prepared and draped .\na circulating nurse was positioned near the patient 's head and constantly checked the patient 's condition during the operation . as a port site ,\nhowever , if the patient had received mastectomy or radiation therapy on the right side , or had a previous port scar , the left anterior chest was chosen .\nafter subcutaneous injection of 1% lidocaine for local anesthesia , a 3 cm transverse incision was made just 2 cm distal to the lower margin of the clavicle at the deltopectoral groove level .\ngentle dissection of the subcutaneous tissue was done with electrocautery until the fascia layer was reached . at this layer ,\na pocket for the port was created with blunt and sharp dissection . to prevent skin tightness or necrosis , sufficient space for the port\nwas provided with minor bleeding control . after preparing the port site , an additional subcutaneous injection of lidocaine\nan introducer needle was inserted at the deltoid tuberosity level while gently withdrawing the plunger of the syringe . because the needle was inserted through previously dissected subcutaneous tissue , no additional incision was needed .\nthen the needle was inserted under and along the inferior border of the clavicle , making certain that the needle was virtually horizontal to the chest wall .\nonce under the clavicle , the needle was advanced toward the suprasternal notch until it entered the vein .\nwhen we failed infraclavicular subclavian vein access , we converted to a supraclavicular subclavian vein puncture just lateral to the sternocleidomastoid muscle ( fig .\n1 ) . after insertion of a j - tip wire , a groshong catheter ( bardport ; bard\n, salt lake , ut , usa ) was introduced through the peel off sheath .\nafter checking the venous return through the catheter and ensuring adequate heparinization , the catheter was cut to connect with the port ( bardport ) .\nthe catheter was inserted to a depth of 13 to 16 cm of the catheter length through the subcutaneous puncture site ( fig .\ntwo anchoring sutures between the port hole and subcutaneous tissue were made to fix the port .\nafter checking the patency of the port and flushing it with heparin , the wound was closed with tight obliteration of the dead space to prevent hematoma . after returning from the operating room ,\na routine chest x - ray was obtained to check the catheter position and to rule out postoperative complications like pneumothorax .\na series of 245 port systems were implanted into 242 patients , including 82 men and 160 women , with an age range of 14 to 86 years ( mean , 55.74 ) . in 240 of the patients ,\nthe ticvp system was implanted for chemotherapy and other oncologic management , while in 2 noncancerous patients , the system was implanted for parenteral nutrition or to secure an intravenous route .\nthe pocket sites for the port were created on the right side of the chest wall in 203cases ( 85.3% ) . in 42 cases ( 14.7% ) , the left side of the chest wall was used due to previous scarring or wound problems in 10 , right side mastectomy in 9 , the patient 's preference for the left side in 9 , failure of right side subclavian venous puncture in 4 , pain or edema in the right arm in 4 , and other reasons in 6 .\ntwo patients ( 0.82% ) underwent supraclavicular access of the subclavian vein after failure of infraclavicular access .\nsecondary insertion of the port system was performed in 6 patients , including 3 after it was surgically inserted with this method , 2 after radiology - guided insertion , and 1 inserted at another institution .\nthe mean operating time was 22.611.5 minutes ( range , 10 to 80 minutes ) .\naccidental arterial puncture occurred in some cases , but there was no hematoma or hemothorax occurrence .\nearly complications within 30 days of surgery occurred in 11 patients ( 4.49% ) , including malposition of the catheter tip in 6 , malfunction of the catheter in 3 , and port site infection in 2 . among patients who experienced malposition of the catheter tip\n, 2 were explanted , but the others refused to remove the catheter ( fig .\nthere was no evidence of venous thrombosis during their catheter indwelling . at the time of chart review ,\nlate complications occurred in 12 patients ( 4.90% ) including venous thrombosis in 4 , fever of unknown origin in 4 , skin necrosis in 3 , and sepsis in 1 patient .\nwe performed explantations in 25 patients ( 10.2% ) including 6 explantations after completion of chemotherapy . during explantation\ncompression of the puncture site for a while and complete obliteration of the port site dead space was performed .\nthe median duration of the ticvp system was 287.2 days , ranging from 3 to 980 days .\na totally implantable port system has been used increasingly since its introduction by niederhuber et al . .\nthe types of access vein and port site have varied according to the surgeon 's preference .\nwith cut down procedures , the cephalic vein or external jugular vein was preferred , while for percutaneous access , the subclavian or internal jugular vein approach was more frequently used . nowadays , to reduce perioperative complications and for accurate positioning of a catheter , ultrasound- , venography- , or fluoroscope - guided access\ninterventional radiologists prefer the sonographic approach using the internal jugular vein than the external landmark - guided technique [ 6 - 8 ] .\nsome surgeons prefer the cut down procedure to the cephalic vein instead of the percutaneous approach of the subclavian vein to avoid the risk of pneumothorax .\nhowever , for a long period of time , the subclavian vein has been a preferred route for placement of the central venous catheter .\nthis route provides a lower chance of infection and good stability on the chest wall . because the left innominate vein forms an acute angle from the vena cava , and has the possibility of damaging the thoracic duct , the right subclavian vein is preferred over the left .\npneumothorax occurs at a rate of 1% to 2.5% incidence after interventional radiologic placement of the chest port [ 6 - 8 ] , while occurring at an incidence of 2.4% to 4.3% after implantation by a surgeon .\nfound that there was no difference in early complications among the internal jugular , subclavian , and cephalic veins in their comparison of central venous insertion sites .\nthey also found that ultrasound - guided subclavian insertion showed the lowest proportion of failure .\nmeanwhile teichgraber et al . reported no incidence of pneumothorax after 3,160 cases with an ultrasound - guided internal jugular vein approach . in our study ,\nif surgeons are very familiar with chest and neck vasculature , and have good hands with subclavian vein access , the incidence of pneumothorax will decrease .\nin addition , if the needle should proceed toward the sternal notch slowly and directly without changing the axis , the chance of pneumothorax would be rare .\nhowever , the slow and gentle advance of the needle during venipuncture , accurate checking on the venous blood return to the syringe , and rapid withdrawal of the needle after puncturing the artery can prevent these events . in our experience , even after arterial puncture , rapid removal of the puncture needle and compression of the adjacent soft tissue for 1 or 2 minutes could prevent hematoma formation in every event . in early insertion periods ( march to may , 2009 ) ,\nwhen puncture through right subclavian access failed , the insertion site was changed to the left side . as a skin incision on the right anterior chest had already been made , an additional incision and pocket making was needed in the left side .\nsupraclavicular needle puncture to the subclavian vein just lateral to the sternocleidomastoid muscle was performed . with this route , the surgeon did not need to change the original patient 's right side position . when trying to access the internal jugular vein , the surgeon should change position to the patient 's head side .\ntwo operations ( 0.82% ) were performed and no occurrence of pneumothorax with this method was observed .\nlin et al . reported their experience using external jugular vein cut down , when the cephalic vein approach failed .\nbelow the cutdown site of the cephalic vein , they made a pocket for the port , where a new external jugular vein provided an excellent alternative route .\nfor secure and long - term maintenance of a ticvp system , the catheter tip position is crucial .\nthe united states food and drug administration has stated that the catheter tip should not be placed in or allowed to migrate into the heart . when the catheter is positioned in the right atrium\n, it may cause cardiac - related complications such as perforation , tamponade , arrhythmia , or cardiac thrombosis .\nfurthermore , catheter tips placed in the superior vena cava ( svc ) may cause port malfunction .\nmany authors agree with positioning the tip at the svc - right atrial junction . on standard chest radiograph , because the upper border of the svc is at the level of the inferior border of the clavicle , or the angle of the right main bronchus and trachea , the catheter tip should be located below this level .\nthe svc - right atrium junction level on chest radiograph is somewhat different according to different authors .\ndefalque and campbell have mentioned that the ideal tip position is between the fifth and sixth thoracic vertebrae , whereas rutherford et al\n. mentioned that it is between the right lateral margin of the svc and superior border of the cardiac silhouette , while another author described it as 1 cm inferior to the right superior cardiac border . with preliminary evaluation of the optimal catheter tip length under fluoroscopic guidance prior to the operation\n, we attempted to keep the catheter length 13 to 16 cm from the subcutaneous insertion site in the operative field .\nas our procedures were performed without radiologic guidance , we tried to keep the catheter tip from entering the svc area by a j - tip wire heading caudally , slowly proceeding the catheter , and checking cardiac ectopy on the monitor .\nhowever , we found a malpositioned catheter tip located in the internal jugular or contralateral innominate vein in 6 patients ( 2.45% ) .\nin this situation , we could have changed the tip position by the endovascular snaring technique or by reinsertion of the catheter in the operating room . but no patient wanted these procedures .\n1 ) since all of the procedures are performed in the operating room , the risk of infection will be lower than procedures done in the angiographic suite .\n2 ) because we form the pocket and perform subcutaneous cannulation of the catheter with one small skin incision , no additional incisions or subcutaneous tunneling is needed .\n3 ) because the implanted catheter length is short , the risk of catheter - associated complications like lumen occlusion and infection might decrease .\nhowever , since we did not perform a comparative study with a radiology assisted port insertion group , we have a limited ability to test these advantages . for a surgically implanted system using a subclavian vein , complication rates of 5% to 24.6%\nhave been reported and those radiologically implanted at the same site show a lower complication rate up to 20.7% .\nhowever , considering the high incidence of malposition of the catheter tip , complementary cooperation with a radiologist would be needed .\nsurgical insertion of a ticvp system with percutaneous subclavian venous access is a safe procedure with a lower complication rate and many clinical benefits .", "answer": "backgroundthe role of totally implantable central venous port ( ticvp ) system is increasing . implantation performed by radiologist with ultrasound - guided access of vein and fluoroscope - guided positioning of catheter \n is widely accepted nowadays . in this article \n , we summarized our experience of ticvp system by surgeon and present the success and complication rate of this surgical method.materials and methodsbetween march 2009 and december 2010 , 245 ports were implanted in 242 patients by surgeon . \n these procedures were performed with one small skin incision and subcutaneous puncture of subclavian vein . \n patient 's profiles , indications of port system , early and delayed complications , and implanted period were evaluated.resultsthere were 82 men and 160 women with mean age of 55.74 . port system was implanted on right chest in 203 , and left chest in 42 patients . \n there was no intraoperative complication . \n early complications occurred in 11 patients ( 4.49% ) including malposition of catheter tip in 6 , malfunction of catheter in 3 , and port site infection in 2 . \n late complication occurred in 12 patients ( 4.90%).conclusionsurgical insertion of ticvp system with percutaneous subclavian venous access is safe procedures with lower complications . \n careful insertion of system and skilled management would decrease complication incidence .", "id": 828} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncongenital ptosis is an abnormally low position of the upper eyelid in relation to the globe , which occurs either at birth or soon after .\nthere are several methods of ptosis surgery , including levator muscle resection , frontalis suspension procedure , fasanella - servat procedure , and mller muscle \nconjunctival resection.1,2 one of the most popular methods of ptosis surgery is the frontalis suspension procedure .\nthere are various materials available to secure the lids to the frontalis muscles in the frontalis suspension procedure , including polypropylene suture , nylon suture , silicone , mersilene mesh , and gore - tex material.3 we are reporting a rare case of infected gore - tex material that was used in modified frontalis sling surgery for congenital ptosis .\na 7-year - old chinese boy with no known medical history , presented with history of right eye ptosis since he was 10 months old .\nhe had a marginal reflex distance of 1 mm , with levator function of 3 mm in the right eye .\nthe marginal reflex distance of the left eye was 2 mm , with 7 mm levator function .\nhe underwent ptosis surgery on the right eye as he developed mild amblyopia in the right eye , with the best - corrected vision of 6/12 . a right eye frontalis sling procedure with modified fox s pentagon method4\nchloramphenicol ointment was applied 8-hourly to the surgical wound site on the right upper eyelid .\nthe patient was discharged on day 1 postoperation , with plan to review after 1 week .\nhowever , he defaulted his follow - up and only came back 1 month after surgery .\nhe had used his medication for only 1 week and had stopped thereafter . at this presentation , he complained of painful swelling ( of 7 days duration ) of the right upper eyelid .\nthe right upper eyelid swelling was associated with pus discharge from the surgical wound site .\nhis best - corrected visual acuity was 6/12 in the right eye and 6/9 in the left eye .\nthere was presence of crusted pus at the surgical wound site ( figure 1 ) .\na diagnosis of right eye preseptal abscess secondary to the infected surgical wound was made .\nthe patient was admitted and treated with intravenous co - amoxiclav 800 mg ( 25 mg / kg ) 8-hourly for a duration of 1 week .\nchloramphenicol ointment was applied 8-hourly to the infected surgical wounds , together with instillation of topical chloramphenicol eye drops 6-hourly to the right eye . an emergency incision and drainage of the right upper eyelid was performed , and about 5 ml of pus was drained out .\npost - incision and drainage , the right upper eyelid was still inflamed and swollen with partial mechanical ptosis ( figure 2 ) . in view of no improvement in the healing process ,\nthe antibiotic was changed to intravenous cefotaxime 750 mg ( 25 mg / kg ) 8-hourly for a duration of 1 week .\nthe topical antibiotic eye drop was also changed to topical moxifloxacin 6-hourly for the right eye .\nhowever , there was still no improvement ; hence an antibiotic combination of intravenous ceftazidime 750 mg ( 25 mg / kg ) 8-hourly for 5 days and intravenous amikacin 210 mg ( 15 mg / kg ) 12-hourly for 3 days was commenced .\na third incision and drainage was performed together with removal of the gore - tex material . a culture from the final pus sample isolated multidrug - resistant acinetobacter species , which was resistant to all penicillins , cephalosporins , carbapenems , fluoroquinolones , and aminoglycosides\nthere was resolution of the right upper eyelid swelling , with no more pus discharge .\nthe patient was discharged , with chloramphenicol ointment to apply to the surgical wound 8-hourly for 2 weeks .\nafter 6 months follow - up ( about 3 months post - removal of gore - tex material ) , the patient s right upper eyelid was healed with scarring , but without ptosis ( figure 3 ) .\nfrontalis suspension surgery is a commonly used surgery in cases of congenital ptosis with poor levator function , chronic progressive ophthalmoplegia ( cpeo ) , muscular dystrophy , third nerve palsy , myasthenia gravis , and aponeurotic ptosis in elderly patients.1,3 there are several suspension materials that can be used in frontalis suspension surgery .\nsynthetic materials such as polypropylene suture , nylon suture , silicone , mersilene mesh , and gore - tex can also be used.5 gore - tex material or expanded polytetrafluoroethylene ( eptfe ) is suitable for suspension surgery because it is less bulky and less stretchable.5 it is a nontoxic polymer used in various other implantable medical products , including vascular grafts and hernia repair patches . unlike other implantable materials , eptfe is biocompatible .\nmicropores within the material are too small to allow infiltration of fibrovascular tissues hence allowing for easier removal or manipulation to adjust the eyelid height.6,7 however , its porous nature may allow proliferation of bacterial contaminants and cause abscess formation , resulting in a high risk of soft tissue complications . in our patient , constant\nscratching may have led to infection of the wound . with tracking of the long , porous eptfe material through an open wound\nthe periorbital abscess was chronic and persistent even after treatment with multiple antibiotics and repeated incision and drainage , indicating the highly virulent nature of the causative organism .\nthis could be due to the formation of biofilm by the causative bacteria , especially on biomedical implants , causing antimicrobial resistance.8 complete resolution in our case occurred only after removal of the gore - tex material , which might have harbored the virulent microorganism .\nthere were a few other reports of complications of ptosis surgery such as granuloma and infection.2,3,9 in a retrospective study of 59 frontalis suspension procedures , infection with preseptal cellulitis appeared in one case ( 1.7% ) and required removal of the material , and in two cases ( 3.4% ) there were foreign body granulomas that were resolved by excision.10 there were other reports of post - ptosis surgery complicated by long - standing postoperative infection which were mostly associated with mycobacterium or candida infection.11,12 however , to our knowledge , there was no reported case of long - standing post - ptosis surgery infection involving multidrug - resistant acinetobacter species .\nacinetobacter rarely colonizes implant materials;13 it commonly causes nosocomial infections such as pneumonia , urinary tract infection , and skin infections.14,15 in a delayed and long - standing post - frontalis surgery infection , multidrug - resistant organisms may be responsible for delayed healing and poor response to treatment .\nsurgical removal of infected slings and a prolonged course of antibiotics may be required for complete resolution .", "answer": "a 7-year - old boy had a case of congenital ptosis of the right eye and has undergone frontalis sling surgery using gore - tex material . \n there was no intraoperative or immediate postoperative complication . \n however , the patient defaulted his follow - up and presented with right eye preseptal abscess secondary to infected surgical wound 1 month after surgery . \n he was treated with multiple antibiotics and underwent repeated incision and drainage procedures . \n however , there was still no resolution of the right eye preseptal abscess . \n the patient s condition subsequently improved after removal of the gore - tex material and treatment with an antibiotic combination of ceftazidime and amikacin . \n microbiological analysis finally isolated the multidrug resistant acinetobacter species . at 6 months \n follow - up , his right upper eyelid was healed with scarring , but without ptosis .", "id": 829} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynthetic in vitro circuits\n\nPaper sections:\nIntroduction\nBreakthroughs in our ability to read and write DNA have enabled researchers to construct sophisticated, circuit-like behavior in living systems [1]. More than ten years ago, pioneering efforts by Elowitz and Leibler and Gardner et al. [2,3] provided a conceptual framework for viewing cells as a system of interacting circuits \u2013 structures composed of several elements that are capable of information processing by accepting an input, executing a series of logical computations, and producing an output. This framework, championed by many synthetic biologists [4], has inspired new applications and shed light on our understanding of fundamental biological phenomena. Nevertheless, in vivo circuitry is often unpredictable. Even if the functions of individual `parts' are known, they may not work as expected in different cellular contexts due to intertwined circuit dependencies and crosstalk between biomolecules. Thus, the complexity of successfully implemented in vivo circuits to date is limited in size and scope to tens of molecules [4]. This pales vastly in comparison to the simplest living organisms, which consist of several hundred to thousands of genes, non-coding RNA species, and small molecules.
As a complement to in vivo-based approaches, in vitro systems provide an unprecedented freedom to modify and control biochemical systems for technological applications and to understand the design principles of biological circuits. Removing genetic regulation, for instance, drastically reduces complexity by negating a cells' ability to adapt and evolve [5]. For decades, in vitro systems have made integral contributions to biological research in both discovery and technology - from discovery of the genetic code [6] to the development of core techniques such as the Polymerase Chain Reaction [7] as well as disruptive technologies for manufacturing-scale cell-free protein synthesis [8]. Now, the study of complex biological circuits is emerging as a novel application of in vitro systems that can complement and guide in vivo studies.
This review will focus on recent developments in the field of synthetic in vitro circuits over the last 3 years. We first examine minimal nucleic-acid based systems that offer unparalleled experimental flexibility and predictability. Next, we discuss circuits created in hybrid systems \u2013 containing purified enzymes and nucleic acids. We end our discussion of in vitro circuits on complex systems that are capable of transcription and translation.
\n\nNucleic acid systems\nWhile the classical sense of the word \"circuit\" conjures up images electricity flowing through transistors, DNA is capable of both carrying information and performing computations on that information [9,10]. Circuits constructed in this manner have relatively few possible interactions and points of control (Figure 1\n(top)) making their quantitative description more manageable and comprehensive. They provide theoretical insight into the generalized function of chemical circuits based on diffusion and stochastic binding \u2013 principles that must be understood to make genetic circuit design a predictive science.
Dramatic increases in circuit complexity in DNA systems over the last three years partly stem from the development of `seesaw' gates that make use of toehold exchange reactions (Figure 2A,B) [11\u201313\u2022\u2022]. In classical toehold displacement reactions, a single-stranded DNA (ssDNA) molecule displaces one strand of a double-stranded DNA (dsDNA) complex by binding to a complementary short overhang (toehold) region on the dsDNA. The ssDNA (input) displaces the previously bound strand of DNA (output), which can then serve as an incoming signal for another reaction. From this starting point, researchers have built a diversity of nano-scale devices and circuits capable of complex computation (see [14\u2022] and [15] for more comprehensive reviews).
In the case of toehold exchange reactions, the reverse reaction is made possible by including a toehold design on both sides of the dsDNA molecule (Figure 2A). Only two cascaded seesaw gates are required to produce the OR and AND logical functions (Figure 2B) and more complex cascades can compute NOT, NAND, NOR, and XOR. To show the scalability of these gate units, Qian et al. constructed a neural network consisting of 112 DNA strands that demonstrates associative memory capable of answering 81 possible questions [16], as well as a 130-stranded DNA circuit capable of computing the square root of a 4 digit binary number [17\u2022].
Models derived from experimental investigations [11,12] are increasingly accurate at predicting the kinetics of strand displacement reactions and have allowed construction of increasingly complex implementations. Further, experiments guided by thermodynamic models have verified designs that perform within a 20\u00b0C range of temperatures, 1\u20135 \u03bcM concentrations of nucleic acid, and 1\u201347 mM Mg2+ [18\u2022]. This robustness illustrates that the understanding gained from these systems may be generalized to a range of conditions and not limited to particular experimental set-ups. A suite of computational tools, theoretical frameworks and even dedicated programming languages can be used to design and analyze DNA circuits [19\u201323]. Concurrently, novel theoretical possibilities [24] and practical implementations are continually being developed such as those utilizing hairpins [25,26], cooperative binding [27], deoxyribozymes [28,29], photochemical activation [30] and associative toehold activation [31].
Importantly, studying strand displacement circuits in vitro has led to practical uses that would have been difficult to anticipate prior to the expansion of this largely theoretically motivated work. Researchers have shown that in vitro DNA circuits can amplify signals and detect RNA and small molecule analytes using different reporting methods [32]. Further, an area of research that is likely to expand involves using DNA circuits as visualization tools for imaging DNA based reaction cascades [33], mRNA's [34] and reversibly imaging proteins [35].
\n\nHybrid systems\nUnderstanding and exploiting transcriptional logic is a complex problem that unites many fields of biology, but the vast number of interacting species and circuit cross talk within cells makes it difficult to characterize individual transcriptional gates. In vitro hybrid systems composed of DNA templates and purified enzymes, however, allow researchers to isolate the performance of small circuits before exploring how they interact within larger biochemical systems [36\u201339]. DNA still acts as the logic gate for signal integration (see Figure 3A for sample AND gate implementation), but the inputs and outputs can be DNA, RNA, or metabolites.
Hybrid systems are able to amplify signals, produce new signals, and degrade waste products \u2013 functionality that is difficult to implement in nucleic acid systems. Pioneering studies in 2011 highlight the diversity of these circuits, and the fact that similar high-level designs can be implemented in different ways. Montagne et al. created a system (the \"Oligator\") capable of sustained oscillations using DNA polymerase, a nicking enzyme, and an exonuclease that were responsible for amplification, propagation, and destruction of information carrying DNA oligonucleotides [40\u2022\u2022]. This circuitry used only three template strands and three enzymes but was able to couple a positive feedback and a delayed negative feedback loop in a computationally predictable manner that used readily attainable parameters.
Using a different molecular implementation, Kim and Winfree produced a system capable of sustained oscillations by using RNA polymerase and RNaseH to produce and degrade cascading DNA/RNA signals [41\u2022\u2022]. They showed oscillations using three distinct designs: a seven-stranded two-switch negative feedback oscillator, an amplified negative feedback oscillator which included the use of a positive feedback system, and finally a novel molecular implementation of a three-switch ring oscillator that was the focus of pioneering in vivo studies [2]. Franco et al. later expanded on this oscillating system and displayed potential applications by using the negative feedback oscillator as a timing device to separately activate DNA nanotweezers and produce an RNA aptamer [42\u2022\u2022]. As with Montagne et al., modeling was integral to understanding system behavior and parameters \u2013 including concentrations and sequences \u2013 that would produce desired results. Merely by introducing the novel interaction that was required to time their device, the oscillations were severely restricted compared to the original system. This problem of coupling distinct systems was elegantly overcome through the use of an insulator circuit that isolated the output signal and prevented it from disrupting the timing device.
While the previous studies showed successful implementations of designs, they varied in their predictability and quantitative understanding of the systems. Deviations from kinetic models, especially with regards to the repressilator implementation, highlight the shortcoming of our knowledge and make a strong case for studying these systems before attempting to explain more complex cellular oscillators. For instance, incomplete degradation products may partially inhibit reactions in ways that are difficult to predict. In addition, small differences in transcription and degradation rates can compound over time and result in unstable oscillations with growing amplitudes or mono-stable behavior. Nevertheless, studies aimed at predicting and modeling more complex systems show a clear path forward for creating autoregulatory switches [43], neural networks [44], incoherent feed forward loops [45], pattern formation reactions [46\u2022], as well as transcriptional rate regulation based on self-repression [47] and positive feedback [48].
As with DNA circuits, hybrid circuits have a variety of potential applications that are just beginning to emerge. In work that stems partly from initial theoretical and in vitro research[49], hybrid circuits were demonstrated inside Drosophila embryo lysates [50] providing insight on the functioning of circuits in a much more complex chemical environment. Several studies showed successful in vivo implementations of logical computing for potential applications in diagnosis and therapeutics [51,52].
\n\nComplete systems\nAlthough previously mentioned studies may include the use of proteins, complete (either purified, or extract based) systems produce proteins in vitro and integrate them into circuits. Logical integration occurs at the DNA level but inputs and outputs may be DNA, RNA, protein, or metabolites \u2013 all of which may be produced, degraded, or modified in response to signals. Importantly, the diversity of interactions means that there are many more steps that must be understood for predictive implementation of complex circuits (Figure 1). However, these extra steps are also novel points of control that, once thoroughly characterized, may be exploited by researchers to construct highly complex logic systems.
Complete cell-free circuits began with the seminal work in 2003 of Noireaux et al. who showed that activating and inhibitory proteins could be produced in vitro and that one-, two-, and three-stage cascades could be created using these proteins as circuit elements [53]. Rather than relying on orthogonal promoters from these previous studies, Shin and Noireaux have recently recreated [54] and comprehensively characterized the endogenous sigma factor-based regulation system for use in Escherichia coli extracts [55\u2022\u2022]. This allowed for the construction of the logical AND gate (Figure 3B), negative feedback loops, and multiple stage cascades. They also demonstrated the modularity of their toolkit for future applications of in vitro metabolic engineering and as a possible testing ground for in vivo recombinant circuit design. In complementary work, Asahara and Chong expressed promoter subunits and sigma factors in a single tube and showed promoter specific transcription initiation from solely in vitro translated and assembled products [56]. Taking an alternative route towards a similar goal, Karig et al. expanded on the original work of Noireaux et al. by showing that tool-kits based on orthogonal T7 promoters are capable of complex computations by characterizing several inducible and repressible variants and creating a negative feedback loop in vitro [57].
An overarching theme of these studies is the precise characterization of individual circuit elements, which are then implemented into complex cascades where their interactions may be controlled. While the search for biological `parts' has proven fruitful for in vivo synthetic biologists, many of these parts are still highly context dependent. In cell-free systems, these parts exist in a context outside of cellular adaptation and evolution and the results are therefore expected to be more tunable and reproducible. However, before controlling protein levels based on logic integration, we must understand the range of possible points of control and parameters that are important to steady-state protein levels. Karig et al. looked at the effects of ribosome binding sites and plasmid usage on target protein levels that were essential components of their circuit [57]. Though they did not explicitly recreate circuits, in separate studies Ahn et al. used cell-free systems to characterize the effects of 3' transcript stability, fusion partner leader sequences, and initial codons on protein production rate and steady state levels [58\u201360]. Many of these studies look at determinants of single protein production, but Du et al. have taken this work one step farther and studied the complications that arise when trying to express multiple proteins in vitro [61]. Karzbrun et al. took a step towards integrating the effects of these different components by creating a computational framework for predicting protein levels [62\u2022]. With this knowledge, researchers may be able to implement logical control at specific processes to enable diverse circuit designs and some even dream of minimal cells [63].
Finally, in what we believe will be an increasing trend during the coming years, several studies have designed and analyzed circuits in vitro and successfully implemented those designs in vivo. Saito et al. developed a translational regulatory system based on L7Ae, an archael ribosomal protein, binding to mRNA molecules [64\u2022\u2022]. They describe different mRNAs that are capable of activation and repression in response to the same protein input. This elegant study highlights the diversity of possible inputs that can be accepted by circuits composed in complete systems and exploits a unique control point that is only available in systems capable of translation. Importantly, their design was first tested in a purified cell-free translational system before being successfully implemented inside of a human cell-line. Similarly, Karig et al. tested their T7-driven negative feedback constructs in a purified cell-free translation system, cell extracts, and E. coli cells and showed the expected functionality across all systems [57]. These studies indicate that in addition to an increasing number of in vitro applications [65,66], in vitro environments can be a training ground for in vivo circuit design.
\n\nConclusion\nThere has been dramatic growth in the construction, complexity, and predictability of cell-free biological circuits over the past three years. This growth underscores the importance of cell-free systems as a novel environment for engineering and analyzing complex biological circuits at the molecular level. In addition, designs that rely on DNA strand displacement reactions are yielding tremendous insight into the emergent behavior of complex chemical systems that lies at the heart of cellular life. Recent growth in this field also reflects an increasing interest in exploiting the unprecedented freedom of design afforded by cell-free biology for compelling applications [5,65\u201367]. The in vitro circuits described above, being structurally and functionally diverse, are poised to impact chemical, physical, biological, and computational research in diverse and unpredictable ways. This is precisely what makes their continued development necessary and exciting.
", "answer": "Inspired by advances in the ability to construct programmable circuits in living organisms, in vitro circuits are emerging as a viable platform for designing, understanding, and exploiting dynamic biochemical circuitry. In vitro systems allow researchers to directly access and manipulate biomolecular parts without the unwieldy complexity and intertwined dependencies that often exist in vivo. Experimental and computational foundations in DNA, DNA/RNA, and DNA/RNA/protein based circuitry have given rise to systems with more than 100 programmed molecular constituents. Functionally, they have diverse capabilities including: complex mathematical calculations, associative memory tasks, and sensing of small molecules. Progress in this field is showing that cell-free synthetic biology is a versatile training ground for understanding native biological circuits and engineering novel functionality.", "id": 830} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary amenorrhea is usually the result of a genetic or anatomic abnormality . in young women with primary amenorrhea ,\nit is commonly caused by x - chromosome aberrations such as in turner syndrome , but individuals with a normal chromosome complement and ovarian dysgenesis also exist .\na 35-year - old female patient presented to our medical outpatient department with complaints of palpitation and chest pain of 6 months duration .\npatient had paroxysmal episodes of palpitations that lasted few minutes , resolved spontaneously , and were not associated with exertion or other aggravating factors . patient had chest pain that was retro - sternal , intermittent not related to exertion and resolved spontaneously .\nmenstrual history revealed that she never attained menarche . on examination she had dolicocephaly , arachnodactyly , high arched palate , she was tall statured [ height 165 cm ; figure 1 ] , her arm span ( 176 cm ) was more than her height , arachnodactyly [ figure 2 ] , reduced upper to lower body segment ratio ( 0.83 ) , and she had positive wrist and thumb sign .\npatient had underdeveloped rudimentary breasts ( tanner stage 2 ) , sparse pubic hair ( tanner stage 1 ) , and absent axillary hair .\ncardiovascular examination revealed mid - systolic click with a late systolic murmur , other systems were essentially normal .\nher blood glucose , renal function tests , liver function tests , and serum electrolytes were within normal limits .\nechocardiogram echo / doppler revealed prolapse of anterior mitral leaflet , mitral regurgitation and normal left ventricular systolic function .\nshe had low levels of estrogen ( estradiol-10 pg / ml ; normal 15 - 200 pg / ml ) , serum testosterone ( 0.16 pg / ml , normal 0.6 - 6.8 pg / ml ) , and progesterone ( 0.56 ng / ml ) . she had elevated levels of gonodotropins , follicle - stimulating hormone ( fsh ) ( 101.3\nserum prolactin ( 12 ng / ml , normal 0 - 20 ng / ml ) and thyroid function tests ( free t4 - 9.2 mcg / dl , normal 4.6 to 11.2 mcg / dl ; tsh-3.49mu / l , normal 0.4 - 5.0\nmarfanoid habitus : tall stature , height 165 cm ; arm span to height ratio of 1.067 ; upper segment to lower segment ratio of 0.83 arachnodactyly with high metacarpal index mci list of investigations that contributed in diagnoses of primary amenorrhea\nperrault and his colleagues in 1951 published the first report on two sisters with gonadal dysgenesis and with additional sensorineural deafness .\nhypothesized that there is a form of ovarian dysgenesis that is inherited as an autosomal recessive , female - limited disorder .\nneurologic data are available on 14 of 21 girls ; 7 of 14 had neurologic abnormalities .\nthey concluded that high incidence of neurologic anomalies suggest that ataxia or mental retardation may not be just coincidental findings , but pleiotropic manifestations of perrault syndrome .\nreported on two sporadic and two familial new cases with sensorineural hearing impairment and ovarian dysgenesis , which are the cardinal signs of perrault syndrome in females .\nreported on two pairs of sisters with gonadal dysgenesis and deafness , cerebral , and ocular involvement who developed a progressive , severe sensory , and motor neuropathy .\nbased on the clinical observations of known patients ; two forms of ps may be distinguished : one apparently non - progressive form and another with apparently progressive axonal - cerebellar degeneration .\nnishi et al . reviewed 21 patients from the literature , added ataxic gait , pes equinovarus , nystagmus , limited extraocular movements to the spectrum of neurologic defects in ps .\nabsence of deafness in a patient with xx female gonadal dysgenesis ( xx - gd ) does not rule out perrault syndrome because the patients could develop deafness much later , at an older age .\nmost patients had moderate to severe sensorineural deafness with mutism among patients with early onset of deafness .\nthe findings of abnormal body proportions noted in our patients have been previously reported by jacob et al . in their observation of two siblings with perrault syndrome with marfanoid habitus . the pathogenetic basis for the ps is still unclear .\nstudied a small family of mixed european ancestry includes two sisters with well - characterized perrault syndrome .\nwhole - exome sequencing of genomic dna from one of these sisters revealed exactly one gene with two rare functional variants : hsd17b4 .\nfurther studies on other families are awaited to confirm the homogeneity of the genetic defect and the underlying molecular defect .\nthese issues were discussed with our patient . during the follow up visits , we noticed depression and suicidal tendencies .\nafter a comprehensive psychiatric evaluation , she was diagnosed with major depression and was put on anti - depressant medication .\nwe did not advice any therapy for mitral valve prolapse as the prognosis in asymptomatic patients with nonsustained arrhythmias and structurally normal hearts is quite good .\nthus , the potential deleterious effects of drug therapy probably outweigh any risk from the arrhythmia in this setting .\nsimilarly , no antibiotic prophylaxis or anti - thrombotic prophylaxis was suggested as present guidelines recommends endocarditis prophylaxis for patients only at the highest risk .\nperrault syndrome is a rare cause of primary amenorrhea or ovarian dysgenesis , but should be considered in a female child with deafness / mutism .\nseveral reported cases have some form of neurologic deficit but our patient did not have any obvious neurological signs or symptoms , but she had marfanoid habitus , an association that was described only once in the literature .\nthe marfanoid features could be considered as a part of extended phenotype of perrault syndrome .", "answer": "gonadal ( ovarian ) dysgenesis with normal chromosomes ( 46 , xx ) , xx female gonadal dysgenesis ( xx - gd ) is a rare genetically heterogeneous disorder . in 1951 , perrault reported the association of gonadal dysgenesis and deafness , now referred to as perrault 's syndrome . \n perrault syndrome is a rare autosomal recessive condition affecting both females and males ; only females have gonadal dysgenesis associated with sensorineural deafness , which is present in both sexes . \n we present a case of sporadic perrault syndrome in a 35-year - old female with primary amenorrhea , sensorineural deafness , marfanoid features and normal karyotype . \n there are very few case reports describing the condition , even lesser reports of association with marfanoid habitus . \n we report this case for its rarity and add to the spectrum of the disease that remains undetermined .", "id": 831} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhyperthyroidism is commonly associated with atrial fibrillation ( af ) , particularly in the elderly .\nwe hereby report a case of patient with primary hypothyroidism presenting with af and pericardial effusion which resolved with levothyroxine therapy .\nhe complained of chest pain which was substernal , nonradiating , and throbbing in nature .\nhe smoked 10 cigarettes per day for past 25 years , and denied use of alcohol , caffeine , or drugs .\nphysical examination was unremarkable except for the irregular heart rate ( approximately 130 beats per min ) and muffled heart sounds on auscultation .\nelectrocardiogram [ figure 1 ] confirmed af with rapid ventricular rate , which responded to initial treatment with metoprolol [ figure 2 ] .\naf with rapid ventricular rate normalization of af with metoprolol thyroid function tests revealed a sensitive thyroid stimulating hormone ( tsh ) concentration of 34.70 iu / ml ( normal : 0.40 - 4.70 iu / ml ) , and thyroxine ( t4 ) of 5.57 g / dl ( normal : 8 - 12 g / dl ) confirming primary hypothyroidism .\ntransthoracic echocardiography showed normal left ventricular systolic function ( ejection fraction of 63% ) , decreased left ventricular diastolic compliance , and massive pericardial effusion ( posterior 17 mm , anterior 13 mm ) .\nright atrial and right ventricle showed 30% collapse during diastole , mild left ventricular hypertrophy was present with no regional wall motion abnormalities .\npatient was treated with levothyroxine which lead to resolution of symptoms and restoration of normal sinus rhythm .\nrepeat echocardiography showed no collapse of right atrium and right ventricle during diastole ) and mild pericardial effusion ( 11 mm circumferential ) .\nthe most common cardiovascular signs and symptoms of hypothyroidism include bradycardia , mild hypertension ( diastolic ) , narrow pulse pressure , cold intolerance , pericardial effusion , cardiomyopathy and fatigue .\nhypothyroidism is often associated with electrocardiographic changes like bradycardia , right bundle branch block , flat or inverted t wave , qrs prolongation , qt prolongation , and infrequently ventricular arrhythmia , torsades de pointes .\ntreatment of hypothyroidism is well - documented to cause af due to inadvertent overdosing of levothyroxine .\nalthough atrial arrhythmias are common and ventricular ectopy is rare in patients with hyperthyroidism , it is rarely associated with hypothyroidism .\naf is seen in 5 - 15% patients of hyperthyroidism and may be the presenting feature . increased chronotrophic activity\ndue to increased thyroid hormones and increased sympathetic tone are the proposed underlying mechanisms . the physiological chronotropic response and normal tension of the heart muscle in\ndiastolic phase depend on the action of triiodothyronine in the heart cells and its stimulating influence on na - k atpase and ca atpase in endoplasmic reticulum .\nnormal contractility is also related to triiodothyronine stimulated transcription of the myosin heavy - chain alpha gene and inhibition of the heavy - chain beta gene .\nmoreover , triiodothyronine acts on the cardiac muscle affects the number of beta adrenergic receptors and their sensitivity to catecholamines .\nfew case reports have demonstrated that hypothyroidism may cause a prolongation of the qt interval which predisposes the patient to ventricular irritability .\nthe canadian registry of atrial fibrillation investigators reported that 1.5% of 726 patients with af had hypothyroidism over a period of 1.7 years .\nstudies have also reported that up to 8% of patients with atrial fibrillation were hypothyroid .\nhypothyroidism is known to cause nodal defects , but the mechanism of af in hypothyroidism is not known .\nit is also not clear whether its presence is causally related or is a mere manifestation of an underlying unrecognized structural heart disease .\nhowever in our case , reversal of af with levothyroxine treatment negates underlying structural damage of the heart nans suggests causal relationship .\nprevious case reports have shown association of af with hypothyroidism but pericardial effusion was absent in those cases .\nthis is possibly the first reported case of af and pericardial effusion in a case of hypothyroidism .\nyoung patients with no evidence of organic heart disease may be started on a full replacement dose of thyroxine .\nolder patients or those with known or suspected ischemic heart disease , should initially be given about 25% of the anticipated replacement dose , and the dose should be increased gradually at 6 - 8 week intervals .", "answer": "a 72-year - old man presented with palpitation , dyspnea , and chest discomfort . \n initial investigations revealed atrial fibrillation ( af ) and pericardial effusion , further investigations unraveled primary hypothyroidism ( thyroid stimulating hormone ) of 34.7 iu / ml and total thyroxine ( t4 ) of 5.57 g / dl ) . \n treatment with levothyroxine led to resolution of symptoms , af , and pericardial effusion .", "id": 832} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nextraskeletal soft tissue chondroma is a very rare , slow - progressing , benign tumour .\nchondromas are tumour - like masses formed by proliferation of chondrocytes in a mature hyaline matrix .\na 22-year - male came with chief complaints of asymptomatic swelling on the palate since birth .\nhe had symptoms of cleft palate , i.e. , nasal regurgitation and poor speech . on examination\n, there was a complete cleft of secondary palate and the cleft was filled by non - tender , globular swelling of size 3 sq .\nthere was a linear band of soft tissue extending from the anterior part of the swelling to the upper lip mucosal surface after passing through the diastasis of the upper central incisors [ figure 1 ] .\npre - operative photograph showing palatal swelling completely obliterating the cleft with linear band extending to the lip on computed tomography scan , a 30 mm 28 mm size , well - defined , globular soft tissue mass was seen in the region of the hard palate , which showed fusion defect anteriorly .\nplain computed tomography coronal section of the swelling differential diagnosis of dermoid cyst and chondroma were kept .\nintraoperatively , the tumour was seen attached by a small pedicle to the nasal mucosa of the cleft margin on the right side .\nthe tumour was excised along with the linear band of tissue extending to the mucosal surface of the upper lip [ figure 3 ] .\nhistopathological examination revealed hypercellular lobules of cartilage composed of evenly spaced chondrocytes of uniform size and separated by collagen and adipose tissue .\nthere was no recurrence after 2 years of follow - up [ figure 5 ] .\nhistopathological appearance of the chondroma two - year follow - up photograph showing repaired palate having adequate length with no recurrence\nsoft tissue chondromas are benign cartilage - forming tumours that are usually found in close proximity to the tendon or joint capsules .\nonly five cases of soft tissue chondroma of palate have been reported in the literature.[36 ] it has never been reported in a patient of cleft palate .\none theory is that these lesions are from residual embryonal tissue ( embryonic remnant theory ) .\nthe other theory is that these lesions are from metaplasia of pluripotential mesenchymal cells ( metaplastic theory ) . in our case , because the swelling was present since birth , this goes in favour of embryonic remnant theory . even after a meticulous review of the literature , we could not establish the cause and effect relationship between chondroma and cleft palate .\nin fact , we feel that the embryonic changes in the palate during the process of cleft might lead to entrapment of mesodermal tissue ( mesoderm giving rise to cartilage / bone ) .\nclinically , these tumors present as slow - growing , firm masses not attached to the underlying bone and are , occasionally , painful .\nradiologically , soft tissue chondroma show well - demarcated , extraskeletal , soft tissue masses .", "answer": "soft tissue chondroma of palate is very rare . \n it has never been reported in a cleft palate patient . \n we report a case of 22-year - old male who came with asymptomatic swelling on the palate since birth , along with complete cleft of secondary palate . \n he had symptoms related to cleft palate only , i.e. , nasal regurgitation and speech abnormalities . \n swelling was excised and the cleft palate was repaired . \n histopathological examination revealed chondroma of the palate . \n the patient had no recurrence after 2 years of follow - up .", "id": 833} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntakotsubo cardiomyopathy , or transient apical ballooning syndrome , is a non - ischemic cardiomyopathy that mimics the onset of an acute myocardial infarction .\nits incidence was recently reported to be 1.72.2% among patients presenting with acute coronary syndrome .\ntakotsubo is also called broken heart syndrome because a strong emotional psychological stress may act as a potential trigger .\noriginally described in japan in 1990 , its eponym was coined using the two japanese terms tako ( octopus ) and tsubo ( pot ) , due to the resemblance between the cardiac apical ballooning ( hallmark of the syndrome ) and the octopus trap ( a kind of ceramic pot ) used by japanese fishermen .\nthe acute functional and instrumental abnormalities accompanying takotsubo cardiomyopathy occur in the absence of significant coronary alterations , and could be completely recovered within a few weeks up to two months . if promptly recognized and correctly managed , despite the severity of its onset and the potentially life - threatening characteristics ( those of a cardiogenic shock ) , this syndrome normally presents a good prognosis with low morbidity and in - hospital mortality rates , , .\nthis paper reports a rare case of association between takotsubo and hip fracture surgery , which has been described only by two previous studies , .\nthe female patient we describe , an 81-year - old caucasian woman living at home with a son , was completely independent in katz s basic activities of daily living ( adl = 6/6 ) and lawton s instrumental activities of daily living scales ( iadl = 8/8 ) before the hospitalization . her clinical history evidenced osteoporosis with multiple previous vertebral incomplete collapses , in treatment with oral calcium and vitamin d , hypertension controlled with ramipril , and dyslipidemia for which she took statins .\nshe had no cognitive decline ( normal score at iqcode questionnaire ) , allergies , or weight loss .\nthe woman was admitted during night time in the emergency department ( ed ) of san gerardo university hospital after an accidental fall at home , reporting trauma of the right hip .\n1a ) and partial collapse of multiple vertebrae , the latter without evidence of recent fractures .\nno significant abnormalities were reported at the blood examinations ( i.e. , blood count , electrolytes , liver and kidney function indexes , protein electrophoresis , coagulation parameters , blood gases ) or at the standard electrocardiogram ( ecg , fig .\nthe patient was firstly admitted in the orthopedic ward , and then transferred to the orthogeriatric unit ( ogu , within the geriatric ward ) the day after , once the geriatricians confirmed the eligibility criteria for admission .\nthe comprehensive geriatric assessment did not reveal cognitive deterioration or delirium ( 4at score = 2/12 ) .\nthe pain was on average well controlled with the standard protocol of treatment ( acetaminophen 1 g three times intravenously / day ) .\nscore = 2 ) , which was performed 60 h after the admission .\nten minutes after the injection of cement , when the orthopedic surgeons were performing haemostatic maneuvers and a check of joint movements , the surgical act was complicated by severe bradycardia and cardiogenic shock with consequent cardio - pulmonary arrest . without perturbing the sterility of the surgical site ,\nthe patient was placed supine and promptly treated with cardiopulmonary resuscitation maneuvers , oro - tracheal intubation , and intravenous administration of atropine and epinephrine , obtaining return of spontaneous circulation after 7 min .\nupon restoration of spontaneous circulation , the surgical procedure was completed with saline washing , local instillation of tranexamic acid , layered suture , and plain medication with plaster . the first suspected diagnosis , considering the time relationship with cement injection , was bone cement implantation syndrome ( bcis ) .\nthe patient was then transferred from the operating theater to the intensive care unit ( icu ) , where dopamine ( 5.33 mcg / kg / min , increased to 16 mcg / kg / min ) and norepinephrine ( 0.060.13 mcg / kg / min ) were administered intravenously reaching treatment maximization .\nhydroelectrolytic solutions ( 3500 ml ) were infused to increase the circulating volume and furosemide 40 mg iv was administered to stimulate the diuresis . in the absence of clinical benefits , due to the persistence of hypotension ( systolic blood pressure = 80 mmhg , mean arterial pressure = 50 mmhg ) and the presence of sinus tachycardia , the anesthetist added bisoprolol 1.25 mg four times / day .\nthe echocardiography revealed akinesia of the apex and the mid segment of the septum , extending to the anterior and infero - lateral cardiac wall , accompanied by apical ballooning and significant reduction of the left ventricular ejection fraction ( lvef = 25%30% during amine iv infusion ) .\nadditional examinations excluded the presence of cerebrovascular diseases , myocarditis , hypertrophic cardiomyopathy , and pheocromocytoma .\nthese results oriented toward a diagnosis of takotsubo syndrome , so that the cardiologist prescribed iv treatment with heparin ( 2000 ui in bolus + 20,000 ui in 24 h ) , gradually reduced and discontinued the aminic support , and positioned an intraortic balloon pump .\nthe day after surgery , despite an observed initial reduction of the troponin t levels ( ctnt = 185 ng / ml after 24 h , 154 ng / ml after 32 h ) , the echocardiography showed further reduction of the lvef ( 20% ) with apical akinesia in toto .\nthe finding of anemia ( hb = 8.5 g / dl , mcv = 78.5 fl ) was corrected with the transfusion of 2 units of concentrated red blood cells .\non the second post - operative day , considering the persistence of low cardiac output and atrial tachycardia , the patient started iv treatment with levosimendan 0.1 mcg / kg / min for 7 h , amiodarone 907 mcg / day and metoprolol 2 mg , with gradual amelioration of cardiac output and heart rate . during the third post - operative day we discontinued iv treatment with heparin\n, we removed the intraortic balloon pump and the oro - tracheal device , supporting the patient with low - intensity oxygen by mask .\ntherapy with acetylsalicylic acid 100 mg / day and captopril 6.25 mg three times / day was initiated . on the fourth post - operative day\nwe report a single episode of hyperactive delirium occurred during the night , efficiently managed with the administration of haloperidol 2 mg intramuscular + quetiapine 50 mg per os . during the fifth post - operative day\nshe was transferred to the cardiology icu , where she underwent echocardiography re - evaluation that showed significant restore of the contractile function ( lvef = 56% ) . on the seventh post - operative day\nthe patient was transferred back to the ogu , where she started specific physical therapy oriented towards passive and active mobilization of the right leg , achievement and maintenance of the standing position , and ambulation with the support of a walker . before discharge ,\nthe hemoglobin levels were stabilized ( hb = 12.3 g / dl ) . during the hospital\nshe was discharged sixteen days after the operation and the takotsubo syndrome , in good physical and mental conditions ( mmse score before discharge = 25/30 ) , able to walk ( walker + supervision ) without pain in the surgical area .\nthe follow - up performed two months after surgery revealed absence of cardiac symptoms and good recovery of the walking ability with a walking stick .\nwe suggested to continue strengthening the lower limb muscles with domiciliary physiotherapy and allowed walking without any aid . at the 6-month follow - up , the woman was still asymptomatic from a cardiovascular point of view .\nshe reached a functional level comparable with the pre - fracture status ( katz s adl = 6/6 , lawton s iadl = 7/8 ) .\nshe was able to walk without aids at home , but she needed a walking stick when going outside because of a residual fear of falling .\nfinally , the echocardiogram confirmed good cardiac function ( lvef = 55% ) in the absence of other abnormalities . her son , the caregiver living with her , confirmed an overall good functional and nutritional status and no signs of cognitive decline compared with the pre - fracture status .\nthe patient fulfills several criteria for a diagnosis of takotsubo syndrome : physically stressful event as a trigger , female elderly patient ( at higher risk than young subjects and males ) , apical ballooning with akinesia ( echocardiogram ) , st - segment alterations immediately after the onset ( electrocardiogram ) , lack of significant coronary artery stenosis , recovery of the left ventricular function . indeed\n, approximately 90% of the cases occur in the female population , mostly between 58 and 75 years of age , though it is not uncommon among older individuals , . in this case report\n, the symptomatology seemed to be triggered by the injection of pressurized cement during the hemiarthroplasty procedure , mimicking a bcis of grade 3 ( the more severe grade ) with acute myocardial infarction , accompanied by the classic instrumental cardiac findings .\nbcis was previously reported to be a sporadic adverse event of bone cement injection , still incompletely understood , and was defined only recently .\nit is characterized by the association of multiple signs of different severity , which contribute to a heterogeneous presentation : hypoxia , hypotension , alteration of vascular pulmonary resistance , cardiac arrhythmias , and cardiac arrest . however , in this case , the coronary angiography did not show major obstructions or arterial abnormalities , and the echocardiography did not demonstrate the presence of emboli , thus suggesting a different diagnosis and orienting the physicians toward takotsubo cardiomyopathy .\nthis is the second case of takotsubo we recently encountered in our medical practice , the first being described in 2012 in an 80-year - old woman with severe alzheimer s disease .\npathophysiological mechanisms underlying takotsubo are still not well understood , and the reported cases suggest a number of potential etiologies . in several cases a multifactorial mechanism might be involved , and different variants of the classic takotsubo syndrome have been progressively described , , . altogether , a single pathophysiological mechanism does not clarify the existence of several takotusbo s variants .\nhip fracture and the related surgery are even more stressful experiences : healthcare professionals working in this area should be aware of the severe physical ( pain , immobility , functional disability ) and psychological / emotional ( transfers , total dependence , anxiety ) burden that affects the geriatric population .\nstrength of our approach was the availability and coordination of multiple specialists as consultants 24/24 h , with the geriatrician as the primary attendant according to our orthogeriatric protocol of co - management .\nthese allowed to set up promptly the necessary support therapies and instrumental evaluations in order to identify the potentially life - threatening diagnosis .\nlimitations include the initially wrong diagnostic orientation and the resources required to complete the differential diagnosis before confirming the takotsubo .\ndespite being a rare condition , takotsubo syndrome is a possible differential diagnosis of the bcis , which recently emerged \nregardless its severity as a frequent complication of surgical orthopedic procedures involving the pressurized injection of bone cement , with a prevalence of about 2530% , . moreover , porto et al . recently reviewed the correlation between neurologic disorders and transient left ventricular dysfunction , called neurogenic stunned myocardium and characterized by findings which resemble the classic takotsubo cardiomyopathy .\nthe authors concluded that the available literature suggests treating them as different entities . to the best of our knowledge , the association of takotsubo syndrome with hip fracture in the preoperative phase or after surgery has been rarely reported ( two cases ) .\n, the correct management of elderly subjects could potentially reduce the stress experience related with hip fracture . promoting the gentle care \ninformed consent for the acquisition of data to present in this case report was obtained during the hospitalization , and signed by the patient itself .\nthe consent form is stored in the archive of san gerardo university hospital ( monza , italy ) .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .\nall demographic and patient - specific personal information have been de - identified according to the italian law for the privacy and protection of personal information ( codice in materia di protezione dei dati personali , d. lgs .\ndp , mc , and gb took care of the patient during the hospitalization and obtained informed consent for this report .", "answer": "highlightsdespite the good prognosis when diagnosed early , takotsubo is a life - threatening event.takotsubo must be differentiated from bone cement implantation syndrome ( grade 23).a portable ultrasound scanner allows recognizing the apical ballooning and akinesia hallmark.approaches to reduce the hospitalization - related stress must be pursued in the elderly .", "id": 834} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napart from the correlation studies mentioned above , the ability to innovate and solve novel problems flexibly , proxies for flexible cognitive capacities and potentially for domain - general intelligence , have not been investigated comparatively .\nfew experimental studies have specifically focused on innovativeness , and flexible problem solving per se .\nthe majority of experiments in animal cognition , in both the physical and social domain , present animals with specific problems and investigate how the animals solve them in order to examine specific cognitive abilities / processes .\nmostly , these tasks have been tailored to be ecologically valid for one particular species , or have focused on contexts/ questions so specific that they could not be reproduced in other species easily ( e.g. , dolphins ; food - storing srub jays ) .\nother problem solving tasks , particularly in physical cognition , have secondarily become comparative paradigms and have been established as so - called \nbenchmark tests for examining the existence of certain cognitive abilities in different species , e.g. , the trap - tube for examining an understanding of causality in terms of surface continuity , povinelli s cane task and heinrich s string - pulling task for testing responsiveness to connectivity etc .\nmost of these typically started off from a single experiment designed for testing a particular species and some subsequently applied to other species , sometimes without paying sufficient attention to species differences in morphological ( hand or beak ) , behavioral ( e.g. , object exploration , affordance learning ) and perceptual features ( e.g. , field of vision ) , in addition to psychological variables ( such as motivational , emotional or attentional states , inhibitory control or neophobia / neophilia ) . yet\nall these factors can potentially have a big impact masking cognitive skills actually present in a species and producing misrepresentative results .\nanother methodological problem of comparative cognition is that paradigms are applied to many species , but with slightly converted methodologies ( better fitting the newly compared species demands ) , hence at a cost of comparability . if the methodology is not standardised , it is hard to interpret the findings of comparative studies , because any detected differences between species could be owing to the different procedures .\nan odd handicap for comparative cognition in this context appears to be that modification or \nimprovement of an already used comparative paradigm , instead of merely replicating it in a new species , may increase the chances of a study to become published .\noften however , a direct comparison would have been scientifically more valuable than yet another improvement to an existing experimental paradigm . recently ,\nthis has been acknowledged and several research groups have begun to run comparative studies with the exact same methods .\nthe difficulty of comparative cognition therefore is to find comparative paradigms that are compatible with many different species ( i.e. , that are ecologically valid for all the species to be compared , and not influenced by potentially confounding species - specific variables ) , and that have a standardised methodology that can be applied to different species in exactly the same way .\nbecause of the potentially confounding impact of different methodologies , the same cognitive ability should be investigated with not just a single but several tests with slightly different angles in any given species .\nrecently , comparative studies carry out entire batteries in different species tests , e.g. , those comparing cognitive abilities in the social and physical domain . yet\n, what is missing is to have a battery of tests establishing species differences that might affect performance in different cognitive tests , such as object exploration , motivation , attentiveness and fear / neophobia .\na new such comparative approach is the multi - access - box ( mab ) , recently published in plos one ( see fig . 1 ) .\nit presents the animal with a novel problem that can be solved in four different ways , thus offering the possibility to examine species differences in how novel problems are perceived , explored and approached and in which order solution(s ) are discovered .\nthis provides several data that can be used for establishing a behavioral ( e.g. , object exploration , ) and psychological profile ( e.g. , motivation , flexibility , impulsivity , persistence , inhibitory control ) and hence extract behavioral and perceptual determinants of different species performance in the tasks .\nsimultaneously , it is a suitable paradigm to collect data about problem solving ability , innovativeness and flexibility , i.e. , theoretical covariates of general intelligence , across species in a standardized manner .\nmulti access box ( mab ) ( as in plos one , copyright 2011 by the public library of science . reprinted with permission of the author ) .\na food reward presented in the center of a transparent box can be retrieved by one of four possible methods , which are built in the four walls of the mab : opening a window , pulling a string , inserting a ball or inserting as stick tool .\nthe mab approach comprises not just one but several solutions to an extractive foraging problem at the same time ( food out of reach in the center of a transparent box ) , i.e. it consists of a battery of alternative tasks that all lead to the same goal .\ntwo solutions ( opening a window and pulling a string ) could be discovered by haptic exploration ( touching the box at particular sites ) , while the other two additionally required the handling of objects , either wooden sticks or marbles , as tools ( inserting a ball or a stick tool into specific openings ) .\nthe other important feature of the mab is that subjects were forced to continue exploring alternative solutions , once they had successfully discovered and consistently used one particular solution , by blocking the one in use .\nthis creates an order system which allows to detect species differences in which tasks are approached and explored first and how , how many solutions are discovered and how fast , whether and how quickly the subjects switch between options or whether they focus or settle on particular ones , as well as which tasks are problematic and why . in this manner\nwe can detect not only species differences in problem solving performance , but also learn about the various underlying non - cognitive factors that may affect it .\nalthough designed for large scale comparisons of different closely- and distantly related species from different ecological backgrounds , the initial mab study compared just two avian species from different families , a corvid , the new caledonian crow ( ncc ; corvus moneduloides ) and a parrot , the kea ( nestor notabilis ) ( see fig . 2 ) .\nboth species are known for their large brains , their innovativeness and problem solving skills , but nccs are naturally tool - using species while kea have not been observed to use tools in the wild , but are famous for their neophilia .\nsubjects were exposed to the transparent mab with the food reward in the center , which could be extracted by the four different methods corresponding to the four walls of the box .\nonce a method was mastered , it was blocked and the bird s performance in reaching criterion in any of the others was recorded until all four methods had been discovered . figure 2 .\nkea and new caledonian crow using the stick ( left ) and the ball - shaped ( right ) tool on the multi access box .\nfound that one kea and one ncc detected all four solutions , demonstrating that the solutions offered were within both species capacity .\nthe kea were much quicker in discovering multiple solutions than the habitually tool - using nccs and showed more individual variation .\nthe keas were also more flexible once openings were blocked , switching to other solutions much quicker than the ncc .\ninnovation rate as well as performance in this paradigm were strongly impacted by differences in exploration technique and neophilia rather than by cognitive discrepancies .\nthe highly neophilic kea explored the apparatus more in a haptic than in a visual manner .\nthey found its functional properties , while manipulating the affordances of the mab they perceived as most salient .\nin contrast to the kea and probably due to their more visually guided exploration technique , the nc crows had problems solving the window solution .\nthe window mechanism could not be deduced by visual inspection alone ( without knowledge of hinge - mechanisms ) , but could be readily discovered by haptic exploration .\nanother difference was that the nc crows tended to persist with the first option that worked , whereas the kea , owing to their higher level of neophila , switched between solutions .\ndifferences in beak morphology also affected the birds performance : the kea had problems maneuvering the stick tool because of their beak curvature , whereas the crows with their straight beaks had a good grip of the tools . yet\n, the nc crows used their straight beak more for pecking than tearing actions , which would have been advantageous in detecting the mab apparatus s affordances in case of the window option ( grasping and pulling the window crank ) .\nan important new tool that could be incorporated in the mab procedure and that could be revealing in comparisons of flexible problem solving may be \nreversal learning. species with different ecological backgrounds may have been selected for different strategies in trial and error learning and problem solving . in terms of energy pay - off it may\n, under certain circumstances , be advantageous to persist ( e.g. , in the case of nccs fishing for particularly nutritious wood - boring beetle larvae in rotten wood as , which can take considerable time but has a high potential return ) .\nin other contexts it may save energy to give up if something does not work and try something else instead .\nreversal learning tasks reflect differences in flexibility and are informative of how fast animals can adjust their behavior to new external feedback , let go of previously reinforced behavioral patterns , but at the same time they offer a measure of persistence .\nto illustrate how reversal learning could be implemented , we present some data not published in the original auersperg et al .\nonce a subject had discovered all solutions , we incorporated a reversal learning task for the two solutions incorporating a tool ( see fig . 2 ) .\nfor the two successful subjects , uk , a ncc and kermit , a kea , the last used tool option was blocked and the previous tool option was reopened .\nas can be seen the crow required a similar amount of trials to relearn the previous option as the kea , although of course data on more individuals would be desirable .\nillustrate how even diminutive differences in non - cognitive behavioral components such as neophilia or morphology can mask and/or interfere with the respective cognition involved and impact on the species performance .\nit highlights how different performance in problem solving task are not always symptomatic of species differences in cognitive ability or general intelligence .\nit highlights in particular , what major impact differences in object exploration ( haptic or visual exploration mode ) and affordance learning , which have only recently become a topic in animal cognition , can have on performance in artificial experimental tasks , and hence how this affects the comparability of two species in the same task . in future comparative research , establishing behavioral and psychological profiles of the species to be compared ought to precede comparative tests of specific cognitive skills or general intelligence .\nthis may help to identify problem solving tasks that are equivalently applicable to the target species and hence achieve a high degree of", "answer": "comparative cognition aims at unfolding the cognitive processes underlying animal behavior and their evolution , and is concerned with testing hypotheses about the evolution of the brain and intelligence in general . \n it is a developing field still challenged by conceptual and methodological issues . \n systematic cross - species comparisons of cognitive abilities , taking both phylogeny and ecology into account are still scarce . \n one major reason for this is that it is very hard to find universally applicable paradigms that can be used to investigate the same cognitive ability or \n general intelligence in several species . \n many comparative paradigms have not paid sufficient attention to interspecific differences in anatomical , behavioral and perceptual features , besides psychological variables such as motivation , attentiveness or neophobia , thus potentially producing misrepresentative results . a new stance for future comparative research may be to establish behavioral and psychological profiles prior or alongside to comparing specific cognitive skills across species . \n potentially revealing profiles could be obtained from examining species differences in how novel experimental ( extractive foraging ) tasks are explored and approached , how solutions are discovered and which ones are preferred , how flexibly multiple solutions are used and how much individual variation occurs , before proceeding to more detailed tests . \n such new comparative approach is the multi - access - box . \n it presents the animal with a novel problem that can be solved in several ways thus offering the possibility to examine species differences in all the above , and extract behavioral and perceptual determinants of their performance . \n simultaneously , it is a suitable paradigm to collect comparative data about flexibility , innovativeness and problem solving ability , i.e. , theoretical covariates of \n general intelligence , in a standardized manner .", "id": 835} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsarcoidosis is a multisystemic , granulomatous disease of unknown etiology that may affect any organ system .\nit is characterized by the accumulation of t lymphocytes and mononuclear phagocytes with the formation of noncaseating epithelioid granulomas in affected organs .\nthe trigger for this t cell and macrophage interaction is still uncertain , although bacterial , viral , and environmental antigens have all been studied .\nrecent literatures renewed the interest in mycobacteria as a causative agent in sarcoidosis tissue [ 2 , 3 ] . here\nwe present a case of presumed ocular sarcoidosis diagnosed by ocular manifestation and treatment course , who developed tuberculous lymphadenopathy 6 years later without recurrence of ocular inflammation .\na 35-year - old female was referred to our department with severe visual impairment for months .\nshe was quite healthy until 1 year ago when she began to suffer recurrent episodes of uveitis with mutton fat keratic precipitates ( kps ) in both eyes . on presentation ,\nocular examination showed mild anterior uveitis with mutton fat kps and dense vitreous hemorrhage in both eyes .\nsystemic workup including general physical examination , complete blood counting , differential classification , blood biochemical tests , rheumatic factor , antinuclear antibody , human immunodeficiency virus , venereal disease research laboratory test , anticardiolipin antibody , and chest radiography were within normal ranges . due to persistent vitreous hemorrhage and disabled vision ,\npars plana vitrectomy was performed in the left eye and then the right eye 2 months later .\nsign of peripheral vasculitis with nodular choroid infiltration was noted during operation in both eyes .\ngallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinum ( fig . 1 ) .\nchest computed tomography ( ct ) showed a small ground glass opacity nodule in the subpleural space of the right lower lobe , more in favor of inflammatory process .\nbased on these findings , ocular sarcoidosis was impressed and systemic and topical steroids administered in a tapering dose over 6 months .\nunfortunately , painless enlargement of lymph node at her right neck was noted 6 years later .\nlymph node biopsy showed granuloma with caseous necrosis , langhans giant cell , as well as acid - fast bacilli ( fig . 2 ) .\nthree combined antituberculosis medications ( rifampin , isoniazid , and pyrazinamide ) were given for 6 months .\nthe eyes remained silent except cataract progression and glaucoma under two medications during this period ( fig . \n1gallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinumfig . \n2pathological finding from lymph node biopsy showed granuloma with caseous necrosis ( hematoxylin and eosin , 40 ) ( a ) , langhans giant cell ( hematoxylin and eosin , 400 ) ( b ) , as well as acid - fast bacilli ( kinyoun 's crystal fuchsin acid - fast stain , 1,000 ) ( c)fig . \n3postoperative color fundus picture of both eyes showed sheathing vessels and scattered laser scars at the inferior retina . a right eye .\nb left eye gallium-67 scans showed panda sign of increased uptake in lacrimal glands and lambda sign of lymph nodes in the mediastinum pathological finding from lymph node biopsy showed granuloma with caseous necrosis ( hematoxylin and eosin , 40 ) ( a ) , langhans giant cell ( hematoxylin and eosin , 400 ) ( b ) , as well as acid - fast bacilli ( kinyoun 's crystal fuchsin acid - fast stain , 1,000 ) ( c ) postoperative color fundus picture of both eyes showed sheathing vessels and scattered laser scars at the inferior retina . a right eye .\nthe gold standard for diagnosis of sarcoidosis is histopathologic examination . considering the fact that ocular sarcoidosis may occur in the absence of apparent systemic involvement , and the fact that biopsy is usually reluctantly accepted by uveitis patients , the international workshop on ocular sarcoidosis ( iwos ) established an international criteria for the diagnosis of ocular sarcoidosis .\nalthough there was no pathologic proof of sarcoidosis in our case , her ocular manifestations met at least five of the iwos criteria . though the lacrimal gland uptake of gallium ( panda sign ) is not a specific sign for sarcoidosis , her simultaneous presence of lambda and panda sign on ga-67 scans gave some support to sarcoidosis .\nas guided , other granulomatous diseases , including tuberculosis , foreign body reaction , bacterial and viral infections , should be excluded before the diagnosis of sarcoidosis .\nother laboratory and image study ruled out the other possible etiologies . besides , the ocular inflammation subsided after pars plana vitrectomy and systemic corticosteroid .\nthere was no recurrence of inflammation even at the time of tuberculous lymphadenopathy . presumed ocular sarcoidosis was impressed based on the ocular manifestations and treatment course .\nwe could not make any conclusion whether ocular sarcoidosis and tb lymphadenopathy in this patient is just coincident or in real association with each other . despite the increasing understanding of the immune responses behind the formation and maintenance of the granulomatous process in sarcoidosis\nmycobacteria have been implicated as a cause of sarcoidosis , although the demonstration of mycobacterial dna was inconsistent in different reports [ 6 , 7 ] .\nrecent studies by detecting mycobacterium tuberculosis catalase peroxidase have renewed interest in mycobacteria as a causative agent in sarcoidosis [ 2 , 3 ] . in our case , tb was ruled initially due to negative results of chest x - ray , aqueous tb culture , and pcr .\ntuberculin skin test was not done as our cdc did not identify the significance of ppd in adult who received routine bacille calmette guerin vaccination .\nthe ocular inflammation revolved after systemic steroid , and remained silent even at the presence of tb lymphadenopathy .\nour speculation is that the presumed ocular sarcoidosis might be triggered by tb antigen in extraocular infection , which reactivated and presented as tb lymphadenopathy 6 years later .\ntb could occur coincidently or in association with sarcoidosis , continued follow - up is important for patients with ocular sarcoidosis , even in silent case .", "answer": "tuberculosis and sarcoidosis share similarity in histopathologic findings and clinically occur in association with each other occasionally . \n tuberculosis should always be ruled out before the diagnosis of sarcoidosis . \n but , the diagnosis is often complicated , especially in extrapulmonary cases . here \n we present a case of bilateral vitreous hemorrhage with uveitis . \n ocular sarcoidosis was initially diagnosed based on the characteristic ocular findings , negative results on chest radiography , tuberculosis culture , and polymerase chain reaction of aqueous , as well as simultaneous presence of panda and lambda sign on gallium-67 scans . \n the ocular condition improved after pars plana vitrectomy and systemic steroid therapy . \n however , tb lymphadenopathy but no recurrent ocular inflammation was found 6 years later . \n the patient received anti - tb treatment for 6 months thereafter . \n the eyes remained silent except cataract progression and glaucoma under two medications during this period . in conclusion , tb could occur coincidently or in association with sarcoidosis , continued follow - up is important for patients with ocular sarcoidosis .", "id": 836} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nimmunocompromised patients might bear a variety of presentations such as rhino - orbito - cerebral , pulmonary , gastrointestinal , cutaneous , central nervous system and disseminated form .\nrhino - orbito - cerebral and pulmonary mucormycosis are the most common forms ; the latter progresses rapidly to devastating diseases .\npresentation of pulmonary mucormycosis may be confused with several infectious and non infectious diseases ; therefore its diagnosis is difficult .\nchest ct scan of a patient with pulmonary mucormycosis might demonstrate such presentations as air crescent sign , ct halo sign , solitary or multiple pulmonary nodules or masses , bronchopulmonary fistula and pulmonary artery pseudo aneurysm .\nthe occurrence of pneumothorax and its subsequent rhs along with sinusitis , supported by radiology and pathology in a 33 years old patient , is considered as a rare case of pulmonary mucormycosis .\nfollowing is the treatment history of a man , 33 years old in july 2014 ( day + 14 ) , when he died in our hospital as a result of multiorgan failure .\nhe was a farmer , married , with no history of alcohol consumption , illicit drugs use and extramarital relationships . on day 330 : because of edema he visited a medical center in another city , where he was admitted and membranous glomerulonephritis was diagnosed .\nconsequently the followings administered ; prednisolone and cyclosporine for 2 months , cellcept for 1 month , prednisolone and cyclophosphomide for 7 months . on day 75 : because of progressive generalized edema he was admitted again .\nhe was discharged under treatment with prednisolone ( 50 mg / daily ) and tacrolymus ( 1 cap / bd ) . during the next 2 months he was feeling fine . on day 28 , he travelled to village for a few days and he had close contact with sheep . on day\n14 the patient reported fever , cough and dyspnea with mild erythema and pain in right eye .\nanorexia , weakness , dyspnea and conjunctivitis developed and persisted despite of outpatient antibiotic treatment . in the emergency department (\nday 0 ) : the patient suffered from dyspnea , weakness and right eye pain . on examination , he was agitated but completely conscious with diaphoretic skin .\nthe vital signs have been as follows ; temperature , 36.7 c ; blood pressure , 100/60 mmgh ; pulse rate , 99 beats per minute ; respiratory rate , 22 beats per minute and oxygen saturation in air room , 99% .\nin right eye , there was moderate conjunctivitis with eyelid erythema ; its movement was normal .\nthe first day chest ct scan revealed large pleural effusion with pneumothorax in the left side and a shift of mediastinum to the right side .\n1 ) . consequently drainage with chest tube was administered by the surgeon immediately . because of the immunocompromised state of the patient , parenteral trimethoprim- sulfamethaxazol ( 160 mg / iv / tds ) and meropenem ( 1 g / iv / bd ) were administered for pneumocystis jiroveci and multi drug resistant organisms .\nwe also started fluconazole for oral lesions . on day + 3 , right eye erythema was extended with small size necrosis in right nasal ala without bleeding ( fig .\nwith doubt of rhino - orbital mucormycosis , biopsies of tongue and nasal septa were carried out and amphotericin b deoxycholate ( 1 mg / kg / daily ) was administered . on day + 4\n, paranasal sinuses ( pns ) ct scan revealed soft tissue density lesion in left ethmoid sinus and nasal passage with extension to left orbit ( fig .\n, he was transferred to intensive care unit ( icu ) because of respiratory distress and was intubated after 48 h ; his conscious level was 14+t/15 .\nsmear of sputum for acid fast bacilli , stain and culture of sputum for pneumocystis jiroveci were negative .\nhiv antibody test , d - dimer enzyme -linked immunosorbent assay ( elisa ) and collagen vascular diseases screening tests were negative ( table 1 ) .\npleural fluid cytologic examination and polymerase chain reaction ( pcr ) for fungi were negative . on day + 6 , laboratory results revealed pancytopenia ( table 1 ) , however in peripheral blood smear there was no schistocyte or immature cells .\nbone marrow biopsy which could help in finding the cause of pancytopenia was nevertheless postponed due to the patient 's poor condition and low platelet count .\nmeanwhile his blood pressure was decreased and we started inotropic drugs.hemodynamic instability of the patient prohibited further attempts such as bronchoscopy and ct guided lung biopsy to identify the causative agent . on day + 9 ,\nsection of tounge biopsy showed ulcerated squamous epithelial mucosa with subepithelial fibro fatty tissue and skeletal muscle fibers of tongue that is on site of ulceration .\nthe inflammatory granulation tissue and inflammatory multinucleated giant cells were also seen in gimsa staining , but no cyst and trophozoite of pneumocystis jiroveci were identified .\npulmonary mucormycosis is a devastating infection when it affects immunocompromised patients such as diabetes mellitus , hematologic malignancies , chronic renal failure , post transplantaion and immunosuppressed persons . herein , we present a rhino - orbital mucormycosis with pulmonary involvement .\nreticulation inside the rhs , presence of pleural effusion , multiple nodules and concomitant rhino - orbital mucormycosis as well as documented pathology , collectively were considered as indicating that pulmonary involvement has been due to mucormycosis .\nthe pathological finding is achieved by tongue tissue ; lung biopsy has not been possible due to poor condition of the patient .\nour case was an immunocompromised patient with documented rhino - orbital mucormycosis ( figs . 3 , 5 and 6 ) .\nchest ct scan showed bilateral pleural effusion , multiple nodules and rhs with thin reticulation ( figs . 1 and 4 ) .\nalthough histopathology findings are usually needed to establish the diagnosis of pulmonary mucormycosis , using ct imaging and clinical presentation we can avoid the invasive procedures such as lung biopsy\n. there are few case reports of pneumothorax in pulmonary mucormycosis , some of which are iatrogenic during mechanical ventilation and bronchoscopic procedure [ 911 ] .\ncombined mucormycosis and methicillin - resistant staphylococcus aureus ( mrsa ) were found to be responsible for life threatening pneumothorax in an immunocompromised patient .\nmucormycosis and aspergillus have been recognized as leading to pneumonia and pneunothorax in a dialysis patient .\nhowever , spontaneous pneumothorax in pulmonary mucormycosis that is followed by rhs seems to be a unique case . based on patient 's background and clinical signs , amphotericin b deoxycholate ( 1 mg\nthe lower dose of antifungal drug has been due to the patient 's renal insufficiency .\nambisome would have certainly been a better choice than amphotericin b ; however , the former has not been available in iran .\nhowever the lack of bone erosion in sinus ct scan , delay in pathologic result and patient 's poor clinical condition , lead into the reluctance of surgeon for extensive debridement that had negative impact on patient 's prognosis .\npneumothorax which is due to mucormycosis can be fatal particularly in immunocompromised persons , so clinicians should take immediate measures ( follow up imaging and pathology ) to confirm or reject the presence of invasive fungal infection . if confirmed , antifungal therapy is necessary as soon as possible .", "answer": "mucormycosis , an invasive fungus with a variety of clinical presentation , is a devastating infection in immunocompromised host . here \n an unusual case of pulmonary mucormycosis is introduced in an immunodeficient patient in which pneumothorax was followed by reversed halo sign ( rhs ) . \n the clinicians , who visit immunocompromised persons with pneumothorax , should be considerate to take immediate imaging and pathologic measures to confirm or reject mucormycosis .", "id": 837} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfirst performed in 1989 , laparoscopic cholecystectomy quickly became the gold standard for surgical extirpation of the gallbladder . soon after , reports began to emerge of an increased incidence of significant bile duct injuries . reported injury rates varied from 0.1% to 2.2% compared with 0.1% for open cholecystectomy .\nthe increased rate of bile duct injury has been attributed to a steep learning curve for laparoscopic cholecystectomy .\nsubsequent referral to tertiary centers for repair of transected common bile ducts resulted in published series that outlined the mechanisms of injury .\nrisk factors for iatrogenic injury to the common duct appear to be the surgeon 's inexperience , patient obesity , scarring and acute inflammation .\na common factor in the reported cases of bile duct injury is the misidentification of common duct for cystic duct , resulting in resection of a portion of the common bile and hepatic ducts and a right hepatic artery injury .\nprecautions suggested to decrease the possibility of bile duct injury have included : routine cystic duct cholangiography , cholecystocholangiography , confirmed identification of the junction of the cystic duct with the common bile and hepatic ducts and identification of the junction of the cystic artery with the right hepatic artery .\nour experience with laparoscopic cholecystectomy supports the importance of anatomic identification in the safe performance of the procedure and also suggests the presence of a useful and reproducible anatomic landmark which can help define a zone of safe dissection within the triangle of calot .\nthis study is derived from a single surgeon 's experience with more than 300 laparoscopic cholecystectomies performed since 1991 .\nall patients with acute or chronic gallbladder disease were considered for the laparoscopic approach with the exception of those with suspected gallbladder masses or neoplasm .\nthe anatomy of the biliary tree was defined prior to division of the cystic duct and artery .\ncholangiograms were abandoned only if the lumen of the cystic duct would not accommodate the epidural catheter used for this purpose . during 1996 ,\npatients were chosen in one of three representative categories as they randomly presented in the course of our practice .\nthese were chronic disease , acutely inflamed gallbladder and intra - operatively identified aberrant anatomy .\ni.m . , a 67 year - old - female with biliary colic systems and ultrasound proven cholecystolithiasis , underwent outpatient laparoscopic cholecystectomy .\ntwo 1 mm veins were demonstrated within the triangle of calot between the cystic duct and cystic artery ( figure 1 ) .\ncase i : acute chdeaystititis and multiple cystic veins m.b . , a 56-year - old female with biliary colic symptoms and cholecystolithiasis on ultrasound , underwent outpatient laparoscopic cholecystectomy .\na small venous structure was found to be crossing it and extending to the gallbladder ( figure 2 ) .\nfurther dissection showed the artery to be an aberrant right hepatic artery with a short cystic artery identified later .\n, a 49-year - old female , was admitted with acute abdominal pain , fever , leukocytosis and thickened gallbladder containing stones on ultrasound .\ndissection within the triangle of calot demonstrated venous structures between the later confirmed cystic duct and artery ( figure 3 ) .\nearly in our experience with laparoscopic cholecystectomy , the presence of small tubular structures within the triangle of calot became evident as being necessarily divided to proceed with the dissection . among these was a structure that presented as a bridge between the cystic artery and duct ; the division of which , unless controlled , resulted in insignificant but annoying bleeding .\nit quickly became a standard part of the procedure to clip or cauterize this ves sel during the dissection .\nits color and non - pulsatile bleeding when divided , indicated that this was a vein , ostensibly unnamed .\nit was subsequently determined that these venous channels were named as the cystic veins and their courses documented in early textbooks of anatomy .\ni.m . , a 67 year - old - female with biliary colic systems and ultrasound proven cholecystolithiasis , underwent outpatient laparoscopic cholecystectomy .\ntwo 1 mm veins were demonstrated within the triangle of calot between the cystic duct and cystic artery ( figure 1 ) .\nm.b . , a 56-year - old female with biliary colic symptoms and cholecystolithiasis on ultrasound , underwent outpatient laparoscopic cholecystectomy .\na small venous structure was found to be crossing it and extending to the gallbladder ( figure 2 ) .\nfurther dissection showed the artery to be an aberrant right hepatic artery with a short cystic artery identified later .\nn.m . , a 49-year - old female , was admitted with acute abdominal pain , fever , leukocytosis and thickened gallbladder containing stones on ultrasound .\ndissection within the triangle of calot demonstrated venous structures between the later confirmed cystic duct and artery ( figure 3 ) .\nearly in our experience with laparoscopic cholecystectomy , the presence of small tubular structures within the triangle of calot became evident as being necessarily divided to proceed with the dissection . among these was a structure that presented as a bridge between the cystic artery and duct ; the division of which , unless controlled , resulted in insignificant but annoying bleeding .\nit quickly became a standard part of the procedure to clip or cauterize this ves sel during the dissection .\nits color and non - pulsatile bleeding when divided , indicated that this was a vein , ostensibly unnamed .\nit was subsequently determined that these venous channels were named as the cystic veins and their courses documented in early textbooks of anatomy .\na consistent anatomic feature during laparoscopic cholecystectomy has been the presence of venous twigs that run parallel to the cystic duct and perpendicular to the common bile duct , bridging the gap between cystic artery and cystic duct . as the veins do not cross the common hepatic duct , their presence can serve as an anatomic feature of a safe dissection space between the important structures of the triangle of calot .\nduring surgical residency a common question intended to \" trip up \" junior residents during division of the cystic artery , has been to ask them to define the cystic vein .\nit is usually pointed out to the less assured that there is no cystic vein per se , but that the venous drainage is through the bed of the liver . in contradistinction to this , however , grant 's anatomy , in illustrating the veins of the extrahepatic bile passages and gallbladder ( figure 4 ) , clearly demonstrates venous drainage directly into the liver , and describes venous twigs which clinging to the passages .... join branches of the portal vein .\ngray 's anatomy of the human body likewise describes cystic veins which join at the neck of the gallbladder to form either single or double cystic veins which flow along the cystic duct and upward along the hepatic ducts .\ntextbooks of surgery , however , do not assign much importance to the venous drainage of the gallbladder .\nthe textbook of surgery edited by sabiston reports only that the venous drainage of the gallbladder and extrahepatic ducts is into the portal vein .\n schwartz 's principles of surgery describes the venous drainage as variable and generally does not run parallel with the arteries . \na prominent surgical atlas similarly omits all veins from it 's anatomic diagrams and does not describe operative management of these structures during the procedure .\none of the differences between laparoscopic and open surgery is that magnification of the anatomy gives a new perspective to the dissection process .\nthe magnified field of view demands meticulous attention to operative detail lest bleeding from a source not significant during open cholecystectomy , completely obscures the field during laparoscopic cholecystectomy .\nthis fractal * anatomic view uncovered the presence of venous structures within the triangle of calot , which , if not clipped or cauterized prior to division , would obscure the operative field . only with experience\ndid we find the presence of the cystic veins to be constant . during difficult cases\n, the cystic veins can serve as a landmark for that space between cystic duct , cystic artery and common bile duct , that allows for safe handling and isolation of these vital structures .\na review of anatomy texts has shown that the cystic veins were known to classical anatomists .\nit was only later that , without apparent clinical relevance , a description of the cystic veins was omitted from surgical textbooks and their very existence devolved into a trick question for unsuspecting house staff .\ni do not doubt that experienced laparoscopic surgeons have encountered these venous structures and are dealing with them on a regular basis , but that they exist as a reliable anatomic feature of the region is not well appreciated .\nits importance , however , may lie in the fact that the cystic vein can serve as a landmark during a difficult laparoscopic cholecystectomy to decrease the risk of inadvertent bile duct injury .", "answer": "the cystic vein , a portion of biliary anatomy whose insignificance in open gallbladder surgery led to its being relegated to mythology , has been rediscovered by the magnified view of laparoscopic surgery . \n its presence is an important anatomic feature that helps distinguish between cystic duct and common hepatic duct , thus diminishing the risk of inadvertent bile duct injury during laparoscopic cholecystectomy .", "id": 838} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npasteurella multocida was first described by revolee in 1877 and further characterized by pasteur in 1880 .\npasteurella species usually have low virulence in humans , but serious manifestations sometimes occur and can lead to bacteremia .\nwe present a patient who developed septic shock as a result of p. multocida bacteremia , presumptively from an intra - abdominal infection .\na 52-year - old african american female was brought to the emergency department for generalized abdominal discomfort , altered mental status , diarrhea , fevers and chills for 4 - 5 days .\nher past medical history was significant for alcohol abuse and alcohol - related liver cirrhosis . in the emergency department , vital signs were as follows : blood pressure of 74/42 mmhg , heart rate of 112 beats / min , respiratory rate of 20 breaths / min and temperature of 98.6 f. remarkable findings on physical examination included jaundice as well as abdominal distention and tenderness to palpation , especially in the right upper quadrant .\nas per family , she did not have recent travels or exposure to sick people .\nthey denied having domestic animals at home or any contact to the patient with pets .\nadmission diagnosis was systemic inflammatory response syndrome with sepsis and septic shock with multi - organic dysfunction syndrome , presumptively secondary to community - acquired pneumonia , possible biliary tract infection ( ascending cholangitis ) , probable spontaneous bacterial peritonitis ( sbp ) and alcoholic hepatitis .\nempiric intravenous antimicrobial therapy , composed by piperacillin / tazobactam ( 2.25 g every 8 h ) and azithromycin ( 500 mg every 24 h ) , was initiated .\nlaboratory results on admission were : a complete blood cell count of 21,000/mm(90% neutrophils ) , a platelet count of 51,000/mm , a sodium level of 127 meq / l , a potassium level of 5.3 meq / l , a bicarbonate level of 15 meq / l and a creatinine level of 6.3 mg / dl .\nalkaline phosphatase level was 290 iu / l , gamma - glutamyl transpeptidase level was 290 u / l and lactate dehydrogenase level was 482\ntotal bilirubin level was 14.5 mg / dl , with a direct bilirubin level of 10.1 mg / dl .\narterial blood gases showed a ph of 7.15 , a pco2 of 23 , and a po2 of 132 while the patient was receiving mechanical ventilation with fio2 of 60% .\nafter 24 h of admission , patient remained in critical condition and requiring maximum doses of vasopressors , despite of what it seems to be the appropriate empiric antimicrobial therapy .\nblood culture system bact - alert 3d was used for the recovery of the organism .\nno minimal inhibitory concentrations for these antimicrobials were reported . in spite of all medical efforts ,\np. multocida is a small gram - negative non - spore forming facultative anaerobe organism that is a natural inhabitant of the normal gastrointestinal flora and the upper respiratory tract of wild and domestic animals , especially cats and dogs .\nit is easily overgrowing by other flora in the sputum and might be regularly missed , as it resembles haemophilus influenzae , francisella tularensis and yersinia pestis .\nthe five species that cause the majority of pasteurellosis are : multocida , septica , canis , stomatis , and dagmatis .\nhuman p. multocida infections have been reported to occur with and without animal exposure , the former mostly associated with the domestic cat and dog bites or scratches .\nmost of the infections involve the skin and soft - tissues and they can be complicated by abscess formation , osteomyelitis or septic arthritis .\nthe respiratory tract is the second most common site of infection with a wide spectrum of diseases that includes rhinosinusitis , tracheobronchitis , epiglottitis , pneumonia , empyema and lung abscesses .\nthe majority of p. multocida pneumonia cases occur in elderly patients with underlying chronic pulmonary disease .\ninvasive forms of p. multocida infection usually occur in immunocompromised patients , such as those with advanced age , chronic renal failure , solid tumors , hematological malignancies , diabetes mellitus or liver cirrhosis .\np. multocida causes a wide variety of disease , including abdominal and pelvic infections , endocarditis , meningitis and endophtalmitis .\nvon graevenitz et al . reviewed 21 proven cases of p. multocida bacteremia . a remarkable number of those cases involved patients with liver diseases , including liver cirrhosis of any etiology , hepatitis and infiltrating tumors .\nimpaired function of the reticuloendothelial system and the presence of portosystemic shunts in patients with liver disease seem to play a major role in the development of bacteremia .\nthis case seems peculiar in that no direct contact with a domestic animal could be documented .\nour patient had a history of alcohol - induced liver cirrhosis , which predisposed her to the development of bacteremia . however , retrospectively , it is difficult to establish the primary source of infection in this case .\nthe findings of the abdominal examination may suggest that the primary source was the intra - abdominal cavity .\nunfortunately , the medical team was not able to performed paracentesis to obtain ascitic fluid for cytology and cultures due to patient s medical condition .\nno abdominal imaging was available . on the other hand , the chest radiography findings of infiltrate and pleural effusion may point the respiratory tract as the primary source of infection .\nwe believed that , given the history of symptoms on admission and the presence of underlying liver disease , the intra - abdominal cavity was the most likely primary source of infection in this patient .\nnasopharyngeal colonization with p. multocida with transient bacteremia and seeding of the peritoneal cavity in immunosupressed cat owners could play an important role in the development of sbp .\nten of these patients were exposed to animals , nine had positive blood cultures and four patients died .\nhowever , penicillin - resistant strains in human infections have been described . in these cases , 2 and 3 generation cephalosporins , macrolides , fluoroquinolones , tetracyclines , and trimethoprim - sulfamethoxazole\noutcome is associated with severity of the infection , the extent of the underlying disease and the early initiation of appropriate therapy .\nalthough cases of bacteremic p. multocida infections has been infrequently reported in the literature , clinicians should considered this organism as an important and potentially lethal pathogen in humans , where it can cause life - threatening infections .\np. multocida should be included in the microbiologic differential diagnosis in patients with underlying chronic liver diseases who presents with possible intra - abdominal infection , even without history of exposure to domestic animals .", "answer": "pasteurella multocida is a gram - negative organism characterized morphologically as coccobacillus . \n it is the commonest organism infecting pet bites . \n however , severe infections may occur in the absence of animal bites or scratches . \n pasteurella multocida serves as an opportunistic pathogen in humans , especially in patients with depressed immune system . \n few cases in the literature identify pasteurella multocida as the causative agent of septic shock , especially in cirrhotic patients . \n we report a patient who presented with septic shock as a result of pasteurella multocida bacteremia , without prior history of animal exposure .", "id": 839} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ninnate immunity mediated through pamp recognition by prrs is the earliest stage of immunity against viral infection .\nthe subsequent modulation of the adaptive immune response by prr signaling has been studied using cells and mice deficient in specific tlrs , rlrs , or their associated signaling adaptor proteins .\nrecent studies demonstrated , for example , that the absence of specific tlr pathways impairs adaptive immune responses against a variety of viruses ( 18 , 19 ) .\nrlr signaling also seems to be critical for the outcome of japanese encephalitis virus ( jev ) , vesicular stomatitis virus ( vsv ) , influenza virus , and encephalomyocarditis virus ( emcv ) infection ( 11 , 20 , 21 ) . in mice lacking rig - i ,\nstimulator 1 , jev , vsv , influenza virus , and ecmv were more virulent and replicated to higher levels than in wild - type mice , suggesting that rlr pathways are essential for controlling infection by these viruses ( 11 , 21 , 22 ) .\nfor example , irf3 target genes induced by rlr signaling directly control viral replication in infected tissues ( 23 , 24 ) .\nthus , depending on the nature of virus infection , tlrs and rlrs may work together or independently to mount an efficient immune response .\nit is thought that the innate immune system protects the host from infection in a nonspecific way .\nthis , along with differences in cellular location likely serve to distinguish self - rna from nonself pamp rna , thus avoiding type i ifn induction in response to components of host nucleic acids . for example\n, tlr7 recognizes a specific motif within uridine - rich ribonucleotide sequences ( 25 , 26 ) , which are hypothesized to be unique to rna viruses .\ntlr9 recognizes dna pamp ligands and triggers signaling through the myd88 adaptor protein to induce type i ifn production ( 27 ) .\nthe recognition of nonself dna ligands by tlr9 might also be sequence dependent , and some studies have implicated the sugar - base - backbone sequence of pamp dna as a recognition factor ( 2830 ) .\nunlike tlrs , which are found either on the cell surface or within membrane - bound vesicles , rlrs are found in the cytoplasm where cellular rna is also present ( 1 ) .\nrig - i preferentially recognizes single - stranded rna ( ssrna ) over dsrna ( 15 , 31 ) .\nssrnas containing a terminal 5 triphosphate ( ppp ) , but not 5oh or a 5-methylguanosine cap , bind to the rig - i repressor domain and promote a conformational change that activates rig - i signaling ( 10 , 1316 ) .\nrna ligands of rig - i are longer than 23 nucleotides , have a linear structure , and contain a uridine- or adenosine - rich ribonucleotide sequence ( 3133 ) .\nhost mrna , trna , mirna , snrna , and rrna are not ideal rig - i ligands because their length , structure , 5 end modifications , and interactions with ribonucleoproteins limit their recognition .\nself - rnas therefore do not typically trigger innate immune programs or type i ifn expression ( 34 ) .\nmda5 triggers innate immune signaling in response to emcv infection and synthetic dsrna , such as poly i : c ( 11 , 20 ) .\nbut ssrna viruses such as dengue virus and west nile virus , as well as reovirus , a dsrna virus , have also been shown to trigger signaling partially via mda5 ( 12 , 35 ) .\nhowever , in these studies , mda5 appeared only to amplify type i ifn production as compared with rig - i , whose actions were essential to initiate innate immunity ( 12 ) .\n( 17 ) in this issue describes a plausible mechanism of rna ligand recognition by mda5 , providing new insights into the differential roles of rlrs .\nthe study reveals that mda5 binding to dsrna does not depend on its 5 end modification , but rather on its length .\ndsrnas with lengths of 2 , 3 , and 4 kb were shown to increasingly activate mda5 signaling , whereas rig - i recognized ssrna and , to a lesser extent , short dsrna motifs .\nthese results help explain how reovirus can trigger both rig - i and mda5 signaling .\nthe genome of reovirus comprises at least 10 segments of dsrna that vary in length , including long ( 3.9 kbp ) , medium ( 2.2 kbp ) , and short ( 1.2 kbp ) rna segments .\nshow that rig - i and mda5 recognize the short and long dsrna segments of the reovirus genome , respectively . in the case of emcv infection , the authors show that the viral genome forms long dsrna via its antisense replication intermediate , and this dsrna is recognized by mda5 but not by rig - i . on the other hand , vsv , which triggers rig - i dependent immunity , forms medium - length dsrna replication intermediates that are not recognized by mda5 .\npropose a model for pamp recognition by mda5 in which only long dsrna viral genomes or stable long duplex viral rnas formed during virus replication serve as mda ligands .\nthis model might explain why mda5 ignores self - dsrna , which is typically not present as long duplex rnas .\nthe current observations advance our understanding of how mda5 discriminates between potential rna ligands , but several questions about recognition of rna by rig - i and mda5 still remain .\nit is widely accepted that ssrna viruses generate dsrna during their replication process ( 36 , 37 ) . however , only mda5 recognizes emcv ( 8 kb ) , whereas rig - i recognizes other viruses with lengthy rna genomes , such as vsv ( 11 kb ) , jev ( 11 kb ) , and hepatitis c virus ( 9.6 kb ) .\nmda5 's failure to recognize these latter viruses may be due to their inability to form long or perhaps stable dsrna .\nit is also possible that recognition by mda5 depends on specific compartmentalization of the pamp rna with mda5 , as differences in the subcellular site of viral genome replication may influence the pamp \nthe mechanism by which mda5 discriminates between pamp ligands in terms of their length is also unclear .\ndemonstrate that mda5 binds long , capped , di- or mono-5 phosphate dsrna , whereas rig - i binds to short dsrna or 5ppp uncapped ssrna .\nwhen rig - i binds to 5ppp ssrna , it changes conformation , which disrupts the inhibitory interaction between the rig - i repressor domain and the cards .\nthis alteration results in the initiation of downstream signaling by the cards and exposes a 17- or 30-kd trypsin - resistant fragment corresponding to the rig - i repressor domain , thereby marking the activation of rig - i ( 10 , 15 , 16 ) . however , poly i : c binding to rig - i promotes a distinct conformational change that results in a 66-kd trypsin - resistant fragment , indicating that pamp - bound rig - i undergoes a distinct conformational change depending on the nature of its ligand .\nstructural studies validate that rig - i prefers ssrna ligands , whereas dsrna binds only inefficiently to rig - i , possibly due to constrains imposed by the location of basic residues within the rna binding groove of its repressor domain .\nthe charged residues are proposed to anchor 5ppp ssrna within the pocket , which would be less amenable to binding dsrna ligands ( 15 , 16 ) .\nthese observations suggest that rig - i may have two ways to distinguish different rna species : efficient recognition of 5ppp ssrna through its repressor domain ( 10 , 15 , 16 ) and comparably inefficient recognition and binding of dsrna ( 10 , 15 ) . by extension , these conformational alterations of rig - i might provide clues about how dsrna ligands interact with mda5 to stimulate its activation .\nthus , mda5 might become active upon binding long dsrna through a ligand - induced conformation change that places its card into a signaling - active conformation .\nthis might involve dsrna interactions with its helicase domain and c - terminal region in a fashion similar to the binding of poly i : c to rig - i .\nothers have demonstrated that although very short dsrna ( 2030 bp ) fail to trigger rig - i dependent signaling ( 15 , 17 ) , longer dsrnas ranging from 70 kb to 2 kb can at least weakly engage rig - i .\nthese data suggest that the length of dsrnas may dictate the interaction with the rig - i helicase domain and/or repressor domain in a manner that supports a rig - i dsrna complex .\nhowever , the mechanism of length discrimination of dsrna pamps by these rlrs has not yet been revealed .\nthe third rlr family member , lgp2 , has been defined as a regulator of rig - i signaling based on its suppression of rig - i function when overexpressed in cultured cells ( 10 , 38 , 39 ) .\nhowever , recent studies imply that lgp2 may also function as either a positive or negative regulator of rlr signaling by forming a heterodimer with rig - i or mda5 when bound to rna ligand ( 40 , 41 ) .\nsuch interactions between the rlrs may also broaden their pamp recognition profiles to accommodate other ligands , including ssrna or dsrna of varied length and composition , or even dna rna duplexes .\nstructure and function analyses of rna interactions with rlrs or heteromeric rlr complexes will further define the molecular basis of self- versus nonself discrimination .\nthe rlrs are adenosine triphosphate ( atp ) binding proteins that hydrolyze atp as a result of binding rna ligand ( 15 ) .\nhowever , the role of the atpase activity in the function of rlrs is not fully understood .\nrlrs contain multiple domains , including two domains known as the walker a motif and the walker b ( also known as the dexd / h - box ) motif , each located within the helicase domain ( 42 ) .\nwalker a and b motifs comprise an atp binding region wherein specific amino acid residues contact the -phosphate of the nucleotide and mediate atp hydrolysis upon substrate binding ( 4345 ) .\nmutant rig - i with an inactive walker a motif retains ssrna binding function but fails to trigger downstream signaling ( 15 , 46 ) .\nthus , atp hydrolysis is not essential for pamp binding but is required for downstream signaling .\nrecent studies revealed that the rig - i repressor domain , in addition to binding to the rig - i cards , forms a complex with the helicase domain linker region that likely stabilizes rna ligand binding ( 10 , 15 , 16 ) .\nmoreover , it seems that motifs in the rlr helicase domain could also be involved in rna substrate binding according to structure and function studies of other dexd / h - box rna helicases ( 42 ) .\nsuch studies indicate that the rna binding sites and the walker a and b motifs mediate specific interactions ( 47 ) .\nthese observations present a model in which a repressor domain helicase domain internal complex forms an rna binding pocket whose association with pamp rna may serve to initiate the atpase activity of rig - i , which then triggers a conformation change that allows innate immune signaling .\nthe repressor helicase domain interaction of rlrs may thus be the key determinant of pamp discrimination by rig - i and mda5 ( 15 , 17 ) .\nit also seems that rig - i atpase activity is involved in the unwinding of dsrna ( 15 ) .\nthe importance of this activity for innate immune function is unclear , but it might support rig - i interaction with dsrna ligands by catalyzing their conversion to ssrnas .\nthe breadth of prrs expressed in different cells and tissues and their distinct intracellular distribution provide the means for pamp detection and immune activation against a variety of microbial pathogens at the local site of infection or in the microbial niche . \nthese include the membrane - associated cytosolic replication sites of rna viruses , extracellular sites of microbe interaction , and endosomal sites of microbial trafficking and metabolism ( fig .\nthe recent identification of the dai ( dlm-1/zbp1 ) protein as a cytoplasmic sensor of microbial dna ( 48 ) suggests the existence of other prrs that detect cytosolic pamp dna .\nit is reasonable to speculate that , similar to tlrs and rlrs , the cytoplasmic dna sensor molecules also exhibit ligand specificity to cover a variety of dna pamps in association with their specific microbial niche , thus providing a further basis for self- versus nonself discrimination .\nunderstanding the processes of pamp ligand recognition within each microbial niche will provide a foundation for the design of appropriate vaccines , adjuvants , and immunotherapies .", "answer": "retinoic acid inducible gene ( rig)-i like receptors ( rlrs ) are cytosolic rna helicases that sense viral rna and trigger signaling pathways that induce the production of type i interferons ( ifns ) and proinflammatory cytokines . \n rlrs recognize distinct and overlapping sets of viruses , but the mechanisms that dictate this specificity were unknown . \n a new study now provides evidence for size - based discrimination of double - stranded rna ( dsrna ) by rlrs and suggests how host cells recognize a variety of rna viruses .", "id": 840} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmaternal moderate and severe anemia have been considered as conditions that affect adversely maternal and perinatal outcomes .\nfor such reason the identification of these cases is important since appropriate treatment may reduce the risk for adverse outcomes .\niron is the most common treatment currently used to control iron deficiency and anemia particularly in low - income countries , where anemia is more frequent .\nphysiologically , hemoglobin concentration drops during gestation , and for such reason the hemoglobin cutoff to define anemia was set at 11 g / dl of hb .\nmaternal hb levels are higher at high altitudes in all trimesters of pregnancy than at sea level .\nhowever , the reduction of hemoglobin levels during pregnancy occurs in populations at low and at high altitudes .\nthis is due to plasma volume expansion as a mechanism to improve arterial uterine flow to the placentae .\nthus , a normal hb value at first booking in the first trimester does not preclude the presence of anemia in a second measurement of hemoglobin as pregnancy advances .\na recent study showed a higher risk for anemia in pregnant women with low body mass index ( bmi ) .\n, anemia , particularly moderate and severe anemia is associated with high risk for low birthweight [ 3 , 9 , 10 ] , it is important to monitor hemoglobin values during pregnancy .\nthe present study has been designed to determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes .\nwe will determine rates of anemia , normal hemoglobin values and erythrocytosis ( hb > 14.5 g / dl ) .\nin addition , risk factors for moderate / severe anemia will be assessed in a multivariable analysis .\nthis is a secondary analysis of a large data base obtained from the perinatal information system in peru which includes 379,816 pregnant women and their babies obtained from 43 maternity units in peru .\ndata were obtained at the three geographical regions in peru : coast , highlands , and amazon .\nthe study was authorized by the institutional review board at the universidad peruana cayetano heredia .\nas the study used secondary analysis of data , the study was exempt from formal review . from the total sample size\n, a selection was made of all women diagnosed as nonanemic and without erythrocytosis at first booking ( hb ranging from 11 to 14.5 g / dl ) and having a second measurement of hemoglobin during the same pregnancy .\n, 57,231 pregnant women were living at low altitude ( < 2000 m ) , 11,349 women at moderate altitude ( 20003000 m ) , and 20,714 women were living at high altitudes ( > 3000 m ) .\ndata on gestational age at first and second hemoglobin measurement were recorded . with a second hemoglobin value , rates of pregnant women with anemia ( hb < 11 g / dl ) , normal hemoglobin values ( 1114.5 g / dl ) , and erythrocytosis ( hb>14.5 g / dl ) were determined . as demonstrated previously , no correction of hemoglobin cutoff to define anemia at high altitude is needed ; hence , the present study used the definition of anemia as suggested who for populations at sea level [ 1 , 11 ] .\nthe degrees of anemia were classified as mild ( hb 9.010.9 g / dl ) , moderate ( hb 7.0 < 9 g / dl ) , and severe ( hb < 7 g / dl ) . body mass index was calculated from prepregnancy body weight and height .\nlow bmi was defined as < 19.9 kg / m and high bmi as > 25 \naltitude was defined as low ( 01999 m ) , moderate ( 20002999 m ) , and high ( 3000 m ) .\nthe following perinatal outcomes were assessed : stillbirths , preterm deliveries and small for gestational age .\nstillbirths were diagnosed when fetal deaths occurred after 20 weeks of gestation or with a weight higher than 500 g. preterm births were defined as deliveries before 37 weeks of gestational age .\nsmall for gestational age was defined if birthweight was below the 10th percentile of the williams reference chart .\nthe adverse maternal outcomes assessed were preeclampsia , premature rupture of membranes ( prom ) , and postpartum hemorrhage ( pph ) .\npreeclampsia was defined as the presence of pregnancy - induced hypertension ( systolic pressure of 140 mm hg and/or diastolic pressure of 90 mm hg ) and proteinuria ( 300 mg/24 h ) after 20 weeks of gestation .\npph was defined as women after parturition with blood losses of 500 ml or more .\ndata are assessed according level of altitude ( low , moderate , and high ) and according to degree of anemia ( moderate / severe and mild ) , and erythrocytosis .\nif data were normally distributed , then a one - way analysis of variance were used ( anova ) .\ndata expressed in proportions were assessed by the chi - square test . the confidence interval ( ci )\nthe prevalences of women with moderate / severe anemia ( hb < 9 g / dl ) , mild anemia ( hb 910.9 g / dl ) , normal hemoglobin ( hb 1114.5 g / dl ) , and erythrocytosis ( hb > 14.5 g / dl ) were calculated for the total sample , as well as for groups at different altitudes ( low , moderate , and high altitude ) .\nestimates of crudes and adjusted odds ratio ( or ) with 95% ci were computed as measures of association between the variables .\na logistic regression analysis to determine the risk for moderate / severe anemia at second hemoglobin measured was assessed .\nthe estimates were adjusted for gestational age at second hemoglobin , hemoglobin value at first measurement , altitude , maternal age , body mass index , maternal education , marital status , prenatal care visits , parity , the presence of preeclampsia , cardiopathy , and diabetes .\nconcentration of hemoglobin at first booking in nonanemic women increased as altitude increased ( p < 0.05 ) , whereas birthweight decreased as altitude increased .\nno differences were observed in gestational age at birth at the three altitude groups studied .\nconcentration of hemoglobin at second measurement also was increased as altitude increases , but values were lower than those at first measurement , particularly at low altitude , in which values were reduced to 94% , whereas at moderate altitude . they were reduced to 98.4% and at high altitude to 99.2% .\ngestational age at first and second hemoglobin was higher as altitude of residence increased ( table 1 ) .\nmost of the studied sample remained with normal hemoglobin values at second hemoglobin measurement ( 75.1 ) .\nhowever , 21.4% of women became anemic at the second hb measurement . in all , 2.8% resulted with moderate / severe anemia and 3.5% with erythrocytosis ( figure 1 ) .\nwomen with anemia in the second hb measurement showed lower hb measurements in the first hb .\nconversely , women with erythrocytosis at the second hb measurement showed higher hb levels in the first measurement ( table 2 ) . in all cases hb was higher as altitude increased .\nthe rate of stillbirths was higher with moderate / severe anemia and with erythrocytosis ( p < 0.05 ) , which remained higher after controlling for confounders ( table 3 ) .\nthe rate of preterm births was increased in women with severe anemia ( 9.01% ; or = 1.81 ) . after adjusting for confounders , moderate / severe anemia ( or = 1.73 ) and mild anemia ( or = 1.28 ) were risks for preterm deliveries ( table 4 ) .\nthe rate of sga was significantly higher in mothers with erythrocytosis , almost twice , than in women with normal hemoglobin .\nlowest rate of sga was observed with a maternal hb level of 910.9 g / dl ( mild anemia ) ( table 5 ) .\nthe rate of preeclampsia was significantly higher in moderate / severe and mild anemia and in mothers with erythrocytosis , which remained after controlling for confounders ( table 6 ) .\nthe highest risk for pph was observed with moderate / severe anemia ( twenty times higher than in woman with normal hb levels ) ( table 8) .\nan increased risk for moderate / severe anemia was associated with higher gestational age at second measurement of hemoglobin , bmi < 19.9 kg / m , living without partner , prenatal visits care < 5 , first parity , multiparity , and preeclampsia .\nlower risk for moderate / severe anemia were observed with normal high hb level at first booking , living at moderate and high altitude , and with high bmi ( table 9 ) .\nthe present study has been designed to determine changes in hb levels after a first hb measurement in 89,294 pregnant women detected normality ( hb 1114.5 g / dl ) . according to the study results\nan increase in the rate of anemia according to pregnancy progress has been previously published in other settlings .\nmoderate / severe anemia has been characterized as the conditions more associated with maternal and perinatal adverse outcomes .\nour results demonstrated that 2.8% of women classified as nonanemic in the first hb measurement showed moderate / severe anemia in the second measurement .\nour data showed that moderate / severe anemia were associated with stillbirths , preterm births , preeclampsia , and pph .\nthe strength of this study is that it was done thanks to a large sample of women recorded through a perinatal information system that included 379,816 pregnant women and their newborn babies from different maternity units throughout peru .\nthis database is an important tool for monitoring conditions and trends related to pregnancies and newborns , including service characteristics and women 's risk factors .\ndata revealed that a percentage of women became anemic during the progression of pregnancy despite having a first normal hb measurement .\nthis is an important finding since moderate and severe anemia are harmful for mothers and neonates .\nrisks for moderate / severe anemia are preventable , or can be managed through appropriate management , such as with prenatal care , parity , preeclampsia , and low bmi .\nincreasing the number of prenatal visits will result in better monitoring of hemoglobin values , and can control or reduce the effect of preeclampsia .\nlow bmi is a characteristic of low - income countries and is associated with increased risk of maternal anemia , low birthweight , and preterm births .\nthe present results are in accordance with other studies where low prevalence of anemia was observed in women with highest bmi , and high prevalence of moderate / severe anemia were associated with malnutrition [ 14 , 15 ] .\nour data suggest that in situation in which a normal hemoglobin value was first observed in a woman with low body mass index , supplementation with iron should be recommended .\nit is interesting to note that populations living at moderate and high altitudes had lower risk for moderate / severe anemia in a second measurement of hemoglobin during pregnancy .\nthis suggests that women living in these altitudes bearing normal hemoglobin values at first booking should not be treated with iron supplementation . in recent years\n, it has been demonstrated that anemia defined as less than 11 g / dl of hb is lower at moderate and at high altitudes , since populations at these altitudes are characterized by increased hemoglobin values to compensate for the effect of altitudinal hypoxia [ 3 , 10 ] .\nhowever , we assumed that most cases of anemia were related to iron deficiency , which was supported by the finding that low bmi was associated with moderate / severe anemia .\nhowever , results of our analysis were similar to those obtained in a study in which bmi was obtained at first prenatal care .\nit is possible that erythrocytosis found in the second measurement of hb after a normal value of hb at first booking could be due to the effect of iron supplementation , since in peru a ministry of health regulation orders pregnant women be supplemented with iron .\nhowever , low adherence may explain the low prevalence of erythrocytosis in a second hb measurement during pregnancy .\nthe results of this study confirm that prevalence of anemia increases as pregnancy progresses and that a normal value at first booking should not be considered sufficient , as further hb values should be indicated and observed during the course of pregnancy .", "answer": "objective . to determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes \n . methods . \n this is a secondary analysis of a large database obtained from the perinatal information system in peru which includes 379,816 pregnant women and their babies from 43 maternity units in peru \n . results . \n most women remained with normal hemoglobin values at second measurement ( 75.1% ) . \n however , 21.4% of women became anemic at the second measurement . \n in all , 2.8% resulted with moderate / severe anemia and 3.5% with erythrocytosis ( hb>14.5 g / dl ) . in all cases \n hb was higher as altitude increased . \n risk for moderate / severe anemia increased associated with higher gestational age at second measurement of hemoglobin , bmi < 19.9 kg / m2 , living without partner , < 5 antenatal care visits , first parity , multiparity , and preeclampsia . \n lower risk for moderate / severe anemia was observed with normal high hb level at first booking living at moderate and high altitude , and high bmi . \n conclusion . \n prevalence of anemia increases as pregnancy progress , and that a normal value at first booking may not be considered sufficient as hb values should be observed throughout pregnancy . \n bmi was a risk for anemia in a second measurement .", "id": 841} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the outpatient setting , actinic keratosis is one of the most commonly treated skin conditions , the prevalence of which increases with cumulative skin exposure and increasing age .\nrates of 1125% have been reported in the northern hemisphere and of 4060% in australia .\nactinic keratoses are strong predictors of squamous cell carcinomas and are believed to be precursors of squamous cell carcinomas of the skin .\na number of studies have been published recently concerning modalities of photodynamic therapy ( pdt ) treatment for actinic keratosis in which the efficacy of several photosensitisers and/or light sources were compared , , , .\nthe most recent of these is the study by dirschka and colleagues which appeared recently in the british journal of dermatology and in which a gel formulation of 5-aminolaevulinic acid ( bf-200 ala ) was found to be superior to methyl-5-aminolaevulinate ( mal ) . in the same study ,\nthe narrow - band light sources were found to be more effective than the broad - band light sources , although the narrow - band sources were associated with a higher occurrence and severity of adverse effects , which included pain , burning , erythema and exfoliation , irrespective of the photosensitizer used .\nwhile such a multicenter , randomized study is to be commended , the authors in our opinion failed to appropriately consider their findings in the light of previous studies , since a number of pertinent and highly relevant articles were not mentioned .\nan important study in this context is the study by von felbert and colleagues with a longer follow - up time of 12 months ( compared to 12 weeks in the study of dirschka et al . ) and in which the use of narrow - band and broad - band sources were found to be equally effective .\none reason given by von felbert and colleagues for the comparable efficiency of these sources was the use of a more advanced and efficient broad - band optical filter ( in comparison to the broad - band sources used in previous studies ) .\nhowever , not only failed to discuss reasons for the differences between the narrow - band and broad - band types of sources used , but also did not comment on the differences found between the various types of broad - band sources employed . additionally , despite the findings of von felbert et al . who found the use of a broad - band source with water filter to be associated with less pain than that caused by a narrow - band source , and a study by apalla et al . who found the use of a broad - band source without a water filter to be associated with pain , dirschka and colleagues did not consider the fact that broad - band sources would result in absorption over a broader spectral range ( and possibly encompassing several maxima ) of the photosensitizer as has been discussed previously\nadditionally , previous studies in which no differences were found between narrow- and broad - band sources , , were not considered .\ntheir study also demonstrated that the conditions under which pdt was applied had a pronounced impact on the efficiency of the treatment .\nfor mal , the von felbert study also found considerably higher response rates ( 80% total clearance ) as compared to the dirschka et al . \npossible reasons for such a pronounced difference between the response rates in these two studies were however not discussed by dirschka and colleagues . while the extent of pain experienced during photodynamic therapy ( which is deemed to be the main side - effect of pdt , ) was documented by dirschka et al . , possible reasons for the greater incidence of pain during the use of the narrow - band sources were not considered . in the dirschka et al .\nstudy , a comparison of the photosensitizers used showed bf-200 ala to be superior to mal , but again , a study with contradictory findings ( gholam et al . ) is not discussed .\nwhile we do not wish to infer that the study performed by dirschka and colleagues is in any way erroneous , we would nevertheless like to point out that the discussion of the results and the authors selection of cited literature appears to be biased towards studies supporting the authors own findings .\nthe problem of such a bias has recently been outlined , together with the need for an up - to - date selection of literature and the recommendation that a concealment of contradictory or critical literature should be avoided .\nas a result of the rather selective choice of literature provided and the lack of a thorough consideration of the relevant studies already published , the article by dirschka and colleagues leaves a number of questions unanswered .\nfurthermore , the corresponding editorial published in the same issue of the british journal of dermatology is unfortunately also based on the acceptance of the superiority of bf-200 ala in comparison to mal as well as the superiority of narrow - band in comparison to broad - band sources and fails to address the fact that several other studies have found contradictory results .\ncertainly , sweeping statements claiming e.g. , narrow - band sources to be preferable to broad - band sources or bf-200 to be better than mal should not be made on the basis of a single study , especially since such statements may lead to rapid and ungrounded propagation of therapeutic protocols . in conclusion\n, it would appear that the last word concerning the optimal photosensitizer and radiation source for the treatment of actinic keratosis has not yet been spoken .\ntherapy for actinic keratosis should be a carefully chosen compromise between undesired side - effects and therapeutic efficacy and needs to be based on a consideration of all of the relevant clinical studies .", "answer": "actinic keratosis is one of the most commonly treated skin conditions . \n a number of studies have recently been published on the treatment of this ailment using photodynamic therapy . \n the authors of this letter are concerned about the interpretation of some of these studies and would like to outline possible misinterpretations which may arise due to an incomplete analysis of the study reports available . \n clearly , the ideal therapy for actinic keratosis should be a carefully chosen compromise between undesired side - effects and therapeutic efficacy and needs to be based on a consideration of all of the relevant clinical studies .", "id": 842} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin march 2013 , cases infected with a novel reassortant avian - origin influenza a ( h7n9 ) virus emerged in china and had high mortality . that month\n, a patient with h7n9 influenza was admitted to our hospital , and daily lung ultrasound was performed . a 54-year - old woman , who ran a convenience store beside a poultry market , complained of cough and high fever for 4 days .\nher temperature was 38.6c , and she had a heart rate of 113 beats per minute and a respiratory rate of 26 breaths per minute .\nher white blood cell count was 2.7 10/l , and neutrophil , lymphocyte , and monocyte levels were 72.4% , 22% , and 5.2% , respectively .\nher partial pressure of oxygen in arterial blood was 72 mm hg , and her fraction of inspiratory oxygen ( fio2 ) was 40% .\navian - origin influenza a ( h7n9 ) virus was confirmed from the pharyngeal swabs by real - time reverse transcriptase - polymerase chain reaction .\ntreatment with oseltamivir ( 150-mg capsule taken by mouth twice a day ) was initiated , and she was admitted to an isolated room in the infectious diseases department .\nbothell , wa , usa ) with c60 convex probe ( 2 to 5 mhz ) was performed , and the lung ultrasound score ( lus ) was recorded , and both effectively reflected the progression of pneumonia ( figure 1 ) .\ndynamic changes of chest computed tomography ( ct ) , radiography , and lung ultrasound in a patient with h7n9 influenza .\n( a - c ) ct showed pneumonia in the left upper lung , with partial consolidation on admission .\n( d - f ) lung ultrasound corresponding to ct in ( a - c ) showed multiple abutting b2 lines , and some regions presented a tissue pattern ( arrow ) .\n( g - i ) ct on day 6 after admission showed that the pneumonia was partially absorbed .\n( j - l ) lung ultrasound corresponding to ct in ( g - i ) showed that the number of b lines was obviously decreased , and the consolidation disappeared .\n( m - o ) ct on day 9 after admission showed that the size of the lesion was obviously reduced .\n( p - r ) lung ultrasound corresponding to ct in ( m - o ) indicated that only the a line and few b lines were visible .\n( s - u ) chest radiography on days 1 , 3 , and 6 after admission showed no obvious change of the pneumonia .\n( v ) dynamic changes of lung ultrasound score ( lus ) ( total of 48 for normal lung ) .\nthe onset of h7n9 influenza in this case was manifested by hyperpyrexia and flu - like symptoms and progressed to lobar pneumonia 4 days later .\nchest radiograph is the routine tool for assessment of pneumonia , but its sensitivity and accuracy were not so good .\nct is regarded as the gold standard , but its application is limited in cases with this new emerging virus since strict protection should be followed to avoid person - to - person transmission .\nultrasound has many advantages , including convenience , rapidness , non - invasiveness , availability for repeated examination , and absence of radiation .\nthe right lung presented an a line with few isolated b lines , whereas the left lung presented multiple abutting b lines and consolidation . when the patient improved , both b lines and the area of consolidation were decreased and the lus was synchronously increased .\nthis case highlights that ultrasound can be an adjutant to chest radiography and ct in caring for patients with h7n9 influenza .\nwritten informed consent was obtained from the patient for publication of this letter and accompanying images .", "answer": "h7n9 influenza is a new emerging infection and has high mortality . \n both chest radiography and computed tomography ( ct ) had some limitations in assessing such patients . \n we performed daily lung ultrasound in a patient with h7n9 influenza . \n lung ultrasound and lung ultrasound score showed high consistency with ct and the progression of pneumonia . \n ultrasound can be adjutant to chest radiography and ct in caring for patients with h7n9 influenza .", "id": 843} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nphlegmon is a spreading diffuse inflammatory process associated with the formation of a suppurative exudate or pus .\nphlegmonous infection may involve any gastrointestinal tract site , although the stomach is most frequently involved ( 1 ) . however , phlegmonous involvements of the esophagus , small bowel , or colon are rare ( 1 - 3 ) .\ntherefore , strong suspicion and recognition of this disease is a key to the diagnosis and prompt management of patients with acute symptoms .\nhowever , the role of surgery has been questioned for the diffuse disease form ( 2 ) .\nthe authors report a rare case of acute diffuse phlegmonous esophagogastritis . in this case , proper radiologic diagnosis with typical chest computed tomography ( ct ) findings ( 4,5 ) enabled appropriate treatment and timely surgical intervention .\na 48-yr - old man presented with left chest pain , abdominal pain , and dyspnea of three days duration .\nfive days before admission , he had been involved in a minor motorcycle accident , but was asymptomatic for two days .\nhowever , his vital signs were stable ; heart rate 70/min , respiration 37/min , blood pressure 110/80 mmhg , and body temperature 36.8. a physical examination also revealed no remarkable finding with normal bowel sounds and a soft , flat abdomen with no general or rebound tenderness .\nlaboratory tests revealed ; wbc 3,200/l , c - reactive protein 31.68 mg / dl , and serum glucose 201 mg / dl , and chest radiography on admission showed mediastinal widening and bilateral pleural effusion ( fig .\nthe patient underwent endoscopy on the admission day to exclude esophageal rupture , and diffuse thickening of mucosal folds with decreased distensibility and an 1 cm sized mucosal ulcer in upper thoracic esophagus were observed with scattered patches of hemorrhage in the gastric mucosa of the body and antrum . on the evening of first hospital day , the patient was became febrile with a body temperature of 39 , and thus , empirical treatment with broad spectrum antibiotics was immediately started under the suspicion of empyema or secondary infection . on the second hospital day ,\nthe dyspnea worsened and the amount of left pleural effusion increased on chest radiography . left closed thoracostomy was performed with pus drainage . on the forth hospital day ,\na contrast - enhanced chest ct scan was performed and showed diffuse and marked circumferential wall thickening of the entire thoracic esophagus , extending to gastric cardia and associated with diffuse intramural low density and a peripheral enhancing rim ( fig .\na ct diagnosis of acute phlegmonous esophagogastritis was suggested and bilateral open thoracotomies were performed immediately .\npleural fluid analysis revealed exudates and a surgery was decided due to worsening of clinical condition of the patient and radiologic findings . during surgery\n, bilateral multiloculated pleural effusions were evacuated through open thoracotomies and the esophagus was freed from adjacent tissue .\nthe adventitial and muscular layers of the esophagus were intact and no perforation was identified .\nseveral separate esophageal myotomies were performed and the submucosal layer was found to have been filled with thick , cheesy materials , which were removed from the mucosa by scraping .\nblood and sputum cultures of the patient and a microbiologic examination of pleural fluid demonstrated klebsiella pneumoniae .\na follow - up chest ct scan performed on the 49th postoperative day showed reduced diffuse esophageal wall thickening and bilateral pleural effusion ( fig . 2c ) .\nphlegmonous infection can affect any site of the gastrointestinal tract , although the stomach is most frequently involved ( 1 - 3 ) .\ninvolvements of other sites have been rarely reported , but the simultaneous involvement of esophagus and stomach has only been reported in a very limited number ( 1 , 2 ) .\nphlegmonous infection usually involves the submucosa and not the mucosa ( 1 - 3 ) .\ndiffuse esophagogastric involvement of phlegmonous inflammation was evident in our case by chest ct and during surgery . in its localized form , an area of acute inflammation in submucosa\nphlegmonous infection may also present as a mass in the gastric wall ( 6 ) .\nthe inflammation produced may involve the muscularis mucosa and the serosa , and lead to perforation or even peritonitis ( 1 ) . in its diffuse form\n, phlegmonous infection can involve the entire stomach , but it rarely extends beyond the cardia or pylorus ( 6 ) .\nreported predisposing factors ( 4 ) include immune suppression , alcoholism , peptic ulcer disease , chronic gastritis or some other gastric mucosal injury , achlorhydria , infection , connective tissue disease , and malignancy .\npresumably , these conditions predispose the stomach to infection by eliminating various defense mechanisms , such as , inherent gastric cytoprotection or the bactericidal effect of gastric acid ( 1 , 6 ) .\nnevertheless , approximately 50% of reported cases were previously healthy and had no significant anteceding risk factors ( 6 ) .\nwe consider that uncontrolled diabetes mellitus and a recent history of chest trauma in combination with excessive alcohol consumption played an important role in the development of the disease in our patient .\nhistopathologically , the submucosa is thickened and infiltrated by neutrophils and plasma cells with intramural hemorrhage , necrosis , and thrombosis of submucosal blood vessels ( 1 ) .\nthe most common pathogens are streptococcus species , staphylococcus species , escherichia coli , haemophilus influenzae , proteus , and clostridia ( 6 ) .\nstreptococcus accounts for approximately 70 to 75% of cases , and it is also the organism most commonly associated with death caused by phlegmonous gastritis .\nthe causative pathogen of phlegmonous infection in our patient is believed to be klebsiella pneumoniae , based on positive culture results on blood , sputum and pleural fluid .\nphlegmonous gastritis has rarely been diagnosed before surgery , because it is seldom considered in the differential diagnosis of an acute abdomen ( 3 ) .\nother symptoms include nausea , vomiting , hematemesis , hiccups , prostration , and fever ( 6 ) . on the other hand , when the esophagus is involved , odynophagia , dysphagia , and chest pain are the most common symptoms ( 1 ) .\nphlegmonous infection is usually diagnosed at surgery or at autopsy ( 3 ) , and because there are no pathognomonic signs or symptoms , phlegmonous gastritis is rarely diagnosed before surgery .\nendoscopy of the affected esophagus shows diffuse luminal narrowing with poor distensibility and ulcer - like lesions ( 3 ) .\nendoscopic ultrasonography ( eus ) findings in previous case reports were diffuse thickening with hypoechoic lesions in the submucosal layer ( 1 , 6 ) . the endoscopic examination of our patient also revealed similar findings of diffuse mucosal fold thickening , a mucosal ulcer in the upper thoracic esophagus , and scattered hemorrhagic patches in gastric mucosa . the reported ct findings of acute phlegmonous esophagitis or gastritis include diffuse esophageal and stomach wall thickening with circumferential intramural low attenuation surrounded by a peripheral enhancing rim .\nthe intramural low attenuation represents severe inflammation and abscess localized to the submucosa and muscularis layer ( 4 , 5 ) . within the thickened wall ,\ncontrast - enhanced chest ct in our patient showed findings typical of acute phlegmonous inflammation with simultaneous esophageal and stomach involvement .\nthe radiographic differential diagnoses included a dissecting intramural hematoma and tubular duplication of esophagus and emphysematous esophagitis or gastritis ( 5 , 7 ) .\nhowever , the clinical symptom of a dissecting intramural hematoma is chest pain with no evidence of infection or inflammation , and patients with tubular duplication are likely to have no symptoms or signs .\nthe overall mortality of phlegmonous gastritis in a review of 36 reported cases was 42% , and the mortality rates of the 10 patients that underwent surgical resection as compared with the 26 patients treated conservatively were 20% ( 2/10 ) and 50% ( 13/26 ) , respectively ( 6 ) . during the last 50 yr , some reports have described patients with phlegmonous gastritis successfully treated with medical therapy alone .\noverall , the mortality rate for patients with medially treated localized disease was 17% , whereas that for diffuse disease was 60% .\nthus , antibiotic therapy and surgical drainage are effective treatments for acute phlegmonous esophagitis depending on the clinical situation ( 1 , 3 , 8) . in cases of phlegmonous esophagogastritis ,\nprotracted conservative treatment result in surgical resection due to the possibilities of esophageal necrosis , esophageal stricture , gastric mucosal atrophy , and complicated peritonitis ( 1 , 8 , 9 ) .\nour patient was initially treated with broad spectrum antibiotics and left closed thoracostomy with empyema drainage .\nhowever , surgical intervention was decided upon due to a worsening of his condition , the duration of his clinical symptoms , and radiographic findings , which included a proper ct diagnosis of acute phlegmonous esophagogastritis .\nwe consider that combined medical treatment and timely surgical intervention played an important role in the cure achieved in our patient , who experienced no major post - operative complications . in conclusion , although acute phlegmonous esophagogastritis is rare and a preoperative diagnosis is difficult , awareness of this disease entity and prompt diagnosis based on typical chest ct findings are major key factors to successful treatment .", "answer": "acute phlegmonous infection of the gastrointestinal tract is characterized by purulent inflammation of the submucosa and muscular layer with sparing of the mucosa . \n the authors report a rare case of acute diffuse phlegmonous esophagogastritis , which was well diagnosed based on the typical chest computed tomographic ( ct ) findings and was successfully treated . a 48-yr - old man presented with left chest pain and dyspnea for three days . \n chest radiograph on admission showed mediastinal widening and bilateral pleural effusion . \n the patient became febrile and the amount of left pleural effusion is increased on follow - up chest radiograph . \n left closed thoracostomy was performed with pus drainage . \n a ct diagnosis of acute phlegmonous esophagogastritis was suggested and a surgery was decided due to worsening of clinical condition of the patient and radiologic findings . \n esophageal myotomies were performed and the submucosal layer was filled with thick , cheesy materials . \n the patient was successfully discharged with no postoperative complication .", "id": 844} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrasmussen 's aneurysm is a less frequently noticed entity usually associated with pulmonary tuberculosis presenting with massive hemoptysis due to involvement of small peripheral pulmonary or bronchial artery by the tubercular cavity or lesion .\ninvolvement of a large central pulmonary artery by metastatic mediastinal nodal lesions is unreported so far . despite the large size ,\na 65-year - old male of primary squamous cell carcinoma left buccal mucosa treated by left composite resection , and modified radical neck dissection 8 months back .\npostsurgery local radiation with 25 fractions of 2 grey ( gy ) each completed just 4 months before , presented with generalized weakness and pain right hip region .\nthere was no history of fall , fever , loss of weight or bleeding from any site .\nclinical examination revealed no evidence of disease at the local site and no palpable masses anywhere in the body and there was no neurological deficit .\nhematological , bio chemical and metabolic parameters were within normal limits , except mild hypo chromic normocytic anemia .\ninitial imaging with magnetic resonance imaging of lumbo sacral spine revealed t1 hypointense and t2 hyperintense signal intensities in right sacral ala and iliac bone lesions suggestive of metastatic lesions .\npatient was subjected to fluorine 18-fluoro deoxy glucose positron emission tomography / computerized tomography ( f18-fdg ) for restaging and further evaluation .\nthe primary site of left buccal region showed postoperative status with no morphological or metabolic abnormality .\nthere was a metabolically active enhancing nodular mass lesion on the dorsum of the tongue measuring 30 19 mm with a standardized uptake value maximum ( suv max ) of 5.77 [ figure 1a ] , similar nodular deposit in the cervical nuchal muscle measuring 22 21 mm with an suv max of 4.82 [ figure 1b ] .\nthere were multiple bilateral metabolically active necrotic , nodular , sub pleural and parenchymal pulmonary metastasis with associated mild degree pneumothorax [ figure 2 ] .\nmediastinum showed multiple metabolically active enlarged lymphadenopathy encompassing bilateral hilar , sub aortic , and para aortic lymphadenopathy which also showed conglomeration and central necrosis .\ninterestingly there was a large contrast filled cavitary area measuring 66.6 54.8 72.6 mm seen amidst the necrotic lymph nodal mass , devoid of any fdg avidity [ figure 3 ] . on close scrutiny\nthe radiographic contrast collection was traceable up to one of the adjoining first order branch of left pulmonary artery [ figure 4 ] .\nthere were multiple metabolically active mixed lytic sclerotic disseminated skeletal metastasis as well [ figure 5 ] . due to his poor physical condition and the extensive disease load .\nsmall asymptomatic unilateral pneumothorax requiring no intervention and the large extravasated contrast being restricted within the confines of the cavitating nodal metastasis explaining the stark absence of hemoptysis , patient was managed conservatively without any active intervention shifting from a curative to palliative intent .\n( a ) metabolically active enhancing nodular mass lesion on the dorsum of the tongue ( dotted arrow ) .\n( b ) metabolically active nodular deposit in the cervical nuchal muscle ( thick arrow ) axial positron emission tomography / computerized tomography images of chest showing multiple bilateral metabolically active sub pleural and parenchymal pulmonary metastasis ( arrows ) with associated left sided pneumothorax ( dotted arrow ) axial positron emission tomography / computed tomography images of chest showing multiple metabolically active enlarged mediastinal lymphadenopathy with conglomeration and central necrosis ( arrows ) and a contrast filled cavitary area amidst the necrotic lymph nodal mass devoid of any fluoro deoxy glucose avidity ( dotted arrow ) high resolution axial and coronal computerized tomography chest showing the radiographic contrast collection traceable up to one of the adjoining first order branch of left pulmonary artery ( arrow ) maximum intensity projection and coronal positron emission tomography/ computerized tomography images revealing multiple metabolically active mixed lytic sclerotic disseminated skeletal metastasis ( arrows )\nerosive pseudo aneurysm of small caliber pulmonary arterial branch caused by an adjoining infiltrating pulmonary lesion is termed as rasmussen aneurysm .\nfritz waldemar rasmussen a 19-century danish physician first described the occurrence of dilation of the pulmonary artery in a tuberculous cavity , rupture of which causes hemorrhage and hemoptysis , often massive and life threatening .\nother documented causes are atherosclerosis , bronchiectasis , sarcoidosis , trauma , postcardiac catheterization and postnecrotizing pneumonias .\npathogenesis implicated is the progressive weakening of pulmonary arterial wall adventitia and media by granulation tissue , resulting in thinning of the arterial wall and formation of pseudoaneurysm .\nthe distribution is usually peripheral and beyond the branches of main pulmonary arteries . in the present era of selective catheter angiography , the entity of rasmussen 's aneurysm\nis a retrospective detection encountered while addressing suspected bronchial artery erosion being the cause of massive , intractable and life - threatening hemoptysis .\nangiographic intervention is warranted to unearth the source of bleeding and simultaneously attempt to embolize the bleeding source from rasmussen 's transformed culprit artery .\nour patient had extensive metastasis to skeleton , lungs , muscles , tongue and mediastinal adenopathy with significant necrosis .\none of the aggressive and necrotizing lymphnodal mass has eroded the adjoining pulmonary artery branch , in this case a major branch vessel unlike smaller vessels usually seen in tuberculosis cavities .\nthe leaked out blood was contained within the necrotic lymph nodal mass which explains the absence of any revealed hemoptysis and a possible emergency bleeding situation despite the large sized extravasation .\nconventional sites of aneurysm are peripheral and beyond the branches of main pulmonary arteries , however it was central in this case and involved a larger central pulmonary arterial branch .\nreported cases of rasmussen 's aneurysm are the result of infective and chronic tuberculous cavity eroding the adjoining small caliber bronchial / pulmonary artery and none by an aggressive metastatic necrotic nodal mass .\nthe case also highlights the aggressive , extensive and erosive nature of squamous cell carcinoma metastasis .\nrasmussen 's aneurysm is a rare sequel of pulmonary tuberculosis presenting with massive hemoptysis usually involving a small peripheral pulmonary or bronchial artery .\ninvolvement of a large central pulmonary artery by an aggressive necrotizing mediastinal lymph nodal mass is unreported so far .\nour case is one such entity of this rarity with walled off collection of a large magnitude contained within the necrotic mass and nonhemoptytic manifestation being an additional associated rarity .", "answer": "the authors report an extremely rare occurrence of a massive aneurysm of a major pulmonary artery branch vessel caused by adjacent necrotizing aggressive squamous cell carcinoma metastatic mediastinal nodes . despite the huge size \n , there was no hemoptysis due to the walling off effect by the necrotic nodes .", "id": 845} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncongenital bochdalek hernia ( cbh ) develops as a result of the inappropriate fusion of the pleuroperitoneal fold and septum transversum at the site of the posterolateral lumbocostal trigone at the sixth week of gestation .\nthis entity was first described by mccauley in 1754 and then by vincent alexander bochdalek in 1848 .\nthis type of diaphragmatic hernia is considered a perinatal disease that presents a few hours after birth , or in early infancy , and it is associated with significant morbidity and mortality .\ncbh in adults is very rare ; it remains asymptomatic until adulthood and generally presents with thoracic and/or abdominal symptoms aggravated in supine position .\nwe present a case of left - sided congenital bochdalek hernia that remained asymptomatic and was discovered incidentally during secondary cytoreductive surgery for epithelial ovarian cancer ; in this patient , a iatrogenic diaphragmatic defect was found , hyperthermic intraperitoneal chemotherapy ( hipec ) was performed and early postoperative bilateral anterior thalamic infarction developed .\na 46-year - old female patient with a bmi of 25 was referred to our tertiary center ( cerrahpasa medical faculty , gynecological oncology unit ) in august 2016 with the diagnosis of platinum - resistant ovarian cancer .\npositron emission tomography and computed tomography ( ct ) revealed implants on the right diaphragmatic surface after first - line adjuvant chemotherapy . she has never had any thoracic or abdominal symptoms and no history of major trauma . initial preoperative evaluation of the patient revealed no significant sign of diaphragmatic hernia .\nher physical examination was normal , including chest auscultation sounds and chest x - ray .\nthoracic ct did not reveal any abnormal image that could be evaluated as a diaphragmatic hernia .\nshe was placed in flank position , and , under general anesthesia , laparotomy was performed .\nan oval defect with the dimensions of 3 4 cm was seen in the left posterolateral site of the diaphragm ( fig .\nthe most distal portion of the inferior lobe of the left lung was visible through the defect during inspiration and expiration movements .\ndrainage chest tubes were inserted bilaterally via the 6th intercostal spaces to avoid leakage of the chemotherapeutic agents across repaired diaphragm and postoperative massive pleural effusion .\nthe tissue around the congenital left - sided defect was excised circularly and the defect itself was repaired with interrupted nonabsorbable monofilament sutures .\nafter complete cytoreduction had been achieved , hyperthermic intraperitoneal chemotherapy with doxorubicin 35 mg / m and paclitaxel 175 mg / m for 60 min at 42.5c was delivered .\nno leakage via drainage tubes from the thoracic cavity was noted during the procedure . during the surgery ,\nthe patient was managed by standard monitoring , which involved continuous monitoring of electrocardiography , invasive blood pressure , central venous pressure , pulse oximetry , body temperature and hourly urine output .\narterial samples were drawn at regular periods for the determination of electrolytes , acid base status and hematocrit .\nfinally , the operation lasted 4 h. at the end of the surgery , the patient remained intubated and was transferred to the intensive care unit for monitoring ongoing resuscitation along with fluid and electrolyte management .\nthe patient was extubated 10 h after completion of surgery , and was transferred to the service on the 2nd postoperative day .\nprophylactic enoxaparin 4,000 iu was started 6 h after surgery . on the 3rd and 4th postoperative day , excessive sleepiness throughout the day and dyspraxia was noted . bilateral anterior thalamic infarction caused by emboli that block the thalamosubthalamic artery\nthe dose of enoxaparin was changed from 4,000 iu once a day to 800 iu twice a day .\nfollow - up at 4 months after surgery showed no evidence of recurrence and no symptom regarding thalamic infarct .\ncbh generally presents in newborns with severe respiratory failure or in infancy due to herniation and/or strangulation of the abdominal contents .\none of the best studies concerning the incidence of the defect in adults was carried out by mullins et al . , who reviewed 13,138 ct scans .\ntheir study revealed an incidence of 0.17% , with 68% being right - sided defects and 77% of the patients being female .\nsince the second study summarized symptomatic cases , demographics identified were different than those in asymptomatic ones .\nthis difference showed that more cases of right - sided cbh in females may remain silent than left - sided cases .\nthese data were supported by several case reports . nevertheless , in our case , the defect was noted on the left side . also , no herniation of intestinal loops was noted , and the patient has never had any thoracic or abdominal symptom that might be related to diaphragmatic hernia .\ndiagnosis of the disease might be carried out by chest ct when there are clinically unexplained thoracic and abdominal symptoms .\nthe chest ct of our patient did not reveal any of the above - mentioned patterns .\nthere are several cases concerning surgical repair of the defect both laparoscopic , via laparotomy , and through the thoracic cavity .\nwe performed upper midline incision for laparotomy , and there was no need for another access to carry out the repair of the diaphragmatic defect .\nrepair of diaphragmatic defect can be performed by various techniques , using absorbable or nonabsorbable sutures in an interrupted or continuous fashion . from our point of view\n, surgeons may choose any of them provided that they are comfortable with the procedure .\nthe main reason for using bilateral chest tubes was to prevent massive pleural effusion due to hipec .\nin addition , intra - abdominal pressure increases during hipec , which may subsequently cause a cephalad shift of the diaphragm to increase peak airway pressures and reduce residual capacity .\nchest drains which were inserted prior to hipec reduce the increase in peak airway pressure , and by this way , the length of the intubation period and hospital stay can be decreased .\nmalignancy itself , hipec , central venous cannulation , the position of the patient 's neck , sudden blood loss and a long duration of the operation were noted as possible risk factors in our case . in conclusion , although congenital bochdalek hernia commonly occurs in the newborn and infancy period , it must not be excluded in the case of unexplained abdominal and/or thoracic symptoms in adults . despite the fact that this kind of rare condition presents with pain , obstruction symptoms or pulmonary symptoms , it can be silent until discovered incidentally .\nsecondly , cerebral embolism should be suspected in the presence of any neurological symptom in postoperative patients .", "answer": "congenital bochdalek hernia is a defect of the diaphragm and very rare in adults . \n only around 100 cases have been reported in the literature . herein , we present a case with a recurrent ovarian cancer who underwent secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy . \n an oval defect with dimensions of 3 4 cm was seen in the left posterolateral site of the diaphragm during surgical exploration . \n in addition , a 6 3 cm iatrogenic right - sided diaphragmatic defect was found and repaired . in the early postoperative period , \n a bilateral thalamic infarction occurred .", "id": 846} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n\n crestal incision placed about 1.5 mm palatal to the greatest bony height with an angulation of 45 with no .\n15 bard parker blade [ figure 1 ] \n a vertical releasing incision placed mesially and distally to the crestal incision without disturbing the adjacent teeth papilla and extending about 3 mm labially [ figure 2 ] \n soft tissue reflected to expose the cover screw [ figure 3 ] \n palatal extension of the incision followed closer to the adjacent teeth on both sides , and a release incision made around the palatal portion of the exposed cover screw [ figure 4 ] \n then healing abutment is placed after thoroughly cleaning the soft tissue around internal hex of the implant [ figure 5 ] \n soft tissue approximated with 40 suture material ( vicryl)sutures removal has to be done after 10 daysafter 2 weeks , second stage prosthetic procedure should be carried out . \n \ncrestal incision placed about 1.5 mm palatal to the greatest bony height with an angulation of 45 with no .\n15 bard parker blade [ figure 1 ] \n a vertical releasing incision placed mesially and distally to the crestal incision without disturbing the adjacent teeth papilla and extending about 3 mm labially [ figure 2 ] \n soft tissue reflected to expose the cover screw [ figure 3 ] \n palatal extension of the incision followed closer to the adjacent teeth on both sides , and a release incision made around the palatal portion of the exposed cover screw [ figure 4 ] \n then healing abutment is placed after thoroughly cleaning the soft tissue around internal hex of the implant [ figure 5 ] \n soft tissue approximated with 40 suture material ( vicryl ) sutures removal has to be done after 10 days after 2 weeks , second stage prosthetic procedure should be carried out . incision and flap outlined ( after reflection )\nmore importantly it plays an important and crucial role in an esthetic component of a natural dentition .\nhence , it is very vital to maintain the integrity of the papilla during second stage implant surgery .\nseveral methods with unique incisions and suturing designs have been proposed to regenerate interdental papilla around implants .\npalacci suggested that a full thickness flap be raised from the buccal and palatal side of the implant on the ridge and rotated 90 to accommodate the interproximal space of the implant .\npalatal sliding strip flap to form papilla between implants and natural dentition in the anterior maxilla .\nnemcovsky et al . suggested an u- shaped incision , with opening toward the buccal aspect of the implant site with divergent incisions .\ntinti and benfenati reported a ramp mattress suture design , which pulled the buccal flap coronally , to obtain a papilla between two implants .\nsuggested a split finger surgical method in which three interlacing finger like incisions were made and each of the fingers was sutured over the desired interdental papillary position .\nproposed a method for papilla regeneration wherein the healing abutment is buried beneath the gingival flap to produce a dead space with expectation of the space being filled by the soft tissue . even though these procedures provided papillary height , the results were not predictable .\nvarious factors were involved in the success of any papilla regeneration procedures , such as preservation of blood supply , prevention of scar formation , and more importantly ideal placement of the implant into the bone .\nthis new and innovative surgical technique provided significantly excellent results compared to the conventional mid - crestal technique [ figures 6 and 7 ] . in this case report , in order to overcome the limitations of above - mentioned techniques a novel window technique was followed to regenerate papilla around implants during second stage surgery prior to prosthetic restoration . unlike most other procedures mentioned above , this technique avoided the labial papilla on the adjacent teeth and involved wholly the palatal papilla , which is considered to be the key element in the success of this technique .\nmoreover , there is no cross incisions on to the papilla , which may lead to , disturbed wound healing and scar formation .\nabove all avoiding more invasive surgery is considered one of the best methods of soft tissue regeneration , which is being incorporated in this technique .\nthe major advantages of this technique , when compared with earlier ones , are minimal invasive incision , less postoperative discomfort , and excellent esthetic and emergence profile obtained\n. the aim of any soft tissue procedure should be to obtain a resilient and scar less soft tissue .\nthis can be obtained with atraumatic tissue handling , minimal tension during approximation , adequate vascularity , adequate hydration , and expedient surgical procedures that do not compromise blood supply .\nthis case report shows the excellent results following the above requisites to obtain esthetic soft tissue profile .\nthe patients were followed for 2 years at regular intervals and still the esthetic results obtained during the surgery and after 2 years were the same [ figure 8 ] . with above considerations with respect to follow - up and esthetic component , this technique provided the required and desired results .\nin order to obtain esthetic papillary height and tissue integrity around implants proper and meticulous implant positioning is needed .\nbeing a long term follow - up report this technique can be considered as a simple , minimal invasive procedure , which can be followed during 2 stage surgery .", "answer": "reconstructing predictable and esthetic papilla is the most complex and challenging aspect of implant dentistry . to obtain an esthetic and predictable gingival architecture and implant restoration , \n interdental papilla plays an important role . \n the main objective of the surgeon during the second stage of implant treatment should be the creation of interdental papilla prior to prosthetic restoration . \n the aim of this case report was to demonstrate a novel window technique for developing predictable and esthetic papilla around dental implants , which was followed for 2 years with excellent esthetic results .", "id": 847} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nseptic arthritis of the shoulder is uncommon in adults . it is a surgical emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality .\na 43 years old male came to our outpatient department with complaints of pain and stiffness of his left shoulder . on examination , his shoulder movements were severely restricted .\nfurther evaluation with mri revealed septic arthritis of left gleno - humeral joint for which emergency arthroscopic debridement was done .\nseptic arthritis of shoulder may not present with classical clinical features . hence , a through clinical and radiological evaluation will help us prognosticate and treat accordingly thereby preventing complications like septic shock , osteomyelitis .\npatients with septic arthritis usually develop moderate to severe joint pain , warmth , tenderness , effusion , restricted active and passive motion , and sometimes redness .\nwe report an unusual presentation of shoulder septic arthritis in a 43 years old man with no other clinical signs and symptoms of classical septic arthritis .\na 43-year - old man presented to the orthopaedic outpatient clinic with 2 months history of pain and limited range of motion in his left shoulder .\nhis pain was insidious in onset , mild to moderate in intensity , aggravated by activities and associated with moderate rest and night pain .\npatient was diagnosed as frozen shoulder at an outside facility and had been given intraarticular depomedrol 40 mg injection for the same 40 days ago with no improvement in his symptoms .\nhe is diabetic and has liver cirrhosis and is on treatment . on physical examination ,\nthe skin colour and temperature of the left shoulder were normal , but the shoulder was tender to touch over the anterior joint line .\nmri was obtained [ fig 2 ] which showed extraosseous soft tissue enhancements around left shoulder with soft tissue abscess in inter muscular planes of supraspinatous , infraspinatous , subscapularis .\nblood test revealed normal white cell count with normal differential count , crp-13.4 mg / l ( normal<5.0 mg\nthe erythrocyte sedimentation rate was raised , at 88 mm / hour ( normal range , 0 - 20 mm / hour ) aspiration of shoulder joint was performed and fluid was sent for aerobic and anaerobic culture , afb staining , mycobacterium culture , and mycobacterium genetic testing .\narthroscopic lavage of the joint was done and articular fluid sent for repeat aerobic and anaerobic culture .\njoint visualization was markedly limited because of severe inflammation and fibrinous changes of the joint .\nthe articular cartilages of glenoid and humeral head were completely eroded down to the bone .\nsusceptibility of the isolate was determined with the disk diffusion method and it was susceptible only to colistin .\n3 ) fibrocollagenous and fibrovascular inflammed connective tissue containing proliferated blood vessels and perivascular mixed inflammatory cells and lymphoplasmacytoid cells .\nbased on preoperative and intraoperative culture report , a definitive diagnosis of polymicrobial septic arthritis of the shoulder was established and patient was treated with combination antimicrobial treatment .\nour patient had muted inflammatory response probably due to immunocompromised state ( cirrhosis and diabetes ) which is not uncommon .\nmost often it is hematogenous seeding of shoulder joint , however it can also happen after intraarticular steroid injections .\nseptic arthritis of the shoulder is more common in immunocompromised patients and intravenous drug abusers . in this case report , the patient had atypical clinical symptoms and is immunocompromised and his primary source of infection seems to be hematogenous .\nour experience with this patient highlights the importance of maintaining high index of suspicion for septic arthritis in immunocompromised patients presenting with atypical shoulder pain associated with stiffness . in the setting of suspected septic arthritis ,\nour initial pre - investigation diagnosis was atypical shoulder pain and stiffness of non specific etiology in an immunocompromised patient and infection was part of the differential diagnosis not the only diagnosis .\nesenwein et al in his report highlighted the importance of early intervention to prevent chondral damage , osteomyelitis and also to prevent systemic spread .\nvarious authors have highlighted the importance of early diagnosis and management of septic arthritis failing which could lead to osteomyelitis and septic shock . in our patient\n, the diagnosis was delayed due to atypical presentation and over reliance on clinical findings at an outside center .\nwe strongly recommend early imaging studies in immunocompromised patients presenting with shoulder pain and practitioners should avoid loosely diagnosing as shoulder pain with associated stiffness as frozen shoulders .\nklinger et al . did a retrospective study on 21 patients who underwent surgical treatment for septic arthritis of the shoulder joint between 2000 and 2007 , and he concluded that patients with symptoms for less than 2 weeks did well with arthroscopic approach and early infection can be managed arthroscopically .\nour reports show that arthroscopic washout can give good result even after 2 weeks of clinical symptoms if there is no evidence of osteomyelitis .\nseptic arthritis of the shoulder is very often due to hematogenous spread and diagnosis is often clinical .\nlaboratory investigations and imaging studies like mri and usg may be useful in establishing the diagnosis but confirmation is usually by joint aspiration .\npatients who are immunocompromised and have insidious onset of moderate to severe pain and which fails to respond to trial of conservative treatment should be subjected to either ultrasound or mri instead of x - ray because very often in these group of patients it is primarily a soft tissue pathology like impingement , rc tear , calcific tendinitis or rarely infections and malignancies .\nwe recommend that moderate pain of more than 4 weeks duration with severe stiffness in immunocompromised patient ( liver cirrhosis , renal failure , steroid treatment ) should be further evaluated with mri or ultrasound in the setting of normal x - ray and should not be loosely diagnosed as frozen shoulder .\ngoldenberg in his report emphasized the role of local as well as systemic factors that predispose patients with cirrhosis to gram - negative bacterial joint infections .\nmalnick also reported a case of spontaneous septic arthritis in a cirhottic patient that was due to e.coli .\nour study as well as other studies by goldenberg and malnick highlight the importance of including broad spectrum antibiotics with gram negative cover whilst waiting for final culture sensitivity .\nseptic arthritis of shoulder may not present with classic clinical features . a through clinical and radiological evaluation should be executed and treatment initiated promptly to prevent complications like septic shock and osteomyelitis .\nthe case highlights the importance of establishing anatomical and pathological diagnosis using mri in patients with shoulder pain instead of loosely diagnosing them as impingement or frozen shoulder .\nthe case also challenges the practice of routine shoulder depomedrol steroid injection , in the setting of secondary frozen shoulder , atleast in immunocompromised individuals .\nprimary idiopathic frozen shoulder is a rare condition and secondary frozen shoulder cases are often due to underlying shoulder pathology .", "answer": "introduction : septic arthritis of the shoulder is uncommon in adults . it is a surgical emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality . \n accurate diagnosis can be particularly challenging in patients with underlying liver disease . \n mri is a useful adjunct in early detection of atypical causes of shoulder pain.case report : a 43 years old male came to our outpatient department with complaints of pain and stiffness of his left shoulder . on examination , \n his shoulder movements were severely restricted . further evaluation with mri revealed septic arthritis of left gleno - humeral joint for which emergency arthroscopic debridement was done.conclusion:septic arthritis of shoulder may not present with classical clinical features . \n hence , a through clinical and radiological evaluation will help us prognosticate and treat accordingly thereby preventing complications like septic shock , osteomyelitis .", "id": 848} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napproximately 30% of individuals over 65 yr of age fall at least once a year ( tinetti , 2003 ) .\nfalling is a major public health and medical problem that can cause serious injuries including fracture , brain injury , and even death . as aging progresses , muscle mass , muscle strength , and joint range decrease and strides narrow as walking speed declines .\nstimulus response time and nerve conduction velocity decrease owing to changes in the nervous system , which leads to reduced balance ability .\nthis decline in physical function reduces lower extremity strength , balance , and flexibility , thereby causing frequent falling during walking ( huh et al . , 2010 ; jeoung , 2014 ; kressing et al . ,\nin korea , 21.441.6% of elderly patients receiving home care and 30.3% of elderly patients in nursing homes who have experienced falls ( gu et al . , 2006 ) , in who over 65\nyr elderly , falling were higher prevalence than other elderly disease ( kim and lee , 2006 ) . of community - dwelling elderly persons ,\n43% reported being fearful of falling , while 44% reported activity restrictions ( robertson et al . , 2002 ) .\nalmost half of older adults transitioning to frailty had a fear of falling ( kressing et al . , 2001 ) .\nfear of falling is not only the immediate result of falls but also a risk factor for falls which creates a vicious cycle between falls and fear of falling .\nvarious complex health problems arise in 50% of the elderly who have experienced falls ; 10% of them require medical treatment and 5% experience fracture .\nsince 50% of the elderly individuals who are admitted to the hospital for fall - related injuries die within 1 yr , falling is a major cause of morbidity and mortality in the elderly ( tinetti and powell . , 1993 ) . since falling induces pain , restricts activities , and disables independent living , fear of falling and the restriction of social activities due to falling greatly reduce well - being and quality of life . as such\n, falling not only leads to physical damage in the elderly but can create serious problems for social well - being ; therefore , studies on fall prevention and intervention are required .\nrecent research implicates fear of falling as a contributor to physical dependence among elderly persons ( tinetti and powell . , 1993 ) , while other studies supported the close association among exercise , physical performance , and fear of falling ( li et al . , 2005 ) .\nthe risk of falling can reportedly be reduced for those who exercise regularly , but few studies have examined its correlation with physical fitness . the purpose of this study was to examine the correlation between physical fitness and falling fears in the elderly .\na total of 173 elderly women who were 6585 yr old were recruited from a welfare center in inchon city .\nall potential participants underwent a comprehensive explanation of the proposed study , its benefits and inherent risks , and the expected time commitment .\nmedical information ( health status and medications ) was obtained from participants using a questionnaire .\nthe subjects were excluded if they were not able to walk without a cane or other assistive device or had known conditions and musculoskeletal problems limiting their safe participation in this study .\nthe physical fitness test for seniors was developed by roberta & jessie and included a 6-min walk test , grip strength , 30-sec arm curl test , 30-sec chair stand test , back scratch and chair sit and reach test , 8-foot up and go , unipedal stance , and body mass index .\nthis study approached fear of falling in two ways : ( 1 ) direct questioning focused on perceptive fear of falling ; and ( 2 ) the korean version of the fall efficacy scale - international ( kfes - i ) to measure the confidence of avoiding falling during daily activities using the level of concern about falling .\nthe kfes - i has 16 items , each of which is scored from one to four for a total score of 1664 . according to the cut point suggested by delbaere et al .\n( 2004 ) , we considered patients with a score 23 as having a higher level of concern over falling\n. statistical analysis was performed using spss for windows version 21 ( ibm spss inc . ,\na correlation analysis was conducted to examine the correlation between fall efficacy and physical fitness factors , and the correlated physical fitness factors were divided into quartiles to analyze the differences between groups . to investigate the differences in fall efficacy between physical fitness items , one - way analysis of variance ( anova ) was performed .\na total of 173 elderly women who were 6585 yr old were recruited from a welfare center in inchon city .\nall potential participants underwent a comprehensive explanation of the proposed study , its benefits and inherent risks , and the expected time commitment .\nmedical information ( health status and medications ) was obtained from participants using a questionnaire .\nthe subjects were excluded if they were not able to walk without a cane or other assistive device or had known conditions and musculoskeletal problems limiting their safe participation in this study .\nthe physical fitness test for seniors was developed by roberta & jessie and included a 6-min walk test , grip strength , 30-sec arm curl test , 30-sec chair stand test , back scratch and chair sit and reach test , 8-foot up and go , unipedal stance , and body mass index .\nthis study approached fear of falling in two ways : ( 1 ) direct questioning focused on perceptive fear of falling ; and ( 2 ) the korean version of the fall efficacy scale - international ( kfes - i ) to measure the confidence of avoiding falling during daily activities using the level of concern about falling .\nthe kfes - i has 16 items , each of which is scored from one to four for a total score of 1664 . according to the cut point suggested by delbaere et al .\n( 2004 ) , we considered patients with a score 23 as having a higher level of concern over falling .\nstatistical analysis was performed using spss for windows version 21 ( ibm spss inc . ,\na correlation analysis was conducted to examine the correlation between fall efficacy and physical fitness factors , and the correlated physical fitness factors were divided into quartiles to analyze the differences between groups . to investigate the differences in fall efficacy between physical fitness items , one - way analysis of variance ( anova )\nthere was a significant correlation between 6-min walk , 30-s chair stand test , 30-s arm curl test , chair sit and reach test , back scratch test , and 8-foot up and go test scores , unipedal stance , grip strength , and fall efficacy ( p<0.05 ) ( table 2 ) . the mean fall efficacy was 25.499.4 , higher than the fall efficacy risk score ( < 23 ) .\nanalysis of fall efficacy after the division of each physical fitness item into quartiles showed that fall efficacy was lower as physical fitness increased . moreover , the group with the highest level of physical fitness ( > 75% ) had the lowest risk of fall efficacy compared to the group with the lowest level of physical fitness ( < 25% ) .\nthe group with high physical fitness ( > 75% ) according to the 6-min walk , 30-s chair stand test , 30-s arm curl test , and 8-foot up and go test scores and grip strength had lower fall efficacy points than the cut point suggested by delbaere et al .\nrisk of falling in the elderly includes not only the result of falling itself but also the high chance of injury accompanying falls .\nanalysis of the correlation between physical performance and fear of falling in this study showed that they have a strong correlation and that fear of falling decreases as physical fitness level increases .\nstudies have reported a strong correlation between muscle strength and balance with falling ( howland et al . , 1993 ; lawrence et al . ,\nthat is , balance ability and falling are decided by how the body copes with a sudden postural disturbance in which an individual maintains a correlation between the instant reaction and the balance ability of the upper and lower body ( higuchi et al . , 2004 ; jeoung , 2014 ; walker et al , 1991 ) .\nfor this reason , muscle strength declines and the incidence of falling becomes more frequent as aging progresses .\nthe results of this study also verified that muscle strength , cardiovascular endurance , and agility are highly associated with a fear of falling as shown in previous studies .\ntherefore , a regular exercise program that can enhance muscle strength , muscle endurance , cardiovascular endurance , and agility should be emphasized .", "answer": "the fear of falling is a common psychological consequence of falling , especially for elderly individuals . \n fear of falling can lead to activity restriction and medical problems . \n the primary purpose of this study was to examine the correlation between fall efficacy and physical fitness factors in elderly women . \n we assessed physical fitness factors and investigated the korean version of the fall efficacy scale - international ( kfes - i ) in 173 participants . \n we investigated the correlation between physical fitness factors and fall efficacy . \n when the subjects were divided into four groups according to physical fitness level , subjects with high 6-m walk , 30-s chair stand test , 30-s arm curl test , chair sit and reach test , 8-foot up and go test scores and high grip strength had low fall efficacy . \n physical fitness factors were strongly associated with decreased fall fear , suggesting that physical fitness improvements play an important role in preventing or reducing the fear of falling .", "id": 849} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto demonstrate the usefulness of enhanced depth imaging optical coherence tomography ( edi - oct ) in investigating choroidal lesions inaccessible to ultrasound sonography .\nin a 60-year - old woman with an asymptomatic choroidal nevus , normal oct was used to observe the macula and edi - oct to image the choroidal nevus that was inaccessible to ultrasound .\nthe exact location of the lesion in the choroid and the dimensions of the nevus were measured .\nthe lesion was located in the superior macula , and the nevus was homogeneous in its reflectivity .\nwe observed a thickened choroid delineated by the shadow cone behind it , measuring 1,376 325 m in the larger vertical cut and 1,220 325 m in the larger horizontal cut in an image with a 1:1 pixel mapping and automatic zoom .\nedi - oct appears to be an excellent technique for measuring choroidal nevi and all choroidal lesions accessible to oct imaging by depicting their exact location in the choroid , their dimensions , and their demarcation from the surrounding healthy tissue , thus allowing for a more efficient and accurate follow - up .\nchoroidal nevus is the most common tumor of the ocular fundus , present in 7% of the white population [ 1 , 2 ] . despite its benign nature\n, it presents a risk of visual loss and visual field loss , and can rarely transform into malignant melanoma .\noptical coherence tomography ( oct ) and ultrasonography have been used for imaging choroidal nevi . recently\n, enhanced depth imaging oct ( edi - oct ) has been used in order to measure choroidal thickness in normal and pathologic eyes [ 3 , 4 ] . here\n, we report a case of a flat choroidal nevus inaccessible to ultrasound sonography that was evaluated by edi - oct .\na 60-year - old woman was referred to our department with an asymptomatic choroidal nevus in her left eye . her best - corrected visual acuity was 20/20 in both eyes . slit lamp and fundus examinations of the right eye were normal . in the left eye , the anterior segment was normal ; however , on fundoscopy a choroidal nevus located in the superior macula was observed ( fig .\nspectral - domain ( sd ) oct ( heidelberg engineering , heidelberg , germany ) revealed normal foveal thickness ( fig .\n2 ) . the flat nevus was inaccessible to ultrasound sonography , and edi - oct was used to image its posterior surface ( fig .\nedi - oct is a new technique that consists of positioning a heidelberg sd - oct close enough to the eye in order to obtain an inverted image , averaged for 100 scans .\nthe advantage of this technique is that the sensitivity of the imaging in deeper tissue layers is increased , and thus the obtained measurements are more accurate .\nwe employed this technique to image the location of the nevus in the choroid and obtain its dimensions as a reference measure for the follow - up examination ( fig .\n3 ) . heidelberg sd - oct provides an exact correlation between the oct image and the infrared photograph . as infrared light\nis absorbed by melanin , the nevus appears brighter . in the edi - oct image\n, the lesion appears homogeneous and hyperreflective at the level of the large choroidal vessels , masking the underlying choroidal vasculature .\nthe choroidal thickness at the level of the nevus appears greater than the neighbor choroid ( fig .\nthe diameter of the nevus was calculated based on the presence of a shadow cone created by the lesion 's lateral borders .\nthe choroidal thickness was measured based on the hyperreflectivity between the bruch 's membrane and the beginning of the shadow cone ( fig .\nthe choroid measured 1,220 325 m in the larger horizontal cut and 1,376 325 m in the larger vertical cut in an image with a 1:1 pixel mapping and automatic zoom ( fig .\nedi - oct appears to be an excellent technique for evaluating flat choroidal nevi that are inaccessible to ultrasound sonography and accessible to oct imaging , displaying simultaneously the lesion and the retinal changes .\nit is a reproducible examination that allows depiction of the exact location of the nevi in the choroid , their dimensions and their demarcation from the surrounding healthy tissue . to date , the software available for sd - oct does not allow for objective measures .\nthe subjective measures obtained are useful upon comparison with the follow - up images . in order to limit the possibility of bias\n, these follow - up images must be obtained and compared with the same sd - oct machine .\nwe believe that this technique is clinically useful and , together with color fundus photography , can provide a more efficient and accurate follow - up of choroidal nevi .", "answer": "purposeto demonstrate the usefulness of enhanced depth imaging optical coherence tomography ( edi - oct ) in investigating choroidal lesions inaccessible to ultrasound sonography.methodsin a 60-year - old woman with an asymptomatic choroidal nevus , normal oct was used to observe the macula and edi - oct to image the choroidal nevus that was inaccessible to ultrasound . \n the exact location of the lesion in the choroid and the dimensions of the nevus were measured.resultsthe lesion was located in the superior macula , and the nevus was homogeneous in its reflectivity . \n we observed a thickened choroid delineated by the shadow cone behind it , measuring 1,376 325 m in the larger vertical cut and 1,220 325 m in the larger horizontal cut in an image with a 1:1 pixel mapping and automatic zoom . \n the macular profile and thickness were both normal.conclusionsedi-oct appears to be an excellent technique for measuring choroidal nevi and all choroidal lesions accessible to oct imaging by depicting their exact location in the choroid , their dimensions , and their demarcation from the surrounding healthy tissue , thus allowing for a more efficient and accurate follow - up .", "id": 850} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nanthrax , a zoonotic disease caused by bacillus anthracis ( b. anthracis ) , primarily affects herbivores including sheep , cattle , horses , and other domestic animals.1 humans may be affected as a result of exposure to an infected animal or animal products .\nthis organism has received recent attention as a potential agent of bioterrorism.1 three forms are described : cutaneous , inhalational , and gastrointestinal.1 we describe a patient with oculocutaneous anthrax .\na 39-year - old male presented to our outpatient clinic with a 4-day history of fever and swelling of the left upper and lower eyelids associated with pain , watering , and difficulty in opening the eyelids .\nthe patient reported that he was prescribed tablets and injections by a general practitioner , but was unable to provide details of this treatment to us . on examination\n, there was brawny nonpitting edema of the upper and lower eyelids of the left eye and left side of the face ( figure 1 ) .\nthere was an ulceration and black discoloration along the left lower lid margin with serosanguinous discharge .\nserous fluid from the eyelid and blood were collected and sent for conventional cultural methods and polymerase chain reaction ( pcr ) test .\na 39-year - old male presented to our outpatient clinic with a 4-day history of fever and swelling of the left upper and lower eyelids associated with pain , watering , and difficulty in opening the eyelids .\nthe patient reported that he was prescribed tablets and injections by a general practitioner , but was unable to provide details of this treatment to us . on examination\n, there was brawny nonpitting edema of the upper and lower eyelids of the left eye and left side of the face ( figure 1 ) .\nthere was an ulceration and black discoloration along the left lower lid margin with serosanguinous discharge .\nserous fluid from the eyelid and blood were collected and sent for conventional cultural methods and polymerase chain reaction ( pcr ) test .\nthe patient s dna was extracted using the qia amp dna blood mini kit ( qiagen , hilden , germany ) according to the manufacturer s instruction . a 596-bp fragment of the protective antigen ( pa ) gene , pa ( f)-tcc taa cac taa cga agt cg and pa ( r)-gag gta gaa gga tat acg gt and a 846-bp fragment of the capsule ( cap ) gene , cap ( f)-ctg agc cat taa tcg ata tg and cap ( r)2,3 of b. anthracis were used as the target for anthrax pcr .\nthe dna was amplified in a total volume of 50 l with the above mentioned primers , 200 m ( each ) deoxynucleotide triphosphates , 1x pcr buffer , 1.5 mm mgcl2 and 2.5 units of taq polymerase ( amplitaq gold - applied biosystems , california , usa ) and followed by the addition of 5 l of the template dna .\nthermal cycling was performed at 94c for 5 minutes ( initial denaturation ) followed by 35 cycles at 94c for 1 minute , 52c for 1 minute ( annealing ) , 72c for 2 minutes ( extension ) and the final extension at 72c for 5 minutes ; cooled to 4c.4 thermal cycling was done in the gene amp pcr system 9200 ( applied biosystems , california , usa ) .\na 15 l portion of the pcr product and 5 l of 10% tracking dye ( 0.02% xylene cyanol , 0.02% bromophenol blue and 50% glycerol ) was added to the pcr tube .\nfifteen microliters of this mix were loaded into the wells in the agarose ( amersham pharmacia , new jersey , usa ) .\nthe pcr products were analyzed by submarine gel electrophoresis through a 1% agarose gel in 1x tae buffer .\nthe gel was run at 120 volts for 60 minutes , stained with 0.5 g / ml of ethidium bromide ( amersham pharmacia , new jersey , usa ) , visualized and recorded under uv4 in the gel doc 2000 system ( bio - rad , california , usa ) .\nthe gene ruler 100-bp ( 3000100bp ) dna ladder plus ( mbi fermentas , usa ) was used as the molecular standard .\nthe pcr from the fluid and the blood were positive for the gene encoding the protective antigen ( pa gene ) and the capsule ( cap gene ) of b. anthracis ( figure 2 ) .\nthe patient was started on injection crystalline penicillin , 2 million international units ( 1250 mg ) every 2 hours intravenously .\nno topical therapy was prescribed , however , the patient was given anti - inflammatory agents ( ibuprofen ) .\non completion of a 10-day course of intravenous antibiotics , he was discharged on oral penicillin g 500 mg every 6 hours .\nalthough the eschar reduced in size over time , it was firmly adhered to the underlying tissue . when the eschar was removed after 1 month of the onset of illness , an ulcerated undersurface was observed ( figure 4 ) .\nthe ulceration healed over the next 2 weeks with scarring and ectropion of the left lower lid ( figure 5 ) . the low grade lid edema and mechanical ptosis of the left upper eyelid resolved over the next few weeks .\nb. anthracis is commonly found in agricultural environments . it is a gram - positive , aerobic , endospore - forming bacilli that , in the vegetative form , has a poor survival rate outside an animal or human host.5 it is capable of producing fatal infection in livestock and in humans.1 anthrax\nis considered to be one of most dangerous biological weapons.6 humans are infected when spores are introduced into the body by contact with infected animals or animal products.1 cutaneous anthrax has been reported to occur as preseptal cellulitis in the eyelids.7,8 cutaneous anthrax , if untreated , leads to life - threatening septicemia.1 this report highlights that a high index of clinical suspicion and prompt institution of appropriate therapy are essential for a successful outcome . since lesions can become sterile within 24 hours of antimicrobial therapy , confirmation of diagnosis can be made using pcr,24,9 as was done in our patient , when the conventional cultural methods fail to identify the etiology or when patients have already received antimicrobial therapy .", "answer": "anthrax , a zoonotic disease that primarily affects herbivores , has received recent attention as a potential agent of bioterrorism . \n we report a patient who presented with a 4-day history of pain , watering and difficulty in opening the left upper and lower eyelids , and fever . \n clinical examination revealed brawny nonpitting edema with serosanguinous discharge . \n the history of the death of his sheep 1 week prior to the illness provided the clue to the diagnosis . although standard cultures of the blood and the serous fluid from the lesion were negative , probably as a result of prior treatment , \n the diagnosis of cutaneous anthrax was made by a polymerase chain reaction ( pcr ) test of the serous fluid . \n serial photographs demonstrating resolution of the lesion with appropriate antibiotic therapy are presented .", "id": 851} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrecently , new oral anticoagulants have been approved as alternatives to warfarin for patients with atrial fibrillation .\nrivaroxaban is one of the novel anticoagulants , which is an oxazolidinone derivative and inhibits both free factor xa and factor xa bound with the prothrombinase complex .\nit is a highly selective direct factor xa inhibitor with oral bioavailability and rapid onset of action .\nthere are some advantages of the new agents compared with warfarin including rapid anticoagulation after an oral dose and lack of dietary or drug - drug interaction . however , there are no specific antidotes for the anticoagulant effect of rivaroxaban in the event of a major bleeding , unlike warfarin\n. we present a case of spontaneous rectus sheath hematoma ( rsh ) during rivaroxaban therapy for atrial fibrillation in an elderly female patient .\na 75-year - old woman presented to the emergency department with the complaints of fatigue and abdominal pain after coughing .\nthe patient had been started on new oral anticoagulant agent rivaroxaban therapy for nonvalvular atrial fibrillation for 3 days .\nthe dose of 20 mg / day rivaroxaban was started because the creatinin clearance of the patient was above 50 ml / min .\nshe had a blood pressure of 70/40 mmhg and an irregular heart rate of 115 beats / min on admission .\nthe patient had no history of any trauma or surgery ; she reported that the symptoms started after vigorous coughing .\nblood analyses revealed leukocytosis ( 26.5 k / ul ) accompanied by severe anemia ( 5.4 g / dl ) .\nplatelet counts were within normal ranges and her international normalized ratio ( inr ) was 1.48 .\nher abdominal x - ray was normal and the stool occult blood test was negative .\nafter the first treatment , the patient was transferred to the intensive care unit ( icu ) .\nrepeated abdominal examination in the icu revealed increased tenderness and a palpable mass on the left side of the umbilicus .\nnoncontrast abdominal computerized tomography scan showed a left - sided rsh , 102 45 mm in size [ figure 1 ] . a specific antidote for rivaroxaban\nis not available then the patient was treated with fluid resuscitation and packed red blood cells .\ncomputed tomography scan of the abdomen shows a left - sided rectus sheath hematoma ( arrow )\nrivaroxaban is an oral anticoagulant agent that directly inhibits factor xa and interrupts both the intrinsic and extrinsic pathway of the coagulation cascade .\nrivaroxaban is currently indicated for use in patients for atrial fibrillation and prophylaxis of deep venous thrombosis .\nit does not require inr monitoring like warfarin . with the increasing use of the new anticoagulant agents like rivaroxaban in atrial fibrillation , bleeding complications due to these agents\nthere are no specific antidotes for the anticoagulant effect of rivaroxaban and other new oral anticogulants unlike warfarin , thus the management of the bleeding complications include support and observation .\ncurrently , no available specific antidote exists for the management of rivaroxaban - associated bleeding events , but supporting therapy is useful which are likely to be effective for the majority of patients because of the short half - lives of these agents .\nrecent studies showed that rivaroxaban was noninferior to warfarin for the primary endpoint of stroke and systemic embolism .\nthere was no reduction in rates of mortality or ischemic stroke , but a significant reduction in hemorrhagic stroke and intracranial hemorrhage .\nthe primary safety endpoint was the composite of major and clinically relevant nonmajor bleeding , which was not significantly different between rivaroxaban and warfarin but , with rivaroxaban , there was a significant reduction in fatal bleeding , as well as an increase in gastrointestinal bleeds and bleeds requiring transfusion .\nthe main causes of the rsh include anticoagulant therapy , hematological disorders , trauma , excessive physical exercise , coughing , sneezing , and pregnancy . especially in elderly patients the risk of rsh may be increased due to the impaired functional status and weakened rectus muscle\n. early recognition , rapid assessment and treatment are important to reduce the complications such as hemodynamic instability , abdominal compartment syndrome , multiorgan dysfunction and even death .\nthe treatment of such a hematoma includes transfusion with packed red blood cells and supporting therapy based on regularly monitoring of hemoglobin levels .\nrivaroxaban has a mean terminal half - life of 7 - 11 h so in bleeding events supporting therapies are likely to be effective for the majority of patients .\nseveral studies have shown that prothrombin complex concentrate may be useful in reversing the effects of rivaroxaban .\nother possible measures include the use of recombinant factor viia to reduce bleeding or the use of activated charcoal to reduce absorption in cases of overdose .\nseveral factors are reported which increase the risk of patients developing hemorrhage while receiving rivaroxaban , these include advanced age , hypertension , history of hepatic / renal disease , previous stroke , coagulopathy , concomitant use of antiplatelet agents and alcohol consumption .\njaeger et al . have reported a 61-year - old female patient who developed a spontaneous spinal epidural hematoma after being treated by rivaroxaban .\nboland et al . also reported acute onset severe gastrointestinal tract hemorrhage in a postoperative patient taking rivaroxaban after total hip arthroplasty . in our patient\n, there was no other medication except rivaroxaban that could cause the hematoma . based on naranjo 's scale\n, a score of 7 showed that the rivaroxaban was the probable cause of the rsh .\nseveral case reports of muscle hematoma due to the antiplatelet and anticoagulant agents have been reported previously , but this is the first reported case of spontaneous rsh due to the rivaroxaban .", "answer": "rivaroxaban is an oral anticoagulant agent that directly inhibits factor xa and interrupts both the intrinsic and extrinsic pathway of the coagulation cascade and is currently indicated for use in patients for atrial fibrillation and prophylaxis of deep venous thrombosis . \n the present case reports of spontaneous rectus sheath hematoma during rivaroxaban therapy for atrial fibrillation in a 75-year - old woman .", "id": 852} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nEnantioselective Synthesis of Pyrroloindolines by a Formal [3+2] Cycloaddition Reaction\n\nPaper sections:\n\nPyrroloindoline alkaloids are an important class of natural products1 that exhibit an impressive array of promising biological properties, including anticholinesterase,2 antiinflammatory,3 and anticancer activities.4 Owing to their medicinal relevance and structural complexity, pyrroloindoline alkaloids have served as a fertile area for the discovery and development of new chemical reactions.5,6 As part of a program targeting new methods for the total synthesis of alkaloid natural products, we sought to develop a convergent method to prepare enantioenriched pyrroloindolines.
From a design perspective, it was hypothesized that pyrroloindolines (5) could be assembled through the union of a C(3)-substituted indole (1) and a 2-amidoacrylate (2) in what would constitute a formal [3+2] cycloaddition reaction (Scheme 1). It was envisioned that the reaction would proceed through a stepwise mechanism in which a Lewis acid activates 2-amidoacrylate 2, promoting conjugate addition by the indole to give iminium ion 4. Subsequent intramolecular attack of the nucleophilic amide would provide pyrroloindoline 5.
The proposed reaction would harness the intrinsic C(3)-nucleophilicity of the indole substrate and, in principle, could provide rapid access to a variety of pyrroloindolines from simple C(3)-substituted indole precursors.7,8 Although 2-amidoacrylates are typically poor electrophiles for conjugate addition reactions due to the electron donating effects of the nitrogen lone pair, Piersanti and coworkers recently reported that EtAlCl2 promotes the reaction of indole (1, R=R1=R2=H) and methyl 2-acetamidoacrylate to provide the C(3)-Friedel-Crafts type product 3 (R=R2=H, R3=R4=Me, Scheme 1).9
Preliminary experiments were conducted in which equimolar mixtures of commercially available methyl 2-acetamidoacrylate (8) and 1,3-dimethylindole (6) were exposed to various Lewis acids. We were pleased to find that strong Lewis acids such as EtAlCl2, TiCl4, and SnCl4 provided isolable quantities of the desired pyrroloindoline 7a, as well as varying amounts of the C(2)-Friedel-Crafts type product analogous to 3 (not shown). After a preliminary survey of reaction parameters, the use of SnCl4 (1.2 equivalents) in dichloroethane at room temperature was found to provide pyrroloindoline 7a in 64% yield as a 6:1 mixture of exo and endo diastereomers (Table 1, entry 1; exo diastereomer is shown).
At this stage we wished to determine the feasibility of accessing enantioenriched pyrroloindolines using this formal [3+2] cycloaddition reaction. To this end, a screen of chiral diol additives anticipated to form chiral Lewis or Br\u00f8nsted acid complexes with SnCl4 was conducted.10 Of the conditions evaluated, it was found that utilization of a 1.1:1 mixture of (R)-BINOL and SnCl4 provided pyrroloindoline 7a in 86% yield as a 4:1 diastereomeric mixture favoring exo-7a, which was formed in 64% ee (Table 1, entry 2).11,12 Interestingly, the minor, endo diastereomer was formed in 83% ee. In follow-up studies, a side-by-side comparison of two reactions varying only by the presence or absence of (R)-BINOL showed that it accelerates the rate of 7a formation and increases the overall conversion.13
Based on these observations, it was hypothesized that catalytic quantities of (R)-BINOL may still provide pyrroloindoline 7a with good levels of enantioselectivity. Indeed, use of as low as 10 mol % (R)-BINOL furnished 7a without significantly affecting the observed enantioselectivity (Table 1, entries 3\u20135). Whereas 10 mol % (R)-BINOL provided comparable selectivities for the formation of 7a, 20 mol % (R)-BINOL imparted consistently higher enantioselectivities for more functionalized substrates (vide infra), and was therefore utilized in subsequent experiments. Control experiments confirmed that no reaction occurred in the absence of SnCl4, and that 1.2 equivalents SnCl4 were required to drive the reaction to high conversions.14
In an effort to improve the enantioselectivity of the reaction, the amide and ester groups of the acrylate were modified.15,16 An increase in ee was observed when methyl 2-trifluoroacetamidoacrylate (9) was employed (Table 1, entry 7). A similar increase was observed using benzyl 2-acetamidoacrylate (10, entry 8). Gratifyingly, these effects proved to be additive: use of benzyl 2-trifluoroacetamidoacrylate (11) provided pyrroloindoline 7d in 81% yield and 91% ee. Preliminary studies indicated that chlorinated solvents provided the best combination of yields and selectivities. A further screen identified methylene chloride as the solvent of choice. Under our optimized conditions, pyrroloindoline 7d was isolated in 86% yield as a 4:1 mixture of exo and endo diastereomers, which are formed in 94% and 91% ee, respectively (entry 10).17
Having identified conditions to prepare 7d in high yields and enantioselectivities, a survey of indole substrates was conducted. Substrates substituted at C(5) with electron-donating and electron-withdrawing substituents provided uniformly high ee's, although a moderate decrease in yield was observed with electron poor substrates (Scheme 2, 13a\u2013d). 1,3,6-Trimethylindole reacts smoothly to give a 4:1 mixture of exo- and endo-13e in 91% yield (94% and 90% ee, respectively).
More functionalized substituents are also tolerated at C(3) of the indole substrate. Pyrroloindolines bearing t-butyldimethylsiloxyethyl (13f) and phenylethyl (13h) substituents are prepared in moderate to good yield and high enantioselectivity (Scheme 2). Most notably, use of N-methyl-1,2,3,4-tetrahydrocarbazole provided a single diastereomer of pyrroloindoline 13g in 65% yield and 86% ee. Using this reaction, the aza-propellane core of natural products such as vincorine18 and minfiensine19 was prepared in only two steps from commercially available 1,2,3,4-tetrahydrocarbazole.
Whereas the exo diastereomer predominates in the (R)-BINOL\u2022SnCl4-catalyzed formation of the pyrroloindolines shown in Scheme 2, it is known that the endo diastereomer of similar compounds is favored thermodynamically.20,21 Accordingly, treatment of a 4:1 mixture of exo-7d and endo-7d diastereomers (94% and 91% ee, respectively) with excess DBU in CD2Cl2 resulted in epimerization to give a greater than 10:1 endo:exo mixture of products after 72 h (Scheme 3). Interestingly, the endo-7d product was recovered in 56% ee, favoring the opposite enantiomer.22 In a subsequent experiment, exposure of diastereomerically pure exo-7d to DBU (10 equiv) provided ent-endo-7d in 94% ee. Exposure of diastereomerically pure endo-7d to the epimerization conditions returned endo-7d without significant erosion of enantiomeric excess. Taken together, these studies suggest that the initially formed exo and endo diastereomers of 7d must be of opposite enantiomeric series. From a synthetic perspective, the diastereomers can be separated prior to subsequent functionalization to avoid erosion of optical activity through this epimerization mechanism.
At this time the mechanism of the reaction remains to be elucidated. As exo- and endo-7d have opposite configurations at C(3), analysis of the diastereomeric and enantiomeric ratios suggests that the first step of the reaction (conjugate addition) occurs with modest levels of catalyst control, whereas the enolate protonation step occurs with high levels of catalyst control.23 In effect, the catalyst-controlled protonation step serves to resolve the mixture of enantiomeric intermediates. Yamamoto and coworkers have demonstrated that BINOL\u2022SnCl4 behaves as a Lewis acid-assisted Br\u00f8nsted acid that promotes a number of enantioselective protonation reactions.11a\u2013c It is unusual, however, for high enantioselectivities to be observed when employing an excess of SnCl4 relative to BINOL. The observation that at least 1 equivalent SnCl4 is required for high conversions, coupled with the fact that use of strong Br\u00f8nsted acids24 in the absence of SnCl4 fail to provide 7d, may suggest that this reaction benefits from cooperative Lewis acid-Br\u00f8nsted acid activation.
In conclusion, a convergent method to prepare enantioenriched pyrroloindolines is described. The optimal conditions employ (R)-BINOL as a catalyst in the presence of stoichiometric SnCl4, and provide access to functionalized pyrroloindolines in uniformly high ee's. The application of this methodology to the total synthesis of pyrroloindoline natural products, as well as studies aimed at understanding the mechanism of this new transformation are the focus of ongoing research in our laboratory.25
", "answer": "(R)-BINOL\\xe2\\x80\\xa2SnCl4 was found to catalyze a formal [3+2] cycloaddition reaction between C(3)-substituted indoles and 2-amidoacrylates to provide pyrroloindolines. A variety of pyrroloindolines were prepared with high enantioselectivity in one step from simple precursors. This methodology is expected to facilitate the total synthesis of pyrroloindoline alkaloids, an important class of biologically active natural products.", "id": 853} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsplit - liver transplantation ( slt ) is an attractive alternative procedure to expand the donor pool in patients waiting for liver transplantation .\nthe standard split - liver procedure for a child and an adult ( adult / pediatric split liver ttransplantation , a / p slt ) , by splitting segment ii - iii for pediatric recipient and segment i - iv - v - vi - vii - viii for an adult , is an accepted surgical option with good results both for the adult and for pediatric recipient .\nbiliary complications continue to be the major cause of morbidity after slt with a reported high incidence ranging between 10% and 32% [ 1 , 2 ] . as a consequence of bile duct anatomic variations\n, slt requires a precise knowledge of the liver anatomy [ 3 , 4 ] .\nthe challenge of this procedure is represented by a preoperative radiological assessment of the biliary anatomy often unavailable at the donor 's hospital .\nthus the risk of biliary duct injury during the splitting procedure is usually considered higher than during living donor procedure . in this report\nwe describe an uncommon late biliary complication that occurred after slt and was successfully treated by a multidisciplinary approach . \na 63-year - old male with hepatitis c - related cirrhosis was referred for liver transplantation to our institution .\nwe performed a conventional a / p slt with in situ technique providing the left lateral segment for a child ( segments ii - iii ) and leaving the right lobe graft ( segment i - iv - v - vi - vii - viii ) for an adult recipient .\nthe celiac trunk was left on the left graft while the right hepatic artery remained on the right graft .\nthe patient was transplanted using the piggy - back technique without a veno - venous bypass .\nthe biliary tract was reconstructed performing a duct - to - duct anastomosis using a t - tube by our standard technique previously described .\na cholangiography through the t - tube was performed on postoperative day 14 , and the t - tube was clamped before patient discharge .\nthree months after a / pslt the t - tube was removed after a cholangiography with normal findings .\none year after transplant the patient showed abnormal liver function tests , hyperbilirubinemia , leukocytosis , and elevated g - glutamyl transpeptidase ( ggt ) , and mild elevation in alanine transaminase ( alt ) . \nthe patient underwent a doppler ultrasound that showed ( a patent hepatic artery ) an intrahepatic bile duct dilatation and an anastomotic biliary stricture .\nthe anastomotic stricture was treated by stenting the main biliary duct during an endoscopic retrograde cholangiopancreatoghaphy ( ercp ) without any evidence of intrahepatic biliary dilatation .\nafter this procedure the patient was submitted to a percutaneous transhepatic cholangiography ( ptc ) showing a complete obstruction of segments vi and vii biliary branches near the duct - to - duct biliary anastomosis ( figure 1 ) . \nthe patient was discharged leaving the external biliary drain open allowing bile drainage and an easy access for repeated radiologic treatment and an internal stent in the common bile duct .\nthree months later the patient underwent a surgical revision because of repeated episodes of cholangitis . during surgery\nan intraoperative cholangiography was performed through the biliary drain confirming a bile duct dilatation at the level of segments vi and vii . \nit was impossible to cross the biliary stricture by a torque catheter and by hydrophilic guide wire ( figure 2 ) .\nwe supposed that the segmentary bile duct branch of posterior segments vi and vii draining in the left bile duct was unidentified and tied at the time of the in situ split - liver procedure during the parenchymal transection .\na primary biliary reconstruction by biliary repair or biliodigestive anastomosis was considered at high risk because of the presence of postsurgical adhesions sand due to fibrotic tissue replacing the parenchymal transected area . a liver resection of the dilated segments vi and vii was considered at high risk of leaving an inadequate liver mass . \nwe decided to perform a permanent intraoperative obliteration of the dilated intrahepatic ducts by a percutaneous embolization using a nonresorbable agent . with a fluoroscopic guidance through the transhepatic access we positioned a 5-french polyethylene catheter inside the ducts , preliminary flushed by a nonionic dextrose solution .\nwe then injected the tissue adhesive agent n - butyl cyanoacrylate ( nbca , glubran 2 , gem , viareggio , italy ) mixed with ionized oil ( lipiodol , guebert , aulnay - sous - bois , france ) for opacization in a ratio of 1:5 .\nthis solution completely filled the biliary duct , and the occlusion was totally accomplished in a few seconds ( figure 3 ) . during the first 3 days after the chemical bile duct embolization , the patient had a low fever with a slightly abnormal liver function test .\na computed tomography ( ct ) scan performed 6 months later showed no sign of hepatic abscesses , and the bile duct dilatation was completely occupied by the nbca - lipiodol mixture .\none year after the procedure patient showed normal liver function tests without no episodes of cholangitis .\nchemical bile duct embolization treatment could represent a valuable solution to treat uncommon biliary complications .\nthese tissue adhesive glues are low - viscosity liquid monomers that undergo rapid polymerization and solidification when they come into contact with organic fluids such as bile .\nnbca is a permanent liquid embolic material that produces long - term occlusion in vessels of various size through an inflammatory tissue response resulting in vessel thrombosis or tissue atrophy .\nlittle is known about the use of cyanoacrylate compounds , and unlike european countries the use of glubran has not been approved by the food and drug administration yet . \nother authors have described the efficacy of biliary duct ablation by nbca in patients with persistent postsurgical bile leaks after lobectomy or cholecystectomy .\nvu et al . treated six patients with persistent postsurgical bile leaks as a complication after hepatic lobectomy or cholecistectomy using nbca glue for the obliteration of isolated segmental bile ducts in four cases .\nendoscopic treatment of biliary leakage by nbca has been described by seewald in nine patients in whom primary stent placement or nasobiliary drain was unsuccessful .\ndescribed the use of a cyanoacrlylate in the treatment of a pancreatic fistula after distal pancreatectomy .\nthe percutaneous interventional technique represents an effective valuable approach to reduce mortality and morbidity in the treatment of biliary complications after liver transplantation .\nthe use of nbca in obliteration of a dilated bile duct seems to be a safe procedure with good results providing a less invasive option than hepatic resection above all in high - risk patients with posttransplant bile duct injuries , decreasing the morbidity associated with chronic external biliary drainage .\nfuther studies are needed to determine whether this approach is effective and safe and whether it could reduce hospital stay and costs .", "answer": "biliary complications continue to be a major cause of morbidity after split - liver transplantation ( slt ) . in this report \n we describe an uncommon late biliary complication . \n one year after slt the patient showed an intrahepatic bile dicy dilatation with severe cholangitis episodes . \n the segmentary bile duct of hepatic segment vi - vii draining in the left duct was unidentified and tied at the time of the in situ split - liver procedure . \n we perform a permanent obliteration of the dilated intrahepatic ducts by a percutaneous embolization using an n - butyl cyanoacrylate ( nabc ) . the management of biliary complications after slt requires a multidisciplinary approach . \n the use of nbca in obliteration of a dilated bile duct seems to be a safe procedure with good results providing a less invasive option than hepatic resection and decreasing the morbidity associated with chronic external biliary drainage . \n further studies are needed to determine whether this approach is effective and safe and whether it could reduce hospital stay and cost .", "id": 854} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen a body part is under pressure , tissue cells do not \n receive nutrients properly , thereby resulting in their death and the appearance of a lesion . \n\nin addition to exposure to pressure , an elevated body temperature and a high skin humidity \n may also contribute to pressure ulcer formation , which appears as an irritation in the upper \n layers of the skin and may reach muscles and bone tissue2 .\npressure ulcers are harmful to subjects , particularly those who \n have additional risk factors related to poor health3 . in this sense ,\ntherefore , it is important to prevent pressure \n ulcers . the correlation between being seated and\nthe presence of pressure ulcers has been reported \n frequently since epidemiological studies of pressure ulcers were first conducted4 .\nbarbenelet et al . reported the pressure \n ulcer prevalence survey in the united kingdom and noted that chair - bound patients \n consistently exhibited a higher frequency of developing pressure sores compared with \n bed - bound patients with a similar degree of helplessness5 .\nother surveys have also shown this association between being seated \n and the presence of pressure ulcers6 , 7 .\nthe guidelines concerning pressure ulcers issued by the national institute for health and \n care excellence ( nice ) in the united kingdom include a statement regarding seating , in which \n the authors stressed the need for qualified assessment of seating needs , the importance of \n correct eating positions , and the need to maintain posture and support the feet when using a \n wheelchair8 . in people who are at risk \n for pressure ulcers or in those with bedsores , pressure redistribution must be tended to \n such that no pressure is applied to the pressure ulcer9\n. a number of management strategies , including a number of \n commercially available alternating pressure cushions and wedges , can provide pressure \n redistribution10 , 11 .\nlee reported the effectiveness of cushions and an anterior wedge sitting position in \n pressure ulcers . in their study\n, they showed that the type of cushion and appropriate height \n wedges made a statistically significant difference in sitting pressure12 .\nseveral studies found a correlation between cushion types \n and sitting pressure or between anterior wedge height and sitting pressure .\nhowever , \n pressure redistribution when cushions and wedges are applied simultaneously has not been \n investigated .\nconsequently , the purpose of this study was to analyze user cushion interface pressure \n redistribution when different cushion types and height anterior wedges are applied \n simultaneously for healthy volunteers .\nthis \n study was a pilot study to direct future research , to perform adult norm pressure \n mapping .\nall participants were identified as able - bodied subjects , and the \n procedure was fully explained to them .\nthe exclusion criteria included any type of sitting problems , or \n hearing , visual , or cognitive impairments that interfere with accurate participant \n assessments .\nthe subjects were informed that they could withdraw from the study at any \n stage for whatever reason .\nparticipant characteristics are provided in table 1table 1.general characteristics of the subjectsmale ( n=15)female ( n=21)age ( years)21.7 2.020.1 0.5weight ( kg)66.1 8.753.9 9.2height ( cm)171.8 6.2158.4 5.1seat to footplate ( cm)46.7 5.343.8 4.6seat depth ( cm)49.5 3.545.9 4.9seat width ( cm)36.0 3.434.3 3.6hip ( )99.9 5.599.5 7.2knee ( )93.9 5.999.5 6.8ankle ( )93.4 5.797.3 6.3 .\nthe conformat system and research software v.7.2 were used for pressure mapping and data \n acquisition , respectively .\none occupational therapist and three university students \n collected the pressure data while the participants were sitting on a firm surface without a \n cushion , a 5-cm height gel cushion , a 5-cm height memory foam cushion , a 3-cm anterior wedge \n without cushion , a 3-cm anterior wedge with a 5-cm height gel cushion , a 3-cm anterior wedge \n with a 5-cm height memory foam cushion , a 6-cm anterior wedge without cushion , a 6-cm \n anterior wedge with a 5-cm height gel cushion , and a 6-cm anterior wedge with a 5-cm height \n memory foam cushion .\nthe participants were instructed to keep their chins tucked in , spines \n straight , hands on their thighs , and pelvis neutrally positioned when sitting on the \n cushions .\nthey were initially instructed to flex their hips , knees , and ankles at \n approximately 90 and to put their feet flat on the floor . each joint angle and sitting \n position were checked for each measurement .\nafter measurement , the pressure map was divided into four quadrants on screen graphics , with \n each quadrant representing the left hip , left thigh , right hip , and right thigh . for the \n quadrant division ,\nthe mergl method was adapted and used to analyze the sitting pressure on \n the cushion .\nthe peak pressure \n was the mean of the maximum pressures measured with four sensors in each quadrant .\nthe mean \n pressure was the mean of the pressures measured with every sensors in each quadrant .\nthe participant characteristics were \n tested by descriptive statistical analysis , and results were tested by a one - way analysis of \n variance and post - hoc analysis .\ngeneral demographic information , including age , weight , height , and sitting position , is \n shown in table 1 . in both genders ,\nthe mean and \n peak pressures were the lowest when sitting on a 5-cm foam cushion .\nthe mean pressure in the \n hip and thigh was the highest on a 6-cm wedge and on a firm surface , respectively .\nthe mean \n pressure was observed to increase in the following order : a foam cushion , a 3-cm anterior \n wedge with a 5-cm foam cushion , a 6-cm anterior wedge with a 5-cm foam cushion , a 5-cm gel \n cushion , a 3-cm anterior wedge with a 5-cm gel cushion , a 6-cm anterior wedge with a 5-cm \n gel cushion , a 3-cm anterior wedge without cushion , without cushion , and a 6-cm anterior \n wedge without cushion ( tables 2table 2.peak pressure distribution according to wedge height and cushion type ( n=36 , \n mmhg)firm surface5 cm gel cushion5 cm foam cushion3 cm wedge5 cm gel cushion with 3 cm wedge5 cm foam cushion with 3 cm wedge6 cm wedge5 cm gel cushion with 6 cm wedge5 cm foam cushion with 6 cm wedgerhpp*304.43 95.46123.04 71.21116.09 69.57308.64 91.46131.88 55.87122.25 67.42346.25 91.69158.92 55.58168.22 43.09rtpp*62.83 19.9352.49 17.7943.85 24.2877.73 29.5757.01 21.3948.19 18.1585.52 39.8966.28 25.9465.20 27.81lhpp*305.89 85.11120.03 40.14127.96 42.27321.21 88.04130.64 57.14130.03 92.82321.91 94.82146.31 65.99166.83 88.00ltpp*71.47 25.2454.61 24.8141.93 17.0567.99 37.9858.01 24.6143.75 17.4792.15 38.3757.52 25.0761.00\n 21.22r / lhpp : right / left hip pressure peak pressure ; r / ltpp : right / left thigh pressure \n peak , * p<0.05 and 3table 3.mean pressure distribution according to wedge height and cushion type ( n=36 , \n mmhg)firm surface5 cm gel cushion5 cm foam cushion3 cm wedge5 cm gel cushion with 3 cm wedge5 cm foam cushion with 3 cm wedge6 cm wedge5 cm gel cushion with 6 cm wedge5 cm foam cushion with 6 cm wedgetpm*59.09 10.2937.86 9.2429.45 9.3057.00 11.4939.14 6.5029.60 6.4360.45 10.0441.70 7.1330.92 8.52rhpm*85.04 17.6249.76 15.3939.41 13.0484.55 19.6454.74 14.0541.80 12.7288.61 18.3067.02 48.0342.65 15.67rtpm*31.88 11.7325.45 12.4117.78 7.1127.04 9.8524.93 6.6818.81 5.5629.26 9.3225.31 7.5822.59 19.51lhpm*85.86 16.4349.53 16.4142.53 18.7287.96 17.4967.39 6.0842.58 16.9288.68 17.0258.01 17.4545.83 17.91ltpm*30.84 11.1325.92 8.1218.19 6.9227.07 9.3426.61 6.7219.15 5.8129.06 9.6526.43 7.9027.71 8.02tpm : total pressure mean ; r / lhpm : right / left hip pressure mean ; r / lhpp : right / left \n hip pressure peak , * p<0.05 ) .\nr / lhpp : right / left hip pressure peak pressure ; r / ltpp : right / left thigh pressure \n peak , * p<0.05 tpm : total pressure mean ; r / lhpm : right / left hip pressure mean ; r / lhpp : right / left \n hip pressure peak , * p<0.05\nprolonged mechanical loading can lead to breakdown of the skin and underlying tissues , \n which can , in turn , develop into a pressure ulcer13 .\nit may be caused by inadequate blood supply and resulting \n reperfusion injury when blood re - enters the tissue .\nwhen sitting in the same position for \n extended periods , the dull ache experienced is indicative of impeded blood flow to affected \n areas .\nthe shortage of blood supply may lead to tissue damage and cell death within 2 h14 .\none of the assessment factors relating to \n the prevention of pressure sores is the pressure of cushions on clients15 .\nthe benefits of pressure relief and/or redistribution in minimizing pressure - related health \n risk ( including of pressure ulcer ) , among other issues , have been well documented .\nhowever , few studies have offered information on the \n combination effects of cushions with anterior wedges . hence , the objective of this study was \n to evaluate pressure redistribution effects on the user cushion interface pressure of \n healthy volunteers in their 20s when applying different cushions , including a firm surface \n with and without different height anterior wedges .\nour results show that the mean and peak pressures were greatest when sitting without a \n cushion with 3-cm and 6-cm anterior wedges and without anterior wedge compared with the \n other sitting arrangements .\nthe mean pressure in the hip was the highest when sitting on a \n 6-cm anterior wedge without a cushion , whereas the mean pressure in the thigh was the \n highest when sitting on a firm surface without an anterior wedge .\nin addition , the mean and \n peak pressures were the lowest when sitting on a foam cushion without an anterior wedge . \n\ngong and an reported that the mean and peak pressures were the lowest when a 6-cm anterior \n wedge was used . however , in this study , these two variables were the lowest when sitting on \n a foam cushion without an anterior wedge11 .\nthe participants of this study sit with the hip , knee , and ankle joint at \n an angle of more than 90. therefore , the sitting professional must assess posture before \n recommending the use of cushions and wedges .\nfrom the results , we presumed that the foam cushion could be the best choice for pressure \n redistribution .\nthese results suggest that people who sit , particularly those with diseases , \n seek out professional support in choosing the appropriate cushion and height of their chair \n based on their needs .\nthe present study only compared the performance of two cushions , including a firm surface , \n and two types of anterior wedges , in redistributing user \nhence , the number of participants , cushions , and wedge types , as well \n as the height of the cushion and wedges , must be expanded for generalization in future \n studies .\ncushion \n interface pressure redistribution , the relationship between sitting positions and interface \n pressure redistribution must be investigated .\nas the proper cushion types and anterior \n height wedges for people with or without diseases , such as stroke , spinal cord injury , and \n muscular dystrophy , must be established , this study establishes important guidelines for \n future research for establishing a sitting environment .", "answer": "[ purpose ] the purpose of this study was to investigate interface pressure redistribution \n in healthy volunteers when applying different cushions and anterior wedge heights . \n [ subjects and methods ] this study included 36 healthy individuals in their 20s . \n the peak \n and mean pressures were measured by applying different cushions and anterior wedge \n heights . \n the results were analyzed by using a one - way analysis of variance and post - hoc \n analysis . \n [ results ] the peak and mean pressures were statistically significant based on \n the cushion types and anterior wedge height . \n the peak pressure was at its highest and \n lowest when sitting on a 6-cm anterior wedge and a foam cushion , respectively . \n the mean \n pressure was greatest when sitting on a 6-cm anterior wedge of a firm surface and smallest \n when sitting on a 5 cm foam cushion . \n [ conclusion ] this study shows that the most effective \n method for pressure redistribution was sitting on a 5 cm foam cushion without an anterior \n wedge .", "id": 855} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese lesions though may cause life threatening hemorrhage , watchful observation is still considered as a treatment option in these patients .\na 71-year - old male presented with pulsatile swelling over the right side of face and over the forehead in october 2009 .\npatient is a known diabetic and hypertensive for the past 9 years on regular medications .\npatient was evaluated with computed tomography ( ct ) angiogram , which showed aneurysm of the external carotid artery with thrombus within and multiple aneurysm of the branches of external carotid arteries .\ntreatment option of excising the aneurysm with ligation of external carotid aneurismal branches was discussed with the patient . since the swelling was asymptomatic for the past 34 years , patient was not willing for any procedure .\nhe is assessed with clinical examination on each visit and ultrasound examination performed once in a year to assess the size of the aneurysm .\nthe patient has been on follow up for the past 4 years without any new symptoms or increase in size of the aneurysm .\naneurysm of the external carotid artery and its branches have been described in cases due to trauma , iatrogenic injury , dental extraction , and also due to head and neck cancer because of tumor infiltration or due to radiation therapy .\ngeriatric patients with aneurysm are first consulted by a primary care physician and hence primary care physician at the community level has a major role in following these patients and referring these patients to specialized vascular centre .\nincrease in size of the aneurysm or impending rupture necessitates the need for referral to specialized center .\nthe need for surgical intervention or endovascular stenting does not arise in our patient who has this aneurysm for 34 years and was on follow up for the past 4 years without any symptoms [ figure 1 ] .\npulsatile swelling over the face , forehead , and scalp in this setting , the role of primary care physician is important to decide upon surgical or conservative management after having discussion with the patient .\nmultiple aneurysm of external carotid artery this case was discussed for the rarity of idiopathic multiple aneurysm [ figure 3 ] of the external carotid artery [ figure 4 ] and the need for individualized treatment protocol to be followed , as in this case , only watchful observation . in this world of evolving surgical techniques and newer treatment modalities , conservative treatment still has a role to play .\neven in the era of advanced medical technology practices , treatment should be individualized and the choice rests with the patient .\nprimary care physicians have a major role in follow up of these patients and decide upon referring these patients to specialized vascular center thus lessen the burden of vascular centre in following these patients .", "answer": "aneurysms of external carotid artery are rare . \n treatments for these are undertaken for the prevention of complications like hemorrhage or rupture , and embolism . \n we present a 71-year - old male with idiopathic multiple aneurysm for the past 34 years on conservative management and regular follow up for the past 4 years . \n this case was discussed for the rarity of idiopathic multiple aneurysm of the external carotid artery and the need for individualized treatment protocol to be followed as in this case , only watchful observation considering the age and patient compliance . in this world of evolving surgical techniques and newer treatment modalities , conservative treatment still has a role to play . \n primary care physicians at the community level have a major role in following these patients and referring them as and when the need arises .", "id": 856} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nvarious -glucans have been extracted from various sources such as fungi , baker 's yeast , barley , oats , and seaweed .\nthe physicochemical properties of -glucans differ depending on characteristics of their primary structure , including linkage type , degree of branching , molecular weight , and conformation ( e.g. , triple helix , single helix , and random coil structures ) [ 1 , 2 ] .\n-glucans extracted from barley , which mainly contains -(1,3 - 1,4)-d - glucan , have been demonstrated to reduce blood lipid levels , including cholesterol and triglyceride levels [ 35 ] .\nthe mechanisms by which -glucans reduce blood lipid levels have been shown to include prevention of cholesterol reabsorption by adsorption , elimination of bile acid by adsorption , an increase in bile acid synthesis , and suppression of hepatic cholesterol biosynthesis by short - chain fatty acids produced by fermentation with intestinal bacteria [ 68 ] .\nclaims that barley products reduce the danger of coronary heart disease have been endorsed by the food and drug administration of the united states .\nin addition , -glucans extracted from barley have also been reported to possess various other biologic activities , for example , reducing blood glucose level , enhancing insulin response , protecting against stress ulcers , and restraining allergic reactions .\nfurthermore , -glucans extracted from barley have been used in health products as a diet food , because glucan is a dietary fiber .\nthus , -glucans extracted from barley have been used extensively as supplements and food additives .\nwhole grain products are recommended for healthy diets , as they are recognized sources of dietary fiber .\nfurthermore , ragaee et al . demonstrated the antioxidant activity of various cereals such as barley , millet , rye , and sorghum .\noxidative stress is considered one of the primary causal factors for aging and various diseases such as arteriosclerosis , cardiovascular disease , cerebral diseases , diabetes , inflammatory diseases , and cancer [ 14 , 15 ] .\nit is thought that scavenging of reactive oxygen species ( ros ) is important for the prevention of these diseases .\nif it were to be shown that -glucan , a natural component of grain , exerts antioxidant activity , the utility of -glucan as a polymeric excipient for supplement or food additive would increase further .\ntherefore , the aim of the present study was to examine the antioxidant activity of -glucan to assess potential new health benefits associated with -glucan as a polymeric excipient for supplement and food additive .\nthe effects of the extraction source , extraction method , and molecular size of -glucan on antioxidant activity were also investigated .\nfurthermore , the antioxidant activity of -glucan was compared with that of polymers that are commonly used as food additives .\n\n -glucans extracted from barley using different extraction methods and of different molecular sizes , contained more than 70% -(1,3 - 1,4)-d - glucan ( figure 1(a ) ) , and -glucan isolated from black yeast ( aureobasidium pullulans ) , which contained more than 85% -(1,3 - 1,6)- d - glucan ( figure 1(b ) ) , were donated by adeka co. ( tokyo , japan ) .\n-glucan extracted from oats , with an unknown composition , was purchased from megazyme international ireland ltd .\ngelatin , pectin from apple , pectin from citrus , curdlan , gellan gum , and xanthan gum were purchased from wako pure chemical industrial ltd .\nconcentrations of 0.52.0 w / v% of -glucans or other polymers were prepared by dissolving the molecules in ion - exchanged water .\nchitosan was dissolved in 0.1 m acetate buffer solution ( ph 4.5 ) , because chitosan did not dissolve in ion - exchanged water .\nantioxidant activity against hydroxyl radicals in the solution was determined using a radical catch kit ( aloka co. ltd . ,\nthe kit measures the amount of hydroxyl radicals generated by the fenton reaction with hydrogen peroxide catalyzed by cobalt using luminol luminescence .\nbriefly , 50 l of cobalt chloride reagent , 50 l of luminal reagent , and 20 l of sample solution were mixed , and , after preincubation at 37c for 5 min , 50 l of hydrogen peroxide reagent was added .\nthe amount of luminescence generated from 80 seconds to 120 seconds after the addition of hydrogen peroxide reagent was detected with a luminescence reader ( accuflex lumi 400 ; alola co. ltd . ,\nwas estimated using the following equation : \n ( 1)radical scavenge ( % ) = amount of hydroxy radical scavengedamount of hydroxy radical generated100 . \n\nas shown in figure 2 , the hydroxyl radical scavenging activity of -glucan differed between different sources of -glucan . in particular , -glucan extracted from barley showed the strongest hydroxyl radical scavenging activity . on the other hand , the hydroxyl radical scavenging activity of -glucans extracted from black yeast or oats was fairly low .\nfurthermore , 0.1 w / v% of -glucan extracted from barley scavenged approximately 60% of the hydroxyl radicals in the system , and the hydroxyl radical scavenging activity of the -glucan increased gradually with an increase in -glucan concentration ( figure 3 ) .\n-glucans extracted from both barley or oats were found to comprise mainly -(1,3 - 1,4)-d - glucan ( figure 1(a ) ) . on the other hand , -glucan extracted from black yeast comprised mainly -(1,3 - 1,6)-d - glucan ( figure 1(b ) ) .\nin addition to these differences in linkage type , the properties of -glucans are influenced by the degree of branching , molecular weight , and conformation [ 1 , 2 ] .\nalthough the mechanisms by which -glucan scavenges hydroxyl radicals are not yet clarified , the different structures of -glucan , which may be associated with the source and extraction method of obtaining -glucan , may influence antioxidant activity . \n\nfirst , the barley was crushed and then extracted under neutral , acidic ( 50 mm citrate buffer aqueous solution ( ph 4.0 ) ) , or alkaline ( 50 mm carbonate buffer aqueous solution ( ph 9.0 ) ) conditions with warm water at 50c . after solid - liquid separation , the liquid phase was condensed .\nthe hydroxyl radical scavenging activity of -glucan extracted from barley using the different extraction methods is shown in figure 4 .\nthe hydroxyl radical scavenging activity of -glucans extracted under an acid condition or an alkali condition was slightly higher compared with that when -glucans were extracted under a neutral condition with warm water .\nthe -glucans extracted from barley used in this study comprised more than 70% -(1,3 - 1,4)-d - glucan , but also contained other components ( i.e. , proteins , lipids , saccharides , and dietary fiber ) .\nthe hydroxyl radical scavenging activity of almost pure -(1,3 - 1,4)-d - glucan , which was obtained by repeated recrystallization of -glucan extracted under neutral conditions with warm water ( 50c ) , was 43 1% .\nalthough the possibility that other components contributed to the radical scavenging activity of -glucan can not be completely ruled out , this finding shows that the greater part of the hydroxyl radical scavenging activity was caused by -(1,3 - 1,4)-d - glucan .\nhowever , -glucan extract is generally used without further refinement for supplements or food additives .\nthese findings demonstrate that -glucans extracted using a variety of extraction methods , from acidic to alkaline conditions , have high radical scavenging activity .\nthe molecular weight of -glucan extracted from barley with warm water is 40,000100,000 da ; the oligomer prepared from the macromolecule -glucan by enzymatic degradation with lichenase has a molecular weight of approximately 2,000 da ( as described by the manufacturer ( adeka co. , tokyo , japan ) ) .\nas shown in figure 5 , the hydroxyl radical scavenging activity of -glucan was reduced with a decrease in molecular size .\nhowever , antioxidant activity was reduced only by about half , even when molecular weight was reduced by about 1/201/50 .\nthis finding indicates that -glucan exerts hydroxyl radical scavenging activity across a wide range of molecular sizes . \nthe hydroxyl radical scavenging activity of various polymers was determined and compared with that of -glucan . in this experiment\n, the hydroxyl radical scavenging activity of 1% xanthan gum could not be determined due to its high viscosity ; therefore , 0.5% was used .\nas shown in figure 6 , pectin from apple or citrus , chitosan , and xanthan gum showed hydroxyl radical scavenging activity .\nhowever , the hydroxyl radical scavenging activity of each of these polymers , which are used as food additives , was inferior to that of -glucan extracted from barley .\nthe polymers pullulan , dextrin , and curdlan , which are copolymers of glucose , were also assessed .\npullulan is a linear -1,4 : 1,6-d - glucan consisting predominantly of repeating maltotrioses ( consisting of 3 d - glucose molecules linked with -1,4 glycosidic bonds ) linked by -1,6-glucosidic bonds .\ndextrin is also a -1,4-d - glucan or -1,6-d - glucan , whereas curdlan is a linear -1,3-d - glucan consisting of -(1,3)-linked d - glucose residue .\nhydroxyl radical scavenging activity was not observed for curdlan , though curdlan is a -glucan ; further , no antioxidative activity was observed for pullulan or dextrin .\nthis finding indicates that the hydroxyl radical scavenging activity of -glucan is affected by the primary structure of the molecule , including linkage type , degree of branching , molecular weight , and conformation .\nhydroxyl radicals have the strongest reactivity and oxidation power among ros . the ability to scavenge\nros is a precious property for the prevention of various diseases and aging . in this study\n, it was shown that -glucan extracted from barley exerts significant antioxidant activity , in addition to the various biologic activities previously described .\nthe amount of antioxidant activity of -glucan was influenced by the different physiologic properties ( e.g. , structure and molecular size ) of -glucan , which varied depending on the source and extraction method used .\nfurthermore , the hydroxyl scavenging activity of -glucan was significantly higher than that of various polymers that are used as food additives .\nthese results indicate that -glucan has promise as a polymeric excipient for supplement and food additive with antioxidant and other benefits , which may contribute to enhancing health and beauty .", "answer": "-glucans extracted from barley , which mainly contains -(1,3 - 1,4)-d - glucan , are used extensively as supplements and food additives due to their wide biologic activities , including a reduction in blood lipid level . in this study , \n the antioxidant activity of -glucan was examined to assess potential new benefits associated with -glucan , because oxidative stress is considered one of the primary causal factors for various diseases and aging . \n -glucan extracted from barley was found to possess significant antioxidant activity . \n the amount of antioxidant activity was influenced by different physiologic properties ( e.g. , structure and molecular size ) of -glucan , which varied depending on the source and extraction method used . \n the antioxidant activity of -glucan was significantly higher than that of various polymers that are used as food additives . \n these results indicate that -glucan has promise as a polymeric excipient for supplement and food additive with antioxidant and other benefits , which may contribute to enhancing health and beauty .", "id": 857} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalthough herpes simplex virus ( hsv ) infections are very common worldwide , herpes simplex encephalitis ( hse ) is a rare disease with an incidence of one case per 250,000500,000 individuals per year .\napproximately 50% of patients with hse are older than 50 years.1 cytomegalovirus ( cmv ) , another member of the herpesvirus family , is the most common cause of congenital infection , with a prevalence rate of 0.2%2.5% in all live newborns.2,3 in adults , most reported cmv infections are seen in immunocompromised patients such as those with hiv ( human immunodeficiency virus)4,5 and after chemoradiotherapy.6 in these cases , the patients were also co - infected with hsv . here ,\nwe present a patient with coinfection of cmv and hsv type ii ( hsv - ii ) , who was admitted to the hospital for acute psychotic symptoms , but never treated with immunosuppressants before this admission .\nfor acute psychotic symptoms of delirium , delusion of persecution , fidget , over - alertness , and aggressive behaviors , a 67-year - old chinese man was sent to the outpatient department of the shantou central hospital , guangdong province , people s republic of china , on october 15 , 2013 .\non october 14 , he became suspicious , had delusion of persecution , and ran around . on the same day , he was sent to the local hospital where a magnetic resonance imaging was performed showing multiple hyperintensities in the left occipital lobe and temporal lobes in the t2-weighted images ( figure 1a ) .\nin addition , multiple hyperintensity lesions were seen in the temporal and parietal lobes and demyelination lesions in the white matter surrounding the lateral ventricles in the fluid - attenuated inversion recovery images ( figure 1b ) .\nthen , the patient was referred to the shantou central hospital , affiliated shantou hospital of sun yat - sen university on october 15 . on examination ,\nbut , physical examinations showed no abnormalities ( normal blood pressure and there was no fever ) .\nthe positive and negative syndrome scale score was 109 ( positive syndrome score of 36 , negative of 14 , and general of 59 ) .\nthe patient had no history of head trauma and hospitalization for mental disorders or any tumors , according to the family members .\nemergency treatment was started with the administration of the tranquilizer sodium phenobarbital ( 100 mg ) to reduce dysphoria and aggressive behaviors , the mood stabilizer sodium valproate ( 100 mg , administered in two fractions ) to stabilize the mental state of the patient , and the antipsychotic olanzapine ( 10 mg , administered in four fractions ) for the delusion of persecution .\nin addition , along with supportive treatments ( piracetam 20 grams in 100 ml 0.9% sodium chloride ) , empirical administration of antiviral treatment ( ganciclovir 250 mg in 0.9% sodium chloride ) was instituted under suspicion of viral encephalitis .\non october 16 , a blood examination was performed which showed no anemia and leukocytosis , but presented a higher percentage of neutrophil number ( 80.60% ; reference range 40%75% ) , a lower percentage of lymphocytes ( 11.70% ; reference range 20%50% ) , very high levels of creatine kinase ( ck ; 619 u / l , reference range 0174 u / l ) and its isoenzyme ( ckmb ; 39 u / l , reference range 024 u / l ) .\nin addition , a higher level of c - reactive protein ( crp , 113 mg / l ; 08\nchest radiographs ( october 17 ) showed stale tuberculous lesions in the upper lobe of right lung .\non october 18 , while the psychotic symptoms were improved , rough breath sounds were heard in the lungs , suggesting the presence of an infection there .\ntherefore , the antibiotic treatment with piperacillin - tazobactam ( 4,500 mg in 0.9% sodium chloride ) was initiated while the other treatments continued . on the same day\n, an electroencephalogram was performed showing slow waves characterized by strong peaks of delta and theta frequencies in the frontal lobe of the right hemisphere ( figure 2 ) .\non october 19 , a susceptibility - weighted imaging was performed , which more clearly showed the stale hemorrhages in the frontal lobe of the right hemisphere ( figure 1c ) , in addition to those seen in the left occipital lobe and temporal lobes of both sides .\nthe outcomes of cerebrospinal fluid ( csf ) examination came out on october 20 , 21 , and 22 , respectively , showing blood cells in normal ranges , mild lower levels of chloride ( 117 mmol / l ; reference range 120132 mmol / l ) , and glucose ( 2.41 mmol / l ; reference range 2.84.5 mmol / l ) .\nno bacteria were found . but both anti - cmv igg and anti - hsv - ii igm were positive , supporting a diagnosis of coinfection with hsv - ii and cmv in the brain .\non october 28 , as required by the family members , the patient was discharged .\nhis psychotic symptoms were significantly improved as evidenced by the reduction of positive and negative syndrome scale from 109 to 71 ( positive syndrome score of 14 , negative of 13 , and general of 44 ) .\nthe patient continued the antiviral and antipsychotic treatments at home after the discharge from the hospital .\nhe died of progressive cachexia 4 months after the discharge ( february 26 , 2014 ) , although his psychotic symptoms did not relapse .\nthe ethics committee of the shantou central hospital did not require approval for this case study .\nexcept for one early case report,7 all other double infections of the central nervous system ( cns ) with cmv and hsv were reported in immunocompromised patients.46,8 the patient reported here had no history of being treated with immunosuppressants .\nhis blood examination showed normal cell count despite of the presence of anti - cmv igg and anti - hsv - ii igm in csf , which is in accordance with the reported evidence for increased production of antibodies against several neurotropic infectious pathogens including hsv - i , hsv - ii , and cmv , in the csf of individuals with bipolar disorder9 or autism spectrum disorders.10,11 the mild signs of cns inflammation in this patient may account for the absence of seizures and focal neurological signs although he presented primarily acute psychotic symptoms and mental status changes . in line with this patient with hsv - ii infection , neurological sequelae were more frequent among patients with hsv - i compared with those infected with hsv - ii.12 in addition , cmv encephalitis in immunocompetent individuals has been associated with mild signs of cns inflammation , including absent to moderate pleocytosis.1315 in contrast , cmv in immunocompromised patients was featured with more severe clinical manifestations.5,6,16 the pathological hallmark of hse is hemorrhagic necrosis in the medial part of the temporal lobes .\nin addition , adjacent areas such as the orbital surface of the frontal lobe and cingulate gyrus may be involved . in line with these ,\nmagnetic resonance imaging of this patient showed hemorrhages in multiple regions of the brain , including the right frontal lobe , left occipital lobe , and the temporal lobes of both sides .\nthe hemorrhage in the right frontal lobe may be related to the peaks of delta and theta frequencies seen in electroencephalogram of this brain region .\nin addition , this patient showed multiple small infarctions and demyelination in the white matter surrounding the lateral ventricles .\nthe multiple small infarctions may be the consequence of cmv infection . in line with this speculation , animal , and human studies1720\nhave shown the cmv - induced damage of microvascular endothelium , vasculitis , thrombotic occlusions , and hemorrhages .\nanother feature of this patient is a very high level of crp in his blood .\nthe co - existence of high crp level and the antibodies to cmv and hsv - ii reminded us of a recent human study , in which the crp level was strongly associated with viral detection rate and mixed viral / bacterial detection rate ; whereas the rate of bacterial detection was not associated with the crp level.21 more significantly , plasma crp was an independent predictor of mortality in patients with chronic obstructive pulmonary disease caused by virus infections.21,22 in summary , we present a case of a 67-year - old male with coinfection of cmv and hsv - ii and without history of being treated with immunosuppressants .\nthe presence of his psychosis symptoms and absence of neurological manifestations may represent the clinical features of coinfection of cmv and hsv - ii .", "answer": "herpes simplex encephalitis is a rare disease . in adults , most of the reported cytomegalovirus ( cmv ) \n infections are seen in immunocompromised patients . \n we present a case of 67-year - old chinese male with the coinfection of cmv and herpes simplex virus type ii ( hsv - ii ) . \n he had no history of being treated with immunosuppressants , showed symptoms of psychosis and was scored 109 on the positive and negative syndrome scale . \n this patient presented with a rare case of coinfection of cmv and herpes simplex virus type ii with psychotic symptoms .", "id": 858} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmaxillofacial injuries have the potential to cause airway compromise and are associated with pain and swelling causing difficulty in mouth opening , chewing and deglutition .\nit helps in intraoperative pain relief and also helps in early post operative rehabilitation of maxilla facial trauma patients\nmandibular nerve block is often performed for diagnostic , therapeutic and anesthetic purposes for surgery involving mandibular region .\nwe report a case where intraoperative and post - operative pain in a case of unilateral fracture mandible was effectively managed through intermittent mandibular nerve block via a catheter .\na 30-year - old male with right sided parasymphyseal fracture mandible was scheduled for open reduction and internal fixation .\nthe patient had difficulty in opening the mouth due to pain ( 3 cm ) .\ninformed written consent for the nerve block was obtained and visual analogue scale ( vas ) of 0 - 10 , was explained to patient . in the operation theater ,\nneuromuscular blockade was achieved with vecuronium and anesthesia was maintained with o2 and n2o using controlled ventilation .\nthe right side of the face was prepared for mandibular nerve block with lateral extraoral approach [ figure 1 ] .\narrow showing skin site of epidural needle insertion for mandibular nerve block an 18-gauge i.v .\ncannula was inserted at midpoint of lower border of the zygomatic arch and was advanced perpendicular to face until it contacted the lateral pterygoid plate .\nthe length of the cannula outside the skin was marked and cannula was redirected slightly posterior to reach behind the posterior border and was advanced further by 0.5 cm .\ncatheter was tunnelled subcutaneously and the filter was attached to its other end [ figure 2 ] . for surgical analgesia , a bolus dose of 4 ml of 0.25% bupivicaine was given through the catheter .\nfentanyl 1mg/ kg i.v . was given only when there was more than 20% increase in heart rate or blood pressure above base line .\nthe surgery lasted for 2 h. at the end of surgery , neuromuscular blockade was reversed and the trachea extubated .\nfollowing extubation , the patient was conscious and pain free and then shifted to ward .\npost operatively , he received 4 ml of 0.25% bupivacaine through the epidural catheter every 12 h for two days .\nvas score was measured immediately after surgery and thereafter at 1 , 2 , 4 , 6 , 12 , 24 , and 48 h respectively .\npatient was observed for numbness at the surgical site , need for rescue analgesia , complications ( nausea , vomiting ) .\nnumbness in area of lower jaw line was present throughout the period but subsided after discontinuation of local anesthetic through epidural catheter .\nhe was discharged on fourth post operative day with advice for follow up in o.p.d .\nmandibular nerve block can be used to manage intra as well as post operative pain in cases of fracture mandible .\nwe performed lateral extra oral approach because of restricted mouth opening and the need to retain the catheter for post operative analgesia .\n18 g cannula instead of epidural needle was used to minimize the bleeding from pterygoid plexus of veins .\nthe cannula was advanced further after contacting lateral pterygiod plate so that the catheter comes in vicinity of mandibular nerve and there is no displacement during jaw movements .\nthe catheter was further tunnelled subcutaneously to prevent dislodgement and filter was used to prevent infection .\nthere was excellent post operative analgesia achieved with this technique as shown in decreased pain scores , both static as well as dynamic .", "answer": "mandibular nerve block is often performed for diagnostic , therapeutic and anesthetic purposes for surgery involving mandibular region . \n advantages of a nerve block include excellent pain relief and avoidance of the side effects associated with the use of opiods or non - steroidal anti - inflammatory drug ( nsaids ) . \n a patient with maxillo facial trauma was scheduled for open reduction and internal fixation of right parasymphyseal mandibular fracture . \n the mandibular nerve was approached using the lateral extraoral approach with an 18-gauge i.v . \n cannula under general anesthesia . \n he received 4 ml boluses of 0.25% plain bupivacaine for intraoperative analgesia and 12 hourly for 48 h post operatively . \n vas scores remained less than 4 through out observation period . \n the only side effect was numbness of ipsilateral lower jaw line , which subsided after local anesthetic administration was discontinued . \n patient was discharged after four days .", "id": 859} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbalantidium coli ( b. coli ) is the only ciliated protozoan that is known to infect humans .\nbalantidiasis is a zoonotic disease occurring in humans via the feco - oral route from the normal host , the pig .\nhowever , it may be found in rare extraintestinal sites such as liver , lung , and genitourinary tract .\nb. coli can become an opportunistic parasite in immunosuppressed hosts living in urban environments , where pigs are not a factor in infection . in this case report\n, b. coli was incidentally found in the urine of a patient having chronic obstructive pulmonary disease ( copd ) who was on steroids for a long time .\nthe patient had no history of diarrhea , other gastrointestinal ( gi ) symptoms , previous urinary tract infection , or urethral discharge .\nhe was also taking bone broth / soup . as a routine work - up urine sample was received .\n, several oval - to - oblong ciliated parasites that were approximately 75 50 m in size were seen swimming rapidly across the slide [ figure 1a ] .\ntwo to three pus cells per high power field and few candidal pseudohyphae and spores were also present .\ncytosmears were prepared from the urine sediment to identify the morphology . both hematoxylin and eosin ( h&e ) and giemsa staining were done . in h&e\nstained smears [ figure 1b ] , cytoplasmic food vacuoles and macronucleoli were seen and faint impression of cilia was noted . in giemsa stained smears [ figure 1c and d ] ,\nthe parasite was identified and the body was covered with short and delicate cilia that were all of uniform length . to exclude contamination , we examined two repeat urine samples that were collected under sterile condition .\nbased on the morphology and swimming pattern , a diagnosis of urinary balantidiasis was made .\noval - to - oblong ciliated trophozoites containing cytoplasmic food vacuoles ( thin arrows ) .\n( b ) ( h&e , 40 ) trophozoites of b. coli in urine showing cytoplasmic food vacuoles and faint impression of cilia ( thick arrow ) .\n( c and d ) ( giemsa , 40 ) trophozoite of b. coli in urine covered with short and delicate uniform length cilia ( thin arrows ) complete hemogram and biochemistry profiles were within normal limits .\nserology for human immunodeficiency virus ( hiv ) and hepatitis b surface antigen ( hbsag ) were negative .\nhis fecal samples and bronchoalveolar lavage fluid samples were negative for trophozoites / cysts of b. coli .\nthe patient was very sick at the time of admission , later he was intubated and kept on ventilator .\nmalmsten was the first to recognize b. coli in two humans with dysentery in the year 1857 .\nthe pig is the common reservoir of infection but the parasite is harmless to the host as the parasite thrives mainly on starchy food that is abundant in pig 's intestine .\nthe scarcity of starchy food in the human bowel explains the rarity of balantidial infection in man .\ncyst is the infective stage , when ingested liberates trophozoites in the large intestine , which may remain in the bowel or may invade submucosal coat of the bowel .\nthe trophozoites and cysts of b. coli are shed in feces and if the cysts , in particular , contaminate drinking water or food , the infection can be spread to other pigs or humans .\nthe trophozoite measures 30 - 150 m in length and 25 - 120 m in width ; the cyst , which may be spherical or slightly ovoid , measures 40 - 60 m in diameter .\nthe mouth ( oral apparatus ) is located at the tapering anterior end , and the cytopyge ( anus ) is located at the rounded posterior end .\nbalantidium causes no serious disease of the gi tract ; however , in conditions such as malnutrition , alcoholism , or a compromised immune system , it can lead to disease . in our case , the source of infection is not clear .\nthe patient had no history of contact with pigs , but he had history of intake of bone broth .\nthird hypothetical possibility is the ascending infection from the urine pot that was washed with plain contaminated water .\nb. coli should be differentiated from trichomonas vaginalis ( t. vaginalis ) , entamoeba histolytica ( e. histolytica ) , ciliocytophthoria phenomenon . in urine\nit can be differentiated easily from b. coli by its morphology and motility . in stool ,\nit moves on the slide surface by means of an anterior ectoplasmic pseudopod and is smaller ( around 25 m ) in diameter .\nin addition , mature cysts are smaller and quadrinucleate as compared to binucleate b. coli cysts . in case of samples taken from anatomic locales that are lined by ciliated columnar epithelium\nciliocytophthoria are much smaller ( average 12 10 m ) anucleated cells with cilia along one edge\n. many cases of b. coli infection in the stool sample have been reported worldwide . however , in urine there were only a few case reports available .\nwe have found only two case reports of isolated urinary balantidiasis from india while the rest showed coinfection with t. vaginalis .\numesh reported a case of a 29-year - old woman with cystitis due to b. coli .\nreported urinary balantidiasis in a 68-year - old farmer having diabetes and chronic kidney disease .\nto the best of our knowledge , this is the third case report of isolated urinary balantidiasis from india .\nrapid spiraling motility and cytosmears stained with giemsa and h&e satins are very useful in morphological identification .\neffective sanitation , use of clean water , and consumption of properly cooked food are probably the most effective ways to prevent balantidiasis in humans .", "answer": "balantidiasis is a rare zoonotic disease in humans . \n balantidium coli is the causative ciliated protozoan . \n we present a case of urinary balantidiasis in a patient having chronic obstructive pulmonary disease ( copd ) who was on steroids for a long time . \n he has no symptoms of bowel or urinary involvement . \n we are reporting this case because of its rarity in human urine and also for future references .", "id": 860} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmalaria control programmes utilising indoor residual spraying are only effective if a high coverage of targeted structures is achieved and an insecticide that is effective against the specific mosquito vector is correctly applied .\nongoing monitoring of spraying operations is essential to assure optimal programme performance and early corrective action , where indicated .\nsuccessful development and application of a computerised spraying operations management system in mpumalanga province , south africa during 1998 resulted in its adaptation and introduction in neighbouring maputo province , southern mozambique during 2000 .\nthe structure and components of this computerised management system are described , and its ' operational benefit in southern mozambique , where community - based spray operators apply intradomiciliary insecticide , are reviewed .\nthe computerised management system allowed malaria programme management and field supervisors to monitor spraying coverage , insecticide consumption and application rates on an ongoing basis .\nthe system supported a successful transition to community - based spraying , while assuring correct insecticide application and spraying completion according to schedule .\nin 1946 , south africa introduced intradomiciliary spraying with residual insecticides , ddt ( dichlorodiphenyltrichloroethane ) and bhc ( benzene hexachloride ) , to kill indoor - resting vector mosquitoes and thereby control malaria .\nthis resulted in a 75 percent reduction in the geographic extent of the malaria - affected area , with malaria occurrence limited to summer epidemics in the low - lying northern and eastern border areas with botswana , zimbabwe and mozambique .\nsimilar malaria control programmes were initiated in other southern african countries . in mozambique , spraying operations for malaria control collapsed during the 1970s due to the protracted civil war with a resulting high burden of endemic malaria throughout the country .\nrecently there has been a resurgence of malaria in southern africa , attributed to a number of factors , including parasite drug - resistance , mosquito insecticide - resistance , climate changes and large - scale population migration .\nthe hiv / aids epidemic has resulted in a simultaneous dwindling of resources available for public health programmes , thus placing an onus on programme managers to ensure optimal efficiency of their activities .\nan efficient spraying programme is characterized by application of the correct volumes of insecticide on surfaces suitable for mosquito resting .\nthis should be achieved before the onset of peak malaria transmission with a high coverage of targeted structures .\na formal spraying management system was introduced in south africa for the first time in 1973 , with activity forms being completed by the field officials responsible for each spraying team and a \" hut - card \" left under the eave of each sprayed dwelling .\nthis was expanded to a set of seven different spraying record forms in 1975 under the auspices of the world health organization .\nthis set consisted of a spray operator record , a daily spray - team report , a weekly report , a monthly report , a locality completion report , a sector completion report and a spraying completion report .\nalthough this manual system was cumbersome it became entrenched , and remained essentially unaltered in south africa for more than 20 years .\na major flaw of this data system was that field staff were not trained to use the data for programme monitoring .\nthus serious programme deficiencies usually only became apparent at the end of the spraying season when the data were centrally analysed .\nmpumalanga province , located on the border with mozambique in the north - east of south africa , began to replace permanently employed spray personnel with temporary spray personnel recruited from each malaria - affected community .\none hundred community - based spray personnel were appointed , each accountable to their local community , and the team was responsible for spraying almost 170,000 structures during each annual spraying round . with supervisory support limited to one field manager and six field officers , it was postulated that unless an improved spraying management system was introduced , programme performance and efficiency might deteriorate .\na computerised management system was developed in mpumalanga province to enable malaria programme management and field supervisors to monitor , even on a daily basis when required , spraying coverage , individual spray operator 's performance , and insecticide consumption and application rates .\nthe success of this computerised management system resulted in it being extended to neighbouring swaziland and also to southern mozambique , where a malaria vector control programme was recently re - introduced through the multilateral lubombo spatial development initiative ( lsdi ) , a partnership between the governments of mozambique , swaziland and south africa .\nwe describe the structure and components of this computerised management system , and provide operational evidence of its value in the southern mozambique malaria control programme .\nthe computerised spraying management system in southern mozambique was designed prior to the first round of spraying early in 2000 .\nthe area targeted for spraying included the rural districts of namaacha and matutuine , and sections of the peri - urban districts of matola and boane in maputo province , covering an area of 7,962 square kilometres with an estimated 200,000 homes .\nthe management system comprises two platforms , a spraying database and a spatial mapping platform .\na microsoft access 2000 database was used with front - end data entry and output screens .\nthe data entry screen mirrors the manually completed weekly spraying form , which collates data from daily spraying report forms that are submitted each week by spray operators to their supervisor ( figure 1 ) .\n\" drop - down \" menus ensure speed , ease and accuracy of data entry .\na number of datasets have been integrated to form the basis of the spraying data base , including a comprehensive listing of place names to be sprayed , number of homes ( ministry of health database ) , demographic data for each electoral area ( 1995 electoral census by the department of planning and cooperation ) , spray operator identification codes and details of insecticides used during spraying operations .\neach record is automatically allocated a unique number and all information can be linked through a relational database to a specific spray operator , team , time - period or administrative area .\nadditional information collected includes the number of visits made to a specific house , reasons for not spraying ( where applicable ) , insecticide used by each spray operator and number of spray - can refills . data is automatically backed up after each day of data entry onto an external zip drive .\ndata entry screen of the malaria information system the geographic information system ( gis ) platform required both spatial ( roads , clinics , locality boundaries ) and attribute data ( locality or clinic names , population figures ) .\nthe gis software package mapinfo professional[mapinfo corporation , 4 global view , troy , new york , 12189 , usa .\n] was used and maps of southern mozambique ( scale 1:250,000 ) were obtained from the direco nacional de geografia e cadastro in maputo .\nthe south african medical research council digitally captured relevant geographical and cadastral features , including roads , rivers , towns and different administrative level boundaries .\nthe smallest administrative unit boundaries at which data was captured ( localities ) were drawn onto local maps by the staff of the ministry of health involved in the project and then digitally captured for inclusion in the gis display .\npreset queries , to generate standardized management reports , were planned and designed in partnership with field supervisors and programme management staff to meet their specific needs .\nhowever , the system was designed to allow user - friendly production of customized additional reports where required .\nspecific training was provided for programme supervisors on making sense of data and interpreting reports , with a spraying database manual developed for ready reference .\na major emphasis in training has been on identifying operational problems and implementing timely remedial action .\nas field managers enter the summary data at the namaacha field office on a weekly basis , necessary remedial action is taken within a week .\nthe ongoing monitoring of individual spray operator 's productivity , in terms of number of structures sprayed each day and volume of insecticide sprayed per structure , has facilitated early detection of operational problems , leading to prompt investigation and supportive corrective action by supervisors .\na standardized aid for evaluating individual operators ' spraying quality during field visits was designed and implemented .\nfield managers discuss evaluation results with spray operators on - site in order to eliminate mistakes .\nthe frequency of required supervisory corrective interventions has steadily decreased since the beginning of the programme and it is likely that some of this effect is due to the enhanced monitoring and response made possible by the computer management system .\ninsecticide application rates ( grams per square meter ) are constantly monitored for under- and over - application\n. under - application reduces insecticide residual activity and thus effectiveness , while over - application is wasteful . where sub - optimal application rates were detected , investigation included scrutiny of insecticide preparation , nozzle condition , application pressure , distance of nozzle tip from sprayed surface , and spraying rhythm .\nspraying coverage exceeded 90% of 222,000 structures in southern mozambique , a level that is considered more than adequate . in areas where the management system repeatedly identified lower coverage than expected , investigations were conducted to determine whether this was the result of diminished community support , absenteeism or poor motivation of the specific spray operator .\nmaps depicting the coverage achieved by each team proved useful to malaria control programme management for tracking teams ' progress , providing ongoing updates to senior health management and encouraging spray personnel to attain their target ( figure 2 ) .\nan example of a spraying progress map by locality in maputo province , mozambique , 2003 an additional benefit was that data captured during the first spraying round during 2000 was used to verify official data sources and provide actual household figures to replace official government estimates .\nthis provided more precise information for malaria control planning and demographic data needed by other government agencies for planning .\ncompetition for ever - dwindling public health resources is a major challenge for malaria control programmes in sub - saharan africa .\nconstant monitoring and evaluation of spraying activities is obligatory where indoor residual spraying is an important component of malaria control , to ensure effective application and prevent wastage .\ncomputerised management systems are proving useful tools for providing timely information to address potentially deleterious human , social and technical factors that could negatively impact on malaria control .\nthe computerised management system has been in operation for three years supporting the mainly rural vector control programme that now covers an area of 13,770 square kilometres in southern mozambique .\nnot only has it supported a successful and cost - effective transition to a community - based spraying approach , but it has also ensured that spraying was completed to schedule . the ability to immediately identify problems at the level of an individual spray operator and institute appropriate remedial action assured good coverage and programme efficiency .\nthe computerised management system is a useful method for enhancing malaria control by improving application of existing tools .\nnote : a powerpoint presentation providing more detail on the malaria management information system and database is available at .\nmb , bs , cm , jlg , dd conceptualised , developed and implemented the mpumalanga computerised management system prototype ; mb , bs , cm , bm adapted this system for application in maputo province , mozambique .\nall authors contributed to the review of the system and the preparation of this manuscript .", "answer": "backgroundmalaria control programmes utilising indoor residual spraying are only effective if a high coverage of targeted structures is achieved and an insecticide that is effective against the specific mosquito vector is correctly applied . \n ongoing monitoring of spraying operations is essential to assure optimal programme performance and early corrective action , where indicated.methodssuccessful development and application of a computerised spraying operations management system in mpumalanga province , south africa during 1998 resulted in its adaptation and introduction in neighbouring maputo province , southern mozambique during 2000 . \n the structure and components of this computerised management system are described , and its ' operational benefit in southern mozambique , where community - based spray operators apply intradomiciliary insecticide , are reviewed.conclusionsthe computerised management system allowed malaria programme management and field supervisors to monitor spraying coverage , insecticide consumption and application rates on an ongoing basis . \n the system supported a successful transition to community - based spraying , while assuring correct insecticide application and spraying completion according to schedule .", "id": 861} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe success of root canal therapy is dependent on understanding the anatomy of root and root canal morphology.1,2 awareness and understanding of the presence of unusual external and internal root canal morphology largely contributes to the successful outcome of the root canal treatment . in literature ,\ndescription of the mandibular first premolar is typically of a single - rooted tooth.3,4 two - rooted , three - rooted , and four - rooted varieties have also been reported , but are rare.5,6 the root frequently has developmental depressions or grooves on both the mesial and distal surfaces . according to slowey , the mandibular premolars may present the greater difficulty of all teeth for a successful endodontic treatment.7 a study at the university of washington in 1955 assessed the failure rate of non - surgical root canal therapy ( nsrct ) in all teeth .\nnumerous endodontic failures after a routine treatment and flare - ups during the course of nsrct are cited as evidence\n. it could be because of variations in root canal morphology and difficult access to additional canal systems.8 this case report presents a successful , non - surgical management of mandibular left second premolar with three roots and root canals and a first premolar with two roots using a cone beam computed tomography ( cbct ) .\na 31-year - old male patient was reported to the department of conservative dentistry and endodontics , mnr dental college and hospital with a chief complaint of pain and pus discharge in the lower left back tooth region since 3 months .\n, there was a gingival inflammation with recession in relation to tooth numbers 34 , 35 , 36 .\nelectric pulp testing and thermal testing of the teeth indicated non vitality of 34 , 35 , and 36 . a confirmatory diagnosis of acute apical abscess in relation to 34 , 35 , and 36 was established and endodontic therapy was planned .\nthe mesiodistal width of the crown is lesser than mesiodistal diameter of the root and for further confirmation a cbct ( gentex ) , was planned .\ncbct with a 3d reconstruction confirmed a three rooted 34 and two rooted 35 ( figure 1b - d ) .\n( a ) pre - operative radiograph showing first and second premolar and first molar .\nthe area was anaesthetized using 2% lignocaine with 1:80,000 adrenaline ( lignox ) and isolated with a rubber dam .\nan access cavity was prepared with a modification that it had a cut at the buccoproximal angle from the entrance of the buccal canals to the cavosurface angle , so that it is results in a t - shaped outline ( figure 2a ) .\na working length was determined with an apex locator ( root - zx ) ( figure 2b ) . with crown down technique , cleaning and shaping\nwere performed with twisted file and protaper rotary instruments ( dentsply mailfilter ) . abundant irrigation with 3% sodium hypochlorite solution is done .\nbiomechanical preparation is done up to f2 . before obturation irrigation with 17% , edta and saline are done .\nobturation is done with gutta - percha and resin sealer ( ah plus , dentsply ) by cold lateral condensation ( figure 2c ) .\nthe coronal access was restored with resin composite ( 3 m espe ) ( figure 2d ) .\nsuccessful and predictable endodontic treatment requires knowledge of biology , root canal anatomy , and careful radiographic evaluation in order to determine number of roots and root canals .\npreoperative parallel radiographs , as well as mesial or distal angled radiographs , can help to determine number of roots .\nthe diagnosis and management of extra roots or root canals in mandibular premolars pose an endodontic challenge .\nfailing to locate and obturating a root canal is the major cause of failure in endodontic therapy .\nhoen and pink found 42% incidence of missed roots or canals in the teeth that needed retreatment.9 according to cleghorn , the incidence of three rooted mandibular first premolars is 0.2%.10 hence , it is import that all the canals be located and treated during the course of nonsurgical endodontic therapy .\nrodig and hulsmann have reported a case of mandibular second premolar with three separate roots and root canals diagnosed using intraoral periapical radiographs.2 wong and al - fouzan have published cases of mandibular second premolars with four canals.11,12 tzanetakis et al .\nhave reported endodontic management of mandibular second premolar with four root canals diagnosed with the aid of operating microscope.13 it has been established that a root with a tapering canal and a single foramen is the exception rather than the rule .\nserman and hasselgren ( 1992 ) reported a high incidence of multiple roots ( 18.1% ) and root canals in mandibular premolar teeth in a series of radiographic surveys with mandibular first premolars involved in 15.7% of patients and mandibular second premolars in 7% of patients.14 studies by lu et al .\nare similar to slowey suggestions that mandibular premolars are the most difficult to treat endodontically and also the apical configuration of these teeth was found to be complex.15 thus , a careful understanding and diagnosis of canal anatomy is of utmost importance for successful management of such cases .\naccurate preoperative radiographs of good quality along with an occlusal view , into the access opening and down the chamber of a mandibular premolar tooth , rarely shows any chamber floor , even when a suspected bifurcation of the canal is seen on the radiograph .\nthe surgical operating microscope sometimes aids in canal visualization of a canal system branching off the main canal . a fine , curved stainless steel file with a good tactile sense is the best guide to the detection of the accessory canals.16 a modification in the access cavity preparation is often needed for unhiding the additional orifices of the root canals or the orifices of the extra roots for a better instrumentation . when present the roots are usually mesiobuccal , distobuccal , and a lingual root .\nat least two radiographs , with the second radiograph angulated from 15 to 20 either mesial or distal from the horizontal long axis of the root , are required to reliably diagnose more than one root or root canal system in premolar teeth .\na sudden narrowing of the main canal on a parallel radiograph was a good criterion to judge root canal multiplicity.17 however , martinez - lozano et al .\nrecommend up to 40 mesial angulation from horizontal as more reliable in identifying the extra canals.18 deviation of the x - ray angle from the vertical axis of 15 to 30 was effective only in the mandibular first premolar in helping to visualize canal anatomy of premolar teeth .\ndyes , fiber - optic transillumination , magnifying loupes , and sodium hypochlorite bubbling in the extra canals help in locating additional canals . with the advent of advanced imaging techniques , an understanding of complex anatomies\ncbct is better of digital radiographic techniques in identifying multiple root canal systems in the mandibular incisor , mandibular first premolar , and maxillary first molar teeth.19\nmanagement of teeth with morphological variations presents a challenge , which requires proper instruments and the knowledge to use the instruments effectively .\nadvanced imaging techniques like cbct are valuable tools in diagnosing and managing cases , which deviate from the regular pattern .\nthe present case report emphasizes the need to understand , interpret , and manage a three rooted mandibular first premolar with three roots which has been successfully managed using cbct .", "answer": "understanding the morphological anatomy of the root and root canal systems of the teeth increases the success rate of endodontic therapy . \n advanced diagnostic imaging techniques like cone beam computed tomography ( cbct ) are an essential aid in understanding the anatomy of teeth especially in mandibular premolars . \n most commonly mandibular first and second premolars have a single root and a single canal . \n however , multiple root and canals have also been reported . \n the present case report discusses endodontic management of a three rooted mandibular first premolar using cbct .", "id": 862} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nMultiple hydride reduction pathways in isoflavonoids\n\nPaper sections:\nBackground\nThe reduction of isoflavones 1 has been actively studied during the last twenty years, owing to the range of interesting biological effects [1][2][3] -estrogenic activity, promise in cancer, osteoporosis, and coronary heart disease prevention -shown by the isoflavones themselves and their reduced metabolites. There are some reports [4][5][6][7][8] of total syntheses of reduced isoflavonoid structures from commercially available starting materials but overall yields in these multistep procedures tend to be low, and free hydroxy groups are not compatible. Another strategy involves the hydrogenation of isoflavones using a palladium or platinum catalyst but mixtures of reduction products are often formed [9,10]. Certain hydride reagents have been tested, as discussed below, for the reduction of simple or protected isoflavones but many of the early results are contradictory or rely on indeterminate product characterization.
The reduction of simple (nonflavonoid) \u03b2-alkoxy-\u03b1,\u03b2-unsaturated ketones by hydride reagents (NaBH 4 , LiAlH 4 , DIBAH) occurs normally by 1,2-attack, this being a key step in the well known \"carbonyl transposition\" of 1,3-diketone enol ethers into enones (R 3 O-CR=CR 1 -COR 2 \u2192 R-CO-CR 1 =CHR 2 ). [11][12][13][14][15] Prior to our work there were no reports on the reduction of isoflavones containing free hydroxy groups which nevertheless are common, usually at one or several of the C-5, C-7 and C-4' sites, in the naturally occurring isoflavonoids. It is to be expected that the presence of the phenolic hydroxyls, or the derived phenolate anions, will alter the reactivity pattern of the parent isoflavone system, besides perhaps decreasing the overall reactivity due to solubility reasons. For example, any tendency of hydride attack at the C-2 will be opposed by electron feeding from the 4'-OH group while an OH group at C-5 or C-7 will discourage attack at C-2 and C-4. Thus there was ample room for the development of reliable methods for the synthesis of hydroxy-substituted isoflavone metabolites, and for clarification of the course of reduction of isoflavones with various hydride reducing agents. We present here experimental details of our own results in this field together with a thorough survey of the literature. The discussion is based on the types of reduced isoflavonoid structures formed (Figure 1), i.e., isoflavanones 2, cis-isoflavan-4-ols 3, trans-isoflavan-4-ols 4, the ring opened \u03b1-methyldeoxybenzoins 5 and 1,2-diaryl-2-propen-1-ols 6, and isoflavenes 7 and 8 (hydride reductions do not lead to isoflavans 9, which however are obtained by catalytic hydrogenation [10,16,20]). Incidentally, it is appropriate to point out that flavones do not undergo similar reductive metabolism in mammals as described above for isoflavones. We will nevertheless present at a later date certain findings on the hydride reduction pathways in flavones.
\n\nResults and Discussion\nIsoflavanones (2) Isoflavanones result from the 1,4-reduction of isoflavones. The resonance contributor 10 will encourage this mode of attack. DIBAH, normally a preferential 1,2-reducer, reacts with methoxy-, benzyloxy-, MOMO-and MEMO-substituted isoflavones to give the isoflavanones in 40-93% yield [16,[21][22][23] (Table 1). Our own work has shown that even unprotected hydroxy-substituted isoflavones are reduced by a large excess of DIBAH in 50-70% yield (Table 1). The simple borohydride reagents reduce isoflavones to the isoflavanols (see below) but the Selectrides \u00ae give 60-88% yields of isoflavanones in the absence of hydroxy substituents according to our results (Table 1). There is no significant difference between the K-and L-Selectride \u00ae . In the literature, there is an isolated report of the reduction of a MOM substituted isoflavone by L-Selectride \u00ae in 40% yield (Table 2) [16]. Methoxy substituted isoflavones have also been reduced by sodium hydrogen telluride to give isoflavan-4-ones in 61-71% yields [24]. trans-isoflavan-4-ols 4 (Table 3). [16,29,34] Isoflavanones are reduced by electrophilic hydrides (borane-tetrahydrofuran, bistert-butylthioethane borane) diastereoselectively to cisisoflavan-4-ols, but a large excess of the reducing agent is usually needed [29].
Although it was realized by the early workers that diastereomeric mixtures of isoflavanols would presumably be formed, there were no reliable methods to determine their structures. In some papers, the products are summarily assigned the cis [25,26] or trans [35][36][37][38] structures. However, rigorous NMR analysis has recently made it possible to establish cisand trans-structures for the isoflavanol products and to study their conformational equilibria [32,34]. Borohydride reductions generally give a small preference for the cis products as suggested by Cram's rule [39]. We are not aware of any examples in the literature of single enantiomers of isoflavanone or isoflavanol metabolites, nor have such compounds been reported as hydride reduction products of isoflavones. In view of the significant biological properties of the reduced metabolites it will be interesting to examine the behaviour of the pure enantiomers.
\n\n2-Isoflaven-4-ols (11)\nThere are very few reports of this class of compounds, either from reductive processes or otherwise. In 1965, the reduction of the parent isoflavone by NaBH 4 in EtOH or diborane in THF was claimed [28] to furnish 2-isoflaven-4-ol in 75-76% yield, but unfortunately the characterization of this product relied on elemental analysis only. More recently, Japanese workers [40] reported that the reduction of 12 (Figure 2) by NaBH 4 in the presence of PdCl 2 in THF-H 2 O gave a 1:1 mixture of the ketone 13a and the diol 13b (Figure 2). A 1 H NMR spectrum was given for the latter isoflavenol but there appear to be certain discrepancies, notably in the \u03b4 value (8.69) reported for the H-8 which is some 2 \u03b4 units in excess of what would be expected for such a vinyl ether proton. Thus more work is required to fully confirm the nature of this class of reduction products. In the event, in our studies the reduction of isoflavone 1a by NaBH 4 in the presence of PdCl 2 in THF-H 2 O gave a 82:18 mixture of cisand trans-isoflavan-4-ol 3a, 4a while no 2-isoflaven-4-ols were observed. The absence of such 1,2-reduction products, or structures conceivably derivable thereof such as 2-or 3-isoflavenes (7,8), even in the CeCl 3 -complexed NaBH 4 reductions, must reflect the good stabilization obtainable via resonance heteroring stabilization (10) in the isoflavones. As already mentioned, this is in contrast to the behaviour of simple nonflavonoid \u03b2-alkoxy-\u03b1,\u03b2-unsaturated ketones which prefer 1,2attack by hydride.
Isoflavenes (7,8) and isoflavans (9) In the early work, [41] there is a mention of 7,4'-dimethoxy-2methyl-3-isoflavene being obtained in 15% yield from the reduction of the corresponding isoflavone by LiAlH 4 in Et 2 Obenzene but there is no structural data on the product other than elemental analysis, itself quite accurate. Similarly 2',4'dimethoxy-3',6,7-trihydroxyisoflav-3-ene was reported from the reduction of 2',4'-dimethoxy-3',6,7-trihydroxyisoflavan-4-one with LiAlH 4 in low yield [42]. More recent work by us [43] and others [16,44] would indicate that the normal course of LiAlH 4 reduction of isoflavones leads to deoxybenzoins and propenols (see below and Table 4).
Published syntheses of 2-and 3-isoflavenes involve the reduction of 3-arylcoumarins, [45][46][47] the corresponding aldehyde hemiacetals, [7] isoflavylium salts [48][49][50] or of isoflavones by the Clemmensen reaction [51]. Low-yielding non-reductive routes to 2-and/or 3-isoflavenes have also been reported [52,53]. 2-Isoflavenes 7 however remain mostly poorly character-ized, and some of the NMR spectral details reported [7,51,52] appear inconsistent with the 2-isoflavenoid structure. As far as the NMR spectra of 2-isoflavenes are concerned, a recent study clears this issue by 2D NMR work on a natural 2-isoflavene, [54] establishing that the H-2 and H-4 protons appear at \u03b4 6.87 and 3.61, respectively, much as expected by correlation data shift calculations. Isoflavans (9) have not been prepared by hydride reductions, but by catalytic hydrogenation of isoflavones [10,[16][17][18][19][20].
Deoxybenzoins ( 5) and propenols (6) Isoflavanones undergo a facile retro-Michael-type ring opening [21,55] under basic conditions to give the propenone intermediate 14 (Figure 2), sometimes considered [56] to be an independent isoflavone metabolite but presumably just an artefact in reality. As regards the synthesis of isoflavanones by DIBAH reduction of isoflavones (see above), we found that unless the workup is done with cold methanolic HCl, some amount of the propenone 14 will be formed and reduced further to the deoxy-benzoin 5. If on the other hand the deoxybenzoins are the actual synthetic targets, the reducing agent of choice is LiAlH 4 in THF. This works very well for isoflavones bearing a hydroxy group at C-7 such as genistein, but in isoflavones lacking a 7-OH group another reaction pathway competes leading to the propenols 6 [43] as byproducts (see below). We have discussed a possible mechanism to explain these hydroxyl-dependent divergent pathways [43].
To summarize, all hydride addition reactions with isoflavones appear to involve an initial 1,4-addition to give the isoflavanone enolate. In a hydroxylic solvent, or even on workup under basic conditions, the ketone is generated, and reduced further to the saturated alcohol (NaBH 4 ). In a nonprotic solvent, the \u03b2-aryloxyenolate will undergo a retro-Michael addition, giving the phenolate anion of the ring opened 2-propen- The dietary isoflavonoids are mainly metabolized in man via reductive pathways, leading to the reduced structural types discussed above (Figure 3). These compounds are often more estrogenic than the starting isoflavones. Research interest in many fields including medicine, nutrition and biosynthesis and metabolism thus converge on the reduced isoflavonoids. The work described in this paper shows that most structural types of reduced isoflavonoids are now reliably available in satisfactory or good yields by hydride reductions. Although not discussed here, it is clear that D atoms may be introduced in the same way which is very useful in the quantitation of the naturally occurring compounds by GC-MS selected ion monitoring techniques [61].
\n\nSupporting Information\nSupporting Information File 1
Experimental details and characterisation data.
[http://www.beilstein-journals.org/bjoc/content/ supplementary/1860-5397-2-16-S1.doc]
", "answer": "BackgroundIsoflavonoids are of interest owing to their appearance in metabolic pathways of isoflavones, and their estrogenic and other physiological properties, making them promising lead compounds for drug design. ResultsThe reduction of isoflavones by various hydride reagents occurs by a 1,4-pathway in contrast to ordinary \u03b2-alkoxy-\u03b1,\u03b2-unsaturated ketones. Isoflavan-4-ones, cisand trans-isoflavan-4-ols, \u03b1-methyldeoxybenzoins or 1,2-diphenylprop-2-en-1-ols are obtained depending on the hydride reagent, mostly in good yields. The stereoselective reduction of isoflavan-4-ones is also discussed. ConclusionThe work described in this paper shows that most structural types of reduced isoflavonoids are now reliably available in satisfactory or good yields by hydride reductions to be used as authentic reference compounds in analytical and biological studies.", "id": 863} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmusicians often experience musculoskeletal pain as a result of lengthy and long - term \n instrument performance .\nmore students enrolled in music schools note upper limb pain \n compared with students enrolled in ordinary schools1 .\nit has also been reported that the incidence of upper limb pain is \n higher in those who have longer practice times .\ntherefore , it can be said that upper limb \n pain in musicians is a symptom of overuse , with lengthy and long - term instrument performance \n being contributing factors .\nmusculoskeletal pain in musicians is common not only in the \n upper limbs but also in the lumbar and cervical regions , as well as in the shoulder \n girdle2 .\nfor example , it is conceivable that when playing a heavy instrument \n such as the tuba , a large load is applied to the trunk to maintain the performance posture . \n\nfurthermore , as instruments in a marching band are played while marching , a large load is \n probably also applied to the lower limbs .\nhowever , the performance postures \n of various types of instruments have not been sufficiently investigated .\nthus , the present \n study clarified the characteristics of the standing performance posture for the trumpet and \n the marching euphonium and investigated the effect of the performance postures of these \n instruments on the lower limb musculoskeletal system .\nthe subjects were 10 female university students in japan . their ( mean sd ) age was 20.5 \n 1.3 years , their height was 159.6 6.2 cm , and their weight was 55.1 7.2 kg .\nbecause the subjects were not \n professional trumpet or marching euphonium performers , they all received sufficient \n instruction from the instructor regarding the trumpet and marching euphonium performance \n posture prior to measurements .\nthe purpose and contents of the study were sufficiently \n explained to the subjects , whose consent to participate in the study was obtained . \n\nadditionally , approval was obtained from the shijonawate gakuen university ethics committee \n ( approval number 23 - 2 ) .\nthe subjects adopted a closed - leg resting standing position , a trumpet performance posture , \n and a marching euphonium performance posture .\nall instrumental performance postures were \n adopted in the standing , and the subjects focused directly ahead on a mark positioned at eye \n level . subjects maintained performance posture without actually playing the instrument .\nthe \n angle and muscle activity of the trunk and lower limbs were measured while the postures were \n maintained .\nthe measurement was performed in the sequence of the resting standing position , \n the trumpet performance posture , and the marching euphonium performance posture .\nthe trunk \n and lower limb angles were measured using a three - dimensional motion analysis device \n ( cms - hs , zebris medical gmbh , isny , germany ) .\nmarkers were attached to the lateral \n malleolus , lateral epicondyle of the femur , greater trochanter , and acromion on the left \n side of the subjects .\nthe sampling frequency was 100 hz , and the measurement time was 10 s. \n measurements were performed as soon as the subjects could maintain a stable performance \n posture .\nthe collected data were processed by image analysis software ( win - date , zebris \n medical gmbh ) , and the angles of knee flexion , hip flexion , and anterior tilt of the trunk \n were calculated .\nthe angle of knee flexion was considered as the angle formed between the \n line linking the lateral malleolus and the lateral epicondyle of the femur and the line \n linking the lateral epicondyle of the femur and the greater trochanter .\nthe angle of hip \n flexion was considered as the angle formed between the line linking the lateral epicondyle \n of the femur and the greater trochanter and a vertical line .\nthe anterior tilt angle of the \n trunk was considered as the angle formed between the line linking the acromion and the \n greater trochanter and a vertical line . a surface myograph ( myosystem 1200 , noraxon inc . , \n\nthe muscle activities measured \n were those of the cervical paraspinal muscles , upper fibers of the trapezius , lumbar \n paraspinal muscles , gluteus maximus , rectus femoris , biceps femoris , and lateral head of the \n gastrocnemius on the left side .\nafter treating the skin sufficiently to create a skin \n resistance of no greater than 10 , electrodes ( blue sensor p-00-s , ambu a / s , ballerup , \n denmark ) were attached parallel to the muscle fibers at the center of each muscle .\nspacing between the electrodes was 25 mm , the \n sampling frequency was 1,000 hz , and the sampling time was 10 s. measurements were performed \n as soon as subjects could maintain a stable performance posture .\nthe collected data were \n subjected to full - wave rectification using electromyogram analysis software ( myoresearch , \n noraxon inc . ) , and the average amplitude of the central three seconds was determined .\nthe \n average amplitude of each muscle was normalized as 100% according to the average amplitude \n of the 3-s maximum voluntary contraction .\nstatistical analysis entailed a one - way analysis of variance and multiple comparison using \n tukey 's method .\nmean sd . a : significant difference between the standing position and the trumpet \n performance posture ( p<0.01 ) .\nb : significant difference between the standing position \n and the marching euphonium performance posture ( p<0.01 ) .\nc : significant difference \n between the trumpet performance posture and the marching euphonium performance posture \n ( p<0.05 ) mean sd .\na : significant difference between the standing position and the marching \n euphonium performance posture ( p<0.01 ) .\nb : significant difference between the \n standing position and the marching euphonium performance posture ( p<0.05 ) .\nc : \n significant difference between the trumpet performance posture and the marching \n euphonium performance posture ( p<0.01 ) the anterior tilt angle of the trunk decreased significantly in the trumpet and marching \n euphonium performance postures compared with the resting standing position , as well as in \n the marching euphonium performance posture compared with the trumpet performance posture \n ( table 1 ) .\nthe muscle activity of the cervical \n paraspinal muscles , upper fibers of the trapezius , and lumbar paraspinal muscles increased \n significantly in the marching euphonium performance posture compared with the resting \n standing position , as well as in the marching euphonium performance posture compared with \n the trumpet performance posture ( table 2 ) . \n\nhowever , there were no significant differences in other measurement items between the \n postures .\nthe anterior tilt angle of the trunk can be rephrased as an increase in the posterior tilt \n angle of the trunk .\nthis is likely a means for maintaining the combined center of gravity of the \n instrument and the body in the most stable position possible .\nan increase in the posterior \n tilt angle of the trunk increases the lumbar lordosis angle .\nthis increase results in \n tension being applied to the anterior tissues of the lumbar spine , such as the anterior \n longitudinal ligament , and compressive force being applied to the zygapophyseal joints4 .\nchristie et al . reported that an increase \n in the lumbar lordosis angle while standing is associated with chronic low back pain5 .\nconsequently , maintaining the performance \n posture for the trumpet and the marching euphonium for a long period can contribute to low \n back pain .\nno significant difference was found in the muscle activities of the lumbar paraspinal \n muscles between the resting standing position and the trumpet performance posture , but a \n significant increase was noted in the marching euphonium performance posture compared with \n the resting standing position .\nthe lumbar paraspinal muscles are antigravity muscles which \n are contracted continuously while standing , thus easily incurring mechanical stress .\nit is \n conceivable that , since the muscle activity of the lumbar paraspinal muscles increases \n during the marching euphonium performance posture , holding the performance posture for a \n long time increases the load on the lumbar paraspinal muscles and is therefore a factor \n leading to lumbar fatigue and low back pain .\nthe muscle activity of the upper fibers of the \n trapezius increases in line with instrument weight in the trumpet to marching euphonium \n postures .\nwhen holding these instruments , the shoulder joint flexes and abducts , while the \n scapula rotates up and elevates .\nthe muscle activity of the upper fibers of the trapezius is \n likely to increase to maintain such a posture .\nwe also found that muscle activity of the \n cervical paraspinal muscles increased significantly in the euphonium performance posture \n compared with the resting standing position . since the posterior tilt angle of the trunk \n increases in the marching euphonium performance posture , it is necessary to tuck in the chin \n to face forward\nchin - in posture and is \n considered a posture in which the muscle activity in the cervical area including the \n cervical paraspinal muscles increases6 . \n sustained contraction of these muscles is a likely factor of muscle fatigue .\nfurthermore , \n obstruction of blood flow by sustained muscle contraction will result in myalgia7 .\ntherefore , holding the trumpet and marching \n euphonium performance postures for a long time would be factors of myalgia .\nthe present findings suggest that the trumpet and marching euphonium performance postures \n increase the load on the cervical and trunk musculoskeletal system .\nmoreover , the load on \n the musculoskeletal system increases in line with increased instrument weight .\nhowever , the \n trumpet and marching euphonium performance postures do not affect the musculoskeletal system \n of the lower limbs .\ntherefore , we consider it important to evaluate the cervical and trunk \n musculoskeletal systems and to conduct conditioning coaching appropriate for trumpet and \n marching euphonium performers .\nbecause these instruments are supported by the left hand and \n played with the right hand , the trunk and lower limb musculoskeletal system on the left \n side , that is , the supporting side , was measured in the present study .\nwe plan to measure \n the trunk and lower limb musculoskeletal system on the right side to elucidate the effect of \n performance postures on the whole body .\nin addition , it is possible that the trunk and lower \n limb musculoskeletal system is affected differently by the technique used to hold the \n instrument with the left hand during trumpet and the marching euphonium performance . because \n the angles and muscle activities of the upper arm were not measured in the present study , we \n plan to perform these measurements in a future study to elucidate the influence of different \n instrument holding techniques on the trunk and lower limb musculoskeletal systems .", "answer": "[ purpose ] the purpose of the present study was to investigate the effect of trumpet and \n marching euphonium performance posture on the trunk and lower limb musculoskeletal system . \n \n [ subjects ] the subjects were 10 female university students . [ methods ] subjects maintained \n a resting position , a trumpet performance posture , and a marching euphonium performance \n posture . the angles and muscle activities of the trunk and \n lower limbs were then measured . \n \n [ results ] the anterior tilt angle of the trunk decreased significantly in the trumpet and \n marching euphonium performance postures compared with the resting standing position , as \n well as in the marching euphonium performance posture compared with the trumpet \n performance posture . \n the muscle activity of the cervical paraspinal muscles , upper fibers \n of the trapezius , and lumbar paraspinal muscles increased significantly in the marching \n euphonium performance posture compared with the resting standing position , as well as in \n the marching euphonium performance posture compared with the trumpet performance posture . \n \n [ conclusion ] the results suggest that the performance position for trumpet and the \n marching euphonium performance increases the load on the cervical and thoracic \n musculoskeletal system , which increases with greater instrument weight . \n however , the same \n instrument performance postures had no affect on the musculoskeletal system of the lower \n limbs .", "id": 864} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrisperidone has been reported to be effective in management of disruptive behaviors , including hyperactivity , irritability , aggression , and temper tantrums . increased appetite , weight gain , headache , and sedation\nliterature search revealed only four published reports of risperidone - related bleeding , including hemorrhagic cystitis,1 ) nasal bleeding,2,3 ) and gastrointestinal bleeding.4 ) we hereby describe the first pediatric case of gingival bleeding during risperidone treatment .\nan 11-year - old - girl was referred to our out - patient clinic for her hyperactivity , temper tantrums , sleep problems , and self - injurious behaviors . according to her psychiatric assessment and psychometric evaluation ,\nshe was started on risperidone 0.25 mg / day treatment for her disruptive behaviors and two weeks later the dose was increased to 0.5 mg / day .\none - week after the dose increase , she experienced gingival bleeding when she brushed her teeth .\nrisperidone was considered to be the reason for bleeding , therefore we decided to reduce the dose to 0.25 mg / day .\ngingival bleeding ceased within a week . because worsening of her behavioral problems , her mother increased the dose to 0.33 mg / day .\nshe experienced gingival bleeding rarely ( twice a month ) and mildly during this dose regime , therefore we stopped the medication .\nwe decided to change risperidone to methylphenidate ; however , her parents refused to continue to the treatment because of their worries about the potential side effects .\nshe had no history of any bleeding disorder or any other medical condition including current allergies .\nshe was not taking any other medication other than risperidone at the time of the development of bleeding .\nthere are several case reports about risperidone - related bleeding ; however , to our knowledge , there is no report of gingival bleeding associated with risperidone in the literature .\nwe presented a case who experienced gingival bleeding when risperidone dose was increased to 0.5 mg / day , and subsided after decreasing the dose to 0.25 mg / day , suggesting a dose - dependent side - effect .\nhowever , the chronological relationship between the time of risperidone 0.5 mg / day administration and emergence of bleeding in the absence of an identifiable medical condition suggests risperidone to be the causative agent .\nthere was no other agent likely to be the cause of bleeding , except risperidone , and bleeding ceased when the dose was decreased .\nalthough an etiological relationship between risperidone use and gingival bleeding can not be drawn from a single case , the naranjo probability scale score ( 8) reveals a probable relationship.5 ) the bleeding side effect of risperidone might be caused by several mechanisms , including thrombocytopenia and 5-hydroxytryptamine 2a ( 5-ht2a ) receptor antagonism.3 ) thrombocytopenia is a known adverse effect of atypical antipsychotics and has also been reported during risperidone.6 ) in our reported case platelet count was normal , therefore , gingival bleeding could not be a consequence of thrombocytopenia .\nantagonism of 5-ht2a receptor was suggested to cause bleeding by inhibiting the release of vasoconstrictors from platelets and reducing the platelet aggregation.4 ) therefore , we may speculate that risperidone s high affinity to 5-ht2a receptors might have probably resulted gingival bleeding .\nthis case suggests that bleeding associated with risperidone may be a dose - dependent side effect .\nhowever , these potential explanations may not describe the entire mechanism of this adverse reaction .\nit is also possible that she might have some undetermined predisposing factors for bleeding that is triggered by risperidone .\nthere are several reports on gingival bleeding during anti - depressants;7 ) however , this is the first case on gingival bleeding associated with risperidone . although bleeding is a rare side effect , clinicians should be aware that risperidone may cause bleeding .\nrisperidone may also increase the risk of bleeding in susceptible patients with a history of coagulation disorders , and with concomitant use of other drugs , including non - steroidal anti - inflammatory drugs , aspirin , or other medications that affect coagulation .", "answer": "there are several case reports on risperidone - related bleeding ; however , to our knowledge , there is no report about gingival bleeding associated with risperidone in the literature . \n we presented a case who experienced gingival bleeding when risperidone dose was increased to 0.5 mg / day , and subsided after decreasing the dose to 0.25 mg / day , suggesting a dose - dependent side - effect . \n the bleeding side effect of risperidone might be caused by several mechanisms , including 5-hydroxytryptamine 2a receptor antagonism . \n although bleeding associated with risperidone is rarely reported , clinicians should be aware of this side effect .", "id": 865} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsensitive skin syndrome is a common and challenging condition , yet little is known about its underlying pathophysiology .\nsensitive skin is a common term used by patients and clinicians , as well as the cosmetic industry , and represents a complex clinical challenge faced by dermatologists and other skin care professionals .\npatients with sensitive skin often present with subjective complaints that are out of proportion to the objective clinical findings .\nthe patients complain of severe facial irritation , burning , and/or stinging after application of cosmetic products and toiletries such as sunscreens and soaps , yet they do not demonstrate the clinical stigmata of scaling , induration , and/or erythema that would be expected in known inflammatory or allergic processes .\nthe condition is often worsened by specific climatic conditions and may affect areas other than the face .\nmaibach described the cosmetic intolerance syndrome ( cis ) , which probably covers the bulk of the clinical presentation of the sensitive skin syndrome ( sss ) .\nfisher is credited with coining the term status cosmeticus to describe one extreme of the natural history of the cis in which the patient gradually becomes completely intolerant to the application of any cosmetic product .\nfundamentally , sss is a state of hyperreactivity to environmental stimuli , presenting with a clear clinical picture and resulting from a single underlying pathology or a combination of pathologies .\ndefined as a self - diagnosed condition , sss is by definition difficult to quantify .\nsome of the contradictions between investigators could be explained by flawed methodologies since the scientific community has yet to identify an acceptable objective screening test for sensitive skin .\nhowever , it is not only the subjective nature of the complaints that make sss difficult to diagnose .\nrobinson , by performing patch testing with sodium dodecyl sulfate ( sds ) and looking for intra - individual response patterns , found that there is significant positive correlation between sds and other irritants but noted overall low correlation coefficients .\nhe therefore deduced that it is inappropriate to define a subject 's reaction to a chemical based on his or her response to another irritant .\nshe skin - tested 58 subjects with history of strong positive sds or lactic acid response .\nsds- or lactic acid - positive group , a reaction to one irritant could not predict a reaction with another . to further complicate matters\nthere is evidence to suggest that no correlation exists between the lactic acid stinging test and the response to sds .\nthis data resonate the idea that even the reference irritants commonly used in studies of this topic do not correlate with each other and with hyperreactivity tendencies .\nfinally , judge tested 22 nonatopic adults with varying doses of sds and found marked inter - individual variation in the response threshold .\nthis complexityreinforces the need for a thorough diagnostic algorithm and , specifically , the need to test patients with multiple , repeated and complete ( i.e. all cosmetics applied by the patient at home ) patch testing before making a diagnosis .\nin order to formulate a systematic clinical approach , the medical and cosmetic communities have attempted to characterize the condition .\nlacking an objective screening test , investigators resorted to epidemiological studies using patient surveys . in a large epidemiological study in the uk (\nn = 2316 ) , a staggering 51.4% of women and 38.2% of men self - reported themselves as having sensitive skin . of note ,\ninterestingly , atopy did not appear to predict self - perceived sensitivity in the participating women .\nin addition , in the same study self - reports of sss symptoms were statistically over - represented in the self - reported sensitive cohort compared to the self - reported nonsensitive cohort .\nthis finding validates the link between self - perception of sensitive skin and neurosensory discomfort .\ntwo recent studies in the us and europe made similar observations . in the us ,\nfemales were significantly more concerned about sensitive skin than men ; however , no age or ethnic differences were found .\nthe european study reported an overall sensitive skin prevalence of 38.4% and found no ethnic differences .\nthe european study , once again , demonstrated that people who reported having sensitive skin were significantly more likely to experience sss symptoms . of note ,\nboth the american and european studies used large samples ( n = 994 and n = 4506 , respectively ) ; however , they were both limited by a phone survey methodology and the lack of any objective assessment . in light of the increased incidence of self - reported hypersensitivity in females ,\nhe compared the patch test responses of 384 patients to sds as the positive control and found increased reactivity in males compared to females .\nlammintausta tested seven males and seven females with sodium lauryl sulfate ( sls ) and then performed visual inspections , transepidermal water loss measurements , and dielectric water content measurements but like other investigators found no reactivity differences between males and females , adding to the overall controversy .\nfemale self - perception of sensitivity is consistently increased compared to that of males , yet when put through objective reactivity testing the trend is unclear .\nethnic differences in skin reactivity have been explored through the years , leading to the clinical hypothesis that black skin is less reactive than caucasian skin , which is in turn less reactive than asian skin . however , an epidemiological telephone survey performed in the us ( n = 811 ) revealed similar incidence of self - reported sensitive skin across four major ethnic groups ( afro - americans , asians , euro- american , and hispanics ) . the incidence rate of 52% is comparable to the incidence found in the uk ( see above ) .\nthe investigators did , however , find minimally statistically significant ethnic differences in the self - reported triggers and symptoms of sensitivity : afro - americans reacted less to environmental and alcoholic triggers ; hispanics reacted less to alcohol ; asians reacted more to wind , spices , and alcohol ; and euro - american reacted more to wind . in terms of symptomology , statistically significant increase in recurrent itching on the face was noted in the asian population , and fewer euro - american avoided certain cosmetics due to skin reactivity .\nthese findings were supported in a critical literature review , which showed that the evidence supporting the ethnic difference hypothesis using objective tests rarely reaches statistical significance and is often biased by subjective endpoints .\nrecent data looking into age - related differences in hyperreactivity are showing more consistent results .\nwhorl performed patch testing with 34 irritants on 2776 patients and found that young patients were more reactive than old patients .\nrobinson 's findings also corroboratedthe trend towards increased reactivity in the young subjects compared to the old subjects .\nthe mechanism leading to the sss has been debated in the literature , but the leading hypothesis relates to increased stratum corneum permeability .\nthere is a known inverse relationship between corneocyte size and stratum corneum thickness and the permeability of the skin , and changes in this mechanical barrier result in abnormal skin penetration by irritants .\nin addition , low levels of ceramides in the stratum corneum have been linked to increased severity of sls - induced irritant contact dermatitis , pointing toward barrier compromise in sensitive skin .\nseidenari linked self - reported hyperreactivity to decreased skin capacitance ( indicating decreased water content ) , objectively suggesting increased absorption of irritants by the sensitive - skin population . in the same study ,\nincreased erythema was objectively measured in hyperreacting subjects suggesting involvement of some baseline vascular component , and leading more recent investigators to propose the involvement of cutaneus sensory innervation in the pathogenesis of sss .\nas with many syndromes , the management scheme presented here emphasizes the diagnostic framework [ table 1 ] .\nthe clinical approach to the sss demands a thorough process of eliminating obvious as well as more subtle diagnoses .\nonce the diagnosis is made , deriving the appropriate treatment becomes a relatively simple task .\nnote that since much of the mechanisms of sss are unknown , the clinician must be comfortable with a certain degree of ambiguity and uncertainty . underlying mechanisms of sensitive skin syndrome it is reasonable to organize the differential diagnosis by dividing sss into visible and invisible sss .\nsome dermatoses that most clinicians find simple to diagnose may have atypical presentation and as a result lack the expected morphology .\neczema , atopic dermatitis , and rosacea are likely the three most common causes of sss related to barrier defect .\nfull discussion of these conditions is beyond the scope of this overview but we will highlight some common clinical features .\ncareful history , including family history and occupational history , combined with a detailed physical exam will often reveal the diagnosis . in the history\nparticular consideration should be given to culprits such as the masking effect of other topical agents applied by the patient .\nthe physical exam should include scrutiny of the face and scalp for subtle signs of minor inflammation , which are often masked in sss with underlying endogenous dermatoses . in all of these conditions\nthe patients are likely over - exfoliating their skin and thus exacerbating the barrier dysfunction . therefore ,\nfollowing specific treatment to halt the acute pathological process , preventing recurrence with a proper skin care regimen is indicated . in eczema and atopic dermatitis , the careful clinician may resort to short - term ( 2-week ) use of corticosteroids to stop the inflammatory process .\ncalcineurin inhibitors are alternatively indicated for delicate areas on the face . in an effort to control histamine release in atopic dermatitis\n, antihistamines can be added and a relatively allergen - free environment should be created . in rosacea , the mainstay of treatment is oral and topical antibiotics . in seborrhoeic dermatitis , azoles are the mainstay of treatment and low potency corticosteroids and emollients can be added acutely to treat the inflammatory process .\ncontact dermatitis ( cd ) and photocontact dermatitis ( pcd ) , as well as nonimmune contact urticaria ( nicu ) and immune contact urticaria ( icu ) , are all conditions that may elicit sss symptomology , with transient objective findings on physical exam .\nallergen - free products are now available and should be included as part of further skin care regimen in these patients .\nthe main reason why nicu is often a missed diagnosis in patients presenting with the sss is the transient nature of the reaction .\nthus , after testing with small amounts of product on the skin , the patient should be carefully examined using minimal magnification : the lesions will be typically revealed within 20 minutes .\ncommon trigger agents are fragrances ( e.g. cinnamic aldehyde ) and preservatives such as sorbic and benzoic acids . once triggers\nicu can be demonstrated with open and occluded testing , followed by prick testing with appropriate positive and negative controls if no response is elicited .\nvarious foods , latex , parabens , and other chemicals have been implicated in the causation of icu .\nhowever , there are cases in which no clinical clue is provided by the physical exam . in these cases , a 2-week trial of appropriate - strength corticosteroid may solve the mystery by pointing to an eczematous process in the case of symptoms resolution .\nnonetheless , the careful clinician should consider avoiding prolonged use of topical corticosteroids since there is anecdotal clinical experience of topical corticosteroids inducing sss and , at least in the case of barrier dysfunction , earlier and complete steroid tachyphylaxis has been demonstrated .\nif no symptomatic relief is observed , the patient 's sss is likely due to an invisible underlying cause .\nboth of these cases defined by maibach , no signs are present or can be elicited on the skin . in objective irritation\nthe mechanism is unknown and this diagnosis likely bundles more than one pathological process in it . interestingly ( and clinically frustratingly ) , maibach considers subjective irritation to be the most common cause of cis .\nfinally , body dysmorphic disorder ( bdd ) should always be considered by the dermatologist when assessing skin complaints without objective findings .\na recent cross - sectional study found a prevalence of 14% among patients in a cosmetic dermatology clinic . in the context of sss\n, dermatologists should be aware that facial irritation complaints without any findings on exam are a common presentation in the dysmorphic patients and therefore extra caution is warranted .\nreferral to a mental health professional is indicated since these patients are at risk of suicidal behavior .\nmaibach notes that patients suspected of having bdd often require a detailed diagnostic process in order to build the trust needed to safely refer them to the mental health professional . table 2 summarizes the steps in the evaluation of a patient suspected to have sss .\nspecific algorithms have been developed for the management of sss but they are the result of accumulated clinical experience and lack experimental evidence to support their use . nonetheless , algorithmic thinking may aid in ensuring complete assessment .\nthese algorithms include four basic steps : discontinuation , assessment , testing , and slow re - introduction .\ndiscontinuation of all topical medication and/or products , as well as elimination of activities and clothing resulting in skin friction , should be initiated and may need to last up to 12 months . the patient should then be assessed ( as described above ) for the occurrence of any visible dermatoses . if no clear pathology has emerged , rigorous testing is the next step .\ntesting should include patch and photopatch testing of routine allergens as well as of all of the patient 's skin care items .\nspecific testing for contact urticaria should be a part of the testing protocol . finally ,\nthe next step in management is slow re - introduction of the minimally necessary skin care products . for females ,\nrecommend adding low - allergenic- potential cosmetic products one at a time in the following order : lipstick , face powder , and blush .\nfor all products re- introduced , recommend testing by applying the product to a 2-cm area lateral to the eye for five consecutive nights and documenting the positive and/or negative result .\nthis exhausting process is not only a rational solution from a clinical management standpoint but may also aid in diagnosing the specific culprit in cases of invisible sss .\nunderstanding the underlying mechanisms may lead to the development of a well - standardized screening test .\nthis will allow clinical studies to rely on objective findings rather than self - reports and this , in turn , may result in more comprehensive and efficient management strategies .\nfemale self - perception of sensitivity is consistently increased compared to that of males , yet when put through objective reactivity testing the trend is unclear .\nit is reasonable to organize the differential diagnosis by dividing sss into visible and invisible sss .", "answer": "sensitive skin syndrome ( sss ) is a common and challenging condition , yet little is known about its underlying pathophysiology . \n patients with sss often present with subjective complaints of severe facial irritation , burning , and/or stinging after application of cosmetic products . \n these complaints are out of proportion to the objective clinical findings . defined as a self - diagnosed condition lacking any specific objective findings \n , sss is by definition difficult to quantify and , therefore , the scientific community has yet to identify an acceptable objective screening test . in this overview \n we review recent epidemiological studies , present current thinking on the pathophysiology leading to sss , discuss the challenges sss presents , and recommend a commonsense approach to management .", "id": 866} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlaparoscopic cholecystectomy with three or four ports is the standard operation for gallbladder diseases worldwide .\nthe established use of 5 or 10 mm instruments and ports leads to small skin incisions in the upper abdominal wall .\nhowever , these scars are still visible and might be a potential risk factor for incisional hernia or adhesions .\nfurthermore , new innovative methods such as notes ( natural orifice transluminal endoscopic surgery ) show promising first results regarding the technical feasibility and the possibility of scarless and painless operation [ 14 ] . at the present time\n, it becomes more important for younger patients to undergo surgery with none or at least very small scars .\nnotes surgery might be the solution but is in case of transvaginal access to the abdominal cavity limited to female patients , and the procedure is not as easy to learn .\nin addition , this technique requires special instruments , which do not exist in a regular department of surgery .\nbut due to the discussion about notes , another approach for the treatment of both genders is getting more attention from the public .\nthe transumbilical access , described in the literature amongst others as laparoscopic single - site surgery ( less ) [ 5 , 6 ] . for this technique ,\na 15 to 20 mm incision is made direct through the umbilicus , which is defined as a natural embryonic scare , and , therefore , the procedure is also called e - notes ( embryonic natural orifice transumbilical endoscopic surgery ) . beside the positive cosmetic effect of transumbilical incision , less incisional\nthis report describes our experience with single - incision cholecystectomies in 220 patients as standard procedure using a commercial available single - incision and conventional straight instruments .\nas far as we know , this is the largest series about single - incision surgery as standard procedure .\nbetween september 2008 and march 2010 , 220 laparoscopic single - incision cholecystectomies were performed at the vivantes klinikum am urban , berlin , germany by three experienced surgeons in standard technique .\nsingle - incision operation using two 5 mm and one 10 mm trocar was performed in 24 patients ( 11% ) between october 2008 and january 2009 .\npatients with symptomatic acute and chronic gallbladder disease were included in the observation , and all operations were performed consecutively .\nexclusion criteria for single - incision surgery were patients with gallbladder perforation , diagnosed in ultrasound or ct scan , with peritonitis or severe critical illness . all patients were hospitalized for at least two days and were completely informed about the single - incision technique .\nboth arms are rolled out and the monitor is placed on the opposite site of the surgeons near the right shoulder . the operation begins with a longitudinal incision direct through the umbilicus between both umbilical edges ( approximately 1.5 to 2 cm ) . for a clear and safe closure of the linea alba at the end of the operation , the umbilicus has to be disconnected from the ground with a scissor .\nafter good exposure of the linea alba with small hooks , the fascia has to cut with a scissor at a length of 15 to 20 mm . after dissolving of eventually existing adhesions with fingers ,\na langenbeck`s hook has to retract the inferior part of the incision and the single - port ( triport , olympus , germany ) can be safely brought into the abdominal cavity with the triport injector introducer . after establishing the pneumoperitoneum up to 14 \nmm hg with co , a 30 5 or 10 mm laparoscope was used for initial inspection of the abdominal cavity at a 1520 reverse trendelenburg , right - side - up position .\nwe used as instruments conventional straight 5 mm graspers and a 5 mm hook electrocautery device .\nbecause of the gel valves , a continuous grease of the instruments ( instellagel , farco - pharma gmbh , germany ) is important for a safe , nonfitful handling .\na special technique for a better movement inside the abdominal cavity is cross - handedness of the instruments .\nthat means to undercross the instrument in the left hand under the instrument in the right hand . for a right hander\nthe right hand holds the gallbladder with a grasper , and the hilum was prepared with a hook electrocautery device to expose the cystic duct and cystic artery .\nboth structures were clipped with a 5 mm endoscopic clip applier ( ligamax m / l , ethicon endo - surgery , oh , usa ) and divided with scissors .\nafter dissection the gallbladder from the fossa , the bladder was removed through the triport system without an endobag ( figure 1 ) .\nthe fascial incision was closed with a nonabsorbable 0 suture ( prolene , ethicon , germany ) .\nfinally , skin closure was done with an absorbable 4/0 suture ( monocryl , ethicon , germany ) .\ncomparison of the umbilicus before ( figure 2(a ) ) transumbilical incision and at the end of the operation ( figure 2(b ) ) demonstrates that the incision is only at the ground of the umbilicus .\nthe mean age of 142 females ( 65% ) and 78 males ( 35% ) was 47 years ( range : 1589 ) , and an elective surgery was planned for 154 patients ( 70% ) .\nthe average american society of anesthesiologists ( asa ) classification was 2 ( range : 13 ) and the body mass index ( bmi ) 28 ( range : 1549 ) . mean hospital stay was 4 days ( range : 220 ) and 103 patients ( 47% ) had secondary diagnoses .\nthirty - seven patients ( 17% ) presented preoperative bile duct stones and of all received an endoscopic retrograde cholangiography ( erc ) .\ntwenty - three patients ( 10% ) had clinical signs of biliary pancreatitis in medical history .\npreoperatively measured laboratory values were in a regular range for leucocytes , c - reactive protein ( crp ) , aspartate aminotransferase ( ast ) , alkaline phosphatase ( ap ) , and bilirubin .\nall patients received the same prophylactic antibiotic treatment of 2 g cefotaxim and 0.5 g metronidazol as single - shot dosage .\nmean operation time was 62 ( range : 26174 ) minutes , and 31 patients ( 14% ) had an incidential umbilical hernia .\ntwenty - two patients ( 10% ) had previously undergone abdominal operation , and 54 patients ( 24% ) showed peritoneal adhesions .\nthree patients ( 2% ) required conversion to a three - port technique because of a very large gallbladder with deep positioned hilus .\nan exact identification of the structures in the hilum via single port was not possible .\none patient had a severe bleeding out of the cystic artery after the first clip was accidentally removed .\na wound drainage was positioned at the end of operation in five cases ( 3% ) .\none patient developed a 2 cm necrosis of the bile duct after mirizzi 's syndrome , two days after the initial operation .\nof 220 patients , 202 ( 92% ) had gallbladder stones and 150 patients ( 68% ) multiple stones .\nsigns of gallbladder inflammation was diagnosed in 218 patients ( 99% ) , and 57 ( 26% ) patients had an acute cholecystitis .\nthe classification of inflammation grade was in 74 patients ( 34% ) light , 101 patients ( 46% ) moderate and 45 patients ( 20% ) severe .\na gallbladder hydrops was noted in 53 patients ( 24% ) , and ten patients ( 4.5% ) developed a shrunked gallbladder .\nwe could demonstrate in one of the largest series that single - incision cholecystectomy is feasible and safe as standard technique for elective and acute gallbladder disease .\nmost patients in our collective were satisfied with an almost scarless procedure and less pain after operation .\npreviously published studies about multiport technique which included more than 1000 patients showed similar results compared to our study group [ 911 ] .\nthe conversion rate to an open procedure was in former studies between 2% and 7% and in our population only 1% .\nmajor complications in multiport surgery such as bile duct or vessel injury were noted in 0.9% to 5.8% of all patients . although we had a comparative high complication rate of 5% , major complications like bile duct injury and necrosis happened only in two patients ( 1% ) , which is within the international standard .\nwhile single - incision surgery is getting more and more popular , patient numbers of previously published reports are still low [ 1219 ] .\na review of eight studies from 2009 about single - incision cholecystectomy shows only two studies with 100 patients [ 14 , 17 ] , and the largest series of single - incision surgery , published by lee et al .\none of the most important points in the discussion about notes or single - incision surgery is the extended operation time , because of a more complicated access to the abdominal cavity and the difficult handling of the instruments .\nthe mean operation time in eight studies about less surgery including 365 patients was 80 minutes ( range : 5194 ) [ 1219 ] .\nbut it is mentionable that studies with a higher case number like rivas et al . and\none reason might be that the learning curve for this technique is certainly longer as for the three- or four - port technique .\nrivas et al . compared in their study including 100 patients the first 50 patients with the second 50 ones .\nage and bmi were almost equal , but the operation time was considerable reduced from 73 to 45 minutes .\nour mean operation time was 64 minutes , and it is still close to the regular time for conventional laparoscopic cholecystectomy .\nhowever , we had a high percentage of patients with acute cholecystitis compared to other studies with 5% and 9% [ 14 , 15 ] .\na partition of our 220 cases into patients with acute and chronic cholecystitis showed a considerably different operation time .\nfifty - seven patients with acute cholecystitis required a mean operation time of 80 minutes ( range : 34174 ) and in contrast patients with chronic cholecystitis or no inflammation only 57 minutes ( range : 28159 ) .\nin addition , we could not indicate a reduction of operation time between the first 50% of operations and the second 50% like rivas et al .\nwe performed the operation in the first 110 patients in a median time of 61 minutes and the second 110 patients in a median time of 65 minutes .\nit seems that the learning curve has an important impact but is for an experienced laparoscopic surgeon not as important in large series .\nbut one reason for the more extended time in later operations might be the different view on the indication for single - port surgery after a major experience .\nthe first 30 patients had not undergone previously abdominal surgery and , therefore , the operation easier to perform with a reduced operation time .\nanother important point of criticism about single - incision surgery is the conversion rate to multiple ports .\nseveral studies reported about a conversion rate between 0% and 5% and are similar to our results with 2% [ 1316 , 18 , 19 ] .\nonly one study of lee et al . had a high conversion rate of 13.5% because of technical difficulties .\nconversion rate to an open procedure was 1% in our study group and is described in the literature with 0% to 2% [ 1316 , 18 , 19 ] .\nwe had to convert to an open procedure because of an acute bleeding from the cystic artery without an identifiable vessel in the hepatoduodenal ligament .\na blind closure of the vessel with 5 mm clips or bipolar thermocoagulation could have injured structures in the ligament .\nthe second patient had an unknown cholecystoduodenal fistula , which could not be closed in laparoscopic technique .\nconsidering these results , the conversion rate in single - incision surgery is even to multiport standard .\na view on the complication rates after single - site surgery in the literature shows a percentage between 0% and 5,4% [ 1219 ] .\nfour studies reported about no complications in their study population [ 13 , 14 , 18 , 19 ] . in our study , eight patients ( 5% ) developed postoperative complication , and six of these patients ( 3.5% ) had to undergo reoperation . except romanelli et al . , who had one case of postoperative hernia , other reports did not mention a reoperation .\nan analysis of our six patients showed that one of two patients with an incisional hernia had an incidential umbilical hernia and might have used a mesh for optimal wound closure .\ntwo patients developed a wound infection , and a wound debridement had to be performed in both cases .\nin one patient , the gallbladder was opened for extracting the stone and that might be the reason for infection .\nif the use of an endobag is more safely for preventing wound infection is questionable .\nwe did not use one endobag in our series and had only an infection rate of 1% .\nthese infections would have healed secondary , but because of a good cosmetic result , we decided to reoperate the patient .\nthese hernias could be safely repaired within the standard closure of the fascia using a nonabsorbable suture . in conclusion\n, we could demonstrate for the first time that laparoscopic single - incision cholecystectomy as standard procedure is feasible and safe compared to conventional multiport technique .\nbeside scarless operation , one major advantage in comparison to notes is the treatment option for both genders and the use of conventional instruments .\nresults of long - term followup have to answer the theoretical increased risk of incisional hernia .", "answer": "background and aims . \n we describe our experience of performing transumbilical single - incision laparoendoscopic cholecystectomy as standard procedure for acute and chronic gallbladder diseases . methods . between september 2008 and march 2010 , 220 patients underwent laparoscopic single - incision surgery . a single port was used for 196 patients and two conventional 5 mm and one 10 mm port in 24 cases . \n all operations were performed with straight instruments . \n results . \n single - incision surgery was successfully performed in 215 patients ( 98% ) . \n three patients ( 1.4% ) required conversion to a three - port technique and two patients ( 0.9% ) to an open procedure . \n average age of 142 women ( 65% ) and 78 men ( 35% ) was 47 years ( range : 1589 ) , average asa status 2 ( range : 13 ) and bmi 28 ( range : 1549 ) . \n mean operative time was 62 minutes ( range : 26174 ) and 57 patients ( 26% ) had histopathological signs of acute cholecystitis . \n eleven patients ( 5% ) developed to surgery - related complications and nine ( 4% ) of these required a reoperation . \n the mean followup was 331.5 ( range : 11590 ) days . \n conclusion . \n transumbilical single - incision cholecystectomy is a feasible and safe new approach for routine cholecystectomy . after a short learning curve , operation time and complication rate are comparable with standard multiport operation . \n in addition , most cases of acute cholecystitis can be performed with this technique .", "id": 867} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA Designed Functional Metalloenzyme that Reduces O2 to H2O with Over One Thousand Turnovers\n\nPaper sections:\n\nMuch progress has been made in designing metalloproteins with structures similar to native enzymes[1] and advances in computational biology have allowed for rational design of function as well[2]. Despite these achievements, most designed enzymes have simple active site structures and low activities with limited turnover numbers. Designing artificial enzymes with higher complexity and numbers of turnovers is not only an important measure of success in the field, but can also reveal structural features responsible for tuning enzymatic activities and may result in artificial enzymes for practical applications. A primary example of a complex metalloenzyme with an important function is the family of terminal oxidases, such as heme-copper oxidases (HCOs)[3] and bd oxygen reductases[4], which catalyze the kinetically difficult reduction of O2 to water and, in doing so, generate the transmembrane proton gradient that drives important processes such as ATP synthesis. While many catalysts that reduce oxygen to water have been reported[5], a long-standing challenge is to carry out the reaction without the production of reactive oxygen species (ROS), such as superoxide and peroxide, under mild conditions. ROS not only damage biomolecules in cells and components in fuel cells, but also decrease energy efficiency, as ROS are a result of incomplete catalysis. In addition, efficient catalysts using non-precious metal ions such as iron or copper will greatly decrease costs in practical applications[6]. Therefore, designing enzymes that catalyse complex reactions, such as oxygen reduction, at mild pH that are based on small, stable, and easy to produce scaffold proteins, would yield ideal models for studying the fundamentals of this chemistry and produce useful catalysts for applications such as fuel cells.
In HCOs the active site responsible for O2 reduction is a heterobinuclear metal center containing a heme-Fe and a His-ligated Cu (CuB). We have previously reported the introduction of two histidines in the heme pocket of sperm whale myoglobin (swMb) through Leu29His and Phe43His mutations[7], which, together with the native distal His64 formed a copper binding site (this mutant is called CuBMb, see Supporting Information, Figure S1A). As purified, CuBMb has no metal in the CuB site (designated as E-CuBMb; i.e. empty). Introducing the copper binding site into myoglobin transformed it from a simple oxygen carrier into a copper-dependent heme oxygenase at pH 8[8], which degrades the heme cofactor to verdoheme. Since the active site Tyr in native HCOs has been shown to be critical to the function of these enzymes[9], we hypothesized that the lack of a tyrosine next to one of the histidine ligands in copper loaded CuBMb (Cu-CuBMb) may limit conversion of O2 to water. Herein, we report the introduction of a Tyr at two different positions close to the histidines of the putative copper binding site of CuBMb and demonstrate that these artificial enzymes are able to efficiently reduce O2 to water, one with over 1000 turnovers, and with minimal release of superoxide or peroxide. These results demonstrate that both the presence and positioning of the tyrosine is important for terminal oxidase activity.
Since the design and activity of the CuBMb mutant were first reported[7\u20138], the crystal structure of E-CuBMb has been solved; the histidine ligands in this structure overlay well with those of bovine HCO (PDB 1V54) (see Supporting Information, Figure S1A) and this structure was used to guide the placement of Tyr in the active site pocket[11]. Since Tyr244 is four residues away from His240 in the primary sequence of bovine HCO, we first placed an analogous Tyr four residues from His29 via a Phe33Tyr mutation (called F33Y-CuBMb). The crystal structure of E-F33Y-CuBMb shows excellent agreement with the computer model (Figure S1B). A crystal structure of Cu-F33Y-CuBMb has also been obtained (Figures S1 and S2). However, although Tyr33 points into the Cu-binding site and is next to His29, Tyr33 does not overlay well with Tyr244 of bovine HCO (Figure 1A). To find a better structural overlay, a recent crystal structure of a cbb3 HCO[10] revealed that the Tyr can be near the His ligand spatially, while not necessarily close in the primary sequence. Therefore, we alternatively modelled Tyr next to His29 through a Gly65Tyr mutation (called G65Y-CuBMb). The energy-minimized computer model of E-G65Y-CuBMb overlays very well with that of cbb3 HCO (Figure 1B).
The spectral properties of oxidized and reduced states of these variants are similar to those of wild type swMb (WTswMb)[12] (Supporting Information, Figure S4). However, upon exposure of the ferric- states of both E-F33Y-CuBMb and E-G65Y-CuBMb to excess reductant (ascorbate with N,N,N\u2032,N\u2032-tetramethyl-p-phenylenediamine (TMPD) as a mediator) in air saturated buffer in a sealed cuvette, a transition from ferric through oxy to deoxy was observed (Supporting Information, Figure S4E\u2013F), which is in contrast to WTswMb (Supporting Information, Figure S4D), and prompted an investigation of the product of this reduction.
To confirm that the product of oxygen reduction is water, 17O NMR was carried out. Production of H217O above the background level (natural abundance) of H217O in water was monitored in a sealed vessel containing 17O2, the myoglobin variant, and excess reductant, using 17O-labeled Tyr as an external standard. A typical 17O NMR spectrum is shown in Supporting Information, Figure S5. Figure 2 shows the ratios of the H217O peak area to 17O-Tyr peak area at various time points after addition of 17O2 to initiate its reduction by WTswMb, E-F33Y-CuBMb, and E-G65Y-CuBMb, normalized to the area of the peak before initiating the reaction. The normalized ratio of water in the WTswMb sample remains close to 1, suggesting that the protein did not produce any new H217O. In contrast, E-F33Y-CuBMb and E-G65Y-CuBMb produced up to 10 mM H217O at 120 min, as indicated by an increase in the normalized ratio, confirming the production of water.
The rates of oxygen reduction were measured quantitatively using an O2 electrode to monitor the concentration of O2 over time in the presence of reductant, similar to protocols reported for native HCO[13]. The rate of O2 disappearance was measured for WTswMb and the CuBMb variants (Supporting Information, Figure S6). A hallmark of native terminal oxidases is the clean reduction of O2 to water with minimal release of superoxide or peroxide[14]. To identify the product (O2\u2212, O22\u2212, or H2O) we employed superoxide dismutase (SOD) and catalase which selectively react with superoxide and peroxide, respectively, producing O2 as one of the products, which would slow the apparent rate proportional to the amount of ROS released. By comparing the rates of reduction in the absence of and in the presence of SOD and catalase, the portion of O2 reduction due to water formation (in blue) and due to superoxide or peroxide formation (in red) can be calculated (see Figure 3A, and Supporting Information Table S5 and Supporting Text). Not surprisingly, most of the O2 consumption rate by WTswMb is due to superoxide or peroxide formation, consistent with autoxidation[15] and these rates remain unaffected in the presence of Cu2+, Zn2+ or Ag+. Interestingly, introducing two histidine residues into the distal pocket of WTswMb results in substantial inhibition of superoxide/peroxide formation in comparison to WTswMb, but does not significantly contribute to water formation, and therefore results in a decrease in the overall rate of O2 consumption. Similar to WTswMb, addition of Cu2+, Ag+ or Zn2+ to E-CuBMb does not perturb the rate and product of O2 reduction. In contrast to both WTswMb and CuBMb, introducing a Tyr next to the one of the His ligands at either position 33 or 65 results in a dramatic increase in water formation and overall rate of O2 consumption. The rate of water production increases up to 4.2 and 1.1 \u00b5M/s when using 18 \u00b5M E-G65Y-CuBMb and E-F33Y-CuBMb, respectively. To our knowledge, this is the first time that Tyr and its specific positioning has been shown to play an important role in directing the product of O2 reduction to water formation instead of release of superoxide or peroxide. Under further optimized conditions (with a higher concentration of reductant), the rate of O2 reduction to water by E-G65Y-CuBMb is 28 min-\u22121 (Supporting Information, Figure S10) \u2013 within ~150 fold of native HCOs[16]. Additionally, we show in Supporting Information, Figure S7 that 1.8 mM and 18 mM cyanide, a known inhibitor of HCO activity, inhibits the activity of E-G65Y-CuBMb and E-F33Y-CuBMb, respectively.
Surprisingly, the O2 reduction activity is independent of the presence and identity of the metal in the engineered CuB site (Figure 3A). To further support this finding, we repeated the studies with varying equivalents of copper (0\u20132 equivalent) as well as a strong metal chelator, ethylenediaminetetraacetate (EDTA), but no further change was noticed (Supporting Information, Figure S8). As E-G65Y-CuBMb is still ~150 fold lower in activity than HCOs,[16] our results are not intended to rule out the role of copper ion native HCOs. Alternatively, these results do indicate that a copper center is not strictly necessary for oxygen reductase chemistry and are consistent with recent discovery of bd oxygen reductases[4] that lack the CuB center and yet can still perform the oxidase activity.
More importantly, this study demonstrates the importance of the presence and positioning of tyrosine in the active site. In both types of native oxidases the reaction is either known or proposed to proceed by the critical steps of two electron reduction of the oxygen to a peroxo intermediate, followed by rapid protonation and heterolytic O-O bond cleavage, leading to a transient ferryl intermediate; it is also proposed that the conserved tyrosine in HCOs is involved in donating an electron.[3\u20134] To elucidate the potential role of the Tyr, we have obtained the crystal structure of E-F33Y-CuBMb. When comparing with E-CuBMb and E-F33Y-CuBMb with WTswMb, we found that introducing two histidine residues and then an additional tyrosine residue has led to stabilization of two and three water molecules, respectively, in the distal pocket (Supporting Information, Figure S11), in comparison to one water molecule in the distal pocket of WTswMb. In addition, where WTswMb has only one hydrogen bond partner available to interact with the bound oxygen (H64), two and three more hydrogen bonding capable residues are available in E-CuBMb and E-F33Y-CuBMb, respectively. Studies of crystal structures of various states of HCOs have suggested a role for water molecules and an extended hydrogen bonding network in the oxygen reduction step[17], and computational studies[18] of HCOs have supported the role of similar interactions in oxidase activity. Based on these studies, we propose that tyrosine and its associated hydrogen-bonding network works to activate the ferric-superoxo state of our designed enzymes and this activation allows it to accept a second electron from the exogenous reductant towards complete reduction to water. Further studies are underway to elucidate the exact role of Tyr in our model protein system.
Finally, to test the extent of the functional activities, we have carried out multiple turnover reactions. To a solution containing E-F33Y-CuBMb or E-G65Y-CuBMb and excess reductant, ~500 \u00b5M (28 equivalents) O2 was added repeatedly and each time the total O2 consumption was monitored using an O2 electrode. These stepwise additions resulted in the multiple plateaus observed in Figure 3B. We calculate that E-F33Y-CuBMb and E-G65Y-CuBMb achieved >505 and > 1056 turnovers, respectively (Figure 3B, inset).
In summary, we have demonstrated the first successful design of a functional protein capable of cleanly reducing oxygen to water with minimal release of superoxide or peroxide, similar to the activity of terminal oxidases, with more than 1000 turnovers. Through these designed functional proteins, we have also shown that Tyr next to one of the copper coordinating His ligands plays a critical role in directing O2 reduction to water formation. Furthermore, the positioning of this Tyr is critical for affecting the rate of catalysis. Even though the designed proteins are still less active than terminal oxidases, it is remarkable that oxygen reduction to water was conferred to a much smaller protein, myoglobin, with only three mutations of the distal pocket. Given their high enzymatic turnovers, smaller size, higher stability, and higher expression yield, these designed enzymes will serve as ideal models for a more detailed understanding of terminal oxidases and allow for potential applications in biology and alternative energy.
", "answer": "Summary Rational design of functional enzymes with high turnovers is a significant challenge, especially those with complex active site and difficult reactions, such as in respiratory oxidases. Introducing 2 His and 1 Tyr into myoglobin resulted in designed enzymes that reduce O2 to H2O with > 1000 turnovers and minimal release of reactive oxygen species. This also showed that presence and positioning of Tyr, not Cu, are critical for activity.", "id": 868} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nklippel - trenaunay syndrome ( kts ) is characterized by the triad of port wine stain , venous and lymphatic malformation , and soft tissue hypertrophy of the affected extremity .\ndepending on the type of vessel involved and its flow characteristics kts is classified as a slow flow complex combined capillary venous or capillary venous lymphatic malformation .\nthe localized variants are solitary angiokeratoma , fordyce 's angiokeratoma , angiokeratoma of mibelli and angiokeratoma circumscriptum naeviforme ( acn ) .\nthe systemic form , angiokeratoma corporis diffusum , is usually associated with an inborn error of metabolism . among all the types , acn is the rarer and the only congenital variant of angiokeratoma .\nthe lesions of acn are bluish red , well defined and are classically seen on the lower extremity in a unilateral distribution .\na 4-year - old male child presented with complaints of a linear eruption on his right leg since birth .\nhis parents gave history of pain and several episodes of bleeding from the lesion after trauma .\n, there were multiple hyperkeratotic discrete and closely aggregated papules and plaques of varying size on an erythematous base arranged linearly along the lateral aspect of the right thigh extending up to the knee joint [ figures 1 and 2 ] .\nright lower limb arteriovenous ( av ) doppler revealed a hypoplastic right lower limb deep venous system with compensatory dilatation of the superficial venous system .\nthe superficial femoral vein , popliteal vein , anterior tibial and posterior tibial vein on right side were hypoplastic along with thickening of subcutaneous tissue and associated dilatation and malformation of the superficial venous system [ figures 5 and 6 ] .\nhistological examination revealed numerous dilated thin walled , congested capillaries mainly in the papillary dermis and very few in reticular dermis .\noverlying epidermis showed compact hyperkeratosis , irregular acanthosis with elongated rete ridges consistent with diagnosis of angiokeratoma [ figures 7 and 8 ] . on the basis of clinical , histological and radiological findings\ndilated superficial venous system verrucous plaque with soft tissue hypertrophy prominent superficial veins on dorsum of foot plain radiograph showing soft tissue hypertrophy magnetic resonance imaging angiography showing dilated superficial veins on the right side dilated superficial venous system hyperkeratotic epidermis with congested capillaries in papillary dermis with normal deep dermis and subcutaneous tissue hyperkeratotic epidermis with dilated congested capillaries in papillary dermis\nin 1900 , two french physicians maurice klippel and paul trenaunay described two patients with hemangiomatous lesions of the skin with associated bone and soft tissue hypertrophy and coined the term naevus variqueux osteohypertrophique . in 1907 , parkes weber reported the association of kts with av fistula and called it hemangiectatic hypertrophy . in 1965\n, lindenauer proposed that the syndrome originally described by klippel and trenaunay without av malformation be considered as a specific entity the kts and the one associated with av fistula be designated as parkes weber syndrome . in a study of 252 patients with kts at the mayo clinic , 63% had all three features of kts .\nport wine stains were found in 98% of patients , venous malformations in 72% and limb hypertrophy in 67% patients .\nthe port wine stain is apparent at birth and usually involves the affected limb , often stopping at the midline with a sharp linear border .\nthe nevus may involve the whole of one side of the body and may sometimes be present on the contralateral limb .\nvaricose veins may be obvious at birth , but frequently become evident after walking starts .\nthe venous abnormalities of the deep venous system that occur in kts include aneurysmal dilatation , duplication , aplasia , and hypoplasia .\npatients with at least two of the three cardinal features have been classified as having an incomplete form of kts .\nit is the only congenital variant and is more common in women and is usually unassociated with systemic disease .\nthe histopathological finding is same irrespective of the type of angiokeratoma and consist of numerous thin walled congested capillaries mainly in the papillary dermis underlying an epidermis that shows variable degree of acanthosis with elongation of rete ridges and hyperkeratosis .\nunusual variants of acn described in literature are along the lines of blaschko , and a systematized band like pattern .\nverrucous hemangioma clinically resembles angiokeratoma but they can be differentiated histopathologically as the former involves the dermis and the subcutaneous fat and the latter involves only the dermis .\nour case showed typical clinical features of acn , which was confirmed by histopathologic examination .\nassociated soft tissue hypertrophy and deep venous malformation on mri are classical features of kts .\nthere are very few case reports of association of kts with acn in world literature .\nschimpf and wehberg in their study have reported three cases of acn on the lower limb associated with soft tissue hypertrophy .\nbone hypertrophy was present in two cases , varicose veins in one case and only one case had associated port wine stain on the back .\nthe case reported by odeh had acn of the right leg associated with soft tissue hypertrophy and bone hypoplasia of the right half of pelvis .\nthey preferred the term hemangiectatic hypertrophy as there was no associated bony and venous abnormalities of kts .\nto the best of our knowledge , this is the first case report of this rare association from india .", "answer": "klippel - trenaunay syndrome ( kts ) is a cutaneous capillary malformation on a limb in association with soft tissue swelling with or without bony hypertrophy and atypical varicosity . \n the capillary malformation associated with kts is port wine stain . \n angiokeratoma circumscriptum naeviforme ( acn ) is a congenital variant of angiokeratoma commonly present on the lower limb as a hyperkeratotic plaque . \n acn is rarely associated with kts . \n we report a case of acn with soft tissue hypertrophy and deep venous malformation ( possibly a variant of klippel - trenaunay ) in a 4-year - old male child .", "id": 869} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nImide arylation with aryl(TMP)iodonium tosylates\n\nPaper sections:\n\nThis article is part of the Thematic Series \"Hypervalent iodine chemistry in organic synthesis\".
\n\nIntroduction\nImides are important structural units in a range of approved pharmaceuticals and agrochemicals (Scheme 1a) [1]. Despite the general prevalence of imides, N-aryl imide derivatives are relatively rare in such compounds. We were surprised by this disparity, but found that a lack of methods to synthesize N-aryl imides may explain their scarcity; this is particularly true relative to other N-aryl compounds. The survey of methods revealed that the dominant approach to N-aryl imides is to employ aniline starting materials (Scheme 1b, left), as was done in the synthesis of pentoxazone and related herbicides [2]. The alternative aromatic substitution approach with imide anions (Scheme 1b, right) is hampered by their low nucleophilicity [3]. Therefore, transition metals feature prominently in such methods, but even recent examples employ stoichiometric metal mediators [4]. Metal-free methods by classic SNAr are also attractive, but only possible on very electron-deficient arene substrates [5]. Diaryliodonium salts are useful reagents for metal-free aryl transfer [6\u201310] and Mu\u00f1iz and co-workers have recently reported an elegant study on sterically controlled C\u2013N coupling of 2,6-disubstituted aryl(phenyl)iodonium salts and imides [11]. We have been investigating the generality of electronically controlled aryl transfer from aryl(trimethoxyphenyl)iodonium salts [12\u201314] and describe here the development of a C\u2013N coupling of a phthalimide anion with non-sterically biased aryl groups. The protocol is compatible with ortho-, meta-, and para-substitution on the aryl group and the phthalimide moiety may also provide access to anilines.
\n\n\nImides as an important scaffold.
\n\nResults and Discussion\nWe initiated our optimization of the arylation of the potassium phthalimide nucleophile with diaryliodonium electrophiles by surveying several reaction conditions: dummy ligand (Aux), counter anion, solvent and volume, reaction temperature, and stoichiometry (Table 1). Consistent with an electronically controlled aryl transfer, the trimethoxyphenyl (TMP) auxiliary was superior to mesityl (Mes), phenyl (Ph), and anisyl (An) auxiliaries under several different reaction conditions (Table 1, entries 1\u20133; 11 and 12; 16 and 17). While the counter anion did not exert a dramatic influence on the reaction yield, using tosylate (OTs) produced the highest yield in both DCE and toluene as solvent (Table 1, entries 4\u20138). Given our ability to readily access aryl(TMP)iodonium tosylate salts [12] we continued our optimization with these reagents. We observed a very narrow operating temperature with a maximum yield at 100 \u00b0C when toluene was used as solvent (Table 1, entries 9, 10, and 12). We also observed that the reaction yield decreases with dilution (Table 1, entries 13\u201315). Finally, the yield increases with increasing stoichiometry of phthalimide (Table 1, entries 10, 13, and 17). It is also important to note that under \"optimal\" conditions (Table 1, entry 17) we did not observe a Phth\u2013TMP adduct. Moreover, we did observe essentially quantitative formation of TMP\u2013I and therefore complete consumption of 1a and high fidelity for aryl transfer selectivity. At this time we are unable to account for the remaining mass balance (\u224825%) of the methyl benzoate moiety of 1a. We have employed the conditions of entry 17 (Table 1) as our standard conditions to evaluate the scope of this reaction.
\n\n\nDiscovery and optimization of reaction conditions.a
aConditions: 1 (0.1 mmol, 1 equiv), potassium phthalimide (see table for equivalents), solvent (see table), temperature (see table), 24 hours.
\n\nResults and Discussion\nWe have assessed the scope of compatible aryl groups under our optimal conditions (Scheme 2). Under electronic control, strong electron-withdrawing groups on the aryl ring lead to high yield of N-aryl phthalimide products (Scheme 2, 2a\u2013d, 66\u201390% yield). However, the TMP auxiliary also enables the coupling of phthalimide with moderately electron-deficient aryl groups. For instance the p-chlorophenyl moiety (2e) is coupled to phthalimide in moderate yield (42%). Additionally, we have observed that electronic and steric effects operate in concert to couple an o-tolyl (2f) moiety to phthalimide in high yield (67%). In this case, 2,6-disubstituted aryl groups are not required for a sterically controlled coupling. Finally, as an example two polysubstituted aryl groups are introduced in this coupling reaction, which are specifically enabled by the use of an unsymmetrical aryl(TMP)iodonium electrophile (Scheme 2, 2g and 2h, 42 and 99% yield, respectively).
\n\n\nScope of compatible aryl groups. Conditions: 1 (0.5 mmol, 1 equiv), potassium phthalimide (2.5 mmol, 5 equiv), toluene (2.5 mL), 100 \u00b0C, 24 hours. Isolated yields are reported.
\n\nResults and Discussion\nThe phthalimide moiety is well-recognized as an \"NH3\" surrogate, and the products depicted in Scheme 2 may be deprotected to yield aniline derivatives. In a specific example, 1a is reacted under modified conditions to yield 2a. In this one-pot procedure, hydrazine in aqueous ethanol is added directly to the reaction mixture and aniline 3 is isolated in 63% yield from 1a (Scheme 3).
\n\n\nOne-pot synthesis of anilines.
\n\nResults and Discussion\nWe have previously described the coupling of aryl(TMP)iodonium tosylates with azide nucleophiles [14]. Azide is a notably stronger nucleophile than phthalimide and it is interesting to compare the reaction of these two nucleophiles with 1a under similar conditions (Table 2). The Mayr nucleophilicity constant of azide [15] is 20.5 and high yield (95%) is observed in a reaction with 1a under relatively mild temperature (65 \u00b0C) and short reaction time (2 hours, Table 2, entry 1). The Mayr nucleophilicity constant for phthalimide is five-orders of magnitude lower (15.5) [3] and under similar conditions leads to trace product (Table 2, entry 2). In order to obtain a high yield of 2a, albeit lower than given in entry 1, a higher temperature (100 \u00b0C) and a longer reaction time (24 hours) are required (Table 2, entry 3). This suggests that the contribution of nucleophilicity (via Mayr nucleophilicity constants) [16] may be useful in developing other coupling reactions with diaryliodonium electrophiles.
\n\n\nComparison of nucleophilicity.
\n\nConclusion\nThe coupling of both electron-deficient and sterically encumbered aryl groups with a phthalimide anion is achievable with aryl(TMP)iodonium tosylate salts. This is an electronically controlled coupling reaction that is enabled by the TMP auxiliary and complementary to the sterically controlled coupling previously reported. We anticipate that this reaction will find use as a starting point for the synthesis of N-aryl imides in a range of applications.
\n\n\nGeneral experimental details, procedures, tabulated spectroscopic data, and 1H, 13C{1H}, and 19F NMR spectra of compounds 1g, 2a\u2013i, and 3.
", "answer": "Herein, we describe the synthesis of N-aryl phthalimides by metal-free coupling of potassium phthalimide with unsymmetrical aryl(TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electron-rich trimethoxyphenyl group acting as a competent dummy ligand. The yields of N-aryl phthalimides are moderate to high and the coupling reaction is compatible with electron-deficient and sterically encumbered aryl groups.", "id": 870} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nlung transplantation is an established therapeutic option for patients with advanced cystic fibrosis ( cf ) .\nthe success of the first transplant for a patient with cf in 1983 spurred further refinement of the management and selection criteria of patients , leading to significant survival benefit .\nhowever , patients with advanced cf present a unique microbiological challenge , with disease characterised by bronchiectasis , severe airflow obstruction , high bacterial loads , and recurrent lower respiratory tract infections [ 46 ] . unsurprisingly\n, some centres turn down patients on the basis of colonisation with multiresistant bacteria . the most common respiratory pathogen that colonises patients with cf is pseudomonas aeruginosa , with up to 80% of patients being culture - positive for this organism .\nas the presence of this microorganism has negative prognostic implications , it is disturbing to note that levels of resistance to frontline antipseudomonal agents are very high .\nthe presence of multi- and pan - resistant p. aeruginosa renders methods of single - agent antibiotic susceptibility testing suboptimal .\nthe conventional manner of managing patients who are colonised with these microorganisms is to empirically treat them with combinations of antibiotics in the peritransplant period .\nunfortunately , an empirical approach might lead to inadequate bactericidal levels and the prescription of antibiotics that antagonise each other .\nthis approach is undesirable , as patients with pan - resistant bacteria have shorter follow - up periods and decreased survival rates after transplant . \nan alternative approach is to utilise multiple combination bactericidal testing ( mcbt ) , a technique that had previously been used to systematically test bacterial isolates against multiple combinations of antibiotics to determine susceptibility patterns and identify optimal combinations for potential treatment .\nprevious studies have demonstrated that using combinations of antimicrobials may generate higher levels of in vitro bactericidal activity against p. aeruginosa and burkholderia cepacia complex . \nour centre currently advocates the use of mcbt ( with modified antimicrobial concentrations ) to determine appropriate prophylactic regimens in patients about to undergo lung transplantation for cf and other lung pathologies that are colonised with antibiotic - resistant gram - negative bacteria .\nto evaluate the effectiveness of our strategy , we undertook a retrospective analysis to compare the rates of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using the mcbt versus those who had their antibiotics chosen via conventional sensitivity testing .\nwe performed a retrospective analysis of all patients who underwent lung transplantation for cf between january 2000 and august 2010 .\npatients were included in the review if they were colonized pretransplant with p. aeruginosa ( as demonstrated by sequential sputum cultures ) and were excluded if they were colonized with b. cepacia complex .\ndata was collected from patients ' case notes and clinical charts ; looking specifically at incidences of septicaemia at 30 days , posttransplant wound infection at 30 days , empyema at 30 days , all - cause mortality at 30 days , and all - cause mortality at one year .\nthese were mapped against antibiotic resistance , method of sensitivity testing , and choice of antibiotics that were administered .\ninfections were defined by combining positive laboratory culture from tissue source ( blood , surgical wound , and pleural fluid ) with at least two of the following four parameters : tachycardia ( heart rate > 90 beats per minute),hypotension ( systolic blood pressure < 90 mmhg),body temperature < 36c or > 38c , abnormal inflammatory markers ( white cell count < 4 10 cells / l or > 12 10 cells / l , c - reactive protein > 10 mg / l ) . tachycardia ( heart rate > 90 beats per minute ) , hypotension ( systolic blood pressure < 90 mmhg ) , body temperature < 36c or > 38c , abnormal inflammatory markers ( white cell count < 4 10 cells / l or > 12 10 cells / l , c - reactive protein > 10 mg\nprophylactic antimicrobials were chosen based on disc susceptibility testing using british society for antimicrobial chemotherapy ( bsac ) breakpoints .\nif sputum was culture positive for pan - resistant p. aeruginosa or recent culture results were unavailable , patients were treated empirically with aztreonam , an antistaphylococcal agent ( either flucloxacillin or clindamycin ) , and metronidazole .\npatients who did not receive peritransplant antibiotics chosen via the mcbt method were deemed to have received antibiotics using conventional means .\nperioperative antibiotics were continued until the patient was extubated and could demonstrate a good cough , ( two - three days ) to a maximum of seven days .\nthis was used in conjunction with conventional means of choosing peritransplant antibiotics , but , since 2008 , mcbt became the default method for the determination of bactericidal agents for all patients colonised with antibiotic - resistant gram - negative nonfermenters .\nbactericidal activity was determined by testing at least 12 antimicrobials individually and in combination with each other , leading to 66 different combinations .\nseveral morphotypes of p. aeruginosa from at least two pretransplant sputa were selected for testing . \neach antimicrobial or combination of antimicrobials was tested in isosensitest broth using systemic breakpoint concentrations as specified by the bsac .\nafter 48 hours incubation at 37c , the turbidity of each broth was measured at 620 nm .\nbroths without detectable bacterial growth were subcultured onto blood agar to calculate 99.9% bacterial kill .\nperitransplant antibiotic regimens were then chosen based on mcbt results and patients ' allergy history . any other gram - negative species ( including nonfermenters and/or enterobacteriaceae ) that may have isolated alongside p. aeruginosa\nwere also tested using the mcbt , and antibiotic cocktails were chosen that showed bactericidal activity against such mixtures of species . \nour centre used a three - day induction protocol with antithymocyte globulin ( titrated by flow cytometric analysis of peripheral blood t lymphocytes ) and intravenous methylprednisolone at a dose of 2 mg / kg .\nalternatives were used in the context of an international clinical trial ( mycophenolate ) or in cases of ciclosporin intolerance ( tacrolimus was used ) .\nup to five days of intravenous ciclosporin was given in the context of poor ciclosporin absorption in patients with cf .\nbetween january 27 , 2000 and august 23 , 2010 , 163 lung transplants were performed on patients with cf .\nthis number included patients who were previously turned down by other centres on the basis of their microbiology .\na total of 129 patients were colonized with p. aeruginosa and not colonized with b. cepacia complex .\nfifty patients were given antibiotics that were chosen based on the mcbt , and there were 79 patients in the conventional group .\nour patients were colonized with strains of p. aeruginosa with varying degrees of antibiotic resistance .\nwe defined pan - resistance as resistance to antipseudomonal quinolones , -lactams , aminoglycosides , and colomycin . in this cohort\nthese organisms were resistant to all single agents tested but bactericidal combinations with colomycin and another agent were identified .\nseventy - one patients were colonised with multiresistant p. aeruginosa , and nine patients were colonised with fully susceptible strains .\nforty - seven patients were colonised with organisms that were resistant to one or two groups of antimicrobials . \n\nfigure 1 shows the relative rates of infectious complications after lung transplantation in both groups .\ntwo patients ( 4% ) who were given antibiotics based on mcbt developed septicaemia compared to 13 ( 16.5% ) in the conventional group ( p 0.05 ) .\nthe occurrence of gram - negative sepsis was statistically lower in the mcbt group , and p. aeruginosa was responsible for only one case of septicaemia compared with seven in the conventional therapy group ( see table 2 ) .\np. aeruginosa was recovered from the posttransplant pleural fluid of one patient ( 2% ) in the mcbt group , as opposed to six ( 7.6% ) in the conventional group ( p = 0.25 ) .\nthere were no statistically significant differences in the rates of surgical wound infection ( 6% in the mcbt group , 3.8% in the conventional group ) .\nthere were no statistically significant differences in all - cause mortality rate at 30 days , with a 10% mortality rate in the mcbt cohort and 6.33% in the conventional group .\nthis lack of statistical significance was replicated in all - cause mortality rate at one year ( 22% in the mcbt group , 19% in the conventional group ) .\nlung transplantation for cf accounts for approximately one - third of all single sequential lung transplants performed at our centre .\nthe complex microbiology involved in this cohort of patients may lead to anxiety when listing patients with multi- and pan - resistant p. aeruginosa , but this paper demonstrates for the first time that the mcbt may have a significant role in altering posttransplant infective complications for patients with cf .\nthe data indicates that whilst there may not be evidence for an effect on all - cause mortality , patients who had antibiotics chosen using mcbt had lower rates of morbidity .\nthe presence of pleural infection and septicaemia not only negatively impacts the patients ' transplant journey but prolongs the hospital length - of - stay and adds substantial economic burden . we had excluded patients who were colonised with b. cepacia complex for the purposes of this retrospective analysis .\nthis is due to the tendency of these patients to succumb to overwhelming sepsis with one - year mortality rates of between 50% and 100% [ 18 , 19 ] .\nour group had also previously noted that infection with burkholderia cenocepacia in particular led to even poorer mortality outcomes . unfortunately , we were unable to look at exact causes of death ( septicaemia in particular ) in our patient cohort as causes of death were not readily identifiable in all cases .\nthis is a reflection of the wide geographical referral area that is covered by our centre as well as the degree of shared care with referring centres ( covering the north of england , scotland , northern ireland , and the republic of ireland ) .\na previous analysis of all patients who underwent lung transplantation for cf at our centre had identified sepsis as the cause of death in 18 cases ( 26% of all recorded cf transplantation recipient deaths ) .\nb. cepacia complex was implicated in seven of these cases . in an additional three cases , clinical sepsis\nprospective studies would play an important role in determining if the use of mcbt can significantly decrease the rate of early mortality due to septicaemia . \naaron et al . had compared the efficacy of using antimicrobial combinations derived from mcbt with those derived from conventional susceptibility testing for treatment of acute pulmonary exacerbations of cf .\nthey concluded that regimens based on mcbt results did not result in a better clinical or bacteriological outcome .\nit is difficult to make comparisons between our findings and theirs for both clinical and technical reasons . on the clinical side , the patient populations ( post - lung - transplant cf versus non - lung - transplant cf ) and outcome measures were different .\nthere are also major differences in the antimicrobial concentrations used in our modified mcbt test and the test as originally described [ 13 , 14 ] . in our study ,\nsystemic breakpoint concentrations specified by the bsac to define susceptibility were used in a modified mcbt whereas antimicrobial concentrations in the original mcbt were chosen on the basis of published estimates of the average peak levels seen in serum after standard single - dose intravenous administration . as a result ,\nthe antimicrobial concentrations used in our modified mcbt were typically two- to eightfold lower than those previously described .\nas a consequence , fewer isolates would be likely to be classified as susceptible in our study . \nit is impossible to conclude whether the use of lower breakpoint concentrations of antimicrobials would have led to more favourable outcomes in the study of aaron et al . . \nas this is a retrospective study , we readily acknowledge that there are inherent limitations to our findings .\nthe ten - year period covered by the study has seen numerous changes with regards to developments in lung transplantation .\nthese include changes in immunosuppression regimen and the natural progression with regards to peritransplant management as the members of our centre gain more experience . given the nonrandomized nature of this study and temporal confounding factors , we can not definitely conclude that mcbt should be given at induction to all patients colonized with p. aeruginosa .\nhowever , the fact that we are dealing with a unique cohort of patients with significant microbiological challenges might render it unethical to conduct a full randomized control trial .\nfurthermore , it is unlikely that sufficient numbers are recruited to adequately power such a study .\nthe data presented is the first indication that patients given antibiotics based on mcbt results had significantly lower rates of septicaemia and lower rates of positive microbiological cultures in their pleural effusions .\nthis is an encouraging finding , lending credence to the need for multi - centre prospective studies to be performed that will ideally lead to no patients being turned down for a lung transplant on the basis of colonisation with resistant microorganisms .", "answer": "early infection is a recognised complication after lung transplantation in patients with cystic fibrosis ( cf ) . \n our centre uses multiple combination bactericidal testing ( mcbt ) when determining appropriate peritransplant prophylactic regimens . to evaluate our strategy , we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using mcbt versus standard sensitivity testing . \n \n patients with cf who were infected with pseudomonas aeruginosa and underwent lung transplantations between 2000 and 2010 were included . \n data was collected from clinical records and our microbiology database . \n microorganisms cultured were mapped against antibiotic resistance , method of sensitivity testing , and antibiotics administered peritransplant . \n \n 129 patients were identified ( mean age 28 , male : female , 63 : 66 ) . \n fifty patients ( 38.8% ) had antibiotics determined by mcbt . \n two patients in the mcbt group developed septicaemia , 13 in the conventional group ( p 0.05 , 2-tailed fisher 's test ) . \n sepsis was attributable to p. aeruginosa in one patient from the mcbt group and seven patients in the conventional group ( p = 0.15 ) . \n p. aeruginosa was recovered from the posttransplant pleural fluid of one patient who received mcbt - guided prophylaxis , six patients in the conventional group ( p = 0.25 ) . \n patients given antibiotics based on mcbt had significantly lower rates of septicaemia and lower rates of empyema .", "id": 871} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin a 2009 review paper , puhl and heuer documented the incredible scope of discrimination faced by overweight individuals , including in health care settings , the workplace , and media .\nin addition , they discuss the relatively sparse data on interventions aiming to eradicate these conditions ( puhl and heuer , 2009 ) . indeed , the few effective studies that have been published describe approaches primarily delivered to university students .\nsimilarly , the broader literature on curbing rates of victimization and bullying indicate that school - based approaches are most successful ( rigby and slee , 2008 ; ttofi and farrington , 2011 ; vreeman and carroll , 2007 ) .\noverall , it appears that intervening in secondary schools or universities may be an opportune time to target body dissatisfaction and discrimination related to weight more globally .\nlarge - scale , school - based interventions have been promising in regard to decreasing victimization among pre - adolescents and adolescents ( busch et al . , 2012 ;\n, the utrecht healthy school ( uhs ) program aimed to comprehensively improve healthy behaviors including eating habits , physical activity , and substance abuse , as well as decreasing bullying ( busch et al . , 2012 ) .\nthe uhs approach emphasizes involvement of students , teachers , parents , and administrators , as well as building external connections with an overall goal of health promotion for all members of the school community . with advisement from these stakeholders ,\nuhs was rolled out from 2007 to 2010 , and outcome assessment consisted of comparisons from two cohorts of students reporting in 2007 and 2010 .\nresults showed improvements in many of the target behaviors , including increased physical activity and lower rates of bullying and victimization ( busch et al . , 2012 ) .\na social and emotional learning ( sel ) curriculum aiming to improve mental health and related outcomes like victimization was developed and tested in sweden ( kimber et al . , 2008 ) .\nsel , based on cognitive and behavioral methods , focuses on helping students to develop the following five skills : self - awareness , managing one s emotions , empathy , motivation , and social competence .\nusing a quasi - experimental design , after 2 years of the program , results showed some important differences between outcomes for students in experimental and control schools including decreases in victimization ( kimber et al . , 2008 ) .\nimportantly , puhl and colleagues ( puhl et al . , 2013 ) surveyed adolescent recipients of weight - related victimization for their perspectives on intervention\nfor example , the importance of teaching student bystanders how to prevent rather than reinforce bullying behavior appears to be a desirable strategy that has also been shown to be effective ( rigby and slee , 2008 ; salmivalli et al . , 2011 ) . it may also be useful to consider strategies that have been employed directly to victims or those at risk .\nfor example , vessey and oneill ( 2011 ) used materials from the us health services resources administration s stop bullying now campaign to develop a group intervention for children with disabilities , who are at high risk for experiencing victimization .\nresults showed that group members were less bothered by teasing afterwards and also experienced improved self - concept .\nsimilarly , in hong kong , a 10-week cognitive behavioral program was delivered to 68 victims of bullying ( fung , 2012 ) .\nthe program yielded mixed results with students reporting decreased victimization although parents and teacher reports did not echo these findings .\noverall , these programs offer some suggestions for strategies that psychologists can draw from when addressing victim - blaming in therapy .\nit may also be useful to consider strategies that have been employed directly to victims or those at risk .\nfor example , vessey and oneill ( 2011 ) used materials from the us health services resources administration s stop bullying now campaign to develop a group intervention for children with disabilities , who are at high risk for experiencing victimization .\nresults showed that group members were less bothered by teasing afterwards and also experienced improved self - concept .\nsimilarly , in hong kong , a 10-week cognitive behavioral program was delivered to 68 victims of bullying ( fung , 2012 ) .\nthe program yielded mixed results with students reporting decreased victimization although parents and teacher reports did not echo these findings .\noverall , these programs offer some suggestions for strategies that psychologists can draw from when addressing victim - blaming in therapy .\nas marks ( 2015 ) states , the media promotes an unhealthy body image , in which most women seen in magazines and billboards are visibly underweight ( ahern and hetherington , 2006 ) . specifically , the media reinforces the perpetuation of the thin - ideal through the glorification of ultra - thin models , causing those who look to the media for information to internalize this ideal ( thompson and stice , 2001 ) .\nthe perceived discrepancy between people s ideal and actual body image , as well as the unrealistic nature of the ideal , can lead to body image dissatisfaction ( bessenoff and snow , 2006 ; gluck and geliebter , 2002 ) .\none particularly illuminating study demonstrated that after introducing prolonged television access in fijian adolescent girls , those with exposure to western television demonstrated significantly more disordered eating attitudes and behaviors than those without exposure ( becker et al . , 2002 ) .\n buys into socially defined ideals of attractiveness and engages in behaviors designed to approximate those ideals ( ahern and hetherington , 2006 ) and is one of the most important risk factors for the development of eating pathology ( stice and shaw , 1994 ) .\nthe body project , the most successful eating disorder prevention program , is a 4-session group - based intervention that utilizes the principle of cognitive dissonance .\nit requires participants to explore the costs of and to reject the thin - ideal , thereby reducing their thin - ideal internalization .\nextensive research on the body project has demonstrated a decrease in thin - ideal internalization that has led to significant and clinically meaningful reductions in body image dissatisfaction and negative affect ( two parts of the cod ) , as well as 60 percent reductions in diagnostic and statistical manual of mental disorders ( 4th ed .\n; dsm - iv ) eating disorders at 3-year follow up compared to controls ( stice et al . , 2013a , 2013b ) .\na large body of research has demonstrated the efficacy of the body project in reducing thin - ideal internalization , body image dissatisfaction , and negative affect in female college ( e.g. stice et al . , 2011 ) and high school students ( stice et al . , 2011 ) , although it has been less successful among middle school girls ( rohde et al . , 2014 ) .\ngiven its efficacy , efforts have been focused on improving the translatability of this intervention .\nrecent research has demonstrated support for a train - the - trainer approach to body project dissemination . specifically , when master trainers trained novice trainers to train undergraduate peer leaders , participants showed significantly reduced levels of thin - ideal internalization , body dissatisfaction , and disordered eating at post - treatment and 5-month follow up ( grief et al . , 2015 ) .\n2014 ) found that effects of the intervention were not related to facilitator s age , sex , education level , or body mass index ( bmi ) or the size of the group , which is encouraging for dissemination .\nother efforts to disseminate the intervention have included an internet - dissonance - based program , which demonstrated similar efficacy to an in - person group intervention at post - test , but improvements were not as well maintained at 1- and 2-year follow ups ( stice et al . , 2014 ) .\nalthough the majority of dissonance - based prevention programs have been geared toward the prevention of eating disorders , this recent study of the internet - based program ( ebody project ) also demonstrated large weight gain prevention effects , significantly more so than the body project , which were comparable to other obesity prevention programs ( stice et al . , 2014 ) .\nthus , at least for women and girls , these cognitive - dissonance - based programs can reduce body image dissatisfaction , and in some contexts , prevent weight gain . working toward eliminating obstacles to dissemination of this program may help to break the cod . the most obvious and likely effective way of devalorizing the thin - ideal is on a societal level , by diversifying representations of individuals of varying weights in the media and expanding access to larger sized clothing , for example .\nas these societal concerns are tackled , clinicians can also help to devalorize the thin - ideal on a more individual level .\nalthough not designed to target the thin - ideal directly , mirror exposure therapy is currently used to promote body image acceptance and reduce body image dissatisfaction . during exposure ,\npatients are asked to look at themselves in a mirror while describing their physical appearance in a neutral manner .\nstudies of mirror exposure have demonstrated significant reductions in body image dissatisfaction among adults with binge eating disorder ( hilbert et al . , 2002 ) , as well as overweight and obese adolescents ( jansen et al . , 2008 ) .\nin conclusion , it is important for psychologists to be aware of effective approaches available to intervene stemming from marks ( 2015 ) novel homeostatic theory .\nindeed , the literature has shown that there are both systemic and individual empirically supported interventions that can be employed by psychologists .\nin particular , such services can be feasibly and acceptably delivered to adolescents and young adults in school settings .\nit seems reasonable to suggest initiating large - scale programs in secondary schools and universities that perhaps can even be packaged together to most impactfully address circumstances intertwined with weight gain .\noverall , informed by theory , such culture changes may be an ideal way to focus prevention and intervention efforts .\nthin - ideal internalization is defined as the extent to which an individual buys into socially defined ideals of attractiveness and engages in behaviors designed to approximate those ideals ( ahern and hetherington , 2006 ) and is one of the most important risk factors for the development of eating pathology ( stice and shaw , 1994 ) .\nthe body project , the most successful eating disorder prevention program , is a 4-session group - based intervention that utilizes the principle of cognitive dissonance .\nit requires participants to explore the costs of and to reject the thin - ideal , thereby reducing their thin - ideal internalization .\nextensive research on the body project has demonstrated a decrease in thin - ideal internalization that has led to significant and clinically meaningful reductions in body image dissatisfaction and negative affect ( two parts of the cod ) , as well as 60 percent reductions in diagnostic and statistical manual of mental disorders ( 4th ed .\n; dsm - iv ) eating disorders at 3-year follow up compared to controls ( stice et al .\na large body of research has demonstrated the efficacy of the body project in reducing thin - ideal internalization , body image dissatisfaction , and negative affect in female college ( e.g. stice et al . , 2011 ) and high school students ( stice et al . ,\n2011 ) , although it has been less successful among middle school girls ( rohde et al . , 2014 ) .\ngiven its efficacy , efforts have been focused on improving the translatability of this intervention .\nrecent research has demonstrated support for a train - the - trainer approach to body project dissemination . specifically , when master trainers trained novice trainers to train undergraduate peer leaders , participants showed significantly reduced levels of thin - ideal internalization , body dissatisfaction , and disordered eating at post - treatment and 5-month follow up ( grief et al . , 2015 )\n2014 ) found that effects of the intervention were not related to facilitator s age , sex , education level , or body mass index ( bmi ) or the size of the group , which is encouraging for dissemination .\nother efforts to disseminate the intervention have included an internet - dissonance - based program , which demonstrated similar efficacy to an in - person group intervention at post - test , but improvements were not as well maintained at 1- and 2-year follow ups ( stice et al . , 2014 ) .\nalthough the majority of dissonance - based prevention programs have been geared toward the prevention of eating disorders , this recent study of the internet - based program ( ebody project ) also demonstrated large weight gain prevention effects , significantly more so than the body project , which were comparable to other obesity prevention programs ( stice et al . , 2014 ) .\nthus , at least for women and girls , these cognitive - dissonance - based programs can reduce body image dissatisfaction , and in some contexts , prevent weight gain . working toward eliminating obstacles to dissemination of this program may help to break the cod .\nthe most obvious and likely effective way of devalorizing the thin - ideal is on a societal level , by diversifying representations of individuals of varying weights in the media and expanding access to larger sized clothing , for example .\nas these societal concerns are tackled , clinicians can also help to devalorize the thin - ideal on a more individual level .\nalthough not designed to target the thin - ideal directly , mirror exposure therapy is currently used to promote body image acceptance and reduce body image dissatisfaction . during exposure ,\npatients are asked to look at themselves in a mirror while describing their physical appearance in a neutral manner .\nstudies of mirror exposure have demonstrated significant reductions in body image dissatisfaction among adults with binge eating disorder ( hilbert et al . , 2002 ) , as well as overweight and obese adolescents ( jansen et al . , 2008 ) .\nin conclusion , it is important for psychologists to be aware of effective approaches available to intervene stemming from marks ( 2015 ) novel homeostatic theory .\nindeed , the literature has shown that there are both systemic and individual empirically supported interventions that can be employed by psychologists .\nin particular , such services can be feasibly and acceptably delivered to adolescents and young adults in school settings .\nit seems reasonable to suggest initiating large - scale programs in secondary schools and universities that perhaps can even be packaged together to most impactfully address circumstances intertwined with weight gain .\noverall , informed by theory , such culture changes may be an ideal way to focus prevention and intervention efforts .", "answer": "marks presents homeostatic theory which proposes that weight gain is fostered by a circle of discontent consisting of body dissatisfaction , negative affect , and overconsumption . \n this innovative framework offers potential intervention approaches , including victim - blaming , stigma , and discrimination , as well as devalorizing the thin - ideal . \n our article discusses possible ways that clinical health psychologists based in university settings may be uniquely positioned to consider and implement large - scale programs that have shown great promise for addressing these core issues .", "id": 872} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin central europe patients with muscle - invasive bladder cancer ( mibc ) have relatively poor prognosis .\nthis includes also patients initially undergoing radical surgical treatment . in order to find underlying reasons ,\nwe have previously estimated the timing of radical cystectomy in a multicentre study involving 575 polish patients . however , one of the most important limitations of the abovementioned study was the inclusion criterion of being cystectomised instead of being diagnosed with mibc .\nconsequently , the data on final treatment in the whole population of mibc patients are still limited . within this short communication\nthe aim of this study was to describe patterns of care in polish patients with newly diagnosed mibc .\nthis is a multicentre retrospective cohort study involving 296 consecutive patients with primary mibc diagnosed in the years 20122013 in 13 polish urological centres . in all patients the diagnosis\nwas made based on histological examination of surgical specimens from transurethral resection of the bladder tumour .\nthe mean age of the cohort was 72.1 years and male - to - female ratio was 3.2 : 1 ( 225 vs. 71 ) .\ndifferences between cystectomised and non - cystectomised patients were evaluated with u mann - whitney test and test for quantitative and qualitative variables , respectively .\ncomparison of patients depending on qualification for radical cystectomy table presents absolute , median , or percentage values .\nhaemoglobin ; rc radical cystectomy data on nicotine use was available only in 220 patients ( 77.2% of cohort ) among 121/285 ( 42.5% ) patients disqualified from rc , 32/121 ( 26.4% ) patients were qualified for a second step of transurethral resection of the bladder tumour ( turbt ) intentionally followed by systemic chemotherapy , four ( 3.3% ) patients after complete turbt were qualified for adjuvant intravesical chemotherapy only , while the remaining 85 ( 70.2% ) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care .\ndespite poor outcomes of treatment of patients with mibc in central europe , data on patterns of surgical and medical management , as well as its quality , are still unavailable .\nwe performed a retrospective study aimed at the description of further treatment in patients diagnosed with primary mibc .\nthe most important finding of our analysis is the high percentage of patients qualified for radical treatment .\na clinically important fact is that that these numbers would probably be higher if we excluded from the analysis patients with metastatic disease , who are not candidates for rc by definition .\navailable data on patterns of care in mibc patients published in the last 10 years present significantly lower rates of curative treatment , covering 2152.5% of patients [ 47 ] .\nhowever , the studies cited above included more patients and/or were based on cancer or national registries .\nsome portion of patients included in these analyses was treated with radiotherapy alone , which nowadays is not regarded as a radical approach .\nwe have also found that patients disqualified from curative treatment were older , had lower bmi values , lower haemoglobin concentration , and declared lower rate of nicotine abuse and shorter time interval between first symptom to diagnosis . while age alone should not influence clinical decisions , it is suggested that older mibc patients are less frequently qualified for radical surgery , and it is well established that the morbidity related to rc is increased within this group [ 912 ] .\nlow haemoglobin concentration , as well as malnutrition is associated with shorter survival after rc [ 9 , 13 , 14 ] .\nmoreover , abnormal bmi value increases the risk of surgical complications [ 12 , 15 , 16 ] .\nour findings on nicotine use and time from first symptom to diagnosis are both surprising and unexplainable . considering the pathogenesis and clinical course of the disease\n, one can suspect that these results are fortuitous . finally , they are of no practical significance .\nthe study 's strengths are its multi - institutional character , involvement of both academic and non - academic urological departments , and enrolment of a representative cohort of patients .\nthe most important limitation of the study is the lack of data on lymph node and distant metastases . as available clinical staging\nis limited to regional status , among patients disqualified from surgery there are both patients unfit for surgery and patients with initially metastatic disease . their differentiation in the present study was not performed .\nbecause the majority of polish patients with primary mibc receive curative treatment , the stage of the disease alone seems not to be the leading cause of poor survival .\nhowever , the appropriateness of qualification for rc and treatment quality needs to be assessed for a final conclusion on the factors influencing outcomes of treatment in poland .\nthe results presented within this paper come from post hoc analysis of data collected during a multicentre study aimed at oncological characterisation of a large cohort of polish patients with primary urothelial carcinoma of the bladder .\nthe study was produced under the auspices of the residents section of the polish urological association .\nall the investigators , but two ( m.s . and p.r . ) , were urologists in training .", "answer": "a potential reason for poor survival among patients with muscle - invasive bladder cancer ( mibc ) in poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status . \n the aim of this study was to describe patterns of care in patients with newly diagnosed mibc.this is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed mibc . therapeutic decisions and potentially underlying clinical factors were analysed.full clinical data was available for 285 patients . \n one hundred and sixty - four ( 57.5% ) patients were qualified for radical cystectomy ( rc ) , 32 ( 11.2% ) patients for a second step of transurethral resection of the bladder tumour ( turbt ) intentionally followed by systemic chemotherapy , four ( 1.4% ) patients after complete turbt were qualified for adjuvant intravesical chemotherapy only , while the remaining 85 ( 29.8% ) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care . \n patients disqualified from curative treatment were older ( 78 vs. 69 years , p < 0.02 ) , had lower bmi values ( 24.5 vs. 25.7 kg / m2 , p < 0.02 ) , lower haemoglobin concentration ( 11.6 vs. 12.9 mg / l , p < 0.02 ) , declared lower rate of nicotine abuse ( 50.5% vs. 72.1% , p < 0.02 ) , and had a shorter time interval between first symptom and diagnosis ( 30 vs. 60 days , p = 0.02).as the majority of polish patients with primary mibc receive curative treatment , the stage of the disease alone seems not to be the leading cause of poor survival . \n however , appropriateness of qualification for rc and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in poland .", "id": 873} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nosteoporosis is a disease characterized by the structural deterioration of bone and low bone mass .\nthe world health organization defines osteoporosis as a bone mineral density ( bmd ) value of 2.5 standard deviations or more below the young adult mean.1 an estimated 10 million patients in the united states have osteoporosis , and its prevalence is expected to continue to rise in the world population.2 degenerative spondylolisthesis and spinal stenosis , as well as vertebral compression fractures , have been reported at an increased rate in patients with osteoporosis,3 and the disease requires special consideration for any older patient undergoing spine surgery . obtaining optimal fixation in the osteoporotic spine is technically challenging ; osteoporosis may also be associated with a poor fusion rate , with rates as low as 56% in elderly patients.4 however , for appropriately selected patients , the presence of osteoporosis is not a contraindication to surgical intervention . very little available literature exists specifically evaluating the clinical and radiographic outcomes in patients with osteoporosis undergoing transforaminal lumbar interbody fusion ( tlif ) .\nin fact , to our knowledge , no previous study has examined the effect that osteoporosis may have on rates of interbody cage subsidence , migration , pedicle screw loosening , or iatrogenic fractures in patients undergoing instrumented tlif .\ntherefore , we sought to compare the radiographic and clinical outcomes of tlif in patients with and patients without osteoporosis .\nafter institutional review board approval , we retrospectively reviewed all patients aged 50 years or older undergoing instrumented tlif for any indication at one of three institutions between july 2004 and june 2014 .\nonly patients with immediate postoperative and follow - up radiographs and computed tomography ( ct ) scans available for evaluation of the interbody cage were included in the study .\nwe excluded all patients without at least a 6-month follow - up ct scan . utilizing a technique similar to that described by lee et al,5 we measured ct hounsfield units ( hus ) on the lumbar vertebrae for all included patients using preoperative ct scans .\npatients were then stratified as either osteoporotic or nonosteoporotic based on average lumbar vertebral body hu values .\nthe hu cutoff values were previously determined from a separate study at our institution and found to correlate with bmd obtained from dual - energy x - ray absorptiometry ( dexa ) scans ( p.m. formby et al , personal communication ) .\npatients with hu 112.4 were considered osteoporotic , and those with hu > 112.4 were considered nonosteoporotic .\nplain radiographs and ct scans were evaluated for evidence of implant subsidence , migration , interbody fusion , iatrogenic fracture , or loosening of posterior pedicle screw fixation .\npatient medical records were then reviewed for postoperative symptoms , which were further subdivided into persistence of symptoms or recurrence of symptoms .\nwe used the student t test to evaluate continuous variables and mid - p exact tests for dichotomous data , and p values 0.05 were considered statistically significant .\ntwenty - five ( 19.5% ) of these patients were designated as osteoporotic based on the postoperative ct hu measurements versus 103 ( 80.4% ) patients without osteoporosis .\nwe excluded 40 patients who did not have at least a 6-month follow - up ct imaging , leaving 18 ( 20.5% ) patients with osteoporosis and 70 ( 79.5% ) patients without osteoporosis .\nthese patients had a mean radiographic follow - up of 35.8 27.9 months .\nthe mean age was significantly higher in the osteoporotic group ( 65.2 years ) versus the nonosteoporotic group ( 56.9 years , p < 0.0001 ) .\nmales comprised 50 and 64.3% of the osteoporotic and nonosteoporotic patient groups , respectively , with a combined mean age of 58.5 7.9 years .\nwe found no significant differences between the osteoporotic and nonosteoporotic groups with regard to sex ( p = 0.28 ) , body mass index ( 27.6 versus 29.9 , p = 0.12 ) , number of identified medical comorbidities ( 2.3 versus 1.8 , p = 0.15 ) , total number of vertebral levels fused ( 1.9 versus 1.8 , p = 0.56 ) , or fusion rate ( 83.3 versus 88.6% , p = 0.56 ) .\nthere were no statistically significant differences between groups for gross implant migration in the coronal or sagittal planes ( 11.1 versus 1.4% , p = 0.11 ) , pedicle screw loosening ( 22.2 versus 8.6% , p = 0.14 ) , revision surgery ( 16.6 versus 14.3% , p = 0.78 ) , or postoperative symptoms ( 44.4 versus 50.0% , p = 0.69 ; tables 1 , 2 ) .\nthere were no statistically significant differences between the osteoporotic and nonosteoporotic groups in persistent or recurrent symptoms , though the rate of recurrence in the nonosteoporotic group was three times higher ( persistent symptoms : 38.9 versus 30.0% , p = 0.47 , respectively ; recurrent symptoms : 5.6 versus 18.6% , p = 0.18 , respectively ) . abbreviations :\nbmi , body mass index ; ca / vit d , calcium / vitamin d ; dexa , dual - energy x - ray absorptiometry ; hu , hounsfield units .\nnote : the only significant differences between the osteoporotic and nonosteoporotic groups were for mean patient age and hu measurements .\nnote : the rates of interbody cage subsidence , iatrogenic fracture , and overall complication rates were higher in the osteoporotic group\n. significantly higher rates of subsidence ( 5.6 2.4 [ 72.2% ] versus 5.2 1.9 [ 45.7% ] , p = 0.05 ) and iatrogenic fractures ( 16.7 versus 1.4% ,\noverall , the osteoporotic population had significantly higher radiographic complication rates compared with patients without osteoporosis ( 77.8 versus 48.6% , p = 0.03 ; table 2 ) .\nas the average life expectancy continues to increase in the united states , spine surgeons should expect to manage a greater proportion of elderly patients with degenerative spinal conditions .\nconcomitant with increasing age is an associated increase in the prevalence of osteopenia and osteoporosis . in a study of patients over the age of 50 years undergoing spinal surgery in south korea ,\nchin et al found osteopenia and osteoporosis rates of 41.4 and 51.3% , respectively , based on dexa.3 despite the growing population of elderly patients , however , few studies have evaluated the role that low lumbar bmd may have in the complication rates and overall outcomes of patients undergoing lumbar interbody fusion .\nwe found that a minority of patients ( 21.5% ) undergoing tlif had any dexa information available at the time of surgery , despite advancing age and clinical risk factors for osteoporosis . utilizing hu measurements to assess lumbar vertebral body bmd\n, we found that of the patients with hu values consistent with osteoporosis , only 27.8% had any workup for osteoporosis prior to or following their tlif .\nthis finding is concerning , particularly because we found a higher overall radiographic complication rate in patients with osteoporosis undergoing tlif , and it suggests that patients are undergoing spinal fusion surgery without being appropriately evaluated for low bmd . although there were few patients with osteoporosis in this study , we found an increased incidence and amount of cage subsidence ( fig .\n1 ) , a higher rate of iatrogenic fractures , and more overall radiographic complications in patients with osteoporosis . though our data did not reach statistical significance , we also found a greater propensity for implant migration and posterior pedicle screw loosening . \n\n( a ) immediate postoperative and ( b ) 2-year follow - up sagittal computed tomography ( ct ) scans of a 53-year - old man who underwent l4l5 transforaminal lumbar interbody fusion .\nthe patient had hounsfield unit ( hu ) measurements on immediate postoperative ct scan consistent with osteoporosis ( average l4 hu = 105.7 ) .\ninterbody cage subsidence into the superior end plate of l5 with interspace collapse is evident ( 9.9 mm ) , with evidence of increased fusion mass in the anterior column .\nhowever , at 26-month clinical follow - up , he had no recurrence of symptoms . however , it is important to note that the increased overall radiographic complication rate did not necessarily portend worse clinical outcomes for patients with osteoporosis .\npatients with osteoporosis and patients without osteoporosis underwent similar rates of revision surgery ( 16.7 versus 14.3% , respectively ) , and patients without osteoporosis actually had a higher prevalence of postoperative symptoms following tlif , particularly when stratifying the constellation of symptoms based on persistence versus subsequent recurrence of symptoms : we found that the rate of recurrent symptoms was higher in the nonosteoporotic group ( 18.6 versus 5.6% , respectively ) , although this finding also did not reach statistical significance .\nit is unclear , however , why this trend was observed , and it may be related to the fact that we only included patients with six - month or later postoperative ct scans in our study , which may have biased our clinical data with an increased proportion of patients with postoperative symptoms . despite a higher interbody cage subsidence rate in the osteoporotic group , which in turn would theoretically lead to loss of foraminal height and eventual recurrence of radiculopathy , there did not appear to be any association between osteoporosis and recurrence of symptoms .\nwe are unaware of any other studies specifically evaluating postoperative radiographic complications in patients with osteoporosis undergoing tlif .\nprevious studies have drawn conflicting conclusions regarding whether elderly patients are at increased risk for postoperative complications following lumbar fusion .\ncarreon et al found a 79.6% rate of postoperative complications in patients 65 years old at the time of posterior lumbar instrumented fusion.6 however , cassinelli et al found a much lower rate of major complications ( 3% ) and minor complications ( 31% ) in a similar cohort of patients 65 years undergoing instrumented and noninstrumented lumbar spine arthrodesis.7 similarly , cavagna et al evaluated patients > 65 years undergoing instrumented lumbar fusions and found good clinical outcomes and no serious postoperative complications or reoperations in this cohort.8 however , they did find a 10.3% rate of implant failure ( two screws and two rods failed ) at 2-year or later follow - up .\nglassman et al investigated clinical outcomes of patients 65 years old compared with those < 65 years old undergoing single - level instrumented posterolateral lumbar arthrodesis ; the authors found that the older population had similar clinical and health - related quality - of - life improvements when compared with the younger cohort.9 however , the older cohort experienced significantly increased rates of serious ( 38 versus 17% ) and overall adverse postoperative events ( 56 versus 36% ) , although there was no increased risk of revision or reoperation between these groups .\nlikewise , okuda et al did not find major differences in clinical outcomes between patients 70 years old and those < 70 years old undergoing instrumented lumbar interbody fusion.10 these authors found no increased risk or instrument failure between groups , although they did find lower rates of fusion and higher rates of collapsed union and delayed union in the elderly group.10 \n inherent to any small retrospective study , the possibility of type ii statistical error limits the generalizability of our analysis .\nthe proportion of patients with osteoporosis in our study was low , which could be a source of bias .\nour study was also limited by the quality of the medical records , as well as available radiographs and ct scans .\nin addition , despite a minimum age of 50 years for inclusion in this study , our patients were still relatively young and healthy , with few comorbidities and a mean age of only 58.5 years .\nwe looked at a heterogeneous group of patients with disparate preoperative diagnoses undergoing tlif for any reason , which could contribute to bias in this study .\nthe use of hu for measurement of bone density has not been validated in the literature , with few reports of its use to date .\nfurther prospective studies are needed to evaluate the role that osteoporosis plays in complication rates and overall clinical outcomes in patients undergoing lumbar fusion surgery .\nin conclusion , we found significantly increased rates of cage subsidence , iatrogenic fractures , and overall radiographic complications in patients with osteoporosis undergoing tlif .\nhowever , these radiographic complications did not predispose patients with osteoporosis to worse clinical outcomes , and larger , prospective studies are needed to further evaluate lumbar fusion surgery in patients with osteoporosis .", "answer": "study design retrospective review . \n \n objective to compare clinical outcomes after transforaminal lumbar interbody fusion ( tlif ) in patients with and patients without osteoporosis . \n \n methods we reviewed all patients with 6-month postoperative radiographs and computed tomography ( ct ) scans for evaluation of the interbody cage . \n ct hounsfield unit ( hu ) measurements of the instrumented vertebral body were used to determine whether patients had osteoporosis . \n radiographs and ct scans were evaluated for evidence of implant subsidence , migration , interbody fusion , iatrogenic fracture , or loosening of posterior pedicle screw fixation . \n medical records were reviewed for persistence of symptoms or recurrence of symptoms . \n \n results the final data analysis included 18 ( 20.5% ) patients with osteoporosis and 70 ( 79.5% ) patients without osteoporosis . males comprised 50% of patients with osteoporosis , and 64.3% of patients without osteoporosis . \n the mean age was significantly higher in the osteoporotic group ( 65.2 years ) versus the nonosteoporotic group ( 56.9 years ; p < 0.0001 ) . \n we found significantly higher rates of subsidence ( 72.2 versus 45.7% , p = 0.05 ) and iatrogenic fractures ( 16.7% versus 1.4% , \n p = 0.03 ) in the osteoporotic group . in addition , the osteoporotic group had significantly higher radiographic complication rates compared with the nonosteoporotic group ( 77.8 versus 48.6% , p = 0.03 ) . \n there was no difference between groups for revision surgery ( 16.6 versus 14.3% , p = 0.78 ) or postoperative symptoms ( 44.4% versus 50.0% , p = 0.69 ) . \n \n conclusions our data demonstrated significantly increased rates of cage subsidence , iatrogenic fracture , and overall radiographic complications in patients with osteoporosis \n . however , these radiographic complications did not predispose patients with osteoporosis to an increased risk of surgical revision or worse clinical outcomes .", "id": 874} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnearly , 90% of metastatic tumors occur in jaw bones , especially premolar - molar region of the mandible , whereas metastases to soft tissues are extraordinarily rare and account for 0.1% of all oral malignancies .\nmost metastatic tumors to the orofacial region are seen in patients aged between 40 and 70 years .\nmetastasis to the soft tissues mostly involves gingiva and alveolar mucosal sites ( 54% ) followed by tongue ( 30% ) . in some cases ,\noral metastatic tumors are found to be the first sign of metastatic spread and in some instances ; they are an indication for unidentified primary tumor of the distant site .\nthe primary site differs according to oral site colonization . in men , primary tumor of the lung followed by the prostate gland and kidney\nthe breast is the most common primary tumor site affecting the jawbones and soft tissues ( 41% and 24.3% , respectively ) , followed by the adrenal and female genital organs .\nclinically , these metastatic lesions appear nonaggressive , mimicking reactive or benign lesions or even simple odontogenic infections . the clinical features of these lesions include a bony swelling with tenderness , pain , ulcer , hemorrhage , paresthesia and pathological fracture .\nit is important to diagnose the origin of the tumor as the management will depend significantly on the histological type .\nalthough infrequent , oral metastases are rarely encountered as the first sign of occult cancer .\nhence , this article emphasizes on detailed dentoalveolar examination and early diagnosis for finding the primary focus of metastatic tumor .\na 60-year - old male patient presented with a swelling in the right lower back teeth region of the jaw since 3 months [ figure 1 ] .\nthe patient complaints of pain for 10 days , radiating to the right temporal region .\nthe patient was a known hypertensive since 4 years . a well - defined solitary swelling present on the right side of mandible on extraoral examination , a well - defined , solitary swelling measuring 4 cm\n 5 cm was noted on the right side of the mandible , which was hard in consistency and fixed to the underlying skin .\nno other pathologic findings were noticed during physical examination . on intraoral examination , firm ,\nnontender swelling with ill - defined borders measuring 3 cm 3 cm was noted in the right mandibular premolar - molar region [ figure 2 ] .\nthere was no ulceration , paresthesia or pathological fracture . on intraoral examination , firm ,\nnontender swelling with ill - defined borders measuring 3 cm 3 cm was noted patient was advised for oral pantamograph and computed tomography ( ct ) scan .\nct scan of the face with three - dimension reconstruction revealed a well - defined osteolytic lesion involving the ramus and body of the right half of the mandible , measuring 54 mm 45 mm 50 mm ( anterioposterior transverse craniocaudal ) .\nit showed speculated periosteal lesion with multiple irregular calcifications and extended into the lingual and mandibular soft tissues [ figure 3 ] .\nbased on the clinical presentation , a differential diagnosis of inflammatory swelling , odontogenic cyst , odontogenic tumor , soft tissue tumor or metastatic tumor to the jawbones was given .\ncomputed tomography scan of the face with three - dimensional reconstruction revealed a well - defined osteolytic lesion with multiple irregular calcifications that extended into the lingual and mandibular soft tissues incisional biopsy was done for the histopathological diagnosis .\nhistopathological examination of the h and e stained tissue showed diffuse fibrous connective tissue stroma invaded by the tumor cells which were cuboidal to short columnar with eosinophilic cytoplasm arranged in alveolar / follicular pattern of varying sizes [ figure 4 ] .\nbony trabeculae were evident in some areas [ figure 5 ] . based on these features ,\nthe lesion was diagnosed as a metastatic malignant tumor , probably metastasizing from the lung .\n( h&e stain , 100 ) tumor islands along with few bony trabeculae were evident in some areas .\n( h&e stain , 40 ) x - ray chest posterior - anterior view revealed consolidation of the right lower zone [ figure 6 ] .\nthe ct scan of the chest with contrast revealed dense soft tissue mass lesion with speculated margins and focal pleural thickening noted at the right posterior basal segment .\nx - ray chest posterior - anterior view revealed consolidation in right lower zone of the lungs treatment for the patient was palliative external beam radiotherapy on linac given to a total dose of 3000 cgy in 10 fractions to jaw by rl / ll for 12 days which was well - tolerated by the patient .\nchemotherapy included injection cisplatin ( 75 mg)-intravenous ( iv ) ; injection etoposide ( 150 mg)-iv ; tablet vomiset ( 8 mg ) ; tablet ultracet .\nthe common primary sources of tumors metastatic to the oral region are the breast , lung and kidney .\nthe actual incidence of these cancers is unknown since oral metastatic disease is usually a manifestation of advanced disease .\nthe mean age of occurrence is 54 years with slight male predilection . in our case ,\nalso the patient was aged about the same age ( 60 years ) as supported in the literature .\nmost of the patients are aware of primary tumors before the metastatic spread to the oral cavity . in our case ,\nthe most common primary sites for oral metastases were the lung , kidney , liver and prostate for men ; breast , female genital organs , kidney , and colorectum for women . in our case too , lung was found to be the primary site .\nthe clinical presentation of the metastatic lesions differed between the various oral sites . in the jawbones ,\nmost of the patients complain of rapidly progressing swelling , pain , paresthesia , difficulty in chewing , dysphagia , disfigurement and bleeding .\nour patient presented with features such as firm , nontender swelling with ill - defined borders .\nthere was no paresthesia , difficulty in chewing , dysphagia , bleeding and pathological fracture .\npathogenesis of oral metastasis is unclear but thought to be a multistage process in which cells detach themselves from the primary tumor and get transported by lymphatic or blood vessels .\nrecent studies state that cancer cells metastasizing to bone have shown to alter the physiologic balance between both bone resorption and bone formation .\ntreatment of oral metastasis depends upon its presentation and the stage during which it has been identified .\nmanagement includes chemotherapy , radiotherapy , surgical excision or a combination of the techniques under local anesthesia .\nan average survival time for lung cancer metastasis is 4 months to 1 year with a maximum survival rate of 5 years .", "answer": "oral cavity is an uncommon site for metastasis and is usually an evidence of widespread disease . \n the clinical presentation of the metastatic lesions differs between the various sites in the oral region . \n metastatic tumors account for 13% of all oral malignancies . \n the jawbones , particularly the mandibular molar area is more frequently affected than the oral soft tissues ( 2:1 ) . here , we report a case of a 60-year - old male patient with metastasis from lung to the mandible , where the metastasis was detected before primary tumor .", "id": 875} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 60-year - old lady presented to our sister department of medical gastroenterology at a tertiary health care institute with a history of an increasing mass in the right upper abdomen of one and a half year duration .\nshe also had a history of weight loss due to early satiety and decreasing appetite .\nshe had been evaluated with abdominal cect 14 months before by some local doctor which had shown a mass lesion in the right lobe of the liver .\nall her systemic examinations were normal except a big nodular mass in the right hypochondrium merging with the liver .\nthe department of medical gastroenterology considered her for a repeat workup , with abdominal mri , rbc trigged nuclear scan of the liver , serum tumor markers and routine base investigations .\nmri showed a nodular mass lesion arising from the right lobe of the liver , crossing towards the left lobe with involvement of the right portal vein , with areas of cystic changes and hemorrhage within the lesion ( fig .\nher tumor markers , including -fetoprotein , cea , ca 19 - 9 and hcg , were all within normal limits .\nshe was also subjected to upper and lower gastrointestinal endoscopy to rule out any occult primary lesion in the gastrointestinal tract .\nroutine laboratory investigations including liver function tests , hemogram , kidney function , chest x - ray and ecg were within fairly normal limits , her coagulogram revealing pt elevated by 3 s. serology was negative for hepatitis b and c. she was also subjected to usg guided fnac which was inconclusive and revealed only blood cells .\nafter complete workup with a tentative diagnosis of fibrolamellar hepatocellular carcinoma the patient was referred to our department for surgical intervention . she was offered a diagnostic and if possible curative laparotomy after repeat imaging ( abdominal cect ) as she had again lapsed a period of 34 months after her workup . due to monitoring constraints\n, her attenders did not agree to get an abdominal ct but were ready for any possible surgical intervention with the minimum of a biopsy to plan further treatment . on exploration\nthe patient was found to have nodular bilobular disease occupying almost all of the liver .\nthere were areas of boggy swelling in between firm nodules predominantly on the inferior surface of liver suggestive of bleeding within the tumor on aspiration .\nthe lesion involving both lobes of the liver was too big and multicentric for any resectional procedure and so a biopsy from the lesion was taken safely .\nafter getting her histopathological report the patient was referred to a medical oncologist for further treatment .\nthis is the first case of fibrosarcoma of the liver reported at our institute . on light\nmicroscopy the tumor revealed homogeneous , spindle - shaped cells with abundant collagen fibers showing a classic herringbone pattern ( fig .\ntissue samples were then sent to another referral cancer hospital for immunohistochemistry where immunoreactive vimentin was found in the tumor cells .\nelectron microscopically , the tumor cells were rich in rough endoplasmic reticulum without a basement membrane and were surrounded by large amounts of collagen fibers .\nthe purpose of this case report is to share information on a rare tumor of the liver , a primary fibrosarcoma , as up to the late seventies the literature about this entity was restricted to autopsy diagnosis . to our knowledge\nthere are case reports from various parts of the world [ 2 , 3 ] , but there are no series of cases of primary fibrosarcoma of the liver .\netiologically exposure to cadmium has been linked to carcinogenesis of this disease in animal models .\ndescribed a series of 20 cases of sarcomatous tumors of the liver , of which angiosarcoma was the commonest , and concluded that primary treatment is surgery with survival depending on the degree of differentiation . from the available literature , primary treatment to be considered for fibrosarcoma of the liver\nis surgery with curative intent . in a recent article from sloan - kettering cancer center , between 1981 and 2004 they identified only 30 cases of primary liver sarcomas of which\nmost cases ( 10 ) were hemangioendotheliomas and only 3 were diagnosed to be primary fibrosarcoma .\nonly 11 of these patients underwent r0 resection and this group of resected tumors had a 5-year survival rate of 65% .\nunfortunately our patient presented quite late in the course of disease even if we consider her first ct scan done one and a half year back .\nthere is a report of one patient with primary fibrosarcoma presenting with frequent episodes of hypoglycemia , where insulin - like growth factor ii was intensely stained in the golgi area of the tumor cells , suggesting its role in the mechanism of hypoglycemia .\non histopathological examination these neoplasms show typical light microscopic features like that of malignant rhabdoid tumor with filamentous cytoplasmic inclusions ( fig .\n4 ) , and on electron microscopic examination show staining for both cytokeratin and vimentin by immunohistochemistry . after making a diagnosis of primary fibrosarcoma of the liver at an inoperable stage ,\nan extensive review of the literature regarding the role of other treatment modalities was done which was not encouraging [ 5 , 8 ] . though few reports recommend chemotherapy in liver metastasis of retroperitoneal fibrosarcoma consisting of cyclophosphamide , vincristine , farmorubicin , and dacarbazine , there is no definite role as treatment for primary lesion of liver .\noverall the prognosis reported by most of the authors is dismal [ 1 , 2 , 3 , 10 ] .\nwe conclude by passing on the message that this rare entity does exist and is an area for workup to make guidelines for management of such tumors .\nthis may be one of the few reported cases of primary hepatic fibrosarcoma confirmed by immunohistochemistry and electron microscopy .", "answer": "a 60-year - old lady presented to us with a right upper abdominal mass . with a clinical diagnosis of liver tumor , she was evaluated with abdominal ct , mri , nuclear scan , tumor markers , usg guided fnac and other baseline investigations . \n on evaluation she had a massive right lobe tumor crossing the midline . in view of the ambiguous diagnosis \n she was subjected to laparotomy where the lesion was judged unresectable and a biopsy was taken . \n histopathological examination showed the rare pathology of primary fibrosarcoma of the liver with features of homogeneous , spindle - shaped cells with abundant collagen fibers showing a classic herringbone pattern . \n tissue samples were then sent to another referral cancer hospital for immunohistochemistry and immunoreactive vimentin was found in the tumor cells . \n electron microscopically , the tumor cells were rich in rough endoplasmic reticulum without a basement membrane , and were surrounded by large amounts of collagen fibers . \n the fibroblastic character of the tumor cells was suggested by light and electron microscopy .", "id": 876} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nDesign and synthesis of non-hydrolyzable homoisoprenoid \\xce\\xb1-monofluorophosphonate inhibitors of PPAPDC family integral membrane lipid phosphatases\n\nPaper sections:\n\nFarnesyl diphosphate (FPP, 1) is a key intermediate in the mevalonate pathway for the biosynthesis of cholesterol and is the precursor for the biosynthesis of geranylgeranyl diphosphate (GGPP, 2), ubiquinone, heme and dolichol.1, 2 FPP and GGPP also function as prenyl donors for the isoprenylation of many proteins involved in cell growth and proliferation.3\u20135 The mevalonate pathway makes these isoprenoid diphosphates without synthesizing the corresponding isoprenols.6 However, isoprenols such as farnesol 3 and geranylgeraniol 4 are produced in cells and tissues by sequential enzymatic dephosphorylation of their diphosphates (Scheme 1).7, 8
PDP1/PAPDC2 in mammalian cells decreases protein isoprenylation and results in defects in cell growth and Cultured cells can incorporate exogenously provided isoprenols into sterols and proteins which requires their conversion to the corresponding diphosphates.7, 9\u201313 Together, these observations identify a route for interconversion of isoprenols and isoprenoid diphosphates that is independent of the mevalonate pathway. This process may enable recycling of \"scavenged\" isoprenols or could allow independent regulation of flux or substrate channeling to produce individual mevalonate pathway endproducts which have diverse functions.
Two members of the phosphatidic acid phosphatase domain containing (PPAPDC) class of integral membrane phosphatases are broad specificity lipid phosphomonoesterases that exhibit a preference for lipid diphosphate substrates including isoprenoid diphosphates.7, 14, 15 In vitro, one of these enzymes, PDP1/PPAPDC2 can catalyze the sequential hydrolysis of isoprenoid diphosphates first to the corresponding monophosphate and then to the isoprenol. Overexpression of PDP1/PAPDC2 in mammalian cells decreases protein isoprenylation and results in defects in cell growth and cytoskeletal organization that are associated with dysregulation of isoprenylated Rho family of GTPases suggesting that this enzyme may be a functionally involved in interconversion of isoprenols and isoprenoid diphosphates. Two related proteins PPAPDC1A and PPAPDC1B are also broad specificity enzymes. While their activities against isoprenoid diphosphates have not been reported, in vitro both enzymes actively hydrolyze the plant lipid diacylglycerol pyrophosphate (DGPP). Studying the physiological functions of these PPAPDC2 family proteins is hampered by the lack of small molecule probes and selective inhibitors. Thus, we have prepared a series of metabolically stabilized isoprenoid monophosphate mimics that we show are inhibitors of a representative member of the PPAPDC family of integral membrane lipid phosphatases.
Phosphonates are commonly used as hydrolytically stabilized analogues of phosphate monoesters.16\u201319 Metabolically stabilized inhibitors of protein farnesyl transferase based on farnesyl-\u03b1-difluoromethlenephosphonate have been prepared.20 Recent experimental studies indicate that the \u03b1-monofluoromethylene phosphonate is a better mimic of phosphate monoesters than either the methylene or difluoromethylene derivatives and the utility of this moiety as a probe of biochemical function has been demonstrated in recent years.21\u201324 We had previously shown that analogues of FPP where the isoprene units were replaced by substituted aniline moieties, (Scheme 1, AGPP 5), can serve as substrates for a variety of isoprenoid diphosphate utilizing enzymes, including the PPAPDC family integral membrane phosphatases and the protein prenyl transferases FTase and GGTase.25\u201327 In addition, an unidentified cellular pathway, possibility involving a kinase, converts isoprenols 3, 4, and AGOH 6 to their corresponding diphosphates 1, 2, and 5.7 We took advantage of this substrate promiscuity to design potential inhibitors based on both natural and unnatural aniline substituted isoprenoids.
The synthetic strategy for the target \u03b1-monofluorophosphonates is outlined in scheme 2 and was based on installing the fluorine prior to incorporation of the aniline group, followed by revealing the charged phosphonic acid in the last step by deprotecting the phosphonate esters with trimethylsilyl bromide (TMSBr). This strategy enables the introduction of structural diversity into the isoprenoid moiety after establishing the common \u03b1-monofluoromethylene replacement of the bridging phosphate ester oxygen.
Our initial approach was to incorporate the \u03b1-fluoromethlenephosphonate diester en bloc. Attempts to alkylate (EtO)2P(O)CFHZnBr or (EtO)2P(O)CFHCu or the \u03b1-lithiated \u03b1-fluoro-trimethylsilylphosphonate carbainion made from diethyldibromofluoromethylphosphonate with geranyl bromide proved unsuccessful in our hands.28, 29 The failure of these approaches led us to abandon the \u03b1-flurophosphonate moiety as a synthon and incorporate the fluorine via electrophilic fluorination with N-fluorobenzenesulfonamide (NFBS). Of the available electrophilic fluorinating agents, NFBS was chosen for its selective reactivity under mild conditions and ease of handling and storage.30,31,32 Accordingly, lithiation of either commercially available dimethyl or diethylmethylphosphonate, followed by alkylation with either geranyl or farnesyl bromide gave 7a-b and 8a-b in quantitative yield.19 Treatment of phosphonate 7a-b with n-butyllithium at -98\u00b0C in THF/HMPA generated the lithiated carbanion which was fluorinated using NFBS to give \u03b1-fluorophosphonate 9a-b in 71% and 68% yield respectively. The yield of \u03b1-monofluorophosphonate was reduced or absent when other bases such as LiHDMS, KHDMS or t-BuLi as well as when different solvent mixtures were employed (Table 1). The yield of \u03b1-monofluorophosphonate was also reduced to 38% when the diethyl ester 8a-b was used, suggesting that steric bulk around the phosphonate interferes with anion access to NFBS. Optimum deprotection of \u03b1-monofluorophosphonates 9a and 9b was achieved using a 15:30:1 molar ratio of TMSBr, pyridine and the phosphonate diester at 0\u00b0C for 45 min. followed by quenching with ice-cold water and stirring for another 4 hr at 0\u00b0C. TMSBr alone, other ratios of TMSBr and pyridine or stirring with aq. alkali for several days resulted in difficult to separate mixtures of partially hydrolyzed esters and other byproducts.19, 33 Attempt to optimize deprotection of ethyl esters 10a-b only gave partially hydrolyzed compounds along with starting material.
We then adapted our previously reported strategy for the synthesis of anilinogeraniol derivatives to prepare \u03b1-monofluorophosphonates 16a-f as outlined in scheme 2.34 Oxidation of phosphonates 9a with SeO2 provided the corresponding mixture of allylic alcohol 12 and aldehyde 13 respectively.10, 34 The alcohol 12 was recovered and oxidized to the desired aldehyde 13 with manganese dioxide. Reductive amination of the appropriate anilines 14a-f with aldehyde 13 using NaBH(OAc)3 gave \u03b1-monofluorophosphonate esters 15a-f. As expected from previous work, reductive amination of the anilines with the \u03b1,\u03b2-unsaturated aldehyde gives a mixture of cis/trans isomers about the 7,8 double bond in an approximately 1:10 ratio.34 Attempts to separate the isomers by column chromatography, silica-HPLC, or reverse-phase HPLC were unsuccessful. Deprotection of the phosphonate esters with the optimized TMSBr/pyridine conditions gave the desired \u03b1-monofluorophosphonic acids 16a-f which were stored at \u221220\u00b0C immediately after purification.
We used membranes from insect cells expressing PPAPDC1b as a source of activity to investigate the ability of the \u03b1-monofluorophosphonates to inhibit dephosphorylation of lipid phosphate substrates by this enzyme. Like PPAPDC2, PPAPDC1B hydrolyzes the representative substrate diacylglycerol pyrophosphate presented in mixed phospholipid and detergent micells with an apparent KM of 130 \u03bcM (Figure S1, supplementary data). A more detailed characterization of the PPAPDC1B enzyme will be published elsewhere. Phosphatase activity was determined in assays containing a fixed 10 \u03bcM concentration of the indicated \u03b1-monofluorophosphonates and the data are presented as a % inhibition observed in reactions containing 400 \u03bcM 1,2-dioctanoyl-sn-glycerol 3-phosphate (DGPP) substrate. Assuming a purely competitive mode of inhibition, the most potent of these compounds 16d, 16e and 16f inhibit PPAPDC1B activity with Ki values of ~10 \u03bcM. (Table 2). Phosphonate analogues of phosphatidic acid are competitive inhibitors of the related enzyme PPAPDC2 with comparable inhibition constants (Ki = 0.4 \u03bcM).35 These new inhibitors are therefore promising chemical tools to investigate the biological function and substrate-activity relationship of PPAPDC family of integral membrane lipid phosphatases and may prove to be of value for further investigations of the interconversion of isoprenoid diphosphates and their corresponding isoprenols in regulation of the mevalonate pathway.
", "answer": "An efficient, diversity oriented synthesis of homoisoprenoid \\xce\\xb1-monofluorophosphonates utilizing electrophilic fluorination is presented along with their activity as inhibitors of PPAPDC2 family integral membrane lipid phosphatases. These novel phosphatase-resistant analogues of isoprenoid monophosphates are a platform for further structure-activity relationship studies and provide access to other isoprenoid family members where the phosphate ester oxygen is replaced by a \\xce\\xb1-monofluoromethylene moiety. 2009 Elsevier Ltd. All rights reserved.", "id": 877} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit exhibits broad bioactivity including inducing apoptosis of scar cells and anti - inflammatory and anticancer [ 3 , 4 ] properties , which have been used in the traditional chinese medicine for treatment of hypertrophic scar , inflammation , cancer , and other diseases without obvious toxicity or side effect in clinic .\nseveral preparions , hydrogel , lotion , injection , and liposome , for example , have been reported in the literature .\nwe are further interested in the form of liquid crystalline nanoparticles ( cubosome ) , for cubosome consists of a curved bicontinuous lipid bilayer extending in three dimensions and separating two congruent networks of water channels [ 911 ] , which can enclose hydrophilic , amphiphilic , and hydrophobic substances ranging from low - molecular - weight drugs to proteins , peptides , amino acids , and nucleic acids .\ncompared to liposomes , cubosomes showed better storing stability at room temperature and could endure heat treatment [ 1315 ] .\ncubosomes could exist at almost any dilution level in water and drug leakage was less concerned compared with liposome .\nreported that cubosomes had a higher permeability coefficient ( 4.5-fold ) compared to eye drops when dexamethasone was used as a model drug .\ntherefore , we consider that the cubosome might represent a promising vehicle containing matrine for effective ocular drug delivery .\nhplc , lc / ms / ms , and esi - qtof - ms / ms methods have been used to determine matrine in samples at present [ 6 , 17 , 18 ] .\nthe aim of this study is to establish and validate a simple , sensitive , and accurate hplc method to determine matrine combined in liquid crystalline nanoparticles .\nglycerol monooleate ( dimodan mo / d kosher , material number 116703 ) was kindly provided by danisco cultor ( brabrand , denmark ) and used as received .\npoloxamer 407 ( peo98pop67peo98 ) was a gift from basf ( ludwigshafen , germany ) .\nmilli - q - grade water purified through a millipore system ( elga labwater , sartorius , uk ) was used throughout this study .\npbs ( ph 6.8 ) was made according to the chinese pharmacopoeia ( 2010 ) .\nliquid crystal nanoparticles were prepared through the fragmentation of glycerol monooleate / poloxamer 407 bulk cubic gels .\nglycerol monooleate ( 3 g ) and poloxamer 407 ( 300 mg ) were first melted at 60c in a hot water bath until they were homogeneous , after which matrine was added to dissolve / blend under continuous stirring .\nwater ( 6.7 ml ) was then added gradually and the mixture was vortex - mixed to achieve a homogeneous state .\nafter equilibration for 48 hours at room temperature , the cubic phase gel was formed . by adding 20 ml of water , the cubic gel was disrupted by mechanical stirring .\nsubsequently , the crude dispersion was fragmented for 10 min by intermittent probe sonication ( jy-96 iin , ningbo scientz biotechology co. , ltd , china ) at 200 w energy input using a pulse mode ( 9-second pulses interrupted by 18-second breaks ) under cooling in a 20c water bath .\nthe resulting milky coarse dispersion was homogenized using a high - pressure homogenizer ( avestin em - c3 , ottawa , canada ) at certain high pressures and cycles to obtain an opalescent dispersion of the cubic nanoparticles .\nthe final dispersion of liquid crystal nanoparticles was stored at room temperature for further studies .\nthe hplc analysis was carried out using a shimadzu system that is equipped with an lc-20at pump , spd-20a uv / vis detector connected to shimadzu spin chrome software .\nthe chromatographic assay was performed on a reversed - phase ods - bp c18 column ( 5 m , 4.6 mm 250 mm ) at ambient temperature 25c .\nthe mobile phase under isocratic mode was a mixture of methanol - pbs ( ph 6.8)-triethylamine ( 50 : 50 : 0.1% , v / v ) .\nthe mobile phase was degassed by an ultrasonic bath and filtered with 0.45 m membrane under vacuum .\nall the calculations concerning the quantitative analysis were carried out by an external standard method based on peak areas . to prepare the stock solution , matrine ( 10 mg )\nwas accurately weighed into 50 ml volumetric flask , made up to volume with methanol , and then the volume was adjusted to 50 ml .\nthis solution was further diluted with methanol to yield solutions containing 100.0 , 50.0 , 25.0 , 12.5 , 6.3 , 3.1 , and 1.6 g / ml . the chromatogram peak area of each known concentration was calculated .\nresults from each analysis were subjected to regression analysis . 0.2 ml ( or 200.0 mg ) of the nanoparticles\nwas accurately transferred into a 10 ml volumetric flask , dissolved , and made up to volume with methanol .\nthen , the sample solutions were filtered using a 0.45 m filter membrane and injected ( 10 l ) into the hplc system three times under optimized chromatographic conditions .\nthe method was validated in terms of parameters of specificity , linearity , sensitivity , accuracy , precision , and reproducibility according to the international conference on harmonisation .\nthe specificity of the method was assessed by comparing chromatograms of matrine working solution , blank excipients sample without matrine , and equal concentrations samples of compound liquid crystalline nanoparticles made as the previous procedure .\nthe linearity of the method was studied by injecting seven known concentrations of the standard in the range of 1.6200 g / ml .\nthe sensitivity of the method was evaluated with limit of detection ( lod ) and limit of quantification ( loq ) .\nlod and loq were established at a signal - to - noise ratio ( s / n ) of 3 and 10 , respectively .\nthe accuracy of the method was tested by comparing the percent analyte recovered by the optimum method at three concentration levels ( 80.0 , 100 , and 120.0 g / ml ) .\nintraday precision was determined by injection of standard solutions of matrine at 3 concentration levels ( 50 , 25 , and 12.5 g / ml ) , on the same day .\nthe specificity was evaluated by analyzing blank excipients sample , matrine standard solution , and liquid crystalline nanoparticles samples .\nthe retention times of matrine at a flow rate of 1.0 ml / min was 16.3 min .\nthe calibration curves for matrine were found to be linear within the range of 1.6 to 200.0 g / ml . the regression equation was y = 10706x 2959 ( r = 1.0 ) , where y is peak area and x is the concentration ( g / ml ) of matrine standard solution .\nthe correlation coefficient indicated a good linear relationship between peak area and concentration over a wide range .\nthe lod ( signal / noise ratio of 3 : 1 ) was calculated as 1.3 10 g / ml and the loq ( signal / noise ratio of 10 : 1 ) was determined as 3.9 10 g / ml .\nmean recovery for matrine at three concentration levels ( 80.0 , 100 , and 120.0 g / ml ) was found to be 102.1 1.9% ( rsd = 1.96% , n = 3 ) , 102.6 1.9% ( rsd = 2.94% , n = 3 ) , 100.5 2.1% ( rsd = 2.12% , n = 3 ) , respectively .\nthe mean concentration was 9.5 mg / ml ( rsd = 1.4% , n = 3 ) .\nseveral mobile phase systems including methanol - water , ethanol - wate - kh2po4 , and acetonitrile - ethanol - h3po4 systems have been tested in this study .\nhowever , the chromatogram of standard matrine might disappear or appear in a wide range with inaccurate calculation area ( see figure 2 ) .\nmatrine crystalline has 4 forms , namely , , , , and matrine .\nthe incorrect mobile phase may change the matrine solution to nanocrystalline because of the solubility .\nthe chromatographic method was eventually carried out using an isocratic system with a mobile phase of methanol - pbs ( ph 6.8)-triethylamine ( 50 : 50 : 0.1% ) applied at a flow rate of 1 ml / min with detection wavelength at 220 nm . under these optimum mobile phase conditions ,\nelution of analyte was completed in less than 20.0 min and retention time of matrine was 16.3 min .\nthe method was validated according to ich guidelines with the parameters of specificity , linearity , sensitivity , accuracy , precision , and reproducibility .\na simple , rapid , selective , and sensitive hplc method has been developed and validated for the determination of matrine when formulated in cubosome particles .\nthe present study is the first report on the matrine determination combined with particle dispersion system .\nthe method can be used for controlling the quality of the cubosome and helpful for further investigation .", "answer": "a reversed - phase high - performance liquid chromatographic method has been developed to quantitatively determine matrine in liquid crystal nanoparticles . \n the chromatographic method is carried out using an isocratic system . \n the mobile phase was composed of methanol - pbs(ph6.8)-triethylamine ( 50 : 50 : 0.1% ) with a flow rate of 1 ml / min with spd-20a uv / vis detector and the detection wavelength was at 220 nm . \n the linearity of matrine is in the range of 1.6 to 200.0 g / ml . the regression equation is y = 10706x 2959 ( r2 = 1.0 ) . \n the average recovery is 101.7% ; rsd = 2.22% ( n = 9 ) . \n this method provides a simple and accurate strategy to determine matrine in liquid crystalline nanoparticle .", "id": 878} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npatients with cervical radiculopathy due to single - level degenerative disc disease who fail to improve with nonoperative therapy are candidates for anterior decompression and reconstruction with either an arthrodesis or arthroplasty .\nboth procedures require minimal hospitalization and are highly effective in relieving pain and improving neurological function .\nthe ability to return to work and the speed with which this occurs are important to the individual being treated and also to society .\narthrodesis and arthroplasty differ in that one treatment eliminates motion at a cervical spinal segment while the other preserves it .\nthis fundamental difference may impact postoperative function in terms of activity level , which ultimately could facilitate or hinder the ability to return to work .\nin patients with degenerative disease of the cervical spine , does cervical artificial disc replacement lead to better work - related outcomes than fusion ? does return to work after surgery differ based on gender , age , smoking , litigation status , workers compensation status , or other sociodemographic factors ? study design : systematic review .\ninclusion criteria : studies ( coe i - ii ) directly comparing cervical artificial disc replacement ( c - adr ) with discectomy and fusion ( anterior cervical discectomy and fusion [ acdf ] ) in patients with degenerative cervical disc disease ; us food and drug administration ( fda)-approved or unapproved devices in phase iii trials with 1 year of follow - up data in a peer - reviewed journal ; subanalysis data from fda investigational device exemption ( ide ) trials .\nexclusion criteria : studies in patients with disc replacement or fusion in the thoracic or lumbar spine . outcomes :\nproportion of patients working at follow - up ; time to return to work following surgery .\nanalysis : proportion of patients working and mean or median number of days until return to work were abstracted from the reports as available . pooling of data was not done due to concerns regarding heterogeneity and the lack of well - defined measures of return to work .\ninclusion criteria : studies ( coe i - ii ) directly comparing cervical artificial disc replacement ( c - adr ) with discectomy and fusion ( anterior cervical discectomy and fusion [ acdf ] ) in patients with degenerative cervical disc disease ; us food and drug administration ( fda)-approved or unapproved devices in phase iii trials with 1 year of follow - up data in a peer - reviewed journal ; subanalysis data from fda investigational device exemption ( ide ) trials .\nexclusion criteria : studies in patients with disc replacement or fusion in the thoracic or lumbar spine .\noutcomes : proportion of patients working at follow - up ; time to return to work following surgery .\nanalysis : proportion of patients working and mean or median number of days until return to work were abstracted from the reports as available .\npooling of data was not done due to concerns regarding heterogeneity and the lack of well - defined measures of return to work .\nwe identified eight reports that met our inclusion criteria , which included information on return to work . from a total of 295 citations retrieved ,\n1 ) . of these , eight met the inclusion criteria , four of which described the same study at different follow - up points ( table 1 ) .\nseven article representing four randomized controlled trials ( coe ii ) and four artificial discs are critically summarized : bryan cervical disc : us1,2 and china,3 prestige st,4,5 prodisc - c,6 and kineflex|c.7 in addition , we summarized a secondary analysis of data from the u. bryan and prestige rcts that focused on a subset of patients who were covered by workers compensation.8 further details on the class of evidence rating and additional data for these studies can be found in the web appendix at www.aospine.org/ebsj .\npercentage of patients working at follow - up ( \n tables 2,3 ) in two studies,2,4 the overall proportion of patients who were working increased postoperatively approximately 10%12% ( from 65% preoperatively to 75% at 24 months ) .\nlarger improvements were evident among workers compensation patients ( from 36%63%),8 and a third study6 reported no preoperative or postoperative differences in work status . at 24 months\npostoperatively , there was no significant difference in work status between disc replacement and fusion patients across three trials .\nwork status less than 24 months after surgery was reported in only one study,2 and suggested that disc replacement patients were more likely than fusion patients to be working 6 weeks after surgery .\nthis difference was more pronounced in workers compensation patients.8 patients covered by workers compensation appeared to be less likely to be working at all time points ; however , no direct statistical comparisons of these patients - to - patients with other insurance were reported .\n2 ) patients who received disc replacement began working sooner after surgery than patients who received fusion with statistical significance reported in two studies .\nafter controlling for gender , study , and preoperative work status , the difference between treatments for median time to work return among worker s compensation participants did not reach statistical significance . among patients who were covered by workers compensation , those who were working at the time of surgery returned to work sooner than did patients in the full sample of the worker s compensation patients .\nno direct comparison of workmen s compensation patients - to - other patients was reported .\ndifferential effects of c - adr / acdf on return to work \n no studies examined differential work - related outcomes by gender , smoking status , litigation , or any characteristic other than workers compensation .\nno direct comparisons of worker s compensation patients - to - patients with other insurance were possible .\nthe pattern of findings for workers compensation patients , however , was similar to that of patients in general : earlier return to work with disc replacement compared with fusion and no significant group differences in work status after 6 months .\none study 7 reported that the proportion of patients who rated their activity level as \nrct indicates randomized controlled trial ; nr , not reported ; and n / a , not applicable .\nc - adr indicates total disc replacement ; acdf , anterior cervical discectomy and fusion ; wc , workers compensation ; and nr , not reported .\nc - adr indicates total disc replacement ; acdf , anterior cervical discectomy and fusion . * workers compensation patients only ; controlling for gender , study , and preoperative work status . \nthis analysis of the data demonstrated that patients treated with disc replacement tended to return to work more quickly than those receiving fusion , but that overall return to work in the two groups was equivalent at 2 years .\nboth therapies have been shown to be safe and effective ; therefore , it is expected that most patients will be able to resume normal productive lives .\nthe c - adr patients tended to return to work sooner than fusion patients and the reasons for this are unclear .\nthe first is either patient or surgeon bias since neither group was blinded . at the time of enrollment for each of the studies ,\nc - adr had not been approved in the united states , and it could be presumed that the primary patient motivation to enter one of the studies was to obtain a c - adr .\nthis high level of interest could have led to a placebo effect in those receiving the c - adr .\nadditionally , surgeons may have been more willing to release patients to work if they received a c - adr .\nfinally , it may be that there is period during which the patient adjusts to the loss of a motion segment which is associated with increased discomfort , particularly with activity .\nsuch an adjustment would not occur with c - adr and if real , could account for the difference in early return to work .\nconclusions from this review are limited by the following : follow - up rates in the prestige study were low ; however , these low rates were due to the publication of articles before all patients had reached the follow - up window .\nfollow - up rates at 4 years were also fairly low ( 75% ) in the fda bryan trial ; however , in both of these studies loss to follow - up was equivalent across treatment groups .\nquestions about return to work were assessed with patient self - report and apparently not validated with work records .\nno definition was provided of self - reported return to work ( eg , how the question was asked , whether part - time work was included ) .\nthe measures do not reflect return to work per se , as return to work assumes that patients were working before surgery .\nthe proportions of people who are working do not reflect individual change from preoperative to postoperative , only group percentages at the various time points .\nthese percentages were not broken down by the work status of the patient before surgery , and included patients who were working postoperatively as well as those who were not working .\ntherefore , this measure does not accurately reflect return to work but rather work status at the time of follow - up in the study population .\nno direct comparison of patients with workers compensation versus patients with other kinds of insurance was reported in a secondary analysis of the bryan and prestige trials .\nworkers compensation patients comprised only about 10% of patients in those two trials , so that it is likely that the percentages reported in table 2 for the full sample would be close to the percentages for the nonworkers compensation sample .\nif that is the case , then indirect comparisons of the workers compensation patients with the full sample would approximate differences between patients with and without workers compensation .\nonly the published articles from the bryan trial1,2 provided data on working status less than 2 years after surgery\n. measures from earlier time points were collected in the prestige trial and analyzed by steinmetz et al,8 but they are not reported in the main articles from the prestige study.4,5\ndisc replacement patients were more likely than fusion patients to be working at 6 weeks postoperatively in one study no significant differences between treatment groups in proportion of patients working after 6 months of follow - up in three rcts earlier return to work following surgery for disc replacement than for fusion across three rcts ; statistically significant differences were seen in two studies one study reported equivalent activity levels at 24 months in both treatment groups", "answer": "study design : comparative effectiveness review.study rationale : the ability of a patient to return to work and the speed with which this occurs are important outcome metrics for the assessment of patients undergoing spinal surgery.clinical questions : in patients with degenerative disease of the cervical spine , does cervical artificial disc replacement ( c - adr ) lead to better work - related outcomes than fusion ? does return to work after surgery differ based on gender , age , smoking , litigation status , workers compensation status , or other sociodemographic factors?methods : a systematic search and review of the english - language literature was undertaken to identify studies published through october 2 , 2011 . \n pubmed , cochrane , national guideline clearinghouse databases , and bibliographies of key articles were searched . \n two individuals independently reviewed articles based on inclusion and exclusion criteria , which were set a priori . \n each article was evaluated using a predefined quality - rating scheme.results : for follow - up periods of more than 6 months , there was no significant difference in work status between disc replacement and fusion patients ; however , c - adr patients began working sooner after surgery . \n statistical significance for earlier return was not reached in all studies.conclusions : most patients undergoing cervical decompression and fusion or c - adr return to work . \n the rates are equivalent at 6 months but patients treated with c - adr resumed work sooner .", "id": 879} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na large increase in fusion rates for spine surgery has been observed in the last 20 years9 ) , and the frequency of revision spine surgery continues to increase .\nthe most common reasons for additional surgery7 ) following fusion surgery are implant complications and pseudoarthrosis .\n. they may be in the shape of a male or female rectangle or hexagonal , octagonal , or star - shaped .\ntherefore , it is necessary to have the instrument set used during the first operation or to have an appropriate screwdriver available .\nthis is not always possible and in some circumstances the implant may no longer be in production . when revision surgery studies were examined5,12 ) ,\nmethods to remove broken screws are reported but very little information related to removing normal screws has been provided .\nno previous report has described a single - piece screw remover to remove normal screws . a small part of the rod is cut and placed in the screw when a removal set is not available . after tightening the screw head , mobile screw 's head\nthis screw is a single piece that can be removed by hand or with pincers10 ) .\nthe polyaxial remover presented here requires only a cap - screw screwdriver to remove the polyaxial screws .\ndue to the structure of the remover and the method , existing screws can be removed with minimal dissection of surrounding soft tissue .\ndebridement is important to remove scars , envision the bone elements , and prepare a new fusion bed during revision surgery .\nadditional procedures applied to remove screws cause the surgeon to expend extra effort , which may lead to loss of time .\nour tool simplifies and accelerates the screw removal process ; thus , shortening operating time .\nthe aim of our polyaxial screw remover design is to facilitate screw removal and thereby reduce blood loss , infection risk , cost , and effort expended by the surgeon .\nthe patient demographic data and reasons for primary and revision surgery are given in table 1 .\nthe aim when removing polyaxial screws is to stabilize the polyaxial head so the screw becomes monoaxial and can be removed by turning .\nthe method described by kose et al.6 ) was of benefit when we designed our instrument , which has not been described previously in the literature . in the method of kose\net al . , the screw becomes monoaxial with a rod and cap screw , whereas we used a u - shaped end section in our instrument without the need for a rod .\nthe polyaxial remover consists of a single - piece shaft , sleeve , and handle ( fig .\nthe shaft section is hollow , and the screw cap is tightened with a screwdriver .\nthus , a spine screw enters easily , and the surgeon avoids damaging surrounding tissue .\nthe head section of a polyaxial screw was removed , and the screw was placed in the u - section ( fig .\nthe cap screw was tightened on the screw , and the screw was fixed in the end section of the apparatus .\nthe polyaxial screw that became monoaxial can be removed by turning the handles on the shaft .\nthis method also removes the need to clean the fibrous tissue covering the internal screws and to see the screw shape .\na total of 42 polyaxial screws were removed from five patients with the new single - piece screw remover ( fig .\nthe polyaxial cap screws were 4.5 hexagonal screws in four patients and star - shaped in one patient .\nafter removing the cap screws and rods , all of the polyaxial screws were made monoaxial with the instrument described above and were removed rapidly in a minimally invasive way with no complications .\nwe have described a screw removal instrument designed to overcome the problems of screw removal often encountered during revision surgery .\nour clinical application shows that these screws can be removed without the need for additional materials or soft tissue debridement within or below the screw head .\nthe correct screwdriver for the materials used can not always be obtained to remove existing implants during revision surgery because of the different designs .\nthis explains why revision surgery can be a longer and more fatiguing operation with increased blood loss .\nof the several known spine surgery problems , the most accepted and most widely used method for repair is pedicle screw fixation1,2,3,4,5,6,7,8,9,10,11 ) .\nafter fixation , the most common reasons for revision surgery7 ) are implant problems and pseudoarthrosis .\nmethods and instruments to remove broken screws have been described in the literature5,12 ) . however , no additional methods6,10 ) , other than the rod techniques for removing normal screws , have been described . in the u - rod technique described by kse\net al.6 ) , the cap screws are removed with an allen key , and the screw is placed in the u - shaped rod after removing the rods . after tightening the screw head , the screw with a mobile head becomes a monoblock screw . this single - structure screw can be removed by hand or with pincers .\nin addition , large metal cutters are required to cut the rods , a rod bender is needed to shape , and pincers are needed to turn the rod placed on the screw head .\nour screw remover design is a single piece and will not damage surrounding tissue or the pedicle ( fig .\nthere is no need for metal cutters or a rod bender ; thus , reducing the time and effort required .\nthe tool also removes the need to clean the fibrous tissue covering the internal screws to determine screw shape .\nsecond , a polyaxial remover was used after removing the cap screws , so it was necessary to have a screwdriver suitable for the cap screws\n. however , cap screws are generally hexagonal or star - shaped and there are few varieties .\nthese screws are generally found in sets , or the screwdriver in the revision set can be used .\nanother limitation was that the polyaxial remover could not be used if the cap screw is damaged or broken .\nthe screw removal technique using the polyaxial remover is practical and easy and requires a minimal amount of time .\nthe instrument described here can be used to remove all types of polyaxial and monoaxial screws used in spine surgery .\nhere is no requirement for additional screw removal tools or materials and unnecessary debridement is avoided .", "answer": "objectiveto present the clinical benefits of an instrument designed to facilitate removal of polyaxial screws during revision surgery.methodsall polyaxial screws can be removed without additional materials or a large amount of debridement using our newly designed instrument . \n forty - two screws were removed from five patients without any complications using this instrument.resultswe removed the cap screws and rods from the 42 polyaxial screws in five patients and made them monoaxial using the new screw removal apparatus . \n the screws and rods were removed quickly in a minimally invasive way with no complications . no damage to the pedicle or surrounding soft tissue occurred during screw removal . \n no neurogenic changes developed during revision surgery after changing the screws.conclusionthis newly designed screw removal instrument was used safely and effectively to remove all polyaxial and monoaxial pedicle screws .", "id": 880} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalopecias can be broadly classified into non - scarring or non - cicatricial and scarring or cicatricial forms .\npathologically , a scar constitutes the end point of reparative fibrosis with permanent destruction of the preexisting tissue.1 scarring alopecias are further subdivided into primary and secondary types . in primary scarring alopecias ,\nthe hair follicle is the primary target of destruction , which is microscopically evident as preferential destruction of follicular epithelium and/or its associated advential dermis with relative sparing of the reticular dermis.2 this group includes the following clinical entities : chronic cutaneous lupus erythematosus ( ccle ) , lichen planopilaris ( lpp ) , pseudopelade of brocq ( pb ) , folliculitis decalvans ( fd ) , dissecting cellulitis / folliculitis ( df ) . if the follicular destruction is secondary to the scarring and occurs outside the follicular unit , e.g. , the reticular dermis , epidermis , or sub cutis , it can eventually impinge upon and even eradicate the whole follicle .\nthe term secondary scarring alopecia implies that follicular destruction is not the primary pathologic event .\nexogenous factors , such as burns , and endogenous infiltrative and inflammatory diseases , such as sarcoidosis , pemphigus vulgaris and reticular dermal sclerosis , can result in secondary alopecias . in 2001 ,\na group of hair clinicians , pathologists and researchers , under the rubric of the north american hair research society ( nahrs),3 issued a consensus opinion on the classification of primary cicatricial alopecias . the proposed classification subdivides primary scarring alopecias on the basis of the predominant type of inflammatory cell component , an approach that had already published1,4,57 and was further refined by the workshop .\nin addition to the lymphocyte- and neutrophil - associated subgroups , a mixed and nonspecific group was differentiated and newly defined ( table 1 ) . in the late phase of cicatricial alopecias ,\na histopathologic diagnosis is more difficult because the main criteria of classification , i.e. , the type of inflammatory infiltrate , can not always be evaluated . in these cases , additional criteria , such as the evaluation of the perifollicular elastic sheet and the fibrosis ,\nthe goal of this study was to review clinical and histopathologic findings of 38 patients diagnosed with late , pauci or non - inflammatory phase of cicatricial alopecias at the dermatologic department of the hospital das clinicas , so paulo university medical school , over a six - year period in order to classify them by sub - types according to nahrs and evaluate the dermal elastic system and thickness of the epidermal basement membrane , using weigert and pas stains , respectively .\nbiopsy specimens obtained using 5-mm punches from patients seen between 2000 and 2005 at the dermatologic department of hospital das clinicas , so paulo university medical school with cicatricial alopecias in the late , pauci or non - inflammatory phase were reevaluted .\nessential criteria included histopathologic diagnosis of cicatricial alopecia and accessibility of the patient s clinical records .\nslides stained with hematoxylin and eosin , pas and stain for elastic tissues ( weigert with previous oxidation by peracetic acid ) were reviewed , evaluating the presence or absence of criteria listed in the table 2 .\na total of 38 cases with a histopathologic diagnosis of cicatricial alopecia were included in the study .\nthese cases had been previously diagnosed as follows : eight cases of ccle , two cases of lpp , 13 cases of pb , two cases of fd , one case of scleroderma and 13 cases of non - specific cicatricial alopecia .\ntwelve of 13 cases ( 92.3% ) that were initially classified as non - specific cicatricial alopecias could be specifically reclassified .\nchronic cutaneous lupus erythematosus was diagnosed in 17 cases , representing 43.6% of the total number of scarring alopecias .\nthe female to male ratio was 4.7 : 1 ( 14 females and three males ) .\nthe age at onset ranged from 29 to 75 years , with a mean age of 46.5 years .\ncharacteristic histopathologic findings of the late phase included hyperkeratosis , horn plugs , atrophy of the malpighian layer , slight vacuolar degeneration of the basal layer , and fibrous tract replacing the follicles .\na thickened basal membrane could be seen in 58.8% of the cases on pas stained sections , and an incomplete elastic sheet occurred around the fibrous tracts . in all cases on weigert- stained sections .\nelastolytic foci were also found in areas of fibrosis outside the perifollicular zone ( figure 1d f ) .\nthis category of cicatricial alopecia represented 10.2% of the total number of biopsies , totaling four cases .\nin one case , there was a lichenoid infiltrate around the infundibuloisthmic segment of one follicle in addition to fibrous tracts replacing follicles .\nin all the others , absence of inflammation , absence of sebaceous epithelium , and atrophy of the bulge area occurred , resulting in hourglass figures .\nfibrous tracts replacing the follicle , with or without the presence of colloid bodies , were also observed .\nthe basal membrane was not thickened on pas - stained sections , and the perifollicular elastic sheet was partially destroyed , as observed with the weigert stain ( figure 1g \npseudopelade of brocq was diagnosed in 12 cases , representing 30.8% of the total number of biopsies .\nage of onset ranged from 23 to 69 years , with a mean age of 54.4 years .\ncharacteristic histopathologic findings were the absence of criteria seen in ccle and lpp and preservation of the elastic sheet around the follicles ( figure 1a c ) .\nfolliculitis decalvans was diagnosed in three cases , representing 7.7% of the total number of biopsies .\nthe histopathologic hallmark was the presence of superficial suppurative folliculitis and fibrosis replacing the follicle and the perifollicular area , with elastolysis visible with the weigert stain ( figure 2a c ) .\nthis category of cicatricial alopecia represented 2.6% of the total number of cicatrizing biopsies , totaling one case in a female 19 year - old patient . in this case , the inflammation was slight , and there was an extensive and deeper dermal fibrosis extending to the hypodermis , with elastolysis ( figure 2d f ) .\none case of non - specific alopecia was diagnosed due to the destruction of the follicles being the only histopathologic finding .\nthis category of cicatricial alopecia represented 10.2% of the total number of biopsies , totaling four cases .\nin one case , there was a lichenoid infiltrate around the infundibuloisthmic segment of one follicle in addition to fibrous tracts replacing follicles .\nin all the others , absence of inflammation , absence of sebaceous epithelium , and atrophy of the bulge area occurred , resulting in hourglass figures .\nfibrous tracts replacing the follicle , with or without the presence of colloid bodies , were also observed .\nthe basal membrane was not thickened on pas - stained sections , and the perifollicular elastic sheet was partially destroyed , as observed with the weigert stain ( figure 1g \npseudopelade of brocq was diagnosed in 12 cases , representing 30.8% of the total number of biopsies .\nage of onset ranged from 23 to 69 years , with a mean age of 54.4 years .\ncharacteristic histopathologic findings were the absence of criteria seen in ccle and lpp and preservation of the elastic sheet around the follicles ( figure 1a c ) .\nfolliculitis decalvans was diagnosed in three cases , representing 7.7% of the total number of biopsies .\nthe histopathologic hallmark was the presence of superficial suppurative folliculitis and fibrosis replacing the follicle and the perifollicular area , with elastolysis visible with the weigert stain ( figure 2a c ) .\nthis category of cicatricial alopecia represented 2.6% of the total number of cicatrizing biopsies , totaling one case in a female 19 year - old patient . in this case , the inflammation was slight , and there was an extensive and deeper dermal fibrosis extending to the hypodermis , with elastolysis ( figure 2d f ) .\none case of non - specific alopecia was diagnosed due to the destruction of the follicles being the only histopathologic finding .\nconsidering the group of primary lymphocytic cicatricial alopecias in the inflammatory phase , a differential diagnostic consideration for ccle is lpp .\nthe superficial and deep perivascular and periecrine patterns of inflammation further aid in differentiating ccle from lpp . in the late pauci or non - inflammatory phase , as observed in our cases of ccle , interfollicular epidermis alterations were evident ( hyperkeratosis and atrophy ) , in an area usually spared in lpp cases .\ncommonly , in the dermis in lpp , the only disturbance was the fibrous tract replacing the follicle , while in ccle , there was frequent extra follicular fibrosis and elastolysis ; even in this late phase , the basement membrane was thickened in 58.8% of cases .\nccle is differentiated from pb by the presence of predominately vacuolar interface changes at the level of follicular infundibulum in the former and lack of interface alterations in the latter.1 in our cases , the perifollicular elastic sheet was preserved in pb cases , while it was partially destroyed in lpp and ccle , confirming the previous findings of pinkus et al.7 some authors believe that pb is not a distinct clinical - pathologic entity but a variant of certain primary cicatricial alopecias or , alternatively , a form of end - stage alopecia caused by other scarring alopecias , such as ccle , lpp and fd.79 according to stephen ( 1993)1 and other authors , with whom we agree , pb does indeed have sufficient distinct pathologic features to merit a separate classification.5,1012 klaus and wilma ( 2006)1 believe that the close clinicopathlogic correlation in the histologic absence of significant follicular plugging , as well as the use of elastic fiber stain in addition to evaluation of conventional he - stained sections , should enable the differentiation of classic pb from late stage lesions of lpp and ccle in most cases and further justify the classification of the condition as an entity sui generis . in relation to the neutrophilic cicatricial alopecias ,\nit is remarkable that even in the late phases of this disorder , it seems that the inflammatory process persists in our cases , , and a neutrophilic folliculitis can frequently be seen , which helps make the correct histopathologic diagnosis .\nwe could also see that the fibrotic process that is secondary to this neutrophilic folliculitis was more intense and proceeded by a granulation tissue , as is expected after a suppurative process .\nsinus tracts are the histopathologic hallmark of dissecting cellulites and are not seen in either folliculitis decalvans or acne keloidalis and were not observed in our late phase cases .\nbacterial or fungal folliculitis ( kerion and favus ) may have to be excluded in the group of neutrophilic cicatricial alopecias , with the use of special stains .\nacne keloidalis cases were not seen in our series because they are histopathologically reported in our laboratory as a superficial and deep suppurative and giant cellular granulomatous folliculitis with extensive fibrosis compatible with acne keloidalis , not as a cicatricial alopecia .\nbesides , the clinical aspect of this disorder is so typical that histopathologic exam is seldom required .\na scalp biopsy is mandatory in all cases of cicatricial alopecias , representing the clinically inflammatory area .\nif there is no evidence of inflammation , a biopsy at the border of the cicatricial zone should be performed .\na precise diagnosis is possible , even in the late , pauci or non - inflammatory phase of cicatricial alopecias if a systematic evaluation of a constellation of criteria is employed , using routine he , pas and a stain for elastic tissue . in our cases , this method allowed a precise diagnosis in 97.4% of cases , even in those initially considered non - specific cicatricial alopecia .", "answer": "backgroundscarring alopecias are classified into primary and secondary types according to the initial site of inflammation . in primary scarring alopecias , the hair follicle is the main target of destruction ; the term secondary cicatricial alopecia implies that follicular destruction is not the primary pathologic event.aimsto review the histopathologic diagnoses of cases of cicatricial alopecia in order to classify them according to the north american hair research society.patients and methodspatients with biopsy specimens diagnosed as cicatricial alopecia seen from 2000 to 2005 at the dermatologic department of hospital das clinicas , so paulo university medical school had hematoxylin and eosin , periodic acid - schiff and weigert stained slides reevaluated and sub - typed into different primary cicatricial alopecias.resultsthirty-eight cases of primary cicatricial alopecias were reclassified as : chronic cutaneous lupus ( 17 ) , lichen planus pilaris ( 4 ) , pseudopelade of brocq ( 12 ) , folliculitis decalvans ( 3 ) , dissecting folliculitis ( 1 ) , and non - specific scarring alopecia ( 1 ) . in our cases , the methods employed allowed an accurate diagnosis in 12 of 13 cases ( 92.3% ) previously classified as non - specific cicatricial alopecias.conclusionseven in the late , pauci or non - inflammatory phases , an approach with systematic evaluation of a constellation of criteria in routine hematoxylin and eosin stain , periodic acid - schiff and weigert stain allowed for a more accurate diagnosis of cicatricial alopecias .", "id": 881} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npectus excavatum ( pe ) , characterized by posterior displacement of the sternum and cartilaginous - rib attachments , is one of the most common congenital chest wall deformities.1)2 ) the physiological impact of pe varies .\nsymptomatic patients frequently complain of dyspnea with exertion , progressive loss of endurance , tachycardia , palpitations and chest discomfort.3 - 5 ) in a critical location , even small depressions of the chest can create significant cardiac dysfunction when the right heart and pulmonary outflow tract are compressed to varying degrees by the depressed sternum.5 - 7 ) an index of severity can be calculated by measuring the inner width of the chest ( at the lowest level of the pectus defect ) and dividing it by the distance between the posterior surface of the sternum ( at the lowest part of the defect ) and the anterior surface of the spine ( with normal being approximately 2.52).2)3 ) in general , an index of 3.2 or greater is considered severe however symptoms do not necessarily correlate with severity of index.2 - 4 ) echocardiography plays a significant role in the evaluation of patients with pe .\nthe degree of right heart compression however is often difficult to assess by transthoracic echo ( tte ) especially with severe deformities that prevent the operator from obtaining the normal transthoracic views.7 - 9 )\na 32-year - old woman presented to out - patient clinic for further evaluation of a 1-year history of progressive chest pain , fatigue , dizziness , paroxysmal tachycardia and dyspnea with exertion . with even mild exertional effort she experienced sharp , \" stabbing \" chest pain along the left lower and mid - sternum .\na 12-lead electrocardiogram demonstrated a right - bundle branch block with left posterior fascicular block .\nshe had a history of severe pe ( index of > 4 ) for which she had undergone operative repair 18 months prior by an open resection of cartilage attachments and sternal \" flip \" as described by hawkins & colleagues.10 ) prior to her first correction , she had some dyspnea with exertion , however , cardiac work - up , including echocardiogram had been reported to not show any abnormalities .\nshe noted onset of her current symptoms approximately 6 months after her pe repair . a subsequent operation with superficial anterior remodeling of the chest wall cartilage on the left side of the sternum had failed to relieve her progression of pain and symptoms .\nshe exhibited post - operative abnormal remodeling of the chest wall with residual as well as some recurrent pe .\nthe sternum protruded anterior with bilateral depression of the costal - sternal attachments creating a \" wave - like \" appearance ( fig .\nclose attention to the anteroposterior planes ( best seen from the apical four - chamber views ) clearly demonstrated extrinsic compression and deformation of the lower mid - right ventricle ( rv ) by the chest wall which is more obvious during diastole ( fig .\n3b ) . biplane and live 3-d images of the preoperative transesophageal echocardiogram ( tee ) improved the visualization and localization of extrinsic compression of the right ventricle ( fig .\ntricuspid valve prolapse is seen likely due to partial compression of the rv resulting in distortion of the tricuspid annulus ( fig .\nopen revision of her chest wall deformity was performed with placement of two stainless steel support bars ( lorentz surgical , jacksonville , fl , usa ) and a trabecular metal implant ( zimmer , inc . ,\nminneapolis , mn , usa ) which elevated the sternum and depressed regions 3 - 4 centimeters anterior to the rv with good cosmetic results ( fig .\nsymptomatic pe patients often present for cardiovascular evaluation with tte being the most commonly utilized diagnostic modality .\ndocumenting the effects of a depressed chest wall on the right heart and outflow tract as well as any associated interference with diastolic filling is critical for decision making in patient treatment and the need for potential surgical intervention .\nmodifying standard views such as biplane transthoracic and transesophageal views may be necessary in some patients due to limitations from the abnormal anatomy of the deformed anterior chest wall . in some cases , rv compression is often difficult to assess by tte especially with severe deformities that prevent the operator from obtaining the normal transthoracic window views .\ntechnical tips for assessment of the rv include 1 ) narrowing the 2-d sector width to optimize only rv structures ; 2 ) use of harmonic imaging and adjustment of gain and compression for good contrast and endocrinal edge detection ; 3 ) making all measurements at end - diastole or the frame demonstrating the largest chamber dimension ; and 4 ) for 2-d measurements , obtain all acquisitions during quiet respiration or full - expiration .\napical four - chamber views when seen clearly can usually visualize any extrinsic compression to the rv of the heart .\nuse of all three possible traditional acoustic windows ( parasternal short - axis , apical and subcostal ) may be necessary . in an effort to minimize foreshortening of the rv , the transducer can be positioned down an intercostal space and laterally until the rv apex is clearly seen . in some patients\na transesophageal and transgastric view may be necessary to better evaluate the right heart chambers and rv outflow obstruction .\nmany patients with pe have associated alterations in rv morphology and function . assessment for localized sacculation of the rv wall , global dilation of the ventricle , prominent trabeculae , and/or hypertrophy of the moderator band is important . identifying abnormalities , including mitral valve prolapse and aortic root measurements are especially critical in suspected or confirmed cases of marfan syndrome .\nresolution of mitral valve prolapse with release of the chest wall entrapment is seen in more than half of patients after pe correction.7)11)12 ) more importantly , many patients improve their symptoms such as exertional dyspnea and chest pain which may be related to extrinsic compression of the rv and reduced preload.4)5)7 ) further studies are needed to better understand the pathophyiology of symptoms in relation to cardiac and chest wall function in patients with pe . in conclusion ,\nechocardiographic evaluation is critical in patients with symptomatic pe to assess the degree of rv compression .\nwe presented a case of a pe in a patient with symptoms including severe chest pain with exertion that was diagnosed with the expertise of echocardiography and subsequently surgically corrected .\nsubtle abnormalities in cardiac structure and chest wall compression may result in debilitating symptoms in a small population of patients.2 - 4 ) when astutely performed , echocardiography can accurately provide clinically relevant information about cardiac size and any hemodynamic compromise in patients with pe .", "answer": "pectus excavatum exists as varying anatomic deformities and compression of the right heart by the chest wall can lead to patient symptoms including dyspnea and chest pain with exertion . \n echocardiography can be difficult but is critical to the evaluation and diagnosis of this patient population . \n modifying standard views such as biplane transthoracic and 3-d transesophageal views may be necessary in some patients due to limitations from the abnormal anatomy of the deformed anterior chest wall . \n apical four - chamber views when seen clearly can usually visualize any extrinsic compression to the right ventricle of the heart .", "id": 882} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnsclc is the most common type of lung cancer and the most common malignant neoplasm worldwide ( 1 ) . during past decades\n, various studies have attempted to identify molecular biomarkers to predict the prognosis of nsclc ( 2 , 3 ) .\nnumerous promising biomarkers have been evaluated but none of these have been effective for clinical use ( 2 , 3 ) .\nthe main cell population in anti - cancer immune response is the population of cytotoxic t lymphocytes ( ctls ) ( 4 ) .\nthe ctls population is represented by cd8 + lymphocytes , cd4 + lymphocytes , natural killer cells ( nk ) , natural killer t cells ( nkt ) and lymphocytes b ( 5 , 6 ) .\ncancer cells are killed by induction of apoptosis by cytolytic reaction or membrane - receptor induction of programmed death .\nthe successful cytotoxic attack needs an effective antigen presentation by tumor cells and antigen presenting cells ( apc ) .\nanti - cancer defense is ineffective in clinically detectable cancers and the greater is the size of a tumor mass , the less effective anti - cancer response is ( 8) .\nlung cancer cells hide against cytotoxic attack by low antigen presentation and low co - stimulatory molecule expression .\nthe lung cancer antigens are unstable and badly defined as a result of multiple genetic and epigenetic alterations during oncogenesis ( 9 ) .\nhepatitis b ( 10 ) and inflammatory bowel disease ( 11 ) are examples , leading to hepatocellular and colorectal cancer\n. neutrophils , as a key component in inflammation , may play a crucial role in inflammation driven tumorigenesis ( 12 ) .\nneutrophils support angiogenesis via secretion of proangiogenic factors or by proteolytic activation of proangiogenic factors .\nneutrophils are implicated in tumor growth through the proteolytic release of egf - epidermal growth factor , tgf1-transforming growth factor \n1 , and pdgf platelet derived growth factors from the extracellular matrix ( ecm ) ( 13 ) .\nimmature neutrophils or g - mdsc ( granulocytic myeloid derived suppressor cells ) are implicated in the establishment of an immunosuppressive tumor microenvironment .\nneutrophils kill tumor cells through direct or antibody dependent cell cytotoxicity ( adcc ) ( 13 ) .\nthey accumulate in large numbers in premetastatic organs and have a positive effect on tumor cell seeding ( 14 - 17 ) .\nalso , it has been shown that neutrophils limit metastatic seeding by killing tumor cells ( 14 , 16 ) .\nneutrophils do not affect the growth of the metastatic nodules ( 14 , 16 ) .\nthere is a polarization of neutrophils in tumor promoting and antitumor phenotype which is mediated via cytokines in the tumor microenvironment ( i.e. tgf1 and ifns ) .\nneutrophil abundance correlates with a better prognosis in some studies and a worse prognosis in others ( 18 ) .\nplatelets play a significant role in cancer growth , progression and metastasis ( 19 , 20 ) .\nsignificant attention has been given to the association between malignancies and coagulation ( 19 , 20 ) .\na hypercoagulability is one of the signs of a more aggressive disease and thromboembolism is one of the major causes of mortality in cancer ( 21 ) .\na prognostic significance between the platelet count and lung cancer has been identified but not fully elucidated ( 22 - 27 ) .\nplatelets release some growth factors such as platelet - derived growth factor , platelet factor 4 , and thrombospondin which promote hematogenous tumor spread , tumor cell adhesion , invasion and angiogenesis and play an important role in tumor progression ( 22 , 25 - 27 ) .\nplatelets contain many active molecules and , as they adhere to sites of tumor activated or injured endothelium ; many of these molecules are released into the local microenvironment leading to platelet - mediated effects on vascular tone and neo - angiogenesis ( 22 - 27 ) .\nplatelets play important roles in the tumor microenvironment that may be thought of as a wound that never heals ( 28 ) .\nobjective of this study is to compare neutrophil / lymphocyte ratio ( nlr ) and platelet / lymphocyte ratio ( plr ) in patients with nsclc ( non- small- cell lung cancer ) with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity nsclc .\nthis is the retrospective analysis of nrl and prl in patients with nsclc at the time of the diagnosis of disease before any anti tumor treatment ( chemotherapy , radiotherapy , surgery ) .\nx 10 / l ) , calculated nlr and plr in every patient and compared obtained values in patients with metastases and patients without metastases .\nin 57 patients there were 15 males ( 26% ) mean aged 68 , 64 with metastases , 28 males ( 49% ) mean aged 64,63 years without metastases , 8 females ( 14% ) mean aged 61,63 with metastases and 6 females ( 11% ) mean aged 63,33 years without metastases .\nthere were 23 patients with nsclc ( 40% ) with metastases and 34 patients ( 60% ) without metastases .\nthe values of nlr in 34 patients without metastases were : 5,15 ; 8,57 ; 1,81 ; 1,45 ; 1,69 ; 3,77 ; 1,35 ; 1,83 ; 1,77 ; 2,11 ; 1,65 ; 2,26 ; 2,78 ; 4,25 ; 3,52 ; 1,92 ; 1,37 ; 1,77 ; 3,52 ; 1,22 ; 3,92 ; 3,28 ; 1,47 ; 3,74 ; 3,74 ; 1,82 ; 3,68 ; 2,39 ; 2,39 ; 2,67 ; 1,88 ; 1,70 ; 4,14 ; 2,84 .\nthe values of nlr in 23 patients with metastases were : 1,51 ; 13,3 ; 0,58 ; 2,25 ; 1,71 ; 3,94 ; 2,47 ; 2,97 ; 2,58 ; 2,35 ; 2,35 ; 2,01 ; 4,46 ; 4,47 ; 3,23 ; 0,78 ; 2,79 ; 2,39 ; 3,67 ; 2,23 ; 2,25 ; 6,54 ; 1,56 ; ( figure 2 ) nsclc with and without metastases in males and females nrl in patients with nsclc nlr in patients without metastases = 2.32 ( 1.75 to 3.69 ) , in patients with metastases= 2.39 ( 2,01- 3.67 ) .\nthe values of plr in 34 patients without metastases were : 221,85 ; 261,0 ; 115,34 ; 69,8 ; 130,0 ; 166,9 ; 78,93 ; 50,29 ; 105,98 ; 137,99 ; 70,77 ; 106,9 ; 178,78 ; 168,4 ; 123,7 ; 72,5 ; 150,54 ; 83,02 ; 156,46 ; 76,12 ; 184,62 ; 156,46 ; 93,85 ; 225,78 ; 225,78 ; 68,09 ; 281,58 ; 105,56 ; 105,56 ; 116,94 ; 68,46 ; 92,71 ; 328,79 ; 107,69 .\nthe values of plr in 23 patients with metastases were : 82,49 ; 402,56 ; 172,07 ; 167,60 ; 104,96 ; 220,53 ; 220,81 ; 201,15 ; 168 ; 171,65 ; 171,85 ; 133,09 ; 225,78 ; 307,84 ; 131,80 ; 204,90 ; 143,30 ; 128 ; 142,67 ; 110,90 ; 100,30 ; 124,60 ; 49,83 .\nplr in patients without metastases = 116.14 ( 81.99 to 170.99 ) , in patients with metastases=167.60 ( 124 , 60- 204.90 ) . since there was no regularity in the distribution of obtained values of nlr and plr we made the mann - whitney u test .\nmean values are not presented using the x and sd , but with a median and interquartile percentiles .\nthe nlr in patients with nsclc without metastases amounted to 2.32 ( 1.75 to 3.69 ) and was not significantly different from the nlr in patients with metastases 2.39 ( 2,01- 3.67 ) ( p=0.614 ; p = ns ) .\nthe plr in patients with nsclc without metastases amounted to 116.14 ( 81.99 to 170.99 ) and was not significantly different from the plr in patients with metastases 167.60 ( 124 , 60- 204.90 ) ( p = 0.068 ; p = ns ) .\nvarious studies have attempted to identify molecular biomarkers to predict the prognosis of nsclc ( 2 , 3 ) .\nlymphocytes , macrophages and granulocytes are involved in the anti - cancer battle ( 1 - 8 ) .\nthe main cell population in anti - cancer immune response is the population of cytotoxic t lymphocytes ( ctls ) ( 4 ) .\nneutrophil abundance correlates with a better prognosis in some studies but a worse prognosis in others ( 18 ) .\nplatelets release some tumor growth factors which play a significant role in cancer growth , progression and metastasizing ( 19 , 20 , 22 , 25 - 28 ) .\nelevated pretreatment nlr , plr and mean platelet volume ( mpv ) in peripheral blood were identified as independent prognostic factors associated with poor survival with various cancers including nsclc ( 29 ) . in 81 patients with lung cancer nlr and plr values\nwere significantly higher compared to the healthy subjects ( nlr : 4.42 vs 2.45 p=0.001 , plr : 245.1 vs 148.2 p=0.002 ) .\nno significant relationship was determined between these markers and histopathology or tnm stages ( 29 ) .\npretreatment high nlr and plr were associated with significantly shorter disease - free and survival rates in study worked on 94 patients with nsclc ; there was not impact on the response to chemoradiotherapy ( 30 ) . in 149 patients with nsclc\nnonlocal failure rates were 11% for patients with plr less than 250 and 58% for plr\n. patients with high pretreatment plr had shorter survival after stereotactic radiatiotherapy ( 31 ) .\nsome studies indicated that the combination of nlr and plr could be a better prognostic factor . in study on 366 patients in iii and iv stage of nsclc\n, patients could be divided into three prognostic groups prior to treatment : poor : nlr > 2.68 ; moderate : nlr 2.68 and plr > 119.50 ; and good : nlr 2.68 and plr 119.50 ( 32 ) .\na high pretreatment plr ( 33 ) and nlr ( 34 ) might be a predictive factor of poor prognosis in nsclc a shorter survival after treatment . some authors ( 35 )\nfailed to find the prognostic significance of nlr in nsclc and some ( 36 ) did not find correlation between plr and prognosis of nscl .\nwe compared nlr and plr in patients with nsclc without and with metastases at the time of the diagnosis of diseases .\nnrl in patients without metastases was 2.32 and plr 116.14 ; in patients with metastases nlr was 2.39 and plr 167.60 .\nalthough there was not statistical significance these results show that nlr and plr could be useful in preliminary assessment of nsclc before any treatment\n. they can be useful predictors for worse prognosis but we still do not know reference values . if our sample were grater we might be given statistical significant results .\nimmune cells and their ratio influence prognosis and that could be clinically applied in nsclc .\nmore investigations will improve the understanding of the lung cancer and may develop novel therapeutic opportunities .", "answer": "objective : to compare neutrophil / lymphocyte ratio ( nlr ) and platelet / lymphocyte ratio ( plr ) in patients with nsclc ( non- small- cell lung cancer ) : with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity nsclc.material and methods : this is the retrospective analysis of nrl and prl in patients with nsclc at the time of the diagnosis of disease before any anti tumor treatment ( chemotherapy , radiotherapy , surgery ) . \n 57 of patients with nsclc treated in the first three months of 2016 . \n year were chosen at random regardless of sex and age . \n we examined full blood count cells ( fbc ) , calculated nlr and plr in every patient and compared obtained values in patients with and patients without metastases.results:in 57 patients with nsclc there were 15 males with metastases , 28 without metastases , and 8 females with metastases , 6 without metastases . since there was no regularity in the distribution of obtained values of nlr and plr we made the mann - whitney u test . \n mean values are presented with a median and interquartile percentiles . \n there was no significant difference in nlr between patients without and with metastases ( p = 0.614 ; p = ns ) as well as in plr ( p=0,068 ; p = ns).conclusion : there must be a link between the immune status of the organism and lung cancer development . \n immune cells have become of interest in recent years and much work has been done to study their role in the genesis of cancer but it did not give satisfactory results . \n further clinical studies on large number of patients and further laboratory examination of the role of immune cells in cancer development and suppression are required .", "id": 883} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfocal segmental glomerulosclerosis ( fsgs ) is a pathological term to indicate glomerular lesion associated with various etiological factors . in native kidneys ,\n, fsgs can be classified as recurrent disease or fsgs associated with chronic transplant glomerulopathy , calcineurin inhibitor ( cni ) toxicity and in long - standing grafts with hyperfiltration injury .\nthe incidence of recurrent fsgs is approximately 30% and secondary disease occurs in 10 - 20% of the cases .\nthe distinction between these various types is difficult because of lack of pretransplant diagnosis and overlapping morphological features .\nwe analyzed 24 graft biopsies with fsgs and tried to etiologically classify them basing on the accompanying morphological features on the graft biopsies and clinical features .\nit is important to diagnose the condition adequately and promptly to protect the graft and inhibit the progression of the disease .\nout of 363 allograft biopsies received between january 2012 and december 2013 , 24 diagnosed as fsgs were included in the study .\nthree routine stains were done in all biopsies , which included hematoxylin and eosin , periodic acid - schiff 's , and masson 's trichrome .\nimmunofluorescence with immunoglobulin ( ig ) g , igm , iga , c3c and c1q was done .\ncriteria to diagnose fsgs included segmental sclerosis , hyalinosis and or lipid deposition , focal or segmental collapse of the tuft with prominence of podocytes of variable degree depending on the histological type of lesion diagnosed .\nmean serum creatinine level was 2.7 mg / dl and mean 24 h urinary protein was 3.2 g. secondary fsgs was reported in 18 cases ( 75% ) .\ncauses included chronic humoral rejection in seven cases ( 38% ) , cni ( cyclosporine and tacrolimus ) toxicity in six cases ( 33% ) , and in long - standing grafts with hypertensive nephron loss and hyperfiltration injury in five cases ( 29% ) .\nthe type of donor , biochemical parameters and pretransplant diagnosis for various categories are given in table 1 .\nrecurrent and new - onset primary diseases seven cases with chronic glomerular and tubulointerstitial changes with positive c4d were classified as chronic humoral rejection .\nglomerular changes included thickening and duplication of basement membrane , increase in mesangial matrix and cellularity , and focal segmental sclerosis [ figure 1 ] .\nc4d was given as positive when 10 - 50% of capillaries ( c4d2 ) or more than 50% of capillaries ( c4d3 ) showed linear circumferential staining .\npositive c4d and segmental lesion in chronic humoral rejection ( 200 ) chronic humoral rejection mean serum creatinine level was 2.7 mg / dl and 24 h urinary protein was 2.8 g. six lesions were classified as cni toxicity .\nhistological features included striped fibrosis in interstitium and nodular hyaline arteriolar sclerosis ( ah2 and ah3 ) in vessels [ figure 2 ] .\nnodular hyaline arteriolar sclerosis ( periodic acid - schiff , 200 ) calcineurin inhibitor toxicity mean serum creatinine level was 2.1 mg / dl and mean 24 h urinary protein was 800 mg .\nhyperfiltration injury was diagnosed in five cases where hypertensive glomerular changes such as thickening and wrinkling of basement membrane , ischemic collapse of the tuft , and widening of bowman 's space and fsgs was seen .\nvessels showed marked subintimal fibrosis with > 50% narrowing of lumen and associated with chronic tubulointerstitial changes .\nmean serum creatinine level was 2.1 mg / dl and mean 24 h urinary protein was 300 mg . clinical and morphological details are given in table 4 .\nfocal segmental glomerulosclerosis is a pathological term to indicate glomerular lesion associated with various clinical situations in renal allografts .\nfsgs is a common cause of end - stage disease and recurrence in grafts is approximately 30% .\nwe classified fsgs in renal grafts as recurrent disease , new - onset primary fsgs in cases where the native diagnosis was not fsgs , and secondary fsgs when associated with drug toxicity , chronic rejection or hypertension , depending on the clinical features and in correlation with various morphological features that are associated with fsgs .\nthis number does not indicate the exact incidence , as native biopsy diagnosis is not available in many cases .\nrisk of recurrence includes young age of the patient , presence of mesangial proliferation , and rapid progression to end - stage disease and pretransplant bilateral nephrectomy .\nrecurrence occurs in renal grafts in early post - transplant period . these patients present with heavy proteinuria usually of nephrotic range .\nthis criterion and an available diagnosis of native disease are helpful in diagnosing recurrent disease . in our series , all the four cases had a biopsy diagnosis of fsgs .\nthe type of fsgs in native kidney was available in three cases , and recurrence disease had a similar pattern to native disease .\nrecurrence can be classified as recurrence of same variant ( 51% ) , recurrence of same variant preceded by minimal change disease ( 19% ) and recurrence with a different variant of fsgs ( 19% ) .\ngraft survival is poor and progression to end - stage renal disease is rapid and is as high as 50% . it is therefore important to diagnose and differentiate this entity from other causes of fsgs . ( a ) collapsing glomerulopathy ( jones , 200 ) .\n( b ) focal segmental glomerulosclerosis - not otherwise specified ( h and e , 200 ) chronic transplant glomerulopathy and chronic humoral rejection are other conditions in which fsgs can occur .\nthe mechanism for this is chronic immunological glomerular endothelial and podocyte injury , which is resulting in fsgs .\nthis particular lesion is relatively easy to diagnose as associated features of chronic graft damage are seen , and c4d is positive .\nthese patients presented in late post - transplant period mostly after 3 years and presentation is due to the rise in creatinine and mild proteinuria .\nthese lesions are purely based on pathology diagnosis as serum levels do not correlate with the extent of renal damage and clinical features are not specific .\nglomerular changes include glomerular hypertrophy , capillary collapse , focal segmental or focal global sclerosis .\nfsgs results from hyperfiltration injury due to loss of functioning nephrons rather than direct toxic effects on podocytes .\npresence of hyaline arteriopathy , stripped fibrosis , [ figure 4 ] tubular atrophy with or without isometric vacuolation , and absence of heavy proteinuria help to diagnose this particular entity .\nstriped fibrosis ( masson 's trichrome , 100 ) the true incidence of glomerulonephritis in grafts is not exactly known and ranges from 4% to 20% .\nmembranous nephropathy and fsgs are most common of the glomerulonephropathies that can be seen in grafts with an incidence of 1 - 9% .\nwe diagnosed two cases of new - onset fsgs in patients presenting with nephrotic range proteinuria .\nhistologically , there were no features of hypertension or cni toxicity and c4d was negative .\nnew - onset fsgs has favorable clinical course when compared with recurrent disease and hence it is important to identify this lesion . in long - standing grafts with nephron loss and chronic tubulointerstitial changes\nwe described this entity separately when arterial changes are predominant and tell - tale signs of cni toxicity are absent .\nan attempt was made to etiologically classify these lesions as there is a difference in treatment and prognosis .\nit is important to make a diagnosis carefully using clinical information and pathology when a decision about second transplant has to be made .", "answer": "recurrence of fsgs in renal allo grafts is a major cause of graft loss . in this context \n , we tried to diagnose and classify fsgs in renal allografts . \n indications for biopsy included graft dysfunction and/or proteinuria . \n three hundred and sixty - three graft biopsies were studied over a period of 2 years . \n we classified fsgs into recurrent fsgs , new - onset primary fsgs and fsgs secondary to chronic humoral rejection , calcineurin inhibitor toxicity , and nephron loss and hyperfiltration injury . \n twenty - four cases were diagnosed as fsgs , constituting 6.6% . \n secondary fsgs was the most common fsgs in grafts in our study . \n incidence of recurrent fsgs may not be accurate as pretransplant biopsy is available in very few cases .", "id": 884} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome\n\nPaper sections:\n\nArsenic exposure is a global public health issue, with more than 100 million people being exposed primarily from drinking water.1 Arsenic exposure has been linked to a series of human diseases, including cancers, diabetes, and cardiovascular disorders.2\u20134 Different molecular mechanisms and modes of action are associated with arsenic toxicity. For example, arsenic activates inflammatory signaling and alters DNA methylation and gene expression.5\u20137 Recently, the role of the gut microbiome in arsenic metabolism and toxicity has been demonstrated in different model systems.8\u201310 The gut microbiome is a very complex dynamic system which contains trillions of bacteria and 100-fold more unique genes than the human genome.11 The gut microbiome is deeply involved in host metabolism and can be readily perturbed by external factors, raising the possibility that arsenic exposure could alter the gut microbiome and its functions.12,13 Our previous research clearly demonstrated that the gut microbiome interplays with arsenic exposure: arsenic can perturb the gut microbiome community structures and its metabolic profile;13 the gut microbiome phenotypes/variations alter the biotransformation of inorganic arsenic.9,14 Likewise, a recent study by Dheer et al. demonstrated that arsenic at environmentally relevant doses altered the gut microbiome and microbiome/host functions.15
The establishment of the gut microflora is a temporal and sensitive process occurring after birth.16 The colonization of gut microbiome during early life is highly sex-dependent.17,18 Meanwhile, sex-specific effects of arsenic metabolism and toxicity have been reported, although with little of the molecular mechanism being identified.19 For example, previous studies have revealed that arsenic methylation is more efficient in females than in males.19 Likewise, males are more susceptible than females to develop skin lesions when exposed to arsenic.20 Taken together, sex is an important factor to be considered when exploring the complex interaction among host, gut microbiome, and arsenic toxicity. However, it remains unclear whether sex influences the gut microbiome response to arsenic exposure. In this study, we employed 16S rRNA gene sequencing and metagenomics to address this intriguing question. Our results reveal that arsenic exposure altered the trajectories (i.e., time-dependent changes of gut microbiome compositions) and functional metagenome of the gut microbiome in a sex-specific manner.
The experimental design and workflow are described in the Supporting Information and Figure S1. Briefly, we divided 20 female mice and 20 male mice into four groups: Group A, 10 female mice as controls; Group B, 10 female mice treated with 10 ppm arsenic as previously described;13 Group C, 10 male mice as controls; and Group D, 10 male mice treated with 10 ppm arsenic. Then, we collected the fecal pellets from individual animals at two different time-points (day 0 baseline and 4 weeks after arsenic treatment) and applied 16S rRNA sequencing technology to determine the fecal microbiome compositions (Figure 1). Finally, the changes of functional metagenome and pathways induced by arsenic exposure were determined by metagenomics sequencing (Figure 2).
16S rRNA sequencing results reveal that there is a remarkable difference of gut microbiome between male and female mice, as shown in Figure 1A and Figure S2. After a 4-week arsenic treatment, the gut microbiome changed in both male and female mice. According to the principal coordinate analysis (PCoA) of beta diversity (Figure 1B), the difference of gut microbiome community structures in arsenic-treated female mice is more significant than that in male mice when compared to corresponding controls. These results reflect that gut microbiome phenotypes driven by host sex have different sensitivity to arsenic exposure. Meanwhile, time plays a role in shaping the gut microbiome profiles regardless of treatment, as shown in Figure 1B and Figure S2B, raising the possibility that arsenic exposure may perturb the normal trajectory of the gut microbiome. To further examine this, we compared the gut microbiome profiles over time for both controls and treated animals. Figure 1C and D summarizes the fold changes of a few representative genera that were statistically different between day 0 and 4 weeks. Evidently, the change patterns of the gut microbiome were different for controls and treated animals, indicating that arsenic exposure affected the trajectory of the gut microbiome. Moreover, a strong sex-specific response was observed. For example, Dorea decreased in female mice after a 4-week exposure, while it significantly increased in treated males. Likewise, Akkermansia had an ~7000-fold increase in the female arsenic-treated group; however, this genus did not show any significant change in males after arsenic exposure (Figure 1C and D). More detailed information on gut bacteria alterations from arsenic treatment is listed in Tables S1 and S2. Taken together, arsenic exposure altered the trajectory of the gut microbiome in a sex-selective manner.
We next used metagenomics to examine whether arsenic exposure also perturbed the functional metagenome in a sex-specific way, as the functional impact is more relevant to the gut microbiome and host. Figure 2 shows that a number of metabolic pathways were significantly altered by arsenic exposure. Similar to the changes of the microbiome profiles, the functional pathways were also differentially perturbed by arsenic in male and female mice. For example, arsenic treatment up-regulated many functional pathways in females, with several of them being related to metal resistance (such as mercury resistance operon, zinc resistance, and the mdtABCD multidrug resistance cluster) and the cell transport system (such as glutathione-regulated potassium-efflux system, ATP-dependent efflux pump transporter Ybh, general secretion pathway, and iron acquisition in Streptococcus). In arsenic-treated males, the pathways of nitrogen, carbon, and sulfate metabolism were significantly affected. For example, the hexose phosphate uptake system and phospholipid and fatty acid biosynthesis were remarkably down-regulated in arsenic-treated males, whereas functional pathways like ammonia conversion, denitrification, and cluster Ytf and the putative sugar transporter were significantly increased in treated males. Interestingly, the previous study by Dheer et al. found elevated tissue nitrite in hosts, highlighting the potential role of host\u2013microbiome interaction in mediating nitrogen metabolism.15 In summary, arsenic has different effects on the functional metagenome in male and female mice.
The interaction among host, gut microbiome, and xenobiotics is a very complex dynamic process. Previously, we have demonstrated that gut microbiome phenotypes driven by host genetics and bacterial infection largely influence the biotransformation of arsenic in the host.9,14 Here, we show that that host sex also serves as an important factor to influence the gut microbiome compositions and could further affect the gut microbiome response to arsenic exposure. It was previously documented that the female is more resistant to arsenic exposure than males.19\u201321 It is interesting to notice that gut bacteria in arsenic-treated female mice but not male animals have significantly increased heavy metal resistance and cell-efflux capability, which may partially contribute to the different sex susceptibilities to arsenic exposure. Future studies are needed to further elucidate this intriguing question.
In summary, our results show that arsenic exposure significantly altered the trajectory of the gut microbiome over a 4-week dosing period, with multiple components of gut bacteria being significantly changed in a sex-selective fashion. Consistent to this, metagenomics data also revealed that the functional metagenome was differentially perturbed in male and female mice. Taken together, this study provides strong evidence for the first time that host sex plays a role in the gut microbiome responses to environmental toxicants, such as arsenic. Several limitations are associated with this study, including the high arsenic dose, short exposure time, and the use of fecal microbiome to infer changes of gut microbiome. In particular, the impact of arsenic on the host functions was not assessed in this study, which may largely drive the microbiome changes. Further study is warranted to shed light on these aspects.
", "answer": "The gut microbiome is deeply involved in numerous aspects of human health; however, it can be readily perturbed by environmental toxicants, such as arsenic. Meanwhile, the interaction among host, gut microbiome, and xenobiotics is a very complex dynamic process. Previously, we have demonstrated that gut microbiome phenotypes driven by host genetics and bacterial infection affect the responses to arsenic exposure. The role of host sex in shaping the gut microbiome raises the question whether sex plays a role in exposure-induced microbiome responses. To examine this, we used 16S rRNA sequencing and metagenomics sequencing to analyze the changes of the gut microbiome and its associated functional metagenome in both female and male C57/BL6 mice. Our results clearly demonstrated that arsenic exposure perturbed the trajectory and function of the gut microbiome in a sex-specific manner.", "id": 885} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nzika and chikungunya viruses are both transmitted by aedes aegypti mosquitoes and are associated with an abrupt onset of fever , arthralgia , myalgia and rash . in brazil , acute exanthematous outbreaks related to zika ( zikv ) and chikungunya viruses ( chikv ) have been reported in many regions and sometimes as co - infections , , , .\nacute chikungunya infection generally leads to prominent joint symptoms with moderate to severe arthralgia and arthritis that may persist for months and even years .\nrarely , encephalitis and other neurological involvements may also complicate chkv infection such as recently reported a neonatal encephalitis in brazil with similar lesions on brain scan as those previously described in the la runion islands , , .\nin all these situations , a rapid diagnosis is of importance for epidemiological purposes and clinical management . in zikv infections ,\nthe molecular diagnosis in serum is generally possible until the first six days of symptoms onset and , later on , urine or saliva is used , .\nzika detection in urine may help in ascertaining the diagnosis after the initial period of viremia in areas with co - circulation of zikv and dengue virus ( denv ) , where serologic cross - reactions may occur , but evidence for that associated with chikv infection has not been shown .\nan expanded window for diagnosis in chikv is also needed since igm seropositivity may persist for months after the initial acute infection .\nmany other viruses have been detected in semen , such as ebola , hiv , hbv , hpv , hsv-1 , hsv-2 , marburg , but there has been no published data so far on the presence of chikv in semen , , , , .\nwe report the presence of chikv rna for a prolonged period of time in the urine and semen of an adult with a dual infection with dengue virus type 3 for a prolonged period of time .\na 25-year - old man from salvador , brazil presented with a 6 days of high fever , arthralgia , myalgia , headache and photophobia .\nhe also reported a burning sensation on his eyes and a non - pruritic rash in the trunk and upper limbs on the first 3 days , and complained of pain involving the ankles , knees , shoulders , wrists , lower back , and neck .\nof note , he also reported a transient burning sensation in the urethra and genital region that started 3 days before the onset of symptoms and resolved spontaneously . on examination\nthe patient was febrile with a temperature of 38.3c , had a maculopapular erythematous diffuse rash , joint enlargement with mild inflammatory signs affecting the wrists , the metacarpophalangeal and metatarsophalangeal joints as well as the ankles .\nthe patient was not able to raise his arms on command because of shoulder pain and was eating with difficulty because of pain involving his temporomandibular joint .\nblood samples were drawn for viral workup , semen was also requested due to the complaint of dysuria , and the possibility for zika diagnosis since the patient could not provide a urine sample at that time .\nblood , urine and semen were collected again after 30 days of symptoms onset and were further processed .\nserum and semen samples were submitted to viral rna extraction using a maxwell total viral nucleic acid 16 purication kit ( promega , usa ) regarding that the semen sample , the incubation time of the lysis step was extended to 30 min .\nurine sample was submitted to viral rna extraction using qiamp viral rna purification ( qiagen , usa ) .\nsubsequent to viral rna extraction , all samples were submitted to rt pcr technique ( accessquick system , promega , usa ) to screen for chikv , zikv and denv using conventional techniques , , .\nserum and semen specimens were positive for chikv rna in the first collected samples ; semen and urine specimens were positive for chikv rna after 30 days of symptoms onset , with negative results in serum .\ndenv-3 rna was positive in serum specimen when first collected 6 days after the initiation of symptoms and was not tested thereafter .\ntable 1 presents the clinical findings and molecular results during the time frame of infection .\nthe patient made use of prednisone starting on the 2nd day of symptoms onset with 40 mg qd for 10 days , tapering to 20 mg qd for the next 10 days , and 10 mg qd for the last 8 days , with an uneventful course and no clinical findings after 30 days .\nebola rna ( ebo - rna ) can be detected in up to 290 days after clinical manifestations and ebola infectious particles in up to 70 days .\ntransmission of ebola virus ( ebov ) from a male survivor to a female has been documented 179 days after illness in liberia . in another study ,\npersistence of ebo - rna could be found in semen specimens at least 9 months after the onset of symptoms with important consequences related to sexual transmission .\nmany papers have reinforced the sexual transmission of zikv since foy et al . have suggested its relationship , , , .\nthis report , besides describing a patient with classical signs of zikv , drew attention to symptoms of prostatitis with hematospermia .\nour patient reported a burning sensation in the urethra and the genital region and may also have had a transient prostatic involvement with detection of chikv rna in semen .\nzika rna has been detected in semen for up to 6 months after the onset of symptoms and is involved in male - to - female as well as in female - to - male transmission , .\nstudying human papilloma virus ( hpv ) have found a high prevalence of this virus in semen \n27.2% of healthy adults in amsterdam and using fluorescence in situ hybridization ( fish ) for hpv - dna and immunocytochemistry for the hpv - l1 and hpv - e4 proteins , the authors detected hpv - dna , hpv - e4 and hpv - l1 in exfoliated keratinocytes present in some hpv16-positive semen samples , indicating the presence of hpv viral particles .\neven though alphavirus envelope glycoproteins function as the attachment point to cells , no human cell surface receptor has been implicated in cell entry so far .\nprimary peripheral blood cells such as cd4 + t lymphocytes , primary cd14 + monocytes and dendritic cells were reported to be refractory to chikv binding and infection .\nmacrophages , on the other hand , are highly sensitive to chikv and showed cytopathic effect following chikv infection , .\nmononuclear cell infiltration and viral replication in the muscles ( particularly skeletal muscle progenitor cells , not muscle fibers ) and joints are associated with myalgia and arthralgia and synovial macrophages have been shown to contain viral rna months after infection .\nit may be postulated that an inflammatory infiltration with macrophages in the genital tract may be the source of the chikv , leading to mild symptoms and an unknown persistence time in semen .\nthe detection of chikv in semen has many important implications , including the possibility of sexual transmission .\neven though we did not perform cytopathic assays for chikv , this finding must be further investigated .\nwe did not find any other study showing evidence of chikv in semen and , specially , for such a long period since the onset of symptoms .\nanother unique finding in our study was the detection of chikv in urine after 30 days of the initial symptoms contrasting with recent findings in literature showing no detection of chikv in urine after the first week of symptoms onset .\nthis could provide an expanded window for the diagnosis of a recent infection with chikv .\nthe use of prednisolone may have contributed to the prolonged viral shedding and another factor that may , in part , have added to that was the possible interaction between chikungunya and dengue type 3 . with the ongoing circulation of denv , chikv and zikv in brazil , such a finding of dual infections will be increasingly seen and reported , as we recently published for chikv and zikv . in india ,\nan estimate of co - infection with chikv and denv using serological markers estimated point prevalences on the range of 5.79.5% . in 1964\nmyers and carey reported that seven patients out of 332 patients ( 2.1% ) from south india had a simultaneous increase in antibody to both chikv and denv virus and that these patients had also an unremarkable clinical course and an expected development of antibodies to both agents , indicating that the host response was not altered by the dual infection . during an outbreak of both chikv and denv-1 in toamasina , madagascar , in 2006 ,\n10 out of 55 patients sampled ( 18.2% ) were shown to be co - infected with both virus with no complications recorded .\nhowever , chahar et al . reported that during the 2006 dengue outbreak in delhi six patients were co - infected with chikv and denv ( with denv-3 in 5 out of 6 ) , 2 of these patients had dengue hemorrhagic fever with central nervous system ( cns ) involvement and one patient died .\nmore recently , villamil - gomez et al . reported a 49-year - old male from colombia with a febrile illness , bilateral conjunctivitis and a pruritic rash that was diagnosed with zikv , chikv and denv and had an uneventful course .\nthe true extent of chikv - denv co - infection has been hampered by current diagnosis largely based on clinical grounds with unavailability of molecular methods in many parts of the world , .\nthis work was supported by the ministry of education coordenao de aperfeioamento de pessoal de nvel superior ( capes ) zika fastrack number 88887116628/2016 .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\na copy of the written consent is available for review by the editor - in - chief of this journal on request .", "answer": "absractwe report the presence of chikungunya ( chikv ) rna in the blood , urine and semen during the acute phase of the disease in an adult with a dual infection with dengue virus type 3 . \n the patient , a 25 yr - old man from salvador , brazil , reported a 6-day duration of high fever , arthralgia , myalgia , headache and photophobia.blood and semen specimens were positive for chikv in the first collected samples ; semen and urine specimens were positive for chikv after 30 days of symptoms onset . \n denv-3 rna was positive in blood specimen when first collected 6 days after the initiation of symptoms.we describe for the first time the presence of chikv rna in urine and semen for an extended period of time and we address the possible implications of these findings for diagnosis and transmission dynamics .", "id": 886} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit could be an incidental diagnosis in adulthood or could present with obstructive symptoms from the herniated viscera .\nsurgical treatment consists of direct closure or mesh placement for the diaphragmatic defect , or suturing by transabdominal or transthoracic access .\nwe report a patient with morgagni hernia who underwent a laparoscopic mesh placement with reduced port surgery ( rps ) .\nan 85-year - old female presented in er with a 2-day history of upper abdominal discomfort and loss of appetite .\nshe had never experienced the same symptoms previously , and she denied any history of abdominal trauma .\nphysical examination revealed no palpable mass in the upper abdomen , and local tenderness on upper abdomen was shown without any peritoneal inflammatory signs .\nserum blood test showed a hyperlipidemia and mild elevation of urea nitrogen ( total cholesterol , 250 mg / dl ; urea nitrogen , 22.5 mg / dl ) .\na ct scan showed a huge diaphragmatic anterior hernia with a segment of transverse colon and fat tissue migration ( fig .\nthe diagnosis of morgagni hernia was made and the patient was considered for repair of the diaphragmatic defect by the laparoscopic approach . under general anesthesia in the lithotomy position , the sils port ( covidien , tokyo , japan ) was inserted into a 2.5-cm umbilical incision vertically .\nafter inspection of the visceral space , a second port , 12 mm in size , was inserted into the left lower abdomen .\nthe herniated bowel and fat tissues were gently pulled down with grasping forceps and placed entirely into the abdominal cavity ( fig .\nthe defect was ovoid and approximately 5 cm in size , and difficult to close by the suturing technique ; therefore we performed mesh placement with gore - tex dual mesh ( gore inc .\noperation time and operative blood loss were 157 min and 5 ml , respectively .\nthe patient started to eat a soft meal on day 1 after surgery and was discharged from our hospital on day 8 after surgery without any symptoms .\nafter 6-month , 12-month , and 24-month follow - ups , the patient had no sign of recurrence of the morgagni hernia ( figs . 4 and 5 ) .\ngiovanni - battista morgagni first described this type of hernia in 1769 . at present ,\nit could be an incidental diagnosis in adulthood or could present with obstructive symptoms of the herniated viscera .\nsurgical treatment is required to relive current symptoms or to prevent possible future complications such as strangulation ileus or incarceration .\noriginally , direct closure of the hernia site or mesh placement was used as the surgical options by laparotomy or thoracotomy .\nrecently , the laparoscopic procedure has become available to treat this type of hernia and has bought a number of advantages such as reduced pain , shorter recovery time , and cosmetic benefits .\nin addition , recent trends in laparoscopic procedures have been toward minimizing the number of incisions to achieve less invasiveness .\nexamples of such approaches are single incision laparoscopic surgery ( sils ) and reduced port surgery ( rps ) .\nonly one report previously described morgagni hernia repair using single port access and closing the hernia site by non - absorbable suturing into extra - abdominal region .\nthis report was very successful , however postoperative pain might be occurred because of suturing tension by lifting the interrupted sutures to close the hernia site .\nsome technical problems associated with sils have been reported : restriction of the working field and interference of surgical instrument .\nthe sils technique does not rely on triangulation , which is one of the core principles of conventional laparoscopic surgery , allowing adequate operative exposure while maintaining an ergonomic position for the surgeon and assistant .\nconsequently , the inherent technical challenge that arises from the sils technique is that of a compromised view and locomotive field . therefore unfavorite outcomes such as longer operative time and possibly higher complication rate have been reported in early period of sils operation .\na small additional port or a reduced number of ports as with rps are modifications that may overcome these problems . in combination with the sils port and the additional port\nenable the performance of dual - port surgery , even for complex operation such as laparoscopic gastrectomy .\nthis type of repair is technically easy and should have a high probability of success because of the tension free condition .\nalso , less postoperative pain is also expected , compared to the external knot tying technique .\nthoracoscopic approach is also other option for this type of hernia as a less invasive treatment , although the benefits over conventional laparoscopic approach have not been cleared .\nalthough the benefits of sils or rps over conventional laparoscopic surgery have not been established , either sils or rps could be the first choice for symptomatic morgagni hernia repair because of the acceptable operation time , blood loss , and clinical outcome .\nbasically , cosmetic benefits and less operative pain are also expected as advantages of sils or rps originating from fewer incisions . in addition , tissue trauma and port - related complications such as organ damage , adhesions , bleeding , wound infections and hernias could be decreased . for the future direction , additional\nthis approach is safe and can be the good indication for this kind of hernia .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .", "answer": "highlightsmorgagni hernia is a rare diaphragmatic hernia and standard therapy has not been established.the laparoscopic repair of a rare diaphragmatic morgagni hernia in an elder patient using the reduced port approach is described.this reduced port approach is a good indication for this type of hernia because of less invasive ness , cosmetics and safety .", "id": 887} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npapillary thyroid carcinoma ( ptc ) is the most frequent type of thyroid malignancy , and the usual metastasis sites include the locoregional lymph nodes .\ndistant metastasis of ptc is rare and usually involves the lungs , liver , bones and brain .\nthe skin metastasis of ptc is a very rare condition , and the scalp is the most frequent cutaneous area which is involved .\nother cutaneous areas that are involved with less frequency are the cheeks , shoulders , arms , abdomen and thighs .\na 64 year - old female with past medical history of metastatic papillary thyroid carcinoma ( ptc ) with both liver and lung metastasis presented with a 2.5 3 cm erythematous tender nodule in right parietal scalp of two months duration .\nshe had a past medical history of total thyroidectomy and also had received repeated doses of radioactive iodine ( rai ) therapy in the past two years .\nher last dose of rai131 ( 200 mci ) was three weeks prior to the time of presentation .\nshe also had a history of subglottic mass as a result of thyroidal carcinoma involvement with severe tracheal stenosis , and had undergone tumoral resection and tracheal anastomosis and partial hemilaryngectomy two years ago because of subglottic involvement by thyroidal carcinoma .\nhigh resolution computed tomography ( hrct ) demonstrated multiple metastatic nodules in both lungs and loculated left side pleural effusion consistent with advanced metastatic involvement .\na differential diagnosis of pillar cyst and metastasis was given by dermatologist for scalp lesion .\nhistopathologic examination of the lesion revealed skin tissue with tumoral involvement of the dermis composed of numerous follicles ( likely thyroid follicles ) , lined by relatively large cuboidal epithelial cells with round nuclei , fine chromatin pattern , little granular cytoplasm and eosinophilic colloidal material within some of follicles , and mitosis , which was consistent with metastatic thyroidal carcinoma [ figures 1 and 2 ] .\nshe was discharged with suppressive therapy with levothyroxine and referred to oncology clinic for continuation of the treatment plan .\nscalp lesion biopsy showing skin tissue with tumoral infiltration of dermis by numerous follicles ( likely thyroid follicle ) , consistent with metastatic thyroidal carcinoma ( h and e , 40 ) scalp metastasis of thyroidal carcinoma composed of numerous follicles lined by relatively large cuboidal epithelial cells with round nuclei , fine chromatin , little granular cytoplasm and eosinophilic colloid material within some of follicles with mitotic division ( h and e , 400 )\nthe skin metastasis of ptc is mostly associated with aggressive and disseminated disease and shows a poor outcome .\nsome authors suggested that the average patient survival time after discovering of skin metastasis is 19 months .\nhere , we have reported a case of scalp metastasis of ptc in a patient with metastatic pulmonary and liver involvement .\nmetastasis of thyroid cancer should be considered in the differential diagnosis of scalp tumors in any patient with a history of thyroidal carcinoma ; and , excisional skin biopsy is necessary for confirming the diagnosis .", "answer": "the skin metastasis of papillary thyroid carcinoma ( ptc ) is a rare condition and the lesions should be differentiated from primary skin tumors . \n the scalp is the most frequent site which is involved in skin metastasis of ptc . \n it shows the poor outcome and aggressive nature of disease . in this report \n , we aim to present a case report of a 64 year - old female with scalp metastasis of ptc in the context of disseminated pulmonary and liver metastasis .", "id": 888} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe number of older adults affected by dementia has been rising significantly in japan and \n a number of other countries1 , 2 .\nmild cognitive impairment ( mci)3,4,5,6 is considered to be a \n preclinical stage of dementia .\nstudies have revealed that approximately 10% to 15% of people \n with mci progressed to dementia annually7,8,9 . in \n order to reduce the number of people who experience cognitive dysfunction , it is important \n to delay , or even reverse , the progression of mci to dementia .\nwhile aging is regarded as the greatest risk factor for \n cognitive dysfunction10 , several studies \n have indicated that habitual exercise and physical activity may have a beneficial effect on \n the prevention of dementia11,12,13,14,15 .\na wide variety of exercises , such as walking , have been recommended for older adults in \n efforts to maintain and promote health .\naquatic exercises in particular are recommended for \n older adults with obesity and osteoarthritis16,17,18 . \n\none such aquatic exercise regimen is synchronized swimming , which is suitable for older \n adults , as the swimmer may stand on the floor of a shallow pool19 .\nwhile a number of studies have indicated that land - based exercise exerts a beneficial \n effect on cognitive function in older adults11,12,13,14 , no studies to date have examined the \n effect of synchronized swimming on cognitive function in older adults .\nthe study participants were recruited from among 23 women practicing synchronized \n swimming - exercise at a sport club in fukushima - ku , osaka city , japan ( ss group ) .\nall \n participants provided written informed consent , after having gained a full understanding of \n the present study .\nthe study was approved by the ethics committee of the osaka university of \n health and sport sciences ( approval number 15 - 21 ) . synchronized swimming\nwas performed in a shallow pool from 1.2 to 1.3 meters in depth and \n the participants were allowed to touch the bottom of the pool with their hands and feet \n during the performance .\nparticipants who had participated in the olympic games or the \n domestic competitions for seniors were excluded .\nparticipants practiced synchronized \n swimming twice a week for 90 minutes under the supervision of an instructor , who had been a \n member of the japanese synchronized swimming team .\nthe ages of participants in the ss group \n ranged from 49 to 85 years ( mean age : 69.8 11.6 years ) , and the duration of synchronized \n swimming experience ranged from 1 to 39 years ( mean year : 23.9 12.6 years ) .\ncontrol participants were recruited age - matching women with exercise custom other than \n synchronized swimming .\nthey were 36 individuals participating in a health promotion program \n at our university in 2015 , and provided written informed consent as controls ( age range : \n 4977 years ; mean age : 67.0 6.0 years ) . among the participants in the control group , 16 \n participants exercised three or four times a week ,\n17 exercised once or twice a week , and 3 \n exercised one to three times a month .\ncognitive functions was compared between the two groups using the japanese version of the \n montreal cognitive assessment ( moca - j)20 . \n\nthe moca is a brief cognitive test containing test items related to memory , language , \n executive function , working memory ( attention ) , visuospatial recognition , abstract thinking , \n and orientation21 .\nthe sensitivity and \n specificity of the moca - j in screening for mci has been demonstrated20 .\nthe assessment takes only approximately 10 minutes to \n complete , and a number of studies have demonstrated the effectiveness of moca - j as a \n screening tool for mci21,22,23 .\ntotal scores of less than 26 points may be indicative of mild cognitive \n impairment .\ninformation on the presence of neurological disease , psychiatric disease , alcoholism , and \n hospitalization was collected via an interview .\nunpaired t - tests were used to compare results \n between the ss group and control group when data were normally distributed , while u tests \n were performed when the data were not normally distributed .\ntwo - sided p values of < 0.05 \n were considered to indicate a statistically significant difference .\nno significant differences in education level were observed between the control and ss \n groups ( 12.1 2.0 and 12.2 1.8 years , respectively ) . in addition , no significant \n differences in total moca - j scores were observed between the two groups ( 22.2 3.6 and 23.2 \n 3.1 , respectively ) .\ntwenty - nine participants in the control group and 17 in the ss group \n scored below 26 on the moca - j and were suspected of having mci ( table 1table 1.comparison of moca - j between the control group and the ss groupscorecontrol group ( n=36)ss group ( n=23)moca - j<2629 ( 80.6)17 ( 73.9)267 ( 19.4)6 ( 26.1)no significant differences are shown between the two groups .\nmoca - j : japanese version of montreal cognitive assessment ; ss : synchronized \n swimming ) . with regard to moca - j sub - scores , significant differences in delayed recall \n ( p=0.005 )\nhowever , no significant differences were \n observed with regard to measures of but not in visuospatial / executive function , naming , \n attention , language , abstraction , or orientation ( table \n 2table 2.comparison of moca - j sub - score between the control group and the ss groupcontrol group ( n=36)ss group ( n=23)visuospatial / executive function ( 5)3.5 1.03.4 1.0/5naming ( 3)2.9 0.43.0 0.0attention ( 6)4.9 1.14.8 1.0language ( 2)1.6 0.91.7 0.8abstraction ( 2)1.1 0.80.9 0.7delayed recall * ( 5)1.8 1.73.0 1.4orientation ( 6)5.8 0.45.6 0.7total scores22.2 3.623.2 3.1values are shown as the mean sd . *\nmoca - j : japanese version of montreal cognitive assessment ; ss : synchronized \n swimming values are shown as the mean sd . * p<0.005 for the difference between the two groups .\nno significant differences in years of education or total moca - j scores were observed \n between the ss group and the control group in the present study .\nthe results of total moca - j \n scores in the present study align with those of a previous report involving 1,552 \n participants ( mean age : 72 years ; mini - mental state examination score > 24 points ) living \n in sasaguri , fukuoka prefecture , in which mean the moca - j score was 22.4 3.024 .\nhowever , in the comparison of moca - j \n sub - score in the present study , delayed recall scores , which are considered indicative of \n recent memory function , were significantly higher in the ss group than in the control \n group .\nsuzuki et al.25 conducted an \n exercise - based intervention program that included exercise , calculation , word - chain game , \n and multiple tasks using a ladder diagram program ( 90 minutes two times per week for 6 \n months ) with participants aged 65 years or older experiencing mci .\nsignificant differences \n in mini - mental state examination , wechsler memory scale - logical memory i , word fluency \n test - category , and word fluency test - letter scores were observed following this \n intervention . in synchronized swimming , participants must swim and act in a coordinated \n manner with other swimmers while performing to music .\nin other words , the swimmers are \n required to perform multiple coordinated tasks in an aquatic setting to be more complex than \n those of the multicomponent exercise program developed by suzuki et al25 .\nmoreover , it has been reported that group music intervention \n delayed the deterioration of cognitive function , particularly short - term recall among aging \n adults with mild and moderate dementia26 . \n\nperforming to music in synchronized swimming might be one of the reason that delayed recall \n scores were significantly higher in the ss group than in the control group .\nvoelcker - rehage et al.22 reported that \n not only physical fitness , as indexed by cardiovascular fitness and muscular strength , but \n also aspects of motor fitness , such as movement speed , balance , motor coordination , and \n flexibility exhibit associations with executive control and perceptual speed .\nthey further \n demonstrated physical and motor fitness to be differentially related to various cognitive \n processes using functional brain magnetic resonance imaging . given that most synchronized \n swimmers exhibit good cardiopulmonary function , muscle strength , and flexibility27 , it is also possible that enhanced \n physical fitness may exert direct positive effect on cognitive function . according to a report by suzuki et al.28 , 12 months of multicomponent exercise\nin particular , positive effects were \n observed for general cognitive function , immediate memory , and language ability .\nwe \n therefore consider that synchronized swimming exerted beneficial effects on cognitive \n function in the participant who experienced synchronized swimming for one year . in conclusion , the results of the present study suggest that synchronized swimming may \n improve cognitive function in older adults , particularly with regard to recent memory . no relevant disclosures .", "answer": "[ purpose ] the purpose of the present study was to examine cognitive function in \n middle - aged and older adults regularly engaging in synchronized swimming - exercise . \n [ subjects and methods ] twenty - three female synchronized swimmers ranging in age from 49 to \n 85 years were recruited for the present study . \n the duration of synchronized swimming \n experience ranged from 1 to 39 years . \n the control group consisted of 36 age- and \n gender - matched community - dwelling middle - aged and older adults ( age range : 49 to \n 77 years ) . \n cognitive function was evaluated using the japanese version of the montreal \n cognitive assessment ( moca - j ) and compared between the synchronized swimmers and control \n participants . \n [ results ] no significant differences in mean total moca - j scores were \n observed between the synchronized swimmers and control participants ( 23.2 3.1 and 22.2 \n 3.6 , respectively ) . \n twenty - nine subjects in the control group and 17 in the synchronized \n swimming group scored below 26 on the moca - j , indicative of mild cognitive impairment . \n \n significant differences in delayed recall but not in visuospatial / executive function , \n naming , attention , language , abstraction , or orientation were also observed between the \n two groups . [ conclusion ] the results of the present study suggest that synchronized \n swimming has beneficial effects on cognitive function , particularly with regard to recent \n memory .", "id": 889} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndescriptive investigation of a cluster of 5 sfts cases following exposure to an index patient who died from the disease was performed . a 77-year - old male farmer who died from sfts\nfive other cases in the cluster included a 32-year - old male intensive care unit ( icu ) physician ( case 1 ) , a 48-year - old male icu consultation physician ( case 2 ) , a 42-year - old younger son of the index patient ( case 3 ) , and a 45-year - old older son of the index patient ( case 4 ) , as well as a 43-year - old male mortuary beautician ( case 5 ) .\nthe investigation included a review of circumstances and medical records , specimen collection , virus isolation , real - time polymerase chain reaction for viral rna detection , and sequencing and serological tests ( capture enzyme - linked immunosorbent assay [ elisa ] for immunoglobin [ ig ] m antibody , antigen sandwich elisa for igg antibody , and microneutralization tests [ mnt ] ) .\nas for risk assessment of transmission factors , all contactors of the index patient during the period from the beginning ( 25 september 2010 ) to the end ( 8 october 2010 ) were classified through 3 types of contacts , including blood , droplet , and possible airborne contacts . the investigation was reviewed and approved by the ethics committee of china center for disease control and prevention ( cdc ) , which uses international guidelines to ensure confidentiality , anonymity , and informed consent .\nthe index patient was from an sfts - endemic region and first had onset of illness on 25 september 2010 ; was admitted to a local hospital on 28 september with a high fever of 39.5c and vomiting ; and the infection was identified through initial laboratory testing of thrombocytopenia , leukocytopenia , and elevated aspartate aminotransferase level .\nthe patient was diagnosed as a suspected sfts case , and transferred to the intensive care unit the next day , where he received ribavirin , dexamethasone , omeprazole , and cryoprecipitation for therapy . on 2 october 2010 ,\nhis condition deteriorated with hypersomnia , shortness of breath , and mouth mucosal bleeding . on 3 october\n, he appeared confused and showed dyspnea , then was intubated and mechanical ventilated . on 4 october ,\nthe patient was in shock and comatose , developed disseminated intravascular coagulation and multiple organ dysfunction syndrome , and died the next day .\nan important observation was that the index patient had unique hemorrhagic symptoms , including bleeding from mouth mucosa , gastrointestinal lumen , and lungs , which was rare in previously identified sfts patients .\nthe patient s fever remained high ( 39c40c ) until death , although lowered somewhat by giving dexamethasone .\nclinical laboratory values ( table 1 ) showed unusually high level of tissue enzymes , blood urea nitrogen , and creatinine , which might indicate impaired liver , heart , and kidney functions .\nconsistent with the largely reduced platelet count , the index patient had a significantly elongated activated partial thromboplastin time , which represented a largely impaired coagulation function .\nimmediately after death , the corpse was transferred to the patient s home in a local village for a funeral ceremony , then transferred to a crematorium 3 days later .\nlaboratory analysis of a cluster of severe fever with thrombocytopenia syndrome patients in china alt , alanine aminotransferase ; ast , aspartate aminotransferase ; ldh , lactate dehydrogenase ; aptt , activated partial thromboplastin time .\n , negative ; + , weak positive ; + + + , strong positive .\nviral rna copies were calculated according to standard reaction curves , which were established using serially diluted in vitro rna transcripts as standard samples .\nvirus load was determined based on an average conversion coefficient between virus copies and virus titer presented as 50% tissue culture infective dose ( tcid50/ml ) .\nserum samples collected in the acute phase were subjected to immunoglobin ( ig ) m detection with igm antibody capture enzyme - linked immunosorbent assay ( elisa ) , with horseradish peroxidase conjugated recombinant severe fever with thrombocytopenia syndrome bunyavirus ( sftsv ) nucleoprotein as the detection agent .\nserum samples collected in the convalescent phase were subjected to igg detection with sandwich elisa by using recombinant sftsv nucleoprotein as the detection agent .\nvalues for igm antibodies , igg antibodies , and mnt are the reciprocals of the serum dilution .\nrisk factors were assessed using logistic regression analysis ; p < .05 was considered to be statistically different .\nepidemiologic investigations began with interviews with 5 secondary sfts patients and 58 other individuals who had exposure to the index patient from onset of the illness until cremation .\nwe found that all 5 secondary cases had possible blood contact through skin or mucosa .\ncase 1 , the local icu doctor , performed the intubation for the index patient , resuscitating the patient before his death .\ncase 2 , the consultant doctor , traveled from a nonendemic area to the local hospital for a medical consult with the patient , and the patient s blood dropped on his hand when he was helping an icu nurse draw blood without wearing gloves .\ncase 3 , the younger son of the index patient , was a long - distance truck driver not living in the same village , and directly touched the blood flowing from the deceased patient s mouth and nose when he cried on the corpse .\ncase 4 , the older son of the index patient , was also a long - distance truck driver , and took care of the dead body and was wiping off the blood from the face of the corpse .\ncase 5 , a local mortuary beautician , did the make - up for the corpse with gloves and mask , but took them off twice during the procedure . the above 5 cases all developed the disease 715 days after exposure , with only 3 of them having contact with blood after death . in comparison with the index patient\n, all 5 secondary cases had minor clinical features ( table 1 ) , without obvious hemorrhagic manifestations , so they did not receive dexamethasone therapy . except for the major risk factor of blood contact , droplet contact ( n = 4 ) , which included 3 medical staff who were involved in the intubation and the index patient s daughter who cared for him before death ,\nin addition , the risk factor of possible airborne transmission ( being in the icu room or funeral room without mask protection ) was also assessed among all 63 exposed individuals . of them , the medical doctors and nurses ( n = 16 ) were with protection ; and the others were without ( n = 47 ) , including icu patients who were staying in the same room ( n = 8) , family members (\nn = 3 ) , and visitors to the funeral room where the corpse was kept ( n = 35 ) .\nthe multivariate analysis ( logistic regression analysis ) showed that blood contact was the most likely mode of transmission ( p < .001 ; table 1 ) .\nit is noticeable that the serum collected from the index patient on the day he died contained a relatively high amount of sftsv , which reached about 3.55 10 viral rna copies / ml ( calculated as 9.67 10 50% tissue culture infective dose [ tcid50]/ml ) .\nthis number was about 100 000-fold higher than viral copies detected in the serum samples of the 5 secondary patients , which ranged from 10 to 10 copies / ml ( table 1 ) .\nall 5 patients had virus - specific igm antibodies in the acute phase , and elevated virus - specific immunoglobin g ( igg ) antibodies in the convalescent phase . the index patient , however , had minimal or undetectable levels of virus specific igm antibodies on day 11 after onset of fever ( table 1 ) . compared with the entire genomic sequence of the virus strain isolated from the index patient ,\ncases 2 and 3 were nearly 100% identical , and provided genetic evidence for the epidemic findings on the possible transmission of sftsv from the index patient to secondary patients .\nhere , we reported the person - to - person transmission of sftsv with a cluster of 6 sfts patients that occurred in shandong province of eastern china .\ninvestigation studies revealed that all 5 secondary infected patients had possible contact with the index patient s blood .\nof them , only case 1 ( icu doctor ) had evidence of droplet contact contamination ( during intubation ) but not blood contact , but we included him also as a blood contactor because he performed intubation without protective face shield and goggles , therefore he had an extremely high risk of blood contact through unprotected skin and mucosa .\nthe risk assessment revealed that blood contact was the major risk factor for the human - to - human transmission of sftsv .\nadditionally , 3 secondary patients who only had contact with the index patient after death were still infected , which indicated that sftsv - infected blood may remain infectious for a long time , even after patient death .\nit is notable that the level of virus copies in the index patient s serum was extremely high , but with no detectable igm or igg antibodies , which suggested that his immune responses to limit the replication of sftsv were severely impaired .\nthe patient had no immune system disease , thus the minimal immune responses might be due to the early and sustained application of glucocorticoid , which has a side effect of repressing immune functions ; clinical physicians should take note of this finding .\nclinically , sfts is easily confused with hemorrhagic fever with renal syndrome caused by hantavirus and human anaplasmosis .\nthe hantavirus - specific igm antibodies were not detected in the sfts patients serum samples ( data not show ) . due to the limitation of our study , we were not able to detect rickettsia infection , which was previously reported in outbreaks of nosocomial infections\n. however , the methods we used for diagnosis of sfts patients were well validated , and the human - to - human transmission of sftsv we described in this study could not simply be classified as being nosocomial transmission ; specially , 3 of the 5 secondary cases that occurred in the household .\nadditionally , the lessons of person - to - person transmission of sftsv we learned from this study highlighted the necessity of establishing standard precautions for avoiding direct contact and blood - based transmission .\nthis work was supported by the china mega - project for infectious diseases ( 2008zx10004 - 001 , 2009zx10004 ) from the ministry of science and technology and ministry of health of the people s republic of china .\nconflicts that the editors consider relevant to the content of the manuscript have been disclosed .", "answer": "severe fever with thrombocytopenia syndrome bunyavirus is a newly discovered bunyavirus with high pathogenicity to human . \n the transmission model has been largely uncharacterized . \n investigation on a cluster of severe fever with thrombocytopenia syndrome cases provided evidence of person - to - person transmission through blood contact to the index patient with high serum virus load .", "id": 890} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe reverse shoulder arthroplasty was approved by the fda in 2004 and has proven a very effective prosthesis for treatment of cuff tear arthropathy and other shoulder conditions requiring arthroplasty in the setting of a deficient rotator cuff . however , in some series , the overall revision rate for the reverse shoulder is approximately 10% , with instability and infection being the most common precipitating causes.[13 ] studies have also shown that aseptic loosening may contribute to 7% of failures , but as indications expand and long - term follow - up increases , the incidence of aseptic loosening will likely increase .\nhave further shown that pain increases with longer term follow - up of reverse replacements ( 510 years ) .\ntherefore , in the future , surgeons will be faced with difficult choices when revising the reverse prosthesis , and optimal management of the failed reverse replacement is not known .\nwhen instability or loosening of a reverse prosthesis does occur , retention of the reverse prosthesis can be performed by ( 1 ) increasing deltoid tension with additional polyethylene or metallic spacers , ( 2 ) increasing constraint with a retentive cup or ( 3 ) revision of the humeral or glenoid components.[514 ] however , due to poor bone stock , infection or refractory instability , removal of a reverse replacement ( explant ) or conversion to hemiarthoplasty can be required .\nwe present a series of failed reverse replacements that were converted back to hemiarthroplasty with either a metallic prosthesis or preformed antibiotic shoulder spacer for infection , instability or glenosphere loosening . to date , there are few reports of reverse replacement conversion to hemiarthroplasty , and none specifically examining the shoulder function in this unique group .\nwe examine a group of patients after conversion of failed or infected reverse shoulder replacement to hemiarthroplasty ; the level of function and pain in this group is important for surgeons and patients considering a revision reverse shoulder replacement .\nfrom 2008 to 2010 , the senior author performed 115 primary and revision shoulder arthroplasty procedures . as part of the shoulder registry ( irb#10 - 000859 )\n, seven patients were identified that had presented to the senior author 's clinic with a reverse replacement that was dislocated ( 3 ) , infected ( 4 ) or loose ( 3 ) .\nall of the failed reverse replacements in this study were referred from outside hospitals for tertiary care ; revision surgery was performed an average of 9.2 months after implantation of the reverse prosthesis .\npatients with known infection were treated with explant of the reverse prosthesis using a slot osteotomy , cement extraction with an oscar device ( orthosonics , chatham , nj , usa ) and conversion mean size of the defect from 273 ( n = 3 ) ( exactech , interspace , gainesville , fl , usa ) .\nthis antibiotic spacer was cemented in place with additional antibiotic - loaded cement ( tobramycin and vancomycin ) . in three cases of gross loosening of the glenosphere\nthese patients were treated with removal of glenosphere only , bone grafting of glenoid with allograft including cancellous bone chips and demineralized bone matrix , and retention of the humeral stem by converting it via the manufacturer 's guidelines to a hemiarthroplasty ( n = 4 ) . at the time of reverse\nremoval in this elderly population , the bone stock of the glenoid was cavitary and uncontained , not deemed of sufficient quality to support immediate replacement of a single - stage revision glenosphere .\npreoperative computated tomography ( ct ) was also used in four patients to evaluate the glenoid bone stock , but was not clinically very useful due to metal artifact .\nthis group of seven patients status post removal of reverse replacement were contacted for reevaluation with physical exam and outcome scores specifically for this study .\none patient who had been converted from a dislocated , infected reverse replacement to preformed antibiotic spacer chose not to participate , but has not had any further surgery .\nthe case details of the remaining six patients who consented for examination and inclusion in this study are contained in table 1 .\ndetails of six cases of failed reverse shoulder arthroplasty converted to hemiarthroplasty using either a metallic head and retention of the reverse stem or an explant and implantation of a preformed antibiotic - loaded cement hemiarthroplasty\nthere were three males and three females ( average age 74.5 years ) who had had an average of three previous shoulder surgeries including the index reverse replacement .\nthe reverse replacement had been implanted an average of 9.2 months before failure of the prosthesis required removal .\nradiographic evidence of technical problems with the index reverse arthroplasty surgery was present in five of six cases , with superior implantation of the glenosphere ( n = 4 ) being the most common .\naverage follow - up after removal of reverse replacement was 26.5 months ( range 1041 months ) .\nthe decision to include patients with less than 2-year follow - up was made to maximize inclusion of patients that have been offered conversion back to reverse replacement .\nshoulder function was very poor postoperatively ( average forward elevation of 42.5 degrees and average external rotation near zero ) , but the pain level was generally low .\nsf-12 scores were similar to us averages in the 75 years - plus age group .\nanterosuperior escape was present in five patients ( vas instability score averaged 4.7 [ range 08 ] ) . in the sixth patient , there was static radiographic anterior subluxation ( case 1 ) .\nin the four cases where bone graft was used for glenoid deficiency , radiographic follow - up showed good incorporation of graft and reimplantation with a reverse prosthesis seemed feasible , although none of the patients elected to have this performed .\na peripherally inserted central catheter ( picc ) line was inserted and culture - specific intravenous antibiotics were administered for 6 weeks postoperatively .\nthere were no reoperations and , to date , no patient has accepted an offer to be converted back to a reverse replacement .\na 58-year - old male ( case 2 ) presented 6 months after reverse arthroplasty for failed fracture fixation with anterior dislocation of the prosthesis .\nnotice the superior placement of the glenosphere with slight superior tilt . at the time of revision surgery , no combination of glenosphere or reverse humeral component could result in stability as the prosthesis levered out with adduction past 40 degrees .\nremoval of a well - fixed glenosphere and baseplate was performed and glenoid bone stock was not sufficient for immediate revision of the baseplate to an improved position .\n( c and d ) conversion to large head hemiarthroplasty and bone grafting of glenoid defect .\ncultures were positive for p. acnes at the time of revision a 74-year - old female ( case 4 ) underwent reverse replacement for severe cuff tear arthropathy ( a ) .\nthe glenosphere loosened at 8 months postoperatively with breakage of the inferior screw ( c ) .\n( d and e ) ap and axillary views after conversion to hemiarthroplasty an 80-year - old man ( case 5 ) presented with a draining sinus and a dislocated , infected reverse replacement 6 months after primary reverse replacement at an outside institution that was complicated with reoperation the same day after a recovery room dislocation .\nglenosphere position is acceptable , but the entire humeral head was essentially resected , likely compromising stability .\n( c and d ) postoperative radiographs of preformed antibiotic spacer preoperative draining sinus an intraoperative photograph after irrigation and debridement , removal of glenosphere , slot osteotomy and cementation of preformed antibiotic spacer ( exactech interspace , gainesville , fl , usa ) with additional antibiotic - loaded cement .\nnotice how the humeral head is devoid of any soft tissue attachments creating a shoulder with profound anterosuperior escape\nin farshad and gerber 's review of reverse arthroplasty complications , they state that the optimal management for a failed reverse arthroplasty is not known and that complications that require removal of the prosthesis result in poor shoulder function .\nonce a severe complication in reverse arthroplasty is established , retention of a stable reverse prosthesis is difficult and multiple reoperations are common .\ngallo et al . reviewed a series of nine cases of reverse replacement requiring revision for instability in the setting of subscapularis deficiency .\nin these nine patients , three eventually required explant , three remained chronically dislocated and three were concentrically intact . in a retrospective review of\ndescribe their experience with dislocation and infection of reverse prosthesis . in a series of 284 reverse replacements ,\nthe rate of instability was similar in patients with primary ( 11 of 212 [ 5% ] ) and revision ( six of 72 [ 8% ] ) reverse arthroplasty . the rate of infection was higher in the revision ( five of 72 [ 7% ] ) than in the primary ( three of 212 [ 1% ] ) group . in this series\n, the authors reported that a stable noninfected prosthesis was present in only 12 of 25 shoulders revised for infection or instability , and multiple reoperations for both persistent infection and recurrent instability were common in this series . in 2008 , norris presented a series of 26 revision reverse replacements for various causes .\nnot all series of revision reverse arthroplasty have reported such a high rate of rerevision and reoperation .\nif retention of the reverse shoulder prosthesis in the setting of infection , dislocation or loosening is to be performed , the reoperation rate could be as high as 50% , and there is a potential for multiple reoperations and eventual resection arthroplasty . because of poor bone stock , persistent infection or persistent instability , conversion back to reverse replacement is not always possible in the immediate revision setting .\nin addition , due to the very elderly nature of this population and the often presence of severe medical comorbidities , a surgical strategy that could result in multiple reoperations can be unwise .\nfor this reason , conversion of the reverse replacement to metallic or cement hemiarthroplasty is an attractive option , especially in the multiply operated patient unwilling to harbor further surgical risk .\nthere seems to be less risk of reoperation using this surgical strategy , and the option remains to revise back to reverse replacement at a later date .\nhowever , successful single - stage treatment of infected and loose reverse replacements have been reported in the literature .\ngrammont revised one patient who was revised on postoperative day 1 due to an intraoperative glenoid fracture , and this patient maintained only 40 of active elevation and had persistent shoulder pain .\nfrankle reported on two patients who were converted to a hemiarthroplasty because of insufficient bone stock and a deep infection ; these patients rated the outcome of their revision as good and satisfactory . in another large series of reverse replacements ,\nsteinmann reported on a subset of four patients who were converted to a hemiarthroplasty as a result of loosening of the glenoid component in three and recurrent instability in the other .\nthree of these patients had moderate pain and one had severe persistent pain , and patient satisfaction was low .\nthis case series can be criticized for the small number of patients included and only very short - term follow - up .\nwhile the short - term follow - up may be used to predict future shoulder function , pain has been shown to increase with time .\ntherefore , it is possible that shoulder pain after hemiarthroplasty will become more significant over time , compelling patients to seek further treatment such as reimplantation of a reverse prosthesis . despite these limitations ,\nthe literature is very sparse on what comes next ? after reverse replacement .\nwe felt that this is the optimal time to report this series as it provides a snapshot of patients that are now candidates for reimplantation of reverse replacement to restore shoulder function .\nin addition , we feel that this series does provide the shoulder arthroplasty surgeon with several pieces of useful information : ( 1 ) in five of six patients , technical error was evident on postoperative radiographs with superior placement of the glenosphere often with superior tilt accounting for three cases of glenosphere loosening and one case of dislocation .\nthese technical errors likely resulted in the average failure of the index reverse replacement at 9.2 months .\n. the reoperation rate of this series will certainly increase if patients choose to have conversion back to reverse replacement .\n( 3 ) pain level was acceptable in most patients after conversion of reverse to hemiarthroplasty , with an average vas pain score of 2.4 .\n( 4 ) shoulder function was poor , with anterosuperior escape present in five of six patients .\nthis escape is likely accentuated by reversion to a state where the deltoid is again detensioned .\nfailure of reverse replacement will increase in the future , with expansion of indications to younger patients and longer term follow - up .\nthe optimal treatment for a failed reverse replacement is unknown and often very unique to each individual patient and each mode of failure .\nwhen counseling a patient with an infected , dislocated or loose reverse replacement , the patient should understand that attempts at retention and salvage of the reverse configuration of their shoulder is not always successful and can be associated with a high rate of reoperation .\nthis small series of patients shows that safe removal of a reverse replacement and conversion to hemicement spacer or hemiarthroplasty can provide the shoulder with a relatively low pain level , but that the shoulder will be nearly devoid of meaningful function postoperatively .\nevery effort should be made to meticulously assure proper initial implant placement and avoid infection in primary reverse replacement .\nin addition , when complications do occur , retention of the reverse replacement is necessary to maintain shoulder function as conversion to hemiarthroplasty results in poor function .\nthe failed reverse replacement can result in extraordinarily difficult salvage situations and therefore we echo the sentiment published by rockwood that the reverse replacement should be implanted most frequently by shoulder arthroplasty specialists prepared to treat the severe complications encountered too frequently by even the world 's experts .\nremoval of the reverse shoulder replacement and conversion to hemiarthroplasty results in a shoulder with minimal meaningful function but with an acceptably low level of pain .\nthis information can be helpful when discussing preoperatively the relative risk of revision reverse arthroplasty versus conversion to hemiarthroplasty in patients with a failed reverse replacement .", "answer": "background : the reverse total shoulder replacement has become a popular treatment option for cuff tear arthropathy and other shoulder conditions requiring arthroplasty in the setting of a deficient rotator cuff . despite a revision rate of as much as 10% , to date \n , there are few reports of reverse replacement conversion to hemiarthroplasty , and none specifically examining shoulder function.materials and methods : six patients with a reverse replacement that was dislocated , infected or loose were revised an average of 9.2 months after the reverse replacement . \n two of the three patients that were dislocated also had a known deep infection . \n patients with known infection were treated with explant of the reverse prosthesis and conversion to a preformed antibiotic spacer hemiarthroplasty . in three cases with gross loosening of the glenosphere without infection , treatment \n was performed with removal of glenosphere only , bone grafting of glenoid with allograft and conversion of humeral stem to hemiarthroplasty . \n patients were evaluated with outcome scores and physical examination an average of 26.5 months after removal of the reverse prosthesis.results:the average range of motion postoperatively was forward elevation 42.5 degrees and external rotation 1.7 degrees . \n the vas pain score was 2.42 ( range 06 ) ; simple shoulder test was 3.17 ( range 15 ) ; and ases score was 52.1 8.5 . \n there were no reoperations to date , and five patients had anterosuperior escape.conclusions:safe removal of a reverse replacement and conversion to hemicement spacer or hemiarthroplasty can provide pain relief in those patients with a dislocated or infected reverse replacement . \n however , the shoulder will likely have very poor function and anterosuperior escape postoperatively . \n further studies are needed to determine the optimal treatment for the failed reverse shoulder replacement.level of evidence : therapeutic level iv .", "id": 891} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nivm was initially introduced by pincus and enzmann ( 1935 ) , using immature rabbit oocytes capable of undergoing spontaneous maturation and fertilization in vitro .\nthe first group that succeeded in producing a child via ivm were trounson et al .\n( 1994 ) , using oocytes recovered from an untreated ovary in patients with polycystic ovaries .\nin - vitro maturation ( ivm ) has advanced significantly from its initial description to its current widespread clinical applications . despite these advances , however , there are still many controversial issues surrounding this treatment . given that ivm is an emerging protocol ( at least in humans ) ,\nthere are many controversial areas of debate , and especially regarding the subject of the best candidates for ivm ; how should we select our patients ?\nwe have conducted a review of the literature in the pubmed database from 1999 - 2013 for publications concerning the indications of ivm and examined the possibility that ivm results may be comparable to standard ivf . taking into consideration that no standard protocol exists up to present in different centres , all forms of ivf ( unstimulated , stimulated , oestrogen suppressed ) are considered together .\nseveral studies covered different indications for ivm : patients with normo - ovulatory cycles ( dal canto et al . , 2006 ; fadini et al . , 2009 ; mikkelsen et al . , 1999 , 2001 ) ,\npolycystic ovarian syndrome ( pcos ) or normo- ovulatory women with polycystic ovaries ( pco ) ( child et al .\n, 2001 , 2002 ; soderstrom - anttila et al . , 2005 ) , fertility preservation ( huang et al . , 2010 ; maman et al . , 2011 ;\n2010 ) , poor ovarian response ( ivm may serve the last choice of treatment after the failure to achieve pregnancy in traditional ivf ) ( liu et al . , 2003 ) and in rare conditions such as rescue of oocytes which have failed to mature in stimulated cycles ( tan and child , 2002 ) or cases with unexplained primarily poor quality embryos ( hourvitz et al . , 2010 ) .\nnormo - ovulatory women may be treated with ivm . since early studies , ( child et al .\n, 2001 ; mikkelsen et al . , 1999 , 2000 , 2001 ; soderstrom - anttila et al . , 2005 ) in which a 4%-25% clinical pregnancy rates were reported , there has been a constant improvement in results in normo - ovulatory patients of up to 30% pregnancy rate ( fadini et al . ,\n( 2006 ) as well suggested that ivm was a good treatment with a comparable pregnancy rate to ivf , mainly due to the italian law , which allows a maximum of three oocytes per ivf cycle and prohibits embryo or zygote ( 2pn cells ) cryopreservation .\nivm oocytes fertilize and undergo development in vitro with rates similar to in vivo matured control oocytes . in ivm cycles\nimplantation and pregnancy rates are lower compared with controlled ovarian stimulation treatments , but accurate patient selection can improve ivm clinical outcome ( fadini et al . , 2013 ) .\nthe main advantages of the ivm protocol in normo - ovulatory patients are : elimination of the side - effects of drug stimulation and reduction of the costs of the entire procedure , both in terms of time consumption and patient costs for drugs .\npcos patients are prone to develop ovarian hyperstimulation syndrome ( ohss ) with conventional ivf treatments .\na potentially useful alternative for women with pcos is earlier retrieval of immature oocytes from small antral follicles , without using hormonal stimulation , followed by ivm of those oocytes .\nsubstituting ivm in pcos patients eliminates the risk of ohss and lowers the cost of treatment . from early 2000 until the present ,\nstudies have demonstrated a encouraging pregnancy and delivery rate in pcos patients undergoing ivm treatments of 21.9%-29.9% ( child et al . , 2001 , 2002 ; ellenbogen et al .\nrecent publications report up to 32%-44% pregnancy and 22 - 29% delivery rates ( shalom - paz et al .\n, 2011 , 2012 ) , comparable with ivf pregnancy rates results of 38%-45% ( shalom - paz et al . , 2012 ) . in another study of junk and yeap ( 2012 )\nthe transfer of a single blastocyst embryo obtained after ivm in patients with pcos was proposed .\nthey obtained a live birth rate of 42.4% per oocyte collection and 45.2% per embryo transfer . in 20 oestrogen suppressed in vitro maturation cycles\nthe implantation , pregnancy and delivery rates were 17.5% , 40% and 40% respectively ( vitek et al . , 2013 ) .\nindeed sart lists higher clinical pregnancy rate for young women as > 46% in 2012 .\nhowever in europe the pregnancy and delivery rates in this group of patients undergoing icsi was 35.5% and 24.3% respectively ( ferraretti et al . , 2013 ) . de ziegler et al . ( 2012 ) opposed the need of ivm in the gnrh antagonist era .\nhowever , his results did nt take into consideration the fact that with gnrh - agonist used as a trigger to control the risk of ovarian hyperstimulation syndrome , higher pregnancy losses were observed ( humaidan et al . , 2005 ) .\non the other hand , the dual trigger approach ( gnrh - agonist + lowhcg ) revealed 2.9% of ohss complications\n( griffin et al . , 2012 ) . even applying the strategy of ovarian stimulation using the combination of gnrh antagonist with gnrh agonist to trigger ovulation and freezing all of the oocytes or embryos for later use ( devroey et al . ,\n2011 ) do not eradicated ohss totally as severe ohss after gonadotropin - releasing hormone ( gnrh ) agonist trigger and freeze - all approach in gnrh antagonist protocol was described ( fatemi et al . ,\nthe emerging technology of ivm in oocyte retrieval has recently become another option for fertility preservation .\nthis procedure can be done without hormonal stimulation and within a short time frame ; oocytes being collected during the follicular phase , within up to 13 days from cancer diagnosis and the resulting embryos either vitrified or fertilized and cryopreserved ( huang et al . , 2010 ;\n2010 ) . to shorten the period of time until cancer treatment , studies by maman et al .\ntherefore , in cases of cancer patients , especially in which hormonal treatment is contraindicated and those who must start chemotherapy without delay , ivm might be the only option to preserve fertility .\nhowever , up to now , no data are available concerning pregnancy rates in this group of patients .\none flow of ivm had been suggested , as mature eggs at retrieval often give rise to embryos that result in live birth pointing that they are not really ivm oocytes .\nhowever , from 1224 oocytes retrieved in ivm cycles only 15.6% were found mature up to six hours after retrieval vs. 64.9% that matured in vitro after 6 - 48 hours ( ellenbogen et al . , 2011 ) .\nno differences were found regarding fertilization and cleavage rates or top quality embryos developed from either oocytes ( ellenbogen et al . , 2011 ) .\n. however , soderstorm - anttila et al . ( 2006 ) showed comparable complications and malformations for babies born after undergoing ivm and ivf .\n( 2007 ) described a normal pregnancy course for ivm patients compared to ivf cycles .\n( 2012 ) reported normal growth and development of 196 babies born from ivm cycles .\nrecently , chian and cao ( 2014 ) reported 1421 healthy infants born following immature oocyte retrieval and ivm .\nthose changes are established during oocyte growth , and ivm may modify the normal maturation of the oocytes ( bao et al . , 2000 ) . moreover ,\nmay have deleterious effects on the organization of the meiotic spindle and chromosome alignment of human oocytes .\nthis finding may be a possible explanation for the reduced developmental potential of oocytes matured in vitro compared with those matured in vivo ( li et al . ,\nhowever despite the great achievements obtained in treating infertile couples by standard ivf during the last 34 years , it has become evident in recent years that ovarian stimulation , although a central component of ivf , may itself have detrimental effects on oogenesis , with production of aneuploidity ( baart et al . , 2007 ) , reduced embryo quality , lower endometrial receptivity and perhaps also perinatal outcomes ( santos et al . , 2010 ) .\nin vitro maturation of oocytes is a simple procedure . it is an economical and less stressful procedure for women .\npuncture is simple and safe and it can improve the disrupted endocrine environment and induce a spontaneous recovery of ovulation and pregnancy in women with pcos without other infertile factors . it can avoid short - term complications , such as ovarian hyperstimulation syndrome and possible long - term complications , such as hormone dependent neoplasm s including breast and ovarian cancers .\nstudies to date have not identified an alarming rate of congenital anomalies in ivm children , and studies which have followed up children to the age of 2 years old have provided reassuring results regarding their growth and development .\nivm holds great promise as an alternative to assisted reproductive technologies and may be the procedure of choice not only for infertile patients but also for obtaining oocytes for donation or fertility preservation .\nimproving embryonic - endometrial synchrony through pharmaceutical or other manipulation of endometrial / uterine receptivity will hopefully result in future improvements in ivm success rates .\nproper counselling of these patients about advantages and disadvantages of the procedure should be performed routinely .\nthe goal of the art is to help patients fulfil their most basic desires of reproduction and continuity , using technology that was only imaginary not long ago .\nthese techniques are not yet flawless and may be associated with taking some calculated risks and courageous decision making , without which we would never have been able to help so many people and create so many happy families .", "answer": "retrieval of immature oocytes from unstimulated ovaries , followed by in vitro maturation ( ivm ) was originally proposed in order to avoid side effects of gonadotropin administration . \n the target is to eliminate or significantly reduce the risk of ovarian hyperstimulation syndrome ( ohss ) in patients with polycystic ovary syndrome ( pcos ) , drug cost and burden on patients . \n this technology was also suggested in treatment of normo - ovulatory women , fertility preservation or infrequent conditions such as failure of oocytes to mature or repeated development of poor quality embryos . in this study \n we intended to examine the possibility that ivm results may be comparable to standard ivf . a pubmed database search from 1999 - 2013 was carried out for publications concerning the indications of ivm and study the possibility that ivm results may be comparable to standard ivf.in vitro maturation of the oocytes procedures obtained up to 35% clinical pregnancy rate in young women , comparable with in vitro fertilization ( ivf ) in many programs . \n the obstetric and perinatal outcomes of ivm cycles are comparable with ivf / icsi cycles.in conclusion ivm may gradually replace ivf in certain cases , as the technique continues to develop and pregnancy rates continue to increase , being a promising and simple alternative approach to standard ivf in various indications .", "id": 892} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchikungunya ( chikv ) and dengue ( denv which is divided into 4 serotypes , 1 to 4 ) viruses are both arthropod - borne viruses belonging respectively to the genus alphavirus , togaviridae family and flavivirus , flaviviridae family , and transmitted to humans via a bite of infected aedes mosquitoes ( aedes aegypti , aedes albopictus ) . over the past two decades , they have caused multiple worldwide outbreaks , particularly in tropical and sub tropical areas .\nrecent chikv outbreaks started in kenya in 2004 , spread over the indian ocean region , reached india causing in all more than 1.5 million cases .\nthen , numerous imported cases were reported in different parts of the world , an outbreak occurred in italy , while autochthonous cases were reported in france .\nin central africa , outbreaks occurred in democratic republic of congo , cameroon , gabon and republic of congo .\nas for dengue fever ( df ) , its incidence has grown dramatically around the world , rising more than 30-fold in recent decades .\ntwo fifths of the world 's population are at risk of infection , and who currently estimates there are 50 million dengue infections each year .\nthe disease is now endemic in more than 100 countries in africa , the americas , the eastern mediterranean , south - east asia and the western pacific . during the last decade ,\ndenv epidemics have occurred in some east and west african countries , including cape verde where more than 17,000 df cases due to serotype 3 were notified . in practice ,\nthe global picture of both chikungunya and df is similar in their classical forms , so they can be confused particularly in areas where they cocirculate . after variable incubation period ,\nboth diseases start abruptly with acute fever , arthralgias , myalgias , headaches , rash and fatigue .\narthralgias are often incapacitating in chikv infection and can persist for several years in some patients . for denv infection , after the initial febrile phase , hemorrhagic manifestations can occur , leading to dengue hemorrhagic fever ( dhf ) indeed dengue with shock syndrome ( dss ) . and finally , in addition to denv , reports of deaths in la reunion island were directly attributed to chikv .\nfurthermore , there is no comparative study of the two infections , still lesser in a concurrent outbreak . here\n, we compare the clinical features and the laboratory findings for 343 laboratory - confirmed patients from the concurrent chikv / denv outbreak which occurred in gabon in 2010 .\nfranceville , the main town of the haut ogooue province , 512 km south - east from libreville ( capital of gabon ) , is located at altitude 333 meters , at the end of the transgabon railway and the national 3 road , in a savannah ecosystem constituted by forest gallery ( figure 1 ) .\nthere are 5 health care capacities ( hcc ) including 2 public hospitals with 170 beds in all and the medical unit of the centre international de recherches medicales de franceville ( cirmf ) .\na concomitant chikv/ denv outbreak raged 11 towns and one village of the southeast , from february to july 2010 , and recorded 1127 laboratory confirmed cases in franceville .\nthe cirmf was included as a partner of the moh , in the response to this outbreak , and implicated in active surveillance , case management and diagnostic . as part of these activities ,\na prospective study was initiated , and the investigations were considered as a component of the public health response and authorized by the regional health director . \n\nmap of gabon with location of the gabonese chikungunya outbreak in 2010 . at the time of the outbreak ,\nthe moh provided a case definition including 2 categories : a suspected case was a patient presenting with at least one of the following symptoms : fever , arthralgias , myalgias , headaches , rash , fatigue , nausea , vomiting , diarrhea , bleeding , and jaundice ; a confirmed case was a suspected case with laboratory confirmation .\nall suspected cases consulting in the cirmf medical unit were examined and demographic and clinical data collected in standardized questionnaire .\nblood samples were collected in two 7-ml edta vacutainer tubes and one 7-ml dry tube ( vwr international , france ) .\nthe tubes were stored in the dark at + 4c until arrival at the laboratory .\nthick and thin blood films were stained with 20% giemsa and examined for malaria parasites .\nhematological ( hematology analyser act 10 , beckman coulter ) and biochemical ( creatinine , ast , alt ) tests were performed ( automatic analyser hitachi model 902 , roche diagnostics ) .\nsamples were tested for chikv and denv rna genomes by using taqman qrt - pcr technology and specific primers and probes . when used during the acute phase ( 17 days after onset of symptoms ) , the taqman qrt - pcr technology has a sensitivity of up to 80% and specificity of 100% .\nresults were expressed as averages ( with their sd ) and percentages ( with their 95% confidence interval , ic ) .\nthe student 's t test was used to compare laboratory parameters and continuous clinical variables . for qualitative variables , the chi square test or fisher 's exact test were used as appropriate .\nfranceville , the main town of the haut ogooue province , 512 km south - east from libreville ( capital of gabon ) , is located at altitude 333 meters , at the end of the transgabon railway and the national 3 road , in a savannah ecosystem constituted by forest gallery ( figure 1 ) .\nthere are 5 health care capacities ( hcc ) including 2 public hospitals with 170 beds in all and the medical unit of the centre international de recherches medicales de franceville ( cirmf ) .\na concomitant chikv/ denv outbreak raged 11 towns and one village of the southeast , from february to july 2010 , and recorded 1127 laboratory confirmed cases in franceville .\nthe cirmf was included as a partner of the moh , in the response to this outbreak , and implicated in active surveillance , case management and diagnostic . as part of these activities ,\na prospective study was initiated , and the investigations were considered as a component of the public health response and authorized by the regional health director . \n\nat the time of the outbreak , the moh provided a case definition including 2 categories : a suspected case was a patient presenting with at least one of the following symptoms : fever , arthralgias , myalgias , headaches , rash , fatigue , nausea , vomiting , diarrhea , bleeding , and jaundice ; a confirmed case was a suspected case with laboratory confirmation .\nall suspected cases consulting in the cirmf medical unit were examined and demographic and clinical data collected in standardized questionnaire .\nblood samples were collected in two 7-ml edta vacutainer tubes and one 7-ml dry tube ( vwr international , france ) .\nthe tubes were stored in the dark at + 4c until arrival at the laboratory .\nthick and thin blood films were stained with 20% giemsa and examined for malaria parasites .\nhematological ( hematology analyser act 10 , beckman coulter ) and biochemical ( creatinine , ast , alt ) tests were performed ( automatic analyser hitachi model 902 , roche diagnostics ) .\nsamples were tested for chikv and denv rna genomes by using taqman qrt - pcr technology and specific primers and probes . when used during the acute phase ( 17 days after onset of symptoms )\n, the taqman qrt - pcr technology has a sensitivity of up to 80% and specificity of 100% .\nresults were expressed as averages ( with their sd ) and percentages ( with their 95% confidence interval , ic ) .\nthe student 's t test was used to compare laboratory parameters and continuous clinical variables . for qualitative variables , the chi square test or fisher 's exact test were used as appropriate .\nthe sex ratio m / f was 0.99 and the mean age was 3015 ( range , 177 years ) . among these 433 patients ,\n343 ( 79.2% ) were laboratory confirmed with 270 ( 62.3% ) chikv+ , 53 ( 12.2% ) denv+ .\nthe sex ratio m / f was 0.85 for the chikv group , 0.55 for the denv group and 1 for the chikv / denv group , and the mean age was respectively 3016 ( range 1 77 years ) , 3114 ( range , 576 years ) , and 3612 ( range , 174 ) .\nhospitalization was required for 39 ( 14.4% ) chikv+ , 2 ( 3.7% ) denv+ ( p=0.02 ) , and 6 chikv / denv+ patients .\nheadaches and hemorrhage were more frequent ( p respectively 0.01 and 0.001 ) in the denv+ group than in the chikv+ group ( table 1 ) , and myalgias were more frequent in the chikv and denv groups than in the chikv / denv group ( p = 0.005 and 0.02 respectively ) .\nsimilarly , leukopenia and lymphopenia were more frequent ( p respectively 0.02 and 0.001 ) in the denv+ group than in the chikv+ group ( table 2 ) .\nthere was no difference in biological parameters between the co - infected group and the other groups . \n\ntable 1comparison of clinical signs between chikungunya and dengue - infected patients during the 2010 outbreak in gabon.chikv+denv+pn%n%hospitalization3914.323.60.02clinical symptomsfever234865292.90.16arthralgia22783.54783.90.93myalgia19571.74071.40.96headache19069.94885.70.01asthenia21478.74478.60.72skin rash11140.81526.80.06pruritus7326.81119.60.26digestive signs87321934.50.86hemorragy51.8712.50.001chikv , chikungunya virus ; denv , dengue virus . \n \ntable 2comparison of biological parameters between chikungunya and dengue - infected patients during the 2010 outbreak in gabon.chikv+denv+pmeansdmeansdbiological parametershaemoglobin12.31.711.91.140.49leucocytes52431676339015170.02lymphocytes222821614012430.001platelets23308981750225600608240.77asat171118100.38alat453550340.58cratinine963288320.14chikv , chikungunya virus ; denv , dengue virus . \n \nwe conducted a comparative study of clinical and biological data of patients with chikungunya and dengue viruses infections during a concurrent outbreak which occurred in south east gabon in 2010 .\nof the 343 individuals included in the study , 270 were chik+ , 53 were denv+ , and 20 were co - infected ( chik+/den+ ) .\nheadaches , hemorrhage , leukopenia and lymphopenia were significantly more frequent in denv+ patients . in our opinion ,\nthus , the circulation during this epidemic of other arboviruses such as west nile , rift valley fever and yellow fever viruses , can not be ruled out . to our knowledge , this is the first comparative study of these two diseases .\n, chikungunya is described in the literature as a dengue - like disease , due to their common symptoms .\nnevertheless , the existence of incapaciting joints pain located at the extremities seems specific of chikungunya .\nthis distinction is difficult in tropical areas where many other diseases , such as malaria , typhoid fever , influenza , share the same symptoms .\nso , in our field experience , these diseases are clinically indistinguishable , and the problem of differential diagnosis may be compounded during concomitant chikv / denv outbreaks in a malaria endemic area . in their classical form , the hemorrhage constitutes an inconstant sign .\nbleeding is generally minimal , non life - threathning , and can not assist for the differential diagnosis .\nthis entity is more recognizable , leading , with the shock syndrome , to the severity of the disease .\nthese hematological disorders are non specific and can not also assist for the differential diagnosis .\npatients with mixed infection did not seem to have more severe symptoms or biological disorders , suggesting no additive effect of the two viruses .\nthe clinical and biological differences detected in our analysis are not useful in the field .\nso , our study confirms that the two diseases are clinically similar and need for laboratory confirmation for their recognition . since their appearance in 2007 in the north of the country , these viruses have spread in the south east , together with the vector aedes albopitus .", "answer": "chikungunya ( chikv ) and dengue ( denv ) viruses , both arboviruses , have caused multiple outbreaks worldwide . \n their clinical features are poorly described in africa and there is no comparative study , although chikungunya is considered as a dengue - like disease . \n we conducted a comparative study of clinical and biological data from chikv and denv positive patients during the 2010 gabonese outbreak . \n patients consulting with general symptoms and having laboratory confirmation for chikv or denv were included . \n clinical and biological data were recorded . \n statistical analyses were performed using epi info . \n a p value < 0.05 was considered significant . in all , 270 chikv+ , 53 denv+ and 20 co - infected patients were included in the study . \n headaches , hemorrhage , leukopenia and lymphopenia were significantly ( p respectively 0.01 , 0.001 , 0.02 and 0.001 ) more frequent in denv+ patients than in chikv+ . \n there was no additive effect of the two viruses.these clinical and hematological disorders are non specific and can not assist for the differential diagnosis . \n these diseases are clinically indistinguishable , and need for laboratory confirmation .", "id": 893} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin the previous issue of critical care , rhodes and colleagues report on significantly increased levels of circulating dna in patients admitted to the intensive care unit ( icu ) in comparison with healthy controls .\nthey show plasma dna levels to be an independent predictor of mortality and the development of sepsis in these patients . in sepsis and trauma , circulating nucleosomal dna is positively correlated with disease severity and adverse outcome . in cancer ,\ninterestingly , in systemic lupus erythematosus , an autoimmune disease in which nucleosomal dna functions as autoantigenic target , no correlation of circulating nucleosomal dna with disease severity can be found ; instead there is a correlation with anti - nucleosomal dna antibodies .\ndna in plasma most probably circulates bound to proteins in the form of mononucleosomes and/or oligonucleosomes and is released after the cleavage of easily accessible linkage sites of cellular dna by endonucleases after cell death .\na mononucleosome consists of a core particle composed of an octamer of two copies each of histones h2a , h2b , h3 and h4 , around which a stretch of helical dna 146 base pairs in length is wrapped .\noligonucleosomes are composed of variable amounts of mononucleosomes connected by intact linker dna with a variable length of 15 to 100 base pairs containing a ' linker ' histone h1 . once released into the circulation , nucleosomes seem to be protected by their structure from further degradation by endonucleases . in healthy individuals ,\nthe concentration of circulating dna is low , because dead cells are removed efficiently from circulation by phagocytes .\ncirculating dna has a short half - life ( 10 to 15 minutes ) and is removed mainly by the liver .\naccumulation of dna in the circulation can result from an excessive release of dna caused by massive cell death , inefficient removal of the dead cells or a combination of both .\nrhodes and colleagues demonstrate that increased circulating dna not only predicts the development of sepsis but also mortality in patients admitted to the icu .\nmoreover , they show that patients requiring renal support have significantly higher values of circulating dna than patients with sufficient renal function .\nunfortunately , the authors provide no information on liver function , because most nucleosomal dna is efficiently cleared by the liver and only a small fraction is eliminated by the kidney .\nour recent study in patients with sepsis showed that nucleosomal dna increased with disease severity , but we found no difference in nucleosome levels in patients with severe renal insufficiency and normal renal function , respectively .\nother studies in patients with trauma and stroke showed that increased circulating dna levels were correlated with morbidity and mortality .\nhence , assessment of circulating dna offers a useful tool for predicting mortality and morbidity of patients admitted to the icu .\nfurther studies on circulating dna in icu patients , including more patients and other scoring systems for illness severity such as saps ii ( simplified acute physiology score ii ) , logistic organ dysfunction and apache ii ( acute physiology and chronic health evaluation ii ) scores , are needed to establish circulating dna as a predictor for mortality and morbidity in patients admitted to the icu .\nquantification of circulating nucleosomes can be assessed either by real - time quantitative pcr ( rq - pcr ) or immunological assays .\nhowever , contamination of a sample with nucleated cells can affect the apparent concentration of circulating dna .\nchiu and colleagues showed that a two - step procedure of sample centrifugation ( 800 g or 1,600 g ) followed by either high - speed centrifugation or filtration was superior to a single centrifugation step only .\nnevertheless , a 13.5-fold variation in circulating dna levels over 3 days can be detected in female volunteers .\ntherefore , even though an appropriate sample preparation protocol may be used , notable variation requires a careful interpretation of circulating dna levels .\nnucleosomal dna can also be assessed by elisa technique as recently described by different groups . in our laboratory\nwe developed an elisa with the use of a mouse monoclonal anti - histone 3 antibody ( clb - ana/60 ) as a catching antibody and a monoclonal mouse antibody recognizing an epitope exposed on complexes of histone h2a , histone h2b and double - stranded dna , present only on nucleosomes , as a detection antibody .\nthis technique renders quantitative determinations reliable and reproducible . also with elisa , careless blood withdrawal and delayed centrifugation\ncan result in false positive results , and insufficient storage conditions can lead to false negative results . moreover , sandwich elisas are vulnerable to false positive results resulting from xenoantibodies , c1q , rheumatoid factors and anti - nucleosome antibodies ( l aarden , unpublished work ) . a comparison of rq - pcr and elisa methods revealed a high concordance in the quantification of circulating dna in plasma and serum .\nquantification should preferably be performed in plasma because , probably as a result of the clotting process , higher levels of circulating dna can be measured .\nhowever , determination of circulating dna by rq - pcr seems to be more sensitive than by elisa .\nthe lowest circulating dna level measured by rq - pcr in the present study was 14 ng / ml , which corresponds to 2,121 genome - equivalents / ml ( assuming a dna content of 6.6 pg per cell ) . however , circulating dna can be detected by rq - pcr up to 2 genome - equivalents / ml . in our recent study on nucleosome levels assessed by elisa , we reported a detection limit of 35 units / ml , which corresponds to 3,500 cells / ml .\nfurther improvement of the assay improved the detection limit to 1,000 cells / ml . fully automated systems in dna isolation , pcr mixture preparation and rapid thermal cycling profile offer a quick and sensitive tool for quantifying circulating dna in plasma .\nhowever , these systems require considerable amounts of plasma : reliable dna extraction for rq - pcr requires at least 200 l of plasma , whereas only 25 l suffices for elisa .\nassessment of circulatory dna is a useful tool for predicting morbidity and mortality in patients admitted to the icu .\nelisa = enzyme - linked immunosorbent assay ; icu = intensive care unit ; lod = logistic organ dysfunction ; rq - pcr = real - time quantitative polymerase chain reaction .", "answer": "in various diseases , such as cancer , autoimmune disease , sepsis or myocardial infarction , elevated levels of circulating dna can be measured . however , its predictive value is under debate . circulating dna in plasma is protein - bound ( nucleosomal ) dna . \n quantification of circulating dna can be performed by real - time quantitative pcr or immunological methods such as elisa . \n the diagnostic value of both methods can be impaired by inappropriate handling of the samples . \n assessment of circulating dna in patients admitted to the intensive care unit offers a tool for predicting morbidity and mortality .", "id": 894} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntwenty - one animals ( 16 cattle and 5 sheep ) showing clinical signs suggestive of bluetongue were sampled by the federal agency for the safety of the food chain on august 18 , 2006 , at 11 farms in northeastern belgium . two serologic tests that detect antibodies against the major serogroup antigen vp7 ( bluetongue virus antibody competitive elisa [ celisa ] ; veterinary medical research and development inc . ,\npullman , wa , usa and competitive vp7 bluetongue kit ; idvet , montpellier , france ) identified 21 virus - positive animals .\ntwo newly developed and validated reverse transcription quantitative pcrs ( rt - qpcrs ) that detected btv strains representing the 24 serotypes ( 4 ) were then conducted to determine whether these seropositive animals also had viral rna . the first assay ( rt - qpcr_s1 ) , which amplified a 357-nt fragment in segment 1 , detected virus in erythrocytes of the 21 seropositive animals ( mean cycle threshold [ ct ] value 29.0 ) . the second assay ( rt - qpcr_s5 ) , which amplified a 94-nt fragment in segment 5 , detected virus in the same 21 seropositive animals ( mean ct value 26.5 ) . the 2 serologic tests and the 2 molecular assays detected btv in 21 animals from 11 belgian farms within 14 hours .\nvirus isolation was conducted on august 18 , 2006 , by injection of blood from infected sheep into 11-day - old embryonated chicken eggs , followed by passage on bhk-21 cells ( atcc - ccl10 ) as previously described ( 5 ) .\nthe specificity of the cytopathic effect observed 48 hours after passage on bhk-21 cells was confirmed by rt - qpcr and electron microscopy ( figure 1 ) after fixation and negative staining as previously described ( 6 ) .\ntwo virus neutralization tests were conducted on 2 virus strains isolated by the belgian and the french reference laboratories at 2 belgian farms 30 km apart .\neach strain was also partially neutralized by reference serum against serotype 18 , which confirmed cross - neutralization between serotypes 8 and 18 ( 7 ) .\nto september 14 , 2006 , the study farms were screened for animals with clinical signs of bluetongue .\nblood samples were tested by serologic tests or rt - qpcr . for cattle , 97 ( 68% ) of 142 samples had antibodies to btv and 32 ( 78% ) of 41 samples contained viral rna ( table 1 ) . however , for sheep , only 23 ( 29% ) of 79 samples had antibodies to btv and 15 ( 45% ) of 33 samples contained viral rna . other diseases that cause similar signs might explain this lower frequency in sheep .\ncontagious ecthyma was diagnosed by using pcr and electron microscopy for several sheep that showed bluetonguelike signs but did not have antibodies to btv or viral rna .\nagreement between celisa and rt - qpcr results was analyzed for 124 animals ( table 2 ) .\none sample negative by rt - qpcr_s1 and rt - qpcr_s5 was positive by celisa .\nalthough this result might reflect lack of specificity of the celisa , elimination of btv rna from the animal several weeks after being infected can not be ruled out .\na false - negative result in the rt - qpcr is unlikely because 1 ) 2 different rt - qpcrs that amplified 2 different segments were used , 2 ) the quality of the rna was confirmed by a third rt - qpcr that quantified mrna of -actin , and 3 ) both rt - qpcrs are highly sensitive ( they can detect 0.01 infectious doses of virus ) ( 4 ) .\nfalse - positive results were not observed with the idvet celisa when we analyzed 650 negative serum samples from artificial insemination centers and field samples collected from belgian livestock in 2004 and 2005 .\nseven animals with bluetonguelike clinical signs were positive according to each rt - qpcr but negative according to the celisa ( table 2 ) .\nthese results support the finding that rt - qpcr can be used to detect viral rna in infected animals before antibodies are detectable .\ncelisa , competititve elisa ; rt - qpcr , reverse transcription quantitative pcr . \nsamples with different results in celisa and rt - qpcr_s5 were retested with rt qpcr_s1 ( 4 ) .\nthis latter test always confirmed the result of the rt - qpcr_s5 . on september 14 , 2006 ( 4 weeks after the first identification of btv in belgium ) as many as 84 belgian farms had at least 1 btv - infected animal .\nthe maximal distance between herds in this study was 110 km ( figure 2a ) .\nmost outbreaks were confirmed in the area where the disease was initially detected ( area i , figure 2 ) .\nmost ( 64% ) infected animals showed a high virus load with individual ct values < 30 .\nof the remaining animals , 30% had moderate virus loads ( ct values 3035 ) and 6% had ct values > 35 .\nthe high ct values for the latter animals might have remained undetected had pooled blood samples been analyzed .\nthus , results of pooled samples need to be validated before being used for diagnosis .\nnone of the animals from zones iii and iv showed a ct value < 30 , whereas all animals from zone ii showed low ct values , which are indicative of high virus loads .\nlower virus loads and acute clinical signs in animals from zones iii and iv might indicate onset of infection . however , we can not rule out decreased infection in these animals because they also had positive serologic results that indicated infection for at least 45 days .\nfurther epidemiologic studies are required before conclusions can be drawn on the evolution of these epidemics .\na ) distribution of outbreaks of bluetongue ( shaded areas ) reported in belgium from august 18 through september 14 , 2006 .\nb ) cycle threshold ( ct ) values observed in different zones as a result of conducting reverse transcription \nbtv has been detected and its isolation and characterization have considerably progressed in the first weeks of the epidemics .\nresults of virus neutralization tests for 2 belgian isolates and molecular characterization of the dutch btv strain by the community reference laboratory ( 8) indicate that btv serotype 8 is present in belgium and the netherlands .\nalthough this observation suggests 1 serotype circulating in northern europe after a common virus introduction , it must be confirmed by detailed epidemiologic studies .\nnorthward spread of bluetongue in europe has been correlated with climate warming ( 9 ) . however ,\none characteristic of the current epidemics of bluetongue is the severity of clinical signs reported in cattle ( 10 ) .\nthe present results also demonstrate that clinical signs observed in cattle are more specific than those observed in sheep . confusing clinical signs in sheep\nunderline the need for developing diagnostic tests to discriminate between bluetongue and other confounding diseases such as contagious ecthyma , border disease , and foot - and - mouth disease .\nour results also indicate the usefulness of rt - qpcr , which detected viral rna in recently infected animals with clinical signs of bluetongue but no detectable antibodies to btv .\nthe rt - qpcr and elisa are independent but complementary tests because they detect viral rna and virus - specific antibodies , respectively .\nthese tests indicated that an outbreak of bluetongue was occurring in belgium . despite high sensitivity of rt - qpcr ( 4 )\n, our results suggest that using this test with pooled samples might not detect animals with low viral loads .\nrt - pcr positive results in animals that are no longer infectious ( 11 ) should also be considered before deciding whether pooled samples are acceptable .", "answer": "bluetongue has emerged recently in belgium . a bluetongue virus strain was isolated and characterized as serotype 8 . \n two new real - time reverse transcription quantitative pcrs ( rt - qpcrs ) that amplified 2 different segments of bluetongue virus detected this exotic strain . \n these 2 rt - qpcrs detected infection earlier than a competitive elisa for antibody detection .", "id": 895} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nindications for covered self - expandable metallic airway stent removal include recurrent mucous plugging of the stent , excessive or recurrent granuloma formation , migration of the stent , stent infection , recurrence of stenosis , stent failure , stent fractures and accomplishment of treatment . usually , it is tedious to remove a stent because of their embedding in the bronchial mucosa and epithelization of the inner surface .\ngranuloma formation at the extremities is a relative common occurrence in covered metallic stents possibly resulting from the radial force applied against the airway wall and the friction exerted .\nwe report a case of covered self expandable metallic stent removal with a rigid bronchoscope under general anesthesia .\nthe case is unique because it had almost all the common complications associated with the stent placement but it was successfully removed without much ado . to the best of our knowledge\nthis is the first case of successful removal of a complete stent reported from india .\na 21 year old female presented with complaints of increasing dyspnoea and cough with pain chest for last two weeks .\npatient had a past history of benign tracheal stenosis which was opened up by endobronchial electro surgery followed by placement of a self expandable metallic airway covered stent .\nx - ray chest done one and a half year back showed stent well in place [ figure 1 ] .\nx - ray chest done one and a half year back showing stent well in place bronchoscopy was done under local anesthesia and a stenosis was observed well above the level of the stent [ figure 2 ] with granulation tissue inside the stent [ figure 3 ] , lower end of the stent was fractured , carina was not visualized and stent was seen entering upper part of right main bronchus [ figure 4 ] .\nthe beveled edge of the rigid scope was advanced between the stent wall and the airway mucosa thus creating a space between them .\nthe circular extraction loop at the upper end of the metallic stent was grasped with a rigid optical alligator forceps and pulled in the lumen of rigid bronchoscope with continuous winding movements gradually separating the stent from the tracheal wall . immediately after that\nthis is one of the rare cases of successful removal of self expandable metallic airway covered stent in benign tracheal stenosis .\nstenosis above the level of the stent granulation tissue inside the stent and at the margins fracture of stent at its lower end ( stent is seen at upper part of right main bronchus , carina is not visualized ) the stent after removal\nthe management of patients with tracheal / bronchial strictures of benign etiology can be quite challenging .\nthough surgical tracheal sleeve resection and reconstruction remains the gold standard for most benign airway strictures , non - surgical modalities such as laser photocoagulation and resection , balloon dilatation , electrocautery and stenting of the airway have been developed to deal with airway stenosis .\nvarious inoperable benign airway disorders are considered for airway stenting , like post intubation tracheal stenosis , tracheal burn or trauma , tracheo - broncho - malacia and extrinsic compression of trachea . though silicone prostheses are considered to be first choice in benign diseases\ntheir use is less suited , especially in airway wall malacia or distal and angular stenosis where sems are preferred .\nthe disadvantages of the silicone stents are high migration rate , small lumen to wall thickness ratio and difficulty in clearing the secretions . on the other hand\n, the major drawback for placement of sems in benign situations is their difficult repositioning and removal in situations like excessive granulation tissue , stent fractures and stent migration .\nthe complications of stent removal include significant oozing , tracheal mucosal dehiscence , tracheal puncture requiring thoracotomy , retained stent pieces , need for restenting , respiratory failure , tracheotomy , and even death . in our case ,\nvarious authors have come up with different methods of removal of the stent , like the technique of nashef et al . , which was similar to that of rolling spaghetti on a fork , but much more difficult and at least equally messy .\nthey further observed that there may be several fractures of the stent , which have to be removed piece by piece . in our case\nfiller et al . , used a metal suction catheter to dissect the stent from the airway wall before extraction with the forceps .\nzakaluzny et al . , employed a rigid suspension laryngotracheoscope and used optical forceps to dissect the stent from the airway wall .\nalligator forceps were then employed to grasp and extract the stent through the rigid scope while the scope was advanced further into the airway .\nwe first separated the stent from the tracheal wall and then removed all the works ( scope , forceps and the stent ) in one piece .\nto conclude , this case is unique for many reasons , firstly , it had almost all of the complications that can be associated with stent placement ( stenosis of trachea at the upper end of the stent , extensive granuloma formation , migration of the stent downwards and fracture of the stent at its lower end ) , secondly , we were able to remove the stent in toto [ figure 5 ] and lastly , there were no complications after removal of the stent .\nfurther studies are needed to re evaluate their removal successfully and safely and to produce better designed and technically superior stents like bio - absorbable stents which may not have to be removed at all .", "answer": "covered self expandable metallic airway stents ( sems ) have been used for benign tracheal stenosis , post intubation tracheal stenosis , tracheal burn or trauma , tracheo - broncho - malacia , and extrinsic compression of trachea . \n their placement is considered to be permanent , with open surgery the only way to remove the stent , though there are few cases reports of their removal with the bronchoscope , but the complications after their removal are very high . in our patient , one and a half years after placement of sems , she developed cough with dyspnoea , video bronchoscopy showed stenosis above the level of stent with granulation tissue inside the stent , stent fracture in lower part and stent migration to right main bronchus , thus she had all conceivable complications of stent placement . \n the stent was removed with the help of rigid bronchoscope under general anaesthesia . \n she was discharged the following day . \n the case is being reported because it was unique in having all the possible complications of stent placement , and rare as we could take out the stent in toto . \n thirdly , the stent could be removed without any complication .", "id": 896} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndipeptidyl peptidase4 ( dpp4 ) inhibitors improve glycemic control in patients with type 2 diabetes by preventing degradation of two incretin hormones , glucagonlike peptide1 ( glp1 ) and glucosedependent insulinotropic polypeptide ( gip ) , that are secreted from the intestine on ingestion of various nutrients .\nrecent studies have shown associations of dpp4 inhibitors efficacy with age and fasting plasma glucose levels , as well as baseline glycated hemoglobin ( hba1c ) and body mass index ( bmi ) , but clinical parameters that predict the efficacy of dpp4 inhibitors are largely unknown .\nthe present study showed that alterations in hba1c level on administration of dpp4 inhibitors as monotherapy are associated with estimated intake of fish , estimated intake of dietary n3 polyunsaturated fatty acid ( pufa ) , and serum levels of eicosapentaenoic acid ( epa ) and docosahexaenoic acid ( dha ) .\nthe protocol was approved by the ethics committee of kansai electric power hospital , and carried out in accordance with the principles of the declaration of helsinki . a total of 72 untreated japanese patients with type 2 diabetes ( the japan diabetes society criteria of 2010 ; age 64.6 11.3 years ; duration of diabetes 9.0 8.9 years ; baseline hba1c 7.2 0.7% ; bmi 24.5 4.3 kg / m ) who had been on diet and exercise therapies participated in the current study .\ndpp4 inhibitors ( sitagliptin , alogliptin or vildagliptin ) were given for 4 months and no other antidiabetic drugs were used during the period .\na total of 59 patients received sitagliptin , 12 received alogliptin and one received vildagliptin .\nhba1c levels were determined before the initiation of dpp4 inhibitors and 4 months after the initiation of dpp4 inhibitors , and were shown in national glycohemoglobin standardization program values , as recommended by the japan diabetes society . fasting serum levels of dha , epa and arachidonic acid ( aa ) were determined based on fatty acid composition of total lipids including phospholipids , triglycerides and cholesteryl esters in the serum of 20 patients ( age 63.1 11.7 years ; duration of diabetes 6.7 5.7 years ; baseline hba1c 7.0 0.8% ; bmi 24.2 3.1 kg / m ) before initiation of dpp4 inhibitors .\nselfadministered 3day food records , which were recorded during the 4month period , were analyzed for estimated intake of various nutrients using healthy maker pro 501 ( mushroomsoft co. , ltd . ,\nall statistical calculations were carried out using pasw statistics 18 ( sas institute inc . ,\ncary , nc , usa ) , including linear regression analyses of the associations between changes in hba1c levels and various parameters .\nmultiple linear regression analyses were carried out to identify the parameters potentially associated with hba1c reduction , and simple regression analyses were carried out to evaluate their contributions .\nin the present study , dpp4 inhibitors , similarly to previous reports , significantly reduced hba1c levels , but not bodyweight ( before initiation of dpp4 inhibitors 7.2 0.7% ; 4 months after initiation of dpp4 inhibitors 6.7 0.6% [ paired ttest , p < 0.01 vs before ] ) .\nmultiple regression analysis of hba1c reduction ( hba1c ) taking into account sex , age , duration of diabetes , bmi , baseline hba1c and estimated intake of various food categories in 3day food records showed that hba1c was well correlated with baseline hba1c , but not with bmi ( table 1 ) .\nhba1c also showed a significant association with estimated intake of fish and seafood in the food records ( figure 1a and table 1 ) . among fish and seafood , estimated intake of fish , but not shellfish and other seafood , showed a significant association with hba1c ( table s1 ) .\nthe beneficial effects of fish on human health have been partly attributed to pufa , such as epa and dha .\nhba1c was significantly correlated with estimated intake of epa and dha , along with baseline hba1c ( figure 1b and table s2 ) . as\nserum epa and dha levels might serve as markers for intake of corresponding fatty acids ( figure s1 ) , we analyzed associations of hba1c with serum epa and dha levels .\nserum levels of epa and dha , but not n6 pufa arachidonic acid , were well correlated with hba1c ( figure 1c ) .\nalthough hba1c reduction showed a significant association with estimated intake of milk products ( table 1 ) , we were unable to find nutrients in milk products , including saturated fatty acids , that were responsible for the association .\nmultiple regression analysis regarding changes of glycated hemoglobin ( hba1c ) levels ( hba1c ) by taking into account sex , age , duration of diabetes , body mass index ( bmi ) , baseline hba1c ( national glycohemoglobin standardization program [ ngsp ] ) and estimated intake of various food categories in 3day food records in 72 patients with type 2 diabetes .\nstatistical calculation was carried out using pasw statistics 18 ( sas institute inc . ) .\nb and denote nonstandardized and standardized regression coefficients , respectively . for analysis of changes of hba1c levels ,\nthe correlation coefficient squared ( r ) was 0.550 and the fvalue with 15 degrees of freedom was 3.499 for a pvalue of 0.003 . \n( a ) correlation between estimated intake of fish and seafood with glycated hemoglobin ( hba1c ) reduction ( national glycohemoglobin standardization program [ ngsp ] , % ) 4 months after initiation of dipeptidyl peptidase4 inhibitors ( hba1c ; n = 72 ) .\n( b ) correlation between estimated intake of eicosapentaenoic acid ( epa ) , docosahexaenoic ( dha ) with hba1c ( n = 72 ) .\n( c ) correlation between serum levels of epa , dha and arachidonic acid ( aa ) with hba1c ( n = 20 ) .\nlinear regression analyses were carried out to calculate the correlation coefficient ( r ) and pvalues .\nwe find that changes of hba1c levels on administration of dpp4 inhibitors are associated with estimated intake of fish and estimated intake of dietary n3 pufa , as well as serum epa and dha levels . despite being a retrospective cohort study with a limited sample size ,\nthese findings are clinically important in two respects : ( i ) the efficacy of dpp4 inhibitors can be predicted by serum epa and dha levels ; and ( ii ) consuming more fish with diet therapy can enhance the efficacy of dpp4 inhibitors .\nfurthermore , the current findings suggest that the differing efficacies of dpp4 inhibitors found among different ethnicities might be partly a result of differences in fish consumption .\nalthough many studies have shown the beneficial effects of dietary n3 pufa from fish , the mechanisms involving dietary n3 pufa in dpp4 inhibitor efficacy have not yet been investigated .\nalthough epa and dha have been shown to prevent excessive adiposity , thereby ameliorating insulin resistance in animal models , the effects of n3 pufa on glycemic control in type 2 diabetes itself are somewhat controversial .\ninterestingly , it has been found that epa and dha enhance glp1 secretion , possibly through free fatty acid receptors , such as gpr120 , in glp1secreting cells and mice .\nit is thus possible that dietary n3 pufa and dpp4 inhibitors synergistically increase biologicallyactive glp1 levels to facilitate maintenance of glycemic control , but it remains to be determined whether epa and dha enhance glp1 secretion in patients with type 2 diabetes . in addition , whether the present findings hold true for dpp4 inhibitors in general is not known , as most of the patients in the current study received sitagliptin or alogliptin , and vildagliptin patients were limited .\nwe find that the reduction of hba1c by dpp4 inhibitors significantly correlates with estimated intake of fish , estimated intake of epa and dha , and serum levels of epa and dha .\nfigure s1 correlation between estimated intakesand serum concentrations of eicosapentaenoic acid ( epa ) anddocosahexaenoic ( dha ; n = 16 ) .\ntable s1 association of glycated hemoglobin(hba1c ) reduction and estimated intake of fish , shellfish and other seafood table s2 association of glycated hemoglobin(hba1c ) reduction and estimated intake ofpolyunsaturated fatty acids click here for additional data file .", "answer": "abstractthis study was initiated to identify clinical and dietary parameters that predict efficacy of dipeptidyl peptidase4 inhibitors . \n a total of 72 untreated japanese patients with type 2 diabetes who received dpp4 inhibitors ( sitagliptin , alogliptin or vildagliptin ) for 4 months were examined for changes of glycated hemoglobin ( hba1c ) and body mass index ( bmi ) , and selfadministered 3day food records , as well as serum levels of eicosapentaenoic acid ( epa ) and docosahexaenoic acid ( dha ) . \n dpp4 inhibitors significantly reduced hba1c ( before initiation of dpp4 inhibitors 7.2 0.7% , 4 months after initiation of dpp4 inhibitors 6.7 0.6% [ paired ttest , p < 0.01 vs before ] ) . \n multiple regression analysis showed that changes of hba1c were significantly correlated with baseline hba1c , as well as estimated intake of fish . \n furthermore , changes of hba1c were significantly correlated with serum levels of epa ( r = 0.624 , p < 0.01 ) and dha ( r = 0.577 , p < 0.01 ) . \n hba1c reduction by dpp4 inhibitors is significantly correlated with estimated intake of fish and serum levels of epa and dha . \n ( j diabetes invest , doi : 10.1111/j.20401124.2012.00214.x , 2012 )", "id": 897} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncolonic necrosis has been described as a rare complication after the administration of kayexalate [ 1 , 2 ] . in this case study , we present a case of calcium polystyrene sulfonate - induced colonic necrosis and perforation to remind clinicians of this rare , but dangerous , toxicity associated with this commonly used medication .\na 78-year - old woman with stage 4 chronic kidney disease ( ckd ) due to chronic pyelonephritis , and a right hypoplastic kidney was presented to our emergency department with a 2-day history of abdominal pain .\nher medical history included epilepsy that was treated with carbamazepine , hypertension and hyperlipidaemia , for which she received carvedilol and atorvastatin . because of the persistent hyperkalaemia\n, she was treated with calcium polystyrene sulfonate at 30 g / day ( anti - potassium granule ; assos drug , istanbul , turkey ) . as a result of the ckd ,\nshe was prescribed calcitriol for a mineral and bone disorder , darbepoetin alpha for anaemia and sodium hydrogen carbonate for acidosis . upon initial physical examination ,\nher abdomen was non - distended with normoactive bowel sounds , but there was diffuse tenderness in her abdomen .\nsignificant laboratory values at the time of admission included sodium 138 meq / l , potassium 4.6 meq / l , ph 7.20 , bicarbonate 13 meq / l , blood urea nitrogen 71 mg / dl , creatinine 2.6 mg / dl , leukocytes 15 500/mm , eosinophils 110/mm , haematocrit 32.7% , platelets 221 000/mm and c - reactive protein 10.9 mg / dl . on the second day of hospitalization ,\nthe abdominal pain worsened and free air under the diaphragm was found on abdominal radiography .\nher sigmoid colon was found to be necrotic and perforated . a biopsy was performed and the perforated segment was repaired by primary closure .\nthe surface of the deep ulcer contained necroinflammatory debris and various sized fragments of basophilic crystalloid material with angulated margins on microscopic examination ( figure 1a and b ) .\nalso , there were no features of chronic colitis , including inflammatory bowel disease or chronic ischaemic colitis .\n( a ) the basophilic crystalloid material in the necroinflammatory background of the ulcer surface ( haematoxylin and eosin , original magnification , 100 ) .\n( b ) the basophilic crystalloid material in the necroinflammatory background of the ulcer surface ( haematoxylin and eosin , original magnification , 400 ) .\nsodium polystyrene sulfonate can also bind intraluminal calcium , leading to constipation , fecal impaction and subsequent bowel obstruction or perforation .\ngerstman et al . reported a 0.27% overall incidence , with a higher incidence ( 1.8% ) during the postoperative period .\nsorbitol enemas , along with experimental evidence suggesting that the necrosis was due to sorbitol rather than the kayexalate in presence of uraemia .\nextensive transmural necrosis was noted in rats receiving enemas of sorbitol or kayexalate in sorbitol in both the uraemic and non - uraemic groups . as in this case report\n, renal failure may be an important facilitating factor in the pathogenesis of the necrosis .\nin contrast to the experimental data , our case was treated with calcium polystyrene sulfonate orally , not rectally .\nrashid et al . noted that kayexalate in sorbitol given as an enema or orally to treat hyperkalaemia has been reported to induce intestinal necrosis in uraemic patients .\nthey studied clinical and pathologic features of 15 patients and observed kayexalate crystals in tissue specimens from surgical resections and endoscopic biopsies .\none possibility is elevated renin levels , commonly seen in renal insufficiency , that predispose the patient to non - occlusive mesenteric ischaemia via angiotensin - mediated vasoconstriction\n. one gram of kayexalate possesses a theoretical in vitro exchange capacity of 23.1 meq of potassium and in vivo capacity of 1 meq .\nemmett et al . reported that in vivo potassium - binding capacity may be lower than previously estimated , more on the order of 0.40.8 meq / g of kayexalate resin .\nin contrast to other minor digestive complications associated with kayexalate treatment , colonic perforation results in significant morbidity and mortality . as a result ,\npotassium exchange resins may , although rarely , induce a colonic perforation , and this diagnosis should be considered in a patient treated as such in case of acute abdomen\n. the clinicians must be aware of the possible rare and serious complications of potassium exchange resins .", "answer": "sodium or calcium polystyrene sulfonate ( kayexalate or analog ) is an ion - exchange resin commonly used to treat hyperkalaemia in patients with chronic kidney disease . \n it is known to cause digestive complications , such as nausea , vomiting and constipation . \n although rare , colonic necrosis and perforation are very severe complications associated with the medication . in this case report , we present a case of calcium polystyrene sulfonate - induced colonic necrosis and perforation to remind clinicians of this rare , but dangerous , toxicity associated with this commonly used medication .", "id": 898} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe prevalence of syphilis in the normal population has decreased significantly since 1977 in korea ( 1 , 2 ) . however ,\nin western countries the incidence of syphilis has risen , mainly in the 20 - 24 age group and its clinical manifestations have been various ( 3 ) .\nsexual activity has become more acceptable in our culture recently , initiating various forms of sex , and as a result , many different clinical conditions of sexually transmitted disease ( std ) have appeared .\nit is usually asymptomatic and less frequently presents as proctitis , ulcer and pseudotumors ( 3 , 4 ) .\ntherefore , it is difficult to diagnose and physicians occasionally might prescribe inappropriate treatments ( 5 , 6 ) . in this paper\nwe describe a case of primary rectal syphilis which was suspected to be rectal cancer .\nhe complained of bowel habit change with tenesmus , mucous discharge , anal pain and intermittent presence of blood in stool .\nhe had a 2 cm sized , firm , non - tender and indurated nodule on the left side of the inguinal area and multiple condyloma acuminatum around the anus .\nsigmoidoscopy in our gastrointestinal endoscopy unit showed two indurated masses of 1.5 to 2 cm on the posterior wall of the middle and lower rectum ( fig .\nthe masses had a coin like appearance , and each of them had a slightly depressed and ulcerated surface .\nthe vdrl quantitative test was 1:64 and the fta - abs igm and igg test was positive . a human immunodeficiency virus ( hiv )\nthe patient was treated with intramuscular penicillin g benzathine ( 2,400,000 iu im/1 week , thrice ) .\nfollow - up sigmoidoscopy after 1 month showed nearly complete regression of the chancre ( fig .\na repeat biopsy was done and the histologic result showed focal lymphoid hyperplasia . a vdrl quantitative test after 3 months was 1:1 .\nmost physicians have a tendency to consider rectal ulceration as a neoplasm ( 7 , 8) . similarly in our case symptoms and signs suggested rectal neoplasia and the clinical history did not reveal homosexuality .\nhowever , after the vdrl test the patient confessed that he had been raped by a homosexual male . therefore , when rectal syphilis is suspected ( i.e. , perianal condyloma acuminatum associated with inguinal lymphadenopathy ) the history of sexual intercourse , especially rectal intercourse , has to be taken .\na dark - field examination is recommended by many studies ( 3 ) . in our case , however , a dark - field examination was not performed , because rectal chancre was highly suggested by the clinical history , anorectal lesions , pathologic findings and positive serologic test . additionally , like other syphilis cases benzathine penicillin therapy induced a rapid regression of the rectal lesions .\nwe believe when a positive serologic syphilis test is associated with ulcerative lesion , additional laboratory tests are not necessary .\ninguinal lymphadenopathy need not require an initial biopsy when evidence of regional infection is present . usually after antibiotic therapy of at least 4 weeks\n, most physicians might decide whether a biopsy is necessary . in this case , however , the physician did not have experience recognizing rectal syphilis , so he immediately obtained a biopsy specimen from the inguinal lesion .\n. in western countries the incidence of rectal syphilis is rising , especially in groups of active homosexual males .\nbassi et al . emphasized in his case report that endoscopists should keep in mind the rising incidence of syphilis ( 3 ) .\ntherefore an initial physician should encourage his / her patient to inform him / her of the patient 's sexual history .", "answer": "a 30-yr - old man was referred for suspicious rectal cancer because of ulcerated lesions in the rectum and a palpable mass in left inguinal area . \n sigmoidoscopy showed two indurated masses and histologic evaluation of biopsy revealed obliterative endarteritis with heavy plasma cell infiltration . both venereal disease research laboratories ( vdrl ) and \n fluorescent treponemal antibody absorption ( fta - abs ) tests were positive . \n after injection of penicillin g benzathine for 3 weeks , the rectal chancre and the palpable mass disappeared .", "id": 899} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nkeloid is a cutaneous fibrous scar that represents disequilibrium in the dermal wound healing process .\npressure therapy is used in the management of keloids , generally in combination with other therapies .\nthis clinical report presents use of pressure through customized appliances for therapy and prophylaxis of the ear keloids in a young female patient .\na 26-year - old female patient was referred from the department of plastic surgery for the fabrication of ear clip for ear keloid .\nthere was history of first ear piercing of lobe of the ears at the age of 10 years without any swelling following piercing .\nadditional ear piercing was done at the age of 24 years at the helix of both ears .\na small swelling appeared on the superior aspect of helix of ears bilaterally after 3 - 4 months of piercing , which gradually increased in size and continued to grow until it reached the present size on the right ear in 1 year duration .\nsurgical excision of keloid on the left ear was done 1 week back . on examination , a small , oval , sessile , non - tender , smooth - surfaced swelling was present on the upper part of helix of the right ear , measuring 8 mm superoinferiorly and 6 mm anteroposteriorly . on the left ear , there was a healed scar on the superior aspect of the helix .\nthere was no pain , pruritus , or other adverse accompanying symptoms except that it caused emotional stress due to impaired esthetics .\nit was planned to use pressure therapy to reduce the size of the growth on right ear and to prevent recurrence on the left ear .\ncustom - made methyl methacrylate pressure appliances were planned to be used for presurgical compression of the keloid on the right ear and passive methyl methacrylate pressure appliance for preventing recurrence on the left ear .\npatient 's skin over the right ear and keloid was lubricated with petroleum jelly and external auditory meatus was blocked .\nimpression compound ( dpi pinnacle ; dpi , india ) was used to make beading around the auricle for the confinement of the impression material [ figure 1 ]\n. then thin mix of irreversible hydrocolloid impression material ( zelgan 2002 ; dentsply , india ) was poured within the confinement of the beading with patient 's head tilted opposite to the side for which impression was being made .\nbell pins were placed in the partially set hydrocolloid for the retention of backing material .\nthin mix of plaster of paris ( kaldent ; kalabhai karson pvt ltd , mumbai , india ) was poured over the irreversible hydrocolloid as the backing material .\nthe impression was poured in dental stone ( kalstone ; kalabhai karson pvt ltd ) with adequate land area to make the cast [ figure 2 ] .\na spring was designed using 21 gauze stainless steel wire that was made as a v - shaped loop with a helix at its apex and adapted over the growth on the cast .\na custom - made pressure appliance was fabricated incorporating this loop in clear methyl methacrylate and characterization was done to make the appliance more esthetically acceptable and unnoticeable to others [ figure 3 ] .\ncare was taken to ensure adequate space for acrylic resin between the wire loop and the skin to avoid direct contact of the stainless steel wire with the skin .\nthe design of the appliance involved covering the whole of the surface of the growth with gap between the two almost equal halves to permit activation in order to ensure sustained pressure , thus allowing adjustments to accommodate the reduced size and negating the need for fabrication of a new appliance .\nimpression compound beading around the right auricle with blocked meatus master cast of right auricle showing keloid on helix custom - made pressure appliance with spring on the right ear helix the master cast for the left ear was obtained following the same procedure as that for lubrication , blocking , and impression of the right ear [ figure 4 ] .\na custom - made passive pressure appliance was planned with incorporation of magnets for retention .\nit was fabricated by adapting methyl methacrylate without any spacer , around the scar over the helix .\ntwo pairs of 2 2 mm magnets ( tt magnets , mumbai , india ) were incorporated in the acrylic resin with two similar poles of magnets in each half [ figures 5 and 6 ] .\nas there was no gap planned between the two halves of the appliance , it did not put any active pressure on the scar that could cause soreness . however\n, it would prevent any growth above the surface by confinement of the soft tissue to the internal dimensions of the appliance .\npost - excisional scar on the left ear helix prophylactic appliance on the scar on the left ear helix two - part prophylactic appliance incorporating magnets the appliances were finished , polished , and adjusted to remove any sore spots . these were delivered and patient was instructed to wear them all the time .\nshe was also instructed about their use , maintenance of hygiene , and regular follow - up .\npatient was counseled about any probable post - surgical nodule and close monitoring for recurrence .\nthe periodic activation of the active pressure appliance was done by closing the coil of the spring .\npatient was monitored for use of the appliances regularly . during follow - up , a 1 mm reduction in overall size of the right keloid was achieved after 3 months and the growth appeared shrunken in appearance [ figure 7 ] .\nno other complication was observed during treatment . reduced and shrunken keloid on the right ear helix healed scar on the left ear helix\npatient 's skin over the right ear and keloid was lubricated with petroleum jelly and external auditory meatus was blocked .\nimpression compound ( dpi pinnacle ; dpi , india ) was used to make beading around the auricle for the confinement of the impression material [ figure 1 ]\n. then thin mix of irreversible hydrocolloid impression material ( zelgan 2002 ; dentsply , india ) was poured within the confinement of the beading with patient 's head tilted opposite to the side for which impression was being made .\nbell pins were placed in the partially set hydrocolloid for the retention of backing material . thin mix of plaster of paris ( kaldent ; kalabhai karson pvt ltd , mumbai , india ) was poured over the irreversible hydrocolloid as the backing material .\nthe impression was poured in dental stone ( kalstone ; kalabhai karson pvt ltd ) with adequate land area to make the cast [ figure 2 ] .\na spring was designed using 21 gauze stainless steel wire that was made as a v - shaped loop with a helix at its apex and adapted over the growth on the cast .\na custom - made pressure appliance was fabricated incorporating this loop in clear methyl methacrylate and characterization was done to make the appliance more esthetically acceptable and unnoticeable to others [ figure 3 ] .\ncare was taken to ensure adequate space for acrylic resin between the wire loop and the skin to avoid direct contact of the stainless steel wire with the skin .\nthe design of the appliance involved covering the whole of the surface of the growth with gap between the two almost equal halves to permit activation in order to ensure sustained pressure , thus allowing adjustments to accommodate the reduced size and negating the need for fabrication of a new appliance .\nimpression compound beading around the right auricle with blocked meatus master cast of right auricle showing keloid on helix custom - made pressure appliance with spring on the right ear helix\nthe master cast for the left ear was obtained following the same procedure as that for lubrication , blocking , and impression of the right ear [ figure 4 ] .\na custom - made passive pressure appliance was planned with incorporation of magnets for retention .\nit was fabricated by adapting methyl methacrylate without any spacer , around the scar over the helix .\ntwo pairs of 2 2 mm magnets ( tt magnets , mumbai , india ) were incorporated in the acrylic resin with two similar poles of magnets in each half [ figures 5 and 6 ] .\nas there was no gap planned between the two halves of the appliance , it did not put any active pressure on the scar that could cause soreness .\nhowever , it would prevent any growth above the surface by confinement of the soft tissue to the internal dimensions of the appliance .\npost - excisional scar on the left ear helix prophylactic appliance on the scar on the left ear helix two - part prophylactic appliance incorporating magnets the appliances were finished , polished , and adjusted to remove any sore spots .\nshe was also instructed about their use , maintenance of hygiene , and regular follow - up .\npatient was counseled about any probable post - surgical nodule and close monitoring for recurrence .\nthe periodic activation of the active pressure appliance was done by closing the coil of the spring .\npatient was monitored for use of the appliances regularly . during follow - up , a 1 mm reduction in overall size of the right keloid was achieved after 3 months and the growth appeared shrunken in appearance [ figure 7 ] .\nno other complication was observed during treatment . reduced and shrunken keloid on the right ear helix healed scar on the left ear helix\nkeloid represents an exuberant reparative process clinically appearing as elevated nodular growth that generally does not regress spontaneously .\npostoperative radiation therapy is a safe and effective therapy in reducing the recurrence of keloids after excision surgery .\nbetter patient compliance has been observed with radiation therapy as compared to postoperative corticosteroid injections .\nthey are effective for prevention and treatment of keloids , especially the newer keloids , but atrophy , telangiectasias , and hypopigmentation have been the common adverse effects .\npressure therapy is used in the management of keloid scars , generally in combination with other forms of therapy .\nthis form of therapy was popularized after the beneficial effects of pressure stockings were observed in healing of burn scars .\npressure appliances such as various springs are used for maintaining pressure after surgical removal and to prevent post - surgical recurrence .\npressure clip is used as in conservative treatment and is an essential adjuvant for early maturation of the scar tissue and prevents the recurrence of keloid . in order to control the pressure and avoid soreness , it is mandatory to fabricate custom - made clip or stent .\nthe appliances described involve simplified design and use of small magnets that makes them highly retentive and stable and do not cause any pressure simultaneously .\nthe materials used for fabrication include acrylic resin , stainless steel wire , and commonly available magnets , making it a low - cost alternative .\nthis article describes a clinical report of a young female patient with ear keloid for which simple and logical therapeutic and prophylactic appliances were fabricated .\nthe described pressure appliance is active for the sustained compression of the keloid and passive for the prophylaxis of recurrence in surgically removed ear keloid .", "answer": "keloid is cutaneous lesion characterized by fibrous growth produced as a result of aberration in the healing process . \n pressure therapy , in combination with other forms of therapy , is used for the management of keloids . \n clips or stents are generally used for the therapy and prophylaxis . \n this report presents use of presurgical compression and prophylactic passive pressure therapy with acrylic appliances for auricular keloids in a patient . \n spring and magnets were used in the design of custom - made appliances for compression and retention .", "id": 900} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntechniques and equipment to accomplish endotracheal ( et ) intubation were the precursor to modern day invasive mechanical ventilation . in recent years , however , the popularity of the et tube has waned .\nclinically , the et tube is seen as an impediment to spontaneous breathing , a transit route for bacteria to the lower airway , and with the advent of noninvasive ventilation a device to be avoided when possible .\nof particular interest has been the effect of the et tube on work of breathing and methods to eliminate this work .\ncommonly , pressure support ventilation ( psv ) has been suggested as the technique of choice for eliminating imposed work due to the et tube .\nmore recently , the technique of automatic tube compensation ( atc ) has become available to specifically address this issue . in this issue of critical care , maeda and\ncolleagues compare the technique of atc , as provided by the drager evita 4 ( dragerwerks , lubeck , germany ) and the puritan bennett 840 ( carlsbad , ca , usa ) , versus psv in reducing imposed work of breathing in a lung model . before i comment on the merits of the study ,\nclearly , before the advent of pressure support ventilation in the early 1980s , patients were successfully weaned using t - piece trials and intermittent mandatory ventilation , with no apparent untoward effects .\nin 1986 , shapiro and coworkers presented data from three normal volunteers breathing through et tubes at a constant tidal volume of 500 ml .\nthat report is widely quoted but is limited by the use of unintubated normal individuals and the requirement for a constant tidal volume during increasing respiratory rates .\nadditionally , close review of the data demonstrates that with a size 8.0 et tube the work of breathing in joules per minute does not become excessive until minute ventilation exceeds 15 l / min .\nbrochard and colleagues compared work of breathing during assisted ventilation , four levels of pressure support , continuous positive airway pressure , and after extubation in an effort to determine the role of pressure support in overcoming the imposed work presented by the et tube . that trial evaluated both patients with normal lungs and those with chronic obstructive pulmonary disease ( copd ) . the authors concluded that the pressure support level that eliminated imposed work was between 3 and 14 cmh2o .\ninterestingly , this was determined retrospectively by matching the work of breathing after extubation to the level of pressure support that resulted in equivalent work of breathing during mechanical ventilation .\nrecent work suggests that the work of breathing postextubation may actually increase compared with work of breathing through the et tube , raising questions about the conclusion of the study by brochard and colleagues .\nweissman evaluated flow - volume loops in 18 postoperative patients intubated with size 7.0 and 8.0 et tubes and found that only ' minimal limitation to airflow ' occurred at volumes and frequencies associated with tidal breathing .\nthat study is one of the very few that contemplate the idea that et tube resistance may not be important when the appropriate size is chosen and the patients pulmonary function has improved to the point that weaning may be considered . of course\n, there are numerous other studies that suggest that et tube resistance may represent a significant impediment to spontaneous breathing .\nhowever , it is important to note that although there remains concern about et tube resistance , and the literature is replete with lung model studies of increased work of breathing , there is not a single clinical trial that suggests that spontaneous breathing through the et tube results in untoward outcomes .\nthe report by maeda and coworkers in this issue of critical care evaluates the two most popular methods of overcoming et tube resistance , namely psv and atc .\nthe authors concluded that tube compensation could not overcome the pressure time product associated with triggering and that pressure support is as effective as atc at 100% .\nthere are , however , tremendous disadvantages to a lung model study in comparing these techniques .\ncalculating the pressure time product and work includes the work required to trigger the ventilator , which can only be overcome by direct measurement of tracheal pressure and triggering from the tracheal signal .\nthis method has been proposed by many , and advanced by the group from gainesville . additionally ,\nalthough the lung model allows consistency , it can not react to differences in gas delivery . in several human studies comparing psv with atc\n, the slow flow and longer inspiratory time associated with psv has been associated with dysynchrony . when used in a patient with copd ,\nthe patient 's high airway resistance and increased compliance allow even small amounts of psv to cause hyperinflation and auto - peep ( positive end - expiratory pressure ) .\nalterations in pulmonary mechanics , along with the preference of the copd patient for short inspiratory times and long expiratory times , result in neuromechanical dysynchrony during psv .\nthe main proposed advantages of atc over psv are reduced work of breathing as patient demand varies , preservation of a normal , variable breathing pattern , and improved synchrony . in a recent trial of spontaneous breathing before extubation , haberthur and coworkers failed to show any advantage of atc over psv or t - tube trials .\none issue not addressed in the study by maeda and coworkers is the role of expiratory compensation .\none distinct difference in the operation of the drager evita 4 and puritan bennett 840 is that evita 4 provides both inspiratory and expiratory compensation for et tube resistance . in these cases\n, the airway pressure may be allowed to drop below peep to facilitate expiratory flow .\nnew modes and new techniques are developed in the hope of resolving clinical problems and often concentrate on a short - term physiologic end - point .\nconventional wisdom suggests that the et tube is an impediment to efficient spontaneous breathing , yet clinical evidence during spontaneous breathing trials appears to argue to the contrary\n. the real question may be whether overcoming et tube resistance is necessary , not whether atc is as good as or better than psv .\nthe future of atc , like many new techniques , may not be in overcoming et tube resistance , but as a method of support during spontaneous breathing that improves patient - ventilator synchrony as compared with psv .\nadditional clinical studies are required to complement the excellent laboratory work by the group from osaka reported in this issue .\natc = automatic tube compensation ; copd = chronic obstructive pulmonary disease ; et = endotracheal ; peep = positive end - expiratory pressure ; psv = pressure support ventilation .", "answer": "concerns about the work of breathing imposed by the endotracheal tube have led clinicians to routinely use pressure support to overcome this resistive component . \n more recently , ventilator manufacturers have introduced systems to automatically overcome endotracheal tube resistance , regardless of tube diameter or patient demand for flow . despite the theoretical advantages \n , neither method appears to provide superior performance . stepping back \n , the real question may be , is overcoming endotracheal tube resistance really important ?", "id": 901} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\noculo - orbital malformations are developmental anomalies of the eye and/or ocular adnexa . in europe , its prevalence in the general population varies between 2.2 and 14 per 10,000 births.1 african studies have mainly reported cataract and congenital glaucoma as the most frequent types of eye malformations.24 malformations of the eye and orbit can be isolated or associated with other systemic malformations . to the best of our knowledge ,\nthe aim of this study was to describe the clinical aspects of a series of oculo - orbital malformations among children seen at the ophthalmology unit of the yaound gynaecology , obstetrics and pediatrics hospital .\nwe carried out a retrospective study in which all children aged 05 years who were seen at the ophthalmology unit of the yaound gynaecology , obstetrics and pediatrics hospital from january 2003 to december 2009 were included .\nthe medical records of all children diagnosed with a malformation of the eye and/or ocular adnexae were retained . in children with multiple malformations ,\nthe following variables were analyzed : age at first consultation ( diagnosis ) , sex , and the various malformations observed .\na total of 2254 children aged 05 years were examined in the ophthalmology unit during this period , and 150 of them were diagnosed with eye malformations , representing 6.65% of our consultations .\nthere were 78 boys ( 52% ) and 72 girls ( 48% ) , corresponding to a male - to - female ratio of 1.08 .\neye malformations were diagnosed in 71.66% ( n = 107 ) of cases during the first year of life .\ntable 1 presents the distribution of children according to the age at which their malformation was diagnosed .\ndiagnosis was made in 72.66% of cases ( n = 109 ) during the first year of life , with 11.33% of cases ( n = 12 ) diagnosed during the first month .\na total of 159 malformations were identified from the 150 files selected , considering that a child could present with one or several malformations . congenital lacrimal duct obstruction ( cldo ) was the most frequent malformation , with a total of 106 cases out of 159 ( 66.66% ) .\nit was unilateral in 90 patients ( 84% ) and bilateral in 16 patients ( 15.10% ) .\ncongenital cataract was second , with 17 cases ( 10.69% ) , unilateral in 41.18% of cases ( n = 7 ) and bilateral in 58.82% of cases\neight cases of congenital glaucoma were diagnosed ( 5.03% ) ; it was more frequent among boys ( five boys against three girls ) .\ncongenital glaucoma was diagnosed in 62.5% ( n = 5 ) of cases before the age of 1 year and in 37.5% of cases ( n = 3 ) between 1 and 3 years . with regards to microphthalmos , eight cases ( 5.03% )\nsix cases of ptosis ( 3.77% ) were recorded and one bilateral aniridia associated with a case of congenital glaucoma without an associated systemic anomaly .\nthe relevance of this study lies in the fact that it is a pioneer study in this domain in cameroon .\nit is intended to provide the basis for prospective studies that will specifically target each of the anomalies identified , especially the most frequent ones .\na prevalence of 1.7% was reported in nigeria by lawan2 and 2.2% in the democratic republic of the congo by kaimbo wa kaimbo et al.5 the difference between these results may be explained by the heterogeneous nature of the study population in each study .\nthe age group was 010 years in the study carried out by lawan ; and 025 years in that by kaimbo wa kaimbo et al .\nthe true prevalence of eye malformations could not be determined in this study because the total population served by this unit could not be easily assessed .\nthe yaound gynaecology , obstetrics and pediatrics hospital is a referral center for the management of mother - and - child diseases , and therefore the majority of children seen are referred cases .\nseveral authors have reported that males are more affected.27 late diagnosis , which was observed in this study , might be due to the lack of attention given to suspicion of eye malformations in infants by mothers and medical practitioners .\non the contrary , studies carried out in europe report a diagnosis rate of 80% during the first week of life.8,9 in this study , congenital cldo was the most frequent malformation .\nthis is contrary to the studies conducted by lawan2 and bodunde and ajibode,3 both in nigeria , where cldo was the third - commonest eye malformation after congenital cataract and congenital glaucoma .\ncldo among children is most often caused by failure of hasner s valve to open spontaneously.10 the majority of cases resolve spontaneously during the first year of life with massage and local antibiotic therapy.11,12 congenital cataract , which was the second most frequent malformation in this study , is the main cause of blindness and low vision among children.13 mature forms require early surgery as well as long - term and rigorous management of amblyopia , which requires the participation of the child and his / her family.14 in immature forms allowing for visual development , surgery may be delayed until the child starts learning to read or even until it becomes impossible for normal schooling.14 intrauterine infections by toxoplasmosis , rubella , cytomegalovirus , and herpes ( torch ) microorganisms , especially congenital rubella , are known for being responsible for congenital cataract.4,15 torch infection screening , although recommended during pregnancy , is not always done for several reasons : firstly , practitioners do not frequently request the tests , and secondly , even when requested , they are not done due to lack of means to pay .\ncameroon is a developing country without a social security policy allowing for low - cost medical coverage .\ncongenital glaucoma ( figure 1 ) was diagnosed in 62.5% of cases during the first year of life .\nthis is less than those reported by several african studies,6,7,16 in which the diagnosis was made in 73%82% of cases during the first year of life .\nit is also lower than the result obtained by zech and ravault in lyon , who reported 80% of cases before the age of 1 month.8 congenital glaucoma presents a surgical emergency , but the delay in diagnosis and hence late management in the african context might be explained by the fact that parents are ignorant about the signs .\nthe equal distribution between bilateral and unilateral forms is contrary to data published in the literature , where bilateral cases are more predominant .\nthis predominance is explained by the hereditary nature of the illness.79 microphthalmos was eight times more frequent than clinical anophthalmos ( figure 2 ) , both of which are incompatible with normal visual development resulting from an arrest in the development of the primary optic vesicles at the embryonic stage.17 with regards to ptosis , its prevalence worldwide is unknown , and it is unilateral in most cases.18 in severe cases of ptosis , the drooping eyelid can cover part of or the entire pupil and interfere with vision , resulting in amblyopia.19 bilateral aniridia is rare , with prevalence varing between 1/64,000 and 1/100,000.20,21 it is caused by a mutation in the pax6 gene , located on human chromosome 11 , and is usually associated with other eye and systemic anomalies .\ncataract is found in 50%85% of patients suffering from bilateral aniridia.20 ectopia lentis , which is considered a major diagnostic criterion for marfan s syndrome,22 was found in one patient .\nit is caused by a deficient development of the zonule , which like elastic tissue is of mesodermic origin.23 goldenhar syndrome ( figure 3 ) also known as oculoauriculovertebral dysplasia , is a rare congenital anomaly involving derivatives of the first and second branchial arches.24 its main ocular manifestation is limbal dermoid , which is found in 30%60% of cases and is a cause of astigmatism , amblyopia , and strabismus.25 persistent hyperplastic primary vitreous results from failure of the primary vitreous and hyaloid vasculature to regress .\nits unilateral localization , which was found in this study , exists equally in literature , where it represents 90% of cases.26 other malformations , such as cryptophthalmos , iris coloboma , and the usher syndrome , described in the literature4,15 were not identified in this study .\neye malformations in children may lead to visual impairment . consequently , systematic postnatal screening for early detection and management are recommended .\nclose collaboration among pediatricians , general practitioners , and ophthalmologists for a multidisciplinary care approach is necessary .", "answer": "summarythe aim of this work was to describe the clinical aspects of eye malformations observed at the ophthalmology unit of the yaound gynaecology , obstetrics and pediatrics hospital.patients and methodswe carried out a retrospective study of all malformations of the eye and its adnexae observed among children aged 05 years who were seen at the ophthalmology unit from january 2003 to december 2009.resultsout of the 2254 children who were examined , 150 ( 6.65% ) presented eye malformations . \n the mean age was 14.40 4 months . \n eye malformations were diagnosed in 71.66% of cases during the first year of life . \n the most frequent malformations were congenital lacrimal duct obstruction ( 66.66% ) , congenital cataract ( 10.9% ) , congenital glaucoma ( 10.9% ) , microphthalmos ( 5.03% ) , and congenital ptosis ( 3.77%).conclusioneye malformations among children can lead to visual impairment and are a cause for discomfort to children and parents . \n therefore , systematic postnatal screening is recommended to enable early management .", "id": 902} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmidaortic syndrome ( mas ) is a rare disease characterized by luminal narrowing of the abdominal aorta , and involves stenosis of the major branches in the abdomen . in 1963\n, the first paper was published describing the narrowing of the descending aorta as mas , unlike takayasu 's syndrome that involves the aortic arch and leriche syndrome that involves aortic bifurcation1 ) .\nclinical manifestations typically include malignant hypertension , claudication , or abdominal angina in adolescents and young adults . in children\n, hypertension is an undervalued problem , which can be fatal or lead to a life - threatening emergency if untreated .\nhypertension with mas is severe and often unresponsive to several antihypertensive drugs , ultimately requiring surgical intervention . here\n, we report a case of a 3-year - old boy presenting with left ventricular hypertrophy , who was diagnosed with idiopathic mas following identification of severely elevated blood pressure ( bp ) .\nan echocardiogram showed mild left ventricle ( lv ) hypertrophy , and he was referred to seoul national university children 's hospital for further management .\ntransthoracic echocardiogram revealed mild lv hypertrophy with increased lv mass index ( 89 g / m or 52 g / m , fig .\neven though he did not complain of any symptoms at the time , we administered carvedilol 3.125 mg every 12 hours for lv reverse remodeling . during a routine follow - up echocardiogram 9 months later , we found abnormally increased celiac artery velocity with a diastolic tail ( peak velocity of greater than 4 m / sec , fig .\nhe was hospitalized for evaluation of renovascular hypertension and bp management at 4 years of age . on admission\nthe patient 's body weight was 21.2 kg ( > 97th percentile ) and height was 110.1 cm ( > 97th percentile ) .\nhis bp was high ( 206/113 mmhg in the right arm and 194/104 mmhg in the right leg ) .\na chest x - ray showed no significant cardiomegaly and a 12-lead electrocardiogram revealed lv hypertrophy ( fig .\nlaboratory findings on admission were as followings : serum blood urea nitrogen , 17.0 mg / dl ; serum creatinine , 0.53 mg / dl ; serum renin activity , 21.0 ng / ml / h ( reference value , < 6.7 ng / ml / hr ) ; and serum aldosterone , 39.4 ng / dl ( reference value , 335 ng / dl ) .\nrenal artery doppler ultrasonography showed an intermittent tardus parvus spectrogram in both renal arteries with a smaller right kidney ( fig .\n3a ) . under the impression of renovascular hypertension , we performed computed tomographic ( ct ) angiography of the abdomen .\nthe ct angiography revealed severe stenosis at the bilateral renal artery , the ostium of the celiac branch , and the ostium of the superior mesenteric artery with diffuse luminal narrowing of the abdominal aorta into the femoral artery ( fig .\nwe prescribed labetalol continuous infusion , titrated up to 3 mg / kg / hr and administered concomitant oral antihypertensive medications ( amlodipine 2.5 mg twice a day and atenolol 5 mg twice a day ) to decrease the bp .\npercutaneous transluminal renal angioplasty ( ptra ) was planned and abdominal aortogram confirmed diffuse luminal narrowing of the abdominal aorta into the femoral artery ( fig .\nptra was attempted with a 320 mm savvy balloon catheter via the right femoral artery ; however , the effect was unsatisfactory because of the resistance to the balloon dilatation .\nhe was discharged with combinations of 3 oral antihypertensive drugs ( amlodipine 2.5 mg twice a day and atenolol 12.5 mg once a day and enalapril 2.5 mg twice a day ) . at the time of discharge ,\nbp was still high and measured as 134/60 mmhg in the right arm . since three years after first admission , he has been followed up at the outpatient clinic without any complications and is taking 3 combinations of antihypertensive drugs ( amlodipine 5 mg twice a day , atenolol 12.5 mg once a day and enalapril 1.25 mg once a day ) .\nwe described a 3-year - old boy presenting with lv hypertrophy who was diagnosed with idiopathic mas following identification of severely elevated bp . to the best of our knowledge ,\nmas is prone to be referred to as hypoplasia or coarctation of the descending aorta , which presents with symptoms such as headache , claudication , and postprandial abdominal pain .\nsevere hypertension has been known to be the most common presentation leading to congestive heart failure , renal failure and severe lower extremities claudication7 ) .\nprevious studies have reported that mas is commonly diagnosed within the first 3 decades89 ) .\nrecently , the intensive school healthy screening system substantially aids the earlier detection in developed countries , although the patient has had no specific symptoms . moreover\n, the widespread use of radiological modalities such as ct or aortography has led to the better recognition of mas .\nthe etiology of mas is not completely understood , and it can be congenital or acquired . congenital mas is a developmental defect that is caused by both incomplete fusion and overfusion of the paired embryonic dorsal aorta1011 ) .\nthe most common location of stenosis is the proximal renal artery ( up to 80% ) , and at least 25% of cases may occur in the superior mesenteric artery91112 ) .\nacquired mas is caused by takayasu 's arteritis , neurofibromatosis , fibromuscular dysplasia , retroperitoneal fibrosis , mucopolysaccharidosis , and williams syndrome13 ) .\nsevere complications such as congestive heart failure , cerebrovascular disease , and hypertensive encephalopathy present frequently and may be fatal .\nthe response to antihypertensive drugs is known to be poor in hypertension with mas and several previous studies have shown vascular surgery to be the best curative therapy14 ) . as experience with ptra grows ,\nhowever , the ptra success rate decreased with mas compared with isolated renal artery stenosis because of the extensive stenotic nature of the aorta and renal branches15 ) , even though ptra is successful in reducing hypertension by using different technical approaches in the arteries from one study3 ) . in conclusion , we report a 3-year - old boy presenting with left ventricular hypertrophy who was diagnosed with congenital mas following the identification of severely elevated bp . clinical suspicion and accurate examination , including bp measurement , would aid early diagnosis of mas and optimal treatment , and are important to prevent the fatal complications from hypertension .", "answer": "midaortic syndrome ( mas ) is a rare vascular disease that commonly causes renovascular hypertension . \n the lumen of the abdominal aorta narrows and the ostia of the branches show stenosis . \n mas is associated with diminished pulses in the lower extremities compared with the upper extremities , severe hypertension with higher blood pressure in the upper rather than lower extremities , and an abdominal bruit . \n the clinical symptoms are variable , and recognition in children with hypertension can aid early diagnosis and optimal treatment . \n hypertension with mas is malignant and often refractory to several antihypertensive drugs . \n recently , radiologic modalities have been developed and have led to numerous interventional procedures . \n we describe the case of a 3-year - old boy presenting with left ventricular hypertrophy whose severely elevated blood pressure led to the diagnosis of idiopathic mas . \n this case highlights the importance of measuring blood pressure and conducting a detailed physical examination to diagnose mas . \n this is the first reported case of idiopathic mas diagnosed in childhood in korea .", "id": 903} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbecause double stranded ( ds ) dna cleavage is much harder to repair than single stranded ( ss ) dna cleavage , ds damage is particularly efficient in inducing self - programmed cell death or apoptosis .\nthese compounds , often hailed as the most potent family of anticancer agents , produce cleavage of both strands of dna duplex via two hydrogen abstractions from two opposite strands of dna backbone by a reactive biradical , p - benzyne , generated from the enediyne core via a process , called the bergman cyclization [ 46 ] .\nhowever , natural enediynes not only lack selectivity towards cancer cells , but also do not cause the ds cleavage with 100% efficiency .\nthus , design of compounds which are capable of more efficient ds dna cleavage and combine this efficiency with selectivity towards cancer cells remains the focal point of the anticancer therapeutic agents targeting dna . \nwe have found that dna damaging potential of enediynes can be increased if their reactivity is tuned towards c1c5 photocyclizations , a new reaction discovered in our lab which leads to incorporation of four rather than two hydrogen atoms from the environment [ 8 , 9 ] . because c1c5 cyclization proceeds under photochemical conditions for thermal c1c5 cyclization , see [ 10 , 11 ] , it takes advantage of the high degree of spatial and temporal controls over reactivity inherent to the photochemical activation .\nthe use of tissue - penetrating light allows for efficient , and selective , spatial and temporal control over prodrug activation as light can be delivered directly to the tumor when it contains a high concentration of the prodrug .\nskin cancer is the most obvious target for this therapy and , in 2006 , the uk national institute of health and clinical excellence ( nice ) recommended pdt for basal cell carcinoma .\nhowever , pdt can be also used to treat tumors on the lining of internal organs or cavities .\nother tumors can be targeted with low - energy tissue penetrating photons , especially if the three - dimensional control of activation is provided by the two - photon excitation mode . for two photon excitation of enediynes , see [ 1214 ] .\nin addition , this radical - anionic c1c5 cyclization of enediynes is triggered by photoinduced electron transfer ( pet ) .\nthis mechanistic feature increases cellular selectivity because activation is possible only in the direct vicinity of a suitable electron donor such as dna to occur . in the absence of such a donor , tfp - substituted enediynes ( scheme 1 )\nwe have also found that related tfp - substituted monoacetylenes are capable of photochemical alkylation of electron rich -systems [ 1517 ] and investigated whether this reaction can be also used for controlled dna - modification . a priori , efficient dna - cleavage by monoalkynes incapable of the bergman or c1c5 cyclizations can involve several possible mechanisms like base alkylation , hydrogen abstraction , generation of reactive oxygen species as well as pet . \nin order to increase solubility of tfp - warheads in water and their affinity to dna , we combined them with lysine via carboxyl moiety of the amino acid , figure 1 . \nimportantly , this mode of attachment leaves both amino groups of lysine available for an acid - base reaction which converts them into cationic ammonium groups .\nwe found that dna - damaging ability of such hybrid molecules can be fine - tuned in the narrow range of physiological ph conditions which results in a dramatic increase in reactivity at the lower ph of hypoxic tumor cells .\nless basic -amino group is protonated at the lower ph than 7 and this protonation not only prevents quenching the excited state of the chromophore but also provides tighter binding to negatively charged dna .\nremarkably , the change in reactivity occurs at a relatively narrow and predefined ph point ( ~ph 6 ) . \nthese dna - photocleavers provide the dna cleavage ratios of up to the 1 : 2 ds : ss at ph 5.5 at concentrations and irradiation times where almost no ds cleavage is observed at the ph of healthy cells .\nthis dramatic increase of ds dna cleavage at the lower ph renders these molecules more efficient ds dna cleavers than calicheamicine under the conditions suitable for selective targeting of acidic cancer tissues ( figure 2(a ) ) .\nwe also found that the c - lysine conjugates bind selectively to nicks and gaps in a dna duplex and , upon photochemical activation , transform the easily repairable ss - dna damage into much more therapeutically important ds - dna damage ( figure 2(b ) ) .\nthe medicinal potential of these molecules has been illustrated by a > 90% lncap cancer cell death induced by photochemically activated tfp - acetylene - lysine conjugate 3 in one treatment at concentrations as low as 10 nm .\nsimilar increases in reactivity upon activation with light were observed in parallel experiments with umrc3 , umrc6 , and 786-o cancer cell lines . in summary ,\nour previous work led to the development of a family of powerful and tunable dna cleaving reagents which have been shown to cleave both plasmid dna and dna oligomers outside of cells [ 15 , 18 ] .\nwe have also proven that these reagents can induce cancer cells death at the low concentrations . however , our previous work offered no evidence for dna - damage by tfp - enediynes and acetylenes inside of cells .\nsuch evidence is important because cell death can result from mechanisms other than dna cleavage and because dna - cleavage of intracellular dna should be more difficult since this dna is compactly organized around histone proteins .\nthe aim of this work is to test the efficiency of our light - activated ds - dna - cleavers towards intracellular dna using single cell gel electrophoresis assay which can measure dna damage in individual eukaryote cells [ 2125 ] .\nthis assay has been used as a standard technique for evaluation of dna damage / repair , biomonitoring , and genotoxicity testing [ 2633 ] .\nthe cleaved dna fragments are able to migrate out of the cell under an electric field after lysis and alkali treatments while undamaged dna moves slower and remains with the confines of the nucleoid .\nreagent kit for single cell gel electrophoresis assay kit , cometassay , and control cells containing different levels of dna damage , cometassay control cell , were purchased from trevigen , inc .\nthe cc0 sample corresponds to cells with undamaged dna whereas cc1 , cc2 , and cc3 have different levels of dna - cleavage induced with etoposide .\nolympus bx61 microscope attached with the dp71 color digital camera was used to take fluorescence images of scge assay .\ntail moment , the ratio of tail length to head diameter ( l / h ) , dna percentage in tail , and tail length were used to estimate dna damage .\nthe tail moment has been regarded as an appropriate index of induced dna damage by computerized image analysis .\nit represents both the amount of damaged dna and the distance of migration by a single number .\nthe tail moment was calculated by multiplying the percentage of dna in the tail by the tail length ; see .\nlncap cells ( p.35 ) were plated in 6 ( 100 mm ) plates at density of 250,000 cells / well and were maintained in rpmi 1640 medium supplemented with 10% fbs , sodium bicarbonate ( 2 \ng / l ) . when they reach 70% confluence , compound 3 was dissolved in serum - free rpmi 1640 medium supplemented with sodium bicarbonate ( 2 \ng / l ) . after the rpmi 1640 , medium containing the compound 3 ( 0 , 10 , and 50 m ) were added to the cells and the cells were placed in the incubator for 4 hours .\nthe cells were exposed to uv with cover removed for maximum exposure for 10 minutes and were trypsinized and counted .\nsolutions in ice cold 1 pbs ( ca and mg free ) , with 1 10 cells / ml , were prepared based on cometassay instruction from trevigen , inc .\nlmagarose was melt in boiling water bath for 5 minutes and placed in 37c water bath for at least 20 minutes to cool .\ncells at 1 10/ml were combined with molten lmagarose at a ratio of 1 : 10 ( v / v ) and 50 l of the mixture was transferred on cometslides .\nthe slides were placed at 4c in the dark for 30 minutes and they were immersed in prechilled lysis solution . after 30-minute immersion at 4c , the slides were immersed in alkaline solution prepared freshly with naoh ( 0.6 g ) , 200 mm edta ( 250 l ) , and dh2o ( 49.75 ml ) for 20 minutes at room temperature , in the dark .\nthen , the slides were removed from alkaline solution and washed by immersing in 1 tbe buffer for 5 minutes twice .\nafter adding 1 tbe buffer not to exceed 0.5 cm above slides in electrophoresis tank , the voltage at 1 volt per cm was applied for 10 minutes .\nthe slides were immersed in dh2o twice for 10 minutes , then in 70% ethanol for 5 minutes .\nthe samples were dried at 45c for 15 minutes and 100 l of diluted sybr green i was placed on the gels and the slides were stored at refrigerator .\nafter 5 minutes , excess sybr solution was removed by gentle tapping and the slides were completely dried at room temperature in the dark .\nthe control scge assay results for undamaged cells ( cc0 ) and commercially obtained cells with variable amount of dna damage ( cc13 ) are summarized in the top part of figure 3 ( entries ( a)(d ) ) .\nas expected , while scge assay with healthy cells showed no tails indicative of dna damage , the assays with the damaged cells produced characteristic tails , the size of which correlates with the extent of dna damage in these cells .\nwith the pretreated control cells ( table 1 , ( b)(d ) ) , 33 , 47 , and 98% of dna were detected in tails , respectively . \ntail moment values are also consistent with different levels of dna damage . after confirming that assay conditions work in the control cells , we proceed to investigate dna damage induced by conjugate 3 in lncap cancer cells . to find whether uv itself or thermal reactions of compound 3 may be responsible for the dna cleavage in cancer , we included two control experiments with cells exposed to uv for 10 minutes in the absence of a dna - cleaver ( figure 3(f ) ) and with cells treated with 50 m of compound 3 for 4 hours without photochemical activation ( figure 3(g ) ) .\nthis result confirms that neither uv nor compound 3 in the dark can damage dna under these experimental conditions .\nin contrast , photochemical activation of 50 m of compound 3 produced very efficient dna damage ( more than 90% dna in the tail , table 1 ) in individual cells ( figure 3(h ) ) .\nirradiation in the presence of 10 m of compound 3 also showed significant dna damage ( ~40% dna in the tail , figure 3(i ) ) .\nthese results confirm that compound 3 can penetrate into the nucleus of the cancer cell and damage highly compacted dna photochemically . \nthe concentrations of lysine conjugates used in our comet experiments are significantly higher than > 0.01 mm concentrations sufficient to cause significant photocytotoxicity to several cancer cells lines .\nthis difference is not limited to the comet assay our earlier experiments with pure dna also required micromolar concentrations of the conjugate to observe the cleavage [ 18 , 19 ] .\nfirst , it suggests ( somewhat surprisingly ) that the efficiency of cleavage for isolated plasmid dna and compacted cellular dna is not drastically different , thus indicating that our compounds should accumulate in the cell nucleus rather efficiently . \nsecond , this observation may indicate the presence of an additional , even more efficient , mechanism for cytotoxicity which may not be based on dna cleavage .\nalternatively , it may also mean that even small amount of dna cleavage ( which is not detected by the conventional , relatively insensitive assays ) is still sufficient for causing apoptosis .\nalthough we can not distinguish between these two mechanisms at this point , this mechanistic ambiguity renders important the observation that lysine - acetylene conjugate can indeed target and damage cellular dna . \ninterestingly , the fluorescence images of cells treated with compound 3 ( figures 3(g ) and 3(i ) ) showed blue fluorescence in the nucleus region on top of the green fluorescence from the dna - staining dye , sybr green i. because this blue fluorescence is not observed in control cells without the conjugate , the emission is likely to result either from compound 3 itself which has the maximum emission at 440 nm ( figure 4 ) or from one of the respective photoproducts derived from the dna - photocleaver .\nthis observation provides additional evidence that conjugate 3 can be uptaken into the nucleus of cancer cells .\nit is also interesting that there is no residual blue fluorescence in figure 3(h ) , where the dna is broken completely .\nscge assays confirm the occurrence of efficient cleavage of highly compacted intracellular dna by a light - activated c - lysine acetylene conjugate .\nthis result provides a key mechanistic link between efficient dna cleavage and significant cytotoxicity in cell proliferation assays .", "answer": "previously , we reported the design and properties of alkyne c - lysine conjugates , a powerful and tunable family of dna cleaving reagents . \n we also reported that , upon photoactivation , these molecules are capable of inducing cancer cells death . to prove that the cell death stems from dna cleavage by the conjugates \n , we investigated intracellular dna damage induced by these molecules in lncap cancer cells using single cell gel electrophoresis ( scge ) assays . \n the observation of highly efficient dna damage confirmed that lysine acetylene conjugate is capable of cleaving the densely compacted intracellular dna . \n this result provides a key mechanistic link between efficient dna cleavage and cytotoxicity towards cancer cells for this family of light - activated anticancer agents .", "id": 904} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nUsing transcriptome sequencing to identify mechanisms of drug action and resistance\n\nPaper sections:\n\nCurrently, approaches to analyze how a drug works fall into two broad categories. First, several strategies rely on model organisms that are compatible with genetic manipulations1-3. However, many drugs are inactive in these organisms, possibly due to multi-drug resistance mechanisms and target divergence4. Second, affinity-based methods are used to identify proteins that bind the drug5, 6. These approaches are effective when the drug is potent and the targets are reasonably abundant in vivo. However, establishing that a drug-binding protein is the physiological target typically depends on correlations between binding/activity assays in vitro and protein knockdown phenotypes. These correlations can be misleading due to differences between chemical inhibition, which can be acute, and the protein knockdown phenotypes, which can be indirect or from cumulative effects7. Currently, we lack an approach that addresses these limitations and can determine mechanisms of drug action in human cells.
The 'gold standard' in identifying a drug's target is achieved when two criteria are met. First, resistance to a drug in a physiological context occurs through mutation in the target protein. Second, this mutation should suppress inhibition of the target's activity by the drug. This standard is met for a few drugs (e.g. Gleevec), for which focused analyses of the expected target led to such mutations8, 9. However, the human genome's large size and complexity has limited unbiased analyses of mutations conferring drug resistance.
We sought to develop an approach that could achieve 'gold standard' validation of a drug's target and be applied to relevant human cell types (e.g. cancer cells). We reasoned that deep sequencing and bioinformatics could be used to screen the genome of drug resistant clones isolated from cultured human cells for resistance mutations. Moreover, we hypothesized that analyzing mutations common to multiple clones would focus our analysis on a handful of potential drug targets. When combined with biochemical analyses, these data could lead to 'gold standard' validation of the drug's physiological target. As a proof-of-concept we analyzed the mechanisms that confer resistance to drugs whose targets are known.
BI 2536 (Fig. 1a) is currently in clinical trials and inhibits Polo-like kinase 1 (PLK1), a major cell cycle regulator10. To isolate resistant clones we used a human colon cancer cell line, HCT-116, which is deficient in mismatch repair and has low expression of multi-drug resistant (MDR) pumps11. Therefore, HCT-116 behaves like a mutagenized cell line, facilitating the rapid identification of mutations that confer drug resistance12, 13. From fifteen BI 2536-resistant clones (isolated from selections with 10 nM BI 2536, LD50: 3.9 \u00b1 2.8 nM), we selected six for transcriptome sequencing (also called RNA-seq). The LD50s for BI 2536 were 3-9 fold higher in these clones than in the parental cell line (Fig. 1b, Supplementary Results, Supplementary Table 1). In parallel, the parental cell line was also processed for transcriptome sequencing.
The sequencing data were analyzed to identify single nucleotide variations and short insertions/deletions (indels) in each clone, and only those present in coding sequences were further considered. We found 6-14 single nucleotide variations that were significantly increased (with a 0.5% false discovery rate) in the BI 2536-resistant clones, compared to the parental cell population (Supplementary Tables 2-7; no indels were found). Groups of similar clones were identified by analyzing single nucleotide variations using a clustering approach (see Supplementary Methods). Among the six clones, A, B, and C were independent (groups 1, 2, and 3, respectively), while D, E, and F formed a single group (group 4, Fig. 1c). We further focused our analysis on genes that were mutated in more than one BI 2536-resistant group. While there were no genes common to all groups, PLK1 was the only gene mutated in more than one group (Supplementary Table 8).
Two distinct PLK1 mutations were identified, G63S and R136G, both of which map to the binding site of BI 2536 in the crystal structure of PLK1 (Supplementary Fig. 1)14. To examine whether these mutations are sufficient for conferring resistance to BI 2536, we generated stable cell lines expressing wildtype PLK1 and each mutation as a GFP-tagged full-length PLK1 construct. Independent cell lines were used as secondary mutations were less likely to be common between these lines and HCT-116. The R136G mutation suppressed BI 2536 toxicity in hTERT-RPE1 (Fig. 1d), and the G63S mutation suppressed toxicity in hTERT-RPE1 (Fig. 1d) and in HeLa cells (Supplementary Fig. 2). These data suggest that PLK1 is the major physiological target of BI 2536. Published data show that the R136G mutation has reduced sensitivity to BI 2536 in vitro15. Therefore, these data provide the 'gold standard' proof that PLK1 is the target of BI 2536.
BI 2536-resistant group 4 (representing clones D, E, and F) did not have a mutation in the PLK1 gene, suggesting a different resistance mechanism. An unbiased survey of all transcript levels (Supplementary Data 1 and 2), which can be determined from the transcriptome sequencing data, revealed that ABCB1 (P-gp, a drug efflux transporter) was among the most highly over-expressed mRNAs in group 4 clones (Supplementary Fig. 3). Consistent with the hypothesis that the intracellular concentration of BI 2536 was lowered by increased drug efflux, group 4 clones also had reduced sensitivity to the chemically-unrelated drug taxol, a compound known to be transported by the ABCB1 pump16 (Fig. 1e). While further experiments are needed to confirm this resistance mechanism, our data suggest that our approach can lead to testable hypotheses for indirect mechanisms of drug resistance.
We next examined if our approach could be applied to another drug. Bortezomib (Fig. 2a) inhibits the proteasome by targeting its subunit PSMB5 and is used clinically to treat multiple myeloma and mantle cell lymphoma17. Nineteen clones were isolated from HCT-116 cells grown in the presence of bortezomib (8 -12 nM, LD50: 6.3 \u00b1 0.9 nM). Five clones, with reduced bortezomib sensitivity (LD50s 2.4 \u2013 6.5 fold higher, Fig. 2b and Supplementary Table 9), were processed for transcriptome sequencing. 15-28 single nucleotide variations in each clone were identified (Supplementary Tables 10-14). Clustering analysis (Fig. 2c) grouped clones A, B, C, and D together (group 1) while clone E was independent (group 2). Five genes were mutated in both bortezomib-resistant groups, and the only gene with two distinct mutations (M104V and A108T) was PSMB5, the known target of bortezomib (Supplementary Table 15). If the drug target was unknown, all five genes would have to be examined as potential targets. However, the existence of two distinct resistance mutations would make PSMB5 the highest priority for further analysis.
We found that expression of GFP-tagged PSMB5, carrying either of these mutations, suppressed bortezomib sensitivity in an independent cell line (hTERT-RPE1, Fig. 2d). This is consistent with previous reports that A108T confers bortezomib-resistance18, 19. As both mutations in PSMB5 map to the drug's binding site, we hypothesize that they directly suppress drug interactions (Supplementary Fig. 4)20. While additional biochemical tests are needed to examine this further, our data indicate that our strategy can efficiently lead to resistance mechanisms that include a drug's direct target.
Our analysis thus far indicates that for our approach to be effective, resistance via mutations in a drug's direct target must occur at high frequency in drug-resistant clones. To examine this, we sequenced the PLK1 gene in each of the nine BI 2536-resistant clones that we had not processed by RNA-seq. PLK1 was mutated in ~45% of these clones (4 of 9, Supplementary Table 16). We next analyzed two kinesin-5 inhibitors, S-Trityl-L-cysteine (STLC), which is known to be selective21, and 4-(2-(1-phenylcyclopropyl)thiazol-4-yl)pyridine (PCTP), which has been shown to inhibit other related motor proteins in vitro21, 22. Kinesin-5 mutations were found in ~30% of the STLC-resistant clones (4 of 14, Supplementary Fig. 5) and in ~15% of PCTP resistant clones (3 of 22, Supplementary Fig. 6). These data indicate that resistance in a drug's direct target occurs at high frequency when a drug has one major physiological target (as is the case for STLC, BI 2536 and bortezomib). When a drug has multiple targets (e.g. PCTP) it is likely that resistance in a single target will be less frequent and our approach may be limited as a greater number of clones would have to be sequenced to identify mutations common in more than one clone.
In summary, we have developed a method to identify the target of drugs in human cells by examining resistance mechanisms. Our strategy (Fig. 2e) involves isolating multiple drug resistant clones from genetically heterogeneous human cells. Clones with multi-drug resistance can be excluded by testing for reduced sensitivity to unrelated compounds (i.e. taxol). The remaining clones are processed for transcriptome sequencing, along with the parental (untreated) cell population. Bioinformatics is used to find genes mutated in more than one independent clone. These genes are prioritized for further biochemical and cell biological analyses to identify the drug's direct target and indirect resistance mechanisms.
Our strategy has advantages over other approaches to identify a drug's target. First, unlike many other target identification approaches, our method does not rely on chemical modifications of the drug of interest. This can be important when small changes in a drug's chemical composition can alter its mechanism of action23. Second, our approach can enable cell-type specific analyses, which would be particularly useful if a drug is toxic in specific tissues. While our approach is currently limited to analyzing cytotoxic drugs, it should be possible to extend its use to non-toxic drugs by using phenotypic or reporter-based read-outs to select clones with reduced drug sensitivity (e.g. change in fluorescence). Furthermore, as our approach focuses on discovering single nucleotide variations and insertions/deletions, it does not report on all potential mechanisms of resistance. This limitation can be addressed by combining our strategy with other genomic methods, such as exome capture, full genome sequencing, and bisulfate conversion followed by sequencing (to detect DNA methylation). Our approach has the potential to reveal the physiological on-targets of a drug in disease cells, unintended off-targets in healthy cells, and can reveal cellular mechanisms of drug resistance. These findings can impact chemical modifications of drugs to improve efficacy and limit toxicity. When unanticipated drug targets are found new uses of the drugs may also be suggested.
", "answer": "Determining mechanisms of drug action in human cells remains a major challenge. Here we describe an approach in which multiple drug resistant clones are isolated and transcriptome sequencing is used to find mutations in each clone. Further analysis of mutations common to more than one clone can identify a drug\\xe2\\x80\\x99s physiological target and indirect resistance mechanisms, as indicated by our proof-of-concept studies of cytotoxic anti-cancer drugs, BI 2536 and bortezomib.", "id": 905} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsuicide is a grave public health issue with a global mortality rate of 16 per 100,000 individuals.1 suicide is one of the top three leading causes of death , particularly among individuals aged 1544 years , which is a productive age group.1 suicide is a complex event that is influenced by biological , cultural , psychological , and socioeconomic factors .\nmore than 90% of suicide victims were diagnosed with psychiatric problems at the time of death , and approximately two thirds had been diagnosed with depression.2,3 depressed patients tend to consult physicians other than psychiatrists , and a variety of medical professionals , including general practitioners , the staff of emergency departments , and non - psychiatric nurses , are key interveners for preventing suicide . among medical staff members , negative attitudes toward suicide such as\nanger could affect nontherapeutic reactions to suicidal individuals.4 furthermore , a belief that suicide is a personal right was negatively related to suicide intervention skills.5 an accurate assessment of the attitudes toward suicide held by medical staff members is relevant .\nprevious studies have shown that difficulties with parental bonding during childhood could be a predisposing factor for the onset of many psychiatric conditions , such as anxiety , depressive states , and maladjusted behaviors.68 parental bonding and premorbid personality traits play an important role in shaping the developmental trajectory of an individual , including his / her ability to adjust to stressful events .\nalthough few studies have assessed the relationship between parental bonding and mental conditions among medical staff members,9,10 no study has evaluated the association between parental bonding and attitudes toward suicide .\nthe objective of this study was to investigate whether parental bonding is associated with attitudes toward suicide among medical college students in japan .\nstudents in their fifth year of medical school at hirosaki university , hirosaki , japan , participated in the study .\nthe surveys were distributed to 226 medical students . of the distributed 226 surveys , 160 questionnaires ( 116 males and 44 females )\nthe demographic data ( age and sex ) were obtained from self - questionnaires and interviews .\nthe data collection for this study was approved by the ethics committee of the hirosaki university school of medicine , and the subjects provided written informed consent before participating in the project . the parental bonding instrument ( pbi )\nwas administered to each participant to measure the attitudes and behavior of the parents.11 the pbi is a 25 item self - rating instrument by which individuals over the age of 16 report their experiences of being parented to the age of 16 .\na total of 12 items measure the dimension of care , and 13 items measure protection , both on a likert scale .\nthe care dimension of the pbi reflects parental warmth and involvement in contrast to rejection and indifference .\nthe overprotection dimension of the pbi reflects parental overprotection and control in contrast to the encouragement of autonomy .\nhigher scores on the care and protection dimensions reveal that participants perceive their parents to be more caring and/or protective .\nwe employed the japanese version of the attitudes toward suicide questionnaire ( atts ) to assess the attitudes toward suicide held by the study participants.12 we employed a six factor model that was previously developed in studies of japanese attitudes , including \n common occurrence , suicidal expression as mere threat , unjustified behavior , \nimpulsiveness.12,13 each item , with the exception of items 10 and 28 , was scored on a five point scale from 1 ( strongly agree ) to 5 ( strongly disagree ) .\nitems 10 and 28 were scored using a different scoring method that employed a five point scale from 1 ( strongly disagree ) to 5 ( strongly agree ) .\nmultivariate regression analysis was applied to assess the relationship between parental bonding and attitudes toward suicide .\nthe data were analyzed using the pasw statistics software program for windows , version 18.0 .\nstudents in their fifth year of medical school at hirosaki university , hirosaki , japan , participated in the study .\nthe surveys were distributed to 226 medical students . of the distributed 226 surveys , 160 questionnaires ( 116 males and 44 females )\nthe demographic data ( age and sex ) were obtained from self - questionnaires and interviews .\nthe data collection for this study was approved by the ethics committee of the hirosaki university school of medicine , and the subjects provided written informed consent before participating in the project .\nthe parental bonding instrument ( pbi ) was administered to each participant to measure the attitudes and behavior of the parents.11 the pbi is a 25 item self - rating instrument by which individuals over the age of 16 report their experiences of being parented to the age of 16 .\na total of 12 items measure the dimension of care , and 13 items measure protection , both on a likert scale .\nthe care dimension of the pbi reflects parental warmth and involvement in contrast to rejection and indifference .\nthe overprotection dimension of the pbi reflects parental overprotection and control in contrast to the encouragement of autonomy .\nhigher scores on the care and protection dimensions reveal that participants perceive their parents to be more caring and/or protective .\nwe employed the japanese version of the attitudes toward suicide questionnaire ( atts ) to assess the attitudes toward suicide held by the study participants.12 we employed a six factor model that was previously developed in studies of japanese attitudes , including \n common occurrence , suicidal expression as mere threat , unjustified behavior , \nimpulsiveness.12,13 each item , with the exception of items 10 and 28 , was scored on a five point scale from 1 ( strongly agree ) to 5 ( strongly disagree ) .\nitems 10 and 28 were scored using a different scoring method that employed a five point scale from 1 ( strongly disagree ) to 5 ( strongly agree ) .\nmultivariate regression analysis was applied to assess the relationship between parental bonding and attitudes toward suicide .\nthe data were analyzed using the pasw statistics software program for windows , version 18.0 .\ntable 1 presents the items included in the six factor atts with their descriptive data .\npaternal care was significantly associated with paternal protection , maternal care , maternal protection , and right to suicide .\nmaternal care was significantly associated with maternal protection , right to suicide , and common occurrence .\nright to suicide was significantly associated with common occurrence , unjustified behavior , and preventability / readiness to help .\ntable 3 shows the multiple regression analysis of the atts sub - scales with the pbi scores . after adjusting for age and sex ,\nmaternal care approached a statistically significant association with the right to suicide . under the same conditions , maternal care\nthe present study assessed attitudes toward suicide and their associations with parental bonding among japanese medical college students .\nthe majority of the participants in our study agreed that anyone could commit suicide ( 88.8% ) and that suicide is preventable ( 86.3% ) .\nin addition , the multiple regression analysis revealed that participants who reported a higher level of maternal care thought that suicide was a common occurrence and tended to think that people do not have the right to commit suicide .\ndomino and takahashi used the suicide opinion questionnaire to investigate the differences in attitudes toward suicide between students in japan and those in the united states , and the results demonstrated that the scores for right to die and normality were higher in japanese students and that those for aggression were higher in american students.14 etzersdorfer et al compared the attitudes towards suicide held by medical students in madras with those in vienna , finding that medical students in madras rejected the right to commit suicide and assisted suicide to a greater degree than the students in vienna.15 in a swedish study to assess whether attitudes differ between students at the beginning and end of their studies , students in the final year of medical school more frequently considered suicide to be an expression of psychiatric disease and thought that people attempting to commit suicide were not responsible for their actions.16 in addition , a study from japan revealed that sympathetic comments increased with the amount of years in school among students while critical comments decreased.17 in japan , mentality on suicide might be more culturally visible and acceptable than other countries . in past years , suicide was regarded as an honorable solution to personal guilt and failure . regarding occupational differences in attitudes toward suicide ,\nonc et al found that medical students and general practitioners held the most permissive attitudes in turkey.18 in addition , they showed that the attitude scores of general practitioners regarding their preparedness to prevent suicide were lower compared to those of other groups . in japan , kodaka et al reported attitudes toward suicide among pharmacists using the atts.13 more than half of pharmacists reported that people understand the wishes of others to commit suicide , and 16.8% of the participants thought that people who mention suicide do not actually take their own lives .\na 10 year follow - up study of norwegian physicians ( n=631 ) revealed that a low level of maternal care predicted severe depressive symptoms and partially mediated low self - esteem.9 lung et al assessed the psychological effects on 127 health care workers who had cared for suspected severe acute respiratory syndrome ( sars ) patients .\nearly maternal attachment and neuroticism were found to heavily affect mental health during life - threatening stress.10 distinct patterns of parental bonding may contribute to the development of different dysfunctional schemas which may influence attitudes toward suicide.19 there are several limitations in this study .\nfirst , we used pbi to assess the child rearing behavior experienced by our participants .\nalthough pbi has shown basic reliability for long periods,20 we could not completely rule out possible influences of the current mood state or recall bias in individuals because pbi is an instrument for measuring recalled parental behaviors .\nsecond , certain parameters were not assessed in this study personality traits , a history of psychiatric disorders , suicidal behavior , and current mood state could affect the attitude towards suicidal behavior . third , because the participants in our study are medical students , we can not generalize these results to general practitioners .\nour study indicated that the majority of participants seriously believe that anyone could commit suicide .\nparticipants who have experienced a higher level of maternal care thought that suicide occurs commonly and tended to think that people do not have the right to commit suicide .\nalthough parental bonding predisposes these attitudes toward suicide , educational programs could change caretaking practices.21 to achieve more positive attitudes towards suicidal behavior , promoting the best practices for suicide prevention is needed for medical students .", "answer": "backgroundsuicide is a grave public health issue that is responsible for a high mortality rate among individuals aged 1544 years . \n attitudes toward suicide among medical staff members have been associated with appropriate therapeutic responses to suicidal individuals . \n the aim of this study was to examine the effects of parental rearing on attitudes toward suicide among japanese medical college students.methodswe examined the association between parental bonding and attitudes toward suicide in 160 medical college students in japan . \n the parental bonding instrument was used to assess the attitudes and behaviors of parents . \n the attitudes toward suicide were evaluated using the japanese version of the attitudes toward suicide questionnaire.resultsthe mean age of the subjects was 25.24.0 years old . \n the majority of the participants in our study agreed that anyone could commit suicide ( 88.8% ) and that suicide is preventable ( 86.3% ) . after adjusting for age and sex , multivariate regression analysis revealed that maternal care approached a statistically significant association with the right to suicide attitude . under the same conditions , \n maternal care was shown to be significantly associated with the common occurrence attitude . \n no other significant relationships were observed between parental bonding and attitudes toward suicide.conclusionthis study suggests that a higher level of maternal care ensures that children think that suicide occurs less commonly . \n the promotion of best practices for suicide prevention among medical students is needed . \n child rearing support might be associated with suicide prevention .", "id": 906} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe evaluation of vibration sensation informs the clinician about the integrity of mechanoreceptors in the skin , rapidly conducting large - diameter afferent fibers in the peripheral nerves and the dorsal column - medial lemniscus pathways in the central nervous system [ 1 , 2 ] .\ntherefore , diminished vibration sensation is an important finding in the diagnosis of disorders affecting the dorsal column - medial lemniscal system and may also be an early sign of peripheral neuropathies .\nit is known in everyday practice that patients , due to the physical properties of this sensory modality , can perceive vibration through layers of clothes .\nthis recently resulted in a debate during a case presentation in our clinic in which one of the authors tried to perform the examination on a clothed subject for the sake of speed .\nthe present study was designed under the inspiration of this dispute with the hope of providing some new insights into the characteristics of vibration sensation .\nfifty healthy volunteers ( h group ; median age was 37 years , 22 male ) and 19 patients with diabetic polyneuropathy ( pnp group ; median age was 57 years , 5 male ) were included in the study ( table 1 ) .\nthe h group mainly consisted of volunteer relatives of patients , healthcare professionals , and medical students stratified into 4 age groups , as follows : ages 1825 ( n = 14 ) , 2640 ( n = 13 ) , 4155 ( n = 13 ) , and 55 + ( n = 10 ) .\ntheir mean height was 168.5 9.1 cm ( range 153 to 183 ) and their mean weight was 72.2 14.6 kg ( range 49 to 110 ) . a brief neurological examination including superficial sensation , muscle strength , and tendon reflexes was made and found to be normal in all the subjects in this group .\nthose who had any neurological and systemic disease or who were using medications which could affect the peripheral or central nervous systems were excluded from the study .\nthe pnp group consisted of patients with known type 2 diabetes mellitus and the clinical diagnosis of diabetic polyneuropathy visiting the diabetic outpatient clinic for their regular controls ( median follow - up duration was 14 years ; range 126 ) .\nvibration sensation was measured with the common psychophysical technique , whereby the duration of vibration sensation is dependent on each subject 's judgment .\nthe subjects lay supine in a comfortable quiet room with an ambient temperature of 2025c during the measurements .\na 128 hz standard tuning fork was used to assess the vibration sensation throughout the study ( riester tuning fork w / clamps , aluminum , no .\n5162 , c 128 hz , california , usa ) . the socks used in this study all had the same thickness and tissue characteristics ( the same model from a certain manufacturer ; cotton , 70 denier linear mass density ) which had been purchased in bulk and were disposed of after a single use . \nfour sites were selected for measurements : dorsum of the interphalangeal joint of the great toe ( gt ) and the vertex of the medial malleolus ( mm ) on both sides .\nthe tuning fork was applied vertically to these points with gentle pressure after the prongs were maximally activated ( by tapping the prongs against the examiner 's hypothenar eminence ) for each measurement ( figure 1 ) .\ntwo investigators took the measurements ; the first one applied the tuning fork while the second investigator measured with a stopwatch the duration of vibration sensation from the activation time of the tuning fork until the subject 's verbal indication that the sensation was over .\nthose who were found to have no vibration sensation at all on any of the measurement sites ( usually at gt ) were excluded from the study at this point . in the measurement phase ,\n2 measurements without and 2 measurements with socks were performed on each site in the following sequence , allowing a five - minute break inserted so as not to exhaust the subjects and to help them maintain their concentration : without , with , interval , with , without .\nsixteen measurements in total were taken for each subject , requiring about 20 minutes for the entire procedure .\nthe averages of each pair of measurements with and without socks were used as the statistical input . \nthe procedure was approved by the istanbul faculty of medicine ethics committee ( 2012/1244 ) and all participants provided informed consent .\nall the statistical analyses were performed using the statistical package for the social sciences ( spss ) , version 17.0 , for windows ( spss , chicago , il , usa).samples were tested for their distribution with kolmogorov - smirnov test.correlations between the measurements in the same conditions ( first and second measurements on the same side without socks and with socks ) and between the measurements on both sides were tested with pearson 's r.after showing a high correlation between the items in , the results of the two measurements for each condition and the results elicited on the right and left sides were averaged to constitute the main inputs for the statistical analyses .\nthe difference between the mean durations of vibration sensation without and with socks in both groups was analyzed using paired samples t-test.statistically significant results elicited in were analyzed for the effect size , using cohen 's d.in the h group , correlations of vibration sensation with age , height , and weight were assessed with pearson 's r.independent samples t - tests were performed to evaluate the difference between the vibration sensations measured at the gt and mm.differences between the results elicited in the pnp group and those found in an age - matched subgroup of h ( 13 females and 9 males , aged 40 years ( median 53 , min 40 , max 68 ) ) were analyzed with independent samples t - tests .\ncorrelations between the measurements in the same conditions ( first and second measurements on the same side without socks and with socks ) and between the measurements on both sides were tested with pearson 's r. after showing a high correlation between the items in , the results of the two measurements for each condition and the results elicited on the right and left sides were averaged to constitute the main inputs for the statistical analyses . \nthe difference between the mean durations of vibration sensation without and with socks in both groups was analyzed using paired samples t - test .\nstatistically significant results elicited in were analyzed for the effect size , using cohen 's d. in the h group , correlations of vibration sensation with age , height , and weight were assessed with pearson 's r. independent samples t - tests were performed to evaluate the difference between the vibration sensations measured at the gt and mm .\ndifferences between the results elicited in the pnp group and those found in an age - matched subgroup of h ( 13 females and 9 males , aged 40 years ( median 53 , min 40 , max 68 ) ) were analyzed with independent samples t - tests .\nthe mean durations of vibration sensation and the differences between the results elicited without and with socks are given in table 1 .\nthe effect of wearing socks was found to be insignificant except that found on the mm in the h group , which was seen to have a small effect size upon further analysis with cohen 's d < 0.2 ( d = 0.17 ) . vibration sensation was found to decline with age in the h group for two measurement points and both conditions .\npearson 's r in measurements without socks were 0.502 ( p < 0.001 ) and 0.432 ( p = 0.001 ) , and with socks were 0.467 ( p = 0.002 ) and 0.416 ( p = 0.003 ) , respectively ( figure 2 ) .\nthe duration of vibration sensation was shorter at the mm as compared to gt in the h group ( the mean difference was 4.3 s , p < 0.001 ) . a smaller difference in the same direction was also observed in the pnp group ( 1.5 s mean difference , p = 0.012 ) ( figure 2 ) .\nthe vibration sensation of only one of the 50 participants in the h group , a 68-year - old male , measured less at the gt than at the mm , whereas 3 patients in the pnp group were found to have shorter vibration durations at the gt . as compared to the age - matched subjects from the group h , the duration of vibration sensation in the pnp group had a significantly shorter vibration duration at the gt but not at the mm measurement points ( p < 0.01 and p = 0.12 , resp . ) .\nthe present study reveals that the mean durations of vibration sensation measured without and with socks are nearly the same ; there is practically no difference between them in normal subjects and patients with diabetic polyneuropathy .\nalthough a statistically significant reduction with socks was found in the measurements at the mm in group h , its effect size was small and the mean difference was less than one second . since clinicians generally express the duration of vibration sensation by whole seconds , without using fractions , the size of the difference found at the mm does not seem important enough to affect the results of clinical examination . as far as we know , this is the first study on humans to investigate the perception of vibration over clothing .\nother examples of clinical studies which investigated the effect of clothing during physical examination do exist , including the auscultation of lung sounds through thin clothing and measurement of blood pressure through sleeves using the auscultatory method .\nthese studies all resemble each other in that the focus of interest is sounds and vibrations and the spectrums in question are also similar .\nkraman showed that lung sound perceived by stethoscope was somewhat deteriorated by one or two layers of indoor clothing but this effect can be reduced by force on the stethoscope head .\nliebl et al . did not found statistically significant difference between sleeved and nonsleeved arm during manual auscultatory sphygmomanometric and automatic oscillometric blood pressure measurement .\nan everyday experience was also found to be congruent with these results , that of a vibrating cell phone .\nit was observed that one is easily able to perceive the vibrations of a cell phone in her / his pocket through a significant amount of clothing . with this observation in mind , we measured the frequencies of incoming call vibrations of several models of cell phones and found that the range was 116 to 250 hz .\nit is not surprising that this range includes the optimum frequency range for pacinian corpuscles , namely , between 60 and 400 hz .\nall these data suggest that the interference from garments on vibration energy is little . with regard to the vibration of a cell phone in vibration sensing , the use of a pager device in its vibration mode was reported to be used for clinical vibration testing in an era when cellular phones were not so common .\nthe tuning fork is the most readily available instrument in daily clinical practice for measuring vibration sensation and is sufficiently reliable when compared to other techniques of measurement [ 7 , 8 ] .\nseveral studies report the use of the rydel - seiffer graduated 64 hz tuning fork because of its semiquantitative properties [ 79 ] .\nalthough one was available at the installation phase of the present study , it was discarded because the semiquantitative scale of this device seemed to provide insufficient time resolution for our requirements .\nthe other reason for discarding this tuning fork was that its 64 hz was thought to be in the preferential frequency range of meissner 's corpuscles rather than the pacinian afferents .\nthe physiology of pacinian corpuscles may play a critical role in the sensation of vibration through clothing , due to their subcutaneous localization and wide field of perception [ 1 , 10 ] .\nthe shorter vibration durations at the mm than at the gt are an unexpected finding for clinicians familiar with axonal polyneuropathies , due to the distal to proximal progression of degeneration .\nit has been concluded that substantial tissue damping affects the tuning fork while taking measurements at the mm .\nthis is probably caused by the solid mass of the tibia which is substantially larger than that of the toe bones beneath the gt measurement points .\nwe think that the shorter vibration durations at the mm can be attributed to this phenomenon , which has been analyzed in detail in the article by goldberg and lindblom .\nmean vibration duration at the gt was higher than that at the mm even in the pnp group , although the difference was less . this may be due to the fact that this study involved only mild to moderate cases of diabetic pnp and excluded the more advanced cases in whom vibration sensation was measured as totally absent distally .\nit might be expected that , with more advanced disease , the gt measurement would have been able to exceed the mm in shortening of vibration sensation duration due to the distal axonopathy process . in conclusion\n, this study shows that no practically significant difference arises from wearing socks when measuring vibration sensation with a tuning fork ; any interference thus caused is negligibly small .\nthis is true for the healthy population over a wide age range and also for patients within the clinical context of a diabetic polyneuropathy .\nhowever , this study does not aim to recommend measuring vibration sensation over socks . in the patients with chronic polyneuropathy ,\ncareful examination of the feet is crucial for the screening of ulcers and infections and leaving the socks in place during examination is strongly discouraged .\nbesides , the socks would still have to be removed in order to perform the other modalities of neurological examination . bearing these in mind , we hope that the results of the present study will be considered as a clinical clue indicating one of the remarkable properties of vibration sensation .", "answer": "objective . to investigate the difference between the measurement of vibration sensation without and with socks . \n material and methods . \n fifty healthy volunteers ( h group ) and 19 patients with diabetic polyneuropathy ( pnp group ) were included . \n the sites of measurement were the great toe ( gt ) and medial malleolus ( mm ) . \n a standard 128 hz tuning fork was used in the measurements . \n results . \n mean duration of vibration sensations without and with socks was as follows : in the h group , 19.4 4.2 and 19.5 4.2 s at gt and 15.1 3.3 and 14.6 3.3 s at mm ; in the pnp group , 13.4 3.8 and 12.7 4.1 s at gt and 11.9 3.8 and 11.7 3.4 s at mm . \n no significant difference was found between the measurements without and with socks , except those found at the mm in group h ( p = 0.02 ) . \n this significant difference was further analyzed in terms of effect size which was concluded to be practically insignificant ( cohen 's d < 0.2 ) . \n shorter mean vibration duration was measured at mm as compared to gt that could be explained by the damping effect . \n conclusions . wearing socks of moderate thickness \n does not have any important effect on the duration of vibration sensation . \n this might be considered as a reflection of the remarkable properties of vibration sensation .", "id": 907} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe name granulosa cell tumor ( gct ) was proposed by von werdt in 1914 .\nto have primarily originated retroperitoneal gct is even rarer . in medical literature in english from 1938 till today , only 12 cases have been reported .\nalthough , the histology of ovarian adult - type granulosa cell tumors ( agcts ) is well - documented , it is rarely encountered in cytological specimens and the identification of tumor cells is very difficult . here\n. per abdominal examination revealed a well - defined mass palpable in the left hypochondriac and lumbar regions . computerized tomography ( ct ) of the abdomen revealed a solid heterogeneous mass lesion measuring 11.2 cm 8 cm 12 cm , consistent with retroperitoneal hematoma [ figure 1a ] .\nultrasonography ( usg)-guided aspiration of the mass was performed and the smears were hypercellular with small , overlapping cell clusters and cells in a microfollicular pattern [ figure 1b ] .\non enquiry , she gave a history of hysterectomy with bilateral salpingo - oophorectomy 22 years ago for uterine leiomyoma .\nwith these cytological features and the clinical history , a diagnosis of extraovarian agct was proposed .\nwe received multiple dark brown and necrotic tissue fragments together measuring 10 cm 8 cm 3 cm .\nthe cut section of all fragments showed gray white , yellowish , and hemorrhagic areas .\n( a ) ct showing a solid heterogeneous mass in the left anterior pararenal space compressing left kidney ( b ) cytology smear showing cells in microfollicular pattern ( papanicolaou , 400 ) ( c ) cells in sheets and microfollicular pattern ( h and e , 400 ) ( d ) tumor cells showing strong positivity for inhibin ( inhibin , 400 ) histologically the neoplasm was composed of small round to oval neoplastic cells with predominantly microfollicular [ figure 1c ] , diffuse , and watered - silk patterns .\nimmunohistochemistry ( ihc ) for inhibin and epithelial membrane antigen ( ema ) was done .\nthe tumor was positive for inhibin [ figure 1d ] and negative for ema . with the typical histopathological features and ihc findings , a diagnosis of primary agct of retroperitoneum was confirmed .\nthere are two subtypes : adult and juvenile , based on different clinical and histological features .\nagct of the ovary is oftentimes a hormonally active stromal cell neoplasm that is distinguished by its ability to express aromatase and to secrete sex steroids such as estrogen .\nthe histogenetic origin of extraovarian agct is thought to be from the ectopic gonadal stromal tissue from the mesonephros .\nthe cytological smears of an agct are usually highly cellular of both single cells , syncytial aggregates , and follicular pattern\n. the cells are monomorphic with scanty to moderate amount of pale cytoplasm and monomorphic round to oval nuclei having longitudinal grooves and granular chromatin .\nhistologically , the tumor cells resemble normal granulosa cells with uniform , round or oval nuclei having finely granular chromatin and longitudinal nuclear grooves or folds .\nthey show microfollicular , macrofollicular , trabecular , watered - silk , or diffuse patterns .\nextraovarian gct should be differentiated from other tumors such as small - cell carcinoma , undifferentiated carcinoma , carcinoids , and lymphoma .\ngct is positive for inhibin and calretinin and negative for ema whereas other tumors do not show positivity for inhibin and calretinin .\nthe case of primary retroperitoneal gct is reported for its rarity after excluding previous ovarian origins and to describe its relevance to the histologic origin . due to their rarity , agcts present a diagnostic challenge for cytologic preparations .\nwe believe that sensitive cytologic evaluation , histopathologic correlation , taking clinical history , and a positive immunohistochemical reaction with inhibin could help us in practice .\nsurgery is the primary treatment for these tumors , however , long - term follow - up with history , clinical examination , and tumor markers are crucial for gcts , as later relapse is a common behavior for these unique tumors .", "answer": "the most frequently occurring retroperitoneal tumors are those of the kidneys , adrenal glands , and the pancreas . \n a primary retroperitoneal tumor composed of granulosa cells and developing far away from the normal location of the ovary is less frequently observed . \n a 69-year - old female patient presented with abdominal discomfort . computerized tomography ( ct ) of the abdomen revealed a solid heterogeneous mass lesion measuring 11.2 cm 8 cm 12 cm consistent with retroperitoneal hematoma . \n ultrasonography ( usg)-guided aspiration smears revealed cytological features suggestive of adult - type granulosa cell tumor ( agct ) . as the patient had a history of hysterectomy with bilateral salpingo - oophorectomy 22 years ago for leiomyoma , a diagnosis of extraovarian agct was made . \n intraoperatively , the tumor was removed in piecemeal that showed yellowish areas with extensive necrosis and hemorrhage . \n histopathological examination of the excised mass and inhibin positivity confirmed the diagnosis . \n primary retroperitoneal extraovarian gct is a rare tumor with only 12 cases reported in medical literature in english .", "id": 908} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalthough global gene content and detailed sequence similarity comparisons with the previously described megaviridae members clearly classify pgv within the family ( including the partially sequenced organic lake phycodnaviruses ( olpv ) , chrysochromulina erecina virus , and phaoecystis pouchetti virus ) , the finding of a pgv - associated virophage came as a surprise .\ncomplete virophage genomes have now been described , but only 3 correspond to identified and isolated \nthe pgv virophage ( pgvv ) is the third , and presumably not the last , of a rapidly growing series . except for their genome size in the 20 kb range ,\nthese new types of satellites viruses have little in common in terms of gene content , although they all code for a major capsid protein and one dna primase .\nconsistent with the fact that it was never observed in pgv - infected cultures , pgvv is the first example of a virophage lacking the information to make a capsid protein , the essential building block of a virus particle . once multiplied in the pgv virus factory , the pgvv genome is thus packaged ( in multiple copies ) alongside the pgv genome , and propagated through the pgv virion , either as an integrated or free viral plasmid . the precise molecular structure(s )\nthe finding of a virophage associated to pgv is already teaching us the important lesson that virophages are not solely associated to dna viruses with micron - sized particles and 1 mb genome sizes , but can be found with large dna viruses of more reasonable ( poxvirus - like ? ) proportion .\nit is thus likely that many of such associations have been overlooked in the past , and that virophages might have played a fundamental role in the evolution of many more viruses than just the megaviridae .\nif this is true , they could be ( and have been ) the main vehicle of gene transfers between eukaryotic viruses , and indirectly between these viruses and their hosts .\nthey may also be responsible for the sporadic occurrences of mobiles elements such as self - splicing introns , inteins , and transpovirons .\nanother lesson is that , like all parasites , the virophages are submitted to the irreversible phenomenon of reductive evolution , condemning them to disappear as individual biological entities , eventually saving some of their genes by integrating them into the genome of their companion virus , themselves undergoing a similar process vis - - vis their cellular host .\nthe first published phylogenetic tree including mimivirus 2 and using a concatenation of 7 universally conserved protein sequences , already pointed out that : we could now build a tentative tree of life , within which mimivirus appears to define a new branch distinct from the three other domains . elsewhere in the same article , mimivirus was also shown to be part of the broad family of the nucleocytoplasmic large dna viruses ( ncldv ) , branching near the middle of the previously defined iridovirus , phycodnaviruses , poxviruses , and asfarviruses lineages . put together , these 2 results suggested in a subliminal way that all the large dna viruses were in fact defining a domain distinct from the 3 established cellular domains . as additional genomes of megaviridae became available ,\nmolecular phylogenies computed with an increasing number of universal proteins associated to basic functions ( dna clamp loaders , ribonucleotide reductases , aminoacyl - trna synthetases , dna polymerases ) kept clustering the megaviruses in their own clade , clearly separate from the cellular domains , thus contributing an additional domain rooted in between archaea and eukarya in the tree of life . despite receiving increasing support from various authors , others remain strongly opposed to this view . in agreement with the notion of a fourth domain of life anchored by the largest dna viruses , the dna polymerase of pgv nicely clusters with the other megaviridae homologs , exhibiting no affinity with any of the main cellular lineages ( fig . 1 ) .\nbased on the presence of a vestigial protein translation system , i previously argued that the genome of today 's giant viruses derived from an ancestral cellular organism through the irreversible process of reductive evolution experienced by all parasites .\ndna viruses exhibiting a whole range of genomic complexity could have been generated through this continuous process : viruses would have lost translation first ( the ribosome ) , then transcription ( the rna polymerase ) , then dna replication ( the dna polymerase ) , following an evolutionary scenario whereby they become increasingly dependent from their host .\nthe vast range of size and complexity among today 's dna viruses might thus be the results of differences in their evolution rates ( the largest ones experiencing the least evolutionary pressure ) . in this context\n, the lack of affinity of the giant viruses with any of today 's cellular domains , as well as the huge proportion of the viral genes without cellular homolog , would suggest that the lineage of the ancestral cellular organism that gave rise to giant viruses became extinct as a cellular life form , and only managed to survive as a parasitic fourth domain .\n the recently described giant pandoravirus might represent an independent instance of the same scenario .\nthe tree was produced using the default option on the mafft server ( url : mafft.cbrc.jp ) from the multiple alignment of 25 dna polymerase b sequences ( 510 ungapped positions , excluding the inteins ) .\nbranches with bootstrap values < 80 are collapsed . despite infecting eukaryotic hosts from vastly divergent phyla\n, the viruses do not show any phylogenetic affinity with a specific eukaryotic group , and cluster ( in red ) separately from the 3 cellular domains : eukarya ( green ) , archaea ( purple ) , and eubacteria ( blue ) .\nthis strongly supported topology suggests that the common ancestor of the megaviridaelargely predated the radiation of the eukaryotes .", "answer": "the viral nature of the first giant virus , mimivirus , was realized in 2003 , 10 y after its initial isolation from the water of a cooling tower in bradford , uk . \n soon after its genome was sequenced , the mining of the global ocean sampling environmental sequence database revealed that the closest relatives of mimivirus , only known to infect acanthamoeba , were to be found in the sea . \n these predicted marine mimivirus relatives remained elusive until 2010 , with the first genomic characterization of a virus infecting a heterotrophic unicellular eukaryote , the microflagellate grazer cafeteria roenbergensis . \n the genome analysis of a virus ( pgv ) infecting the common unicellular algae phaeocystis globosa now shows that it is a bona fide member of the mimivirus family ( i.e. , the megaviridae ) , extending the realm of these giant viruses to abundant blooming phytoplankton species . despite its smaller genome size ( 460 kb encoding 434 proteins ) \n , pgv exhibits the most intriguing feature of the previously characterized megaviridae : an associated virophage . \n however , the 19-kb virophage genome , devoid of a capsid gene , is packaged in the pgv particle and propagated as a viral plasmid , the first ever described . \n the pgv genome also exhibits the duplication of core genes , normally present as single copies and a putative new type of mobile element . \n in a dna polymerase phylogeny including representatives of the three cellular domains , pgv and the other megaviridae cluster into their own clade deeply branching between domains archaea and eukarya domains , thus exhibiting the topology of a fourth domain in the tree of life .", "id": 909} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe use of robotic - assisted laparoscopic surgery in minimally invasive gynecology has been rapidly increasing since the da vinci robotic platform ( intuitive surgical inc , sunnyvale , ca , usa ) was approved for this purpose by the food and drug administration in 2005 .\nthe rate of robotic hysterectomy is estimated to have increased from as low as 0.5% in 2005 to as high as 22% in 2010 .\nthis technology addresses the ergonomic challenges of traditional laparoscopy by providing a 3-dimensional view , wristed instruments , and diminished tremor for more precise movements , and potentially offers more patients the benefits of laparoscopy , including shorter hospital stays , decreased intraoperative blood loss , faster recovery , and decreased wound infections . as robotics represents an increasing percentage of minimally invasive procedures in gynecology , the debate over the relative benefits of robotic vs conventional laparoscopic surgery is driven by questions of cost , safety , credentialing , and medicolegal issues .\nrobotic surgery presents surgical teams with a radical departure from the operating room ( or ) culture of open surgery and even conventional laparoscopy .\nthe large footprint of the platform and its complexity changes the demands on the or team and may adversely affect efficiency .\nteam members are separated in space and lack face - to - face communication . teamwork and communication have been highlighted as 2 essential components of or safety . to date , few studies have investigated the inherent communication challenges in robotic surgery .\nthe purpose of this study was to evaluate the association between the quality of communication and surgical outcomes , specifically operative time , blood loss , and perioperative complications .\nwe conducted a prospective questionnaire - based pilot study from march 1 through may 31 , 2013 , at a university - affiliated tertiary care medical center .\nsurgeons , circulating nurses , and surgical technicians involved in robotic gynecologic surgery were invited to participate .\nthe anesthesia team was excluded because of frequent personnel turnover during case assignments , precluding adequate study participation .\nall participants signed an informed consent and were assigned a study identification number by the study administrator to maintain anonymity .\ncirculating nurses and surgical technicians assigned to those cases were core members of the robotic surgical team .\nminimally invasive surgery fellows and obstetrics and gynecology residents were also involved in the study .\nall robotic gynecologic surgeries for benign indications during the study period were included . at the end of each surgery\nthe survey was based on 2 validated questionnaires : the safety attitudes questionnaire and the psychometric testing of interpersonal communication skills questionnaire .\nwe focused on the following aspects : individual communication skills , teamwork , efficiency , and provider satisfaction .\nin addition , participants were asked to identify the major factors affecting communication during the case : noise level in the or , console - to - bedside communication problems , lack of nurse availability , lack of instrument availability , lack of participant familiarity with the procedure , other , or none .\nin addition , operative details and outcomes were gathered , including estimated blood loss ( ebl ) , operative time , and perioperative complications .\nstatistical analysis was performed using sas 9.3 ( sas institute , inc . , cary , nc , usa ) .\nin addition , to assess the overall perception of the quality of communication , we subjected the 13 survey questions to a principal component analysis , creating a composite quality of communication ( cqoc ) score .\nmultivariate linear regression models were used to assess the relationship of cqoc to surgical outcomes . in the absence of prior similar studies , a sample size could not be determined a priori .\nthirty - two or team members participated in the study , and 108 surveys were completed .\nthe average response rate was 60% ( 105/174 ) , with a lower rate in fellows ( 9/22 ; 41% ) and a higher rate in circulating nurses ( 34/43 , 79% ; p = .025 ) .\nresponse rates stratified by professional category n , total number of participants per professional category . significance attributed to the difference in response rate between fellows and circulators only .\na total of 24 hysterectomies , 11 robotic myomectomies , 3 sacrocolpopexies with or without hysterectomy , 1 advanced endometriosis resection , and 1 trachelectomy were included in the study .\nspearman correlation between individual quality - of - communication survey items and surgical outcomes showed few significant associations .\nhigher quality - of - communication scores on the item , others misunderstood me because they misinterpreted my words or actions , correlated with a longer room - in to room - out time ( p < .01 ) .\nsimilarly , higher scores on the item , i asked others to repeat themselves because i did n't understand / hear their message the first time , correlated with a greater ebl ( p < .05 ) .\nanalysis of the cqoc score showed an association between the quality of communication in the or and both cut - to - close time and ebl , when controlling for body mass index , prior abdominal surgery , type of procedure , and uterine weight in separate multivariate linear regression models .\na higher cqoc score was significantly associated with a greater ebl ( p = .010 ) and a longer operative time ( p = .045 ) .\nthe coefficients presented in table 3 demonstrate that for every 1-sd increase in the perceived deficit in quality of communication , there was an additional 51-ml of ebl and a 31-min increase in operative time .\ncorrelation between quality of communication and surgical outcomes nonstandardized coefficients of correlation . controlled for body mass index , prior major abdominal surgery , and uterine weight .\nwe compared how the different team members judged the quality of communication in the or , and we found that , for most questions , surgeons rated communication to be worse than did circulating nurses and surgical technicians . for example , surgeons agreed with the statement , steps took longer than necessary because i or others had to repeat / clarify what they were saying , at significantly higher rates than did nurses and surgical technicians ( mean 1.4 , sd 0.6 vs. 0.8 , sd 0.8 ; p < .001 ) . despite a difference in mean cqoc scores between surgeons vs. circulating nurses and surgical technicians\n, both groups ' responses showed that higher cqoc scores were associated with a longer operative time and a greater ebl .\nthe most commonly reported factors that negatively affected the quality of communication were the following : the noise level in the or ( 28/36 ; 78% ) , console microphone / console - to - bedside communication ( 23/36 ; 64% ) ; and the lack of familiarity of participants with the procedure ( 22/36 ; 61% ) ( table 4 ) .\nthere was no significant difference between team members ' report of factors that negatively affect the quality of communication .\nthere were a total of 5 perioperative complications : 1 cystotomy , 1 conversion to laparotomy , 1 suspected postoperative transient ischemic attack , and 2 readmissions for postoperative abscesses .\nhowever , we did not find any associations via logistic regression between cqoc and perioperative complications , ( p > .999 ) .\nfactors affecting communication at least 1 participant reported the issue as occurring in each case .\nwe present an evaluation of the association between the quality of communication and surgical outcomes in robotic surgery .\nour study demonstrated that poor quality of communication is associated with a longer operative time and a higher ebl .\nour survey was based on 2 validated questionnaires including both experienced and inexperienced team members .\nour results illustrate the complexity of communication in the robotic or and demonstrate for the first time the differences encountered in the perception of communication between team members stratified by their role .\nrobotic surgery has introduced unique and novel challenges to the workflow of a surgical team that have never been experienced before . the surgeon and surgical assistants\nmore specifically , surgeons operate while sitting at the surgeon 's console , and their field of vision focuses on the 3-dimensional viewer . several meters away from the surgeon 's console ,\nthe large robotic patient cart ( the platform that attaches to the patient and holds the operating instruments ) often obscures the surgeon 's view of their assistants at the patient 's bedside . the physical distance and obstacles\ncreate an auditory , visual , and physical barrier between team members , potentially hampering efficient communication .\nsurgical teams have traditionally heavily relied on a multitude of nonverbal communication tools , such as body language and eye contact , to anticipate the next step in the workflow of a given surgery .\nit is not until surgeons encounter auditory , visual , and physical barriers that they realize how much they have been relying on those cues for efficient communication .\ncao and taylor reported that the complexity of the robotic setup causes a communications breakdown in the robotics or and potentially deleterious effects on team function , decision - making , and flow of information .\nthey demonstrated that group tasks were executed with greater efficiency and accuracy in a simulated robotic cholecystectomy in which subjects used scripted speech patterns to communicate with team members .\nwebster and cao concluded that facilitated team communication can ease adaptation to new technologies that disrupt customary workflow .\nour data indicate that decreased quality of communication is attributable to modifiable factors : a high level of noise in the or , problems with console microphone and console - to - bedside communication , and lack of familiarity of participants with the procedure .\nthe high level of noise in the room may result from both the substantial background noise generated by the vision console and team members speaking loudly to communicate across significant distances .\nthe current built - in da vinci audio system available may not address properly the communication challenges experienced by team members .\nengineering solutions to these communication barriers may decrease provider mental load and improve surgical outcomes .\nour data suggest a direct relationship between the team members ' experience and quality of communication .\nwhen nurses and trainees who are inexperienced in robotic procedures participate in these cases , it may negatively affect team functioning .\nadoption of systematic approaches to integrating new team members into the robotic or may avoid deleterious consequences caused by poor team dynamics .\nthere is an expanding body of literature on evaluating the effect of these modifiable factors on teamwork , communication , and provider mental load based on the assumption that suboptimal working environment may affect surgical outcome .\nthe current study demonstrated that this assumption has merit . recognizing the importance of further defining this relationship , randell and colleagues are undertaking a large - scale study to understand and improve communication and teamwork in robotic surgeries .\nfinally , our study showed that , not only did both surgeons and nurses share the same perception regarding teamwork , but surgeons were more critical of team performance .\nprior studies evaluating attitudes regarding patient safety in the or have shown that nurses tend to be more critical than physicians and that physicians have a tendency to have limited insight regarding their team members ' perception of performance , safety , and teamwork .\nthe finding in our study that surgeons are more critical or concerned than nurses regarding team integration may reflect a loss of sense of control experienced by the robotic surgeon , located distant from the patient and the rest of the team .\nit was 1 institution 's experience and had a small sample size , thus limiting the generalizability of the data .\nwhereas response rate differed by type of participant and may represent response bias , there were no significant differences in the perception of communication , stratified by role .\nalthough we can not determine a cause - and - effect relationship , this study does establish a clear relationship between the complexity of surgery and poor communication in robotic gynecologic surgery and provides a rationale for further comprehensive study .\nmore objective methods of assessing communication effectiveness , such as videotaped analysis , can be employed in addition to subjective assessment in future studies .\nour study demonstrated that the diminished quality of communication reported by or team members is associated with more adverse metrics of patient outcomes .\nambient noise , audio clarity , and team members ' inexperience , all contributed to lower communication scores . overcoming the communication and teamwork obstacles introduced by robotic surgery may increase patient safety .\nfuture studies are needed to assess interventions for improvement in communication and teamwork in the robotics or .", "answer": "background and objectives : robotic surgery has introduced unique challenges to surgical workflow . \n the association between quality of communication in robotic - assisted laparoscopic surgery and surgical outcomes was evaluated.methods:after each gynecologic robotic surgery , the team members involved in the surgery completed a survey regarding the quality of communication . \n a composite quality - of - communication score was developed using principal component analysis . \n a higher composite quality - of - communication score signified poor communication.objective parameters , such as operative time and estimated blood loss ( ebl ) , were gathered from the patient 's medical record and correlated with the composite quality - of - communication scores.results:forty robotic cases from march through may 2013 were included . \n thirty - two participants including surgeons , circulating nurses , and surgical technicians participated in the study . a higher composite quality - of - communication score \n was associated with greater ebl ( p = .010 ) and longer operative time ( p = .045 ) , after adjustment for body mass index , prior major abdominal surgery , and uterine weight . \n specifically , for every 1-sd increase in the perceived lack of communication , there was an additional 51 ml ebl and a 31-min increase in operative time . \n the most common reasons reported for poor communication in the operating room were noise level ( 28/36 , 78% ) and console - to - bedside communication problems ( 23/36 , 64%).conclusion : our study demonstrates a significant association between poor intraoperative team communication and worse surgical outcomes in robotic gynecologic surgery . employing strategies to decrease extraneous room noise , \n improve console - to - bedside communication and team training may have a positive impact on communication and related surgical outcomes .", "id": 910} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncardiovascular disease accounted for 30 % of an estimated 58 million deaths globally from all causes in 2005 .\nit is important to recognise that a substantial proportion of these deaths ( 46 % ) occurred in individuals under 70 years of age , in their productive years of life ; in fact , 79 % of the disease burden attributed to cardiovascular disease is in this age group .\nmoreover , between 2006 and 2015 , deaths due to non - communicable diseases ( half of which are due to cardiovascular disease ) are expected to increase by 17 % .\nthis projected increase is most prominent in asia due to a very large , ageing population , increasing exposure to a westernised diet , and rapidly increasing rates of diabetes mellitus .\nearly detection of patients at risk and early institution of effective treatment may help to ease the mortality and morbidity burden of cardiovascular disease . to achieve this ,\nimproved early diagnosis in patients with chest pain in or before the emergency department would reduce the burden on the hospitals .\nfurthermore , in an ageing population with improved outcome after myocardial infarction , the number of patients with an elevated risk for a second cardiovascular event is increasing but identification of patients at high risk of recurrent events remains difficult .\nincreasing survival following acute coronary events also leads to more patients living to develop heart failure ( hf ) .\nhf , the final common pathway of cardiac insults , is a serious syndrome due to inability of the heart to provide adequate circulation for the body s needs or only able to do so at increased cardiac filling pressures .\nit is the cardiovascular syndrome projected to increase most in the usa with the largest attendant loss of productivity and increase in direct medical cost in the next 20 years .\neurope and asia show similar data [ 5 , 6 ] , with a rapid increase in disease burden on society .\nevidence - based therapy of proven efficacy has been introduced over the last 25 years but mortality and readmission rates remain high .\nthese vesicles are important in cell to cell communication in a variety of processes including coagulation , antigen presentation and tissue damage .\nplasma extracellular vesicles can be easily isolated from frozen plasma or serum and contain protein , mirna and rna depending on source and stimulus .\nextracellular vesicles that play a role in the initiation of thrombus formation are of major interest in cardiovascular disease pathogenesis , since thrombosis is the major underlying cause of cardiovascular events . in this process ,\ntissue factor ( tf ) , as an important initiator of thrombosis , was found in vesicles that are positive for the monocyte marker cd14 ( fig . 1 ) .\nin vitro studies using endothelial cells ( ec ) showed that these tf - containing vesicles do not only initiate thrombosis but also adhere to the ec that results in increased ec thrombogenicity via elevation of tf activity in the ec and decrease of tissue factor pathway inhibitor and thrombomodulin .\nthis procoagulant activity , with monocyte - derived circulating tf as its main source , was associated with coronary artery disease and in stent thrombosis .fig .\nsubpopulations of extracellular vesicles ( evs ) in the plasma involved in coagulation are thought to have three origins : monocyte - derived evs ( blue ) , platelet - derived evs ( red ) and endothelial cell - derived evs ( green ) as outlined in the enlarged ev 3-colour pie chart .\nfor coagulation tf is the key initiator of the coagulation cascade and forms a complex with factor viia ( fviia ) .\nthe activated factor x ( fxa ) further cleaves prothrombin into thrombin that converts fibrinogen into fibrin to form clot . for fibrinolysis\n, the plasmin inhibitors serping1 and serpinf2 have been identified in evs and inhibit the breakdown of a fibrin via fibrinolysis .\nabbreviations : ev , extracellular vesicle ; tf , tissue factor ; psgl-1 , p - selectin glycoprotein ligand-1 ; ps , phosphatidylserine ; p - sel , p - selectin ; e - sel , e - selectin diagram showing an overview of the potential plasma extracellular vesicle procoagulant activity .\nsubpopulations of extracellular vesicles ( evs ) in the plasma involved in coagulation are thought to have three origins : monocyte - derived evs ( blue ) , platelet - derived evs ( red ) and endothelial cell - derived evs ( green ) as outlined in the enlarged ev 3-colour pie chart .\nfor coagulation tf is the key initiator of the coagulation cascade and forms a complex with factor viia ( fviia ) .\nthe activated factor x ( fxa ) further cleaves prothrombin into thrombin that converts fibrinogen into fibrin to form clot .\nfor fibrinolysis , the plasmin inhibitors serping1 and serpinf2 have been identified in evs and inhibit the breakdown of a fibrin via fibrinolysis .\nabbreviations : ev , extracellular vesicle ; tf , tissue factor ; psgl-1 , p - selectin glycoprotein ligand-1 ; ps , phosphatidylserine ; p - sel , p - selectin ; e - sel , e - selectin if extracellular vesicle proteins are involved in cardiovascular events , then plasma vesicle protein content might be an important biomarker source for prognosis and prediction of cardiovascular events .\ncirculating mirnas are , at least partly , derived from extracellular vesicles and have been used in the diagnosis of acute coronary syndrome ( acs , ) .\nextracellular vesicle protein levels , however , have only recently been described to carry information in the presence of acs . following a proteomics discovery approach\n, we demonstrated in a chest pain cohort of 471 patients that pigr , cystatin c ( cst3 ) , c5a and total vesicle protein concentration are associated with the presence of acs .\ncomparisons of this association between male and female patients reveal these markers to be highly associated with acs in males but not with acs in females .\nthis striking difference is in agreement with an increasing body of evidence that women tend to have lower rates of coronary artery occlusions and have a more preserved left ventricular function .\nwomen , however , also have a higher mortality and a worse prognosis following mi compared with men .\nthe established difference in extracellular vesicle protein levels associated with acs identifies vesicles as an excellent biomarker source for gender - specific diagnosis and prognosis of acs .\nfurthermore , this might help in understanding the underlying gender differences in the pathophysiology of acs .\nthe number of survivors of a first cardiovascular event is on the rise globally with a rapid increase in asia .\nthese patients are at high risk for a second cardiovascular event even after adequate control of risk factors .\nthe number and type of extracellular vesicles that are cd31/annexin v positive were associated with an increased risk for secondary events consisting of myocardial infarction , percutaneous coronary intervention ( pci ) , coronary artery bypass graft ( cabg ) , stroke and vascular mortality .\nfor the first time , the protein content of all plasma extracellular vesicles and its association with secondary cardiovascular events were studied in a large clinical cohort . comparing plasma extracellular vesicles of patients with a secondary cardiovascular event to gender- and age - matched patients without a second cardiovascular event\nthese vesicle proteins were cystatin c , serping1 , serpinf2 and cd14 and were validated in the smart cohort .\nthis revealed that three of these vesicle proteins ( cystatin c , serpinf2 and cd14 ) were associated with future cardiovascular events after correction of risk factors such as age , gender , smoking and egfr .\nfor this , measurement of plasma extracellular vesicle protein levels has the potential to stratify patients at risk for secondary events on top of risk factors .\nthere is much uncertainty over the relative contribution of platelets to the overall circulating extracellular vesicle population .\nplatelets are a key intermediary in the blood extracellular vesicle landscape because their function is readily and rapidly modified by platelet - directed medications .\nthe ongoing stratifying risk with metabolomics and platelet reactivity testing in acute coronary syndrome ( smart - acs ) study , initiated in singapore , includes platelet reactivity testing of more than 1000 patients undergoing invasive management of acs , using impedance aggregometry ( multiple electrode aggregometry , roche diagnostics , indianapolis , in ) and follow up for secondary cardiovascular events .\nthis will allow us to investigate how platelet - directed medications may potentially modify the content of the plasma extracellular vesicle population and its association with secondary events .\nthe identification and validation of new biomarkers is highly dependent on the availability of patient cohorts with detailed phenotypic characterisation .\nimportant ethnic differences have been described in the susceptibility , risk factors , and outcomes with cardiovascular disease .\nfor example : indian men in the uk have an adjusted hazard ratio of 1.45 ( ci : 1.29 to 1.63 ) for cardiovascular disease while chinese men in the uk have an adjusted hazard ratio of 0.51 ( ci : 0.32 to 0.83 ) compared with caucasian men . among southeast asian patients with hf in singapore , indians and malays have been shown to suffer worse outcomes than chinese although the reasons remain unclear .\nthe adhere - asia pacific registry showed that compared with other multicentre registries in the us and europe , asian patients hospitalised with hf were younger and had more severe clinical features .\nfor this , we initiated the ( ongoing ) biobanking efforts in both singapore and the netherlands ( fig . 2 ) . in 2008 , the design of the atheroexpress collecting tissue , plasma and blood cells with a follow - up for secondary cardiovascular events was used to start up the singapore atheroexpress at the national university heart center singapore ( nuhcs ) .\nthis singapore biobank is collecting , besides atherectomy samples , also aortic punctures during cabg next to plasma and blood cells , and follows patients up for secondary cardiovascular events .\naortic punctures and plasma are now also collected at the umc utrecht in pegasus using the same design.fig .\nred boxes indicate matched biobank studies , green boxes indicate work in progress of matching singapore and dutch biobank studies , numbers indicate patients included ~ june 2013 overview of ongoing cardiovascular biobanking in singapore and the netherlands .\nred boxes indicate matched biobank studies , green boxes indicate work in progress of matching singapore and dutch biobank studies , numbers indicate patients included ~ june 2013 singapore initiated the collection of plasma of patients undergoing a pci with follow - up for secondary cardiovascular events .\na year later , the umc utrecht mirror biobank of pci patients was initiated , a collective effort that now includes over 1000 patients a year .\nwork is in progress to match patients with chest pain in the emergency department of the meander hospital in amersfoort ( minerva biobank cohort ) with chest pain cohorts at nuhcs and singapore general hospital as well as the extensive hf cohort initiatives in singapore and asia with dutch heart failure cohorts . a key advantage of these mirrored cohorts is the implementation of common data and tissue collection and storage protocols across sites in both countries .\nthis facilitates comparisons of biomarker profiles between dutch and singapore populations ; such an effort is currently ongoing , with measurement of high sensitivity troponin t , high sensitivity c - reactive protein , von willebrand factor , myeloperoxidase and cystatin c in 1200 dutch and 1000 singaporean patients who have undergone elective coronary angiography .\nplasma extracellular vesicle proteins are still in the early stage of study , mostly aiming to identify and to characterise the proteomes .\nalthough relatively unexplored due to technical challenges , vesicle proteins hold promise as mass spectrometry - based proteomic technology is rapidly emerging for identification and quantification of extremely low abundant proteins in a sample .\nthis has already resulted in identification of vesicle proteins for the diagnosis of acs and prognosis of secondary cardiovascular events in clinical cohorts .\nisolation of plasma extracellular vesicle subpopulations is expected to lead to new and better cardiovascular vesicle protein biomarkers in a new sample set .\nthis rapidly growing vesicle technology will hold , in combination with the maturation of the biobanks ( inclusion of patients and secondary events ) in the netherlands and asia , great promise for new diagnostic and prognostic biomarkers that take ethnicity and gender into account .", "answer": "cardiovascular disease is a major public health problem worldwide . \n its growing burden is particularly ominous in asia , due to increasing rates of major risk factors such as diabetes , obesity and smoking . \n there is an urgent need for early identification and treatment of individuals at risk of adverse cardiovascular events . \n plasma extracellular vesicle proteins are novel biomarkers that have been shown to be useful in the diagnosis , risk stratification and prognostication of patients with cardiovascular disease . \n ongoing parallel biobank initiatives in european ( the netherlands ) and asian ( singapore ) populations offer a unique opportunity to validate these biomarkers in diverse ethnic groups .", "id": 911} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 28-year - old healthy male was seen in our clinic complaining of vision loss in his right eye ( od ) .\nbest - corrected visual acuity ( bcva ) was od : 20/200 and left eye ( os ) : 20/20 .\nmild vascular abnormalities were detected in the temporal aspect of right optic nerve , but no conclusive information was obtained .\noct using the stratus oct 3 model ( carl zeiss meditec , jena , germany ) was indicated for the evaluation of the macular areas , rnfl thicknesses , and optic nerves .\nthe fast macular protocol revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae .\nno visible alterations in the internal microarchitecture of the retina were observed using several retinal lines and optic disc protocols .\na slight incremental thickening of the rnfl was observed in the superior and nasal quadrants of the os . in order to evaluate the patient 's visual field ( vf ) and retinal sensitivities ,\na frequency doubling technology perimetry ( fdt ) , using the commercially available ( matrix ) device , was performed in both eyes .\nthe threshold 30 - 2 strategy revealed the presence of junctional scotoma composed by a central scotoma in od associated with superior temporal quadrantanopia in the fellow eye . the pattern detected in the vf suggested the presence of an expansive mass at the level of the optic chiasm [ fig . 1 ] . magnetic resonance imaging ( mri )\nwas performed which disclosed the presence of a tumor , compatible with the diagnosis of pituitary adenoma [ fig . 2 ] . after a complete neurological evaluation , medical treatment with cabergoline ( a dopamine agonist ) ,\nafter 8 months , a significant reduction of tumor volume was achieved . moreover , the patient experienced a full recovery of bcva and vf [ fig . 3 ] .\nright : superior temporal quadrantanopia in os central nervous system mri . left : pituitary dependent macroadenoma .\nvisual loss associated with a junctional scotoma is a well - known clinical sign related with the presence of a compressive mass in the chiasmal area .\nmonteiro described a generalized reduction of the rnfl thickness in the retinas of patients with band atrophy secondary to pituitary tumors .\nlederer and colleagues reported on the usefulness of the macular map thickness , while studying patients with glaucomatous optic nerve alterations . due to a relative incremental change in the ganglion cells axonal concentration within the macular area\ninterestingly , the patient described here showed a thickening in the nasal and superior and nasal aspects of both maculae .\nthis tomographic sign , not visible on the biomicroscopic fundus examination and in the fa , was interpreted as an early retinal manifestation produced by the presence of the tumor .\nthe physiopathology of this localized , incremental thickness is merely speculative , but could be produced by an alteration in the axonal transport in ganglion cells .\nafter obstruction of the axoplasmic flow , an early enlargement ( intracellular edema ) of the nerve fibers followed by a chronic atrophy could occur . though no direct evidence exists corroborating this phenomenon ,\nat least three indirect clinical issues support this theory : ( 1 ) the retinal thickness increment was revealed anatomically by the oct , but no evidence of dye leakage was seen in the fa .\n( 2 ) the presence of a topographic correlation between the junction scotoma and the macular thickening . ( 3 ) the visual loss was ipsilateral to the main tumor location .\nfurthermore , the macular thickness enlargement was symmetric while the visual alteration was roughly asymmetric .\nthis most likely could be indicative of the potential for intracellular edema preceding the visual function alteration and this thickening could be an early sign that could be detected before consolidated fiber atrophy occurs .\nfrequency doubling technology perimetry ( matrix fdt ) has shown to be a suitable method for studying and detecting abnormalities in patients with neurological visual field deficits . during the functional evaluation of this patient , the fdt revealed the presence of a junctional scotoma compatible with the tumor location .\neven with an asymmetric vf defect , the oct was able to show symmetric involvement , with respect to macular thickness .\nwe speculate that the anatomical alteration revealed by the oct precedes the functional deficit found in the vf .\nthus , we propose that detection of bi - superonasal macular edema ( me ) could be an early sign of chiasmal pathology . with an early diagnosis and subsequent treatment ,\na complete restoration of visual function was achieved in this case , stressing the importance of early recognition of the disease .\nwe are unaware of previous reports regarding localized bi - superonasal me secondary to a pituitary adenoma and could find no references to it in the medical literature .\nstudies including a cohort of patients are warranted for the evaluation of these tomographic findings . in conclusion\n, it is important to suspect pituitary adenoma in cases of vf deficit and oct macular alterations .", "answer": "a 28-year - old healthy male complaining of vision loss in his right eye was discovered to have localized bi - nasal macular edema in the presence of a pituitary adenoma . \n the presence of a junctional scotoma composed by a central scotoma in the right eye associated with superior temporal quadrantanopia in the fellow eye was seen . \n the pattern detected in the visual field suggested the presence of an expansive mass at the level of the optic chiasm . \n optical coherence tomography findings also revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae . \n this report illustrates the importance of suspecting a pituitary adenoma in the light of uncharacteristic retinal alterations .", "id": 912} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\napproximately 24 per cent of small bowel obstructions ( sbos ) are caused by bezoars .\nin addition , presentation with features of acute surgical abdomen is extremely rare , accounting for only 1% of the patients .\na bezoar is a concretion of indigestible material found in the gastrointestinal tract , which usually forms in the stomach and passes into the small bowel , where it can cause sbo .\nit can be classified into one of four major types : trichobezoar , pharmacobezoar , lactobezoar and phytobezoar .\ntrichobezoars are composed of hair and are most commonly associated with patients who have a psychiatric disorder .\nphytobezoars are composed of undigested fiber from vegetables or fruits and are the most common form of bezoar encountered as a postoperative complication after gastric bypass .\na 63-year - old syrian male presented to the emergency department with a 2-day history of generalized colicky abdominal pain associated with repeated vomiting and absolute constipation .\nthere was no associated history of alteration of bowel habit , rectal bleeding , fever or dysuria .\nhis past medical history was significant for a laparotomy in 1979 due to a peptic ulcer - related complication , but he was unaware of the details .\nhe was also recently diagnosed with diabetes mellitus for which he was using herbal treatment consisting of boiled olive tree leaves ( olea europaea ) . on physical examination\nthere was a midline laparotomy scar with a reducible incisional hernia in the epigastric area .\nhe had mild lower abdominal tenderness with no muscle guarding and his bowel sounds were exaggerated .\nrectal examination revealed no abnormalities and there was a small amount of stool in the rectum .\nroutine blood investigation and abdominal x - rays were obtained . apart from leukocytosis , they were unremarkable .\na contrast - enhanced ct scan was arranged and it showed features of sbo with collapse of the terminal ileum .\nthere was evidence of a previous gastrojejunostomy with suspected foreign bodies in the stomach and proximal ileum .\n( figs 1 and 2 ) \n figure 1:contrast - enhanced abdominal ct scan in coronal view showing evidence of gastrojejunostomy and visible foreign body in the stomach and features of small bowel obstruction . \n\nfigure 2:sagittal ct scan view showing foreign bodies in the stomach and the ileum with transition point in the small bowel .. contrast - enhanced abdominal ct scan in coronal view showing evidence of gastrojejunostomy and visible foreign body in the stomach and features of small bowel obstruction .\nsagittal ct scan view showing foreign bodies in the stomach and the ileum with transition point in the small bowel . at laparotomy\nan obstructing hard foreign body was palpable in the ileum with dilatation of the proximal small bowel loops .\n3 ) both foreign bodies were removed through an enterotomy and gastrotomy , respectively , and the bowel was decompressed .\nafter limited adhesiolysis , the abdomen was closed en mass repairing the midline hernia defect . \n figure 3:retrieved phytobezoars . retrieved phytobezoars .\npostoperative recovery was unremarkable except for a short duration of ileus , after which the patient made a steady recovery .\nhe was referred to the diabetology department and dietician during admission and was discharged with outpatient clinic follow - up .\na follow - up upper gi endoscopy was done and it showed evidence of a hiatus hernia with gastrooesophageal reflux disease .\nthe incidence of bezoar formation after gastric surgery ranges from 5 to 12 per cent .\nthe main pathogenesis of bezoar formation is believed to be the result of gastric dysmotility and decreased gastric secretions , which is very common after any gastric surgery [ 3 , 4 ] .\ndiospyrobezoars , formed after persimmon ingestion , are a distinct type of phytobezoars characterized by their hard consistency .\ncoca - cola ingestion combined with endoscopic techniques has been used effectively to treat gastric phytobezoars and avoid surgery .\nphytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen .\nthe presence of a well - defined intraluminal mass with a mottled gas pattern on emergency ct scan is suggestive of an intestinal phytobezoar .\nguidelines include proper chewing of food , plenty of liquids with meals and avoidance of a high - fiber diet .", "answer": "approximately 24 per cent of small bowel obstructions ( sbo ) are caused by bezoars . \n in addition , presentation with features of acute surgical abdomen is extremely rare , accounting for only 1% of the patients . \n a bezoar is a concretion of indigestible material found in the gastrointestinal tract , which usually forms in the stomach and passes into the small bowel , where it can cause sbo . \n we present the case of a 63-year - old male who presented with sbo following ingestion of boiled olive leaves as herbal treatment for diabetes mellitus .", "id": 913} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nprimary infection involves eyes , ears , larynx , lungs , and sinuses , followed by liver , spleen , bone , and meninges .\nworldwide , aspergillus fumigatus is the most common species , followed by aspergillus niger and aspergillus flavus , whereas a. flavus is the most common species in india .\npredisposing factors that promote fungal infections in the sinuses include polyps and stagnant secretions besides other factors like neutropenia , inappropriate use of antibiotics , immunosuppressive drugs , corticosteroids , uncontrolled diabetes mellitus ( dm ) , human immunodeficiency virus ( hiv ) infection , trauma , burns , and radiation therapy . in immunocompromised patients\n, aspergillus leads to highly destructive lesions ; however , literature search shows invasive aspergillosis in non - neutropenic patients also .\nclinico - radiological findings can be misleading as the lesions are locally destructive and mimic a neoplasm .\ninvasive fungal sinusitis ( ifs ) responds to conservative medical management and debridement ; hence , an early diagnosis by fine needle aspiration cytology ( fnac ) is mandatory to prevent undue surgery .\nwe report two patients presenting with swelling and pain in the maxillary region who were clinico - radiologically suspected of malignancy ; however , fnac in both the cases revealed fungal sinusitis ( fs ) .\nfnac was performed in both cases using 22-gauge needle ; aspirate was whitish fluid ( case 1 ) and blood mixed ( case 2 ) .\nthe aspirates were processed as air - dried giemsa - stained smears ; cytomorphological features were suggestive of aspergillosis .\nperiodic - acid - schiff ( pas ) and silver methanamine ( sm ) stains were performed on the aspirate smears for further typing of fungus . however , considering the clinico - radiological suspicion of neoplasm , a biopsy was advised that confirmed fungus in both the cases . a 45-year - old female presented to the ear , nose and throat ( ent ) department with complaints of a painful swelling in the left maxillary region for 6 months .\nthere was no history suggestive of nasal obstruction , fever , recurrent infections or diabetes .\nclinically , there was a tender swelling in the left maxillary region near the medial canthus .\ncomputed tomography ( ct ) scan showed expansion of the maxillary sinus with bone erosion , suggestive of a malignancy . a 42-year - old male presented with complaints of headache , nasal discharge and swelling in right maxillary region for 8 months .\na bony hard swelling measuring 8 8 cm was palpated in the right maxilla reaching up to the infraorbital region .\nct scan showed an enhancing soft tissue density in the right maxillary sinus , suggestive of a proliferative lesion .\nmicroscopic examination of aspirate smears revealed predominantly hemorrhagic background with many multinucleated foreign body giant cells ( gcs ) , and few inflammatory cells comprising eosinophils , plasma cells and lymphocytes . interspersed amongst these and within the gcs ,\nbased on the ct and cytological features , a diagnosis of ifs caused by aspergillus was suggested .\n( a ) smear shows septate , fungal hyphae branching at acute angle in an acute inflammatory background ( giemsa , 250 ) and ( b ) a hyphae within the giant cell ( giemsa , 400 ) histopathological examination of biopsies from the maxillary sinus in both the cases showed abundant septate fungal hyphae , granulomatous inflammation , gcs and eosinophils ; pas and sm stains confirmed the type of fungus as aspergillus [ figure 2 ] .\nculture from the serous material from sinusitis showed greenish white cotton wool growth at 37c on sabouraud 's dextrose agar ( sda ) , thus confirming the species as a. flavus .\nsections show ( a ) aspergillus in necrotic background ( h and e , 250 ) , ( b ) fungal hyphae in giant cell ( h and e , 400 ) , ( c ) many eosinophils and hyphae ( h and e , 250 ) , special stains highlighting the fungal morphology ( d ; pas , 250 ) and ( e ; silver methanamine , 250 ) the former patient was treated initially with intravenous amphotericin - b and endoscopic debridement , followed by oral itraconazole ; further , she had to undergo partial maxillectomy in view of frequent recurrences and bone involvement .\na 45-year - old female presented to the ear , nose and throat ( ent ) department with complaints of a painful swelling in the left maxillary region for 6 months .\nthere was no history suggestive of nasal obstruction , fever , recurrent infections or diabetes .\nclinically , there was a tender swelling in the left maxillary region near the medial canthus .\ncomputed tomography ( ct ) scan showed expansion of the maxillary sinus with bone erosion , suggestive of a malignancy .\na 42-year - old male presented with complaints of headache , nasal discharge and swelling in right maxillary region for 8 months .\na bony hard swelling measuring 8 8 cm was palpated in the right maxilla reaching up to the infraorbital region .\nct scan showed an enhancing soft tissue density in the right maxillary sinus , suggestive of a proliferative lesion .\nmicroscopic examination of aspirate smears revealed predominantly hemorrhagic background with many multinucleated foreign body giant cells ( gcs ) , and few inflammatory cells comprising eosinophils , plasma cells and lymphocytes . interspersed amongst these and within the gcs ,\nbased on the ct and cytological features , a diagnosis of ifs caused by aspergillus was suggested .\n( a ) smear shows septate , fungal hyphae branching at acute angle in an acute inflammatory background ( giemsa , 250 ) and ( b ) a hyphae within the giant cell ( giemsa , 400 )\nhistopathological examination of biopsies from the maxillary sinus in both the cases showed abundant septate fungal hyphae , granulomatous inflammation , gcs and eosinophils ; pas and sm stains confirmed the type of fungus as aspergillus [ figure 2 ] .\nculture from the serous material from sinusitis showed greenish white cotton wool growth at 37c on sabouraud 's dextrose agar ( sda ) , thus confirming the species as a. flavus .\nsections show ( a ) aspergillus in necrotic background ( h and e , 250 ) , ( b ) fungal hyphae in giant cell ( h and e , 400 ) , ( c ) many eosinophils and hyphae ( h and e , 250 ) , special stains highlighting the fungal morphology ( d ; pas , 250 ) and ( e ; silver methanamine , 250 ) the former patient was treated initially with intravenous amphotericin - b and endoscopic debridement , followed by oral itraconazole ; further , she had to undergo partial maxillectomy in view of frequent recurrences and bone involvement .\nfungal sinusitis constitutes 69% of all the rhinosinusitis.[68 ] clinically , it presents as either an acute fulminant sinusitis or chronic invasive sinusitis .\nthe former is largely attributed to mucor and the latter is mainly due to aspergillus .\nthe acute form is a life - threatening condition , usually seen in immunocompromised patients with severe neutropenia or dm , and is associated with significant visual and neurological impairments in survivors , and sometimes mortality .\nclinically , these patients may present with rhinorrhea , headache , nasal obstruction , proptosis , facial and periorbital pain mimicking infections ( mucor , tuberculosis , osteomyelitis ) , inflammatory lesions ( rhinoscleroma , wegener 's granulomatosis ) and malignant tumors of the nose and paranasal sinuses .\nnon - invasive fs includes allergic and fungal ball and does not need extensive surgery , while most of the ifs patients are unresponsive to conservative management and require appropriate antifungals with local debridement .\nearly and definitive diagnosis of ifs is mandatory that will rule out other differential diagnoses , especially neoplasm , and will help clinicians for appropriate management and in the follow - up of patients .\nboth magnetic resonance imaging ( mri ) and ct can help establish a diagnosis of ifs .\nbone involvement and erosion is more delineated on ct , while soft tissue extensions , vascular invasion and cavernous sinus involvement are more appreciated on mri . both the imaging techniques , however , are not definitive and often fail to differentiate an infectious process from a neoplastic one . definite diagnosis of fs depends upon the demonstration of the fungus on aspirate smears or a biopsy .\nfungal culture is complimentary to morphology and required for species identification ; but samples submitted for culture may not be representative , and not all the fungi grow on culture media .\naspergillus can be easily differentiated from mucor on morphology , as the latter is characterised by broad , non - septate hyphae branching at right angle . in the present cases ,\nboth the patients were immunocompetent , middle aged and clinico - radiologically suspected of malignancy ; however , they were diagnosed on fnac as fungal sinusitis and prevented from undue surgery .\nspecies identification is not much relevant in patients management , but is of epidemiogical significance , since it depends upon various geographical locations , thus aiding diagnosis in difficult cases .\nthis report emphasizes on the early diagnosis of ifs , which can be managed conservatively preventing the morbidity and mortality in these patients .\ncytology , being an easily available , minimally invasive and inexpensive procedure , can be used as initial diagnostic modality in cases of ifs .", "answer": "fungi have emerged as important etiological agents for chronic sinusitis . \n invasive aspergillosis has been reported in immunocompromised individuals or diabetics ; however , it is uncommonly seen in immunocompetent patients . \n definitive diagnosis of these lesions is based on histological examination and fungal culture . \n we report two cases of invasive maxillary lesions in immunocompetent patients , clinically suspected of malignancy ; however , fine needle aspiration cytology showed fungal hyphae , morphologically suggestive of aspergillus , which was later confirmed on histopathology . \n aspiration cytology thus plays a crucial role in the early and definitive diagnosis of fungal sinusitis in cases clinico - radiologically suspected of malignancy . \n an early diagnosis will help the clinician for early and appropriate management and follow - up in order to decrease the high morbidity and mortality associated with it .", "id": 914} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nchildhood constipation is a common complaint accounting for 3% of visits to pediatricians and 10 - 25% of visits to pediatric gastroenterologist[13 ] .\ncommonly there is no underlying organic cause and the constipation is indentified as functional or idiopathic[4 , 5 ] .\nfunctional constipation is identified by rome iii criteria in children over 4 years old and adolescents having two months of at least 2 or more of the following conditions : 2 defecations in the toilet per week , 1 episode of fecal incontinence per week , history of retentive posturing or excessive volitional stool retention , history of painful or hard bowel movements , presence of a large fecal mass in the rectum , history of large diameter stools that may obstruct the toilet .\nchildren usually are treated with a combination of toilet training , running a bowel diary , and oral laxatives such as paraffin oil . in many patients\nthere are many articles on the efficacy of probiotics in organic and functional gastrointestinal disorders .\nprobiotics are live microbial food ingredients which are reported to be effective in the treatment of many forms of gastrointestinal disorders[812 ] .\nprebiotic is a selectively fermented ingredient that changes the composition and/or activity of the intestinal microflora and has shown beneficial effects in host 's health .\n, we aimed to determine the therapeutic effect of synbiotics ( combination of probiotics containing strains of l. casei , l. rhamnosus , s. thermophilus , b. breve , l. acidophilus , b. infantis , and fructooligo - saccharide as prebiotic ) on childhood constipation .\nthe study was performed at children 's medical center in tehran , iran , from january to december 2009 .\nchildren with constipation were referred to the pediatric gastroenterology clinic for evaluation and treatment of constipation .\none - hundred two children aged 412 years with chronic functional constipation enrolled in this study , were divided into 3 groups by simple randomization method .\nexclusion criteria were organic causes for constipation such as hirschsprung 's disease , spina bifida occulta , hypothyroidism , cystic fibrosis , neurologic abnormalities and intestinal pseudo - obstruction .\nthese patients were excluded from the study by history and physical examination and rome iii criteria of childhood constipation .\nthe research protocol was approved by the medical ethics committee of tehran university of medical sciences .\nlabel of drugs was replaced by a new label indicating drug a or b. contents of sachets or bottles were not known to the physicians or nurses involved in the study .\ngroup a received 1.5 ml / kg / day oral liquid paraffin plus placebo , group b received 1 sachet synbiotic per day ( restore 1x10 cfu/1 sachet , protexin co , uk ) .\nsynbiotic combination consisted of probiotic strains containing l. casei , l. rhamnosus , s. thermophilus , b. breve , l. acidophilus , b. infantis , fructooligosaccharide as prebiotic , and placebo .\ngroup c received 1.5 ml / kg / day oral liquid paraffin and 1 sachet synbiotic per day .\nall patients in the 3 groups received drugs in bottles and sachets with similar shape , taste and color .\nfrequency of bms , stool consistency , number of fecal incontinence , episodes of abdominal pain , painful defecation per week and side effects were determined in each patient before and after treatment .\nsuccess treatment was defined as 3 bms per week , 2 incontinence per month and no abdominal pain .\nstudy design : from seven days prior to study and during the treatment period all children were requested to record frequency of bms , number of fecal incontinence episodes , stool consistency , abdominal pain , painful defecation and effects such as vomiting , diarrhea and oil seepage in a bowel diary . before starting treatment ,\nall children were examined and patients with fecal impaction received rectal enema ( paraffin oil 1530ml / year ) once daily for three days in order to accomplish rectal disimpaction .\ntoilet training consisted of sitting on the toilet 3 times per day for 5 minutes after each meal .\npatients were not allowed to use any other kind of medication for constipation during the study period .\nclinical efficacy was recorded , patients were seen at the end of 4 weeks , and their charts were reviewed .\noutcome measures : primary outcome measures were frequency of bms per week , stool consistency , fecal incontinence episodes per week , presence of abdominal pain , and painful defecation ; secondary outcomes were success treatment and incidence of adverse effects such as vomiting , diarrhea and seepage .\nstool consistency was rated by the patients as hard , normal or watery . statistical analysis : data of baseline information were analyzed with the spss ( ver .\ncontinuous variables were expressed as mean ( sd ) , and categorical data were shown as frequency and percent .\nnumber of bms and fecal incontinence episodes in baseline information were analyzed by kruskal - wallis test .\nchange of frequency of bms and fecal incontinence episodes were analyzed by non - parametric paired wilcoxon test . for assessment changes of stool consistency and abdominal pain between baseline and after treatment , the mcnemar test was used .\ntotally , 102 children ( aged 412 years ) with chronic functional constipation enrolled in this study and were divided into 3 groups .\nfive patients were lost to follow - up and remaining 97 patients consisted of 47.4% males and 52.6% females with a mean age of 6.32.1 years .\nas shown in table 1 , no significant differences were found with respect to demographic data and recorded baseline characteristics between the three treatment groups .\ncharacteristics of the patients and the main outcomes are summarized in table 1 and 2 . as shown in table 2 ,\nthe frequency of bms per week increased in all groups , the highest rise occurring in group c ( p=0.03 ) .\nimprovement in stool consistency and decrease in number of fecal incontinence episodes happened in all groups ( p=0.2 , p=0.3 respectively ) without any statistically significant difference .\nalso , abdominal pain and painful defecation per week decreased ( p=0.6 , p=0.9 respectively ) similarly and there was no statistically significant difference between groups .\nno side effects were reported in group b but in group a 18 patients and in group c 21 patients had seepage ( p<0.001 ) .\ntreatment success in group a was 24/29 ( 82.8% ) , in group b 22/31 ( 71.0% ) and in group c 28/37 ( 75.7% ) without statistically significant difference between them ( p=0.6 ) . \n \nnew investigations have shown that gut bacterial colonization has an important role in health and disease .\nthere are several hypotheses about the effectiveness of this microbial flora in treatment of constipation . according to some\ninvestigations gut microbial flora in chronic constipation is different from that in healthy persons[17 , 18 ] .\nshort chain fatty acids produced by probiotics reduce colon ph and by this mechanism enhance colon motility and finally transit time will decrease .\nthere are a few rcts about probiotics in the treatment of constipation in children . in rcts study by banaszkiewicz and szajewska\nit was concluded that l. rhamnosus \n gg was not an effective adjunct to lactulose in treating constipation in children .\nbu et al evaluated the effect of l. casei rhamnosus \n lcr35 compared to magnesium oxide(mg0).comparisons of the frequency of defecation , consistency of stool and the use of lactulose or enema during the period of treatment were made among the groups .\nthe patients who received mgo or probiotics had a higher defecation frequency , percentage of treatment success ( defined as 3 spontaneous defecations per week with no episodes of fecal soiling ) and less hard stool .\nthere is no statistically significant difference in efficacy between mgo and lcr35 , but less abdominal pain occurred when using lcr35 . in a study by coccorullo et al\nthe beneficial effects of l. reuteri ( dsm 17938 ) in infants with functional chronic constipation was evaluated .\nadministration of l. reuteri had a positive effect on bowel frequency , even when there was no improvement in stool consistency and episodes of inconsolable crying episodes .\nfor example , in children with constipation defined according to the rome iii criteria , administration of bifidobacteria ( b. bifidum , b. infantis , b. longum ) and lactobacilli ( l. casei , l. plantarum , l. rhamnosus ) to 20 children aged 416 years resulted in an increased frequency of bowel movements , a decreased number of fecal incontinence episodes , and reduced abdominal pain , although there was no change in stool consistency .\nit seems that our study is the first rct study which investigates the synbiotics effects in childhood constipation . according to our study , mixtures of different strains of probiotics and their specialized prebiotics are more effective than each of them alone and this combination augments their efficacy in all parameters of study , but in previous researches improvement had been seen only in some of symptoms and signs .\nalso adjunctive therapy of synbiotic and liquid paraffin could be more effective to improve bms than any of them alone .\naccording to this rct , synbiotic have got beneficial effects on symptoms of childhood constipation similar to liquid paraffin without any side effects and synbiotic is an effective adjunct to liquid paraffin to improve bms .", "answer": "objectiveconstipation is a common problem in children . \n there is some clinical evidence for the role of probiotics and prebiotics in the treatment of constipated children . \n this is the first study on the therapeutic effect of synbiotics ( combination of probiotics and prebiotic ) in treatment of childhood constipation.methodsin a double - blind randomized placebo controlled study 102 children aged 412 years with functional constipation were assessed according to rome iii criteria for 4 weeks . \n they were divided into 3 groups : group a , received 1.5 ml / kg / day oral liquid paraffin plus placebo , group b , 1 sachet synbiotic per day plus placebo and group c , 1.5 ml / kg / day oral liquid paraffin plus 1 sachet synbiotic per day . \n frequency of bowel movements ( bms ) , stool consistency , number of fecal incontinence episodes , abdominal pain , painful defecation per week , success of treatment and side effects were determined in each group before and after treatment.findingsthe frequency of bms per week increased in all groups ( p<0.001 ) , but it differed between groups and was higher in group c ( p=0.03 ) . \n stool consistency increased and number of fecal incontinence episodes , abdominal pain and painful defecation per week decreased in all groups similarly and there was statistically no difference between them . \n no side effects were reported in group b ; the main side effect in group a and c was seepage of oil ( p<0.001 ) . \n treatment success was similar in all groups without any significant difference between them ( p=0.6).conclusionthis study showed that synbiotics have positive effects on symptoms of childhood constipation without any side effects .", "id": 915} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe interventions for carotid artery stenosis , vein graft and acute myocardial infarction could embolize a large amount of plaque debris , especially unstable , ulcerative , and thrombus containing lesions ( 1 ) . distal protection devices such as filterwire ex\nhave been widely used in carotid artery stenting to prevent distal embolization of plaque debris ( 2 ) .\nthe large amount of atherothrombotic debris entrapped in the filter could reduce or stop antegrade flow and may be shown as no reflow phenomenon in case using filter type distal protection device .\nwe present a case of pseudo no - reflow phenomenon after postdilatation of the stent in severe carotid artery stenosis and successful recovery with aspiration thrombectomy using export aspiration catheter .\na 70-yr - old man was diagnosed with asymptomatic carotid artery stenosis during preoperative risk assessments .\nhe had been treated in our hospital for congestive heart failure and stable angina for 2 yr .\ncarotid angiogram showed no significant stenosis in the left carotid artery and a 90% stenosis in the right internal carotid artery ( fig .\nshuttle sheath ( 7f , cook medical , bloomington , in , u.s.a . ) was positioned to right common carotid artery via right femoral artery . to prevent distal embolization of plaque debris during angioplasty ,\nfilterwire ex ( boston scientific , natick , ma , u.s.a . ) was positioned in the right cervical internal carotid artery distal to stenotic lesion .\nafter predilation with 4.0 mm balloon , 8 mm self - expanding wall stent ( boston scientific ) was positioned across the lesion and was deployed in stenotic lesion .\nafter postdilation of the stent with 6.0 mm balloon , carotid angiogram showed abrupt complete flow interruption ( fig .\nwe decided to perform aspiration thrombectomy using export aspiration catheter ( medtronic ave , santa rosa , ca , u.s.a . ) ( fig .\nafter several passes of export aspiration catheter into the basket ( over the filterwire ex ) , antegrade flow was fully restored ( fig .\n3 ) . after retrieval of filterwire ex , whitish debris was noted within the basket ( fig .\nthe patient complained of slight speech disturbance and this neurological abnormality was completely recovered within 24 hr after stenting .\nobstructive carotid artery lesions are known to contain friable , ulcerated and thrombolic material that have the potential to embolize during intervention and may be responsible for the majority of the neurologic events during carotid artery stenting ( 1 ) .\na number of \" distal protection \" strategies , designed to capture embolic debris released during carotid intervention , have been evaluated for their efficacy in minimizing the risk of embolic neurologic events .\nthe intravascular filter type distal protection device offers the advantage of a constant cerebral perfusion during carotid artery stenting and allows more time for careful and precise intervention ( 2 ) . during carotid artery stenting using filter type distal protection device , microscopic particles larger than the size of the filter pores ( 80 to 130 m ) could be captured .\n( 3 ) reported that carotid artery stenting with filter type distal protection device experienced flow impairment due to filter obstruction in 7.9% of procedures , which was resolved in all cases after filter removal . in our case ,\nwe suspected this pseudo - no - reflow phenomenon was induced by obliteration of filter pore by massive atherosclerotic debris .\nwe considered to remove filter by retrieval catheter , however , this process may cause entrapment of filter device to retrieval catheter and embolize massive amount of atherosclerotic debris . therefore , we choose aspiration thrombectomy using export aspiration catheter . after aspiration thrombectomy , flow interruption in the right internal carotid artery\nwas completely restored , therefore , we confirmed this phenomenon as pseudo - no - reflow phenomenon instead of true no - reflow phenomenon .\nyadav ( 4 ) recommended practically in his review paper if there is no forward blood flow during carotid angioplasty with filter type distal protection device , this should be aspirated before the filter is collapsed .\nour case is the first case report of pseudo - no - reflow phenomenon in carotid artery stenting using filter type distal protection device and successful recovery of this phenomenon by aspiration thrombectomy using export aspiration catheter .\n( 5 ) recently reported that successful management of pseudo - no - reflow phenomenon by the export aspiration catheter in ostial saphenous vein graft intervention using filterwire ex protection . in conclusion\n, the large amount of atherothrombotic debris entrapped in the filter during carotid intervention could stop antegrade flow .\nthis phenomenon is pseudo - no - reflow phenomenon instead of true no - reflow phenomenon .", "answer": "distal protection devices such as filterwire ex have been widely used in carotid artery stenting , however , the large amount of atherothrombotic debris entrapped in the filter could reduce or stop antegrade flow . \n we present a case of pseudo - no - reflow phenomenon after postdilatation of the stent in a patient with asymptomatic carotid artery stenosis . \n after several passes using an export aspiration catheter , normal flow in the internal carotid artery was restored . \n aspiration thrombectomy can successfully recover pseudo - no - reflow phenomenon .", "id": 916} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfalls of the elderly always lead to serious health issues as the decline of their physical fitness .\nfracture is the most common injury in fall of an elderly and there is also a certain possibility to get coma , brain trauma , and paralysis . at most fall situations , the fall process is the main source of injury because of the high impact . but sometimes the late medical salvage may worsen the situation .\nthat means the faster the salvage comes , the less risk the elderly will face .\nmems ( microelectro mechanical systems ) sensors have simplified the design and implementation of sensor system .\nlocation based service ( lbs ) makes it more convenient to locate the elderly in health monitoring . beside these\ncameras are distributed at limited space to offer pictures or videos of human activities to implement fall detection algorithm .\nexternal supports such as motion sensors could be used to enhance computer vision based fall detection method , and a data fusion algorithm can operate the validation and correlation among the two subsystems to raise robust performance of fall detection .\nthese computer based methods work effectively in indoor environment , but they are hard to realize in outdoor environment as the deployment of cameras is always limited .\nthere are several kinds of detection methods which differ in constitution of motion sensors and detection algorithms .\na single triaxial accelerometer can provide object 's accelerations in three directions which include the influence of gravity .\nthe influence of gravity or dynamic acceleration is available by using a low pass filter or a high pass filter .\nsome kinds of angular movement information can also be calculated based on the relationship between acceleration components and their vector sum .\na triaxial magnetometer can detect magnetic strength in three directions , and it can also provide angular motion information in the horizontal plane .\nbut the environment magnetic field may disturb the geomagnetic field which reduces the reliability of the magnetometer outputs , for instance , in some steel structure architecture or near some objects with strong electromagnetism . as angular information\ncan also be extracted from accelerometer measurements , a state space filter such as the kalman filter is a commonly used technique to combine angular motion information . beside these , sensors such as barometer can also assist pure motion sensors at human gait recognition .\nbut , in fact , using more sensors means more power consumption , and it is a challenge to design a proper algorithm to fuse different kinds of sensors .\na single triaxial accelerometer is quite enough for human fall detection as sufficient information could be extracted from its measurements .\nbesides this , the accelerometer coordinate does not have to be fixed if only the magnitude of sum vector is needed , and that is quite convenient for wearable application . in this paper , a fall detection system based on a wearable device is developed .\nthe hardware and software realization of the device is mainly based on a single triaxial accelerometer and gps / gsm module .\nthe device uses an efficient fall detection algorithm with less resource and power consumption , which means that it is a proper design for outdoor application .\nthen it will get the elderly 's geographic position and send fall alarm short message to caregivers .\nso the elderly who has fallen can get timely help to minimize the negative influence .\ninformation like linear movements ( e.g. , displacement , velocity , and acceleration ) and angular movements ( e.g. , angle , angular velocity , and angular acceleration ) could be obtained directly or indirectly . beside these\n, frequency domain parameters could be extracted from basic sensor measurements by techniques such as fft and wavelet [ 11 , 12 ] .\nfor single triaxial accelerometer application , accelerations and derived angular parameters could be used as recognition features . fall detection algorithm design\naccording to the recognition feature , fall detection algorithms are classified as threshold based and machine learning based . for threshold\nbased method , threshold of recognition feature is set by the designer before application which makes the algorithm have rapid response and less resource consumption .\nbut the choice of threshold needs both rigorous schemes and adequate experiments . for machine learning based design\n, the classification of fall and normal activities is available with the assistance of technologies such as support vector machine ( svm ) and neural network [ 14 , 15 ] .\nmachine learning assistance may enhance system robustness to some extent , but its algorithm design is always high computing resource consumed which limits its application in wearable device . as the compact wearable device requires low power consumption and a single triaxial accelerometer could provide effective information , threshold based fall detection algorithm will be used in this system . algorithm used in this fall alarm system\nwhen a real fall happens , collision between human 's body and ground will produce obvious peak value at the sum acceleration a which has magnitude as \n ( 1)a = ax2+ay2+az2 , \n where ax , ay , and az present accelerometer measurements of three axes .\nthe system uses the sum acceleration as the first step to distinguish high intensity movements from others .\nbut normal motions such as jumping or sitting also produce peak values , which mean that additional detection features are required .\nas human 's motion has low acceleration , it is feasible to get gravity component in each axis by using a low pass filter . if gravity components could be separated before and after human 's fall , then it is possible to calculate the rotation angle of accelerometer coordinate in 3d space , which is also equivalent to the rotation angle of gravity vector relative to fixed coordinate .\nquaternion is an effective tool to describe rotation movement in human 's gait change which also includes falling .\na quaternion could be described as \n ( 2)q = q0+q1i+q2j+q3k \n which has magnitude as \n ( 3)q = q02+q12+q22+q32 .\nunit quaternion which has magnitude q = 1 can be described as \n ( 4)q = cos2+sin2qxi+sin2qyj+sin2qzk. as shown in figure 3 , rotation angle of q equals . the rotation axis is orthogonal to the rotation plane and its direction is in accordance with right hand screw rule .\nqx , qy , and qz are three components of the unit vector which describes the orientation of the quaternion at the fixed coordinate .\nbesides rotation movement , quaternion can also describe a vector in 3d space , such as the gravity vector g which could be described as a quaternion \n ( 5)g=0+gxi+gyj+gzk.gx , gy , and gz are three components of g which has quaternion magnitude as \n ( 6)g = gx2+gy2+gz2=g . a unit quaternion q is used to describe human 's falling movement , which can also be divided into three rotation quaternions q1\n, q2 , and q3 to simplify the calculation as shown in figure 4 . with the help of gravity vector information before and after human 's falling movement as shown in figure 3 , these three separated quaternions are all available . \n\nq \n 1 could be expressed as \n ( 7)q1=cos12+sin12sini+sin12cosj \n which has rotation angle and rotation axis information as \n ( 8)1=arctangbefore , zgbefore , x2+gbefore , y2,sin=gbefore , ygbefore , x2+gbefore , y2,cos=gbefore , xgbefore , x2+gbefore , y2 .\nquaternion q2 can be calculated as \n ( 9)q2=cos22+sin22k \n which has rotation angle as \n ( 10)2=arctan2gafter , ygafter , xarctan2gbefore , ygbefore , x .\nquaternion q3 is \n ( 11)q3=cos32+sin32sini+sin32cosj \n with rotation angle and rotation axis information as \n ( 12)3=arctangafter , zgafter , x2+gafter , y2,sin=gafter , ygafter , x2+gafter , y2,cos=gafter , xgafter , x2+gafter , y2 .\nthen the rotation of the fall movement can be expressed by quaternion multiplication as \n ( 13)gafter = qgbeforeq=q3q2q1gbeforeq1q2q3 , \n where q=q0-q1i -- q2j -- q3k- is the conjugate quaternion of q. quaternion algebra is normally implemented based on basic matrix algebra .\nquaternion multiplication used above could be realized by matrix multiplication as \n ( 14)qgbefore = mq0gbefore , xgbefore , ygbefore , z = q0q1q2q3q1q0q3q2q2q3q0q1q3q2q1q00gbefore , xgbefore , ygbefore , z .\nthe whole rotation quaternion can also be decomposed as \n ( 15)q = q3q2q1=mq3mq2q1.q1 , q2 , and q3 are all available based on gravity information before and after the falling movement . at last , it is possible to get four elements of quaternion q by the equation above and the rotation angle could be calculated as \n ( 16)=2arctanq12+q22+q32q0 .\nwhen an object is falling , magnitude of will approach 90 which is also a character different from most normal activities .\nthe wearable device will be mounted on human 's waist at first to reflect the motion of human body closely , and the device will record gbefore while the elderly is standing still .\nthere is no special requirement of the device orientation but only keep stationary during the wear .\nathreshold means the threshold of sum acceleration magnitude and tthreshold means the threshold of oscillation time duration after the break of athreshold . when measurements in three different axes have been acquired , the sum acceleration |a| will be calculated .\nwhen a real fall happens , sum acceleration will reach peak value of |a| athreshold . in a real falling\n, the fluctuation of acceleration will stop in time duration tthreshold and then the sum acceleration is |a| g as the elderly will lie on the ground . then the acceleration a is recorded as gafter .\n, the system will consider it as a fall if the rotation angle || 90.\nti 's 16 bits mcu msp430f1611 is used to control the whole system and imply the detection algorithm .\nthe measurement range of accelerometer could be set at 2 g , 4 g , 8 g , or 16 \ng , and the maximal sampling rate is 3.2 khz . as human 's activities are normally at low frequency bands , 100 hz is a proper sampling rate for human fall detection .\nthere is an inner digital filter in adxl345 which could weaken noise and reduce the burden of digital signal processing in mcu to some extent .\nthe measurements will be sent through iic ( interintegrated circuit ) bus communication between the sensor and the mcu .\nsim908 can offer gps and gsm service on serial port communication with mcu , and it can also work in low power mode .\neach hardware component of the wearable device is working under low voltage and the detection algorithm does not need complex calculation resource , so the power consumption of the whole device is quite low .\na 1200 mah , 3.7 v polymer lithium battery is quite enough to provide the need of the wearable device for a couple of days .\nhardware structure of the detection device is shown in figure 6 , and the pcb board prototype is shown in figure 7 .\none of them is the software design in wearable device , and the other is in the caregiver 's handset .\nafter initialization of the system , gbefore would be extracted from acceleration measurements by using a low pass filter when the elderly is standing .\nif a fall has been detected , the wearable device will locate the user and send alarm short message to caregivers immediately .\nif the user withdraws the alarm by pressing a button manually , the device will get back to fall detection state and a short message will be sent to inform the caregivers .\nthere is a url ( universal resource locator ) which links to a web map in the alarm short message .\nthe fall location information will be highlighted on a web map when the caregiver opens this link .\nsystem test of the fall detection system has been conducted based on the system design described above . the sampling rate of accelerometer is set at 100 hz and the measurement range is 16 g with a maximum precision of 4 mg .\nmcu will read raw measurements from sensor 's inner fifo and apply the detection algorithm .\nthe test objects are three different volunteers at the ages of 23 , 42 , and 60 , respectively . based on analysis of these volunteers ' experiment data , athreshold and tthreshold\nare set as 2 g and 2 s , respectively . in order to get g\nwhen standing and lying after the fall , sum acceleration a which has magnitude between ( 1 0.3 ) g and ( 1 + 0.3 ) g will be considered as gbefore and gafter .\nconsidering that the tilt of the ground or the lying posture of the elderly may affect the rotation angle , rotation angle between ( 90 30) and ( 90 + 30) will infer that the elderly has fallen .\nsystem test contains five kinds of activities of daily living ( i.e. , walking , jumping , squatting , sitting , and resting ) and four kinds of fallings ( i.e. , forward , backward , leftward , and rightward ) .\neach kind of motion has been repeated 20 times on each volunteer , and the detection results of the proposed algorithm and an acceleration threshold based algorithm are listed in table 1 . the sensitivity and specificity [ 21 , 22 ] of the proposed system can be got from the test data in table 1 .\ntest results of acceleration threshold based algorithm show lower sensitivity and specificity at 91.6% and 88.7% , respectively . \n\nfigure 9 shows the accelerations in different kinds of fallings which all trigger the fall alarm correctly and the corresponding rotation angles are 91.9 , 100.5 , 104.7 , and 114.1. \n figure 10 shows acceleration during activity of lying down and resting which has rotation angle of 117.0 and similar waveform to falling , but the peak acceleration is much lower .\nthey all do not have rotation about 90 ; even some of the peak values are quite high , so the fall alarm has not been triggered .\nan alarm sms ( short message service ) containing a map url has been received by the handset as shown in figure 12 when a fall has been detected . clicking\nthe url will open a map in web browser on which the fall location will be displayed accurately as shown in figure 13 .\nthis paper developed a fall detection system based on a single triaxial accelerometer based wearable device .\nthere is no special requirement of the device 's mounting orientation because the algorithm does not claim the axes of accelerometer to be fixed strictly .\nthe system has low power consumed hardware design and highly efficient algorithm which could extend the service time of the wearable device .\nas normal activity of resting also has similar rotation as falling , it may trigger fall alarm when the body hits ground heavily .\nso the choice of athreshold is quite important to distinguish falling from heavily lying activity .\nsufficient sample number collected from subjects with different age and gender will improve the reliability and robustness of the threshold . beside these , technologies such as svm and neural network are considerable to seek out a proper classification method based on the features used in this system .", "answer": "fall detection is a major challenge in the public healthcare domain , especially for the elderly as the decline of their physical fitness , and timely and reliable surveillance is necessary to mitigate the negative effects of falls . \n this paper develops a novel fall detection system based on a wearable device . \n the system monitors the movements of human body , recognizes a fall from normal daily activities by an effective quaternion algorithm , and automatically sends request for help to the caregivers with the patient 's location .", "id": 917} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwhen they look at the smartphone screen in this posture for a long time , they experience \n shoulder and neck pain , and occasionally complain of headaches1 .\nwhen continuous loads are applied in a static posture with the head \n kept lowered , musculoskeletal diseases may develop2 .\nthis may lead to myofascial pain syndrome by causing stress and excessive tension in the \n muscles around the neck and shoulders3 . \n\nmyofascial pain syndrome may develop along with tissue damage , or abnormal conditions may \n occur as a result of abrupt stress or excessive tension on the muscles4 .\njobs that require sitting at a desk for long hours , such as computer and office work , \n negatively influence the neck and shoulder muscles5 .\nin addition , changes in the strength of the deep cervical flexors , \n endurance , and the location of the lower jaw have been shown in individuals with neck pain , \n compared with individuals without neck pain6 .\nkieine and schumman studied the activity of the upper trapezius associated with changes in \n shoulder postures , and tepper studied the effects of computer work on the activity of the \n upper trapezius7 , 8 .\nthese studies found that incorrect postures cause excessive tension \n in the upper trapezius and the surrounding muscles .\nsuch excessive tension is known to cause \n pain by developing abnormal forces in the skeletal system9 , 10 .\nthe measurement of cervical - bent postures of women using computers showed increases in the \n head tilting of women complaining of pain11 .\na large proportion of the existing studies have focused on the \n visual display terminal ( vdt ) that is commonly seen with office computers .\nin addition , some \n studies have examined the fatigue and activity of cervical muscles under the postures \n adopted while using a microscope in the workplace as well as the activity of cervical \n muscles while individuals were watching a digital multimedia broadcasting ( dmb ) phone12,13,14 .\nsmartphones and tablets have recently \n drawn a great amount of attention and have become almost daily necessities ; however , these \n devices and other similar new devices may cause cervical deformities when used for extended \n hours . therefore\n, multiple studies on changes in the activity and fatigue of cervical \n erectors in the postures of smartphone users should be conducted in various environments to \n prevent skeletal diseases .\ntherefore , this study was conducted to investigate the changes in \n the activity and fatigue of the splenius capitis and upper trapezius agonistic muscles , the \n muscles that support the head , under the three postures adopted most frequently while using \n a smartphone .\nin this study , the three common postures while using a smartphone were considered as \n independent variables , and the corresponding muscle activity and fatigue as dependent \n variables .\nthe experiment was based on a within - group design in which tests were performed \n on a single group under three different conditions .\nthe subjects were 15 college students in \n their 20s who were given complete explanations about the experiment in advance .\nthe subjects \n were required to be healthy individuals with no history of spinal damage or undergoing any \n surgery , and no hand or wrist injuries or other surgeries during the preceding six months . \n\nall participants were instructed about potential risks and experimental design , and were \n provided with an informed consent form to sign prior to participation , with the knowledge \n that they could withdraw at any time .\ngeneral \n characteristics of the subjects are shown in table \n 1table 1.general characteristics of the subjectsmeanectage ( yrs)23.6 2.4height ( cm)174.7 7.6weight ( kg)69.2 11.9gender ( men / women)8/7 .\nthe muscles targeted for measuring muscle activity were the splenius capitis and upper \n trapezius , which are the agonistic muscles for cervical extension and are known to cause \n neck pain11 , 15 .\nthe researcher identified the location of these muscles by \n activating the areas around the subjects relevant muscles , and then attached electrodes , as \n shown in table 2table 2.locations for attachment of electrodesmusclelocationsplenius capitismidpoint between the spinous process of c7 and the \n peak of the shoulder bladeupper trapeziusthe point 2 cm away from the lateral side of t4 , by referring to previous studies15 .\nthe electrodes were attached after sterilization with alcohol \n would be adequate , and the electrodes were attached after sterilization with alcohol using \n cotton balls .\nthe markers of a three - dimensional motion analyzer were attached to \n objectively determine the maximum cervical bending posture , middle cervical bending posture , \n and neutral posture .\nthe markers were attached to the center of the forehead , the seventh \n cervical vertebra ( c7 ) , and the seventh thoracic vertebra ( t7 ) .\na chair of the same height as that in a subway train was prepared , and each subject was \n instructed to sit in the chair with his or her hips touching the back of the chair and the \n pelvis fixed . in the maximum bending posture ,\nthe subject was instructed to place a \n smartphone as high as the subject s elbow and grab it with both hands 5 cm away from the \n trunk ( fig .\nmaximum bending posture in the middle bending posture , the subject s her upper arms were close to the trunk and the \n neck was bent slightly in a comfortable manner ( fig . \n 2fig .\nthe edge of the upper part of the smartphone s screen and \n the subject s eye level were kept horizontal ( fig . \n\nthe average degree of neck - bending during each of the three postures was obtained \n by measuring and averaging the degrees of the three motion markers for each posture during \n preliminary tests on five subjects .\nthe average degree of neck - bending was 100 for the \n maximum bending posture , 122 for the middle bending posture , and 131 for the neutral \n posture .\na height - adjustable table was prepared to support the subjects arms during the \n postures to avoid fatigue in the arms16 . \n\nsurface electromyography ( semg ) was used to measure the 15 subjects while they remained in \n the three postures , and measurements were performed randomly to reduce errors caused by \n measuring in the sequence of the postures .\nwhile each subject was adopting each posture for \n five minutes , he or she was instructed to continuously type the sentences the blue house is \n not seen from the outside . and\nafter five \n minutes , the subject s muscle activity and fatigue were measured . after being measured under \n one condition ,\neach subject was provided with a 24-hour break to recover from fatigue , and \n then was tested under the next condition17 . in this study , a chair having the same height as that of a seat in \n a subway train and a height - adjustable vibrating table was used .\nthe smartphone used during \n the experiment was one that is commonly used by koreans , and a three - dimensional motion \n analyzer ( smart e , italy ) was employed to measure the degree of bending during each posture . \n\na wireless electrode emg system ( free emg , bte , italy ) was used as an emg device to identify \n the muscle activity and fatigue of the splenius capitis and upper trapezius .\nemg data from \n the maximum cervical bending postures , middle cervical bending postures , and neutral \n postures were applied into root mean square ( rms ) for five minutes , and mean values were \n also calculated for one min and were normalized by % rvc18 .\nmiddle bending posture the study data were analyzed statistically , using spss version 18.0 for windows .\nthe \n kolmogorov - smirnov test was used to confirm that the characteristics of the data used in \n this study represented normal distribution .\nan analysis of variance ( anova ) test was \n conducted to compare the activity and fatigue of the cervical erector during the three \n different postures while using the smartphone .\nscheffe s test was employed as a post - hoc \n test on the statistically significant differences between the muscle groups , and the \n statistical significance level for all data was set at =0.05 .\nin terms of the differences in the muscle activity for each posture , the four muscles \n measured ( right splenius capitis , right upper trapezius , left splenius capitis , left upper \n trapezius ) did not show any statistically significant differences ( table 3table 3.comparison of the muscle activity under the posturesmuscleposturemeanstandard deviationright splenius capitisneutral posture14.27.4middle bending posture13.48.2maximum bending posture 18.825.9right upper trapeziusneutral posture8.95.8middle bending posture5.53.9maximum bending posture 7.15.7left splenius capitisneutral posture14.29.9middle bending posture13.111.0maximum bending posture 13.711.0left upper trapeziusneutral posture7.74.4middle bending posture5.63.9maximum bending posture7.91.2 ) .\nthe comparison of muscle fatigue among the postures showed statistically significant \n differences for the right splenius capitis , left splenius capitis , and left upper trapezius \n ( table 4table 4.comparison of the muscle activity under the posturesmuscleposturemeanstandard deviationright splenius capitisneutral posture0.20.0middle bending posture0.20.0maximum bending posture0.20.0right upper trapeziusneutral posture0.20.0middle bending posture0.20.0maximum bending posture0.20.0left splenius capitisneutral posture0.20.0middle bending posture0.20.0maximum bending posture0.20.0left upper trapeziusneutral posture0.20.0middle bending posture0.20.0maximum bending posture0.20.0values are shown as mean sd , * p<0.05 . significant difference in \n three postures . : significantly different compared with middle bending \n posture . : significantly different compared with maximum bending \n posture . ) .\nvalues are shown as mean sd , * p<0.05 . significant difference in \n three postures .\nthe purpose of this study was to examine changes in muscle activity and fatigue under \n different postures while using a smartphone , because of their rapidly increasing use . in \n particular , polakowska reported that cervical degenerative changes appear due to working \n postures , types of motions during work , and amplitude of vibration ; paccinni et al . reported \n that improper postures are associated with abnormal cervical curvatures19 , 20 .\ntherefore , one \n aim of this study was to provide basic data on correct postures while using a smartphone to \n prevent neck pain and deformation that can occur due to their extended use in undesirable \n postures . in terms of changes in muscle fatigue associated with postural changes during \n smartphone use , this study showed that the maximum bending posture resulted in significantly \n higher levels of muscle fatigue in the right splenius capitis , left splenius capitis , and \n left upper trapezius , compared with middle bending posture .\nthere were no significant differences in muscle activity in the right splenius capitis , \n left splenius capitis , and left upper trapezius among the three postures .\nhowever , there \n was no change in muscle activity because of the experimenter s tension by the awareness of \n experiments was not controlled and the realization of real long - time smart phone use was \n limited by measuring emg signal for short smart phone using time of five minutes21,22,23.this result is consistent with that of \n jung s study , in which during the head - neck bending exercise of the cervical lordosis group , \n kyphosis group , and hyperlordosis group , a comparative analysis was performed on the \n activity of the deep flexor and the sternocleidomastoid using pressure and ultrasonic \n images , and a higher level of pressure led to a corresponding increase in the activity of \n the deep cervical flexor24 .\n, these results may be because muscles exercise their forces in the \n opposite direction to fight opposite movements25 .\nhowever , the results of this study differ from those of some \n previous studies .\nfor example , thuresson compared muscle activity during the cervical \n neutral posture and cervical 20 forward bending posture on the axis of c7t1 , and found a \n higher level of muscle activity during the 20 forward bending . in addition , yoo compared \n muscle activity during the neutral posture and bending posture , and reported a statistically \n significant higher level of muscle activity during the bending posture17 , 26 . according to \n the results of villanueva s study , in which the trunk s movements affected the activity of \n the muscles that surround it , continuous use of smartphone in the present study may have \n caused contractions of muscles in the hands , wrists , and arms .\nthus , muscle activation in \n the cervical erector was not only confined to the cervical area but also spread into the \n hands , wrists , and arms , thereby resulting in no statistically significant changes in muscle \n activity27 . in this study ,\nthe muscle fatigue under the maximum bending posture and neutral posture \n showed similar levels of increases , although this result was not statistically significant . \n\nsome studies have reported that a smaller degree of joint flexion led to a statistically \n significant higher level of muscle fatigue , which may also support the present study \n result28 , 29 .\nin addition , a smaller degree of cervical flexion increases the \n level of head - lowering , and the head is then influenced by gravity to a larger extent30 . here , a larger load is applied to the \n cervical erector to support the relevant position , which may cause increased levels of \n fatigue .\nfirst , the subjects were measured while they were \n using a smartphone for a short time of five minutes ; therefore , the study did not fully \n reproduce the situation of individuals using their smartphones in the subway , which is \n typically for longer periods .\nin addition , the subjects were 15 college students in their \n 20s , and thus , the results derived can not be generalized for various age groups .\nmoreover , \n it was difficult to control the subjects daily activities during the 24-hour break provided \n after each measurement . consequently , a follow - up study should fully reproduce the \n conditions in which individuals use their smartphones on public transportation , and test \n subjects from various age groups for longer durations of smartphone use .", "answer": "[ purpose ] the purpose of this study was to identify changes in the activity and fatigue \n of the splenius capitis and upper trapezius muscles , which are agonists to the muscles \n supporting the head , under the three postures most frequently adopted while using a \n smartphone . [ subjects and methods ] the subjects were 15 college students in their 20s . \n \n they formed a single group and had to adopt three different postures ( maximum bending , \n middle bending , and neutral ) . while the 15 subjects maintained the postures , muscle \n activity and fatigue \n were measured using surface electromyography . \n [ results ] comparison of \n the muscle fatigue caused by each posture showed statistically significant differences for \n the right splenius capitis , left splenius capitis , and left upper trapezius muscles . in \n addition , maintaining the maximum bending posture while using a smartphone resulted in \n higher levels of fatigue in the right splenius capitis , left splenius capitis , and left \n upper trapezius muscles compared with those for the middle bending posture . \n [ conclusion ] \n therefore , this study suggests that individuals should bend their neck slightly when using \n a smartphone , rather than bending it too much , or keep their neck straight to reduce \n fatigue of the cervical erector muscles .", "id": 918} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nameloblastomas are rare benign odontogenic tumours , most commonly found in a patient s lower jaw .\nalthough rarely metastatic , the growth of these lesions can result in defects in the jaw easily destroying surrounding bony tissues .\nfor this reason , the treatment is often excision of the lesion , with wide excision margins , resulting in the absence of a part , or all , of the mandible .\nthe surgical approach for correction of this mandibular defect is often reconstruction of the mandible in view of inserting dental implants at a later date . despite surgical advancements ,\n, bone grafting with non - vascularized bone remains a good option where facilities for soft tissue flaps are not readily accessible .\ncreating an effective wound closure and reducing the incidence of infection is an important stage in the success of the operation , and has been combated here by tissue expanding the submucosa , using osmed pellets , prior to surgery .\nthis is a relatively new technique to the mandibular region and has the potential to revolutionize the success of microsurgeries in this area . in this report\n, i describe a woman who underwent a repair of her mandibular defect by a combination of innovative techniques , in order to reduce the risk of complications and get her back to an aesthetically pleasing level .\na 35-year - old lady presented to the craniofacial surgeons looking for a permanent fixture to the bony defect in her lower - right mandible . in 1991\nshe had her first operation to remove the ameloblastoma and then had it further excised 6 years later due to a reoccurrence .\nthis resulted in an absence of teeth from the canines back and removal of bone down to the inferior alveolar nerve .\nthe patient has since been clear of any further reoccurrences and wears lower dentures for aesthetic reasons .\nshe has no significant past medical history nor family history , nor does she have any known drug allergies .\nshe does not smoke or drink alcohol . on clinical examination , the patient experiences mild parasthesia in the distribution of her right inferior dental nerve , particularly the lateral aspect of the lower lip . on examination ,\nthere is clear absence of teeth on the lower - right side from the canines back ( to include the premolar , molar and wisdom teeth ) and presence of healthy oral mucosa with laxity to move the submucosa medially .\nthere is a loss of the vertical height of the posterior body of the mandible of about 50% and the vestigial remnants of the lingual plate are just palpable and visible on plain radiograph and ct .\nscans show that the superior margin of the resection is well corticated under the inferior dental nerve ( fig . \n, the patient wishes to get dental implants . the surgical approach taken , prior to the implants ,\n( b ) ct scan of head imaging of the patient 's mandibular defect pre - surgically .\n( a ) radiolocal image of patient 's jaw . ( b ) ct scan of head the patient was initially given the option between a bone graft or vascularized tissue ( free fibular flap ) and informed of the complications a bone graft carries a risk of rejection and vascularized tissue needs an increased amount of post - operative care to ensure that the tissue remains vascularized .\nthe patient was not keen on a free flap and given the fact that the bony deformity was < 5 cm , non - vascularized iliac bone graft was deemed to be sufficient to carry out this operation .\nthe first step was achieving significant tissue expansion ( > 2 cm ) using osmed pellets , guided into the submucosa and kept over the alveolar ridge for several months ( fig . \n( c ) osmed pellets before insertion into the submucosa image of patient 's oral cavity during insertion of osmed pellets . ( a ) incisions made in the submucosa .\n( c ) osmed pellets before insertion into the submucosa two months later , the patient underwent the main bulk of her operation .\nthe osmed pellets were removed from the subperiosteum ( fig . 3a and b ) and the iliac bone graft\nwas taken , made up of cortical and cancellous bone and placed to one side ( fig . \nan epidural catheter was placed inside the soft tissue of the graft site and left overnight .\nit had a continuous fusion of a local anaesthetic to improve post - operative pain and encourage early mobilization . \n\n( b ) open site where iliac bone graft is harvested from ( c ) cortical and cancellous iliac bone submucosa after adequate tissue expansion .\n( b ) open site where iliac bone graft is harvested from ( c ) cortical and cancellous iliac bone previously , using ct scans , a titanium construct was made to guide the outline of the bone graft and complete the missing height and width of the mandible .\nonce fitted to the patients jaw , it was packed with the bone graft and screwed down into position ( fig . \na slight groove was made on the mandible to allow space for the inferior dental nerve to lay , so that the construct did not compact the nerve and cause functional problems . \n\nfigure 5:titanium construct packed with iliac bone graft and screwed into position on the lower mandible titanium construct packed with iliac bone graft and screwed into position on the lower mandible to complete the surgery , the periosteum was sutured over the construct and then the buccal muscosa was sutured over again to form a double - layered closure ( fig . \n6a c).the purpose of this was to prevent infection and rejection , by ensuring that there was an increased distance between the foreign object ( titanium construct ) and the outside environment .\nthe dental implants are scheduled to be inserted several months after this operation . \n figure 6:image of patient 's surgical site .\n( c ) image of post - surgical site image of patient 's surgical site .\nbony defects in the maxillofacial area are a huge problem in clinical orthodontics , caused by a wide range of injuries and diseases presenting as either cosmetic or functional defects and in some instances both .\nit is the importance of accounting for the anatomical , functional and aesthetic aspects that make the reconstruction so challenging .\noften patients suffering from ameloblastomas undergo resection as treatment and are left with bony defects that require reconstruction . in this case , the intention was to realize an aesthetically pleasing appearance for the patient and it has been shown that bone grafting with subsequent dental implants is a successful method . as in this case , it is recommended that non - vascularized autogenous bone grafting can be used when a two - layer watertight closure is attainable .\nsources of bone could have been harvested from either local or distant sites but in this case , an extra - oral site ( iliac bone ) was used as a moderate amount of bone was needed .\nthe surgery lasted 5 h and incorporated several novel techniques to improve the outcome of the operation .\nthe use of osmed pellets was innovative , as pellets of this size have only recently been experimented on goats maxilla .\nas well as allowing for space to put the construct , the pellets allowed for a tension - free closure .\notherwise , the result would have been a high - tension closure , leading to rapid breakdown of the graft providing an entrance for infection , a common complication occurring when titanium plates are exposed .\nadvantages of the osmed tissue expanders are that the material is safe with a low complication rate and low risk of infection due to small incision site and minimal trauma .\nthe titanium construct is another relatively novel approach and was invaluable in the success of this surgery , as it guided reconstruction of the mandible , allowing for dental implants to be put in at a later date . at present , an alloplastic material such as titanium is often used for mandibular reconstruction as it is resistant to corrosion , adaptable and biocompatible .\nalthough the insertion of dental implants is the end goal for this surgery , the importance of this case report is to highlight the novel techniques involved in making this surgery a success . the use of small osmed pellets in the submucosa of the mouth to cause sufficient tissue expansion and create a tension - free closure , combined with the titanium construct packed with grafted iliac bone to rebuild the jaw was an approach recommended by the doctors for the repair of bony defects of < 5 cm .\ni suggest prudent management of future cases post - operatively to ensure a continued success of the graft .", "answer": "this case report describes a 35-year - old caucasian radiographer who presented with a significant mandibular bony defect following multiple excisions of an ameloblastoma . as a result , there was an absence of teeth on the lower - right mandible and a clear defect in the mandible . \n the treatment objectives were to rebuild the mandibular defect , with a long - term view of inserting dental implants . in a novel approach outlined in this presentation , tissue expansion of the submucosa , a titanium construct and an iliac bone graft \n were used to rebuild the patient s jaw . \n this surgical technique is recommended for the reconstruction of bony defects .", "id": 919} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsimultaneous occurrence of hashimoto 's thyroiditis ( ht ) , and graves disease ( gd ) is rare .\na 60-year - old lady presented with tremulousness of hands , palpitation , and excessive sweating .\nher weight was 46 kg , bmi 17 , afebrile , regular pulse rate of 110/min with fine tremor in hands .\nthyroid gland was symmetrically enlarged , firm , without any bruit , but mildly tender with lobular surface .\ninitial thyroid function tests ( tft ) revealed : t3 : 3.80 ng / ml ( 0.80 - 2.10 ) , t4 : 12.40 ug / dl ( 5.10 - 12 ) , thyroid stimulating hormone ( tsh ) : 0.20 u / l ( 0.70 - 5 ) .\nher anti thyroperoxidase ( tpo ) antibody : 374 iu / ml ( normal [ nl . ]\n< 35 ) and tsh receptor antibody : 15 u / l ( nl . < 1 ) were both strongly positive .\n99mtc pertechnetate scan showed an enlarged gland with increased uptake of radiocontrast : 17% ( nl .\nthyroid fine needle aspiration cytology ( fnac ) showed sheets of hurthle cells with abdunce of lymphocytes indicating ht .\nrepeat tft , 3 months later showed : t3 : 4.20 ng / ml , t4 : 14.40 ug / dl , tsh : 0.001 u / l , with increased uptake on repeat scan .\nour case of an elderly lady with no eye signs , lobular , firm tender goiter with patchy uptake in both lower poles on tc99 m scan were odd points in diagnosing isolated gd .\nhashimoto 's thyroiditis ( ht ) and graves disease ( gd ) are the two main types of autoimmune thyroid disease .\nht rarely occurs following gd . but combined occurrence of gd and ht are rare .\na 60-year - old lady , presented with tremulousness of hands for 1 month and palpitation with excessive sweating for 3 months .\nshe had a history of weight loss for 6 months , and gradually enlarging neck swelling for 3 years .\nher weight was 46 kg , bmi 17 , afebrile , pulse rate : 110/min / regular , blood pressure : 140/56 mm of hg .\nher thyroid gland was symmetrically enlarged , firm in consistency , nodular / lobular surface and mildly tender without any bruit .\ninitial thyroid function tests ( tft ) revealed high t3 : 3.80 ng / ml ( 0.80 - 2.10 ) , t4 : 12.40 ug / dl ( 5.10 - 12 ) with a low tsh : 0.20\nmu / l ( 0.70 - 5 ) . her tsh receptor antibody ( tsab ) : 25 u / l ( normal [ nl .\n] < 1 ) , anti tpo antibody : 374 iu / ml ( nl . < 35 ) and thyroglobulin antibody : 268 iu / ml ( nl . < 65 ) were all strongly positive .\nultrasonogram of thyroid revealed an enlarged gland with hypoechoic parenchyma with fibrous septa.tc pertechnetate scan ( tc99 m scan ) revealed enlarged thyroid gland with diffusely increased uptake of radiocontrast : 17% ( nl .\nthyroid fnac showed sheets of hurthle cells with abdunce of lymphocytes and sheets of regular follicular cells , indicating ht .\nrepeat tft , 3 months later showed : t3 : 4.20 ng / ml , t4 : 14.40 ug / dl , tsh : 0.001 u .\nrepeat tc pertechnetate scan was done , which again revealed enlarged thyroid gland with diffusely increased uptake of radiocontrast : 21% ( nl .\nour patient presented with clinical symptoms and signs of thyrotoxicosis along with slightly raised t4 , t3 and low tsh with positive tsab , and diffusely increased uptake on tc99 m scan , all in favor of a diagnosis of gd .\nhowever , there were some odd features such as elderly age , absence of eye signs , nodular , firm mildly tender goiter , hypoechoic parenchyma in ultrasonography ( usg ) , and patchy uptake in both lower poles on tc99 m scan .\nfnac of the thyroid gland was suggestive of ut fnac of thyroid gland suggested ht .\nso we adopted a wait and watch policy , and put the patient on beta blockers .\nrepeat tft , 3 months later showed persistent thyrotoxicosis and repeat tc99 m scans revealed an enlarged thyroid gland with diffusely increased uptake of radiocontrast .\ndiffusely increased uptake on tc99 m scan rules out hashitoxicosis , which mostly resolves within 3-months time - frame .\na diagnosis of combined occurrence of hyperthyroid gd and hd was established and anti - thyroid medication started .\nreported four cases of ht in previously diagnosed patients with gd hyperthyroidism . in three cases ,\nht occured 7 - 25 years after gd treatment ; in one , it developed in a few months of gd treatment .\nthe diagnosis of ht was based on clinical manifestation , positive tpo and thyroglobulin antibody , and fnac .\nall were middle - aged women , who had high titers of anti - thyroid antibodies and thyrotoxicosis at the onset of painful ht .\nreported seven patients with hypothyroidism due to hashimoto 's disease , who developed hyperthyroid gd .\nsome had transient , some persisistent hyperthyroidism due to gd following hypothyroidism due to ht .\nht and gd represent the main two types of autoimmune thyroid disease . gd is caused due to hyperplasia and hyperfunction of the thyroid gland by stimulating tsab .\non the contrary , ht is thought to be due to a tsh stimulation - blocking antibody ( tsbab ) which blocks the action of tsh hormone and subsequently brings damage and atrophy to the thyroid gland .\nalterations in the thyroid state related to the balance between the activities of tsab and tsbab .\nmoreover , approximately 15 - 20% of patients with gd have been reported to have spontaneous hypothyroidism resulting from the chronic ht .\npatients with gd who have achieved remission on anti - thyroid drugs may also experience ht or hashitoxicosis or intermittent transient hyperthyrodism .\nthey may have both ht and gd since antibodies associated with both diseases may be present . to distinguish from relapsed gd a wait and see approach is beneficial .\na definitive diagnosis can be made by fnac biopsy , that is , fine - needle aspiration .\nhashimoto 's disease , which occurs following gd may be due to extended immune response to endogenous thyroid antigens , i.e. thyroid peroxidase and thyroglobulin , which may enhance lymphocyte infiltration and finally cause ht . in conclusion , ht rarely occurs following gd . in our case of an elderly lady ,\nabsence of eye signs , lobular - firm tender goiter with patchy uptake in both lower poles on tc99 m scan were odd points in diagnosing isolated gd .", "answer": "introduction : simultaneous occurrence of hashimoto 's thyroiditis ( ht ) , and graves disease ( gd ) is rare.aims and objectives : we report a case of simultaneous occurrence of gd and hd , at presentation.case report : a 60-year - old lady presented with tremulousness of hands , palpitation , and excessive sweating . \n she had a history of weight loss and neck - swelling . \n her weight was 46 kg , bmi 17 , afebrile , regular pulse rate of 110/min with fine tremor in hands . \n thyroid gland was symmetrically enlarged , firm , without any bruit , but mildly tender with lobular surface . \n there were no occular manifestations . \n initial thyroid function tests ( tft ) revealed : t3 : 3.80 ng / ml ( 0.80 - 2.10 ) , t4 : 12.40 ug / dl ( 5.10 - 12 ) , thyroid stimulating hormone ( tsh ) : 0.20 u / l ( 0.70 - 5 ) . her anti thyroperoxidase ( tpo ) antibody : 374 iu / ml ( normal [ nl . ] \n < 35 ) and tsh receptor antibody : 15 u / l ( nl . \n < 1 ) were both strongly positive . \n ultrasonogram of thyroid revealed a hypoechoic enlarged gland . \n 99mtc pertechnetate scan showed an enlarged gland with increased uptake of radiocontrast : 17% ( nl . \n 0.4 - 4% ) with some patchy defects in both lower poles . \n thyroid fine needle aspiration cytology ( fnac ) showed sheets of hurthle cells with abdunce of lymphocytes indicating ht . \n she was observed on beta blockers . \n repeat tft , 3 months later showed : t3 : 4.20 ng / ml , t4 : 14.40 ug / dl , tsh : 0.001 u / l , with increased uptake on repeat scan.conclusion:ht rarely occurs following gd . \n our case of an elderly lady with no eye signs , lobular , firm tender goiter with patchy uptake in both lower poles on tc99 m scan were odd points in diagnosing isolated gd . \n fnac confirmed simultaneous hd with gd .", "id": 920} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 52-year - old female patient visited the hospital complaining of pain in both breasts .\nthe pain started immediately after breast reduction surgery she underwent 3 years previously at a private plastic surgery hospital , and it had continued despite a subsequent surgery .\nthe pattern of the pain included burning , shooting and itching sensations at the operation site as well as unbearable burning sensations when the patient was in the places where the temperature was higher than normal .\nthe pain as measured by the visual analogue scale ( vas ) was approximately 70/100 mm .\nin particular , the degree of pain was dependent on the season , and it was unbearable under hot weather , with the patient complaining of pain at vas 80 - 90/100 mm . before coming to the hospital , the patient had taken aceclofenac ( airtal , daewoong pharmaceutical ) 200 mg , pregabalin ( lyrica , pfizer ) 300 mg , acetaminophen 1,300 mg and tramadol hcl 150 mg ( ultracet , janssen korea ) per day , but the pain was not relieved .\nthus , the patient tried pregabalin 600 mg , acetaminophen 1,300 mg and tramadol hcl 150 mg per day , but there was no effect .\ncomplaining of dizziness due to ultracet , the patient started to take 20 mg of oxycodone hcl ( oxycontin , mundipharma korea ) each day , but she eventually stopped taking it because of dizziness , nausea , and vomiting .\nsubsequently , the patient underwent drug treatment with pregabalin 300 mg a day , but she visited the hospital because the pain did not subside .\nthere was no specific finding in a simple plane chest x - ray spectrograph , while digital infrared thermographic imaging ( diti ) showed a slight temperature drop in both breasts .\nbecause the previous treatments were not effective in improving the symptoms and because the patient wanted another method of treatment due to the continued pain , it was decided that a thoracic epidural block would be performed , and informed consent was obtained from the patient .\nthe patient was laid on her side and the epidural space was checked using the loss - of - resistance method with a 22-gauge epidural needle ( hakko , japan ) in between the t4 and t5 , applying an aseptic technique in the interlaminar approach .\n0.5% mepivacaine hcl ( emcaine 2% inj. reyon pharm ) 6 ml was then injected .\nthe pain was relieved into the vas range of 40 - 50/100 mm after the procedure , and the patient was discharged .\nthe vas was decreased to 40 - 50/100 mm after an additional procedure a week later , but the patient complained of continued pain .\na decision was made to carry out prf to the spinal nerve and its root and . to measure the level and determine the effect\n, informed consent was received from the patient after she was provided with an explanation of the procedure and the side effects that may occur after the procedure . for the diagnosis ,\nselective nerve root block ( snb ) was performed at t3 , t4 and t5 , one level each time in order with an interval of 2 days , by injecting 1% lidocaine 0.5 ml with a 25-gauge quincke needle ( spinocan , bbraun ) .\nprf was carried out at the fourth thoracic spinal nerve and its root after giving an explanation to the patient about the procedure and the side effects that may occur after the procedure and receiving informed consent once again . after supporting the patient 's lower abdomen with a pillow and placing her in a prone position ,\nthe site of the procedure was disinfected by a common sterilizing method and a standard monitor was attached .\nthe area between t4 and t5 was identified in the anteroposterior view using a c - arm device and the 4 cm point right lateral from the t4 spinous process was chosen as the needle implantation point .\nlocal anesthesia was carried out with 1% lidocaine , and a 20-gauge 10 cm long rf cannula ( owl sharp curved rf insulated cannula , diros technology inc . ,\nusa ) with a 10 mm - active tip was then introduced into the anesthetized part . by continuously monitoring the position of the cannula with the c - arm\n, it continued to the inferior of end plate of fourth thoracic vertebral body ( fig .\n1 ) , and the tip of the cannula was located at the posterior border of the vertebral space in the lateral view ( fig .\n3 ) , and an rf generator ( rfg-3c plus , radionics , usa ) was then connected and an electric stimulus of 50 hz at 0.1 volt was applied .\nelectric stimulus of 2 hz at 0.1 volt was applied , and it was verified that the muscle did not contract up to 0.8 volt .\none minute after injecting 1% mepivacaine 1 ml , prf was performed two times for 120 seconds at 42. the same procedure was performed on the opposite side after one week . during the procedure , the vital signs of the patient were normal and no side effect took place . after the procedure , the pain was reduced to vas 20 - 30/100 mm .\nthe patient currently undergoes oral administration of pregabalin 300 mg / day and nortriptyline ( sensival , ilsung pharm ) 10 mg / day and this was followed up at the hospital for 9 months without particular exacerbation of the pain or any other inconvenience in her daily tasks .\npain after breast surgery , which is commonly complaint by patients , is known to be related with the injury , ischemia and inflammation of the soft tissue .\nif the pain in the affected part and arm continues for one year after the surgery , it is considered as chronic pain in general .\nthe mechanism is not yet accurately known , but the chronic pain may be caused by injuries in various peripheral nerves that arise during the surgery and can develop into neuropathic pain such as stabbing , pricking , burning , shooting and sharp pains .\nwallace et al . investigated 282 women who underwent different types of breast surgery , and their result showed that 31% of women who underwent mastectomy , 49% of those who underwent mastectomy with reconstruction , 38% of those who underwent cosmetic augmentation and 22% of those who underwent breast reduction complained of pain up to one year after the surgery .\nparticularly , as the survival rate of breast cancer patients has increased , the number of patients who complain of chronic pain after breast cancer survey has also increased .\nthe patient in this case study was also a chronic neuropathic pain patient whose pain had continued for 3 years following breast reduction surgery .\nshe complained of pricking , shooting and burning sensations at the site of the operation .\nalthough the patient complained of pain immediately after the surgery , she continued to suffer neuropathic pain for 3 years without being given appropriate pain treatment because she was not able to take medicine due to the side effects of the drugs .\nmacrae stated that severe acute pain after the surgery may be a risk factor for chronic pain .\nthis can be one possible cause of the chronic pain of the patient in this case report , because she complained severe pain at vas 70 - 80/100 mm immediately after the surgery but the pain was not properly controlled .\nin general , it is thought that the intercostal nerve ( icn ) from t1 to t6 and the nerves that originate from those braches can be damaged by breast surgery . for the patient in this case report , because she complained of the pain at the dermatome of the t4 spinal nerve , neuropathic pain caused by damage at the 4th icn and at the branch was suspected .\nthe effect of a nerve block in controlling pain after breast surgery is well known . in particular , it was reported that a paravertebral block ( pvb ) reduced pain , nausea and vomiting after breast surgery .\nin addition , kairaluoma et al . reported that preoperative pvb reduced chronic pain after breast surgery .\nthese results show that a nerve block can be used in controlling pain following breast surgery effectively , preventing it from becoming chronic .\na nerve block using a local anesthetic is easy to perform in the treatment of pain and is effective in reducing pain .\nhowever , because the duration of desensibilization may not be sufficient depending on the disease causing the pain and because many repeated procedures may be required , radiofrequency thermocoagulation is sometimes employed to maintain the effect of the nerve block .\nradiofrequency thermocoagulation was first introduced in 1930 's by kirschner , who applied it treating trigeminal neuralgia at the gasserian ganglion .\nrecently , the application of radiofrequency thermocoagulation in the case of various diseases has gradually increased as quality of the radiofrequency generator , the associated equipment , and the catheter needle has been improved .\nthis treatment is highly advantageous , in that a more accurate lesion can be generated compared to other nerve - destructive procedures . moreover ,\nthe mechanism of radiofrequency thermocoagulation is known to change the nerve tissue due to the heat around the electrode , blocking and the inflow of the nerve stimulus . on the other hand ,\nprf was introduced as a new method because another mechanism of radiofrequency - aided treatment arises in that a clinical effect is noted by the heat applied to the nerve and the electromagnetic field that forms around the electrode .\nprf is a radiofrequency - aided treatment in which pulsed radiofrequency stimulus of 20 msec is generated two times every 0.5 second at a temperature of 42 , which is low enough for the nerve tissue to remain undamaged .\nprf is a novel treatment method that has corrected the problems of previous radiofrequency - aided treatments based on heat .\nit does not cause nerve destruction , side effects such as neuritis , or the complications of other types of radiofrequency - aided treatments based on heat .\nit can be performed to treat neuropathic pain even for body parts where side effects take place frequently due to radiofrequency thermocoagulation .\nit can be also performed on parts near bone or scar tissue , where the risk of complications is high when radiofrequency thermocoagulation is performed .\nrohof applied prf to the suprascapular nerve in the treatment of chronic shoulder pain and reported it to be a novel treatment method that is free from side effects or complications , in contrast to the conventional thermocoagulation .\nmoreover , positive effects were reported when prf was applied to peripheral nerves such as the facial nerve , superior laryngeal nerve , suprascapular nerve , intercostals nerve , obturator nerve and the joint - dominating peripheral nerve articular branch , whose main nerve is sensory . in this case report as well , although the pain was controlled by an epidural block with a local anesthetic , repeated procedures were required due to the short duration of the first treatment .\nlong - lasting pain reduction was achieved without any specific side effect , as the prf was carried out on the spinal nerve and its root under monitoring by a c - arm device . in this article\n, we report a case in which prf was applied to control the pain of a patient who came to the hospital complaining of chronic severe neuropathic pain at the operation site that arose after breast reduction surgery .\nappropriate pain control after breast surgery can reduce the suffering of the patient due to early pain and greatly affect the quality of life of the patient by preventing the pain from being chronic .\nif an appropriate pain treatment had been given after breast surgery to the patient in this case report , she would have not suffered from chronic pain . in the case of breast surgery , considerable attention should be paid to postoperative pain as well as surgical pain , and pain treatment should be carried out positively .\nit is thought that a nerve block as well as general analgesics can be helpful as a pain control strategy .\nin addition , prf may be helpful in reducing the pain of the patients who are not responsive to a nerve block using analgesics or local anesthetics .\nfurthermore , additional studies are needed regarding the reduction of chronic neuropathic pain by prf after breast surgery .", "answer": "breast surgery is a common procedure performed in women . \n many women who undergo breast surgery suffer from ill - defined pain syndromes . \n a nerve block is used in the treatment of the acute and chronic pain , but the effectiveness of the treatment has been limited because of its short duration . \n recently , the advent of pulsed radiofrequency lesioning ( prf ) has proved a successful treatment for chronic refractory pain involving the peripheral nerves . \n we experienced a case of a 52-year - old female patient complaining of chronic breast neuropathic pain after breast reduction , which was relieved after prf lesioning of the 4th thoracic spinal nerve and its root .", "id": 921} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nudp - glcua ( ammonium salt ; > 98% purity ) , and nad ( sodium salt ; 98% purity ) were obtained from sigma aldrich .\npurified preparations of wild - type hugdh and e161q mutant were obtained using reported procedures .\nboth enzymes were produced as fusion proteins containing an n - terminal extension , which comprised a solubility enhancement tag , a streptavidin tag , and a tobacco etch virus protease cleavage site .\nthe n - terminal extension was then removed , and the enzymes were further purified by gel filtration and anion - exchange chromatography .\na 50 mm potassium phosphate buffer at pd 5.9 , 7.0 , 7.9 or 8.8 was used .\nstarting concentrations were 15 mm nad , 2 mm udp - glc and 0.38 m wild - type hugdh or 15 m e161q .\nafter addition of all components , the reactions were incubated at 25 c for 16 h. for determination of the solvent isotope effect , enzymatic conversions in h2o or d2o were performed in a beckman coulter du800 spectrophotometer using a 50 mm potassium phosphate buffer with ph / pd 7.5 .\nreaction velocity was measured by nadh absorption ( = 340 nm ) .\nall spectra were recorded on a bruker drx-600 avance spectrometer ( bruker , rheinstetten , germany ) at 600.13 mhz ( h ) .\nthe h nmr spectra were measured at 298.2 k with presaturation ( 1.0 s ) and acquisition of 32k data points .\nafter zero filling to 64k data points , spectra were performed with a range of 7200 hz .\nchemical shifts were referenced to external acetone ( h = 2.225 ppm ) .\nthe reactions were directly made in a 5 mm high precision nmr sample tube ( promochem , wesel , germany ) to measure in situ h nmr spectra .\nsamples contained 2 mm udp - glc , 15 mm nad , and 0.084 m wild - type hugdh or 33 m e161q , as well as 50 mm potassium phosphate buffer in d2o ( 0.70 ml , 99.9% d , pd 7.5 or 8.3 ) .\n12 h in the magnet by recording up to 64 h nmr spectra in regular intervals .\nthe topspin 3.0 software from bruker was used for processing the nmr spectra after data acquisition . for quantitative analysis of the nmr data ,\na correction value was subtracted from the integral values of each proton to account for background noise .\nudp - glcua ( ammonium salt ; > 98% purity ) , and nad ( sodium salt ; 98% purity ) were obtained from sigma aldrich .\npurified preparations of wild - type hugdh and e161q mutant were obtained using reported procedures .\nboth enzymes were produced as fusion proteins containing an n - terminal extension , which comprised a solubility enhancement tag , a streptavidin tag , and a tobacco etch virus protease cleavage site .\nthe n - terminal extension was then removed , and the enzymes were further purified by gel filtration and anion - exchange chromatography . full details of the purification protocol are given elsewhere .\nenzymatic assays were performed in 1 ml of d2o . a 50 mm potassium phosphate buffer at pd 5.9 , 7.0 , 7.9 or 8.8 was used .\nstarting concentrations were 15 mm nad , 2 mm udp - glc and 0.38 m wild - type hugdh or 15 m e161q .\nafter addition of all components , the reactions were incubated at 25 c for 16 h. for determination of the solvent isotope effect , enzymatic conversions in h2o or d2o were performed in a beckman coulter du800 spectrophotometer using a 50 mm potassium phosphate buffer with ph / pd 7.5 .\nreaction velocity was measured by nadh absorption ( = 340 nm ) .\nall spectra were recorded on a bruker drx-600 avance spectrometer ( bruker , rheinstetten , germany ) at 600.13 mhz ( h ) .\nthe h nmr spectra were measured at 298.2 k with presaturation ( 1.0 s ) and acquisition of 32k data points . after zero filling to 64k data points ,\nchemical shifts were referenced to external acetone ( h = 2.225 ppm ) .\nthe reactions were directly made in a 5 mm high precision nmr sample tube ( promochem , wesel , germany ) to measure in situ h nmr spectra .\nsamples contained 2 mm udp - glc , 15 mm nad , and 0.084 m wild - type hugdh or 33 m e161q , as well as 50 mm potassium phosphate buffer in d2o ( 0.70 ml , 99.9% d , pd 7.5 or 8.3 ) .\n12 h in the magnet by recording up to 64 h nmr spectra in regular intervals .\nthe topspin 3.0 software from bruker was used for processing the nmr spectra after data acquisition . for quantitative analysis of the nmr data ,\na correction value was subtracted from the integral values of each proton to account for background noise .", "answer": "graphical abstract", "id": 922} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe main goal of endodontic treatment is the complete apical and coronal seal of root canal system to prevent the bacterial leakage and percolation many studies have confirmed the importance of coronal leakage as a possible cause of failure of root canal treatment ( rct ) .\nmalone and donelly considered coronal restoration as it replaces missing tooth structure , protects remaining tooth from fracture , and prevents canals recontamination as the first protective barrier for the periapical tissues after rct .\ntorabinejad et al . , confirmed the results of swanson and madison 1978 that root canal treatment failure could be assumed to the delayed final restoration placement or when the temporary filling partially or completely lost .\nhence , a great attention should be paid for the immediate placement of coronal restoration .\nsome studies suggested the placement of a barrier made of different materials on the root canal orifices for complete coronal seal .\nthis barrier is indicated even in cases with post retained restorations . in 1995 , ray & trope published a radiographic study about the correlation between the periapical pathosis and endodontically treated teeth .\ntheir results indicated that the adequacy of the coronal restoration is more important than the quality of the root canal filling .\nthey also showed that the periapical pathosis related clearly to the quality of coronal restoration and not to the root canal filling .\nkirkevang et al . gained similar results . on the contrary , many studies , showed the adequacy of root canal filling is the most important preventive measure for the periapical tissues ( although there was no negligence on the coronal restoration importance ) .\nmoreover , ricucci and bergenholtz reported that exposure of root canal fillings to the saliva ( teeth with missing coronal restorations ) was not necessarily associated with apical pathosis in cases with adequate endodontic treatment .\nmany epidemiological studies from different countries : brazil , france , turkey , belgium and australia gave conflicting results about the impact of the final coronal restoration on the status of periapical tissues .\n2012 made a comprehensive review to studies related to this subject and could nt resolve this controversy .\nthe aim of this study was to assess the influence of the quality of coronal restorations and root canal treatment ( separately and in concomitant ) on the periapical status of endodontically treated teeth from an adult syrian subpopulation .\nwe randomly selected panoramic x - rays for patients attended dental school of damascus university who fulfill the selection criteria : patient 's age was set to be minimum of 19 years old , they had neither received any dental treatment for more than one year , nor had previously visited dental school clinics ( selected patients are private clinic patients ) .\nour sample contained 200 high qualities panoramic x - rays which had been examined under good illumination and magnification by two endodontists with minimum 5 years experience individually . in cases when disagreement occurred ,\nthe number of examines teeth in panoramic x - rays ( except third molars ) were 5331 teeth , 784 teeth ( 361 teeth for males and 423 teeth for females ) received endodontic treatments ( there was a radioopaque material in the root canals or pulp chambers ) .\nwe recorded the type of the final fillings as following : type of coronal restoration \n no filling in 39 teeth ( 5%)filling in 320 teeth ( 42.1%)prefabricated post & filling in 26 teeth ( 3.3%)crown in 304 teeth ( 38.8%)post & crown in 85 teeth ( 10.8% ) . \n no filling in 39 teeth ( 5% ) filling in 320 teeth ( 42.1% ) prefabricated post & filling in 26 teeth ( 3.3% ) crown in 304 teeth ( 38.8% ) post & crown in 85 teeth ( 10.8% ) .\nthe quality of the final restorations and root canal fillings had been classified as : adequate or inadequate according to tronstad et al .\ninadequate coronal restoration : final restoration appears radiographically with overhang , open margin , recurrent caries , temporary filling or no filling .\nadequate root canal filling : all canals obturated with dense fillings ending about 2 mm shorter than the radiographic apex .\ninadequate root canal filling : root canal fillings end more than 2 mm shorter than the radiographic apex or grossly overfilled .\nperiapical status was assessed by periapical index ( pai ) proposed by rstavik et al .\n1986 , who scored the periapical area of the radiographic images as follows : \n normal periapical structures.small changes in bone structure.changes in the bone structure with little mineral loss.periodontitis with well - defined radiolucent area.severe periodontitis with exacerbating features . \n normal periapical structures .\naccording to this index we classified periapical tissue as : normal or healthy periapex : absence of radiographic evidence of diseased periapical tissues .\nthe worst score of all canals was taken to represent the pai score for multicanal teeth .\nspss software was used for statistical analysis ( spss inc , chicago , il ) .\nout of 784 endodontically treated teeth , the mandibular molars were the most frequent treated teeth .\n459 cases ( 58.54% ) had been classified as having adequate coronal restoration , and 325 ( 41.46% ) cases as having inadequate one [ table 1 ] .\nillustrate the type of the teeth in the study and the adequacy of the final coronal restoration in the 459 teeth with adequate final restoration , the status of periapical tissues was healthy in 353 teeth ( 76.9% ) and diseased in 106 teeth ( 23.1% ) . in the 325 teeth with inadequate coronal restoration , the status of periapical tissues was healthy in 169 teeth ( 52% ) and diseased in 156 teeth ( 48% ) [ table 2 ] .\nillustrate the status of periapical tissues according to the adequacy of final coronal restoration chi - squared test was used to evaluate the major differences in the status of periapical tissues according to the adequacy of final coronal restoration as illustrated in table 3 .\nevaluation of the major differences between studied groups statistical analysis revealed that the healthiness of periapical tissues affected by quality of coronal p < 0.01 [ table 4 ] .\nthe effect of coronal restoration type on the status of periapical tissues the study showed that 72% of the cases with final restoration absence accompanied with a clear radiographic radiolucency .\nteeth with prefabricated post and filling or cast post and crown accompanied with periapical pathosis ( 38.5% and 31.8% ) respectively .\noverall , the post presented in 111 cases ( 14.1% ) , 74 cases accompanied with healthy periapical tissues and 37 cases with diseased tissues .\nendodontic treatments had been evaluated as adequate in 145 teeth ( 18.5% ) , and inadequate in 639 teeth ( 81.5% ) . when we compared the status of periapical tissues according to the adequacy of root canals fillings we noticed that 95.2% of the teeth were with adequate root canal fillings , and about 60.1% of the inadequate endodontically treated teeth were with healthy periapical tissues ( score one and two rstavik et al .\nperiradicualr disease ( pai > 2 ) had been found in 262 teeth ( 33.4% ) . 7 cases of there were with adequate treatment and 255 cases were inadequate [ table 5 ] .\nthe status of periapical tissues according to the adequacy of the root canal filling the difference in the number of teeth with healthy periapical tissues and adequate root canal filling were significant when compared to teeth with inadequate root canal filling .\n( p < 0.001 ) . the impact of the adequacy of the coronal restoration and root canal filling on the status of periapical tissues had been studied ( separately and in concomitant ) .\nclassification of teeth according to the adequacy of the final restoration and root canal filling in this study the status of periapical tissue were healthy in 96.6% of cases when both final coronal restoration and root canal filling were adequate .\nbut the status of periapical tissues was healthy in 88.5% when only the root canal fillings were adequate and 70% when only the coronal restoration was adequate .\nthe status of periapical tissue was healthy in only 48.8% of cases when both the endodontic treatment and the final restoration were inadequate [ table 7 ] .\nthe effect of endodontic treatment and the final coronal restoration on the status of periapex for cases with both adequate restorations and adequate root canal filling , the success rate was 96.6% .\nhealthy periapex was observed in 88.5% of the teeth with adequate root canal filling and inadequate restoration .\nwhen only the final restoration was adequate ( root canal treatment inadequate ) the success rate was 70% ( p = 0.04 ) .\nthe difference when both the final restoration and the root canal filling were inadequate was significant when compared to the other three groups .\nthis epidemiological study used x - rays to evaluate the presence of periapical radiolucencies , the quality of the root canal fillings and restorations with all limits of the 2 dimensional images .\none of this study disadvantages is the inability to collect detailed information about the endodontic treatment : when it was done ? if the periapical pathosis is pre or post treatment disease ? whether the periapical periodontitis is healing or expanding ?\nin fact , radiographic image represents a snapshot of a continuous process of a dynamic disease . according to the study of petersson et al .\nthe number of healed lesions equals the number of developed ones after 10 years of follow up , indicating the reliability of epidemological studies for recording the long - term success of endodontic treatments .\nthis type of studies gave us valuable information about the level and development of dental practice in different periods , the common endodontic errors and the prevalence of periapical pathosis in subpopulations .\nto overcome the disadvantages of this type of studies , the sample was expanded and radiographs had been evaluated by using good illumination and magnification . all panoramic x - rays in this study were taken in dental school clinics of damascus university .\nmany studies did not find significant differences between periapical and panoramic x - rays in evaluation of periapical pathosis .\none of the most important questions is whether the study represents the syrian subpopulation ? to come up to an answer we should mention that dental school clinics of damascus university is one of the biggest dental clinics in damascus that offers consultations and treatments to so many people from damascus and its province\n. the criteria of sample selection was : the patient should have received his previous treatment outside dental school clinics ( by general practice dentists ) , did not receive any dental treatment for at least one year of attendance to give a chance for any radiographic radiolucency to be healed by that time . according to rstavik d ( 1996 ) 89% of lesions would heal after one year of endodontic therapy .\nthe number of endodontically treated teeth was 784 teeth ( half of them were upper and lower molars ) .\nthe prevalence of periapical lesions was about 33.42% , 58.5% of the coronal restorations were evaluated as adequate with different type of restorations , while 5% of the sample lost its restorations .\nthe incidence of apical periodontitis associated with adequate coronal restorations was lower with significant difference than inadequate ones .\nthe effect of the type of the coronal restorations on the status of periapical tissues was not crucial . in 111 cases out of 784 cases ,\nsome studies indicated that the presence of canal posts accompanied with higher percentage of periapical pathosis due to leakage during post space preparation or infrequent irrigation or weakening the remaining gutta percha .\nroot canal filling was adequate in 18.5% of cases which is so low when compared to other studies that consider root canal therapy as predictable treatment . in this study ,\nthe correlation between periapical pathosis and inadequate root canal treatment was highly significant , other studies confirmed these results . when each factor ( root canal filling or coronal restoration ) was evaluated separately , it had a significant influence on periapical health ; in fact , these two factors are un separated . to evaluate which factor\nhad the greater impact on outcome , we statistically analyzed the results of combination of these two factors .\nsuccess rate ( the presence of healthy periapex ) scored in 96.6% of cases with adequacy of both factors and decreased to 88.5% in cases with adequate root canal fillings and inadequate coronal restorations but with non - significant difference ( it means that root canal treatment exert greater impact on outcome ) . in cases with adequate coronal restorations and inadequate root canal fillings success rate\nwas recorded in 70% , which again indicates the importance of root canal filling in the success of the endodontic treatment .\nthe worst results were obtained when both factors are inadequate which accompanied with lower successful results and high significant difference compared to all studied groups .\nthat indicates the importance of a complete treatment ( adequate root canal filling and placement of adequate final coronal restoration ) .\noverall results indicate that the factor that plays the key role in the success of a treatment is the quality of root canal filling without neglecting the effect of the coronal restoration .\nthe prevalence of periapical lesion in syrian subpopulation is high which indicate poor dental practice .\nthus , considerable efforts should be spent to improve the level of endodontic treatment and promote periradicular health .", "answer": "background : the purpose of this study was to determine the status of periapical tissues of endodontically treated teeth according to coronal restorations and root canal fillings separately and in concomitant in adult syrian subpopulation.methods:784 endodontically treated teeth from two hundred randomly selected syrian adult patients were radiographically evaluated . according to predetermined criteria , the quality of coronal restorations and root canal filling of each tooth \n was scored as adequate or inadequate . \n the status of periapical tissues was also classified as healthy or diseased . \n results were analyzed using chi - squared test.results:adequate coronal restorations were determined in 58.54% of cases which was accompanied with less periapical pathosis than that in teeth with inadequate restorations ( p < 0.01 ) . \n 14% of teeth were restored by posts which showed no significant impact on the periapical tissues health . \n 18.5% of endodontic treatments were evaluated as adequate with less number of periapical radiolucencies than that of inadequate root canal fillings ( p < 0.01 ) . \n absence of periapical pathosis was 96.6% in cases with both adequate coronal restorations and root canals fillings . \n the rate was 88.5% in cases with only adequate root canals fillings , and about 70% in cases with only adequate coronal restorations . \n when the treatment was inadequate in both coronal and root canals fillings , success rate was only observed in 48.8%.conclusion : the most important factor with regard to the periradicular tissue health is the quality of root canal filling without neglecting the influence of coronal restoration ( regardless of its type ) . \n there is a high prevalence rate of periapical pathosis in syrian subpopulation due to poor dental practice .", "id": 923} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\naccording to numerous estimations , 15% to 29% of patients with cataract have 1.5 diopters ( d ) of refractive astigmatism.1,2 cataract surgeons usually prefer to treat cataract and correct refractive ( spherical and astigmatic ) disorders at the time of the surgery .\ncorneal incision ( astigmatic keratotomy ) and peripheral corneal relaxing incisions ( pcris ) were performed to treat these disorders.3,4 the main drawbacks of these approaches are that the outcome depends on multiple factors as the patient s age , the depth and length of the incision , complications related to wound healing , epithelial defects , or induction of dry - eye symptoms .\nthese parameters affect the visual outcome in a unpredictable way so the corneal incisions are not considered a reliable method for astigmatism correction .\ntoric intraocular lens ( iols ) implantation was introduced in the 1990 s as an option for astigmatism correction in cataract patients .\ninitially they presented the disadvantage of postoperative rotation that decreased the visual outcome.58 new toric iol designs ( acrysof toric iol ; alcon , fort worth , tx ) , approved by the us food and drug administration ( fda ) at the end of 2005 , have been found to be more stable and appear to be the preferred iol for correcting preexisting astigmatism in conjunction with cataract surgery.9,10 the acrysof iols are available in three options : t3 , t4 , and t5 of astigmatic correction 1.5 , 2.25 , 3.00 d , respectively ( at the iol plane ) .\nthe aim of this study is to report the clinical results of acrysof toric iols implantation for preexisting astigmatism correction and compare the postoperative rotation of the iols one and six months postoperatively .\nthis prospective study included eyes that had cataract surgery at the papageorgiou general hospital , thessaloniki , greece , between may 2008 and december 2008 .\nthe study was conducted according to the tenets of the declaration of helsinki and patients gave informed consent after the nature and intent of the study had been fully explained to them .\ninclusion criteria were : cataract , age 70 years or younger , and preoperative regular corneal astigmatism greater than 1.00 d. exclusion criteria were : glaucoma , corneal disease , previous corneal or intraocular surgery , macular degeneration or retinopathy , and history of ocular inflammation .\neach patient had a complete ophthalmologic examination , including visual acuity ( va ) , slit - lamp examination , intraocular pressure ( iop ) measurement , and dilated fundus examination .\ntopography ( magellan mapper ; nidek technologies , padova , italy ) , automated refractometry ( rk600 ; reichert , inc .\n, depew , ny ) , and ultrasonic immersion biometry ( ocuscan rxp ; alcon ) were performed to determine the appropriate iol spherical power .\ncylindrical power and axis placement to achieve emmetropia were calculated using an online toric iol calculator program ( available from http://www.acrysoforiccalculator.com/ ) .\nthe 0180 axis was marked with the patient in a sitting position to avoid cyclotorsion using the nuijts / lane preoperative toric reference corneal marker ( ae-2791tbl ; asico , westmont , il ) ( figure 1 ) .\nintraoperatively , the desired implantation axis was marked using an intra - op toric axis marker ii ( ae-2794 ; asico ) ( figure 2 ) .\na foldable iol was implanted in the capsular bag through a 2.75 mm limbal incision on 110. the toric iol was injected with a monarch - ii injector ( alcon ) and placed around 1015 off axis before the ophthalmic viscosurgical device ( sodium hyaluronate 1% ) was removed .\nafter ophthalmic viscosurgical device removal , the iol was rotated to its final position by exactly aligning the toric reference marks with the limbal implantation axis marks .\nall surgeries were performed by the same experienced surgeon ( it ) using topical anesthesia and a standard divide - and - conquer phacoemulsification technique . because of the intraoperative marker design and the pen mark fading during the operation in several cases , it was difficult to assess the proper alignment of the iol after its placement . because of this difficulty , an image was captured from the real - time streaming recording of the surgery and was assessed blindly by a second operator using a commercially available software ( screen protractor ; iconico , ny , usa ) ( unpublished data ) . to overcome this difficulty we consider that the use of the marker set consisting of beveled degree gauge ( ae-1590 ; asico ) and maloney astigmatism axis marker ( ae-2741 ; asico ) is more appropriate for the whole procedure because it allows maximum visibility .\nthe on - screen assessment of the axis remains a useful tool for postoperative evaluation of the iol location ( figure 3 ) .\nmeasurements of visual acuity ( using the snellen opto - type at a six - meter distance ) , iop , and comprehensive slit lamp examination were performed at one - day and one- and six - month postoperative visits . at the one- and six - month follow - up\n, a digital photograph and corneal topography ( only at the one - month visit ) were obtained to estimate the postoperative rotation of the iol using the software tools mentioned above ( figure 1 ) .\noutcomes of interest included uncorrected va , cylindrical astigmatism power before and after iol implantation , and the possible rotation of the iol one and six months after the operation ( when the initial desired place was at 0 ) .\nabsolute values of the rotation used for the analysis after detecting rotation was not under investigation .\ncompleted data forms were analyzed with microsoft excel 2007 ( microsoft corporation , redmond , wa ) and spss software ( version 16.0 ; spss inc . , chicago , il ) .\ntwenty - nine eyes of 19 patients ( mean age 63.03 5.42 years ) were enrolled in this study .\nuncorrected va was found to be 5/10 or more in 26 of 29 eyes ( 89.7% ) and 8/10 or more in 19 of 29 patients ( 65.5% ) .\npreoperative and postoperative corneal topography showed significant reduction of refractive astigmatism in all eyes after the surgery .\nmean power of the astigmatism was 2.38 0.91 d ( range 1.55 d ) preoperatively and 0.64 0.61 d ( range 02.5 d ) postoperatively ( figure 4 ) .\none month postoperation , the mean toric iol axis rotation was 2.2 1.5 ( range 0.67.8 ) .\nsix months postoperation , the mean toric iol axis rotation was 2.7 1.5 ( range 0.98.4 ) .\nthe later rotation occurred between one and six months , and was found to be more than one degree ( 1.1 ) only in one eye ( 3% ) and in all other cases was less than this value ( figure 5 ) .\nit is known that one degree of deviation causes 3.3% reduction of the iol cylindrical power .\ncalculated reduction of the desired correction ( in diopters ) because of the observed rotation ( mean value , one and two standard deviations ) for the three iol models is shown in table 1 .\nno eye had secondary surgery to reposition the iol axis within the six - month postoperative period .\nthe results of our study corroborate previous studies,11 which demonstrates that proper selection and preoperative examination of patients followed by uncomplicated iol implantation of one - piece hydrophobic acrylic toric iols results in acceptable stability and visual outcome .\nin particular , the postoperative rotation of toric iols appears to occur in the early postoperative period ( 1 month ) and remains constant later than six months .\nthe lens rotates until a fibronectin and collagen adhesion develops between the iol and the posterior capsule , which prevents any further rotary motion.12 the amount of cylindrical correction reduction due to postoperative rotation was not large enough13 to affect the expected end result in final uncorrected distance va .\nacrysof one - piece hydrophobic acrylic toric iols implantation shows satisfactory stability , acceptable clinical results , and is an exceptional option for correction of refractive astigmatism .", "answer": "purpose : to present clinical results of toric intraocular lens ( iol ) implantation for preexisting astigmatism correction and determine the time of any postoperative rotation.patients and methods : twenty - nine eyes of 19 patients underwent uncomplicated phacoemulsification and were implanted with an acrysof toric iol . uncorrected visual acuity , residual astigmatism , and postoperative rotation of the iol were estimated one and six months after the operation.results:uncorrected visual acuity was 0.5 in 26 of 29 eyes ( 89.7% ) and 0.8 in 19 of 29 patients ( 65.5% ) . \n the mean toric iol axis rotation was 2.2 1.5 ( range 0.67.8 ) one month postoperation and 2.7 1.5 ( range 0.98.4 ) six months postoperation.conclusion:implantation of one - piece hydrophobic acrylic toric iols appears to have acceptable stability , which encourages visual outcome and emerges as an attractive alternative for correction of refractive astigmatism .", "id": 924} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthere has been a striking upsurge in tuberculosis ( tb ) vaccine research in china in recent years .\nmore than 80 papers reporting such research have been published since 2004 ( figure 1 ) , many in english language journals .\nthis has been driven and funded largely by chinese government agencies , since the scale of the tb problem and the difficulties in implementing fully effective control measures were recognized .\n, we can note that there are at least two additional restricting factors limiting the progress of the field in china : few research groups have access to facilities for safely working with animals infected with a dangerous pathogenic organism such as the tubercle bacillus ; infrastructure for undertaking vaccine clinical trials to international standards is sparse . in consequence ,\nthe universal problem of how to select among the promising approaches and candidate vaccines is particularly acute in china .\nnevertheless , the basic research problems are being tackled with some enthusiasm and creativity , and the new 5-year program to improve tb control that was announced by the chinese ministry of health on 1 april 2009 will have an impact .\nthe antigens investigated to date and the locations of research groups are listed in tables 1 and 2 , respectively .\na substantial body of work has gone into characterizing the immune responses to be found in tb infection and following vaccination .\nthe twin purposes of identifying candidate antigens for use in vaccines and diagnostic tests and of defining immunological markers for latent infection and disease states drive these studies .\nthese studies have not always been followed up with tests of protective or therapeutic efficacy in animal infection models .\nthe increased immunogenicity of mouse dendritic cells transfected with antigen heat shock protein 65 ( hsp65 ) has been tested in wuhan and in hong kong , and differences have been found in the polarizing effect of intracellular mycobacterium bovis bacille calmette guerin ( bcg ) vaccine bacteria on antigen presentation by human adult and cord blood dendritic cells .\nvarious forms of recombinant bcg expressing early secreted antigen 6 of mycobacterium \n tuberculosis ( esat6 ) , or antigen 85b ( ag85b ) and antigen rv3425 , or ag85b and esat6 with tumor - necrosis factor- , or esat6 and human granulocyte macrophage - colony stimulating factor ( gm - csf ) have shown enhanced immunogenicity .\nrecombinant m. smegmatis expressing m. tuberculosis culture filtrate protein 10 ( cfp10)/esat6 fusion protein was found stimulatory for macrophage inducible nitric oxide synthetase .\nrecombinant m. smegmatis and bcg strains have been made that can express cloned antigens at a range of different levels under the control of modified fura gene promoters .\nother bcg recombinants expressing esat6 , esat6/interleukin 2 ( il-2 ) or ag85b / esat6 fusions have been made .\na range of known antigens has been tested for immunogenicity as mixtures , fusion proteins and peptides .\nthese include chimeric ag85b / esat6 with adjuvants monophosphoryl lipid a ( mpl ) and trehalose 6,6'-dimycolate , hsp16.3 with dimethyl - dioctadecyl - ammonium bromide / mpl ( dda / mpl ) adjuvant , fusion protein m. tuberculosis protein 64 ( mpt64)esat6 , resuscitation - promoting factor b ( rv1009 ) , or cfp10 , esat6 or rpfe ( rv2450 ) with nitrocellulose , or rv3772 and rv3425 with incomplete freund 's adjuvant ; or ag85b / mpt64190198/mtb8.4 plus a novel adjuvant of dda with bcg extract .\nin - silico analysis of putative mhc class 1-restricted epitopes present in antigens encoded within the region of difference 1 ( rd-1 ) to rd-16 regions of m. bovis genome has revealed potential high - affinity hla binders and profiles of human humoral responses to 38-kda , mtb48 , cfp10/esat6 antigens have been defined .\nscreening of human immune sera against an expression library of m. tuberculosis open reading frames revealed three novel antigens among the top 20 most strongly recognized : rv1987 , rv3807c and rv3887c .\nmore than a dozen studies have used dna vaccination as a means of delivering antigens in immunogenicity tests . many have shown th1-biased immunogenicity without additional adjuvanting , for example with ag85b , ag85b / esat6 fusion , esat6/cfp10 fusion , mtb8.4/38-kda / ag85b fusion and epitopes from esat6 , ag85a , cfp10 and ag85b inserted within hsp65 .\ntargeting the expressed product for degradation via the ubiquitin pathway has been used to enhance mhc class 1 presentation of epitopes from mpt64 and 38-kda , mpt64 , and esat6 .\nenhanced responses to encoded antigens have been obtained by additionally encoding cytokines , such as interleukin 21 ( il-21 ) , with ag85a or ag85a / esat6 , and gm - csf with ag85a .\ninclusion of dna expressing il-12 enhanced prime / boost responses to bcg and to plasmids expressing ag85a and esat6 .\nesat6 dna priming and protein boosting has also been shown to give enhanced th1 responses .\nmany antigen preparations have been tested for their capacity to protect against challenge infection with virulent m. tuberculosis .\nsubcutaneous esat6/cfp10 , or esat6/mpt64 fusion proteins on nitrocellulose protected mice against h37rv challenge , but not as effectively as bcg .\nhsp65/il-2 fusion protein was found to elicit better protection than hsp65 given with dda / mpl adjuvant and protection was equivalent to that produced by bcg .\nsimilarly , either hspx , a dormancy associated antigen , or synthetic epitope 91104 gave protection equivalent to bcg when given with dda / mpl .\n/ mpt64190198/mtb8.4 fusion protein with dda adjuvant boosted protection against challenge in bcg primed mice .\na similar fusion protein in which mtb8.4 was replaced by hspx gave a similar boost , but boosting with a mixture of the two fusion proteins was even better .\na fusion protein of esat6 and ag85a also significantly boosted protection against h37rv in mice .\nrecombinant bcg expressing the ag85b / mpt64190198/mtb8.4 fusion protein gave slightly better protection to mice against h37rv challenge than parent bcg or bcg expressing rag85b alone .\nrecombinant bcg expressing a fusion protein of human interleukin ( hil)-12p70 and esat6 showed increased immunogenicity but less protective effect .\nrecombinant salmonella typhimurium that both expressed esat6/ag85b fusion protein and delivered it as a dna vaccine when given orogastrically gave protection similar to subcutaneous bcg and the combination was superior to either vaccine alone .\nthe earliest reports indicated protection in mice superior to bcg when a divalent construct expressing both ag85b and mpt64 , or a mixture of plasmids expressing ag85b , mpt64 , mpt63 and esat6 was used . the protection given by a mixture of three plasmids expressing mpt83 , ag85b and esat6\nwas enhanced by including dda adjuvant and an encoded fusion protein of ag85b and mpt64 was superior to the separately encoded antigens .\nencapsulation in poly(lactide - co - glycolide ) microspheres with dda enhanced the protective efficacy in mice of dna - encoding ag85b / mpt64/mpt83 fusion antigen , and strikingly the dna mixed with dda was superior to bcg in protecting cattle against challenge .\ninclusion of a plasmid expressing il-2 improved protection by this plasmid or by plasmid expressing mtb8.4 .\na mixture of plasmids encoding ag85b , mpt64 , mpt70 and tb10.4 boosted protection by bcg , as did a plasmid expressing a cfp21/mpt64 fusion protein .\nag85b or ag85a were superior to esat6 when compared separately for protection as dna vaccines .\ndna expressing a fusion of mpb64/ag85b / esat6 was superior to a mixture of plasmids expressing the separate antigens and gave protection equivalent to bcg .\nthe protective effect of dna expressing hsp65 against bcg challenge was enhanced by incorporating epitopes of esat6 , ag85a / b and cfp10 within the hsp65 backbone .\nthe protective effect of hsp65 dna against h37rv challenge was increased by expression as a fusion with hil-2 , but did not surpass that of bcg .\nexpression of ag85b fused to bovine herpes virus 1 vp22 protein , which facilitates dissemination of antigen to adjacent cells , resulted in protection against h37rv challenge in mice that was better than protection by bcg .\nfew studies have been conducted with animals other than mice : a mixture of ag85b , hspx and cfp10/esat6 fusion together with cpg and aloh as adjuvant was immunogenic in mice but gave little protection against challenge with h37rv in guinea pigs ; in contrast , combined dna vaccines encoding antigens ag85b , mpt64 and mpt83 given with dda appeared to be better than bcg in protecting cattle .\ninterest in therapeutic vaccination has been sustained by clinical studies of a commercial chinese product , m. vaccae extract .\nrecent meta - analyses of published data concluded that this product gave significant benefit in preventing tb in people at high risk ( 13 studies ) , but there was only a minor benefit from treating new tb cases ( 54 studies ) . in a unique and contrasting approach\n, a recombinant m. smegmatis delivering dna expressing human granulysin and murine il-12 was recently found to be therapeutic against h37rv infection .\nmost research into therapeutic vaccines for tb has focused on the use of naked dna vaccination .\ndna had a significant therapeutic effect against h37rv in mice and the fusion hsp65/il-2 was significantly better .\ntreatment of infected mice with a dna vaccine expressing a fusion protein of mycobacterial hsp70 and leukocyte cluster of differentiation antigen 80 substantially reduced acid - fast bacteria and pathology in liver and spleen , whereas bcg had no effect .\nalthough treatment with dna expressing ag85b was therapeutic , treatment with dna expressing mpt64 was not , and the mixture was less effective than the ag85b vaccine on its own , and inclusion of dna expressing il-12 gave a slight additional benefit .\nmice infected with a clinical isolate resistant to isoniazid and rifampicin responded well to treatment with the drugs plus dna expressing chimeric ag85a / esat6 , and appeared to respond better to treatment with the drugs plus dna expressing ag85a than to the dna vaccine alone ; ag85a dna alone was at least as effective as ag85a plus rifampicin in treating mice infected with a strain resistant to rifampicin and isoniazid , ag85a\nan immunogenic mixture of dna vaccines expressing ag85b , mpt64 and mpt83 has been found to work as a potent adjunct to isoniazid plus pyrazinamide therapy in mice and to be therapeutic in cattle infected with m. bovis , reducing both pathology and bacterial numbers ; a mixture expressing ag85b , mpt64 and hsp65 was similarly effective .\ninclusion of immunostimulatory nucleotide motifs in the gene transcript enhanced the therapeutic efficacy of a plasmid expressing hsp65 when tested against h37rv in mice .\nit is evident in considering this body of recent tb vaccine research in china that much of it has been tactical in nature , establishing credentials both nationally and internationally , and building new research bases . additionally , there are creative and insightful studies of particular relevance to the needs of china .\nresearchers are now able to exploit cutting edge technologies in designing new tb vaccines and are increasingly able to test the vaccines in relevant animal models of infection .\nthe evidence that dna vaccines can provide effective therapy for tb in cattle may be a significant pointer to the future .\nthe potential benefits of adding immunotherapies / therapeutic vaccines to tb chemotherapy have been recognized in china , but both preventive and therapeutic approaches against human tb await development of clinical trial capacity for their proper assessment .", "answer": "it is now privately acknowledged that there may be little if any perceptible impact of the national bacille calmette guerin ( bcg ) vaccination program on disease prevalence , despite the extensive coverage of the newborn infant population and likely benefit in the early years of life . a better preventive vaccine than bcg is now being sought by chinese researchers . \n urgency has been added to the control problem by the emergence of multidrug - resistant tuberculosis ( tb ) . \n furthermore , expensive second - line drugs seem unlikely to be made available by the government to treat drug - resistant cases , so attention in addition has turned to the potential of immunotherapy as an adjunct to chemotherapy . \n research trends are summarized here .", "id": 925} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfrom the first reported infected patient in may 2009 through january 2010 , a total of 740,835 patients in south korea were reported as having pandemic ( h1n1 ) 2009 virus infection .\na total of 225 patients ( 0.03% ) died of disease related to pandemic ( h1n1 ) 2009 . during this period ,\nphysicians in local clinics and tertiary hospitals sent specimens from 67 patients who were suspected of having drug - resistant pandemic ( h1n1 ) 2009 to the korea centers for disease control ; 11 patients ( 16% ) had drug - resistant virus ( figure ) .\nafter confirmation of drug resistance , epidemic intelligence service officers obtained clinical and epidemiologic data by medical record review and interviews with household contacts and attending physicians for all patients .\nclinical course and outcome of 11 patients with oseltamivir - resistant pandemic ( h1n1 ) 2009 , south korea .\nsymptom aggravation was defined as influenza - related symptoms that worsened regardless of new infiltrations seen by chest radiography .\nsymptom improvement was defined as influenza - related symptoms ( nasal stiffness , sore throat , cough , myalgia , fatigue , headache , and fever ) that were absent or mild .\ned , emergency department . to investigate whether virus contained genetic markers associated with resistance to antiviral drugs , a conventional genotyping assay ( sequencing ) was performed , and neuraminidase ( na ) and matrix 2 genes were sequenced .\nall 11 patients had virus with a histidine - to - tyrosine mutation at residue 275 of the na protein ( h275y ) ; 1 patient also had virus with an i117 m mutation ( figure ) .\ndetailed molecular epidemiologic data and genetic characteristics of the isolates are described elsewhere ( 2 ) . of the 11 patients ,\n6 were < 59 months of age and 5 had underlying immunosuppressive conditions ; only 1 patient was immunocompetent and > 59 months of age ( table ) . three patients from whom samples before and after treatment with oseltamivir were available showed evidence of having acquired the h275y mutation during oseltamivir therapy .\nnone of the 11 patients received oseltamivir chemoprophylaxis . * specimens were obtained from oropharyngeal ( n = 7 ) and nasopharyngeal ( n = 2 ) swabs , nasopharyngeal washings ( n = 1 ) , and brochoalveolar lavage fluid ( n = 1 ) . \npatients who had underlying diseases such as hiv infection , malignancy , liver cirrhosis , or chronic renal failure , or patients receiving immunosuppressive treatment . \n carbapenem - resistant pseudomonas aeruginosa ( patient 3 ) , carbapenem - resistant acinetobacter \n baumanii ( patient 4 ) , and penicillin - susceptible streptococcus pneumonia ( patient 10 ) . of the 3 patients , 1 was infected with carbapenem - resistant p. aeruginosa ( patient 3 ) and 1 was infected with carbapenem - resistant a. baumanii ( patient 4 ) .\nwe also tested 100 persons who had contact with the 11 patients for possible transmission of drug resistance .\neight of 100 were confirmed as having been infected with pandemic ( h1n1 ) 2009 virus before the 11 patients were infected .\ninfluenza - like illnesses developed in the 11 patients a median of 2 days ( range 17 days ) after the 8 contact persons were confirmed as having pandemic ( h1n1 ) 2009 .\nfive of the 8 contact patients were children ; none had an immunosuppressive condition or were given oseltamivir chemoprophylaxis before illness ; and 7 of 8 were < 59 months of age .\noseltamivir - resistance tests were not performed for these 8 patients because they all received oseltamivir therapy and their clinical symptoms resolved .\ntherefore , the possibility of transmitted resistance from contact patients was not demonstrated in this study .\nall 11 patients were initially given the usual dose of oseltamivir ( 75 mg 2/day in adults ) .\nafter detection of oseltamivir resistance , treatment regimens were as follows : 3 patients were given high - dose oseltamivir ( 150 mg 2/day in adults ) , 3 patients were given combination therapy ( oseltamivir and amantadine ; oseltamivir and peramivir ; and oseltamivir , amantadine , and ribavirin , respectively ) ; 3 patients were given zanamivir nasally ; and 2 patients continued to receive oseltamivir .\nseven of the 11 patients had complications during treatment : 6 had viral or secondary bacterial pneumonia and 1 had acute respiratory distress syndrome ( table ) .\npatient 3 died 15 days after confirmation of infection with pandemic ( h1n1 ) 2009 virus and 10 days after the emergence of oseltamivir - resistant virus .\npatient 4 died 15 days after confirmation of infection and 4 days after emergence of oseltamivir - resistant virus .\npatient 8 , who was infected with virus that had h275y and i117 m mutations , died 18 days after confirmation of infection and 4 days after the emergence of oseltamivir - resistant virus .\nour nationwide surveillance of drug - resistant pandemic ( h1n1 ) 2009 in south korea indicated that most patients were children ( < 59 months of age ) or immunocompromised .\nall isolates had the h275y mutation in the na protein , and 1 isolate also had the i117 m mutation in the same protein .\nour finding that oseltamivir resistance developed in immunocompromised patients is consistent with those of recent case reports that described development of oseltamivir resistance in immunosuppressed patients receiving this drug ( 3,4 ) .\na recent study in australia reported that 4 of 32 adult oncology and hematology patients were infected with oseltamivir - resistant virus with the h275y mutation ( 5 ) . in 3 of our patients ( patients 3 , 5 , and 11 ) drug - resistant\nthus , we suggest that physicians be alert to emergence of oseltamivir - resistant pandemic ( h1n1 ) 2009 , particularly if there is treatment failure with oseltamivir or prolonged viral shedding is evident . more than half of our patients were < 59 months of age , indicating that a younger age may be a risk factor for infection with drug - resistant pandemic ( h1n1 ) 2009 .\nclinical trials have reported oseltamivir resistance in < 5.5% of children with seasonal influenza ( 6 ) .\nexplanations for the higher rate of drug resistance in children than in adults are that children have a more protracted course of influenza , longer viral shedding times , and higher viral titers ( 7 ) .\nanother explanation might be that we can not rule out suboptimal dosing of oseltmaivir in children , although world health organization dose standards were used ( 8) and all pharmacies were given instructions on emergency compounding of oseltmaivir .\navailability of pretreatment and posttreatment samples indicated that resistance to oseltamivir developed during treatment in > 3 patients .\none case report ( 9 ) , 1 report of a cluster of cases in vietnam ( 10 ) , and 1 outbreak in a hematologic ward ( 11 ) documented patient - to - patient transmission of oseltamivir - resistant virus .\none of our patients was infected with virus that had a novel na mutation ( i117 m ) .\na previous study indicated that the i117v mutation in avian influenza virus ( h5n1 ) was associated with low - level oseltamivir resistance ( 12 ) .\nthe i117 m mutation of na may contribute to oseltamivir resistance , but it is not clear whether isolates with these 2 na mutations have higher levels of resistance or virulence than the h275y na mutant .\nwe found few patients with drug - resistant pandemic ( h1n1 ) 2009 in south korea .\nhowever , our study was based on the nationwide surveillance system for drug resistance among patients with suspected oseltamivir treatment failures , which is different from other surveillance systems , in which all isolated viruses are tested .\nthus , we can not report the prevalence of drug - resistant pandemic ( h1n1 ) 2009 and risk factors for drug - resistant virus infection in south korea .\nfurther studies are needed to monitor oseltamivir resistance , especially in immunosuppressed or pediatric patients when treatment failure with oseltamivir or prolonged viral shedding occur .", "answer": "eleven patients with drug - resistant pandemic ( h1n1 ) 2009 were identified in south korea during may 2009january 2010 . \n virus isolates from all patients had the h275y mutation in the neuraminidase gene . \n one isolate had the i117 m mutation . \n of the 11 patients , 6 were < 59 months of age , and 5 had underlying immunosuppressive conditions .", "id": 926} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan 18-year - old man was referred to our clinic for the evaluation of blurred vision involving the left eye that had manifested four days previous . he had no specific medical , ocular , or trauma history .\nthe subject 's best - corrected visual acuity was 1.0 in the right eye and 0.9 in the left eye .\nvf ( central 10 - 2 sita - standard strategy ) was measured with a humphrey field analyzer ii ( zeiss - humphrey , san leandro , ca , usa ) under continuous monitoring .\nthe oct demonstrated disruption in the photoreceptor inner and outer segment ( is / os ) junction and undulation of the rpe with backscattering ( fig .\n2c ) , but the oct findings did not reveal improvement compared to the initial findings ( fig .\nthe oct demonstrated a recovery of continuity in the photoreceptor is / os junction , as well as decreased rpe irregularity with minimal backscattering ( fig .\narpe is an acute , transient , foveal disturbance of unknown cause and which affects young adults .\nbecause of scarce case reports and an infrequent prevalence of the disease , the diagnosis can be difficult without suspicion .\nfluorescein angiography ( fa ) is a critical test for the differential diagnosis of arpe .\nunfortunately , we could not obtain fa data because t he patient had signs of an anaphylactic reaction , such as dizziness and difficulty breathing , immediately after the fluorescein injection .\ntherefore , we made a diagnosis based on the fundus findings in combination with the oct and other characteristics of the disease .\nwhite dot syndromes , especially multiple evanescent white dot syndromes ( mewds ) , should be considered in the differential diagnosis of arpe .\nwhite dot syndromes are characterized by multifocal white lesions and are accompanied by mild vitritis .\nmewds differs from arpe in that the lesions are located outside the macula in the posterior pole , and electroretinogram ( erg ) findings are abnormal .\nthe main lesions responsible for mewds cause damage to the photoreceptor outer segment but not the rpe . in our case\n, there was a single white dot lesion that was limited to the juxtafoveal region ; also , erg , which was performed on the first visit , showed normal findings . in acute posterior multifocal placoid pigment epitheliopathy ( apmppe ) ,\nmultiple , large placoid lesions start in the posterior pole and extend to the post - equatorial fundus , often accompanied by prodromal flu - like symptoms . our patient 's lesions were discrete clusters of a few subtle , small grey spots that resolved without scarring within three months after onset .\nin contrast , the lesions in patients with apmppe are replaced by rpe changes upon resolution .\nthe oct demonstrated rpe involvement , which was similar to the previously reported oct findings .\nbased on these findings , other diseases were ruled out and the patient was diagnosed with arpe .\nhsu et al . first described the oct findings of patients with arpe using time domain oct ( oct3 ; carl zeiss ) as a hyper - reflectivity involving the outer nuclear layer , photoreceptor , and rpe .\nhyper - reflectivity has not yet been evaluated with sd - oct . in our case\n, we found a definite disruption in the is / os junction , as well as an undulation of the rpe according to sd - oct .\nbecause sd - oct can provide better image resolution than oct3 , we believe that the disruption of the is / os junction with sd - oct presented as a hyper - reflectivity of the outer retina with oct3 . as reported by hsu et al . , the thickness of the hyper - reflectivity decreased with increased resolution , and we found a decreased length of the is / os disruption based on the serial observations of the oct findings .\nthe rpe irregularity also decreased as the symptoms improved and as the threshold of the visual field increased . on the basis of these findings\n, the morphologic changes in inflammation related to arpe do not seem to be permanent .", "answer": "we investigated the case of a young man with blurred vision in his left eye . \n his visual acuity was slightly decreased , and ophthalmoscopy disclosed a gray - white lesion in the macula . \n he had no systemic or ocular history . \n on the visual field test , the threshold sensitivity was decreased in the corresponding region . \n spectral domain optical coherence tomography ( oct ) demonstrated a disruption in the photoreceptor inner and outer segment ( is / os ) junction and undulation of the retinal pigment epithelium ( rpe ) with backscattering . \n we re - examined the patient after two weeks and after three months without any treatment . visual acuity and visual field results were gradually normalized , and oct demonstrated the recovery of continuity in the photoreceptor is / os junction , as well as decreased rpe irregularity with minimal backscattering . \n we used spectral domain oct instead of time domain oct ( oct3 ) so that we could provide better image resolution of the acute retinal pigment epitheliitis ( arpe ) . \n finally , we observed recovery of the functional and anatomical changes in the arpe patient with a resolution of the condition within three months following the initial examination , using oct and visual field tests .", "id": 927} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nseveral studies reported histophatological observations during influenza a / h1n1 2009 pneumonia : the major finding was diffuse alveolar damage ( dad ) [ 14 ] .\ntype ii pneumocytes were considered the main target of influenza a / h1n1 infection . a limited number of observations described in vivo samples , such as bronchoalveolar lavage ( bal ) [ 68 ] .\ntherefore , it may play a role in further understanding the pathogenesis of new viral strains . in this case\nseries we present the results of bal performed in three patients with severe influenza a / h1n1 2009 pneumonia complicated by acute respiratory distress syndrome ( ards ) .\nbetween august and december 2009 we performed a bronchoscopy - guided bal of three patients admitted to the san gerardo hospital , monza , italy , for influenza a / h1n1 virus pneumonia with subsequent development of ards .\nall three patients required intensive care unit ( icu ) admission and received mechanical ventilation ( mv ) and extracorporeal respiratory support ( ecmo ) .\ninfluenza a / h1n1 diagnosis was confirmed by a / h1n1 virus rna detection on nasal swab samples using influenza a / h1n1 2009 rrt - pcr ( real - time reverse - transcriptase - polymerase - chain - reaction ) assay ( genexpert ) .\nbal differential cell count on cytocentrifugate was performed in the light microscopy ( lm ) by counting about 300 cells in random fields at 400x magnification .\ndemographics , comorbidities , severity on admission , microbiological isolations , and outcome for each patient are described in table 1 .\nantiviral therapy with oseltamivir ( 150 mg twice daily ) was started at hospital admission simultaneously with rrt - pcr assay and was continued until rrt - pcr assay on nasal swab turned negative .\nlarge , atypical cells with plasmocytoid appearance were observed in all three specimens with similar percentages ( 8 , 9 , and 6% , resp . ) . at lm\n, they appeared as large , plasmoblastic / plasmocytoid - like cells with eccentric nuclei and paranuclear vacuoles , high ratio nucleus / cytoplasm , and intensely basophilic cytoplasm .\nimmunocytochemical analysis on cytocentrifugate showed that these cells were negative for cd20 ( b lymphocyte marker ) and cd138 ( plasma cell marker ) .\nultrastructural examinations at transmission em allowed us to observe multilamellar osmiophilic bodies in the cytoplasm of plasmoblastic / plasmocytoid - like cells .\nem showed in these cells small round cytoplasmic inclusions with irregular surface and a diameter around 60 nm ( figure 2 ) .\nthey also showed cytoplasmic vesicles with a diameter around 100 nm and an irregular electron - dense core ( figure 3 ) .\nthe main characteristic of the bal of our patients with influenza a / h1n1 pneumonia associated with ards was the presence of large cells with a plasmoblastic / plasmocytoid - like appearance , identified at em as atypical type ii pneumocytes .\nthe first hypothesis regards the reparative action that type ii pneumocytes may have in dad . in our cases ,\nstanley described morphological atypias , such as increased nuclear - cytoplasmic ratio , in type ii pneumocytes found in bals during ards .\nthese atypical pneumocytes are usually aggregated in clusters and are supposed to have a reparative role .\nall our patients developed ards and we observed pneumocytes aggregated in clusters in the bals performed earlier ( cases numbers 2 and 3 ) . according to this first hypothesis , the atypical cells we observed could be described as reactive immature type ii pneumocytes .\ntype ii pneumocytes have been described as the main target of influenza a / h1n1 2009 infection .\nnakajima et al . in 2012 described four autopsy cases of influenza a / h1n1 with a histopathological pattern of acute dad who presented with influenza virus antigen - positive type ii pneumocytes , perhaps indicating a direct role of the virus - infected cells in the acute alveolar damage .\nno specific cytophatic effect or viral inclusion has been described so far at lm in lung tissue specimens during influenza pneumonia .\nseveral observations have been performed via em on autopsy specimens . during the recent influenza pandemic , mauad et al . found type ii pneumocytes with vesicles , approximately 100 nm in diameter , with an electron - dense center .\nbal and colleagues described cytoplasmic inclusions in pneumocytes , which ranged in diameter from 74 to 82 nm and showed surface spikes characteristic of influenza virus .\nem observations of our specimens revealed some atypical pneumocytes showing both small round cytoplasmic inclusions with an irregular surface and small vesicles ( similar to those described by bal and mauad ) .\naccording to this second hypothesis , atypical type ii pneumocytes could be a specific morphological marker of influenza virus infection . from the data collected so far\n, we can not favor one explanation ; in fact , they could coexist in cases of severe influenza a / h1n1 pneumonia associated with ards .\nlimitations of the present study include the following : first , the paucity of cases analyzed ; second , we did not perform immunohistochemical staining for h1n1 antigens on bal samples . the description of bal in a control group of patients with ards not associated with h1n1 pneumonia is beyond the scope of this case series .\nhowever , other authors described bal cytology in non - h1n1 ards , and although they reported morphological atypias in type ii pneumocytes , they did not describe these peculiar plasmoblastic / plasmocytoid - like cells [ 10 , 12 , 13 ] .\nthe collection of the airway specimens of patients number 2 and number 3 , in which the nosocomial pathogens were isolated , took place after bal was performed .\ntherefore , these pathogens most likely did not affect the cellularity in bal . in conclusion ,\nplasmoblastic / plasmocytoid - like type ii pneumocytes characterize the bal of our patients with influenza a / h1n1 2009 pneumonia associated with ards .\nthey could represent a pathognomonic marker of influenza virus pneumonia as well as reparative cellular activation after dad .\nmore observations of bal cytology in patients with influenza pneumonia are needed to understand their characteristics and role .", "answer": "we present the results of bronchoalveolar lavage ( bal ) performed in three patients with severe influenza a / h1n1 pneumonia complicated by acute respiratory distress syndrome ( ards ) . \n light microscopy analysis of bal cytocentrifugates showed the presence of characteristic large , mononuclear , plasmoblastic / plasmocytoid - like cells never described before . via transmission electron microscopy , these cells were classified as atypical type ii pneumocytes and some of them showed cytoplasmic vesicles and inclusions . \n we concluded that plasmoblastic / plasmocytoid - like type ii pneumocytes might represent a morphologic marker of a / h1n1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage .", "id": 928} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nSynthesis of (\\xc2\\xb1)-Idarubicinone via Global Functionalization of Tetracene\n\nPaper sections:\n\nThe Streptomyces-produced type II polyketides doxorubicin (l)1 and daunorubicin (2)2 are among the most effective and most often used chemotherapeutics owing to their broad-spectrum of anticancer activity (Figure 1).3 For example, doxorubicin (l) is used for the treatment of breast and bladder cancers, childhood solid tumors, soft tissue sarcomas, and aggressive lymphomas.4 Similarly, daunorubicin (2) is primarily used as an antileukemic drug for multiple myeloma, acute myeloid leukemia, acute lymphocytic leukemia, and Kaposi's sarcoma.5 Although extremely effective, anthracyclines threaten patients with cumulative dose-dependent cardiotoxicity, severely limiting their long-term application as well as their use in patients with pre-existing cardiovascular risk.6 Therefore, significant research efforts have been devoted to the identification of derivatives with improved pharmacological properties.7 The successful result of one such medicinal chemistry campaign is idarubicin (3),8 an FDA approved anticancer agent with superior therapeutic efficacy and reduced cardiotoxicity relative to daunorubicin (2).9
The need for tailored analogs has made anthracyclines the subject of rigorous investigation within the synthetic community.10 Thus, many innovative pathways to the aglycon anthracyclines (anthracyclinones) have been established, all of which rely upon annulation to forge one of the rings (see Figure 2a). The most commonly employed unifying disconnection is C-ring annulation, achieved through cycloadditions, cationic cyclizations, or anionic processes (Figure 2a, left inset).11 Moreover, cycloadditions were also explored to forge other rings of the tetracyclic core of these molecules (Figure 2a, right insets).12 Herein, we report a conceptually different, nonannulative approach to anthracyclinones, starting from a simple aromatic hydrocarbon via a global functionalization strategy (Figure 2b). Specifically, (\u00b1)-idarubicinone (4) was synthesized from tetracene (5), an ideal aromatic precursor containing the essential tetracyclic framework, through a manifold of arene functionalizations and a site-selective dearomative elaboration.
Following this global functionalization strategy, we commenced our studies by exploring functionalization reactions of tetracene (5), which would establish the proper oxidation states of the internal rings B and C within idarubicinone (4) (Figure 3). Thus, inspired by a similar transformation reported on anthracene, we achieved the first oxidation of 5 with catalytic amounts of cobalt(II) tetraphenylporphyrin (CoTPP, 5 mol %) and phenyliodine(III) sulfate as an oxidant,13 delivering 5,12-tetracenequinone (6) in 77% yield. Although this transformation proceeded readily, the second oxidation to the corresponding 6,11-dihydroxy-5,12-tetracenequinone derivative 7 proved more challenging. Several oxidants known for direct arene oxidation, such as CAN, Fr\u00e9my's salt, hypervalent iodine reagents, or oxidizing metal complexes,14 were found to be unsuitable for this transformation. This setback was not surprising, as this type of peri-oxidation remains a largely unsolved synthetic challenge owing to the high oxidation potential of quinones. Therefore, we decided to evaluate C\u2013H activation, anticipating that the quinone carbonyl groups would serve as weakly coordinating directing groups for the peri-(C-6) and (C-11) positions15. After examining several carbonyl-directed hydroxylation protocols, we developed a one-pot procedure involving a modification of Ru-catalyzed sp2 C\u2013H oxygenation pioneered by Ackermann ([Ru(cymene)-Cl2]2 and PIFA),16 followed by sequential one-pot hydrolysis and methylation to give desired product 7. Control experiments revealed that this functionalization likely proceeds through the peri-selective formation of ruthenacycle intermediate I-1, delivering phenol derivative, which underwent further oxidation to the hydroquinone stage in the presence of excess PIFA.17
With arene oxidation completed, which set the required oxidation state of the B and C rings, we turned our attention to the dearomative functionalization of the terminal ring A. We have recently reported a series of dearomatization strategies that employ visible-light-promoted para-cycloaddition between arenes and the arenophile N-methyl-1,2,4-triazoline-3,5-dione (MTAD, 8) and subsequent in situ manipulation of the resulting cycloadducts.18 With polynuclear arenes, we consistently observed highly site-selective cycloadditions onto the terminal rings. Because tetracenequinone derivative 7 contains two such regions, rings A and D, amenable to cycloaddition with MTAD, another level of complexity to this process was introduced. However, based on previous studies, we know that the relevant mechanistic feature of this process is a photoinduced charge- and electron-transfer from the arene to the arenophile;19 therefore, the HOMO of the arene should dictate the site-selectivity in polynuclear aromatic settings. Accordingly, computational studies (at the B3LYP/def2-TZVPPD level of theory) of 7 predicted a strong bias for the A ring, which has profoundly larger HOMO orbital coefficients, (see Figure 3, bottom inset for the corresponding HOMO surface). Indeed, this prediction correlated well with experiment, as we observed exclusive cycloaddition onto the A-ring to provide intermediate 9. With this site-selective dearomatization, we explored several strategies to introduce the remaining two carbon atoms needed to complete the idarubicinone framework. We found that the arenophile-based cycloaddition in combination with in situ Rh-catalyzed alkene hydroboration (7 \u2192 [9] \u2192 10) installed the boron moiety as a suitable handle for the introduction of the requisite acetyl group. Several hydroboration procedures were evaluated, but ultimately the cationic rhodium complex [Rh(cod)2BF4] with 1,4-bis(diphenylphosphino)butane (dppb) and catecholborane provided the best outcome (for optimization details, see Table S1 in Supporting Information).20 Although catecholborane was essential for the hydroboration step, the inherent instability of the resulting alkyl catechol boronic ester required immediate transesterification of catechol to pinacol to enable product isolation in higher yields.21 Importantly, following this protocol, we were able to prepare multigram quantities of boronic ester 10 in a single pass in 55% yield and an endo/exo 3:1 dr (see Figure 3, bottom inset for an X-ray diffraction structure of 10).
Elaboration of organoborate 10 to the full skeleton of idarubicinone required installation of a two-carbon fragment through a seemingly straightforward B-alkyl Suzuki coupling reaction. However, since several standard Pd- and Ni-catalyzed reaction conditions failed,22 we decided to explore the C\u2013C bond forming strategies involving the rich chemistry of boron 1,2-metalate rearrangements. Particularly, we were keen to explore Zweifel olefination with lithiated ethoxyvinyl ether,23 which would provide rapid access to the C-9 acetyl group. Nevertheless, a major pitfall of this design was the presence of the quinone and its general incompatibility with organolithium reagents. Indeed, prospecting experiments involving boronic ester 10 and 1-ethoxyvinyllithium resulted in the addition of organolithium species to quinone, delivering a mixture of products without any traces of the desired olefinated product. To address this chemoselectivity issue, we developed a one-pot process that involved in situ masking of the quinone. Thus, a tetrahydrofuran (THF) solution of boronic ester 10 was sonicated with Zn powder in the presence of trimethylsilyl chloride (TMSCl), resulting in the formation of a fully protected bis-hydroquinone.24 This intermediate was exposed to a freshly prepared 1-lithioethyl vinyl ether to form the boronate complex I-2, which was immediately subjected to Zweifel olefination by addition of iodine and base.25 Concurrently with olefination, the excess iodine also oxidized the labile silylated hydroquinone back to the quinone, and workup of the reaction mixture with an aqueous HCl solution hydrolyzed the newly introduced vinyl ether to the corresponding methyl ketone 11. Remarkably, this one-pot operation involved several distinct transformations and was performed on a multigram scale in 72% yield.26
Although the arenophile-mediated dearomative hydroboration and subsequent Zweifel olefination introduced the desired methyl ketone, this sequence also installed a bridging urazole moiety, which had to be strategically transmuted to reveal the fully decorated A ring of idarubicinone (4). This task was partially accomplished by treatment of ketone 11 with base followed by Me2SO4, initiating \u03b2-elimination of urazole at position C-10 with subsequent methylation of the urazole hydrazyl nitrogen, furnishing \u03b1,\u03b2-unsaturated ketone 12 in 79% yield. The N-alkylation of the urazole motif proved necessary to prevent undesired side reactions during subsequent manipulations (for details, see Table S2 in Supporting Information). Finally, subjecting olefin 12 to Mukaiyama hydration conditions27 selectively introduced the tertiary alcohol at position C-9, as \u03b1-ketol product 13 was obtained in 70% yield as a single diastereoisomer. Notably, the use of recently reported silane, PhSiH2(Oi-Pr),28 was beneficial for high conversions of this hydrogen-atom transfer process.
This hydration achieved the proper oxidation state of the A-ring, and the only difference between intermediate 13 and idarubicinone (4) at this stage resided in two hydroquinone protecting groups and the urazole moiety instead of a hydroxy group at the C-7 position. Although deprotection of methyl ethers to hydroquinone proceeded without any difficulties using BCl3 (13 \u2192 14, 98% yield), the removal of the urazole proved to be an arduous task. Eventually, the inspiration for the direct urazole-to-hydroxy exchange was found in the Moore hypothesis for the biological mode of reactivity known as bioreductive alkylation.29 Thus, it was proposed that anthracyclines undergo in vivo quinone reduction and subsequent C-7 amino sugar elimination, producing a reactive species in the form of a phenylogous quinone methide. Moreover, this concept was demonstrated in solution with several anthracyclines, which formed the corresponding semiquinone intermediates upon subjection to specific reducing agents.30 The direct translation of these findings to our system, for example the addition of sodium dithionite to precursor 14, did not eliminate the urazole; however, after the addition of base (NaOH) we observed elimination and exclusive formation of 7-deoxyidarubicinone (15) under anaerobic conditions. This result was in accordance with the literature, since deoxygenated anthracyclinones were commonly observed upon reduction of anthracyclines.31 Mechanistically, the reduction of quinone 14 to hydroquinone, followed by base-induced elimination of the urazole, likely formed the semiquinone methide I-3, which after protonation gave the deaminated product 15. However, we noticed that in the presence of oxygen, this reactive intermediate underwent competitive oxidation,32 delivering idarubicinone (I-3 \u2192 4). Accordingly, short exposure of 14 to an aqueous solution of sodium dithionite and NaOH, followed by rapid saturation of reaction mixture with oxygen, provided (\u00b1)-idarubicinone (4) and (\u00b1)-7-deoxyidarubicinone (15) in 31% and 57% yield. Although extensive optimization of this protocol did not result in a higher ratio of desired anthracyclinone 4 to 15 (for details, see Table S3 in Supporting Information), this deoxygenated side-product could be readily converted to aglycone 4 in one or two steps using known protocols.33
In summary, we have described a functionalization-based approach to (\u00b1)-idarubicinone (4) from tetracene (5). The salient feature of this strategy is a judicious orchestration of two arene functionalizations and dearomatization, introducing the functionality of the A, B, and C rings of the anthracyclinone skeleton. Specifically, Co- and Ru-catalyzed arene oxidations, site-selective arenophile-mediated dearomative hydroboration, and subsequent Zweifel olefination provided the fully decorated anthracyclinone framework. Moreover, adjustment of the A ring, including a formally redox neutral urazole-to-hydroxy exchange delivered (\u00b1)-idarubicinone (4) in 8 operations and 2% overall yield from tetracene (5).
Importantly, by employing a simple polynuclear hydrocarbon aromatic starting material, the described work also presents a notable departure from previously reported syntheses of anthracyclinones in which annulations were critical to the overall synthetic design. In fact, polynuclear arenes are not commonly considered in synthetic planning for construction of stereochemically complex scaffolds. However, through the development and application of new methods, the present study provides a compelling case in which tetracene serves as an ideal template for imprinting of desired functionality. Thus, the range of available polynuclear arenes, as well as numerous functionalization opportunities, can be combined to render this global functionalization approach an appealing and complementary entry for the preparation of other type II polyketide-like compounds.
", "answer": "Anthracyclines are archetypal representatives of the tetracyclic type II polyketide natural products that are widely used in cancer chemotherapy. Although the synthesis of this class of compounds has been a subject of several investigations, all known approaches are based on annulations, relying on the union of properly prefunctionalized building blocks. Herein, we describe a conceptually different approach using a polynuclear arene as a starting template, ideally requiring only functional decorations to reach the desired target molecule. Specifically, tetracene was converted to (\\xc2\\xb1)-idarubicinone, the aglycone of the FDA approved anthracycline idarubicin, through the judicious orchestration of Co- and Ru-catalyzed arene oxidation and arenophile-mediated dearomative hydroboration. Such a global functionalization strategy, the combination of site-selective arene and dearomative functionalization, provided the key anthracycline framework in five operations and enabled rapid and controlled access to (\\xc2\\xb1)-idarubicinone.", "id": 929} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ngastrointestinal stromal tumors ( gists ) are the most common mesenchymal , nonepithelial tumors of the gastrointestinal tract in adults between 40 and 50 years of age [ 1 , 2 ] . as per seer analysis ,\nonly 1% of 1,458 gist cases are esophageal in origin , with an incidence of 5170% in the stomach ; 2536% in the small intestine ; 57% in the colon , rectum and appendix , and 13% in the esophagus [ 1 , 2 , 3 ] .\nthey are generally small and asymptomatic , but occasionally can be large and produce dysphagia . a review of the literature revealed a case of a large esophageal gist presenting with dyspnea .\nhowever , here we report a rare case of a small esophageal gist in a patient with dyspnea who presented with a mediastinal mass on chest x - ray and was initially diagnosed by a pathologist as having leiomyosarcoma and referred for chemotherapy .\n1 ) . a ct scan of the chest with contrast revealed a hypodense , soft tissue mass / lymphadenopathy in the posterior mediastinum measuring 2.0 3.0 cm , contiguous with the esophagus ( fig .\n2 ) , suggestive of neoplastic etiology . further imaging with pet revealed a mediastinal soft tissue mass / lymph node and a standardized uptake value ( suvmax ) of 5.1 .\nthe patient underwent a bronchoscopy and mediastinoscopy with fine - needle aspiration of the mass .\npathology showed increased cellularity with moderate nuclear atypia and pleomorphism with a mitotic count of 23 mitoses/10 high - power fields .\nthe ki67 index was 35% and , finally , the sample was reported as spindle cell well - differentiated leiomyosarcoma ( fig .\nthe patient was referred to us for further management . given the possibility of a gist ,\nthoracotomy findings showed the mass in the posterior mediastinum , which was dissected free from the trachea and inferior aspect of the aorta .\nsix weeks after surgery , a repeated pet - ct scan showed no recurrence . on further follow - up\ngists are rare , accounting for 0.13.0% of all gastrointestinal neoplasms and 5.7% of sarcomas . initially , \ngist applied to neoplasms displaying only c - kit ( cd117 ) , but the diagnosis is based on histopathology and immunohistochemistry .\na total of 95% of gists express kit or dog 1 and have mutations in kit or platelet - derived growth factor receptor , polypeptide .\nthe kit - positive cells in abdominal soft tissues include mast cells in the wall of the gastrointestinal tract ; the interstitial cells of cajal ( intestinal pacemakers ) around the myenteric plexus were thought to be the origin of gists .\ngists typically present in adults 4050 years of age and predominantly in the stomach and intestine .\na comprehensive review of 11 case reports ( table 1 ) and case series with esophageal gists showed that only 1 patient presented with dyspnea and a large posterior mediastinal mass ( 27 cm ) ; 3 further masses were detected on routine chest x - ray [ 3 , 4 ] .\nour patient presented with vague , progressive shortness of breath , with the unusual finding of a small mediastinal mass on chest x - ray .\nesophageal gists commonly present with dysphagia but bleeding , perforation , back pain , anorexia , regurgitation and weight loss have been reported .\ndyspnea with the finding of a small tumor on chest x - ray is rare .\nfurther , pet - ct can help to differentiate gists from sarcoma , but our case showed an suvmax of 5.1 which can misclassify it as sarcoma [ 3 , 8 ] .\ninitial biopsy and testing created a diagnostic dilemma because immunohistochemistry did not include cd117 immunostaining and diagnostic imaging was inconclusive .\nwe present this case to raise physician awareness of such a rare presentation , so that the possibility of gists is considered in these situations , and cd117 testing be done if sarcoma histology is obtained .\nsurgery is the mainstay of treatment of localized gists ; targeted therapies like imatinib have shown overall survival benefit in high - risk patients after surgery [ 9 , 10 ] . and in unresectable and metastatic disease , it has been approved as primary treatment .\nthe pdgfra mutation d842v , sporadic wild - type gists , mutations with succinate dehydrogenase or braf - mutated gists are unlikely to respond to imatinib .\nongoing trials involve sorafenib , nilotinib , pazopanib , regorafenib and cediranib for advanced gists [ 11 , 12 , 13 , 14 , 15 ] .\nfuture trials with combined or sequential use of tyrosine kinase inhibitors with other medications and personalized therapy after tumor molecular subtyping are promising in the management of gists .\nour case report highlights the consideration of gists in the differential diagnosis of posterior mediastinal masses and emphasis on the necessity of cd117 staining in those situations which can alter the therapeutic and prognostic implication for the patient .", "answer": "gastrointestinal stromal tumors ( gists ) are the most common mesenchymal tumors of the gastrointestinal tract and are predominant in the stomach and intestine but rare in the esophagus . here \n , we report a case of esophageal gist which presented as a mediastinal mass on chest x - ray and dyspnea . \n the case was initially diagnosed as leiomyosarcoma , which could create a diagnostic dilemma . therefore , recognizing this uncommon presentation as a mediastinal mass with esophageal gist is important in the differential diagnosis .", "id": 930} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nappropriate placement of dental implants is essential for esthetic and restorative aspects.12 the development of computer - assisted guided surgery has helped realize restoration - driven implant placement.3 contemporary guided implant surgery systems are generally based on cone - beam computed tomography ( cbct ) and computer - aided design and computer - assisted manufacturing ( cad / cam ) technologies .\ncbct visualizes anatomic structures without superimposition , which enables 3-dimensional ( 3d ) diagnosis and treatment planning.456 cad / cam technologies improve the fabrication of surgical guides by reducing manual work and facilitating transfer of the planned implant position to the guide template.7 accurate placement of implants makes it possible to deliver restorations to the patient 's mouth on the day of the surgery.89 accordingly , these advancements have optimized implant treatment to be more predictable , less invasive , and faster from both a surgical and a prosthodontic point of view.1011 surgical guide templates are categorized based on the extent of drilling restriction.12 nonlimiting design is simplistic ; although such guides serve as imaging indicators for marking the entry point of drilling , they do not limit the angulation or the depth of drilling motion .\nhowever , in general , hole enlargement and implant placement are still performed freehand by the surgeon .\nmost surgical guides with partially limiting design are converted from a radiographic template that is used to evaluate the surgical bone site and devise a surgery plan . completely limiting design\nis the most advanced type of guide , restricting the drilling process and placement of implant in three dimensions .\nthis design concept reduces the need for decision making during surgery , thereby leading to more predictable results of implant placement .\ncontemporary cad / cam - based surgical guides are included in this category.1314 the accuracy of a guided implant surgery system is defined as the deviation between the planned and placed position of the implant.15 the accuracy of the entire procedure is a quantitative evaluation of positional and angular discrepancies in 3d coordinates.16 the measurements are performed using image superimposition of pre- and postoperative ct images.17 possible sources of error include factors such as digitizing , superimposition , machining process , the guide design concept , and the operator 's experience .\n1819 in a recent in vitro study , van assche and quirynen reported a noticeable tolerance of surgical implant instruments within the metal sleeve.15 this tolerance is caused by the gap between the drill and the guide sleeve , which allows rotation of the drill in the sleeve .\nunwanted lateral osteotomy may occur when the drill is not parallel to the sleeve during the drilling ; therefore , this type of error is defined as an intrinsic error.20 on the other hand , if there is no tolerance , the friction generated from mechanical components hinders the drilling process , which might result in sleeve deformation .\nrecently , a direct drill - guiding implant surgery system with a completely limiting design was developed .\nthis system features shank - modified drills that use the shank portion of surgical instruments as a guiding component to limit drilling motion with little tolerance .\nmoreover , a guide sleeve is incorporated in the stereolithographic surgical guide design , which eliminates the need for additional insertion of metal guide sleeves into the guide template .\nthe purpose of this study was to investigate the accuracy of this newly developed guided implant surgery system in partially edentulous patients using prospective clinical design and geometric analyses.2122\neleven patients ( 5 men , 6 women ; aged 2175 years ; mean age 46 years ) requiring implant placements in partially edentulous jaws were included in this study .\na total of 21 implants ( anyone ; megagen implant , gyeongbuk , korea ) were placed .\npatients with a history of debilitating systemic disease or requiring ridge augmentation with bone grafting were excluded from the study .\nthe study was approved by the institutional review board of the hospital ( 2014 - 11 - 020 ) .\na conventional impression was taken , and a stone cast was fabricated for each patient .\nthe surface image of the cast was then digitized into surface tessellation language ( stl ) format using a desktop scanner ( ceramill map 400 ; amann girrbach , koblach , austria ) .\nimages of the underlying bone were obtained using a cbct scanner ( pax - flex3d ; vatech co. , hwasung , korea ) with a field of view of 120 85 mm , voxel size of 0.2 mm , and exposure conditions of 90 kvp , 10 ma , and 24-second pulsed scan . during cbct image taking , patients were directed to bite a radiopaque datum tray ( megagen implant , gyeongbuk , korea ) in centric occlusion .\nthe cbct data were saved in digital imaging and communications in medicine ( dicom ) format .\nthe datum tray was also digitized into a stl file using the desktop scanner ( ceramill map 400 ; amann girrbach , koblach , austria ) .\nthe solid block portion of the datum tray was used as a medium for superimposition of the surface image and underlying bone image .\nthe dicom file and the two stl files were imported into an implant - planning software program ( r2gate 1.0 ; megagen implant , gyeongbuk , korea ) where the image merging and virtual surgery were performed .\nthe image - merging process was performed with manual registration by selecting three anatomic landmarks from the dentition .\nthe position of the implant was determined based on the underlying bone and virtual restoration ( fig .\n2 ) and fabricated using a 3d printer ( perfactory 4 ddp ; envisiontec , dearborn , mi , usa ) .\nthe direct drill - guiding system in this study uses shankmodified drills whose structure has 3 parts : the stopper part , the guide part , and the drilling part ( fig .\nthe stopper structure of the drill corresponds with the stepped structure of the internal surface of the sleeve and restricts the drilling depth when the two structures are joined .\nthe guide part of the drill closely accommodates the sleeve of the guide , which limits the orientation of the drilling motion .\nthe guide part of the drill has the uniform diameter and length ; this feature eliminates the need for additional internal tubes .\nthe handpiece connector and ratchet connector are instruments for inserting the implant fixture after osteotomy . as the component for depth control , the handpiece connector has the stopper structure , and the ratchet connector has a horizontal marking to indicate the correct depth of insertion .\nthe sleeve structure of this system is incorporated into the design of the guide template , so the guiding component is created together with the guide body when the template is fabricated ( fig .\neach drilling was performed until the stopper of the drill contacted the rim of the guide template .\nall implants were placed by a single operator . to obtain the positional information of the placed implant , postoperative cbct scanning was conducted using the same settings as the preoperative scan .\nthe accuracy of the guided surgery system was evaluated at the abutment level by comparing the virtual abutments of the planned and placed implants ( fig .\nthe actual position of the abutment was determined based on the actual position of the implant in the postoperative cbct scan .\nthe outcome parameters were horizontal deviation , vertical deviation , and angular deviation , and the values were calculated using the centerlines of the abutments and reference points in 3 dimensions .\nall data were reported as the mean standard deviation and visualized via bar graphs .\nthe kruskal - wallis test and mann - whitney u test were used to compare the amounts of deviation among 3 planes .\nthe means and standard deviations of horizontal deviation were 0.593 0.238 mm in the mesiodistal direction and 0.691 0.344 mm in the buccolingual direction .\nthe mean vertical deviation was 0.925 0.376 mm in the occlusogingival direction , which was significantly larger than the horizontal deviations ( p = .018 ) .\nhowever , there was no significant difference between the two horizontal deviations ( p = .421 ) .\nas for angular deviation , the values were 2.024 0.942 degrees in the mesiodistal direction and 2.390 1.142 degrees in the buccolingual direction ( fig .\nthe direct drill - guiding system in this study showed higher accuracy in implant placement by using shank - modified drills and a stereolithographic surgical guide that reduces the tolerance of surgical drills inside the guide sleeves . in a recent systematic review ,\nthe mean horizontal deviation of implant placement compared to the planned position was reported as 1.2 mm,23 whereas the direct drill - guiding system showed a mean deviation of 0.642 ; thus , this system is approximately twice as accurate as other systems in terms of horizontal linear deviation .\nthe angular deviation of the direct drill - guiding system in this study was less than the general value of angular deviation reported in the systematic review .\nthese findings correspond well with those reported by cassetta et al.,14 who evaluated the effects of limiting the tolerance between the drill and guide sleeve on the total error of implant placement .\nto minimize tolerance , two tubes were used ; a guide tube was attached to the head of the surgical handpiece , and a master tube was embedded in the surgical guide . because the diameter of the guide tube was only 0.05 mm smaller than that of the master tube , these tubes fit closely during the drilling procedure .\nthese mechanics allowed only in - and - out motion , restricting the lateral movement of the drill . as a result ,\nthe accuracy of the system with the guide tube was superior to that of the system without the guide tube .\nthe direct drillguiding system in the present study has a similar mechanism for reducing tolerance .\ntherefore , it can be inferred that the direct guiding components play a key role in limiting drill movement and that tolerance control is essential for increasing the accuracy of the guided surgery system .\neven when the sleeve of the guide template limits the blade part of the drill , a certain amount of gap is inevitable to allow the rotation of the drill within the sleeve.20 the deviation caused by the gap when the drill is not turning can be calculated theoretically by the interrelationship between the sleeve and drill angulation.24 basically , to increase the positional concordance of the planned and placed implants , it is important to use the drill in a centric position and parallel to the internal wall of sleeve.71525 however , it is not easy to keep a drill in the correct position because visibility and manipulability of the drill is limited in the narrow intraoral space .\nmeanwhile , the use of longer sleeves has been suggested as a mechanical approach to reduce the tolerance of surgical instruments .\nalthough the above - mentioned parallel drilling and use of longer sleeves are helpful for increasing the accuracy of implant placement , the sleeve should still have some amount of tolerance to prevent friction when the drill is rotating .\nin other words , the gap between the drill and the guide sleeve is unavoidable , which leads to errors in implant placement . as an alternative for guiding a drilling part of drill through a sleeve ,\nkoyanagi26 suggested the use of two orthodontic wires and tubes to connect the head of the handpiece with the guide template . since the wires slide along the tube , the drill advances as planned during the osteotomy .\nthe guide system tested in the present study is based on a different working mechanism and consists of modified drills that use the shank part of drill as a guiding surface . since the guiding surface makes direct contact with the inner surface of sleeve , the tolerance of the drill is markedly decreased .\nthis direct contact can be maintained during drill rotation because both contact parts have smooth surfaces with low the friction coefficient .\nthe combination of the shank - modified drill and sleeve - incorporated stereolithographic guide template therefore completely restricts the implant instruments and leads to more accurate implant placement .\nthe depth control of instruments is an essential element of a guide system with a completely limiting design.27 the addition of a stopper physically restricts the depth of the osteotomy by allowing drill advancement only to the level of the stopper.2829 this depth control enhances safety by preventing drills from intruding on vital anatomic structures such as the maxillary sinus and inferior alveolar nerve.30 the stopper is also useful for placing the implant at the planned depth , which not only improves treatment convenience but also enables immediate placement of the coronal restoration.31 in general , the mean vertical error of previous implant guide systems was reported as 0.5 mm.19 however , the guide system in the present study showed less accurate outcomes in the depth parameter .\nalthough the ratchet connector has a reference line to indicate the stop point , it lacks a physical stopper .\naccordingly , the vertical positioning of implant is influenced by the operators ' visual and tactile senses .\nthus , to improve the accuracy of this system in the vertical dimension , inclusion of a stopper structure on the ratchet connector is recommended .\nthe accuracy of guided implant surgery is influenced by procedures that transfer the digital virtual plan to the surgical site.19 possible individual errors originate from intrinsic sources , which include issues with radiography quality , file conversion , cad software , and the tolerance between mechanical components ; and extrinsic sources , which relate to the fit of surgical guide , the mucosal thickness at the surgical site , the position of the edentulous area , and the surgeon 's experience .\nthis study revealed the error in the accuracy of the newly developed guided implant surgery system . since the data were obtained from clinical cases , the outcome values are clinically valid and meaningful .\nthus , controlled in vitro experiments or large - size clinical prospective trials will be needed in the future to analyze these effects .\nto our knowledge , this is the first clinical report to evaluate the accuracy of a direct drill - guiding system for implant placement .\nthe present study confirms that the use of shank - modified drills and sleeve - incorporated stereolithographic templates is an effective way to improve the accuracy of implant placement by minimizing mechanical tolerance of the instruments .", "answer": "purposea recently introduced direct drill - guiding implant surgery system features minimal tolerance of surgical instruments in the metal sleeve by using shank - modified drills and a sleeve - incorporated stereolithographic guide template . \n the purpose of this study was to evaluate the accuracy of this new guided surgery system in partially edentulous patients using geometric analyses.materials and methodsfor the study , 21 implants were placed in 11 consecutive patients using the direct drill - guiding implant surgery system . \n the stereolithographic surgical guide was fabricated using cone - beam computed tomography , digital scanning , computer - aided design and computer - assisted manufacturing , and additive manufacturing processes . \n after surgery , the positional and angular deviations between planned and placed implants were measured at the abutment level using implant - planning software . \n the kruskal - wallis test and mann - whitney u test were used to compare the deviations ( =.05).resultsthe mean horizontal deviations were 0.593 mm ( sd 0.238 ) mesiodistally and 0.691 mm ( sd 0.344 ) buccolingually . \n the mean vertical deviation was 0.925 mm ( sd 0.376 ) occlusogingivally . \n the vertical deviation was significantly larger than the horizontal deviation ( p=.018 ) . \n the mean angular deviation was 2.024 degrees ( sd 0.942 ) mesiodistally and 2.390 degrees ( sd 1.142 ) buccolingually.conclusionthe direct drill - guiding implant surgery system demonstrates high accuracy in placing implants . \n use of the drill shank as the guiding component is an effective way for reducing tolerance .", "id": 931} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\neosinophilic gastritis is an extremely rare disease that is characterized by eosinophilic infiltration of the various layers of the gastrointestinal tract in the absence of any definite causes of eosinophilia .\npatients with eosinophilic gastritis have diverse symptoms , including abdominal pain , emesis , abdominal distension , and weight loss .\nthese symptoms are associated with eosinophilic infiltration of the various layers of the gastrointestinal tract .\nthe disease has to be distinguished from generalized eosinophilic disorder presenting with involvement of other organs .\na 52-year - old female patient visited another hospital because of epigastric pain and tenderness .\nshe had no history of allergic diseases such as eczema or atopy , or food or drug allergies .\n, she had undergone esophagogastroduodenoscopy ( egd ) , which revealed multiple focal ulcerative lesions with diffuse discoloration and edematous change of the rugae in the gastric fundus , cardia , and upper body ( fig .\nthe symptoms had been recalcitrant to treatment with proton pump inhibitors , fasting , and fluid .\nshe had reported no nausea , vomiting , hematemesis , or melena . on admission ,\nher blood pressure was 110/60 mm hg , pulse rate 76 beats per minute , respiratory rate 22 breaths per minute , and body temperature 36.2. physical examination revealed tenderness of the epigastric area .\nher white blood cell count was 22,770/mm with markedly increased eosinophils ( 5,009/mm , 22% ) .\nthe c - reactive protein concentration was 13.95 mg / dl . her other blood chemistry test results were normal .\nthe tests for viral markers included hepatitis a , b , and c virus and human immunodeficiency virus ; those for autoimmune antibodies included anti - nuclear , anti - double stranded dna , and anti - neutrophilic cytoplasmic antibodies ; and those for tumor markers included -fetoprotein , carbohydrate antigen 19 - 9 , and carcinoembryonic antigen .\nthe serological test for toxocara antibodies ( igg ) was positive , whereas those for echinococcus , paragonimus westermani , sparganumi , and trichinella antibodies were negative .\nthe chest and abdomen radiographic examinations were normal . to investigate the cause of the epigastric pain and tenderness ,\nabdominal computed tomography was performed , which revealed severe edematous wall thickening with focal localized low attenuation of the fundus and cardia of the stomach ( fig .\nshe underwent a repeated egd , which showed diffuse necrotic change in the fundus , cardia , and upper body ( fig .\na biopsy specimen was obtained during egd ; a rapid urease test ( clotest ) revealed no evidence of helicobacter pylori . on histopathologic evaluation ,\nthe gastric surface was found to be eroded and the underlying lamina propria showed dense eosinophilic infiltration .\nshe was treated with empirical intravenous antibiotics ( cefoperazone and metronidazole ) immediately after her transfer because infectious gastritis was not ruled out .\nalthough she was treated with a broad - spectrum anthelmintic ( albendazole ) , antibiotics , proton pump inhibitor , and prokinetic agent during the next 5 days , her symptoms became worse .\neosinophilic gastritis was diagnosed according to the clinical pictures , laboratory findings , and endoscopic findings .\nshe was immediately started on methylprednisolone ( 62.5 mg / day ; this dose was maintained for 7 days ) .\ntherefore , she underwent a repeated short - term follow - up egd that showed regenerative epithelial tissue with peeling off , of the necrotic tissue ( fig .\nshe underwent a repeated egd that showed the replacement of white color scar tissue ( fig .\ncurrently , she is being treated with 30 mg / day prednisone and is showing considerable clinical improvement .\neosinophilic gastroenteritis is an uncommon and rarely reported disorder characterized by eosinophilic infiltration of the various tissue layers of the digestive tract in the absence of any definite causes of eosinophilia , without eosinophilic infiltration in other organs .\nthe diagnosis of eosinophilic gastroenteritis is based on the following criteria : the presence of gastrointestinal symptoms , histological presentation of eosinophilic infiltration in tissue layers of the digestive tract , presence of high eosinophil count in ascites , and no evidence of parasitic infection or eosinophilic involvement of extraintestinal organs .\neosinophilic gastroenteritis can involve any portion of the gastrointestinal tract from the esophagus to the rectum , and the stomach is the most commonly involved organ , especially the antrum . in eosinophilic gastritis ,\nthe endoscopic features are rather extensive : rugal fold thickening , erythema , friability , nodularity , gastric outlet obstruction , gastric ulcer , and even a normal mucosa .\nalthough not clearly defined , the common pathophysiological mechanism of this disease is associated with eosinophilic infiltration and degranulation in specific tissue layers of the digestive tract .\nthis eosinophilic recruitment and activation regulated by diverse cytokines is a part of the host immune mechanism in the gastrointestinal mucosa ; however , it can be a type of serious allergic or inflammatory reaction in the deeper tissue layers of the gastrointestinal tract . although there is no treatment consensus on eosinophilic gastroenteritis ,\nseveral studies report good results with steroids in dosages from 20 to 40 mg / day , for 6 to 8 weeks [ 7 - 10 ] . in some case studies ,\nleukotriene modifiers such as montelukast or mast cell stabilizers such as sodium cromoglycate have been proposed to be helpful for symptomatic improvement .\nantihistamines such as ketotifen or immunosuppressants such as mycophenolate mofetil are also used in the treatment of eosinophilic gastroenteritis ; however , their therapeutic effects are not clear and would require more studies .\nalthough rare , eosinophilic gastritis should be considered in the differential diagnosis of patients with gastrointestinal symptoms and peripheral blood eosinophilia .\nlymphoma of the stomach , gastric cancer , and crohn disease involving the stomach may demonstrate endoscopic features similar to those of eosinophilic gastritis .\ngastrointestinal parasitic infection should be considered in patients with abdominal discomfort , weight loss , and peripheral eosinophilia . in particular , infestations by hookworms ,\nascaris , strongyloides , toxocara , trichuris , and intestinal capillaria should be considered in patients from endemic areas . in this case , the concentration of the antigen - specific ige to the a. simplex was 0.57\nmoreover , the serology for toxocara antibodies ( igg ) was positive . however , this is not clinically significant in korea because koreans often consume raw fish , which causes repeated exposures to anisakis .\nin addition , she had not had contact with any animals , including dogs and cats , at least for several years .\nmoreover , she was treated with albendazole for 5 days , and her symptoms had become worse . after steroid treatment , the symptoms disappeared and the eosinophil count decreased to the reference range .\nmoreover , the follow - up egd showed regenerative epithelial tissue with peeling off , of the necrotic tissue\n. she had undergone several egds that showed diffuse necrotic change in the fundus , cardia , and upper body .\nthe etiology includes thromboembolism and occlusion of major arterial supply , ingestion of corrosive agents , volvulus of the stomach , endoscopic hemostatic injections , and infectious gastritis . in this case\nthus , the possible cause of gangrene could be infection , and she was treated with empirical intravenous antibiotics ( cefoperazone and metronidazole ) .\nhowever , she was treated with broad - spectrum antibiotics during the next 5 days , and her symptoms became worse .\nthe necrotic portion of the gastric high body is very vulnerable site of retching injury .\nthis retching injury is called prolapse gastropathy syndrome , a clinical syndrome involving the invagination of part of the gastric mucosa into the lower esophagus .\ndirect trauma to the mucosa occurs when the gastric mucosa becomes incarcerated through the lower esophageal sphincter .\nin addition , the endoscopic findings and histopathologic results were not compatible to prolapse gastropathy syndrome . on the basis of the clinical picture , laboratory findings , and therapeutic results , we concluded the diagnosis of eosinophilic gastritis presenting as necrotizing gastritis in our patient .\nthis case highlights the reality of eosinophilic gastritis presenting as necrotizing gastritis , and that endoscopy and histopathological examination of the biopsies are the most useful tools for the diagnosis of eosinophilic gastritis presenting as necrotizing gastritis .\neosinophilic gastritis should be considered in the differential diagnosis in patients with necrotic gastritis who do not respond to empirical treatment .", "answer": "eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia . \n it is associated with various clinical gastrointestinal manifestations , and depends on the involved layer and site . \n we report a case of eosinophilic gastritis presenting with severe necrosis . \n the symptoms disappeared immediately after beginning steroid treatment , and the eosinophil count decreased to the reference range . \n the patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis . \n it is a unique presentation of eosinophilic gastritis . to the best of our knowledge , \n no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in korea .", "id": 932} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nroad traffic crash ( rtc ) is the main cause of non - intentional injuries and the second cause of deaths after ischemic heart diseases in iran .\nit accounts for more than 10% of total mortalities and about 23,000 deaths , in average , per year during the last decade .\nthis is approximately equal to the number of deaths caused by the 2003 bam earthquake , one of the worst natural disasters of recent decades .\nthese facts have made the rtc as a man - made disaster and real public health concern in iran . in line with the fourth i.r .\niran 's national development plan ( ndp ) , the fifth ndp for 2011 - 2015 has emphasized on development of rural infrastructures , including rural asphalt roads . although this development has led to more traffic in rural roads , no significant improvement is observed in safe driving behavior and construction of roads in rural areas .\nin addition , compared with urban areas , rural people use older cars with less safety standards .\nthe monitoring by traffic police and coverage of emergency medical services ( ems ) are also lower in rural roads than main roads . this article aims to provide the iranian policy makers with information on the burden of deaths that are caused by rural rtcs and demonstrates its association with expansion of the rural roads .\nwe applied a retrospective analysis of secondary data to demonstrate the association of rural rtcs deaths with expansion of the rural roads in iran .\nthe variables of interest included length of road ( rural and urban ) , number of death ( caused by rural and urban rtcs ) and number of population .\nthe sources that we used for data collection were the iran 's high commission of road safety ( hcrs ) for length of road ( km ) , the iran 's forensic medicine organization ( fmo ) for the number of rtcs death and the iran 's statistical center for population data .\ninternational classification of diseases-10 is the basis for coding the causes of death by fmo . for the purpose of analysis\n, we illustrated the trends of length of rural road from 2005 to 2010 and their corresponding mortality .\nrates of traffic death in rural and urban roads were also estimated per 100,000 populations .\n for trend was the test of significance and p < 0.05 was considered as statistically significant .\nspss statistical software for windows ( version 11.0 , chicago , il ) was used for statistical analysis .\nthe number of rtc deaths in rural roads increased from 1,672 in 2005 to 2,206 in 2010 .\nthis was parallel to construction of the rural asphalt roads that was increased from 56,424 to 86,519 km during the same period [ figure 1 ] .\nthe trend analysis showed a positive association between these two variables ( for trend = 3.93 , df = 1 , p = 0.04 ) .\nlength of rural asphalt roads and number of deaths caused by rural road traffic crashes , iran , 2005 - 2010 the expansion of urban asphalt roads was also on an increasing trend from 71,711 to 77,964 km , but the number of traffic deaths in these roads decreased from 26,083 in 2005 to 21,043 in 2010 . from 2005 to 2010 , adjusted for 100,000 populations , the number of traffic deaths in urban roads decreased from 37.0 to 28.0 , while this number increased from 2.4 to 2.9 in rural roads [ figure 2 ] .\nour study showed an increasing trend of the rtc deaths in iran 's rural roads and its positive association with expansion of the rural roads .\nthis is while , at the same period , the rate of traffic death in urban roads was on a decreasing trend .\ntherefore , expansion of the road network is one of the most important prerequisites for development of economics and infrastructures in rural areas , the policy makers should take preventive measures in rural roads to improve the safe driving condition . in this line ,\niran 's ministry of road and urban construction is the lead agency for the hcrs .\ntraffic police , ems and car factories are the main stakeholders of this national coordination body . to reduce the rate of deadly traffic crashes in rural roads , taking the coordinated measures by the hcrs ' members\nthe hcrs may also rely on the successful experience in decreasing the rate of urban rtc deaths . according to available literature ,\nthe risk factors of deadly rtcs in rural roads of iran are unsafe roads , excessive speed , risky driving caused by inadequate knowledge and inappropriate risk perception , no use of seat belt and using of old cars with low safety equipments .\neffectiveness of the enforcement measures for control of rtcs in iran is rated six out of 10 , according to the world health organization .\nthis is expected to be even lower in rural roads as they are less controlled by traffic police compared with freeways , highways and main roads .\ntimely and quality provision of medical care is essential for saving lives in a rtc . in 2010 ,\nthe national emergency medical service was only able to cover 15% of minor roads , including rural areas . according to national ems , in addition to the current 1,028 ems stations ,\nrural rtc is a concern not only in developing countries like iran , but also it accounts for the considerable number of death in developed countries . for instances , in germany ,\nbritain and the us , about two third of all rtc related fatalities occur on rural roads , which score badly when compared to the high quality motorway network in those countries .\nall these have said , there are evidences that fortunately show how the preventive measures can be effective in reducing rural rtcs . for example , in germany , reinforcement of speed limits and development of additional passing lanes were found effective .\nthe expansion of rural asphalt roads exposes the people of rural areas with risk of severe rtc if effective preventive measures are not taken . to prevent from this threat , the iranian policy makers need to take the followings into consideration : public awareness , improving the safety of roads and vehicles , law enforcement , increasing coverage of police and ems", "answer": "background : the 5th iran national development plan , 2011 - 2015 , has emphasized on expansion of rural asphalt roads . this article aims to illustrate the trend of deaths caused by rural road traffic crashes ( rtcs ) and its association with length of the rural roads in iran.methods:we carried out a retrospective analysis on secondary data for the period from 2005 to 2010 . the iranian forensic medicine organization , high commission for road safety and iran 's statistical center were the sources for the number of rtc death , length of the road and population data , respectively.results:number of rtc deaths in rural roads increased from 1,672 in 2005 to 2,206 in 2010 \n . \n this was associated with expansion of the rural asphalt roads ( p = 0.04 ) . \n the construction of urban asphalt roads was also on an increasing trend , but the number of traffic deaths in these roads decreased from 26,083 in 2005 to 21,043 in 2010 . \n adjusted for 100,000 populations , the number of traffic deaths in urban roads showed a decrease from 37.0 to 28.0 , while this number increased from 2.4 to 2.9 in rural roads during the study period.conclusions:although expansion of rural roads would contribute to economic development in rural areas , it exposes people to risk of severe rtcs if effective preventive actions are not taken . to prevent this threat \n , the iranian policy makers need to take the followings into consideration : public awareness , improving the safety of roads and vehicles , law enforcement , increasing coverage of police and emergency medical services .", "id": 933} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndespite a considerable progress in malaria control in iran over the past few years that led to significant reduction of cases , the disease still remains a major health problem in south and southeastern parts of the country .\n2008 , afsharpad et al . 2012 ) and insecticide resistance of anopheles vectors ( enayati et al .\n2012 ) are aggravated by continuous influx of imported cases , mostly with plasmodium falciparum , from neighboring countries of afghanistan and pakistan ( zakeri et al .\nthe latest checklists of iranian mosquitoes include 28 anopheles species , identified mostly on the basis of morphological features , and a few by dna - based approaches ( azari - hamidian 2007 ) .\nmaculipennis are known to be responsible for transmission of malaria in the country ( manouchehri et al .\nsome important malaria vectors in iran are assumed to be members of species complexes or species groups , which are often difficult to distinguish morphologically .\napplication of dna - based approaches has resolved some cryptic species in iranian complex species including an .\nfluviatilis , however , the identity of some members are still doubtful or were refuted later ( azari - hamidian 2007 , naddaf et al .\nthis , to great extent , is due to introduction of molecular markers such as its2 and 28s - d3 genes for discriminating the members of this complex species in india ( manonmani et al .\nbiology , variation in behaviors , and role of this species in malaria transmission in different geographical areas of iran has been extensively reviewed by others ( eshghi et al .\n1976 , edalat 19971998 , hanafi - bojd et al . 2012 ) . in an early study comparison of its2 sequence of iranian specimens from various localities in south and southeastern\niran revealed only species y , which is presumably species t ( naddaf et al . 2003 ) , however , rapd - pcr analysis of same specimens revealed two distinct patterns , separating representatives of fars province from other areas ( naddaf et al .\nanalysis of 28s - d3 gene from same populations corroborated rapd results , fars province specimens showed to be identical to species u in india , while individuals from other areas exhibited heterozygocity at the only base pair position that identifies species u and t ( naddaf et al . 2010 ) .\nin addition , in a separate study based on 28s - d3 analysis , species t and species u were reported from jiroft of fars province and chabahar of sistan va baluchestan province , respectively ( mehravaran et al . 2011 ) .\nthe aim of this study was to evaluate cytochrome oxidase i ( coi ) gene alongside 28s - d3 as a diagnostic tool for identification of an .\ncoi gene sequences have been extensively used for population studies and resolving evolutionary relationship among closely related species groups of insects ( lunt et al . 1996 ) and\nanopheline mosquitoes ( krzywinski and besansky 2003 ) . variations in this fragment have been exploited as dna barcodes for identifications of culicidae mosquitoes including an .\nfluviatilis mosquitoes originated from different localities in south and southeastern areas of iran including fars , hormozgan , kerman , and sistan va baluchestan provinces .\nthe extraction method and identity of some mosquitoes based on its2 and/or 28-d3 genes were described previously ( naddaf et al .\nall the dna samples were initially subjected to allele specific ( as)-pcr based on 28s - d3 gene as described by singh et al .\nthe coi gene was amplified using universal primers , ubc6 ( 5- gga gga ttt gga aat tga tta gtt cc -3 ) and ubc9 ( 5-ccc ggt aaa att aaa ata taa act tc-3 ) , designed by simon et al .\neach 25l reaction contained 20 pmol of each primer , 2 mm mg cl2 , 10 mm tris - hcl , 50 mm kcl , 150m of dntps , 1u of taq , and 2l of dna .\npcr products were purified using a gel band purification kit ( pharmacia , piscataway , nj , usa ) according to manufacturer s recommendations and later sequenced using the same primers as used for amplification at seqlab laboratory in germany .\nthe sequences were manually edited and corrected using bioedit software , version 7.1.3.0 ( hall 1999 ) and fragments of 474 bp length were selected for analysis .\nthe distances between groups and between individual sequences were calculated , and phylogenetic tree for iranian sequences was generated using the kimura two parameter ( k2p ) model of neighbor - joining method in a complete deletion procedure using mega 4 software ( tamura et al .\nthe sequence data for the coi gene sequences were submitted to genbank with the accession numbers jx020706-jx020729 .\nfluviatilis mosquitoes originated from different localities in south and southeastern areas of iran including fars , hormozgan , kerman , and sistan va baluchestan provinces .\nthe extraction method and identity of some mosquitoes based on its2 and/or 28-d3 genes were described previously ( naddaf et al .\nall the dna samples were initially subjected to allele specific ( as)-pcr based on 28s - d3 gene as described by singh et al .\nthe coi gene was amplified using universal primers , ubc6 ( 5- gga gga ttt gga aat tga tta gtt cc -3 ) and ubc9 ( 5-ccc ggt aaa att aaa ata taa act tc-3 ) , designed by simon et al . (\neach 25l reaction contained 20 pmol of each primer , 2 mm mg cl2 , 10 mm tris - hcl , 50 mm kcl , 150m of dntps , 1u of taq , and 2l of dna .\npcr products were purified using a gel band purification kit ( pharmacia , piscataway , nj , usa ) according to manufacturer s recommendations and later sequenced using the same primers as used for amplification at seqlab laboratory in germany .\nthe sequences were manually edited and corrected using bioedit software , version 7.1.3.0 ( hall 1999 ) and fragments of 474 bp length were selected for analysis .\nthe distances between groups and between individual sequences were calculated , and phylogenetic tree for iranian sequences was generated using the kimura two parameter ( k2p ) model of neighbor - joining method in a complete deletion procedure using mega 4 software ( tamura et al .\nthe sequence data for the coi gene sequences were submitted to genbank with the accession numbers jx020706-jx020729 .\nall the dna specimens from fars province yield only a product of approximately 375 bp length indicative of species u , whereas specimens from hormozgan , kerman and sistan va baluchestan provinces amplified two bands of 375 bp and 128 bp length .\nphylogenetic analysis using coi gene grouped individuals from fars province in two distinct clades separate from other iranian individuals representing populations of hormozgan , kerman , and sistan va baluchestan ( fig .\nthe mean distance between iranian and indian groups was 1.66% , while the value between fars group and the group comprising other iranian members was 2.06% .\nthe indian group exhibited the same distance ( 2.06% ) with fars group . the highest distance ( 3.09% ) among iranian individuals was between specimens 930 from fars province and 398 from sistan va baluchestan province .\nsix individuals belonging to two clades ( 87 , 97 , 655 , and 928 ) and ( 92 ) from fars province showed 100% identity .\nin addition , ten individuals from other geographical areas including four from koveh ( 170 , 172 , 173 , and 186 ) and one from minab ( 121 ) in hormozgan province , two from abchekan ( 392393 ) in sistan va baluchestan province , and three from kahnouj in kerman province ( 815 , 836 , and 839 ) were 100% identical .\naccurate identification of malaria vectors is not only one of the most basic requisite for success of malaria control programs , but also has become an intriguing issue for understanding speciation process and evolution of anopheles mosquitoes . in absence of cytotaxonomic evidence , rapd - pcr methodology and variation in 28s - d3 gene have resolved two potential sibling species in an .\nwe report further evidence for the occurrence of these two sibling species by coi analysis of mitochondrial dna from the same specimens .\nanopheles fluviatilis james is a complex of cryptic species ; cytotaxonomic studies of polythene chromosomes has revealed three reproductively isolated species in india known as s , t , and u ( subbarao et al . 1994 ) .\napplication of the first dna - based method using its2 gene identified two putative species of x and y that are presumably equivalent to species s and t , respectively ( manonmani et al .\nlater , a complete as - pcr assay based on variations of 28s - d3 gene against chromosomally examined specimens identified all the members of the complex ( singh et al .\nfluvialitis mosquitoes of iran . however , the same specimens displayed variations in 28s - d3 gene ; the individuals from fars exhibited similarity with species u in india whereas individuals from others areas showed heterozygocity at the single nucleotide position that identifies species u and t. the identity of an .\nfluviatilis complex in iran became complicated as the heterozygocity in 28-d3 was not reflected in its2 fragment and individuals from fars province exhibited dual identity of t and u based on its2 and 28s genes , respectively ( chen et al .\nfluviatilis sibling species were not addressed in their study , however , k2p genetic distances between different species of culicidae were reported to be > 2% . in our study , the mean distance between iranian and indian populations was 1.66% , whereas the value between fars group and the group comprising other iranian individuals was 2.06% .\nthe distance between most individuals from fars province and individuals from other areas was > 2% .\ntwo individuals ( 9192 ) from fars province exhibited almost equivalent distance with all other members including those ( 930 , 926 , 928 , 655 , 87 , and 97 ) from the same province .\njf966741 , unpublished ) that showed a high divergence from other sequences and appeared as an out group beyond an .\nthe results of present study were almost concordant with earlier results obtained by rapd - pcr methodology and 28s - d3 analysis ( naddaf et al .\nthis study shows that coi gene can be used as a useful tool along other dna markers like 28-d3 gene for dissolving closely related taxa of an .\nfluviatilis mosquitoes ( by its2 and 28s - d3 genes ) from india , iran , and other geographical areas by this genetic marker can bring more insight into taxonomy of this sibling species .\nthis study shows that coi gene can be used as a useful tool along other dna markers like 28-d3 gene for dissolving closely related taxa of an .\nfluviatilis mosquitoes ( by its2 and 28s - d3 genes ) from india , iran , and other geographical areas by this genetic marker can bring more insight into taxonomy of this sibling species .", "answer": "background : anopheles fluviatilis , one of the major malaria vectors in iran , is assumed to be a complex of sibling species . \n the aim of this study was to evaluate cytochrome oxidase i ( coi ) gene alongside 28s - d3 as a diagnostic tool for identification of an . \n fluviatilis sibling species in iran.methods:dna sample belonging to 24 an . \n fluviatilis mosquitoes from different geographical areas in south and southeastern iran were used for amplification of coi gene followed by sequencing . \n the 474475 bp coi sequences obtained in this study were aligned with 59 similar sequences of an . \n fluviatilis and a sequence of anopheles minimus , as out group , from genbank database . \n the distances between group and individual sequences were calculated and phylogenetic tree for obtained sequences was generated by using kimura two parameter ( k2p ) model of neighbor - joining method.results:phylogenetic analysis using coi gene grouped members of fars province ( central iran ) in two distinct clades separate from other iranian members representing hormozgan , kerman , and sistan va baluchestan provinces . \n the mean distance between iranian and indian individuals was 1.66% , whereas the value between fars province individuals and the group comprising individuals from other areas of iran was 2.06%.conclusion : presence of 2.06% mean distance between individuals from fars province and those from other areas of iran is indicative of at least two sibling species in an . \n fluviatilis mosquitoes of iran . \n this finding confirms earlier results based on rapd - pcr and 28s - d3 analysis .", "id": 934} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA three-component, Zn(OTf)2-mediated entry into trisubstituted 2-aminoimidazoles\n\nPaper sections:\n\nThis article is part of the thematic issue \"Multicomponent reactions III\".
\n\nIntroduction\nThe pioneering publications of Beller and co-workers describing Zn(OTf)2-catalyzed, microwave-promoted conversion of a mixture of a secondary propargylamide and an amine into a trisubstituted imidazole 1 [1\u20132] inspired us to explore several variants of this methodology. Last year, we described the synthesis of differently substituted imidazoles 2 from tertiary propargylamides and ammonium chloride under conventional heating [3]. More recently, we applied the Beller protocol to the synthesis of 2-substituted 5-methyloxazoles 3 from secondary propargylamides [4]. Being curious to explore more variants of N-carbonyl propargylamines, we turned our attention to propargylureas 4. These have been previously converted to the respective 2-imidazolones via base-promoted intramolecular amination of the propargyl group [5\u20136]. However, such transformations have not been studied under transition metal or Lewis acid catalysis. Moreover, the possibility to incorporate of an external primary amine into the cyclization process, which would lead to trisubstituted 2-aminoimidazoles 5 has not been explored (Figure 1). 2-Aminoimidazoles have a remarkably broad utility in medicinal chemistry [7]. Moreover, ureas 4 can, in principle, be generated in situ from the respective isocyanates and propargylamine (or propagyl isocyanate and primary amines), thus could offer an opportunity to synthesize 2-aminoimidazoles 5 in a three-component format. Considering these premises, we started to explore the Zn(OTf)2-catalyzed reaction of 4 with primary amines. Herein, we present the preliminary results of these studies.
\n\n\nExamples of imidazole (1 and 2) and oxazole (3) syntheses from propargylamides previously reported and the reaction of propargylureas 4 with primary amines studied in this work.
\n\nResults and Discussion\nUrea 4a (prepared by reacting propargylamine with 4-(trifluoromethoxy)benzyl isocyanate) was reacted with an equivalent amount of benzylamine in refluxing toluene in the presence of various Lewis acids. To our delight, the desired product 5a was observed and isolated in all cases involving Zn(OTf)2 catalysis. However, in contrast to previous reports on the preparation of related compounds [1\u20134], the reaction required substantial amounts (optimally, 50 mol %) of Zn(OTf)2 to achieve the best yield (76%). Notably, neither Sc(OTf)2 nor Cu(OTf)2 employed as catalysts produced a trace of the desired product. To rule out catalysis by adventitious TfOH, the reaction was performed in the presence of an equimolar amount of triflic acid, but no conversion could be detected (Table 1).
\n\n\nCatalyst screening results for the conversion of 4a to 5a.
\n\nResults and Discussion\nConsidering that in situ preparation of ureas 4 could, in principle, enable a three-component entry to imidazoles 5 (an attractive option from the standpoint of library array synthesis), we compared the isolated yield of the above reaction (with the ready-made urea 4a) with the yield obtained in the three-component format. To our delight, the three-component format led to only a slightly lower yield of 5a (62%). Viewing this as a worthy toll for the convenience of multicomponent chemistry, we proceeded investigating the scope of the newly established synthesis of trisubstituted 2-aminoimidazoles 5 (Figure 2).
\n\n\nSubstrate scope for the three-component synthesis of 5.
\n\nResults and Discussion\nAs it is evident from the data presented in Figure 2, the newly developed approach to the synthesis of medicinally important 2-imidazolines allows for independent variation of two periphery elements and provides generally good yields of the target compounds. The reaction can be performed with both, aromatic and aliphatic isocyanates. However, its scope is limited to aliphatic amines as the reaction failed to work for anilines (even electron-rich ones, such as p-anisidine). The tolerance of acid-labile protecting groups such as Boc is particularly useful as it offers an opportunity for further side-chain modifications.
From the mechanistic prospective, the reaction probably proceeds via Zn(OTf)2-catalyzed alkyne hydroamination followed by cyclodehydration as depicted in Figure 3, in full analogy with the previously proposed mechanism [2\u20133].
\n\n\nPlausible mechanism for the formation of 5.
\n\nConclusion\nIn summary, we have successfully employed propargylureas in the synthesis of trisubstituted 2-aminoimidazoles. This is the first example illustrating the utility of such ureas in the synthesis of imidazoles as previously reported syntheses only involved base-promoted cyclization into 2-imidazolones. The reaction can be conveniently conducted in a three-component format which makes it a useful tool for library array synthesis. The investigation of other metal-catalyzed transformations of propargylureas is underway in our laboratories and will be reported in due course.
\n\n\nGeneral experimental information, synthetic procedures, analytical data and NMR spectra for the reported compounds.
", "answer": "A three-component reaction involving in situ generation of propargylureas and subsequent Zn(OTf)2-mediated cyclocondensation with a primary amine yielded trisubstituted 2-aminoimidazoles. These findings are in contrast to the previously reported base-promoted unimolecular cyclization of propargylureas (leading to 2-imidazolones) and extend the range of Lewis acid-catalyzed azole syntheses based on N-carbonyl propargylamines.", "id": 935} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbenign neoplasms of the salivary glands are frequently encountered in dental practice . these account for 3% of the tumors involving the head and neck .\nthe majority of them occur in the parotid gland , and 80% of them are benign . of these benign neoplasms ,\n50 - 80% are pleomorphic adenomas and 5 - 20% are warthin 's tumors ( wt ) .\nhowever , warthin 's tumor is the most frequent monomorphic adenoma of the major salivary glands .\nthis is a curious benign neoplasm with its intimidating histological name , papillary cyst adenoma lymphomatosum .\nhowever , the eponym wt has been extensively used ever since aldred warthin reported two cases of this tumor in 1929 .\nearlier in the literature this was also referred to as adeno - lymphoma , papillary cyst adenoma , cystadeno - lymphoma , and epitheliolymphoid cyst .\nwt is generally a disease of elderly men , with the highest incidence in the sixth and seventh decades and the male : female ratio is 4.6:1 .\nthe typical features on cytology of wt include oncocytic cells in cohesive , monolayered sheets ; background lymphocytes ; and amorphous , cystic debris .\nhistopathologically , it has a cystic appearance with a double layer of oncocytes surrounding a lymphoid stroma .\nthe following case presentation deals with wt of the left parotid gland and highlights its clinicopathologic concepts along with its therapeutic management .\na 65-year - old male patient visited the department of oral medicine , with the chief complaint of swelling below the left ear lobe since six years .\npatient was a known smoker since the past 25 years and there was no history of alcohol consumption . on examination , the lesion extended from the left ear lobule to the lower border of the ramus of the mandible superoinferiorly and also extended behind the left ear [ figure 1 ] .\nit was approximately 5 cm in greatest dimensions ; smooth contoured , was firm in consistency and had well - defined borders .\nstimulation of the parotid glands yielded normal salivary flow with normal consistency , quantity and color .\nbased on the history and clinical examination , a provisional diagnosis of warthin 's tumor was given .\na differential diagnosis of pleomorphic adenoma , a low - grade parotid malignancy , lipoma and neurofibroma arising in the salivary gland were included .\nthe investigatory workup included complete hemogram , extra - oral radiograph , ultrasonography , computed tomography and excisional biopsy of the lesion .\nultrasonographic finding showed a well - defined hypoechoic mass in the lower pole of the left parotid gland .\nthe rest of the parotid gland parenchyma was normal and there was no evidence of ductal dilatation . computed tomography examination revealed a rounded and well - defined cystic lesion involving the superficial lobe of the left parotid gland [ figure 3 ] .\nultrasonograph showing well - defined hypoechoic mass computed tomography examination showing the lesion later , excisional biopsy of the lesion was planned using partial parotidectomy as the technique of choice [ figure 4 ] .\nthe tissue obtained was fixed in 10% of neutral buffered formalin , and processed routinely .\nthe sections stained with hematoxylin and eosin revealed cystic spaces lined by a papillary epithelial proliferation which was bilayered .\nthe cells of the epithelial lining appeared intensely eosinophilic . at the core of papillary projections\na variable amount of lymphoid tissue with mature lymphocytes was observed [ figure 5 ] .\ntumor after superficial parotidectomy microscopic picture ( 10 ) the patient did not present with any post - surgical complications .\nthe most accepted hypothesis about the origin of wt is that it develops from salivary duct inclusions in the lymph nodes , after the embryonic development of the parotid gland .\nthis hypothesis is further supported by the frequent detection of salivary gland tissue in the peri- and intraparotidal lymph nodes . in the parotid region , lymph nodes\nthe tumors presenting epithelial differentiations similar to those observed in wt develop outside lymph nodes and have no lymphoid stromal component .\nbenign tumors have only rarely been associated with cigarette smoking , which focuses attention on the nature of the underlying neoplastic process and how it may differ from other benign tumors .\nalthough generally believed to be an adenoma , wt , as suggested by allegra , may be a delayed hypersensitivity reaction .\nan interesting fact that caught the attention of the pathologists is that a decline in the incidence in men and a concurrent increased incidence in women has been observed in recent years .\nthe change is probably due to decline in the smoking habit in men and a reverse trend in women .\nthe increased frequency of adenolymphoma has been ascribed to the association of adenolymphoma with smoking and the proportional increase in female smokers .\nstudies conducted among atomic bomb survivors suggest that radiation may also be implicated in the tumorigenesis\nbarr virus ( ebv ) , because of the ebv dna found in tumor cells in some studies has not been substantiated .\nclinically , wt occurs almost exclusively in the parotid glands , in its superficial lobe and rarely in the deeper lobe ( 10% ) .\nthe other preferred locations include the buccal mucosa , submaxillary gland , lip and palate .\nthe patients can be asymptomatic or can have facial pain , rarely , facial nerve palsy may be seen in tumors associated with inflammation and fibrosis , which can be mistaken for malignant tumor .\nipsilateral earache , tinnitus and deafness are uncommon ear symptoms that might be seen in some patients .\nthe size is variable , from a few millimeters to centimeters , averaging 2 to 4 cm in diameter , with a preferred location in the lower pole of the gland ( in the jaw angle ) .\nit has been reported predominantly in whites , less frequently in orientals , and rarely in blacks .\nthe incidence rate is higher than that of salivary gland cancer but is lower than that of benign mixed tumors ( pleomorphic adenoma ) .\nmacroscopically wt presents as a spherical or ovoid mass , with a dense fibrous capsule and displaying multiple cystic compartments filled with a viscous yellow or dull brown material . however , eveson and cawson found 77% cases with an incomplete capsule , a full capsule in 8% and 16% tumors in which there was no evidence of capsule .\nthe cytological smears in our case showed variable amounts of cellularity , ranging from barely optimum cellularity to occasional hypercellularity .\nthere was an admixture of epithelial fragments , occasional single epithelial cells , and abundant lymphocytes noted in a granular cystic background .\nthe epithelial cells were oncocytic in appearance with large nuclei , prominent nucleoli , and moderately abundant granular cytoplasm .\nsince wt can be multifocal , a preoperative diagnosis by means of fine needle aspiration biopsy is mandatory and complete bilateral screening of the gland by mri is needed to program surgery .\n. an experienced cytopathologist can reliably distinguish malignant salivary pathologies from benign , but a histological classification based on only aspiration is an unrealistic goal .\ncomputerized tomography and magnetic resonance imaging enable accurate assessment of tumor extension , compression or infiltration of adjacent structures , presence of nodal metastases and better planning of the therapeutic approach .\ndynamic dual - phase scinti - scanning with technetium-99 , a recognized method of identifying adenolymphoma , could be used more frequently in these selected patient groups .\nlesion vascularity on initial power doppler examination is often relatively sparse , but wt that did contain areas of vascularity on initial examination showed a reduction in this vascularity as the tumor size reduced . with regard to luminal cells of the tumor lining the lymphoid stroma the cells reveal a similar aspect to the striated ducts of the normal salivary glands and have numerous mitochondria . these cells , called oxifile or oncocytic cells are swollen epithelial cells , with abundant eosinophilic granular cytoplasm , rich in mitochondria and enzymes .\nan increased number of oncocytic cells are also observed in the normal salivary glands once the person gets older .\nthe diffuse proliferation of the oncocytes without other changes has no pathologic significance and is called oncocytosis or oncocytic metaplasia .\nthe epithelial cells , the oncocytes , are disposed on two layers , a luminal layer of oncocytic columnar cells , supported by a discontinuous layer of oncocytic basal cells .\nthe nuclei of the luminal cells appear uniform and display palisading towards the free surface .\nthe basal cells possess round to oval nuclei , centrally located , small , with conspicuous nucleoli .\nthe lumen of the cysts contains thick proteinaceous secretions , cellular debris , cholesterol crystals , and sometimes , laminated bodies that resemble corpora amylacea .\nseifert recognizes four subtypes : subtype 1 ( classic wt ) is 50% epithelial ( 77% of all wt ) ; subtype 2 ( stroma - poor ) is 70 - 80% epithelial ( 14% cases ) ; subtype 3 ( stroma - rich ) is only 20 - 30% epithelial ( 2% ) ; and subtype 4 is characterized by extensive squamous metaplasia .\nhowever , presence of cellular atypia and a pseudoinfiltrative appearance of the metaplastic squamous epithelium in the residual tumor often can be mistaken for squamous cell or mucoepidermoid carcinoma .\nsquamous metaplasia of wt usually lacks keratinization , which is seen in most squamous cell carcinoma .\nin contrast to low - grade mucoepidermoid carcinoma , there is no definite infiltrative growth and the tumor cells appear more frankly squamous .\na differential diagnosis must be made also with a variant of papillary thyroid carcinoma recently reported as warthin - like .\nthe microscopic characteristic is a prominent lymphoid stroma and oncocytic metaplasia of the epithelium , but the nuclei have chromatin clearing , inclusion and groove - formation and the epithelial cells show immunohistochemical expression of thyroglobulin .\nthe differential diagnosis of this malignancy should be performed preferably with pleomorphic adenoma and cystoadenoma .\nthe anatomico - pathological diagnosis is generally easy , but it also should be distinguished from canalicular adenoma , sialadenoma as well as from branchial cyst when involving the parotid gland .\nsunardhi - widyaputra and van darmne in 1993 immunohistochemically studied the presence of tenacin , a molecule in the mesenchyme of salivary glands believed to play a role in the embryogenesis and development of tumors , in papillary cystadenoma lymphomatosum and in oncocytoma .\nthey found the protein to be abundant in papillary cystadenoma lymphomatosum , prominent in the proximity of the basement membrane , beneath the oncocytic epithelial components .\ntenacin staining in oncocytoma was focal although oncocytes are the actively proliferating cells in this tumor .\nthe presence of oncocytic myoepithelial cells both in papillary cystadenoma lymphomatosum and in oncocytoma surrounded by tenacin suggested that both tumors may arise from stem cells that are capable of differentiating into aberrant epithelial cells ( oncocytes ) , myoepithelial cells in variable proportion or both .\nrecent molecular studies have shown that the epithelial component is polyclonal and does not exhibit clonal allelic losses , suggesting that this tumor is not a true neoplasm .\nrecent studies have also reported the presence of b - cells ( cd20 ) , nk ( cd56 ) and t ( cd3 ) , including helper subtypes ( cd4 ) and suppressor ( cd8 ) in the tumor 's stroma , something similar to that of normal or reactive lymph nodes . also , it was found that cd20-positive b - lymphocytes were located in the germ centers and peripheral b - area while cd3-positive t - lymphocytes are located interfollicularly .\nsurgeons are traditionalists , and the early experience of our peers has colored current surgical opinion and slowed the introduction of conservative surgery for the benign parotid lump .\nthis situation is now changing , and centers with experience of treating parotid tumors increasingly recognize that benign tumors can be removed safely by techniques much less invasive than a formal parotidectomy .\nthis surgical modality is based on meticulous dissection immediately outside the tumor capsule with preservation of the facial nerves .\nin view of the possible association of wt with extra - salivary neoplasms , extensive workup of the patients harboring multiple wt is , therefore , indicated and long - term follow - up is mandatory , due to the possible occurrence of metachronous salivary and extra - salivary tumors even after prolonged time intervals .\nrarely , either the epithelial or lymphoid component of wt can undergo malignant transformation with an estimated incidence of less than 0.1% . in order of frequency ,\nthe commonest carcinomas are squamous cell carcinoma , oncocytic carcinoma , adenocarcinoma , undifferentiated carcinoma , mucoepidermoid carcinoma and merkel cell carcinoma .\ncomplications must be unusual and of low frequency for the surgical resection of a wt , including some complications considered of minor importance , such as paresis of the ear lobe resulting from manipulation and/or section of the auricularis magnus branch of the superficial cervical plexus .\nthe auricularis magnus nerve , in its path toward the ear lobe , may pass through the tumor , hampering the dissection .\nanother complication of lesser importance is the change of facial contour due to resection of a large portion of the parotid gland .", "answer": "warthin 's tumor undoubtedly is the most frequent monomorphic adenoma of the major salivary glands . \n clinically , it appears as a slow - growing tumor often fluctuant on palpation due to its cystic nature . \n the treatment of choice is complete excision with wide tumor - free margins . \n this article highlights a case of warthin 's tumor of the parotid gland in an elderly male patient along with a review of the literature on the aforementioned pathology .", "id": 936} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthyroid cancer is the most common type of cancer in korea , with differentiated thyroid cancer ( dtc , includes papillary and follicular thyroid cancer ) accounting for the vast majority of cases .\nthe standard treatment for dtc is thyroidectomy followed by i ( radioactive iodine , rai ) therapy and thyroxine suppression to decrease serum thyroid stimulating hormone ( tsh ) .\nrai therapy eliminates microscopic residual tissues after thyroidectomy which decreases the likelihood of thyroid cancer recurrence .\nprior to rai therapy , the patient is advised to maintain a low - iodine diet ( lid ) to facilitate i uptake , maximizing the efficiency of rai therapy .\nappropriate levels of dietary iodine intake or duration of the lid are not yet standardized over regions or countries .\nthe american thyroid association recommends the lid with less than 50 g / day of dietary iodine for 1 - 2 weeks prior to rai therapy , but the korean thyroid association recommends a low - iodine diet with less than 100 g / day and provide a dietary guideline for the lid where allowed or restricted food items are listed during the lid . in iodine - rich areas such as korea , the recommended level of iodine intake during the lid is important to facilitate maintaining the lid , because a strict guideline may negatively impact the lid compliance .\na few studies were reported results of less strict diet or short periods of the lid , however , the general consensus among clinical dietitians in korea regarding appropriate degree or duration of the lid have not yet elucidated . according to moon\net al . , clinical dietitians should develop a practical dietary strategy in order to improve and facilitate the lid compliance . to improve the compliance of the lid\nmost previous studies used urinary iodine measurements due to the lack of an iodine database and the difficulties in dietary survey .\nurinary iodine excretion is a good measure for dietary iodine intake , but evaluating the dietary iodine intake using multiple days of dietary records would provide a more comprehensive measure of dietary iodine intake in order to develop a practical dietary strategy for the lid . therefore , this study aims to assess dietary iodine level using three - day of dietary records and to search food sources that cause low adherence to the lid .\nin addition , we attempted to evaluate the ablation rate of remnant thyroid by compliance of the lid .\nwe experienced three patients showing the diet composing iodine levels over 100 g / day despite their efforts for the lid before initial rai therapy .\nthe protocol of case report was approved by the institutional review board of college of medicine at seoul national university ( h-1308 - 066 - 513 ) , and all the patients provided their written informed consent to participate .\nthe patients had stage ii or iii papillary thyroid cancer , classified based on the cancer staging manual in the 7 edition of the american joint committee on cancer ( ajcc ) .\nall three patients were educated on the preparation and management of the lid prior to rai therapy in a two - and - a - half - hour intensive education session . during the session ,\na clinical dietitian explained patients of the importance and methodology of maintaining the lid in a half - hour .\nthen the patients maintained the lid for two weeks prior to i administration ( 1.1 gbq ) and a whole body scan ( wbs ) , which was done three days after the i administration . to elevate their tsh levels , recombinant human tsh ( rhtsh ; thyrogen , genzyme , cambridge , ma , usa )\ndietary intakes for patients were assessed using three - day dietary records during usual diet period and the lid period respectively .\npatients were taught how to record their diet and asked to record three - day dietary records at two weekdays and one weekend day .\nenergy and nutrient intakes , except for iodine , were calculated using a diet evaluation system ( des ) .\niodine intake was estimated using the database recently established by han et al . and modified for this study .\nsuccessful remnant ablation is defined as an absence of visible rai uptake on a subsequent diagnostic rai scan or an undetectable stimulated serum thyroglobulin ( off - tg ) level .\nfigure 1 presents the dietary iodine intake in both the usual diet and lid periods .\nalthough the patients tried to maintain their lid according to the guideline of less than 100 g / day their mean daily iodine intakes during two - week lid period were more than 100 g .\nfor patient 1 , the mean iodine intake level for usual diet and the lid were 317.2 and 117.0 g / day respectively .\npatient 2 's levels were 125.2 and 110.9 g / day and patient 3 's levels were 217.7 and 100.4 g / day .\nthe values in all three patients were reduced after a two - week lid period , but the iodine / creatinine ratio in spot urine exceeded 66.2 g / g ( iodide / creatinine ) , that was the cutoff value for a poorly maintained lid set by kim et al . .\nall three patients followed five items out of nine food items in the lid guidelines that were using refined salts instead of sea salts and avoiding seaweeds , egg yolk , processed food , and consumed adequate amount of meat and its product , which was less than 120 g / day .\npatient 1 and patient 3 also followed three more items that were avoiding fish , milk and dairy products consumption , soybean pastes and soy sauce made with sea salts .\npatient 2 , however , did not follow three items and consumed fish , milk and dairy products , condiments including sea salts .\nthe food item in the guideline that all three patients did not follow was avoiding salted vegetables , mainly kimchi during the lid .\npatient 2 showed the lowest adherence to the lid and the mean iodine intake level during the lid periods was not much different from patient 2 's usual intake level .\nthough serum off - tg levels became undetectable ( < 1.0 ng / ml ) for patients 1 and 2 , patient 3 's off - tg level was 1.07 ng / ml and all three patients showed visible rai uptake .\nwe evaluated dietary iodine during lid and successful ablation of the rai therapy for three differentiated thyroid cancer patients .\nall three patients showed low adherence to the lid guideline , in particular for salted vegetable and exhibited remnant thyroid activity in the second post - rai therapy scan .\ndietary assessment of iodine intake is challenging because the large day - to - day variation makes it difficult to quantify the \" usual \" iodine intake .\nhowever , the dietary iodine intakes are comparable with the previous findings where dietary iodine intake was reported 478 g / day for korean healthy adults using food frequency questionnaire and 312 g / day in men and 413 g / day in women for japanese using 7-day dietary records . in besides\n, we measured urinary iodide excretion in both usual diet and the lid periods along with dietary iodine and both two values showed the same trend of being markedly reduced . although our patients were intensively educated on maintaining the lid , all of their dietary iodine intake levels exceeded the less than 100 g guideline set by the kta .\npatient 2 did not follow the lid guidelines such as avoiding dairy , fish and kimchi .\npatients 1 and 3 followed kta guidelines except for the restriction on kimchi . maintaining the lid is challenging for korean patients , whose regular diet consists of foods with very high iodine content , such as seaweeds , seafoods , soy sauce , soy bean pastes , and salted vegetables such as kimchi . according to moon et al . , thyroid cancer patients had considerable knowledge of high iodine content foods but they had a difficulty to prepare low iodine dishes not using sea salts . though seaweed has the highest iodine content and is by far the biggest contributor to dietary iodine consumption , the patients ' main source of iodine was kimchi during the lid period .\nkimchi is a main side dish in our korean diet and is usually made of large amounts of sea salts , garlic , red pepper , salted fish and other spices . according to analytical values determined by the korean food and drug administration ( kfda ) , the iodine content per 100 g of radish kimchi , napa cabbage kimchi , and young radish kimchi are 198.4 , 143.4 , and 107.4 g respectively .\ntherefore , avoiding foods with a high sea salts content , such as kimchi , is very important for successful rai therapy .\nalthough clinical dietitian put enough emphasis on avoiding sea salts or replacing sea salts with refined salts , it is very challenging for patients to distinguish the dishes made by refined salts from all dishes or to prepare their own dishes with refined salts in daily life . to increase the adherence of the lid , more practical dietary strategy for avoiding sea salts or for replacing sea salts in our korean dishes\nlow adherence to the lid guideline with more than 100 g / d of dietary iodine intake level negatively influenced the efficacy of rai therapy .\nfuture studies are required to explore the influence of various dietary iodine intake levels on the efficacy of rai therapy and to develop more practical guidelines to facilitate the lid maintenance .", "answer": "to improve the efficacy of radioactive iodine ( rai ) therapy for differentiated thyroid cancer patients , a low - iodine diet ( lid ) prior to the therapy is recommended . in iodine - rich areas such as korea , however , a strict lid is very difficult to maintain . \n we experienced the cases of three patients showing low adherence to the lid before initial rai therapy , and analyzed the main food source supplying iodine during the lid , and examined the influence of the poorly maintained lid on the efficacy of rai therapy . \n the dietary intake during the lid periods were assessed using three - day dietary records and remnant thyroid activity after the second rai administration was also evaluated . \n all patients ' mean daily iodine intake during two - week lid periods exceeded the 100 g guideline set by the korean thyroid association ( median 110.9 g , ranges 100.4 - 117.0 g ) . \n although the typical food sources of iodine intake are seaweeds in korea , salted vegetables were the main contributor to the patients ' iodine intake during the lid periods . \n remnant thyroid activity was shown on a follow - up scan in all of 3 patients suggesting low efficacy of rai therapy . in summary , \n the patients with low adherence to the lid guideline showed unsuccessful remnant ablation , and the main food source of iodine was salted vegetables . \n further studies are necessary to examine the relationship between adherence of the lid and rai efficacy according to dietary iodine intake levels , as well as food sources that cause low adherence to the lid . \n these data can then be used to develop more practical lid guidelines .", "id": 937} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na lymphoepithelioma - like carcinoma ( lelc ) is a tumor which mimics lymphoepithelioma in terms of its pathological features .\nthe primary lesion of lelc occurs in the stomach , lungs , thymus , salivary glands or urinary bladder .\nlelc of the urinary bladder ( lelcb ) is a rare variant of infiltrating urothelial carcinoma and was first described by zukerberg et al . in 1991 .\nincluding this case , there are merely 105 cases in the english language medical literature , with only 8 cases reported as originating from asian countries [ 3 , 4 , 5 , 6 ] . in 1994 , amin et al . \npure ( 100% ) , predominant ( 5099% ) and focal ( < 50% ) , with the three types determining a patient 's prognosis .\nwe herein report a case of lelcb , with a preoperative diagnosis of an undifferentiated carcinoma , in which radical cystectomy and systemic chemotherapy were successfully undertaken .\nbased on previous case reports of lelcb in the english language medical literature , we examined the prognosis for lelcb .\nin addition , we analyzed the preoperative diagnostic characteristics of this lelcb by measuring its apparent diffusion coefficient ( adc ) value by magnetic resonance imaging ( mri ) and compared this to those of past cases of urothelial carcinoma of the urinary bladder at our institution .\non cystoscopy , two bladder tumors were observed , one on the left side of the trigone and the other on the right side of the trigone .\na total body computed tomography ( ct ) scan was performed and the presence of distant metastases or lymph node involvement was excluded .\nmri revealed that the tumor on the left side of the trigone had invaded the perivesical soft tissue of the bladder , but not the prostate or seminal vesicles ( fig .\npathological findings revealed undifferentiated atypical epithelial cells with enlarged nuclei that had formed into sheets to invade the muscle layer .\npathological findings revealed large , undifferentiated carcinoma cells with pleomorphic nuclei and prominent nucleoli , the infiltration of inflammatory cells consisting predominantly of lymphocytes , and the reach of their invasion to the perivesical soft tissue of the bladder ( fig .\nthe final pathological diagnosis was an invasive urothelial carcinoma , lymphoepithelioma - like variant , pt3 .\ntumor cells were positive for cytokeratin ( ae1/ae3 ) ( fig . 2c ) and e - cadherin ( fig .\n, cisplatin - based systemic chemotherapy was performed , and cancer recurrence was not apparent at the usual follow - up as determined by ct scan and cytological analysis .\naccording to the who classification criteria , lelcb is defined as a subtype of undifferentiated carcinomas .\nto date 105 cases , including this one , have been described in the english language medical literature .\nlelcb shows carcinomatous components contrasting with lymphocyte infiltration and mimics chronic inflammation or malignant lymphoma ; immunohistochemical stains such as for cytokeratin are helpful in distinguishing between these diseases [ 6 , 7 ] . between 1991 and june 2015 , 84 cases of lelcb , according to the classification of amin et al .\nwe allocated the 84 cases to two groups pure / predominant and focal and investigated their prognoses based on previous reports .\nseventy patients ( 83% ) formed the pure / predominant group and 14 patients ( 17% ) formed the focal group .\nkaplan - meier curves of overall survival rates of the pure / predominant and focal groups are shown in figure 3 . as a result ,\nthe pure / predominant group had as significantly better prognosis than the focal type group ( log - rank test , p < 0.001 ) ( fig .\nthe predominant or focal types of lelcb include squamous cell carcinoma , adenocarcinoma and urothelial carcinoma .\ncontaining only lelc , this case seemed to have the characteristics of a pure type of lelcb .\nunfortunately , there is at present no established treatment for lelcb because of its rarity as a bladder tumor subtype , with few reports existing for this disease .\nsome reports describe lelcb as being sensitive to cisplatin , while others suggest that it is possible to preserve the bladder in the case of a pure or predominant type , even if the tumor has invaded the muscle [ 4 , 8 , 9 , 10 ] .\nadjuvant cisplatin - based chemotherapy was also instituted because radical cystectomy yielded a diagnosis of lelcb pt3 .\nthe combination of external beam radiotherapy and chemotherapy to preserve the bladder may be considered a suitable treatment option if the diagnosis prior to radical cystectomy is accurate .\nepstein - barr virus ( ebv ) is associated with lymphoepithelioma or lelc of several tissues ( lung , stomach and salivary glands ) , except the bladder .\na close reading of the literature suggests that if tumor cells are positive for ebv rna , the tumor might be a metastasis from another tissue .\ntherefore , we performed ebv - encoded small rna in situ hybridization ( eber - ish ) , but this did not reveal a relationship between ebv and lelcb in this case ( fig .\nhowever , in treating lelcb , eber - ish is useful and necessary to rule out the tumor as being a metastasis from another tissue .\nmri is widely used in local staging or to detect lymph node metastases , and is essential for determining suitable treatments for bladder tumors . recently ,\nmeasuring adc values has been suggested to be helpful in diagnosing bladder tumors . to further improve preoperative diagnostic accuracy , we retrospectively measured the adc value of this case .\nthe mean value was found to be 782 10 mm / s ( fig .\n1c ) , which was relatively lower than the mean values we found for muscle - invading urothelial carcinomas studied at our institution ( 56 cases , median 1,047 10 mm / s ; see online suppl .\nmaterial , www.karger.com/doi/10.1159/000445049 ) . in urothelial carcinoma , in 2014 yamada et al . reported a correlation between high adc values and good histopathological features of bladder tumors which is the case for urothelial carcinoma .\nhowever , in spite of the relatively low adc value , the prognosis of this case was relatively good as previously described\n. the low adc value calculated in this case may be due to the fact that the observed lymphocyte infiltration probably caused an increase in cell density and a decrease in diffusion capacity .\nthere are several pitfalls and limitations in detecting pathological characteristics of tumors , and further consideration will have to be given to the usefulness of measuring adc values of bladder tumors .\nregardless , though lelcb is a rare tumor , measuring adc values may be useful in predicting the histopathological characteristics of such bladder tumors .\nwe treated a rare case of lelcb , classed as a pure type and with a better prognosis than the focal type according to the classification of amin et al . .\nit is necessary to consider a diagnosis of lelcb when turbt indicates an undifferentiated carcinoma .\nadditionally , measuring the adc value of a urinary bladder tumor may be helpful in predicting its pathological features .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\na copy of the written consent is available for review from the editor - in - chief of this journal .\nthe authors received no financial support for the research , authorship and/or publication of this paper .", "answer": "lymphoepithelioma - like carcinoma of the urinary bladder ( lelcb ) is a rare variant of infiltrating urothelial carcinoma . \n we report a case of lelcb in a 43-year - old man . \n ultrasonography and cystoscopy revealed two bladder tumors , one on the left side of the trigone and the other on the right side of the trigone . \n transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma . \n we therefore performed radical cystectomy and urinary diversion . \n immunohistochemically the tumor cells were positive for cytokeratin , but negative for epstein - barr virus - encoded small rna in situ hybridization as found for previous cases of lelcb . \n the final pathological diagnosis was a lymphoepithelioma - like variant of urothelial carcinoma with perivesical soft tissue invasion . \n for adjuvant systemic chemotherapy , three courses of cisplatin were administered . \n the patient subsequently became free of cancer 72 months postoperatively . \n based on the literature , pure or predominant lelcb types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy . \n an analysis of the apparent diffusion coefficient ( adc ) values of bladder tumors examined in our institution revealed that the adc value measured for this lelcb was relatively low compared to conventional urothelial carcinomas . \n this suggests that measuring the adc value of a lymphoepithelioma - like carcinoma prior to operation may be helpful in predicting lelcb .", "id": 938} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nelectroconvulsive therapy ( ect ) is a strong option for treating patients with medication - resistant depression , a high risk of suicide , psychotic agitation , and other severe mental issues .\nhowever , gaines and rees1 suggested that ect increases cerebral blood flow 1.5-fold to sevenfold and raises intracranial pressure .\nthese effects may increase the risk of intracranial hemorrhage , especially in patients with a brain tumor , an intracranial vascular abnormality , or hemorrhagic disease .\nhemophilia , a hemorrhagic disease , is usually an x - linked recessive disorder induced by a deficiency of factor viii ( hemophilia a ) or factor ix ( hemophilia b ) .\nhemophilia a is the usual form of the disorder , and occurs in about one out of every 5,00010,000 male births .\nthe number of patients with hemophilia b is about one - fifth that of hemophilia a. globally , the number of patients with hemophilia is estimated at about 400,000 .\nalthough the incidence of hemophilia is low , it is possible that schizophrenia requiring ect could co - occur with hemophilia .\nhowever , only one paper reports a demonstration of the safe usage of ect in a patient with hemophilia.2 herein , we describe a second case of successful ect for medication - resistant schizophrenia in a patient with severe hemophilia a. a 26-year - old japanese man had been treated for severe hemophilia a ( severe , coagulation factor viii activity < 1 % ; moderate , 1%5% ; mild , 5%40% ) . he was admitted to a mental hospital for auditory hallucinations , a persecution complex , world destruction fantasies , and psychomotor excitation , and was diagnosed with schizophrenia by diagnostic and statistical manual of mental disorders , fourth edition , text revision criteria .\n. then haloperidol ( 12 mg / day ) was combined with olanzapine instead of risperidone .\nthis antipsychotic combination therapy ( olanzapine 20 mg / day plus haloperidol 12 mg / day ) was partly effective against the auditory hallucinations , but the patient s psychiatric state immediately deteriorated thereafter and suicidal ideation emerged .\nin addition , his bleeding tendency worsened and multiple subcutaneous hematomas appeared on his body . because clozapine had not been approved in our province at that time and ect has immediate and strong effects on schizophrenic symptoms including suicidal ideation,3 the patient\nwas transferred to our general hospital for the management of hemophilia a and for ect . after consulting with hematologists ,\nect was performed after the patient had been supplemented with coagulation factor viii to prevent intracranial and systematic hemorrhage .\nwe administered factor viii concentrates ( 1,000 iu ; kogenate fs , bayer healthcare pharmaceuticals inc . ,\nthe dose of kogenate fs was determined to keep factor viii activity at 30%40% during ect .\nthe factor viii activity target range was recommended by hematologists based on the report by glaub et al.2 since the patient s mental state was impaired , written informed consent for the procedure was obtained from the patient s family .\nbitemporal ect was administered two or three times a week . a thymatron stimulation device ( somatics ,\nlake bluff , il , usa ) was used for ect ; the stimulation conditions were 0.5 ms pulses , 40 hz , 0.9 a , and 252 mc .\nafter a course of eight ect sessions , his world destruction fantasies , psychomotor excitation , and suicidal ideation were improved . however , since his auditory hallucinations and persecution complex persisted , a second course of eight treatment sessions was administered , which ameliorated the remaining psychiatric symptoms .\nafter the 16th ect session , brain mri was performed to determine whether organic brain disease was present , and there was no sign of brain disease or bleeding .\na 26-year - old japanese man had been treated for severe hemophilia a ( severe , coagulation factor viii activity < 1 % ; moderate , 1%5% ; mild , 5%40% ) .\nhe was admitted to a mental hospital for auditory hallucinations , a persecution complex , world destruction fantasies , and psychomotor excitation , and was diagnosed with schizophrenia by diagnostic and statistical manual of mental disorders , fourth edition , text revision criteria .\nhowever , the auditory hallucinations , persecution complex , and psychomotor excitation persisted . then haloperidol ( 12 mg / day )\nwas combined with olanzapine instead of risperidone . this antipsychotic combination therapy ( olanzapine 20 mg / day plus haloperidol 12 mg / day )\nwas partly effective against the auditory hallucinations , but the patient s psychiatric state immediately deteriorated thereafter and suicidal ideation emerged .\nin addition , his bleeding tendency worsened and multiple subcutaneous hematomas appeared on his body . because clozapine had not been approved in our province at that time and ect has immediate and strong effects on schizophrenic symptoms including suicidal ideation,3 the patient\nwas transferred to our general hospital for the management of hemophilia a and for ect . after consulting with hematologists ,\nect was performed after the patient had been supplemented with coagulation factor viii to prevent intracranial and systematic hemorrhage .\nwe administered factor viii concentrates ( 1,000 iu ; kogenate fs , bayer healthcare pharmaceuticals inc . ,\nthe dose of kogenate fs was determined to keep factor viii activity at 30%40% during ect .\nthe factor viii activity target range was recommended by hematologists based on the report by glaub et al.2 since the patient s mental state was impaired , written informed consent for the procedure was obtained from the patient s family .\nbitemporal ect was administered two or three times a week . a thymatron stimulation device ( somatics , lake bluff , il , usa ) was used for ect ;\nthe stimulation conditions were 0.5 ms pulses , 40 hz , 0.9 a , and 252 mc .\nafter a course of eight ect sessions , his world destruction fantasies , psychomotor excitation , and suicidal ideation were improved . however , since his auditory hallucinations and persecution complex persisted , a second course of eight treatment sessions was administered , which ameliorated the remaining psychiatric symptoms .\nafter the 16th ect session , brain mri was performed to determine whether organic brain disease was present , and there was no sign of brain disease or bleeding .\na task force report of the american psychiatric association ( apa)4 has suggested that there are no absolute contraindications to ect , but that recent stroke , cerebrovascular malformations , and space - occupying intracranial lesions are related to an increased risk of intracranial hemorrhage due to ect .\nthis apa statement may have discouraged psychiatrists from performing ect on patients with bleeding tendencies such as in hemophilia .\nmehta et al5 reported the results of a study of 35 patients receiving warfarin , an anticoagulant inhibiting the synthesis of vitamin k - dependent clotting factors such as factors ii , vii , ix , and x. the extrinsic clotting system is impaired in patients with hemophilia a , and warfarin extends the intrinsic and extrinsic clotting systems . in the study , international normalized ratio values measured on the day of ect varied notably , including subtherapeutic , therapeutic , and supratherapeutic .\nglaub et al2 demonstrated that ect could be performed without bleeding or other complications when patients with hemophilia a were pre - treated with factor viii concentrates .\nour report shows the safety of ect for patients with hemophilia a when they are supplemented with coagulation factor viii .\npatients with hemophilia can even undergo open surgery6 with appropriate management of the condition with coagulation factors .\nthus , although only two patients with hemophilia a have successfully received ect , evidence suggests that patients with hemophilia can be safely treated with ect if pretreated with factor viii . in conclusion ,\nwhen a patient with hemophilia a is pre - treated with factor viii , ect may be performed safely . for patients with hemophilia", "answer": "electroconvulsive therapy ( ect ) is used for medication - resistant and life - threatening mental disorders , and therefore it occupies an important position in psychiatric treatment . \n ect reportedly increases intracranial pressure and is suspected of increasing the risk of intracranial hemorrhage , especially in patients with hemorrhagic diseases such as hemophilia . \n a decrease in or loss of blood coagulation factors , including factor viii and factor ix , are found in hemophilia a and b , respectively . \n psychiatrists may hesitate to perform ect on patients with bleeding tendencies , such as in hemophilia . here , we report the successful use of ect on a neuroleptic - resistant patient with schizophrenia and severe hemophilia a. we performed ect 16 times supplemented with coagulation factor viii to prevent intracranial and systematic hemorrhage . we administered factor \n viii concentrates to the patient to keep factor viii activity at 30%40% during ect . \n the patient did not show bleeding or other complications during the ect sessions . \n we suggest that pretreatment with factor viii can help manage the increased risks of intracranial and systematic bleeding during ect that is present in patients with hemophilia a. the present report supports the idea of performing ect safely on patients with hemophilia a by administering factor viii .", "id": 939} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nalthough great enthusiasm exists for developing skills in laparoscopic urology in the united kingdom , training opportunities are limited .\nthis is primarily due to a lack of approved urology / laparoscopy fellowships , as exist in the united states .\nit is an unfortunate fact that many interested urologists do not progress beyond the initial courses stage and indeed a number of urologists who have attended animal laboratory training as well have not proceeded to regular urological laparoscopic practice .\nfellowship , enabling supervised training so that interested urologists could become comfortable and competent with laparoscopic urology .\nthe fellowship program is available to those who have completed the 2 initial training steps , ie , basic / advanced training courses and an animal laboratory course .\nprior practice on simulators using laparoscopic instruments is encouraged to enable the trainees to get the most out of their time spent with the mentor in the clinical setting .\nbasic training is centered on the development of familiarity with the safe handling of laparoscopic instrumentation and stereoscopic skills in the dry laboratory setting .\nadvanced training involves a series of formal lectures followed by practice sessions in the animal laboratory ; attendees are also shown live surgery via video links .\nskills training is assessed by the mentor in these phases by objectively marking the achievement of various predetermined parameters that evaluate safe acquisition of laparoscopic skills like clipping and suturing .\nthe fellowship program steps are broadly similar thereafter , but individual variations may occur , depending on the distance that the trainee has to travel and availability of the mentor .\nan honorary contract is raised for the trainee at the mentor hospital ; the trainee then observes the mentor perform 4 or 5 laparoscopic renal procedures and may assist with the same by acting as the camera driver for these cases .\nif possible , trainees then refer cases suitable for laparoscopic surgery to the mentor ; this helps gestate the necessary workload .\nthe first 4 cases that are performed by the trainee are usually hand - assisted simple or radical nephrectomies , and the aim is to perform at least a case a week at a dedicated theater session with the possibility of adding in more cases as appropriate .\nthe trainee then goes on to perform conventional laparoscopic cases , again under mentor supervision , with the mentor initially acting as camera driver .\nthis program duration varies but is approximately 4 to 5 months , primarily due to the paucity of clinical material available in any one unit at a time , and secondly , to fit in with other work commitments .\nmentors are then awarded an honorary contract at the trainees ' hospital to supervise the trainees during their first few cases therein .\ntrainees schedule simple cases initially and gradually increase the level of difficulty as their skills and confidence improve .\nsix of them are in independent laparoscopic urological practice , and the others are in phase 6 or above .\ntrainee one started this program in september 2000 and observed 4 simple nephrectomies and 1 radical nephrectomy before proceeding to phase 6 .\nbecause of the distance involved , the mentor condensed stages 4 and 5 and performed 12 cases with the trainee at the trainee 's hospital before the trainee entered independent practice . since then , he has performed 14 unsupervised laparoscopic urological procedures .\ntrainee two started the program in may 2001 and has performed 10 procedures with the mentor ; he was fortunate to obtain further hands - on training abroad , which helped shorten his training .\ntrainee three , four , five , and six started the program in may 2002 and performed 10 procedures each with the mentor , before commencing unsupervised practice .\ntrainees seven , eight , and nine are making steady progress , currently performing hand - assisted procedures with the mentor who is offering support and advice without actually being scrubbed in for the procedure .\nit is anticipated that over the next few months trainees seven , eight , and nine will adopt independent practice .\nskills development in all cases was steady , with a progressive increase in dexterity and improvement in spatial orientation .\nfor the neophyte laparoscopist , it is indeed a great leap of faith that has to be taken from the animal laboratory to the human arena ; we perceive the main stumbling block to be a lack of direct mentor / trainee supervision .\nthis program was designed to allow skill and confidence building under the direct supervision and guidance of experienced laparoscopic urologists , as initially suggested by shalhav . in effect , this reduces the conversion rate and complications that otherwise could be a major issue ; therefore , the transition to independent urological practice appears to be smoother .\nwe also believe that the selective use of hand assistance early in the program helps build confidence and aids in development of 3-dimensional spatial orientation ; secondly , the ability to directly apply digital pressure exists in case of unexpected vascular injury .\nonce trainees are facile with hand - assisted laparoscopic practice , they are then encouraged to move on towards pure laparoscopic and retroperitoneoscopic procedures ; all trainees agreed that the initial phase helped them make the transition more easily .\nthe case load at one particular hospital may not be enough to enable concentrated dissemination of laparoscopic skills . as a result ,\nsometimes trainees have had to spend up to 4 weeks on occasion without performing a single laparoscopic case ; this in turn has a bearing on the length of the fellowship program .\nit is not easy to put a finite number onto the number of mentored cases that would have to be performed by trainees before proceeding to independent practice because this appears to depend on innate skills , but 10 cases would seem to approximate an acceptable mean .\nsome trainees have had to forfeit other obligations for the duration of the fellowship , which they could not have done without support from their colleagues and the management in their respective hospitals .\nwe acknowledge unstinting support from anaesthetic colleagues , given the fact that anaesthetic / procedure time needs to be acceptable ; this has obviously not always been the case when a new trainee joins the fellowship program .\nthis program seeks to help safely relocate the teaching of laparoscopy from the lecture hall and animal laboratory to the clinical setting , and , in doing so , we hope to accelerate the training of interested , qualified urologists over the next few years . residents and fellows are being trained in laparoscopic urology now ; as a result , this fellowship may be phased out in the future ; until this noticeable lacuna in training is filled , we would wish to continue to offer this training to interested consultant urologists .\na one - on - one fellowship program enables rapid , safe , and effective laparoscopic skills acquisition by established urologists .", "answer": "objectives : a fellowship training model in laparoscopic urological surgery has been established for interested urologists to help them proceed from the pelvic trainer/ animal laboratory environment to safe clinical practice . \n the objective of the model is to provide trainees with clinical experience under direct mentor supervision before embarking on independent laparoscopic urological surgery at their own base hospitals.methods:the fellowship model incorporates 9 fluid phases : phase 1 to complete basic and advanced training courses . \n phase 2 to practice at home or in the office using pelvic trainers . \n phase 3 to proceed to an animal laboratory course . \n phase 4 to visit centers of international repute to observe high - volume laparoscopic urology . \n phase 5 to observe the mentor perform several major renal laparoscopic cases . \n phase 6 to perform several hand - assisted renal procedures under direct mentor guidance at the mentor hospital . \n phase 7 to perform several laparoscopic or retroperitoneoscopic renal procedures , or both , under direct mentor guidance at the mentor hospital . \n phase 8 to mentor assisted trainees to start laparoscopic surgery at their own hospitals . \n phase 9 to practice laparoscopic urology independently.results:so far , 9 trainees have participated in the fellowship . \n six have reached phase 9 with independent practice , 2 others are in phase 8 , and 1 is in phase 7 . \n skills development has been steady , with progressive acquisition of surgical dexterity and spatial orientation.conclusion:this fluid fellowship model provides urologists with clinically applicable teaching experience to learn a relatively new surgical concept safely and effectively , thereby promoting clinical governance . it may be possible for other centers to establish similar fluid mini fellowships to help disseminate laparoscopic surgical skills .", "id": 940} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nventriculoperitoneal ( vp ) shunting is commonly utilized as a diversion procedure for patients with hydrocephalus .\nmultiple techniques for initial placement of the catheters have been described , including conventional minilaparotomy , peel - away introducer sheaths , as well as full laparoscopic approaches .\nvp shunts fail for a variety of reasons , including failure secondary to disconnection of abdominal tubing with migration of the tubing , most commonly further into the peritoneal cavity ; this occurs in 2.5% to 4% of shunts placed according to current published series .\ninitial shunt failure rates continue to be high , with a reported failure rate of 31% at 6 months and an infection rate of 7% .\ncommon presenting features of shunt failure include headache , mental status changes , and vomiting .\nlaparoscopy avoids laparotomy and may provide improved confirmation of shunt functionality and placement at the time of revision .\na 31-year - old obese female was initially treated for pseudotumor cerebri with placement of a lumbar peritoneal shunt in 2003 .\nafter 5 failed revisions for nonfunction , a ventriculoperitoneal shunt was placed in september 2007 .\nthe patient subsequently presented 11 days postoperatively with headaches , dizziness , and formation of a seroma in her right upper quadrant .\nct scan revealed the vp catheter tubing coiled in the subcutaneous tissue of the right upper quadrant .\nfour 5-mm titanium clips were placed on the catheter in an attempt to prevent repeated migration of the tubing .\none month later , the patient presented with recurrence of headaches , nausea , and right upper quadrant abdominal pain .\nct scan was again obtained , revealing that the shunt tubing had migrated back into the subcutaneous tissue ( figure 1 ) .\na laparoscopic approach was again utilitzed for retrieval and attempted improved fixation of the vp shunt .\nadhesions were taken down at the original entry site of the shunt , revealing a 2-cm fascial defect in the abdominal wall with the shunt tubing coiled within it ( figure 2 ) .\nthe tubing was brought down through the defect out of the subcutaneous space and into the peritoneal cavity ( figure 3 ) .\none port was upsized to 10 mm , and the tubing was externalized through the port and secured to a 3-cm x 10-cm piece of ptfe mesh with 30 prolene sutures ( figure 4 ) .\ncsf flow was confirmed , and the tubing attached to the mesh was reintroduced into the peritoneal cavity .\nthe mesh was secured to the abdominal wall by using spiral tacks and 0 gore - tex sutures ( figure 5 ) .\nthe separate 2-cm fascial defect was repaired with a 10-cm x 10-cm piece of ptfe mesh placed as an onlay with the vp shunt exiting from its inferior border .\nit was secured with spiral tacks and 0 gore - tex sutures for transabdominal fixation ( figure 6 ) .\nthe patient was seen in follow - up 7 months postprocedure and reported no recurrence of her symptoms .\ntraditionally , laparotomy was necessary for both peritoneal shunt placement as well as subsequent shunt revisions .\nthe advent of laparoscopy has afforded a minimally invasive approach that has resulted in decreased patient morbidity related to shunt placement .\nretrieval and repositioning of a displaced vp shunt in the peritoneal cavity using laparoscopic techniques has been previously described . in the present case ,\nour subsequent laparoscopic approach utilized ptfe mesh , well described in the use of laparoscopic ventral hernia repair , to fixate the tubing to the abdominal wall to prevent further tubing migration .\nthis approach also allowed us to simultaneously repair the fascial defect associated with the shunt entry site into the peritoneal cavity , allowing us to reap the benefits of decreased recurrence and decreased patient morbidity associated with this technique .\nthe technique described was well tolerated without complication and resulted in improvement of clinical symptoms .", "answer": "a 31-year - old female with a history of pseudotumor cerebri presented with headache and abdominal discomfort after placement of a ventriculoperitoneal ( vp ) shunt . \n the vp shunt was placed after prior failure and revision of a lumbar peritoneal shunt . \n computed tomography demonstrated shunt migration into the subcutaneous tissue . \n laparoscopy was used to reposition the vp shunt , directing the shunt toward the pelvis . \n the patient presented for further evaluation one month later , at which point the shunt was shown to have migrated into the subcutaneous tissue once again . \n laparoscopy was again used to reposition the shunt and affix it to the abdominal wall by using polytetrafluoroethylene ( ptfe ) mesh .", "id": 941} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nA computational study of the Hofmann elimination pathway for the Morita-Baylis-Hillman reaction under DABCO catalysis. Participation of a bridge-head ylide\n\nPaper sections:\n\nWe have carried out a computational study of the Me3N-catalyzed MBH reaction and recently reported an alternate overall lower energy pathway. 4 This pathway involved proton-transfer in the aldol product through a seven-centred cyclic transition state structure, followed by Hofmann elimination to form the observed product and also regenerate the catalyst as shown in Scheme 2. TS1, TS2, TS3 and TS4 represent, respectively, the transition states for conjugate addition of Me3N to cyclopentenone to form an enolate 3, aldol reaction of the enolate with acetaldehyde to form the oxyanion 5, proton-transfer from one of the methyl groups on N to the oxyanion to form 6b and Hofmann elimination to generate the MBH product 7. The energy required to achieve TS2 was merely 2.6 kcal/mol and, likewise, the activation energy for the Hofmann elimination, 9.3 kcal/mol, was significantly lower than that for the proton-transfer through four-centred cyclic TS structure, 24.2 kcal/mol, which is accompanied immediately with E1cB elimination.
\n\nScheme 2. The proposed reaction pathway for the MBH reaction of cyclopentenone and acetaldehyde catalyzed by trimethylamine\nHaving shared the finding with a good colleague, 5 concern was raised as to whether the same was permissible with DABCO (1,4-diazabicyclo[2.2.2]octane) also because it would have to generate a bridge-head zwitterion. A truly genuine concern as it was, we felt wanted to investigate a parallel of the Me3N-catalyzed reaction by using DABCO as the catalyst.
Computational methods. All the structures, geometry optimizations and TS structure searches were carried out using the global hybrid meta-GGA M06-2X density functional and 6-311++G(d,p) basis set at 298.15 K. 6 The optimized structures were verified as minima or first order saddle points on their potential energy surfaces by harmonic vibrational frequency analysis. Calculations were carried out using the Gaussian 16 suite of programs. 7
Results and Discussion. We approached the problem by first studying the simpler DABCO, N-methyl-DABCO and the ylide formed from deprotonation at the position adjacent to the bridge-head. The computed structures of the two species are given in Figure 1. The difference in the structures is in the shape of the ring which is a clear boat in DABCO and N-methyl-DABCO, and twist-boat in the ylide.
The survival of the bride-head ylide as a stable structure instilled confidence in us to proceed and estimate the entire reaction profile of the MBH reaction of cyclopentenone with acetaldehyde catalyzed by DABCO. The reaction profile of the DABCO-catalyzed reaction is given in Figure 2. This profile is much similar to the Me3N-catalyzed reaction in every respect. In particular, the activation free energy for (a) the proton-transfer through seven-centred cyclic TS structure is 2.4 kcal/mol against the 2.6 kcal/mol under Me3N-catalysis, (b) the Hofmann elimination is 11.2 kcal/mol against the 9.3 kcal/mol under Me3N-catalysis, (c) the aldol reaction is 39.8 kcal/mol against the 41.9 kcal/mol under Me3N-catalysis, (d) the conjugate addition is 27.7 kcal/mol against the 29.6 kcal/mol under Me3N-catalysis, and (e) the proton-transfer through four-centred cyclic TS structure, as in the conventional mechanism, is 25.0 kcal/mol against the 24.2 kcal/mol under Me3N-catalysis. The aldol reaction continues to be the rate-limiting reaction in the entire sequence. However, a remarkable feature to note in here is the lower activation free energy of the DABCO-catalyzed aldol reaction than the Me3N-catalyzed reaction by 2.1 kcal/mol. The DABCO-catalysis is, therefore, expected to result in a faster reaction than Me3N-catalysis.
We have calculated the deuterium isotope effects, KH/KD, for the conventional route involving protontransfer through a four-centred cyclic transition state structure and the present Hofmann elimination route and found it to be 1.36 in each instance. Several MBH reactions under solvent-less conditions have been reported in the literature and often found to be faster and superior yielding than the reactions in solvents. 8
\n\nConclusion.\nThe DABCO-catalysis of MBH reaction parallels the catalysis by Me3N and the perceived difficulty of generating a bridge-head zwitterion is just not there as anticipated from the preliminary investigations on the structural aspects of N-methyl-DABCO and the consequent bridge-head ylide.
The DABCO-catalyzed Hofmann elimination pathway for the MBH reaction is also lower in energy than the conventional pathway requiring proton-transfer through a four-centred cyclic TS structure to form a species ready for E1cB elimination. Also, for lowering the activation free energy of the rate-limiting aldol reaction by 2.1 kcal/mol, DABCO is expected to result in a faster reaction than Me3N.
The study of the influence of solvents 9 on the overall reaction profile and the associated kinetic isotope effect kH/kD is under investigation.
\n\nSupporting Information\nSupporting Information (SI) available: Cartesian coordinates of the optimized substrates, transition state structures, Gibbs' free energies of the ground and transition state structure studied at the level M06-2X/6-311++G(d,p).
\n\nORCID\nVeejendra K. Yadav: 0000-0001-8294-0677
", "answer": "In comparison to the popular pathway involving proton-transfer via a four-centred cyclic transition state structure, the recently proposed overall lower energy pathway involving protontransfer via a seven-centred cyclic transition state structure followed by Hofmann elimination for the Me3N-catalyzed Morita-Baylis-Hillman reaction is applicable to the DABCO-catalyzed reaction equally well. This finding clearly establishes that the zwitterion at the bridge-head in DABCO is well tolerated. Also, the activation free energy of the rate-limiting aldol reaction under DABCO-catalysis is lower than that under Me3N-catalysis, suggesting that DABCO is likely a better catalyst to achieve faster conversion.Introduction. The Morita-Baylis-Hillman (MBH) reaction, Scheme 1, is a broad range, synthetically useful chemical transformation allowing the construction of a myriad of densely functionalized \uf061methylene-\uf062-hydroxy derivatives. 1,2 The reaction involves coupling of an electrophile, such as an aldehyde, with an activated alkene (normally with an electron-withdrawing group) in the presence of a Lewis base catalyst such as Me3N, DABCO and DBU. Based on its atom economy and feasibility, the MBH reaction is regarded as one of the most efficient transformations in organic chemistry. 3 According to the generally accepted mechanism, the aldol product 5 undergoes a proton-transfer reaction by the way of a four-centred cyclic transition state (TS) structure, as shown, to form the 1,3-zwitterion 6a, which falls through E1cB elimination, as shown, to the MBH product 7 and also regenerate the Lewis base to allow it re-enter the reaction cycle. The reaction, therefore, is catalytic in the Lewis base.Scheme 1. The generally accepted pathway for the Me3N-catalyzed MBH reaction of cyclopentenone with acetaldehyde", "id": 942} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthis study reports a rare patient of a rapid spontaneously resolving acute subdural hematoma . in addition\n, an analysis of potential clues for the phenomenon is presented with a review of the literature .\na 1-year - and-2-month - old boy fell from a height of approximately 2 m. the patient was in a superficial coma with a glasgow coma scale of 8 when he was transferred to the authors hospital .\ncomputed tomography revealed the presence of an acute subdural hematoma with a midline shift beyond 1 cm .\nrepeat imaging after 15 hours showed the evident resolution of the hematoma and midline reversion .\nprogressive magnetic resonance imaging demonstrated the complete resolution of the hematoma , without redistribution to a remote site .\neven though this phenomenon has a low incidence , the probability of a rapid spontaneously resolving acute subdural hematoma should be considered when patients present with the following characteristics : children or elderly individuals suffering from mild to moderate head trauma ; stable or rapidly recovered consciousness ; and simple acute subdural hematoma with a moderate thickness and a particularly low - density band in computed tomography scans .\na 1-year - and-2-month - old boy fell from a height of approximately 2 m and lost consciousness after he experienced head trauma .\nthe patient was sent to a local hospital immediately . during the interval emergent computed tomography ( ct ) , the patient vomited several times .\n1a ) revealed a right frontotemporal asdh that was approximately 9 mm in size with a subarachnoid hemorrhage in the longitudinal fissure and midline shift beyond 10 mm .\nhe was in a superficial coma with the same gcs score that was documented in previous medical records .\nboth of the patient 's pupils were equal in size 2 mm but exhibited a blunted response to light .\n1b ) showed a decrease in hematoma density and diffuse cerebral edema with obviously squeezed ventricles ; the midline was still deviated compared with the first ct scan .\ngiven his consciousness and imaging findings , intracranial pressure monitoring was preferred . even though the laboratory features were not surgical contraindications , the boy 's guardians refused the placement of an intracranial pressure probe or a craniotomy .\ngeneral monitoring aimed to maintain sao2 at > 95% , mean systolic blood pressure at > 90 mm hg , temperature at < 37c , and paco2 at 35 to 40 mm hg . owing to the lack of an accurate intracranial pressure assessment\n, mannitol was administered empirically at 0.5 g / kg every 6 hours . the third ct scan ( fig .\n1c ) revealed evident resolution of the hematoma and midline shift improvement , with only a subarachnoid hemorrhage present in the posterior longitudinal fissure 24 hours after the trauma . after he had received 2 days of conservative management , the boy regained consciousness .\nc ) showed that the asdh was almost completely resolved on the fourth day after admission , without redistribution to the upper cervical spinal cord .\n( a ) initial ct scan revealed right frontotemporal acute subdural hematoma ( arrow to show ) , with sah in anterior longitudinal fissure and midline shift exceeding 10 mm .\n( b ) a second ct scan showed the decrease of hematoma ( arrow to show ) with obvious diffusion cerebral edema .\n( c ) a third ct scan was taken after 24 hours of the injury revealed an evident resolution of hematoma ( arrow to show ) and midline revert with only sah left in posterior longitudinal fissure .\nct , computed tomography ; sah , subarachnoid hemorrhage . magnetic resonance imaging on the fourth day of conservative management .\ntransverse ( a ) , sagittal ( b ) , and coronal ( c ) planes were performed which revealed acute subdural hematoma complete resolution without redistribution to upper cervical spinal cord .\nthe following 2 possible explanations were proposed : the asdh was diluted and washed out by cerebrospinal fluid ( csf ) after the tearing of the arachnoid membrane and the hematoma was redistributed to the subdural space .\nwong et al measured the hounsfield units of the subarachnoid space , which was close to normal , and confirmed the redistribution of a hematoma to the subdural space then to the subarachnoid space .\nthe theory was based on the flow of liquefied blood , which was thought to be driven by the change in intraparenchymal pressure . in those patients without available definitive evidence of blood redistribution , csf flushing seems more likely .\nbased on table 1 , rapid resolution occurred more frequently in children , less frequently in elders , and least often in middle - age individuals . in children and elders ,\nasdh is often caused by mild or moderate injuries , such as falling or slipping .\nin elderly individuals , brain atrophy and a wide cavum of the subarachnoid space can cause an arachnoid membrane slit under external force . for middle - age individuals , well - developed brain tissue and narrow compensatory space results in an arachnoid membrane that is comparatively difficult to tear with a mild injury .\nwen et al proposed that gcs was higher than 8 in patients who exhibited this phenomenon .\nhowever , in table 1 , 7 of 18 patients exhibited a gcs score of less than 8 , and the minimum was 5 . in the process of the clinical evaluation ,\nthe dynamic change in consciousness is a more heavily weighted factor to consider than the initial gcs score . according to a review of all patients ( table 1 ) , most of those patients regained consciousness quickly .\nalthough some of those patients did not regain consciousness quickly , their conditions were stable . in our case ,\nthe patient 's consciousness improvement was even slower than the time of resolution according to the ct scan .\nthus , by comparing the initial gcs score after head trauma , we inferred that a rapid recovery or relative stabilization of consciousness is more persuasive in these patients .\nthe evaluation of images from ct scans that were performed during different phases of our patient clearly demonstrated the rapid transition of hematoma density from a high density to a mixed density .\nsome authors agreed that the potential sign in early ct of a rapid resolution was the presence of a low - density band . in our patient 's second ct scan ( fig .\n1b ) , it was observed that remarkable cerebral edema could squeeze , in some way , the diluted hematoma .\nkuroiwa et al suggested that diffuse cerebral edema was necessary for the spontaneous resolution of a hematoma .\nwe speculate that cerebral edema leads to resolution via both mechanisms , but it may not be the prerequisite for hematoma rapid resolution . indeed ,\nin most patients , the diffuse edema was not even observed ( table 1 ) .\nwe propose that the slice or middle thickness hematoma ( < 1.5 cm ) would be suitable in the consideration of rapid resolution .\nlee et al reported a patient with a hematoma thickness that was larger than 2.5 cm , yet it finally converted to a chronic subdural hematoma .\nthe presence of simple asdh without contusion appears to be associated with rapid resolution . we suspect that this effect is due to the mass effect of the contusion , which impeded the flow of csf in the limited space .\nthis patient has been reported because of clear evidence of csf dilution and a flush effect that led to resolution of the hematoma , and the finding that a distinctly swollen brain probably accelerated the process .\nthere is no need for the deliberate evaluation of the phenomenon as a coincidence during treatment .\nwe suggest that asdh rapid resolution should be considered when patients present with the following characteristics : children or elders suffering from mild to moderate head trauma ; stable or rapidly recovered consciousness ; and simple asdh with moderate thickness and a particularly low - density band in ct scan images .", "answer": "introduction : this study reports a rare patient of a rapid spontaneously resolving acute subdural hematoma . in addition , an analysis of potential clues for the phenomenon is presented with a review of the literature.patient presentation : a 1-year - and-2-month - old boy fell from a height of approximately 2 m. the patient was in a superficial coma with a glasgow coma scale of 8 when he was transferred to the authors hospital . \n computed tomography revealed the presence of an acute subdural hematoma with a midline shift beyond 1 cm . \n his guardians refused invasive interventions and chose conservative treatment . \n repeat imaging after 15 hours showed the evident resolution of the hematoma and midline reversion . \n progressive magnetic resonance imaging demonstrated the complete resolution of the hematoma , without redistribution to a remote site.conclusions:even though this phenomenon has a low incidence , the probability of a rapid spontaneously resolving acute subdural hematoma should be considered when patients present with the following characteristics : children or elderly individuals suffering from mild to moderate head trauma ; stable or rapidly recovered consciousness ; and simple acute subdural hematoma with a moderate thickness and a particularly low - density band in computed tomography scans .", "id": 943} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmost osteoporotic compression fractures heal with mild residual deformities , and clinical complications are usually rare5 ) .\nwhen conservative treatment offers no symptomatic improvement , percutaneous vertebroplasty or balloon kyphoplasty have been safely used and have provided rapid pain relief with mechanical stabilization10 ) . sometimes , however , patients complain about both back pain and newly developed leg pain following vertebral compression fractures\n. the main symptom can be radicular leg pain , rather than axial pain , which mimics foraminal stenosis or disc herniation .\nthis radiculopathy is thought to be caused by the encroachment of the intervertebral foramen2 ) . in those cases ,\nit is difficult to perform bone cement augmentation because it is known that percutaneous vertebroplasty is a relative contraindication to the conditions causing radicular symptoms in patients who present with canal encroachment1 ) .\nthis study aimed to investigate the risk for newly developed radiculopathic leg pain following lumbar osteoporotic compression fracture by analyzing the fracture pattern .\nwe also studied whether bone cement augmentation would lead to a good or poor clinical outcome .\nbetween may 2008 and april 2010 , 238 patients underwent single - level vertebroplasty or balloon kyphoplasty for osteoporotic compression fractures in our institute .\nthe inclusion criteria were as follows : 1 ) fracture location under l2 level that can lead to radiculopathic leg pain following vertebral compression fracture ; 2 ) osteoporotic spine ( t - score by bone mineral densitometry lower than -3.0 ) ; 3 ) follow - up period longer than 6 months ; and 4 ) no radiculopathic leg pain before the osteoporotic compression fracture .\npatients with obvious burst fractures at the time of injury , with previous history of spine surgery or radiculopathic symptom before compression fracture , were excluded in this study . of these 238 patients , 59 who had osteoporotic compression fractures and underwent percutaneous vertebroplasty or balloon kyphoplasty under the l2 level\nwere enrolled in this study . to study whether the fracture pattern influences the newly developed radiculopathy and back pain ,\nthe 59 patients were divided into two groups , namely group a ( n=44 ) , back pain - only , and group b ( n=15 ) , back pain with newly developed unilateral leg pain .\nfractures were evaluated using early magnetic resonance imaging ( mri ) based on kanchiku 's method and we classified into three types according to the main position of the fracture line on the basis of t1 , t2-weighted fat and suppression images ( superior , middle , and inferior ) ( fig .\nthe preoperative group differences data were evaluated by the unpaired student t - test using the spss program ( spss inc . , chicago , il , usa ) , and intragroup changes associated with the procedure were evaluated using the student t - test for paired data with a p<0.01 considered the significance level .\nthe anatomical distribution of the 59 patients was as follows : l2 ( n=19 ) , l3 ( n=18 ) , l4 ( n=14 ) , and l5 ( n=8 ) . among them\nthere were no significant differences between group a and group b with respect to age and gender .\nthe overall incidence of radiculopathic leg pain under the l2 level was 25% ( n=15 ) .\nthere was no newly developed radiculopathy at the l2 level , and the frequency of radiculopathic leg pain increased with descending levels ( table 1 ) .\nalthough vertebral collapse was not severe in lumbar radiographs and mri , 10 of 15 patients in the group b showed compression fracture and suspicious impingement of the corresponding nerve root at the intervertebral foramen . in the analysis of fracture pattern under the l2 level , which showed radiculopathy , only the back pain group ( group a ) demonstrated symptoms relating to the superior fracture type .\nhowever , the fracture pattern in the group with back and radiculopathic pains ( group b ) was mostly related to the inferior fracture type ( table 2 ) .\nsuch a difference was statistically significant ( p<0.01 ) and can be attributed to the different pathophysiological mechanism in the two groups ( fig .\nthe mean back pain score of both groups showed significant improvement at the last follow - up .\ninterestingly , the mean pain score of leg pain in group b also showed significant improvement after bone cement augmentation without decompressive open surgery .\nthe visual analogue scale decreased from a preoperative score of 6.5 to 3.0 at 7 postoperative days and it was maintained at final follow - up with respect to radiculopathy ( fig .\n3 ) . three patients ( 2 in l4 and 1 in l5 ) in group b had recurrent radicular pain during the follow - up period , but their pain was tolerable , as controlled by analgesics ( fig . 4 , 5 ) .\nin the analysis of fracture pattern under the l2 level , which showed radiculopathy , only the back pain group ( group a ) demonstrated symptoms relating to the superior fracture type .\nhowever , the fracture pattern in the group with back and radiculopathic pains ( group b ) was mostly related to the inferior fracture type ( table 2 ) .\nsuch a difference was statistically significant ( p<0.01 ) and can be attributed to the different pathophysiological mechanism in the two groups ( fig .\nthe mean back pain score of both groups showed significant improvement at the last follow - up .\ninterestingly , the mean pain score of leg pain in group b also showed significant improvement after bone cement augmentation without decompressive open surgery .\nthe visual analogue scale decreased from a preoperative score of 6.5 to 3.0 at 7 postoperative days and it was maintained at final follow - up with respect to radiculopathy ( fig .\n3 ) . three patients ( 2 in l4 and 1 in l5 ) in group b had recurrent radicular pain during the follow - up period , but their pain was tolerable , as controlled by analgesics ( fig . 4 , 5 ) .\ncompression fractures caused by osteoporosis are common in the elderly and are often encountered by spine surgeons .\nit is well known that bone cement augmentation procedures such as percutaneous vertebroplasty or balloon kyphoplasty improve back pain from osteoporotic compression fractures4,8 ) . however , in some instances , lumbar osteoporotic compression fractures without evident canal compromise cause radiculopathic radiating pain and spinal canal stenosis leading to claudication7 ) .\nconservative treatment using a lumbar brace for compression fracture forces the posture in lumbar extension , worsening central or foraminal stenosis2 ) .\nsurgical treatment of lumbar stenosis with open decompression with instrumented stabilization has the potential for significant complications because of comorbidities related to advancing age , especially severe osteoporosis and high risk for instrumentation failure9 ) .\nthis study was performed to clarify and analyze whether an early fracture pattern based on mri classification influences the newly developed radiculopathy in osteoporotic compression fractures and clinical outcome after bone cement augmentation procedure . in this study , the incidences of acute and newly developed leg pain after\nthe possible cause of radiculopathic leg pain after osteoporotic compression fracture may be considered to be the following mechanism : when the osteoporotic vertebral fracture occurs , if the bony fragments from the collapsed body invade the foraminal space , the root can be compressed directly , leading to radiculopathy .\nthe decreased foraminal height by vertebral body collapse will be worse . by categorizing fractures on the basis of fracture line\nthe second plausible mechanism may be considered to be a referred pain , which is distributed far from the site of injury .\ndoo et al.3 ) reported that the posterior branches can be irritated by the narrowing of the intervertebral foramen resulting from the decreased height of the vertebral bodies , their pain may have been distributed in these areas as a radicular or somatic referred pain .\nwe performed bone cement augmentation alone because it is a simple and less invasive procedure , and it was efficacious in providing satisfactory pain relief , not requiring open decompressive surgery even in radiculopathy .\nthe pain relief mechanisms by vertebral augmentation procedures may be deduced as the following mechanism .\nfirst , segmental stability provided by the cement augmentation is increased , and second , retropulsion and foraminal narrowing are decreased . as spondylotic changes progress in the lumbar spine during aging , the foraminal space decreases with facet hypertrophy , reduced disc height , and foraminal or extraforaminal disc herniations .\nactually , the radicular pain in most patients in group b was aggravated in the erect position .\nbecause the posterior wall of the vertebral body inferior to the pedicle constitutes a large portion of intervertebral foramen , the size of the intervertebral foramen will diminish when the compression fracture involves that part of the vertebra .\nif the root impingement occurs by a combination of spondylotic foraminal stenosis and vertebral fracture , the degree of root compression will increase by weight loading because of the decreased stiffness of the vertebral body . if this is the main mechanism of the patients ' symptoms , bone cement augmentation may play a major role in relieving the radicular pain secondary to some degree of fracture reduction and mechanical stabilization .\nwe could achieve favorable clinical outcome by bone cement augmentation procedure alone . despite our successful results ,\nthe authors ' proposed pathomechanism is presumptive and is supported mainly by the patient 's immediate and symptomatic improvement during follow - up . for a more scientific approach to this subject , experimental data include accurate measurement of the size of the intervertebral foramen according to the weight loading in a fractured vertebra .\nexperimental study with the finite element model can be a good method that can confirm our results . in the near future ,\nrandomized clinical trials for comparative studies in a larger population for a longer period are necessary .\nby categorizing fractures on the basis of fracture line , we found that inferior - type fractures were more related to the development of radiculopathic leg pain .\nbone cement augmentation alone can be a safe and efficient option in patients with painful osteoporotic compression fracture and radiculopathy .", "answer": "objectivethe purpose of this study was to analyze the relationship between fracture pattern and the development of acute radiculopathy after osteoporotic lumbar compression fracture.methodsthis study included 59 patients who underwent bone cement augmentation for osteoporotic compression fracture below the l2 level , which can lead to radiculopathic radiating pain . \n the patients were divided into two groups according to the presence of radiculopathy ( group a : back pain only ; group b : back pain with newly developed radiating pain ) . \n we categorized compression fractures into three types by the position of the fracture line . \n the incidence of newly developed radiculopathy was examined retrospectively for each compression fracture type.resultsthe overall incidence of newly developed leg pain ( group b ) was 25% , and the frequency increased with descending spinal levels ( l2 : 0% , l3 : 22% , l4 : 43% , and l5 : 63% ) . \n the back pain - only group ( group a ) had mostly superior - type fractures . on the other hand , the back pain with radiculopathy group ( group b ) had mostly inferior - type fractures . \n most patients in group b showed significant relief of leg pain as well as back pain after bone cement augmentation.conclusionthe incidence of a newly developed , radiating pain after osteoporotic compression fractures increased gradually from the l3 to l5 levels . \n most of these fractures were of the inferior type , and the bone cement augmentation procedures seemed to be sufficient for relief of both back and radiating pain .", "id": 944} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfear of hypoglycaemia and gain in body weight act as barriers for initiation of insulin therapy .\nmodern insulin analogues are a convenient new approach or tool to glycaemic control , associated with low number of hypos and favourable weight change .\na1chieve , a multinational , 24-week , non - interventional study , assessed the safety and effectiveness of insulin analogues in people with t2 dm ( n = 66,726 ) in routine clinical care .\nplease refer to editorial titled : the a1chieve study : mapping the ibn battuta trail .\nthe patient characteristics for the entire cohort divided as insulin - nave and insulin users is shown in the table 1 .\nthe majority of patients ( 71.28% ) started on or switched to biphasic insulin aspart .\nother groups were insulin detemir ( n = 28 ) , insulin aspart ( n = 24 ) , basal insulin plus insulin aspart ( n = 13 ) and other insulin combinations ( n = 3 ) . overall demographic data after 24 weeks of treatment , overall hypoglycaemic events reduced from 2.1 events / patient - year to 0.0 events / patient - year in insulin nave group and from 6.8 events / patient - year to 0.0 events / patient - year in insulin users group .\nthe hypoglycaemia incidence in insulin naive group at 24 weeks was lower than that observed in insulin users at baseline .\nmajor hypoglycaemic events decreased from 0.5 events / patient - year to 0.0 events / patient - year in insulin nave group while no change from baseline ( 1.3 events / patients - year ) was observed for insulin user group .\nmean hba1c and fpg values improved from baseline to study end in the insulin nave group [ table 4 ] .\noverall efficacy data of the total cohort , 340 patients started on biphasic insulin aspart ogld , of which 153 ( 45% ) were insulin nave and 187 ( 55% ) were insulin users .\nafter 24 weeks of starting or switching to biphasic insulin aspart , hypoglycaemic events reduced from 2.3 events / patient - year to 0.0 events / patient - year in insulin nave group and from 6.3 events / patient - year to 0.0 events / patient - year in insulin users .\nquality of life improved at the end of the study [ table 5 and 6 ] .\nbiphasic insulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to biphasic insulin aspart for insulin nave group [ table 7 ] .\nbiphasic insulin aspartoral glucose - lowering drug efficacy data of the total cohort , 7 patients started on basal + insulin aspart ogld , of which 2 ( 28.6% ) were insulin nave and 5 ( 71.4% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 10.4 events / patient - year to 0.0 events / patient - year in insulin users whereas hypoglycaemia remained nil in insulin naive group , similar to baseline .\nquality of life improved after 24 weeks of treatment [ table 8 and 9 ] .\nbasal+insulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to basal + insulin aspart oglds for insulin nave group . of the total cohort ,\n90 patients started on insulin detemir ogld , of which 57 ( 63.3% ) were insulin nave and 33 ( 36.7% ) were insulin users .\nafter 24 weeks of starting or switching to insulin detemir , hypoglycaemic events reduced from 2.5 events / patient - year to 0.0 events / patient - year in insulin nave and from 6.3 events / patient - year to 0.0 events / patient - year in insulin user groups [ table 10 and 11 ] .\ninsulin detemiroral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to insulin detemir oglds for insulin - nave group [ table 12 ] .\ninsulin detemiroral glucose - lowering drug efficacy data of the total cohort , 37 patients started on insulin aspart ogld , of which 26 ( 70.3% ) were insulin nave and 11 ( 29.7% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 14.2 events / patient - year to 0.0 events / patient - year in insulin users whereas , hypoglycaemic events remained nil in insulin users , similar to baseline .\nquality of life improved at the end of the study [ table 13 and 14 ] . insulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to insulin aspart oglds for insulin nave group [ table 15 ] .\nof the total cohort , 340 patients started on biphasic insulin aspart ogld , of which 153 ( 45% ) were insulin nave and 187 ( 55% ) were insulin users .\nafter 24 weeks of starting or switching to biphasic insulin aspart , hypoglycaemic events reduced from 2.3 events / patient - year to 0.0 events / patient - year in insulin nave group and from 6.3 events / patient - year to 0.0 events / patient - year in insulin users .\nquality of life improved at the end of the study [ table 5 and 6 ] .\nbiphasic insulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to biphasic insulin aspart for insulin nave group [ table 7 ] .\nof the total cohort , 7 patients started on basal + insulin aspart ogld , of which 2 ( 28.6% ) were insulin nave and 5 ( 71.4% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 10.4 events / patient - year to 0.0 events / patient - year in insulin users whereas hypoglycaemia remained nil in insulin naive group , similar to baseline .\nquality of life improved after 24 weeks of treatment [ table 8 and 9 ] .\nbasal+insulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to basal + insulin aspart oglds for insulin nave group .\nof the total cohort , 90 patients started on insulin detemir ogld , of which 57 ( 63.3% ) were insulin nave and 33 ( 36.7% ) were insulin users .\nafter 24 weeks of starting or switching to insulin detemir , hypoglycaemic events reduced from 2.5 events / patient - year to 0.0 events / patient - year in insulin nave and from 6.3 events / patient - year to 0.0 events / patient - year in insulin user groups [ table 10 and 11 ] .\ninsulin detemiroral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to insulin detemir oglds for insulin - nave group [ table 12 ] .\nof the total cohort , 37 patients started on insulin aspart ogld , of which 26 ( 70.3% ) were insulin nave and 11 ( 29.7% ) were insulin users .\nafter 24 weeks of treatment , hypoglycaemic events reduced from 14.2 events / patient - year to 0.0 events / patient - year in insulin users whereas , hypoglycaemic events remained nil in insulin users , similar to baseline .\nquality of life improved at the end of the study [ table 13 and 14 ] .\ninsulin aspartoral glucose - lowering drug safety data mean hba1c and fpg values improved from baseline to study end in those who started on or were switched to insulin aspart oglds for insulin nave group [ table 15 ] .\nour study reports improved glycaemic control ( hba1c , fpg ) following 24 weeks of treatment with any of the insulin analogues ( biphasic insulin aspart ; basal + insulin aspart ; insulin detemir ; insulin aspart ) with or without ogld .\nmajor hypoglycaemic events decreased from 0.5 events / patient - year to 0.0 events / patient - year in insulin nave group while no change from baseline ( 1.3 events / patients - year ) was observed for insulin user group .\noverall , body weight reduced in insulin nave group whereas no change in body weight was observed for insulin users .\nthough the findings are limited by number of patients , still the trend indicates that insulin analogues can be considered effective and possess a safe profile for treating type 2 diabetes in rajasthan , india .", "answer": "background : the a1chieve , a multicentric ( 28 countries ) , 24-week , non - interventional study evaluated the safety and effectiveness of insulin detemir , biphasic insulin aspart and insulin aspart in people with t2 dm ( n = 66,726 ) in routine clinical care across four continents.materials and methods : data was collected at baseline , at 12 weeks and at 24 weeks . this short communication presents the results for patients enrolled from rajasthan , india.results:a total of 477 patients were enrolled in the study . \n four different insulin analogue regimens were used in the study . \n patients had started on or were switched to biphasic insulin aspart ( n = 340 ) , insulin detemir ( n = 90 ) , insulin aspart ( n = 37 ) , basal insulin plus insulin aspart ( n = 7 ) and other insulin combinations ( n = 2 ) . at baseline \n glycaemic control was poor for both insulin nave ( mean hba1c : 8.3% ) and insulin user ( mean hba1c : 8.4% ) groups . \n after 24 weeks of treatment , both the groups showed improvement in hba1c ( insulin nave : 0.9% , insulin users : 1.2% ) . \n major hypoglycaemic events decreased from 0.5 events / patient - year to 0.0 events / patient - year in insulin nave group while no change from baseline ( 1.3 events / patients - year ) was observed for insulin users . \n sadrs were not reported in any of the study patients.conclusion:starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia .", "id": 945} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrituximab is a relatively novel medication for immunomodulation in current clinical practice . with its use becoming fairly widespread and newer indications being approved at a fast rate it is also imperative to watch for any adverse reactions , which may need monitoring parameters during therapy\na 54-year - old man was diagnosed with limited form of wegener 's granulomatosis 1 year before the current hospitalization .\nhe had failed therapy with corticosteroids and was recommended rituximab for resistant disease state . besides lung and upper airway involvement , he had no other organ involvement from wegener 's disease .\nfive days after receiving the infusion he developed postural dizziness and had near syncopal episodes , which led to hospital admission .\nhe denied chest pain , shortness of breath , fever , palpitations , and any rash .\nvital signs on admission revealed hypotension with a blood pressure of 80/40 mmhg , pulse 75 beats / min , respiratory rate 20/min , and temperature 98f .\nelectrocardiogram ( ecg ) showed a new onset left bundle branch block ( lbbb ) [ figure 1c ] as compared to his prior ecg performed a month back before the current admission [ figure 1a ] . in view of new lbbb\n, an urgent transthoracic echocardiogram was performed revealing normal left ventricular systolic function and absence of wall motion abnormalities .\npatient was admitted to intensive care unit and was treated with intravenous fluids and inotropic agents for hypotension .\ncontrast - enhanced cardiac magnetic resonance imaging was conducted to rule out focal myocarditis as a cause of the new onset lbbb ; and failed to show any abnormality . on day 2 of admission ,\ntelemetry showed intermittent lbbb [ figure 1b ] and eventually the lbbb was replaced by a narrow qrs complex [ figure 1d ] with only supportive treatment .\npatient remained hemodynamically stable off inotropic agents and was discharged home and is doing well on follow up .\ntelemetric strip new onset left bundle branch block ( lbbb ) intermittent sinus beats with lbbb and finally resolution of lbbb\nrituximab , the first monoclonal antibody approved by the united states food and drug administration ( fda ) for the treatment of malignant disease , is being used to treat a wide variety of conditions in modern practice , including non - hodgkin 's lymphoma , wegener 's granulomatosis , rheumatoid arthritis , thrombotic thrombocytopenic purpura , among many others .\ncurrently , four adverse effects that warrant a \" black box \" warning in the package insert are known : infusion reactions , tumor lysis syndrome , mucocutaneous reactions , and progressive multifocal leukoencephalopathy .\nit is also known to promote severe orthostatic hypotension often associated with allergic symptoms , urticaria , bronchospasm , and angioedema .\nmost adverse events occur during or after the first infusion of rituximab , and the number and severity of adverse events decreases with subsequent infusions . as with any novel therapy , new adverse reactions are being noted with increasing time and usage . in a multicenter phase\nii study conducted to assess the toxicity and response rates to rituximab in b - cell malignancies that express cd20 , 10 out of 131 patients developed an arrhythmia with treatment . these included bradycardia ( n = 3 ) , atrial fibrillation ( n = 2 ) , and nonspecified arrhythmia or tachyarrhythmia ( n = 5 ) .\none other patient had palpitations , and another was noted to have premature ventricular complexes . in most cases ,\nventricular tachycardia during the infusion of rituximab and prompt disappearance after discontinuation of infusion was first reported in 2005 .\ncomplete atrioventricular block induced by rituximab monotherapy in an 83-year - old has also been described in literature .\nanother recent report of polymorphic ventricular tachycardia causing syncope during initial infusion of rituximab raises concerns of arrhythmogenic side effects of this medication . despite these reports a study to determine\nthe maximum tolerated infusion rate of rituximab with special emphasis on monitoring the effect of rituximab on cardiac function concluded with confirmation of lack of cardiotoxic effect of a fast infusion rate .\nhowever , we could not come across any reported case of lbbb associated with rituximab infusion .\nincreased ventricular dysfunction after rituximab infusion has been seen which is attributed to growth of reticulin fiber in cardiac myocytes .\nreticulin deposition may have an effect on conduction system causing rhythm abnormalities and interventricular conduction delays as seen in our patient .\nit is also hypothesized that the drug affects conduction by inhibiting the calcium - ion channel properties of the cd20 antigen , which could lead to formation of early after depolarizations .\nstill the mechanism by which rituximab may cause arrhythmias is presently unclear and needs more research .\nalso , it would be prudent to keep patients on electrocardiac monitoring during drug infusions to monitor for possible conduction abnormalities , especially the initial infusions .", "answer": "rituximab ( a monoclonal antibody directed against cd 20 ) therapy can be acutely complicated by infusion reactions and cardiac arrhythmia on rare occasions . \n we report the first case of a new onset left bundle branch block ( lbbb ) after rituximab therapy for wegener 's vasculitis .", "id": 946} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthis special issue of fungal genetics and biology describes a comprehensive effort to develop methods and expertise to tackle one of the world s most serious fungal diseases of wheat .\nthe series of papers within this issue are designed to provide a resource for a new generation of plant pathologists who we hope will be inspired to investigate the biology of septoria blotch of wheat and develop new and durable disease control strategies .\nwheat is the world s most widely cultivated crop and is responsible for providing about a quarter of the calories to humankind .\nglobal wheat production was more than 700 million tons in 2013 , with the european union and china producing the largest harvests , and wheat being cultivated across most of the temperate regions of the planet ( gurr and fones , 2015 ; rudd et al . , 2015 ) .\nas well as being the most widely grown crop , wheat is also the most traded food on the international markets indeed more wheat is traded than all other crops combined . along with rice and maize ,\nthere are many threats to wheat productivity , including the availability of high quality land for cultivation , which is threatened by urbanisation , the sustainable use of fertilisers , which are used in enormous quantities , especially in europe , and the prevalence of diseases .\nwheat diseases , such as septoria blotch , provide an ever - present threat to wheat production and if they could be controlled effectively , would provide a much - needed boost to productivity that will be required to satisfy increasing global demand for food in the next two decades ( courbot et al . , 2015 ;\nwhat then are the essential pre - requisites to allow us rapidly to understand the biology of zymoseptoria tritici ? what requirements are necessary to allow a fungal pathogen to be regarded as a model system ( perez - nadales et al . , 2014 ) and for new insights into the underlying mechanisms of infection and virulence to be understood ?\nthe last 20 years have seen pathogens , such as the corn smut fungus ustilago maydis and the rice blast fungus magnaporthe oryzae , for example , emerge as model systems ( dean et al . , 2012 ) .\nin both cases , this required the development of many tools , which took many years .\nit is by considering these issues that this collection of reviews and primary publications has been put together .\narguably , the first pre - requisite to being able to investigate any disease is a comprehensive description of the life cycle of the organism and the spatial and temporal dynamics of the infection process . for z. tritici\nthis means a cell biological investigation of what happens from the moment a spore germinates on the leaf surface , to its location of a stoma and invasion of underlying leaf tissue .\nusing live cell imaging approaches , facilitated by the tools generated and described elsewhere in this special issue , the cell biology of infection is addressed , with an emphasis on the developmental biology of the fungus , its dimorphic growth habit , its ability to perceive and respond to the leaf surface , and its ability to undertake developmental transitions during its establishment of a wheat infection ( steinberg , 2015 ) . without a road - map of how an infection proceeds , it is difficult to identify points of disease intervention or to understand how any single gene product , or family of proteins ( from the pathogen or its host ) , might be important in disease .\nthe next essential pre - requisite for the model pathogen tool - kit is the ability to test the function of any gene . without an ability to construct mutants ,\nit is hard to carry out any reverse genetic approach to test the importance of any selected biological process .\ntherefore , a high frequency transformation system is essential , with a ready supply of selectable marker genes to allow multiple constructs to be expressed , and the ability to carry out targeted mutations ( kilaru and steinberg , in 2015 ; kilaru et al . , 2015a ; schuster et al . ,\nthe latter can be dramatically improved by development of a strain of z. tritici in which the non - homologous dna end - joining pathway is impaired ( sidhu et al .\ncoupled to this , it would be advantageous to have a means by which the function of a gene could be attenuated but without complete loss of function , such as virus - induced gene silencing , and the ability to regulate genes driven by a set of highly controllable promoters by which gene expression can be predictably controlled ( kilaru et al .\nthe latter will also provide the means to over - express , or mis - time the expression of a given gene to tests its function , or requirement ( cairns et al . , 2015 ) .\nnext , a means by which gene products can be localised using expression of fluorescently - labelled fusion proteins is essential , preferably with optimised fluorescent markers , calibrated and tested for the pathogen and in amenable vectors , with easy cloning strategies for ready construction ( kilaru et al .\n, 2015c ; mehrabi et al . , 2015 ; schuster et al . , 2015a ; sidhu et al .\nthis provides the means to carry out live cell imaging of a pathogen undergoing infection and directly observing the position , fate and turnover of a gene product , which is absolutely pivotal to understanding its function . but this will make no sense without some context , so having the ability to unequivocally identify organelles , such as nuclei , er , golgi bodies , peroxisomes , and mitochondria is essential ( schuster et al . , 2015b ; kilaru et al . , 2015b ; guo et al .\n, 2015a , b ) . also , to understand intracellular trafficking it is necessary to be able to identify and track the movement of endosomes , secretory vesicles and the associated components of the actin and microtubule cytoskeleton and their corresponding motor proteins , so that the transport of proteins and the regulation of such processes can be studied ( guo et al . , 2015a , b ; kilaru et al . , 2015c ; schuster et al .\nwhen considered together , these tools will therefore allow rapid elucidation of gene function in z. tritici , as rapidly as in any fungal pathogen studied today .\nso far , of course , we have only considered addressing the functions of individual genes as opposed to gene families and the function of the whole genome and the corresponding , context - dependent proteomes that are expressed during pathogenesis . to address these\nrequires first of all a detailed understanding of the genome ( goodwin et al . , 2011 ; testa et al . , 2015 ) and its inherent , strain - to - strain variation , and how this correlated with pathotype .\nunderstanding the role , for example , of accessory , or supernumerary chromosomes , as opposed to the core , invariant gene repertoire of the genome will be key ( mcdonald et al . , 2015 ) . an ability to analyse global patterns of gene expression , proteomic and metabolomics data sets during infection , will also be necessary so that the total expressed proteome can be defined and sub - sets associated with the effector repertoire of the pathogen , proteins required for symptom development and those necessary for fungal proliferation can be readily classified , define and then functionally analysed ( ben mbarek et al .\nmethods to define transcriptional networks by chromatin immuno - precipitation coupled to next generation sequencing to define targets genes downstream of transcription factors , will also allow networks of gene expression to be distinguished readily ( soyer et al . ,\nprotein interactions between fungal proteins , but also between fungal proteins that act upon host plant proteins , is also essential , with the ready availability of yeast two - hybrid libraries and associated bespoke protocols to z. tritici ( ma et al . , 2015 ) finally ,\nof course we need to consider the plant host and within this context , transgenic wheat lines expressing organelle - specific markers are already available and being constructed to augment host - pathogen cell biological analysis , while detailed analysis of sources of resistance can guide plant breeding strategies such that durable combinations of resistance genes can be identified and introduced into elite , high yielding commercial wheat cultivars ( brown et al . , 2015 ) .\nwith wider knowledge of the fungal pathogen population and prevailing virulence specificities , should some the ability to breed for exclusion of the most prevalent , prevailing pathotypes of the fungus ( vallet et al . , 2015 ) , providing a direct route to disease control at least in the medium term .\nthe new methods and resources presented in this special issue mean that the z. tritici research community now has , arguably , the same level of research tools as any fungal model system .\nthis is remarkable , because it has happened in a very short period of time in response to an acute need , articulated by growers and the agricultural biotechnology industry .\nan integrated programme has been funded and undertaken to carry out this method development and to begin to apply the newly acquired expertise to understanding this disease .\nmany research questions immediately present themselves . what is the purpose of the morphogenetic plasticity exhibited by z. tritici and how are these dimorphic transitions regulated\nhow is long - distance control of pathogenesis - associated gene expression achieved and how does the fungus perceive and respond to the internal plant tissue environment during infection ? how is sporulation triggered and correctly regulated ? all of these questions can now be addressed and the answers provided will result not only in many of the fungicide targets of the future , but also perhaps to some longer - term strategies for broad spectrum disease control .\nso , to those of you reading this commentary who have never previously considered studying z. tritici , or perhaps not even considered studying a fungal pathogen before , think of the obstacles that have just been removed .", "answer": "septoria blotch of wheat is one of the world s most serious plant diseases , which is difficult to control due to the absence of durable host resistance and the increasing frequency of fungicide - resistance . the ascomycete fungus that causes the disease , zymoseptoria tritici , has been very challenging to study \n . \n this special issue of fungal genetics and biology showcases an integrated approach to method development and the innovation of new molecular tools to study the biology of z. tritici . when considered together \n , these new methods will have a rapid and dramatic effect on our ability to combat this significant disease .", "id": 947} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nIs Lewis acidity in metal dications triggered by solvent shell fluctuations?\n\nPaper sections:\nIntroduction\nIn aqueous solution Lewis acidity is promoted via the hydrolysis reaction (1):
and for metal dications the hydrolysis constant associated with Eq. 1, K h , is defined as (1)
which provides a measure of the acidic strength of water when M 2+ cations are present in aqueous solution. Numerous methods have been proposed in an attempt to correlate the physical properties of metal ions with the value of pK h (= -log K h ); for example plotting against various combination of charge to size ratio (2,3). For closed-shell cations, such as the alkaline earth metals, these correlations often work and suggest that pK h reflects both the underlying electrostatic nature of the M-O bond and the contribution changes in charge density make to the M 2+ -water interaction. However, there are some very notable exceptions to any of the methods that have been proposed, with the most obvious being Sn 2+ , Pb 2+ and Hg 2+ . Some underlying anomalies are obvious; for example, ionic radius of Pb 2+ is comparable to those of both Ca 2+ and Sr 2+ , in aqueous solution the former yields a proton concentration that is two orders of magnitude larger than either of the latter. Similarly, Mg + has a second ionisation energy that is comparable to Pb + , but this time there is almost four orders of magnitude difference in the proton concentrations they generate in aqueous solution. Suggestions as to why Sn 2+ , Pb 2+ and Hg 2+ behave differently, have included: (i) their \"softness\" (4); (ii) changes in coordination number, particularly in the case of Sn 2+ (5,6); and (iii) covalent contributions to the M-OH 2 bond (5). Some attempts to understand and/or quantify hydrolysis have actually omitted Sn 2+ , Pb 2+ and Hg 2+ from the discussion. At a molecular (gas phase) level, there have now been numerous experimental studies demonstrating the ability of alkaline earth metal dications to promote proton release from water molecules. Theoretical interpretation of these (7) and similar events proposed for Sn 2+ , 3 Pb 2+ and Hg 2+ (8) has involved salt bridge structures which have been shown to lower barriers to proton transfer (7,8).
The purpose here is to develop this gas phase analogy of metal ion acidity by interpreting recent experimental data in terms of how shells of solvent molecules might behave when metal cations are in aqueous solution. In a recent series of papers results were present showing how stable gas phase metal dication complexes were with respect to the proton transfer reaction (9,10):
Where X is OH (water), OCH 3 (methanol) or NH 2 (ammonia). In the case of water, Eq. 3 is equivalent to the forward reaction in the hydrolysis step, Eq. 1. For each of the three molecular systems, a value for n, identified as n s , was recorded that corresponded to the minimum number of solvent molecules required to stabilise a dication complex against spontaneous hydrolysis.
For water, measurements for a series of [M(H 2 O) n ] 2+ complexes were performed on the following metal dications: Sr 2+ , Ca 2+ , Mg 2+ , Mn 2+ , Cr 2+ , Cu 2+ , Zn 2+ , Pb 2+ or Sn 2+ , and these results are summarised in Table 1 giving a data set that spans a significant fraction of the available pK h measurements. The metal dications show considerable variation in the values determined for n s ; however, the results obtained for Sn 2+ and Pb 2+ are particularly interesting in that the latter needs at least 11 water molecules to stabilise the ion against gas phase hydrolysis and for Sn 2+ an incredible 26 water molecules are required. Both of these numbers are far in excess of the conventional picture of a stable solvated dication surrounded by just a primary shell of water molecules (5,11), and the results for Sn 2+ suggest that secondary and quite possibly tertiary shells of water are implicated in the ion solvation/stabilisation process (12).
Through the data in Table 1 a link has been proposed between pK h and the critical size at which hydrated gas phase dications undergo spontaneous charge separation (10) (13)(14)(15). Secondly, there is also a more limited link between n s and the Irving-Williams series, namely, Mg 2+ and Ca 2+ < Mn 2+ < Cu 2+ \u2248 Zn 2+ (15,16).
The relationship between n s and pK h works because it reflects instability within each gas phase M 2+ /water unit; however, a more realistic view for the condensed phase might be to consider the numbers of water molecules involved as representing a critical set of solvation shells over which a metal cation has influence. Measurements of the binding energies of water molecules to Ca 2+ have shown that the charge on the metal ion exerts an influence on binding out as far as the third solvation shell (17); however, Table (1) would suggest that the conditions necessary for promoting reaction (3) and those responsible for binding molecules to some of the metal ions have different requirements. Exceptions would appear to be Pb 2+ and Sn 2+ , where promoting instability clearly involves water molecules in the second and third solvation shells. Within an aqueous environment fluctuations in solvent shell occupation 5 in close proximity to a metal ion could cause transient fluctuations in charge density on or in the vicinity of the metal ion, which in turn, might promote proton transfer. This view could be considered as being derived from the Marcus theory of electron transfer, where solvent fluctuation drives the movement of charge (18). A similar approach has been used to describe the mechanism of autoionisation by liquid water, where computer simulations have shown that fluctuations in the concerted motion of atoms can promote charge separation (19). For a metal cation to undergo hydrolysis solvent shell coordination would have to drop below n s , and in the case of Sn 2+ , that could happen very frequently because it would be hard to maintain an extended array of 25 water molecules. At the other extreme, the coordination of Mg 2+ in the first solvation shell would have to drop below four in order for proton release to occur, and because such events are going to be highly improbably, this may account for the very weak Lewis acidity of Mg 2+ .
Many simulations have demonstrated the presence of transient (ps) fluctuations in solvent shell occupation (20)(21)(22)(23) and quantitative evidence of the displacement of water molecules comes from experimental exchange rates recorded for molecules within the first coordination sphere (5,11,24). Using data available for the reaction H 2 O \uf0db H + + OHit can easily be shown that the half life of a water molecule in the liquid phase with respect to autoprotolysis is of the order of 10 4 s (25). Assuming this number scales (very approximately!) with pK h and for a salt concentration of 1 mol l -1 , then following an analysis given by Stillinger (25), estimates of the timescale (\uf074 f ) over which fluctuations of the type discussed above need to occur in order to maintain a particular level of acidity, are summarised in Table 1. The assumption being made here is that the reverse reaction in (1) is diffusion-controlled (~10 11 l mol -1 s -1 ) in the aqueous phase irrespective of the metal cation. This is significant assumption, because unlike water, the ions diffusing together are both 6 positively charged. However, recent kinetic energy releases measurements recorded for reaction (3) give some reflection of the magnitude of the reverse activation barrier as determined by the degree of repulsion between the two separating charges (10). As measured, the gas phase barriers at 1-2 eV are clearly too large to be surmounted under thermal conditions; however, for ion encounters taking place in water these values will drop by a factor of ~ 80, which brings even the largest value down to < 2 kT. There is also a systematic decline in energy release as the complexes increase in size, and this can be attributed to a gradual increase in separation between the MOH + unit and the position from which the solvated proton is released (10). For every factor of 10 drop in the value of the association rate coefficient, \uf074 f will increase by the same amount. In effect, the equilibrium shifts to the right and therefore fewer fluctuations are needed to maintain a specific pK h value.
Also given in Table 1 are exchange times for water molecules in the first coordination sphere; these numbers are not used as part of the calculation, but give an approximate measure of residence time and can place the required timescale for solvent fluctuation in context (5,11,24). Taking, for example Cu 2+ , the exchange time is ~ 10 -10 s, whereas for the reaction Cu 2+ H 2 O \uf0db Cu 2+ OH -+ H + to maintain a pK h of ~7 would require solvation shell fluctuations on a timescale of ~ 10 -4 s. Similarly, to maintain a pK h of ~11 in an aqueous solution of Mg 2+ would require solvent shell fluctuations every ~2.5 s that are sufficient to bring the water molecule occupancy below 4 (n s ); again this number is to be compared with an exchange time of ~ 10 -6 s. The only obvious discrepancy in Table 6 is Sn 2+ ; however, recent computer simulations have given mean residence times for water of the order of 10 -9 s (26,27), which would appear to be more appropriate. However, first-shell exchange times may not always be a good indication of behaviour, since our gas phase results show that the number of solvation shells over which an ion has influence can be sufficiently large that the displacement of solvent molecules in the second and quite possibly the third shell is going to be sufficient to promote hydrolysis. Although solvent exchange times might have been expected to provide a measure of the timescales for the type of transient fluctuation required in solvent occupancy to affect charge density and, hence promote hydrolysis, there is no clear correlation between those quantities and pK h . Probably what is most significant is the result that \uf074 f can be up to six orders of magnitude longer that the exchange or mean residence times for water molecules, which in turn, reflects the rare and rather extreme event required, for example, to displace 3 water molecules from the primary shell of Mg 2+ .
Results presented previously showed evidence of a remarkable correlation between the behaviour of metal dications in the gas phase and properties they exhibit when in aqueous solution. The molecular perspective afforded by this study has made it possible to offer a model of Lewis acidity in terms of an assembly of solvent molecules over which a metal ion has influence when in solution, and that fluctuations in the number of molecules within this grouping can promote Lewis acidity.
", "answer": "The ability of metal ions to generate protons in aqueous solution is of fundamental significance to many processes in chemistry and biochemistry. Numerous attempts have been made to categorise the event in a way that reflects the physical properties of the ions involved; however, several metal ions, including Pb(II) and Sn(II) frequently fail to conform.Here it is proposed that an intrinsic instability exhibited by metal ions associated with water molecules in the gas phase, can offer insight into the ability of the same ions to promote the release of protons in aqueous solution. It has already been shown that the gas phase results overlap with other methods that have traditionally been used to classify the behavior of metal ions in solution, e.g. HASB and the Irving-Williams series. To account for the Lewis acidity of metal ions in solution, a simple model based on fluctuations in solvent shell occupancy is proposed.", "id": 948} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsuperficial leiomyosarcomas are rare malignant tumors that account for only 510% of all soft tissue sarcomas .\nthey can be subdivided into two types according to its primary site of origin : deep subcutaneous and superficial cutaneous types .\nprimary cutaneous leiomyosarcoma ( pcl ) is a rare subtype with few isolated case reports and occasional case series described in the literature .\nwe report the clinical , histopathological and immunohistochemical findings in a 70-year - old male patient with pcl arising in the right leg .\na 70-year - old male patient presented with a painful nodule in the right leg , which had been progressively increasing in size for 4 months . on palpation , an irregular , firm , tender exophytic swelling , measuring 5 cm 5 cm , with overlying skin showing ulceration was noted on the lateral aspect of the lower one third of the right leg [ figure 1a ] .\nhis past history was significant of a trauma and subsequent non - healing ulcer formation at the same site in the right leg .\n( a ) clinical photograph showing an irregular , exophytic swelling , measuring 5 cm 5 cm , with overlying skin showing ulceration on the lateral aspect of the lower one - third of the right leg .\n( c ) gross photograph showing greyish white , solid , homogenous and fleshy cut surface of the irregular tumor mass measuring 5 cm 5 cm 2.5 cm systemic examination and investigations , including complete blood count , fasting blood sugar level , liver function test and renal function test , were within normal limits .\nhepatitis b virus surface antigen and human immunodeficiency virus enzyme - linked immunosorbent assay were non - reactive .\na clinical diagnosis of squamous cell carcinoma was considered and fine needle aspiration cytology of the swelling was requested .\nfine needle aspiration cytology of the same was reported as a spindle cell neoplasm with suspicion of malignancy .\nthe swelling was excised with a 5 cm resection margin and submitted for histopathological examination [ figure 1b ] .\ngross inspection revealed a grey brown , irregular , nodular soft tissue mass , measuring 5 cm 5 cm 2.5 cm and partly covered with skin .\nthe cut surface of the mass was greyish white , solid , homogenous and fleshy [ figure 1c ] .\nthe neoplasm was composed of bundles of elongated spindle cells arranged in interlacing fascicles , with intensely pink , fibrillary cytoplasm and pleomorphic nuclei with coarse irregularly dispersed chromatin .\nmitosis , including atypical , amounting to 22 mitotic figures per 10 high power fields and multinucleate tumor giant cells , was evident .\n( a ) light microscopy revealed a dermal neoplasm with extension into the subcutaneous tissue ( h & e , 40 ) .\n( b ) neoplasm composed of interlacing fascicles of elongated spindle cells ( h & e , 100 ) .\n( c ) tumor cells are spindle shaped with intensely pink , fibrillary cytoplasm and pleomorphic hyperchromatic nuclei frequently exhibiting atypical mitosis ( black arrow ) ( h & e , 400 ) .\n( d ) tumor cells with markedly pleomorphic nuclei and multinucleate tumor giant cell ( inset ) ( h & e , 400 ) a provisional diagnosis of spindle cell malignant neoplasm of the skin , which typically includes a host of diagnostic possibility , namely fibrosarcoma , leiomyosarcoma , malignant peripheral nerve sheath tumor , monophasic synovial sarcoma , malignant fibrous histiocytoma and spindle cell variant of squamous cell carcinoma , was considered and immunohistochemistry was advised for confirmation .\non immunohistochemistry , tumor cells showed strong immunopositivity for vimentin , muscle - specific actin ( msa ) , smooth muscle actin ( sma ) , caldesmon and desmin and negative for pancytokeratin , epithelial membrane antigen ( ema ) , myogenin , cd34 and s-100 protein [ figure 3 ] .\nimmunohistochemical staining : neoplastic cells showing positive immunostaining for ( a ) vimentin ( vimentin , 400 ) , ( b ) caldesmon ( caldesmon , 400 ) , ( c ) muscle - specific actin ( msa , 400 ) and ( d ) smooth muscle actin ( sma , 400 ) based on the immunophenotypic features , a final diagnosis of pcl was rendered .\nthe patient is currently on periodic follow - up since 1 year and no recurrence or metastasis has been identified so far .\nalthough pcl most commonly arises in the extremities , particularly hair bearing surfaces , it may occur at any anatomic site on the body .\nmost case series described in the literature report a predilection for the middle aged to elderly male . in a large case series reported by fields and helwig ,\n95% of the patients with pcl presented with a solitary nodule with a median size of 1.8 cm at presentation .\npain was reported by 24% of their patients at presentation , whereas pain could be elicited on pressure in an additional 27% of the patients .\nhistologically , pcl is characterized by a poorly circumscribed proliferation of interwoven fascicles of spindle shaped atypical myomatous cells that merge with a collagenous stroma .\nmitosis , equivalent to one or more per 10 high - power fields , high cellularity and bizarre myomatous cells are the generally accepted criteria for malignancy .\ndescribed two growth patterns : a nodular pattern characterized by high cellularity , prominent nuclear atypia , conspicuous mitosis and a diffuse pattern that is less cellular , well differentiated and inconspicuous mitosis .\nmorphologic differential diagnosis includes a galaxy of other malignant spindle cell neoplasms , namely desmoplastic malignant melanoma , spindle cell synovial sarcoma , spindle cell angiosarcoma , fibrosarcoma , malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor .\ncutaneous leiomyosarcoma often exhibit immunophenotypic polymorphism , thereby mandating the use of a large panel of antibodies .\nhowever , none of these markers is absolutely specific for smooth muscle , and positivity for two of these markers is more supportive of leiomyosarcoma .\njensen et al . identified several poor prognostic factors , namely tumor size 5 cm , acral location , deep localization with fascia involvement and high histological grade .\ncutaneous leiomyosarcomas have fewer incidences of local recurrence ( 30 - 50% ) and negligible potential for distant metastases ( 010% ) . in contrast\n, subcutaneous leiomyosarcomas may develop local recurrence in about 4060% and distant metastasis in 2060% of patients .\na wide local excision with a 35 cm margin is usually an effective treatment for pcl .\n, pcl is a rare entity that must be borne in mind when encountered with a malignant spindle cell neoplasm of the skin and usually requires a panel of immunohistochemical markers to distinguish it from other cutaneous malignancies with spindle cell morphology .", "answer": "primary cutaneous leiomyosarcoma ( pcl ) is an exceedingly uncommon malignant superficial soft tissue sarcoma with a predilection for middle - aged to elderly male . \n morphologic differential diagnosis includes a host of other malignant spindle cell neoplasms , thereby necessitating the use of a panel of immunohistochemical markers to arrive at a definitive diagnosis . \n we report a case of pcl arising in the right leg of a 70-year - old male .", "id": 949} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nduring the early years that followed the discovery of x - ray , radiographers were unintentionally , incautious when dealing with it because of its unknown biological harmful effects .\nmany cases of cancer , sterility and death due to x - ray / radiation toxicity were documented during the early years of the 20 century .\nfor example , in 1907 , 6 out of 11 cases with x - ray - induced caners died .\nmoreover , many early workers in the field of dentistry suffered from radiation - induced ulceration , dermatitis and malignant tumors in their fingers . with strict compliance to the radiation protection guidelines , issued by the international commission on radiological protection ( icrp ) , diagnostic radiography is considered a safe practice .\n, no other reports addressing the disastrous effects of x - ray radiation have been documented in the literature since 1960s . the present report , however , documents a case of thumbs carcinoma of a dental radiographer due to his neglect of radiation protection guidelines .\nin august 2010 , a 49-year - old male working as a dental radiographer , lost his distal phalanges of both thumbs as a result of development of squamous cell carcinoma , due to neglect of the guidelines of protection related to x - ray imaging .\nhe was appointed in 1994 by the radiology division , primarily as an in - charge clerk within the oral medicine department ( faculty of dentistry , damascus university ) . as a school graduate with an intermediate certificate ,\nhis main task was merely to monitor the radiographic equipment . given that there was only one radiographic technician at that time , it was decided in 1995 to train him on how to use the dental x - ray machines and how to radiograph patients .\nhe was warned about the radiation risks and thoroughly educated on the appropriate protection standards .\non the other hand , he was accustomed to handling the periapical films with his thumb fingers . in 2003\nalthough it was asymptomatic , he considered it as a traumatic ulcer and hence willingly neglected it for a period , which under normal circumstances would be considerably enough for such an ulcer to heal .\nsubsequently he then experimented with various courses of local and systemic antibiotic , but the ulcer did not show any signs of healing . based on his judgment\n, it was asymptomatic and unprogressive , and accordingly he perceived to be a normal exfoliation , the result of his long - term handling of chemical processing solutions . in august 2010\n( after 15 years of handling dental x - ray ) , he noticed a discharge oozing from his right thumb . by that time , he also took notice of a similar ulcer in his left thumb .\nhe consulted the professors in the department who in turn referred him to a general surgeon . on plane hand radiographs ,\nan erosion of the distal phalanges of both thumbs was clearly evident [ figures 1 and 2 ] .\nconsequently , the surgeon planned to excise the discharging ulcerative lesion of the right thumb and to submit it for histopathological diagnosis , which clearly revealed squamous cell carcinoma grade ii [ figure 3 ] . based on such a diagnosis ,\nthe surgeon decided to excise the distal phalanges of both thumbs with tumor free - margins [ figure 4 ] .\nout of ethical consideration , the radiographer was well - informed about the intent to publish his case and hereby he signed an informed consent .\nplane hand radiograph reveals bone erosion in the right thumbs distal phalanges plane hand radiograph reveals bone erosion in the left thumbs distal phalanges histopathologic microphotographs reveal squamous cell carcinoma ( [ a ] 40 and [ b ] 100 )\nearly x - ray machines needed to be set and repeatedly adjusted . to achieve this\n, radiographers would place their hands between the actively radiating tube and the film plate to check if the apparatus was functioning and that it was well focused on the film . by practicing this for 12 years , dr . kells\nwas the first victim of dental x - ray radiation with numerous cancerous tumors on his fingers . by that time , the icrp published guidelines for radiation protection that have been updated from time to time . in syria ,\nthe atomic energy commission adopted these guidelines and has since strictly emphasized the importance of their application by public and private institutions .\none of the guidelines clearly states that the film should never be hand held by a member of the dental practice staff , even for patients with special needs . holding periapical films in the patient 's mouth is still practiced in modern dentistry , but , fortunately , is not common .\nsixty per cent of australian dentists never do this , but 25% will do so less than once every month , and 1.5% might do so more than 10 times a month .\nthe radiation - risk is the function of the radiation dose which is expressed as an effective dose .\nthe national commission for radiation protection in the united states reports that the mean effective dose received by dental workers is 0.2 msv / year .\nsimilarly , the national radiological protection board , in the uk estimates a mean level of < 0.1 msv / year . in dose limit terms for workers ,\nthe current effective dose limit is 100 msv in any consecutive 5 years with a maximum of 50 msv in any year .\nthese limits are based on guidance from the icrp , with the effective dose limit being set at a level at which the stochastic risk is considered to be at the limit of acceptability .\nthe probability of radiation - induced stochastic effects for the whole population is 7.3 10 /sv . the working load in the radiology division within the faculty ranges between 100 and 150 patients a day .\nhence , the radiographer in the current report received a fraction of about 600900 sv / day ; 13.219.8 msv / month ; 158237 msv / year and 2.43.6 sv in 15 years .\noverall , he was at a greater risk of getting a stochastic effect by 2.43.6 times compared to the whole population , as the probability of radiation - induced stochastic effect for this case ranges from 18 10 to 26 10 /sv .\nsome authorities claim that any dose of radiation has the potential to induce malignant changes , and there is no threshold dose below which radiation is predictably safe .\nthe risk of induction of fatal cancer or serious hereditary ill - health from dental intra - oral radiography was estimated to be 1 in 10 million ( 10 ) per exposure .\nthis increased the risk of inducing fatal cancer or serious hereditary ill - health to 46 in 100 ( 10 ) .\nhowever , the risk - estimates depend on the shape and length of the collimator or position indicating devices ( pids ) .\nthe short and pointed cones with closed - end , such as that which had been used by the radiographer in this report for 13 years ( fiad , dr 554 , italy ) , have the greatest probability of a stochastic effect ( 1 in 26 10 ) in comparison to the rectangular or round ones .\nthe latter , which are open - ended and have been used for the last 2 years of the radiographer 's work ( ardet s.r.l buccinasco [ mi ] orix 70 , italy ) , have a probability of a stochastic effect ranging from 1 in 4.6 10 to 1 in 23 10 according to the length .\noverall , the shielded open - end pids , both round and rectangular in shape , have become more widely used during the past 40 years because of the reported decrease in patient exposure that is achieved . in general ,\ndental radiography has a little dose and risk for the individual patient and dental workers provided that the principles of protection are applied ; it is less dangerous in comparison to a few days of natural background radiation to which we are all constantly exposed .\ndental radiography doses and risks are minimal unless dealt without being cautious , which is the case of the radiographer presented here .", "answer": "dealing with diagnostic x - ray radiation may result in serious health problems , unless protection guidelines are followed . \n this became prevalent immediately a decade following the invention of x - ray radiation , where it had not been known that the accumulative exposure to x - ray radiation may carry huge health hazards . \n the reoccurrence of various fatal cancer cases compelled the concerned health authorities to develop safety standards to be followed by all x - ray clinics and technicians worldwide . \n this report documents the clinical case of a dental radiographer , who developed thumbs carcinoma after 15 years of practicing the profession , most likely due to his neglect of the x - ray radiation protection guidelines .", "id": 950} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe typical clinical presentation of poi is pain in the right side of the abdomen , and this may lead to a misdiagnosis of acute appendicitis or cholecystitis . here , we present a case of poi , with pain in the left lower quadrant .\na 50-year - old woman admitted to the emergency room with a history of worsening abdominal pain for 5 days .\nthe pain began in the upper abdomen and later localized to the left lower quadrant , and the pain intensity exacerbated with activities .\nthe pain was sharp and constant in nature without nausea or vomiting . on physical examination , the patient was febrile with a temperature of 38.1c and had severe left lower quadrant tenderness and abdominal rigidity .\nthe previous history included an open ectopic pregnancy surgery in 1996 , and no atrial fibrillation , no venous thrombosis , no contraceptive , or aspirin usage .\nthe laboratory test showed white blood cell 9.71 10/l , d - dimer 1.58 mg / l , and no other abnormalities .\nan abdominal computed tomography ( ct ) was performed and showed a left ovarian cyst measuring 6.0 cm 4.5 cm with no other remarkable findings [ figure 1a ] .\nafter about 1 day , the patient complained of worsening abdominal pain and absence of passage of feces and gas .\n( a ) axial image showed a left ovarian cyst measuring 6.0 cm 4.5 cm .\nmedian sagittal section showed an increased fat - density mass consequently , we performed laparoscopic exploration . during the procedure , we found a segment of congested necrotic omentum adhering to the abdominal wall with a segment of small intestine [ figure 2a ] , bloody ascites ( 200 ml ) accumulated in the abdominal cavity [ figure 2b ] , and an ovarian cyst measuring 6.0 cm 4.5 cm in pelvic cavity [ figure 2c ] .\nwe resected the nonviable omental segment , and the gynecologist removed the ovarian cyst using laparoscopic procedures .\n( b ) a dark purple mass on the left side in the lower part of the omentum and bloody ascites in the left abdomen . ( c )\na huge ovarian cyst by reanalyzing the preoperative ct , a segmental fat mass with an increased density was noted in the left lower quadrant which was consistent with the intraoperative findings [ figure 1b ] .\nfinal pathological examination revealed hemorrhagic infiltrations , thrombosis of the tissue , acute inflammatory cellular infiltrate , and fibrinoid necrosis , and poi was diagnosed [ figure 3 ] .\nhistological examination of the resected nonviable omentum revealed hemorrhagic infiltrations , thrombosis of the tissue , acute inflammatory cellular infiltrate , and fibrinoid necrosis\nup till now , only a few hundred cases have been published in the english literature .\nsusceptible factors include ( 1 ) anatomic malformations such as a bifid or accessory omentum causing the spontaneous torsion , ( 2 ) sudden movement , violent exercise , and hyperperistalsis , and ( 3 ) obesity .\nmost authors support the hypothesis that it is associated with an anomalous and fragile blood supply of the right lower portion of the omentum , which is consequently susceptible to infarction .\nthus , 90% of all the cases have initial pain in the right side of the abdomen .\nour patient had pain in the left lower quadrant , so we did not include poi in the differential diagnosis spectrum .\npoi has no early specific signs and is often characterized by progressive , persistent abdominal pain .\nclinical features include unspecific gastrointestinal symptoms , slightly febrile , and mild leukocytosis . in the present case ,\nd - dimer can be used as an objective parameter in the differential diagnosis of poi as it is used in other thromboembolic diseases .\nthe most diagnostic finding is an ill - defined heterogeneous fat density with surrounding inflammatory changes . by retrospective reanalysis of the preoperative ct in this study ,\nultrasound is specific but not sensitive for diagnosing poi ; suspected imaging features include hyperechoic , incompressible , ovoid mass , and detectable in < 50% of cases , even when reviewed retrospectively .\ntwo patients underwent surgery , one because of the absence of spontaneous regression and the other because of extremely severe clinical symptoms . in the other four patients ,\nconservative management was given and successful . if a confirmed diagnosis of poi can be made with the typical clinical signs and imaging studies , conservative treatment is the first - line therapy during the first 2448 h while resuscitation and antibiotics are initiated .\nhowever , if the diagnosis is in doubt or if conservative treatment fails , laparoscopy should be performed without delay . as in the present case ,\nthe pain was not relieved after conservative treatment for 24 h. intestinal obstruction occurred as a segment of small intestine adhered to the abdominal wall .\npoi should be considered in the differential diagnosis of any patient presenting with acute abdominal pain .\nlaparoscopic exploration should be performed if new symptoms occur or do not relieve within 2448 h. there are no conflicts of interest .", "answer": "primary omental infarction ( poi ) is a rare cause of acute abdomen . \n most patients have aggravating abdominal pain without gastrointestinal symptoms . here , we report a case of omental infarction in a 50-year - old woman , who had left abdominal pain and intestinal obstruction . preoperative computed tomography ( ct ) of the abdomen showed a left ovarian cyst measuring 6.0 cm 4.5 cm but otherwise seemed normal initially . \n the white blood cell count was 9.71 109/l , and d - dimer was 1.58 mg / l . \n laparoscopic exploration was performed 1 day after admission because of peritonitis and intestinal obstruction . during the exploration \n , a segment of congested necrotic omentum was found adhering to the abdominal wall with a segment of small intestine . \n bloody ascites was also observed in the abdominal cavity . \n we resected the nonviable segmental omentum , and the ovarian cyst was removed by the gynecologist using laparoscopic procedures . \n final pathological findings confirmed poi . while reanalyzing the preoperative ct , a segmental fat mass with an increased density \n was noted in the left lower quadrant , which was consistent with the intraoperative view 6 days after surgery . \n the patient recovered uneventfully and was discharged .", "id": 951} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsix hundred officers were recruited from the police departments of new york , ny , and oakland and san jose , calif , usa . fifty - two percent of the sample was caucasian .\nthe mean age was 36,50 years ( standard deviation [ sd])=6.96 ) . years in the police force everaged 12.37 ( sd=6.78 ) .\nnumber of exposure to critical incidents ranged from 2 to 670 ( mean [ m]= 171.27 , sd=130.93).the incident selected for completing the questionnaires had occured on average 6.50 ( sd= 5.11 ) years ago .\nthe peritraumatic distress scale ( pds ) was used to assess emotional , cognitive , and physical reactions occuring during a critical incident and immediatly after .\ndissociation at the time of the incident was measured with the peritraumatic dissociative experience questionnaire ( pdeq).the impact of event scale - revised ( ies - r ) was used to measure ptsd symptoms in the last 7 days .\nthe mississippi scale ( mcs ) was used to measure ptsd and associated symptoms since the critical incident . \n \nwe conducted a cronbach alpha reliability analysis and an oblique principal factor analysis with promax rotation on the items of the pds .\ntwo series of hierarchical multiple regression analyses were conducted using sociodemographics ( gender , ethnicity , years of service ) , exposure , the pdeq and pds as predictors of either the mcs or the ies - r\nsix hundred officers were recruited from the police departments of new york , ny , and oakland and san jose , calif , usa . fifty - two percent of the sample was caucasian .\nthe mean age was 36,50 years ( standard deviation [ sd])=6.96 ) . years in the police force everaged 12.37 ( sd=6.78 ) .\nnumber of exposure to critical incidents ranged from 2 to 670 ( mean [ m]= 171.27 , sd=130.93).the incident selected for completing the questionnaires had occured on average 6.50 ( sd= 5.11 ) years ago .\nthe peritraumatic distress scale ( pds ) was used to assess emotional , cognitive , and physical reactions occuring during a critical incident and immediatly after .\ndissociation at the time of the incident was measured with the peritraumatic dissociative experience questionnaire ( pdeq).the impact of event scale - revised ( ies - r ) was used to measure ptsd symptoms in the last 7 days .\nthe mississippi scale ( mcs ) was used to measure ptsd and associated symptoms since the critical incident . \n\nwe conducted a cronbach alpha reliability analysis and an oblique principal factor analysis with promax rotation on the items of the pds .\ntwo series of hierarchical multiple regression analyses were conducted using sociodemographics ( gender , ethnicity , years of service ) , exposure , the pdeq and pds as predictors of either the mcs or the ies - r\nthe pds scores ranged from 0.10 to 3.57 and the mean was 1.37 ( sd=0.56 ) .\nthe scale was internally consistent ( =0.80 ) and showed strong convergent validity with the pdeq , r(599)=0.55 , p<0.001 .\nthe pds factor solution is presented in table i items defining factor 1 included dysphoric emotions such as helplessness , sadness and grief , frustration and anger , and horror .\nfactor 2 was mostly defined by items related to loss of safety and arousal , such as being afraid , thinking one might die , and having intense bodily reactions ( sweating , shaking , heart - pounding ) .\nitems loading on factor 3 were related to the loss of positive beliefs about the self and others , such as thinking that one had done all he or she could during the critical incident , not felling prepared by one 's experience , and not believing tha others understood .\nwe labeled the factors negative emotions , perceived life threat and bodily arousal , and appraisal .\nthe sum of communality estimates was 7.58 , explaining 38% of the communality estimates was 7.58 , explaining 38% of the total variance and 93% of trace .\nintercorrelations among the pds factors were low , ranging from -0.25 to 0.12 ( p<0.05 ) .\nthe low pds factor intercorrelation coupled with correlations of 0.17 to 0.42 ( p<0.001 ) with the outcome measures ( ies - r and mcs ) suggest that various forms of peritraumatic distress , as captured by the pds , can lead to the development of ptsd symptoms .\ntwo stepwise regression analyses ( not fully reported here ) were conducted . in predicting the mcs and ies - r ,\nthe pdeq , entered in the second step , explained 20% and 16% of unique variance on the mcs and ies - r , respectively . entering the pds in step 3 explained 11% and 8% unique variance on the mcs and ies - r , respectively .\nwe repeated this set of analyses with the inclusion order of the pdeq and pds reversed .\nentered in the second step , the pds explained 29% and 17% of unique variance on the mcs and ies - r , respectively . entered in the third step , the pdeq explained 3% of unique variance on both the mcs and the ies - r .\nthe items and factors of the pds provide insight as to what some of the salient peritraumatic dimensions may be , in addition to peritraumatic dissociation . in this study ,\nthe pds explained a significant amount of variance over and above peritraumatic dissociation which is currently considered among the mos powerful predictors of ptsd symptoms .\ntest - retest data for the pds is currently being gathered as well as data from individuals not working in the police . in future\n, it would be useful to investigate prospectively the power of the pds in predicting ptsd diagnosis rather than symptoms , as well as other trauma - related disorders .", "answer": "posttraumatic stress disorder ( ptsd ) occurs when significant intrusion , avoidance , and hyperarousal symptoms are manifest for at least 1 month following exposure to a traumatic event , with at least 1 month following exposure to a traumatic event , with at least 1 month elapsed betwenn the event and the diagnossis ( diagnostic and statistical manual of mental disorders , 4th edition , 1994 [ dsm - iv]).1 however , such symptoms are not necessarily manifest in the immediate aftermath of the trauman,2 nor does their intial presence strongly predict who will develop ptsd.3 one immediate response to trauma which has been convicingly linked to ptsd symptoms is peritraumatic dissociation.4 in this poster , we briefly introduce a new scale assessing immediate responses distinct from peritraumatic dissociation , and we examine its power to predict ptsd symptoms .", "id": 952} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is very important to distinguish m. abscessus from other nontubercular mycobacteria ( ntm ) as antimycobacterial therapy is significantly more complex .\na 53-year - old male patient from gujarat ( india ) , with a history of hypertension , diabetes mellitus , hypothyroidism , and a stable dilated cardiomyopathy was shifted to our hospital with a prolonged pyrexia , which had remained undiagnosed and unresponsive to standard antimicrobial treatment .\na coronary angiography had been performed 8 weeks earlier , which showed normal coronary anatomy .\nthree weeks following the angiography , the patient developed moderate- to high - grade fever for which standard investigations , routine blood cultures , and imaging were performed and were inconclusive .\nhe was transferred to our care 6 weeks into his febrile illness with no clear diagnosis . on examination ,\nthe patient was febrile , toxic , and had an early diastolic murmur in the aortic area .\nthe investigations revealed hemoglobin 8.3 g / dl , white blood cells 9200 cells / mm , platelets 2,23,000/mm , serum creatinine level 2.2 mg / dl , and erythrocyte sedimentation rate 88 mm / h .\nurine analysis showed 3 - 5 red blood cells ( rbcs)/high power field ( hpf ) and a raised 24-h urine protein of 1527 mg/24 h was also noted . on ultrasonography ,\nthere was mild hepatosplenomegaly , but there was no evidence of focal lesions in the spleen or liver .\nchest roentgenogram revealed mildly prominent pulmonary vasculature with cardiomegaly but no significant lung parenchymal pathology .\nthe two - dimensional echocardiography ( 2d echo ) done at previous hospital showed left ventricular ejection fraction ( lvef ) of 30% , normal heart valves , and global hypokinesia .\na repeat 2d echo at our center showed an evidence of mild aortic regurgitation with three discrete small mobile vegetations on the left and right coronary cusps of the aortic valve .\nchoroidal infiltrates as a stigmata of infective emboli were noted , but there was no evidence of embolization to skin or any other organ .\ndouble stranded antibody ( anti - dsdna ) , and anti nucleophilic cytoplasmic antibodies ( anti - anca ) were negative and complement levels ( c3 and c4 ) were within the normal range .\nthe patient was treated for heart failure and was started on ceftriaxone at a dose of 1 g twice daily intravenously as empirical treatment for infective endocarditis .\nbactec myco / f lytic medium was then used , which demonstrated the rapidly growing organisms as ntm .\nlinezolid and clarithromycin were empirically added while awaiting the sensitivity and speciation of the ntm .\nmeanwhile , species identification using the line probe assay technique revealed the organism to be m. abscessus and drug sensitivities were subsequently obtained .\nthe organism was found to be sensitive to amikacin , clarithromycin , linezolid , and tobramycin , with intermediate sensitivity to cefoxitin but was found to be resistant to doxycycline , imipenem , cefepime , ceftriaxone , minocycline , and amox clavulanic acid .\nthe two antibiotics ( linezolid and clarithromycin ) were continued and the other sensitive drugs isoniazid , ethambutol , and cefoxitin were added to the treatment regimen .\nthe patient defervesced for the first time after 7 weeks of continuous fever 1 week into the above treatment .\nlinezolid was withheld for 10 days in view of significant bone marrow suppression but was later reinstituted in lower doses .\nafter 3 weeks of therapy with a combination of five antibiotics , the creatinine stabilized at 2.6 mg / dl having previously reached a peak of 3.6 mg / dl .\nthe valvular vegetations , however , were present and blood cultures still grew the same mycobacteria despite the patient having defervesced .\naortic valve replacement surgery was considered but was withheld in view of multiple comorbidities and patient 's reluctance to undergo any procedure .\na repeat 2d echo at 4 weeks post treatment showed no change in the vegetation size and the patient was discharged on request on all five antimycobacterial antibiotics .\nsubsequently , the patient developed worsening cardiac failure and died of pulmonary edema and renal dysfunction despite aggressive medical management in a local intensive care unit .\npostprocedure mycobacterial infections have been often reported , especially in india where glutaraldehyde is used as a sterilizing solution for surgical and other equipments .\nrisk factors for bacteremia following catheterization include obesity , duration of the procedure , the number of balloons used , and the number of skin punctures performed .\ninfections complicating coronary angiography include sepsis , endocarditis , suppurative pancarditis , stent infection , septic arthritis , epidural abscess , necrotizing fasciitis , and groin wound infection .\nthe most common causative organism of bacteremia following cardiac catheterization is staphylococcus aureus , particularly in the obese .\nnative valve endocarditis with ntm such as m. abscessus is rare and often missed without appropriate blood cultures . in cases of postprocedure endocarditis ,\nearly diagnosis and prolonged combination therapy are obligatory to minimize mortality , as m. abscessus is inherently resistant to multiple antibiotics .\nalthough there are no specific drug protocols for treatment of pulmonary m. abscessus disease , a macrolide - based regimen is often used combined with surgical debridement for successful therapy .\nevidence - based management for other nonpulmonary diseases and specifically for m. abscessus endocarditis is lacking due to sheer rarity of the condition and treatment is based on in vitro drug susceptibility .\ntypically , antibiotics with maximum in vitro activity against m. abscessus isolates include amikacin , clarithromycin , tigecycline , and cefoxitin . to a lesser extent ,\ncombination therapy is mandatory and should be administered for at least 2 - 4 months .\ntigecycline and linezolid are newer antibiotics with efficacy against m. abscessus and the recommended treatment length with these drugs is 6 - 12 months . among the carbapenems ,\nclarithromycin and linezolid were used in combination as aminoglycosides were contraindicated due to renal failure .\nthe cause of the raised creatinine was thought to be multifactorial , secondary to diabetic nephropathy , hypertension , and congestive cardiac failure .\nthe possibility of septic emboli causing nephritis seems low owing to only 3 - 5 rbcs / hpf in urine .\nisoniazid and ethambutol were added as standard antituberculous therapy with the hope of some benefit in such a desperate situation .\nm. abscessus infection is not always considered a medically curable condition , but prolonged antibiotic therapy may result in chronic suppression of the disease . in vitro drug susceptibility patterns do not always correlate with clinical responses and measurements of minimum inhibitory concentrations of antibiotics do not always predict their therapeutic effects .\nendocarditis caused by m. abscessus generally has a very poor prognosis despite combination antimicrobial therapy , as only two of the 10 documented cases described in the literature have survived after treatment .\nsurgical intervention to replace the infected valve would have been worth attempting if the patient had been willing . however , in view of the dismal treatment outcomes shown by previous studies , it remains uncertain if early institution of appropriate therapy or valve replacement would have altered the ultimately fatal outcome with this pathogen .\nnosocomial infection control needs to be strengthened particularly at smaller centres where complex interventions are increasingly being conducted .", "answer": "mycobacterium abscessus is an unusual cause of infection in immunocompetent patients . \n the intrinsic and acquired resistance of this organism to multiple antibiotics is a major issue in planning treatment regimens . \n we report a case of m. abscessus endocarditis of the native aortic valve in an immunocompetent patient following coronary angiography with a fatal outcome . \n the case highlights an unfortunate intervention related nosocomial infection and the difficulties in chemotherapeutic options for this organism , particularly in the presence of renal failure .", "id": 953} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe chromosome number in the donkey ( equus asinus ) is 2n= 62 , but 2n= 64 in the horse ( equus caballus ) .\nin fact , a certain level of bidirectional sex genome compatibility does exist : when a male donkey and a female horse mate , they produce a mule , and when a stallion mates with a female donkey , a hinny is produced .\nboth are usually sterile , but in some cases a certain level of genome compatibility is found and female mules get pregnant , although embryo loss is quite frequent . among the different dna sequences making up a eukaryotic genome , highly repetitive dna sequences are considered good evolutionary markers , due to their capacity to change rapidly as compared to single gene sequences . these dnas are commonly associated with satellite dna fractions ( sat - dna ) and are usually localized in constitutive heterochromatin regions . their ability to rapidly alter their base composition can produce rapid divergence in equivalent chromosome domains .\nthis divergence can easily be observed , both within species and among closely related species .\nthis is the case , for example , with alphoid dna sequences in humans and other primates . during the last few years\n, our research group has developed a method , whole comparative genomic hybridization ( w - cgh ) , which allows the identification of chromosomal polymorphisms related to sat - dnas localized in constitutive heterochromatin .\nw - cgh acts by detecting polymorphisms on the basis of competition between two different genomic dnas in the experimental conditions of in situ hybridization , without subtraction of highly repetitive dna sequences .\nthis technique has been used in several related species and/or individuals or populations belonging to the same species .\nthese differences are easily assessed when the y chromosome in boar is targeted . on the contrary , this differentiation was not noticeable when different ram breeds were compared . given the genetically - imposed lack of homologous recombination on y chromosomes , the rate of sequence evolution within these chromosomes is usually higher than that in autosomes .\nfurthermore , the y chromosome tends to be unusually rich in repetitive dnas , due to both transposable elements and tandem arrays of sat - dna sequences .\nthe aim of this preliminary work was to characterize donkey and horse y chromosome highly repetitive dna sequences , to understand resemblances and differences between the two y chromosomes isolated approximately 2 my ago .\nwhole genomic dna was obtained from the peripheral blood of one stallion and one male donkey .\nthe stallion was a pure spanish breed and the donkey a spanish breed ( zamorano - leons ) in danger of extinction .\nperipheral blood lymphocytes were extracted and cultured for 72h in rpmi 1640 ( gibco , invitrogen corporation , carlsbad , ca , usa ) . this medium was supplemented with 1.5% phytohaemagglutinin , 10% fetal calf serum and antibiotics .\nchromosomes were obtained using cells arrested at metaphase with colcemid ( 10 mg / ml ) for 90 minutes .\nchromosome slides were prepared by exposing the cell suspension to 0.075 m kcl for 20 minutes and rapidly fixing it in fresh fixative ( methanol - acetic 3:1 ) . to obtain metaphase cells ,\nfixed lymphocytes were spread onto clean slides and allowed to dry . for the w - cgh experiment , stallion and donkey dnas\nthe final concentration of each dna sample was carefully measured using a dna - spectrophotometer ( amersham - pharmacia biotech , piscataway , nj , usa ) .\ntwo dna samples of equivalent concentration were labelled with biotin-14-dutp ( h : horse ) and digoxigenin-11-dutp ( d : donkey ) , employing a commercial nick translation kit ( roche diagnostics corporation , indianapolis , in , usa ) . after dna labelling ,\nprobe size fragments were tested to be in the range of 6002000 bp in a 1% agarose gel .\nboth dna probes were mixed at equal concentrations and the resulting mixed probe was precipitated with ethanol .\nafter air drying , the probe was dissolved in hybridization buffer ( 50% formamide-2xssc/10% dextran sulphate-2xssc , vol / vol ; ph 7 ) to a final concentration of 20 ng/l , denatured at 70c for 10 minutes and placed on ice for 5 minutes . for fish , metaphase slides\nwere incubated in 2xssc at 37c for 60 minutes and dehydrated in 70% , 85% and 100% ethanol .\nafter air drying , slides were denatured in 70% formamide/ 2xssc ph 7 at 70c for 2 minutes and dehydrated again . in this experimental approach ,\nthe dna probe was applied to the slides and hybridized at 37c in a moist chamber overnight .\nafter hybridization , slides were washed in 50% formamide at 42c for 15 minutes and in 2xssc at 37c for 8 minutes . a non - specific antibody blocking solution [ bsa 10% ( wt / vol)/tween 20 , 0.05% ( vol / vol)/ 2xssc , ph 7 ] was applied for 5 minutes at 37c .\nslides were then incubated for 25 minutes at 37c in the antibody solution , with a single layer of fitc - avidin and rhodamine anti - digoxigenin antibodies ( appligene- oncor , illkirch , france ) , for simultaneous localization of the two probes in green ( g ) and red ( r ) , respectively ( stallion probe + donkey probe ) .\nfish experiment samples were counterstained with dapi ( 4 , 6-diamidino-2-phenylindole ) ( 100 ng/l ) .\ndapi counterstaining blocks yellow fluorescence produced by a similar contribution of both dna probes on the chromosome arms , but its use is advisable , as it enhances contrast with constitutive heterochromatin labelling .\nslides were analyzed using a leica dmlb fluorescence microscope equipped with a charge - coupled device camera ( leica dfc350 fx , leica microsystems ) with three independent green , red and blue filters .\nfiles were merged using using adobe - photoshop cs3 ( adobe systems incorporated , usa ) .\nwhen w - cgh was carried out on stallion chromosomes using an equimolar genomic dna probe obtained from horse and donkey , all chromosomes showed varying quantities of green fluorescence in the constitutive heterochromatin of each autosome . this is the result expected , given that the chromosomal strip for dna probe landing was stallion chromosomes . in some autosomes , there was only a green signal ( arrows in figure 1a ) , while in others the green signal co - localized with a red signal ( contribution of expanded dna sequences in donkey ; arrowhead in figure 1a ) . interestingly , after w - cgh , the y chromosome split into three different chromosome domains ( figure 1a ) .\nthis region resembles the chromosome domain related to kinetochore activity , and for this reason was identified as the proper centromeric region ( h - cr ; figure 1b ) .\nh - cr is small as compared to the rest of the y chromosome and , in this case , showed only intense green fluorescence . additionally , an interstitial , highly expanded and pericentromeric region ( h - pr ; figure 1b ) , showing red fluorescence , was present . finally , a distal region ( h - dr ; figure 1b ) which fluoresces in blue because of the counterstaining effect was observed .\nh - dr before dapi counterstaining showed yellow fluorescence due to the equivalent contribution of both dna probes . in the w - cgh environment , this is the normal staining response in chromosomal arms . in short ,\nthe y chromosome in this stallion is principally compartmentalized in three different chromosome domains , where h - cr is mainly constructed with specific dna families from the horse , while h - pr reveals a massive presence of highly - expanded donkey dna sequences which are also present in the stallion , although at lower intensity .\nthis chromosome compartmentalization evident in the stallion chromosome is very similar to the gtg - banded y chromosome in donkey , as represented by raudsepp et al . \n\nfigure 1panel 1a shows metaphase chromosomes of stallion after hybridization with an equimolar genomic dna probe obtained using whole stallion ( labelled in green ) and donkey genomic dna ( labelled in red ) .\nnote that all autosomes reveal fish signal corresponding to the stallion dna labelling colour ( green , see standard arrows ) , while red ( donkey ) is present in some autosomes ( arrowhead ) and the y chromosome . a diagram showing the possible expansion and divergence among centromeric and pericentromeric dna subfamilies\npanel 1a shows metaphase chromosomes of stallion after hybridization with an equimolar genomic dna probe obtained using whole stallion ( labelled in green ) and donkey genomic dna\nnote that all autosomes reveal fish signal corresponding to the stallion dna labelling colour ( green , see standard arrows ) , while red ( donkey ) is present in some autosomes ( arrowhead ) and the y chromosome . a diagram showing the possible expansion and divergence among centromeric and pericentromeric dna subfamilies\nresults obtained in the present preliminary study clearly show that the stallion and donkey still share some highly repetitive dna families , although the expansion level of specific sub - chromosomal domains varies and is characteristic for each species .\nthis tendency is observed in most autosomes , but in the particular case of the stallion y - chromosome , some peculiar dna arrangements ( h - pr ) are conserved , while appearing to have greatly expanded during the evolution of the donkey y - chromosome ( d - pr ; figure 1b ) .\nan alternative explanation is that dna arrangements in h - pr , equivalent to those in d - pr , were partially lost during evolutionary processes regarding the y - chromosome . in both cases\n, the absence of legitimate recombination would facilitate this process of differential dna expansion or contraction .\nthe results showing differential expansion of highly repetitive satellite dna families are congruent with the library hypothesis postulated by fry and salser , which suggested that major sat - dnas found in a group of extant species with any degree of phylogenetic relationship were already present in a common ancestor .\nthese dna sequences formed a pool of sat - dna sequences at low copy number , as a primordial sat - dna library .\nthis idea is depicted for the stallion and donkey y - chromosome in the diagram shown in figure 1b . in the case of the y chromosome in stallion and donkey ( sub - chromosomal regions h - cr or d - cr ) ,\nhowever , in the case of h - pr and d - pr , these species - specific sat - dna profiles can be obtained by a change in the copy number of sat - dnas , without major variation in their sequence or obvious quantitative change .\nalternatively , as in the majority of cases , the same situation can occur as a consequence of simultaneous change in both parameters .\nfor instance , w - cgh performed using two closely related grasshoppers , produces results on some autosomes similar to those reported here for the y chromosome .\nthe results obtained in grasshoppers were identical irrespective of the species employed as the chromosomal strip for probe landing .\nthis fact suggested that , in addition to heterochromatic compartmentalization on constitutive heterochromatin , variation in sat - dna family copy number , rather than sequence divergence , may account for the differential presence of dna families in the species compared .\nin addition to the genome macro - variations concerning chromosome number and morphology described for horse and donkey , it is interesting to stress that eight centromere repositioning episodes occurred when the karyotypes of zebra , horse and stallion were compared .\nthis phenomenon presupposes the inactivation of old centromeric regions , accompanied by the rapid loss of centromeric satellite dna and by the dispersal of pericentromeric duplications over a relatively wide area of the chromosome .\nthis scheme of genome re - patterning is congruent with our observations regarding sat - dna expansion and contraction in the y , as well as other autosomes and the w - cgh , and could probably be used as a quick test to study this phenomenon .\nfinally , the differences in sat - dna found in some autosomes must be taken into account in explaining the sterility observed when hybrids are produced .\nhorse - donkey hybrids ( mules and hinnies ) exhibit massive meiotic dysfunction at the primary spermatocyte stage , and a large part of this dysfunction is caused by the incompatibility of synaptonemal pairing between paternal and maternal chromosomes , resulting in the total arrest of spermatogenesis .\nthis aspect is of interest , as it is known that differences in heterochromatin content in pericentromeric or distal chromosome regions , even within the same species , cause chiasma redistribution due to misleading chromosome pairing .", "answer": "the genome of stallion ( spanish breed ) and donkey ( spanish endemic zamorano - leons ) were compared using whole comparative genomic in situ hybridization ( w - cgh ) technique , with special reference to the variability observed in the y chromosome . \n results show that these diverging genomes still share some highly repetitive dna families localized in pericentromeric regions and , in the particular case of the y chromosome , a sub - family of highly repeated dna sequences , greatly expanded in the donkey genome , accounts for a large part of the chromatin in the stallion y chromosome .", "id": 954} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 59-year - old man presented with a swelling of the left lower extremity that had begun two months earlier .\nfor further evaluation , we performed computed tomography ( ct ) venography and pelvic magnetic resonance imaging ( mri ) .\nthe ct venography axial images showed a 2.3 cm cystic mass compressing the left common femoral vein ( fig .\nthe mri images showed a cystic mass compressing the left common femoral vein as well ( fig .\nwe suspected adventitial cystic disease ( acd ) of the common femoral vein , and the patient underwent an operation . under general anesthesia in a supine position , the femoral artery and vein were dissected for about 5 cm with a longitudinal incision on the left inguinal area .\nsurgical exploration showed an approximately 2.0 cm sized cystic mass that originated from the adventitia of the common femoral artery and was compressing the common femoral vein .\nthe cyst that had adhered to the femoral artery was removed first , and the part of the wall that was attached to the cyst in the femoral artery was partially resected .\nangioplasty was performed to repair the femoral artery whose wall was partially resected . because the patient had had a partial circulation problem in the vein before the surgery and thus venous obstruction was possible , a polytetrafluoroethylene ( ptfe ) patch was used for angioplasty instead of using an autologous vein graft . a cystic mass excision with ptfe roofing angioplasty\nmicroscopically , the presence of a mucinous cyst and vessel wall degeneration confirmed cystic adventitial disease of the common femoral artery ( fig .\nacd is an unusual cystic tumor of the blood vessels characterized by the accumulation of a mucinous substance in the adventitia .\nacd is an uncommon disease that was first described in 1947 by atkins and key .\nacd accounts for only 0.1% of cases of vascular disease , and among them , 85% of all cases of acd occur in the popliteal arteries , while fewer cases appear in the femoral arteries .\nthe first case of common femoral artery acd was reported by jaquet and meyer - burgdorff in 1960 .\nit was reported that the prevalence is 5 times higher in males than in females .\nthe age of occurrence ranges from 11 to 72 years , and the average age is 42 .\nfour theories have been proposed about the nature of acd : 1 ) the theory that it is a systemic disorder of the connective tissue ; 2 ) the theory that it is a chronic degenerative change due to repetitive trauma ; 3 ) the developmental theory , which maintains that a joint - related ganglion - like structure is incorporated into the vessels during embryologic development ; and 4 ) the ganglion theory that arterial adventitial cysts originate from joint capsular synovial structures .\nthus continuous trauma from using fishing tools in contact with the thighs was suspected to have contributed to the lesion .\non the other hand , considering that the lesion occurred unilaterally and did not appear on the opposite thigh , repetitive trauma is not an obvious explanation for the lesion .\nthe symptoms of acd can include unilateral claudication of the lower extremity , and in rare cases it shows ischemic neuropathy such as paresthesia , pain , and rhigosis .\nother possible symptoms include arterial obstruction that results in the pulse in the femoral , the popliteal , and the dorsal pedis arteries being weak or not palpable . however , the main symptom in our case was the uncommon occurrence of swelling that appeared due to the venous obstruction .\nin addition , the pulse of the blood vessels of the lower extremities was fully palpable .\nrecently , it has been accepted that angiography using 3-dimensional ct alone is now considered sufficient for diagnosis .\nct angiography is considered to be an important test because it not only determines the site and extent of stenosis but is also useful in evaluating the entire circulation system .\naspiration of the cyst under ct or ultrasonography is a minimally invasive method , but it is difficult to perform and the cyst has a high recurrence rate .\nthis method also has a higher recurrence rate than complete resection involving the vessel with artificial material interposition .\ninterposition provides better long - term patency than the other methods . in this case , in the pre - surgical assessment the lesion was misdiagnosed as originating from the femoral vein instead of from the femoral artery .\nin addition , recurrence will be minimized by our having performed the arterial repair and interposition as well as the cystic mass excision .\nthus we report here a case of acd , a rare disease , with unusual symptoms , that was successfully treated with surgery .", "answer": "arterial adventitial cystic disease is an uncommon type of non - atherosclerotic peripheral vessel disease . \n most cases of arterial adventitial cystic disease occur in the popliteal arteries ; however , fewer cases have been reported in the femoral arteries . \n a 59-year - old male patient visited the hospital with a complaint of a swelling on the lower extremity that had begun two months earlier . suspecting deep vein thrombosis based on a physical examination and ultrasonography from another hospital , tests were performed . magnetic resonance imaging ( mri ) \n was performed for exact diagnosis because venous adventitial cystic disease was suspected by computed tomography venography . \n the mri indicated venous adventitial cystic disease as well . \n thus , a cystic mass excision was performed . in the end , a cystic mass compressing the common femoral vein that originated from the common femoral artery was diagnosed based on the macroscopic findings . \n this case is reported because blood circulation in the vein was impeded due to arterial adventitial cystic disease , and the symptoms improved after the cystic mass excision and polytetrafluoroethylene roofing angioplasty .", "id": 955} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ndesmoid tumors ( dts ) , also called aggressive fibromatosis , are very rare with an estimated incidence of 25 cases per million of inhabitants in european countries [ 1 , 2 ] .\ndts lack the capacity to metastasize but may behave in a locally aggressive fashion and possess a high risk of local recurrence despite adequate surgical resection with negative margins [ 1 , 3 ] .\ndts can develop in any musculoaponeurotic structure and they may be located at virtually any anatomical site .\nthe principal sites of involvement for extra - abdominal fibromatosis are the shoulder , chest wall and back , thigh and head and neck region .\nintra - abdominal fibromatosis arises in the mesentery or pelvis while abdominal tumors arise from musculoaponeurotic structures of the abdominal wall , especially the rectus and internal oblique muscles and their fascial coverings [ 4 , 5 ] . in the surgically treated patients who experience\nrecurrence of dt ( local recurrence rates are about 2565% ) a wide excision is needed in some cases .\nsynthetic meshes often used in extensive abdominal wall reconstruction may present with complications , including infection , bowel adhesion , extrusion , and fistula according to the prosthetic material used .\na prosthetic material with more favorable properties than traditional mesh could have a major effect on surgical practice and patient outcomes , avoiding chronic inflammation and resisting infection after implantation .\nconsidering baumann 's description of the ideal biomaterial for abdominal wall repair , our choice was directed towards a not cross - linked acellular dermal matrix ( adm ) which remodels into host tissue .\nthe matrix serves as a scaffold and becomes rapidly revascularized and infiltrated with host cells , avoiding fibrotic reaction and encapsulation as well as seroma formation .\nthe revascularization of biological matrices is thought to promote access of host immune cells as well , thereby providing further resistance to future infections .\nthis is the first report about the use of the not cross - linked dermal matrix egis in a case of abdominal wall recostruction after extensive dt resection .\nin 2008 , a 37-year - old woman underwent , in a different hospital , exeresis of a neoformation in the epigastric region of the abdominal wall and reinforcement with small prosthetic mesh .\nshe reported an appendectomy , two pregnancies with cesarean births and a voluntary interruption of pregnancy . in 2014 , a recurrence occurred in the context of the rectus abdominis in the left iliac fossa .\nthe patient therefore underwent tamoxifen therapy for 1 year followed by 3 months of neoadiuvant chemotherapy for progressive disease . in september 2015 , magnetic resonance imaging ( mri )\n1a , c , e ) , which revealed a marked progression of the disease ( calculated size 18 10 6.4 cm ) .\nafter discussions at our multidisciplinary sarcoma meeting , the group decision was to treat the patient surgically .\none month later , the woman had a surgical resection through a suprapubic transverse incision .\nthe abdominal flap was cranially detached ; the neoformation invaded completely the left abdominal rectus muscle and partially oblique muscles with an extension of approximately 30 20 cm ( fig .\n1a , 2a ) . the rectus muscle and a large portion of the oblique and transverse muscles were removed en bloc with 1 cm of healthy margin from the mass ( fig .\nintraperitoneal drainage was placed , and a wide continuous solution was adopted in the left abdomen .\nthe not cross - linked porcine dermal matrix egis ( decomed , venice , italy ) 30 20 cm , 1.5 mm thick , was hydrated for 10 min in sterile saline solution and then secured with interrupted absorbable suture ( vicryl 2/0 ) to the fascia and abdominal wall muscles ( fig .\nwe performed caudal mobilization of the abdominal flap and then dermolipectomy of the superfluous integument .\nthe postoperative course was uneventful and the patient was discharged on the 8th postoperative day .\nthere was no evidence of recurrence of the tumor or incisional hernia at 12 months of follow - up ( fig .\n1b , d , f ) and the membrane turned out to be completly incorporated with the sourrounding tissues .\nhistological examination of the resected specimen ( 17 10 6 cm ) revealed tumor - free margins and a whitish lesion with increased thickness and fibrous appearance , which had almost completely invaded the abdominal muscle .\nthe diagnosis was confirmed by the presence of spindle - cellular tumors which had immigrated through muscle tissues as shown by nuclear -catenin staining .\ndfs are neoplasms with infiltrating growth and with a tendency toward local recurrences ; nevertheless , they lack metastatic potential .\nalthough the morphologies of these tumors have been well characterized , their nature and pathogenesis have remained obscure for many years [ 6 , 9 ] . according to the literature\n, the median age at the diagnosis of dfs is about 35 years , and the majority of patients are women . in particular , patients between puberty and the fourth decade of life tend to be female , and in these patients the abdominal wall is the preferred site of involvement . supposed risk factors of desmoids are previous surgical interventions , pregnancy , and hormonal treatment with estrogens . because the tumor biology is notoriously unpredictable , periods of rapid tumor growth can be followed by stability or even regression .\nthe treatment with tamoxifen , as well as chemotherapy and radiation , is controversial , since the long - term clinical improvement is minimal , while surgical excision should be performed only when absolutely necessary .\nabdominal wall integrity after full - thickness surgery can be restored with direct suture , but the occurrence of postoperative incisional hernia is highly reported .\nfor this reason one - stage reconstruction with prosthetic abdominal wall reinforcement increases the chance of definitive cure , enhancing the patient 's perceived quality of treatment .\nrandomized controlled trial observed a double rate of hernia recurrence in the primary suture group compared with the mesh reinforcement group .\nthe meshes used are classified according to their gap size which defines the porosity of the mesh and consequently the behavior with surrounding tissue , but a common tendency to develop postoperative complications was reported with all these devices .\nsynthetic meshes are usually associated with an increased risk of extrusion , adhesion , and following obstruction and enterocutaneus fistula formation , especially when placed in an overlay fashion .\nmoreover , patients who have had radiation to the abdominal wall prior to reconstruction are at increased risk for wound healing complications and subsequent mesh exposure . for that reason , butler et al . recommend avoiding synthetic meshes in patients with radiated abdominal walls .\nthe advent of biological matrices has added a valuable option to the field of abdominal wall reconstruction .\nthe inherent ability of biological matrix to turn into patient self - tissue , and therefore resist infection , allows to implant it in direct contact with the bowel , resulting in fewer adhesions than prosthetic mesh [ 8 , 12 ] .\nthese bioprosthetic devices , deriving from human or animal dermis , are chemically and enzymatically cleaned to remove all cellular components while maintaining the extracellular matrix , which can be cross - linked or not .\nit is hypothesized that cross - linking treatment adds strength to the matrix , theoretically resulting in lower rates of hernia recurrence as compared to non - cross - linked products .\nin contrast butler et al . in a comparative study had not appreciated any mechanical differences between cross - linked and non - cross - linked matrices .\nmoreover cross - linked matrices revealed delayed revascularization and higher percentage of adhesions resulting in poor integration regarding non - cross - linked adms . despite the great advantages reported about the biological matrices , the high price that distinguishes them , ranging from usd 8.60/cm to usd 22.00/cm , remains a high deterrent to their use .\none variation of the biological materials , egis , has not been described yet in the literature for abdominal wall reconstruction after tumor excision .\negis ( decomed , venice , italy ) is a dry porcine adm , non - cross - linked , without any chemical preservative ; its very competitive price , about half of the aforementioned costs , allows us to choose the benefits of a biological matrix with the advantage of controlled expense .\nwe report for the first time the successful use of egis in a complex abdominal wall reconstruction following the resection of a large dt .\nthe matrix was well accepted without any postoperative complications and no evidence of recurrence of the tumor or incisional hernia has been reported 12 months later . in conclusion\n, this single - case experience makes us to consider the biological matrix egis , as well as other adms , an ideal alternative to synthetic mesh , mainly in cases with a potential risk of infection .\nthe protocol for data collection of this case has been approved by the institute 's committee and complies with the helsinki guidelines for human studies .", "answer": "desmoid tumor is a rare monoclonal fibroblast proliferation that is regarded as benign . \n the clinical management of desmoid tumors is very complex and requires a multidisciplinary approach because of the unpredictable disease course . for those cases localized in the anterior abdominal wall , symptomatic and unresponsive to medical treatment , radical resection and reconstruction with a prosthetic device \n are indicated . \n we present here a case of desmoid fibromatosis of the left anterolateral abdominal wall with a marked increase of the mass that required a large excision followed by reconstruction with biological matrix . \n the fact that it can be incorporated in patient tissue without a fibrotic response and that it can resist future infections , together with a very competetive price , made the new collagen matrix egis our first choice .", "id": 956} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmorphine and codeine are naturally occurring alkaloids in opioid plants , have long been used as a drug , and are also abused . while the presence of illicit drugs or their metabolites in urine is an evidence of intake , their concentrations in blood are expected to correlate with their effects on the central nervous system .\ncodeine is a potent -opioid receptor agonist which is used for the treatment of adult cough .\nsimultaneously , there have been athletes in sports competitions who use a larger dose in order to improve performance .\nthis practice is contrary to the principle of fair competition and also harmful to the health of the athletes ' body .\nheroin as one of the most widely abused drug , rapidly metabolized to 6-monoacetylmorphine ( 6-mam ) once inside the human body .\nthis specific heroin metabolite 6-mam is detected at a higher concentration usually within 2 to 4 hours , and after six hours , has not been detected in the urine .\nthe absence of 6-mam in urine , however , morphine is both a well - known pharmaceutical agent and an important metabolite of codeine and heroin which have relatively long a detection time .\nmorphine and codeine analysis of urine is used in forensic toxicology to study drug addiction .\nthere are numerous papers published about the simultaneous determination of morphine and codeine in human fluids , including the micellar electrokinetic chromatography ( mekc ) method , disposable pipette extraction ( dpx ) method , high performance liquid chromatography method , liquid chromatography - mass spectrometry , and liquid chromatography / triple quadrupole tandem mass spectrometry ( lc / ms / ms ) method [ 68 ] .\nseveral gas chromatography - mass spectrometry ( gc - ms ) methods have been developed for the analysis of codeine , morphine , or other opiates .\nmuch attention has been directed to the confirmation of morphine and codeine in urine by gc - ms .\na few methods have been developed specifically for the analysis of 6-acetylmorphine ( 6-am ) with morphine and codeine because all three drugs are often present after heroin use .\nassays of morphine and codeine by gc - ms are capable of high sensitivity , specificity , and selectivity .\ngc - ms is superior to other analytical methods which provide important diagnostic value to study the drug abuse .\nthe aim of this study was to establish methods and seek out more reliable identification and quantitation of morphine and codeine for detection addicts sample .\nalthough through in saliva is another approach ; the reliability of saliva analysis is limited by the fact that analyte levels , and even the availability of required sample volume , are again dependent on several physiological factors , nutrition and fluid intake , while the biological effects of the consumed illicit substance may also be a significant factor .\nthe identification of chronic consumers or the late verification of a single intake is feasible using hair as a matrix , but it is not suitable for the early verification of consumption .\nurine is a preferable matrix for analytical purposes in comparison with saliva because of the minimal discomfort caused to sampled individuals , so it is widely available .\nthe simple and effective ethyl acetate extraction was employed in our work , and ethyl acetate was adopted because of its high extraction efficiency .\npropionic anhydride was chosen as the derivatization reagent because it exhibited better effect than acetic anhydride or trifluoroacetic acid anhydride , which could provide preferable stability , and the disadvantage of acetyl derivatives indistinguishable from morphine and the 6-am can be avoided .\n. evaluated propionic anhydride , mbtfa , hfaa , and bstfa for gc - ms analysis of 6-am .\nthey concluded that propionic anhydride gave accurate , precise , and sensitive results while providing compatibility with other methods on the same gc - ms instrument .\nresidual derivatization reagent in the injector will react with drugs in other methods not intended for derivatization .\nthe derivatization procedure accommodates the analysis of opioids commonly requiring gc - ms confirmation in urine .\nconcentrations of the analytes in the samples were expected to be smaller than the low end of the therapeutic range ( 25 ng / ml ) , which highlighted the importance of efforts aimed at increasing the sensitivity of detection .\nthe relative standard deviation of the retention parameters of the target compound was required not to exceed 5% relative standard deviation .\nmorphine [ 10 g / ml in methanol ] and codeine [ 10 g / ml in methanol ] solutions were obtained from the institute of forensic science under the ministry of justice ( shanghai , china ) .\nsodium hydroxide ( purity > 98.0% ) was purchased from sigma - aldrich trading co ( shanghai , p.r . ,\nchina ) , and ethyl acetate ( purity > 98.0% ) was purchased from siyou chemical reagent co. , ltd ( tianjin , china ) , and propionic acid anhydride ( purity > 98.0% ) was purchased from sinopharm chemical reagent co. , ltd ( beijing , china ) .\npyridine was from shenbo chemical co. , ltd ( shanghai , china ) . while methanol was obtained from siyou chemical reagent co. , ltd ( tianjin , china ) .\nultrapure water was prepared by a milli - q purification system from millipore ( bedford , usa ) .\nanalysis was performed on an agilent 6890n gas chromatograph ( gc ) coupled with an agilent 5975b mass spectrometer ( ms , agilent technologies , wilmington , de , usa ) .\nthe capillary column used was a hp-1ms [ 30 m 0.25 mm , 0.25 m ] .\nhelium was the carrier gas at a flow rate of 1.0 ml / min .\nthe temperature program was : initial temperature , 100c for 1.5 min ; ramp at 25c / min to 280c and held for 15 min ; injection temperature , 250c ; and transfer line , 280c .\nelectron impact ionization was performed at 70 ev energy and at a 230c ion source temperature .\nsim mode was applied to quantify analyzes using target ions at m / z 341 , 397 , and 268 for morphine propionyl compound and m / z 229 , 355 , and 282 for codeine propionyl compound ( figure 1 ) .\nthe primary standard stock solutions of morphine ( 100 g / ml ) and codeine ( 100 g / ml ) were separately prepared in 10 ml volumetric flasks with urine ; 10% naoh was added dropwise until ph 9.09.2 was reached , and 1.0 ml of borax buffer solution was added . to this , 3 ml of extraction solvent ( ethyl acetate ) was added and vortex - mixed on a vortexer for 2.0 min , followed by centrifugation at 3000 r / min for 5 min .\nthe supernatant organic layer was transferred into a 5 ml glass test tube and dried under air stream at 60c .\nthe dried residue was reconstituted in 50 l of propionic anhydride and 20 l of pyridine .\nall reagents were vortex - mixed , then heating for 3 min at 80c and dried under air stream at 60c . the dried residue was reconstituted in 50 l of methanol , and 1 l of this solution was injected into gc - ms .\nspecificity was determined by analysis of blank urine , without addition of morphine and codeine to determine possible interference with these compounds . to evaluate the linearity ,\nthe calibration curves were generated using the analyte peak area by linear regression on three consecutive days .\nthe lloq was estimated in the process of calibration curve construction and was defined as the lowest concentration for which precision ( rsd ) was better than 20% .\nqc samples at three concentration levels ( 50 , 200 , and 1600 ng / ml for morphine and codeine ) were analyzed to assess the accuracy and precision of the method .\nagain , the assays were performed on three separate days , and on each day six replicates of the qc samples at each concentration level were analyzed .\nthe assay precision for each qc level was determined as the relative standard deviation ( rsd ) of the measured concentrations .\nthe intra- and interday precisions were required to be below 15% , and the accuracy was required to be within 15% .\nstability in urine was assessed in the autosampler at room temperature for 12 h. the effect of three freeze - thaw cycles was also investigated .\n\n figure 2 shows the typical chromatograms of a blank urine sample spiked with morphine and codeine .\nno interfering endogenous substances were observed at the retention times of the morphine and codeine .\ncalibration curves for morphine and codeine were generated by linear regression of peak area ratios against concentrations , respectively .\nthe regression equation for the calibration plot were y = 2270.9c + 202.3 with r = 0.9974 for morphine , and y = 3099.0c + 31625.7 with r = 0.9958 for codeine ( y is the peak area of analyte , and c is the concentration of analyte in human urine ) , and concentrations are in the range 252000 ng / ml for morphine and codeine , respectively .\nthe lloq for morphine in human urine was 25 ng / ml and the precision and accuracy at lloq were 10.5% and 87.6% , respectively .\nthe lloq for codeine in human urine was 25 ng / ml and the precision and accuracy at lloq were 13.8% and 88.9% , respectively . \nthe precision of the method was determined by calculating rsd for qcs at three concentration levels over three validation days .\nintraday precision was 12% or less and the interday precision was 13% or less at each qc level .\nthe aforementioned results demonstrate that the values are within the acceptable range and the method is accurate and precise .\nthe recovery of morphine and codeine was evaluated by comparing peak area ratios of extracted qc samples with those of reference qc solutions reconstituted in blank urine extracts .\nall the stability studies of morphine and codeine in human urine were conducted at three concentration levels ( 50 , 200 , and 1600 ng / ml for morphine and codeine ) with three replicates for each concentration .\nthe stability results showed that morphine and codeine in human urine were stable during three freeze - thaw cycles .\nstability of morphine and codeine extracts in the sample solvent on autosampler was also observed over a 12 h period .\na stable , selective , and sensitive gc - ms method has been developed for the simultaneous determination of codeine and its metabolite morphine in human urine .\nthis developed method with derivatization for sample preparation was successfully applied for the determination of morphine and codeine in human urine for methodological study .", "answer": "a sensitive and selective gas chromatography - mass spectrometry ( gc - ms ) method was developed and validated for the determination of morphine and codeine in human urine . \n the gc - ms conditions were developed . \n the analysis was carried out on a hp-1ms column ( 30 m 0.25 mm , 0.25 m ) with temperature programming , and helium was used as the carrier gas with a flow rate of 1.0 ml / min . \n selected ion monitoring ( sim ) mode was used to quantify morphine and codeine . \n the derivation solvent , temperature , and time were optimized . \n a mixed solvent of propionic anhydride and pyridine ( 5 : 2 ) was finally used for the derivation at 80c for 3 min . \n linear calibration curves were obtained in the concentration range of 252000.0 ng / ml , with a lower limit of quantification of 25 ng / ml . the intra- and interday precision ( rsd ) values were below 13% , and the accuracy was in the range 87.2108.5% . \n this developed method was successfully used for the determination of morphine and codeine in human urine for forensic identification study .", "id": 957} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe national cooperative dialysis study , the first randomised controlled study of dialysis dose , defined an \nadequacy threshold for end - stage chronic kidney disease patients receiving chronic haemodialysis based on the dialyser clearance of urea , a small solute marker of nitrogen turnover , which was defined in terms of a dimensionless parameter known as the normalised urea clearance , or kt / v ( k , dialyzer urea clearance ; t , dialysis session duration ; and v , urea volume distribution ) . below a sessional threshold kt / v of 0.9 for standard thrice - weekly schedules , complication - free survival was compromised within months .\nsubsequent observational studies suggested that higher doses resulted in improved longer - term outcomes , and by consensus the minimum target kt / v was raised to 1.2 .\na subsequent prospective randomised controlled study , the hemodialysis ( hemo ) study , reported that higher doses did not appear to further improve outcome .\nhowever , subgroup analysis suggested that women may benefit from higher kt / v doses , fuelling suggestions that using standard kt / v targets to prescribe dialysis may lead to under - dosing in women and small men .\nthese studies suggest that , for standard thrice - weekly therapy , medium - term survival ( measured in months ) is dependent on achieving a minimum level of small solute removal , as defined by the national cooperative dialysis study .\njust as the amount of dialysis delivered to patients with end - stage chronic kidney disease is important in determining survival , it was reported that the dose of intermittent haemodialysis or continuous renal replacement therapy ( crrt ) was also important in determining survival in patients with acute kidney injury ( aki ) [ 8 - 10 ] , although this was not a universal finding . as patients with aki continue to have high mortality , and evidence\n- based clinical management is somewhat limited , two prospective multicentre trials were designed to investigate the effect of dose of renal replacement therapy on outcome in patients with aki .\nthe veterans affairs / national institutes of health ( va / nih ) study essentially randomised patients to initially receive either an intensive or less intensive dose of intermittent haemodialysis , or an intensive or less intensive dose of crrt , depending upon severity of illness at the time of randomisation .\n( during the course of the study patients were switched between treatment modalities according to haemodynamic stability . ) during haemofiltration , it is assumed that urea is effectively cleared ( to the extent that the concentration in the effluent ultrafiltrate is equal to that of plasma water ) so that urea clearance can simply be assessed by the total ultrafiltration volume achieved . in this study\n, more intensive renal replacement therapy did not show any survival advantage for either the intermittent haemodialysis or crrt groups .\nhowever , the minimum haemodialysis target kt / v of 1.2 was somewhat higher than that typically prescribed for patients with aki by the recruiting centres .\nin addition , there was no survival advantage for the haemofiltration cohort compared to those treated by dialysis .\nhaemofiltration clears solutes primarily by convection , thus removing a larger spectrum of solutes than haemodialysis , which predominantly clears small water soluble solutes by diffusion .\nthe second study , the renal ( randomised evaluation of normal versus augmented level of renal replacement therapy in icu ) study , assessed the effect of an augmented dose of crrt ( an ultrafiltration rate of 40 ml / kg / h versus 25 ml / kg / h ) . once again\n, this study failed to show any significant effect of dose of convective renal replacement therapy on patient outcomes , although the delivered dosages were less than that prescribed and both small patients ( < 60 kg ) and very heavy patients ( > 120 kg ) were excluded .\nalthough urea can dissociate to cyanate in plasma water and then form carbamylated products in a reversible fashion , with some analogy to glycosylation , it would appear that toxicity from the accumulation of small nitrogenous solutes is not the major determinant of short - term outcome ( days to weeks ) in patients with aki .\naki frequently occurs in the setting of multiple organ failure , and mortality remains high , with patient outcome typically dependent upon the severity of the underlying condition and associated co - morbidities .\nthe replacement of organ function may play a critical short - term role in maintaining life in patients already destined by other factors to have the potential to recover . however , urea clearance is only one component of renal replacement therapies .\nfor example , failure to correct persistent volume overload is associated with not only increased post - surgical morbidity , but also increased risk of aki and mortality .\nthus , for patients with aki , the adequate removal of even smaller moieties than urea is the principal determinant of the adequacy of renal replacement . these moieties are the neglected \nuraemic toxins , including potassium , sodium , hydrogen ions and water ( figure 1 ) .\nthe consequences of the accumulation of these moieties , hyperkalaemia , pulmonary oedema , and acidosis , may be lethal in minutes .\ntoxins play a role over time , and as such may require different clinical management strategies .\nhemo , hemodialysis ; ncds , national cooperative dialysis study ; renal , randomised evaluation of normal versus augmented level of renal replacement therapy in icu ; va / nih , veterans affairs / national institutes of health .\nalthough the delivery of higher doses of haemofiltration or more frequent haemodialysis did not improve overall outcome , higher volume crrt exchange cycles and more frequent haemodialysis treatments will help correct acidosis , and may be appropriate during the initial resuscitation phase of aki .\ncorrection of volume overload may help explain the positive findings and improved clinical outcomes reported from some of the earlier trials of increased dose of renal support , compared to the more recent va / nih and renal studies , which had similar fluid balance targets .", "answer": "traditionally , the dose of haemodialysis or haemofiltration delivered to patients with kidney failure is assessed by urea clearance . for patients with chronic kidney disease below a critical urea clearance threshold , \n patient wellbeing is compromised . \n it was suggested , therefore , that the dose of dialysis or haemofiltration delivered could also affect outcomes for patients with acute kidney injury . \n two major prospective multicentre clinical trials have recently reported that a higher intensity of renal support , by either intermittent haemodialysis or continuous renal replacement therapy , did not improve patient survival or recovery from dialysis . \n it must be recognised , however , that urea clearance is only one component of renal supportive therapy , and other aspects , including volume control , electrolyte homeostasis and acid - base balance , may be equally important targets for patients with acute kidney injury .", "id": 958} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\na 22-year - old - male patient presented with a painless swelling over the left eye along with mechanical ptosis of the upper lid .\nthe mass was located anterior to the orbital rim in the superolateral part of the orbit ; with the posterior edge not palpable as it was within the orbit .\nanterior segment evaluation , intraocular pressure , and fundus examination of both eyes were normal .\na computed tomography showed an iso - to - hypodense mass lesion in the superotemporal aspect of the left orbit , arising possibly from the lacrimal gland since the gland could not be clearly delineated from the mass .\nno obvious changed to the bony orbit could be noted on the scans [ fig .\nfine needle aspiration cytology smears drawn showed no malignant cells ; however , a conclusive diagnosis could not be made .\na working diagnosis of a pleomorphic adenoma of the lacrimal gland was made , and an excision biopsy was performed .\nintraoperatively , the mass was pink , vascular , and well circumscribed but not encapsulated .\nthe lacrimal gland was seen in close relation to the mass , compressed between the mass and the superolateral orbital bony rim .\n( a ) external clinical photograph shows the mass located in the superolateral quadrant of the orbit .\n( b ) axial slice of the computed tomography scan showing the mass in the vicinity of the lacrimal gland ( yellow arrow ) the cut surface was homogeneous and did not have any distended vascular channels , lacrimal tissue , or cystic dilatations . on microscopic examination ,\nspindle cells in compact sheaves closely opposed to thin walled vessels were seen in a fibrocollagenous background [ fig .\nthe nuclei were open , oval , and contained small , uniform nucleoli [ fig .\n. no necrosis was noted , and a few engorged vessels were seen in the outlying area .\nimmunohistochemical studies showed that the tumor cells stained positive for cd 34 and cd 31 , which are markers for endothelium [ fig .\nfurthermore , the tumor stained positive for smooth muscle actin and negative for cd68 [ fig .\nimmunostaining was negative , and the ki-67 proliferation index was low with < 5% of the cells staining positive [ fig .\nthus , the tumor had no conclusive features of a malignancy and the final diagnosis based on its microscopic appearance , and immunohistochemical characteristics was that of a solid variant of angioleiomyoma of the orbit . as it had been excised completely , no further treatment was warranted . at 1-year follow - up , no recurrence was observed .\n( a ) low power view showing spindle cells in a background of fibrocollagenous tissue ( h and e , 10 ) .\n( b ) high power view demonstrating uniform oval nuclei ( h and e , 40 ) ( a and b ) immunohistochemical studies showed that the tumor cells stained positive for cd 34 ( endothelium ) and cd 31 ( 10 ) ( a and b ) immunohistochemical studies positivity for smooth muscle actin and immunonegativity for cd68 ( 10 ) .\n( c ) the ki-67 proliferation index was low with < 5% of the cells staining positive ( 10 )\nthe differentials for such an orbital tumor could be cavernous hemangioma , angiomyofibroma , or complex orbital angiomyoma . the tissue of origin of angioleiomyoma is considered to be smooth muscle ; so the possible native tissues from which the tumor could have arisen include blood vessels , pericytes , mller 's muscle or the capsulopalpebral muscle of hessar .\nangioleiomyoma is well recognized within the spectrum of vascular lesions of the soft tissues and has been subdivided into three types solid , venous , and cavernous .\nsince there were no dilated cavernous spaces within our tumor , we consider our case to be a solid variant .\nmorimoto , who classified angioleiomyomas , observed that solid variants are often painful and seen in the extremities .\nin contrast to his comments , our case was a solid variant which was painless .\ndescribed an angiomyofibroma of the orbit as a hybrid tumor exhibiting characteristics of a vascular leiomyoma and cavernous hemangioma .\nthe lack of the cavernous venous channels , the unusual location , and absence of the classical purplish hue rule out cavernous hemangioma and angiofibroma in our case .\njakobiec has also described in detail the characteristics of a complex orbital angiomyoma , which had features of a lymphangiohemangioma .\nthree of them were located in the muscle cone , two of them were located in the superotemporal orbit , and one was located in the inferior orbit .\ntwo other eyelid angioleiomyomas were also described in the same series . of these eight cases ,\nbased on their histological classification , however , only one case was the same type as our case : the solid variant ; five cases were of the cavernous type and two cases were venous type .\nalam et al . , have also reported a similar tumor from the anterior orbit , which was found to be of the cavernous subtype .\npreoperative magnetic resonance imaging may provide some clues : magnetic resonance findings of peripheral angioleiomyomas were relatively nonspecific , but t2-weighted images show a mass with mixed areas that are both hyper- and iso - intense relative to the skeletal muscle and a hypointense rim .\nangioleiomyomas of the orbit are rare tumors with good prognosis , and the treatment of choice remains complete surgical excision .", "answer": "we describe the clinicopathological features of a solid variant of orbital angioleiomyoma . \n a review of clinical records , diagnostic , and radiographic studies combined with histopathological evaluation with standard histochemical staining and immunohistochemistry was conducted . a 22-year - old male patient presented with a mass in the region of the left lacrimal gland that was gradually increasing over the past 2 years . \n radiological and clinical examinations showed no signs suspicious of a malignancy and fine needle aspiration cytology was inconclusive . therefore \n , an excision biopsy was performed . \n on histopathological examination , the picture was consistent with a benign spindle cell tumor . immunohistochemistry showed positivity for cd 34 and cd 31 ( markers for vascular endothelium ) . \n the tumor also showed positivity for smooth muscle actin and ki-67 proliferative index was low . \n angioleiomyomas are rarely encountered in the orbit and has features seen in leiomyoma as well as some vascular tumor elements . in most cases , surgical excision is usually curative .", "id": 959} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nto study the short - term effects of waterborne depleted uranium ( du ) , atlantic salmon parr ( n = 6 ) were exposed for 48 h to 0 , 0.25 , 0.5 and 1.0 mg / l uranyl acetate ( uo2(ch3coo)22h2o , purity 98.0% , specific activity 1.459 10 bq / g , fluka , sigma - aldrich , buchs , switzerland ) dissolved in lake water collected from lake maridalsvannet , oslo , norway .\nfish experiments were approved by the norwegian animal research authority ( nara i d : 3026 ) and conducted at the figaro facility for environmental radioactivity studies ( norwegian university of life sciences , s , norway ) .\nall operations strictly followed the norwegian welfare act and research animal legislation . immediately after the exposure\nsamples were then stored in ultrafreezer ( 80 c ) until further analysis . for rna isolation ,\nthe rneasy plus mini kit ( qiagen , hilden , germany ) was used to extract total rna from 20 to 30 mg frozen liver .\nthe procedures have been previously described in detail , . the rna yield and purity ( yield > 200 ng/l , 260/230 > 2.0 , 260/280 > 1.8 ) were determined using nanodrop spectrophotometer ( nd-1000 , nanodrop technologies , wilminton , delaware , usa ) .\nthe rna integrity ( rin > 9.0 ) was determined using bioanalyzer rna 6000 nano chips ( agilent technologies , santa clara , california , usa ) following the manufacturer 's manual .\nthe microarray probes ( totally 55,418 features ) were designed using the consensus sequences of two salmonid fish , salmo salar and oncorhynchus mykiss from the cgrasp 44 k salmonid oligoarray ( 35,920 sequences ) , release 11/09 complimented by ncbi unigenes ( 2995 sequences from s. salar , build 31 and 16503 sequences from o. mykiss , build 27 ) .\nthe cross - hybridization potential of the array probes was predicted to be less than 7% ( 3587 probes ) .\na high density 60,000-feature ( 60 k ) custom salmonid oligonucleotide array was then manufactured by agilent technologies ( santa clara , ca , usa ) .\nthe custom salmonid array platform is currently available in gene expression omnibus ( geo i d : gpl18864 ) .\nthe agilent one - color microarray - based gene expression analysis ( v6.5 ) protocol ( agilent technologies ) was used in the microarray analysis with small modifications .\ntwo hundred nanogram of liver total rna was used as input material for array experiment ( n = 3 ) .\nthe hybridized array slides were scanned using agilent microarray c scanner ( agilent technologies , scan region : 61 21.6 mm , resolution : 3 m , output tiff image : 20 bit ) .\nthe agilent feature extraction ( fe ) software ( v10.7 ) was used to extract raw data from scanned array images . the quality assessment for extracted data\nwas based on the quality control ( qc ) files generated by the fe software ( table 1 ) and correlations of signal intensity of control probes between different arrays .\nhigh quality raw data ( signal intensity values ) was further processed using genespring software ( v11.0 , agilent technologies ) .\nbriefly , raw data were first corrected for background signals , flagged for low quality and missing features and then normalized within- and between - array using 75% quantile method .\nvalues from replicate features were computed for median and merged to a single normalized signal intensity value for each rna source sequence .\nafter raw data processing , in total 40,267 features were log-2 transformed and used for downstream statistical analysis to determine differentially expressed gene transcripts ( degs ) .\nto study the short - term effects of waterborne depleted uranium ( du ) , atlantic salmon parr ( n = 6 ) were exposed for 48 h to 0 , 0.25 , 0.5 and 1.0 mg / l uranyl acetate ( uo2(ch3coo)22h2o , purity 98.0% , specific activity 1.459 10 bq / g , fluka , sigma - aldrich , buchs , switzerland ) dissolved in lake water collected from lake maridalsvannet , oslo , norway .\nfish experiments were approved by the norwegian animal research authority ( nara i d : 3026 ) and conducted at the figaro facility for environmental radioactivity studies ( norwegian university of life sciences , s , norway ) .\nsamples were then stored in ultrafreezer ( 80 c ) until further analysis . for rna isolation ,\nthe rneasy plus mini kit ( qiagen , hilden , germany ) was used to extract total rna from 20 to 30 mg frozen liver .\nthe procedures have been previously described in detail , . the rna yield and purity ( yield > 200 ng/l , 260/230 > 2.0 , 260/280 > 1.8 ) were determined using nanodrop spectrophotometer ( nd-1000 , nanodrop technologies , wilminton , delaware , usa ) .\nthe rna integrity ( rin > 9.0 ) was determined using bioanalyzer rna 6000 nano chips ( agilent technologies , santa clara , california , usa ) following the manufacturer 's manual .\nthe microarray probes ( totally 55,418 features ) were designed using the consensus sequences of two salmonid fish , salmo salar and oncorhynchus mykiss from the cgrasp 44 k salmonid oligoarray ( 35,920 sequences ) , release 11/09 complimented by ncbi unigenes ( 2995 sequences from s. salar , build 31 and 16503 sequences from o. mykiss , build 27 ) .\nthe cross - hybridization potential of the array probes was predicted to be less than 7% ( 3587 probes )\n. a high density 60,000-feature ( 60 k ) custom salmonid oligonucleotide array was then manufactured by agilent technologies ( santa clara , ca , usa ) .\nthe custom salmonid array platform is currently available in gene expression omnibus ( geo i d : gpl18864 ) .\nthe agilent one - color microarray - based gene expression analysis ( v6.5 ) protocol ( agilent technologies ) was used in the microarray analysis with small modifications .\ntwo hundred nanogram of liver total rna was used as input material for array experiment ( n = 3 ) .\nthe hybridized array slides were scanned using agilent microarray c scanner ( agilent technologies , scan region : 61 21.6 mm , resolution : 3 m , output tiff image : 20 bit ) .\nthe agilent feature extraction ( fe ) software ( v10.7 ) was used to extract raw data from scanned array images . the quality assessment for extracted data\nwas based on the quality control ( qc ) files generated by the fe software ( table 1 ) and correlations of signal intensity of control probes between different arrays .\nhigh quality raw data ( signal intensity values ) was further processed using genespring software ( v11.0 , agilent technologies ) .\nbriefly , raw data were first corrected for background signals , flagged for low quality and missing features and then normalized within- and between - array using 75% quantile method .\nvalues from replicate features were computed for median and merged to a single normalized signal intensity value for each rna source sequence .\nafter raw data processing , in total 40,267 features were log-2 transformed and used for downstream statistical analysis to determine differentially expressed gene transcripts ( degs ) .\nthis article describes high quality transcriptomic datasets generated from an ecotoxicological study on the early stress responses in atlantic salmon after short - term ( 48 h ) exposure to waterborne depleted uranium ( du ) using a custom microarray for salmonid fish .\nthe full study has recently been published and these datasets may serve as a platform to understand the toxic mechanisms and ecological hazard of environmental radionuclides such as du in fish .", "answer": "potential environmental hazards of radionuclides are often studied at the individual level . \n sufficient toxicogenomics data at the molecular / cellular level for understanding the effects and modes of toxic action ( moas ) of radionuclide is still lacking . \n the current article introduces transcriptomic data generated from a recent ecotoxicological study , with the aims to characterize the moas of a metallic radionuclide , deplete uranium ( du ) in an ecologically and commercially important fish species , atlantic salmon ( salmo salar ) . \n salmon were exposed to three concentrations ( 0.25 , 0.5 and 1.0 mg / l ) of du for 48 h. short - term global transcriptional responses were studied using agilent custom - designed high density 60,000-feature ( 60 k ) salmonid oligonucleotide microarrays ( oligoarray ) . \n the microarray datasets deposited at gene expression omnibus ( geo i d : gse58824 ) were associated with a recently published study by song et al . \n ( 2014 ) in bmc genomics . \n the authors describe the experimental data herein to build a platform for better understanding the toxic mechanisms and ecological hazard of radionuclides such as du in fish .", "id": 960} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nin modern society , the fashion of wearing tight clothes for stylish dressed states or \n comeliness is getting very popular1 . \n\nhowever , specialists reported that excessively pressing certain areas of the human body \n could cause many problems in the cardiovascular systems and visceral organs1 .\nin addition to this pressure inflicted on \n the human body may deform muscles , the skeletal system , and even the overall body type2 , 3 . \n\njeans that are too tight compress a nerve that cuts off sensation to the thighs , and this is \n consistent with human anatomy and physiology4 .\ntrousers that are too tight can squeeze a sensory nerve under the \n hip bone , causing a tingling , burning sensation called paresthesia1 , 4 , 5 . with this as the background , the present study aimed to understand \n the hazards of the habit of wearing tightly fitting clothes in relation to deformations of \n the musculoskeletal system and the movement of the lumbar spine and pelvis for the purpose \n of providing basic data regarding proper habits in wearing clothes for the prevention of \n pain in the musculoskeletal systems2 , 3 .\nso the present study evaluated the effect \n of wearing tight pants on the trunk flexion and pelvic tilting angles in stand - to - sit \n movement and in a seated posture .\nthis study was performed on nine males aged 2027 years ( 23.22.0 years , meansd ) whose \n height and weight were 175.13.2 cm and 62.13.4 kg , respectively .\nsubjects with conditions \n that might affect trunk mobility , such as injury or neurologic deficits of the hip and lower \n extremities during the past year , were excluded from study . the study purpose and methods \n were explained to all the subjects , who provided informed consent according to the \n principles of the declaration of helsinki before participating .\ndata were collected at a sampling rate of 100 hz with a motion capture system \n ( vicon mx , oxford metrics , oxford , uk ) that consisted of eight infrared cameras .\nsixteen reflective markers were \n attached to the lower body according to the plug - in - gait marker set ( oxford metrics ) using \n double - sided tape .\nthe software used for kinematic data collection was nexus 1.4.1 ( oxford \n metrics ) , and the data were analyzed with the polygon 3.1 software ( oxford metrics ) .\nthe \n experimental protocol required the completion of two stand - to - sit trials for each of the two \n pants conditions .\nthe worn pants were made from the same material , cotton , woven into a \n rugged cotton textile .\nwe used general and tight pants from the same company ( g company ) . \n\nthe pants were worn under two conditions in this study : ( 1 ) general pants , worn with sizes \n equivalent to 105110% of the subjects hip , thigh , and calf circumferences , and ( 2 ) tight \n pants , worn with sizes equivalent to 9095% of the subjects hip , thigh , and calf \n circumferences .\neach subject was asked to stand up at a \n self - selected speed from a seated posture and to stand in an erect spine posture . for time \n normalization , the time required for a complete stand - to - sit movement cycle ,\nthat is , from \n movement onset to completion , was considered to be 100% ; values were determined for each 2% \n of the movement , beginning at 0% .\nthe changes in trunk flexion and pelvic posterior tilting \n angles were calculated based on the difference between the maximal and initial angles . as \n the analysis was performed with a withwn - subject design ,\nthe paired t - test was conducted to \n test for differences in pelvic and trunk kinematics values during the maneuver .\nall \n significance levels were set at p<0.05 , and spss version 12.0 ( spss , chicago , il , usa ) \n was used for statistical analyses .\nthe change in the posterior pelvic tilting angle ( 9.3 4.1 ) during the stand - to - sit \n movement when wearing the tight pants increased significantly compared with that when \n wearing the general pants ( 7.0 3.3 ) ( p<0.05 ) .\nthe change of the trunk flexion angle \n ( 19.3 5.4 ) during the stand - to - sit movement when wearing the tight pants increased \n significantly compared with that when wearing the general pants ( 12.0 3.8 ) ( p<0.05 ) . \n the change in the posterior pelvic tilting angle ( 13.3 3.2 ) in the seated posture when \n wearing the tight pants increased significantly compared with that when wearing of the \n general pants ( 10.3 2.9 ) ( p<0.05 ) .\nthe change in the trunk flexion angle ( 25.3 6.1 ) \n in the seated posture when wearing the tight pants increased significantly compared with \n that when wearing of the general pants ( 20.1 5.4 ) ( p<0.05 ) .\npark and yoo reported that the tightness of a waist belt might restricts forward movement \n of the center of mass and that pelvic inclination might be increased as a compensatory \n mechanism2 .\nthey showed that the wearing \n a tight belt could interrupt normal lumbo - pelvic coordination , which might contribute to \n muscle imbalance2 .\nelevated abdominal \n pressure has been shown to cause multidirectional stiffness of the spine5 , 6 .\na \n previous study that used a wide belt reported that the intramuscular pressure on the erector \n spinae could influence spinal stiffness separately from muscle7 .\nthe results of the present study showed that the trunk flexion and \n posterior pelvic tilting angles during the stand - to - sit movement when wearing tight pants \n significantly increased when compared with wearing general pants .\nalso , the trunk flexion \n and posterior pelvic tilting angles in the seated posture when wearing tight pants \n significantly increased when compared with those when wearing of general pants .\nthe lumbar \n and hip rhythm and interaction between the lumbar spine and hip are important kinematic \n factors that are used not only in experimental research but also in clinical \n examination8 , 9 . wearing tight jeans induced excessive lumbar flexion during stand \n to sit movement and in the seated posture .\nthe exaggerated lumbar flexion may overstretch \n posterior connective tissues , such as the interspinous ligament , apophyseal joint capsule , \n and thoracolumbar fascia , or increase stress on discs and apophyseal joints5 .\nposterior pelvic tilt decreases lordosis \n via flexion of the lumbar spine , causes posterior movement of the nucleus pulposus , and \n increases the diameter of the intervertebral foramina5 , 8 .\nslump sitting reduces the \n activation of the spinal stabilizing muscles and is associated with increases in loading on \n the intervertebral disc and connective tissue8 , 9 .\ntherefore , wearing tight pants could \n produce musculoskeletal disorders via abnormal movement and posture in the lumbar spine and \n pelvis .\nso the effects of wearing tight pants need to be investigated in further studies to \n reveal their direct relationship to musculoskeletal problems .\nthe effects of tight clothes \n and accessory items on the human body should also be investigated in order to provide basic \n data for proper use .\nfurther studies will become the starting point for studies regarding \n the effects of wearing tight clothes and tight fashion accessories on the musculoskeletal \n system .", "answer": "[ purpose ] the purpose of this study was to evaluate the effect of wearing the tight pants \n on the trunk flexion and pelvic tilting angles in the stand - to - sit movement and a seated \n posture . \n [ subjects ] nine male subjects were recruited . \n [ methods ] the trunk flexion angle \n and pelvic posterior tilting angle were measured using a motion - capture system during the \n stand - to - sit movement and in a seated posture . [ results ] the trunk flexion and the \n posterior pelvic tilting angles during the stand - to - sit movement and in the seated posture \n when wearing tight pants significantly increased compared with those when wearing of \n general pants . \n [ conclusion ] therefore , wearing tight pants could produce musculoskeletal \n disorders via abnormal movement and posture in the lumbar spine and pelvis . \n so the effects \n of wearing tight pants need to be investigated in further studies to reveal their direct \n relationship to musculoskeletal problems .", "id": 961} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe online version of this article ( doi:10.1007/s00227 - 011 - 1643 - 5 ) contains supplementary material , which is available to authorized users .\nwhite sharks , carcharodon carcharias , observed off the coast of california belong to a genetically distinct population unique to the eastern pacific ( jorgensen et al . 2010 ) .\nsubadult and adults travel long distances offshore from california and northern mexico during yearly migrations ( boustany et al . 2002 ; weng et al . 2007 ; domeier and nasby - lucas 2008 ; jorgensen et al .\nthese offshore movements traverse international waters where individuals are susceptible to fishing mortality , yet few data are available from potential offshore fisheries , confounding efforts to determine white shark population status .\ntherefore , fishery - independent methods must be employed to begin to estimate their population size .\nmark - recapture methods have been used to estimate white shark population sizes in south africa ( cliff et al .\n1996 ) , australia ( strong et al . 1996 ) and the northeast pacific ( chapple et al . 2011 ) .\nthese studies are dependent on the assumption that white sharks return to the same location over multiple sampling periods .\nrecent work has illustrated the short - term [ e.g. , < 8 years or 25% of estimated lifespan ( cailliet et al . 1985 ) ] seasonal site fidelity of sharks to coastal aggregation sites .\nwhite sharks tagged off coastal california and guadalupe island , mexico returned to their tagging location following offshore movements ( domeier and nasby - lucas 2008 ; jorgensen et al .\nsimilarly , a combination of a satellite tag and dorsal fin identification described the movement of a shark in south africa to australia and back in 9 months ( bonfil et al . 2005 ) .\nhowever , no studies have tested the long - term [ e.g. , > 14 years or 50% estimated lifespan ( cailliet et al .\nthese mark - recapture frameworks also assume external identification tags or unique markings are conserved and identifiable throughout the study . shedding and\ntherefore , current research on white sharks has focused on the use of distinctive natural markings as individual identifiers ( klimley and anderson 1996 ; strong et al . 1996 ; bonfil et al . 2005 ; domeier and nasby - lucas 2007 ; gubili et al .\none method proposed for individual identification in white sharks at guadalupe island utilizes pigmentation patterns ( domeier and nasby - lucas 2007 ) .\nthough resighting requires only one photograph of the gill flaps , pelvic fin or caudal fin on either side , initial identification requires photographs of all three of these locations on both sides of the animal .\nin addition , the conditions necessary to support this type of identification , superb water visibility and high recreational diving effort , are unique to only guadalupe island .\ncollecting these data is likely to be too labor intensive and impractical in areas outside of guadalupe island with low water visibility ( e.g. , south africa ) and/or limited diving effort ( e.g. , california ) .\nadditionally , pigmentation patterns in several sharks were shown to naturally change in shape and/or size from year to year ( domeier and nasby - lucas 2007 ) .\nalternately , dorsal fins can be photographed from either side and are often observed out of the water , precluding issues with water clarity or the need for divers .\ndorsal fin identification , requiring limited effort , is possible at all white shark aggregation sites globally .\na comparison of matched individuals using genetic markers and dorsal fin photographs showed a high degree of concordance ( 85% ) between the two techniques over short ( 5 year ) time periods ( gubili et al .\nwhite sharks have been shown to exhibit short - term site fidelity and repeatable individual identification through dorsal fin photographs ( klimley and anderson 1996 ; strong et al .\n2009 ) and body pigmentation ( klimley and anderson 1996 ; domeier and nasby - lucas 2007 ) ; however , in order to understand the long - term status of white sharks , mark - recapture studies must be expanded out to longer time series .\ntherefore , it is imperative to determine whether assumptions regarding site fidelity and identification are valid across these longer time periods ( e.g. , > 14 years ) .\nhere , we aimed to determine ( 1 ) the stability of posterior edge dorsal fin morphology as individual identifiers over long time periods and ( 2 ) use this information to illustrate the long - term site fidelity of individual mature and subadult white sharks at coastal aggregation sites .\nthis study began at the south farallon islands in 1987 ( see anderson et al .\n, the study was expanded to include coastal areas near tomales bay , california and beginning in 2005 , a small amount of marine mammal blubber was used as bait to increase encounter rates and duration .\nhigh - resolution photographs and video were taken of each shark when they came near the surface to investigate a seal - shaped decoy .\nwe extracted dorsal fin images from these photographs and , if above water photographs were not available and water clarity permitted , from underwater video .\nestimates of total length ( tl ) were also made when possible as sharks swam alongside a research skiff of known length .\nimages were assessed for quality based on four criteria : angle , size , focus , and contrast .\nimages of insufficient quality were removed ( see online resources 1 for discussion of photograph processing methods ) .\nexperts ( individuals with demonstrated expertise matching dorsal fin photographs ) then matched the remaining accepted fin photographs within and across all years simultaneously . if individuals were identified multiple times over the study period , we compared the earliest and latest photographs to determine long - term stability of dorsal fin morphology . when possible , secondary characteristics ( e.g. , tags , permanent scars , mutilations , etc . ) were used to validate these matches .\n. experts matched 20 randomly chosen photographs from 12 sharks , which had obvious secondary characteristics ( not evident in the fin photographs ) .\nmatching results from each expert were compared to the true matches based on these known secondary characteristics .\nconfirmed males were sighted nearly twice as often as confirmed females ( 1.8:1 ) , though this ratio may be biased because it is easier to confirm the presence of claspers than the absence .\nif the sex could not be confirmed , the animal was labeled unknown . \nfour experts accurately identified individuals and matches 98% of the time with no false positives and only one false negative .\nsimilarly , gubili et al . ( 2009 ) used genetic data to show nearly 85% accuracy in experts matching dorsal fin photographs .\nannually , limited effort and photograph quality resulted in the identification of few sharks before 2006 when effort increased and digital slrs were used . prior to 2006 , over 60% of sharks were resighted ( 29 of 48 ) . in 2006 and 2007 , significantly more new sharks were recorded ( 76 ) , but by 2008 , 35% ( 27 ) of these new sharks had been resighted at least once .\ntwenty - one individuals were repeatedly identified over periods 5 year , ten individuals 10 years , and five individuals 15 years ( fig . 1 ) .\nto illustrate the stability of markers and the empirical evidence of longevity , we describe five individuals resighted over periods 15 years at south farallon islands ( fig . \n1cumulative number of individuals identified repeatedly over time periods ranging from one to twenty - two yearsfig . \n2individuals a tj , b ct , c ft , d bh , and e rf repeatedly identified by dorsal fin morphology over periods > 15 years . the year indicates the date the photograph was takentable 1yearly identification of five white sharks resighted between 1987 and 20081987198819891990199119921993199419951996199719981999200020012002200320042005200620072008bhxxxxx\n xxxxct x x xxx x xxxxxxxx ftx xxxxxxrfxxx xtjxx xxxxxxx depicts when an animal was sighted .\nall individuals were identified in 1993 when effort was increased cumulative number of individuals identified repeatedly over time periods ranging from one to twenty - two years individuals a tj , b ct , c ft , d bh , and e rf repeatedly identified by dorsal fin morphology over periods > 15 years .\nthe year indicates the date the photograph was taken yearly identification of five white sharks resighted between 1987 and 2008 x depicts when an animal was sighted .\nall individuals were identified in 1993 when effort was increased the longest record was shark tj , a 4.5-m - tl male .\ntj was sighted 8 times over 22 years , initially in 1987 and most recently in 2008 ( fig 2a ) .\nshark ct , a 3.5-m - tl male was sighted on 14 occasions over 20 years ( fig . \nft , a 4-m - tl male , was sighted 7 times in 19 years ( fig . \nbh and rf , a 4-m - tl male sighted 9 times ( fig . \nall tl estimates given refer to the size at the most recent sighting of each shark .\nour findings support the use of the trailing edge of the dorsal fin for long - term photo - identification studies at coastal aggregation sites .\nwe photographically identified five white sharks repeatedly over a period of 1622 years . through the use of secondary characteristics and comparisons of first and last photographs of these five sharks\n, we found no evidence of changes in the size , shape , or arrangement of existing notches on these fins .\nwe did , however , identify two sharks that incurred changes to their dorsal fins within the study period .\nthese two sharks , a 4.9-m - tl female photographed each year from 2004 to 2008 ( fig . \n3a ) and a 4.3-m - tl male sighted november 07 , 2008 , and again 11 days later on november 18 ( fig . \n3b ) , were shown to incur damage to their dorsal fins over the periods sighted . though the trailing edge of the dorsal fin was damaged , creating a new notch , identifiable markings above and below this notch remained unchanged and sufficient for identification , illustrating how even relatively major fin trauma may results in the addition of a notch while leaving ample morphologic information for a positive identification .\nit is possible that the entire fin edge could be removed or altered due to major trauma preventing matching to previous sightings , but we saw no indication of this type of trauma during the 22 years of this study , which suggests this would be an extremely rare occurrence.fig . \n3identification of fins after observations of fin damage . a a female shark photographed in 2004 with a complete fin , in 2005 with large lacerations on the fin , and in 2008 with scars from the damage , but all other distinguishing markings intact .\nb a second shark showing new damage over a two - month period in 2008 identification of fins after observations of fin damage . a a female shark photographed in 2004 with a complete fin , in 2005 with large lacerations on the fin , and in 2008 with scars from the damage , but all other distinguishing markings intact .\nb a second shark showing new damage over a two - month period in 2008 dorsal fin identification also supports the long - term ( 15 years ) site fidelity of white sharks at coastal aggregation sites and provides the longest empirical documentation of white shark longevity to date , > 22 years .\nindividual identification illustrated that animals returned to these sites consistently throughout the study period and potentially during their entire adult life span .\neach animal was not necessarily seen every year , but unequal effort across both spatial and temporal scales most likely contributed greatly to such gaps in identification .\nadditionally , the prevalence of short - term resights ( < 5 years ) is also largely attributed to increased effort during the last 3 years of the study ( fig . 1 ) .\nthis methodology , obtaining one photograph of the dorsal fin , requires far less effort than methods to document body pigmentation patterns and does not suffer from large rates of tag shedding or biofouling as traditional tagging methods do .\nmany of the white sharks in this study have been tagged with ( on occasion multiple ) pop - off archival tags , ultrasonic transmitters and/or floy tags , which have the potential to shed within a short time span ( < 1 year ) ( jorgensen et al . 2010 ) , precluding their use in long - term mark - recapture studies .\nin addition , further effort to automate the matching process will make the process more feasible with large datasets , allowing for the universal comparison of animals across different geographic regions regardless of diving effort or water clarity conditions .\ndorsal fin identification offers the foundation for mark - recapture studies to quantify the population size and trends of white sharks . if possible , we suggest all available data be recorded ( e.g. , fin photographs and body pigments )\ntherefore , we propose that dorsal fins , because of their ease in recording , illustrated longevity and potential for universal application , be prioritized as a method to document individual white sharks . this methodology can not only be used to monitor the status of the white shark population in the northeast pacific , but unlike other photo - identification methods , it can be more uniformly applied to archive white sharks worldwide , standardizing documentation of individuals across vast spatial and temporal scales .\nthis article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .", "answer": "mark - recapture techniques can be used to estimate white shark ( carcharodon carcharias ) population abundance . \n these frameworks are based on assumptions that marks are conserved and animals are present at the sampling location over the entire duration of the study . though these assumptions have been validated across short - time scales for white sharks , long - term studies of population trends are dependent on these assumptions being valid across longer periods . \n we use 22 years of photographic data from aggregation sites in central california to support the use of dorsal fin morphology as long - term individual identifiers . \n we identified five individuals over 1622 years , which support the use of dorsal fins as long - time individual identifiers , illustrate strong yearly site fidelity to coastal aggregation sites across extended time periods ( decades ) , and provide the first empirical validation of white shark longevity > 22 years . \n these findings support the use of fin morphology in mark - recapture frameworks for white sharks.electronic supplementary materialthe online version of this article ( doi:10.1007/s00227 - 011 - 1643 - 5 ) contains supplementary material , which is available to authorized users .", "id": 962} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nImpact of local composition on the energetics of E-centres in Si1\u2212xGex alloys\n\nPaper sections:\n\ncorrelation functions of the random substitutional alloys. Their atomistic nature ensures that there is a distribution of distinct local environments that also exist in real random alloys. For the Si 1\u2212x Ge x alloys considered the Si or Ge atoms can be surrounded by various Si n Ge 4\u2212n coordination shells (n ranging from 0 to 4). This forms a distribution of local environments, which in turn influence the formation and energetics of dopant-defect interactions such as the E-centre 29 . The efficacy of the SQS technique to model random alloys has been demonstrated previously in numerous systems including group IV alloys 5,20,28 , oxides 21,30 , and III-V alloys 22,31 .
The E-centre in Si or Ge is a substitutional donor atom (for example P, As, Sb) bound with a nearest neighbor vacancy. The structure and energetics of E-centres in Si or Ge have been extensively investigated using both experimental and theoretical techniques [32][33][34][35][36] . Here as a criterion for the formation of the E-centre we consider the binding energies. A defect pair such as the PV is bound if the energy difference between the pair and the isolated defects (i.e. P and V being at distances long enough that they do not associate) is negative. The more negative the binding enenrgies the more likely it would be for the PV pair to form.
Modelling E-Centres. Figure 1 is a schematic representation of the SQS cells for the Si 1\u2212x Ge x compositions considered. These have been reported in previous work 29 , however, they have not been employed to systematically investigate the defect processes in Si 1\u2212x Ge x alloys. Here to study the binding of the phosphorous substitutional-vacancy defect (PV pairs ot E-centres) we have calculated the energies of all the different nearest neighbour PV combinations in the seven Si 1\u2212x Ge x alloys considered. To limit defect-image errors typically introduced in computational modelling small supercells we have constructed supercells consisting of two SQS cells each (i.e. 64 atomic sites). Therefore, the total number of PV defects considered were 896, whereas more than 1350 DFT calculations were performed to predict the binding energies. The present approach allows the thorough study of defects for a range of compositions and importantly local environment (i.e. Si-rich or Ge-rich). It is an aim of this investigation to derive trends on the impact of composition and environment around the defect on the energetics of E-centres.
Figure 2 considers the effect of the nearest neighbour host atoms to the P substitutional atom. For Si 1\u2212x Ge x cells with up to 62.5% Si content we calculate that there are also positive PV binding energies. This implies that PV pairs in Si 1\u2212x Ge x (x \u2264 0.625) may not form in some areas of the random alloy. This is not the case for Si 1\u2212x Ge x (x > 0.625) were the PV binding ebergy is always negative (refer to Fig. 2). This is not of course implying that it would be equaly likely for the PV to form at any sites in Si 1\u2212x Ge x (x > 0.625). The more negative PV pairs will be more likely to form and more stable against dissociation.
Figure 3 examines the impact of the first nearest neighbour host atoms to the lattice vacancy. The trend observed is that the E-centre will have a more negative binding energy if it forms in the vicinity of Ge atoms, irresppective of the Si 1\u2212x Ge x random alloy composition. The physical basis of this can be traced to the lattice relaxation of the Ge host atoms (which are larger than Si atoms) in the vacant space.
Figure 4 attempts to sum up the impact of nearest neighbours arounf the E-centre. This is to gain an understanding of whether the E-centres in Si 1\u2212x Ge x prefer to form in Si-rich or Ge-rich regions of the alloy. What can be deduced from Fig. 4 is that E-centres form in the vicinity of one or more Ge atoms, irrespective of the alloy composition. For all the alloys considered Ge is strongly represented in the nearest neighbours around the minimum energy PV. The most energetically favourable PV defects and their nearest neighbour atoms are schematically represented (refer to Fig. 5) for every alloy considered here. The present findings are consistent with previous experimental and theoretical work where it was shown that vacancies preferentially form in the vicinity of Ge atoms 5,25,37 .
Figure 6 summarizes the binding energies with respect to alloy composition. The fitted line indicates that binding energies are not linear as a function of alloy composition (i.e. Vegard's law is invalid in this case). The SiGe ) as a function of composition can be described via the following relation: Where \u03b8 is called the bowing parameter and is calculated to be \u22122.0 eV. Although the trend is very similar, this bowing parameter is considerably higher as compared to the one calculated in previous work 5 . This is due to the more substantial SQS cells (32 atom SQS as compared to 16 atom SQS in ref. 5 ) and the more Si 1\u2212x Ge x compositions used here that allow far more E-centre configurations to be considered. The non-linear dependence of the binding enenrgies with respect to composition is consistent with previous work 5 , however, the present study is far more detailed given more compositions were explored, larger SQS cells and more E-centres with richer nearest neighbour environments. What is the nature of this deviation from linearity and is it determined in other defect processes in Si 1\u2212x Ge x alloys? The Ge content dependence of the most strongly bound PV defects is in agreement with previous experimental studies for donor atom (As and Sb) diffusion in Si 1\u2212x Ge x alloys 2,38 . In particular these experimental investigations established that the activation enthalpies of diffusion of As and Sb are not linearly dependent as a function of the Ge content of Si 1\u2212x Ge x alloy. More recently, Kube et al 3,6 . determined the self-diffusion of Si and Ge in Si 1\u2212x Ge x over a wide range of Ge concentration (x=0.0, 0.05, 0.25, 0.45 and 0.70) and temperatures (963 K-1543 K). These investigations 3,6 showed a non-linear dependence of the activation enthalpy of self-diffusion with Ge concentration with a bowing that is consistent with the present study. Thereafter, Saltas et al 11 . analysed the experimental results within the cB\u03a9 thermodynamic model. In this study, Saltas et al 11 . used the thermoelastic properties (bulk modulus, mean atomic volume and thermal expansion coefficient) of Si and Ge to study the composition and temperature dependence of self-diffusion in Si 1\u2212x Ge x . The resulting deviations from Vegard's law were attributed to the diversification of the bulk properties of Si and Ge 11 . This is anticipated to be the reason for the bowing in the binding energies of the PV defects with respect to composition calculated in the present study, however, further thermodynamic analysis will need to be performed in future work.
Apart from relaxation and thermodynamic issues the electronic properties of the defects including charge transfer can impact the properties of Si 1\u2212x Ge x . To consider this we have performed spin polarized DFT calculations. These calculations enabled us to calculate the amount of charges on the P and its nearest neighbor atoms and plot charge densities localized on the P atoms in each configurations. The relaxed configurations of P interacting vacancies in Si 1\u2212x Ge x are shown in Fig. 7. In each configurations, there is a substantial interaction between www.nature.com/scientificreports www.nature.com/scientificreports/ P and Si (or Ge) is observed. This is reflected in the negative Bader charge on P and positive Bader charge on Si (or Ge) (refer to Fig. 8). The amount of charge on P in each configuration is ~\u22123.00. In each configurations, the P forms three-coordination with adjacent Si (or Ge) atoms and they donate ~1.00 e each to P to form stable P 3\u2212 states. This is further evidenced by the charge density around the P atoms in each configurations (refer to Fig. 8). The Si-P bond distance is calculated to be ~2.30 \u00c5 while the Ge-P bond distance is ~2.40 \u00c5. This is due to the larger atomic radius of Ge than that of Si.
summary. In the present study, electronic structure calculations were used to investigate the defect process of the E-centre in Si 1\u2212x Ge x for a range of compositions. It is shown that the binding energies of the E-centres are strongly dependent upon the composition of the alloy, but also on the local environment around the defect. In particular, the more bound E-centres have at least one Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear. It is shown that the more substantial 32 atom SQS can better describe the defect processes in Si 1\u2212x Ge x as compared to 16 atom SQS cells considered previously. The present study is a paradigm of the employment of the SQS method in conjunction with systematic DFT calculations to describe non-linear energetics in random semiconductor alloys. This approach can be extended to other technologically important systems such as random alloys for materials for photovoltaics and solid oxide fuel cells.
Methods. The binding nature of phosphorous with vacancy defects in Si 1\u2212x Ge x was examined by using the plane wave DFT code CASTEP 39,40 . The correlation and the exchange interactions are described using the
", "answer": "the energetics of the defect chemistry and processes in semiconducting alloys is both technologically and theoretically significant. This is because defects in semiconductors are critical to tune their electronic properties. these processes are less well understood in random semiconductor alloys such as silicon germanium as compared to elementary semiconductors (for example silicon). to model the random silicon germanium alloy we have employed density functional theory calculations in conjunction with the special quasirandom structures model for different compositions. Here we show that, the energetics of substitutional phosphorous-vacancy pairs (E-centres) in si 1\u2212x Ge x alloys vary greatly with respect to the local Ge concentration and the composition of the alloy. the most energetically favourable E-centres have a Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear.The substitution of the silicon native oxide with high-k dielectrics has enabled the replacement of silicon (Si) with materials such as germanium (Ge) or silicon germanium (Si 1\u2212x Ge x ), which have better materials properties (e.g. higher mobilities) 1-10 . Si 1\u2212x Ge x is a random alloy in the sense that two atom species can occupy one lattice site. This in turn can lead to Si-rich and Ge-rich regions that can impact the energetics of point defects. This has been previously demonstrated in Si 1\u2212x Ge x alloys where there is a compositional dependence of self-diffusion (refer to 3,6,11 and references therein) but also oxides where local compositional variation impacts diffusion 12,13 . Recently, Saltas et al 11 . studied self-diffusion in Si 1\u2212x Ge x alloys as a function of temperature and Ge concentration within the cB\u03a9 thermodynamic model [14][15][16][17] . In this study considerable deviations from linearity of the activation energies with respect to compositions were observed 11 . This non-linear behaviour was attributed to the diverse behaviour of the bulk properties of Si and Ge and is consistent with the experimental data.The theoretical investigation of random alloys using advanced techniques such as density functional theory (DFT) is not trivial as it requires a very extensive number of calculations in large supercells. To reduce the supercell size and the number of calculations methods such as the special quasirandom structures (SQS) have been previously proposed 18 and implemented in technologically important random alloys (more details are given in what follows) [19][20][21][22][23] . Considering group IV random alloys previous work has investigated the defect processes in Si 1\u2212x Ge x , Sn 1\u2212x Ge x and Si 1\u2212x\u2212y Ge x Sn y alloys [24][25][26][27][28] .The main aim of the present study is to use extended SQS cells in conjunction with systematic DFT calculations to investigate the energetics of substitutional phosphorous-vacancy pairs (E-centres) in Si 1\u2212x Ge x alloys (x = 0.125, 0.25, 0.375, 0.5, 0.625, 0.75, 0.875). Particular emphasis will be placed on the effect of the composition of the alloy as well as the nearest neighbor environment to the defect. Results and Discussionsi 1\u2212x Ge x structure and E-centres. Typical DFT calculations involve the construction of a supercell with periodic boundary conditions and as such they are immediately applicable for perfectly ordered structures. The situation is not straightforward, however, for disordered random alloys. Brute force methods (i.e. construct a very large supercell and randomly inserting the host atoms) is practically unfeasible for DFT as it necessitates very large supercells to reproduce the statistics of random alloys. Conversely, the SQS approach efficiently mimics the statistics of random alloys using small supercells and therefore it is a method that is compatible with DFT particularly when numerous defect calculations are required [18][19][20][21][22][23] . The qualitative difference of the SQS is that they are designed small-unit-cell periodic structures that mimic the most relevant near neighbour pair and multisite", "id": 963} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe ganoderma strains listed in table 1 were obtained from the korean collection for type culture ( ktct , jeongeup , korea ) , the american type culture collection ( atcc , rockville , md , usa ) , the korean agricultural culture collection ( kacc , suwon , korea ) , the mushroom division of the rural development administration ( eumseong , korea ) , the centraalbureau voor schimmelcultures ( cbs , utrecht , netherlands ) , incheon university ( incheon , korea ) , and konkuk university ( seoul , korea ) .\nganoderma species were cultured on potato dextrose broth ( difco , detroit , mi , usa ) and incubated at 30 for 2 wk .\ncultured mycelia , filtered through 2 layers of miracloth ( calbiochem , la jolla , ca , usa ) , were ground in liquid nitrogen , and genomic dna was extracted using the cetyltrimethylammonium bromide method .\npcrs were performed using a premixed polymerase kit ( taq premix ; tnt research , anyang , korea ) in a 20 l reaction mixture containing 1 l of dna .\namplification of the its region was carried out using a thermal cycler ( takara , tokyo , japan ) at the following conditions : 5 min at 94 for initial denaturation , followed by 30 cycles of 30 sec at 94 for denaturation , 30 sec at 56 for primer annealing , and 1 min at 72 for extension , and 10 min at 72 for a final extension .\npcr products were detected by electrophoresis on 1.2% agarose gels in 0.5 tris - acetate ethylenediaminetetraacetic acid buffer .\npcr products were ligated into the pgem - t easy vector ( promega , madison , wi , usa ) according to the manufacturer 's instructions .\nligation products were transformed into the escherichia coli dh5 competent cell ( rbc , taiwan ) by heat shock .\nplasmid dnas were extracted using the dna hybrid - qtm plasmid mini dna isolation kit ( geneall , seoul , korea ) .\nrecombinant clones were identified , and the presence of inserts was confirmed by ecori restriction enzyme digestion and sequencing ( using the sp6 and t7 promoters ; genotech , daejeon , korea ) .\nnucleotide sequences were deposited in the national center for biotechnology information genbank database ( table 1 ) .\nthe sequences of the its rdna were aligned for phylogenetic analysis using the program bioedit ( http://www.mbio.ncsu.edu/bioedit/bioedit.html ) .\nthe phylogenetic trees were constructed by using the mega5 program and the neighbor - joining method .\nconfidence levels for individual branches of the resulting tree were assessed using the bootstrap test in which 1,000 replicate trees were generated from resampled data .\nthe size of basidiospores from the korean cultivated yeongji strains was determined using a fluorescence microscope ( axio observer a1 ; carl zeiss , jena , germany ) and a 5% koh solution as a mounting medium .\nthe size of each spore was calculated , and the mean value was used in the description .\nthe ganoderma strains listed in table 1 were obtained from the korean collection for type culture ( ktct , jeongeup , korea ) , the american type culture collection ( atcc , rockville , md , usa ) , the korean agricultural culture collection ( kacc , suwon , korea ) , the mushroom division of the rural development administration ( eumseong , korea ) , the centraalbureau voor schimmelcultures ( cbs , utrecht , netherlands ) , incheon university ( incheon , korea ) , and konkuk university ( seoul , korea ) .\nganoderma species were cultured on potato dextrose broth ( difco , detroit , mi , usa ) and incubated at 30 for 2 wk .\ncultured mycelia , filtered through 2 layers of miracloth ( calbiochem , la jolla , ca , usa ) , were ground in liquid nitrogen , and genomic dna was extracted using the cetyltrimethylammonium bromide method .\npcrs were performed using a premixed polymerase kit ( taq premix ; tnt research , anyang , korea ) in a 20 l reaction mixture containing 1 l of dna .\namplification of the its region was carried out using a thermal cycler ( takara , tokyo , japan ) at the following conditions : 5 min at 94 for initial denaturation , followed by 30 cycles of 30 sec at 94 for denaturation , 30 sec at 56 for primer annealing , and 1 min at 72 for extension , and 10 min at 72 for a final extension .\npcr products were detected by electrophoresis on 1.2% agarose gels in 0.5 tris - acetate ethylenediaminetetraacetic acid buffer .\npcr products were ligated into the pgem - t easy vector ( promega , madison , wi , usa ) according to the manufacturer 's instructions .\nligation products were transformed into the escherichia coli dh5 competent cell ( rbc , taiwan ) by heat shock .\nplasmid dnas were extracted using the dna hybrid - qtm plasmid mini dna isolation kit ( geneall , seoul , korea ) .\nrecombinant clones were identified , and the presence of inserts was confirmed by ecori restriction enzyme digestion and sequencing ( using the sp6 and t7 promoters ; genotech , daejeon , korea ) .\nnucleotide sequences were deposited in the national center for biotechnology information genbank database ( table 1 ) .\nthe sequences of the its rdna were aligned for phylogenetic analysis using the program bioedit ( http://www.mbio.ncsu.edu/bioedit/bioedit.html ) .\nthe phylogenetic trees were constructed by using the mega5 program and the neighbor - joining method .\nconfidence levels for individual branches of the resulting tree were assessed using the bootstrap test in which 1,000 replicate trees were generated from resampled data .\nthe size of basidiospores from the korean cultivated yeongji strains was determined using a fluorescence microscope ( axio observer a1 ; carl zeiss , jena , germany ) and a 5% koh solution as a mounting medium .\nthe size of each spore was calculated , and the mean value was used in the description .\nthe phylogenetic analysis of ganoderma species in this study was generally consistent with the findings reported by the group from china .\nthe 62 ganoderma strains were divided into 7 groups , a to g ( fig .\nin addition , ganoderma lucidum were largely divided into two groups ( groups a and g ) .\ngroup a included all the korean g. lucidum strains , as well as the g. lucidum strains from bangladesh and japan , and chinese g. sichuanense and g. lingzhi .\ng. meredithae ( usa and unknown sources ) in group b was closely related to g. lucidum in group a as evidenced by a high bootstrap value of 98% .\ng. multipileum ( china and taiwan ) was grouped within group c and g. tropicum ( china and taiwan ) within group d , with 96% and 99% bootstrap support , respectively .\ngroup e includes three strains of g. resinaceum from the czech republic and uk ( two strains ) , and was supported by very high bootstrap values of 99% .\nstrains of g. weberianum ( australia , china , and philippines ) and two other chinese g. sichuanense strains ( cui 7691 and hmas 86597 ; holotype ) were grouped within group f with 99% bootstrap support . groups e and f were closely related with bootstrap values of 96% .\nit is worth noting that other g. lucidum strains from europe ( france , finland , italy , sweden , and uk ) and canada could be clustered into group g with g. tsugae strains from north america ( canada and usa ) , supported by a very high bootstrap value of 99% .\nthe findings of the current study are consistent with those of park et al . who reported that g. lucidum strains from europe and north america could be clustered into one group together with g. tsugae based on both analyses of the its rdna gene and partial -tubulin gene sequences .\ninterestingly , korean g. lucidum strains could be clustered into a group together with g. sichuanense and g. lingzhi strains from china .\nreported that g. lucidum is incorrectly recorded in china , as well as in other countries , and suggested that the name ' g. lucidum ' as used for the chinese species should be corrected as g. sichuanense .\nhowever , they did not obtain sequences from type specimens of g. sichuanense ( the holotype ; hmas 42798 ) .\nreported that korean g. lucidum ( asi-7004 ) could be clustered into one group together with chinese g. lucidum and g. lingzhi based on the its2 sequences and rna secondary structures .\nfurthermore , cao et al . reported that g. sichuanense ( included the holotype ; hmas 42798 ) was distantly phylogenetically related to g. lingzhi ( included the holotype ; wu 1006 - 38 ) , but it was closely related to g. resinaceum . with regard to the morphological characteristics , it has been reported that chinese g. lucidum ( g. lingzhi ) has a yellow pore surface , european g. lucidum has a white pore surface , and korean g. lucidum has pale brownish thread - like tissues in the middle of the context .\ncao et al . found that the morphological characteristics of ' g. lucidum ' from east asia were consistent with those of g. lingzhi .\nthus , they concluded that g. sichuanense was a distinct species since they display obvious morphological differences from g. lingzhi and suggested that the name ' g. lucidum ' should be corrected as g. lingzhi not g. sichuanense .\nit is commonly called \" yeongji \" in korea , \" lingzhi \" in china , and \" reishi \" or \" mannentake \" in japan .\nhowever , the ganoderma species from various countries including africa , oceania , america , asia ( china , korea , and japan ) , and europe have been incorrectly reported as g. lucidum .\nin addition , moncalvo et al . classified g. lucidum collections from different regions ( asia and europe ) into different species based on its and partial nuclear large subunit ribosomal dna sequences .\nthis is similar to the results of our its nucleotide sequence analysis of g. lucidum .\nlikewise , hong and jung reported that the g. lucidum from korea and japan were monophyletic , and were distinguished from the g. lucidum from europe and north america based on sequence analysis of mitochondrial small - subunit ribosomal dna .\nas described above , the taxonomy of g. lucidum has been reported by many researchers .\nnevertheless , the name g. lucidum has been misapplied to various species around the world .\nthe results of this study also reveal that korean g. lucidum was clustered into one group together with chinese g. sichuanense and chinese g. lingzhi ( both formerly g. lucidum ) , and it was clearly separated from g. lucidum from europe and north america .\nin addition , g. sichuanense were divided into two groups ( groups a and f ) .\ng. sichuanense strains ( cui 7691 and hmas 86597 ; holotype ) , including the holotype , could be clustered into group f together with g. weberianum , and it was closely related to g. resinaceum .\ncao et al . also reported that the size of basidiospores of g. lingzhi [ ( 9.85 0.85 ) ( 6.4 0.6 ) m ] differs from that of g. sichuanense [ ( 8.3 0.9 ) ( 5.8 0.8 ) m ] .\ninterestingly , the average size of the basidiospores from the korean cultivated yeongji strains [ ( 10.65 0.65 ) ( 6.6 0.6 ) m for asi-7004 , ( 10 1 ) ( 6.4 0.3 ) m for asi-7071 ] were similar to that of g. lingzhi ( fig .\nthe comparison of the its rdna sequences and the estimation of the basidiospores size presented in this study confirm previous findings and contribute additional evidence that suggests the naming korean cultivated yeongji strains of ' g. lucidum ' should be renamed as g. lingzhi .", "answer": "ganoderma lucidum has a long history of use as a traditional medicine in asian countries . \n however , the taxonomy of ganoderma species remains controversial , since they were initially classified on the basis of their morphological characteristics . \n recently , it was proposed that g. lucidum from china be renamed as g. sichuanense or g. lingzhi . in the present study , \n phylogenetic analysis using the internal transcribed spacer region rdna sequences of the ganoderma species indicated that all strains of the korean ' g. lucidum ' clustered into one group together with g. sichuanense and g. lingzhi from china . \n however , strains from europe and north american , which were regarded as true g. lucidum , were positioned in a clearly different group . in addition , the average size of the basidiospores from the korean cultivated yeongji strains was similar to that of g. lingzhi . based on these results , \n we propose that the korean cultivated yeongji strains of ' g. lucidum ' should be renamed as g. lingzhi .", "id": 964} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthey may be seen in midline or para - axial location , from the brain to the sacral area .\nthey display a particular tendency to locate in the sacrococcygeal and pre - sacral regions . reported incidence of tumors at these sites\nthe oropharyngeal cavity is exceedingly rare for teratomas , 2% of all teratomas , present as large masses protruding from the oropharyngeal area .\nthough oropharyngeal teratomas have a benign histopathology , they are potentially lethal as they may cause airway obstruction and respiratory compromise .\nso , principles of management in such patients comprise of the immediate postpartum establishment of a secure airway , if needed via tracheostomy and complete surgical resection of the mass .\na 1980 g female infant born to 22-year - old mother after 38 weeks gestation presented with a growth in oral cavity associated with respiratory distress .\nthe mother had undergone ultrasonography examination during pregnancy , but the report of the same was unavailable . on examination ,\ncleft palate was present and a palatal tumor of size 4 cm 3 cm was found in the cleft area [ figure 1 ] .\nit was hampering feeding . computed tomography scan showed mass lesion in the palatal region ( attached to the palate , more on the right side ) .\nno intracranial extension [ figure 2 ] . computed tomography scan image after due preparation , the patient was operated , and the mass was excised in toto [ figure 3 ] .\nhistopathologic examination revealed a teratoma composed of mature glial tissue , choroid plexus , glands lined by respiratory type , columnar mucin secreting , and melanin pigment bearing epithelium .\npools of myxoid matrix bearing physaliferous cells are present ( notochord like / chondroid areas ) [ figures 4 and 5 ] .\nmicroscopic picture 1 microscopic picture 2 following excision , patient recovered faster and gained weight .\nnow , the patient is under routine follow - up , and palatoplasty has been done .\nteratomas are the tumors which contain tissues derived from all three germ layers . these contain tissues foreign to the anatomical site of origin .\nmost of the teratomas in the pediatric age group are benign , but reports of malignant teratoma do exist .\nbasic histological classifications which are widely used ( arnold 's system ) are : \n dermoid tumors : these are composed of ectoderm plus mesoderm .\nthis is the most common form of teratomateratoids : these are poorly differentiated tumors and contain all three germ layersteratomas : these also contain tissue from all three germ layers .\nthey are histologically more identifiableepignathus : these are tumors which contain fully developed organs and appendages .\nthe large cervical and nasopharyngeal teratomas which obstruct fetal swallowing of amniotic fluid may contribute to polyhydramnios .\nthis is the most common form of teratoma teratoids : these are poorly differentiated tumors and contain all three germ layers teratomas : these also contain tissue from all three germ layers .\nthey are histologically more identifiable epignathus : these are tumors which contain fully developed organs and appendages . the large cervical and nasopharyngeal teratomas which obstruct fetal swallowing of amniotic fluid may contribute to polyhydramnios .\nother imaging technique such as magnetic resonance imaging , is useful in finding out the anatomical relationship of these tumors .\nclinical differential diagnoses of oropharyngeal teratoma are cystic hygroma , lymphangioma , duplications and neuroblastoma .\nmoreover , the histopathological differential diagnosis includes hamartoma , dermoid cyst , and a heterotopic gastrointestinal cyst . with growth , oral teratomas\nthat is why , the respiratory distress may be less . the neonates with oral teratomas\nthe basic principle of management of oropharyngeal teratomas is the establishment and maintenance of a secure airway .\nif an oropharyngeal teratoma is diagnosed antenatally , elective delivery or lower segment cesarean section is carried out .\nif orotracheal / nasotracheal intubation is failed / or difficult , tracheostomy must be done .\nsurgical goal is to remove the complete mass in toto , as a residual tumor may cause recurrence .\nassociated cleft palate can be repaired when the child grows up , that is , at the age of 1 years . during follow - up , afp should be monitored . in our case , all the afp levels were within normal range .\nearly diagnosis , the establishment of the good airway , complete excision of tumor and timely follow - up should increase the survival of newborns with oral teratomas .", "answer": "for congenital teratomas , oropharyngeal cavity is one of the rarest sites ( 2% of all teratomas ) . \n they are rarely picked up by prenatal ultrasonography . \n postnatally , newborns present with respiratory distress and at this point role of pediatricians is very crucial in establishing secure airway after which they need to be carefully evaluated and surgically managed . \n we present a female neonate with palatal teratoma which was treated successfully with surgery .", "id": 965} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nurea cycle disorders ( ucd ) are among the most common inborn errors of metabolism of the liver .\ncitrullinemia can be classified into three types : neonatal / infantile ( types i and iii ) and the adult form ( type ii ) .\nmore than 20 patients with citrullinemia have undergone liver transplantation , with favorable therapeutic results . however , the number of cases with auxiliary partial orthotopic liver transplantation ( apolt ) is limited .\napolt was initially performed in patients with acute liver failure and non - cirrhotic metabolic liver disease to compensate for enzyme deficiencies without complete removal of the native liver and for small - for - size living donor grafts [ 3 - 5 ] .\nour patient was a 27-year - old man who was diagnosed with adult - onset type ii citrullinemia ( ctln2 ) at age 24 .\nthe patient had been treated with a low protein diet and oral administration of lactulose .\nrecently , the patient has had more frequent alterations of his mental status with irritability and altered consciousness .\neven though oral administration of l - arginine , kanamycin and intravenous hyperalimentation with branched chain amino acids was started , his plasma levels of ammonia and citrulline were highly elevated , up to 844 g / dl ( normal range , 19 to 87 g / dl ) and 682 mol / l ( normal range , 12 to 55 mol / l ) , respectively . despite the conservative medical treatment including alternative pathway medication ,\nintermittent continuous renal replacement therapy and hemodialysis , his condition failed to improve . therefore , living donor liver transplantation was planned using a right lobe graft from his 25-year - old sister .\nhowever , the estimated volume of the donor 's right lobe was 800 ml compared to 180 ml of the left and in addition there was a type iii portal vein anomaly .\nwe eventually decided to perform an apolt using the extended left lobe of the liver from the donor .\nthe actual graft volume was 200 g and the graft - to - recipient weight ratio ( grwr ) was only 0.33% .\nthe patient 's extended left lobe ( including caudate lobe ) was resected and the extended left lobe graft ( including middle and left hepatic vein ) was transplanted orthotopically .\nthe left and middle hepatic vein trunk of the extended left lobe graft was anastomosed to the left and middle hepatic vein trunk of the recipient in end - to - end fashion with interposition venoplasty using the recipient 's greater saphenous vein as a patch . the left portal vein of the graft was anastomosed to that of the recipient in end - to - end fashion . considering that the graft was too small ,\nthe recipient 's right portal vein was narrowed by surgical clipping , instead of total diversion , for prevention of the development of portal venous hypertension .\nthe left hepatic artery of the graft was anastomosed to that of the recipients in end - to - end fashion .\nintraoperative doppler ultrasonography demonstrated that portal and arterial blood flow were well maintained in both the native liver and the graft .\non postoperative day 7 , abdominal computed tomography demonstrated orthotopically transplanted small left lobe graft with well - enhanced pattern ( fig .\nthe post - operative course was uneventful and the patient was discharged without any problems .\nthe plasma concentrations of ammonia were at the upper limits of normal , so only a low protein diet ( 50 g / day ) was supplied without any specific medication . on post - operative day 33 ,\nthe patient reported a sudden severe visual disturbance and the plasma levels of ammonia were noted to have increased up to 209 g / dl .\nthe estimated computed tomography volume of the graft was decreased to 190 ml and a left portal vein stenosis was suspected .\nimmediate coil embolization of 8th segmental branch of right anterior portal vein and self - expandable stent placement for left portal vein was performed in order to increase the portal flow to the graft ( fig .\nstent insertion day 7 , the calculated computed tomography volume of the graft was increased to 250 ml ( fig .\napolt was initially introduced as a temporary or permanent support for patients with fulminant hepatic failure .\napolt can provide an adequate hepatic mass to correct underlying enzyme deficiencies in adult patients with ucd .\nthis procedure can be carried out to overcome the limitations of graft volume in living donor liver transplantation . in korea ,\ntherefore , living donor liver transplantation is the only treatment option for patients with metabolic liver disease such as ucd . in this case , the graft weight of 200 g and the grwr of 0.33% are the smallest graft and lowest margin ever reported to meet the minimum requirements for the demands of adequate metabolic function in adults .\nbecause the remaining native liver function , except for the metabolism of ammonia , is normal , the differential diagnosis including portal steal phenomenon and rejection as well as other problems associated with the vascular system is difficult .\nthus the plasma ammonia level is a valuable follow up marker and should be closely monitored in such patients .\nin addition , careful monitoring of the portal flow to the graft is important for the detection of delayed graft dysfunction .\nselective portal vein embolization is a useful method for the increase of portal flow to the graft . in conclusion\n, apolt can be a life saving procedure and an effective treatment for patients with adult - onset type ii citrullinemia , especially when a deceased donor graft is not available or when candidate donors have insufficient graft volume .\nhowever , further confirmation is needed with additional patients and long - term follow - up .\nhow much volume of graft can be transplanted successfully is questionable in cases of inborn error of metabolism , such as ucd .", "answer": "adult - onset type ii citrullinemia ( ctln2 ) is a disorder caused by an inborn error of metabolism affecting the liver . \n ctln2 is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia due to highly elevated plasma levels of citrulline and ammonia , caused by a deficiency of argininosuccinate synthetase in the liver . \n a small number of patients have undergone liver transplantation with favorable results . in korea , the limitations of the deceased donor pool have made living donor liver transplantation a common alternative treatment option . \n we report the case of a patient with type ii citrullinemia who was treated successfully with auxiliary partial orthotopic liver transplantation ( apolt ) from a living donor . \n this is the first description of an apolt for a patient with adult onset type ii citrullinemia in korea .", "id": 966} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nsialolithiasis is the most common disease of salivary glands caused by the obstruction of a salivary gland or its excretory duct by a calculus .\nit may occur at any age but there is a peak incidence in fourth , fifth , and sixth decades .\nmajority of salivary calculi ( 8095% ) occur in the submandibular gland , whereas only 520% are found in the parotid gland .\nsialoliths located in the duct are usually elongated , while those situated in the gland or hilus tend to be round or oval .\nthe size of the salivary calculi may vary from < 1 mm to a few cms in largest diameter .\nmost of the calculi ( 88% ) are < 10 mm in size , whereas only 7.6% are larger than 15 mm .\nthey consist of mainly calcium phosphate with smaller amounts of carbonates in the form of hydroxyapatite , with smaller amounts of magnesium , potassium , and ammonia .\na 45-year - old male reported to the outpatient department of vspm 's dcrc , nagpur , with the chief complaint of pain and swelling in the floor of mouth on the left side since 1 month .\ndetailed history revealed that it has started as a small swelling which used to increase before meals 1 month back .\nintraoral examination revealed a well - defined elongated swelling of approximately 2.5 cm 1 cm in size in the floor of the mouth in relation to lower left incisors to first molar region .\noverlying mucosa was inflamed and the swelling was hard in consistency and tender on palpation [ figure 1 ] .\nradiographic evaluation included cross - sectional mandibular occlusal view which revealed a large well - defined elongated homogenous radio - opacity in the floor of the mouth on the left side in relation to lower left canine to first molar region .\nit was approximately 2.5 cm 1.5 cm in size [ figure 2 ] . swelling in the floor of mouth on the left side mandibular occlusal radiograph showing submandibular salivary duct calculus on the basis of clinical and radiological findings\n, a diagnosis of left submandibular duct sialolith was made . as it was a large sialolith , we elected to remove the sialolith surgically under local anesthesia [ figure 3 ] .\nthe sialolith removed measured 25 mm ( i.e. 2.5 cm ) in length [ figure 4 ] .\nremoval of the sialolith from wharton 's duct the removed sialolith measured 2.5 cm 1.5 cm in its largest dimension\nthe sialolith was in the wharton 's duct and the patient had pain before and during meals . for stone formation\nit is likely that intermittent stasis produces a change in the mucoid element of saliva , which forms a gel .\nthis gel produces the framework for deposition of salts and organic substances creating a stone .\ntraditional theories suggest that the formation occurs in two phases : a central core and a layered periphery .\nthe central core is formed by the precipitation of salts , which are bound by certain organic substances .\nanother theory has proposed that an unknown metabolic phenomenon can increase the saliva bicarbonate content , which alters calcium phosphate solubility and leads to precipitation of calcium and phosphate ions . a retrograde theory for sialolithiasis has also been proposed .\naliments , substances , or bacteria within the oral cavity might migrate into the salivary ducts and become the nidus for further calcification .\nsalivary stagnation , increased alkalinity of saliva , infection or inflammation of the salivary duct or gland , and physical trauma to salivary duct or gland may predispose to calculus formation .\nsubmandibular sialolithiasis is more common as its saliva is ( i ) more alkaline , ( ii ) has an increased concentration of calcium and phosphate , and ( iii ) has a higher mucous content than saliva of the parotid and sublingual glands .\nin addition , the submandibular duct is longer and the gland has an antigravity flow .\nsialolithiasis typically causes pain and swelling of the involved salivary gland by obstructing the food - related surge of salivary secretion .\ncalculi may cause stasis of saliva , leading to bacterial ascent into the parenchyma of the gland and therefore infection , pain , and swelling of the gland at meal time .\nbimanual palpation of the floor of the mouth , in a posterior to anterior direction , reveals a palpable stone in a large number of cases of submandibular calculi formation and a uniformly firm and hard gland suggests a hypofunctional or nonfunctional gland .\nother traditional diagnostic methods include sialography , ultrasound , computed tomography , and scintigraphy for sialoliths .\nas the lesions were observed clearly in occlusal radiographs , no further investigations were performed for diagnosis .\nthe treatment objective for giant sialoliths , as for the standard - sized stones , is restoration of normal salivary secretion .\nthere are three ways in which we can treat patients with salivary stones : removal through the oral cavity , interventional sialoendoscopy , and resection of the gland .\nour choice depends on the site , size , shape , number , and quality of the stones .\nthe giant sialolith should be removed in a minimally invasive manner , via a transoral sialolithotomy , to avoid the morbidity associated with sialadenectomy . whenever the stone can be palpated intraorally , it is best to remove it through an intraoral approach . for giant sialoliths , transoralsialolithotomy with sialodochoplasty or sialadenectomy\nsubmandibular gland removal is indicated if ( 1 ) the gland has been damaged by recurrent infection and fibrosis , ( 2 ) there is a stone of substantial mass within the gland itself that is not surgically accessible intraorally , ( 3 ) there are small stones present in the vertical portion of wharton 's duct from the comma area to the hilum , ( 4 ) the size of an intraglandular stone reaches 12 mm or more as the success of lithotripsy may be < 20% in such cases .\nthere are various methods available for the management of salivary stones , depending on the gland affected and stone location .\ntransoral sialolithotomy remains mainstay of the treatment for giant sialolith in the duct of submandibular gland .\nalso , patients should be followed up regularly as recurrence has been reported in the literature .", "answer": "salivary gland calculi account for the most common disease of the salivary glands . \n most of the salivary calculi are small in size . \n some calculi that reach several centimeters are reported as megaliths or giant calculi in the literature . \n they may occur in any of the salivary gland ducts but are most common in wharton 's duct and in the submandibular gland . \n this report presents clinical and radiographical sign of an unusually large sialolith . \n a patient came with pain in the floor of mouth . \n there was a swelling on floor of mouth on the left side . \n radiographical examination revealed large irregular radio - opaque mass superimposed on left lateral incisor to molar areas . \n this case report describes a patient presenting with an unusually large submandibular gland duct sialolith , the subsequent patient management , the etiology , diagnosis , and its treatment .", "id": 967} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthese include the \n intrinsic flexor pollicis brevis , flexor pollicis longus , lumbricalis , flexor brevis , and \n flexor longus muscles1 .\ntoe - gripping \n strength is measured in the sitting position with the trunk vertical , the hip and knee \n joints at 90 , and the ankle joint in the neutral position1,2,3 .\nlow toe - gripping strength is a risk factor of falls for the \n elderly , and several studies have reported that toe - gripping strength is lower in subjects \n with a history of falls than in those with no history of falls1,2,3,4 .\nfurthermore , toe - gripping \n strength can be increased by training5 , \n which can decrease the risk of falls1 . \n\nsouma et al.6 studied the % iemg of \n several crural muscles ( the soleus muscle , medial head of the gastrocnemius muscle , and \n tibialis anterior ) during toe - gripping in 3 different ankle joint positions10 of plantar \n flexion and 0 and 10 of dorsiflexion and reported that the crural muscles help the ankle \n joint by co - contracting during toe - gripping . in another study ,\nnakae et al.7 calculated the % iemg of the same muscles \n during toe - gripping with subjects seated on the edge of a seat or standing , and reported \n that the % iemg of the medial gastrocnemius muscle was significantly lower when subjects were \n seated than when they were standing .\nhowever , as both studies focused on the activity of the \n crural muscles , the activity of the femoral muscles during toe - gripping remains unclear .\nwe \n believe it is important to elucidate the contribution of femoral muscles to toe - gripping \n strength . in the present study , we investigated femoral muscle activity during toe - gripping to \n examine the role of the femoral muscles in toe - gripping strength .\ntheir \n average ( mean sd ) age , height , and body weight were 20.6 1.0 years , 159.4 6.3 cm , and \n 51.8 5.8 kg , respectively .\nthis study was approved by the ethics committee for human \n research of tohoku fukushi university , and written informed consent was received from all of \n the subjects after the purpose of the study had been explained to them .\ntoe - gripping strength of the dominant toe and emg activity of the ipsilateral thigh were \n synchronously recorded to assess the activity of the rectus femoris and biceps femoris \n muscles .\ntoe - gripping strength was measured using a toe - gripping dynamometer ( t.k.k.3360 ; \n takei co , ltd , niigata , japan ) . as described by uritani8\n, the subjects were instructed to sit with their trunk in the \n vertical position , hip and knee joints at 90 , and ankle joints in the neutral position .\nafter a sufficient \n number of training trials and adequate rest , toe - gripping strength was measured twice and \n the maximal force was used in the analysis . for all subjects ,\nthe right toe was dominant \n ( defined as the toe used to kick a ball ) . to measure the maximum voluntary contraction ( mvc ) activity of the rectus femoris muscles , \n as described by kai9 ,\neach subject was \n instructed to sit on a chair with the hip and knee joints at 90 , and to exert maximal \n isometric force of knee extension while resisting an opposing force applied by the examiner . \n\nthe emg was recorded for 3 seconds while each subject exerted maximal force of knee \n extension . to measure the mvc of the biceps femoris muscle ,\neach subject was instructed to \n generate maximal isometric force of knee flexion while resisting an opposing force applied \n by the examiner .\nthe emg was recorded for 3 seconds while each subject exerted maximal force \n of knee flexion .\nafter confirmation of adequate skin preparation ( skin resistance of less \n than 5 k ) , three bipolar lead electrodes ( de-2.1 , delsys , inc . , boston , usa ) were attached \n to the skin over the rectus femoris and the long head of the biceps femoris , as described by \n peroto10 . for measurement of the rectus \n\nfemoris muscle , the electrode was attached at the midpoint between the superior edge of the \n patella and the anterior superior iliac spine . for measurement of the long head of the \n biceps femoris ,\nthe electrode was attached at the midpoint between the head of the fibula \n and ischial tuberosity .\nthe emg signal was collected using ml846 power lab 4/26 ( sample : 1,000 hz ; ad instruments \n co. , ltd . ) and transferred to a personal computer .\nthe bandwidth was 20500 hz . the emg \n signal segment selected and integrated ( integrated electromyogram : iemg ) for analysis was \n the middle 1 s of the entire 3-s duration of continuous maximal toe - gripping strength .\nthe iemg was analyzed using lab chart pro v7.3.5 ( ad instruments co. , ltd . ) and normalized \n to the iemg of each muscle s mvc .\nrepeated mann - whitney u tests were used to compare the % iemg of the \n rectus and biceps femoris muscles .\nrelationships between the % iemg of the rectus and biceps \n femoris muscles were statistically analyzed using spearman s correlation coefficient .\nthe average ( mean sd ) toe - gripping strength was 20.9 3.6 kg .\nthe average ( mean sd ) \n % iemg values of the rectus and biceps femoris muscles were 7.0% 6.2% and 25.6% 15.9% , \n respectively .\nthe % iemg of the biceps femoris was significantly higher than that of the \n rectus femoris ( p < 0.01 , table 1table 1.comparison of the % iemg values of the rectus femoris and biceps femoris muscles \n during toe - gripping actionrectus femorisbiceps femorismedian ( range : min max)median ( range : min max)%iemg4.8 * ( 1.521.1)27.2 ( 3.068.1)mann - whitney u test * : p < 0.05 ) .\nmann - whitney u test * : p < 0.05 using spearman s correlation coefficient analysis , a significant positive correlation was \n found between the % iemg of the rectus femoris and that of the biceps femoris ( r = 0.548 , p \n\nin the present study , we found that the % iemg of the biceps femoris was significantly \n higher than that of the rectus femoris .\nmoreover , a significant positive correlation was \n found between the % iemg of these two muscles .\nthese results suggest that femoral muscles \n co - contract during toe - gripping action , and thus possibly contribute to knee joint \n stability .\nwe found that toe - gripping action stimulates femoral muscle activity and that the % iemg of \n the biceps femoris was significantly higher than that of the rectus femoris .\nsato et \n al.11 reported that during \n toe - gripping , the tibialis anterior and soleus muscles are activated first , followed by the \n gradual activation of the medial head of the gastrocnemius muscle .\nthe biceps femoris \n initiates knee flexion , and the medial head of the gastrocnemius is a synergist for knee \n flexion .\nadditionally , active tension of the biceps femoris decreases during toe - gripping in \n knee flexion .\nthis may be because the length of the biceps femoris is shorter during active \n tension than during resting tension .\nwe think that the activation of the biceps femoris \n during toe - gripping was caused by increasing motor unit recruitment and synchronization of \n the impulse to compensate for decreasing activity of the biceps femoris . in the present study\n, we found a significant positive correlation between the % iemg of the \n rectus femoris and that of the biceps femoris .\nthis suggests that the % iemg of the rectus \n femoris increases with increases in the % iemg of the biceps femoris .\ntoe - gripping strength was measured using a closed kinetic chain movement , and therefore , \n the likelihood of movement in the directions of flexion or extension of the knee joint is \n less . however , because the gastrocnemius also acts on knee joint flexion during exertion of \n toe - gripping strength , the knee joint is readily displaced in the direction of flexion . to \n prevent this\n, it is thought that the knee joint is immobilized by contraction of the rectus \n femoris , that is , we think the rectus femoris during exertion of toe - gripping strength acts \n in order to control the action of knee joint flexion by the gastrocnemius .\nfirst , we were unable to avoid the common problems that \n negatively affect surface emg recording , such as skin resistance , artifacts , and the effects \n of proximal muscles .\nsecond , as only healthy young women participated in this study , it is \n difficult to extend our findings to the general population . in future studies\n, we need to \n consider this aspect , and involve healthy young men and individuals of different age \n groups .", "answer": "[ purpose ] in the present study , we investigated femoral muscle activity during \n toe - gripping , and the role of the femoral muscles in toe - gripping strength . \n [ subjects ] \n fourteen healthy young women were selected . \n [ methods ] we measured the maximum voluntary \n contraction of the rectus femoris and long head of the biceps femoris muscles . \n we then \n calculated the percent integrated emg ( % iemg ) during the toe - gripping action . \n [ results ] we \n found that the % iemg of the biceps femoris was significantly higher than that of the \n rectus femoris . \n moreover , a significant positive correlation was found between the % iemg \n of the rectus femoris and that of the biceps femoris . \n [ conclusion ] these results suggest \n that femoral muscles co - contract during the toe - gripping action , and thus possibly \n contribute to knee joint stability .", "id": 968} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nconfident peptide identification through tandem mass spectrometry ( ms ) is one of the most important components in ms - based proteomics .\nfor this reason , a great amount of effort has been invested to develop automated data analysis tools to identify peptides through tandem ms ( ms ) spectra . among available\nbecause each search method uses a different algorithm and proceeds from a different view of what spectrum components contain the most critical information for identification , the search results for one spectrum from various search engines may differ significantly .\nhowever , it is also well - recognized that such difference may be turned into positive use : it would be useful to find complementary engines and combine the results in an effective way to enhance peptide identification.(1 ) combining search results from different methods , if feasible , definitely bears the possibility to improve the peptide identification confidence via reducing noise and utilizing complementary strengths .\nthe difficulty in combining results from different search methods largely comes from the lack of a common statistical standard.(2 ) the importance of having a community standard has been stressed , and efforts in reaching such community standard have been invested . using iterative expectation - maximization ( em ) , keller et al .\n( 3 ) proposed a statistical model to estimate the probability , determined through a global analysis of ms spectra from an experiment , for a given spectrum to have correct peptide identification . in principle , results from different search methods may go through the same analysis and thus compared . however , if after the statistical analysis two different methods report different confident identifications for the same spectrum , one ends up needing to invent an ad hoc rule to decide which identification should be kept .\nfurthermore , to use the em approach , one needs to assume or guess , without theoretical / statistical foundation , the forms of the score distributions for true positives and false positives .\nthis , unfortunately , must weaken the validity of any statistical significance assignment obtained from such type of analyses . in our recent work,(4 ) it was shown possible to calibrate the statistics ( e - value ) of various search methods to reach a universal standard that is in agreement with the fundamental definition of e - value . for a given query spectrum and quality score cutoff s , e - value\nis defined as the expected number of hits , in a random database , with quality score being the same as or larger than the cutoff .\na realistic e - value assignment thus provides the user with the number of false positives to anticipate when setting a quality score threshold .\nmost importantly , this peptide - centric statistical calibration allows one to combine search results even if the top hits from various methods disagree . another possible approach\nto establish common statistical standard is through equating the false discovery rate ( fdr ) ( 5 ) of various methods considered .\nthis approach , however , does not provide statistical significance for each peptide hit and thus is not directly applicable to peptide - centric combination of different search results . to be explicit\n, one may refer from fdr the e - value of a peptide hit with score identical to the first false positive , but any peptide hits with score better than the first false positive can not have their e - value assigned .\nfurthermore , for peptides with scores falling in the range [ sk+1 , sk ] , where sk represents the kth best score of false positives , one can not distinguish them statistically well except by using some ad hoc interpolations .\nthere also exist other issues concerning misleading inference using fdr , but this is not the focus of the current paper and we refer the readers to a few relevant literatures . in this paper , in addition to providing a universal protocol to combine search results , we also carry out the performance assessment for all possible combinations , among seven database search methods , of two and three search methods using the receiver operating characteristic ( roc ) curves .\nthe database search methods employed in our analysis are sequest(8 ) ( v27 rev12 ) , probid(9 ) ( v1.0 ) , inspect(10 ) ( v20060505 ) , mascot(11 ) ( v2.1 ) , x !\ntandem(12 ) ( v2007.07.01.2 ) , omssa(13 ) ( v2.0 ) and raid_dbs.(14 ) to better illustrate the main points of this paper , we have relegated to the supporting information a large number of roc curves that convey similar information of that exhibited in the plots of the main text .\nsince the centroid mode seems to be the dominant mode in ms database searches today , we present in the main text only results from centroid mode data and results from profile mode data are shown in the . throughout the paper ,\nwe use dalton ( da ) as the unit for molecular weight . in the following ,\nwe will then describe briefly in the implementation , followed by our main results : best combinations within search methods tested .\nin this section , we will start with the definitions of p - value and e - value , which will be frequently used for the rest of this paper .\nwe then describe the mathematical underpinnings of how to combine the p - values of different database search methods to result in a final e - value .\nwe should note that the mathematical formulation employed here was first introduced by fisher,(15 ) and its extensions and applications to other research areas also exist . to the proteomics community\nlet us define the p - value and e - value in the context of peptide identification in database searches .\nfor a given spectrum and a score cutoff sc , one may ask what is the probability for a qualified ( with molecular weight in the allowed range ) random peptide to reach a score larger than or equal to sc .\nthis probability p(sc ) , a function of sc , is called the p - value . for spectrum\n , if a database contains n qualified , unrelated random peptides , one will expect to have e(sc ) = np(sc ) number of random peptides to have quality score larger than or equal to sc .\nthis expectation value e(sc ) is by definition the e - value associated with score cutoff sc .\nif one further assumes that the occurrence of a high - scoring random hit is a rare event and thus can be modeled by a poisson process with expected number of occurrence e(sc ) , one may then define another p - value , which is called the database p - value , via \n\n the database p - value pdb(sc ) represents the probability of seeing at least one hit in a given random database with quality score larger than or equal to sc .\nnote that , at the level of pdb , one may compare the statistics from different search methods using different sizes of random databases .\nbecause of the differences in the choices of optimal search parameters , it is likely that different search methods , for the same query spectrum , may search over different number of qualified peptides , that is , having different effective database sizes\n. therefore , combining the database p - values is the natural choice if one were to merge results from different search methods .\nsuppose that one wishes to combine the search results from l different search methods , each peptide candidate will have in principle l different p - values reported by the l search methods .\nthe formula in eq 6 of the next subsection provides us the final combined p - value pcomb from the list .\nonce pcomb is obtained , we may invert the formula in eq 1 to get a combined e - value ecomb via \n\n having outlined how to obtain the final quantity of interest , ecomb , we now turn to the mathematical underpinnings of how to combine a list of , ideally independent , p - values reported by different database search methods .\nconsider an event labeled by a list of l independent quantities s1 , s2 , ... , sl . each quantity si may have an associated p - value pi depending on the statistics of the variable si .\nan important issue to address is how one should combine all the pi values to obtain an overall p - value . in the context of combining search results of different methods to assign statistical significance to a certain candidate peptide \npl ) uniformly distributed in the interval ( 0 , 1 ) ] , what is the probability of finding their product to be smaller than a certain threshold . to put it in a more concrete framework , one may consider a unit hypercube whose interior points having coordinates ( x1 , x2 , ... , xl ) with 0 xi 1 for all 1 \ni l. one then asks what is the volume bounded by the hypersurfaces xi 0 and ( i=1lxi ) with = i=1lpi .\nwe may express this volume f( ) mathematically as an integral : \n\n where (x ) is a step function with (x > 0 ) = 1 and (x < 0 ) = 0 .\nlet f( ) f()/ , we have \n\n with (x ) being the dirac delta function that takes zero value everywhere except when x = 0 where its value approaches infinity .\nfor the ease of computation , we make the following changes of variables : e and xi e. after this change , all the new variables t and ui are in the range ( 0, ) .\nequation 4 now becomes ( with = e understood ) \n\n where the identity (e e ) = e(t c ) is used . using the integral expression of the delta function\n, \n\n we may rewrite eq 4 as ( with = e understood ) \n\n where the last equality results from choosing the integration path to enclose the lower half of the complex k plane .\nwe may now go back to f( ) by integrating f( ) . \n\n with \n= i=1lpi while combining the lp - values p1 , p2 , ... , pl . as specific examples , when l = 2 , we have f(p1p2 ) = p1p2[1 ln ( p1p2 ) ] , and when l = 3 , we have f(p1p2p3 ) = p1p2p3[1 ln(p1p2p3 ) + ln(p1p2p3 ) ]\n. we will provide in the more examples to elucidate the consequence of the formula provided in eq 6 .", "answer": "confident peptide identification is one of the most important components in mass - spectrometry - based proteomics . \n we propose a method to properly combine the results from different database search methods to enhance the accuracy of peptide identifications . \n the database search methods included in our analysis are sequest ( v27 rev12 ) , probid ( v1.0 ) , inspect ( v20060505 ) , mascot ( v2.1 ) , x ! tandem ( v2007.07.01.2 ) , omssa ( v2.0 ) and raid_dbs . using two data sets , one collected in profile mode and one collected in centroid mode , we tested the search performance of all 21 combinations of two search methods as well as all 35 possible combinations of three search methods . \n the results obtained from our study suggest that properly combining search methods does improve retrieval accuracy . \n in addition to performance results , we also describe the theoretical framework which in principle allows one to combine many independent scoring methods including de novo sequencing and spectral library searches . the correlations among different methods are also investigated in terms of common true positives , common false positives , and a global analysis . \n we find that the average correlation strength , between any pairwise combination of the seven methods studied , is usually smaller than the associated standard error . \n this indicates only weak correlation may be present among different methods and validates our approach in combining the search results . \n the usefulness of our approach is further confirmed by showing that the average cumulative number of false positive peptides agrees reasonably well with the combined e - value . \n the data related to this study are freely available upon request .", "id": 969} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe included 3,615 french men and women , aged 3065 years , with baseline fasting glycemia ( fg )\n< 6.1 mmol / l , who participated in the 9-year follow - up d.e.s.i.r .\nparticipants provided written informed consent , and the protocol was approved by the ethics committee of bictre hospital , kremlin - bictre , france .\nincident hyperglycemia was identified by an fg 6.1 mmol / l or treatment for diabetes , and incident diabetes was identified by an fg 7.0 mmol / l or treatment of diabetes during at least one of the three follow - up examinations ( years 3 , 6 , and 9 ) .\nsmoking , dietary habits , degree of physical activity , and alcohol consumption were assessed using a self - administered questionnaire .\nmean daily intake of water , wine , beer or cider , and sweet beverages was categorized in the questionnaire into six mutually exclusive levels : none , < 0.5 , 0.5 to 1 , 1 to 1.5 , 1.5 to 2.0 , and > 2 l. in the present analyses , the levels were grouped into three classes : < 0.5 , 0.5 to 1 , and > 1 l. other clinical and biological measurements are presented in the supplementary methods .\nresults are presented as means ( sd ) or median ( 25th75th percentiles ) for quantitative variables and as percentages for qualitative variables .\nbaseline means and percentages were compared between the three w - intake classes using anova or tests .\nlogistic regression models were used to determine odds ratios ( ors ) and 95% cis corresponding to the comparison of incident hyperglycemia in middle and high classes of w - intake in comparison with the lowest class .\nadjustment variables were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .\nwe included 3,615 french men and women , aged 3065 years , with baseline fasting glycemia ( fg )\n< 6.1 mmol / l , who participated in the 9-year follow - up d.e.s.i.r .\nparticipants provided written informed consent , and the protocol was approved by the ethics committee of bictre hospital , kremlin - bictre , france .\nincident hyperglycemia was identified by an fg 6.1 mmol / l or treatment for diabetes , and incident diabetes was identified by an fg 7.0 mmol / l or treatment of diabetes during at least one of the three follow - up examinations ( years 3 , 6 , and 9 ) .\nsmoking , dietary habits , degree of physical activity , and alcohol consumption were assessed using a self - administered questionnaire .\nmean daily intake of water , wine , beer or cider , and sweet beverages was categorized in the questionnaire into six mutually exclusive levels : none , < 0.5 , 0.5 to 1 , 1 to 1.5 , 1.5 to 2.0 , and > 2 l. in the present analyses , the levels were grouped into three classes : < 0.5 , 0.5 to 1 , and > 1 l. other clinical and biological measurements are presented in the supplementary methods .\nresults are presented as means ( sd ) or median ( 25th75th percentiles ) for quantitative variables and as percentages for qualitative variables .\nbaseline means and percentages were compared between the three w - intake classes using anova or tests .\nlogistic regression models were used to determine odds ratios ( ors ) and 95% cis corresponding to the comparison of incident hyperglycemia in middle and high classes of w - intake in comparison with the lowest class .\nadjustment variables were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .\nbaseline characteristics of the 3,615 normoglycemic participants are presented according to their class of w - intake ( table 1 ) . among them , during follow - up , 565 subjects became hyperglycemic and 202 developed diabetes .\nthe daily w - intake was negatively associated with the risk of new - onset hyperglycemia , even after adjustment for multiple metabolic risk factors .\ncompared with daily w - intake of < 0.5 l , ors were 0.64 ( 95% ci 0.490.83 ) and 0.73 ( 0.550.97 ) for classes of 0.51.0 l and > 1.0 l , respectively ( p = 0.003 ) .\nafter further adjustments for intake of other beverages , the ors were slightly attenuated : 0.68 ( 0.520.89 ) and 0.79 ( 0.591.05 ) for classes of 0.51.0 l and > 1.0 l , respectively ( p = 0.016 ) ( table 1 ) .\nwith the two upper classes combined , the or was 0.72 ( 0.560.92 ) ( supplementary fig .\n1 ) . there was no interaction with several important characteristics , including those related to self - reported alcohol or tobacco consumption ( supplementary table 1 ) .\nbaseline characteristics of the study population and risk for new - onset hyperglycemia during follow - up , by classes of mean daily w - intake data are means ( sd ) or medians ( 25th75th percentiles ) for continuous variables and percentages of patients for categorical variables .\nthzd , thiazidic diuretics ; furo , furosemide ; homa - ir , homeostatic model assessment index of insulin resistance ; homa - b , homeostatic model assessment index of insulin secretion\n. hypertension was defined as systolic or diastolic blood pressure > 140 or 90 , respectively , or treated with antihypertensive drugs .\nors ( 95% cis ) for the association between daily w - intake at baseline and the risk of incident hyperglycemia ( fasting plasma glucose 6.1 mmol / l or treatment for diabetes ) are presented according to two statistical models ; variables for adjustment were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .\nmodel 1 : adjusted for age , sex , bmi , baseline fg , physical activity , smoking status , triglycerides , homa - ir , and total cholesterol .\nmodel 2 : further adjusted on self - reported intake of other fluids ( i.e. , volumes of beer or cider , sweet drinks , and wine consumed per day ) .\nthe c - reactive protein was available for only 181 , 466 , and 333 subjects in the three classes of w - intake , respectively . * * hdl cholesterol and ldl cholesterol were not available for 28 and 26 subjects , respectively . the same trend , although nonsignificant , was observed for the association with new - onset diabetes : compared with participants with a daily w - intake < 0.5 l , ors for those drinking 0.51.0\nl and > 1.0 l water per day were 0.68 ( 95% ci 0.411.15 ) and 0.75 ( 0.431.32 ) , respectively , p = 0.36 .\nrisk for hyperglycemia was negatively and independently related with self - reported w - intake in normoglycemic middle - aged individuals from the french general population\nhowever , the association was moderately attenuated when important metabolic risk factors and potential confounders were introduced as covariables in the analysis , including intake of other classes of beverages with known adverse long - term effects ( sweet and alcohol - containing drinks ) .\nour data support the novel idea that vasopressin , besides its role in urine concentration , is also an important actor in glucose homeostasis ( 1 ) .\nthe negative association of w - intake and risk for hyperglycemia was relevant among many subsets of participants , and those reporting a low w - intake ( < 0.5 l ) had a higher risk for hyperglycemia ( for example , participants in the high physical activity group ) ( supplementary table 1 ) . this indicates that identification of individuals with a w - intake of < 0.5 l may be widely relevant to target preventive interventions regarding the metabolic risk .\ndiabetes incidence was low and statistical power was thus limited ; 24-h urine volume was not measured , but the urinary density was inversely associated with self - reported w - intake , arguing for the validity of the questionnaire ( table 1 ) . in addition , we can not exclude residual confounding : healthier behaviors correlating with higher water drinking could account for the observed association .\nfinally , only volunteers were included and the results may not be extrapolated to the general population . knowing the rise of vasopressin in diabetes , its effect on glycemia , gluconeogenesis , and glucagon release , it is surprising that no attention had been given to vasopressin as a possible risk factor for hyperglycemia and diabetes until a recent report of an association between copeptin and the incidence of diabetes ( 1,4,5,14 ) .\nour study extends this observation , drawing attention to a low w - intake as a possible new risk factor for impaired glycemia .\nit suggests that an increase in w - intake , an easy and costless intervention , could prevent or delay the onset of hyperglycemia and subsequent diabetes .\nhopefully , our study will serve as a benchmark to design appropriate clinical trials testing the efficacy of this intervention in people who report drinking < 0.5 l of water per day , as did almost 20% of the participants in this cohort .", "answer": "objectivewater intake alters vasopressin secretion . \n recent findings reveal an independent association between plasma copeptin , a surrogate for vasopressin , and risk of diabetes.research design and methodsparticipants were 3,615 middle - aged men and women , with normal baseline fasting glycemia ( fg ) , who were recruited in a 9-year follow - up study . \n odds ratios ( ors ) and 95% cis for the incidence of hyperglycemia ( fg 6.1 \n mmol / l or treatment for diabetes ) were calculated according to daily water intake classes based on a self - administered questionnaire.resultsduring follow - up , there were 565 incident cases of hyperglycemia . after adjustment for confounding factors , ors ( 95% cis ) for hyperglycemia associated with classes of water intake ( < 0.5 l , n = 677 ; 0.5 to < 1.0 \n l , n = 1,754 ; and > 1.0 l , n = 1,184 ) were 1.00 , 0.68 ( 0.520.89 ) , and 0.79 ( 0.591.05 ) , respectively ( p = 0.016).conclusionsself - reported water intake was inversely and independently associated with the risk of developing hyperglycemia .", "id": 970} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nnowadays cardiac surgeons must face the problem of severely impaired left ventricle function almost on a daily basis .\nheart transplantation , due to the limited donor pool , can be offered only to a small number of patients suffering from cardiac failure [ 1 , 2 ] . furthermore , the idea of long - term mechanical support as a destination therapy is still evolving .\nhence , efforts to optimize the results of routine cardiac surgery have to be undertaken . in a properly selected group of patients coronary surgery alone or combined with mitral surgery can improve both quality of life and long - term survival .\nwith borderline ventricular function prior to surgery this may result in failed weaning from cardiopulmonary bypass .\nin isolated coronary surgery beating heart strategy , either on or off pump seems to be a safer option .\nits use however is hardly possible when mitral valve repair or replacement needs to be done .\nintra - aortic balloon pump ( iabp ) is a gold standard here , but some patients may require more sophisticated mechanical assistance [ 3 , 4 ] .\nthe idea of short - term , perioperative mechanical support , preferably with a low anticoagulation regime , looks very convenient in this respect .\nimpella microaxial pumps ( abiomed europe gmbh , aachen , germany ) seem to meet these criteria .\nthey use the idea of pulling the blood from the left ventricle into the aorta , which is accomplished by means of a rotating impeller positioned in the aorta with the tip of the device and inlet area positioned in the left ventricle .\nthis results in reduction of both left ventricle end diastolic volume ( lvedv ) and left ventricle end diastolic pressure ( lvedp ) . the systemic pressure and flow are increased .\nthe less stretched left ventricle , with better subendocardial perfusion , has more time to recover . on the other hand ,\nthe impella pump can be applied either by cardiologists ( impella 2.5/impella cp ) in a cath lab setting or by cardiac surgeons ( impella 5.0/impella ld ) in an operating theatre with either peripheral vascular or central direct access . offering flow up to 5 l / min ,\nthe anticoagulation management requires only heparin infusion to keep activated clotting time ( act ) not shorter than 160 s. thanks to the automated controller with an intuitive , user friendly interface , operating the device can be easily mastered by doctors and nursing staff .\na 64-year - old woman suffering from ischemic dilated cardiomyopathy associated with mitral insufficiency was referred for combined treatment consisting of resynchronisation therapy followed by simultaneous coronary and mitral surgery .\ninitial echocardiography revealed impaired global contractility ( ejection fraction [ ef ] 10 - 15% ) , dilated left ventricle ( left ventricle end diastolic diameter [ lvedd ] 7.8 cm ) , significant ventricular asynchrony ( 50 ms ) and moderate mitral regurgitation ( vena contracta [ vc ] 6 mm ) due to both restriction of the posterior leaflet and dilation of the mitral annulus ( 5.5 cm ) .\nthere were no significant abnormalities regarding the right ventricle , pulmonary valve and tricuspid valve .\nclinically the patient presented with end stage cardiac failure including resting dyspnea ( nyha iv ) .\nthe patient underwent uneventful implantation of an icd crd ( maximo ii ) , which resulted in improved exercise tolerance .\nthis was consistent with post - procedure echocardiography showing no significant ventricular asynchrony ( 4 ms ) , slightly improved contractility ( ef 20% ) and unchanged moderate mitral regurgitation ( vc 6 mm ) .\ntherefore the patient was referred for combined cardiac surgery including mitral repair and coronary grafting .\nbecause of poor lv function and the complexity of the procedure , it was decided to apply short - term mechanical support during and after surgery .\nthe impella ld microaxial pump was chosen due to the simplicity of implantation and the low anticoagulation regime . also , the impella ld does not require a hybrid theater with fluoroscopic guidance .\nantegrade cold blood cardioplegic solution was administered through the aortic root . the posterior descending artery ( pda ) and left anterior descending artery ( lad ) were grafted with the long saphenous vein and left internal thoracic artery respectively .\nthe left atrium was entered in a routine manner after dissecting sondergaard 's plane . on inspection the echocardiographic findings were confirmed .\nthe only surgical issue was severe atherosclerosis of the ascending aorta affecting both anastomosis of the vein graft and implantation of the impella device . before the implantation\na 10 mm dacron graft was anastomosed to the ascending aorta using a side biting clamp ( fig .\nthe impella catheter was inserted through the graft and then , under transesophageal echocardiographic ( tee ) guidance , was forwarded through the ascending aorta and the aortic valve into the left ventricle ( figs . 2 and 3 ) . immediately after confirming the position the impeller rotation was initialized .\nmeticulous attention was paid to maintain proper left ventricle volume preloading in order to avoid pump malfunction . after securing hemostasis\nthe chest was closed , letting the driveline out above the suprasternal notch and through the upper end of the sternotomy wound .\nthe patient was transferred to intensive treatment unit ( itu ) in a stable condition .\nthere she was kept sedated and ventilated electively . therapeutic activated clotting time ( act )\nthe position of the pump was checked daily and in case of any suspicion of malfunction .\nadequate flow was maintained most of the time , with one episode of stopping of the machine , which was easily managed with fluid infusion .\nthe inotropic support was reduced gradually without affecting hemodynamic stability . on the 2 postoperative day\nthe further postoperative course was mainly uneventful , although prolonged mechanical ventilation was required ( 8 days ) .\nthe first follow - up visit two months after discharge confirmed good exercise tolerance and satisfactory echocardiographic findings ( trace mitral regurgitation , lvedd 7.6 cm , ef 25% ) .\nimpella device inserted through the tubing graft anastomosed to the ascending aorta impella device in the ascending aorta , approaching the aortic valve impella device finally positioned in the left ventricle doppler scan showing the flow from the left atrium to the left ventricle ( blue ) and within the device from the left ventricle to the aorta ( red )\npatients with impaired left ventricle function require a particular surgical strategy . obviously , it is crucial to perform a routine procedure such as coronary grafting or valve surgery with meticulous surgical technique and good timing .\ntherefore , these patients should be operated on by senior surgeons . however , even in experienced hands , such cases may prove quite tricky .\nsometimes , even perfect coronary anastomoses and the shortest ischemic time can not prevent failed weaning from cardiopulmonary bypass . the possibility of perioperative mechanical support , exceeding the intra - aortic balloon pump , is quite tempting .\none option is extracorporeal membrane oxygenation ( ecmo ) , which can support the circulation for up to a few weeks .\nthis requires , however , both arterial and venous cannulation , an aggressive anticoagulation regime and specially trained perfusionists and nursing staff .\nextracorporeal membrane oxygenation is also associated with a long list of potential complications including infection , bleeding , thromboembolic events , hemolysis and finally multiorgan failure ( mof ) .\nthere is no doubt that ecmo is a well - established and recognized life - saving procedure ; however , the question may be raised whether some patients could benefit from an easier technology used in a planned manner .\n, there is quite a wide range of indications for their use , two in cardiology : as a rescue treatment in cardiogenic shock caused mainly by acute coronary syndrome and , electively , as a support in high - risk percutaneous interventions including pci and vt ablation [ 7 , 8 ] . because of endovascular insertion and therefore limited device size ( 12 fr )\nthe generated flow can not be higher than 2.5 l / min , which usually is enough in the above situations .\nimpella pumps may be applied in post - cardiotomy shock when an intra - aortic balloon is not enough to succeed in weaning from cardiopulmonary bypass .\ncardiac surgeons may also use them more electively as a perioperative support in patients with significantly impaired left ventricular function .\nthe surgical insertion can be performed either peripherally ( impella 5.0 ) or directly through the ascending aorta ( impella ld ) . in peripheral access\nthe femoral or axillary artery is exposed , then the device is inserted using a tubing graft and forwarded to the left ventricle under fluoroscopic guidance .\nthe hybrid theatre setting is required , but on the other hand it is possible to perform less invasive , thoracoscopic surgery . in direct access , after sternotomy , the implantation is quite easy under tee guidance .\nwhatever the access , the surgical technique allows one to insert a bigger device ( 21 fr ) , which is able to generate flow up to 5 l / min ( ! ) .\nthat means that after the procedure , which is slightly more complex than insertion of an iabp , and having a device which is almost as easy to operate as an iabp , we achieve an effect that is very close to the benefit of left ventricular assist device ( lvad ) .\nthe aforementioned problem of left ventricle venting is solved by definition , with impella being an intraventricular device .\nit should not stay in for longer than 5 days , which is more than enough to rethink and rearrange a new strategy .\n( impella , ecmo , lvad , recovery or transplant ) . when it is applied electively , as in our case , the chances are very high that only the first stage will be necessary .\nthis being the case , the impella pump can be deservedly regarded as a short bridge to recovery .", "answer": "cardiac surgeons have to face the problem of impaired left ventricle function in patients undergoing routine valve or coronary procedures . \n the intra - aortic balloon pump is not always effective in preventing cardiac failure . \n the idea of using a microaxial rotating pump as a short - term perioperative support seems to be a convenient solution . \n the case of a patient with dilated cardiomyopathy undergoing combined mitral and coronary surgery with elective use of the impella ld pump is presented . \n various options of applying the impella device are discussed , especially as a bridge to transplant or bridge to recovery .", "id": 971} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe study was conducted at an intensive 4-day teaching program for final - year ophthalmology residents , held at hubli , karnataka state , south india , in january 2014 .\nthe questionnaire used in this survey was developed and validated in consultation with the division of research and patents of the parent institute of the chief author .\nthe questionnaire contained 21 questions ( appendix 1 ) , eliciting information from the students about orientation and wet lab training received , operation theatre ( ot ) facilities for training , free surgical camps and detailed information about numbers and types of surgeries observed and performed ; also , questions about what factors influenced the student to pursue ophthalmology residency , about future plans after finishing residency , and if considering fellowship training after residency , which sub - specialties were preferred .\nidentity information like name was not solicited , and the students were free to not participate in the survey by simply not returning the form . to ensure increased response rate , the students were counseled about the objectives and importance of the survey during the training program .\nrepeated announcements were made on each day of the training program requesting students to return completed forms .\none hundred and thirteen residents participated in the survey by returning completed forms ( 72.9% ) .\nsix respondents were found to be 1 year postgraduates ( number of completed months of residency being < 12 ) and were excluded from further analysis in the survey .\nthe state - wise break - up of students was 76 from karnataka ( 71.02% ) , 16 maharashtra ( 14.95% ) , 8 tamil nadu ( 7.47% ) , 5 andhra pradesh ( 4.67% ) and 2 kerala ( 1.86% ) . the results of this survey , therefore , present a picture mainly from karnataka state and southern india .\ntwenty - four students were from a government medical college ( 22.42% ) , 38 from private medical colleges ( 35.51% ) , 22 from private eye hospitals ( 20.56% ) and 23 from other hospitals ( 21.49% ) .\nresidents ( 39.25% ) , 35 were dnb ( 32.71% ) and 30 were diploma residents ( 28.03% ) .\nthirty - nine students ( 36.5% ) chose got seat in the subject through entrance examination as the most important factor which influenced the decision to pursue ophthalmology residency .\nthirty - six students ( 33.6% ) mentioned offers chance of combined medical and surgical practice as the most important factor .\neleven students ( 10.3% ) mentioned workload predictability / flexibility , while positive undergraduate experience made seven students ( 6.5% ) choose ophthalmology .\n( 5 students , 4.6% ) and earning potential ( 2 students , 1.8% ) .\nforty - one students ( 38.31% ) received orientation / training about ophthalmic surgery / ot .\nsixteen of the 41 students ( 39.02% ) had received such orientation from their senior postgraduate / resident , 11 students ( 26.82% ) from senior faculty and 4 students ( 9.75% ) from junior faculty .\nsixty - one students ( 57.00% ) had undergone wet lab / simulation lab training .\nfifty - six students ( 52.33% ) had attended the wet lab training in their own college / hospital , and five had attended wet lab training in conferences .\neighteen students ( 16.82% ) mentioned that the ot in their center had no closed - circuit television facility for relaying surgical procedures while 37 students ( 34.57% ) mentioned that their ot did not have a microscope with observer arm .\nseventy students ( 65.42% ) did their first surgery in ophthalmic residency within the first 6 months , and 34 ( 31.77% ) students did so before the end of the 1 year .\ntwenty - six students ( 24.29% ) mentioned that free ophthalmic surgical camps were not held in their center . on an average ,\n45 students ( 42.05% ) went to the ot 2 times a week and 43 students ( 40.18% ) went 3 times a week .\nthe details of number of different types of surgeries done per week in the training center of the student , and median and range of number of surgeries done by the student so far are given in tables 1 and 2 .\nthe number of surgeries done per week in the training center of the students median and range of number of surgeries done per month at training centers and median and range of number of surgeries done by the students so far .\nmedian has been used as measure of central tendency instead of mean , as there are outlier values eighty - eight students ( 82.2% ) mentioned join fellowship ( or further training ) as the future plan after finishing residency .\nsix students ( 5.6% ) wanted to join government service and 3 ( 2.8% ) students wanted to join private service after finishing residency . joining medical college in the teaching profession and\n start own practice was chosen as the next step after residency by two students ( 1.8% ) each .\nof the 88 students considering fellowship / further training , 37 students ( 42.5% ) mentioned cataract surgery as the most preferred subject and 17 students ( 19.5% ) mentioned cornea / anterior segment .\nthirteen students ( 14.9% ) preferred vitreoretina / posterior segment and seven students ( 8.0% ) were considering further training in general ophthalmology .\nglaucoma and orbit / oculoplasty were being considered by 6 ( 6.9% ) and five students ( 5.7% ) respectively .\nstrabismus / pediatric ophthalmology was the first choice for two students ( 2.2% ) while none mentioned uveitis as the preferred subject for further training .\nthe final question of the survey regarded satisfaction of the student with the surgical training during residency .\nsix students ( 5.6% ) were very satisfied and 20 students ( 18.7% ) were satisfied with their surgical training while 37 students ( 34.6% ) found their surgical training during residency to be fair / average . \ntotally , 29 students ( 27.1% ) were not satisfied with their surgical training and 15 students ( 14.0% ) rated their surgical training as poor . \nthis survey with completed responses from 107 final - year residents provides us with a wealth of knowledge on the present status of surgical training in residency , especially in karnataka state and southern india , and on the immediate future plans of these residents .\nthe residents surveyed in this study were from all types of training institutes in the region , including government and private medical colleges , and private eye hospitals and general hospitals .\nless than a quarter of the students had received formal orientation training about ophthalmic surgery from their faculty .\nteachers , in their personal capacity , may be teaching students and explaining surgical principles while in the ot , but a formal orientation / training before the student enters the ot will be of benefit and is also desired by the student , as documented by a survey published in indian journal of ophthalmology .\nophthalmic conferences across india have been providing wet lab training for residents , but only a few students in this survey had attended one such .\nmore students can be encouraged to undergo such training and training institutes can help improve ophthalmic surgical training by establishing wet labs in their centers .\nmore than a third of the students were training in centers , where the ot did not have a microscope with observer arm ( beam - splitter and assistant scope ) .\nthe value of such equipment in the ot of a training institute would be immensely beneficial . the vast majority of training centers conducted free ophthalmic surgical camps for patients , as per this survey .\nmost of the residents surveyed in this study went to the ot more than once a week . these can be termed as desirable statistics .\nanother statistic which could be termed desirable would be that nearly every student performed his / her first ophthalmic surgery before the end of the 1 year of residency .\nthis compares favorably with the results of a survey of 129 ophthalmology residency directors in the united states , which had reported that 40% of residents gained experience as primary surgeons during their 1 year and 43% performed only part of the surgery .\nwhen exactly a resident starts his first surgery is dependent on many factors , including personality , temperament and natural , surgical aptitude of the resident , as well as the trainer 's considered judgment about the resident 's readiness to operate . in this\nregard , both residents and trainers will find extremely informative kirby 's excellent treatise on surgical technique for residents in ophthalmology , published in 1983 , but still relevant in this era for its sheer wisdom and understanding of teaching and learning methods of ophthalmic surgical techniques .\napproximately a third of the respondents indicated that the total number of surgeries done per week in their center is < 20 . increasing the number of operations per week is as much an administrative and logistic issue\nas a medical issue and lies under the purview of the respective training institutions , but higher numbers would obviously be desirable for the broader experience and exposure that would be provided . in our country , conducting free ophthalmic camps for the needy can be a win - win situation for ophthalmic care - givers and patients .\nneedy patients receive quality medical care at the hands of the teachers , which they may not otherwise be able to access , and they act as the providers of exposure and experience to the resident training under the teacher .\nconducting such camps will also help increase number of operations done per week in the training center .\nmost of the students had performed manual small incision cataract surgery ( msics ) , and this was also the surgery performed most commonly by the students table 2 .\nan analysis of table 2 shows that the median value of students responses to performance of surgeries other than msics was zero for all surgeries excluding pterygium ( 5 ) , dacryocystectomy ( 2 ) and trauma repair ( 5 ) . increasing the number of noncataract surgeries done by residents\nquestions 19 and 20 of the survey attempted to read the mind of the student regarding his / her immediate future . a huge majority planned to undergo further training , with cataract surgery and cornea / anterior segment being the most sought after subjects .\nit appears that most of the students would prefer to delay further the decision on practice till they are confident of their surgical skills .\na quarter of the respondents in this survey were satisfied with their surgical training while a significant number , more than 40% , were not satisfied with the surgical training during their residency . a brazilian study published in 2013 on recent ophthalmology graduates reported 93.4% satisfaction with the acquisition of surgical skills during residency .\nimproving satisfaction of residents with their surgical training should become an important goal of trainers .\nmore than a third of the students in this survey indicated that the most important factor influencing their decision to pursue ophthalmology residency was that they were allotted to the subject through the entrance examination .\na survey of junior residents in saudi arabia had found that the main factor influencing the decision to pursue ophthalmology training ( 97% of the respondents ) was the ability to combine medicine and surgery .\nthis meant that in our survey , a significant chunk of the students were doing residency in ophthalmology but had not come in desiring the subject specifically .\nif a student has come in because he had no perceived better choice , and subsequently , if he also feels that training being received is unsatisfactory , he may then find it difficult to involve himself in the subject , understand the subject and develop a liking for it .\nthis can prevent the student from reaching his full potential , as he simply does not like what he is doing . training accomplished with modern standards with an aim to also satisfy the students expectations ,\npositive under - graduate experience , family influence and earning potential .\n improving the experience of under - graduate medical students in their ophthalmology training may motivate more students to take up the field ; such motivated students are also likely to strive to improve their own personal learning and satisfaction .\nfinally , though the study achieved a fairly good response rate ( 72.9% ) , the nonresponse fraction may have an influence on the inferences and conclusions .\nthe limitations of this study include selection bias owing to purposive sampling , which might influence the results and subsequent conclusions .\nophthalmology residents in the region of karnataka and southern india are performing surgeries on a live human eye within the 1 year of residency and are entering the ot for surgery multiple times a week .\nfurther efforts from trainers can concentrate on adding to the quality of surgical training along with the quantity , by establishing more wet labs / simulation training programs , conducting formal orientation programs for residents before they start surgery and by promoting microscopes with observer arms and closed - circuit television facility . increasing the numbers of noncataract surgeries performed by residents and enhancing satisfaction levels of residents with their surgical training", "answer": "settings and design : this study documents a survey of final - year ophthalmology postgraduates on the subject of their surgical training and their future plans after residency.purpose:this survey aimed to answer the question , what is the present status of surgical training in ophthalmic training centers ? by obtaining information from students about ( 1 ) various methods used in surgical training ( 2 ) numbers and types of surgeries performed by them in the training centers ( 3 ) their plans after residency.materials and methods : a questionnaire containing 21 questions was distributed to 155 students attending an intensive 4-day teaching program . \n the questions related to orientation training , wet lab training , facilities for training , free surgical camps and detailed information about numbers and types of surgeries observed and performed . \n completed questionnaires were collected , and responses analyzed.results:one hundred and seven completed responses were analyzed . \n the majority had not received formal orientation training . \n more than half had undergone wet lab training . \n most residents performed their first ophthalmic surgery during the 1st year of residency and went to the operation theatre multiple times a week . \n most of the students planned to undergo further training after residency . \n more than half of the students found their surgical training to be fair or satisfactory.conclusions:the number and frequency of ophthalmic surgeries done by residents appear satisfactory , but further efforts from trainers on enhancing the quality and range of surgical training would benefit students and improve their satisfaction .", "id": 972} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nununited fractures of clavicle are occasionally seen in adults , but are rarely found in children . post - traumatic non - union of the clavicle is a rare complication in adulthood with a frequency of about 1% .\nthis condition is also exceptional in children , despite the frequency of clavicular fracture at any given age .\nclavicular fractures usually occur at the junction of the medial two third with the lateral one third of the bone and usually heal by conservative treatment within three weeks .\nsurgery is required in about one in 100 cases in which there is remaining deformity .\nan 8-year - old male child presented with a right - sided clavicular fracture for one year .\nthere was a history of fall while playing and the patient sustained injury to the right shoulder , which led to the fracture of the clavicle . both swelling and severe pain were present\nthe patient had received treatment from an orthopedic surgeon with a figure 8 bandage for three weeks ; however , the pain was not relieved . at one - year follow - up ,\nthe upper part of the chest , the bony prominence in the clavicular region and the overlying skin appeared normal .\nall of the arterial pulses were present in the affected limb ( i.e. , axillary , brachial and radial ) .\ndiagnosis was made following a radiograph of the right shoulder , which showed old , non - union of the clavicle at the junction of the medial two third with the outer one third .\nthe patient was treated conservatively with analgesics and shoulder exercise as the movements of the shoulder were within normal range .\nx - ray of right shoulder revealed old , non union of clavicle at the junction of medial two 3 with outer one 3 and here was roundening of both ends with no callous formation .\na 26-year - old male patient presented with a history of fracture of the right clavicle six years ago .\nhe received treatment from an orthopedic surgeon in patna with figure 8 bandages and a shoulder sling for three weeks .\nthe patient now complained of pain in the right shoulder with limitation of movement for one year . on local examination\n, there was no swelling or deformity and shoulder joint movements were within normal limits , up to 90% .\nthere had been restriction of the movements of the shoulder joint , up to 10 degrees on internal and external rotation .\na radiograph of the shoulder joint revealed an old , non - united fracture of the mid one third of the clavicle on the right side with no callus formation ( fig .\nthe patient was treated conservatively with analgesics and physiotherapy exercises . at a six - month follow - up visit ,\nx - ray revealed old non - united fracture of mid one 3 clavicle of right side and there was no callous formation .\nan 8-year - old male child presented with a right - sided clavicular fracture for one year .\nthere was a history of fall while playing and the patient sustained injury to the right shoulder , which led to the fracture of the clavicle . both swelling and severe pain were present\nthe patient had received treatment from an orthopedic surgeon with a figure 8 bandage for three weeks ; however , the pain was not relieved . at one - year follow - up ,\nthe upper part of the chest , the bony prominence in the clavicular region and the overlying skin appeared normal .\nall of the arterial pulses were present in the affected limb ( i.e. , axillary , brachial and radial ) .\ndiagnosis was made following a radiograph of the right shoulder , which showed old , non - union of the clavicle at the junction of the medial two third with the outer one third .\nthe patient was treated conservatively with analgesics and shoulder exercise as the movements of the shoulder were within normal range .\nx - ray of right shoulder revealed old , non union of clavicle at the junction of medial two 3 with outer one 3 and here was roundening of both ends with no callous formation .\na 26-year - old male patient presented with a history of fracture of the right clavicle six years ago .\nhe received treatment from an orthopedic surgeon in patna with figure 8 bandages and a shoulder sling for three weeks .\nthe patient now complained of pain in the right shoulder with limitation of movement for one year . on local examination\n, there was no swelling or deformity and shoulder joint movements were within normal limits , up to 90% .\nthere had been restriction of the movements of the shoulder joint , up to 10 degrees on internal and external rotation .\na radiograph of the shoulder joint revealed an old , non - united fracture of the mid one third of the clavicle on the right side with no callus formation ( fig .\nthe patient was treated conservatively with analgesics and physiotherapy exercises . at a six - month follow - up visit ,\nx - ray revealed old non - united fracture of mid one 3 clavicle of right side and there was no callous formation .\nan 8-year - old male child presented with a right - sided clavicular fracture for one year .\nthere was a history of fall while playing and the patient sustained injury to the right shoulder , which led to the fracture of the clavicle . both swelling and severe pain were present\nthe patient had received treatment from an orthopedic surgeon with a figure 8 bandage for three weeks ; however , the pain was not relieved . at one - year follow - up ,\nthe upper part of the chest , the bony prominence in the clavicular region and the overlying skin appeared normal .\nall of the arterial pulses were present in the affected limb ( i.e. , axillary , brachial and radial ) .\ndiagnosis was made following a radiograph of the right shoulder , which showed old , non - union of the clavicle at the junction of the medial two third with the outer one third .\nthe patient was treated conservatively with analgesics and shoulder exercise as the movements of the shoulder were within normal range .\nx - ray of right shoulder revealed old , non union of clavicle at the junction of medial two 3 with outer one 3 and here was roundening of both ends with no callous formation .\na 26-year - old male patient presented with a history of fracture of the right clavicle six years ago .\nhe received treatment from an orthopedic surgeon in patna with figure 8 bandages and a shoulder sling for three weeks .\nthe patient now complained of pain in the right shoulder with limitation of movement for one year . on local examination\n, there was no swelling or deformity and shoulder joint movements were within normal limits , up to 90% .\nthere had been restriction of the movements of the shoulder joint , up to 10 degrees on internal and external rotation .\na radiograph of the shoulder joint revealed an old , non - united fracture of the mid one third of the clavicle on the right side with no callus formation ( fig .\nthe patient was treated conservatively with analgesics and physiotherapy exercises . at a six - month follow - up visit ,\nx - ray revealed old non - united fracture of mid one 3 clavicle of right side and there was no callous formation .\nclavicular non - union is rarely asymptomatic and often results in disability from pain at the site of non - union , altered shoulder mechanics , or a compression lesion involving the underlying brachial plexus or vascular structures .\nfractures of the clavicle are usually in the medial two third of the bone , which may result from a fall and subsequent outstretched hand during the fall .\nthe lateral fragment is displaced forward and downward by the weight of the limb , while the medial fragment is held at a higher level by the sternocleidomastoid muscle .\nthe essential treatment is to support the weight of the limb by a sling tied over the opposite shoulder .\nthe fractures are almost always clinically united within three weeks . about one in 100 fractures of the clavicle require primary surgical treatment .\nsir robert peel , who established the police force of great britain , died of a fractured clavicle which ruptured the subclavian vein .\npeel was attended by sir benjamin brodie who wrote , the hemorrhage itself was the consequence of the subclavian vein having been lacerated by splinters of the fractured bone .\nif deformity persists at the bony ends of the clavicle after several months , surgical smoothening of these ends is indicated by a short incision in the line of the skin creases .\nthis causes less deformity than the scarring resulting from more extensive operative procedures that may be required for primary open reduction with internal fixation .\nin addition , major surgical procedures may carry the risk of additional surgery for non - union .\nthe non - union rate of fractures of the lateral end of the clavicle can rise to 37% when a nonsurgical treatment protocol is initially adopted . reported results for the nonsurgical treatment of fractures of the clavicle\nhave been uniformly positive ; a combined series of over 3000 fractures showed a rate of non - union of 0.4% .\noccult fracture has been well documented in the hip and the scaphoid and failure to recognize this type of fracture could lead to serious consequences . while clavicular fracture is often viewed as benign , it is important for patients to be aware that any fracture may impact expected time of recovery .\nin addition , complications such as non - union do occur and inadequate initial immobilization is a common cause .\npatients who have suffered a clavicular fracture often recover well in spite of the risk of non - union ; fatal complications that may occur following vascular injuries are extremely rare .\nfracture location and the type of immobilization have little effect on the final result or prognosis .\ncareful attention should be paid when obtaining a detailed history and physical examinations , as traumatic arthritis at either clavicular joint may mimic the symptoms of non - union .\nthe explicable evidence of osseous non - union on radiographs may be minor and may not correlate with the clinical symptoms .\na patient with an atrophic pattern of non - union may become asymptomatic with time .\nsurgeons should be cautious when operating on the non - union merely due to its presence , although asymptomatic .\nif a surgical procedure is planned , possible outcomes should be communicated to the patient , including the possibility of additional surgery , if required .", "answer": "context : fractures of the clavicle usually occur at the junction of the medial two third with the lateral one third and usually heal by nonsurgical measures . radiographs and mri of the shoulder provide helpful investigations for diagnosis and treatment . in the following cases , \n an anterior - posterior view revealed non - union of the clavicle on the right side , which is atypical in children.case report : non - union of a clavicular fracture is an extremely rare condition , especially in children . \n we are reporting two cases in this paper ; in the first case ; an 8-year - old male child visited the hospital with a history of fracture of the right clavicle one year ago . in the second case , \n a 26-year - old male patient presented with a history of fracture of the right clavicle six years ago.conclusion:careful attention should be paid when obtaining a detailed history and physical examinations , as traumatic arthritis at either clavicular joint may mimic non - union . \n the explicable evidence of osseous non - union on radiographs may be minor and may not correlate with the clinical symptoms .", "id": 973} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe compared the lumbar repositioning error ( re ) according to different lumbar angles in a \n flexion pattern ( fp ) subgroup of patients with non - specific chronic low back pain ( nsclbp ) . \n\napproximately 85% of this population was classified as having nsclbp , with no radiological \n change between the 12th rib and the inferior gluteal fold1 .\nthe management approach has been the use of subgroups classified on \n the basis of pain - provoking postures and movements in nsclbp2 .\nrepositioning error ( re ) is defined as proprioceptive impairment , \n known to result in poor spinal stability3 . \n\nimpaired proprioception in positions such as sitting and standing can be related to lbp . in \n particular , it is associated with flexion direction in the subgroup with pain provoked by \n lumbar flexion4 . however , few studies have \n examined re in subjects with flexion - related lbp during the performance of different lumbar \n flexion angles , as in extension on sitting and standing upright postures .\nthus , the purpose \n of this study was to compare changes in lumbar re at different angles while standing and \n re - standing and sitting and re - sitting in a subgroup of fp subjects with nsclbp .\ns system5 , \n 6 and was defined as subjects with pain \n provoked by postures and movement - related flexion of the lumbar spine . in the fp subgroup\n, \n symptoms were relieved by movement associated with extension , lordosis of lumbar segments , \n and the loss of a neutral spine posture due to a flexed spine5 , 6 .\nthe subjects were aged \n 44.78.2 years ( mean sd ) with a height of 165.45.1 cm , a body weight of 62.37.2 kg , a \n korean oswestry disability index ( odi ) of 30.04.0% , and a visual analog scale ( vas ) score \n of 5.51.2 .\nethical approval was obtained from the inje university faculty of health science \n human ethics committee .\nwe used a dual inclinometer ( acumar , lafayette instrument co. , \n lafayette , usa ) to measure the lumbar re at the main and companion parts ( l1 and sacrum ) . \n\nintra - test reliability of the dual inclinometer was 0.90 , and the inter - test reliability was \n 0.85 .\nthe subjects were required to stand upright for 5 s and to hold lumbar flexion angles \n of 30 and 15 and a lumbar extension angle of 15 for 5 s , followed by return to the \n starting position .\nthe re of the lumbar spine was defined \n as the difference in the mean sagittal angles between neutral sitting and re - sitting phases \n and between the standing and re - standing phases of the task . the spss software ( ver .\n12.0 ; \n spss , chicago , il , usa ) was used for all analyses , and the level of statistical significance \n was set at 0.05 .\none - way repeated - measures analysis of variance and the least significant \n difference ( lsd ) test as a post hoc pair - wise comparison were used to \n determine significant re differences among the six tasks .\nthe lumbar re increased significantly with flexion at 30 during sitting . upon sitting \n upright , the lumbar re between sitting and re - sitting was significantly greater with a \n flexion of 30 ( 5.13.7 ) than 15 ( 2.03.7 ) or with an extension of 15 ( 1.51.9 ) ( p < \n 0.05 ) .\nin addition , re while sitting with a flexion of 30 was significantly greater than \n that between the standing and re - standing positions during flexions of 30 ( 1.91.5 ) and \n 15 ( 0.70.6 ) and an extension of 15 ( 0.80.6 ) ( p < 0.05 ) . upon standing upright ,\nthe \n lumbar re between the standing and re - standing positions during a flexion of 30 was \n significantly greater than during a flexion of 15 or extension of 15 ( p < 0.05 ) .\nin our study , lumbar spine re increased in a specific direction while in the sitting \n position in the fp subgroup . in accordance with previous research5 , 6 ,\nthe fp subgroup in \n this study had a deficit in flexed - toward status while sitting , but this was not apparent \n while standing . however , while the previous study used lumbar full flexion in the standing \n position , our study used a flexion angle of 30. the neutral re from 30 of flexion was \n greater than those from 15 of flexion or 15 of extension while standing , and less than \n that from 30 of flexion while sitting .\nthe standing position would have added \n proprioceptive input from other distant receptors , while the adoption of a seated position \n would minimize other proprioceptive inputs by immobilizing the lower legs and the \n pelvis7 , 8 .\nfurthermore , this may be due to characteristics of the fp group , \n where pain is provoked during sitting , whereas the pain tended to be relieved upon \n standing2 .\nthe results of this study \n revealed the highest displacement changes between sitting and re - sitting on flexion of 30 \n of the lumbar spine from the upright sitting posture . when spinal structures , such as \n passive ligaments or active muscles are stretched or flexed during sitting , reflexive muscle \n activity may be reduced , passive structures may be lengthened , and their tension may be \n reduced due to unsuitable stretching stimulation from the central nervous system9 . dolan and green10 reported significantly increased lumbar re following 5 min \n in a slouched posture , but not following a 3-s duration .\nour study showed increased re \n immediately while sitting at a flexion angle of 30. we suggest that a higher lumbar flexion \n angle may have a negative impact on lumbar positioning sense while in the sitting posture \n than in the standing posture in fp subjects with nslbp .\nwe also suggest that the measurement \n method for lumbar res would be more effective while sitting using a flexion angle of 30 in \n fp subjects .", "answer": "[ purpose ] this study determined the change in lumbar position sense according to lumbar \n angles in a flexion pattern ( fp ) subgroup of patients with non - specific chronic low back \n pain ( ncslbp ) . [ subjects ] thirteen subjects with fp low back pain participated . \n [ methods ] \n the lumbar repositioning error ( re ) of subjects was measured between a neutral starting \n position and re - position phases at three angles , in sitting and standing upright \n positions . \n [ results ] lumbar re was significantly greater during lumbar flexion at a 30 \n angle in the sitting position than in the other tasks . \n [ conclusion ] in the flexion - related \n subgroup , the lumbar re measurement may be a more sensitive evaluation method using a \n lumbar flexion angle of 30 while in the sitting position , compared with other angles in \n sitting or standing positions .", "id": 974} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe scope of newborn screening has expanded greatly in the 52 years since robert guthrie published his microbial assay for phenylalanine and the use of dried blood spots in screening for phenylketonuria .\nthough guthrie and others went on to develop blood - spot screening methods for further disorders none were taken up very widely until the development of immunoassays and the ability to screen for congenital hypothyroidism , now the most widely practiced screen worldwide .\nimmunoassay - based screens for other disorders followed , cystic fibrosis and congenital adrenal hyperplasia in particular , but none have achieved general acceptance .\nmore recently , tandem - mass - spectrometry ( ms - ms ) , with its ability to measure a wide range of metabolites simultaneously , has opened up a further range of disorders , many of which are very rare but can be incorporated with screening for phenylketonuria at little additional cost .\nthus , in large parts of the usa screening covers over 50 conditions ( 1 ) though this total is inflated counting sickle - associated haemoglobin variants as separate diseases .\neuropean countries with equally well - developed medical systems have very different screening policies : in 2009 , the maximum number of conditions covered was 30 and some countries were screening for four or less ( 2 ) .\nthere was little consensus regarding information provision , informed consent , storage and disposal of residual specimens , screening technologies and disease definition .\nthe reasons for these differences are not always obvious though clearly funding issues and the availability of an adequate clinical infrastructure must play a part .\nall formal policy reviews have acknowledged the ten principles enunciated by wilson and jungner in 1968 ( 3 ) . these are couched largely in qualitative terms\n, there should be a suitable test which should be acceptable to the population and there should be an accepted treatment .\nnevertheless , the uk national screening committee has until very recently emphasized the importance of having firm numerical data and evidence from a high - quality randomized controlled trial before accepting a new condition ( 4 ) .\nhowever , it is recognized that for clinically heterogeneous and relatively rare disorders , such as those now readily accessible through ms - ms screening , a degree of compromise is required .\nmedium - chain acyl - coa dehydrogenase deficiency was accepted on the basis of a large - scale pilot study ( 5 ) and preliminary studies on five additional disorders detectable by ms - ms are underway .\nthe approach in the usa has been quite different , with federal policy based largely on the results of a survey carried out by the american college of medical genetics ( 6 ) .\nthis canvassed opinions ( rather than data ) from a wide range of professional and lay personnel in the usa and abroad and commissioned literature reviews on specific diseases from practicing academic clinicians .\nthis resulted in the identification of 29 conditions for which screening should be mandated and an additional 25 conditions that would be identified as part of differential diagnosis .\nthe work was subsequently taken forward and amplified by the secretary s advisory committee on hereditary disorders in infants and children ( 7 ) , forming the basis for both federal and state legislation .\nscreening policy is ultimately decided at state level and based on explicit legislation , with significant regional variations in both the number of disorders covered ( 1 ) and practices such as how long the blood collecting cards are retained after screening has finished ( 8) . this overt political dimension leaves policy - makers exposed to pressure from groups such as the save babies through screening foundation and there is almost a degree of competition as to which state screens for the most disorders . in countries like the uk where screening is offered as part of the national health service with no direct legislative basis policy tends to attract less public attention though nevertheless the uk screening programmes for cystic fibrosis and sickle cell diseases were introduced following direct pressure at the political level rather than through the formal advisory channels .\nthe wilson and jungner analysis was based mainly on adult disease and largely neglected the family dimension of newborn screening : the value of genetic information and the way that prompt diagnosis , even of an incurable condition , can ease the family journey .\nfamily impact is the main rationale behind the welsh screening programme for duchenne muscular dystrophy which has been well - accepted locally but requires considerable professional input and is not supported in the rest of the uk .\ncystic fibrosis is an obvious example as in the absence of screening diagnosis is often considerably delayed , leading to significantly worse outcomes .\ndiagnostic odyssey and has no warning of the possibility of future children also being affected .\nattitudes of at - risk couples towards antenatal diagnosis of cystic fibrosis are ambivalent ( 9 ) but overall the introduction of newborn screening has resulted in a significant decrease in the number of babies born with the condition ( 10 ) .\neven before antenatal diagnosis became possible families with a phenylketonuric child diagnosed by screening tended to limit family size subsequently ( 11 ) .\nhowever , in general policy - makers focus their attention on the value of newborn screening to the baby concerned and have mixed views about wider genetic implications .\ngenetic exceptionalism is the view , strongly held by some civil liberties groups , that genetic information is special and must be treated differently from other types of medical information .\ndna analysis may reveal carrier status in individuals with no family history of the disorder concerned and in some countries is prohibited without a specific request from a registered medical practitioner .\nsuch sensitivities are reflected in some of the screening protocols , particularly those for cystic fibrosis .\nseveral screening programmes have retained the original two - step irt approach and require a second blood sample despite the convenience and greater specificity of analysing the cftr gene on the initial sample .\nprogrammes that do use dna analysis vary greatly in the mutation panel used : some restricting it to a few relatively common mutations associated with severe disease , others using a much broader panel with a corresponding increase in the number of unaffected carriers found .\nother programmes include a pap ( pancreatitis associated protein ) step in an attempt to maintain specificity but minimise or avoid carrier detection ( 12 , 13 ) . the uk protocol attempts to minimise carrier detection but by different means ( figure 1 , panel a ) while also recognising that a mutation panel optimised for northern european populations has inherent disadvantages for those of other geographical origin ( panel b ) .\ncomplicated protocols of this type place a considerable administrative burden on the laboratory . travelling in the opposite direction , studies of the potential of exome sequencing as a first - line method of newborn screening and the possibility that genomic data be made available as a resource for parents and doctors throughout infancy and childhood to inform health care\nthere is usually less anxiety about genetic information obtained at the protein level even though , with haemoglobin variants for example , this may inform directly on the underlying dna sequence .\nindeed , when a baby has received a blood transfusion prior to the screening sample being taken some programmes use dna analysis rather than waiting several weeks for the infused erythrocytes to be removed .\nnewborn screening for sickle cell diseases and related haemoglobin abnormalities detects a significant number of carriers : 1 baby in 71 born in england in 201112 .\nthere are different views on whether this is desirable despite the presence of an antenatal screening programme and , as far as possible , linkage between the two programmes .\nms - ms methods capable of detecting individual haemoglobin variants without the corresponding carriers have been developed ( 15 ) and it remains to be seen whether this will affect practice .\nwith improvements in analytical performance the definition of normal has tended to be drawn ever more tightly . however , the primary purpose of screening is prevention or amelioration of disease rather than the detection of a biochemical / genetic abnormality as such .\nthus , not all children with a persistently increased blood phenylalanine concentration will become mentally impaired : there is fairly good evidence for a threshold of about 600\nthis threshold has been adopted in france and germany but is ignored in many other countries .\nsimilarly with congenital hypothyroidism , improvements in assay sensitivity have resulted in many screening centres adopting lower cut - offs and consequently finding an increased number of cases .\nhowever , their gender distribution is markedly different from that in cases diagnosed clinically prior to the start of screening and there is no firm evidence that most of these additional cases benefit from their treatment . the biological level ( gene , protein\n, enzymic activity , metabolic pathway , individual metabolite ) at which screening and confirmatory investigations are performed also has an important impact on disease definition .\nthus , medium - chain acyl - coa dehydrogenase deficiency ( mcadd ) is readily detectable by increased blood - spot octanoylcarnitine on ms - ms screening . in the netherlands enzyme assay using phenylpropionyl - coa is regarded as the gold - standard confirmatory test .\nthe current uk screening protocol defines mcadd in terms of having two mutations in the mcad ( acadm ) gene and genotyping is central to the clinical follow - up protocol .\nhowever , data from the pilot study ( 5 ) show that all babies except one with genotypes that have previously been reported from clinically - presenting cases showed urinary hexanoylglycine > 5 micromol / mol creatinine on immediate follow - up .\nthis would appear to be a more effective indicator of the risk of metabolic decompensation ( which is what we are really wishing to screen for ) than mutation analysis and avoids the complication of inadvertent carrier detection .\nviewed in the context of everything else that can go wrong in pregnancy , childbirth and afterwards , newborn screening seems a fairly insignificant thing to worry about but the importance of having suitable information available if required is universally recognized . the way that this is provided and the amount of detail given vary considerably .\nthe uk national screening committee requires that evidence - based information , explaining the consequences of testing , investigation and treatment , should be made available to potential participants to assist them in making an informed choice .\nthe emphasis on choice is in keeping with current political philosophy but it could be argued that if parents were truly informed then choosing to have their baby screened would be automatic .\neven carefully worded information can leave room for misunderstanding : we read the form and our understanding was that the conditions were hereditary .\nwe did nt want to cause baby the pain of having a needle in her heel .\ncome on then let s get on with it. we both looked at each other and were afraid to say anything so the baby screamed and we felt bad for doing it .\nshe saved our daughter ( with phenylketonuria ) to grow up a lovely healthy bright little girl ( 17 ) .\nshould we really be presenting screening as an option which rational parents might like to consider ?\n. in some us states screening is compulsory , required by law , so that ( in theory at least ) every baby gets screened .\nthe supreme court of ireland upheld the right of parents who already had a child with phenylketonuria not to have their newborn baby screened ( 18 ) .\nthe united nations convention on the rights of the child states that the best interests of the child must be a top priority in all actions .\nhowever , whether screening is truly in the interests of the affected child is sometimes debatable , particularly for disorders where treatment is invasive and the effect is to slow the progression of a debilitating disease rather than prevent it .\nmost disorders show some degree of heterogeneity and this may make a clear answer impossible : for example , severe propionic acidaemia is almost untreatable , with an inexorable deterioration , but patients with milder variants can survive and go on to lead virtually normal lives if diagnosed and treated early .\nthe current diversity of national policies relating to newborn screening reflects both practical limitations in health care organization and funding and widely different philosophical approaches to a variety of highly emotive issues .\ndecisions will become more difficult still as screening technology advances , with the use of orbitrap mass spectrometry for example , and the number and variety of disorders readily accessible increases still further .", "answer": "summarynewborn blood - spot screening to detect potentially treatable disorders is widely practiced across the globe . however , there are great variations in practice , both in terms of disorders covered , screening technologies , disease definition , information provision , parental informed consent , and storage and disposal of residual specimens , partly reflecting the degree to which screening is the subject of explicit legislation ( and thus public and media pressure ) or is embedded in a general health care system and managed at an executive level . \n it is generally accepted that disorders to be screened for should comply with the ten wilson and jungner criteria , but the way that compliance is assessed ranges from broadly - based opinion surveys to detailed analysis of quantitative data . \n consequently , even countries with comparable levels of economic development and health care show large differences in the number of disorders screened for . \n there are several areas on which there are no generally accepted guidelines : how should parents be informed about screening and to what extent should they be encouraged to regard screening as an option to choose to refuse ? \n is dna mutation analysis acceptable as part of a screening protocol ? \n how soon should the blood samples be destroyed once screening has been completed ? \n as technology advances and the potential scope of screening expands at both the metabolite and genome level , challenging policy issues will have to be faced .", "id": 975} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe term fibromatosis refers to a group of benign soft tissue tumors ( fibromas ) , which have certain characteristics in common , including absence of cytologic and clinical features of malignancy , a histology consistent with proliferation of well - differentiated fibroblasts , an infiltrative growth pattern , and aggressive clinical behavior with frequent local recurrence .\nherein we report this unusual presentation of benign fibromatosis over the dorsum of both feet .\na 40-year - old female patient presented with multiple raised growths over both feet since four years .\ncontractures , bony deformities and keloids were absent . on examination , symmetrical , well - defined\n, firm nodules coalescing to form lobulated plaques were noted over the dorsum of both feet extending from base of the 2 , 3 , 4 , and 5 toes to the mid - foot [ figures 1 and 2 ] .\nradiographs of both feet showed no bony deformity and ultrasound of both feet showed no significant soft tissue thickening .\nan elliptical biopsy of lesion taken for histopathology showed epidermis with hyperkeratosis , acanthosis , mild parakeratosis and prominent granular layer .\nsuperficial dermis was unremarkable and deep dermis showed fibroblastic proliferation with variable vascularity and lack of inflammatory infiltrate , and thick bundles of irregular collagen characteristic of fibromatosis [ figures 3 and 4 ] . with these clinical and histopathological features ,\nthe patient was advised topical keratolytics along with intralesional steroids for 2 months with minimal response .\nthe patient was counseled about the benign nature of the disease and measures for lifestyle modification and proper footwear .\nmultiple well - defined firm nodules coalescing to form lobulated plaques distributed in a symmetrical pattern over dorsum of both feet , extending from base of the 2 , 3 , 4 , and 5 toes to the the mid - foot close - up view of the lesion showing diffuse lobulated plaque over the dorsum of left foot epidermis showing hyperkeratosis and acanthosis with deep dermis showing fibroblastic proliferation with thick bundles of irregular collagen ( hematoxylin and eosin 4 ) epidermis showing hyperkeratosis , acanthosis , mild parakeratosis , and a prominent granular layer .\nsuperficial dermis was unremarkable and deep dermis showed fibroblastic proliferation with variable vascularity and lack of an inflammatory infiltrate , with thick bundles of irregular collagen ( hematoxylin and eosin 40 )\nthe musculoskeletal fibromatosis represent a wide range of fibroblastic to myofibroblastic proliferations that are grouped together because of their similar pathologic appearances .\nthe clinical behavior of these tumors is intermediate between that of benign and malignant fibrous lesions ; they commonly manifest infiltrative growth , resulting in frequent local recurrence , but lacking metastatic potential . the world health organization committee for classification of soft tissue tumors in 2002 categorized these lesions as superficial or deep based on their anatomic location . superficial fibromatosis ( palmar , plantar , penile , and knuckle pads ) and deep fibromatosis ( nonmetastasizing fibrosarcoma , and desmoids tumor ) , which are rapidly growing tumors involving the muscular structures or aponeuroses . clinically , it may present as solitary or multiple lesions affecting one or many sites ; the prevalence of palmoplantar involvement may vary 0 - 28 percent of cases .\nthe superficial fibromatosis , whether they occur in adults ( palmar and plantar ) or children ( calcifying aponeurotic fibroma , lipofibromatosis , and inclusion body fibromatosis ) , are typically small lesions that grow slowly .\nthe deep fibromatosis in both adults ( desmoid type and abdominal wall ) and children ( fibromatosis colli and myofibroma and myofibromatosis ) are usually larger and often enlarge more rapidly .\nthe diagnosis of deep fibromatosis may be suggested by their clinical characteristics , particularly anatomic location and patient age : fibromatosis colli that typically involves the lower neck and sternocleidomastoid muscle in a young child ; abdominal wall fibromatosis that manifests as a mass involving the rectus abdominus muscle and is often related to pregnancy ; or myofibromatosis that occurs as multicentric disease in a young child ; palmar fibromatosis , a fibromatous hyperplasia of the palmar aponeurosis characterized by nodular thickening of the fascia associated with flexion contractures of one or more digits ; plantar fibromatosis comprising single or multiple painful nodules over the medial half of mid - foot with a tendency to ulcerate that may be locally invasive and can recur ; penile fibromatosis , characterized by one or more dense fibrous plaques on the penile shaft that occur as an isolated abnormality or as part of polyfibromatosis ; knuckle pads , characterized by circumscribed thickening overlying the proximal interphalangeal joint ; desmoid tumors - histologically benign but locally aggressive fibrous neoplasms originating from the musculoaponeurotic structures with often nonspecific findings .\ndiagnosis relies on histopathologic findings characterised by multinodular cellular proliferations of uniform , plump , spindle shaped fibroblastic cells within a collagenous stroma .\nlongstanding lesions are less cellular and contain increased amounts of dense collagen , suggestive of fibromatosis .\ncross - sectional imaging ( ultrasonography , computed tomography , or magnetic resonance imaging [ mri ] ) reveals lesion location , extent , and involvement of adjacent structures and thus is useful for tumor staging and evaluation of local recurrences .\nadditional mri features that are related to underlying pathologic characteristics provide increased specificity for the diagnosis of musculoskeletal fibromatosis .\ntreatment of musculoskeletal fibromatosis may range from conservative management to surgical resection and is influenced by the specific diagnosis and extent of the lesion determined at imaging evaluation .\nlocal recurrence is common after surgical resection , owing to the infiltrative growth seen pathologically in these lesions .\nwide excision of fascia is the treatment of choice for solitary painful lesions or lesions causing flexion contractures .\nrecurrences are common in aggressive fibromatosis , but not so in superficial benign fibromatosis . in a case series of 14 patients with plantar fibromatosis , it was noted that symptoms improve with time with conservative management and intralesional corticosteroids may not always cause subsidence of symptoms . among the nonsurgical treatments , radiation therapy , vitamin e , local injection of calcium channel blockers , interferon , corticosteroids or collagenase , and colchicine\n, we used intralesional injection of triamcinolone in escalating dose of 10 and 40 mg / ml every three weeks along with topical salicylic acid 12% and urea for local application twice daily that showed minimal response .\nthis case report presents the benign nature of the condition , its relative resistance to treatment and an uncommon symmetrical presentation of fibromatosis over the dorsum of both feet .", "answer": "fibromatosis is benign fibrous tissue condition intermediate between benign fibroma and metastasizing fibrosarcoma . \n the lesion tends to infiltrate and recur when removed , but do not metastasize . \n the lesion may be single or multiple , and the likelihood of recurrence after surgical removal varies with location of the lesion and age . a 40-year - old female presented with multiple raised lesions over both feet since 4 years , they were multiple well - defined firm nodules coalescing to form lobulated plaques distributed in a symmetrical pattern over the dorsum of both feet . \n histopathology of skin showed epidermis with hyperkeratosis , acanthosis , mild parakeratosis , and prominent granular layer . \n superficial dermis was unremarkable and deep dermis showed thick bundles of irregular collagen and fibroblastic proliferation , suggestive of fibromatosis . \n this case is being reported for its unusual presentation of fibromatosis over the dorsum of both feet .", "id": 976} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe term nonconvulsive status epilepticus ( ncse ) is defined as a range of conditions in which electrographic seizure activity is prolonged and results in nonconvulsive clinical symptoms , .\nthe clinical features of ncse may be subtle and diverse , and confirmation relies on the electroencephalogram ( eeg ) .\nseveral approaches to establishing criteria for ncse in adults have been published ( table 1 ) , , , and some clinical states may lie along an ictal interictal continuum .\nperiodic discharges are often regarded on the interictal end of the spectrum , but when accompanied by clinical features including impaired vigilance and when signs resolve proximate to treatment , then this lends evidence to the ictal nature of periodic discharges along this spectrum .\nperiodic lateralized epileptiform discharges ( pleds ) , in particular , have sparked controversy with regard to being part of the ictal vs. interictal spectrum .\nperiodic lateralized epileptiform discharges can occur in the temporal vicinity of an overt seizure , thus reflecting an ictal \ninterictal continuum phenomenon that can continue for weeks ( chronic pleds ) in conscious patients with retained alpha or basic rhythm .\nhowever , when they occur in a patient with altered level of consciousness , some authors regard it as ictal , , , , , , , , . since changes in mental status are common in epileptic encephalopathies and developmental delay such as in patients with cerebral palsy , it can be difficult or impossible to determine whether they are in status epilepticus , unless there is a discernible clinical improvement with treatment .\nwe report the case of a patient with chronic epilepsy and cerebral palsy ( cp ) who presented with deterioration from an already impaired baseline .\nalthough the eeg revealed slow pleds which are not typical of ncse , the patient showed a good clinical and eeg response to benzodiazepines with pled regression .\nthis 49-year - old man with cerebral palsy , mental retardation , and epilepsy residing in a long - term care facility for the prior 13 years had been awake , noncommunicative , but responsive to auditory and visual stimuli .\nhe was treated with phenytoin and levetiracetam and had yearly breakthrough seizures over the prior 10 years .\nhe had recently developed fever and dyspnea with a drop in oxygen saturation and was suspected of having aspiration pneumonia complicated by sepsis .\nhe was given intravenous antibiotics , fluids , and supplemental oxygen and was transferred to our facility . following a mild generalized tonic \nclonic seizure , his examination remained persistently unchanged but he was now unresponsive to auditory , visual , and noxious stimuli , with a fluctuating level of alertness .\nplasma phenytoin level was low at 34.8 mol / l ( normal : 4080 mol / l ) .\n1 ) showed intrusions of excess slow left - sided periodic lateralized epileptiform discharges ( pleds ) on a background of normal alpha pattern .\nadministration of 1 mg of iv lorazepam resulted in resolution of the slow pleds ( fig . 2 ) and\nimprovement in the patient 's neurological status , which now became responsive to auditory , noxious , and visual stimuli that occurred in a matter of 15 min after administration of lorazepam . by the next morning , his condition had greatly improved and he was near his baseline status .\nhe received additional intravenous loading doses of phenytoin and levetiracetam on the same day , and his maintenance doses were adjusted .\nbrain ct showed a large central meningioma as well as a small posterior fossa meningioma ( fig . \nreview of his old brain ct films ( done seven years ago ) showed no such lesions .\nbecause of his poor quality of life and the risks involved , neurosurgery was not considered an option , and the patient was managed medically with antiepileptic medication .\n4 ) , and the patient was discharged to a long - term care facility for further care .\nthis patient with chronic epilepsy and cerebral palsy ( cp ) showed deterioration from a baseline that was already impaired , a finding described in ncse in those with developmental disability , .\nthe eeg findings were not typical of ncse in that slow pleds lie in the gray zone along the ictal interictal continuum .\ncerebral palsy is a complex , heterogeneous lifelong condition with significant disability and long - term challenges that persist into adult life .\nepilepsy is reported in 35% to over 60% of patients with cp , and is more frequent in patients with more severe disability\n. sixteen percent of children with cp and epilepsy may develop nonconvulsive and/or convulsive status epilepticus .\nbrain tumors , particularly primary ones , are associated more frequently with both convulsive and nonconvulsive status epilepticus , .\nelectroencephalographic changes in mass lesions reflect irritability around the penumbra of the lesion , in this case , on the left .\none can speculate that the focal structural lesion in the setting of chronic diffuse brain dysfunction , along with intercurrent infection and low aed levels , represented the multiple risk factors seen in the recurrence of seizures and appearance of ncse , . periodic lateralized epileptiform discharges ( fig . \n1 ) consist of periodic spike - and - slow wave or sharp - and - slow wave complexes , typically with a frequency of 12 hz . in our patient , the frequency was ~ 0.5 hz .\nperiodic lateralized epileptiform discharges occur in a variety of conditions such as strokes , tumors , and infections ; these together comprise around 50% of the underlying etiologies .\nslow growing extraaxial tumors such as meningiomas usually produce little eeg disturbance unless they compress and displace brain tissue or cause hydrocephalus such as in our case .\nperiodic lateralized epileptiform discharges are reported to support a diagnosis of ncse if they meet certain conditions , in particular , good proximate clinical and eeg response to benzodiazepines with pled regression ( table 1 ) .\nwhen eeg and clinical regression are not clear , spect or pet scanning can guide the clinician in the possible ictal ( versus interictal ) nature of the periodic discharges , .\nthere are diagnostic and management challenges in patients with long - term disability whose cognitive and neurological baselines are impaired and not always known to the clinical caregivers .\nadditionally , a diagnosis of ncse may be difficult to make when this baseline is unknown and when the eeg findings represent a pattern that lies along the ictal interictal continuum .\nelectroencephalogram can establish where along this continuum the patient resides , following which treatment that balances the risk benefit needs of the patient , and the needs of chronic caregivers , can then be provided and monitored so as to offer the patient the optimal chance for regaining lost function with minimal risk .", "answer": "the presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus . \n nonconvulsive status epilepticus ( ncse ) needs electroencephalographic ( eeg ) monitoring to be confirmed as it may be clinically subtle . \n furthermore , it may present with a variety of ictal eeg morphologies . \n we report a case of a patient with cerebral palsy and a large central meningioma . \n electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges ( pleds ) ( a pattern considered as being situated in the ictal \n interictal continuum ) on an alpha background . \n the patient was treated for ncse successfully with benzodiazepines followed by up - titration of his antiepileptic drug doses .", "id": 977} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncardiovascular disease is the most common cause of mortality in dialysis patients that is responsible for about 60% of their mortality and is also 30 times more common than in general population .\ndifferent cardiovascular disorders , such as left ventricular hypertrophy ( lvh ) , coronary artery diseases , congestive heart failure ( chf ) , and arterial hypertension are commonly seen in these patients .\nin addition , calcification of cardiac valves are common and may cause valvular and annular thickening that in turn could lead to valvular stenosis or regurgitation .\nsome predisposing factors of cardiac disorders in dialysis patients are secondary hyperparathyroidism , long term hypertension , and anemia .\ndifferent electrocardiographic abnormality may be seen in dialysis patients , such as st , t change , ventricular and supra - ventricular arrhythmia and qt interval prolongation . in the electrocardiogram ,\nqt interval is the time between the start of the q wave and the end of the t wave .\nwhen heart rate increased then qt interval was decreased , so qt interval could be corrected with heart rate .\nthere are a number of different correction formulas , but the standard clinical correction is to use bazett 's formula ( qt/r - r , where r - r is the rr interval in seconds ) .\nthe normal corrected qt ( qtc ) interval for males and females are 430 ms and 450 ms , respectively .\nthe borderline qtc for a male is 431 - 450 and borderline qtc for a female is 451 - 470 and the abnormal qtc range for a male is > 450 and for a female is > 470 .\nthe qtc interval could be prolonged due to electrolyte abnormalities ( hypomagnesaemia and hypokalemia ) , drug consumption ( antihistaminic , antiarrhythmic , and antibiotics ) , brain trauma and genetic abnormalities ( long qt syndrome ) .\npatients with chronic renal failure and dialysis patients had a greater qtc interval and qt dispersion ( qtd ) ( qtd = qtmax qtmin ) compared with the normal population . a single session of hd could be increased qtc in patients undergoing hd .\nmoreover , qt interval may be a predictor of ventricular arrhythmia and cardiovascular mortality in chronic kidney disease and dialysis patients .\nalthough there are some studies about qtc and qtc dispersion in hemodialysis ( hd ) patients with different results ; however , there are only a few studies concerning relationship of qtc internal and qtd with echocardiography findings , so the aim of this study was the evaluation of these relationship in dialysis patients .\nin a cross - sectional study , 60 hd patients with age > 18 years and the dialysis duration > 3 months were enrolled .\nexclusion criteria were : antiarrhythmic drugs consumption , history of cardiac diseases such as arrhythmia , heart block or chf . before dialysis session , electrocardiography ( ecg ) and echocardiography\nalso , qtd was measured by mentioned formula ( qtd = qtmax qtmin ) in 12 leads ecg .\nthe patients were on hd , by fresenius digital machine ( 4008b , germany ) and gambro digital machine ( ak95 and ak96 , sweden ) , 2 - 3 times / week , as a regular method ( 4 - 4.5 h with blood flow of 250 - 350 ml / min , dialysate flow of 500 ml / min and ultra - filtration based on the patient 's condition ) .\nthe used buffer was bicarbonate powder , and the type of filters were intermediate and high efficient polysulfone membrane ( r5 , r6 ) made by soha factory under license of fresenius company .\nserum creatinine , hemoglobin , ca , parathyroid hormone ( pth ) , na , k , hco3 , and ph were checked by ra1000 machine ( made in italy ) .\nall laboratory tests were done before the dialysis session and were checked in a single laboratory .\nechocardiography and ecg were done before the dialysis session and by single cardiologist and technician respectively .\nall data and information were confidential , and for ecg and echocardiography taking an informed consent was taken from each patient . in echocardiography , left ventricular ejection fraction ( lvef ) , lvh , pulmonary artery pressure ( pap ) and valvular disorders were evaluated .\nat the end of the study , data were analyzed using spss software ( version 19 , ibm corporation ) .\npearson correlation coefficient , two - independent samples t - test and anova were used for statistical analysis .\nthis study was approved by ethical committee of shahrekord university of medical sciences with the grant number of 904 .\nmean body mass indexes ( bmis ) ( post dialysis ) and duration of dialysis were 21.77 3.6\nmean qtc interval of the patients was 0.441 0.056 s ; however , qtc interval in men and women were 0.43 0.04 s and 0.45 0.07 s , respectively ( p > 0.05 ) .\nqtd in all of the patients was 64.17 25.93 ms , however in men and women were 62.70 28.05 ms and 66.52 22.48 ms respectively ( p = 0.87 ) .\nmean urea reduction ratio in men and women were 68.14% 9.34% and 68.22% 3.88% ; however , kt / v was 1.45 0.17 and 1.49 0.16 among men and women , respectively . characteristics of patients and their association with qtc and qtd sd = standard deviation , bmi = body mass index , pth = parathyroid hormone , qtc = corrected qt , qtd = qt dispersion there was no statistically significant relationship between qtc interval or qtd with duration of dialysis , bmi , age , and gender ( p > 0.05 ) .\nin ecg , lvh was seen in 23 ( 38.3% ) patients and st change in 14 patients ( 23.3% ) . in echocardiography ,\nmitral regurgitation ( mr ) , tricuspid regurgitation ( tr ) , and aortic insufficiency ( ai ) were found in 54 , 47 , and 11 patients respectively [ table 2 ] .\nin addition , no significant relation was found between qtc interval and qtd with mr , tr , ai , lvh , septal thickness ( st ) and pap [ table 3 ] . qtc interval and qtd has also no correlation with serum pth or ca , k or hco3 .\nseverity of valvular disorders in the patients mr = mitral regurgitation , tr = tricuspid regurgitation , ai = aortic insufficiency echocardiographic findings and their association with qtc and qtd qtc = corrected qt , qtd = qt dispersion , pap = pulmonary artery pressure , lvef = left ventricular ejection fraction , lvh = left ventricular hypertrophy , mr = mitral regurgitation , tr = tricuspid regurgitation , ai = aortic insufficiency , pe = pericardial effusion\nour findings revealed that , in hd patients , qtc interval and qtd had not any correlation with valvular disorders ( mr , ai , and tr ) , lvh or other echocardiographic findings such as pap and st .\nfurthermore , there was no relationship between qtc interval and qtd with serum ca , k , hco3 , pth . in hd patients , cardiac abnormalities such as vascular calcification\nare common and are associated with the development of lvh , that may cause increased cardiac arrhythmias and mortality .\nelevation of calcium - phosphorus product can also cause valvular calcification and stenosis in these patients .\nmitral and aortic calcification and stenosis are common in these patients ; however , tricuspid and pulmonic valve calcification is rare .\nqtc interval prolongation in chronic kidney disease and hd patients was shown in some studies such as covic et al . and ljutic et al .\nstudies which postdialysis qtc interval was 434 29 ms and 445.7 36.9 ms respectively , while in our patients qtc interval was 444.6 54.5 ms . selby and mcintyre in a review article reported that hd can increase qtc interval and qtd and is also capable of inducing arrhythmias and increasing mortality especially in patients with ischemic heart disease . in nakamura\nstudy on 48 dialysis patients , throughout the follow - up period , there was a higher incidence of cardiovascular death in patients with prolongation of qtc dispersion after hd .\nshowed that the serum potassium was significantly higher in hd patients when compared to continuous ambulatory peritoneal dialysis ( capd ) patients and rate of qt interval dispersions was significantly higher in hd and capd patients when compared with healthy controls .\nthey concluded that there is a tendency to cardiac arrhythmias in hd patients during the postdialysis period .\nmaule et al . showed that after the hd session , qtc increased in 56% and decreased in 43% of the patients\nafter dialysis session , cell - associated mg levels and qtd increased significantly in averbukh et al .\nstudy , so he concluded that excess daily mg intake and increased concentrations of cell - associated mg could be responsible for qtc prolongation in these patients .\nchange in serum electrolytes during hd may also be responsible at least partially , to increase qtc or qtd .\nfor example , increase of qtc interval after a dialysis session , and its correlation with plasma calcium level , postdialysis blood pressure , lvef and st was shown in covic et al .\nshowed that qtd increased during hd due to serum k depletion and then return to baseline 2 h after the end of dialysis .\nqt prolongation during dialysis may also predispose to arrhythmia especially in the cardiac disease patients , nppi et al . demonstrated that hd increases qtd if a low - calcium dialysate is used . therefore\n, use of a low - calcium dialysate may predispose hd patients to ventricular arrhythmias .\n16 hd patients showed that qtc interval has a reverse correlation with k and ca concentrations of dialysate .\nhowever , in hd children , ozdemir et al . found that qtc interval has no correlation with the patients sex , age and presence of hypertension or lvh but patients with left ventricular systolic dysfunction had significantly greater qtc dispersion .\nsimilar to our study , the changes in serum ca or k of the patients during dialysis were not associated with the qtc interval in this study . moreover , in hekmat et al.s study on 49 hd patients , qtc interval had not correlation with serum electrolytes and blood gas findings . in voiculescu\nstudy , there was no statistically significant correlation between qt interval and serum concentrations of mg , po4 in hd patients too .\nin addition , qtc interval was not dependent from lvef , arrhythmias or sudden death .\nour results had some similarities with some of above - mentioned studies as well as some differences with the others .\nthe observed controversy between our study and some of these studies might be due to the discrepancy in the number of cases or racial differences of the patients , and more importantly , the fact that we did not compare predialysis and postdialysis qtc interval .\nwe could not find any study on the correlation of qtc interval with lvh or valvular heart disease in hd patients ; however , there are some studies related to the correlation of qtc and lvh with other diseases or conditions .\nfor example , mayet et al . reported that qtd has correlated with left ventricular mass index in hypertensive individuals .\nfound that in athletes , lvh induced by physical training activity is not associated with an increase in qtd , whereas pathological increase in lvh secondary to hypertension could increase qtd .\nthe study of dimopoulos et al . on the evaluation of qtd and left ventricular mass index in elderly hypertensive and normotensive patients reported that hypertensive patients had greater left ventricular mass index and higher qtd .\nthe study had some limitations such as small sample size and lack of qtc measurement after hd session and comparison of it before and after procedure .\nby our knowledge , this is one of the first studies on the correlation of qtc or qtd with valvular abnormality and lvh in hd patients .\nthere were a few studies about the relationship of qtc and lvh in nonrenal patients , so we could not compare our results with other studies .\nbased on our results , in hd patients , qtc interval or qtd was not correlated with echocardiographic findings or laboratory exam results .\ntherefore , it can be concluded that qtc interval prolongation probably has not any correlation with cardiac mortality of the hd patients .", "answer": "introduction : cardiovascular disease is the most common cause of mortality in dialysis patients . chronic renal failure and hemodialysis ( hd ) patients may have longer corrected qt ( qtc ) interval compared with the normal population . \n long qtc interval may be a predictor of ventricular arrhythmia and cardiovascular mortality in these patients and hence the aim of this study was the evaluation of the relationship between qtc interval and some echocardiographic findings and laboratory exam results in hd patients.materials and methods : in a cross - sectional study , 60 hd patients with age > 18 years and the dialysis duration > 3 months were enrolled . \n blood samples were taken , and electrocardiography and echocardiography were done before the dialysis session in the patients.results:mean age of the patients was 56.15 14.6 years . \n qtc interval of the patients was 0.441 0.056 s and qt dispersion ( qtd ) was 64.17 25.93 ms . \n there was no statistically significant relationship between qtc interval and qtd with duration of dialysis , body mass index , age , and gender ( p > 0.05 ) . \n there was also no significant relationship between qtc interval and qtd with mitral regurgitation , tricuspid regurgitation and aortic insufficiency ( p > 0.05 ) . \n in addition , qtc interval and qtd of the patients had not any correlation with serum parathormon and serum ca , k , hco3 ( p > 0.05).conclusion : based on our results , in hd patients , qtc interval and qtd were not correlated with echocardiographic findings or laboratory exam results . \n therefore , it can be concluded that qtc interval prolongation probably has not any correlation with cardiac mortality of the hd patients .", "id": 978} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nan 18-year - old male transferred to the emergency department presented loss of consciousness , cyanosis , and deteriorated vital signs . according to the rescue team transfer records , he called the control center himself because he was home alone .\nhe complained of aggravating dyspnea after eating dinner and of sudden onset vomiting . during ambulance transfer\nthe patient could not remember what happened after the arrival of the rescue team at his house and had no memory of his stay at the emergency room and intensive care unit ( icu ) .\nupon arrival to the emergency room , the patient presented with a cyanotic lip , stupor or semi - comatose mental state , and severe tachyarrhythmia .\nendotracheal intubation was performed immediately . after drawing blood for an emergency laboratory study and portable chest x - ray ,\n1 ) , a large bore needle ( 16 g ) was inserted into the second intercostal space of the mid - clavicular line to decompress intrathoracic pressure .\nimmediately after insertion of the needle , percutaneously checked sao2 increased dramatically to higher than 95% . closed bilateral thoracostomy followed , using a 24 fr chest tube .\nthe patient was transferred to the icu for close monitoring of the patient 's mental state and other parameters related to tension pneumothorax .\nthe abga results upon arrival and after insertion of the chest tube were a ph of 7.272 , pco2 of 56.1 mmhg , po2 of 78.6 mmhg , and sao2 78.6% , and a ph of 7.373 , pco2 of 42.7 mmhg , po2 of 171.3 mmhg , and a sao2 of 99.3% , respectively .\nwithin several hours after admission into the icu , the patient 's mental state and vital signs were restored to within normal limits .\ntwo hours after admission into the icu , endotrachial intubation was removed and spontaneous breathing was maintained with an adequate sao2 level .\nthe possibility of hypoxic brain damage was evaluated by a neurosurgeon , who confirmed that there were no significant sequela . on the second day at the hospital ,\nbilateral pneumothorax recurred during the application of continuous negative wall suction ( -18 cmh2o ) .\nthe operation was performed under general anesthesia with double - lumen endotracheal intubation . to avoid hemodynamic instability during the operation ,\nthe patient was positioned with the head elevated 30 degrees ( semifowler 's position ) and with the legs slightly elevated , with both upper arms extended . during the operation , to improve the operation field view , the operation table was tilted to the contralateral side ( fig .\na large bullae on the left lung and single giant bulla on right upper lung were resected with an endo - gia linear stapling device .\none long thoracic drain ( 28 fr ) was inserted bilaterally into the thoracic cavity after mechanical abrasion of upper portion of the parietal pleura .\nthe incidence of simultaneous bilateral primary spontaneous pneumothorax has been reported to be as low as 1.4% to 7.6% .\nsimultaneous bilateral primary spontaneous pneumothorax can result in a severely deteriorated condition , usually requiring intubation or resuscitation .\nthe reported causes of bilateral pneumothorax include trauma , tumor , and iatrogenic causes [ 1 - 3 ] .\nother more rare causes have been reported , including catamenial pneumothorax , sarcoidosis , pregnancy , and radiation .\nsimultaneous spontaneous bilateral tension pneumothorax is defined as when no tracheal shift occurs and when the degree of bilaterally lung collapse is similar in a chest x - ray .\npatients with simultaneously developed bilateral tension pneumothorax may deteriorate rapidly , and immediate decompression is recommended .\na vicious cycle may occur , leading to a deteriorated condition , with a chain reaction consisting of lowered venous return , lowered preload , lowered cardiac output and so on .\nthe patient under study experienced a critically life threatened state , loss of consciousness , cyanosis , and tachyarrhythmia .\nthe treatment methods include needle aspiration , percutaneous catheter drainage , and tube thoracostomy [ 1 - 4 ] .\nindication for surgical management of pneumothorax include continuous air leakage after insertion of chest tube , recurring pneumothorax on the same side , simultaneous bilateral pneumothorax , pneumothorax developed after pneumonectomy , and having an occupational cause . at present , video - assisted thoracic surgery ( vats ) is the most frequently used form of surgery for treating pneumothorax .\nkim et al . reported a series of 66 patients that were randomized to treatment with either transaxillary minithoracotomy ( tamt ) or vats .\nfirst , a smaller incision was required when compared with tamt , which generally resulted in less pain .\nsecond , the cosmetic effect is superior to that of tamt . finally , most procedures are possible ( mechanical pleurodesis , chemical pleurodesis , etc . ) . prospective studies of simultaneous bilateral spontaneous pneumothorax management are rare .\ngenerally , cases of bilateral pneumothorax require definitive surgical therapy to reduce the risk of recurrence .\nthis can be done either through vats or open thoracotomy , depending on the surgeon 's preference .\nour case presented the rare clinical situation of simultaneous bilateral tension pneumothorax , and a decision was made to treat with immediate large size needle decompression at the emergency room by a properly trained doctor .\nthe procedure was a critical step which restored this patient from life - threatening tension pneumothorax .", "answer": "spontaneous pneumothorax is a common clinical problem in emergency care . \n however , the overall incidences of primary spontaneous pneumothorax has been reported from as low as 1.4% to 7.6% . \n the clinical findings of simultaneous bilateral spontaneous pneumothorax can be variable . \n clinical presentation is variable , ranging from mild dyspnea to tension pneumothorax . \n bilateral tension pneumothorax can defined as cases where no tracheal deviation is detected in chest x - ray , and symptoms may be equal bilaterally . herein , we present a case with simultaneous bilateral tension pneumothorax , severely deteriorated ( i.e. with loss of consciousness , cyanosis , and hemodynamically unstable ) , that was successfully treated with immediate large - size needle decompression .", "id": 979} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is widely accepted that mutation is the main causal factor for diverse tumorigenesis [ 1 , 2 ] .\nthe recent development of next - generation sequencing ( ngs ) technologies has revolutionized the speed and throughput of dna sequencing , which facilitates the discovery of new driver mutations .\nfor example , the arid1a gene is mutated in 83% of gastric cancers with microsatellite instability and the sf3b1 gene is somatically mutated in 9.7% of chronic lymphocytic leukemia patients [ 4 , 5 ] . in colorectal cancers , although the majority of recurrent mutations have been previously known , some novel mutations , such as the mutations in the sox9 and fam123b genes , were also identified by ngs technology , which may have implications for colorectal tumorigenesis . in melanoma , approximately 40% was found to have causal mutations affecting b - raf function .\nalong with the well - known driver mutations , the novel mutations identified by ngs will be useful for predicting the prognosis and molecular characterization of cancers [ 8 , 9 ] .\nrecently , a number of mutation calling tools , such as varscan , genome analysis toolkit , and mutect , have been developed to detect single - nucleotide variants ( snvs ) or indels from ngs data . however , snv calling from a single cancer case is not the final step for defining clinically meaningful mutations . to define the pathogenic snvs in human cancers ,\na commonly used approach is to identify the phenotype - associated recurrent mutations in the study group . due to the data size burden of ngs output , profiling the mutations associated with a certain phenotype or prognosis in a study group by a researcher who does not have a bioinformatics background or facilities\nis very difficult . currently , there is no user - friendly tool supporting methods for the detection of recurrent or phenotype - specific mutations . in this study , in order to support the definition of recurrent mutations or phenotype - specific mutations from ngs data of a group of cancers with diverse phenotypes , we aimed to develop a user - friendly tool , named mutation arranger for defining phenotype - related snv ( map ) .\nmap software was designed as a standalone program , compatible in microsoft windows environments with a user - friendly graphic interface , and compiled codes of map can be easily installed .\nboth variant call format and its annotation files , such as annovar output , can be used as input files for map .\nwhen a user loads the input file , called sample descriptor file ( gsf ) , map software displays the sample set information and filter options ( fig .\n1 ) . once data are loaded , the user can filter the data using the ' analysis options ' tab in map software based on annotation information . by using the sample set and analysis options\nsummary metrics include the mutation status for each sample , total mutation frequency , p - values for differences between phenotype groups based on clinical information , genomic position , reference / observed sequence , and additional information , such as read depth by default . map software also displays more detailed information in summary metrics based on the user - selected ' analysis options . ' in the ' analysis result ' tab , map software provides the frequency- or p - value - based filter function .\nthis functionality supports detection of the recurrent mutations in study subjects and identification of the phenotype - specific mutation that occurs significantly in a certain phenotypic subclass .\nthen , map software represents the user - selected mutations graphically in the ' visualization ' tab . to sort the variants by genomic position , p - value , or frequency , users can use the sort function in the ' analysis result ' tab .\ndetails of the program download , installation , and analysis procedures are available in the user manual .\nthe major steps of map are as follows . \n - generating mutation summary metrics in study subjects- determination of recurrent mutations by frequency- determination of phenotype - specific mutations by association test- graphical illustration of user - selected mutations \n - generating mutation summary metrics in study subjects - determination of recurrent mutations by frequency - determination of phenotype - specific mutations by association test - graphical illustration of user - selected mutations\nmutation calling files from genome analysis toolkit can be used directly as input files for ' sample descriptor . ' alternatively , manually prepared standard variant call format is also available .\nannotation information files , such as annovar outputs , can be used as input files for sample descriptor .\ngsf is a comma - separated values text file that describes the input files , such as gatk output files and annovar output files , and phenotype information .\nwhen users load the input file , map software displays the sample set information and filter options in the ' source ' tab .\nif any file is not prepared properly , map software informs the user in the ' sample set files ' tab .\nafter data are loaded , the user can filter the data using the ' analysis option ' tab based on annotation information .\nbased on user - selected filters in the ' analysis options ' tab , summary metrics represent additional annotation information , such as gene name , function , known variant , and amino acid change .\nthe additional annotations can be hidden using the snp filter option in the ' analysis option ' tab .\nthese mutation metrics are exported into a comma - separated values text file for further investigation .\nin the ' analysis result ' tab , map software defines the recurrent mutations in study subjects by frequency .\nthe frequency threshold can be determined arbitrarily by the user in the ' frequency filter ' function .\nmap also defines the phenotype - specific mutations using the mutation metrics and phenotype information .\nphenotype - specific mutations that occur more frequently in one of two clinical conditions ( e.g. , drug - responder vs. non - responder ) are determined by chi - square test under the user - defined significance level .\nthe graphic user interface is implemented in the software for users to easily handle large - scale data or access the analysis result ( fig . 2b and 2c ) .\nthe recurrent or phenotype - specific mutations can also be demonstrated visually in heat - map style .\nfor example , the left and right of the heat - map represent the sample name and mutational spectrum , respectively .\nthe bottom of the heat - map represents the gene name by color for mutational spectrum . frequency or p - value plots\nare represented on top of the heat - map ( fig . 2b and 2c ) .\nmap is a user - friendly program with multiple functions that supports the determination of recurrent or phenotype - specific mutations and provides graphic illustration images to the users .\nits operation environment , microsoft windows , enables more researchers who can not operate linux to define clinically meaningful mutations with ngs data from cancer cohorts .", "answer": "next - generation sequencing ( ngs ) is widely used to identify the causative mutations underlying diverse human diseases , including cancers , which can be useful for discovering the diagnostic and therapeutic targets . currently , a number of single - nucleotide variant ( snv)-calling algorithms are available ; however , there is no tool for visualizing the recurrent and phenotype - specific mutations for general researchers . in this study , in order to support defining the recurrent mutations or phenotype - specific mutations from ngs data of a group of cancers with diverse phenotypes , we aimed to develop a user - friendly tool , named mutation arranger for defining phenotype - related snv ( map ) . \n map is a user - friendly program with multiple functions that supports the determination of recurrent or phenotype - specific mutations and provides graphic illustration images to the users . \n its operation environment , the microsoft windows environment , enables more researchers who can not operate linux to define clinically meaningful mutations with ngs data from cancer cohorts .", "id": 980} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nbile cast syndrome ( bcs ) is a complication of orthotopic liver transplantation ( olt ) .\nwe describe 2 patients with bcs who were successfully diagnosed with endoscopic retrograde cholangio pancreatography ( ercp ) and one of whom was successfully treated endoscopically .\na 65-year - old female underwent olt 6 months prior to presentation for chronic hepatitis c and hepatocellular carcinoma .\nher intraoperative course during liver transplantation was complicated by a significant amount of blood loss from hepatic veins .\nshe had a complicated postoperative course including hemorrhagic shock , abdominal compartment syndrome and acute renal failure which required hospitalization for 2 months after the transplantation .\nshe developed an anastomotic bile leak which was treated with placement of a 10 fr stent . at 4 weeks and 8 weeks after initial ercp ,\nthe cbd stents were exchanged and secondary sclerosing cholangitis was suspected based on cholangiographic appearance .\nher immunosuppression regimen included tacrolimus 9 mg bid and mycofenolic acid 180 mg bid .\nlaboratory data showed bilirubin of 1.1 mg / dl ( reference range : 0.2 mg / dl-1.3 mg / dl ) , alanine aminotransferase of 53 iu / l ( reference range : 13 iu / l-69 iu / l ) , aspartate aminotransferase of 60 iu / l ( reference range : 15 iu / l-46 \niu / l ) , alkaline phosphatase of 257 iu / l ( reference range : 42 iu / l-140 \niu / l ) , -glutamyl transferase of 466 iu / l ( reference range : 5 iu / l-55 \nballoon sweeps yielded a small amount of debris , but cholangiographic findings persisted that were concerning for filling defects or marked ductal irregularity in the region of the common hepatic duct and bifurcation .\ncholangioscopy ( fig . 2 ) was performed with the spyglass single operator biliary visualization system ( boston scientific , natick , ma , usa ) .\na tubular biliary cast , in the shape of the bile duct , was seen in the donor bile duct extending from the anastomosis into the intrahepatic ducts .\nattempts to extract the cast with a snare , basket , mechanical lithotripter , balloon , spybite(boston scientific , natick , ma , usa ) biopsy forceps , and standard egd forceps were all unsuccessful due to inability to grasp the cast and tethering of the cast to intrahepatic extension . a 10 fr 12-cm cbd stent was placed . in subsequent months ,\nit appears to contain filling defects which retrospectively are related to presence of biliary cast material in the right and left main hepatic ducts . \n\na 58-year - old male with a history of hepatitis c and cirrhosis presented with fevers , chills , and a headache .\nthe patient s immunosuppression regimen included mycophenolate 360 mg bid , prednisone 5 mg daily and tacrolimus 8 mg bid .\nlaboratory data showed bilirubin of 2.2 mg / dl ( reference range : 0.2 mg / dl-1.3 mg / dl ) , alanine aminotransferase of 162 iu / l ( reference range : 13 iu / l-69 iu / l ) , aspartate aminotransferase of 159 iu / l ( reference range : 15 iu / l-46 \niu / l ) , alkaline phosphatase of 1277 iu / l ( reference range : 42 iu / l-140 iu / l ) and white blood cell count of 8.17 10 cells / l .\nthe left main hepatic duct was dilated with a 4-mm dilating balloon to facilitate clearance of the filling defects .\ncholangiogram prior to intervention shows diffuse stricturing of the left and right hepatic ductal system in patient 2 .\nb cholangiogram after removal of the biliary cast showing a widely patent left hepatic duct in patient 2 . \n\nsubsequent to removal of the biliary cast , endoscopic treatment for the anastomotic stricture resulted in resolution of the stricture .\na 65-year - old female underwent olt 6 months prior to presentation for chronic hepatitis c and hepatocellular carcinoma .\nher intraoperative course during liver transplantation was complicated by a significant amount of blood loss from hepatic veins .\nshe had a complicated postoperative course including hemorrhagic shock , abdominal compartment syndrome and acute renal failure which required hospitalization for 2 months after the transplantation .\nshe developed an anastomotic bile leak which was treated with placement of a 10 fr stent . at 4 weeks and 8 weeks after initial ercp ,\nthe cbd stents were exchanged and secondary sclerosing cholangitis was suspected based on cholangiographic appearance .\nher immunosuppression regimen included tacrolimus 9 mg bid and mycofenolic acid 180 mg bid .\nlaboratory data showed bilirubin of 1.1 mg / dl ( reference range : 0.2 mg / dl-1.3 mg / dl ) , alanine aminotransferase of 53 iu / l ( reference range : 13 iu / l-69 iu / l ) , aspartate aminotransferase of 60 iu / l ( reference range : 15 iu / l-46 \niu / l ) , alkaline phosphatase of 257 iu / l ( reference range : 42 iu / l-140 \niu / l ) , -glutamyl transferase of 466 iu / l ( reference range : 5 iu / l-55 \nballoon sweeps yielded a small amount of debris , but cholangiographic findings persisted that were concerning for filling defects or marked ductal irregularity in the region of the common hepatic duct and bifurcation .\ncholangioscopy ( fig . 2 ) was performed with the spyglass single operator biliary visualization system ( boston scientific , natick , ma , usa ) .\na tubular biliary cast , in the shape of the bile duct , was seen in the donor bile duct extending from the anastomosis into the intrahepatic ducts .\nattempts to extract the cast with a snare , basket , mechanical lithotripter , balloon , spybite(boston scientific , natick , ma , usa ) biopsy forceps , and standard egd forceps were all unsuccessful due to inability to grasp the cast and tethering of the cast to intrahepatic extension . a 10 fr 12-cm cbd stent was placed . in subsequent months ,\nit appears to contain filling defects which retrospectively are related to presence of biliary cast material in the right and left main hepatic ducts . \n\na 58-year - old male with a history of hepatitis c and cirrhosis presented with fevers , chills , and a headache .\nhe underwent deceased donor liver and kidney transplantation two months prior to his presentation . the patient\ns immunosuppression regimen included mycophenolate 360 mg bid , prednisone 5 mg daily and tacrolimus 8 mg bid .\nlaboratory data showed bilirubin of 2.2 mg / dl ( reference range : 0.2 mg / dl-1.3 mg / dl ) , alanine aminotransferase of 162 iu / l ( reference range : 13 iu / l-69 \niu / l ) , aspartate aminotransferase of 159 iu / l ( reference range : 15 iu / l-46 \niu / l ) , alkaline phosphatase of 1277 iu / l ( reference range : 42 \niu / l-140 iu / l ) and white blood cell count of 8.17 10 cells / l .\nthe left main hepatic duct was dilated with a 4-mm dilating balloon to facilitate clearance of the filling defects .\n4 ) . following extraction , cholangiograms revealed a widely patent left main duct ( fig . \ncholangiogram prior to intervention shows diffuse stricturing of the left and right hepatic ductal system in patient 2 .\nb cholangiogram after removal of the biliary cast showing a widely patent left hepatic duct in patient 2 . \n\nsubsequent to removal of the biliary cast , endoscopic treatment for the anastomotic stricture resulted in resolution of the stricture .\nbile casts occur in 4 % to 18 % of olt recipients 1 .\nmore than 70 % of casts are identified in the first 16 weeks after transplant 1 .\nbile casts are dark and hard in appearance and formed by lithogenic material confined to the bile duct dimensions 3 \n 4 .\nalthough the exact mechanism of injury is unknown , ischemic injury to the biliary epithelium is most common 5 \n 6 \n 7 .\nother mechanisms including anastomotic and non - anastomotic strictures leading to accumulation of biliary sludge can lead to formation of casts 5 .\nbacterial infection and stones are also predisposing factors for biliary ductal injury and cast formation 6 .\nmicrocirculatory dysfunction is also suggested , given the higher prevalence of renal failure and need for renal replacement therapy in patients with bcs 7 .\na combination of endoscopic interventions is considered including sphincterotomy , balloon and basket extraction , lithotripsy and stent placement . in one study ,\nre - transplantation and 12-month mortality rates were significantly higher with bcs ( 30 % vs. 7 % ) and bcs patients also required a longer intensive care unit stay post - olt 7 .\nsuccess rates with endoscopic therapy for bcs have been reported to be 70 % recently 7 .\npreviously in a large study of post - olt adverse events , biliary cast syndrome occurred in 4/260 patients and a median of 3.5 ercp treatments attempted over a median of 21 weeks achieved a success rate of 25 % 8 .\npercutaneous drainage has also been advocated , especially in the setting of cholangitis or with roux - en - y choledochojejunostomy .\npercutaneous transhepatic choledocoscopy via a tract created with radiographic assistance is a novel approach used for management of bcs . when there is intrahepatic biliary system involvement , management becomes even more challenging .\nretransplantation is considered when complete removal is not feasible and if the patient s clinical condition deteriorates 2 \n 7 . a combined endoscopic and percutaneous method was able to successfully clear the casts in 60 % of patients in one study 9 .\nsurgical intervention including hepaticojejunostomy , choledochojejunostomy and revision of choledochocholedocostomy reportedly has had success rates above 85 % 10 .", "answer": "background and study aims bile cast syndrome ( bcs ) is a complication of orthotopic liver transplantation ( olt ) . \n it occurs in 4 % to 18 % of olt recipients and can present as cholangitis and graft damage or loss \n . twenty - two percent of patients with bcs require repeat olt . \n the diagnosis and management of bcs can be challenging . \n our aim is to share our experience with bcs and to briefly review the diagnosis and management of the condition .", "id": 981} {"query": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `` and `
`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nAn improved procedure for the preparation of Ru(bpz)3(PF6)2 via a high-yielding synthesis of 2,2\u2019-bipyrazine\n\nPaper sections:\nFindings\nVisible light-photoredox catalysis using transition metal chromophores is rapidly becoming recognized as an important strategy in organic synthesis [1\u20135]. This approach towards reaction design enables the facile generation and exploitation of odd-electron intermediates such as radicals and radical ions under exceptionally mild reaction conditions. A large number of transition metal chromophores with well-characterized photophysical and electrochemical properties are known, and the influence of ligand modification on the photoredox properties of these complexes is well understood [6\u20138]. As a result, a variety of Ru and Ir based chromophores spanning a range of redox potentials have recently become widely utilized in the design of new photocatalytic transformations [9].
In particular, the homoleptic tris(bipyrazyl) complex 2 (Ru(bpz)32+) [10] has emerged as one of the most useful transition metal photocatalysts for oxidatively induced organic transformations (Figure 1). Due to the electron-deficient nature of its bipyrazyl ligands, the excited state redox potential of 2 is quite positive (+1.45 V vs SCE) [11]. Consequently, it is an effective photocatalyst in oxidatively induced photoredox transformations where less strongly oxidizing complexes (e.g., 1) are not successful. For instance, we have reported that 2 is uniquely capable of promoting radical cation mediated Diels\u2013Alder cycloadditions [12], radical thiol\u2013ene couplings [13\u201314], and photooxygenation reactions [15\u201316]. Similarly, Zheng has reported oxidatively initiated indole synthesis [17] and [3 + 2] cycloaddition [18\u201319] reactions using photocatalyst 2. Finally, a variety of transition metal complexes bearing bipyrazyl ligands have been prepared and investigated for a wide range of applications in inorganic and organometallic chemistry [20\u201325].
\n\n\nInfluence of ligand structure on photoredox behavior.
\n\nFindings\nUnfortunately, the synthesis of 2,2'-bipyrazyl (bpz) is quite challenging compared to the syntheses of other, structurally similar bidentate bisazene ligands. Various methods for the preparation of bpz have been reported [26\u201328], the most common of which involve transition metal-catalyzed reductive homocouplings of halopyrazine electrophiles [29\u201330]. However, we found these procedures to be capricious in our hands, and after a survey of known reductive dimerization protocols, the highest yields of bpz we were able to obtain resulted from a Pd-catalyzed procedure reported by Pl\u00e9 (Scheme 1) [31]. Using this protocol, we were able to obtain only 40% yield of the desired 2,2-bipyrazine ligand on milligram scale, accompanied by a significant degree of undesired reductive dehalogenation. Moreover, the yields on larger scales were unreliable, and work-up and purification of this inefficient coupling reaction proved difficult.
\n\n\nPd-catalyzed reductive coupling of 2-chloropyrazine.
\n\nFindings\nThus, in order to accelerate our investigations of complex 2 as a strongly oxidizing photoredox catalyst, we required a robust, high-yielding, and scalable synthesis of bpz. An improved synthesis of this ligand would be useful both in the context of the growing interest in photoredox catalysis as well as other organometallic and inorganic applications of bpz-supported transition metal complexes.
Our optimization studies for the reductive coupling of 2-halopyrazines are summarized in Table 1. Initial exploratory experiments using 2-chloropyrazine as the substrate gave quite poor yields using either organic or inorganic bases (Table 1, entries 1 and 2). Speculating that oxidative addition into the aryl chloride bond might be problematic in this coupling reaction, we turned our attention towards the use of more reactive aryl iodides. A screen of solvents commonly used in Pd-catalyzed cross-coupling reactions revealed that DMF provided the highest yields (Table 1, entries 3\u20135). We next examined the effect of varying equivalents of the terminal reductant, and we observed that the presence of excess isopropanol had little effect (Table 1, entries 6 and 7). Finally, an evaluation of the reaction temperature revealed that the coupling proceeded sluggishly at lower temperatures (Table 1, entry 8). Optimal conditions thus called for 5 mol % Pd(OAc)2, 2 equiv of isopropanol, and 1.5 equiv of K2CO3 in DMF (0.4 M) at 100 \u00b0C; under these conditions, the reaction was complete in 2 h and afforded the desired homocoupling product in 81% isolated yield (Table 1, entry 9).
\n\n\nOptimization of Pd-catalyzed reductive homocoupling of 2-halopyrazines.a
aConditions: Reactions were conducted on a 0.22 mmol scale using 1 equiv 2-halopyrazine, 5 mol % Pd(OAc)2, and 1.5 equiv K2CO3 at 100 \u00b0C unless otherwise noted. bYields determined by 1H NMR analysis using an internal standard. cReaction conducted using 1.5 equiv iPr2NEt instead of K2CO3. dReaction conducted at 60 \u00b0C. eReaction conducted for 2 h. fValue in parentheses is the average isolated yield from two reproduced experiments.
\n\nFindings\nAlthough our investigations were motivated by our specific need to access photocatalyst complex 2, we were pleased to find that the optimal conditions for the synthesis of 2,2'-bipyrazine translated smoothly to the reductive coupling of a variety of pyridyl electrophiles. Table 2 demonstrates the application of these reaction conditions to the syntheses of a number of electron-deficient bipyridyl ligands that have been used to prepare strongly photooxidizing metal\u2013polypyridyl complexes [32\u201336]. In each case, the requisite aryl iodides are either commercially available or can be easily synthesized by Finkelstein displacement of the aryl chloride with NaI [37].
\n\n\nPd-Catalyzed synthesis of other ligands used to support electron-deficient Ru(II) chromophores.a
aConditions: 1.0 equiv 2-iodopyrazine, 1.5 equiv K2CO3, 2 equiv isopropanol, 5% Pd(OAc)2, DMF (0.4 M), 100 \u00b0C. bIsolated yield (average of two experiments).
\n\nFindings\nFinally, we explored the scalability of the optimized conditions, and found that they remained applicable on multi-gram scale (Scheme 2). Thus, exposure of 4 g of 2-iodopyrazine to the optimized conditions from Table 1 cleanly produced 1.25 g of 2,2'-bipyrazine in 81% isolated yield. A portion of this material was then carried on to synthesize 689 mg (83% yield) of Ru(bpz)3PF6, showing for the first time that we could efficiently prepare hundreds of milligrams of this important photocatalyst. Importantly, this protocol has proven to be reproducible in the hands of other researchers as well [38].
\n\n\nPreparative-scale synthesis of Ru(bpz)3(PF6)2.
\n\nFindings\nIn conclusion, we have developed an improved, Pd-catalyzed method for the synthesis of 2,2'-bipyrazine, an important ligand with growing utility in the context of visible light photocatalysis. This method is readily scalable to enable the gram-scale preparation of 2,2'-bipryazine, which facilitates the preparative synthesis of the strongly oxidizing photocatalyst Ru(bpz)3(PF6)2 [39].
\n\n\nExperimental section.
", "answer": "There has been a recent surge of interest in the use of transition metal polypyridyl complexes as visible light-absorbing photocatalysts for synthetic applications. Among the most attractive features of this approach is the availability of many known complexes with well-characterized photophysical and electrochemical properties. In particular, Ru(bpz)32+ is a powerful photooxidant that has proven to be uniquely suited for oxidatively induced photoredox transformations. We present here a straightforward and high-yielding route to Ru(bpz)3(PF6)2 that features an improved Pd-catalyzed synthesis of the 2,2\u2019-bipyrazine ligand that is amenable to gram-scale preparations.", "id": 982} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe reviewed the medical records of patients who had l. monocytogenes isolated from blood and body fluids from sterile sites during 19962008 at the national taiwan university hospital ( ntuh ) , a 2,500-bed hospital in taiwan .\nwe evaluated disease severity using modified acute physiology and chronic health evaluation ii scores ( 8) .\nincidence of nontyphiodal salmonella bacteremia ( ntsb ) during 20002008 in ntuh was calculated for trend comparison of the 2 foodborne illnesses .\nonly 1 episode was calculated during the same admission for ntsb to avoid the influence of repetitive bacteremia .\nisolates from patients with fetomaternal listeriosis ( i.e. , paired isolates from mother and neonate who had listeriosis ) were considered to be the same and only 1 of them was analyzed .\nall isolates were analyzed for their serotype by pcr as described , and genetic relatedness was evaluated by pulsed - field gel electrophoresis ( pfge ) by using pulsenet standardized protocols and 2 restriction enzymes ( asci and apai ) ( 2,9 ) .\nstrains were considered to be of the same cluster if their bands had indistinguishable restriction patterns by both enzymes .\nstrains with pfge patterns with > 80% similarity by asci and apai profiles were considered to be closely related .\na forward stepwise model with a p value of 0.1 was used , and p<0.05 was considered statistically significant in the multivariate cox proportional hazards model . during the study period ,\nlisteriosis was diagnosed in 48 patients , and 46 nonduplicated isolates were obtained for further microbiological analysis .\naverage annual incidence increased from 0.0287 cases per 1,000 admissions during 19962004 to 0.118 cases per 1,000 admissions during 20052008 ( figure 1 ) .\nthe increase in annual incidence of listeriosis was significantly correlated with years ( p = 0.0045 ) .\nthe average annual incidences of ntsb were 1.189 and 1.118 per 1,000 admissions during 20002004 and 20052008 , respectively ; it was not significantly correlated with years ( p = 0.50 ) .\nage - specific incidence of listeriosis increased at both extremes of age , but especially among patients > 80 years ( figure 2 ) .\nall of the patients with listeriosis lived in northern taiwan , and no obvious geographic correlation was observed between listeriosis patients in each year .\nincidence ( cases per 1,000 admissions ) of human listeriosis and serotype distribution of all isolates , national taiwan university hospital , taipei , taiwan , 19962008 .\nforty - six isolates were available for analysis , including 2 serotype 4b isolates from fetomaternal transmission in 2005 and 2006 and 1 serotype 4b from a pediatric patient ( 2005 ) .\npatient distribution and incidence of human listeriosis , by age group , national taiwan university hospital , taipei , taiwan , 19962008 .\nall 43 patients had underlying predisposing conditions , and 18 ( 42% ) were > 65 years of age . of the 30 patients with malignancies , 23 ( 77% )\n one female patient had coexisting non - hodgkin lymphoma and colon cancer ; 1 male patient had coexisting non - hodgkin lymphoma , gastric cancer , and bladder cancer . \ninitial modified acute physiology and chronic health evaluation ii score , mean sd : 18.8 7.3 . among the 46 isolates ,\nserotype 1/2b was identified most frequently ( 46% ) , followed by 1/2a ( 28% ) and 4b ( 26% ) .\nall 46 isolates were susceptible to ampicillin , ertapenem , meropenem , and vancomycin ; 3 isolates were intermediately susceptible to trimethoprim / sulfamethoxazole ; and 4 isolates were nonsusceptible to linezolid ( 10 ) .\nsixteen ( 37% ) patients received cephalosporin alone as initial treatment regimens and empirical treatment was effective for only 14 ( 33% ) .\nthe presence of solid - organ malignancies was a significant negative prognostic factor for 14-day mortality in the univariate analysis ( 95% confidence interval [ ci ] 1.16516.694 ; p = 0.029 ) but not in the multivariate analysis .\nthe results of the multivariate analysis for 14-day mortality showed that hepatic decompensation at disease onset was a significant negative prognostic factor ( hazard ratio 12.02 , 95% ci 1.84278.470 ; p = 0.009 ) and that the use of effective antimicrobial drugs after culture results were reported was a significant positive prognostic factor ( hazard ratio 0.014 , 95% ci 0.0020.131 ; p<0.001 ) .\nlog - rank tests performed to compare the difference in survival between patient groups for the 2 variables also had the same results ( p<0.001 ) .\nwe observed an upsurge of listeriosis beginning in 2005 in ntuh . the increase might not be attributable to common - source outbreaks because no clustering was detected .\nthe annual incidence of listeriosis has been on the rise in europe since 2000 ( 2,3,11 ) .\nthe reason is not clear because the increase could not be attributed to outbreak clusters and no increase in pregnancy - related listeriosis was observed ( 2,3 ) .\nwong et al . found that l. monocytogenes was isolated in > 50% of pork samples and chicken carcasses ( 6 ) .\nsemiready foods ( dumplings and meatballs ) and frozen dim sum examined also carried the pathogen ( 34.0% and 4.4% , respectively ) , and > 60% of the isolates were serotype 1 or 4 ( 6 ) . if served undercooked , these foods could be potential transmission sources .\ntaiwan currently has no strict regulatory policy regarding listeriosis in the food industry and no disease surveillance system . in france ,\nserotype 4b was the predominant serotype ( 42%56% ) , whereas serotype 1/2b was more common ( 46% ) in our study ( 2 ) .\nnone of the isolates were resistant to the tested agents , except for 4 isolates , which were resistant to linezolid .\nthe contributions of disease severity and antimicrobial drug treatment are difficult to evaluate in population - based studies ( 12 ) .\nbrouwer et al . reported that up to 30% of adults with l. monocytogenes meningitis did not receive initial adequate antimicrobial drug therapy , and they found no association between that variable and outcome ( 13 ) . a high proportion ( 37% ) of patients in our study\ninitial disease severity and initial adequate antimicrobial drug therapy was not associated with overall mortality .\nwe found that mortality was related to hepatic decompensation and effective antimicrobial drug therapy after culture results were reported .\ntherefore , the incidence of and risk factors for human listeriosis in taiwan could not be determined precisely , and potential outbreaks might have been overlooked .\nthe retrospective design of our study limited the possibility of identifying the potential vehicles and disease - acquiring behaviors .\nan increase of listeriosis was noted since 2005 in our hospital , and all of the affected patients had predisposing factors that hampered their immunity .\ndietary education and food management information should be provided to high - risk groups in taiwan .\nfood monitoring and human disease surveillance systems need to be established in taiwan to control this potentially fatal foodborne disease .", "answer": "during 19962008 , a total of 48 patients with listeriosis were identified at a taiwan hospital . \n average annual incidence increased from 0.029 to 0.118 cases per 1,000 admissions before and after january 2005 . \n serotype 1/2b predominated ; serotype 4b emerged since 2004 . \n food monitoring and disease surveillance systems could help control listeriosis in taiwan .", "id": 983} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe potential use of the affected upper extremity of children with hemiplegia often fails due to learned non - use phenomenon .\nconstraint - induced movement therapy ( cimt ) is one of the treatment strategies which utilizes the principles of neural plasticity to help acquire motor skills of the affected upper extremity.[27 ] this therapeutic approach involves constraining of the unaffected upper extremity using sling , plaster cast , mitt or splints and intensive training of the affected upper extremity with task - specific , goal - oriented activities by reinforcement ( shaping technique ) .\na five - year - old female child presented with right hemiplegia with the history of delayed motor milestones and limited motor skills of the right upper extremity since birth .\nthe objective details of the cause of hemiplegia could not be established as there were no medical records available .\npresently , she has achieved the highest level of functional independence ( able to walk and run independently ) .\nshe displayed no voluntary effort to initiate any motor skills of the right upper extremity unless verbally prompted , even otherwise initiating only minimal response suggesting learned non - use phenomenon .\nthe following criteria were considered for use of cimt in this child ( adapted from cochrane review study ) . \n observed learned non - use of affected upper extremity.a possible movement of at least 10 extension at metacarpophalangeal and inter - phalangeal joints and 20 extension at wrist of the affected upper extremity.no cognitive impairment and shall cooperate with treatment . \n observed learned non - use of affected upper extremity .\na possible movement of at least 10 extension at metacarpophalangeal and inter - phalangeal joints and 20 extension at wrist of the affected upper extremity . no cognitive impairment and shall cooperate with treatment .\nthe quality of upper extremity skills test ( quest ) is a criterion - referenced measure that evaluates the quality of upper extremity function in four domains : dissociated movements ( 19 items with one level of response for each item ) , grasps ( six items with three to five levels of response for each item ) , weight - bearing ( five items with six levels of response for each item ) and protective extension ( three items with six levels of response for each item ) .\nit is designed to be used with children who exhibit neuromotor dysfunction with spasticity and has been validated with children 18 months to eight years of age .\nthe data collected during the neuro developmental therapy / casting study by law et al . , were used to analyze the validity and responsiveness of the quest .\nthe parents of the child were counseled for the treatment approach that could improve the motor skills of the affected right upper extremity .\nthe parents were interested and were keen in subjecting their child to this treatment approach and gave informed consent .\nthe pre - intervention assessments of the right upper extremity motor skills were measured using quest .\nthe unaffected left upper extremity was constrained with posterior slab plaster cast extending above the elbow to the interphalangeal joints of fingers and supported with a sling .\nthe affected right upper extremity was then subjected to task - specific goal - oriented activities that aimed to improve reaching , grasps , manipulation and release of the object using the arm and hand .\nthe activities were encouraged using play way method and reinforcements using visual ( postural mirror ) and verbal feedback .\nthe therapy session usually lasted for one hour a day for five days a week .\nthe parents were instructed to constantly encourage the same activities that were carried out during the treatment session in daily activities . at the end of the two - week period , post - intervention assessment of the right upper extremity was done using quest . as there was an incremental response in the outcome measure ,\nthe investigators convinced the parent to continue the treatment for another week . at the end of three weeks , once again post - intervention assessment was done .\nthe quality of upper extremity skills test ( quest ) is a criterion - referenced measure that evaluates the quality of upper extremity function in four domains : dissociated movements ( 19 items with one level of response for each item ) , grasps ( six items with three to five levels of response for each item ) , weight - bearing ( five items with six levels of response for each item ) and protective extension ( three items with six levels of response for each item ) .\nit is designed to be used with children who exhibit neuromotor dysfunction with spasticity and has been validated with children 18 months to eight years of age .\nthe data collected during the neuro developmental therapy / casting study by law et al . , were used to analyze the validity and responsiveness of the quest .\nthe parents of the child were counseled for the treatment approach that could improve the motor skills of the affected right upper extremity .\nthe parents were interested and were keen in subjecting their child to this treatment approach and gave informed consent .\nthe pre - intervention assessments of the right upper extremity motor skills were measured using quest .\nthe unaffected left upper extremity was constrained with posterior slab plaster cast extending above the elbow to the interphalangeal joints of fingers and supported with a sling .\nthe affected right upper extremity was then subjected to task - specific goal - oriented activities that aimed to improve reaching , grasps , manipulation and release of the object using the arm and hand .\nthe activities were encouraged using play way method and reinforcements using visual ( postural mirror ) and verbal feedback .\nthe therapy session usually lasted for one hour a day for five days a week .\nthe parents were instructed to constantly encourage the same activities that were carried out during the treatment session in daily activities . at the end of the two - week period , post - intervention assessment of the right upper extremity was done using quest . as there was an incremental response in the outcome measure\n, the investigators convinced the parent to continue the treatment for another week . at the end of three weeks\nas the quest measure analyzes the quality of motor skills of both the right and left extremity , it may be noted that the pre - intervention percentage score was 53.04% indicating full percentage score of unaffected left upper extremity and marginal percentage score of affected right upper extremity [ table 1 ] . following intervention , increments in percentage score by 26.79% and 07.51%\nwere observed at the end of two weeks and three weeks respectively which should be attributed to the improvements in the quality of motor skills of the affected right upper extremity .\nit may also be noted that the grasp percentage score was greater than other domains indicating better improvement in fine motor skills than gross motor skills .\nthe main concern for the parents in the use of cimt for improving the motor skills of the affected upper extremity in infantile hemiplegia was the fact that it restricts the use of the unaffected extremity .\nthe success of the use of cimt in infantile hemiplegia depends on the parents , their proper understanding of the concept of the approach and their deep motivation in carrying out home exercises .\nthe increments in percentage scores observed in this case report are attributed to the increased demands for the use of the affected upper extremity while constraining the unaffected upper extremity through task - specific goal - oriented activities that were reinforced with visual and verbal feedback .\nthe observation of this case report indicates that the use of cimt could reverse the learned non - use phenomenon of the affected upper extremity in infantile hemiplegia and thus reduce disability to greater extent .", "answer": "infantile hemiplegia is one of the clinical forms of cerebral palsy that refers to impaired motor function of one half of the body owing to contralateral brain damage due to prenatal , perinatal and postnatal causes amongst which vascular lesion is the most common causative factor . \n we report here the effects of constraint - induced movement therapy in a five - year - old female child with infantile hemiplegia on improvement of upper extremity motor skills .", "id": 984} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\n. \n the baff / april axis plays an important role in the pathogenesis of various autoimmune diseases including sle ; inhibitors of this axis are therefore useful in treatment of these disordersresults from bliss-52 and bliss-76 trials have shown belimumab to be efficacious in treating patients with sleserious adverse effects noted with belimumab such as progressive multifocal leukoencephalopathy , depression , suicidal tendency , and malignancy are to be watched for . \n \nthe baff / april axis plays an important role in the pathogenesis of various autoimmune diseases including sle ; inhibitors of this axis are therefore useful in treatment of these disorders results from bliss-52 and bliss-76 trials have shown belimumab to be efficacious in treating patients with sle serious adverse effects noted with belimumab such as progressive multifocal leukoencephalopathy , depression , suicidal tendency , and malignancy are to be watched for .\n. \n the baff / april axis plays an important role in the pathogenesis of various autoimmune diseases including sle ; inhibitors of this axis are therefore useful in treatment of these disordersresults from bliss-52 and bliss-76 trials have shown belimumab to be efficacious in treating patients with sleserious adverse effects noted with belimumab such as progressive multifocal leukoencephalopathy , depression , suicidal tendency , and malignancy are to be watched for . \n \nthe baff / april axis plays an important role in the pathogenesis of various autoimmune diseases including sle ; inhibitors of this axis are therefore useful in treatment of these disorders results from bliss-52 and bliss-76 trials have shown belimumab to be efficacious in treating patients with sle serious adverse effects noted with belimumab such as progressive multifocal leukoencephalopathy , depression , suicidal tendency , and malignancy are to be watched for .", "answer": "belimumab is the only approved biological agent for the treatment of systemic lupus erythematosus ( sle ) . \n it is a fully humanized igg1 monoclonal antibody directed against soluble b lymphocyte stimulator ( blys ) . \n it is indicated as an add - on therapy for the treatment of adult patients with active , autoantibody - positive sle , who are receiving standard therapy . \n belimumab is generally well - tolerated , common adverse effects include infections , infusion reactions , hypersensitivity , headache , nausea , and fatigue . psychiatric events including suicidal tendency , progressive multifocal leukoencephalopathy and malignancies too have been reported . \n apart from sle , the drug is also being tried for other autoimmune disorders .", "id": 985} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe most commonly used materials for bone implants are metals ( such as titanium , ti ) and polymers ( such as ultra high molecular weight polyethylene ) .\nnumerous problems exist with these implants such as ( i ) insufficient prolonged bonding between the implanted material and juxtaposed bone ( kaplan et al 1994a , 1994b ; buser et al 1999 ; webster 2001 ) , ( ii ) different mechanical properties between bone and the implant leading to stress shielding ( kaplan et al 1994a , 1994b ; webster 2001 ) , and ( iii ) wear debris generated at articulating surfaces of orthopedic implants that may lead to cell death ( kaplan et al 1994a , 1994b ) .\nit has been speculated that nano - structured materials can increase orthopedic implant efficacy since it is well known that the nanometer scale is the length scale that most of the body s natural materials possess .\nfor example , hydroxyapatite , the major inorganic component of bone , exists predominantly as platelet - or rod - shape crystals about 25 nm in width and 50 nm in length .\ntype i collagen , the major organic component of bone , has fibrils 300 nm in length , 0.5 nm in width , and has a periodicity of 67 nm ( park and lakes 1992 ) .\ntherefore , it is reasonable to consider that osteoblasts ( or bone - forming cells ) will be more accustomed to nano - structured surfaces compared to currently used nano - smooth implant surfaces .\nsuch problems with promoting new bone growth next to implant surfaces are made only more complex for patients with bone cancer ( both primary bone cancer and metastasized bone cancers ) .\nfor example , it is estimated that 2,380 people will be diagnosed with bone and joint cancers and 1,470 people will die from primary bone and joint cancers in 2008 in the us ( american cancer society 2008 ) .\nprimary bone cancer is rare but bone cancer as a result of the metastasis from other organs ( such as the lungs , breasts and the prostate ) is very common ( miller and webster 2007 ) .\nthus , the number of patients affiliated with bone cancer is much higher when considering the statistics of cancer metastasis . for these reasons ,\nthe main goal of this study was to introduce a new biomaterial naturally found in the human body that has chemopreventive properties for orthopedic implants : elemental selenium .\nthe first goal in this effort was to create nano - structured roughness on such materials and to determine bone cell responses on such nano - structured selenium materials .\nselenium shots ( amorphous , metals basis , spherical and/or semi - spherical 24 mm in diameter ; alfa asear , ward hill , ma ) were pressed into cylindrical compacts ( 0.635 cm radius and 0.2 cm thickness ) at 1000 psi for 2 minutes using a uniaxial compacting hydraulic press ( carver , inc . ,\nthe compacts were then chemically treated with 1n naoh for either 10 or 30 min . after etching\n, selenium compacts were washed with excessive deionized water to remove the naoh that remained on the selenium compacts .\nsurfaces of untreated selenium compacts as well as selenium compacts treated with 1n naoh for 10 and 30 min were visualized ( without a conductive coating ) using a scanning electron microscope ( sem , leo 1530vp fe-4800 ) with an accelerating voltage from 3 to 10 kv .\nenergy dispersive x - ray spectroscopy ( eds , leo 1530 ) was used to determine the surface chemistry of the compacts . to investigate osteoblast adhesion on selenium compacts , human osteoblast - like cells ( bone - forming cells ; crl-11372 american type of culture collection , population numbers 1415 ) in dulbecco s modified eagle media supplemented with 10% fetal bovine serum ( hyclone ) and 1% penicillin / streptomycin ( hyclone )\nwere seeded at a density of 3500 cells / cm and placed in an incubator under standard cell culture conditions ( 37c , 5% co2 , 95% humidified air ) for 24 h. importantly , this is an immortalized cell line which has been used widely in experiments involving orthopedic applications since previous studies have demonstrated that when cultured under similar conditions as described in the present study , these cells secrete bone - related proteins and deposit calcium containing mineral ( miller and webster 2007 ) .\nlouis , mo ) , stained with 4,6-diamidino-2-phenylindole ( dapi ) ( sigma ) and counted under fluorescence microscopy ( zeiss axiovert 200 m light microscope ) in five random fields which were averaged for each compact .\ndata were collected and statistical comparisons were assessed using a one - tailed student t - test .\nthe sem images of the selenium compacts ( untreated and treated with naoh for different time periods ) revealed various surface roughness .\nuntreated surfaces ( figure 1 image a ) possessed mostly micron rough surface features while those treated with 1n naoh for different time periods created submicron ( figure 1 image b ) and nano - rough ( figure 1 image c ) surface features on selenium . in particular , biologically inspired surface roughness increased with increasing naoh treatment time periods . as the etchant , naoh is believed to dissolve the oxide layer on the surface of the selenium compacts creating submicron and nanometer features at increasing times .\nchemical etching is a very common , inexpensive , and simple method used to modify the surface properties ( eg , topography , chemistry , roughness , wettability , etc . ) of biomaterials .\nchemical etching can be used for a wide range of biomaterials from metals , ceramics , to polymers .\nfor example , etching titanium with hcl followed by naoh has led to the formation of uniform micrometer featured surfaces that increased the formation of hydroxycarbonated apatite when exposed to a simulated body fluid ( jonasova et al 2004 ) .\nmoreover , etching poly ( lactic - co - glycolic acid ) ( plga ) films using naoh has created biologically inspired nanometer surface feature dimensions to promote the functions of numerous cells .\nfor example , this nanometer plga structured surface was shown to promote bladder smooth muscle cell functions compared to conventional , micrometer - structured plga after 1 , 3 , and 5 days of culture ( thapa et al 2003 ) .\nin addition , feldspathic porcelain etched in 5% hydrofluoric acid was shown to promote the bonding strength between orthodontic brackets and ceramic crowns when compared to those treated by mechanical roughening with fine diamond burs or sandblasting ( schmage et al 2003 ) .\nclearly , chemical etching can be an inexpensive effective way to transform nano - smooth surfaces into nano - rough surfaces for a wide range of materials to promote their biological performance .\nimportantly , eds profiles of the compacts used in the present study revealed that the chemistry of the selenium compacts remained unaffected after treatment in 1n naoh ( figure 2 )\n. moreover , table 1 lists the weight percentages of selenium and sodium for each compact .\nthe results showed trace amounts of sodium on the surfaces of selenium compacts treated with 1n naoh .\nthis indicated that chemical etching ( ie , using 1n naoh for up to 30 min ) only changed the surface roughness , not the surface chemistry of the selenium compacts . the ability to change an implant s surface roughness and/or topography without altering\nits chemistry is of great interest since , when fabricating implant materials , it is crucial not to induce any potential harmful chemistry changes . in this study ,\nselenium compact chemistry remained unaltered after treatment with 1n naoh for up to 30 min . when these substrates were used as substrates for culturing osteoblasts , after 1 day , significantly increased cell densities were observed on the increasing nano - rough surfaces ( ie , compacts treated with 1n naoh for 10 and 30 min ) ( figures 3 , 4 ) .\nespecially , the compacts treated with 1n naoh for 30 min , which had the largest amount of nanometer surface features , had the highest osteoblast density . however , although closer , these selenium compacts ( ie , compacts treated with 1n naoh for 30 min ) had osteoblast densities lower than that of titanium .\nfuture studies will need to utilize greater times and/or concentrations of naoh etching to determine if osteoblast adhesion can be matched between selenium and titanium .\nmoreover , future studies will need to examine primary osteoblast cells ( since that was not accomplished here ) as well as the multitude of cancerous cells that can cause bone cancer .\nit has been shown that increased nanometer surface roughness promotes osteoblast functions ( from adhesion to the deposition of calcium containing mineral ) ( webster et al 1999 , 2000a , 2000b ; webster 2001 ; webster and ejiofor 2004 ) .\nthe results of this study showed a similar trend of increased healthy osteoblast densities after 1 day of culture on selenium with increased nanometer surface roughness .\nthe significance of these results is also the introduction of a new chemistry to the orthopedic community particularly geared at inhibiting bone cancer regrowth : selenium .\nselenium has been shown to have chemo - preventive effects in numerous reports ( combs and combs 1986 ; clark et al 1991 , 1998 ; combs and gray 1998 ; navarro - alarcon and lopez - martinez 2000 ; zhuo et al 2004 ; wei et al 2004 ) .\nhowever , the mechanisms of selenium - based chemoprevention are complex and incompletely understood ( combs 2001 ) . by imparting nano features onto selenium compacts ,\nthe objective of this study was to create a material that promotes healthy osteoblast functions since evidence has already been provided concerning its role in inhibiting cancer growth . in the present study ,\nhealthy osteoblast adhesion was shown to be enhanced on nano - rough selenium compacts when compared to micro - rough selenium compacts .\nhowever , it has been shown that nano - roughness effectively increased the initial absorption of proteins ( such as fibronectin and vitronectin ) which mediate subsequent cell adhesion ( webster et al 2000b , 2001 ; khang et al 2007 ) . in particular ,\nparticle boundaries on other material ( ti , ti6al4v , and cocrmo ) surfaces were shown to be active regions for such protein adsorption ( webster and ejiofor 2004 ) .\nnano - structured surfaces clearly offer more particle boundaries when compared to micron - structured surfaces for promoting initial protein adsorption events . in another recent study\n, elemental selenium nanoclusters were coated on conventional titanium substrates to create nano - structured surfaces .\nthese surfaces were shown to promote healthy osteoblast functions after 1 day of culture and , importantly , inhibit cancerous osteoblast cell functions after 3 days of culture ( sarin et al 2008 ) . in the present study ,\nnano - structured selenium surfaces were created by a different method : chemically etching selenium bulk compacts .\nthe approach used in this study is simpler than the coating method used ( which involved selenium chemical precipitation ) and can eliminate the influence of titanium in the interaction with osteoblasts since selenium coatings in that previous study did not completely cover the underlying titanium .\nhowever , considering the toxicity of selenium at high levels ( whanger et al 1996 ) , the use of selenium compacts may be problematic concerning how much selenium is exposed to the body leading to possible toxic effects .\nfuture studies need to clearly investigate this possible toxicity as well as cancerous bone cell functions on these selenium compacts .\nthis study provided techniques to create nano - structured roughness without altering chemistry on selenium compacts for anti - cancer orthopedic applications .\nsince previous studies have shown greater osteoblast functions on nano - structured compared to conventional ceramics , metals , polymers , and composites , the ability to create nano - structured roughness on selenium compacts is promising for increasing bone cell functions , while inhibiting the return of bone cancer .", "answer": "metallic bone implants possess numerous problems limiting their long - term efficacy , such as poor prolonged osseointegration , stress shielding , and corrosion under in vivo environments . such problems are compounded for bone cancer patients since numerous patients receive orthopedic implants after cancerous bone resection . unfortunately , current orthopedic materials were not originally developed to simultaneously increase healthy bone growth ( as in traditional orthopedic implant applications ) while inhibiting cancerous bone growth . \n the long - term objective of the present research is to investigate the use of nano - rough selenium to prevent bone cancer from re - occurring while promoting healthy bone growth for this select group of cancer patients . \n selenium is a well known anti - cancer chemical . \n however , what is not known is how healthy bone cells interact with selenium . to determine this , selenium , spherical or semispherical shots , were pressed into cylindrical compacts and these compacts were then etched using 1n naoh to obtain various surface structures ranging from the micron , submicron to nano scales . \n changes in surface chemistry were also analyzed . through these etching techniques \n , results of this study showed that biologically inspired surface roughness values were created on selenium compacts to match that of natural bone roughness . \n moreover , results showed that healthy bone cell adhesion increased with greater nanometer selenium roughness ( more closely matching that of titanium ) . in this manner \n , this study suggests that nano - rough selenium should be further tested for orthopedic applications involving bone cancer treatment .", "id": 986} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nanti - neutrophil cytoplasmic antibodies ( ancas ) correlate well with a wide spectrum of vasculitis manifestations , including wegener 's granulomatosis , microscopic polyangiitis , and churg - strauss syndrome , all of which are commonly referred to as anca - associated vasculitis ( 1 ) .\nseveral infections , particularly infective endocarditis , have been reported to show positive findings on anca tests ; furthermore , their clinical features have been acknowledged to mimic anca - associated vasculitis , which may lead to a misdiagnosis and inappropriate treatment ( 2,3 ) .\nhowever , to our knowledge , infected aortic aneurysms have not been reported to show positive findings on anca tests .\nwe herein report a patient with an infected thoracic aortic aneurysm mimicking anti - proteinase 3-antineutrophil cytoplasmic antibody ( pr3-anca)-associated vasculitis .\nvegetations in the descending aorta , which were detected using transesophageal echocardiography , contributed to the diagnosis in this case .\na woman in her 60s was admitted to the nagoya city university hospital complaining of a fever , which had persisted for three weeks , along with a loss of appetite , proteinuria , hematuria , and renal dysfunction .\nher renal function test values had been in the normal range three months prior to the admission .\nshe also had a history of orbital mucosa - associated lymphoid tissue lymphoma , which was in remission after treatment with only radiation therapy .\na physical examination at the time of admission revealed a body temperature of 38.1 , pulse rate 109 beats / min , and blood pressure 104/53 mmhg .\nthe laboratory tests revealed a white blood cell count of 18,900/mm , hemoglobin 6.6 g / dl , blood urea nitrogen 30.8 mg / dl , serum creatinine 2.24 mg / dl , and c - reactive protein ( crp ) 9.44 mg / dl ( table ) .\nthe pr3-anca titer was 47.4 iu / ml ( normal range < 10 iu / ml ) , although her myeloperoxidase - antineutrophil cytoplasmic antibody ( mpo - anca ) titer was not elevated .\na urinalysis gave results of 2 + for protein and 3 + for occult blood in a dipstick examination , and a microscopic examination detected more than 100 red blood cells per high - power field .\nalt : alanine aminotransferase , ana : antinuclear antibodies , ast : aspartate transaminase , c3 : compliment 3 , c4 : compliment 4 , ch50 : 50% hemolytic unit of complement , crp : c - reactive protein , dna : deoxyribonucleic acid , ldh : lactate dehydrogenase , mpo - anca : myeloperoxidase - antineutrophil cytoplasmic antibody , rf : rheumatic factor , pr3-anca : anti - proteinase 3-antineutrophil cytoplasmic antibody she was initially diagnosed with pr3-anca - associated vasculitis and was thereafter treated with methylprednisolone pulse therapy ( 500 mg / day ) for three days ( fig .\nhowever , streptococcus sanguis was serially detected in blood cultures ; therefore , the administration of steroids was stopped .\ntransesophageal echocardiography also revealed no vegetation in the heart ; however , it showed many oscillating masses attached to the intima in the descending aorta ( fig .\n2 ) . contrast - enhanced computed tomography ( ct ) revealed a new descending aortic aneurysm ( fig .\neffects of antibiotics on fever and c - reactive protein during hospitalization . the patient finally became afebrile and has c - reactive protein levels within the normal range after receiving antibiotics .\ncrp : c - reactive protein , dap : daptomycin , pcg : penicillin g , taz / pipc : tazobactam / piperacillin , tx : therapy transesophageal echocardiographic images of the descending aorta , with sectioning planes at 90 ( a ) and 0 ( b ) .\nmany oscillating masses attached to the intima were seen in the lumen of the descending aorta .\ncontrast - enhanced computed tomographic images in the axial ( a ) and frontal ( b ) sections .\nthese images show a descending aortic pseudoaneurysm and a contrast defect ( arrow ) beside the aneurysm that is compatible with echo - documented vegetation .\nbased on the results of microbiological testing , antibiotic treatment with intravenous penicillin g ( 24,000,000 unit / day ) was started , after which she became afebrile .\nwe added intravenous daptomycin ( 300 mg every 24 hours ) and tazobactam / piperacillin ( 2.25 g every 6 hours ) to the penicillin g because recurrent fever was observed two weeks later .\nthis additional antibiotic treatment made her afebrile again , and her renal function was recovered ( fig .\n, she developed a janeway lesion , which was confirmed by the pathological finding of a skin biopsy specimen ( fig .\n4 ) . transesophageal echocardiography finally demonstrated that the vegetation had disappeared after the antibiotic treatment ( fig .\n5 ) , but contrast - enhanced ct revealed that the aneurysm remained unchanged in form . a nontender hemorrhagic macular on the sole of the foot ( a ) .\nphotomicrograph of the macular lesion shows microembolization with fibrin and infiltration of neutrophilic cells hematoxylin and eosin staining ( b , c ) .\na transesophageal echocardiographic image of the descending aorta after the antibiotic treatment , with the sectioning plane at 90. many oscillating masses have disappeared . on the 54th hospital day , she underwent endovascular aortic repair ( evar ) of the aneurysm ( fig .\n6 ) after confirmation that her crp level was in the normal range and once blood cultures were consistently negative .\none year after the procedure , she continues to take oral antibiotics ; no complications related to stent - graft deployment or recurrent infections have been encountered .\nher pr3-anca titer has normalized . a contrast - enhanced computed tomographic image after endovascular stent graft repair .\nin this case , an infected aortic aneurysm exhibited elevated the patient 's pr3-anca level , and its clinical course mimicked pr3-anca - associated vasculitis .\nthe detection of ancas is highly specific for a diagnosis of anca - associated vasculitis ( 4 ) ; however , a number of infections can result in a positive anca test .\nthere are several reports of infective endocarditis with the presence of ancas that mimic the clinical manifestations of an anca - associated vasculitis such as glomerulonephritis ( 2,3 ) . in the present case , based on the finding of positive blood cultures\n, we suspected that the patient was experiencing not anca - associated vasculitis but infective endocarditis .\nhowever , no vegetations were detected in the cardiac chambers using transthoracic echocardiography or transesophageal echocardiography .\ninstead , contrast - enhanced ct revealed a pseudoaneurysm in the descending aorta , which suggested that the patient had an infected aneurysm .\nher renal dysfunction and elevated pr3-anca levels normalized with clinical resolution of the infected aneurysm after the administration of appropriate antibiotic therapy and evar .\nthe patient has remained free of any evidence of systemic vasculitis during follow - up .\nthe presence of pr3-anca may have been falsely positive in the present patient . to our knowledge , this is the first report of an infected aortic aneurysm with a positive pr3-anca test and clinical features mimicking anca - associated vasculitis .\nthe presence of vegetations in the heart is one of the most characteristic findings of infective endocarditis .\nthese vegetations are composed of bacteria , platelets , and inflammatory cells interspersed with fibrin mesh , either on damaged endocardium , including native cardiac valves , or prosthetic valves ( 5 ) . in the present case ,\nbecause these masses disappeared after antibiotic treatment , they were considered to be vegetations . a pathological examination of the macular hemorrhages on the patient 's sole indicated not a cholesterol embolization but rather a janeway lesion , which was the consequence of septic embolic events .\nwe therefore suspected that these masses were not mobile plaques but bacterial vegetations . to our knowledge ,\nfew cases of infected native aortic aneurysm manifesting vegetations in the aneurysm have been reported ( 6 - 8 ) .\nseveral mechanisms have been proposed regarding how ancas are formed during the course of infection , such as autoantigen complementarity , molecular mimicry , epigenetics , neutrophil extracellular traps , and microbial - sensing proteins called toll - like receptors ( 9 ) . there may be a great degree of overlap in the clinical and laboratory manifestations between anca - associated vasculitis and anca - positive infected aortic aneurysm , potentially leading to a misdiagnosis .\nit is important to correctly diagnose these cases in order to avoid administering inappropriate therapy , such as immunosuppressive treatment , which might have life - threatening consequences in a patient with an infected aortic aneurysm .\npositive blood cultures and imaging findings , such as a pseudoaneurysm and/or vegetations in the aorta , suggest the presence of an infected aortic aneurysm . a combination of conventional surgical treatment with resection of the aneurysm , extensive local debridement , and revascularization by in situ reconstruction or extra - anatomic bypass may be the gold standard , but such a treatment strategy is accompanied by a high mortality and morbidity . in the present case ,\nit was recently reported that evar of an infected aortic aneurysm is feasible and , for most patients , a durable treatment option ( 10 ) .\ngiven that the continuous administration of antibiotics for the infected aneurysm should prevent a recurrence of local infection , we continued using antibiotics until the infection was controlled and carefully monitored the shape of the pseudoaneurysm on contrast - enhanced ct .\nwe were ready to perform an emergency surgical correction at any point during this patient 's treatment course . in conclusion\n, we herein reported an unusual case of infected descending aortic pseudoaneurysm with luminal pathognomonic oscillating vegetation and with serological findings and clinical features mimicking pr3-anca - associated vasculitis .", "answer": "we herein report an unusual case of an infected descending aortic pseudoaneurysm with luminal pathognomonic oscillating vegetation with serological findings and clinical features mimicking anti - proteinase 3-antineutrophil cytoplasmic antibody - associated vasculitis . the positive blood cultures and imaging findings , including a pseudoaneurysm and vegetations in the aorta , suggested the presence of an infected aortic aneurysm . \n the patient was successfully treated with antibiotics and endovascular aortic repair . \n a precise diagnosis is crucial in order to avoid inappropriate therapy such as immunosuppressive treatment , which could result in life - threatening consequences in a patient with an infected aortic aneurysm .", "id": 987} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\namisulpride came into the indian market a few years back with hypes and hopes in the management of schizophrenia .\nits broad spectrum effectiveness with lower chances of extrapyramidal symptoms ( eps ) and metabolic syndrome did help psychiatrists to treat schizophrenia and related disorders more effectively .\nalthough this antipsychotic does not block serotonin receptors at all , it is a high - affinity and highly selective d3/d2 receptor antagonist with atypical properties .\nits selective affinity for dopamine receptors in the limbic structures , but not in the striatum , leads to a low risk of extrapyramidal side effects .\nall available reports suggest that chance of eps is very less with amisulpride at doses < 400 mg / day .\nhowever , there are sporadic reports of drug - induced eps including dystonia and akathisia even in patients receiving low doses of amisulpride . here\na 30-year - old male with schizophrenia for the past 10 years now presented with predominantly negative symptoms .\nhe was on olanzapine 15 mg / day for more than 6 months without much improvement .\nhence , amisulpride was instituted with a starting dose of 50 mg / day with a gradual increment up to 300 mg / day within 14 days .\nthe patient came after 14 days to the casualty with features of parkinsonian syndrome such as slowed gait , mild rigidity , salivation , and bradykinesia .\nhe was hospitalized , amisulpride was immediately stopped , and trihexyphenidyl 4 mg / day was given to manage the side effect .\nhis eps gradually subsided and for negative symptoms , clozapine was introduced at a small dose of 25 mg / day and gradually increased to 200 mg / day over a period of 10 days . at the time of discharge , on the 14 day , he was free from parkinsonian symptoms .\nsubsequent follow - up showed no parkinsonian symptoms and he had modest improvement in negative symptoms . a 48-year - old male with schizophrenia for the last 20 years\nwas treated with various antipsychotics without much improvement . since the last 6 months , he was on olanzapine 15 mg / day .\nas there was no significant improvement , his olanzapine dose was gradually tapered and stopped over a period of 14 days and was started on amisulpride 100 mg / day and was increased to 200 mg / day over a period of 3 weeks .\nthe patient returned on the 24 day with severe parkinsonian symptoms . in this patient also , there was no prior history of parkinsonism .\nwe managed him with injection promethazine 25 mg intramuscular bid first 3 days along with trihexyphenidyl 2 mg bid after stopping amisulpride .\nafter 7 days , parkinsonian symptoms improved considerably and clozapine was introduced at a dose of 25 mg / day which was subsequently increased to 100 mg / day on the 10 day and the patient was discharged .\nsince the discovery that clozapine induces fewer eps and is more effective for negative symptoms than conventional antipsychotics for the treatment of schizophrenia , psychopharmacological research has focused on the development of drugs that block central 5-ht2 receptors more than d2 receptors .\ncombined 5-ht2/d2 receptor antagonism is the most current explanation for the so - called atypical profile of some antipsychotics .\namisulpride at low doses binds selectively to dopamine d2 , d3 autoreceptors , thereby enhancing dopaminergic transmission and thus might be effective for negative symptoms .\nit has no affinity for d1 , d4 , and d5 receptor subtypes . at higher doses\n, it blocks postsynaptic receptors , thus inhibiting dopaminergic hyperactivity . at the same time , amisulpride has greater specificity for the limbic system and thus has low incidence of eps .\namisulpride binds more loosely than dopamine to the dopamine d2 receptor and is rapidly dissociated from the dopamine d2 receptor .\nlow - dose therapy with amisulpride is associated with a significantly lower blockade of striatal dopamine d2 receptors than is seen during high - dose treatment . however , a significant striatal d2 blockade was demonstrated at therapeutically effective dose ranges , and a good relationship between the degree of striatal dopamine d2 receptor occupancy and the amisulpride plasma concentration or the administered dose was shown . in general , asians are slow metabolizers .\nlow body weight and slow metabolism may increase the plasma concentration of drugs causing side effects .\nreported a low postsynaptic d2 occupancy in the striatum at low doses of amisulpride ( 50100 mg / day ) .\nit has also been suggested that extrastriatal binding could mediate the effect on negative symptoms .\nthe probable causes of eps with low doses of amisulpride could be that it blocks postsynaptic d2 receptors significantly in striatum without much effect in the mesolimbic pathway .\n, the lower incidence of eps which is claimed by western researchers as well as pharmaceutical companies should be studied well in the indian context .\nwe should at least keep this side effect in our minds while starting or increasing the doses .", "answer": "amisulpride , recently introduced atypical antipsychotic , is well - known for its broad spectrum effectiveness and lower profile for extrapyramidal side effects ( eps ) . \n its selective affinity for dopamine receptors in the limbic structures , but not in the striatum , leads to a low risk of extrapyramidal side effects . here \n , we report two cases of eps associated with lower dose of amisulpride . \n the proposed mechanism for its causation is also discussed . \n authors invite more studies , specifically from the indian context to find out the incidence of eps and other associated side effects .", "id": 988} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwandering spleen , also known as ectopic spleen , is an uncommon clinical entity characterized by hypermobility of the spleen due to laxity or absence of the normal ligaments that attach the spleen to the left upper quadrant .\nthis allows the spleen to essentially drop to the lower abdomen by the force of gravity attached only to its abnormally elongated vascular pedicle .\ncommon complications of a wandering spleen include torsion of its pedicle , compression of another organ by the spleen or the pedicle , and susceptibility of the spleen to trauma .\nsymptoms are most commonly attributed to complications related to irreducible torsion which produces venous congestion , arterial infraction , strangulation and rupture of the spleen .\ntreatment of choice is splenopexy for an uncomplicated or complicated but viable wandering spleen and splenectomy for a non - viable spleen .\nherein , we present a case of a patient with progressive torsion of a pelvic spleen causing recurrent abdominal pain and eventually spleen strangulation and rupture .\na 46-year - old male was admitted to the emergency department complaining of constant left lower quadrant abdominal pain of increasing severity for the last 6 days . direct questioning revealed a history of mild , intermittent lower abdominal pain for the past 65 days .\nthe patient was febrile ( 38.8 c ) , had tachycardia ( 118 beats / min ) and blood pressure of 90/50 mmhg .\nphysical examination revealed abdominal distention , predominantly in the hypogastric region due to a tender mass causing dullness on percussion suprapubicly .\npelvic mass or pelvic peritonitis arised from a variety of causes were included in the differential diagnosis .\nabdominal x - rays revealed increased pelvic radio - opaqueness , few dilated loops of small intestine , and displacement of the splenic flexure in the normal spleen position .\nemergency ct revealed absence of the spleen in its normal position , a homogeneous pelvic mass with no contrast enhancement pushing aside the sigmoid colon , free blood in the peritoneal cavity around the mass , and a normal urinary tract .\nthe absence of the spleen in its normal position and the non - enhancement of the pelvic mass made the diagnosis of an ectopic strangulated spleen undeniable .\nthe spleen was enlarged ( 23 cm 18 cm 12 cm ) , located inside the pelvis , attached to an abnormally elongated torted pedicle ( 19 cm ) , and adhered to the greater omentum and intestine ( none of splenic ligaments were present ) ( fig .\nthe spleen was strangulated due to the 760 clockwise twists of its pedicle ( fig .\n2 ) , and ruptured at its lower pole ( 2 cm in depth , not evolving a trabecular vessel grade ii laceration ) .\n3 ) ; however , the organ continued to appear non - viable and total splenectomy was performed .\nthorough investigation revealed no evidence of accessory spleens in the left upper quadrant , the bowel mesentery , the greater omentum and the pelvis . during exploration\nhistology revealed acute thrombotic changes in arteries and veins of the splenic hilum , with diffuse hemorrhagic and ischemic infarcts of the spleen .\nthe postoperative course was uneventful and the patient was discharged on the fifth postoperative day without any complication .\nwandering spleen is a rarely diagnosed clinical entity . according to our knowledge less than 500 cases of patients with recurrent abdominal pain or abdominal emergency caused by a wandering spleen\nmoreover , splenectomy for treatment of a wandering spleen account for less than 0.25% of splenectomies in reported series .\nwandering spleen is 7 times more common in females than males after age 10 and 2.5 times more common in males than females under the age of 1 year .\nthe most common age of presentation is childhood especially under 1 year of age followed by the third decade of life , and is more frequently seen in females of reproductive age . wandering spleen occurs because of either extreme laxity or absence of the normal ligaments that attach the spleen to its fixed position in the left upper quadrant .\nthree of these ligaments are virtually always present ( except in the condition of the wandering spleen ) , and two may be present to variable extents .\nthe three ligaments , that are constantly present , are the splenogastric ligament , the splenorenal ligament and the splenocolic ligament .\nthe two ligaments , that are variably present , are the splenoomental and the splenophrenic ligament .\nabsence or laxity of the above mentioned ligaments allows the spleen to essentially drop to the lower abdomen in either the right or the left lower quadrant by the force of gravity attached by its elongated vascular pedicle .\nit occurs most probably as a result of congenital anomalies in the development of the dorsal mesogastrium and the absence or malformation of the normal splenic suspensory ligaments .\nconditions associated with wandering spleen include enlargement or absence of a kidney , splenomegaly and previous pregnancy .\nsplenomegaly and pregnancy are thought to contribute to the laxity of the supporting structure by direct effect of gravity and estrogen respectively .\nsymptoms may remain limited or absent for long periods of time , but complications related to torsion , compression of another organ by the spleen or its pedicle and susceptibility of the spleen to trauma are quite common .\ninitially , irreducible torsion produces venous congestion as a result of which the spleen becomes edematous and enlarged . eventually , progressive torsion results in infraction of the arterial supply , acute ischemia , strangulation , necrosis and rupture of the congested and gangrenous spleen .\nmore frequently , patients are admitted due to a non specific chronic pelvic pain related to splenomegaly or pressure on adjacent organs .\nthe most common physical finding is a palpable lower abdominal mass representing the abnormally enlarged torted spleen .\nlaboratory tests are usually nonspecific , but may occasionally reveal evidence of hypersplenism or functional asplenia .\nultrasonography , nuclear scintigraphy , ct and mri can prove useful in revealing the nature of a pelvic mass of unknown entity and confirm the diagnosis of an ectopic spleen .\noperative management is the treatment of choice in uncomplicated and complicated cases because conservative treatment of an asymptomatic wandering spleen is associated with a complication rate of 65% .\nthe wandering spleen is ideally for laparoscopic splenectomy because it is generally free from attachments and other organs .\nthe treatment for a wandering spleen as an incidental finding at laparotomy or if the torsion can be corrected and the spleen appears to be viable is splenopexy .\nsplenopexy has been successful in preventing complications of wandering spleen while preserving the splenic function .\nthey applied open or laparoscopic techniques with or without using a mesh and peritoneal flaps .\nas the torsion involves the vascular pedicle , partial splenectomy or splenic implantation of the totally strangulated spleen is usually unattainable .\nhowever , partial infraction of a wandering spleen necessitating partial splenectomy and splenopexy or splenectomy and splenic implantation has been reported in the literature .\nthe present report was referred to a patient with progressive torsion of a pelvic spleen causing recurrent abdominal pain and eventually spleen strangulation and rupture . the patient exhibited a period of vague intermittent lower abdominal pain lasted 65 days followed by a period of constant left lower quadrant pain of increasing severity lasted 6 days .\non the first 65 days , vague pain was attributed to progressive torsion which resulted in venous congestion and enlargement of the spleen . on the last 6 days ,\nexacerbation of pain was attributed to irreducible torsion , infraction of the arterial supply , acute ischemia , strangulation , necrosis and rupture of the congested and gangrenous spleen .\nalthough the presence of the ectopic spleen could be easily identifiable on serial physical examinations since childhood , it was diagnosed in adulthood due to manifestation of complications .\nwritten informed consent was obtained from the patient for publication of this case report and accompanying images .\nkonstantinos boulas , salpigktidis i and barettas n equally contributed to the writing of this paper .\nkonstantinos blouhos , anestis hatzigeorgiadis and konstantinos boulas performed the operation.key learning pointsthe presence of an ectopic spleen can be easily identified on serial physical examinations since childhood.however it is commonly misdiagnosed until the manifestation of complications in adulthood . the\npresence of an ectopic spleen can be easily identified on serial physical examinations since childhood.however it is commonly misdiagnosed until the manifestation of complications in adulthood .\nthe presence of an ectopic spleen can be easily identified on serial physical examinations since childhood .", "answer": "introductionectopic spleen is an uncommon clinical entity as splenectomy for treatment of ectopic spleens accounts for less than 0.25% of splenectomies . \n the most common age of presentation is childhood especially under 1 year of age followed by the third decade of life.presentation of casethe present report refers to a patient with torsion of a pelvic spleen treated with splenectomy . \n the patient exhibited a period of vague intermittent lower abdominal pain lasted 65 days followed by a period of constant left lower quadrant pain of increasing severity lasted 6 days . \n on the first 65 days , vague pain was attributed to progressive torsion of the spleen which resulted in venous congestion . on the last 6 days , \n exacerbation of pain was attributed to irreducible torsion , infraction of the arterial supply , acute ischemia , strangulation and rupture of the gangrenous spleen . \n diagnosis was made by ct which revealed absence of the spleen in its normal position , a homogeneous pelvic mass with no contrast enhancement , free blood in the peritoneal cavity , and confirmed by laparotomy.discussionclinical manifestations of ectopic spleen vary from asymptomatic to abdominal emergency . \n symptoms are most commonly attributed to complications related to torsion . \n operative management , including splenopexy or splenectomy , is the treatment of choice in uncomplicated and complicated cases because conservative treatment of an asymptomatic ectopic spleen is associated with a complication rate of 65%.conclusionalthough an ectopic spleen can be easily identified on clinical examination , it is commonly misdiagnosed until the manifestation of complications in adulthood .", "id": 989} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npalisaded encapsulated neuromas clinically manifest as solitary , firm , non - pigmented , dome - shaped nodules on the face of adult patients . palisaded encapsulated neuroma is known as a benign tumor of the facial skin , and is rarely found in the oral mucosa .\nmicroscopically , the tumors are characterized by moderately cellular , fascicular proliferation of spindle cells that show some areas of parallel nuclei .\na bundle of nerves interposed between the schwann cells typically aggregates in palisades and is identified by s-100 protein immunohistochemical stain .\nan alternate designation i.e. solitary circumscribed neuroma ( scn ) was proposed by fletcher in 1989 .\nirrespective of the nomenclature , pen / scns are considered as reactive hyperplastic processes . in 2010 ,\nkoutlas and scheithauer considered pen / scns as relatively common true neuromas of the skin or mucosa . as a peripheral nerve sheath tumor , pen accounts for only 0.04 to 0.05% of oral biopsy specimens .\nother peripheral nerve sheath tumors are neurofibroma , schwannoma ( neurilemmoma ) , mucosal neuroma associated with multiple endocrine neoplasia iii , nerve sheath myxoma and granular cell tumor . in the mouth , pen is mostly found on the hard palate and maxillary labial mucosa as a small , superficial and usually painless nodule .\nthe lesion is frequently diagnosed between the 5 and 7 decades of life , with equal sex predilection .\na preferred treatment for pen is conservative local surgical excision ; although gross total resection has been recently claimed to be the treatment of choice .\na 48-year - old man was referred to the oral medicine department of babol dental school , complaining of a tongue mass persisting for one year .\nphysical examination revealed an exophytic sessile mass measuring 0.3 0.4 cm with rubbery consistency on the anterior one - third of the dorsal surface of the tongue ( fig .\nclinically , the overlying mucosa was depapillated and had increased vascularity . under the impression of a pg , excision of the mass was done and no recurrence was reported at 12 months postoperatively .\nhistopathological sections showed an encapsulated mass within the connective tissue , composed of interlacing fascicles of spindle cells that were consistent with schwann cells .\nthe nuclei , showing a parallel orientation within the fascicles , were characteristically wavy and pointed , with no significant pleomorphism or mitotic activity .\nthe overlying epithelium was atrophic and no rete ridges were seen ( figs . 3 and 4 ) .\ngiemsa special stain revealed no mast cells within the stroma , ruling out the differential diagnosis of neurofibroma .\nphotomicrograph showing an encapsulated proliferation of neoplastic cells ( hematoxylin and eosin staining ; original magnification 40 ) .\nno evidence of malignancy is observed ( hematoxylin and eosin staining ; original magnification 400 ) .\nmucosal neuroma can be distinguished histologically from other neurogenic tumors such as neurofibroma , neurilemmoma and pen .\nbriefly , mucosal neuroma is not encapsulated and does not have palisading nuclei ; whereas neurofibroma and pen are encapsulated .\nmucosal neuromas are usually associated with the multiple endocrine neoplasia syndrome iii ( men iii ) , a rare syndrome with potentially fatal consequences such as medullary carcinoma of the thyroid .\nother clinical signs of the patients with men iii can be considered in the diagnosis of oral lesions such as a mucosal neuroma . however\n, when oral lesions are present in absence of other diagnostic signs , histopathological evaluation can be helpful .\nthe microscopic examination of the mucosal neuroma shows nerve bundles in various sizes surrounded by normal connective tissue , which are not usually seen in pen .\na traumatic neuroma is not a true tumor , yet it develops as a proliferation of neural tissue that is caused by injury to a peripheral nerve .\ntraumatic neuromas are usually associated with pain , ranging from pain on palpation to a constant severe pain .\nthese include the presence of perineural cells surrounding individual microfascicles , the greater abundance of interstitial collagen , mucoid matrix and myelin components , and the more orderly parallel arrangement of axons in traumatic neuroma .\nantoni a , organized spindle cells in palisaded whorls , and antoni b , haphazardly distributed neoplastic cells , are two common patterns which are often found during histopathological examination of schwannomas .\nother microscopic criteria include verocay bodies and the more definite palisading in the nuclei than that in pen .\ncontrary to the latter , it is extremely difficult to microscopically differentiate neurofibroma from pen , especially when an incisional biopsy has been performed .\nthe absence of marked fibrous capsule and the irregular arrangement of the neoplastic cells are the main differential clues seen in neurofibroma compared with pen .\nthe significant presence of mast cells , usually observed among tumoral cells of the neurofibroma , is also detectable using histochemical or immunohistochemical staining methods . as regezi and colleagues stated ,\npen / scn may be misdiagnosed clinically once identified somewhere in the mouth other than the palate .\nthis may be an obvious clinical impression since intraoral pen / scns are mostly found on the hard palate .\nconversely , the tongue involvement comprises less than 8% of pen / scn cases . as for this case\n, the pen resembled a pg on the dorsal surface of the tongue ( a common site for neurilemmoma and neurofibroma , but not for pen ) .\nan erythematous lesion in a less commonly affected site rarely happens to be a pen . besides , the tongue is a potential site for pg .\nhave reported that pg is most commonly seen on the attached gingivae , tongue , lower lip and buccal mucosa .\nthe age of patient may be an important clinical parameter when the list of differential diagnoses of a lesion is formulated .\nour patient was 48 years old , which was close to the recently reported average age for pg patients ( 52 years ) .\npyogenic granuloma usually occurs in patients older than 39 years , with equal gender distribution .\nsoft tissue enlargements of the oral cavity often present a diagnostic challenge because a diverse group of pathological processes can produce such lesions .\npyogenic granuloma can manifest as a painless smooth or lobulated mass with a surface that bleeds quite easily .\nbecause of their high level of vascularity , young pgs are red , whereas older lesions are more collagenized and appear pink or normal colored .\nclinically , oral pg occurs as an exophytic lesion manifesting as small , erythematous papule on a pedunculated or sometimes sessile base .\npyogenic granuloma arises in response to various stimuli such as chronic low - grade irritation , traumatic injury and hormonal factors .\nhowever , the effect of female hormones on oral pg was questioned by bhaskar and jacoway since they found lesions both in males and females with no sex predilection .\npalisaded encapsulated neuromas may be misdiagnosed clinically once they appear somewhere in the oral cavity other than the palate .\na pen arising on the dorsum of the tongue may mimic a pg with similar clinical morphology . even the patient s age may be misleading . on the other hand ,\nperipheral nerve sheath tumors must therefore be included in the list of differential diagnoses for a pg - like lesion on the tongue .", "answer": "palisaded encapsulated ( solitary circumscribed ) neuromas ( pens ) are relatively common intraoral neurogenic tumors , which occur most frequently on the hard palate . \n herein , we describe the clinicopathological characteristics of a palisaded encapsulated neuroma of the tongue . \n this tumor was an exophytic sessile mass measuring 0.3 0.4 cm with rubbery consistency on the anterior one - third of the dorsum of the tongue . \n the tumor was excised under the impression of a pyogenic granuloma ( pg ) . \n no recurrence was reported at 12 months postoperatively . \n histopathological examination showed a well - circumscribed mass that composed of interlacing fascicles of spindle cells . \n the cells were s-100 positive . \n the nuclei , showing parallel orientation within the fascicles , were wavy and pointed and showed no sign of mitotic activity . \n giemsa staining revealed no mast cells within the stroma .", "id": 990} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nmyxoma is a benign neoplasm of mesenchymal origin composed of undifferentiated stellate cells in a myxoid stroma , which were differentiated into altered fibroblasts and lost their ability to produce normal collagen18 ) .\nmyxoma can arise in a variety of locations ; heart , subcutaneous and aponeurotic tissues , bone , genitourinary tract and skin , etc .\nthe most frequent site for myxoma is the heart , and bony myxoma is almost exclusively limited to the jaws and palate , representing 40 - 50% of all head and neck myxomas216 ) .\nthe soft tissue myxoma is rare , and occurs mostly in the large skeletal muscles .\nthe myxomas that arise in the skeletal muscles are generally called intramuscular myxomas ( ims ) .\nthe most of ims are detected in the fourth to sixth decades of life with slight female predominance16 ) .\ni m accounts for about 3 - 17% of the all myxomas , and the incidence is about 1 case per million population per a year51823 ) . to our knowledge ,\nwe report the eighth case of a myxoma developed within the lumbosacral paraspinal muscle ( including thoracolumbar paraspinal muscle ) , which had some different characteristics from the typical i m , and brief review of the literature will be followed .\na 62-year - old female was referred to our hospital for mass - like lesion detected on magnetic resonance imaging ( mri ) of her spine .\nshe presented with low - back pain just for 3 months without radiating leg pain , and the symptom was slowly progressive .\nbut , interestingly , she had the previous history of bone harvest on the right posterior superior iliac spine ( psis ) for the cervical fusion operation 15 years ago in the other hospital . physical examination revealed a large palpable mass on the right paraspinal area in the lumbosacral region , but there was no associated tenderness in this region .\nher neurologic examination at the time of admission was fully normal , and there was no abnormal finding on the laboratory tests and the electrophysiological studies such as electromyography ( emg ) and somatosensory evoked potential ( ssep ) .\nmri demonstrated a multi - lobulated mass in the right lumbosacral paraspinal muscles in contact with the posterior elements of the l4 and l5 vertebra ( fig .\nthis well - circumscribed mass was measured approximately 4.03.56.5 cm in size , and the lesion was hypointense on t1-weighted image ( t1wi ) and hyperintense on t2-weighted image ( t2wi ) .\nthere were heterogenously enhancing foci inside the mass with peripheral and septal enhancement on the post - contrast t1wi . on computed tomography ( ct )\nscan of the lumbosacral region , this mass had low density and some calcification particularly on the inferior portion of the mass ( fig .\nthere was no bony destruction or invasion around the mass . in the process of a full diagnostic workup\n, we found her previous abdominal ct images in picture archiving computer system ( pacs ) , which had been performed for evaluation of her abdominal pain 4 months ago ( fig . 2c ,\nd ) . in the previous abdominal ct , although it was slightly smaller than the mass of recent lumbar ct , the hypodense lesion was also seen at the same area .\nit was notable that calcification inside the mass was not detected on the previous abdominal ct .\nwe planned to conduct the complete excision , instead of simple biopsy ( for example , ct - guided biopsy ) , because the tumor was not only symptomatic , but also the operation had fairly limited risk to the patient .\nthe tumor was encapsulated and lobulated with grayish white surface , and there was no evidence of the infiltration or invasion into the surrounding bony structures .\n3 ) . according to the frozen biopsy during the operation , the mass was revealed to myxoid tumor , and the final histopathological findings were consistent with intramuscular myxoma .\nthis mass was composed of prominent myxoid stroma with a distinct presence of spindle and stellate cells , and while pyknotic nuclei and karyorrhectic nuclei were also seen ( fig .\nnumerous micro - calcifications were also found , especially in the peripheral capsular area of the tumor .\nthe patient was neurologically free and experienced complete relief of her low - back pain postoperatively .\nsince stout et al18 ) . outlined the diagnostic criteria and defined myxoma at 1948 , the intramuscular myxoma has been known as the most rare sub - type in these tumor category .\nims have been reported at the various locations such as thighs , buttocks , upper limbs , shoulders , and paravertebral area . of those ims ,\nparaspinal regions are the most uncommon site , and so far , only 14 cases of paraspinal ims have been reported .\nand to the best of our knowledge , this report is just the eighth case of paraspinal i m in the lumbosacral area including one case of thoracolumbar lesion , and the first case in asian population ( table 1)891114151720 ) .\nims usually appear as well - circumscribed homogeneous low - density lesions within the skeletal muscle on ct scan , and have low - signal intensity on t1wi and high - signal intensity on t2wi .\nbancroft el al.1 ) described that the peri - tumoral fat rind on t1wi and increased signal in the adjacent muscle on t2wi are the most reliable radiologic features for distinguishing intramuscular myxoma from other myxoid tumor .\nbut in this case , this finding was not definite on the mri . on gross inspection , the tumor has usually oval shape and shows well - circumscribed appearance , however its fibrous tissue often has incomplete pseudocapsule to result in infiltration of adjacent musculature510 ) . and\nin general the tumor has a glistering gray - white appearance and contains gelatinous material and cyst filled with fluid inside the mass .\nhistologically , ims are composed of well - localized myxomatous connective tissue surrounded by a collagenous fibrous connective tissue22 ) .\nims are often confused with other pathologic conditions such as ganglion or neurofibroma , and furthermore , with other mucoid sarcomas such as liposarcomas , chondrosarcomas , low - grade fibromyxoid sarcoma and malignant histiocytomas , because these sarcomas are also accompanied by the myxomatous degeneration .\nhowever , several critical clues had been presented , which help to distinguish ims from other myxoid lesions .\nfirst , ims have poor vascularization and a paucity of cells ( lipoblasts or chondroblasts ) , in contrast to myxoid liposarcoma which has a rich , delicate , plexiform capillary vascular network . secondly , ims lack nuclear atypia , necrosis , and prominent mitotic activity .\nin addition , on the enhanced mri , soft tissue sarcomas showed heterogeneity , intense enhancement , septation , ill - defined margins and invasion of adjacent structure against the ims .\nmoreover , ims often do not have a true capsule , and therefore could infiltrate to the adjacent striated muscle , resulting in muscle atrophy which appear as a peri - tumoral fat rind on t1wi .\nadditionally , doyle et al.4 ) presented the muc4 protein as a specific marker for distinguishing from low - grade fibromyxoid sarcroma .\nims usually present as a solitary slow growing painless mass , however multiple myxomas can occur on rare specific condition , for example , mazabraud 's syndrome .\nthe clinical manifestations of ims generally are non - specific , but rather presenting symptoms depend on the affected locations . in our case ,\nthe patient also presented with ambiguous low back pain and this symptom was resolved after total resection of the tumor . in general , ims are known as slowly growing and painless tumors , whereas there are some differences from typical natures of ims in this case .\nfirst , it had been just asymptomatic mass , but it developed to symptomatic lesion in a very short time ( about 3 months ) .\nthere was demonstrable difference in size of the tumor ; widthlengthheight=3.03.05.4 cm to 4.03.56.5 cm .\nin addition , a new calcification inside the mass was accompanied with tumor growth , while there is no internal calcification in most cases of i m .\nthird , the location of i m was adjacent to the previous operation site ( iliac bone harvest site ) .\nalthough the pathogenesis of ims remains obscure , there are several theories for explaining the pathogenesis . according to one of the theories ,\nstellate cells may be altered fibroblasts that fail to produce mature collagen5 ) . by glazunov and puckov , \" viral origin \"\nwirth et al.24 ) proposed the fibrous dysplasia as another theory for the pathogenesis of ims , and fibrous dysplasia usually precedes the ims by several years .\nwe assumed that interruption of paraspinal muscles by previous operation could induce fibrous dysplasia to arise i m .\nthough there was no report about the prevalence by race due to the rarity of the incidence of ims , previous many reports were almost confined to the western population .\nour case is the first case of i m in asian people , which developed in the lumbosacral paraspinal musculature .\nthe clinical course of ims is known to be nearly benign , and the treatment for ims is the total surgical resection . there is no report of metastasis or malignant change , but occasionally local recurrence resulting from incomplete resection has been reported6913 ) .\ntherefore , if possible , wide excision with clean margins is recommended to avoid local recurrence , since ims have an infiltrative tendency to surrounding muscles .\nwe report the first case of the paraspinal intramuscular myxoma developed in the lumbosacral area in asian population .\nintramuscular myxomas are uncommon benign tumors , especially in the paraspinal area , and moreover it is difficult to make a diagnosis before operation because of the lack of characteristic clinical history and radiographic findings , however , neurosurgeons should be aware of this entity .", "answer": "intramuscular myxoma ( i m ) is a benign neoplasm of mesenchymal origin . \n we report a rare case of i m which was located in the lumbosacral paraspinal muscles . \n a 62-year - old female patient presented with progressive low back pain for 2 months , and the radiologic findings showed a large mass ( 4.03.56.5 cm ) in the right lumbosacral paraspinal area . \n total resection of the tumor was performed and the symptom was nearly resolved after surgery . although the immuno - histopathological analysis was consistent with i m , there were some different findings from typical pathological characteristics of i m in this case . \n firstly , the symptomatic change of the mass took relatively short time ( less than 3 months ) , and this change was accompanied by partial calcification inside the mass . \n moreover , iatrogenic interruption of paravertebral muscle by the other previous operation might be the promoting factor of the fibrous dysplasia , which can explain the pathogenesis of i m . \n to our knowledge , this is the eighth case of the lumbar paraspinal myxoma reported in the literatures and the first case in asian population .", "id": 991} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nperinatal depression is a major public health problem , affecting up to a quarter of all pregnant women in rural countries .\nit is associated with profound physical and emotional changes and associated risks for the onset or exacerbation of several mental disorders such as depression .\nin addition to its effects on the mother 's well - being , perinatal depression is associated with adverse outcomes of pregnancy .\nrelevant effective interventions are being developed , but their effectiveness in low- and middle - income countries may be limited by various factors .\nexercise can provide a viable treatment options for depressed patients , whether as an alternative treatment strategy to conventional treatments or as a supplemental strategy , either in the short - term or long - term .\nresearch to date by low numbers to support the use of exercise in some form as a positive treatment option for individuals suffering from depression .\nall married women aged 1740 years with low socioeconomic status in their second trimester of pregnancy , who had depression , were considered .\nwomen with a diagnosed medical condition , pregnancy - related illness , significant physical or intellectual disability , post par tumor other form of psychosis , and severe depressions were excluded . during the pre - intervention assessment ,\nboth groups were asked to attend post - intervention assessment 4 and 8 weeks following the start of the program to complete the questionnaire .\nsubjects in this group had 4 weeks exercise program , cycle 4 sessions a week for 4060 min / session .\nthe exercise in each session were including : 10 min heating with walking , stretching and flexibility , and three sets of moderate intensity cycling in 6 min with 6065% of maximum heart rate .\nsubjects in the control group were given a patient handout which is in gujarati explaining about the procedures to do as home based program .\nthe hand out consist of five criteria such as stay active , do something that you think is fun each day , spend time with people who help or support you , relaxing and set simple goals .\ninter group analysis was done using wilcoxon - mann whitney test and intra group analysis was done using one - way anova .\nduring the pre - intervention assessment , subjects have undergone kuppuswamy 's socioeconomic status scale and the physical health questionnaire-9 .\nboth groups were asked to attend post - intervention assessment 4 and 8 weeks following the start of the program to complete the questionnaire .\nsubjects in this group had 4 weeks exercise program , cycle 4 sessions a week for 4060 min / session .\nthe exercise in each session were including : 10 min heating with walking , stretching and flexibility , and three sets of moderate intensity cycling in 6 min with 6065% of maximum heart rate .\nsubjects in the control group were given a patient handout which is in gujarati explaining about the procedures to do as home based program .\nthe hand out consist of five criteria such as stay active , do something that you think is fun each day , spend time with people who help or support you , relaxing and set simple goals .\ninter group analysis was done using wilcoxon - mann whitney test and intra group analysis was done using one - way anova .\nof 146 subjects , 80 ( 55% ) met the inclusion criteria and 60 ( 41% ) agreed to enroll .\nfour subjects were excluded from the analysis in the exercise group ( group 1 ) and 2 subjects were excluded from analysis in the control group ( group 2 ) .\nno significance differences between groups were found at baseline on outcome variable such as depression level .\nanalysis of depression level shows significant changes within and between exercise and control group . at baseline , the mean depression score was 15.96 ( 3.09 ) and 16.23 ( 3.38 ) for the exercise group and the control group , respectively . after the 4-weeks intervention ,\nthe mean score fell to 6.10 ( 2.44 ) for the exercise group ( 43.54% ) and to 10.60 ( 2.74 ) for the control group ( 21.25% ) .\nat the 8 weeks follow - up , the mean score was 1.34 ( 1.09 ) for the exercise group ( 72.81% ) and 5.03 ( 1.50 ) for the control group ( 42.50% ) .\nexercise has been shown in a number of studies to prove beneficial in the treatment of depressive symptoms especially in perinatal and post natal conditions .\nbartholomew showed that a single incidence of exercise can have a positive effect on mood . maintaining the intensity and frequency of exercise recommended by most public health agencies were sufficient to provide a significant reduction in major depressive disorder ( mdd ) symptoms .\nthe additional benefits of exercise to individuals suffering from depression include stress reduction , better attitude , improved outlook , self - confidence , and mental well - being .\nour intervention , the physical exercises was developed to provide a culturally appropriate , feasible , and evidence - based physical therapy intervention for women living in very poor communities in rural india .\nthese results suggest that supervised physical exercise provides better improvement in depression status in perinatal subjects .", "answer": "background : perinatal depression is a major public health problem , affecting up to a quarter of all pregnant women in rural asean countries and often leads to psychologic symptoms , lower quality of life , and higher health care costs . the purpose of this study was to assess the impact of supervised physical exercise on depression level of perinatal subjects.subjects/intervention:60 subjects who fulfill the selection criteria were randomly assigned to exercise ( group-1 , n=30 ) and control group ( group-2 , n=30 ) . \n participants completed general screening form and physical health questionnaire-9 ( phq-9 ) before their intervention and again 4 weeks and 8 weeks later . \n group-1 underwent aerobic training with 60 - 65% maximum heart rate and group-2 was prescribed with handouts for 4 weeks.statistics:repeated-measures analysis of variance ( anova ) was use to analyze group differences over time while controlling for baseline differences.results:demographic and the baseline values show homogenous population ( p>0.05 ) . \n patients in both groups experienced significant reduction in depression level . \n group a showed reduction of 91.70% ( p=0.00 ) as compared to group b 69.01% ( p=0.00).conclusion : these results suggest that supervised physical exercise provides better improvement in depression status in perinatal subjects than providing handouts alone .", "id": 992} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe need for categorization of anomalies and congenital aberrancies formed due to developmental vascular defects produce identifiable birthmarks of the skin and mucosa and a variable degree of underlying soft tissue abnormalities .\npresently a surge in the knowledge of criterias to classify these various anomalies has put forth classifications purely with respect to histopathological features of the disease .\nthese lesions predominantly occur within the head and neck and affect approximately 1 in 22 children .\ninvolvement of the oral cavity is common but frequently requires unconventional treatment strategies for its management .\nthough previously termed angiomas or vascular birthmarks , vascular anomalies are divided into two main categories : vascular tumors and vascular malformations .\ninfantile hemangiomas comprise the majority of vascular anomalies and are considered the predominant vascular tumor type composed of rapidly proliferating endothelial cells .\nblood vessel architecture is incomplete and surrounded by hyperplastic cells in hemangiomas and other vascular tumors . in contrast , vascular malformations do not contain hyperplastic cells but consist of progressively enlarging aberrant and ectatic vessels composed of a particular vascular architecture such as veins , lymphatic vessels , venules , capillaries , arteries or mixed vessel type .\nthe latter comprises lymphangiomas or lymphatic malformations which are congenital collections of ectatic lymph vessels that form endothelial lined cystic spaces .\nthe pathogenesis of these tumors could be of importance in thoroughly understanding the mode of these varying histopathological presentations .\nthey represent about 6% of the total number of benign tumors of the soft tissue in patients aged less than 20 years .\nregarding gender distribution of lymphangioma , it is equally divided between males and females , with about 50% of the lesions being noted at birth and 90% developing by 2 years of age .\noral lesions may occur at various sites but they form most frequently on the anterior two thirds of tongue\n. they may increase in size , producing macroglossia which may lead to difficulties in mastication , deglutition , and speech ; and displacement of the teeth , with a resulting malocclusion .\nthey may interfere with normal breathing , particularly during sleep , produce sleep apnea , and in certain instances , produce a life - threatening upper airway compromise .\nthey can also be present in the palate , buccal mucosa , gingiva and lip .\nthe tumor is superficial in location and demonstrates a white pebbly surface that resembles a cluster of translucent vesicles . the deeper lesions could mimic various soft tissue tumors since the color which is classically used for diagnosing such tumors would seem to be irrelevant .\nthey appear as a nodule or masses without significant change in surface texture or color .\na 9-year - old female patient reported to the department of oral & maxillofacial pathology , i.t.s cdsr , with a complaint of a painless growth with respect to left side of tongue .\npatient had given a history of trauma due to tongue bite around 3 months back and was enlarging slowly in size the swelling was initially small , peanut sized , which increased to the present size .\non examination of the swelling a growth of 2 1 cm on the anterior part of the dorsal surface of tongue .\nthe lesion was pale pink in color and oval in shape with well - defined margins [ figure 1 ] .\nintraoral photograph showing nodular swelling resembling cluster of vesicles on the left side of dorsum of tongue an incisional biopsy was performed and the tissue was histopathologically diagnosed as lymphangioma , since large lymphatic vessels lined by flattened endothelial cells pushing into the overlying epithelium were seen [ figure 2 ] .\npatient was recalled after 4 days and a total excision of the lesion was performed under local anesthesia ( la ) .\nphotomicrograph of incisional biopsy showing large lymphatic vessels ( h and e , 10 ) examination of gross macroscopic appearance revealed the excised tissue to be oval shaped , measuring 1.5 1 cm in size and was creamish brown in color with a pebbly surface .\nmicroscopic examination of the excised lesion showed numerous large , dilated lymphatic channels of irregular shape , lined by flattened endothelial cells , of which some of the vessels were filled with lymph .\nnumerous large- to medium - sized channels with thin endothelial lining , engorged with rbcs , were also present in the deeper area of the connective tissue [ figure 3 , inset ] .\nlymphangioma was first described by virchow in 1854 , and in 1872 , krester hypothesized that hygromas were derived from lymphatic tissue .\nthe origin of lesion is considered to be congenital abnormality of lymphatic system rather than true neoplasm .\na portion of the jugular lymphatic sac is thought to sequestrate from the primary sacs during fetal development with failure to establish communications with other lymphatic system .\nthe fact that most lymphangiomas manifest clinically during early childhood and develop in areas where the primitive lymph sacs occur ( neck , axilla ) provides presumptive evidence for this hypothesis . on the contrary\n, it is argued that instead of being a congenital malformation , lymphangioma is a true neoplasm resulting from transformed lymphatic endothelial cells and/or stromal cells .\nthe classic sequence of events in embryology and development of vasculogenesis falls into three stages : the undifferentiated capillary network stage , the retiform developmental stage and the final developmental stage .\nthe first theory is that the lymphatic system develops from five primitive sacs arising from venous system .\nconcerning the head and neck , endothelial outpouchings from the jugular sacs spread centrifugally to form the lymphatic systems .\nanother theory proposes that the lymphatic system develops from mesenchymal clefts in the venous plexus reticulum and spreads centripetally toward the jugular sacs .\nseveral studies have been published regarding possible lymphangiogenic growth factor involvement in the etiology of lymphatic malformations .\nthese factors include vascular endothelial growth factor ( vegf)-c , vascular endothelial growth factor receptor 3 ( vegfr-3 ) , and transcription factor prox-1 .\nvegf - c and vegfr-3 have been shown to be upregulated in lymphatic malformed tissue , and both are involved in lymphatic tissue proliferation .\nthe tumor may be localized in a small area of tongue or floor of mouth or it may diffusely infiltrate these areas . if the tumor is located in a deeper area , it may present as submucosal mass .\ncervical lesions in a child cause dysphagia and airway obstruction which is rare in adults .\nthe misunderstanding on the nosologic distinction between oral hemangiomas and vascular malformations leads to diagnostic mistakes .\nhemangiomas are differentiated from vascular malformations by their clinical appearance , histopathological features , and biologic features\n. the natural history of hemangiomas involves rapid proliferations for the first several months of life with subsequent spontaneous regression .\nvascular malformations are often recognized at birth and grow proportionately with the child , with many becoming more prominent at puberty .\nhistologically , hemangiomas in the proliferating phase show endothelial hyperplasia and large number of mast cells .\nin contrast , vascular malformations show normal number of mast cells , and consist of mature , often combined , capillary , arterial , venous , and lymphatic elements .\nlymphatic malformations / lymphangiomas are classified microscopically into four categories : lymphangioma simplex ( lymphangioma circumscriptum ) composed of small , thin - walled lymphatics ; cavernous lymphangioma comprising dilated lymphatic vessels with surrounding adventitia ; cystic lymphangioma ( cystic hygroma ) consisting of huge , macroscopic lymphatic spaces with surrounding fibrovascular tissues and smooth muscle ; and benign lymphangioendothelioma ( acquired progressive lymphangioma ) , in which lymphatic channel dissects through dense collagen bundles .\noccasionally , channels may be filled with blood , a mixed hemangiolymphangioma , an uncommon developmental anomaly with a propensity to invade underlying tissues and to recur locally , distinguishing it from the simple lymphangioma or hemangioma .\nalthough histologically it is a benign disorder , local invasion into the muscle , bone , and underlying tissue can lead to severe deformity . in the present case ,\nnumerous large - sized lymphatic channels along with medium- to large - sized channels entrapped with rbcs , lined by endothelium , were seen and hence it was subcategorized as hemangiolymphangioma .\nwe reviewed the archival cases of lymphatic malformations in our department , the demographical information , location and histopathological features of which are shown in table 1 .\nthe only significant difference in the three archival cases and the present case was in the histopathological features of lymphangioma and hemangiolymphangioma .\nthe demographic information , location and histopathological features these anomalies present the necessity for sound discretion with regards to their approach therapeutically.although spontaneous regression of lesions is rarely encountered , the treatment seems to weigh heavily on individual assessments of the observer .\nsclerosing agents are ineffective , probably as a result of the discontinuous basement membrane of the lymphatic vessels .\nnd - yag laser surgery has been widely preferred because of its advantages of less bleeding and edema .\ndue to a rate of recurrence of nearly 21% , long - term follow - up is essential of these tumorigenic anomalies .\nthe vascular lesions consist of both blood vessels and lymphatic vessels . whether these can be termed as hemangiolymphangioma or just vascular malformation is still confusing .\nthus through the present article we would like to highlight the complexities which can arise from the terminal categorization of the large group of tumors called vascular neoplasms when based on their histopathological representation .\nfurther detailed analysis of a larger case series would be imperative in the correct classification and diagnosis which could enormously help to accurately ascertain prognosis and direct treatment .", "answer": "malformations of vascular nature originate as anomalies caused due to errors in vasculogenesis . \n these tumors are generally broadly classified into vascular tumors ( hemangiomas ) and vascular malformations ( venous malformations , arteriovenous malformations , lymphatic malformations ) . \n these descriptive tumors and malformations have been categorized based on the architectural assembly of vessels . \n lymphangiomas are further subclassified microscopically into capillary , cavernous , cystic and lymphangioendothelioma , depending upon their histopathological features . \n lymphatic malformations or lymphangiomas are uncommon congenital malformations of the lymphatic system , usually occurring in the head and neck region , characterized by collections of ectatic lymph vessels that form endothelial lined cystic spaces . \n advancements in the knowledge of pathogenesis of such vascular malformations are continuously changing their treatment protocols . \n early recognition is of utmost importance for initiation of proper treatment and avoiding serious complications . \n hemangiolymphangioma is a variant of lymphangioma showing vascular component . \n herewith , we present a case of vascular malformation diagnosed as hemangiolymphangioma histopathologically in a 9-year - old girl , along with a review of literature regarding its categorization .", "id": 993} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nfemale genital tuberculosis ( fgtb ) is common in developing countries and associated with significant morbidity in the form of menstrual dysfunction , infertility , tubal block , peritubal adhesions , intrauterine adhesions , and perihepatic adhesions .\nfallopian tubes are involved in about 90% of the cases with findings such as congested tubes , tubercles , or caseous nodules on them , peritubal adhesions , and tubal blockage at various levels such as cornual block , mid - tubal block , multiple tubal blocks , or fimbrial block , hydrosalpinx , pyosalpinx , and tubo - ovarian masses .\na 25-year - old woman with family history of pulmonary tb was presented to the gynecology outpatient department with primary infertility and oligomenorrhea of 3 years . on examination ,\nvaginal examination demonstrated anteverted uterus with fullness and induration in both fornices . on investigations ,\nhysterosalpingogram which was already performed by the referring doctor for infertility before diagnosis of fgtb was made showed bilateral tubal block .\nendometrial aspirate performed in premenstrual phase showed positive polymerase chain reaction based on the amplification of the 240 bp region of the mpt 64 gene using primers mpt 1 ( 59-tccgctgccagtcgtcttcc-39 ; nt 460479 ) and mpt 2 ( 59-gtcctcgcgag tctaggcca-39 ; nt 700681 ) with equipment using amplitron thermocycler ( barnstead / thermolyne ) , it also tested positive for culture for mycobacterium tuberculosis using mycobacterium growth indicator tube-960 .\n, there were findings of tb in the pelvis in the form of multiple tubercles on tubes and uterus , bilateral hydrosalpinx with beading of tubes , and few caseous nodules .\nwhen methylene blue dye was injected in the uterus , the fallopian tubes became distended and blue colored with beading looking with alternate constrictions and dilatation looking - like blue pythons \ndiagnosis of genital tb was made , and she was started on anti - tb therapy .\nher postoperative period and follow - up were uneventful . left fallopian tube with distension , multiple ballooning , and blue coloration with fimbrial block showing blue python sign \nalthough gold standard in diagnosis of fgtb is demonstration of mycobacterium tuberculosis either on microscopy or culture of endometrial biopsy or presence of epithelioid granuloma on histopathology , they are positive in only few cases leading on to missing of diagnosis in many cases . polymerase chain reaction on endometrial biopsy is a sensitive and rapid method for detecting mycobacterium dna ( mpt 64 gene ) but can be false positive and may not be able to differentiate between infection and disease .\ngene xpert has recently been introduced in both pulmonary and extra - pulmonary tb as a sensitive and specific method , but its data in fgtb are very sparse . imaging modalities such as ultrasound , computed tomography scan , magnetic resonance imaging , and positron emission tomography scan have main role in tubo - ovarian masses .\nhysterosalpingography is generally avoided in a suspected case of fgtb due to risk of flare up of the disease but may demonstrate tubal block and other tubal patterns , especially in advanced case .\nhysteroscopy is useful in endometrial disease and may show pale looking endometrium with endometrial cavity being partially or completely obliterated by adhesions of varying grade ( asherman 's syndrome ) which may involve ostia .\nhowever , laparoscopy is the most reliable tool to diagnose fgtb , especially for tubal , ovarian , and peritoneal disease .\nthere can be tubercles on peritoneum or tubes , tubo - ovarian masses , caseous nodules , encysted ascites , various grades of pelvic adhesions , hydrosalpinx , pyosalpinx , beaded tubes , tobacco pouch appearance , and inability to see tubes due to adhesions .\nother authors have also found laparoscopy very useful in diagnosis and management of genital and peritoneal tb with the advantage of avoidance of laparoscopy which is more traumatic and hazardous especially in a case of abdominopelvic tb . in a case of fgtb ,\nif there is no cornual block , there is a partial or complete fimbrial block with multiple blocks at various parts of tube as is typical of fgtb , dye enters the tube but remains in various parts of tubes with alternate dilatation and constriction making the tube look like a blue python as happened in the present case .\nthe new sign case is easily diagnosed by gynecologists during routine laparotomy performed for infertility patients with suspected fgtb and can aid in its diagnosis", "answer": "female genital tuberculosis ( fgtb ) is an important cause of infertility in developing countries . \n various type of tb salpingitis can be endosalpingitis , exosalpingitis , interstitial tb salpingitis , and salpingitis isthmica nodosa . \n the fallopian tubes are thickened enlarged and tortuous . \n unilateral or bilateral hydrosalpinx or pyosalpinx may be formed . \n a new sign python sign is presented in which fallopian tube looks like a blue python on dye testing in fgtb .", "id": 994} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nolfactory neuroblastoma or esthesioneuroblastoma is a rare malignant neoplasm of neuroectodermal origin arising from olfactory membrane of the sinonasal tract .\nit was originally described in french literature by berger et al . in 1924 who coined the term\nthe various synonyms used for this entity are olfactory esthesio - neuroepithelioma , esthesio - neurocytoma , esthesio - neuroepithelioma , esthesio - neuroblastoma , olfactory neuroblastoma and olfactory placode tumor . the first case in american literature\nthis tumor has broad histologic spectrum and is often histologically confused with peripheral neural ectodermal tumors and is notorious for its wide clinical behaviors .\nthe common clinical symptoms include nasal obstruction , recurrent epistaxis , hyposomia , rhinorrhea , headache and visual disturbances .\nhere we report a rare case of esthesioneuroblastoma in a female with presenting symptom as tooth pain .\na 50-year - old female reported to the department of oral medicine with the complaint of pain in the left side of the upper jaw since seven months , which was spontaneous , dull and reduced on taking analgesics .\nshe visited a general dentist five months ago and maxillary left second molar was extracted as it was considered as the causative tooth for pain , however , the patient did not get relief and the pain continued .\nshe noticed swelling of left side of the face , which gradually increased in size and there was a concomitant decrease in size of her left eye opening and the eyeball was pushing superiorly since two months .\nher medical and family history was noncontributory and upon general physical examination , all her vital signs were within normal limits .\non extraoral examination , a diffuse swelling was seen on the left maxillary area extending from infraorbital margin to mid of the cheek supero - inferiorly and ala of nose to outer canthus of eye antero - posteriorly , which was soft in consistency and tender on palpation [ figure 1a ] .\nintraorally , swelling was evident on palpation extending from maxillary tuberosity to the vestibule causing vestibular obliteration till the posterior aspect , which was tender and soft in consistency on palpation [ figure 1b ] . clinical photograph showing swelling on maxillary region and decrease in the size of the left eye ( a ) .\nintraorally , vestibular obliteration was evident ( b ) on the basis of history and clinical examination , a provisional diagnosis of malignant neoplasm of maxillary sinus was considered .\nthe coronal ct revealed a large mass originating in left maxillary sinus with destruction of its medial , superior and postero - lateral wall .\nmedially , this mass was extending into left nasal fossa leading to marked luminal compromise on the left side and superiorly extension into left orbit was noticed .\nposteriorly it was extending into infra - temporal fossa , left masseteric space and left pterygomaxillary fissure .\npartial erosion of anterior maxillary wall , hard palate and lateral pterygoid plate on left side and extension of this mass from lateral maxillary wall into left cheek was also noticed [ figure 2a and b ] .\ncoronal computed tomographic scan showing extension of lesion into sinus and nasal fossa incisional biopsy was performed and on histopathological examination , hematoxylin and eosin stain showed basophilic cells arranged in large lobar sheets with intertwining connective tissue septa .\ncells had large round nucleus with minimal pleomorphism and a thin rim of cytoplasm . pronounced vascularity and formation of pseudorosettes ( homer - wright type ) were seen in some areas , suggestive of esthesioneuroblastoma [ figure 3a and b ] .\nimmunohistochemistry revealed strongly positive neuron - specific enolase among the tumor cells and s-100 showed weak association [ figure 4a and b ] .\nso based on clinical examination and the investigations performed , a final diagnosis of esthesioneuroblastoma was given .\nthe case was referred to the oncology institute for the management and the patient was started with chemotherapy , cisplatin 50 mg ( per day ) and 5 fluorouracil 1 mg ( per day ) , and recalled after 15 days ; there was improvement in the symptoms after which the patient was lost to follow up .\nphotomicrograph showing cells arranged in sheets and intervening connective tissue stroma ( a ) ( h&e stain , 40 ) .\nphotomicrograph showing cells with large round nucleus , thin rim of cytoplasm arranged in large sheets with intertwining connective tissue septa and formation of pseudorosettes ( homer - wright type ) ( b ) ( h&e stain , 100 ) immunohistochemistry showing strongly positive neuronspecific enolase among the tumor cells ( a ) ( ihc stain , 200 ) and weak association with s-100 protein ( b ) ( ihc stain , 200 )\nesthesioneuroblastoma is a rare malignant tumor arising from olfactory epithelium and its neural origin was established by trojanowaski et al . in 1982 who demonstrated the presence of neurofilament proteins ( nfp ) in the tumor cells .\nthough , it has been reported in patients as young as two years to 90 years , a bimodal age distribution has been noted in the second and sixth decades of life .\nthere are no known etiologic agents for human olfactory neuroblastoma , however , injection of diethylnitrosamine in syrian hamsters and n - nitrosopiperidine in rats has produced tumors histologically identical to human olfactory neuroblastoma .\nthe common symptoms associated are unilateral nasal obstruction ( 70% ) and epistaxis ( 46% ) , and less common manifestations are anosmia , headache , pain , excessive lacrimation and ocular disturbances . in the present case ,\nthe patient complained of pain in left maxillary molar teeth , which is a rare symptom and also , there was decrease in size of left eye , which may be due to superior extension of tumor in the left orbit .\nthe most common site of origin is in the upper nasal cavity in the region of the cribriform plate ; other primary sites such as maxillary sinus and nasopharynx have also been reported .\nesthesioneuroblastoma is generally believed to be derived from the neurosensory receptor cells of olfactory mucosa .\nother sources of origin suggested include sphenopalatine ganglion by escat , organ of jacobson , ganglion of luci by martin et al . and olfactory placode .\nthe tumor in the present case was seen to arise from left maxillary sinus and extended to involve nasal fossa , infra - temporal fossa , masseteric space , cheek and the left orbit .\naccording to this classification , stage a tumors are confined to the nasal cavity , stage b tumors have paranasal sinus extension and stage c tumors have extra - paranasal extension including the involvement of the cribriform plate , base of skull , orbit or intracranial cavity .\nthis classification was modified by morita et al . in 1993 who established stage d in the classification for tumors with metastasis to cervical lymph nodes or distant site .\nkadish 's classification has been used by various authors and appears to correlate well with the clinical outcome .\nthe present case can be categorized as belonging to stage c of kadish 's classification . in evaluation of esthesioneuroblastoma ,\nthe extent of disease is best determined by pre- and post - contrast mr imaging in which there is intense signal in t2-weighted images with marked enhancement of t1-weighted images after gadolinium injection .\ndetails of bone erosion ( lamina papyracea , cribriform plate and fovea ethmoidalis ) are better demonstrated by ct scan .\ntumor is presented as homogenous density mass , equal or greater to the surrounding soft tissue and no tumor cysts or calcifications .\ncoronal images were of value in evaluating extension to the orbit and through the cribriform plate and the anterior cranial fossa .\n( 2001 ) demonstrated the usefulness of technetinium-99m - ethyl cysteinate dimer ( tc - ecd ) spect in detection of olfactory neuroblastoma .\n( 1960 ) stated that the characteristic histologic features of olfactory neuroblastoma are plexiform intercellular fibrils , round - to - oval - shaped nuclei with scanty cytoplasm , distinct and sharply defined chromatin , which may be coarse or fine , compartmentation of sheets of neoplastic cells into lobules by slender vascular fibrous septa , true neural rosettes ( flexner - wintersteiner type ) and pseudorosettes ( homer - wright type ) .\nthey concluded that if fibrils were absent , then the tumor can not be classified as neuroblastoma with certainity .\nhistologically neuroblastoma has been classified as olfactory neurocytoma ( pattern i of mendeloff ) , a tumor with a sheet of round small cells separated by connective tissue septa and occasionally pseudorosettes ; olfactory neuroepithelioma ( pattern ii of mendeloff ) , a tumor containing round to oval nuclei clear nuclear membrane , scant cytoplasm and rosettes ; and a tumor similar to neuroblastomas found elsewhere in the body .\nimmunologically , it is most reactive with neuron - specific enolase ( nse ) as seen in the reported case .\nit has shown reactivity with s-100 , synaptophysin , nfp , class iii beta - tubulin and microtubule - associated protein .\nlight microscopy can usually establish the diagnosis , but highly undifferentiated tumors make this difficult . in case when light microscopy fails to establish diagnosis , electron microscopy is helpful .\nesthesioneuroblastoma must be distinguished from lymphosarcoma , transitional cell carcinoma , plasmacytoma , reticulum cell carcinoma , small cell undifferentiated carcinoma and ewing 's sarcoma .\nsmall cell carcinoma typically is a submucosal hypercellular proliferation growing in sheets , cords and ribbons ; the distinct lobular pattern of olfactory neuroblastoma is absent .\nthe cells are small and hyperchromatic with oval- to spindle - shaped nuclei , absent nucleoli and minimal cytoplasm .\nalthough uncommon , neural - type rosettes similar to those seen in olfactory neuroblastoma can be seen in association with small cell carcinoma .\nin contrast to olfactory neuroblastoma , nse reactivity in small cell carcinoma is more likely to be focal than diffusely positive and the s-100 protein staining , if present , is dispersed throughout the cellular proliferation and not limited to sustentacular cells .\newing 's sarcoma is composed of solid sheets or masses of solid round cells with very little stroma , scanty cytoplasm and ovoid large nuclei ; necrosis is common .\nthe characteristic cells of plasmacytoma and so - called cylinders in cylindromas readily help in identifying these tumors .\nsmall cell undifferentiated carcinomas does not contain fibrils and the distinct cytoplasmic borders can be seen .\nthe current accepted standard of treatment is craniofacial resection followed by adjuvant radiotherapy to a dose of 55 - 65 gy for kadish stages b and c. small kadish stage a disease is treated by surgery alone in some situations by some groups , but most suggest adjuvant radiotherapy for these lesions also .\nneoadjuvant chemotherapy has been used in advanced disease and where complete resection is not possible , with cyclophosphamide , vincristine ifosphamide , etoposide and cisplatin combined with preoperative radiotherapy .\nthe overall five , 10 and 15-year survival rates have been reported to be 78% , 71% and 68% , respectively .\ninitial multimodality therapy is associated with five - year survival of 80% for low - grade tumors and 40% for high - grade tumors .\nthe most hazardous and often fatal complication is intracranial extension of tumor through destruction of cribriform plate and orbital plates and secondly due to distant metastasis .\nprognosis has been correlated to clinical staging with five - year survival of 75 - 91% , 68 - 71% and 41 - 47% for stages\nother factors that have been implicated in prognosis include histologic grading , proliferation rate and ploidy .\nhistologically lower grade tumors ( grades i and ii ) have been reported to have a better five - year survival than higher grade tumors ( grades iii and iv ) .\nthe tumor metastasizes widely by both hematogenous and lymphatic routes , approximately 10 - 60% will experience distant metastasis .\nthe most common site for metastasis spread are cervical lymph nodes , and less frequent are lungs , brain , bone , spinal column , breast and abdominal viscera .\nmetastasis to the central nervous system is infrequent and in spinal cord 80% of metastasis is in cauda equine .\n, this tumor has been difficult to recognize and diagnose pathologically and the wide spectrum of presentation of this tumor has resulted in its frequent misdiagnosis .\nthus , the diagnosis of esthesioneuroblastoma demands a specialized and experienced head and neck pathologist , especially as incidence rate is low . also , esthesioneuroblastoma may present , only as tooth pain as in the present case .\nso , it may be considered as a possible differential diagnosis , though rare in cases of dento - facial pain of idiopathic cause .", "answer": "esthesioneuroblastoma , also called olfactory neuroblastoma , is a rare malignant tumor originating in the olfactory epithelium in the upper nasal cavity with intracranial extension and may also be associated with secondary sinus diseases . \n esthesioneuroblastoma has been observed to cause death by distant metastasis or by invasion through the cribriform plate and secondary meningitis . \n it usually produces nasal obstruction , epistaxis and less commonly anosmia , headache and pain . \n we report a case of esthesioneuroblastoma in a 50-year - old female who reported with tooth pain as a presenting symptom .", "id": 995} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\npyomyositis affects the massive skeletal muscles and is most frequently caused by staphylococcus bacteria ( 1 ) .\nnecrotizing fasciitis is a localized spread of infection that follows events such as trauma or surgery ( 2 ) , and which is commonly affected by group a streptococcus .\nrhabdomyolysis comprehensively affects the skeletal muscle and , like pyomyositis and necrotizing faciitis , shows serum creatinine kinase elevation ; however , rhabdomyolysis occurs as a systemic disease and is not associated with the focal manifestation of abscesses ( 3 ) .\nthe pathogenesis of infectious rhabdomyolysis is thought to be associated with the systemic or local metabolic changes related to a systemic or local infection ( 4 ) ; however , the mechanisms underlying its pathogenesis have not been established . in addition , gram - negative bacillus rhabdomyolysis is rare , and its microbiological pathology remains to be elucidated .\nwe diagnosed the patient , a 64-year - old japanese man with multiple myeloma , with bacteremia caused by morganella morganii .\nhe was admitted to our institute due to septic shock at the sudden onset of a febrile episode .\nhis vital signs at admission were as follows : blood pressure , 82/60 mmhg ; heart rate , 78/min ; body temperature , 39.1 ; respiration rate , 20/min ; and spo2 , 95% ( room air ) .\nthe laboratory findings at the time of his diagnosis showed massive myolysis and a significantly elevated level of creatinine kinase ( ck ; 3,582 u / l ) ; thereafter , an isotype analysis of the patient 's ck confirmed that the elevated ck was derived from the patient 's skeletal muscle ( 98.8% ) .\nthe status of the patient 's multiple myeloma , which had been diagnosed 5 years earlier , was stage iiia , igg type .\nhe had undergone treatment with a variety of chemotherapies : melphalan ( mp ; 12 mg / day for 4 days + prednisolone 60 mg / day for 6 days , repeated triweekly ) , vad ( vincristine 0.4 mg / m for 4 days as a continuous infusion + doxorubicin 10 mg / m for 4 days as a continuous infusion + dexamethasone 40 mg / day , days 1 - 4 , 9 - 12 , and 17 - 20 , repeated monthly ) , bd ( bortezomib 1.3 mg / m on days 1 , 4 , 8 , and 11 + dexamethasone 40 mg / day for 4 days , repeated monthly ) , and thalidomide ( 100 mg / day ) .\nhis last treatments were lenalidomide 20 mg / day , and igg gradually increased 6 months before the current infectious episode .\nafter the patient 's admission for sepsis caused by m. morganii , rehydration was immediately performed via central venous catheterization and a catecholamine infusion ( dopamine 3 mg / kg / h ) was administered ; at the same time , antimicrobial treatment with meropenem ( 0.5 g three times a day ) was initiated .\ncervical to pelvis computed tomography ( ct ) was performed on the day of admission , but there were no clear findings explaining the patient 's massive myolysis . on day 2 of the patient 's hospitalization ,\nthe patient 's vital sign were as follows : blood pressure , 61/45 mmhg ; heart rate , 87/min ; and body temperature , 36.8. we started hemodialysis combined with endotoxin absorption the same day .\nhowever , respiratory failure occurred , necessitating mechanical ventilation , on the night of day 2 .\nthe patient died of multi - organ failure two days after undergoing intubation . before his death , rhabdomyolysis developed day - by - day and was reflected in the remarkable elevation of the patient 's ck level .\nthe final ck value was 19,790 u / l ( normal range : 40 - 200 u / l ) ( figure ) .\nwe found that the m. morganii was sensitive to all of the broad spectrum beta - lactams , including carbapenems and cephalosporins , but only resistant to cefotiam , minomycin , and ciprofloxacin .\nhis muscle damage manifested as with elevated levels of ck , aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , and lactate dehydrogenase ( ldh ) after the onset of the disease ( day 1 ) , with increasing leukocytes and c - reactive protein ( crp ) .\nthe days in the x - axis indicate the days after the patient s admission .\nthe patient visited our outpatient clinic for a routine follow - up examination 6 days before his admission .\ninfectious rhabdomyolysis is caused by various pathogens including viruses , bacteria and fungi ( 3 ) .\nthe clinical entity of infectious rhabdomyolysis was established in 1982 ( 5 ) , and a review ( 3 ) identified the predisposing risk factors for rhabdomyolysis : alcohol ingestion , compression injury , and generalized seizures . regardless of the pathogen that causes infectious rhabdomyolysis , the underlying mechanism of the disease is metabolic .\nthe most frequent differential diagnosis is necrotizing fasciitis , which occurs when the infection spreads into the deep fascial layers ( 2 ) .\nnecrotizing fasciitis is generally caused by infection , and the initial entry site is sometimes trivial . in contrast\n, rhabdomyolysis is caused by the following two critical conditions : ( 1 ) physical distress ( for example , distress due to or involving excessive exercise , seizure , muscle compression , hyperthermia , or hypothermia ) ; and ( 2 ) systemic metabolic disorders ( for example disorders due to hypoxia , acidemia , drug abuse , infection , or inflammation ) .\nthe localization of a soft - tissue infection can be distinguished by systemic imaging , especially by sensitive mri ( 6 ) . in the reported cases of rhabdomyolysis , the local radiological findings are faint . in the present case ,\nour evaluation of the present case raised an important question : what is the microbiological mechanism underlying the development of rhabdomyolysis accompanied by systemic infection ( 3,7 ) ?\nthus , rhabdomyolysis is relatively common among patients with miscellaneous bacterial infections including , but not limited to , legionella ( 4 ) , pneumococcal ( 8) , and salmonella ( 7 ) .\nwe underscore that patients these types of infectious rhabdomyolysis share the following common findings : 1 ) the patients were immunocompromised due to malignancy or a severe wound ; 2 ) precedent or concomitant acute renal failure were observed in the patient 's clinical course ; and 3 ) metabolic abnormalities such as dehydration or acidemia due to single / multi - organ failure existed as the underlying pathogenesis .\nthus , ischemia or hypoxia caused by systemic infection are considered to be involved in the mechanism underlying the development of rhabdomyolysis .\nm. morganii is rarely pathogenic in humans , but it sometimes develops into an opportunistic infection in a compromised host . although there are no reported cases of infectious rhabdomyolysis caused by m. morganii , arranz - caso et al .\nthe authors noted that gram - negative bacterial pyomyositis can occur in an immunocompromised case followed by enteric organism translocation .\ngram - negative bacterial infection does not favor pyomyositis , which is usually raised by gram - positive bacteria .\nour case suggests that infectious rhabdomyolysis may be underdiagnosed as a comorbidity of gram - negative bacterial infections , even if the causative organism is an opportunistic pathogen such as m. morganii . regarding myolysis / rhabdomyolysis complicated with a systemic bacterial infection and the accumulation of muscle damage\nthe non - bacteremic mechanism includes alterations of systemic metabolism ( i.e. , hypoxia , acidosis ) and an intracellular metabolism in situ ( e.g. , disturbances of glycolysis and oxidation in muscle cells ) ( 7 ) .\nthe non - bacteremic mechanism of rhabdomyolysis accompanied by systemic infection is similar , regardless of the pathogen that is involved ( 3,7 ) .\nthe common mechanisms underlying muscle damage arise from a combination of hypoxia , dehydration , and acidemia in the tissue ( 4 ) . in general , rhabdomyolysis develops during the course of systemic infection in up to 5% of bacterial and viral cases ( 7 ) .\nrhabdomyolysis is a specific term describing the excess leakage of enzymes derived from muscular tissue , which can result in multi - organ failure . in our patient , the apparent infection focus was not identified by repeated systemic ct .\nthis negative finding caused a delay in our differentiation of the cause of the patient 's rhabdomyolysis .\nwe treated the patient with meropenem , to which the causative pathogen , m. morganii , is sensitive ; however , an adequate antimicrobial therapy can not always rescue a patient from advanced multiple - organ deterioration .\nrhabdomyolysis should thus be recognized as a more aggressive clinical situation than local myolysis , and one that requires intensive care .\nfurthermore , non - specific myolysis / rhabdomyolysis can occur due to any pathogen ( 7 ) ; thus , it may be underdiagnosed during the infection .\nmyalgia and scant laboratory signs of myolysis / rhabdomyolysis ( usually appearing as liver damage in laboratory data ) can be misdiagnosed in patients with the overlapping leakage of transaminases due to various etiologies .\nclinicians should keep in mind that abnormal liver function test results may be linked to a muscular problem .\nclinicians should be aware of the possibility of systemic infection - associated myolysis / rhabdomyolysis and closely observe immunocompromised patients .\nthis is the first report of lethal rhabdomyolysis caused by m. morganii as a complication in a non - hiv patient .\nshort description : fatal rhabdomyolysis caused by m. morganii can occur in a multiple myeloma patient without hiv .", "answer": "a 64-year - old japanese man with multiple myeloma was admitted to our institute due to fever and hypotension . \n he had received multiple courses of chemotherapy just before his febrile episode . \n blood culturing detected morganella morganii . at the time of the diagnosis , \n his laboratory findings revealed massive rhabdomyolysis with a significantly increased creatinine kinase level ( ck ; 3,582 u / l ) ; 98.8% of which corresponded to the ck - mb isotype . \n we diagnosed the patient with sepsis caused by m. morganii , complicated with severe rhabdomyolysis . \n he died of multi - organ failure 2 days later . \n clinicians should closely observe patients with possible systemic infection - associated rhabdomyolysis .", "id": 996} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe study group comprised 15 patients of both sexes , with age ranging from 13 to 65 years , attending the outpatient department . only those periapical lesions which appeared as radiolucent on the radiographs were included in the study group .\nthose periapical lesions which appeared as radiopaque on the radiographs were eliminated from the study group .\nall the subjects underwent ultrasonographic examination using ge logic 400 mr3 color doppler machine having multifrequency linear transducer using 711 mhz frequency at sheethal diagnostics , davangere , india .\nall the examinations including real - time and color doppler imaging were performed in the periapical area extraorally .\nthe ultrasonographic images were analyzed based on the following principles : \n cystic lesion : a hypoechoic well - contoured cavity surrounded by reinforced bone walls , filled with fluid , and with no evidence of internal vascularization on color doppler examination.granuloma : a poorly defined hypoechoic area , showing rich vascular supply on color doppler examination.mixed lesion : predominantly hypoechoic area with focal anechoic area , showing vascularity in some areas on color doppler examination . \n \ncystic lesion : a hypoechoic well - contoured cavity surrounded by reinforced bone walls , filled with fluid , and with no evidence of internal vascularization on color doppler examination .\ngranuloma : a poorly defined hypoechoic area , showing rich vascular supply on color doppler examination .\nmixed lesion : predominantly hypoechoic area with focal anechoic area , showing vascularity in some areas on color doppler examination .\nthe results of ultrasound were correlated with radiographic and histological findings and were statistically analyzed .\nall the subjects underwent ultrasonographic examination using ge logic 400 mr3 color doppler machine having multifrequency linear transducer using 711 mhz frequency at sheethal diagnostics , davangere , india .\nall the examinations including real - time and color doppler imaging were performed in the periapical area extraorally .\nthe ultrasonographic images were analyzed based on the following principles : \n cystic lesion : a hypoechoic well - contoured cavity surrounded by reinforced bone walls , filled with fluid , and with no evidence of internal vascularization on color doppler examination.granuloma : a poorly defined hypoechoic area , showing rich vascular supply on color doppler examination.mixed lesion : predominantly hypoechoic area with focal anechoic area , showing vascularity in some areas on color doppler examination . \n \ncystic lesion : a hypoechoic well - contoured cavity surrounded by reinforced bone walls , filled with fluid , and with no evidence of internal vascularization on color doppler examination .\ngranuloma : a poorly defined hypoechoic area , showing rich vascular supply on color doppler examination .\nmixed lesion : predominantly hypoechoic area with focal anechoic area , showing vascularity in some areas on color doppler examination .\nthe results of ultrasound were correlated with radiographic and histological findings and were statistically analyzed .\nout of the 15 subjects , 12 ( 80% ) were diagnosed as periapical cyst ultrasonographically , whereas 14 ( 93.3% ) were diagnosed as periapical cyst histopathologically and the correlation between ultrasonographic and histopathologic diagnoses was found to be in 12 ( 85.7% ) subjects [ table 1 and graph 1 ] .\ncorrelation of histologic features with ultrasonographic findings correlation of histologic features with ultrasonographic findings out of the 15 subjects , 2 ( 13.3% ) were diagnosed as periapical granuloma ultrasonographically , whereas 1 ( 6.7% ) was diagnosed as periapical granuloma histopathologically and the correlation between ultrasonographic and histopathologic diagnoses was found to be in 1 ( 50% ) subject . out of the 15 subjects , 1 ( 6.7% ) was diagnosed as periapical abscess ultrasonographically , whereas no subjects were diagnosed as periapical abscess histopathologically and there was no correlation between ultrasonographic and histopathologic diagnoses in this subject .\nthe correlation between histopathologic and ultrasonographic diagnoses was found to be in 13 ( 86.7% ) subjects . comparing the results of ultrasonography with the histopathologic features , the sensitivity , specificity , positive predictive value , and negative predictive value of ultrasonography to diagnose periapical lesions were calculated . in our study\n, tp denotes true positive = 12 subjects , tn denotes true negative = 1 subject , fp refers to false positive = 2 subjects , fn is false negative = 0 subjects , and n is total number of patients = 15 subjects [ table 2 and graph 2 ] .\nout of the 15 subjects , 12 ( 80% ) were diagnosed as periapical cyst ultrasonographically , whereas 14 ( 93.3% ) were diagnosed as periapical cyst histopathologically and the correlation between ultrasonographic and histopathologic diagnoses was found to be in 12 ( 85.7% ) subjects [ table 1 and graph 1 ] .\ncorrelation of histologic features with ultrasonographic findings correlation of histologic features with ultrasonographic findings out of the 15 subjects , 2 ( 13.3% ) were diagnosed as periapical granuloma ultrasonographically , whereas 1 ( 6.7% ) was diagnosed as periapical granuloma histopathologically and the correlation between ultrasonographic and histopathologic diagnoses was found to be in 1 ( 50% ) subject . out of the 15 subjects , 1 ( 6.7% ) was diagnosed as periapical abscess ultrasonographically , whereas no subjects were diagnosed as periapical abscess histopathologically and there was no correlation between ultrasonographic and histopathologic diagnoses in this subject .\nthe correlation between histopathologic and ultrasonographic diagnoses was found to be in 13 ( 86.7% ) subjects .\ncomparing the results of ultrasonography with the histopathologic features , the sensitivity , specificity , positive predictive value , and negative predictive value of ultrasonography to diagnose periapical lesions were calculated . in our study , tp denotes true positive = 12 subjects , tn denotes true negative = 1 subject , fp refers to false positive = 2 subjects , fn is false negative = 0 subjects , and n is total number of patients = 15 subjects [ table 2 and graph 2 ] . diagnostic validity of ultrasonography diagnostic validity of ultrasonography\nout of the 15 subjects in the present study , ultrasonographic examination showed 12 ( 80% ) periapical cysts whereas histopathologic diagnosis revealed 14 ( 93.3% ) periapical cysts .\none of the periapical cysts ( 2 subject ) was misdiagnosed ultrasonographically as periapical granuloma .\nthis misinterpretation was because of the content of the lesion which showed high density equivalent to a solid lesion , even though with lack of vascular supply on color doppler examination .\none of the periapical cysts ( 11 subject ) was misdiagnosed ultrasonographically as periapical abscess [ figure 1 ] .\nthis lesion showed both hypoechoic and anechoic regions , i.e. , mixed echogenic patterns with numerous scattered internal echoes and varying density values within the lesion suggestive of periapical abscess .\nsimilar to our observations , dib et al . in their study of 72 intraosseous lesions of the jaw\nthe reason for this could be due to the presence of thick cortical bone covering the lesion , the occurrence of infected cysts and solid areas within the cystic lesion .\nthe cystic lesions on the ultrasound imaging appeared as anechoic lesion in six cases , turbid fluid in one case , scattered internal echoes in one case , and posterior enhancement in three cases [ figures 2 and 3 ] .\nultrasonograph showing well - defined hypoechoic lesion with vascularity ultrasonograph showing well - defined anechoic lesion ultrasonograph showing well - defined anechoic lesion the internal echoes present in infected cysts and odontogenic keratocyst could be due to dense particles ( cholesterol clefts in the infected cysts ) in the cystic fluid and keratin in odontogenic keratocyst .\nthe density values varied within the lesion in case of infected cysts and odontogenic keratocyst , indicative of difference in the contents within the lesion , which reflects the disease process . out of the 15 subjects in the present study ,\nultrasonographic examination showed 2 ( 13.3% ) periapical granuloma among which 1 ( 50% ) was diagnosed histopathologically as periapical granuloma and the other as periapical cyst .\nthis observation is similar to the observations made by cotti et al . and gundappa et al , where they had accurately diagnosed all the periapical granulomas ( 100% ) ultrasonographically .\nthus , the observations from the present study infer that the diagnostic validity of ultrasonography is similar to that made by dib et al , where they have reported 92.8% accuracy and less compared to that made by cotti et al , and gundappa et al . where they have reported 100% accuracy . in all the subjects ,\nit pictorially represents the anatomic location of the periapical lesion in relation to the particular involved tooth and it provides size of the lesion [ figures 5 and 6 ] , whereas ultrasound was able to accurately identify the underlying disease process reasonably accurately and the size measurements in three dimensions using the ultrasound software .\npanoramic radiograph showing unilocular radiolucent lesion occlusal radiograph showing unilocular radiolucent lesion intraoral periapical radiograph showing radiolucent lesion a major concern over the performance of ultrasonography was the difficulty in attributing the lesions to a specific area of the maxillary bone because the dental landmarks ( i.e. roots ) were not specifically visualized .\nthis made it difficult to orient the lesion in the different regions of the mouth without using a reference radiograph .\nout of the 15 subjects in the present study , ultrasonographic examination showed 12 ( 80% ) periapical cysts whereas histopathologic diagnosis revealed 14 ( 93.3% ) periapical cysts .\none of the periapical cysts ( 2 subject ) was misdiagnosed ultrasonographically as periapical granuloma .\nthis misinterpretation was because of the content of the lesion which showed high density equivalent to a solid lesion , even though with lack of vascular supply on color doppler examination .\none of the periapical cysts ( 11 subject ) was misdiagnosed ultrasonographically as periapical abscess [ figure 1 ] .\nthis lesion showed both hypoechoic and anechoic regions , i.e. , mixed echogenic patterns with numerous scattered internal echoes and varying density values within the lesion suggestive of periapical abscess .\nsimilar to our observations , dib et al . in their study of 72 intraosseous lesions of the jaw\nthe reason for this could be due to the presence of thick cortical bone covering the lesion , the occurrence of infected cysts and solid areas within the cystic lesion .\nthe cystic lesions on the ultrasound imaging appeared as anechoic lesion in six cases , turbid fluid in one case , scattered internal echoes in one case , and posterior enhancement in three cases [ figures 2 and 3 ] .\nultrasonograph showing well - defined hypoechoic lesion with vascularity ultrasonograph showing well - defined anechoic lesion ultrasonograph showing well - defined anechoic lesion the internal echoes present in infected cysts and odontogenic keratocyst could be due to dense particles ( cholesterol clefts in the infected cysts ) in the cystic fluid and keratin in odontogenic keratocyst .\nthe density values varied within the lesion in case of infected cysts and odontogenic keratocyst , indicative of difference in the contents within the lesion , which reflects the disease process . out of the 15 subjects in the present study ,\nultrasonographic examination showed 2 ( 13.3% ) periapical granuloma among which 1 ( 50% ) was diagnosed histopathologically as periapical granuloma and the other as periapical cyst .\nthis observation is similar to the observations made by cotti et al . and gundappa et al , where they had accurately diagnosed all the periapical granulomas ( 100% ) ultrasonographically .\nthus , the observations from the present study infer that the diagnostic validity of ultrasonography is similar to that made by dib et al , where they have reported 92.8% accuracy and less compared to that made by cotti et al , and gundappa et al . where they have reported 100% accuracy .\nin all the subjects , conventional radiography provided the preliminary information about the lesion [ figure 4 ] .\nit pictorially represents the anatomic location of the periapical lesion in relation to the particular involved tooth and it provides size of the lesion [ figures 5 and 6 ] , whereas ultrasound was able to accurately identify the underlying disease process reasonably accurately and the size measurements in three dimensions using the ultrasound software .\npanoramic radiograph showing unilocular radiolucent lesion occlusal radiograph showing unilocular radiolucent lesion intraoral periapical radiograph showing radiolucent lesion a major concern over the performance of ultrasonography was the difficulty in attributing the lesions to a specific area of the maxillary bone because the dental landmarks ( i.e. roots ) were not specifically visualized .\nthis made it difficult to orient the lesion in the different regions of the mouth without using a reference radiograph .\nwith its potential usefulness to differentiate the periapical lesions , ultrasonography can be considered as a better imaging modality with improved efficacy when compared to conventional radiography . in comparision to histopathologic diagnosis ,\nultrasonography showed less accuracy and thus can be considered to be a supplementary tool in the differential diagnosis of periapical lesions .\nfurther research can be directed in larger samples and in different types of periapical lesions to assess the diagnostic validity of ultrasonography .", "answer": "background and objectives : to assess the diagnostic capability of real - time ultrasound imaging , together with the application of color power doppler in the identification and differential diagnosis of the periapical lesions.materials and methods : fifteen patients with periapical lesions of pulpal origin , diagnosed with clinical and conventional radiographic examination , were examined further using ultrasonography . \n the results from the biopsies of the lesions were compared and statistically analyzed.results:the differential diagnosis between periapical granulomas and cystic lesions , which were based on the ultrasonographic findings , were confirmed by the results of the histopathologic examination in 13 ( 86.7% ) of 15 cases , one being granuloma and 14 being cystic lesion.interpretation and conclusion : ultrasound real - time imaging is a technique that may help make a differential diagnosis between cysts and granulomas by revealing the nature of the content of a bony lesion . \n this technique may have further applications in the study of other lesions of the jaws .", "id": 997} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe mucopolysaccharidoses ( mps ) are a family of genetic disorders characterized by changes in an individual s ability to metabolize mucopolysaccharides , which are complex sugar molecules found in the connective tissue , mucosal fluids , synovial fluid , and other cells throughout the body .\nthere are six types of mps , with some types having several subtypes . according to brown ( 1999 ) ,\nepidemiological data are problematic to report , but range from 1 in 100 000 live births to 1 in 600 000 live births .\nthis dysfunction in metabolism may result in a variety of distinct physical features , such as short stature , contracture of joints , claw - like hands , abnormal spine curvature , and hydrocephalus ( neufeld and muenzer 1995 ) .\ntreatment options vary , but hematopoietic cell transplantation seems to offer the best long - term quality of life improvement and decreased mortality and morbidity options for children with some of the more severe forms of mps ( grewal et al 2002 ) .\none subtype of mps is mps i , which includes hurler , scheie , and hurler - scheie syndromes .\neach of these disorders within mps i is caused by a deficiency of alpha - l - iduronidase .\nwithin mps i , hurler syndrome is generally associated with more severe features and poorer prognosis than either scheie or hurler - scheie syndromes ( brown 1999 ) . in most cases of hurler syndrome ,\nmotor skills are limited by age 18 months , and developmental regression occurs , including progressive loss of neurocognitive functioning , resulting in mental retardation . with hurler - scheie syndrome\n, these declines usually appear between 3 and 8 years of age , with milder neurocognitive losses and a low risk for early mortality .\nthese neurocognitive losses typically include progressive dementia resulting from hydrocephalus and increasing deposits of nonmetabolized mucopolysaccharides ( shapiro et al 1995 ) .\nlanguage and memory deficits after a period of initial developmental slowing have been associated with the more severe forms of mps i ( guffon et al 1998 ) . while neurocognitive deficits have been associated with mps , to date\nthere are few neurocognitive reports of children with this disorder and no longitudinal studies , resulting in scant knowledge regarding appropriate assessment and intervention ( brown 1999 )\n. many studies report cross - sectional assessments of these children at different stages . in this case report\n, we have the opportunity to follow a young lady with hurler - scheie syndrome over the course of 10 years , documenting the quantity and quality of neurocognitive effects associated with this disease .\nthis represents a rare chance to longitudinally track the effects of hurler - scheie in a young person and allows recommendations to be made to health care professionals regarding potential neurocognitive and psychological care for children with this disorder .\nresearchers are currently engaging in novel therapies designed to reduce and perhaps reverse the effects of hurler - scheie .\nhowever , while these therapies may have a beneficial effect on orthopedic , skeletal , or ophthalamic problems , their effect on neurocognitive functioning is not clearly understood .\nthus , we are in a position to begin documenting both the physiological and neurocognitive effects of these new treatments .\nthe focus of this case report is to describe long - term neurocognitive changes in a young female with hurler - scheie syndrome that was treated using enzyme replacement therapy . to our knowledge , this is the first longitudinal case report of a patient receiving enzyme replacement therapy for hurler - scheie syndrome .\nthe following information was collected with the approval of the institutional review board at the university of mississippi medical center .\nwe report the case of a now 15-year - old female diagnosed with mps - i , specifically hurler - scheie syndrome , alpha ( not her real name ) .\nalpha s mother gave consent for her child to serve as a subject in this investigation , and alpha gave assent .\nher mother reported alpha grew well at first , but then seemed to slow down . \nher mother also noted alpha could not raise her arms over her head , even as an infant . at age 3.5 years , alpha complained of wrist pain , and was seen by her primary care physician .\nalpha began taking gymnastics class as part of her 4-year - old preschool ; her instructor noted that alpha could not touch her toes or raise her arms .\nalpha was then referred to a local orthopedic clinic and x - rays were obtained . according to alpha s mother ,\nthe clinic noted something wrong on the x - ray films , and referred alpha to a pediatric orthopedic surgeon for further evaluation .\nalpha could not actively abduct her shoulders beyond 90 degrees and passive abduction was limited to 130 degrees .\nshe was noted to have good finger function and grip , and a full range of motion in her neck , hips , knees , ankles , and elbows , with no appreciable organomegaly .\nhowever , after reviewing the x - rays and noting atypical features such as broad ribs with some notching at the medial metaphyseal ends , and smaller than usual femoral heads bilaterally , the orthopedic surgeon suspected alpha had scheie syndrome , one of the mps i syndromes .\nalpha was referred to a geneticist to conduct urine and blood tests and was diagnosed with hurler - scheie syndrome . by age 8 , alpha remained a very happy , bright young lady who was active in theatre camp and swimming ( she used her own , special technique according to her mother ) . she could actively abduct her shoulders 80 degrees and had about 50% range of motion in her neck .\nshe was wearing glasses , was an avid reader , and was doing very well in school . by age 10 in 1999 , alpha was 50 inches ( 124 cm ) tall and weighed 71 pounds ( 32 kg ) .\nshe had restricted range of motion in her hips and knees , and was beginning to complain of neck pain . in 2000 , at the age of 12 , alpha was admitted for the placement of a vp shunt secondary to increasing hydrocephalus .\nshe also began enzyme replacement therapy in 2000 on a pharmaceutical study at the age of 12 , as well as outpatient physical therapy to encourage range of motion in her extremities .\ntanner staging was noted as appropriate for her age ; in general , hurler - scheie and scheie patients have normal puberty and reproductive abilities .\nher neurocognitive functioning was assessed three times , in june 1994 when she was 5 years 11 months old , in june 2002 when she was 13 years 11 months old , and in july 2003 , when she was 15 years old .\nthe initial assessment at age 511 was not conducted by the authors , but took place at another location . however ,\nthis assessment was done by a licensed clinical psychologist who used age - appropriate , valid measures .\ncopies of the report from that assessment were reviewed from the patient s medical chart .\ngiven her young age ( 511 ) at her initial assessment , the patient was administered the stanford - binet intelligence scale , fourth edition , and the wide range achievement test , third edition ( see table 1 ) .\nthese measures assess for intelligence ( iq ) and achievement , respectively . at the time\n, the patient had just completed kindergarten , had no behavior problems , and was considered by her teachers to be ready for the first grade .\nher mother likewise thought the patient was doing well academically , but was concerned that the patient could perhaps have been showing signs of mild forgetfulness .\noverall , the scores on these measures range from the average to the highly superior range , as she scored at or above the 90th percentile in most areas . at that time , it was clear that alpha was functioning in the average to superior range intellectually and academically , and had no significant behavioral or emotional problems .\nalpha s parents were aware of the impressive nature of these findings , but were also aware of the usual course of this disease , including gradual neurocognitive decline .\nthey began both systematic and non - specific interventions designed to challenge alpha intellectually and stimulate her already significant cognitive abilities .\nalpha was enrolled in a school that stressed academic excellence , and her mother reported that alpha did well through the seventh grade .\nalpha was home - schooled for the second half of the seventh grade , as she was travelling frequently to receive treatment for her condition .\nwhen she began eighth grade back at her same school , her grades began to fall from consistent as up through the seventh grade to bs and cs in the eighth grade .\nthis prompted alpha s parents to seek another neurocognitive evaluation . at the time of the second assessment , the patient was 13 years and 11 months , and\nthis second battery consisted of parts of the wechsler intelligence scale for children third edition ( wisc - iii ) , woodcock - johnson tests of cognitive ability third edition ( wj - iii ) , the wide range assessment of memory and learning ( wraml ) , the california verbal learning test \nchildren s version ( cvlt - c ) , the stroop color and word test , the rey - osterrieth complex figure test ( rocf ) , the child behavior checklist ( cbcl - parent report ) , the youth self report ( ysr ) , the children s depression inventory ( cdi ) , and the revised children s anxiety and depression scale ( rcads ) .\nthis battery is designed to be a comprehensive measure of intelligence , neurocognitive functioning , and behavioral and emotional adjustment .\nit should be noted that though different batteries of measures were used between neurocognitive assessments , the results from both assessments are comparable .\nspecifically , overall intelligence quotient ( iq ) scores between the stanford - binet and the woodcock - johnson show good correlation ( sattler 1992 ) . results from this second assessment indicate a significant decline in overall abilities from alpha s initial level of functioning . her abilities were now within the average range of functioning ; however , she again demonstrated no significant behavioral or emotional problems .\nalpha s parents began implementing suggested interventions , including after school tutoring and structuring alpha s study time so that she studied for short blocks of time with frequent breaks . at the time of this report\n, alpha s mother described alpha as doing better in school ( generally bs and cs , a few as ) , and continuing to be emotionally and socially well - adjusted .\nshe completed the same battery as the one she completed at age 1311 ( see table 3 ) .\nwhile declines in neurocognitive functioning are generally expected in children with mps , this case report of a young lady with hurler - scheie demonstrates that declines may proceed at different rates and are likely influenced by premorbid neurocognitive functioning and environmental behavioral vectors . in other words ,\nalpha s current level of average neurocognitive functioning is probably the result of impressive capabilities prior to the onset of hurler s syndrome as well as the degree of intervention and cognitive expectations that characterize her family system .\nthe idea of cognitive reserve as a protective factor in individuals who have some sort of neurological insult has been assumed in children with traumatic brain injury and brain tumors .\nthus , it could be that since alpha had such a high premorbid level of functioning , she had more to spare during the course of her illness and treatment ( taylor 2004 ) .\nit should be noted that many children with hurler - scheie show some degree of cognitive sparing , in comparison with other types of mps .\nit should be noted that alpha has been diagnosed with a milder form of mps , hurler - scheie , and that this subtype of mps has been shown to involve relative neurocognitive sparing ( brown 1999 ) .\nhowever , this report is the first of its kind to our knowledge to document longitudinal changes in a youngster .\nthe issue of alpha s current level of neurocognitive functioning can not be fully addressed in this report .\nher initial decline is undoubtedly related to her diagnosis of hurler - scheie syndrome . however , the amount of decline and conversely the degree of neurocognitive sparing attributable to her premorbid functioning and behavioral interventions by her parents is indeterminable .\nthe differences in her test performance may be attributable to regression to the mean , a common result of multiple assessments conducted on a single individual .\nconsequently , we can not estimate the amount of variance accounted for by alpha s premorbid intellectual capabilities , hurler - scheie syndrome , and her parents level of cognitive and intellectual interventions .\nit should also be noted that the measured decline in iq might be related to progressive motor dysfunction , as this might affect some of the subtests on the neurocognitive measures .\nthere are no reports of the possible neurocognitive - sparing or improving effects of enzyme replacement therapy , which alpha received .\nweaknesses of this case report include the use of different measures of intelligence and neurocognitive functioning .\nhowever , all measures used to assess this patient are well - established , well - validated measures , and hence should be interpreted as adequately reflecting her level of neurocognitive functioning at the time they were administered .\nthis case represents a unique opportunity to study a genetic disorder with neurocognitive effects , in the light of apparently strong biological and environmental protective factors .\nchildren with hurler - scheie syndrome should be followed regularly with neurocognitive assessments in order both to document expected intellectual declines and to target areas for cognitive and behavioral interventions that might slow the decline associated with this disease .\nthe strong behavioral and environmental support that alpha received from her parents can not be discounted .\nalpha s parents proactively began working with her in light of her diagnosis , and then followed through with a neurocognitive rehabilitation plan suggested by the first author ( tde ) .\nthis neurocognitive rehabilitation plan was tailored to address the specific levels of functioning that alpha evidenced from her assessments .\nwe strongly recommend neurocognitive assessment and intervention for these patients , alongside newer medical interventions .\nthe lack of continued neurocognitive decline from age 1311 to age 150 may be attributable to ( 1 ) the milder form of mps with which alpha was diagnosed , ( 2 ) the newer treatments initiated by the team of physicians ( jm ) , ( 3 ) the fact that alpha probably began life with a higher - than - average neurocognitive capacity , or ( 4 ) the supportive and appropriately challenging environment of social support that alpha enjoyed .\nhowever , neurocognitive assessment adds a low burden to an overall treatment plan , and can help with behavioral interventions designed to improve long - term neurocognitive functioning .", "answer": "an adolescent with hurler - scheie syndrome is reported . \n this now 15 year - old - young woman was initially diagnosed at age 4 . \n she was assessed for neurocognitive functioning at ages 5 , 13 , and 15 years . \n results show a significant decline in intellectual functioning from the superior range to the average range from age 5 to age 13 , and then no change from age 13 to age 15 . \n the relationship between hurler - scheie syndrome , premorbid intellectual functioning , and cognitive behavioral interventions are discussed in light of the longitudinal neurocognitive effects of this disease .", "id": 998} {"query": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ntransesophageal echocardiogram ( tee ) has been introduced to the operating room over 30 years ago .\nwe report a case of esophageal perforation caused by tee during an aortic valve replacement operation , treated successfully with a new endoscopic clip . to the best of our knowledge ,\nthis is the first case of post - tee esophageal perforation treated endoscopically with this new clip device .\na 72-year - old female was admitted to the operating theater for aortic valve replacement . during the operation and in the first hours in the intensive care unit ( icu )\nthe patient had to undergo tee in order to assess postoperative left ventricle performance status .\na deep 2 1.5 cm ulcer covered with blood thrombus was found approximately 2 cm above the gastroesophageal junction .\nthe rest of the endoscopy was unremarkable . within the next 48 h , thoracic and\nonly a few blood clots were found in the area between the stomach and the left liver hilum , but no signs of mediastinitis or free intra - abdominal air .\nfour days later , as the patient became febrile , a second gastroscopy was performed .\na 2 1.5 cm perforation was seen at the same site of ulcer with no bleeding ( fig .\ndue to the patient 's clinical condition and the size of the gap , an endoscopic intervention was decided . a new 12-mm clip ( otsc ; ovesco endoscopy , tbingen , germany ) was engaged .\nthe clip is made of nitinol and approximates large perforation margins like a surgical clamp .\nthe edges of the perforation were approximated by using a specific endoscopic double grasping forceps and applying suction through the cap .\nthus , the tissue was pulled into the cap and the clip was released by rotating the wheel attached to the shaft of the endoscope .\na nasogastric levin tube was uneventfully left in the stomach under direct vision for long - term enteral feeding .\nfurther , the patient was offered two intra - abdominal drainage catheters in the operating theater so that intra - abdominal air and blood clots be drained and high fever get under control .\nall intra - abdominal and peripheral blood cultures were sterile . the patient was kept on intravenous antibiotics , proton pump inhibitors and parenteral nutrition over the next 10 days followed by enteral feeding through the levin tube .\ntwo weeks later she was transferred to the clinical ward , experiencing no dysphagia , and was discharged fully recovered 3 months after the operation .\ntee has safely been applied in patients undergoing cardiac surgery and in icu departments for diagnostic purposes and monitoring over 30 years .\nfactors that may determine the way of intervention following esophageal perforation are age , clinical condition , location and size of the perforation , cost of intervention and elapsed time since the injury .\nthe time since perforation has occurred is crucial . a diagnosis delayed for more than 36\nh is associated with high mortality ( 50% ) , despite surgical intervention . up to date , there have been no randomized controlled trials comparing surgical to endoscopic intervention regarding patient outcome . in our case ,\nthe tee performed in the operating theater and the icu led to esophageal perforation due to the patient 's esophagus anatomy .\nthe delayed diagnosis of perforation is attributed to the blood thrombus on top of the ulcer seen in the first endoscopy that behaved as a sealant .\nour patient 's serious clinical condition precluded major surgical intervention , and it was decided to provide her with endoscopic therapy .\nadditionally , due to the size of perforation and cost , a single clip that could seal the gap was very appealing .\nlast , by leaving this clip in place for a long time , longer than common clips , could possibly guarantee safe sealing of this perforation . according to clip manufacturers ,\nthe clip may remain in place for over 6 months and is magnetic resonance imaging - safe .\nesophageal perforations closed endoscopically range from 3 to 25 mm in size . due to the new device technology ( twin grasper and the cap at the tip of endoscope ) , a single clip is enough and able to create a full - thickness closure of perforations up to 3 cm in diameter .\nthis new clip provides a secure and successful esophageal perforation closure rate , up to 100% in perforations diagnosed within the first 24 h . according to this study , the clip remains in place for over 6 months and\nthe mean repairing time of an esophageal perforation after successful multiple clipping is 18 days ( interquartile range 626 ) .\nmost importantly , chronicity of perforation ( > 10 days ) was the only independent predictive factor for successful perforation closure in univariate and multivariate analysis .\nhowever , esophageal perforation as a complication of this clip during patient intubation has been reported in up to 3% of patients , but probably this can be attributed to the learning curve .\nindeed , in another study with 94 patients regarding the use of the otsc clip to narrow the pouch in patients who underwent gastric bypass surgery , no esophageal perforation occurred . in conclusion\n, although tee is a safe procedure , it may be complicated by esophageal perforation .\nwe clearly showed and strongly suggest that esophageal perforation of 5 days can safely and successfully be treated endoscopically by applying this new otsc clip device .", "answer": "esophageal perforation due to transesophageal echocardiogram ( tee ) during cardiac surgery is rare . \n a 72-year - old female underwent tee during an operation for aortic valve replacement . \n further , the patient presented hematemesis . \n gastroscopy revealed an esophageal bleeding ulcer . \n endoscopic therapy was successful . \n although a ct scan excluded perforation , the patient became febrile , and a second gastroscopy revealed a big perforation at the site of ulcer . \n the patient 's clinical condition required endoscopic intervention with a new otsc clip ( ovesco endoscopy , tbingen , germany ) . the perforation was successfully sealed . \n the patient remained on intravenous antibiotics , proton pump inhibitors and parenteral nutrition for few days , followed by enteral feeding . \n she was discharged fully recovered 3 months later . \n we clearly demonstrate an effective , less invasive treatment of an esophageal perforation with a new endoscopic clip .", "id": 999}